PMID- 20284644 TI - The tuberculosis service. PMID- 20284646 TI - PASSING of UNRRA. PMID- 20284645 TI - Ten years of premarital blood test law. PMID- 20284647 TI - STREPTOMYCIN. PMID- 20284648 TI - The varieties of fungi causing ringworm of the scalp. PMID- 20284649 TI - OLD people. PMID- 20284650 TI - TUBERCULOSIS in Newfoundland. PMID- 20284651 TI - Food rations for invalids. PMID- 20284653 TI - Part-time nursing scheme for county infirmaries. PMID- 20284652 TI - Problem families. PMID- 20284654 TI - Scabies in the sub-tropics. PMID- 20284655 TI - Observations on the etiology and frequency of spondylolisthesis and its precursors. PMID- 20284656 TI - Roentgen features of mucocele of the appendix. PMID- 20284657 TI - Roentgen treatment of infections of the tonsils and post-pharyngeal lymphoid tissues in children. PMID- 20284658 TI - Fractures following electroshock therapy. PMID- 20284659 TI - Cardiac enlargement. PMID- 20284660 TI - Benign ulceration within a duodenal diverticulum; report of a case. PMID- 20284661 TI - Reactions of connective tissues after protracted fractional irradiation of laryngeal carcinoma. PMID- 20284662 TI - The biological significance of fibrinous radiomucositis of the larynx. PMID- 20284663 TI - Latex cap for radon ointment treatment. PMID- 20284664 TI - Retroperitoneal perforation of the duodenum; report of a case. PMID- 20284665 TI - Carcinoma of the transverse colon in a 15-year-old boy; case report with short summary of the literature. PMID- 20284666 TI - Some practical aspects of hip nailing. PMID- 20284667 TI - Application of the inverse-square law to oil-immersed tubes. PMID- 20284669 TI - Thoracic surgery in a hospital center. PMID- 20284673 TI - Streptomycin in surgical infections; laboratory studies. PMID- 20284678 TI - Large melena caused by sponge ulcerating into lumen of ileum more than twenty years after celiotomy. PMID- 20284679 TI - Perforated carcinoma of the large intestine complicating pregnancy; successful operative management. PMID- 20284680 TI - Education and certification of orthopaedic surgeons in the United States. PMID- 20284681 TI - Survival in bone sarcoma. PMID- 20284682 TI - Complications of fractures of the neck of the femur. PMID- 20284683 TI - The pathology of ununited fractures of the neck of the femur. PMID- 20284684 TI - Complications of old fractures of the neck of the femur; results of treatment of vitallium-mold arthroplasty. PMID- 20284685 TI - Painful, non-suppurative, localized sclerosis of long bones; with a report of two cases. PMID- 20284686 TI - The newer pathological and physiological concepts of anterior poliomyelitis and their clinical interpretation. PMID- 20284687 TI - The diagnosis of meniscus injuries; some new clinical methods. PMID- 20284688 TI - Muscle fibrodystrophy; a syndrome causing chronic physical disability. PMID- 20284689 TI - Pseudarthrosis of the long bones. PMID- 20284690 TI - Fracture-dislocation of the thoracolumbar spine; with special reference to reduction by open and closed operations. PMID- 20284691 TI - Osteotomy-osteoclasis; a method for correcting long-bone deformities. PMID- 20284692 TI - Fracture-dislocation of the ankle with fixed displacement of the fibula behind the tibia. PMID- 20284693 TI - The formation and significance of vertebral ankylosis in tuberculous spines. PMID- 20284694 TI - Primary congenital subluxation of the hip. PMID- 20284695 TI - The use of parallel grafts and of two-stage and three-stage interlocking grafts in the treatment of idiopathic scoliosis. PMID- 20284696 TI - Vitamin-A deficiency and excess in relation to skeletal growth. PMID- 20284697 TI - Mobilization of metacarpophalangeal joints; arthroplasty and capsulotomy. PMID- 20284698 TI - The definition of human locomotion on the basis of measurement; with description of oscillographic method. PMID- 20284699 TI - Pre-employment examinations of the back. PMID- 20284700 TI - An improved skin-traction technique for the fingers. PMID- 20284701 TI - Infantile cortical hyperostosis. PMID- 20284702 TI - Osteomyelitis caused by Salmonella typhimurium. PMID- 20284703 TI - Salmonella infection involving the knee joint; report of a case. PMID- 20284704 TI - Ununited epiphysis of the ischium; report of a case. PMID- 20284705 TI - Ossifications associated with chronic strain of the tibial collateral ligament from roller-skating. PMID- 20284706 TI - An efficient dual-purpose retractor. PMID- 20284707 TI - A miniature galvanic stimulator. PMID- 20284708 TI - An improved retractor for intervertebral-disc surgery. PMID- 20284709 TI - Modification of the Denis Browne splint. PMID- 20284710 TI - Modification of cast spreader. PMID- 20284711 TI - A review of the evolution of the orthopaedic branch of surgery in New York City. PMID- 20284712 TI - Rehabilitation of the arm amputee. PMID- 20284713 TI - Tubed pedicle complications in repair of massive tissue defects. PMID- 20284714 TI - Surgical technique helpful in obtaining fine scars. PMID- 20284715 TI - Implantation of fascial strips through the masseter muscle for surgical correction of facial paralysis; a report of 11 cases. PMID- 20284716 TI - The correction of some forms of acquired ptosis. PMID- 20284717 TI - Tattooing of corneal scars with insoluble pigments. PMID- 20284718 TI - Coloboma of the eyelids. PMID- 20284719 TI - Reconstruction of the nasal septum. PMID- 20284720 TI - The role of the platysma muscle in torticollis deformity. PMID- 20284721 TI - Anastomosis between the ureter and urinary bladder by means of a subcutaneous skin tube. PMID- 20284722 TI - Reconstruction of the columella. PMID- 20284723 TI - Inking pens for skin marking in plastic surgery. PMID- 20284724 TI - Malignant melanoma in the Negro; with report of six cases. PMID- 20284725 TI - Uterine bleeding; puberty, maturity, post climacteric. PMID- 20284726 TI - Primary neoplasms of the trachea. PMID- 20284727 TI - Carcinoma of the prostate gland. PMID- 20284728 TI - Recent advances in ophthalmic surgery. PMID- 20284729 TI - The problem for the anesthesiologist in dealing with the malnourished patient. PMID- 20284730 TI - Fundamentals in surgical preparation of thyrotoxic patients; use of thiouracil. PMID- 20284731 TI - Parenteral fluids. PMID- 20284732 TI - Lipoma of the colon; treated by primary resection, with end-to-end anastomosis. PMID- 20284733 TI - Repair of inguinal hernia with whole skin grafts. PMID- 20284734 TI - Intracranial aneurysms: considerations in surgical management. PMID- 20284735 TI - Mediastinal cysts; report of a case. PMID- 20284736 TI - Internal biliary fistulas; report of a case. PMID- 20284737 TI - Carotid body tumor. PMID- 20284738 TI - The Blalock operation for congenital pulmonic stenosis; report of two successful cases. PMID- 20284739 TI - Retroperitoneal chylous cyst. PMID- 20284740 TI - Modern management of peripheral vascular diseases. PMID- 20284741 TI - Volvulus neonatorum. PMID- 20284742 TI - Management of diseases of the pancreas. PMID- 20284743 TI - Carcinoma of the breast. PMID- 20284744 TI - The parathyroid problem. PMID- 20284745 TI - Acute intussusception in infants and children; an analysis of 95 cases in the Cook County Children's Hospital. PMID- 20284746 TI - Suppurative cholangitis. PMID- 20284747 TI - Laboratory diagnosis and its pitfalls in the management of surgical jaundice. PMID- 20284748 TI - Intestinal obstruction; analysis of 352 cases. PMID- 20284749 TI - Bowel obstruction in the newborn. PMID- 20284750 TI - Acute abdominal surgery with special reference to bowel obstruction and a note on chronic appendicitis obliterans. PMID- 20284751 TI - Surgical sequelae following recovery from a perforated peptic ulcer. PMID- 20284752 TI - Transabdominal repair of esophageal hiatus hernia. PMID- 20284753 TI - Methods of nerve repair. PMID- 20284754 TI - Trigeminal neuralgia; its relief in the aged and feeble. PMID- 20284755 TI - Sympathectomy in peripheral vascular disease and hypertension. PMID- 20284756 TI - Large nonpulsating hematoma (false aneurysm). PMID- 20284758 TI - Osteomyelitis. PMID- 20284757 TI - Posterior approach to the knee. PMID- 20284759 TI - Nonunion in fractures. PMID- 20284760 TI - Fractures involving the elbow with special reference to the head of the radius and olecranon. PMID- 20284761 TI - The estimation of water and salt requirements in the surgical patient. PMID- 20284762 TI - A new technique for pulmonary segmental resection; its application in the treatment of bronchiectasis. PMID- 20284763 TI - Clinical experiences with the use of penicillin treatment of infections involving bones and joints. PMID- 20284764 TI - Carcinoma of the prostate; review of 130 cases treated between 1940 and 1946. PMID- 20284765 TI - Studies on anuria; effect of infusion fluids and diuretics on the anuria resulting from severe burns. PMID- 20284766 TI - Diverticula of the stomach and duodenum; treatment by invagination and suture. PMID- 20284767 TI - Growth of human trophoblast in eye of rabbit; its relationship to the origin of cancer; a preliminary report. PMID- 20284768 TI - The blood supply of the kidney, suprarenal gland, and associated structures. PMID- 20284769 TI - Simplified repair of the common duct; use of umbrella catheter to produce internal biliary fistula. PMID- 20284770 TI - Unilateral exophthalmos, and early sign in thyrotoxicosis. PMID- 20284771 TI - Thoracicoabdominal approach to the upper abdomen. PMID- 20284772 TI - Histopathology of the anal ducts. PMID- 20284773 TI - Extra-articular repair for ruptured collateral and cruciate ligaments. PMID- 20284774 TI - Anatomic disarticulation of the hip. PMID- 20284775 TI - The advantages and limitations of thiouracil therapy in thyrotoxicosis. PMID- 20284776 TI - Observations on the use of G-11 in the surgical scrub. PMID- 20284777 TI - Plasma fractions; fibrin foam, thrombin, and fraction No. 1, in general surgery. PMID- 20284778 TI - Clinical observations on furacin soluble dressing in the treatment of surface infections. PMID- 20284779 TI - Progress in the surgical treatment of carcinoma of the esophagus. PMID- 20284780 TI - Fractures of the os calcis. PMID- 20284781 TI - The interdependence of artist and anatomist. PMID- 20284782 TI - Experimental appendical peritonitis; the significance of imbalance of circulating fibrinolytic and antifibrinolytic factors in the course of the disease. PMID- 20284783 TI - Coexistent duodenal ulcer and gastric malignancy. PMID- 20284784 TI - The use of streptomycin in surgical patients. PMID- 20284785 TI - 17-Ketosteroids in the diagnosis of adrenal tumors. PMID- 20284786 TI - Retroperitoneal teratoma; successfully removed from a 15 month-old Negro girl. PMID- 20284787 TI - Delayed suture of war wounds. PMID- 20284788 TI - Plasma cell mastitis. PMID- 20284789 TI - Secondary damage in wounding due to pressure changes accompanying the passage of high velocity missiles. PMID- 20284790 TI - The treatment of acute appendicitis superimposing severe exophthalmic goiter. PMID- 20284791 TI - Malignant soft tissue tumors of the lower extremities; a radical-conservative technique of wide excision and skin grafting without amputation; report of five cases. PMID- 20284792 TI - A controlled suction apparatus for general surgical use. PMID- 20284793 TI - Surgery of war wounds of the abdomen; a review of 100 consecutive patients, operated upon by a single surgical team, working in forward areas in the European Theater of Operations. PMID- 20284794 TI - The importance of nonsurgical measures in the treatment of intestinal obstruction. PMID- 20284795 TI - Chronic salpingitis. PMID- 20284796 TI - Primary extrarenal hypernephroma; discussion of sites and origins, and report of a case. PMID- 20284797 TI - Sympus apus; a case report. PMID- 20284798 TI - Exsanguinating hemorrhage in peptic ulcer. PMID- 20284799 TI - Hydrogen ion concentration (pH) of normal vaginas. PMID- 20284800 TI - X-ray irradiation to promote ovulation. PMID- 20284801 TI - The importance of the liver in reproductive physiology. PMID- 20284802 TI - Treatment of azoospermia by vaso-epididymal anastomosis. PMID- 20284803 TI - Recent advances in abdominal surgery. PMID- 20284804 TI - Tropical medicine and the challenge of global war. PMID- 20284805 TI - Tropical medicine and the challenge of global peace. PMID- 20284806 TI - The distribution of exoerythrocytic parasites and the tissue reaction caused by blood-induced Plasmodium gallinaceum infection in chicks. PMID- 20284807 TI - Studies on atabrine (quinacrine) suppression of malaria; the epidemiological significance of atabrine suppression. PMID- 20284808 TI - The transmission of Plasmodium malariae by Anopheles maculipennis freeborni. PMID- 20284809 TI - The diagnosis of Schistosoma mansoni infections; note on the use of a rectal scraper. PMID- 20284810 TI - Results of certain studies on the stomach in Schistosomiasis japonica. PMID- 20284811 TI - Intradermal and complement fixation reactions elicited by various antigens in persons infected with Onchocerca volvulus. PMID- 20284812 TI - Intestinal parasitic infections in naval personnel. PMID- 20284813 TI - DDT dust for the control of head lice. PMID- 20284814 TI - The treatment of Carrion's disease with large transfusions. PMID- 20284815 TI - The evaluation of the surgical treatment of recurrent echinococcic cysts of the liver followed by deep X-ray therapy. PMID- 20284816 TI - Hawaii fights tuberculosis. PMID- 20284817 TI - TB tests in schools; pro and con. PMID- 20284818 TI - What the thoracoplasty patient should know. PMID- 20284819 TI - Sanitation of the air. PMID- 20284820 TI - The tuberculosis specialist; the tuberculologist. PMID- 20284821 TI - Some features of autolytic tuberculin that adapt it for special specific test purposes. PMID- 20284822 TI - Antibiotics in experimental tuberculosis (with special reference to subtilin). PMID- 20284823 TI - A review of the experiments with BCG immunization in Brazil and the beneficial results obtained. PMID- 20284824 TI - Climate and tuberculosis. PMID- 20284825 TI - The health card and the Abreu X-ray method as used in Asuncion, Paraguay. PMID- 20284826 TI - Lupus vulgaris; report of a case of five years' standing, satisfactorily treated with diasone. PMID- 20284827 TI - Gunshot wounds of the ureter; three cases, with preservation of the kidney in two. PMID- 20284828 TI - Physiological variations in pyelograms commonly interpreted as pathological; a revised standard of normality, with special reference to the cystoid theory. PMID- 20284829 TI - Urethro-trigonitis in relation to abacterial pyuria. PMID- 20284830 TI - The endoscopic treatment of urethrotrigonitis in women. PMID- 20284831 TI - The hormonal therapy of vesical carcinoma. PMID- 20284832 TI - The use of streptomycin in the treatment of urinary tract infections. PMID- 20284833 TI - Some observations on litholapaxy. PMID- 20284834 TI - Cystoscopy of vesical papilloma; is the diagnosis of benignity possible? PMID- 20284835 TI - When is resection completed? PMID- 20284836 TI - Vesical neck obstruction caused by leukemia; case report. PMID- 20284837 TI - Transurethral treatment of vesical neoplasms. PMID- 20284838 TI - Instrumental repair at the bladder neck. PMID- 20284839 TI - Stricture formation following transurethral resection; its prevention and treatment. PMID- 20284840 TI - Urinary incontinence following suprapubic prostatectomy; with report of three cases. PMID- 20284841 TI - Primary tumor of the ureter. PMID- 20284842 TI - Polycystic disease of kidneys causing dystocia; review of the literature and report of a case. PMID- 20284843 TI - Endoscopic exploration of the membraneous urethra. PMID- 20284844 TI - The clinic for the treatment of syphilitics. PMID- 20284845 TI - An unusual foreign body in the urethra and bladder; case report. PMID- 20284847 TI - Lymphogranuloma venereum. PMID- 20284846 TI - Three cases of acute nephritis treated with vitamin E. PMID- 20284848 TI - A bean as a nucleus in a vesical calculus. PMID- 20284849 TI - Birth of penicillin. PMID- 20284850 TI - Administration of penicillin. PMID- 20284851 TI - Penicillin therapy of early syphilis in 14,000 patients. PMID- 20284852 TI - The evolution of the Huhner test. PMID- 20284853 TI - Rapid treatment of early syphilis with penicillin in beeswax and oil. PMID- 20284854 TI - Prenatal syphilis; report of two families. PMID- 20284855 TI - The Herxheimer reactions of relatively small doses of penicillin. PMID- 20284856 TI - The chemotherapy of calf pneumonia; some pharmacologic aspects of sulfonamide administration to normal calves. PMID- 20284857 TI - The chemotherapy of calf pneumonia; the use of sulfathiazole, sulfapyridine, and sulfadiazine in the treatment of calf pneumonia. PMID- 20284858 TI - The genesis of bovine udder infection and mastitis; the occurrence of streptococcal infection in a cow population during a seven-year period and its relationship to age. PMID- 20284860 TI - Submucosal glands in the bovine ileum. PMID- 20284859 TI - Infection of the bovine udder with yeastlike fungi. PMID- 20284861 TI - Vaccination studies on bovine trichomoniasis. PMID- 20284862 TI - Some experimental investigations on the etiology of leucemia in cattle. PMID- 20284863 TI - Length of gestation in range sheep. PMID- 20284864 TI - Studies on baby pig mortality; chemistry of the blood during fasting and refeeding of weanling pigs. PMID- 20284865 TI - The behavior of the peripheral blood elements in panleucopenia (agranulocytosis) of the domestic cat. PMID- 20284866 TI - Chicken embryo vaccine against Newcastle disease (pneumoencephalitis). PMID- 20284867 TI - Studies in avian leucosis; the transmissibility of visceral lymphomatosis. PMID- 20284868 TI - Studies in avian leucosis; the use of biopsy technique in the study of visceral lymphomatosis. PMID- 20284869 TI - Adsorbate Newcastle disease (avian pest) vaccine. PMID- 20284870 TI - Immunity and cross immunity reactions obtained with several avian lymphoid tumor strains. PMID- 20284871 TI - Isolation of Shigella gallinarum from turkey eggs. PMID- 20284872 TI - Transmission of the virus of Newcastle disease to the Syrian hamster. PMID- 20284873 TI - Infection and transmission of Brucella by ectoparasites. PMID- 20284874 TI - International veterinary congresses. PMID- 20284875 TI - Early septicaemia in anthrax. PMID- 20284876 TI - So-called skin tuberculosis. PMID- 20284877 TI - Comparative differential leucocytic counts in tuberculin positive animals and clinical cases of tuberculosis. PMID- 20284878 TI - Rinderpest in Rajputana. PMID- 20284879 TI - Augmenting milk production. PMID- 20284881 TI - An undiagnosed disease among ponies in the Nilgiris District. PMID- 20284880 TI - Rinderpest control; impressions of a field worker. PMID- 20284882 TI - Sulphanilamide in bovine practice. PMID- 20284883 TI - Cases of hypocalcaemia? PMID- 20284884 TI - Incidence of Babesia motasia in a lamb. PMID- 20284885 TI - Castration of pigs. PMID- 20284886 TI - Malicious poisoning of cattle by Calotropis gigenta. PMID- 20284887 TI - Observations on the distribution of disease, including neoplastic disease of the generative, urinary and locomotory systems of the domesticated animals. PMID- 20284888 TI - An outline on genetic factors. PMID- 20284889 TI - The occurrence of contagious caprine pleuro-pneumonia in Assam. PMID- 20284890 TI - Rinderpest and its control in the Province of Bombay. PMID- 20284891 TI - Rinderpest in Tanjore District (Madras Presidency). PMID- 20284892 TI - A note on glycosuria in rabies. PMID- 20284893 TI - A myxofibroma in the heart of a goat. PMID- 20284894 TI - Retention of placenta; a safe technique for its treatment. PMID- 20284895 TI - Equine and bovine surra; its incidence in Baroda State during the year 1944 and 1945. PMID- 20284896 TI - Prevalent diseases of race horses in Egypt; conclusion of 1927-1947 observations. PMID- 20284897 TI - Treatment of mastitis in dairy cows with penicillin. PMID- 20284898 TI - VETERINARY service for the K-9 corps. PMID- 20284900 TI - SWINE parasites and parasitisms. PMID- 20284899 TI - PHARMACEUTICAL by-products of meat animals. PMID- 20284901 TI - Effect on feline growth of heat-processed foods and metabolized vitamin D milk. PMID- 20284902 TI - Unusual boar castration. PMID- 20284903 TI - Rabies with atypical course and symptoms. PMID- 20284904 TI - Necrobacillosis in a steer. PMID- 20284905 TI - Veterinary practice; surgery. PMID- 20284906 TI - Mitotic activity in the anterior hypophysis of ovariectomized rats after injection of estrogens. PMID- 20284907 TI - Mechanics of invagination. PMID- 20284908 TI - Limb ablation experiments on the embryonic chick and its effect as observed on the mature nervous system. PMID- 20284909 TI - Studies on the ligaments of the oviduct in the domestic fowl. PMID- 20284910 TI - The costomediastinal border of the left pleura in the precordial area. PMID- 20284911 TI - Chromaffin patterns in bird adrenals. PMID- 20284912 TI - The mammary gland development in male mice at nine weeks of age. PMID- 20284913 TI - The accessory reproductive glands of Parascalops with notes on homologies. PMID- 20284914 TI - A study of the amnion with the electron microscope. PMID- 20284915 TI - The general pharmacologic action of a new vasopressor drug, EA-83 (2-methylamino 6-hydroxy-6-methyl heptane, 2 methylamino iso-octanol). PMID- 20284916 TI - Comparison of the pharmacologic properties of some new analgesic substances. PMID- 20284917 TI - Early clinical experience with dolophine (No.10820). PMID- 20284918 TI - Effects of vitamin C deficiency and starvation upon the toxicity of procaine. PMID- 20284919 TI - Complications of spinal anesthesia. PMID- 20284920 TI - Multiple-dosage curare technique anesthesia. PMID- 20284921 TI - Apparent decerebrate rigidity and recovery; a case report. PMID- 20284923 TI - The beginning of civilization in America. PMID- 20284922 TI - The laboratory dog [the vivisection controversy]. PMID- 20284924 TI - Primitive surgery. PMID- 20284925 TI - Tarascan political geography. PMID- 20284926 TI - Bifurcate merging, a test of five theories. PMID- 20284927 TI - On the implications for anthropology of the Gesell-Ilg approach to maturation. PMID- 20284928 TI - Evolution, social or cultural? PMID- 20284929 TI - Anthropology for the common man. PMID- 20284930 TI - Status and function as factors in the structure of organizations among the Japanese. PMID- 20284931 TI - Anthropology during the war; India. PMID- 20284932 TI - The significance and applications of bacteriophage in bacteriological and virus research. PMID- 20284933 TI - The mosquitoes of Bwamba County, Uganda; the vertical distribution and biting cycle of mosquitoes in rain-forest, with further observations on microclimate. PMID- 20284934 TI - The habits and control of the red locust in outbreak areas and elsewhere. PMID- 20284935 TI - Breeding the house-fly (Musca domestica, L.) in the laboratory; introduction and technique. PMID- 20284936 TI - Cotton stainers (Dysdercus spp.) in the West Indies. PMID- 20284937 TI - Factors influencing the interaction of insecticidal mists and flying insects; some experiments with adjuvants. PMID- 20284938 TI - Initial experiments in the use of DDT against mosquitoes in British Guiana. PMID- 20284939 TI - An account of a black aphid, Doralis fabae (Scop.) subsp. armata (Hausmann), found on Digitalis purpurea, L. PMID- 20284940 TI - A laboratory comparison of the toxicity as a contact poison of DDT with nicotine, derris products and the pyrethrins. PMID- 20284941 TI - The effect of medium on the toxicity of DDT to aphids. PMID- 20284942 TI - Studies on the nutritional requirements of Brucella suis. PMID- 20284951 TI - Conditions contributing to streptococcal virulence; intra-phasic attenuation by sulfanilamide. PMID- 20284953 TI - The cultivation of Bacterium tularense in embryonated eggs. PMID- 20284954 TI - Actinomycetin. PMID- 20284958 TI - Testing of fungicidal materials against pathogenic fungi. PMID- 20284959 TI - Streptomycin in the treatment of pyocyaneus infections of the urinary tract. PMID- 20284972 TI - The production of apparent cycles in bacterial variation. PMID- 20284970 TI - Studies on penicillinase; the effect of antipenicillinase on penicillin-resistant organisms. PMID- 20284973 TI - The influence of pretreating bacteria with anionic agents on the antibacterial action of cationic germicides. PMID- 20284974 TI - Interference between the Cambridge swine strain of influenza and the PR 8 human influenza virus. PMID- 20284975 TI - Improving streptomycin yields by strain selection and inoculum development. PMID- 20284976 TI - Use of kittens for demonstration of enterotoxin production by strains of Clostridium perringens implicated in human food poisoning. PMID- 20284977 TI - This wormy world. PMID- 20284978 TI - An in vitro method of testing the amoebicidal action of chemical agents. PMID- 20284979 TI - Culture experiments on intestinal flagellates; additional observations on flagellates from man, rodents and insect larvae. PMID- 20284980 TI - A coccidian parasite of Ephestia kuhniella Zeller and of Plodia interpunctella (Hbn) (Lepidoptera, Phycitidae). PMID- 20284981 TI - Experimental therapy of paragonimiasis in dogs. PMID- 20284982 TI - Longevity of metacercariae of Fasciola hepatica on pastures in the upper coastal region of Texas and its relationship to liver fluke control. PMID- 20284983 TI - The larval development and ecology of Aedes (Stegomyia) scutellaris (Walker, 1859) in New Guinea. PMID- 20284985 TI - Notes on the tick, Ixodes howelli Cooley and Kohls, with descriptions. PMID- 20284984 TI - A new species of mite, Ichoronyssus dentipes (Acarina: Liponyssinae), from the cotton rat. PMID- 20284986 TI - Culture experiments on intestinal flagellates; species from amphibians and reptiles. PMID- 20284987 TI - Physiological observations upon a larval Eustrongylides; the lethal mechanism of bacteria. PMID- 20284988 TI - The relationship in mice of intestinal emptying time and natural resistance to Hymenolepis. PMID- 20284989 TI - A quantitative study of phenocopy production with monochromatic ultraviolet irradiation. PMID- 20284990 TI - Cytological and experimental studies on the oocytes of fresh water pulmonates. PMID- 20284992 TI - The food-vacuole in Paramecium. PMID- 20284991 TI - The relation of blood oxygen transport to resistance to anoxia in chicks and ducklings. PMID- 20284993 TI - Poisoning and recovery in barnacles and mussels. PMID- 20284994 TI - Spectrographic analysis of plants and soils. PMID- 20284996 TI - Unidentified members of the vitamin B complex. PMID- 20284995 TI - The control of urine secretion in mammals by the pars nervosa of the pituitary. PMID- 20284997 TI - [Not Available]. PMID- 20284998 TI - Measurement of virus activity in plants. PMID- 20284999 TI - Clinical tests on comparative effectiveness of analgesic drugs. PMID- 20285000 TI - Human sacrifice and warfare as factors in the demography of pre-colonial Mexico. PMID- 20285001 TI - The inheritance of cleidocranial dysostosis. PMID- 20285002 TI - Use of life-table death-rates for comparative mortality. PMID- 20285003 TI - Factorial analysis of anthropological measurements in psychotic patients. PMID- 20285004 TI - Probabilities of death in closed population groups, illustrated by probabilities of death of white fathers after birth of children. PMID- 20285005 TI - Nutrition, growth and sexuality of the Pismo clam (Tivela stultorum). PMID- 20285006 TI - A new complex of hereditary abnormalities in the house mouse. PMID- 20285007 TI - Restitution of the brachial region of the cord following unilateral excision in the embryo. PMID- 20285008 TI - Regression and shortening of the primitive streak in the explanted chick blastoderm. PMID- 20285009 TI - Investigations on the reproductive system of Drosophila. PMID- 20285010 TI - A mass spectrometer investigation of the isotopes of xenon and krypton resulting from the fission of U225 by thermal neutrons. PMID- 20285011 TI - Measurement of the diffusion length of thermal neutrons in graphite. PMID- 20285012 TI - The diffusion length of thermal neutrons in heavy water containing lithium carbonate. PMID- 20285013 TI - Sulphanilamidopyrimidines. PMID- 20285014 TI - The synthesis of di- and trithiols. PMID- 20285015 TI - Synthesis of amino acids from substituted cyanoacetic ester; 4-alkyl-3 aminopyrazolones. PMID- 20285016 TI - The reaction of beta, beta-dichlorodiethyl sulphide with proteins. PMID- 20285017 TI - 5-Hydroxyquinoline-8-carboxylic acid; a colorimetric reagent for ruthenium. PMID- 20285018 TI - Production and properties of 2,3-butanediol; fermentation of glucose by strains of Bacillus subtilis. PMID- 20285019 TI - Production and properties of 2,3-butanediol; dissimilation of glucose by Serratia marcescens. PMID- 20285020 TI - Production and properties of 2,3-butanediol; cyclic acetals and ketals derived from levo-2,3-butanediol. PMID- 20285021 TI - The catalytic action of aluminium silicates; the dehydration of butanediol-2.3 and butanone-2 over activated Morden bentonite. PMID- 20285022 TI - Binary and ternary eutectics involving ammonium nitrate. PMID- 20285023 TI - Measurements of cure of some thermosetting resins. PMID- 20285024 TI - Note on the preparation of 1-methoxy-1,3-butadiene. PMID- 20285025 TI - Metabolism of isolated lung tissue; normal and in phosgene poisoning. PMID- 20285026 TI - The effect of beta-choloroethyl vesicants, thermal injury, and turpentine on plasma fibrin, cholesterol, and sugar of dogs and rats. PMID- 20285027 TI - A diffusion cell adapted to use in the Tiselius apparatus. PMID- 20285028 TI - On the determination of tryptophane. PMID- 20285029 TI - Further observations on the succinic dehydrogenase system and the effects of tocopherol esters. PMID- 20285030 TI - Studies on antibacterial properties of irradiated pyridoxamine. PMID- 20285031 TI - Colorimetric determination of uric acid with alkaline ferricyanide. PMID- 20285032 TI - Differentiation between ribose-3-phosphate and ribose-5-phosphate by means of the orcinol-pentose reaction. PMID- 20285033 TI - The determination of aromatic amidines in plasma and urine. PMID- 20285034 TI - The urinary sulfur partition in normal and cystinuric dogs fed labeled methionine. PMID- 20285035 TI - Methionine labeled with radioactive sulfur as an indicator of protein formation in the hepatectomized dog. PMID- 20285036 TI - A study of the mechanism of the methylene blue test for bile pigment in urine; preparation of a compound of methylene blue and bilirubin. PMID- 20285037 TI - The combination of fatty acids and related compounds with serum albumin; the nature and extent of the combination. PMID- 20285038 TI - An improved method for the preparation of pituitary adrenotropic hormone. PMID- 20285039 TI - Differential spectrophotometry of purine compounds by means of specific enzymes; determination of hydroxypurine compounds. PMID- 20285040 TI - Differential spectrophotometry of purine compounds by means of specific enzymes; determination of adenine compounds. PMID- 20285041 TI - Differential spectrophotometry of purine compounds by means of specific enzymes; studies of the enzymes of purine metabolism. PMID- 20285042 TI - The enzymatic synthesis of purine ribosides. PMID- 20285043 TI - Electrophoresis of rat plasma; the effect of adrenocorticotropic hormone. PMID- 20285044 TI - Studies on pituitary lactogenic hormone; effect of esterification with methyl alcohol. PMID- 20285045 TI - The flame photometer for the measurement of sodium and potassium in biological materials. PMID- 20285046 TI - The excretion of nicotinic acid derivatives after ingestion of tryptophane by man. PMID- 20285047 TI - Studies of protoporphyrin; a simple and improved method for the preparation of pure protoporphyrin from hemoglobin. PMID- 20285048 TI - The effect of fat on the absorption and utilization of galactose by the rat. PMID- 20285049 TI - Prevention of phenylalanine synthesis by tyrosine. PMID- 20285050 TI - The colorimetric microdetermination of urea nitrogen by the xanthydrol method. PMID- 20285051 TI - Fractionation of serum with respect to its action in enhancing tissue respiration. PMID- 20285052 TI - Studies on penicillinase; the production, partial purification, and practical application of penicillinase. PMID- 20285053 TI - Studies on penicillinase; manometric method of assaying penicillinase and penicillin, kinetics of the penicillin-penicillinase reaction, and the effects of inhibitors on penicillinase. PMID- 20285054 TI - The effect of pyridoxine analogues on tryptophane metabolism in the rat. PMID- 20285055 TI - Electrically activated ergosterol (Whittier process). PMID- 20285056 TI - The identification of three mononucleotides from tobacco mosaic virus nucleic acid. PMID- 20285057 TI - The availability of vitamin B6 in yeast and liver for growth of Saccharomyces carlsbergensis. PMID- 20285058 TI - Biotin and the synthesis of aspartic acid by microorganisms. PMID- 20285059 TI - Substitution of thiamine by certain amino acids in the nutrition of Bacillus paraalvei. PMID- 20285060 TI - Nucleolytic and proteolytic activities of the new crystalline protein from beef pancreas. PMID- 20285061 TI - Carbon dioxide utilization in the formation of glycine and acetic acid. PMID- 20285062 TI - Isolation of alpha-phosphotrihydroxyglutaric acid from dog liver. PMID- 20285063 TI - Rapid extraction of human erythrocyte cholinesterase by alkali pseudoagglutination. PMID- 20285064 TI - The stimulation of bacteriophage synthesis by indole-3-acetic acid. PMID- 20285065 TI - Addition of dinitrogen tetroxide to olefins; general introduction. PMID- 20285066 TI - Addition of dinitrogen tetroxide to olefins; ethylene. PMID- 20285067 TI - Addition of dinitrogen tetroxide to olefins; propylene. PMID- 20285068 TI - Contributions to the chemistry of pyridine; condensation of beta-hydroxypyridine with formaldehyde in alkaline medium. PMID- 20285069 TI - The nature of the 2-chloroethyl chlorovinyl sulphide isomers. PMID- 20285070 TI - Condensation of substituted benzaldehydes with creatinine; influence of substituents. PMID- 20285071 TI - Molecular compound formation in the polyphenyl series; some compounds formed by 4:4'-dinitrodiphenyl. PMID- 20285072 TI - Steric inhibition of resonance; the basic strengths of some dimethyl-substituted aromatic primary and tertiary amines. PMID- 20285073 TI - The application of the method of molecular rotation differences to steroids; steroidal hormones and bile acids. PMID- 20285074 TI - The difluoroarsines. PMID- 20285075 TI - The alkyl- and aryl-substituted fluorides of sulphur, selenium, tellurium, and iodine. PMID- 20285076 TI - The chemistry of the higher silanes; tetrasilane. PMID- 20285077 TI - The structure of adreno-cortical metabolites; delta 9:11-androstene-3:17-dione. PMID- 20285078 TI - Steroids and the Walden inversion; derivatives of androstane and cholestane. PMID- 20285079 TI - Steroids and the Walden inversion; derivatives of delta 5-cholestene and delta 5 androstene. PMID- 20285080 TI - A study of the mechanism of oxidation with chromic acid. PMID- 20285081 TI - Decomposition reactions of the aromatic diazo-compounds; the mechanism of formation of azo-compounds, polyaryls, and aryl sulphides. PMID- 20285082 TI - The photochemical instability of cis- and trans-4:4'-diamidinostilbene. PMID- 20285083 TI - An argument for early treatment. PMID- 20285084 TI - Children's dentistry and the orthodontist. PMID- 20285085 TI - Dental caries in China. PMID- 20285086 TI - Fluorine and dental caries. PMID- 20285087 TI - The amino acids and their deaminating systems present in human saliva. PMID- 20285088 TI - Ammonia production in the oral cavity and the use of ammonium salts for the control of dental caries. PMID- 20285089 TI - The role of nuclear physics in medicine and dentistry; applications in medicine. PMID- 20285091 TI - Hyperparathyroidism. PMID- 20285090 TI - The role of nuclear physics in medicine and dentistry; use of radioactive tracers in the study of bones and teeth. PMID- 20285092 TI - The normal and pathologic physiology of the parathyroid glands. PMID- 20285093 TI - Dental disease in animals. PMID- 20285094 TI - The future of dentistry. PMID- 20285095 TI - A camera arm for clinical photography. PMID- 20285096 TI - Rational clinical procedure in complete immediate denture prosthesis. PMID- 20285097 TI - Periodontal conditions associated with buckling of the lower anterior teeth; etiology, diagnosis and treatment. PMID- 20285098 TI - Enamel hypoplasia in human teeth; an examination of its causes. PMID- 20285099 TI - Preservation of Borrelia vincenti and cultured strains of Treponema pallidum by the lyophil process. PMID- 20285100 TI - Plummer-Vinson syndrome; report of a case. PMID- 20285101 TI - Advanced age in relation to dental caries in white rats. PMID- 20285102 TI - Physiologic pigmentation of the oral and cutaneous tissues in the Negro. PMID- 20285103 TI - Anesthesia induced by local refrigeration of the jaws. PMID- 20285104 TI - The relation of penicillin to induced rat dental caries and oral L. acidophilus. PMID- 20285105 TI - A study of the Syrian hamster, its molars, and their lesions. PMID- 20285106 TI - The oral bacterial flora as related to dental caries in the Syrian hamster. PMID- 20285107 TI - Dental caries in the Syrian hamster; the effect of topical NaF and urea applications on caries activity. PMID- 20285108 TI - Variations in counts of lactobacilli made from single specimens of saliva. PMID- 20285109 TI - Saliva incubated with glucose as a replacement for tryptophane in a synthetic medium supporting the production of acid by Lactobacillus acidophilus. PMID- 20285110 TI - Changes of carboxyl-CO2 and of ammonia plus-urea nitrogen in saliva incubated with glucose. PMID- 20285111 TI - Arginine-arginase relationship in regeneration, repair and development of neoplasms. PMID- 20285112 TI - The supporting tissues of the tooth in acute secondary agranulocytosis (arsphenamin neutropenia). PMID- 20285113 TI - Rachitic changes of the mandibular condyle of the rat. PMID- 20285114 TI - Comparative alveolar pathology in sheep and goats. PMID- 20285115 TI - Cysts of the jaws; saving involved vital teeth by tube drainage. PMID- 20285116 TI - Multiple fractures of the facial bones; report of a case. PMID- 20285117 TI - Sulfadiazine reactions; report of three cases. PMID- 20285118 TI - Cellulitis of the face complicated by brain abscess; report of case. PMID- 20285119 TI - Ludwig's angina with overwhelming widespread sepsis; report of case. PMID- 20285121 TI - Surgical correction of mandibular prognathism; report of case. PMID- 20285120 TI - Hereditary hypertrophy of the maxilla and mandible; report of case. PMID- 20285122 TI - Compound completely displaced fracture of the mandible; report of case. PMID- 20285123 TI - The problem of hemophilia in oral surgery. PMID- 20285124 TI - Tantalum in temporomandibular arthroplasty; report of case. PMID- 20285125 TI - Fractures involving the mandibular condyle; a post-treatment survey of 120 cases. PMID- 20285126 TI - Osteomyelitis of the maxilla; report of case. PMID- 20285127 TI - Salivary calculus in Wharton's duct; report of case. PMID- 20285128 TI - Adamantinoma (ameloblastoma) of the mandible. PMID- 20285129 TI - Dentigerous cyst of the mandible; report of case. PMID- 20285130 TI - The effects of pH on the antifungal activity of fatty acids and other agents; preliminary report. PMID- 20285131 TI - The influence of experimental conditions on the results of in vitro tests for antifungal action (with special reference to the effect of maintaining solubility of the agents). PMID- 20285132 TI - Penicillin and sweat. PMID- 20285133 TI - Studies of the effects of glycerite of hydrogen peroxide upon infections of the skin and mucous membranes. PMID- 20285134 TI - Staphylococci and hemolytic streptococci from normal skin, and from cutaneous infections. PMID- 20285135 TI - New surface active antibiotics. PMID- 20285136 TI - Studies on the adherence of the epidermis to the corium. PMID- 20285137 TI - Sarcoma of the liver; disadvantages of thorotrast as a diagnostic agent. PMID- 20285138 TI - Transpleural bilateral vagotomy. PMID- 20285139 TI - Chronic cholangitis. PMID- 20285140 TI - Experiences with beta-(4-hydroxy-3,5-diiodophenyl)-alpha-phenyl-propionic acid (priodax); a dye for cholecystography. PMID- 20285141 TI - Belladonna and barbiturates in gastrointestinal spasticity. PMID- 20285142 TI - Gastritis in the toothless. PMID- 20285143 TI - Induction of ovulation in the diestrous mouse by gonadotropins. PMID- 20285144 TI - The action of human prostate slices on alpha-estradiol and estrone. PMID- 20285145 TI - Concerning the mechanism of diestrum during lactation in the albino rat. PMID- 20285146 TI - Mobilization of alkaline phosphatase in the uterus of the mouse by estrogen. PMID- 20285147 TI - Early mating and pregnancy in the monkey. PMID- 20285148 TI - The sparing effect of progesterone on the hepatic inactivation of alpha estradiol. PMID- 20285149 TI - The metabolic significance of protein-bound iodine of plasma; a study of its concentration under various conditions and of its rate of formation as measured with radioactive iodine. PMID- 20285150 TI - The incidence of delayed ovulations following abdominal operations in the domestic hen. PMID- 20285151 TI - A study of the reliability of complement fixation as a method of measuring the activities of sera of high, medium, and low antibody titer. PMID- 20285152 TI - Immunochemical studies with tagged proteins; the distribution of tobacco-mosaic virus in the mouse. PMID- 20285153 TI - Immunochemical studies with tagged proteins; the kinetics of antibody-formation. PMID- 20285154 TI - Quantitative estimation of 0 agglutinins in typhoid sera. PMID- 20285155 TI - The preparation and properties of a purified equine encephalomyelitis vaccine. PMID- 20285156 TI - Observations upon the specificity of the complement fixation test for lymphogranuloma venereum. PMID- 20285157 TI - The virus of Ilheus encephalitis; isolation, serological specificity and transmission. PMID- 20285158 TI - Purification and characters of the Newcastle disease virus (California strain). PMID- 20285159 TI - A simple lyophilizing apparatus for laboratory use. PMID- 20285160 TI - Preparation of suspensions of rickettsiae from infected yolk sacs without the use of ether. PMID- 20285161 TI - The complement fixation test in yellow fever epidemiology; the use of globulin antigen in immunity surveys. PMID- 20285162 TI - Further experimental studies on the role of the plasma cells as antibody producers. PMID- 20285163 TI - A specific antigen recovered from tissue infected with M. paratuberculosis (Johne's bacillus); further studies on the nature of the antigen and on methods for demasking it. PMID- 20285164 TI - The transition forms of blood groups. PMID- 20285165 TI - The antigenic specificity of syphilitic antibody globulin. PMID- 20285166 TI - The relationship of sulfhydryl and disulfide groups to the antigenic power of bovine serum albumin. PMID- 20285167 TI - Complement and opsonic activities of fresh human sera. PMID- 20285168 TI - Detoxification of crystalline botulinum type A toxin. PMID- 20285169 TI - Further study of the quantitative complement-fixation test as applied to the serum diagnosis of typhus fever. PMID- 20285170 TI - Specific complement-fixing diagnostic antigens for neurotropic viral diseases. PMID- 20285171 TI - The physiologic properties of thioglycolic acid and titioglycolates. PMID- 20285173 TI - Edrisal in the management of dysmenorrhea. PMID- 20285172 TI - The reconstruction of the amputation stump for weight bearing. PMID- 20285174 TI - Paraprol as a prophylactic and therapeutic agent in nickel dermatitis and chrome sores. PMID- 20285175 TI - Fractures of the lower end of the radius and ulna commonly classified as Colles' fractures. PMID- 20285176 TI - The fallacy of the term varicose ulcer. PMID- 20285177 TI - The protective effect of vaccination against epidemic influenza B in an industrial plant. PMID- 20285178 TI - Refrigeration in trauma of the extremities. PMID- 20285179 TI - Dental relations in industrial health services. PMID- 20285180 TI - Evaluation of borderline cardiovascular abnormalities. PMID- 20285181 TI - Minor illness, short medical absenteeism, lateness and separation in a mail order firm. PMID- 20285182 TI - Hydrofluoric acid burn; case report. PMID- 20285183 TI - Tropical diseases in industry. PMID- 20285184 TI - Preventive medicine in engineering education. PMID- 20285185 TI - Laceration of the liver. PMID- 20285186 TI - Low back pain; a different cause and treatment; the pronation syndrome. PMID- 20285187 TI - The action of thioglycolic acid and thioglycolates on animals after subcutaneous introduction. PMID- 20285188 TI - Scrotal swellings in industrial medical practice. PMID- 20285189 TI - Respiratory ills and their control in industry. PMID- 20285190 TI - Recent research on chemical injuries to the eye. PMID- 20285191 TI - Military morality. PMID- 20285192 TI - The well-informed citizen; an essay on the social distribution of knowledge. PMID- 20285193 TI - Influence of tyrothricin in the sterilization and cicatrization of leprous ulcers; report of treatment in 15 patients. PMID- 20285194 TI - The action of diasone in the treatment of leprosy; preliminary report. PMID- 20285195 TI - Present status of promin treatment in leprosy. PMID- 20285196 TI - Penicillin in treatment of leprosy; trial in eight cases. PMID- 20285197 TI - Alopecia leprosa in the United States. PMID- 20285198 TI - Erythema nodosum in leprosy; a study of the pathogenesis with reference to carbohydrate metabolism. PMID- 20285199 TI - National Leprosy Service in Bolivia. PMID- 20285200 TI - Control of leprosy in Colombia. PMID- 20285202 TI - PROPHYLAXIS of leprosy in Brazil. PMID- 20285201 TI - A new method for staining leprosy bacilli. PMID- 20285203 TI - LEPROSY in the Philippines. PMID- 20285204 TI - A new method of osteoplastic amputation and reamputation of the femur. PMID- 20285205 TI - Treatment of contractures with novocaine block. PMID- 20285206 TI - Action of prostigmine on paralysis following cerebral trauma. PMID- 20285207 TI - The influence of extracortical factors on the function of the central nervous system. PMID- 20285208 TI - Study of the structure of micro-organisms with the aid of the electron microscope. PMID- 20285209 TI - Spontaneous rupture of the spleen. PMID- 20285210 TI - The significance of lymph and other elements of the lymphatic system in antivirus immunity. PMID- 20285212 TI - The fight against intestinal infections. PMID- 20285211 TI - New type of vaccine from typhus lice. PMID- 20285213 TI - New blood albumin substitute. PMID- 20285214 TI - Treatment of diabetes mellitus without insulin. PMID- 20285215 TI - Restoration of heart rhythm during fibrillation by a condenser discharge. PMID- 20285216 TI - Stimulating properties of granulation tissue. PMID- 20285217 TI - The new Soviet curriculum in medicine. PMID- 20285218 TI - Bearing of general nutritional state on atherosclerosis. PMID- 20285219 TI - Necrosis of renal papillae and acute pyelonephritis in diabetes mellitus. PMID- 20285220 TI - Eosinophilic granuloma of bone; report of a case with multiple lesions of bone and pulmonary infiltration. PMID- 20285221 TI - Induced malaria of foreign origin. PMID- 20285222 TI - Actinomycotic endocarditis; report of two cases with a review of the literature. PMID- 20285223 TI - Cardiac manifestations of toxic action of emetine hydrochloride in amebic dysentery. PMID- 20285224 TI - Penicillin in the treatment of keratosis blennorrhagica with polyarthritis. PMID- 20285225 TI - Objective studies of some physiologic responses in mild chronic trench foot. PMID- 20285226 TI - The use of the psychosomatic concept in medicine. PMID- 20285227 TI - The use of the psychosomatic concept in social case work. PMID- 20285228 TI - The elimination of poliomyelitis virus from the human mouth or nose. PMID- 20285229 TI - The clinical use of cytochrome C in patients with intermittent claudication. PMID- 20285230 TI - The ausculatory findings in patent ductus arteriosus. PMID- 20285231 TI - The diagnosis of ruptured membranes by the vaginal smear. PMID- 20285232 TI - Roentgenological changes of the small intestine in sprue. PMID- 20285233 TI - Surgical management of gastric and duodenal ulcer. PMID- 20285234 TI - Observations on abdominal surgery in warfare. PMID- 20285235 TI - The etiology of pruritis ani. PMID- 20285236 TI - War and nerves. PMID- 20285237 TI - The etiology of peptic ulcer in the light of vagus surgery. PMID- 20285238 TI - Experiences with the use of universal donor blood and pooled plasma. PMID- 20285239 TI - Various forms of hypogonadism. PMID- 20285240 TI - Roentgenologic appearance of the gastro-intestinal tract in scleroderma. PMID- 20285241 TI - The technique of back examination and interpretation of the findings. PMID- 20285242 TI - A plan for analysis of the biologic factors involved in experimental carcinogenesis of the thyroid by means of radioactive isotopes. PMID- 20285243 TI - Masculinization and pregnancy; a case report. PMID- 20285244 TI - Recent studies of hemorrhagic shock. PMID- 20285245 TI - Adreno-pituitary relationships. PMID- 20285246 TI - Psychotherapeutic opportunities for the general practitioner. PMID- 20285247 TI - Sprue. PMID- 20285248 TI - Some aspects of military medicine applicable to civilian practice. PMID- 20285249 TI - Rheumatic heart disease in pregnancy. PMID- 20285250 TI - Tuberculous disease of the bones and joints. PMID- 20285251 TI - Surgery of the colon. PMID- 20285253 TI - The treatment of pneumococcic penumonia with penicillin and sulfadiazine. PMID- 20285259 TI - Recent advances in neurology. PMID- 20285255 TI - Nitrous oxide and oxygen anesthesia with curare relaxation. PMID- 20285261 TI - Heart catheterization in the investigation of congenital heart disease. PMID- 20285262 TI - Some observations on nasal cilia. PMID- 20285263 TI - A new method of ureterointestinal anastomosis prior to total cystectomy for carcinoma of the bladder. PMID- 20285264 TI - The importance of blood changes in coronary occlusion. PMID- 20285265 TI - Ectopic pregnancy as a diagnostic problem (a study of 100 cases). PMID- 20285266 TI - Sudden death. PMID- 20285267 TI - Anaesthesia for plastic surgery. PMID- 20285268 TI - The problem of muscle relaxation in surgery. PMID- 20285269 TI - Phlebothrombosis and its treatment. PMID- 20285270 TI - Anaesthesia in thoracic surgery. PMID- 20285271 TI - Bone lesions encountered during infancy. PMID- 20285272 TI - Penicillin in the treatment of sinusitis. PMID- 20285273 TI - The treatment of mastoiditis in children. PMID- 20285274 TI - The psychological component. PMID- 20285275 TI - Vertigo. PMID- 20285276 TI - Occupational therapy in rheumatoid arthritis. PMID- 20285277 TI - Bone plating for fractures of the mandible. PMID- 20285278 TI - Pregnancy associated with adenomyoma of the uterus. PMID- 20285279 TI - Staphylococcic pyaemia due to breast abscess in an infant. PMID- 20285280 TI - Polyostotic fibrous dysplasia. PMID- 20285281 TI - Cutaneous myiasis occurring in Western Canada. PMID- 20285282 TI - The use of a metallic glenoid rim in recurrent dislocation of the shoulder. PMID- 20285283 TI - No disease. [misconception of psychiatric principles and functional disability]. PMID- 20285284 TI - Newer aspects of virus hepatitis. PMID- 20285285 TI - Ocular tuberculosis; three case reports. PMID- 20285286 TI - The premedical program. PMID- 20285288 TI - The kidney and kidney function tests. PMID- 20285287 TI - [Chorioepithelioma of the uterus with metastases to lungs and possibly to the brain]. PMID- 20285289 TI - Diagnosis of peripheral arterial diseases. PMID- 20285290 TI - Tumor clinics of Connecticut. PMID- 20285291 TI - Progress in the treatment of alcoholism. PMID- 20285292 TI - Medical program at Newington Veterans Hospital. PMID- 20285293 TI - The rooming-in plan for mothers and newborn infants. PMID- 20285294 TI - [Cystic fibrosis of pancreas]. PMID- 20285295 TI - Psychosomatic elements; when the foreman is a pain in the neck. PMID- 20285296 TI - Development of high educational standards by the medical profession. PMID- 20285297 TI - Medical progress and medical education during the war. PMID- 20285298 TI - Medical education in Europe. PMID- 20285300 TI - Sensitivity to liver injections. PMID- 20285299 TI - Two cases of spontaneous pneumothorax in children and their treatment. PMID- 20285301 TI - Local public health service. PMID- 20285302 TI - Tetanus immunization. PMID- 20285303 TI - The positive serological reaction is not a diagnosis of syphilis. PMID- 20285304 TI - Refrigeration in surgery of the extremities. PMID- 20285305 TI - Staphylococcus pneumonia in children; roentgen aspects. PMID- 20285306 TI - Marked hyperproteinemia in subacute bacterial endocarditis (and simultaneous hyperthyroidism and subacute bacterial endocarditis). PMID- 20285307 TI - Streptococcus viridans meningitis with pneumonia. PMID- 20285308 TI - Reflections based on psychiatric work in an Army General Hospital in the ETO. PMID- 20285309 TI - Diagnosis and treatment of blepharoptosis. PMID- 20285310 TI - Periodic physical examinations in apparently well women. PMID- 20285311 TI - Systemic blastomycosis. PMID- 20285312 TI - Saccular aneurysm of the carotid artery. PMID- 20285313 TI - Abdominal lymphosarcoma. PMID- 20285314 TI - Q fever in the United States; epidemiologic studies of an outbreak among stock handlers and slaughterhouse workers. PMID- 20285315 TI - Q fever in the United States; clinical data on an outbreak among stock handlers and slaughterhouse workers. PMID- 20285316 TI - Q fever in the United States; serologic observations in an outbreak among stock handlers and slaughterhouse workers. PMID- 20285317 TI - Q fever in the United States; isolation and identification of rickettsias in an outbreak among stock handlers and slaughterhouse workers. PMID- 20285318 TI - The knowledge of human virus infections of animal origin. PMID- 20285319 TI - Choice of anesthesia in orthopedic surgery. PMID- 20285320 TI - Infectious granulomatous lesions of the cervix. PMID- 20285321 TI - Reactions to penicillin; procaine hydrochloride intravenously in the treatment of reactions similar to serum sickness. PMID- 20285322 TI - DEATH following the use of analbis suppositories. PMID- 20285323 TI - [Resident training program in Veterans Administration hospitals]. PMID- 20285324 TI - Hospital facilities and health centers for rural areas. PMID- 20285325 TI - TAFT-SMITH-BALL-DONNELL National Health Bill. PMID- 20285326 TI - Cancer of the thyroid gland. PMID- 20285327 TI - Injuries involving the accessory nasal sinuses. PMID- 20285328 TI - Surgical experiences with vascular disease. PMID- 20285329 TI - Dislocated intervertebral disk of the lumbar region. PMID- 20285330 TI - The history of civilian medical care in Key West to 1945. PMID- 20285331 TI - The role of the Rh factors in clinical medicine. PMID- 20285332 TI - Ligation of the inferior vena cava for the prevention of pulmonary embolism; report of a case. PMID- 20285333 TI - Combined pregnancy; report of a case. PMID- 20285336 TI - Survey of the treatment of syphilis. PMID- 20285335 TI - Care of intertrochanteric fractures of femur. PMID- 20285334 TI - Ten thousand spinal anesthesias; five thousand with ephedrine intrathecally; random comment. PMID- 20285337 TI - Pruritis ani. PMID- 20285338 TI - Treatment of gonorrhea in the male with penicillin. PMID- 20285339 TI - Mental hygiene for the general practitioner. PMID- 20285340 TI - A story about milk. PMID- 20285341 TI - Observations of a general practitioner. PMID- 20285343 TI - An evaluation of allergy in general practice. PMID- 20285342 TI - Acute hepatitis. PMID- 20285344 TI - Ligation of the ductus arteriosus with a superimposed subacute bacterial endocarditis; report of a case treated successfully by ligation. PMID- 20285345 TI - Tuberculosis of the breast. PMID- 20285346 TI - The Rh factor and physiologic jaundice of the newborn. PMID- 20285347 TI - [Blastomycosis cutis]. PMID- 20285348 TI - Physical rehabilitation of the severely handicapped. PMID- 20285349 TI - Carcinoma of the rectum; a review of 215 cases. PMID- 20285350 TI - Biopsy. PMID- 20285351 TI - PHYSICIAN's place in medical problems. PMID- 20285352 TI - Anaphylactic shock in egg-sensitive individuals following vaccination with typhus vaccine; a study of the antigenic relationship of egg and chicken meat antigens and typhus vaccine. PMID- 20285353 TI - The relationship of gastric acidity to thiamine excretion in the aged. PMID- 20285354 TI - The evaluation of the vitamin C status of human subjects: studies with intradermal dye discoloration, capillary fragility, fasting plasma vitamin C level, and vitamin C saturation. PMID- 20285355 TI - Serum proteins in hypoproteinemia due to nutritional deficiency. PMID- 20285356 TI - Folic acid in the treatment of aplastic anemia. PMID- 20285357 TI - Aplastic anemia following administration of thorotrast. PMID- 20285358 TI - Studies on leucocyte granules after staining with sudan black B and May-Grunwald Giemsa. PMID- 20285359 TI - A study of the sternal marrow and peripheral blood of 55 patients with plasma cell myeloma. PMID- 20285360 TI - The influence of heat and formalin upon the Rh agglutinogen. PMID- 20285361 TI - Benzidine-negative stools during iron therapy. PMID- 20285362 TI - Hyperparathyroidism and partial heart block. PMID- 20285363 TI - Sensitivity of Eberthelia typhosa to penicillin fractions G and X. PMID- 20285364 TI - Phosphatases and inorganic phosphorus in normal human serum. PMID- 20285365 TI - Rapid continuous extraction and determination of quinine. PMID- 20285366 TI - The counting of blood cells by dark-field illumination. PMID- 20285367 TI - Clorox and tergitol-Javelle water mixture for acid-fast bacilli concentration; a comparative study. PMID- 20285368 TI - Microprecipitating unit for blood and tissue proteins. PMID- 20285369 TI - A simple apparatus for quantitative microcolorimetric analysis in final volumes of 0.15 c.c. PMID- 20285370 TI - Diet and the liver. PMID- 20285371 TI - Anesthesia in general practice. PMID- 20285372 TI - Thiouracil in the management of hyperthyroidism. PMID- 20285373 TI - The immunology of poliomyelitis. PMID- 20285374 TI - Preoperative management of hyperthyroidism; use of thiouracil and thiobarbital. PMID- 20285375 TI - Brachial neuralgia. PMID- 20285376 TI - Rocky Mountain spotted fever; case report and discussion of therapy. PMID- 20285377 TI - Analgesia of the brachial plexus. PMID- 20285378 TI - Volvulus of the small intestine. PMID- 20285379 TI - Our battle for freedom. PMID- 20285380 TI - Further observations on the two-hour pregnancy test. PMID- 20285381 TI - Puerperal inversion of the uterus. PMID- 20285382 TI - Tropical dermatoses among naval personnel in the South-Pacific area. PMID- 20285383 TI - Sporotrichosis. PMID- 20285384 TI - Diphtheria antitoxin and other foreign proteins in the treatment of herpes zoster ophthalmicus. PMID- 20285385 TI - Perinephritic abscess. PMID- 20285386 TI - Multiple sclerosis. PMID- 20285387 TI - Dissolution of staghorn calculus in kidney pelvis by intermittent irrigation with solution G. PMID- 20285388 TI - Ear canal infections. PMID- 20285389 TI - The surgery of deafness due to otosclerosis. PMID- 20285391 TI - Myopia. PMID- 20285390 TI - Institutional treatment of syphilis. PMID- 20285392 TI - An epidemiological study of pinworms in patients at Oklahoma Hospital for Crippled Children. PMID- 20285393 TI - Early ambulation in obstetrics and gynecology. PMID- 20285394 TI - Hemoglobin levels of Parker High School students. PMID- 20285395 TI - An analysis of 107 cesarean sections. PMID- 20285396 TI - Health legislation enacted by the Seventy-fifth General Assembly. PMID- 20285397 TI - The management of traumatic hemothorax. PMID- 20285398 TI - Past progress and future program of tuberculosis control. PMID- 20285399 TI - Cancer of the breast. PMID- 20285401 TI - Surgical treatment of carcinoma of the stomach. PMID- 20285400 TI - Face presentation; report of a case. PMID- 20285402 TI - Thiouracil will not replace thyroidectomy. PMID- 20285403 TI - Stuttering; report of a case. PMID- 20285404 TI - The University of Louisville School of Medicine. PMID- 20285405 TI - Summer diarrhea of infants and children in office practice. PMID- 20285406 TI - Minor surgery, some considerations that may interest the family physician. PMID- 20285407 TI - Traumatic diaphragmatic hernia. PMID- 20285408 TI - Questions of current interest in the Swedish medical world. PMID- 20285409 TI - Removal of superfluous hair by monopolar coagulation. PMID- 20285410 TI - The District of Columbia Medical Society ragweed pollen count. PMID- 20285411 TI - A clinical evaluation of liver disease with special reference to portal cirrhosis. PMID- 20285413 TI - Peptic ulcer. PMID- 20285412 TI - The contraceptive diaphragm: improved technic. PMID- 20285414 TI - The clinical importance of stomach muscle. PMID- 20285415 TI - Results of Mantoux survey carried out at Perth Children's Hospital. PMID- 20285416 TI - Traumatic radio-humeral synovitis. PMID- 20285417 TI - Rupture of an abdominal aneurysm into the alimentary canal. PMID- 20285418 TI - Purulent meningitis in early infancy. PMID- 20285419 TI - The treatment of thyreotoxicosis by concurrent administration of thiouracil and iodine. PMID- 20285420 TI - Surgical treatment of deafness; the fenestration operation for otosclerosis. PMID- 20285421 TI - Inguinal sprain. PMID- 20285422 TI - A case of anaemia of the pernicious type. PMID- 20285423 TI - Developmental defects. PMID- 20285424 TI - Glaucoma following herpes. PMID- 20285425 TI - Cervical and thoracic intervertebral disk disease. PMID- 20285426 TI - Chromoblastomycosis. PMID- 20285427 TI - The university and clinical teaching. PMID- 20285428 TI - Infectious mononucleosis; some aspects of its etiology. PMID- 20285429 TI - Malignant melanoma with generalized skin blackening; the white girl who turned black. PMID- 20285430 TI - Modern surgical methods. PMID- 20285431 TI - Postoperative parenteral fluids; with particular reference to use of saline and amino acids. PMID- 20285432 TI - Drug toxicity in renal and hepatic disease. PMID- 20285433 TI - High external gastrostomy opening in upper esophageal obstructions. PMID- 20285434 TI - Ringworm of scalp in Pacific Northwest. PMID- 20285435 TI - Chromaffin tissue tumors and associated paroxysmal hypertension. PMID- 20285436 TI - Are mass presumptive serologic surveys justified by the present statuses of serodiagnostic tests and of syphilis? PMID- 20285437 TI - Acute appendicitis occurring during penicillin therapy. PMID- 20285438 TI - Relation of the diseases of the paranasal sinuses to affections of the optic nerve. PMID- 20285439 TI - The problem of tuberculosis control. PMID- 20285440 TI - What the doctor should know about housing. PMID- 20285441 TI - The critical analysis of 250 deliveries under continuous caudal analgesia. PMID- 20285442 TI - Perforating duodenal ulcer associated with burns. PMID- 20285443 TI - Relation of survival time of respiratory gasping mechanism of the isolated mouse head to age. PMID- 20285444 TI - Effects of urethan (ethyl carbamate) on mitosis. PMID- 20285445 TI - Persistence of resistance of tubercle bacilli to streptomycin during passage through guinea pigs. PMID- 20285446 TI - Uniformity of size of bacteriophage particles. PMID- 20285447 TI - Effect of 2,3-dimercaptopropanol (BAL) on acute poisoning by tervalent and quinquevalent antimonial drugs. PMID- 20285448 TI - Electron micrographs of bacterial cultures infected with bacteriophage. PMID- 20285449 TI - Sugar alcohols: sorbitol and sorbitan as precursors of liver-glycogen in the rat. PMID- 20285450 TI - Alteration of the distribution and excretion of streptomycin. PMID- 20285451 TI - The use of the mouse in studies on streptomycin. PMID- 20285452 TI - Proteins with growth-promoting action on tissue cells in vitro. PMID- 20285453 TI - Changes in concentration of enzymes in pancreatic juice after giving insulin. PMID- 20285454 TI - Some effects of desoxycorticosterone acetate on mice irradiated with X-rays. PMID- 20285455 TI - Quantitative measurement of growth of Mycobacterium tuberculosis; effect of streptomycin. PMID- 20285456 TI - Preparation of an anti-ulcer factor from human urine. PMID- 20285457 TI - Antagonism of the hemorrhagic syndrome induced by derivatives of 3-hydroxy-1,4 naphthoquinone. PMID- 20285458 TI - Action of 3,3' methylenebis (4-hydroxycoumarin) (dicumarol) on thromboplastic activity of rabbit brain. PMID- 20285459 TI - Grisein, a new antibiotic produced by a strain of Streptomyces griseus. PMID- 20285460 TI - Determination of oxygen consumption in the albino rat. PMID- 20285462 TI - The corneal and lenticular changes resulting from amino acid deficiencies in the rat. PMID- 20285461 TI - The susceptibility to furacin of bacterial strains resistant to sulfonamides or antibiotics. PMID- 20285463 TI - Chemical changes in the developing turtle embryo. PMID- 20285464 TI - Effect of anemic anoxia on absorption of isotonic magnesium sulfate from the small intestine. PMID- 20285465 TI - Estimation of steroid estrogens by fluorimetry. PMID- 20285466 TI - Induction of renal glomerular lesions by urethane in inbred mice susceptible to spontaneous glomerulonephritis. PMID- 20285467 TI - Coproporphyrinuria (Type III) in acute poliomyelitis. PMID- 20285468 TI - Experimental evidence of the secretion of urine by the fetal kidney. PMID- 20285469 TI - Role of hemoconcentration in production of gastric and duodenal ulcer following experimental burns. PMID- 20285470 TI - Comparative utilization of raw and autoclaved soy bean protein by the human. PMID- 20285471 TI - Susceptibility of the bear to fox encephalitis. PMID- 20285472 TI - Two related Salmonella types, S. luciana and S. marseille. PMID- 20285473 TI - Plasma protein concentrations and organ weights of rats as related to a high protein diet. PMID- 20285474 TI - Pyribenzamine aerosol inhalation and its influence on histamine poisoning and anaphylaxis. PMID- 20285475 TI - In vitro observations of the mode of action of streptomycin. PMID- 20285476 TI - Similarities in electron micrographs of purified Lansing and SK poliomyelitis virus. PMID- 20285477 TI - Further studies of factor R. PMID- 20285478 TI - Nerve conduction after inactivation of choline esterase. PMID- 20285479 TI - Platelet fragility in man. PMID- 20285480 TI - Effect of 2-methyl-1,4-naphthoquinone on glycolysis of Schistosoma mansoni. PMID- 20285481 TI - A practical method for routine blood cultures in brucellosis. PMID- 20285482 TI - Hematologic effects of pteroylglutamic acid (folic acid) in man. PMID- 20285483 TI - Antibiotic activity of certain molds against Brucella. PMID- 20285484 TI - Effect of paraaminohippurate on mannitol determinations by the periodate-iodide thiosulfate method. PMID- 20285485 TI - Factors not synthesized by yeast in the presence of cyanide. PMID- 20285486 TI - Effects of various anesthetic agents on the blood pressure of the white rat. PMID- 20285488 TI - Clinical aspects of polyarteritis nodosa. PMID- 20285487 TI - The classification of cases of glycosuria. PMID- 20285489 TI - Glycogen disease. PMID- 20285490 TI - The aetiology of chloroma and the nature of the green pigment; a report of three cases. PMID- 20285491 TI - The location of autonomic centers in the cerebral cortex. PMID- 20285492 TI - Charter for world health. PMID- 20285493 TI - Physiology in medical education. PMID- 20285494 TI - Rhode Island's water pollution problem. PMID- 20285495 TI - Pediatric problems of the general practitioner. PMID- 20285496 TI - Podophyllin in the treatment of cutaneous vegetations. PMID- 20285497 TI - Otosclerosis, progressive deafness and correlated problems; what has research discovered and what does the future promise? PMID- 20285498 TI - Heart disease and employment. PMID- 20285499 TI - Residency and fellowship program at R. I. Hospital. PMID- 20285500 TI - Studies in hepatic function. PMID- 20285501 TI - Mediterranean or Cooley's anemia; a case report. PMID- 20285502 TI - A comparison of the volumes of blood, plasma, and circulating cells in secondary polycythemia and in severe anemia. PMID- 20285503 TI - A case of corneal ulcer treated with penicillin solution. PMID- 20285504 TI - Tuberculosis case finding and control in hospital personnel. PMID- 20285505 TI - Hospitals in the post-war world. PMID- 20285506 TI - Studies in chemotherapy of tuberculosis culminating in the use of streptomycin. PMID- 20285507 TI - The pupil in differential diagnosis. PMID- 20285508 TI - Progress in endocrinology. PMID- 20285509 TI - Criminal or syphilitic? PMID- 20285510 TI - The place of physical medicine in general practice. PMID- 20285511 TI - A treatment for sebaceous cysts. PMID- 20285512 TI - Not every patient with urinary symptoms or signs should have complete urologic study. PMID- 20285513 TI - Antiseptics, old and new penicillin. PMID- 20285514 TI - [Not Available]. PMID- 20285515 TI - [Not Available]. PMID- 20285517 TI - [Not Available]. PMID- 20285516 TI - [Not Available]. PMID- 20285518 TI - [Not Available]. PMID- 20285519 TI - [Not Available]. PMID- 20285520 TI - [Not Available]. PMID- 20285521 TI - [Not Available]. PMID- 20285523 TI - Some observations on the classification and diagnostic criteria of heart diseases. PMID- 20285522 TI - The treatment of tularemia with streptomycin; report of three cases. PMID- 20285524 TI - Rutin in the treatment of increased capillary fragility; a preliminary report. PMID- 20285525 TI - Neurosurgical complications of injuries about the head and face. PMID- 20285526 TI - Diabetic acidosis; a review of 105 cases. PMID- 20285527 TI - Experiences of an ophthalmologist aboard a hospital ship. PMID- 20285528 TI - Mediastinal sympathoblastoma (neuroblastoma); report of two cases with necropsies and review of the literature. PMID- 20285529 TI - Persistently sero-positive reaction for syphilis in chronic brucellosis. PMID- 20285530 TI - Simplified Rubin test technique. PMID- 20285531 TI - Is partial gastrectomy desirable in the treatment of duodenal ulcer? PMID- 20285532 TI - [Not Available]. PMID- 20285533 TI - [Not Available]. PMID- 20285534 TI - [Not Available]. PMID- 20285535 TI - [Not Available]. PMID- 20285536 TI - [Not Available]. PMID- 20285537 TI - [Not Available]. PMID- 20285538 TI - [Not Available]. PMID- 20285539 TI - [Not Available]. PMID- 20285540 TI - [Not Available]. PMID- 20285541 TI - [Not Available]. PMID- 20285542 TI - [Not Available]. PMID- 20285543 TI - [Not Available]. PMID- 20285544 TI - [Not Available]. PMID- 20285545 TI - [Not Available]. PMID- 20285546 TI - [Not Available]. PMID- 20285548 TI - [Not Available]. PMID- 20285547 TI - [Not Available]. PMID- 20285549 TI - [Not Available]. PMID- 20285550 TI - [Not Available]. PMID- 20285551 TI - [Not Available]. PMID- 20285552 TI - [Not Available]. PMID- 20285553 TI - [Not Available]. PMID- 20285554 TI - [Not Available]. PMID- 20285555 TI - [Not Available]. PMID- 20285556 TI - [Not Available]. PMID- 20285557 TI - [Not Available]. PMID- 20285558 TI - [Not Available]. PMID- 20285559 TI - [Not Available]. PMID- 20285560 TI - [Not Available]. PMID- 20285561 TI - [Not Available]. PMID- 20285562 TI - [Not Available]. PMID- 20285563 TI - [Not Available]. PMID- 20285564 TI - [Not Available]. PMID- 20285565 TI - [Not Available]. PMID- 20285566 TI - [Not Available]. PMID- 20285568 TI - [Not Available]. PMID- 20285567 TI - [Not Available]. PMID- 20285569 TI - [Not Available]. PMID- 20285570 TI - [Not Available]. PMID- 20285571 TI - [Not Available]. PMID- 20285572 TI - [Not Available]. PMID- 20285573 TI - [Not Available]. PMID- 20285574 TI - [Not Available]. PMID- 20285575 TI - [Not Available]. PMID- 20285576 TI - [Not Available]. PMID- 20285578 TI - [Not Available]. PMID- 20285577 TI - [Not Available]. PMID- 20285579 TI - [Not Available]. PMID- 20285580 TI - [Not Available]. PMID- 20285581 TI - [Not Available]. PMID- 20285582 TI - [Not Available]. PMID- 20285583 TI - [Not Available]. PMID- 20285584 TI - [Not Available]. PMID- 20285585 TI - [Not Available]. PMID- 20285586 TI - [Not Available]. PMID- 20285587 TI - [Not Available]. PMID- 20285588 TI - [Not Available]. PMID- 20285589 TI - [Not Available]. PMID- 20285590 TI - [Not Available]. PMID- 20285591 TI - [Not Available]. PMID- 20285592 TI - [Not Available]. PMID- 20285593 TI - [Not Available]. PMID- 20285594 TI - [Not Available]. PMID- 20285595 TI - [Not Available]. PMID- 20285596 TI - [Not Available]. PMID- 20285597 TI - [Not Available]. PMID- 20285598 TI - Erasmus Wilson on ringworm. PMID- 20285599 TI - Heterologous transplantation of uro-epithelial tumors; transplantation of bladder tumors. PMID- 20285600 TI - The alleviation of pylorospasm and colic in infants by reducing the volume of the food intake per feeding. PMID- 20285601 TI - The pelvic survey. PMID- 20285602 TI - An introduction to the study on the nervous system of Ateles. PMID- 20285604 TI - The vision and daring of youth, the story of the introduction of surgical anesthesia. PMID- 20285603 TI - The contribution of anesthesia to psychiatry. PMID- 20285605 TI - FURTHER progress in food research. PMID- 20285606 TI - THERAPEUTIC measures in cirrhosis of liver. PMID- 20285607 TI - AUXILIARY swinging tray for dressing carriage. PMID- 20285608 TI - The use of nitrogen mustard in the treatment of lymphomata. PMID- 20285609 TI - DUTIES of the preventive medicine officer. PMID- 20285610 TI - Two cases of cachexia. PMID- 20285611 TI - A case of coma. PMID- 20285612 TI - Streptomycin therapy in brucellosis. PMID- 20285613 TI - Food poisoning. PMID- 20285614 TI - Report of duties performed by clinical psychologist. PMID- 20285615 TI - Follicular cyst with an impacted cuspid. PMID- 20285616 TI - Foreign body localization. PMID- 20285617 TI - Rupture of the liver. PMID- 20285618 TI - An endotherm for chronic prostatitis. PMID- 20285620 TI - Compressed air atomizer. PMID- 20285619 TI - Knee support for the Albee-Comper orthopedic table. PMID- 20285621 TI - Ocular disturbances associated with malnutrition. PMID- 20285622 TI - Medical arrangements for the contact and relief of allied prisoners of war and internees in South-East Asia. PMID- 20285623 TI - The incidence of staphylococci in the nose and on the skin of Africans and Europeans in West Africa. PMID- 20285624 TI - The disinfection of mess tins in the field. PMID- 20285626 TI - Pneumonia prophylaxis in natives of East Africa. PMID- 20285625 TI - Quantitative estimation in psychiatric diagnosis. PMID- 20285627 TI - Wartime advances in medicine which might be translated into civil practice. PMID- 20285628 TI - Psychopathic personality. PMID- 20285629 TI - Fits, faints and blackouts; a review of the causes of syncope and allied states in naval personnel. PMID- 20285630 TI - Organization of a casualty reception unit. PMID- 20285631 TI - Freetown memories. PMID- 20285632 TI - A curious reflex movement of the upper eyelid in oculomotor palsy; outward deviation of the sound eye producing elevation of the paralysed upper lid in ophthalmoplegia due to intracranial aneurysm. PMID- 20285633 TI - Return to Singapore. PMID- 20285634 TI - A walking caliper for Pott's fracture. PMID- 20285635 TI - Embolism of the popliteal artery. PMID- 20285636 TI - Suppuration in a urachal cyst. PMID- 20285637 TI - Outbreak of interior poliomyelitis in H. M. S. Jamaica. PMID- 20285638 TI - Dried milk powder; the effect of season of production on keeping quality. PMID- 20285639 TI - Preservation of eggs; methods for determining yolk index. PMID- 20285640 TI - Precision of assessment of palatability of foodstuffs by laboratory panels; saltiness of bacon. PMID- 20285641 TI - Flavour reversion in hydrogenated linseed oil; the relation of iso-linoleic acid to flavour deterioration. PMID- 20285642 TI - Flavour reversion in hydrogenated linseed oil; further processing studies. PMID- 20285643 TI - Ration biscuits; effect of temperature and shortening type on keeping quality. PMID- 20285644 TI - Characteristics of Canadian lard. PMID- 20285646 TI - Thermal conductivity measurements on some New Zealand houses. PMID- 20285645 TI - Studies comparing the sanitizing efficiencies of hypochlorites and quaternary ammonium compounds. PMID- 20285647 TI - Biochemical research at Oxford upon mustard gas. PMID- 20285648 TI - Medical aspects of mustard gas poisoning. PMID- 20285650 TI - Discovery of molecular asymmetry. PMID- 20285649 TI - Edward Lhwyd; geologist, botanist and philologist (1660-1709). PMID- 20285651 TI - Ultra-violet absorption spectrum of anhydrous nitric acid. PMID- 20285652 TI - Structures of ethylene oxide and cyclopropane. PMID- 20285653 TI - Reactions of organic halides in solution. PMID- 20285654 TI - An optical-acoustic method of gas analysis. PMID- 20285655 TI - Effect of mono- and divalent salts on red blood cells. PMID- 20285656 TI - Effect of proteins on ketonaemia. PMID- 20285658 TI - BRITISH contribution to radiolocation. PMID- 20285659 TI - Crystallization of supersaturated solutions by means of electric current. PMID- 20285657 TI - Treatment of keratitis rosacea with small doses of testosterone. PMID- 20285660 TI - Luminescent decomposition of nitrous oxide. PMID- 20285661 TI - Stabilization of penicillin in aqueous solutions by low concentrations of phosphates. PMID- 20285662 TI - New substances exerting a combined bacteriostatic and respiration-inhibiting effect on tubercle bacilli. PMID- 20285663 TI - Influence of dl-methionine and other substances on the nephrotoxic action of dl serine. PMID- 20285664 TI - A mistaken symbiont of Oliarus cuspidatus. PMID- 20285665 TI - Helminth parasites of limpets. PMID- 20285666 TI - The nutritional significance of milk with special reference to milk sugar. PMID- 20285667 TI - Impressions of Japanese medicine at the end of World War II. PMID- 20285668 TI - Old age; minus and plus. PMID- 20285669 TI - Eskimo infanticide. PMID- 20285670 TI - Amino acids. PMID- 20285671 TI - Thomas Alva Edison. PMID- 20285672 TI - Contributions of entomology to theoretical biology. PMID- 20285673 TI - A case report on a history of scientific ideas. PMID- 20285674 TI - On life as a separate entity. PMID- 20285675 TI - Streptomycin. PMID- 20285676 TI - The staphylococci. PMID- 20285677 TI - Subdural haemorrhage, cysts and false membranes; illustrating the influence of intrinsic factors in disease when development of the body is normal. PMID- 20285678 TI - Fibre connections of the subthalamic region and the centro-median nucleus of the thalamus. PMID- 20285679 TI - Nutritional neuropathies in the civilian internment camp, Hong Kong, January, 1942-August, 1945. PMID- 20285680 TI - Meningitis carcinomatosa; a report of two cases. PMID- 20285681 TI - The ancestry of neuropathology; Hippocrates and De vulneribus capitis. PMID- 20285682 TI - Acute porphyria; report of a fatal case with severe neurologic manifestations encountered in the Southwest Pacific. PMID- 20285684 TI - Spondylitis rhizomyelique with extensive neurological manifestations; report of a case. PMID- 20285683 TI - Notes on the pathology of cranial tumors; the embryonal neoplasms; lipomas, dermoids, epidermoids (cholesteatomas), and chordomas. PMID- 20285685 TI - Circumscribed spinal arachnoiditis with cavitation of the spinal cord; report of a case. PMID- 20285686 TI - Cerebral abscess as a complication of meningomyelocele; report of two cases. PMID- 20285687 TI - Psychosomatic treatment of chronic headache. PMID- 20285688 TI - Bullet wound of the cervical part of the spinal cord; report of case of successful removal of bullet with partial functional return. PMID- 20285690 TI - Neuronitis and myasthenia gravis. PMID- 20285689 TI - Coccidioidal brain abscess. PMID- 20285691 TI - Delusion of body scheme due to subdural hematoma. PMID- 20285692 TI - Site of minimal lesion to produce coma. PMID- 20285693 TI - Thalamic lesions and coma. PMID- 20285694 TI - Riddoch's syndrome associated with disorientation in space and anomia. PMID- 20285695 TI - Etiology of idiopathic epilepsy. PMID- 20285696 TI - Intracranial complications of diseases of the eye and orbit. PMID- 20285697 TI - Cerebral malaria; review of the literature and report of case with residual symptoms indicative of cerebellar involvement. PMID- 20285698 TI - Calcification in ganglion cell tumors of the brain; review of the literature and report of a surgically verified case. PMID- 20285699 TI - Visual hallucinations as localizing manifestations of lesions of the temporal and occipital lobes; report of two illustrative cases with symptoms due to vascular malformations. PMID- 20285700 TI - A contribution to the study of sinus pericranii (Stromeyer); report of case with some comments on pathology of the lesion. PMID- 20285701 TI - Multiple gliomas; survey of the problem and report of three additional cases. PMID- 20285702 TI - Cerebellar subdural hydroma; report of an acute case following head injury. PMID- 20285703 TI - Treatment of epilepsy with hydantal, a new anti-convulsive drug; a preliminary report of its use in sixteen cases. PMID- 20285704 TI - Autotopagnosia and simultanagnosia with organic paranoid reaction. PMID- 20285705 TI - Denial of own blindness (Anton's syndrome); report of two cases, one with autopsy. PMID- 20285706 TI - A method of measuring tension in written documents. PMID- 20285707 TI - Value and need as organizing factors in perception. PMID- 20285708 TI - An analysis of predictions of delinquency based on case studies. PMID- 20285709 TI - Sex beliefs and practices among male college students. PMID- 20285710 TI - Diagnosing personality by the analysis of dreams. PMID- 20285711 TI - Beliefs in statements labeled fact and rumor. PMID- 20285712 TI - Ethical and political aspects of applied psychology. PMID- 20285713 TI - Specialists interpret the case of Harold Holzer. PMID- 20285714 TI - S. F., a case of homosexual panic. PMID- 20285715 TI - Playing the dozens. PMID- 20285717 TI - What makes attitudes and opinions liberal or conservative? PMID- 20285716 TI - The genetics of schizophrenia. PMID- 20285718 TI - Projection and the mote-beam-mechanism. PMID- 20285719 TI - [Not Available]. PMID- 20285720 TI - [Not Available]. PMID- 20285721 TI - [Not Available]. PMID- 20285722 TI - [Not Available]. PMID- 20285723 TI - [Not Available]. PMID- 20285724 TI - [Not Available]. PMID- 20285725 TI - [Not Available]. PMID- 20285726 TI - [Not Available]. PMID- 20285727 TI - [Not Available]. PMID- 20285728 TI - [Not Available]. PMID- 20285729 TI - [Not Available]. PMID- 20285730 TI - [Not Available]. PMID- 20285731 TI - [Not Available]. PMID- 20285732 TI - [Not Available]. PMID- 20285733 TI - Sensory ganglion cells within the central canal of the embryonic human spinal cord. PMID- 20285734 TI - The neocortex of Hapale. PMID- 20285735 TI - Retrograde degeneration of the thalamus following prefrontal lobotomy. PMID- 20285736 TI - Extracortical connections of the primate frontal cerebral cortex; thalamocortical connections. PMID- 20285737 TI - Ocular surgery; random observations. PMID- 20285738 TI - Malignant melanoma of limbus and spontaneous cyst of pigmented layer of iris in same sector; contribution to histogenesis of tumors. PMID- 20285739 TI - Atrophy of the optic nerve following hemorrhage. PMID- 20285740 TI - Treatment of lewisite burns of the eye with dimercaprol (BAL). PMID- 20285741 TI - Ocular changes in the blood dyscrasias. PMID- 20285742 TI - Ocular sporotrichosis; report of a case. PMID- 20285743 TI - A positive contact ball and ring implant for use after enucleation. PMID- 20285744 TI - An aid in facilitating postoperative dressing of the eye in patients with akinesis of lids. PMID- 20285745 TI - Cardinal points in aphakia. PMID- 20285746 TI - Permeability of the excised cornea. PMID- 20285747 TI - The production of a filtering cicatrix in glaucoma. PMID- 20285751 TI - Contributions to total blepharoplasty. PMID- 20285752 TI - The normal in the synoptophore. PMID- 20285753 TI - Lighting performance recommendations for portable and installed residence luminaires. PMID- 20285754 TI - The Munsell color system. PMID- 20285755 TI - The relation between illumination and vision. PMID- 20285756 TI - Integrated lighting for classrooms. PMID- 20285757 TI - Foot-candles for critical seeing. PMID- 20285758 TI - Practical color harmony with fluorescent light sources. PMID- 20285759 TI - Effect of external factors on light output of fluorescent sources. PMID- 20285760 TI - Studies of illumination and brightness in residential interiors. PMID- 20285761 TI - Ocular anomalies, service incurred. PMID- 20285762 TI - Clinical orthoptic procedure; minimum orthoptic examination methods for determining presence and degree of heterophorias. PMID- 20285763 TI - Color painting contrast in industry. PMID- 20285764 TI - OPTOMETRY in the Hoosier State. PMID- 20285765 TI - The mechanics of accommodation. PMID- 20285766 TI - Professional approach to the bifocal problem. PMID- 20285767 TI - Clinical orthoptic procedure; retinal correspondence and projection. PMID- 20285768 TI - Aids in squint measurement. PMID- 20285769 TI - The mechanics of accommodation. PMID- 20285770 TI - Prescribing tinted lenses. PMID- 20285771 TI - Objective observations and subjective findings with tangent cone lenses. PMID- 20285772 TI - Clinical orthoptic procedure; amblyopia. PMID- 20285773 TI - The mechanics of accommodation. PMID- 20285774 TI - A simple rapid method for assay of bactericidal and bacteriostatic agents. PMID- 20285775 TI - Studies of urobilinogen; further experience with the simple quantitative Ehrlich reaction; corrected calibration of the Evelyn colorimeter with a pontacyl dye mixture in terms of urobilinogen. PMID- 20285776 TI - The effect of lipids on Kahn antigen. PMID- 20285777 TI - The effect of lipids on Kahn antigen; increase of sensitivity by the addition of cephalin. PMID- 20285778 TI - Intraosseous infusions in infants. PMID- 20285779 TI - Effect of penicillin and antianthrax serum in experimental anthrax. PMID- 20285780 TI - Primary pulmonary vascular sclerosis; report of a case. PMID- 20285781 TI - Congenital pyloric stenosis; report of two cases in a family of three children. PMID- 20285782 TI - Electroencephalograms of infants and children with convulsive disorders. PMID- 20285783 TI - Examination of the infant and child. PMID- 20285784 TI - Myiasis; report of case. PMID- 20285785 TI - Laryngotracheobronchitis. PMID- 20285786 TI - Sexual maturation and the growth of fat, muscle and bone in girls. PMID- 20285787 TI - The speech behaviour of infants without families. PMID- 20285788 TI - The battle for a better Food and Drug Act. PMID- 20285789 TI - Use and misuse of hormones. PMID- 20285790 TI - The detoxication of pentavalent arsenicals. PMID- 20285791 TI - ACS; anti-reticular cytotoxic serum. PMID- 20285792 TI - Pharmaceutical research; the past and future. PMID- 20285793 TI - PYRIBENZAMINE and benadryl. PMID- 20285794 TI - USE and dispensing of streptomycin. PMID- 20285795 TI - NITROFURAN antiseptics. PMID- 20285796 TI - LOCAL use of penicillin. PMID- 20285797 TI - Thoughts on dispensing for dermatology. PMID- 20285798 TI - ENTEROGASTRONE: peptic ulcer hormone. PMID- 20285799 TI - Digitalis drugs. PMID- 20285801 TI - Pharmaceutical education. PMID- 20285800 TI - Will digitalis go? PMID- 20285802 TI - MEDICINE from the earth. PMID- 20285803 TI - LAVENDER. PMID- 20285804 TI - PHYSICIAN-GODS. PMID- 20285805 TI - The problem of the role of sulfhydryl enzymes in the mechanism of the action of certain chemotherapeutic agents. PMID- 20285806 TI - The assay of hydrastis and hydrastis preparations. PMID- 20285807 TI - PHENOTHIAZINE. PMID- 20285808 TI - THERAPEUTIC evaluation of National Formulary drugs. PMID- 20285809 TI - Determination of magnesium by precipitation with 8-hydroxyquinoline. PMID- 20285810 TI - The determination of aluminum in official drugs. PMID- 20285811 TI - Assay of cinchophen tablets. PMID- 20285812 TI - INFRA-RED radiation in pharmacy; a description of apparatus suitable for pharmaceutical and chemical processes using infra-red radiation as a source of heat. PMID- 20285814 TI - A new notation for organic chemistry. PMID- 20285813 TI - Modern aspects of surgical sutures. PMID- 20285815 TI - Recent developments in chromatography. PMID- 20285816 TI - Pharmacy in Sweden. PMID- 20285817 TI - SYNTHESIS of benzylpenicillin. PMID- 20285818 TI - A photoelectric colorimetric assay for digitoxin by comparison with a standard powder. PMID- 20285819 TI - Barbiturates; a blessing and a menace. PMID- 20285820 TI - Biologic assay of mercury ointments. PMID- 20285821 TI - Pharmaceutical applications of isoprophyl alcohol; solubilities of local anesthetics. PMID- 20285822 TI - The effect of serum and organ emulsions on penicillin fractions. PMID- 20285823 TI - The urinary excretion of penicillins G and K in rabbits. PMID- 20285824 TI - The effect of renal ligation on serum penicillin levels produced by penicillins G and K in rabbits. PMID- 20285825 TI - The determination of arsenic in official arsenicals. PMID- 20285826 TI - Comparison of several methods for the determination of arsenic in pentavalent arsenicals alone and in combination with bismuth. PMID- 20285827 TI - A study of the toxicity of two isomeric sodium hydroxymercuribenzoates. PMID- 20285828 TI - The effect of dimethylaminoethyl benzhydryl ether hydrochloride (benadryl) upon permeability of meningeal capillaries. PMID- 20285829 TI - The effect of amphetamine sulfate on performance of normal and fatigued subjects. PMID- 20285830 TI - The antidotal action of para-aminopropiophenone with or without sodium thiosulfate in cyanide poisoning. PMID- 20285831 TI - A quantitative method for the measurement of cigarette smoke irritation. PMID- 20285832 TI - The chronic toxicity and pathology of thiouracil in cats. PMID- 20285833 TI - Studies on the pharmacology of beta-diethylaminoethyldiphenylthioacetate, a synthetic antispasmodic. PMID- 20285834 TI - Digitalis; the Baljet reaction and pharmacodynamics of diginin. PMID- 20285835 TI - A method of screening sympathomimetic amines for stimulant action of the cerebrum. PMID- 20285836 TI - Studies in chemotherapy of tuberculosis; activity in vitro of a related series of ethers and arylamines. PMID- 20285837 TI - Pharmacological properties of a new adrenergic blocking agent: N,N-dibenzyl-beta chloroethylamine (dibenamine). PMID- 20285838 TI - Studies on the mechanism of action of thiourea and related compounds; the effect of acute poisoning on carbohydrate metabolism. PMID- 20285839 TI - The protective action of BAL in experimental antimony poisoning. PMID- 20285840 TI - Recent American drug and cosmetic novelties. PMID- 20285841 TI - Studies of modern synthetic emulgents; the chemistry of emulgents. PMID- 20285842 TI - The chemistry and pharmacy of capsicum. PMID- 20285843 TI - CHAULMOOGRA oil produced at Makogai Leper Colony. PMID- 20285844 TI - The esters and ethers of starch. PMID- 20285845 TI - Preservation by sodium benzoate and a method for its estimation. PMID- 20285846 TI - Studies of modern synthetic emulgents; conclusions and notes on formulation. PMID- 20285847 TI - ANTIBIOTICS; penicillin. PMID- 20285849 TI - The impact of pure science upon the chemical industry. PMID- 20285848 TI - The mineral supplement as a weapon against animal deficiency diseases. PMID- 20285850 TI - METHODS of air disinfection. PMID- 20285851 TI - The formulation of dental preparations. PMID- 20285852 TI - BRITAIN is slow in adopting a standard iodised salt. PMID- 20285853 TI - The war organisation of the German chemical industry. PMID- 20285854 TI - ANTIBIOTICS: streptomycin. PMID- 20285855 TI - ANTISEPTICS and disinfectants. PMID- 20285857 TI - THE diamidine compounds in therapeutic medicine. PMID- 20285856 TI - The sense of smell. PMID- 20285858 TI - Ultra-microscopic study of cosmetics. PMID- 20285859 TI - Paste and powder mixing. PMID- 20285860 TI - MOLECULAR weights of proteins. PMID- 20285861 TI - CASE for control of cosmetics. PMID- 20285862 TI - Production of synthetic menthols. PMID- 20285863 TI - Principles of tablet design. PMID- 20285865 TI - Spoilage caused by dormant bacterial spores. PMID- 20285864 TI - Methods of mineral supplementation and the formulation of mixes and bricks. PMID- 20285866 TI - Phenylmercuric nitrate and related compounds. PMID- 20285867 TI - SAFEGUARDS against fluorine hazards. PMID- 20285868 TI - U.S. cosmetic chemists make a progress report. PMID- 20285869 TI - ANTIBIOTICS including penicillin. PMID- 20285870 TI - The nature and treatment of allergy. PMID- 20285871 TI - Nails, their malformations and diseases. PMID- 20285872 TI - Recent developments in chromatography. PMID- 20285874 TI - COMMON cold; a long-term experiment. PMID- 20285873 TI - Modern aspects of surgical sutures. PMID- 20285875 TI - Standards of pharmacopoeial charcoal. PMID- 20285876 TI - Chapters in iodine's history. PMID- 20285877 TI - SYNTHESIS of penicillin. PMID- 20285878 TI - The action of iodine on the toxic and agglutinating factors of ricin. PMID- 20285879 TI - The determination of arsenic in organic arsenic compounds. PMID- 20285880 TI - The fruit of Lobelia inflata Linn. PMID- 20285881 TI - A study of the equilibria in solutions of neutral derivatives of sulphonamides. PMID- 20285882 TI - The stability of adrenaline solutions; storage of the proposed solution of adrenaline hydrochloride and injection of adrenaline tartrate. PMID- 20285883 TI - The estimation of progesterone in ethyl oleate solution. PMID- 20285884 TI - The determination of adulterants in drugs consisting of leaves. PMID- 20285885 TI - The disintegration of tablets. PMID- 20285886 TI - A disintegration test for tablets. PMID- 20285887 TI - Ipecacuanha; differential histological characters for the commercial varieties. PMID- 20285888 TI - The preparation of non-pyrogenic water and infusion fluids, using activated charcoal. PMID- 20285889 TI - Some aspects of penicillin stability. PMID- 20285890 TI - The stability of penicillin solutions. PMID- 20285891 TI - Indian squill and its differentiation from European squill. PMID- 20285892 TI - The colorimetric determination of morphine. PMID- 20285894 TI - The testing of drugs and pharmaceutical preparations for sterility; a new technique. PMID- 20285893 TI - The mixed alkaloids of Hyoscyamus muticus; a war-time application. PMID- 20285895 TI - A note on the effect of type of capillary glass on the melting-point of acetylsalicyclic acid. PMID- 20285897 TI - PITUITARY gonadotrophin. PMID- 20285896 TI - Riboflavine in malt extract. PMID- 20285898 TI - INTRACAINE. PMID- 20285899 TI - WHY pH? PMID- 20285900 TI - PROLONGING penicillin performance. PMID- 20285901 TI - FIELD for streptomycin. PMID- 20285902 TI - PROTEIN depletion. PMID- 20285903 TI - LUTEOTROPHIN. PMID- 20285905 TI - PROBLEM in absorption; slowing down penicillin. PMID- 20285904 TI - INFLUENZA immunisation in pediatric practice. PMID- 20285906 TI - CIRRHOSIS of the liver. PMID- 20285907 TI - DENTAL caries. PMID- 20285909 TI - MIGRAINE; new theories; new treatments. PMID- 20285908 TI - VITAMIN deficiency and neurosis. PMID- 20285910 TI - Endoscopy in cancer diagnosis. PMID- 20285911 TI - PELLAGRA and corn. PMID- 20285912 TI - ALLOXAN diabetes and its implications. PMID- 20285913 TI - VITAMIN K and delayed tonsillar hemorrhage. PMID- 20285914 TI - FOLIC ACID. PMID- 20285915 TI - VITAMIN D intoxication. PMID- 20285916 TI - BREATH without movement; a method for securing absolute rest for the lungs. PMID- 20285917 TI - STREPTOMYCIN in tularemia. PMID- 20285918 TI - Steady state fermentation by yeast in a growth medium. PMID- 20285919 TI - The action of various cations on muscle protoplasm. PMID- 20285920 TI - A comparative study of the effect of cyanide on the respiration of some Trypanosomidae. PMID- 20285921 TI - Action of mustard gas and other poisons on yeast cells; effect of mustard gas on the rate of cell division. PMID- 20285922 TI - Action of mustard gas and other poisons on yeast cells; effect of mustard gas on the mortality, morphology, carbohydrate metabolism, and permeability. PMID- 20285923 TI - Action of mustard gas and other poisons on yeast cells; distribution of fixed mustard gas in yeast. PMID- 20285924 TI - Determination of protein in serum and cerebrospinal fluid by formation of unimolecular films. PMID- 20285925 TI - The structure of trichocysts revealed by the electron microscope. PMID- 20285926 TI - Temperature effect upon rate of feeding in a folliculinid. PMID- 20285927 TI - The effect of certain deficient media on resting cyst formation in Colpoda duodenaria. PMID- 20285928 TI - Some interrelations of drug and ion actions in the artificial activation of marine eggs. PMID- 20285929 TI - The effects of certain denatured organs on neutralization in Amblystoma explants. PMID- 20285930 TI - The postnatal development of the reproductive system of the golden hamster (Cricetus auratus) and its reactivity to hormones. PMID- 20285931 TI - Interrelations of thyroid and gonad in the development of plumage and other sex characters in brown leghorn roosters. PMID- 20285933 TI - Phenomena that occur in the centrifuged eggs of the silkworm Bombyx mori L. PMID- 20285932 TI - Fission and disintegration in Stylaria fossularis at different temperatures. PMID- 20285934 TI - The effect of peanut oil on the desiccation of diapause and postdiapause pupae of the moth, Callosamia promethea Drury. PMID- 20285935 TI - Sensitization of the frog ovary following hypophysectomy. PMID- 20285936 TI - Oxygen consumption of lampreys, with special reference to metamorphosis and phylogenetic position. PMID- 20285937 TI - Pigmentation studies in salamanders, with especial reference to the changes at metamorphosis. PMID- 20285938 TI - Heat death, heat injury, and toxic factor. PMID- 20285939 TI - Studies on the nutrition of colorless euglenoid flagellates; growth of Astasia in an inorganic medium. PMID- 20285940 TI - The rate and site of acetate metabolism in the body. PMID- 20285941 TI - The colour sensitivity of the retina within the central fovea of man. PMID- 20285942 TI - The effect of limb position in seated subjects on their ability to utilize the maximum contractile force of the limb muscles. PMID- 20285943 TI - The ferricyanide method of blood-gas analysis. PMID- 20285944 TI - Experiments on liver sympathin. PMID- 20285945 TI - The action of chemical vesicants on cholinesterase. PMID- 20285947 TI - Arterial spasm in the human umbilical cord. PMID- 20285946 TI - Vitamin A and bone growth; the reversibility of vitamin A-deficiency changes. PMID- 20285948 TI - The tolerance of sheep to low concentrations of blood sugar. PMID- 20285949 TI - Effect of flavine-adeninedinucleotide and other substances on the synthesis of acetylcholine. PMID- 20285950 TI - Personality appraisal and the paranormal. PMID- 20285952 TI - Note on an impromptu experiment in psychokinesis. PMID- 20285951 TI - The psychology of the psychical researcher. PMID- 20285953 TI - Worker attitudes toward scheduling of industrial music. PMID- 20285954 TI - Analysis of two point-rating job evaluation plans. PMID- 20285955 TI - Correlation between scores on ortho-rater tests and clinical tests. PMID- 20285956 TI - Occupational differences in the Minnesota multiphasic personality inventory. PMID- 20285957 TI - The effect of an increasingly well defined criterion on the prediction of success at Naval Training School (Tactical Radar). PMID- 20285958 TI - Prediction of achievement in typewriting and stenography in a liberal arts college. PMID- 20285960 TI - Recombination of ideas in creative thinking. PMID- 20285959 TI - Readability of mixed type forms. PMID- 20285961 TI - Questionnaire and interview in neuropsychiatric screening. PMID- 20285962 TI - Restandardization of the revised beta examination to yield the Wechsler type of IQ. PMID- 20285963 TI - Oblique, second order, and cooperative factors in personality analysis. PMID- 20285964 TI - The vibratory sense. PMID- 20285965 TI - Laws of heredity in relation to general mental ability. PMID- 20285966 TI - Galen on the temperaments. PMID- 20285967 TI - Narcosis and visual contour clarity. PMID- 20285968 TI - The Ishihara test as a means of detecting and analyzing color vision. PMID- 20285969 TI - Some comparative data on differential pitch sensitivity under quantal and non quantal conditions. PMID- 20285970 TI - Dusky thinking. PMID- 20285971 TI - Professor Marc-Wogau's Theorie der Sinnesdata. PMID- 20285972 TI - The continental reception of Hume's treatise, 1739-1741. PMID- 20285974 TI - Second thoughts on causation, dualism, and interaction. PMID- 20285973 TI - The nervous system as physical machine; with special reference to the origin of adaptive behaviour. PMID- 20285975 TI - On the nature of fear. PMID- 20285976 TI - Expectation. PMID- 20285977 TI - The Gestalt view of the process of institutional transformation. PMID- 20285978 TI - Attitudes and learning; a methodical note. PMID- 20285979 TI - Communicative behavior. PMID- 20285980 TI - The hereditary differential in learning; a reply to F. A. Pattie. PMID- 20285981 TI - Symposium; the ego and the law of effect. PMID- 20285982 TI - The law of effect and ego psychology. PMID- 20285983 TI - Effect; a secondary principle of learning. PMID- 20285985 TI - Lamarckian-Darwinian reorientation. PMID- 20285984 TI - Technique for analysis of a highly generalized response pattern. PMID- 20285986 TI - Towards an experimental measure of personality. PMID- 20285987 TI - Brucellosis in the United States. PMID- 20285989 TI - Problems of an aging population; care of the aged and chronically ill. PMID- 20285988 TI - Problems of an aging population. PMID- 20285990 TI - Problems of an aging population; sheltered care of the aged. PMID- 20285992 TI - Problems of an aging population; public health aspects of diabetes. PMID- 20285991 TI - Problems of an aging population; preventive aspects of cancer control. PMID- 20285993 TI - Recent studies on disinfection of air in military establishments. PMID- 20285994 TI - A darkfield colony illuminator. PMID- 20285995 TI - Charts for counting bacterial colonies. PMID- 20285996 TI - Economic background to public health during the war. PMID- 20285997 TI - An outbreak of paratyphoid B fever in the nursery of a small hospital. PMID- 20285998 TI - Trichinosis in wild rats in Toronto. PMID- 20285999 TI - Public health nursing in the county health units of Quebec. PMID- 20286000 TI - Some aspects of sanitary food handling. PMID- 20286001 TI - Forty years of progress in the control of tuberculosis. PMID- 20286002 TI - Child dies of milk sick poisoning. PMID- 20286003 TI - Renewed interest in tuberculosis. PMID- 20286005 TI - Kitchen hygiene. PMID- 20286004 TI - Health and happiness in marriage. PMID- 20286006 TI - The parish pump [venereal disease control]. PMID- 20286007 TI - Social conditions and health education. PMID- 20286008 TI - Allergy in man. PMID- 20286009 TI - Permanent holiday camps for children. PMID- 20286010 TI - Social factors and mental health; puberty. PMID- 20286011 TI - Rural health units in Cyprus. PMID- 20286012 TI - An army experiment in sex education. PMID- 20286013 TI - Food education in a rural school. PMID- 20286014 TI - Ear, nose, and throat problems; present and future. PMID- 20286015 TI - One hundred years=m a retrospect and a forecast. PMID- 20286016 TI - The officer of health. PMID- 20286017 TI - The Peckham pioneer health centre. PMID- 20286019 TI - Smallpox. PMID- 20286018 TI - Handicapped pupils and disabled persons. PMID- 20286020 TI - The smallpox outbreak on Merseyside, 1946. PMID- 20286021 TI - The value of laboratory tests in the diagnosis of smallpox. PMID- 20286022 TI - The story of school dentistry. PMID- 20286023 TI - Typhoid fever. PMID- 20286024 TI - CANCER control. PMID- 20286025 TI - Relation of microscopic structure of laryngeal cancer to radiocurability. PMID- 20286026 TI - On roentgen examinations in head trauma. PMID- 20286027 TI - A new simplified radium applicator for intensifying the radiotherapy of the parametria in cancer of the cervix. PMID- 20286028 TI - Hernia diaphragmatica dextra; report of 2 cases. PMID- 20286029 TI - [Not Available]. PMID- 20286030 TI - A case of bend-formation in the colon, with closing of the intestine to passage of the contrast enema. PMID- 20286031 TI - Mediastinal phlebography. PMID- 20286032 TI - On roentgen diagnostics of adrenal tumours. PMID- 20286034 TI - Crossed renal ectopia. PMID- 20286033 TI - Fracture of the femoral neck following roentgen irradiation for cancer of the uterus. PMID- 20286035 TI - Hypertrophy of the pylorus in adults. PMID- 20286037 TI - The radiological diagnosis of lipomata. PMID- 20286036 TI - Standardised radiological pelvimetry; quantitative aspects. PMID- 20286038 TI - A thickness technique in radiographic examinations of the abdomen and pelvis. PMID- 20286039 TI - Tuberculous cystitis; notes on three cases. PMID- 20286041 TI - The determination of X-ray energy distributions by the absorption method. PMID- 20286040 TI - The effect of gamma radiation on mitosis in vitro. PMID- 20286042 TI - Provisional calculation of the tolerance flux of thermal neutrons. PMID- 20286043 TI - PHYSICIST The danger from scattered radiation; a further comment. PMID- 20286044 TI - Danger from scattered radiation; a criticism. PMID- 20286045 TI - Reverse-position radiography. PMID- 20286047 TI - Radiographic exposures. PMID- 20286046 TI - Myelography. PMID- 20286048 TI - [Not Available]. PMID- 20286049 TI - [Not Available]. PMID- 20286050 TI - [Not Available]. PMID- 20286051 TI - [Not Available]. PMID- 20286052 TI - [Not Available]. PMID- 20286053 TI - [Not Available]. PMID- 20286055 TI - [Not Available]. PMID- 20286054 TI - [Not Available]. PMID- 20286056 TI - [Not Available]. PMID- 20286057 TI - [Not Available]. PMID- 20286058 TI - [Not Available]. PMID- 20286059 TI - [Not Available]. PMID- 20286060 TI - [Not Available]. PMID- 20286061 TI - [Not Available]. PMID- 20286062 TI - [Not Available]. PMID- 20286063 TI - [Not Available]. PMID- 20286065 TI - [Not Available]. PMID- 20286064 TI - [Not Available]. PMID- 20286066 TI - [Not Available]. PMID- 20286067 TI - [Not Available]. PMID- 20286068 TI - [Not Available]. PMID- 20286069 TI - [Not Available]. PMID- 20286070 TI - [Not Available]. PMID- 20286071 TI - [Not Available]. PMID- 20286072 TI - [Not Available]. PMID- 20286073 TI - [Not Available]. PMID- 20286074 TI - Effect of estrogenic hormone on advanced carcinoma of the female breast. PMID- 20286075 TI - Patent omphalomesenteric duct and its relation to the diverticulum of Meckel. PMID- 20286076 TI - Granulomas caused by surgical silk and cotton sutures. PMID- 20286077 TI - Strangulated inguinal hernia; observations in fifty cases. PMID- 20286078 TI - Gastric ulcers produced experimentally by vascular ligation. PMID- 20286079 TI - Tuberculous dactylitis in the adult. PMID- 20286080 TI - Method of correction of ectopia cordis. PMID- 20286081 TI - Diseases of growing and adult bone. PMID- 20286082 TI - Congenital deformities. PMID- 20286084 TI - [Not Available]. PMID- 20286083 TI - Tumors of bone and of synovial membrane. PMID- 20286085 TI - [Not Available]. PMID- 20286086 TI - [Not Available]. PMID- 20286087 TI - [Not Available]. PMID- 20286088 TI - [Not Available]. PMID- 20286089 TI - [Not Available]. PMID- 20286090 TI - [Not Available]. PMID- 20286091 TI - [Not Available]. PMID- 20286092 TI - [Not Available]. PMID- 20286093 TI - [Not Available]. PMID- 20286094 TI - [Not Available]. PMID- 20286095 TI - [Not Available]. PMID- 20286096 TI - [Not Available]. PMID- 20286097 TI - [Not Available]. PMID- 20286098 TI - [Not Available]. PMID- 20286099 TI - Surgical thoracic tumors in Navy personnel. PMID- 20286100 TI - The Chest Tumor Registry. PMID- 20286101 TI - A report of 196 lobectomies performed at Kennedy General Hospital Chest Surgical Center from 1943 to 1946 with one death. PMID- 20286102 TI - A follow-up study of the cardiopulmonary function in four young individuals after pneumonectomy. PMID- 20286103 TI - The use of curare in anesthesia for thoracic surgery. PMID- 20286104 TI - Surgical treatment of myasthenia gravis. PMID- 20286105 TI - Aerosol penicillin as a therapeutic adjunct in the preparation of patients with suppuration of the lung for pulmonary resection. PMID- 20286106 TI - Anesthesia for thoracic surgery in the United States Army. PMID- 20286107 TI - Protein deficiency in surgical patients. PMID- 20286108 TI - Newer concepts of the pathologic physiology of shock; peripheral circulatory collapse. PMID- 20286109 TI - Fluid, electrolyte and nutritional problems in surgery. PMID- 20286110 TI - Some aspects of nutrition in man. PMID- 20286112 TI - Circulatory changes during spinal anesthesia: their physiological basis. PMID- 20286111 TI - Circulatory physiology; the adjustment to blood loss and postural changes. PMID- 20286113 TI - Venous thrombosis and pulmonary embolism. PMID- 20286114 TI - The healing of wounds. PMID- 20286115 TI - The pathologic physiology of infection. PMID- 20286116 TI - Physiological principles in intestinal obstruction. PMID- 20286117 TI - Certain physiological problems pertaining to thoracic surgery. PMID- 20286118 TI - The pathologic physiology of hyperthyroidism. PMID- 20286119 TI - Pathologic physiology of hyperparathyroidism. PMID- 20286120 TI - The healing of fractures. PMID- 20286121 TI - Pathologic physiology of prostatic obstruction. PMID- 20286122 TI - The pathologic physiology of the extensive superficial burn. PMID- 20286123 TI - Metabolic disturbances simulating acute abdominal emergencies. PMID- 20286124 TI - The surgical treatment of chronic infected pilonidal sinus. PMID- 20286125 TI - The clinical course of yaws in Lango, Uganda. PMID- 20286126 TI - Atebrin susceptibility of the Aitaipe-Wewak strains of P. falciparum and P. vivax; a field and experimental investigation by L. H. Q. Medical Research Unit, Cairns. PMID- 20286127 TI - Control of plague by means of live avirulent plague vaccine in Southern Africa (1941-44). PMID- 20286128 TI - Transmission of dengue fever by Aedes (Stegomyia) scutellaris Walk. in New Guinea. PMID- 20286129 TI - The aetiology of desert sore. PMID- 20286130 TI - Heterophile antibodies in trypanosomiasis. PMID- 20286131 TI - Tsetse fly repellents. PMID- 20286132 TI - Growth of protozoa in tissue culture; Trypanosoma cruzi. PMID- 20286133 TI - Kaposi's multiple idiopathic haemorrhagic sarcoma. PMID- 20286134 TI - A simple device for the application of DDT larvicide. PMID- 20286135 TI - A case of blackwater fever during mepacrine therapy. PMID- 20286136 TI - Heart disease in the case-finding program. PMID- 20286137 TI - Cancer and pulmonary tuberculosis; diagnostic problems in patients with cancer of the lung in the presence of pulmonary tuberculosis. PMID- 20286138 TI - Cytology of bronchial secretions; a diagnostic aid in the diagnosis of pulmonary tuberculosis. PMID- 20286139 TI - Pneumothorax fluid; its management by systematic aspiration. PMID- 20286140 TI - Cholesterol pleural effusion. PMID- 20286141 TI - Extrapleural pneumothorax in silico-tuberculosis. PMID- 20286142 TI - Tuberculosis; a labor problem. PMID- 20286143 TI - Mass miniature radiography; a survey in the United States Army Air Forces. PMID- 20286144 TI - Serial tuberculin tests and stability of the tuberculin reaction. PMID- 20286145 TI - Certain effects of streptomycin on mycobacteria in vitro. PMID- 20286146 TI - Synthesis of B-complex vitamins by tubercle bacilli when grown on synthetic media. PMID- 20286147 TI - The relationship of acquired resistance, allergy, antibodies and tissue reactivities to the components of the tubercle bacillus. PMID- 20286148 TI - Respiratory patterns in pulmonary tuberculosis. PMID- 20286149 TI - On the etiology of sarcoidosis. PMID- 20286150 TI - The technique and standardisation of radiographs of tuberculosis of the chest. PMID- 20286151 TI - Broncho-stenosis in pulmonary tuberculosis; a problem in treatment. PMID- 20286152 TI - The treatment of tension cavities. PMID- 20286153 TI - Pulmonary tuberculosis; effect of sea voyage on 37 unselected cases. PMID- 20286154 TI - On selecting treatment for the patient with pulmonary tuberculosis. PMID- 20286155 TI - Familial eunuchoidism; the Laurence-Moon-Biedl syndrome. PMID- 20286157 TI - Unilateral renal tuberculosis; management of the nephrectomized patient; review of ninety-eight cases. PMID- 20286156 TI - Adenoma of the kidney. PMID- 20286158 TI - Large hydronephrosis of a true supernumerary kidney. PMID- 20286159 TI - Hypertension associated with solitary renal cyst; report of two cases. PMID- 20286160 TI - Stones in the ureter; their extraction by looped catheter. PMID- 20286161 TI - Misinterpretations of enlarged prostates gained through cystoscopy. PMID- 20286162 TI - Infarct of the prostate. PMID- 20286163 TI - Carcinoma of the prostate; simultaneous occurrence in identical twins. PMID- 20286164 TI - Care of the paraplegic's urinary tract. PMID- 20286165 TI - Sperm invasion of the epididymis. PMID- 20286166 TI - Aneurysms involving the urinary tract. PMID- 20286167 TI - Modification of the Bumpus forceps. PMID- 20286168 TI - Azoospermia; an analysis of 146 cases. PMID- 20286169 TI - Solitary polycystic kidney and successful pregnancy. PMID- 20286170 TI - The management of ureteropelvic juncture obstruction; translumbar aortography an adjunct. PMID- 20286171 TI - Cancer cells in prostatic secretions. PMID- 20286172 TI - An operation for the cure of certain cases of plastic induration (Peyronie's disease) of the penis. PMID- 20286173 TI - Bilateral calcified testicular gumma. PMID- 20286174 TI - Anomalies associated with undescended testis; complete separation of a partly descended epididymis and vas deferens and an abdominal testis. PMID- 20286175 TI - A new visual system for observation and operation in the urinary bladder. PMID- 20286176 TI - Clinical cystometrogram. PMID- 20286177 TI - Streptomycin therapy in urinary tract infections. PMID- 20286178 TI - The teaching of urology to residents in a large general hospital. PMID- 20286179 TI - MEXICAN outbreak of foot-and-mouth disease. PMID- 20286180 TI - Muscular dystrophy (white muscle disease) in young calves. PMID- 20286181 TI - Panel discussion on artificial insemination of cows. PMID- 20286182 TI - Brucellosis in swine; field control experiments. PMID- 20286183 TI - Present status of streptomycin. PMID- 20286184 TI - Raising heifer calves on mastitis milk. PMID- 20286185 TI - Possible use of an arsenical compound in the treatment of heartworm in dogs. PMID- 20286186 TI - Sterility in cattle. PMID- 20286187 TI - Neoplasms of animals; their clinical importance and treatment. PMID- 20286188 TI - Canine spirochetosis. PMID- 20286189 TI - Cattle fever ticks in Florida. PMID- 20286190 TI - Studies in immunity. PMID- 20286191 TI - Some common nervous ailments in dogs. PMID- 20286192 TI - Veterinary education in the Southeast. PMID- 20286193 TI - Anaerobic spores in sulfanilamide powder. PMID- 20286194 TI - Bilateral fractures in dog. PMID- 20286195 TI - Orchitis in a bull. PMID- 20286196 TI - Cryptorchid on a cat. PMID- 20286197 TI - Tetanus in a dog. PMID- 20286199 TI - Chemical, physical and immunological properties of electrophoretically purified pollen extracts. PMID- 20286198 TI - Bacterial allergy. PMID- 20286200 TI - Report on the standardization of dust extracts. PMID- 20286201 TI - Clinical and comparative allergy. PMID- 20286202 TI - Hay-fever plants of Albuquerque, New Mexico; a preliminary report. PMID- 20286203 TI - Pediatric allergy; a critical review of recent literature. PMID- 20286204 TI - Reactions to antipneumococcal rabbit serum. PMID- 20286205 TI - Delayed absorption of proteins in the guinea pig. PMID- 20286206 TI - Quantitative changes in various fractions of the precipitable nitrogen in ragweed extracts during incubation (37 degrees C.). PMID- 20286207 TI - Sensitization by topical application of sulfonamides. PMID- 20286208 TI - Effective treatment of extremely sensitive hay fever patients by the chilling method. PMID- 20286209 TI - Penicillin in intractable asthma. PMID- 20286210 TI - Etiologic evaluation of asthma in 100 cases returned from overseas. PMID- 20286211 TI - Immunochemistry; a review intended especially for students of allergy. PMID- 20286212 TI - Morphology of the feet in polydactyl cats. PMID- 20286213 TI - Histology of the moderator band in man and other mammals with special reference to the conduction system. PMID- 20286214 TI - On the development, morphology and interpretation of a system of crypt-analogues in the pharyngeal tonsil. PMID- 20286215 TI - Adult human sympathetic ganglion cells cultivated in vitro. PMID- 20286216 TI - Implantation of the rat egg; alteration in osmiophilic epithelial lipids of the rat uterus under normal and experimental conditions. PMID- 20286217 TI - The block-surface method of staining as applied to the study of embryology. PMID- 20286218 TI - A simple method for making permanent, differentially stained preparations of small nerve plexuses. PMID- 20286219 TI - A transparent chamber for the observation of the pancreas of the living mouse. PMID- 20286220 TI - Permanent dry preparations of cartilage and bone; a method especially applicable to fetal material. PMID- 20286221 TI - The cervix uteri of the rat. PMID- 20286222 TI - Mitotic division and degeneration of lymphocytes within cells of intestinal epithelium in young and in adult white mice. PMID- 20286223 TI - Reaction of the digoxin-injured myocardium of rats and mice to vital dyes. PMID- 20286224 TI - Description of bilateral coraco-brachialis brevis muscle, with a note on its significance. PMID- 20286225 TI - Studies on the parathyroid of the mouse; some observations upon the post-natal cytological development of the normal gland, with particular reference to its mitotic activity and Golgi elements. PMID- 20286226 TI - Radial hemimelia and the functional anatomy of the carpus. PMID- 20286227 TI - The plane of fracture of the caudal vertebrae of certain lacertilians. PMID- 20286228 TI - Spiral nerve endings in the extrinsic eye muscles of man. PMID- 20286229 TI - Development of the egg of the cow up to the stage of blastocyst formation. PMID- 20286230 TI - A new silver method for staining paraffin sections of the nervous system. PMID- 20286231 TI - A technique for the preservation of animals for the study of joint movement and for routine dissection. PMID- 20286232 TI - Patent foramen ovale and ductus arteriosus in a lion club. PMID- 20286233 TI - The laxator tympani muscle. PMID- 20286234 TI - A previllous human embryo. PMID- 20286235 TI - A pseudo-hermaphrodite. PMID- 20286236 TI - Remnants of left truncus transversus in injected human foetuses. PMID- 20286237 TI - Principles of growth and repair in membrane bones. PMID- 20286238 TI - Intrauterine death and its consequences in the rat. PMID- 20286239 TI - Abnormal cervical vertebrae report of two cases. PMID- 20286240 TI - Dissection of the human atrioventricular bundle. PMID- 20286241 TI - The storage of vital stains (trypan blue, vital new red) in the rabbit endocardium. PMID- 20286242 TI - The interlabor approach to the roots of the lungs. PMID- 20286243 TI - The morphology and function of mammalian digital sesamoid bones. PMID- 20286244 TI - Pronation and supination in tetrapods. PMID- 20286245 TI - The reputed hormone of semen. PMID- 20286246 TI - Crossed and uncrossed optic fibres of the dog. PMID- 20286247 TI - Factors influencing hair-growth rhythm. PMID- 20286248 TI - Vital staining of the reticulum and lymphoid tissue of the rabbit appendix. PMID- 20286249 TI - Further observations on the regeneration of muscle tissue. PMID- 20286250 TI - Stimulation of new bone production. PMID- 20286251 TI - Cauda humana in a Tamil. PMID- 20286252 TI - The pattern of olfactory innervation. PMID- 20286253 TI - Fibre connexions of the subthalamic region. PMID- 20286255 TI - Congenital absence of ventrolateral abdominal musculature. PMID- 20286254 TI - The formation of birefringent crystals in the suprarenal cortex. PMID- 20286256 TI - Hydatiform degeneration in an early human embryo. PMID- 20286257 TI - The height of the eustachian valve correlated with the direction of the (right) anterior caval blood flow. PMID- 20286258 TI - Edwin Stephen Goodrich, 1868-1946. PMID- 20286259 TI - Studies on the structure, development, and physiology of the nephridia of Qligochaeta; biochemical estimations of nutritive and excretory substances in the blood and coelomic fluid of the earthworm and their bearing on the role of the two fluids in metabolism. PMID- 20286260 TI - The effect of the removal of the lateral appendix in the embryonic olfactory organ of Kaloula borealis (Barbour). PMID- 20286261 TI - The effect of removal of the anterior lower sac on the lateral appendix in the embryonic olfactory organ of Kaloula borealis (Barbour). PMID- 20286262 TI - The formation and structure of the chorion of the egg in an hemipteran, Rhodnius prolixus. PMID- 20286263 TI - The histochemical recognition of lipine. PMID- 20286264 TI - Refrigeration in the treatment of trauma, with review of crymotherapy. PMID- 20286265 TI - Spinal anesthesia; the protector of the baby in cesarean sections. PMID- 20286266 TI - Anesthesia for oropharyngeal surgery. PMID- 20286267 TI - Intramuscular pentobarbital sodium and benzyl alcohol as a preanesthetic agent. PMID- 20286268 TI - The use of curare to lessen anesthetic hazards. PMID- 20286269 TI - Oral surgery anesthesia; safer and more profound. PMID- 20286270 TI - Cyclopropane ether anesthesia. PMID- 20286271 TI - A contribution to the pharmacodynamics and therapeutics of acetyl-5 bromosalicylic acid. PMID- 20286272 TI - Refrigeration in the treatment of trauma, with review of crymotherapy; use of refrigeration to minimize the ill effects of tourniquets. PMID- 20286273 TI - General anesthesia and analgesia for dental and oral surgery. PMID- 20286274 TI - The anesthetic of transthoracic vagotomy. PMID- 20286275 TI - Heart disease, anesthesia and surgery. PMID- 20286276 TI - A new Army Medical Library. PMID- 20286277 TI - An insecticidal check method for measuring the efficacy of entomophagous insects. PMID- 20286278 TI - Salt marsh and anopheline mosquito control by ground dispersal of DDT aerosols. PMID- 20286279 TI - Particle size of insecticides and its relation to application, distribution, and deposit. PMID- 20286280 TI - DDT used to control a rice-field mosquito, Psorophora confinnis. PMID- 20286281 TI - Cub airplanes in the South Pacific for application of DDT. PMID- 20286282 TI - Development of spraying apparatus for HNS-1 helicopter. PMID- 20286283 TI - DDT-xylene emulsions for use against insects affecting man. PMID- 20286284 TI - DDT to control maggots in latrines. PMID- 20286285 TI - Control of fly larvae in simulated pit latrines and in carcasses. PMID- 20286286 TI - DDT used to control flies in Manila. PMID- 20286287 TI - Effects of DDT on the body louse. PMID- 20286288 TI - Further tests of the more promising materials against the body louse. PMID- 20286289 TI - Flea repellents for use on clothing. PMID- 20286290 TI - An oil-DDT vapor spray to control grape leaf-hopper. PMID- 20286291 TI - The effect of sublethal dosages of tartar emetic on the Mexican fruitfly. PMID- 20286292 TI - Soil insecticides for control of the Southern corn rootworm. PMID- 20286294 TI - Sunflower seed weevils and their control. PMID- 20286293 TI - Effect of xanthone, DDT, and other insecticides on the Pacific mite. PMID- 20286295 TI - Effect of lead arsenate sprays on the pecan weevil and other pecan insects. PMID- 20286296 TI - Sub-soil bark injury from kerosene spray. PMID- 20286297 TI - Feeding experiments with DDT-treated pea vine silage with special reference to dairy cows, sheep, and laboratory animals. PMID- 20286298 TI - DDT residues on pea vines and canned peas from fields treated with DDT dusts. PMID- 20286299 TI - Repellent properties of extract of Amorpha fruticosa. PMID- 20286300 TI - Hexaethyl tetraphosphate for control of mites. PMID- 20286301 TI - Di(4, chlorophenoxy) methane for control of citrus red mite. PMID- 20286302 TI - A new host for Cybocephalus sp., a predator of diaspine Coccidae. PMID- 20286303 TI - Effect of hexachlorocyclohexane on onion seedlings. PMID- 20286304 TI - Benzene hexachloride as an ovicide for the short-nosed ox louse. PMID- 20286305 TI - Controlling the fall armyworm in sweet corn and popcorn with DDT. PMID- 20286306 TI - Laboratory tests in controlling pillbugs. PMID- 20286307 TI - Detrimental effect of rotenone on Rodolia cardinalis. PMID- 20286308 TI - Effect of oil sprays on resistance of California red scale to HCN fumigation. PMID- 20286309 TI - The use of leaf tissue in graft-transmission of psorosis virus. PMID- 20286310 TI - A chemical study of the mycelium and sclerotia of Phymatotrichum omnivorum. PMID- 20286311 TI - Influence of certain environmental conditions on chlorotic streak of sugar cane. PMID- 20286312 TI - The effect of seedling diseases of castor beans on the subsequent plant development and yield. PMID- 20286313 TI - A fungicide for protecting lily bulbs from infection by Golletotrichum lilii. PMID- 20286314 TI - The effects of carborundum in inoculating bean plants with bacteria. PMID- 20286316 TI - Studies on fermentation in rice and barley. PMID- 20286315 TI - The response of normal plant tissues and of crown-gall tumor tissues to synthetic growth hormones. PMID- 20286317 TI - Embryogeny and the development of the apical meristoms of Pseudotsuga; late embryogeny. PMID- 20286318 TI - On the reproduction of some Pacific Coast species of Ulva. PMID- 20286319 TI - The influence of nutrition on Fusarium basal rot of narcissus and on Fusarium yellows of gladiolus. PMID- 20286320 TI - Observations on chytridiaceous parasites of phanerogams; a preliminary study of the occurrence of ephemeral sporangia in the Physoderma disease of maize. PMID- 20286321 TI - Studies on Oscinella frit Linn.; notes on the resistance of cereals to infestation. PMID- 20286322 TI - A survey of potato aphides in north-west Derbyshire, 1945. PMID- 20286323 TI - The assimilation of ammonium and nitrate nitrogen by detached potato sprouts. PMID- 20286324 TI - The formation of insecticidal films on building materials; preliminary experiments with films of pyrethrum and DDT in a heavy oil. PMID- 20286325 TI - A note on the efficiency of a pyrethrum spray in controlling Ephestia elutella Hb. moths in a granary. PMID- 20286326 TI - The use of toxic polynitro derivatives in pest control; the stability of dinitro o-cresol in compounded products. PMID- 20286327 TI - Studies upon the copper fungicides; investigations with the exudate from fungus spores. PMID- 20286328 TI - Field trials of copper fungicides for the control of potato blight; low-copper fungicides. PMID- 20286329 TI - The influence of potato variety on the cyst of the potato-root eelworm, Heterodera rostochiensis Wollenweber. PMID- 20286330 TI - A note on the relation of nematodes (Tylenchus tritici) to the development of the bacterial disease of wheat caused by Bacterium tritici. PMID- 20286331 TI - A mosaic disease of cowpea Vigna sinensis Endl. PMID- 20286332 TI - Cultivation of animal tissues in vitro in nutrients of precisely known constitution. PMID- 20286333 TI - On trephocytes and trephocytosis; a study on the role of leucocytes in nutrition and growth. PMID- 20286334 TI - The influence of diet on mitotic division in the intestinal epithelium of the mouse. PMID- 20286335 TI - [Not Available]. PMID- 20286336 TI - Tolerance of larvae of Drosophila for amino acids; methionine, cystine and cysteine. PMID- 20286337 TI - The combined effect of colchicine and X-rays on the growth of Allium cepa seeds. PMID- 20286339 TI - The mechanism of fertilization of eggs. PMID- 20286338 TI - Nitrate and phosphate vs. L-proline as factors in the behaviour of Ulva. PMID- 20286340 TI - The epithelioneural bodies. PMID- 20286341 TI - The roles of motile larvae and fixed adults in the origin of the vertebrates. PMID- 20286342 TI - Physical medicine in the treatment of rheumatoid arthritis with associated xanthomas. PMID- 20286343 TI - Sciatica. PMID- 20286344 TI - The present position of the treatment of spondylitis. PMID- 20286345 TI - The mechanism of oral infection in arthritis. PMID- 20286346 TI - Rheumatism. PMID- 20286347 TI - Pulmonary (venous) air embolism. PMID- 20286348 TI - The heart in uremia; an electrocardiographic and pathologic study. PMID- 20286349 TI - Sequence of ventricular stimulation and contraction in a case of anomalous atrioventricular excitation. PMID- 20286350 TI - The volume elasticity of the aorta in the intact dog. PMID- 20286351 TI - The diagnosis and treatment of thromboangiitis obliterans in the vascular centers of Army general hospitals. PMID- 20286352 TI - The influence of vitamin B1 deficiency on the pyruvate exchange of the heart. PMID- 20286353 TI - Pathology of the mitral valve in the older age groups. PMID- 20286354 TI - Congenital paroxysmal tachycardia; report of a case recognized ante partum. PMID- 20286355 TI - Diffuse scleroderma with involvement of the heart; report of a case. PMID- 20286356 TI - Multiple liver abscesses with rupture into the pericardium. PMID- 20286357 TI - [Not Available]. PMID- 20286358 TI - [Not Available]. PMID- 20286360 TI - [Not Available]. PMID- 20286359 TI - [Not Available]. PMID- 20286361 TI - [Not Available]. PMID- 20286362 TI - [Not Available]. PMID- 20286363 TI - [Not Available]. PMID- 20286364 TI - [Not Available]. PMID- 20286365 TI - [Not Available]. PMID- 20286366 TI - [Not Available]. PMID- 20286367 TI - [Not Available]. PMID- 20286368 TI - [Not Available]. PMID- 20286369 TI - [Not Available]. PMID- 20286370 TI - [Not Available]. PMID- 20286371 TI - [Not Available]. PMID- 20286373 TI - [Not Available]. PMID- 20286372 TI - [Not Available]. PMID- 20286374 TI - [Not Available]. PMID- 20286375 TI - [Not Available]. PMID- 20286376 TI - [Not Available]. PMID- 20286377 TI - [Not Available]. PMID- 20286378 TI - [Not Available]. PMID- 20286379 TI - The estimation of 2:2-bis-(p-chlorophenyl)-l:1:l-trichloroethane (p,p'-DDT) by methods depending on its dehydrohalogenation. PMID- 20286380 TI - The estimation of traces of mercury in urine. PMID- 20286381 TI - The estimation of mercury compounds in the atmosphere. PMID- 20286382 TI - The precipitation of aluminium and its separation from cobalt, chromium, nickel or zinc by means of ammonium benzoate. PMID- 20286383 TI - The determination of copper and arsenic in iron pyrites by the method of internal electrolysis. PMID- 20286384 TI - A note on alcohol in blood and urine. PMID- 20286386 TI - Molecular-weight determination by light scattering. PMID- 20286385 TI - The cellulose molecule; physical-chemical studies. PMID- 20286387 TI - The association of polymer molecules in dilute solution. PMID- 20286388 TI - Viscosity-molecular relationship for cellulose acetate. PMID- 20286389 TI - Elasticity measurements on polychloroprenes. PMID- 20286390 TI - A statistical theory of discoloration for halogen-containing polymers and copolymers. PMID- 20286391 TI - Ultracentrifugal and viscometric studies of amylose acetates; further evidence for the helical structure of amylose. PMID- 20286392 TI - Effect of molecular association and charge distribution on the gelatin of pectin. PMID- 20286393 TI - Molecular properties of hemicellulose fractions. PMID- 20286394 TI - Sedimentation constants of purified preparations of strains of influenza virus. PMID- 20286395 TI - On a low-density lipoprotein appearing in normal human plasma. PMID- 20286396 TI - Ultracentrifugal and electrophoretic studies on fetuin. PMID- 20286397 TI - The quantitative interpretation of the electrophoretic patterns of proteins. PMID- 20286398 TI - Physical-chemical characteristics of certain of the proteins of normal human plasma. PMID- 20286399 TI - Multiple protein interactions as exhibited by the blood-clotting mechanism. PMID- 20286400 TI - Hemocyanins of the gastropods. PMID- 20286401 TI - Physicochemical characterization of pituitary growth hormone. PMID- 20286402 TI - Mandelate as a stabilizer of serum albumin. PMID- 20286403 TI - Diffusion in wood. PMID- 20286404 TI - Micelle structure in aqueous solutions of colloidal electrolytes. PMID- 20286405 TI - The morphology of lyogels. PMID- 20286406 TI - Solubilization of water-insoluble dye by pure soaps and detergents of different types. PMID- 20286407 TI - The electrochemistry of permselective collodion membranes; experimental studies on the concentration potential across various types of permselective collodion membranes with solutions of several electrolytes. PMID- 20286409 TI - The electrokinetic potentials of precipitates. PMID- 20286408 TI - The colloid chemistry of the clay mineral attapulgite. PMID- 20286410 TI - The effect of heat-treatment on the sorption-desorption hysteresis characteristics of silica gel. PMID- 20286411 TI - The equilibrium spreading coefficient of amphipathic organic liquids on water. PMID- 20286412 TI - A kinetic study of the urea-formaldehyde reaction. PMID- 20286413 TI - Aniline formate and its changes on keeping. PMID- 20286414 TI - Solubility and melting point as functions of particle size; the induction period of crystallization. PMID- 20286415 TI - Rates of solution of soaps in water. PMID- 20286416 TI - Bond energy in diatomic molecules from the force constants, nuclear distances, and classical model theory. PMID- 20286417 TI - Effect of freezing on the stability of colloidal dispersions; silica sols; a preliminary report. PMID- 20286418 TI - Coordination compounds of boron trichloride; systems with the propyl chlorides. PMID- 20286419 TI - The rise of air bubbles in lubricating oils. PMID- 20286420 TI - Energy additivity in oxygen-containing crystals and glasses. PMID- 20286421 TI - Stability of synthetic rubber dispersions; low-temperature thickening of neoprene latex. PMID- 20286422 TI - Stability of synthetic rubber dispersions; coagulation of neoprene latices by freezing. PMID- 20286423 TI - A spectroturbidimetric study of the proteins of milk. PMID- 20286424 TI - Notes on dynamic osmometry. PMID- 20286425 TI - Vapor pressure and heat of vaporization of acetylmethylcarbinol. PMID- 20286427 TI - Dimensional stabilization of wood. PMID- 20286426 TI - Studies on the aging of precipitates and coprecipitation; the compressibility of silver bromide powders. PMID- 20286428 TI - Kinetics of homogeneous gaseous reactions in flow systems. PMID- 20286429 TI - On unimolecular reactions and radioactive transformations. PMID- 20286430 TI - Isotonic solutions; osmotic and activity coefficients of lithium and sodium perchlorates at 25 degrees C. PMID- 20286431 TI - X-ray diffraction studies in the system Fe2O3-Cr2O3. PMID- 20286432 TI - The Antoine vapor-pressure equation for mononuclear aromatic hydrocarbons. PMID- 20286434 TI - Cavitation from solid surfaces in the absence of gas nuclei. PMID- 20286433 TI - A mathematical approach to reaction mechanisms. PMID- 20286435 TI - An unusual liquid interface. PMID- 20286436 TI - Molecular properties of nitrocellulose; studies of viscosity. PMID- 20286437 TI - Molecular properties of nitrocellulose; studies of molecular heterogeneity. PMID- 20286438 TI - The thermochemistry of propellent explosives. PMID- 20286439 TI - Determination of the heat of combustion of nitroglycerin and the thermochemical constants of nitrocellulose. PMID- 20286440 TI - Radiation chemistry. PMID- 20286441 TI - The effect of temperature on the intensity of X-ray reflexion. PMID- 20286442 TI - Intensities of gamma rays, studied by means of their Compton secondaries. PMID- 20286443 TI - Conservatism in orthodontic procedures and appliances. PMID- 20286444 TI - The advisability of extraction as a therapeutic aid in orthodontics. PMID- 20286445 TI - The advisability of extraction as a therapeutic aid in orthodontics; affirmative. PMID- 20286446 TI - The advisability of extraction as a therapeutic aid in orthodontics; negative. PMID- 20286447 TI - The advisability of extraction as a therapeutic aid in orthodontics; negative. PMID- 20286448 TI - Extraction of teeth in orthodontics. PMID- 20286449 TI - Some limitations in orthodontic treatment. PMID- 20286450 TI - Heredity and the orthodontist; a study in confusion. PMID- 20286451 TI - The reduction of oral Lactobacillus acidophilus counts by the periodic restriction of carbohydrate. PMID- 20286452 TI - Recent advances in bacterial chemotherapy. PMID- 20286453 TI - Recent advances in bacterial chemotherapy; the antibiotics. PMID- 20286454 TI - Allergic dermatoses of importance to the dentist. PMID- 20286455 TI - The clinical diagnosis of dermatological lesions of the face and oral cavity. PMID- 20286456 TI - Dental education and practice in England and France. PMID- 20286457 TI - Fundamental principles associated with the retention of partial dentures. PMID- 20286458 TI - Fundamental principles associated with the retention of partial dentures. PMID- 20286459 TI - Preservation of the primary teeth. PMID- 20286460 TI - The intra-oral skin graft as an aid to denture construction. PMID- 20286461 TI - The use of penicillin and the sulfonamide drugs in dentistry. PMID- 20286462 TI - The use of penicillin lozenges in the treatment of Vincent's infection and other acute gingival inflammations. PMID- 20286463 TI - THE role of fluorine in dental caries; topical application of fluorides. PMID- 20286464 TI - Local anesthetic drugs. PMID- 20286465 TI - Cleft palate, a surgical and an orthodontic problem. PMID- 20286467 TI - Interception of malocclusion. PMID- 20286466 TI - The dentist and his heart. PMID- 20286468 TI - [Not Available]. PMID- 20286469 TI - Correction of traumatic occlusion is important subject in dentistry. PMID- 20286470 TI - Penicillin lozenges in the treatment of Vincent's stomatitis. PMID- 20286471 TI - Close bite; prevention and treatment. PMID- 20286472 TI - The treatment of fractured and displaced primary (deciduous) anterior teeth. PMID- 20286473 TI - The eosinophilic granulomas of the skin. PMID- 20286474 TI - Eosinophilic granuloma; theoretic and practical considerations based on the study of a case. PMID- 20286475 TI - Eosinophilic granuloma of the skin; its relation to erythema elevatum diutinum and eosinophilic granuloma of the bone; report of a case. PMID- 20286476 TI - Granulomatous Hodgkins' disease of the skin with extreme eosinophilia (eosinophilic granuloma of the skin?). PMID- 20286477 TI - Treatment of various types of cutaneous tuberculosis with promizole and streptomycin; a preliminary report. PMID- 20286478 TI - Elephantiasis neuromatosa; a manifestation of von Recklinghausen's disease. PMID- 20286479 TI - Dyskeratosis congenita with pigmentation, dystrophia unguium and leukoplakia oris; patient with evidence suggestive of Addison's disease. PMID- 20286480 TI - Primary lichen amyloidosis; report of necropsy. PMID- 20286481 TI - Hyperkeratosis of the palms and soles due to the ingestion of quinacrine hydrochloride. PMID- 20286482 TI - Pseudomonas aeruginosa infection of the ear treated with streptomycin. PMID- 20286484 TI - A case for diagnosis (ichthyosis hystrix? psoriasis?). PMID- 20286483 TI - Dermatitis from glass fabrics. PMID- 20286485 TI - Nevus pigmentosus. PMID- 20286486 TI - A case for diagnosis (lupus erythematosus? pemphigus?). PMID- 20286487 TI - Mycosis fungoides. PMID- 20286488 TI - Postarsphenamine vitiligo. PMID- 20286489 TI - Exudative discoid and lichenoid chronic dermatosis. PMID- 20286490 TI - Lupoid sycosis. PMID- 20286491 TI - A case for diagnosis (mycosis fungoides? arsenical dermatitis?). PMID- 20286492 TI - Contact dermatitis of the hands. PMID- 20286493 TI - [Not Available]. PMID- 20286494 TI - Parapsoriasis. PMID- 20286495 TI - [Not Available]. PMID- 20286496 TI - Urticaria pig mentosa (nodular type). PMID- 20286497 TI - Cutaneous horn. PMID- 20286498 TI - Acne conglobata. PMID- 20286499 TI - Pseudoxanthoma elasticum. PMID- 20286500 TI - Reticuloendotheliosis (mycosis fungoides?). PMID- 20286501 TI - Superficial epithelioma of bowenoid type. PMID- 20286502 TI - Pinta. PMID- 20286504 TI - Acanthosis nigricans. PMID- 20286503 TI - Papulopustular verrucous sporotrichosis simulating blastomycosis. PMID- 20286505 TI - A case for diagnosis (lymphoblastoma?). PMID- 20286506 TI - Psoriasis; arsenical pigmentation and keratoses; squamous cell epithelioma of the finger with metastasis to the axillary lymph nodes. PMID- 20286507 TI - Linchen planus with involvement of the palms. PMID- 20286508 TI - Larva migrans. PMID- 20286509 TI - Dermatosis, progressive pigmentary. PMID- 20286510 TI - A case for diagnosis (epidermolysis bullosa?). PMID- 20286511 TI - Actinomycosis. PMID- 20286512 TI - Annular, macular syphilid. PMID- 20286513 TI - Ulcers; acute pyogenic? factitial? anaerobic? PMID- 20286514 TI - Malignant melanoma. PMID- 20286515 TI - A case for diagnosis (lupus vulgaris?). PMID- 20286516 TI - Iodide dermatitis. PMID- 20286517 TI - Evipan used in the investigation of some chronic dermatoses. PMID- 20286518 TI - A case of multiple cutaneous horns in a young girl. PMID- 20286519 TI - Cutaneous Neukaemic deposits supervening on herpes zoster in a case of chronic lymphatic leukaemia. PMID- 20286520 TI - Secondary syphilis, sickling, malaria, sulphonamide and Herxheimer reactions in an African soldier. PMID- 20286521 TI - Case for diagnosis; lichen planus hypertrophicus? PMID- 20286522 TI - Haemorrhagic telangiectasia of Rendu-Osler-Weber. PMID- 20286523 TI - Case for diagnosis; lichen sclerosus? PMID- 20286524 TI - Lichen nitidus. PMID- 20286525 TI - Effect of calciferol on lupus vulgaris (two cases), lupus pernio and Boeck's sarcoid. PMID- 20286526 TI - Sarcoidosis treated with calciferol. PMID- 20286527 TI - Case for diagnosis; reticulosis? circumscribed myxoedema? PMID- 20286528 TI - Miliary lymphocytoma. PMID- 20286529 TI - Poison oak dermatitis; studies on hematologic, urinary and temperature changes. PMID- 20286530 TI - The nature of halogen sensitivity in dermatitis herpetiformis and pemphigus; a preliminary report. PMID- 20286531 TI - Modifications of the Goldman technique for contact testing of the buccal mucosa. PMID- 20286532 TI - Antipruritic qualities of papaverine hydrochloride. PMID- 20286533 TI - Steatocystoma multiplex; an analysis of their contents. PMID- 20286534 TI - Pyribenzamine in experimental nonallergic and allergic dermatitis. PMID- 20286535 TI - The spontaneous cure of tinea capitis in puberty. PMID- 20286536 TI - The cicatricial alopecias; an historical and clinical review and an histologic investigation. PMID- 20286537 TI - A simple and economical method of Rh typing. PMID- 20286538 TI - The use of magnesium sulphate in saline for the Kolmer Wassermann tests. PMID- 20286539 TI - Brucellosis. PMID- 20286540 TI - A case report of poliomyelitis (bulbar type). PMID- 20286541 TI - Tuberculous meningitis; a presentation of 3 cases. PMID- 20286542 TI - Eardrum and macro-cinematography in kodachrome. PMID- 20286543 TI - A new improved instrument for color photography; its use in the associated medical sciences. PMID- 20286544 TI - Medical photography in the Army. PMID- 20286545 TI - Amplifying lenses for biological photomicrography. PMID- 20286546 TI - Blackened shields for clear lamps in medical photography. PMID- 20286547 TI - Medical photographic records. PMID- 20286548 TI - An endoscopic color camera for otolaryngology and broncho-esophagology. PMID- 20286549 TI - Plastic embedded specimens as teaching aids. PMID- 20286550 TI - The use of unsaturated polyester resins for embedding biological material. PMID- 20286551 TI - Evisceration of frozen, defrosted, dressed poultry. PMID- 20286552 TI - Influence of mineral levels upon carotene and ascorbic acid contents of Swiss chard grown in the greenhouse. PMID- 20286553 TI - Relation of histological characteristics to texture in seed coats of peas. PMID- 20286554 TI - A note on use of Schultz and Olson lethal-rate paper for calculation of thermal processes for food products in tin containers. PMID- 20286555 TI - Effect of French dressings, vinegars, and acetic acid on rate of loss of vitamin C in raw cabbage. PMID- 20286556 TI - Nutritive value of fish from Michigan waters; thiamin of lake herring, carp, common sucker, burbot, and smelt. PMID- 20286557 TI - Direct colorimetric method and its application to determination of enzymatic discoloration in white potatoes. PMID- 20286558 TI - Bacteriological investigation on spoilage of winter herring during storage. PMID- 20286559 TI - Niacin, riboflavin, and thiamin studies on dehydrated pork loaves. PMID- 20286560 TI - The World Health Organization and global nutrition. PMID- 20286561 TI - Principles of nutritional rehabilitation. PMID- 20286562 TI - Nutritional policies in Great Britain, 1939-46. PMID- 20286563 TI - Nutritional appraisal and demonstration program of the U.S. Public Health Service. PMID- 20286565 TI - Further studies on nutritional improvement of cereal flours and cereal grains with yeast. PMID- 20286564 TI - The dietary management of spontaneous hypoglycemia. PMID- 20286566 TI - Palatability and ascorbic acid retention of rutabaga, peas, and cabbage after holding on the steam table. PMID- 20286567 TI - Pteroylglutamic acid in nutrition. PMID- 20286568 TI - A preliminary report of the folic acid content of certain foods. PMID- 20286569 TI - The influence of some recent studies on the interpretation of the findings of nutrition surveys. PMID- 20286570 TI - Metabolism of women during the reproductive cycle; the utilization of vitamin A during lactation. PMID- 20286571 TI - Food value of hormone-treated tomatoes. PMID- 20286572 TI - Effect of quantity preparation on the ascorbic acid content of cabbage salad. PMID- 20286573 TI - The nutritive value of canned foods; further studies on carotene, ascorbic acid, and thiamine. PMID- 20286574 TI - The relationship of nicotinic acid, tryptophane and protein in the nutrition of the pig. PMID- 20286575 TI - Riboflavin deficiency in the dairy calf. PMID- 20286576 TI - The formation of capillaries and other tissue changes in the cornea of the methionine-deficient rat. PMID- 20286577 TI - Work performance, respiratory exchange, and certain blood constituents after isocaloric meals of low and high carbohydrate content. PMID- 20286578 TI - Improving the nutritive value of flour; the effect of supplementing enriched flour with other B-complex vitamins. PMID- 20286579 TI - Amino acids required to supplement linseed protein for chick growth. PMID- 20286580 TI - An inborn characteristic determining the response of chickens to a diet free of animal protein. PMID- 20286581 TI - Surface area and metabolism of growing guinea pigs. PMID- 20286582 TI - On the growth-promoting factor for rats present in summer butter. PMID- 20286584 TI - The geography of Salmonella. PMID- 20286583 TI - The growth promoting action of vaccenic acid. PMID- 20286585 TI - A clinical consideration of the malfunctioning noncalculus gall bladder. PMID- 20286586 TI - An attempt to prevent histamine-induced ulcers in guinea pigs with benadryl (beta dimethylamino-ethylbenzhydryl ether hydrochloride). PMID- 20286587 TI - Some effects of high lipid diets on intestinal elimination; saturated fatty acids. PMID- 20286588 TI - The formation of concretions of aluminum salts of fatty acids after the use of aluminum hydroxide. PMID- 20286589 TI - Management of constipation with a refined psyllium combined with dextrose. PMID- 20286590 TI - The cause and pathogenetic mechanism of hypertrophic cirrhosis of the liver of the Hanot type. PMID- 20286591 TI - Organotherapy in ulcerative colitis, a new and interesting therapy. PMID- 20286592 TI - [Not Available]. PMID- 20286593 TI - [Not Available]. PMID- 20286594 TI - [Not Available]. PMID- 20286595 TI - [Not Available]. PMID- 20286596 TI - [Not Available]. PMID- 20286597 TI - [Not Available]. PMID- 20286598 TI - [Not Available]. PMID- 20286599 TI - [Not Available]. PMID- 20286600 TI - [Not Available]. PMID- 20286601 TI - [Not Available]. PMID- 20286602 TI - [Not Available]. PMID- 20286603 TI - Variations in regulation of energy exchange associated with estrus, diestrus and pseudopregnancy in rats. PMID- 20286604 TI - The early reduction in uterine response to alpha estradiol in the partially hepatectomized rat, and the subsequent enhancement during active liver regeneration. PMID- 20286605 TI - The rate of turnover of protein-bound iodine in the plasma of the dog as measured with radioactive iodine. PMID- 20286606 TI - The effect of hyperglycemia on insulin secretion as determined with the isolated rat pancreas in a perfusion apparatus. PMID- 20286607 TI - Suppression of insulin secretion by the growth hormone of the anterior pituitary as determined with the isolated rat pancreas in a perfusion apparatus. PMID- 20286608 TI - The essential lesion in experimental diabetes insipidus. PMID- 20286609 TI - Effect of thiouracil on oxidation of paraphenylendiamine by various tissues. PMID- 20286610 TI - Increased pituitary and adrenal weight produced by estrone in intact and castrated normal and runt rats. PMID- 20286611 TI - A study of evolutionary chromosome changes in Sciara (Diptera); chromosome C in the salivary gland cells of Sciara ocellaris and Sclara reynoldsi. PMID- 20286612 TI - On the synthesis of gene-products in equimolecular quantities. PMID- 20286613 TI - Breeding, rearing and care of the South African clawed frog (Xenopus laevis). PMID- 20286614 TI - The induction of germinal mutations by chemical means. PMID- 20286615 TI - Effectiveness of intraspecific and interspecific matings in Drosophila pseudoobscura and Drosophila persimilis. PMID- 20286616 TI - Tumor formation in relation to the origin of viruses. PMID- 20286617 TI - Spontaneous mutation rate in Drosophila. PMID- 20286618 TI - Galton on eugenics as science and practice. PMID- 20286619 TI - Danish experiences in negative eugenics, 1929-45. PMID- 20286620 TI - Studies on impaired fertility in the male. PMID- 20286622 TI - A cancer control project in a planned parenthood center. PMID- 20286621 TI - Experiences with artificial insemination. PMID- 20286623 TI - Population control and world health. PMID- 20286624 TI - NATIONAL health program and planned parenthood; a Catholic view. PMID- 20286625 TI - Six types of neurotic reaction to a husband's request for a divorce. PMID- 20286626 TI - Factors underlying family instability. PMID- 20286627 TI - Meeting the family's medical costs. PMID- 20286628 TI - The application of our knowledge of the Rh factor. PMID- 20286629 TI - Masculinizing tumor of the ovary of the adrenal type. PMID- 20286630 TI - Radium and roentgen therapy in the treatment of menopausal uterine bleeding. PMID- 20286631 TI - Sodium pentothal anesthesia in major obstetric and gynecologic surgery; preliminary report of 300 cases. PMID- 20286632 TI - Leucoplakia vulvae; its etiology and results of treatment with vitamin A; preliminary report. PMID- 20286633 TI - A spiral artery in the ovary of the rabbit. PMID- 20286634 TI - An evaluation of presacral neurectomy in the treatment of dysmenorrhea. PMID- 20286635 TI - A study of the bacterial flora of the normal and pathologic vagina and uterus. PMID- 20286636 TI - The treatment of mycotic vulvovaginitis with propionate vaginal jelly. PMID- 20286637 TI - Ovarian adenoacanthoma associated with endometriosis of the ovary. PMID- 20286638 TI - Recognition of midpelvic contraction. PMID- 20286639 TI - Control of menstrual disturbances and hypo-ovarian sterility; nine years of experience with equine gonadotropin. PMID- 20286641 TI - Surgery in the uterine fibroid, a plea for myomectomy. PMID- 20286640 TI - Mixed synthetic estrogens; their use in the menopause (dimethoxy stilbestrol and diethylstilbestrol). PMID- 20286642 TI - Third stage of labor; measurement of blood loss; intravenous ergotrate. PMID- 20286643 TI - Relation of the fetus and placenta to the decline of hypertension in pregnant rats. PMID- 20286644 TI - Effect of pregneninolone on the menstrual cycle of adolescent girls with oligomenorrhea or amenorrhea. PMID- 20286645 TI - Epidemic diarrhea in the newborn; the relation between breast and bottle feeding and the early development of the proper intestinal flora. PMID- 20286646 TI - Pelvic examination for nurses. PMID- 20286647 TI - An analysis of 212 consecutive cases of ectopic pregnancy. PMID- 20286648 TI - Parenteral vitamin K therapy during the antepartum period and its effects on the infants prothrombin levels. PMID- 20286649 TI - Maternal pulmonary embolism by contents of the amniotic fluid. PMID- 20286650 TI - Oil embolism following hysterosalpingography. PMID- 20286651 TI - Estrogenic tolerance in pregnant women. PMID- 20286652 TI - An evaluation of the pregnancy test based on ovarian hyperemia in the immature rat. PMID- 20286653 TI - Pregnancy complicated by double uterus, cervix, and vagina. PMID- 20286654 TI - Bacteriology of vagina in total hysterectomy. PMID- 20286655 TI - Placenta accreta found at cesarean section for placenta previa, with preservation of the uterus. PMID- 20286656 TI - Early form of secondary abdominal pregnancy. PMID- 20286657 TI - Meigs' syndrome in theca-cell tumor of the ovary. PMID- 20286658 TI - Pregnancy and sickle-cell anemia. PMID- 20286659 TI - Fibroadenoma of supernumerary mammary gland tissue in vulva. PMID- 20286660 TI - Dichorial unilateral tubal twins. PMID- 20286661 TI - Bilateral harelip and unilateral harelip with cleft palate in fraternal twins. PMID- 20286662 TI - Combined extrauterine and intrauterine pregnancy. PMID- 20286663 TI - Postmortem cesarean section. PMID- 20286664 TI - [Not Available]. PMID- 20286665 TI - [Not Available]. PMID- 20286666 TI - [Not Available]. PMID- 20286667 TI - [Not Available]. PMID- 20286668 TI - [Not Available]. PMID- 20286669 TI - [Not Available]. PMID- 20286670 TI - [Not Available]. PMID- 20286671 TI - [Not Available]. PMID- 20286672 TI - [Not Available]. PMID- 20286673 TI - [Not Available]. PMID- 20286674 TI - [Not Available]. PMID- 20286675 TI - [Not Available]. PMID- 20286676 TI - [Not Available]. PMID- 20286677 TI - [Not Available]. PMID- 20286678 TI - [Not Available]. PMID- 20286679 TI - [Not Available]. PMID- 20286680 TI - [Not Available]. PMID- 20286681 TI - [Not Available]. PMID- 20286682 TI - [Not Available]. PMID- 20286683 TI - [Not Available]. PMID- 20286684 TI - [Not Available]. PMID- 20286685 TI - [Not Available]. PMID- 20286686 TI - [Not Available]. PMID- 20286687 TI - [Not Available]. PMID- 20286688 TI - [Not Available]. PMID- 20286689 TI - [Not Available]. PMID- 20286690 TI - [Not Available]. PMID- 20286692 TI - [Not Available]. PMID- 20286691 TI - [Not Available]. PMID- 20286693 TI - [Not Available]. PMID- 20286694 TI - [Not Available]. PMID- 20286695 TI - [Not Available]. PMID- 20286696 TI - [Not Available]. PMID- 20286699 TI - FORTUNATE accidents in medical history. PMID- 20286700 TI - John of St Amand on the magnet. PMID- 20286701 TI - [Not Available]. PMID- 20286703 TI - An American historian looks at science and technology. PMID- 20286702 TI - On Faraday's terminology in electrolysis. PMID- 20286704 TI - The age at which scientists do their best work. PMID- 20286705 TI - Sixty-ninth critical bibliography of the history and philosophy of science and of the history of civilization (to December 1945). PMID- 20286706 TI - BCG vaccination in Saskatchewan hospitals and sanatoria. PMID- 20286707 TI - Narcotic control in hospitals. PMID- 20286708 TI - Hospital requirements as dictated by modern trends. PMID- 20286709 TI - SUPPRESSION of radiation from short-wave diathermy machines. PMID- 20286710 TI - Microfilming in Canadian hospitals. PMID- 20286711 TI - Getting along with the public. PMID- 20286712 TI - News of Blue Cross plan for hospital care. PMID- 20286713 TI - Some aspects of hospital planning. PMID- 20286714 TI - News of Blue Cross plan for hospital care. PMID- 20286715 TI - Integration of hospital service. PMID- 20286716 TI - The functions of a general hospital. PMID- 20286717 TI - The report of the Commission on Hospital Care. PMID- 20286718 TI - The role of the Central Service for the chronically ill. PMID- 20286719 TI - Resume of the problems of chronic illness. PMID- 20286720 TI - Health education and community agencies in prevention and control of particular diseases. PMID- 20286721 TI - How does ambulance service work? how much does it cost. PMID- 20286722 TI - Individual health and social security; some logical comparisons; the sorry subject of government aid and what has happened to security. PMID- 20286723 TI - Education of the hospital trustee. PMID- 20286724 TI - Code of ethics for Catholic hospitals. PMID- 20286726 TI - Commission on hospital care. PMID- 20286725 TI - National Mental Health Law; Public Law 487. PMID- 20286727 TI - The Hospital Survey and Construction Act (Public Law 725). PMID- 20286728 TI - Personnel policy and practice. PMID- 20286729 TI - Social security; Old Age and Survivors Insurance and the tax exempt status of a Catholic hospital. PMID- 20286730 TI - The purchase of hospital care by agencies of the Federal Government in the Catholic hospitals. PMID- 20286731 TI - Ethics for modern nurses. PMID- 20286732 TI - The Catholic hospitals among the hospitals of the United States. PMID- 20286733 TI - Appointment to internships. PMID- 20286734 TI - Professional intraining program for the nursing sister. PMID- 20286736 TI - WHAT about the nursing shortage? PMID- 20286735 TI - Oxygen supply as convenient as water at St. Francis Hospital, Peoria. PMID- 20286737 TI - Progress in antibiotic therapy. PMID- 20286738 TI - Choline; an effective treatment in cirrhosis. PMID- 20286739 TI - Centralisation in the new hospital service; its probable extent in administration. PMID- 20286740 TI - Hospital planning; plan examples from abroad. PMID- 20286741 TI - Personnel management in hospitals is needed now. PMID- 20286742 TI - Hospital planning; ward units. PMID- 20286743 TI - Guide to the National Health Service Act, 1946. PMID- 20286744 TI - The Soder Hospital, Stockholm; its planning and shaping; studies of principles. PMID- 20286745 TI - Aluminium and aluminium alloys; their application for hospital use. PMID- 20286746 TI - Sanatorium design; planning of a 320 bed unit for pulmonary tuberculosis. PMID- 20286747 TI - Pathology Institute proves this point; cooperation among hospitals in essential to modern medicine. PMID- 20286748 TI - The mental health of childhood requires active, continuous cooperation between pediatrician and psychiatrist. PMID- 20286749 TI - Blue Cross in the public health; report of the U.S.P.H.S. survey. PMID- 20286750 TI - Management and financing of municipal hospitals. PMID- 20286751 TI - The doctor looks at nursing service. PMID- 20286752 TI - The emergency room; another hazard for the accident victim. PMID- 20286753 TI - FUNCTIONAL basis of hospital planning. PMID- 20286754 TI - Helping Greece take the road to health. PMID- 20286756 TI - Admitting communicable cases. PMID- 20286755 TI - Psychiatry; modern quarters for the mentally ill. PMID- 20286757 TI - The economics of anesthesiology service. PMID- 20286758 TI - On scientific writing. PMID- 20286759 TI - Attitudes of progressive trade-union leaders. PMID- 20286760 TI - The nature of the ethnic group. PMID- 20286761 TI - Race prejudice and Negro-white relations in the Army. PMID- 20286762 TI - Officer-enlisted men's relationships. PMID- 20286764 TI - Selection of compatible flying partners. PMID- 20286763 TI - The chaplain and mental hygiene. PMID- 20286765 TI - Final note on a case of extreme isolation. PMID- 20286766 TI - Operational definitions in sociology. PMID- 20286767 TI - Quinone vapors and their harmful effects; corneal and conjunctival injury. PMID- 20286768 TI - Quinone vapors and their harmful effects; plant exposures associated with eye injuries. PMID- 20286769 TI - Toxicity of 2,4 dichlorophenoxyacetic acid for experimental animals. PMID- 20286770 TI - A study of the hazards of exposure to metallic fumes and dust in brass foundries. PMID- 20286771 TI - A study of pneumonia in shipyard workers, with special reference to welders. PMID- 20286772 TI - The acute and chronic toxicity of methyl chloride; symptomatology of animals poisoned by methyl chloride. PMID- 20286773 TI - Microscopic detection of cadmium oxide particles in lung tissue. PMID- 20286774 TI - Doudenal ulcer following exposure to carbon tetrachloride; report of two cases. PMID- 20286775 TI - A rapid method for the determination of chromic acid mist in air. PMID- 20286776 TI - Loose versus close-fitting clothing for work in tropical heat. PMID- 20286777 TI - Sociological factors in the alcohol problem. PMID- 20286778 TI - Effects chiefly mental. PMID- 20286779 TI - Lesser degrees of intoxication. PMID- 20286781 TI - PRE-COURT medical examination proposed. PMID- 20286780 TI - Alcoholics crowd the court. PMID- 20286782 TI - Signs of vertical keratinization in a pathological mucified pavement-like epithelium. PMID- 20286783 TI - [Not Available]. PMID- 20286784 TI - [Not Available]. PMID- 20286785 TI - [Not Available]. PMID- 20286786 TI - [Not Available]. PMID- 20286787 TI - Influence of interruption of renal innervation on the action of pharmaca in diuresis. PMID- 20286788 TI - [Not Available]. PMID- 20286789 TI - [Not Available]. PMID- 20286790 TI - On the influence of bread baked with paraffine-oil, mineral paraffine or synthetic wax, on the growth of rats and chickens. PMID- 20286791 TI - [Not Available]. PMID- 20286792 TI - [Not Available]. PMID- 20286793 TI - [Not Available]. PMID- 20286794 TI - The action of cicutoxin. PMID- 20286795 TI - The aneurin-pyrophosphate content of human organs. PMID- 20286796 TI - The determination and excretion of lactoflavin. PMID- 20286797 TI - [Not Available]. PMID- 20286798 TI - [Not Available]. PMID- 20286799 TI - X-ray therapy in non-malignant diseases. PMID- 20286800 TI - A graphic examination method of the spinal column. PMID- 20286801 TI - Acute myocarditis as a sequel to infectious mononucleosis. PMID- 20286802 TI - Rh incompatibility and foetal prognosis. PMID- 20286803 TI - Asphyxia neonatorum. PMID- 20286804 TI - Psychological methods of obtaining medical information. PMID- 20286805 TI - Penicillin therapy of early syphilis. PMID- 20286806 TI - The treatment of recurrent shoulder dislocation with autohaemo-injections. PMID- 20286807 TI - Mumps with an oedema of the anterior wall of the whole body. PMID- 20286808 TI - Klippel-Feil malformation associated with syringomyelia. PMID- 20286810 TI - Sustained local anaesthesia. PMID- 20286809 TI - Sympathetic surgery; a review of two hundred and twenty five operations. PMID- 20286811 TI - A direct titrimetric method for the determination of albumin in serum and plasma. PMID- 20286812 TI - Phlegmasia alba dolens in early puerperium without fever or permanent tachycardia. PMID- 20286813 TI - Medical and vital statistics. PMID- 20286814 TI - Mixed thyroidism. PMID- 20286815 TI - Granuloma venereum in Palestine. PMID- 20286816 TI - Right bundle branch block (Wilson) following measles. PMID- 20286817 TI - Tropical and phagedenic ulcer and desert sore; a review. PMID- 20286818 TI - Streptomycin treatment of urinary tract infections, with special reference to the use of alkali. PMID- 20286819 TI - Dienestrol; another synthetic estrogen of clinical value. PMID- 20286820 TI - Bacillus pyocyaneus infections; a review, report of cases and discussion of newer therapy including streptomycin. PMID- 20286821 TI - Rheumatic heart disease in the adult. PMID- 20286822 TI - Treatment of acute rheumatic fever and acute rheumatic heart disease. PMID- 20286823 TI - The dose of a drug. PMID- 20286824 TI - Blood dyscrasia with cardiac complications. PMID- 20286825 TI - Permanent heart block following German measles. PMID- 20286826 TI - The dangerous carrier of hemolytic streptococci. PMID- 20286827 TI - Diagnosis of surgical lesions of the thorax. PMID- 20286828 TI - Streptomycin in clinical practice; a review and case reports. PMID- 20286829 TI - Urologic complications of pregnancy and labor. PMID- 20286830 TI - The problem of hypertension. PMID- 20286831 TI - Salient features of the diagnosis of chronic rheumatic valvular heart disease: illustrative cases. PMID- 20286832 TI - Anesthesia in geriatric practice. PMID- 20286833 TI - An unusual case of endemic typhus fever. PMID- 20286834 TI - Vitamin deficiency diseases in infants. PMID- 20286835 TI - The treatment of peptic ulcer with special reference to vagotomy. PMID- 20286836 TI - Significance and management of the obstructive factor in cardiac asthma and cardiac dyspnea. PMID- 20286837 TI - The heart in thyroid disease. PMID- 20286838 TI - Anuria. PMID- 20286839 TI - Spontaneous pleural effusions. PMID- 20286840 TI - Endemic typhus fever. PMID- 20286841 TI - The diagnosis of cerebral aneurysms. PMID- 20286842 TI - Neurodermatitis. PMID- 20286843 TI - Psychosomatic diagnosis. PMID- 20286844 TI - Penicillin in cincophen-induced agranulocytosis. PMID- 20286845 TI - The treatment of acute rheumatic fever. PMID- 20286846 TI - Interviewing technics. PMID- 20286848 TI - The initial care of casualties. PMID- 20286847 TI - Folic acid in the treatment of macrocytic anemias. PMID- 20286849 TI - The symptomatic treatment of bronchial asthma in infancy and childhood. PMID- 20286850 TI - Neurologic manifestations in the pre-icteric phase of infectious hepatitis. PMID- 20286851 TI - Research and the general practitioner. PMID- 20286852 TI - The treatment of functional uterine hemorrhage. PMID- 20286853 TI - Rheumatic fever; preventive aspects. PMID- 20286854 TI - Proctologic considerations of interest to internists. PMID- 20286855 TI - What the physician should know about foreign bodies that have been swallowed. PMID- 20286856 TI - Tic douloureux; report of a case successfully treated with intravenous typhoid vaccine. PMID- 20286857 TI - The cardiac complications of meningoccoccus infection; pericarditis occurring in the course of sulfadiazine treated meningitis. PMID- 20286858 TI - Artificial insemination: its medicolegal implications; a symposium. PMID- 20286859 TI - Artificial insemination: its medicolegal implications; legal aspects. PMID- 20286860 TI - Diagnosis and treatment of cancer of the uterus. PMID- 20286861 TI - The differential diagnosis of aortic stenosis, pulmonary stenosis, patent ductus arteriosus and coarctation of the aorta. PMID- 20286862 TI - Peripheral vascular sclerosis. PMID- 20286863 TI - Management of vivax malaria in the veteran. PMID- 20286864 TI - Diagnosis and management of peripheral nerve injuries. PMID- 20286865 TI - Clinical physiology of infectious diseases of the liver. PMID- 20286866 TI - Atypical pneumonia with x-ray findings simulating tuberculosis. PMID- 20286867 TI - Maintaining nitrogen balance with amino acids; four adults maintained by acid hydrolyzed casein fortified with one per cent dl-tryptophane given orally. PMID- 20286868 TI - Prematurity from the viewpoint of the obstetrician. PMID- 20286869 TI - The role of vitamin deficiencies in neuropsychiatric diseases. PMID- 20286870 TI - Symposium on scientific tests in evidence. PMID- 20286871 TI - Chemical tests for alcoholic intoxication. PMID- 20286872 TI - Legal problems regarding blood grouping tests in paternity cases and scientific tests for alcoholic intoxication. PMID- 20286873 TI - Lymphogranuloma venereum. PMID- 20286874 TI - Abdominal auscultation. PMID- 20286875 TI - Hypertensive encephalopathy. PMID- 20286876 TI - Multiple myeloma. PMID- 20286877 TI - Erythema multiforme. PMID- 20286878 TI - Carcinoma of the prostate. PMID- 20286879 TI - The treatment of the migraines. PMID- 20286880 TI - Syphilis of the breast; chancre and gumma. PMID- 20286881 TI - Constitution of coumarins isolated from Ferula alliacea. PMID- 20286882 TI - Proteolytic system in the blood of tuberculosis and typhoid patients. PMID- 20286883 TI - Effect of alloxan on insulin. PMID- 20286884 TI - Comparative action of trypsin on amorphous insulin, crystalline-zn-insulin, protamine-zn-insulin and globin insulin. PMID- 20286885 TI - Observations on ascorbic acid; the effect of certain factors on ascorbic acid production during germination of seeds. PMID- 20286886 TI - A modified procedure for the estimation of nicotinic acid in biological materials. PMID- 20286887 TI - On the antibacterial activity of sulpha drugs against bacillary dysentery organisms. PMID- 20286888 TI - Chemotherapeutic study of pneumococcal infections. PMID- 20286889 TI - Studies on the nutritive value of soya milk; nutritive value of the protein. PMID- 20286890 TI - Studies on the nutritive value of soya milk; comparison of the vitamin B complex content of soya milk and cow's milk. PMID- 20286891 TI - Studies on the nutritive value of soya-bean milk; supplementing value of soya milk to a poor Indian diet. PMID- 20286892 TI - Studies on the nutritive value of soya milk; digestibility of soya milk; in vitro experiments. PMID- 20286893 TI - Improvements in the cyanogen bromide method for the determination of nicotinic acid in urine. PMID- 20286894 TI - Nutritional investigations on Bengal fish. PMID- 20286895 TI - Vitamin A reserve in human liver. PMID- 20286896 TI - Effect of temperature on the stability of cobravenom and cardiotoxin. PMID- 20286897 TI - Effect of methylene blue on the toxicity of cobra venom. PMID- 20286898 TI - Effect of ultra-violet rays on the stability of cobra-venom and cardiotoxin. PMID- 20286900 TI - Studies on choline-esterase. PMID- 20286899 TI - Effect of different adsorbents on the toxicity of cobra-venom. PMID- 20286901 TI - Medicine in the European Theater of Operations. PMID- 20286902 TI - Scrub typhus in Dutch New Guinea. PMID- 20286903 TI - The treatment of acute bacterial endocarditis with penicillin. PMID- 20286904 TI - Cardiac arrhythmias complicating total pneumonectomy. PMID- 20286905 TI - Rheumatoid spondylitis: a study of 1,035 cases. PMID- 20286906 TI - Trichinosis: report of an epidemic. PMID- 20286908 TI - Stevens-Johnson syndrome, a variation of erythema multiforme exsudativum (Hebra) a report of two cases. PMID- 20286907 TI - Pleuropulmonary tularemia: observations on 12 cases treated with streptomycin. PMID- 20286909 TI - Coarctation of the aorta. PMID- 20286910 TI - Onchocerciasis; case report. PMID- 20286911 TI - Anaphylaxis to the injection of nicotinic acid (niacin); successful treatment with epinephrine. PMID- 20286912 TI - A case of fulminating meningococcemia exhibiting the Waterhouse-Friderichsen syndrome and demonstrating the value of cortical extract administration. PMID- 20286913 TI - [Not Available]. PMID- 20286914 TI - [Not Available]. PMID- 20286915 TI - [Not Available]. PMID- 20286917 TI - The acute abdomen. PMID- 20286916 TI - [Not Available]. PMID- 20286918 TI - Craniocerebral trauma. PMID- 20286919 TI - Bilateral hypoplasia of kidneys with report of a case. PMID- 20286920 TI - The effect of altering the ionic content of sera in vivo on syphilis serology. PMID- 20286921 TI - RADIOACTIVE phosphorus as a therapeutic agent. PMID- 20286922 TI - The surgical relief of severe angina pectoris. PMID- 20286923 TI - Practical principles of active immunization. PMID- 20286924 TI - New clinical syndrome; delayed chemical pneumonitis occurring in workers exposed to beryllium compounds. PMID- 20286925 TI - Hepatic function with respect to bromsulphalein removal. PMID- 20286926 TI - Epidemic hepatitis. PMID- 20286927 TI - Benign paroxysmal peritonitis; a case report. PMID- 20286928 TI - Muscular atrophies and dystrophies. PMID- 20286929 TI - Congenital alveolar dysplasia of the lungs. PMID- 20286931 TI - Highlights of ophthalmology. PMID- 20286930 TI - Tuberculosis control program in San Francisco. PMID- 20286932 TI - Highlights of ophthalmology. PMID- 20286933 TI - Vagotomy. PMID- 20286934 TI - History of Vancouver Medical Association. PMID- 20286935 TI - Modern trends in obstetrics. PMID- 20286936 TI - Clinical differentiation in the syndrome called atypical pneumonia. PMID- 20286937 TI - The use and limitations of hearing aids. PMID- 20286938 TI - Chronic empyema. PMID- 20286939 TI - Splenosis. PMID- 20286940 TI - New factors in the etiology of obliterative arterial disease. PMID- 20286941 TI - The surgery of heart disease. PMID- 20286942 TI - Surgical management of gangrenous bowel in infancy. PMID- 20286943 TI - Cerebral air embolism following artificial pneumothorax; treatment with prolonged inhalation of oxygen. PMID- 20286944 TI - The management of asthma. PMID- 20286945 TI - Folic acid in the treatment of pernicious anaemia. PMID- 20286946 TI - Personality changes associated with surgical and radiation castration. PMID- 20286947 TI - Auricular flutter (the results of therapy in a general hospital over a ten-year period.). PMID- 20286948 TI - Myopia. PMID- 20286949 TI - The etiology and treatment of hyperemesis gravidarum. PMID- 20286950 TI - Psychomotor epilepsy. PMID- 20286951 TI - Brucellosis. PMID- 20286952 TI - The treatment of motion sickness. PMID- 20286953 TI - Sarcoma of the prostate. PMID- 20286954 TI - Air embolism during labour. PMID- 20286955 TI - A case of pentosuria. PMID- 20286956 TI - A case of actinomycosis treated with streptomycin. PMID- 20286957 TI - The folic acid story. PMID- 20286958 TI - Tetraethyl ammonium chloride; a new drug useful in the field of peripheral vascular diseases. PMID- 20286959 TI - A blood sugar test. PMID- 20286960 TI - Linnaeus, botanist and physician. PMID- 20286961 TI - Anergy in infants' skin to diphtheria toxin. PMID- 20286962 TI - Anatomical changes in the liver after trauma. PMID- 20286963 TI - Effects of venesection in low output heart failure. PMID- 20286964 TI - Observations on the headache accompanying fever. PMID- 20286965 TI - Observations on the mechanism of pain in ulcer of the stomach and duodenum. PMID- 20286966 TI - Observations on the mechanism of pain in ulcer of the stomach and duodenum; the location of the pain nerve endings. PMID- 20286967 TI - The use of a portal anastomotic vein for absorption studies in man. PMID- 20286968 TI - Ringworm of the scalp. PMID- 20286969 TI - The diagnosis of intraocular tumors; a demonstration of kodachrome slides. PMID- 20286970 TI - Hyaluronidase. PMID- 20286971 TI - A skin test to measure susceptibility to whooping cough; preliminary report. PMID- 20286972 TI - Physiologic and antibiotic (penicillin) therapy in chronic hypertrophic pulmonary emphysema. PMID- 20286973 TI - Treatment of thoracic empyema with sodium tetradecyl sulfate 1: 500 in azochloramid 1:3300. PMID- 20286974 TI - Treatment of tension cavities with pneumothorax. PMID- 20286975 TI - Pneumoperitoneum with diaphragmatic paralysis in the treatment of pulmonary tuberculosis. PMID- 20286977 TI - Molluscum contagiosum. PMID- 20286976 TI - Report on streptomycin in tuberculosis. PMID- 20286978 TI - Problems in arterial surgery. PMID- 20286979 TI - High blood pressure. PMID- 20286980 TI - High blood pressure. PMID- 20286981 TI - Disseminated tuberculosis. PMID- 20286982 TI - Before and after Laennec. PMID- 20286983 TI - The laboratory diagnosis of influenza; a summary of current methods. PMID- 20286984 TI - A case of calcinosis universalis. PMID- 20286985 TI - The influence of the distant electrode on the electrogram and electrocardiogram observations during pneumonolysis. PMID- 20286986 TI - An evaluation of Einthoven's law of the values in the three leads. PMID- 20286987 TI - Mammary glands of the rat during growth and senescence. PMID- 20286988 TI - Observations on vessel and organ transplants. PMID- 20286989 TI - Colloid-chemical changes of serum albumin during adsorption and dehydration. PMID- 20286990 TI - Investigations on the potential fluctuations existing at the central terminal electrode. PMID- 20286991 TI - Indications and contra-indications of strophanthin (ouabain) treatment. PMID- 20286992 TI - Penicillin therapy in general practice; surgical aspects. PMID- 20286993 TI - Penicillin therapy; laboratory aspects. PMID- 20286994 TI - Observations on the operative treatment of two cases of irreducible intussusception. PMID- 20286995 TI - Survey of present methods of treatment of meningitis. PMID- 20286996 TI - Carcinoma of the hepatic ducts; a case report. PMID- 20286997 TI - Gastro-intestinal trichinosis as a surgical problem. PMID- 20286998 TI - A review of the meningitides at the Robert Packer Hospital. PMID- 20286999 TI - Acute, complete acromioclavicular dislocation. PMID- 20287000 TI - Meningioma of the spinal cord; a case report. PMID- 20287001 TI - Sarcoma of the kidney; a case report. PMID- 20287002 TI - Neuroblastoma of the thorax; a case report. PMID- 20287003 TI - Multiple primary malignant tumors. PMID- 20287004 TI - Chronic subdural hematoma in infancy; a clinical report. PMID- 20287005 TI - Primary malignancy of small intestine. PMID- 20287006 TI - Crossed renal ectopia; unfused type. PMID- 20287008 TI - Chlorophyll therapy; a review of 114 cases. PMID- 20287007 TI - Streptococcus fecalis septicemia; concluding report of a case. PMID- 20287009 TI - Carcinoma of the body of the pancreas; a case report. PMID- 20287010 TI - Vertigo. PMID- 20287011 TI - The importance of psychological factors in organic disease. PMID- 20287012 TI - A case of intra-arterial injection of pentothal sodium. PMID- 20287013 TI - The heraldry at Guy's Hospital. PMID- 20287014 TI - A case of belladonna poisoning. PMID- 20287015 TI - Morphological variation in the histiocytes of mice and men. PMID- 20287016 TI - The odontomes and other affections of the jaws; their pathology, diagnosis and treatment. PMID- 20287017 TI - Studies in lung abscess; Friedlander abscess of the lung. PMID- 20287018 TI - Diaphragmatic hernia following transthoracic gastrectomy. PMID- 20287019 TI - Vertigo and its associated diagnostic signs. PMID- 20287020 TI - Changing indications for cesarean section. PMID- 20287021 TI - A renal function test for office use. PMID- 20287022 TI - Advances in general surgery. PMID- 20287023 TI - Pneumothorax therapy in an overseas hospital. PMID- 20287024 TI - The comparative value of some methods of treatment in cases of tropical ulcer. PMID- 20287025 TI - Crude and refined liver extract in nutritional macrocytic anaemia. PMID- 20287027 TI - Basal metabolic studies in the Punjab. PMID- 20287026 TI - Study of liver diseases; correlation of clinical and liver function studies with liver biopsy. PMID- 20287028 TI - Myoepithelial tumours of the salivary glands; report of three cases. PMID- 20287029 TI - Achalasia cardia (cardiospasm). PMID- 20287030 TI - Amoebic granuloma (amoeboma) of the large intestine. PMID- 20287031 TI - Observations on yaws in Bastar State. PMID- 20287032 TI - Sodium antimony v. gluconate in the treatment of Indian kala-azar. PMID- 20287033 TI - Epidemiology of filariasis in certain parts of H.E.H. the Nizam's State. PMID- 20287034 TI - Plague-meningitis. PMID- 20287035 TI - Serological technique; determination of blood groups from stains. PMID- 20287036 TI - A case of leiomyoma cutis. PMID- 20287037 TI - Quinine. PMID- 20287038 TI - Incidence of infectious disease during the Puri car festival, 1946. PMID- 20287039 TI - Action of certain antimalarial drugs on plasma prothrombin level in normal and malarial subjects. PMID- 20287040 TI - Some problems in surgical treatment of gastro-duodenal ulcer and the value of partial gastrectomy. PMID- 20287041 TI - Weil's disease; leptospirosis icterohaemorrhagica treated with penicillin. PMID- 20287042 TI - Present trends in tuberculosis. PMID- 20287043 TI - Aspects of the tuberculosis problem in Eire. PMID- 20287044 TI - Is B.C.C. vaccination a practical proposition for Eire? PMID- 20287045 TI - The use of B.C.G. in Eire. PMID- 20287046 TI - Clinical research in Ireland. PMID- 20287047 TI - The production of avid diphtheria antitoxin. PMID- 20287048 TI - Observations on hysterectomy. PMID- 20287049 TI - The copper sulphate method in routine haematological examinations. PMID- 20287050 TI - Toxaemia in intestinal obstruction. PMID- 20287051 TI - Blood transfusion. PMID- 20287052 TI - Traumatic rupture of the spleen. PMID- 20287053 TI - Avulsion fracture of the oscalcis. PMID- 20287054 TI - The surgical treatment of deafness. PMID- 20287055 TI - Myoclonic epilepsy. PMID- 20287056 TI - Paroxysmal tachycardia. PMID- 20287057 TI - Roentgenotherapy of cancer of the larynx. PMID- 20287058 TI - Tropical medicine; hemoflagellates. PMID- 20287059 TI - Intra-uterine irradiation; a modification of the radiumhemmet packing method. PMID- 20287060 TI - Reading disabilities in children. PMID- 20287061 TI - The significance of the Rh factor in obstetrics. PMID- 20287062 TI - Pyribenzamine; report on two clinical experiments. PMID- 20287063 TI - The transplantability of autologous mammary tissue in the albino mouse. PMID- 20287064 TI - The blood clotting mechanism; a review. PMID- 20287065 TI - Importance of co-operation between physician and dentist. PMID- 20287066 TI - Child guidance and mother guidance. PMID- 20287067 TI - The treatment of clubfeet. PMID- 20287068 TI - Streptomycin therapy in tuberculosis. PMID- 20287069 TI - The treatment of macrocytic anemia. PMID- 20287070 TI - The surgical treatment of essential hypertension. PMID- 20287071 TI - The treatment of syphilis. PMID- 20287072 TI - The treatment of rheumatic fever. PMID- 20287073 TI - The use of anticoagulants. PMID- 20287074 TI - The treatment of toxemias of pregnancy. PMID- 20287075 TI - Present status of thiouracil therapy. PMID- 20287076 TI - Carcinoma of the fundus arrested for 11 years. PMID- 20287077 TI - A case of hemiplegia treated with prostigmine. PMID- 20287078 TI - A case of nutritional anemia. PMID- 20287079 TI - A case of disseminated Friedlander infection occurring in a post-operative (cesarean section) patient. PMID- 20287080 TI - A case of squamous cell carcinoma in a dermoid cyst of the ovary. PMID- 20287081 TI - Elizabeth Blackwell, the first woman doctor. PMID- 20287082 TI - Report of the Committee on the training and supply of doctors in the event of another war. PMID- 20287083 TI - Private clinics in medical schools. PMID- 20287084 TI - Recent advances in medicine and their effect on premedical needs. PMID- 20287085 TI - Use of the project method in the teaching of histology; a preliminary report. PMID- 20287086 TI - Problems of integration in the medical curriculum. PMID- 20287087 TI - An improved technique for didactic instruction in medicine. PMID- 20287088 TI - Primary atypical pneumonia, etiology unknown; a review of current etiological concepts. PMID- 20287089 TI - Use of radioactive iodine in the treatment of hyperthyroidism. PMID- 20287090 TI - Syphilis in pregnancy. PMID- 20287091 TI - Dysmenorrhea. PMID- 20287092 TI - Functional disorders of menstruation. PMID- 20287093 TI - A history of medicine in Duval County. PMID- 20287094 TI - Bronchogenic adenocarcinoma with metastases; abdominal aneurysm. PMID- 20287095 TI - Obstructive laryngitis in children caused by Hemophilus influenzae bacillus type B. PMID- 20287096 TI - Demerol as a preanesthetic agent. PMID- 20287098 TI - Common dermatologic diseases. PMID- 20287097 TI - An appendix epiploica resembling a vermiform appendix. PMID- 20287099 TI - Orientation in gynecologic uterine bleeding. PMID- 20287100 TI - Roentgenographic aids in carpal scaphoid fractures. PMID- 20287101 TI - A few essentials in prescribing physical medicine in general practice. PMID- 20287102 TI - Psychosomatic diagnosis. PMID- 20287103 TI - Tumors of the parotid. PMID- 20287104 TI - Bacterial endocarditis involving the right side of the heart (a case presentation and clinical review). PMID- 20287106 TI - [Not Available]. PMID- 20287105 TI - The treatment of benign and malignant neoplasms of the skin. PMID- 20287107 TI - [Not Available]. PMID- 20287108 TI - [Not Available]. PMID- 20287109 TI - [Not Available]. PMID- 20287110 TI - [Not Available]. PMID- 20287111 TI - [Not Available]. PMID- 20287112 TI - [Not Available]. PMID- 20287113 TI - [Not Available]. PMID- 20287114 TI - [Not Available]. PMID- 20287115 TI - [Not Available]. PMID- 20287116 TI - [Not Available]. PMID- 20287117 TI - [Not Available]. PMID- 20287118 TI - [Not Available]. PMID- 20287119 TI - [Not Available]. PMID- 20287120 TI - [Not Available]. PMID- 20287121 TI - [Not Available]. PMID- 20287122 TI - [Not Available]. PMID- 20287123 TI - [Not Available]. PMID- 20287124 TI - [Not Available]. PMID- 20287125 TI - [Not Available]. PMID- 20287126 TI - [Not Available]. PMID- 20287127 TI - [Not Available]. PMID- 20287128 TI - [Not Available]. PMID- 20287129 TI - [Not Available]. PMID- 20287131 TI - [Not Available]. PMID- 20287130 TI - [Not Available]. PMID- 20287132 TI - [Not Available]. PMID- 20287133 TI - [Not Available]. PMID- 20287134 TI - [Not Available]. PMID- 20287135 TI - [Not Available]. PMID- 20287136 TI - [Not Available]. PMID- 20287137 TI - [Not Available]. PMID- 20287138 TI - [Not Available]. PMID- 20287139 TI - [Not Available]. PMID- 20287140 TI - A position on the employment of vagotomy in the surgical treatment of peptic ulcer. PMID- 20287141 TI - Severe primary hyperthyroidism with normal basal metabolic rate. PMID- 20287142 TI - Carcinoma of the cecum; successful resection in a 92-year-old man. PMID- 20287143 TI - Thiocyanate goiter; report of a case. PMID- 20287144 TI - The frequency of precancerous lesions in the rectum and colon. PMID- 20287145 TI - Surgical treatment of congenital heart disease; report of a case. PMID- 20287146 TI - Spontaneous compression of both median nerves in the carpal tunnel; six cases treated surgically. PMID- 20287147 TI - Purified precipitated diphtheria toxoid of constant composition. PMID- 20287148 TI - Clinical trials of diphtheria toxoid aluminium-phosphate-precipitated; to determine optional aluminium-phosphate content. PMID- 20287149 TI - Atelectasis after partial gastrectomy. PMID- 20287150 TI - Pain and the healing of peptic ulcers. PMID- 20287151 TI - RECRUITMENT of doctors to the Forces. PMID- 20287153 TI - The nation's food. PMID- 20287152 TI - Part-time nursing. PMID- 20287154 TI - Thyroid and cold sensitivity. PMID- 20287155 TI - Supraspinatus syndrome. PMID- 20287156 TI - Acute porphyria. PMID- 20287157 TI - Conditions in Germany. PMID- 20287158 TI - Some diseases of war and their effects on civil practice. PMID- 20287159 TI - Some consideration in the management of pregnancy toxaemia. PMID- 20287160 TI - CASE of chronic cervicitis and carcinoma of the cervix. PMID- 20287161 TI - Electrolytes and fluids in the treatment of diarrhea in infants. PMID- 20287162 TI - Renal tuberculosis. PMID- 20287163 TI - Pilonidal cysts and sinuses. PMID- 20287164 TI - Urinary infections. PMID- 20287165 TI - Some observations on the surgery of congenital heart disease. PMID- 20287166 TI - Chorionepithelioma; a case report. PMID- 20287167 TI - Congenital cystic lungs in the newborn; a case report with autopsy findings. PMID- 20287168 TI - An anaesthetic estimation of some pre-operative risks. PMID- 20287169 TI - Etiology of jaundice. PMID- 20287170 TI - Accepted laboratory procedure in jaundice. PMID- 20287171 TI - Medical treatment of jaundice. PMID- 20287173 TI - Varicocele. PMID- 20287172 TI - Surgical aspects of jaundice. PMID- 20287174 TI - Anaesthesia in obstetrics. PMID- 20287175 TI - The physiology of refrigeration anesthesia. PMID- 20287176 TI - Radium and X-rays in the treatment of diseases of women. PMID- 20287177 TI - Pneumococcal meningitis in infancy and childhood. PMID- 20287178 TI - Tracheobronchial tuberculosis. PMID- 20287179 TI - A clinical report on benadryl. PMID- 20287180 TI - Ulcerative colitis. PMID- 20287181 TI - A case of spontaneous haemothorax. PMID- 20287182 TI - Traumatic shock. PMID- 20287183 TI - Prostatic calculi. PMID- 20287184 TI - The diagnosis of carcinoma of the pancreas. PMID- 20287185 TI - The smear technique for the diagnosis of uterine carcinoma. PMID- 20287186 TI - [Subacute bacterial endocarditis with brain abscess]. PMID- 20287187 TI - [Carcinoma of the stomach with metastasis]. PMID- 20287188 TI - Acute surgical ascites; a case report. PMID- 20287189 TI - [Myocardial infarction]. PMID- 20287190 TI - Endometriosis; its recognition and clinical diagnosis. PMID- 20287191 TI - A medical practice is a business. PMID- 20287192 TI - The physical properties of artificial radio active isotopes with special reference to their medical applications. PMID- 20287193 TI - Therapeutic applications of the radio-active isotopes. PMID- 20287194 TI - The use of radioactive isotopes as tracers in metabolism. PMID- 20287196 TI - Air evacuation of casualties. PMID- 20287195 TI - Histological localization of radioactive elements; a review. PMID- 20287197 TI - Preliminary report on the use of radio-active phosphorus in Australia. PMID- 20287198 TI - A useful pump. PMID- 20287199 TI - A case of congenital afibrinogenaemia. PMID- 20287200 TI - Post-operative treatment of ruptured appendix. PMID- 20287201 TI - Coronary clotting. PMID- 20287202 TI - The pituitary gland and carbohydrate metabolism. PMID- 20287203 TI - Nasal obstruction in children and its relation to dental development and general health. PMID- 20287204 TI - Dento-facial deformities associated with nasal obstruction. PMID- 20287205 TI - A case of massive haemorrhage from peptic ulceration in a Meckel's diverticulum. PMID- 20287206 TI - Two obscure cases of ascending paralysis. PMID- 20287207 TI - Congenital deformity of the leg. PMID- 20287208 TI - The treatment of thyreotoxicosis by concurrent administration of thiouracil and iodine. PMID- 20287209 TI - The place of manipulative treatment in therapy. PMID- 20287210 TI - Physical medicine and its application to common complaints. PMID- 20287211 TI - Heterospecific pregnancy; the clinical importance of the Rh factor. PMID- 20287212 TI - A case of thrombocytopenic purpura and generalized neuropathy following sulphadiazine therapy. PMID- 20287213 TI - Amoebic pericarditis. PMID- 20287214 TI - Splenic anaemia. PMID- 20287215 TI - Clinical medicine and science. PMID- 20287217 TI - Description of modified apparatus for continuous gastric or duodenal aspiration, with a brief historical review. PMID- 20287216 TI - Cervical and thoracic intervertebral disk disease. PMID- 20287218 TI - A note on the selection of medical students. PMID- 20287219 TI - Poisoning from drinking glycol ethylene. PMID- 20287221 TI - INTERNATIONAL medical conference, London, September 25 to 27, 1946. PMID- 20287220 TI - Report of a case of resistant Haemophilus influenzae meningitis responding to penicillin. PMID- 20287222 TI - The zoological position of man. PMID- 20287223 TI - Peptic ulcer. PMID- 20287224 TI - The treatment of juvenile delinquency. PMID- 20287225 TI - Pre- and post-operative treatment in gastrectomy. PMID- 20287226 TI - The management of the artificial pneumothorax patient. PMID- 20287227 TI - The treatment of fibrositis by physiotherapy. PMID- 20287228 TI - The features and treatment of thyrotoxic heart disease. PMID- 20287229 TI - Bronchiectasis. PMID- 20287230 TI - Radiological diagnosis of bone disease. PMID- 20287231 TI - The intra-mural appendix. PMID- 20287232 TI - Modern diagnosis and treatment of ante-partum haemorrhage. PMID- 20287233 TI - Medicine and ornithology. PMID- 20287234 TI - A post-war survey of venereal disease. PMID- 20287235 TI - Fractures of the nose and zygoma; their recognition and management. PMID- 20287236 TI - The prognosis and treatment of melancholia. PMID- 20287238 TI - Treatment of retinal detachment. PMID- 20287237 TI - The modern treatment of pernicious anaemia. PMID- 20287239 TI - Hypertension: the end. PMID- 20287240 TI - The early diagnosis of pulmonary tuberculosis. PMID- 20287241 TI - The management of carcinoma of the prostate. PMID- 20287242 TI - Intestinal obstruction. PMID- 20287243 TI - The malignancy of intracranial neoplasms. PMID- 20287244 TI - Sulfadiazine block of the kidneys. PMID- 20287245 TI - Peri-sinus abscess complicating acute mastoiditis. PMID- 20287246 TI - Cirrhosis of the liver with primary hepatoma. PMID- 20287247 TI - Paroxysmal ventricular tachycardia complicating acute myocardial infarction. PMID- 20287248 TI - Appendicitis complicating pregnancy. PMID- 20287249 TI - Present status of female sex endocrinology. PMID- 20287250 TI - Peptic ulcer, its etiology and treatment. PMID- 20287251 TI - Rocky Mountain spotted fever. PMID- 20287252 TI - Intramesenteric Meckel's diverticulum. PMID- 20287253 TI - Spinal anesthesia. PMID- 20287254 TI - The modern conception of practical obstetrics. PMID- 20287255 TI - Low back pain. PMID- 20287256 TI - What is the hydrogen ion concentration (pH) of the vagina in Trichomonas vaginalis infestation. PMID- 20287257 TI - Heart disease in Charity Hospital of Louisiana in New Orleans; a survey of 8,313 routine autopsies. PMID- 20287258 TI - Repair of choledochus defect by hepaticoduodenostomy over vitallium tube. PMID- 20287259 TI - Fever of undetermined origin. PMID- 20287260 TI - Cataract surgery as done in India today. PMID- 20287261 TI - The pathologic physiology of diabetes mellitus. PMID- 20287262 TI - Some problems in the field of medical economics. PMID- 20287263 TI - Social and personal responsibilities in medicine. PMID- 20287265 TI - Trends in medical education. PMID- 20287264 TI - Ocular expressions of diabetes. PMID- 20287266 TI - Rehabilitation; the third phase of medical care. PMID- 20287267 TI - The purpuric states. PMID- 20287268 TI - Histoplasmosis case report. PMID- 20287269 TI - Local anesthesia in caesarean section. PMID- 20287270 TI - Psychiatric aspects of pain in the neck. PMID- 20287271 TI - Headaches from otolaryngologic viewpoint; origin and mechanism. PMID- 20287272 TI - Pitfalls in the serologic diagnosis of syphilis. PMID- 20287273 TI - Atresia or stenosis of the nares. PMID- 20287274 TI - Tubal abortion. PMID- 20287275 TI - A plan to eradicate the common cold. PMID- 20287276 TI - Progress in surgery in war and peace. PMID- 20287277 TI - Committee for the Study of Pelvic Cancer. PMID- 20287278 TI - The treatment of brain injuries. PMID- 20287279 TI - Treatment of acne. PMID- 20287280 TI - Common errors in the treatment of fractures, with particular reference to fractures of the extremities. PMID- 20287281 TI - Developmental diagnosis of infant and child; its role in clinical medicine. PMID- 20287283 TI - Treatment of the disorders of speech. PMID- 20287282 TI - Organic variability in heart disease. PMID- 20287284 TI - Disease of the thyroid. PMID- 20287285 TI - Treatment of syphilis with penicillin. PMID- 20287286 TI - VAGUE abdominal pain and leukocytosis. PMID- 20287287 TI - MASSIVE vomiting of blood. PMID- 20287289 TI - The diagnosis and treatment of purpura. PMID- 20287288 TI - Judgment in medicine. PMID- 20287290 TI - A technique of local anesthesia for abdominal operations. PMID- 20287291 TI - Pseudocyesis. PMID- 20287292 TI - Modern treatment of Vincent's infection. PMID- 20287293 TI - Toxaemia of pregnancy, being observations on the prognosis, maternal and foetal, in pre-eclampsia and eclampsia over a period of twenty years in the same general practice. PMID- 20287294 TI - The investigation of prolonged pyrexia. PMID- 20287295 TI - Diagnosis and treatment of chronic deafness. PMID- 20287296 TI - Cancer of the rectum. PMID- 20287297 TI - Thyroid dysfunction in children, its diagnosis, and treatment. PMID- 20287298 TI - The general treatment of skin diseases. PMID- 20287299 TI - The management of the bleeding tonsil. PMID- 20287300 TI - Dentistry in medicine; the differential diagnosis of pain. PMID- 20287301 TI - The present position of carcinoma of the oesophagus. PMID- 20287302 TI - The prolapsed intervertebral disc. PMID- 20287303 TI - Sciatic pain. PMID- 20287304 TI - The place of caesarean section in modern obstetrics. PMID- 20287305 TI - Seborrhoeic dermatitis. PMID- 20287306 TI - Counter-irritation. PMID- 20287308 TI - Electrotherapy in general practice. PMID- 20287307 TI - The role of physical therapy in rheumatic disease. PMID- 20287309 TI - Manipulation in general practice. PMID- 20287310 TI - The role of balneotherapy in rehabilitation. PMID- 20287311 TI - Physiotherapy and the athlete. PMID- 20287312 TI - Twins and triplets, quadruplets and quintuplets. PMID- 20287313 TI - Pain and its problems; cardiac pain. PMID- 20287314 TI - The treatment of congenital pyloric stenosis. PMID- 20287315 TI - The treatment of ringworm. PMID- 20287316 TI - The medical use of DDT. PMID- 20287317 TI - Some obscure and paradoxical problems of syphilis. PMID- 20287318 TI - The complex causes of alcohol addiction. PMID- 20287319 TI - "Hydropic" swelling of renal tubules following intravenous administration of gelatin. PMID- 20287320 TI - Early pathologic changes in skeletal muscle in trichinosis. PMID- 20287321 TI - Congenital teratoid primary carcinoma of the liver. PMID- 20287322 TI - The theory of focal infection; its influence on the practice of medicine. PMID- 20287323 TI - The Institute of Medicine of Chicago; Thirty-first annual report of the Secretary, Dec. 3, 1946. PMID- 20287325 TI - The Central Service for the Chronically Ill; Third annual report of the committee to the Board of Governors of the Institute of Medicine of Chicago, December 10, 1946. PMID- 20287324 TI - Necropsies in the hospitals of Chicago; Twenty-seventh annual report of committee to the Board of Governors of the Institute of Medicine of Chicago, December 10, 1946. PMID- 20287326 TI - The structure and mechanical functioning of the living liver lobules of frogs and rhesus monkeys. PMID- 20287327 TI - The pathologic basis of the clinical manifestations of nephritis. PMID- 20287328 TI - The pathologist's contribution to the clinical interpretation of disorders in the newborn. PMID- 20287329 TI - Release of gas in tissues of animals decompressed from high pressure atmospheres. PMID- 20287330 TI - The fibrous nature of the human cervix and its relation to the isthmic segment in gravid and nongravid uteri. PMID- 20287331 TI - Management of injuries of the spinal cord. PMID- 20287332 TI - A revaluation of splenectomy in thrombocytopenic purpura, based on a 27-year combined clinic follow-up experience. PMID- 20287333 TI - Metabolism of the foodstuffs in experimental diabetes. PMID- 20287334 TI - Diabetes in adults; evidence bearing on the question of whether hyperglycemia is harmful. PMID- 20287335 TI - Juvenile diabetes. PMID- 20287336 TI - Agnogenic myeloid metaplasia of the spleen; report of a case with necropsy studies. PMID- 20287337 TI - Morphologic variability of the myeloma cells in sternal marrow. PMID- 20287338 TI - Infectious hepatitis contrasted with toxic hepatitis. PMID- 20287339 TI - Rh antibodies; clinical-serologic correlation. PMID- 20287342 TI - Some statistics on Rochester babies born in 1944. PMID- 20287340 TI - Acute appendicitis; analysis of 878 cases. PMID- 20287341 TI - Traumatic biliary bronchial fistula with report of two cases due to war wounds. PMID- 20287343 TI - Malaria: a note on its latency and report of a case. PMID- 20287344 TI - A modified ring pinch clamp. PMID- 20287346 TI - Embryologic considerations in surgery of the neck; mediastinal adenoma of a parathyroid gland; report of case. PMID- 20287345 TI - Aberrant gastric mucosa and pancreatic tissue in a bleeding Meckel's diverticulum; report of a case. PMID- 20287347 TI - Embryologic considerations in surgery of the neck; complete lateral cervical (branchial) fistula; report of case. PMID- 20287348 TI - Primary systematized amyloidosis with macroglossia; a syndrome related to Bence Jones proteinuria and myeloma. PMID- 20287349 TI - Cardiac clinics; unusually long survival in the case of a patient with the anginal syndrome of coronary sclerosis and the ultimate development of obliterative arteriosclerosis of the arteries of the legs. PMID- 20287350 TI - Hyperparathyroidism due to diffuse primary hypertrophy and hyperplasia of the parathyroid glands; report of case. PMID- 20287352 TI - Epileptic equivalents. PMID- 20287351 TI - Dissolution of substance of teeth by lemon juice. PMID- 20287353 TI - Wilms' tumor; report of a case with unusual postoperative metastatis. PMID- 20287354 TI - Leiomyoma of the ileum; report of a case. PMID- 20287356 TI - Newcastle virus; conversion of spherical forms to filamentous forms. PMID- 20287355 TI - A fat-soluble material from plasma having the biological activities of biotin. PMID- 20287358 TI - Antigenic structure of Pasteurella pestis and the isolation of a crystalline antigen. PMID- 20287357 TI - Effect of hexaethyl tetraphosphate on choline esterase in vitro and in vivo. PMID- 20287359 TI - Liberation of histamine and heparin by peptone from the isolated dog's liver. PMID- 20287360 TI - Effect of reticulo-endothelial blockade on immunity to the Shwartzman phenomenon. PMID- 20287361 TI - Affinity of avidin for certain analogs of biotin. PMID- 20287362 TI - Hepatorenal factors in circulatory homeostasis; disappearance of hepatic vaso depressor material following intravenous administration. PMID- 20287363 TI - Functional components of the greater superficial petrosal nerve. PMID- 20287364 TI - Employment of the embryonic duck heart for the detection of minute amounts of a digitalis glycoside (lanatoside C). PMID- 20287365 TI - Isolation of pleuropneumonia-like organisms from pathological specimens with the aid of penicillin. PMID- 20287366 TI - Isolation of pleuropneumonia-like organisms from H. influenzae with the aid of penicillin. PMID- 20287367 TI - Infectivity of Trypanosoma cruzi after cultivation for thirteen years in vitro without animal passage. PMID- 20287368 TI - Microscopic historadiographic technic for locating and quantitating radioactive elements in tissues. PMID- 20287369 TI - Infection of mice with tubercle bacilli grown in tween-albumin liquid medium. PMID- 20287370 TI - Alpha naphthylthiourea (ANTU) in dogs; electrophoretic and cholesterol studies on blood plasma and pleural effusion. PMID- 20287371 TI - Folic acid (pteroylglutamic acid) studies; hematologic remissions in pernicious anemia. PMID- 20287372 TI - Effect of frequency of hypothalamic stimulation upon bladder response. PMID- 20287373 TI - Mitotic activity in hypophysis of pregnant rat after injections of estrogen. PMID- 20287374 TI - The use of a resistance wire, strain gauge manometer to measure intraarterial pressure. PMID- 20287375 TI - Sodium cyanide; time of appearance of signs as a function of the rate of injection. PMID- 20287376 TI - Effects of use and disuse on nerve endings, neurosomes, and fiber types in skeletal muscle. PMID- 20287377 TI - Ornithosis in sea-shore birds. PMID- 20287379 TI - Studies on bacterial resistance to streptomycin. PMID- 20287378 TI - Specific complement-fixing diagnostic antigens for Colorado tick fever. PMID- 20287380 TI - Effect of atabrine on auricular fibrillation in the dog. PMID- 20287381 TI - Effect of penicillin on growth and toxin production of enterotoxigenic staphylococci. PMID- 20287382 TI - Studies on thermal sedation in suppression of the symptoms of tetanus toxin. PMID- 20287383 TI - Use of thiosulfate clearance as a measure of glomerular filtration rate in acidotic dogs. PMID- 20287384 TI - Return extrasystoles. PMID- 20287385 TI - Stimulation of sporogenic and nonsporogenic bacteria by traces of penicillin or streptomycin. PMID- 20287386 TI - Studies on auricular tachycardia caused by aconitine administration. PMID- 20287387 TI - A method for intrathoracic operation on the rat. PMID- 20287388 TI - Intravascular and intracardiac pressure recording in man; electrical apparatus compared with the Hamilton manometer. PMID- 20287389 TI - Evidence that virus of herpes simplex does not cause Vincent's angina of the tonsil. PMID- 20287390 TI - Effects of some old and proposed anticonvulsants on the threshold for electrical convulsions. PMID- 20287391 TI - Isopropyl alcohol, other ketogens, and miscellaneous agents on thresholds for electrical convulsions and diphenylhydantoin. PMID- 20287392 TI - Hydropic changes in pancreatic ductules and islets in alloxan diabetes in the rabbit. PMID- 20287393 TI - Antibacterial action of N-alkyl p-aminobenzoic acid derivatives. PMID- 20287394 TI - Action of certain carbohydrates on the reaction of Eberthella typhosa with antibody O. PMID- 20287395 TI - Influence of nitrogen mustards on the antibody response. PMID- 20287396 TI - Chemotherapeutic action of streptomycin and of streptomycin with a sulfone or sulfadiazine on tuberculosis. PMID- 20287397 TI - Further studies on the testing of sterility of concentrated streptomycin solutions. PMID- 20287398 TI - Changes in the precordial electrocardiogram due to the position of the exploring electrode. PMID- 20287399 TI - The mission of a medical school. PMID- 20287401 TI - Functional uterine bleeding. PMID- 20287402 TI - The etiology of Colorado tick fever and an immunological comparison to dengue. PMID- 20287400 TI - Induction of artificial pneumothorax; a method of utilizing pulmonary puncture. PMID- 20287404 TI - Dynamic and therapeutic features of 17 cases of so-called psychogenic asthma. PMID- 20287403 TI - The diagnosis of rheumatic fever in children. PMID- 20287405 TI - The management of hyperthyroidism. PMID- 20287406 TI - Coccidioidomycosis and the chest roentgenogram. PMID- 20287407 TI - Clinical experience with methergine, a new oxytocic. PMID- 20287408 TI - Clinical observations with methergine, a partial synthetic oxytocic. PMID- 20287409 TI - Metatarsalgia; painful foot, Morton's syndrome, March fracture; a physiologic entity. PMID- 20287410 TI - The attainment of poise. PMID- 20287411 TI - Chemotherapy. PMID- 20287412 TI - Haemolytic disease of the newborn; a report on a series of seventeen consecutive cases. PMID- 20287413 TI - A case of recovery from methyl salicylate poisoning. PMID- 20287415 TI - Caudal analgesia; a method of control of pain and hemorrhagia in childbirth. PMID- 20287414 TI - The carcinogenic action of hormones. PMID- 20287416 TI - Carcinoma of the colon. PMID- 20287418 TI - The Army Medical Library. PMID- 20287417 TI - Religion and psychiatry. PMID- 20287419 TI - Diagnosis and treatment of the anemias. PMID- 20287420 TI - Penicillin therapy in congenital syphilis. PMID- 20287421 TI - Hypo-Leydigism and hypopituitarism. PMID- 20287422 TI - Perianal and perirectal infections. PMID- 20287423 TI - Uterosalpinography; report of a fatality. PMID- 20287425 TI - Problems of congenital cataracts. PMID- 20287424 TI - X-ray exposure meters and automatic exposure timers. PMID- 20287426 TI - Congenital anomalies following maternal rubella. PMID- 20287427 TI - Present status of knowledge concerning etiology of primary atypical pneumonia. PMID- 20287428 TI - Congenital atresia of the esophagus with tracheo-esophageal fistula. PMID- 20287429 TI - Physiological changes during spinal anesthesia. PMID- 20287430 TI - A review of 9,000 obstetrical cases at the Harris Memorial Methodist Hospital, Fort Worth, Texas. PMID- 20287431 TI - How innocent is the ordinary nonpigmented mole? PMID- 20287432 TI - The surgical treatment of bronchiectasis; role of penicillin in postoperative care. PMID- 20287434 TI - Pseudo-mastoiditis. PMID- 20287435 TI - The treatment of the pre-fibrotic liver with ascites; report of a case. PMID- 20287433 TI - The application of the principles of early ambulation to surgical patients. PMID- 20287438 TI - Hemorrhage in putrid lung abscess. PMID- 20287436 TI - Acute appendicitis, with a case report. PMID- 20287437 TI - The choice of forceps. PMID- 20287439 TI - Renal aspects of hypertensive disease. PMID- 20287440 TI - Filarial infections. PMID- 20287441 TI - The organization of mental hygiene interest in a State and its effective use. PMID- 20287442 TI - Reconstructive surgery in an Army general hospital. PMID- 20287444 TI - [Not Available]. PMID- 20287445 TI - [Not Available]. PMID- 20287446 TI - [Not Available]. PMID- 20287443 TI - [Not Available]. PMID- 20287448 TI - [Not Available]. PMID- 20287447 TI - [Not Available]. PMID- 20287449 TI - [Not Available]. PMID- 20287450 TI - [Not Available]. PMID- 20287451 TI - [Not Available]. PMID- 20287452 TI - [Not Available]. PMID- 20287453 TI - [Not Available]. PMID- 20287454 TI - [Not Available]. PMID- 20287455 TI - [Not Available]. PMID- 20287456 TI - [Not Available]. PMID- 20287457 TI - [Not Available]. PMID- 20287458 TI - [Not Available]. PMID- 20287459 TI - [Not Available]. PMID- 20287460 TI - [Not Available]. PMID- 20287461 TI - [Not Available]. PMID- 20287462 TI - [Not Available]. PMID- 20287463 TI - [Not Available]. PMID- 20287464 TI - [Not Available]. PMID- 20287465 TI - [Not Available]. PMID- 20287466 TI - [Not Available]. PMID- 20287467 TI - [Not Available]. PMID- 20287469 TI - [Not Available]. PMID- 20287468 TI - [Not Available]. PMID- 20287470 TI - [Not Available]. PMID- 20287471 TI - [Not Available]. PMID- 20287472 TI - [Not Available]. PMID- 20287473 TI - [Not Available]. PMID- 20287474 TI - [Not Available]. PMID- 20287475 TI - [Not Available]. PMID- 20287476 TI - [Not Available]. PMID- 20287477 TI - [Not Available]. PMID- 20287478 TI - [Not Available]. PMID- 20287479 TI - [Not Available]. PMID- 20287480 TI - [Not Available]. PMID- 20287481 TI - [Not Available]. PMID- 20287483 TI - [Not Available]. PMID- 20287482 TI - [Not Available]. PMID- 20287484 TI - [Not Available]. PMID- 20287486 TI - [Not Available]. PMID- 20287485 TI - [Not Available]. PMID- 20287488 TI - [Not Available]. PMID- 20287487 TI - [Not Available]. PMID- 20287489 TI - [Not Available]. PMID- 20287491 TI - New methods for the control of air-borne infection with especial reference to the use of triethylene glycol vapor. PMID- 20287492 TI - Injuries due to cold, with particular reference to frostbite and trench foot. PMID- 20287490 TI - [Not Available]. PMID- 20287493 TI - Propylthiouracil. PMID- 20287494 TI - Health in the older age groups. PMID- 20287495 TI - The laboratory diagnosis of tuberculosis. PMID- 20287496 TI - RAFT survival of a P-5l pilot. PMID- 20287497 TI - ELLIS flotation stretcher. PMID- 20287498 TI - Hygiene problems of the campaign in North-West Europe, 1944-45; a review. PMID- 20287499 TI - Hospital construction. PMID- 20287500 TI - Operation, M. O. PMID- 20287501 TI - Amoeboma or carcinoma of the rectum? PMID- 20287503 TI - Program for the deaf. PMID- 20287502 TI - Future research in aviation medicine. PMID- 20287504 TI - Recent experiences in the treatment of kala-azar. PMID- 20287505 TI - The dental program of the Veterans Administration. PMID- 20287506 TI - The Medical Consultants Division of the Surgeon General's Office. PMID- 20287507 TI - Sanitary corps functions and organization. PMID- 20287508 TI - Amputations; the care of amputee patients. PMID- 20287509 TI - Enteric protozoa and helminth findings as influenced in the war years. PMID- 20287510 TI - Neuropsychiatry at a separation center. PMID- 20287511 TI - Health of the Army. PMID- 20287512 TI - Environment and fatal heat stroke; an analysis of 157 cases occurring in the Army in the U.S. during World War II. PMID- 20287513 TI - Relation historical and surgical, of the expedition of the Army of the Orient, in Egypt and in Syria [transl. Rose Alexander]. PMID- 20287514 TI - Coconut shells as an industrial raw material; coconut shell charcoal; activated carbon. PMID- 20287515 TI - Eradication of insect pests of stored grains rather than their control. PMID- 20287516 TI - A simple inexpensive hand-microtome. PMID- 20287517 TI - A micro-glass electrode for pH determination. PMID- 20287518 TI - A note on mosaic virus of sann-hemp (Crotalaria juncea Linn.) and its its crystallisation. PMID- 20287519 TI - Some factors affecting the refractive index and constant of milk. PMID- 20287520 TI - Initiation of lactation in heifers and cows. PMID- 20287521 TI - Chromosome numbers in Sesbania spp. PMID- 20287522 TI - An early Cherokee ethnobotanical note. PMID- 20287523 TI - A new species of Culex from New Guinea (Diptera, Culicidae). PMID- 20287524 TI - A kinetic theory of liquids. PMID- 20287525 TI - Origin of erythrocytes. PMID- 20287526 TI - Constitution of strychnine and its relation to cinchonine. PMID- 20287527 TI - Absolute values of the rates of unimolecular reactions. PMID- 20287528 TI - Diffraction of light by high-frequency ultrasonic waves. PMID- 20287529 TI - Relationships between the assemblages of plants fed upon by different insects, and between the assemblages of insects that feed upon different plants. PMID- 20287530 TI - Detoxicating effect of verdoperoxidase on toxins. PMID- 20287531 TI - Curative effects of a complex choline compound on the impaired metabolism of choline-deficient rats. PMID- 20287532 TI - Digestibility of cow's and buffalo's milk. PMID- 20287533 TI - Rancidity in Indian butter fat (ghee). PMID- 20287534 TI - Respiration of developing anthers. PMID- 20287537 TI - The construction and performance of a large grating monochromator with a high energy output for photochemical and biological investigations. PMID- 20287538 TI - Measurement of small currents; characteristics of types 38, 954, and 959 as reduced grid current tubes. PMID- 20287539 TI - A one-shot multivibrator anticoincidence and recording circuit. PMID- 20287540 TI - Improvement of the characteristics of photo-voltaic and photo-conductive cells by feedback circuits. PMID- 20287541 TI - An instrument to measure servomechanism performance. PMID- 20287542 TI - Hydrogen recoil proportional counter for neutron detection. PMID- 20287543 TI - A recording vacuum grating spectrometer for the infra-red. PMID- 20287544 TI - Speed control for the air-driven centrifuge. PMID- 20287545 TI - A mechanical switch for use in some bioelectric measurements. PMID- 20287546 TI - Vacuum valve. PMID- 20287547 TI - A level and differential attenuator. PMID- 20287548 TI - Protective device for oil diffusion pumps. PMID- 20287549 TI - Biochemical analyses with the Spekker absorptiometer; estimation of urea, citrulline, allantoin and related carbamido compounds. PMID- 20287550 TI - The mechanism of the formation of allophanates from carbamates. PMID- 20287551 TI - Studies on ureides; the chemistry of thiuret and related compounds. PMID- 20287552 TI - Evidence for a mitotic hormone; observations on the mitoses of the embryo-sac of Fritilla ria imperiatis. PMID- 20287553 TI - Alumni appraisal of psychiatric education. PMID- 20287554 TI - Psychiatry in medical education; the teacher-characteristics and qualifications. PMID- 20287555 TI - What should be taught. PMID- 20287556 TI - The genetics of epilepsy. PMID- 20287557 TI - The neuropsychiatric program of the Veterans Administration. PMID- 20287558 TI - Care and treatment of the psychiatric patient in the Veterans Administration. PMID- 20287559 TI - The neuropsychiatric training program of the Veterans Administration. PMID- 20287560 TI - The new role of psychological testing in psychiatry. PMID- 20287561 TI - The psychoanalytical approach to the masculine and feminine principles in music. PMID- 20287562 TI - Dilantin treatment for behavior problem children with abnormal electroencephalograms. PMID- 20287563 TI - Racial aspects of emotional problems of Negro soldiers. PMID- 20287564 TI - Mental illness among Negro troops overseas. PMID- 20287565 TI - Review of psychiatric progress, 1946. PMID- 20287566 TI - Neuropathology, biochemistry and endocrinology. PMID- 20287567 TI - Electroencephalography. PMID- 20287568 TI - Epilepsy. PMID- 20287569 TI - Neurosyphilis. PMID- 20287570 TI - Alcohol; geriatrics. PMID- 20287571 TI - Child psychiatry; mental deficiency. PMID- 20287572 TI - Psychometrics. PMID- 20287573 TI - General clinical psychiatry, psychosomatic medicine and psychosurgery. PMID- 20287574 TI - Physiological treatment of psychoses. PMID- 20287575 TI - Family care and out-patient mental clinics in 1946. PMID- 20287576 TI - Psychiatric nursing. PMID- 20287577 TI - Psychiatric social work. PMID- 20287578 TI - Occupational therapy. PMID- 20287579 TI - Psychiatry in industry. PMID- 20287580 TI - Administrative, forensic and military psychiatry. PMID- 20287581 TI - Psychiatric education. PMID- 20287582 TI - [Not Available]. PMID- 20287583 TI - [Not Available]. PMID- 20287584 TI - [Not Available]. PMID- 20287585 TI - [Not Available]. PMID- 20287586 TI - [Not Available]. PMID- 20287587 TI - [Not Available]. PMID- 20287588 TI - [Not Available]. PMID- 20287589 TI - [Not Available]. PMID- 20287590 TI - [Not Available]. PMID- 20287591 TI - [Not Available]. PMID- 20287592 TI - [Not Available]. PMID- 20287593 TI - [Not Available]. PMID- 20287594 TI - [Not Available]. PMID- 20287595 TI - [Not Available]. PMID- 20287596 TI - [Not Available]. PMID- 20287597 TI - [Not Available]. PMID- 20287598 TI - [Not Available]. PMID- 20287599 TI - [Not Available]. PMID- 20287600 TI - [Not Available]. PMID- 20287601 TI - [Not Available]. PMID- 20287602 TI - [Not Available]. PMID- 20287603 TI - [Not Available]. PMID- 20287604 TI - [Not Available]. PMID- 20287605 TI - [Not Available]. PMID- 20287606 TI - [Not Available]. PMID- 20287607 TI - [Not Available]. PMID- 20287608 TI - [Not Available]. PMID- 20287609 TI - [Not Available]. PMID- 20287610 TI - [Not Available]. PMID- 20287612 TI - [Not Available]. PMID- 20287613 TI - [Not Available]. PMID- 20287611 TI - [Not Available]. PMID- 20287614 TI - [Not Available]. PMID- 20287617 TI - [Not Available]. PMID- 20287615 TI - [Not Available]. PMID- 20287618 TI - [Not Available]. PMID- 20287616 TI - [Not Available]. PMID- 20287619 TI - [Not Available]. PMID- 20287620 TI - [Not Available]. PMID- 20287621 TI - [Not Available]. PMID- 20287622 TI - [Not Available]. PMID- 20287624 TI - [Not Available]. PMID- 20287623 TI - [Not Available]. PMID- 20287625 TI - [Not Available]. PMID- 20287626 TI - Volume flow of blood through the human brain. PMID- 20287628 TI - Abreaction in the military setting. PMID- 20287627 TI - Relation of acute mucosal hemorrhages and ulcers of gastrointestinal tract to intracranial lesions. PMID- 20287629 TI - Neurogenic arthropathy (Charcot joint) associated with diabetic neuropathy; report of two cases. PMID- 20287631 TI - Schistosomiasis of the brain due to Schistosoma japomcum; report of a case. PMID- 20287630 TI - Metastases of uterine carcinoma to the central nervous system; a clinicopathologic study. PMID- 20287632 TI - Electroencephalogram in the pitressin hydration test for epilepsy. PMID- 20287633 TI - Abdominal rigidity; a symptom of concussion of the spinal cord. PMID- 20287634 TI - Parenchymatous cerebellar degeneration; report of two cases. PMID- 20287635 TI - Progressive nuclear ophthalmoplegia, possibly on the basis of a vitamin deficiency; report of a case. PMID- 20287636 TI - Treatment of spasmodic torticollis; report of two cases. PMID- 20287637 TI - Factors causing mass spasms after transection in the cord in man; a reexamination. PMID- 20287638 TI - Brain tumor; report of two cases. PMID- 20287639 TI - Encephalomalacia of the cerebellum and temporosphenoid lobe; report of a case. PMID- 20287640 TI - Traumatic hematomyelia with unusual features. PMID- 20287641 TI - Value of penicillin in treatment of neurosyphilis. PMID- 20287642 TI - Myelination of the central nervous system of Natrix sipedon. PMID- 20287643 TI - The problem of disseminated sclerosis. PMID- 20287644 TI - Heredo-degenerative hemiballismus; a contribution to the question of primary atrophy of the corpus luysii. PMID- 20287646 TI - Traumatic amnesia. PMID- 20287647 TI - The pupillo-constrictor pathway and the nerves to the ocular muscles in man. PMID- 20287645 TI - Striatal and pyramidal lesions in the cat. PMID- 20287648 TI - Injury activity and trigger zones in human nerves. PMID- 20287649 TI - On simultaneous bilateral stimulation of the body in a lesion of the parietal lobe. PMID- 20287650 TI - Diagnostic evaluation of early schizophrenia. PMID- 20287651 TI - Serratus magnus palsy; with report of five cases. PMID- 20287652 TI - Psychosynthesis of amnesia; report of two cases treated by hypnosis. PMID- 20287654 TI - A study in attempted suicide. PMID- 20287653 TI - The growth concept of nervous integration; on imagined hearing; second contribution to a new theory of hearing; a proposed solution for the dilemma of taste-physiology; the integrative function of the tractus solitarius and its relation to the ego, superego and Id systems; summary of the growth concept of nervous integration. PMID- 20287655 TI - A study of suicidal soldiers in the European Theatre after V-E day. PMID- 20287657 TI - Psychosurgery, 1936-1946. PMID- 20287656 TI - Neuropsychiatric services in the E. T. O. PMID- 20287658 TI - Electroencephalography as a prognostic aid in severe head injury. PMID- 20287659 TI - On being a literary executor. PMID- 20287660 TI - A nutritional study of neurosurgical patients; with special reference to nitrogen balance and convalescence in the postoperative period. PMID- 20287661 TI - Nerve end separation following suture; resection of the neck of the fibula in suture of the peroneal nerve. PMID- 20287662 TI - Surgical treatment of angina pectoris. PMID- 20287663 TI - The care and rehabilitation of patients with injuries of the spinal cord and cauda equina; a preliminary report on 113 cases. PMID- 20287664 TI - Observations on the use of tantalum foil in peripheral nerve surgery. PMID- 20287665 TI - Cerebral schistosomiasis; report of a case with surgical removal of an intracerebral mass of schistosomal ova. PMID- 20287666 TI - Extraspinal lumbar meningocele. PMID- 20287670 TI - Emotional disturbances in epileptic children. PMID- 20287668 TI - A successful autogenous graft for radial nerve paralysis; case report. PMID- 20287674 TI - Idiopathic epilepsy in childhood. PMID- 20287667 TI - Electroencephalographic studies after ligation of the internal carotid artery. PMID- 20287672 TI - Children's expressed attitudes toward their epilepsy. PMID- 20287669 TI - Neuropathology of epilepsy in children. PMID- 20287677 TI - Treatment of the convulsive child in a children's psychiatric hospital. PMID- 20287673 TI - Drug therapy for epileptic children. PMID- 20287671 TI - Rorschach psychodiagnosis in a group of epileptic children. PMID- 20287676 TI - The treatment of institutionalized epileptic children. PMID- 20287675 TI - Observations on the treatment of recurring convulsions. PMID- 20287683 TI - New methods of treatment for venereal disease; syphilis. PMID- 20287678 TI - Residential schools for epileptic children in England. PMID- 20287680 TI - The epileptic child and the public school (report on the Baltimore project). PMID- 20287682 TI - Nutrition in a public health program. PMID- 20287679 TI - The care of the epileptic child in residential schools in America. PMID- 20287684 TI - Bedside nursing; an essential service. PMID- 20287688 TI - How to raise efficiency and reduce accidents in industry. PMID- 20287681 TI - The vocational problem of the epileptic child. PMID- 20287686 TI - Nursing in China. PMID- 20287687 TI - The nurse in a health education program. PMID- 20287689 TI - The development in the care of the injured workman in Massachusetts. PMID- 20287690 TI - South Carolina tuberculosis control program in industry. PMID- 20287685 TI - The late cancer case. PMID- 20287691 TI - Visiting nursing in industry. PMID- 20287697 TI - Learning by seeing; a scries of photographs of museum specimens; the respiratory system. PMID- 20287695 TI - The importance of breast feeding. PMID- 20287693 TI - The value of pre-employment physical examination in our safety program. PMID- 20287698 TI - The diagnosis of diseases of the lungs. PMID- 20287694 TI - These are your problems. PMID- 20287692 TI - First aid in industrial dental injuries. PMID- 20287696 TI - Total laryngectomy. PMID- 20287699 TI - Infant feeding; breast feeding. PMID- 20287704 TI - [Not Available]. PMID- 20287703 TI - [Not Available]. PMID- 20287705 TI - [Not Available]. PMID- 20287701 TI - [Not Available]. PMID- 20287700 TI - Learning by seeing; a series of photographs of museum specimens; the respiratory system. PMID- 20287702 TI - [Not Available]. PMID- 20287708 TI - [Not Available]. PMID- 20287706 TI - [Not Available]. PMID- 20287709 TI - [Not Available]. PMID- 20287707 TI - [Not Available]. PMID- 20287710 TI - [Not Available]. PMID- 20287711 TI - [Not Available]. PMID- 20287713 TI - [Not Available]. PMID- 20287712 TI - [Not Available]. PMID- 20287714 TI - [Not Available]. PMID- 20287718 TI - [Not Available]. PMID- 20287715 TI - [Not Available]. PMID- 20287716 TI - [Not Available]. PMID- 20287717 TI - [Not Available]. PMID- 20287719 TI - [Not Available]. PMID- 20287720 TI - [Not Available]. PMID- 20287721 TI - [Not Available]. PMID- 20287726 TI - Relapsing and chronic ocular lesions following mustard gas (dichloroethyl sulfide) burns. PMID- 20287725 TI - Surgical treatment of primary glaucoma. PMID- 20287723 TI - [Not Available]. PMID- 20287727 TI - A squint syndrome. PMID- 20287724 TI - Surgical methods of treating paralysis of the superior oblique muscle. PMID- 20287722 TI - [Not Available]. PMID- 20287728 TI - Dermatomyositis with retinopathy; report of a case. PMID- 20287729 TI - Pharmacologic action of some ophthalmic drugs. PMID- 20287730 TI - Stability of penicillin in ophthalmic solutions. PMID- 20287732 TI - The capillary sphincter in the human retina. PMID- 20287735 TI - Arachnoiditis. PMID- 20287734 TI - New modification of the McReynolds transplantation for pterygium. PMID- 20287731 TI - Marginal myotomy; analysis of twenty-two cases. PMID- 20287733 TI - Removal of deeply embedded foreign bodies from the cornea. PMID- 20287737 TI - Cyclopia. PMID- 20287741 TI - Associated systemic factors in retinitis pigmentosa. PMID- 20287742 TI - Use of frozen-dried cornea as transplant material. PMID- 20287743 TI - Modified corneal incision with iridodialysis and iridectomy for opening the anterior chamber angle. PMID- 20287747 TI - Pseudo-Graefe phenomenon. PMID- 20287736 TI - Exophthalmos and associated ocular disturbances in hyperthyroidism. PMID- 20287740 TI - Clinical disturbances of the oculomotor system. PMID- 20287745 TI - Complete unilateral ophthalmoplegia due to primary carcinoma of the sphenoidal sinus; sphenoidal fissure-optic canal syndrome with complete ophthalmoplegia; report of a case. PMID- 20287738 TI - Controversial points in ocular penicillin therapy. PMID- 20287746 TI - Treatment of late postoperative intraocular infections with intraocular injection of penicillin. PMID- 20287739 TI - Lipid dystrophy of the cornea. PMID- 20287744 TI - Hemifacial spasm; report of two cases. PMID- 20287748 TI - Buphthalmos in a six month premature infant. PMID- 20287750 TI - Sensorial retinal relationship in concomitant strabismus. PMID- 20287749 TI - Pathogenesis of glaucoma and glaucomatous atrophy of the optic nerve. PMID- 20287752 TI - Primary tuberculosis of the conjunctiva. PMID- 20287751 TI - Congenital vertical motor pareses. PMID- 20287753 TI - Contributions to the technic of corneal grafting. PMID- 20287754 TI - Bench for the teaching of ophthalmic optics. PMID- 20287755 TI - Clinical significance of the postnasal space. PMID- 20287756 TI - Surgery for paralysis of the external rectus muscle. PMID- 20287757 TI - The role of mechanical and anatomical factors in the problem of tonsillar foci. PMID- 20287758 TI - On the relationship between radiological appearances and proofpuncture findings in suspected cases of infection of the maxillary antrum. PMID- 20287759 TI - Case of bilateral frontal sinusitis, with osteomyelitis of the frontal bone and left antral sinusitis, treated with penicillin. PMID- 20287760 TI - A case of respiratory inco-ordination. PMID- 20287761 TI - Discussion on the chemotherapy of meningitis secondary to infection of the ear and nasal sinuses. PMID- 20287762 TI - Principles of nomenclature and of classification of speech and voice disorders. PMID- 20287763 TI - Sex differences in relation to stuttering. PMID- 20287764 TI - Intensive group therapy in speech rehabilitation. PMID- 20287765 TI - A group pure tone hearing test. PMID- 20287766 TI - Contact ulcer of the larynx; history. PMID- 20287767 TI - A preliminary investigation in the testing of lip reading achievement. PMID- 20287768 TI - Reading and arithmetic abilities associated with speech defects. PMID- 20287769 TI - Problems in cerebral palsy. PMID- 20287770 TI - The stutterer acts it out. PMID- 20287771 TI - A review of the available literature on the pharynx and pharyngeal surgery for 1945. PMID- 20287772 TI - Physical characteristics of hearing aids. PMID- 20287773 TI - Hearing aid clinics in England. PMID- 20287774 TI - Periesophagitis. PMID- 20287775 TI - The development of recorded auditory tests for measuring hearing loss for speech. PMID- 20287776 TI - What we can do for our tracheotomized patients. PMID- 20287777 TI - A method of obtaining secretions from nasopharynx for diagnosis of nasal allergy (particularly useful in dry noses). PMID- 20287778 TI - The aetiology of tropical ulcers in Somalis. PMID- 20287779 TI - The plasma antimony concentration and the urinary antimony excretion in man during therapy with organic antimony compounds. PMID- 20287780 TI - Field tests on some pyrethrum anti-mosquito repellent creams against woodland species of Aedes in Britain. PMID- 20287781 TI - The evaluation of culture mediums for the routine isolation of the gonococcus. PMID- 20287782 TI - Observation on the direct oxidase test as applied to gonococcic colonies grown in certain mediums. PMID- 20287783 TI - Syphilitic nephrosis; a report of two cases. PMID- 20287785 TI - Personal names among the Bari. PMID- 20287784 TI - The Royal Institute for the Indies and its ethnological work. PMID- 20287786 TI - Electrocardiographic changes in fulminating anoxia. PMID- 20287787 TI - The motivations of the flyer and his reactions to the stresses of flight. PMID- 20287789 TI - Auditory deterioration in airline pilots. PMID- 20287788 TI - Study of the relation between Minnesota multiphasic personality inventory scores and pilot error in aircraft accidents. PMID- 20287790 TI - Aerotitis media; a brief presentation of its symptomatology, prevention and treatment. PMID- 20287791 TI - Aviation medicine and physical standards for airmen. PMID- 20287792 TI - Notes on Japanese aviation medicine and research. PMID- 20287793 TI - Aero medical experiences in China. PMID- 20287794 TI - The physiology of pressure breathing; a brief review of its present status. PMID- 20287795 TI - Studies on altitude decompression sickness; attempts to avoid decompression sickness by selection of resistant personnel. PMID- 20287796 TI - The effect of positive radial acceleration on the intrarectal pressure. PMID- 20287797 TI - The effect of binding of the abdomen and thorax on pulmonary lesions produced by explosive decompression. PMID- 20287798 TI - On the identity of the cotton capsid of Uganda. PMID- 20287799 TI - The insect parasites of the carrot fly, Psilarosae, Fab. PMID- 20287800 TI - Physiological and ecological studies on the species of Capnodis in Palestine (Col., Buprestidae); toxicological studies. PMID- 20287801 TI - General observations on mosquitos in relation to yellow fever in the Anglo Egyptian Sudan. PMID- 20287802 TI - The use of residual films of DDT and gammexane in malaria control. PMID- 20287803 TI - The excitant and repellent effects on mosquitos of sub-lethal contacts with DDT. PMID- 20287804 TI - Aphanus (Hem., Lygaeidae) in stored gound-nuts. PMID- 20287805 TI - The eradication of Simulium neavei, Roubaud, from an onchocerciasis area in Kenya Colony. PMID- 20287806 TI - A chalcidoid egg-parasite of an Australian buprestid. PMID- 20287807 TI - Is salt a preservative? PMID- 20287808 TI - Does Paramecium encyst? PMID- 20287810 TI - Fact and fancy in biochemistry. PMID- 20287809 TI - Detection of obstacles by blindfolded persons. PMID- 20287811 TI - An obstacle detecting device for the blind. PMID- 20287812 TI - An adaptation of the standard photofluorometric analysis to the estimation of thiamine in plants. PMID- 20287813 TI - Present knowledge of the vitamin B complex. PMID- 20287814 TI - Which regression? PMID- 20287815 TI - An approximate distribution of estimates of variance components. PMID- 20287816 TI - Preliminary report on the rectangular lattices. PMID- 20287817 TI - The variance of the overlap of geometrical figures with reference to a bombing problem. PMID- 20287819 TI - The generalisation of student's problems when several different population variances are involved. PMID- 20287818 TI - A study of a first dynasty series of Egyptian skulls from Sakkara and of an eleventh dynasty series from Thebes. PMID- 20287820 TI - The distribution of Kendall's tau coefficient of rank correlation in rankings containing ties. PMID- 20287821 TI - The use of range in place of standard deviation in the tau-test. PMID- 20287822 TI - The frequency distribution of square root b1 for samples of all sizes drawn at random from a normal population. PMID- 20287823 TI - On the computation of universal moments of tests of statistical normality derived from samples drawn at random from a normal universe; application to the calculation of the seventh moment of b2. PMID- 20287824 TI - The asymptotical distribution of range in samples from a normal population. PMID- 20287825 TI - Limits of the ratio of mean range to standard deviation. PMID- 20287826 TI - Significance tests for 2 X 2 tables. PMID- 20287827 TI - The choice of statistical tests illustrated on the interpretation of data classed in a 2 X 2 table. PMID- 20287828 TI - Decline in regenerative capacity of the Platypoecilus maculatus gonopodium during its morphogenesis. PMID- 20287829 TI - On the cytoplasmic elements in the midgut epithelium of the larvae of Drosophila melanogaster Meigen. PMID- 20287830 TI - The development of the shoulder region of the turtle, Chrysemys picta marginata, with special reference to the primary musculature. PMID- 20287831 TI - The anatomy and histology of the alimentary tract of the plankton-feeder, Atherina forskali Rupp. PMID- 20287832 TI - Theories of amoeboid movement. PMID- 20287833 TI - The mechanism of inhibition of cellular activity by narcotics. PMID- 20287834 TI - Hypervolemia secondary to grafted granulosa-cell tumor. PMID- 20287836 TI - Observations on the immediate response of Paramecium to mixtures of aerosol acetone-methylcholanthrene. PMID- 20287835 TI - Blood uric acid and proteose, body temperature, and glomerular clearance of rabbits implanted with the Brown-Pearce carcinoma and treated with the polysaccharide from Serratia marcescens. PMID- 20287837 TI - Avenues of approach to the gastric-cancer problem. PMID- 20287838 TI - Effect of prolonged ingestion of thiourea on mammary glands and the appearance of mammary tumors in adult C3H mice. PMID- 20287839 TI - Response of certain mouse tumors to bis (beta-chloroethyl) sulfide (mustard gas). PMID- 20287840 TI - Cultivation of tumors in the anterior chambers of the eyes of guinea pigs. PMID- 20287841 TI - The metabolism of sulphonamides; the detection of 3-hydroxysulphanilamide in the urine of hospital patients treated with sulphanilamide. PMID- 20287844 TI - Metabolic processes in the gastric mucosa. PMID- 20287846 TI - The action of sulphites on the cystine disulphide linkages of wool: the effect of some chemical modifications of the wool on the magnitude of the bisulphite reactive fraction (A + B) and the relative magnitudes of subfractions A and B. PMID- 20287848 TI - The excretion of 1 (--)-tyrosine in urine. PMID- 20287850 TI - British anti-lewisite; antidotal effects against therapeutic arsenicals. PMID- 20287854 TI - Reactivation by dithiols of enzymes inhibited by lewisite. PMID- 20287858 TI - Studies in vitamin A; a chromatographic method for separating free and esterified vitamin A. PMID- 20287859 TI - Studies in vitamin A; the relationship between blood vitamin A levels and liver stores in rats. PMID- 20287861 TI - Experiments on the localization and nature of tea oxidase. PMID- 20287863 TI - Intercelular hormones; release and synthesis of factors of the vitamin B complex by damaged living cells. PMID- 20287864 TI - Intercellular hormones; release of amino-acids by damaged living yeast cells. PMID- 20287865 TI - Intercellular hormones; release of nucleotides and nucleosides by damaged living cells. PMID- 20287868 TI - Assay of essential metabolites. PMID- 20287869 TI - Some principles in the use of microbiological methods; the types of response measured and their relationship to substances being determined. PMID- 20287870 TI - Statistical aspects of microbiological assays. PMID- 20287871 TI - The use of enzyme preparations from bacteria for the estimation of amino-acids. PMID- 20287872 TI - Estimation of amino-acids by the microbiological technique. PMID- 20287873 TI - The microbiological estimation of B vitamins. PMID- 20287874 TI - Genetic techniques in the development of microbiological assays. PMID- 20287875 TI - Methods for the assay of antibiotics. PMID- 20287876 TI - The assay of antitoxins. PMID- 20287877 TI - Suggestions for a mathematical biophysics of some psychoses. PMID- 20287878 TI - A problem in the mathematical biophysics of interaction of two or more individuals which may be of interest in mathematical sociology. PMID- 20287879 TI - Mathematical theory of motivation; interactions of two individuals. PMID- 20287880 TI - The mechanism of the middler ear; the two piston problem. PMID- 20287881 TI - Low-temperature calorimetry at the Bartlesville Station of the Bureau of Mines. PMID- 20287882 TI - The use of organocadmium reagents for the preparation of ketones. PMID- 20287883 TI - The chemical composition of barks. PMID- 20287885 TI - Anomalous nitration reactions. PMID- 20287886 TI - The chemistry of sodium phosphates. PMID- 20287887 TI - Application of thioglycolic acid to the spectrophotometric determination of iron in ores. PMID- 20287884 TI - The action of elementary fluorine upon organic compounds. PMID- 20287888 TI - Automatic filtration system. PMID- 20287889 TI - Supply of hot water at constant temperature. PMID- 20287890 TI - Siphoning; a safe and simple way. PMID- 20287891 TI - Recrystallization of small amounts of material. PMID- 20287892 TI - Infra-red absorption spectra of steroids; progesterone and pregnane derivatives. PMID- 20287893 TI - Studies on the mercapturic acid synthesis in animals; on the mechanism of inhibition of growth of rats by benzyl chloride. PMID- 20287894 TI - The growth-promoting activity of cholesterol and related compounds in black carpet beetle larvae. PMID- 20287895 TI - Decrease of phosphocreatine in regenerating neurons. PMID- 20287896 TI - Succinic dehydrogenase in regenerating neurons. PMID- 20287897 TI - The state of vitamin A in colostrum and in milk. PMID- 20287898 TI - The isolation and properties of the proteins associated with tetanus antitoxic activity in equine plasma. PMID- 20287899 TI - Dihydroxyphenylalanine metabolism in the presence of kidney and liver slices of normal and scorbutic guinea pigs. PMID- 20287900 TI - The synthesis of benzyl-(3)-thiazolium chloride analogues of thiamine. PMID- 20287901 TI - Studies of actin and myosin. PMID- 20287902 TI - On the Graff modification of the Vickery-White procedure for the estimation of cystine. PMID- 20287903 TI - The determination of guanidoacetic acid and arginine in human urine and serum. PMID- 20287904 TI - The metabolism of nicotinic acid and its role in the nutrition of the calf. PMID- 20287905 TI - Folic acid activity of N-(4-(4-quinazoline)-benzoyl)glutamic acid. PMID- 20287906 TI - Effect of cyanide on the concentration of lactate and phosphates in brain. PMID- 20287907 TI - Effect of convulsive activity upon the concentration of brain glucose, glycogen, lactate, and phosphates. PMID- 20287908 TI - The determination of plasma or serum albumin by means of a precipitin reaction. PMID- 20287909 TI - Comparative properties of purified preparations of two distinctive strains of tobacco mosaic virus obtained from diseased Turkish tobacco and phlox plants. PMID- 20287910 TI - The composition of the cholesterol esters and glycerides in the liver of the rat. PMID- 20287911 TI - Spectrophotometric studies of the Roe method for the determination of dehydroascorbic acid. PMID- 20287912 TI - On the activation of molecular hydrogen by Proteus vulgaris. PMID- 20287913 TI - The hydrogenation of fumarate by heavy hydrogen in the presence of Bacillus coli. PMID- 20287914 TI - Diacetyl mutase. PMID- 20287915 TI - Pyruvic and alpha-ketoglutaric oxidase of animal tissue. PMID- 20287917 TI - Further studies on the amino acid composition of seed globulins. PMID- 20287916 TI - The action of phenylmercuric nitrate; inability of sulfhydryl compounds to reverse the depression of cytochrome oxidase and yeast respiration caused by basic phenylmercuric nitrate. PMID- 20287918 TI - Spectrophotometric measurement of hexokinase and phosphohexokinase activity. PMID- 20287919 TI - Free and combined glutamic acid in human blood plasma and serum. PMID- 20287920 TI - Comparative distribution of a stimulatory factor for Streptococcus faecalis R and the monkey antianemia factor. PMID- 20287921 TI - Coenzyme for acetylation, a pantothenic acid derivative. PMID- 20287922 TI - Reversible oxidative decarboxylation of malic acid. PMID- 20287923 TI - Substances in human saliva from non-secretors. PMID- 20287924 TI - On the utilization of glycine for uric acid synthesis in man. PMID- 20287926 TI - Growth of Clostridium welchii (BP6K). PMID- 20287925 TI - The inactivation of pteroylglutamic acid (liver Lactobacillus casei factor) by light. PMID- 20287927 TI - Desamidation of amides in the presence of pyruvate furnished by concomitant reactions. PMID- 20287928 TI - Maxillo-facial and other prostheses. PMID- 20287929 TI - Pyorrhoea based on an understanding of its aetiology. PMID- 20287930 TI - The New Zealand School Dental Service. PMID- 20287931 TI - Fracture of the styloid process. PMID- 20287932 TI - Nitrous oxide anaesthesia. PMID- 20287933 TI - The extraction of teeth, deciduous and permanent, in the causation and treatment of malocclusion. PMID- 20287934 TI - The principles and technique of plastic-gold bridgework. PMID- 20287935 TI - Osteoclastoma over an unerupted tooth. PMID- 20287936 TI - Bilateral cleft lips. PMID- 20287937 TI - An unusual fixed bridge problem. PMID- 20287938 TI - Technique of local anesthesia for children. PMID- 20287939 TI - Interchangeable acrylic teeth. PMID- 20287941 TI - Use of penicillin in dentistry. PMID- 20287940 TI - Chronic enlargement of the maxilla and mandible. PMID- 20287942 TI - Restorations with amalgam in the Army; an evaluation and analysis. PMID- 20287943 TI - Importance of the mercury-alloy ratio to the amalgam filling. PMID- 20287944 TI - The use of penicillin in treatment of the root canal. PMID- 20287945 TI - Penicillin in the treatment of Vincent's infection. PMID- 20287946 TI - Internal resorption of teeth; interpretation of histologic findings. PMID- 20287947 TI - A cause of delayed hemorrhage after tooth extraction. PMID- 20287948 TI - STATEMENT on control of dental caries. PMID- 20287949 TI - Experimental investigation of the referred pain of aerodontalgia. PMID- 20287950 TI - Some observations on the clearance of glucose from the oral cavity. PMID- 20287951 TI - Studies of changes in pH produced by pure cultures of oral micro-organisms; effects of varying the microbic cell concentration; comparison of different micro organisms and different substrates; some effects of mixing certain micro organisms. PMID- 20287952 TI - A method for the chemical measurement of activity of caries of the enamel. PMID- 20287953 TI - Carious lesions in cotton rat molars; the role of mechanical factors studied by the extraction of antagonistic molars. PMID- 20287954 TI - The illusory sheath of Neumann in dentin. PMID- 20287955 TI - Chemical studies in periodontal disease; putrefaction rate as index of periodontal disease. PMID- 20287957 TI - Chemical changes in the dentin following ageing and peripheral irritation. PMID- 20287956 TI - Development of rat molar crowns and jaws. PMID- 20287959 TI - The use of acrylic resins in restorative dentistry. PMID- 20287958 TI - A comparative study of the effects of glycerite of hydrogen peroxide and of hexylresorcinol on the bacteria of the normal mouth. PMID- 20287960 TI - Application of mucostatic principles to full denture construction. PMID- 20287961 TI - Clinical use of a new antihistaminic compound (pyribenzamine) in certain cutaneous disorders. PMID- 20287963 TI - Kaposi's varicelliform eruption. PMID- 20287962 TI - Dermatologic problems in a staging area station hospital. PMID- 20287964 TI - Dermatophytosis of the face caused by Trichophyton camerounense. PMID- 20287965 TI - Granuloma inguinale involving buttock and lymph node; cultivation of the Donovan body in embryonic yolk. PMID- 20287966 TI - Acne vulgaris treated with vitamin A. PMID- 20287967 TI - Leishmaniasis verrucosa of the face. PMID- 20287968 TI - Cutaneous diphtheria and tropical ulcers. PMID- 20287969 TI - Epidermolysis bullosa of the newborn. PMID- 20287970 TI - Basal cell epithelioma in a psoriatic patch. PMID- 20287971 TI - Treatment of mycotic infections by inhibiting respiration of dermatophytes. PMID- 20287972 TI - Reactions in the treatment of syphilis with penicillin. PMID- 20287974 TI - Use of the purple X bulb in diagnosis of fungous diseases of the scalp. PMID- 20287973 TI - Undecylenic and propionic acids in the prevention and treatment of dermatophytosis. PMID- 20287976 TI - Xanthoma disseminatum (also tuberosum et planum). PMID- 20287975 TI - Possible benefit from protein hydrolysates for exfoliative dermatitis. PMID- 20287977 TI - Xanthoma disseminatum. PMID- 20287978 TI - A case for diagnosis (syphilitic glossitis?). PMID- 20287979 TI - A case for diagnosis (tuberculosis orificialis?). PMID- 20287980 TI - A case for diagnosis (multiple idiopathic hemorrhagic sarcoma or hemangioendothelioblastoma?). PMID- 20287981 TI - Juvenileacanthosis nigricans and ichthyosis. PMID- 20287982 TI - A case for diagnosis (psoriasis; dermatitis medicamentosa?). PMID- 20287983 TI - Tertiary syphilis of the skin. PMID- 20287984 TI - A case for diagnosis (dermatitis medicamentosa?). PMID- 20287985 TI - A case for diagnosis (dermatitis herpetiformis or pemphigus?). PMID- 20287986 TI - Dermatitis venenata. PMID- 20287987 TI - A case for diagnosis (Bowen's disease? tuberculosis cutis?). PMID- 20287988 TI - Hydroa vacciniforme (hydroa aestivale). PMID- 20287989 TI - Syringocystadenoma. PMID- 20287990 TI - Sarcoidosis. PMID- 20287991 TI - Tinea barbae. PMID- 20287992 TI - Prurigo nodularis. PMID- 20287993 TI - Pseudopelade. PMID- 20287994 TI - Generalized vitiligo; alopecia of undetermined cause. PMID- 20287995 TI - Multiple keloids in twin sisters. PMID- 20287996 TI - Necrobiosis lipoidica diabeticorum. PMID- 20287997 TI - Necrobiosis lipoidica diabeticorum. PMID- 20287998 TI - Leukoderma acquisitum centrifugum. PMID- 20287999 TI - Perforating ulcer of the foot in two sisters. PMID- 20288000 TI - Large, otherwise normal gastric rugae simulating tumor of the stomach; a report of three cases. PMID- 20288001 TI - Criteria for gastroscopic examination in the Army. PMID- 20288002 TI - Amebiasis; observations in an Army general hospital in India. PMID- 20288003 TI - Observations on the methylene blue test for bile pigment in urine. PMID- 20288004 TI - Organization of the gastrointestinal service in the Army during the second World War; personal observations and impressions. PMID- 20288005 TI - Gastric surgery; a review of the literature for 1945. PMID- 20288006 TI - Clinical and pathological findings in prolonged hepatitis. PMID- 20288007 TI - Laennec's cirrhosis; the effect of therapy in increasing life expectancy. PMID- 20288008 TI - Anion exchange resin and peptic ulcer pain. PMID- 20288009 TI - A polyamine formaldehyde resin; chronic toxicity experiment in rats. PMID- 20288010 TI - The treatment of peptic ulcer with anion exchange resins. PMID- 20288011 TI - Report of a preliminary clinical trial of dibutoline, a new antispasmotic drug. PMID- 20288012 TI - The effect of cigarette smoking on malnutrition and digestion. PMID- 20288013 TI - Interesting X-ray findings in a case of acute fulminating ulcerative colitis. PMID- 20288014 TI - Sprue as a sequel to the war's migration of military personnel. PMID- 20288015 TI - ACHES and pains and sorenesses due to psychogenic rheumatism. PMID- 20288016 TI - Psychosomatic gastrointestinal problems in the United States Army. PMID- 20288017 TI - The effect of testosterone propionate on carcinoma of the female breast with soft tissue metastases. PMID- 20288018 TI - Craniopharyngioma with panhypopituitarism; case report with clinical and pathological study. PMID- 20288019 TI - Bilateral cryptorchism in identical twins. PMID- 20288020 TI - Chronic cystic mastitis and sterility. PMID- 20288021 TI - The use of methyl testosterone in the treatment of premature infants. PMID- 20288022 TI - Gastric dysfunction of hypoestrogenic origin; treatment with benzestrol. PMID- 20288023 TI - Androgenic arrest of familial enuresis in 75 children. PMID- 20288024 TI - The advance of American medicine. PMID- 20288025 TI - Pregnancy in the patient with hypertensive disease. PMID- 20288026 TI - Morbidity associated with induction of labor. PMID- 20288027 TI - The treatment of pelvic tuberculosis in the female by radiation therapy based upon experimental evidence in the animal and clinical results in the human. PMID- 20288028 TI - The background of cancer of the corpus. PMID- 20288029 TI - Pituitary extract in uterine inertia; is it justifiable? PMID- 20288030 TI - An analysis of deaths from postpartum hemorrhage. PMID- 20288031 TI - The treatment of amenorrhea in young women. PMID- 20288032 TI - Serology and obstetrics. PMID- 20288033 TI - The Rh factor in abortion. PMID- 20288034 TI - Red degeneration of uterine myomas. PMID- 20288035 TI - Conservative treatment and therapeutic test for endometriosis by androgens. PMID- 20288036 TI - The second stage of labor; internal rotation. PMID- 20288037 TI - The obstetric management of pregnancy complicated by heart disease. PMID- 20288038 TI - The problem of talcum glove powder and contraindications for its employment. PMID- 20288039 TI - A discussion of classification of toxemias of pregnancy. PMID- 20288040 TI - A preliminary evaluation of dienestrol in the menopause. PMID- 20288041 TI - Dysgerminoma of the ovary. PMID- 20288042 TI - Adrenal-like masculinizing tumor of the ovary associated with bleeding fibromyoma uteri. PMID- 20288043 TI - Absorption of penicillin from the vagina. PMID- 20288044 TI - Vaginal lacerations resulting from coitus. PMID- 20288045 TI - [Not Available]. PMID- 20288046 TI - [Not Available]. PMID- 20288047 TI - [Not Available]. PMID- 20288048 TI - [Not Available]. PMID- 20288049 TI - [Not Available]. PMID- 20288050 TI - [Not Available]. PMID- 20288051 TI - Dietary factors concerned in erythropoiesis. PMID- 20288052 TI - The effect of diet on the hemoglobin, erythrocyte, and leukocyte content of the blood of the rhesus monkey (Macaca mulatta). PMID- 20288053 TI - Hemopoiesis in riboflavin-deficient rats. PMID- 20288054 TI - The hematologic response in dogs to the administration of anti spleen serum. PMID- 20288055 TI - Contribution to the pathogenesis of hemophilia. PMID- 20288056 TI - Renal function during chronic anemia in man. PMID- 20288057 TI - Symposium; procedures in structural diagnosis. PMID- 20288059 TI - Procedures in structural diagnosis; special methods in structural diagnosis. PMID- 20288058 TI - Procedures in structural diagnosis; soft tissues in areas of osteopathic lesion. PMID- 20288060 TI - Experiences with early rising after surgical operation. PMID- 20288061 TI - Direct writing electrocardiography. PMID- 20288062 TI - Therapeutics of the nephritides. PMID- 20288063 TI - Streptomycin. PMID- 20288064 TI - Clinical classification of pulmonary tuberculosis. PMID- 20288065 TI - Prostigmine. PMID- 20288066 TI - Allergy; diagnostic considerations. PMID- 20288067 TI - An evaluation of surgery in carcinoma of the lung. PMID- 20288068 TI - A foot cast platform and plantar impression viewer. PMID- 20288069 TI - Chiropody University Affiliation Endowment Society organized. PMID- 20288070 TI - Unilateral congenital metatarsal synostosis; a case report. PMID- 20288071 TI - The patch test in contact dermatitis. PMID- 20288072 TI - Kuvor; its uses and application in podiatry practice. PMID- 20288073 TI - Problems of the tuberculous veteran. PMID- 20288074 TI - Podopediatrics. PMID- 20288075 TI - The care of soldiers' feet. PMID- 20288076 TI - Electroshock therapy in osteopathic psychiatric practice. PMID- 20288077 TI - Infant feeding. PMID- 20288078 TI - Plastics in hospital equipment. PMID- 20288079 TI - Plans and prospects for hospital standardization in 1947. PMID- 20288081 TI - Plans for graduate training in surgery in 1947. PMID- 20288080 TI - The nursing problem. PMID- 20288082 TI - Post-war student nurse recruitment problems. PMID- 20288083 TI - The training of a secondary group for nursing service. PMID- 20288084 TI - Summary of the report and of the conclusions and recommendations of the Commission on Hospital Care. PMID- 20288085 TI - Program of the American Association of Medical Record Librarians to improve medical record science. PMID- 20288086 TI - The importance of complete and scientific medical records from the standpoint of better care of the patient. PMID- 20288087 TI - The importance of complete and scientific medical records from the standpoint of self education of the practicing physician. PMID- 20288088 TI - Education and training of interns and residents; the written word tells the story. PMID- 20288090 TI - The governing board of the hospital. PMID- 20288089 TI - The importance of complete and scientific medical records from the standpoint of advancement of medical science. PMID- 20288091 TI - The education of the hospital trustee. PMID- 20288092 TI - Minimum qualifications to practice major surgery. PMID- 20288093 TI - Co-operation between Blue Cross and medical service plans and hospitals. PMID- 20288094 TI - Development of training for surgery. PMID- 20288095 TI - Transportation of the injured and other types of emergency patients; ambulance service. PMID- 20288096 TI - Emergency ambulance service. PMID- 20288097 TI - Ante- and post-partum hemorrhage. PMID- 20288099 TI - PSYCHIATRIC nursing; a career that is worth while. PMID- 20288098 TI - Emergencies arising during anesthesia. PMID- 20288100 TI - Place of social worker in National Health Service. PMID- 20288101 TI - Hospital ventilation; some important points for consideration. PMID- 20288102 TI - Labor Health Institute pioneers in low cost medical care for workers. PMID- 20288103 TI - Philadelphia Psychiatric Hospital points the way in design and treatment. PMID- 20288104 TI - A surgeon analyzes nurse shortage and makes some suggestions. PMID- 20288105 TI - The effect of heat upon antihemocyanin. PMID- 20288106 TI - Studies on the nature of antibodies produced in vitro from bacteria with hydrogen peroxide and heat. PMID- 20288107 TI - Immunization of humans and animals with gas gangrene toxoids. PMID- 20288108 TI - Studies on botulinum toxoid, types A and P; production of alum precipitated toxoids. PMID- 20288109 TI - Studies on botulinum toxoid, types A and B; methods for determining antigenicity in animals. PMID- 20288110 TI - A comparative study of pathogenicity and antigenicity of four strains of herpes simplex. PMID- 20288111 TI - The clinical behavior, incubation period, and pathology of tetanus induced in white Swiss mice by injection of crystalline tetanal toxin. PMID- 20288112 TI - Size and morphology of the elementary bodies of the psittacosis-lymphogranuloma group of viruses. PMID- 20288113 TI - Effect of tris(beta-chloroethyl)amine on antibody production in goats. PMID- 20288114 TI - Immunological relationship of mammary carcinomas developing spontaneously in female mice of a high-tumor line. PMID- 20288115 TI - Incompatability of mother and foetus with respect to the iso-agglutinogen A and its antibody. PMID- 20288116 TI - A documentary study of jaundice associated with syphilis treatment and blood transfusion. PMID- 20288117 TI - Epidemiology of infective hepatitis among Allied troops in Italy. PMID- 20288118 TI - A study of the haematology of 663 substandard recruits under training at an army physical development centre. PMID- 20288119 TI - The role of the industrial physician in the personnel department. PMID- 20288120 TI - An evaluation of some factors in the development of occupational deafness. PMID- 20288121 TI - False aneurysm. PMID- 20288122 TI - New methods in the treatment of tuberculosis. PMID- 20288123 TI - Neuropsychiatric conditions in railroad employees. PMID- 20288124 TI - Persistent hematoma; case report. PMID- 20288125 TI - Treatment of infected war wounds with a nitrofuran. PMID- 20288127 TI - Industry's toothache. PMID- 20288126 TI - The diagnosis and treatment of spinal cord injuries. PMID- 20288128 TI - The carious tooth as a portal of entry for poliomyelitis. PMID- 20288129 TI - Medicolegal aspects of industrial medicine. PMID- 20288130 TI - Artists and their work. PMID- 20288131 TI - An experimental study of the relationship between certainty of choice and the relative valence of alternatives. PMID- 20288132 TI - Identification with the enemy; a case study of an American Quisling. PMID- 20288133 TI - A contribution of a medieval Arab scholar to the problem of learning. PMID- 20288134 TI - Thematic apperception tests; suggestions for administration and interpretation. PMID- 20288135 TI - Symposium on working capacity. PMID- 20288137 TI - Industrial pulmonary diseases and capacity for work. PMID- 20288136 TI - Nutrition and capacity for work. PMID- 20288138 TI - Heart disease and working capacity in industry. PMID- 20288139 TI - Medical treatments in Gulf Coast shipyards. PMID- 20288140 TI - Symposium on fitness for work. PMID- 20288141 TI - Need for a campaign for physical fitness. PMID- 20288142 TI - Does American education produce physically fit workers? PMID- 20288143 TI - Evaluation of fitness. PMID- 20288144 TI - Psychosomatic elements; when the foreman is a pain in the neck. PMID- 20288145 TI - Conserving the health of management. PMID- 20288146 TI - The effect of B-complex vitamins on the voluntary consumption of alcohol by rats. PMID- 20288147 TI - Insulin subshock as a detoxicant in acute alcoholic intoxication. PMID- 20288148 TI - Imprisoned abnormal drinkers; application of the Bowman-Jellinek classification schedule to an institutional sample; review and analysis of data. PMID- 20288149 TI - The etiology of alcoholism; a working hypothesis involving the interplay of hereditary and environmental factors. PMID- 20288150 TI - Contribution of alcohol to accident fatalities in Hennepin County during a one year period. PMID- 20288151 TI - An opinion poll on reactions to The Lost Weekend. PMID- 20288152 TI - Studies on malignant hepatitis. PMID- 20288153 TI - Diagnosis of acute respiratory tract infections. PMID- 20288154 TI - The changing concept of myeloma of bone. PMID- 20288155 TI - Disseminated calcification of the pancreas; subacute and chronic pancreatitis. PMID- 20288156 TI - Experiences with penicillin and dicumarol in the treatment of subacute bacterial endocarditis. PMID- 20288157 TI - The treatment of acute diphtheria and the chronic carrier state with penicillin. PMID- 20288158 TI - The effects of blockade of the autonomic ganglia in man with tetraethylammonium; preliminary observations on its clinical application. PMID- 20288159 TI - Insensitivity to epinephrine in a patient with a functioning tumor of the adrenal medulla. PMID- 20288160 TI - Increased reactivity caused by adrenalin. PMID- 20288161 TI - Thiamine circulation time. PMID- 20288162 TI - The electrocardiographic changes caused by hyperventilation. PMID- 20288163 TI - Injectional treatment of internal hemorrhoids. PMID- 20288164 TI - Complications of mumps. PMID- 20288165 TI - Further report on the use of bismuth sodium tartrate intravenously in the treatment of 203 additional patients with tularemia. PMID- 20288166 TI - Flea versus rat control in human plague. PMID- 20288167 TI - Light and dark adaptation of single visual sense cells. PMID- 20288168 TI - Kidney phosphatase in alimentary hyperglycemia and phlorhizin glycosuria; a dynamic mechanism for renal threshold for glucose. PMID- 20288169 TI - The separation of blood into fractions of therapeutic value. PMID- 20288170 TI - The use of gamma globulin from large pools of adult blood plasma in certain infectious diseases. PMID- 20288171 TI - Hemophilia; the clinical use of antihemophilic globulin. PMID- 20288172 TI - Other uses of plasma fractions with particular reference to serum albumin. PMID- 20288173 TI - Bronchiogenic carcinoma; an analysis of 343 cases. PMID- 20288174 TI - Rehabilitation; wartime lessons applied to peacetime needs. PMID- 20288175 TI - Penicillin in the treatment of neurosyphilis; cerebrospinal fluid changes in symptomatic neurosyphilis. PMID- 20288176 TI - The management of infectious hepatitis. PMID- 20288177 TI - Reflex sympathetic dystrophy; report on 57 cases. PMID- 20288178 TI - Spondylosis and spondylarthritis. PMID- 20288179 TI - Malignant thymoma in a case of myasthenia gravis. PMID- 20288180 TI - Primary amyloidosis; report of a case. PMID- 20288181 TI - Palindromic rheumatism. PMID- 20288182 TI - PSEUDOHEMOPHILIA. PMID- 20288183 TI - Artificial limbs. PMID- 20288184 TI - Medical relief in famine areas. PMID- 20288185 TI - Flatfoot. PMID- 20288186 TI - Perforation of hard palate by maggots. PMID- 20288187 TI - A case of miliary tuberculosis. PMID- 20288188 TI - Psycho-therapy in neurotic cases. PMID- 20288189 TI - A new cure for opium poisoning. PMID- 20288190 TI - An interesting case of malingering. PMID- 20288191 TI - Hyperchromic anaemias. PMID- 20288192 TI - A modified E. M. S. hospital for emergency work in Austria. PMID- 20288193 TI - 50 years of X-rays. PMID- 20288194 TI - The treatment of goitres; a new therapeutic approach. PMID- 20288195 TI - Plant hormones; substances which control plant growth. PMID- 20288196 TI - Night-nurse's paralysis; a temporary tonic motor paralysis. PMID- 20288197 TI - Campaigning notes, 1940-45. PMID- 20288198 TI - Influence of nephrectomy upon hypertension in forty-nine patients with demonstrable unilateral renal disease. PMID- 20288199 TI - Recovery from influenzal meningitis following treatment with streptomycin. PMID- 20288200 TI - Disruption of abdominal wounds; a study of 27 cases. PMID- 20288201 TI - Early ambulation in obstetrics. PMID- 20288202 TI - Demerol for analgesia in obstetrics. PMID- 20288203 TI - Rh incompatibility as a factor in the delayed healing of surgical wounds. PMID- 20288204 TI - [Lupus erythematosus disseminatus]. PMID- 20288205 TI - The clinical significance of hemoptysis; an analysis of 1316 personal cases. PMID- 20288206 TI - Physiological studies in congenital heart disease. PMID- 20288207 TI - Physiological studies in congenital heart disease; results of preoperative studies in patients with tetralogy of Fallot. PMID- 20288208 TI - The lipotropic effect of N1-methyl nicotinamide. PMID- 20288213 TI - A new approach to the treatment of typhoid fever. PMID- 20288214 TI - Some observations on medical evidence in courts. PMID- 20288215 TI - Diagnostic roentgenology in obstetrics. PMID- 20288216 TI - A new treatment of osteo-arthritis. PMID- 20288217 TI - Deficiency anemias. PMID- 20288218 TI - Diethyl oxide; new therapy in impending gangrene. PMID- 20288219 TI - Control of bleeding during cholecystectomy. PMID- 20288220 TI - The young doctor; the technic of entering practice. PMID- 20288221 TI - Idiopathic thrombophlebitis. PMID- 20288222 TI - Phlyctenular conjunctivitis; a clinical and radiological study of 28 cases. PMID- 20288223 TI - Breast feeding as a clinical and social problem. PMID- 20288224 TI - Yaws. PMID- 20288225 TI - The blood sedimentation rate in South African native mental patients; an investigation of a series of 200 cases using the Westergren method. PMID- 20288226 TI - A case of dystrophia myotonia. PMID- 20288227 TI - Relationships between disease of the coronary arteries and the alimentary tract. PMID- 20288228 TI - A systematic approach to aetiology in medicine. PMID- 20288229 TI - Recent trends in the treatment of megaloblastic anaemias. PMID- 20288230 TI - Estimation of haemoglobin by the copper sulphate gravimetric method. PMID- 20288231 TI - Obesity. PMID- 20288232 TI - Improper management of psychosomatic syndromes; diagnosed and treated as true organic disease. PMID- 20288233 TI - Fundamental principles of skin grafting. PMID- 20288234 TI - Treatment of diarrhea in infants. PMID- 20288235 TI - Ion-transfer therapy. PMID- 20288236 TI - Vitamin C. PMID- 20288237 TI - The treatment of rheumatoid arthritis via vasodilatation. PMID- 20288238 TI - Value of a history in the differential diagnosis of jaundice. PMID- 20288239 TI - Treatment of subacute bacterial endocarditis with penicillin. PMID- 20288240 TI - Graduate training in psychiatry. PMID- 20288241 TI - Clinical signs and symptoms of vitamin deficiencies. PMID- 20288242 TI - The work of the Maternal Welfare Committee. PMID- 20288243 TI - Spa therapy. PMID- 20288244 TI - Interneships in China. PMID- 20288245 TI - Some observations on dietary levels in the population. PMID- 20288246 TI - Ovarian tumors. PMID- 20288247 TI - Trends in the care of the psychiatric case. PMID- 20288248 TI - The gonadotrophic hormones. PMID- 20288249 TI - Ketosis; diabetic coma and its treatment. PMID- 20288250 TI - On adult mental age. PMID- 20288251 TI - Ketosis; diabetic coma and its treatment. PMID- 20288252 TI - Ovarian tumors. PMID- 20288253 TI - Adequate medical care. PMID- 20288254 TI - Rickettsialpox; a newly recognized rickettsial disease; clinical observations. PMID- 20288255 TI - Prophylactic chemotherapy in appendicitis; preliminary report of one hundred and eight cases. PMID- 20288256 TI - Chronic subclinical impairment of the liver; early diagnosis and treatment; further improvement and evaluation of certain liver function tests. PMID- 20288257 TI - The healing open pilonidal wound; unique characteristics and clinical implications. PMID- 20288258 TI - Cancer of the cervix; a local recurrence eighteen years after radium therapy. PMID- 20288259 TI - JOINT committee for the Coordination of Medical Activities; Chicago, Jan. 11, 1947. PMID- 20288260 TI - Psychiatric sense and nonsense. PMID- 20288261 TI - Rheumatic fever; its recognition and treatment. PMID- 20288262 TI - Atypical features of rheumatic fever in young adults. PMID- 20288263 TI - Para-aminobenzoic acid therapy of Rocky Mountain spotted fever; outline of a comprehensive plan of treatment with report of five cases. PMID- 20288264 TI - Intestinal tumors of dysenteric origin. PMID- 20288265 TI - Chronic ulcerative colitis; proctologic interpretation and treatment. PMID- 20288266 TI - False positive tests for syphilis; a study of their incidence in sporozoite induced vivax malaria. PMID- 20288267 TI - Pilonidal disease; present status of management. PMID- 20288268 TI - Tetany following mercurial diuresis. PMID- 20288270 TI - Studies on healthy bone marrow from sternal puncture. PMID- 20288269 TI - Medical service areas in the United States. PMID- 20288271 TI - Intestinal helminthiasis. PMID- 20288273 TI - Typhoid fever in children. PMID- 20288272 TI - Glucose treatment of diabetes and effect of sedatives with a case report. PMID- 20288274 TI - Poverty and nutrition. PMID- 20288275 TI - Need of scientific medicine in India. PMID- 20288276 TI - The use of drugs in acute myocardial infarction. PMID- 20288277 TI - Surgical treatment of deafness. PMID- 20288278 TI - A summary of cancerology; diagnoses. PMID- 20288279 TI - The story of a district hospital. PMID- 20288281 TI - A summary of cancerology; treatment. PMID- 20288280 TI - The interpretation of blood count findings. PMID- 20288282 TI - Treatment of H. influenzae meningitis. PMID- 20288283 TI - Results from the treatment of peptic ulcer. PMID- 20288284 TI - Acute glomerulonephritis. PMID- 20288285 TI - Dermatitis medicamentosa. PMID- 20288286 TI - Psychosomatic study of a case of gynecomastia. PMID- 20288287 TI - Coloboma of optic nerve. PMID- 20288288 TI - Vitamins in the urine of newborn infants. PMID- 20288289 TI - Antibiotic agents and some general principles of antibiotic therapy. PMID- 20288290 TI - Parasitic infections in West Africa. PMID- 20288291 TI - Cancer of the gastrointestinal tract. PMID- 20288292 TI - Fevers of undetermined origin. PMID- 20288293 TI - The hospital as a humanitarian institution; with special reference to the Negro hospital. PMID- 20288294 TI - The diagnosis and treatment of cardiac emergencies. PMID- 20288295 TI - Sulfonamide anuria. PMID- 20288296 TI - Brucellosis in children. PMID- 20288297 TI - Gastric resection for carcinoma of stomach; Kronlein technique. PMID- 20288298 TI - Mono-amniotic twins; danger to the life of at least one twin. PMID- 20288299 TI - Radiological finding in syphilis of the rectum. PMID- 20288300 TI - Sixty-two consecutive cases of symphyseotomy. PMID- 20288301 TI - Recent experiences with transurethral urological surgery. PMID- 20288302 TI - Proposed principles of medical ethics of the medical profession in the Philippines. PMID- 20288303 TI - Still-births and neonatal deaths in the Philippine General Hospital after liberation (April 5, 1945 to April 4, 1946). PMID- 20288304 TI - The adequacy of postwar diet of Filipino wage earners in the City of Manila. PMID- 20288306 TI - Some newer knowledge in parasitology; a review. PMID- 20288305 TI - Tetrachlorethylene treatment of ankylostomiasis. PMID- 20288307 TI - Modern chemistry applied to modern medicine. PMID- 20288308 TI - A striking response with thiouracil in hyperthyroidism. PMID- 20288309 TI - Paracelsus (1493-1541) the iconoclast; a Renaissance doctor. PMID- 20288310 TI - Atomic energy. PMID- 20288311 TI - Added infections in burns; a study of 233 cases. PMID- 20288312 TI - Hypertensive headache treated with potassium thiocyanate. PMID- 20288313 TI - Stevens-Johnson syndrome; report of a case. PMID- 20288314 TI - Stevens-Johnson syndrome; report of two cases. PMID- 20288315 TI - Urinary excretion of phosphatases in man. PMID- 20288316 TI - The interpretation of blood-sugar levels in children. PMID- 20288317 TI - The intravenous drip. PMID- 20288318 TI - Foetal death and eclampsia. PMID- 20288319 TI - PSYCHOSOMATIC approach to orthopaedic surgery. PMID- 20288320 TI - Amyloid macroglossia. PMID- 20288321 TI - Stammering. PMID- 20288322 TI - Non-dysenteric amebiasis; general considerations and possible relationship to rheumatoid arthritis. PMID- 20288323 TI - Late manifestations of tropical diseases. PMID- 20288324 TI - The National Hotel epidemic of 1857. PMID- 20288325 TI - Glomus tumor. PMID- 20288326 TI - Neurological surgery in Washington. PMID- 20288327 TI - PROPOSED uniform state barbiturate act; an act to regulate the handling, sale and distribution of barbiturates. PMID- 20288328 TI - The Washington Institute of Mental Higiene; its origin and function. PMID- 20288329 TI - The indurated leg; a consideration of its causes and treatment. PMID- 20288330 TI - Intrarenal lipoma; with report of an unusual case. PMID- 20288331 TI - Intracerebral pneumatocele; report of a case. PMID- 20288332 TI - The evaluation of shock in surgical and anaesthetic procedures. PMID- 20288333 TI - Acute frontal sinusitis with intra-cranial complication. PMID- 20288335 TI - Medical care. PMID- 20288334 TI - Tuberculosis and cancer of the lung; errors in diagnosis. PMID- 20288336 TI - Toxic agents in the genesis of pellagra and pellagroid. PMID- 20288337 TI - Vitamin E in heart disease; the anginal syndrome. PMID- 20288338 TI - Vitamin K in spinal anesthesia with procaine. PMID- 20288339 TI - Surgery of thyrotoxic goiter. PMID- 20288340 TI - Evaluation of a new hypotensive formula. PMID- 20288341 TI - FIGHT against the antivivisectionists. PMID- 20288342 TI - Minerals in nutrition. PMID- 20288343 TI - Progress during psychoanalytical treatment. PMID- 20288344 TI - The dietary management of diabetes. PMID- 20288345 TI - Progress in the treatment of heart diseases; a review of the literature. PMID- 20288346 TI - Observation and interpretation versus a multitude of tests. PMID- 20288347 TI - Vitamin E in heart disease; the rheumatic heart. PMID- 20288348 TI - Multiple sclerosis and ecstasy. PMID- 20288349 TI - Preventive medical centers. PMID- 20288350 TI - Food plans for good nutrition. PMID- 20288351 TI - [Not Available]. PMID- 20288352 TI - Adjusting a private agency to an official program. PMID- 20288353 TI - Red cross activities in poliomyelitis. PMID- 20288354 TI - Pathology of puberty. PMID- 20288355 TI - [Not Available]. PMID- 20288356 TI - The diagnosis and treatment of some common acute surgical diseases of the anal canal. PMID- 20288357 TI - The Monros of Edinburgh; Alexander Monro Primus; the origin of the medical school. PMID- 20288358 TI - Diagnosis and management of gall bladder disease. PMID- 20288359 TI - Treatment of sacroiliac sprain by manipulation. PMID- 20288360 TI - The treatment of prostatism. PMID- 20288361 TI - What is the treatment of congestive heart failure? PMID- 20288362 TI - Look with suspicion at rectal irregularities; medicine's step-child, cancer of the rectum. PMID- 20288363 TI - Use of iodolake in the treatment of upper respiratory tract. PMID- 20288364 TI - Surgery of the thyroid gland. PMID- 20288365 TI - Visceral leishmaniasis; report of a case. PMID- 20288366 TI - Co-existent primary carcinoma of the fallopian tube and of the breast. PMID- 20288367 TI - Complete absence of lochia following delivery; report of a case. PMID- 20288368 TI - The physiologic and clinical significance of plasma proteins and protein metabolites. PMID- 20288369 TI - Ulcerative colitis. PMID- 20288370 TI - [Chronic glomerulonephritis, inactive]. PMID- 20288372 TI - MEANING of psychosomatic medicine. PMID- 20288371 TI - NEW rickettsial infection in New York City. PMID- 20288373 TI - Treatment of injuries to the knee joint. PMID- 20288374 TI - Results of bilateral supradiaphragmatic splanchnicectomy for arterial hypertension. PMID- 20288375 TI - Penicillin in the treatment of gonorrhea in women; results of treatment as reported by twelve cooperating venereal disease clinics in Massachusetts during 1945. PMID- 20288376 TI - Syphilis. PMID- 20288377 TI - [Brain tumor, probably oligodendroglioma]. PMID- 20288378 TI - [Acute sinusitis, left ethmoid and sphenoid]. PMID- 20288379 TI - Psychosomatic medicine. PMID- 20288380 TI - Military surgery in World War II; a backward glance and a forward look. PMID- 20288381 TI - Protein nutrition; the therapeutic use of a digest of liver protein, especially in patients with cirrhosis of the liver. PMID- 20288382 TI - Congenital dislocation of the knee; report of a case. PMID- 20288383 TI - Synthetic plastic materials in surgery. PMID- 20288384 TI - [Subdiaphragmatic and subhepatic abscess, secondary to cholecystectomy]. PMID- 20288385 TI - [Chronic pancreatitis, with extension to wall of stomach]. PMID- 20288386 TI - Arthritis in the Mediterranean Theater of Operations; incidence of joint disease; clinical description of rheumatoid arthritis. PMID- 20288388 TI - Neuropathic foot lesions in diabetes mellitus. PMID- 20288387 TI - The prevention of postoperative pulmonary embolism; an analysis of fifty-two fatal cases in six years. PMID- 20288389 TI - Synthetic plastic materials in surgery. PMID- 20288390 TI - [Mesothelioma of pleura and pericardium, with metastases to right lung and retroperitoneal lymph nodes]. PMID- 20288391 TI - [Colloid carcinoma of sigmoid, with perforation and localized peritonitis]. PMID- 20288392 TI - Second-day encephalography, with particular reference to the size of the ventricles. PMID- 20288393 TI - Arthritis in the Mediterranean Theater of Operations; clinical description of hypertrophic arthritis, arthralgia and psychogenic rheumatism. PMID- 20288394 TI - Mongolism following intercurrent infectious disease in pregnancy. PMID- 20288395 TI - Pathology. PMID- 20288396 TI - [Dissecting anneurysm of aorta, with rupture into pericardium]. PMID- 20288397 TI - [Subacute bacterial endocarditis; aortic valve]. PMID- 20288398 TI - The meaning of the patient to the hospital. PMID- 20288399 TI - The voluntary hospital; how can it survive in the modern world? PMID- 20288400 TI - The possible role of the community hospital in graduate training in surgery. PMID- 20288401 TI - Arthritis in the Mediterranean Theater of Operations; clinical description of infectious and other types of arthritis. PMID- 20288402 TI - Diabetes mellitus. PMID- 20288403 TI - [Rheumatic heart disease, with severe mitral stenosis]. PMID- 20288404 TI - [Glioblastoma multiforme, right temporal lobe]. PMID- 20288405 TI - Surgical amoebiasis of the liver. PMID- 20288406 TI - Sensory disturbances in chronic visceral disease. PMID- 20288407 TI - Chemotherapy; penicillin. PMID- 20288408 TI - NEW hope for lepers; sulfa-therapy successful; no segregation necessary. PMID- 20288409 TI - Some sequels of abnormality at the thoracic outlet. PMID- 20288410 TI - The treatment of pulmonary hydatid disease. PMID- 20288411 TI - Cavernous haemangioma of the lung. PMID- 20288412 TI - [Not Available]. PMID- 20288413 TI - [Not Available]. PMID- 20288414 TI - [Not Available]. PMID- 20288416 TI - [Not Available]. PMID- 20288415 TI - [Not Available]. PMID- 20288417 TI - [Not Available]. PMID- 20288418 TI - [Not Available]. PMID- 20288419 TI - [Not Available]. PMID- 20288420 TI - [Not Available]. PMID- 20288421 TI - [Not Available]. PMID- 20288422 TI - [Not Available]. PMID- 20288423 TI - [Not Available]. PMID- 20288424 TI - [Not Available]. PMID- 20288425 TI - [Not Available]. PMID- 20288426 TI - [Not Available]. PMID- 20288427 TI - [Not Available]. PMID- 20288428 TI - [Not Available]. PMID- 20288429 TI - [Not Available]. PMID- 20288430 TI - [Not Available]. PMID- 20288431 TI - [Not Available]. PMID- 20288432 TI - [Not Available]. PMID- 20288433 TI - [Not Available]. PMID- 20288434 TI - [Not Available]. PMID- 20288435 TI - [Not Available]. PMID- 20288436 TI - [Not Available]. PMID- 20288437 TI - [Not Available]. PMID- 20288438 TI - [Not Available]. PMID- 20288439 TI - [Not Available]. PMID- 20288440 TI - [Not Available]. PMID- 20288442 TI - [Not Available]. PMID- 20288441 TI - [Not Available]. PMID- 20288443 TI - [Not Available]. PMID- 20288444 TI - [Not Available]. PMID- 20288445 TI - [Not Available]. PMID- 20288446 TI - [Not Available]. PMID- 20288447 TI - [Not Available]. PMID- 20288448 TI - [Not Available]. PMID- 20288449 TI - [Not Available]. PMID- 20288450 TI - [Not Available]. PMID- 20288451 TI - [Not Available]. PMID- 20288452 TI - [Not Available]. PMID- 20288453 TI - [Not Available]. PMID- 20288454 TI - [Not Available]. PMID- 20288455 TI - [Not Available]. PMID- 20288456 TI - [Not Available]. PMID- 20288457 TI - [Not Available]. PMID- 20288458 TI - [Not Available]. PMID- 20288459 TI - [Not Available]. PMID- 20288460 TI - [Not Available]. PMID- 20288461 TI - [Not Available]. PMID- 20288462 TI - [Not Available]. PMID- 20288463 TI - [Not Available]. PMID- 20288464 TI - [Not Available]. PMID- 20288465 TI - [Not Available]. PMID- 20288466 TI - [Not Available]. PMID- 20288467 TI - [Not Available]. PMID- 20288468 TI - [Not Available]. PMID- 20288469 TI - [Not Available]. PMID- 20288470 TI - [Not Available]. PMID- 20288471 TI - [Not Available]. PMID- 20288472 TI - [Not Available]. PMID- 20288473 TI - [Not Available]. PMID- 20288474 TI - [Not Available]. PMID- 20288476 TI - [Not Available]. PMID- 20288475 TI - [Not Available]. PMID- 20288477 TI - [Not Available]. PMID- 20288478 TI - [Not Available]. PMID- 20288479 TI - [Not Available]. PMID- 20288480 TI - [Not Available]. PMID- 20288481 TI - [Not Available]. PMID- 20288482 TI - [Not Available]. PMID- 20288483 TI - [Not Available]. PMID- 20288484 TI - [Not Available]. PMID- 20288485 TI - [Not Available]. PMID- 20288486 TI - [Not Available]. PMID- 20288487 TI - [Not Available]. PMID- 20288488 TI - [Not Available]. PMID- 20288489 TI - [Not Available]. PMID- 20288490 TI - [Not Available]. PMID- 20288491 TI - [Not Available]. PMID- 20288492 TI - [Not Available]. PMID- 20288493 TI - [Not Available]. PMID- 20288494 TI - [Not Available]. PMID- 20288496 TI - [Not Available]. PMID- 20288495 TI - [Not Available]. PMID- 20288497 TI - [Not Available]. PMID- 20288498 TI - [Not Available]. PMID- 20288499 TI - [Not Available]. PMID- 20288500 TI - IMPROVED artificial hand. PMID- 20288501 TI - Bronchogenic carcinoma. PMID- 20288503 TI - Treatment of a shock by intra-arterial infusion. PMID- 20288502 TI - Lessons from military psychiatry for civilian psychiatry. PMID- 20288504 TI - Tetanus in the United States Army in World War II. PMID- 20288505 TI - The psychiatrist in an armored division. PMID- 20288507 TI - Improvised methods of management of compound fractures of leg. PMID- 20288506 TI - A case of retroperitoneal tumor. PMID- 20288508 TI - Tuberculosis at a prisoner of war hospital. PMID- 20288509 TI - Failure of atabrine to cause eosinophilia. PMID- 20288510 TI - Severe throat angina. PMID- 20288511 TI - Hypertrophy of the male breast associated with recovery from starvation. PMID- 20288512 TI - Determination of qualitative night blindness. PMID- 20288513 TI - A light-weight end-bearing thigh bucket. PMID- 20288514 TI - Experiment with the suction socket for above-knee amputees. PMID- 20288515 TI - Medicine at the crossroads. PMID- 20288516 TI - Acute coronary insufficiency; a new concept of acute coronary diseases. PMID- 20288517 TI - Penicillin therapy in relapsing fever; report of four cases. PMID- 20288518 TI - Multiple pulmonary calcifications. PMID- 20288519 TI - A technique for root canal therapy and root resection as an aid to the problems of a dental officer afloat. PMID- 20288520 TI - Emotional disturbances encountered in carrier pilots. PMID- 20288521 TI - Repair of soft tissue defects of the foot. PMID- 20288522 TI - Vitamin-deficiency diseases in allied prisoners of the Japanese. PMID- 20288523 TI - Subnormal intelligence in the maladjusted naval trainee; problems in recognizing low intelligence. PMID- 20288524 TI - Symptoms and management of arterial hypertension among naval personnel. PMID- 20288525 TI - The treatment of renal colic with special emphasis on crystalluria. PMID- 20288526 TI - Chronic asthma; results of treatment in 100 cases. PMID- 20288527 TI - The wartime log of a United States navy hospital ship to June 1943. PMID- 20288528 TI - Primary adenocarcinoma of the appendix with development of mucus fistula. PMID- 20288529 TI - Hemorrhagic ulcerative gastrojejunitis thirty years after gastroenterostomy for congenital pyloric stenosis. PMID- 20288530 TI - Rat-bite fever. PMID- 20288531 TI - Hyperergy to nicotine. PMID- 20288532 TI - Duodenal ulcer and hookworm infestation; diagnostic and military medico-legal problem. PMID- 20288533 TI - Use of Wangensteen suction aboard ship. PMID- 20288534 TI - Long-term observation of Plasmodium vivax malaria in the returned serviceman. PMID- 20288535 TI - Observations on the dispersal of DDT from aircraft for the control of mosquitoes. PMID- 20288536 TI - The spread of influenza and encephalitis. PMID- 20288537 TI - Acceleration of charged atomic particles. PMID- 20288538 TI - Experimental diabetes mellitus. PMID- 20288539 TI - Recording of potential gradients in the atmosphere. PMID- 20288540 TI - Science in the U.S.S.R. PMID- 20288541 TI - Biological synthesis of purines and pyrimidines. PMID- 20288542 TI - Recent advances in phycology, with special reference to the Southern Hemisphere. PMID- 20288543 TI - On a simple demonstration of the reversible photochemical properties of tungstic acid. PMID- 20288544 TI - Activation of prothrombin. PMID- 20288545 TI - The nitrogen-fixing activity of leagume root nodules. PMID- 20288546 TI - An alternating current probe for measurement of magnetic fields. PMID- 20288547 TI - Vacuum exposure holder for microradiography. PMID- 20288548 TI - Growth of drops formed in a Wilson cloud chamber. PMID- 20288549 TI - Boron trifluoride neutron detector for low neutron intensities. PMID- 20288550 TI - A pulse analyser for nuclear research. PMID- 20288551 TI - A gas blending system. PMID- 20288552 TI - An electrical network for the solution of secular equations. PMID- 20288553 TI - The use of the expansion of gases in a centrifugal field as cooling process. PMID- 20288554 TI - A laboratory four-channel electronic switch. PMID- 20288555 TI - A device for plotting rays in a stratified medium. PMID- 20288557 TI - A stable selective audio amplifier. PMID- 20288556 TI - The synchronization of auxiliary apparatus with a betatron. PMID- 20288558 TI - An electrophoresis apparatus using parabolic mirrors. PMID- 20288559 TI - Duralumin window beta-ray counter. PMID- 20288560 TI - Remote control betatron target positioner. PMID- 20288561 TI - Note on the soldering of beryllium. PMID- 20288562 TI - Energy sensitivity of fast neutron counters. PMID- 20288563 TI - Spiral chronograph for measurement of single millisecond time intervals with microsecond accuracy. PMID- 20288564 TI - A helium cryostat. PMID- 20288565 TI - A variable speed rotational viscosimeter. PMID- 20288566 TI - An automatic recording spectrophotometer. PMID- 20288567 TI - A simple micromanometer. PMID- 20288568 TI - The preparation of pressed Ra + Be neutron sources. PMID- 20288569 TI - Comparison of supersonic intensities by means of a magneto-striction gauge. PMID- 20288570 TI - The Bodenstein quartz spiral manometer. PMID- 20288571 TI - On memory and childhood amnesia. PMID- 20288572 TI - Notes on The Ice Man Cometh. PMID- 20288573 TI - Study of a psychopathic personality in Guatemala. PMID- 20288574 TI - Cultural dynamics of sex; a study in culture and personality. PMID- 20288575 TI - Witches and psychiatrists. PMID- 20288576 TI - The concept of culture and the psychosomatic approach. PMID- 20288577 TI - Medical philosophy; from the viewpoint of a psychiatrist. PMID- 20288578 TI - We must nurse people better. PMID- 20288580 TI - Nursing in Poland. PMID- 20288579 TI - Surgical treatment of hypertension by lumbodorsal splanchnicectomy. PMID- 20288581 TI - Nursing care in air ambulances. PMID- 20288582 TI - Ventricular drainage; procedures and nursing care. PMID- 20288583 TI - What is expert nursing care? a nursing director's viewpoint. PMID- 20288585 TI - Cerebral arteriosclerosis; with little strokes that cause a slow death. PMID- 20288584 TI - Neuropsychiatry in an Army hospital. PMID- 20288586 TI - Perineal care. PMID- 20288587 TI - The skills of psychiatric nursing. PMID- 20288588 TI - The influence of hypersensitivity on endogenous uveal disease. PMID- 20288589 TI - A contribution to the knowledge of ocular siderosis and posterior degenerative pannus. PMID- 20288590 TI - Accommodative astigmatism. PMID- 20288591 TI - Involvement of the orbit in chronic inflammation of the frontal sinus. PMID- 20288593 TI - Pressure effects in contact lenses. PMID- 20288592 TI - Observations on 300 consecutive cases of ocular war injuries. PMID- 20288594 TI - Plastic visual test plates. PMID- 20288595 TI - Ciliary dilation and vitreous recession in cataract extraction. PMID- 20288597 TI - Systemic findings in retinitis pigmentosa. PMID- 20288596 TI - The observation and correlation of scientific data. PMID- 20288598 TI - Ocular changes in rats on amino-acid (valine) deficient diet. PMID- 20288599 TI - Hydrogen-ion concentration of the aqueous. PMID- 20288600 TI - Influence of sympathomimetic drugs on the regenerative processes of the ocular epithelia. PMID- 20288601 TI - Traumatic occlusion of the central retinal artery. PMID- 20288602 TI - Diathermy treatment in retinal angiomatosis. PMID- 20288603 TI - Vascular disease associated with angioid streaks of the retina and pseudoxanthoma elasticum. PMID- 20288604 TI - A comparison of the ocular signs in children and adults suffering from subdural hematoma. PMID- 20288605 TI - A method of entoptic scotometry. PMID- 20288606 TI - Experience in operations on the superior and inferior oblique. PMID- 20288607 TI - Some experimental and clinical observations concerning stereopsis. PMID- 20288608 TI - Advances in the care of muscle anomalies. PMID- 20288609 TI - What kind of education? PMID- 20288610 TI - Post-fluorescein test in contact lens fitting. PMID- 20288611 TI - An experience with industrial vision problems. PMID- 20288612 TI - Effect of quality of illumination and distance of observation upon performance in the Ishihara test. PMID- 20288613 TI - Absence of accommodation; a case report. PMID- 20288614 TI - An outline of motor vehicle tests for license applicants in California. PMID- 20288616 TI - [Not Available]. PMID- 20288615 TI - [Not Available]. PMID- 20288620 TI - Some observations on the symptomatology and diagnosis of cases of proptosis. PMID- 20288617 TI - [Not Available]. PMID- 20288621 TI - The influence of intra-ocular pressure on the rate of drainage of aqueous humour; stabilization of intra-ocular pressure or of aqueous flow? PMID- 20288622 TI - A case of bilateral genuine iris-atrophy. PMID- 20288623 TI - Mepacrin and the eye. PMID- 20288624 TI - On glaucoma. PMID- 20288625 TI - Speed and comprehension in reading. PMID- 20288626 TI - The psychology of seeing. PMID- 20288628 TI - Light for living. PMID- 20288627 TI - The responsibilities and opportunities of the optometrist in eye injury cases. PMID- 20288629 TI - A simple criterion for quality in lighting. PMID- 20288630 TI - The importance of phoria measurements in industrial vision. PMID- 20288631 TI - Favorable prognosis for myopia reduction. PMID- 20288632 TI - Simplified fitting of contact lenses. PMID- 20288633 TI - Visual psychology. PMID- 20288634 TI - Color vision and recent developments in color vision testing. PMID- 20288635 TI - Contact lens impression techniques. PMID- 20288636 TI - Anesthesia in contact lens work; an evaluation. PMID- 20288637 TI - The education of the deaf; the Book Mart, being a list of books on the deaf, speech and speech-reading, the language of signs etc., now in print. PMID- 20288638 TI - Symposium on noise. PMID- 20288639 TI - A review of tuberculosis in the field of otolaryngology for the past year. PMID- 20288640 TI - Noise in industry. PMID- 20288641 TI - Unrecognized battle noise trauma. PMID- 20288642 TI - Ear defenders. PMID- 20288643 TI - A study of cases of acoustic trauma from a medicolegal standpoint, and a comparison of patterns of deafness. PMID- 20288644 TI - Otolaryngology in World War II. PMID- 20288645 TI - Studies in serum electrolytes; changes in blood and body fluids in prolonged fasting. PMID- 20288646 TI - Lymphoblastomatous involvement of nonlymphoid organs. PMID- 20288647 TI - A study of various methods of stool examination in the diagnosis of schistosomiasis japonica. PMID- 20288648 TI - Pulmonary embolism in nonsurgical patients with prostatic thrombosis. PMID- 20288649 TI - Infection with Corynebacterium pyogenes in man. PMID- 20288650 TI - Diffuse osteoid replacement of the bone marrow; report of case. PMID- 20288651 TI - Erythroid multiple myeloma. PMID- 20288653 TI - Simplified determination of blood volume. PMID- 20288652 TI - Determination of Rh-antibodies and blood grouping by the capillary method. PMID- 20288654 TI - Zinc in human tissues; detection and determination by dithizone. PMID- 20288655 TI - Preparation of potent blood grouping serums. PMID- 20288656 TI - A comparison of red blood cell counting technics. PMID- 20288657 TI - A simplified method for embedding cellular contents of body fluids in paraffin. PMID- 20288658 TI - An improved holder for non-protein nitrogen digestion tubes. PMID- 20288659 TI - Development of bone marrow in adult animals. PMID- 20288660 TI - Pathologic action of DDT and certain of its analogs and derivatives. PMID- 20288661 TI - Repair in the skin of guinea pigs subsequent to applications of 20 methylcholanthrene. PMID- 20288662 TI - Histoplasmosis in infancy; the pathologic picture as seen in one case. PMID- 20288663 TI - Congenital tularemia. PMID- 20288664 TI - Ainhum; report of a case in which the patient was a white woman with diabetes mellitus. PMID- 20288665 TI - Metastatic calcification. PMID- 20288666 TI - Pulmonary calcifications and sensitivity to histoplasmin in Charleston, S. C. PMID- 20288667 TI - Supplements of vitamin A and of carotene during pregnancy; their effect on the levels of vitamin A and carotene in the blood of mother and of newborn infant. PMID- 20288668 TI - Effect of measles on the nephrotic syndrome. PMID- 20288670 TI - Mirror movements. PMID- 20288669 TI - Duplication of the rectum (enterogenous cyst or diverticulum). PMID- 20288671 TI - Agenesis of corpus callosum as a possible sequel to maternal rubella during pregnancy. PMID- 20288672 TI - Agranulocytosis in childhood; report of a case with serial bone marrow studies. PMID- 20288673 TI - Laurence-Moon-Biedl syndrome. PMID- 20288674 TI - Development of heart block in the neonatal period. PMID- 20288675 TI - Psychiatric aspects of the medical management of diabetes mellitus in children. PMID- 20288676 TI - The fate of injected particulate antigen in relation to the formation of antibodies. PMID- 20288677 TI - A chick embryo technic for chemotherapeutic studies in tuberculosis; results with streptomycin and other compounds. PMID- 20288678 TI - Influence of various hormones on the resistance of Swiss mice to murine poliomyelitis virus. PMID- 20288679 TI - Neurogenic intestinal obstruction in infancy; a clinical and pathologic study. PMID- 20288681 TI - Effects of maternal malnutrition on fetal development. PMID- 20288680 TI - Management of anuria resulting from sulfonamide therapy. PMID- 20288682 TI - Functional hepatic changes associated with fatty metamorphosis of the liver. PMID- 20288683 TI - Diagnosis of tetralogy of Fallot and indications for operation. PMID- 20288684 TI - Congenital tuberculosis. PMID- 20288685 TI - Complications of localized pulmonary emphysema in childhood. PMID- 20288686 TI - The etiology and the effects of minor grades of anaemia in young children; studies at a group of war-time day nurseries. PMID- 20288687 TI - Dermatomyositis in childhood; a report of four cases. PMID- 20288688 TI - The relationship of the blood pyruvic acid level to deficiency states in infancy and childhood. PMID- 20288689 TI - Acute bilateral suprarenal haemorrhage. PMID- 20288690 TI - The treatment of enuresis in children by means of chorionic gonadotropin. PMID- 20288691 TI - Differentiation between muscular dystrophy and atrophy. PMID- 20288692 TI - The importance of prolonged rest in bed after acute cardiac inflammation in children. PMID- 20288693 TI - Poliomyelitis: lobar pneumonia. PMID- 20288694 TI - Poliomyelitis, bulbar, encephalitic. PMID- 20288696 TI - Congenital hemolytic anemia. PMID- 20288697 TI - Bilateral renal calculi. PMID- 20288695 TI - Pneumoccoccus meningitis in infants and children; a report on the use of combined sulfonamides and penicillin therapy. PMID- 20288698 TI - Asthma; report of a fatal case. PMID- 20288699 TI - Loeffler's syndrome associated with ascaris lumbricoides. PMID- 20288700 TI - Leukemia with an associated septicemia. PMID- 20288701 TI - Fatality due to ascariasis. PMID- 20288702 TI - [Purulent meningitis]. PMID- 20288703 TI - United to fight cerebral palsy. PMID- 20288704 TI - Training restless teen-agers. PMID- 20288705 TI - Speech training standards. PMID- 20288706 TI - I face the future. PMID- 20288707 TI - The school child with heart disease. PMID- 20288708 TI - Oregon's adventure in special education. PMID- 20288709 TI - Education for the exceptional child in Dade County, Florida. PMID- 20288710 TI - Changing concepts of quarantine as a control measure. PMID- 20288712 TI - New York State Association of School Physicians. PMID- 20288711 TI - Rapid hemoglobin determinations on school children. PMID- 20288713 TI - The future of the school health program; the control of communicable diseases in school children. PMID- 20288714 TI - The future of the school health program; the school physician's responsibility. PMID- 20288715 TI - The future of the school health program; the school nurse-teacher's responsibility. PMID- 20288716 TI - The future of the school health program; mental hygiene. PMID- 20288717 TI - Correlating health education and health service in the school health program; the function of the school nurse teacher. PMID- 20288718 TI - A school health unit. PMID- 20288719 TI - SPECIFICATIONS; school health units. PMID- 20288720 TI - Duties and functions of the health coordinator at the secondary level. PMID- 20288721 TI - The physician's job in the school health program. PMID- 20288722 TI - The plus sphere test. PMID- 20288724 TI - The responsibility of the medical profession for child development. PMID- 20288725 TI - Twelve years of tuberculosis case finding among high school pupils. PMID- 20288723 TI - The Denver Area Rheumatic Fever Diagnostic Service; observations on 2,000 cases seen during the first two years; preliminary report. PMID- 20288726 TI - Treatment of pediculus capitis in school children with DDT powder. PMID- 20288727 TI - The sex hormones. PMID- 20288728 TI - Bacillus Calmette Guerin. PMID- 20288729 TI - Socialized medicine in Mexico. PMID- 20288730 TI - The medical aspects of atomic energy. PMID- 20288731 TI - Progress in allergy therapy. PMID- 20288732 TI - Diphtheria. PMID- 20288733 TI - 2,4-D toxicity; toxicity towards certain species of fish. PMID- 20288734 TI - New galenical preparations from flax seeds. PMID- 20288735 TI - Progress in fungous disease therapy. PMID- 20288737 TI - The general medical aspects of atomic energy. PMID- 20288736 TI - Progress in allergy therapy. PMID- 20288738 TI - Suggestions for new objectives in pharmaceutical education. PMID- 20288739 TI - Pharmaceutical engineering. PMID- 20288740 TI - Engineering problems of the pharmaceutical manufacturer. PMID- 20288741 TI - Pharmaceutical education for the future. PMID- 20288742 TI - Achievement and predictive testing in the pharmaceutical survey. PMID- 20288743 TI - The predictive testing program of the pharmaceutical survey. PMID- 20288744 TI - The present status of graduate education in pharmacy. PMID- 20288745 TI - Graduate education in pharmacy. PMID- 20288746 TI - Graduate instruction in pharmaceutical chemistry. PMID- 20288747 TI - Graduate work in pharmacognosy. PMID- 20288749 TI - Undergraduate and graduate research in pharmacology in colleges of pharmacy. PMID- 20288748 TI - Graduate work in pharmacology. PMID- 20288750 TI - Industry's requirements of pharmacology. PMID- 20288751 TI - What are industry requirements of pharmacognosy research and teaching? PMID- 20288752 TI - Chemurgic research with drug plants. PMID- 20288754 TI - Biochemistry in the pharmacy curriculum. PMID- 20288753 TI - Biochemistry in the pharmacy curriculum; optional or required subject. PMID- 20288755 TI - A discussion on the subject matter for biochemistry. PMID- 20288756 TI - Dispensing pharmacy as the culmination of the pharmaceutical curriculum. PMID- 20288757 TI - The prescription forum as a method of teaching incompatibilities. PMID- 20288758 TI - Pharmaceutical economics in the postwar curriculum. PMID- 20288759 TI - The American Institute of the History of Pharmacy and the A. Ph. A. Section on Historical Pharmacy. PMID- 20288760 TI - The history of military pharmacy in the United States; a progress report. PMID- 20288761 TI - NITROGEN mustard drugs in neoplastic diseases. PMID- 20288763 TI - NEW N. F. VIII drugs. PMID- 20288762 TI - IODINE tincture 2 percent U.S.P. XIII. PMID- 20288764 TI - SYNTHETIC benzylpenicillin. PMID- 20288765 TI - DISOPROPYL fluorophosphate in glaucoma. PMID- 20288766 TI - PROPYL thiouracil in hyperthyroidism. PMID- 20288767 TI - Progress of research in pharmacology. PMID- 20288768 TI - Penicillin dusting powders. PMID- 20288769 TI - Fungous disease therapy. PMID- 20288770 TI - Hospital practice in Great Britain. PMID- 20288771 TI - Instrument disinfecting solutions. PMID- 20288772 TI - A new concept of the role of hydrogen ion concentration and buffer system in the preparation of ophthalmic solutions. PMID- 20288773 TI - The stability of commercial crystalline sodium penicillin in solutions. PMID- 20288774 TI - Quaternary amonium compounds as preservatives. PMID- 20288775 TI - A contribution to the pharmacology of succinic acid and its sodium and magnesium salts. PMID- 20288776 TI - Laxative action of succinates in man. PMID- 20288777 TI - Notes on the pharmacology of sodium fluoroacetate; compound 1080. PMID- 20288778 TI - The colorimetric determination of bismuth in pharmaceutical preparations and in biological material. PMID- 20288779 TI - Emulsion of methyl salicylate. PMID- 20288781 TI - Streptomycin and drug fastness. PMID- 20288780 TI - METHIONINE for liver injury. PMID- 20288782 TI - Investigations on the autoxidation of diethyl ether; polarographic investigations. PMID- 20288783 TI - The activity of sulphanilylbenzamide against Streptococcus haemolyticus infection in mice. PMID- 20288785 TI - Dried alumina. PMID- 20288784 TI - The tuberculostatic activity of substituted benzoic acids. PMID- 20288786 TI - The polarographic determination of oestrone. PMID- 20288787 TI - A polarographic study of alkaloids. PMID- 20288788 TI - An investigation into the action of fungicides; preparation of suspensions of mould spores, and the effect of clumps on the accuracy of sampling. PMID- 20288789 TI - The delayed absorption and excretion of penicillin by rabbits, following intramuscular injection of a suspension in beeswax and oil. PMID- 20288790 TI - THERAPEUTIC use of vitamin K. PMID- 20288791 TI - MORE dogs or better babies? A survey of the current status of animal experimentation. PMID- 20288792 TI - RELATIONSHIP of vitamin C to the adrenal cortex. PMID- 20288793 TI - BLOOD and its disorders; physiology and diagnosis. PMID- 20288794 TI - MALE climacteric. PMID- 20288795 TI - POSTOPERATIVE activity and thrombo-embolism. PMID- 20288796 TI - ANTICOAGULANTS and postpartum bleeding. PMID- 20288797 TI - SULFONAMIDE mixtures. PMID- 20288798 TI - PENTOTHAL sodium. PMID- 20288799 TI - Application of the radioactive red cell method for determination of blood volume in humans. PMID- 20288800 TI - Sodium therapy of experimental tourniquet shock. PMID- 20288801 TI - The importance of the afferent nervous factor in experimental traumatic shock; the effect of chronic deafferentation. PMID- 20288802 TI - Blood pressure of the rat during acute and chronic choline deficiency. PMID- 20288803 TI - Is prothrombin a unitary principle or a complex? PMID- 20288804 TI - The distribution and movements of carbon dioxide and chloride between cells and serum of oxygenated human blood. PMID- 20288805 TI - The coronary circulation in the dog. PMID- 20288807 TI - Effects of hypothermia upon the specific gravity and proteins of the blood of chickens. PMID- 20288806 TI - The metabolism of glucose in starvation and water deprivation. PMID- 20288808 TI - The effect of restricted caloric intake on the longevity of rats. PMID- 20288809 TI - Effects in young men consuming restricted quantities of B-complex vitamins and protein, and changes associated with supplementation. PMID- 20288810 TI - Blood flow in the bronchial artery of the anesthetized dog. PMID- 20288811 TI - The circular components of the muscularis muscosae of the small intestine of the dog. PMID- 20288812 TI - Cholinesterases in rat tissues and the site of serum nonspecific cholinesterase production. PMID- 20288813 TI - Renal hyperemia in dogs induced by oral administration of cinchona alkaloids. PMID- 20288814 TI - Influence of the thyroid hormone on the effector systems of the mammalian heart. PMID- 20288815 TI - Further studies on antigonadotrophin formation following gonadotrophic hormone administration. PMID- 20288816 TI - The difference in action of parasympathetic drugs in application to serosa or mucosa of the isolated intestine. PMID- 20288817 TI - Studies on permeability of the leucocyte. PMID- 20288818 TI - A study of coronary flow under conditions of hemorrhagic hypotension and shock. PMID- 20288819 TI - Phasic changes in inferior cava flow of intravascular origin. PMID- 20288820 TI - Comparison of changes in inferior cava flow after hemorrhage and circulatory failure following transfusion. PMID- 20288821 TI - Growth. PMID- 20288822 TI - Developmental physiology. PMID- 20288823 TI - Reproduction. PMID- 20288824 TI - Metabolic functions of the endocrine glands. PMID- 20288825 TI - The physiology of supporting tissue. PMID- 20288826 TI - Muscle. PMID- 20288827 TI - Exercise. PMID- 20288828 TI - The visceral functions of the nervous system. PMID- 20288829 TI - Digestive system. PMID- 20288830 TI - Kidney. PMID- 20288831 TI - Peripheral circulation. PMID- 20288832 TI - Heart. PMID- 20288833 TI - Derivatives of blood plasma. PMID- 20288834 TI - Blood gas transport. PMID- 20288835 TI - Water metabolism. PMID- 20288836 TI - Physiological effects of heat and cold. PMID- 20288837 TI - The respiratory system. PMID- 20288838 TI - Nerve and synaptic conduction. PMID- 20288839 TI - Bioelectric potentials in the nervous system and in muscle. PMID- 20288840 TI - Electrical activity of the brain. PMID- 20288841 TI - The somatic functions of the central nervous system. PMID- 20288842 TI - Special senses, cutaneous sensation. PMID- 20288843 TI - The experimental neurosis. PMID- 20288844 TI - Permeability. PMID- 20288845 TI - Physiological aspects of genetics. PMID- 20288846 TI - Defense mechanisms. PMID- 20288847 TI - Pharmacology. PMID- 20288848 TI - [Not Available]. PMID- 20288849 TI - [Not Available]. PMID- 20288850 TI - [Not Available]. PMID- 20288851 TI - [Not Available]. PMID- 20288852 TI - [Not Available]. PMID- 20288853 TI - [Not Available]. PMID- 20288854 TI - [Not Available]. PMID- 20288855 TI - Disturbances of function induced by lewisite (2-chlorvinyldichlorarsine). PMID- 20288857 TI - Experimental observations on the structure of the bone marrow. PMID- 20288856 TI - Atrophy of the supraoptic and paraventricular nuclei after interruption of the pituitary stalk in dogs. PMID- 20288858 TI - A study of arsine poisoning. PMID- 20288859 TI - Avidity of anti-A agglutinating sera. PMID- 20288860 TI - The effect of BAL on the excretion of arsenoxides. PMID- 20288861 TI - Adaptation-level as frame of reference for prediction of psychophysical data. PMID- 20288862 TI - The role of the optic cortex of the dog in the retention of learned responses to light; conditioning with light and food. PMID- 20288863 TI - Visual field factors in the perception of direction. PMID- 20288864 TI - Effects of benzedrine sulfate (amphetamine) on psychomotor performance. PMID- 20288865 TI - Time-error as a function of the method of experimentation. PMID- 20288866 TI - Critical flicker frequency and the reversals of apparent movement in Lissajous figures. PMID- 20288867 TI - Group experiments and demonstrations in learning. PMID- 20288869 TI - Reenforcement of perception. PMID- 20288868 TI - The third dimension in the projection of motion pictures. PMID- 20288870 TI - Some implicates of occasionalism concerning time and memory. PMID- 20288871 TI - Research on personnel selection in the Royal Navy and the British Army. PMID- 20288872 TI - An analysis of duties performed by clinical psychologists in the Army. PMID- 20288873 TI - The place of experimental psychology in the undergraduate curriculum. PMID- 20288875 TI - Naval aviation psychology; the central research groups. PMID- 20288874 TI - A comparison of ASTP psychology graduates with other groups in the AAF Classification School. PMID- 20288876 TI - Professional frustration in government psychologists. PMID- 20288877 TI - History of psychological studies of the design and operation of equipment. PMID- 20288878 TI - Psychology at the Naval Research Laboratory. PMID- 20288879 TI - Psychological research on equipment design in the AAF. PMID- 20288880 TI - Tests used in Veterans Administration Advisement Units. PMID- 20288881 TI - The calibration of test items. PMID- 20288883 TI - Notehand for psychologists. PMID- 20288882 TI - In defense of military psychology. PMID- 20288884 TI - A comparative study of the level of aspiration of normal and of neurotic persons. PMID- 20288885 TI - Psychological aspects of rehabilitation in cases of brain injury. PMID- 20288886 TI - An attempt to test high-grade intelligence. PMID- 20288887 TI - On physiology and consciousness. PMID- 20288888 TI - The recalling of thoughts. PMID- 20288889 TI - The present House of Commons: its educational and social background. PMID- 20288890 TI - Industrial use of the Ishihara tests for color blindness. PMID- 20288891 TI - A new method for reading the employment questionnaire. PMID- 20288892 TI - Differences in interests among public administrators. PMID- 20288893 TI - Reliability and validity of the Kopas wage earner battery of tests. PMID- 20288894 TI - Luckiesh and Moss on reading illumination. PMID- 20288895 TI - Some evidence on the validity of the Cardall test of practical judgment. PMID- 20288896 TI - Interests and general educational development. PMID- 20288898 TI - The special leadership training program at the Signal Corps Officer Candidate School. PMID- 20288897 TI - The Shipley-Hartford Retreat scale as a measure of intellectual impairment for military prisoners. PMID- 20288899 TI - A note on popular pseudopsychological beliefs in 1923 and in 1946. PMID- 20288900 TI - Applied research that might have been. PMID- 20288901 TI - The Veterans Administration and clinical psychology. PMID- 20288902 TI - The psychiatrist and the psychologist. PMID- 20288903 TI - Reflections from a branch office. PMID- 20288904 TI - The role of the clinical psychologist in a Veterans Administration Mental Hygiene Clinic. PMID- 20288905 TI - The clinical psychology program at Winter V. A. Hospital, the Menninger Foundation, and the University of Kansas. PMID- 20288906 TI - Training clinical psychologists in the Veterans Administration. PMID- 20288907 TI - Research planning in neuropsychiatry and clinical psychology in the Veterans Administration. PMID- 20288908 TI - Research on the selection of clinical psychologists. PMID- 20288909 TI - Audio-visual aids for mental hygiene and psychiatry. PMID- 20288910 TI - The use of a sentence completion test for the diagnosis of personality. PMID- 20288911 TI - On the interpretation of personality profiles. PMID- 20288912 TI - A comparative study of motivations as revealed in thematic apperception stories and autobiography. PMID- 20288913 TI - Directive psychotherapy; constitutional analysis. PMID- 20288914 TI - Contributions of clinical psychology to military neuropsychiatry in an Army psychiatric hospital. PMID- 20288915 TI - Nondirective vocational counseling of prison inmates. PMID- 20288916 TI - A report of data on the job qualification inventory. PMID- 20288918 TI - Individualized and meaningful instruction in arithmetic. PMID- 20288917 TI - Mental growth and development at the college level. PMID- 20288919 TI - Active versus blank responses to multiple-choice items. PMID- 20288920 TI - Dramatic dialogues for simultaneous treatment of reading and personality problems. PMID- 20288921 TI - Some effects of radio-listening on the efficiency of reading-type study activities. PMID- 20288922 TI - The speed of object recognition and of word recognition in groups of passing and failing pupils. PMID- 20288923 TI - Conditioning as a function of the time between conditioned and unconditioned stimuli. PMID- 20288924 TI - The relation between distribution of practice and learning efficiency in psychomotor performance. PMID- 20288925 TI - Studies in spatial learning; two paths to the same location and two paths to two different locations. PMID- 20288926 TI - Studies in spatial learning; the transfer of place learning to other starting paths. PMID- 20288927 TI - On certain conditions controlling the realism and irrealism of aspirations. PMID- 20288928 TI - Experimental studies of the judgmental theory of feeling; the influence of nonmanipulative responses. PMID- 20288929 TI - The modification of judgments in a group situation. PMID- 20288930 TI - Proactive inhibition in the recognition of nonsense syllables. PMID- 20288931 TI - An apparatus for the measurement of continuous changes in palmar skin resistance. PMID- 20288932 TI - The masking of speech. PMID- 20288933 TI - The effective use of manipulative tests in industry. PMID- 20288934 TI - The treatment of qualitative data by scale analysis. PMID- 20288935 TI - Response to Crespi's rejoinder and Conrad's reply to appraisal of opinion attitude methodology. PMID- 20288936 TI - An approach to the problem of differential prediction. PMID- 20288938 TI - Diagrams for computing tetrachoric correlation coefficients from percentage differences. PMID- 20288937 TI - The relation of multiserial eta to other measures of correlation. PMID- 20288939 TI - Test selection with integral cross score weights. PMID- 20288940 TI - Note on a reanalysis of Davis' reading tests. PMID- 20288941 TI - Quantitative psychology as a rational science. PMID- 20288942 TI - Variation in test validity with variation in the distribution of item difficulties, number of items, and degree of their intercorrelation. PMID- 20288943 TI - A first-order method for estimating correlation coefficients. PMID- 20288944 TI - A prepunched master deck for the computation of square roots on IBM electrical accounting equipment. PMID- 20288945 TI - Test selection and suppressor variables. PMID- 20288946 TI - A brief comment on Thurstone's note on a reanalysis of Davis' reading tests. PMID- 20288948 TI - The health department and medical care; Maryland Medical Care Program. PMID- 20288947 TI - The health department and medical care; responsibility of the health officer in a medical care program. PMID- 20288949 TI - The health department and medical care; group practice in preventive medicine. PMID- 20288950 TI - The health department and medical care; certain trends. PMID- 20288951 TI - Discussion of papers on the health department and medical care. PMID- 20288952 TI - Today's key to better public health service. PMID- 20288953 TI - Universal serologic reactivity with lipid antigens; basis for false positives. PMID- 20288954 TI - Colorado tick fever. PMID- 20288955 TI - The nurse's role in health education in industry. PMID- 20288956 TI - Studies of the effect of the provision of good housing on health. PMID- 20288957 TI - BCG. PMID- 20288958 TI - UNMARRIED mother. PMID- 20288959 TI - The welfare of elderly persons. PMID- 20288960 TI - Nutrition as an applied science. PMID- 20288961 TI - Epidemics before the Norman Conquest. PMID- 20288962 TI - Progress of diphtheria immunisation. PMID- 20288963 TI - NEO-NATAL infection. PMID- 20288964 TI - The evaluation of infant health services; a note on yearly comparisons. PMID- 20288965 TI - Ten-year experiment in diphtheria prevention in Sullivan County. PMID- 20288966 TI - Research with fluorine and tooth decay control. PMID- 20288967 TI - Community-wide cooperation for better health and sanitation. PMID- 20288968 TI - Cancer among Negroes. PMID- 20288969 TI - Post-war prospects in tuberculosis. PMID- 20288970 TI - Teeth and the school doctor. PMID- 20288971 TI - EDUCATION ACT, 1944. PMID- 20288972 TI - Soviet Medical Academy's new programme. PMID- 20288973 TI - The Rhine Barrier Zone. PMID- 20288974 TI - Hygiene problems in displaced persons camps in Germany. PMID- 20288975 TI - Tuberculosis--a survey of a county programme. PMID- 20288976 TI - Pulmonary injury in boiler cleaners. PMID- 20288977 TI - The experimental chemotherapy of filariasis bancrofti. PMID- 20288978 TI - Quantitative determination of Schistosoma mansoni ova in feces from patients under treatment with antimonial drugs. PMID- 20288979 TI - The treatment of Schistosomiasis mansonii; evaluation of the parasitotropic effects of fuadin and tartar emetic. PMID- 20288980 TI - Edison and roentgenology. PMID- 20288981 TI - Trend toward cancer specialization. PMID- 20288982 TI - Cancer of the eyelid treated by radiation; with consideration of irradiation cataract. PMID- 20288983 TI - Cancer of the tongue. PMID- 20288984 TI - Carcinoma of the anus. PMID- 20288985 TI - Pulmonary complications of dorsal sympathectomy. PMID- 20288986 TI - Webs and constricting bands in the upper esophagus (sideropenic dysphagia). PMID- 20288987 TI - Carcinoma of the pancreas with generalized bone metastases; report of two cases. PMID- 20288988 TI - Sickle cell anemia; case report with unusual roentgen findings. PMID- 20288989 TI - Anterior vertebral wedging frequency and significance. PMID- 20288990 TI - Solitary myeloma of bone. PMID- 20288991 TI - The recognition and significance of bacteriogenic gas in the soft tissues. PMID- 20288992 TI - A simplified method of producing the axial view of Mayer in chronic mastoiditis and attic cholesteatoma. PMID- 20288993 TI - The radium treatment of cancer of the cervix; a historical review. PMID- 20288994 TI - Aerosinusitis; with special reference to roentgen diagnosis. PMID- 20288995 TI - Roentgenologic findings in myasthenia gravis associated with thymic tumor. PMID- 20288996 TI - Myelosclerosis with leukoerythroblastic anemia. PMID- 20288997 TI - Lacunar skull (Luckenschadel) of the newborn; report of seven cases. PMID- 20288998 TI - Amebiasis; roentgen study of relatively early gastrointestinal findings. PMID- 20288999 TI - Benign ulcer of the fourth portion of the duodenum. PMID- 20289000 TI - Nephrography. PMID- 20289001 TI - Massive congenital hydronephrosis; a case report. PMID- 20289002 TI - The significance of the retracted and curved horizontal fissure of the lungs. PMID- 20289003 TI - Fractures of the ribs; with comparison of the standard and one-film two-exposure technique. PMID- 20289004 TI - Avascularization of the astragalus. PMID- 20289005 TI - Double uterus; report of a case. PMID- 20289007 TI - Oil circulation in diagnostic roentgen tubes. PMID- 20289006 TI - Biological evaluation of 20 million volt roentgen rays; decoloration of hair in mice. PMID- 20289008 TI - The evaluation of post-irradiation prognosis in cancer of the cervix. PMID- 20289009 TI - A device for sinus roentgenography with horizontal rays. PMID- 20289010 TI - The radiotherapeutic treatment of cancer corporis uteri. PMID- 20289011 TI - The size of the vaginal vault in relation to the treatment of cancer of the cervix. PMID- 20289012 TI - The effect of X-rays on ascorbic acid concentration in plasma and in tissues. PMID- 20289013 TI - The clinical, radiological and pathological aspects of pulmonary haemosiderosis. PMID- 20289014 TI - Standardised radiological pelvimetry; qualitative. PMID- 20289015 TI - Pneumonia of the lobe of the azygos vein; the report of a case. PMID- 20289017 TI - A comment on the Derby fatality. PMID- 20289016 TI - The radiological anatomy of the labyrinth. PMID- 20289018 TI - X-ray department design; a further comment. PMID- 20289019 TI - Radiographic technique and its relationship to pathology and injury. PMID- 20289020 TI - Quality of radiation in roentgen therapy. PMID- 20289021 TI - A duodenal mechanism regulating the motor and secretory activity of the stomach; its roentgenographic disturbance in duodenal ulcer. PMID- 20289022 TI - Pericardial celomic cysts. PMID- 20289023 TI - Gastrocolic fistula complicating carcinoma of the colon. PMID- 20289024 TI - Rheumatic mitral valve disease without cardiac enlargement. PMID- 20289025 TI - Unilateral paraspinal abscess. PMID- 20289026 TI - Observations on gunshot fractures of the mandible. PMID- 20289027 TI - An addition to the technic of simple breast roentgenography. PMID- 20289028 TI - Cholecystography; a comparative study of oral and intravenous contrast substances. PMID- 20289029 TI - Late changes in mucous membrane of the irradiated larynx; their radiobiological relationship to the subepithelial connective tissue and to retrogression of laryngeal carcinoma; histologic studies. PMID- 20289030 TI - Legal liability for error in diagnosis; roentgenologist and his employer held liable for a mistaken diagnosis. PMID- 20289031 TI - Radiology and the future. PMID- 20289032 TI - What's in a title? PMID- 20289033 TI - Some aspects of operative treatment of cancer recti. PMID- 20289034 TI - [Not Available]. PMID- 20289035 TI - Harelip and cleft palate; 1,000 patients submitted to operation. PMID- 20289036 TI - The differential diagnosis and treatment of tuberculomas in the lung. PMID- 20289037 TI - A case of double bladder. PMID- 20289038 TI - The clinical picture and treatment of pheochromocytomas of the suprarenal; two own cases, one with paroxysmal hypertension improved by treatment with methylthiouracil and cured by surgical intervention. PMID- 20289039 TI - [Not Available]. PMID- 20289040 TI - Postoperative blood changes with regard to shock. PMID- 20289041 TI - On acute regional enteritis. PMID- 20289042 TI - The problem of surgical arrest of massive hemorrhage in peptic ulcer. PMID- 20289043 TI - [Not Available]. PMID- 20289044 TI - [Not Available]. PMID- 20289045 TI - [Not Available]. PMID- 20289046 TI - [Not Available]. PMID- 20289047 TI - [Not Available]. PMID- 20289048 TI - [Not Available]. PMID- 20289049 TI - [Not Available]. PMID- 20289051 TI - [Not Available]. PMID- 20289050 TI - [Not Available]. PMID- 20289052 TI - [Not Available]. PMID- 20289053 TI - [Not Available]. PMID- 20289054 TI - [Not Available]. PMID- 20289055 TI - [Not Available]. PMID- 20289056 TI - [Not Available]. PMID- 20289057 TI - [Not Available]. PMID- 20289058 TI - [Not Available]. PMID- 20289059 TI - [Not Available]. PMID- 20289060 TI - [Not Available]. PMID- 20289062 TI - [Not Available]. PMID- 20289061 TI - [Not Available]. PMID- 20289063 TI - [Not Available]. PMID- 20289064 TI - [Not Available]. PMID- 20289065 TI - [Not Available]. PMID- 20289067 TI - [Not Available]. PMID- 20289066 TI - [Not Available]. PMID- 20289068 TI - Posterior colpotomy for diagnosis of pelvic diseases. PMID- 20289069 TI - Primary cyst of the round ligament. PMID- 20289070 TI - Tissue culture as a clinical aid in the diagnosis of malignant tumors. PMID- 20289071 TI - Recurrent dislocation of the patella. PMID- 20289072 TI - Common errors in burn treatment. PMID- 20289073 TI - Streptomycin therapy for bacteremia. PMID- 20289074 TI - Pyriformis syndrome in relation to sciatic pain. PMID- 20289075 TI - Hydrogen ion concentration (pH) of the vagina associated with an ectropion of the cervix (cervicitis). PMID- 20289076 TI - Significance of hyperuricemia in surgery; an introduction to current observations. PMID- 20289077 TI - End results of ruptured intervertebral discs in industry. PMID- 20289078 TI - Pregnancy in a rudimentary horn of the uterus. PMID- 20289079 TI - Tumors of the small intestine. PMID- 20289080 TI - Primary liver tumors. PMID- 20289081 TI - Spigelian hernia. PMID- 20289082 TI - Intestinal lipoma simulating carcinoma of the sigmoid colon. PMID- 20289083 TI - An unusual complication of an inguinal hernia. PMID- 20289084 TI - CRUTCH mastery. PMID- 20289085 TI - The surgical therapeutic significance of the functional behavior of thyroid nodules. PMID- 20289088 TI - Thoracic surgery in a hospital center. PMID- 20289090 TI - Compound injuries of the knee joint; treatment of noninfected knee joints. PMID- 20289094 TI - Vitamin C in gastric resection for peptic ulcer. PMID- 20289095 TI - Incised wounds of the head inflicted by bayonets. PMID- 20289096 TI - Use of small threaded wires in the treatment of fractures; fractures of the lower extremities. PMID- 20289097 TI - Use of small threaded wires in the treatment of fractures; fractures of the upper extremities. PMID- 20289098 TI - Use of small threaded wires in the treatment of fractures; their use in the fixation of bone grafts. PMID- 20289099 TI - Treatment of deep venous thrombosis with reference to subcutaneous injection of heparin and use of dicumarol. PMID- 20289100 TI - Pathognomonic sign for cyst of the knee cartilage. PMID- 20289101 TI - Progress in orthopedic surgery for 1945; conditions involving the hip joint. PMID- 20289102 TI - Progress in orthopedic surgery for 1945; conditions involving the foot and ankle. PMID- 20289103 TI - Progress in orthopedic surgery for 1945; congenital dislocation of the hip. PMID- 20289104 TI - Review of urologic surgery. PMID- 20289105 TI - Local and parenteral penicillin therapy in the treatment of recent war wounds. PMID- 20289106 TI - The closure of colostomy openings. PMID- 20289108 TI - Congenital bipartite carpal navicular. PMID- 20289107 TI - The Estlander-Abbe operation. PMID- 20289109 TI - Dysplasia epiphysialis multiplex. PMID- 20289110 TI - Sarcoma in abnormal bones. PMID- 20289111 TI - Needle biopsy in the clinical diagnosis of tumours. PMID- 20289112 TI - Renal anoxia and the traumatic uraemia syndrome. PMID- 20289113 TI - Osteitis pubis after suprapubic operations on the bladder; with a report of ten cases. PMID- 20289114 TI - Razor blade in oesophagus; transthoracic removal. PMID- 20289115 TI - Chorioncarcinoma of the testis with gynaecomastia; report of a case with early breast cancer. PMID- 20289116 TI - The Arnold-Chiari malformation. PMID- 20289117 TI - The transformation of an embryonic lipoma to a common lipoma. PMID- 20289118 TI - Massive haemorrhage from a peptic ulcer in a Meckel's diverticulum in a female child of eleven months. PMID- 20289119 TI - Amoebic granuloma of the skin. PMID- 20289120 TI - Tooth plate impacted in gullet for fifteen years; removal by transthoracic oesophagotomy. PMID- 20289121 TI - Carotid body tumours. PMID- 20289122 TI - The surgical treatment of hydrocephalus; a simple method of performing third ventriculostomy. PMID- 20289123 TI - Cerebral thromboangiitis obliterans. PMID- 20289124 TI - Supernumerary bursa of pectineus muscle simulating hernia in inguinal region. PMID- 20289125 TI - Congenital atresia of small intestine. PMID- 20289126 TI - Actinomycosis of the liver; report of an unusual case. PMID- 20289127 TI - Calcifications in living tissues. PMID- 20289128 TI - An unusual case of intussusception. PMID- 20289129 TI - Fibroma pendulum. PMID- 20289130 TI - Case of sarcoma of stomach simulating splenic tumour. PMID- 20289131 TI - A case of carcinoma of the ileocaecal valve, with formation of a spontaneous ileocaecal fistula. PMID- 20289132 TI - Multiple capillary haemangioma of the skull bones. PMID- 20289133 TI - Arteriovenous aneurysm as a complication of intertrochanteric fracture of the femur. PMID- 20289134 TI - Impending death under anesthesia. PMID- 20289135 TI - The surgical concept in hyperthyroidism. PMID- 20289136 TI - The reconditioning of spinal cord injuries. PMID- 20289137 TI - Dermoplasty of war wounds of the lower extremity. PMID- 20289138 TI - Anatomical and surgical considerations of the phrenic and accessory phrenic nerves. PMID- 20289139 TI - Prostheses for the nose. PMID- 20289140 TI - Operative technic for external and internal strabismus. PMID- 20289141 TI - Uretero-ureterostomy; anastomosis of old stump of right ureter with injured left ureter. PMID- 20289142 TI - [Not Available]. PMID- 20289143 TI - [Not Available]. PMID- 20289144 TI - [Not Available]. PMID- 20289145 TI - [Not Available]. PMID- 20289146 TI - [Not Available]. PMID- 20289147 TI - Cicatricial stenosis of the nasopharynx; correction by means of a skin graft. PMID- 20289148 TI - The use of neighboring tissues in the correction of an extensive facial deformity. PMID- 20289149 TI - The immediate repair of war wounds of the face. PMID- 20289150 TI - Restoration of the cheek by using the skin of the jaw-neck region. PMID- 20289151 TI - Classification of maxillofacial injuries. PMID- 20289152 TI - Cleft lip repair after Axhausen. PMID- 20289153 TI - Substitution of the chisel for the saw in reconstructive surgery of the nose. PMID- 20289154 TI - Another external nasal splint. PMID- 20289155 TI - Modern experiences with tubed pedicle flaps of the thigh. PMID- 20289156 TI - Ligation of the inferior vena cava in thromboembolism; report of 36 cases. PMID- 20289157 TI - Total gastrectomy; report of 89 cases. PMID- 20289158 TI - Complete fecal diversion achieved by a simple loop colostomy. PMID- 20289159 TI - The hyperfunctioning single adenoma of the thyroid. PMID- 20289160 TI - Resection of the common hepatic duct for papillary adenocarcinoma. PMID- 20289161 TI - Massive iliac bone frafts in the treatment of ununited fractures and large defects of long bones; the combined bone graft-metallic plate technique; an analysis of 91 operations in 85 patients. PMID- 20289162 TI - Coagulation thrombi in segments of artery and vein in dogs and the genesis of thromboembolism. PMID- 20289163 TI - Transplantation of the spinal cord; the problem of kyphoscoliosis with cord signs. PMID- 20289164 TI - Reconstructive surgery of the chest wall. PMID- 20289165 TI - Protective action of sulfanilamide on experimental chloroform hepatitis. PMID- 20289166 TI - Gastric carcinoma; a comparative review of the origin, diagnosis, and end-results in 583 patients. PMID- 20289167 TI - The physiologic effects of curare and its use as an adjunct to anesthesia. PMID- 20289168 TI - Preinfusion; a study in the prevention of hemorrhagic shock. PMID- 20289169 TI - Congenital atresia of the esophagus with tracheoesophageal fistula. PMID- 20289170 TI - The course of hypertension after nephrectomy for advanced unilateral renal disease. PMID- 20289171 TI - The place of radiation in the treatment of breast cancer. PMID- 20289172 TI - Transthoracic resection of carcinoma of the upper midthoracic esophagus. PMID- 20289174 TI - Internal fixation of fractures. PMID- 20289173 TI - Treatment of carcinoma of the uterine cervix. PMID- 20289175 TI - Enteric cyst of the coccygeal region; report of a case. PMID- 20289176 TI - The Rh factor; its present status and clinical importance. PMID- 20289177 TI - Clinical trial of a new synthetic heptanone analgesic (dolophine); preliminary report. PMID- 20289178 TI - Extreme shock and near death resulting from a douche. PMID- 20289179 TI - Recent advances in obstetrics; a selective survey of the literature for 1945 and 1946. PMID- 20289180 TI - Organization of the hospital medical staff from the standpoint of maintaining a high standard of professional proficiency. PMID- 20289181 TI - Temperature equalization for the relief of pain; an experimental study of the relation of thermal gradients to pain. PMID- 20289182 TI - The significance of physical fitness. PMID- 20289183 TI - Physical and nervous factors in experimental hypertension. PMID- 20289184 TI - A constant current impulse stimulator. PMID- 20289185 TI - Physical medicine in cerebral palsy. PMID- 20289186 TI - Effect of elevated body temperature on the cardiovascular system and the electrocardiogram with special emphasis on the chest leads. PMID- 20289187 TI - The scope and needs of physical medicine as seen by a newcomer. PMID- 20289188 TI - Physiotherapy; its scope in gynaecology. PMID- 20289189 TI - Anatomy; approach and application. PMID- 20289190 TI - The importance of the emotional life in relation to muscular and joint disturbances. PMID- 20289191 TI - The basis of osteopathy. PMID- 20289192 TI - The treatment of elbow injuries. PMID- 20289193 TI - Cure of insanity. PMID- 20289194 TI - Physical rehabilitation of patients with brain injuries. PMID- 20289195 TI - The objectives of occupational therapy. PMID- 20289196 TI - A critical study of analytically oriented group psychotherapy utilizing the technique of dramatization of the psychodynamics. PMID- 20289197 TI - [Not Available]. PMID- 20289198 TI - [Not Available]. PMID- 20289199 TI - [Not Available]. PMID- 20289200 TI - [Not Available]. PMID- 20289201 TI - [Not Available]. PMID- 20289202 TI - [Not Available]. PMID- 20289203 TI - [Not Available]. PMID- 20289204 TI - [Not Available]. PMID- 20289205 TI - [Not Available]. PMID- 20289206 TI - [Not Available]. PMID- 20289207 TI - [Not Available]. PMID- 20289208 TI - [Not Available]. PMID- 20289209 TI - [Not Available]. PMID- 20289211 TI - [Not Available]. PMID- 20289210 TI - [Not Available]. PMID- 20289212 TI - [Not Available]. PMID- 20289213 TI - [Not Available]. PMID- 20289214 TI - [Not Available]. PMID- 20289215 TI - [Not Available]. PMID- 20289216 TI - [Not Available]. PMID- 20289217 TI - [Not Available]. PMID- 20289218 TI - [Not Available]. PMID- 20289219 TI - [Not Available]. PMID- 20289220 TI - [Not Available]. PMID- 20289221 TI - [Not Available]. PMID- 20289222 TI - [Not Available]. PMID- 20289223 TI - [Not Available]. PMID- 20289224 TI - [Not Available]. PMID- 20289225 TI - [Not Available]. PMID- 20289226 TI - [Not Available]. PMID- 20289227 TI - [Not Available]. PMID- 20289228 TI - The intracutaneous test in cutaneous leishmaniasis. PMID- 20289229 TI - The infectivity to man of a strain of Trypanosoma rhodesiense transmitted cyclically by Glossina morsitans through sheep and antelope; evidence that man requires a minimum infective dose of metacyclic trypanosomes. PMID- 20289230 TI - Experiments with leech repellents. PMID- 20289231 TI - Failure to cure natural canine visceral leishmaniasis. PMID- 20289232 TI - Snake species recorded in the Gold Coast. PMID- 20289233 TI - Relapsing benign tertian malaria treated with 4430. PMID- 20289234 TI - The estimation of paludrine in urine. PMID- 20289235 TI - Mepacrine metabolism in recurring benign tertian malaria. PMID- 20289236 TI - A serological analysis of typhus cases in India by Weil-Felix, rickettsial agglutination and complement-fixation tests. PMID- 20289237 TI - Investigations in the chemotherapy of malaria in West Africa; sulphonamide compounds. PMID- 20289238 TI - The effect of muscular exercise in a hot moist environment on the mepacrine concentrations of blood, plasma and urine. PMID- 20289239 TI - The excretion of mepacrine in the faeces. PMID- 20289240 TI - The role of Anopheles gambiae var. melas in the transmission of malaria in the vicinity of Freetown Estuary, Sierra Leone, 1943. PMID- 20289241 TI - A new approach to trypanosomiasis. PMID- 20289242 TI - The use of avian malaria for the discovery of drugs effective in the treatment and prevention of human malaria; drugs for causal prophylaxis and radical cure or the chemotherapy of exo-erythrocytic forms. PMID- 20289243 TI - Blood and plasma concentrations of mepacrine in subjects taking suppressive and therapeutic dosages. PMID- 20289244 TI - The effect of various substances, including food, on the absorption of orally administered mepacrine hydrochloride. PMID- 20289245 TI - The absorption and excretion of paludrine in the human subject. PMID- 20289246 TI - The tuberculosis program of the Veterans Administration. PMID- 20289247 TI - The National Tuberculosis Association and its interest in the tuberculous veteran. PMID- 20289248 TI - Recent developments in tuberculosis control. PMID- 20289249 TI - Tuberculosis as an international problem. PMID- 20289250 TI - The tuberculosis experience of the United States Army in World War II. PMID- 20289251 TI - The significance of rehabilitation. PMID- 20289252 TI - Rehabilitation of the tuberculous; the program of a municipal sanatorium. PMID- 20289253 TI - Occupational therapy and rehabilitation. PMID- 20289254 TI - Streptomycin in miliary tuberculosis; its effect on the pathological lesions of generalized miliary tuberculosis in human beings. PMID- 20289255 TI - Tuberculosis in a laboratory monkey colony; its spread and its control. PMID- 20289256 TI - Tuberculosis in the Alabama state hospitals. PMID- 20289257 TI - [Not Available]. PMID- 20289258 TI - [Not Available]. PMID- 20289259 TI - [Not Available]. PMID- 20289260 TI - [Not Available]. PMID- 20289262 TI - [Not Available]. PMID- 20289261 TI - [Not Available]. PMID- 20289263 TI - [Not Available]. PMID- 20289264 TI - [Not Available]. PMID- 20289265 TI - [Not Available]. PMID- 20289266 TI - [Not Available]. PMID- 20289267 TI - [Not Available]. PMID- 20289268 TI - [Not Available]. PMID- 20289269 TI - [Not Available]. PMID- 20289270 TI - [Not Available]. PMID- 20289271 TI - [Not Available]. PMID- 20289272 TI - [Not Available]. PMID- 20289273 TI - [Not Available]. PMID- 20289274 TI - [Not Available]. PMID- 20289275 TI - [Not Available]. PMID- 20289276 TI - [Not Available]. PMID- 20289277 TI - [Not Available]. PMID- 20289278 TI - [Not Available]. PMID- 20289279 TI - [Not Available]. PMID- 20289280 TI - [Not Available]. PMID- 20289281 TI - [Not Available]. PMID- 20289282 TI - [Not Available]. PMID- 20289283 TI - [Not Available]. PMID- 20289284 TI - [Not Available]. PMID- 20289285 TI - [Not Available]. PMID- 20289286 TI - [Not Available]. PMID- 20289287 TI - [Not Available]. PMID- 20289288 TI - [Not Available]. PMID- 20289289 TI - [Not Available]. PMID- 20289290 TI - Transmission of experimental syphilis from mouse to mouse; absence of Spirocheta pallida and of pathologic changes in presence of successful inoculation. PMID- 20289291 TI - Six- to twelve-month follow-up results in early syphilis treated by a twenty-day intensive arsenobismuth system. PMID- 20289292 TI - The treatment of early syphilis by the twenty-six-week mapharsen-bismuth schedule. PMID- 20289293 TI - Reactions to twenty-day intensive therapy with mapharsen and bismuth for syphilis with a note on the use of BAL in their management. PMID- 20289294 TI - Dichlorophenarsine hydrochloride in the treatment of syphilis. PMID- 20289295 TI - Treatment of paroxysmal hemoglobinuria with penicillin; report of a case. PMID- 20289296 TI - The clinical, radiologic, and pathologic aspects of late pulmonary syphilis; effects of penicillin therapy. PMID- 20289297 TI - A proposed clerical system for a city venereal disease control program. PMID- 20289298 TI - The present status of immunity and allergy in syphilis. PMID- 20289299 TI - The Weltmann serum coagulation reaction in syphilis. PMID- 20289300 TI - Nonspecific serologic tests for syphilis. PMID- 20289301 TI - Practical aspects of verification tests for syphilis in office practice. PMID- 20289302 TI - The problem of positive serologic tests for syphilis in lupus erythematosus; with report of three cases. PMID- 20289303 TI - Hemophilia in a family of dogs. PMID- 20289304 TI - The effects of season on the spermatogenic activity and fertility of dairy bulls used in artificial insemination. PMID- 20289305 TI - The effect of penicillin on cows infected with Brucella abortus. PMID- 20289306 TI - Brooderstove-residue burns on turkey poults. PMID- 20289307 TI - Form variation in Salmonella pullorum and its relation to X strains. PMID- 20289308 TI - The extragenital lesions of canine pyometra. PMID- 20289309 TI - Decomposition occurring in raw chicken fat. PMID- 20289310 TI - Sampling raw chicken fat for organoleptic examination. PMID- 20289312 TI - Veterinary preventive medicine in civil affairs and military government (G-5) in Northwest Europe from D-Day to V-Day. PMID- 20289311 TI - An avian retinoblastoma. PMID- 20289313 TI - Peacetime benefits from biological warfare research studies. PMID- 20289314 TI - Experimental wartime studies on rinderpest. PMID- 20289315 TI - Public health administration. PMID- 20289316 TI - MEXICAN outbreak of foot-and-mouth disease. PMID- 20289318 TI - Teat surgery. PMID- 20289317 TI - Some observations on veterinary research in Korea. PMID- 20289319 TI - Geriatrics in canine practice. PMID- 20289320 TI - Panel discussion on penicillin in small animal practice. PMID- 20289321 TI - Effect of volume of distilled water as vehicle for penicillin in treating chronic streptococcic mastitis. PMID- 20289322 TI - Arsenic content in urine from cattle dipped in arsenical solutions. PMID- 20289323 TI - Telangiectasis, sawdust, and abscesses in the livers of beef cattle. PMID- 20289324 TI - Colostrum and its value in calf raising. PMID- 20289325 TI - CONCENTRATION of veterinarians in ten countries. PMID- 20289326 TI - Minimal vascular injection of the spleen. PMID- 20289327 TI - An unusual peritoneal anomaly; a sac containing the jejunum, ileum and transverse colon. PMID- 20289328 TI - Histological studies of muscle from crooked neck dwarf fowl. PMID- 20289329 TI - Bilateral renal agenesia. PMID- 20289330 TI - Nature of functional recovery following regeneration of the oculomotor nerve in amphibians. PMID- 20289331 TI - Origin and activity of primary trophoblast giant cells during implantation (days 4-6) in the albino rat. PMID- 20289332 TI - Age changes in the deep cervical lymph nodes of 100 Wistar Institute rats. PMID- 20289333 TI - Thymic reaction following injection of colloidal pigments. PMID- 20289334 TI - The effects of small doses of diethylstilbestrol on the anterior hypophysis of thyroidectomized rats. PMID- 20289335 TI - The effect of epinephrin on the pulsation frequency of embryonic heart muscle. PMID- 20289336 TI - Phosphatase glycogen relationships in integumentary derivatives. PMID- 20289337 TI - Growth of the lumbosacral nervous system of chick embryos after the substitution of tumors for the limb periphery. PMID- 20289338 TI - Effects of use and disuse on neurosomes in skeletal muscle of the chameleon. PMID- 20289339 TI - The architecture of the Achilles tendon. PMID- 20289340 TI - Arterial anastomoses; some factors concerned in their formation. PMID- 20289341 TI - Effects of hypophysectomy upon gastric acidity of adult female rats. PMID- 20289342 TI - Anomalous right subclavian artery originating from the descending aorta. PMID- 20289343 TI - Changes in the adrenal cortex and thymus induced by different B-vitamin deficiencies. PMID- 20289345 TI - The femoral venous system. PMID- 20289344 TI - The development of plasma cells in the organs of animals receiving various antigens. PMID- 20289346 TI - Visualization of histological structure. PMID- 20289347 TI - The behavior of the femur as an elastic body. PMID- 20289348 TI - Factors influencing accumulation of histochemically detectable cholesterol in the corpus luteum of the rat. PMID- 20289349 TI - Anatomicalstudies on jet penetration of human skin for subcutaneous medication without the use of needles. PMID- 20289350 TI - Spike potentials in sensory fibers from the knee joint of the cat. PMID- 20289351 TI - Histological observations on the vitamin E-deficient rabbit heart. PMID- 20289352 TI - Vessels and nerves in the hypo physial stalk and median eminence in man. PMID- 20289353 TI - The localization of thyroxine containing radioactive iodine in the tissues of the rat. PMID- 20289354 TI - Growth changes induced by androgens in the connective tissues, sebaceous glands, hairs, muscle and melanoblasts of the skin. PMID- 20289355 TI - Hematopoiesis in the bone marrow of rats recovering from nutritional anemia. PMID- 20289356 TI - Quantitative analysis of the brain-isocortex relationship in Mammalia. PMID- 20289357 TI - The participation of various portions of the urinary bladder in normal and induced activity. PMID- 20289358 TI - The mouse ovary and its adrenocortical functions. PMID- 20289359 TI - Hypothalamic obesity in the cat. PMID- 20289360 TI - Intransplenic injections of alloxan in the rat. PMID- 20289361 TI - A study of mitochondria in dry smears of embryonic blood. PMID- 20289362 TI - Another approach to the problem of efferent fibers in dorsal roots. PMID- 20289363 TI - Intraepithelial granular cells in urinary tracts of rats infested with Trichosomoides crassicauda. PMID- 20289364 TI - Gigantism produced in normal female rats by chronic treatment with pure pituitary growth hormone; pituitary-cytological changes. PMID- 20289365 TI - Neuroectodermal neoplasms of borderline dysplastic character; a survey of different types and their relationship to normal histogenesis. PMID- 20289366 TI - Reactions of interstitial and capsule cells in autonomic ganglia to various stimuli. PMID- 20289367 TI - Protection against alloxan diabetes. PMID- 20289368 TI - Detached respiratory squames from the lung of the albino mouse. PMID- 20289369 TI - The relation of separately innervated areas of muscle to amount of shortening and strength of contraction. PMID- 20289370 TI - Histochemistry of the sebaceous glands of the rat. PMID- 20289371 TI - The distribution of alkaline phosphatase in the developing teeth of the 4-day rat. PMID- 20289372 TI - Histopathological effects of plutonium, fission products, fast and slow neutrons, and X-rays on the thymus. PMID- 20289373 TI - Histochemical comparison of the resting and exhausted cells of the pancreas and the salivary glands of the mouse and rat. PMID- 20289374 TI - The morphology and behavior of mast cells obtained from mastocytomas and cultivated in vitro. PMID- 20289375 TI - Crossed fibers in the facial nerve in human embryos and fetuses. PMID- 20289376 TI - Myelinated fibers in grey rami communicantes. PMID- 20289377 TI - The vascular pattern of the endometrium of the pregnant rhesus monkey. PMID- 20289378 TI - The effect of sulfaguanidine on reproduction in the rat. PMID- 20289379 TI - Retardation of development in the kidneys of mentally deficient patients. PMID- 20289380 TI - The vascular channels of human bone. PMID- 20289381 TI - Combined injection and dissection studies to demonstrate variations of the bronchopulmonary segments of the left upper lobe. PMID- 20289382 TI - Histological studies concerning the endocrine kidney. PMID- 20289383 TI - Hyaluronidase and the growth of malignant epithelial tumors. PMID- 20289384 TI - The adrenal glands of normal and castrated mice. PMID- 20289385 TI - Multisinusal versus nonsinusal spleens. PMID- 20289386 TI - Histological studies on nerve elements and their endings as the epithelial cells of the gastric mucosa. PMID- 20289387 TI - Localization of motor cells in the thoracic spinal cord of the rhesus monkey. PMID- 20289388 TI - Primitive bloodvessels of the spinal medulla of the rabbit injected while alive. PMID- 20289389 TI - Vascular changes in the gonopodium of poeciliid fishes during the metamorphosis of the anal fin. PMID- 20289390 TI - The relation of the temporal muscle to the form of the skull. PMID- 20289391 TI - Cytological studies on spontaneously occurring adenomata of the anterior hypophysis of the rat. PMID- 20289392 TI - Anatomical factors in senile alopecia; experimental production of baldness. PMID- 20289393 TI - Treatment of Hirschprung's disease by splanchnic block. PMID- 20289394 TI - Amethocaine or nupercaine. PMID- 20289395 TI - Spinal analgesia, with sacral escape. PMID- 20289396 TI - Curarine chloride as an adjunct to general anaesthesia. PMID- 20289397 TI - [Biochemical factors in natural selection in plants]. PMID- 20289398 TI - [Physiological sources of correlation in the structure of the human organism]. PMID- 20289399 TI - [Problems, principles and methods of ecological microbiology]. PMID- 20289400 TI - [Chlorophyll and its influence on the animal organism]. PMID- 20289401 TI - Benign encapsulated tumor of the peripheral nerves: neurinoma, perineural fibroblastoma, neurilemoma. PMID- 20289402 TI - Osteoid-osteoma; two cases and review of the pertinent literature. PMID- 20289403 TI - Neurosurgical aspects of low back pain. PMID- 20289404 TI - Osteomyelitis of the femur in an infant. PMID- 20289405 TI - A surgical procedure for the painful arthritic hand. PMID- 20289406 TI - Intramedullary pin fixation; application following osteotomy in two cases. PMID- 20289407 TI - Notes on the upper extremity of the gorilla; clinical application. PMID- 20289408 TI - Postural treatment of the paralyzed deltoid muscle. PMID- 20289409 TI - Recurrent dislocation of the patella. PMID- 20289410 TI - Posterior central herniation of the intervertebral disc diagnosed after lumbosacral and sacroiliac fusion. PMID- 20289411 TI - Fibrosarcoma of the shoulder; a case report. PMID- 20289413 TI - Ainhum. PMID- 20289412 TI - The blood vessels of the gluteal region. PMID- 20289414 TI - [Not Available]. PMID- 20289415 TI - [Not Available]. PMID- 20289416 TI - [Not Available]. PMID- 20289417 TI - [Not Available]. PMID- 20289418 TI - [Not Available]. PMID- 20289419 TI - [Not Available]. PMID- 20289420 TI - [Not Available]. PMID- 20289422 TI - [Not Available]. PMID- 20289421 TI - [Not Available]. PMID- 20289423 TI - On the sensitivity of different tissues in Street strain mice to 9,10-dimethyl 1,2-benzanthracene. PMID- 20289424 TI - The induction of neoplasms in five strains of rats with acetylaminofluorene. PMID- 20289425 TI - Observations on radiation-induced lymphoid tumors of mice. PMID- 20289426 TI - Changes in the succinoxidase activity of livers from rats during the development of hepatic tumors on feeding para-dimethyl-aminoazobenzene. PMID- 20289427 TI - The production of tumors in the livers of rats fed in-methyl-para dimethylaminoazobenzene. PMID- 20289428 TI - p-Dimethylaminoazobenzene carcinogenesis with purified diets varying in content of cysteine, cystine, liver extract, protein, riboflavin, and other factors. PMID- 20289429 TI - The effect of biotin upon para-dimethylaminoazobenzene carcinogenesis. PMID- 20289430 TI - The effect of diet containing dried egg albumin upon para-dimethylaminoazobenzene carcinogenesis. PMID- 20289431 TI - Etiologic factors in carcinoma of the penis. PMID- 20289432 TI - Dialkylaminoalkyl esters of 4,4'-stilbenedicarboxylic and 4,4' dibenzyldicarboxylic acid. PMID- 20289433 TI - Isolation of the o, o'-DDT isomer from technical DDT. PMID- 20289434 TI - Organic fungicides; the preparation of some alpha-bromoacetamides. PMID- 20289435 TI - gamma-Palmitolactone and gamma-hydroxypalmitic acid. PMID- 20289436 TI - The kinetics of the reaction of methanol with 3,3'-dicarbazylphenylmethyl ion in alkaline solution. PMID- 20289437 TI - Properties of electrolytic solutions; the conductance of choline and related picrates in ethylene chloride at 25 degrees. PMID- 20289438 TI - The effect of the hydrogen ion concentration upon the salt error of the quinhydrone electrode. PMID- 20289439 TI - The reactions of the hydroxyl radical. PMID- 20289441 TI - Some steroid mercaptols. PMID- 20289440 TI - Organic antimony compounds derived from S-triazine with therapeutic and prophylactic activity in experimental trypanosomiasis. PMID- 20289443 TI - High-boiling hydrolytic derivatives of lignin. PMID- 20289442 TI - Isolation of rutin from two varieties of Forsythia. PMID- 20289444 TI - Aminosulfanilanisides. PMID- 20289445 TI - Alkylamine derivatives of fluorene. PMID- 20289446 TI - The infrared absorption spectra of liquid and gaseous morpholine. PMID- 20289447 TI - The heat of the inactivation of pepsin. PMID- 20289448 TI - Molecular weight and intrinsic viscosity of nitric triesters of corn starches and dextrins. PMID- 20289449 TI - The constitution of mesquite gum; partial hydrolysis of mesquite gum. PMID- 20289450 TI - Antispasmodics; diarylacetic acid esters of some pyridyl and piperidyl alkanols. PMID- 20289451 TI - The free energy, heat and entropy of sorption of water vapor by proteins and high polymers. PMID- 20289452 TI - The preparation and chemical composition of difluorodiphenyl-trichloroethane. PMID- 20289453 TI - Recovery of sucrose from cane blackstrap and beet molasses. PMID- 20289454 TI - A diffusion study of lignin sulfonic acids in sulfite waste liquor. PMID- 20289455 TI - The pigments of cottonseed; gossycaerulin, a blue quinonoid gossypol derivative occurring in cooked cottonseed. PMID- 20289456 TI - Intermediates in the synthesis of orotic acid from oxalacetic ester and urea. PMID- 20289457 TI - Determination of the critical concentration for micelle formation in solutions of colloidal electrolytes by the spectral change of a dye. PMID- 20289458 TI - The effect of salts on the critical concentration for the formation of micelles in colloidal electrolytes. PMID- 20289459 TI - The synthesis of pyrrolizidines. PMID- 20289460 TI - A method of calculating the boiling points of silicon compounds. PMID- 20289461 TI - The dealkylation of 4-(4-diethylamino-1-methyl-butylamino)-7-chloroquinoline, SN 7618. PMID- 20289462 TI - A new synthesis of polygalitol tetraacetate (tetraacetyl-1,5-anhydro-D-sorbitol). PMID- 20289463 TI - Conversion of alkaline-metals salts of amino acids into free amino acids. PMID- 20289464 TI - The insecticidal component of Eugenia haitiensis identified as 1,8-cineol. PMID- 20289465 TI - Studies in the quinoline series; 2-dihydroxystyryl-quinolines. PMID- 20289466 TI - The interaction of thiols and quinones. PMID- 20289467 TI - Phenyl-pyridylhydantoins. PMID- 20289468 TI - Isolation of l-arabinose. PMID- 20289469 TI - 2,3-Dimethoxy-6-chloro-9-phenanthrenecarboxylic acid. PMID- 20289470 TI - New compounds as plant growth regulators. PMID- 20289471 TI - Derivatives of fluorene. PMID- 20289472 TI - The rearrangement of the isomeric 1,2-dimethylamino-chloropropanes; the synthesis of amidone. PMID- 20289473 TI - 5(4)-Amino-4(5)-imidazolscarboxamide, a precursor of purines. PMID- 20289474 TI - Radioactive cholestenone. PMID- 20289475 TI - Nitrous oxide-oxygen anesthesia, for the general practitioner. PMID- 20289476 TI - Sterilization of hypodermic syringe. PMID- 20289477 TI - Nitrous oxide-oxygen pentothal anesthesia in dentistry. PMID- 20289478 TI - Patient's fears lessened by blindfold technic. PMID- 20289480 TI - Ethyl chloride in dental practice. PMID- 20289481 TI - Some considerations for anesthesia of the lower dental arch. PMID- 20289479 TI - A comparison of local and general anesthesia. PMID- 20289482 TI - Intraosseus injection technics for extraction of teeth and cavity preparation. PMID- 20289483 TI - Psychology essential to success in use of N20X0. PMID- 20289484 TI - The use of ethyl aminobenzoate. PMID- 20289485 TI - General anesthesia for problem children used in the treatment of extensive caries. PMID- 20289486 TI - Deaths under nitrous oxide-oxygen anesthesia not always caused by the anesthetic. PMID- 20289487 TI - Safety in general anesthesia for the cardiac patient by use of an oxygen-rich anesthetic mixture. PMID- 20289488 TI - GENERAL anesthesia used by 40 percent of dentists. PMID- 20289489 TI - Fundamental principles of full denture technic. PMID- 20289490 TI - Impression building recognizes the importance of mouth anatomy as the determining factor in denture form. PMID- 20289491 TI - Pre-extraction records necessary for the creation of esthetic full dentures. PMID- 20289492 TI - Proper vertical dimension for function, comfort and esthetics. PMID- 20289493 TI - Variations in the occlusal plane; their significance in denture prosthesis and use of the eye-ear plane. PMID- 20289494 TI - The relation of the dentist to the full denture patient. PMID- 20289495 TI - Occlusal corrections retain principles of natural function in artificial full dentures. PMID- 20289496 TI - The patient must be taught how to wear his new dentures. PMID- 20289497 TI - A preliminary report on a new technic for determining vertical dimension in full denture construction. PMID- 20289499 TI - Safe and adequate pressure for toothbrushing routines. PMID- 20289498 TI - Preventive dentistry and the general practitioner. PMID- 20289500 TI - Steps in making perfect inlay dies. PMID- 20289501 TI - Lectures on penicillin and the uses of penicillin in dental surgery. PMID- 20289502 TI - The advisability of extractions as a therapeutic aid in orthodontics; affirmative. PMID- 20289503 TI - The advisability of extractions as a therapeutic aid in orthodontics; affirmative. PMID- 20289504 TI - The advisability of extractions as a therapeutic aid in orthodontics; negative. PMID- 20289505 TI - The advisability of extractions as a therapeutic aid in orthodontics; negative. PMID- 20289506 TI - [Changes in the teeth of rats in experimental A and D avitaminosis]. PMID- 20289507 TI - [Prevention of dental caries by means of local fluorinization]. PMID- 20289508 TI - [Use of strontium chloride as a means of permanent anesthesia in enamel and dentin hyperesthesia]. PMID- 20289509 TI - [Therapy of pulpitis]. PMID- 20289510 TI - [Therapy of pulpitis]. PMID- 20289511 TI - [Changes in the antitoxin level in blood serum in surgical trauma]. PMID- 20289512 TI - [Use of sulfonamide in surgical dentistry]. PMID- 20289513 TI - [Treatment of trigeminal neuralgia by novocaine block]. PMID- 20289514 TI - [Significance of dental prosthesis for the course and results of facialmaxillary traumata]. PMID- 20289515 TI - [Treatment of some anomalies of occlusion]. PMID- 20289516 TI - [Teaching of surgical stomatology in dentistry schools]. PMID- 20289517 TI - [Reform of stomatological and odontological and odontological education]. PMID- 20289518 TI - [Reform of dental education]. PMID- 20289519 TI - [Results of the conference of facial-maxillary surgeons and orthopedists of base hospitals of RSFSR]. PMID- 20289520 TI - [Not Available]. PMID- 20289521 TI - [Not Available]. PMID- 20289522 TI - [Not Available]. PMID- 20289523 TI - [Not Available]. PMID- 20289524 TI - [Not Available]. PMID- 20289525 TI - [Not Available]. PMID- 20289526 TI - [Not Available]. PMID- 20289527 TI - Some experiences in a skin department of a prisoner-of-war camp hospital in Singapore, 1942-1945. PMID- 20289528 TI - Vitiligo in Brazil. PMID- 20289529 TI - Recurrent bullous eruption of the feet. PMID- 20289530 TI - Virus studies on cutaneous material; inoculation of the chick chorio-allantoic membrane with material from cutaneous lesions. PMID- 20289531 TI - Erythema multiforme exudativum (erythema bullosum malignans; pluriorificial type); personal observations of cases in Willard Parker Hospital for contagious diseases (1932-1946). PMID- 20289532 TI - Primary systematized amyloidosis with macroglossia; a syndrome related to Bence Jones proteinuria and myeloma. PMID- 20289533 TI - Impetigo contagiosa treated parenterally with penicillin-beeswax. PMID- 20289534 TI - Am improved method for diagnosing pemphigus. PMID- 20289535 TI - Dermatitis following paratoluylenediamine hair dye. PMID- 20289536 TI - Nutrition in maternal and child health programs. PMID- 20289537 TI - The nutritionist's interest in soils and agriculture. PMID- 20289538 TI - A physical symptom of value in the diagnosis of gallbladder pathology. PMID- 20289539 TI - Hypertrophic pyloric stenosis in the adult. PMID- 20289540 TI - A study of the mortality rate in a series of cholecystectomies. PMID- 20289541 TI - Management of the diabetic in acute infections and surgical emergencies. PMID- 20289542 TI - Cancer of the cecum; a review of the clinical features. PMID- 20289543 TI - An evaluation of some antacid and antipeptic agents in the prevention of gastric ulceration in the rat. PMID- 20289544 TI - The value of gastroscopy as a diagnostic aid in gastric lesions. PMID- 20289545 TI - Pruritus ani; a review of oral therapy. PMID- 20289546 TI - Psychotherapeutic methods in gastroenterology. PMID- 20289547 TI - Symposium on gallbladder disease. PMID- 20289548 TI - Surgical aspects of cholecystitis. PMID- 20289549 TI - Chronic biliary tract disease. PMID- 20289550 TI - Local sulphan ilaminotherapy in chronic thromboulcerative colitis by means of single or double colonic tube. PMID- 20289551 TI - Unusual (benign) hematemesis; gastric telangiectatic dysplasia; Rendu-Osler Weber's disease (Goldstein's hematemesis). PMID- 20289552 TI - Exaggeration phenomena as evidences of the allergic mechanism. PMID- 20289553 TI - Medico-legal aspects of civilian air-raid casualties. PMID- 20289554 TI - Damages for shock. PMID- 20289555 TI - Damages for shock; the medical aspect. PMID- 20289556 TI - The supernatural in the law courts with special reference to the Witchcraft Act, 1735. PMID- 20289557 TI - Tuberculosis and the law. PMID- 20289558 TI - Consummation of marriage and the law. PMID- 20289559 TI - Genetic differences in fatal audiogenic seizures between two inbred strains of house mice. PMID- 20289560 TI - The missing forearm muscle; a case of non-familial bilateral absence of the palmaris longus muscle in man. PMID- 20289561 TI - Some experiments with Melittobia and other wasps. PMID- 20289562 TI - Cytology of evolution and evolution of cytology. PMID- 20289563 TI - Cattle breeding in India; the development of milk production in two Indian breeds of cattle. PMID- 20289564 TI - [Basic problems of theoretical and practical obstetrics and gynecology in the postwar period]. PMID- 20289565 TI - [Development of innervation of the human ovary]. PMID- 20289566 TI - Opyt primeneniia sinestrola, stil'bestrola i dipropionata stil'bestrola v klinike. [Experiment with the use of synestrol, stilbestrol and dipropionate stilbestrol in the clinic]. PMID- 20289567 TI - [[On the role of pituicrinelike substances in etiology of prematurity]. PMID- 20289568 TI - [Content of prolane in the female urine in early pregnancy and after its interruption]. PMID- 20289569 TI - [Hormone composition of the liquor amnii]. PMID- 20289570 TI - [Folliculin therapy in disturbances of inversion of the uterus after parturition]. PMID- 20289571 TI - [Effect of lengthy periods of administration of estrogen on the thymus gland of the female rabbit]. PMID- 20289572 TI - [Blood transfusion in the control of acute anemia in obstetrics]. PMID- 20289573 TI - Endocrine allergy; clinical reactions to allergy to endogenous hormones and their treatment. PMID- 20289574 TI - The use of radiology in predicting difficult labour. PMID- 20289575 TI - Head flexion in forceps technique. PMID- 20289576 TI - A preliminary report on the pelvic brim index. PMID- 20289577 TI - The technique of the lower segment caesarean section. PMID- 20289578 TI - Fibroids in pregnancy (an analysis of 122 cases treated in University College Hospital, London, from 1934 to 1945). PMID- 20289579 TI - A statistical study on the effects of exercises on childbearing. PMID- 20289580 TI - Timing of endometrial biopsy. PMID- 20289581 TI - Coarctation of the aorta in association with pregnancy (a review of the literature with description of a case). PMID- 20289582 TI - A case of intersexuality; a clinical and hormonal study. PMID- 20289583 TI - A survey of gynaecological surgery. PMID- 20289584 TI - What is a physician's duty to society? PMID- 20289585 TI - Psychological aspects of jealousy. PMID- 20289586 TI - Effective treatment of bronchial asthma. PMID- 20289587 TI - New approaches to understanding the alcoholic. PMID- 20289588 TI - New approaches to understanding the alcoholic; the thematic apperception test. PMID- 20289589 TI - New approaches to understanding of alcoholic; the Rorschach analysis. PMID- 20289590 TI - Confessions of a drunkard. PMID- 20289591 TI - The work efficiency of the disabled; an analysis of the available reports on the job efficiency of physically disabled workers in industry. PMID- 20289592 TI - Case records are for use. PMID- 20289593 TI - Arthritis. PMID- 20289594 TI - Do we really understand a child who has cerebral palsy? PMID- 20289595 TI - Employment of persons with certain physical and neuropsychiatric impairments; aspects of rehabilitation and employment related to administration of workmen's compensation laws. PMID- 20289596 TI - Analytic methods in diagnosis. PMID- 20289597 TI - Rehabilitation of the limbless; a joint surgical and psychologic study. PMID- 20289599 TI - Industrial injuries of the back. PMID- 20289598 TI - Fitting the service to the plant. PMID- 20289600 TI - Administrative uses of statistical data in development of industrial hygiene programs. PMID- 20289601 TI - Industrial exposure to lead. PMID- 20289602 TI - Chemotherapy of leprosy. PMID- 20289603 TI - Injury of nerve elements of the tongue root in lepromatous leprosy. PMID- 20289604 TI - A study of the bacilli in tissue cultures of lepromata in serum media. PMID- 20289605 TI - The fate of leprosy bacilli in fibroblasts cultivated from macular and tuberculoid lesions. PMID- 20289606 TI - The fate of leprosy bacilli in fibroblasts cultivated from lepromatous lesions. PMID- 20289607 TI - The influence of carbon particles on the development of rat leprosy. PMID- 20289608 TI - The question of free bacillary growth in the plasma surrounding lepromatous explants during tissue cultivation. PMID- 20289609 TI - Attempts to infect chick embryos and chick tissue cultures with bacilli from human lepromatous lesions. PMID- 20289610 TI - Report of Subcommittee on Classification. PMID- 20289611 TI - Quantitative aspects of benzoyl glucuronate formation in normal individuals and in patients with liver disorders. PMID- 20289612 TI - Excretion of benzoy; glucuronate as a test of liver function. PMID- 20289613 TI - A note on studies of hemolysis in paroxysmal (cold) hemoglobinuria. PMID- 20289614 TI - Bacillus pyocyaneus infections; a review, report of cases and discussion of newer therapy including streptomycin. PMID- 20289615 TI - Clinical and laboratory diagnostic criteria of rheumatic fever in children. PMID- 20289616 TI - The nephrotic syndrome. PMID- 20289617 TI - Coronary artery disease. PMID- 20289618 TI - Subcutaneous emphysema in vomiting of pregnancy. PMID- 20289619 TI - Immunization against influenza. PMID- 20289620 TI - Management of patients with ureteral calculi. PMID- 20289621 TI - Poisoning with a preparation of iron, copper, and manganese. PMID- 20289622 TI - An outbreak of diphtheria in a highly immunized community. PMID- 20289623 TI - Faucial diphtheria among army personnel in Belgium, 1945; an analysis of 122 cases. PMID- 20289624 TI - Penicillin in the treatment of diphtheria. PMID- 20289625 TI - A case of mesenteric thrombosis complicating multiple wounds; recovery following massive resection. PMID- 20289626 TI - A case of dislocation of the metatarso-tarsal joints. PMID- 20289627 TI - Arsenical encephalopathy. PMID- 20289628 TI - Use of penicillin pastilles. PMID- 20289629 TI - Delayed reaction to penicillin. PMID- 20289630 TI - Cerebral malaria in Great Britain. PMID- 20289631 TI - Retrodisplaced gravid uterus. PMID- 20289632 TI - CORNOCK case, an unusually striking and complete instance of conflict of medical evidence. PMID- 20289633 TI - Renal oedema. PMID- 20289634 TI - Causes, theories, classification of cancer. PMID- 20289635 TI - Blood transfusion. PMID- 20289636 TI - Causes, theories, classification of cancer. PMID- 20289637 TI - Blood transfusion; shock. PMID- 20289638 TI - Undulant fever. PMID- 20289639 TI - Elective perineorrhaphy in the delivery room. PMID- 20289640 TI - Carcinoma of the stomach. PMID- 20289641 TI - What can the internist do to get more early cases of carcinoma of the stomach to the surgeon? PMID- 20289642 TI - What does gastroscopy offer in the early diagnosis of cancer of the stomach? PMID- 20289643 TI - Problems in the X-ray diagnosis of early cancer. PMID- 20289644 TI - Recent advances in surgical treatment of cancer of the upper end of the stomach. PMID- 20289645 TI - Radical surgical treatment of gastric cancer. PMID- 20289647 TI - Physiological basis for the treatment of intractable asthma. PMID- 20289646 TI - Use of the thymol turbidity test as an aid in diagnosis of dysfunctions of the liver. PMID- 20289648 TI - Management of patients with various types of goiter. PMID- 20289649 TI - AEROSOL therapy. PMID- 20289650 TI - [Generalized peritonitis due to perforation of a Meckel's diverticulum incarcerated in a right femoral hernia]. PMID- 20289651 TI - A rapid method for the assay of penicillin. PMID- 20289652 TI - A casein digest medium for toxin production by Clostridium. PMID- 20289653 TI - Yield of botulinum toxin in concentrated media. PMID- 20289654 TI - Anophelism and climate in relation to malaria in Manitoba. PMID- 20289655 TI - The ambulatory diabetic and the family doctor. PMID- 20289656 TI - Lymphadenopathy in association with thiouracil therapy. PMID- 20289657 TI - [Generalized hematogenous tuberculous infection involving lungs, peritoneum, liver, spleen and possibly the kidneys and pericardium]. PMID- 20289658 TI - The kidney and kidney function tests; the urea clearance test. PMID- 20289659 TI - The operation of Public Law 725, the Hospital Survey and Construction Act. PMID- 20289660 TI - Modern influences in medical practice. PMID- 20289661 TI - Present status of streptomycin in the treatment of tuberculosis. PMID- 20289662 TI - Common anal and rectal problems. PMID- 20289663 TI - The clinical use of fluorescein. PMID- 20289664 TI - Soft tissue sarcoma; ten years survival following roentgen ray therapy. PMID- 20289665 TI - The diagnostic clinic. PMID- 20289666 TI - Voluntary medical prepayment plans as they apply to rural communities. PMID- 20289667 TI - [Not Available]. PMID- 20289668 TI - [Not Available]. PMID- 20289669 TI - [Not Available]. PMID- 20289670 TI - [Not Available]. PMID- 20289671 TI - [Not Available]. PMID- 20289672 TI - [Not Available]. PMID- 20289673 TI - [Not Available]. PMID- 20289674 TI - [Not Available]. PMID- 20289675 TI - [Not Available]. PMID- 20289676 TI - [Not Available]. PMID- 20289677 TI - [Not Available]. PMID- 20289678 TI - [Not Available]. PMID- 20289679 TI - [Not Available]. PMID- 20289681 TI - [Not Available]. PMID- 20289680 TI - [Not Available]. PMID- 20289682 TI - [Not Available]. PMID- 20289683 TI - [Not Available]. PMID- 20289684 TI - [Not Available]. PMID- 20289685 TI - [Not Available]. PMID- 20289686 TI - [Not Available]. PMID- 20289687 TI - [Not Available]. PMID- 20289688 TI - [Not Available]. PMID- 20289689 TI - [Not Available]. PMID- 20289690 TI - [Not Available]. PMID- 20289691 TI - [Not Available]. PMID- 20289692 TI - [Not Available]. PMID- 20289693 TI - [Not Available]. PMID- 20289694 TI - [Not Available]. PMID- 20289695 TI - [Not Available]. PMID- 20289696 TI - [Not Available]. PMID- 20289697 TI - [Not Available]. PMID- 20289698 TI - [Not Available]. PMID- 20289699 TI - [Not Available]. PMID- 20289700 TI - [Not Available]. PMID- 20289701 TI - [Not Available]. PMID- 20289702 TI - [Not Available]. PMID- 20289703 TI - [Not Available]. PMID- 20289705 TI - [Not Available]. PMID- 20289704 TI - [Not Available]. PMID- 20289706 TI - [Not Available]. PMID- 20289707 TI - [Not Available]. PMID- 20289708 TI - [Not Available]. PMID- 20289709 TI - [Not Available]. PMID- 20289711 TI - [Not Available]. PMID- 20289710 TI - [Not Available]. PMID- 20289712 TI - [Not Available]. PMID- 20289713 TI - [Not Available]. PMID- 20289714 TI - [Not Available]. PMID- 20289715 TI - [Not Available]. PMID- 20289716 TI - [Not Available]. PMID- 20289717 TI - [Not Available]. PMID- 20289718 TI - [Not Available]. PMID- 20289719 TI - [Not Available]. PMID- 20289720 TI - [Not Available]. PMID- 20289721 TI - [Not Available]. PMID- 20289722 TI - [Not Available]. PMID- 20289723 TI - [Not Available]. PMID- 20289724 TI - [Not Available]. PMID- 20289725 TI - [Not Available]. PMID- 20289726 TI - [Not Available]. PMID- 20289727 TI - [Not Available]. PMID- 20289728 TI - [Not Available]. PMID- 20289729 TI - [Not Available]. PMID- 20289730 TI - [Not Available]. PMID- 20289731 TI - [Not Available]. PMID- 20289732 TI - [Not Available]. PMID- 20289733 TI - Medicine in Soviet Russia. PMID- 20289734 TI - The study of antimalarials and antimalarial activity in the human malarias. PMID- 20289735 TI - Physiopathology and surgical treatment of congenital cardiovascular defects. PMID- 20289736 TI - The chemical evolution of vision. PMID- 20289738 TI - Radioactivity and Nagasaki. PMID- 20289737 TI - Experiments with bacterial viruses (bacteriophages). PMID- 20289739 TI - Biological antagonisms between metabolically important compounds and their structural analogs. PMID- 20289740 TI - Inter-relationships between gonadotrophic and sex hormones. PMID- 20289741 TI - Enzymatic reactions in carbohydrate metabolism. PMID- 20289742 TI - Studies on the cultivation of the aetiological agent of rabies in vitro and its nature. PMID- 20289743 TI - Studies on antirabic immunization with culture vaccine. PMID- 20289744 TI - Action of penicillin on Mycobacterium leprae muris. PMID- 20289745 TI - Serological studies in a case of acute haemorrhagic jaundice. PMID- 20289747 TI - Pharmacological action of an active constituent isolated from Vanda roxburghii R. Br. PMID- 20289746 TI - Complement-fixation reaction between serum-protein and its antibody for medico legal purposes; and associated immunological considerations. PMID- 20289748 TI - The level of fat intake and the composition of serum lipoids. PMID- 20289749 TI - Studies in experimental rickets; the changes in the ionic products of calcium phosphates and the serum alkaline phosphatase with the onset, progress and healing of rickets. PMID- 20289750 TI - The effect of different diets and of iron medication on the nutritional anaemia of Indian army recruits. PMID- 20289751 TI - Vitamin B1 (thiamin) content of Indian foodstuffs. PMID- 20289752 TI - Toxic effects in guinea-pigs of diets containing large proportions on Lathyrus sativus. PMID- 20289754 TI - Experiments on the transmission of human schistosomiasis in India. PMID- 20289753 TI - Studies on some dextrorotatory hydrocupreidine derivatives; comparative spermicidal effects on cavy (guinea-pig) sperms. PMID- 20289755 TI - A note on the action of heparin on Russell's viper venom. PMID- 20289756 TI - A general survey of leprosy. PMID- 20289758 TI - Treatment of the diabetic patient. PMID- 20289757 TI - Management of asthmatic cases. PMID- 20289759 TI - An interesting case of monster weighing 18 pounds. PMID- 20289760 TI - Current problems in medical education. PMID- 20289761 TI - Hospitals and the health of the people. PMID- 20289762 TI - Long term illness in modern society. PMID- 20289763 TI - Responsibilities of a medical school to a community. PMID- 20289764 TI - Peptic ulcer in the aged. PMID- 20289765 TI - Asthma in children; treatment with the radium nasopharygeal applicator. PMID- 20289766 TI - Fatal allergic reaction due to influenza vaccine. PMID- 20289767 TI - Hospital service in the United States; twenty-sixth annual presentation of hospital data by the Council on Medical Education and Hospitals of the American Medical American Medical Association. PMID- 20289768 TI - MALPRACTICE: physician's liability after payment of compensation award to employee [Idaho, 1946]. PMID- 20289769 TI - Prostatectomy. PMID- 20289770 TI - The granulating surface. PMID- 20289771 TI - Sarcopticides. PMID- 20289772 TI - An unusual case of metrorrhagia at puberty in an unmarried girl. PMID- 20289773 TI - Selection of medical students for the Christian Medical College. PMID- 20289774 TI - The treatment of burns. PMID- 20289775 TI - Cardiospasm. PMID- 20289776 TI - Penicillin therapy in a case of facial carbuncle. PMID- 20289777 TI - The Christian Medical College, Vellore. PMID- 20289778 TI - The present outlook on pathology. PMID- 20289779 TI - Discussion of some relationships between endocrinology and legal medicine. PMID- 20289780 TI - Cancer control agencies. PMID- 20289781 TI - The complications of craniocerebral injuries. PMID- 20289782 TI - The significance of changes in the female breast. PMID- 20289783 TI - Leukoplakia and carcinoma of the vulva. PMID- 20289785 TI - American medicine looks to the future. PMID- 20289784 TI - The psychiatric trend in medicine. PMID- 20289786 TI - The nurse shortage. PMID- 20289787 TI - The action of choline on the blood lipid fractions in cirrhosis of the liver, diabetes mellitus and related conditions of disturbed fat metabolism. PMID- 20289788 TI - Punch biopsy of the liver. PMID- 20289789 TI - Vaginal smear in the diagnosis of gynecologic cancer. PMID- 20289790 TI - Physiologic basis for therapeutic trends in neuromuscular dysfunction. PMID- 20289791 TI - The diagnosis and treatment of congenital syphilis. PMID- 20289792 TI - Psychiatric needs of general hospitals. PMID- 20289793 TI - Intracerebellar hemorrhage; a complication in the course of cerebral arteriosclerosis. PMID- 20289794 TI - Blood transfusion studies; the relationship of hemoglobinemia and of the pH of the urine to renal damage produced by injection of hemoglobin solutions into dogs. PMID- 20289795 TI - The treatment of pernicious and related anemias with synthetic folic acid; observations on the maintenance of a normal hematologic status and on the occurrence of combined system disease at the end of one year. PMID- 20289796 TI - Studies of the distribution of intravenously administered colloidal sols of manganese dioxide and gold in human beings and dogs using radioactive isotopes. PMID- 20289797 TI - Effect of pregnancy on the complement of guinea pigs. PMID- 20289798 TI - Toxicity studies of alpha (4-hydroxy-3,5-diiodo-benzyl-n-butyric acid) and alpha (4-hydroxy-3,5-diiodo-benzyl-n-caproic acid): compounds proposed as gall bladder contrast agents. PMID- 20289799 TI - The microcolorimetric estimation of plasma proteins. PMID- 20289800 TI - A pulsating perfusion apparatus. PMID- 20289801 TI - Evaluation of vasomotor tone in animals and man by means of the tetraethylammonium ion. PMID- 20289802 TI - The influence of various diuretics on the urinary sodium of normal pregnant women. PMID- 20289803 TI - The mercurial diuretics; a comparison of acute cardiac toxicity in animals and the effect of ascorbic acid on detoxification in their intravenous administration. PMID- 20289804 TI - The serum protein fraction responsible for the thymol turbidity test. PMID- 20289805 TI - Biopsy of liver in patients with active brucellosis: description of hepatic lesions. PMID- 20289806 TI - Studies in convalescence following herniorrhaphy; the effect of diet, supplements, and ambulation on metabolic changes and on the performance of patients as measured by tests of cardiovascular efficiency and muscular fitness. PMID- 20289807 TI - Relation between structural and functional alterations of the liver. PMID- 20289808 TI - Hepatitis without jaundice in infections mononucleosis. PMID- 20289809 TI - The experimental production of jaundice of the direct-reacting type by the injection of a preparation of direct-reacting bilirubin. PMID- 20289810 TI - The effect of methionine upon the urinary nitrogen in human beings at normal and low levels of protein intake. PMID- 20289811 TI - Ulcer of the leg due to arteriolosclerosis and ischemia occurring in the presence of hypertensive disease (hypertensive-ischemic ulcers); a preliminary report. PMID- 20289812 TI - Aortic stenosis; an analysis of 106 proved cases. PMID- 20289813 TI - An analysis of immediate mortality in 572 cases of recent myocardial infarction. PMID- 20289814 TI - Present status of the therapy of experimental renal hypertension. PMID- 20289815 TI - The results of surgery in patent ductus arteriosus. PMID- 20289816 TI - Pulmonary arteriovenous fistula with secondary polycythemia occurring in two brothers; cure by pneumonectomy. PMID- 20289817 TI - The diagnostic value of electrocardiographic patterns based on an assay of 261 additional autopsied cases. PMID- 20289818 TI - Antitularense serum; correlation between protective capacity for white rats and precipitable antibody content. PMID- 20289819 TI - Evaluation of the treatment of primary pneumococcic pneumonia. PMID- 20289820 TI - A study of the action of beta-dimethylaminoethyl benzhydryl ether hydrochloride (benadryl) in the skin of human beings. PMID- 20289821 TI - The occurrence of combined system disease in persons with pernicious anemia during treatment with the Lactobacillus casei factor (folic acid). PMID- 20289822 TI - Nonutilization of conjugated folic acid in pernicious anemia. PMID- 20289823 TI - Further studies on the utilization of pteroyl hexaglutamyl glutamic acid (vitamin Bc conjugate) in pernicious anemia. PMID- 20289824 TI - Rutin in purpura. PMID- 20289825 TI - The effect of total body X-irradiation on a pre-existing induced anemia. PMID- 20289826 TI - On the relation of calcium to the activation of prothrombin and its significance in dicumarol poisoning. PMID- 20289827 TI - Morphology of bone marrow; imprint and histologic preparation of aspirated sternal marrow units. PMID- 20289828 TI - The effect of radiation therapy on the nocturnal gastric secretion in patients with duodenal ulcer. PMID- 20289829 TI - The measurement of human gastric function. PMID- 20289830 TI - The effect of enterogastrone on fasting gastric secretion and motility in patients with duodenal ulcers. PMID- 20289832 TI - The physician and social responsibilities. PMID- 20289831 TI - Effects of alloxan upon the human pancreas. PMID- 20289833 TI - Treatment of menincococcic meningitis. PMID- 20289834 TI - Scabies among the well-washed. PMID- 20289835 TI - Maternal mortality; some aspects of its preventability. PMID- 20289836 TI - A successful financial plan for group practice. PMID- 20289837 TI - The management of strabismus. PMID- 20289838 TI - Hypertensive heart disease. PMID- 20289840 TI - Varicose veins; observations on management and mismanagement. PMID- 20289839 TI - Some clinical disturbances of the endocrine glands. PMID- 20289841 TI - Local tonsillectomy. PMID- 20289842 TI - New concepts of the causes of asthma. PMID- 20289843 TI - Factors influencing nausea and vomiting following intravenous amino acid administration. PMID- 20289844 TI - Development of asymmetry in the morphogenesis of the amphibian digestive tract. PMID- 20289845 TI - Experimental studies of malaria in cold-blooded animals. PMID- 20289846 TI - Symposium on fractures. PMID- 20289847 TI - Colles fracture. PMID- 20289848 TI - Fractures about the elbow joint. PMID- 20289849 TI - Fractures of the hip. PMID- 20289850 TI - Treatment of simple fractures of the ankle. PMID- 20289851 TI - Perforated diverticulum of the sigmoid. PMID- 20289852 TI - The ruptured intervertebral disc syndrome; is it an orthopedic or neurosurgical problem? PMID- 20289853 TI - Unilateral ruptures of the lower cervical intervertebral discs. PMID- 20289854 TI - Diagnostic considerations in neurology and psychiatry. PMID- 20289855 TI - Inflammatory diseases of the small intestine. PMID- 20289856 TI - Ophthalmoscopy as a diagnostic and prognostic aid. PMID- 20289857 TI - Some observations on deafness and its treatment. PMID- 20289859 TI - Studies on the testes of hypogonadal men. PMID- 20289858 TI - Treatment of chronic osteomyelitis. PMID- 20289860 TI - Clinical applications of the male sex hormone. PMID- 20289861 TI - The diagnosis and treatment of cortical disease. PMID- 20289862 TI - Present limitations of pituitary therapy. PMID- 20289863 TI - Use of estrogens and progesterone. PMID- 20289864 TI - Ante partum bleeding. PMID- 20289865 TI - Post operative care of the surgical patient. PMID- 20289866 TI - Recent advances in surgery. PMID- 20289867 TI - Salt intoxication; accidental ingestion of a large amount of sodium chloride; report of a case with autopsy of a two year old infant. PMID- 20289868 TI - The kidney and hypertension. PMID- 20289869 TI - [Early papillary carcinoma of bladder]. PMID- 20289870 TI - The chronic sick in hospital; a psychiatric approach. PMID- 20289871 TI - Treatment of anuria following intravascular haemolysis. PMID- 20289872 TI - Palpable epitrochlear glands; incidence and relation to syphilis. PMID- 20289873 TI - Revaccination in adults. PMID- 20289874 TI - Sexual inversion; an ethical study. PMID- 20289875 TI - Anterior bone graft for recurrent shoulder dislocation. PMID- 20289876 TI - General practice tomorrow. PMID- 20289878 TI - MICROFILM projectors. PMID- 20289877 TI - Lactation. PMID- 20289879 TI - The student nurse. PMID- 20289880 TI - Lesser circulation of the kidney. PMID- 20289881 TI - Death in the fireplace [risks of unscreened fires]. PMID- 20289882 TI - Compression of median nerve in carpal tunnel. PMID- 20289883 TI - Revision of the anatomical curriculum at Birmingham University. PMID- 20289884 TI - Ascorbic-acid metabolism of Bantu soldiers. PMID- 20289885 TI - Estimation of penicillin in serum; use of glucose, phenol red, and serum water. PMID- 20289886 TI - Observations on fibrinolysis; experimental activity produced by exercise or adrenaline. PMID- 20289887 TI - Ankylosing spondylitis; review of 25 cases. PMID- 20289888 TI - Stabilisation of penicillin solutions with sodium citrate. PMID- 20289889 TI - Generalised skin sensitivity following local application of acriflavine; report of a case. PMID- 20289890 TI - A group practice. PMID- 20289891 TI - Age and sex distribution of diphtheria in Oldenburg, Germany. PMID- 20289892 TI - The student nurse. PMID- 20289893 TI - Treatment of tuberculosis. PMID- 20289894 TI - Of not smoking. PMID- 20289895 TI - The medical school. PMID- 20289896 TI - [Not Available]. PMID- 20289897 TI - [Not Available]. PMID- 20289898 TI - [Not Available]. PMID- 20289899 TI - [Not Available]. PMID- 20289900 TI - [Not Available]. PMID- 20289901 TI - [Not Available]. PMID- 20289902 TI - The management of urinary infections. PMID- 20289903 TI - High blood pressure. PMID- 20289904 TI - Some observations on vagotomy for peptic ulcer with a discussion of three selected cases. PMID- 20289905 TI - The indications and value of X-ray examination in obstetrics. PMID- 20289906 TI - Ovarian tumor in childhood; report of a case. PMID- 20289907 TI - LARYNGEAL tuberculosis. PMID- 20289908 TI - Post-tonsillectomy lung abscess. PMID- 20289909 TI - An unusual gastric lesion. PMID- 20289910 TI - Can we win the peace through science? PMID- 20289911 TI - Experience with a series of 450 cases of pilonidal disease at a naval hospital. PMID- 20289912 TI - Migraine headache; treatment of 51 patients with dihydroergotamine. PMID- 20289913 TI - The treatment of gonorrhea with streptomycin; a preliminary report with cure of four cases. PMID- 20289914 TI - The role of the pediatrician in poliomyelitis. PMID- 20289916 TI - WHAT prepay plans give and get. PMID- 20289915 TI - The goal of rehabilitation. PMID- 20289917 TI - Calculus disease of the urinary tract. PMID- 20289918 TI - Psychiatric aspects of the menopause. PMID- 20289919 TI - Vomiting in infancy. PMID- 20289920 TI - The diagnosis and treatment of acute and chronic sinusitis. PMID- 20289921 TI - [Pernicious anemia]. PMID- 20289922 TI - The functions of a general hospital. PMID- 20289923 TI - The surgical management of incomplete abortions. PMID- 20289924 TI - Melanoma. PMID- 20289925 TI - A new concept in cardiology. PMID- 20289926 TI - Obesity and its management; a survey of 671 patients. PMID- 20289927 TI - Acute maxillary sinusitis. PMID- 20289928 TI - Vitamin E in heart disease; the hypertensive heart. PMID- 20289929 TI - Venereal disease rate reduction. PMID- 20289930 TI - Minds and movies. PMID- 20289931 TI - Problems in gastric surgery. PMID- 20289932 TI - Phlegmonous cecitis with a case report. PMID- 20289933 TI - Mesentric vascular occlusion. PMID- 20289934 TI - A case of oedema of the legs. PMID- 20289935 TI - Sir Robert Sibbald. PMID- 20289936 TI - Domiciliary obstetrics; the physiology of the puerperium. PMID- 20289937 TI - Archibald Pitcairne. PMID- 20289938 TI - Objections to socialized medicine. PMID- 20289939 TI - Acute intussusception in infancy and childhood; report of 58 cases. PMID- 20289940 TI - Financing the establishment of a small hospital. PMID- 20289942 TI - Duodenal diverticulum. PMID- 20289941 TI - A short commentary on the history of the circulation; modern addenda. PMID- 20289943 TI - Office proctology. PMID- 20289944 TI - Getting the most from a pathologist. PMID- 20289945 TI - Kimmelstiel-Wilson syndrome. PMID- 20289947 TI - Adenocarcinoma of the sweat glands with metastases. PMID- 20289946 TI - [Pedunculated rhabdomyosarcoma of the right interauricular septum]. PMID- 20289948 TI - Periarteritis nodosa; treatment with penicillin. PMID- 20289949 TI - The treatment of hysteria by narco-hypnosis. PMID- 20289950 TI - Surgical management of chronic fistulas of the rectum following penetrating wounds. PMID- 20289951 TI - Pulmonary decortication for infected organized hemothorax; report of a case. PMID- 20289952 TI - Criteria for choledochostomy tube removal. PMID- 20289953 TI - Massive gastric hemorrhage due to hemorrhagic gastritis necessitating gastric resection; case report. PMID- 20289954 TI - The clinical problems of the Rh factor in obstetrics. PMID- 20289955 TI - Important considerations in the management of fractures of the hand and the fingers. PMID- 20289956 TI - A report on the use of cotton as suture material. PMID- 20289957 TI - Causes of increased intraocular tension. PMID- 20289958 TI - Present day economic trends in medicine. PMID- 20289959 TI - Bronchoscopy and esophagoscopy in the diagnosis and treatment of chest pathology. PMID- 20289960 TI - Three cases of meningitis treated with penicillin. PMID- 20289961 TI - A critical review of health and health plans in the United States. PMID- 20289962 TI - Radiation treatment of warts. PMID- 20289963 TI - Geriatrics and the general practitioner. PMID- 20289964 TI - Thrombosis and its possible prevention. PMID- 20289965 TI - Pulmonary tuberculosis, early and differential diagnosis. PMID- 20289966 TI - The incidence of pathologically significant tuberculosis in routine necropsies in private and public general hospitals. PMID- 20289967 TI - The use of the bronchoscope in the diseases of the chest. PMID- 20289968 TI - Surgery in diseases of the chest. PMID- 20289969 TI - Maternal mortality in Brooklyn for 1945. PMID- 20289970 TI - Clinical use of penicillin in otolaryngology. PMID- 20289971 TI - Management of renal lithiasis. PMID- 20289972 TI - Parenteral nitrogen therapy in surgical nutrition including the use of a mixture of pure amino acids. PMID- 20289973 TI - Acute exacerbation of a chronic cor pulmonale. PMID- 20289974 TI - History of the New Zealand medical services in the war 1939-1945. PMID- 20289975 TI - Curare in anaesthesia. PMID- 20289976 TI - The control of tuberculosis in New Zealand. PMID- 20289977 TI - Some social factors in relation to tuberculosis. PMID- 20289978 TI - MANTOUX testing of nurses; report on standardised technique and interpretation. PMID- 20289979 TI - Ligation of the patent ductus arteriosus complicated by subacute bacterial endarteritis; case report. PMID- 20289980 TI - Benign lymphocytic meningitis; a report of two cases with reduction of chlorides in the cerebrospinal fluid. PMID- 20289981 TI - The intervertebral disc and low backache. PMID- 20289982 TI - Widespread surgical emphysema. PMID- 20289983 TI - Congenital malformation of the vagina. PMID- 20289984 TI - Blood substitutes and parenteral fluids; derivation and their relative values. PMID- 20289985 TI - The use and abuse of blood substitutes and parenteral fluids in general surgery. PMID- 20289986 TI - Blood substitutes and parenteral fluids in gynecology and obstetrics. PMID- 20289987 TI - Blood substitutes and parenteral fluids. PMID- 20289988 TI - Blood substitutes and parenteral fluids; use and abuse in internal medicine. PMID- 20289989 TI - The diagnosis and management of tinea capitis. PMID- 20289990 TI - The management of myocardial infarction. PMID- 20289991 TI - The treatment of congestive heart failure. PMID- 20289992 TI - Treatment of cardiac failure with the rice diet; history of a patient with myocardial aneurysm. PMID- 20289993 TI - A basis for the treatment of rheumatoid arthritis. PMID- 20289994 TI - The treatment of psychogenic headaches. PMID- 20289995 TI - The recognition and management of subarachnoid hemorrhage. PMID- 20289996 TI - The treatment of the chronic convulsive disorders. PMID- 20289997 TI - Modern concepts of the treatment of peptic ulcer. PMID- 20289998 TI - The treatment of anemia. PMID- 20289999 TI - The treatment of diabetic acidosis. PMID- 20290000 TI - The prescribing of diets in the treatment of diabetes mellitus. PMID- 20290001 TI - Some common forms of overtreatment. PMID- 20290002 TI - The significance of hypersensitivity in diagnostic tests and in the therapy of infectious diseases. PMID- 20290003 TI - Desensitization in the treatment of asthma. PMID- 20290004 TI - Penicillin aerosol therapy. PMID- 20290005 TI - New horizons in drug therapy. PMID- 20290006 TI - Induction of premature labor. PMID- 20290007 TI - The sequelae of closed head injuries; evaluation, treatment and prognostic considerations. PMID- 20290008 TI - Some thoughts on abortion. PMID- 20290009 TI - Aerosol penicillin in upper respiratory infections in general practice. PMID- 20290010 TI - Von Jaksch's syndrome in congenital syphilis. PMID- 20290011 TI - The penicillin treatment of gonorrhea in the female; a study of the time-dose ratio. PMID- 20290012 TI - Recent research in allergy. PMID- 20290013 TI - The present status of cancer research. PMID- 20290014 TI - Subarachnoid hemorrhage. PMID- 20290015 TI - The relationship of gynecology to obstetrics. PMID- 20290016 TI - Evaluation of the treatment of primary penumococcic pneumonia. PMID- 20290017 TI - The prevention of rheumatic fever in children by the use of sulfonamides. PMID- 20290018 TI - THE BISHOP OF LONDON. Morals and sex; a Christian view. PMID- 20290019 TI - The role of marriage guidance. PMID- 20290020 TI - The problem of sterility; its investigation and treatment. PMID- 20290021 TI - The causation and treatment of impotence. PMID- 20290022 TI - Disorders of sex as a manifestation of endocrine abnormalities. PMID- 20290023 TI - The adrenals in sex. PMID- 20290024 TI - The problems of adolescence. PMID- 20290025 TI - The child and sex. PMID- 20290026 TI - Prostitution. PMID- 20290027 TI - Sexual perversions and their treatment. PMID- 20290028 TI - Legal aspects of artificial insemination. PMID- 20290029 TI - Pain in disease of the nervous system. PMID- 20290030 TI - Anticoagulants. PMID- 20290031 TI - Psoriasis; etiology and treatment. PMID- 20290032 TI - Diuretics. PMID- 20290033 TI - Addison's disease, a diagnostic problem; report of a case. PMID- 20290034 TI - Heterotopic pancreatic tissue, clinically significant, in the gastric wall of a boy six years of age. PMID- 20290035 TI - Curare in the treatment of poliomyelitis. PMID- 20290036 TI - Recurring hematocolpometra associated with carcinoma treated by partial hysterectomy; report of case. PMID- 20290038 TI - Vasomotor rhinitis medicamentosa viewed histologically. PMID- 20290037 TI - Mycotic aneurysm of the posterior tibial artery complicating subacute bacterial endocarditis; antemortem diagnosis confirmed by instrumental means. PMID- 20290039 TI - Perforating ovarian cystic teratomas; report of an unusual case. PMID- 20290040 TI - Rehabilitation of the deafened. PMID- 20290041 TI - Methods of bringing and holding doctors in rural areas. PMID- 20290042 TI - Carcinoma of the jejunum. PMID- 20290043 TI - Congo red in myasthenia gravis. PMID- 20290044 TI - The pharmacology of a series of new sympatholytic agents. PMID- 20290045 TI - The roentgen examination of the sphenoidal fissures. PMID- 20290046 TI - Repairing bone defects in cranium and tibia. PMID- 20290047 TI - Technical considerations in adequate transurethral prostatic resection. PMID- 20290048 TI - Diverticulosis coli with coexisting carcinoma of the rectosigmoid; a report of two cases. PMID- 20290049 TI - Fractures of the pelvis; study of end results. PMID- 20290050 TI - Abortion treated conservatively; a 12-year study covering 3,739 cases. PMID- 20290051 TI - Some effects of posture on patients during and after operation. PMID- 20290052 TI - Present evaluation of the response of prostatic cancer to hormone therapy. PMID- 20290053 TI - Lack of response to insulin; report of a patient treated with five thousand units per twenty-four hours. PMID- 20290054 TI - Acute hepatitis in children; clinical features and laboratory tests. PMID- 20290055 TI - Narcosynthesis in civilian practice. PMID- 20290056 TI - The physician and the psoriatic. PMID- 20290057 TI - Malaria; practical aspects in management. PMID- 20290058 TI - A study to determine likely precursors of gastric cancer. PMID- 20290059 TI - Folic acid. PMID- 20290060 TI - The treatment for temporary renal insufficiency. PMID- 20290061 TI - Premature closure of the cranial sutures. PMID- 20290062 TI - Vitamin D2 in the treatment of cutaneous tuberculosis. PMID- 20290063 TI - Acute poliomyelitis in children. PMID- 20290064 TI - Moniliasis. PMID- 20290065 TI - Epidemiology of poliomyelitis, 1946, in Minnesota. PMID- 20290066 TI - The role of the out-patient department in medical education. PMID- 20290067 TI - Radiation therapy of pituitary tumors. PMID- 20290069 TI - Unilateral exophthalmos. PMID- 20290068 TI - Results of surgery and radiation for carcinoma of the breast with axillary metastasis. PMID- 20290070 TI - Intravenous infusion in surgical practice. PMID- 20290071 TI - A review of the lupus problem. PMID- 20290072 TI - THE cell theory in the history of biology. PMID- 20290073 TI - Medicine in Shakespearean drama. PMID- 20290074 TI - Government documents in medical bibliography. PMID- 20290075 TI - Medical service second to none. PMID- 20290077 TI - Occiput posterior and its treatment. PMID- 20290078 TI - Para-aminobenzoic acid in the treatment of Rocky Mountain spotted fever. PMID- 20290076 TI - The selection of an obstetric forceps to suit the case. PMID- 20290079 TI - Juvenile rheumatic fever. PMID- 20290080 TI - Dissimulation in schizophrenic psychoses. PMID- 20290081 TI - Do bony spurs cause pain? PMID- 20290082 TI - Renal neoplasms; a review of 48 cases. PMID- 20290083 TI - Herniation and exstrophy of the ileum in the newborn incidental to adherent Meckel's diverticulum in the umbilical area; case report. PMID- 20290084 TI - Preventive ophthalmology. PMID- 20290085 TI - Cooperation of medical profession in vocational rehabilitation program. PMID- 20290086 TI - [Not Available]. PMID- 20290087 TI - [Not Available]. PMID- 20290088 TI - [Not Available]. PMID- 20290089 TI - [Not Available]. PMID- 20290090 TI - [Not Available]. PMID- 20290091 TI - [Not Available]. PMID- 20290092 TI - [Not Available]. PMID- 20290093 TI - [Not Available]. PMID- 20290094 TI - [Not Available]. PMID- 20290096 TI - [Not Available]. PMID- 20290095 TI - [Not Available]. PMID- 20290098 TI - [Not Available]. PMID- 20290097 TI - [Not Available]. PMID- 20290099 TI - [Not Available]. PMID- 20290100 TI - [Not Available]. PMID- 20290101 TI - [Not Available]. PMID- 20290102 TI - [Not Available]. PMID- 20290103 TI - [Not Available]. PMID- 20290104 TI - [Not Available]. PMID- 20290105 TI - [Not Available]. PMID- 20290106 TI - [Not Available]. PMID- 20290107 TI - [Not Available]. PMID- 20290108 TI - [Not Available]. PMID- 20290109 TI - [Not Available]. PMID- 20290110 TI - [Not Available]. PMID- 20290111 TI - [Not Available]. PMID- 20290112 TI - [Not Available]. PMID- 20290113 TI - [Not Available]. PMID- 20290114 TI - [Not Available]. PMID- 20290115 TI - [Not Available]. PMID- 20290116 TI - [Not Available]. PMID- 20290117 TI - [Not Available]. PMID- 20290118 TI - [Not Available]. PMID- 20290119 TI - [Not Available]. PMID- 20290120 TI - [Work among warblinded at B-base hospital]. PMID- 20290121 TI - [Amputation stumps of fingers and prostheses]. PMID- 20290122 TI - [On the problem of handling a foot prosthesis]. PMID- 20290123 TI - [Osteomyelitis in war stumps]. PMID- 20290124 TI - [Osteomyelitis in gunshot injuries of the foot]. PMID- 20290125 TI - [Balneotherapy of war injuries]. PMID- 20290126 TI - [Tibial osteoplasty in tissues known to be infected]. PMID- 20290127 TI - [Wounds of the penis]. PMID- 20290128 TI - [Use of the foreskin for flaps in reconstructive surgery]. PMID- 20290129 TI - [War phlegmon]. PMID- 20290130 TI - [Fate of traumatic hemorrhages]. PMID- 20290131 TI - [Mortality in somatic diseases according to materials of the Chkakov Base Hospital throughout the war]. PMID- 20290132 TI - [Brief analysis of the work of the hospital department of blood transfusion]. PMID- 20290133 TI - [News in X-ray therapy of skin diseases]. PMID- 20290134 TI - [Quantitative determination of albumin in urine]. PMID- 20290135 TI - [A stand for blood transfusion and intravenous administration of various solutions]. PMID- 20290137 TI - HOSPITAL mess. PMID- 20290136 TI - BACTERIOLOGY of dishwashing; laboratory examination of eating and drinking utensils. PMID- 20290138 TI - Adaptation of filtrable viruses to different host species and different tissues. PMID- 20290139 TI - Some of the medical accomplishments in New York, New Jersey, and Delaware during World War II with particular reference to Metropolitan New York. PMID- 20290140 TI - The evacuation of sick and non-effective wounded in amphibious warfare. PMID- 20290141 TI - Naval research in oral pathology. PMID- 20290142 TI - The effect of high altitude on oral tissues. PMID- 20290143 TI - The medical rehabilitation program of the Veterans Administration. PMID- 20290144 TI - Formation vertigo; oculovestibulo disorientation in formation flying. PMID- 20290145 TI - Nursing under fire. PMID- 20290146 TI - Relation, historical and surgical, of the expedition of the Army of Orient, in Egypt and in Syria [transl. Rose Alexander]. PMID- 20290147 TI - PRISONERS of war evacuated from Kyushu. PMID- 20290148 TI - TUBERCULOSIS since 1912. PMID- 20290149 TI - DISEASES of the nervous system. PMID- 20290150 TI - FACTORS influencing the incidence of tuberculosis. PMID- 20290151 TI - REACTIONS to typhoid prophylaxis. PMID- 20290152 TI - DENTAL care in the Navy. PMID- 20290153 TI - AMPUTEES in World War II. PMID- 20290154 TI - USE of graphic charts in medical statistics. PMID- 20290155 TI - DISEASES of the eye and adnexa. PMID- 20290156 TI - Thiamin in Manitoba vegetables. PMID- 20290157 TI - A variation of the termite Coptotermes lacteus Frogg, from New Zealand. PMID- 20290158 TI - Some minor constituents of pig back fat. PMID- 20290160 TI - Note on tyroglyphid mite species on cheese in New Zealand. PMID- 20290159 TI - Alkaloids of the leguminosae; alkaloids of Genista aethnensis DC. PMID- 20290161 TI - Developmental anatomy of seedling of Jatropha cordata. PMID- 20290162 TI - Consciousness in dream and in hypnotic state. PMID- 20290164 TI - The treatment of psychopaths and borderline patients. PMID- 20290163 TI - Otto Weininger and bisexuality; a psychoanalytic study. PMID- 20290165 TI - Psychotherapeutic value of books in the treatment and prevention of juvenile delinquency. PMID- 20290167 TI - The need for research in mental disease. PMID- 20290166 TI - A rare case of sadomasochism. PMID- 20290168 TI - Scientific capital and the dividends of applied science. PMID- 20290169 TI - Practical value of convulsive shock therapy research. PMID- 20290170 TI - The need for research in mental deficiency. PMID- 20290171 TI - The practical value of research in the psychoses of later life. PMID- 20290172 TI - Practical aspects of research in epilepsy. PMID- 20290173 TI - [FIFTY years of the scientific work of Victor Petrovich Osipov]. PMID- 20290174 TI - [Employment of clauses 1-9 of the statute concerning fitness for military service]. PMID- 20290175 TI - [Experimental investigations of mental operations after the method of restoration of deformed texts of patients with manic-depressive psychosis]. PMID- 20290176 TI - [Syndrome of hypopathy]. PMID- 20290177 TI - [Analysis of the mechanism of development of post-contusional conditions]. PMID- 20290178 TI - [Biological peculiarities in the blood of patients with manic-depressive psychosis during the maniacal and the depressive phases]. PMID- 20290179 TI - [Difficulties in diagnosis of purulent complications in penetrating injuries of the brain]. PMID- 20290180 TI - [Electroencephalography in Great Britain during the war]. PMID- 20290181 TI - [Functional asynapsia]. PMID- 20290182 TI - [Theory of eserine therapy in organic diseases of the central nervous system]. PMID- 20290183 TI - [Effect of eserine in syringomyelia]. PMID- 20290184 TI - [Eserine therapy in residual paralyses following tick encephalitis]. PMID- 20290185 TI - [Cutaneous vascular reactions in injuries of the peripheral nerves]. PMID- 20290186 TI - [Fifty years anniversary of Babin ski's symptom]. PMID- 20290187 TI - [Functional peculiarities of the cerebellum in the light of encephalography]. PMID- 20290188 TI - What do we psychiatric social workers think is the matter with us? PMID- 20290189 TI - Some considerations on the selection of patients for group treatment in a convalescent clinic. PMID- 20290191 TI - A psychiatric social casework orientation to therapy. PMID- 20290190 TI - The psychiatric social worker in a veterans service center. PMID- 20290192 TI - Current developments in case work in the family field as they relate to psychiatry. PMID- 20290193 TI - Ego strengths and therapy. PMID- 20290194 TI - [Not Available]. PMID- 20290195 TI - [Not Available]. PMID- 20290196 TI - [Not Available]. PMID- 20290197 TI - [Not Available]. PMID- 20290198 TI - [Not Available]. PMID- 20290199 TI - [Not Available]. PMID- 20290200 TI - [Not Available]. PMID- 20290201 TI - [Not Available]. PMID- 20290202 TI - [Not Available]. PMID- 20290203 TI - [Not Available]. PMID- 20290204 TI - [Not Available]. PMID- 20290205 TI - [Not Available]. PMID- 20290206 TI - Teething; a natural process. PMID- 20290207 TI - Tuberculous epiphysitis. PMID- 20290208 TI - Nursing problems of morphia addicts. PMID- 20290209 TI - Breech presentations. PMID- 20290210 TI - Treatment of compound fractured femur, as carried out at R.A.F. base hospital. PMID- 20290211 TI - Transverse lie and twins. PMID- 20290212 TI - Acidosis and cyclical vomiting. PMID- 20290213 TI - Acute inversion of the uterus; surgical treatment by fluid pressure. PMID- 20290214 TI - Moulds, fungi, and medicine. PMID- 20290215 TI - Hernia, types and their treatment. PMID- 20290216 TI - Amputation of leg of elderly woman under refrigeration anaesthesia. PMID- 20290217 TI - What to teach in home-making training. PMID- 20290219 TI - Standardisation of insulin by the use of rabbits. PMID- 20290218 TI - Sedatives, analgesics and stimulants used in labour. PMID- 20290220 TI - Sterility and subfertility. PMID- 20290221 TI - Hernia; its types and treatment. PMID- 20290222 TI - Mission hospital, an account of the work of an Indian missionary hospital. PMID- 20290223 TI - Asphyxia and birth injury. PMID- 20290224 TI - Hirschsprung's disease. PMID- 20290225 TI - Abdominal tuberculosis. PMID- 20290226 TI - Streptomycin; an assessment of its therapeutic value today. PMID- 20290227 TI - Abdominal tuberculosis. PMID- 20290229 TI - Artificial feeding and weaning. PMID- 20290228 TI - The risks to the child during labour; other contributing causes. PMID- 20290230 TI - Anxious parents and problem children. PMID- 20290231 TI - Transthoracic partial oesophago-gastrectomy; the pre-operative and post-operative treatment. PMID- 20290232 TI - Infant feeding; difficulties. PMID- 20290233 TI - Report on survey of optical aids for subnormal vision. PMID- 20290234 TI - Causes of early loss of light output of fluorescent lamps. PMID- 20290235 TI - Polanret microscopy. PMID- 20290236 TI - The hardening of ophthalmic lenses. PMID- 20290237 TI - The relation of the length of a border to its visibility. PMID- 20290238 TI - Size, shape, and contrast in the daytime detection of targets. PMID- 20290239 TI - A new galvanometer for radiometric measurements at low frequencies. PMID- 20290240 TI - Color adaptations to stimuli of different spectral composition but equal I. C. I. specification. PMID- 20290241 TI - Lens design and tolerance analysis methods and results. PMID- 20290242 TI - Use of incompletely consumed samples to illustrate effect of fractional distillation in carbon arc spectrochemical analyses. PMID- 20290243 TI - Visual thresholds of steady point sources of light in fields of brightness from dark to daylight. PMID- 20290244 TI - [Methods of tissue therapy; treatment with biogenous stimulators]. PMID- 20290246 TI - [Tissular treatment of traumatic iridocyclitis after Filatov's method]. PMID- 20290245 TI - [Treatment of pigmentary retinitis with autoclaved extract of aloes]. PMID- 20290247 TI - [Tissular therapy of traumatic changes of the vitreous in war medicine]. PMID- 20290248 TI - [Tissular therapy of atrophy of the optic nerve]. PMID- 20290249 TI - [Tissular therapy of contusional changes of the eye fundus with perforation defects of the macula lutea]. PMID- 20290250 TI - [Denig's operation and transplantation of conserved tissues after Filatov; method in treatment of pannus trachomatosus]. PMID- 20290251 TI - [Tissular therapy after the data of the Eye Clinic of the First Moscow Lenin's Order Medical Institute]. PMID- 20290252 TI - [Perspective of optical transplantation of the cornea]. PMID- 20290253 TI - [Preservation of the sensitivity of a wall-eye as a condition for the hyaline implantation in corneal plastic surgery]. PMID- 20290254 TI - [Transplantation of the cornea in wall-eyes in soldiers]. PMID- 20290255 TI - [Biological index to 124 operations of optical transplantation of the cornea]. PMID- 20290256 TI - [Preparation of cadres of physician-oculists]. PMID- 20290257 TI - [Tasks in the ophthalmological preparation of physicians in our universities]. PMID- 20290258 TI - [Penicillin therapy in ophthalmology]. PMID- 20290259 TI - [Use of penicillin in ophthalmology]. PMID- 20290260 TI - [Treatment of blennogonorrhea in newborn]. PMID- 20290261 TI - [Treatment of corneal ulcers with sulfidine]. PMID- 20290262 TI - [Treatment of septic diseases of the eyes and of the cranium contents by infusions of sulfonamides through the cavernous bodies of the lower conchae nasales]. PMID- 20290263 TI - [Use of both sulfidine and sulfazol in ophthalmology]. PMID- 20290264 TI - [Experimental administration of vitamin K in intraocular hemorrhage]. PMID- 20290265 TI - [Synthetic arecoline of Russian origin]. PMID- 20290266 TI - [Bismuth-oil preparations in ophthalmology]. PMID- 20290267 TI - [Use of jebalite in ophthalmology]. PMID- 20290268 TI - [Use of ether in corneal ulcer]. PMID- 20290269 TI - Sluchai khondromy orbity. [Chondroma of the orbit; case]. PMID- 20290270 TI - [Hyperplasia of the iris; case]. PMID- 20290271 TI - Congenital cysts of the tongue, the floor of the mouth, the pharynx and the larynx. PMID- 20290272 TI - The junction of the nasal cavity and the pharyngeal tube in the rat. PMID- 20290273 TI - Streptomycin used in the treatment of supurative otitis media; a preliminary report. PMID- 20290274 TI - Measurement of the overflow capacity of the maxillary sinus and its significance. PMID- 20290275 TI - Role of columellar and septocolumellar sutures in rhinoplasty. PMID- 20290276 TI - Dental treatment of trismus, tinnitus, otalgia and obscure neuralgias. PMID- 20290277 TI - Correction of prominent ears. PMID- 20290278 TI - An acrylic obturator employed in the repair of an obstructed frontonasal duct. PMID- 20290279 TI - Otosclerosis; an index of the literature, with abstracts, for 1944-1945. PMID- 20290280 TI - Peroral endoscopy. PMID- 20290282 TI - The beginnings of a methodology for social control studies in public address. PMID- 20290281 TI - A century and a third of speech training at Hamilton College. PMID- 20290283 TI - Speech in a communication course. PMID- 20290284 TI - Oregon's speech improvement and rehabilitation program. PMID- 20290285 TI - The state of speech correction. PMID- 20290286 TI - The relation between training and teaching activities of college teachers of speech. PMID- 20290287 TI - Speech in an orientation course for the ninth grade. PMID- 20290288 TI - Some suggested units on voice and articulation for secondary schools. PMID- 20290289 TI - [Questions concerning the treatment of war disabled with sequels of ORL lesions and ORL contusions in Russian hospitals]. PMID- 20290290 TI - K organizacii oto-laringologicheskogo hospitalia Mosgorzdravotdela invalidov otechestsvennoi voiny. [Organization of the ORL hospital in Moscow]. PMID- 20290291 TI - [Statistics of ORL injuries in the war]. PMID- 20290292 TI - Sredinno e sechenie miagkogo neba pri operaciiakh v nosoglotke. [Median section of the soft palate in operations on the nasopharynx]. PMID- 20290293 TI - [Radical ear operations]. PMID- 20290294 TI - [Conservative radical operation of the ear after Voyachek and postoperative treatment by insufflation with white streptocide]. PMID- 20290295 TI - [Petrositis of gunshot origin]. PMID- 20290296 TI - [Histopathological deformations in internal ear of animals in chronic purulent inflammation of cavum tympani]. PMID- 20290297 TI - [Experimental endonasal blood transfusion]. PMID- 20290298 TI - [Tumor-like form of scleroma with malignant course]. PMID- 20290299 TI - [Metastasis of a hypernephroid cancer into antrum]. PMID- 20290300 TI - [Kharkhov ORL schools]. PMID- 20290301 TI - The influence of chemical constitution on toxicity; a general survey of the acridine series. PMID- 20290302 TI - The precision of plasma volume determinations by the Evans blue method. PMID- 20290303 TI - Anticollagenase in immunity to Cl. welchii type A infection. PMID- 20290304 TI - An antibiotic from Penicillium tardum. PMID- 20290305 TI - Antibiotics from Stereum hirsutum. PMID- 20290306 TI - Studies on experimental goitre; thyroid tumours in rats treated with thiourea. PMID- 20290307 TI - Investigation into the production of bacteriostatic substances by fungi; preliminary examination of the sixth 100 species, more basidiomycetes of the wood destroying type. PMID- 20290308 TI - The role of coagulase in staphylococcal infections. PMID- 20290309 TI - Pathogenesis of passive Rh isosensitization in the newborn (erythroblastosis fetalis). PMID- 20290310 TI - Pathogenesis of mongolism. PMID- 20290311 TI - Blood pressure of normal girls from three to sixteen years of age. PMID- 20290312 TI - Alexander's rabbit serum in the treatment of influenzal meningitis; an evaluation of its use in conjunction with sulfonamide compounds. PMID- 20290313 TI - Xanthoma tuberosum, aortic stenosis, coronary sclerosis and angina pectoris; report of a case in a boy 13 years of age. PMID- 20290314 TI - Pyloric stenosis in twins; review of the literature and report of a case. PMID- 20290315 TI - Absence of bowel movements from birth [intestine, atresia]. PMID- 20290316 TI - Pains in the joints, stomach-ache [hyperparathyroidism]. PMID- 20290317 TI - [Not Available]. PMID- 20290318 TI - [Not Available]. PMID- 20290320 TI - [Not Available]. PMID- 20290319 TI - [Not Available]. PMID- 20290321 TI - [Not Available]. PMID- 20290322 TI - [Not Available]. PMID- 20290323 TI - [Not Available]. PMID- 20290324 TI - [Not Available]. PMID- 20290325 TI - [Not Available]. PMID- 20290326 TI - [Not Available]. PMID- 20290327 TI - [Not Available]. PMID- 20290328 TI - [Not Available]. PMID- 20290329 TI - [Not Available]. PMID- 20290330 TI - [Not Available]. PMID- 20290331 TI - [Not Available]. PMID- 20290332 TI - [Not Available]. PMID- 20290333 TI - [Not Available]. PMID- 20290334 TI - [Not Available]. PMID- 20290335 TI - [Not Available]. PMID- 20290337 TI - [Not Available]. PMID- 20290336 TI - [Not Available]. PMID- 20290338 TI - [Not Available]. PMID- 20290340 TI - [Not Available]. PMID- 20290339 TI - [Not Available]. PMID- 20290341 TI - [Not Available]. PMID- 20290342 TI - [Not Available]. PMID- 20290343 TI - [Not Available]. PMID- 20290344 TI - [Not Available]. PMID- 20290345 TI - [Not Available]. PMID- 20290346 TI - Effects of maternal under nutrition upon the newborn infant in Holland (1944 1945). PMID- 20290347 TI - Infantile mortality in Budapest in the year 1945; as reflected by the material of the children's clinic of the university. PMID- 20290348 TI - Children born during the siege of Leningrad in 1942. PMID- 20290349 TI - Airblock in the newborn infant. PMID- 20290350 TI - Sulfadiazine prophylaxis in children and adolescents with inactive rheumatic fever. PMID- 20290351 TI - The cardiopathy of sickle cell anemia and its differentiation from rheumatic carditis. PMID- 20290352 TI - Factors in the etiology of congenital heart anomalies. PMID- 20290353 TI - Dacryostenosis. PMID- 20290354 TI - Intestinal obstruction of the newborn; a report of five patients successfully relieved by surgery. PMID- 20290355 TI - General anesthesia in the difficult pedodontic patient. PMID- 20290356 TI - Reaction in tibia following intramedullary administration of fluids. PMID- 20290357 TI - Meningitis complicating cephalhematoma. PMID- 20290358 TI - Some aspects of the medical profession in Sweden. PMID- 20290359 TI - Thiouracil in childhood hyperthyroidism. PMID- 20290360 TI - Infectious hepatitis in childhood; a report of two institutional outbreaks and a comparison of the disease in adults and children. PMID- 20290361 TI - Hypercalcemia and idiopathic hyperplasia of the parathyroid glands in an infant. PMID- 20290362 TI - Bone marrow infusion in childhood; experiences from a thousand infusions. PMID- 20290363 TI - The estimation of extracellular and total body water in the newborn human infant with radioactive sodium and deuterium oxide. PMID- 20290364 TI - Renal glycosuria associated with pentosuria. PMID- 20290365 TI - Poisoning due to ingestion of wax crayons; report of a case. PMID- 20290366 TI - Double aortic arch. PMID- 20290367 TI - Acute meningococcemia. PMID- 20290368 TI - The comparative effect of parenteral administration of single massive doses of vitamin D in an oil-ether vehicle. PMID- 20290369 TI - Capillary fragility and menses in rheumatic girls. PMID- 20290370 TI - Meningitis due to Salmonelia manhattan. PMID- 20290371 TI - Hypertrophic pulmonary osteoarthropathy. PMID- 20290372 TI - Fatal sickle cell anemia in a one-month old infant. PMID- 20290373 TI - Encephalitis associated with herpes zoster. PMID- 20290374 TI - Compulsory prepaid medical care. PMID- 20290375 TI - [Our tasks in the five-year plan 1946-1950]. PMID- 20290376 TI - [Kidneys and urinary tract in pyuria in children]. PMID- 20290377 TI - [Contribution to formation and destruction of erythrocytes in children's dystrophia]. PMID- 20290378 TI - [Determination of vitamine C activity in human milk]. PMID- 20290379 TI - [Alimentary-toxic aleukia (septic angina) in children]. PMID- 20290380 TI - [Exposure of the nerve centers for the treatment of pathological conditions in children]. PMID- 20290381 TI - [Treatment of diphtheria with peracetine]. PMID- 20290382 TI - [Physical development and state of children's health during the years of the war]. PMID- 20290383 TI - [Etiology and dietetics of nephritis in children]. PMID- 20290384 TI - [Tasks next in turn in child health]. PMID- 20290385 TI - [Outline of treatment in children's sanatoriums in Eupatoria seaside resort]. PMID- 20290386 TI - [Experimental work of a tuberculosis unit in a kindergarten in wartime]. PMID- 20290387 TI - [Use of disulfane in bacillary dysentery in children]. PMID- 20290388 TI - [Perforation of the intestine in newborns and its pathogenesis]. PMID- 20290389 TI - A study of child health services. PMID- 20290390 TI - [Parenteral infusion of proteinogenic substances which stimulate activity]. PMID- 20290391 TI - [Role of the sympathetic nervous system in the changes of subordinational conditions in the central nervous system under the action of morphine]. PMID- 20290393 TI - [Pharmacology of sulfanylcyanamide]. PMID- 20290392 TI - [Pharmacology of sulfadiazine]. PMID- 20290394 TI - [Relation of chemical structure to pharmacological action in derivatives of pyrimidazole]. PMID- 20290395 TI - [Toxicity of sovcaine and its diminution under preliminary administration of glucose]. PMID- 20290396 TI - [Action of folinerine on diuresis]. PMID- 20290397 TI - [Detection of sulfurated hydrogen in the blood of poisoned animals]. PMID- 20290398 TI - [Adsorption of sulfurous gas in respiratory tract]. PMID- 20290400 TI - [Further development of medical industry]. PMID- 20290399 TI - [Mixed and combined effects of certain barbiturates (medinal and hexenal), with chloroform, ether, and alcohol on the isolated heart of the frog]. PMID- 20290401 TI - [Pharmacy in the first postwar five-year plan]. PMID- 20290402 TI - [Organization of drug supply to rural and regional dispensaries]. PMID- 20290403 TI - [Drug supply to Leningrad during the war]. PMID- 20290404 TI - [Methylcaffeine]. PMID- 20290405 TI - [Obtaining medicinal preparations from the fruits of Carum ajovan]. PMID- 20290406 TI - [Obtaining both Glauber's and Epsom salts from astrakhanite]. PMID- 20290407 TI - [Aminometric titrating of alkaloids]. PMID- 20290408 TI - [Alkalimetric method of determination of sulfidine]. PMID- 20290409 TI - [Season for gathering spring Adonis]. PMID- 20290410 TI - [Galenicals in the new editions of Pharmacopeia XII and National Formulary VII of USA]. PMID- 20290411 TI - [Let us secure uninterrupted drug supply to the population]. PMID- 20290412 TI - [Pharmacy and drug industry for the 25 years of Soviet Government in Azerbaijan]. PMID- 20290413 TI - [Qualitative semi-microchemical analysis]. PMID- 20290414 TI - [Vacuum method of dispersion and its practical applications]. PMID- 20290415 TI - [Filtration and percolation of solution of potassium hypermanganicum and silver nitrate]. PMID- 20290416 TI - [Quantitative determination of sulfidine as silver salt]. PMID- 20290417 TI - [Dry aqueous extraction of medicinal plants]. PMID- 20290418 TI - [New hemostatic agent from male flowers of maize and mechanism of its effect]. PMID- 20290419 TI - [Strepturin]. PMID- 20290420 TI - [Substitution of mint tincture in stomachic drops with tincture of Coriandrum]. PMID- 20290421 TI - [Nomenclature of drugs]. PMID- 20290422 TI - The toxicity and analgetic potency of salicylamide and certain of its derivatives as compared with established analgetic-antipyretic drugs. PMID- 20290423 TI - Glucuronic acid excretion after diethylene glycol monoethyl ether (carbitol) and some other glycols. PMID- 20290424 TI - A comparison of the bronchodilator activity of benadryl with some of its derivatives and certain other substances. PMID- 20290425 TI - Anesthesia; the effect of cholesterol on pentothal and ether anesthesia. PMID- 20290426 TI - A toxicologic study of two histamine antagonists of the benzhydryl alkamine ether group. PMID- 20290427 TI - Comparative activity of various antihistaminic substances towards the vasodepressor response to histamine. PMID- 20290429 TI - Circulatory properties of iso-thioureas, guanidines, iso-ureas and amidines. PMID- 20290428 TI - Pharmacological properties of antihistamine drugs, benadryl, pyribenzamine and neoantergan. PMID- 20290430 TI - The pharmacology of benzyl-imidazoline (Priscol). PMID- 20290431 TI - Factors influencing the toxicity of sympathomimetic amines to solitary mice. PMID- 20290432 TI - [Career of Aleksandr Vasil'evich Leontovich]. PMID- 20290433 TI - [Experimental neurosis due to emotional shock]. PMID- 20290434 TI - [Effect of low air pressures on visual after images]. PMID- 20290435 TI - [Duplex nature of motor excitations in the central nervous system]. PMID- 20290436 TI - [Problem of irradiation of excitations from the respiratory center over the central nervous system; respiratory contractions of the extremity muscles]. PMID- 20290437 TI - [Effect produced on the permeability of the uveal tract vessels by stimulation of the cerebellum]. PMID- 20290438 TI - [Current problems of neurophysiology]. PMID- 20290439 TI - [Changes in motor chronaxia in infants during sleep; at age of 2 weeks to 2 months]. PMID- 20290441 TI - [Possibility of inducing a single tetanized contraction of a neuromuscular preparation under normal physiological conditions]. PMID- 20290440 TI - [Changes in motor chronaxia in infants during sleep; at age of one to ten days]. PMID- 20290442 TI - [Biological activity of the thyroid gland and of the anterior lobe of the hypophysis]. PMID- 20290443 TI - [Specific dynamic action of proteins at high altitudes]. PMID- 20290444 TI - [Experimental food regimen for high altitude climate]. PMID- 20290445 TI - [History of ideas concerning function of the pituitary]. PMID- 20290446 TI - Symposium on personality; reply to criticisms and conclusion. PMID- 20290447 TI - Student selection by means of psychological tests; a critical survey. PMID- 20290448 TI - The factorial analysis of human ability [Bk Rev.]. PMID- 20290449 TI - The nature and cause of maladjustments in boys of normal and supernormal intelligence referred for clinical treatment. PMID- 20290450 TI - Truancy; a study of mental, scholastic, and social conditions in the problem of non-attendance at school. PMID- 20290451 TI - Attitudes of an age group to poetry. PMID- 20290452 TI - An attempt to condition the chronic spinal dog. PMID- 20290453 TI - Reactively heterogeneous compound trial-and-error learning with distributed trials and terminal reinforcement. PMID- 20290454 TI - Reaction time as a measure of retroactive inhibition. PMID- 20290456 TI - Reminiscence following experimentally induced failure. PMID- 20290455 TI - A study of muscle action potentials during the attempted solution by children of problems of increasing difficulty. PMID- 20290458 TI - The relationship of exposure time and accuracy in a perceptual task. PMID- 20290459 TI - Development of speech during infancy; curve of phonemic frequencies. PMID- 20290457 TI - The illusory perception of movement caused by angular acceleration and by centrifugal force during flight; methodology and preliminary results. PMID- 20290460 TI - The meaning of Koch and Daniel's results for Hull's theory. PMID- 20290462 TI - Help-hinder comparison in PK tests. PMID- 20290461 TI - PARAPSYCHOLOGY and ethics. PMID- 20290463 TI - A second classroom ESP experiment with the response method. PMID- 20290464 TI - Target preference in PK tests with dice. PMID- 20290465 TI - A PK experiment under light and dark conditions. PMID- 20290466 TI - Dice bias and manner of throwing. PMID- 20290467 TI - The physical significance of I'SI experiments. PMID- 20290468 TI - [Plan of state sanitary inspection in the postwar period]. PMID- 20290469 TI - [Tasks next in turn in study of physical development of children and young]. PMID- 20290470 TI - [Photoelectric devices; objective luxometer]. PMID- 20290471 TI - [Problems of sanitation in use of halowax]. PMID- 20290472 TI - [Sources of hydrogen sulfide leak at excavation work in Krasnovodsk harbor and preventive measures]. PMID- 20290473 TI - [Nutrition in postwar period]. PMID- 20290474 TI - [Nicotinic acid in rye bread baked with potatoes]. PMID- 20290475 TI - [Milk coagulation test for coli and the sphere of its employment]. PMID- 20290476 TI - [Methods of isolation of pathogenic microbes of the intestinal-typhoid group from contaminated waters]. PMID- 20290477 TI - [Self-disinfecting bacteria-fast cloths and their uses]. PMID- 20290478 TI - [Survey of papers by M. G. Kichenko on sanitary bacteriology]. PMID- 20290479 TI - [Effect of cold on bacteria]. PMID- 20290480 TI - [Regeneration of used and intergrown agar]. PMID- 20290481 TI - [Identification of intestinal typhoid bacteria]. PMID- 20290482 TI - [Elective toxic action of krysid, alpha-naphthyl-urea, for certain animals]. PMID- 20290483 TI - [Work of Baku house in sanitary education in prevention of industrial accidents]. PMID- 20290484 TI - [Self-acting disinfector for toilets provided with sewer connection]. PMID- 20290485 TI - [Plan of state sanitary inspection in the postwar period]. PMID- 20290486 TI - [Questions next in turn of verdification of towns]. PMID- 20290488 TI - [Ply antiseptic-tank covers]. PMID- 20290487 TI - [Removal of residual matter from mixerless sand filters and prevention of growths]. PMID- 20290489 TI - [Improvement of well-water supply]. PMID- 20290490 TI - [Corrugated glass in shops]. PMID- 20290491 TI - [Influence of some chemical intoxications on so-called common (not industrial) morbidity]. PMID- 20290492 TI - [Protection from mice]. PMID- 20290493 TI - [Rural morbidity]. PMID- 20290494 TI - [Experimental propagation of vitamins]. PMID- 20290495 TI - [Changes in the composition of underground water used for water supply]. PMID- 20290496 TI - [Nature of a bactericidal factor contained in water]. PMID- 20290497 TI - [Metal clothing for some workers employed in hot workshops]. PMID- 20290498 TI - [Vitamin B-1 and PP content in raw and cooked mushrooms]. PMID- 20290499 TI - [Length of storage of bread]. PMID- 20290500 TI - [New method for determining the caloric value of food]. PMID- 20290501 TI - [Sanitary characteristics of the microflora in well and spring waters and in waters from artificial reservoirs in Samarkand]. PMID- 20290502 TI - [Training of sanitary medical officers]. PMID- 20290503 TI - [Systematic aid for leading personnel in public health]. PMID- 20290504 TI - [Bathhouse service for the population of Kasakhstan during the war]. PMID- 20290505 TI - [Four years experience in the work of sanitary epidemiology in the army]. PMID- 20290506 TI - [Conference of institutes and chairs of hygiene in the USSR]. PMID- 20290507 TI - [Conference on programs of institutes of hygiene of the RSFSR]. PMID- 20290508 TI - [Conference of institutes of industrial hygiene and occupational diseases]. PMID- 20290509 TI - [ACTIVITIES of the All Union Society of Hygiene]. PMID- 20290510 TI - [Hygienic basis for the selection of sources for centralized water supply and their sanitary evaluation]. PMID- 20290511 TI - [Ozonization of water]. PMID- 20290512 TI - [Condition of central water supply in the cities of White Russian SSR and sanitary measures of postwar reconstruction]. PMID- 20290513 TI - [Water-supply in the Ust-Ordin district of the Irkutsk region and means of its reconstruction]. PMID- 20290515 TI - [Purification of compressed air for caissons]. PMID- 20290514 TI - [Prevention of mercury poisoning in workers]. PMID- 20290517 TI - [Review of articles on industrial hygiene problems received by the editorial board]. PMID- 20290516 TI - [Colorimetric detection of copper by means of sodium diethyldithiocarbamate]. PMID- 20290518 TI - [A new colorimetric method for determination of protein in food]. PMID- 20290519 TI - [Vitamin C in con fresh' sauerkraut]. PMID- 20290520 TI - [Data on the biology of flies in connection with the elaboration of a method for fly control]. PMID- 20290521 TI - [Soviet laws concerning living conditions of sanitary medical officers]. PMID- 20290522 TI - [Rapid methods for the detection of harmful impurities in sodium chloride used for food]. PMID- 20290523 TI - [Diacid methods for detection of fats in milk and milk products]. PMID- 20290524 TI - [Examination of cloakroom tags in Leningrad Maritime district]. PMID- 20290525 TI - Army water supply in World War II. PMID- 20290526 TI - Enemy water supply equipment. PMID- 20290527 TI - Co-operative sanitation in the Americas. PMID- 20290528 TI - Bacterial oxidation of ammonia in circulating water. PMID- 20290529 TI - A photometric method for the comparative evaluation of disinfectants. PMID- 20290530 TI - A standardized method of disinfecting infected blood-clots. PMID- 20290531 TI - The growth of bacterial colonies and their viable population. PMID- 20290532 TI - Mode of origin of sulphonamide-resistant strains in B. dysenteriae Flexner. PMID- 20290533 TI - The bacteriology of dehydrated vegetables. PMID- 20290534 TI - A comparative study of phenolized and alcoholized T. A. B. vaccines. PMID- 20290535 TI - Agglutination and complement fixation in human and rabbit typhoid and dysentery sera and the specificity of complement. PMID- 20290536 TI - Efficacy of protein hydrolysate in the restoration of serum protein in hyperimmunized horses after blood depletion. PMID- 20290537 TI - The digestibility of English and Canadian wheats with special reference to the digestibility of wheat protein by man. PMID- 20290538 TI - Clinical nutritional surveys; relationship between observed signs. PMID- 20290539 TI - Feeding and breeding of laboratory animals; observations on the feeding of guinea pigs. PMID- 20290540 TI - The vitamin A reserve of the population in Denmark and Norway during the war. PMID- 20290541 TI - Some skin manifestations in hypoparathyroidism. PMID- 20290542 TI - Nutritional deficiency and resistance to infection; the effect of caloric and protein deficiency on the susceptibility of rats and mice to infection with Salmonella typhi murium. PMID- 20290543 TI - The popular history of anaesthesia. PMID- 20290544 TI - The future control of abattoirs and knackeryards. PMID- 20290545 TI - The welfare of old people. PMID- 20290546 TI - The mental health of the elderly. PMID- 20290547 TI - Health centres. PMID- 20290548 TI - Height, weight and age charts for children of school age; a simplified method of computation. PMID- 20290549 TI - Housing in relation to health. PMID- 20290550 TI - [Lymph circulation in traumatic lesions of the extremities in dogs]. PMID- 20290551 TI - [Angiography in diseases of the peripheral vascular system]. PMID- 20290552 TI - [Intravenous urography in closed lesions of the kidneys; experimental]. PMID- 20290553 TI - [Cerebral pneumography in epilepsy and hydrocephalus]. PMID- 20290554 TI - [On the problem of peptic ulcer of the esophagus]. PMID- 20290555 TI - [Two cases of heart wounds inflicted with a needle]. PMID- 20290556 TI - [Metro salpingography in female sterility]. PMID- 20290557 TI - [Problem of cysticercosis]. PMID- 20290558 TI - [Roentgenography of muscular cysticercosis]. PMID- 20290559 TI - [Etiological role of blastomogenic substances]. PMID- 20290560 TI - [Analysis of the convulsion process caused by the effect of radium rays on the central nervous system of the frog]. PMID- 20290561 TI - [Constitutional subordination chronaxia of the peripheral nerves caused by the effect of radium rays on the central nervous system of the frog]. PMID- 20290562 TI - [Effect of radium emanation on the course run by conditioned reflexes in the dog]. PMID- 20290563 TI - [Roentgenotherapy of essential dysmenorrhea]. PMID- 20290565 TI - [Not Available]. PMID- 20290564 TI - [Lesions of the skeleton in leukemia]. PMID- 20290566 TI - [Not Available]. PMID- 20290567 TI - [Not Available]. PMID- 20290568 TI - [Not Available]. PMID- 20290569 TI - [Not Available]. PMID- 20290570 TI - [Not Available]. PMID- 20290571 TI - [Not Available]. PMID- 20290572 TI - [Not Available]. PMID- 20290573 TI - [Not Available]. PMID- 20290574 TI - [Not Available]. PMID- 20290575 TI - [Not Available]. PMID- 20290576 TI - [Not Available]. PMID- 20290577 TI - [Not Available]. PMID- 20290578 TI - [Not Available]. PMID- 20290579 TI - Management of extensive complete defects in long bones. PMID- 20290580 TI - Use and abuse of intestinal decompression tube; a study based upon 200 cases. PMID- 20290581 TI - Wounds of the colon and rectum. PMID- 20290582 TI - Meckel's diverticulum; review of literature and analytical study of 23 cases with particular emphasis on bowel obstruction. PMID- 20290583 TI - Ultraviolet blood irradiation therapy; further studies in acute infections. PMID- 20290584 TI - Myophagism congenita. PMID- 20290585 TI - Use of tantalum for facial and cranial defects. PMID- 20290586 TI - Strictures following transurethral resection; comments on the indication for the operation. PMID- 20290587 TI - Solitary pyogenic abscess of the liver. PMID- 20290588 TI - Carcinoma of the breast following burn. PMID- 20290589 TI - Tuberculous salpingitis. PMID- 20290590 TI - Box operating table; a simple device for infants. PMID- 20290591 TI - [Not Available]. PMID- 20290592 TI - [Not Available]. PMID- 20290593 TI - [Not Available]. PMID- 20290594 TI - [Not Available]. PMID- 20290595 TI - [Not Available]. PMID- 20290596 TI - [Not Available]. PMID- 20290598 TI - [Not Available]. PMID- 20290597 TI - [Not Available]. PMID- 20290599 TI - [Not Available]. PMID- 20290600 TI - [Not Available]. PMID- 20290602 TI - [Not Available]. PMID- 20290601 TI - [Not Available]. PMID- 20290603 TI - [Not Available]. PMID- 20290604 TI - [Not Available]. PMID- 20290605 TI - [Not Available]. PMID- 20290606 TI - [Not Available]. PMID- 20290607 TI - The pathology of chronic traumatic hemothorax. PMID- 20290608 TI - The treatment of organizing hemothorax by pulmonary decortication. PMID- 20290609 TI - Total pulmonary decortication; its evolution and present concepts of indications and operative technique. PMID- 20290610 TI - Hemothorax and empyema in a thoracic center. PMID- 20290611 TI - Pulmonary cysts. PMID- 20290612 TI - Transthoracic repair of large diaphragmatic hernias; an experimental study. PMID- 20290613 TI - Sympathectomy for peripheral vascular disease. PMID- 20290614 TI - Primary anastomosis in the treatment of carcinoma of the colon. PMID- 20290615 TI - The treatment of acute appendicitis in a closed city. PMID- 20290616 TI - Incomplete removal of the cystic duct as a factor in producing postcholecystectomy complications. PMID- 20290617 TI - Causalgia; a review of its characteristics, diagnosis, and treatment. PMID- 20290618 TI - Benign cavernous hemangioma of the spleen; literature review and case report. PMID- 20290619 TI - Cystadenoma of the pancreas; with presentation of one case and review of twenty eight cases collected from the medical literature. PMID- 20290620 TI - Aneurysm of renal artery; report of additional case. PMID- 20290621 TI - Clostridial wound infections and gas gangrene; arterial damage as a modifying factor. PMID- 20290622 TI - Penicillin in treatment of craniocerebral injuries of war; with particular reference to its intraventricular use. PMID- 20290623 TI - War wounds of the chest. PMID- 20290624 TI - Ceepryn as an antiseptic for the preoperative preparation of the skin. PMID- 20290625 TI - Hyperparathyroidism; a review of historical developments and the present state of knowledge on the subject. PMID- 20290626 TI - The surgical treatment of aneurysms of the abdominal aorta. PMID- 20290627 TI - Resection of primary liver tumors. PMID- 20290628 TI - A one-stage pharyngoesophageal diverticulectomy. PMID- 20290629 TI - Surgical management of carcinoma of the right portion of the colon with secondary involvement of the duodenum, including duodenocolic fistula; data on eight cases. PMID- 20290630 TI - The McArthur operation for inguinal hernia. PMID- 20290631 TI - Incisional hernia, operative technique. PMID- 20290632 TI - Adenomatous goiter without hyperthyroidism; surgical versus conservative treatment in over 200 patients. PMID- 20290633 TI - Gastric resection for peptic ulcer; a study of 221 consecutive cases. PMID- 20290634 TI - Congenital hypertrophic pyloric stenosis. PMID- 20290635 TI - Lesions of the ampulla of Vater. PMID- 20290636 TI - Enterogenous cysts of the duodenum; case report and review of literature. PMID- 20290637 TI - Intraperitoneal hemorrhage complicating simple large bowel obstruction. PMID- 20290638 TI - Tantalum cranioplasty, a method for one-piece fixation. PMID- 20290639 TI - The late definitive treatment of gunshot wounds of the head. PMID- 20290640 TI - Afferent conduction via the sympathetic ganglia innervating the extremities. PMID- 20290641 TI - Surgical management of vascular leg ulcers. PMID- 20290642 TI - A simple device to test and to improve the circulation in a pedicle flap. PMID- 20290644 TI - Effects of protein and methionine on nitrogen balance of burned rats. PMID- 20290643 TI - The treatment of superficial pyogenic infections by the direct injection of penicillin. PMID- 20290645 TI - Penetrating heart wound; the report of an interesting case. PMID- 20290646 TI - Subtertian malaria in white troops in West Africa; a review of 300 cases. PMID- 20290647 TI - Maintenance of Anopheles quadrimaculatus (in the laboratory). PMID- 20290648 TI - Adaptations of insects to changes of temperature. PMID- 20290649 TI - Sarcoptic mange in the alpaca, Lama huanaco var. paca. PMID- 20290650 TI - Illustrations of scrub typhus in Burma and Assam. PMID- 20290651 TI - Chromosomes of mosquitoes. PMID- 20290652 TI - The control of re-radiated solar heat by whitewash. PMID- 20290653 TI - A unique form of Histoplasma. PMID- 20290654 TI - Malaria control measures in the vicinity of the town and port of Lagos. PMID- 20290655 TI - Distribution of paludrine in whole blood and plasma. PMID- 20290656 TI - The mechanism of renal anoxia; evidence of a renal vascular reflex and the establishment of collateral renal circulation in the rabbit. PMID- 20290657 TI - Smears and sections showing the primary phase of P. gallinaceum at the site of inoculation with sporozoites. PMID- 20290658 TI - Methods employed in investigations on the transmission of Litomosoides carinii by Liponyssus bacoti. PMID- 20290659 TI - Tropical phlebitis in Northern Rhodesia; sections of biopsy material. PMID- 20290660 TI - A case of quartan malaria (P. malariae) brought about as the result of whole blood transfusion. PMID- 20290661 TI - A means of identifying the varieties of A. maculipennis adults by the shape and size of the scales of the wings. PMID- 20290662 TI - Apparatus for feeding blood-sucking insects in the laboratory. PMID- 20290663 TI - The diagnosis of threadworms. PMID- 20290664 TI - A new type of research microscope. PMID- 20290665 TI - Colonial nutrition and its problems. PMID- 20290666 TI - An epidemic of riboflavin deficiency in Indian troops. PMID- 20290667 TI - Ocular symptoms in prisoners of war in Sumatra. PMID- 20290668 TI - The complement fixation reaction in Asiatic schistosomiasis employing cercarial antigen (Schistosoma spindale). PMID- 20290669 TI - Sickle-cell anaemia in West Africa. PMID- 20290670 TI - The value of plasmoquine as a gametocide in sub-tertian malaria. PMID- 20290671 TI - The laboratory diagnosis of leprosy. PMID- 20290672 TI - The metabolism of rat lepromas and of rat leprosy bacilli. PMID- 20290673 TI - Studies in leishmaniasis in the Anglo-Egyptian Sudan; some observations on the chemotherapy of kala-azar. PMID- 20290674 TI - Bilharziasis in the Gezira irrigated area of the Sudan. PMID- 20290675 TI - Observations on Leptomonas etenocephali (Fantham, 1912). PMID- 20290676 TI - A new method of demonstrating malarial parasites in the peripheral blood. PMID- 20290677 TI - Case of severe reaction to antrypol. PMID- 20290678 TI - Porocephalosis. PMID- 20290679 TI - Cerebral lesions in dogs following injections of 4:4'diamidino-stilbene. PMID- 20290680 TI - The dispersal of respiratory pathogens in relation to the occurrence and control of air-borne infections. PMID- 20290681 TI - Experimental air-borne tuberculosis and its control. PMID- 20290682 TI - Discrepancies between clinical-radiological and bronchospirometric findings. PMID- 20290683 TI - Promizole treatment of miliary tuberculosis; toxic effects on thyroid gland and maturation. PMID- 20290684 TI - Pulmonary tuberculosis and season of birth. PMID- 20290685 TI - Carcinoma simulating pulmonary tuberculosis; differential diagnosis in the presymptomatic stage in two cases. PMID- 20290686 TI - Tuberculin testing in student nurses. PMID- 20290687 TI - A method of X-ray reproduction of the negative X-ray film. PMID- 20290688 TI - [Early forms of primary tuberculosis in adults]. PMID- 20290689 TI - [Ring-shaped tuberculous focus]. PMID- 20290690 TI - [Bacilli-status of tuberculosis in very young children]. PMID- 20290691 TI - [Efficiency of BCG immunization in the newborn]. PMID- 20290692 TI - [Isolated tuberculous osseous nidi during the period of primary complex of the lungs]. PMID- 20290693 TI - [Pathogenesis and clinics of polyserositis in the adult]. PMID- 20290694 TI - [Remote results of efficiency of artificial pneumothorax in tuberculosis of both lungs and larynx]. PMID- 20290695 TI - [Methods for sharpening hollow needles used in artificial pneumothorax]. PMID- 20290696 TI - [Agranulocytic syndrome in a tuberculous patient under treatment with chrysethane, a gold preparation]. PMID- 20290697 TI - [Rare case of tuberculous spondylitis in a patient with acute poliomyelitis]. PMID- 20290698 TI - Studies in streptomycin in tuberculosis; the action of streptomycin in experimental tuberculosis. PMID- 20290699 TI - Streptomycin in clinical tuberculosis. PMID- 20290700 TI - What's new and news in adult health education. PMID- 20290701 TI - What's new and news in school health education. PMID- 20290702 TI - What's new and news in group chest X-raying. PMID- 20290703 TI - What's new and news in public health nursing. PMID- 20290704 TI - What's new and news in rehabilitation. PMID- 20290705 TI - What's new and news in social developments affecting tuberculous patients. PMID- 20290706 TI - What's new and news in research in the campaign against tuberculosis. PMID- 20290707 TI - Making the most of group chest X-ray services; review of relative values of tuberculosis case-finding procedures. PMID- 20290708 TI - Making the most of group chest X-ray services; group X-raying and follow-up and follow-through, in a State. PMID- 20290709 TI - Making the most of group chest X-ray services; group X-raying and follow-up and follow-through in a large city, Philadelphia. PMID- 20290710 TI - Making the most of group chest X-ray services; group X-raying and follow-up and follow-through in a Canadian Province, Ontario. PMID- 20290711 TI - Tuberculosis associations; today and tomorrow; panel discussion. PMID- 20290712 TI - The tuberculosis program of the Veterans Administration. PMID- 20290713 TI - The National Tuberculosis Association and its interest in the tuberculosis veteran. PMID- 20290714 TI - New developments in tuberculosis control. PMID- 20290715 TI - Tuberculosis as an international problem. PMID- 20290716 TI - A resume of the tuberculosis experience of the U.S. Army in World War II. PMID- 20290718 TI - The late results of partial nephrectomy for calyectasis with stone. PMID- 20290717 TI - Let's improve the care and education of the tuberculosis patient in the hospital. PMID- 20290719 TI - Conservative treatment of renal and ureteral colic. PMID- 20290720 TI - Chronic typhoid pyonephrosis; report of a case. PMID- 20290721 TI - The surgical approach to renal and other retroperitoneal tumors. PMID- 20290722 TI - Distant metastases of 58 renal neoplasms; a case report of secondary metastatic pulsations from a renal tumor. PMID- 20290723 TI - Kidney tumors; a clinical and pathological study, with special reference to the hypernephroid tumor. PMID- 20290724 TI - Transplantation of the ureters into the rectosigmoid for exstrophy of the bladder; review of 41 cases. PMID- 20290725 TI - New technique of uretero-intestinal anastomosis; further report. PMID- 20290726 TI - Total cystectomy for infiltrating carcinoma of the bladder. PMID- 20290727 TI - The utilization of heat in the treatment of tumors of the urinary bladder; a presentation of technique. PMID- 20290728 TI - Anterolateral chordotomy for refractory interstitial cystitis with intractable pain. PMID- 20290729 TI - True prostatic calculus. PMID- 20290730 TI - Histopathological study of prostatic tissue following endoscopic prostatic resection. PMID- 20290731 TI - Chemistry of carcinoma of the prostate. PMID- 20290732 TI - Transurethral resection to relieve urinary retention following operations on the rectum and sigmoid. PMID- 20290733 TI - Genital histoplasmosis. PMID- 20290734 TI - Treatment of urinary tract obstruction due to sulfonamide crystals with special reference to lumbar sympathetic block. PMID- 20290735 TI - Perineal phlegmons and fistulae. PMID- 20290736 TI - Vesical dysfunction following recto-sigmoid resection. PMID- 20290737 TI - Non-fused pelvic kidney; a study of nine cases. PMID- 20290739 TI - Female urological symptoms as related to gynecology. PMID- 20290738 TI - Sympathetic tumors arising from the suprarenal medulla; report of case. PMID- 20290740 TI - Urinary tuberculosis. PMID- 20290741 TI - So-called triple bladder; report of a case of congenital diverticula. PMID- 20290742 TI - Idiopathic priapism; case report. PMID- 20290743 TI - Retardation of the aging process. PMID- 20290744 TI - Vitamin E and oestrogens in experimental and human blood dyscrasias. PMID- 20290745 TI - The cystoscope as an aid in office urology. PMID- 20290746 TI - Diagnostic errors in urology of immediate interest to the general practitioner. PMID- 20290747 TI - Some principles to be observed in the operation of transurethral prostatic resection. PMID- 20290748 TI - Pancreatin and some of its newer uses. PMID- 20290749 TI - Preliminary report on the use of diramin in treating tropical disease during 1944 and 1945. PMID- 20290750 TI - Adenocarcinoma of the vault of the urinary bladder. PMID- 20290751 TI - Metastatic epididymitis; with report of occurrence in an infant during acute respiratory infection. PMID- 20290752 TI - Lymphosarcoma of the bladder; with brief review of the literature. PMID- 20290754 TI - The non-organic albuminurias. PMID- 20290753 TI - Unilateral kidney disease and hypertension; report of four cases. PMID- 20290755 TI - Infections of the urinary tract and the complications arising therefrom. PMID- 20290756 TI - The pathology of urethritis and allied conditions in the female. PMID- 20290757 TI - Morphology of kidney tumors from the standpoint of the transition forms. PMID- 20290758 TI - Hemangioendothelioma of uterus. PMID- 20290759 TI - Carcinoma of urinary bladder with unusual metastases in a young male; clinicopathologic case report. PMID- 20290760 TI - Endoscopic resection of papillary tumors of the bladder. PMID- 20290761 TI - Bilateral testicular seminoma. PMID- 20290762 TI - The mechanism of the cutaneous manifestations of acute leukemia. PMID- 20290763 TI - VESICAL neck fibrosis. PMID- 20290764 TI - Present status of penicillin therapy in early syphilis. PMID- 20290765 TI - Spastic ureter. PMID- 20290766 TI - An evaluation of certain factors pertinent to surgery of the anterior vaginal wall. PMID- 20290767 TI - Uretero vesicovaginal fistula of obstetric origin; case report. PMID- 20290768 TI - Urological gynecology. PMID- 20290769 TI - The value of the Foley catheter in post-partum care. PMID- 20290770 TI - Urology in gynecology. PMID- 20290771 TI - Pelvic abscess and its relation to urological conditions. PMID- 20290772 TI - Gynecological operations in the treatment of stress incontinence of urine. PMID- 20290773 TI - Massive intra-abdominal hemorrhage of renal origin, complicating pregnancy, with recovery. PMID- 20290774 TI - Clinical report of the frequent association of trigonitis with chronic cervicitis and vaginitis; diagnosis and treatment. PMID- 20290775 TI - Differential diagnosis between gynecological and urogenital diseases. PMID- 20290776 TI - Experiences with the Johnson stone basket. PMID- 20290777 TI - Sarcoma of the bladder; a report of four cases. PMID- 20290778 TI - Prostatic surgery at Saint Louis City Hospital; report of 100 cases for a period of 10 months. PMID- 20290779 TI - Balanitis xerotica obliterans; a report of two cases. PMID- 20290781 TI - Health of the Army. PMID- 20290780 TI - Prevention is the watch-word; some social implications of the venereal diseases and their control. PMID- 20290782 TI - Working together to stamp out VD. PMID- 20290783 TI - The moral equivalent for law enforcement. PMID- 20290784 TI - What do young people want in a marriage partner? results of a questionnaire study of 559 young men and women. PMID- 20290785 TI - Venereal disease interviewing. PMID- 20290786 TI - The rural public health nurse in venereal disease control. PMID- 20290787 TI - RAPID treatment centers and hospitals providing in-patient treatment for venereal diseases. PMID- 20290788 TI - [Venereal and cutaneous diseases in the USA and in Canada, after personal observations]. PMID- 20290789 TI - [Experimental data on filtration through argentophile membranes]. PMID- 20290790 TI - [Pathogenesis of leprous sarcoid]. PMID- 20290791 TI - [Skin deformations under alimentary dystrophy and vitamin deficiencies]. PMID- 20290792 TI - [Lipoid metabolism in psoriasis; protein content and its fractions in serum of psoriatics]. PMID- 20290793 TI - [On certain peculiarities of the cellular reaction of the organism in patients with paratraumatic eczema]. PMID- 20290794 TI - Roentgenotherapy of skin diseases and its perspectives]. PMID- 20290795 TI - [Efficiency of syphilis treatment with mapharsen]. PMID- 20290796 TI - [The influence of malaria on the strength of Wassermann positive in syphilis]. PMID- 20290797 TI - [Administration of penicillin]. PMID- 20290798 TI - [Treatment with hyposulfite of gonorrhea resistant to sulfanilamides]. PMID- 20290799 TI - [Preliminary vaccination in therapy with streptocide of acute gonorrheal urethritis]. PMID- 20290800 TI - [Singular case of pathomimia]. PMID- 20290801 TI - [Gonorrheal ulcers of the skin]. PMID- 20290802 TI - Second report on the treatment of clinical streptococcal and staphylococcal infections of the bovine udder with penicillin. PMID- 20290803 TI - A survey of Victorian canine and vulpine parasites; Platyhelminthes other than Taenia multiceps, Taenia ovis and Echinococcus graulossus. PMID- 20290805 TI - A review of the veterinary aspects of bacterial food poisoning in man. PMID- 20290804 TI - Endocrinology and animal production. PMID- 20290806 TI - Some nutritional observations on the drought feeding of sheep. PMID- 20290807 TI - A survey of Victorian canine and vulpine parasites; Arthropoda. PMID- 20290808 TI - A note on two blood parasites of cattle (Spirochaeta theileri and Bartonella bovis) recorded for the first time in Australia. PMID- 20290809 TI - Cerebellar hypoplasia and degeneration in the kitten. PMID- 20290810 TI - Some surgical conditions of the intestines of dairy cattle. PMID- 20290811 TI - Diseases of the respiratory tract in fowls. PMID- 20290812 TI - Salmonellosis in swine. PMID- 20290813 TI - Swine dysentery. PMID- 20290814 TI - Enzootic fatal syncope (toxic heart degeneration) in fowls. PMID- 20290815 TI - The toxic properties of the volatile oil of Myoporum acuminatum R. Br. PMID- 20290816 TI - Haemorrhage into the floating colon as cause of death in equine colic. PMID- 20290817 TI - Clinical bovine mastitis, its treatment and control. PMID- 20290818 TI - Clinical bovine mastitis and its treatment. PMID- 20290819 TI - Animal research in New Zealand. PMID- 20290820 TI - A further note on metaplasia in the sex organs of castrated male sheep on subterranean clover pastures. PMID- 20290821 TI - Third report on the treatment of infections of the bovine udder with penicillin; treatment of persistent subclinical and of quiescent chronic Str. agalactiae infections and of clinical staphylococcal infections. PMID- 20290822 TI - The correlation of field and laboratory work in routine diagnosis. PMID- 20290823 TI - Nutritional deficiencies of poultry in New South Wales. PMID- 20290824 TI - Preliminary observations on the use of the penicillin bougie in the bovine udder. PMID- 20290825 TI - Selection of suitable antigenic strains of S. pullorum by single colony isolation. PMID- 20290827 TI - The differential blood picture in chickens before and after administration of embryonated eggs of Heterakis gallinae with notes on pathogenicity. PMID- 20290828 TI - The correlation of field and laboratory work in routine diagnosis. PMID- 20290829 TI - Clinical manifestations and treatment of bovine ringworm. PMID- 20290830 TI - The occurrence of vibrionic abortion in an Illinois dairy herd. PMID- 20290831 TI - Clinical studies on early equine abortion. PMID- 20290832 TI - The agglutination test as a means of detecting fowl typhoid infection. PMID- 20290833 TI - A study of infectious bronchitis in chickens; further observations on the carrier status of chickens recovered from infectious bronchitis. PMID- 20290834 TI - The value of physical examination of dairy herds to milk control programs. PMID- 20290835 TI - Listeriosis in Connecticut with particular reference to a septicemic case in a wild raccoon. PMID- 20290836 TI - Valvular endocarditis in the fowl. PMID- 20290838 TI - Treatment of four cases of bovine pyelonephritis with penicillin. PMID- 20290837 TI - Brucellosis eradication and its effect of production in a large swine herd. PMID- 20290839 TI - A case of quadruple pregnancy in the bovine. PMID- 20290840 TI - Successful treatment with penicillin of tetanus in a heifer. PMID- 20290841 TI - Studies on surra; cattle surra and some problems connected with the disease. PMID- 20290842 TI - Acute bovine trypanosomiasis in Madras Presidency. PMID- 20290843 TI - A note on chronic infected wounds in animals. PMID- 20290844 TI - A clinical investigation on contagious gastro-enteritis in sheep at the Livestock Research Station, Hosur. PMID- 20290845 TI - Incidence of anthrax in sheep, goats and cattle in Baroda State. PMID- 20290846 TI - Skin disease (leucoderma?) in a buffalo-bull. PMID- 20290847 TI - Uro-lithiasis in a bullock. PMID- 20290848 TI - Fracture of radius and ulna in a Pomeranian dog. PMID- 20290849 TI - Penicillin dosage and blood levels for sheep and calves. PMID- 20290850 TI - Further trials with hexachloroethane as a treatment for liver fluke in Oregon cattle. PMID- 20290851 TI - Tyrothricin ointment in the treatment of udder and teat injuries. PMID- 20290852 TI - Posterior paralysis associated with intervertebral disc protrusion in the dog. PMID- 20290853 TI - LEUCOCYTOZOON infection in turkeys. PMID- 20290854 TI - What the U.S. Army did for the veterinary profession. PMID- 20290855 TI - Sulfaquinoxaline in the prevention of Eimeria tenella infections in chickens. PMID- 20290856 TI - Canine surgical problems. PMID- 20290857 TI - Dermoid cyst of the ovary. PMID- 20290858 TI - Fracture of the os penis. PMID- 20290859 TI - STREPTOMYCIN in the treatment of experimental relapsing fever and leptospirosis icterohaemorrhagica (Weil's disease). PMID- 20290860 TI - Semen as an index to the physiology and to the pathology of the male genital system. PMID- 20290861 TI - Urea poisoning in cattle. PMID- 20290862 TI - Black scours in cattle. PMID- 20290863 TI - Teniasis as a cause of running fits; a clinical report. PMID- 20290864 TI - A transplant method of repair of Achilles tendon. PMID- 20290865 TI - Dairy cattle practice. PMID- 20290866 TI - Leptospirosis. PMID- 20290867 TI - Some observations on the protein requirements of dogs. PMID- 20290868 TI - A hospital unit. PMID- 20290869 TI - Congenital defect of the skin. PMID- 20290870 TI - More about ovarian dysfunction. PMID- 20290871 TI - Sodium cacodylate and arsenic trioxide in anaplasmosis of cattle. PMID- 20290872 TI - Radiographs corroborate the diagnosis. PMID- 20290873 TI - Cages for hospitalized dogs. PMID- 20290874 TI - Leukemia in two dogs belonging to the same owner. PMID- 20290875 TI - [Not Available]. PMID- 20290876 TI - Over een nieuw type van het virus van Carre. PMID- 20290877 TI - [Not Available]. PMID- 20290878 TI - [Not Available]. PMID- 20290879 TI - [Not Available]. PMID- 20290880 TI - [Not Available]. PMID- 20290881 TI - [Not Available]. PMID- 20290882 TI - Heterose. PMID- 20290883 TI - [Not Available]. PMID- 20290885 TI - [Not Available]. PMID- 20290884 TI - [Not Available]. PMID- 20290886 TI - [Not Available]. PMID- 20290887 TI - [Not Available]. PMID- 20290888 TI - [Not Available]. PMID- 20290889 TI - [Not Available]. PMID- 20290891 TI - [Not Available]. PMID- 20290890 TI - [Not Available]. PMID- 20290892 TI - [Not Available]. PMID- 20290893 TI - [Not Available]. PMID- 20290894 TI - [Not Available]. PMID- 20290895 TI - [Not Available]. PMID- 20290896 TI - The effect of splenectomy and inanition on the bone marrow of plethodontid urodeles. PMID- 20290897 TI - The mechanism of menstruation. PMID- 20290898 TI - Vascularization of the cornea of the rat resulting from deficiency of B vitamins. PMID- 20290899 TI - Re-growth of nerve fibers in the spinal cord. PMID- 20290900 TI - The growth of the brain in the fetal dog. PMID- 20290901 TI - The ovary of the pika. PMID- 20290902 TI - Distribution of phosphatase and glycogen in the amphibian embryo. PMID- 20290903 TI - Development and chromosome number of the offspring of a tetraploid axolotl female mated with a diploid male. PMID- 20290904 TI - Pigmentation of adipose tissue as influenced by unsaturated fatty acids in vitamin E deficient rats. PMID- 20290906 TI - The excretion of fluorescein by the liver under normal and abnormal conditions, observed in vivo with the fluorescence microscope. PMID- 20290905 TI - Ceroid pigment in the testis of mice treated with estrogens. PMID- 20290907 TI - The acid phosphatase reaction in degenerating axons of certain sensory tracts. PMID- 20290908 TI - The plasmal reaction. PMID- 20290909 TI - Temperature influence during embryonic development in rats. PMID- 20290910 TI - The Golgi element in primitive erythroblasts of the 11-day rat embryo. PMID- 20290911 TI - Morphological evidence suggesting that human extrinsic eye muscles are phylogenetically relatively primitive. PMID- 20290912 TI - The lateral infracostal artery. PMID- 20290913 TI - Electrophoretic study of liver cytoplasmic proteins. PMID- 20290914 TI - The epicytes of mammalian lungs. PMID- 20290915 TI - An adrenergic link in the ovulatory mechanism of the rabbit. PMID- 20290916 TI - Effects of thiouracil, estradiol and testosterone propionate on the time appearance of the ossification centers of the rat. PMID- 20290917 TI - Malformations produced by sodium thiocyanate in the early development of the chick embryo. PMID- 20290918 TI - Cell counts in the anterior pituitary of the cat. PMID- 20290919 TI - Protargol used with the silver gelatin stain for nerve fibers. PMID- 20290920 TI - Some observations on the surface of some epithelial cells. PMID- 20290921 TI - Persistent pupillary membrane and hyaloid artery in the postnatal rat and mouse. PMID- 20290922 TI - An analysis of variations in the arteries and veins of the bronchopulmonary segments of 50 right upper lobes. PMID- 20290924 TI - Primitive carotid intersegmental arteries and the formation of the basilar in rabbit embryos injected while alive. PMID- 20290923 TI - Response of germinal epithelium of the mouse to thyroxin in the ovarian capsule. PMID- 20290925 TI - The rate of renewal in man of the water and sodium of the amniotic fluid as determined by tracer techniques. PMID- 20290926 TI - Progress of studies designed to determine whether the fetal hypophysis produces hormones that influence development. PMID- 20290927 TI - Follicular atresia in the ovaries of newts injected with diethylstilbestrol. PMID- 20290928 TI - Dermal characteristics in the presence of basal cell epitheliomas of human beings and after regression following treatment with tissue extracts. PMID- 20290929 TI - A simple method for obtaining photographic and cinematographic records of embryos and other small objects. PMID- 20290930 TI - A cell type possibly responsible for facultative salt excretion in the gills of Fundulus heteroclitus (a euryhaline fish). PMID- 20290931 TI - A histological study of eye abnormalities in the C57 black strain of mice. PMID- 20290932 TI - Two unusual anomalies in the same cadaver (Negro male, age 85 years). PMID- 20290933 TI - Boutons terminaux. PMID- 20290934 TI - Comparative pulmonic alveolar size in man, cat, rabbit, monkey, guinea pig, goat, dog, baboon, rat and mouse. PMID- 20290935 TI - Specialized argyrophilic (argentaffine?) cells in the anal canal of the rhesus monkey. PMID- 20290936 TI - An appendix epiploica resembling a vermiform appendix. PMID- 20290937 TI - Certain aspects of peripheral ganglion cells in Fundulus. PMID- 20290938 TI - Nerves of human dura mater. PMID- 20290939 TI - Electromyographic recordings from the m. biceps brachii during movements of the radioulnar, elbow, and shoulder joints. PMID- 20290940 TI - Changes in fiber tracts associated with inclusion bodies in nerve cells. PMID- 20290942 TI - On a human ovum of 17 days development. PMID- 20290941 TI - Autographic studies of the bony tissues with radioactive phosphorus and of the thyroid with radioactive iodine. PMID- 20290943 TI - The acid phosphatase content of normal autonomic neurons and its increase following section of the cell processes. PMID- 20290944 TI - A histological transformation of intestinal mucosa following administration of alloxan. PMID- 20290945 TI - A study of closure of the pleuropericardial and pleuroperitoneal canals in the human embryo. PMID- 20290946 TI - Effect of alloxan on the pancreatic islets of the guinea pig demonstrated with janus green. PMID- 20290947 TI - A colored moving picture used in teaching gross anatomy. PMID- 20290949 TI - Analgesia and anesthesia in obstetrics. PMID- 20290948 TI - Circulatory flow pattern in the bat's wing. PMID- 20290950 TI - Cell respiration and fermentation; a background for the study of narcotic action. PMID- 20290951 TI - Clinical use of metopryl as an anesthetic agent. PMID- 20290952 TI - A respiratory reflex originating from the thoracic wall of the dog. PMID- 20290953 TI - Deterioration of solutions of pentothal sodium. PMID- 20290954 TI - The used of curare in infants and children. PMID- 20290955 TI - Hypobaric pontocaine spinal anaesthesia; 1,640 consecutive cases. PMID- 20290957 TI - Variability in man and other primates. PMID- 20290956 TI - Tray for sterilizing laryngoscopes. PMID- 20290958 TI - Factorial analysis of body measurements. PMID- 20290959 TI - The relationship of strength to physique. PMID- 20290960 TI - A comparison of the percentages of stillbirths among single and plural births in the total, the white and the colored U.S. populations. PMID- 20290961 TI - A note on the duration of life of the ancient inhabitants of Anatolia. PMID- 20290962 TI - The number of vertebrae in the fetal Bantu sacrum. PMID- 20290963 TI - On the incidence of the foramen of Civinini and the porus crotaphitico buccinatorius in American whites and Negroes; observations on 2745 additional skulls. PMID- 20290967 TI - Studies on nonfruiting myxobacteria; Cytophaga johnsonae, n. sp., a chitindecomposing myxobacterium. PMID- 20290968 TI - Comparative distribution and possible pathogenicity of paracoli bact rium species in an area highly endemic for enteric infections. PMID- 20290970 TI - Penicillin; the effect of phenylacetic acid on penicillin production. PMID- 20290975 TI - The use of fragmented mycelial inoculum in the culture of fungi. PMID- 20290976 TI - The use of a polyvalent antiserum for preliminary identification of Salmonella cultures. PMID- 20290977 TI - Study of the utilization of some organic acids by Escherichia and Aerobacter. PMID- 20290978 TI - The preparation of silicic acid jellies for the cultivation of microorganisms. PMID- 20290979 TI - Advantages of incubation at 30 C for the study of staphylococci. PMID- 20290981 TI - Newcastle disease. PMID- 20290980 TI - Further studies on the effect of sterilizing glucose in culture media on growth of microorganisms; utilization of cystine by lactic acid bacteria. PMID- 20290982 TI - The real and the apparent bactericidal efficiencies of the quaternary ammonium compounds. PMID- 20290983 TI - Microbial fouling of zeolite water softeners. PMID- 20290984 TI - Phase variation in paracolon organisms. PMID- 20290985 TI - A capsule-dissolving factor. PMID- 20290986 TI - Familial nonspecific serologic reaction for syphilis. PMID- 20290987 TI - Inactivation of the germicidal action of quaternary ammonium compounds. PMID- 20290988 TI - Variation in tissue specificity of the Rous chicken sarcoma virus following growth of the tumor in the mammalian eye. PMID- 20290989 TI - Assimilation of acetate by yeast. PMID- 20290990 TI - Effect of specific antibody on transplanted mouse mammary cancer. PMID- 20290991 TI - Variation in molds; natural and induced. PMID- 20290992 TI - Some factors affecting the stability of type A (PR8) influenza virus. PMID- 20290993 TI - Microsporum audouini; the effect of yeast extract, thiamine, pyridoxine, and Bacillus weidmaniensis on the colony characteristics and macroconidial formation. PMID- 20290994 TI - A new Phytophthora causing root and collar rot of cinchona in Peru. PMID- 20290995 TI - Lagenidium humanum, a saprophyte isolated on dead human skin. PMID- 20290996 TI - Field notes on Tabanus nigrovittatus Macquart. PMID- 20290997 TI - Oxidation and reduction of indicators by Hydra. PMID- 20290998 TI - New facts on dependent, successive and conjugated spontaneous mutation. PMID- 20290999 TI - The nervous system and regeneration of the forelimb of adult Triturus; a further study of the importance of nerve number, including quantitative measurements of limb innervation. PMID- 20291000 TI - The nervous system and regeneration of the forelimb of adult Triturus; the relation between number of nerve fibers and surface area of amputation. PMID- 20291001 TI - [Not Available]. PMID- 20291002 TI - [Not Available]. PMID- 20291003 TI - [Not Available]. PMID- 20291005 TI - [Not Available]. PMID- 20291004 TI - [Not Available]. PMID- 20291006 TI - [Not Available]. PMID- 20291007 TI - The tilt-table test in neurocirculatory asthenia. PMID- 20291009 TI - [Not Available]. PMID- 20291008 TI - [Not Available]. PMID- 20291010 TI - L'ultra-microscopie statistique des virus. PMID- 20291011 TI - [Not Available]. PMID- 20291012 TI - [Not Available]. PMID- 20291013 TI - Glucose tolerance test in Ophidia and the effect of feeding on their glycemia. PMID- 20291014 TI - A comparison of assay results by biological and chemical methods on Digitalis purpurea and digitalin (crystalline). PMID- 20291015 TI - [Not Available]. PMID- 20291016 TI - A discussion of the basis of heart pain. PMID- 20291017 TI - [Not Available]. PMID- 20291018 TI - [Not Available]. PMID- 20291019 TI - [Not Available]. PMID- 20291020 TI - Carbohydrate metabolism in tissue homogenates. PMID- 20291021 TI - On the formation of fatty acids during the retting of flax. PMID- 20291022 TI - Purified rations and the requirement of folic acid for foxes. PMID- 20291023 TI - A comparison of plasma protein concentration, hemoglobin and hematocrit values determined by chemical methods and calculated from specific gravity. PMID- 20291024 TI - Trypsin inhibitor; determination and heat destruction of the trypsin inhibitor of soybeans. PMID- 20291025 TI - The biological availability of l-ascorbyl palmitate. PMID- 20291026 TI - Effect of dihydroxystearic acid on vitamin K synthesis by rats. PMID- 20291027 TI - Availability of vitamins in foods and food products; riboflavin balances with liquid milk, dried skimmed milk, and evaporated milk and the influence of succinyl sulfathiazole on such balances. PMID- 20291028 TI - Partial purification and properties of tomatin, an antibiotic agent from the tomato plant. PMID- 20291029 TI - The rate of anaerobic glycolysis of various hexoses in mammalian tissues. PMID- 20291030 TI - Direct estimation of leucine; application to milk and certain other foodstuffs. PMID- 20291032 TI - Reactions of non-enolizable ketones in sunlight. PMID- 20291031 TI - Oxidation-reduction potential of cytochrome c. PMID- 20291033 TI - The gas-phase photochemical decomposition of the simple aliphatic ketones. PMID- 20291034 TI - The Sandmeyer reaction. PMID- 20291035 TI - The pyrazines. PMID- 20291036 TI - A quantitative method for the estimation of the arsenoso group. PMID- 20291037 TI - 3-Amino-4-hydroxybenzenearsonous acid; salts and structural considerations. PMID- 20291038 TI - Structural determination of paraffin boiling points. PMID- 20291039 TI - Raman spectra of aqueous solutions of potassium thiocyanate. PMID- 20291041 TI - The synthesis of 2-hydroxy-17-equilenone. PMID- 20291040 TI - Oxidation potentials of some compounds related to vanillin. PMID- 20291042 TI - Studies in the quinoline series; synthesis of certain 4-substituted quinoline derivatives. PMID- 20291043 TI - 1-Gulo-D-talo-hepitol (beta-sedoheptitol) and its enantiomorph. PMID- 20291045 TI - An improved synthesis of di-lysine. PMID- 20291044 TI - Streptomycin; reduction and oxidation products of streptomycin and of streptobiosamine. PMID- 20291046 TI - The rate of movement of a chromatographic zone as a function of column position, initial concentration and initial volume. PMID- 20291047 TI - Studies on oxidation-reduction mechanism; potential humps and the equivalence change principle. PMID- 20291048 TI - Heats of adsorption on carbon black. PMID- 20291049 TI - Some 7-chloroquinolines patterned as open models of atebrin. PMID- 20291050 TI - t-Aminoalkyl derivatives of 2-aminothiazole. PMID- 20291051 TI - The constitution of acetylephedrine and acetyl-psi-ephedrine. PMID- 20291052 TI - Neovitamin A. PMID- 20291053 TI - The phase nature of beta sodium palmitate. PMID- 20291054 TI - Flavanones and related compounds; the reduction of some naturally-occurring flavones at the dropping mercury electrode. PMID- 20291056 TI - Some derivatives of 7-methylquinoline. PMID- 20291055 TI - Some derivatives of 6-methylquinoline. PMID- 20291057 TI - Periodate oxidation of phenols. PMID- 20291058 TI - The reaction of aminoalkyl halides with diphenylacetonitrile; the structure of amidone. PMID- 20291059 TI - The amino acid requirements of 23 lactic acid bacteria. PMID- 20291060 TI - Vitamin requirements of 23 lactic acid bacteria. PMID- 20291061 TI - The effect of carbohydrates on acid production by twenty-four lactic acid bacteria. PMID- 20291062 TI - The determination of d (-)- and l(+)-glutamic acid in protein hydrolysates. PMID- 20291063 TI - The determination of glycine in protein hydrolysates with Leuconostoc mesenteroides P-60. PMID- 20291064 TI - Kidney phosphatase in alimentary hyperglycemia and phlorhizin glycosuria; a dynamic mechanism for renal threshold for glucose. PMID- 20291065 TI - Immunological reactions between films of antigen and antibody molecules. PMID- 20291066 TI - The reaction of formaldehyde with proteins; participation of indole groups; gramicidin. PMID- 20291067 TI - Notes on the use of redistilled water and of amylose in the estimation of serum iodine. PMID- 20291068 TI - Dinicotinylornithine; a metabolite of nicotinamide in the chicken. PMID- 20291069 TI - The urinary excretion of a fat-mobilizing agent. PMID- 20291070 TI - A micromethod for the quantitative determination of the urinary coproporphyrin isomers (I and III). PMID- 20291071 TI - Variations of the individual blood plasma amino acid nitrogen level. PMID- 20291072 TI - The estimation of parathyroid hormone activity by its effect on serum inorganic phosphorus in the rat. PMID- 20291073 TI - A new preparation of the parathyroid hormone. PMID- 20291074 TI - The mechanism of action of the antifatty liver factor of the pancreas; a comparison of hydrolyzed and unhydrolyzed casein in the prevention of fatty livers of the completely depancreatized dog maintained with insulin. PMID- 20291075 TI - The rapid estimation of tyrothricin in fermentation liquors. PMID- 20291076 TI - Glycine and alanine concentrations of body fluids; experimental modification. PMID- 20291077 TI - The quantitative determination of ascorbic acid in small amounts of white blood cells and platelets. PMID- 20291078 TI - Relation of scurvy to glucose tolerance test, liver glycogen, and insulin content of pancreas of guinea pigs. PMID- 20291079 TI - The metabolism of phenoxyacetic acid, its homologues, and some monochlorophenoxyacetic acids; new examples of beta oxidation. PMID- 20291080 TI - Studies on cholinesterase; purification of the enzyme from electric tissue by fractional ammonium sulfate precipitation. PMID- 20291081 TI - The phosphorus-containing lipides of the carrot. PMID- 20291082 TI - Alloxan studies; the action of alloxan homologues and related compounds. PMID- 20291083 TI - The inhibitory action of naphthoquinones on respiratory processes. PMID- 20291084 TI - Amino acids excreted by mice fed incomplete proteins. PMID- 20291086 TI - The composition of flaxseed mucilage. PMID- 20291085 TI - The role of vitamin B6 in the synthesis of tryptophane from indole and anthranilic acid by Lactobacillus arabinosus. PMID- 20291087 TI - The estimation of basic organic compounds in biological material; general principles. PMID- 20291088 TI - The estimation of basic organic compounds in biological material; estimation of fluorescent compounds. PMID- 20291089 TI - The estimation of basic organic compounds in biological material; estimation by conversion to fluorescent compounds. PMID- 20291090 TI - The estimation of basic organic compounds in biological material; estimation by coupling with diazonium salts. PMID- 20291091 TI - The estimation of basic organic compounds in biological material; estimation by salt formation with methyl orange. PMID- 20291092 TI - The estimation of basic organic compounds in biological material; estimation by ultraviolet spectrophotometry. PMID- 20291093 TI - The plasma amino acid and amino nitrogen concentration during normal pregnancy, labor, and early puerperium. PMID- 20291094 TI - The composition of cardiolipin. PMID- 20291095 TI - The isolation of the 6-pyridone of N1-methylnicotinamide from urine. PMID- 20291096 TI - The action of tyrosinase on chymotrypsin, trypsin, and pepsin. PMID- 20291097 TI - A new synthesis of djenkolic acid. PMID- 20291098 TI - The deposition and antioxygenic behavior of alpha-, beta-, and gamma-tocopherols in rat fats. PMID- 20291099 TI - Streptomycin B, an antibiotically active constituent of streptomycin concentrates. PMID- 20291100 TI - The use of counter-current distribution for the analysis of streptomycin preparations. PMID- 20291101 TI - Tyrosine oxidation by livers from rats with a sulfasuxidine-induced pteroylglutamic acid deficiency. PMID- 20291102 TI - Synthesis of hippuric acid in liver homogenate. PMID- 20291103 TI - Inhibition of oxidation of succinic acid by structurally related sulfonic acids. PMID- 20291104 TI - Streptomycin; the linkage between streptidine and streptobiosamine. PMID- 20291105 TI - The enzymic synthesis of glutamine. PMID- 20291106 TI - The oxidation of beta-carotene in solution by oxygen. PMID- 20291107 TI - The configuration of heterocyclic compounds; preparation of phenoxstibines and resolution of 10-p-carboxyphenyl-2-methylphenoxstibine. PMID- 20291108 TI - The constitution of yeast ribonucleic acid; further studies on the nature of the carbohydrate radicals. PMID- 20291109 TI - Acid-base catalysis in non-aqueous solvents; the isomerisation of methyl mesityl oxide oxalate in chlorobenzene solution at 99 degrees. PMID- 20291110 TI - The catechins of green tea. PMID- 20291111 TI - The addition of thio-compounds to olefins; reactions of thioglycollic acid, thiophenol, and isopentanethiol. PMID- 20291112 TI - Synthetic antimalarials; the effect of variation of substituents in derivatives of mono- and di-alkylpyrimidines. PMID- 20291113 TI - Synthetic mydriatics. PMID- 20291114 TI - Researches in the phenanthridine series; further investigation of trypanocidal types. PMID- 20291115 TI - Viscosities of aqueous solutions on amino-acids, with some conductivity values. PMID- 20291116 TI - Strychnine and brucine; the preparation of neostrychnine and neobrucine. PMID- 20291117 TI - The search for chemotherapeutic amidines; two polyamidines. PMID- 20291118 TI - The search for chemotherapeutic amidines; phenanthridines. PMID- 20291119 TI - The search for chemotherapeutic amidines; pyridines. PMID- 20291120 TI - Solvent quenching of fluorescence. PMID- 20291121 TI - The place of yttrium and the application of ferricyanide precipitation in the rare-earth group; the purification of erbium. PMID- 20291123 TI - The sulphonation of some derivatives of eugenol. PMID- 20291122 TI - Synthesis of the monomethyl ethers of kaempferol, and the constitution of rhamnocitrin. PMID- 20291124 TI - 1:2:3:4-Tetrahydroisoquinaldinic acid. PMID- 20291125 TI - The pro-vitamin-A activity of mutatochrome. PMID- 20291126 TI - The action of benzene and aluminum chloride on tetrahalogenated phenols. PMID- 20291127 TI - Studies on Argentine plants; on the constitution of alpha-fagarine. PMID- 20291128 TI - Oximes of dialkylaminobutanediones. PMID- 20291129 TI - Preparation and polymerization of acrylic esters of olefinic alcohols. PMID- 20291130 TI - Reactions and analysis of beta-chloroethyl sulfide in water. PMID- 20291131 TI - Hydrolysis and oxidation of mustard gas and related compounds in aqueous solution. PMID- 20291132 TI - The hydrolysis and oxidation of beta-(beta-chloroethylthio)-ethyl ether and related compounds. PMID- 20291133 TI - Some reactions of 1,2-bis(beta-chloroethylthio)ethane. PMID- 20291134 TI - Some tertiary diamines derived from 1,2-bis(beta chloroethylthio)ethane. PMID- 20291135 TI - Some sulfonamide derivatives of 2-aminobenzimidazole. PMID- 20291136 TI - Sulfonamide preparations in glacial acetic acid. PMID- 20291137 TI - Nuclear substituted morphine derivatives. PMID- 20291138 TI - Phosphorus oxybromide as a brominating agent; bromopyrimidines. PMID- 20291139 TI - The synthesis of potential antimalarials; the preparation of methylated amides of taurine and their pantoyl derivatives. PMID- 20291140 TI - Some highly halogenated phenolic ethers as fungistatic compounds. PMID- 20291141 TI - The action of ethyl orthoformate on aniline and certain of its derivatives. PMID- 20291142 TI - Hydrolysis and chlorination of three beta-chloroe-thylamines. PMID- 20291143 TI - Biotin; synthesis of dl-epibiotin. PMID- 20291144 TI - Biotin; penthiane-3,4-dicarboxylic acid. PMID- 20291145 TI - Condensation of aromatic aldehydes with alpha-picoline methiodide. PMID- 20291146 TI - Analgesic studies; beta-ethyl and beta-isopropylamine derivatives of pyridine and thiazole. PMID- 20291147 TI - Isolation and purification of neopine. PMID- 20291148 TI - Some reactions of neopine. PMID- 20291149 TI - The limitations of orthodontic treatment; mixed dentition diagnosis and treatment. PMID- 20291150 TI - The correction of mandibular subluxation. PMID- 20291151 TI - The healing of extraction wounds in the presence of retained root remnants and bone fragments. PMID- 20291152 TI - Some clinical observations concerning noma. PMID- 20291153 TI - Premedication by co-medication in local anesthesia. PMID- 20291154 TI - Apicoectomy. PMID- 20291155 TI - Root amputation; a definitive surgery. PMID- 20291156 TI - Master metal facial cast for swaging lead masks in the treatment of carcinoma of the skin of the face. PMID- 20291157 TI - Erythema multiforme exudativum (Steven s-Johnson syndrome). PMID- 20291158 TI - A resume of the development of penicillin and sulfonamides, and their application to dental surgery. PMID- 20291159 TI - Ankylosis, synovitis and arthritis. PMID- 20291160 TI - The newer knowledge of hygiene in diet. PMID- 20291161 TI - Description of a new type of interchangeable porcelain and acrylic facing for crown and bridgework. PMID- 20291162 TI - The plastics; with special emphasis on the use of acrylics in the construction of jacket crowns, bridgework and partial dentures. PMID- 20291164 TI - The pharyngeal gasway; its use in exodontia. PMID- 20291163 TI - Some psychosomatic aspects of medicine. PMID- 20291165 TI - Surgery of the mouth and jaws. PMID- 20291166 TI - Impacted and aberrant teeth. PMID- 20291167 TI - Diagnostic oral roentgenology. PMID- 20291168 TI - Practical dental assisting. PMID- 20291169 TI - Conventional eating habits and dental caries. PMID- 20291170 TI - The integration of the basic sciences in clinical operative dentistry. PMID- 20291171 TI - The application of pharmacology in clinical operative dentistry. PMID- 20291172 TI - Does the present status of clinical investigation indicate the advisability of pulp capping? PMID- 20291174 TI - Fact and hypothesis in the teaching of periodontology. PMID- 20291173 TI - What constitutes an adequate requirement in clinical operative dentistry? PMID- 20291175 TI - The dental curriculum in American universities. PMID- 20291176 TI - [Not Available]. PMID- 20291177 TI - [Not Available]. PMID- 20291178 TI - [Not Available]. PMID- 20291179 TI - [Not Available]. PMID- 20291181 TI - [Not Available]. PMID- 20291180 TI - [Not Available]. PMID- 20291182 TI - [Not Available]. PMID- 20291183 TI - [Not Available]. PMID- 20291184 TI - The cell, 1946. PMID- 20291185 TI - Blood sedimentation rate; technical consideration and clinical evaluation. PMID- 20291186 TI - Ringworm. PMID- 20291187 TI - Accuracy as a quality essential to the medical technologist. PMID- 20291188 TI - The significance of the antivitamins in nutrition. PMID- 20291189 TI - Unrestricted diet in the treatment of juvenile diabetes. PMID- 20291190 TI - A practical approach to nutrition education for children. PMID- 20291191 TI - Research in nutrition education. PMID- 20291192 TI - Recent trends in frozen foods. PMID- 20291193 TI - Palatability and vitamin retention in large-scale food preparation of dehydrated sulphited potato strips. PMID- 20291194 TI - Some effects of methionine on the utilization of nitrogen in the adult dog. PMID- 20291195 TI - The effect of methionine upon the urinary nitrogen in men at normal and low levels of protein intake. PMID- 20291196 TI - Amino acids in nitrogen metabolism with particular reference to the role of methionine. PMID- 20291197 TI - Covitamin studies; effect of tocopherol supplementation on the output of vitamin A, carotene, and fat by dairy cows. PMID- 20291198 TI - Some observations on the nutritional value of dialyzed whey solids. PMID- 20291199 TI - Nitrogen retention studies on rats, dogs and man; the effect of adding methionine to an enzymic case in hydrolystate. PMID- 20291200 TI - The conjoint effects of varied intakes of thiamine and vitamin A on rats. PMID- 20291201 TI - The value of meat and peas, alone or in combination, as a source of protein for growth. PMID- 20291202 TI - Tissue reserves of ascorbic acid in normal adults on three levels of intake. PMID- 20291203 TI - Some observations on the state of nutrition in the Union of South Africa. PMID- 20291204 TI - The medical approach to the problem of malnutrition. PMID- 20291205 TI - Clinical aspects of malnutrition. PMID- 20291207 TI - Surgery and nutrition. PMID- 20291206 TI - The role of the proteins in under-nutrition. PMID- 20291208 TI - The internal storage of foodstuffs with special reference to bony tissue as the body's mineral bank. PMID- 20291209 TI - Certain aspects of nutrition and the eye. PMID- 20291210 TI - Remedies for malnutrition. PMID- 20291211 TI - Some nutritional problems in the rural Bantu. PMID- 20291212 TI - The significance of animal nutrition and health to that of the human population in the Union. PMID- 20291213 TI - The problem of supplementing the African diet examined in the light of current concepts of nutrition. PMID- 20291214 TI - Nutrition in pregnancy. PMID- 20291215 TI - The application of the findings of the National Health Commission in planning for the future of the problem. PMID- 20291216 TI - [Not Available]. PMID- 20291218 TI - [Not Available]. PMID- 20291217 TI - [Not Available]. PMID- 20291220 TI - Anaesthesia in the aged. PMID- 20291219 TI - On precursors of gastric carcinoma. PMID- 20291221 TI - The effect of age on the leukocyte count; a comparison of white blood cell counts in aged and young individuals, with special reference to the response to infection. PMID- 20291222 TI - Nutritional aspects of aging. PMID- 20291223 TI - Cutaneous hypersensitivity reactions to penicillin in the aged. PMID- 20291224 TI - Physical fitness and work capacity of older men. PMID- 20291225 TI - Hypercholesterolemia and atheromatous disease in premature aging. PMID- 20291226 TI - The fibrous nature of the human cervix, and its relation to the isthmic segment in gravid and nongravid uteri. PMID- 20291227 TI - The amniotic duct as the key structure in the determination of the direction of growth of the human placenta and its orientation in the uterus. PMID- 20291228 TI - The clinical significance of Rh antibodies (Rh agglutinins and blocking antibodies) in the sera of Rh-negative mothers; a study of 179 cases. PMID- 20291229 TI - False positive Rh typing obtained with commercial anti-Rho serum. PMID- 20291230 TI - The effect of wartime starvation in Holland upon pregnancy and its product. PMID- 20291231 TI - Selective cytology smear for diagnosis of cancer. PMID- 20291232 TI - Operation for the cure of incontinence of urine in the female. PMID- 20291234 TI - The time of ovulation. PMID- 20291233 TI - Irregular shedding of the endometrium. PMID- 20291235 TI - Placental metabolism of vitamin C; normal placental content. PMID- 20291236 TI - The possible etiologic significance of thrombosis of a placental vein on the mechanism of placental infarction and associated toxemia of pregnancy. PMID- 20291237 TI - Podophyllin treatment of soft papillomas of the female urethra. PMID- 20291238 TI - Uterine adenomyosis; incidence, symptoms, and pathology in 1,856 hysterectomies. PMID- 20291239 TI - A general survey of maternal care in a Navy hospital. PMID- 20291240 TI - Metastatic chorionepithelioma of the lung treated by lobectomy. PMID- 20291241 TI - Preliminary clinical report on a new synthetic estrogen, meprane. PMID- 20291243 TI - The dangers of the intracervical pessary as a contraceptive device. PMID- 20291242 TI - Meningitis following continuous caudal anesthesia. PMID- 20291244 TI - Dysgerminoma and pregnancy. PMID- 20291245 TI - Bilateral dermoid cysts, uterine fibroids, and pregnancy. PMID- 20291246 TI - Successful repair of a vesicovaginal fistula complicating carcinoma of the cervix. PMID- 20291247 TI - Genital tuberculosis with atresia of the vagina and amenorrhea. PMID- 20291248 TI - Coexisting different tumors of the ovaries. PMID- 20291249 TI - Cranial deformation in the reign of Akhnaton. PMID- 20291250 TI - William Osler and Howard A. Kelly, physicians, medical historians, friends, as revealed by nineteen letters from Osler to Kelly. PMID- 20291251 TI - Ignaz Philipp Semmelweis, (1818-1865); an annotated bibliography. PMID- 20291252 TI - Human multiple births. PMID- 20291254 TI - The surgical management of peptic ulcers in railway employees. PMID- 20291253 TI - The effect of administering a vitamin supplement, in capsules, to groups of workers in the steel industry. PMID- 20291256 TI - Systematizing accident investigation. PMID- 20291255 TI - The diagnosis and management of acute head injuries. PMID- 20291257 TI - Early treatment of ocular injuries. PMID- 20291258 TI - Medical departments in small plants. PMID- 20291259 TI - The post-cholecystectomy syndrome. PMID- 20291260 TI - Industrial sanitation. PMID- 20291261 TI - First aid for chemical eye injuries. PMID- 20291262 TI - Amputation of the leg. PMID- 20291263 TI - Mass immunization against influenza types A and B in an industrial plant. PMID- 20291265 TI - The teacher as counselor in marriage education. PMID- 20291264 TI - BENZOL. PMID- 20291266 TI - Married veterans are good students. PMID- 20291267 TI - The role of the library in family life education. PMID- 20291268 TI - Clinical features of patent ductus arteriosus with special reference to cardiac murmurs. PMID- 20291269 TI - Infectious hepatitis; clinical and laboratory features of 295 cases. PMID- 20291270 TI - Liver dysfunction in rheumatic heart disease; preliminary report. PMID- 20291271 TI - The treatment of pneumococcic pneumonia with oral and intramuscular penicillin. PMID- 20291272 TI - Some pharmacological and clinical experiences with dimethylaminoethyl benzhydryl ether hydrochloride (benadryl). PMID- 20291273 TI - The intravenous use of human ascitic fluid in shock, nephrosis and allied conditions. PMID- 20291274 TI - Renal excretory function and diet in diabetes insipidus. PMID- 20291275 TI - Observations on the treatment of carcinoma of the prostate by orchidectomy. PMID- 20291276 TI - The femoral bone marrow cells of the albino rat. PMID- 20291277 TI - Postpartum blood; its clotting mechanism and relationship to the peripheral blood picture. PMID- 20291278 TI - The effect of circulatory factors on the bromsulphalein test in liver disease. PMID- 20291279 TI - Menopausal hypertension; a critical study. PMID- 20291280 TI - Amylase levels during mumps; the findings in blood and saliva. PMID- 20291281 TI - The failure of massive salicylate therapy to suppress the inflammatory reaction in rheumatic fever. PMID- 20291282 TI - Changes in personality appraisal associated with a restricted intake of B vitamins and protein. PMID- 20291283 TI - Virus pyogen and virus pyogen photosensitivity relationships in cutaneous disease. PMID- 20291284 TI - Throat medication; a survey of current trends. PMID- 20291285 TI - Factors in the control of capillary and venous pressure demonstrated by a schema. PMID- 20291286 TI - A study of the factors controlling the differentiation of Mauthner's cell in Amblystoma. PMID- 20291287 TI - The Brooklyn Hospital during the war years. PMID- 20291288 TI - The prevention of cardiovascular syphilis. PMID- 20291289 TI - Congenital stenosis of the pulmonary valve in the absence of septal defects. PMID- 20291290 TI - The 79th General Hospital; a narrative. PMID- 20291291 TI - Ectopic decidua in the cecum report of a case presenting an acute inflammatory lesion at the site of an ectopic decidual focus. PMID- 20291293 TI - The syndrome of compression of the sixth cervical spinal nerve. PMID- 20291292 TI - [Carcinoma of the stomach, intrinsic, with metastases to the liver]. PMID- 20291294 TI - Carcinoma of the prostate; a symposium. PMID- 20291295 TI - Carcinoma of the prostate; determination of the acid phosphatase of the blood serum as an aid in diagnosis. PMID- 20291296 TI - Carcinoma of the prostate; radiologic considerations. PMID- 20291297 TI - Carcinoma of the prostate; neurologic disturbances resulting from metastases. PMID- 20291298 TI - Carcinoma of the prostate; pathologic observations. PMID- 20291299 TI - [Myelogenous leukemia]. PMID- 20291301 TI - Urinary calculi. PMID- 20291300 TI - Treatment of erythroblastosis by exsanguination transfusion. PMID- 20291302 TI - Studies on the protein metabolism of the infant; the comparative biological value of some milk protein preparations. PMID- 20291303 TI - Studies on the protein metabolism of infants; tryptophane requirement of the infant. PMID- 20291304 TI - The antipellagra action of N1-methylnicotinamide. PMID- 20291305 TI - Disappearance time of Treponema pallidum from lesions of early syphilis following administration of crystalline penicillin G. PMID- 20291307 TI - Investigation and treatment of infertility. PMID- 20291306 TI - The prevention of pyloric ligation-induced ulcers of the gastric rumen of rats by transabdominal vagotomy; a preliminary report. PMID- 20291308 TI - Certain peculiarities of brain metabolism. PMID- 20291309 TI - The use of isuprel for the management of bronchial asthma. PMID- 20291310 TI - Immunity to virus disease. PMID- 20291311 TI - The evolution of the New England Medical Center. PMID- 20291312 TI - Streptomycin in pulmonary tuberculosis. PMID- 20291313 TI - An approach to the diagnosis and treatment of gout. PMID- 20291315 TI - Carcinoma in situ. PMID- 20291314 TI - Homologous serum hepatitis in civilian practice. PMID- 20291316 TI - The excretion of water. PMID- 20291320 TI - Immunization against diphtheria and whooping cough. PMID- 20291321 TI - Notes on diagnostic intradermal tests. PMID- 20291322 TI - The doctor and his relations with the police and the coroner. PMID- 20291323 TI - The treatment of veneral disease in general practice. PMID- 20291324 TI - Differential diagnosis of common external diseases of the eye met with in general practice. PMID- 20291325 TI - Varicose veins and varicose ulcers. PMID- 20291326 TI - The indications for radiotherapy and its value in general practice. PMID- 20291327 TI - Rheumatoid arthritis. PMID- 20291328 TI - Blood dyscrasias. PMID- 20291329 TI - Differential diagnosis of lower motor neurone diseases. PMID- 20291330 TI - Artificial pneumothorax and some of its pitfalls. PMID- 20291331 TI - Occipito-posterior positions. PMID- 20291332 TI - Some practical aspects of the management of pregnancy. PMID- 20291333 TI - Management of measles and whooping-cough and their sequelae. PMID- 20291334 TI - Difficulties associated with breast feeding. PMID- 20291336 TI - 17-Ketosteroids; a review of the literature. PMID- 20291335 TI - Penicillin in tetanus with an analysis of the spinal fluid in tetanus. PMID- 20291337 TI - [HYDATID mole]. PMID- 20291338 TI - Treatment of acute sulfadiazine anuria by continuous peritoneal lavage; a case report. PMID- 20291339 TI - Observations on the behavior of myoepithelial cells in the human breast. PMID- 20291340 TI - Chronic vasomotor rhinitis in pregnancy. PMID- 20291341 TI - Toxic reactions to local anesthetics. PMID- 20291342 TI - [CESAREAN section; case report]. PMID- 20291343 TI - ONE hundredth anniversary of the first administration of anesthetic ether. PMID- 20291344 TI - Surgery before anesthesia. PMID- 20291345 TI - Dr. William T. G. Morton and ether. PMID- 20291346 TI - Anesthesiology today and tomorrow. PMID- 20291347 TI - Subdiaphragmatic vagotomy; indications and technic. PMID- 20291348 TI - Hemorrhagic diabetic retinitis; a method of treatment based on the elevation of plasma albumin by diet. PMID- 20291349 TI - Neoplasms of the small intestine. PMID- 20291350 TI - The use of curare and pentothal sodium in endoscopy. PMID- 20291351 TI - Gastrocolic fistula; a new concept of pathologic physiology; mechanism of production of the syndrome. PMID- 20291353 TI - Differential diagnosis between cerebral and cerebellar denegeration and brain tumor. PMID- 20291352 TI - Skeletal changes in chronic fluorine intoxication; report of a case. PMID- 20291354 TI - Intra-arterial transfusion in the treatment of experimental hemorrhagic shock. PMID- 20291355 TI - Hypospadias. PMID- 20291356 TI - Brain tumor with long survival of patient; report of a case. PMID- 20291357 TI - Brief reviews in clinical medicine. PMID- 20291358 TI - Diabetes mellitus and gall bladder disease. PMID- 20291359 TI - Mesenteric fibrosarcoma; report of a case. PMID- 20291360 TI - Metastatic carcinoma of the lung simulating heart failure. PMID- 20291361 TI - Successful immunization procedures. PMID- 20291362 TI - Two years medical work in the Northern Frontier District, Kenya Colony. PMID- 20291363 TI - The experimental control of mosquito breeding in rice fields in Nyanza Province, Kenya, by intermittent irrigation and other methods. PMID- 20291364 TI - The technique of D. D. T. impregnation of native huts. PMID- 20291365 TI - A mosquito survey of Mahe, Seychelles. PMID- 20291366 TI - The description of a new mosquito from the Seychelles. PMID- 20291367 TI - Aedes control at Lamu. PMID- 20291368 TI - A preliminary note on the sylvan mosquitos of Gede. PMID- 20291369 TI - The description of a new Anopheles of the Myzorhynchus series from Madagascar with notes on its systematic position in relation to the Ethiopian species of this group. PMID- 20291371 TI - Simuliidae of Kenya. PMID- 20291370 TI - A new blood spirochaete in the grivet monkey; Ceropithecus aethiops. PMID- 20291372 TI - A giant fruit bat from north Kavirondo. PMID- 20291373 TI - The care and maintenance of laboratory animals and arthropod vectors of disease. PMID- 20291374 TI - The necessity of animal experimentation for progress in medicine. PMID- 20291375 TI - Tumors of the anterior abdominal wall. PMID- 20291376 TI - Peptic ulcer complicated by hemorrhage; a report of 36 cases. PMID- 20291377 TI - Ocular allergy to tuberculosis. PMID- 20291378 TI - Spondylitis due to undulant fever. PMID- 20291379 TI - Deceptive pyelogram. PMID- 20291380 TI - Atypical angina pectoris; mechanism, importance and differential diagnosis. PMID- 20291381 TI - [Carcinoma of the descending colon with subphrenic abscess perforating into a bronchus]. PMID- 20291382 TI - [Not Available]. PMID- 20291384 TI - [Not Available]. PMID- 20291383 TI - [Not Available]. PMID- 20291385 TI - [Not Available]. PMID- 20291386 TI - [Not Available]. PMID- 20291387 TI - [Not Available]. PMID- 20291388 TI - [Not Available]. PMID- 20291389 TI - [Not Available]. PMID- 20291390 TI - [Not Available]. PMID- 20291391 TI - [Not Available]. PMID- 20291392 TI - [Not Available]. PMID- 20291393 TI - [Not Available]. PMID- 20291394 TI - [Not Available]. PMID- 20291395 TI - [Not Available]. PMID- 20291396 TI - [Not Available]. PMID- 20291397 TI - [Not Available]. PMID- 20291398 TI - [Not Available]. PMID- 20291401 TI - [Not Available]. PMID- 20291400 TI - [Not Available]. PMID- 20291399 TI - [Not Available]. PMID- 20291402 TI - [Not Available]. PMID- 20291403 TI - [Not Available]. PMID- 20291404 TI - [Not Available]. PMID- 20291405 TI - [Not Available]. PMID- 20291406 TI - [Not Available]. PMID- 20291407 TI - [Not Available]. PMID- 20291409 TI - [Not Available]. PMID- 20291408 TI - [Not Available]. PMID- 20291412 TI - [Not Available]. PMID- 20291411 TI - [Not Available]. PMID- 20291410 TI - [Not Available]. PMID- 20291413 TI - [Not Available]. PMID- 20291414 TI - [Not Available]. PMID- 20291415 TI - [Not Available]. PMID- 20291416 TI - [Not Available]. PMID- 20291417 TI - [Not Available]. PMID- 20291418 TI - [Not Available]. PMID- 20291419 TI - [Not Available]. PMID- 20291420 TI - [Not Available]. PMID- 20291421 TI - [Not Available]. PMID- 20291422 TI - [Not Available]. PMID- 20291423 TI - [Not Available]. PMID- 20291424 TI - [Not Available]. PMID- 20291425 TI - [Not Available]. PMID- 20291426 TI - [Not Available]. PMID- 20291427 TI - [Not Available]. PMID- 20291428 TI - [Not Available]. PMID- 20291429 TI - [Not Available]. PMID- 20291430 TI - [Not Available]. PMID- 20291432 TI - [Not Available]. PMID- 20291431 TI - [Not Available]. PMID- 20291433 TI - [Not Available]. PMID- 20291434 TI - Tropical ulcer in the Hissar district of the Punjab. PMID- 20291435 TI - Ten cases of typhus in civilians in Calcutta. PMID- 20291436 TI - Observations on the treatment of 25 cases of kala-azar with stibatin (sodium antimony gluconate). PMID- 20291437 TI - Activation of the human system in filariasis. PMID- 20291438 TI - Observations on eosinophilic lung. PMID- 20291439 TI - Leukaemoid reaction after blood transfusion. PMID- 20291440 TI - Diagnosis of infective hepatitis in its prodromal and invasion stages. PMID- 20291441 TI - Ocular manifestations of avitaminosis in adults. PMID- 20291442 TI - Penetrating injury in a pregnant woman. PMID- 20291443 TI - A case of brucellosis (abortus fever). PMID- 20291444 TI - Mistaken diagnoses; chocolate cysts of the ovary; dermoid cyst of the lung. PMID- 20291445 TI - Studies in the health problems of a rural community in western Bengal; population problems. PMID- 20291446 TI - The state of nutrition and physical development of school children in Hyderabad State. PMID- 20291447 TI - The action of nicotinic acid on the heart of Rana tigrina. PMID- 20291448 TI - Serological reactions in tropical eosinophilia. PMID- 20291449 TI - Some experiments on toque monkeys with tyroglyphid mites. PMID- 20291450 TI - Regional enteritis (Crohn's disease); a case with multiple jejunal strictures. PMID- 20291451 TI - Effect of blood donation on the haemopoietic system. PMID- 20291452 TI - Poisonous foodgrain; wheat mixed with Lolium temulentum. PMID- 20291453 TI - Normal blood sedimentation rate and other haematological values in the Punjab. PMID- 20291454 TI - Amoebic abscess of liver bursting into pericardial cavity. PMID- 20291455 TI - Neonatal deaths and still births in Bombay. PMID- 20291456 TI - A new oil medium for enhancement of growth of the Malassezia and subsequent study of serological reactions and pathogenicity. PMID- 20291457 TI - Use of penicillin in rat and human leprosy. PMID- 20291458 TI - Occurrence of Bact. alcaligenes sp. in duck eggs. PMID- 20291459 TI - A case of Petit's eventration of the diaphragm. PMID- 20291460 TI - Transmission of kala-azar in India; the case against the sandfly; a reply. PMID- 20291461 TI - A note on cholera outbreaks (1944-45) in the Singur Health Centre area, Bengal, with special reference to control measures. PMID- 20291462 TI - Sulphapyridine anuria including histopathological examination of kidney in one case. PMID- 20291463 TI - Enicostema littorale Blume in malaria. PMID- 20291464 TI - Undulant fever in Bombay. PMID- 20291465 TI - Cervical rib syndrome, with a case record. PMID- 20291466 TI - Is second attack of diphtheria possible? PMID- 20291467 TI - Tropical eosinophilia. PMID- 20291468 TI - Observations on the interpretation of the hippuric acid synthesis test of liver function. PMID- 20291469 TI - Dissecting aneurysm of the aorta; a case report and a review of 133 cases. PMID- 20291470 TI - Amoebic hepatitis and associated pericarditis. PMID- 20291471 TI - An unusual case of snake bite; intravenous sodium sulphate treatment of threatened uraemia. PMID- 20291472 TI - Ocular complications in malaria; a case of dendritic ulcer. PMID- 20291473 TI - Penicillin in typhoid fever. PMID- 20291474 TI - A case of pulmonary amoebiasis. PMID- 20291475 TI - Thiouracil. PMID- 20291476 TI - Malnutrition in Bengal. PMID- 20291477 TI - Note on diet surveys carried out in the central Provinces and Berar. PMID- 20291478 TI - Some aspects of clinical malnutrition. PMID- 20291480 TI - Food. PMID- 20291479 TI - Nutritional requirements. PMID- 20291481 TI - Value of soya-bean. PMID- 20291482 TI - Defects in the present public health propaganda. PMID- 20291483 TI - A case of acute emetine poisoning. PMID- 20291484 TI - The Sind leprosy control bill for diseased immigrants. PMID- 20291485 TI - Eosinophilic lungs. PMID- 20291486 TI - Psychological aspects of riots, killing and carnage. PMID- 20291487 TI - Local therapy of shark-liver oil in nyctalopia. PMID- 20291489 TI - The kiss; its advantage and disadvantage. PMID- 20291488 TI - Eye troubles in old age. PMID- 20291490 TI - Importance of vaccination and nursing. PMID- 20291491 TI - A case of aconite poisoning. PMID- 20291492 TI - The management of jaundiced patients; consideration of the indications for surgical treatment. PMID- 20291493 TI - Intravenous therapy of cirrhosis of the liver. PMID- 20291494 TI - Propylthiouracil in thyrotoxicosis; observations on 54 patients. PMID- 20291495 TI - Typhus fever in the United States Army following immunization; incidence, severity of the disease, modification of the clinical course and serologic diagnosis. PMID- 20291496 TI - The value of endotracheal intubation. PMID- 20291497 TI - Esophageal leiomyoma; report of a successful resection. PMID- 20291499 TI - Aggravation of a gastric ulcer following dorsolumbar sympathectomy. PMID- 20291498 TI - Penicillin therapy of gonococcic endocarditis of the pulmonary valve. PMID- 20291500 TI - The successful treatment of acute renal failure by peritoneal irrigation. PMID- 20291501 TI - Orthoptics. PMID- 20291502 TI - Urologic complications. PMID- 20291503 TI - Adaptability of the supravital technique to experimental and clinical problems. PMID- 20291504 TI - The blood clotting mechanism; the clinical anticoagulants. PMID- 20291505 TI - Hemoflagellates. PMID- 20291506 TI - Psychological effects of the war on British children. PMID- 20291507 TI - Tuberculosis control activities of the Arkansas State Board of Health. PMID- 20291508 TI - A consideration of the surgical complications of amebiasis of the colon and rectum. PMID- 20291509 TI - Modern concepts of cardio-vascular disease. PMID- 20291510 TI - Trends in tuberculosis control procedures. PMID- 20291511 TI - Health service areas. PMID- 20291512 TI - Preventive medicine; a new approach. PMID- 20291513 TI - Calcification of the pleura. PMID- 20291514 TI - The comparative value of pentothal sodium, curare, and magnesium sulfate for the modification of metrazol convulsions. PMID- 20291515 TI - The effect of various suture materials in wound healing. PMID- 20291516 TI - The importance of accurate diagnosis in tuberculosis. PMID- 20291517 TI - Responsibility of the physician in the education of the tuberculous. PMID- 20291518 TI - The antibacterial approach to the treatment of tuberculosis. PMID- 20291519 TI - TUBERCULOSIS among college students. PMID- 20291520 TI - Incidence of tuberculosis in student nurses. PMID- 20291521 TI - Tuberculosis in Mexican agricultural laborers. PMID- 20291522 TI - The therapy of hemorrhage. PMID- 20291523 TI - Vitamin D2 in the treatment of cutaneous tuberculosis. PMID- 20291524 TI - Bronchiogenic carcinoma of the lung. PMID- 20291525 TI - The fenestration operation for deafness. PMID- 20291526 TI - Acute and subacute yellow atrophy of liver; report of three cases with necropsy. PMID- 20291527 TI - Cystic and caseous tuberculosis of multiple bones; case report. PMID- 20291528 TI - [Necrotizing pharyngitis]. PMID- 20291529 TI - Founder of modern tuberculosis treatment, Edward Livingston Trudeau. PMID- 20291530 TI - The sword and the plough share [the mustards]. PMID- 20291531 TI - Physiological problems in the treatment of heart disease. PMID- 20291532 TI - The operability of malignant pulmonary neoplasms with special reference to cancer of the lung. PMID- 20291533 TI - The effect of atabrin on auricular fibrillation and supraventricular tachycardia in man. PMID- 20291534 TI - Tuberculous fecal fistula following pelvic surgery. PMID- 20291535 TI - Echinococcus alveolaris infection of the human liver. PMID- 20291536 TI - Cardiospasm. PMID- 20291537 TI - A suggestion for the treatment of chronic sinus disease. PMID- 20291538 TI - Centenaries of 1946. PMID- 20291539 TI - Some rules for the employment of local analgesia in the treatment of somatic pain. PMID- 20291540 TI - Heterospecific pregnancy; the Rh factor and repeated miscarriages. PMID- 20291541 TI - Spontaneous rupture of the spleen in malaria. PMID- 20291542 TI - Dementia paralytica occurring in chronic schizophrenia. PMID- 20291543 TI - The treatment of thyreotoxicosis by concurrent administration of thiouracil and iodine. PMID- 20291544 TI - Asiatic schistosomiasis; an outbreak in the Royal Australian Air Force. PMID- 20291545 TI - Leon Daudet; some extracts from his memoirs dealing with French medicine in the eighties and nineties. PMID- 20291546 TI - Intracranial damage in the newly born. PMID- 20291547 TI - The present position of allergy. PMID- 20291548 TI - Two cases of narcolepsy. PMID- 20291549 TI - Puzzling foot symptoms from abnormal nerve distribution. PMID- 20291550 TI - Herpes zoster with associated muscle paralysis. PMID- 20291551 TI - [Liver puncture]. PMID- 20291552 TI - Asthma and some psychophysical interrelations. PMID- 20291554 TI - On the treatment of placenta praevia. PMID- 20291553 TI - Penicillin in the treatment of discharge from the middle ear. PMID- 20291555 TI - Anaphylactic purpura following intramuscular penicillin therapy. PMID- 20291557 TI - Peptic ulcer. PMID- 20291556 TI - Meningitis; isolation of an organism resembling Neisseria catarrhalis from cerebro-spinal fluid; report of a case. PMID- 20291558 TI - Prevention and modern treatment of eclampsia. PMID- 20291559 TI - The diagnosis and treatment of lung abscess. PMID- 20291560 TI - Problems of infection in the nurseries. PMID- 20291561 TI - A case of congenital absence of the vagina. PMID- 20291562 TI - Progress in cancer control in the United States. PMID- 20291563 TI - Activities of the National Cancer Institute and the National Advisory Cancer Council. PMID- 20291564 TI - [Not Available]. PMID- 20291565 TI - [Carcinoma of the large bowel]. PMID- 20291567 TI - Menopausal bleeding. PMID- 20291566 TI - Modern trends in burn therapy. PMID- 20291568 TI - Lumbar sympathectomy in the treatment of peripheral vascular diseases with case report of results in Buerger's disease. PMID- 20291569 TI - Pheumococcus peritonitis; report of three cases, two treated with penicillin. PMID- 20291570 TI - The diagnosis of pernicious anemia. PMID- 20291571 TI - Surgical management of vascular injuries in combat. PMID- 20291572 TI - Fatty infiltration and hepatic degeneration. PMID- 20291573 TI - The dangers associated with nodular goiter. PMID- 20291574 TI - Roentgenologic findings in atypical pneumonia. PMID- 20291575 TI - Treatment of hepatic cirrhosis. PMID- 20291576 TI - The problem of social medicine; equilibrating the distribution and technology of medical care. PMID- 20291577 TI - The teaching hospital's service to the public. PMID- 20291578 TI - Acute yellow atrophy following cinchophen administration; report of a case. PMID- 20291579 TI - Leukemia cutis; report of a case, with a discussion of treatment by the use of hormones. PMID- 20291580 TI - Effects of protein deficiency on the pregnant woman and fetus and on the infant and child. PMID- 20291581 TI - [Benign giant-cell tumor of coccyx and sacrum]. PMID- 20291582 TI - [Fibromyxosarcoma]. PMID- 20291583 TI - Socialized medicine. PMID- 20291584 TI - Ligation of the vena cava; a critical evaluation based on a study of 22 cases. PMID- 20291585 TI - The unstable colon, its role as a precursor to diverticulosis. PMID- 20291586 TI - Actinomycosis; a report of twelve cases with special reference to a mediastinal case. PMID- 20291587 TI - Multiple operative procedures in a case of von Recklinghausen's disease. PMID- 20291588 TI - Traumatic rupture of the pancreas; case report. PMID- 20291589 TI - An evaluation of the psychogenic factor in peptic ulcer. PMID- 20291590 TI - New methods of hemostasis. PMID- 20291591 TI - Preventive medicine in the cancer field. PMID- 20291592 TI - [Not Available]. PMID- 20291593 TI - [Not Available]. PMID- 20291594 TI - [Not Available]. PMID- 20291595 TI - [Not Available]. PMID- 20291596 TI - [Not Available]. PMID- 20291597 TI - [Not Available]. PMID- 20291598 TI - [Not Available]. PMID- 20291599 TI - [Not Available]. PMID- 20291600 TI - [Not Available]. PMID- 20291601 TI - [Not Available]. PMID- 20291602 TI - [Not Available]. PMID- 20291603 TI - [Not Available]. PMID- 20291604 TI - [Not Available]. PMID- 20291605 TI - [Not Available]. PMID- 20291606 TI - [Not Available]. PMID- 20291607 TI - [Not Available]. PMID- 20291608 TI - [Not Available]. PMID- 20291609 TI - [Not Available]. PMID- 20291610 TI - [Not Available]. PMID- 20291611 TI - [Not Available]. PMID- 20291613 TI - [Not Available]. PMID- 20291612 TI - [Not Available]. PMID- 20291614 TI - [Not Available]. PMID- 20291615 TI - [Not Available]. PMID- 20291616 TI - [Not Available]. PMID- 20291617 TI - [Not Available]. PMID- 20291618 TI - [Not Available]. PMID- 20291619 TI - [Not Available]. PMID- 20291620 TI - [Not Available]. PMID- 20291621 TI - [Not Available]. PMID- 20291622 TI - [Not Available]. PMID- 20291623 TI - [Not Available]. PMID- 20291624 TI - [Not Available]. PMID- 20291625 TI - [Not Available]. PMID- 20291626 TI - [Not Available]. PMID- 20291627 TI - [Not Available]. PMID- 20291628 TI - [Not Available]. PMID- 20291629 TI - [Not Available]. PMID- 20291630 TI - [Not Available]. PMID- 20291631 TI - [Not Available]. PMID- 20291632 TI - [Not Available]. PMID- 20291634 TI - [Not Available]. PMID- 20291635 TI - [Not Available]. PMID- 20291633 TI - [Not Available]. PMID- 20291636 TI - [Not Available]. PMID- 20291637 TI - [Not Available]. PMID- 20291638 TI - [Not Available]. PMID- 20291639 TI - [Not Available]. PMID- 20291640 TI - [Not Available]. PMID- 20291641 TI - [Not Available]. PMID- 20291642 TI - [Not Available]. PMID- 20291644 TI - Carcinoma of the colon. PMID- 20291643 TI - [Not Available]. PMID- 20291645 TI - Carcinoma of the head of the pancreas. PMID- 20291646 TI - Anesthesia for prolonged operation. PMID- 20291647 TI - Extensive calcification of pancreas. PMID- 20291648 TI - Cause of congenital defects following rubella in mother; role of adrenals. PMID- 20291649 TI - A study of diets of patients in a prenatal clinic with an attempt to correlate dietary adequacy with physical findings. PMID- 20291650 TI - Pompholyx and its treatment. PMID- 20291651 TI - Studies of neuromuscular dysfunction; treatment of chronic multiple sclerosis with neostigmine and intensive muscle re-education. PMID- 20291652 TI - Thiouracil in the treatment of hyperthyroidism complicating pregnancy. PMID- 20291653 TI - The influence of adrenalectomy upon analgesic effectiveness of morphine in rats. PMID- 20291654 TI - Diaphragmatic hernia. PMID- 20291656 TI - Oral penicillin in pneumonia. PMID- 20291655 TI - Aminopyrine in the treatment of rheumatic fever. PMID- 20291657 TI - Parinaud's oculoglandular syndrome; report of a case of obscure etiology. PMID- 20291658 TI - Diagnosis and prognosis in cases of coarctation of the aorta. PMID- 20291659 TI - Coarctation of the aorta; experimental surgical aspects. PMID- 20291660 TI - Surgical treatment of coarctation of the aorta; report of case. PMID- 20291661 TI - The roentgenologic diagnosis of coarctation of the aorta. PMID- 20291662 TI - Coarctation of the aorta; surgical aspects. PMID- 20291663 TI - Pregnancy at term complicated by ruptured appendix. PMID- 20291664 TI - Complete duplication of the large intestine; report of case. PMID- 20291665 TI - The value of pulmonary function tests in thoracic surgery for pulmonary tuberculosis. PMID- 20291666 TI - Simplified equipment for estimating the diffusion of oxygen and carbon dioxide in the lungs. PMID- 20291667 TI - Gingival biopsy for the diagnosis of generalized amyloidosis; preliminary report. PMID- 20291668 TI - Thoracic surgery through the 15. century. PMID- 20291669 TI - Cavernostomy. PMID- 20291670 TI - Treatment of tuberculosis of the spine in children. PMID- 20291671 TI - [Not Available]. PMID- 20291672 TI - [Not Available]. PMID- 20291673 TI - [Not Available]. PMID- 20291674 TI - [Not Available]. PMID- 20291675 TI - [Not Available]. PMID- 20291676 TI - [Not Available]. PMID- 20291677 TI - [Not Available]. PMID- 20291678 TI - [Not Available]. PMID- 20291679 TI - [Not Available]. PMID- 20291680 TI - [Not Available]. PMID- 20291681 TI - [Not Available]. PMID- 20291682 TI - [Not Available]. PMID- 20291683 TI - [Not Available]. PMID- 20291684 TI - [Not Available]. PMID- 20291685 TI - [Not Available]. PMID- 20291686 TI - [Not Available]. PMID- 20291687 TI - [Not Available]. PMID- 20291688 TI - [Not Available]. PMID- 20291689 TI - [Not Available]. PMID- 20291690 TI - [Not Available]. PMID- 20291692 TI - Post-operative pulmonary complications. PMID- 20291691 TI - [Not Available]. PMID- 20291693 TI - Schistosomiasis in Southern Africa. PMID- 20291694 TI - Tallium-vergiftiging. PMID- 20291695 TI - Sensory disturbances in chronic visceral disease. PMID- 20291696 TI - Closed head injuries; a note on the indications for exploratory surgery. PMID- 20291697 TI - BERNARD Shaw and the late Dr. Kingston Barton. PMID- 20291698 TI - A case of a peptic ulcer. PMID- 20291699 TI - Indications for pulmonary resection. PMID- 20291700 TI - Management of the menopause and climacteric. PMID- 20291701 TI - The Rh factors in hemolytic disease of the newborn. PMID- 20291702 TI - The glaucoma patient. PMID- 20291703 TI - Clinical disorders associated with functional and organic disturbances in hypothalamic and other midbrain centers. PMID- 20291704 TI - Endocrine problems in childhood. PMID- 20291706 TI - An introduction to geriatrics. PMID- 20291705 TI - Hanging cast. PMID- 20291707 TI - The problems of the natural and artificial menopause. PMID- 20291708 TI - Cholecystitis. PMID- 20291709 TI - Significance of the liver in protein metabolism. PMID- 20291710 TI - Medical practice in China. PMID- 20291711 TI - Protein metabolism in relation to wounds, disease, infection and operative procedure. PMID- 20291712 TI - ANTIBIOTICS, clinical and laboratory studies. PMID- 20291713 TI - INJURIES of the central and peripheral nervous system. PMID- 20291714 TI - FROZEN-DRIED nerve grafts. PMID- 20291715 TI - ELECTRODIAGNOSIS of peripheral nerve lesions in man. PMID- 20291716 TI - Prevention of growth of hair in skin grafts. PMID- 20291718 TI - FURTHER studies on the antifilarial action and toxicity of cyanine dyes. PMID- 20291717 TI - Chemotherapy of tropical diseases, including amebiasis, leishmaniasis, schistosomiasis, and filariasis. PMID- 20291719 TI - SCREENING of compounds for activity against Schistosoma mansoni infestation in mice. PMID- 20291720 TI - Treatment of dermatophytosis and other fungous infections. PMID- 20291721 TI - SYPHILIS, false positive blood tests for. PMID- 20291722 TI - NITROGEN mustards, clinical trial of. PMID- 20291724 TI - MOSQUITO control investigations. PMID- 20291723 TI - INSECT repellents, insecticides and rodenticides, toxicity of. PMID- 20291725 TI - VIRULENCE and antigenicity of various strains of Vibrio cholerae. PMID- 20291726 TI - RICKETTSIAL diseases. PMID- 20291727 TI - VIRUS diseases. PMID- 20291729 TI - DYSENTERY, bacillary. PMID- 20291728 TI - SUBPROJECT on Japanese B encephalitis vaccine. PMID- 20291730 TI - Immunization against gas gangrene. PMID- 20291731 TI - Use of propylene glycol and other glycol vapors as means of air sterilization for control of air-borne infections. PMID- 20291732 TI - ABILITY of soldiers to work in humid heat. PMID- 20291733 TI - DEFICIENCY diseases. PMID- 20291734 TI - Caloric undernutrition in man. PMID- 20291735 TI - ARTIFICIAL limbs and hands. PMID- 20291736 TI - Wound ballistics. PMID- 20291737 TI - DENTAL caries. PMID- 20291738 TI - EQUINE influenza. PMID- 20291740 TI - Elementary particle physics. PMID- 20291739 TI - EQUINE encephalomyelitis. PMID- 20291741 TI - The mobilization of science for the war effort. PMID- 20291742 TI - Some aspects of mathematical research. PMID- 20291743 TI - India is like this. PMID- 20291744 TI - Research and industry. PMID- 20291745 TI - Report on the latest discoveries of early man in the Far East. PMID- 20291746 TI - [Not Available]. PMID- 20291747 TI - [Not Available]. PMID- 20291748 TI - [Not Available]. PMID- 20291749 TI - [Not Available]. PMID- 20291750 TI - [Not Available]. PMID- 20291751 TI - [Not Available]. PMID- 20291752 TI - [Not Available]. PMID- 20291753 TI - [Not Available]. PMID- 20291754 TI - [Not Available]. PMID- 20291755 TI - [Not Available]. PMID- 20291756 TI - [Not Available]. PMID- 20291757 TI - [Not Available]. PMID- 20291758 TI - [Not Available]. PMID- 20291759 TI - [Not Available]. PMID- 20291760 TI - [Not Available]. PMID- 20291761 TI - Substances thioloprives. PMID- 20291762 TI - [Not Available]. PMID- 20291763 TI - [Not Available]. PMID- 20291764 TI - The effect of sodium fluoride on the autoxidation of cysteine. PMID- 20291765 TI - [Not Available]. PMID- 20291766 TI - [Not Available]. PMID- 20291767 TI - Variations in Ca and Mg contents in Arbacia eggs as a result of fertilization. PMID- 20291768 TI - Sex-linkage in Culex molestus. PMID- 20291769 TI - X-ray analysis during the war years, 1946 conference. PMID- 20291771 TI - Substances thioloprives. PMID- 20291770 TI - Excitatory and inhibitory pathways involved in lower reflex integration. PMID- 20291772 TI - [Not Available]. PMID- 20291773 TI - [Not Available]. PMID- 20291774 TI - [Not Available]. PMID- 20291775 TI - [Not Available]. PMID- 20291776 TI - [Not Available]. PMID- 20291777 TI - Steroid thiazolidines, their possible biochemical significance. PMID- 20291778 TI - On the inactivation of thrombin. PMID- 20291779 TI - Enzyme preparations from cellulose-decomposing bacteria. PMID- 20291780 TI - [Not Available]. PMID- 20291781 TI - [Not Available]. PMID- 20291782 TI - The exploration of Antarctica. PMID- 20291783 TI - The mission of the universities. PMID- 20291784 TI - Astrology and astronomy in the seventeenth century. PMID- 20291786 TI - Permeability of insect cuticle. PMID- 20291785 TI - Phenolic substances concerned in hardening the insect cuticle. PMID- 20291787 TI - Spread around the initiating point of the detonation wave in high explosives. PMID- 20291788 TI - Lubricating properties of molecular layers of stearic acid and calcium stearate on metal surfaces. PMID- 20291789 TI - Activation of paludrine in vitro. PMID- 20291790 TI - Mauthner's cells in the larvae of anuran Amphibia. PMID- 20291791 TI - RELEASE of information on atomic energy. PMID- 20291792 TI - Atomic physics and international cooperation. PMID- 20291793 TI - An electronic reading aid for the blind. PMID- 20291794 TI - Techniques of race relations. PMID- 20291796 TI - Recent observations on programs for medicine and national health in the USSR. PMID- 20291795 TI - India's Pakistan issue. PMID- 20291798 TI - Measuring the effects of social case work. PMID- 20291797 TI - Some research in aids to the blind. PMID- 20291799 TI - The clinic team. PMID- 20291800 TI - Problems in clinical research. PMID- 20291801 TI - Age patterning in personality development. PMID- 20291802 TI - Developmental factors in relation to recidivism and non-recidivism among military delinquents. PMID- 20291803 TI - Group psychotherapy in an Army general hospital relating to civilian readjustment. PMID- 20291804 TI - The death of the leader in group psychotherapy. PMID- 20291805 TI - Studies in group symptom formation. PMID- 20291806 TI - Must individual and group psychotherapy be opposed? PMID- 20291807 TI - Differential dynamics of activity and interview group therapy. PMID- 20291808 TI - Group therapy in a child guidance center. PMID- 20291809 TI - Group therapy on a children's psychiatric ward, experiment combining group therapy with individual therapy and resident treatment. PMID- 20291810 TI - Fear of desertion by mother. PMID- 20291811 TI - A study of the thematic apparception tests of psychotic children. PMID- 20291813 TI - The problem of human difference and prejudice. PMID- 20291812 TI - The structure of dominance. PMID- 20291815 TI - Central course of afferent fibers for pain in facial glossopharyngeal and vagus nerves; clinical observations. PMID- 20291814 TI - Headache; the teeth as a source of headache and other pain. PMID- 20291816 TI - Meningeal reaction with abscess of the brain. PMID- 20291817 TI - Measurements of pain sensitivity in patients with psychoneurosis. PMID- 20291818 TI - Incidence of combat fatigue. PMID- 20291819 TI - Paramyoclonus multiplex (Friedreich); a clinicotherapeutic study. PMID- 20291820 TI - Retinal periphlebitis associated with paraplegia. PMID- 20291821 TI - Congenital facial paralysis. PMID- 20291822 TI - Cogwheel phenomenon of the eyes; its clinical significance. PMID- 20291823 TI - Localized nontraumatic neuropathy in military personnel. PMID- 20291825 TI - The Gerstmann syndrome; case report and review of the literature. PMID- 20291824 TI - The effect of oral administration of lactic acid upon the clinical course of depressive states. PMID- 20291826 TI - Conditioned PGR (psychogalvanic response) in states of pathological anxiety. PMID- 20291827 TI - Experience with insulin and electroshock treatment in an Army general hospital. PMID- 20291828 TI - Psychiatric ward management of the acute schizophrenic patient. PMID- 20291829 TI - An epidemic of encephalitis in the concentration camp Terezin (Theresienstadt) during the winter 1943-1944. PMID- 20291830 TI - Self-induced mediastinal emphysema in a psychotic; an attempt to commit suicide by means of the Valsalva experiment. PMID- 20291831 TI - Report on two cases of psychosis with Oedipus panic treated successfully with electric shock. PMID- 20291832 TI - Some results in mental and performance testing with neurologic patients. PMID- 20291833 TI - Effect of penicillin and other antibiotic substances on the central nervous system. PMID- 20291834 TI - Military neurology in India with especial reference to deficiency syndromes in ex prisoners of war. PMID- 20291835 TI - Decerebrate rigidity. PMID- 20291836 TI - Convulsive activity induced by fluoroacetate. PMID- 20291837 TI - Injury potentials along peripheral nerves in relation to histological structure. PMID- 20291838 TI - Injury potentials at different levels of cross-section of spinal cord. PMID- 20291839 TI - Effect of afferent impulses on cortical suppressor areas. PMID- 20291840 TI - Influence of suppressor areas on afferent impulses. PMID- 20291841 TI - Prolonged facilitation of synaptic excitation in sympathetic ganglia. PMID- 20291842 TI - Effect of di-isopropyl fluorphosphate (DFP) on action potential and cholinesterase of nerve. PMID- 20291843 TI - [Not Available]. PMID- 20291844 TI - [Not Available]. PMID- 20291845 TI - [Not Available]. PMID- 20291846 TI - [Not Available]. PMID- 20291847 TI - [Not Available]. PMID- 20291848 TI - [Not Available]. PMID- 20291849 TI - Camps as mental health institutions. PMID- 20291850 TI - Where the new camping tasks begin. PMID- 20291851 TI - The child's readiness for camp. PMID- 20291852 TI - Psychopathologic risks of camp life. PMID- 20291853 TI - Common emotional disturbances of children at camp. PMID- 20291854 TI - Camps for maladjusted children. PMID- 20291855 TI - The influence of the summer camp on personality development. PMID- 20291856 TI - The role of leadership in camping. PMID- 20291857 TI - Changes of attitudes subsequent to camp experience. PMID- 20291858 TI - An analysis of intra-camp relationships. PMID- 20291859 TI - The value of flexibility in a camp program. PMID- 20291860 TI - How much decentralized camping can do for the child. PMID- 20291861 TI - Some problems of therapeutic camping. PMID- 20291862 TI - Camp as a therapeutic community. PMID- 20291863 TI - The treatment potentialities of the summer camp for children with personality disturbances. PMID- 20291864 TI - On some neurotic difficulties in nursing mothers. PMID- 20291865 TI - Insight. PMID- 20291866 TI - Charon and the obolos. PMID- 20291867 TI - Audio-visual psychotherapeutics. PMID- 20291868 TI - A brief survey of the use of motion pictures for the treatment of neuropsychiatric patients. PMID- 20291869 TI - The art of state hospital nursing. PMID- 20291870 TI - Electric shock therapy. PMID- 20291871 TI - Comparison of the initial psychotic manifestations of veterans and civilians. PMID- 20291873 TI - Problems of suicide. PMID- 20291872 TI - Recreation work as a therapeutic adjunct on a neuropsychiatric service in an Army general hospital. PMID- 20291874 TI - Group techniques in the general hospital. PMID- 20291875 TI - POPULAR psychosurgery. PMID- 20291876 TI - The public health nurse and the emotions of pregnancy. PMID- 20291877 TI - The use of tests in professional nursing. PMID- 20291878 TI - Progress in merit system unit examinations. PMID- 20291879 TI - Chronic illness and the nurse. PMID- 20291880 TI - Medical-social aspects of cerebral palsy. PMID- 20291881 TI - Organizing the community for public health nursing. PMID- 20291882 TI - Keratoplasty as performed at Greens' Eye Hospital. PMID- 20291883 TI - Hemangloma of the choroid. PMID- 20291884 TI - Lempert fenestration; preliminary report of fifteen cases. PMID- 20291885 TI - Plastic surgery for outstanding ears; a simple surgical procedure. PMID- 20291886 TI - Subnormal accommodation. PMID- 20291887 TI - Stereoscopes for home use. PMID- 20291888 TI - Applied psychology in the treatment of the more serious ocular conditions. PMID- 20291889 TI - Ocular pain. PMID- 20291890 TI - Some important factors in strabismus surgery. PMID- 20291891 TI - An investigation of the properties of evaporated metal bolometers. PMID- 20291893 TI - Polarimetric methods for the determination of the refractive index and the thickness of thin films on glass. PMID- 20291892 TI - The measurement of the intensity ratios of spectral lines with electron multiplier photo-tubes. PMID- 20291894 TI - Spectrochemical analysis of high copper in cast iron and steel. PMID- 20291896 TI - Spectrochemical analysis of ceramics and other non-metallic materials. PMID- 20291895 TI - The spectrochemical analysis of nickel alloys. PMID- 20291897 TI - The relation of the configuration of a brightness contrast border to its visibility. PMID- 20291898 TI - A theoretical development of exact solution of reflectance of multiple layer optical coatings. PMID- 20291899 TI - Effect of a constant current on vision. PMID- 20291900 TI - Apparatus for determining spherical aberration of convex surface of paraboloid of revolution. PMID- 20291901 TI - A study concerning characteristics of the high-voltage a. c. arc. PMID- 20291902 TI - Optimum spectral sensitivities for a reversible color film process. PMID- 20291903 TI - A double-beam, percent transmission recording infra-red spectrophotometer. PMID- 20291904 TI - Gingival disease in relation to systemic disorders. PMID- 20291907 TI - Corrective surgery of the external nasal pyramid and the nasal septum for restoration of normal physiology. PMID- 20291906 TI - Bullet in right orbit; transantral extraction; case report. PMID- 20291905 TI - Further observations on the use of benadryl in hay fever, asthma, vasomotor rhinitis, and in mixed allergic groups. PMID- 20291908 TI - Rehabilitation of the hard of hearing. PMID- 20291909 TI - [Not Available]. PMID- 20291910 TI - [Not Available]. PMID- 20291911 TI - [Not Available]. PMID- 20291913 TI - [Not Available]. PMID- 20291912 TI - [Not Available]. PMID- 20291914 TI - [Not Available]. PMID- 20291915 TI - [Not Available]. PMID- 20291917 TI - [Not Available]. PMID- 20291916 TI - [Not Available]. PMID- 20291918 TI - [Not Available]. PMID- 20291919 TI - [Not Available]. PMID- 20291920 TI - [Not Available]. PMID- 20291921 TI - [Not Available]. PMID- 20291922 TI - [Not Available]. PMID- 20291923 TI - [Not Available]. PMID- 20291924 TI - [Not Available]. PMID- 20291925 TI - Jaundice and abdominal enlargement. [incomplete transposition of the viscera]. PMID- 20291926 TI - Diarrhea; heavy breathing; cough. [urethra stricture]. PMID- 20291927 TI - Rash on the skin. [pyoderma; acute pericarditis]. PMID- 20291928 TI - Listlessness; coma [pyelonephritis]. PMID- 20291929 TI - Care of the aged and chronically ill. PMID- 20291930 TI - Chemical microscopy of essential oils; cassia and cinnamon oils. PMID- 20291931 TI - How to undermine your health. PMID- 20291932 TI - Ancient Greek versus modern medicine. PMID- 20291933 TI - Newer hemostatics. PMID- 20291934 TI - Particles in ampules. PMID- 20291935 TI - A three-hour physical development cup-plate assay for penicillin. PMID- 20291936 TI - Influence of phosphate on stability of partially purified penicillins. PMID- 20291937 TI - On the oxytocic activity of pitocin and pitressin on isolated segments of mammalian uteri by a graded response method. PMID- 20291938 TI - Synthesis of iodosulfophenylazo and iodocarboxyphenylazo derivatives of 1-amino-8 naphthol-2,4-disulfonic acid. PMID- 20291939 TI - The in vitro antibacterial action of dialkyl-aminoalkyl ethers of stilbestrol and hexylresorcinol. PMID- 20291940 TI - On the stability of vitamin C in aqueous solutions and in pharmaceutical preparations. PMID- 20291941 TI - Pharmacognostical studies of four American arnieas. PMID- 20291942 TI - Pyrogen testing with Polish rabbits. PMID- 20291943 TI - Lipid metabolism and development of anemia in splenectomized guinea pigs fed cholesterol. PMID- 20291944 TI - The response of the triceps surae of normal, adrenalectomized, desoxycorticosterone acetate-treated and KCl-treated rats to direct and indirect, single and repetitive stimulation. PMID- 20291945 TI - Modification of respiratory movements by vagal stimulation. PMID- 20291946 TI - The respiratory and circulatory response of normal man to inhalation of 7.6 and 10.4 per cent CO2 with a comparison of the maximal ventilation produced by severe muscular exercise, inhalation of CO2 and maximal voluntary hyperventilation. PMID- 20291947 TI - Disturbances in the chemistry and in the acid-base balance of the blood of dogs in hemorrhagic and traumatic shock. PMID- 20291948 TI - The effect of intravenous adrenalin on blood flow, sugar retention, lactate output and respiratory metabolism of peripheral (leg) tissues in the anesthetized cat. PMID- 20291949 TI - Factors affecting the electrical potential of the gastric mucosa. PMID- 20291950 TI - The interaction of prothrombin A and B. PMID- 20291951 TI - The effect of insulin on food intake after vagotomy and sympathectomy. PMID- 20291952 TI - The effect of various degrees of anoxic anoxia on water distribution in the body. PMID- 20291953 TI - The influence of test meal composition on gastric emptying in man. PMID- 20291954 TI - Evidence, from crosstransfusion experiments, that no toxic factor is present in ischemic compression shock capable of inducing a shock state in normal dogs. PMID- 20291955 TI - The active principle of placental toxin; thromboplastin; its inactivator in blood; antithromboplastin. PMID- 20291956 TI - The renal clearance of essential amino acids; arginine histidine, lysine and methionine. PMID- 20291957 TI - Audiogenic fits produced by magnesium deficiency in tame domestic Norway rats and in wild Norway and Alexandrine rats. PMID- 20291958 TI - Further observations on factors influencing the biochemical appraisal of nutritional status. PMID- 20291959 TI - Studies on frost-bite with special reference to treatment and the effect on minute blood vessels. PMID- 20291960 TI - The effect of pilocarpine, mecholyl, atropine and alcohol on the gastric potential and the secretion of hydrochloric acid. PMID- 20291961 TI - The effect of muscular fatigue on the solubility of myosin. PMID- 20291962 TI - The effect of heavy muscular work on the volume of circulating red corpuscles in man. PMID- 20291963 TI - The effect of experimental insomnia on the rate of potential changes in the brain. PMID- 20291964 TI - Physical capacity of rats in relation to energy and fat content of the diet. PMID- 20291965 TI - Thermal responses and efficiency of sweating when men are dressed in Arctic clothing and exposed to extreme cold. PMID- 20291966 TI - Analysis of factors concerned in maintaining energy balance for dressed men in extreme cold; effects of activity on the protective value and comfort of an Arctic uniform. PMID- 20291967 TI - The relationship between traumatic shock and the release of adenylic acid compounds. PMID- 20291968 TI - Effect of frontal lobectomy on blood sugars of normal cats and monkeys and adrenal denervated cats. PMID- 20291969 TI - The relation of load test response and fasting excretion levels to tissue content of thiamine and riboflavin. PMID- 20291970 TI - Electrocardiographic changes induced by cooling or warming the inner surface of the dog's ventricle. PMID- 20291971 TI - [Not Available]. PMID- 20291972 TI - [Not Available]. PMID- 20291973 TI - [Not Available]. PMID- 20291974 TI - [Not Available]. PMID- 20291975 TI - [Not Available]. PMID- 20291976 TI - [Not Available]. PMID- 20291978 TI - [Not Available]. PMID- 20291977 TI - [Not Available]. PMID- 20291979 TI - [Not Available]. PMID- 20291980 TI - [Not Available]. PMID- 20291981 TI - [Not Available]. PMID- 20291982 TI - [Not Available]. PMID- 20291983 TI - [Not Available]. PMID- 20291984 TI - [Not Available]. PMID- 20291985 TI - [Not Available]. PMID- 20291986 TI - [Not Available]. PMID- 20291988 TI - [Not Available]. PMID- 20291987 TI - [Not Available]. PMID- 20291989 TI - [Not Available]. PMID- 20291990 TI - [Not Available]. PMID- 20291991 TI - [Not Available]. PMID- 20291993 TI - [Not Available]. PMID- 20291992 TI - [Not Available]. PMID- 20291994 TI - [Not Available]. PMID- 20291995 TI - [Not Available]. PMID- 20291996 TI - [Not Available]. PMID- 20291997 TI - [Not Available]. PMID- 20291998 TI - [Not Available]. PMID- 20291999 TI - [Not Available]. PMID- 20292001 TI - [Not Available]. PMID- 20292000 TI - [Not Available]. PMID- 20292002 TI - [Not Available]. PMID- 20292003 TI - [Not Available]. PMID- 20292004 TI - [Not Available]. PMID- 20292005 TI - [Not Available]. PMID- 20292006 TI - [Not Available]. PMID- 20292007 TI - [Not Available]. PMID- 20292008 TI - [Not Available]. PMID- 20292009 TI - [Not Available]. PMID- 20292010 TI - [Not Available]. PMID- 20292011 TI - [Not Available]. PMID- 20292012 TI - [Not Available]. PMID- 20292013 TI - [Not Available]. PMID- 20292014 TI - [Not Available]. PMID- 20292015 TI - [Not Available]. PMID- 20292016 TI - Job attitudes of life insurance agents. PMID- 20292017 TI - The psychological barometer of public attitudes. PMID- 20292018 TI - Some comments on the Army general classification test. PMID- 20292019 TI - The MacQuarrie test for mechanical ability; factor analysis. PMID- 20292020 TI - Reliability of the Grove modification of the Kent-Shakow formboard series. PMID- 20292021 TI - Influence of leading upon readability of newspaper type. PMID- 20292022 TI - Prediction of success in learning Japanese. PMID- 20292023 TI - Effect of a guidance program on emotional development. PMID- 20292024 TI - Further application of simplified scoring of the Bernreuter personality inventory. PMID- 20292025 TI - Braille edition of the Minnesota multiphasic personality inventory for use with the blind. PMID- 20292026 TI - Studies in projective techniques; the reliability of a multiple choice group Rorschach test. PMID- 20292027 TI - A note on the Hankes test scoring machine. PMID- 20292028 TI - The importance of clinical psychology in a complete medical program. PMID- 20292029 TI - Rorschach findings on college students showing different constellations of subscores on the A. C. E. PMID- 20292030 TI - A Rorschach study of a group of scientists and technicians. PMID- 20292032 TI - Ten years of journalism in psychology, 1937-1946. PMID- 20292031 TI - Origin of impractical or unrealistic vocational goals. PMID- 20292033 TI - Some lessons of wartime psychiatry. PMID- 20292034 TI - Control of Anopheles pseudopunctipennis in Mexico with DDT residual sprays applied in buildings. PMID- 20292035 TI - The effectiveness of DDT residual house sprays in controlling Anopheles quadrimaculatus. PMID- 20292036 TI - The antigenic composition and the effect of various extracts of Trypanosoma equiperdum and Trypanosoma lewisi on the leucocyte picture in experimental trypanosomiasis. PMID- 20292037 TI - The diagnosis of schistosomiasis japonica by means of intradermal and serological tests. PMID- 20292038 TI - The epidemiology of Schistosomiasis japonica in the Philippine Islands and Japan; surveys for schistosomiasis japonica on Mindanao, Philippine Islands. PMID- 20292039 TI - Effect of insulin on Plasmodium lophurae infection in ducks. PMID- 20292040 TI - Fomiteborne ancylostomiasis. PMID- 20292041 TI - The occurrence of Trombicula deliensis Walch in southwestern China. PMID- 20292042 TI - Poliomyelitis in Japan. PMID- 20292043 TI - Isolation of poliomyelitis virus from the throats of symptomless children. PMID- 20292044 TI - Attempts to infect African green monkeys by oral administration of poliomyelitis virus. PMID- 20292045 TI - The rise and decline of poliomyelitis virus levels in infected nervous tissue. PMID- 20292046 TI - Poliomyelitis virus in urban sewage in epidemic and in nonepidemic times. PMID- 20292047 TI - Effectiveness of various rodenticides on populations of brown rats in Baltimore. Maryland. PMID- 20292048 TI - Dust and its control as a means of disinfection of air. PMID- 20292049 TI - Problems and errors in assigning causes of bacterial food poisoning. PMID- 20292050 TI - Inactivation of the virus of infectious hepatitis in drinking water. PMID- 20292051 TI - Investigations of the swab rinse technic for examining eating and drinking utensils. PMID- 20292052 TI - Critical study of machine dishwashing. PMID- 20292053 TI - Field studies relating to immunity in infectious hepatitis and homologous serum jaundice. PMID- 20292054 TI - A review of induction and discharge examinations for tuberculosis in the Army. PMID- 20292055 TI - Demonstration of hormesis (increase in fatality rate) by penicillin. PMID- 20292056 TI - Public opinion measurement as an instrument in public health practice. PMID- 20292057 TI - Report of an outbreak of Q fever at the National Institute of Health. PMID- 20292058 TI - Studies on histoplasmosis in a rural community. PMID- 20292059 TI - School health today and tomorrow. PMID- 20292060 TI - [Not Available]. PMID- 20292061 TI - [Not Available]. PMID- 20292062 TI - [Not Available]. PMID- 20292063 TI - [Not Available]. PMID- 20292064 TI - [Not Available]. PMID- 20292065 TI - [Not Available]. PMID- 20292066 TI - [Not Available]. PMID- 20292067 TI - Some observations on the prevalence of rheumatic heart disease in Canada. PMID- 20292068 TI - The clinical study of neurotic disorders in the plant. PMID- 20292069 TI - Plague, Rocky Mountain spotted fever, and tularaemia surveys in Canada. PMID- 20292070 TI - A study of the diphtheria antitoxin response to recall doses of specific antigen. PMID- 20292071 TI - The standardization of influenza vaccine by red cell agglutination and antigenic tests in mice. PMID- 20292072 TI - The British citizen and his nurse. PMID- 20292073 TI - Northamptonshire; mass miniature radiography 1945-1946; occupational incidence of acute phthisis as shown by first survey of industrial centres in county. PMID- 20292075 TI - An hypothesis to account for certain intractable cases of atopic eczema. PMID- 20292074 TI - The early medical problems of displaced persons camps in Austria. PMID- 20292076 TI - Fatal anaphylactic shock due to a bee sting in the finger. PMID- 20292077 TI - Granuloma inguinale; a report of two cases. PMID- 20292078 TI - Periureteral sclerosing granuloma. PMID- 20292079 TI - Fatal human salmonellosis due to Salmonella senftenberg. PMID- 20292080 TI - Clinical and laboratory findings in eighty-six sporadic cases of salmonellosis. PMID- 20292081 TI - The current threat to animal experimentation. PMID- 20292082 TI - Functions of a blood bank. PMID- 20292083 TI - The Rh factor; its clinical significance; the organization of a blood grouping laboratory. PMID- 20292084 TI - Lymphogranuloma venereum; clinical and laboratory aspects, epidemiology, and treatment. PMID- 20292085 TI - Chancroid; granuloma inguinale; clinical and laboratory aspects epidemiology, and treatment. PMID- 20292086 TI - The measurement of sports ability in high school girls. PMID- 20292087 TI - The JCR test. PMID- 20292088 TI - Development of motor coordination in boys and girls. PMID- 20292089 TI - Use of the Billig exercise for dysmenorrhea for college women. PMID- 20292090 TI - An analysis of the prewar certification requirements for teachers of health and physical education in the forty-eight states. PMID- 20292091 TI - The organization of a veterans' physical education program. PMID- 20292092 TI - A study of the physical inspection programs for girls in colleges and universities of the Midwest District. PMID- 20292093 TI - LOUISIANA summary of vital statistics, 1944. PMID- 20292094 TI - MAINE summary of vital statistics, 1944. PMID- 20292095 TI - MARYLAND summary of vital statistics, 1944. PMID- 20292096 TI - MASSACHUSETTS summary of vital statistics, 1944. PMID- 20292097 TI - Compound injuries of the knee joint; the infected knee joint. PMID- 20292103 TI - Bacteriologic study of burn wounds. PMID- 20292104 TI - Bacteriologic study of burn wounds; the development of resistance to penicillin by the flora of full-thickness burn wounds in patients treated with penicillin systemically. PMID- 20292105 TI - Bacteriologic study of burn wounds; the incidence, virulence and resistance to penicillin of the staphylococcus in burn wounds of patients treated with penicillin or sulfonamides; the significance of staphylococcal immunity to the healing of the wounds infected with the staphylococcus. PMID- 20292106 TI - Bacteriologic study of burn wounds; the incidence, virulence and resistance to penicillin of the streptococcus in burn wounds of patients treated with penicillin or sulfonamides. PMID- 20292107 TI - Experiences with sympathectomy for sequelae of trench feet. PMID- 20292108 TI - Ligature carrier for vaginal hysterectomy. PMID- 20292109 TI - Solitary eosinophilic granuloma of rib. PMID- 20292110 TI - [Not Available]. PMID- 20292111 TI - [Not Available]. PMID- 20292112 TI - [Not Available]. PMID- 20292113 TI - [Not Available]. PMID- 20292114 TI - [Not Available]. PMID- 20292115 TI - [Not Available]. PMID- 20292116 TI - [Not Available]. PMID- 20292117 TI - [Not Available]. PMID- 20292118 TI - [Not Available]. PMID- 20292119 TI - [Not Available]. PMID- 20292120 TI - [Not Available]. PMID- 20292121 TI - [Not Available]. PMID- 20292122 TI - [Not Available]. PMID- 20292123 TI - [Not Available]. PMID- 20292124 TI - [Not Available]. PMID- 20292125 TI - [Not Available]. PMID- 20292127 TI - [Not Available]. PMID- 20292126 TI - [Not Available]. PMID- 20292128 TI - [Not Available]. PMID- 20292129 TI - Pilonidal cyst; report of 17 consecutive cases treated by marsupialization. PMID- 20292131 TI - Interinnomino-abdominal amputation of the lower extremity with indications for the extension of its use. PMID- 20292130 TI - Behavior in serum of various metals used in bone surgery. PMID- 20292132 TI - Skeletal traction for fractures of the hand. PMID- 20292133 TI - The spread of carcinoma of the stomach. PMID- 20292134 TI - Spontaneous rupture of the uterus. PMID- 20292135 TI - Coccygodynia; review of the literature and presentation of cases. PMID- 20292136 TI - War experiences in the treatment of spinal cord injuries. PMID- 20292137 TI - PROCEEDINGS of the 32. Annual Clinical Congress of the American College of Surgeons. PMID- 20292139 TI - The American surgeon, A.U.S. PMID- 20292138 TI - Interruption of the deep veins of the lower extremities in the prevention and treatment of thrombosis and embolism. PMID- 20292140 TI - Penicillin; its use in surgery and influence on earlier types of chemotherapy. PMID- 20292142 TI - Modern methods in the treatment of fractures. PMID- 20292141 TI - Cancellous bone grafts to the jaw. PMID- 20292143 TI - The surgeon and his trust; with special reference to safe conduct of the patient through operation. PMID- 20292144 TI - Clinical uses of streptomycin in medicine and surgery. PMID- 20292145 TI - Thiouracil and iodine; the preoperative management of the thyrotoxic patient. PMID- 20292146 TI - Fluid and electrolyte balance. PMID- 20292147 TI - Use of blood and blood substitutes. PMID- 20292148 TI - Ligation of the inferior vena cava in thrombosis of the deep veins of the lower extremities. PMID- 20292149 TI - Nutritional preparation for substandard risk patients. PMID- 20292150 TI - Complete occlusion of the abdominal aorta; report of two patients diagnosed by aortography. PMID- 20292151 TI - Experimental aortic valvulotomy; a preliminary report. PMID- 20292152 TI - Arteriovenous fistula; experimental study of influence of sympathetic nervous system on development of collateral circulation. PMID- 20292153 TI - A new operative treatment for elephantiasis. PMID- 20292154 TI - Indications for portacaval anastomosis; analysis of cases. PMID- 20292155 TI - Anomalies of the pulmonary veins; their surgical significance. PMID- 20292156 TI - The use of vasodilatation in the treatment of venous thrombosis. PMID- 20292157 TI - Anticoagulants in venous thrombosis and the prevention of pulmonary embolism. PMID- 20292158 TI - Carcinoma of the colon; a statistical analysis. PMID- 20292159 TI - Anticoagulant therapy in thrombosis. PMID- 20292160 TI - The treatment of chronic nontuberculous pulmonary abscesses by high vacuum suction drainage. PMID- 20292161 TI - Rate of gain in strength in sutured abdominal wall wounds. PMID- 20292162 TI - Experiments with nonirritating glove powder. PMID- 20292163 TI - Experimental implantation of the common bile duct into the intestine. PMID- 20292164 TI - Principles involved in surgical therapy of encapsulated fibrosarcoma of soft tissues. PMID- 20292165 TI - Pancreatic reflux deliberately produced. PMID- 20292166 TI - The effect of early postoperative rising on the recurrence rate of hernia. PMID- 20292167 TI - The use of the male sex hormone in women with breast cancer. PMID- 20292168 TI - Resection of intra-abdominal cancer that has invaded the anterior abdominal wall. PMID- 20292169 TI - Observations on the genetic nature of gastric cancer in mice. PMID- 20292170 TI - Correlation of the use of antibiotic and chemotherapeutic agents with general principles of surgery. PMID- 20292171 TI - Physiologic aspects of surgical infections. PMID- 20292172 TI - Sympathetic interruption in cases of trauma and in posttraumatic states. PMID- 20292173 TI - The transportation of soldiers with fractures. PMID- 20292175 TI - Major amputations. PMID- 20292174 TI - Penicillin in experimental intestinal obstruction; a summary of observations with reference to their clinical application. PMID- 20292176 TI - Advances in bone graft surgery attributed to World War II. PMID- 20292177 TI - Fracture of the carpal scaphoid. PMID- 20292178 TI - Management of compound fractures in their early phases. PMID- 20292179 TI - Osteomyelitis following compound fractures. PMID- 20292180 TI - Applied anatomy in eye surgery. PMID- 20292181 TI - The management of strabismus in children. PMID- 20292182 TI - A new type of basket implant for use after enucleation. PMID- 20292183 TI - Reconstruction of orbital floor defects. PMID- 20292184 TI - The reconstruction of the upper lid. PMID- 20292185 TI - The management of nonmagnetic intraocular foreign bodies. PMID- 20292187 TI - The fenestration operation; an evaluation of its present status. PMID- 20292186 TI - Visual field defects due to head injuries. PMID- 20292188 TI - The use of radium in the treatment of conductive deafness. PMID- 20292189 TI - Consideration of hearing impairment in the treatment of chronic suppurative otitis media. PMID- 20292190 TI - Indications for surgery in the light of the use of antibiotics. PMID- 20292191 TI - External sinus surgery. PMID- 20292193 TI - The closure of surface defects with free skin grafts and with pedicle flaps. PMID- 20292192 TI - Intranasal surgery. PMID- 20292194 TI - Neutralization of color in capillary hemangiomas of the face by intradermal injection (tattooing) of permanent pigments. PMID- 20292196 TI - Studies in the anatomy and repair of cleft palate. PMID- 20292195 TI - Preservation of jaw function following surgery and trauma. PMID- 20292197 TI - Graduate training in surgery. PMID- 20292198 TI - Preservation of the upper pelvic floor and bladder support in total hysterectomy. PMID- 20292199 TI - A report on experience with vaginal hysterectomy. PMID- 20292200 TI - The present status of prostatic resection. PMID- 20292201 TI - The Rh factor; its present status and clinical importance. PMID- 20292202 TI - Recent advances in neurosurgery. PMID- 20292203 TI - Chronic lymphatic leukemia. PMID- 20292204 TI - Surgery since the birth of the North Pacific Surgical Association. PMID- 20292205 TI - Psychiatric and physiologic studies on fatigue. PMID- 20292206 TI - The role of the physiologist in physical medicine. PMID- 20292208 TI - Foot strain; etiology and treatment. PMID- 20292207 TI - Reliability of a single effort muscle test. PMID- 20292209 TI - Physical medicine in the Army. PMID- 20292210 TI - Traumatic cerebral palsy. PMID- 20292211 TI - Physical therapy and chest surgery. PMID- 20292212 TI - Mental hygiene program for the cerebral palsied child. PMID- 20292213 TI - Physical therapy in a large general hospital. PMID- 20292214 TI - Physical therapy in a small general hospital. PMID- 20292215 TI - OPPORTUNITIES for advanced education for qualified physical therapists. PMID- 20292216 TI - Immunization of ducks against malaria by means of killed parasites with or without adjuvants. PMID- 20292217 TI - Premature rupture in schizogony; an explanation for multiple infection of red blood corpuscles with malaria parasites. PMID- 20292218 TI - Pacific vivax malaria in the American Negro. PMID- 20292219 TI - Fuadin therapy in 150 cases of schistosomiasis mansoni with a follow-up study of 70 cases. PMID- 20292220 TI - Parasitologic study of 400 soldiers interned by the Japanese. PMID- 20292221 TI - Agglutination of Endamoeba histolytica cysts. PMID- 20292222 TI - Preliminary report on field experiments to demonstrate effectiveness of various methods of malaria control. PMID- 20292223 TI - Radical cure of avian malaria (Plasmodium cathemerium) with SN 8557, a naphthoquinone derivative. PMID- 20292224 TI - Experimental chemotherapy of amebiasis. PMID- 20292225 TI - The reaction of woolly opossums (Caluromys laniger) to yellow fever virus. PMID- 20292226 TI - Reduction of anopheles density effected by the pre-season spraying of building interiors with DDT in kerosene, at Castel Volturno, Italy, in 1944-1945, and in the Tiber Delta in 1945. PMID- 20292227 TI - The periodicity of microfilariae in two patients with filariasis acquired in the South Pacific. PMID- 20292228 TI - Infectivity of Pacific island Wuchereria bancrofti to mosquitoes of the United States. PMID- 20292229 TI - Use of dimethylphthalate impregnated clothing as protection against scrub typhus. PMID- 20292230 TI - Shigella carriers with special reference to their therapy, including the use of streptomycin. PMID- 20292231 TI - The cuticular morphology of some common microfilariae. PMID- 20292232 TI - Leishmaniasis in Greece. PMID- 20292233 TI - Exudate from millipedes with particular reference to its injurious effects. PMID- 20292234 TI - [Not Available]. PMID- 20292235 TI - [Not Available]. PMID- 20292236 TI - [Not Available]. PMID- 20292237 TI - [Not Available]. PMID- 20292238 TI - [Not Available]. PMID- 20292239 TI - [Not Available]. PMID- 20292240 TI - [Not Available]. PMID- 20292241 TI - [Not Available]. PMID- 20292242 TI - [Not Available]. PMID- 20292243 TI - [Not Available]. PMID- 20292244 TI - [Not Available]. PMID- 20292245 TI - [Not Available]. PMID- 20292246 TI - [Not Available]. PMID- 20292247 TI - [Not Available]. PMID- 20292248 TI - [Not Available]. PMID- 20292249 TI - [Not Available]. PMID- 20292250 TI - [Not Available]. PMID- 20292251 TI - [Not Available]. PMID- 20292252 TI - [Not Available]. PMID- 20292253 TI - [Not Available]. PMID- 20292254 TI - [Not Available]. PMID- 20292255 TI - [Not Available]. PMID- 20292256 TI - [Not Available]. PMID- 20292257 TI - [Not Available]. PMID- 20292259 TI - [Not Available]. PMID- 20292258 TI - [Not Available]. PMID- 20292260 TI - [Not Available]. PMID- 20292261 TI - [Not Available]. PMID- 20292262 TI - [Not Available]. PMID- 20292263 TI - [Not Available]. PMID- 20292264 TI - [Not Available]. PMID- 20292265 TI - [Not Available]. PMID- 20292266 TI - [Not Available]. PMID- 20292267 TI - [Not Available]. PMID- 20292268 TI - [Not Available]. PMID- 20292269 TI - [Not Available]. PMID- 20292270 TI - [Not Available]. PMID- 20292271 TI - [Not Available]. PMID- 20292272 TI - [Not Available]. PMID- 20292273 TI - [Not Available]. PMID- 20292274 TI - [Not Available]. PMID- 20292275 TI - The relation between renal tuberculosis and primary infection. PMID- 20292276 TI - Adhesion formation after pneumoperitoneum. PMID- 20292277 TI - The prognosis of primary tuberculosis of the lung. PMID- 20292278 TI - A case of sarcoidosis of the lung with regional ileitis. PMID- 20292279 TI - Observations on some metabolic disorders of cows as evidenced by chemical analysis of samples of blood from clinical cases; some aspects of blood chemistry. PMID- 20292280 TI - Joint-ill in foals (pyosepticaemia); with special reference to the prophylactic treatment of the foal at birth. PMID- 20292281 TI - An interesting sarcoma in the thorax of a pig. PMID- 20292282 TI - The isolation of S. typhimurium from fowls which gave a positive agglutination test with S. pullorum antigen. PMID- 20292283 TI - Joint-ill in foals (pyosepticaemia); with special reference to the prophylactic treatment of the foal at birth. PMID- 20292284 TI - COMPARISON between the double intradermal comparative test and the single intradermal comparative test. PMID- 20292285 TI - Gestation periods; a coincidence. PMID- 20292286 TI - Congenital goitre in lambs. PMID- 20292287 TI - Diagnosis of traumatic reticulitis and pericarditis of bovines. PMID- 20292288 TI - Sympathectomy as an antiallergic measure. PMID- 20292289 TI - Allergic reactions from handling penicillin. PMID- 20292290 TI - The use of benadryl in the treatment of certain allergic diseases of children. PMID- 20292291 TI - Antihistaminic substances and experimental sensitizations. PMID- 20292292 TI - Does the routine treatment of asthma need revision? PMID- 20292293 TI - Eczematoid monilid of the eyelids (candidid). PMID- 20292294 TI - Timothy versus Bermuda grass. PMID- 20292295 TI - The chemical and immunologic basis of oral pollen propeptan therapy in hay fever. PMID- 20292296 TI - Use of crotalin in the prevention of anaphylactic shock in guinea pigs. PMID- 20292297 TI - Miscellaneous allergy; a critical review of recent literature. PMID- 20292298 TI - Sex difference in the size of the lymph nodes and spleen in guinea-pigs. PMID- 20292299 TI - [Not Available]. PMID- 20292300 TI - [Not Available]. PMID- 20292301 TI - [Not Available]. PMID- 20292302 TI - The microscopical structure of an experimentally produced phocomelias in the amphibian embryo. PMID- 20292303 TI - [Not Available]. PMID- 20292304 TI - [Not Available]. PMID- 20292305 TI - [Not Available]. PMID- 20292307 TI - [Not Available]. PMID- 20292306 TI - The role played by the axon and the Schwann cells in the degree of myelination of the peripheral nerve fibre. PMID- 20292308 TI - [Not Available]. PMID- 20292309 TI - [Not Available]. PMID- 20292310 TI - [Not Available]. PMID- 20292311 TI - The influence of unilateral nephrectomy on the weight of the endocrine organs in mice. PMID- 20292312 TI - [Not Available]. PMID- 20292313 TI - On the enlarging effect of desoxicorticosterone acetate on the kidneys of female mice. PMID- 20292314 TI - Maturation of regenerating nerve fibres with various peripheral connexions. PMID- 20292316 TI - The development of joints. PMID- 20292315 TI - Sensory fibres in the hypoglossal nerve. PMID- 20292317 TI - The growth and maturation of regenerating striated muscle fibres. PMID- 20292318 TI - The prenatal medullation of the sheep's nervous system. PMID- 20292319 TI - Cyclical changes in the islets of Langerhans, in the rat pancreas. PMID- 20292320 TI - The development of the specialized conducting tissue of the human heart. PMID- 20292321 TI - The radiographic demonstration of the mode of action of the heart of the frog. PMID- 20292322 TI - Respiratory displacement of larynx, hyoid bone and tongue. PMID- 20292323 TI - Civilian and military aspects of intravenous anesthesia. PMID- 20292324 TI - The general pharmacologic action of a new vasopressor drug, EA-83 (2-methylamino 6-hydroxy-6-methyl heptane, 2-methylamino iso-octanol). PMID- 20292325 TI - The analeptic effect of sodium succinate on barbiturate depression in man. PMID- 20292326 TI - Monocaine hydrochloride for nerve block procedures. PMID- 20292328 TI - PSYCHOLOGICAL impact of aircraft accidents. PMID- 20292327 TI - Acute acetone poisoning (resulting from synthetic plaster substitute in spica cast). PMID- 20292329 TI - Comparative bacteriostatic assays with rosaniline and its phenolic analog (rosolic acid). PMID- 20292334 TI - The nutrition of Protozoa; a simplified medium for the investigation of unknown factors in blood serum essential for the sustained growth of Trichomonas vaginalis. PMID- 20292335 TI - The nutrition of Protozoa; the separation of human blood serum into two fractions, both essential for the sustained growth of Trichomonas vaginalis. PMID- 20292336 TI - Studies on the morphology of the elementary bodies of fowl pox. PMID- 20292340 TI - A rapid method for the staining of Rickettsia orientalis. PMID- 20292341 TI - Observations on the in vivo and in vitro development of bacterial resistance to streptomycin. PMID- 20292342 TI - Studies on hemolytic streptococci; differentiation of species in streptococci of group A. PMID- 20292343 TI - A typhoid like infection with Salmonella gatuni. PMID- 20292346 TI - Quantitative measurement of growth of Mycobacterium tuberculosis; effect of streptomycin. PMID- 20292347 TI - Studies on the dehydrogenases of Clostridium perfringens. PMID- 20292348 TI - Bacteriologic studies in epilepsy and schizophrenia. PMID- 20292349 TI - The significance of, and methods for, maintaining moisture in bacteriological culture media. PMID- 20292350 TI - The utilization of thin paper discs in the assay of amylases. PMID- 20292351 TI - The saturation of bacterial lipids as a function of temperature. PMID- 20292352 TI - Penicillin and sulfadiazine sensitivity of 385 strains of Corynebacterium diphtheriae. PMID- 20292353 TI - Studies in the comparative anatomy and systematic importance of the hexapod tentorium; Dermaptera, Embioptera and Isoptera. PMID- 20292354 TI - The rate of CO2 production by cockroaches dusted with DDT and other insecticidal dusts. PMID- 20292355 TI - Chemoprophylaxis in the prevention of disease with especial reference to meningococcal infections; a comparative study of the absorption persistence and excretion of four sulfonamide compounds. PMID- 20292356 TI - Growth curves of nations. PMID- 20292357 TI - A study of fetal movements in relation to mother's activity. PMID- 20292358 TI - Probability of death and expectation of life. PMID- 20292359 TI - The nature of the action potentials of crustacean muscles. PMID- 20292360 TI - The formation and structure of the micropylar complex in the egg-shell of Rhodnius prolixus Stahl; (Heteroptera Reduviidae). PMID- 20292361 TI - The behaviour of wireworms in response to chemical stimulation. PMID- 20292362 TI - Spontaneous rhythmical impedance changes in the egg of the trout. PMID- 20292363 TI - An isolated nerve-muscle preparation from Ascaris lumbricoides. PMID- 20292364 TI - The responses of onion and lily mitosis to coumarin and parasorbic acid. PMID- 20292365 TI - The oxygen consumption of Gasterosteus aculeatus L. in toxic solutions. PMID- 20292366 TI - Studies on sterility and prenatal mortality in wild rabbits; the reliability of estimates of prenatal mortality based on counts of corpora lutea, implantation sites and embryos. PMID- 20292367 TI - Studies on sterility and prenatal mortality in wild rabbits; the occurrence of fibrin in the yolk-sac contents of embryos during and immediately after implantation. PMID- 20292368 TI - The production of fatty acids in the alimentary tract of the dog. PMID- 20292369 TI - Disk-sphere transformations produced by lysins, and their reversal, in systems of different pH. PMID- 20292370 TI - Studies in the development of the rainbow trout (Salmo irideus). PMID- 20292372 TI - The epicuticle in an insect, Rhodnius prolixus (Hemiptera). PMID- 20292371 TI - Transpiration and the structure of the epicuticle in ticks. PMID- 20292373 TI - A theory relating the action of salts on bacterial respiration to their influence on the solubility of proteins. PMID- 20292374 TI - The fine structure of the wall of the conifer tracheid; optical properties of dissected walls in Pinus insignis. PMID- 20292375 TI - Influence of steroid hormones on the sensitivity of adrenalectomized mice to procaine. PMID- 20292377 TI - Variation and structure of the eyes in the desert locust, Schistocerca gregaria (Forskal). PMID- 20292376 TI - The effects of selective breeding on the laboratory propagation of insect parasites. PMID- 20292378 TI - The effect of heat-denaturation on the base-finding capacity of beef-muscle press juice. PMID- 20292379 TI - Visual adaptation in relation to brief conditioning stimuli. PMID- 20292382 TI - The nature of fibrositis; multiple lesions and the neural hypothesis. PMID- 20292385 TI - Observations on the volume of the pulmonary circulation and its importance in the production of cyanosis and polycythemia. PMID- 20292386 TI - Studies on the coronary circulation; the collateral circulation of the normal human heart by coronary perfusion with radioactive erythrocytes and glass spheres. PMID- 20292387 TI - Incidence of thrombo-embolic lesions accompanying myocardial infarction. PMID- 20292388 TI - An experimental method for the closure of interauricular septal defects in dogs. PMID- 20292389 TI - Tolerance of the human heart to acidosis; reversible changes in RS-T interval during severe acidosis caused by administration of carbon dioxide. PMID- 20292390 TI - The influence of heart size on the circulation time. PMID- 20292391 TI - A preliminary study of the coronary circulation post mortem. PMID- 20292392 TI - Further observations on the treatment of the anginal syndrome with thiouracil. PMID- 20292393 TI - Raynaud's disease in men. PMID- 20292394 TI - Traumatic rupture of the aorta. PMID- 20292395 TI - Aneurysmal dilatation of the aorta associated with cystic medial necrosis. PMID- 20292396 TI - Wolff-Parkinson-White syndrome presenting certain unusual features. PMID- 20292397 TI - Pulmonary edema in the pregnant patient with mitral stenosis. PMID- 20292398 TI - Chronic fibroplastic myocarditis. PMID- 20292399 TI - Single coronary artery; case report of an absent right coronary artery. PMID- 20292400 TI - Ammi visnaga in the treatment of the anginal syndrome. PMID- 20292408 TI - Discussion on the treatment of bacterial endocarditis with penicillin. PMID- 20292409 TI - Bernheim's syndrome. PMID- 20292410 TI - Heart failure of unknown aetiology in Africans. PMID- 20292411 TI - Thoracolumbar sympathectomy and hypertension. PMID- 20292412 TI - Acute pericarditis in Still's disease. PMID- 20292413 TI - Recent advances in surgical treatment of patent ductus arteriosus. PMID- 20292414 TI - Some remarks on the statistical background in bio-assay. PMID- 20292415 TI - A new titrimetric method for the estimation of fluorine. PMID- 20292416 TI - The estimation of the volatile matter content of propellant explosives; the estimation of ethyl alcohol and ether. PMID- 20292417 TI - The determination of small amounts of aluminium by the aurintricarboxylate method. PMID- 20292418 TI - A colour reaction of certain classes of azo dyes with copper. PMID- 20292419 TI - The determination of copper in food. PMID- 20292420 TI - Furan and tetrahydrofuran derivatives; the synthesis and biological activity of a number of oxybiotin homologs. PMID- 20292421 TI - Purification of streptomycin salts by means of alumina. PMID- 20292422 TI - Rearrangement between primary ethanolamides of carboxylic acids and corresponding aminoethylesters. PMID- 20292423 TI - Preparation and properties of the iodohistidines. PMID- 20292424 TI - The ultraviolet absorption spectrum and the acid ionization constant of 8 hydroxyquinoline. PMID- 20292426 TI - Bacterial fractionation of oxygen isotopes. PMID- 20292425 TI - The heats of combustion of cyclopentane, cyclohexane, cycloheptane and cyclooctane. PMID- 20292427 TI - New syntheses of the selenium analogs of di-cystine and cysteine derivatives. PMID- 20292428 TI - A synthesis of selenium analogs of di-methionine and di-homocystine. PMID- 20292429 TI - Preparation and chromatographic separation of p-phenylazophenyl polyacetylglycosides. PMID- 20292430 TI - 5-Desoxy-L-sorbose. PMID- 20292431 TI - Hydrogenation of vitamin Bc (pteroylglutamic acid) and related pterines. PMID- 20292433 TI - The reaction between arsenicals and di-(p-biphenyl)-thiocarbazone. PMID- 20292432 TI - The reaction of certain secondary amines with phthalic anhydride; a new synthesis of beta-alanine. PMID- 20292434 TI - omega-Aurothio fatty acids and their salts. PMID- 20292435 TI - A blue-fluorescing compound, terthienyl, isolated from marigolds. PMID- 20292436 TI - The mechanism of urease inhibition by urea. PMID- 20292437 TI - A new synthesis of 1,2-benzanthracene. PMID- 20292438 TI - Studies on resin acids; carbinols. PMID- 20292439 TI - Oxidation-reduction potentials of thiol-dithio systems: thiourea-formamidine disulfide. PMID- 20292440 TI - Quinoline derivatives from 3-nitro-4-hydroxyquinoline. PMID- 20292441 TI - 8-Nitrocinchoninic acids and related substances. PMID- 20292442 TI - The mechanism of the anti-oxygenic synergism of quinones and quinols with phosphoric acid and other acids in fat systems. PMID- 20292443 TI - Preparation and properties of serum and plasma proteins; the conversion of human fibrinogen to fibrin under various conditions. PMID- 20292444 TI - Preparation and properties of serum and plasma proteins: human fibrin in the form of an elastic film. PMID- 20292445 TI - Preparation and properties of serum and plasma proteins; modification of the physical and chemical properties of fibrin film by heat treatment. PMID- 20292446 TI - Preparation and properties of serum and plasma proteins; quantitative interpretation of electrophoretic Schlieren diagrams of normal human plasma proteins. PMID- 20292447 TI - A photoelectric instrument for comparing the concentrations of very dilute aerosols, and measuring low light intensities. PMID- 20292448 TI - Absorption isotherm for determination of barium in quantities as low as 10-10 gram atom. PMID- 20292449 TI - The polarography of uranium; polarography in very weakly acid, neutral or basic solution. PMID- 20292450 TI - Esters of 2-furanacrylic acid. PMID- 20292451 TI - Tryptophan as a competitive growth inhibiting analog of phenylalanine. PMID- 20292452 TI - The reduction of 2-amino-4-methyl-5-beta-hydroxyethylthiazole in the synthesis of thiamin. PMID- 20292453 TI - Measurement of the cresolase activity of tyrosinase. PMID- 20292454 TI - The crystalline octaacetate of 6-alpha-d-glucopyranosido-beta-d-glucose. PMID- 20292455 TI - Actidione, an antibiotic from Streptomyces griseus. PMID- 20292456 TI - Thirteenth report of the Committee on Atomic Weights of the International Union of Chemistry. PMID- 20292457 TI - The diffusion coefficient of potassium chloride in dilute aqueous solution. PMID- 20292459 TI - Mechanism of decomposition of hydrogen peroxide solutions with manganese dioxide. PMID- 20292458 TI - Mechanism of decomposition of hydrogen peroxide solutions with manganese dioxide. PMID- 20292460 TI - Proton-deuteron exchange between ammonia and ammoniated diborane. PMID- 20292461 TI - The nature of the non-porphyrin bonding in derivatives of ferriheme. PMID- 20292462 TI - 1-Alkyl-1,2,3,4-tetrahydroquinoxalines. PMID- 20292463 TI - Absorption spectra and tautomerism of cyanuric acid, melamine and some related compounds. PMID- 20292464 TI - Organosilicon polymers; infrared spectra of the methylpolysiloxanes. PMID- 20292465 TI - Polarographic studies on extracted chlorophylls. PMID- 20292466 TI - The reactivity of hydrous alumina toward acids. PMID- 20292467 TI - Water absorption of proteins; the effect of free amino groups in casein. PMID- 20292468 TI - The oxidation of methyl linoleate at various temperatures. PMID- 20292469 TI - The ammonolysis of ethyl iodide by liquid ammonia. PMID- 20292470 TI - Activity of the red pigment from leguminous root nodules. PMID- 20292472 TI - Derivatives of piperazine; synthesis of piperazine and C-substituted piperazines. PMID- 20292471 TI - An improved synthesis of beta-alanine; the addition of ammonia to acrylonitrile at 50-150 degrees. PMID- 20292473 TI - The synthesis of 4-hydroxyquinolines; quinoline derivatives with sulfur containing substituents. PMID- 20292474 TI - delta-Tocopherol; isolation from soybean oil and properties. PMID- 20292475 TI - The heats of dilution of aqueous solutions of four amino butyric acids at 25 degrees. PMID- 20292476 TI - Sensitized catalysis; the fundamental facts. PMID- 20292477 TI - The controlled sodium amalgam reduction of aldonolactones and their esters to aldoses and an improved synthesis of d-arabinose. PMID- 20292478 TI - 1,5-Anhydro-xylitol. PMID- 20292479 TI - Derivatives of methylphenylarsine. PMID- 20292480 TI - Aliphatic chloroarsines. PMID- 20292481 TI - Nitroaryldichloroarsines and related compounds. PMID- 20292482 TI - Furan arsenicals. PMID- 20292483 TI - The reaction products of phenyldichloroarsine and acetylene. PMID- 20292484 TI - The anti-tubercular action of 1,1 1-trichloro-2,2-bis-(p-aminophenyl)-ethane. PMID- 20292485 TI - Ethyl formylaminomalonate; an intermediate in the synthesis of amino acids. PMID- 20292486 TI - The structure of adenosine triphosphate. PMID- 20292487 TI - Coumarins from 2-hydroxy-3-methoxybenzaldehyde. PMID- 20292488 TI - Relative stabilities of d-glucose-amine derivatives. PMID- 20292489 TI - Highly polymerized nucleic acid from yeast. PMID- 20292490 TI - The synthesis of cyclooctatetraene from pseudopelletierine. PMID- 20292491 TI - N,N-dimethyl-N'-(alpha-pyridyl)-N'-(alpha-theinyl)-methylenediamine, an antihistamic agent. PMID- 20292492 TI - The electric conductivity and the activation energy of ionic migration of molten salts and their mixtures. PMID- 20292493 TI - Non-specific catarrhal stomatitis. PMID- 20292494 TI - Orthodontia of yore. PMID- 20292495 TI - A simplified method of pain control. PMID- 20292496 TI - Restoration of upper anterior teeth with gold inlay and silicate. PMID- 20292497 TI - A rest splint for the relief of traumatic condylar intrusions. PMID- 20292498 TI - Odontoma: reports of two cases. PMID- 20292499 TI - Chronic enlargement of the maxilla and mandible. PMID- 20292500 TI - Observations on the possible significance of the exposed dental pulp as a portal of entry for the poliomyelitis virus. PMID- 20292501 TI - General practitioner must recognize need for space maintainers. PMID- 20292502 TI - Technic of apicoectomy requires only two sittings. PMID- 20292503 TI - Surgical preparation of the mouth for the reception of dentures. PMID- 20292504 TI - Uses of acrylic resins in dentistry. PMID- 20292506 TI - REQUIREMENTS for certification by the American Board of Oral Surgery. PMID- 20292505 TI - Root canal therapy. PMID- 20292507 TI - Dental education and the future of dentistry. PMID- 20292508 TI - Dissolution of tooth substance by lemon juice, acid beverages and acids from some other sources. PMID- 20292509 TI - Gold foil filling; description of special technic. PMID- 20292510 TI - Dental care for children in relation to geriatrics. PMID- 20292511 TI - A full gold crown, cast and readapted. PMID- 20292512 TI - Agglutination studies of the smaller oral treponemes, Borrelia vincenti and cultured strains of Treponema pallidum. PMID- 20292513 TI - Penicillin in the treatment of Vincent's infection. PMID- 20292514 TI - Dental caries. PMID- 20292515 TI - Auxiliary agencies in dental practice. PMID- 20292516 TI - Gold foil. PMID- 20292517 TI - The president's address to the Executive Council of the Federation Dentaire Internationale. PMID- 20292519 TI - [Not Available]. PMID- 20292518 TI - [Not Available]. PMID- 20292520 TI - Dentists face the law. PMID- 20292521 TI - The dangers of radical legislation. PMID- 20292522 TI - Radiodontic diagnosis of intra-oral neoplasms; benign neoplasms. PMID- 20292523 TI - Radiodontic diagnosis of intra-oral neoplasms; malignant neoplasms. PMID- 20292524 TI - Radiodontic diagnosis of intra-oral neoplasms; conditions that stimulate neoplasms. PMID- 20292525 TI - A study on reattachment of the supporting structures of the teeth. PMID- 20292526 TI - The preparation for certification in periodontology. PMID- 20292527 TI - Desensitizing dentin for cavity preparation. PMID- 20292529 TI - Case report; noma. PMID- 20292528 TI - Methods of payment as a factor in the dental care program. PMID- 20292530 TI - Hysteria conversion producing dental symptoms; case report. PMID- 20292531 TI - Dental caries control; a catechism. PMID- 20292532 TI - RESEARCH assistance; the United States Public Health Service. PMID- 20292533 TI - A basic approach to the problems of gingival disease. PMID- 20292534 TI - Simple method for securing centric jaw relationship. PMID- 20292535 TI - Lip retraction in the treatment of gingivitis. PMID- 20292536 TI - Penicillin in dental and oral surgery. PMID- 20292537 TI - Comparatively permanent silicate fillings. PMID- 20292538 TI - [Not Available]. PMID- 20292539 TI - [Not Available]. PMID- 20292540 TI - [Not Available]. PMID- 20292541 TI - [Not Available]. PMID- 20292542 TI - [Not Available]. PMID- 20292543 TI - [Not Available]. PMID- 20292544 TI - [Not Available]. PMID- 20292545 TI - [Not Available]. PMID- 20292546 TI - [Not Available]. PMID- 20292547 TI - [Not Available]. PMID- 20292548 TI - [Not Available]. PMID- 20292549 TI - [Not Available]. PMID- 20292550 TI - [Not Available]. PMID- 20292551 TI - [Not Available]. PMID- 20292552 TI - [Not Available]. PMID- 20292553 TI - [Not Available]. PMID- 20292554 TI - [Not Available]. PMID- 20292555 TI - [Not Available]. PMID- 20292556 TI - [Not Available]. PMID- 20292557 TI - [Not Available]. PMID- 20292558 TI - [Not Available]. PMID- 20292559 TI - [Not Available]. PMID- 20292560 TI - [Not Available]. PMID- 20292561 TI - [Not Available]. PMID- 20292562 TI - [Not Available]. PMID- 20292563 TI - [Not Available]. PMID- 20292564 TI - [Not Available]. PMID- 20292565 TI - [Not Available]. PMID- 20292566 TI - [Not Available]. PMID- 20292567 TI - [Not Available]. PMID- 20292568 TI - [Not Available]. PMID- 20292569 TI - [Not Available]. PMID- 20292570 TI - [Not Available]. PMID- 20292571 TI - [Not Available]. PMID- 20292572 TI - [Not Available]. PMID- 20292573 TI - [Not Available]. PMID- 20292575 TI - [Not Available]. PMID- 20292574 TI - [Not Available]. PMID- 20292576 TI - [Not Available]. PMID- 20292577 TI - [Not Available]. PMID- 20292578 TI - [Not Available]. PMID- 20292579 TI - [Not Available]. PMID- 20292580 TI - [Not Available]. PMID- 20292581 TI - [Not Available]. PMID- 20292582 TI - [Not Available]. PMID- 20292583 TI - [Not Available]. PMID- 20292584 TI - [Not Available]. PMID- 20292585 TI - [Not Available]. PMID- 20292586 TI - [Not Available]. PMID- 20292587 TI - [Not Available]. PMID- 20292588 TI - [Not Available]. PMID- 20292589 TI - [Not Available]. PMID- 20292590 TI - [Not Available]. PMID- 20292591 TI - [Not Available]. PMID- 20292592 TI - [Not Available]. PMID- 20292593 TI - [Not Available]. PMID- 20292594 TI - [Not Available]. PMID- 20292595 TI - [Not Available]. PMID- 20292596 TI - [Not Available]. PMID- 20292597 TI - [Not Available]. PMID- 20292598 TI - [Not Available]. PMID- 20292599 TI - [Not Available]. PMID- 20292600 TI - [Not Available]. PMID- 20292601 TI - [Not Available]. PMID- 20292602 TI - [Not Available]. PMID- 20292603 TI - [Not Available]. PMID- 20292604 TI - [Not Available]. PMID- 20292605 TI - [Not Available]. PMID- 20292606 TI - [Not Available]. PMID- 20292607 TI - [Not Available]. PMID- 20292608 TI - [Not Available]. PMID- 20292609 TI - [Not Available]. PMID- 20292610 TI - [Not Available]. PMID- 20292611 TI - [Not Available]. PMID- 20292612 TI - [Not Available]. PMID- 20292613 TI - [Not Available]. PMID- 20292614 TI - [Not Available]. PMID- 20292616 TI - [Not Available]. PMID- 20292615 TI - [Not Available]. PMID- 20292617 TI - [Not Available]. PMID- 20292618 TI - [Not Available]. PMID- 20292619 TI - [Not Available]. PMID- 20292620 TI - [Not Available]. PMID- 20292621 TI - [Not Available]. PMID- 20292623 TI - [Not Available]. PMID- 20292622 TI - [Not Available]. PMID- 20292624 TI - [Not Available]. PMID- 20292626 TI - [Not Available]. PMID- 20292625 TI - [Not Available]. PMID- 20292627 TI - [Not Available]. PMID- 20292628 TI - [Not Available]. PMID- 20292629 TI - [Not Available]. PMID- 20292630 TI - [Not Available]. PMID- 20292631 TI - [Not Available]. PMID- 20292632 TI - Lichen sclerosus et atrophicus with bullous lesions and extensive involvement; report of a case. PMID- 20292633 TI - Experiences in military dermatology; their interpretation in plans for improved general medical care. PMID- 20292634 TI - Moeller's glossitis; a case with remission during pregnancy. PMID- 20292635 TI - Tuberculoid leprosy of lupoid appearance. PMID- 20292636 TI - Reticulum, or lattice, fibers; further studies. PMID- 20292637 TI - Role of food allergy in eczematoid dermatitis. PMID- 20292638 TI - Basal squamous cell epithelioma associated with leukemia. PMID- 20292639 TI - Use of trichophytin in thromboangiitis obliterans. PMID- 20292640 TI - Cardiolipin-lecithin antigen; recent development toward a single standard test of the blood for syphilis. PMID- 20292641 TI - Sulfonamide psoriasiform dermatitis. PMID- 20292642 TI - Atypical lichen planus tropicalis. PMID- 20292643 TI - Xanthomatous biliary cirrhosis with flat xanthomas of the eyelids. PMID- 20292644 TI - Urticaria pigmentosa with bullae. PMID- 20292645 TI - [Not Available]. PMID- 20292646 TI - [Not Available]. PMID- 20292647 TI - Blastomycosis. PMID- 20292648 TI - [Not Available]. PMID- 20292649 TI - Idiopathic multiple hemorrhagic sarcoma (Kaposi). PMID- 20292650 TI - Disseminated subacute lupus erythematosus (?). PMID- 20292651 TI - Heat and emotional urticaria. PMID- 20292652 TI - Lichen nitidus. PMID- 20292653 TI - A case for diagnosis (neural leprosy?). PMID- 20292654 TI - Pellagra. PMID- 20292655 TI - Tuberculosis cutis orificialis with underlying pulmonary tuberculosis. PMID- 20292656 TI - Kerions. PMID- 20292657 TI - Chronic coccogenous sycosis treated locally with penicillin. PMID- 20292658 TI - Hodgkin's disease complicated by a squamous cell epithelioma of the neck. PMID- 20292659 TI - Idiopathic multiple pigmented sarcoma of Kaposi. PMID- 20292660 TI - Lichenoid dermatitis (New Guinea type). PMID- 20292661 TI - Syphilitic keratosis. PMID- 20292662 TI - A case for diagnosis (monocytic leukemia?). PMID- 20292663 TI - Unilateral ulceration of the mouth (tuberculosis orificialis?), probably with miliary and ileocecal involvement. PMID- 20292664 TI - Roentgen ray dermatitis treated with radon ointment. PMID- 20292665 TI - Dermatitis venenata due to a penicillin-containing ointment. PMID- 20292666 TI - Junction nevus. PMID- 20292667 TI - Morphea-like epithelioma and basal cell epithelioma of the face cured by roentgen ray therapy. PMID- 20292668 TI - Nummular eczema. PMID- 20292669 TI - Radiodermatitis of the dorsal surface of the hands. PMID- 20292670 TI - A case for diagnosis (poikiloderma atrophicans vasculare?). PMID- 20292671 TI - Parapsoriasis en gouttes. PMID- 20292672 TI - Poikiloderma vasculare atrophicans (Jacobi). PMID- 20292673 TI - Angioneurotic edema. PMID- 20292674 TI - Pemphigus vulgaris. PMID- 20292675 TI - Dermatofibroma (fibrosarcoma?). PMID- 20292676 TI - Hodgkin's disease of the skin without demonstrable systemic involvement. PMID- 20292677 TI - A case for diagnosis (leukemid? scabies?). PMID- 20292678 TI - Dermatitis herpetiformis caused by stasis dermatitis. PMID- 20292679 TI - Parasitic infection? scabies? PMID- 20292680 TI - Lupus vulgaris. PMID- 20292681 TI - NUCLEAR physics instruments for radiation measurements. PMID- 20292682 TI - NEW method for hydrofluoric acid determination is rapid and convenient. PMID- 20292683 TI - The stainability of nerve fibers by protargol with various fixatives and staining technics. PMID- 20292684 TI - The action of ribonuclease on fixed tissues. PMID- 20292685 TI - A confirmation of Rafalko's Feulgen method. PMID- 20292686 TI - Malt diast se and ptyalin in place of saliva in the identification of glycogen. PMID- 20292687 TI - Paraffin sections of tissue fragments. PMID- 20292688 TI - Bismarck brown as a stain for mucoproteins. PMID- 20292689 TI - Vitamin deficiency in nervous and mental disease; clinical studies. PMID- 20292690 TI - Microbiological methods for the estimation of amino acids. PMID- 20292691 TI - Nutrition in colonial territories. PMID- 20292692 TI - The colonial nutrition problem. PMID- 20292693 TI - Malnutrition in colonial territories. PMID- 20292694 TI - Relation of animal husbandry to human nutritional needs. PMID- 20292695 TI - Nutrition in colonial territories; sociological factors. PMID- 20292696 TI - The role of nutrition in social medicine. PMID- 20292697 TI - Some observations on the nutrition of mothers and young children during the war years. PMID- 20292698 TI - On the difficulty of isolating the nutritional factor in disease from other factors in the social background. PMID- 20292699 TI - Nutrition in India during and after the war. PMID- 20292700 TI - Poverty lines and standards of living. PMID- 20292701 TI - Nutritional experiences in prisoner of war and internment camps in the Far East. PMID- 20292702 TI - Nutritional conditions in army prison camps in the Far East. PMID- 20292703 TI - Nutritional conditions and diseases in the civilian internment camp, Hong Kong. PMID- 20292704 TI - Experiences in the civilian camp at Singapore. PMID- 20292705 TI - Experiences in the military camp at Singapore. PMID- 20292706 TI - Experiences in the military camp at Singapore. PMID- 20292707 TI - Nutritional conditions among women and children in internment in the civilian camp at Singapore. PMID- 20292708 TI - [Not Available]. PMID- 20292709 TI - [Not Available]. PMID- 20292710 TI - [Not Available]. PMID- 20292711 TI - The limitations of roentgenology and gastroscopy in the diagnosis of diseases of the stomach; an analysis of fifty-three proven cases. PMID- 20292712 TI - The value of gastroscopy to the clinician. PMID- 20292713 TI - The gastroscopic differentiation of gastritis from carcinoma of the stomach. PMID- 20292714 TI - Metabolic disturbances in workers exposed to dinitrotoluene during World War II. PMID- 20292715 TI - Hepatitis following transfusion. PMID- 20292716 TI - Epidemic hepatitis. PMID- 20292717 TI - Amebic liver abscess in service personnel. PMID- 20292718 TI - Observations on 543 cases of peptic ulcer. PMID- 20292719 TI - A study of the gastric secretory response in the aged. PMID- 20292720 TI - Apparent lack of relationship between levels of B-vitamins in the feces and dietary supplementation with crystalline B-vitamins and protein. PMID- 20292721 TI - A paracolon organism antigenically related to the Sachs Q-1030 bacillus and associated with chronic enterocolitis. PMID- 20292722 TI - Massive gastric hemorrhage associated with aberrant pancreas in the stomach. PMID- 20292723 TI - BRUCELLOSIS versus neurosis; an attempt at an appraisal. PMID- 20292724 TI - Serum gonadotrophin in Welsh and Shetland ponies. PMID- 20292725 TI - The measurement of lactational performances in the rat in studies of the endocrine control of lactation. PMID- 20292726 TI - Adrenalectomy and replacement therapy in lactating rats; effects of deoxycorticosterone acetate on lactation in adrenalectomized rats. PMID- 20292727 TI - Adrenalectomy and replacement therapy in lactating rats; effects of deoxycorticosterone acetate and 11-oxygenated cortical steroids on lactation in adrenalectomized rats maintained on stock or high-protein diets. PMID- 20292728 TI - Late effects of castration and aministration of sex hormones on the male Trichosurus vulpecula. PMID- 20292729 TI - The possibility of determining androgen production by measuring the acid phosphatase in semen; investigations in cryptorchid patients. PMID- 20292730 TI - The antigenic properties of iodinated proteins. PMID- 20292731 TI - Notes on the German legal and penal system. PMID- 20292733 TI - Scientific parole, a proposal. PMID- 20292732 TI - A plea for selective psychiatric treatment for offenders. PMID- 20292734 TI - The success and failure of 926 naval offenders. PMID- 20292735 TI - Convicting the innocent [due to his supposed similarity in appearance to the person guilty]. PMID- 20292736 TI - Admissibility in evidence of scientific tests for alcoholic intoxication. PMID- 20292738 TI - Genetics of natural populations; a response of certain gene arrangements in the third chromosome of Drosophila pseudoobscura to natural selection. PMID- 20292744 TI - A wildfire resistant tobacco. PMID- 20292745 TI - Diet-induced feather modification in the fowl; sickle and feather growth in thiouracil-treated and in Japanese long-tailed chickens. PMID- 20292746 TI - PUERTO RICO marches on. PMID- 20292747 TI - Zygodactyly and associated variations in a Utah family. PMID- 20292748 TI - [Not Available]. PMID- 20292749 TI - [Not Available]. PMID- 20292751 TI - [Not Available]. PMID- 20292750 TI - [Not Available]. PMID- 20292752 TI - [Not Available]. PMID- 20292753 TI - [Not Available]. PMID- 20292754 TI - [Not Available]. PMID- 20292755 TI - [Not Available]. PMID- 20292756 TI - [Not Available]. PMID- 20292757 TI - [Not Available]. PMID- 20292758 TI - [Not Available]. PMID- 20292759 TI - [Not Available]. PMID- 20292760 TI - [Not Available]. PMID- 20292761 TI - [Not Available]. PMID- 20292762 TI - [Not Available]. PMID- 20292763 TI - [Not Available]. PMID- 20292764 TI - [Not Available]. PMID- 20292765 TI - [Not Available]. PMID- 20292766 TI - [Not Available]. PMID- 20292767 TI - [Not Available]. PMID- 20292768 TI - [Not Available]. PMID- 20292769 TI - [Not Available]. PMID- 20292770 TI - [Not Available]. PMID- 20292771 TI - Local infiltration anesthesia in obstetrics and gynecology. PMID- 20292772 TI - Achondroplasia. PMID- 20292773 TI - [Not Available]. PMID- 20292774 TI - [Not Available]. PMID- 20292775 TI - [Not Available]. PMID- 20292776 TI - [Not Available]. PMID- 20292777 TI - [Not Available]. PMID- 20292778 TI - [Not Available]. PMID- 20292780 TI - Nationalism and internationalism in medicine. PMID- 20292779 TI - [Not Available]. PMID- 20292781 TI - John Hunter, Sir Thomas Browne and the experimental method. PMID- 20292782 TI - The exclusion of aliens from the United States for physical defects. PMID- 20292783 TI - Studies on mortality since the Renaissance. PMID- 20292784 TI - A merry medicine for the teeth (ca. 1520). PMID- 20292785 TI - An agricultural research library. PMID- 20292786 TI - [Not Available]. PMID- 20292787 TI - Clinical study of fractures of the carpal scaphoid bone. PMID- 20292788 TI - Newer aspects of the surgical approach to abdominal disease. PMID- 20292789 TI - Some interesting experiences with homoeopathy by a specialist. PMID- 20292790 TI - The value of eclectic therapy in chronic diseases. PMID- 20292791 TI - Triumphs and errors of modern medicine; a practical way out of the dilemma. PMID- 20292792 TI - New drugs. PMID- 20292793 TI - ST. THOMAS'S Hospital, London. PMID- 20292794 TI - Bedpan washers and sterilisers. PMID- 20292795 TI - TEXAS Medical Center to benefit from $160,000,000 Cullen gift. PMID- 20292796 TI - The ideal Catholic nurse. PMID- 20292797 TI - An interpretation of the analysis of the practical nurse occupation. PMID- 20292798 TI - Dissatisfied hospital workers. PMID- 20292799 TI - Public relations of the Catholic hospital. PMID- 20292800 TI - Maintenance and safety in hospitals. PMID- 20292801 TI - Intensifying the Catholic atmosphere of the hospital. PMID- 20292802 TI - Hospital sisters tackle the problem. PMID- 20292803 TI - The regulations for the administration of the Federal Hospital Survey and Construction Act. PMID- 20292804 TI - Encephalography and ventriculography. PMID- 20292805 TI - The orthopedic fracture, and neurosurgical patients. PMID- 20292806 TI - Digesters for tubercle bacilli specimens. PMID- 20292807 TI - New law suits affecting hospitals. PMID- 20292808 TI - The safety of air deodorants. PMID- 20292809 TI - Sanatorium design; planning of a 320 bed unit for pulmonary tuberculosis. PMID- 20292810 TI - International hospital research and information. PMID- 20292811 TI - Administrative staff salaries. PMID- 20292812 TI - Keeping Britain's blood banks supplied. PMID- 20292813 TI - Legal implications of the general duty nurse. PMID- 20292814 TI - Psychiatry for 20 million veterans. PMID- 20292815 TI - Services for the blind: vocational rehabilitation. PMID- 20292816 TI - Clinical psychology as a psychodiagnostic art. PMID- 20292817 TI - Psychologist and psychiatrist. PMID- 20292819 TI - The diagnosis of a patient with organic defect. PMID- 20292818 TI - The diagnosis of a patient with limited capacity. PMID- 20292820 TI - The dynamics of an amnesic personality. PMID- 20292821 TI - Differences in parent behavior toward three- and nine-year-old children. PMID- 20292822 TI - A validation study of the Rotter-Jensen level of aspiration test. PMID- 20292823 TI - An experimental investigation of neuroticism. PMID- 20292824 TI - Nutrition in childhood. PMID- 20292825 TI - The economics of appetite. PMID- 20292826 TI - A simple rating device. PMID- 20292827 TI - How to develop successful office supervisors. PMID- 20292828 TI - Old and new economic doctrines. PMID- 20292829 TI - Can social science be scientific and social? PMID- 20292830 TI - Who is the juvenile delinquent? PMID- 20292831 TI - First session of UN's permanent Social Commission. PMID- 20292832 TI - The new British system of social security. PMID- 20292833 TI - Industrial ventilation. PMID- 20292834 TI - Studies on infection with Bacillus anthracis; the isolation of an inflammatory factor from crude extracts of lesions of B. anthracis infection and its biological and chemical relationship to glutamyl polypeptide. PMID- 20292835 TI - Studies on infection with Bacillus anthracis; physiological changes in experimental animals during the course of infection with B. anthracis. PMID- 20292836 TI - Studies on infection with Bacillus anthracis; a comparison of the antibacterial effects of calf thymus histone and a quarternary ammonium cationic detergent on B anthracis. PMID- 20292837 TI - Reticulo-endothelial immune serum (REIS); an experimental anemia in Bartonella infected rats produced by anti-blood immune serum. PMID- 20292838 TI - Studies on haemoflagellates: a semi-solid medium and a fluid medium with a solid base for growing various species of Leishmania and Trypanosoma cruzi. PMID- 20292839 TI - Studies on haemoflagellates; a study of the growth rates of Leishmania donovani, L. brasiliensis, L. tropica, and Trypanosoma cruzi in culture. PMID- 20292840 TI - On the occurrence in human serum of an inhibitory substance to hyaluronidase produced by a strain of hemolytic streptococcus. PMID- 20292841 TI - The evaluation of germicidal agents by an infection prevention-toxicity method. PMID- 20292842 TI - Inactivation of murine poliomyelitis viruses by heat. PMID- 20292843 TI - The morphology of cryptozoites and metacryptozoites of Plasmodium relictum and the relationship of these stages to parasitemia in canaries and pigeons. PMID- 20292844 TI - Skin tests in schistosomiasis mansoni with antigen from heterologous worms (Pneumoneces; Planaria). PMID- 20292845 TI - Performance of aerial spray equipment used to disperse DDT at Orlando, Florida; summary. PMID- 20292846 TI - Observations on mosquito and malaria control in the Caribbean area; Suriname. PMID- 20292847 TI - Experiments with weed-killers against salt marsh plants which hinder mosquito control operations. PMID- 20292848 TI - The possible endemicity of Anopheles albimanus in Florida. PMID- 20292849 TI - Psorophora pygmaea (Theobald), an exotic mosquito now established in Florida. PMID- 20292850 TI - Banishing bug bites. PMID- 20292851 TI - Studies on filariasis in Papua, New Guinea. PMID- 20292852 TI - Occurrence of Anopheles atropos in Jamaica, B. W. I. PMID- 20292853 TI - Should mosquito commissions undertake other insect control problems requiring community effort? PMID- 20292854 TI - The determination of cardiac efficiency and its clinical significance. PMID- 20292855 TI - Intravenous administration of histamine in oto-rhinology. PMID- 20292856 TI - Pneumoperiton eum by pylorostenosis; report of two cases. PMID- 20292857 TI - Polycystic kidney and cholera in an East African Negro. PMID- 20292858 TI - The influence of complications on the treatment of peptic ulcer. PMID- 20292859 TI - Amino acids in nephrosis. PMID- 20292860 TI - The recognition of acute bacterial endocarditis. PMID- 20292861 TI - Short-term psychotherapy. PMID- 20292862 TI - Edema in chronic nephritis; its mechanism and management. PMID- 20292863 TI - Rocky Mountain spotted fever. PMID- 20292864 TI - Differential diagnosis and symptomatic treatment in the asthmatic patient. PMID- 20292865 TI - Esophageal varices. PMID- 20292867 TI - Recurrent Graves' disease? PMID- 20292866 TI - Constrictive pericarditis? PMID- 20292868 TI - Diffuse carcinomatosis of lungs and subacute cor pulmonale. PMID- 20292869 TI - [Encephalomalacia; right occipital lobe, recent; left occipital lobe, old]. PMID- 20292870 TI - Medical research in the USSR. PMID- 20292871 TI - Research program of the U.S. Public Health Service. PMID- 20292872 TI - Health in Byelorussia, a devastated area of the Soviet Union. PMID- 20292873 TI - Microbiology in the Soviet Union. PMID- 20292874 TI - Experimental cancer research in the USSR. PMID- 20292875 TI - Radiotherapy of malignant tumors in the USSR. PMID- 20292877 TI - Cancer prevention and control in the USSR. PMID- 20292876 TI - Cancer as a systemic disease. PMID- 20292878 TI - The organization of a cancer research institute. PMID- 20292879 TI - Recent advances in Soviet neurology. PMID- 20292880 TI - [Not Available]. PMID- 20292881 TI - [Not Available]. PMID- 20292882 TI - [Not Available]. PMID- 20292883 TI - [Not Available]. PMID- 20292884 TI - [Not Available]. PMID- 20292885 TI - [Not Available]. PMID- 20292886 TI - [Not Available]. PMID- 20292887 TI - [Not Available]. PMID- 20292888 TI - [Not Available]. PMID- 20292889 TI - Physicians of the machine age. PMID- 20292890 TI - Rheumatic pneumonia. PMID- 20292891 TI - Bronchial spasm in cardiac asthma. PMID- 20292892 TI - The use of methyl-iso-octenylamine in migraine. PMID- 20292893 TI - Brucella sensitization; a clinical evaluation. PMID- 20292894 TI - Hepatic cirrhosis as a complication of chronic ulcerative colitis. PMID- 20292895 TI - Cardiologic criteria for the diagnosis of rheumatic heart disease in the apparently healthy subject. PMID- 20292897 TI - Prescription of physical medicine by the internist. PMID- 20292896 TI - The action of carbon dioxide in water mobilization. PMID- 20292898 TI - Bronchopulmonary actinomycosis. PMID- 20292899 TI - Banti's syndrome with multiple aneurysms and thromboses of the splenic blood vessels. PMID- 20292900 TI - Waterhouse-Friderichsen syndrome; recovery from shock in fatal case. PMID- 20292901 TI - Fatality in a blood donor; a case report, with a review of the literature. PMID- 20292902 TI - Fatal spontaneous hemopneumothorax; review of the literature and report of a case. PMID- 20292903 TI - Gold salts for rheumatoid arthritis. PMID- 20292904 TI - [Not Available]. PMID- 20292905 TI - [Not Available]. PMID- 20292906 TI - [Not Available]. PMID- 20292907 TI - [Not Available]. PMID- 20292908 TI - [Not Available]. PMID- 20292910 TI - [Not Available]. PMID- 20292909 TI - [Not Available]. PMID- 20292911 TI - [Not Available]. PMID- 20292912 TI - [Not Available]. PMID- 20292913 TI - [Not Available]. PMID- 20292914 TI - [Not Available]. PMID- 20292916 TI - [Not Available]. PMID- 20292915 TI - [Not Available]. PMID- 20292917 TI - [Not Available]. PMID- 20292918 TI - Sidelights on hypnotism. PMID- 20292920 TI - Splenomegaly. PMID- 20292919 TI - THE Department of Medical Photography. PMID- 20292921 TI - Faecal urobilinogen in disease. PMID- 20292922 TI - Diarrhoea. PMID- 20292923 TI - Progressive muscular atrophy; and other conditions of muscular wasting. PMID- 20292924 TI - [Not Available]. PMID- 20292925 TI - [Not Available]. PMID- 20292926 TI - [Not Available]. PMID- 20292927 TI - [Not Available]. PMID- 20292928 TI - [Not Available]. PMID- 20292929 TI - [Not Available]. PMID- 20292930 TI - [Not Available]. PMID- 20292931 TI - [Not Available]. PMID- 20292932 TI - Diverticulum of the pars media of the stomach. PMID- 20292933 TI - Cysts of the pancreas; report of a case successfully marsupialized during pregnancy. PMID- 20292934 TI - Survey of the efficiency of cultures and guinea pig inoculations in the diagnosis of tuberculosis. PMID- 20292935 TI - Siderofibrosis of the spleen secondary to sickle-cell anemia (three case reports. PMID- 20292936 TI - A case of chylothorax and chylous ascites with a review of lesions of the thoracic duct. PMID- 20292937 TI - Malignant osseous tumors of the jaw; three case reports. PMID- 20292938 TI - Arsphenamine encephalopathy. PMID- 20292939 TI - Morton's metatarsalgia. PMID- 20292940 TI - Septicemia and bacteremia. PMID- 20292941 TI - Rheumatic fever. PMID- 20292942 TI - Osteoid osteoma. PMID- 20292943 TI - Salmonella meningitis; report of a case treated with streptomycin. PMID- 20292944 TI - Myocardial infarction without coronary occlusion. PMID- 20292945 TI - The fenestration operation for progressive deafness. PMID- 20292946 TI - Aspiration curettage in a cancer clinic; an analysis of 200 cases. PMID- 20292947 TI - Porphyria. PMID- 20292948 TI - Compulsory insurance and public health; inferior medical service and rackets. PMID- 20292949 TI - Local treatment of dog bites; a new method. PMID- 20292950 TI - The present status of vaccination against tuberculosis with B. C. G. PMID- 20292951 TI - The medical care of veterans. PMID- 20292952 TI - Clinical characteristics of essential hypertension in relation to prognosis with a comparison of the effectiveness of medical and of surgical treatment. PMID- 20292953 TI - Anesthesiology as an integral part of medical education. PMID- 20292954 TI - Eczematoid dermatoses in childhood. PMID- 20292955 TI - Early diagnosis of carcinoma of the lung. PMID- 20292956 TI - British medical man makes broad consideration from standpoints of physician and patient. PMID- 20292957 TI - Types and mechanism of cardiac dyspnea. PMID- 20292958 TI - The history of the microscope and early microscopy. PMID- 20292959 TI - The patient-physician relationship. PMID- 20292960 TI - American spas in historical perspective. PMID- 20292961 TI - Carnival week-end at Dartmouth. PMID- 20292962 TI - Is man's useful life ended at 65? PMID- 20292963 TI - The history of medicine as a hobby; a collection of medical classics. PMID- 20292964 TI - The early diagnosis of malignant disease of the ear, nose and throat. PMID- 20292965 TI - Malignant tumour of the suprarenal gland with paroxysmal high tension. PMID- 20292966 TI - Embolic occlusion in rheumatic endocarditis. PMID- 20292967 TI - The treatment of chronic cholecystitis. PMID- 20292969 TI - The family physician is necessary. PMID- 20292968 TI - Immunity. PMID- 20292970 TI - Acute glomerulonephritis; a review of 90 cases. PMID- 20292971 TI - Erythroblastosis due to A-O incompatibility. PMID- 20292972 TI - Sub-aortic stenosis. PMID- 20292973 TI - Acute appendicitis simulating rheumatic fever. PMID- 20292974 TI - Sodium restriction in the diet for hypertension. PMID- 20292975 TI - Thrombosis of the lower extremity; consideration of anti-embolic management. PMID- 20292976 TI - Isolated xanthomata. PMID- 20292977 TI - Obscure cause of fever in a diabetic; case report. PMID- 20292978 TI - Accessory ureter with abnormal implantation; case report. PMID- 20292979 TI - Calcareous valvular heart disease; case report. PMID- 20292980 TI - Uveitis. PMID- 20292981 TI - Malpractice prophylaxis. PMID- 20292982 TI - Prolapsed intervertebral disc. PMID- 20292983 TI - Pneumoperitoneum in the treatment of pulmonary tuberculosis. PMID- 20292984 TI - Sequelae of tropical disease, skin conditions. PMID- 20292985 TI - Sequelae of tropical disease. PMID- 20292986 TI - Chemical factors in pernicious anaemia. PMID- 20292987 TI - Financial support of medical education. PMID- 20292988 TI - Researches on the chemotherapy of malaria; the biological approach. PMID- 20292989 TI - Researches on the chemotherapy of malaria; the chemical approach. PMID- 20292990 TI - Kala-azar; a description of four cases occurring in a Glasgow hospital. PMID- 20292991 TI - Case report of toxic perforation of the jejunum. PMID- 20292992 TI - Nerve injuries affecting the hand. PMID- 20292993 TI - A case of neurofibroma of the stomach. PMID- 20292994 TI - Roentgenology at Harvard. PMID- 20292995 TI - Remarks about the application of the betatron in cancer therapy. PMID- 20292996 TI - Conservative renal surgery. PMID- 20292997 TI - The relation of the near point convergence to squint surgery. PMID- 20292998 TI - A plan of cooperation between county health departments and tuberculosis sanatorium boards. PMID- 20292999 TI - The brain in infantile cerebral palsy. PMID- 20293000 TI - The expression of dosage in X-ray and radium therapy. PMID- 20293001 TI - Observations on malnutrition in Santo Tomas Internment Camp. PMID- 20293002 TI - Modern concept of heredity. PMID- 20293003 TI - Large glioma of the superior vermis of the cerebellum. PMID- 20293004 TI - Tuberculosis ulceration of the terminal ileum, ileo-caecal valve and ascending colon. PMID- 20293005 TI - Spontaneous rupture of a large aneurysm of the left middle cerebral artery. PMID- 20293006 TI - Observations on emaciation states. PMID- 20293007 TI - Anthropology in medicine. PMID- 20293009 TI - Intestinal obstruction. PMID- 20293008 TI - Antithyroid compounds and their clinical uses. PMID- 20293010 TI - The management of urticaria due to penicillin. PMID- 20293011 TI - The problem of venous thrombosis. PMID- 20293012 TI - Heparin in the treatment of thromboembolic disease. PMID- 20293013 TI - Venous thrombosis and pulmonary embolism. PMID- 20293014 TI - The treatment of serum sickness with benadryl. PMID- 20293015 TI - Methemoglobinemia in an infant as a result of the administration of bismuth subnitrate. PMID- 20293016 TI - The trend toward labor health and welfare programs. PMID- 20293017 TI - The surgical treatment of essential hypertension. PMID- 20293018 TI - Medical evaluation of the surgical treatment of hypertension. PMID- 20293019 TI - General practice in a large hospital. PMID- 20293020 TI - Intrathecal penicillin. PMID- 20293021 TI - Synthetic folic acid; the effectiveness of a conjugated form in the treatment of tropical sprue, addisonian pernicious anemia and nutritional macrocytic anemia. PMID- 20293023 TI - MALPRACTICE: physician's liability for burns received during operation [Mass., 1946]. PMID- 20293022 TI - Pancreolithiasis and chronic pancreatitis; preliminary report of a case of apparently successful treatment by transthoracic sympathectomy and vagectomy. PMID- 20293024 TI - Rapid identification of Shigella in a public health laboratory. PMID- 20293025 TI - The serologic response in murine typhus as measured by the Weil-Felix, rickettsial complement fixation, and rickettsial agglutination reactions. PMID- 20293026 TI - Influenza B in Needham, Massachusetts, December, 1945; serologic studies in cases and in family contacts. PMID- 20293027 TI - The effect of antihistamine drugs upon serum-induced myocarditis in rabbits. PMID- 20293028 TI - Evidence for the activity of a second member of the vitamin M group (fermentation factor) in sprue; a case report. PMID- 20293029 TI - Thiouracil and propylthiouracil; a comparative clinical study. PMID- 20293030 TI - Observations on the diurnal excretion of urobilinogen in the urine of normal subjects and of patients with Laennec's cirrhosis. PMID- 20293031 TI - A comparison of the nutritive value of the proteins in mixed diets for dogs, rats, and human beings. PMID- 20293032 TI - Prothrombin time studies on human beings and experimental animals. PMID- 20293033 TI - The corpuscular constants of college women of the North Central states. PMID- 20293034 TI - Two popular fallacies regarding Rh; preliminary report of some thought-provoking observations. PMID- 20293035 TI - Metabolic complexities of pellagra. PMID- 20293036 TI - Nitrogen balance. PMID- 20293037 TI - Assay of penicillin, streptomycin, trivalent organic arsenicals, and other bactericidal and bacteriostatic agents; a technique based on an original application of mathematical principles with adaptations for all assay purposes. PMID- 20293039 TI - Peptic ulcer; a review of present-day treatment. PMID- 20293038 TI - An experimental method for obtaining an ultrafiltrate of the blood. PMID- 20293041 TI - Surgery on elderly patients. PMID- 20293040 TI - Thiouracil in the treatment of toxic goiter, and its dangers. PMID- 20293042 TI - Subphrenic abscess. PMID- 20293043 TI - Topical application of thrombin and plasma in split skin grafts. PMID- 20293044 TI - The present status of pilonidal cysts. PMID- 20293045 TI - The importance of early diagnosis of bladder tumors. PMID- 20293046 TI - Spinal anesthesia. PMID- 20293047 TI - Further consideration of malignant lymphoma. PMID- 20293048 TI - Surgery of the colon in wartime; experiences in the management of reconstruction of the colon in Z. I. hospitals. PMID- 20293049 TI - The overweight obstetric patient with special reference to the use of dexedrine sulfate. PMID- 20293050 TI - Choice of carbohydrates used in artificial feeding of infants. PMID- 20293051 TI - Infectious mononucleosis: benign lymphadenosis of glandular fever. PMID- 20293052 TI - So your Ob is Rh negative? PMID- 20293053 TI - Epidemic diarrhea of the newborn. PMID- 20293055 TI - The problem of varicose veins. PMID- 20293054 TI - Bone lesions in Gaucher's disease. PMID- 20293056 TI - Some unusual complications of diphtheria. PMID- 20293057 TI - Clinical approach to preventive medicine. PMID- 20293058 TI - Calciferol in tuberculosis; review of 150 cases of lupus vulgaris. PMID- 20293059 TI - Sand-fly fever; review of 664 cases. PMID- 20293060 TI - Parahaemophilia; haemorrhagic diathesis due to absence of a previously unknown clotting factor. PMID- 20293061 TI - Effect of water on gastric motility; a test for duodenal ulcer. PMID- 20293062 TI - Tubal patency tests. PMID- 20293063 TI - Amyloid macroglossia. PMID- 20293064 TI - Joint changes in cancer of the lung. PMID- 20293065 TI - Infantile insomnia and maternal Graves' disease. PMID- 20293066 TI - Stevens-Johnson syndrome. PMID- 20293067 TI - Recurrent shoulder dislocation. PMID- 20293068 TI - Temporary hypertension after curare. PMID- 20293069 TI - Symposium on diabetes. PMID- 20293070 TI - Does hyperglycemia harm the diabetic patient? PMID- 20293071 TI - Treatment of the child with diabetes mellitus. PMID- 20293072 TI - Symptomless glycosurias; differentiation by sugar tolerance tests. PMID- 20293073 TI - Interpretation of glucose tolerance tests. PMID- 20293074 TI - The diagnosis of the less common meliturias; including pentosuria and fructosuria. PMID- 20293075 TI - Effective insulin timing in diabetes mellitus. PMID- 20293076 TI - Insulin mixtures and modifications. PMID- 20293077 TI - Unusual requirements for insulin; resistance, refractoriness, insensitivity to insulin. PMID- 20293078 TI - Recent statistics on diabetes and diabetics. PMID- 20293079 TI - Incentives to the treatment of diabetes mellitus. PMID- 20293080 TI - Pregnancy complicating diabetes of more than 20 years' duration. PMID- 20293081 TI - Some considerations of acute complications of diabetes. PMID- 20293082 TI - Clinical implications of alloxan diabetes. PMID- 20293083 TI - Summer camps for diabetic children. PMID- 20293084 TI - Diabetic acidosis and coma. PMID- 20293085 TI - Treatment of diabetic coma and pre-coma; coma complicated by bacteremia and gangrene; pre-coma associated with lipemia retinalis. PMID- 20293086 TI - Hyperinsulinism among malingerers. PMID- 20293087 TI - Diabetes and public health. PMID- 20293088 TI - The American Diabetes Association. PMID- 20293089 TI - Recent advances in surgery in relation to general practice. PMID- 20293090 TI - Pitfalls in the diagnosis and treatment of some common dermatoses. PMID- 20293091 TI - Veins and varicosities. PMID- 20293092 TI - Nostalgic reminiscence of a family physician. PMID- 20293093 TI - A five year study of extrauterine pregnancy. PMID- 20293094 TI - Deep circulation and the treatment of varicose veins. PMID- 20293095 TI - England's pioneer of preventive inoculation. PMID- 20293096 TI - Management of arthritis in the menopause. PMID- 20293097 TI - Rectal medication with emphasis on its worth and noting its practicality. PMID- 20293098 TI - Venereal disease control. PMID- 20293099 TI - The modern treatment of gonorrhea. PMID- 20293101 TI - The treatment of syphilis. PMID- 20293100 TI - Diagnosis and treatment of chancroid, lymphopathia venereum, and granuloma inguinale. PMID- 20293102 TI - Oral smears; an index to hormone stimulation. PMID- 20293103 TI - Paediatrics at the Middlesex Hospital. PMID- 20293104 TI - Peritoneoscopy. PMID- 20293105 TI - Local anaesthesia. PMID- 20293106 TI - Gamma globulin as a prophylactic and therapeutic agent in communicable disease. PMID- 20293107 TI - Peritoneal adhesions. PMID- 20293108 TI - Neurosyphilis control program in Mississippi. PMID- 20293109 TI - Some facts about allergy that should be known. PMID- 20293110 TI - Plans for an intensified tuberculosis case-finding program in Mississippi. PMID- 20293111 TI - The use of curare in anesthesia. PMID- 20293112 TI - Experiences with curare in anesthesia. PMID- 20293113 TI - Carcinoma of the breast; a review of the first three years' experience in the cancer section of the Westfield State Sanatorium. PMID- 20293114 TI - Multiple congenital defects following maternal varicella; report of a case. PMID- 20293115 TI - Effects of protein deficiency on the pregnant woman and fetus and on the infant and child. PMID- 20293116 TI - [Basalcell papilloma of bronchus, with cornification]. PMID- 20293117 TI - [Carcinoma of common bile duct]. PMID- 20293118 TI - Treatment of hyperthyroidism. PMID- 20293119 TI - Social and environmental factors in the practice of medicine. PMID- 20293120 TI - Men in medicine in Italy today, as I saw them. PMID- 20293121 TI - Laboratory and clinical criteria of rheumatic carditis in children. PMID- 20293122 TI - Effect of ultraviolet air sterilization upon incidence of respiratory infections in a children's institution; a 6-year study. PMID- 20293123 TI - A new rickettsial illness occurring in New York City; supplementary report. PMID- 20293124 TI - The growth of the Bellevue schools of nursing. PMID- 20293125 TI - The last century of medicine in New York. PMID- 20293126 TI - Duodenal ulcer; a constructive criticism of conservative therapy. PMID- 20293127 TI - Hirschsprung's disease or megacolon. PMID- 20293129 TI - Fatal complications of otitis media. PMID- 20293128 TI - A case of developmental inhibitions and herniation of the ovaries. PMID- 20293130 TI - Laminectomy. PMID- 20293131 TI - Primary sarcoma of bone; analysis of 71 cases. PMID- 20293132 TI - Renal infections; their etiology, diagnosis, and management. PMID- 20293133 TI - The recognition and treatment of venous thrombosis (phlebothrombosis and thrombophlebitis) with particular reference to the prevention of pulmonary embolism. PMID- 20293134 TI - Present-day concepts of the psychoneuroses. PMID- 20293136 TI - The seeds of immaturity. PMID- 20293135 TI - The electic approach in the treatment of the neuroses. PMID- 20293137 TI - Nontuberculous pulmonary calcification and histoplasmin sensitivity. PMID- 20293139 TI - Adenoidectomy vs. adenoidotomy. PMID- 20293138 TI - Physical therapy, rehabilitation, and occupational therapy in surgery. PMID- 20293140 TI - Psychosomatic medicine. PMID- 20293141 TI - Nutritional integration. PMID- 20293142 TI - Modern state health administration. PMID- 20293143 TI - The physician looks to improved public health administration in Pennsylvania. PMID- 20293144 TI - Administrative problems of the state health department. PMID- 20293145 TI - Modern trends in the management of uterine carcinoma. PMID- 20293146 TI - Suggested methods for the control of the present epidemic of tinea of the scalp. PMID- 20293148 TI - Physical medicine in pediatrics. PMID- 20293147 TI - Penicillin treatment of acute middle ear and mastoid infections. PMID- 20293149 TI - Dermatologic problems in the returning veteran. PMID- 20293150 TI - Carcinoma of the renal pelvic and ureter; the etiology and treatment. PMID- 20293151 TI - Hyperthyroidism without goiter, with reference to the use of propylthiouracil. PMID- 20293152 TI - Postmenopausal bleeding. PMID- 20293153 TI - Liver function tests. PMID- 20293154 TI - Radium therapy to nasopharynx for peri-tubal lymphoid tissue. PMID- 20293155 TI - Clinical experiences with benadryl in allergic states. PMID- 20293156 TI - Malaria; some practical considerations. PMID- 20293157 TI - Glaucoma, the treacherous; a brief outline of the treatment. PMID- 20293158 TI - Pregnancy complicating diabetes. PMID- 20293159 TI - A glaucoma clinic; its need, organization, and early growth. PMID- 20293160 TI - Adequate diphtheria immunization in a community. PMID- 20293161 TI - Primary carcinoma of the ureter. PMID- 20293162 TI - Recent advances in syphilologic diagnosis and treatment; the nonspecific positive serologic test and the use of penicillin. PMID- 20293163 TI - Delayed ligation of the umbilical cord. PMID- 20293164 TI - Common misconceptions of ocular disturbances in children. PMID- 20293165 TI - Nodular goiter and cancer of the thyroid. PMID- 20293166 TI - The child adapts to reality. PMID- 20293167 TI - Benign prostatic obstruction. PMID- 20293168 TI - The diagnosis and treatment of glycosuria. PMID- 20293170 TI - The diagnosis of nervous diseases. PMID- 20293169 TI - Nerve suture. PMID- 20293172 TI - Two cases of chylous effusion. PMID- 20293173 TI - Bronchoscopy in children; presentation of seven cases. PMID- 20293171 TI - The relationship of the medical student to the university. PMID- 20293174 TI - Some principles of anorectal surgery. PMID- 20293175 TI - Hyperparathyroidism resulting from a parathyroid adenoma; case report with discussion. PMID- 20293176 TI - Carcinoma of the adrenal cortex; a case report. PMID- 20293177 TI - Clot retraction; time and adequacy. PMID- 20293178 TI - Dermoid cyst of ovary containing a structure similar to a human body (homunculus). PMID- 20293179 TI - Drug therapy in peptic ulcer and hypersecretion. PMID- 20293180 TI - Poliomyelitis. PMID- 20293181 TI - Principles of orthopedic treatment in poliomyelitis. PMID- 20293182 TI - The ill-effects of nicotinic acid. PMID- 20293183 TI - Diverticulitis of the sigmoid. PMID- 20293184 TI - Experimental studies on diagnosis and treatment of herpes simplex. PMID- 20293185 TI - Progress in the treatment of bronchial asthma. PMID- 20293186 TI - Postmenopausal pruritus vulvae. PMID- 20293187 TI - A few instances of unsuspected antenatal disease. PMID- 20293188 TI - Viruses and virus diseases. PMID- 20293189 TI - The physical and physiologic basis of alpha ray therapy. PMID- 20293190 TI - Corpuscular radiation (radon ointment and radium pads) in treatment of skin diseases. PMID- 20293191 TI - Radiation therapy with corpuscular rays. PMID- 20293192 TI - Minor psychotherapy. PMID- 20293193 TI - Psychotherapeutic emergency situations. PMID- 20293194 TI - Minor psychotherapy in cardiovascular disturbances. PMID- 20293195 TI - Minor psychotherapy in gastrointestinal disorders. PMID- 20293196 TI - Psychotherapy in gastrointestinal disorders. PMID- 20293197 TI - Findings of parasites in surgical pathology material; some pertinent diagnostic problems. PMID- 20293198 TI - Newer concepts of eosinophilia. PMID- 20293199 TI - Trichinosis. PMID- 20293200 TI - Observations concerning toxo plasma. PMID- 20293201 TI - Heart disease erroneously diagnosed (parasternal diaphragmatic hernia, imitating heart disease). PMID- 20293202 TI - An unusual cause for severe carotid sinus syndrome. PMID- 20293203 TI - Roentgenological evidence of appendiceal abscesses. PMID- 20293204 TI - A case of phantom eye. PMID- 20293205 TI - Frontal lobectomy as therapeutic attempt in mental disease. PMID- 20293206 TI - Half a century of roentgen rays. PMID- 20293207 TI - Comparative geographical pathology of Venezuela. PMID- 20293208 TI - Dietary production of gastric ulcers in rats and prevention by tocopherol administration. PMID- 20293209 TI - Nature of renal changes in acute choline deficiency. PMID- 20293210 TI - Reticulo-endothelial immune serum (REIS); production of potent serum by anamnestic reaction. PMID- 20293211 TI - Effects of benadryl on anaphylactic and histamine shock in rabbits and guinea pigs. PMID- 20293212 TI - Methionine decholesterolization in old hens. PMID- 20293213 TI - Fibrinogenolytic demonstration of activation and inhibition of tryptase in plasma protein fraction-I (antihemophilic globulin). PMID- 20293214 TI - The serological differentiation of mumps complement-fixation antigens. PMID- 20293215 TI - The localization of radiophosphate in cells. PMID- 20293216 TI - Studies on the pathogenesis of brucellosis. PMID- 20293217 TI - Thromboplastic action of plasma protease (tryptase). PMID- 20293218 TI - Chronic oral toxicity of alpha-naphthyl thiourea. PMID- 20293219 TI - Separation of two mutually antagonistic chromatophorotropins from the tritocerebral commissure of Crago. PMID- 20293220 TI - Radioautographs in which the tissue is mounted directly on the photographic plate. PMID- 20293221 TI - Storage, retention and distribution of folic acid in the chick. PMID- 20293222 TI - Intrasplenic transplantation of testes in castrated mice. PMID- 20293223 TI - Toxicity studies on rutin. PMID- 20293224 TI - Two antibiotics (lavendulin and actinorubin) produced by two strains of Actinomyces; toxicity and therapeutic studies. PMID- 20293225 TI - Production of increased capillary fragility in rats following irradiation. PMID- 20293226 TI - Effect of rutin on recovery time from radiation injury in rats. PMID- 20293227 TI - Effect of colchicine on resting cells in tissue cultures. PMID- 20293228 TI - Production of polycythemia in rabbits by anoxia and cobalt. PMID- 20293229 TI - Effect of streptomycin on growth of rickettsiae in eggs. PMID- 20293230 TI - Action of curare on temperature changes in the brain in combination with pentobarbital narcosis. PMID- 20293231 TI - Growth of chicks on purified and synthetic diets containing amino acids. PMID- 20293232 TI - Absence of lipotropic activity of methionine when pure amino acids were substituted for dietary protein. PMID- 20293233 TI - Implantation of riboflavin pellets in animals and man. PMID- 20293234 TI - Action of sodium salicylate on hyaluronidase. PMID- 20293235 TI - Recovery of herpes simplex virus from rabbit brain nine months after inoculation. PMID- 20293236 TI - Artifacts in gold shadowed electron micrographs due to electrons of high intensity. PMID- 20293237 TI - Hypersensitivity to egg white in the rat. PMID- 20293238 TI - Cholinesterase content of erythrocytes in normal and pathological states; content in normal humans. PMID- 20293239 TI - A simple effective regimen for preservation of the dog with a pancreatic fistula. PMID- 20293240 TI - Demonstration of antibodies in acquired hemolytic anemia with anti-human globulin serum. PMID- 20293241 TI - Role of adrenalin in recovery of inhibited conditioned reactions. PMID- 20293242 TI - Biological value of proteins determined with Tetrahymena geleii H. PMID- 20293243 TI - Treatment of paroxysmal auricular or nodal tachycardia with the vasopressor drug, neosynephrine. PMID- 20293244 TI - Dark-field observations on lymphocytes exposed to X-rays and other injurious agents. PMID- 20293246 TI - Newer developments in urology during the war years. PMID- 20293245 TI - Anaphylaxis in the dog. PMID- 20293247 TI - Gross structure of the subcutaneous layer and its mechanical uses for the skin. PMID- 20293248 TI - The scope of industrial dentistry. PMID- 20293249 TI - [Not Available]. PMID- 20293250 TI - [Not Available]. PMID- 20293251 TI - [Not Available]. PMID- 20293252 TI - [Not Available]. PMID- 20293253 TI - [Not Available]. PMID- 20293254 TI - [Not Available]. PMID- 20293255 TI - [Not Available]. PMID- 20293256 TI - [Not Available]. PMID- 20293257 TI - [Not Available]. PMID- 20293258 TI - [Not Available]. PMID- 20293259 TI - [Not Available]. PMID- 20293260 TI - [Not Available]. PMID- 20293261 TI - [Not Available]. PMID- 20293262 TI - [Not Available]. PMID- 20293263 TI - [Not Available]. PMID- 20293264 TI - [Not Available]. PMID- 20293265 TI - [Not Available]. PMID- 20293266 TI - [Not Available]. PMID- 20293267 TI - [Not Available]. PMID- 20293268 TI - [Not Available]. PMID- 20293269 TI - [Not Available]. PMID- 20293270 TI - [Not Available]. PMID- 20293271 TI - [Not Available]. PMID- 20293272 TI - [Not Available]. PMID- 20293273 TI - [Not Available]. PMID- 20293274 TI - [Not Available]. PMID- 20293275 TI - [Not Available]. PMID- 20293276 TI - [Not Available]. PMID- 20293277 TI - [Not Available]. PMID- 20293278 TI - Relief of pain. PMID- 20293279 TI - Modern anaesthetic practice. PMID- 20293280 TI - Analgesia and anaesthesia in obstetrics. PMID- 20293281 TI - Clinical experiences with nitrogen mustard in Hodgkin's disease. PMID- 20293282 TI - Sensory disturbances in chronic visceral disease. PMID- 20293283 TI - Some aspects of the future of medical practice. PMID- 20293284 TI - Sulfasuxidine and sulfathalidine in surgery of the colon. PMID- 20293285 TI - Translumbar aortography; an aid in the management of the hydronephrotic kidney. PMID- 20293286 TI - Vagal resection in the treatment of gastroduodenal ulcer. PMID- 20293287 TI - Diagnosis and treatment of cardiospasm. PMID- 20293288 TI - The treatment of fibrosarcoma. PMID- 20293289 TI - The first proctologist; the life and writings of Joseph McDowell Mathews. PMID- 20293290 TI - The comparative clinical values of some drugs in the pyodermas. PMID- 20293291 TI - Diagnoses commonly missed in general practice. PMID- 20293292 TI - The Mental Health Act and plans for its operation. PMID- 20293293 TI - The practical handling of bacteriology by the clinical pathologist. PMID- 20293294 TI - Retarding denervation atrophy. PMID- 20293295 TI - Irradiation therapy of benign uterine hemorrhage. PMID- 20293296 TI - Vascular mechanisms in allergic headaches. PMID- 20293297 TI - The value of the electrocardiogram in the diagnosis of early rheumatic heart disease. PMID- 20293299 TI - The good doctor. PMID- 20293298 TI - Metastatic malignancy of the brain and spinal cord; a clinico-pathologic study. PMID- 20293300 TI - Principles of treatment in fracture of the neck of the femur. PMID- 20293301 TI - Newer obstetric analgesics; compounds No. 10720 and No. 10820, dolophine. PMID- 20293302 TI - The present status of penicillin. PMID- 20293303 TI - Recent developments in the treatment of dental caries. PMID- 20293304 TI - Variability in tolerance to depressant drugs. PMID- 20293305 TI - Calcific pericarditis (with multiple pulmonary infarcts). PMID- 20293306 TI - Practical orientation in neurosyphilis. PMID- 20293307 TI - The value of penicillin in the treatment of postpneumonic empyema. PMID- 20293308 TI - Transfusion anuria and related processes. PMID- 20293309 TI - BAL therapy of dermatitis caused by injections of gold salts. PMID- 20293310 TI - Aneurysm of the splenic artery. PMID- 20293311 TI - The urinary 17-ketosteroids. PMID- 20293313 TI - The teaching of anatomy. PMID- 20293312 TI - CHEMICAL structure of antibiotics. PMID- 20293314 TI - The learning of anatomy. PMID- 20293315 TI - The mental effects of drugs. PMID- 20293316 TI - The comparative anatomy and physiology of the caecum, in reference to the occurrence of appendicitis in man. PMID- 20293317 TI - Industrial health. PMID- 20293318 TI - [Not Available]. PMID- 20293319 TI - [Not Available]. PMID- 20293320 TI - [Not Available]. PMID- 20293321 TI - [Not Available]. PMID- 20293322 TI - [Not Available]. PMID- 20293323 TI - [Not Available]. PMID- 20293324 TI - [Not Available]. PMID- 20293325 TI - [Not Available]. PMID- 20293326 TI - An anatomic study of the vagus nerves, and a technic of transabdominal gastric vagus resection. PMID- 20293327 TI - 1946 Aerobiologic survey for Ann Arbor, Michigan. PMID- 20293328 TI - The evaluation of thiouracil in hyperthyroidism. PMID- 20293329 TI - Treatment of acute bulbar poliomyelitis. PMID- 20293330 TI - Pediatric allergy. PMID- 20293331 TI - The management of uterine bleeding. PMID- 20293332 TI - [Not Available]. PMID- 20293333 TI - [Not Available]. PMID- 20293334 TI - [Not Available]. PMID- 20293335 TI - [Not Available]. PMID- 20293336 TI - [Not Available]. PMID- 20293337 TI - [Not Available]. PMID- 20293338 TI - [Not Available]. PMID- 20293339 TI - [Not Available]. PMID- 20293340 TI - [Not Available]. PMID- 20293341 TI - [Not Available]. PMID- 20293342 TI - [Not Available]. PMID- 20293343 TI - [Not Available]. PMID- 20293344 TI - [Not Available]. PMID- 20293345 TI - [Not Available]. PMID- 20293346 TI - [Not Available]. PMID- 20293347 TI - [Not Available]. PMID- 20293348 TI - [Not Available]. PMID- 20293349 TI - [Not Available]. PMID- 20293350 TI - [Not Available]. PMID- 20293352 TI - [Not Available]. PMID- 20293351 TI - [Not Available]. PMID- 20293353 TI - [Not Available]. PMID- 20293354 TI - [Not Available]. PMID- 20293355 TI - [Not Available]. PMID- 20293356 TI - [Not Available]. PMID- 20293357 TI - [Not Available]. PMID- 20293358 TI - [Not Available]. PMID- 20293359 TI - [Not Available]. PMID- 20293360 TI - [Not Available]. PMID- 20293361 TI - [Not Available]. PMID- 20293362 TI - [Not Available]. PMID- 20293363 TI - [Not Available]. PMID- 20293364 TI - [Not Available]. PMID- 20293365 TI - [Not Available]. PMID- 20293366 TI - [Not Available]. PMID- 20293367 TI - [Not Available]. PMID- 20293368 TI - [Not Available]. PMID- 20293369 TI - [Not Available]. PMID- 20293370 TI - [Not Available]. PMID- 20293371 TI - [Not Available]. PMID- 20293372 TI - [Not Available]. PMID- 20293374 TI - [Not Available]. PMID- 20293373 TI - [Not Available]. PMID- 20293375 TI - [Not Available]. PMID- 20293376 TI - [Not Available]. PMID- 20293377 TI - [Not Available]. PMID- 20293378 TI - [Not Available]. PMID- 20293379 TI - [Not Available]. PMID- 20293380 TI - [Not Available]. PMID- 20293381 TI - [Not Available]. PMID- 20293382 TI - [Not Available]. PMID- 20293383 TI - [Not Available]. PMID- 20293385 TI - [Not Available]. PMID- 20293384 TI - [Not Available]. PMID- 20293386 TI - [Not Available]. PMID- 20293387 TI - [Not Available]. PMID- 20293388 TI - [Not Available]. PMID- 20293389 TI - [Not Available]. PMID- 20293390 TI - [Not Available]. PMID- 20293391 TI - [Not Available]. PMID- 20293392 TI - [Not Available]. PMID- 20293393 TI - [Not Available]. PMID- 20293394 TI - [Not Available]. PMID- 20293395 TI - [Not Available]. PMID- 20293396 TI - [Not Available]. PMID- 20293397 TI - [Not Available]. PMID- 20293398 TI - [Not Available]. PMID- 20293399 TI - [Not Available]. PMID- 20293400 TI - [Not Available]. PMID- 20293401 TI - [Not Available]. PMID- 20293402 TI - [Not Available]. PMID- 20293403 TI - [Not Available]. PMID- 20293404 TI - [Not Available]. PMID- 20293405 TI - [Not Available]. PMID- 20293406 TI - [Not Available]. PMID- 20293407 TI - [Not Available]. PMID- 20293408 TI - [Not Available]. PMID- 20293409 TI - [Not Available]. PMID- 20293410 TI - [Not Available]. PMID- 20293411 TI - [Not Available]. PMID- 20293412 TI - [Not Available]. PMID- 20293413 TI - [Not Available]. PMID- 20293414 TI - [Not Available]. PMID- 20293415 TI - [Not Available]. PMID- 20293416 TI - [Not Available]. PMID- 20293417 TI - [Not Available]. PMID- 20293418 TI - [Not Available]. PMID- 20293419 TI - [Not Available]. PMID- 20293420 TI - [Not Available]. PMID- 20293421 TI - [Not Available]. PMID- 20293422 TI - [Not Available]. PMID- 20293423 TI - [Not Available]. PMID- 20293424 TI - [Not Available]. PMID- 20293425 TI - [Not Available]. PMID- 20293426 TI - [Not Available]. PMID- 20293427 TI - [Not Available]. PMID- 20293428 TI - [Not Available]. PMID- 20293429 TI - [Not Available]. PMID- 20293430 TI - [Not Available]. PMID- 20293431 TI - [Not Available]. PMID- 20293432 TI - [Not Available]. PMID- 20293433 TI - [Not Available]. PMID- 20293434 TI - [Not Available]. PMID- 20293435 TI - [Not Available]. PMID- 20293436 TI - [Not Available]. PMID- 20293437 TI - [Not Available]. PMID- 20293439 TI - [Not Available]. PMID- 20293438 TI - [Not Available]. PMID- 20293440 TI - [Not Available]. PMID- 20293441 TI - [Not Available]. PMID- 20293442 TI - [Not Available]. PMID- 20293443 TI - [Not Available]. PMID- 20293444 TI - [Not Available]. PMID- 20293445 TI - [Not Available]. PMID- 20293446 TI - [Not Available]. PMID- 20293447 TI - [Not Available]. PMID- 20293448 TI - [Not Available]. PMID- 20293449 TI - [Not Available]. PMID- 20293450 TI - [Not Available]. PMID- 20293451 TI - [Not Available]. PMID- 20293452 TI - [Not Available]. PMID- 20293453 TI - [Not Available]. PMID- 20293455 TI - [Not Available]. PMID- 20293454 TI - [Not Available]. PMID- 20293456 TI - [Not Available]. PMID- 20293457 TI - [Not Available]. PMID- 20293458 TI - [Not Available]. PMID- 20293459 TI - [Not Available]. PMID- 20293460 TI - [Not Available]. PMID- 20293461 TI - [Not Available]. PMID- 20293462 TI - [Not Available]. PMID- 20293463 TI - [Not Available]. PMID- 20293464 TI - [Not Available]. PMID- 20293465 TI - [Not Available]. PMID- 20293466 TI - [Not Available]. PMID- 20293467 TI - [Not Available]. PMID- 20293468 TI - [Not Available]. PMID- 20293469 TI - [Not Available]. PMID- 20293470 TI - [Not Available]. PMID- 20293471 TI - [Not Available]. PMID- 20293472 TI - [Not Available]. PMID- 20293473 TI - [Not Available]. PMID- 20293474 TI - [Not Available]. PMID- 20293475 TI - [Not Available]. PMID- 20293476 TI - [Not Available]. PMID- 20293477 TI - [Not Available]. PMID- 20293478 TI - [Not Available]. PMID- 20293479 TI - [Not Available]. PMID- 20293480 TI - Some points in the radiological diagnosis of diseases of the bones and joints. PMID- 20293481 TI - Fractures of the wrist and ankle. PMID- 20293482 TI - Amebic abscess of the liver. PMID- 20293483 TI - The physician and tuberculosis. PMID- 20293484 TI - The treatment of malaria. PMID- 20293485 TI - Oral and aerosol penicillin in infants. PMID- 20293486 TI - Smear technic for cancer cells. PMID- 20293487 TI - Preventive mental health and the physician. PMID- 20293488 TI - Carcinoma of the skin and lip. PMID- 20293489 TI - Functional urinary frequency in the soldier. PMID- 20293490 TI - Neuropsychiatric casualties in an infantry division. PMID- 20293491 TI - Treatment of plantar corns. PMID- 20293492 TI - Ventilation rates of sealed aircraft cabins. PMID- 20293493 TI - Coccidioidal meningitis. PMID- 20293494 TI - Poliomyelitis. PMID- 20293495 TI - A technique for hemorrhoidectomy. PMID- 20293496 TI - SUBLINGUAL dermoid cyst. PMID- 20293497 TI - Maintenance of femoral skeletal traction. PMID- 20293498 TI - MANDIBULAR graft retention by Kirschner wire. PMID- 20293499 TI - Management of psychotic patients in a general hospital overseas. PMID- 20293500 TI - An improvised microscope stage warmer. PMID- 20293501 TI - Use of splint in transferring tube skin grafts from forearm to lower leg. PMID- 20293502 TI - Hazor-blade knife for Padgett dermatome. PMID- 20293503 TI - A compression fracture of the spine. PMID- 20293504 TI - Femoral transfusion in shock. PMID- 20293505 TI - BOTULISM. PMID- 20293506 TI - The administration of fixed hospital laboratories. PMID- 20293507 TI - Acute relapsing gastro-enteritis. PMID- 20293509 TI - Gonnorrheal arthritis with keratodermia blennorrhagicum. PMID- 20293508 TI - A rapid cultural method for the presumptive identification of Clostridium welchii. PMID- 20293510 TI - Gun shot wound of heart with removal of bullet. PMID- 20293511 TI - Red Cross social service in a military hospital. PMID- 20293512 TI - Improvised ward equipment. PMID- 20293513 TI - Aerial spraying of DDT. PMID- 20293514 TI - Comments on orthodontia. PMID- 20293515 TI - Quality control of Danish milk supply. PMID- 20293516 TI - Special disease hazards in basic training centers. PMID- 20293517 TI - The determination of sulfate as barium sulfate; in the presence of metals of the acid hydrogen sulfide group. PMID- 20293518 TI - Early steam engines in America. PMID- 20293519 TI - The blood picture of normal laboratory animals; a review of the literature 1936 1946. PMID- 20293520 TI - The Amazonian varieties of Lonchocarpus nicou, a rotenone-yielding plant. PMID- 20293521 TI - New Guinea species of mosquitoes of the genus Aedes, subgenus Aedes. PMID- 20293522 TI - A new species of flea of the genus Opisodasys from Mexico. PMID- 20293523 TI - What chemistry owes to X-rays. PMID- 20293524 TI - Secretion of red blood corpuscles. PMID- 20293525 TI - Scrub typhus as a study in ecology. PMID- 20293526 TI - Electrogenic properties of acetylcholine. PMID- 20293527 TI - Metabolism of fatty livers. PMID- 20293528 TI - Artificial breaking of the diapause in Drosophila nitens. PMID- 20293529 TI - A continuum theory of rheological phenomena. PMID- 20293530 TI - The body's chemical mechanism of defence. PMID- 20293531 TI - Coumarin as a selective phytocidal agent. PMID- 20293532 TI - Determination of the energy and momentum of fast neutrons in cosmic rays. PMID- 20293533 TI - Detectability of the negative proton. PMID- 20293534 TI - Effect of sodium hexametaphosphate on the yield value and viscosity of a hydrogen bentonite suspension. PMID- 20293535 TI - Structure of the keratin molecule. PMID- 20293536 TI - Transference of vitamin D from the female rat to her young. PMID- 20293537 TI - Heat treatment and the biological value of soya-bean protein. PMID- 20293538 TI - Solvent-treated cellulose acetate as the stationary phase in partition chromatography. PMID- 20293539 TI - Atomic energy and its applications. PMID- 20293540 TI - Dr. James Hutton and the manufacture of sal ammoniac. PMID- 20293541 TI - NATURE of virulence. PMID- 20293542 TI - Use of punched card tabulating machines for crystallographic Fourier syntheses. PMID- 20293543 TI - Orientation of fibrils in natural membranes. PMID- 20293544 TI - A new method of studying the structure of alloys by magnetic analysis. PMID- 20293545 TI - Xanthine oxidase and virus growth. PMID- 20293546 TI - The premaxilla and the ancestry of man. PMID- 20293547 TI - A sensitive Cartesian diver balance. PMID- 20293548 TI - A haemosporidian of bats. PMID- 20293549 TI - Quantitative chromatographic separations of synthetic peptides. PMID- 20293550 TI - Growth of the physical sciences and their applications in the United States. PMID- 20293551 TI - Botanical sciences and their applications, including agriculture. PMID- 20293552 TI - Eighteenth century theories on America as a human habitat. PMID- 20293553 TI - Trends in American medical research during the nineteenth century. PMID- 20293554 TI - The freedom of science. PMID- 20293555 TI - Epidemic diseases. PMID- 20293556 TI - International problems in plant disease control. PMID- 20293557 TI - The role of the amino acids in human nutrition. PMID- 20293558 TI - Publication and the distribution of publications. PMID- 20293559 TI - The international scientific unions. PMID- 20293561 TI - The interchange of men of science. PMID- 20293560 TI - International scientific congresses. PMID- 20293562 TI - The United Nations Educational, Scientific and Cultural Organization. PMID- 20293564 TI - The effect of various condensing agents and inert solvents in the production of DDT. PMID- 20293565 TI - Group interpretation of test results. PMID- 20293566 TI - Practical problems of military psychology in war and peace. PMID- 20293567 TI - The application of anthropological techniques to cross-national communication. PMID- 20293568 TI - Humanities in the broadest sense. PMID- 20293569 TI - COMMITTEE on Coordination of Cosmic-Ray Investigations; progress report for the period July 1945 to June 1946. PMID- 20293570 TI - Statistical investigation of cosmic-ray variations at Department of Terrestrial Magnetism. PMID- 20293571 TI - Cosmic-ray investigations at New York University. PMID- 20293572 TI - Antibacterial properties of fatty acids. PMID- 20293574 TI - Paleobotany. PMID- 20293575 TI - The effect of androgens upon the embryonic urinogenital system. PMID- 20293573 TI - Plant pigments. PMID- 20293576 TI - The gene. PMID- 20293577 TI - Genetic structure of natural populations. PMID- 20293578 TI - Mouse leukemia. PMID- 20293579 TI - Maize genetics. PMID- 20293580 TI - Cotton genetics. PMID- 20293581 TI - Division of Historical Research. PMID- 20293582 TI - Social anthropological research. PMID- 20293583 TI - Extracortical connections of the primate frontal cerebral cortex; corticifugal connections. PMID- 20293584 TI - Heterotopic neurons of sensory type in the intramedullary portion of the motor roots. PMID- 20293585 TI - Chemical sense and taste in the fishes, Prionotus and Trichogaster. PMID- 20293586 TI - A study of the factors controlling the differentiation of Mauthner's cell in Amblystoma. PMID- 20293587 TI - Depletions in the thoraco-lumbar sympathetic system following removal of neural crest in the chick. PMID- 20293588 TI - Chronic progressive ophthalmoplegia of myopathic origin. PMID- 20293589 TI - Paget's disease of atlas and axis. PMID- 20293590 TI - Effects of vitamin and hormone treatment on senile patients. PMID- 20293591 TI - Nerve biopsy. PMID- 20293592 TI - The pattern of olfactory innervation. PMID- 20293593 TI - Deposition of iron in paraventricular areas of the human brain in hemochromatosis. PMID- 20293594 TI - Neurogliogenic tumor of the diencephalon with unusual characteristics; report on a case with discussion of classification. PMID- 20293595 TI - Neoplastic transformation of the subependymal cell plate in the floor of the fourth ventricle (subependymal spongioblastoma) with a clinicopathologic case report. PMID- 20293596 TI - Parenchymatous cortical cerebellar atrophy associated with Pick's disease. PMID- 20293597 TI - The relation of the spinal subarachnoid and perineurial spaces. PMID- 20293598 TI - The cerebrospinal fluid pathways (a critical note). PMID- 20293599 TI - On the mechanism and localization of the symptoms of electroshock and electronarcosis. PMID- 20293600 TI - Temporal lobotomy. PMID- 20293601 TI - Extirpation of the cortical arm area as defined by stimulation under conditions of primary facilitation (Macaca mulatta). PMID- 20293602 TI - Convulsant effects of penicillin on the cerebral cortex. PMID- 20293603 TI - Experimental non-suppurative pneumonia encephalitis produced by injection of homologous lung extract. PMID- 20293604 TI - Bilateral destruction of the prefrontal areas and subsequent thalamic changes; report of a case. PMID- 20293605 TI - The meningeal reaction in brain abscess. PMID- 20293606 TI - Schizencephalies; congenital symmetrical clefts in the cerebral mantle associated with extensive defect in the roof plate (encephalocele and meningomyelocele). PMID- 20293607 TI - Further uses of gelatin foam in neurosorgery. PMID- 20293608 TI - Resection of the greater superficial petrosal nerve in the treatment of unilateral headache. PMID- 20293609 TI - Dermatome hypalgesia with posterolateral herniation of lower cervical intervertebral disc. PMID- 20293610 TI - Evidence of active invasion of denervated areas by sensory fibers from neighboring nerves in man. PMID- 20293611 TI - Peripheral nerve injuries; basic data from the peripheral nerve registry concerning 7,050 nerve sutures and 67 nerve grafts. PMID- 20293612 TI - Experimental hydrocephalus. PMID- 20293613 TI - Cerebrospinal rhinorrhea by way of the eustachian tube; report of cases with the dural defects in the middle or posterior fossa. PMID- 20293614 TI - Trigeminal neuralgia due to contralateral tumors of the posterior cranial fossa; report of 2 cases. PMID- 20293615 TI - Resection of the superior longitudinal sinus; report of case. PMID- 20293616 TI - Autodermography; a new and simple method of demonstrating the propagation of pain and disorders of surface sensibility. PMID- 20293617 TI - Psychoanalytic insight into insomnia. PMID- 20293618 TI - The symbolism of the symbol. PMID- 20293619 TI - Psychosomatic aspects of obesity. PMID- 20293620 TI - Translator's prologue to Dreaming like waking [transl. by A. A. Brill]. PMID- 20293621 TI - Passive parasitic psychopathy: toward the personality structure and psychogenesis of idiopathic psychopathy (anethopathy). PMID- 20293622 TI - Comments on the formation of psychic structure. PMID- 20293623 TI - The child's laughter; theoretical and clinical notes on the function of the comic. PMID- 20293624 TI - Twins; observations on environmental influences on their development. PMID- 20293625 TI - The pre-oedipal phase in the development of the male child. PMID- 20293626 TI - The child's ego development and the training of adults in his environment. PMID- 20293627 TI - Hospitalism; a follow-up report. PMID- 20293628 TI - The psychoanalytic study of infantile feeding disturbances. PMID- 20293629 TI - The psychogenic tic in ego development. PMID- 20293630 TI - Psychoanalytic contributions to the problems of reading disabilities. PMID- 20293631 TI - The analysis of a case of night terror. PMID- 20293632 TI - Hysterical twilight states in an eight-year-old child. PMID- 20293633 TI - Experiences with enuretics. PMID- 20293634 TI - A case of superego disintegration. PMID- 20293635 TI - Headline intelligence. PMID- 20293636 TI - A contribution to the problem of psychoses in childhood. PMID- 20293637 TI - Diaries of adolescent schizophrenics (hebephrenics). PMID- 20293638 TI - Anaclitic depression; an inquiry into the genesis of psychiatric conditions in early childhood. PMID- 20293640 TI - Ego development and historical change; clinical notes. PMID- 20293639 TI - Psychoanalytic oreintation in child guidance work in Great Britain. PMID- 20293641 TI - Incentives to development and means of early education. PMID- 20293642 TI - Psychological invalidism in thyroidectomized patients. PMID- 20293643 TI - Psychosomatic medicine; somatization reactions. PMID- 20293644 TI - Brief psychotherapy in psychosomatic problems. PMID- 20293645 TI - Ill health as an expression of anxiety in a combat unit. PMID- 20293646 TI - Central angiospastic retinopathy; a psychosomatic study of its occurrence in military personnel. PMID- 20293647 TI - The phantom limb. PMID- 20293648 TI - Psychosomatic medicine in an Army hospital in India. PMID- 20293649 TI - Emotional factors in urticaria; a report of three cases. PMID- 20293650 TI - A case of co-existence of idiopathic epileptic and psychogenic convulsions. PMID- 20293651 TI - Psychosurgery; the nursing problem. PMID- 20293652 TI - The pediatric nurse and human relations. PMID- 20293653 TI - Nursing in New Zealand. PMID- 20293654 TI - Care of the skin in older people. PMID- 20293655 TI - Office nursing. PMID- 20293656 TI - Precautions in working with radium. PMID- 20293657 TI - Head nurses look at nursing. PMID- 20293658 TI - Eye hygiene. PMID- 20293659 TI - Role of the nurse in rehabilitation. PMID- 20293660 TI - PROVIDING eye care in industry. PMID- 20293661 TI - Recent emphases in educational practices. PMID- 20293662 TI - EDUCATIONAL qualifications of first-year students in 1946. PMID- 20293663 TI - Eye care. PMID- 20293664 TI - Nutrition education and the public health nurse. PMID- 20293665 TI - Public health nursing in Prince Edward Island. PMID- 20293666 TI - Nursing care study of Boeck's sarcoid. PMID- 20293667 TI - Bernardini Ramazzini, his life, deeds and book. PMID- 20293668 TI - What does management expect in the plant medical program. PMID- 20293669 TI - Medical departments or first aid kits. PMID- 20293670 TI - The forward march of industrial nursing in West Virginia. PMID- 20293671 TI - Posture fundamentals in nursing. PMID- 20293672 TI - UNNRRA nursing; an international experience. PMID- 20293673 TI - Preparation of the mental hygiene nurse consultant: progress report of the work of the Committee on Mental Hygiene. PMID- 20293675 TI - Child development and the school nurse. PMID- 20293674 TI - Progress in education as it concerns industrial nursing. PMID- 20293676 TI - NURSE in the school health program; report of the Committee on Qualifications of the Nurse in the School. PMID- 20293677 TI - Role of the school nurse in safety education. PMID- 20293678 TI - Posture and the school health program. PMID- 20293679 TI - [Not Available]. PMID- 20293680 TI - [Not Available]. PMID- 20293682 TI - [Not Available]. PMID- 20293681 TI - [Not Available]. PMID- 20293683 TI - Disease processes versus disease pictures in interpretation of retinal vascular lesions. PMID- 20293684 TI - Aims and aids in the teaching of basic sciences in ophtalmology. PMID- 20293685 TI - Primary lipid dystrophy of the cornea. PMID- 20293686 TI - Esotropia following occlusion. PMID- 20293687 TI - Pentothal sodium in ophthalmic surgery. PMID- 20293688 TI - Optokinetic and other factors modifying vestibular nystagmus. PMID- 20293689 TI - Changes in retinal arterioles associated with the hypertensions of pregnancy. PMID- 20293690 TI - Ophthalmoscopic changes associated with hypertensive vascular disease as a guide to sympathectomy. PMID- 20293691 TI - Keratoconjunctivitis due to a diphtheroid-like organism; report of a case. PMID- 20293692 TI - Sensorial retinal relationship in concomitant strabismus. PMID- 20293693 TI - Experimental observations on the intravitreous use of penicillin and other drugs. PMID- 20293694 TI - A case of the Laurence-Moon-Beidl syndrome showing atypical retinitis pigmentosa associated with macular dystrophy. PMID- 20293697 TI - Summary of the work on the pathological changes in the aqueous-humour and the blood-aqueous barrier, at Zurich. PMID- 20293700 TI - Circulatory studies of the fundus of the eye. PMID- 20293698 TI - A Gronblad-Strandberg syndrome. PMID- 20293701 TI - Removal of the wrong eye. PMID- 20293702 TI - Indications and contraindications for extracapsular and intracapsular extraction of cataract. PMID- 20293703 TI - Headaches of ocular origin. PMID- 20293704 TI - Orbital cellulitis secondary to maxillary sinusitis; report of a case. PMID- 20293705 TI - Tinnitus aurium; including report of results following Lempert fenestration and tympanosympathectomy. PMID- 20293706 TI - Strand formations in the anterior chamber. PMID- 20293708 TI - The screen test (cover test). PMID- 20293707 TI - Plastic repair of cartilaginous nasal defects; a new donor site. PMID- 20293709 TI - Amblyopia cum polyneuropathia caused by starvation. PMID- 20293710 TI - [Not Available]. PMID- 20293711 TI - [Not Available]. PMID- 20293712 TI - [Not Available]. PMID- 20293713 TI - [Not Available]. PMID- 20293714 TI - [Not Available]. PMID- 20293715 TI - Potassiumiodide and vitreous opacities. PMID- 20293716 TI - Review of contributions of World War II to ophthalmology. PMID- 20293717 TI - [Not Available]. PMID- 20293718 TI - [Not Available]. PMID- 20293719 TI - [Not Available]. PMID- 20293720 TI - [Not Available]. PMID- 20293721 TI - [Not Available]. PMID- 20293722 TI - [Not Available]. PMID- 20293723 TI - [Not Available]. PMID- 20293724 TI - Camp Amblyopia. PMID- 20293725 TI - [Not Available]. PMID- 20293726 TI - A review of the available literature on the larynx and laryngeal surgery for 1946. PMID- 20293727 TI - Studies on oral penicillin. PMID- 20293728 TI - Changes in the color of the pharynx following smoking. PMID- 20293729 TI - The trend of treatment of bronchiectasis during the past two decades. PMID- 20293730 TI - An introducer for tracheostomy tubes. PMID- 20293731 TI - A modification of the Negus esophagoscope. PMID- 20293732 TI - The immunological relationships of strains of contagious pustular dermatitis virus. PMID- 20293733 TI - The relationship between the virus of contagious pustular dermatitis and a virus isolated from sheep papillomatosis by Selbie. PMID- 20293734 TI - The prophylactic use of phenanthridinium 1553 against infection with T. congolense and T. vivax. PMID- 20293735 TI - Studies on Corynebacterium renale; penicillin treatment of experimentally infected mice. PMID- 20293736 TI - The ascorbic acid content of the blood serum of farm animals. PMID- 20293737 TI - Sex hormones in the urine of pregnant cattle. PMID- 20293738 TI - A Salmonella strain isolated from camels in Palestine. PMID- 20293739 TI - Trace element deficiency in livestock in the Hebrides. PMID- 20293740 TI - Leptospirosis in cattle in Palestine. PMID- 20293741 TI - Ornithosis (psittacosis) in a pigeon flock. PMID- 20293742 TI - Salmonella typhi murium in penguins. PMID- 20293743 TI - [Not Available]. PMID- 20293744 TI - [Not Available]. PMID- 20293745 TI - [Not Available]. PMID- 20293746 TI - [Not Available]. PMID- 20293747 TI - Postacidotic state of infantile diarrhea: symptoms and chemical data; postacidotic hypocalcemia and associated decreases in levels of potassium, phosphorus and phosphatase in the plasma. PMID- 20293748 TI - Feeding of premature infants; a comparison of human and cow's milk. PMID- 20293749 TI - Erythema infectiosum. PMID- 20293750 TI - Juvenile osteopetrosis; metabolic studies in two cases and further observations on the composition of the bones in this disease. PMID- 20293751 TI - Hypervitaminosis A. PMID- 20293752 TI - Agenesis of the lung; with a review of the literature. PMID- 20293753 TI - Effect on the organisms of children of privations caused by the siege of Budapest. PMID- 20293754 TI - Prophylaxis of upper respiratory infections in children by oral penicillin and influenza virus vaccine inoculation. PMID- 20293755 TI - Analogous reactions of the poliomyelitis virus and cyanogen compounds. PMID- 20293756 TI - Fevers in children; their significance, general diagnostic value and antipyretic treatment. PMID- 20293757 TI - Pneumococcic meningitis. PMID- 20293758 TI - Scarlet fever (convalescent); acute rheumatic fever. PMID- 20293759 TI - Bronchopneumonia, pulmonary edema, rheumatic mitral and aortic heart disease. PMID- 20293761 TI - The relative activity of prostigmine homologues and other substances as antagonists to tubocurarine. PMID- 20293767 TI - The nutritive aspects of the amino acids. PMID- 20293768 TI - History of protein chemistry. PMID- 20293770 TI - A review of the biological assay of gelsemium. PMID- 20293769 TI - Protein hydrolyzates. PMID- 20293771 TI - A review of the biological assay of Veratrum viride. PMID- 20293772 TI - MYANESIN; a new muscle-relaxing agent. PMID- 20293773 TI - Food poisoning. PMID- 20293774 TI - The tragedy of the chronic sick. PMID- 20293775 TI - Dysmenorrhoea. PMID- 20293776 TI - Penicillin dispensing, from a new angle. PMID- 20293777 TI - PRACTICAL chemistry competitions. PMID- 20293778 TI - Japanese pharmacy. PMID- 20293779 TI - T.S.A. License number 110 [penicillin production in a small pharmacy]. PMID- 20293780 TI - A survey of the pharmaceutical industry in the British Zone of Germany. PMID- 20293781 TI - Parenteral penicillin apparatus. PMID- 20293782 TI - The pharmaceutical department of the Zurich Canton Hospital. PMID- 20293783 TI - Stored blood and plasma. PMID- 20293785 TI - The treatment of varicose veins. PMID- 20293784 TI - The early diagnosis of cancer. PMID- 20293786 TI - Penicillin ointment. PMID- 20293787 TI - PHARMACISTS of Arnhem; how they met battle and evacuation. PMID- 20293788 TI - Action of mustard gas and other poisons on yeast cells; study of the effects of divinyl sulfone and their reversal. PMID- 20293789 TI - Counter-emfs in the onion root. PMID- 20293790 TI - Potential oscillations in the onion root resulting from current flow. PMID- 20293791 TI - The dissociation of carbohydrate assimilation from catabolism. PMID- 20293792 TI - Cellular mechanisms controlling rates of glucose consumption by yeast. PMID- 20293793 TI - The effect of prolonged starvation on the lipids in Phascolosoma gouldii. PMID- 20293794 TI - The convulsive effect of penicillin on an amphibian nervous system. PMID- 20293795 TI - On the nature of pain. PMID- 20293796 TI - Heat: man's exchanges and physiological responses. PMID- 20293798 TI - A review of physiological and psychological studies of sexual behavior in mammals. PMID- 20293799 TI - Recent advances in the study of biological competition between structurally related compounds. PMID- 20293797 TI - The definition and meaning of pH. PMID- 20293800 TI - Plumage sequence in a case of hemilateral asymmetry in male hybrid fowl. PMID- 20293801 TI - The relation of the plumage-tract gradients to the serial localization of feather pigments in a hybrid cock. PMID- 20293802 TI - Phosphorylation in the frog's egg. PMID- 20293803 TI - Riboflavin and other fluorescent compounds in a developing egg (Orthoptera). PMID- 20293804 TI - The effects of thiourea on the oxygen consumption of Fundulus. PMID- 20293805 TI - The effect of salts and osmotic concentration on the size of food vacuoles in Vorticella similis. PMID- 20293806 TI - An analysis of photoelectric instruments for measurement of turbidity with reference to serology. PMID- 20293807 TI - The influence of the sinus glands upon molting and associated changes in the crayfish. PMID- 20293808 TI - An analysis of action on science legislation in the last Congress. PMID- 20293809 TI - The foreign language requirement for the Ph.D. PMID- 20293810 TI - Psychology and psychiatry. PMID- 20293811 TI - VALIDATION of the general clerical abilities test for selection and placement of War Department civilian personnel. PMID- 20293812 TI - Some areas of caution for the psychology student. PMID- 20293813 TI - Function of the Disciplinary Barracks' psychologist in the development of a therapeutic atmosphere. PMID- 20293814 TI - The clinical psychologist as correctional classification officer. PMID- 20293815 TI - The clinical psychologist assigned to a disciplinary barracks hospital. PMID- 20293816 TI - The psychologist in the employment office of a disciplinary barracks. PMID- 20293817 TI - Some notes on research on personality testing. PMID- 20293818 TI - The duties performed by clinical psychologists in Army medical installations. PMID- 20293819 TI - Clinical psychology 1896-1946. PMID- 20293821 TI - Psychometric pitfalls in clinical practice. PMID- 20293820 TI - Clinical psychology and psychiatry. PMID- 20293822 TI - An experimental study of intellectual control under stress and associated Rorschach factors. PMID- 20293823 TI - A preliminary report of the psychosocial effects of poliomyelitis. PMID- 20293824 TI - A comparison of one unsuccessful with four successful nondirectively counseled cases. PMID- 20293825 TI - The incomplete sentences test as a method of studying personality. PMID- 20293826 TI - The use of psychometric instruments in psychological clinics. PMID- 20293827 TI - Correlates of criminal behavior. PMID- 20293828 TI - Abilities and interests of Japanese-American high school seniors. PMID- 20293829 TI - Frame of reference in pro and anti evaluations of test items. PMID- 20293830 TI - A descriptive portrait of the drinker; the normal drinker. PMID- 20293831 TI - A descriptive portrait of the drinker; the symptomatic drinker. PMID- 20293832 TI - A descriptive portrait of the drinker; the psychotic drinker. PMID- 20293833 TI - A descriptive portrait of the drinker; the stupid drinker. PMID- 20293834 TI - The psychological effects of unionism on the member. PMID- 20293835 TI - Psychological tests in the Royal Navy, Army and A. T. S. PMID- 20293836 TI - Some problems of discipline among adolescents in factories. PMID- 20293837 TI - The development of personnel selection procedure in a naval entry establishment. PMID- 20293838 TI - A study of some stresses and strains within the working group. PMID- 20293839 TI - Perceptual abstraction and art. PMID- 20293840 TI - A theoretical derivation of latent learning. PMID- 20293841 TI - Consciousness as organismic physiological functioning. PMID- 20293842 TI - Test reliability; its meaning and determination. PMID- 20293843 TI - Table for determining phi coefficients. PMID- 20293844 TI - The use of psychological techniques in measuring and critically analyzing navigators' flight performance. PMID- 20293845 TI - Analysis in terms of frequencies of differences. PMID- 20293846 TI - An index of item validity providing a correction for chance success. PMID- 20293847 TI - A Rorschach study of operational fatigue in Army Air Forces combat personnel. PMID- 20293848 TI - Content analysis in Rorschach work. PMID- 20293849 TI - The Rorschach method in psychosomatic problems; a case of hypertensive cardiovascular disease. PMID- 20293850 TI - Human whole and detail responses in the Rorschach test. PMID- 20293851 TI - Personality patterns of old age. PMID- 20293852 TI - Tenth report on data of anti-rabies treatments supplied by Pasteur institutes. PMID- 20293853 TI - The biological assay and control of tetanus toxoid. PMID- 20293854 TI - On the standardisation of Haffkine Institute polyvalent anti-snake-venom serum against the venoms of the four common Indian snakes (cobra, common krait, Russell's viper and sawscaled viper). PMID- 20293857 TI - Nutrition in rural districts in Greece. PMID- 20293855 TI - A provisional standard for staphylococcus B antitoxin. PMID- 20293856 TI - The ecology of sandflies at the larval stage and the epidemiology of the diseases transmitted by them. PMID- 20293858 TI - Evaluation of the fundamentals of motor performance. PMID- 20293859 TI - Improving the quality of school medical services. PMID- 20293860 TI - The osteopathic treatment for lobar pneumonia. PMID- 20293861 TI - Primary atypical pneumonia of unknown etiology. PMID- 20293862 TI - The role of a successfully operated tumor clinic in a cancer control program; a discussion of responsibilities in the operation of such a clinic. PMID- 20293863 TI - Nephrosclerosis, benign and malignant. PMID- 20293864 TI - Cyanosis in the newborn. PMID- 20293865 TI - Reflexes. PMID- 20293866 TI - Refrigeration anesthesia. PMID- 20293867 TI - Methods adopted in the detection of the carrier. PMID- 20293868 TI - The history of state medicine in England; from the accession of Queen Victoria to the General Board of Health. PMID- 20293869 TI - RECORD low mortality in 1946. PMID- 20293870 TI - AGE at death in World War II. PMID- 20293872 TI - DIVORCE increasing rapidly in Canada. PMID- 20293871 TI - APPENDICITIS mortality near vanishing point. PMID- 20293873 TI - RECENT gains in cancer control. PMID- 20293874 TI - LOW mortality among wounded in World War II. PMID- 20293875 TI - AMERICANS marry young. PMID- 20293876 TI - CATASTROPHIC accidents, a ten-year survey. PMID- 20293877 TI - DEATH and the Negro. PMID- 20293879 TI - [Not Available]. PMID- 20293878 TI - AGES of United States Senators. PMID- 20293880 TI - [Not Available]. PMID- 20293881 TI - [Not Available]. PMID- 20293882 TI - [Not Available]. PMID- 20293883 TI - Some experiences with bone tumours. PMID- 20293884 TI - Symposium; industrial skin cancer with special reference to pitch and tar cancer. PMID- 20293885 TI - Standardised radiological pelvimetry; a new method of measuring the outlet. PMID- 20293886 TI - The physical properties of super-voltage x-rays. PMID- 20293887 TI - Guide to positioning. PMID- 20293888 TI - True lateral positioning of lumbar spine and pelvis. PMID- 20293890 TI - Laminagraphy; some technical and practical aspects. PMID- 20293889 TI - Radiography of mental patients. PMID- 20293891 TI - Problems of mass chest X-ray in industry. PMID- 20293892 TI - An evaluation of an automatic developing machine. PMID- 20293893 TI - From G. I. to R. T., training and opportunities. PMID- 20293894 TI - Radiography of the abdomen in suspected ruptured peptic ulcer. PMID- 20293895 TI - Technique for X-ray examination of nasal bones. PMID- 20293896 TI - PLASTER cast failures and safeguards. PMID- 20293897 TI - The vacuum-suction above knee leg. PMID- 20293898 TI - A rational approach to the surgery of high gastric ulcer. PMID- 20293899 TI - Bleeding as a late sequel of subtotal gastrectomy of the Billroth II type for duodenal ulcer. PMID- 20293900 TI - Supradiaphragmatic vagotomy in gastrojejunal ulceration following subtotal gastrectomy for duodenal ulcer. PMID- 20293901 TI - The significance of the gastric acidity in the surgical therapy of peptic ulcer. PMID- 20293902 TI - Anesthesia for gastric surgery. PMID- 20293903 TI - Are gastric ulcer and duodenal ulcer different diseases? PMID- 20293904 TI - The roentgen differentiation of benign and malignant ulcers. PMID- 20293905 TI - Malignant degeneration of chronic benign gastric ulcer. PMID- 20293906 TI - Coexisting ulcer and cancer of the stomach. PMID- 20293907 TI - Peptic ulcer as a psychosomatic disease. PMID- 20293908 TI - Gastrojejunocolic fistula. PMID- 20293909 TI - Proximal extension and progression following operations for regional ileitis. PMID- 20293910 TI - Mucocele and myxoglobulosis of the appendix. PMID- 20293911 TI - Early postoperative motor response of the small intestine to jejunal feedings. PMID- 20293912 TI - Nontumid ileocolic intussusception in an adult; report of a case with cecal ulcer. PMID- 20293913 TI - Intussuscepting submucous lipoma of right colon. PMID- 20293914 TI - Salmonella typhi murium cholangitis treated with streptomycin. PMID- 20293915 TI - Spontaneous rupture of the common bile duct following choledocholithotomy. PMID- 20293916 TI - A rare anomaly of the cystic duct. PMID- 20293917 TI - Modified cholecystectomy in fulminating cholecystitis. PMID- 20293918 TI - Radical operations on the head of the pancreas. PMID- 20293919 TI - Factors influencing the management of pancreatic cysts. PMID- 20293920 TI - The surgical correction of congenital cleft lip. PMID- 20293921 TI - The surgical treatment of large hemangiomas of the face in children. PMID- 20293922 TI - Gross intestinal hemorrhage in infants and children. PMID- 20293923 TI - Hernia in childhood. PMID- 20293924 TI - Prevention of fetal wastage. PMID- 20293925 TI - The management of pregnancy and tuberculosis. PMID- 20293926 TI - Combined intrauterine and extrauterine pregnancy. PMID- 20293927 TI - Carcinoma of the female breast. PMID- 20293928 TI - Acute cholecystitis. PMID- 20293929 TI - Idiopathic ulcerative colitis. PMID- 20293930 TI - [Not Available]. PMID- 20293931 TI - [Not Available]. PMID- 20293932 TI - [Not Available]. PMID- 20293933 TI - [Not Available]. PMID- 20293934 TI - [Not Available]. PMID- 20293935 TI - [Not Available]. PMID- 20293936 TI - [Not Available]. PMID- 20293937 TI - [Not Available]. PMID- 20293939 TI - [Not Available]. PMID- 20293938 TI - [Not Available]. PMID- 20293940 TI - [Not Available]. PMID- 20293941 TI - [Not Available]. PMID- 20293942 TI - [Not Available]. PMID- 20293943 TI - [Not Available]. PMID- 20293944 TI - [Not Available]. PMID- 20293945 TI - [Not Available]. PMID- 20293946 TI - [Not Available]. PMID- 20293947 TI - [Not Available]. PMID- 20293948 TI - [Not Available]. PMID- 20293949 TI - [Not Available]. PMID- 20293950 TI - [Not Available]. PMID- 20293951 TI - Kwashiorkor (malignant malnutrition) arising in Assam. PMID- 20293952 TI - Tuberculous pericarditis in the African. PMID- 20293953 TI - Tropical pyomyositis. PMID- 20293954 TI - Chang shan in the treatment of malaria. PMID- 20293955 TI - The diagnosis of kala azar. PMID- 20293956 TI - Amoebiasis with special reference to treatment. PMID- 20293957 TI - Tropical ulcer. PMID- 20293958 TI - Survival of transfused red cells in blackwater fever circulation and of blackwater red cells in normal circulation (preliminary report). PMID- 20293959 TI - Clinical filariasis due to Acanthocheilonema (Filaria) perstans. PMID- 20293960 TI - Dividing forms of Plasmodium falciparum in the peripheral blood of Africans. PMID- 20293961 TI - Massive dose tryparsamide by intravenous drip method in the treatment of trypanosomiasis. PMID- 20293962 TI - Spray killing of mosquitoes. PMID- 20293963 TI - Treatment of bilharziasis with stilbamidine. PMID- 20293964 TI - A case of blackwater fever in an African girl. PMID- 20293965 TI - Chemotherapeutic suppression and prophylaxis in malaria. PMID- 20293966 TI - The use of the new insecticide DDT in relation to the problems of tropical medicine. PMID- 20293967 TI - The Manson saga, October 3, 1844-April 9, 1922. PMID- 20293968 TI - Further progress in the control of sleeping sickness in Nigeria. PMID- 20293969 TI - Variola minor in Kenya. PMID- 20293970 TI - Foot yaws. PMID- 20293971 TI - Anavenoms and their use in the preparation of antivenomous sera; polyvalent anti Bitis arietans-Naia flava serum and specific antivenenes against African viperine and colubrine venoms. PMID- 20293972 TI - Studies in leishmaniasis in the Anglo-Egyptian Sudan; espundia in a monkey infected experimentally with Sudan kala-azar. PMID- 20293973 TI - An investigation into the number of sporozoites found in the salivary glands of Anopheles mosquitoes. PMID- 20293974 TI - The anopheline mosquitoes of Melanesia. PMID- 20293975 TI - A case of rhinosporidiosis in an Indian male, aged 28. PMID- 20293976 TI - Field methods for estimating mepacrine in urine, blood and plasma. PMID- 20293977 TI - Recent research on kala-azar in India. PMID- 20293979 TI - The Meridi outbreak of sleeping sickness. PMID- 20293978 TI - Tsetse fly control and sleeping sickness in the Sudan. PMID- 20293980 TI - Vincent's infection in northern Peru. PMID- 20293981 TI - Spinal anaesthesia in the treatment of tropical ulcers. PMID- 20293982 TI - A staining method for malaria parasites in thick blood-films. PMID- 20293984 TI - Leprosy of the large intestine and gall-bladder; case report with review of the literature. PMID- 20293983 TI - Late results of treatment of sleeping sickness in Sierra Leone by antrypol tryparsamide pentamidine and propamidine singly and in various combinations. PMID- 20293985 TI - The chemotherapy of experimental leishmaniasis; a dose response curve for the activity of sodium stibogluconate. PMID- 20293986 TI - An investigation on new repellents for the protection of man against mosquito attacks. PMID- 20293987 TI - The identity of the ciliate Balantidium minutum, an alleged parasite of man. PMID- 20293988 TI - Observations on the coprophilic habits of a ciliate Balantiophorus minutus Schewiakoff. PMID- 20293990 TI - Amoebiasis. PMID- 20293989 TI - Types of Eberthella typhosa in Palestine. PMID- 20293991 TI - Tropical medicine in war and peace. PMID- 20293992 TI - Investigation into the efficacy of sulphadiazine in the treatment of malaria. PMID- 20293993 TI - Anaemia associated with the sickle cell trait in British West African natives. PMID- 20293994 TI - Studies on the Weltmann reaction in malaria cases. PMID- 20293995 TI - A contribution to the study of malnutrition in Central Africa; a syndrome of malignant malnutrition. PMID- 20293996 TI - Growth of Protozoa in tissue culture; Plasmodium gallinaceum, exoerythrocytic forms. PMID- 20293997 TI - A rapid method for detecting the sickle cell trait. PMID- 20293998 TI - Pulmonary resection in the treatment of pulmonary tuberculosis; analysis of 88 patients followed for a period of two to twelve years after operation. PMID- 20293999 TI - Oleothorax. PMID- 20294000 TI - BCG vaccination in Scandinavia; 20 years of uninterrupted vaccination against tuberculosis. PMID- 20294001 TI - The control of tuberculosis in Brazil; new orientation, a new mentality. PMID- 20294002 TI - Intravenous infection of the chick embryo with tubercle bacilli; inhibitory effects of streptomycin. PMID- 20294004 TI - Some facts concerning the physiology of respiration of interest to the tuberculosis patient. PMID- 20294003 TI - Effect of streptomycin on the tubercle bacillus; the use of Dubos' and other media in tests for streptomycin sensitivity. PMID- 20294005 TI - [Not Available]. PMID- 20294006 TI - [Not Available]. PMID- 20294007 TI - [Not Available]. PMID- 20294008 TI - [Not Available]. PMID- 20294009 TI - [Not Available]. PMID- 20294010 TI - [Not Available]. PMID- 20294011 TI - [Not Available]. PMID- 20294012 TI - [Not Available]. PMID- 20294013 TI - [Not Available]. PMID- 20294014 TI - [Not Available]. PMID- 20294015 TI - [Not Available]. PMID- 20294016 TI - [Not Available]. PMID- 20294017 TI - [Not Available]. PMID- 20294019 TI - [Not Available]. PMID- 20294018 TI - [Not Available]. PMID- 20294020 TI - [Not Available]. PMID- 20294021 TI - [Not Available]. PMID- 20294022 TI - [Not Available]. PMID- 20294023 TI - [Not Available]. PMID- 20294024 TI - [Not Available]. PMID- 20294025 TI - [Not Available]. PMID- 20294026 TI - [Not Available]. PMID- 20294027 TI - [Not Available]. PMID- 20294028 TI - [Not Available]. PMID- 20294029 TI - [Not Available]. PMID- 20294030 TI - [Not Available]. PMID- 20294031 TI - [Not Available]. PMID- 20294032 TI - [Not Available]. PMID- 20294033 TI - [Not Available]. PMID- 20294034 TI - [Not Available]. PMID- 20294035 TI - [Not Available]. PMID- 20294036 TI - [Not Available]. PMID- 20294037 TI - [Not Available]. PMID- 20294038 TI - [Not Available]. PMID- 20294039 TI - [Not Available]. PMID- 20294040 TI - Tuberculin surveys and the tuberculin test. PMID- 20294041 TI - The treatment of minimal tuberculous chest lesions; a comparative study. PMID- 20294042 TI - Some clinical and pathological aspects of tuberculosis of the central nervous system. PMID- 20294043 TI - House Sanatorium, Northhamptonshire. PMID- 20294044 TI - Preliminary, graduation and combined collapse therapy in pulmonarytuberculosis. PMID- 20294046 TI - A transition in viewpoint of certain intimate mechanisms of tuberculosis. PMID- 20294045 TI - Hemangioma of the bronchus with report of case. PMID- 20294047 TI - Rehabilitation for the tuberculous patient. PMID- 20294048 TI - [Not Available]. PMID- 20294049 TI - [Not Available]. PMID- 20294050 TI - [Not Available]. PMID- 20294051 TI - [Not Available]. PMID- 20294052 TI - [Not Available]. PMID- 20294053 TI - [Not Available]. PMID- 20294054 TI - [Not Available]. PMID- 20294055 TI - [Not Available]. PMID- 20294057 TI - [Not Available]. PMID- 20294056 TI - [Not Available]. PMID- 20294058 TI - WHAT'S in a name? PMID- 20294059 TI - History of the cat. PMID- 20294060 TI - Sulfathalidine in swine enteritis; further observations regarding the management of enteritis among feeder pigs with sulfathalidine. PMID- 20294061 TI - Hormone treatment of apparent senility in dogs. PMID- 20294062 TI - Penicillin in the treatment of Erysipelothrix rhusiopathiae-infected turkeys. PMID- 20294063 TI - Salmonellosis of turkeys. PMID- 20294064 TI - Veterinary contributions to BCG vaccination. PMID- 20294065 TI - Insect and livestock parasite control. PMID- 20294066 TI - Atypical lesions of blackleg. PMID- 20294067 TI - Photosensitization in cattle. PMID- 20294068 TI - Unusual case of amputation of a digit in a bull. PMID- 20294069 TI - Delivery of a 194 pound bovine fetus. PMID- 20294071 TI - Interphase (resting) nuclei, chromosomal vesicles and amitosis. PMID- 20294070 TI - Endometritis and neoplasms in a dog. PMID- 20294072 TI - Studies on lung tissue in vitro with special reference to the nature of the lining cells of the alveolus. PMID- 20294073 TI - Mitotic rate in mouse liver following intraperitoneal injection of liver, kidney and egg yolk. PMID- 20294074 TI - Comparison of the distribution of an hexosediphosphatase with glycerophosphatase in different tissues. PMID- 20294075 TI - Effect of gonad removal on the anterior pituitary of the fowl from 10 days to 6 years. PMID- 20294076 TI - The influence of maternal hormones on the reproductive organs of suckling rats. PMID- 20294077 TI - The action of male and female sex hormones on the adrenals in the fowl. PMID- 20294080 TI - The early development of the rostellum of Cysticercus fasciolaris Rud., and the chemical nature of its hooks. PMID- 20294081 TI - Studies on the genus Hymenolepsis, with descriptions of three new species. PMID- 20294082 TI - The life cycle of Diphyllobothrium oblongatum Thomas, a tapeworm of gulls. PMID- 20294083 TI - A critical review of terminology for immature stages in acanthocephalan life histories. PMID- 20294084 TI - On the occurrence of the acanthocephalan genus Telosentis in North America. PMID- 20294085 TI - The effects of cold temperature on the eggs of Schistosoma japonicum. PMID- 20294087 TI - Relative efficiency of six species of mosquitoes from Guam, M. I., as developmental hosts for Dirofilaria immitis. PMID- 20294086 TI - A method for providing a constant supply of tropical rat mites, Liponyssus bacoti, infected with the cotton rat filaria, Litosomoides carinii. PMID- 20294088 TI - The nemertean Carcinonemertes as an indicator of the spawning history of the host, Callinectes sapidus. PMID- 20294089 TI - Sarcocystis in Macaca mulatta. PMID- 20294090 TI - The rate of multiplication of Endamoeba histolytica and its relation to in vitro drug testing and possibly to nutritional studies. PMID- 20294091 TI - Failure of Aedes aegypti and Culex pipiens to transmit Plasmodium vaughani. PMID- 20294092 TI - An electron microscope study of mutation in tobaccomosaic virus. PMID- 20294093 TI - Stability of labile viruses in desiccated tissue. PMID- 20294094 TI - Effects of hydrogen peroxide produced in the medium by radiation on spermatozoa of Arbacia punctulata. PMID- 20294095 TI - Decomposition and regeneration of nitrogenous organic matter in sea water; the effect of enzyme poisons. PMID- 20294096 TI - The behavior and metamorphosis of the larva of Bugula neritina (Linnaeus); experimental modification of the length of the free-swimming period and the responses of the larvae to light and gravity. PMID- 20294097 TI - Variations of the submicroscopic structure of the cortical layer of fertilized and parthenogenetic sea urchin eggs. PMID- 20294098 TI - Physiological observations upon a larval Eustrongylides; influence of oxygen tension on the aerobic and post-anaerobic oxygen consumption. PMID- 20294099 TI - Development of secondary sexual characters in thyroidectomized brown Leghorn hens. PMID- 20294100 TI - The effects of nitrogen mustard on embryonic amphibian development; ectodermal effects. PMID- 20294101 TI - Quantitative studies on the locomotor capacity of larval Amblystoma (A. jeffersonianum) lacking Mauthner's neuron or the ear. PMID- 20294102 TI - A spectrophotometric study of a developing egg (Orthoptera) with especial reference to riboflavin and its derivatives. PMID- 20294103 TI - Induced neurosecretion in Lumbricus terrestris. PMID- 20294104 TI - Histological and histochemical observations upon an aberrant annelid, Poeobius meseres Heath. PMID- 20294105 TI - Morphological studies on glycogen deposition in schistosomes and other flukes. PMID- 20294106 TI - Morphogenesis, crenation and cytolytic reactions of the erythrocytes of amphibians. PMID- 20294107 TI - Studies on transplanted embryonic limbs of the chick; the replacement of muscle by adipose tissue. PMID- 20294108 TI - The computation of microbiological assays of amino-acids and other growth factors. PMID- 20294109 TI - Recent developments in apparatus for pH measurements and electrotitrations. PMID- 20294110 TI - Some applications of electrometric methods in analysis. PMID- 20294111 TI - Polarisation end-points. PMID- 20294112 TI - Spot-tests for the detection of alloying elements in zinc-base alloys. PMID- 20294113 TI - Spot-tests for the detection of alloying elements in lead-base alloys. PMID- 20294114 TI - The ratio of the capture cross-sections of lithium and boron for thermal neutrons. PMID- 20294115 TI - Evidence for an (eta, alpha) reaction induced in O17 by thermal neutrons. PMID- 20294116 TI - The foundations and philosophical implications of wave mechanics. PMID- 20294117 TI - The influence of the physical properties of sodium soaps on their dispersions in mineral oil. PMID- 20294118 TI - The flow properties of some anhydrous sodium soaps. PMID- 20294119 TI - A note on the use of multi-tip electrodes in polarographic work. PMID- 20294120 TI - The thermal decomposition of hydrogen peroxide vapour. PMID- 20294121 TI - Studies on reactions relating to carbohydrates and polysaccharides; effect of hot alkali on the nitrates of starch, amylose, and amylopectin. PMID- 20294122 TI - Studies on reactions relating to carbohydrates and polysaccharides; the stability of maltose and cellobiose octanitrates. PMID- 20294123 TI - Tertiary mercaptans as modifiers in GR-S polymerizations. PMID- 20294124 TI - The equilibrium diagrams and crystallization velocities of the systems: picric acid-2,4-dinitrophenol; di-nitrophenol-trinitrotoluene; picric acid-dinitrophenol trinitrotoluene. PMID- 20294125 TI - [Not Available]. PMID- 20294126 TI - [Not Available]. PMID- 20294127 TI - [Not Available]. PMID- 20294128 TI - [Not Available]. PMID- 20294129 TI - [Not Available]. PMID- 20294130 TI - [Not Available]. PMID- 20294131 TI - [Not Available]. PMID- 20294132 TI - [Not Available]. PMID- 20294133 TI - [Not Available]. PMID- 20294134 TI - [Not Available]. PMID- 20294135 TI - [Not Available]. PMID- 20294136 TI - [Not Available]. PMID- 20294137 TI - [Not Available]. PMID- 20294138 TI - [Not Available]. PMID- 20294140 TI - [Not Available]. PMID- 20294139 TI - [Not Available]. PMID- 20294141 TI - [Not Available]. PMID- 20294142 TI - [Not Available]. PMID- 20294143 TI - [Not Available]. PMID- 20294144 TI - [Not Available]. PMID- 20294145 TI - [Not Available]. PMID- 20294146 TI - [Not Available]. PMID- 20294147 TI - [Not Available]. PMID- 20294148 TI - [Not Available]. PMID- 20294149 TI - [Not Available]. PMID- 20294150 TI - [Not Available]. PMID- 20294151 TI - [Not Available]. PMID- 20294152 TI - [Not Available]. PMID- 20294153 TI - [Not Available]. PMID- 20294154 TI - [Not Available]. PMID- 20294155 TI - [Not Available]. PMID- 20294156 TI - [Not Available]. PMID- 20294157 TI - [Not Available]. PMID- 20294158 TI - [Not Available]. PMID- 20294159 TI - [Not Available]. PMID- 20294160 TI - [Not Available]. PMID- 20294161 TI - [Not Available]. PMID- 20294162 TI - [Not Available]. PMID- 20294163 TI - [Not Available]. PMID- 20294164 TI - [Not Available]. PMID- 20294165 TI - [Not Available]. PMID- 20294166 TI - [Not Available]. PMID- 20294167 TI - [Not Available]. PMID- 20294168 TI - [Not Available]. PMID- 20294169 TI - [Not Available]. PMID- 20294170 TI - [Not Available]. PMID- 20294171 TI - [Not Available]. PMID- 20294172 TI - [Not Available]. PMID- 20294173 TI - [Not Available]. PMID- 20294174 TI - [Not Available]. PMID- 20294175 TI - [Not Available]. PMID- 20294176 TI - [Not Available]. PMID- 20294177 TI - [Not Available]. PMID- 20294178 TI - [Not Available]. PMID- 20294179 TI - [Not Available]. PMID- 20294180 TI - [Not Available]. PMID- 20294181 TI - [Not Available]. PMID- 20294182 TI - [Not Available]. PMID- 20294183 TI - [Not Available]. PMID- 20294184 TI - [Not Available]. PMID- 20294185 TI - [Not Available]. PMID- 20294186 TI - [Not Available]. PMID- 20294187 TI - [Not Available]. PMID- 20294188 TI - [Not Available]. PMID- 20294189 TI - [Not Available]. PMID- 20294190 TI - [Not Available]. PMID- 20294191 TI - [Not Available]. PMID- 20294192 TI - [Not Available]. PMID- 20294193 TI - [Not Available]. PMID- 20294194 TI - [Not Available]. PMID- 20294195 TI - [Not Available]. PMID- 20294196 TI - [Not Available]. PMID- 20294197 TI - [Not Available]. PMID- 20294198 TI - [Not Available]. PMID- 20294199 TI - [Not Available]. PMID- 20294200 TI - [Not Available]. PMID- 20294201 TI - [Not Available]. PMID- 20294202 TI - [Not Available]. PMID- 20294203 TI - [Not Available]. PMID- 20294204 TI - [Not Available]. PMID- 20294205 TI - [Not Available]. PMID- 20294206 TI - [Not Available]. PMID- 20294207 TI - [Not Available]. PMID- 20294208 TI - [Not Available]. PMID- 20294209 TI - [Not Available]. PMID- 20294210 TI - [Not Available]. PMID- 20294211 TI - [Not Available]. PMID- 20294212 TI - [Not Available]. PMID- 20294213 TI - [Not Available]. PMID- 20294214 TI - Limitations of the Newtonian time scale in relation to non-equilibrium rheological states and a theory of quasi-properties. PMID- 20294215 TI - Kinetic boundary friction. PMID- 20294216 TI - A general kinetic theory of liquids; equilibrium properties. PMID- 20294217 TI - Radiative equilibrium in the ionosphere. PMID- 20294219 TI - What is anatomy? PMID- 20294218 TI - Visual adaptation in relation to brief conditioning stimuli. PMID- 20294220 TI - Functions of the teeth. PMID- 20294221 TI - Penicillin and root canal therapy. PMID- 20294222 TI - Penicillin in root therapy. PMID- 20294223 TI - The necessity of histological examination of all tissue removed at operation; a case of squamous carcinoma of the maxilla. PMID- 20294224 TI - The limitations of orthodontic treatment; diagnosis and treatment in the permanent dentition. PMID- 20294225 TI - Indications for the removal of impacted third molars at an early age. PMID- 20294226 TI - Overbite cases. PMID- 20294227 TI - The use of antibiotics in mixed infections; report of two cases. PMID- 20294228 TI - Tumors of the mandibular condyle; report of two cases. PMID- 20294229 TI - Ossifying fibroma of mandible treated by excision. PMID- 20294230 TI - Unilateral parotid swelling with fistula. PMID- 20294231 TI - Enucleation of odontogenic cyst, with pathologic fracture and submandibular infection treated by drainage, penicillin therapy and skeletal fixation. PMID- 20294232 TI - Lipoma causing facial deformity. PMID- 20294233 TI - Extensive epidermoid carcinoma of the mandibular gingiva with invasion of the bone and floor of the mouth treated by partial jaw resection; insertion of tantalum plate, and prosthesis. PMID- 20294234 TI - Some common problems shared by the dentist and the cardiologist. PMID- 20294235 TI - Anesthesia considerations in oral surgery and dentistry. PMID- 20294236 TI - Trigeminal neuralgia; its present status in dental and neurological surgery. PMID- 20294237 TI - The role of penicillin and streptomycin in oral infections. PMID- 20294238 TI - Possible methods of controlling dental pain. PMID- 20294239 TI - Experimental investigations of parodontal disease; gnawing of sugar cane in the treatment of non-ulcerative gingival disease in man. PMID- 20294240 TI - Clinical and microscopical observations in the treatment of Vincent's infection with penicillin. PMID- 20294241 TI - An haemangioma of the upper lip. PMID- 20294242 TI - Dental pain while flying or during decompression tests. PMID- 20294243 TI - The extraction of teeth, deciduous and permanent, in the causation and treatment of malocclusion. PMID- 20294244 TI - Early women dentists. PMID- 20294245 TI - Localisation of buried roots and foreign bodies within the mandible or maxilla. PMID- 20294246 TI - Gnawing of sugar cane. PMID- 20294247 TI - Characteristic morphological changes in Bacillus fusiformis in the course of penicillin treatment. PMID- 20294248 TI - The Bristol Dental School, 1874-1940. PMID- 20294249 TI - Consolidation of a cancellous bone graft. PMID- 20294250 TI - ADVERTISING in the eighteenth century. PMID- 20294251 TI - Positional variations of the teeth in animals. PMID- 20294252 TI - A new orthodontic appliance. PMID- 20294253 TI - Sodium fluoride paste as a desensitising agent for hypersensitive dentine. PMID- 20294254 TI - A study and treatment of subluxation of the temporomandibular articulation. PMID- 20294255 TI - Pericoronitis of third molars. PMID- 20294256 TI - Penicillin in oral infections. PMID- 20294257 TI - The prosthetic dental laboratory problem. PMID- 20294258 TI - Cyclopropane anesthesia. PMID- 20294259 TI - The use of psychology in the management of the difficult patient. PMID- 20294260 TI - The manipulation of some common materials used in operative dentistry. PMID- 20294261 TI - Progress in caries research. PMID- 20294263 TI - Some psychosomatic aspects of medicine. PMID- 20294262 TI - Some thoughts concerning the carrying out of minor dental operations under general anaesthesia. PMID- 20294264 TI - Apicoectomy of anterior teeth. PMID- 20294265 TI - Harmonizing professional service and business management of a dental practice. PMID- 20294266 TI - Diagnostic oral roentgenology. PMID- 20294267 TI - Surgery of the mouth and jaws. PMID- 20294268 TI - Impacted and aberrant teeth; their history, causes and treatment. PMID- 20294269 TI - The plastics; with special emphasis on the use of acrylics in the construction of jacket crowns, bridgework and partial dentures. PMID- 20294270 TI - Practical dental assisting. PMID- 20294271 TI - Why not consider most mouth pathology as part of a syndrom? PMID- 20294272 TI - An acrylic, splint to relieve painful tongue symptoms. PMID- 20294273 TI - The newer knowledge of hygiene in diet. PMID- 20294274 TI - Antibiotics and infections of the oral mucosa. PMID- 20294275 TI - Gelfoam in dentistry; a preliminary report. PMID- 20294276 TI - The newer knowledge of hygiene in diet. PMID- 20294277 TI - The doctor says it's just my nerves. PMID- 20294278 TI - Some psychosomatic aspects of medicine. PMID- 20294279 TI - Cleft palate prosthesis. PMID- 20294280 TI - Harmonizing professional service and business management of a dental practice. PMID- 20294281 TI - Surgery of the mouth and jaws. PMID- 20294282 TI - Impacted and aberrant teeth; their history, causes and treatment. PMID- 20294283 TI - The plastics; with special emphasis on the use of acrylics in the construction of jacket crowns, bridgework and partial dentures. PMID- 20294284 TI - Diagnostic oral roentgenology. PMID- 20294285 TI - The use of optical loupes in dentistry. PMID- 20294286 TI - Dental interest in palaeontology and anthropology. PMID- 20294287 TI - An interesting case of cleft palate and hare lip. PMID- 20294288 TI - The teeth of the Kabyles. PMID- 20294289 TI - Identification by teeth and jaws; a survey. PMID- 20294291 TI - A correct method of toothbrushing. PMID- 20294290 TI - The use of metals for the treatment of mandibular fractures. PMID- 20294293 TI - Clinical application of techniques in local anesthesia. PMID- 20294292 TI - Pertinent points about penicillin. PMID- 20294294 TI - Important considerations in porcelain veneer restorations. PMID- 20294295 TI - Mouth breathing as a primary etiologic factor in the production of malocclusion. PMID- 20294296 TI - A point of view toward orthodontic treatment. PMID- 20294297 TI - Vitamin K; its relationship to dental conditions. PMID- 20294298 TI - Teething and its significance. PMID- 20294299 TI - Toothbrushing; its effect on gingival tissues. PMID- 20294300 TI - The physical and chemical properties of silver amalgam. PMID- 20294301 TI - The influence of sodium bisulphite on acid production in saliva. PMID- 20294302 TI - Dental caries and tryptophane deficiency. PMID- 20294303 TI - A note on the duration of caries inhibition produced by fluoride applications. PMID- 20294304 TI - Solubility of enamel as affected by fluorides of varying pH. PMID- 20294305 TI - Solubility of enamel protected by sodium fluoride and other compounds. PMID- 20294306 TI - The role of roentgenograms in public health dental surveys. PMID- 20294307 TI - Capacity of periodontal vessels on pressure and tension sides of teeth moved by orthodontic appliances. PMID- 20294308 TI - Experimental amelotomy; report of ground section study. PMID- 20294309 TI - Induced fuso-spirochetal infection in dogs. PMID- 20294310 TI - Bilateral dens in dente. PMID- 20294311 TI - Psychosomatic factors in the etiology of periodontal disease. PMID- 20294312 TI - The effect of the temporal muscle on the form of the mandibles. PMID- 20294313 TI - Space maintainers. PMID- 20294314 TI - Dentistry in South Africa. PMID- 20294315 TI - A basic approach to the problem of gingival disease. PMID- 20294316 TI - Greek individualism triumphs for 2,000 years. PMID- 20294317 TI - Endodontia in dental education. PMID- 20294318 TI - Processing acrylic dentures. PMID- 20294319 TI - The value of a hospital survey. PMID- 20294320 TI - When to start orthodontic treatment considering age and relative growth. PMID- 20294321 TI - Treatment of mycosis fungoides with nitrogen mustard. PMID- 20294322 TI - A method for protection of patients with solar urticaria. PMID- 20294323 TI - Somato-psychic medicine. PMID- 20294324 TI - Treatment of penile condylomato acuminata with podophyllin; observations on the prevention of balanitis. PMID- 20294325 TI - Photosensitization in the treatment of psoriasis. PMID- 20294326 TI - Penicillin ointments; a study of the effect of ointment ingredients on the stability of penicillin. PMID- 20294327 TI - Exudative discoid and lichenoid chronic dermatosis (Sulzberger-Garbe) histopathologic study. PMID- 20294328 TI - Polyethylene glycol vehicles in dermatology. PMID- 20294329 TI - The medicolegal use of the acid phosphatase test for the identification of seminal stains. PMID- 20294330 TI - Laboratory examination for protozoa. PMID- 20294331 TI - Permanent staining with iron-haematoxylin. PMID- 20294333 TI - Evaluation of surface pH as a freshness index for fish fillets. PMID- 20294332 TI - A practical technique for calcium and phosphorus estimations. PMID- 20294335 TI - Rehydration of dehydrated meat. PMID- 20294334 TI - A study of yeast growth-promoting substances in white sugar. PMID- 20294336 TI - Carbohydrates in cultivated mushrooms (Agaricus campestris). PMID- 20294337 TI - A study of butyric acid-producing anaerobes isolated from spoiled canned tomatoes. PMID- 20294338 TI - Pectinic acids as related to texture and quality of dehydrated fruit products. PMID- 20294339 TI - Evaluation of carotene content of fresh and cooked spinach. PMID- 20294340 TI - Growth of Staphylococcus aureus in various pastry fillings. PMID- 20294341 TI - Effect of fertilizer treatment on total and reduced ascorbic acid content of potato tubers. PMID- 20294342 TI - Variations in composition of frankfurters with special reference to cooking changes. PMID- 20294343 TI - Relation of tenderness of beef to aging time at 33-35 degrees F. PMID- 20294344 TI - The growth of the odontoblasts of the incisor tooth as a criterion of the vitamin C intake of the guinea pig. PMID- 20294345 TI - The renal threshold for ascorbic acid; a modified method for its estimation with results for 12 adult subjects. PMID- 20294346 TI - Plasma levels and urinary excretion of ascorbic acid in women during the menstrual cycle. PMID- 20294347 TI - Biotin balance in the albino rat. PMID- 20294348 TI - A study of ascorbic acid metabolism of adolescent children. PMID- 20294349 TI - A study of sex differences in the composition of rats, with emphasis on the lipid component; sex difference in susceptibility to essential fatty acid deficiency with high and low fat diets. PMID- 20294350 TI - Amino acid content of feeds; leucine, valine, isoleucine and phenylalanine. PMID- 20294351 TI - The role of B6-deficiency in the tryptophane-niacin relationships in rats. PMID- 20294352 TI - The effect of fat level of the diet on general nutrition; growth, reproduction and physical capacity of rats receiving diets containing various levels of cottonseed oil or margarine fat ad libitum. PMID- 20294353 TI - The effect of fat level of the diet on general nutrition; growth, mortality and recovery in weanling rats maintained on restricted calories. PMID- 20294354 TI - The net protein value of food yeast. PMID- 20294355 TI - Nutritional survey at a children's institution; incidence of avitaminotic lesions and effects of therapy. PMID- 20294356 TI - An instructive case of treated hepatic disease, with a 27-year follow-up. PMID- 20294357 TI - Diabetes mellitus, fibrocongestive splenomegaly (Banti's syndrome) and infectious mononucleosis. PMID- 20294358 TI - A soluble phenolphthalein laxative. PMID- 20294359 TI - Giant hypertrophic gastritis. PMID- 20294360 TI - The effect of vagotomy on gastric function. PMID- 20294361 TI - The rate of healing of gastric ulcers. PMID- 20294362 TI - Syndrome on non tropical sprue with hitherto undescribed lesions of the intestine. PMID- 20294363 TI - Oral cholecystography with priodax; correlation with pathologic findings. PMID- 20294364 TI - A preliminary report on protein hydrolysate therapy for peptic ulcer. PMID- 20294365 TI - Protein hydrolysate therapy for peptic ulcer; report on 26 cases. PMID- 20294366 TI - Nonreactive aluminum hydroxide in the treatment of peptic ulcer. PMID- 20294367 TI - Complications following war wounds of the abdomen. PMID- 20294368 TI - The treatment of war wounds involving the gastrointestinal tract. PMID- 20294369 TI - Primary megacolon. PMID- 20294370 TI - A simplified procedure for the determination of pepsin and trypsin concentrations in digestive juices. PMID- 20294371 TI - [Multiple myeloma]. PMID- 20294372 TI - Case report of supposed recurrent pancreatitis. PMID- 20294373 TI - Surgical treatment of lesions of the lower bowel. PMID- 20294374 TI - Discussion of malignancy of the lower gastrointestinal tract. PMID- 20294375 TI - Modern gastroscopy; observations. PMID- 20294376 TI - The pathogenetic nature of the hepatic cirrhoses. PMID- 20294377 TI - Effect of ascorbic acid upon cinchophen experimental peptic ulcer. PMID- 20294378 TI - American journals of gastroenterological interest and some historical notes. PMID- 20294379 TI - SUGGESTED standards of acceptance for medical care plans approved by the Council on Medical Service of the A.M.A. PMID- 20294380 TI - Review of the literature of 1944 to 1946 on malignancy of the colon and rectum. PMID- 20294381 TI - Review of proctologic literature for 1944 and 1945; nonmalignant diseases. PMID- 20294382 TI - The posterior levator space; its relation to postanal infection. PMID- 20294383 TI - Relationship between anorectal and colonic conditions. PMID- 20294384 TI - The clover leaf operation for pruritus ani. PMID- 20294386 TI - A review of the problem of chronic ulcerative colitis. PMID- 20294385 TI - Two-team abdomino-perineal operation for carcinoma of rectum and rectosigmoid. PMID- 20294387 TI - Indications for primary closure after excision of pilonidal cysts. PMID- 20294388 TI - The management of recurrent pilonidal disease. PMID- 20294389 TI - Pilonidal disease; an open method of operation. PMID- 20294390 TI - The reduction in morbidity and the prevention of complications in proctology. PMID- 20294391 TI - Radon ointment therapy of late irradiation lesions of the rectosigmoid colon (preliminary report). PMID- 20294392 TI - Diverticulitis. PMID- 20294393 TI - Management of vesical dysfunction in anorectal disease. PMID- 20294394 TI - The value of periodic rectosigmoidoscopic examination in the prevention of lower bowel malignancy. PMID- 20294396 TI - Pilonidal sinus simulating anal fistula. PMID- 20294395 TI - Villous papilloma associated with multiple rectal adenomata without evidence of extension to colon. PMID- 20294397 TI - Gunshot wound of the extraperitoneal. PMID- 20294398 TI - Multiple cysts of the sacrococcygeal anal region. PMID- 20294399 TI - Leiomyoma of the rectum. PMID- 20294400 TI - Pigmentation and hair growth in black rats, as modified by the chronic administration of thiourea, phenyl thiourea and alphanaphthyl thiourea. PMID- 20294402 TI - The effect of vagotomy and of thoracic sympathectomy on the blood glucose changes in dogs given alloxan. PMID- 20294401 TI - Differentiation of the antithyroid action of thiouracil, thiourea and paba from sulfonamides by iodide administration. PMID- 20294403 TI - Inhibition of thyroid function in beagle puppies by propylthiouracil without disturbance of growth or health. PMID- 20294404 TI - The relation of the hypophysis, ovary, placenta and fetus to the development of anemia during the last half of pregnancy in the rat. PMID- 20294405 TI - Estrogenic activity of rabbit whold blood determined by the intravaginal pellet method. PMID- 20294406 TI - The effect of the prostate and seminal vesicle on the production of hyaluronidase by rat testes homogenate. PMID- 20294407 TI - The effects of gonadectomy and the administration of testosterone propionate on the growth of antlers in male and female deer. PMID- 20294408 TI - The reaction of the male South African clawed frog (Xenopus laevis) to gonadotropins. PMID- 20294409 TI - Gonadotropic hormone; comparison of ultrafiltration and alcohol-precipitation methods of recovery from urine. PMID- 20294410 TI - Three unusual endocrinopathies with associated ovarian pathology; ovarian agenesis; precocious puberty; virilism. PMID- 20294411 TI - Paroxysmal hypertension with concomitant swelling of the thyroid due to pheochromocytoma of the right adrenal gland; cure by surgical removal of the pheochromocytoma. PMID- 20294412 TI - The effect of thiouracil derivatives of fetuses and infants. PMID- 20294413 TI - Thyroid and adrenal interrelations with special reference to hypotrichosis axillaris in thyrotoxicosis. PMID- 20294415 TI - Research in cardiovascular diseases. PMID- 20294414 TI - A bill of rights for old age. PMID- 20294416 TI - The length of life in ancient Greece. PMID- 20294417 TI - The oral glucose tolerance test in old men. PMID- 20294418 TI - Program of research on aging of the skin. PMID- 20294419 TI - Pathologic changes of old age. PMID- 20294420 TI - Conditions desirable for the rapid progress of gerontological research. PMID- 20294421 TI - Chronic progressive subcortical encephalopathy; report of a case. PMID- 20294422 TI - Ovarian changes with aging. PMID- 20294423 TI - Care of the chronic ill. PMID- 20294424 TI - Toxic goiter in the aged. PMID- 20294425 TI - Age and fowl tumors. PMID- 20294426 TI - Winter ailments of the old. PMID- 20294427 TI - Menorrhagia associated with irregular shedding of the endometrium; a clinical and experimental study. PMID- 20294428 TI - A study of the physiologic action of human chorionic hormone; the production of pseudopregnancy in women by chorionic hormone. PMID- 20294429 TI - Combined evipal and scopolamine analgesia and cyclopropane anesthesia in obstetrics. PMID- 20294430 TI - Surgical geriatric gynecology. PMID- 20294431 TI - Stress incontinence in the female. PMID- 20294432 TI - Puerperal gynecology; a report of thirty years' experience with gyneplastic repair operations immediately after childbirth. PMID- 20294433 TI - Constriction ring dystocia. PMID- 20294434 TI - Minimal spinal anesthesia in vaginal delivery; an analysis of 1,000 consecutive cases. PMID- 20294435 TI - The management of delivery following stillbirth from previous dystocia. PMID- 20294436 TI - Blood calcium; a normal curve for pregnancy. PMID- 20294437 TI - Experience with midpelvic dystocia; preliminary report. PMID- 20294438 TI - An evaluation of the criteria of diagnosis and cure of gonorrhea in the female. PMID- 20294439 TI - Penicillin and acute puerperal mastitis. PMID- 20294440 TI - A 55-pound solid uterine myoma. PMID- 20294441 TI - Leiomyofibroma of the uterus and endometrial carcinoma. PMID- 20294442 TI - A study of the inter-action of pregnancy and hypertensive disease. PMID- 20294443 TI - Placental metabolism of vitamin C; histochemical analysis. PMID- 20294444 TI - Pregnancy and the double uterus. PMID- 20294445 TI - Spontaneous annular detachment of the cervix during labor. PMID- 20294446 TI - Subacute bacterial endocarditis during pregnancy. PMID- 20294447 TI - Syphilis in pregnancy treated by penicillin. PMID- 20294448 TI - Tubal and uterine twin pregnancy. PMID- 20294449 TI - Marginal placenta previa treated by artificial rupture of the membranes 39 days before vaginal delivery. PMID- 20294450 TI - True knot in the umbilical cord causing death of monoamniotic twins in a primipara before labor. PMID- 20294451 TI - The place of myomectomy in the treatment of myoma uteri. PMID- 20294452 TI - Bibliopegia fantastica. PMID- 20294453 TI - Oral hygiene in the ancient and medieval Orient. PMID- 20294454 TI - The care of the mouth in Greece and Rome. PMID- 20294455 TI - Oral hygiene in the medieval Occident. PMID- 20294456 TI - Medical apprenticeship in the American Colonies. PMID- 20294458 TI - Medical schools in the Colonies. PMID- 20294457 TI - European influences in Colonial medicine. PMID- 20294459 TI - Early history of Psi Omega Fraternity. PMID- 20294460 TI - A brief history of Psi Omega's publications. PMID- 20294461 TI - Gallbladder disease. PMID- 20294462 TI - Infant feeding. PMID- 20294463 TI - Some thoughts on the relation of physiology of bone to the interpretation of roentgenograms. PMID- 20294464 TI - Roentgenological aspects of the ruptured intervertebral disk. PMID- 20294465 TI - X-ray therapy of spondylitis and the arthritides. PMID- 20294466 TI - Classification of tumors with reference to radiosensitivity. PMID- 20294467 TI - Research on cancer in the Orient. PMID- 20294468 TI - Hospital architecture, yesterday and today. PMID- 20294469 TI - Laundry problems in the hospital. PMID- 20294470 TI - Cancer, the spectre of waste. PMID- 20294471 TI - Certification of all laboratory technologists desirable in public interest. PMID- 20294472 TI - Aims of the Canadian Society of Radiological Technicians. PMID- 20294473 TI - Anatomical figurines; a neglected chapter in the history of anatomical illustration and instruction. PMID- 20294474 TI - The case of group practice. PMID- 20294475 TI - Administrative responsibility for the control of surgery. PMID- 20294476 TI - There are ogres in in the hospital basement. PMID- 20294477 TI - Experiment in integration; medical college and teaching hospital function as one. PMID- 20294479 TI - FUNCTIONAL basis of hospital planning. PMID- 20294478 TI - Use is the ultimate test of good medical records. PMID- 20294481 TI - When the healthmobile came calling advance publicity ensured its welcome. PMID- 20294480 TI - Population trends in mental hospitals. PMID- 20294482 TI - The public's responses to matters of health. PMID- 20294483 TI - The dietitian as a buyer. PMID- 20294484 TI - Studies on botulinum toxoids, types A and B; immunization of man. PMID- 20294485 TI - The quantitative estimation of egg and chicken proteins in equine encephalomyelitis vaccines. PMID- 20294486 TI - Some relations between equine encephalomyelitis virus (Eastern type) and normal host cellular constituents. PMID- 20294487 TI - A quantitative study of the Arthus phenomenon induced passively in the rabbit. PMID- 20294488 TI - The effect of metabolites, metabolite antagonists and enzyme-inhibitors on the growth of the vaccinia virus in Maitland type of tissue cultures. PMID- 20294489 TI - Complement-fixing antibodies of lymphogranuloma venereum in mice; their development and response to sulfonamide therapy. PMID- 20294490 TI - Dysentery; a progress report for the years 1942 to 1946. PMID- 20294491 TI - Outline analysis of research problems in industrial physiology. PMID- 20294492 TI - Facts and fallacies concerning exposure to lead. PMID- 20294493 TI - Public exposure to lead. PMID- 20294494 TI - Clinical significance of hematologic changes in lead absorption and lead poisoning. PMID- 20294495 TI - Exposure to lead. PMID- 20294496 TI - Industrial hernias. PMID- 20294497 TI - How plant medical service can help industry. PMID- 20294498 TI - How to procure a plant medical service. PMID- 20294499 TI - UNESCO. PMID- 20294500 TI - Peacetime uses of atomic energy. PMID- 20294501 TI - Social insurance versus poor relief. PMID- 20294502 TI - Immigrant adjustment in Yankee City. PMID- 20294503 TI - Some impressions of Sungei Buloh Leper Hospital under Japanese occupation. PMID- 20294504 TI - Notes on leprosy settlements; Tanganyika Territory. PMID- 20294505 TI - Leprosy survey of school children in British Guiana. PMID- 20294506 TI - Mechanism of endocrine allergy; interpretation of principal phenomena observed in hypersensitivity to the endogenous hormones. PMID- 20294507 TI - Rheumatic fever following athletic trauma. PMID- 20294508 TI - An observation concerning the hands of patients with rheumatic fever. PMID- 20294509 TI - A method for repeated measurements of venous pressure. PMID- 20294510 TI - Ophthalmia in Cyprus; two historical notices. PMID- 20294511 TI - Medical and vital statistics. PMID- 20294512 TI - [Not Available]. PMID- 20294513 TI - [Not Available]. PMID- 20294514 TI - [Not Available]. PMID- 20294515 TI - [Not Available]. PMID- 20294516 TI - On the effect of pericardial effusion on the electrocardiogram. PMID- 20294517 TI - [Not Available]. PMID- 20294518 TI - [Not Available]. PMID- 20294519 TI - Streptomycin. PMID- 20294520 TI - Streptomycin; general considerations, tests for bacterial sensitivity and methods of measurement of streptomycin in body fluids. PMID- 20294521 TI - Streptomycin in tuberculosis. PMID- 20294522 TI - Use of streptomycin in the treatment of bacterial endocarditis. PMID- 20294523 TI - Streptomycin in peritonitis. PMID- 20294524 TI - Topical use of streptomycin in wounds. PMID- 20294525 TI - The present status of treatment for influenzal meningitis. PMID- 20294526 TI - Treatment of tularemia with streptomycin. PMID- 20294527 TI - Treatment of urinary tract infections with streptomycin. PMID- 20294528 TI - Streptomycin therapy in undulant fever. PMID- 20294529 TI - Toxicity of streptomycin. PMID- 20294530 TI - Acute coronary artery diseases; history, incidence, differential diagnosis and occupational significance. PMID- 20294531 TI - Diagnostic value of roentgenography and fluoroscopy in the diagnosis of rheumatic heart disease. PMID- 20294532 TI - Electrocardiographic findings in rheumatic heart disease. PMID- 20294533 TI - Histoplasmosis; report of diagnosis from biopsy of cutaneous nodules. PMID- 20294534 TI - Congestive heart failure arising from uncontrolled auricular fibrillation in the otherwise normal heart; follow-up notes on a previously reported case. PMID- 20294536 TI - Chrysotherapy in pulmonary tuberculosis. PMID- 20294535 TI - A follow-up study of first 50 pre-frontal leucotomy cases. PMID- 20294537 TI - Anaemia. PMID- 20294538 TI - Thiamin syndrome in children. PMID- 20294539 TI - Discussion on floating specks. PMID- 20294540 TI - Dehydration. PMID- 20294541 TI - Indian food distress; its solution. PMID- 20294542 TI - My experience in treating ruptured uterus. PMID- 20294543 TI - Acute delirious convulsive meningism in ascariasis; a case note. PMID- 20294544 TI - An untreated case of acute conjunctivitis. PMID- 20294546 TI - Present status of the problem of amebiasis. PMID- 20294545 TI - Neurasthenia as a sequelae of intestinal amoebiasis. PMID- 20294548 TI - Bronchiogenic adenoma; benign tumor of the bronchus. PMID- 20294547 TI - Hemolytic streptococcic sore throat; the course of the acute disease. PMID- 20294549 TI - Primary hypertrophy and hyperplasia of the parathyroid glands associated with duodenal ulcer; report of an additional case, with special reference to metabolic, gastrointestinal and vascular manifestations. PMID- 20294550 TI - Coincidence of diabetes mellitus and hypopituitarism. PMID- 20294551 TI - Penicillin therapy of subacute bacterial endocarditis: a study of the end results in 34 cases, with particular reference to dosage, methods of administration, criteria for judging adequacy of treatment and probable reasons for failures. PMID- 20294552 TI - Treatment of Plasmodium vivax malaria of foreign origin; a comparison of various drugs. PMID- 20294553 TI - Coexisting tuberculosis and coccidioidomycosis. PMID- 20294554 TI - Septic staphylococcemia successfully treated by penicillin and bacteriophage. PMID- 20294555 TI - Hemolytic streptococcic sore throat; the post-streptococcic state. PMID- 20294556 TI - Cardiac failure in penicillin-treated subacute bacterial endocarditis. PMID- 20294557 TI - Mercurial diuretics; a comparison of acute cardiac toxicity in animals and the effect of ascorbic acid on detoxification in their intravenous administration. PMID- 20294558 TI - Experimentally induced infectious hepatitis; roentgenographic and gastroscopic observations. PMID- 20294559 TI - Epileptogenic effects of penicillin; an experimental study. PMID- 20294560 TI - Acute and chronic back pain. PMID- 20294561 TI - Resection of the vagus nerve for peptic ulcer. PMID- 20294562 TI - Psychosomatic problems in general medicine. PMID- 20294563 TI - Some problems in the field of medical economics. PMID- 20294564 TI - Diagnosis of non-traumatic intracranial lesions. PMID- 20294565 TI - Ocular torticollis. PMID- 20294571 TI - DIFFUSE vascular diseases. PMID- 20294572 TI - Liver function tests. PMID- 20294573 TI - Report of the Hutchinson Memorial Cancer Detection Clinic. PMID- 20294574 TI - Review of 422 cases of sterility in private practice. PMID- 20294575 TI - A changed concept of pelvic inflammation. PMID- 20294576 TI - Sterility in the male. PMID- 20294578 TI - Surgical treatment of pulmonary tuberculosis. PMID- 20294577 TI - Surgery of the thorax. PMID- 20294579 TI - Surgical conditions of heart and great vessels. PMID- 20294580 TI - Surgery or propyl thiouracil. PMID- 20294581 TI - Spread of influenza and encephalitis. PMID- 20294583 TI - Public relations of a state medical society. PMID- 20294582 TI - Sprue and sprue-like diarrhoeas with fat and carbohydrate intolerance. PMID- 20294588 TI - Rheumatic fever control program in California. PMID- 20294590 TI - Fractional spinal anesthesia for short upper abdominal surgery. PMID- 20294591 TI - Poison oak; new antigens and their effect on sensitized patients. PMID- 20294593 TI - Progress in the treatment of carcinoma of the prostate. PMID- 20294594 TI - Acute transient pancreatitis associated with chronic cholecystitis and cholelithiasis. PMID- 20294595 TI - Men like women doctors; there is encouragement for women to study medicine in that the public has learned they make good physicians. PMID- 20294596 TI - Optic atrophy in Hong Kong prisoners of war. PMID- 20294597 TI - Residual disabilities in Hong Kong repatriates. PMID- 20294598 TI - Preoperative and postoperative care of intestinal obstruction. PMID- 20294599 TI - Anaesthetic emergencies. PMID- 20294600 TI - Influenzal meningitis. PMID- 20294601 TI - Infectious mononucleosis; complications. PMID- 20294602 TI - Haemoglobin levels in Canadian population groups; children and young women. PMID- 20294603 TI - Cyanosis in infants in rural areas (well-water methaemoglobinaemia). PMID- 20294604 TI - Headache; treatment with histamine. PMID- 20294605 TI - Roentgenological localization of ureteral obstruction by non radio-opaque or indistinguishable calculi. PMID- 20294606 TI - Alloxan diabetes. PMID- 20294607 TI - Notes on cholecystectomy. PMID- 20294608 TI - Mucosal respiratory (Stevens-Johnson) syndrome. PMID- 20294609 TI - Skin tests in dermatology. PMID- 20294610 TI - Paediatric endocrinology. PMID- 20294611 TI - Ganglioneuroma of stomach. PMID- 20294612 TI - True unicornuate uterus and total absence of left broad ligament, round ligament, salpinx, ovary, kidney and ureter. PMID- 20294613 TI - Pulmonary type of tularaemia; two cases. PMID- 20294614 TI - Lymphatic leukaemia becoming aleukaemic. PMID- 20294615 TI - Thiamine chloride in pernicious anaemia. PMID- 20294616 TI - Medical applications of artificial radioactive isotopes. PMID- 20294617 TI - Relief of postanaesthetic vomiting through pyridoxine. PMID- 20294618 TI - The role of the hospital in medical economics. PMID- 20294621 TI - The history of psychiatric education in the United States from 1844 to 1944. PMID- 20294620 TI - Medical education, old purposes and new methods. PMID- 20294622 TI - The future of psychiatry in medical education. PMID- 20294619 TI - Fractures of the mandible. PMID- 20294623 TI - The history of medicine as a hobby; a brief bibliography of medical history. PMID- 20294624 TI - Studies on acquired tolerance to tartar emetic, antimony sodium thioglycollate and neostam. PMID- 20294625 TI - Humidity sensations in relation to moisture gradients between clothings. PMID- 20294626 TI - Undernutrition among Shanghai school children, preliminary report. PMID- 20294627 TI - Notes on the experimental infection of Culex pipiens var. pallens Coq. with Microfilaria malayl Brug. PMID- 20294628 TI - Fasciolopsis in guinea pigs with a summary of the definitive hosts. PMID- 20294630 TI - The isotopes in biology and medicine. PMID- 20294629 TI - A case of vitamin K deficiency. PMID- 20294631 TI - Photography as an aid to medical education. PMID- 20294632 TI - Protein metabolism in disease and injury. PMID- 20294633 TI - Granulocytopenia successfully treated by intramedullary bone marrow transfusion; report of two cases. PMID- 20294634 TI - Epidemiological studies in cholera. PMID- 20294635 TI - Epidemiological studies in cholera; duration of the convalescent carrier period in cholera. PMID- 20294636 TI - Epidemiological studies in cholera; secondary attack rate among cholera household contacts, China, 1946. PMID- 20294637 TI - Epidemiological studies in cholera; occupation, age, sex, secondary cases, vaccination, case fatality. PMID- 20294638 TI - China's proposals at the International Health Conference. PMID- 20294639 TI - Early cardiac signs of childhood rheumatism; practical aspects and significance. PMID- 20294640 TI - The problem of obesity. PMID- 20294641 TI - Place, in the geriatric regime. PMID- 20294642 TI - Conservative treatment of frontal sinusitis. PMID- 20294643 TI - Newer concepts in the treatment of diabetes mellitus. PMID- 20294644 TI - Streptococcic dissociation. PMID- 20294645 TI - Hyalinization of the seminiferous tubules with normal or falling Leydig cell function; a report of two cases. PMID- 20294646 TI - Intrabronchial administration of penicillin and sulphonamide. PMID- 20294647 TI - A case of glomerulonephritis with unilateral haematuria. PMID- 20294648 TI - Chronic subphrenic abscess. PMID- 20294649 TI - Medicine and national security. PMID- 20294650 TI - Pulmonary sarcoidosis. PMID- 20294651 TI - Ragweed pollen survey in Connecticut. PMID- 20294653 TI - The contribution of Yale University School of Medicine to the Connecticut cancer program. PMID- 20294652 TI - The Connecticut cancer record registry, how it functions. PMID- 20294654 TI - The use of a glass button in the treatment of ascites. PMID- 20294655 TI - An intern teaching program in a small hospital. PMID- 20294656 TI - Scarlet fever immunizations. PMID- 20294657 TI - ARMY MEDICAL LIBRARY acquires celebrated Chinese publication. PMID- 20294658 TI - INTERPRETATION of quantitative serological tests for syphilis. PMID- 20294659 TI - Leprosy and cockroaches. PMID- 20294660 TI - Dermatitis as a monosymptomatic manifestation of nicotinic acid deficiency. PMID- 20294661 TI - Tomography of bronchiectasis by means of pre-selected planes of section. PMID- 20294662 TI - Biliary tract surgery; a statistical study based upon 1070 consecutive cases. PMID- 20294663 TI - Edema and diuresis. PMID- 20294664 TI - Hodkin's disease and pregnancy; review of the literature and report of a case. PMID- 20294665 TI - Penicillin in the treatment of venereal disease. PMID- 20294666 TI - Infantile eczema. PMID- 20294667 TI - A case of bilateral pulmonary tuberculosis treated by artificial pneumoperitoneum with phrenic crush and contralateral artificial pneumothorax. PMID- 20294668 TI - WHALE meat. PMID- 20294669 TI - Chronic pain in the right iliac fossa. PMID- 20294671 TI - TROPICAL diseases and the medical student. PMID- 20294670 TI - Hepatitis. PMID- 20294672 TI - Goitre. PMID- 20294673 TI - CASE of acute myeloblastic leukaemia. PMID- 20294674 TI - The Constantine Hering Fund and Walter E. Hering Foundation of the Hahnemann Medical College and Hospital of Philadelphia. PMID- 20294675 TI - Fundamental aspects of fluid balance. PMID- 20294676 TI - Salt and water metabolism in pediatrics. PMID- 20294677 TI - Fluid balance in urology. PMID- 20294678 TI - Early ambulation in the practice of diseases in the ear, nose and throat. PMID- 20294679 TI - Encephalitis. PMID- 20294680 TI - Bronchiectasis. PMID- 20294682 TI - The laboratory aspects of infectious hepatitis. PMID- 20294681 TI - Interpretation of liver function tests. PMID- 20294683 TI - Surgical management of bleeding peptic ulcer. PMID- 20294684 TI - The diagnosis and treatment of early conductive deafness. PMID- 20294685 TI - The scope of psychiatry. PMID- 20294686 TI - FIRST ANNUAL REPORT of the Rehabilitation Department Leahi Hospital, June 30, 1946. PMID- 20294687 TI - Thromboembolism. PMID- 20294688 TI - Tuberculosis, the shame of Illinois. PMID- 20294689 TI - Rapid treatment program for syphilis. PMID- 20294690 TI - Illinois hospital survey and plan progress report. PMID- 20294691 TI - Hysterectomy in a small general hospital. PMID- 20294692 TI - Epidemic diarrhea of the newborn (neonatal enteritis). PMID- 20294693 TI - Nitrous oxide, pen tothal anesthesia. PMID- 20294694 TI - X-ray therapy in non-malignant diseases. PMID- 20294695 TI - Tropical ulcer (Naga sore) in tea estate of Upper Assam. PMID- 20294696 TI - Antevenene in the treatment of black-water fever. PMID- 20294697 TI - An obstinate case of nausea and vomiting of pregnancy. PMID- 20294698 TI - Our food and economic aspect of nutrition. PMID- 20294699 TI - The place of biochemistry in medical education. PMID- 20294701 TI - Out postwar psychiatric programme. PMID- 20294700 TI - The problem of medical education and examination. PMID- 20294702 TI - Kerotodermia blennorrhagica. PMID- 20294703 TI - Post-war medical reconstruction. PMID- 20294704 TI - Oto-rhino-laryngology in post-war medical planning. PMID- 20294705 TI - Unusual changes in fibro-adenoma of the breast. PMID- 20294706 TI - The marrowgram in healthy Indians as studied by sternal puncture and smear preparations. PMID- 20294707 TI - Banti's syndrome. PMID- 20294708 TI - Acoustic neuroma. PMID- 20294709 TI - Current topics in anaesthetics. PMID- 20294710 TI - The trend of modern obstetrics. PMID- 20294711 TI - The surgical treatment of sciatica. PMID- 20294712 TI - A case of polyostotic fibrous dysplasia of bone. PMID- 20294713 TI - Use of bipp in appendicitis; report on 1,000 cases. PMID- 20294714 TI - Conditions affecting child health in Eire. PMID- 20294715 TI - End results in operative treatment for varicose veins. PMID- 20294716 TI - Retrospect and prospect in varicose vein surgery. PMID- 20294717 TI - The organization of ear, nose and throat work in Dublin. PMID- 20294718 TI - Some cases of ovarian malignancy. PMID- 20294719 TI - Surgical aspects of bronchogenic carcinoma. PMID- 20294720 TI - Roentgen therapy in cancer of the larynx. PMID- 20294721 TI - Surgical treatment of carcinoma of the larynx. PMID- 20294722 TI - Irradiation of hyperplastic lymphoid tissue in the nasopharynx. PMID- 20294723 TI - Supervoltage roentgen therapy of carcinoma of the esophagus. PMID- 20294724 TI - The diagnosis and management of spontaneous hypoglycemia. PMID- 20294725 TI - Tridione in the treatment of epilepsy. PMID- 20294726 TI - Spontaneous rupture of the spleen due to infectious mononucleosus. PMID- 20294727 TI - Report of the Committee on Audiovisual Aids. PMID- 20294728 TI - The basis for teaching social and environmental factors in medicine in the undergraduate medical curriculum. PMID- 20294730 TI - State funds in support of medical education. PMID- 20294729 TI - Some aspects of the clinical teaching of the social and environmental factors in medicine. PMID- 20294731 TI - The place of preventive medicine in the curriculum. PMID- 20294732 TI - The integration of teaching content and methods. PMID- 20294733 TI - Rationale of the medical treatment of essential hypertension. PMID- 20294734 TI - The role of the liver and B complex vitamins in estrogen metabolism. PMID- 20294735 TI - Heartburn of pregnancy. PMID- 20294736 TI - The relation of porphyrins to the etiology of cervical carcinoma. PMID- 20294737 TI - Aural discharges. PMID- 20294738 TI - Hypothyroidism and pregnancy. PMID- 20294739 TI - Some facts about cancer. PMID- 20294740 TI - Incidence of intestinal protozoa and parasites in routine stool examinations. PMID- 20294741 TI - The present state of health in the Punjab. PMID- 20294743 TI - Quackery. PMID- 20294742 TI - A plea for an Indian pharmacopoeia. PMID- 20294744 TI - Determination of sex. PMID- 20294745 TI - Neutrophilia in malaria. PMID- 20294746 TI - Transfusion of blood in ancient India. PMID- 20294747 TI - LAWS pertaining to malpractice. PMID- 20294748 TI - PHYSICIANS in court. PMID- 20294749 TI - NARCOTIC laws. PMID- 20294750 TI - The family physician in relation to vocational rehabilitation. PMID- 20294751 TI - STATUTES of Indiana regulating the practice of medicine. PMID- 20294752 TI - CARE of the insane. PMID- 20294753 TI - PHYSICIAN and the welfare acts. PMID- 20294754 TI - LEGAL aspects of autopsies. PMID- 20294755 TI - Federal income tax and the medical profession. PMID- 20294756 TI - National Foundation for Infantile Paralysis. PMID- 20294758 TI - INDIANA State Board of Health Organization, functions and services. PMID- 20294757 TI - LIST of presidents of the Indiana State Medical Association since its organization. PMID- 20294759 TI - PRINCIPLES of medical ethics of the American Medical Association. PMID- 20294760 TI - CONSTITUTION and by-laws of the Indiana State Medical Association. PMID- 20294761 TI - An outline for the study of strabismus cases. PMID- 20294762 TI - A report on industrial ophthalmology in Evansville, Indiana. PMID- 20294763 TI - The role of the contact lens in the conservation of vision. PMID- 20294764 TI - Acute iritis, including acute iridocyclitis and acute uveitis. PMID- 20294766 TI - The treatment of chronic suppurative otitis media. PMID- 20294765 TI - The use of penicillin locally in the eye. PMID- 20294767 TI - The doctor's role in public relations. PMID- 20294768 TI - Hemipelvectomy in the treatment of osteogenic sarcoma of the ilium. PMID- 20294769 TI - Preliminary report on transvaginal X-ray treatment of carcinoma of the cervix. PMID- 20294770 TI - Adhesive arachnoiditis following the intrathecal administration of penicillin. PMID- 20294771 TI - The use of caudal anesthesia in obstetrics. PMID- 20294772 TI - The doctor's role in the postwar world. PMID- 20294773 TI - [Renal insufficiency due to nephrocalcinosis of the infectious type]. PMID- 20294774 TI - Clinical biochemistry. PMID- 20294775 TI - Sarcomas of the soft parts. PMID- 20294776 TI - Chronic cystic disease (fibro-adenomatosis with extreme hyperplasia). PMID- 20294777 TI - Intraductal carcinoma of breast. PMID- 20294778 TI - Mixed tumor of sole of foot. PMID- 20294779 TI - Granular cell myoblastoma of the breast. PMID- 20294780 TI - A case of microaerophilic hemolytic streptococcus infection of a pilonidal dimple. PMID- 20294781 TI - Preliminary studies on the use of ionization in the treatment of hyperidrosis and bromidrosis. PMID- 20294782 TI - Contact dermatitis from shoes. PMID- 20294783 TI - The history of fungus diseases. PMID- 20294784 TI - Culture controlled treatment of gonorrhea with penicillin. PMID- 20294785 TI - The technique of diagnosis of breast carcinoma, the choice of treatment, and the criteria of inoperability. PMID- 20294786 TI - Infectious hepatitis; its etiology and management. PMID- 20294787 TI - The need for total rehabilitation of the tuberculous. PMID- 20294788 TI - Clinical and X-ray diagnosis of foot disorders. PMID- 20294789 TI - Streptomycin, its uses and abuses. PMID- 20294790 TI - Thiouracil. PMID- 20294791 TI - Practical aspects of allergy. PMID- 20294792 TI - Benadryl. PMID- 20294793 TI - Cirrhosis of the liver and liver therapy. PMID- 20294794 TI - Hospital pre-delivery care. PMID- 20294795 TI - [Not Available]. PMID- 20294796 TI - [Not Available]. PMID- 20294797 TI - [Not Available]. PMID- 20294799 TI - [Not Available]. PMID- 20294798 TI - [Not Available]. PMID- 20294800 TI - [Not Available]. PMID- 20294801 TI - [Not Available]. PMID- 20294802 TI - [Not Available]. PMID- 20294803 TI - [Not Available]. PMID- 20294804 TI - [Not Available]. PMID- 20294805 TI - [Not Available]. PMID- 20294806 TI - [Not Available]. PMID- 20294807 TI - [Not Available]. PMID- 20294808 TI - [Not Available]. PMID- 20294809 TI - [Not Available]. PMID- 20294810 TI - [Not Available]. PMID- 20294811 TI - [Not Available]. PMID- 20294812 TI - [Not Available]. PMID- 20294813 TI - [Not Available]. PMID- 20294814 TI - [Not Available]. PMID- 20294815 TI - [Not Available]. PMID- 20294816 TI - [Not Available]. PMID- 20294817 TI - [Not Available]. PMID- 20294818 TI - [Not Available]. PMID- 20294819 TI - [Not Available]. PMID- 20294820 TI - [Not Available]. PMID- 20294821 TI - [Not Available]. PMID- 20294822 TI - [Not Available]. PMID- 20294823 TI - [Not Available]. PMID- 20294824 TI - Outbreak of virus encephalomeningitis in north-west Middlesex. PMID- 20294825 TI - Continuous injection of penicillin; the Secunderabad apparatus. PMID- 20294826 TI - Mammary cysts and their treatment. PMID- 20294827 TI - Scrub-typhus vaccine; field trial in South-east Asia. PMID- 20294828 TI - Epilepsy and hysteria. PMID- 20294829 TI - Modification of human red cells by virus action; agglutination by incomplete Rh antibody. PMID- 20294830 TI - Dutch blood-transfusion service during the German occupation. PMID- 20294831 TI - Service psychiatry. PMID- 20294832 TI - PILLARS of health. PMID- 20294833 TI - Social pathology. PMID- 20294834 TI - Stevens-Johnson syndrome. PMID- 20294835 TI - Source of the red cells. PMID- 20294836 TI - Ascorbic-acid metabolism of Bantu soldiers. PMID- 20294837 TI - Recovery from starvation. PMID- 20294838 TI - Folic acid in the treatment of the sprue syndrome. PMID- 20294839 TI - Care of the urinary tract in paraplegic patients; review of 82 cases. PMID- 20294840 TI - Bilateral congenital dislocation of radial head. PMID- 20294841 TI - Use of a tourniquet to prolong the effect of penicillin. PMID- 20294842 TI - Screening-out the neurotic. PMID- 20294843 TI - The home consultant. PMID- 20294844 TI - Haemolytic disease of the newborn. PMID- 20294845 TI - Experimental tumorigenesis. PMID- 20294846 TI - Revaccination in adults. PMID- 20294847 TI - Sand-fly fever. PMID- 20294848 TI - Estimation of penicillin in serum. PMID- 20294849 TI - Ankylosing spondylitis and fluorosis. PMID- 20294850 TI - The Rh factor in hemolytic disease of the newborn. PMID- 20294851 TI - The moral aspects of the Rh factor. PMID- 20294852 TI - Moral aspects of artificial insemination. PMID- 20294854 TI - Nicotine reviewed. PMID- 20294853 TI - The diagnosis of two congenital heart lesions amenable to surgery. PMID- 20294855 TI - Incidence and etiology of postpartum hemorrhage. PMID- 20294856 TI - Benadryl. PMID- 20294857 TI - The nutrition of the fetus. PMID- 20294858 TI - Modern trends in vascular surgery. PMID- 20294859 TI - Singultus (hiccough). PMID- 20294860 TI - Studies of pneumonias in childhood. PMID- 20294861 TI - Obligation of the physician to psychiatry. PMID- 20294862 TI - Diathermy machines. PMID- 20294863 TI - Intracranial cholesteatoma, epidermoid or pearly tumor; report of a case. PMID- 20294864 TI - [Rupture of an aneurysm of the thoracic aorta with left hemothorax]. PMID- 20294865 TI - The treatment of rheumatoid and infective arthritis by the sulphonamides, with special reference to proseptasine, sulphadiazine and sulphaguanidine. PMID- 20294866 TI - The physiological basis of modern anaesthesia. PMID- 20294867 TI - Uterine chorionepithelioma with severe intraperitoneal haemorrhage. PMID- 20294868 TI - Intravenous administration of oxygen. PMID- 20294869 TI - Charcot's disease of the hip. PMID- 20294870 TI - [Not Available]. PMID- 20294871 TI - [Not Available]. PMID- 20294872 TI - [Not Available]. PMID- 20294873 TI - [Not Available]. PMID- 20294874 TI - [Not Available]. PMID- 20294875 TI - [Not Available]. PMID- 20294876 TI - [Not Available]. PMID- 20294877 TI - [Not Available]. PMID- 20294878 TI - [Not Available]. PMID- 20294879 TI - [Not Available]. PMID- 20294880 TI - [Not Available]. PMID- 20294881 TI - [Not Available]. PMID- 20294882 TI - [Not Available]. PMID- 20294883 TI - [Not Available]. PMID- 20294884 TI - [Not Available]. PMID- 20294886 TI - [Not Available]. PMID- 20294885 TI - [Not Available]. PMID- 20294887 TI - [Not Available]. PMID- 20294888 TI - [Not Available]. PMID- 20294889 TI - [Not Available]. PMID- 20294890 TI - [Not Available]. PMID- 20294891 TI - [Not Available]. PMID- 20294892 TI - [Not Available]. PMID- 20294893 TI - [Not Available]. PMID- 20294894 TI - [Not Available]. PMID- 20294895 TI - [Not Available]. PMID- 20294896 TI - [Not Available]. PMID- 20294897 TI - [Not Available]. PMID- 20294898 TI - [Not Available]. PMID- 20294899 TI - [Not Available]. PMID- 20294900 TI - [Not Available]. PMID- 20294901 TI - [Not Available]. PMID- 20294902 TI - [Not Available]. PMID- 20294903 TI - [Not Available]. PMID- 20294904 TI - [Not Available]. PMID- 20294905 TI - [Not Available]. PMID- 20294906 TI - [Not Available]. PMID- 20294907 TI - [Not Available]. PMID- 20294908 TI - [Not Available]. PMID- 20294909 TI - [Not Available]. PMID- 20294910 TI - [Not Available]. PMID- 20294911 TI - [Not Available]. PMID- 20294912 TI - [Not Available]. PMID- 20294913 TI - [Not Available]. PMID- 20294914 TI - [Not Available]. PMID- 20294915 TI - [Not Available]. PMID- 20294916 TI - [Not Available]. PMID- 20294917 TI - [Not Available]. PMID- 20294918 TI - [Not Available]. PMID- 20294919 TI - [Not Available]. PMID- 20294920 TI - [Not Available]. PMID- 20294921 TI - [Not Available]. PMID- 20294922 TI - [Not Available]. PMID- 20294923 TI - [Not Available]. PMID- 20294924 TI - [Not Available]. PMID- 20294925 TI - [Not Available]. PMID- 20294926 TI - [Not Available]. PMID- 20294927 TI - [Not Available]. PMID- 20294928 TI - [Not Available]. PMID- 20294929 TI - [Not Available]. PMID- 20294930 TI - [Not Available]. PMID- 20294931 TI - [Not Available]. PMID- 20294932 TI - [Not Available]. PMID- 20294934 TI - [Not Available]. PMID- 20294933 TI - [Not Available]. PMID- 20294935 TI - [Not Available]. PMID- 20294936 TI - [Not Available]. PMID- 20294937 TI - [Not Available]. PMID- 20294938 TI - [Not Available]. PMID- 20294939 TI - [Not Available]. PMID- 20294940 TI - [Not Available]. PMID- 20294941 TI - [Not Available]. PMID- 20294942 TI - [Not Available]. PMID- 20294943 TI - [Not Available]. PMID- 20294944 TI - [Not Available]. PMID- 20294945 TI - [Not Available]. PMID- 20294947 TI - [Not Available]. PMID- 20294946 TI - [Not Available]. PMID- 20294948 TI - [Not Available]. PMID- 20294949 TI - [Not Available]. PMID- 20294950 TI - [Not Available]. PMID- 20294951 TI - [Not Available]. PMID- 20294952 TI - [Not Available]. PMID- 20294953 TI - [Not Available]. PMID- 20294954 TI - [Not Available]. PMID- 20294955 TI - [Not Available]. PMID- 20294956 TI - [Not Available]. PMID- 20294957 TI - [Not Available]. PMID- 20294958 TI - [Not Available]. PMID- 20294959 TI - [Not Available]. PMID- 20294960 TI - [Not Available]. PMID- 20294961 TI - [Not Available]. PMID- 20294962 TI - [Not Available]. PMID- 20294963 TI - Managing the glaucomatous patient. PMID- 20294964 TI - Urethritis in the male; an analysis of 205 cases and a review of the American literature on this subject. PMID- 20294965 TI - The possibilities and limitations of the fenestration operation for otosclerosis. PMID- 20294966 TI - Carcinoma of the cervix. PMID- 20294967 TI - Tophaceous gout; a case report. PMID- 20294968 TI - THE first medical journal and some of its progeny. PMID- 20294969 TI - The evolution of inguinal hernia surgery. PMID- 20294970 TI - Search and research. PMID- 20294971 TI - VITAMINS in the practice of surgery. PMID- 20294972 TI - Fungous disease therapy. PMID- 20294973 TI - Degenerative disease associated with age. PMID- 20294975 TI - The evolution of inguinal hernial surgery. PMID- 20294974 TI - The use of a rubber insert in dacryocystorhinostomy. PMID- 20294976 TI - Notable contributors to our knowledge of syphilis. PMID- 20294977 TI - Positive convalescence. PMID- 20294978 TI - The diagnosis and management of some common disorders in infancy. PMID- 20294980 TI - Some conditions which give rise to running ears met with in general practice. PMID- 20294979 TI - The prostate, the urethro-trigonal and the vagino-cervical regions in relation to local and general symptoms. PMID- 20294981 TI - The topical diagnosis of pyuria or hematuria. PMID- 20294982 TI - Can doctors strike? PMID- 20294983 TI - A consideration of vaccination against influenza. PMID- 20294984 TI - Migration and the population potential of monsoon Asia. PMID- 20294985 TI - Future migration into Latin America. PMID- 20294986 TI - Social and psychological factors affecting fertility; the planning of fertility. PMID- 20294988 TI - Voluntary prepayment medical care and its rural aspects. PMID- 20294987 TI - Medical service program in the Veterans Administration hospitals. PMID- 20294989 TI - The treatment of persons who have bronchial asthma. PMID- 20294990 TI - Nitrogen balance and its clinical application. PMID- 20294991 TI - Observations on the management of vasomotor rhinitis. PMID- 20294992 TI - Orchiectomy and hormones in prostatic carcinoma. PMID- 20294993 TI - Mycetoma or Madura foot; report of cases including one case of maduromycosis of the hand. PMID- 20294994 TI - Intestinal ascaris diagnosed roentgenographically in Minnesota. PMID- 20294995 TI - Meniere's disease; endolymphatic hydrops. PMID- 20294996 TI - Peripheral arterial embolism. PMID- 20294997 TI - The value of imponderables. PMID- 20294998 TI - The hospital, a look ahead; some aspects of clinical investigation. PMID- 20294999 TI - Atelectasis as a factor in the medical treatment of pleural empyema; the necessity of combating atelectasis by remedial breathing exercises. PMID- 20295000 TI - Electrocardiography. PMID- 20295001 TI - [Ewing tumor of fibula]. PMID- 20295002 TI - [Acute and chronic salpingo-oophoritis]. PMID- 20295003 TI - Streptomycin treatment of pulmonary infections; clinical and bacteriologic studies of six cases. PMID- 20295004 TI - Sensitivity to pork-liver extract in pernicious anemia; clinical observations on 14 patients. PMID- 20295005 TI - The Commonwealth's health program. PMID- 20295006 TI - Urology. PMID- 20295007 TI - [Multiple polypoid carcinomas of stomach, with metastasis]. PMID- 20295008 TI - [Adenocarcinoma of pancreas, with liver metastasis]. PMID- 20295009 TI - Human laboratory infection with Venezuelan equine encephalomyelitis virus; report of four cases. PMID- 20295010 TI - A survey of the first three months of operation of a Veterans Administration mental hygiene clinic. PMID- 20295011 TI - Creeping eruption in New England; a report of two cases. PMID- 20295012 TI - Surgery of the autonomic nervous system. PMID- 20295013 TI - [Periarteritis nodosa]. PMID- 20295014 TI - [Congenital tracheobronchial cyst of esophageal wall]. PMID- 20295015 TI - Physical medicine in traumatic injuries. PMID- 20295016 TI - Physical therapy in the treatment of arthritis. PMID- 20295017 TI - The place of physical medicine in the treatment of patients with mental conditions. PMID- 20295018 TI - Comments on Army radiology in World War II. PMID- 20295019 TI - Pediatric approach to the management of asthma in childhood. PMID- 20295020 TI - The possibility of preventing breast cancer in women; is artificial feeding of infants justified? PMID- 20295021 TI - An anthropologist looks at American Indian medicine. PMID- 20295022 TI - Medicine in New York folklore. PMID- 20295023 TI - Is general practice becoming a specialty? PMID- 20295024 TI - Pilonidal (sacrococcygeal) cyst and sinus; an evaluation of some of the recently proposed therapeutic measures. PMID- 20295025 TI - On the use of a medicament to reduce the appetite in the treatment of obesity and other conditions. PMID- 20295026 TI - Office procedure in applying penicillin therapy to acute suppurative bartholinitis. PMID- 20295027 TI - Pathogenesis of spina bifida and related congenital malformations. PMID- 20295028 TI - The symptomatic treatment of hay fever with diaminobenzopyridyl HCl (N'-pyridyl N'-benzyl-N-dimethylethylenediamine hydrochloride)(pyribenzamine). PMID- 20295029 TI - The nitrogen mustards and their application in neoplastic diseases. PMID- 20295030 TI - Pentothal nitrous-oxide oxygen anesthesia. PMID- 20295031 TI - Coexistence of malformations of the genital and urinary tracts in women. PMID- 20295032 TI - Amphetamine sulfate (benzedrine) in the treatment of obesity; a critical estimate. PMID- 20295033 TI - Benzedrine sulfate in elderly people. PMID- 20295034 TI - Treatment of hepatic insufficiency. PMID- 20295035 TI - Neurologic complications following the administration of pertussis vaccine. PMID- 20295036 TI - Giant cell tumor of the patella treated by resection. PMID- 20295037 TI - Early localization with the use of pantopaque of an acute epidural spinal abscess. PMID- 20295038 TI - PUBLIC medical care. PMID- 20295039 TI - Compound fractures. PMID- 20295040 TI - Clinical manifestations of syphilis. PMID- 20295041 TI - Ankylostomiasis. PMID- 20295042 TI - Nasal physiology in dietary deficiency. PMID- 20295043 TI - Management of cervicovaginal disorders. PMID- 20295044 TI - The absorbable sponge as a hemostatic agent. PMID- 20295045 TI - Principal causes of maternal deaths in Nebraska, 1940-1945. PMID- 20295046 TI - Spherocytosis and increased erythrocyte fragility in four generations of the family of a patient with congenital hemolytic anemia. PMID- 20295047 TI - Amebiasis; case reports from the North Carolina Baptist Hospital. PMID- 20295048 TI - Peptic ulcer of the duodenum; a review of 98 cases treated surgically. PMID- 20295049 TI - The treatment of meningitis in childhood; with particular reference to the use of penicillin and streptomycin. PMID- 20295050 TI - Regional enteritis with observations concerning its pathogenesis. PMID- 20295051 TI - The use of BAL in the treatment of heavy-metal poisoning. PMID- 20295052 TI - Special disabilities in children with organic brain pathology. PMID- 20295053 TI - Basis for therapy in shock. PMID- 20295054 TI - Renal tumors. PMID- 20295055 TI - Hemorrhage in the last trimester of pregnancy. PMID- 20295057 TI - West River medical doctors. PMID- 20295056 TI - METOPON hydrochloride (methyldihydromorphinone hydrochloride). PMID- 20295058 TI - Canadian research in aviation medicine. PMID- 20295059 TI - Portal cirrhosis. PMID- 20295060 TI - Can military medical education offer anyfeatures applicable to civilian professional instruction? PMID- 20295061 TI - Treatment of the uterine prolapse syndrome by the Spalding-Richardson composite procedure. PMID- 20295062 TI - Non-syphilitic lesions of the penis. PMID- 20295063 TI - Penicillin, indications and methods of administration. PMID- 20295064 TI - Readjustment of the handicapped veteran. PMID- 20295065 TI - Rural health services; a challenge to the county medical society. PMID- 20295066 TI - Ambrose Bierce and his warped personality. PMID- 20295068 TI - Eyestrain. PMID- 20295067 TI - The doctor's problem with alcoholics. PMID- 20295069 TI - Cataract. PMID- 20295070 TI - Infections of the eye. PMID- 20295071 TI - The treatment of intraocular foreign bodies. PMID- 20295072 TI - Contact lenses. PMID- 20295073 TI - Mydriatics; some developments. PMID- 20295075 TI - The hysteric in general practice. PMID- 20295074 TI - Serum phosphatases and their significance. PMID- 20295076 TI - Pain and its problems; pain in respiratory disease. PMID- 20295077 TI - Purpura. PMID- 20295078 TI - The xanthine diuretics. PMID- 20295079 TI - Interpretive morphology. PMID- 20295080 TI - Experimental hypertension. PMID- 20295081 TI - Hypertension. PMID- 20295083 TI - Visceral leishmaniasis. PMID- 20295082 TI - The centennial of ether anesthesia. PMID- 20295084 TI - Sudden nerve deafness; treatment by the intravenous administration of histamine. PMID- 20295085 TI - Total excision of scapula for osteochondroma; report of case. PMID- 20295086 TI - Medical aspects of malignant lesions of the anus, rectum and colon. PMID- 20295087 TI - Inflammatory diseases of the bowel. PMID- 20295088 TI - Report of genito-urinary surgery for 1945. PMID- 20295089 TI - Myasthenia gravis. PMID- 20295090 TI - Two cases of lupus erythematosus disseminata. PMID- 20295091 TI - Carcinoma of lung treated by total left pneumonectomy. PMID- 20295092 TI - Case of frost bite; loss of all toes. PMID- 20295093 TI - Septic arthritis of the hip. PMID- 20295094 TI - Case of peculiar blood dyscrasia. PMID- 20295095 TI - Saints, animals, the stars and demons in mediaeval medicine. PMID- 20295096 TI - Special techniques for unusual fractures of the forearm. PMID- 20295097 TI - Bilateral calcification of the vasa deferentia. PMID- 20295098 TI - Work at high altitude; plan of study and methods. PMID- 20295099 TI - The surgical management of irradiation injuries. PMID- 20295100 TI - A consideration of the antierythrocytic factors in resistance to malaria. PMID- 20295101 TI - Report of a case of land-mine wound. PMID- 20295102 TI - The effect of foliandrin on the cardio-inhibitory center of the medulla. PMID- 20295103 TI - Benjamin Rush, venesectionist. PMID- 20295104 TI - Historical notes on the Twelfth General Hospital (U.S.) February 15, 1942 to September 15, 1945; the Twelfth General Hospital in Ain-el-Turck and Naples. PMID- 20295105 TI - Early medical books in the Archibald Church Library; cardiology. PMID- 20295106 TI - Xeroderma pigmentosum. PMID- 20295107 TI - Medicine in the time of the Crusades. PMID- 20295108 TI - Water pollution control. PMID- 20295110 TI - Pollinosis in South Africa; a study of seasonal hay-fever. PMID- 20295109 TI - HEALTH maintenance clinic for cancer prevention at the Pawtucket Memorial Hospital. PMID- 20295111 TI - Responsibilities of the practitioner in civil aviation in South Africa. PMID- 20295112 TI - Central nervous system manifestations of glandular fever. PMID- 20295113 TI - Typhus fever in the eastern Transvaal, with special reference to an epidemic occurring in 1945. PMID- 20295114 TI - Reports of four interesting cases treated at 110. Military Hospital over the last 18 months. PMID- 20295115 TI - Carotid body tumour with invasion of the cerebello-pontine angle. PMID- 20295116 TI - Prostatitis and vesiculitis; syndromes associated with chronic non-venereal pathology. PMID- 20295117 TI - Diploma in anaesthesia. PMID- 20295118 TI - SOAP for battling disease. PMID- 20295119 TI - Planigraphy in the diagnosis of bronchogenic carcinoma. PMID- 20295120 TI - [Not Available]. PMID- 20295121 TI - [Not Available]. PMID- 20295122 TI - [Not Available]. PMID- 20295123 TI - [Not Available]. PMID- 20295124 TI - [Not Available]. PMID- 20295125 TI - [Not Available]. PMID- 20295126 TI - [Not Available]. PMID- 20295127 TI - [Not Available]. PMID- 20295128 TI - [Not Available]. PMID- 20295129 TI - [Not Available]. PMID- 20295130 TI - [Not Available]. PMID- 20295131 TI - [Not Available]. PMID- 20295132 TI - [Not Available]. PMID- 20295133 TI - [Not Available]. PMID- 20295134 TI - The purpuric diseases. PMID- 20295135 TI - A medical student in the land of Hearne and Kelsey. PMID- 20295136 TI - Causation in pathology. PMID- 20295137 TI - The pharmacology of digitalis. PMID- 20295138 TI - Pulmonary tuberculosis and the general practitioner. PMID- 20295139 TI - Carcinoma of the caecum and of the left colon. PMID- 20295140 TI - Surgical therapy of duodenal ulcer. PMID- 20295141 TI - The evolution of surgical procedures in biliary disease. PMID- 20295142 TI - Symposium on heart disease. PMID- 20295143 TI - Nutrition in relation to complications in pregnancy. PMID- 20295144 TI - Neuro-surgical procedures for everyday practice. PMID- 20295145 TI - [Not Available]. PMID- 20295146 TI - [Not Available]. PMID- 20295147 TI - [Not Available]. PMID- 20295148 TI - [Not Available]. PMID- 20295149 TI - [Not Available]. PMID- 20295150 TI - [Not Available]. PMID- 20295151 TI - [Not Available]. PMID- 20295152 TI - [Not Available]. PMID- 20295153 TI - [Not Available]. PMID- 20295154 TI - [Not Available]. PMID- 20295155 TI - [Not Available]. PMID- 20295156 TI - [Not Available]. PMID- 20295157 TI - [Not Available]. PMID- 20295158 TI - Venereal disease education. PMID- 20295159 TI - Molded plaster slabs. PMID- 20295160 TI - NURSING Service during the years 1939-1945. PMID- 20295161 TI - EXPERIENCES with a field dressing station Northwest Europe. PMID- 20295163 TI - Nutrition. PMID- 20295162 TI - NURSING service in a C. C. S. in England and North-west Europe. PMID- 20295164 TI - Histamine cephalgia with report of two cases. PMID- 20295165 TI - The place and value of physiotherapy departments in the R.C.A.M.C. PMID- 20295166 TI - The Royal Canadian Naval Nursing Service. PMID- 20295167 TI - Venereal disease control in the United States occupied zone of Germany. PMID- 20295168 TI - Some phases of fracture treatment. PMID- 20295169 TI - The flight surgeon; his role in student pilot training. PMID- 20295170 TI - Army veterinary inspection of foods of animal origin. PMID- 20295171 TI - The Navy's plastic ocular restoration. PMID- 20295172 TI - A sanitary engineer views the post-war world. PMID- 20295173 TI - Medical Administrative Corps officers in the chain of evacuation. PMID- 20295174 TI - Nursing on hospital ships. PMID- 20295175 TI - Nursing service for veterans. PMID- 20295176 TI - Relation, historical and surgical, of the expedition of the Army of the Orient in Egypt and in Syria [transl. Rose Alexander]. PMID- 20295177 TI - Secondary colonies of bacteria induced by salts of alkali metals, with special reference to Chromobacterium violaceum and other bacteria on lithium chloride agar. PMID- 20295178 TI - Studies of freshwater red algae. PMID- 20295179 TI - The influence of pH and certain growth factors on mycelial growth and perithecial formation by Sordaria fimicola. PMID- 20295180 TI - Chromosome numbers in the Myrtaceae. PMID- 20295181 TI - Antimony trichloride ethanol precipitation for the fluorometric determination of riboflavin in pork. PMID- 20295182 TI - Preservation of eggs; effect of various oils and oiling temperatures on the keeping quality of shell eggs stored at 70 degrees F. and 30 degrees F. PMID- 20295183 TI - Dried whole egg powder; some factors affecting colour. PMID- 20295184 TI - Dried whole egg powder; further studies on the effect of added substances. PMID- 20295185 TI - Dried whole egg powder; some observations on the quality of powder prepared from frozen, liquid egg. PMID- 20295186 TI - Production and properties of 2,3-butanediol; influence of the inoculum on the Aerobacillus polymyxa fermentation. PMID- 20295188 TI - [Not Available]. PMID- 20295187 TI - The solvent extraction of crude mustard gas. PMID- 20295189 TI - [Not Available]. PMID- 20295190 TI - [Not Available]. PMID- 20295191 TI - The bromination of saturated 3-ketosteroids with N-bromoimides. PMID- 20295192 TI - [Not Available]. PMID- 20295193 TI - [Not Available]. PMID- 20295194 TI - [Not Available]. PMID- 20295195 TI - [Not Available]. PMID- 20295196 TI - [Not Available]. PMID- 20295197 TI - [Not Available]. PMID- 20295198 TI - [Not Available]. PMID- 20295199 TI - [Not Available]. PMID- 20295200 TI - The influence of dyes on the respiration of baker's yeast. PMID- 20295201 TI - [Not Available]. PMID- 20295202 TI - [Not Available]. PMID- 20295203 TI - The blood picture of normal laboratory animals; a review of the literature 1936 1946. PMID- 20295204 TI - Carrier-distillation method for spectrographic analysis and its application to the analysis of uranium-base materials. PMID- 20295205 TI - Study of Ofner's method for the determination of invert sugar. PMID- 20295206 TI - Observation of copulation in Amphiuma tridactylum. PMID- 20295207 TI - The path of science [Bk Rev.]. PMID- 20295209 TI - HISTORY and work of the Palaeontographical Society. PMID- 20295208 TI - Atmospheric oscillations. PMID- 20295210 TI - Spread of discharge in Geiger counters. PMID- 20295211 TI - Preparation of thin specimen films. PMID- 20295212 TI - Inhibition of catechol bacteriostasis by molybdates. PMID- 20295213 TI - Succinic dehydrogenase in Protozoa. PMID- 20295214 TI - Co-existence of two different esterases in liver juice. PMID- 20295215 TI - Changes in the electrophoretic pattern of the cow's milk during early lactation. PMID- 20295216 TI - Australopithecinae or Dartians. PMID- 20295217 TI - DEFECTIVE colour vision in industry. PMID- 20295218 TI - Plant carbonic anhydrase. PMID- 20295219 TI - Elaboration of hydrochloric acid by gastric mucosa. PMID- 20295220 TI - Serum chlorides in pregnant mice. PMID- 20295221 TI - Microdetermination of copper in biological substances. PMID- 20295222 TI - Gamma-radiation from polonium and from lithium bombarded with alpha-particles. PMID- 20295223 TI - Interaction of fast neutrons with beryllium and aluminium. PMID- 20295224 TI - Action of mustard gas (beta beta'-dichlorethylsulphide) on thiol groups of proteins. PMID- 20295225 TI - Psychologists in the Association of Scientific Workers. PMID- 20295226 TI - Toxic organo-lead compounds. PMID- 20295227 TI - Social medicine and social pathology. PMID- 20295228 TI - Plasma cellular reaction and its relation to the formation of antibodies in vitro. PMID- 20295229 TI - Use of seeds in the insect transmission of some plant viruses. PMID- 20295230 TI - Entamoeba sp. from the Syrian hamster (Cricetus auratus). PMID- 20295231 TI - Tumour inhibition with extracts of urine. PMID- 20295232 TI - A possible explanation of the relations between hereditary anaemias and depigmentation in the mouse. PMID- 20295233 TI - Relation of the thyroid to infections. PMID- 20295234 TI - Chemical composition of Egyptian cow's milk in relation to milk laws. PMID- 20295235 TI - Structures of ethylene oxide and cyclopropane. PMID- 20295237 TI - A proposed test for sterilized milk. PMID- 20295236 TI - Action of phosphorus pentachloride on p-sulphonamido benzoic acid. PMID- 20295238 TI - SCIENCE and the real freedoms. PMID- 20295239 TI - Hereditary (seed-borne) symbiosis in Casuarina equisetifolia Forst. PMID- 20295240 TI - Scientific equipment in Europe; present needs. PMID- 20295241 TI - Peat, hay-fever and pharmacognosy. PMID- 20295242 TI - Progress of cancer research. PMID- 20295243 TI - Structure of fibrous keratin. PMID- 20295244 TI - Incipient shrinkage of collagen and gelatin. PMID- 20295245 TI - Control of low-temperature injury in the Victoria plum. PMID- 20295246 TI - A morphological change induced in leaves of Theobroma cacao by mineral deficiency. PMID- 20295247 TI - Mechanism of hydrogen peroxide formation by spermatozoa and the role of amino acids in sperm motility. PMID- 20295248 TI - Acanthocephala of trout and anthelminthics; behavior in vitro. PMID- 20295249 TI - Criteria of hybridity. PMID- 20295250 TI - PROCEEDINGS of the Pan-African congress of prehistory. PMID- 20295251 TI - A new polarograph. PMID- 20295252 TI - Effect of phase displacement between the inducing and guiding fields in a betatron. PMID- 20295253 TI - Longevity and casualties among naturalists in tropical America. PMID- 20295254 TI - A biophysics symposium. PMID- 20295255 TI - Field theory in biology. PMID- 20295256 TI - Particle and field concepts in biology. PMID- 20295257 TI - Okinawa and its people. PMID- 20295259 TI - The selection and training of future scientists. PMID- 20295258 TI - The interrelationships of enzymes, vitamins and hormones. PMID- 20295260 TI - Microbiology in the USSR in 1946. PMID- 20295261 TI - Aptitude testing. PMID- 20295262 TI - The production and ripening of red blood cells. PMID- 20295263 TI - The story of two atoms. PMID- 20295264 TI - The weapons of panacea. PMID- 20295265 TI - The origin of life. PMID- 20295266 TI - Review and progress in neurologic problems. PMID- 20295267 TI - Prefrontal lobotomy or leucotomy. PMID- 20295268 TI - Schizophrenia in childhood; its modification by prefrontal lobotomy. PMID- 20295270 TI - Psychiatric lessons from World War II. PMID- 20295269 TI - Psychiatric experiences in the war, 1941-1946. PMID- 20295272 TI - Psychiatry in prospect. PMID- 20295271 TI - Accomplishments of psychiatry in the Army Air Forces. PMID- 20295273 TI - Psychiatric casualties in submarine warfare. PMID- 20295274 TI - The paranoiac officer and the officer paranee. PMID- 20295275 TI - Pragmatic psychotherapy in military training centers. PMID- 20295276 TI - The use of hypnosis in the treatment of acute combat reactions. PMID- 20295277 TI - Experience with group psychotherapy as a method of treatment for veterans. PMID- 20295278 TI - The utilization of a therapy group in teaching psychotherapy. PMID- 20295279 TI - The use of private patients for psychiatric teaching in a medical school. PMID- 20295280 TI - Psychotherapy for the general practitioner; a program for training; post-graduate education. PMID- 20295281 TI - The homosexual woman. PMID- 20295282 TI - The use of electric shock therapy in psychoneurosis. PMID- 20295283 TI - An evaluation of shock therapy. PMID- 20295284 TI - Effects of electrically induced convulsions upon respiration in man. PMID- 20295285 TI - A program for training attendants in mental hospitals. PMID- 20295287 TI - Emotions in the allergic individual. PMID- 20295286 TI - Brain metabolism in man; unanesthetized and in pentothal narcosis. PMID- 20295288 TI - Psychological factors in men with peptic ulcers. PMID- 20295289 TI - The psychiatric resources of New York. PMID- 20295290 TI - Principles of psychotherapy in latent schizophrenia. PMID- 20295291 TI - Concealment of facts in psycho analysis. PMID- 20295292 TI - Motives in the trauma of weaning. PMID- 20295293 TI - Training in remedial reading and psychotherapy. PMID- 20295294 TI - Medico-legal report on a deserter. PMID- 20295295 TI - A semi-obsession a deux. PMID- 20295296 TI - The psychogenesis of fugue states. PMID- 20295297 TI - Psychiatry and psychology. PMID- 20295298 TI - Newer genetic investigations on impotence and frigidity. PMID- 20295299 TI - Alterations in the state of the ego in hypnosis. PMID- 20295300 TI - Analysis of an unusual case of fetishism. PMID- 20295301 TI - Review of some fundamental considerations in psychotherapy. PMID- 20295302 TI - Atropine premedication in electro shock therapy. PMID- 20295303 TI - Prefrontal lobotomy in the treatment of schizophrenia. PMID- 20295304 TI - Reflections on the state of psychiatry in the realm of medicine. PMID- 20295305 TI - Proposal for creation of small, urbanly located state hospitals. PMID- 20295306 TI - Asymmetry in occipital electroencephalograms. PMID- 20295307 TI - Relationship of psychiatry to problems of medical care. PMID- 20295308 TI - Histamine treatment of cerebral arteriosclerosis. PMID- 20295309 TI - Magical thinking and ritual to preserve omnipotence as demonstrated in cases of compulsion neurosis. PMID- 20295310 TI - [Multiple sclerosis]. PMID- 20295311 TI - Group psychotherapy. PMID- 20295312 TI - [Not Available]. PMID- 20295313 TI - [Not Available]. PMID- 20295314 TI - Dystrophia myotonica as a generalized disease. PMID- 20295315 TI - [Not Available]. PMID- 20295316 TI - [Not Available]. PMID- 20295317 TI - The innervation and actions of the neuro-hypophysis; an investigation using the method of remote-control stimulation. PMID- 20295318 TI - Trends in industrial nursing. PMID- 20295319 TI - Medical records. PMID- 20295320 TI - The visiting nurse in industry. PMID- 20295321 TI - How the nurse in industry contributes to the plant safety and health program; treatment in injury and illness. PMID- 20295322 TI - Midwifery training in Italy. PMID- 20295323 TI - Cancer of the oesophagus and its modern treatment. PMID- 20295324 TI - Urine testing. PMID- 20295325 TI - Restoration of normal movement after operation and confinement. PMID- 20295326 TI - Penicillin and sulphonamides used in the treatment of pneumococcal meningitis. PMID- 20295327 TI - Restoration of normal movement after operation and confinement. PMID- 20295328 TI - Tropical diseases; amoebiasis and amoebic dysentery. PMID- 20295329 TI - Surgery of the eye; plastic surgery, squint, lacrimal obstruction. PMID- 20295330 TI - Acute carcinoma of pregnancy. PMID- 20295331 TI - Early ambulation and other modern methods in surgical care. PMID- 20295332 TI - UNIVERSITY degree in nursing. PMID- 20295333 TI - New hope for lepers lepers and leprosy through the centuries. PMID- 20295334 TI - Insurance for nurses. PMID- 20295335 TI - New methods of treating frostbite. PMID- 20295337 TI - Diabetes, 1947. PMID- 20295338 TI - The preservation of bacterial cultures for classroom use. PMID- 20295336 TI - A half century of progress in brain surgery. PMID- 20295339 TI - Psychosomatic medicine and tuberculosis. PMID- 20295340 TI - Nursing care of the schizophrenic. PMID- 20295341 TI - Surgery of the spinal cord; special emphasis on the nursing care pre-operatively and post-operatively. PMID- 20295342 TI - British reactions to the national health insurance scheme. PMID- 20295343 TI - Ocular complications of Sydenham's chorea; a case report. PMID- 20295344 TI - The vectoluminator and vectometer as a new medium for visual training. PMID- 20295345 TI - Facts to remember about cataract lenses. PMID- 20295346 TI - A hollow cathode source applicable to spectrographic analysis for the halogens and gases. PMID- 20295347 TI - High transmission windows for radiation of 3 to 14 microns wave-length. PMID- 20295348 TI - Photographic granularity and graininess; some characteristics of the visual system of importance in the evaluation of graininess and granularity. PMID- 20295349 TI - A method for making precise resolution measurements. PMID- 20295350 TI - The production and calibration of Foucault test objects of various contrasts. PMID- 20295351 TI - The Stiles and Crawford effect in polarized light. PMID- 20295352 TI - Spectrochemical analysis by the copper spark method. PMID- 20295353 TI - A method for measuring the spectral energy distribution of low brightness light sources. PMID- 20295354 TI - Notes on W. S. Stiles' paper entitled, A modified Helmholtz line-element in brightness-colour space. PMID- 20295355 TI - An infra-red prism spectrometer of high resolving power. PMID- 20295356 TI - Note on the number of distinct chromaticities. PMID- 20295357 TI - Anomalies of the ocular muscles. PMID- 20295358 TI - Strabismus. PMID- 20295359 TI - Eliminating visible crescents in contact lenses. PMID- 20295360 TI - Color vision and color blindness; a mechanism in terms of modern evidence. PMID- 20295361 TI - Alternating squint. PMID- 20295362 TI - Applying psychology to patient-personality. PMID- 20295363 TI - Athol's industrial screening test. PMID- 20295365 TI - Clinical orthoptic procedure: paralytic squint. PMID- 20295364 TI - Visual training, the optometrist's birthright. PMID- 20295366 TI - Myopia, a theory and approach for research. PMID- 20295367 TI - Paralytic squint. PMID- 20295368 TI - Two unusual artificial eye cases. PMID- 20295369 TI - Binocular poise; its significance in the symptomatology, diagnosis and treatment of binocular anomalies. PMID- 20295370 TI - Amateur opticians in Switzerland. PMID- 20295371 TI - Optometry. PMID- 20295372 TI - Educating the partially sighted child. PMID- 20295373 TI - Distant and near retinoscopy and their relationship. PMID- 20295374 TI - Ocular headache. PMID- 20295375 TI - Retinoscopy; the influence of instrument design. PMID- 20295376 TI - The dynamic retinoscopy controversy. PMID- 20295378 TI - Care and treatment of contact lenses. PMID- 20295377 TI - Visual psychology. PMID- 20295379 TI - Orthoptics in Great Britain. PMID- 20295380 TI - Some thoughts on visual training. PMID- 20295381 TI - The cauldron boils. PMID- 20295382 TI - Statistics of the blind. PMID- 20295383 TI - International health activities and the part of the voluntary agency. PMID- 20295384 TI - Congenital cataract associated with German measles. PMID- 20295385 TI - Meeting the need for nurses in sight conservation. PMID- 20295386 TI - The effectiveness of the services rendered by the Glaucoma Clinic of the Illinois Eye and Ear Infirmary. PMID- 20295387 TI - Meeting the need for professional medical social workers in sight conservation. PMID- 20295388 TI - Is industry measuring up to modern standards of eye health and protection? PMID- 20295389 TI - Daylight in the schoolroom. PMID- 20295390 TI - The development of clinical pathology as a specialty of medicine; its position in the years ahead and thoughts on the future training of pathologists. PMID- 20295391 TI - Leukemia (summary of 100 cases) and lymphosarcoma complicated by pregnancy; cellular changes produced in guinea pigs by extracts of leukemic placenta. PMID- 20295392 TI - A noninfusion blood agar base for neisseriae, pneumococci and streptococci. PMID- 20295393 TI - Isolation of Shigella from the gallbladder of carrier. PMID- 20295394 TI - Nematode infestation in Pangasinan, Luzon, Philippine Islands. PMID- 20295395 TI - Use of Rh-negative mother's blood in transfusions in newborn babies. PMID- 20295396 TI - Granular cell myoblastoma (myoblastic myoma, rhabdomyome granulo-cellulaire). PMID- 20295397 TI - Acute liver necrosis in fulminating infectious hepatitis. PMID- 20295398 TI - Air embolism occurring during mastectomy; report of a fatal case. PMID- 20295399 TI - Fatal cerebral coccidioidomycosis; report of case. PMID- 20295400 TI - Infection with Isospora hominis; report of case. PMID- 20295401 TI - The clinical pathologist and the diagnosis of tuberculosis. PMID- 20295402 TI - Five types of so-called bronchial adenoma; a histopathologic study. PMID- 20295403 TI - Primary fibrosarcoma of the heart with a vertebral metastasis. PMID- 20295404 TI - Histologic changes occurring in the hemopoietic organs of albino rats after single injections of 2-chloroethyl vesicants; a quantitative study. PMID- 20295405 TI - Acute and chronic toxicity of methyl chloride; histopathologic observations. PMID- 20295406 TI - Histologic comparison of the brains of vitamin A-deficient and vitamin E deficient chicks. PMID- 20295407 TI - Adamantinoma in the tibia. PMID- 20295408 TI - Paracolon bacillus endocarditis of the pulmonic valve secondary to infected polycystic kidneys. PMID- 20295409 TI - Hodgkin's sarcoma of uterus. PMID- 20295410 TI - A peroxidase reaction in paraffin sections. PMID- 20295411 TI - [Not Available]. PMID- 20295413 TI - [Not Available]. PMID- 20295412 TI - [Not Available]. PMID- 20295414 TI - [Not Available]. PMID- 20295415 TI - [Not Available]. PMID- 20295416 TI - [Not Available]. PMID- 20295418 TI - [Not Available]. PMID- 20295417 TI - [Not Available]. PMID- 20295419 TI - [Not Available]. PMID- 20295420 TI - [Not Available]. PMID- 20295421 TI - [Not Available]. PMID- 20295422 TI - [Not Available]. PMID- 20295423 TI - [Not Available]. PMID- 20295424 TI - [Not Available]. PMID- 20295425 TI - [Not Available]. PMID- 20295426 TI - [Not Available]. PMID- 20295427 TI - [Not Available]. PMID- 20295428 TI - [Not Available]. PMID- 20295429 TI - [Not Available]. PMID- 20295430 TI - [Not Available]. PMID- 20295431 TI - [Not Available]. PMID- 20295432 TI - [Not Available]. PMID- 20295433 TI - [Not Available]. PMID- 20295434 TI - [Not Available]. PMID- 20295435 TI - [Not Available]. PMID- 20295436 TI - [Not Available]. PMID- 20295437 TI - [Not Available]. PMID- 20295438 TI - [Not Available]. PMID- 20295439 TI - [Not Available]. PMID- 20295440 TI - [Not Available]. PMID- 20295441 TI - [Not Available]. PMID- 20295442 TI - [Not Available]. PMID- 20295443 TI - [Not Available]. PMID- 20295444 TI - [Not Available]. PMID- 20295445 TI - [Not Available]. PMID- 20295446 TI - [Not Available]. PMID- 20295447 TI - [Not Available]. PMID- 20295448 TI - [Not Available]. PMID- 20295449 TI - [Not Available]. PMID- 20295450 TI - [Not Available]. PMID- 20295451 TI - [Not Available]. PMID- 20295452 TI - [Not Available]. PMID- 20295453 TI - [Not Available]. PMID- 20295454 TI - [Not Available]. PMID- 20295455 TI - [Not Available]. PMID- 20295456 TI - [Not Available]. PMID- 20295457 TI - [Not Available]. PMID- 20295458 TI - [Not Available]. PMID- 20295459 TI - [Not Available]. PMID- 20295460 TI - [Not Available]. PMID- 20295461 TI - [Not Available]. PMID- 20295462 TI - [Not Available]. PMID- 20295463 TI - [Not Available]. PMID- 20295464 TI - [Not Available]. PMID- 20295465 TI - [Not Available]. PMID- 20295466 TI - Art and the crippled child. PMID- 20295467 TI - A future for the cerebral palsied. PMID- 20295468 TI - Summer speech training. PMID- 20295469 TI - Help the cerebral palsied grow up. PMID- 20295470 TI - Animal research protects your health. PMID- 20295471 TI - Health service in the Pittsburgh schools. PMID- 20295472 TI - Ringworm of the scalp in Buffalo and vicinity. PMID- 20295473 TI - Sex education in the secondary schools. PMID- 20295474 TI - The child guidance clinic and other community resources. PMID- 20295475 TI - Effect of 6-methyl-2-thiouracil on rat foetuses and infantile rats. PMID- 20295476 TI - Toxicology of synthetic polysaccharide polysulphuric acid esters. PMID- 20295477 TI - A contribution to the pharmacodynamics of malonic, succinic, citric, aconitic, alpha-ketoglutaric and glutamic acid. PMID- 20295478 TI - Studies on the pharmacodynamics of cotoin. PMID- 20295479 TI - Effect of liver extract on lead anemia in rabbits. PMID- 20295480 TI - Some investigations on antithrombic substances. PMID- 20295481 TI - On the anticoagulant action of synthetic polysaccharide polysulphuric acids. PMID- 20295482 TI - On the chemotherapeutic properties of some thiazolylphenylsulphones. PMID- 20295483 TI - On the stimulant and depressant effects of pentamethylenetetrazol in sodium diethyl barbiturate depression. PMID- 20295484 TI - Action of quinine methochloride (methoquin) on neuromuscular transmission and its respiratory and cardiovascular actions. PMID- 20295485 TI - By-products of atomic energy for use by the pharmaceutical profession. PMID- 20295486 TI - Waksman and streptomycin. PMID- 20295487 TI - E. Merck of Darmstadt, Germany. PMID- 20295488 TI - A statistical approach to the determination of the weight tolerances of dry filled ampuls. PMID- 20295490 TI - ASSAY method for ergot and ergot preparations. PMID- 20295489 TI - Proposed N. F. specifications for methylcellulose. PMID- 20295491 TI - The problem of foreign botanicals. PMID- 20295492 TI - The occurrence of mature fruits of Piper cubeba in recently imported cubeb. PMID- 20295493 TI - Notes on the lead content of solution of lead subacetate, N. F. PMID- 20295494 TI - Progress in fungous disease therapy. PMID- 20295495 TI - Rutin, a new drug to fight hemorrhage. PMID- 20295496 TI - Should schools of pharmacy limit enrollment? PMID- 20295497 TI - Rapid control tests during manufacturing operations. PMID- 20295498 TI - The organic chemist. PMID- 20295499 TI - The biochemist. PMID- 20295500 TI - The bacteriologist. PMID- 20295501 TI - The pharmacologist. PMID- 20295502 TI - Clinical evaluation. PMID- 20295503 TI - The chemical engineer. PMID- 20295504 TI - Product development. PMID- 20295505 TI - Quality control. PMID- 20295506 TI - Food and Drug Administration. PMID- 20295507 TI - U.S. Public Health Service. PMID- 20295508 TI - The practicing pharmacist. PMID- 20295509 TI - The pharmacology of vasodepressor compounds structurally related to the sympathomimetic amines. PMID- 20295510 TI - The effect of perfusion through the isolated liver on the prothrombin activity of blood from normal and dicumarol treated rats. PMID- 20295511 TI - Cardiovascular effects of sodium caprylate in the cat. PMID- 20295512 TI - On the mechanism of paralysis resulting from toxin of Clostridium botulinum; the action of the toxin on acetylcholine synthesis and on striated muscle. PMID- 20295513 TI - Studies on veratrum alkaloids; receptor areas in the coronary arteries and elsewhere as revealed by the use of veratridine. PMID- 20295514 TI - The effect of BAL and BAL-glucoside therapy on the excretion and tissue distribution of injected cadmium. PMID- 20295515 TI - Central and autonomic effects following the combined administration of sodium arsenite and 2,3-dimercaptopropanol (BAL). PMID- 20295516 TI - Comparative central depressant actions of some 5-phenyl-5-alkyl barbituric acids. PMID- 20295517 TI - 3',5'-Dibromosulfanilanilide; toxicity, absorption, and metabolism. PMID- 20295518 TI - The effect of thorotrast on anaphylactic shock in the dog. PMID- 20295519 TI - The pharmacologic activity of N-methyl-beta-cyclohexyl-isopropylamine hydrochloride. PMID- 20295520 TI - Unmasking leprosy. PMID- 20295522 TI - This modern store has a history. PMID- 20295521 TI - Oriental pharmacy, U.S.A. PMID- 20295523 TI - The face, a mirror of character? PMID- 20295524 TI - Evaluating dishwashing detergents. PMID- 20295525 TI - CRYSTALLINE penicillin G. PMID- 20295526 TI - ELECTRON microscopy. PMID- 20295528 TI - DESOXYEPHEDRINE. PMID- 20295527 TI - CLINICAL use of luteotrophin. PMID- 20295529 TI - [Not Available]. PMID- 20295530 TI - [Not Available]. PMID- 20295531 TI - [Not Available]. PMID- 20295532 TI - [Not Available]. PMID- 20295533 TI - [Not Available]. PMID- 20295534 TI - [Not Available]. PMID- 20295535 TI - [Not Available]. PMID- 20295536 TI - [Not Available]. PMID- 20295537 TI - [Not Available]. PMID- 20295538 TI - [Not Available]. PMID- 20295539 TI - At the gates of heaven. PMID- 20295540 TI - The price of individuality; speculations about German national characteristics. PMID- 20295541 TI - On gambling. PMID- 20295542 TI - Dostoyevsky's Peasant Marey. PMID- 20295543 TI - Trends in affectlessness. PMID- 20295544 TI - The dynamism of anti-Semitism in Gentile and Jew. PMID- 20295545 TI - Studies in adjustment to visible injuries; evaluation of help by the injured. PMID- 20295546 TI - The psychological appraisal of children with neurological defects. PMID- 20295547 TI - Losses and gains in cognitive functions as related to electro-convulsive shocks. PMID- 20295548 TI - Simulated patterns on the Minnesota multiphasic personality inventory. PMID- 20295550 TI - Nondirective treatment of a conditioned motor block. PMID- 20295549 TI - The use of relaxation in short-term psychotherapy. PMID- 20295551 TI - Note on the scoring of the memory-for-designs test. PMID- 20295552 TI - Negro-white differences in intelligence in World War II; a note of caution. PMID- 20295553 TI - Antisocial compulsions induced under hypnotic trance. PMID- 20295554 TI - Rorschach variables in relation to ESP scores. PMID- 20295555 TI - The psychokinetic effect; further A.S.P.R. experiments. PMID- 20295556 TI - An exemplification of various neuroses and comparable Humm-Wadsworth temperament scale profiles with typical case briefs. PMID- 20295557 TI - Probing Canadian prejudices; a preliminary objective survey. PMID- 20295558 TI - Aurelius Augustine on imagination. PMID- 20295559 TI - [Not Available]. PMID- 20295560 TI - Verbal facility, sensitive affect, psychometrics; two palimpsest personalities. PMID- 20295561 TI - Suggestion and visual impression. PMID- 20295562 TI - The mentality of hydrocephalics and a description of an interesting case. PMID- 20295563 TI - The efficiency of the group Rorschach test in the psychiatric screening of Marine Corps recruits. PMID- 20295564 TI - Psychological factors in susceptibility to motion sickness. PMID- 20295565 TI - Body sway and non-visual factors. PMID- 20295566 TI - The relation between the percentage of most listeners to a radio station and the percentage of the total listening time obtained by it. PMID- 20295567 TI - The new public psychiatry. PMID- 20295568 TI - Mental hospitals, 1946. PMID- 20295569 TI - Mental hygiene in the disabling diseases. PMID- 20295570 TI - Some essentials in national mental-health planning. PMID- 20295571 TI - Factors in the development of state mental-health programs. PMID- 20295572 TI - Separation anxiety. PMID- 20295573 TI - Therapy; a feeling and doing process. PMID- 20295574 TI - The question-box method of group psychotherapy. PMID- 20295575 TI - Pattern for rehabilitation; the role of the educator. PMID- 20295576 TI - What hospitalization means to the mental patient, the community, and the hospital social worker. PMID- 20295577 TI - The mental patient in the community from the viewpoint of the family agency. PMID- 20295578 TI - The psychiatric social worker in a mental hospital. PMID- 20295579 TI - Some comments on Virginia's mental health program. PMID- 20295580 TI - The history of disease among the natives of Alaska. PMID- 20295582 TI - Legal aspects of planning for local health units. PMID- 20295581 TI - Local health district development in New York State. PMID- 20295583 TI - Legal aspects from the viewpoint of a state health department. PMID- 20295584 TI - Scope and facilities for local health units. PMID- 20295585 TI - Indispensable functions from viewpoint of the state health commissioner. PMID- 20295586 TI - Personnel and training for local health units. PMID- 20295587 TI - The state health commissioner looks at personnel and training. PMID- 20295589 TI - How to finance local health units. PMID- 20295588 TI - Principles of local government organization and finance. PMID- 20295590 TI - Relative financial needs of state and local health departments. PMID- 20295591 TI - Public relations as affecting financial needs for local health units. PMID- 20295593 TI - Physician participation in supporting local health units. PMID- 20295592 TI - Promoting public support for local health units. PMID- 20295594 TI - How to influence people. PMID- 20295595 TI - Promotional activities for local health units. PMID- 20295597 TI - Is leprosy a menace? PMID- 20295596 TI - Goitre; non-toxic and toxic. PMID- 20295598 TI - Schools for foodhandlers in Kentucky, 1945-46. PMID- 20295599 TI - Geriatrics. PMID- 20295600 TI - Social and economic background of present agitation for a medical care program. PMID- 20295601 TI - Some problems in the training of personnel. PMID- 20295602 TI - Crippled children in Connecticut; an analysis of the state register; geographic distribution. PMID- 20295603 TI - Eating place inspection. PMID- 20295604 TI - Cancer control. PMID- 20295605 TI - Modern anaesthetics. PMID- 20295606 TI - Public health in the second city. PMID- 20295607 TI - Pacific medical school. PMID- 20295608 TI - Nature cure in modern medicine. PMID- 20295609 TI - Chest surgery is new. PMID- 20295610 TI - Saharan surgeon. PMID- 20295611 TI - The doctor in industry. PMID- 20295612 TI - Britain faces her tuberculosis problem. PMID- 20295613 TI - Mental hospital. PMID- 20295614 TI - Study of selectees rejected from Armed Forces for pulmonary tuberculosis. PMID- 20295615 TI - Hudson County and infant health. PMID- 20295616 TI - The statistical program of the Census Bureau. PMID- 20295617 TI - Problems of multiple-punching with Hollerith machines. PMID- 20295618 TI - A critique of a method of making actuarial estimates for a compulsory health insurance system. PMID- 20295619 TI - Some observations on life reassurance. PMID- 20295622 TI - Further remarks on the relationship between the values of life annuities at different rates of interest, including a description of a method of first difference interpolation and a reference to annuities-certain. PMID- 20295620 TI - Two-variable developments of the n-ages method. PMID- 20295621 TI - The financial investigation of charitable funds. PMID- 20295623 TI - Percentage table for the estimation of sickness rates for special periods of sickness. PMID- 20295624 TI - Some notes on interpolation. PMID- 20295625 TI - CONTINUOUS mortality investigation; assured lives, 1939-43. PMID- 20295626 TI - The recent trend of mortality in England and Wales. PMID- 20295627 TI - Medical aspects of life in a prisoner of war camp. PMID- 20295628 TI - The history of state medicine in England; the Medical Department of the Privy Council. PMID- 20295629 TI - Penicillin for scarlet fever. PMID- 20295630 TI - The incidence of serum allergy in 1,000 cases of scarlet fever treated with anti scarlatinal serum. PMID- 20295631 TI - The evolution of official tuberculosis control in the United States. PMID- 20295632 TI - Digested sludge; an aid to the activated sludge process. PMID- 20295633 TI - Modernization of the B. O. D. test for determining the efficacy of sewage treatment processes. PMID- 20295634 TI - Preaerated raw sludge recirculation increases primary sedimentation efficiency at Denver. PMID- 20295635 TI - Control of sewer usage at Detroit, Michigan. PMID- 20295636 TI - The transmission of disease by sewage. PMID- 20295637 TI - Effects of ground garbage on sewage treatment processes. PMID- 20295638 TI - Sewage treatment at an African native community. PMID- 20295639 TI - A study of wastes from the synthetic rubber industry. PMID- 20295640 TI - British developments in sewage purification practice. PMID- 20295641 TI - Important considerations in sludge digestion; practical aspects. PMID- 20295642 TI - Important considerations in sludge digestion; microbiology and theory of anaerobic digestion. PMID- 20295643 TI - The digestion of sewage sludge containing various concentrations of solids. PMID- 20295644 TI - Phosphates in sewage and sludge treatment; quantities of phosphates. PMID- 20295645 TI - Operating and experimental observations on digestion of garbage with sewage solids. PMID- 20295646 TI - Modern practices in municipal water softening. PMID- 20295647 TI - A plea for sound economy in stream pollution abatement. PMID- 20295648 TI - On the mechanism of shock or general reaction of cells and organisms to injury. PMID- 20295649 TI - The technique of chest fluoroscopy. PMID- 20295651 TI - [Not Available]. PMID- 20295650 TI - Transposition of viscera, bronchiectasis and nasal polyps; a genetical analysis and a contribution to the problem of constitution. PMID- 20295652 TI - Roentgen diagnosis of phlegmonous gastritis. PMID- 20295653 TI - A system of formulae and curves bearing on the distribution of energy in the continuous roentgen spectrum. PMID- 20295654 TI - Primary carcinoma of the fallopian tube. PMID- 20295656 TI - [Not Available]. PMID- 20295655 TI - Complications of myelography by abrodil. PMID- 20295657 TI - Mediastinal tumors in leukosis. PMID- 20295658 TI - On the radiological examination of the eustachian tube in cases of chronic otitis. PMID- 20295659 TI - Electrokymograph for recording heart motion, improved type. PMID- 20295660 TI - Roentgen manifestations in the skull of metastatic carotid body tumor (paraganglioma) of meningeoma and of mucocele; a report of three unusual cases. PMID- 20295661 TI - Primary bronchogenic cancer mistakenly diagnosed as pulmonary tuberculosis; case reports with body section roentgenography. PMID- 20295662 TI - The vallecular sign; its diagnosis and clinical significance. PMID- 20295663 TI - Congenital aplasia of the lung; a case report. PMID- 20295664 TI - The diagnosis of Ascaris infestation by serial roentgen examination of the small intestine. PMID- 20295665 TI - Examination of the urinary and lower intestinal tracts before treatment of carcinoma of the cervix uteri. PMID- 20295666 TI - Congenital malformations induced in rats by roentgen rays; skeletal changes in the offspring following a single irradiation of the mother. PMID- 20295668 TI - Prominent inner malleolus; a cause of painful and enlarged ankle region. PMID- 20295667 TI - The correlation of tissue dose and clinical response in irradiation of bone tumors and of normal bone. PMID- 20295669 TI - Appearance and growth of ossification centers and increases in the body dimensions of white and Negro infants. PMID- 20295670 TI - A simple method for roentgenography of the chest presenting marked variations in density. PMID- 20295671 TI - Reasons for the common anatomic location of pulmonary tuberculosis. PMID- 20295672 TI - The roentgen findings in early coccidioidomycosis. PMID- 20295673 TI - Pulmonary sarcoidosis; the early roentgen findings. PMID- 20295674 TI - Roentgen therapy in Hodgkin's disease. PMID- 20295675 TI - The early effects of X-rays on the ovaries of the rat. PMID- 20295676 TI - A roentgenkymographic study of the heart in myasthenia gravis. PMID- 20295677 TI - Roentgen findings in torulosis; report of four cases. PMID- 20295678 TI - A study of 24,615 separation chest roentgenograms. PMID- 20295679 TI - Aortic aneurysm secondary to coarctation; report of a case showing calcification. PMID- 20295680 TI - Problems of acquired radioresistance of cancer; adaptation of tumor cells. PMID- 20295681 TI - X-ray technique. PMID- 20295682 TI - The anode heel effect in radiography. PMID- 20295683 TI - Roentgengrams of surgical and postmortem specimens. PMID- 20295684 TI - Modern X-ray physics in miniature. PMID- 20295685 TI - X-ray examination of the thymus of the newborn infant. PMID- 20295686 TI - [Not Available]. PMID- 20295687 TI - Case of spontaneous rupture of the subclavian artery. PMID- 20295688 TI - Cat bite; pasteurellosis; halisteresis. PMID- 20295689 TI - A study of new bone formation provoked by subperiosteal injections of blood plasma, extract of bone marrow, etc., an investigation by experiments on animals. PMID- 20295690 TI - Operative treatment of gallstone ileus without enterotomy. PMID- 20295691 TI - On diaphragmatic hernia. PMID- 20295692 TI - On shock during the healing stage of peritonitis. PMID- 20295693 TI - The problem of hypoproteinemia in delayed gastric emptying after stomach resection. PMID- 20295694 TI - Three cases of osteomyelitis in children treated with penicillin. PMID- 20295695 TI - Low spinal cord injuries following spinal anesthesia. PMID- 20295696 TI - A lenient method for reposition of fractures and dislocations of the vertebral column. PMID- 20295697 TI - An easily adjustable distraction apparatus. PMID- 20295698 TI - A contribution to the operative treatment (resection) of cancer of the rectum. PMID- 20295699 TI - An investigation, by experiments on animals, of the role played by the epiphysial cartilage in longitudinal growth. PMID- 20295700 TI - On the frequency of complications, especially those of long duration, after spinal anaesthesia. PMID- 20295701 TI - A case of double bladder; remarks on my earlier work of the same title. PMID- 20295702 TI - Total resection of the carcinomatous stomach. PMID- 20295703 TI - Malignant nasopharyngeal tumours manifesting themselves as parotid tumours. PMID- 20295704 TI - Treatment of cancer of the colon. PMID- 20295705 TI - [Not Available]. PMID- 20295707 TI - Drainage in operations on the bile passages. PMID- 20295706 TI - On spontaneous complete discharge of stones from the gallbladder and common duct. PMID- 20295708 TI - A new method of treating capillary haemangiomas. PMID- 20295709 TI - Postoperative emptying difficulties in direct connection with gastric resection. PMID- 20295710 TI - Postoperative pulmonary atelectasis. PMID- 20295711 TI - Caudal trans-sacral anesthesia in rectal surgery; its routine use in more than 2,000 cases. PMID- 20295712 TI - Injuries to the semilunar cartilages of the knee joint. PMID- 20295713 TI - Maxillofacial injuries; reconstructive surgery of the dehiscent parotid duct and dehiscent peripheral facial nerve. PMID- 20295714 TI - Late repair of massive tissue defects by the split skin-lined flap graft. PMID- 20295715 TI - Surgical approach to the tibial nerve below the popliteal fossa. PMID- 20295716 TI - Continuous, vertical mattress suture; its application and usefulness. PMID- 20295717 TI - Experiences with pulsating hematoma. PMID- 20295718 TI - Method for repair of posterior tibial nerve. PMID- 20295719 TI - Simple technic of suturing in gastrointestinal anastomoses. PMID- 20295720 TI - Reduction of rectal prolapse. PMID- 20295721 TI - Glenard's disease (generalized visceroptosis) the importance of some of its complications. PMID- 20295723 TI - Ligation of inferior vena cava for septic thrombophlebitis. PMID- 20295722 TI - Management of multiple compound facial wounds caused by whirling airplane propellor. PMID- 20295724 TI - Monteggia fracture. PMID- 20295725 TI - Spontaneous salpingo-colic fistula complicating pyosalpinx. PMID- 20295726 TI - Ligation of the inferior vena cava. PMID- 20295727 TI - New type of fastener for joint separations and oblique fractures. PMID- 20295728 TI - Apparatus for refrigeration anesthesia. PMID- 20295729 TI - New ligation knife facilitating subcutaneous ligation of varicose veins. PMID- 20295730 TI - Apparatus for rapid construction of molded splints. PMID- 20295731 TI - Burned and traumatized hands. PMID- 20295732 TI - Management of colostomies in the Fifteenth Hospital Center, England. PMID- 20295733 TI - A modified technic for total gastrectomy. PMID- 20295734 TI - Ruptured intervertebral disk in the cervical region; a report of 20 cases. PMID- 20295736 TI - Tuberculosis of bones and joints. PMID- 20295735 TI - Streptomycin and parachlorophenol in surgical infections. PMID- 20295737 TI - Infections of the bones and joints. PMID- 20295738 TI - Chronic arthritis. PMID- 20295739 TI - Penicillin in the treatment of infections in the nasal passages and sinuses. PMID- 20295740 TI - The nature of the pilonidal sinus. PMID- 20295741 TI - Drainage in infected cavernous sinus thrombosis. PMID- 20295743 TI - Intrathoracic neurogenic neoplasms, with a report of four cases. PMID- 20295742 TI - A preliminary note on a study of post-operative thrombosis, with special reference to a pre-thrombotic state. PMID- 20295744 TI - Bronchoscopy in post-operative pulmonary complications. PMID- 20295745 TI - Cystectomy. PMID- 20295746 TI - A case of prolapsed intervertebral disk, with ante-mortem and post-mortem findings. PMID- 20295747 TI - Peripheral traumatic aneurysm. PMID- 20295748 TI - Treatment of Trichomonas vaginalis vaginitis. PMID- 20295749 TI - Extensive hemangioma; report of cases. PMID- 20295750 TI - The choice of operation for the treatment of arteriovenous fistulas. PMID- 20295751 TI - The action of urea and some of its derivatives on bacteria; the effect of a mixture of urethane and sulfanilamide on the bacterial flora of infected wounds in man. PMID- 20295752 TI - Gelatin solution in the treatment of shock from graded hemorrhage. PMID- 20295754 TI - A comparison of suture and nonsuture methods for the anastomosis of veins. PMID- 20295753 TI - Circumscribed chronic suppurative mastitis simulating cancer. PMID- 20295756 TI - Malignant lymphoma; the value of radical surgery in selected cases. PMID- 20295755 TI - Origin and development of the erect posture. PMID- 20295757 TI - Digestion of living tissue by the hyperacid stomach; an experimental study. PMID- 20295758 TI - Adolescent primigravida. PMID- 20295759 TI - Results of treatment of epidermoid carcinoma of the anus and rectum. PMID- 20295760 TI - Management of jaw fractures. PMID- 20295761 TI - Surgery of the posterior interosseous branch of the radial nerve; analysis of 58 cases. PMID- 20295762 TI - Histopathology of the gastric semisquamous epithelial layer. PMID- 20295763 TI - Notes on the history of resuscitation in the Mediterranean Theater of Operations. PMID- 20295764 TI - The value of red cell transfusions. PMID- 20295765 TI - Anemia in burns. PMID- 20295766 TI - Did cholera defeat Custer? PMID- 20295767 TI - The treatment of injuries of the spinal cord. PMID- 20295768 TI - Chemosurgical treatment of cancer of the ear; a microscopically controlled method of excision. PMID- 20295769 TI - Successful suture of the abdominal aorta for arteriovenous fistula. PMID- 20295770 TI - Evaluation of the basal vascular tone test as an indication for sympathectomy in the treatment of surgical lesions of the major arteries. PMID- 20295771 TI - The fluorescein wheat test for collateral circulation in the preoperative evaluation of patients with aneurysms and arteriovenous fistulas. PMID- 20295772 TI - Direct measurement of blood pressure within arterial aneurysms and arteriovenous fistulas. PMID- 20295773 TI - A method of rapid transfusion into the femoral vessels in patients without adequate peripheral superficial veins. PMID- 20295774 TI - Wound healing studies on several substances recommended for the treatment of burns. PMID- 20295775 TI - The treatment of bedsores in paraplegic patients. PMID- 20295776 TI - Acute cholecystitis, with special reference to the occurrence of jaundice. PMID- 20295777 TI - Intrathecal penicillin in bacterial meningitis. PMID- 20295778 TI - Intra-arterial penicillin in the surgical treatment of infections of the extremities. PMID- 20295779 TI - The importance of precise bacteriologic data in the treatment of infections of the urogenital tract. PMID- 20295780 TI - The postgastrectomy syndrome. PMID- 20295781 TI - Three hundred seventy-four acute war wounds of the thorax. PMID- 20295782 TI - The six subphrenic spaces; applied anatomy and surgical considerations. PMID- 20295783 TI - Cotton versus catgut as suture material in herniorrhaphy. PMID- 20295784 TI - Dislocation at the acromioclavicular articulation; a note on technique of radiographic examination of the shoulder in suspected dislocation at the acromioclavicular or humeroscapular articulation. PMID- 20295785 TI - Tracheotomy in maxillofacial surgery. PMID- 20295786 TI - Pleuralization of the left-bronchus in pneumonectomy. PMID- 20295787 TI - The evaluation of disability and treatment in hemiplegia. PMID- 20295788 TI - A survey method for radiation coverage patterns of infra-red generators. PMID- 20295789 TI - Vertebral changes following experimentally produced muscle imbalance; preliminary report. PMID- 20295790 TI - A poliomyelitis program in a general hospital. PMID- 20295791 TI - Muscle strength and the weather. PMID- 20295792 TI - Trends in training in physical medicine. PMID- 20295793 TI - Disability resulting from injuries to peripheral nerves. PMID- 20295794 TI - Kinesotherapy and extension treatment in rheumatoid arthritis. PMID- 20295795 TI - Bismuth therapy and physiotherapy in rheumatoid arthritis. PMID- 20295796 TI - Physical medicine in Switzerland; its development and present position. PMID- 20295797 TI - The early treatment of injuries. PMID- 20295798 TI - Injuries seen in a factory ambulance room. PMID- 20295799 TI - Venereal diseases in relationship to industrial medicine. PMID- 20295800 TI - Care of the chronic sick. PMID- 20295801 TI - The fundamental position of rest; its use in certain conditions of the spine, especially sciatica. PMID- 20295802 TI - Some medical problems of the asbestos cement industry. PMID- 20295804 TI - The way to natural childbirth. PMID- 20295803 TI - Electromyography. PMID- 20295805 TI - Relaxation. PMID- 20295806 TI - Medical philosophical treatise on mental alienation. PMID- 20295807 TI - The use of social and non-equipment games in occupational therapy. PMID- 20295808 TI - Kinetic analysis of crafts and occupations. PMID- 20295809 TI - Occupational therapy in psychiatric treatment. PMID- 20295810 TI - A new formula for teaching ambulation to paraplegics. PMID- 20295811 TI - Studies in psychiatric occupational therapy. PMID- 20295812 TI - Social service in the rehabilitation process. PMID- 20295813 TI - Physical therapy management of lower extremity amputees. PMID- 20295814 TI - Emphasis on exercise as a therapeutic agent; in a naval physical therapy department. PMID- 20295815 TI - The physical therapist overseas. PMID- 20295816 TI - Physical therapy in the industrial clinic. PMID- 20295817 TI - Physical therapy in a curative workshop. PMID- 20295818 TI - Post sanatorium care. PMID- 20295819 TI - [Not Available]. PMID- 20295820 TI - [Not Available]. PMID- 20295821 TI - [Not Available]. PMID- 20295822 TI - [Not Available]. PMID- 20295823 TI - [Not Available]. PMID- 20295824 TI - [Not Available]. PMID- 20295825 TI - [Not Available]. PMID- 20295827 TI - [Not Available]. PMID- 20295826 TI - [Not Available]. PMID- 20295828 TI - [Not Available]. PMID- 20295829 TI - [Not Available]. PMID- 20295830 TI - [Not Available]. PMID- 20295831 TI - [Not Available]. PMID- 20295832 TI - [Not Available]. PMID- 20295833 TI - [Not Available]. PMID- 20295834 TI - [Not Available]. PMID- 20295835 TI - [Not Available]. PMID- 20295836 TI - [Not Available]. PMID- 20295837 TI - [Not Available]. PMID- 20295838 TI - [Not Available]. PMID- 20295839 TI - [Not Available]. PMID- 20295840 TI - Problems of renal lithiasis. PMID- 20295841 TI - Abacterial pyuria from a new angle. PMID- 20295842 TI - Retrocaval ureter with description of an operation case complicated by ureteric calculus. PMID- 20295843 TI - A pyelographic test for renal fixity during respiration. PMID- 20295844 TI - Reiter's disease followed by true infective abacterial pyuria. PMID- 20295845 TI - Urinary fistula following vasostomy. PMID- 20295846 TI - An unusual case of multiple and widespread calculi. PMID- 20295847 TI - The testis biopsy in infertility. PMID- 20295848 TI - An unusually large pelvic hydronephrosis treated by excision of the kidney cap. PMID- 20295849 TI - Fibrin foam and gelfoam in experimental kidney wounds. PMID- 20295850 TI - Gelfoam hemostasis in prostatic surgery. PMID- 20295851 TI - The use of absorbable gauze (oxidized cellulose) in urological surgery. PMID- 20295852 TI - The use of gelfoam in transurethral resection. PMID- 20295853 TI - Agenesis of the right kidney with a retroperitoneal cyst arising in a persistent metanephros. PMID- 20295854 TI - Effects of overdistention of the renal pelvis and ureter; a study on pyelovenous backflow. PMID- 20295855 TI - Aneurysm of the hypogastric artery producing urinary tract obstruction; report of a case. PMID- 20295856 TI - Reimplantation of the ureter into the bladder by a flap method. PMID- 20295857 TI - Vaginal cystectomy. PMID- 20295858 TI - Pseudosphincter formation in neurogenic bladder. PMID- 20295859 TI - Foreign body (Kirschner wire) removed from bladder. PMID- 20295860 TI - Enormous mucoid cyst of the urachus. PMID- 20295861 TI - A new resectoscope knife. PMID- 20295862 TI - Hemorrhagic infarction of the testicle in the newborn. PMID- 20295863 TI - Benign solid tumor of the epididymis. PMID- 20295864 TI - Angioma of the glans penis. PMID- 20295865 TI - Suture meatotomy. PMID- 20295866 TI - Excision of the internal spermatic vein for varicocele. PMID- 20295867 TI - Treatment of chronic nonspecific prostatitis with oral penicillin. PMID- 20295868 TI - Synergistic action between the sulfonamides, certain dyes, and streptomycin against gram-negative bacteria; preliminary report. PMID- 20295869 TI - Streptomycin in genito-urinary infections. PMID- 20295870 TI - Experiences and lessons of emergency urological surgery in war. PMID- 20295871 TI - A method of sterilizing catheters and storing them for immediate use. PMID- 20295872 TI - Postwar progress against prostitution; unfinished business. PMID- 20295873 TI - IS commercialized prostitution returning? a seven year survey; an analysis of 2,626 studies made by the American Social Hygiene Association, January 1, 1940 to December 31, 1946, in 1,177 communities. PMID- 20295875 TI - MILESTONES in the march against prostitution. PMID- 20295874 TI - Are we holding our own against prostitution? a postwar review of progress in the United States. PMID- 20295876 TI - The cost of venereal disease contact investigation in Tennessee. PMID- 20295877 TI - North Carolina's experience with the investigation of suspected venereal disease contacts. PMID- 20295878 TI - Significance and interpretation of quantitative blood tests for syphilis. PMID- 20295879 TI - The blood in equine periodic ophthalmia. PMID- 20295880 TI - Immunologic and clinical studies on plasma fractions from domestic livestock; the antibody content of porcine and bovine gamma globulin. PMID- 20295881 TI - Concentrations of penicillin in the bovine mammary gland following infusion and the penicillin tolerance of certain streptococci. PMID- 20295882 TI - Permanent enteric fistulas for studies of ruminant digestion, assimilation, and elimination. PMID- 20295883 TI - Milk fever (parturient paresis) as a manifestation of alkalosis. PMID- 20295884 TI - The resistance of chronic staphylococcic bovine mastitis to massive penicillin therapy. PMID- 20295885 TI - Vibrionic abortion in cattle. PMID- 20295886 TI - Antigenic relationship between the genus Mycobacterium and the genus Corynebacterium in goats and cattle. PMID- 20295887 TI - Experimental treatment of trichostrongylosis in sheep with phenothiazine. PMID- 20295888 TI - Streptomycin in the treatment of experimental brucellosis of guinea pigs. PMID- 20295889 TI - The chemotherapy of cecal coccidiosis. PMID- 20295890 TI - Studies in pullorum disease; antigenic differences in strains of Salmonella pullorum. PMID- 20295891 TI - Cultivation of the virus of infectious bronchitis of chickens in embryonated chicken eggs. PMID- 20295892 TI - Escherichia coli in the blood stream of adult fowl affected with the ocular form of fowl paralysis. PMID- 20295893 TI - The toxicity of sulfamerazine to chickens. PMID- 20295894 TI - Studies on fly strike in Merino sheep; the effect of tail-length on susceptibility to fly strike in ewes. PMID- 20295895 TI - PROGRESS report on the investigations into the etiology and control of enzootic (toxaemic) jaundice of sheep. PMID- 20295896 TI - The practice of veterinary medicine in a veterinary service district in Saskatchewan. PMID- 20295897 TI - An outbreak of mastitis caused by Streptococcus pyogenes and the effect of treatment with penicillin. PMID- 20295898 TI - Studies in pullorum disease; disinfection of incubators with propylene and triethylene glycol. PMID- 20295899 TI - Comparison of human and bovine type tuberculin on guinea pigs sensitized with several acid-fast microorganisms. PMID- 20295900 TI - Non-specific pullorum agglutination reactions; post mortem studies on fowl exhibiting non-specific reactions over an extended period. PMID- 20295902 TI - [Not Available]. PMID- 20295903 TI - Osteoporosis in horses. PMID- 20295904 TI - The role of nutrition in livestock improvement. PMID- 20295905 TI - Carcinoma of the horn in bovines. PMID- 20295906 TI - Indigenous drugs of India, their veterinary and economic aspects. PMID- 20295907 TI - Occurrence of Bact. alcaligenes sp. in duck eggs. PMID- 20295909 TI - Avian spirochetosis. PMID- 20295908 TI - Pervious urachus in a heifer-calf. PMID- 20295910 TI - Caesarean section in a Pomeranian. PMID- 20295911 TI - A case of mixed protozoal infection in a dog. PMID- 20295912 TI - So, you are a member of the American Veterinary Medical Association. PMID- 20295913 TI - MEXICAN outbreak of foot-and-mouth disease. PMID- 20295914 TI - Cesarean section and torsion of the uterus in cows. PMID- 20295915 TI - Endocrine therapy in veterinary medicine. PMID- 20295916 TI - Clinical use of sulfamerazine in the treatment of hemorrhagic septicemia and pneumonia in cattle. PMID- 20295917 TI - Penicillin in canine distempter meningitis. PMID- 20295918 TI - Panel discussion on poultry problems. PMID- 20295919 TI - Generalized tuberculosis in a goat. PMID- 20295920 TI - Suspected arthritic brucellosis in a gilt. PMID- 20295921 TI - Formulating dog foods of high quality. PMID- 20295922 TI - RHODE ISLAND Supreme Court upholds recognition of approved schools. PMID- 20295923 TI - The amounts of feeds and nutrients in the rumen of cattle throughout a 24-hour period as affected by plane of feeding and character of ration. PMID- 20295924 TI - Thiamine content of raw and cooked pork tissues from pigs of known dietary history. PMID- 20295925 TI - The effect of intake of garbage fat upon fat content of sow's milk. PMID- 20295926 TI - The influence of thiouracil and thiourea on the growth and fattening of lambs. PMID- 20295927 TI - The effect of thiouracil in the ration of growing swine. PMID- 20295928 TI - The effect of thiouracil on the growth and fattening of yearling steers. PMID- 20295929 TI - Heat tolerance comparisons between Jersey and Holstein cows. PMID- 20295930 TI - Effects of artificial showers, natural rain and wallowing on the body temperature of animals. PMID- 20295931 TI - Carotene blood levels and reproductive performance in range Hereford cattle. PMID- 20295932 TI - The relative accuracy of one-day and three-day weaning weights of calves. PMID- 20295933 TI - Effect of techniques of preparing semen smears for staining on the morphology of bull spermatozoa. PMID- 20295935 TI - Breed crosses used in the development of Targhee sheep. PMID- 20295934 TI - Refining methods for using opal blue stain in evaluating ram semen. PMID- 20295936 TI - No. 6 Indian Field Veterinary Hospital. PMID- 20295937 TI - Extracts from the diary of a veterinary officer in the M.E.F. and C.M.F. PMID- 20295938 TI - The transport of animals by sea between South Africa and India during World War II. PMID- 20295939 TI - The treatment of contaminated wounds. PMID- 20295940 TI - Castration of swine. PMID- 20295941 TI - Diagnosis and treatment of early traumatic gastritis of bovines. PMID- 20295942 TI - Field studies of sulfamerazine in the control of pullorum and some other diseases of domestic birds. PMID- 20295943 TI - The management of pseudo-cyesis and pyometra. PMID- 20295944 TI - Acanthosis nigricans possibly an A avitaminosis. PMID- 20295946 TI - Psittacosis. PMID- 20295945 TI - The tonsillar tissue of the dog. PMID- 20295947 TI - Reduction of fracture in a Shetland pony. PMID- 20295948 TI - An unusual case of insecticide poisoning in pigs. PMID- 20295949 TI - D. D. T. as an anti-blowfly dip. PMID- 20295950 TI - Ancient horse-shoes. PMID- 20295951 TI - Joint-ill in foals (pyosepticaemia) with special reference to the prophylactic treatment of the foal at birth. PMID- 20295952 TI - Chemotherapy of Erysipelothrix rhusiopathiae infections in mice with streptomycin. PMID- 20295953 TI - Prostatic disease in the dog; clinical manifestations and treatment. PMID- 20295954 TI - Common ailments of canaries. PMID- 20295955 TI - Lameness of undetermined cause in cattle associated with gangrene. PMID- 20295956 TI - SEQUEL TO INOCULATION against Corynebacterium pyogenes (summer) mastitis; full text of Mr. Justice Hallett's judgment in the Chester case. PMID- 20295957 TI - The functions of the university. PMID- 20295958 TI - The diagnosis of traumatic reticulitis and pericarditis of bovines. PMID- 20295960 TI - Moor sickness. PMID- 20295959 TI - Some practical aspects of Corynebacterium pyogenes infections in cattle. PMID- 20295961 TI - A case of mistaken diagnosis: lipoma diagnosed as dead foetus. PMID- 20295962 TI - Calfhood vaccination against Bang's disease, using an aerobic strain of Brucella abortus of moderate virulence. PMID- 20295963 TI - The recreations of veterinary surgeons. PMID- 20295964 TI - Salmonella enteritidis var. dublin infection in a cow resulting in an outbreak of human gastro-enteritis. PMID- 20295965 TI - INOCULATION risks; legal liability of veterinary surgeons providing and using defective materials. PMID- 20295966 TI - Bacterial chemotherapy in veterinary medicine. PMID- 20295967 TI - Unusual foreign body; dog. PMID- 20295968 TI - Some new and rare records of piroplasmosis with a list of the species of Babesia and Theileria so far recorded from Egypt. PMID- 20295969 TI - Greyhound racing. PMID- 20295970 TI - Demodectic mange in the bovine. PMID- 20295972 TI - The relation of husbandry to animal health. PMID- 20295971 TI - Diet and canine hysteria. PMID- 20295973 TI - Soluthiazole as curative agent for a husky cough of unascertained origin in pigs. PMID- 20295974 TI - Infectious feline agranulocytosis or malignant panleucopenia. PMID- 20295975 TI - A year in general practice. PMID- 20295976 TI - Treatment of fascioliasis of cattle and sheep with a suspension of hexachlorethane and bentonite. PMID- 20295977 TI - Diet and canine hysteria. PMID- 20295978 TI - CAREERS in zoology. PMID- 20295979 TI - Feline enteritis and feline distemper; a survey of the literature. PMID- 20295980 TI - International veterinary cooperation, a necessity. PMID- 20295981 TI - Rupture in a foal and its reduction. PMID- 20295982 TI - The relative insecticidal activities of DDT and related organic molecules. PMID- 20295984 TI - Notes on some Maine shrews. PMID- 20295983 TI - A study of the deer and elk herds of Rocky Mountain National Park, Colorado. PMID- 20295985 TI - Notes on the natural history of the bat Corynorhinus rafinesquii in California. PMID- 20295986 TI - Paternal care of young mice of the genus Peromyscus. PMID- 20295987 TI - A deer-coyote episode. PMID- 20295988 TI - Notes on Mexican mammals. PMID- 20295989 TI - Two new cotton rats. PMID- 20295990 TI - Spontaneous neoplasms in fishes; fibro-carcinoma-like growth in the stomach of Borophryne apogon Regan, a deep-sea ceratioid fish. PMID- 20295991 TI - Studies on the genus Hirudinella, giant trematodes of scombriform fishes. PMID- 20295993 TI - Lysis in vitro of sensitized leucocytes by ragweed antigen. PMID- 20295992 TI - Histamine antagonists; comparative antianaphylactic activity of some new antihistaminic drugs. PMID- 20295994 TI - Pollen tolerance; its bearing on the treatment of hay fever. PMID- 20295995 TI - Contact-type eczematous dermatitis; modern classifications and remarks on therapy. PMID- 20295996 TI - Occupational dermatitis; with special reference to eczema-dermatitis of the hands. PMID- 20295997 TI - Some problems of atopic dermatitis in infancy and childhood. PMID- 20295998 TI - Atopic dermatitis in infants, children, and adults; with special reference to the role of inhalants and dander. PMID- 20295999 TI - Antibodies to ragweed extract; demonstration by collodion particle technique in immune rabbit serum but not in serum of treated patients. PMID- 20296000 TI - Anaphylactogenic properties of heparin in the guinea pig. PMID- 20296001 TI - Blood studies in allergy; variations in eosinophiles following test feeding of foods. PMID- 20296002 TI - The sensitizing factor in merthiolate. PMID- 20296003 TI - Allergy (asthma) to ingested gum tragacanth; a case report. PMID- 20296004 TI - Structural proteins and oriented lipoids in the cytoplasm of secreting and resorbing epithelial cells. PMID- 20296005 TI - [Not Available]. PMID- 20296006 TI - [Not Available]. PMID- 20296007 TI - [Not Available]. PMID- 20296008 TI - [Not Available]. PMID- 20296009 TI - Effect of desoxicorticosterone acetate on kidneys of male white mice. PMID- 20296010 TI - The torsion of the humerus; its localization, cause and duration in man. PMID- 20296011 TI - A cytochemical survey of phosphatases in mammalian liver, pancreas and salivary glands. PMID- 20296012 TI - The placentation of the American shrews, Blarina brevicauda and Sorex fumeus. PMID- 20296013 TI - An experimental study of lymph node regeneration in rabbits. PMID- 20296014 TI - [Not Available]. PMID- 20296015 TI - [Not Available]. PMID- 20296016 TI - Facts and speculations concerning the origin of Homo sapiens. PMID- 20296017 TI - Witch-fear in post-contact Kaska society. PMID- 20296018 TI - Anthropology during the war; the Arab world. PMID- 20296019 TI - The rate of nitrogen elimination from the body through the lungs. PMID- 20296020 TI - An electronic warning device for oxygen breathing systems. PMID- 20296021 TI - Studies on positive pressure respiration; effect of continuous pressure breathing on arterial blood gases at high altitude. PMID- 20296022 TI - Arterial oxygen saturation at altitude. PMID- 20296023 TI - The influence of cold upon the efficiency of man. PMID- 20296024 TI - Occurrence of bends, scotomata and hemianopsia at altitudes below 20,000 feet. PMID- 20296025 TI - Evaluation of certain tests of physical fitness. PMID- 20296026 TI - The martinet. PMID- 20296027 TI - Air evacuation activities. PMID- 20296028 TI - The physical principles involved in pilot comfort and efficiency. PMID- 20296029 TI - Medical care of casualties in long distance air evacuation. PMID- 20296030 TI - The changes in pressure in the peritoneal cavity produced by sudden deceleration of experimental animals. PMID- 20296031 TI - Effect of sulfamethazine on the coccidian parasite, Eimeria tenella, of chickens. PMID- 20296032 TI - Developmental stages in the life cycle of Eimeria tenella affected by sulfamethazine treatment. PMID- 20296033 TI - The relative susceptibility of 41 sweetpotato varieties, introductions, and seedlings to the root-knot nematode, Heterodera marioni (Cornu) Goodey. PMID- 20296034 TI - Preliminary tests to determine the nematocidal and fungicidal properties of certain chemical compounds when used as soil fumigants. PMID- 20296035 TI - A note on the fungoid nature of certain internal structures of Miescher's sacs (Sarocystis) from a naturally infected sheep and a naturally infected duck. PMID- 20296036 TI - Growth rate of pigs fed skim milk to control intestinal parasites. PMID- 20296037 TI - A note on the caudal papillae of the male of Wehr dikmansia cervipedis (Wehr and Dikmans, 1935) Caballero, 1945. PMID- 20296038 TI - The anthelmintic action of toluenes in dogs. PMID- 20296039 TI - Diagnosis of gastrointestinal nematode parasitism of sheep by differential egg counts. PMID- 20296040 TI - Preliminary note on the successful breeding of an intermediate host of the Asiatic blood fluke. PMID- 20296041 TI - The problem-centered biology laboratory study. PMID- 20296042 TI - The profession of medical technology. PMID- 20296043 TI - APPROVED schools for clinical laboratory technicians. PMID- 20296044 TI - The control and treatment of parasites in cattle. PMID- 20296045 TI - The pallial organs in the aspidobranch Gastropoda and their evolution throughout the Mollusca. PMID- 20296046 TI - [Not Available]. PMID- 20296047 TI - [Not Available]. PMID- 20296048 TI - [Not Available]. PMID- 20296049 TI - [Not Available]. PMID- 20296050 TI - [Not Available]. PMID- 20296051 TI - [Not Available]. PMID- 20296052 TI - [Not Available]. PMID- 20296053 TI - Heart disease; some views and comments. PMID- 20296054 TI - [Not Available]. PMID- 20296055 TI - High oxygen concentration under normal and increased respiratory pressure in cardiac pain and in pulmonary edema. PMID- 20296056 TI - An unusual electrocardiographic pattern of the myocardial infarction type(QT1C5 6). PMID- 20296057 TI - 2-Thiouracil in heart failure and in angina pectoris. PMID- 20296058 TI - Heart disease and pregnancy. PMID- 20296059 TI - Studies on the biosynthesis of penicillin. PMID- 20296060 TI - The enzymatic inactivation of indoleacetic acid; some characteristics of the enzyme contained in pea seedlings. PMID- 20296061 TI - Assimilation of acetate by yeast. PMID- 20296062 TI - Studies on the sulfur metabolism of Escherichia coli; the growth characteristics and metabolism of a mutant strain requiring methionine. PMID- 20296063 TI - Studies on the sulfur metabolism of Escherichia coli; interrelations of norleucine and methionine in the nutrition of Escherichia coli and of a methionine-requiring mutant of Escherichia coli. PMID- 20296064 TI - Studies on the sulfur metabolism of Escherichia coli; mutant strains of Escherichia coli unable to utilize sulfate for their complete sulfur requirements. PMID- 20296065 TI - The production of exocellular pectic enzymes by Penicillium chrysogenum; on the formation and adaptive nature of polygalacturonase and pectinesterase. PMID- 20296066 TI - The oxidation of carbohydrates by a surface strain of Penicillium notatum. PMID- 20296067 TI - The apparent concentration of free tryptophan, histidine and cystine in normal human urine measured microbiologically. PMID- 20296068 TI - The apparent concentration of free tryptophan, histidine and cystine in pathological human urine measured microbiologically. PMID- 20296069 TI - The apoenzymatic nature of adaptation to galactose fermentation. PMID- 20296070 TI - The synthesis of S-carboxymethylhomocysteine and S-beta-carboxyethylhomocysteine and a study of their availability for growth of rats maintained on a low-casein diet. PMID- 20296071 TI - The enzymatic conversion of tryptophan to auxin by spinach leaves. PMID- 20296072 TI - Interaction between tobacco mosaic virus and bovine serum albumin. PMID- 20296073 TI - The management of antro-buccal fistula. PMID- 20296074 TI - The necessity of close co-operation between the medical and dental professions. PMID- 20296075 TI - Sialolithiasis; a case report. PMID- 20296076 TI - Epitheliomatous development in dental cyst. PMID- 20296077 TI - Normal and abnormal occlusion of the teeth of Australian aboriginal children. PMID- 20296078 TI - The use of acrylic resins in restorative dentistry. PMID- 20296079 TI - The relationship of general medicine to diseases of the mouth. PMID- 20296080 TI - General anaesthetics for dental surgery. PMID- 20296081 TI - Dental health education in N.S.W. PMID- 20296082 TI - Periodontal conditions; etiologic factors in management. PMID- 20296083 TI - Anterior fixed bridge prosthesis including acrylic resins. PMID- 20296084 TI - Submucous surgery for better denture service. PMID- 20296085 TI - ROLE of fluorine in dental caries; fluorination of drinking water. PMID- 20296087 TI - The future of dentistry. PMID- 20296086 TI - COUNCIL discusses present status of sulfathiazole gum. PMID- 20296088 TI - The role of ethyl chloride as an obtundent in cavity preparation. PMID- 20296089 TI - Reactions pulpaires aux ciments silicates. PMID- 20296090 TI - [Not Available]. PMID- 20296091 TI - Operation of the dental program of the Veterans Administration in Pennsylvania. PMID- 20296092 TI - The present status and treatment of periodontal diseases. PMID- 20296093 TI - Protective posture for dentists. PMID- 20296094 TI - Four pioneers in the science of nutrition, Lind, Rumford, Chadwick, and Graham. PMID- 20296095 TI - Experiments in changing food habits. PMID- 20296096 TI - Protein therapy in emaciation. PMID- 20296097 TI - The loss of ascorbic acid in the preparation of old and freshly harvested potatoes. PMID- 20296098 TI - The loss of ascorbic acid in potatoes during storage. PMID- 20296099 TI - Vitamin retention and palatability of evaporated apricots. PMID- 20296100 TI - Studies on riboflavin-deficiency with a simple method. PMID- 20296101 TI - [Not Available]. PMID- 20296102 TI - [Not Available]. PMID- 20296103 TI - [Not Available]. PMID- 20296104 TI - [Not Available]. PMID- 20296106 TI - [Not Available]. PMID- 20296105 TI - [Not Available]. PMID- 20296107 TI - [Not Available]. PMID- 20296108 TI - [Not Available]. PMID- 20296109 TI - [Not Available]. PMID- 20296110 TI - [Not Available]. PMID- 20296111 TI - [Not Available]. PMID- 20296112 TI - Hungerdiseases during the period of famine in 1945. PMID- 20296113 TI - [Not Available]. PMID- 20296114 TI - [Not Available]. PMID- 20296115 TI - The interpretation of estrogenic assays. PMID- 20296116 TI - The imposition of diurnal ovulatory and temperature rhythms by periodic feeding of hens maintained under continuous light. PMID- 20296117 TI - The effect of pregnancy complicated by alloxan diabetes on the fetuses of dogs, rabbits and rats. PMID- 20296118 TI - Effect of thyroidectomy on the conversion of carotene to vitamine A. PMID- 20296119 TI - Regulation of pituitary adrenocorticotrophic activity during the response of the rat to acute stress. PMID- 20296120 TI - The role of the adrenal cortex in mammary development and its relation to the mammogenic action of the anterior pituitary. PMID- 20296121 TI - Action in vitro of thyrotropic hormone and iodide on thyroid cells. PMID- 20296122 TI - Fluctuations in the estrogen level throughout the menstrual cycle of one woman. PMID- 20296123 TI - Lactogenic hormone and fat metabolism. PMID- 20296124 TI - Malpractice and breach of contract in medical practice. PMID- 20296125 TI - Diplopodia; a lethal form of polydactyly in chickens. PMID- 20296126 TI - Inducing polyploidy in peach varieties. PMID- 20296127 TI - More wishful thinking about Mongolian imbecility. PMID- 20296128 TI - Color on the legs of sheep; its inheritance in the Columbia and Targhee breeds. PMID- 20296130 TI - [Not Available]. PMID- 20296129 TI - The inheritance of streblomicrodactyly. PMID- 20296131 TI - A new method of preventing tubal occlusion following operations for sterility. PMID- 20296132 TI - [Not Available]. PMID- 20296133 TI - [Not Available]. PMID- 20296134 TI - [Not Available]. PMID- 20296135 TI - Intermenstrual pain. PMID- 20296136 TI - Inactivation of oestrogens by the human liver. PMID- 20296137 TI - [Not Available]. PMID- 20296138 TI - [Not Available]. PMID- 20296139 TI - [Not Available]. PMID- 20296140 TI - [Not Available]. PMID- 20296141 TI - [Not Available]. PMID- 20296142 TI - [Not Available]. PMID- 20296143 TI - Rupture of the membranes before the onset of labour. PMID- 20296144 TI - A case of ruptured uterus. PMID- 20296145 TI - The association of the Guillain-Barre syndrome with infectious mononucleosis; with a report of two fatal cases. PMID- 20296146 TI - Chronic neutropenia; report of a case not cured by splenectomy. PMID- 20296147 TI - Studies on the physiology of the white blood cell; the glycogen content of leukocytes in leukemia and polycythemia. PMID- 20296148 TI - Observations on the anemia in ducks infected with P. lophurae. PMID- 20296149 TI - Dietary factors concerned in erythropoiesis. PMID- 20296150 TI - The mammalian red corpuscle. PMID- 20296151 TI - Service organizations for the relief of the sick and wounded. PMID- 20296152 TI - Care of the sick and wounded in early wars; the prehistory of ambulance service. PMID- 20296153 TI - Baron Larrey, father of ambulance service. PMID- 20296154 TI - The development of ambulance service in the armies of Great Britain, the United States and other countries. PMID- 20296155 TI - Civilian ambulance service. PMID- 20296156 TI - From theatrum anatomicum to medical museum. PMID- 20296157 TI - The origin of hygiene and health museums. PMID- 20296159 TI - The potentized drug which is specific to the patient. PMID- 20296158 TI - Health and hygiene at international expositions. PMID- 20296160 TI - Homeopathic treatment of war neuroses. PMID- 20296161 TI - Homeopathy, the medical stabilizer. PMID- 20296162 TI - Homeopathic education. PMID- 20296163 TI - Homeopathic education. PMID- 20296165 TI - Angina pectoris [transl. by C. A. Williams]. PMID- 20296164 TI - The protection of the homeopathic practitioner in his rights as a physician. PMID- 20296166 TI - Synopsis of the investigation of twenty homeopathic remedies. PMID- 20296167 TI - Acute and chronic hepatitis. PMID- 20296168 TI - Malaria. PMID- 20296169 TI - X-ray potencies. PMID- 20296170 TI - Practical steps in homeopathic postgraduate education. PMID- 20296172 TI - The necessity for homeopathic postgraduate education. PMID- 20296171 TI - Postgraduate homeopathic education on the Pacific Coast. PMID- 20296173 TI - The founding and development of osteopathy as I recall it. PMID- 20296174 TI - The principles of osteopathy as I practice them. PMID- 20296175 TI - Muscle tone and its significance. PMID- 20296176 TI - Obstetric technic. PMID- 20296177 TI - Osteopathy unlimited. PMID- 20296178 TI - Osteopathy's place in the therapeutic world. PMID- 20296179 TI - What an osteopathic lesion means to me. PMID- 20296180 TI - Osteopathic lesions and their effects. PMID- 20296181 TI - Some clinical observations relative to lesions of the lumbo-sacro-iliac area. PMID- 20296182 TI - Head's law and its relation to treatment of the viscera. PMID- 20296183 TI - Seminar discussion of infantile paralysis. PMID- 20296184 TI - Important phases in the treatment of infantile paralysis. PMID- 20296185 TI - A theory on the source of infantile paralysis virus. PMID- 20296186 TI - Cranial osteopathy. PMID- 20296187 TI - Acute anterior poliomyelitis. PMID- 20296188 TI - Post polio paralysis. PMID- 20296189 TI - Cranial treatment in acute conditions. PMID- 20296190 TI - Reflexes. PMID- 20296191 TI - Definition of osteopathy. PMID- 20296192 TI - Second dorsal lesion a causative factor in epilepsy. PMID- 20296193 TI - The osteopathic treatment for lobar pneumonia. PMID- 20296194 TI - Rheumatic fever. PMID- 20296195 TI - Liver and gall bladder technic. PMID- 20296196 TI - McCole's technic for treatment of osteopathic lesions of the sacroiliac articulation. PMID- 20296197 TI - Four hand technic for slight operators. PMID- 20296198 TI - A self-applied method for securing passive movement in each vertebral joint. PMID- 20296199 TI - Who would pay the bill? PMID- 20296200 TI - Plan for an integrated hospital. PMID- 20296201 TI - For current medical records. PMID- 20296202 TI - Hospitals' new role as Michigan decentralizes. PMID- 20296203 TI - Some problems encountered in caring exclusively for chronic disease patients. PMID- 20296204 TI - Ten-year report on service and costs in seven small hospitals. PMID- 20296205 TI - Simplified techniques for preparing infant formulas. PMID- 20296206 TI - The technique of leadership. PMID- 20296207 TI - Intravenous therapy is work for nurse specialists. PMID- 20296208 TI - A psychiatric ward for diagnosis service and short term care. PMID- 20296210 TI - Sweden moves toward free care for all. PMID- 20296209 TI - What will microfilming records cost the hospital? PMID- 20296211 TI - Put the pharmacy in a central location. PMID- 20296212 TI - Flexibility; basic nursing unit for hospitals over 50 beds. PMID- 20296213 TI - An expanded service through biological photography. PMID- 20296214 TI - HOW MANY closed beds? PMID- 20296216 TI - CRUSADE underway to aid nation's spastic children. PMID- 20296215 TI - Hospitals and health departments. PMID- 20296217 TI - The appearance of sheep cell lysins and human A cell agglutinins in a rabbit immunized with a partially purified blood group A-specific substance from hog gastric mucin. PMID- 20296218 TI - Bacterial warfare, a critical analysis of the available agents, their possible military applications, and the means for protection against them. PMID- 20296219 TI - National differences in creativity. PMID- 20296220 TI - Intelligentsia of China. PMID- 20296221 TI - How many Negroes pass? PMID- 20296222 TI - The sex lives of unmarried men. PMID- 20296223 TI - Experiments in testing for leadership. PMID- 20296224 TI - The toxicology of the newer metals. PMID- 20296225 TI - Poisoning of firemen by irritant fumes; cadmium and sulphonated castor oil. PMID- 20296226 TI - The transfer of heat through sun helmets. PMID- 20296227 TI - An experiment on the use of psychological tests as an aid to the rehabilitation of hospital patients. PMID- 20296228 TI - Acute paranitraniline poisoning. PMID- 20296229 TI - The occupational hazard of DDT spraying. PMID- 20296230 TI - Oleogranuloma; the late effects of accidental injection of mineral oil under pressure. PMID- 20296231 TI - Calcium necrosis of the skin. PMID- 20296232 TI - Absenteeism and separation in relation to length of employment. PMID- 20296233 TI - Traumatic heart conditions. PMID- 20296234 TI - Medical records. PMID- 20296235 TI - Cold wave dermatitis; report of two cases. PMID- 20296237 TI - Refrigeration in surgery. PMID- 20296236 TI - Scrotal swellings in industrial practice. PMID- 20296238 TI - Lung changes associated with the manufacture of alumina abrasives. PMID- 20296239 TI - Some experiences with polarographic methods in controlling a lead hazard in brass foundries. PMID- 20296240 TI - The simultaneous determination of lead and zinc in atmospheric samples; a polarographic method utilizing a double internal standard. PMID- 20296241 TI - Cryolite as a detoxifying agent for lead arsenate on plants and animals. PMID- 20296242 TI - A comparative study of the lead content of street dirts in New York City in 1924 and 1934. PMID- 20296244 TI - The acute and chronic toxicity of methyl chloride; hematology and biochemical studies. PMID- 20296243 TI - Effect of protein and carbohydrate intake on liver injury produced in dogs by carbon tetrachloride. PMID- 20296245 TI - Acute toxicity and general systemic actions of diethylene glycol monoethyl ether (carbitol). PMID- 20296246 TI - Radioactive emanations; their nature, mechanism of action, biological effects and tolerance limits. PMID- 20296247 TI - Some management views on our medical program. PMID- 20296248 TI - The producer needs a doctor. PMID- 20296249 TI - Impact of social security on company plans and medical services. PMID- 20296250 TI - Medical aid for foreign marketing affiliates. PMID- 20296251 TI - Medical service in the domestic marketing field. PMID- 20296252 TI - The seven phases of our medical service. PMID- 20296253 TI - Purpose and objectives of the Medical Research Department. PMID- 20296255 TI - Marine medical service. PMID- 20296254 TI - Domestic medical service. PMID- 20296256 TI - Hospital organization. PMID- 20296257 TI - Establishment and maintenance of training school for nurses in South America. PMID- 20296258 TI - Hospital standards required by the American College of Surgeons. PMID- 20296259 TI - England during the war. PMID- 20296260 TI - Experiences as a Japanese prisoner. PMID- 20296261 TI - Constructive medicine; the answer to industry's medical problem. PMID- 20296262 TI - Public health problems in tropical industry. PMID- 20296263 TI - Early diagnosis and treatment of tuberculosis. PMID- 20296264 TI - Rickettsia-produced exanthematic typhus diseases in Colombia. PMID- 20296265 TI - Control of amebiasis. PMID- 20296266 TI - Abdominal emergencies. PMID- 20296267 TI - Medical care and preventive medicine as applied to isolated communities. PMID- 20296268 TI - Methods of sanitation and preventive medicine used in wildcat camps in Ecuador. PMID- 20296269 TI - History of malaria in Venezuela. PMID- 20296270 TI - Diagnosis of heart disease. PMID- 20296271 TI - Modern therapeutic trends in heart disease. PMID- 20296272 TI - Rehabilitation of the physically unfit. PMID- 20296273 TI - Diagnosis and therapy of diarrhea. PMID- 20296274 TI - Medical aspects of the treatment of peptic ulcer. PMID- 20296275 TI - Surgical aspects of the treatment of peptic ulcer. PMID- 20296276 TI - Sulfonamides and antibiotics in the treatment of surgical infections. PMID- 20296277 TI - Present status of antibacterial agents in the treatment of systemic infection. PMID- 20296278 TI - Fractures of the spine. PMID- 20296279 TI - Treatment of burns. PMID- 20296280 TI - Common preventable diseases in Cuba. PMID- 20296281 TI - Advances in the treatment of venereal diseases. PMID- 20296282 TI - Common eye conditions encountered in tropical employees. PMID- 20296283 TI - Sensitivity to thiamine hydrochloride, review of the literature and report of a case. PMID- 20296284 TI - Considerations in the prevention of tuberculosis. PMID- 20296286 TI - The Pestalozzi village at Trogen, Switzerland [transl. L. Forrester]. PMID- 20296285 TI - Experiences of ten years' work at a municipal contraceptive clinic. PMID- 20296287 TI - Training sightless veterans for precision work. PMID- 20296288 TI - Recent state legislation concerning prepayment medical care. PMID- 20296289 TI - [Joint action of cardiology centers and corporate organization Portuguese to aid your chances of heart patients]. PMID- 20296290 TI - [The miracle and science]. PMID- 20296291 TI - [Doctrines, aspirations and trends]. PMID- 20296292 TI - [The Center for social welfare assistance]. PMID- 20296293 TI - [A children's hospital]. PMID- 20296294 TI - [To marry or not marry]. PMID- 20296295 TI - [Address to the Pontifical Academy of Sciences]. PMID- 20296296 TI - [Not Available]. PMID- 20296297 TI - [Not Available]. PMID- 20296298 TI - [Not Available]. PMID- 20296299 TI - [Not Available]. PMID- 20296300 TI - [Not Available]. PMID- 20296301 TI - [Not Available]. PMID- 20296302 TI - [Not Available]. PMID- 20296303 TI - [Not Available]. PMID- 20296305 TI - [Not Available]. PMID- 20296304 TI - [Not Available]. PMID- 20296306 TI - [Not Available]. PMID- 20296307 TI - [Not Available]. PMID- 20296308 TI - [Not Available]. PMID- 20296309 TI - [Not Available]. PMID- 20296310 TI - [Not Available]. PMID- 20296311 TI - [Not Available]. PMID- 20296312 TI - [Not Available]. PMID- 20296313 TI - [Not Available]. PMID- 20296314 TI - [Not Available]. PMID- 20296315 TI - [Not Available]. PMID- 20296316 TI - [Not Available]. PMID- 20296318 TI - [Not Available]. PMID- 20296317 TI - [Not Available]. PMID- 20296319 TI - [Not Available]. PMID- 20296320 TI - [Not Available]. PMID- 20296321 TI - [Not Available]. PMID- 20296322 TI - [Not Available]. PMID- 20296323 TI - [Not Available]. PMID- 20296324 TI - [Not Available]. PMID- 20296325 TI - [Not Available]. PMID- 20296326 TI - [Not Available]. PMID- 20296327 TI - [Not Available]. PMID- 20296328 TI - [Not Available]. PMID- 20296329 TI - [Not Available]. PMID- 20296330 TI - [Not Available]. PMID- 20296331 TI - [Not Available]. PMID- 20296332 TI - [Not Available]. PMID- 20296333 TI - [Not Available]. PMID- 20296334 TI - [Not Available]. PMID- 20296335 TI - [Not Available]. PMID- 20296336 TI - [Not Available]. PMID- 20296337 TI - [Not Available]. PMID- 20296338 TI - [Not Available]. PMID- 20296339 TI - [Not Available]. PMID- 20296340 TI - [Not Available]. PMID- 20296341 TI - [Not Available]. PMID- 20296342 TI - Study of cases of coronary thrombosis with myocardial infarction in Rochester hospitals 1940-1944. PMID- 20296343 TI - Speech correction in the Rochester, New York schools. PMID- 20296345 TI - Physical medicine. PMID- 20296344 TI - The life and works of Sir James Young Simpson. PMID- 20296346 TI - Colitis. PMID- 20296347 TI - Streptomycin; the indications, contraindications, mode of administration, dosage and toxic effects. PMID- 20296348 TI - The treatment of malaria. PMID- 20296349 TI - The diagnosis of pulmonary tuberculosis. PMID- 20296350 TI - The treatment of pulmonary tuberculosis. PMID- 20296351 TI - Some injuries to the knee joint. PMID- 20296352 TI - Some injuries to the wrist and ankle. PMID- 20296353 TI - Pernicious anaemia. PMID- 20296354 TI - The education of the medical and allied professions in rheumatic fever and rheumatic heart disease. PMID- 20296355 TI - A report of five upper respiratory infection epidemics at St. Francis, 1944-1946. PMID- 20296356 TI - TENTH anniversary of St. Francis Sanatorium for Cardiac Children, Roslyn, L. I. PMID- 20296357 TI - Sigmodal in obstetrics; clinical observations with a report of three reactions. PMID- 20296358 TI - Acute puerperal inversion of the uterus; with two cases seen at cesarean section. PMID- 20296359 TI - Plastic repair of deformity of penis due to granuloma inguinale. PMID- 20296360 TI - Newer phases of gastroduodenal ulcer. PMID- 20296361 TI - [Not Available]. PMID- 20296362 TI - Rheumatic fever from the patient's point of view. PMID- 20296363 TI - Prisons are outmoded. PMID- 20296364 TI - The centennium of anaesthesia. PMID- 20296366 TI - Triweekly arsenotherapy a safe and effective ambulatory treatment regimen for early syphilis. PMID- 20296365 TI - Post war training in surgery. PMID- 20296367 TI - Toxic reactions of penicillin. PMID- 20296368 TI - [Primary carcinoma of body and tail of pancreas with tumor necrosis]. PMID- 20296369 TI - The kidney and kidney function tests; the phenolsulfonephthalein test. PMID- 20296370 TI - [Not Available]. PMID- 20296371 TI - [Not Available]. PMID- 20296372 TI - Pigmentations faciales. PMID- 20296373 TI - [Not Available]. PMID- 20296374 TI - [Not Available]. PMID- 20296375 TI - [Not Available]. PMID- 20296376 TI - [Not Available]. PMID- 20296377 TI - [Not Available]. PMID- 20296378 TI - [Not Available]. PMID- 20296379 TI - [Not Available]. PMID- 20296380 TI - [Not Available]. PMID- 20296381 TI - [Not Available]. PMID- 20296382 TI - [Not Available]. PMID- 20296383 TI - Periarteritis nodosa; a case requiring surgery, with a review of the literature. PMID- 20296384 TI - Intussusception; case report. PMID- 20296385 TI - Krukenberg tumors. PMID- 20296387 TI - The Iowa doctor one hundred years ago. PMID- 20296386 TI - METOPON hydrochloride (methyldihydromorphinone hydrochloride). PMID- 20296388 TI - Allergic rhinitis; latest development in its treatment. PMID- 20296389 TI - Pernicious anemia. PMID- 20296390 TI - Venereal disease; its diagnosis and treatment. PMID- 20296391 TI - Atomic energy in medicine. PMID- 20296393 TI - Submucous lipoma of colon. PMID- 20296392 TI - X-ray in the diagnosis of abdominal aortic aneurysm. PMID- 20296394 TI - Radiation therapy for cutaneous hemangiomas. PMID- 20296395 TI - Pseudomucinous cystadenocarcinoma of the ovary; case report. PMID- 20296396 TI - Radiation therapy of ovarian tumors. PMID- 20296397 TI - The reciprocal relation between lung function and the pituitary gland. PMID- 20296398 TI - Pulmonary resection for tuberculosis. PMID- 20296399 TI - Bronchoscopic diagnosis in nontuberculosis chest conditions. PMID- 20296400 TI - The immunological factor involved in a case of hemolytic disease of the newborn. PMID- 20296401 TI - Congenital heart disease. PMID- 20296403 TI - [Not Available]. PMID- 20296402 TI - [Not Available]. PMID- 20296404 TI - [Not Available]. PMID- 20296405 TI - [Not Available]. PMID- 20296406 TI - [Not Available]. PMID- 20296407 TI - [Not Available]. PMID- 20296408 TI - [Not Available]. PMID- 20296409 TI - [Not Available]. PMID- 20296410 TI - The use of isotopes in medical research. PMID- 20296411 TI - Roentgenologic contribution to the diagnosis of functional intestinal disorders. PMID- 20296412 TI - Treatment of intestinal conditions as based on disordered function. PMID- 20296413 TI - Benign strictures of the biliary ducts. PMID- 20296415 TI - Herpes zoster appearing after trauma. PMID- 20296414 TI - Appraisal of surgery in the treatment of bronchiectasis. PMID- 20296416 TI - The place of health resort therapy in dermatologic disorders. PMID- 20296417 TI - Paroxysmal hypertension from pheochromocytomas. PMID- 20296418 TI - MEDICAL LICENSURE statistics for 1946. PMID- 20296419 TI - Methods of securing and maintaining adequate resources for the care of the chronically-ill. PMID- 20296420 TI - The blood clotting mechanism; clinical use of the anticoagulants. PMID- 20296421 TI - Tropical medicine; malaria. PMID- 20296422 TI - Hunger and its pathological effects in Holland. PMID- 20296423 TI - The pituitary-ovarian relationship. PMID- 20296425 TI - Diagnosis of acute abdomen. PMID- 20296424 TI - Rheumatic fever in childhood. PMID- 20296426 TI - Diffuse vascular diseases; disseminated lupus erythematosus. PMID- 20296427 TI - Surgical lesions of the neck; some aspects of their diagnosis and management. PMID- 20296428 TI - A preliminary review of poliomyelitis in Florida. PMID- 20296429 TI - Indications for tracheotomy. PMID- 20296430 TI - Penicillin in the treatment of diphtheria; a preliminary note. PMID- 20296431 TI - Subacute bacterial endocarditis with treatment of two cases with penicillin. PMID- 20296432 TI - The nutrition problem in the Punjab. PMID- 20296433 TI - Treatment of relapsing cases of malaria. PMID- 20296434 TI - Plasma transfusion. PMID- 20296435 TI - Ointments. PMID- 20296436 TI - Paralysis of abdominal and spinal muscles in poliomyelitis. PMID- 20296437 TI - The surgical treatment of pilonidal cysts and sinuses. PMID- 20296438 TI - High lights on malaria. PMID- 20296439 TI - [Primary carcinoma of the submaxillary gland, involving the mandible by direct extension, and with multiple metastases]. PMID- 20296440 TI - Mechanism of the thymol turbidity test. PMID- 20296441 TI - A study of the serum biliverdin concentration in various types of jaundice. PMID- 20296442 TI - Differential agglutination of human erythrocytes; evaluation of technique. PMID- 20296443 TI - Fibrinogen deficiency; clinical features and probable etiologic factors. PMID- 20296444 TI - Biochemical studies during malarial and artificial fevers. PMID- 20296445 TI - Normal sedimentation rates in active pulmonary tuberculosis; a study of 1,066 cases in a naval tuberculosis center. PMID- 20296446 TI - Effect of 3,3' methylenebis (4-hydroxycoumarin) on vitamin A deficient ducks. PMID- 20296447 TI - Some factors affecting the susceptibility of rats to various barbiturates; the effect of age and sex. PMID- 20296448 TI - A simplification of the serologic diagnosis of Salmonella cultures. PMID- 20296449 TI - The prothrombin time and variables in the method. PMID- 20296450 TI - A method for counting bacteria in the nasal cavity; application of the method in demonstrating the action of intranasal penicillin administration. PMID- 20296451 TI - A modified technique for the differentiation of pneumococci from alpha hemolytic streptococci using sodium desoxycholate. PMID- 20296452 TI - A simple apparatus for culturing Neisseria gonorrhea under partial carbon dioxide tension. PMID- 20296453 TI - A test fluid for control of the gold reaction. PMID- 20296454 TI - The epidemiology of streptococcal infections. PMID- 20296455 TI - Exchange transfusion; a new method of treatment for erythroblastosis fetalis. PMID- 20296456 TI - The quantitative aspects of fluid therapy in infants and children. PMID- 20296457 TI - Hypoglycemia associated with hyperplasia of the islets of Langerhans; report of a case successfully treated by surgery. PMID- 20296459 TI - Tracheotomy in bulbar poliomyelitis. PMID- 20296458 TI - Acute intussusception in infancy and early childhood with a review of 55 consecutive cases. PMID- 20296460 TI - Nutritional and psychological aspects of the care of patients with bulbar poliomyelitis. PMID- 20296461 TI - Observations on a poliomyelitis outbreak in North Dakota in 1946; with special consideration of spinal fluid findings. PMID- 20296462 TI - Apparatus for the relief of acute obstructive laryngitis; treatment of a fulminating case due to H. influenzae. PMID- 20296463 TI - Unusual causes of hematuria in infants and children. PMID- 20296464 TI - Paroxysmal tachycardia in infancy. PMID- 20296465 TI - Menopause syndrome. PMID- 20296466 TI - Medicine and national security. PMID- 20296467 TI - Neurosurgical relief of intractable pain. PMID- 20296468 TI - [Acute poliomyelitis, bulbar type]. PMID- 20296469 TI - The discovery of the cause of malaria. PMID- 20296470 TI - Some present day problems affecting milk quality. PMID- 20296471 TI - CANCER program in New Jersey; a statewide tissue diagnostic service. PMID- 20296472 TI - Ambulatory electric shock treatment. PMID- 20296473 TI - Scleroderma treated with promin, with report of a case. PMID- 20296474 TI - Acute osteomyelitis of the cervical spine with probable epidural infection; report of cure with penicillin therapy. PMID- 20296475 TI - The operation of public law 725; Hospital Survey and Construction Act. PMID- 20296476 TI - Cardiac complaints and chronic nonspecific prostatitis. PMID- 20296477 TI - Treatment of hyperthyroidism; present status. PMID- 20296478 TI - Paralysis of the larynx. PMID- 20296479 TI - Determination of unmet need for medical attention among Michigan farm families. PMID- 20296480 TI - Functional bleeding at different age periods; significance and management. PMID- 20296482 TI - Paratyphoid fever. PMID- 20296481 TI - Functional hyperinsulinism; a common and well-defined clinical entity amenable to medical management. PMID- 20296483 TI - Modern trends in urology. PMID- 20296484 TI - Local instillation of penicillin in chronic suppurative maxillary sinusitis. PMID- 20296485 TI - Ocular war injuries. PMID- 20296486 TI - Simplified artificial infant feeding. PMID- 20296487 TI - Transurethral resection in the treatment for prostatic median bar. PMID- 20296488 TI - The management of prolapse of the uterus. PMID- 20296489 TI - Epidermoid carcinoma of the vulva; radical vulvectomy. PMID- 20296490 TI - Is hypoproteinemia the cause of the toxemias of pregnancy? PMID- 20296491 TI - Hiccough. PMID- 20296492 TI - Gunshot wounds of the extraperitoneal rectum. PMID- 20296494 TI - Hypoglycemia; report of a case. PMID- 20296493 TI - Treatment of some common skin disorders in children. PMID- 20296495 TI - [Multipara with a polyhydramnios associated with a fetus whose cranium was grossly deformed]. PMID- 20296496 TI - The management of acute head injuries. PMID- 20296497 TI - Surgery of infancy and childhood. PMID- 20296498 TI - The treatment of goiter. PMID- 20296499 TI - Trends of irradiation therapy in ophthalmology, laryngology, and with radioactive isotopes, with a review of the literature. PMID- 20296500 TI - Recent trends in x-ray therapy with particular reference to supervoltage x-rays. PMID- 20296501 TI - Clinical indications for X-ray and radium therapy. PMID- 20296502 TI - Diphtheria in Kentucky. PMID- 20296503 TI - [Not Available]. PMID- 20296504 TI - [Not Available]. PMID- 20296505 TI - [Not Available]. PMID- 20296506 TI - [Not Available]. PMID- 20296507 TI - [Not Available]. PMID- 20296508 TI - [Not Available]. PMID- 20296509 TI - [Not Available]. PMID- 20296510 TI - [Not Available]. PMID- 20296511 TI - [Not Available]. PMID- 20296512 TI - [Not Available]. PMID- 20296513 TI - [Not Available]. PMID- 20296514 TI - Surgical handicraft. PMID- 20296515 TI - Survival of variola virus in dried exudate and crusts from smallpox patients. PMID- 20296516 TI - Sonne dysentery and non-specific gastro-enteritis in a hospital. PMID- 20296517 TI - Diagnosis of epilepsy in service cases. PMID- 20296518 TI - Therapeutic uses of khellin; method of standardisation. PMID- 20296519 TI - New concepts of hospital feeding; hospital nutrition programme of the Canadian Army Overseas. PMID- 20296520 TI - Tuberculosis and the National Health Service Act. PMID- 20296521 TI - PROCAINE and cocaine; a name misheard. PMID- 20296522 TI - Peritoneal dialysis. PMID- 20296523 TI - Compression of median nerve in carpal tunnel. PMID- 20296524 TI - Mr. Jacob Mountgarret, R. N., the pioneer surgeon of Van Diemen's Land, 1803 1828. PMID- 20296525 TI - The beneficial effects of yeast in diabetes mellitus. PMID- 20296526 TI - Anaesthesia for upper abdominal surgery. PMID- 20296527 TI - A precautionary measure advisable in certain endurance tests. PMID- 20296528 TI - Trial labour. PMID- 20296529 TI - The treatment of acute perforation in peptic ulcers. PMID- 20296530 TI - Must syphilis still serve? PMID- 20296531 TI - Recent observations on uric acid. PMID- 20296532 TI - Cancer statistics from the Royal Prince Alfred Hospital, Sydney. PMID- 20296533 TI - Nutrition survey of Tasmania; food consumption and dietary levels in the spring of 1945. PMID- 20296534 TI - A note on the Durham fermentation tube. PMID- 20296535 TI - Carcinoma of the sigmoid colon removed four years after diagnosis. PMID- 20296536 TI - Addison's disease. PMID- 20296537 TI - The zoological position of man. PMID- 20296538 TI - The value of the cold pressor test in the prediction of hypertension and toxaemia in pregnancy. PMID- 20296539 TI - Undergraduate and post-graduate education in physical medicine. PMID- 20296540 TI - Cross-infection of wounds in a surgical ward during a trial of the use of oiled blankets. PMID- 20296541 TI - Nutritional deficiency diseases. PMID- 20296542 TI - Note on a case of bilateral Dupuytren's contracture occurring in association with spondylitis ankylopoietica. PMID- 20296544 TI - Peptic ulcer. PMID- 20296543 TI - Patent ductus arteriosus. PMID- 20296545 TI - [Not Available]. PMID- 20296546 TI - [Not Available]. PMID- 20296547 TI - [Not Available]. PMID- 20296548 TI - [Not Available]. PMID- 20296549 TI - [Not Available]. PMID- 20296550 TI - [Not Available]. PMID- 20296551 TI - [Not Available]. PMID- 20296552 TI - [Not Available]. PMID- 20296553 TI - [Not Available]. PMID- 20296554 TI - [Not Available]. PMID- 20296555 TI - [Not Available]. PMID- 20296556 TI - [Not Available]. PMID- 20296557 TI - [Not Available]. PMID- 20296559 TI - [Not Available]. PMID- 20296558 TI - [Not Available]. PMID- 20296560 TI - [Not Available]. PMID- 20296561 TI - [Not Available]. PMID- 20296562 TI - [Not Available]. PMID- 20296563 TI - [Not Available]. PMID- 20296565 TI - [Not Available]. PMID- 20296564 TI - [Not Available]. PMID- 20296566 TI - [Not Available]. PMID- 20296567 TI - [Not Available]. PMID- 20296569 TI - [Not Available]. PMID- 20296568 TI - [Not Available]. PMID- 20296570 TI - [Not Available]. PMID- 20296571 TI - The diagnosis and treatment of chronic nasal sinusitis in children. PMID- 20296572 TI - Population and recent trends in vital rates. PMID- 20296573 TI - Endometriosis; diagnosis and treatment. PMID- 20296574 TI - The value of X-rays in dentistry. PMID- 20296575 TI - Inhibitory factors in the postwar world. PMID- 20296576 TI - Carcinoma of the bronchus. PMID- 20296577 TI - The social problem of high-grade deficiency. PMID- 20296578 TI - Tuberculous epididymo-orchitis. PMID- 20296579 TI - Treatment of rodent ulcer by injections of methylene blue and hydrogen peroxide. PMID- 20296580 TI - Modern treatment of bronchiectasis in childhood. PMID- 20296581 TI - Surgery of the hand and fingers; injuries and infections. PMID- 20296582 TI - The diagnosis and treatment of spastic colon. PMID- 20296583 TI - The Disabled Persons (employment) Act, 1944. PMID- 20296584 TI - Spas. PMID- 20296585 TI - Injuries round the knee joint. PMID- 20296586 TI - The prognosis and treatment of psychiatric sequelae of head injuries. PMID- 20296587 TI - The value of drugs in the treatment of peptic ulcer. PMID- 20296588 TI - Prevention and treatment of abortion. PMID- 20296589 TI - The significance and modern treatment of haemoptysis. PMID- 20296590 TI - The carrier problem in disease. PMID- 20296591 TI - Surgery under difficulties. PMID- 20296592 TI - Autoserotherapy for the treatment of drug addiction. PMID- 20296593 TI - Some reflections on the clinical examination of the chest. PMID- 20296594 TI - Recent advances in the surgery of the pancreas. PMID- 20296595 TI - Sprains of the ankle. PMID- 20296596 TI - The prevention and treatment of travel sickness. PMID- 20296597 TI - [Not Available]. PMID- 20296598 TI - [Not Available]. PMID- 20296599 TI - Benign and malignant tumors of the small intestine. PMID- 20296600 TI - Vasomotor disturbances in poliomyelitis, with special reference to treatment with paravertebral sympathetic block. PMID- 20296601 TI - An eruptive fever involving the skin and mucous membranes (Stevens-Johnson disease). PMID- 20296602 TI - Streptomycin; bacteriologic and pharmacologic aspects. PMID- 20296603 TI - [Hemoglobinuric nephrosis]. PMID- 20296604 TI - [Adenoacanthoma of cardia of stomach]. PMID- 20296605 TI - Bacterial endocarditis treated with penicillin; observations in nine cases. PMID- 20296606 TI - Persistence of remissions of thyrotoxicosis after cessation of thiouracil therapy. PMID- 20296607 TI - Acute brucellosis among laboratory workers. PMID- 20296608 TI - Streptomycin; clinical uses. PMID- 20296609 TI - [Adenocarcinoma of jejunum]. PMID- 20296611 TI - The management of acute arterial occlusions. PMID- 20296610 TI - [Gallstone ileus]. PMID- 20296612 TI - The future's demands upon the hospital. PMID- 20296613 TI - Modern concepts of neurosurgical treatment of herniated nucleus pulposus. PMID- 20296615 TI - Safety factors in surgery of the colon. PMID- 20296614 TI - Effects of thrombin injection into hematoma enveloping fractures of humerus in rabbits. PMID- 20296616 TI - Sutures, wound healing and early ambulation. PMID- 20296617 TI - Surgical correction of ptosis. PMID- 20296618 TI - Malignant melanoma of the choroid. PMID- 20296619 TI - What can be done for conduction deafness. PMID- 20296620 TI - Tridione; its use in treatment of epilepsy and other neurologic disorders. PMID- 20296621 TI - The diagnosis of nervous diseases. PMID- 20296622 TI - The diagnosis of enlargement of the lymphatic glands. PMID- 20296623 TI - The diagnosis, prognosis and symptomatic treatment of carcinoma of the stomach. PMID- 20296624 TI - Sarcoidosis. PMID- 20296625 TI - Surgical aspects of spinal conditions. PMID- 20296626 TI - The comparative biology of anxiety. PMID- 20296627 TI - Common fungus infections of the skin. PMID- 20296628 TI - Spontaneous closure of post-irradiation vesico-vaginal fistula; case report. PMID- 20296629 TI - Symposium on tetralogy of Fallot. PMID- 20296630 TI - Basis of cyanosis in tetralogy of Fallot. PMID- 20296631 TI - Pathologic and embryologic considerations in tetralogy of Fallot. PMID- 20296632 TI - Classic clinical features of tetralogy of Fallot. PMID- 20296634 TI - Differential diagnosis of tetralogy of Fallot. PMID- 20296633 TI - Roentgenologic diagnosis of tetralogy of Fallot. PMID- 20296635 TI - Surgical considerations in tetralogy of Fallot. PMID- 20296636 TI - Congenital hemivertebrata in the cervical region with brachial neuritis; report of case. PMID- 20296637 TI - Some ophthalmological conditions in colour transparencies. PMID- 20296638 TI - Onyalai. PMID- 20296639 TI - A case of onyalai. PMID- 20296640 TI - A case of diabetes mellitus. PMID- 20296641 TI - A case of lung abscess. PMID- 20296642 TI - A case of amoebic pericolic abscess. PMID- 20296643 TI - Observations on the local treatment of burns. PMID- 20296644 TI - Brucellosis conference. PMID- 20296645 TI - Autopsy report; sudden death in a 54 year old farmer suffering from draining sinuses on the neck of 15 months duration. PMID- 20296646 TI - Appendicitis with pre-existing chronic nephritis. PMID- 20296647 TI - Case of empyema of the chest with medical treatment. PMID- 20296648 TI - Lingual thyroid. PMID- 20296649 TI - Possible Paget's disease of the vulva. PMID- 20296650 TI - Subacute bacterial endocarditis. PMID- 20296651 TI - Subdural hydroma. PMID- 20296652 TI - Hunger oedema. PMID- 20296653 TI - The oedematous syndrome of nephritis with special reference to prognosis. PMID- 20296654 TI - Osteomalacia with Looser's nodes (Milkman's syndrome) due to a raised resistance to vitamin D acquired about the age of 15 years. PMID- 20296655 TI - The Army Medical Department in World War II. PMID- 20296656 TI - The treatment of arterial hypertension. PMID- 20296657 TI - A psychiatrist's reflections on mental hygiene. PMID- 20296658 TI - Warriors against disease. PMID- 20296659 TI - [Not Available]. PMID- 20296660 TI - [Not Available]. PMID- 20296661 TI - [Not Available]. PMID- 20296662 TI - [Not Available]. PMID- 20296663 TI - [Not Available]. PMID- 20296664 TI - [Not Available]. PMID- 20296665 TI - [Not Available]. PMID- 20296666 TI - [Not Available]. PMID- 20296667 TI - [Not Available]. PMID- 20296668 TI - [Not Available]. PMID- 20296669 TI - [Not Available]. PMID- 20296670 TI - [Not Available]. PMID- 20296672 TI - [Not Available]. PMID- 20296671 TI - [Not Available]. PMID- 20296673 TI - [Not Available]. PMID- 20296674 TI - Penicillin; its development for use in the clinic. PMID- 20296675 TI - The medical care of the veteran. PMID- 20296676 TI - The differential diagnosis and treatment of neuralgia of the face. PMID- 20296677 TI - Newer developments in the pathogenesis and treatment of hypertension. PMID- 20296678 TI - The value of the stained vaginal smear in gynecological diagnosis. PMID- 20296679 TI - Relationship and practical application of the Rh and Hr factors. PMID- 20296680 TI - Torsion of ovarian pedicle in a two-year-old child. PMID- 20296681 TI - The localization of myocardial infarcts with particular reference to lateral infarction and to the T1Q111 pattern. PMID- 20296682 TI - [Not Available]. PMID- 20296683 TI - [Not Available]. PMID- 20296684 TI - [Not Available]. PMID- 20296685 TI - [Not Available]. PMID- 20296686 TI - [Not Available]. PMID- 20296687 TI - [Not Available]. PMID- 20296688 TI - [Not Available]. PMID- 20296689 TI - [Not Available]. PMID- 20296690 TI - [Not Available]. PMID- 20296691 TI - [Not Available]. PMID- 20296692 TI - [Not Available]. PMID- 20296693 TI - [Not Available]. PMID- 20296694 TI - [Not Available]. PMID- 20296695 TI - [Not Available]. PMID- 20296697 TI - [Not Available]. PMID- 20296696 TI - [Not Available]. PMID- 20296698 TI - [Not Available]. PMID- 20296699 TI - [Not Available]. PMID- 20296700 TI - [Not Available]. PMID- 20296701 TI - [Not Available]. PMID- 20296702 TI - [Not Available]. PMID- 20296703 TI - [Not Available]. PMID- 20296704 TI - [Not Available]. PMID- 20296705 TI - [Not Available]. PMID- 20296706 TI - [Not Available]. PMID- 20296707 TI - [Not Available]. PMID- 20296708 TI - [Not Available]. PMID- 20296709 TI - [Not Available]. PMID- 20296710 TI - [Not Available]. PMID- 20296711 TI - [Not Available]. PMID- 20296713 TI - [Not Available]. PMID- 20296712 TI - [Not Available]. PMID- 20296714 TI - [Not Available]. PMID- 20296715 TI - [Not Available]. PMID- 20296716 TI - [Not Available]. PMID- 20296717 TI - [Not Available]. PMID- 20296718 TI - [Not Available]. PMID- 20296719 TI - [Not Available]. PMID- 20296720 TI - [Not Available]. PMID- 20296721 TI - [Not Available]. PMID- 20296722 TI - [Not Available]. PMID- 20296723 TI - [Not Available]. PMID- 20296724 TI - [Not Available]. PMID- 20296725 TI - [Not Available]. PMID- 20296726 TI - [Not Available]. PMID- 20296727 TI - [Not Available]. PMID- 20296728 TI - [Not Available]. PMID- 20296730 TI - [Not Available]. PMID- 20296729 TI - [Not Available]. PMID- 20296731 TI - [Not Available]. PMID- 20296732 TI - [Not Available]. PMID- 20296733 TI - [Not Available]. PMID- 20296735 TI - [Not Available]. PMID- 20296734 TI - [Not Available]. PMID- 20296736 TI - [Not Available]. PMID- 20296737 TI - [Not Available]. PMID- 20296738 TI - [Not Available]. PMID- 20296739 TI - [Not Available]. PMID- 20296740 TI - Studies on d-lysergic acid + hydroxybutylamine-(2) (methergine). PMID- 20296741 TI - Comments on the biological standardization of digitalis. PMID- 20296742 TI - [Not Available]. PMID- 20296744 TI - [Not Available]. PMID- 20296743 TI - [Not Available]. PMID- 20296745 TI - Some aspects of the biochemistry and pharmacology of the heart. PMID- 20296746 TI - [Not Available]. PMID- 20296747 TI - [Not Available]. PMID- 20296748 TI - [Not Available]. PMID- 20296749 TI - [Not Available]. PMID- 20296750 TI - [Not Available]. PMID- 20296751 TI - [Not Available]. PMID- 20296752 TI - [Not Available]. PMID- 20296753 TI - [Not Available]. PMID- 20296754 TI - [Not Available]. PMID- 20296755 TI - [Not Available]. PMID- 20296756 TI - [Not Available]. PMID- 20296757 TI - [Not Available]. PMID- 20296758 TI - [Not Available]. PMID- 20296759 TI - [Not Available]. PMID- 20296760 TI - [Not Available]. PMID- 20296761 TI - [Not Available]. PMID- 20296763 TI - [Not Available]. PMID- 20296762 TI - [Not Available]. PMID- 20296764 TI - [Not Available]. PMID- 20296765 TI - [Not Available]. PMID- 20296766 TI - [Not Available]. PMID- 20296767 TI - [Not Available]. PMID- 20296768 TI - [Not Available]. PMID- 20296769 TI - [Not Available]. PMID- 20296771 TI - [Not Available]. PMID- 20296770 TI - [Not Available]. PMID- 20296772 TI - [Not Available]. PMID- 20296773 TI - [Not Available]. PMID- 20296774 TI - [Not Available]. PMID- 20296775 TI - [Not Available]. PMID- 20296776 TI - [Not Available]. PMID- 20296777 TI - [Not Available]. PMID- 20296778 TI - [Not Available]. PMID- 20296779 TI - [Not Available]. PMID- 20296780 TI - [Not Available]. PMID- 20296782 TI - [Not Available]. PMID- 20296781 TI - [Not Available]. PMID- 20296783 TI - [Not Available]. PMID- 20296784 TI - [Not Available]. PMID- 20296785 TI - [Not Available]. PMID- 20296786 TI - [Not Available]. PMID- 20296787 TI - [Not Available]. PMID- 20296788 TI - [Not Available]. PMID- 20296789 TI - [Not Available]. PMID- 20296790 TI - [Not Available]. PMID- 20296791 TI - [Not Available]. PMID- 20296792 TI - [Not Available]. PMID- 20296793 TI - [Not Available]. PMID- 20296794 TI - [Not Available]. PMID- 20296795 TI - [Not Available]. PMID- 20296796 TI - [Not Available]. PMID- 20296797 TI - [Not Available]. PMID- 20296798 TI - [Not Available]. PMID- 20296799 TI - [Not Available]. PMID- 20296800 TI - [Not Available]. PMID- 20296801 TI - [Not Available]. PMID- 20296802 TI - [Not Available]. PMID- 20296803 TI - [Not Available]. PMID- 20296804 TI - [Not Available]. PMID- 20296805 TI - [Not Available]. PMID- 20296806 TI - [Not Available]. PMID- 20296807 TI - [Not Available]. PMID- 20296808 TI - [Not Available]. PMID- 20296809 TI - [Not Available]. PMID- 20296810 TI - [Not Available]. PMID- 20296811 TI - [Not Available]. PMID- 20296813 TI - [Not Available]. PMID- 20296812 TI - [Not Available]. PMID- 20296814 TI - [Not Available]. PMID- 20296815 TI - [Not Available]. PMID- 20296816 TI - [Not Available]. PMID- 20296818 TI - [Not Available]. PMID- 20296817 TI - [Not Available]. PMID- 20296819 TI - [Not Available]. PMID- 20296820 TI - [Not Available]. PMID- 20296821 TI - [Not Available]. PMID- 20296822 TI - [Not Available]. PMID- 20296824 TI - [Not Available]. PMID- 20296823 TI - [Not Available]. PMID- 20296825 TI - [Not Available]. PMID- 20296826 TI - [Not Available]. PMID- 20296827 TI - [Not Available]. PMID- 20296828 TI - [Not Available]. PMID- 20296829 TI - [Not Available]. PMID- 20296830 TI - [Not Available]. PMID- 20296831 TI - [Not Available]. PMID- 20296832 TI - [Not Available]. PMID- 20296833 TI - [Not Available]. PMID- 20296834 TI - [Not Available]. PMID- 20296835 TI - [Not Available]. PMID- 20296836 TI - [Not Available]. PMID- 20296837 TI - [Not Available]. PMID- 20296838 TI - [Not Available]. PMID- 20296839 TI - [Not Available]. PMID- 20296840 TI - [Not Available]. PMID- 20296841 TI - [Not Available]. PMID- 20296842 TI - [Not Available]. PMID- 20296843 TI - [Not Available]. PMID- 20296844 TI - [Not Available]. PMID- 20296845 TI - [Not Available]. PMID- 20296846 TI - [Not Available]. PMID- 20296848 TI - [Not Available]. PMID- 20296847 TI - [Not Available]. PMID- 20296849 TI - [Not Available]. PMID- 20296850 TI - [Not Available]. PMID- 20296851 TI - [Not Available]. PMID- 20296852 TI - [Not Available]. PMID- 20296853 TI - [Not Available]. PMID- 20296854 TI - [Not Available]. PMID- 20296855 TI - [Not Available]. PMID- 20296856 TI - [Not Available]. PMID- 20296857 TI - [Not Available]. PMID- 20296858 TI - [Not Available]. PMID- 20296859 TI - [Not Available]. PMID- 20296860 TI - [Not Available]. PMID- 20296861 TI - [Not Available]. PMID- 20296862 TI - [Not Available]. PMID- 20296863 TI - [Not Available]. PMID- 20296864 TI - [Not Available]. PMID- 20296865 TI - [Not Available]. PMID- 20296867 TI - [Not Available]. PMID- 20296866 TI - [Not Available]. PMID- 20296868 TI - [Not Available]. PMID- 20296869 TI - [Not Available]. PMID- 20296870 TI - [Not Available]. PMID- 20296871 TI - [Not Available]. PMID- 20296872 TI - [Not Available]. PMID- 20296873 TI - [Not Available]. PMID- 20296874 TI - [Not Available]. PMID- 20296875 TI - [Not Available]. PMID- 20296876 TI - [Not Available]. PMID- 20296877 TI - [Not Available]. PMID- 20296878 TI - [Not Available]. PMID- 20296879 TI - [Not Available]. PMID- 20296880 TI - [Not Available]. PMID- 20296881 TI - [Not Available]. PMID- 20296882 TI - [Not Available]. PMID- 20296883 TI - [Not Available]. PMID- 20296884 TI - [Not Available]. PMID- 20296885 TI - [Not Available]. PMID- 20296886 TI - [Not Available]. PMID- 20296887 TI - [Not Available]. PMID- 20296888 TI - [Not Available]. PMID- 20296889 TI - [Not Available]. PMID- 20296890 TI - [Not Available]. PMID- 20296891 TI - [Not Available]. PMID- 20296892 TI - [Not Available]. PMID- 20296894 TI - [Not Available]. PMID- 20296893 TI - [Not Available]. PMID- 20296895 TI - [Not Available]. PMID- 20296896 TI - Chirurgie in USA. PMID- 20296897 TI - [Not Available]. PMID- 20296898 TI - [Not Available]. PMID- 20296899 TI - [Not Available]. PMID- 20296900 TI - [Not Available]. PMID- 20296901 TI - [Not Available]. PMID- 20296903 TI - [Not Available]. PMID- 20296902 TI - [Not Available]. PMID- 20296904 TI - [Not Available]. PMID- 20296905 TI - [Not Available]. PMID- 20296906 TI - [Not Available]. PMID- 20296907 TI - [Not Available]. PMID- 20296908 TI - [Not Available]. PMID- 20296909 TI - [Not Available]. PMID- 20296910 TI - [Not Available]. PMID- 20296911 TI - [Not Available]. PMID- 20296912 TI - [Not Available]. PMID- 20296913 TI - [Not Available]. PMID- 20296914 TI - [Not Available]. PMID- 20296915 TI - [Not Available]. PMID- 20296916 TI - [Not Available]. PMID- 20296917 TI - [Not Available]. PMID- 20296918 TI - [Not Available]. PMID- 20296919 TI - [Not Available]. PMID- 20296920 TI - Medical care and medical social service. PMID- 20296921 TI - Curare in anesthesia; with special reference to combined pentothal curare, nitrous oxide anesthesia. PMID- 20296922 TI - [Not Available]. PMID- 20296923 TI - [Not Available]. PMID- 20296924 TI - [Not Available]. PMID- 20296925 TI - [Not Available]. PMID- 20296926 TI - [Not Available]. PMID- 20296927 TI - [Not Available]. PMID- 20296928 TI - [Not Available]. PMID- 20296929 TI - [Not Available]. PMID- 20296930 TI - [Not Available]. PMID- 20296931 TI - [Not Available]. PMID- 20296932 TI - [Not Available]. PMID- 20296933 TI - [Not Available]. PMID- 20296934 TI - [Not Available]. PMID- 20296935 TI - [Not Available]. PMID- 20296936 TI - [Not Available]. PMID- 20296937 TI - [Not Available]. PMID- 20296938 TI - [Not Available]. PMID- 20296939 TI - [Not Available]. PMID- 20296940 TI - [Not Available]. PMID- 20296941 TI - [Not Available]. PMID- 20296942 TI - [Not Available]. PMID- 20296943 TI - [Not Available]. PMID- 20296944 TI - [Not Available]. PMID- 20296945 TI - [Not Available]. PMID- 20296946 TI - [Not Available]. PMID- 20296947 TI - [Not Available]. PMID- 20296948 TI - [Not Available]. PMID- 20296949 TI - [Not Available]. PMID- 20296950 TI - [Not Available]. PMID- 20296951 TI - [Not Available]. PMID- 20296952 TI - Folic acid (Lactobacillus casei faktor, bladsyre) ved behandling av anemier. PMID- 20296953 TI - [Not Available]. PMID- 20296954 TI - [Not Available]. PMID- 20296955 TI - [Not Available]. PMID- 20296956 TI - [Not Available]. PMID- 20296957 TI - [Not Available]. PMID- 20296958 TI - [Not Available]. PMID- 20296959 TI - [Not Available]. PMID- 20296960 TI - [Not Available]. PMID- 20296961 TI - [Not Available]. PMID- 20296963 TI - [Not Available]. PMID- 20296962 TI - [Not Available]. PMID- 20296964 TI - [Not Available]. PMID- 20296965 TI - [Not Available]. PMID- 20296966 TI - [Not Available]. PMID- 20296967 TI - [Not Available]. PMID- 20296968 TI - [Not Available]. PMID- 20296969 TI - [Not Available]. PMID- 20296970 TI - [Not Available]. PMID- 20296972 TI - [Not Available]. PMID- 20296973 TI - [Not Available]. PMID- 20296971 TI - [Not Available]. PMID- 20296974 TI - [Not Available]. PMID- 20296975 TI - [Not Available]. PMID- 20296976 TI - [Not Available]. PMID- 20296977 TI - [Not Available]. PMID- 20296978 TI - [Not Available]. PMID- 20296979 TI - [Not Available]. PMID- 20296980 TI - [Not Available]. PMID- 20296981 TI - [Not Available]. PMID- 20296982 TI - [Not Available]. PMID- 20296983 TI - [Not Available]. PMID- 20296984 TI - [Not Available]. PMID- 20296985 TI - [Not Available]. PMID- 20296986 TI - [Not Available]. PMID- 20296988 TI - [Not Available]. PMID- 20296987 TI - [Not Available]. PMID- 20296989 TI - [Not Available]. PMID- 20296990 TI - [Not Available]. PMID- 20296991 TI - [Not Available]. PMID- 20296992 TI - [Not Available]. PMID- 20296993 TI - [Not Available]. PMID- 20296994 TI - [Not Available]. PMID- 20296996 TI - [Not Available]. PMID- 20296995 TI - [Not Available]. PMID- 20296997 TI - The etiology of arteriosclerosis. PMID- 20296998 TI - Curare. PMID- 20296999 TI - A history of the plague. PMID- 20297000 TI - Diabetes mellitus. PMID- 20297001 TI - The aetiology and diagnosis of diabetes mellitus. PMID- 20297002 TI - The diabetic maternity patient and her baby. PMID- 20297003 TI - A review of some of the past and present types of psychiatric therapy. PMID- 20297004 TI - Obscure hematemesis; gastroscopy, an aid in its diagnosis. PMID- 20297005 TI - Acanthosis nigricans; a case of the benign type in an eight-year old girl. PMID- 20297006 TI - Today's challenge. PMID- 20297007 TI - Electrocardiographic changes occurring during antimony therapy. PMID- 20297008 TI - Primary cancer of the lung. PMID- 20297009 TI - Office gynecology. PMID- 20297010 TI - Mortality from coronary disease by sex, age, and race. PMID- 20297011 TI - Repair of posterior wall vaginal hernia from below, without opening the sac; report of case. PMID- 20297012 TI - [Not Available]. PMID- 20297013 TI - [Not Available]. PMID- 20297014 TI - [Not Available]. PMID- 20297015 TI - [Not Available]. PMID- 20297016 TI - [Not Available]. PMID- 20297017 TI - [Not Available]. PMID- 20297018 TI - [Not Available]. PMID- 20297019 TI - [Not Available]. PMID- 20297020 TI - [Not Available]. PMID- 20297021 TI - [Not Available]. PMID- 20297022 TI - [Not Available]. PMID- 20297023 TI - [Not Available]. PMID- 20297024 TI - [Not Available]. PMID- 20297025 TI - [Not Available]. PMID- 20297026 TI - [Not Available]. PMID- 20297027 TI - [Not Available]. PMID- 20297029 TI - [Not Available]. PMID- 20297028 TI - [Not Available]. PMID- 20297031 TI - [Not Available]. PMID- 20297030 TI - [Not Available]. PMID- 20297032 TI - [Not Available]. PMID- 20297033 TI - [Not Available]. PMID- 20297034 TI - Duplication of chromosome parts as a factor in evolution. PMID- 20297035 TI - The genetic aspects of natural populations; actual and potential gene flow in natural populations. PMID- 20297036 TI - Heredity of geographically and ecologically isolated races. PMID- 20297037 TI - The mating-anatomy technique as applied to polygyrid landsnails. PMID- 20297038 TI - Inversion gradients and selection in ecological races of Drosophila funebris. PMID- 20297039 TI - Stability of family names; some principles and problems. PMID- 20297040 TI - [Not Available]. PMID- 20297041 TI - [Not Available]. PMID- 20297042 TI - [Not Available]. PMID- 20297043 TI - The comparative physiology of respiratory organs. PMID- 20297044 TI - [Not Available]. PMID- 20297045 TI - [Not Available]. PMID- 20297046 TI - [Not Available]. PMID- 20297047 TI - [Not Available]. PMID- 20297048 TI - [Not Available]. PMID- 20297049 TI - [Not Available]. PMID- 20297050 TI - [Not Available]. PMID- 20297051 TI - [Not Available]. PMID- 20297052 TI - [Not Available]. PMID- 20297053 TI - [Not Available]. PMID- 20297054 TI - [Not Available]. PMID- 20297055 TI - [Not Available]. PMID- 20297056 TI - [Not Available]. PMID- 20297057 TI - [Not Available]. PMID- 20297058 TI - [Not Available]. PMID- 20297059 TI - [Not Available]. PMID- 20297060 TI - Unit dimensions and space group of TI2Cl3. PMID- 20297061 TI - [Not Available]. PMID- 20297062 TI - [Not Available]. PMID- 20297064 TI - Urine therapy. PMID- 20297063 TI - Microincineration of sea urchin eggs during cleavage. PMID- 20297065 TI - [Not Available]. PMID- 20297066 TI - [Not Available]. PMID- 20297067 TI - Concentration of isotopes of potassium by the counter-current electromigration method. PMID- 20297068 TI - Concentration of potassium by countercurrent electromigration; some theoretical aspects of the operation. PMID- 20297069 TI - Concentration of isotopes of chlorine by the countercurrent electromigration method. PMID- 20297070 TI - Surface tensions of some optical glasses. PMID- 20297071 TI - The late-glacial period. PMID- 20297072 TI - Science in adult education. PMID- 20297073 TI - Electron microscopy of tobacco necrosis virus crystals. PMID- 20297074 TI - The renal factor in alloxan diabetes. PMID- 20297075 TI - Practical three-hour and two-hour cylinder-plate assays for penicillin. PMID- 20297076 TI - Nucleotide metabolism of bacteria and the bacterial nucleus. PMID- 20297077 TI - Cytochemical effects of oestradiol. PMID- 20297078 TI - Origin of erythrocytes. PMID- 20297079 TI - What is emotion? PMID- 20297080 TI - Bactericidal effect of the war-time penny. PMID- 20297081 TI - A systematic study of the main arteries in the region of the heart; Aves V, Sphenisciformes. PMID- 20297082 TI - Some algae, including new species, from New Mexico. PMID- 20297083 TI - Memorial Laboratory, National Institute of Health. PMID- 20297084 TI - The numbers and distribution of mankind. PMID- 20297085 TI - The Senate ponders social science. PMID- 20297086 TI - The university presses; their function. PMID- 20297087 TI - The university presses and the popularization of science. PMID- 20297088 TI - Obsolete library books. PMID- 20297090 TI - Application of the electronic theory to some simple organic reactions. PMID- 20297089 TI - The number of exceptional children in Kansas. PMID- 20297091 TI - Comparison of the scores of design engineering personnel with factory workers on the MacQuarrie mechanical performance ability tests. PMID- 20297092 TI - A brief history of the American Philosophical Society. PMID- 20297093 TI - Studies on the specificity and sensitivity of certain colorimetric reactions of the amino acids. PMID- 20297094 TI - Differentiation of motor and sensory neurons in chick embryos after the substitution of growing tumor masses for the hind limb periphery. PMID- 20297095 TI - Clinical experience with hemoglobin-saline solutions. PMID- 20297096 TI - The quantitative effects of narcotics and allied inhibitors on isolated enzyme systems. PMID- 20297097 TI - Investigation on respiration in the colorless flagellate, Chilomonas paramecium, with special emphasis on the vitamins involved in the respiratory mechanism. PMID- 20297098 TI - Dreamy states, epileptic aura, depersonalisation and psychasthenic fits; a few comments and reflections. PMID- 20297099 TI - A case of matricide the perpetrator of which subsequently proved to be a schizophreniac. PMID- 20297100 TI - On the treatment of tabes dorsalis with artificial fever (hyperthermia treatment). PMID- 20297101 TI - A case of delirium acutum after erysipelas treated with sulfonamide associated with hypothalamic and pituitary alterations; with some comments on the pathology of acute exogenous psychoses. PMID- 20297102 TI - On the psychopathology of disseminated sclerosis. PMID- 20297104 TI - The care of the feeble-minded. PMID- 20297103 TI - Technical tricks in the examination of neurotics. PMID- 20297105 TI - A psychological treatise on Hans Andersen's fairy tale, Thumbelina. PMID- 20297106 TI - Action potentials in pathological postural reflex activity (spasticity and rigidity). PMID- 20297107 TI - Case of double athetosis with status marmoratus. PMID- 20297108 TI - Theft with atypical motive. PMID- 20297109 TI - The contribution of psychiatry to social life. PMID- 20297110 TI - On female criminality during the climacteric. PMID- 20297111 TI - A family with Alzheimer's disease. PMID- 20297112 TI - Pituitary dwarfism. PMID- 20297113 TI - Criminal frequency in a Danish rural area. PMID- 20297114 TI - Early differential diagnosis between psychogenic psychosis and schizophrenia. PMID- 20297115 TI - Danish doctorate theses on psychiatry and neurology (1835-1945). PMID- 20297116 TI - A few comments on the position of psychotherapy in Denmark in connection with a case of anxiety neurosis cured by means of hypnosis. PMID- 20297117 TI - Dynamite encephalosis. PMID- 20297118 TI - On delirium acutum, with special reference to biochemical changes. PMID- 20297119 TI - The morphology of handwriting in congenital word-blindness. PMID- 20297120 TI - Complications and dangers in the use of hypnotism, a brief survey. PMID- 20297121 TI - Criminality and pathology. PMID- 20297122 TI - On the hydrochloric acid-collargol reaction in the spinal fluid. PMID- 20297123 TI - A pair of book-plates. PMID- 20297124 TI - Some preliminary remarks concerning the concept of personality types. PMID- 20297125 TI - Induced abortion on eugenic indications. PMID- 20297126 TI - Punishment or impunity? PMID- 20297127 TI - [Not Available]. PMID- 20297128 TI - Psychiatric observations and experiences during the German occupation of Norway. PMID- 20297129 TI - Encephalopathia allergica e neosalvarsano; a survey with a case. PMID- 20297131 TI - On the question of psychologically conditioned features in the Korsakow syndroma (clinical and experimental studies of a Korsakow case, extended over several years). PMID- 20297132 TI - [Not Available]. PMID- 20297130 TI - Vasomotor Jacksonian epilepsy. PMID- 20297133 TI - [Not Available]. PMID- 20297134 TI - [Not Available]. PMID- 20297135 TI - On inhibited and over-excited deep reflexes in neurotic patients. PMID- 20297136 TI - Contribution to the history of dementia paralytica with special reference to to the contributions of Scandinavian, particularly Danish scientists. PMID- 20297137 TI - A case of Gerstmann's syndrome. PMID- 20297138 TI - [Not Available]. PMID- 20297139 TI - Admissions to the mental hospital at Nykobing Sjalland caused by the events in Denmark in connection with the surrender of the German occupation forces. PMID- 20297140 TI - [Not Available]. PMID- 20297142 TI - Congenital speech disorders. PMID- 20297141 TI - Psychopathic personality traits; terminological considerations. PMID- 20297143 TI - On the discharge of psychiatric patients after hospitalization for years. PMID- 20297144 TI - On certain mathematical problems connected with the determination of anthropometrical and diagnostical indices. PMID- 20297145 TI - Mental sequelae to suicidal attempts by hanging. PMID- 20297146 TI - A psychiatric establishment for investigation, training and treatment of psychologically abnormal criminals. PMID- 20297147 TI - Amyotrophic cerebrospinal syphilis. PMID- 20297148 TI - On the applicability of serologic reactions in the psychiatric clinic. PMID- 20297149 TI - Human heredity and mental deficiency. PMID- 20297150 TI - Sterilization of the mentally deficient under state laws. PMID- 20297151 TI - Ten years research in mental deficiency; a study based on 200 autopsies. PMID- 20297152 TI - Skin eruption due to phenobarbital among mentally defective epileptic patients. PMID- 20297153 TI - Treatment of epilepsy with tridione. PMID- 20297154 TI - Psychological variation within a homogeneous psychometric group. PMID- 20297155 TI - The use of multi-sensory aids in guiding the slow-learning pupil in the understanding of arithmetic. PMID- 20297156 TI - Early prognosis in mental defects. PMID- 20297157 TI - Personality in mongolism with special reference to the incidence of catatonic psychosis. PMID- 20297158 TI - The incident of maladjustment among mental defectives in military environment. PMID- 20297159 TI - Psychoneuroses in the mentally retarded. PMID- 20297161 TI - The education of the institutionalized mental defective by means of a social program. PMID- 20297160 TI - Training program for middle grade children at the Southbury Training School. PMID- 20297162 TI - The Wayne County Training School program; the general educational plan. PMID- 20297163 TI - The education program in the Rome State School. PMID- 20297165 TI - Occupational therapy; its contribution to the training of mentally deficient patients at the Newark State School. PMID- 20297164 TI - Methods and techniques used in occupational therapy treatment for the imbecile. PMID- 20297166 TI - Recreation for the patients in the institutions for mental defectives. PMID- 20297167 TI - Botleys Park Mental Deficiency Colony, Chertsey, Surrey, England, during the war, 1939-1945. PMID- 20297169 TI - The Haven, colony houses. PMID- 20297168 TI - The Lapeer program. PMID- 20297170 TI - Analysis of the results of the Rome State School training program. PMID- 20297171 TI - Basic anxiety. PMID- 20297172 TI - The traumatic syndrome. PMID- 20297173 TI - Psychiatry and applied anthropology in psychological warfare against Japan. PMID- 20297174 TI - Psychoanalysis and education. PMID- 20297175 TI - Neurotic conflict and physical symptoms. PMID- 20297176 TI - Psychoanalysis and the news world. PMID- 20297177 TI - The Association, past, present, and future. PMID- 20297178 TI - Psychoanalysis and politics. PMID- 20297179 TI - The role of psychoanalysis in the community. PMID- 20297180 TI - The future of psychoanalysis. PMID- 20297181 TI - Cerebral anoxia from high altitude asphyxiation; a clinicopathologic study of two fatal cases with unusually long survival and a clinical report of a nonfatal case. PMID- 20297182 TI - Cerebellar medulloblastoma in adults. PMID- 20297183 TI - Static tremor with hemiplegia; report of a case; development, progression for seven years and postmortem histologic observations. PMID- 20297184 TI - Japanese B encephalitis; clinical observations in an outbreak on Okinawa Shima. PMID- 20297185 TI - Incidence of anisocoria and difference in size of palpebral fissures in five hundred normal subjects. PMID- 20297186 TI - Relation of mental imagery to hallucinations. PMID- 20297187 TI - Medulloblastoma of the cerebellum, with survival for 17 years. PMID- 20297188 TI - Bilateral and multiple ruptured disk as a cause of persistent symptoms following operation for herniated disk. PMID- 20297189 TI - Electroshock and personality structure. PMID- 20297190 TI - Elements in psychotherapy. PMID- 20297191 TI - Results of hospital treatment, including electric shock, of psychoneurotic patients. PMID- 20297192 TI - The problem of alcoholism. PMID- 20297193 TI - The conditioned reflex treatment of alcoholism. PMID- 20297194 TI - Alcoholics Anonymous. PMID- 20297196 TI - [Not Available]. PMID- 20297195 TI - [Not Available]. PMID- 20297197 TI - [Not Available]. PMID- 20297198 TI - Genetical causes of schizophrenic symptoms. PMID- 20297199 TI - [Not Available]. PMID- 20297200 TI - [Not Available]. PMID- 20297201 TI - [Not Available]. PMID- 20297202 TI - [Not Available]. PMID- 20297203 TI - [Not Available]. PMID- 20297204 TI - [Not Available]. PMID- 20297205 TI - [Not Available]. PMID- 20297206 TI - [Not Available]. PMID- 20297207 TI - [Not Available]. PMID- 20297208 TI - [Not Available]. PMID- 20297209 TI - [Not Available]. PMID- 20297210 TI - [Not Available]. PMID- 20297211 TI - [Not Available]. PMID- 20297212 TI - [Not Available]. PMID- 20297213 TI - [Not Available]. PMID- 20297214 TI - [Not Available]. PMID- 20297215 TI - [Not Available]. PMID- 20297216 TI - [Not Available]. PMID- 20297217 TI - [Not Available]. PMID- 20297218 TI - [Not Available]. PMID- 20297219 TI - [Not Available]. PMID- 20297220 TI - [Not Available]. PMID- 20297221 TI - [Not Available]. PMID- 20297222 TI - [Not Available]. PMID- 20297223 TI - [Not Available]. PMID- 20297224 TI - [Not Available]. PMID- 20297225 TI - [Not Available]. PMID- 20297226 TI - A suggested definition of intelligence. PMID- 20297227 TI - Mental health approach to juvenile delinquency. PMID- 20297228 TI - Measles. PMID- 20297229 TI - Tetralogy of Fallot. PMID- 20297230 TI - Nursing care of a child with tetralogy of Fallot. PMID- 20297231 TI - A clean procedure for formula preparation. PMID- 20297232 TI - What's wrong with this picture? [private duty nursing in hospitals]. PMID- 20297233 TI - Measuring and recording oral fluid intake. PMID- 20297234 TI - FOOT CARE for you and your patient. PMID- 20297235 TI - Foot supports in polio. PMID- 20297236 TI - Shorter and sharper testing tools for the pre-nursing and guidance test service. PMID- 20297237 TI - REQUIREMENTS for admission to schools of nursing. PMID- 20297238 TI - What is a consultant? with special reference to the venereal disease field. PMID- 20297239 TI - The public health nurse in communicable disease control. PMID- 20297240 TI - Treatment progress in venereal disease control. PMID- 20297241 TI - The nurse in a changing venereal disease program. PMID- 20297243 TI - M. S. Hygiene, Alaska's floating health unit. PMID- 20297242 TI - Community planning for parent education. PMID- 20297244 TI - Physical therapy aspects of cerebral palsy. PMID- 20297245 TI - Further data on glare ratings. PMID- 20297246 TI - Brightness distribution in rooms. PMID- 20297247 TI - The measurement of fluorescent lamps and luminaires. PMID- 20297248 TI - The characteristics and application of flashtubes. PMID- 20297249 TI - New developments in mercury lamps and their applications. PMID- 20297250 TI - Quality lighting in schools. PMID- 20297251 TI - Classroom fields of vision. PMID- 20297253 TI - [Not Available]. PMID- 20297252 TI - Tropical nutritional amblyopia ("camp eyes"). PMID- 20297254 TI - [Not Available]. PMID- 20297255 TI - [Not Available]. PMID- 20297256 TI - On the distribution of glutathione and vitamin C in the lens and cornea. PMID- 20297257 TI - [Not Available]. PMID- 20297258 TI - [Not Available]. PMID- 20297260 TI - Descemet-rupture and birth-trauma. PMID- 20297259 TI - [Not Available]. PMID- 20297261 TI - Arachnodactylia and diencephalon. PMID- 20297262 TI - Cataract and carbo-hydrate metabolism of the lens. PMID- 20297263 TI - Acuity of vision in connection with the distribution of the percipient elements over the retina. PMID- 20297264 TI - A perimeter-scheme depicting equivalently. PMID- 20297265 TI - Computation on seeing dimly. PMID- 20297266 TI - Treatment of macular degeneration. PMID- 20297267 TI - Chronic inflammation of the glands of Meibom. PMID- 20297268 TI - Some remarks about injuries to the eye. PMID- 20297269 TI - Mercuriosis of the lens. PMID- 20297270 TI - Glaucoma; vascular necrosis; expulsive haemorrhage. PMID- 20297271 TI - Xanthelasmata and vegetative neurosis. PMID- 20297272 TI - Communication about three cases of post-operative purulent infection of the vitreous body, cured by injecting penicilline into the anterior ocular chamber and vitreous body. PMID- 20297273 TI - A case of petrifying conjunctivitis (Leber) caused by a mould. PMID- 20297274 TI - Acrylic ocular prosthesis; a new method. PMID- 20297275 TI - Notes on the aetiology of horizontal imbalance. PMID- 20297276 TI - Centenary of Babbage's ophthalmoscope. PMID- 20297277 TI - Personality problems in the guide dog relation. PMID- 20297278 TI - A new technique for the insertion of a columellar strut. PMID- 20297279 TI - A precise method of approximating the mesial crura. PMID- 20297280 TI - Ocular torsion in health and disease. PMID- 20297281 TI - Regional injection of penicillin in phlegmons of the nose and throat. PMID- 20297283 TI - The effect of visual training on existing myopia. PMID- 20297282 TI - Vitreous transplantation. PMID- 20297284 TI - Nonperforating ocular injuries in soldiers. PMID- 20297285 TI - New forceps for the removal of nonmagnetic foreign bodies from the vitreous. PMID- 20297286 TI - A method for visualizing the anterior segment of the globe by stereoscopic roentgenography. PMID- 20297287 TI - A new prism holder. PMID- 20297288 TI - A new ophthalmoscope demonstration. PMID- 20297289 TI - An illuminated retractor speculum. PMID- 20297290 TI - Two accommodating rules of opaque plastic. PMID- 20297291 TI - The Luckiesh-Berens tangent screen illuminator. PMID- 20297292 TI - Compensating convergence and accommodation device. PMID- 20297293 TI - Septic thrombophlebitis of the neck. PMID- 20297294 TI - Otolaryngological aspects of wry neck. PMID- 20297295 TI - Deafness of psychic origin and its response to narcosynthesis. PMID- 20297296 TI - The fitting of hearing aids. PMID- 20297297 TI - Methods for recording audiometric findings recommended by the Committee on the Conservation of Hearing. PMID- 20297298 TI - Lipreading demonstration. PMID- 20297299 TI - The measurement of hearing. PMID- 20297300 TI - The measurement of hearing. PMID- 20297301 TI - Hyperplastic callus simulating sarcoma in two cases of fragilitas ossium. PMID- 20297302 TI - Calcification of the lung alveoli. PMID- 20297303 TI - A paraganglion related to the ductus arteriosus. PMID- 20297304 TI - Pigmentary changes in familial non-haemolytic jaundice. PMID- 20297305 TI - Gliomata of the nose and oral cavity; a report of two cases. PMID- 20297306 TI - Cerebral arteritis and phlebitis in pneumococcal meningitis. PMID- 20297307 TI - Basophilism and carcinoma of the pancreas. PMID- 20297308 TI - Amyoplasia congenita. PMID- 20297309 TI - Primary pulmonary hypertension. PMID- 20297310 TI - Salivary adenoma and adenolymphoma. PMID- 20297311 TI - Haemolytic icterus (acholuric jaundice) congenital and acquired. PMID- 20297312 TI - Observations on the pulmonary macrophage system. PMID- 20297313 TI - Myocarditis in Friedreich's ataxia. PMID- 20297314 TI - The blood picture and plasma level following injury. PMID- 20297315 TI - The changes in the kidneys in carbon tetrachloride poisoning, and their resemblance to those in the crush syndrome. PMID- 20297316 TI - [Not Available]. PMID- 20297317 TI - [Not Available]. PMID- 20297318 TI - [Not Available]. PMID- 20297319 TI - [Not Available]. PMID- 20297320 TI - [Not Available]. PMID- 20297321 TI - [Not Available]. PMID- 20297322 TI - [Not Available]. PMID- 20297323 TI - [Not Available]. PMID- 20297324 TI - [Not Available]. PMID- 20297325 TI - [Not Available]. PMID- 20297326 TI - [Not Available]. PMID- 20297327 TI - [Not Available]. PMID- 20297328 TI - [Not Available]. PMID- 20297329 TI - [Not Available]. PMID- 20297330 TI - [Not Available]. PMID- 20297331 TI - [Not Available]. PMID- 20297332 TI - [Not Available]. PMID- 20297333 TI - [Not Available]. PMID- 20297334 TI - [Not Available]. PMID- 20297335 TI - [Not Available]. PMID- 20297336 TI - [Not Available]. PMID- 20297337 TI - [Not Available]. PMID- 20297338 TI - [Not Available]. PMID- 20297339 TI - [Not Available]. PMID- 20297340 TI - [Not Available]. PMID- 20297342 TI - [Not Available]. PMID- 20297341 TI - [Not Available]. PMID- 20297343 TI - [Not Available]. PMID- 20297344 TI - [Not Available]. PMID- 20297345 TI - [Not Available]. PMID- 20297346 TI - [Not Available]. PMID- 20297347 TI - [Not Available]. PMID- 20297348 TI - [Not Available]. PMID- 20297349 TI - [Not Available]. PMID- 20297350 TI - [Not Available]. PMID- 20297351 TI - [Not Available]. PMID- 20297352 TI - [Not Available]. PMID- 20297353 TI - [Not Available]. PMID- 20297354 TI - [Not Available]. PMID- 20297355 TI - [Not Available]. PMID- 20297357 TI - A case of toxoplamosis; with recovery. PMID- 20297356 TI - [Not Available]. PMID- 20297358 TI - [Not Available]. PMID- 20297359 TI - A case of D-vitamin intoxication. PMID- 20297360 TI - [Not Available]. PMID- 20297361 TI - [Not Available]. PMID- 20297362 TI - [Not Available]. PMID- 20297363 TI - [Not Available]. PMID- 20297364 TI - [Not Available]. PMID- 20297365 TI - [Not Available]. PMID- 20297366 TI - [Not Available]. PMID- 20297367 TI - [Not Available]. PMID- 20297368 TI - [Not Available]. PMID- 20297369 TI - [Not Available]. PMID- 20297370 TI - [Not Available]. PMID- 20297371 TI - [Not Available]. PMID- 20297372 TI - [Not Available]. PMID- 20297373 TI - [Not Available]. PMID- 20297374 TI - Height and weight in relation to onset of puberty in boys. PMID- 20297375 TI - Some observations on the growth of children. PMID- 20297376 TI - The blood in infancy. PMID- 20297377 TI - Biliary obstruction associated with icterus gravis neonatorum. PMID- 20297378 TI - The etiology of intermittent oesophageal regurgitation and haematemesis in infants. PMID- 20297379 TI - Observations on haemolytic disease of the newborn. PMID- 20297380 TI - The treatment of erythroblastosis foetalis. PMID- 20297381 TI - The plasma volume in nephritis. PMID- 20297382 TI - The convalescent care of rheumatic fever patients. PMID- 20297383 TI - Allergy in childhood; the long range view. PMID- 20297384 TI - Incontinence of urine in children. PMID- 20297385 TI - Pertussis encephalopathy. PMID- 20297386 TI - Tuberculous meningitis. PMID- 20297387 TI - [Not Available]. PMID- 20297388 TI - [Not Available]. PMID- 20297389 TI - [Not Available]. PMID- 20297390 TI - [Not Available]. PMID- 20297391 TI - [Not Available]. PMID- 20297392 TI - [Not Available]. PMID- 20297393 TI - [Not Available]. PMID- 20297394 TI - [Generalized bone disease in childhood]. PMID- 20297395 TI - [Not Available]. PMID- 20297396 TI - [Not Available]. PMID- 20297397 TI - [Not Available]. PMID- 20297398 TI - [Not Available]. PMID- 20297399 TI - [Not Available]. PMID- 20297400 TI - [Not Available]. PMID- 20297401 TI - [Not Available]. PMID- 20297402 TI - [Not Available]. PMID- 20297403 TI - [Not Available]. PMID- 20297404 TI - [Not Available]. PMID- 20297405 TI - [Not Available]. PMID- 20297406 TI - The approach to child guidance in Victoria. PMID- 20297407 TI - Deficits in diarrhea. PMID- 20297408 TI - Rickettsial diseases of childhood; a clinical pathologic study of tick typhus, Rocky Mountain spotted fever and murine typhus, endemic typhus. PMID- 20297409 TI - Early evidence of psychoses in children; with special reference to schizophrenia. PMID- 20297410 TI - Streptomycin; a review. PMID- 20297412 TI - Celiac syndrome; the relationship of celiac disease, starch intolerance, and steatorrhea. PMID- 20297411 TI - Osseous congenital syphilis; effects of penicillin on rate of healing. PMID- 20297413 TI - An evaluation of benadryl, pyribenzamine, and other so-called antihistaminic drugs in the treatment of allergy. PMID- 20297414 TI - Genitourinary conditions in infants and children. PMID- 20297415 TI - Research report of child health needs and interests on which to revise health instruction in Denver schools. PMID- 20297416 TI - The American School Health Association in retrospect and in prospect. PMID- 20297417 TI - The teachers' role in early recognition of the maladjusted child. PMID- 20297418 TI - New York State training program for dental hygienists. PMID- 20297419 TI - Results of fifteen years of tuberculosis control in rural Minnesota. PMID- 20297420 TI - Orthoptic treatment, a beneficial procedure when properly used. PMID- 20297421 TI - The nuisance diseases. PMID- 20297422 TI - Dental health for children and youth. PMID- 20297423 TI - Diisopropyl fluorophosphate. PMID- 20297425 TI - Preparation and clinical uses of protein hydrolysates. PMID- 20297424 TI - Recent advances in therapeutic agents. PMID- 20297426 TI - Mascara; a simply prepared cosmetic. PMID- 20297427 TI - Application to medicinal chemicals of a new notation for organic compounds. PMID- 20297428 TI - Cochineal. PMID- 20297429 TI - Pharmacy in Colonial North America. PMID- 20297430 TI - Sinusitis; its problems and complications. PMID- 20297431 TI - ENDOCRINE glands in health and disease. PMID- 20297432 TI - The treatment of some common skin diseases. PMID- 20297433 TI - Trace metals and chemotherapy. PMID- 20297435 TI - A survey of diagnostic agents. PMID- 20297434 TI - The stabilisation and drying of digitialis leaves. PMID- 20297436 TI - Urea-resin-treated paper. PMID- 20297437 TI - [Not Available]. PMID- 20297438 TI - [Not Available]. PMID- 20297439 TI - [Not Available]. PMID- 20297440 TI - [Not Available]. PMID- 20297441 TI - Maternity and child welfare in a large British city. PMID- 20297442 TI - Regulation of housing; hints for health officers. PMID- 20297443 TI - Ideal intake of calories and specific nutrients. PMID- 20297444 TI - Effect of restricted feeding upon aging and chronic diseases in rats and dogs. PMID- 20297445 TI - Effect of ultra-violet irradiation of classrooms on spread of measels in large rural central schools. PMID- 20297446 TI - Use of census tracts in the analysis of city health problems. PMID- 20297447 TI - The correlation of laboratory and clinical evidence of virulence of C. diphtheriae. PMID- 20297449 TI - WATER supply. PMID- 20297448 TI - Present recommendations concerning treatment and prophylaxis of diphtheria. PMID- 20297451 TI - Prevention of disease in the USSR. PMID- 20297450 TI - An epidemic of an acute meningo-encephalitis in Giles County, Tennessee; an unusual disease. PMID- 20297452 TI - The challenge of psychiatry in 1947. PMID- 20297454 TI - Nutrition and school children. PMID- 20297453 TI - Rates of stillbirths in Canada. PMID- 20297455 TI - Ornithosis among wild pigeons in Ontario. PMID- 20297456 TI - Inspection of funeral homes. PMID- 20297457 TI - [The population and population dynamics of Austria in 1945/46]. PMID- 20297458 TI - [First occurrence of the word 'statistics' in Hungary, and the beginning of the science of statistics in Hungary]. PMID- 20297459 TI - The Lancashire mass radiography unit. PMID- 20297460 TI - The use of D. D. T. for Pediculus capitis infestation in school children. PMID- 20297461 TI - The Curtis report. PMID- 20297462 TI - Low incidence of Enterobius vermicularis in natives of Guam, M. I. PMID- 20297463 TI - Intradermal reactions to fresh and stored antigens prepared from cercariae of Schistosoma mansoni. PMID- 20297464 TI - The relation of brucellosis to human welfare. PMID- 20297465 TI - The Ponce malaria control project. PMID- 20297467 TI - [Not Available]. PMID- 20297466 TI - Schistosomiasis mansoni in the Republic of Santo Domingo; with a report of six cases studied. PMID- 20297468 TI - [Not Available]. PMID- 20297469 TI - [Not Available]. PMID- 20297470 TI - [Not Available]. PMID- 20297471 TI - Evaluation of methods of heating sludge. PMID- 20297472 TI - Phosphates in sewage and sludge treatment; effect on coagulation, clarification and sludge volume. PMID- 20297473 TI - Concentration of activated sludge. PMID- 20297474 TI - Sanitary sewers; how big should they be? some evidence indicating that money is being wasted in over-design of lateral sewers. PMID- 20297475 TI - Developments of 1946 in sewage and industrial waste treatment; a critical review. PMID- 20297476 TI - [Not Available]. PMID- 20297477 TI - [Not Available]. PMID- 20297478 TI - [Not Available]. PMID- 20297479 TI - [Not Available]. PMID- 20297480 TI - [Not Available]. PMID- 20297481 TI - [Not Available]. PMID- 20297482 TI - [Not Available]. PMID- 20297483 TI - [Not Available]. PMID- 20297484 TI - Treatment of oesophageal varices by injections of sclerosing agents through oesophagoscope in splenectomized patient suffering from splenic phlebostenosis (splenic anemia); a case with autopsy. PMID- 20297485 TI - Prevention of evacuation difficulties of the stomach after partial gastrectomy. PMID- 20297486 TI - Intraarticular fractures in the upper end of the tibia and lower end of the femur. PMID- 20297487 TI - [Not Available]. PMID- 20297488 TI - Headache after spinal anesthesia and a technique for lessening its frequency. PMID- 20297489 TI - On dislocation and fracture-dislocation of the spinal column. PMID- 20297490 TI - Four cases of tuberculosis of the kidney. PMID- 20297491 TI - Accidents in childhood. PMID- 20297492 TI - Peripheral injuries to the spinal accessory nerve. PMID- 20297493 TI - Malignant goiter. PMID- 20297495 TI - On conservative surgery in hydronephrosis. PMID- 20297494 TI - [Not Available]. PMID- 20297496 TI - [Not Available]. PMID- 20297497 TI - [Not Available]. PMID- 20297498 TI - [Not Available]. PMID- 20297499 TI - [Not Available]. PMID- 20297500 TI - [Not Available]. PMID- 20297501 TI - [Not Available]. PMID- 20297502 TI - [Not Available]. PMID- 20297503 TI - [Not Available]. PMID- 20297504 TI - [Not Available]. PMID- 20297506 TI - [Not Available]. PMID- 20297505 TI - [Not Available]. PMID- 20297507 TI - [Not Available]. PMID- 20297508 TI - [Not Available]. PMID- 20297509 TI - [Not Available]. PMID- 20297510 TI - [Not Available]. PMID- 20297511 TI - [Not Available]. PMID- 20297512 TI - [Not Available]. PMID- 20297513 TI - [Not Available]. PMID- 20297514 TI - [Not Available]. PMID- 20297515 TI - [Not Available]. PMID- 20297516 TI - [Not Available]. PMID- 20297517 TI - [Not Available]. PMID- 20297518 TI - [Not Available]. PMID- 20297519 TI - [Not Available]. PMID- 20297520 TI - [Not Available]. PMID- 20297521 TI - [Not Available]. PMID- 20297522 TI - The surgical treatment of decubitus ulcers. PMID- 20297523 TI - Principles of plastic surgery. PMID- 20297524 TI - [Not Available]. PMID- 20297525 TI - [Not Available]. PMID- 20297526 TI - [Not Available]. PMID- 20297527 TI - [Not Available]. PMID- 20297528 TI - [Not Available]. PMID- 20297529 TI - [Not Available]. PMID- 20297530 TI - [Not Available]. PMID- 20297531 TI - [Not Available]. PMID- 20297532 TI - Streptomycin. PMID- 20297533 TI - The examination of contacts. PMID- 20297534 TI - [Not Available]. PMID- 20297535 TI - [Not Available]. PMID- 20297536 TI - [Not Available]. PMID- 20297537 TI - [Not Available]. PMID- 20297538 TI - [Not Available]. PMID- 20297539 TI - [Not Available]. PMID- 20297540 TI - Newcastle disease in England and Wales. PMID- 20297541 TI - Tick-borne fever in young lambs. PMID- 20297542 TI - Some aspects of immunity to tick-borne fever in hogs. PMID- 20297543 TI - Infectious catarrhal fever of dogs. PMID- 20297544 TI - Running fits in dogs. PMID- 20297545 TI - [The sons of dissidence: the sin of sodomy and its infamous records]. PMID- 20297546 TI - [From the kingdom to Rio: New Christians, migration, social mobility, and sociability in Rio de Janeiro]. PMID- 20297547 TI - Education and training in anaesthesia and intensive care--contemporary considerations. PMID- 20297548 TI - [Identity crisis as a migration-causing factor in the post-Soviet period]. PMID- 20297549 TI - Scientists at sea: British seagoing naturalists in Australian waters in the nineteenth century. PMID- 20297550 TI - Dr. Alan Duncan--Chief Editor of Anaesthesia and Intensive Care: 2003 to 2009. PMID- 20297551 TI - [Breves nocoes sobre a Medicina Cafreal do Districto de Sofala: Portuguese knowledge of medicinal herbs and plants on the southeast coast of Africa in the second half of the 19th century]. PMID- 20297552 TI - Vale the index. PMID- 20297553 TI - Progress at the journal. PMID- 20297554 TI - Case reports or correspondence? PMID- 20297555 TI - [Abstracts from the 27th International Congress of the Association of French speaking Dermatologists, 11-14 February 2009, Alger, Algeria]. PMID- 20297556 TI - [Iron chelation significantly improves the median disease free survival in iron overload]. PMID- 20297557 TI - On disruptive innovations in prosthodontics- can we hide our operatory? PMID- 20297558 TI - State wellness initiatives. PMID- 20297559 TI - ["I'm well aware of the problems and crisis in psychiatry . . . " Interview with Dr. Janos Harmatta by Gyongyi B.Kiraly]. PMID- 20297560 TI - [Role of biological statistics in clinical studies]. PMID- 20297561 TI - How health reform legislation will affect Medicare beneficiaries. AB - Despite criticism that health reform legislation will result in cuts to Medicare, the bills passed by the House of Representatives and the Senate, as well as President Obama's proposal, contain provisions that would strengthen the program by reducing costs for prescription drugs, expanding coverage for preventive care, providing more help for low-income beneficiaries, and supporting accessible, coordinated, and comprehensive care that effectively responds to patients' needs. The legislation also would help to extend the program's fiscal solvency--for nine years, under the Senate bill. This issue brief examines the provisions in the pending legislation and how each one would work to improve benefits, extend the fiscal solvency of the Medicare Hospital Insurance Trust Fund, reduce pressure on the federal budget, and contribute to moving the health care system toward better access to care, improved quality, and greater efficiency. PMID- 20297562 TI - [A non smoking operation]. PMID- 20297563 TI - [To dictate and to write at the same time--that is the answer]. PMID- 20297564 TI - [Miscarriage or not miscarriage--correct diagnosis not always easy. Early ultrasound can give several uncertain diagnoses]. PMID- 20297565 TI - [Osteoporotic sacral fracture--a painful condition, easy to miss. Sacroplasty a new treatment with quick pain relief]. PMID- 20297566 TI - [Mutational analysis of KRAS prior to targeted therapy in colorectal cancer. Quality control of molecular pathological methods in Sweden]. PMID- 20297567 TI - [Low-dosage ASA should not be given as primary prevention. The risk is greater than the benefit--also in high risk of cardiovascular disease]. PMID- 20297568 TI - [Acute gastrointestinal hemorrhage]. PMID- 20297569 TI - [Back at the starting point. Obesity patients the losers when sibutramine (Reductil) is recalled]. PMID- 20297570 TI - [The Sylf project for better generation shift in health care leadership. Who will be the boss after you?]. PMID- 20297571 TI - [Mammography screening should continue until full clarity of the effect is gained]. PMID- 20297572 TI - [New check list from Spur--a unique possibility to test the new internship]. PMID- 20297573 TI - [The director of internship studies important for the quality of education]. PMID- 20297574 TI - ["The Visby man's" skeleton testifies about severe pain]. PMID- 20297575 TI - [Mentally disabled who commit crime]. PMID- 20297576 TI - [Person-centered care--the clinician's comeback. The anamnesis and patient's symptoms in focus again]. PMID- 20297577 TI - [Appendiceal abscess: Uncertainty concerning the therapeutic principles. A survey indicates the need of randomized controlled trials]. PMID- 20297578 TI - [Acquired haemophilia--an overlooked disorder with high morbidity]. PMID- 20297579 TI - [Sexually transmitted infections. Good strategies can stop the increase]. PMID- 20297580 TI - [Chlamydia a common cause of miction problems]. PMID- 20297581 TI - [Strong increase of gonorrhea]. PMID- 20297582 TI - [Fewer young people born in Sweden have contracted HIV]. PMID- 20297583 TI - [Chlamydia and genital mycoplasma: epidemiology and risks]. PMID- 20297584 TI - [Threefold increase of Chlamydia in Dalecarlia--how could it happen?]. PMID- 20297585 TI - [Chlamydia test via Internet a good alternative to testing in clinics]. PMID- 20297586 TI - [The teenage brain, risk and sex]. PMID- 20297587 TI - [National Action Plan for Chlamydia Prevention]. PMID- 20297588 TI - [Can the medical profession accept insanity as a requirement for forensic psychiatric care?]. PMID- 20297589 TI - [Guidelines don't cover the therapeutic needs for everyone with inflammatory bowel disease]. PMID- 20297590 TI - [What determines successful heart transplantation care? Low volume alone does not explain the decrease in 1-year survival]. PMID- 20297591 TI - [Wide discussion about the Care Choice Stockholm necessary]. PMID- 20297592 TI - [Always hospital admission in TIA and stroke?]. PMID- 20297593 TI - The net effect of CER. PMID- 20297594 TI - Bungled payments. PMID- 20297595 TI - Technology. Data mining is vital as meaningful use looms. PMID- 20297596 TI - Bad debt. The rising tide of uncompensated care. PMID- 20297597 TI - Physician shortage. Doctor vacancies pose severe problem for children's hospitals. PMID- 20297598 TI - Other voices. What will it take to be a meaningful user? Interview by Bill Santamour. PMID- 20297599 TI - Emergency department. Hospitals aim to help patients pick an ED by posting wait times on the Web. PMID- 20297600 TI - The extra mile. A tremendous responsibility, a tremendous honor. Interview by Laura Putre. PMID- 20297601 TI - Pharmaceuticals. Disease foundations prime the drug pump. PMID- 20297602 TI - The new privacy norm. PMID- 20297603 TI - Who'll run your IT? AB - Hospitals already face a shortage of qualified health IT workers, a shortage that will only intensify with new HIPAA rules, the transition to ICD-10 coding and, most importantly, government pressure to ramp up EHRs. Many initiatives are under way to ease the potential crisis, but hospitals will have to be creative in cultivating talent and deploying limited staff and financial resources to generate the greatest return. PMID- 20297604 TI - Defining meaningful use. PMID- 20297605 TI - Do you hold staff accountable for safety? PMID- 20297606 TI - Power to the patient. PMID- 20297607 TI - Keeping a digital eye on patients. PMID- 20297608 TI - The fear factor. PMID- 20297609 TI - Awake fiberoptic intubation with target-controlled infusion of remifentanil in emergency surgery. PMID- 20297610 TI - Erem versus IV PCA meta-analysis. PMID- 20297611 TI - Pharmacokinetics of intranasal fentanyl spray in patients with cancer and breakthrough pain. AB - OBJECTIVE: This study reports the pharmacokinetics, tolerability, and safety of an intranasalfentanyl spray (INFS) in patients with cancer and breakthrough pain (BTP). DESIGN: A randomized, open-label, two-period, crossover trial. PATIENTS: Nineteen adult patients (mean 57.8 years) with BTP, receiving opioid treatment for chronic background pain, from clinical departments in Austria, France, and Norway entered and completed the study. INTERVENTION: Patients were randomly assigned to receive one of six INFS dose sequences: 50/100, 100/50, 50/200, 200/50, 100/200, and 200/100 microg. INFS was administered as a single dose in one nostril. Each dose was separated by a minimum of 48 hours. MAIN OUTCOME MEASURE: Plasma fentanyl concentrations were measured by high-performance liquid chromatography and tandem mass spectrometry from blood samples obtained at 0 (predose) and frequently up to 300 minutes after INFS administration. Blood pressure, peripheral oxygen saturation, and respiratory rate were assessed eight times during each of the two treatment periods. RESULTS: Mean fentanyl plasma concentrations increased in a dose-dependent manner, peaking for all fentanyl doses 9-15 minutes after INFS administration. Median T(max) values were 15, 12, and 15 minutes for the 50, 100, and 200 microg doses of INFS, respectively. Mean (SD) values for C(max) were 351 (+/- 226), 595 (+/- 400), and 1195 (+/- 700) pg/mL, respectively, indicating dose-proportionality. Six patients (31.6 percent) experienced adverse events during the treatment period, the majority being mild in severity. CONCLUSION: INFS at doses of 50, 100, and 200 microg showed a short T(max) and was well tolerated in patients with cancer. These results support INFS use in patients with cancer suffering from BTP. PMID- 20297612 TI - Variability of transdermal fentanyl metabolism and excretion in pain patients. AB - BACKGROUND: The rising popularity of the fentanyl transdermal patch and the striking number of deaths attributed to its prescribed use have brought attention to the large variability of fentanyl metabolism and the need for predictive models to prevent toxicity. OBJECTIVE: The purpose of this study was to determine the amount of both intrasubject and intersubject variability in fentanyl metabolism and excretion, using urinary excretion data from patients with chronic pain prescribed the fentanyl transdermal patch. METHODS: Liquid chromatography tandem mass spectrometry analytical technique was used to quantitate fentanyl and norfentanyl concentrations in spot urine specimens, after incubation with glucuronidase. Descriptive statistics and graphical analysis were conducted using Microsoft Excel 2007. Analysis was conducted on 206 subjects with > or = 2 visits listing transdermal fentanyl as current medication. Outliers and subjects with no detectable levels of drug were excluded, resulting in subject populations of 200 (all subjects analyzed) and 166 (subjects with drug concentrations above the instrument detection limit for all visits). RESULTS: The geometric mean metabolic ratio (MR) of norfentanyl to fentanyl was 6.2 x division by 2.4. A wide distribution was observed in total fentanyl load (1,000-fold) and MR (200-fold). The intersubject geometric standard deviation in MR was 2.4 (95% confidence interval [CI] for MR: 1-37) and the intrasubject geometric standard deviation was 1.8 (95% CI for MR: 2-20). CONCLUSION: The level of intrasubject variability over time in the pharmacokinetics of the fentanyl patch is much greater than previously observed and may be due to variability in absorption, interference of metabolism by concomitant medications, and variable metabolism due to genetic polymorphisms. The variation in the MR between subjects and within subjects may explain the unpredictable adverse effects observed with use of transdermal fentanyl. PMID- 20297613 TI - Oxycodone/acetaminophen at low dosage: an alternative pain treatment for patients with rheumatoid arthritis. AB - OBJECTIVES: To assess efficacy and safety of the association oxycodone/acetaminophen (oxycodone/acetaminophen) for pain treatment and disability improvement in patients with rheumatoid arthritis (RA). METHODS: Patients with RA (n = 29), suffering from moderate to severe pain for more than 3 months, were included in the study, except those under RA therapy with biological drugs. The treatment started with oxycodone/acetaminophen at the dosage of 5 mg/325 mg, and then the dosage was titrated until the attainment of good pain relief. Antiemetic and laxative therapy was used for the prophylaxis of known opioid-related adverse events. RESULTS: Patients continued their RA therapy without changing the dosages, reported reduced pain intensity and disease activity, and improvement of disability. Forty-two percent of patients had a good clinical response to oxycodone/acetaminophen treatment, according to European League against Rheumatism (EULAR) assessment criteria, and 50 percent of patients reached the American College of Rheumatology 20 percent improvement criteria (ACR20). At the end of the study, the mean (+/- SD) daily effective oxycodone/acetaminophen dose was 13.8 (+/- 6.8) mg/720.4 (+/- 291.0) mg. No serious adverse event was observed. Nausea, vomiting, and stipsis of mild moderate intensity were the most common adverse events. CONCLUSION: Oxycodone/acetaminophen at low dosages for the treatment of chronic pain in RA patients can be a good alternative to non-steroidal antiinflammatory drugs (NSAIDs), allowing the reduction of their consumption, while keeping RA therapy stable. PMID- 20297614 TI - The effect of intravenous opioid patient-controlled analgesia with and without background infusion on respiratory depression: a meta-analysis. AB - BACKGROUND: Although the addition of a background infusion for intravenous patient-controlled analgesia (IV-PCA) has been identified as a risk factor for the development of respiratory depression, this has not clearly been examined in a systematic fashion. The authors undertook a systematic review and meta-analysis of available randomized controlled trials (RCTs) to examine whether the addition of a background or continuous infusion to an IV-PCA regimen would be associated with an increased risk of respiratory depression. METHODS: Studies were identified by searching the National Library of Medicine's PubMed database (1966 to November 30, 2008). Inclusion criteria were a clearly defined analgesic technique of demand-only IV-PCA versus IV-PCA utilizing both a demand dose and background infusion, opioid medication used, and randomized trials. Data were abstracted and analyzed with the RevMan 4.2.7 (The Cochrane Collaboration, 2004). RESULTS: The search yielded 687 abstracts from which the original articles were obtained and data abstracted with a total of 14 articles analyzed. There were 402 subjects in the continuous IV-PCA with demand group versus the 394 subjects in the demand-only IV-PCA group. Addition of a background infusion to the demand dose for IV-PCA with opioids was associated with a significant increased risk for respiratory depression (odds ratio [OR] = 4.68, 95% confidence interval [CI]: 1.20-18.21). Subgroup analysis revealed that this increased risk was seen in adult but not in pediatric patients. CONCLUSIONS: Our meta-analysis indicates that the addition of a continuous or background infusion to the demand dose for IV-PCA is associated with a higher incidence of respiratory events than demand IV PCA alone in adult but not in pediatric patients; however, our overall results should be interpreted with caution due to the relatively small sample size and the wide range of definitions for respiratory depression in studies examined. PMID- 20297615 TI - Weaning of opioids and benzodiazepines at home after critical illness in infants: a cost-effective approach. AB - OBJECTIVE: To evaluate the feasibility of infants' weaning of opioids and sedatives at home. DESIGN: Retrospective observational study. SETTING: Level 3 pediatric intensive care unit. PATIENTS: Neonates treated for congenital diaphragmatic hernia (CDH) with extra corporeal membrane oxygenation (ECMO). INTERVENTION: Eligible infants were discharged early and further weaned of analgesics and/or sedatives at home. RESULTS: Of the 30 neonates treated for CDH with ECMO from 2003 to 2005, 15 survived. Five of these were weaned at home, on the guidance of telephone contact once a week. The mean infusion rates of morphine and midazolam for these children were significantly higher than those for other infants. Weaning at home took 11, 42, 107, 173, and 180 days, respectively, in the resultant mean savings on hospitalization costs per patient amounted to Euro150, 000. CONCLUSIONS: The results indicate that home weaning reduced the length of hospital stay by a median of 107 days for the five infants in this study, and thereby considerably reduced healthcare costs. Parents need to be informed clearly about possible withdrawal symptoms and should consent in this strategy. The strategy of final weaning with the aid of weekly telephone consultations with a consultant pediatric intensivist was feasible for these parents. PMID- 20297616 TI - Effect of preoperative rectal indomethacin on postoperative pain reduction after open appendectomy. AB - BACKGROUND: One of the major challenges faced by the treatment planning teams is how to manage postoperative pain. Previous studies agreed upon the effects of preoperative administration of nonsteroidal anti-inflammatory drugs on postoperative pain, but all have focused on patients with surgical noninflammatory diseases (ie, inguinal hernia or breast biopsy). The aim of this study was to evaluate the effects of rectal indomethacin on reducing postoperative pain in patients with acute appendicitis. METHODS: It is a simple randomized, clinical trial including 200 patients with acute appendicitis who were divided into two groups (A1 and A2). The case group (A1) received 100 mg rectal indomethacin during 2 hours before the operation. Pain intensity was assessed in all patients using a visual analog scale (VAS). Similarly, total dosage of meperidine analgesic medication and postoperative time to use of rescue analgesia were evaluated. RESULTS: Patients who received preoperative rectal indomethacin (A1) showed a significant reduction in the VAS score. Also, a reduction in total dose of meperidine and longer time to use of rescue analgesic medication were observed in A1 group. CONCLUSION: Preoperative administration of rectal indomethacin in acute appendicitis reduces postoperative pain. PMID- 20297617 TI - Use of sublingual methadone for treating pain of chemotherapy-induced oral mucositis. AB - Chemotherapy-induced and radiation-induced mucositis is a debilitating and often painful condition resulting in an inability to swallow, and thus inability to maintain adequate quality of life and overall functioning. To date, attempts on palliation of mucositis-related pain have primarily used topical anesthetic solutions and intravenous opioids; these approaches have achieved only limited success, particularly in oncology patients. The authors present a novel case of mucositis-related pain that is effectively treated with sublingual methadone. Sublingual methadone is an alternative to standard treatment options for mucositis-related pain and has unique pharmacokinetic and pharmacodynamic properties that make methadone a suitable agent for this pathology. These properties are addressed and discussed, as is the need for additional study to better understand the potential benefits, burdens, and risks that may be associated with this formulation of methadone when treating chemotherapy-induced and/or radiation therapy-induced mucositis in patients with cancer. PMID- 20297618 TI - Support for data standards GS1 Healthcare US maps out 2010 goals and beyond for supply chain. Interview by Bob Kehoe. PMID- 20297619 TI - Time well spent? Assessing nursing-supply chain activities. AB - The amount of time nurses spend providing direct patient care seems to be continually eroding. So it's little wonder a survey conducted last year of critical care, OR nurses and nurse executives found that half of the 1600 respondents feel they spend too much time on supply chain duties. Most also said their supply chain duties impact patient safe ty and their ability to provide bedside care. Experts interviewed for this report believe it's time for supply chain leaders and nurses to develop a closer working partnership. Included are their recommendations to improve performance. PMID- 20297620 TI - Wound care advancements bring bevy of products. AB - Over the past several years, the nearly $2 billion post-surgical woundcare market has been inundated with devices designed to accelerate healing and prevent infection. For materials managers, wound care nurses and others involved in product selection, keeping up with the changes can be a challenge. Here wound care experts, manufacturers and other sources highlight some of the many recent product advances and their applications. In addition, sources comment on the field of regenerative medicine and where it may be headed. PMID- 20297621 TI - Alert system fills critical need. AB - Developing a disaster preparedness program is just the start of being able to properly respond to supply chain emergency situations. The best plans evolve based on lessons learned during an actual event. The four-level program implemented at Aurora Health Care in Milwaukee shows how improved results can be achieved by focusing on communications. Their work before the second wave of the H1N1 influenza outbreak helped the organization avoid some of the product shortages and capacity strains so many other hospitals and health systems experienced. PMID- 20297622 TI - Endoscopes require constant care. Hospitals must remain vigilant: ECRI institute. AB - Some experts believe lapses in protocols for the cleaning and disinfection or sterilization of endoscopes occur more frequently than may be reported in the media. If so, this may increase the potential risk for endoscope cross contamination. The ECRI Institute, Plymouth Meeting, Pa., called attention to this issue recently by ranking the potential for cross-contamination of endoscopes the No. 1 technology hazard in its third annual report on the subject. But by establishing and executing proper protocols for endoscope reprocessing, hospitals can better manage this risk. PMID- 20297623 TI - Curbing infections via electronic surveillance. AB - Infection control programs can generate a wealth of data, but many professionals become overwhelmed when trying to translate the data into actionable knowledge. Automated surveillance systems have the potential to greatly streamline these efforts, but many questions arise about how to evaluate these systems, their costs, benefits and more. Here are answers to some of the most important questions on this issue. PMID- 20297624 TI - Valuable lessons learned from the patient's perspective. PMID- 20297625 TI - [Joy of creating]. PMID- 20297626 TI - [Analysis of oropharyngeal phase of swallowing in patients with amyotrophic lateral sclerosis]. AB - BACKGROUND: Dysphagia is a common symptom of amyotrophic lateral sclerosis (ALS) and leads to increased risk of aspiration, malnutrition and dehydration. Swallowing mechanism in ALS patients has not been systematically studied. MATERIAL AND METHODS: Based on the manometry analysis of upper investigate tract we have measured base of tongue contraction, resting pressure of the upper esophageal sphincter and average pharyngeal bolus velocity 10 ALS patients with slight dysphagia and have compared them to control group. RESULTS: All parameters measured were significantly changed in ALS patients indicting disturbances of oro pharyngeal phase of swallowing even in ALS patients with slight dysphagia. CONCLUSION: Early diagnosis of the swallowing disturbances is important for symptomatic therapy. PMID- 20297627 TI - [Visual evoked potential parameters in multiple sclerosis in developmental age]. AB - INTRODUCTION: Abnormal results of visual evoked potentilas (VEP) are typical for demyelinating diseases of the central nervous system, including multiple sclerosis. Elongation of P100 latency was the most frquent finding and sometimes changes in the shape of VEP responses or decrease of the amplitudes were observed. AIM OF THE STUDY: Results of VEP in children with multiple sclerosis. MATERIAL AND METHODS: 11 patients in the developmental age with multiple sclerosis were included, the age range was 13 to 17 years, 6 girls and 5 boys, hospitalized at Department of Pediatric Neurology Chair of Pediatric and Adolescent Neurology, Jagiellonian University in the years 2004-2009. The control group consisted of 11 children with analogous age range and sex distribution. VEP were recorded during monoocular visual stimulation with black and white checkerboard pattern reversal (pattern reversal VEP). The responses were recorded from three active electrodes O1, O2 and Oz (according to the international 10/20 electrode placement system). Latencies of maximum positive deflection P100, preceding N75 component and following N135 and amplitude of N75/P100 were analyzed. RESULTS: Elongation of P100 latency in the examined group was statistically significant when compared with controls. Differences of N75/P100 amplitudes did not differ statistically between the groups. CONCLUSIONS: VEP are one of the most important paraclinic tests used in diagnosis of MS in children. PMID- 20297628 TI - [Usefulness of electromyography in diagnostics of the neuro-muscular diseases]. AB - INTRODUCTION: Electrophysiological examinations still play an important role in initial diagnostics of neuromuscular disorders and monitoring of the disease progress or recovery process. AIM OF THE STUDY: Evaluation of neurophysiological examinations usefulness in differential diagnosis, indicating diagnostic and/or therapeutic management in patients with suspicion of neuromuscular disorders. MATERIAL AND METHODS: 109 patients were included, hospitalized at Department of Pediatric Neurology Jagiellonian University and treated at Neuromuscular, Neurologic, Orthopedic and Rehabilitation Outpatient Clinics of the Children's Hospital in Krakow. 6 groups of patients were indicated: I-11 patients with benign acute childhood myositis, BACM), II-18 children with gait disturbances, III-36 patients with suspicion of neuropathy, IV-11 patients hospitalized with suspicion of muscular disorders, V-18 children with SMA suspicion and V-15 patients with suspicion of myasthenia (MG). Neurophysiological examinations were conducted within 5 years (from May, 2004 to May, 2009) with Keypoint device from MedtronicDantec. RESULTS: In the first group, EMG examination, performed in the acute phase of the disease, did not reveal any abnormalities. Indicators of inflammatory process were normal, however in 5 patients transient elevation of CK was found. Diagnosis of BACM in this group was established. Couple-month observation of children after BACM did not reveal deficits of muscular tone and strength, recurrence of the disease, or elevation of CK, despite consecutive respiratory tract infections. In 4/18 patients with gait disturbances EMG examination revealed abnormalities. In 1 patient myogenic injury of the muscles was found, in 3 conduction in motor fibers of examined peripheral nerves was disturbed. In 14/18 children EMG examination did not reveal any pathological changes. In 17/36 children from group III diagnosis of inflammatory neuropathy was established (Guillain-Barre Syndrome, GBS), in 2 chronic inflammatory demyelinating polyneuropathy, and in 2 others multifocal motor neuropathy with conduction block. In 7/36 patients familial sensory-motor polyneuropathy was diagnosed. Neuroboreliosis was cause of neuropathy in 2 children. In 1 child, segmental inflammation of anterior horns of the spinal cord evoked by Coxackie virus was revealed. Friedreich disease, Nieman-Pick disease, thoracic outlet syndrome was found in others. In 1 boy symptoms of polyneuropathy and encephaloptahy occurred in the course of tal intoxication. In group IV EMG examination showed myopathic injury of the muscles in 9 children. In 2 others the examination results were normal. Kearns-Syre syndrome was found in one of them and Duchenne disease in the second one, 16, 5 years old boy without pain complaints, Becker disease in 2 and in next 2 patients encephalopathy and in rare cases BaCM, congenital dystrophy and myotubular myopathy. SMA was diagnosed based on clinical manifestation and EMG examination in 18 patients. EMG examination showed lower motor neuron injury in every child with SMA type I and II. MG was diagnosed in 15 patients based on clinical manifestation and positive result of fatigability test. Ocular myasthenia was found in 2 patients, bulbar type of MG was found in 1 and systemic myasthenia in 12 children. In electrophysiological fatigability test amplitude of the first response was normal in every patient and decrease of amplitude in response 4:1 in patients with MG was from 26 to 88%. CONCLUSIONS: Electromyographic examination remains important diagnostic tool of neuromuscular disorders. In order to limit extension of differential diagnostics EMG should be performed in its early stage. PMID- 20297629 TI - [The usefulness of posturography and caloric tests in selected neurological diseases]. AB - BACKGROUND: Many functions are disturbed after stroke. THE AIM: Of the research was to evaluate the usefulness of static posturography and caloric tests in the rehabilitation of postural stability disorders. MATERIAL AND METHODS: It was examined in 40 patients with cerebral stroke as compared with 40 healthy subjects. Based on selected stabilographic parameters it was investigated whether there is a difference in body deflection between patients and healthy individuals. The effect of visual control on stability was analyzed. The research was carried out with the use of static posturography and the standard set of tests. RESULTS: It has been shown that the postural stability of patients with stroke is characterized by a larger surface area of the stabilogram and a greater total length of deflection than of healthy individuals. It was observed that patients with stroke suffer the most significant deterioration of posture stability both with conscious visual control and without it. After examination of the patients before and after rehabilitation and having analyzed the coordination index, it has been proved that rehabilitation has a positive influence on the stability of posture in healthy controls. It has been proved that caloric tests performed in patients with damage to the central nervous system did not have an influence on the evaluation of the progress of rehabilitation. CONCLUSIONS: Post stroke postural stability disturbances are worsening without visual control and increased after rehabilitation. PMID- 20297630 TI - [Applicability of artificial neural networks in postoperative hearing improvement prognosis in patients with chronic otitis media]. AB - The primary objective of surgical treatment of chronic otitis media is to remove the pathological changes and restore the biology of the middle ear. Subsequently, ossicular chain reconstruction is performed in order to restore hearing. The aim of the study was to evaluate the efficacy of mathematical models (artificial neural networks) in postoperative hearing improvement prognosis. The models based on preoperative anamnesis and data concerning the operative procedure. The analyzed group comprised of 135 patients operated for chronic otitis media in the Department of Otolaryngology CM UJ in Krakow. The measure of postoperative hearing improvement was cochlear reserve (air-bone gap) closure depending on the type of ossicular chain reconstruction. The artificial neural networks provided 100% correct predictions basing on preoperative clinical examination, pathological changes found in the middle ear and description of the surgical procedure. The study proves that artificial neural networks are effective in functional result prognosis in tympanoplastic surgery. PMID- 20297631 TI - [Defects of facial nerve canal according to a character and localisation of lesions in middle ear]. AB - AIM: The aim of this study is the assessment the occurence of facial nerve canal (Fallopian canal) dehiscence in patients operated due to chronic medial otitis (depending on the location and type of inflammatory lesions) and in patients operated due to otosclerosis. Facial nerve paresis in patients with dehiscence found during surgery was also assessed. MATERIAL AND METHODS: The study group consisted of 456 patients operated at the Department of Otolaryngology at the University Hospital in Krakow, 359 due to chronic otitis media and 97 due to otosclerosis. Facial nerve canal dehiscence was found during surgery in 26 patients (6% of operated patients) more frequently in men. RESULTS: In most cases (54%) dehiscence was observed in patients with chronic medial otitis with cholesteatoma (27% with choleseatoma and 27% with cholestatoma and granulation), and equally (23% each) dehiscences were observed in patients with granulation and even in patients with otosclerosis and chronic simple otitis media. In over than half (54%) of patients with dehiscence inflammatory lesions involved all the middle ear spaces, in 15% the tympanic cavity, attic and antrum while in 4% of patients inflammatory lesions were limited to the tympanic cavity, attic or antrum. CONCLUSIONS: The facial canal nerve dehiscence is observed in majority in patients with cholestatoma and granulation, especially in tympanic region. In some cases its coexistence with circuit canals dehiscence. PMID- 20297632 TI - [Necessity of chorda tympani cutting from data collected at Department of Otolaryngology at the Collegium Medicum of the Jagiellonian University]. AB - BACKGROUND: Chorda tympani nerve is a branch of the facial nerve which enables perception of taste of 2/3 anterior part of tongue and it is responsible for unilateral parasymphatetic nerve supplying of the submandibular and sublinqual salivary glands. MATERIAL AND METHODS: Prospective analysis of patients operated on middle ear in ENT Department Jagiellonian University of Krakow between 2004 2008 was performed. Nearly 650 operations were done in that period of time. Chorda tympani nerve was cut in 96 individuals. Most of them were treated for chronic otitis media. RESULTS: When chorda tympani nerve was cut--the majority of cases did not complain of dysgeusia. Disturbance of taste was observed in ca. 2% of patients but it was transitory. The subject experienced sour/metallic taste. CONCLUSIONS: Taste disturbance following unilateral injury to the chorda tympani nerve was usually the most intense in the first few weeks and improves with time. PMID- 20297633 TI - [Signs of retinoblastoma]. AB - PURPOSE: Retrospective analysis of retinoblastoma symptoms in patients treated in Ophthalmological Clinic in Krakow. MATERIAL AND METHODS: A retrospective chart review was conducted of 293 retinoblastoma patients from our center (1969-2008). RESULTS: A total of 170 (58%) of 293 patients presented with leukocoria, 81 (27.6%) patients had strabismus, 22 (7.5%) had atypical sings, 12 (4.1%) was detected by chance. Eight (2.8%) patients who had a family history of retinoblastoma and were clinically screened for retinal tumors from birth were diagnosed younger. CONCLUSIONS: We recommend routine dilated fundoscopic examination by an ophthalmologist for early detection of retinoblastoma before leukocoria and strabismus. PMID- 20297634 TI - [Ocular outcomes in 3-year-old premature infants with retinopathy treated with cryotherapy and laser photocoagulation]. AB - PURPOSE: The aim of the study was to compare functional and structural outcomes in 3-year-old premature children treated in acute phase of retinopathy of prematurity with diode laser photocoagulation and cryotherapy. MATERIAL AND METHODS: We examined 106 premature children aged 3 years, treated for retinopathy of prematurity, by transpupillary diode laser photocoagulation (group II) or cryotherapy (group I). Functional (visual acuity using Snellen charts or preferential looking test - Teller acuity Card) and structural (anterior segment slit lamp and indirect Fison fundus examination) outcome and cycloplegic refraction using 1% Tropicamide were examined in all children. RESULTS: Favorable functional results occurred in 81.9% of eyes in patients after cryotherapy and in 83.9% of eyes in patients after diode laser photocoagulation. Structural outcome was favorable in 90.1% of eyes treated with cryotherapy and in 95.3% of eyes treated with diode laser photocoagulation. CONCLUSION: Diode laser photocoagulation appliance in retinopathy of prematurity treatment allows to obtain better functional and structural outcomes than cryotherapy. PMID- 20297635 TI - [Serum antiretinal antibodies (ARA) in patients with exudative age-related macular degeneration (AMD)--preliminary findings]. AB - BACKGROUND: Age-related macular degeneration (AMD) is the leading cause of blindness in the Western world. Despite the magnitude of this clinical problem, the pathogenesis of the disease remains still unclear. AIM: To determine the tissue specificity and titer of antiretinal antibodies (ARA) in sera of patients with exudative AMD. MATERIAL AND METHODS: Forty-six patients (92 eyes) 16 males and 30 women with exudative AMD were stratified arbitrary into four groups of AMD activity/severity: group I (n = 19)--patients with active choroidal neovascularization (CNV) in one eye and with drusen in the other eye; group II (n = 14)--patients with bilateral CNV; group III (n = 10)--patients with CNV in one eye and with disciform scar in the contralateral eye; group IV (n = 3)--patients with bilateral disciform scars. In all patients serum ARA were determined using indirect immunofluorescence detection on normal monkey retina as antigens substrate and FITC--labelled goat's anti-human IgA, G, M serum as the secondary antibody. RESULTS: In all patients' serum ARA were present in the range of titres from 1:40 to 1:5120. Control sera (n = 28, 28 males) demonstrated the presence of ARA in titres 1:10 to 1:40 in 46.4% cases. High serum titres of ARA characterized AMD patients with bilateral CNV and CNV in one eye and drusen in the contralateral eye. Low titres of ARA were detected in serum of patients with bilateral disciform scars. Indirect immunofluorescence (IIF) showed eight types histological patterns of patients' sera reactivity against retinal tissue. No correlation was found between serum ARA type and macular lesion activity. CONCLUSIONS: Our preliminary observations indicate a common presence of various ARA in serum of patients with AMD. Thus, it cannot exclude that ARA are involved in the pathogenesis or progression of AMD. PMID- 20297636 TI - [Vertigo and labyrinthine fistules at the patients operated on chronic otitis media]. AB - BACKGROUND: Otitis media is a frequent condition. Chronic infections of the middle ear can lead to defects of bony walls and development of complications. MATERIAL AND METHODS: We performed prospective analysis of patients operated on chronic otitis media in ENT Department Jagiellonian University of Krakow between 2004-2008. Nearly 650 operations on ears were performed in that period of time. RESULTS: Labyrinthine fistule was observed in 40 patients: 36 with COM, 3 with otosclerosis and 1 after head trauma. Vertigo was mentioned in ca. 30% of individuals in preoperative history. Labyrinthine fistule was usually noticed in the course of chronic cholesteatoma otitis media and chronic granulomatous otitis media and almost always it was located on lateral semicircular canal. In these patients defects of facial nerve bony canal were more frequent but the frequency of skull base defects was like in patients without labyrinthine fistule. The fistules were sealed routinely with a fragment of fascia. This procedure proved effective. PMID- 20297637 TI - [Migrainous aura subtypes in hospitalized children]. AB - INTRODUCTION: Migraine with aura is characterized by reversible focal neurological symptoms preceding or accompanying headache. Visual aura is the most common type of aura and its patognomic symptoms are scintillating fortification migrating across the visual field or scintillating scotoma. However, the symptoms are not always so typical and clinical doubts are greater when negative symptoms (loss of vision, numbness or paresis) are present. Differential diagnosis of migraine with aura includes in the first place transient ischemic attack (TIA) as well as epilepsy. Diagnosis of migraine in the developmental age is more difficult and associated with unprecise description of the symptoms. Thorough history taking is crucial in migraine diagnosis and following management. Knowledge of migraine with aura symptoms, clinical differences associated with developmental age and features enabling differentiation with other disorders imitating migraine is very important. AIM OF THE STUDY: Description of aura types and characteristics of migraine headache and their accompanying symptoms in children. MATERIAL AND METHODS: 30 children were included, aged 8-17 years (mean 13,6 years), hospitalized at Department of Pediatric Neurology Chair of Pediatric and Adolescent Neurology, Jagiellonian University in 14 months of years 2008 and 2009. Clinical analysis was based on inquiry addressed to the patients and their parents. RESULTS: Migraine with visual aura was established in 9 patients, with somatosensory aura in 4, visual and somatosensory in 5, visual and dysphasic in 1, visual, somatosensory and dysphasic in 5, somatosensory and dysphasic in 2 and basilar type migraine in 4 patients. Consequently, symptoms of visual aura were present in 20/30 patients, in 9 of them it was the only type of aura and in 11 coexisted with other aura types. In more than half cases it manifested as simple visual phenomenons (spots, dots, frills, lines). Blurred vision was found in 5 patients (bilateral in 3, unilateral in 3) and hemianopia in 2 (bilateral in aura was observed in 16/30 patients and only in 4 of them it occurred without other aura symptoms. Dysphasic aura accompanied other aura types in 8 cases. Basilar type migraine was established in 4 patients. Unilateral migrainous headache occurred in 20/30 patients. Pain intensity was defined as very severe, severe and moderate in the following 10, 12 and 8 patients. Pulsating quality of the pain was found in 15 cases. Aggravation of headache by movement was observed in 22/30 patients. Nausea was the most common accompanying symptom present in 20/30 patients. Vomiting, photophobia and phonophobia occurred in 15 patients each. Coexistence of nausea and/or vomiting, photo- and phonophobia was reported in 12 cases. Vertigo and balance disturbances were frequently found additional symptoms and occurred in 11 and 2 patients and in 6 coexisted together. Positive family history of migraine was reported in 18/30 patients. CONCLUSIONS: 1. Visual and somatosensory aura were the most frequent types of aura in children; basilar-type aura occurred with the lowest frequency. 2. Unilateral headache with severe or very severe pain intensity, aggravated by movement was found in more than half cases. Pulsating quality of headache was present in half of the patients. 3. Accompanying symptoms (nausea, vomiting, photo- and phonophobia) occurred in the combination, fulfilling ICHD II diagnostic criterion D for migraine in less then half cases. Vertigo and/or balance disturbances, were commonly found symptoms with no association to aura type. 4. Familial occurrence of migraine was reported in more than half patients. 5. Another modification of migraine diagnostic criteria for children is needed. 6. History takes crucial role in the diagnosis of childhood migraine. PMID- 20297638 TI - [Value of the experiment for developmental neurology]. AB - Some neurological diseases cannot be at present efficiently treated, because of their unknown pathogenesis and the lack of appropriate drugs. The etiology of autism is not known and there is no drug for ameliorating basal symptoms of this disease. Some research was conducted to obtain an adequate rodent model of autism in which potential drugs can be studied. Therapeutic action of psychostimulant drugs in the attention deficit hyperactivity disorder (ADHD) are known for years, but because of their addictive properties, decision about their clinical use in a child is not easy. The precise recognition of their mechanism of action and determination of the maximal but safe doses should facilitate making the correct decision. Only about 70% children suffering from epilepsy are efficiently treated with one drug, while in the remaining the use of two or more drugs is necessary, which increases the the risk of side effects. Clinically more effective classical antiepileptic drugs can disturb cognitive functions in the child, therefore, on the basis of the present knowledge the experiments are under way with the aim of receiving drugs with strong anticonvulsant properties but without serious side effects. The introduction of efficient neuroprotective drugs, which may ameliorate secondary neuronal cell damage in various brain regions to the therapy is the main aim of numerous experimental works. At present it seems that neurotrophic factors can be useful but they must be administered centrally. Transplantations of transfected cells capable of producing neurotrophic factors or stem cells to the brain may be in the future an efficient method for improving brain function. PMID- 20297639 TI - [Drug resistance in epilepsy]. AB - BACKGROUND: Although there are numerous definitions of drug resistance in epilepsy it is generally accepted that drug resistance occurs when seizures persist in the presence of an optimal antiepileptic treatment. In spite of many newer antiepileptic drugs introduced into treatment, the relative number of drug resistant patients remains approximately the same and reaches 30%. Consequently, there are a great deal of experimental and clinical studies aimed at finding mechanisms responsible for this phenomenon. Characterization of these mechanisms could result in new, more efficient treatment strategies. THE AIM OF STUDY: To review experimental and clinical data on possible mechanisms of drug resistance in epilepsy. RESULTS: An increased expression of protein drug transporters (for example, P-gp or MRP) within the blood-brain barrier or in the epileptic focus itself seems an important mechanism of drug resistance. This leads to the enhanced removal of antiepileptic drugs from the brain and subsequently, their reduced concentrations in the target tissue. Also, mutations of genes encoding GABAA receptors or ion channels may be reasons for the diminished protection of antiepileptic drugs. Some role may be ascribed to the genetic polymorphism of liver microsomal enzymes. Last but not least, use of other drugs unrelated to epilepsy (i.e. theophylline) or ingestion of stimulatory substances (f.e. caffeine) are likely to reduce the protective potential of antiepileptic drugs. CONCLUSION: In animal models of epilepsy, inhibitors of drug transporters (verapamil, probenecid) efficiently inhibit drug resistance--may be, this potential method of treatment will be positively verified in clinical trials. Initial clinical data on this issue are encouraging. Probably, the drug resistance due to methylxanthines could be stopped quite easy by replacement of this drug group with other drugs sharing other mechanisms of action and exerting similar clinical effects. The most challenging for an efficient treatment seems drug resistance due to genetic reasons. PMID- 20297640 TI - [Dry eye syndrome and allergic conjunctivitis--epidemics of XXI century- diagnostic problems and management]. AB - Recently, allergic conjunctivitis and dry eye syndrome have been thought to be the epidemics of XXI century. Allergic conjunctivitis is the commonest form of allergy worldwide. Clinical symptoms of dry eye are the most common cause of patients complains in out-patient ophthalmological clinics. Both, allergic conjunctivitis and dry eye syndrome, may be associated with some systemic diseases. Thus, it is crucial to perform complete allergic tests in patients suspected of allergic conjunctivitis. The assessment of IgE in tears is a very sensitive test in these cases because physiologically this immunoglobulin is not detectable in tear film. In cases of dry eye syndrome the measurement of tear osmolarity has been is thought to be the most specific and sensitive test, recently. PMID- 20297641 TI - [Guidance for the treatment of neovascular age-related macular degeneration (AMD)]. AB - BACKGROUND: Neovascular age-related macular degeneration (AMD) is becoming an increasing socio-medical problem as the proportion of the aged population is continuously increasing. However, new researches in the pathogenesis of the disease offer the opportunity to develop more effective therapies of AMD. AIM: This article will focus on the options in the management of neovascular age related macular degeneration and recent therapeutic options. RESULTS: The recent development of anti-VEGF (vascular endothelial growth factor) substances for use in clinical routine has markedly improved the prognosis of patients with neovascular AMD. Intravitreal treatment with substances targeting all isotypes of Vascular Endothelial Growth Factor (VEGF), for the first time results in a significant increase in visual acuity in patients with neovascular AMD. The combination with occlusive therapies like photodynamic therapy (PDT) potentially offers a reduction of re-treatment frequency and long-term maintenance of the treatment benefit. Further developments interacting with various steps in the angiogenic cascade are under clinical or preclinical evaluation and may soon become available. CONCLUSION: Nevertheless, the growing number of novel therapeutic options will have to provide proof of concept in randomized controlled clinical trials. PMID- 20297642 TI - [Visual perception deficits of cortical origin]. AB - This work comprises of a literature review on visual perception distortions that have their origin in structural or functional irregularities of the brain, resulting in the cortex malfunction. The main area that we pay attention to is the brain cortex, but we should not forget, that diseases destructive to the lower brain structures also inevitably lead to secondary dysfunction of the cortex, and thus they have also been included in this paper. Cerebral vision disorders are a small percentage of caseload in either neurology or ophthalmology practice, yet they certainly are interesting for the cognitive scientists, as they open a window into the complex mechanisms of the cerebral clockwork. We are presenting examples of disorders, many of which engage the creative cooperation between specialists from different fields of neuroscience. Three kinds of disorders are presented: vision loss, agnosias and hallucinations. Among others there is some information on cortical blindness, blindsight, Anton's syndrome, hysterical blindness, apperceptive and associative agnosia, prosopagnosia, pure alexia, achromatopsia, Bonnet syndrome, Alice in Wonderland syndrome, peduncular halucinosis etc. PMID- 20297643 TI - [Causes and diagnostics of dizziness of central origin in children]. AB - Dizziness and vertigo are symptoms caused by several etiological factors, they are result of general diseases, within anemia. They are associated with several diseases of the organ of hearing and balance, which are under laryngological care, and one of most important tests to distinguish vertigo of central and peripheral origin is videonystagmography. Several diseases of the central nervous system cause instability of posture and gait. Psychogenic feeling of being insecure and unsafe makes the diagnostics more complicated. Vertigo of central origin in children can be a first symptom of severe conditions, such as tumor of CNS, therefore the neuroradiological evaluation is necessary for early diagnosis, before the occurrence of increase of intracranial pressure symptoms. Vascular diseases, such as vertebro-basilar insufficiency or stroke are diagnosed more common in adults, still they are not excluded in children, and therefore vascular evaluation is necessary. The cerebrovascular ultrasound is a method significant in the diagnostics as well as in the monitoring of therapy of cerebral vascular diseases. The elecrophysiological evaluation, EEG or videoEEG is useful in the evaluation of paroxysmal conditions. Evoked potentials are helpful in diagnostics of demyelination of CNC. The serological tests (within to detect boreliosis) are infrequently performed; they may lead to correct diagnosis and causal treatment. The paper presents examples of diagnostic methods valid in children with dizziness of central origin. PMID- 20297644 TI - [Children's sleep disturbances in videoelectroencephalography and polysomnography -preliminary data]. AB - INTRODUCTION: Correlation between sleep and epilepsy is one of the most basic issues of pediatric neurology. VideoEEG nad polysomnography play an important role in diagnostic process of seizures occuring during sleep, epileptic seizures as well as parasomnic episodes. AIM: In this paper videoEEG and polysomnography assessment in diagnosis paroxysmal sleep events in children was done. MATERIAL AND METHODS: 25 sleep registrations were performed, videoEEG was performed in 23 children with the age limit of 5 years, and two 8-years-old children underwent total polysomnographic examinations. RESULTS: Examination during sleep time enabled to establish diagnosis of epilepsy in 18/25 children, in 2 children suspicion of epilepsy was made and in 5 epilepsy was excluded. Positive video results were found in 18/25 children and in 7 no clinical symptoms were recorded. Paroxysmal EEG activity was registered in 16 children, in 5 it was abnormal and in 4 it was within normal limits. Frontal epileptic seizures were observed in two children with simultaneous pathological changes in EEG, and in 1 of them in polysomnographic recording. CONCLUSIONS: VideoEEG and polysomnographic examinations in children during sleep are helpful in defining seizure types and parasomnias. PMID- 20297645 TI - [Rehabilitation outcome in children with cranial trauma and hypoxaemia of the brain]. AB - BACKGROUND: Traumatic brain injury is one of the most common causes of children's disability and death. AIM OF THE STUDY: The goal of this study was to present the effects of improvement treatment in patients who suffered various types of brain trauma, to discuss their motor functions as well as the emotional state and behavioural disturbances. One of the aims was also to present complications which took place reagardless of complex rehabilitation. MATERIAL AND METHODS: In this study we describe the state of 5 patients. The patients were assessed with the Ashworth and RLAS scales before and after the complex rehabilitation. The programme of rehabilitation was designed individually for each patient depending on his RLAS score. The complications developed after 6 months of treatment are described. RESULTS: In one case only- in a girl with hemiparesis- the state of nearly independent motor functioning was achieved. The other patients are bedridden or dependent on a second person when moving in a wheelchair. The girl with hempiparesis and another girl with spastic quadriparesis remain in the best verbal contact. Both of them however present with profound cognitive, emotional and behavioural deficits. The other patients are unable to reach any verbal communication. Because of swallowing problems some of the patients had feeding tube or tracheostomy performed. Each patient had an individually designed rehabilitation programme. CONCLUSIONS: The outcome of rehabilitation treatment in patients with profound traumatic brain injury is very individual. The best outcome was achieved in a girl with hemiparesis who suffered brain injury in a car accident, and worse in children after brain hypoxaemia. PMID- 20297646 TI - [Meningeal empyema--still actual topic]. AB - Pus collection between dura matterand arachnoidis not an abscess but an empyema. Complains of severe headache, a lack of cooperation is observed, sometimes high fever, seizures, which may lead to an epileptic like condition. Patient gives an impression of a severely ill person. We report four different cases of intracranial complications, in the form of dural empyema diagnosed and treated in our Department. In the pre antibiotic therapy era, cerebrospinal meningeal empyema inevitably led to paralysis, paresis and death. PMID- 20297647 TI - [Cysts of the orbital bone and orbital sinus: clinical and morphological characteristics of the three cases]. AB - BACKGROUND: Solitary bone cyst is rarely situated in facial bones. AIM: We discuss clinical view, results of radiological examinations and differential histopathological diagnostics of cases. RESULTS: We present 3 cases of patients: 51 year old man with cyst in frontal sinus; 29 year old man and 46 year old woman -both with changes in bones of the orbit. In all the cases results of histopathological examinations were similar. Cystic-shape pieces of vascularizated connective tissue were observed. Multiple cracks filled with cholesterol, macrophages with hemosiderin and occasionally multinuclear cells were noticed. CONCLUSIONS: Solitary bone cyst may be located in the periorbital bone, especially frontal. Excellent laryngological, optic and cosmetic results are results of the surgery. Suspicious of the solitary bone cyst is possible due to MR or CT imaging, but final diagnosis must be confirm by histological examination. PMID- 20297648 TI - [Quorum sensing regulation in pseudomonas]. AB - Expression of many bacterial genes is regulated in a cell density-dependent manner via small signal molecules known as autoinducers; this type of regulation is termed quorum sensing (QS). The QS systems that employ N-acyl-homoserine lactones (HSLs) are best understood in Gram-negative bacteria. QS regulates expression of various genes, including the genes responsible for the production of virulence factors, synthesis of exoenzymes and antibiotics, antagonistic properties of bacteria, etc. The QS systems of the genus Pseudomonas are linked to other global regulatory networks of the cell, and their functions are controlled by numerous additional regulatory factors. Such regulators and the QS systems together form an intricate multifactorial cascade regulatory network. The review considers the QS systems of several Pseudomonas species, their interaction with other regulatory systems, and their roles in the regulation of cell processes. PMID- 20297649 TI - [Interspecific migration and evolution of bacteriophages of the genus phiKZ: the purpose and criteria of the search for new phiKZ-like bacteriophages]. AB - Some properties of bacteriophages with large (200 kb and more) sequenced genomes have been compared. In contrast to other large bacteriophages from different families, bacteriophages active on pseudomonads of various species (phiKZ-like bacteriophages) have some common features, which suggests their phylogenetic relationship and independence of their evolution as a result of migration among bacteria of this family. Among such common features are the absence in the genomes of these phages of sites sensitive to endonuclease PstI, the absence of genes encoding DNA polymerases that are similar to the known enzymes of this type, possible dependence of replication of the phage genome on bacterial DNA polymerase, and a considerably larger average gene size as compared to that for other phages. Criteria are suggested for searching for novel phiKZ-like bacteriophages: the size of a phage particle, production by bacteria infected with such phages of a large amount of highly viscous mucus. Taking into account the use of these bacteriophages in therapeutic preparations (due to a broad spectrum of lytic activity) and a poor knowledge of a majority of their gene products, it seems necessary to perform a more comprehensive genetic analysis of phages of this genus or their mutants for selecting those adequate for phage therapy. PMID- 20297650 TI - [Genetic markers of melanoma]. AB - Melanoma is among the most aggressive malignancies. Tumors with a thickness of 4 mm can produce metastases, and the mean survival of the patients is 9 months. The review presents modern classification of the melanoma types based on cytological and morphological indices (Clark model). Alterations of genes in melanomas are discussed in detail. These genes include tumor suppressors, proliferative response genes (oncogenes), and transcription factors. Alterations in the Wnt signaling, MAPK cascade, and Fas signaling pathways are considered. Changes in the mismatch repair (MMR) genes are also analyzed. From practical perspective, understanding the genetic alterations provides identification of potential targets for therapeutic exposure and enables prognosis of the tumor response to chemotherapy. PMID- 20297651 TI - [Dynamics of the spatial organization of the chromosome set in cells of Drosophila melanogaster imaginal disks normally and under the action of the tumor inducing mutation Merlin]. AB - Fluorescence of H3-p histone and DAPI was studied at different stages of interphase and mitosis in cells of imaginal disks of third-instar Drosophila melanogaster larvae. Three stages differing in the spatial organization of the chromosome set in mitosis were revealed. At the first stage (prophase, prometaphase), the histone 3 phosphorylation level rises, and the volume occupied by the chromosome set in the nucleus increases. The distinctive features of the second stage (metaphase) are a gradual decrease in the histone 3 phosphorylation (the density ofphosphorylation remaining constant) and a reduction of the volume occupied by the chromosome set. At the third stage (anaphase, telophase), the intensity and density of the signal from H3-p histone decrease, and the volume occupied by the chromosome set reduces. At this stage, in Mer4 larvae, in contrast to the control strain, the cells prematurely pass from anaphase into telophase. In addition, a subpopulation of cells with an abnormally large volume of nuclear DNA during the G1 period was revealed in Mer4 larvae. The cells of this subpopulation do not enter into the DNA synthesis and quit the cycle. PMID- 20297652 TI - [Effect of mutations in Drosophila melanogaster tumor suppressor Merlin on proliferation and differentiation of wing cells]. AB - Experiments on transplantation of wing imaginal discs homozygous for a mutation in the tumor suppressor gene Merlin have demonstrated that this mutation does not induce malignant tumors. Marking of the wing disc compartment borders by specific antibodies showed the absence of essential compartment border defects in case of the Merlin mutation. Drosophila melanogaster cells mutant for Merlin have shorter cell cycle than normal cells. Proliferation of imaginal discs lasts longer in case of the mutation. It is known that beginning from some moment of development, wing veins serve as clonal restriction lines that cannot be crossed by growing mosaic clones. We showed that the Merlin mutation leads to depression of vein clonal restriction property. This means that this gene is involved not only in the control of cell proliferation, but also in the control of cell mobility and adhesion. PMID- 20297653 TI - [The Rdh54 protein role in regulation of DNA repair in yeast Saccharomyces cerevisiae]. AB - In this work, we present the evidences of the involvement of Rdh54 in coordination of DNA repair by several pathways. Previously, we isolated rdh54-29 point mutation demonstrating unique properties different from the full deletion of RDH54 gene. Epistatic interaction between rdh54-29 and apn1delta mutations discloses the function of Rdh54p in the process of base excision repair. However, rdh54-29 mutant exhibits sensitivity to many DNA damaging agents including UV light, methylmethanesulphonate and nitrous acid. Such pleiotrophic effect of rdh54-29 mutation may indicate the role of Rdh54p in the regulation of different DNA repair systems. To check this hypothesis, we estimated the effect of rdh54-29 mutation on recombination and mutagenesis. The data confirm the involvement of Rdh54p in coordination of different DNA repair systems including mutagenic and recombinagenic pathways as well as nucleotide excision repair. Rdh54p presumably operates via chromatin remodulation at the site of damage rendering DNA accessible to the DNA repair enzymes. PMID- 20297654 TI - [Comparative analysis of thermotolerance of sunflower chlorophyll mutants]. AB - The influence of high temperatures on sunflower chlorophyll mutants was studied. The tolerance criteria were the level of chromosome aberrations and the mitotic index in the root apical meristem of seedlings, the level of nucleus-free cells in the epidermis of cotyledonous leaves, and the intensity of chlorophyll accumulation after the action of heat shock (HS). In addition, the frequency of plants with an altered content of pigments in M1 and M2 was analyzed. The results indicated that the plastomic mutant en-chlorina-5 is more tolerant to temperature stress as compared to other sunflower lines. PMID- 20297655 TI - [Molecular cytogenetic characterization of spring triticale line 131/7 carrying a rye-wheat translocation]. AB - The chromosomal composition of the spring triticale line 131/7 carrying a rye wheat translocation was studied using GISH, C-banding, and SSR analysis. The complex analysis revealed the presence of a pair of 2D chromosomes and T2RS.2RL 2BL translocation in the genome of the hexaploid triticale line 131/7. The break point in the translocated chromosome is between the markers Xwmc592 and Xwmc441, loci 63.9 cM and 76.8 cM on the linkage map (Wheat, Consensus SSR, 2004 NA-SSR 2004-2B) and in the region C2BL2-0.36 on the physical map (Wheat, Physical, SSR). The analysis of the line enables its use in breeding programs and in genetic studies. PMID- 20297656 TI - [Correlation between morphological and genetic differentiation in Cuban hutia (Rodentia, Capromyinae): species fragmentation on the area and the problem of excessive taxonomic status problem]. AB - The work attempts to explain the previously discovered phenomenon of excessive taxonomic status of the species and subspecies of Cuban hutias relative to their protein genetic divergence. The reasons underlying the fragmentary distribution of the species belonging to the family Capromyidae over the Antilles and Bahamas is also considered. Samples of four geographically distant hutia (genera Capromys and Mysateles) populations inhabiting different biotypes were assessed according to 32 allozyme loci. It has been demonstrated that the interpopulation and subspecies differentiation in the gene frequencies in these genera is very low. As for the pattern of polymorphism (Shannon?s measure), the populations and subspecies within these genera are well differentiated and adequate to their morphological differentiation. This suggests that the genetic divergence pattern of hutias in post-Pleistocene was predominantly determined by selection on the background of a relatively rapid formation of multiple morphotypes. It is assumed that the evolution within the family Capromyidae in the earlier and the later periods was associated with the geomorphological and climatic events in the history of the Earth. This standpoint provides for explaining the phenomena of both the excessive taxonomic status of the Cuban Capromyinae and the fragmentary distribution of these species over the Antilles and Bahamas, amazing at a first glance. PMID- 20297657 TI - [Phylogeography of southern Asian Dolly Varden char Salvelinus malma krascheninnikovi: genealogical analysis of mitochondrial DNA]. AB - Phylogeography of southern Asian Dolly Varden char was studied using the data on mtDNA variation (regions ND1/ND2, ND5/ND6, and Cytb/D loop) obtained using PCR RFLP analysis. Analysis of contemporary population genetic structure showed that S. m. krascheninnikovi throughout the whole species range was characterized by high population differentiation in combination with rather small differences between the populations from remote regions. The genealogy of mtDNA haplotypes was reconstructed and nested clade analysis of geographical distances was performed. Geographical distribution of mtDNA haplotypes of S. m. krascheninnikovi was explained by population genetic processes (restricted gene flow), as well as by historical demographic events (range expansion and fragmentation). It was demonstrated that the main demographic events were associated with cyclic processes of the geological formation of the Sea of Japan and adjacent territories. Furthermore, genealogical tree of S. m. krascheninnikovi contained the traces of secondary contact between isolated phylogeographical lineages. PMID- 20297658 TI - [The genotypy structure of a natural Daphnia population based on the phenotypic response on change in the amount of food]. AB - Natural populations of Daphnia are genetically heterogeneous with regard to phenotypic response to modification in the food quantity (a set of metric quantitative traits). In the majority of the traits, three genetically determined response types to the environmental factor studied have been detected: arithmetic means decrease (R1), increase (R2) or remain constant (St) as a result of a decrease in the food quantity. This phenotypic response was shown to occur in the whole set of the metric traits studied, irrespective of physiological specialization. The problems of assessment of genetic population structure based on phenotypic response of the individuals reflected in quantitative traits are discussed. PMID- 20297659 TI - [Population demographic structure of the city of Ulan Ude: ethnic composition and age at marriage]. AB - The marriage structure of the population ofUlan Ude, the capital of Buryat Republic, which is characterized by a mixed ethnic composition, has been studied. Differences between Ulan Ude districts in a number of genetic demographic parameters have been found. In ethnic terms, the city district populations differ from one another in the number of ethnic groups and the proportions of the largest groups (Russians and Buryats). In the total Ulan Ude population, the proportions of Russian men and women among persons contracting marriages are 71.44 and 73.79%, respectively; those of Buryat men and women are 23.36 and 22.79%, respectively. The total proportion of all other ethnic groups among both men and women contracting marriages is no more than 5.2%. The mean ages at first marriage in both indigenous and immigrant populations of Ulan Ude are relatively old; these values are 25.9 and 24.72 years for Buryat men and women and 24.86 and 22.69 for nonindigenous men and women, respectively. PMID- 20297660 TI - [Syntropic genes of allergic diseases]. AB - Common (syntropic) genes of allergic diseases (ADs) HLA-DQB1, HLA-DRB1, IL4, IL4RA, MS4A2, HLA-DQA1, LTC4S, IL13, IL10, and TGFBL have been identified on the basis of information from the HuGENet internet database. The functional sphere of competence of these genes is associated mainly with the initiation and regulation of an immune response and inflammation. Importance of these processes in the development of ADs is underlined. The results of cluster analysis of allergic diseases obtained using the data on common genes predisposing to their development are presented. Genetic clusterization ofADs confirms their accepted clinical classification. PMID- 20297661 TI - [Analysis of genetic predisposition to pulmonary tuberculosis in native Russians]. AB - Tuberculosis (TB) is one of the most important concerns of public health. There is evidence suggesting that genetic status is responsible for predisposition to infectious diseases including TB. To determine genetic risk factors of TB development, the frequencies of polymorphisms of genes CYP1A1, CYP2D6, CYP2C9, CYP2C 19, GSTT1, GSTM1, NAT2, MDR1, and NRAMP1 in 73 TB patients and 352 healthy individuals were determined by allele-specific hybridization using microarray technology. The TB patients have shown a significant increase in the frequency of the null GSTT1 genotype (OR = 3.26, 95% CI = 1.91 - 5.55, p = = 0.000028) as well as the double null GSTT1/GSTM1 genotype (OR = 4.05, 95% CI = 2.14 -7.65, p = = 0.000034) compared to the group of healthy donors. It was shown that the NAT2*5/*5 genotype in combination with the "null" GSTT1 and the double "null" GSTT1/GSTM1 genotypes was observed significantly more often in the TB patients than in the control sample. Thus the examined GSTT1, GSTM1 and NAT2 gene polymorphisms may potentially alter the risk of TB development in ethnic Russians and are of interest for further research using larger cohorts of patients. PMID- 20297662 TI - [Effect of harvesting on the genetic diversity and dynamic behavior of a limited Mendelian population]. AB - A mathematical model of the changes in the size and genetic diversity of a harvested, single-locus Mendelian population under the conditions of density dependent selection is analyzed, with a special emphasis on the possibility of conserving or loosing polymorphism as a result of equilibrium harvesting. It is demonstrated that harvesting leads to changes in intrapopulation parameters under the conditions of density-dependent selection; as a result, the genotypes that were the least fit in an unharvested population will prove more fit, the genetic composition of the population at equilibrium being changed accordingly. Thus, harvesting may, under different conditions, either conserve or reduce the genetic diversity of the population. PMID- 20297663 TI - [Expression of early developmental genes in vole Microtus rossiaemeridionalis]. AB - The expression of genes Sox2, Klf4, Myc, Sall4, Gata6, Foxa2, Hnf4a, Cdx2, Esrrb, Hand1 in cultivated cells, embryos and organs of adult voles Microtus rossiaemeridionalis was studied. High resemblance of the expression patterns of these genes in the organs of adult voles, mice and humans was demonstrated. It was established that genes Gata6, Foxa2 and Hnf4a were specifically expressed in vole extraembryonic endoderm cells, while Cdx2 and Handl genes, in trophoblast stem cells. This shows that these genes can be used markers for corresponding vole cell lines. Indirect confirmation pointing to the fact that Oct4 gene is a marker gene for epiblast cells both in the vole and mouse was obtained. PMID- 20297664 TI - [Comparative-enzymological study of cholinesterase of the Pacific squid Todarodes pacificus]. AB - Summarized are results of the 40-year studies of the Russian biochemists on the comparative-enzymological characteristics of cholinesterase of optic ganglia of the Pacific squid Todarodes pacificus. The review includes the comparative evaluation of the cholinesterase activity of various hydrobiont tissues, the proof of enzymatic homogeneity of the tissue of the Pacific squid optic ganglia, data on substrate specificity with study of 18 ester substrates as well as detailed study of inhibitory specificity (61 irreversible inhibitors and 49 reversible onium inhibitors). Peculiarity of properties of this enzyme as compared with vertebrate and invertebrate cholinesterases is shown. PMID- 20297665 TI - [Taurine. Effect on exotrophia and metabolism in mammals and fish]. AB - Data have been presented on the taurine content in various mammalian and fish tissues as well as on pathways of its formation, turnover, and numerous functions. Based on comparison of the character of the taurine effects on various animal functions as well as of the fact of the presence of taurine in the more ancient by origin potential objects of the mammalian and fish nutrition, it is suggested that the taurine polyfunctionality has appeared at different stages of the biota. PMID- 20297666 TI - [Activity of detoxifying and antioxidant enzymes in the pond snail Lymnaea stagnalis (gastropoda: pulmonata) during invasion by trematode cercariae]. AB - A comparative analysis of changes of activities of detoxifying and antioxidant enzymes was carried out in the body homogenate of the pond snail Lymnaea stagnalis. Juvenile snails with the shell size of 4-6 mm were infested with cercariae of one (Echinoparyphium aconiatum or E. recurvatum or Moliniella anceps) or two (E. aconiatum +M. anceps or E. aconiatum + E. recurvatum or E. recurvatum + M. anceps) trematode species. It has been revealed that activities of detoxifying and antioxidant enzymes in the body of the snail L. stagnalis change at invasion with trematodes and that the character of the changes depends on the stage of development of the trematodes in the host body, the variant of infestation (monoinvasion or mixed infestation), and the species of the parasite. The first 2 h after penetration of the trematode cercariae into the molluse tissues is accompanied by an increase of activities of the detoxifying and antioxidant enzymes. A long coexistence of metacercariae in the host body (no less than for 13 days) is accompanied by a decrease of activities of non-specific esterases and glutathione-S-transferase and by an increase of superoxide dismutase. PMID- 20297667 TI - [Generation of reactive oxygen species and activity of antioxidants in larva hemolymph of galleria mellonella (L.) (lepidoptera: piralidae) at development of process of encapsulation]. AB - Activities of enzymatic antioxidants (superoxide dismutase, glutathione-S transferase, and catalase) have been determined in hemocytes and generation of reactive oxygen species (ROS) has been studied in lymph of larvae of the wax moth Galleria mellonella at development of the process of encapsulation of nylon implants. It has been established that as soon as 15 min after piercing of cuticle with implant the capsule is formed on its surface. The active melanization of the capsule has been shown to last for 4 h. There have been shown a statistically significant increase of the ROS generation in lymph and a decrease of activities of enzymatic antioxidants in hemocytes of the insects after the implant incorporation. The authors suggest that the key role in maintenance of the oxidation-reduction balance in hemolymph at development of the incapsulation process is played by the lymph non-enzymatic antioxidants. PMID- 20297668 TI - [Phospholipid composition of blood erythrocytes of tundra voles (Microtus oeconomus pall.) inhabiting under different radioecological conditions]. AB - Phospholipid composition has been studied in blood erythrocytes of tundra voles Microtus oeconomus inhabiting territories with normal and increased levels of natural radioactivity at different phases of the populational cycle. It has been shown that rearrangement in the lipid component of blood erythrocyte membranes in tundra voles from radioactively polluted areas are associated with intensification of the lipid peroxidation (LPO) processes and are similar to those observed at the organism natural aging. It has been noted that the capability for peroxide oxidation in erythrocyte lipids is one of the most sensitive stages of the LPO processes to action of the low-intensity radiation in the natural habitat of animals. The change of the populational cycle phases, which is accompanied by hormonal rearrangement in the animal organism, produces an essential effect on the degree of expression of the radiation-induced changes of the studied parameters. PMID- 20297669 TI - [Participation of receptors of the NMDA type in regulation by glutamate of alimentary motor program of the freshwater mollusc lymnaea stagnalis]. AB - A possible participation of receptors of the NMDA type in regulation by glutamate of the Lymnaea stagnalis feeding program was studied in electrophysiological experiments. The specific antagonist of receptors of the N-methyl-D-aspartate (NMDA) type MK-801 has been shown to turn off the endogenous generation of the standard three-phase rhythm or the two-phase rhythm. Stimulation of receptors of this type by their specific agonist, NMDA, on the contrary, increased frequency of the alimentary rhythm and transformed it into the two-phase one. All NMDA effects are eliminated by MK-801. Apart from action on generation of central feeding rhythms, ligands of receptors of the NMDA type changes the tonical level of depolarization and activity of the alimentary circuit motoneurons. MK-801 decreased the initial level of the motoneuron B4 activity and inhibited the excitatory effect both of NMDA and of glutamate itself. There are also obtained data in favor of that earlier reported effect of transformation of the inhibitory response of neurons B4 to glutamate into the excitatory one at action of nitric oxide (NO) donors can be mediated by the specific NO effect on the activity of receptors of the NMDA type. The blocker of NMDA receptors MK-801 has been shown to inhibit the effect of transformation of the response to glutamate. The NO donor nitroprusside enhanced essentially the NMDA excitatory action, while the NO acceptor oral PTIO decreased it. The results obtained with use of ODQ, the blocker of NO-sensitive guanylyl cyclase (GC), allow thinking that effect of NO on activity of the NMDA receptors of the pond snail feeding program can be realized through the metabolic pathway GC--cGMP. On the whole, the obtained results show the pond snail receptors of the NMDA type to participate in generation and rearragement of rhythmical alimentary programs in the tonical excitatory effect on the feeding program motoneurons in the NO-dependent transformation of the glutamate response. PMID- 20297670 TI - [Modulating effect of dopamine on amplitude of GABA-produced chemocontrolled currents in multipolar spinal cord neurons of ammocaete]. AB - By using the patch-clamp method in the whole cell configuration, modulating effect of dopamine on GABA-activated currents has been studied on isolated multipolar spinal cord neurons of the ammocaete (larva of the lamprey Lampetra planeri). At application of dopamine (5 microM), there was observed in some cases a decrease of the GABA-activated current, on average, by 33.3 +/- 8.7 (n = 8, p < 0.01), in other cases--an increase of the amplitude, on average, by 37.3 +/- 11.8% (n = 5, p < 0.01). Concentration of GABA amounted to 2 mM. Study of action of agonists of D1- and D2-receptors on amplitude of che-mocontrolled currents has shown that agonist of D1-receptors (+)-SKF-38393 (5 microM) decreases the GABA activated current amplitude, on average, by 63.1 +/- 11.7% (n = 8, p < 0.01); the agonist of D2-receptors (-)-quinpirole (5 microM) produces in various cells the dopamine-like effects: an increase of the GABA-activated current amplitude, on average, by 61.0 +/- 13.8% (n = 8, p < 0.01) and a decrease of amplitude, on average, by 55.7 +/- 2.0 % (n = 6, p < 0.01). It has been shown that antagonist of D2-receptors sulpiride (5 microM) does not block effects produced by dopamine. The dopamine effects were partially blocked by antagonist of D1-receptors (+)-SCH 23390 (5 microM): a decrease of the GABA-activated amplitude current amounted, on average, to 11.7 +/- 1.8 % (n = 7, p < 0.01), while an increase of amplitude--8.3 +/- 2.0 % (n = 5,p < 0.01). At the same time, effects of agonist of D1-receptors quinpirole (5 microM) were partially blocked by antagonist of D1-receptors (+) SCH-23390: a decrease of the GABA-activated current amplitude amounted, on average, to 9.2 +/- 3.4 % (n = 6, p < 0.01) and an increase of amplitude--6.3 +/- 1.8 % (n = 10, p < 0.01). The obtained data indicate differences of mechanisms of the receptor-mediated effect of agonists of dopamine receptors on GABA-activated and potential-activated currents of multipolar neurons of the ammocaete spinal cord. PMID- 20297671 TI - [Comparison of two kinds of functional asymmetry in the roach Rutilus rutilus (teleostei: cyprinidae)]. AB - In the higher vertebrates, asymmetries of different functions of individual are poorly connected with each other. At present it is unknown whether this poor link is a secondary phenomenon or it is characteristic of different kinds of functional asymmetry already at early stages of vertebrate evolution. In connection with this problem, in the roach Rutilus rutilus we studied asymmetry of two behavioral reactions--movements in an annular corridor and of the C-shaped body bending at a sudden action of electrical stimulus. Different individuals prefer a certain direction of movement in the corridor (to the right or to the left). Comparison of these two kinds of asymmetry in the same individuals has shown the absence of significant association between asymmetries of different reactions. The obtained data indicate that already in the lower vertebrates, different kinds of functional asymmetry are controlled by different mechanisms and are poorly associated with each other. PMID- 20297672 TI - [Effect of neurogenic inactivity on posttetanic responses of rat fast muscle]. AB - At a short-term tetanic stimulation of fast muscle in response to subsequent single stimulation there is recorded a temporary increase of the strength of single contractions that returns to the initial background after 6--10 min. This phenomenon is called posttetanic potentiation (PTP) and is recorded only in fast muscles. The goal of the present work was a study of effect of motor innervation on the course of PTP in rat m. extensor digitorum longus (m. Edl). It has been established that the first signs of effect of motor denervation on the PTP course after section of sciatic nerve in the area of popliteal fossa are recorded as early as at the 4th day after denervation and are expressed in a decrease of strength of single contractions after cessation of tetanic stimulation. These changes reach its maximum at the 14--15th day after denervation when effect of PTP in denervation muscle does not appear at all. Pharmacological analysis of the studied phenomenon has shown that dantrolene (10 microM) suppresses amplitude of the single contraction, but does not prevent the appearance of PTP in intact muscle. In the denervation of m. Edl, instead of the appearance of PTP, after a brief slight increase, a gradual decrease of the strength of contraction is recorded. Thus, it can be concluded that no significant PTP changes are present under action of dantrolene. It has been established that after the 10-min muscle incubation in Ringer's solution with caffeine (4 mM), strength of the single contraction in intact and denervated muscles increases by approximately equal value. Tetanization of intact muscle increases strength of the single contraction approximately by 7 % more than this occurs after incubation with caffeine, i. e., this substance reduces the capability of muscle for the appearance of PTP. On denervation muscle, caffeine increases strength of singly contraction, but does not potentiate development of PTP. The obtained data allow concluding about the existence of different mechanisms underlying the pretetatnic contraction and posttetanic potentiation of the single contraction. The main difference between two types of contractions can be recruiting of additional DICR-channels in the process of contraction under conditions of PTP. PMID- 20297673 TI - [The structural organization of binding determinants in insulin-like growth factor-I (IGF-I) molecule]. AB - Insulin-like growth factor I (IGF-I) is a peptide related to insulin and IGF-II. These three related peptides produce similar biological effects, but each of them has its irreplaceable physiological significance in the organism. Multisided functional role of IGF-I in the organisms is due to its unique binding properties. Specifically, but with different degree of affinity, it is able to interact with three receptors (IGF-l-receptor, insulin receptor, and IGF-2 receptor) and six binding proteins (IGFBP 1-6). To interact with each of the above objects, the 1GF-I molecule contains individual structural determinants- binding domains (BD) providing strict specificity of interaction with them. Responsible for the IGF-I biological effects and binding with IGF-l-receptor is alpha-domain, for binding with insulin receptor--beta-, IGF-2--gamma-, while with all BP--delta-BD, respectively. Results of experimental study of binding domains are not a always can be estimated unanimously. The proposed by the author system of criteria for evaluation of changes in affinity of the IGF-I analogies proposed by the author allows unraveling the structural organization of each of the domains and tracing dependence on it of the peptide affinity to the particular object. This work considers composition, organization, and principle of formation of affinity of there binding IGF-I domains (alpha-, gamma-, and delta-BD). The alpha-domain includes three tyrosines from three different molecule sites (B-24, C-3 1, and A-60) disposed spatially in the direct vicinity on its one surface. The delta-domain also is considered as the domain participating in the high affinity interaction; by composition and location in molecule it principally differs from alpha-BD, with the structural organization that so far has not been decoded. Analyzed in detail is the key significance of the N-terminal site of the B-chain--the linear site of the domain--for binding of IGF-I with BP, functional heterogeneity of its constituent residues, and the characteristic principle of formation of affinity to BP. Analysis indicates a probability of the second site of delta-BD, quite possibly not the only one, and a high sensitivity of the domain to configuration of the IGF-I molecule surface. Structural organization and peculiarities of affinity formation in the gamma-domain argammae studied the best in three related peptides; it consists of two linearly exposed sites of A chain. Composition of the site S-1 A (Phe8, Arg9, Serl 0) provides a possibility of binding the ligand with IGF-I-receptor, while the level ofaf-finity to it depends on the composition of S-2. The S-2 composition A (Arg14, Arg15) determines the low affinity of IGF-I to the IGF-2-receptor. The clear functioning of IGF-I and elimination of mixture of functions at the level of the binding activity depend on the spatial autonomy of different nature BD, difference in structural organization of each of the domains, and a peculiarity of principles affinity in each formation case. The spatial coordination of several BD sites is the condition for transmission of the "structural sig-nal" by regulatory peptide. The performed analysis provides the direct notion of dependence of the binding ability of the IGF-I molecule that has BD of different nature on their structural peculiarities and allows using the revealed regularities at searching for BD in the newly discovered insulin-like peptides. PMID- 20297674 TI - [Autoimmune processes after long-term low-level exposure to electromagnetic fields (the results of an experiment). Part 1. Mobile communications and changes in electromagnetic conditions for the population. Needs for additional substantiation of the existing hygienic standards]. AB - Mobile communications provides a new source of electromagnetic exposure for almost the whole population of the Russian Federation. For the first time in the history of civilization the brain of mobile phone users was exposed to localized radiofrequency (RF) electromagnetic fields (EMF). Population exposure from the base stations is also considered to be specific. However, existing standards for limiting the exposure do not account for this special EMF source and may not ensure the absence of health effects. There was a need for reliable information that would extend databases used for development of new standards. As recommended by the World Health Organization an additional experiment was performed under the supervision of foreign experts, which showed changes in autoimmune status in rats after long-term low-level RF EMF exposure with an incident power density of 500 microW/cm2. PMID- 20297675 TI - [Autoimmune processes after long-term low-level exposure to electromagnetic fields (the results of an experiment). Part 2. General scheme and conditions of the experiment. Development of RF exposure conditions complying with experimental tasks. Animal's status during the long-term exposure]. AB - This paper describes the conditions for handling and exposure of experimental animals (Wistar rats) and methods used in the study of immunological effects of long-term low-level (500 microW/cm2) exposure to radiofrequency (2450 MHz) electromagnetic fields, performed under auspices of the World Health Organization. PMID- 20297677 TI - [Autoimmune processes after long-term low-level exposure to electromagnetic fields (the results of an experiment). Part 4. Manifestation of oxidative intracellular stress-reaction after long-term non-thermal EMF exposure of rats]. AB - This paper presents the results of the study of the effects of long-term low level exposure of rats to microwaves. Rats were exposed in far field to 2450 MHz continuous wave fields providing an incident power density at the cages of 500 microW/cm2 for 7 hours daily for a total of 30 days resulting in a whole-body SAR of 0.16 +/- 0.04 W/kg. Three groups ("EMF-exposure", "sham-exposure" and cage control) were formed, each consisting of 16 rats. Circulating antibodies (IgA, IgG and IgM) directed against 16 chemical substances were evaluated in coded serum from each group of rats by enzyme multiplied analysis (ELISA test). An increased amount of compounds resulting from interaction of amino acids with nitric oxide (NO) or its derivatives (NO2-Tyrosine, NO-Arginine, NO-Cysteine + NO Bovine Serum Albumin, NJ-Methionine + NO-Asparagine + No-Histidine, NO-BTrypnohan + NJ-Tyrosin), fatty acids with small chains, hydroxylated fatty acids, palmitic/myristic/oleic acid, AZE (product of oxidation of fatty acids) was found in blood serum from EMF-exposed rats. As a rule, antibodies to conjugated antigens were seen for IgM, rarely seen for IgG and were completely absent for IgA. The levels of antibodies were higher on day 7 after the exposure compared to those on day 14 after the exposure. PMID- 20297676 TI - [Autoimmune processes after long-term low-level exposure to electromagnetic fields (the results of an experiment). Part 3. The effect of the long-term non thermal RF EMF exposure on complement-fixation antibodies against homologenous tissue]. AB - This paper presents the results of the study of immunological effects of long term low-level exposure of rats to microwaves. Rats were exposed in the far field to 2450 MHz continuous wave fields providing an incident power density at the cages of 500 microW/cm2 for 7 hours daily for a total of 30 days, resulting in a whole-body SAR of 0.16 +/- 0.04 W/kg. Effects of the exposure on immunological parameters in the brain and liver of rats were studied using Complement Fixation Test at low temperature (4 degrees C). Three groups ("EMF-exposure", "sham exposure" and cage-control) were formed, each consisting of 16 rats. On the 14th day after the 30-day exposure, titers of antibodies against brain tissue were 0.69 +/- 0.08 in the cage-control group, 0.89 +/- 0.05 in the sham-exposed group and 1.19 +/- 0.07 in the EMF-exposed group. The appearance of antibodies against liver antigens was less. The increase in titres of antibodies against brain homogenates in the sham-exposed and EMF-exposed groups could be explained by the stress-reaction of the animals and autoimmunization of organism. PMID- 20297678 TI - [Autoimmune processes after long-term low-level exposure to electromagnetic fields (the results of an experiment). Part 5. Impact of the blood serum from rats exposed to low-level electromagnetic fields on pregnancy, foetus and offspring development of intact female rats]. AB - This study evaluated possible adverse effects of injection of blood serum from rats exposed to microwaves at a power density of 500 microW/cm2 on pregnancy and foetal and offspring development in intact female rats. The study was performed with 59 pregnant Wistar rats. In utero mortality, embryo and foetal body weights and placenta weight were used for the evaluation of embryo and foetal development. Generally accepted integral and specific parameters were used for the evaluation of postnatal development of offspring during the first 30 days of life. It was shown that intra peritoneal injection of blood serum from IMF exposed rats (chronic 30-day RF exposure at 500 microW/cm2) to intact rats on the 10th day of pregnancy resulted in adverse effects on foetal and offspring development. Total mortality (in utero + postnatal) as well as delay in offspring development was higher in this group. PMID- 20297679 TI - [Multidrug resistance increase of tumor cells at the effect of radiation and phorbol ether depends on protein kinase C and reactive oxygen species]. AB - The effects of phorbol ether (PMA) and ionizing radiation on multidrug resistance (MDR) of human larynx cancer cells HEp-2 and the dependences of these effects on protein kinase C (PKC) activity and reactive oxygen species (ROS) production were studied. MDR was determined by transport rate of rhodamine 123 off cells and production of ROS in cells was measured by means of 2'7' dichlorodigidrofuorescein oxidation to fluorescent 2',7'-dichlorofluorescein. ROS production was increased in cells at PMA treatment. This increase was caused by PKC dependent activation of NADPH-oxidase because the ROS increase suppressed completely with PKC and oxidase inhibitors. It was shown that tumor cell MDR was increased 16 h after PMA (100 nM) and radiation (1 Gy) treatment. The MDR increase depends on PKC activity and ROS increase in cells at both influences since PKC inhibitor and antioxidant, lipoic acid suppressed MDR increase. The obtained data are in accordance with hypothesis about the necessity of activation both signalization and stress reaction for initiation of transcription of transport protein genes which responsible for MDR of tumor cells. PMID- 20297680 TI - [Bystander effect development in human mesenchymal stem cells after exposure to adaptive dose of X-radiation]. AB - Transposition and mutual approaching of pericentromeric loci 1q12 of homological chromosomes from the nuclear membrane towards the nuclear centre as well as activation of the chromosomal nucleolus-forming regions (NFR) are observed in human mesenchymal stem cells (hMSCs) as an initial stages of the adaptive response (AR) after exposure to low doses of X-radiation (10 cGy). All these reactions are also induced after addition of cultivation medium from irradiated cells to intact bystander-cells and this phenomenon called bystander effect (BE). Recently the same AR and BE induction results were obtained for human G0 lymphocytes. All these data indicate the existence of universal reaction of homological chromosome loci transposition which was revealed during AR development in differentiated (lymphocytes) and non-differentiated (hMSCs) and also it shows possibility of radiational BE development in suspension and monolayer cell cultures upon addition of stress-signalization factors in incubation medium. We suppose that these factors are extracellular genome DNA fragments apoptotic cells. PMID- 20297681 TI - [Antiradiation effects of vaccine Grippol]. AB - The propose of these examination was the study of antiradiation effects of vaccine Grippol (VG). It was determined, that subcutaneous injection VG mice (0.2 ml), hamsters (0.2 ml), dogs (0.5 ml) before 1-14 days of total gamma-irradiation (2.5-8.5 Gy) had positive effect of acute radiation disease. This effect was expressed in increase of survival the mice and hamsters on 30-60%, increase number cells in bone marrow and neutrophiles, erythrocytes, lymphocytes and hemoglobin in blood by comparison with control mice. VG stimulated increase of contents of leucocytes in blood of irradiated (2.5 Gy) dogs. PMID- 20297682 TI - [Impact of the antioxidant Phenozan and low dose radiation on the level of p53 and BCL-2 proteins of mice different lines]. AB - The influence of the antioxidant Phenozan and 1.2 cGy gamma-radiation on the level of apoptotic proteins was determined for normal mice of F1 (CBA x C57BL) and leucosis AKR mice that are more sensitive to the irradiation. The constitutional level of p53 proteins in serum leucosis AKR mice was higher, than those in F1 (CBA x C57BL) mice, possible from accumulation of mutant p53 protein and viral infection of AKR mice. It was determined that injection of Phenozan in 10(-14) mol/kg and in 10(-4) mol/kg led to rising a p53 protein and bcl-2 protein level in serum and spleen in these line of mice, and lowering the number of double-strand breaks DNA spleen shown earlier. Common action Phenozan and 1.2 cGy gamma-radiation led to higher rising of p53 protein level than Phenozan only in F1 (CBA x C57BL) mice, stimulate possibly different pathway of p53 regulation. We assume that Phenozan can activate the reparation processes but not the processes of apoptosis in the cell and has a radioprotective properties. PMID- 20297683 TI - [Iodide metabolism in the rat thyroid at early and remote periods following the long-term exposure of external fractionated gamma-radiation]. AB - The research was made into the effects of 20-fold exposure to external gamma radiation (0.1-0.5 Gy) on the activities of the key steps of iodide metabolism (absorption, oxidation and organification) in the rat thyroid as well as on its morphologic structure at the early (1 day) and remote (30 and 180 days) periods after the radiation. A wave-like pattern of changes in the thyroid function was found at the postradiation period. It was shown that after 1 day following the radiation the thyroids demonstrated elevated concentrations of total (by 30.1 54.4%), protein-bound (by 24.4-37.4%) and free (by 32.1-60.8%) iodide which were decreased to the control values after 30 days following the radiation. At more remote periods (180 days) thyroids of two (0.25 and 0.5 Gy) groups had 24.5 and 34.8%-diminished thyroperoxidase activity and 12.7 to 25.5%-reduced iodide concentrations, which indicates disturbed iodide absorption and oxidation along with thyroid hypertrophy. The decreased thyroid functional activity is characterized by development of focal perivascular sclerosis, desquamation of follicular epithelium with vacuolisation as well as follicular structure destruction. The mechanisms of postradiation changes in thyroid metabolism and their role in adaptation and disturbances in thyrocyte function are discussed. PMID- 20297684 TI - [Attractive and immunosuppressive properties of volatile secretions induced in mice separately and combine influence of ionizing radiation and cyclophosphamide]. AB - We have studied the properties of volatile secretions induced in laboratory mice, separately or combined influence of ionizing radiation and cyclophosphamide. The reaction of preference-avoidance response in the T-maze revealed that the urine samples of mice in the early period after exposure to ionizing radiation in doses of 2 and 4 Gy contain attractive for intact animals volatile components. While the introduction of cyclophosphamide in doses of 20 or 35 mg/g provokes the secretion of volatile components of aversive, repealing properties towards of intact individuals. Combined exposure to these factors leads to a reciprocal compensation of the impact of volatile secretions in the preference-avoidance response of intact mice. The examined effects depend to some extent on the dose of radiation and cyclophosphamide. Induced both by separate and associated exposure to radiation and cyclophosphamide volatile allocation have depressing effect of the humoral immune response, regardless of whether they are attractive or aversive properties. We are discussing their role in the mechanisms of chemosignaling. PMID- 20297685 TI - The consideration of biological effectiveness of low energy protons using biophysical modeling of the effects induced by exposure of V79 cells. AB - We have applied Monte Carlo track structure simulations to estimate relative biological effectiveness (RBE) of low-energy protons using biophysical modelling of radiation effects induced by exposure of V79 cells growing in mono-layer. The microscopic energy deposition in cell nucleus and sub-nucleus volumes was investigated in order to understand the reasons of enhanced biological effectiveness near Bragg peak. Theoretical estimations of RBE based on frequency/dose average lineal energy and calculated yields of initial DNA breaks were collated with experimental RBE(M) data. It was found: 1) dose average lineal energy for whole cell nucleus as a function of proton energy shows a distinct peak at 550 keV; 2) the peak values for sub-nucleus volumes are large compared with the whole cell nucleus; 3) the yield of complex DNA breaks correlates with experimental RBE(M) data. PMID- 20297686 TI - [90Sr in residents of the Iset riverside settlements]. AB - The river Iset belongs to the Techa-Iset-Tobol-Irtysh-Ob system contaminated by liquid radioactive wastes from Mayak plutonium facility in 1949-1956. This study represents the first retrospective analysis of postmortem measurements of 90Sr in bones from residents of the Iset riverside settlements in 1960-1982. It was shown that 90Sr concentration in bones of residents lived in settlements located downstream from the Techa river mouth (Shadrinsk, Isetskoye, Yalutorovsk) was 5 times higher than average 90Sr concentration in bones of the Russian residents. There was not statistically significant difference in accumulated 90Sr in bones between residents of the considered Iset' settlements indicating similar levels of 90Sr ingestion. Dietary 90Sr intake was reconstructed from the measurements of the radionuclide in bones. Total 90Sr dietary intake in 1950-1975 was 68 kBq; and 90% of the intake occurred in 1950-1961. In 1960s, 90Sr-contamination of the diet in settlements located downstream from the Techa river mouth was mostly (by 70%) due to global fallouts. Absorbed dose in the red bone marrow cumulated over 25 years of exposure was equal to 14 (4.7-42) mGy. PMID- 20297687 TI - [Carbon stable isotope composition (delta 13C) of lichen thalli in the forests in the vicinity of the Chernobyl atomic power station]. AB - The stable isotope abundance of carbon in the lichens Cladina mitis, Cladonia crispata Hypogymnia physodes, Parmelia sulcata has been investigated in a study relating these values with known levels of 106Ru, 134Cs, 137Cs and 144Ce defined activity in their thalli in the pine forests of region within a 30-km radius of the Chernobyl atomic power station and beyond it (37 km). All 63 samples of the lichens were obtained from 7 different sites. Small effects on delta 13C values in the lichens Cladina mitis, Hypogymnia physodes were found to be associated with distance from CNPP, activity level of radionuclides in them thalli whereas at Cladonia crispata is observed weighting of carbon with increase in values of 134Cs and 137Cs activity in thalli. Values of delta 13C the investigated lichen species more depends on habitat conditions rather than from levels of thalli radioactivity. In our study we didn't reveal the isotope specificity of any one species as it was not possible to establish a correlation between values of delta 13C and a particular species. PMID- 20297688 TI - [Speech recognition in the norm and pathology]. AB - The purpose of this paper was to study theoretically and experimentally clinical and electrophysiological correlates of the human abilities to recognize emotions in speech. It was shown that the disorder of the recognition of emotions in speech occurred following the lesion of the right temporal region, however the most serious defect of recognition manifested itself at the frontal temporal localization of the lesion. The comparison of the EEG characteristics between two groups of subjects with high and low indices of recognition of emotions in speech revealed a higher level of activation in the posterior temporal regions of the right hemisphere and in the frontal regions of the left hemisphere in the group with the low index of recognition. Clinical data and findings obtained in electrophysiological studies permitted us to make a conclusion that the recognition of emotions in speech involved not only temporal regions of the right hemisphere, but also speech centers in the left hemisphere. PMID- 20297689 TI - [Weak irregular periodical winces of rats in slow wave sleep (SWS) coupled to the cerebral cortex activation and local falls in the cortex redox potential (E)]. AB - The current study has been fulfilled to advance our pioneer studies of the brain energy metabolism (EM) in animals [Shvets-Teneta-Gurii T. B., 1979: Shvets-Teneta Gurii T. B., 1986; Shvets-Teneta-Gurii T. B., 1986 et al., 2002]. The gist of this line consists of the simultaneous multipoint measuring local changes in the cerebral cortex redox potential (the E) in animals. Polygraphic recordings of the the E, electrocorticogram (ECoG) and general motor activity were made in sleep wakefulness cycles of rats. It has been found that transition of rats to slow wave sleep (SWS) was accompanied by the E lowering in the metabolic active sites and by arising compound oscillations in the E. At the same time, irregular periodic weak winces (3-40-sec apart) appeared and were accompanied by the ECoG activation and by the E decrease. There are data that episodes of the ECoG activation in SWS are accompanied by pO2 drops in the brain structures [Sarkisova K. Yu., Kolomeitseva I. A., 1900]. Visual and acoustic stimulation being presented in human slow-wave sleep brings down the brain oxygenation level [Born A. P. et al., 2002; Czisch M. et al., 2002]. In sum, the given facts indicate an increase in the activity of functional units in SWS that are fueled by glycolytic compartment. Recently published data suggest that the astroglia is the major compartment of aerobic glycolysis [Dienel G. A., Cruz N. F., 2006; Magistretti P. J., 2006]. It can be speculated that astroglia plays the especially important part in events taking place during SWS. PMID- 20297690 TI - [Role of erythropoietin in the ischemic preconditioning. Postconditioning and regeneration of brain after ischemia]. AB - Analysis of published data indicates that erythropoietin plays an important role in regulation of brain tolerance to impact of ischemia-reperfusion. This cytokine is involved in ischemic preconditioning of the brain and can mimic the phenomenon of preconditioning and postconditioning. However, it is unclear whether endogenous erythropoietin takes part in postconditioning of the brain. It is established that erythropoietin inhibits apoptosis of neurons after ischemia reperfusion. It was found that erythropoietin could stimulate regeneration of the brain after ischemia. Signaling mechanism of neuroprotective action of erythropoietin is well studied but there are very little data on the mechanism of erythropoietin-induced neurogenesis and neoangiogenesis. It is unknown whether erythropoietin can exhibit infarct-limiting effect in humans and stimulate neurogenesis and neoangiogenesis in patients after insult. PMID- 20297691 TI - [Erythropoietin influence on oxygen transport function of blood and prooxidant/antioxidant balance in rabbits under lipopolysaccharide injection]. AB - We aimed to study the erythropoietin influence on oxygen transport function of blood and prooxidant/antioxidant balance in rabbits under lipopolysaccharide injection. Recombinant human erythropoietin-alpha was administered intraperitoneally in the dose 1000 U/kg 30 minutes before intravenous injection of 500 mkg/kg lipopolysaccharide from E. coli. After 12 hours, blood samples were collected for the assessment of oxygen transport function of blood; nitrate/nitrite levels and tissue samples were collected for measurement of conjugated dienes, malondialdehyde, alpha-tocopherol and catalase. Erythropoietin improves parameters of oxygen transport function of blood, increases hemoglobin oxygen affinity through the NO-dependent mechanism, reduces activity of free radical processes, and increases antioxidant protection under lipopolysaccharide injection. PMID- 20297692 TI - [Heterogeneity of the mechanisms of damaging nervous cells in demyelinating autoimmune diseases of the CNS]. AB - A review of modern state of the neurodegeneration problem in demyelinating autoimmune diseases. Experimental and clinical proofs of heterogeneity of the mechanisms of destruction of the nervous tissue are given. Interconnection among the processes of neuroinflammation, excitotoxicity and oxidative stress are considered under damage of oligodendrocytes (myelin) and neurons (axons). PMID- 20297693 TI - [The impact of early developmental impairment of the receptor-dependent glucocorticoid action on the pituitary adrenal axis activity and behavior of male rats]. AB - The effects of administration of cortisol or glucocorticoid receptor antagonist RU 38486 to male rats from days 1 to 5 of postnatal life on the stress reactivity of the pituitary-adrenocortical axis, open field behavior, and anxiety in an elevated-plus maze were studied. Neonatal cortisol administration induced increase in locomotor and rearing activity as well as anxiety level in 30-day-old male rats, but the pituitary-adrenocortical axis activity and behavior of adult animals was unaltered. Whereas the impairment of the receptor-dependent glucocorticoid action in neonatal brain resulted in longer-lasting hormonal stress responses, reduction number of locomotion, and increase the anxiety level in adulthood. These data suggest that changes of glucocorticoid receptors in the brain during the neonatal period of devlopment can lead to different hormonal and behavioral impairments in adult male rats. PMID- 20297694 TI - [Oxidative modification of rat blood proteins after destruction capsaicin sensitive nerve and change of nitric oxide level]. AB - Content of blood protein carbonyl derivates in rats are determined to assess oxidative modification of protein after destruction of capsaicin-sensitive nerve and change of nitric oxide (NO) level. Deafferentation of these nerves produces increase of the protein carbonyl derivates content. The increase of NO by L arginine does not affect protein oxidative destruction produced by ablation of capsaicin-sensitive nerve. Selective inhibitor of neuronal synthase NO (n-NOS) 7 nitroindazole (7-NI) results in similar effect. L-NAME increased oxidative destruction of proteins. These results demonstrate that deafferentation of capsaicin-sensitive nerve induces oxidative destruction of proteins. NO has party to mediating oxidative modification of proteins. PMID- 20297695 TI - [Osmoregulating effect of vasopressin with prolonged action on Brattleboro rats with hypothalamic diabetes insipidus]. AB - The particularities of urine osmotic concentration depending on hormonal background of vasopressin were studied in rats. It was found that WAG and Brattleboro lines of rats characterized respectively by normal level and absence of endogenous vasopressin, possess interline correlation of urine osmolality (p = 0.86) in various conditions between the extreme hydrating and dehydratation. Concentrating level of WAG rats varies from 747 +/- 94 to 2936 +/- 128 mOsm/kg, but that of Brattleboro rats changes more within the 160 +/- 9 being twice lower as isotonicity to 1305 +/- 142 mOcm/kg. Urine concentrating goes up to 1391 +/- 76 mOcm/kg in Brattleboro rats already on the day of the action of exogenous vasopressin secreted from ALZET minipump, however, in spite of constant work of this minipump during 4 hrs a week, further increasing of urine osmolality was not observed in Brattleboro rats. PMID- 20297696 TI - [Influence of permafrost microorganisms on the quality and duration of life of laboratory animals]. AB - Microorganisms of genus Bacillus strain 3M (permafrost microorganisms--PM), allocated from the samples of permafrost soils from Mamontova Mountain (Yakutia) are influenced by the quality and duration of life of elderly mice. PMs were injected intraperitoneally to CBA mice at the age of 17 months. Motion activity, muscular force (lifting of cargo test), food instinct activity (dosed starvation test) and cellular immunity activity (reaction of delayed-type hypersensitivity in vivo) of animals have increased, and psychoemotional condition of animals has improved under influence of PM. Average duration of life has increased by 9.19%, minimal duration of life--by 41.93%, maximal duration of life--by 7.68%. Duration of survival (the remaining life after injection of microorganisms) has increased more significantly: minimal--by 141.9%, on the average--by 28.0%, maximal--by 20.4%. Mechanisms of PM influence on increase of laboratory mice duration of life up to the top specific limit through the positive influence on quality of their life are discussed. PMID- 20297697 TI - AIDS in children--epidemiology, clinical course, oral manifestations and management. AB - HIV/AIDS has gained enormous proportion globally. In 2007, there were an estimated 33 million people living with HIV and an estimated 270,000 HIV infected children younger than 15 years died because of AIDS, HIV/AIDS can manifest in different forms and in present day scenario, it is imperative that dentists know its clinical presentation and management. Oral manifestations are one of the earliest indicators of HIV infection and progression in children, as in adults, although the specific manifestations differ between adults and children. The aim of this paper is to briefly review, on the basis of literature, the AIDS epidemiology, transmission, clinical course, oral manifestations and their management in children. PMID- 20297698 TI - Obesity in children: a challenge that pediatric dentistry should not ignore- review of the literature. AB - The link between childhood oral diseases and obesity is demonstrated by their increasing prevalence, potential cause and effect relationship, the significant deleterious effect on the child's present and future oral and systemic health, and the influence of obesity on conscious sedation. The purpose of this manuscript is to review the literature on the relationships between childhood oral diseases and obesity, and between obesity, breathing and conscious sedation. While some reports suggest a connection between caries and obesity others do not, and it is unclear if they correlate or they just coexist since they have common etiologic and/or facilitating factors. Deleterious effects of dental caries and obesity on the systemic condition are clear, may potentiate each other, and facilitate the development and progress of chronic or acute systemic conditions. Obesity may interfere with the possibility to sedate patients because of potential breathing problems, or modify the effect of the sedative agents. Health providers should be aware of the increasing challenge posed by the correlations between dental caries, obesity, oral and systemic diseases. Furthermore, pediatric dentistry should team with other health professions in order to cooperate in the prevention and treatment of these diseases. PMID- 20297699 TI - Autotransplantation of an intruded lateral incisor replacing an avulsed central incisor--a case report. AB - Oral injuries cause aesthetic, psychological, social, and therapeutic problems and also affect a large number of people, causing irreparable dental loss not only at the accident time but also during post-treatment. Missing permanent teeth by trauma in children is a particular challenge, especially in the anterior region of the maxilla. In the past few decades, tooth transplantation has been successfully researched for the treatment of anterior tooth loss in young individuals. OBJECTIVE: The present case describes transplantation of an excessive intrusive maxillary left lateral incisor into the socket of avulsed maxillary left central incisor STUDY DESIGN: The lateral incisor tooth was extracted and placed into the socket of avulsed tooth. Splinting was maintained for 2 weeks. After the root canal treatment, the crown of the lateral incisor tooth was reshaped with composite resin in central tooth form and performed an interim prosthesis both preventing movement of the canine tooth into the space of the transplanted lateral incisor tooth and providing aesthetic. CONCLUSION: The treatment provided is considered to be an interim solution for space maintenance, with time the child patient may reach an age that allows alternative, more definitive treatment as implant. PMID- 20297700 TI - Bilateral bimaxillary bi-rooted primary canines: report of a case. AB - Bilateral bi-rooted primary canines are a rare dental anomaly and the occurrence with a syndrome is even rarer. This dental anomaly has mostly occurred in African populations. This article reports a case of bi-rooted primary canines bilaterally located in both jaws of a 15-year-old Chinese boy who also suffered from cleidocranial dysostosis (CCD). PMID- 20297701 TI - Clinical evaluation of Papacarie in primary teeth. AB - The change in the concepts of cavity preparation and the development of reliable adhesive materials lead to the development of alternative methods of caries removal. Chemo-mechanical caries removal (CMCR) involves the chemical softening of carious dentin, followed by its removal with gentle excavation. OBJECTIVE: The present study was conducted to evaluate clinically the efficiency of caries removal using a new chemo-mechanical agent (Papacarie) compared to the conventional drilling method including the need for local anesthesia, the need for drill, duration of the treatment and the pain reaction. STUDY DESIGN: This study was split mouth design. The study was performed on thirty seven bilateral open carious lesions. They were divided into two equal groups according to method of caries removal. In Group I, caries was removed using the Papacarie system and in Group II, caries was removed with the conventional drill. RESULTS: The results showed that the Papacarie was as efficient as the drill in caries removal from open carious lesions with no significant difference in the operating time. The new CMCR agent also reduced significantly the need for local anesthesia and the use of drill. In addition, Papacarie was also more comfortable than the traditional rotatory instruments. CONCLUSIONS: It was concluded that Papacarie could be an effective caries removal method to treat children, particularly those who present with early childhood caries or management problems. PMID- 20297702 TI - Leaching of ions from materials used in alternative restorative technique under neutral and acidic conditions: a comparative evaluation. AB - This study was undertaken to gain an insight into the interaction of conventional glass ionomers (GC Fuji II, GC Fuji IX GP and Chem Flex restorative materials) commonly used in Alternative Restorative Technique (ART) with aqueous solutions in terms of water sorption, solution buffering and ion release. Both immature and mature specimens of all materials evaluated, showed a substantial increase in mass, pH and release of Na, Ca, Sr, Al, Si, P and F following immersion in deionized water lactic acid (pH 2.7) and lactic acid (pH 5.2). However the ion release profiles were found to be greater in acidic media (Lactic Acid pH 2.7 > Lactic Acid pH 5.2) than in deionized water. PMID- 20297703 TI - Effect of glass ionomer cement and fluoride varnish on the remineralization of artificial proximal caries in situ. AB - OBJECTIVE: To compare the effect of glass ionomer cement (GIC) and fluoride varnish (F-varnish) on artificial proximal caries in situ. STUDY DESIGN: Two 1 x 3 mm2 enamel slabs, divided into three 1 x 1 mm2 windows, were prepared from each proximal surface of 18 premolars. Each slab was distributed into a control area, an intact enamel area and a test area. Artificial lesions were created on the control and test areas by immersing in demineralizing solution for 24 hours. The test windows were either applied with GIC or F-varnish and the full slabs inserted into orthodontic brackets as carriers, which were then bonded to the buccal surfaces of the 6 upper posterior teeth of 6 volunteers using non-fluoride dentifrice for 30 days. There was a 1-week washout period in this crossover study. The middle specimens of the three windows were cross-sectioned to analyze the carious lesion area by a polarized light microscope and calculated with Image Pro plus software. RESULTS: The average carious lesion area under GIC was significantly less than that under F-varnish (p < 0.05). CONCLUSION: GIC promotes more remineralization of artificial carious lesions on proximal surfaces than F varnish. PMID- 20297704 TI - Maternal-child oral health behaviors and caries experience in the child. AB - OBJECTIVE: This study examined maternal and child oral health behaviors and potential risk factors for dental caries in high-risk children. STUDY DESIGN: Data on oral health practices were collected from surveys of mother/caregivers and the child's dental chart was reviewed. Linear regression and ordered probit regression models were used to examine data. RESULTS: A total of sixty questionnaires were completed. There was a marginally significant relationship (P = .08) between number of times per day a child consumed a sweetened beverage and the dmfs of the child. Mothers who snacked more frequently had a greater probability (24%) that their child snacked 3 times or more. Mothers who drank a sweetened beverage more frequently had a greater probability (40%) that their child drank a sweetened beverage 3 or more times a day. Mothers who brushed their teeth with fluoridated toothpaste had a greater probability (79%) that their child brushed 2 or more times a day with fluoridated toothpaste. CONCLUSIONS: Two maternal variables, reported soft drink consumption and dietary habits, appear promising for caries prediction. Implementation of dietary counseling and oral health programs for mothers and research merit further exploration. PMID- 20297705 TI - Parents' attitude toward their children's appearance in the case of esthetic defects of the anterior primary teeth. AB - PURPOSE: To evaluate parents' attitude toward esthetic defects of maxillary primary incisors and the association between various demographic parameters and the treatment parents chose for their children. METHODS: The study consisted of two parts: 1) a clinical examination of the child's primary incisors, and 2) a questionnaire for the accompanying parent. 362 parents who accompanied 294 children aged 1-6 years, participated in the study. They were divided in 2 groups: parents' accompanying children with esthetic defects (study group) and parents' of children without esthetic defects (control group). RESULTS: Significantly more parents in the study group (73%) recognized an esthetic problem in their child's incisors, compared to (17%) in the control group. Eighty seven percent (219 in the Study Group [85.20%] and 97 in the Control Group [92.4%]) advocated dental treatment to save a primary tooth even if the chances for success were only 50%. 35.9% rejected the idea of a prosthetic replacement for a lost primary incisor. The same percentage of parents (35.9%) answered that they "want it 'very much'" while the rest (28.2%) chose intermediate scores '2-3' on a scale of '0' (= not at all) to '5' (= yes! very much). CONCLUSION: Parents are interested in a conservative treatment for preserving esthetically damaged incisors, but will be less enthusiastic to replace extracted or missing teeth with an esthetic device. PMID- 20297706 TI - The effects of children's drinks on the color stability of various restorative materials. AB - OBJECTIVE: To evaluate the effects of exposure to various children's drinks on the color stability of different esthetic restorative material commonly used in pediatric dentistry. STUDY DESIGN: Cylindrical specimens (15 x 2mm) were prepared from four different restorative materials (Fuji IX, Fuji II LC, Dyract Extra, and Filtek Z250). For each material, 20 specimens were prepared and divided into four groups. Each group was stored in a different solution (distilled water chocolate milk, cola, grape juice) for 24 hours. A colorimeter was used to measure the color of each specimen both before and after staining. Color change (deltaE*) was calculated, and data was analyzed using two-way ANOVA and Tukey HSD tests. RESULTS: For all restorative materials, the lowest deltaE* values were recorded for specimens stored in distilled water (0.42), followed by chocolate milk (0.88), grape juice (3.45) and cola (3.97). Among the four restorative materials tested, Fuji II LC showed the most color change (3.71) and Fuji IX the least (1.33). There were statistically significant differences among above groups (p < 0.05). CONCLUSIONS: DeltaE* values were acceptable for all materials tested, with the exception of Fuji II LC. Therefore, the use of RMGIC should be avoided in anterior restorations in children due to esthetic reasons. PMID- 20297707 TI - Self-report of pain in children treated according to the atraumatic restorative treatment and the conventional restorative treatment--a pilot study. AB - OBJECTIVE: To compare the level of pain among children treated according to the Atraumatic Restorative Treatment (ART) and the Conventional Restorative Treatment (CRT). STUDY DESIGN: Forty children of both genders, 4- to 7-years old, presenting Class I cavitated dentin lesions in primary molars were randomly allocated to 2 groups. One group (CRT) received conventional restorative treatment using rotary instruments, while in the other one (ART) hand instruments were used to perform the restorations. All children were treated by the same operator A high-viscosity glass-ionomer cement (Fuji IX) was used to restore the teeth in both groups. Children's pain was measured at the end of the first restorative treatment session using the Wong-Baker FACES Pain Rating Scale (dependent variable). Age, gender, treatment time and treatment group were independent variables. ANOVA and ANCOVA tests were used to analyze the data. RESULTS: The CRT procedure took longer than the ART procedure (p < 0.001). Children from the ART group reported less pain than those from the CRT group (p = 0.0037). Four year olds reported more pain than 5- to 7-year olds (p < 0.0001) in both groups. CONCLUSIONS: Restorations placed using ART were less time consuming, children felt less pain when the ART approach was used, and younger children (4 years) reported more pain than the older ones for both restorative treatments. PMID- 20297708 TI - Microleakage of different temporary filling materials in primary teeth. AB - OBJECTIVE: The aim of this study was to compare the sealing properties of IRM, Coltosol, Cavit G, Adhesor and Clip, which used as temporary filling material in coronal access openings in extracted human primary teeth. STUDY DESIGN: Standardized access cavities of 2 x 2 mm were prepared in the eighty-four, caries free human primary anterior teeth. The teeth were divided randomly into five groups of 16 teeth each. Temporary restorative materials Group A: IRM (Dentsply), Group B: Coltosol (Coltone), Group C: Cavit G (3M), Group D: Adhesor (Spofa Dental) and Group E: Clip (Voco) were applied according to the manufacturer's directions. The specimens were immersed silver nitrate and placed in film developer under fluorescent for 24 hours. The sectioned specimens were evaluated under a digital microscope at x 20 magnifications and blindly scored for microleakage. RESULTS: Clip presented the least microleakage value whereas; Adhesor and IRM presented the higher microleakage values. There were statistically significant differences between Clip and the others groups, while there were no statistically significant differences in microleakage between IRM, Adhesor, Coltosol and Cavit G. However the leakage scores of Clip and Cavit G were congruent (p = 0.454). CONCLUSION: Amongst the five materials, Clip exhibited a better sealing ability. PMID- 20297709 TI - Pulp polyp associated with a natal tooth: case report. AB - Natal teeth are an infrequent occurrence at birth. Often these teeth are extracted because they are very mobile and pose a risk of aspiration. This is a rare case in which a natal tooth was extracted by the pediatrician with his fingers. A root fragment remained and out of this developed a large pulp polyp. This relationship has not been previously reported. PMID- 20297710 TI - Outcome of dentigerous cysts treated with marsupialization. AB - OBJECTIVE: The aim of this study was to evaluate the results of dentigerous cysts in children treated with marsupialization. STUDY DESIGN: 35 dentigerous cysts from 35 children treated with marsupialization were included in the study. The age of the children ranged from 8 to 13 years old. RESULTS: The findings of our study showed that the outcome of dentigerous cysts treated with marsupialization is successful resulting with the eruption of teeth and regeneration of bone. Accordingly a successful outcome was achieved either with or without the help of an orthodontic treatment. Postoperative follow-ups were un-eventful in all patients during a 5 year period. CONCLUSION: The results of the present study demonstrate that marsupialization may be a better choice of treatment for dentigerous cysts in children rather than the standard treatment. PMID- 20297711 TI - Defining subphenotypes for tooth agenesis: does side matter? AB - OBJECTIVES: The etiology of tooth agenesis is still poorly understood. The identification of sub-populations with specific types of hypodontia (subphenotypes) would allow testing the specific hypothesis that certain genetic factors contribute to the specific subphenotype. The aim of this work was assessing a large cohort to verify if preferential tooth agenesis subphenotypes could be identified. METHOD: Panoramic radiographs of 1052 cases were examined and 1034 were used in this study. The presence of tooth agenesis was assessed in the study population. RESULTS: The frequency of tooth agenesis in the studied population was 3.77%. While bilateral cases did not differ in the frequency of agenesis by arch (p = 0.8), unilateral cases presented more commonly agenesis on the mandibular arch (p = 0.03). This result was clearly driven by the frequency of second premolar agenesis, which was the most common absent tooth in the studied population. Unilateral lower second premolar agenesis was found more often than bilateral agenesis (p = 0.047). CONCLUSIONS: Our findings that unilateral lower second premolar agenesis is more common than bilateral agenesis, with a trend for unilateral agenesis being more common on the right side may suggest specific genetic factors may be differentially expressed depending on the side. PMID- 20297712 TI - Wolf-Hirschhorn syndrome; oro-dental manifestations and management. AB - The major manifestations of the Wolf-Hirschhorn syndrome are developmental delay, short stature, mental impairment and epilepsy. Clefts of the lip and palate are sometimes present. Dental problems which are overshadowed by the major syndromic manifestations warrant appropriate management. We have documented an affected South African boy, discussed his dental management and reviewed the oro-dental implications of the disorder. PMID- 20297713 TI - Dental treatment under general anesthesia in healthy and medically compromised developmentally disabled children: a comparative study. AB - AIM: To compare the type, number of procedures and working time of dental treatment provided under dental general anesthesia (DGA) in healthy and medically compromised/developmentally disabled children (MCDD children). DESIGN: This cross sectional prospective study involved 80 children divided into two groups of 40 children each. Group 1 consisted of healthy and Group 2 consisted of MCDD children. RESULTS: Healthy children needed more working time than MCDD children, the means being 161 +/- 7.9 and 84 +/- 5.7 minutes, respectively (P = 0.0001). Operative dentistry and endodontic treatments showed a significant statistical difference (P = 0.0001). The means of procedures were 17 +/- 5.0 for healthy children and 11 +/- 4.8 for MCDD children (P = 0.0001). CONCLUSIONS: Healthy children needed more extensive dental treatment than MCDD children under DGA. The information from this sample of Mexican children could be used as reference for determining trends both within a facility as well as in comparing facilities in cross-population studies. PMID- 20297714 TI - A comparative evaluation of agents producing analgo-sedation in pediatric dental patients. AB - OBJECTIVE: Procedural sedation and analgesia (PSA) has reduced the need for general anesthesia (GA) for many surgical procedures in pediatric patients. The objective of this study was to evaluate the efficacy of four analgo-sedative combinations- midazolam plus ketamine (MK), midazolam plus tramadol (MT), promethazine plus tramadol (PT) and promethazine plus ketamine (PK) in facilitating dental treatment of uncooperative children. STUDY DESIGN: Thirty six uncooperative ASA type I children who required extensive dental treatment were randomly assigned to receive one of the four analgo-sedative combinations during each visit. A 4-stage cross-over design was adopted so that each child received all the four combinations. Safety was monitored through vital signs and side effects. RESULTS: The overall success was 81% with MK, 69% for PK, 67% for MT and 42% for PT and the difference between the success rates of these agents was statistically significant (p < 0.001). The required dental treatment could be successfully completed at least during 3 sessions in 23 children (62.2%). CONCLUSIONS: Segmental dental treatment under analgo-sedation can be considered as a viable alternative before considering patients for dental management under GA. MK and MT were found to be safe and effective for sedating pediatric dental patients. PMID- 20297715 TI - Effect of sodium fluoride mouth rinse on elastic properties of elastomeric chains. AB - OBJECTIVE: This study evaluated Sodium Fluoride mouth rinse effects on elastic properties of different elastomeric chains. STUDY DESIGN: In this in vitro experiment, two orthodontic chains were tested. In the first group, they were stored in artificial saliva for the entire duration, and in the second group they were immersed daily in 0.05% NaF mouth rinse for 1 minute, artificial saliva-NaF mixture for 30 minutes, and then in artificial saliva for the rest of the day. Specimens were tested at baseline, 1 hour 24 hours, 1, 2 and 3 weeks and then the displacement of specimens to obtain 150 g and 300 g, also the applied force after stretching them to 100% of their original length were evaluated. RESULTS: In contrast to force degradation, chains of both companies required more displacement to achieve both forces in the saliva-NaF mixture than saliva itself however the difference was only significant for the 300g force (P = 0.020). American Orthodontics chains required more displacement than Dentaurum chains to obtain both forces, also they had more load relaxation (P < 0.001). CONCLUSIONS: Daily use of NaF mouth rinse does not affect force degradation and the displacement of both chains to achieve conventional orthodontic forces, but for higher force levels the displacement increase is statistically significant. PMID- 20297716 TI - [Covalent complex of hyaluronan and serum-derived protein, SHAP is a functional molecule involved in inflammation: finding, structure, formation mechanism, and function of the complex]. PMID- 20297717 TI - [Formation mechanisms of endocrine secretory granules based on a high cholesterol membrane domain]. PMID- 20297718 TI - [Low-resolution structure analyses on protein complex by use of small-angle scattering technique]. PMID- 20297719 TI - [Resection, as an important step of homologous recombination]. PMID- 20297720 TI - [Mechanisms of salivary secretion from parotid acinar cells]. PMID- 20297721 TI - [Regulation of antiviral immunity on the mitochondrial outer membrane]. PMID- 20297722 TI - [Biogenesis of iron-sulfur clusters mediated by complex machineries]. PMID- 20297723 TI - [Subnuclear organization of genomes and gene regulation in the interphase nucleus]. PMID- 20297724 TI - [Sensitive and precise 2D-HPLC determination of D-amino acids in real biological samples]. PMID- 20297725 TI - [Current progress in methods for analysis of neuronal circuits]. PMID- 20297726 TI - [Novel method for the single-cell structural analysis of neuronal processes- labeling with viral vectors]. AB - Novel methods for Golgi-stain-like labeling of neurons have been developed by applying molecular biological techniques. Using replication-deficient adenovirus and Sindbis viral vectors expressing membrane-targeted green fluorescent protein (GFP), we visualized the neuronal processes of the infected neurons completely. Furthermore, when sufficiently diluted Sindbis virus solution was injected into the brain, the entire axonal arborization of infected neurons was recovered at a single cell level, giving new insights into neuronal networks. We have also developed the dendritic membrane-targeted GFP by using lentiviral vectors with a neuron-specific promoter. When the dendritic membrane-targeted GFP was applied to the transgenic animal production, the information input site, i.e., the dendrites, of a specific neuron group was visualized perfectly. Since neuronal processes, axons and dendrites, are key structures of neuronal information processing, the molecular biological techniques introduced here are useful for the morphological analysis of neuronal networks and thus helpful for understanding the functional design of the nervous system. PMID- 20297727 TI - [Analysis of multisynaptic neuronal pathways by using rabies virus]. AB - Transneuronal transport of neurotropic viruses is a useful tool for morphological analysis of the organization of multisynaptic neuronal pathways. Rabies virus is known to label neurons transsynaptically in a retrograde direction. Here, we examined the input systems of the primary motor cortex with respect to the somatotopic arrangement. Rabies virus was injected into the hindlimb, proximal forelimb, distal forelimb, and orofacial regions of the primary motor cortex in macaques, and the distribution patterns of neuronal labeling were analyzed in the prefrontal cortex, basal ganglia, and cerebellum. Four days after the injections, third-order neuron labeling was observed in various regions of the prefrontal cortex. After the viral injection into the proximal forelimb (shoulder, elbow) region, neuronal labeling was noted primarily in the dorsal region of the dorsolateral prefrontal cortex; on the other hand, after the viral injection into the distal forelimb (wrist, digits) region, neuronal labeling was preferentially distributed in the ventral region, with the highest density in the ventrolateral convexity. In the case of the orofacial injection, prefrontal neuron labeling was predominant not only in the ventrolateral convexity but also in the orbitofrontal cortex. However, the hindlimb injection resulted in relatively sparse neuron labeling as predominantly involving the neurons in the medial prefrontal cortex. With the 4-day postinjection period, neuronal labeling was noted in the striatum retrogradely via the motor cortico-basal ganglia loop. Two distinct sets of striatal neurons were labeled: one in the dorsal putamen and the other in the ventral striatum (ventromedial putamen and nucleus accumbens). The dorsal striatal labeling was somatotopically arranged, indicating that the hindlimb, orofacial, or forelimb region was located in the dorsal, ventral, or intermediate zone of the putamen, respectively. The distribution pattern of the ventral striatal labeling was essentially the same regardless of body part representation. Likewise, Purkinje cells of the cerebellar cortex were also labeled in a somatotopic fashion. Neuronal labeling from the forelimb representation was observed mainly in lobules III-VI and crus I. The proximal forelimb labeling was both rostral and lateral to the distal forelimb labeling. Yet, the hindlimb labeling was located both rostral and lateral to the proximal forelimb labeling. PMID- 20297728 TI - [Visualization of selective transsynaptic neural pathways using a genetic method]. AB - Functional logic employed by the nervous system for coding and processing information is determined by the wiring patterns among specific types of neurons. Therefore, detailed knowledge about neuronal circuits is essential for understanding the wide range of brain functions. In our opinion, an effective and long-awaited method for analyzing the neuronal connectivity patterns would be to selectively deliver tracers to specific types of neurons and simutaneously performing transsynaptic labeling of the target neurons. A unique property of plant lectins, such as wheat germ agglutinin (WGA) have the unique property of traveling across synapses and this property has been applied in classical neuroanatomical studies in order to label various neural pathways. In 1999, we developed a novel strategy that employs WGA cDNA as a transgene in order to visualize selective and functional neural pathways. Over the last decade, this method has gained popularity; further with substantial technical improvement and refinement, this method has been successfully employed for the analysis of various neural systems such as the olfactory, visual, gustatory, somatosensory, motor, and serotonergic systems. However, a few studies that employed this method failed because of the misinterpretation of the results. In this review, I summarize the principle, application, recent progress, and caveats of the WGA transgene technology. PMID- 20297729 TI - [Neural circuit analysis using isolated whole brain preparation]. AB - Many electrophysiological studies have been conducted on the 'limbic system', which is known to play a crucial role in mnemonic, emotional, and olfactory functions. Because of the difficulty in accessing such deep brain structures under in vivo conditions, in vitro brain slice preparations are often used. Recertly, an isolated whole brain preparation in which multi-synaptic circuits and the intracellular activity they generate are well preserved has also become available. In this paper, we described about the studies of the olfactory circuits by using this unique preparation. This experimental approach combines the advantages of the in vivo experimental condition with those of in vitro slice preparations, i.e. an intact synaptic network, excellent mechanical stability, and control over the ionic and biochemical extracellular environment. In particular, it provides easy access to the limbic system and preserves the neuronal network of the entorhinal-hippocampal loop. We used this preparation in combination with optical imaging performed using voltage-sensitive dyes in order to investigate how olfactory information is transferred from the olfactory bulb to the piriform, entorhinal and amygdaloid cortices. We visualized the propagation pattern of the neural activity after olfactory nerve stimulation and found that piriform and entorhinal activities converge in the amygdaloid cortex. This convergence may allow the amygdaloid cortex to integrate olfactory sensation with the information retained or processed in the entorhinal cortex. PMID- 20297730 TI - [Conditional cell targeting and reversible synapse silencing to study neural circuits]. AB - Brain function and plasticity are governed by interactions among neurons that are organized into highly diverse and complex networks. For understanding the mechanisms of information processing and plastic modification in the neural networks, experimental approaches to examine the effect of removing or silencing a restricted population of neuronal cells are useful. Since the mammalian brain is composed of numerous types of neurons, it is essential to establish techniques for precisely ablating or silencing specific neuronal cell types. Immunotoxins, which were originally designed as anticancer agents, are monoclonal-antibody conjugates containing toxins that kill cells bearing the target antigens. Conditional cell-ablation approaches based on the specificity of immunotoxins have been applied to elucidate the mechanisms underlying the operations and regulations of neural circuits. Tetanus neurotoxin inhibits synaptic transmission by cleaving VAMP2, which is essential for activity-dependent neurotransmitter release from presynaptic terminals. Transgenic animals that express tetanus neurotoxin under the control of a tetracycline-dependent inducible promoter system have been developed to reversibly control synaptic transmission in specific neuronal pathways. This review article describes the progress in the development of technologies that allow precise dissection of neural circuits, focusing on immunotoxin-mediated conditional cell targeting and tetanus neurotoxin mediated reversible synapse silencing. PMID- 20297731 TI - [Development and evaluation of new drugs and medical devices in Japan--standpoint of regulatory agency]. AB - Since 2004, the process of evaluation and approval review of new drugs and new medical devices in Japan has been undertaken by the Pharmaceutical and Medical Devices Agency (PMDA), which was established in the same year. PMDA conducts timely evaluation in order to ensure that public and healthcare professionals gain the maximun benefit of advanced, safe drugs and medical devices. The Japanese government has decided to reduce the "drug lag" by 2.5 years until fiscal year (FY) 2011. To achieve this goal, PMDA has undertaken some measures such as including increasing the number of reviewers reducing the period of development by significantly improving consultation services, developing guidance toward the introduction of prior assessment consultation system. Moreover, to improve of post-marketing safety measures, PMDA established a support system incorporating the data mining method. It is the PMDA's responsibility to put in its best efforts towards evaluateing various conflicting issues and appropriately balance them by assessing risks and benefits on the basis of the present scientific knowledge, in a manner that is most beneficial for public interest. Regulatory science thus provides a scientific basis for regulatory decisions. We strive to promote the regulatory science by establishing communication with external scientists and providing enhanced training to improve the staff's capability to apply regulatory science. PMID- 20297732 TI - [A case of intravascular malignant lymphomatosis presenting with epicornus syndrome and diagnosed by bone marrow biopsy]. AB - A-46-year-old woman admitted to our hospital because of numbness of bilateral lower limbs and urinary incontinence. The initial neurological examination showed sensory impairment below S1 level with urinary incontinence, indicating epicornus syndrome. Spinal MR imaging demonstrated unremarkable on conventional and enhanced images with Gd-DTPA. Cerebrospinal fluid examination revealed slightly elevated protein level without pleocytosis. Thereafter, subacute ascending myelopathy including flaccid paraparesis and urinary retention, developed. Because the patient had low grade fever, fatigue, weight loss and elevated serum soluble IL-2 receptor and LDH titers, we investigated her for lymphoma. Although lymphadenopathy or mass lesions were not found on whole-body CT scan, bone marrow biopsy showed the presence of inravascular large B-cell lymphoma (IVL). Thus the patient's progressive myelopathy was probably caused by IVL invasion. Ten days after the initiation of chemotherapy, her neurological symptoms transiently improved; however, her paraparesis and urinary incontinence gradually worsened thereafter, despite of treatment. IVL often presents with neurological manifestations, including myelopathy. There have been a few reports of IVL presenting with lower lumbar spinal cord and conus medullaris. It should be noted that IVL can cause unidentified progressive ascending myelopathy without positive MRI findings. PMID- 20297733 TI - [Binocular diplopia and ptosis due to snakebite (Agkistrodon blomhoffi "mamushi") -a case report]. AB - We treated a patient who developed binocular diplopia and ptosis after being bitten by an Agkistrodon blomhoffi (mamushi). The patient was a 49-year-old man who presented with binocular diplopia after the snakebite on the second finger of his right hand. He experienced local pain and swelling and a few hours later, he developed diplopia. In the primary position he had no tropia. On the basis the ocular angle of deviation measured by a Hess chart test, he was diagnosed with paresis of the medial rectus muscle paresis. Binocular diplopia persisted for 2 weeks. The venom of A. blomhoffi venom mainly consists of hemolytic toxins, but it also contains 2 types of neurotoxins--an alpha-toxin and a beta-toxin. Neurotoxins affects the neuromuscular junction (NMJ). The alpha-toxin acts postsynaptic inhibition as a competitive inhibitor of acetylcholine and causes postsynaptic inhibition; these effects are similar to those of the anti acetylcholine receptor antibody identified in patients with myasthenia gravis. The beta-toxin inhibits acetylcholine release by disrupting the presynaptic membrane, and thus, its effects cannot be blocked by the anticholinesterase edrophonium chloride. Although both antiserum and cepharanthine are widely used for the treatment of snakebites, there is no evidence of a specific effective therapy for the eye manifestation after snakebite. However, it these manifestation improves in about 2 weeks without any specific treatment. Our case suggested that the occurrence of subjective binocular diplopia without objective tropia could be caused by snakebite. PMID- 20297734 TI - [Cervical MRI findings of delayed radiation myelopathy with hemiparesis]. PMID- 20297735 TI - [One hundred books which built up neurology (39)--Aitkin "Elements of physiology" (1838)]. PMID- 20297736 TI - [Recent progress in the development of disease-modifying therapies for Alzheimer's disease]. AB - Alzheimer's disease (AD) is a neurodegenerative disorder characterized by senile plaques and neurofibrillary tangles in the brain. Currently available therapies for AD may slow cognitive decline but do not alter underlying disease processes. Amyloid beta protein (Abeta), the major component of senile plaques, is a 40 to 43 amino acid peptide cleaved from amyloid precursor protein (APP) by beta secretase and gamma-secretase and has been implicated as the primary cause of AD. According to the amyloid hypothesis, extensive efforts have been made to find drugs that can reduce brain Abeta accumulation, including prevention of Abeta aggregation, inhibition of APP processing and acceleration of Abeta degradation. Anti-Abeta immunotherapy has attracted considerable attention as the most exciting treatment approach for AD over the last decade, but some patients showed no clinical improvement despite clear reductions of Abeta. More recently, alternative approaches have begun to target the microtubule binding protein tau, a component of neurofibrillay tangles. The combination of therapies against Abeta and tau may be a promising therapeutic strategy for AD. PMID- 20297737 TI - [Generation of epilepsy animal model bearing a genetic abnormality identified in autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) of humans]. AB - Nocturnal frontal lobe epilepsy is seen exclusively during sleep and is characterized by three distinct seizure phenotypes: paroxysmal arousals, paroxysmal dystonia, and episodic wandering. Mutations of CHRNA4, CHRNB2, or CHRNA2 genes encoding alpha4, beta2 or alpha2 subunits of neuronal nicotinic ACh receptor (nAChR) have been identified in the individuals with sporadic type NFLE and pedigrees with autosomal dominant type of NFLE (ADNFLE). In the past decade, various electrophysiological studies have analyzed the functional abnormalities of ADNFLE/NFLE mutant nAChR; however, the detailed pathogenesis of ADNFLE/NFLE has remained to be clarified. Therefore, to explore the pathogenesis of ADNFLE/NFLE, genetic animal models harboring ADNFLE mutant Chrna4 genes have recently been established. The face, construct and predictive validities have been demonstrated in a transgenic rat strain bearing the S284L mutant Chrna4 gene. The in vivo analyses of the functional abnormalities using genetic ADNFLE/NFLE animal models suggest the putative mechanisms of the ADNFLE/NFLE seizure onset during slow wave sleep. PMID- 20297738 TI - [Toward understanding the molecular mechanism of brain function by molecular and neural circuit elucidation of the C. elegans nervous system]. AB - Recent studies have provided extensive molecular insights into neuronal polarity establishment in vitro. However, it is still poorly understood how the corresponding phenomenon occurs and leads to correct localization of synaptic components in vivo. RIA interneurons in the nematode C. elegans have a neurite clearly divided into pre- and post-synaptic regions and act as a pivotal component of the neural circuit for thermotaxis behavior, thereby providing a suitable model to elucidate these issues. We found that loss of Inositol Monophosphatase (IMPase) encoded by the ttx-7 gene, an Inositol-producing enzyme regarded as a bipolar disorder-relevant molecule for its Lithium sensitivity, causes defects in thermotaxis behavior and localization of synaptic proteins in RIA neurons in vivo. Both behavioral and localization defects in ttx-7 mutants were rescued by expression of IMPase at the adult stage and Inositol application, and were mimicked by Lithium application in wild type animals. These results suggest that IMPase is required in the mature nervous system for regulating correct localization of synaptic components in the central interneurons in order for animals to behave properly. PMID- 20297739 TI - [Identification of a gene regulating "behavioral despair" in mice]. AB - We found that CS mice exhibit an extremely low immobility time (almost no immobility) in both the tail suspension test (TST) and forced swimming test (FST). In these tests, animals are subjected to the short-term, inescapable stress of being suspended by their tail or being forced to swim in a water-filled cylinder. In such situations, the animals rapidly adopt a characteristic immobile posture that has been named "behavioral despair" on the assumption that the animals have given up hope of escaping. These tests have been widely used for assessing antidepressant activity and depression-like behavior. Quantitative trait locus (QTL) mapping using CS and C57BL/6J mice revealed significant QTLs on chromosomes (Chrs) 4 (FST) and 5 (TST and FST). To identify the quantitative trait gene on Chr 5, we narrowed the QTL interval to 0.5 Mb using several congenic and subcongenic strains. Ubiquitin-specific peptidase 46 (Usp46) with a lysine codon deletion was located in this region. This deletion affected nest building, muscimol-induced righting reflex and anti-immobility effects of imipramine. The muscimol-induced current in the hippocampal CA1 pyramidal neurons and hippocampal expression of the 67-kDa isoform of glutamic acid decarboxylase significantly decreased in the Usp46 mutant mice compared to control mice. All these phenotypes were rescued in transgenic mice with bacterial artificial chromosomes containing wild-type Usp46. Thus, Usp46 affects "behavioral despair" and it is implicated in the regulation of GABA action. PMID- 20297740 TI - Oral health: the silent epidemic. PMID- 20297741 TI - How healthy could a state be? AB - OBJECTIVE: We predicted the amount of health outcome improvement any state might achieve if it could reach the highest level of key health determinants any individual state has already achieved. METHODS: Using secondary county-level data on modifiable and nonmodifiable health determinants from 1994 to 2003, we used regression analysis to predict state age-adjusted mortality rates in 2000 for those younger than age 75, under the scenario of each state's "ideal" predicted mortality if that state had the best observed level among all states of modifiable determinants. RESULTS: We found considerable variation in predicted improvement across the states. The state with the lowest baseline mortality, New Hampshire, was predicted to improve by 23% to a mortality rate of 250 per 100,000 population if New Hampshire had the most favorable profile of modifiable health determinants. However, West Virginia, with a much higher baseline, would be predicted to improve the most-by 46% to 254 per 100,000 population. Individual states varied in the pattern of specific modifiable variables associated with their predicted improvement. CONCLUSIONS: The results support the contention that health improvement requires investment in three major categories: health care, behavioral change, and socioeconomic factors. Different states will require different investment portfolios depending on their pattern of modifiable and nonmodifiable determinants. PMID- 20297742 TI - The politics of achievable mortality. PMID- 20297743 TI - Transitions clinic: creating a community-based model of health care for recently released California prisoners. AB - Most California prisoners experience discontinuity of health care upon return to the community. In January 2006, physicians working with community organizations and representatives of the San Francisco Department of Public Health's safety-net health system opened the Transitions Clinic (TC) to provide transitional and primary care as well as case management for prisoners returning to San Francisco. This article provides a complete description of TC, including an illustrative case, and reports information about the recently released individuals who participated in the program. From January 2006 to October 2007, TC saw 185 patients with chronic medical conditions. TC patients are socially and economically disenfranchised; 86% belong to ethnic minority groups and 38% are homeless. Eighty-nine percent of patients did not have a primary care provider prior to their incarceration. Preliminary findings demonstrate that a community based model of care tailored to this disenfranchised population successfully engages them in seeking health care. PMID- 20297745 TI - Influenza vaccination rates of children in households with high-risk adults. AB - OBJECTIVES: Household contacts of people at high risk for influenza complications should receive yearly influenza vaccination to reduce potential viral transmission. We evaluated influenza vaccine coverage among children to determine whether or not living with a high-risk adult predicts the likelihood of being vaccinated. METHODS: Using the 2006 National Health Interview Survey, we examined influenza vaccination rates among children (aged 1-17 years) who did and did not reside in a household with an adult at high risk for influenza-related complications. RESULTS: Among 24,195 sampled families, there were 8,976 high-risk adults, 18.9% of whom reported living with a person 17 years of age of younger. Influenza vaccination rates by age group among children living with high-risk adults were 41.7% (1 year), 30.3% (2-4 years), and 20.0% (5-17 years). Unadjusted influenza vaccination rates were significantly higher for school-aged children who lived with a high-risk adult compared with those who did not (20.0% vs. 15.0%, p < 0.001). Among children younger than 5 years of age, for whom vaccination was universally recommended at the time of the survey, the rates did not differ. After adjusting for the child's age, gender, race, insurance coverage, medical visits, and chronic conditions, children who lived with a high risk adult were not statistically more likely than those who did not live with a high-risk adult to receive influenza vaccination (odds ratio = 1.16, 95% confidence interval 0.99, 1.36). CONCLUSIONS: Children had low rates of influenza vaccination, and those who lived with high-risk adults were not significantly more likely to be vaccinated. Clinicians caring for high-risk adults should remind eligible household contacts to receive influenza vaccine. PMID- 20297744 TI - Impact of non-pharmaceutical interventions on URIs and influenza in crowded, urban households. AB - OBJECTIVES: We compared the impact of three household interventions-education, education with alcohol-based hand sanitizer, and education with hand sanitizer and face masks-on incidence and secondary transmission of upper respiratory infections (URIs) and influenza, knowledge of transmission of URIs, and vaccination rates. METHODS: A total of 509 primarily Hispanic households participated. Participants reported symptoms twice weekly, and nasal swabs were collected from those with an influenza-like illness (ILI). Households were followed for up to 19 months and home visits were made at least every two months. RESULTS: We recorded 5034 URIs, of which 669 cases reported ILIs and 78 were laboratory-confirmed cases of influenza. Demographic factors significantly associated with infection rates included age, gender, birth location, education, and employment. The Hand Sanitizer group was significantly more likely to report that no household member had symptoms (p < 0.01), but there were no significant differences in rates of infection by intervention group in multivariate analyses. Knowledge improved significantly more in the Hand Sanitizer group (p < 0.0001). The proportion of households that reported > or = 50% of members receiving influenza vaccine increased during the study (p < 0.001). Despite the fact that compliance with mask wearing was poor, mask wearing as well as increased crowding, lower education levels of caretakers, and index cases 0-5 years of age (compared with adults) were associated with significantly lower secondary transmission rates (all p < 0.02). CONCLUSIONS: In this population, there was no detectable additional benefit of hand sanitizer or face masks over targeted education on overall rates of URIs, but mask wearing was associated with reduced secondary transmission and should be encouraged during outbreak situations. During the study period, community concern about methicillin-resistant Staphylococcus aureus was occurring, perhaps contributing to the use of hand sanitizer in the Education control group, and diluting the intervention's measurable impact. PMID- 20297746 TI - Newborn hearing screening and follow-up: are children receiving recommended services? AB - OBJECTIVES: Newborn hearing screening programs have been implemented by all 50 states and most U.S. territories to detect hearing loss in infants and prevent delays in speech, language, and social and emotional development. To monitor progress toward national goals, the Centers for Disease Control and Prevention (CDC) collects data from state and territorial programs. This article summarizes findings from the CDC Early Hearing Detection and Intervention (EHDI) Hearing Screening and Follow-up Survey (HSFS) and provides a summary of recent efforts to identify infants with hearing loss in the U.S. METHODS: The HSFS was sent to representatives of U.S. EHDI programs to gather aggregate screening, diagnostic, intervention, and demographic data for 2005 and 2006. We analyzed these data to evaluate progress toward national goals. RESULTS: In 2005 and 2006, more than 90% of infants were screened for hearing loss. Of these infants, 2% in both years did not pass their final screening. Out of those not passing the final screening, approximately two-thirds were not documented as having a diagnostic finding. In both years, the reason reported for the majority of infants was loss to follow up/loss to documentation (LFU/LTD). Although the majority of infants with permanent hearing loss were receiving intervention, more than 30% were classified as LFU/LTD and could not be documented as receiving intervention services. CONCLUSIONS: The HSFS enables the collection of more complete data that highlight the progress in screening infants for hearing loss. However, data indicate improvements are needed to reduce LFU/LTD and meet the national benchmarks. PMID- 20297747 TI - Condoms for dual protection: patterns of use with highly effective contraceptive methods. AB - OBJECTIVES: U.S. women experience high rates of unplanned pregnancy and sexually transmitted infections (STIs), yet they seldom combine condoms with highly effective contraceptives for optimal protection. Because oral contracep tives (OCs) have been the predominant form of highly effective contraceptio in the U.S., it is unknown whether condom use is similarly low with increasingly promoted user-independent methods. METHODS: We used weighted data from the National Survey of Family Growth to assess condom use odds among women relying on OCs vs. user-independent methods (i.e., injectibles, intrauterine devices, and implants). We also estimated the expected reduction in unplanned pregnancies and abortions if half or all of the women currently using a single highly effective method also used condoms. RESULTS: Across every demographic subgroup based on age, partner status, race/ethnicity, household income, and education, condom use prevalence was lower for women relying on user-independent methods vs. OCs. Multivariable models for adult women also revealed a significant reduction within most demographic subgroups in the odds of condom use among women relying on user independent methods vs. OCs. Population estimates suggested that if half of all women using highly effective methods alone also used condoms, approximately 40% of unplanned pregnancies and abortions among these women could be prevented, for an annual reduction of 393,000 unplanned pregnancies and nearly 76,000 abortions. If all highly effective method users also used condoms, approximately 80% of unplanned pregnancies and abortions among these women could be prevented, for an annual reduction of 786,000 unplanned pregnancies and nearly 152,000 abortions. CONCLUSIONS: Adding condoms to other methods should be considered seriously as the first line of defense against unplanned pregnancy and STls. This analysis can serve to target interventions where dual-method promotion is needed most. PMID- 20297748 TI - Trends in prevalence of obesity and overweight among children enrolled in the New York State WIC program, 2002-2007. AB - OBJECTIVES: We examined recent overweight and obesity trends in a multiethnic population of low-income preschool children. METHODS: We defined overweight as sex-specific body mass index (BMI)-forage > or = 85th and < 95th percentile and obesity as sex-specific BMI-for-age > or = 95th percentile, and calculated them using demographic data and randomly selected height and weight measurements that were recorded while 2- to < 5-year-old children were enrolled in the New York State (NYS) Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) during 2002-2007. RESULTS: Obesity prevalence peaked at 16.7% in 2003, declined from 2003 through 2005, and stabilized at 14.7% through 2007. Among both boys and girls, the downward trend in annual prevalence of obesity was evident only among Hispanic children (22.8% boys and 20.9% girls in 2002 vs. 19.3% boys and 17.5% girls in 2007) and non-Hispanic black children (15.6% boys and 14.2% girls in 2002 vs. 13.6% boys and 12.4% girls in 2007). In contrast, the annual prevalence estimate for overweight showed an increasing trend from 2002 through 2007. CONCLUSIONS: These results showed a slight decline in prevalence of childhood obesity and a continuing rise in prevalence of childhood overweight among children enrolled in the NYS WIC program during 2002-2007. Future research should investigate the extent to which the slight decline in childhood obesity prevalence may be attributable to population-based and high-risk obesity prevention efforts in NYS. PMID- 20297749 TI - The association of workplace hazards and smoking in a U.S. multiethnic working class population. AB - OBJECTIVE: We investigated the extent to which smoking status was associated with exposure to occupational (e.g., dust, chemicals, noise, and ergonomic strain) and social (e.g., abuse, sexual harassment, and racial discrimination) workplace hazards in a sample of U.S. multiethnic working-class adults. METHODS: United for Health is a cross-sectional study designed to investigate the combined burden of occupational and social workplace hazards in relation to race/ethnicity, gender, and wage and to evaluate related health effects in a working-class population. Using validated measures, we collected data from 1,282 multiethnic working-class participants using audio computer-assisted interviews. We used multiple imputation methods to impute data for those missing data. Crude and adjusted logistic odds ratios (ORs) were modeled to estimate ORs and 95% confidence intervals (CIs). RESULTS: The prevalence of smoking was highest among non Hispanic white workers (38.3%) and lowest for foreign-born workers (13.1%). We found an association between racial discrimination and smoking (OR = 1.12, 95% CI 1.01, 1.25). The relationship between smoking and sexual harassment, although not significant, was different for black women compared with men (OR = 1.79, 95% CI 0.99, 3.22). We did not find any associations by workplace abuse or by any of the occupational hazards. CONCLUSION: These results indicate that racial discrimination might be related to smoking in working-class populations and should be considered in tobacco-control efforts that target this high-risk population. PMID- 20297750 TI - Comparing lead poisoning risk assessment methods: census block group characteristics vs. zip codes as predictors. AB - OBJECTIVE: We determined which children should be tested for elevated blood lead levels (BLLs) in the face of financial and practical barriers to universal screening efforts and within 2009 Centers for Disease Control and Prevention recommendations allowing health departments to develop BLL screening strategies. METHODS: We used the Michigan database of BLL tests from 1998 through 2005, which contains address, Medicaid eligibility, and race data. Linking addresses to U.S. Census 2000 data by block group provided neighborhood sociodemographic and housing characteristics. To derive an equation predicting BLL, we treated BLL as a continuous variable and used Hierarchical Linear Modeling to estimate the prediction equation. RESULTS: Census block groups explained more variance in BLL than tracts and much more than dichotomized zip code risk (which is current pediatric practice). Housing built before 1940, socioeconomic status and racial/ethnic characteristics of the block group, child characteristics, and empirical Bayesian residuals explained more than 41% of the variance in BLL during 1998-2001. By contrast, zip code risk and Medicaid status only explained 15% of the BLL variance. An equation using 1998-2001 BLL data predicted well for BLL tests performed in 2002-2005. While those who received BLL tests had above average risk, this method produced minimal bias in using the prediction equation for all children. CONCLUSIONS: Our equation offers better specificity and sensitivity than using dichotomized zip codes and Medicaid status, thereby identifying more high-risk children while also offering substantial cost savings. Our prediction equation can be used with a simple Internet-based program that allows health-care providers to enter minimal information and determine whether a BLL test is recommended. PMID- 20297751 TI - Epidemiology of West Nile virus in the highly epidemic state of North Dakota, 2002-2007. AB - OBJECTIVES: West Nile virus (WNV) continues to cause seasonal epidemics of neuroinvasive disease and febrile illness, which have been most dramatic in the central plains states. We studied the epidemiology of WNV disease in North Dakota (ND), a highly epidemic state, six years following its first appearance in the state. METHODS: We analyzed information from cases of WNV disease reported to the ND Department of Health during August 2002 through December 2007. RESULTS: A total of 1246 cases of WNV disease were reported in ND; 183 cases experienced neuroinvasive disease, including meningitis, encephalitis, or acute flaccid paralysis. Risk factors associated with developing neuroinvasive disease rather than West Nile fever included older age, male gender, and residence in a rural area. Annual cumulative incidence of neuroinvasive disease in ND ranged from 0.3 per 100,000 population to 14.6 per 100,000 population. CONCLUSIONS: Annual cumulative incidence rates of West Nile neuroinvasive disease suggest that this region offers favorable conditions for its continued enzootic transmission, which highlights the need for improved targeted prevention measures, particularly for rural areas of the state. PMID- 20297752 TI - Characteristics of Asian and Pacific Islanders admitted to U.S. drug treatment programs in 2005. AB - OBJECTIVE: We determined how Asian and Pacific Islanders (APIs) differ from clients from other ethnic groups in regard to drug use and admissions to drug treatment programs. METHODS: We used national survey and treatment admissions data to characterize drug problems and first-time adult admissions to publicly funded drug treatment programs in the U.S. in 2005. RESULTS: APIs accounted for 1.9% of illicit drug use in U.S. adults and for 1.3% of adult clients entering drug treatment for the first time. Compared with other ethnic groups, APIs were significantly more likely to be entering treatment for the first time. Stimulants were the primary drug problem for 57.3% of API first-time treatment clients, a significantly greater proportion than other ethnic groups. This figure had increased from 45.3% in 2001, significantly greater than the increase among Caucasian or African American clients. API first-time admissions had used drugs less frequently (13.6 days in the prior 30 days), began drug use at a slightly older age (mean = 20.7 years), and had a shorter period between start of use and first admission (mean = 9.4 years) than other racial/ethnic groups. CONCLUSION: Stimulant use was the predominant problem of API clients entering treatment for the first time. APIs were underrepresented in the treatment system relative to their share of the population with drug problems. Diverse groups were aggregated to form the API category. Information on APIs needs to be disaggregated to develop more culturally appropriate and effective treatment. PMID- 20297753 TI - Assessing the impact of the Health Center Growth Initiative on health center patients. AB - OBJECTIVES: In 2001, the Health Center Growth Initiative was launched to increase access to primary health-care services through the expansion of the health center program. We examined the impact this initiative had on the number and types of patients seen by health centers, as well as the health center characteristics significantly associated with service expansions. METHODS: We conducted secondary and time-trend analyses of the Uniform Data System, an annual dataset submitted to the Bureau of Primary Health Care by all federally qualified health centers. We performed trend and multivariable analyses to examine the impact of the initiative on health center performance. RESULTS: Health centers that received both new access points and expanded medical capacity funding saw the most rapid growth in patients. These centers experienced a 58% increase in total number of patients and a 60% increase in total number of encounters, compared with 10% and 8%, respectively, for centers receiving no funding at all. CONCLUSIONS: were unchanged even after controlling for other health center characteristics. CONCLUSIONS: Public funding is critical to sustaining and expanding health center services to the nation's vulnerable populations. PMID- 20297754 TI - The changing face of U.S. funding for HIV programs in resource-limited settings. PMID- 20297755 TI - Horizons: looking back, moving forward. PMID- 20297756 TI - Reducing HIV-related stigma: lessons learned from Horizons research and programs. AB - Since the early years of the human immunodeficiency virus (HIV) epidemic, stigma has been understood to be a major barrier to successful HIV prevention, care, and treatment. This article highlights findings from more than 10 studies in Asia, Africa, and Latin America-conducted from 1997 through 2007 as part of the Horizons program-that have contributed to clarifying the relationship between stigma and HIV, determining how best to measure stigma among varied populations, and designing and evaluating the impact of stigma reduction-focused program strategies. Studies showed significant associations between HIV-related stigma and less use of voluntary counseling and testing, less willingness to disclose test results, and incorrect knowledge about transmission. Programmatic lessons learned included how to assist institutions with recognizing stigma, the importance of confronting both fears of contagion and negative social judgments, and how best to engage people living with HIV in programs. The portfolio of work reveals the potential and importance of directly addressing stigma reduction in HIV programs. PMID- 20297757 TI - Addressing gender dynamics and engaging men in HIV programs: lessons learned from Horizons research. AB - In the field of human immunodeficiency virus (HIV) prevention, there has been increasing interest in the role that gender plays in HIV and violence risk, and in successfully engaging men in the response. This article highlights findings from more than 10 studies in Asia, Africa, and Latin America--conducted from 1997 through 2007 as part of the Horizons program--that have contributed to understanding the relationship between gender and men's behaviors, developing useful measurement tools for gender norms, and designing and evaluating the impact of gender-focused program strategies. Studies showed significant associations between support for inequitable norms and risk, such as more partner violence and less condom use. Programmatic lessons learned ranged from insights into appropriate media messages, to strategies to engage men in critically reflecting upon gender inequality, to the qualities of successful program facilitators. The portfolio of work reveals the potential and importance of directly addressing gender dynamics in HIV- and violence-prevention programs for both men and women. PMID- 20297758 TI - Implementing programs for the prevention of mother-to-child HIV transmission in resource-constrained settings: Horizons studies, 1999-2007. AB - An estimated 430,00 new human immunodeficiency virus (HIV) infections occurred among children younger than 15 years of age in 2008, most in sub-Saharan Africa and most due to mother-to-child transmission (MTCT). In marked contrast, MTCT of HIV has been virtually eliminated in well-resourced settings through the use of combinations of antiretroviral (ARV) drugs for the mother during pregnancy and labor and for the infant postpartum; cesarean delivery to reduce the infant's exposure to trauma and infection in the birth canal; and formula feeding to protect the infant from transmission from breastfeeding. While effective, these interventions are costly and require strong health-care systems. From 1999 to 2003, Horizons conducted operations research to determine how interventions successful in the clinical trial setting would translate to the real-world environments of maternal and child healthcare delivery in low-resource settings. A second set of Horizons studies (2004-2007) sought to address gaps in adherence to ARV prophylaxis; examine roles of family planning in prevention of MTCT (PMTCT) programs; show the value of psychosocial support for HIV-positive mothers; and identify ways to improve the quality of care and follow-up for women in the postpartum period. This article provides an assessment of the findings of Horizons studies on PMTCT interventions from 1999 to 2007 and identifies needs for follow-on efforts. PMID- 20297759 TI - Access to antiretroviral therapy for adults and children with HIV infection in developing countries: Horizons studies, 2002-2008. AB - The Access-to-Treatment research initiative of the Population Council's Horizons program undertook 11 projects across Asia and sub-Saharan Africa from 2002 to 2008. The projects included a variety of cross-sectional exploratory studies, situation analyses, and longitudinal randomized, controlled intervention studies that examined service delivery, community awareness, health-seeking behaviors, adherence, cost, and other factors affecting treatment for adults and children infected with human immunodeficiency virus (HIV). This article summarizes the key findings and lessons learned from these projects, and examines cross-cutting issues such as stigma, quality of life, and sexual-risk behaviors among people living with HIV and acquired immunodeficiency syndrome on antiretroviral therapy. The article concludes with recommendations for evidence-based programming and future research around treatment for both children and adults. PMID- 20297760 TI - HIV vulnerability of men who have sex with men in developing countries: Horizons studies, 2001-2008. AB - While male-to-male sexual behavior has been recognized as a primary risk factor for human immunodeficiency virus (HIV), research targeting men who have sex with men (MSM) in less-developed countries has been limited due to high levels of stigma and discrimination. In response, the Population Council's Horizons Program began implementing research activities in Africa and South America beginning in 2001, with the objectives of gathering information on MSM sexual risk behaviors, evaluating HIV-prevention programs, and informing HIV policy makers. The results of this nearly decade-long program are presented in this article as a summary of the Horizons MSM studies in Africa (Senegal and Kenya) and Latin America (Brazil and Paraguay), and include research methodologies, study findings, and interventions evaluated. We also discuss future directions and approaches for HIV research among MSM in developing countries. PMID- 20297761 TI - Improving the lives of vulnerable children: implications of Horizons research among orphans and other children affected by AIDS. AB - From 1997 through 2007, the Horizons program conducted research to inform the care and support of children who had been orphaned and rendered vulnerable by acquired immunodeficiency syndrome in sub-Saharan Africa. Horizons conducted studies in Kenya, Malawi, Rwanda, South Africa, Uganda, Zambia, and Zimbabwe. Research included both diagnostic studies exploring the circumstances of families and communities affected by human immunodeficiency virus (HIV) and evaluations of pioneering intervention strategies. Interventions found to be supportive of families included succession planning for families with an HIV-positive parent, training and supporting youth as caregivers, and youth mentorship for child headed households. Horizons researchers developed tools to assess the psychosocial well-being of children affected by HIV and outlined key ethical guidelines for conducting research among children. The design, implementation, and evaluation of community-based interventions for orphans and vulnerable children continue to be a key gap in the evidence base. PMID- 20297762 TI - Debating the health effects of DDT: Thomas Jukes, Charles Wurster, and the fate of an environmental pollutant. PMID- 20297763 TI - The health privacy provisions in the American Recovery and Reinvestment Act of 2009: implications for public health policy and practice. PMID- 20297764 TI - Promoting implementation of a school district sexual health education policy through an academic-community partnership. PMID- 20297765 TI - Cost analysis of influenza vaccine administration in Fayette County, Kentucky, 2005-2007. PMID- 20297766 TI - Site isolation of emitters within cross-linked polymer nanoparticles for white electroluminescence. AB - The use of cross-linked polymer nanoparticles was explored to achieve site isolation of different emitters within a single emissive layer in an electroluminescent device. Encapsulation of the iridium emitters within the polymer nanoparticles led to the desired effect with minimal energy transfer from high bandgap chromophores to lower bandgap ones. The nanoparticles were easily dispersed in organic solvent for film casting while preserving particle shape. They behave as light emitting "inks", enabling the tuning of electroluminescence through simple changes in the ratios of nanoparticles in the emissive film. PMID- 20297767 TI - Electrochemical synthesis and catalytic property of sub-10 nm platinum cubic nanoboxes. AB - We report an electrochemical synthesis of ultrafine Pt cubic nanoboxes from Pt-on Ag heteronanostructures. These cubic nanoboxes have an average edge length of about 6 nm and a wall thickness of 1.5 nm. Several reaction parameters including the profile of applied potentials were examined to develop an optimal procedure for controlling the size, shape, and surface morphology of the nanoboxes. A strong shape-dependent catalytic property is observed for Pt cubic nanoboxes, which is 1.5 times more active than hollow spheres in terms of turn over frequency for catalytic oxidation of methanol. PMID- 20297768 TI - Using the pyridine and quinuclidine scaffolds for superbases: a DFT study. AB - 2,6-Disubstituted pyridines and 2,6,7-trisubstituted quinuclidines are screened as potential strong bases. The relative proton affinities of the bases are computed at PBE1PBE/6-311G(d,p) in the gas phase and in the solution phase (THF) at the same level with the IEFPCM treatment. Basicities are enhanced by the lone pair possessing atoms on the substituents' arms stabilizing the conjugate acid through hydrogen bonding. The strongest bases are 2,6-bis(3-methoxy-2-furyl)-4 dimethylaminopyridine and 2,6-di(2-dimethylaminoethyl)pyridine. PMID- 20297769 TI - Molecular mechanism of acid-catalyzed hydrolysis of peptide bonds using a model compound. AB - The stability of peptide bonds is a critical aspect of biological chemistry and therapeutic protein applications. Recent studies found elevated nonenzymatic hydrolysis in the hinge region of antibody molecules, but no mechanism was identified. As a first step in providing a mechanistic interpretation, this computational study examines the rate-determining step of the hydrolytic reaction of a peptide bond under acidic pH by a path sampling technique using a model compound N-MAA. Most previous computational studies did not include explicit water molecules, whose effects are significant in solution chemistry, nor did they provide a dynamic picture for the reaction process in aqueous conditions. Because no single trajectory can be used to describe the reaction dynamics due to fluctuations at finite temperatures, a variant version of the transition path sampling technique, the aimless shooting algorithm, was used to sample dynamic trajectories and to generate an ensemble of transition trajectories according to their statistical weights in the trajectory space. Each trajectory was computed as the time evolution of the molecular system using the Car-Parrinello molecular dynamics technique. The likelihood maximization procedure and its modification were used in extracting dynamically relevant degrees of freedom in the system, and approximations of the reaction coordinate were compared. Its low log likelihood score and poor p(B) histogram indicate that the C-O distance previously assumed as the reaction coordinate for the rate-determining step is inadequate in describing the dynamics of the reaction. More than one order parameter in a candidate set including millions of geometric quantities was required to produce a convergent reaction coordinate model; its involvement of many degrees of freedom suggests that this hydrolytic reaction step is very complex. In addition to affecting atoms directly involved in bond-making and breaking processes, the water network also has determining effects on the hydrolytic reaction, a fact that is manifest in the expression of the one dimensional best-ranked reaction coordinate, which includes three geometric quantities. The p(B) histograms were computed to verify the results of the likelihood maximization and to verify the accuracy of approximation to the "true" reaction coordinate. PMID- 20297770 TI - Hydrogelation through self-assembly of fmoc-peptide functionalized cationic amphiphiles: potent antibacterial agent. AB - The present work reports a new class of antibacterial hydrogelators based on anti inflammatory N-fluorenyl-9-methoxycarbonyl (Fmoc) amino acid/peptides functionalized cationic amphiphiles. These positively charged hydrogelators were rationally designed and developed by the incorporation of a pyridinium moiety at the C-terminal of Fmoc amino acid/peptides, because the pyridinium-based amphiphiles are a known antibacterial agent due to their cell membrane penetration properties. The Fmoc amino acid/peptide-based cationic amphiphiles efficiently gelate (minimum gelation concentration approximately 0.6-2.2%, w/v) water at room temperature. Judicious variation of amino acid and their sequences revealed the architectural dependence of the molecules on their gelation ability. Several microscopic techniques like field-emission scanning electron microscopy (FESEM) and atomic force microscopy (AFM) were used to obtain the visual insight of the morphology of the gel network. A number of spectroscopic techniques like circular dichroism, FTIR, photoluminescence, and XRD were utilized to know the involvement of several noncovalent interactions and participation of the different segments of the molecules during gelation. Spectroscopic results showed that the pi-pi interaction and intermolecular hydrogen bonding are the major responsible factors for the self-assembled gelation process that are oriented through an antiparallel beta-sheet arrangement of the peptide backbone. These Fmoc-based cationic molecules exhibited efficient antibacterial activity against both Gram-positive and Gram-negative bacteria. PMID- 20297771 TI - Multi-approach electron paramagnetic resonance investigations of UV-photoinduced Ti(3+) in titanium oxide-based gels. AB - EPR investigations of the photoreduction of Ti(4+) into Ti(3+) under UV irradiation were carried out on three titanium-based materials for which the initial concentration of Ti(4+) was defined in the ternary phase diagram (TiOCl(2), H(2)O, DMF). The kinetics of this photoreduction was monitored at 200 K and related to the initial concentration of Ti(4+) in the solution. This study was complemented by a multi-approach EPR method (pulsed electron paramagnetic resonance (EPR), pulsed electron nuclear double resonance, and hyperfine sublevel correlation spectroscopy (HYSCORE)) with the aim of probing the proton environment of the Ti(3+) ions. Indeed, many species such as H(2)O, OH(-), HCOO( ) are located in the immediate vicinity of Ti(3+). Although we found that a distribution of g tensors was involved, for simplicity, two types of g tensor were used to describe the main features of the EPR signal related to the paramagnetic ions. Additionally, we have evidenced that two kinds of protons are identified next to Ti(3+) species, with specific distances determined from the hyperfine coupling parameters obtained by the HYSCORE method. PMID- 20297772 TI - Solvent effects on the kinetics of the interaction of 1-pyrenecarboxaldehyde with calf thymus DNA. AB - The kinetics of the interaction of a fluorescent probe, 1-pyrenecarboxaldehyde, with calf thymus DNA has been studied in different water/alcohol mixtures (ethanol, 2-propanol, and ter-butanol) at 25 degrees C, by using the stopped flow technique. The kinetic curves are biexponential and reveal the presence of two processes whose rates differ by about 1 order of magnitude on the time scale. The dependence of the reciprocal fast relaxation time on the DNA concentration is linear, whereas the concentration dependence of the reciprocal slow relaxation time tends to a plateau at high DNA concentrations. The simplest mechanism consistent with the kinetic results involves a simple two-step series mechanism reaction scheme. The first step corresponds to the formation of a precursor complex, (DNA/Py)(I), while the second one corresponds to full intercalation of the pyrene dye between the DNA base pairs. The values of the rate constants of both steps decrease as water activity decreases. The results have been discussed in terms of solvation of the species and changes in the viscosity of the solution. PMID- 20297773 TI - New salts of the waterstable P(2)Se(6)(4-) anion. AB - The structures of two new salts of the P(2)Se(6)(4-) anion, [(py(2)Li)](4)[P(2)Se(6)].2py and [pyH](4)[P(2)Se(6)].H(2)O, prepared using a new synthetic route in solution starting from easily available educts, are presented. The salts are characterized also in solution by means of multinuclear ((31)P, (77)Se, (7)Li) NMR spectroscopy. The (31)P and (77)Se NMR spectrum of the waterstable P(2)Se(6)(4-) anion are discussed in detail for the first time. The chemical shift of the P(2)Se(6)(4-) anion in the Li(+) salts depends strongly on the solvent used. Remarkably, the newly synthesized salts are stable in water. PMID- 20297774 TI - Facile synthesis of silver nanoparticles in CO2-expanded liquids from silver isostearate precursor. AB - This approach provides a new technique to synthesize silver nanoparticles (AgNPs) using CO(2)-expanded liquids (CXLs) as the processing medium. A soluble form of silver carboxylate, silver isostearate (AgISt), was synthesized and characterized. The XRD and DSC analyses indicated that the methylated branched alky chains in AgISt exhibited a steric hindrance to impede the growth of layered structure of AgISt molecules, which led to the high solubility of AgISt in nonpolar solvents. By using AgISt as silver precursor, AgNPs of 2.64 +/- 0.51 nm in diameter were synthesized in CO(2)-expanded heptane with H(2) as the reducing agent. The ATR-FTIR analysis showed that the produced AgNPs were capped with isostearic acid, which was derived from the reduction of AgISt. Hence, the isostearic acid capped AgNPs were well-dispersed in heptane to form a stable silver organosol. PMID- 20297775 TI - New method to determine surface area and its energy distribution for nonporous solids: a computer simulation and experimental study. AB - We present in this article a new method to determine the "geometrical" surface area of nonporous solids. This method is based on the total number of molecules dosed into the adsorption cell and a knowledge of the distribution of molecules between the gas phase and the surface phase. By matching this experimental amount with the corresponding theoretical equation, we can derive not only the surface area but also its energy distribution and the void volume of the adsorption cell. The method avoids the limitations of other methods presented in the literature. The BET method, for example, involves unrealistic assumptions and necessitates the choice of a molecular projection area. Our method does not suffer from these assumptions or limitations and is self-consistent, from the measurement of adsorption data to the final analysis of the surface area. The novelties of the method are the following: (i) it is valid over the complete range of reduced pressure, (ii) it does not require a molecular projection area, (iii) beside the total surface area, we also derive its energy distribution, and (iv) the helium expansion method (or any equivalent method) is not required to determine the void volume. PMID- 20297776 TI - Impact of sodium caseinate concentration and location on magnesium release from multiple W/O/W emulsions. AB - Water-in-oil-in-water (W/O/W) double emulsions were prepared and the rate of release of magnesium ions from the internal to the external aqueous phase was followed. Sodium caseinate was used not only as a hydrophilic surface-active species but also as a chelating agent able to bind magnesium ions. The release occurred without film rupturing (no coalescence). The kinetics of the release process depended on the location (in only one or in both aqueous compartments) and on the concentration of sodium caseinate. The rate of release increased with the concentration of sodium caseinate in the external phase and decreased when sodium caseinate was present in the inner droplets. The experiments were interpreted within the frame of a mean-field model based on diffusion, integrating the effect of ion binding. The data could be adequately fitted by considering a time-dependent permeation coefficient of the magnesium ions across the oil phase. Our results suggested that ion permeability was influenced by the state of the protein interfacial layers which itself depended on the extent of magnesium binding. PMID- 20297777 TI - Stability of the parallel layer during alkane spreading and the domain structures of the standing-up layer. AB - The spreading of liquid alkanes over surfaces plays an important role in applications such as lubrication, painting, and printing. To make significant advances in these fields, it is essential to increase our understanding of the interactions between alkanes and surfaces. Long-chain alkanes form two typical adsorption structures on a surface--the parallel phase and the standing-up phase. The most thermodynamically stable structure is the parallel phase, in which the alkane molecules lie flat on the surface. If the temperature is slightly below the bulk melting point, then alkanes form a thermodynamically stable standing-up phase on top of an existing parallel layer. At lower temperatures, the standing up phase becomes metastable. Using atomic force microscopy, we have found that the standing-up alkane layer consists of multiple domains, indicating that the standing-up layer forms through a multinucleation process during the liquid-solid transition on the surface. If, however, the temperature is above the melting point, then we have found that the standing-up layer shrinks to a droplet and leaves a residue on its original position. During the spreading of an alkane droplet, the parallel layer forms on the substrate surface surrounding the droplet by adsorption from the vapor, which precedes the arrival of the liquid. There has been uncertainty, however, as to whether the parallel layer moves with the liquid alkane or remains stationary during spreading. In this study, we used the residue left on the parallel layer as a landmark to monitor the movement of the parallel layer during the spreading of an alkane droplet. Using this landmark, we found that the parallel layer remained stationary on the substrate, indicating that the liquid alkane spreads on a stationary parallel layer surface. Therefore, this study reveals that the surface properties of the parallel layer- not the surface properties of the substrate--control the spreading and wetting of a liquid alkane. PMID- 20297778 TI - Phospholipid complexation of general anesthetics in fluid bilayers. AB - A nearest-neighbor recognition analysis has been performed in cholesterol-rich and cholesterol-poor liposomes derived from 1,2-dipalmitoyl-sn-glycero-3 phosphocholine (DPPC) in the presence of varying concentrations of chloroform. This analysis has yielded a fundamentally new, molecular-level view of the interaction of general anesthetics with lipid bilayers, which may be relevant to their biological action; that is, DPPC forms 1:1 complexes with CHCl(3) in both membranes in the fluid bilayer state. PMID- 20297779 TI - Atom probe microscopy of self-assembled monolayers: preliminary results. AB - We have achieved three-dimensional imaging of decanethiol self-assembled monolayers (SAMs) on metal surfaces by atom probe tomography (APT). The present Letter provides preliminary results on Ni [001] and Au [111], shows the analytical potential of APT analysis of SAMs, and details developments in specimen preparation and in data-treatment methodologies. Importantly, the investigation of the mass spectra from analysis of the SAMs revealed no combination of sulfur and hydrogen at the interface between the metal substrates and the organic materials, potentially providing insight about the bonding of the thiols on the substrate. PMID- 20297780 TI - P450cam visits an open conformation in the absence of substrate. AB - P450cam from Pseudomonas putida is the best characterized member of the vast family of cytochrome P450s, and it has long been believed to have a more rigid and closed active site relative to other P450s. Here we report X-ray structures of P450cam crystallized in the absence of substrate and at high and low [K(+)]. The camphor-free structures are observed in a distinct open conformation characterized by a water-filled channel created by the retraction of the F and G helices, disorder of the B' helix, and loss of the K(+) binding site. Crystallization in the presence of K(+) alone does not alter the open conformation, while crystallization with camphor alone is sufficient for closure of the channel. Soaking crystals of the open conformation in excess camphor does not promote camphor binding or closure, suggesting resistance to conformational change by the crystal lattice. This open conformation is remarkably similar to that seen upon binding large tethered substrates, showing that it is not the result of a perturbation by the ligand. Redissolved crystals of the open conformation are observed as a mixture of P420 and P450 forms, which is converted to the P450 form upon addition of camphor and K(+). These data reveal that P450cam can dynamically visit an open conformation that allows access to the deeply buried active site without being induced by substrate or ligand. PMID- 20297781 TI - Biological surface effects of metallic nanomaterials for applications in assembly and catalysis. AB - Recent experimental evidence has suggested that bioinspired techniques represent promising avenues toward the production of functional nanomaterials that possess a high degree of activity. These materials are prepared under synthetically simple and efficient conditions, thus making them attractive alternatives to many traditional methods that employ hazardous and harsh conditions. Many biomimetic methods employ peptide and amino acid binding events on the surfaces of nanostructures to generate materials that are stable in solution. The basis of both the stability and activity of these materials is likely to be controlled by the biotic/abiotic interface, which is mediated by the bioligand binding process. Unfortunately, most readily available techniques are unable to be used to study this intrinsic process; however, very recent studies have begun to shed light on this important event. In this feature article, an overview of the understanding of peptide and amino acid binding events to nanomaterials and how these motifs can be exploited for activities in nanoparticle assembly and catalytic reactivity is discussed. From both 2D surface studies and computational modeling analyses, different biomolecule binding characteristics have been elucidated. These results indicate that the amino acid sequence and peptide secondary structure play important roles in the binding capability. Furthermore, these studies suggest that the peptides are able to form specific patterns and motifs once bound to the nanoparticle surface. This attribute could affect the nanoparticle electronics and can play a significant role in their activities to generate functional materials. From these binding motifs, the ability of reagents to interact with the metallic surface is possible, thus affecting many of the properties of these materials. PMID- 20297782 TI - Polymerizable biomimetic vesicles with controlled local presentation of adhesive functional DOPA groups. AB - Inspired by strong adhesive properties of mussel footprint proteins, which are largely governed by the presence of dihydroxy-phenylalanine (DOPA) amino acid moieties, we present a novel approach for presenting DOPA groups in a very defined way in order to modulate the adhesion between artificial interfaces. To this end, linear peptide amphiphiles are synthesized with attached DOPA functional groups and a polymerizable diacetylenic tail. The obtained amphiphiles can be coassembled with matrix amphiphiles into vesicles, which can be subsequently stabilized through UV-light-induced solid-state polymerization. Depending on the molar ratio of matrix and adhesive amphiphiles, the vesicles self-assemble into spherical, fibrilar, or planar nanostructures. The adhesive properties of the surface-adsorbed vesicles are evaluated by drop casting them onto a planar solid substrate and performing macroscopic shear tests in contact with a similar substrate. The shear forces are investigated as a function of substrate chemistry, vesicle polymerization conditions, vesicle concentration, and number of adhesive DOPA groups in the interface. Substrate adhesion is enhanced by surface-confined vesicles and greatly depends on the presentation of DOPA groups in the adhesive interface, either as a mono- or multilayer conformation. Because the adhesive structures can be transferred onto substrates from low-viscosity aqueous solution, they may serve as interesting nanoscale gluing pads in future applications, where the high viscosity of polymer-based glues renders the controlled formation of nanoscale adhesion pads difficult. PMID- 20297783 TI - Neutral, ion gas-phase energetics and structural properties of hydroxybenzophenones. AB - We have carried out a study of the energetics, structural, and physical properties of o-, m-, and p-hydroxybenzophenone neutral molecules, C(13)H(10)O(2), and their corresponding anions. In particular, the standard enthalpies of formation in the gas phase at 298.15 K for all of these species were determined. A reliable experimental estimation of the enthalpy associated with intramolecular hydrogen bonding in chelated species was experimentally obtained. The gas-phase acidities (GA) of benzophenones, substituted phenols, and several aliphatic alcohols are compared with the corresponding aqueous acidities (pK(a)), covering a range of 278 kJ.mol(-1) in GA and 11.4 in pK(a). A computational study of the various species shed light on structural effects and further confirmed the self-consistency of the experimental results. PMID- 20297784 TI - DNA-mediated electron transfer in naphthalene-modified oligonucleotides. AB - Naphthalene-modified oligonucleotides have been synthesized and characterized with respect to electron transfer chemistry. Using the Sonogashira coupling reaction, naphthalene can be covalently anchored onto a modified uridine through an ethynyl linkage. This tethering allows for effective electronic coupling with the DNA bases, resulting in a significant red shift of the absorption bands of the naphthalenic chromophore. Modification with this chromophore does not appear to affect the overall stability and structure of the DNA. Upon selective irradiation of the naphthalene moiety at 340 nm, photoreduction of a distal electron trap, 5-bromouridine, embedded in the DNA base stack occurs. This DNA mediated reduction from a distance was found to be significantly more efficient with substitution of 5-bromouridine toward the 5'-end than toward the 3'-end. These results support a general preference for electron transfer through DNA toward the 5'-end, irrespective of the donor. In addition, differences in efficiency of photoreduction through intrastrand and interstrand pathways are observed. For DNA-mediated reduction, as with DNA-mediated oxidation, significant differences in the charge transfer reaction are apparent that depend upon subtle differences in coupling into the DNA base stack. PMID- 20297785 TI - Azide-tetrazole equilibrium of C-6 azidopurine nucleosides and their ligation reactions with alkynes. AB - Facile syntheses of C-6 azidopurine ribonucleosides and 2'-deoxyribonucleosides have been developed. For silyl- and acetyl-protected as well as unprotected nucleosides, access to the azido derivatives could be readily attained via displacement of BtO(-) from the O(6)-(benzotriazol-1-yl)inosine nucleosides by azide anion. Use of diphenylphosphoryl azide/DBU as a simple route to the acetyl protected azido nucleosides was also evaluated, but this proved to be inferior. Since these azido nucleosides can exist in an azide.tetrazole equilibrium, the effect of solvent polarity on this equilibrium was investigated. Subsequently, a detailed analysis of Cu-mediated azide-alkyne ("click") ligation was undertaken. Biphasic CH(2)Cl(2)/H(2)O medium proved to be best for the ligation reactions, suppressing the undesired azide reduction that was competing. Interestingly, although the tetrazolyl isomer predominates (ca. 80%) in CD(2)Cl(2) and in CD(2)Cl(2)/D(2)O, the Cu-catalyzed click reactions proceed smoothly with the silyl-protected ribo- and 2'-deoxyribonucleosides, leading to the C-6 triazolyl products in good to excellent yields. Thus, depletion of the azido form from the reaction mixture shifts the azide.tetrazole equilibrium, eventually resulting in complete consumption of azide and tetrazole. In several cases, major and minor azide-alkyne ligation products were observed, and characterization data are provided for both. In order to confirm the regiochemistry leading to the major isomer, one product was crystallized and evaluated by X-ray crystallography. The Cu-catalyzed azide-alkyne ligation is clearly efficient and significantly superior to thermal reactions, which were slow. Biological evaluation showed low cytotoxicities for the agents, suggesting their usefulness as biological probes. PMID- 20297787 TI - The effects of alpha-helical structure and cyanylated cysteine on each other. AB - Beta-thiocyanatoalanine, or cyanylated cysteine, is an artificial amino acid that can be introduced at solvent-exposed cysteine residues in proteins via chemical modification. Its facile post-translational synthesis means that it may find broad use in large protein systems as a probe of site-specific structure and dynamics. The C[triple bond]N stretching vibration of this artificial side chain provides an isolated infrared chromophore. To test both the perturbative effect of this side chain on local secondary structure and its sensitivity to structural changes, three variants of a model water-soluble alanine-repeat helix were synthesized containing cyanylated cysteine at different sites. The cyanylated cysteine side chain is shown to destabilize, but not completely disrupt, the helical structure of the folded peptide when substituted for alanine. In addition, the [triple bond]N stretching bandwidth of the artificial side chain is sensitive to the helix-coil structural transition. These model system results indicate that cyanylated cysteine can be placed into protein sequences with a native helical propensity without destroying the helix, and further that the CN probe may be able to report local helix formation events even when it is water exposed in both the ordered and disordered conformational states. These results indicate that cyanylated cysteine could be a widely useful probe of structure forming events in proteins with large in vitro structural distributions. PMID- 20297789 TI - Graphene oxide as a matrix for enzyme immobilization. AB - Graphene oxide (GO), having a large specific surface area and abundant functional groups, provides an ideal substrate for study enzyme immobilization. We demonstrated that the enzyme immobilization on the GO sheets could take place readily without using any cross-linking reagents and additional surface modification. The atomically flat surface enabled us to observe the immobilized enzyme in the native state directly using atomic force microscopy (AFM). Combining the AFM imaging results of the immobilized enzyme molecules and their catalytic activity, we illustrated that the conformation of the immobilized enzyme is mainly determined by interactions of enzyme molecules with the functional groups of GO. PMID- 20297790 TI - Facile C-H alkylation in water: enabling defect-free materials for optoelectronic devices. AB - A facile method for the alkylation of fluorene achieved via direct C-H alkylation under aqueous conditions is reported, wherein the formation of fluorenone is inhibited, resulting in the exclusive formation of the desired dialkyl substituted fluorene monomer. As a proof of concept, this method has also been successfully extended to perform N-alkylation of carbazole, diphenylamine, and N,N-dialkylation of aniline in high yields. PMID- 20297791 TI - A prochelator activated by beta-secretase inhibits Abeta aggregation and suppresses copper-induced reactive oxygen species formation. AB - The intersection of the amyloid cascade hypothesis and the implication of metal ions in Alzheimer's disease progression has sparked an interest in using metal binding compounds as potential therapeutic agents. In the present work, we describe a prochelator SWH that is enzymatically activated by beta-secretase to produce a high affinity copper chelator CP. Because beta-secretase is responsible for the amyloidogenic processing of the amyloid precursor protein, this prochelator strategy imparts disease specificity toward copper chelation not possible with general metal chelators. Furthermore, once activated, CP efficiently sequesters copper from amyloid-beta, prevents and disassembles copper induced amyloid-beta aggregation, and diminishes copper-promoted reactive oxygen species formation. PMID- 20297794 TI - Water and trehalose: how much do they interact with each other? AB - The observation made by early naturalists that some organisms could tolerate extreme environmental condisions and "enjoy the advantage of real resurrection after death" [ Spallanzani , M. Opuscules de Physique Animale et Vegetale 1776 (translated from Italian by Senebier , J. Opuscules de Physique Animale et Vegetale 1787 , 2 , 203 - 285 )] stimulated research that still continues to this day. Cryptobiosis, the ability of an organism to tolerate adverse environments, such as dehydration and low temperatures, still represents an unsolved and fascinating problem. It has been shown that many sugars play an important role as bioprotectant agents, and among the best performers is the disaccharide trehalose. The current hypothesis links the efficiency of its protective role to strong modifications of the tetrahedral arrangement of water molecules in the sugar hydration shell, with trehalose forming many hydrogen bonds with the solvent. Here, we show, by means of state-of-the-art neutron diffraction experiments combined with EPSR simulations, that trehalose solvation induces very minor modifications of the water structure. Moreover, the number of water molecules hydrogen-bonded to the sugar is surprisingly small. PMID- 20297792 TI - Investigation of the inclusions of puerarin and daidzin with beta-cyclodextrin by molecular dynamics simulation. AB - Puerarin and daidzin, two major isoflavonoids of Radix puerariae , are widely adopted in traditional Chinese medicine. Foundational aspects related to separating the two compounds are essential to develop a more economical purification process. Inclusion models of the two compounds with beta cyclodextrin (beta-CD) have been investigated by molecular dynamics simulation. Computational results reveal that both puerarin and daidzin can induce a conformational change of beta-CD, which is compressed in one direction and stretched in the other. The effect of solvent and media on the conformational change of beta-CD and the movement of guest molecules inside the cavity has been investigated. Furthermore, hydrogen bonding interactions have been analyzed, and the results have been utilized for the explanation of separating puerarin from daidzin. PMID- 20297795 TI - Electrochemiluminescence biobarcode method based on cysteamine--gold nanoparticle conjugates. AB - The recently developed DNA-gold nanoparticle (DNA-GNP) biobarcode assay provides polymerase chain reaction (PCR)-like sensitivity for nucleic acid and protein targets without a need for enzymatic amplification. However, application of the conventional assay is challenged by its complex, expensive, time-consuming, and labor-intense procedure. Herein, we present a new electrochemiluminescence (ECL) biobarcode method based on cysteamine-GNP conjugates. In this strategy, an ECL nanoprobe is fabricated that relies on GNP that is modified with tris-(2,2' bipyridyl) ruthenium (TBR) labeled cysteamine to boost ECL signals and single strand DNA for target recognition. Specifically, a sandwich complex that consists of a biotin labeled capture probe, target DNA, and cysteamine-GNP conjugate is captured by magnetic microparticles (MMPs) and subsequently identified by the ECL signals from loaded TBR. With the use of the developed probe, a limit of detection as low as 100 fM can be achieved and the assay exhibits excellent selectivity for single-mismatched DNA detection even in human serum. The proposed ECL based method should have wide applications in diagnosis of genetic diseases due to its high sensitivity, simplicity, and low cost. PMID- 20297796 TI - Unusual metal-coordinated zwitterionic P-C-N-C-N-C phosphido adducts. AB - Rare examples of homodinuclear zwitterionic Pd(II) and Pt(II) complexes with bridging, two-coordinate P{cyclo-CH(2)N(R)CHN(R)CH(2)} ligands (R = 4 FC(6)H(4)CH(2), C(6)H(5)CH(2)) have been characterized by single-crystal X-ray diffraction using synchrotron radiation. Short N-C distances and enlarged N-C-N bond angles support electron delocalization in the central N-C-N backbone. PMID- 20297797 TI - Concave plasmonic particles: broad-band geometrical tunability in the near infrared. AB - Optical resonances spanning the near-infrared spectrum (1-2 microm) were exhibited experimentally by arrays of plasmonic nanoparticles with concave cross section. The concavity of the particle was shown to be the key component for enabling the broad band tunability of the resonance frequency, even for particles with dimensional aspect ratios of order unity. The atypical flexibility of setting the resonance wavelength is shown to stem from a unique interplay of local geometry with surface charge distributions. PMID- 20297798 TI - A novel synthesis of oxabicyclo[3.3.1]nonanone via (3,5)-oxonium-ene reaction. AB - Oxabicyclo[3.3.1]nonanone can conveniently be prepared by the reaction of trans-p menth-6-ene-2,8-diol and aldehyde or epoxide mediated by boron trifluoride etherate in good yields. The reaction proceeds via (3,5)-oxonium-ene-type reaction. PMID- 20297799 TI - Cyclam-based "clickates": homogeneous and heterogeneous fluorescent sensors for Zn(II). AB - In an effort to improve upon the recently reported cyclam based zinc sensor 1, the "click"-generated 1,8-disubstituted analogue 2 has been prepared. The ligand shows a 2-fold increase in its fluorescence emission compared to 1 exclusively in the presence of Zn(II) that is typical of switch-on PET fluorescent sensors. Single crystal X-ray diffraction of complexes of model ligand 10 reveals that the configuration adopted by the macrocyclic framework is extremely sensitive to the metal ion to which it coordinates. For Zn(II), Mg(II), and Li(I) the metal ions adopt an octahedral geometry with a trans III configuration of the cyclam ring. In contrast for Ni(II) the ligand adopts the rare cis V configuration, while for Cu(II) a clear preference for five-coordinate geometry is displayed with a trans I configuration of the macrocyclic ring being observed in two essentially isostructural compounds prepared via different routes. The ligand displays an increased selectivity for Zn(II) compared to 1 in the majority of cases with excellent selectivity upheld over Na(I), Mg(II), Ca(II), Mn(II), Ni(II), Co(II), and Fe(III). In contrast for Cu(II) and Hg(II) little improvement was observed for 2 compared to 1 and for Cd(II) the selectivity of the new ligand was inferior. In the light of these findings and the slower response times for ligand 2, our original "click"-generated cyclam sensor system 1 was employed in a proof of concept study to prepare a heterogeneous sol-gel based material which retains its PET response to Zn(II). The versatile nature of the sol-gel process importantly allows the simple preparation of a variety of nanostructured materials displaying high surface area-volume ratio using fabrication methods such as soft lithography, electrospinning, and nanopipetting. PMID- 20297800 TI - A unified total synthesis of aspergillides A and B. AB - An enantioselective total synthesis of aspergillides A and B has been accomplished based on a unified strategy, wherein a hydroxy-directed, highly chemoselective olefin cross-metathesis and a diastereoselective intramolecular oxa-conjugate cyclization were employed to forge the 2,6-substituted tetrahydropyran substructure. PMID- 20297801 TI - Polychlorinated biphenyls PCB 52, PCB 180, and PCB 138 impair the glutamate nitric oxide-cGMP pathway in cerebellar neurons in culture by different mechanisms. AB - Polychlorinated biphenyls (PCBs) are persistent organic pollutants that accumulate in the food chain and are present in human blood and milk. Children born to mothers exposed to PCBs show cognitive deficits, which are reproduced in rats perinatally exposed to PCBs. It has been proposed that PCB-induced cognitive impairment is due to impairment of the glutamate-nitric oxide (NO)-cGMP pathway. The aim of the present work was to assess whether chronic exposure to the nondioxin-like PCB52, PCB138, or PCB180 alters the function of this pathway in primary cultures of rat cerebellar neurons and to assess whether different PCBs have similar or different mechanisms of action. PCB180 and PCB138 impair the function of the glutamate-NO-cGMP pathway at nanomolar concentrations, and PCB52 impairs the function of the glutamate-NO-cGMP pathway at micromolar concentrations. The mechanisms by which different PCBs impair the function of the glutamate-NO-cGMP pathway are different. Each PCB affects the pathway at more than one step but with different potency and, for some steps, in opposite ways. Exposure to the PCBs alters the basal concentrations of intracellular calcium, NO, and cGMP. The three PCBs increase NO; however, PCB52 and PCB138 increase basal cGMP, while PCB180 decreases it. PCB52 and PCB138 decrease the activation of soluble guanylate cyclase by NO, and PCB180 increases it. Long-term exposure to PCB52, PCB180, or PCB138 reduces the activation of NO synthase and the whole glutamate-NO-cGMP pathway in response to activation of N-methyl-d-aspartate receptors. The EC(50) was 300 nM for PCB52 and 2 nM for PCB138 or PCB180. These results show that chronic exposure to nondioxin like PCBs impairs the function of the glutamate-NO-cGMP pathway in cerebellar neurons by different mechanisms and with different potencies. Impaired function of this pathway would contribute to the cognitive alterations induced by perinatal exposure to PCBs in humans. PMID- 20297803 TI - Investigation of bioactivation of ticlopidine using linear ion trap/orbitrap mass spectrometry and an improved mass defect filtering technique. AB - The bioactivation of ticlopidine, a widely used antiplatelet drug, into reactive metabolites and their subsequent covalent binding to cellular macromolecules are thought to be involved in the occurrence of idiosyncratic hepatotoxicity in patients. In the present study, GSH/stable isotope-labeled GSH was used as the trapping agent to investigate the bioactivation pathways of ticlopidine in rat liver microsomes. The samples were analyzed by high-resolution linear ion trap/Orbitrap followed by multiple mass defect filtering (MDF). In total, 17 GSH adducts were detected, and a comprehensive profile for ticlopidine bioactivation has been proposed. The results show that ticlopidine can be directly bioactivated by rat P450s, forming GSH adducts through two major bioactivation pathways, thiophene-S-oxidation and thiophene epoxidation. These adducts were also formed substantially in human liver microsomes. Moreover, ticlopidine can be metabolized via multiple pathways before giving rise to reactive intermediates. The GSH adducts derived from epoxidation of the chlorophenyl moiety of ticlopide and bioactivation of N-dealkylated metabolites are reported here for the first time. The formation of a number of ticlopidine GSH adducts from diversified metabolic pathways mediated by P450s implies a high potential for protein binding and provides a conceivable link between the high reactivity of ticlopidine after bioactivation and the ticlopidine-induced toxicity. Additionally, the current approach has the following advantages as compared to previous high-resolution LC/MS methodologies. First, novel MDF utilized doubly charged ions as filter templates to detect the GSH adducts, mainly doubly charged in the ion source, resulting in broader detection coverage. Second, multiple mass defect filter templates were for the first time applied to reveal different classes of GSH adducts. Finally, a quick check of isotopic doublets and full examination of isotope fingerprints in the accurate mass were introduced to screen out false positives and enhance the identification of low abundant GSH adducts. PMID- 20297804 TI - Interaction between poly(acrylic acid) and phospholipid vesicles: effect of pH, concentration, and molecular weight. AB - Interactions between phospholipid vesicles and poly(acrylic acid) (PAA) are of fundamental importance for pH-sensitive delivery systems in pharmaceutical applications. In this study, we investigated the behavior of 1,2-dipalmitoyl-sn glycero-3-phosphocholine (DPPC) at varied concentrations of PAA with low and high molecular weights. Differential scanning calorimetry and fluorescence microscopy experiments suggested that hydrogen bonding between the carboxyl group of PAA and the phosphodiester group of the lipid is the main driving force for association under acidic conditions. Complexation between DPPC and PAA depends on the PAA molecular weight and concentration. At high enough concentrations of the large molecular weight PAA, the polymer can completely disrupt the bilayers of DPPC. For the small molecular weight PAA, in contrast, the complexation leads to vesicle aggregation without destroying the bilayers. The difference in complex structure was detected by SEM and a UV-visible spectrophotometer. At alkaline pH, complexation did not occur because of strong dissociation of PAA. PMID- 20297807 TI - Porphyrin on a half-shell! Synthesis and characterization of corannulenoporphyrins. AB - An efficient synthetic method for preparing corannulenoporphyrins is described. Nitrocorannulene was reacted with ethyl isocyanoacetate in the presence of a phosphazene base to generate the pivotal corannulenopyrrole intermediate. Following cleavage of the ethyl ester moiety with KOH in ethylene glycol at 180 190 degrees C, the heptacyclic system was reacted with acetoxymethylpyrroles under mildly acidic conditions to afford tripyrranes. The proton NMR spectra for these tripyrrolic intermediates suggest that they can take on helical geometries, but the conformations are dependent on the nature of the terminal ester groupings and may be altered by solvent interactions. Treatment of a di-tert-butyl ester tripyrrane with TFA cleaved the protective groups, and subsequent condensation with diformylpyrroles in TFA-CH(2)Cl(2), followed by oxidation with DDQ or ferric chloride, gave excellent yields of corannulenoporphyrins. Nickel(II), copper(II), and zinc complexes of this system were also prepared, and the nickel derivative was also further characterized by X-ray crystallography. The same synthetic strategy was also used to prepare a porphyrin with fused acenaphthylene and corannulene subunits. The fused bowl-shaped corannulene provides these porphyrins with a unique structural component that increases solubility by reducing pi-pi stacking interactions. PMID- 20297806 TI - One-step conversion of azine N-oxides to alpha-1,2,4-triazolo-, 1,2,3-triazolo, imidazolo-, and pyrazoloheteroarenes. AB - Pyridine, quinoline, isoquinoline, azaindole, and pyrimidine N-oxides were converted to their alpha-triazole and alpha-diazole derivatives by treatment with the corresponding p-toluenesulfonylazoles and Hunig's base at elevated temperatures. PMID- 20297805 TI - Use of glucuronidation fingerprinting to describe and predict mono- and dihydroxyflavone metabolism by recombinant UGT isoforms and human intestinal and liver microsomes. AB - The present study aims to predict the regiospecific glucuronidation of three dihydroxyflavones and seven monohydroxyflavones in human liver and intestinal microsomes using recombinant UGT isoforms. Seven monohydroxyflavones (or HFs), 2' , 3'-, 4'-, 3-, 5-, 6-, and 7-hydroxyflavone, and three dihydroxyflavones (or diHFs), 3,7-dihydroxyflavone (3,7-diHF), 3,5-dihydroxyflavone (3,5-diHF), and 3,4'-dihydroxyflavone (3,4'-diHF), were chosen, and rates were measured at 2.5, 10, and 35 microM. The results indicated that the position of glucuronidation of three diHFs could be determined by using the UV spectra of relevant HFs. The results also indicated that UGT1A1, UGT1A7, UGT1A8, UGT1A9, UGT1A10 and UGT2B7 are the most important six UGT isoforms for metabolizing the chosen flavones. Regardless of isoforms used, 3-HF was always metabolized the fastest whereas 5-HF was usually metabolized the slowest, probably due to the formation of an intramolecular hydrogen bond between 4-carbonyl and 5-OH group. Relevant UGT isoform-specific metabolism rates generally correlated well with the rates of glucuronidation in human intestinal and liver microsomes at each of the three tested concentrations. In conclusion, the glucuronidation "fingerprint" of seven selected monohydroxyflavones was affected by UGT isoforms used, positions of the OH group, and the substrate concentrations, and the rates of glucuronidation by important recombinant UGTs correlated well with those obtained using human liver and intestinal microsomes. PMID- 20297808 TI - Multiple nanowire species synthesized on a single chip by selectively addressable horizontal nanochannels. AB - The synthesis of horizontal porous anodic alumina (PAA) structures with individually addressable channel systems is demonstrated. This was achieved by developing a multicontact design of aluminum finger structures (two to five contacts) on silicon wafers. These aluminum contacts were electrically isolated from each other, allowing the individual anodization of each contact at different conditions. This way it is possible to synthesize different pore diameters, pore densities, and channel lengths on a single chip. Scanning electron microscopy (SEM) characterization revealed that the neighboring contacts are not significantly altered during the anodization procedure. After successful barrier layer thinning, the individual finger structures of each contact were filled by electrodeposition and thermal chemical vapor deposition. The resulting metal (Au, Cu, Ni, Co) and semiconductor (Te, Si) nanowires embedded within the porous anodic alumina mold were characterized by SEM and energy dispersive X-ray measurements. The multicontact fabrication results open a new route toward complex nanoelectronic and sensing applications. PMID- 20297809 TI - The solution structure of (+)-spongistatin 1 in DMSO. AB - The solution structure of (+)-spongistatin 1 (1) has been determined via 1- and 2 D NMR techniques in conjunction with extensive in silico conformational analysis to comprise a mixture of 4 major rapidly interconverting conformational families. PMID- 20297811 TI - Climate variability and temporal trends of persistent organic pollutants in the arctic: a study of glaucous gulls. AB - The impact of climate variability on temporal trends (1997-2006) of persistent organic pollutants (POPs; polychlorinated biphenyls [PCB], hexachlorobenzene [HCB], and oxychlordane) was assessed in glaucous gulls (Larus hyperboreus) breeding in the Norwegian Arctic (n = 240). The Arctic Oscillation (AO: an index of sea-level pressure variability in the Northern Hemisphere above 20 degrees N) with different time lags was used as a climate proxy. The estimated concentrations of POPs in glaucous gull blood/plasma declined substantially (16 60%) over the time period. Multiple regression analyses showed that the rates of decline for POPs were correlated to climate variation when controlling for potential confounding variables (sex and body condition). More specifically AO in the current winter showed negative associations with POP concentrations, whereas the relationships with AO measurements from the year preceding POP measurements (AO preceding summer and AO preceding winter) were positive. Hence, gulls had relatively higher POP concentrations in breeding seasons following years with high air transport toward the Arctic. Furthermore, the impact of AO appeared to be stronger for HCB, a relatively volatile compound with high transport potential, compared to heavy chlorinated PCB congeners. This study thus suggests that predicted climate change should be considered in assessments of future temporal trends of POPs in Arctic wildlife. PMID- 20297810 TI - Design, synthesis, and biological evaluation of EF- and ABEF- analogues of (+) spongistatin 1. AB - The design, synthesis, and biological evaluation of two potential (+) spongistatin 1 analogues have been achieved. The analogues, incorporating tethers (red) in place of the ABCD and the CD components of the (+)-spongistatin 1 macrolide, were designed such that the conformations of the retained skeleton (blue) would mimic the assigned major solution conformation of the natural product The nanomolar cytotoxicity observed for the ABEF analogue provides strong support for the assigned solution conformation. PMID- 20297812 TI - Mercury contamination in fish in midcontinent great rivers of the United States: importance of species traits and environmental factors. AB - We measured mercury (Hg) concentrations in whole fish from the Upper Mississippi, Missouri, and Ohio Rivers to characterize the extent and magnitude of Hg contamination and to identify environmental factors influencing Hg accumulation. Concentrations were generally lower (80% of values between 20-200 ng g(-1) wet weight) than those reported for other regions (e.g., upper Midwest and Northeast U.S.). Mercury exceeded the risk threshold for belted kingfisher (Ceryle alcyon, the most sensitive species considered) in 33-75% of river length and 1-7% of river length for humans. Concentrations were lower in the Missouri than in the Mississippi and Ohio Rivers, consistent with continental-scale patterns in atmospheric Hg deposition. Body size and trophic guild were the best predictors of Hg concentrations, which were highest in large-bodied top predators. Site geochemical and landscape properties were weakly related with fish Hg. Moreover, relationships often ran contrary to conventional wisdom, and the slopes of the relationships (positive or negative) were inconsistent among fish guilds and rivers. For example, sulfate is positively associated with fish Hg concentrations but was negatively correlated with Hg in five of six regression models of tissue concentrations. Variables such as pH, acid neutralizing capacity, and total phosphorus did not occur at levels associated with high fish Hg concentrations, partially explaining the relatively low Hg values we observed. PMID- 20297813 TI - Directing the oligomer size distribution of peroxidase-mediated cross-linked bovine alpha-lactalbumin. AB - Enzymatic protein cross-linking is a powerful tool to change protein functionality. For optimal functionality in gel formation, the size of the cross linked proteins needs to be controlled, prior to heating. In the current study, we addressed the optimization of the horseradish peroxidase-mediated cross linking of calcium-depleted bovine alpha-lactalbumin. To characterize the formed products, the molecular weight distribution of the cross-linked protein was determined by size exclusion chromatography. At low ionic strength, more dimers of alpha-lactalbumin are formed than at high ionic strength, while the same conversion of monomers is observed. Similarly, at pH 5.9 more higher oligomers are formed than at pH 6.8. This is proposed to be caused by local changes in apo alpha-lactalbumin conformation as indicated by circular dichroism spectroscopy. A gradual supply of hydrogen peroxide improves the yield of cross-linked products and increases the proportion of higher oligomers. In conclusion, this study shows that the size distribution of peroxidase-mediated cross-linked alpha-lactalbumin can be directed toward the protein oligomers desired. PMID- 20297814 TI - Development of a Mab-based heterologous immunoassay for the broad-selective determination of organophosphorus pesticides. AB - A broad-selective monoclonal antibody (Mab) for organophosphorus (OP) pesticides was raised using heterologous indirect enzyme-linked immunosorbent assay (ELISA) to screen hybridomas. On the basis of this Mab, five coating antigens were used to develop homologous and heterologous indirect competitive ELISAs. With the most suitable competitor, a sensitive and broad-selective ELISA was developed. The IC(50) values were estimated to be 20.32 ng/mL for parathion, 21.44 ng/mL for methyl-parathion, 42.15 ng/mL for fenitrothion, and 58.85 ng/mL for isocarbophos. Spike recoveries were between 70.52 and 103.27% for the detection of single pesticide residues of the four OP pesticides in purple-clayed paddy soil. Moreover, the chosen ELISA was then applied to the detection of mixtures of parathion and methyl-parathion in soil samples. The average recovery and coefficient of variation were 80.91 and 4.82%, respectively. Results proved that this broad-selective ELISA would be useful for the multiresidue determination of OP pesticides. PMID- 20297815 TI - Simultaneous screening of herbicide degradation byproducts in water treatment plants using high performance liquid chromatography-tandem mass spectrometry. AB - Currently, herbicides are widely used in various combinations at many stages of cultivation and during postharvest storage. There are increasing concerns about the public health impact of herbicide degradation byproducts that may be present in water bodies used either as drinking water or for recreational purposes. This work investigated the sulfonic acid and oxanilic acid degradation products of metolachlor, alachlor, acetochlor, and propachlor in a variety of water bodies. The objective was to develop a fast, accurate, and easy method for quantitative analysis of herbicide degradation products using liquid chromatography with tandem mass spectrometry without solid phase extraction, but performing levels of detection lower than those obtained in previous studies with solid phase extraction. This research also screened 68 water samples, both untreated source water and treated water, from 34 water treatment plants in Missouri. Finally, it examined seasonal trends in levels of those degradation products by collecting and testing samples monthly. This highly sensitive method can analyze these degradation products to low ng/L levels. The method limit of quantification ranges from 0.04 to 0.05 ppb for each analyte; and quantitative analyses show a precision with RSDs of around 0.6% to 3% in treated water and 2% to 19% in untreated source water. Concentrations of alachlor ESA, acetochlor OA, metolachlor OA, and metolachlor ESA were detected from the Missouri River and the Mississippi River water bodies in summer time. Occurrences of these compounds in treated water samples are all lower than those in the untreated source water samples. PMID- 20297816 TI - Ricinoleic acid as a marker for ergot impurities in rye and rye products. AB - Ergot alkaloid and ricinoleic acid contents of 63 ergot sclerotia samples from rye throughout Germany of the harvest years 2006-2009 were determined. Alkaloid contents were analyzed by means of high-performance liquid chromatography with fluorescence detection (HPLC-FLD) and ricinoleic acid contents by means of gas chromatography with flame ionization detection (GC-FID). Ergot alkaloid amounts ranged from 0.01 to 0.2 g/100 g of sclerotia with an average amount of 0.08 g/100 g. Ergotamine and ergocristine were identified as lead alkaloids representing 57% (w/w) of the total alkaloid content. The average ricinoleic acid amount in the ergot sclerotia was 10.3 g/100 g. Because of the low variation of ricinoleic acid content in the ergot sclerotia, a new method for the determination of ricinoleic acid in rye products as a marker for ergot contaminations was developed. This method allows the determination of ergot impurities as low as 0.01% (w/w). Furthermore, 29 rye products (flours, bread mix, bread) were investigated for their ricinoleic acid and ergot alkaloid contents. PMID- 20297817 TI - Combined chemical-biological treatment for prevention/rehabilitation of clogged wells by an iron-oxidizing bacterium. AB - Groundwater wells containing large concentrations of ferrous iron face serious clogging problems as a result of biotic iron oxidation. Following a short time after their start off, wells get clogged, and their production efficiency drop significantly up to a total obstruction, making cleanup and rehabilitation an economic burden. The present study was undertaken to test an experimental combined treatment (chemical and biological) for future prevention or rehabilitation of clogged wells. Sphaerotilus natans (an iron-oxidizing bacterium) freshly isolated from a deep well was grown to form biofilms on two systems: coupons and sand buried miniature wedge wire screen baskets. A combined chemical-biological treatment, applied at laboratory scale by use of glycolic acid (2%) and isolated bacteriophages against Sphaerotilus natans (SN1 and ER1-a newly isolated phage) at low multiplicity of infection (MOI), showed inhibition of biofilm formation and inactivation of the contaminant bacteria. In addition to complete inactivation of S. natans planktonic bacteria by the respective phages, earlier biofilm treatment with reduced glycolic acid concentration revealed efficient exopolysaccharide (EPS) digestion allowing phages to be increasingly efficient against biofilm matrix bacteria. Utilization of this combined treatment revealed clean surfaces of a model stainless steel wedge wire screen baskets (commonly used in wells) for up to 60 days. PMID- 20297818 TI - Structurally ordered FePt nanoparticles and their enhanced catalysis for oxygen reduction reaction. AB - We report the structure-controlled synthesis of FePt/MgO NPs and their catalysis for oxygen reduction reaction (ORR) in 0.5 M H(2)SO(4) solution. The synthesis yields fcc-FePt/MgO and fct-FePt/MgO NPs with the MgO coating being readily removed for catalytic studies. The fct-FePt NPs show higher activity and durability than the fcc-FePt in the ORR condition. The results indicate that the fully ordered fct-FePt could serve as a practical Pt-based catalyst for fuel cell applications. PMID- 20297820 TI - Selective manipulation of ICT and PET Processes in styryl-Bodipy derivatives: applications in molecular logic and fluorescence sensing of metal ions. AB - Remarkably versatile chemistry of Bodipy dyes allows the design and straightforward synthesis of multivalent-multitopic derivatives, which, with judicious selection of metal ion-ligand pairs based on known affinities, affords control and manipulation of photoinduced electron transfer and internal charge transfer processes as desired. We have demonstrated that metal ions acting as modulators (or inputs, in digital design parlance) can generate absorbance changes in accordance with the operation of a half-adder. In addition, an AND logic gate in the emission mode was delivered using a different binucleating arrangement of ligands. A molecular equivalent of a three-input AND logic gate was also obtained exploiting differential binding affinities of metal ions for different ligands. The results suggest that different metal ions can be used as nonannihilating inputs, selectively targeting various ligands incorporated within a single fluorophore, and with careful design, diverse photophysical processes can be selectively modulated, resulting in a range of signals, useful in molecular logic design, and offering an enticing potential for multianalyte chemosensors. PMID- 20297819 TI - High-mobility semiconducting naphthodithiophene copolymers. AB - We have designed and synthesized novel semiconducting polymers by introducing naphtho[1,2-b:5,6-b']dithiophene (NDT) into the polythiophene backbone. These polymers, which have a highly pi-extended heteroarene unit, achieved mobilities (>0.5 cm(2) V(-1) s(-1)) that are among the highest recorded to date for semiconducting polymers and most probably result from the highly ordered thin film structures with crystalline close pi stacking. It is noteworthy that the choice of isomeric heteroarenes in the unit can dramatically change the physical and electronic structures and hence the OFET performance of the semiconducting polymers, even though the two isomers possess similar electronic structures; interestingly, this contrasts with the trend in small-molecule systems. We believe that these findings will give new insight into the design of new organic semiconducting materials and that the present polymers are promising materials for printable electronics. PMID- 20297821 TI - Isolation of individual boron nitride nanotubes via peptide wrapping. AB - The isolation of individual boron nitride nanotubes (BNNTs) in aqueous phases has been achieved for the first time from raw materials based on the combination of peptide wrapping with a sonication procedure. Atomic force microscopic observations revealed the representative height and length of individual BNNTs. Fluorescence and infrared absorption spectra suggested the strong pi-pi interactions between BNNTs and the peptide. The absorption maxima of BNNTs were significantly blue-shifted from 200 nm for the original BNNTs to 193 nm. The modulation of the BNNT band gap with peptide wrapping promises potential applications of the peptide/BNNT complexes to various nanotechnologies. PMID- 20297822 TI - The productive merger of iodonium salts and organocatalysis: a non-photolytic approach to the enantioselective alpha-trifluoromethylation of aldehydes. AB - An enantioselective organocatalytic alpha-trifluoromethylation of aldehydes has been accomplished using a commercially available, electrophilic trifluoromethyl source. The merging of Lewis acid and organocatalysis provides a new strategy for the enantioselective construction of trifluoromethyl stereogenicity, an important chiral synthon for pharmaceutical, materials, and agrochemical applications. This mild and operationally simple protocol allows rapid access to enantioenriched alpha-trifluoromethylated aldehydes through a nonphotolytic pathway. PMID- 20297823 TI - Nucleophilic acyl substitution via aromatic cation activation of carboxylic acids: rapid generation of acid chlorides under mild conditions. AB - The first example of aromatic cation-activated nucleophilic acyl substitution has been achieved. The conversion of carboxylic acids to their corresponding acid chlorides occurs rapidly in the presence of 3,3-dichlorocyclopropenes via the intermediacy of cyclopropenium carboxylate complexes. The effect of cyclopropene substituents on the rate of conversion is examined. The addition of tertiary amine base is found to dramatically accelerate reaction, and conditions were developed for the preparation of acid sensitive acid chlorides. Preparative scale peptide couplings of two N-Boc amino acids were achieved with this method. PMID- 20297824 TI - NXO building blocks for backbone modification of peptides and preparation of pseudopeptides. AB - The design and synthesis of novel building blocks for peptide modification, termed "NXO", is reported. We describe the utility of these building blocks to prepare new pseudo- and oligopeptides and demonstrate the efficient assembly of modified tripeptides using both conventional liquid phase peptide synthesis and solid supported synthesis. Pertaining to the study of NXO in peptide mimicry, the structure of NXO-incorporating tripeptide beta-strand mimics was investigated in the N(L)AlaO incorporating beta-sheet model compound 13. Evidenced by spectroscopy and computation, 13 selectively adopts a beta-structure in chloroform and characteristically samples the NXO-modified backbone site in the core beta-sheet region. ROESY (HNMR) and molecular dynamics data suggest that when disrupting the cross-strand hydrogen-bonding pattern by switching the solvent from CDCl(3) to d(3)-MeOH, the main conformation with peptide and NXO peptide backbones similar to that in root mean square deviation of corresponding backbone atoms (rmsd) is preserved. PMID- 20297825 TI - Diarylheptanoid from Pleuranthodium racemigerum with in vitro prostaglandin E(2) inhibitory and cytotoxic activity. AB - Bioactivity-guided fractionation of an ethanolic extract of the rhizome of Pleuranthodium racemigerum, a tropical Zingiberaceae species from Northeastern Australia, resulted in the isolation and structural elucidation of 1-(4'' methoxyphenyl)-7-(4'-hydroxyphenyl)-(E)-hept-2-ene (1), a new diarylheptanoid related to curcumin. Compound 1 was a fairly potent inhibitor of prostaglandin E(2) production in 3T3 murine fibroblasts (IC(50) approximately 34 microM) and also displayed moderate cytotoxicity against this cell line (IC(50) = 52.8 microM). The compound also demonstrated cytotoxic activity against the P388D1 murine lymphoblast cell line (IC(50) = 117.0 microM) and four human cell lines: Caco-2 colonic adenocarcinoma (IC(50) = 44.8 microM), PC3 prostate adenocarcinoma (IC(50) = 23.6 microM), HepG2 hepatocyte carcinoma (IC(50) = 40.6 microM), and MCF7 mammary adenocarcinoma (IC(50) = 56.9 microM). The cytotoxicity of compound 1 closely resembled that of curcumin, in terms of both IC(50) values and dose response curves. PMID- 20297826 TI - Enzymatic kinetic resolution of silybin diastereoisomers. AB - In nature, the flavonolignan silybin (1) occurs as a mixture of two diastereomers, silybin A and silybin B, which in a number of biological assays exhibit different activities. A library of hydrolases (lipases, esterases, and proteases) was tested for separating the silybin A and B diastereomers by selective transesterification or by stereoselective alcoholysis of 23-O acetylsilybin (2). Novozym 435 proved to be the most suitable enzyme for the preparative production of both optically pure silybins A and B by enzymatic discrimination. Gram amounts of the optically pure substances can be produced within one week, and the new method is robust and readily scalable to tens of grams. PMID- 20297829 TI - Perfectly hydrophobic surfaces with patterned nanoneedles of controllable features. AB - In this Letter, we present a simple and reproducible method for generating polystyrene (PS) nanoneedle arrays by utilizing the trapping of inorganic silica particles at the polystyrene/air interface via capillary wetting of a thermoplastic polystyrene polymer and SF(6) reactive-ion etching. A monolayer of silica microspheres was directly formed and trapped on the smooth PS film, and subsequent wet etching with HF and reactive-ion etching with SF(6) left behind hexagonal arrays of protruding tips with tip diameters around 20 nm. The patterned PS surface possessed a well-defined nanoneedle array with the pattern density as high as 2.5 x 10(8)/cm(2) and exhibited advancing and receding water contact angles of 180 degrees. The surface showed no affinity for water as confirmed by a series of contact, compression, and release tests. Finally, the perfect hydrophobicity of the fabricated surface is explained in terms of its surface morphology and chemical composition. PMID- 20297827 TI - Regioselective and stereoselective cyclizations of chloropolyols in water: rapid synthesis of hydroxytetrahydrofurans. AB - A concise, stereoselective synthesis of functionalized tetrahydrofuranols has been developed that involves heating readily available chloropolyols in water. These reactions are operationally straightforward and chemoselective for the formation of tetrahydrofurans, obviating the need for complicated protecting group strategies. The efficiency of this process is demonstrated in a short asymmetric synthesis of the natural product (+)-goniothalesdiol. PMID- 20297828 TI - Morphological changes in vesicles and release of an encapsulated compound triggered by a photoresponsive Malachite Green leuconitrile derivative. AB - Photoinduced morphological changes in phosphatidylcholine vesicles are triggered by a Malachite Green leuconitrile derivative dissolved in the lipidic membrane, and are observed at Malachite Green derivative/lipid ratios <5 mol %. This Malachite Green derivative is a photoresponsive compound that undergoes ionization to afford a positive charge on the molecule by UV irradiation. The Malachite Green derivative exhibits amphiphilicity when ionized photochemically, whereas it behaves as a lipophilic compound under dark conditions. Cryo transmission electron microscopy was used to determine vesicle morphology. The effects of the Malachite Green derivative on vesicles were studied by dynamic light scattering and fluorescence resonance energy transfer. Irradiation of vesicles containing the Malachite Green derivative induces nonspherical vesicle morphology, fusion of vesicles, and membrane solubilization, depending on conditions. Furthermore, irradiation of the Malachite Green derivative induces the release of a vesicle-encapsulated compound. PMID- 20297830 TI - Immobilization of zinc porphyrin complexes on pyridine-functionalized glass surfaces. AB - In order to immobilize sublimable and fluorescent dye molecules on transparent surfaces for the detection of far field molecular interference experiments, we investigate the potential of pyridine-functionalized glass substrates as coordination sites for the zinc complex of tetraphenylporphyrin (ZnTPP). Borosilicate glass is functionalized with 4-(6 (ethoxydimethylsilyl)hexyloxy)pyridine in order to cover the glass surface with pyridine subunits. ZnTPP molecules are deposited by sublimation through mechanical masks of various sizes in a high-vacuum chamber. The resulting micropatterns are analyzed using epifluorescence microscopy which also allows us to define a measure for the quality of molecular immobilization. We observe a reduced mobility and an increased efficiency for the trapping of ZnTPP on pyridine-functionalized surfaces. PMID- 20297831 TI - Stress fluctuations in drying polymer dispersions. AB - Drying polymer dispersions usually experience tensile stress, induced by the reduction in volume and by the rigid substrate. Due to edge-in drying, the stress is usually heterogeneous over the film. Stress peaks play a decisive role in the formation of cracks. This work relies on membrane bending, a technique that provides spatially resolved stress maps. In the experiments reported here, stress fluctuations on the order of 10% on the time scale of a few seconds were found. The stress fluctuations occur coherently over the entire drying front. Fluctuations go back to slight fluctuations in humidity of the environment (as opposed to local stress relaxations due to reorganizations of the particle network). The stress fluctuations disappear when covering the sample with a lid. They can be enhanced by blowing humid or dry air across the sample surface. Modeling builds on the assumption that all stresses go back to capillary pressure created at the menisci in between different spheres at the film-air interface. The local radius of curvature changes in response to slight variations in ambient humidity according to the Kelvin equation. The fluctuations are observed under a wide variety of drying conditions and should be included in film formation models. PMID- 20297832 TI - Physicochemical characterization and surface acid properties of mesoporous [Al] SBA-15 obtained by direct synthesis. AB - In this work, [Al]-SBA-15 samples were prepared by three different direct synthesis methods and one postsynthesis procedure, aiming to study the influence of the preparation procedures on their structural, textural, and physicochemical features. To this aim, samples were investigated by combining different experimental techniques (XRD, N(2) physisorption, (27)Al-MAS NMR, and IR spectroscopy). All preparation methods led to the formation of aluminum containing SBA-15 samples. Nevertheless, depending on the preparation procedure, samples exhibited different structural, textural, and surface characteristics, especially in terms of Bronsted and Lewis acid sites content. [Al]-SBA-15(1) was synthesized by the pH-adjusting method and presented the lowest surface area and pore volumes. Its surface displayed three families of medium and one family of high strength Bronsted acid sites. The Bronsted/Lewis ratio was 3.49. [Al]-SBA 15(2) and [Al]-SBA-15(3) were synthesized by prehydrolysis of the silica and the aluminum precursors. In [Al]-SBA-15(2), ammonium fluoride was used as silica condensation catalyst. These two materials presented similar surface area, pore diameters and volumes, and Bronsted acidity. The Bronsted/Lewis acid sites ratio were 3.07 and 2.15 for [Al]-SBA-15(2) and [Al]-SBA-15(3), respectively. The [Al] SBA-15(P) obtained by postsynthesis alumination displayed surface area similar to that of [Al]-SBA-15(3), Bronsted/Lewis acid sites ratio of 2.75, and Bronsted acidity similar to that of [Al]-SBA-15(1). The presence of extra-framework aluminum oxide was identified only on [Al]-SBA-15(3) and [Al]-SBA-15(P). PMID- 20297833 TI - Molecular scale characterization of the titania-dye-solvent interface in dye sensitized solar cells. AB - Charge separation at the dye/titania interface in dye sensitized solar cells is strongly influenced by the thickness and homogeneity of the sensitizing dye layer, as this controls the potential drop across the interface, and the probability of an excited electron being transferred from the dye to the titania. In this study we use atomic force microscopy and the depth profiling method neutral impact collision ion scattering spectroscopy (NICISS) to investigate the thickness and homogeneity of N719 dye adsorbed to titania before and after rinsing with pure acetonitrile. Both experimental methods show that the dye layers are closed but inhomogeneous. Inhomogeneity is more pronounced for unrinsed samples. PMID- 20297835 TI - Salt-induced gelation of globular protein aggregates: structure and kinetics. AB - Aggregates of the globular protein beta-lactoglobulin were formed by heating solutions of native proteins at pH 7, after which gels were formed by the addition of salt. The second step does not necessitate elevated temperatures and is therefore often called cold gelation. The structure of the gels was studied during their formation using light scattering and turbidity. Complementary confocal laser scanning microscopy measurements were done. We compared the structure with that of gels formed by heating native beta-lactoglobulin under the same conditions. Whereas in the latter case, microphase separation occurs above 0.2 M NaCl, no microphase separation was observed during cold gelation up to at least 1 M NaCl. The dependence of the kinetics and the final gel structure on the protein concentration, the temperature, the salt concentration, and the aggregate size was quantified. A few measurements on gels formed by adding CaCl(2) confirmed the higher efficiency of this bivalent cation but revealed no qualitative differences with gels formed by adding NaCl. PMID- 20297834 TI - Use of aryl chlorides as electrophiles in Pd-catalyzed alkene difunctionalization reactions. AB - The development of conditions that allow use of inexpensive aryl chlorides as electrophiles in Pd-catalyzed alkene carboamination and carboetherification reactions is described. A catalyst composed of Pd(OAc)(2) and S-Phos minimizes N arylation of the substrate and prevents formation of mixtures of regioisomeric products. A number of heterocycles, including pyrrolidines, isoxazolidines, tetrahydrofurans, and pyrazolidines, are efficiently generated with this method. PMID- 20297836 TI - N,N'-diamidoketenimines via coupling of isocyanides to an N-heterocyclic carbene. AB - Treatment of an N-heterocyclic carbene that features two amide groups N-bound to the carbene nucleus with various organic isocyanides afforded a new class of ketenimines in yields of up to 96% (isolated). DFT analyses revealed that the carbene exhibits a unique, low-lying LUMO, which may explain the atypical reactivity observed. PMID- 20297837 TI - Ga(OTf)3-promoted sequential reactions via sulfur-assisted propargyl-allenyl isomerizations and intramolecular [4 + 2] cycloaddition for the synthesis of 1,3 dihydrobenzo[c]thiophenes. AB - A Ga(OTf)(3)-promoted sequential reactions via sulfur-assisted propargyl-allenyl isomerizations and intramolecular [4 + 2] cycloaddition for the synthesis of 1,3 dihydrobenzo[c]thiophenes. As a result of the ready availability of materials and the simple and convenient operation, the type of reaction presented here has potential utility in organic synthesis. PMID- 20297838 TI - Good, bad news on European PCB exposure. PMID- 20297839 TI - Researchers find little-known PCB "pretty much everywhere". PMID- 20297840 TI - Structures of human carbonic anhydrase II/inhibitor complexes reveal a second binding site for steroidal and nonsteroidal inhibitors. AB - Carbonic anhydrase (CA) catalyzes the reversible hydration of carbon dioxide to hydrogen carbonate, and its role in maintaining pH balance has made it an attractive drug target. Steroidal sulfamate esters, inhibitors of the cancer drug target steroid sulfatase (STS), are sequestered in vivo by CA II in red blood cells, which may be the origin of their excellent drug properties. Understanding the structural basis of this is important for drug design. Structures of CA II complexed with 2-methoxyestradiol 3-O-sulfamate (3), 2-ethylestradiol 3,17-O,O bis(sulfamate) (4), and 2-methoxyestradiol 17-O-sulfamate (5) are reported to 2.10, 1.85, and 1.64 A, respectively. Inhibitor 3 interacts with the active site Zn(II) ion through the 3-O-sulfamate, while inhibitors 4 and 5 bind through their 17-O-sulfamate. Comparison of the IC(50) values for CA II inhibition gave respective values of 56, 662, 2113, 169, 770, and 86 nM for estrone 3-O-sulfamate (1), 2-methoxyestradiol 3,17-O,O-bis(sulfamate) (2), 3, 4, 5, and 5'-((4H-1,2,4 triazol-4-yl)methyl)-3-chloro-2'-cyanobiphenyl-4-yl sulfamate (6), a nonsteroidal dual aromatase-sulfatase inhibitor. Inhibitors 2, 5, and 6 showed binding to a second adjacent site that is capable of binding both steroidal and nonsteroidal ligands. Examination of both IC(50) values and crystal structures suggests that 2 substituents on the steroid nucleus hinder binding via a 3-O-sulfamate, leading to coordination through a 17-O-sulfamate if present. These results underline the influence of small structural changes on affinity and mode of binding, the degree of flexibility in the design of sulfamate-based inhibitors, and suggest a strategy for inhibitors which interact with both the active site and the second adjacent binding site simultaneously that could be both potent and selective. PMID- 20297841 TI - Tyrosinase inhibitory constituents from the roots of Morus nigra: a structure activity relationship study. AB - The phytochemical profiles of Morus nigra roots and twigs were compared by HPLC with those of the old and young twigs of Morus alba which are known to contain oxyresveratrol and mulberroside A as major components. It was found that M. nigra root extract contains some unknown natural products with potential tyrosinase inhibitory activity. The extract (95% ethanol) of the roots of M. nigra was further investigated in this study. One new compound, 5'-geranyl-5,7,2',4' tetrahydroxyflavone, and twenty-eight known phenolic compounds were isolated. Their structures were identified by mass spectrometry and NMR spectroscopy. Nine compounds, 5'-geranyl-5,7,2',4'-tetrahydroxyflavone, steppogenin-7-O-beta-D glucoside, 2,4,2',4'-tetrahydroxychalcone, moracin N, kuwanon H, mulberrofuran G, morachalcone A, oxyresveratrol-3'-O-beta-D-glucopyranoside and oxyresveratrol-2-O beta-D-glucopyranoside, showed better tyrosinase inhibitory activities than kojic acid. It was noteworthy that the IC(50) values of 2,4,2',4'-tetrahydroxychalcone and morachalcone A were 757-fold and 328-fold lower than that of kojic acid, respectively, suggesting a great potential for their development as effective natural tyrosinase inhibitors. PMID- 20297842 TI - Density functional modeling of the local structure of kaolinite subjected to thermal dehydroxylation. AB - Understanding the atomic-level changes that occur as kaolinite is converted (thermally dehydroxylated) to metakaolin is critical to the optimization of this large-scale industrial process. Metakaolin is X-ray amorphous; therefore, conventional crystallographic techniques do not reveal the changes in local structure during its formation. Local structure-based experimental techniques are useful in understanding the atomic structure but do not provide the thermodynamic information which is necessary to ensure plausibility of refined structures. Here, kaolinite dehydroxylation is modeled using density functional theory, and a stepwise methodology, where several water molecules are removed from the structure, geometry optimization is carried out, and then the process is repeated. Hence, the structure remains in an energetically and thermodynamically feasible state while transitioning from kaolinite to metakaolin. The structures generated during the dehydroxylation process are validated by comparison with X ray and neutron pair distribution function data. Thus, this study illustrates one possible route by which dehydroxylation of kaolinite can take place, revealing a chemically, energetically, and experimentally plausible structure of metakaolin. This methodology of density functional modeling of the stepwise changes in a material is not limited in application to kaolinite or other aluminosilicates and provides an accurate representation of the local structural changes occurring in materials used in industrially important processes. PMID- 20297843 TI - Density functional theory calculations of the molecular force field of L-ascorbic acid, vitamin C. AB - We have studied L-ascorbic acid and characterized it by infrared spectroscopy in solid and aqueous solution phases. The density functional theory (DFT) method together with Pople's basis set show that three stable molecules for the compound have been theoretically determined in the gas phase, and that an average of only two more stable conformations are present in the solid phase, as it was experimentally observed. The harmonic vibrational wavenumbers for the optimized geometries of both structures were calculated at B3LYP/6-31G*and B3LYP/6-311++G** levels at the proximity of the isolated molecule. For a complete assignment of the vibrational spectra in the compound solid and aqueous solution phases, DFT calculations were combined with Pulay's scaled quantum mechanics force field methodology in order to fit the theoretical wavenumber values to the experimental ones. In this way, a complete assignment of all the observed bands in the infrared spectrum for l-ascorbic acid was performed. The natural bond orbital study reveals the characteristics of the electronic delocalization of the three structures while the corresponding topological properties of electronic charge density are analyzed by employing Bader's atoms-in-molecules theory. PMID- 20297844 TI - Drug- and lead-likeness, target class, and molecular diversity analysis of 7.9 million commercially available organic compounds provided by 29 suppliers. AB - A database of 7.9 million compounds commercially available from 29 suppliers in 2008-2009 was assembled and analyzed. 5.2 million structures of this database were identified to be unique and were subjected to an assessment of physical and biological properties and estimation of molecular diversity. The rules of Lipinski and Veber were applied to the molecular weight, the calculated water/n octanol partition coefficients (Clog P), the calculated aqueous solubility (log S), the numbers of hydrogen-bond donors and acceptors, and the calculated Caco-2 membrane permeability to identify the drug-like compounds, whereas the toxicity/reactivity filters were used to remove the structures with biologically undesired functional groups. This filtering resulted in 2.0 million (39%) structures perfectly suitable for high-throughput screening of biological activity. Modified filters applied to identify lead-like structures revealed that 16% of the unique compounds could be potential leads. Assessment of the biological activities, the analysis of diversity, and the sizes of exclusive sets of compounds are presented. PMID- 20297845 TI - Production of biovanillin by one-step biotransformation using fungus Pycnoporous cinnabarinus. AB - The current study proposes a one-step biotransformation process for vanillin production from ferulic acid using the wild fungal strain Pycnoporous cinnabarinus belonging to the family Basidiomycete. Improvement of biotransformation conditions was performed in two steps; initially a one factor at a time method was used to investigate effects of medium composition variables (i.e., carbon, nitrogen) and environmental factors such as pH on vanillin production. Subsequently, concentrations of medium components were optimized using an orthogonal matrix method. After primary screening, glucose as carbon source and corn steep liquor and ammonium chloride as organic and inorganic nitrogen source, respectively, supported maximum biotransformation of ferulic acid to vanillin. Under statistically optimum conditions vanillin production from ferulic acid by P. cinnabarinus was 126 mg/L with a molar yield of 54%. The overall molar yield of vanillin production increased by 4 times. PMID- 20297846 TI - Discovery of novel small molecule orally bioavailable C-X-C chemokine receptor 4 antagonists that are potent inhibitors of T-tropic (X4) HIV-1 replication. AB - The redesign of azamacrocyclic CXCR4 chemokine receptor antagonists resulted in the discovery of novel, small molecule, orally bioavailable compounds that retained T-tropic (CXCR4 using, X4) anti-HIV-1 activity. A structure-activity relationship (SAR) was determined on the basis of the inhibition of replication of X4 HIV-1 NL4.3 in MT-4 cells. As a result of lead optimization, we identified (S)-N'-((1H-benzo[d]imidazol-2-yl)methyl)-N'-(5,6,7,8-tetrahydroquinolin-8 yl)butane-1,4-diamine (AMD070) 2 as a potent and selective antagonist of CXCR4 with an IC(50) value of 13 nM in a CXCR4 125I-SDF inhibition binding assay. Compound 2 inhibited the replication of T-tropic HIV-1 (NL4.3 strain) in MT-4 cells and PBMCs with an IC(50) of 2 and 26 nM, respectively, while remaining noncytotoxic to cells at concentrations exceeding 23 microM. The pharmacokinetics of 2 was evaluated in rat and dog, and good oral bioavailability was observed in both species. This compound represents the first small molecule orally bioavailable CXCR4 antagonist that was developed for the treatment of HIV-1 infection. PMID- 20297847 TI - Comparison of solid-state dipolar couplings and solution relaxation data provides insight into protein backbone dynamics. AB - Analyses of solution (15)N relaxation data and solid-state (1)H(N)-(15)N dipolar couplings from a small globular protein, alpha-spectrin SH3 domain, produce a surprisingly similar pattern of order parameters. This result suggests that there is little or no ns-mus dynamics throughout most of the sequence and, in particular, in the structured portion of the backbone. At the same time, evidence of ns-mus motions is found in the flexible loops and termini. These findings, corroborated by the MD simulations of alpha-spectrin SH3 in a hydrated crystalline environment and in solution, are consistent with the picture of protein dynamics that has recently emerged from the solution studies employing residual dipolar couplings. PMID- 20297848 TI - Copper-catalyzed amination of primary benzylic C-H bonds with primary and secondary sulfonamides. AB - A room-temperature, copper-catalyzed amination of primary benzylic C-H bonds with primary and secondary sulfonamides is described. The reaction is applicable to the coupling of a range of primary and secondary benzylic hydrocarbons with a diverse set of sulfonamides and is tolerant of substitution on both coupling partners. Factors which influence the selectivity of C-H functionalization between primary and secondary sites are examined. PMID- 20297849 TI - Organic linking. PMID- 20297853 TI - Defining and measuring functional recovery from depression. AB - Depression is associated with significant functional impairment and reduced quality of life. Disruptions occur both globally as well as in specific functional areas such as work, interpersonal relationships and cognitive function. From both a clinical and research perspective, much focus has been given to the resolution of symptoms associated with depression, while relatively little attention has been given to functional improvements. Definitions of remission in depression are most frequently based on achieving a cut-off score on clinical rating scales of depressive symptoms. Research in this area has sparsely included psychosocial function or health-related quality of life as a primary outcome measure in clinical trials. However, the need to fully understand the impact of depression and its treatments on functioning is great, given the existing evidence of the profound effect that depression has on function. Even mild depressive symptoms and subsyndromal depression result in functional impairment and reduced quality of life, and untreated residual depressive symptomatology can result in an increased likelihood for relapse of the fully symptomatic disorder (i.e. major depressive disorder). Therefore, clinicians and researchers alike need to broaden the focus of treatment to encompass not only the specific symptoms of depression, but the functional consequences as well. Many tools have been developed to assess function and quality of life, both globally as well as within specific domains. In addition, the effect of residual symptoms associated with functional impairment (i.e. insomnia, fatigue, pain [somatic] symptoms and cognition) in depression, even independently of depressive symptoms, warrants evaluation and monitoring. Recommendations for evaluating functional outcomes include: (i) adequately assessing functional impairment; (ii) identifying and/or developing treatment plans that will target symptoms associated with functional impairments; and (iii) monitoring functional impairments and associated symptoms throughout the course of treatment. The development of treatments that specifically target improvements in functional impairments is needed, and may require the use of novel treatment strategies. PMID- 20297854 TI - Childhood medulloblastoma: current status of biology and treatment. AB - Medulloblastoma, a primitive neuro-ectodermal tumour that arises in the posterior fossa, is the most common malignant brain tumour occurring in childhood. Over the past half century, the long-term survival for children with medulloblastoma has improved remarkably from a certain fatal diagnosis to a cancer that is often curable. Although overall survival for children with non-disseminated and non anaplastic medulloblastoma can approach 80%, the current multidisciplinary therapeutic approach is not without long-term sequelae. Chemotherapy has improved the long-term survival and allowed for reductions in the amount of radiation given, thereby reducing some of the long-term toxicities. In this review, we describe the current understanding of the basic biology of medulloblastoma and report on the current active chemotherapeutic agents utilized in medulloblastoma therapy. Ultimately, our understanding of the basic biology of medulloblastoma may lead to further advances in therapy by providing targets that are more specific and potentially less toxic. PMID- 20297856 TI - For what diagnoses are psychotropic medications being prescribed?: a nationally representative survey of physicians. AB - BACKGROUND: Psychoactive medications, such as antidepressants, are one of the most widely prescribed categories of drugs in the US; yet few studies have comprehensively examined the conditions for which psychoactive medications are prescribed. To our knowledge, no prior study has examined the extent to which psychoactive medications are prescribed for non-psychiatric somatic illnesses or the main types of psychiatric disorders for which psychoactive medications are being used. OBJECTIVE: To examine the diagnoses for which psychiatric medications are being prescribed in the US by analysing data from a nationally representative survey of physicians. METHODS: The data were obtained from the 2005 National Disease and Therapeutic Index (NDTI), a continuing survey of a US office-based panel of physicians. The 2005 physician panel consisted of approximately 4000 physicians reporting quarterly, which was projected to a universe of 500,722 physicians. The study focused on the diagnoses that were given as the primary reason for prescribing the following types of psychotropic medications: antidepressants, antipsychotics and anti-anxiety medications. RESULTS: Of the total number of antidepressant drug mentions, 92.7% were prescribed for psychiatric conditions. The most common (65.3%) were mood disorders (e.g. depression), followed by anxiety disorders (16.4%), which together comprised 81.7% of all antidepressant drug mentions. Of the total number of anti-anxiety drug mentions, 67.7% were prescribed for psychiatric conditions. The most common diagnosis was anxiety disorders (comprising 39.6% of all drug mentions), followed by mood disorders (comprising 18.9% of all drug mentions). Almost one-third of anxiety medication drug mentions were for non-psychiatric conditions or conditions of unspecified type. Of the total number of antipsychotic drug mentions, 98.9% were prescribed for psychiatric conditions. The most common diagnoses, comprising 39.0% of all drug mentions, were mood disorders such as depression and bipolar disorder. The second most common psychiatric diagnosis was schizophrenia or other psychotic disorders, comprising 34.5% of drug mentions. Approximately 7.4% of drug mentions were for delirium, dementia, amnestic or other cognitive disorders. Attention-deficit/conduct/disruptive behaviour disorders were the diagnoses indicated on 5.7% of all antipsychotic drug mentions. Anxiety disorders were indicated on 5.5% of antipsychotic drug mentions. Disorders usually diagnosed in infancy/childhood/adolescence (e.g. autism) comprised 2.3% of antipsychotic drug mentions. CONCLUSIONS: This research provides a broad view of the nature of psychoactive medication prescribing, which may serve as a guide to future research, policy and education about these medications, their perceived benefits and risks, and their uses. PMID- 20297855 TI - Cholinesterase inhibitors as adjunctive therapy in patients with schizophrenia and schizoaffective disorder: a review and meta-analysis of the literature. AB - BACKGROUND: Cognitive deficits have been described in patients with schizophrenia from the first descriptions of dementia praecox to current concepts of cognitive dysmetria. Nevertheless, little is known about how to deal with them. In Alzheimer disease, cholinergic deficit is found and cholinesterase inhibitors have been used to delay the progression of memory and cognitive dysfunction. Several lines of evidence suggest that the cholinergic system may be disrupted in schizophrenia. OBJECTIVE: To evaluate cognitive and clinical effects of adjunctive cholinesterase inhibitors in patients with schizophrenia and schizoaffective disorder. METHOD: We conducted a literature search on PubMed and EMBASE (up to December 2008) for articles that investigated adjunctive cholinesterase inhibitors in patients with schizophrenia. The terms 'schizophrenia', 'acetylcholinesterase inhibitors', 'rivastigmine', 'donepezil', 'galantamine' and 'cognitive deficit' were searched with restriction for English language and without a year limit. All articles that presented original data from randomized, double-blind, placebo-controlled trials with donepezil, rivastigmine or galantamine in patients with schizophrenia or schizoaffective disorder were included in the meta-analysis. Studies were excluded for the following reasons: (i) case study/letter/correspondence/review; (ii) animal study; (iii) molecular/genetic investigation; and (iv) inclusion of patients with schizophrenia and co-morbid dementia. Few appropriate data for meta-analysis were found because of the large heterogeneity of the assessment instruments used. Nevertheless, effects of cholinesterase inhibitors in some cognitive domains (executive function, memory and language), psychopathology (using the Positive and Negative Syndrome Scale) and extrapyramidal symptoms could be analysed. RESULTS: Six open-label and 24 double-blind studies were found. In five open label studies there was an improvement in memory, attention and executive functions. Thirteen double-blind studies (four with rivastigmine, six with donepezil and three with galantamine) contributed to the meta-analysis. Significant improvement was found in this analysis for memory and the Trail Making test part A. CONCLUSIONS: The reviewed studies suggest that specific cognitive deficits (memory, and the motor speed and attention part of executive function) of patients with schizophrenia and schizoaffective disorder are responsive to rivastigmine, donepezil and galantamine as adjunctive therapy. Confirmatory studies are needed to determine the clinical utility of this treatment strategy. PMID- 20297857 TI - Pramipexole extended release: in Parkinson's disease. AB - Pramipexole extended release (ER) is a non-ergolinic dopamine receptor agonist available for use as a once-daily oral treatment for the signs and symptoms of early and advanced idiopathic Parkinson's disease. Once-daily pramipexole ER and three times-daily pramipexole immediate release (IR) have similar exposure over 24 hours. The ER formulation is associated with fewer fluctuations in plasma pramipexole concentrations over this period. Pramipexole ER improved the symptoms of Parkinson's disease in three well designed trials in adults with early or advanced disease, as measured by changes from baseline in the sum of the Unified Parkinson's Disease Rating Scale (UPDRS) parts II and III subtotal scores. In a 9 week study, the majority of patients with early Parkinson's disease who were receiving stable pramipexole IR treatment were successfully switched to pramipexole ER. Relative to placebo at week 18, pramipexole ER 0.375-4.5 mg (of the salt) once daily significantly decreased the sum of the UPDRS parts II and III subtotal scores from baseline in two trials in patients with early or advanced Parkinson's disease, and also reduced the percentage of off-time during waking hours in patients with advanced disease. The efficacy of pramipexole ER was maintained after 33 weeks of treatment in the trials in patients with early or advanced Parkinson's disease. Pramipexole ER was generally well tolerated in patients with Parkinson's disease, with the rate of adverse events being generally similar to that with pramipexole IR. PMID- 20297858 TI - OROS hydromorphone prolonged release: a review of its use in the management of chronic, moderate to severe pain. AB - OROS hydromorphone prolonged release (OROS hydromorphone) [Jurnista] is a once daily formulation of the opioid agonist hydromorphone that utilizes OROS (osmotic controlled release oral delivery system) technology to deliver the drug at a near constant rate, thereby providing consistent analgesia over a 24-hour period. It is indicated for use in patients with severe pain and contraindicated in those with acute or post-operative pain. In several, randomized, multicentre, phase III trials, oral OROS hydromorphone administered once daily for up to 52 weeks was generally effective in the treatment of patients with chronic, moderate to severe cancer or nonmalignant/noncancer pain with regard to improvements from baseline to endpoint in patient-assessed measures of pain intensity, pain relief and/or functional impairment. Pharmacoeconomic analyses suggest that OROS hydromorphone provides greater cost utility than other opioids in this patient population. In addition, OROS hydromorphone was generally well tolerated in clinical trials, with most adverse events being mild to moderate in severity and similar to those seen with other opioids. Thus, OROS hydromorphone is an effective and useful alternative to other opioids for the treatment of patients with severe pain. PMID- 20297859 TI - Is there still a role for desmopressin in children with primary monosymptomatic nocturnal enuresis?: a focus on safety issues. AB - It has recently became apparent that severe primary monosymptomatic nocturnal enuresis (MNE) has a worse prognosis than generally believed, and may have major consequences on the well-being of the child, thus making treatment mandatory. Desmopressin is one of the most widely prescribed medications for MNE, and in this current opinion article we discuss the safety of desmopressin in children with this condition. Following a US FDA request in December 2007 that the prescribing information for desmopressin nasal spray be updated, desmopressin spray is no longer indicated for the treatment of MNE or for use in patients at risk for hyponatraemia. Multiple reports of hyponatraemia in patients with nocturia (mainly the elderly) led to an increased awareness of the risks associated with desmopressin. While the pathogenesis of hyponatraemia in those over 65 years of age relates more to changing renal water and solute handling, we believe that in the young, overdosing and insufficient fluid restriction are usually the major causes. Hyponatraemia is most frequently reported when desmopressin is administered by nasal spray compared with the tablet formulation. This may simply reflect the fact that for more than 10 years the spray was the only available mode of administration in many countries. However, it may also reflect the higher biodisponibility and/or intraindividual variability of pharmacokinetics of the spray compared with the tablet. There are few serious adverse events reported for the melt formulation (oral lyophilisate), but as it has only recently become available on the market, it would be premature to conclude that it has a better safety profile. We believe that desmopressin in all formulations has a good safety profile in children with MNE, provided that treatment is properly prescribed and monitored; improving the training of doctors and patients in the dose-response kinetics of the drug, teaching appropriate restriction of fluid intake and by encouraging the use of desmopressin within a narrow dose range (10-20 microg spray, 120-240 microg melt and 200-400 microg tablet) when used in primary-care settings. Titrating higher doses in therapy resistant patients should probably be carried out in a specialized enuresis centre, and only after documenting adequate morning urinary diluting capacity. In summary, the risk of hyponatraemia is exacerbated by misuse of the drug rather than an inherent danger associated with the drug, which in our opinion should be addressed with better education rather than withdrawal of a medication that has the potential to benefit children with nocturnal enuresis. PMID- 20297860 TI - Cerebrovascular accidents in elderly people treated with antipsychotic drugs: a systematic review. AB - After 2002, an association between stroke and antipsychotic use was reported in clinical trials and large database studies. This review considers previous quantitative reviews, newly published clinical trials, and recent observational cohort and case-control studies, and focuses on the clinical significance of the risk for stroke, the difference between typical and atypical antipsychotics, the possible at-risk patient profile and the timing of stroke after exposure. A search of MEDLINE covering the period from 1966 to June 2009 was carried out using selected keywords. Inclusion criteria were (i) quantitative reviews on stroke and antipsychotics; (ii) double-blind, placebo-controlled clinical trials involving patients with dementia treated with antipsychotics; and (iii) observational database cohort studies and observational case-control studies investigating the association between stroke and antipsychotics. Clinical trials were excluded if they were single-blind or if patients were affected by dementia and/or other neurological illnesses. Four reviews with aggregate data, 2 meta analyses, 13 randomized, double-blind, controlled trials, 7 observational cohort studies and 4 observational case-control studies were selected and analysed. The incidence of cerebrovascular accidents (CVAs) was found to be very low in aggregate reviews and meta-analyses (2-4%). When the number collected was sufficiently high, or different drug treatments were grouped together, the higher rate in subjects exposed to antipsychotics was statistically significant. Inspection of other randomized controlled clinical trials, not included in aggregate reviews and meta-analyses, reported similar rates of CVAs. The majority of observational cohort studies compared typical and atypical antipsychotics and no significant class differences were found. A comparison with non-users was carried out in some cohort studies. In case-control studies, the probability of CVAs in users compared with non-users was in the range of 1.3- to 2-fold greater. Preliminary data also indicate that the highest risk of stroke is related to the first weeks of treatment, and a risk profile for stroke is emerging, such as older age, cognitive impairment and vascular illness. Different pathophysiological pathways may be involved, ranging from the facilitation of thrombosis, pre-existing cardiovascular factors, sedation and a common diathesis for stroke of dementia, schizophrenia and affective illness. Before prescribing an antipsychotic, clinicians should weigh all the risk factors for a given patient and consider not only the indications as provided by the regulatory agencies, but also the overall effectiveness of typical and atypical antipsychotics. PMID- 20297861 TI - Psychiatric adverse events in randomized, double-blind, placebo-controlled clinical trials of varenicline: a pooled analysis. AB - BACKGROUND: Varenicline (Chantix), Champix) has shown efficacy and tolerability as an aid to smoking cessation. In postmarketing surveillance, neuropsychiatric symptoms have appeared; however, their incidence and causal relationship to varenicline is not known. OBJECTIVE: We assessed the incidence and relative risk (RR) of psychiatric disorders in ten randomized, double-blind, placebo-controlled trials of varenicline for smoking cessation. METHODS: All smoking cessation phase II, III and IV randomized controlled clinical trials of varenicline versus placebo completed as of 31 December 2008, on file with the manufacturer (Pfizer, Inc.), were included. All studies have been published. All 3091 participants who received at least one dose of varenicline and all 2005 participants who received placebo were included in this analysis. These were men and women smoking > or =10 cigarettes/day, aged 18-75 years and without current psychiatric disease who received varenicline or placebo for 6 (one study), 12 (eight studies) or 52 (one study) weeks. Adverse events were recorded at each study visit and classified according to standard Medical Dictionary for Regulatory Activities (MedDRA) terms (version 11.0). RESULTS: The incidence of psychiatric disorders other than solely sleep disorders and disturbances was 10.7% in subjects treated with varenicline and 9.7% in subjects treated with placebo, with an RR of 1.02 (95% CI 0.86, 1.22). The RRs (95% CI) versus placebo of psychiatric adverse events with an incidence > or =1% in the varenicline group were 0.86 (0.67, 1.12) for anxiety disorders and symptoms, 0.76 (0.42, 1.39) for changes in physical activity, 1.42 (0.96, 2.08) for depressed mood disorders and disturbances, 1.21 (0.79, 1.83) for mood disorders and disturbances not elsewhere classified and 1.70 (1.50, 1.92) for sleep disorders and disturbances. There were no cases of suicidal ideation or behaviour in varenicline-treated subjects in the ten placebo-controlled studies analysed. However, among three trials that were excluded from the analysis because of their open-label design, two cases of suicidal ideation and one completed suicide were reported in patients who had been treated with varenicline. With the exception of sleep disorders and disturbances, there was no evidence of dose-responsivity. CONCLUSIONS: There was no significant increase in overall psychiatric disorders, other than sleep disorders and disturbances, in varenicline-treated subjects in this sample of smokers without current psychiatric disorders. Ongoing studies are testing the use of varenicline in psychiatric patients. PMID- 20297862 TI - Antimicrobials and the risk of torsades de pointes: the contribution from data mining of the US FDA Adverse Event Reporting System. AB - BACKGROUND: Drug-induced torsades de pointes (TdP) is a complex regulatory and clinical problem due to the rarity of this sometimes fatal adverse event. In this context, the US FDA Adverse Event Reporting System (AERS) is an important source of information, which can be applied to the analysis of TdP liability of marketed drugs. OBJECTIVE: To critically evaluate the risk of antimicrobial-induced TdP by detecting alert signals in the AERS, on the basis of both quantitative and qualitative analyses. METHODS: Reports of TdP from January 2004 through December 2008 were retrieved from the public version of the AERS. The absolute number of cases and reporting odds ratio as a measure of disproportionality were evaluated for each antimicrobial drug (quantitative approach). A list of drugs with suspected TdP liability (provided by the Arizona Centre of Education and Research on Therapeutics [CERT]) was used as a reference to define signals. In a further analysis, to refine signal detection, we identified TdP cases without co medications listed by Arizona CERT (qualitative approach). RESULTS: Over the 5 year period, 374 reports of TdP were retrieved: 28 antibacterials, 8 antifungals, 1 antileprosy and 26 antivirals were involved. Antimicrobials more frequently reported were levofloxacin (55) and moxifloxacin (37) among the antibacterials, fluconazole (47) and voriconazole (17) among the antifungals, and lamivudine (8) and nelfinavir (6) among the antivirals. A significant disproportionality was observed for 17 compounds, including several macrolides, fluoroquinolones, linezolid, triazole antifungals, caspofungin, indinavir and nelfinavir. With the qualitative approach, we identified the following additional drugs or fixed dose combinations, characterized by at least two TdP cases without co-medications listed by Arizona CERT: ceftriaxone, piperacillin/tazobactam, cotrimoxazole, metronidazole, ribavirin, lamivudine and lopinavir/ritonavir. DISCUSSION: Disproportionality for macrolides, fluoroquinolones and most of the azole antifungals should be viewed as 'expected' according to Arizona CERT list. By contrast, signals were generated by linezolid, caspofungin, posaconazole, indinavir and nelfinavir. Drugs detected only by the qualitative approach should be further investigated by increasing the sensitivity of the method, e.g. by searching also for the TdP surrogate marker, prolongation of the QT interval. CONCLUSIONS: The freely available version of the FDA AERS database represents an important source to detect signals of TdP. In particular, our analysis generated five signals among antimicrobials for which further investigations and active surveillance are warranted. These signals should be considered in evaluating the benefit-risk profile of these drugs. PMID- 20297863 TI - Isotretinoin use and compliance with the Dutch Pregnancy Prevention Programme: a retrospective cohort study in females of reproductive age using pharmacy dispensing data. AB - BACKGROUND: Isotretinoin is very effective in the treatment of severe acne. However, because of the teratogenic properties of this agent an isotretinoin Pregnancy Prevention Programme (PPP) was implemented in the Netherlands to guarantee that treatment is contraindicated in women of reproductive age unless at least one effective method of contraception is used. Furthermore, the PPP stipulates that isotretinoin treatment should be managed by physicians or specialists experienced in treatment with this drug and that only monthly prescriptions are issued. OBJECTIVE: To assess compliance with the Dutch isotretinoin PPP in women of reproductive age during the study period of 1 January 2005 to 31 December 2008. METHODS: Detailed information on dispensed medication and co-medication was available from the Dutch Foundation of Pharmaceutical Statistics. Four types of outcome were studied: concomitant dispensing of hormonal contraceptive with isotretinoin; the proportion of specialist prescribing of isotretinoin; prescribing of conventional acne therapy prior to isotretinoin initiation; and isotretinoin dispensing exceeding the maximum amount. The use of contraceptives in women aged between 15 and 45 years was defined as concomitant if the period of systemic contraceptive use overlapped the period of isotretinoin dispensing for at least 10 days, or if any dispensing of an intrauterine or intravaginal contraceptive was recorded since the year 2000. Dispensings were separated into those prescribed by either specialists or general practitioners (GPs). The use of antibacterials, antiandrogens or topical agents against acne was checked 4 months prior to an isotretinoin dispensing, and a possible excess of the maximum amount of isotretinoin was defined as prescriptions of more than 100 defined daily doses. RESULTS: During the study period, data were available for 442 Dutch pharmacies encompassing 4881 women of reproductive age using isotretinoin at least once during study period. Among women of reproductive age, the use of isotretinoin increased during the study period. The proportion of isotretinoin initiation with concomitant oral hormonal or intrauterine contraceptives was low (59.3% [95% CI 57.6, 61.0]). Initiation of isotretinoin by a specialist increased the chance for concomitant contraception by 26% (95% CI 6.0, 49.0); in 78.2% (95% CI 76.8, 79.6) of women, isotretinoin was initiated by a specialist. Conventional acne therapy up to 16 months prior to isotretinoin initiation was found in 70% of the women (70.3% [95% CI 66.0, 74.6]). In 1.4% (95% CI 1.0, 1.8) of cases of treatment initiation, the amount of isotretinoin dispensed on one prescription seemed too high. CONCLUSION: Attention should be paid to improving the implementation of the isotretinoin PPP. Despite clear guidelines and warnings in the product information, our study strongly suggests that concomitant use of isotretinoin and contraceptives is too low. Even though we will have missed non-pharmacological forms of contraception, these results raise doubts about the safe use of isotretinoin in women of reproductive age in the Netherlands. Furthermore, isotretinoin does not seem to be used in cases of severe acne only. Reserving isotretinoin prescribing to specialists may improve adherence to the PPP. PMID- 20297864 TI - Adverse drug reactions in the paediatric population in Denmark: a retrospective analysis of reports made to the Danish Medicines Agency from 1998 to 2007. AB - BACKGROUND: The potential risk of adverse drug reactions (ADRs) in the paediatric population has become a public health concern and regulatory agencies in Europe and the US have acknowledged that there is a need for more research in this area. Spontaneous reporting systems can provide important new information about ADRs. OBJECTIVE: To characterize ADRs in children reported in Denmark over a period of one decade. METHODS: We analysed ADRs reported to the Danish Medicines Agency from 1998 to 2007 for individuals aged from birth to 17 years. Data were analysed with respect to time, age and sex, category of ADR (System Organ Class [SOC]), seriousness, suspected medicines (level 2 of the Anatomical Therapeutic Chemical [ATC] Classification System) and type of reporter. RESULTS: 2437 ADR reports corresponding to 4500 ADRs were analysed. On average, 234 ADR reports were submitted annually, corresponding to approximately two ADRs per report. From 2003 to 2005, an increasing number of ADRs submitted per report were observed, but after 2005 the reporting rate decreased. One-half of ADRs were reported for infants from birth to 2 years of age. Similar total numbers of ADRs were reported for boys and girls. The majority of ADRs reported were from the following SOCs: general disorders and administration site conditions (31%), skin and subcutaneous tissue disorders (18%) and nervous system disorders (15%). Reports encompassed medicines from ATC group J: vaccines and anti-infectives for systemic use (65%); and ATC group N: nervous system (17%). On average, 42% of ADRs were classified as serious. ATC group N had the highest proportion of ADRs that were classified as serious. Although physicians reported approximately 90% of the ADRs, a relatively large proportion of serious ADRs were reported by other sources. CONCLUSION: In Denmark, the ADR reporting rate in the paediatric population has declined since 2005. The majority of ADRs reported in young children were reported for vaccines and anti-infectives, but also a high number of serious ADRs were reported for medicines from ATC group N. The Danish Medicines Agency should monitor prescribing patterns more tightly to identify potential risks in the paediatric population in relation to the evolving pattern of medicine use among children. PMID- 20297865 TI - Oral olanzapine disposition in adolescents with schizophrenia or bipolar I disorder: a population pharmacokinetic model. AB - BACKGROUND: Olanzapine is an atypical antipsychotic approved for the treatment of adults and adolescents (aged 13 -17 years) with schizophrenia or bipolar I disorder (manic or mixed episodes). OBJECTIVES: To characterize the pharmacokinetics of olanzapine in adolescents, to estimate the sources of variability, and to identify significant co-variates. In addition, olanzapine pharmacokinetic parameters in adolescents were compared with those in adults to guide appropriate dosing recommendations for adolescent patients. METHODS: A population pharmacokinetic modeling study was performed. The majority of pharmacokinetic data for the model came from a multicenter, open-label study in which 4.5 weeks of oral olanzapine 2.5-20 mg once daily was administered to a total of 105 patients aged 13-17 years (41.1-148 kg) who had a diagnosis of schizophrenia or bipolar I disorder. Four blood samples at steady state were obtained from each patient. Olanzapine concentrations in plasma were determined using a validated high-performance liquid chromatography method with electrochemical detection. Similar data from 11 adolescents from three previous studies were also included. A pharmacokinetic model was developed and the potential effects of patient characteristics (sex, bodyweight, age, ethnic origin) were investigated using a nonlinear mixed effects modeling program. The distributions of pharmacokinetic parameters for olanzapine in adolescents were compared with those previously reported in adults (n = 912, diagnosis of schizophrenia, olanzapine 5-20 mg/day) using the Kolmogorov-Smirnov 2-sample test. A visual predictive check was performed using Monte Carlo simulations on an external validation dataset. RESULTS: The pharmacokinetics of oral olanzapine in adolescent patients were described by a one-compartment pharmacokinetic model. The typical model estimates were 13.6 L/h (70 kg female patient) for oral clearance (CL/F) and 899 L for oral volume of distribution (V/F). Interpatient variability (40.5% for CL/F, 65.4% for V/F) and residual error (27%) were moderate. Bodyweight and sex had a significant influence on CL/F, which was lower in patients with lower weights and approximately 30% higher in males than females. Olanzapine exposure was typically 27% higher in adolescents versus adults. Approximately 77% of adolescents and adults had comparable CL/F values and 69% had comparable V/F values. CONCLUSIONS: The pharmacokinetics of oral olanzapine in adolescent patients are similar to those in adults, and are linear in the dosage range of 2.5-20 mg/day. Given the small magnitude of co-variate effects and the interpatient variability, dose adjustments based on bodyweight or sex are not necessary in adolescents. PMID- 20297866 TI - Health economic burden of patients with restless legs syndrome in a German ambulatory setting. AB - The primary characteristics of restless legs syndrome (RLS), including severe sleep disorders, restlessness in the evening and discomfort while at rest, have substantial impact on normal daily activities. Because of the high prevalence of RLS in the general population, it is necessary to evaluate the economic impact of RLS. To determine the health economic burden of patients with RLS in Germany. A total of 519 RLS patients (mean age: 65.2 +/- 11.1 years) in different stages of disease were recruited in five health centres (university hospitals, district hospitals and office-based neurologists) by applying the diagnostic criteria of the International Restless Legs Syndrome Study Group. A questionnaire was administered that assessed healthcare resource consumption as well as socioeconomic, demographic, clinical and health status. In addition, the International RLS severity scale (IRLS), Epworth Sleepiness Scale (ESS), EQ-5D and Beck Depression Inventory (BDI) were addressed in the assessment. Direct and indirect costs (euro, year 2006 values) were derived from various German economic resources and calculated from the perspective of the healthcare and transfer payment providers. We calculated average total costs over the 3-month observation period. It was determined that average total costs were euro2090 for this period. The average direct medical and non-medical costs from the perspective of the health insurance provider were determined to be euro780, with euro300 attributed to drug costs and euro354 to hospitalization costs. Average total indirect costs amounted to euro1308 and were calculated based on productivity loss, using the human capital approach. As cost-driving factors we identified disease severity according to the IRLS (p < 0.01) and ESS (p < 0.04). Health-related quality of life was determined to be substantially affected by RLS; the mean EQ-5D visual analogue scale (VAS) was 55.6, considerably lower than that of the age-matched general population. RLS places a notable financial burden on society as well as on patients and their families. More detailed studies are needed to evaluate the health economic impact of this disorder. PMID- 20297867 TI - B cell-targeted therapies for systemic lupus erythematosus: an update on clinical trial data. AB - In the past year there has been remarkable activity and some important success in the development of B cell-targeted therapies for the treatment of systemic lupus erythematosus (SLE). The most promising studies were BLISS-52 and BLISS-76, large phase III studies that demonstrated measurable efficacy for belimumab, a monoclonal antibody against B cell-activating factor (BAFF). The moderate-sized phase II/III trials EXPLORER and LUNAR that tested rituximab, an anti-CD20 monoclonal antibody, for treatment of non-renal and renal lupus, disappointed many investigators with anecdotal success in refractory patients. These rituximab trials were intended to detect a large clinical effect in patients with very active disease and this was not found. Nevertheless, arguments can be made for additional studies in targeted populations or with a change in design to detect smaller or longer-term effects. Epratuzumab, a monoclonal antibody against the B cell surface antigen CD22, and atacicept, a chimeric molecule formed by a receptor for BAFF and a proliferation-inducing ligand (APRIL) with immunoglobulin (Ig)-G, have both been promising in initial small trials and now larger clinical trials are underway. Thus, recent clinical trial data show that B cell-targeting therapies are beginning to fulfil their promise as treatments for SLE and there are good reasons to hope for further progress in the near future. PMID- 20297869 TI - Evaluation of a rural chronic disease self-management program. AB - INTRODUCTION: Internationally, the prevalence of long-term health conditions is at epidemic proportions. Australia is no exception. The Australian Government's 'Better Health Initiative' has 5 key strategies to build better health care, one of which is the adoption of self-management and self-management support. Self management allows people to manage their condition and the consequences it brings to their lives in partnership with their health providers. The purpose of this article was to report both the process and patient outcomes following the introduction of the Stanford Chronic Disease Self-Management Program (CDSMP) into an existing service in an Australian rural setting. METHODS: Implementation processes were evaluated using semi-structured interviews conducted with managers, lay and health professional course leaders and participants about positive and negative aspects of providing the CDSMP. Participant outcomes were evaluated using a modified pre-test, post-test design to evaluate changes in activity participation and self-management knowledge and skills. RESULTS: Both negative and positive aspects of providing the program were represented by two key themes: (1) program content and quality; and (2) logistics of delivery. Throughout the interviews, managers and leaders, and course participants offered recommendations that were thematically grouped into 3 categories: (1) enhancing quality; (2) improving the logistics; and (3) providing resources. Comparison of activity levels with a community sample indicated that participants had significantly decreased participation levels. Scores on the Health Education Impact Questionnaire v2 (heiQ - RETRO) demonstrated statistically better scores at post-test on the domains of 'self monitoring', 'insight' and 'health service navigation' with a trend towards significance on 3 other domains. CONCLUSIONS: Future implementation of CDSMPs in rural areas will be encouraged by these patient outcomes, and informed by the qualitative findings from managers, leaders and course participants. PMID- 20297871 TI - Parkinson's disease: health-related quality of life, economic cost, and implications of early treatment. AB - Parkinson's disease (PD) is the second most common neurodegenerative disorder, marked by progressive increases in movement-related disability, impaired balance, and nonmotor symptoms. Its prevalence in the United States is expected to double within the next 20 years as the percentage of the elderly in the population grows. Patients with PD have twice the direct medical costs of those without PD, the majority of which occur later in the disease as disability and therapy related complications increase. Greater awareness of a prodromal/premotor stage of the disease, efforts toward early and accurate diagnosis, and the continuous refinement of treatment paradigms provide an opportunity for discussion on the use of potential disease-modifying agents to slow or halt the progression of motor and nonmotor disability. Such compounds could not only significantly improve patient and caregiver quality of life, but substantially reduce direct and indirect costs. To date, numerous compounds have been evaluated in clinical trials, including coenzyme Q10, creatine, levodopa, pramipexole, rasagiline, ropinirole, and selegiline. None has demonstrated irrefutable and enduring disease-modifying qualities, although the best available clinical evidence appears most promising for rasagiline. PMID- 20297868 TI - Therapeutic interventions to enhance apolipoprotein A-I-mediated cardioprotection. AB - The principal function of high-density lipoprotein (HDL) is to facilitate the reverse cholesterol transport (RCT) and inhibition of atheroma formation. Epidemiological studies and interventional trials have suggested that HDL has cardioprotective properties. However, increasing HDL concentration may not necessarily increase RCT, especially if the increase in HDL levels is the result of inhibiting HDL cholesterol (HDL-C) flux. The results of recent phase III clinical trials utilizing a cholesterol ester transfer protein (CETP) inhibitor to increase HDL-C levels in hypoalphalipoproteinaemia have shown that this approach of elevating HDL-C levels is insufficient to combat atherosclerosis and reduce the risk of cardiovascular disease. Although there are several interventions that increase HDL-C by preventing its turnover in the circulation, a more desirable approach is to enhance de novo production of HDL in the liver and/or small intestine. To this end, our acquired knowledge of the apolipoprotein I (apo A-I) gene promoter as well as the signalling pathways that modulate its expression, has fuelled the development of novel therapeutic strategies to increase HDL-C flux. Promising pharmacological agents that selectively regulate transcription of the apo A-I gene, therapeutic strategies to de-repress apo A-I gene expression, and infusion of recombinant apo A-I or apo A-I mimetics are under development and may be clinically beneficial in the near future. PMID- 20297870 TI - Early pharmacologic treatment in Parkinson's disease. AB - Early treatment of Parkinson's disease (PD) affords an opportunity to forestall clinical progression. Levodopa is the most effective treatment for PD motor signs and symptoms, but its use is associated with the development of motor fluctuations and dyskinesias. Because of this, levodopa use is commonly withheld until the patient experiences functional disability. Other medications are available for the treatment of early PD and can be initiated at or near the time of diagnosis. Monoamine oxidase type B (MAO-B) inhibitors provide mild symptomatic benefit, delay the need for levodopa, are very well tolerated, and may provide long-term disease-modifying effects. Dopamine agonists provide moderate symptomatic benefit, delay the need for levodopa, and cause fewer motor complications than levodopa. Compared with levodopa, however, dopamine agonists cause more somnolence and sudden-onset sleep as well as impulse control disorders. The treatment of early PD depends in part on the individual patient's anticipated risk of side effects and the degree of motor improvement required. Physicians should also consider the early use of MAO-B inhibitors in light of their very good tolerability and the recent evidence suggesting long-term disease modifying effects. PMID- 20297872 TI - Early diagnosis of Parkinson's disease: recommendations from diagnostic clinical guidelines. AB - Therapeutic options for Parkinson's disease (PD) are currently limited to symptomatic agents. Levodopa is the most efficacious treatment; however, higher doses and long-term use are associated with adverse effects such as motor fluctuations and dyskinesia. Early treatment of PD with other agents such as dopamine agonists and monoamine oxidase type B inhibitors can provide symptomatic benefit and delay initiation of levodopa therapy. Early treatment of PD is contingent upon early and accurate diagnosis of the disease, which can be challenging because there are no biomarkers or neuroimaging or other clinical tests available to confirm the diagnosis. PD diagnosis is currently based on the presence or absence of various clinical features and the experience of the treating physician. A definitive diagnosis can be made only after autopsy. Moreover, the signs and symptoms present in early PD can resemble those of a number of other movement disorders, particularly other forms of parkinsonism, such as multiple system atrophy, drug-induced parkinsonism, and vascular parkinsonism, as well as diffuse Lewy body disease and essential tremor. Nevertheless, diagnosis of PD based on clinical features and response to antiparkinsonian medication can be achieved with a fairly high level of accuracy, particularly when made by a physician specializing in movement disorders. This article reviews and summarizes published recommendations for the clinical diagnosis of PD. PMID- 20297873 TI - The clinical and economic burden of anemia. AB - Anemia is a prevalent condition that goes underrecognized and undertreated, yet still carries substantial costs for payers and is a burden on the health and quality of life of those diagnosed. Clinicians should recognize anemia of chronic diseases, such as cancer, chronic kidney disease, and human immunodeficiency virus infection, as a surrogate for more severe illness. Because of its prevalence and the health consequences associated with anemia, better detection and response is needed in vulnerable patient populations. Clinicians need to be more cognizant of the symptoms of anemia and more vigilant in its treatment to ensure better outcomes both clinically and financially. PMID- 20297874 TI - The role of erythropoiesis-stimulating agents in the treatment of anemia. AB - For those affected by anemia, receiving the proper treatment can improve quality of life. The most common treatment is erythropoiesis-stimulating agents (ESAs), which can provide significant improvements in health-related quality of life for those who have anemia and comorbidities of either cancer, human immunodeficiency virus/acquired immunodeficiency syndrome, or chronic kidney disease. But the guidelines associated with ESAs can cause confusion for those tasked with prescribing them, so it is imperative that clinicians be more cognizant of the treatment recommendations for different patient populations to make the proper treatment decisions. With the multiple safety issues involved in administering ESAs, our institution prefers to err on the side of caution until these concerns are resolved. PMID- 20297875 TI - Evolving regulatory landscape with erythropoiesis-stimulating agents and impact on managed care. AB - Erythropoiesis-stimulating agents (ESAs) are a very effective treatment for reducing the need for transfusions in patients affected by anemia and either chronic kidney disease (CKD) or cancer. However, many clinicians remain wary of its use due to safety concerns. It has been shown that higher doses are associated with cardiovascular disease, stroke, or death. These concerns have spurred the US Food and Drug Administration to order Risk Evaluation and Mitigation Strategies (REMS) for clinicians prescribing ESAs to their patients. REMS are a method to ensure safety and provide clinicians and patients with an appropriate gauge of the risks and benefits associated with the administration of ESAs. Whether this restricts its use or lowers costs remains to be determined. PMID- 20297876 TI - Early management of osteoarthritis. AB - Osteoarthritis (OA) is highly prevalent and increasing in frequency; the number of patients with OA has increased by nearly 30% over the past 10 years. The primary symptom of OA is pain. Pain and other symptoms of OA may have a profound effect on quality of life (QOL), affecting both physical function and psychological parameters. The economic costs of OA are high, and include those related to treatment, those for individuals and their families who must adapt their lives and homes to the disease, and those due to lost work productivity. These considerable humanistic and economic burdens of OA provide motivation for early identification and treatment. Early diagnosis is assisted by knowledge of risk factors. Classification criteria for OA of the hand, hip, and knee developed by the American College of Rheumatology assist in diagnosis. The European League Against Rheumatism has developed an elaborate system for diagnosis of OA of the hand. Several societies have developed therapeutic guidelines, with general overall agreement between publications. Therapy of OA is multimodal and requires a combination of pharmacologic and nonpharmacologic treatments. PMID- 20297877 TI - The role of acetaminophen in the treatment of osteoarthritis. AB - The major clinical guidelines recommend the use of acetaminophen (acetyl-para aminophenol [APAP]) for the treatment of mild-to-moderate symptoms of osteoarthritis (OA) and only recommend the use of nonsteroidal anti-inflammatory drugs (NSAIDs) after APAP failure. This recommendation is based on the efficacy of APAP in treating OA and its relatively benign side-effect profile compared with NSAIDs. NSAIDs are associated with a high risk of adverse events, particularly those of the gastrointestinal (GI) tract. A large number of studies in OA have compared APAP with a variety of selective and nonselective NSAIDs and typically found greater efficacy with NSAIDs. This advantage, however, is mainly the result of increased efficacy in patients with more severe disease, and is viewed as a relatively small analgesic advantage in some studies and meta analyses. Many of these same studies have reported little or no difference in safety between APAP and NSAIDs, but these results are typically based on short term studies. Results from meta-analyses on the safety of NSAIDs almost unanimously confirm elevated risk of GI complications. The analgesic mechanism of APAP is still not well understood. However, the notion that APAP has no anti inflammatory effect has been challenged in recent years with increasing data that suggest it may have an effect on inflammation distinct from that seen with NSAIDs. A variety of mechanistic hypotheses have been proposed. PMID- 20297878 TI - Treating to target: implementing an effective diabetes care paradigm for managed care. PMID- 20297879 TI - A survey of Canadian group psychotherapy association members' perceptions of psychotherapy research. AB - The present study reports on the findings of a Canadian survey of group therapists. The survey was conducted to solicit their perspectives of psychotherapy research. The goal of the survey was to identify topics and issues that were important to group therapists. Findings from the survey suggest that group therapists are interested in research, perhaps more than one might expect. However, respondents identified a number of factors that limit the appeal of research or impede the integration of research findings into practice. Several suggestions were offered for future research and for methods of communicating the findings of research to clinicians. The survey findings call for improved communication and collaboration between researchers and clinicians in order to achieve a more meaningful integration of science and practice in the group therapy field. PMID- 20297880 TI - Bridging the practitioner-scientist gap in group psychotherapy research. AB - Bridging the practitioner-scientist gap requires a different clinical research paradigm: participatory research that encourages community agency-academic partnerships. In this context, clinicians help define priorities, determine the type of evidence that will have an impact on their practice (affecting the methods that are used to produce the evidence), and develop strategies for translating, implementing, and disseminating their findings into evidence-based practice. Within this paradigm, different roles are assumed by the partners, and sometimes these roles are blended. This paper will consider the perspectives of people who assume these different roles (clinician, researcher, and clinician researcher) with group psychotherapy as the specific focus. Finally, the establishment of a practice-research network will be discussed as a potentially promising way to better engage group therapists in research. PMID- 20297881 TI - Patient selection for psychodynamic group psychotherapy: practical and dynamic considerations. AB - Most group therapists rely on clinical interviews to screen prospective group members' suitability for long-term, open-ended, psychodynamically oriented group therapy. Faulty selection is detrimental to everyone involved and can even lead to the demise of the group. In order to avoid, or at least significantly limit, premature terminations or problematic mismatches between a patient and the rest of the group, pre-group screening needs to examine reality factors, resistance, ambivalence, and their interplay. Therapists need to be aware of countertransferential pressures that affect the screening process. The careful exploration of six specific areas during the clinical interview process increases the likelihood of optimal patient selection and participation. A selective literature review and clinical examples are provided. PMID- 20297882 TI - Groups for children and adolescents with trauma-related symptoms: outcomes and processes. AB - The study was conducted in Israel following the 2006 Lebanon war. The purpose was to examine the impact of counseling groups employing an expressive-supportive modality on children and adolescents with war-related or divorce/loss-related trauma symptoms. The 164 children were placed into 18 small groups for 10 weekly sessions. The children were screened for traumatic stress symptoms and then randomly divided into experimental and control (wait-list) conditions. All participants completed the measures of the dependent variables (trauma symptoms, anxiety), a social support measure, and group-process measures (group relationships, group cohesion, and catharsis). Results indicated a significantly sharper reduction in trauma symptoms and anxiety in the experimental group than in the control group, regardless of type of trauma. A reduction in anxiety was predicted by gains in social support and group cohesiveness. PMID- 20297883 TI - Structure and initial validation of a short form of the therapeutic factors inventory. AB - This study examined the factor structure and validity of the Therapeutic Factors Inventory-Short Form (TFI-S), a measure originally developed to assess Yalom's eleven conceptually derived therapeutic factors. Patients in a group-oriented day treatment program (n = 174) completed the TFI-S and other measures to assess concurrent and predictive validity. Four broad therapeutic factors were identified: Instillation of Hope, Secure Emotional Expression, Awareness of Interpersonal Impact, and Social Learning. Alpha coefficients ranged from .71 to .91. Significant correlations between the TFI-S factors and Group Climate Questionnaire subscales provided preliminary evidence for the concurrent validity of the TFI S. Significant relationships were also identified between the TFI-S factors and improvement in symptoms, quality of life, and interpersonal distress at the end of treatment, suggesting that the TFI-S may have predictive validity. PMID- 20297884 TI - The mystery and the magic of the group: what happens here that happens nowhere else. PMID- 20297886 TI - Richard Billow's "modes of therapeutic engagement: part I: diplomacy and integrity and part II: sincerity and authenticity". PMID- 20297885 TI - Reflections on practitioner-researcher collaborative inquiry. AB - We offer comments regarding two articles in this issue, one titled "Bridging the Practitioner-Scientist Gap in Group Psychotherapy Research" and a complementary article providing the results of a survey, entitled "A Survey of Canadian Group Psychotherapist Association Members' Perceptions of Psychotherapy Research." We also make several recommendations for collaborative research between practitioners and scientists, such as the inclusion of clinicians on the research team, practice research networks, and improved approaches to communicating clinically relevant research findings. Also discussed are reflections and recommendations from the authors' experience as scientist-practitioners. PMID- 20297887 TI - Sex and psychodynamic psychiatry: selected topics. Editors' introduction. PMID- 20297888 TI - The co-evolution of sexual desire, narcissistic vulnerability, and adaptations for reproductive advantage. AB - According to evolutionary psychologists humans possess a variety of "sexual ornaments," physical as well as psychological traits that have evolved as adaptations for reproductive advantage. These sexual ornaments serve as sexually selected indicators of fitness that are automatically assessed, inspire attentional adhesion, and evoke sexual desire in those searching for a mate. Mate choice is therefore determined by the relative presence or absence of these sexually selected indicators of fitness in comparison to the competition. Mate value of self and others is assessed through social comparison according to these sexually selected indicators of fitness. Narcissistic equilibrium is to a significant extent regulated by one's self-perceived survival and reproductive fitness. Implications for psychoanalytic theory of concepts and research findings from the field of evolutionary psychology are discussed. PMID- 20297889 TI - Psychodynamics of hypersexuality in children and adolescents with bipolar disorder. AB - It has recently become evident that bipolar disorder exists in children and adolescents. The criteria for making the diagnosis of juvenile bipolar disorder (JBD) are in the process of being proposed for the fifth edition of the Diagnostic and Statistical Manual (DSM-V). In adults, a criterion for bipolar disorder is excessive involvement in pleasurable activities including hypersexuality. Recently, some clinicians and researchers have suggested that hypersexuality be included as a criterion for JBD as well. Although abnormal sexuality has been reported to be present in some youth thought to have JBD, the reason for this association is not yet clear. Hypersexuality may be primary and intrinsic to bipolar disorder in youth, secondary and associated with it as the result of psychosocial influences or psychodynamic factors, or due to general aggression and disruptive behavior. Not only have developmental psychosocial factors that may influence sexuality in children and adolescence not been fully investigated, but psychodynamic influences have been omitted from modern etiological constructs as well. This report discusses the importance of psychosocial and psychodynamic influences on the sexual experience and activity of bipolar children. It is proposed that a developmental, psychodynamically informed model is helpful in understanding sexuality in children and adolescents with bipolar disorder. It is also suggested that assessment of psychosocial and psychodynamic influences on the sexuality of bipolar children is necessary in order to adequately assess whether hypersexuality should be a criterion of bipolar disorder in youth. PMID- 20297890 TI - Understanding and treating infertility: psychoanalytic considerations. AB - This article describes how the intrapsychic, psychosocial, and social ramifications of infertility may be addressed when infertility patients present with distress at the psychotherapist's office. Self psychology provides a valuable framework for the therapist, given the profound and multiple narcissistic assaults on self-esteem, consolidation of identity, developmental aspirations, and other self attributes which infertility causes. The therapist's empathy becomes the primary tool of both understanding and alleviating suffering resulting from infertility. The current medical and interpersonal experiences of the infertile person must be part of the therapeutic process. A psychodynamic model of treatment is outlined which includes goals of reestablishing narcissistic equilibrium, diminishing internalized stigma, and ameliorating other adverse psychological consequences of infertility diagnosis and treatment. PMID- 20297891 TI - The menstrual cycle as a subject of psychoanalytic inquiry. AB - Since the pioneering studies of Benedek and Rubenstein (1939) psychoanalytic literature has ignored the impact of the menstrual cycle on a woman's psyche. This avoidance is based in sexism and concern over the ways in which the hormonal body has been used to support a negative view of women. It is clear that the impact of the hormonal body on the psyche is an important and relevant topic for psychoanalytic inquiry. Many women experience several different self-states during the course of their menstrual cycle. Clinicians should ask questions about menstrual experience to help patients contact, articulate, and give credence to all aspects of the self. PMID- 20297892 TI - Menopause, depression, and loss of sexual desire: a psychodynamic contribution. AB - Menopause is a phase of life during which physiological and psychological symptoms may occur. Most women traverse the menopausal transition without significant morbidity. The descriptive literature on menopause indicates that the nature of psychological and physical morbidity is a function of a variety of bio psychosocial influences. There are distinct subgroups of women who are more likely to become symptomatic during this phase. Rosemary Basson has reconceptualized the female sexual response cycle. Her model allows the clinician to better understand and treat the reciprocal, interacting influences of depression, menopausal changes, and decreases in sexual desire on sexual functioning. Psychodynamic theories about menopause have moved away from the early models which predicted a universally negative experience. It is now believed that past psychological and medical problems, trauma, and the quality of interpersonal relationships are important predictors for the development of symptoms. Psychodynamic psychotherapy, in conjunction with psychoeducation, pharmacotherapy and hormone replacement therapy (HRT) may all be helpful in the treatment of symptoms. PMID- 20297893 TI - Denial of pregnancy: a psychodynamic paradigm. AB - This article discusses denial of pregnancy. It includes clinical material from 17 women who not only denied pregnancy but committed neonaticide and were evaluated for forensic reasons. The forensic issues have been discussed elsewhere and are not considered here. The literature on denial of pregnancy taken in conjunction with the clinical profiles presented here indicates that women who deny pregnancy tend to experience dissociative psychopathology. Not all pregnant women who dissociate deny pregnancy, however. This article discusses why some women who dissociate but not all develop the dramatic symptom-denial of pregnancy. PMID- 20297894 TI - Sexual sadism: a portrait of evil. AB - Sexual sadism has been defined ambiguously in the DSM to include both preoccupation with sadistic sexual fantasies and the acting out of such fantasies (with resultant harm or death to the victims). Ideally, the term should be used only for persons in whom such fantasies are acted out in actual behavior. Almost all such persons will be men. There is an overlap between the psychiatric diagnosis of sexual sadism (as behavior) and the concept of evil as the word is used in everyday parlance. The word evil is evoked generally when one comes to learn of (or witness) violent actions of such a nature as to horrify, shock, and disgust us. Evil corresponds, that is, to an emotional reaction when confronted with acts of a particularly horrifying and repugnant type. Violent sexual crimes involving torture of the victim are particularly likely to elicit this response. A common examplar of sexual sadism is the serial killer who experiences orgasm when murdering his victim. Sadistic sexual fantasies are noted in certain adolescents. In some of these the fantasies serves rehearsal for future sadistic sexual acts, especially in adolescents with callous-unemotional personality (who often emerge in adult life as psychopaths). Whereas therapy would usually fail even if such adolescents were brought to treatment early, there are others who experience sadistic sexual fantasies, but for whom these fantasies are ego-alien and disturbing. Patients of the latter type may be amenable to dynamic psychotherapy. PMID- 20297895 TI - Is love curative? AB - This article explores the phenomenon of love in the therapeutic relationship and its role as a curative factor. Since Freud's (1915) description of transference love, a major goal of treatment is to understand its developmental antecedents. Most analysts agree that transference love is no different than ordinary love, except that it is overdetermined and requires the patient to view it as simultaneously real and illusory without reciprocity from the analyst. Nontransferential, realistic elements of the therapeutic relationship also play an important role in treatment. An important outgrowth of the therapeutic process is the development of a new object relationship between analyst and patient. This special or transformative friendship is a new object relationship characterized by genuine feelings of mutual respect, trust, caring, and even love. It facilitates the patient's capacity to form and maintain other loving relationships. Two case presentations are illustrative. PMID- 20297896 TI - Psychotherapy of bisexual men. AB - We discuss clinical aspects of male bisexuality from a psychodynamic perspective. Bisexuality appears to be an attribute of some but not all men. The factors leading some men to be bisexual, and others exclusively homosexual or heterosexual are not presently known. Although bisexuality itself is not pathological, the adaptational issues of men with major psychiatric disorders who are also bisexual may be complex. PMID- 20297897 TI - Genital group B Streptococcus carrier rate and serotype distribution in Korean pregnant women: implications for group B streptococcal disease in Korean neonates. AB - AIMS: We investigated the genital group B streptococcus (GBS) carrier rate in Korean pregnant women and the serotype distribution in face of the recent increase of late-onset GBS disease in Korea. METHODS: GBS screening was performed on 4045 healthy pregnant women at 35-37 weeks' gestation. In case of positive GBS culture, serotyping was performed by using GBS typing antisera. RESULTS: When both vaginal and anorectal culture were performed, the GBS carrier rate was 10.0% (n=121/1205), which is the highest rate ever reported in Korea. Type III was more common (36%), and type Ia (13%) and Ib (7%) were less prevalent. CONCLUSIONS: Increased maternal genital GBS carrier rate and difference in serotype distribution pattern of GBS may be related to the recent increase of late-onset GBS disease in Korea. PMID- 20297898 TI - Outcomes of extremely low birth weight infants with varying doses and intervals of antenatal steroid exposure. AB - OBJECTIVE: To compare outcomes of extremely low birth weight (ELBW) infants exposed to no antenatal steroids (ANS); incomplete ANS and complete course of ANS at varying intervals prior to delivery. METHODS: A retrospective review was performed on 169 ELBW infants with ANS exposure at varied dose-intervals. The odds of mortality, intraventricular hemorrhage (IVH) and bronchopulmonary dysplasia (BPD) were compared between Group 1, infants born without ANS exposure, Group 2, infants born after one dose of ANS, Group 3, infants born after two doses of ANS given within a week, and Group 4, infants born after two doses of ANS >7 days prior to delivery. RESULTS: Mortality and IVH were significantly lower in Groups 3 (30% and 10%) and 4 (15% and 30%), compared to Groups 1 (56% and 69%) and 2 (56% and 38%). Increasing gestational age and exposure to complete course of ANS were significantly associated with decrease in mortality, BPD/mortality and IVH. Infants who received one dose of ANS had significantly lower incidence of severe IVH compared to infants without ANS exposure. CONCLUSIONS: Beneficial impact of ANS on mortality and composite BPD/mortality is evident only after a complete course and persists even with its administration beyond a week from delivery. PMID- 20297899 TI - Occult inflammation and/or ischemia may be responsible for the false positivity of biochemical Down syndrome screening test. AB - OBJECTIVE: To determine the possible underlying cause of a false-positive first or second trimester biochemical Down syndrome screening test result by means of second trimester amniotic fluid cytokine level analysis. METHODS: A total of 74 consecutive patients undergoing amniocentesis for karyotype analysis at 16-20 weeks' gestation were included in this prospective age-matched case-control study. The study group (n=38) had abnormal first or second trimester screening test results and normal karyotype results, while controls (n=36) included those admitted for genetic amniocentesis for other reasons who had normal first or second trimester screening test and normal karyotype results. Four markers [interleukin (IL)-6, IL-8, tumor necrosis factor (TNF)-alpha, and ischemia modified albumin (IMA)] were studied in amniotic fluid. RESULTS: The mean age of the women in the study and control groups was 34.0+/-5.6 and 33.6+/-7.2 years, respectively. The women in the study and control groups had similar clinical and laboratory characteristics. The mean amniotic fluid IL-6 (414.84+/-83.96 vs. 343.02+/-110.59, p=0.002) and IL-8 (377.61+/-243.31 vs. 261.90+/-201.29, p=0.029), TNF-alpha (24.91+/-5.78 vs. 21.60+/-5.55, p=0.014), and IMA (1.19+/- 0.10 vs. 1.05+/-0.12, p<0.001) values were significantly increased in the study group when compared to controls. CONCLUSION: The higher amniotic fluid cytokine and ischemia-modified albumin levels in patients with false-positive first or second trimester biochemical Down syndrome screening test may result from subclinical fetal membrane inflammation and/or ischemia. PMID- 20297900 TI - Clinical characteristics of nosocomial infections in neonatal intensive care unit in eastern China. AB - A retrospective cohort study on nosocomial infections (NI) in the neonatal intensive care unit (NICU) was performed in the Children's Hospital of Zhejiang University, Hangzhou district, China. The most common infection site was pneumonia and bloodstream infection. Low admission age, long NICU stay, and mechanical ventilation were significant risk factors for NI. Klebsiella pneumoniae was the most common pathogen, followed by Acinetobacter baumannii, Staphylococcus epidermidi, Pseudomonas aeruginosa, Enterobacter cloacae, and Stenotrophomonas maltophilia. Antibiotic resistance of the isolated bacterium was high. In conclusion, this study described the clinical characteristics of NI in a Chinese NICU, which might contribute to implementation of more effective therapeutic and preventive strategies. PMID- 20297901 TI - Validation of a model to predict hospitalization due to RSV of infants born at 33 35 weeks' gestation. AB - BACKGROUND: A model to predict hospitalization due to respiratory syncytial virus (RSV) of infants born at 33- 35 weeks' gestation was developed using seven risk factors from the Spanish FLIP study "birth +/-10 weeks from the beginning of the RSV season", "birth weight", "breast fed or=2 years", "number of family members with atopy", "number of family members with wheezing", and "gender". The aim of this study was to validate the model using French data. METHODS: The FLIP model [predictive accuracy 71%, receiver operating characteristic (ROC) 0.791] was tested against the French data (77 hospitalized infants with RSV born at 33-35 weeks and 154 age-matched controls) using discriminatory function analysis by applying the FLIP coefficients to the French data and by generating the seven variable model from the French data. RESULTS: Applying the FLIP coefficients to the French dataset, the model correctly classified 69% of cases (ROC 0.627). The predictive power increased to 73% (ROC 0.654) when "number of siblings >or=2 years" was substituted for "number of children at school". The number needed to treat (NNT) in order to prevent 70% of hospitalizations was 18. The model derived using French data could correctly classify 62% of cases in the French data (ROC 0.658). CONCLUSIONS: The model was successfully validated and may potentially optimize immunoprophylaxis in French infants born at 33-35 week's gestation. PMID- 20297902 TI - Mammalian arylsulfatase A functions as a novel component of the extracellular matrix. AB - Inherited deficiency for arylsulfatase (Ars) leads to lysosomal storage of sulfated compounds and to serious diseases such as growth retardation, heart failure, and demyelination in the central nervous system. Ars has been regarded as a lysosomal enzyme because of its hydrolytic activity on synthetic aromatic substrates and the lysosomal localization of its enzymatic activity. We previously demonstrated that a large portion of the mammalian arylsulfatase A (ArsA) protein exists on the cell surface of vascular endothelial cells, suggesting that ArsA plays a role in the components of the extracellular matrix. Here we show that ArsA functions as a substrate on which cells adhere and form protrusions. Coating culture plates with recombinant mouse ArsA (rmArsA) stimulates adhesion of human microvascular endothelial cells to the plate followed by the formation of cell protrusions as well as lamellipodia. rmArsA affects the architecture of the cytoskeleton, with a high density of actin filaments localized to peripheral regions of the cells and the extension of bundles of microtubules into the tips of cellular protrusions. rmArsA also affects the distribution pattern of the cell adhesion-associated proteins, integrin alpha2beta1, and paxillin. rmArsA seems to modulate signaling of basic fibroblast growth factor (bFGF) stimulating cytoskeletal rearrangement. We also show that rmArsA tightly binds to sulfated polysaccharides. We suggest that mammalian ArsA plays a role as a novel component of the extracellular matrix. This viewpoint of Ars could be very useful for clarifying the mechanisms underpinning syndromes caused by the deficiency of the function of Ars genes. PMID- 20297907 TI - Journal of Visual Communication in Medicine. Editorial. PMID- 20297903 TI - Development of a decellularized lung bioreactor system for bioengineering the lung: the matrix reloaded. AB - We developed a decellularized murine lung matrix bioreactor system that could be used to evaluate the potential of stem cells to regenerate lung tissue. Lungs from 2-3-month-old C57BL/6 female mice were excised en bloc with the trachea and heart, and decellularized with sequential solutions of distilled water, detergents, NaCl, and porcine pancreatic DNase. The remaining matrix was cannulated and suspended in small airway growth medium, attached to a ventilator to simulate normal, murine breathing-induced stretch. After 7 days in an incubator, lung matrices were analyzed histologically. Scanning electron microscopy and histochemical staining demonstrated that the pulmonary matrix was intact and that the geographic placement of the proximal and distal airways, alveoli and vessels, and the basement membrane of these structures all remained intact. Decellularization was confirmed by the absence of nuclear 4',6-diamidino 2-phenylindole staining and negative polymerase chain reaction for genomic DNA. Collagen content was maintained at normal levels. Elastin, laminin, and glycosaminglycans were also present, although at lower levels compared to nondecellularized lungs. The decellularized lung matrix bioreactor was capable of supporting growth of fetal alveolar type II cells. Analysis of day 7 cryosections of fetal-cell-injected lung matrices showed pro-Sp-C, cytokeratin 18, and 4',6 diamidino-2-phenylindole-positive cells lining alveolar areas that appeared to be attached to the matrix. These data illustrate the potential of using decellularized lungs as a natural three-dimensional bioengineering matrix as well as provide a model for the study of lung regeneration from pulmonary stem cells. PMID- 20297908 TI - Augmented reality for anatomical education. AB - The use of Virtual Environments has been widely reported as a method of teaching anatomy. Generally such environments only convey the shape of the anatomy to the student. We present the Bangor Augmented Reality Education Tool for Anatomy (BARETA), a system that combines Augmented Reality (AR) technology with models produced using Rapid Prototyping (RP) technology, to provide the student with stimulation for touch as well as sight. The principal aims of this work were to provide an interface more intuitive than a mouse and keyboard, and to evaluate such a system as a viable supplement to traditional cadaver based education. PMID- 20297909 TI - The strategic value of user experience. PMID- 20297912 TI - Extracorporeal photopheresis. PMID- 20297904 TI - Microneedle-based drug delivery systems: microfabrication, drug delivery, and safety. AB - Many promising therapeutic agents are limited by their inability to reach the systemic circulation, due to the excellent barrier properties of biological membranes, such as the stratum corneum (SC) of the skin or the sclera/cornea of the eye and others. The outermost layer of the skin, the SC, is the principal barrier to topically-applied medications. The intact SC thus provides the main barrier to exogenous substances, including drugs. Only drugs with very specific physicochemical properties (molecular weight < 500 Da, adequate lipophilicity, and low melting point) can be successfully administered transdermally. Transdermal delivery of hydrophilic drugs and macromolecular agents of interest, including peptides, DNA, and small interfering RNA is problematic. Therefore, facilitation of drug penetration through the SC may involve by-pass or reversible disruption of SC molecular architecture. Microneedles (MNs), when used to puncture skin, will by-pass the SC and create transient aqueous transport pathways of micron dimensions and enhance the transdermal permeability. These micropores are orders of magnitude larger than molecular dimensions, and, therefore, should readily permit the transport of hydrophilic macromolecules. Various strategies have been employed by many research groups and pharmaceutical companies worldwide, for the fabrication of MNs. This review details various types of MNs, fabrication methods and, importantly, investigations of clinical safety of MN. PMID- 20297913 TI - What application for what job? PMID- 20297914 TI - The Panther Pixy video jib. PMID- 20297915 TI - Team based review and reflection. PMID- 20297918 TI - Clinical photography: science or art? PMID- 20297920 TI - Establishment and characterization of a fibroblast line from landrace. AB - Up to 32 Landrace ear marginal tissue samples were used for establishing a fibroblast cell bank by the means of primary explantation and cryopreservation. Biological analysis suggested that the Population Doubling Time (PDT) of the cell line was approximately 24h. The diploid accounted for 97.2% of the whole population; isozyme analysis of Lactic Dehydrogenase (LDH) and Malic Dehydrogenase(MDH) disproved cross-contamination from other cell lines. The results of bacterium, fungus, virus and mycoplasma tests were all negative. The transfection rates of three fluorescent proteins were high, indicating that the exogenous genes could be effectively expressed in the cells. It had not only preserved the precious germplasm resource of the Landrace on the cell level but also provided valuable material for the researches of genomics, postgenomics, somatic cloning and so on. PMID- 20297919 TI - Immunosuppressive effects of triclosan, nonylphenol, and DDT on human natural killer cells in vitro. AB - Human natural killer (NK) cells are a first-line immune defense against tumor cells and virally-infected cells. If their function is impaired, it leaves an individual more susceptible to cancer development or viral infection. The ability of compounds that contaminate the environment to suppress the function of NK cells could contribute to the increased risk of cancer development. There are a wide spectrum of compounds that significantly contaminate water and food that are consumed by humans, leading to accumulation of some of these compounds in human tissues. In the current study, we examined the ability of three such compounds to diminish the function of human NK cells. Triclosan (TC) is an antimicrobial agent used in a large number of antibacterial soaps. Nonylphenol (NP) is a degradation product of compounds used as surfactants and as stabilizers in plastics. 4,4' Dichlorodiphenyltrichloroethane (DDT) is a pesticide that is mainly used to control mosquitoes. The compounds were examined for their ability to suppress NK function following exposures of 1 h, 24 h, 48 h, and 6 days. Each agent was able to substantially decrease NK lytic function within 24 h. At a concentration of 5 microM, both TC and NP inhibited NK lytic function by 87 and 30%, respectively; DDT decreased function by 55% at 2.5 microM. The negative effects of each of these compounds persisted and/or intensified following a brief (1 h) exposure to the compounds, indicating that the impairment of function cannot be eliminated by removal of the compound under in vitro conditions. PMID- 20297921 TI - Pretreatment with hemoglobin-based oxygen carriers protect isolated rat heart from myocardial infarction. AB - This study was designed to investigate whether polymerized human placenta hemoglobin (PolyPHb) pretreatment provided protection to the heart after ischemia/reperfusion (I/R) injury. After 10-min basal perfusion, isolated Sprague Dawley rat hearts were pretreated with 0.1 gHb/dL PolyPHb and subjected to I/R injury. PolyPHb pretreatment greatly reduced the decreases in left ventricular developed pressure (LVDP), maximum LVDP increase and decrease rate (+/-dp/dt), and the increase in left ventricular end-diastolic pressure (LVEDP) as compared to the control group. Moreover, the myocardial infarction and troponin-I release were significantly reduced in the pre-HBOCs group. Therefore, PolyPHb pretreatment was protective to the isolated I/R heart. PMID- 20297922 TI - Fiber optical spatial filter anemometry--intravital measurement of red blood flow velocity (RBCV) in the microcirculation. AB - The fiberoptical spatial filter anemometry (SFA) is a common technique based on an optical grid to measure the velocity of corpuscular components in a multiphase flow, e.g. in the microvessels. The technical innovation is the analysis of flow velocities using an optical grid sensor and frequency analysis by Fast Fourier Transformation (FFT). This study describes a non-invasive, on-line technique to measure RBCV in the microcirculation. The sensor's validity was proven by in vitro measurements using a rotation disk of an exactly defined velocity with a correlation coefficient of 0.99967. For validation of RBCV measurements in the microcirculation in vivo, the setup was adapted to an intravital microscope. RBCV was measured in arterioles, capillaries, and postcapillary venules ranging from 8 140 microm diameter. As reference method for velocity measurements a computer assisted imaging system was used to measure the RBC-velocity in the identical vessels by frame to frame analysis. Both methods revealed a high significant correlation using transillumination technique for capillaries (r=0.986, p<0.001) and venules (r=0.952, p<0.001) as well as epiillumination technique (capillaries r=0.939, venules r=0.975, p<0.001). PMID- 20297923 TI - Utility of the carboxylesterase inhibitor bis-para-nitrophenylphosphate (BNPP) in the plasma unbound fraction determination for a hydrolytically unstable amide derivative and agonist of the TGR5 receptor. AB - The potent, functional agonist of the bile acid Takeda G-protein-coupled receptor 5 (TGR5), (S)-1-(6-fluoro-2-methyl-3,4-dihydroquinolin-1(2H)-yl)-2-(isoquinolin-5 yloxy)ethanone (3), represents a useful tool to probe in vivo TGR5 pharmacology. Rapid degradation of 3 in both rat and mouse plasma, however, hindered the conduct of in vivo pharmacokinetic/pharmacodynamic investigations (including plasma-free fraction (f(u plasma)) determination) in rodent models of pharmacology. Studies were therefore initiated to understand the biochemical basis for plasma instability so that appropriate methodology could be implemented in in vivo pharmacology studies to prevent the breakdown of 3. Compound 3 underwent amide bond cleavage in both rat and mouse plasma with half-lives (T(1/2)) of 39 + or - 7 and 9.9 + or - 0.1 min. bis(p-nitrophenyl) phosphate (BNPP), a specific inhibitor of carboxylesterases, was found to inhibit hydrolytic cleavage in a time- and concentration-dependent manner, which suggested the involvement of carboxylesterases in the metabolism of 3. In contrast with the findings in rodents, 3 was resistant to hydrolytic cleavage in both dog and human plasma. The instability of 3 was also observed in rat and mouse liver microsomes. beta-Nicotinamide adenine dinucleotide phosphate, reduced form (NADPH)-dependent metabolism of 3 occurred more rapidly (T(1/2) approximately 2.22-6.4 min) compared with the metabolic component observed in the absence of the co-factor (T(1/2) approximately 89-130 min). Oxidative metabolism dominated the NADPH-dependent decline of 3, whereas NADPH-independent metabolism of 3 proceeded via simple amide bond hydrolysis. Compound 3 was highly bound (approximately 95%) to both dog and human plasmas. Rat and mouse plasma, pre treated with BNPP to inhibit carboxylesterases activity, were used to determine the f(u plasma) of 3. A BNPP concentration of 500 microM was determined to be optimal for these studies. Higher BNPP concentrations (1000 microM) appeared to displace 3 from its plasma protein-binding sites in preclinical species and human. Under the conditions of carboxylesterases-inhibited rat and mouse plasma, the level of protein binding displayed by 3 was similar to those observed in dog and human. In conclusion, a novel system has been devised to measure f(u plasma) for a plasma-labile compound. The BNPP methodology can be potentially applied to stabilize hydrolytic cleavage of structurally diverse carboxylesterase substrates in the plasma (and other tissue), thereby allowing the characterization of pharmacology studies on plasma-labile compounds if and when they emerge as hits in exploratory drug-discovery programmes. PMID- 20297924 TI - Guideline recommendations for long-term treatment of depression with antidepressants in primary care--a critical review. AB - BACKGROUND: Long-term treatment with antidepressants is considered effective in preventing recurrence of major depressive disorder (MDD). It is unclear whether this is true for primary care. OBJECTIVES: We investigated whether current guideline recommendations for long-term treatment with antidepressants in primary care are supported by evidence from primary care. METHODS: Data sources for studies on antidepressants: PubMed, Cochrane Library, Embase, PsycInfo, Cinahl, articles from reference lists, cited reference search. SELECTION CRITERIA: adults in primary care, continuation or maintenance treatment with antidepressants, with outcome relapse or recurrence, (randomized controlled) trial/naturalistic study/review. LIMITS: published before October 2009 in English. RESULTS: Thirteen depression guidelines were collected. These guidelines recommend continuation treatment with antidepressants after remission for all patients including patients from primary care, and maintenance treatment for those at high risk of recurrence. Recommendations vary for duration of treatment and definitions of high risk. We screened 804 literature records (title, abstract), and considered 27 full-text articles. Only two studies performed in primary care addressed the efficacy of antidepressants in the long-term treatment of recurrent MDD. A double blind RCT comparing mirtazapine (n = 99) and paroxetine (n = 98) prescribed for 24 weeks reported that in both groups 2 patients relapsed. An open study of 1031 patients receiving sertraline for 24 weeks, who were naturalistically followed-up for up to two years, revealed that adherent patients had a longer mean time to relapse. CONCLUSIONS: No RCTs addressing the efficacy of maintenance treatment with antidepressants as compared to placebo were performed in primary care. Recommendations on maintenance treatment with antidepressants in primary care cannot be considered evidence-based. PMID- 20297925 TI - Central nervous system tuberculomas in 23 patients. AB - Central nervous system tuberculomas are rare and severe complications of tuberculosis. We performed a retrospective study of the clinical, biological, radiological, pathological, and therapeutic features of 23 patients. Almost all patients were from countries with a high prevalence of tuberculosis (22/23). Their mean age was 37.3 y; 43.5% had laboratory-proven meningitis and 17.4% had biopsy-proven tuberculomas. For most of the patients, the duration of treatment lasted 13-18 months. The disease was controlled without relapse in 16 patients and 3 patients died. Diagnosis relies on magnetic resonance imaging and bacteriological specimens from all the involved sites. This study indicates that central nervous system tuberculomas occur in young patients from high risk countries. The anti-tuberculous drug regimen in this series was 2 months of isoniazid, rifampin, pyrazinamide and ethambutol, followed by at least 10 months of isoniazid and rifampin. Results did not contradict the use of a 12-month regimen as currently recommended. PMID- 20297926 TI - Lack of hygiene routines among patients and family members at patient hotels--a possible route for transmitting puerperal fever. AB - The use of patient hotels for ambulatory care of women with uncomplicated deliveries has become a routine in Sweden. This report describes a minor outbreak of a group A Streptococcus strain in 2 newly delivered mothers and their newborn babies at a patient hotel. PMID- 20297927 TI - Imported melioidosis in Danish travellers: a diagnostic challenge. AB - Infections with Burkholderia pseudomallei (melioidosis) are rare events in Scandinavian countries, but the bacterium may be contracted during travel to endemic areas, i.e. Southeast Asia (especially Thailand) and northern Australia. Here, 5 travel-related cases occurring within the last 3 y in Denmark are reported, with particular emphasis on diagnostic and therapeutic challenges posed to health staff with little experience in the management of melioidosis. A newly developed B. pseudomallei-specific polymerase chain reaction test was applied and was able to correctly identify all isolates. PMID- 20297928 TI - Long-term follow-up of patients with posterior canal benign paroxysmal positional vertigo. AB - CONCLUSIONS: Recurrence of posterior canal benign paroxysmal positional vertigo (PC-BPPV) developed in one-third of patients when followed for an average of 5 years from diagnosis. History of head trauma and Meniere's disease contributed significantly to recurrence (p < 0.05). History of head trauma as an etiologic cause was more frequent in patients with recurrence of PC-BPPV. OBJECTIVES: To estimate recurrence in the long-term follow-up of patients with PC-BPPV after successful canalith repositioning maneuvers, and to determine which factors contribute to recurrence. METHODS: The charts of 118 patients with PC-BPPV were reviewed. Data of patients were recorded from the initial evaluation and treatment. Follow-up was performed at mean of 64 +/- 7.7 months after the initial phase. The Dix-Hallpike maneuver was performed for diagnosis, and all patients were treated by the canalith repositioning maneuver, which was repeated every 3 days until the patients were symptom-free or results of the Dix-Hallpike maneuver were negative. RESULTS: At diagnosis, the most common etiology was idiopathic in 55 patients (46.6%). Recurrence occurred in 39 of 118 patients (33.1%). Recurrence occurred within the first 2 years in 21 of the 39 patients (53.8%). History of head trauma was a more frequent finding in patients who developed recurrence (12 of 39, 30.8%). PMID- 20297929 TI - Acute idiopathic sensorineural hearing impairment at frequency exceeding 8 kHz. AB - CONCLUSIONS: Acute idiopathic sensorineural hearing impairment at a frequency exceeding 8 kHz (high-frequency range) was recognized in patients suffering from acute tinnitus without hearing loss. The cases in this study may contribute to clarifying the pathogenesis of tinnitus without hearing loss and evaluating its response to steroid therapy. OBJECTIVES: The aim of this study was to demonstrate the existence of acute idiopathic sensorineural hearing impairment only in the high-frequency range and to investigate its relation to tinnitus without hearing loss. METHODS: Five patients aged 29 years or younger who consulted a hospital within a few days after the onset of unilateral tinnitus without hearing loss were studied. We conducted audiometry involving the high-frequency range on first medical examination and on improvement in tinnitus, and investigated the association between the hearing findings in the high-frequency range and a tinnitus prognosis. RESULTS: All five patients showed abnormalities in the threshold in the high-frequency range on the affected side. In the three cases given prednisolone, tinnitus and the threshold abnormalities were reduced within 20 days. In contrast, tinnitus and the threshold abnormalities showed little change in two patients who were not treated. PMID- 20297931 TI - Flow cytometric assessment of glycoprotein movements in platelets. PMID- 20297930 TI - Cytokines, platelet production and hemostasis. AB - A number of hematopoietic growth factors and other cytokines are capable of altering platelet production and function. Enhancement of these processes may be exploited to ameliorate bleeding propensity in thrombocytopenic patients. Under certain circumstances, cytokines may have adverse effects on the hemostatic system, potentially involved in thrombogenesis and atherogenesis. Inhibition of those cytokines may prove to be a useful experimental approach to investigate their potential pathophysiologic role. PMID- 20297932 TI - Scott syndrome: an inherited defect of the procoagulant activity of platelets. AB - Anionic phospholipids, chiefly phosphatidylserine, are essential for the assembly of the characteristic enzyme complexes of the blood coagulation cascade at the surface of stimulated platelets and derived microparticles. In the resting cell, these phospholipids are sequestered in the inner leaflet of the plasma membrane. Scott syndrome is an extremely rare bleeding disorder that confirms the essential role of these anionic procoagulant phospholipids. In Scott patients, phosphatidylserine externalization and microparticle shedding are dramatically impaired. This functional deficiency is clearly evidenced by the measurement of residual prothrombin in serum. The recent detection of a familial Scott syndrome testifies to the genetic origin of the defect. Symptomatic Scott patients present provoked hemorrhages and are probably homozygous for the disorder whereas asymptomatic children are probably heterozygous. The Scott phenotype can be detected in platelets, red cells and lymphocytes by functional prothrombinase assay and flow cytometry. Intermediate degrees of phosphatidylserine exposure and vesiculation are observed in cells from the asymptomatic heterozygous offspring when compared to those from their homozygous defective parent and healthy subjects. The functional and molecular characterization of mutated element(s) in Scott syndrome should be of valuable help for the understanding of phospholipid transmembrane migration, also termed flip-flop, its possible links with membrane vesiculation, and the eventual implications in thrombotic or apoptotic processes. PMID- 20297933 TI - Abnormalities in platelet membrane structure and function in Alzheimer's disease and ischaemic stroke. PMID- 20297934 TI - Signal transduction in the platelet activation induced by IgG anti-streptokinase and anisoylated plasminogen-streptokinase activator complex. AB - Streptokinase (SK) is one of the plasminogen activators currently used in therapeutics. SK antibodies may appear in the blood after thrombolytic therapy with SK or after ss-hemolytic streptococci infection. Such antibodies may both activate platelets and neutralize the ability of SK to convert plasminogen into plasmin. We previously demonstrated that platelet activation induced by the combination of IgG anti-SK and anisoylated plasminogen-SK activator complex (APSAC) is mediated by Fgamma7RIIal receptor. However, the mechanism by which IgG anti-SK and APSAC (or SK) transduce an activating signal across the platelet plasma membrane remains unknown. We have demonstrated in the present study that the platelet aggregation induced by the combination of IgG anti-SK and APSAC is accompanied by an increase in inositol phosphate, Ca(2+) mobilization and thromboxane (Tx) A2 generation. Neomycin, erbstatin and GF 109203X, which inhibit phospholipase C (PLC), protein tyrosine kinase (PTK) and protein kinase C (PKC) activities, respectively, abolished platelet aggregation induced by IgG anti-SK plus APSAC, indicating the pivotal roles of the PLC, PTK and PKC pathways in this immunological activation. In addition, TxA2 generation is also important since aspirin, a cyclo-oxygenase inhibitor and SQ 29548, a TxA2 receptor antagonist, showed significant inhibition of the platelet response. The contribution of released ADP was confirmed using apyrase, which significantly inhibited IgG anti SK plus APSAC-induced platelet aggregation. Finally, WEB 2086, a platelet activating factor (PAF) receptor antagonist, was not effective, indicating that PAF is not involved in this process. APSAC- or SK-induced platelet activation may limit the therapeutic effectiveness of the drug and may contribute to the pathogenesis of early reocclusion. The study of the mechanism leading to APSAC induced platelet activation could be relevant for a better understanding of the physiopathology of immune complex disorder diseases and thrombolytic treatment failure. PMID- 20297935 TI - Differential formation of a bioactive antiaggregating substance (BAS) by layers of the vein wall. AB - Human umbilical veins were analyzed with and without endothelium in order to study the ability of endothelial cells and subendothelium to release a bioactive anti-aggregating substance (BAS: MW > 30kDa) independent of prostacyclin (PGI(2)). To evaluate the role of the subendothelium, the endothelial cells were removed by rubbing on filter paper for 1 min. We performed a histopathological study of the vessels using hematoxylin and eosine, and stained for elastic tissue fibers in order to confirm the presence of endothelium. The supernatant from incubated vascular rings was partially purified by Sephadex G-50 to rule out PGI(2). The void volume fractions were collected and the anti-aggregating activity was tested on platelet aggregation induced by arachidonic acid, ADP, collagen and epinephrine. We observed that the activity was taking place with the use of the intact endothelium while there was no activity in the denuded vein. These observations could help to explain the well known antithrombotic properties of vascular endothelium. PMID- 20297936 TI - Regulation of PAF-induced platelet responses by cyclic nucleotides. AB - The existence of cross-talk mechanisms between the cyclic nucleotide system and other transduction systems involved in PAF-activated platelets is described in this study. A protein of 125 kDa, identified as pp 125(FAK), is tyrosine phosphorylated by PAF in a time- and concentration-dependent manner. The presence of a cAMP- or a cGMP-elevating agent, used alone or in combination, together with PAF diminished tyrosine phosphorylation. The sensitivity to cAMP shown by PAF induced ppl25 phosphorylation on tyrosine residues was similar to PAF-induced phosphorylation of a 47-kDa protein (pp47) on serine and threonine. In contrast, the latter was not affected in the presence of a cGMP-elevating agent, although it was able to enhance synergistically the inhibitory effect of forskolin. Data reported herein also show that pp47 phosphorylation and serotonin secretion are not closely correlated. Accordingly, sodium nitroprusside (SNP) did not have any effect on phosphorylation of pp47, but it was able to inhibit serotonin secretion when added alone, and it showed a synergistic inhibitory action with forskolin. PMID- 20297937 TI - Persistence of low platelet adhesiveness in von Willebrand disease during pregnancy. AB - Platelet adhesiveness (PA) is a valuable measure of ex vivo platelet function. A low PA is a usual feature of von Willebrand disease (vWd). However, PA has rarely been measured during vWd pregnancies. The aim of this work was to observe the behaviour of PA in vWd pregnancies. PA was measured during pregnancy in 33 vWd patients. Intrapregnancy PA remained low without any significant variation compared with non-pregnancy values. Advanced gestation was not accompanied by any increase in PA in spite of the concomitant normalization showed by the other markers of vWd. A low intrapregnancy value was not predictive of an increased risk of bleeding at labour. A low PA could be the only clue for vWd during gestation warranting both a vigilant postpartum attitude and a thorough haemostatic evaluation after pregnancy. PMID- 20297938 TI - Soluble P-selectin assay: importance of correct anticoagulant choice. AB - P-selectin is stored preformed in the alpha-granules of platelets. Previous studies show ss-thromboglobulin, also stored in alpha-granules can be readily released from platelets during the processing of whole blood. This artefactual release was rectified by using combination of various anti-platelet and anticoagulant compounds placed in the collecting tube. We investigated the levels of sP-selectin from 40 volunteers, comparing two anticoagulants, tri-sodium citrate, CTAD (a mixture of sodium citrate and citric acid, theophylline, adenosine and dipyridamole) plus iloprost and serum. Iloprost, a stable prostacyclin analogue, is a potent anti-platelet agent. We found significantly lower levels of sP-selectin (P< 0.0001, paired t-test) measured from blood collected into CTAD and iloprost compared to levels measured from either citrated plasma or serum. We suggest that plasma levels obtained from the blood collected into a CTAD tube containing iloprost are likely to more accurately reflect the true levels of circulating sP-selectin than those obtained when test-tube activation of platelets is allowed to continue in vitro. PMID- 20297939 TI - Differential effects of native and oxidatively modified low-density lipoproteins on platelet function. AB - Low-density lipoproteins (LDL) have been various reported to induce platelet aggregation independently and/or sensitise platelets to other agonists. In these earlier studies the extent of oxidation of LDL was not always reported or addressed. We have now investigated the effects of native, minimally modified and fully oxidised LDL (0-1gapolipoproteinB(100)/l on platelet function using platelet aggregometry and fluorescence activated flow cytometry. Native LDL did not activate isolated platelets but inhibited ADP- and thrombin-induced aggregation of isolated platelets by 51 % in the presence or absence of added fibrinogen. Longer pre-incubations were required to produce a comparable inhibition by native LDL on platelets in plasma. Flow cytometric analysis showed that native LDL inhibited ADP-induced fibrinogen binding by up to 38%. In contrast, minimally modified LDL induced primary platelet aggregation and fibrinogen binding in the absence of other agonists, enhanced both submaximal (1 2mumol/l) ADP-induced aggregation, fibrinogen binding and degranulation (CD63 and P-selectin expression). Fully oxidised LDL, however, inhibited ADP-induced platelet aggregation and fibrinogen binding. The effects of minimally modified LDL on platelet aggregation could be reproduced partially by adding 15 hydroperoxy-eicosatetraenoic acid to native LDL. These data indicate that the extent of oxidation of LDL is critical in determining their effects on platelet function. Native LDL did not activate platelets, whilst minimally modified LDL exerted a pro-aggregatory effect, possibly due to the presence of lipid hydroperoxides near to the concentration range found in pathological states. PMID- 20297940 TI - The H(1)-histamine antagonist dithiaden inhibits human platelet function in vitro. AB - The H(1)-histamine receptor antagonist Dithaden(R) inhibited in a dose-dependent manner, human platelet aggregation in vitro that was induced with stimuli in the following rank order of potency: thrombin > A23187 > adrenaline > ADP. The aggregation of platelets in plasma induced with adrenaline was inhibited by Dithiaden (DIT) (both the first and the second phase) and the onset of the second phase was prolonged significantly. In a concentration-dependent manner DIT inhibited thrombin- and calcium ionophore A23187-induced [(3)H]arachi-donic acid liberation from, and peroxidation (measured as malondialdehyde formation) of membrane phospholipids. The same effect of DIT was found for the inhibition of thromboxane B(2) generation. It is suggested that DIT does not inhibit stimulated platelets at specific histamine receptors sites but rather at the phospholipase A(2) and thromboxane synthase level. Results from in vitro experiments should be verified in vivo. PMID- 20297941 TI - Lysophosphatidic acid induces protein tyrosine phosphorylation in the absence of phospholipase C activation in human platelets. AB - Lysophosphatidic acid is a biologically active phospholipid able to induce cell proliferation and platelet aggregation. In this study we investigated the biochemical mechanisms of platelet activation by lysophosphatidic acid. We found that lysophosphatidic acid stimulated the binding of the photoreactive GTP-analog 4-azidoanilido-[alpha(32)P]GTP to a 40-kDa protein on platelet membranes. Moreover, lysophosphatidic acid induced the rapid decrease of the intracellular concentration of cAMP in intact platelets, indicating that this lipid activates platelets by binding to a membrane receptor coupled to the inhibitory GTP-binding protein Gi. In agreement with a receptor-mediated action, we found that platelet activation by lysophosphatidic acid underwent homologous desensitization. In the absence of extracellular CaCl(2), lysophosphatidic acid did not induce platelet aggregation, and did not stimulate phospholipase C. However, under the same conditions, lysophosphatidic acid produced the rapid tyrosine phosphorylation of several platelet proteins. This effect was not mediated by the formation of thromboxane A(2). Our results demonstrate that, in lysophosphatidic acid stimulated platelets, activation of protein-tyrosine kinases occurs in the absence of phospholipase C activation and platelet aggregation, and may be directly related to the activation of the G-protein-coupled lysophosphatidic acid receptor. PMID- 20297942 TI - 'ADP-induced binding of fibrinogen to activated platelets is rapid and parallels platelet microaggregation'. PMID- 20297943 TI - Erratum. PMID- 20297944 TI - A study of outcome in patients treated at a psychiatric emergency unit. AB - BACKGROUND: Although being an important part of the psychiatric treatment chain, there are few outcome studies of treatment at psychiatric emergency units (PEU). AIMS: The aim was to measure changes in psychopathology and humiliation during admission at a PEU. METHODS: The sample consisted of 147 patients examined at admission and discharge. The instruments used were the Brief Psychiatric Rating Scale (BPRS), the Narcissistic Personality Inventory-29 (NPI-29), the Hospital Anxiety and Depression Scale (HADS), a combination of questions measuring negative experiences and Cantril's ladder measuring experienced humiliation. Outcome measures were clinically significant improvement [>10% reduction of the BPRS converted (0-100) score] and changes on the other instruments. RESULTS: Median hospitalization time was 13 days (mean 20.4 days). Fifty-six per cent of the patients showed clinical significant improvement (95% CI 48-64%), 42% showed some degree of improvement and 2% were unchanged. The more improved patients had higher scores at admission than those with less improvement on all scales, indicating a floor effect. Small changes were observed for narcissism and experienced humiliation and negative admission events. In multivariate analyses high admission scores on BPRS subscales, thinking disorder and activation and HADS total score were significantly associated with clinically significant improvement. Type and length of admission did not significantly affect the outcome. The BPRS, HADS and NPI-29 scores at discharge were mainly explained by corresponding admission scores. CONCLUSIONS: More than half the patients admitted to PEU have clinically significant reduction of psychopathology during their stay. Higher levels of psychopathology at admission were significantly associated with improvement. Negative admission experiences and involuntary admission did not influence outcome. PMID- 20297945 TI - Disulfiram in severe alcoholism--an open controlled study. AB - BACKGROUND: Disulfiram is used to a great extent in Denmark to treat alcoholism but the evidence is limited. AIM: To study the effect of supervised disulfiram treatment in alcohol dependence. Subjects were recruited from a psychiatric emergency ward following alcohol withdrawal treatment. METHODS: A total of n=39 patients were openly randomized to either disulfiram 800 mg twice a week for 26 weeks (n=19) or no disulfiram (n=20). All patients were also treated with cognitive behavioural therapy (CBT) in groups. RESULTS: The rate of abstinence was 20% and 26% in the control and disulfiram group, respectively. This difference was not statistically significant (NS). A trend towards increased mean time to first drink was found in the disulfiram group (96 vs. 76 days in the control group, NS), while fewer patients in this group completed CBT group therapy (41% vs. 67% in the control group, NS). Alcohol-free days were 100 days in both groups (NS). CONCLUSION: Supervised disulfiram administration did not have any major impact on the treatment outcome. PMID- 20297946 TI - Efficient and gentle siRNA delivery by magnetofection. AB - Magnetic force combined with magnetic nanoparticles recently has shown potential for enhancing nucleic acid delivery. Achieving effective siRNA delivery into primary cultured cells is challenging. We compared the utility of magnetofection with lipofection procedures for siRNA delivery to primary and immortalized mammalian fibroblasts. Transfection efficiency and cell viability were analyzed by flow cytometry and effects of gene knockdown were quantified by real-time PCR. Lipofectamine 2000 and magnetofection achieved high transfection efficiencies comparable to similar gene silencing effects of about 80%; the cytotoxic effect of magnetofection, however, was significantly less. Magnetofection is a reliable and gentle alternative method with low cytotoxicity for siRNA delivery into difficult to transfect cells such as mammalian fibroblasts. These features are especially advantageous for functional end point analyses of gene silencing, e.g., on the metabolite level. PMID- 20297948 TI - Antifungal susceptibility, serotyping, and genotyping of clinical Cryptococcus neoformans isolates collected during 18 years in a single institution in Madrid, Spain. AB - We studied the serotypes, mating-types, AFLP genotypes, and antifungal susceptibility of 58 Cryptococcus neoformans strains causing 56 episodes of cryptococcosis in 55 patients over an 18-year period in a single institution. The underlying conditions of the patients were classified as HIV infection (n = 48) or non-HIV-related immunodeficiency (n = 7). Serotype A (n = 34; 58.9%) predominated, but serotype AD was involved in 23.2% of episodes. Most of the episodes were caused by mating-type alpha (n = 41; 73.2%) or alpha/a strains (n = 12; 21.5%). The most common genotype was AFLP1 (n = 26; 44.8%), followed by AFLP3 (n = 21; 36.2%), and AFLP2 (n = 11; 19.0%). In two different patients, we showed the coexistence of different serotypes and/or genotypes in the same episode (AFLP1 and 3). The new triazoles voriconazole, posaconazole and isavuconazole showed high and similar antifungal activity (MICs <= 0.125 MUg/ml). Fluconazole also had good antifungal activity, but two strains from patients with HIV infections had an MIC of 16 MUg/ml (3.4%). However, these two isolates remained very susceptible to the new triazoles (MICs <= 0.062 MUg/ml). The remaining strains always showed MICs <= 8 MUg/ml. PMID- 20297949 TI - Epidemiology and risk factors for dermatophytoses in rabbit farms. AB - While dermatophytoses of several animal species have been extensively investigated, information on their occurrence and epidemiology in rabbits is limited. We carried out a study from October 2006 to February 2007 of 23 rabbit farms in Apulia and Basilicata regions (southern Italy) in order to investigate the occurrence and risk factors associated with dermatophytoses in breeding rabbits. Dermatophytes were isolated from 86.9% (20/23) of the farms and from 51.8% (420/810) of the animals sampled. Trichophyton mentagrophytes (47.9%) and Microsporum canis (3.2%) were isolated from diseased (71.7%) and healthy (48.4%) animals as well from the surrounding environment (7.5%). The occurrence of lesions, the age of rabbits, and farm management (e.g., temperature, humidity and methods and frequency of disinfection practices) were identified as the most significant risk factors (P < 0.05) for the occurrence of dermatophytes. Animals in fattening and finishing stages were the most frequently infected (i.e., 58.2 and 61.6% respectively). Dermatophyte prevalence was significantly (P < 0.05) higher in areas with higher temperature (>20 degrees C) and relative humidity ranging from 62-65%. The results of the present investigation suggest that zoonotic dermathophytes are present in rabbit farms and highlight the importance of correct management procedures for the control of the infections. PMID- 20297950 TI - Proof of concept study: does fenofibrate have a role in sleep apnoea syndrome? AB - OBJECTIVE: To investigate the effect of fenofibrate on sleep apnoea indices. METHODS: Proof-of-concept study comprising a placebo run-in period (1 week, 5 weeks if fibrate washout was required) and a 4-week randomized, double-blind treatment period. Thirty-four subjects (mean age 55 years, body mass index 34 kg/m 2 , fasting triglycerides 3.5 mmol/L) with diagnosed sleep apnoea syndrome not treated with continuous positive airways pressure were enrolled and randomized to once daily treatment with fenofibrate (145 mg NanoCrystal(R) tablet) or placebo. Overnight polysomnography, computerized attention/vigilance tests and blood sampling for measurement of lipids, insulin, fasting plasma glucose and fibrinogen were performed at the end of each study period. CLINICAL TRIAL REGISTRATION: NCT00816829. MAIN OUTCOME MEASURES: As this was an exploratory study, a range of sleep variables were evaluated. The apnoea/hypopnoea index (AHI) and percentage of time spent with arterial oxygen saturation (SpO(2)) <90% were relevant as they have been evaluated in other clinical trials. Other variables included total apnoeas, hypopnoeas and oxygen desaturations, and non-cortical micro-awakenings related to respiratory events per hour. RESULTS: Fenofibrate treatment significantly reduced the percentage of time with SpO(2) <90% (from 9.0% to 3.5% vs. 10.0% to 11.5% with placebo, p = 0.007), although there was no significant change in the AHI (reduction vs. control 14% (95%CI -47 to 40%, p = 0.533). Treatment reduced obstructive apnoeas (by 44%, from 18.5 at baseline to 15.0 at end of treatment vs. 29.0 to 30.5 on placebo, p = 0.048), and non-cortical micro-awakenings per hour (from 23.5 to 18.0 vs. 24.0 to 25.0 with placebo, p = 0.004). Other sleep variables were not significantly influenced by fenofibrate. KEY LIMITATIONS: Exploratory study in patients with mild to moderate sleep apnoea, limited treatment duration; concomitant hypnotic treatment (35%); lack of correction for multiplicity of testing. CONCLUSIONS: The consistent direction of change in sleep indices in this proof-of-concept study may support further investigation of fenofibrate in moderate to severe sleep apnoea syndrome. PMID- 20297951 TI - Healthcare expenditure in severely depressed patients treated with escitalopram, generic SSRIs or venlafaxine in the UK. AB - OBJECTIVE: To retrospectively compare the 12-month healthcare utilisation and direct medical costs associated with the use of escitalopram, generic SSRIs, and venlafaxine in patients with severe depression in the United Kingdom (UK). METHODS: Data for this retrospective cohort study were extracted from the GPRD, a large primary care database in the UK. Data from adults with an incident prescription of escitalopram, venlafaxine, or generic SSRI were extracted. The initial prescription had to fall within 3 months of a physician visit when severe depression according to the GPRD definition was mentioned. Frequency of antidepressant treatment, GP consultations, referrals, hospitalisations, and concomitant psychiatric medication was assessed on the 12-months after initial prescription and 2006 unit costs for healthcare services obtained from published literature were applied, and then compared between treatment cohorts using a propensity score-adjusted generalised linear model. RESULTS: The total annual healthcare expenditure per patient was similar with escitalopram and generic SSRIs (916 pounds vs. 974 pounds, adjusted p = 0.48) and significantly lower than venlafaxine (916 pounds vs. 1367 pounds, adjusted p < 0.0001), a pattern repeated when antidepressant costs were excluded from the analysis (escitalopram vs. SSRIs, 831 pounds vs. 957 pounds, adjusted p = 0.10; escitalopram vs. venlafaxine, 831 pounds vs. 1156 pounds, adjusted p = 0.006). Over the 12-month analysis period, there were significantly fewer hospitalisations per patient in the escitalopram vs. venlafaxine (0.12 vs. 0.27; adjusted p = 0.01) or generic SSRI (0.12 vs. 0.19; adjusted p = 0.046) groups. CONCLUSION: Despite some limitations associated with the system of data collection in the GPRD (need to apply proxies for severity assessment and external unit costs to resource consumption), the results of this real-life study brings additional evidence of escitalopram appearing to be a cost-effective treatment for patients suffering from severe depression as diagnosed in routine practice and could be considered for first-line treatment in these patients. PMID- 20297952 TI - Clinical evaluation of combined therapy for type 2 diabetes. AB - OBJECTIVE: Therapeutic guidelines recommend the combination of drugs as necessary to control type 2 diabetes (T2D). This research assessed the effectiveness of pioglitazone (Pio), metformin (Met) and sulfonylurea (SU) combinations in the routine clinical practice. RESEARCH DESIGN AND METHODS: A nationwide, 12-month prospective, observational cohort study was performed in 2294 patients with T2D (50.3% females, mean age: 61.1 years, mean body mass index: 30.2 kg/m(2), mean time since diagnosis: 8.5 years) who started, at the discretion of treating physician, oral antihyperglycaemic treatment with either Pio + SU, Pio + Met or SU + Met because of inadequate control with previous therapy. Fasting plasma glucose (FPG), glycohaemoglobin (HbA1c), lipids, blood pressure, and anthropometric parameters were measured, and 10-year cardiovascular risk was estimated. RESULTS: FPG, HbA1c and total cholesterol at baseline had mean values (184.6 mg/dl, 8.5% and 246.0 mg/dl, respectively) associated with an excess of micro- and macrovascular risk. The mean changes from baseline in the Pio + SU, Pio + Met and SU + Met cohorts were, respectively, -37.9, -32.7 and -25.8 mg/dl for FPG; -1.1, -1.0 and -0.7% for HbA1c; -30.7, -38.7 and -17.1 mg/dl for triglycerides; and +2.3, +2.5 and +0.6 mg/dl for HDL cholesterol. In consequence, the estimated 10-year cardiovascular risk decreased more in the Pio cohorts, particularly with Pio + Met (1.7% versus 1.4% Pio + SU and 1.0% SU + Met Framingham equation- and 0.6% versus 0.4% SU + Met - Systematic Coronary Risk Evaluation model-). Related adverse events were significantly (p = 0.016) more frequent in Pio cohorts (4.7% with Pio + SU, 5.1% with Pio + Met) than in the SU + Met cohort (2.4%). CONCLUSIONS: In patients with T2D failing therapy, mostly SU or Met monotherapy, pioglitazone add-on treatment was associated with a significant improvement of micro- and macrovascular risk estimations. These results from real-life clinical conditions support the findings of prior randomised trials, although they should be interpreted with caution because of the observational, nonrandomised design. PMID- 20297955 TI - Mixed infections and the evolution of virulence: effects of resource competition, parasite plasticity, and impaired host immunity. AB - Mixed-genotype parasite infections are common in nature. Theoretical studies analyze the effects of such infections over evolutionary time and predict an increase in virulence due to the competitive advantage of virulent parasites. In contrast, experimental studies compare the overall virulence of mixed and single infections within one generation. Although these within-generation comparisons have limited relevance to existing theory, they demonstrate that within-host parasite interactions are not restricted to competition for resources, as envisaged by theory. Instead, mixed infections may result in phenotypic changes in growth rate or impaired immune clearance. Developing and using a two-parasite epidemiological model with recovery, we confirm that within-host competition for resources selects for higher virulence. However, parasite phenotypic plasticity and impaired host immunity can select for lower virulence. Because these latter two mechanisms would be detected by experimentalists as an increase in pathology, our results warn against the temptation to draw inferences on virulence evolution on the basis of single-generation experiments. PMID- 20298108 TI - Vitamin A supplementation in late pregnancy can decrease the incidence of bronchopulmonary dysplasia in newborns. AB - Bronchopulmonary dysplasia (BPD) is a chronic lung disease of infancy which is associated with prematurity and early lung injury resulting from mechanical ventilation. Oxygen toxicity, barotrauma, and volutrauma play key roles in its pathogenesis. Parenteral administration of Vitamin A to the newborn is the current recommended preventive therapy for BPD. Vitamin A has been found to upregulate genes necessary for fetal lung growth and increase surfactant production in animal models. Supplementation of Vitamin A in late pregnancy increases the cord blood vitamin A levels proportionately. Hence, we hypothesize that Vitamin A supplementation during late pregnancy can decrease the incidence of BPD in newborns. This can be an effective adjunct to postnatal preventive therapy. Vitamin A supplementation in late pregnancy carries no risk of teratogenicity unlike in early pregnancy. Moreover, vitamin A deficiency in pregnancy is associated with depressed immune function leading on to increased infectious morbidity and can cause intrauterine growth retardation, low birth weight and anemia in newborns. Combining antenatal Vitamin A supplementation to the mother with postnatal supplementation to the newborn can effectively prevent BPD better than the traditional postnatal preventive therapy alone. It will also treat the highly prevalent vitamin A deficiency in pregnant mothers and newborns of the developing world. PMID- 20297953 TI - Incidence of malignancies in HIV-infected patients and prognostic role of current CD4 cell count: evidence from a large Italian cohort study. AB - The incidence of and predictors of acquired immunodeficiency syndrome-defining malignancies (ADMs) and non-ADM (NADMs) were evaluated in a large Italian cohort. The incidence of ADM and NADM was 5.0 cases per 1000 person-years of follow-up (95% confidence interval, 4.3-5.8 cases per 1000 person-years of follow-up) and 2.4 cases per 1000 person-years of follow-up (95% confidence interval, 1.9-3.1 cases per 1000 person-years of follow-up), respectively. Lower current CD4 cell count was an independent predictor of developing malignancies, with the association being stronger for ADM than for NADM. PMID- 20298111 TI - Reduced-risk management of Rhagoletis cerasi flies (host race Prunus) in combination with a preliminary phenological model. AB - Seasonal flight activity of Rhagoletis cerasi (L.) (Diptera: Tephritidae) adults was monitored using yellow sticky traps at sweet cherry orchards under different management regimes in Bursa, northwestern Turkey, during 1997-1998. In the reduced-risk backyard orchards, soil ploughing in the fall or spring to destroy the pupae was combined with a single application of an insecticide, while conventionally managed orchards received six to seven insecticide applications for controlling adults. Traps in commercial orchards caught significantly fewer adults than those in reduced-risk backyard orchards. Levels of cherry fruit fly fruit damage were very low (0.1%) in commercial orchards, whereas infestation rates averaged 2.2% in reduced-risk orchards. A preliminary phenology model was developed for optimal timing of insecticide applications based on air temperature summations since 1 February. In the reduced-risk backyard orchards, the first flies were captured between 25 May and 2 June, corresponding to an average degree day (DD) accumulation of 582.50 +/- 10.50 DD at an altitude of 150 m. However, first adult emergence at 1170 m was recorded between 6 and 14 June, averaging 667.50 +/- 14.50 DD. Adult emergence exhibited bimodal peaks in a single flight at low altitude but there was a single peak at high altitude sites. Total adult flight period averaged 459 +/- 29.50 and 649 +/- 25.50 DD at low and high altitude sites, respectively. Our prediction model suggests that the optimum spray-window for a single insecticide application occurs between 577.70 and 639.40 DD at 150 m and between 780.90 and 848.60 DD at 1170 m. PMID- 20298109 TI - Resistance status of the Colorado potato beetle, Leptinotarsa decemlineata, to endosulfan in East Azarbaijan and Ardabil provinces of Iran. AB - Three Colorado potato beetle, Leptinotarsa decemlineata, populations, from Ardabil, Bostanabaad and Ajabshir, were collected from potato fields in East Azarbaijan and Ardabil provinces in Iran and assayed for resistance to endosulfan. Possible resistance mechanisms were investigated using synergism studies and biochemical assays. Laboratory tests showed that the Bostanabaad strain was 220 and 109 times resistant compared with the susceptible strain in 2003 and 2004, respectively. The resistance ratios for the Ajabshir and Ardabil strains were 19 and 18, respectively. Since considerably more resistance was observed in the Bostanabaad strain compared with the other two, further investigation of the origin of resistance was done on this strain. Two insecticide synergists, piperonyl butoxide and S,S,S-tributylphosphorotrithioate, reduced resistance 2.3 and 3.5 times, respectively. These small degrees of synergism suggest that metabolism is not the source of the considerable difference in susceptibility between the two strains. This was supported by the results obtained from the biochemical assays that showed that glutathione S transferase activity in the Bostanabaad strain did not significantly differ from the susceptible strain. These results suggest that target site insensitivity may be involved. PMID- 20298112 TI - Larval survival of fuller's rose weevil, Naupactus cervinus, on common groundcover species in orchards of New Zealand kiwifruit. AB - Fuller's rose weevil, Naupactus cervinus (Boheman) (Curculionidae: Entiminae), is an important quarantine pest of New Zealand kiwifruit exported to Asian markets. Both adults and larvae are considered to be polyphagous. In this study, the survival of larval N. cervinus was estimated on common groundcover species of kiwifruit (Actinidia spp.) in the Bay of Plenty, the main region in New Zealand where kiwifruit is grown. The botanical composition of groundcover in commercial kiwifruit orchards, characterised by survey, was dominated by ryegrass (Lolium perenne), with white clover (Trifolium repens), creeping buttercup (Ranunculus repens), wild strawberry (Duchesnea indica) and broadleaf dock (Rumex obtusifolius) in lower abundance. Survival to mature larvae or adult was relatively low (.11%) for N. cervinus introduced as neonates to field plots or potted ryegrass, white clover and broadleaf dock. White clover was a more favourable host for survival to adults than ryegrass. This study suggests that increased survival of N. cervinus larvae may occur where white clover and large dock plants are abundant, but that survival is likely to be highly variable because of the heterogeneous availability of preferred host plants and host plant quality. These data suggest that larval polyphagy is a strategy that enables N. cervinus to persist at low densities in kiwifruit orchards despite variation in the quality and diversity of groundcover. PMID- 20298113 TI - Onion thrips, Thrips tabaci, have gut bacteria that are closely related to the symbionts of the western flower thrips, Frankliniella occidentalis. AB - It has been shown that many insects have Enterobacteriaceae bacteria in their gut system. The western flower thrips, Frankliniella occidentalis Pergande [Thysanoptera: Thripidae], has a symbiotic relation with Erwinia species gut bacteria. To determine if other Thripidae species have similar bacterial symbionts, the onion thrips, Thrips tabaci, was studied because, like F. occidentalis, it is phytophagous. Contrary to F. occidentalis, T. tabaci is endemic in Europe and biotypes have been described. Bacteria were isolated from the majority of populations and biotypes of T. tabaci examined. Bacteria were present in high numbers in most individuals of the populations studied. Like F. occidentalis, T. tabaci contained one type of bacterium that clearly outnumbered all other types present in the gut. This bacterium was identified as an Erwinia species, as was also the case for F. occidentalis. However, its biochemical characteristics and 16S rDNA sequence differed from the bacteria present in F. occidentalis. PMID- 20298114 TI - Extensive natural intraspecific variation in stoichiometric (C:N:p) composition in two terrestrial insect species. AB - Heterotrophic organisms must obtain essential elements in sufficient quantities from their food. Because plants naturally exhibit extensive variation in their elemental content, it is important to quantify the within-species stoichiometric variation of consumers. If extensive stoichiometric variation exists, it may help explain consumer variation in life-history strategy and fitness. To date, however, research on stoichiometric variation has focused on interspecific differences and assumed minimal intraspecific differences. Here this assumption is tested. Natural variation is quantified in body stoichiometry of two terrestrial insects: the generalist field cricket, Gryllus texensis Cade and Otte (Orthoptera: Gryllidae) and a specialist curculionid weevil, Sabinia setosa (Le Conte) (Coleoptera: Curculionidae). Both species exhibited extensive intraspecific stoichiometric variation. Cricket body nitrogen content ranged from 8-12% and there was a four-fold difference in body phosphorus content, ranging from 0.32-1.27%. Body size explained half this stoichiometric variation, with larger individuals containing less nitrogen and phosphorus. Weevils exhibited an almost three-fold difference in body phosphorus content, ranging from 0.38-0.97%. Overall, the variation observed within each of these species is comparable to the variation previously observed across almost all terrestrial insect species. PMID- 20298115 TI - Genomic structure of the luciferase gene from the bioluminescent beetle, Nyctophila cf. caucasica. AB - The gene coding for beetle luciferase, the enzyme responsible for bioluminescence in over two thousand coleopteran species has, to date, only been characterized from one Palearctic species of Lampyridae. Here we report the characterization of the luciferase gene from a female beetle of an Iranian lampyrid species, Nyctophila cf. caucasica (Coleoptera:Lampyridae). The luciferase gene was composed of seven exons, coding for 547 amino acids, separated by six introns spanning 1976 bp of genomic DNA. The deduced amino acid sequences of the luciferase gene of N. caucasica showed 98.9% homology to that of the Palearctic species Lampyris noctiluca. Analysis of the 810 bp upstream region of the luciferase gene revealed three TATA boxes and several other consensus transcriptional factor recognition sequences presenting evidence for a putative core promoter region conserved in Lampyrinae from -190 through to -155 upstream of the luciferase start codon. Along with the core promoter region the luciferase gene was compared with orthologous sequences from other lampyrid species and found to have greatest identity to Lampyris turkistanicus and Lampyris noctiluca. The significant sequence identity to the former is discussed in relation to taxonomic issues of Iranian lampyrids. PMID- 20298116 TI - Repellent properties of delta-octalactone against the tsetse fly, Glossina morsitans morsitans. AB - Delta-octalactone, produced by several Bovidae, has been suggested as a potential repellant of tsetse fly attack. Racemic delta-octalactone was synthesized via an abbreviated route. The product was assayed against 3-day old starved teneral female tsetse flies, Glossina morsitans morsitans Wiedemann (Diptera: Glossinidae), in a choice wind tunnel and found to be a potent tsetse repellent at doses >or=0.05 mg in 200 microl of paraffin oil (0.05 >p >0.01). PMID- 20298117 TI - Interactions between population density of the Colorado potato beetle, Leptinotarsa decemlineata, and herbicide rate for suppression of solanaceous weeds. AB - The presence of volunteer potato Solanum tuberosum L., cutleaf nightshade, S. triflorum N., and hairy nightshade, S. physalifolium Rusby (Solanales: Solanaceae), throughout potato crop rotations can diminish the effectiveness of crop rotations designed to control disease and pest problems associated with growing potatoes. In greenhouse bioassays, larvae of the Colorado potato beetle, Leptinotarsa decemlineata Say (Coleoptera: Chrysomelidae) were placed in population densities of 0, 5, 10, and 40 per potato (cv. Russet Burbank) plant and 0, 5, 10, and 15 per cutleaf nightshade and hairy nightshade plant. Plants were treated with different rates of herbicides including fluroxypyr, prometryn, and mesotrione rates, and the physiological response on the potato plants was assessed by weighing shoot biomass 14 days after treatment. Consistently, across all bioassays, rate response functions were shifted as L. decemlineata density increased, such that less herbicide was required to achieve control. For instance, the herbicide rate needed to achieve 90% reduction in potato biomass was reduced from 62 to 0 g fluroxypyr per hectare and 711 to 0 g prometryn per hectare as L. decemlineata density was increased to 40 larvae per plant. Herbivory at higher L. decemlineata population densities and herbicides above certain rates resulted in large reductions in cutleaf and hairy nightshade biomass. Differences in rate response functions among L. decemlineata population densities indicated that L. decemlineata contributed to weed suppression in combination with herbicides. These data suggest that integrated weed management systems targeting volunteer potato, cutleaf nightshade, and hairy nightshade can be more effective when herbicide applications are combined with herbivory by naturally occurring Colorado potato beetles. PMID- 20298118 TI - Morphology and histology of the ductus receptaculi and accessory glands in the reproductive tract of the female cricket, Teleogryllus commodus. AB - The morphology and histology of the ductus receptaculi and accessory glands in females of the black field cricket, Teleogryllus commodus Walker (Orthoptera: Gryllidae) are described. Both are reproductive organs situated in the 7(th) and 8(th) abdominal segment that join the posterior part of the genital chamber. The ductus receptaculi is a long (up to 25 mm) homogeneous tube, and the accessory glands (total length: 4 to 12 mm) are a complex system of tubes and end lobes with various numbers of ramifications. Based on their external shapes the accessory glands may be subdivided into three distinct regions, a distal region mainly producing the gland's secretion, a middle conducting region, and a basal region serving for the storage and release of the secretory substances into the genital chamber of the female. In histological respects, both organs have an outer muscle coat followed by a basal lamina, one or two cell layers, the cuticular intima, and the inner lumen. The ductus receptaculi is subdivided into three histologically different regions. The region located adjacent to the receptaculum and the region neighbouring the terminal papilla consist of a single, epithelial cell layer that is not secretory. The epithelium of the middle region contains two cell layers, glandular cells and cuticula-forming cells, which are responsible for the production of the cuticular intima. The secretion of the gland cells is released into an extracellular cavity, through which it reaches the lumen via a complex network of canals running through the intima. The histology of the accessory glands is rather homogeneous among the different regions, as one layer of epithelial cells produces both the secretion and the cuticular intima. Histological variations in the distal, middle, and basal gland sections mainly concern the height of the epithelium, the thickness of the basal lamina and the cuticular intima as well as the variable presence of the outer muscle coat. In contrast to the ductus receptaculi, secretory substances produced by the accessory gland cells accumulate in the lumen by a diffusive permeation of the intima. PMID- 20298119 TI - Influence of host gender on infection rate, density and distribution of the parasitic fungus, Hesperomyces virescens, on the multicolored Asian lady beetle, Harmonia axyridis. AB - Hesperomyces virescens Thaxter (Laboulbeniales: Laboulbeniaceae) is a parasitic fungus that infects lady beetles (Coleoptera: Coccinellidae) via horizontal transmission between adults at overwintering and feeding sites. The differential behavior of male and female hosts could have profound effects on intensity of infection and positioning of fungus on the host's integument. The influence of host gender on infection rate, density and distribution of this parasite on the multicolored Asian lady beetle, Harmonia axyridis (Pallas) (Coleoptera: Coccinellidae), was determined at a feeding site. Adult H. axyridis were sampled from pecan, Carya illinoinensis (Wangenh.) K. Koch, trees in northern Mississippi, USA, during summer and early fall 2003-2004. Results indicated that the behavior of male or female beetles on pecan trees had only a limited effect on the intensity of infection. When averaged over the entire season, the percentage of H. axyridis infected with H. virescens was not influenced by host gender. In 2003, a seasonal average of 54 and 39% of males and females, respectively, were infected; whereas in 2004, 36 and 41% of male and female beetles, respectively, were infected. The percentage of males infected with H. virescens was correlated with the number of males captured at the site in 2003; infection rate decreased as male abundance increased. Infection rate did not correlate with female abundance in 2003 or male or female abundance in 2004. Host gender had a considerable effect on the density and distribution of the fungus. Hesperomyces virescens mature thalli were denser on male rather than female beetles. Also, thallus density was often greatest on the elytra, meso- and metathorax, and abdomen of males and elytra of females, than on other body parts, in 2003. In 2003 and 2004, approximately 59 and 97% and 67 and 96% of males and females, respectively, had mature thalli distributed on the elytra. Prevalence of H. virescens thalli on the dorsum of H. axyridis females suggests that mating behavior is important in fungal transmission. However, prevalence of thalli on the dorsum of H. axyridis males suggests that behaviors other than mating contribute to the transmission of H. virescens onto male beetles. Spread of H. virescens ascospores from infected to uninfected H. axyridis adults of different generations, at feeding sites, might be vital to maintaining stable populations of the fungus. PMID- 20298120 TI - Biomarkers of oxidative stress in overweight men are not influenced by a combination of antioxidants. AB - The effect of antioxidant supplementation on biomarkers of oxidative stress was investigated in a 6-week intervention study in 60 overweight men. The supplement contained a combination of antioxidants aiming to correspond to the antioxidant content found in a diet rich in fruit and vegetables. Placebo, single or double dose of antioxidants was provided to the subjects. Metabolic variables, plasma antioxidants and biomarkers of oxidative stress (lipid peroxidation and DNA damage) were measured. No effect of supplementation on biomarkers of oxidative stress was observed. Both intervention groups showed substantial increases of plasma antioxidants. This study demonstrated that supplementation with a combination of antioxidants did not affect lipid peroxidation and DNA damage in overweight men, despite increased concentrations of plasma antioxidants. The absence of antioxidant supplement effect might possibly be explained by the chosen study group having a normal level of oxidative stress, duration of the intervention and/or doses of antioxidants. PMID- 20298121 TI - The manganese superoxide dismutase mimetic, M40403, protects adult mice from lethal total body irradiation. AB - Over-expression of manganese superoxide dismutase (MnSOD) protects tissues from radiation. M40403 is a stable non-peptidyl mimetic of MnSOD that crosses cell membranes and is effective in reducing experimental inflammation. Male BALB/c mice were injected intraperitoneally (i.p.) and subcutaneously (s.c.) with M40403, 30 min before 6.5, 7.5 and 8.5 Gy total body irradiation (TBI). Whereas all control injected mice died after receiving 8.5 Gy TBI by day 17, 30 day survival of mice pre-treated i.p. with 40, 30, 20 or 10 mg/kg was 100%, 90%, 81% and 25%, respectively. The Dose Reduction Factor 50/30 for animals treated with 30 mg M40403 s.c. 30 min prior to TBI was 1.41. Decreased apoptosis of the large and particularly the small bowel and marked recovery of both lymphoid and hematopoietic tissues occurred in the M40403 pre-treated animals. M40403 is effective in reducing TBI-induced tissue destruction and has potential as a new radioprotective agent. PMID- 20298122 TI - Oxidative stress in the denervated muscle. AB - Following experimental hind limb denervation in rats, this study demonstrates that oxidative stress occurs and advances an hypothesis about its origin. In fact: (i) ROS are formed; (ii) membrane lipids are oxidized; (iii) oxidized ion channels and pumps may lead to increased [Ca(2+)](i); all the above mentioned events increase with denervation time. In the denervated muscle, (iv) mRNA abundance of cytoprotective and anti-oxidant proteins (Hsp70, Hsp27, Sod1, Catalase, Gpx1, Gpx4, Gstm1), as well as (v) SOD1 enzymatic activity and HSP70i protein increase; (vi) an unbalance in mitochondrial OXPHOS enzymes occurs, presumably leading to excess mitochondrial ROS production; (vii) increased cPLA2alpha expression (mRNA) and activation (increased [Ca(2+)](i)) may lead to increased hydroperoxides release. Since anti-oxidant defences appear inadequate to counterbalance increased ROS production with increased denervation time, an anti-oxidant therapeutic strategy seems to be advisable in the many medical conditions where the nerve-muscle connection is impaired. PMID- 20298124 TI - Type I interferons in systemic autoimmunity. AB - Type I IFN (IFN-I) was firstly described in 1957 as a soluble factor responsible for viral resistance in vitro. Today, it is well known that the IFN-I family comprises a wide number of cytokines with different modulatory effects on angiogenesis, cell growth, fibrosis, and apoptosis. However, one of the most important functions of IFN-I is the capability to trigger a complex array of cellular responses that result in a host-protective antiviral response. For this reason, IFN-I can be considered a "director" of protective immune responses. The recent finding of the so-called interferon signature in patients suffering from different autoimmune diseases has underlined its possible role in the pathogenesis of these diseases. On the other hand, IFN-alpha/beta is reported to be efficacious in the treatment of some autoimmune and infectious diseases not responsive to conventional therapy. On these occasions, the treated patients often start or increase autoantibody production supporting the role of IFN as inducer of an autoimmune response. In this review, we will underline recent acquisitions about IFN-I biology, with a focus on the relevance of the induction of some autoimmune diseases, such as systemic lupus erythematosus, systemic sclerosis, rheumatoid arthritis, dermato/polymiositis, and Sjogren's syndrome. PMID- 20298123 TI - Discrete changes in circulating regulatory T cells during infliximab treatment of Crohn's disease. AB - Deficiency of CD4+CD25+ regulatory T cells (Tregs) may be involved in Crohn's disease (CD) pathogenesis. In rheumatoid arthritis (RA), the anti-TNF-alpha antibody infliximab increases circulating Treg numbers. We aimed to evaluate circulating Tregs in CD before and after infliximab therapy. In 20 patients with active CD, blood samples were obtained before infusion of infliximab 5 mg/kg and 1, 7, and 42 days after therapy. Clinical, biochemical, and fecal markers of inflammation were obtained. Nine healthy volunteers served as controls. We applied a novel Treg marker, the absence of CD127 expression, to identify Tregs by whole-blood flow cytometry. Treg percentages were similar among CD patients [median 7.7%, interquartile range (IQR) 5.3-10.1%] and healthy volunteers (median 7.6% IQR 6.3-8.9%) with discrete changes (median 7.3%, IQR 4.5-10.1%) throughout the study period, irrespective of the significant clinical effect of infliximab. Unlike in RA, we found no arising population of CD62L - Tregs; however, we observed a rapid recruitment of lymphocytes and upregulation of the intestinal homing marker alpha4beta7 integrin on CD4+T cells. In conclusion, our results do not support the hypothesis that the clinical effect of infliximab is mediated by a reinforcement of defective, circulating Tregs in CD. PMID- 20298125 TI - Type I interferon therapy and its role in autoimmunity. AB - Interferons (IFNs) display a pleiotropic effect on different cell types of both the innate and the adaptive immunities being able to affect the immune responses. The ability of IFNs, and in particular of type I IFN, to activate dendritic cells and to modulate the expression of major histocompatibility classes I and II molecules supports their potential role also in the development and maintenance of tolerance. When tolerance breakdown has occurred, immunocomplexes generated by the reaction of nuclear antigens and specific autoantibodies can further induce type I IFN production. Accordingly, high acid-labile type I IFN plasma levels, overexpression of IFNalpha-induced transcripts and the association with genes closely related to type I IFN response represent the rationale for the so-called IFN signature in systemic lupus erythematosus, a prototypical autoimmune disease. The role of IFNs in autoimmunity is further supported by their direct and deleterious impact on target tissues. The therapeutic use of IFNs is based on their antiviral and antiproliferative effect. Type I IFN administration, in particular, is associated with the appearance of autoimmunity, although less frequently than expected. Such an event takes place mostly in patients with previous autoimmune manifestations and can be characterized by the appearance of autoantibodies only or of a clinically overt disease. IFN therapy cessation is usually, but not always, required for controlling the autoimmune disorders. PMID- 20298126 TI - Development of novel therapies for MG: Studies in animal models. AB - Experimental myasthenia gravis (MG) in animals, and in particular experimental autoimmune MG in rodents, serves as excellent models to study possible novel therapeutic modalities for MG. The current treatments for MG are based on cholinesterase inhibitors, general immunosuppressants, and corticosteroids, broad immunomodulatory therapies such as plasma exchange or intravenous immunoglobulins (IVIGs), and thymectomy for selected patients. This stresses the need for immunotherapies that would specifically or preferentially suppress the undesirable autoimmune response without widely affecting the entire immune system as most available treatments do. The available animal models for MG enable to perform preclinical studies in which novel therapeutic approaches can be tested. In this review, we describe the different therapeutic approaches that were so far tested in experimental models of MG and discuss their underlying mechanisms of action. These include antigen - acetylcholine receptor (AChR)-dependent treatments aimed at specifically abrogating the humoral and cellular anti-AChR responses as well as immunomodulatory approaches that could be used either alone or in conjunction with antigen-specific treatments or alternatively serve as steroid sparing agents. The antigen-specific treatments are based on fragments or peptides derived from the acetylcholine receptor (AChR) that would theoretically deviate the anti-AChR autoimmune response away from the muscle target or on ways to target AChR-specific T- and B- cell responses or antibodies. The immunomodulatory modalities include cell-based and non-cell-based ways to affect or manipulate key players in the autoimmune process such as regulatory T cells, dendritic cells, cytokine networks, and chemokine and costimulatory signaling as well as complement pathways. We also describe approaches that attempt to affect the cholinergic balance, which is impaired at the neuromuscular junction. In addition to enabling to test the feasibility of novel approaches, experimental MG enables to perform analyses of existing treatment modalities, which cannot be performed in human MG patients. These include studies on the mode of action of various immunosuppressants and on IVIGs. Hopefully, the vast repertoire of therapeutic approaches that are studied in experimental models of MG will pave the way to clinical studies that will eventually improve the management of MG. PMID- 20298128 TI - A practical and feasible control system for bifunctional myoelectric hand prostheses. AB - This paper presents an implementation of a practical and low-cost hardware-based control system for multifunctional myoelectric hand prostheses. The model utilizes a mode-switching technique in order to voluntarily control the operation of a dual-mode prosthetic device in two degrees of freedom: grasp/release and pronation/supination. This system was designed specifically to cater to the increasing needs of patients in developing countries, where myoelectric prostheses are scarce and extremely expensive. The design relied entirely on locally-available commercial components and aimed at allowing small prosthetics producers the freedom to utilize and modify the design according to their clients' preferences and requirements. Evaluation tests revealed excellent control and ability to execute basic hand and wrist functions even with short training periods, although results varied with the underlying level of muscular activity. PMID- 20298127 TI - ZnT8 autoantibody titers in type 1 diabetes patients decline rapidly after clinical onset. AB - Autoantibodies to the islet-specific zinc transporter isoform 8 (ZnT8) are detected in the majority of type 1 diabetes patients prior to and at clinical diagnosis. The presence of ZnT8Ab after diagnosis has not been investigated. This study analyzed the autoantibody response to ZnT8 in regard to age at onset and disease duration. Two new onset type 1 diabetes patient cohorts with different age distributions at onset (2-17 and 15-34 years of age at onset), a longitudinal subset of the younger type 1 diabetes patient cohort (n = 32), and a cohort of GAD65Ab-positive LADA patients (n = 47) was analyzed for the presence of autoantibodies directed to the two major isoforms, ZnT8-Arginine (ZnT8R) and ZnT8 Tryptophan (ZnT8W). The majority of type 1 diabetes patients tested positive for ZnT8Ab to both isoforms. ZnT8Ab titers were significantly higher in the younger type 1 diabetes patients as compared with the older cohort (ZnT8RAb at a median of 148 and 29 U/ml, respectively, p < 0.001) (ZnT8WAb at a median of 145 and 58 U/ml, respectively, p < 0.01). ZnT8RAb and ZnT8WAb titers were significantly lower in the LADA patients (ZnT8RAb at a median of 14 U/ml, ZnT8WAb at a median of 25 U/ml) as compared with either type 1 diabetes cohorts. In our longitudinal analysis of type 1 diabetes patients after clinical diagnosis, ZnT8Ab levels to both isoforms declined significantly during the initial year of disease (ZnT8RAb from a median of 320-162 U/ml, p = 0.0001; ZnT8WAb from a median of 128-46 U/ml, p = 0.0011). The antibody titers further declined during the following 4 years (p < 0.0001). We conclude that ZnT8Ab presents a useful marker for type 1 diabetes, especially in younger patients at disease diagnosis. PMID- 20298129 TI - Age at first prosthetic fitting and later functional outcome in children and young adults with unilateral congenital below-elbow deficiency: a cross-sectional study. AB - The objective of this study was to evaluate whether prosthetic fitting before the age of one year is associated with better outcomes in children with unilateral congenital below-elbow deficiency compared to children fitted after the age of one. Twenty subjects aged 6-21 years were recruited (five prosthetic users and 15 non-users). The Child Amputee Prosthetics Project-Prosthesis Satisfactory Inventory (CAPP-PSI) and the Prosthetic Upper Extremity Functional Index (PUFI) were used to assess patient satisfaction and functional use of the prosthesis. Videotapes were used to assess motor performance. Initial prosthetic fitting before one year of age was related to use of a prosthesis for at least four years. Age at first fitting was not associated with satisfaction with the prosthesis, functional use of the prosthesis or motor skills. Discrepancies between ease of performance with prosthesis and usefulness of the prosthesis as well as between capacity and performance of activities were found. The video assessments showed impaired movement adaptation to some tasks in six subjects. In conclusion, early prosthetic fitting seems to have a limited impact on prosthesis use during later stages of life. PMID- 20298130 TI - Maternal laboratory stress influences fetal neurobehavior: cortisol does not provide all answers. AB - OBJECTIVE: Maternal stress can have an impact on pregnancy. However, effects on fetal neurobehavior are not well understood. In this study, the effect of laboratory stress on maternal psychoneuroendocrinological response and on fetal neurobehavior was studied. Serum cortisol as a potential underlying mechanism was measured. METHODS: Twenty-seven women made a single 1.5-h visit in their third trimester. The laboratory stressor involved an arithmetic task. Associations between maternal laboratory stress response and fetal neurobehavior were analyzed by studying 19 maternal-fetal dyads with high signal quality cardiotocograms. RESULTS: Stress exposure changed participants stress perception (p < 0.0001). However, only half of the participants (responders) had an HPA-axis response. Fetuses responded to the stress exposure depending on their mothers' stress response: (i) there was a fetal heart rate (FHR) group effect at the level of trend (p = 0.06). Fetuses of responders had higher HR levels 20 min after the exposure (p = 0.043), (ii) there were interaction (p = 0.026) and group effects at the level of trend (p = 0.078) found for FHR short-term variation (STV). Fetuses of responders had lower FHR STV 20 min after stress exposure (p = 0.007). Cortisol as a potential underlying mechanism only seemed to be associated with short- and long-term variation of FHR. CONCLUSIONS: An activation of the maternal stress-system could result in a child being born having a history of responding to maternal stress. PMID- 20298131 TI - Valproate semisodium ER for migraine and cluster headache prophylaxis. AB - IMPORTANCE OF THE FIELD: Migraine and cluster headache (CH) are disabling syndromes that often require prophylactic treatment. Valproate semisodium ER (VPS ER) is FDA-approved for the treatment of epilepsy, acute mania in bipolar disorder and migraine prophylaxis. AREAS COVERED IN THIS REVIEW: We reviewed literature regarding VPS ER pharmacokinetics and its use in migraine and CH prophylaxis. WHAT THE READER WILL GAIN: VPS ER is well studied and effective in the preventive treatment of migraine and CH. This article reviews the evidence for its use, describes how to administer and dose this medication, and reviews important safety precautions. TAKE HOME MESSAGE: VPS ER is effective in the prophylactic treatment of migraine and CH. This once-a-day dosing formulation may increase compliance. PMID- 20298132 TI - Molecular biology and genetics in clinical chemistry and laboratory medicine. PMID- 20298133 TI - A methodological reappraisal of total and high molecular weight adiponectin determination in human peripheral circulation: comparison of four immunometric assays. AB - BACKGROUND: Adiponectin, present in different multimeric forms in circulation, is increasingly used in clinical settings as a cardiometabolic marker. The development of several commercially available enzyme-linked immunosorbent assays (ELISA) has allowed for the widespread measurement of adiponectin in research as well as in clinical practice. The comparative performance of these assays is thus an issue of major relevance. METHODS: The analytical performance of four different ELISAs (LINCO, B-Bridge, SPIbio and ALPCO) was evaluated. Samples from 102 cardiac patients and 40 healthy subjects were tested using LINCO and ALPCO. The latter is able to measure the concentrations of multimers. For the multimer assay, an error propagation study was performed. A subset of subjects was tested by all four ELISAs for comparison purposes. RESULTS: Bland-Altman plots revealed differences between the results of the four ELISAs, mainly for ALPCO. However, a strong correlation between the different ELISAs (ALPCO, r=0.83; B-Bridge, r=0.98; SPIbio, r=0.91 vs. LINCO) was observed. Total adiponectin measured by LINCO showed a better association with cardiac disease [receiver-operating characteristic (ROC) curves] than total and high molecular weight adiponectin measured by ALPCO. CONCLUSIONS: The results of this study contribute to a better understanding of the methodological features of the several ELISAs, and help in the evaluation and comparison of the relative results. PMID- 20298134 TI - Interpretation of serum parathyroid hormone concentrations in dialysis patients: what do the KDIGO guidelines change for the clinical laboratory? AB - The Kidney Disease: Improving Global Outcomes (KDIGO) have recently replaced the K/DOQI guidelines to help nephrologists in diagnosing, treating and monitoring chronic kidney disease mineral and bone disorders (CKD-MBD). Here, we comment on the KDIGO recommendations concerning the interpretation of parathyroid hormone (PTH) concentrations in dialysis patients: "In patients with CKD stage 5D, we suggest maintaining iPTH in the range of approximately two to nine times the upper normal limit of the assay. We suggest that marked changes in PTH concentrations in either direction within this range prompt an initiation or change in therapy to avoid progression to concentrations outside of this range". Our comments concern the interpretation of PTH in dialysis patients, but also the more global problem of establishing normal values for PTH. PMID- 20298135 TI - IFCC reference procedures for measurement of the catalytic concentrations of enzymes: corrigendum, notes and useful advice. International Federation of Clinical Chemistry and Laboratory Medicine (IFCC)--IFCC Scientific Division. AB - The primary reference measurement procedures (PRMPs) for the international standardization of catalytic concentration measurements of alpha-amylase, alanine aminotransferase, aspartate aminotransferase (AST), creatine kinase (CK), gamma glutamyltransferase and lactate dehydrogenase have been performed in reference laboratories for several years. The IFCC Committee on Reference Systems for Enzymes and two reference laboratories, with official accreditation for the PRMPs, have collected useful information on some of the steps of the reference procedures that require special attention. This document comprises errata corrige for minor mistakes in published PRMPs for AST and CK. Several notes on the PRMPs are emphasized. This includes details that are very important for improved standardization, and general suggestions for reducing measurement uncertainty. PMID- 20298136 TI - Microsatellite polymorphisms in intron 2 of the toll-like receptor 2 gene and their association with susceptibility to pulmonary tuberculosis in Han Chinese. AB - BACKGROUND: Toll-like receptor 2 (TLR2) is essential for the immune response to tuberculosis (TB). The goal of the present study was to investigate whether the guanine-thymine (GT) repeat microsatellite polymorphism in intron 2 of the TLR2 gene might be correlated with susceptibility to TB in Han Chinese. METHODS: The number of (GT)n repeats was determined by gene scanning from 244 patients with TB and 233 control subjects. The expression of TLR2 on CD14+ peripheral blood mononuclear cells was determined using flow cytometry. RESULTS: No association in allelic polymorphism between control subjects and patients with TB was found. However, the S/M genotype of the microsatellite polymorphism was more frequent in TB patients than in healthy controls (p=0.01). The S/L genotype was more popular in controls than in patients with TB (p=0.007). TLR2 expression was higher in subjects with the S/L genotype than in those with the S/M genotype (p<0.05). CONCLUSIONS: Our data suggest that the S/M genotype of the microsatellite (GT)n polymorphisms in intron 2 of the TLR2 gene may increase susceptibility to TB in Chinese, and the S/L genotype may act as a negative risk factor. PMID- 20298137 TI - New quantitative electrochemiluminescence method (ECLIA) for interleukin-6 (IL-6) measurement. AB - BACKGROUND: A new interleukin-6 (IL-6) electrochemiluminescent immunoassay (ECLIA, Roche Diagnostics) was evaluated and compared to a previous semiquantitative immunoassay (Milenia Biotec). Reference ranges for cord blood plasma were also calculated. METHODS: The new IL-6 ECLIA test was performed using a Cobas E601 analyzer (Roche Diagnostics). The comparison method (Milenia Biotec) was a semiquantitative lateral flow immunoassay, coupled to a digital image capture system (PicoScan). Healthy at term newborns were recruited to establish reference ranges for IL-6 in cord blood plasma. RESULTS: Total imprecision ranged from 3.7% to 8.0% depending on the IL-6 concentrations. The calculated limit of detection for IL-6 measured by ECLIA was 2.63 pg/mL, almost twice as high as that claimed by the manufacturer (1.5 pg/mL). The linearity of the method was verified to 5000 pg/mL. The IL-6 reference limit, obtained from 148 cord blood samples, was 30 pg/mL (90% confidence interval: 19-48 pg/mL). CONCLUSIONS: The new quantitative ECLIA method showed good reproducibility, linearity and functional sensitivity. Additional clinically based studies are needed to elucidate the usefulness of the IL-6 reference limit, calculated here for the first time by ECLIA in cord blood plasma, to aid in the diagnosis of vertical transmission of sepsis. PMID- 20298138 TI - Diagnostic performance of anti-citrullinated peptide antibodies for the diagnosis of rheumatoid arthritis: the relevance of likelihood ratios. AB - BACKGROUND: The goal of our study was to evaluate the diagnostic performance of the anti-cyclic citrullinated peptide 2 (anti-CCP2) assay in patients with autoimmune and inflammatory disorders. METHODS: We tested the specificity and sensitivity of anti-CCP2 antibodies measured by ELISA in 787 patients with rheumatoid arthritis (RA), 1024 patients with other autoimmune/inflammatory rheumatic disease and 401 subjects without autoimmune rheumatic disease. The optimal cut-off value was defined as the value with the highest diagnostic accuracy (receiver operating characteristic curve analysis). Interval-specific likelihood ratios (LRs) were calculated for each range bounded by defined anti CCP2 values. RESULTS: To distinguish between patients with RA and controls, the cut-off value with the highest diagnostic accuracy for anti-CCP2 was 2.8 U/mL. Comparing the optimal cut-off value for anti-CCP2 to that recommended by the manufacturer (5.0 U/mL), an increase in prevalence between the proportions of test-positive patients was found for RA, undifferentiated connective tissue disease and undifferentiated arthritis. Evaluating interval-specific LRs for the selected ranges bound by two anti-CCP2 values, in RA and diseased controls, the LRs were 0.40 for values <5.0 U/mL, 6.66 for 5.0-15.0 U/mL, 27.01 for 15.1-30.0 U/mL and 28.89 for >30.0 U/mL. CONCLUSIONS: The cut-off value of 2.8 U/mL for anti-CCP2 has the highest diagnostic accuracy. A value of anti-CCP2 >15 U/mL is associated with an increase in the likelihood of RA disease. PMID- 20298139 TI - Rhabdomyolysis: historical background, clinical, diagnostic and therapeutic features. AB - Rhabdomyolysis, a term used to describe the rapid breakdown of striated muscle, is characterized by rupture and necrosis of muscle fibers. This process results in the release of cell breakdown products into the bloodstream and extracellular space. Although direct muscle injury remains the most common cause of muscle injury, additional causes include hereditary enzyme disorders, drugs, toxins, endocrinopathies, malignant hyperthermia, neuroleptic malignant syndrome, heatstroke, hypothermia, electrolyte alterations, diabetic ketoacidosis and non ketotic hyperosmolar coma, severe hypo- or hyperthyroidism and bacterial or viral infections. The classic triad of symptoms includes muscle pain, weakness and dark urine, although more than 50% of the patients do not complain of muscle pain or weakness. Additional systemic symptoms include fever, general malaise, tachycardia, nausea and vomiting. The laboratory diagnosis is based essentially on the measurement of creatine kinase in serum or plasma. Plasma and urine myoglobin measurement might be useful in the early stages of the syndrome and for identifying a subset of patients with minor skeletal muscle injury. Patient monitoring is pivotal (the mortality rate is as high as 8%), and should be focused on preventing the detrimental consequences, that often include renal disease and coagulopathy. In the pre-hospital setting, forced hydration with 1.5 2 L of sterile saline solution should be started immediately, followed by 1.5-2 L/h. Following hospital admission, continuous hydration should be ensured, alternating the saline solution with a 5% glucose solution. In the presence of myoglobinuria, urine should be alkalinized by use of sodium bicarbonate solution. Clin Chem Lab Med 2010;48:749-56. PMID- 20298140 TI - Performance characteristics of a microfluidic Lab-on-Chip electrophoresis system for high-density lipoprotein (HDL) subfraction separation and measurement. AB - BACKGROUND: High-density lipoprotein (HDL) is believed to be protective against coronary heart disease (CHD). HDL is comprised of different subfractions. Of these, HDL 2b is believed to be the most important in preventing CHD. Current methods for HDL subfraction measurements are not standardized and often exhibit poor analytical performance, which can limit their usefulness in clinical practice. METHODS: We have developed a microfluidic Lab-on-Chip electrophoresis system for serum HDL subfraction measurements. Linear polymers are used as a sieving buffer for HDL particle separation. Nine samples and two controls can be analyzed in 30 min. The percent HDL 2b that comprises total high-density lipoprotein cholesterol (HDL-C) is reported. RESULTS: Samples with HDL-C of 0.259 2.072 mmol/L could be evaluated for percent HDL 2b with coefficient of variations (%CVs) below 8%. Total precision was typically below 1.5% and linearity was observed between 8% and 32% HDL 2b. Measurements were not affected by many therapeutic and biological compounds. Consistent results were obtained by three laboratories and showed r(2) values between 0.93 and 0.95. CONCLUSIONS: The assay allows for easy and reproducible measurement of percent HDL 2b. The experimental procedure and small size of the instrumentation needed for measurement make it viable in clinical settings. PMID- 20298142 TI - Unilateral hand-foot syndrome: an extraordinary side effect of capecitabine. AB - BACKGROUND: Hand-foot syndrome (HFS), the most common toxicity of capecitabine, is characterized by tingling, numbness, pain, erythema, dryness, rash, swelling, increased pigmentation, and/or pruritus of the palmar and/or plantar surfaces of the hands and/or feet. HFS is usually seen in both the hands and the feet, with varying severity. We have previously published a case report of dihydropyrimidine dehydrogenase (DPD) deficiency that manifested a variant of HFS. CASE REPORT: We report the case of a 65-year-old Turkish Cypriot male patient with advanced gastric cancer who developed pain, numbness, and reddening in his left palm and left sole 10 days after the fourth cycle of capecitabine at a dose of 1,000 mg/m(2)/day twice daily (BID) on days 1 to 14 every 21 days. On physical examination, he had unilaterally erythematous changes and skin scaling on his left sole and palm consistent with grade II HFS. After stopping administration of capecitabine and supportive management, the HFS resolved in a week's time. CONCLUSIONS: To the best of our knowledge, this is the first case of capecitabine induced unilateral HFS. Further investigation related to this toxicity associated with capecitabine is warranted. PMID- 20298143 TI - Spontaneous formation of multinucleated giant cells with bone resorbing activity by long culture of human peripheral blood CD14-positive monocytes in vitro. AB - Several reports indicate that multinucleated giant cells that derived from human peripheral blood CD14-positive monocytes have osteoclastic properties, and although the mechanism is not completely understood, the authors have previously demonstrated that spontaneous osteoclastogenesis from monocytes can occur. Here, the authors investigated the effect of detachment and long-term cultures in this process. When monocytes were incubated for 2 weeks, spontaneous formation of polykaryocytes was rarely observed. In addition, when monocytes precultured for 2 weeks were detached by a cell scraper and further subcultured, almost all cells died. Surprisingly, when monocytes were incubated for 8 weeks without any pro osteoclastogenic factors and without detachment, the authors observed the spontaneous formation of tartrate-resistant acid phosphatase (TRAP)-positive polykaryocytes that were able of lacunae resorption. These findings indicate that cell adhesion is a prerequisite for differentiation and survival of CD14-positive monocytes, and that a long incubation period spontaneously induces multinucleation and bone-resorbing activity of monocytes, even in the absence of osteoclastogenesis-stimulating factors. PMID- 20298145 TI - Immunopharmacological role of the leukotriene receptor antagonists and inhibitors of leukotrienes generating enzymes in multiple sclerosis. AB - BACKGROUND AND AIM: Multiple sclerosis (MS) is a chronic inflammatory disease that involves central nervous system, and is generally associated with demyelination and axonal lesion. The effective factors for initiation of the inflammatory responses have not been known precisely so far. Leukotrienes (LTs) are inflammatory mediators with increased levels in the cerebrospinal fluid of MS patients and in experimental models of multiple sclerosis. Inhibition of LT receptors with specific antagonists can decrease inflammatory responses. In this review article we try to clarify the role of LT receptor antagonists and also inhibitors of enzymes which are involved in LTs generating pathway for treating multiple sclerosis as new targets for MS therapy. Moreover, we suggest that blockage of LT receptors by potent specific antagonists and/or agonists can be as a novel useful method in treatment of MS. PMID- 20298144 TI - Low connexin channel-dependent intercellular communication in human adult hematopoietic progenitor/stem cells: probing mechanisms of autologous stem cell therapy. AB - Human bone marrow is a clinical source of autologous progenitor stem cells showing promise for cardiac repair following ischemic insult. Functional improvements following delivery of adult bone marrow CD34(+) cells into heart tissue may require metabolic/electrical communication between participating cells. Since connexin43 (Cx43) channels are implicated in cardiogenesis and provide intercellular connectivity in the heart, the authors analyzed the expression of 20 connexins (Cx) in CD34(+) cells and in monocytes and granulocytes in bone marrow and spinal cord. Reverse transcriptase-polymerase chain reaction (RT-PCR) detected only low expression of Cx43 and Cx37. Very low level dye coupling was detected by flow cytometry between CD34(+) cells and other Cx43 expressing cells, including HL-1 cardiac cells, and was not inhibited by specific gap junction inhibitors. The results indicate that CD34(+) cells are unlikely to communicate via gap junctions and the authors conclude that use of CD34(+) cells to repair damaged hearts is unlikely to involve gap junctions. The results concur with the hypothesis that bone marrow cells elicit improved cardiac function through release of undefined paracrine mediators. PMID- 20298146 TI - Novel microbial diversity retrieved by autonomous robotic exploration of the world's deepest vertical phreatic sinkhole. AB - The deep phreatic thermal explorer (DEPTHX) is an autonomous underwater vehicle designed to navigate an unexplored environment, generate high-resolution three dimensional (3-D) maps, collect biological samples based on an autonomous sampling decision, and return to its origin. In the spring of 2007, DEPTHX was deployed in Zacaton, a deep (approximately 318 m), limestone, phreatic sinkhole (cenote) in northeastern Mexico. As DEPTHX descended, it generated a 3-D map based on the processing of range data from 54 onboard sonars. The vehicle collected water column samples and wall biomat samples throughout the depth profile of the cenote. Post-expedition sample analysis via comparative analysis of 16S rRNA gene sequences revealed a wealth of microbial diversity. Traditional Sanger gene sequencing combined with a barcoded-amplicon pyrosequencing approach revealed novel, phylum-level lineages from the domains Bacteria and Archaea; in addition, several novel subphylum lineages were also identified. Overall, DEPTHX successfully navigated and mapped Zacaton, and collected biological samples based on an autonomous decision, which revealed novel microbial diversity in a previously unexplored environment. PMID- 20298147 TI - Performance of orbital neutron instruments for spatially resolved hydrogen measurements of airless planetary bodies. AB - Orbital neutron spectroscopy has become a standard technique for measuring planetary surface compositions from orbit. While this technique has led to important discoveries, such as the deposits of hydrogen at the Moon and Mars, a limitation is its poor spatial resolution. For omni-directional neutron sensors, spatial resolutions are 1-1.5 times the spacecraft's altitude above the planetary surface (or 40-600 km for typical orbital altitudes). Neutron sensors with enhanced spatial resolution have been proposed, and one with a collimated field of view is scheduled to fly on a mission to measure lunar polar hydrogen. No quantitative studies or analyses have been published that evaluate in detail the detection and sensitivity limits of spatially resolved neutron measurements. Here, we describe two complementary techniques for evaluating the hydrogen sensitivity of spatially resolved neutron sensors: an analytic, closed-form expression that has been validated with Lunar Prospector neutron data, and a three-dimensional modeling technique. The analytic technique, called the Spatially resolved Neutron Analytic Sensitivity Approximation (SNASA), provides a straightforward method to evaluate spatially resolved neutron data from existing instruments as well as to plan for future mission scenarios. We conclude that the existing detector--the Lunar Exploration Neutron Detector (LEND)--scheduled to launch on the Lunar Reconnaissance Orbiter will have hydrogen sensitivities that are over an order of magnitude poorer than previously estimated. We further conclude that a sensor with a geometric factor of approximately 100 cm(2) Sr (compared to the LEND geometric factor of approximately 10.9 cm(2) Sr) could make substantially improved measurements of the lunar polar hydrogen spatial distribution. PMID- 20298148 TI - The Mars Astrobiology Explorer-Cacher (MAX-C): a potential rover mission for 2018. Final report of the Mars Mid-Range Rover Science Analysis Group (MRR-SAG) October 14, 2009. AB - This report documents the work of the Mid-Range Rover Science Analysis Group (MRR SAG), which was assigned to formulate a concept for a potential rover mission that could be launched to Mars in 2018. Based on programmatic and engineering considerations as of April 2009, our deliberations assumed that the potential mission would use the Mars Science Laboratory (MSL) sky-crane landing system and include a single solar-powered rover. The mission would also have a targeting accuracy of approximately 7 km (semimajor axis landing ellipse), a mobility range of at least 10 km, and a lifetime on the martian surface of at least 1 Earth year. An additional key consideration, given recently declining budgets and cost growth issues with MSL, is that the proposed rover must have lower cost and cost risk than those of MSL--this is an essential consideration for the Mars Exploration Program Analysis Group (MEPAG). The MRR-SAG was asked to formulate a mission concept that would address two general objectives: (1) conduct high priority in situ science and (2) make concrete steps toward the potential return of samples to Earth. The proposed means of achieving these two goals while balancing the trade-offs between them are described here in detail. We propose the name Mars Astrobiology Explorer-Cacher(MAX-C) to reflect the dual purpose of this potential 2018 rover mission. PMID- 20298149 TI - Prognosis of isolated mild to moderate fetal cerebral ventriculomegaly: a systematic review. AB - AIMS: To ascertain risk of aneuploidy, infection and neurological abnormality for the fetus diagnosed with isolated mild (10.1-12.0 mm) to moderate (12.1-15.0 mm) cerebral ventriculomegaly and to compare the neurological outcome between symmetrical vs. asymmetrical and stable vs. progressive ventriculomegaly. METHODS: A systematic review was conducted. Literature was identified by searching two bibliographical databases between 1980 and 2009 without language restrictions. The data extracted were inspected for heterogeneity. Overall rates and confidence intervals (CIs) for each prognostic factor were calculated. When comparative data existed, the odds ratio (OR) was calculated. RESULTS: The search strategy yielded 2150 relevant citations of which 28 studies were included in the review. The overall rate of infection and chromosomal abnormality was 1.5 and 5% (95% CI 3, 7), respectively. The risk of neurological abnormality regardless of karyotype or infection screen was 14% (95% CI 10, 18) and this reduced to 12% (95% CI 9, 15) when both chromosomes and infection screen were normal. The risk of neurological abnormality was significantly lower in stable compared to progressive ventriculomegaly [OR 0.29 (95% CI 0.15, 0.58)]. No significant differences were detected when symmetrical vs. asymmetrical ventriculomegaly were compared [OR 0.91 (95% CI 0.34, 2.41)]. CONCLUSION: This systematic review provides the physician with some estimates of prognosis in cases of isolated mild to moderate ventriculomegaly. PMID- 20298151 TI - Carcinogenesis and therapeutic strategies in thyroid cancer. AB - Current therapeutic options for patients with progressive thyroid cancer are relatively ineffective. There is a clear need to develop new alternatives for the management of this malignancy. As the knowledge of thyroid cancer biology advances, a large number of genetic events, molecular abnormalities, alterations of signaling pathways have been identified in the development and progression of thyroid neoplasms, and the potential exists to develop compounds targeted to treat thyroid cancers that do not respond to traditional therapy. In this review we described the recent development in thyroid carcinogenesis where the potential and novel intervention may exist. The discussion of thyroid carcinogenesis was integrated with exploitation of anti-thyroid agents that are currently either in clinical trials or in preclinical development for thyroid cancer. PMID- 20298150 TI - Targeting apoptosis pathway with natural terpenoids: implications for treatment of breast and prostate cancer. AB - Terpenoids represent a large and diverse class of naturally occurring compounds found in a variety of fruits, vegetables and medicinal plants. Structurally some of the terpenoids are similar to human hormones. A diet rich in terpenoids is inversely related with the risk of chronic diseases including cancers. Breast and prostate cancers are hormone-related diseases and the second leading cause of female and male cancer mortality. Diterpenoid paclitaxel, and its semi-synthetic analogue docetaxel, have entered clinical use against established breast and prostate cancers. Here we reviewed potential molecular targets and biological properties of natural terpenoids, including monoterpenoids, diterpenoids, triterpenoids and tetraterpenoids, and their applications in treatment of human breast and prostate cancers. These terpenoids are able to inhibit tumor cell proliferation and induce tumor cell death by inhibiting multiple cancer-specific targets including the proteasome, NF-kappaB, and antiapoptotic protein Bcl-2. The efficacy of these terpenoids against breast or prostate cancer cells, as demonstrated in pre-clinical studies support clinical application of these naturally occurring terpenoids in treatment of hormone-related human cancers. PMID- 20298152 TI - Targeting cellular proapoptotic molecules for developing anticancer agents from marine sources. AB - Apoptosis as a form of programmed cell death is a critical defense mechanism against the formation and progression of cancer and exhibits distinct morphological and biochemical traits. In an in vivo situation, apoptosis functions to eliminate potentially deleterious cells without causing such adverse effects as inflammatory response and ensuing scar formation. Therefore, targeting apoptotic pathways becomes an intriguing strategy for the development of chemotherapeutic agents. Marine natural products have become an important source in the discovery of antitumor drugs, especially when modern technology makes it more and more feasible to collect organisms from seas. Although lack of an analog of a long ethno-medical history for finding clues, as compared with terrestrial habitats, still hinders the progress, an increasing number of compounds have been isolated from marine organisms that have been found to possess apoptosis-inducing and anticancer activities. This primer summarizes several such compounds, based on their effects on apoptotic signaling pathways, although most of these products have not yet been studied in depth for their mechanisms of action. PMID- 20298153 TI - Chemosensitization of prostate cancer by modulating Bcl-2 family proteins. AB - A major challenge in oncology is the development of chemoresistance. This often occurs as cancer progresses and malignant cells acquire mechanisms to resist insults that would normally induce apoptosis. The onset of androgen independence in advanced prostate cancer is a prime example of this phenomenon. Overexpression of the pro-survival/anti-apoptotic proteins Bcl-2, Bcl-xL, and Mcl-1 are hallmarks of this transition. Here we outline the evolution of therapeutics designed to either limit the source or disrupt the interactions of these pro survival proteins. By either lessening the stoichiometric abundance of Bcl 2/xL/Mcl-1 in reference to their pro-apoptotic foils or freeing these pro apoptotic proteins from their grip, these treatments aim to sensitize cells to chemotherapy by priming cells for death. DNA anti-sense and RNA interference have been effectively employed to decrease Bcl-2 family mRNA and protein levels in cell culture models of advanced prostate cancer. However, clinical studies are lagging due to in vivo delivery challenges. The burgeoning field of nanoparticle delivery holds great promise in helping to overcome the challenge of administering highly labile nucleic acid based therapeutics. On another front, small molecule inhibitors that block the hetero-dimerization of pro-survival with pro-apoptotic proteins have significant clinical advantages and have advanced farther in clinical trials with promising early results. Most recently, a peptide has been discovered that can convert Bcl-2 from a pro-survival to a pro-apoptotic protein. The future may lie in targeting multiple steps of the apoptotic pathway, including Bcl-2/xL/Mcl-1, to debilitate the survival capacity of cancer cells and make chemotherapy induced death their only option. PMID- 20298155 TI - Targeting the p53-family in cancer and chemosensitivity: triple threat. AB - The p53-family of transcription factors consists of three genes - p53, p63, and p73 - that share significant structural and functional similarities. Although these genes encode multiple variants that have opposing functions in cancer biology, the full-length, transactivating (TA) p53-family members are potent inducers of apoptosis and tumor suppression. Many anti-cancer agents, from traditional chemo- and radiation therapies to more recently developed small molecules, exert their effects by enhancing the anti-proliferative effects of p53 and TAp63/p73. In this review, we provide an overview of the regulatory pathways controlling the p53-family proteins as a framework for understanding p53-family targeted drug mechanisms. We will also summarize recent work on promising attempts to re-activate p53 in tumors. In addition, we will discuss how p63 and p73 - the two more recently discovered p53-family members - have affected drug discovery and how these two genes may also hold promise as drug targets for recent and future novel therapies. This review will emphasize how targeting multiple members of the family of p53 proteins is likely to provide an increased threat to the growth of cancer cells. PMID- 20298156 TI - Anticancer properties of indole compounds: mechanism of apoptosis induction and role in chemotherapy. AB - Indole compounds, obtained from cruciferous vegetables, have been investigated for their putative anti-cancer properties. Studies with indole-3-carbinol (I3C) and its dimeric product, 3, 3' diindolylmethane (DIM), have indicated efficacy of these compounds against a number of human cancers. Available as well as emerging data suggests that these compounds act on a number of cellular signaling pathways leading to their observed biological effects. Such pleiotropic effects of these compounds are also considered crucial for their chemosensitization activity wherein they help reduce the toxicity and resistance against conventional chemotherapeutic drugs. These observations have major clinical implications especially in chemotherapy. Through this review, we have attempted to update current understanding on the state of anti-cancer research involving indole compounds. We have also summarized the available literature on modulatory effects of indoles on molecular targets such as survivin, uPA/uPAR and signaling pathways such as the NF-kappaB pathway, which are important for the apoptosis-inducing and chemosensitizing properties of these compounds. PMID- 20298158 TI - Low grade inflammation as a common pathogenetic denominator in age-related diseases: novel drug targets for anti-ageing strategies and successful ageing achievement. Part I. PMID- 20298157 TI - Role of apoptosis in chemotherapy. PMID- 20298159 TI - Low grade inflammation as a common pathogenetic denominator in age-related diseases: novel drug targets for anti-ageing strategies and successful ageing achievement. Part II. PMID- 20298154 TI - EGFR(S) inhibitors in the treatment of gastro-intestinal cancers: what's new? AB - In the past 10 to 15 years, a considerable progress has been made in the treatment of gastrointestinal (GI) related malignancies, as number of agents expanded from only one in 1995 to seven in 2006. Current review describes the recent role of targeted therapies, specifically EGFR inhibitors in the treatment of GI cancers. Importance of dietary agents in the treatment and prevention of GI cancers is also reviewed. PMID- 20298161 TI - Liver cancer stem cells as an important target in liver cancer therapies. AB - Hepatic cancer is one of most common cause of cancer-related death. Hepato epithelial cancers are believed to originate from the malignant transformation of liver-resident stem/progenitor cells. Liver cancer stem cells have been characterized recently and the phenotype of liver cancer stem cells has been defined as CD133+ CD44+ cancer cells. Recently, it has been also demonstrated about the relevance of targeting liver cancer stem cells, due to cancer stem cells are related to cancer metastasis. These advances no doubt to bring the new strategy in liver cancer treatment and control in this disease. This review describes the current status and progress about cancer stem cell research in liver and discuss of the implications of these studies in new liver cancer treatment strategies. PMID- 20298162 TI - Editorial: Physical and chemical agents inducing cell death and differentiation. PMID- 20298163 TI - Molecularly targeted therapies in breast cancer bone metastases. PMID- 20298164 TI - Editorial--"Current aging science": an important platform for reporting advances in aging-related research. PMID- 20298165 TI - DNA repair in premature aging disorders and neurodegeneration. AB - The accumulation of DNA damage has been widely implicated in premature aging and neurodegeneration. Progeroid syndromes with defects in the cellular response to DNA damage suggest that progressive genome instability represents an important aspect of the aging process. Moreover, most of the major neurodegenerative diseases are characterized by the accumulation of neuronal DNA damage, suggesting that impaired DNA repair mechanisms might be relevant to both premature aging and neurodegeneration. Two progeroid syndromes, Hutchinson-Gilford progeria syndrome and Werner's syndrome, are characterized by clinical features mimicking physiological aging at an early age and molecular studies have implicated decreased cell proliferation and altered DNA-damage responses as common causal mechanisms in the pathogenesis of both diseases. Defects in nucleotide excision repair cause three distinct human diseases: xeroderma pigmentosum, Cockayne's syndrome and trichothiodystrophy; each of them is characterized by premature onset of pathologies that overlap with those associated with old age in humans. Increasing evidence also suggests that an impaired DNA repair, particularly the base excision repair pathway, might play a fundamental role in the development of age-related neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis and Huntington' s disease. Here, we review the current knowledge on the role of DNA repair in premature aging and neurodegenerative diseases. PMID- 20298166 TI - Effects of caloric restriction on age-related hearing loss in rodents and rhesus monkeys. AB - Age-related hearing loss (AHL), also known as presbycusis, is a universal feature of mammalian aging and is the most frequently occurring sensory disorder in the elderly population. AHL is characterized by a decline of auditory function and loss of hair cells and spiral ganglion neurons in the cochlea of the inner ear. It has been postulated that AHL occurs gradually as a result of the cumulative effect with aging of exposure to noise, diet, oxidative damage, and mitochondrial DNA mutations. However, the molecular mechanisms of AHL remain unclear and no preventative or therapeutic interventions have been developed. A growing body of evidence suggests increased oxidative damage with aging to macromolecules such as DNA, proteins, and lipids may play a causal role in aging and age-related diseases. Caloric restriction (CR) extends the lifespan of most mammalian species, delays the onset of multiple age-related diseases, and attenuates both the degree of oxidative damage and the associated decline in physiological function. Here, we review studies on CR's ability to prevent cochlear pathology and AHL in laboratory animals and discuss potential molecular mechanisms of CR's actions. PMID- 20298167 TI - The effects of rapid- or intermediate-acting insulin on the proliferation and differentiation of cultured chondrocytes. AB - In cartilage regenerative medicine, which is highly expected in the face of our aging society, insulin is the potent factor for culture media. To secure the safety of culture media, we attempted to use medical insulin formulations, and compared their effects on human articular or auricular chondrocytes between regular human insulin (R) and neutral protamine hagedorn insulin (N). In monolayer culture with the media containing either R or N, the cell growth reached approximately 15-fold-increase in 6 days, which showed no significant difference between them. These cells showed the equivalent ability to produce cartilage matrices, both in vitro and in vivo. Also, in the 3D culture of the dedifferentiated chondrocytes, either R or N increased gene expression of type II collagen at 3-4 folds in the combination with other growth factors, compared with basal medium, while insulin could similarly enhance both the redifferentiation and cartilage maturation. The in vitro half-life of each insulin in the presence of chondrocytes neither decreased within 3 days, suggesting little degradation in the culture media, unlike in the body. Although both R and N showed similar biological effects on cultured chondrocytes, we may choose the R for clinical practice because of its pure composition. PMID- 20298169 TI - Fishing for age-related visual system mutants: behavioral screening of retinal degeneration genes in zebrafish. AB - The zebrafish (Danio rerio) has recently become a mainstream model system for genetic studies of human diseases, such as neurological degenerative diseases, heart diseases, immuno-system disorders, etc. In this article, we will review some recent findings of the usefulness of zebrafish as a model vertebrate for behavioral screening of mutations in vertebrate visual system, for example, genes involved in age-related retinal degeneration. PMID- 20298168 TI - Polyphenols and aging. AB - Age-associated changes within an individual are inherently complex and occur at multiple levels of organismal function. The overall decline in function of various tissues is known to play a key role in both aging and the complex etiology of certain age-associated diseases such as Alzheimer's disease (AD) and cancer. Continuing research highlights the dynamic capacity of polyphenols to protect against age-associated disorders through a variety of important mechanisms. Numerous lines of evidence suggest that dietary polyphenols such as resveratrol, (-)-epigallocatechin-3-gallate (EGCG), and curcumin have the capacity to mitigate age-associated cellular damage induced via metabolic production of reactive oxygen species (ROS). However, recently acquired evidence also demonstrates a likely role for these polyphenols as anticancer agents capable of preventing formation of new vasculature in neoplastic tissues. Polyphenols have also been shown to possess other anticancer properties such as specific cell-signaling actions that may stimulate the activity of the regulatory protein SIRT1. Additionally, polyphenolic compounds have demonstrated their inhibitory effects against chronic vascular inflammation associated with atherosclerosis. These increasingly well-documented results have begun to provide a basis for considering the use of polyphenols in the development of novel therapies for certain human diseases. And while the mechanisms by which these effects occur are yet to be fully understood, it is evident that further investigation may yield a potential use for polyphenols as pharmacological interventions against specific age-associated diseases. PMID- 20298170 TI - Treatment of Alzheimer's disease: symptomatic and disease-modifying approaches. AB - The two major neuropathologic hallmarks of Alzheimer's disease (AD) are extracellular Amyloid beta (Abeta) plaques and intracellular neurofibrillary tangles (NFTs). A number of additional pathogenic mechanisms, possibly overlapping with Abeta plaques and NFTs formation, have been described, including inflammation, oxidative damage, iron disregulation, cholesterol metabolism. The first drugs developed for AD, anticholinesterase inhibitors (AchEI), increase acetylcholine levels, previously demonstrated to be reduced in AD. To date, four AchEI are approved for the treatment of mild to moderate AD. A further therapeutic option available for moderate to severe AD is memantine. These treatments are symptomatic, whereas drugs under development are supposed to modify pathological steps leading to AD, thus acting on the evolution of the disease. For this reason they are currently termed "disease modifying" drugs. To block the progression of the disease, they have to interfere with pathogenic steps at the basis of clinical symptoms. In this review, current treatment will be summarized and new perspectives discussed. In particular, several approaches will be described, including Abeta deposition interference by Anti-Abeta aggregation agents, vaccination, gamma-secretase inhibition or Selective Abeta42 lowering agents (SALAs); tau deposition interference by methyl thioninium chloride (MTC); reduction of inflammation and oxidative damage. PMID- 20298172 TI - Breath holding index and arterial stiffness as markers of vascular aging. AB - BACKGROUND: The aim of the study was to evaluate correlation of breath holding index (BHI) as functional parameter for intracranial subclinical atherosclerotic changes - we have shown in our previous works and arterial stiffness (AS functional parameter for extracranial subclinical atherosclerotic changes) in normal population. PATIENTS AND METHODS: We included 120 healthy volunteers (conventional risk factors for cerebrovascular disease were excluded) who were examined at our Neurology Department. They were divided into 6 age groups-(25-35, 36-45, 46-55, 56-65, 66-75, 76+ years). We performed standard laboratory workup, body weight and height measurements, Color Doppler and Power Doppler of the main head and neck vessels and Transcranial Doppler, (measured by means of e-Tracking software). RESULTS: There was decline of BHI, and increase in AS - in correlation with age increase (p<0.01). There was statistically significant negative correlation between BHI and AS (r= -0,931, p<0.01 right and r = -0,938, p<0.01 left). CONCLUSION: These results show that decline in BHI as parameter for intracranial microvessel dysfunction is in good correlation with increase of AS as functional parameter of extracranial vascular aging. PMID- 20298173 TI - "Care-getting": a conceptual model of marshalling support near the end of life. AB - This paper offers a conceptual framework that focuses on "care-getting", a proactive means of insuring responsive and high quality care that is necessary for maintenance of good quality of life during the final years of life. Unlike traditional formulations and empirical studies that consider end of life issues among the terminally ill, we call for a broader consideration of the final years of life among older adults experiencing different health trajectories. We expect frail older adults' dispositions, proactive adaptations, and responsiveness of their informal and formal social resources, to play key roles in achieving good quality of life close to the end of life. Such positive outcomes near the end of life help preserve the integrity of the person and contribute to a sense of being cared for [1]. The conceptual framework we propose is a necessary next step for social gerontology, in order to incorporate preparation for dying into the life course. This important final life stage has been previously neglected in gerontological life course theory. Cross-cultural considerations in getting responsive care close to the end of life are discussed. PMID- 20298171 TI - Diet and neurocognition: review of evidence and methodological considerations. AB - The relationship between diet and cognitive function has been a topic of increasing interest, as numerous studies have shown that variations in dietary practices and nutrient intake may protect against age-related cognitive decline, as well as the development of dementia and Alzheimer's Disease (AD). Various dietary practices and specific nutrient components of these diets have been examined in relation to cognitive performance including 1) dietary fatty acids (including fish oil) and the Mediterranean diet, 2) antioxidants (including vitamins E and C) and fruits and vegetables, 3) vitamins B6, B12 (cobolamine), and folate, and, more recently, 4) caloric restriction. Although observational studies have generally reported significant associations between dietary practices and reduced incidence of cognitive dysfunction, randomized trials of dietary interventions have yielded mixed findings, with many trials yielding small gains or equivocal findings. In addition, findings appear to vary based on sample characteristics, methods of dietary assessment, and length of study follow up. The influence of dietary practices on cognitive function in middle aged and older adults remains uncertain, and further research is needed to clarify the nature of this relationship and identify mechanisms by which diet may affect neurocognition. PMID- 20298174 TI - Turning points in the life course: current findings and future directions in drug use research. AB - Turning point, a key concept in the developmental life course approach, is currently understudied in the field of substance abuse, but merits further research. A turning point often involves a particular event, experience, or awareness that results in changes in the direction of a pathway or persistent trajectory over the long-term. This article (1) provides an overview of the relevant literature on the concept of turning points from the life course and developmental criminology perspectives, (2) reviews literature on turning points in substance use, (3) discusses methodological considerations, and (4) suggests areas for future research on turning points in drug use. The influence of life course concepts related to drug use trajectories and turning points (including, for example, timing and sequencing of life events, individual characteristics, human agency, and social and historical context) offers a potentially fruitful area of investigation that may increase our understanding of why and how drug users stop and resume using over the long-term. Further research on turning points may be particularly valuable in unpacking the multifaceted and complex underlying mechanisms and factors involved in lasting changes in drug use. PMID- 20298175 TI - Barrett's metaplasia: molecular mechanisms and nutritional influences. AB - Barrett's metaplasia is discussed in the context of a general theory for the formation of metaplasias based on developmental biology. The phenotype of a particular tissue type becomes established during embryonic development by the expression of a specific set of transcription factors. If this combination becomes altered, then the tissue type can be altered. Such events may occur by mutation or by environmental effects on gene expression, normally within the stem cell population of the tissue. A macroscopic patch of metaplastic tissue will arise only if the new gene activity state is self-sustaining in the absence of its original causes, and if the new tissue type can outgrow the parent tissue type. An important candidate gene for the causation of Barrett's metaplasia is Cdx2 (Caudal-type homeobox 2). In normal development, this is expressed in the future intestine, but not the future foregut. Mouse knockout studies have shown that it is needed for intestinal development, and that its loss from adult intestine can lead to squamous transformations. It is also expressed in Barrett's metaplasia and can be activated in oesophageal cell cultures by treatment with bile acids. We have investigated the ability of Cdx2 to bring about intestinal transformations in oesophageal epithelium. Our results show that Cdx2 can activate a programme of intestinal gene expression when overexpressed in HET-1A cells, or in fetal epithelium, but not in the adult epithelium. This suggests that Cdx2, although necessary for formation of intestinal tissue, is not sufficient to provoke Barrett's metaplasia in adult life and that overexpression of additional transcription factors is necessary. In terms of diet and nutrition, there is a known association of Barrett's metaplasia with obesity. This may work through an increased risk of gastro-oesophageal reflux. Acid and bile are known to activate Cdx2 expression in oesophageal cells. It may also increase circulating levels of TNFalpha (tumour necrosis factor alpha), which activates Cdx2. In addition, there may be effects of diet on the composition of the bile. PMID- 20298176 TI - Modelling Barrett's oesophagus. AB - Barrett's oesophagus is the replacement of normal squamous oesophageal epithelium with an intestinalized columnar epithelium. Although some insight has been gained as to what Barrett's oesophagus is, how this columnar epithelium emerges from within a stratified squamous epithelium remains an unanswered question. We have sought to determine whether oesophageal keratinocytes can be trans-differentiated into Barrett's oesophagus cells. Using an Affymetrix microarray, we found unexpectedly that gene-expression patterns in the Barrett's oesophagus were only slightly more similar to the normal small intestine than they were to the normal oesophagus. Thus gene-expression patterns suggest significant molecular similarities remain between Barrett's oesophagus cells and normal squamous oesophageal epithelium, despite their histological resemblance with intestine. We next determined whether directed expression of intestine-specific transcription factors could induce intestinalization of keratinocytes. Retroviral-mediated Cdx2 (Caudal-type homeobox 2) expression in immortalized human oesophageal keratinocytes engineered with human telomerase reverse transcriptase (EPC2-hTERT cells) could be established transiently, but not maintained, and was associated with a reduction in cell proliferation. Co-expression of cyclin D1 rescued proliferation in the Cdx2-expressing cells, but co-expression of dominant negative p53 did not. Cdx2 expression in the EPC2-hTERT.D1 cells did not induce intestinalization. However, when combined with treatments that induce chromatin remodelling, there was a significant induction of Barrett's oesophagus-associated genes. Studies are ongoing to determine whether other intestinal transcription factors, either alone or in combination, can provoke greater intestinalization of oesophageal keratinocytes. We conclude that, on the basis of gene-expression patterns, Barrett's oesophagus epithelial cells may represent an intermediate between oesophageal keratinocytes and intestinal epithelial cells. Moreover, our findings suggest that it may be possible to induce Barrett's oesophagus epithelial cells from oesophageal keratinocytes by altering the expression of certain critical genes. PMID- 20298177 TI - Role of the micro-environment in Barrett's carcinogenesis. AB - Most epithelial cancers occur on the background of chronic exposure to damaging agents which is reflected in the long lag phase from development of a pre invasive lesion to the development of a carcinoma. Luminal refluxate has long been recognized to be associated with Barrett's oesophagus, although causal mechanisms have not been clearly defined. Recently, obesity and dietary nitric oxide have also been implicated in the disease pathogenesis. We have demonstrated that acid can alter cell kinetics and, together with nitric oxide, can induce double-stranded DNA breaks. Aside from exposure to luminal factors, the stromal micro-environment may also be important. There is increasing evidence to suggest that inflammatory pathways such as TGF (transforming growth factor) beta may play a role in Barrett's oesophagus carcinogenesis. Hence stromal-epithelial-luminal interactions may influence cell behaviour. As sequelae to this, it is possible that the niches created by the micro-environment may influence genetic epithelial diversity observed within the Barrett's oesophagus segment. PMID- 20298180 TI - Biomarkers in Barrett's oesophagus. AB - Biomarkers are needed to screen multiple stages in the clinical pathway of Barrett's oesophagus patients; from disease diagnosis to risk stratification and predicting response to therapy. Routes to the identification of biomarkers have been recognized by known molecular features of the disease and more recently through transcriptomic, methylation and proteomic screening approaches. The majority of Barrett's oesophagus patients remain undiagnosed in the general population. In order to develop a tool to screen for Barrett's oesophagus in the primary care setting, minimally invasive sampling methods coupled with immunocytology-based biomarkers are currently being assessed. Biomarkers may also have utility in surveillance programmes by allowing endoscopic interval to be adjusted according to individual neoplastic risk. Many individual biomarkers have been proposed in this regard, but have frequently been assessed in studies of limited power, or have lacked sufficient sensitivity or specificity when assessed in wider population-based studies. Biomarker panels may provide a route forward. In this regard, a panel of methylation markers has shown promise in a multicentre, double-blind, validation study. Biomarkers are also being developed to improve detection of high-grade dysplasia and oesophageal adenocarcinoma, utilizing brush cytology combined with FISH (fluorescence in situ hybridization), and to assess therapeutic success and risk of complication during photodynamic therapy. Finally, we outline progress in identifying alternative sources of biomarkers for this condition. PMID- 20298179 TI - The role of secondary bile acids in neoplastic development in the oesophagus. AB - Bile acids have been demonstrated, through the use of animal models and clinical association studies, to play a role in neoplastic development in Barrett's metaplasia. How specific bile acids promote neoplasia is as yet unknown, as are the exact identities of the important bile acid subtypes. The combination of bile subtype with appropriate pH is critical, as pH alters bile acid activity enormously. Hence glycine-conjugated bile acids are involved in neoplastic development at acidic pH (pH ~4), and unconjugated bile acids are involved in neoplastic development at more neutral pH (~6). Bile acids (at the appropriate pH) are potent DNA-damaging agents, due to the induction of ROS (reactive oxygen species), which are mainly induced by bile-induced damage to mitochondrial membranes, allowing leakage of ROS into the cytosol. These ROS also induce pro survival signalling pathways [e.g. via PKC (protein kinase C)-dependent NF-kappaB (nuclear factor kappaB) activity]. Interestingly, NOS (nitric oxide synthase), through induction of NO may exacerbate this NF-kappaB activity and form a positive-feedback loop to amplify the activation of NF-kappaB by deoxycholic acid in particular. This combination of induced DNA damage and cell survival by bile acids is of major importance in neoplasia. Antioxidants and the tertiary bile acid UDCA (ursodeoxycholic acid) can block bile-induced DNA damage and bile induced NF-kappaB activity, and should be considered in chemopreventative strategies. PMID- 20298178 TI - New models of neoplastic progression in Barrett's oesophagus. AB - Research in Barrett's oesophagus, and neoplastic progression to OAC (oesophageal adenocarcinoma), is hobbled by the lack of good pre-clinical models that capture the evolutionary dynamics of Barrett's cell populations. Current models trade off tractability for realism. Computational models are perhaps the most tractable and can be used both to interpret data and to develop intuitions and hypotheses for neoplastic progression. Tissue culture models include squamous cell lines, Barrett's oesophagus cell lines and OAC cell lines, although it was recognized recently that BIC-1, SEG-1 and TE-7 are not true OAC cell lines. Some of the unrealistic aspects of the micro-environment in two-dimensional tissue culture may be overcome with the development of three-dimensional organotypic cultures of Barrett's oesophagus. The most realistic, but least tractable, model is a canine surgical model that generates reflux and leads to an intestinal metaplasia. Alternatively, rat surgical models have gained popularity and should be tested for the common genetic features of Barrett's oesophagus neoplastic progression in humans including loss of CDKN2A (cyclin-dependent kinase inhibitor 2A) and TP53 (tumour protein 53), generation of aneuploidy and realistic levels of genetic diversity. This last feature will be important for studying the effects of cancer prevention interventions. In order to study the dynamics of progression and the effects of an experimental intervention, there is a need to follow animals longitudinally, with periodic endoscopic biopsies. This is now possible and represents an exciting opportunity for the future. PMID- 20298181 TI - The role of acid and bile reflux in oesophagitis and Barrett's metaplasia. AB - The precise mechanisms whereby gastro-oesophageal reflux disease causes reflux oesophagitis and Barrett's oesophagus are not clear, even though these diseases have been known to be linked for many years. Recent studies indicate a role for the reflux-induced inflammatory response of oesophageal squamous epithelial cells and the immune cells in the pathogenesis of reflux oesophagitis. Although reflux oesophagitis commonly heals with oesophageal squamous cell regeneration, in some individuals the oesophagus heals through the process of metaplasia, a condition termed Barrett's oesophagus. Recent studies indicate that individual differences in the reflux-mediated response of oesophageal squamous epithelial cells in the type of immune response and/or in signalling pathways that regulate cell proliferation or cell phenotype may determine whether the oesophagus heals with the regeneration of squamous cells or through Barrett's metaplasia. PMID- 20298182 TI - The role of Cdx genes in the gut and in axial development. AB - The Cdx (Caudal-type homeobox) group of ParaHox genes (Cdx1, Cdx2 and Cdx4 in the mouse) perform multiple functions in mammalian development. Cdx1 is concerned with axial positional information, and its deletion appears to have no important effect other than a disturbance of axial patterning. In contrast, Cdx2 is required for trophoblast differentiation, axial patterning and extension, as well as for morphological specification (i.e. patterning) of gut endoderm. Cdx4 knockout animals do not present an abnormal phenotype, but, when combined with Cdx2 haploinsufficiency, present a dramatic picture involving abnormal cloacal specification. The latter is probably due in large part to defective paraxial mesodermal development in the caudal region, but may also involve defective endodermal growth. A significant degree of redundancy is apparent between the Cdx genes with respect to caudal extension and possibly also during gut development. PMID- 20298183 TI - Pathophysiology of intestinal metaplasia of the stomach: emphasis on CDX2 regulation. AB - IM (intestinal metaplasia) of the stomach is a pre-neoplastic lesion that usually follows Helicobacter pylori infection and that confers increased risk for gastric cancer development. After setting the role played by CDX2 (Caudal-type homeobox 2) in the establishment of gastric IM, it became of foremost importance to unravel the regulatory mechanisms behind its de novo expression in the stomach. In the present paper, we review the basic pathology of gastric IM as well as the current knowledge on molecular pathways involved in CDX2 regulation in the gastric context. PMID- 20298184 TI - The role of Cdx2 in Barrett's metaplasia. AB - Metaplasia (or transdifferentiation) is defined as the transformation of one tissue type to another. Clues to the molecular mechanisms that control the development of metaplasia are implied from knowledge of the transcription factors that specify tissue identity during normal embryonic development. Barrett's metaplasia describes the development of a columnar/intestinal phenotype in the squamous oesophageal epithelium and is the major risk factor for oesophageal adenocarcinoma. This particular type of cancer has a rapidly rising incidence and a dismal prognosis. The homoeotic transcription factor Cdx2 (Caudal-type homeobox 2) has been implicated as a master switch gene for intestine and therefore for Barrett's metaplasia. Normally, Cdx2 expression is restricted to the epithelium of the small and large intestine. Loss of Cdx2 function, or conditional deletion in the intestine, results in replacement of intestinal cells with a stratified squamous phenotype. In addition, Cdx2 is sufficient to provoke intestinal metaplasia in the stomach. In the present paper, we review the evidence for the role of Cdx2 in the development of Barrett's metaplasia. PMID- 20298185 TI - Cellular origin of Barrett's metaplasia and oesophageal stem cells. AB - Barrett's oesophagus is a metaplastic pre-malignant disorder and the only established precursor lesion for oesophageal adenocarcinoma. Barrett's oesophagus develops when the normal stratified squamous epithelium of the lower oesophagus is replaced by a columnar lined mucosa with intestinal differentiation, usually in the context of chronic gastro-oesophageal reflux disease. The cellular and molecular mechanisms by which this metaplastic transformation occurs are poorly understood. Abnormal differentiation of multipotent stem cells in the squamous oesophagus, triggered by exposure to refluxate, is one potential mechanism. These stem cells could be located in the basal layer of the squamous oesophageal epithelium and/or in the neck region of the oesophageal submucosal gland ducts; however, their exact location and identification are still matter of discussion. Three-dimensional models combined with state-of-the-art imaging techniques are now applied to characterize the squamous epithelium in human oesophageal samples, and this could unveil essential information to identify these progenitor cells. Locating stem cells in human squamous oesophagus could have important implications for our understanding of Barrett's oesophagus and remarkably improve our future strategies for its prevention. PMID- 20298186 TI - Genetic diversity during the development of Barrett's oesophagus-associated adenocarcinoma: how, when and why? AB - Recent investigations into Barrett's oesophagus at the level of individual crypts have found significant genetic heterogeneity within a single lesion. Furthermore, this genetic diversity has been shown to predict cancer development. In the present article, we review the genetic alterations implicated in disease progression in Barrett's oesophagus and discuss how genetic diversity could arise during tumorigenesis. Three arguments are discussed: a high mutation rate coupled with strong selection, clonal interaction driving progression, and a hitherto unidentified alteration that disrupts epithelial cell homoeostasis. Suggestions are made for future research to distinguish which of these theories is the predominant mechanism in Barrett's oesophagus-associated tumorigenesis. PMID- 20298187 TI - Machines on genes: enzymes that make, break and move DNA and RNA. AB - As the vital information repositories of the cell, the nucleic acids DNA and RNA pose many challenges as enzyme substrates. To produce, maintain and repair DNA and RNA, and to extract the genetic information that they encode, a battery of remarkable enzymes has evolved, which includes translocases, polymerases/replicases, helicases, nucleases, topoisomerases, transposases, recombinases, repair enzymes and ribosomes. An understanding of how these enzymes function is essential if we are to have a clear view of the molecular biology of the cell and aspire to manipulate genomes and gene expression to our advantage. To bring together scientists working in this fast-developing field, the Biochemical Society held a Focused Meeting, 'Machines on Genes: Enzymes that Make, Break and Move DNA and RNA', at Robinson College, University of Cambridge, U.K., in August 2009. The present article summarizes the research presented at this meeting and the reviews associated with the talks which are published in this issue of Biochemical Society Transactions. PMID- 20298188 TI - Orchestrating serine resolvases. AB - A remarkable feature of the serine resolvases is their regulation: the wild-type enzymes will catalyse intra- but not inter-molecular recombination, can sense the relative orientation of their sites and can exchange strands directionally, despite the fact that there is no net release of chemical bond energy. The key to this regulation is that they are only active within a large intertwined complex called the 'synaptosome'. Because substrate topology greatly facilitates (or, in other cases, inhibits) formation of the synaptosome, it acts as a 'topological filter'. Within the defined topology of the synaptosome, strand exchange releases supercoiling tension, providing an energy source to bias the reaction direction. The regulatory portion of this complex contains additional copies of the recombinase and sometimes other DNA-bending proteins. We are using a combination of X-ray crystallography, biochemistry and genetics to model the full synaptic complex and to understand how the regulatory portion activates the crossover-site bound recombinases. PMID- 20298189 TI - Site-specific recombination by phiC31 integrase and other large serine recombinases. AB - Most temperate phages encode an integrase for integration and excision of the prophage. Integrases belong either to the lambda Int family of tyrosine recombinases or to a subgroup of the serine recombinases, the large serine recombinases. Integration by purified serine integrases occurs efficiently in vitro in the presence of their cognate (~50 bp) phage and host attachment sites, attP and attB respectively. Serine integrases require an accessory protein, Xis, to promote excision, a reaction in which the products of the integration reaction, attL and attR, recombine to regenerate attP and attB. Unlike other directional recombinases, serine integrases are not controlled by proteins occupying accessory DNA-binding sites. Instead, it is thought that different integrase conformations, induced by binding to the DNA substrates, control protein-protein interactions, which in turn determine whether recombination proceeds. The present review brings together the evidence for this model derived from the studies on phiC31 integrase, Bxb1 integrase and other related proteins. PMID- 20298190 TI - The Escherichia coli DNA translocase FtsK. AB - Escherichia coli FtsK is a septum-located DNA translocase that co-ordinates the late stages of cytokinesis and chromosome segregation. Relatives of FtsK are present in most bacteria; in Bacillus subtilis, the FtsK orthologue, SpoIIIE, transfers the majority of a chromosome into the forespore during sporulation. DNA translocase activity is contained within a ~ 512-amino-acid C-terminal domain, which is divided into three subdomains: alpha, beta and gamma. alpha and beta comprise the translocation motor, and gamma is a regulatory domain that interacts with DNA and with the XerD recombinase. In vitro rates of translocation of ~ 5 kb.s(-1) have been measured for both FtsK and SpoIIIE, whereas, in vivo, SpoIIIE has a comparable rate of translocation. Translocation by both of these proteins is not only rapid, but also directed by DNA sequence. This directionality requires interaction of the gamma subdomain with specific 8 bp DNA asymmetric sequences that are oriented co-directionally with replication direction of the bacterial chromosome. The gamma subdomain also interacts with the XerCD site specific recombinase to activate chromosome unlinking by recombination at the chromosomal dif site. In the present paper, the properties in vivo and in vitro of FtsK and its relatives are discussed in relation to the biological functions of these remarkable enzymes. PMID- 20298191 TI - The interaction of four-way DNA junctions with resolving enzymes. AB - Four-way DNA (Holliday) junctions are resolved into duplex species by the action of the junction-resolving enzymes, nucleases selective for the structure of helical branchpoints. These have been isolated from bacteria and their phages, archaea, yeasts and mammals, including humans. They are all dimeric proteins that bind with high selectivity to DNA junctions and generate bilateral cleavage within the lifetime of the DNA-protein complex. Recent success in obtaining X-ray crystal structures of resolving enzymes bound to DNA junctions has revealed how the structural selectivity of these enzymes is achieved. PMID- 20298193 TI - The type IIB restriction endonucleases. AB - The endonucleases from the Type IIB restriction-modification systems differ from all other restriction enzymes. The Type IIB enzymes cleave both DNA strands at specified locations distant from their recognition sequences, like Type IIS nucleases, but they are unique in that they do so on both sides of the site, to liberate the site from the remainder of the DNA on a short duplex. The fact that these enzymes cut DNA at specific locations mark them as Type II systems, as opposed to the Type I enzymes that cut DNA randomly, but in terms of gene organization and protein assembly, most Type IIB restriction-modification systems have more in common with Type I than with other Type II systems. Our current knowledge of the Type IIB systems is reviewed in the present paper. PMID- 20298192 TI - Maintaining a sense of direction during long-range communication on DNA. AB - Many biological processes rely on the interaction of proteins with multiple DNA sites separated by thousands of base pairs. These long-range communication events can be driven by both the thermal motions of proteins and DNA, and directional protein motions that are rectified by ATP hydrolysis. The present review describes conflicting experiments that have sought to explain how the ATP dependent Type III restriction-modification enzymes can cut DNA with two sites in an inverted repeat, but not DNA with two sites in direct repeat. We suggest that an ATPase activity may not automatically indicate a DNA translocase, but can alternatively indicate a molecular switch that triggers communication by thermally driven DNA sliding. The generality of this mechanism to other ATP dependent communication processes such as mismatch repair is also discussed. PMID- 20298194 TI - Catalysis of site-specific recombination by Tn3 resolvase. AB - The active-site interactions involved in the catalysis of DNA site-specific recombination by the serine recombinases are still incompletely understood. Recent crystal structures of synaptic gammadelta resolvase-DNA intermediates and biochemical analysis of Tn3 resolvase mutants have provided new insights into the structure of the resolvase active site, and how interactions of the catalytic residues with the DNA substrate might promote the phosphoryl transfer reactions. PMID- 20298195 TI - Ancient machinery embedded in the contemporary ribosome. AB - Structural analysis, supported by biochemical, mutagenesis and computational evidence, indicates that the peptidyltransferase centre of the contemporary ribosome is a universal symmetrical pocket composed solely of rRNA. This pocket seems to be a relic of the proto-ribosome, an ancient ribozyme, which was a dimeric RNA assembly formed from self-folded RNA chains of identical, similar or different sequences. This could have occurred spontaneously by gene duplication or gene fusion. This pocket-like entity was capable of autonomously catalysing various reactions, including peptide bond formation and non-coded or semi-coded amino acid polymerization. Efforts toward the structural definition of the early entity capable of genetic decoding involve the crystallization of the small ribosomal subunit of a bacterial organism harbouring a single functional rRNA operon. PMID- 20298196 TI - Nanomechanical constraints acting on the catalytic site of cellular RNA polymerases. AB - RNAPs (RNA polymerases) are complex molecular machines containing structural domains that co-ordinate the movement of nucleic acid and nucleotide substrates through the catalytic site. X-ray images of bacterial, archaeal and eukaryotic RNAPs have provided a wealth of structural detail over the last decade, but many mechanistic features can only be derived indirectly from such structures. We have therefore implemented a robotic high-throughput structure-function experimental system based on the automatic generation and assaying of hundreds of site directed mutants in the archaeal RNAP from Methanocaldococcus jannaschii. In the present paper, I focus on recent insights obtained from applying this experimental strategy to the bridge-helix domain. Our work demonstrates that the bridge-helix undergoes substantial conformational changes within a narrowly confined region (mjA' Ala(822)-Gln(823)-Ser(824)) during the nucleotide-addition cycle. Naturally occurring radical sequence variations in plant RNAP IV and V enzymes map to this region. In addition, many mutations within this domain cause a substantial increase in the RNAP catalytic activity ('superactivity'), suggesting that the RNAP active site is conformationally constrained. PMID- 20298197 TI - Substrate recognition and catalysis by flap endonucleases and related enzymes. AB - FENs (flap endonucleases) and related FEN-like enzymes [EXO-1 (exonuclease-1), GEN-1 (gap endonuclease 1) and XPG (xeroderma pigmentosum complementation group G)] are a family of bivalent-metal-ion-dependent nucleases that catalyse structure-specific hydrolysis of DNA duplex-containing nucleic acid structures during DNA replication, repair and recombination. In the case of FENs, the ability to catalyse reactions on a variety of substrates has been rationalized as a result of combined functional and structural studies. Analyses of FENs also exemplify controversies regarding the two-metal-ion mechanism. However, kinetic studies of T5FEN (bacteriophage T5 FEN) reveal that a two-metal-ion-like mechanism for chemical catalysis is plausible. Consideration of the metallobiochemistry and the positioning of substrate in metal-free structures has led to the proposal that the duplex termini of substrates are unpaired in the catalytically active form and that FENs and related enzymes may recognize breathing duplex termini within more complex structures. An outstanding issue in FEN catalysis is the role played by the intermediate (I) domain arch or clamp. It has been proposed that FENs thread the 5'-portion of their substrates through this arch, which is wide enough to accommodate single-stranded, but not double stranded, DNA. However, FENs exhibit gap endonuclease activity acting upon substrates that have a region of 5'-duplex. Moreover, the action of other FEN family members such as GEN-1, proposed to target Holliday junctions without termini, appears incompatible with a threading mechanism. An alterative is that the I domain is used as a clamp. A future challenge is to clarify the role of this domain in FENs and related enzymes. PMID- 20298198 TI - The role of ATP in the reactions of type II DNA topoisomerases. AB - Type II DNA topoisomerases catalyse changes in DNA topology in reactions coupled to the hydrolysis of ATP. In the case of DNA gyrase, which can introduce supercoils into DNA, the requirement for free energy is clear. However, the non supercoiling type II enzymes carry out reactions that are apparently energetically favourable, so their requirement for ATP hydrolysis is not so obvious. It has been shown that many of these enzymes (the type IIA family) can simplify the topology of their DNA substrates to a level beyond that expected at equilibrium. Although this seems to explain their usage of ATP, we show that the free energies involved in topology simplification are very small (<0.2% of that available from ATP) and we argue that topology simplification may simply be an evolutionary relic. PMID- 20298199 TI - Synaptopathy: dysfunction of synaptic function? AB - Synaptopathy is an increasingly popular term used to define key features of neurodegenerative and psychiatric disease. It implies that disruptions in synaptic structure and function are potentially the major determinant of such brain diseases. The Synaptopathies: Dysfunction of Synaptic Function Biochemical Society Focused Meeting brought together several invited speakers, supplemented with short communications from young scientists, who addressed this possibility. The talks spanned the full gamut of approaches that brought molecular, cellular, systems and whole-animal experimentation together to address how fundamental synaptic biology was increasingly informing on dysfunction in disease. The disease and models thereof discussed included Alzheimer's disease, prions, Huntington's disease, Parkinson's disease, schizophrenia and autism. The audience were asked to reflect on whether synaptopathy, although attractive and conceptually useful, provided a significant explanation as the cause of these major diseases. The breadth of the meeting reinforced the complexity of these brain diseases, supported the significance of synaptic dysfunction in disease, but left open the issue as to whether the prime cause of these disorders could be resolved as simple synaptic dysfunction. Thus, despite revealing a value of synaptopathy, further investigation will be required to reveal its balance in the cause and effect in each of the major brain diseases. PMID- 20298200 TI - Confirmed rare copy number variants implicate novel genes in schizophrenia. AB - Understanding how cognitive processes including learning, memory, decision making and ideation are encoded by the genome is a key question in biology. Identification of sets of genes underlying human mental disorders is a path towards this objective. Schizophrenia is a common disease with cognitive symptoms, high heritability and complex genetics. We have identified genes involved with schizophrenia by measuring differences in DNA copy number across the entire genome in 91 schizophrenia cases and 92 controls in the Scottish population. Our data reproduce rare and common variants observed in public domain data from >3000 schizophrenia cases, confirming known disease loci as well as identifying novel loci. We found copy number variants in PDE10A (phosphodiesterase 10A), CYFIP1 [cytoplasmic FMR1 (Fragile X mental retardation 1)-interacting protein 1], K(+) channel genes KCNE1 and KCNE2, the Down's syndrome critical region 1 gene RCAN1 (regulator of calcineurin 1), cell recognition protein CHL1 (cell adhesion molecule with homology with L1CAM), the transcription factor SP4 (specificity protein 4) and histone deacetylase HDAC9, among others (see http://www.genes2cognition.org/SCZ-CNV). Integrating the function of these many genes into a coherent model of schizophrenia and cognition is a major unanswered challenge. PMID- 20298201 TI - TorsinA and DYT1 dystonia: a synaptopathy? AB - DYT1 dystonia is an autosomal dominant movement disorder, characterized by early onset of involuntary sustained muscle contractions. It is caused by a 3-bp deletion in the DYT1 gene, which results in the deletion of a single glutamate residue in the C-terminus of the protein TA (torsinA). TA is a member of the AAA+ (ATPase associated with various cellular activities) family of chaperones with multiple functions in the cell. There is no evidence of neurodegeneration in DYT1 dystonia, which suggests that mutant TA leads to functional neuronal abnormalities, leading to dystonic movements. In recent years, different functional roles have been attributed to TA, including being a component of the cytoskeleton and the NE (nuclear envelope), and involvement in the secretory pathway and SV (synaptic vesicle) machinery. The aim of the present review is to summarize these findings and the different models proposed, which have contributed to our current understanding of the function of TA, and also to discuss the evidence implicating TA in SV function. PMID- 20298202 TI - Stochastic aspects of transmitter release and bioenergetic dysfunction in isolated nerve terminals. AB - Synaptosomes (isolated nerve terminals) have been studied for more than 40 years. The preparation allows aspects of transmitter metabolism and release to be studied ex vivo from specific brain regions of animals of any age. Conditions can be devised to enable the terminals to fire spontaneous action potentials, allowing the presynaptic control of glutamate exocytosis to be studied. Recent developments have greatly increased the sensitivity with which the bioenergetics of the intra-synaptosomal mitochondria can be investigated. PMID- 20298203 TI - Endosomal sorting of AMPA receptors in hippocampal neurons. AB - An important mechanism for the regulation of excitatory synaptic transmission in the hippocampus involves tight control of AMPAR [AMPA (alpha-amino-3-hydroxy-5 methylisoxazole-4-propionic acid) receptor] trafficking to alter the number or subtype of synaptic receptors. This is achieved via the multiple stages of the endosomal system. AMPARs constitutively cycle through early endosomes and recycling endosomes to maintain synaptic receptor numbers. However, on induction of synaptic plasticity, subtle alterations are made to this cycle by the action of specific AMPAR-interacting proteins and also via a number of additional proteins that regulate endosomal sorting more generally. During long-term depression, receptors are diverted to late endosomes and lysosomes rather than recycling back to the plasma membrane, hence reducing the number of receptors at the synapse. The increased number of synaptic AMPARs after induction of LTP (long term potentiation) originates from the recycling compartment. In addition, transient changes in subunit composition may arise as a result of retention of AMPAR subtypes within the endosome during LTP. Aberrant trafficking after pathological insults such as oxygen/glucose deprivation or mechanical trauma also involves alterations in synaptic AMPAR subunit composition, leading to calcium influx that ultimately results in cell death. PMID- 20298204 TI - Drug targets for amyloidosis. AB - The amyloid hypothesis indicates that protein misfolding is at the root of many neurodegenerative disorders. Small molecules targeting the formation, clearance, aggregation to toxic oligomers or SOD (superoxide dismutase)-like activities of Abeta (amyloid beta-peptide) 1-42 have provided encouraging candidates for AD (Alzheimer's disease) medicines in animal models, although none have yet proved to be effective in human trials. We have been investigating approaches to treat systemic amyloidoses, conditions that show common features with some CNS (central nervous system) disorders. For TTR (transthyretin) amyloidosis, we are seeking small molecule compounds that stabilize the amyloidogenic protein and either prevent its structural transition to the crossed beta fibres deposited in diseased tissues, or promote its clearance from circulation. Effective stabilizer compounds that simultaneously bind to both thyroxine-binding sites have been developed. A more generic approach involves targeting the plasma glycoprotein SAP (serum amyloid P component). This protein recognizes the misfolded polypeptide structures of amyloid deposits wherever they occur, and acts as a powerful anti opsonin. We have developed a bivalent drug called CPHPC {(R)-1-[6-[(R)-2-carboxy pyrrolidin-1-yl]-6-oxo-hexanoyl]-pyrrolidine-2-carboxylic acid} that cross-links pairs of pentameric SAP molecules and causes their rapid elimination from the circulation. This strategy raises the prospect of encouraging natural mechanisms to clear amyloid and recent work suggests that this approach extends to the CNS. PMID- 20298205 TI - Reactive hypertrophy of synaptic varicosities within the hippocampus of prion infected mice. AB - Prion diseases are characteristically accompanied by extensive synaptic pathology that can occur during the preclinical phase of the disease and, in animal models, correlates with the first decline of hippocampus-dependent cognitive functions. This pathology is defined by abnormally shaped synapses in which the postsynaptic membrane modifies its curvature and potentially engulfs the juxtaposed presynaptic membrane. Using the intrahippocampally injected ME7 prion model, we further detailed the structural alterations of the population of ostensibly intact synaptic compartments within the hippocampus during this period of extensive synaptic loss. A disease stage-dependent increase in the average PSD (postsynaptic density) area, the average length of the active zone and the average number of synaptic vesicles indicated that the synapses that were visualized as the animal progressed to end-stage disease were undergoing hypertrophy. Similar findings in samples from AD (Alzheimer's disease) patients, aged and senile individuals, and animal models of neurodegenerative diseases suggest synaptic swelling as synaptic loss is initiated and/or compensatory reaction to counteract the synaptic loss. PMID- 20298206 TI - Synapse elimination during development and disease: immune molecules take centre stage. AB - Synapse elimination is a normal developmental process occurring throughout the central and peripheral nervous systems. Meanwhile, gradual and early loss of synapses is a characteristic that is common to several neurodegenerative disease states. Recent evidence has emerged implicating molecules canonically involved in the immune system and inflammation accompanying neurodegeneration (e.g. classical complement cascade) as important players in the normal elimination of synapses in the developing nervous system. As a result, a question has emerged as to whether mechanisms underlying elimination of synapses during normal development are recapitulated and contribute to early synapse loss and nervous system dysfunction during neurodegenerative disease. The present review explores this possibility and provides a description of many neuroimmune proteins that may participate in the elimination of synapses and synaptic dysfunction in the developing and diseased brain. PMID- 20298207 TI - Dysfunction and recovery of synapses in prion disease: implications for neurodegeneration. AB - Synaptic dysfunction is a key early process in many neurodegenerative diseases, but how this ultimately leads to neuronal loss is not clear. In health, there is ongoing remodelling of synapses and spines in the adult brain: their elimination and formation are continual physiological processes fundamental to learning and memory. But in neurodegenerative disease, including prion disease, lost synapses are not replaced, and their loss is followed by neuronal death. These two processes are separately regulated, with mechanistic, spatial and temporal segregation of the respective death routines of synapses and cell bodies. Mice with prion disease can be cured at the stage of early synaptic dysfunction, when they have reversible impairments at neurophysiological, behavioural and morphological levels. Critically, reversing synaptic dysfunction at this stage of disease rescues neurons, preventing its otherwise inevitable progression to synapse loss and cell death. These findings call for a deeper analysis of the mechanisms underlying neurotoxicity at the synapse, and have important implications for the therapy of prion and other neurodegenerative disorders. PMID- 20298208 TI - Presynaptic dysfunction in Huntington's disease. AB - HD (Huntington's disease) is produced by the expression of mutant forms of the protein htt (huntingtin) containing a pathologically expanded poly-glutamine repeat. For unknown reasons, in HD patients and HD mouse models, neurons from the striatum and cerebral cortex degenerate and lead to motor dysfunction and dementia. Synaptic transmission in those neurons becomes progressively altered during the course of the disease. However, the relationship between synaptic dysfunction and neurodegeneration in HD is not yet clear. Are there early specific functional synaptic changes preceding symptoms and neurodegeneration? What is the role of those changes in neuronal damage? Recent experiments in a Drosophila model of HD have showed that abnormally increased neurotransmitter release might be a leading cause of neurodegeneration. In the present review, we summarize recently described synaptic alterations in HD animal models and discuss potential underlying molecular mechanisms. PMID- 20298209 TI - Synaptic dysfunction in Parkinson's disease. AB - In neuronal circuits, memory storage depends on activity-dependent modifications in synaptic efficacy, such as LTD (long-term depression) and LTP (long-term potentiation), the two main forms of synaptic plasticity in the brain. In the nucleus striatum, LTD and LTP represent key cellular substrates for adaptive motor control and procedural memory. It has been suggested that their impairment could account for the onset and progression of motor symptoms of PD (Parkinson's disease), a neurodegenerative disorder characterized by the massive degeneration of dopaminergic neurons projecting to the striatum. In fact, a peculiar aspect of striatal plasticity is the modulation exerted by DA (dopamine) on LTP and LTD. Our understanding of these maladaptive forms of plasticity has mostly come from the electrophysiological, molecular and behavioural analyses of experimental animal models of PD. In PD, a host of cellular and synaptic changes occur in the striatum in response to the massive loss of DA innervation. Chronic L-dopa therapy restores physiological synaptic plasticity and behaviour in treated PD animals, but most of them, similarly to patients, exhibit a reduction in the efficacy of the drug and disabling AIMs (abnormal involuntary movements) defined, as a whole, as L-dopa-induced dyskinesia. In those animals experiencing AIMs, synaptic plasticity is altered and is paralleled by modifications in the postsynaptic compartment. In particular, dysfunctions in trafficking and subunit composition of NMDARs [NMDA (N-methyl-D-aspartate) receptors] on striatal efferent neurons result from chronic non-physiological dopaminergic stimulation and contribute to the pathogenesis of dyskinesias. According to these pathophysiological concepts, therapeutic strategies targeting signalling proteins coupled to NMDARs within striatal spiny neurons could represent new pharmaceutical interventions for PD and L-dopa-induced dyskinesia. PMID- 20298210 TI - Reversibility of functional deficits in experimental models of Rett syndrome. AB - Mutations in the X-linked MECP2 gene are the primary cause of the severe autism spectrum disorder RTT (Rett syndrome). Deletion of Mecp2 in mice recapitulates many of the overt neurological features seen in humans, and the delayed onset of symptoms is accompanied by deficits in neuronal morphology and synaptic physiology. Recent evidence suggests that reactivation of endogenous Mecp2 in young and adult mice can reverse aspects of RTT-like pathology. In the current perspective, we discuss these findings as well as other genetic, pharmacological and environmental interventions that attempt phenotypic rescue in RTT. We believe these studies provide valuable insights into the tractability of RTT and related conditions and are useful pointers for the development of future therapeutic strategies. PMID- 20298211 TI - The developmental roles of FMRP. AB - FXS (Fragile X syndrome) is the most common genetically inherited form of cognitive impairment. The predominant cause of the syndrome is the loss of a single protein, FMRP (Fragile X mental retardation protein). Many of the cognitive and behavioural features found in Fragile X individuals emerge during childhood and are associated with abnormal organization of cortical connections. However, although FMRP is expressed as early as embryogenesis, relatively little is known about its roles during development or how this may influence FXS phenotypes in adulthood. The present review focuses specifically on the evidence for the functions of FMRP during embryonic and early postnatal development. The current knowledge of the role of FMRP in FXS will be briefly summarized before addressing how alterations in the formation and refinement of neuronal connections and synaptic function that result from the loss of FMRP may in turn influence behaviours that are expressed during the first few postnatal weeks. I will then briefly highlight some outstanding questions about the developmental roles of FMRP and their possible relationship to symptoms found in adults with FXS. PMID- 20298212 TI - 'Holistic' synaptogenesis. AB - Synapses between nerve cells in the mammalian brain are not only extremely numerous but also very diverse with respect to their structural and functional characteristics. This heterogeneity arises despite the fact that a set of common basic protein 'building blocks' is shared by many synapses. Among these, postsynaptic scaffolding proteins play a key role. They have the ability to assemble into membrane-tethered lattices and to adopt unique conformational states in different postsynaptic microenvironments, which may represent a key prerequisite of synapse heterogeneity. Analyses of such synaptic superstructures, rather than individual proteins and their interactions, are required to develop a mechanistic understanding of postsynaptic differentiation, synapse diversity, and dynamics. PMID- 20298213 TI - Errant ensembles: dysfunctional neuronal network dynamics in schizophrenia. AB - Most complex psychiatric disorders cannot be explained by pathology of a single brain region, but arise as a consequence of dysfunctional interactions between brain regions. Schizophrenia, in particular, has been described as a 'disconnection syndrome', but similar principles are likely to apply to depression and ADHD (attention deficit hyperactivity disorder). All these diseases are associated with impaired co-ordination of neural population activity, which manifests as abnormal EEG (electroencephalogram) and LFP (local field potential) oscillations both within and across subcortical and cortical brain regions. Importantly, it is increasingly possible to link oscillations and interactions at distinct frequencies to the physiology and/or pathology of distinct classes of neurons and interneurons. Such analyses increasingly implicate abnormal levels, timing or modulation of GABA (gamma-aminobutyric acid) ergic inhibition in brain disease. The present review discusses the evidence suggesting that dysfunction of a particular class of interneurons, marked by their expression of the calcium-binding protein parvalbumin, could contribute to the broad range of neurophysiological and behavioural symptoms characteristic of schizophrenia. PMID- 20298214 TI - S-acylation by the DHHC protein family. AB - A family of 23 DHHC (Asp-His-His-Cys) proteins that function as mammalian S acyltransferases has been identified, reinvigorating the study of protein S acylation. Recent studies have continued to reveal how S-acylation affects target proteins, and have provided glimpses of how DHHC-substrate specificity might be achieved. PMID- 20298215 TI - The anti-allodynic alpha(2)delta ligand pregabalin inhibits the trafficking of the calcium channel alpha(2)delta-1 subunit to presynaptic terminals in vivo. AB - Neuropathic pain is caused by lesion or dysfunction of the peripheral sensory nervous system. Up-regulation of the voltage-gated Ca(2+) channel subunit alpha(2)delta-1 in DRG (dorsal root ganglion) neurons and the spinal cord correlates with the onset of neuropathic pain symptoms such as allodynia in several animal models of neuropathic pain. The clinically important anti allodynic drugs gabapentin and pregabalin are alpha(2)delta-1 ligands, but how these drugs alleviate neuropathic pain is poorly understood. In the present paper, we review recent advances in our understanding of their molecular mechanisms. PMID- 20298216 TI - Presynaptic roles of intracellular Ca(2+) stores in signalling and exocytosis. AB - The signalling roles of Ca(2+)(ic) (intracellular Ca(2+)) stores are well established in non-neuronal and neuronal cells. In neurons, although Ca(2+)(ic) stores have been assigned a pivotal role in postsynaptic responses to G(q) coupled receptors, or secondarily to extracellular Ca(2+) influx, the functions of dynamic Ca(2+)(ic) stores in presynaptic terminals remain to be fully elucidated. In the present paper, we review some of the recent evidence supporting an involvement of Ca(2+)(ic) in presynaptic function, and discuss loci at which this source of Ca(2+) may impinge. Nerve terminal preparations provide good models for functionally examining putative Ca(2+)(ic) stores under physiological and pathophysiological stimulation paradigms, using Ca(2+) dependent activation of resident protein kinases as sensors for fine changes in intracellular Ca(2+) levels. We conclude that intraterminal Ca(2+)(ic) stores may, directly or indirectly, enhance neurotransmitter release following nerve terminal depolarization and/or G-protein-coupled receptor activation. During conditions that prevail following neuronal ischaemia, increased glutamate release instigated by Ca(2+)(ic) store activation may thereby contribute to excitotoxicity and eventual synaptopathy. PMID- 20298217 TI - Are synapses targets of nanoparticles? AB - The last few years have been marked by real breakthroughs in the field of nanotechnology. Application of nanoparticles was proposed for diagnosis and treatment of different central nervous system diseases. Exposure to nanoparticles in vivo increases the risk of onset of neurodegenerative diseases and nanoparticles are apparently able to kill neurons in vitro. We suggested that presynaptic terminals of neurons are another target for nanoparticles, beyond the already established microglial cells. Ferritin was chosen as a prototypic nanoparticle model. We found that even a high concentration of ferritin, 800 microg/ml, was not able to induce spontaneous release of [(14)C]glutamate. In contrast, [(14)C]glutamate uptake was inhibited by ferritin in a dose-dependent fashion. As a next step, the influence of ferritin on the formation of reactive oxygen species was monitored using the fluorescent dye DCFH-DA (2',7' dichlorofluorescein diacetate). It was shown that ferritin leads to a dose dependent formation of free radicals. We found that the ferritin-mediated changes in glutamatergic neurotransmission at presynaptic endings can result in neuronal damage and finally neurodegeneration. PMID- 20298218 TI - Alzheimer's disease and amyloid beta-peptide deposition in the brain: a matter of 'aging'? AB - Biomolecules can experience aging processes that limit their long-term functionality in organisms. Typical markers of protein aging are spontaneous chemical modifications, such as AAR (amino acid racemization) and AAI (amino acid isomerization), mainly involving aspartate and asparagine residues. Since these modifications may affect folding and turnover, they reduce protein functionality over time and may be linked to pathological conditions. The present mini-review describes evidence of AAR and AAI involvement in the misfolding and brain accumulation of Abeta (amyloid beta-peptide), a central event in AD (Alzheimer's disease) synaptic dysfunctions. Structural alterations introduced by site specific modifications linked to protein aging may affect Abeta production, polymerization and clearance, and therefore play a pivotal role in the pathogenesis of sporadic and genetic forms of AD. Early changes associated with molecular aging also have significant long-term consequences for Abeta folding and turnover. New fast, reproducible and accurate methods for the screening of protein aging markers in biological samples may contribute to improve diagnostic and therapeutic approaches in AD. PMID- 20298219 TI - Change in tau phosphorylation associated with neurodegeneration in the ME7 model of prion disease. AB - Hyperphosphorylation of the microtubule-associated protein tau is a significant determinant in AD (Alzheimer's disease), where it is associated with disrupted axonal transport and probably causes synaptic dysfunction. Although less well studied, hyperphosphorylation has been observed in prion disease. We have investigated the expression of hyperphosphorylated tau in the hippocampus of mice infected with the ME7 prion agent. In ME7-infected animals, there is a selective loss of CA1 synapse, first discernable at 13 weeks of disease. There is a potential that dysfunctional axonal transport contributes to this synaptopathy. Thus investigating hyperphosphorylated tau that is dysfunctional in AD could illuminate whether and how they are significant in prion disease. We observed no differences in the levels of phosphorylated tau (using MC1, PHF-1 and CP13 antibodies) in detergent-soluble and detergent-insoluble fractions extracted from ME7- and NBH- (normal brain homogenate) treated animals across disease. In contrast, we observed an increase in phospho-tau staining for several epitopes using immunohistochemistry in ME7-infected hippocampal sections. Although the changes were not of the magnitude seen in AD tissue, clear differences for several phospho-tau species were seen in the CA1 and CA3 of ME7-treated animals (pSer(199-202)>pSer(214)>PHF-1 antibody). Temporally, these changes were restricted to animals at 20 weeks and none of the disease-related staining was associated with the axons or dendrites that hold CA1 synapses. These findings suggest that phosphorylation of tau at the epitopes examined does not underpin the early synaptic dysfunction. These data suggest that the changes in tau phosphorylation recorded here and observed by others relate to end-stage prion pathology when early dysfunctions have progressed to overt neuronal loss. PMID- 20298220 TI - Metallothioneins and copper metabolism are candidate therapeutic targets in Huntington's disease. AB - HD (Huntington's disease) is caused by a polyQ (polyglutamine) expansion in the huntingtin protein, which leads to protein misfolding and aggregation of this protein. Abnormal copper accumulation in the HD brain was first reported more than 15 years ago. Recent findings show that copper-regulatory genes are induced during HD and copper binds to an N-terminal fragment of huntingtin, supporting the involvement of abnormal copper metabolism in HD. We have demonstrated that in vitro copper accelerates the fibrillization of an N-terminal fragment of huntingtin with an expanded polyQ stretch (httExon1). As we found that copper also increases polyQ aggregation and toxicity in mammalian cells expressing httExon1, we investigated further whether overexpression of genes involved in copper metabolism, notably MTs (metallothioneins) known to bind copper, protect against httExon1 toxicity. Using a yeast model of HD, we have shown that overexpression of several genes involved in copper metabolism reduces polyQ mediated toxicity. Overexpression of MT-3 in mammalian cells significantly reduced polyQ aggregation and toxicity. We propose that copper-binding and/or chaperoning proteins, especially MTs, are potential therapeutic targets for HD. PMID- 20298221 TI - Caenorhabditis elegans: a useful tool to decipher neurodegenerative pathways. AB - Neurodegenerative disorders such as Alzheimer's, Parkinson's and Huntington's diseases affect millions of people. These disorders are age-dependent, progressive and, at present, incurable. A practical and relevant model is needed to investigate the molecular determinants of these debilitating diseases. Mammalian models are often prohibitively expensive, time-consuming and very complex. Given the highly conserved neurological pathways between mammals and invertebrates, Caenorhabditis elegans has emerged as a powerful tool for the investigation of the pathophysiology of these disorders. We describe recent findings in this area and show how C. elegans is being used to broaden our knowledge of human neurodegenerative diseases. PMID- 20298222 TI - Disruption of neuronal function by soluble hyperphosphorylated tau in a Drosophila model of tauopathy. AB - Axonal microtubules are essential for transport of materials to the synapse. Compromised microtubules and synaptic loss have been demonstrated in AD (Alzheimer's disease), which is believed to contribute to cognitive dysfunction before neuronal death in the early stages of the disease. The mechanism by which hyperphosphorylated tau, the building block of neurofibrillary tangles, one of the pathological hallmarks of AD, disrupts neuronal and synaptic function is unclear. There is a theory that hyperphosphorylated tau does not bind effectively to microtubules and is no longer able to function in stabilizing them, thus axonal transport can no longer proceed efficiently. This leads to synaptic dysfunction. We have tested this theory in a Drosophila model of tauopathies in which we expressed human tau (h-tau). Using this model, we have tested all aspects of this hypothesis and have demonstrated that axonal transport does become compromised in the presence of hyperphosphorylated h-tau and this leads to synaptic and behavioural defects. We are currently investigating the mechanism by which hyperphosphorylated h-tau mediates this effect and are preliminary data indicate that this entails phospho-tau-mediated effects that are predicted by the tau-microtubule hypothesis, as well as novel effects. These deleterious effects of h-tau occur in the absence of tau filaments and before neuronal death. This sequence of pathogenic events may constitute the mechanism by which abnormal tau disrupts neuronal and synaptic function and contributes to cognitive impairment before neuronal death in the early stages of tauopathies such as AD. PMID- 20298223 TI - Cell-cell interactions during patterning of the Arabidopsis anther. AB - Key steps in the evolution of the angiosperm anther include the patterning of the concentrically organized microsporangium and the incorporation of four such microsporangia into a leaf-like structure. Mutant studies in the model plant Arabidopsis thaliana are leading to an increasingly accurate picture of (i) the cell lineages culminating in the different cell types present in the microsporangium (the microsporocytes, the tapetum, and the middle and endothecial layers), and (ii) some of the genes responsible for specifying their fates. However, the processes that confer polarity on the developing anther and position the microsporangia within it remain unclear. Certainly, data from a range of experimental strategies suggest that hormones play a central role in establishing polarity and the patterning of the anther initial, and may be responsible for locating the microsporangia. But the fact that microsporangia were originally positioned externally suggests that their development is likely to be autonomous, perhaps with the reproductive cells generating signals controlling the growth and division of the investing anther epidermis. These possibilities are discussed in the context of the expression of genes which initiate and maintain male and female reproductive development, and in the perspective of our current views of anther evolution. PMID- 20298224 TI - Life after meiosis: patterning the angiosperm male gametophyte. AB - Pollen grains represent the highly reduced haploid male gametophyte generation in angiosperms. They play an essential role in plant fertility by generating and delivering twin sperm cells to the embryo sac to undergo double fertilization. The functional specialization of the male gametophyte and double fertilization are considered to be key innovations in the evolutionary success of angiosperms. The haploid nature of the male gametophyte and its highly tractable ontogeny makes it an attractive system to study many fundamental biological processes, such as cell fate determination, cell-cycle progression and gene regulation. The present mini-review encompasses key advances in our understanding of the molecular mechanisms controlling male gametophyte patterning in angiosperms. A brief overview of male gametophyte development is presented, followed by a discussion of the genes required at landmark events of male gametogenesis. The value of the male gametophyte as an experimental system to study the interplay between cell fate determination and cell-cycle progression is also discussed and exemplified with an emerging model outlining the regulatory networks that distinguish the fate of the male germline from its sister vegetative cell. We conclude with a perspective of the impact emerging data will have on future research strategies and how they will develop further our understanding of male gametogenesis and plant development. PMID- 20298225 TI - Inter-cell-layer signalling during Arabidopsis ovule development mediated by the receptor-like kinase STRUBBELIG. AB - Plant organs, such as ovules and flowers, arise through cellular events that are precisely co-ordinated between cells within and across clonally distinct cell layers. Receptor-like kinases are cell-surface receptors that perceive and relay intercellular information. In Arabidopsis the leucine-rich repeat receptor-like kinase STRUBBELIG (SUB) is required for integument initiation and outgrowth during ovule development, floral organ shape and the control of the cell division plane in the first subepidermal cell layer of floral meristems, among other functions. A major goal is to understand SUB-mediated signal transduction at the molecular level. Present evidence suggests that SUB affects neighbouring cells in a non-cell-autonomous fashion. In addition, our results indicate that SUB is an atypical, or kinase-dead, kinase. Forward genetics identified three genes, QUIRKY (QKY), ZERZAUST and DETORQUEO, that are thought to contribute to SUB-dependent signal transduction. QKY encodes a predicted membrane-bound protein with four cytoplasmic C(2) domains. By analogy to animal proteins with related domain topology, we speculate that QKY may be involved in Ca(2+)-dependent signalling and membrane trafficking. Studying SUB-dependent signalling will contribute to our understanding of how atypical kinases mediate signal transduction and how cells co-ordinate their behaviour to allow organs, such as ovules, to develop their three-dimensional architecture. PMID- 20298226 TI - Self-incompatibility in Papaver: identification of the pollen S-determinant PrpS. AB - Many flowering plants are hermaphrodite, posing the problem of self-fertilization and the subsequent loss of the genetic fitness of the offspring. To prevent this, many plants have developed a genetically controlled mechanism called self incompatibility (SI). When the male and female S-determinants match, self (incompatible) pollen is recognized and rejected before fertilization can occur. In poppy (Papaver rhoeas), the pistil S-determinant (PrsS) is a small secreted protein that interacts with incompatible pollen, initiating a Ca(2+)-dependent signalling network. SI triggers several downstream events, including depolymerization of the cytoskeleton, phosphorylation of two soluble inorganic pyrophosphatases and an MAPK (mitogen-activated protein kinase). This culminates in PCD (programmed cell death) involving several caspase-like activities. The recent discovery of the Papaver pollen S-determinant PrpS marks a significant step forward in the understanding of the Papaver SI system. PrpS encodes a ~20 kDa predicted transmembrane protein which has no homology with known proteins. It is specifically expressed in pollen, linked to the pistil S-determinant, and displays the high polymorphism expected of an S-locus determinant. The present review focuses on the discovery and characterization of PrpS which strongly support the hypothesis that Papaver SI is triggered by the interaction of PrsS and PrpS. PMID- 20298227 TI - Functional genomics of pollen tube-pistil interactions in Arabidopsis. AB - The pollen tube represents an attractive model system for functional genomic analysis of the cell-cell interactions that mediate guided cellular growth. The pollen tube extends through pistil tissues and responds to guidance cues that direct the tube towards an ovule, where it releases sperm for fertilization. Pollen is readily isolated from anthers, where it is produced, and can be induced to produce a tube in vitro. Interestingly, pollen tube growth is significantly enhanced in pistils, and pollen tubes are rendered competent to respond to guidance cues after growth in a pistil. This potentiation of the pollen tube by the pistil suggested that pollen tubes alter their gene-expression programme in response to their environment. Recently, the transcriptomes of pollen tubes grown in vitro or through pistil tissues were determined. Significant changes in the transcriptome were found to accompany growth in vitro and through the pistil tissues. Reverse genetic analysis of pollen-tube-induced genes identified a new set of factors critical for pollen tube extension and navigation of the pistil environment. Recent advances reviewed in the present paper suggest that functional genomic analysis of pollen tubes has the potential to uncover the regulatory networks that shape the genetic architecture of the pollen tube as it responds to migratory cues produced by the pistil. PMID- 20298228 TI - Male gamete biology in flowering plants. AB - Flowering plant reproduction is characterized by double fertilization, in which two diminutive brother sperm cells initiate embryo and endosperm. The role of the male gamete, although studied structurally for over a century at various levels, is still being explored on a molecular and cellular level. The potential of the male to influence development has been historically underestimated and the reasons for this are obvious: limitations provided by maternal imprinting, the much greater cellular volume of female gametes and the general paucity of paternal effects. However, as more is known about molecular expression of chromatin-modifying proteins, ubiquitin pathway proteins and transcription factors in sperm cells, as well as their ability to achieve effect by intaglio expression, passing transcripts directly into translation, the role of the male is likely to expand. Much of the expression in the male germline that appears to be distinct from patterns of pollen vegetative cell expression may be the result of chromosomal level regulation of transcription. PMID- 20298229 TI - Reproductive cross-talk: seed development in flowering plants. AB - Flowering plants have evolved to be a predominant life form on earth. A common principle of flowering plants and probably one of the main reasons for their evolutionary success is the rapid development of an embryo next to a supporting tissue called the endosperm. The embryo and the endosperm are protected by surrounding maternal tissues, the integuments, and the trinity of integuments, embryo and endosperm comprise the plant seed. For proper seed development, these three structures have to develop in a highly controlled and co-ordinated manner, representing a paradigm for cell-cell communication during development. Communication pathways between the endosperm and the seed coat are now beginning to be unravelled. Moreover, recently isolated mutants affecting plant reproduction have allowed a genetic dissection of seed development, and revealed that the embryo plays a previously unrecognized yet important role in co ordinating seed development. PMID- 20298230 TI - Floral stem cells: from dynamic balance towards termination. AB - During early flower development in Arabidopsis, floral stem cells proliferate and produce a sufficient amount of cells that are recruited for organogenesis. However, after the central organ primordia initiate, stem cell activity in the floral meristem is terminated to ensure the differentiation of a fixed number of floral organs. Underlying this process, the genetic programme regulating the fate of floral meristems undergoes a shift from a spatially balanced signalling scheme for stem cell maintenance to a temporally controlled transcriptional scheme for stem cell termination. Precise timing of stem cell termination is a key issue for flower development, which is secured by the orchestration of multiple regulators in transcriptional and epigenetic regulation. PMID- 20298231 TI - Through a generation darkly: small RNAs in the gametophyte. AB - The various classes of small non-coding RNAs are a fundamentally important component of the transcriptome. These molecules have roles in many essential processes such as regulation of gene expression at the transcriptional and post transcriptional levels, guidance of DNA methylation and defence against selfish replicators such as transposons. Their diversity and functions in the sporophytic generation of angiosperms is well explored compared with the gametophytic generation, where little is known about them. Recent progress in understanding their abundance, diversity and function in the gametophyte is reviewed. PMID- 20298232 TI - Protein interactions and subcellular localization in S-RNase-based self incompatibility. AB - The recent identification of several proteins playing key roles in S-RNase-based gametophytic self-incompatibility has led both to a greater understanding of the molecular biology of this response, as well as to questions regarding the precise mechanism by which compatible pollen tubes are recognized and accepted. A proposed variant SCF(SLF) (where SCF is SSK1/cullin/F-box and SLF is S-locus F box) ubiquitin ligase complex is thought to play a central role in recognizing and inhibiting non-self S-RNases, but the exact role of ubiquitination remains unclear. How the possible sequestration of non-self S-RNases in a pollen vacuolar compartment can be reconciled with the need for protein interaction between S RNase and the SCF(SLF) complex needs to be determined. Current work to answer these questions focuses on more precisely defining quantitative protein interactions and subcellular localization of proteins involved in S-RNase-based gametophytic self-incompatibility. PMID- 20298233 TI - Female gametophyte-controlled pollen tube guidance. AB - During the evolution of flowering plants, their sperm cells have lost mobility and are transported from the stigma to the female gametophyte via the pollen tube to achieve double fertilization. Pollen tube growth and guidance is largely governed by the maternal sporophytic tissues of the stigma, style and ovule. However, the last phase of the pollen tube path is under female gametophyte control and is expected to require extensive cell-cell communication events between both gametophytes. Until recently, little was known about the molecules produced by the female gametophyte that are involved in this process. In the present paper, we review the most recent development in this field and focus on the role of secreted candidate signalling ligands. PMID- 20298234 TI - Sporophytic control of pollen tube growth and guidance in grasses. AB - Pollen tube growth and guidance in the female tissues of flowering plants is a long-studied and anatomically well-described process. A large number of gene products and chemical compounds involved have been identified in the last 20 years, and some underlying molecular mechanisms including self-incompatibility in the Brassicaceae, Solanaceae and Papaveraceae are now well understood. However, the largest part of the pollen tube pathway inside the transmitting tract towards the ovule harbouring the female gametophyte still requires intensive investigations. Especially in the economically most import plant family, the Poaceae or grasses, progamic pollen tube development is barely understood. Using maize as a model, we propose to divide pollen tube germination, growth and guidance towards the female gametophyte into five distinct phases. The model is adapted from Arabidopsis thaliana, taking anatomical differences and novel genetic and cellular studies into consideration. With the exception of Phase V, all phases seem to be under sporophytic control in grasses. PMID- 20298235 TI - Let's get physical: gamete interaction in flowering plants. AB - Fertilization comprises a series of precisely orchestrated steps that culminate in the fusion of male and female gametes. The most intimate steps during fertilization encompass gamete recognition, adhesion and fusion. In animals, some binding-effector proteins and enzymes have been identified that act on the cell surfaces of the gametes to regulate gamete compatibility and fertilization success. In contrast, exploring plant gamete interaction during double fertilization, a characteristic trait of flowering plants, has been hampered for a long time because of the protected location of the female gametes and technical limitations. Over the last couple of years, however, the use of advanced methodologies, new imaging tools and new mutants has provided deeper insights into double fertilization, at both the cellular and the molecular level, especially for the model plant Arabidopsis thaliana. Most likely, one consequence of inventing double fertilization may be the co-evolution of special molecular mechanisms to govern each successful sperm delivery and efficient gamete recognition and fusion. In vivo imaging of double fertilization and the recent discovery of numerous female-gametophyte-specific expressed genes encoding small secreted proteins, some of whom were found to be essential for the fertilization process, support this hypothesis. Nevertheless, recent findings indicate that at least the membrane-merger step in plant gamete interaction may rely on an ancient and widely used gamete fusion system. PMID- 20298236 TI - Recent achievements and trends in experimental plant biology. AB - Between 21 and 25 September 2009, Krakow hosted the 4th Conference of the Polish Society of Experimental Plant Biology, co-organized with the Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Krakow, and supported by the Biochemical Society. The aim of the conference was to present and discuss the most important topics in different disciplines of plant experimental science as well as to facilitate the interaction and co-operation between scientists. To achieve this goal, about 30 top specialists in various areas of plant biology were invited to give plenary lectures in the following sessions: Plant structure and development; Plant-microbial interactions; Mitochondria and chloroplasts in cell metabolism; Stress tolerance in plants; Structural and functional organization of plant genomes; Mutants in developmental and metabolic studies; Secondary metabolites as pharmaceutics and nutraceutics; Plant membranes; and Integrating plant functions via signalling molecules: molecular mechanisms. Some of the main problems highlighted in the plenary lectures are briefly summarized in the present paper. Two poster sessions enabled a discussion of over 200 posters presented. The conference had an international character, its official language was English, and among the more than 350 participants, about 60 were from abroad. Several plenary lectures were prepared as short review papers and they are published in this issue of Biochemical Society Transactions. PMID- 20298237 TI - The role of chemical dynamics in plant morphogenesis(1). AB - In biological development, the generation of shape is preceded by the spatial localization of growth factors. Localization, and how it is maintained or changed during the process of growth, determines the shapes produced. Mathematical models have been developed to investigate the chemical, mechanical and transport properties involved in plant morphogenesis. These synthesize biochemical and biophysical data, revealing underlying principles, especially the importance of dynamics in generating form. Chemical kinetics has been used to understand the constraints on reaction and transport rates to produce localized concentration patterns. This approach is well developed for understanding de novo pattern formation, pattern spacing and transitions from one pattern to another. For plants, growth is continual, and a key use of the theory is in understanding the feedback between patterning and growth, especially for morphogenetic events which break symmetry, such as tip branching. Within the context of morphogenetic modelling in general, the present review gives a brief history of chemical patterning research and its particular application to shape generation in plant development. PMID- 20298238 TI - Regulation of plant light harvesting by thermal dissipation of excess energy. AB - Elucidating the molecular details of qE (energy quenching) induction in higher plants has proven to be a major challenge. Identification of qE mutants has provided initial information on functional elements involved in the qE mechanism; furthermore, investigations on isolated pigment-protein complexes and analysis in vivo and in vitro by sophisticated spectroscopic methods have been used for the elucidation of mechanisms involved. The aim of the present review is to summarize the current knowledge of the phenotype of npq (non-photochemical quenching) knockout mutants, the role of gene products involved in the qE process and compare the molecular models proposed for this process. PMID- 20298239 TI - Involvement of mitochondria in the control of plant cell NAD(P)H reduction levels. AB - NADPH and NADH mediate reductant flow between cellular processes, linking central carbon and energy metabolism with intermediary metabolism, stress defence and development. Recent investigations have revealed paths of functional interactions, and have suggested that mitochondrial NADPH oxidation, especially together with the oxidative pentose phosphate pathway, is an important regulator of the cytosolic NADPH reduction level. Furthermore, stress-dependent metabolic pathways substantially affect the NADPH reduction level in particular physiological situations. The mitochondrial impact on the NADPH reduction level provides a model example of the physiological significance of the mitochondrial NAD(P)H dehydrogenase set-up, which is more complex in plants than in other organisms. PMID- 20298240 TI - Regulation of plant gene expression by alternative splicing. AB - AS (alternative splicing) is a post-transcriptional process which regulates gene expression through increasing protein complexity and modulating mRNA transcript levels. Regulation of AS depends on interactions between trans-acting protein factors and cis-acting signals in the pre-mRNA (precursor mRNA) transcripts, termed 'combinatorial' control. Dynamic changes in AS patterns reflect changes in abundance, composition and activity of splicing factors in different cell types and in response to cellular or environmental cues. Whereas the SR protein family of splicing factors is well-studied in plants, relatively little is known about other factors influencing the regulation of AS or the consequences of AS on mRNA levels and protein function. To address fundamental questions on AS in plants, we are exploiting a high-resolution RT (reverse transcription)-PCR system to analyse multiple AS events simultaneously. In the present paper, we describe the current applications and development of the AS RT-PCR panel in investigating the roles of splicing factors, cap-binding proteins and nonsense-mediated decay proteins on AS, and examining the extent of AS in genes involved in the same developmental pathway or process. PMID- 20298242 TI - Recent developments in photorespiration research. AB - Photorespiration is the light-dependent release of CO(2) initiated by Rubisco (ribulose-1,5-bisphosphate carboxylase/oxygenase) during oxygenic photosynthesis. It occurs during the biochemical reactions of the photorespiratory C(2) cycle, which is an ancillary metabolic process that allows photosynthesis to occur in oxygen-containing environments. Recent research has identified the genes for many plant photorespiratory enzymes, allowing precise functional analyses by reverse genetics. Similar studies with cyanobacteria disclosed the evolutionary origin of photorespiratory metabolism in these ancestors of plastids. PMID- 20298241 TI - Nucleolar RNPs: from genes to functional snoRNAs in plants. AB - The snoRNAs (small nucleolar RNAs) and related scaRNAs (small RNAs in the Cajal bodies) represent a major class of nuclear RNAs that guide 2'-O-ribose methylation and pseudouridylation of rRNAs, snRNAs (small nuclear RNAs) and other RNA targets. In vivo, all snoRNAs associate with a set of four highly conserved nucleolar proteins, forming the functional snoRNPs (small nucleolar ribonucleoproteins). The core structure of these mature snoRNPs has now been well described in eukaryotes, but less is known of their biogenesis. Recent data in animals and yeast reveal that assembly of the snoRNPs is a complex process that implicates several auxiliary proteins and transient protein-protein interactions. This new level of snoRNP regulation is now beginning to be unravelled in animals and yeast, but remains unexplored in plants. In the present paper, we review recent data from genomic and functional analysis allowing the identification and study of factors controlling the biogenesis of plant snoRNPs and their impact on plant development. PMID- 20298243 TI - Exploiting induced variation to dissect quantitative traits in barley. AB - The identification of genes underlying complex quantitative traits such as grain yield by means of conventional genetic analysis (positional cloning) requires the development of several large mapping populations. However, it is possible that phenotypically related, but more extreme, allelic variants generated by mutational studies could provide a means for more efficient cloning of QTLs (quantitative trait loci). In barley (Hordeum vulgare), with the development of high-throughput genome analysis tools, efficient genome-wide identification of genetic loci harbouring mutant alleles has recently become possible. Genotypic data from NILs (near-isogenic lines) that carry induced or natural variants of genes that control aspects of plant development can be compared with the location of QTLs to potentially identify candidate genes for development--related traits such as grain yield. As yield itself can be divided into a number of allometric component traits such as tillers per plant, kernels per spike and kernel size, mutant alleles that both affect these traits and are located within the confidence intervals for major yield QTLs may represent extreme variants of the underlying genes. In addition, the development of detailed comparative genomic models based on the alignment of a high-density barley gene map with the rice and sorghum physical maps, has enabled an informed prioritization of 'known function' genes as candidates for both QTLs and induced mutant genes. PMID- 20298244 TI - Mutations in genes controlling the biosynthesis and accumulation of inositol phosphates in seeds. AB - Most of the phosphorus in the resting seed is stored inside protein storage vacuoles as PA (phytic acid; InsP(6)). The biosynthesis and accumulation of PA can be detected beginning from a few days after anthesis and seem to continue during seed development until maturation. The first step in PA biosynthesis is the formation of Ins3P by conversion of glucose 6-phosphate. This is then followed by a sequential and ordered phosphorylation of the remaining five positions of the inositol ring by a number of kinases, resulting in PA. Identification of low-PA mutants in cereals, legumes and Arabidopsis is instrumental for resolving the biosynthetic pathway and identification of genes controlling the accumulation of PA. Mutations in seven genes involved in the metabolism of PA have been identified and characterized among five plant species using induced mutagenesis and insertion elements. Understanding the biosynthetic pathway and genes controlling the accumulation of PA in plant seeds and how PA may balance the free phosphate is of importance for molecular breeding of crop plants, particularly cereals and legumes. PMID- 20298245 TI - Genistein: a natural isoflavone with a potential for treatment of genetic diseases. AB - Genistein [4',5,7-trihydroxyisoflavone or 5,7-dihydroxy-3-(4-hydroxyphenyl)-4H-1 benzopyran-4-one] is a natural isoflavone occurring in many plants known to possess various biological activities, ranging from phyto-oestrogenic to antioxidative actions. Recent studies indicated that this isoflavone can also be considered as a drug for as yet untreatable genetic diseases. In the present review, we discuss a plausible use of genistein in treatment of two genetic disorders: CF (cystic fibrosis) and MPS (mucopolysaccharidosis). Although various biological actions of genistein are employed in these two cases, in vitro studies, tests on animal models and pilot clinical trials suggest that this plant derived compound might be a real hope for patients suffering from severe inherited disorders with relatively complicated pathomechanisms, including those affecting the central nervous system. PMID- 20298246 TI - Light-driven regulatory mechanisms in the photosynthetic antenna complex LHCII. AB - Protection against strong-light-induced photodamage of the photosynthetic apparatus and entire organisms is a vital activity in plants and is also realized at the molecular level of the antenna complexes. Reported recently, the regulatory mechanisms which operate in the largest plant antenna complex, LHCII (light-harvesting complex II), based on light-driven processes, are briefly reviewed and discussed. Among those processes are the light-induced twisting of the configuration of the LHCII-bound neoxanthin, the light-induced configurational transition of the LHCII-bound violaxanthin, the light-induced trimer-monomer transition in LHCII and the blue-light-induced excitation quenching in LHCII. The physiological importance of the processes reviewed is also discussed with emphasis on the photoprotective excitation quenching and on possible involvement in the regulation of the xanthophyll cycle. PMID- 20298247 TI - Phosphatidylinositol 4,5-bisphosphate regulates plant K(+) channels. AB - Phosphoinositides play an important role in both abiotic and biotic signalling in plants. The signalling cascade may include the production of second messengers by hydrolysis of PtdIns(4,5)P(2). However, increasingly, PtdIns(4,5)P(2) itself is shown to mediate signalling by regulating target proteins. The present mini review summarizes the experimentally demonstrated effects of PtdIns(4,5)P(2) on plant K(+) channels and examines their structure for candidate sites of direct PtdIns(4,5)P(2)-protein interaction. PMID- 20298248 TI - Phytochrome three-dimensional structures and functions. AB - The complete three-dimensional sensory module structures of the Pr ground state of Synechocystis 6803 Cph1 and the unusual Pfr ground state of the bacteriophytochrome PaBphP (PDB codes 2VEA and 3C2W respectively) have now been solved, revealing an asymmetrical dumbbell form made up of a PAS (Period/ARNT/Singleminded)-GAF (cGMP phosphodiesterase/adenylate cyclase/FhlA) bidomain carrying the chromophore and the smaller PHY (phytochrome-specific) domain. The PHY domain is structurally related to the GAF family, but carries an unusual tongue-like structure which contacts the larger lobe to seal the chromophore pocket. In 2VEA, the tongue makes intimate contact with the helical N terminus; both the N-terminus and the tongue structures are quite different in 3C2W. As expected, the structures reveal ZZZssa and ZZEssa chromophore conformations in 2VEA and 3C2W respectively, associated with tautomeric differences in several nearby tyrosine residues. Two salt bridges on opposite sides of the chromophore, as well as the associations of the C-ring propionates also differ. It is still unclear, however, which of these structural differences are associated with bacteriophytochromes compared with Cph1 and plant-type phytochromes, the unusual 3C2W Pfr ground state functionality compared with the Pr ground state or the Pr compared with Pfr photoisomerism. To access the latter unambiguously, both Pr and Pfr structures of the same molecule are required. New solid-phase NMR data for Cph1 in the Pr, Pfr and freeze-trapped intermediate states reveal unexpected changes in the chromophore during Pfr-->Pr photoconversion. These, together with our efforts to solve the three-dimensional structure of a complete phytochrome molecule are also described. PMID- 20298249 TI - Auxin and strigolactones in shoot branching: intimately connected? AB - Axillary meristems form in the axils of leaves. After an initial phase of meristematic activity during which a small axillary bud is produced, they often enter a state of suspended growth from which they may be released to form a shoot branch. This post-embryonic growth plasticity is typical of plants and allows them to adapt to changing environmental conditions. The shoot architecture of genotypically identical plants may display completely contrasting phenotypes when grown in distinct environmental niches, with one having only a primary inflorescence and many arrested axillary meristems and the other displaying higher orders of branches. In order to cease and resume growth as required, the plant must co-ordinate its intrinsic developmental programme with the responses to environmental cues. It is thought that information from the environment is integrated throughout the plant using plant hormones as long-distance signals. In the present review, we focus primarily on how two of these hormones, auxin and strigolactones, may be acting to regulate shoot branching. PMID- 20298250 TI - Recycling domains in plant cell morphogenesis: small GTPase effectors, plasma membrane signalling and the exocyst. AB - The Rho/Rop small GTPase regulatory module is central for initiating exocytotically ACDs (active cortical domains) in plant cell cortex, and a growing array of Rop regulators and effectors are being discovered in plants. Structural membrane phospholipids are important constituents of cells as well as signals, and phospholipid-modifying enzymes are well known effectors of small GTPases. We have shown that PLDs (phospholipases D) and their product, PA (phosphatidic acid), belong to the regulators of the secretory pathway in plants. We have also shown that specific NOXs (NADPH oxidases) producing ROS (reactive oxygen species) are involved in cell growth as exemplified by pollen tubes and root hairs. Most plant cells exhibit several distinct plasma membrane domains (ACDs), established and maintained by endocytosis/exocytosis-driven membrane protein recycling. We proposed recently the concept of a 'recycling domain' (RD), uniting the ACD and the connected endosomal recycling compartment (endosome), as a dynamic spatiotemporal entity. We have described a putative GTPase-effector complex exocyst involved in exocytic vesicle tethering in plants. Owing to the multiplicity of its Exo70 subunits, this complex, along with many RabA GTPases (putative recycling endosome organizers), may belong to core regulators of RD organization in plants. PMID- 20298251 TI - Development of romiplostim for the treatment of patients with chronic immune thrombocytopenia: from bench to bedside. AB - Immune thrombocytopenia (ITP) is an autoimmune disorder characterised by abnormally low platelet counts (<100 x 10(9)/l), purpura, and bleeding episodes, and can be categorised in three phases: newly-diagnosed, persistent, and chronic. As many patients become refractory to standard treatments (corticosteroids, danazol, azathioprine, splenectomy), there is an urgent need for alternative treatments. The successful isolation and cloning of thrombopoietin (TPO) in the mid-1990s and identification of its key role in platelet production was a major breakthrough, rapidly followed by the development of the recombinant thrombopoietins, recombinant human TPO and a pegylated truncated product, PEG rHuMGDF. Both agents increased platelet counts but development was halted because of the development of antibodies that cross-reacted with native TPO, resulting in prolonged treatment-refractory thrombocytopenia. Experimentation with novel platforms for extending the circulating half-life of therapeutic peptides by combining them with antibody fragment crystallisable (Fc) constructs led to the development of a new family of molecules termed 'peptibodies'. The 60Da recombinant peptibody romiplostim was finally produced by linking several copies of an active TPO-binding peptide sequence to a carrier Fc fragment. In clinical trials, romiplostim was effective in ameliorating thrombocytopenia in patients with chronic ITP, was well tolerated and did not elicit cross-reacting antibodies. Romiplostim has recently been approved for the treatment of adults with chronic ITP. PMID- 20298252 TI - Diagnostic performance of computer tomography, magnetic resonance imaging, and positron emission tomography or positron emission tomography/computer tomography for detection of metastatic lymph nodes in patients with cervical cancer: meta analysis. AB - We performed a meta-analysis to compare diagnostic performances of computed tomography (CT), magnetic resonance imaging (MRI), and positron emission tomography (PET or PET/CT), for detection of metastatic lymph nodes in patients with cervical cancer. We searched MEDLINE (PubMed), EMBASE and the Cochrane Review database in December 2007. All articles were independently reviewed and selected by three evaluators. We estimated a summary receiver operating characteristic (sROC) curve. The area under the curve (AUC), Q*, and pooled weighted estimates of sensitivity and specificity for each modality by patient based and region- or node-based data analyses and conducted pair-wise comparisons between modalities using the two-sample Z-test. Forty-one of 768 initially identified studies were included in the meta-analysis. In a patient-based data analysis, PET or PET/CT showed the highest pooled sensitivity (82%) and specificity (95%), while CT showed 50% and 92%; and MRI, 56% and 91%, respectively. The AUC (0.9641) and Q* (0.9106) of PET or PET/CT were significantly higher than those of MRI (AUC = 0.8270; Q* = 0.7599), both P < 0.001. In region- or node-based data analysis, sensitivities of CT (52%) and PET or PET/CT (54%) were higher than that of MRI (38%), P < 0.02 and P < 0.001, respectively, while specificities of MRI (97%) and PET or PET/CT (97%) were higher than that of CT (92%), both P < 0.001. The AUC and Q* showed no significant difference among CT, MRI, and PET or PET/CT. PET or PET/CT had an overall higher diagnostic performance than did CT or MRI in detecting metastatic lymph nodes in patients with cervical cancer. PMID- 20298253 TI - Skin tightening effect using fractional laser treatment II: A pilot animal study on skin remodeling. AB - BACKGROUND: Fractional laser resurfacing is a new procedure for skin rejuvenation. We have found that it has a skin tightening effect in humans. OBJECTIVE: To assess the mechanism of the skin tightening effect of fractional laser treatment in animals using histologic approaches. METHODS: The dorsal skin of hairless guinea pigs was irradiated with a fractional 1,540-nm erbium glass laser. Biopsy specimens were taken serially from 0 hour until 1 year after irradiation and evaluated histologically. RESULTS: Histologic evaluation indicated dermal remodeling within 2 months, in which regenerated collagen bundles and fibroblasts aligned in a horizontal direction, suggesting a traction stress on the dermal components. The treated part became less obvious over a period of more than 3 months by recovery of fine collagen bundles without fibrosis. CONCLUSION: These results suggest that improvement of the tension in a horizontal direction is essential for skin remodeling and improvement of facial laxity using fractional laser resurfacing. PMID- 20298254 TI - Low-fluence Q-switched neodymium-doped yttrium aluminum garnet (1,064 nm) laser for the treatment of facial melasma in Asians. AB - BACKGROUND: Pigment lasers have been used in melasma with unsatisfactory results. OBJECTIVE: To determine the effectiveness and safety of 1,064-nm Q-switched neodymium-doped yttrium aluminum garnet (QS-Nd:YAG) laser treatment of melasma in Asians. MATERIALS AND METHODS: Split-face randomized study comparing combination QS-Nd:YAG laser and 2% hydroquinone with topical treatment in dermal or mixed type melasma. Twenty-two patients were treated with 1,064-nm QS-Nd:YAG laser, 6 mm spot size, 3.0- to 3.8-J/cm(2) fluence for five sessions at 1-week intervals. Pigmentation was objectively recorded using a colorimeter (lightness index score), and subjective assessments were evaluated using the modified Melasma Area and Severity Index (mMASI) score. RESULTS: After five laser treatments, statistically significant improvement of melasma from baseline was observed in colorimeter (p<.001) and mMASI score (p<.001) on the laser side. The laser side achieved an average 92.5% improvement in relative lightness index and 75.9% improvement in mMASI, compared with 19.7% and 24%, respectively, on the control side (p<.001). Mottled hypopigmentation developed in three patients. During follow-up, four of 22 patients developed rebound hyperpigmentation, and all patients had recurrence of melasma. CONCLUSION: QS-Nd:YAG laser treatment for melasma in Asians produced only temporary improvement and had side effects. Common complications were hypopigmentation, melasma recurrence, and rebound hyperpigmentation. PMID- 20298255 TI - Letter: an alternative technique to repair large loss of substance of the scalp. PMID- 20298257 TI - Preimplantation development of mouse: a view from cellular behavior. AB - A mature animal body contains a variety of different cell types, and these cells are distributed in a well-organized fashion along the body axes. One of the major questions in developmental biology is how cells acquire different characteristics. In addition, it is important to understand how the embryo forms the body axes and how cells are allocated along these axes during development. Among mammalian species, the molecular mechanisms that regulate embryonic development have been well analyzed and characterized in mice. Here, mouse preimplantation embryonic development is briefly summarized and our current understanding of this complex process based on recent observations is reviewed. PMID- 20298258 TI - Epiblast stem cells contribute new insight into pluripotency and gastrulation. AB - Gastrulation is the defining feature of metazoan development where it serves to apportion seemingly equivalent, pluripotent cells to specific fates. The three embryonic germ layers generated during gastrulation from the pluripotent epiblast including ectoderm, mesoderm, and definitive endoderm, contain the progenitors required to build all of the tissues of the developing organism. As a result, there is great interest in understanding the events that coordinate gastrulation. Because developing embryos in placental mammals are relatively inaccessible, stem cells are widely used for experimental and biochemical interrogation of these processes. Epiblast stem cells (EpiSCs) are grown from the post-implantation epiblast, which is the most proximal pluripotent tissue to the early somatic and germ cell precursors. Because EpiSCs can be propagated indefinitely in vitro as a stable state that recapitulates the properties of the post-implantation epiblast, they are uniquely positioned to provide novel insight into the developmental window where somatic and germ cell lineages are first established. Here we discuss the nature of EpiSCs and their significance in understanding gastrulation and cell specification in relationship to other pluripotent cell culture models. PMID- 20298259 TI - Coordinated regulation of dorsal bone morphogenetic protein 4 and ventral Sonic hedgehog signaling specifies the dorso-ventral polarity in the optic vesicle and governs ocular morphogenesis through fibroblast growth factor 8 upregulation. AB - Dorsal and ventral specification in the early optic vesicle plays a crucial role in vertebrate ocular morphogenesis, and proper dorsal-ventral polarity in the optic vesicle ensures that distinct structures develop in separate domains within the eye primordium. The polarity is determined progressively during development by coordinated regulation of extraocular dorsal and ventral factors. In the present study, we cultured discrete portions of embryonic chick brains by preparing anterior cephalon, anterior dorsal cephalon and anterior ventral cephalon, and clearly demonstrate that bone morphogenetic protein 4 (BMP4) and Sonic hedgehog (Shh) constitute a dorsal-ventral signaling system together with fibroblast growth factor 8 (FGF8). BMP4 and Shh upregulate Tbx5 and Pax2, as reported previously, and at the same time Shh downregulates Tbx5, while BMP4 affects Pax2 expression to downregulate similarly. Shh induces Fgf8 expression in the ventral optic vesicle. This, in turn, determines the distinct boundary of the retinal pigmented epithelium and the neural retina by suppressing Mitf expression. The lens develops only when signals from both the dorsal and ventral regions come across together. Inverted deposition of Shh and BMP4 signals in organ-cultured optic vesicle completely re-organized ocular structures to be inverted. Based on these observations we propose a novel model in which the two signals govern the whole of ocular development when they encounter each other in the ocular morphogenic domain. PMID- 20298260 TI - Direct reprogramming 101. AB - Direct reprogramming of somatic cells into a pluripotent state has been achieved with a set of just four transcription factors. Many scientists and medical doctors are trying to elucidate the causes of intractable diseases and discover new drugs using the newest types of technology. Various methods have been developed to produce clinical-grade fully reprogrammed cells for cell transplantation therapy. Augmenting agents, such as small-molecules, have been extensively screened to improve the reprogramming efficiency. The molecular mechanisms of reprogramming have been revealed by embryonic stem cell research. The accumulation of knowledge by the pioneers has driven the reprogramming field. In the present article, the contents of gift boxes from the studies of pluripotency to the nuclear reprogramming field are introduced. PMID- 20298261 TI - Vulnerability of schools to floods in Nyando River catchment, Kenya. AB - This paper assesses the vulnerability of schools to floods in the Nyando River catchment (3,600 km(2)) in western Kenya and identifies measures needed to reduce this vulnerability. It surveys 130 schools in the lower reaches, where flooding is a recurrent phenomenon. Of the primary schools assessed, 40% were vulnerable, 48% were marginally vulnerable and 12% were not vulnerable. Of the secondary schools, 8% were vulnerable, 73% were marginally vulnerable and 19% were not vulnerable. Vulnerability to floods is due to a lack of funds, poor building standards, local topography, soil types and inadequate drainage. The Constituencies Development Fund (CDF), established in 2003, provides financial support to cover school construction and reconstruction costs; CDF Committees are expected to adopt school building standards. In an effort to promote safe and resilient construction and retrofitting to withstand floods, this paper presents vulnerability reduction strategies and recommendations for incorporating minimum standards in the on-going Primary School Infrastructure Programme Design. PMID- 20298262 TI - Assessing the impact of the Indian Ocean tsunami on households: a modified domestic assets index approach. AB - This paper offers a potential measurement solution for assessing disaster impacts and subsequent recovery at the household level by using a modified domestic assets index (MDAI) approach. Assessment of the utility of the domestic assets index first proposed by Bates, Killian and Peacock (1984) has been confined to earthquake areas in the Americas and southern Europe. This paper modifies and extends the approach to the Indian sub-continent and to coastal surge hazards utilizing data collected from 1,000 households impacted by the Indian Ocean tsunami (2004) in the Nagapattinam district of south-eastern India. The analyses suggest that the MDAI scale is a reliable and valid measure of household living conditions and is useful in assessing disaster impacts and tracking recovery efforts over time. It can facilitate longitudinal studies, encourage cross cultural, cross-national comparisons of disaster impacts and inform national and international donors of the itemized monetary losses from disasters at the household level. PMID- 20298263 TI - Proposal for a quantitative index of flood disasters. AB - Drawing on calculations of wind scale and earthquake magnitude, this paper develops a new quantitative method for measuring flood magnitude and disaster intensity. Flood magnitude is the quantitative index that describes the scale of a flood; the flood's disaster intensity is the quantitative index describing the losses caused. Both indices have numerous theoretical and practical advantages with definable concepts and simple applications, which lend them key practical significance. PMID- 20298264 TI - Post-earthquake rehabilitation of the rural water systems in Kashmir's Jehlum Valley. AB - After the devastating earthquake of 8 October 2005 in Kashmir, international organizations provided the Pakistani government with relief and reconstruction assistance. Under the oft-cited motto 'rebuild better', many of these efforts targeted the rural areas. The emergency period was followed by a development phase, during which all actors sought to ensure that their reconstruction projects would have long-term, sustainable impacts. Based on the authors' experience during that phase, this paper offers specific guidelines for rehabilitation work on Kashmir's rural water supply system, stressing the need for analysis of the social context to guarantee sustainability of the completed projects. PMID- 20298265 TI - Fiji's worst natural disaster: the 1931 hurricane and flood. AB - At least 225 people in the Fiji Islands died as a result of the 1931 hurricane and flood, representing the largest loss of life from a natural disaster in Fiji's recent history. This paper explores the causes of disaster and the potential for recurrence. The disaster occurred because a rare event surprised hundreds of people-especially recently settled Indian farmers-occupying highly exposed floodplains in north-west Viti Levu island. The likelihood of a flood disaster of such proportions occurring today has been diminished by changed settlement patterns and building materials; however, a trend towards re-occupancy of floodplains, sometimes in fragile dwellings, is exposing new generations to flood risks. The contribution of this paper to the global hazards literature is set out in three sections: the ethnicity, gender and age of flood fatalities; the naturalness of disasters; and the merit of choice and constraint as explanations for patterns of vulnerability. PMID- 20298266 TI - Transformative experiences for Hurricanes Katrina and Rita disaster volunteers. AB - The massive destruction caused by Hurricanes Katrina and Rita in 2005 provided an opportunity for many volunteers to be involved with disaster relief work. Exposure to devastation and personal trauma can have long-lasting and sometimes detrimental effects on people providing help. This qualitative study explored the experience of volunteer relief workers who provided disaster relief services after the hurricanes. Three major themes emerged: emotional reactions that included feelings of shock, fatigue, anger and grief as well as sleep disturbances; frustration with leadership; and life-changing personal transformation. Stress reactions were noted but appeared to be mitigated by feelings of compassion for the victims and personal satisfaction in being able to provide assistance. Suggestions are provided for further research. PMID- 20298267 TI - Epidemiology of methicillin-resistant Staphylococcus aureus lineages in five major African towns: emergence and spread of atypical clones. AB - The epidemiology of methicillin-resistant Staphylococcus aureus (MRSA) in Africa is poorly documented. From January 2007 to March 2008, we collected 86 MRSA isolates from five African towns, one each in Cameroon, Madagascar, Morocco, Niger and Senegal. Although one or two major clones, defined by the sequence type and staphylococcal cassette chromosome mec type, predominated at each site, genetic diversity (ten clones) was relatively limited in view of the large geographical area studied. Most of the isolates (n = 76, 88%) belonged to three major clones, namely ST239/241-III, a well-known pandemic clone (n = 34, 40%), ST88-IV (n = 24, 28%) and ST5-IV (n = 18, 21%). The latter two clones have only been sporadically described in other parts of the world. The spread of community associated MRSA carrying the Panton-Valentine leukocidin genes is a cause for concern, especially in Dakar and possibly throughout Africa. PMID- 20298268 TI - Multiplex real-time PCR for the diagnosis of malaria: correlation with microscopy. AB - Malaria is generally diagnosed by microscopy and rapid antigen testing. Molecular methods become more widely used. In the present study, the contribution of a quantitative multiplex malaria PCR was investigated. We assessed: (i) the agreement between PCR-based identification and microscopy and (ii) the correlation between the parasite load as determined by quantitative PCR and by microscopy. For 83 patients positive by microscopy for Plasmodium spp., the first EDTA-blood sample was tested by multiplex PCR to confirm smear-based species identification. Parasite load was assessed daily using both microscopy and PCR. Among the 83 patients tested, one was positive by microscopy only and 82 were positive by microscopy and PCR. Agreement between microscopy and PCR for the identification at the species level was 89% (73/82). Six of the nine discordant results corresponded to co-infections by two or three species and were attributed to inaccurate morphological identification of mixed cases. The parasite load generally decreased rapidly after treatment had been started, with similar decay curves being obtained using both microscopy and PCR. Our PCR proved especially useful for identifying mixed infections. The quantification obtained by PCR closely correlated with microscopy-based quantification and could be useful for monitoring treatment efficacy, at least in clinical trials. PMID- 20298269 TI - Development of a real-time PCR targeting the yidC gene for the detection of Mycoplasma hominis and comparison with quantitative culture. AB - Mycoplasma hominis is an opportunistic human mycoplasma species that can be either commensal or pathogenic. Its detection by culture is considered to comprise the reference technique. Previously reported PCR techniques target the 16S rRNA or the gap gene, although sequence variations among clinical isolates may lead to variations in clinical sensitivity. The present study aimed to develop a specific TaqMan quantitative real-time PCR assay, targeting a gene conserved in all M. hominis isolates, and to compare it with quantitative culture. With the knowledge of the M. hominis PG21 genome sequence, the yidC gene, encoding a membrane protein translocase, was chosen as target. Its intraspecies heterogeneity was checked at the nucleotide level using 31 reference or clinical strains. The limit of detection, the analytical specificity and the reproducibility of the assay were assessed. Moreover, PCR and culture results were compared using 153 urogenital specimens. The limit of detection was seven copies/MUL. The analytical specificity was 100%, with good inter- and intra-assay reproducibility. Among the 153 urogenital specimens, the yidC PCR and culture allowed detection of 55 and 45 M. hominis-positive samples, respectively. Comparison of the bacterial load among the 45 specimens found to be M. hominis positive by both techniques revealed a statistically significant association between the quantitative results obtained. In conclusion, we developed a specific, sensitive and reproducible real-time PCR to detect all M. hominis clinical isolates. This PCR was shown to have higher sensitivity than culture, although both methods were correlated for quantification of M. hominis loads in urogenital specimens. PMID- 20298270 TI - Loop-mediated isothermal amplification assay for the diagnosis of retinitis caused by herpes simplex virus-1. AB - A loop-mediated isothermal amplification (LAMP) assay was developed for the detection of herpes simplex virus 1 (HSV-1). The specificity of the assay was tested using DNA extracted from HSV-1-infected rabbit corneal epithelium cultures, HSV-2 grown on Vero cell line, cytomegalovirus (CMV) (AD-169), varicella zoster virus (VZV) (Oka-vaccine), adenovirus, Aspergillus flavus and Staphylococcus aureus. The specificity of LAMP was confirmed by bidirectional sequencing of the amplicons. The sensitivity of the LAMP assay was tested using different concentrations of HSV-1 DNA. To evaluate the application of the LAMP assay in clinical diagnosis, we tested vitreous samples from 20 patients with suspected viral retinitis using LAMP and real-time PCR for HSV-1. The LAMP primers amplified only HSV-1 DNA; no LAMP products were detected with the DNAs of HSV-2, CMV, VZV, adenovirus A. flavus and S. aureus. The sequences of the positive HSV-1 LAMP products perfectly (99-100%) matched the HSV-1 sequences deposited in the GenBank database. LAMP is as sensitive as real-time PCR, with the lowest detection limit being 10 copies/MUL of HSV-1 DNA. Of the 20 patients with suspected viral retinitis, four tested positive for HSV-1 using real- time PCR and LAMP. A 100% concordance was observed across the two methods. The LAMP assay is a rapid, highly specific and sensitive method for the diagnosis of retinitis caused by HSV-1. PMID- 20298272 TI - Monitoring asthma therapy using indirect bronchial provocation tests. AB - OBJECTIVES: Bronchial provocation tests that assess airway hyperresponsiveness (AHR) are known to be useful in assisting the diagnosis of asthma and in monitoring inhaled corticosteroid therapy. We reviewed the use of bronchial provocation tests that use stimuli that act indirectly for monitoring the benefits of inhaled corticosteroids. DATA SOURCE: Published clinical trials investigating the effect of inhaled corticosteroids on bronchial hyperresponsiveness in persons with asthma were used for this review. STUDY SELECTION: Studies using indirect stimuli to provoke airway narrowing such as exercise, eucapnic voluntary hyperventilation, cold air hyperventilation, hypertonic saline, mannitol, or adenosine monophosphate (AMP) to assess the effect of inhaled corticosteroids were selected. RESULTS: Stimuli acting indirectly result in the release of a variety of bronchoconstricting mediators such as leukotrienes, prostaglandins, and histamine, from cells such as mast cells and eosinophils. A positive response to indirect stimuli is suggestive of active inflammation and AHR that is consistent with a diagnosis of asthma. Persons with a positive response to indirect stimuli benefit from daily treatment with inhaled corticosteroids. Symptoms and lung function are not useful to predict the long-term success of inhaled corticosteroid dose as they usually resolve rapidly, and well before inflammation and AHR has resolved. Following treatment, AHR to indirect stimuli is attenuated. Further, during long-term treatment, asthmatics can become as non-responsive as non-asthmatic healthy persons, suggesting that asthma is not active. CONCLUSIONS: Non-responsiveness to indirect bronchial provocation tests following inhaled corticosteroids occurs weeks to months following the resolution of symptoms and lung function. Non responsiveness to indirect stimuli may provide a goal for adequate therapy with inhaled corticosteroids. PMID- 20298273 TI - Risk factors associated with allergic and non-allergic asthma in adolescents. AB - INTRODUCTION: Risk factors for asthma have been investigated in a large number of studies in adults and children, with little progress in the primary and secondary prevention of asthma. The aim of this investigation was to investigate risk factors associated with allergic and non-allergic asthma in adolescents. METHODS: In this study, 959 schoolchildren (13-14 years old) answered a questionnaire and performed exhaled nitric oxide (NO) measurements. All children (n = 238) with reported asthma, asthma-related symptoms and/or increased NO levels were invited to a clinical follow-up which included a physician evaluation and skin-prick testing. RESULTS: Asthma was diagnosed in 96 adolescents, whereof half had allergic and half non-allergic asthma. Children with both allergic and non allergic asthma had a significantly higher body mass index (BMI) (20.8 and 20.7 vs. 19.8 kg/m(2)) (p < 0.05) and a higher prevalence of parental asthma (30% and 32% vs. 16%) (p < 0.05). Early-life infection (otitis and croup) [adjusted odds ratio (OR) (95% confidence interval (CI)): 1.99 (1.02-3.88) and 2.80 (1.44-5.42), respectively], pets during the first year of life [2.17 (1.16-4.04)], window pane condensation [2.45 (1.11-5.40)] and unsatisfactory school cleaning [(2.50 (1.28 4.89)] was associated with non-allergic but not with allergic asthma. CONCLUSION: This study indicates the importance of distinguishing between subtypes of asthma when assessing the effect of different risk factors. While the risk of both allergic and non-allergic asthma increased with increasing BMI, associations between early-life and current environmental exposure were primarily found in relation to non-allergic asthma. PMID- 20298274 TI - Vitamin and mineral status in elderly patients with chronic obstructive pulmonary disease. AB - INTRODUCTION: Eating problems are common in patients with chronic obstructive pulmonary disease (COPD), and intake of micronutrients might be lower than recommended. OBJECTIVE: To study dietary intake, serum and urinary concentration of trace elements and vitamins in elderly underweight patients with established severe COPD. METHODS: Outpatients at a university clinic for lung medicine, with COPD, 70-85 years old, with no other serious disease, and with a body mass index (BMI) of 2). Measurements of exhaled nitric oxide (eNO), serum levels of eosinophil cationic protein (ECP), eosinophil peroxidase, myeloperoxidase and human neutrophil lipocalin were made at each provocation. A 17-day symptom and peak flow diary was calculated. RESULTS: No differences between the two groups were found, regarding responsiveness to methacholine, adenosine or cold air challenge, as well as the inflammatory markers measured. In the infected group, the mean (standard deviation) ECP was higher in those with AHR to methacholine or cold air [15.7 (6.5) and 11.4 (4.2) microg/L, respectively; P < 0.05]; furthermore, eNO was higher in the infected group [116 (54) and 88 (52) nL/min, respectively; P = 0.055]. The infected group had, at all times, more symptoms and higher peak flow, with a decrease in the symptoms (P = 0.02) and a tendency to change in peak flow variation (P = 0.06). CONCLUSION: AHR does not seem to be the main cause of asthma-like symptoms in adults with infectious wheezing. Peak flow variation and symptom prevalence during the post infection period may imply airway pathology different from AHR. PMID- 20298278 TI - Educational case. PMID- 20298279 TI - Added value of combined simultaneous lung ventilation-perfusion single-photon emission computed tomography/multi-slice-computed tomography angiography in two patients suspected of having acute pulmonary embolism. PMID- 20298283 TI - Sarcoidosis: a view from afar. PMID- 20298284 TI - Clinical aspects and immune reactions in sarcoidosis. AB - INTRODUCTION: Sarcoidosis is a granulomatous disorder of unknown aetiology, affecting young adults and frequently involving the lungs. OBJECTIVE: The aim of the present review was to give an overview of the clinical aspects in sarcoidosis. RESULTS: The majority of patients recover, but some develop a chronic disease that may result in fibrosis and respiratory failure. Besides the lungs, peripheral lymph nodes, the skin, the liver and the eyes are commonly affected as well. The genetic background, as well as environmental factors, is of importance for developing sarcoidosis. The incidence varies in different populations, in the Nordic countries approximately with 20/100 000 new patients yearly. Sarcoidosis is diagnosed when clinical and radiological findings are supported by histological evidence in the form of non-caseating epithelioid cell granulomas, and when other causes of these features are excluded. Patients in need of treatment are usually treated with corticosteroids, topically or as oral steroids. A clinical effect of immunomodulatory drugs blocking tumour necrosis factor (TNF)alpha has been suggested from several case reports, while two controlled studies showed only minor effects; however, with a tendency to a more pronounced effect on patients with a more severe disease. The immune response in sarcoidosis, with a typical accumulation of CD4+ T-cells to the lungs, indicate the existence of specific antigens in this disease. Recently, antigens derived from infectious agents such as Mycobacteria and Proprionibacterium acnes have come into focus. Lymphocyte populations with immunoregulatory functions have recently been investigated and seem to be dysfunctional in sarcoidosis, opening the possibility of developing new treatment strategies in this disease. CONCLUSION: Recent technical developments have provided better tools, enabling detailed and more thorough analyses of the inflammatory process in sarcoidosis. PMID- 20298285 TI - Blau syndrome-associated mutations in exon 4 of the caspase activating recruitment domain 15 (CARD 15) gene are not found in ethnic Danes with sarcoidosis. AB - BACKGROUND: Distinct mutations of the caspase activating recruitment domain 15 (CARD15) gene (also known as nucleotide-binding oligomerisation domain protein 2) on chromosome 16q are associated with the chronic granulomatous disease called Blau syndrome. Sarcoidosis is a systemic granulomatous disease, which has features in common with Blau syndrome. AIM: The aim of this study was to evaluate whether ethnic Danes with sarcoidosis have CARD15 mutations associated with Blau syndrome. METHODS: Analysis of exon 4 of the CARD15 gene containing mutations associated with Blau syndrome was performed by polymerase chain reaction and sequencing of genomic DNA from 52 patients with histologically verified sarcoidosis. RESULTS: None of the patients had mutations in CARD15 associated with Blau syndrome. Eight other variations were found in exon 4: single nucleotide polymorphism (SNP)6 in 40% of the 104 alleles examined, SNP7 in 26%, c. 1833 C > T and SNP8 in 4%, c. 2107 C > T in 2%, and c. 931 C > T, c. 1292 C > T and c. 2377 G > A in 1%. One variation was found in intron 4 (IVS4 + 10 A > C) in 3% of the alleles. The frequencies of the variations in sarcoidosis patients were not statistically significant compared with frequencies in a control group of 103 healthy subjects. The course of disease was not significantly different in patients with or without variations in CARD15 or in the 46 patients with SNP6 and/or SNP7. CONCLUSIONS: Danish sarcoidosis patients have frequent variations in CARD15 exon 4, but do not present any mutation associated with Blau syndrome. The variations found had no influence on the course of disease. PMID- 20298286 TI - The effects of hypoxia and hypercapnia on renal and heart function, haemodynamics and plasma hormone levels in stable COPD patients. AB - BACKGROUND: Fluid retention with oedema is an important clinical problem in advanced chronic obstructive pulmonary disease (COPD). OBJECTIVE: The aim of this study was to investigate cardiovascular, hormonal, renal and pulmonary function data and their possible relation to fluid retention in COPD. METHODS: The study group consisted of 25 stable outpatients with COPD. The presence of oedema was assessed by clinical examination and the intake of diuretics was recorded. Glomerular filtration rate (GFR) and the renal blood flow (RBF) were measured. Lung function was assessed with standard spirometry. Cardiac function and haemodynamic variables were studied using echocardiography and equilibrium radionucleotide angiography. The plasma levels of noradrenaline, plasma renin activity, angiotensin II, aldosterone, atrial natriuretic peptide, brain natriuretic peptide and antidiuretic hormone were measured. RESULTS: Systolic and diastolic cardiac functions were found to be well preserved in the patients. Hypercapnia and impaired lung function, but not hypoxia, were clearly associated with oedema/intake of diuretics, low diuresis, low GFR, low RBF and high renal vascular resistance. These effects had no significant relationship to central haemodynamics or the measured plasma hormone levels. CONCLUSIONS: In stable COPD, renal fluid retention and oedema are enhanced by hypercapnia-induced renal vasoconstriction and antidiuresis. In contrast to some earlier reports, this effect does not seem to be mediated via the central haemodynamic reflex systems or the measured plasma hormones. In addition, hypoxia had no significant effect on fluid retention in this group of patients. PMID- 20298287 TI - Utility of hypertonic histamine challenge in distinguishing difficult-to-diagnose asthma. AB - INTRODUCTION: Although classical asthma is associated with airway hyperresponsiveness (AHR), this condition is also present in many cardiopulmonary disorders undermining the rational basis of its measurement in the differential diagnosis of asthma. We have recently introduced a new method to investigate AHR, the hypertonic histamine challenge (HHC). OBJECTIVE: The aim of this study was to evaluate the differential diagnostic power of HHC in a clinically representative sample of 138 patients. METHODS: Fifty-seven patients from the outpatient clinic of the authors' hospital with symptoms indicative of asthma were consecutively recruited. Asthma was confirmed in 31 subjects. The remaining 26 subjects formed the control group, in conjunction with seven patients with COPD, 15 patients with interstitial lung disease, 21 patients with rhinitis, 13 patients with heart failure and 25 healthy controls. Hypertonic histamine solution was administered with an ultrasonic nebuliser. RESULTS: Only the PC(20) values of asthmatic subjects differed statistically significantly from those of the healthy group (P < 0.0001). The receiver operator characteristic curve indicated that a PC(20) value of 0.83 mg/mL would be the optimal cut-off point of HHC to separate the asthmatics from the symptomatic controls with a sensitivity of 81% and specificity of 70%. With the PC(20) values of 0.1 and 4.0 mg/mL, the sensitivities were 42% and 100%, and the specificities were 96% and 40%, respectively. In these limits, HHC either confirmed or excluded asthma in 64 out of 138 patients (46%). CONCLUSION: The authors' attempt to improve the accuracy of the airway challenge test by combining direct and indirect challenges did not overcome the diagnostic limitations of previously utilised airway challenges. PMID- 20298288 TI - 'You have to learn to live with it': a qualitative and quantitative study of older people with asthma. AB - INTRODUCTION: Asthma mortality has declined overall because of a range of public health initiatives. In western countries, the majority of asthma deaths now occur in people over the age of 50. The reasons for the poorer response of older age groups to public health asthma initiatives are not known. OBJECTIVES: We undertook a study to investigate the disease perspectives of older people with asthma and barriers which may exist and prevent optimal asthma care. METHODS: Fifty-five participants (16 male and 39 female) aged over 50 from an inner city, suburban area and a rural region were recruited. Lung function was measured, and questionnaire data on asthma symptoms, knowledge and control, medication use and respiratory health were collected. Participants were also interviewed in-depth, and the quantitative and qualitative data were triangulated. RESULTS: Participants with a duration of asthma for >30 years reported significantly fewer symptoms and better quality of life irrespective of asthma severity, indicating less appreciation of symptoms in those with a long asthma duration. Interviews revealed this was related to previous asthma management strategies when treatment options were limited. Participants with a recent diagnosis sought understanding of asthma and the reason for their illness. Initiatives to improve asthma care in older people need to reflect these findings. CONCLUSIONS: Self-management strategies for older people need to be tailored according to the time of disease onset and the duration of disease. PMID- 20298289 TI - Does tumour necrosis factor-alpha inhibitor infliximab induce histological resolution of pulmonary sarcoid granulomas? AB - BACKGROUND: Sarcoid granuloma formation involves the orchestration of cytokines and chemokines, which modulate the host's immune response to the antigen stimulus. The release of cytokines enhances expression of the pro-inflammatory cytokine tumour necrosis factor-alpha (TNF), which plays a crucial role in the formation of sarcoid granuloma, being released from T-lymphocytes and alveolar macrophages. OBJECTIVE: The aim of this study was to evaluate the effect of infliximab in a case of pulmonary sarcoidosis using a histological approach. MATERIALS AND METHODS: A 44-year-old man with biopsy verified chronic pulmonary sarcoidosis being resistant to treatment with corticosteroids and cell cycle inhibitors. Persisting disease activity was confirmed by declining lung function tests and a positive fluorine-18-fluorodeoxyglucose-positron emission tomography scan. The patient was treated with a single course of infliximab 3-mg/kg body weight; 11 days later, a single lung transplantation was performed. Immunohistological staining with the macrophage marker CD68 was performed on lung tissue and mediastinal lymph node tissue from both the initial diagnostic evaluation (prior to infliximab) as well as from the explanted lung (after infliximab). RESULTS: Biopsy specimens from lung and mediastinal lymph nodes prior to infliximab demonstrated sarcoid granulomas, and staining with CD68 showed dense infiltration by macrophages (epithelioid cells) in the central part of the granulomas. In contrast, biopsies from the explanted lung after infliximab demonstrated acellular sarcoid granulomas with central amorphous masses, and staining with CD68 showed complete absence of macrophages. CONCLUSIONS: In this patient, the TNF inhibitor infliximab appeared to induce resolution of sarcoid granulomas starting with disappearance of macrophages probably caused by cell lysis or apoptosis. PMID- 20298291 TI - Increased awareness of COPD in the Norwegian population. PMID- 20298290 TI - Pulmonary manifestations of peripheral T-cell lymphoma: case report and review of the literature. AB - INTRODUCTION: Peripheral T-cell lymphomas (PTCL) represent approximately 10% of non-Hodgkin's lymphomas. Pulmonary involvement is an uncommon manifestation of this heterogeneous group of malignancies. METHODS: Report of a case. RESULTS: This case report describes a 75-year-old man with fever, weight loss, anemia, enlargement of spleen and liver, atypical lymphocytes and pulmonary nodules. Lung biopsy showed lymphocytic infiltration of the lung parenchyma. T-cell receptor gamma gene rearrangement by polymerase chain reaction confirmed the diagnosis of peripheral T-cell lymphoma. Unfortunately, the patient died because of refractory and aggressive disease. CONCLUSION: Pulmonary and pleural involvement are seen in patients with PTCL and usually carry a poor prognosis. The subject of pulmonary involvement in peripheral T-cell lymphoma is discussed. PMID- 20298292 TI - Yellow nail syndrome: treatment with octreotide. AB - INTRODUCTION: The yellow nail syndrome (YNS) is the triad of 'yellow' nails, peripheral oedema and pleural effusions. For diagnosis, which is clinical, at least two of these findings are necessary. Also typical is a long-standing chronic cough often caused by low-grade bronchiectases. The pleural effusions often require pleurodesis. The pathogenesis is probably a dysfunction of the lymphatic system (1, 2). Octreotide regulates the release of growth hormone and thyrotropin, and also has effects on the gastro-intestinal tract, where it inhibits glandular secretion, neurotransmission, smooth-muscle contraction and absorption of nutrients. Adverse effects are nausea, abdominal cramps, diarrhoea, malabsorption of fat and flatulence (3). Because of the inhibition of absorption of fats and other nutrients, octreotide has been useful in chylothorax from many different causes (4). The pleural effusion in YNS is usually an exudate, but in rare cases a frank chylothorax. One such case with successful octreotide treatment has been described in the literature (5). OBJECTIVE: The aim of this report was to investigate the effect of octreotide treatment on a patient with YNS with pleural exudates not resulting from chylothorax. METHODS AND RESULTS: A 62-year-old man with typical YNS presented with bilateral large pleural effusions (Fig. 1). He had suffered from repeated pneumonia for many years, and 10 years earlier mild bronchiectases were diagnosed and yellow nails were noted. From the right pleura, 1750-mL clear yellowish fluid was removed and a few days later, 1300 mL was removed from the left side. During the next few weeks, repeated thoracocenteses on both sides were necessary for the palliation of his dyspnoea, and the total amount of removed fluid was more than 10 L. The pleural fluid showed a low cholesterol value, 1.2 mmol/L (serum, 3.5), a fairly high albumin level, 19.0 g/L [serum, 25 g/L (normal, 36-45)], and no triglycerides. Octreotide was administered, initially 0.5 mg subcutaneously twice daily to make sure that there were no side effects, then the long-acting drug, 30 mg given every fourth week. There was a subjective improvement after the first week, and even though he still has pleural effusions bilaterally, he no longer needs palliative thoracocenteses and can live a normal life. His nails are better, as is the oedema. He is satisfied with his treatment and does not wish to have any pleurodesis. The observation time is now 6 months, and no adverse side effects have been seen so far. CONCLUSION: Octreotide can be tried in cases of YNS before more aggressive therapies are started. However, the best results are probably achieved in the rare cases where the effusion is a chylothorax. The other symptoms, such as yellow nails and oedema, also seemed to improve but evaluation is difficult because even normally, there are variations over time with these symptoms. Pleurodesis will probably be necessary in the future for our patient despite his octreotide treatment. Further studies are warranted in this rare disease. PMID- 20298293 TI - Educational case: dysphagia caused by lymphadenopathy--what is the differential diagnosis? PMID- 20298294 TI - 18F-fluoro-deoxyglucose PET for monitoring treatment in sarcoidosis. PMID- 20298297 TI - Reversing the tide of COPD: smoking cessation. PMID- 20298298 TI - Cessation in the use of tobacco - pharmacologic and non-pharmacologic routines in patients. AB - INTRODUCTION: Approximately one-third of the adult population in industrial countries and 70% in several Asian countries are daily smokers. Tobacco is now regarded as the world's leading cause of death. Approximately two-thirds of lifelong smokers eventually die because of smoking. Smoking cessation is the most effective action to reduce mortality in patients with chronic obstructive pulmonary disease (COPD) and coronary heart disease. OBJECTIVE: The aim of this study was to determine the effectiveness of smoking cessation programmes in patients with smoking-related disorders. METHODS: Medline was searched for studies of interventions for smoking cessation in patients. RESULTS: In patients with cardiovascular diseases and COPD, smoking cessation programmes with behavioural support over several months significantly increase quit rates. The intensity of the programmes seems to be proportional to the effect. A long follow up period is probably the most important element in the programmes. Even the most intensive programmes are very cost-effective in terms of cost per life-year gained. Effective programmes can be delivered by personnel without special education in smoking cessation using simple intervention principles. CONCLUSIONS: In patients with smoking-related disorders, smoking cessation interventions with several months of follow-up are effective and easily applicable in clinical practice. Wider implementation of such programmes would be a cost-effective way of saving lives. PMID- 20298299 TI - Low awareness of COPD among physicians. AB - INTRODUCTION: Early identification of patients with chronic obstructive pulmonary disease (COPD) in the health care system followed by successful smoking cessation may prevent rapid lung function deterioration, development of severe COPD and respiratory failure. OBJECTIVES: The aim of this study was to determine the frequency of under-diagnosed chronic obstructive lung diseases among current smokers. MATERIALS AND METHODS: The under-diagnosis of COPD among smokers was determined in subjects who participated in a screening procedure aimed at recruiting COPD patients for a smoking cessation programme. In order to identify current smokers, a questionnaire was sent out to persons who had been on sick leave for various reasons certified by a physician for more than 2 weeks. Subjects who stated that they currently smoked more than eight cigarettes per day were invited to perform a lung function test. RESULTS: A total of 3887 subjects performed spirometry, i.e. forced expiratory volume in 1 s and forced expirations, and among these, 674 (17.3%) had COPD according to the European Respiratory Society (ERS) consensus guidelines. Of those, 103 (17.3%) had physician-diagnosed COPD. Productive cough was reported by 16.6% of the COPD subjects. Despite the fact that smokers were on sick leave certified by a physician, more than 80% of those with COPD had no previous diagnosis. As the COPD diagnosis cannot be based on reported symptoms, a spirometry on persons at risk must be performed. CONCLUSION: The awareness of COPD among primary care physicians has to increase and smokers above the age of 40, with and without respiratory symptoms, have to undergo spirometry if it is regarded important to establish the COPD diagnosis at an early stage. PMID- 20298300 TI - Identification of patients with chronic obstructive pulmonary disease (COPD) by measurement of plasma biomarkers. AB - INTRODUCTION: Inflammation is an important constituent of the pathology of chronic obstructive pulmonary disease (COPD), leading to alveolar destruction and airway remodelling. OBJECTIVE: The aim of this study was to assess the difference in plasma biomarkers of inflammation between asymptomatic smokers and patients with COPD. METHODS: We used commercially available enzyme-linked immunosorbent assay kits to measure the plasma levels of tumour necrosis factor-alpha (TNF alpha), interleukin-8 (IL-8), matrix metalloproteinase-9 (MMP-9), monocyte chemotactic protein-1 (MCP-1), tissue inhibitor of metalloproteinase-1 (TIMP-1) and tissue inhibitor of metalloproteinase-2 (TIMP-2) on two occasions with a 2 week interval in patients with COPD (n = 20), asymptomatic smokers (n = 10) and healthy lifelong non-smokers (n = 10). The participants were characterised clinically, physiologically and by quantitative computed tomography by measuring the relative area of emphysema below -910 Hounsfield units (RA-910). RESULTS: The results of the biomarker measurements on the two occasions were highly reproducible. Patients with COPD had significantly higher plasma levels of IL-8 (P = 0.004) and significantly lower levels of TIMP-1 (P = 0.02) than smokers and non-smokers. There was no statistically significant difference between the three groups in the level of TNF-alpha, MMP-9, MCP-1 and TIMP-2. The IL-8/TIMP-1 ratio correlated significantly with the degree of airway obstruction measured as forced expiratory volume in 1 second (FEV(1)) % predicted (r = -0.47, P < 0.01); with the diffusion capacity (r = -0.41, P < 0.01); and with the grade of emphysema measured as RA-910 (r = 0.39, P = 0.01). CONCLUSION: These findings suggest that the measurement of plasma biomarkers, such as IL-8/TIMP-1, may aid to discriminate patients with COPD from smokers at lower risk of developing COPD. PMID- 20298301 TI - Impact of home mechanical ventilation on health-related quality of life in patients with chronic alveolar hypoventilation: a prospective study. AB - BACKGROUND: Nocturnal ventilatory support by nasal positive pressure ventilation (NPPV) is an established treatment method in patients with chronic alveolar hypoventilation (CAH). The knowledge about its long-term effects on health related quality of life (HRQL) is limited. METHODS: In a prospective, longitudinal, single-strand study, patients with CAH caused by non-COPD conditions, consecutively recruited among referral patients in three Swedish university hospital pulmonary departments, were examined at baseline and after 9 months (n = 35) and 8 years (n = 11) on NPPV treatment. Both volume pre-set and pressure pre-set ventilators were used. Patients completed a battery of condition specific and generic HRQL questionnaires at baseline and follow-up. Spirometry and blood gases were measured. Compliance with treatment, side effects and patient satisfaction were evaluated. RESULTS: After 9 months of NPPV, improvements were seen primarily not only in sleep-related domains, but also in emotional behaviour, ambulation and sleep/rest functioning as measured with the Sickness Impact Profile (SIP). Improvements in sleep-related symptoms were related to effectiveness in ventilation, evaluated by morning PaCO(2), and remained by 8 years. Mental well-being was stable over time, while emotional distress improved by 8 years. Satisfaction with treatment was high in spite of frequent side effects. CONCLUSION: NPPV improves HRQL, particularly in condition specific areas. Improvements are related to effectiveness in ventilation. Side effects are common, but compliance is good and patient satisfaction is high. PMID- 20298302 TI - Inspiratory capacity and forced expiratory volume in the first second in exacerbation of chronic obstructive pulmonary disease. AB - OBJECT: Periodic exacerbations of symptoms are the major cause of morbidity, mortality and health care costs in patients with chronic obstructive pulmonary disease (COPD). Dyspnea is the major factor affecting the comfort of patients in the exacerbation of COPD. In this study, we aimed to compare the value of forced expiratory volume in the first second (FEV(1)) and inspiratory capacity (IC) measured before and after treatment in exacerbations and in the improvement in dyspnea. METHODS: Eighty-seven patients (male/female, 80/7; mean age, 63 +/- 7) with COPD exacerbation were included in this study. All subjects underwent spirometric tests on the first day and at the end of treatment. The subjects were asked to quantify the sensation of dyspnea that was described to them as a nonspecific discomfort associated with the act of breathing. The patients quantified dyspnea by pointing to a score on a large Borg scale from 0 to 10 arbitrary units. In the beginning and at the end of treatment, forced vital capacity (FVC), FEV(1), forced expiratory flow rate between 25% and 75% of FVC (FEF25-75), peak expiratory flow rate (PEF), IC and Borg score (BS) values were compared. RESULTS: After treatment of COPD exacerbations, FEV(1), FEF25-75, PEF and IC significantly increased, and the BS significantly decreased compared to the initial values. The increase in IC was more significantly correlated with the improvement in BS compared with FEV(1). Admission and discharge day BS was negatively correlated with FEV(1), FEF25-75 and IC. CONCLUSION: We have shown a more dramatic improvement in IC compared with FEV(1) in patients treated as a result of acute exacerbation of COPD. These data suggest that IC may be more useful than FEV(1) during acute exacerbation of COPD. Moreover, IC better reflects the severity of dyspnea in these patients. PMID- 20298303 TI - Smoking reduction and cessation reduce chronic cough in a general population: the Inter99 study. AB - BACKGROUND: Chronic cough can be the first sign of chronic obstructive disease. A few, and mostly selected, studies exploring the effect of reduced daily tobacco consumption have shown a small effect on pulmonary symptoms. AIM: The aim of this study was to examine if smoking reduction (SR) (> or =50% of daily tobacco consumption) or smoking cessation (SC) had an effect on chronic cough and phlegm. METHODS: A total of 2408 daily smokers were included in a Danish population-based intervention study, Inter99. In the analyses, we included smokers with self reported chronic cough or phlegm at baseline who also attended the 1-year follow up. We investigated if SR or SC had improved the self-reported pulmonary symptoms, using logistic regression analyses. RESULTS: Almost 34% of the smokers had chronic cough at baseline and 24.5% had chronic phlegm. Thirty-seven persons with cough at baseline and 24 with phlegm at baseline achieved substantial SR at 1-year follow-up. The corresponding numbers for SC were 63 and 39, respectively. In adjusted analyses, quitting or reducing smoking was associated with less reporting of cough [odds ratio (OR): 14.2; 95% confidence interval (CI): 5.9 34.4] and (OR: 3.7; 95% CI: 1.7-8.0), respectively, compared with unchanged smoking habits. It was also significantly more likely not to report phlegm at 1 year follow-up for those who had quit (OR: 7.1; 95% CI: 2.8-18.0), whereas SR was not significantly associated with termination of phlegm (OR: 2.5; 95% CI: 0.9 6.4) when compared with continuous smoking. CONCLUSION: SC significantly improved self-reported chronic cough and phlegm as expected. Substantial SR was achieved by few smokers but had a significantly positive effect on chronic cough. PMID- 20298304 TI - Can one single test protocol for provoking exercise-induced bronchoconstriction also be used for assessing aerobic capacity? AB - INTRODUCTION: Several different exercise protocols are used to assess exercise induced bronchoconstriction (EIB), and to measure peak oxygen uptake (VO(2 peak)) and peak minute ventilation (VE(peak)). OBJECTIVE: The aim of this study was to evaluate if one single test protocol for assessing EIB can also be used to determine aerobic capacity measured by VO(2 peak) and VE(peak). METHODS: In a randomised cross-over design, 40 healthy subjects (female symbol/male symbol = 17/23) aged 14-40 years performed two exercise tests on a treadmill. Twenty subjects (female symbol/male symbol = 7/13) performed the two exercise tests at a treadmill inclination of 10.5%; the remaining 20 subjects (female symbol/male symbol = 10/10) performed at an inclination of 5.3%. A common stepwise protocol with 20 min of warming up was compared to an EIB test protocol of an 8-min treadmill run without warming up, with a workload corresponding to 95% of maximum heart rate during the last 4 min. RESULTS: VO(2 peak) did not differ significantly between the two test protocols at 10.5% inclination: 63.3 mL/kg min(-1)(59.3, 67.4) [mean (95% confidence intervals)] and 63.9 mL/kg min(-1) (60.0, 68.0), respectively, or at 5.3% inclination: 56.0 mL/kg min(-1) (52.1, 60.0) and 56.1 mL/kg min(-1) (51.9, 60.2), respectively. Also, VE(peak) did not differ between the protocols 158 (144, 173) vs 161 L/min (145, 176) at 10.5% inclination and 123 (114, 132) vs 127 L/min (116, 138) at 5.3% inclination, with the EIB protocol and the stepwise protocol, respectively. CONCLUSION: VO(2 peak) and VE(peak) did not differ between the two test protocols, and one single standardised EIB test may thus be used both for both provoking EIB and assessing VO(2 peak). PMID- 20298305 TI - Treatment and evaluation of patients with acute exacerbation of asthma before and during a visit to the ER in Denmark. AB - BACKGROUND: Acute exacerbation of asthma may be life-threatening and quite often results in a visit to the emergency room (ER) or admission to a hospital. The aim was to evaluate the treatment and the quality of clinical management of asthma exacerbations, and finally, to identify the factors leading to admission. MATERIAL AND METHODS: In a retrospective design, we audited the hospital records of all patients aged 18-40 years admitted to five Danish university hospitals with an acute exacerbation of asthma in 2004. RESULTS: We found records covering 323 asthmatic patients (186 women). Before admission, the mean (standard deviation) duration of the exacerbation was 5.2 (7.5) days. Of those admitted, 14% did not use any medication, 39% used inhaled corticosteroids (ICS) either with a beta(2)-agonist or alone, systemic steroids, and 34% used a beta(2) agonist alone. Lung function (peak flow or forced expiratory volume in first second) was measured in 60% on admission, in 58% on discharge and in 47% on both occasions (P < 0.01). Temperature, heart rate and oxygen saturation were measured in 231 of the patients (72%), but the respiratory frequency rate was measured in only 16% of the patients, with some differences between the five hospitals. On discharge, 50% were treated with systemic steroids, and a further 20% had ICS prescribed (P < 0.01, admission vs discharge). In 21% of the cases, inadequate treatment was identified as the most likely reason for their ER visit/admission to a hospital. CONCLUSIONS: The assessment and treatment of patients admitted with acute asthma exacerbation was often suboptimal. Under-treatment with the anti-asthmatic medication was the main reason for admission. PMID- 20298306 TI - Subcarinal bronchogenic cyst. PMID- 20298307 TI - Setting up an ambulatory sleep research unit. PMID- 20298308 TI - Novel lung cancer staging algorithms. PMID- 20298309 TI - Diagnostics and staging procedures in non-small cell lung cancer - is less more? AB - INTRODUCTION: Non-small cell lung cancer (NSCLC) is a common cancer with approximately 85% of patients dying of the disease. The only chance for cure is in the early stages, when surgery or definite chemoradiotherapy can be performed. Diagnosis and staging of lung cancer can sometimes be difficult, particularly because the intrathoracic structures are not easy to reach. OBJECTIVE: This review discusses the diagnosis and staging of lung cancer. RESULTS: When performing lung cancer diagnostics, both invasive and noninvasive procedures, such as computed tomogram of the chest, bronchoscopy and abdominal ultrasound, are mandatory. Suspected mediastinal involvement should be differentiated: bulky disease, contralateral or high mediastinal nodes need further clarification by endoscopic ultrasound, endobronchial ultrasound or mediastinoscopy. In opposition to current guidelines, in all other cases, surgery should be performed. Positron emission tomography will gain even more importance when becoming widely accessible and might replace other imaging techniques in the future. In case of advanced disease, staging should be limited to those examinations with impact on symptom control. CONCLUSION: The diagnosis and staging of lung cancer should involve both invasive and noninvasive diagnostic procedures. In the case of advanced disease, staging should be limited to those examinations with impact on symptom control, whereas early stages call for rapid and thorough diagnosis. PMID- 20298310 TI - Current concepts in chemotherapy for malignant pleural mesothelioma. AB - OBJECTIVES: The aim of this study was to provide an overview of the most active single agents and combination regimens in malignant pleural mesothelioma (MPM). DATA SOURCE: Literature on English-language trials in humans was searched on Medline until October 2007. Indexing terms were malignant pleural mesothelioma and chemotherapy. STUDY SELECTIONS: Trials with > or =15 patients and with data on activity were included. RESULTS: Detorubicin and pirarubicin have response rates (RRs) of 22%-26%, epirubicin of 5%-15%, docetaxel of 5%-23% and vinorelbine of 24%. Other active agents were ifosfamide (3%-24%) and mitomycin C (21%). Carboplatin and cisplatin have an overall RR of 11% in three studies and 17% in four studies, respectively. Antimetabolites were active, including methotrexate (37%), raltitrexed (21%), edatrexate (16%-25%) and pemetrexed (15%). With respect to combination chemotherapy regimens, only cisplatin with either pemetrexed or raltitrexed has been compared with other substances, in both cases to cisplatin monotherapy. Both showed a survival advantage, which was statistically significant in the trial including pemetrexed, suggesting that chemotherapy improved survival in MPM. No studies have compared chemotherapy with the best supportive care alone, and none has compared different combination chemotherapy regimens with each other. CONCLUSIONS: A number of single-agent cytotoxics posess moderate activity against MPM. A number of platinum-based combination chemotherapy regimens show similar activities, but none has been compared with another combination. Cisplatin with either raltitrexed or pemetrexed has improved survival compared with cisplatin alone, and may be used as a reference treatment in randomized trials. Targeted agents should be explored in order to further improve the outcome. PMID- 20298311 TI - Treatment of malignant pleural mesothelioma with liposomized doxorubicine: prolonged time to progression and good survival. A Nordic study. AB - INTRODUCTION: Malignant pleural mesothelioma (MPM) has a poor prognosis and there is limited effect of treatment. Lately, pemetrexed and cisplatin have been established as the standard treatment. OBJECTIVES: The present study was planned in 1998, when there was no standard treatment. Single-dose doxorubicine had, in small studies, accomplished remissions, and the Scandinavian Mesothelioma Groups therefore decided to test a liposomized form of this drug, which had shown limited toxicity but good efficacy in a few small studies. METHODS: Fifty-four evaluable patients with histologically verified and inoperable MPM were treated with liposomized doxorubicine 40 mg/m(2), every 4 weeks for six cycles. RESULTS: In all, 29 patients (54%) received at least six treatments. The quality of life remained good during the study. Hematologic toxicity was very low. Palmo-plantar erythema occurred in 11 patients (20%), thereof 7 grade II but none was severe and none was dose-limiting. There were four partial responses (7%). The median time to progression (TTP) was 5 months, the median survival was 12 months, and at 24 months, 22% were still alive. CONCLUSION: Liposomized doxorubicine has a low toxicity and is well tolerated; there were a remarkably long TTP and a good survival. Thus, despite the low response rate, liposomized doxorubicine remains an interesting drug for the treatment of malignant mesothelioma. PMID- 20298312 TI - A comparison between patients with dysfunctional breathing and patients with asthma. AB - INTRODUCTION: The term dysfunctional breathing (DB) has been introduced to describe patients who display a divergent breathing pattern and have breathing problems that cannot be attributed to a specific medical diagnosis such as asthma, chronic obstructive pulmonary disease or sensory hyper-reactivity. OBJECTIVE: The objective of this study was to investigate similarities and differences in patients with DB, and patients with well-controlled asthma regarding health-related quality of life, anxiety, depression, sense of coherence (SOC), hyperventilation and effects on daily life. METHODS: Twenty-five consecutive patients with DB, and 25 age- and sex-matched patients with asthma (ages 20-73 years) participated in the study. The diagnosis of DB was based on the presence of a dysfunctional breathing pattern and at least five symptoms associated with DB. RESULTS: The group with DB had lower health-related quality of life (short form 36): vitality (mean) 47 vs 62, social functioning 70 vs 94 and role emotional 64 vs 94 (P < 0.05) than the asthmatic group. The DB group also had a higher prevalence of anxiety (56% vs 24%) and a lower SOC (134 vs 156) (P < 0.05). Hyperventilation, defined according to the Nijmegen symptoms questionnaire, was observed in 56% of patients with DB vs 20% in the asthma group (P = 0.02). CONCLUSIONS: The results of the study indicate that patients with DB are more disabled than patients with well-controlled asthma. There is a great need for more knowledge about breathing symptoms of a dysfunctional nature, to be able to identify and manage these patients adequately. PMID- 20298313 TI - Asthma management in primary care: does increasing patient medication improve symptoms? AB - AIMS: We set out to observe the General Practitioner (GP) management of a cohort of asthma patients over a 2-year period by comparing asthma health status, spirometry, British Thoracic Society treatment step, inhaled medication uptake and psychological status. Changes in these parameters were assessed over the 2 year period. METHODS: One hundred fourteen subjects were recruited from four GP practices, two in the inner city and two in suburbia. Subjects were assessed at baseline and at 2 years using the Juniper asthma quality of life questionnaire, the locally devised Q score (a simple patient-focused morbidity index) and the hospital anxiety and depression (HAD) scale. Spirometry (forced expiratory volume in 1 s, forced vital capacity and peak expiratory flow) was recorded using a Micro Medical portable spirometer (Micro Medical Ltd, Chatham, UK); the best values from three acceptable attempts were recorded. RESULTS: Data for 90 subjects reviewed at baseline and at 24 months were compared to the original cohort of 114 subjects. Patients who had the treatment increased showed no apparent benefit over 2 years. They had similar physiology and symptom scores at baseline but had higher HAD scores (particularly depression element P < 0.05) initially. The picture remained constant over the 2 years. CONCLUSION: Asthma guidelines define the aim of treatment to minimise or abolish symptoms. We suggest that if the symptoms are not measured, they remain unrecognised. This is something that could and should be incorporated routinely into clinical practice because this is morbidity that is largely treatable. PMID- 20298314 TI - A video-simulation study of the management of asthma exacerbations by physicians in India. AB - INTRODUCTION: Despite efforts to improve the management of asthma worldwide, few options exist for evaluating the specific needs or the success of these activities in a manner free from bias. OBJECTIVES: To examine the management of asthma exacerbations by physicians using standardized audiovisual presentations of asthma. METHODS: Practitioners (n = 70) in Chennai, India were shown the International Study of Asthma and Allergies in Childhood video questionnaire and asked to describe the clinical investigations, emergency treatments and prescription therapy they would recommend for each of the five scenes. RESULTS: Practitioners varied significantly in their investigation and treatment of the exacerbations. Those who identified asthma as a possible cause of the scenes were more likely to recommend investigations and treatment congruent with international guidelines, as were those with additional postgraduate training and with specialty training in respiratory disease. Approaches differed significantly for scenes depicting wheeze compared with those depicting cough. CONCLUSION: The management of asthma exacerbations varies significantly depending on whether practitioners identify asthma as a possible cause of the presentation. Standardized audiovisual depictions of asthma offer a useful tool to assess patterns of clinical practice, and to design and evaluate activities to raise the quality of care for asthma. PMID- 20298315 TI - Asthma and health-related quality of life - effect of adjusting for potential confounders. AB - BACKGROUND: Health-related quality of life (HRQoL) is an increasingly important outcome measure in medical research. We wanted to evaluate how adjustment for potential confounders affected the relationship between HRQoL and asthma. Furthermore, we wanted to evaluate the relationship of environmental tobacco smoke (ETS) with HRQoL. METHODS: We carried out a cross-sectional Norwegian community study in 1996/1997 including 2306 randomly selected subjects aged 26 years-81 years. Data on HRQoL were measured by SF-12. The data were analyzed by robust linear regression analyses with the physical component score (PCS) and the mental component score (MCS) as dependent variables. The effect of adjusting for the potential confounders was analyzed by bootstrap confidence intervals for differences between the adjusted and unadjusted models. RESULTS: The difference in the asthma coefficients between the unadjusted and adjusted models for both PCS and MCS varied from 0.1 to 1.1. The confidence intervals for these differences for PCS were (-0.3, 1.6) and (0.4, 1.8), using the definition 'asthma last 12 months' and 'physician's diagnosis of asthma', respectively. The confidence intervals for the corresponding differences for MCS were (-0.01, 1.3) and (-0.6, 0.4), respectively. Univariately, PCS was lower among subjects reporting ETS at home compared to people not reporting ETS at home, but this difference did not persist in the multivariate analyses. ETS at home was associated with slightly improved MCS. CONCLUSION: Adjusting for potential confounders does not change the relationship between asthma and HRQoL overtly. PMID- 20298316 TI - Bacterial colonisation of lower airways in health and chronic lung disease. AB - BACKGROUND: To evaluate the colonisation rate and type in different groups of patients with chronic lung diseases, bronchial lavage (BL) fluid was investigated for bacteria. METHODS: All patients underwent fibre-optic bronchoscopy as part of routine investigation for remote haemoptysis or nodule investigation. The standard procedure included BL and microbiological culture providing the total number of colony forming units (cfu)/mL and the number of potential pathogenic bacteria (ppb)/mL. Three groups of patients were included: 48 persons had a final diagnosis of no pathology, 53 patients with chronic obstructive pulmonary disease in a stable phase and 32 patients with a final diagnosis of bronchiectasis. RESULTS: The median number of cfu cultured from patients with bronchiectasis was 10(5) cfu/mL compared to 5 10(3) cfu/mL in patients with COPD and 10(4) cfu/mL in persons with no pathology. The ppb colonisation rate varied from 10% in persons with no pathology to 43% in patients diagnosed with chronic obstructive pulmonary disease (COPD) and 63% in patients with bronchiectasis. The most frequent bacteria isolated was Haemophilus influenzae. Colonisation rates were associated with frequencies of respiratory infections; patients with bronchiectasis reported a median of three infections per year, patients with COPD reported one infection per year, and persons without pathology reported 0 infections per year (P < 0.05). Within each group a large patient-to-patient variation was found. CONCLUSIONS: Different groups of patients with chronic pulmonary diseases have very different colonisation rates. Patients with bronchiectasis have the highest colonisation rate. This correlates to the reported frequency of lower respiratory tract infections. PMID- 20298317 TI - Treatment of lobar atelectasis with bronchoscopically administered recombinant human deoxyribonuclease in cystic fibrosis? AB - INTRODUCTION: Recombinant human deoxyribonuclease (rhDNase) reduces sputum viscosity and improves pulmonary function in cystic fibrosis (CF). OBJECTIVE: The objective of this study was to describe our experience in which rhDNase (Pulmozyme; Roche, Basel, Switzerland) was administered by bronchoscopic instillation into atelectatic lobes in five adults with CF. CONCLUSION: We found this method successful in treating lobar atelectasis, which was resistant to conventional therapy with antibiotics and physiotherapy. In all but one of the cases we described, administration of DNase in this manner resulted in a radiographic and clinical improvement of the atelectasis. We recommend that respiratory physicians consider this as a second line treatment in the management of atelectasis. PMID- 20298319 TI - Adenocarcinoma. PMID- 20298318 TI - BCG vaccination and risk of atopic diseases in a twin cohort. PMID- 20298320 TI - One year anniversary. PMID- 20298321 TI - Emerging treatments for pulmonary arterial hypertension. AB - INTRODUCTION: Pulmonary arterial hypertension (PAH) is a rare, progressive disease for which no cure exists. However, improved understanding of underlying pathophysiological mechanisms has led to the development of several effective treatments that improve haemodynamics and functional status. OBJECTIVE: An overview of emerging pharmacological approaches to the management of PAH is presented. MATERIALS AND METHODS: A Medline search was performed for studies describing novel treatments and potential therapeutic targets relevant to PAH. RESULTS: Several different treatments that modulate abnormalities in the prostacyclin, endothelin and nitric oxide pathways have shown efficacy in randomised, controlled studies and are now licensed for use for PAH patients with advanced disease. Furthermore, there is now encouraging long-term survival data associated with use of these agents. A number of other targets with therapeutic potential have also been identified, such as serotonin, platelet-derived growth factor and vasoactive intestinal peptide. Recently, strategies involving combinations of different PAH-specific agents have emerged as a promising approach for those failing monotherapy. CONCLUSION: The therapeutic options available for PAH has improved considerably in recent years and is likely to expand in the future. PMID- 20298322 TI - Atopic sensitization to common allergens without symptoms or signs of airway disorders does not increase exhaled nitric oxide. AB - BACKGROUND: Elevated fractional exhaled nitric oxide (FENO) associates positively with symptomatic atopy among asthmatics and in the general population. It is, however, unclear whether sensitization to common allergens per se- as verified with positive skin prick tests--affects FENO in healthy individuals. OBJECTIVE: The aim of this study was to examine the association between FENO and sensitization to common allergens in healthy nonsmoking adults with no signs or symptoms of airway disorders. METHODS: FENO measurements (flow rate: 50 mL/s), skin prick tests to common inhalant allergens, structured interviews, spirometry, bronchodilatation tests and bronchial histamine challenges were performed on a randomly selected population of 248 subjects. Seventy-three of them (29%) were nonsmoking asymptomatic adults with no history of asthma, persistent or recurrent upper or lower airway symptoms and no signs of airway disorders in the tests listed above. RESULTS: FENO concentrations were similar in skin prick test positive (n = 32) and negative (n = 41) healthy subjects, with median values of 13.2 and 15.5 ppb, respectively (P = 0.304). No correlation appeared between FENO and the number of positive reactions (r = -0.138; P = 0.244), or the total sum of wheal diameters (r = -0.135; P = 0.254). The nonparametric one-tailed 95% upper limits of FENO among skin prick positive and negative healthy nonsmoking subjects were 29 and 31 ppb, respectively. CONCLUSIONS: Atopic constitution defined as positive skin prick test results does not increase FENO in healthy nonsmoking adults with no signs or symptoms of airway disorders. This suggests that same reference ranges for FENO can be applied to both skin prick test positive and negative subjects. PMID- 20298323 TI - Asthmatics able to step down from inhaled corticosteroid treatment without loss of asthma control have low serum eotaxin/CCL11. AB - INTRODUCTION: The addition of a long-acting beta2 agonist (LABA) to inhaled corticosteroid (ICS) may control asthma better than ICS alone. Eosinophil markers may predict symptom severity in asthma. OBJECTIVES: The effect of combination treatment on moderate to severe asthmatics not selected to respond rapidly to steroid deprivation was compared with monotherapy. The ability of serum markers to predict symptom severity was assessed. METHODS: Asthmatics treated adequately with ICS (750-1000 mcg ICS daily) were randomised to receive ICS (fluticasone propionate) + LABA (salmeterol) (500 mcg/50 mcg bd) or ICS alone (500 mcg bd). If asthma was controlled at clinic visits every 6 weeks, ICS dose was tapered until asthma exacerbated (hospitalisation, ICS above study medication, peak flow variation, decline in forced expiratory volume in 1 s and/or use of rescue medication), or placebo was maintained for 6 weeks. Efficacy of the treatments was compared. Serum cytokines and chemokines were compared among the groups reporting severe, mild or no symptoms. RESULTS: There was no difference between the treatment arms in the clinical analysis. Nine patients could be maintained on placebo for 6 weeks, 36 developed mild symptoms and 16 developed severe symptoms. Patients on placebo for 6 weeks had significantly lower serum eotaxin at baseline than patients with symptoms. Patients with mild symptoms had intermediate serum eotaxin concentrations. CONCLUSION: Patients with asthma controlled on ICS respond heterogeneously to ICS tapering. Serum eotaxin/CCL11 may be useful in predicting the severity of symptoms patients develop during steroid tapering and should be evaluated in guiding asthma treatment. PMID- 20298324 TI - The effectiveness of smoking cessation groups offered to hospitalised patients with symptoms of exacerbations of chronic obstructive pulmonary disease (COPD). AB - INTRODUCTION: Chronic obstructive pulmonary disease (COPD) is a major contributor to morbidity and mortality. Smoking is the leading cause of COPD. Results from randomised trials regarding smoking cessation in hospitalised patients with COPD are few. OBJECTIVES: To assess the effect of smoking cessation groups (SCG) in patients with COPD admitted to hospital. METHODS: Two hundred and twenty-three patients admitted to hospital were assigned to either a control group (n = 102) or an intervention group (n = 121) by matter of vacancy. The smokers in the intervention group were offered participation in an SCG. Smoking status and change in self-reported symptoms were assessed after 1 year. Smoking status was self-reported and verified with carbohemoglobin measurement. Survival and hospital admissions were assessed after 5 years through national registers. RESULTS: Forty-eight patients participated in an SCG. After 1 year, 36 (30%) patients in the intervention group were abstinent compared with 13 (13%) patients in the control group [odds ratio (95% confidence interval): 2.83 (1.40-5.74)]. There was a significant difference between the intervention group and the control group regarding change in self-reported phlegm. There was a non-significant tendency towards better survival in the intervention group (50.4%) compared with the control group (43.1%). After 3 years, the intervention group had a significantly fewer total number of days admitted to hospital and number of days hospitalised with COPD. CONCLUSION: This study shows that an intervention consisting of offering participation in an SCG to chronic patients makes it possible to obtain higher abstinence rates. Furthermore, this intervention showed impact on phlegm, survival and hospital readmissions. PMID- 20298325 TI - Increased exhaled nitrite in children with allergic asthma is not related to nitric oxide formation. AB - INTRODUCTION: Nitrite sampled from the upper airways could originate from inflammation-induced nitric oxide (NO), as reports of elevated nitrite in exhaled breath condensate (EBC) from asthmatics suggest, but also through bacterial action in the pharyngo-oral tract. OBJECTIVES: To correlate EBC nitrite and nitrate to exhaled NO (FENO, fraction of expired NO) and other markers of disease activity in children with allergic asthma and thereby further investigate their role and origin. MATERIALS AND METHODS: EBC was collected from 27 asthmatic subjects (ages 6-17 years, all immunoglobulin E-positive for aeroallergens) and 21 age-matched non-atopic healthy controls for fluorometric analysis of nitrite and nitrate. These markers were compared with measurements of FENO, blood eosinophil count (EOS), methacholine reactivity (PD(20)) and baseline spirometry. RESULTS: EBC nitrite, in contrast to nitrate, was significantly increased (P < 0.01) in the asthmatic children. They also had increased levels of FENO (P < 0.001) and EOS (P < 0.001) along with decreased PD(20) (P < 0.001) and FEV1/FVC (P < 0.01). However, there was no correlation between EBC nitrite and FENO (r = 0.05) or any other marker of disease activity in the asthmatic children, whereas between the other markers correlations could be established. CONCLUSION: EBC nitrite is elevated in childhood asthma but the lack of correlation to FENO and other markers, together with simultaneously normal levels of nitrate, make its origin as a metabolite of inflammation-induced NO questionable. PMID- 20298326 TI - Long-term effects of a preoperative smoking cessation programme. AB - INTRODUCTION: Preoperative smoking intervention programmes reduce post-operative complications in smokers. Little is known about the long-term effect upon smoking cessation. AIM: To discover long-term quit rates and the reasons behind successful cessation. MATERIALS AND METHODS: 101 one of 120 smokers, randomised to smoking intervention or no intervention before hip and knee surgery, completed questionnaires concerning smoking after 1 year. We selected representative men and women for focus group interviews. RESULTS: Significantly more patients from the intervention group abstained from smoking for 1 year post-operatively [13 in 60 patients (22%) vs 2 in 60 (3%), P < 0.01]. Sex (male), low nicotine dependency, non-smoking spouse and preoperative smoking intervention were related to smoking cessation. All patients gave the same reasons for smoking cessation: improved health and saving money. Follow-up for 5 years showed 17% of the controls and 8% in the intervention group (P = 0.42) had died. CONCLUSION: The intervention group had a significantly higher quit rate 1 year after a preoperative smoking cessation programme. PMID- 20298328 TI - An (un)usual cause of haemoptysis. PMID- 20298327 TI - An unusual cause of diffuse pulmonary haemorrhage. AB - INTRODUCTION: Diffuse pulmonary haemorrhage is a potentially life-threatening complication of a variety of conditions. Tumours, including angiosarcoma lung metastases, are an unusual cause of pulmonary haemorrhage. METHODS: Report of a case. RESULTS: This case describes a 38-year-old previously healthy male who presented with chest wall bruising followed by haemoptysis and a cerebellar haemorrhage. The patient developed diffuse pulmonary haemorrhage. A biopsy of the chest wall lesion indicated a haematoma and an open-lung biopsy suggested the diagnosis of vasculitis. The patient died within 3 months after initial presentation and an autopsy revealed a chest wall angiosarcoma with pulmonary and cerebellar metastases. CONCLUSION: Pulmonary angiosarcoma metastases should be included in the differential diagnosis of diffuse pulmonary haemorrhage, especially in a young, previously healthy patient with normal renal function, particularly as the pathological diagnosis may be difficult and even misleading. PMID- 20298329 TI - Congress report from the 43rd Nordic Lung Congress, Uppsala, Sweden. PMID- 20298330 TI - Different features of pulmonary hypertension in Rendu-Osler Syndrome. PMID- 20298332 TI - Don't sleep on it. PMID- 20298333 TI - Sleep apnoea--where are the physicians in respiratory medicine? PMID- 20298334 TI - Obstructive sleep apnoea syndrome: current status. AB - INTRODUCTION: Obstructive sleep apnoea syndrome (OSAS) is a prevalent condition that covaries with cardiovascular complications and most likely with arterial hypertension and diabetes mellitus. OBJECTIVE: The present paper is a review of the current status of OSAS. RESULTS: Definitions and diagnostic criteria as well as known risk factors, prevalence, symptoms, covariance with other diseases and consequences as traffic accidents are described. OSAS is characterised by daytime sleepiness symptoms that range from mild to severe. Risk factors such as anatomical upper airway abnormalities, overweight, smoking, excessive alcohol intake and use of muscle relaxants are related to the development of sleep apnoea. Various diagnostic procedures and treatment modalities are considered. Overnight polysomnography is the reference standard for sleep apnoea recording. Treatment modalities include mechanical [continuous positive airway pressure (CPAP), oral appliances], surgical, pharmacological and 'conservative' lifestyle modifications. Finally, Nordic accreditation guidelines for sleep medicine clinics and sleep medicine specialists are described. CONCLUSION: The diagnosis of OSAS should be performed with a polygraph, and the first-line treatment of moderate to severe OSAS is CPAP. Lastly, compliance for this treatment should be optimised with regular clinical controls. PMID- 20298335 TI - Determination of rickettsial and antinuclear antibodies in Danish patients with sarcoidosis. AB - INTRODUCTION: Rickettsia helvetica has been proposed as an aetiological agent in sarcoidosis. OBJECTIVES: To assess the prevalence of plasma anti-Rickettsia antibodies in a Danish population of patients with sarcoidosis and control subjects. In addition, we evaluated the presence of plasma antinuclear antibodies (ANAs). METHODS: Plasma samples from 49 consecutive patients (27 male, 22 female, median age 38 years, interquartile range 32-51 years) were compared with plasma from 51 age- and sex-matched controls (28 male, 23 female, median age 40 years, interquartile range 33-49 years), using a commercially available immunofluorescence assay testing for antibodies towards spotted fever group and typhus group Rickettsia as well as an assay for ANA. We obtained information regarding tick exposure and sarcoid disease manifestations from the medical records. RESULTS: The prevalence of antibodies to Rickettsia in patients with sarcoidosis 1/49 (2%) was not significantly different from the prevalence in the controls 4/51 (8%). The prevalence of ANA was 2/49 (4%) in the patients and 3/51 (6%) in the controls. CONCLUSIONS: The results do not support the hypothesis that Rickettsia or ANAs should be involved in the pathogenesis of sarcoidosis. Seventy one per cent of the patients were under treatment with prednisolone in the 3 months leading up to the blood sample. We assume that antibody-related serological methods for various reasons could be inadequate to diagnose a chronic rickettsial infection. PMID- 20298336 TI - Predicting inadequate spirometry technique and the use of FEV1/FEV3 as an alternative to FEV1/FVC for patients with mild cognitive impairment. AB - INTRODUCTION AND OBJECTIVES: Some patients cannot perform forced vital capacity (FVC). We conducted a study to answer three questions: Can the ability to perform components of spirometry be predicted by the Mini Mental State Examination (MMSE)? What proportion of subjects can perform forced expiratory volume in 3 s (FEV3) but not FVC? Does the forced expiratory volume in 1 s (FEV1)/FEV3 ratio concord with FEV1/FVC ratio in patients with airflow obstruction? METHODS: We conducted a prospective observational study of 267 patients with a mean age of 79 years, including subjects with indicators of frailty. They performed spirometry and the MMSE. Spirometric recordings were compared to the American Thoracic Society 1994 criteria. RESULTS: FVC was achieved by 51% of patients. Inability to perform FVC was predicted by an MMSE < 24 (specificity 94%, sensitivity of 51%). An FEV1/FEV3 ratio < 80% matched a FEV1/FVC ratio < 70% (sensitivity 96%, specificity 97%). Twenty-five percent of subjects were able to reach FEV3 but not FVC; 14% of that group had an MMSE < 24. Subjects with an MMSE < 20 were unable reliably to perform any spirometry. CONCLUSION: Patients with an MMSE < 24 are usually unable to reach FVC reliably when tested on a single occasion, but some can reach FEV3. Patients with MMSE < 20 cannot do spirometry. An FEV1/FEV3 ratio < 80% can be used to help identify patients with airflow obstruction if they are unable to perform full spirometry to FVC. PMID- 20298337 TI - COPD 'diagnosis' based on spirometric reference equations. AB - INTRODUCTION: Chronic obstructive pulmonary disease (COPD) is suspected if the ratio between forced expired volume in 1 s (FEV(1)) and forced vital capacity is below 0.7 after bronchodilatation, according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD). As this ratio varies with age and gender, the lower limit of normality (LLN) of appropriate reference equations appears more adequate. OBJECTIVES: To study the prevalences of suspected COPD according to the GOLD criterion and various reference equations in a well-defined population sample. METHODS: Spirometries obtained in a random population sample of 598 men, 50 or 60 years of age, were analysed. The prevalences of suspected COPD were calculated according to the GOLD criterion and the LLNs of four Nordic and two European reference equations. RESULTS: The GOLD criterion resulted in prevalences of COPD of 9.3% and 23.7% in the 50- and 60-year-old never-smokers, respectively. Depending on the reference equation, the calculated prevalences of COPD varied between 9.3% and 23.4% and 12.0% and 39.1% among all of the 50- and 60-year-old men, respectively. CONCLUSIONS: The GOLD criterion is inadequate because of substantial overestimation in 60-year-old never-smokers. LLNs of the various reference equations are unreliable because of obvious lack of consistency. Spirometric criteria for airway obstruction, and suspicion of COPD, therefore need to be revised. PMID- 20298338 TI - Clinical and functional outcomes in Middle Eastern patients with idiopathic pulmonary fibrosis. AB - BACKGROUND: Baseline clinical and physiological variables have been described as relevant predictors of survival among patients with idiopathic pulmonary fibrosis (IPF). However, substantial heterogeneity in both survival time and mortality has been observed with many of these predictive factors. The incidence and mortality rates of IPF vary from country to country, with race potentially contributing to such variations. OBJECTIVE: We sought to describe baseline clinical features to determine their predictive value among Middle Eastern patients diagnosed with IPF. METHODS: We retrospectively examined 61 patients diagnosed with IPF at a university hospital in Riyadh, Saudi Arabia. RESULTS: At presentation, most patients exhibited either dyspnea or cough. The median survival time for all patients was 92 months. Diminished survival was significantly associated with finger clubbing (P = 0.01). Factors not influencing survival were age, gender, percent predicted forced vital capacity, percent predicted forced expiratory volume in 1 s, percent predicted total lung capacity, percent predicted diffusion capacity of the lung for carbon monoxide and resting oxygen saturation. CONCLUSIONS: Finger clubbing is a significant predictive variable and was associated with a 5-fold increase in mortality. Other baseline demographic characteristics as well as pulmonary function tests were not predictive of prognosis in Middle Eastern patients with IPF. It appears that IPF patients of Middle Eastern descent have a longer median survival curve compared to other races. PMID- 20298339 TI - Immunophenotyping and remodeling process in small airways of idiopathic interstitial pneumonias: functional and prognostic significance. AB - BACKGROUND AND AIMS: To test whether different degrees of immunologic and fibrotic airway remodeling processes occur in idiopathic interstitial pneumonias (IIPs), with impact on functional tests and survival, we studied the collagen/elastic system and immune cell density in the bronchiolar interstitium of lungs with the major types of IIPs. MATERIALS AND METHODS: Histochemistry, immunohistochemistry and morphometric analysis were used to evaluate collagen/elastic fibers and immune cells in the bronchiolar interstitium of open lung biopsies of patients with cryptogenic organizing pneumonia [COP/organizing pneumonia (OP) = 10], acute interstitial pneumonia [AIP/diffuse alveolar damage (DAD) = 20], nonspecific interstitial pneumonia (NSIP/NSIP = 20) and idiopathic pulmonary fibrosis/usual interstitial pneumonia (UIP) = 20. RESULTS: OP lungs presented a significant increase in collagenous/elastic fibers and in the total density of immune cells in the bronchiolar interstitium compared to controls, DAD, NSIP and UIP. We observed a significant increase in CD4, CD8 and CD20 lymphocytes, as well as in neutrophils, macrophages and plasma cells in OP. The increased amount of elastic fibers in the bronchiolar interstitium from OP lungs has a direct association with forced vital capacity (FVC) (r(s) = 0.99, P = 0.03). The most important survival predictor was CD20+ lymphocytes in the bronchiolar interstitium. In decreasing order, patients with UIP [Odds Ratio (OR) = 35.01], high forced expiratory volume in 1 s (FEV(1))/FVC FVC (OR = 7.01), increased CD20+ lymphocytes (OR = 4.44) and collagenous/elastic fiber densities (OR = 2.03 and OR = 1.49, respectively) in the bronchiolar interstitium were those who had the greatest risk of death, followed by those with AIP, NSIP and COP. CONCLUSION: Different degrees of immunologic and fibroelastotic airway remodeling processes occur in the major types of IIPs with impact on physiological tests and survival. PMID- 20298340 TI - A case of obstructive sleep apnea syndrome: unusual comorbidity. AB - INTRODUCTION: Launois-Bensaude syndrome (LBS) is a rare disease, characterized by the accumulation of fatty tissue predominantly in the neck, shoulders and thorax, whose diagnostic is clinical. OBJECTIVES: We describe a new case in a 73 year-old man. As the patient was obese, complained of snoring and was treated for hypertension, we looked for a morbid association with an obstructive sleep apnea syndrome (OSAS). METHODS: A polysomnography (PSG) and a cervical magnetic resonance imaging (MRI) were performed. RESULTS: PSG demonstrated OSAS with an apnea-hypopnea index of 43/h. Cervical MRI showed fatty infiltration resulting in airway narrowing at the pharyngeal but not at the tracheal level. Only, 3 cases of such a morbid association have already been published; in 2 of these patients was a tracheal compression. More over a metabolic syndrome was present. CONCLUSIONS: This observation draws attention to the need for seeking OSAS among patients affected by LBS, even in a moderate form, and emphasises the roles of the upper airway narrowing by the fat infiltration as well as the role of the metabolic syndrome in the genesis of OSAS. PMID- 20298341 TI - Decreased oxygen saturation as a result of haemoglobin Titusville. AB - INTRODUCTION: Our patient was admitted to the hospital due to shortness of breath. Although partial pressure of oxygen in arterial blood was normal, oxygen saturation measured with pulse oximetry (SpO(2)) was markedly decreased. SpO(2) and oxygen saturation of arterial blood (SaO(2)) stayed low during monitoring even with an increased fraction of oxygen in inspired air. METHODS: Report of a case. RESULTS: After extensive investigations, a rare haemoglobin variant, haemoglobin Titusville, with decreased oxygen binding capacity was discovered. This is the first haemoglobin Titusville case reported in Scandinavian countries. PMID- 20298342 TI - Chronic necrotizing and allergic bronchopulmonary aspergillosis in an asthmatic patient--a therapeutic challenge. PMID- 20298343 TI - Inhaled corticosteroids in children: use and effects of early treatment on asthma and lung function. Prevalence of asthma and the impact of severity in early life on later asthma in childhood. AB - INTRODUCTION: The role of inhaled corticosteroids (ICS) on disease progression in asthmatic children is not yet clear. AIMS: This study was conducted (i) to determine how often ICS were used for treatment of obstructive airways disease (OAD) in early childhood; (ii) to assess if ICS treatment had an effect on lung function in young children with recurrent bronchial obstruction (rBO); (iii) to explore if early ICS treatment in children with OAD during the first 2 years of life can modify occurrence of current asthma in school children; (iv) to define a severity score for severity of OAD during the first 2 years of life and assess if the severity score can be used to predict asthma in school children; and (v) to investigate the prevalence of asthma in children in an urban population. SUBJECTS AND METHODS: The present study is part of a 10-year follow-up of children in the prospective birth cohort (n = 3754), the Environment and Childhood Asthma study in Oslo. For aim 1, all children from the entire cohort who had completed follow up questionnaires as well as all children defined with rBO were assessed. For aim 2, 54 children with rBO (with and without ICS treatment) and 15 controls with tidal flow volume measurements upon presentation of the disease and 2 years of age were studied. For aims 3 and 4, 459 subjects (with and without rBO at 2 years of age) from the case control study who attended 10-year follow-up were studied. For aim 5, the 616 of 803 subjects who had lung function measurements performed after birth were reinvestigated at the age of 10 years. RESULTS: A total of 2.1% of all the children in the cohort and 21% of children with rBO had received ICS treatment by 2 years of age. The mean difference of change in baseline tidal breathing (the ratio of time to peak expiratory flow to total expiratory time) was significantly higher in the ICS-treated group only by 2 years of age and correlated significantly with duration of ICS treatment. However, in rBO children, the use of ICS treatment before 2 years of age was not associated with reduced risk of current asthma at 10 years of age. The risk (odds ratio, 95% confidence interval) of current asthma among rBO subjects with a severity score above five was 20.2, 9.9-41.3 compared to controls. In 10-year-old children, the lifetime prevalence of asthma was 20.2%. CONCLUSIONS: One-fifth of young children with recurrent bronchial obstruction had received inhaled corticosteroids by age 2 years. Lung function appeared to improve in children using ICS from the start of symptoms of OAD until 2 years of age, mostly in children with the longest duration of treatment. However, use of ICS during the first 2 years of life in children with OAD did not reduce asthma present 8 years later. A scoring system based on severity and frequency of OAD during the first 2 years of life predicted current asthma at 10 years of age. One in five 10-year-old children in the city of Oslo at some time had asthma. PMID- 20298344 TI - Introduction (why epidemiologic research?). PMID- 20298345 TI - General population-based cohorts for studies of lung health in adults in Sweden. AB - Epidemiological population-based studies about lung health in Sweden have mostly been focused on obstructive airway diseases. From the 1960s to the 1980s, the epidemiological studies were cross-sectional, aiming at the study of the prevalence of asthma, chronic bronchitis and respiratory symptoms and their associations with mainly demographic data. With the exception of highly stratified samples, for instance the men born on 1913 in Gothenburg and cohorts of occupational groups or work places, general population-based cohorts for studies of lung health in adults are still not very common. Two large-scale studies of lung health have been in progress in Sweden for more than 20 years; the Obstructive Lung Disease in Northern Sweden (OLIN) Studies, which started in 1985, and the Swedish part of European Community Respiratory Health Survey (ECRHS) since 1989 with the follow-up survey labelled Respiratory Health in Northern Europe (RHINE). During the 1990s the comparative studies between Finland, Estonia and Sweden (The FinEsS Studies) started. These and other studies will be reviewed in the following exemplifying change of aims and study designs over time as well as change of focus of risk factors under study. PMID- 20298346 TI - Norwegian population surveys on respiratory health in adults: objectives, design, methods, quality controls and response rates. AB - BACKGROUND AND AIMS: Quantifying the prevalence of asthma, chronic obstructive pulmonary disease (COPD) and restrictive pulmonary diseases in Norway is needed to document the burden of chronic respiratory inflammatory diseases on disability, health care costs and impaired quality of life. To introduce effective interventions for prevention, cure and care, there is a prerequisite to know the environmental causes. Furthermore, using relevant and precise phenotypes from community-based studies are important for detecting molecular-genetic causes for diseases. METHODS: The Norwegian Population Survey Initiative on Respiratory Health in Adults has, for four decades, applied international standardised methods for the recording of respiratory symptoms, health status, exposure to risk factors, socio-economic factors and the use of health services. Measurements of spirometry, metacholine bronchial responsiveness, transfer factor for carbon monoxide, atopy as well as chest X-ray examinations have been used advocating the internationally accepted methods. All surveys had similar quality controls, supervision and training of the field-worker team. RESULTS: From 1965 to 1999, random population samples, altogether including 178 690 individuals, have been invited by random sampling to seven surveys on respiratory health in the counties of Oslo (39 998 people) and Hordaland (138 692 people). The surveys were initiated in 1964, 1972, 1985, 1988, 1991 and two in 1998. The age span of those invited persons varied from 15 to 74 years at baseline. It included 43 330 women and 135 537 men. Altogether 130 075 (73%) persons participated by returning an answered questionnaire. Spirometry results are available from 41 335 persons at baseline. A biobank for DNA and blood markers has been established. Data from longitudinally clinical-epidemiological studies were available by 2007, for three surveys after 20 years, 10 years and 6-7 years, and also for parts of three other surveys, while one survey has been examined for cause-specific mortality after 30 years. The response rates of the baseline studies varied from 90% to 68% of those invited and, in general, it has declined over 35 years. The response rate of the longitudinal studies with follow-ups also declined with time after the baseline study. CONCLUSIONS: Great challenges for future population-based studies are (i) to keep the participation rates high in community studies; (ii) to standardise the basic clinical-epidemiological methods over decades of follow-up and to systematically transfer these methods into new populations with different languages and cultures and (iii) to focus on important research questions on respiratory health for the community. PMID- 20298347 TI - The Obstructive Lung Disease in Northern Sweden (OLIN) longitudinal paediatric study I--the first 10 years. AB - BACKGROUND: Prospective studies of asthma and allergic conditions based on the general population are scarce. AIM: To summarize the methods and main results from a prospective study among school children. METHODS: In 1996, a cohort of 3525 children aged 7/8 years in Northern Sweden were invited to a questionnaire survey using an expanded ISAAC protocol, and 97% participated. The cohort has been followed up yearly with high participation rate. Skin prick tests were conducted 1996, 2000 and 2006/2007. Allergens in dust from homes and schools have been analyzed. Sub samples have participated in interviews, lung function tests, bronchial hyper reactivity test, and analyses of IgE and IgG antibodies in serum. RESULTS: The prevalence of asthma was 6% at age 7-8 years and increased by age. The incidence of physician-diagnosed asthma after the age of 7-8 years was around 1/100/year. The prevalence of positive skin prick test increased from 21% at age 7-8 to 30% at age 11-12 years. Remission of allergic sensitization was rare, while asthma remission was 5% yearly. The main risk factor for asthma and allergic sensitization increased in importance with increasing age. Allergic and non-allergic asthma had different risk factor pattern. Environmental risk factors decreased in impact after the age of 7. Avoidance of pets at home did not protect from asthma or allergic sensitization. CONCLUSION: The study includes important sources of data for further longitudinal analyses that will contribute to the understanding of the development and the nature of asthma and allergic sensitization. PMID- 20298348 TI - What has the ECRHS told us about the childhood risks of asthma, allergy and lung function? AB - Few studies investigate how environmental factors in childhood may influence adult respiratory health. The European Community Respiratory Health Survey (ECRHS) is a longitudinal multi-centre study of Western world adults, including retrospective assessment of early life factors. Analyses of the ECRHS showed both beneficial and harmful long-term effects of childhood factors on adult asthma, allergy and lung function. Childhood pets were associated with less adult atopy and hay fever; beneficial effects were also indicated for growing up on a farm and for early exposure to other children. The findings have contributed to further development of the hygiene hypothesis and further understanding of the mechanisms relating microbial stimulation to allergy; however, the public health consequences may be limited. Harmful effects of early life factors on adult asthma and lung function were indicated for severe respiratory infections early in life, parental smoking and long-term dog keeping. Intervention with regard to parental smoking and vaccination against common lower airways infections may improve respiratory health in the population. Thus, early life environment had permanent beneficial and adverse effects on adult respiratory health. The multi centre structure of the ECRHS, the large sample size, the extensive information about each participant and follow-up until the age of 56 years, have given the basis for convincing conclusions, and made possible publication of unsuspected findings in spite of the problems related to adult recall of childhood events. The ECRHS have contributed substantially to increased knowledge about the early life origins of allergy and obstructive pulmonary disease, providing a basis for prevention. PMID- 20298349 TI - What can we learn about asthma and allergy from the follow-up of the RHINE and the ECRHS studies? AB - OBJECT: The international population-based studies RHINE and ECRHS have provided new insight in the epidemiology and management of asthma, allergy and rhinitis in young adults. The aim of the present review is to focus on longitudinal results with regard incidence and net change of asthma and asthma-like symptoms, risk factors and management of asthma, with special reference to the Nordic-Baltic countries. RESULTS: Asthma and rhinitis are common conditions that are important in a public health perspective. There are gender differences in incidence and remission. A socio-economic gradient that non-atopic asthma is more strongly related to poverty seems to have developed in the last decade. These findings will challenge our welfare states in the future. In addition, occupational, as well as indoor and outdoor environmental exposures, influenced the onset of asthma. The population-attributable risk for adult asthma because of occupational exposures is equivalent to an incidence of new-onset asthma of 250-300 cases per million per year. Genetic factors, allergic sensitisation, gastro-oesophageal reflux, habitual snoring, diet and other factors may also contribute to the onset of asthma and rhinitis. Even though management of asthma has improved, there are still great variations throughout Europe. These findings highlight the key role doctors and nurses play in educating and reviewing management of patients. PMID- 20298350 TI - Association between respiratory symptom score and 30-year cause-specific mortality and lung cancer incidence. AB - INTRODUCTION: Respiratory symptoms are among the main reasons why patients make contact with healthcare professionals and they are associated with several diseases. OBJECTIVE: The aim of this study was to investigate the relationship between respiratory symptoms reported at one time and 30 years cause-specific mortality and incidence of lung cancer in an urban Norwegian population. MATERIALS AND METHODS: A total of 19 998 men and women, aged 15-70 years, were in 1972 selected from the general population of Oslo. They received a postal respiratory questionnaire (response rate 89%). All were followed for 30 years for end-point mortality and for lung cancer. The association between respiratory symptoms, given as a symptom load, and end point of interest were investigated separately for men and women by multivariable analyses, with adjustment for age, occupational exposure to air pollution and smoking habits. RESULTS: A total of 6710 individuals died during follow-up. Obstructive lung diseases (OLDs) and pneumonia accounted for 250 and 293 of the total deaths, respectively. Ischaemic heart disease (IHD) accounted for 1572; stroke accounted for 653 of all deaths. Lung cancer developed in 352 persons during follow-up. The adjusted hazard ratio for mortality from OLD and pneumonia, IHD and stroke increased in a dose-response manner with symptom score, more strongly for OLD and IHD than for pneumonia and stroke. CONCLUSIONS: Respiratory symptoms were positively associated with mortality from OLD, pneumonia, IHD and stroke, and incidence of lung cancer. This association was significant for mortality from OLD and IHD. PMID- 20298351 TI - COPD and co-morbidities, with special emphasis on cardiovascular conditions. AB - The concept of COPD as a systemic disease has been widely accepted in the past several years. In parallel, it has been emphasised that COPD morbidity and mortality is strongly related to co-morbid conditions. This review summarises some recent studies showing that in patients with COPD, the prevalence of cardiac failure is manifested in 10%-46% of the patients, and that up to 40% of patients with cardiac failure show evidence of COPD, about half of them not earlier diagnosed. Recent data also show an increased risk for arteriosclerotic manifestations in COPD patients, and cardiac complications are common causes of death in COPD patients. Other manifestations of the metabolic syndrome, as diabetes, are also over-represented in patients. It is also a well-established fact that a low FEV(1) is a risk factor for cardiovascular diseases and events. Mechanistically, a systemic inflammation in COPD could be a link to cardiovascular events. COPD raises inflammatory parameters and local anti inflammatory treatment seems to have a potential to decrease the systemic inflammation and also to decrease cardiovascular events. PMID- 20298352 TI - The Obstructive Lung Disease in Northern Sweden Chronic Obstructive Pulmonary Disease Study: design, the first year participation and mortality. AB - BACKGROUND: Most epidemiological data on chronic obstructive pulmonary disease (COPD) are cross-sectional, and the longitudinal course of disease on population bases is incompletely described. AIM: To describe an epidemiological study designed to follow the longitudinal course of disease in chronic obstructive lung disease, COPD, including co-morbidity and mortality and further, to evaluate the impact of COPD on quality of life and health economics. MATERIALS AND METHODS: From the Obstructive Lung Disease in Northern Sweden studies database cohorts I IV, all subjects with COPD according to the Global Initiative for Chronic Obstructive Lung Disease spirometric criteria, FEV(1)/FVC < 0.70 (n = 993), were identified together with a similar size age- and gender-matched control group. The study population was invited to a yearly examination starting in year 2005. The examinations included structured interview, spirometry with reversibility testing, oxygen saturation and health-related quality of life questionnaires. RESULTS: On the first year, 83% of the population was examined, and the subjects unable to attend the examination were interviewed by telephone. Altogether, 91% of the original study population participated (95% of all subjects were alive at the end of the first year). Mortality was significantly higher among subjects with COPD, 5.1%, compared with controls, 3.0% (P = 0.018). CONCLUSION: The study design including cases of COPD representative of COPD by disease severity in the general population and a similar sized control group, together with a high participation rate in the first study year, creates excellent conditions for evaluating the impact of COPD on population bases, and to follow the longitudinal course of disease in COPD. PMID- 20298353 TI - Designing studies for diagnostic tests. AB - BACKGROUND AND AIMS: Requirements for diagnostic tests include high validity and good repeatability. METHODS AND RESULTS: The validity of a test refers to what extent the test measures what it is supposed to measure and is often expressed in terms of sensitivity and specificity. A graph may be constructed to incorporate both the sensitivity and specificity of a given test, the receiver operator characteristic (ROC) curve. The ROC curve actually compares the true positive fraction (sensitivity) vs the false positive fraction for a series of cut-off points for a given test. Use of the curve requires that the diagnostic test and the gold standard must be independent of each other. Repeatability is the ability of a test to give the same results in repeated measurements. CONCLUSION: When designing a study to examine a diagnostic test, the following principles should be followed. First, the order of performance of the diagnostic test and the gold standard in repeated measurements should be randomised. Second, in repeated measurements, the test situations should be equal. Third, the technicians performing the tests should be blinded to the data obtained in the other test or to the result of the gold standard. A pilot study is recommended before conducting the study to examine the diagnostic test. PMID- 20298354 TI - Is CT a new research tool for COPD? AB - INTRODUCTION: Chronic obstructive pulmonary disease (COPD) is composed of two diseases: chronic bronchitis and emphysema. METHODS AND RESULTS FOR EMPHYSEMA: The essence of emphysema is loss of alveolar walls. Computed tomography (CT), which is based on the attenuation of x-rays, provides precise anatomical information on the density of tissues. Therefore, CT, especially HRCT, is the in vivo method of choice for detection and quantification of emphysema. Reduction of radiation dose has little influence on lung density measurements. This opens up opportunities for CT as a screen for emphysema. Furthermore, repeat scans can be used to follow the progress of emphysema. The depth of inspiration is an important source of variation of lung density measurements, but inspiratory level has no influence on the total weight of the lung derived from CT scans, making it easy to adjust lung densities to a standardised volume such as predicted Total Lung Capacity (TLC) by the following formula: adjusted lung density = observed lung density x observed TLC/predicted TLC. METHODS AND RESULTS FOR CHRONIC BRONCHITIS: Chronic bronchitis represents the airway component of COPD. During recent years, improved resolution of HRCT with faster scans, smaller detectors and multi-detector-row technology has made it possible to visualise airways down to a range of 2 mm diameter (6th generation), which represents the upper-size limit of the pathophysiologically important 'small airways'. CONCLUSION: In the future, CT may replace pulmonary function measurements (FEV(1)) as the gold standard for assessing the response to treatment in clinical trials of COPD, provided that the lung community does the same painstaking work of standardising and validating CT that it did for spirometry. PMID- 20298355 TI - Inflammatory markers in COPD. AB - Chronic obstructive pulmonary disease (COPD) is identified as an inflammatory disorder characterised by airway and lung inflammation and destruction with systemic involvement of multiple organ systems. The inflammatory reaction could be monitored not only in the airways by the use of bronchoalveolar lavage (BAL), sputum, exhaled air, and exhaled breath condensate but also in blood and urine as well as in tissue obtained at surgery or autopsy. There is a large number of cytokines, chemoattractants and other mediators that are of importance for the interplay of inflammatory mechanisms in COPD. Neutrophilic granulocytes are key players in the inflammatory reaction and the most important chemoattractants for these cells seem to be IL-8 (CXCL8) and leukotriene B(4) (LTB(4)). Also, the macrophages and chemoattractants for mononuclear cells (CCL2, CCL3) are of importance as are T-lymphocytes, predominantly of the cytotoxic subtype (CD8+). Analyses in exhaled breath condensates and exhaled air have not been tremendously encouraging but there is a clear space for further development in this field within the near future. Blood markers, such as IL-6, CRP, and fibrinogen, have attracted interest during recent years, and further studies in this area will probably increase the understanding of systemic manifestations in COPD, in particular, regarding co-morbidity with cardiovascular disease. PMID- 20298356 TI - Phenotypes of obstructive lung disease. AB - Recently, there has been much emphasis on the fact that there are many different phenotypes in asthma and chronic obstructive pulmonary disease (COPD). The aim of this review is to investigate some aspects of phenotyping in these two diseases. Epidemiological studies show a quite different risk factor pattern in allergic and non-allergic asthma. Several studies also indicated that there are pathophysiological differences between these two types of asthma: such as eosinophil inflammation in allergic and neutrophil predominance in non-allergic asthma. Neutrophil inflammation may also be a marker of severe asthma. At least one study indicates that non-allergic asthmatics are less responsive to inhaled corticosteroids than allergic asthmatics. Recently, it has been emphasized that COPD also has manifestations other than lung function decline and that this also needs to be taken into account in severity characterisation. Dyspnea, weight loss, psychological status and co-morbidity are factors that seem to be of large prognostic importance independently of the level of airflow obstruction in COPD. Progress has been made in understanding how asthma develops, but effective measures for primary prevention is still lacking. Better phenotyping in asthma will hopefully enable us to make progress in this area. Phenotyping is also important for assessment of prognosis in both asthma and COPD. PMID- 20298357 TI - Attributable fractions for partitioning risk and evaluating disease prevention: a practical guide. AB - INTRODUCTION: The attributable fraction (AF) is used for quantifying the fraction of diseased ascribable to one or more exposures. The methodology and software for its estimation has undergone a considerable development during the last decades. OBJECTIVES: To introduce methods for: (i) apportioning excess risk to multiple exposures, groups of exposures and subpopulations; (ii) graphical description; and (iii) survival data. RESULTS: Adjusted, sequential and average AFs are reasonable measures obtainable with standard software. The latter two both sum up to the combined AF for a set of exposures. The average AFs are independent of the exposures' ordering. For an ordered, preventive strategy, scaled sample space cubes illustrate the effects on the risk of disease from stepwise exposure removal. Pie charts illustrate the portions of the total risk ascribed to different exposures or risk-profiles. Attributable hazard fraction, AF before time t, and AF within study incorporate time to disease and interventions. CONCLUSIONS: The practice of crude calculations of AFs in epidemiology should be abandoned. Further development of methods for AFs with survival data and possibly linking it to causal modelling is of interest. PMID- 20298358 TI - Economics of COPD: literature review and experiences from field work. AB - INTRODUCTION: The burden of diseases should be described in terms of costs. The available literature gives imprecise estimates of costs of chronic obstructive pulmonary disease (COPD) in the Nordic populations. Previous studies have methodological weaknesses related to choice of disease criteria, the use of highly selected populations and insufficient specification of the cost process. There are no robust estimates concerning the economics of COPD in Norway. METHODS: We have conducted a 1 year follow-up cost of illness study in a general population, recruiting ever-smoking Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage 2+ COPD patients and ever-smokers without COPD. We have used diaries to recollect data, and comprehensive questionnaires to cover all costs of COPD. RESULTS: The main challenges were the participants' unwillingness to complete diaries, the large amount of information and the logistics related to following up 476 individuals on four occasions during one year. CONCLUSIONS: We doubt the effect of diaries. However, we recommend a detailed planning of logistics and to emphasize main cost drivers. PMID- 20298359 TI - Hormonal factors and respiratory health in women--a review. AB - Sex hormones appear to play an important role in the lung health of women. This is, however, poorly understood and, in most aspects, poorly investigated; and the literature has been contradictory and confusing. This review presents recent research concerning the involvement of sex hormones in respiratory health of adult women, using the population surveys European Community Respiratory Health Survey and Respiratory Health in Northern Europe. Respiratory health varied substantially according to hormonal and metabolic conditions. First, menopause was associated with lower lung function and more respiratory symptoms, especially among lean women. Second, hormonal replacement therapy (HRT) was associated with increased risk for asthma and wheeze; also, this association was particularly strong among lean women. Third, women with irregular menstruations in fertile age had more asthma, particularly allergic asthma, and reduced lung function, independently of body mass index (BMI) and physical activity. The findings were consistent across cultural and geographical borders. Our studies revealed that considering interplay between hormonal and metabolic factors is a clue to understand the effects of female sex hormones on the airways. A BMI of around 24 25 kg/m(2) appeared to be optimal; women with this BMI had no increase in respiratory health problems when reaching menopause or using HRT, and women in fertile age with this BMI had optimal lung function independently of menstrual status. In conclusion, female sex hormones appear to play a most important role for lung health in women. Further research on effects of sex hormones on the airways should take into account potential interplay with metabolic factors. PMID- 20298360 TI - Concomitant obstructive sleep apnea and chronic obstructive pulmonary disease: study design--the OLIN OSAS-COPD study. AB - BACKGROUND: Obstructive sleep apnea (OSA) and chronic obstructive pulmonary disease (COPD) are both common disorders. Concomitant disease, overlap syndrome, is reported to cause a more severe condition. AIM: To describe a study designed to evaluate the prevalence of overlap syndrome in the general population, and further, to assess the impact of overlap syndrome on cardiovascular morbidity and health-related quality of life. A secondary aim is to evaluate screening oxygen saturation (Sa02) by pulse oxymetry. MATERIAL AND METHOD: From the last examination of the OLIN-studies (Obstructive Lung Disease in Northern Sweden), cohorts I-IV all subjects with FEV1 < or = 50 percent predicted or Sa02 < or = 93 percent predicted were identified (Phase 1). They are invited to a program including lab tests, spirometry, arterial blood gases, chest x-ray, echocardiography, sleep studies and health-related quality of life (HRQL) questionnaires. In Phase 2, a random sample of subjects reporting snoring as a problem (n = 100) will be invited to a limited program above all including sleep studies and HRQL questionnaires; and in Phase 3, a random sample (n = 100) will be invited to a similar program. SUMMARY: The collection of data in Phase 1 is in progress and will be completed by the end of year 2007. Phase 2 will start year 2008. PMID- 20298361 TI - Asthma in school age: prevalence and risk factors by time and by age. AB - BACKGROUND: Childhood is the most important age for asthma development. Recent reports indicate that the prevalence of asthma in children has plateaued after having increased for decades. AIMS: To study prevalence and risk factor patterns of asthma by age and by time. METHODS: In 1996, all children in grade 1-2 (age 7 8) in three cities in Northern Sweden were invited to an expanded International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire. A total of 3430 children (97%) participated yearly until 2000 (age 11-12). A subset (n = 2454) was invited to skin-prick testing in 1996 and 2000 with 88% and 90% participation. In 2006, another cohort (n = 2704) was identified and studied by identical methods with 96% participation. A total of 1700 children (90% of invited) were skin-prick tested. RESULTS AND COMMENTS: From age 7-8 to 11-12, the prevalence of physician-diagnosed asthma increased, 5.7%-7.7% (P < 0.01) while current wheeze decreased, 11.7%-9.4% (P < 0.01), indicating a less diverse spectrum of symptoms with age. The yearly remission from asthma was 10% (lasting remission 5%), largely determined by allergic sensitisation. Allergic sensitisation (OR 5) and a family history of asthma (OR 3) were important risk factors for asthma at age 7-8 and 11-12. However, several other significant risk factors at age 7-8 (low birth weight, respiratory infections and house dampness) lost importance until age 11-12. Maternal and paternal asthma were equally important risk factors (OR 3-4) at age 7-8. Sibling asthma was only a marker of parental disease. FUTURE PERSPECTIVES: Through comparison with the 2006 cohort, trends in prevalence and in risk factors from 1996 to 2006 will be studied. PMID- 20298362 TI - FinEsS-Stockholm and the Stockholm adult asthma study. AB - Two major studies on asthma and respiratory symptoms are presently in progress in Stockholm. The FinEsS-studies has been ongoing since 1996, with a follow-up study preformed in 2006 and a new cohort selected in 2007. The FinEsS studies focus on prevalence and incidence of asthma and respiratory symptoms in a general population. Clinical follow-up surveys will also target COPD. Further aims include remission and relapse of disease and symptoms and their determinants. The Stockholm adult Asthma Study (SaAS) began in the spring of 2007 and data is being collected presently. The SaAS study focus on the medical care and medication given to asthmatics in Stockholm, and the study population consists of asthmatics found in the two Swedish cohort studies. PMID- 20298363 TI - Genetics of chronic obstructive pulmonary disease: a case-control study in Bergen, Norway. AB - AIMS: Chronic obstructive pulmonary disease (COPD) is a complex disease influenced by multiple genetic and environmental factors. This short communication gives a description of the preliminary genetic results from a case control study in Bergen, Norway. METHODS: A large case-control study in Bergen in 2003-2005 with 6365 invited subjects generated 1954 cases or controls. The overall attendance of invited subjects was 60%, but causes of non-attendance varied considerably among different sources of recruitment. RESULTS: In this case control study, the candidate gene SERPINE2 on chromosome 2q has demonstrated significant association to COPD. However, only weak or lacking associations have so far been observed for the other candidate genes examined. CONCLUSION: These findings provide support for SERPINE2 as a COPD susceptibility gene in the Norwegian population. PMID- 20298364 TI - Asthma genes revisited. PMID- 20298365 TI - Overview on the current status of asthma genetics. AB - INTRODUCTION: Asthma is a complex heterogeneous and mutifactorial disease occurring at the interface of multiple genes that interact with various environmental stimuli insulting the immune system at different levels and different times of disease susceptibility. OBJECTIVE: The present paper is a review of the current status of the genetics of asthma. RESULTS: Sequence variants in hundreds of genes have been associated with asthma using both family based and case control screening methods. CONCLUSION: As the number of genes known to be associated with asthma risk is rapidly growing, it is essential to begin integrating epidemiologic, genetic and genomic strategies to unravel the relationships between genotype and phenotype, and elucidate the pathogenesis of asthma with the goal to make clinical use of these discoveries. PMID- 20298366 TI - Tracheostomy tube manometry: evaluation of speaking valves, capping and need for downsizing. AB - INTRODUCTION: Readiness to speak is a major problem for many tracheostomized patients. Evaluation for tracheostomy tube capping or speaking valve is often subjective. OBJECTIVES: We first wanted to assess whether there were differences among speaking valves. We developed a care pathway for tracheostomy tube evaluation and management including manometry, which we wanted to evaluate. METHODS: Three different speaking valves were assessed using manometry and measuring dyspnea in 21 patients. Subsequently, 100 consecutive patients referred for tracheostomy tube evaluation in a long-term acute-care rehabilitation hospital were studied using our care pathway with manometry before and after tracheostomy tube changes. RESULTS: Inspiratory pressures differed among the speaking valves. Borg scale was higher among patients with high expiratory pressures. Of the 100 patients, following our care pathway, speech (speaking valve or capping) was recommended for 78 patients with their initial tube, and for 93 patients within 2 days of their initial evaluation. Tracheostomy tube downsizing was recommended in 94 patients. Downsizing led to significant reductions in airway pressures. Capping was initially recommended for 12 patients and for 71 following downsizing. Women had higher pressures than men for the same size tubes. CONCLUSION: Tracheostomy tube manometry is very helpful in objectively guiding recommendations for speaking valve use, capping, and changing tracheostomy tubes. Speech is an early recommendation for most patients. PMID- 20298367 TI - The extent of emphysema in patients with COPD. AB - BACKGROUND AND AIMS: The global initiative for COPD (GOLD) adopted the degree of airway obstruction as a measure of the severity of the disease. The objective of this study was to apply CT to assess the extent of emphysema in patients with chronic obstructive pulmonary disease (COPD) and relate this extent to the GOLD stage of airway obstruction. MATERIALS AND METHODS: We included 209 patients with COPD. COPD was defined as FEV(1)/FVC < 0.70 and no reversibility to beta(2) agonists. All patients were current smokers with a smoking history of >or=20 pack years. Patients were assessed by lung function measurement and visual and quantitative assessment of CT, from which the relative area of emphysema below 910 Hounsfield units (RA-910) was extracted. RESULTS: Mean RA-910 was 7.4% (n = 5) in patients with GOLD stage I, 17.0% (n = 119) in stage II, 24.2% (n = 79) in stage III and 33.9% (n = 6) in stage IV. Regression analysis showed a change in RA-910 of 7.8% with increasing severity according to GOLD stage (P < 0.001). Combined visual and quantitative assessment of CT showed that 184 patients had radiological evidence of emphysema, whereas 25 patients had no emphysema. CONCLUSION: The extent of emphysema increases with increasing severity of COPD and most patients with COPD have emphysema. Tissue destruction by emphysema is therefore an important determinant of disease severity in COPD. PMID- 20298368 TI - Asthma management and asthma control in Sao Paulo, Brazil and Uppsala, Sweden: a questionnaire-based comparison. AB - BACKGROUND AND AIMS: The Global Initiative Against Asthma (GINA) was developed to meet the global challenge of asthma. GINA has been adopted in most countries and comparison of asthma management in different parts of the world may be of help when assessing the global dissemination of the guideline. The overall goals in GINA include that asthma patients should be free of symptoms, acute asthma attacks and activity limitations. The aim of the present study was to compare asthma management and asthma control in Sao Paulo, Brazil and Uppsala, Sweden. MATERIALS AND METHODS: Information was collected from asthmatics in Sao Paulo and Uppsala with a questionnaire. The questionnaire dealt with the following issues: symptoms, smoking, self-management, hospital visits, effect on school/work and medication. RESULTS: The Sao Paulo patients were more likely to have uncontrolled asthma (36% vs 13%, P < 0.001), having made emergency room visits (57% vs 29%, P < 0.001) and having lost days at school or work because of their asthma (46% vs 28%, P = 0.03) than the asthmatics from Uppsala. There were no difference in the use of inhaled corticosteroids, but the Brazilian patients were more likely to be using theophylline (18% vs 1%, P = 0.001) and less likely to be using long-acting beta-2 agonists (18% vs 37%, P < 0.001). CONCLUSION: We conclude that the level of asthma control was lower among the patients from Sao Paulo than Uppsala. Few of the patients in either city reached the goals set up by GINA. Improved asthma management may therefore lead to health-economic benefits in both locations. PMID- 20298369 TI - Stable bronchiectasis is associated with low serum L-ficolin concentrations. AB - BACKGROUND AND AIMS: Bronchiectasis is a common chronic respiratory condition with recurrent cough and sputum production and recurrent chest infections. It is characterised by pathological dilatation of the bronchi thought to result from infection and inflammation. It was hypothesised that impaired innate immunity might influence susceptibility to this disease process. The aim of the present study was to look for an association between bronchiectasis and insufficiency of either mannan-binding lectin (MBL) or L-ficolin. MATERIALS AND METHODS: MBL and L ficolin were measured by Enzyme-linked Immunosorbent Assay (ELISA) in sera from 119 clinically stable bronchiectasis patients, and compared with 43 age-matched disease controls admitted to hospital with community-acquired pneumonia, as well as healthy blood donors (168 for L-ficolin and 564 for MBL). RESULTS: Average (mean and median) serum L-ficolin concentrations were lower in the bronchiectasis patients (P < 0.04), but average MBL values did not differ significantly between the three groups. Relative L-ficolin deficiency was more frequent in bronchiectasis patients compared with blood donors (P 6000 DNA patterns from TB patients nationwide. RESULTS: Only one single MT DNA pattern matched the DNA profile of the isolate from the nurse. The pattern originated from a patient shortly admitted to the department where she worked at the time. MT transmission had occurred in spite of very short exposure. CONCLUSION: By adding modern molecular epidemiological methods to traditional epidemiological surveys, a more detailed picture of MT transmission pathways can be obtained, showing that MT transmission can occur even after extremely short exposure. This stresses the necessity for adequate respiratory protection among hospital staff taking care of patients with pulmonary symptoms suspected for TB. PMID- 20298374 TI - Medical Assessment Unit staff knowledge and performance of inhaler technique: establishing educational goals. PMID- 20298375 TI - Occult tracheal tumour detected by lung function tests. PMID- 20298376 TI - Airway hyperresponsiveness and airway inflammation in elite swimmers. AB - INTRODUCTION: The prevalence of respiratory symptoms and airway hyperresponsiveness (AHR) is high in elite athletes; swimmers have one of the highest prevalences. No consensus exists on what airway challenge to use when identifying AHR in elite athletes. Further, knowledge is sparse about when during their active sport career AHR develops and if there is an acute effect on the airway inflammation of a swimming training session. OBJECTIVES: We aimed to (i) evaluate the airway response to a methacholine challenge, a eucapnic voluntary hyperpnoea (EVH) test, a field-based exercise test (FBT) and a laboratory-based exercise test (LBT) in adult elite swimmers; (ii) investigate airway responsiveness and airway inflammation in adolescent elite swimmers; and (iii) evaluate the acute effect of a training session in an indoor swimming pool on airway inflammation in adolescent elite swimmers. MATERIALS AND METHODS: Two groups were studied. (i) In adult elite swimmers (n = 16), we examined airway response in four airway provocation tests: methacholine challenge, EVH test, FBT and LBT. (ii) In adolescent elite swimmers (n = 33), we examined airway responsiveness to EVH and methacholine, and airway inflammation and compared the findings with those in asthmatic adolescents (n = 32) and unselected adolescents (n = 35). Further, we examined the acute effect of swimming on airway inflammation in a subpopulation of the adolescent swimmers (n = 21). Airway inflammation was evaluated using sputum induction, measurements of exhaled nitric oxide (FeNO) and exhaled breath condensate (EBC). RESULTS: Of 16 adult swimmers, eight (50%) had AHR; five of the eight (63%) were identified with the EVH test, four (50%) with the FBT, four (50%) with the LBT and none with the methacholine challenge [provocative dose of methacholine causing a 20% fall in FEV1 (PD(20)) or=22 ppb prescribed increase in ICS). Quantitative analyses of serum IgE (eight common aeroallergens) confirmed allergy. RESULTS: At baseline, FE(NO) and the sum of IgE antibody titres for perennial allergens correlated significantly (r = 0.47, P = 0.04). After a step-up in ICS treatment, this correlation had disappeared. Nine patients had persistently elevated FE(NO) at last visit (mean 35 ppb vs 16 ppb). This group was more frequently exposed to relevant allergens or colds (89% vs 27% of patients, P < 0.05) and had higher IgE antibody titres (perennial allergens) compared with the normalised group (mean 28.9 kU/L vs 10.7 kU/L, P < 0.05). CONCLUSION: Serum IgE against perennial allergens and FE(NO) correlate in patients with allergic asthma. However, this relationship disappears after a high dose ICS regimen, suggesting that FE(NO) relates to bronchial inflammation and not IgE levels per se. High degree of IgE sensitisation together with allergen exposure may lead to ICS-resistant airways inflammation. PMID- 20298398 TI - Relationships between hand-rolled cigarettes and primary lung cancer: a Norwegian experience. AB - INTRODUCTION: Detailed smoking history of patients developing lung cancer is rarely known, especially not for users of hand-rolled cigarettes. In Norway, smoking hand-rolled tobacco is still popular, accounting for one-third of the total tobacco consume. METHODS: A questionnaire-based study revealing detailed information about tobacco consume with consecutive inclusion of all persons developing lung cancer in Southern Norway 2002-2005. RESULTS: In this unselected population with 479 patients with newly diagnosed lung cancer, 95% had a smoking history and 88% of ever-smokers had smoked primarily hand-rolled cigarettes. The hand-rolled cigarette smokers had smoked fewer cigarettes daily (15) and less pack-years of tobacco (34) than fabricated cigarette smokers (20, P < 0.0001 and 42, P = 0.021, respectively). Smoking hand-rolled cigarettes was considerably more frequent than expected from official sales statistics. Hand-rolled cigarette smoking revealed an odds ratio of 13 for developing lung cancer compared with smoking fabricated cigarettes. CONCLUSION: In this unselected population with newly diagnosed lung cancer, nine out of 10 ever-smokers had smoked primarily hand-rolled cigarettes. Patients smoking hand-rolled cigarettes had a smoking history of fewer daily cigarettes and less pack-years tobacco consumed than fabricated cigarette smokers. In this study, hand-rolled cigarettes are more frequently used than shown in national statistics. Smokers of hand-rolled cigarettes may have a greatly increased risk for lung cancer compared with smokers of fabricated cigarettes. PMID- 20298399 TI - Effect of asthma compliance enhancement training on asthma control in patients on combination therapy with salmeterol/fluticasone propionate: a randomised controlled trial. AB - OBJECTIVE: We investigated if a higher proportion of adults with previously uncontrolled asthma can achieve total control when given salmeterol/fluticasone propionate (50/250 microg) bid and compliance enhancement training (CET) compared to those given medication alone. METHODS: Open comparison of stable, but uncontrolled, adult asthmatics. After a 12-week treatment period on salmeterol/fluticasone propionate (period 1), patients who failed to achieve control were randomised to continuing treatment with or without CET for 12 weeks (period 2). The primary end point was the proportion achieving total control of their asthma in 7 of the last 8 consecutive weeks of period 2. RESULTS: A total of 361 subjects (50.4% males, mean age 40.0 +/- 14.4 years) in 29 centres were included, of whom 75.9% were randomised into treatment period 2 (n = 140 in the intervention group). The proportion of subjects achieving total asthma control was 8.8% and 7.6%, respectively, in the intervention and control group [not significant (NS)]. Mean morning peak flow, forced expiratory volume in one second (FEV(1)), asthma symptom score and quality of life improved significantly over the study period in both treatment groups. Furthermore, proportion of days with use of rescue medication declined from 59.7% +/- 34.6% (55.7% +/- 35.3%) during screening to 20.3% +/- 29.2% (19.4% +/- 30.9%) during treatment period 2 (NS). CONCLUSION: CET failed to increase the likelihood of achieving total control in asthmatics on salmeterol/fluticasone propionate compared to subjects receiving medication only. However, both groups had a significant improvement in asthma control. (Clinical Trials.gov number, NCT00351143) PMID- 20298400 TI - Cost-effectiveness of budesonide/formoterol for maintenance and reliever asthma therapy in Denmark--cost-effectiveness analysis based on five randomised controlled trials. AB - BACKGROUND AND AIMS: Budesonide/formoterol maintenance and reliever therapy (Symbicort SMART) is an effective asthma-management regime where patients use budesonide/formoterol both as maintenance treatment and as additional doses as needed to improve overall asthma control by reducing symptoms and exacerbations. The aim of this study was to determine the cost-effectiveness of the Symbicort SMART regime in Denmark vs higher dose inhaled corticosteroid (ICS) plus reliever medication, similar dose inhaled corticosteroid/long-acting beta(2)-agonist (ICS/LABA) combination therapy plus reliever medication or higher dose of inhaled ICS/LABA combination therapy plus reliever medication. METHODS: The cost effectiveness analyses were based on effectiveness and resource utilisation data, which were prospectively collected during the treatment period in five randomised clinical trials (duration: 24 weeks, 26 weeks or 1 year). Economic analyses were conducted from both a health care sector (direct costs) and a societal perspective [total costs, i.e direct costs + indirect costs (sick leave)]. The time horizon for the economic analyses was 1 year. The effectiveness measure used was the number of avoided severe exacerbations per patient per year. RESULTS: Patients treated with budesonide/formoterol maintenance and reliever therapy showed statistically significant fewer severe exacerbations per patient compared with the alternative treatment regimes in all comparisons. Budesonide/formoterol maintenance and reliever therapy was a dominant treatment option when compared with higher dose ICS or higher dose ICS/LABA, i.e. it was more effective at a lower total cost. In two of the three comparisons with a similar ICS/LABA dose, Symbicort SMART was dominant. CONCLUSION: Cost-effectiveness analyses of budesonide/formoterol maintenance and reliever therapy show that the significant reduction in the number of severe exacerbations observed in all the included clinical studies is predominately obtained at lower costs compared with alternative treatment regimes. This indicates that budesonide/formoterol maintenance and reliever therapy is a cost-effective treatment option in a Danish setting. PMID- 20298401 TI - Fatal interstitial lung disease after erlotinib administration in a patient with radiation fibrosis. AB - INTRODUCTION: Although gefitinib used for the treatment of non-small-cell lung cancer is a well-known cause of interstitial lung disease (ILD), few case reports on erlotinib-induced ILD have been issued. The common risk factor of both of these two drug-induced ILDs is idiopathic interstitial pneumonia, but ILD in a patient with radiation fibrosis has not been previously reported. METHODS: Report of a case. RESULTS: We recently experienced a case of fatal erlotinib-induced ILD, diagnosed based on clinical and radiologic findings, which occurred in a patient with radiation fibrosis. A 50-year-old male patient was started on erlotinib as a third-line chemotherapy. Six days after taking erlotinib, a chest radiograph showed rapid progression of reticular infiltration in both lung fields. High-resolution computed tomography scan findings were consistent with ILD, which was sufficient to diagnose as erlotinib-induced ILD. The patient died of respiratory failure after 8 days of steroid infusion and erlotinib discontinuation. CONCLUSION: Our case shows a fatal side effect of erlotinib. This case had radiation fibrosis, so we suggest that radiation fibrosis may be another contributor of the occurrence of ILD in patients taking erlotinib. PMID- 20298403 TI - Disease activity in asthma, more than symptom control and more than eosinophilic inflammation. PMID- 20298404 TI - Current and future use of the mannitol bronchial challenge in everyday clinical practice. AB - OBJECTIVES: Asthma is a disease associated with inflammation, airway hyperresponsiveness (AHR) and airflow limitation. Clinical diagnosis and management of asthma often relies on assessment of lung function and symptom control, but these factors do not always correlate well with underlying inflammation. Bronchial challenge tests (BCTs) assess AHR, and can be used to assist in the diagnosis and management of asthma. DATA SOURCE: Data presented at the symposium 'Use of inhaled mannitol for assessing airways disease' organised by the Allied Respiratory Professionals Assembly (9) of the European Respiratory Society (ERS) at the ERS Congress, Berlin 2008. RESULTS: Indirect challenge tests such as exercise testing, hypertonic saline or adenosine 5'-monophosphate (AMP) are more specific though less sensitive than direct challenge tests (such as methacholine) for identifying patients with active asthma. Indirect BCTs may be used to diagnose exercise-induced bronchoconstriction or AHR consistent with active asthma, to evaluate AHR that will respond to treatment with anti inflammatory drugs and to determine the effectiveness and optimal dosing of such therapy. An ideal indirect challenge test should be standardised and reproducible, and the test result should correlate with the degree of airway inflammation. The mannitol BCT provides a standardised and rapid point-of-need test to identify currently active asthma, and is clinically useful in the identification of patients with asthma who are likely to benefit from inhaled corticosteroid therapy. CONCLUSION: In the future, mannitol BCT may be added to lung function and symptom assessment to aid in the everyday management of asthma. PMID- 20298405 TI - Inflammatory phenotypes in adult asthma: clinical applications. AB - BACKGROUND: The pattern of granulocyte infiltration can be used to identify different inflammatory phenotypes in asthma. Recognized granulocyte phenotypes using induced sputum are eosinophilic (EA), neutrophilic, mixed granulocytic and paucigranulocytic asthma. METHODS: The recognition and importance of inflammatory phenotype analysis using induced sputum in adult asthma are reviewed using published literature. RESULTS: Knowledge of inflammatory phenotype is useful because it relates to treatment response, mechanistic pathways involved in disease pathogenesis and future disease risk. The population attributable risk of asthma because of eosinophilic inflammation is about 50%, and conversely, this means that up to 50% of asthma cannot be attributed to eosinophilic inflammation, and represents asthma associated with non-eosinophilic processes. In these patients, bronchial biopsy shows significantly fewer eosinophils in the bronchial mucosa than subjects with EA. This confirms that non-eosinophilic asthma is a consistent pattern/phenotype in the airway lumen and the airway mucosa. A key aspect of asthma inflammatory phenotype analysis is that it can be applied to individual patients. The underlying principle relates to the association between a clinical response to corticosteroids and the presence of a selective sputum eosinophilia. CONCLUSIONS: Clinically useful applications of induced sputum analysis are the detection of non-adherence to corticosteroid therapy, assessment of adequacy of inhaled corticosteroid therapy, long-term therapy management in asthma, oral corticosteroid dose adjustment in refractory asthma and assessment of occupational asthma. PMID- 20298406 TI - Sarcoidosis-associated pulmonary hypertension: acute vasoresponsiveness to inhaled nitric oxide and the relation to long-term effect of sildenafil. AB - BACKGROUND: Severe pulmonary sarcoidosis is often complicated by pulmonary hypertension (PH) caused by different pathophysiological mechanisms. OBJECTIVES: To assess the acute vasoresponsiveness in patients with sarcoidosis and PH and the relation to the therapeutic effect of sildenafil. METHODS: A retrospective chart review of 25 patients with recalcitrant pulmonary sarcoidosis being evaluated for lung transplantation at our centre. Haemodynamics were evaluated by right heart catheterisation in 24 patients of whom 19 had PH. Eight of the 19 patients received vasodilator challenge with inhaled nitric oxide (iNO). RESULTS: The study group of eight patients (seven men) had a median age of 51 years (range 38 years-58 years). During iNO we observed a reduction in all patients' mean pulmonary arterial pressure (MPAP) of median 9 mmHg (range 1 mmHg-20 mmHg) (P = 0.01) and in all patients' pulmonary vascular resistance of median 2.0 Wood Units (0.7 Wood Units-5.8 Wood Units) (P = 0.01). Acute vasoresponsiveness defined as reduction in MPAP of >or=10 mmHg to a MPAP of 30. Falling asleep in front of the television was the only symptom related to (AHI). Nocturnal dyspnea, daytime sleepiness, generic quality of life or disease-specific quality of life were not related to AHI. CONCLUSIONS: Cheyne-Stokes respiration was not associated with health-related quality of life, daytime sleepiness or nocturnal dyspnea among patients stabilized following treatment for congestive heart failure. PMID- 20298416 TI - Experimental and seasonal exposure to birch pollen in allergic rhinitis and allergic asthma with regard to the inflammatory response. AB - BACKGROUND AND AIMS: Seasonal allergy is an interesting model to study the pathophysiological mechanisms involved in allergic inflammation. However, experimental allergen exposure is easier to perform and standardise. The primary aim of this study was to compare the inflammatory responses to high-dose bronchial challenge and natural exposure during birch pollen season. The second aim was to compare the responses of patients with allergic rhinitis and allergic asthma, respectively to both types of allergen exposure. METHODS: Fifteen birch pollen-allergic patients (seven with asthma and eight with rhinitis) and five healthy individuals were studied during pollen season and after challenge with birch allergen. Symptoms, medication and peak expiratory flow rate (PEFR) were recorded, and blood samples, spirometry and induced sputum were analysed during season and after challenge. RESULTS: Patients with allergic asthma demonstrated a greater bronchial responsiveness to bronchial provocation with birch allergen than patients with rhinitis (P = 0.04) whereas no difference was found regarding nasal challenge. No significant association was found between the level of responsiveness and the inflammatory response after seasonal exposure. Seasonal exposure was related to a more marked systemic inflammatory blood-eosinophil increase than bronchial challenge [(median) (0.25 vs 0.11 x 109/L, P = 0.03)] and after nasal challenge, respectively [(median) (0.25 vs 0.04 x 109/L, P = 0.003)]. A significant correlation in eosinophil cationic protein in induced sputum was found between the experimental and seasonal exposure (rho = 0.62, P = 0.02). CONCLUSIONS: Bronchial allergen challenge with inhalation of birch pollen gives a similar inflammatory response in the airway but less systemic inflammation than seasonal exposure in birch pollen allergic patients with asthma and rhinitis. PMID- 20298417 TI - Neurotrophins in chronic cough: association with asthma but not with cough severity. AB - BACKGROUND AND AIMS: Chronic cough is associated with an enhanced excitability of airway cough receptors, possibly due to action of neurotrophins. The present study aimed to compare the neurotrophin levels between healthy subjects and patients with chronic cough and to analyze the factors associated with these levels. METHODS: Serum and sputum levels of nerve growth factor (NGF), serum levels of brain-derived neurotrophic factor (BDNF), and neurotrophin-3 (NT-3) were analyzed by enzyme immunoassay in 19 healthy subjects and 47 patients with chronic cough. In addition, cough sensitivity to hypertonic saline was assessed, cough diary was kept, Leicester Cough Questionnaire was filled in, peak flow was monitored and spirometry, skin prick tests, exhaled nitric oxide measurement and histamine challenge were performed. RESULTS: The NGF levels did not differ between the healthy subjects and the patients with chronic cough and were not associated with any index describing cough severity. However, these levels in both serum (P = 0.01) and sputum (P = 0.025) samples were associated with asthma. There was a statistically significant association between serum and sputum NGF levels (R = 0.45, P = 0.026). The serum BDNF levels did not differ between the groups and were not associated with any of the background characteristics. The serum NT-3 levels were below the detection limit in most subjects and therefore these data were not analyzed. CONCLUSIONS: Neither chronic cough nor its severity is associated with abnormal neurotrophin levels. High NGF levels among some patients with chronic cough may indicate a presence of asthma. PMID- 20298418 TI - Effect of fluticasone on markers of inflammation and quality of life in steroid naive patients with mild asthma. AB - BACKGROUND AND AIMS: Patients with mild asthma may adapt to symptoms that may be neglected at a medical consultation. Despite active airway inflammation, indicating need for treatment symptoms may be poorly perceived and influence on quality of life. The aim was to find out if markers of asthma activity and quality of life are influenced by inhaled steroids in patients who regard themselves as free of symptoms. METHODS: Seventy steroid-free patients with mild asthma were treated with inhaled fluticasone (250 microg twice daily) or placebo for 3 months in a randomised, double-blind, study. Spirometry with reversibility test, exhaled nitric oxide (NO), bronchial responsiveness to methacholine and eucapnic dry air hyperventilation and quality of life [(Asthma Quality of Life Questionnaire (AQLQ)] were assessed before and after treatment. RESULTS: Fluticasone, but not placebo, decreased methacholine responsiveness. Bronchial responsiveness to dry air and exhaled NO levels was significantly lowered by fluticasone compared with placebo. Quality-of-life scores were high already before treatment and were not significantly altered by treatment. CONCLUSION: Treatment with an inhaled steroid in mild asthmatics altered bronchial responsiveness and exhaled NO levels but did not improve quality of life. In mild asthma, there is thus a space for improvement with regard to inflammatory parameters in patients who have only minor symptoms that are not influenced by treatment. In a long-term perspective, the indication for treatment of surrogate markers remains, however, unclear. PMID- 20298419 TI - Bronchial carcinoid: common manifestation of a rare disorder. PMID- 20298420 TI - Panton-Valentine leukocidin pneumonia: an emerging threat. PMID- 20298421 TI - EFNS guidelines on the molecular diagnosis of channelopathies, epilepsies, migraine, stroke, and dementias. AB - OBJECTIVES: These EFNS guidelines on the molecular diagnosis of channelopathies, including epilepsy and migraine, as well as stroke, and dementia are designed to summarize the possibilities and limitations of molecular genetic techniques and to provide diagnostic criteria for deciding when a molecular diagnostic work-up is indicated. SEARCH STRATEGY: To collect data about planning, conditions, and performance of molecular diagnosis of these disorders, a literature search in various electronic databases was carried out and original papers, meta-analyses, review papers, and guideline recommendations were reviewed. RESULTS: The best level of evidence for genetic testing recommendation (B) can be found for a small number of syndromes, cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, severe myoclonic epilepsy of infancy, familial recurrent hemorrhages, familial Alzheimer's disease, and frontotemporal lobar degeneration. Good practice points can be formulated for a number of other disorders. CONCLUSION: These guidelines are provisional, and the future availability of molecular genetic epidemiological data about the neurogenetic disorders under discussion in our article will allow improved recommendation with an increased level of evidence. PMID- 20298422 TI - Corticolimbic gray matter loss in Parkinson's disease without dementia. AB - BACKGROUND: The relationship between corticolimbic involvement and cognitive dysfunction in non-demented Parkinson's disease (PD) patients has not yet been elucidated. OBJECTIVES: To delineate involvement of the cerebral cortex and limbic structures in non-demented PD and to clarify distributional differences of gray matter loss between non-demented PD with impaired cognition (PD-CI) and without cognitive impairment (PD-NC). METHODS: Operational criteria based on the Clinical Dementia Rating were used to identify PD-CI. Of 40 consecutive non demented patients with PD, 13 were classified as PD-CI and 27 as PD-NC. Comparisons of regional gray matter volume (rGMV) were made amongst the PD-CI, PD NC, and control groups using voxel-based morphometry. RESULTS: Gray matter loss was found extensively in the frontal, temporal, parietal, and occipital cortices in the present non-demented patients with PD. rGMV in the medial frontal and medial occipital cortices was reduced comparably in the PD-NC and PD-CI groups. The severity of gray matter loss in the perisylvian cortices increased in order from the control, to the PD-NC, to the PD-CI groups. rGMV reduction in the lateral and orbital frontal, medial and lateral temporal, medial and lateral parietal, and lateral occipital cortices and cerebellum was found specifically in PD-CI. CONCLUSIONS: Our results suggest that corticolimbic degeneration occurs in non-demented patients with PD, and extensive involvement of the limbic and posterior cortical regions as well as the frontal cortices is associated with cognitive impairment in PD. PMID- 20298423 TI - Brugada syndrome revealed by vertigo caused by cerebellar infarction. PMID- 20298424 TI - The incidence of major stroke subtypes in southern Italy: a population-based study. AB - BACKGROUND AND PURPOSE: Stroke is characterized by well-defined clinical major subtypes, but there are few studies on incidence rates, aetiologies and outcomes in population-based setting. We assessed the age/sex incidence of the major stroke subtypes in a region of Southern Italy. METHODS: We established a multisource, prospective population-based register in Puglia, Southern Italy to identify all residents with a first-ever stroke between 1 January 2001 and 31 December 2002. RESULTS: One hundred and twenty-seven first-ever strokes were diagnosed, and stroke subtype was defined in 119 cases. The incidence rates per 100 000 adjusted to the European population (AEP) were 112 for cerebral infarction (CI), 30 for intracerebral haemorrhage (IH), four for subarachnoid haemorrhage (SH) and nine for undetermined stroke (US). The incidence rates for CI, IH and US approximately doubled with each decade of life and were higher in men. AEP incidence rates for CI in the age groups 45-84 were lower compared to other studies, whilst the corresponding rates for IH were higher. CONCLUSIONS: This population had a lower incidence of CI compared to other population-based studies from Northern Europe and the United States. Furthermore, with the projected increase in the segment of the very old in the general population, our data indicate that both CI and IH will dramatically increase in the near future. PMID- 20298425 TI - Fish consumption and dementia: keep the vitamin D in memory. PMID- 20298426 TI - Serum inflammatory proteins and frontal lobe dysfunction in patients with cardiovascular risk factors. AB - BACKGROUND: Recent studies have shown that the levels of circulating inflammatory markers are associated with cognitive decline and cerebral small-vessel disease. Frontal lobe dysfunction is believed to be a relatively characteristic neuropsychological symptom in vascular cognitive impairment caused by cerebral small-vessel disease. The purpose of this study was to investigate whether the levels of serum inflammatory markers are associated with frontal lobe dysfunction, particularly executive dysfunction. METHODS: Between January 2003 and September 2007, 388 patients who had one or more atherosclerotic risk factors and subsequently underwent brain MRI and neuropsychological testing including mini-mental state examination (MMSE), frontal assessment battery (FAB), and modified Stroop test were enrolled in this study. We evaluated the effect of serum levels of inflammatory markers and white matter lesions on frontal lobe function. RESULTS: The FAB score was negatively correlated with serum inflammatory marker levels (hsCRP; r = -0.170, IL-6; r = -0.143, IL-18; r = 0.175) and white matter lesions. In the modified Stroop test, interference measure was positively correlated with the levels of hsCRP (r = -0.198), and IL 18 (r = -0.152), and white matter lesions. However, the MMSE score was not correlated with either inflammatory marker levels. The association between hsCRP and FAB score or interference measure remained significant when controlling for other confounding factors and MRI findings. CONCLUSIONS: The circulating level of hsCRP is associated with frontal lobe dysfunction in patients with cardiovascular risk factors independent of white matter lesions in brain MRI. PMID- 20298427 TI - Dysautonomia after severe traumatic brain injury. AB - BACKGROUND: Dysautonomia after traumatic brain injury (TBI) is characterized by episodes of increased heart rate, respiratory rate, temperature, blood pressure, muscle tone, decorticate or decerebrate posturing, and profuse sweating. This study addresses the incidence of dysautonomia after severe TBI, the clinical variables that are associated with dysautonomia, and the functional outcome of patients with dysautonomia. METHODS: A historic cohort study in patients with severe TBI [Glasgow Coma Scale (GCS) < or = 8 on admission]. RESULTS: Seventy-six of 119 patients survived and were eligible for follow-up. The incidence of dysautonomia was 11.8%. Episodes of dysautonomia were prevalent during a mean period of 20.1 days (range 3-68) and were often initiated by discomfort. Patients with dysautonomia showed significant longer periods of coma (24.78 vs. 7.99 days) and mechanical ventilation (22.67 vs. 7.21 days). Dysautonomia was associated with diffuse axonal injury (DAI) [relative risk (RR) 20.83, CI 4.92-83.33] and the development of spasticity (RR 16.94, CI 3.96-71.42). Patients with dysautonomia experienced more secondary complications. They tended to have poorer outcome. CONCLUSIONS: Dysautonomia occurs in approximately 10% of patients surviving severe TBI and is associated with DAI and the development of spasticity at follow-up. The initiation of dysautonomia by discomfort supports the Excitatory: Inhibitory Ratio model as pathophysiological mechanism. PMID- 20298428 TI - EFNS guidelines on neuropathic pain assessment: revised 2009. AB - BACKGROUND AND PURPOSE: We have revised the previous EFNS guidelines on neuropathic pain (NP) assessment, which aimed to provide recommendations for the diagnostic process, screening tools and questionnaires, quantitative sensory testing (QST), microneurography, pain-related reflexes and evoked potentials, functional neuroimaging and skin biopsy. METHODS: We have checked and rated the literature published in the period 2004-2009, according to the EFNS method of classification for diagnostic procedures. RESULTS: Most of the previous recommendations were reinforced by the new studies. The main revisions relate to: (i) the new definition of NP and a diagnostic grading system; (ii) several new validated clinical screening tools that identify NP components, and questionnaires which assess the different types of NP; (iii) recent high-quality studies on laser-evoked potentials (LEPs) and skin biopsy. CONCLUSIONS: History and bedside examination are still fundamental to a correct diagnosis, whilst screening tools and questionnaires are useful in indicating probable NP; QST is also useful for indicating the latter, and to assess provoked pains and treatment response. Amongst laboratory tests, LEPs are the best tool for assessing Adelta pathway dysfunction, and skin biopsy for assessing neuropathies with distal loss of unmyelinated nerve fibres. PMID- 20298429 TI - The contribution of gene movement to the "two rules of speciation". AB - The two "rules of speciation"--the Large X-effect and Haldane's rule--hold throughout the animal kingdom, but the underlying genetic mechanisms that cause them are still unclear. Two predominant explanations--the "dominance theory" and faster male evolution--both have some empirical support, suggesting that the genetic basis of these rules is likely multifarious. We revisit one historical explanation for these rules, based on dysfunctional genetic interactions involving genes recently moved between chromosomes. We suggest that gene movement specifically off or onto the X chromosome is another mechanism that could contribute to the two rules, especially as X chromosome movements can be subject to unique sex-specific and sex chromosome specific consequences in hybrids. Our hypothesis is supported by patterns emerging from comparative genomic data, including a strong bias in interchromosomal gene movements involving the X and an overrepresentation of male reproductive functions among chromosomally relocated genes. In addition, our model indicates that the contribution of gene movement to the two rules in any specific group will depend upon key developmental and reproductive parameters that are taxon specific. We provide several testable predictions that can be used to assess the importance of gene movement as a contributor to these rules in the future. PMID- 20298430 TI - Promiscuity and the rate of molecular evolution at primate immunity genes. AB - Recently, a positive correlation between basal leukocyte counts and mating system across primates suggested that sexual promiscuity could be an important determinant of the evolution of the immune system. Motivated by this idea, we examined the patterns of molecular evolution of 15 immune defense genes in primates in relation to promiscuity and other variables expected to affect disease risk. We obtained maximum likelihood estimates of the rate of protein evolution for terminal branches of the primate phylogeny at these genes. Using phylogenetically independent contrasts, we found that immunity genes evolve faster in more promiscuous species, but only for a subset of genes that interact closely with pathogens. We also observed a significantly greater proportion of branches under positive selection in the more promiscuous species. Analyses of independent contrasts also showed a positive effect of group size. However, this effect was not restricted to genes that interact closely with pathogens, and no differences were observed in the proportion of branches under positive selection in species with small and large groups. Together, these results suggest that mating system has influenced the evolution of some immunity genes in primates, possibly due to increased risk of acquiring sexually transmitted diseases in species with higher levels of promiscuity. PMID- 20298431 TI - Gene flow and species delimitation: a case study of two pine species with overlapping distributions in southeast China. AB - Species delimitation detected by molecular markers is complicated by introgression and incomplete lineage sorting between species. Recent modeling suggests that fixed genetic differences between species are highly related to rates of intraspecific gene flow. However, it remains unclear whether such differences are due to high levels of intraspecific gene flow overriding the spread of introgressed alleles or favoring rapid lineage sorting between species. In pines, chloroplast (cp) and mitochondrial (mt) DNAs are normally paternally and maternally inherited, respectively, and thus their relative rates of intraspecific gene flow are expected to be high and low, respectively. In this study, we used two pine species with overlapping geographical distributions in southeast China, P. massoniana and P. hwangshanensis, as a model system to examine the association between organelle gene flow and variation within and between species. We found that cpDNA variation across these two pine species is more species specific than mtDNA variation and almost delimits taxonomic boundaries. The shared mt/cp DNA genetic variation between species shows no bias in regard to parapatric versus allopatric species' distributions. Our results therefore support the hypothesis that high intraspecific gene flow has accelerated cpDNA lineage sorting between these two pine species. PMID- 20298432 TI - When gaps really are gaps: statistical phylogeography of hydrothermal vent invertebrates. AB - The invertebrate animals endemic to deep-sea hydrothermal vents are distributed intermittently along relatively linear oceanic ridge axes. A one-dimensional stepping-stone model, therefore, provides a reasonable starting hypothesis of population structure for these species. Nevertheless, population genetic studies of many species from eastern Pacific vents did not detect the expected signatures of isolation-by-distance (IBD). Instead, distinct patterns of geographical subdivision have been attributed to the unique dispersal modes of individual species, topographical discontinuities of the ridge axes, nonequilibrium metapopulation scenarios and cryptic species. Here, we reexamined these inferences in light of expectations generated by computer simulations of a one dimensional stepping-stone model. We evaluated whether the previously inferred subdivisions are statistically robust to an alternative explanation that continuous stepping-stone migration has occurred along the ridge axes but discontinuities in the sampling design (gaps) have generated the apparent disjunctions. We found that previous inferences about barriers to gene flow (vicariance) were supported in many cases, but that failures to detect evidence for IBD could be explained by low statistical power associated with the sampling effort. The simulation approaches presented here might be useful for testing the significance of inferred phylogeographic gaps in other species. PMID- 20298433 TI - Interaction of endothelial cell-selective adhesion molecule and MAGI-1 promotes mature cell-cell adhesion via activation of RhoA. AB - Endothelial cell-selective adhesion molecule (ESAM) is a member of the immunoglobulin superfamily and mediates homophilic adhesion between endothelial cells. ESAM has been shown to bind to membrane-associated guanylate kinase (MAGUK) with inverted domain structure 1 (MAGI-1), but the interaction between these molecules remains unknown. We investigated the role of ESAM in the subcellular localization of MAGI-1 and cell adhesion by means of transfection experiments using Chinese hamster ovary (CHO) cells. Overexpression of ESAM recruited MAGI-1 to the cell-cell contact area. The intracellular domain of ESAM was necessary for the recruitment of MAGI-1 to the cell contact area, but did not participate in the initial cell-cell adhesion. Cell dissociation assays revealed that colocalization of ESAM and MAGI-1 promoted actin polymerization through the postsynaptic density 95/discs large/zonula occludens-1 (PDZ) domain and resulted in firm cell-cell adhesion, which was inhibited by an actin polymerization inhibitor. When the cells attach to each other, colocalization of ESAM and MAGI-1 can lead to the actin polymerization at intracellular contacts. Interaction of ESAM with MAGI-1 activated RhoA, and ESAM-mediated MAGI-1 recruitment to the cell membrane and mature cell adhesion were inhibited by a RhoA inhibitor. These findings suggest that ESAM may regulate MAGI-1 recruitment to the cell contacts, and subsequently promote actin polymerization and mature cell-cell adhesion through a RhoA-dependent mechanism. PMID- 20298434 TI - Regulation of asymmetric positioning of nuclei by Wnt and Src signaling and its roles in POP-1/TCF nuclear asymmetry in Caenorhabditis elegans. AB - In various polarized cells, positions of nuclei are often off-center. However, extrinsic signals regulating nuclear off-centering and its biologic roles remain to be elucidated. In Caenorhabditis elegans, polarity of the EMS cell undergoing asymmetric division is regulated by the MOM-2/Wnt and MES-1 signals from its posterior neighbor P2 cell. We show that after divisions of different cells including EMS, the nuclei of the posterior but not anterior daughter cells are anchored to the posterior cell cortex via centrosomes. We also show that this nuclear anchoring is regulated by components of the Wnt pathway and SRC-1 that functions in MES-1 signaling. To understand the biologic roles of nuclear anchoring, we analyzed its effects on asymmetric nuclear localization of POP 1/TCF that is also regulated by Wnt and Src signaling. We found that in mom-2 mutants where the nuclear anchoring and POP-1 asymmetry is partially inhibited, the proximity of the nucleus to the cell cortex correlated with POP-1 asymmetry. Furthermore, in mutants of mom-2, the defect in the anchoring is clearly correlated with that of asymmetric fate determination. These results suggest that the asymmetric nuclear anchoring functions in asymmetric division by enhancing POP-1 asymmetry. PMID- 20298435 TI - Contribution of dynein light intermediate and intermediate chains to subcellular localization of the dynein-dynactin motor complex in Schizosaccharomyces pombe. AB - In fission yeast Schizosaccharomyces pombe, cytoplasmic dynein drives oscillatory nuclear movement during meiotic prophase, which may facilitate pairing of homologous chromosomes. Here, we report the identification of a dynein light intermediate chain (LIC) in fission yeast, termed Dli1p, and show that Dli1p and dynein intermediate chain (IC) Dic1p are essential for the appropriate subcellular localization and proper function of dynein during meiotic prophase. Expression of both the dli1 and dic1 genes was observed only in cells undergoing meiosis. Dli1p interacted and colocalized with dynein heavy chain Dhc1p. The subcellular localization of Dli1p was dependent on Dhc1p, and vice versa. The Dhc1p-Dli1p subcomplex could localize to the spindle pole body (SPB) with no aid of Dic1p and dynactin subunit Ssm4p, but its localization to microtubules was dependent on these two proteins. Dic1p localized to microtubules depending on Ssm4p, but not on Dhc1p and Dli1p. Its localization to the SPB, however, was dependent on Dhc1p and Dli1p. Localization of Ssm4p to the SPB was largely dependent on Dhc1p, Dli1p and Dic1p. Thus, Dli1p and Dic1p contribute differently in localizing the dynein-dynactin motor complex to organelles, providing novel insight into the in vivo function of dynein subunits in fission yeast. PMID- 20298436 TI - Role of N-end rule ubiquitin ligases UBR1 and UBR2 in regulating the leucine-mTOR signaling pathway. AB - Of 20 natural amino acids, leucine is particularly important for promoting cellular protein synthesis. The effect of leucine involves mammalian target of rapamycin (mTOR), a key protein kinase controlling cell growth. Leucine enhances mTOR-mediated phosphorylation of S6K1 and 4E-BP, thereby promoting protein synthesis. However, how the presence of leucine is sensed and transmitted to mTOR is poorly understood. Here, we show evidence that UBR1 and UBR2 might be cellular targets of leucine. UBR1 and UBR2 are E3 ubiquitin ligases that recognize the identity of N-terminal residues and contribute to selective destabilization of target proteins according to the N-end rule. Using leucine-immobilized affinity beads, we identified UBR1 and UBR2 as leucine-binding proteins from leucine responsive rat hepatoma H4IIE cells. Over-expression of UBR1 or UBR2 resulted in a reduction in mTOR-dependent S6K1 phosphorylation, whereas knockdown of UBR1 or UBR2 increased S6K1 phosphorylation in amino acid-starved human 293T cells. We also found that leucine binds to the substrate-recognition domain of UBR2 and inhibits degradation of N-end rule substrates in vitro. These findings suggest that UBR1 and UBR2 are negative regulators of the leucine-mTOR signaling pathway. Leucine might activate this pathway in part through inhibition of their ubiquitin ligase activity. PMID- 20298437 TI - DPPA4 modulates chromatin structure via association with DNA and core histone H3 in mouse embryonic stem cells. AB - Developmental pluripotency associated 4 (DPPA4) is one of the uncharacterized genes that is highly expressed in embryonic stem (ES) cells. DPPA4 is associated with active chromatin and involved in the pluripotency of mouse ES cells. However, the biological function of DPPA4 remains poorly understood. In this study, we performed fluorescence recovery after photobleaching (FRAP) analysis to examine the dynamics of DPPA4 in ES cells. FRAP analysis showed that the mobility of DPPA4 is similar to that of histone H1. In addition, biochemical analysis with purified proteins and immunoprecipitation analysis showed that DPPA4 directly binds to both DNA and core histone H3. The analysis using truncated proteins indicated that DPPA4 is associated with DNA via the N-terminal region and histone H3 via the C-terminal region. In vitro assembled chromatin showed resistance to micrococcal nuclease (MNase) digestion in the presence of DPPA4. Moreover, MNase assay and FRAP analysis with the truncated proteins implies that DPPA4 binding to both DNA and histone H3 is necessary for the chromatin structure resistant to MNase and for the proper localization of DPPA4 in ES cell nuclei. These results suggest that DPPA4 modulates the chromatin structure in association with DNA and histone H3 in ES cells. PMID- 20298438 TI - Distinct functionalities of bone morphogenetic protein antagonists during fracture healing in mice. AB - The bone morphogenetic protein (BMP) family of growth factors plays critical roles in bone formation. BMPs are regulated at multiple levels by various BMP antagonists. This study investigated how BMP antagonists are integrated into the cascade of events of bone formation during fracture healing. Forty mice underwent a controlled femur fracture; tissue samples at the fracture site were harvested at days 1, 3, 7, 14 and 21 after fracture, for quantification of the expression of BMPs and BMP antagonists. During fracture healing, BMP-2, -4 and -7 were up regulated, but BMPR-1A and BMPR-2 showed reduced expression after day 14. Among BMP antagonists, the expressions of PRDC, SOST, Smad7, GREM1 and CERBERUS were generally down-regulated during fracture healing. In contrast, Noggin was significantly up-regulated in the first week after fracture; 7 days after fracture, other BMP antagonists, including DAN, CHRD, Smad6 and BAMBI, also showed significantly increased expression. In conclusion, this study indicates that BMP antagonists can be divided into two functional groups in relation to fracture healing: (1) those whose suppression may be essential for the initiation of osteogenesis; (2) those that are upregulated and may function in the remodeling of newly formed bone. PMID- 20298439 TI - Function of the shoulder muscles during arm elevation: an assessment using positron emission tomography. AB - Although 2-deoxy-2-[(18)F]fluoro-D-glucose (FDG) positron emission tomography (PET) has been used for the assessment of skeletal muscle activities, its application to the shoulder muscles is only sparse. The purpose of this study was to investigate the activities of the shoulder muscles during arm elevation using PET. Six healthy volunteers performed an arm elevation exercise before and after FDG injection. The exercise consisted of 200 repetitions of arm elevation in the scapular plane with a 0.25-kg weight fixed to the wrist on both arms. PET examination was performed 50 min after FDG injection. For control data, PET scan was repeated for each subject on a separate day without any exercise. The volume of interest was established for each shoulder muscle. The subscapularis was divided into three portions (superior, middle, and inferior). The standardized uptake value (SUV) was calculated in each muscle to quantify its activity. The SUVs increased significantly after exercise in the deltoid, supraspinatus, and the superior portion of subscapularis. Among three divided portions of the subscapularis, the SUV of the superior one-third was significantly greater than the rest of the muscle after exercise. Our current study clearly indicated that there were two functionally different portions in the subscapularis muscle and the superior one-third played an important role during arm elevation in the scapular plane. PMID- 20298440 TI - Heritability of anti-predatory traits: vigilance and locomotor performance in marmots. AB - Animals must allocate some proportion of their time to detecting predators. In birds and mammals, such anti-predator vigilance has been well studied, and we know that it may be influenced by a variety of intrinsic and extrinsic factors. Despite hundreds of studies focusing on vigilance and suggestions that there are individual differences in vigilance, there have been no prior studies examining its heritability in the field. Here, we present one of the first reports of (additive) genetic variation in vigilance. Using a restricted maximum likelihood procedure, we found that, in yellow-bellied marmots (Marmota flaviventris), the heritability of locomotor ability (h(2)=0.21), and especially vigilance (h(2) = 0.08), is low. These modest heritability estimates suggest great environmental variation or a history of directional selection eliminating genetic variation in these traits. We also found a significant phenotypic (r(P) = -0.09 +/- 0.04, P = 0.024) and a substantial, but not significant, genetic correlation (r(A) = -0.57 +/- 0.28, P = 0.082) between the two traits (slower animals are less vigilant while foraging). We found no evidence of differential survival or longevity associated with particular phenotypes of either trait. The genetic correlation may persist because of environmental heterogeneity and genotype-by-environment interactions maintaining the correlation, or because there are two ways to solve the problem of foraging in exposed areas: be very vigilant and rely on early detection coupled with speed to escape, or reduce vigilance to minimize time spent in an exposed location. Both strategies seem to be equally successful, and this 'locomotor ability-wariness' syndrome may therefore allow slow animals to compensate behaviourally for their impaired locomotor ability. PMID- 20298441 TI - Developmental acclimation affects clinal variation in stress resistance traits in Drosophila buzzatii. AB - Patterns of clinal genetic variation in Drosophila are often characterized after rearing at constant temperatures. However, clinal patterns might change after acclimation if populations differ in their plastic response to fluctuating environments. We studied longevity, starvation and heat knock-down resistance after development at either constant or fluctuating temperatures in nine Drosophila buzzatii populations collected along an altitudinal gradient in Tenerife, Spain. Flies that developed at fluctuating temperatures had higher stress resistance despite experiencing a slightly lower average temperature than those at constant temperatures. Genetic variation along the gradient was found in both stress-resistance traits. Because Q(ST) values greatly exceeded F(ST) values, genetic drift could not explain this diversification. In general, differences among populations were larger after rearing at fluctuating temperatures, especially in heat knock-down, for which clinal patterns disappeared when flies were reared at constant temperatures. This result emphasizes the importance of determining whether populations originating from different environments differ in their plastic responses to stress. PMID- 20298442 TI - The outcome of sperm competition is affected by behavioural and anatomical reproductive traits in a simultaneously hermaphroditic land snail. AB - Sperm competition is important in species with reproductive strategies that involve multiple mating and prolonged sperm storage such as the simultaneously hermaphroditic land snail Cornu aspersum. Double mating trials in this species have revealed that mating order and courtship behaviour affect paternity success. We investigated the effect of behavioural and anatomical reproductive traits on paternity success from triple mating trials. Triple mating resulted in triple fertilization in 58% of the cases whereas zero paternity was observed in 16% of sperm donors. Third sperm donors achieved higher paternity followed by first and second sperm donors. Snails with a longer epiphallus, the spermatophore forming organ, sired more offspring regardless of their mating order. Genetic compatibility between sperm donor and recipient did not influence paternity success. The results of the present study identified mating order and epiphallus length, as traits affecting the outcome of sperm competition in this species. PMID- 20298443 TI - Sex chromosome evolution in the clam shrimp, Eulimnadia texana. AB - Chromosomes that determine sex are predicted to evolve differently than autosomes: a lack of recombination on one of the two sex chromosomes is predicted to allow an accumulation of deleterious alleles that eventually leads to reduced functionality and potential physical degradation of the nonrecombining chromosome. Because these changes should occur at an elevated evolutionary rate, it is difficult to find appropriate species in which to test these evolutionary predictions. The unique genetic sex-determining mechanism of the crustacean Eulimnadia texana prevents major chromosome degeneration because of expression of both 'proto-sex' (i.e. early stage of development) chromosomes in homozygous form (ZZ and WW). Herein, we exploit this unique genetic system to examine the predicted accumulation of deleterious alleles by comparing both homogametic sexual types to their heterogametic counterpart. We report differences in crossing over in a sex-linked region in the ZW hermaphrodites (approximately 3%) relative to the ZZ males (approximately 21%), indicative of cross-over suppression in the ZW hermaphrodites. Additionally, we report that both ZZ and WW genotypes have reduced fitness relative to ZW hermaphrodites, which is consistent with the prediction of harboured recessive mutations embedded on both the Z and the W chromosomes. These results suggest that the proto-sex chromosomes in E. texana accumulate recessive deleterious alleles. We hypothesize that recessive deleterious alleles of large effect cannot accumulate because of expression in both ZZ and WW individuals, keeping both chromosomes from losing significant function. PMID- 20298444 TI - Insularity and the evolution of melanism, sexual dichromatism and body size in the worldwide-distributed barn owl. AB - Island biogeography has provided fundamental hypotheses in population genetics, ecology and evolutionary biology. Insular populations usually face different feeding conditions, predation pressure, intraspecific and interspecific competition than continental populations. This so-called island syndrome can promote the evolution of specific phenotypes like a small (or large) body size and a light (or dark) colouration as well as influence the evolution of sexual dimorphism. To examine whether insularity leads to phenotypic differentiation in a consistent way in a worldwide-distributed nonmigratory species, we compared body size, body shape and colouration between insular and continental barn owl (Tyto alba) populations by controlling indirectly for phylogeny. This species is suitable because it varies in pheomelanin-based colouration from reddish-brown to white, and it displays eumelanic black spots for which the number and size vary between individuals, populations and species. Females are on average darker pheomelanic and display more and larger eumelanic spots than males. Our results show that on islands barn owls exhibited smaller and fewer eumelanic spots and lighter pheomelanic colouration, and shorter wings than on continents. Sexual dimorphism in pheomelanin-based colouration was less pronounced on islands than continents (i.e. on islands males tended to be as pheomelanic as females), and on small islands owls were redder pheomelanic and smaller in size than owls living on larger islands. Sexual dimorphism in the size of eumelanic spots was more pronounced (i.e. females displayed much larger spots than males) in barn owls living on islands located further away from a continent. Our study indicates that insular conditions drive the evolution towards a lower degree of eumelanism, smaller body size and affects the evolution of sexual dichromatism in melanin based colour traits. The effect of insularity was more pronounced on body size and shape than on melanic traits. PMID- 20298445 TI - Changes in skin mucus of common carp, Cyprinus carpio L., after exposure to water with a high bacterial load. AB - Water in aquaculture systems may contain a high load of microorganisms. Reduction in overall bacterial tank water load improves fish health and growth parameters. In this study, the effect of an increase of overall bacterial load in tank water on carp skin mucus was assessed. Intracellular and released high molecular weight glycoproteins (HMGs) of carp skin mucus were analysed for changes using histological, histochemical and biochemical techniques. Increase of bacterial load did not induce obvious clinical responses in carp, but the skin of exposed carp responded quickly. The amount of skin mucus HMGs isolated increased as well as their total glycosylation. An increased goblet cell number was observed for all carbohydrate stainings, but most clearly for acidic glycoconjugates. A change in the terminal presence of some sugars was also seen. After the initial response of carp, an adaptation to the higher bacterial load in the water appeared to occur as mucins had a higher glycosylation. The changes observed suggest that these skin mucus adaptations are part of a primary defence mechanism of mucosal epithelia, even at a low pathogenic pressure. PMID- 20298446 TI - Evaluation of histopathology, real-time PCR and virus isolation for diagnosis of infectious salmon anaemia in Norwegian salmon using latent class analysis. PMID- 20298447 TI - Protection against heterologous Streptococcus iniae isolates using a modified bacterin vaccine in Nile tilapia, Oreochromis niloticus (L.). AB - Streptococcus iniae is a significant pathogen impacting aquaculture production worldwide. The objectives of this study were to determine whether a developed modified S. iniae (ARS-98-60) bacterin vaccine is efficacious in Nile tilapia, Oreochromis niloticus (L.), against challenge with heterologous isolates from diverse geographical locations and to evaluate protein and antigenic variability among the isolates tested. Two groups of tilapia (approximately 5 g) were intraperitoneally (IP) vaccinated with 100 microL of the vaccine or sham vaccinated with 100 microL of sterile tryptic soy broth and held for 28 days. Fish were challenged with each isolate by IP injection of 2-3 x 10(7) CFU per fish using calcein to mark fish prior to cohabitation for challenge. The results demonstrated significant protection against all challenge isolates, and relative percent survivals ranged from 79% to 100%. SDS-PAGE analysis of whole-cell lysate proteins from the S. iniae isolates demonstrated similar protein profiles between 10 and 31 kDa and variation in profiles between 35 and 100 kDa. Western blot analysis using antiserum from vaccinated fish (ARS-98-60) demonstrated shared immunogenic proteins among all isolates in the molecular mass range of 22-35 kDa and high molecular mass material >150 kDa. The results suggest that the developed S. iniae vaccine has broad ranging protection among isolates exhibiting different protein profiles. PMID- 20298448 TI - White spot syndrome virus in wild penaeid shrimp caught in coastal and offshore waters in the southern Atlantic Ocean. PMID- 20298449 TI - The response of intestinal mucous cells to the presence of enteric helminths: their distribution, histochemistry and fine structure. AB - Histochemical and ultrastructural investigations were conducted on the mucous cells of the intestine of brown trout, Salmo trutta L., naturally infected with the cestode Cyathocephalus truncatus (Pallas, 1781) and the acanthocephalan Echinorhynchus truttae Shrank, 1788. A subpopulation of 45 S. trutta were examined of which 15 specimens harboured E. truttae, 15 of which were infected with C. truncatus and 15 fish, the control group, were uninfected. In histological sections, hyperplasia and hypertrophy of the mucous cells were evident at the site of parasite infection. Enhanced mucus secretion was also recorded in infected fish. The number of mucous cells close to the site of parasite attachment within the intestine was significantly higher than the number detected in uninfected individuals and in infected individuals at sites 1 cm or greater from the point of parasite attachment. There were no significant differences between the number of mucous cells found at the latter two sites. Alcian blue and periodic acid-Schiff's staining of representative histological sections revealed a significant increase in the number of mucous cells staining positively for acid glycoconjugates compared to the number of cells found in the intestines of uninfected S. trutta. In transmission electron microscopy sections, each mucous cell typically possessed an elongated, basally positioned nucleus. The cytoplasm was observed to possess numerous electron dense and lucent vesicles, in addition to well-developed rough endoplasmic reticulum, Golgi apparatus and a few round mitochondria. PMID- 20298450 TI - Tetracapsuloides bryosalmonae in spawning pink salmon, Oncorhynchus gorbuscha (Walbaum), in the Quinsam River, British Columbia, Canada. PMID- 20298451 TI - Clinical white spot disease status in Penaeus monodon during the middle of the culture period - its epidemiological significance. PMID- 20298452 TI - Treatment development for systemic Tetrahymena sp. infection in guppies, Poecilia reticulata Peters. AB - Antibacterial and antiparasitic agents and a cysteine protease inhibitor (E-64) were tested against Tetrahymena infection, a serious problem in guppy production worldwide. Chemicals were tested in vitro by a colorimetric assay for Tetrahymena survival. The most effective were niclosamide, albendazole and chloroquine, with 23%, 35% and 60% survival, respectively, following 2-h exposure to 100 ppm. Longer incubation periods resulted in greater reductions in survival. Niclosamide was further studied in vivo at different dosages, administered orally to Tetrahymena-infected guppies. Mortality rates were significantly lower in all treatment groups; in trial I, 30% and 33% mortality in 5 and 40 mg kg(-1) niclosamide-fed fish vs. 59% mortality in controls; in trial II, 35%, 13% and 10% in 50, 100 and 200 mg kg(-1) niclosamide-fed fish vs. 64% in controls. The effect of the cysteine protease inhibitor E64 was tested in tissue culture, by measuring histolytic activity of the parasite (Tet-NI) on a guppy-fin cell line, based on cell depletion. Tet-NI feeding activity was significantly reduced following pretreatment with E-64 relative to non-treated Tet-NI. E-64-pretreated Tet-NI was injected i.p. into guppies: recorded mortality rates were significantly lower (35%) than that in non-treated Tet-NI (60%), suggesting inhibition of the parasite's cysteine protease as a possible therapeutic approach. PMID- 20298453 TI - First description of atypical furunculosis in freshwater farmed Atlantic salmon, Salmo salar L., in Chile. AB - We report the first isolation, identification and characterization of a group of Chilean strains of atypical Aeromonas salmonicida isolated from freshwater farmed Atlantic salmon, Salmo salar. Affected fish showed superficial ulcers and pale liver with or without petechial haemorrhages. Outbreaks of the disease occurred in two farms in the south of Chile about 2200 km apart. Five strains were isolated in pure culture and identified by serological assays and immunofluorescence tests as belonging to Aeromonas salmonicida. Although the bacterial isolates were phenotypically homogeneous, minor differences with the reference strain A. salmonicida subsp. salmonicida ATCC 33658 were noted. Three specific primer sets and partial 16S rRNA gene sequencing allowed the identification of the Chilean isolates as atypical A. salmonicida, with A. salmonicida subsp. achromogenes and A. salmonicida subsp. masoucida as their closest relatives (100% sequence similarity). Molecular typing indicated that the atypical isolates belong to two genetic groups that were associated with the geographical origin. PMID- 20298454 TI - Molecular evolution of the thyrotrophin-releasing hormone precursor in vertebrates: insights from comparative genomics. AB - Human preprothyrotrophin-releasing hormone (ppTRH) includes six copies of the TRH sequence, the rat and mouse precursors have five, and those of non-mammalian vertebrates have up to eight. In the present study, the evolutionary basis of this variation was investigated using ppTRH gene sequences extracted from available vertebrate genomic databases. A structure based on eight TRH repeats appears to be the norm for non-mammalian vertebrates, but in all mammals except monotremes this number is reduced to a maximum of six. In some species, one (or more) of the TRH repeats has been mutated, probably rendering it functionless and, in a few species, one or two copies of the TRH sequence have been deleted completely. Sequences of regions between the TRH sequences are poorly conserved, despite reports that several active peptides are produced from these regions. The 5' untranslated region of ppTRH is also very variable but, in eutherians, the promoter region immediately upstream of the gene is quite strongly conserved. In particular, those sequences identified as being involved in transcriptional regulation are well conserved in most eutherians, although they are largely absent from other vertebrates. In most species, gene order around the ppTRH locus is conserved, although exceptions include man and chimpanzee, as well as rat and mouse. The comparative genomics approach thus provides a wider view than previously available of the range of ppTRH genes in vertebrates, and of the species specificity displayed by this molecule. PMID- 20298455 TI - Hepatic-portal vein infusions of glucagon-like peptide-1 reduce meal size and increase c-Fos expression in the nucleus tractus solitarii, area postrema and central nucleus of the amygdala in rats. AB - We recently reported that brief, remotely controlled intrameal hepatic-portal vein infusions of glucagon-like peptide-1 (GLP-1) reduced spontaneous meal size in rats. To investigate the neurobehavioural correlates of this effect, we equipped male Sprague-Dawley rats with hepatic-portal vein catheters and assessed (i) the effect on eating of remotely triggered infusions of GLP-1 (1 nmol/kg, 5 min) or vehicle during the first nocturnal meal after 3 h of food deprivation and (ii) the effect of identical infusions performed at dark onset on c-Fos expression in several brain areas involved in the control of eating. GLP-1 reduced (P < 0.05) the size of the first nocturnal meal and increased its satiety ratio. Also, GLP-1 increased (P < 0.05) the number of c-Fos-expressing cells in the nucleus tractus solitarii, the area postrema and the central nucleus of the amygdala, but not in the arcuate or paraventricular hypothalamic nuclei. These data suggest that the nucleus tractus solitarii, the area postrema and the central nucleus of the amygdala play a role in the eating-inhibitory actions of GLP-1 infused into the hepatic-portal vein; it remains to be established whether activation of these brain nuclei reflect satiation, aversion, or both. PMID- 20298456 TI - Influence of ghrelin and growth hormone deficiency on AMP-activated protein kinase and hypothalamic lipid metabolism. AB - Current evidence demonstrates that the stomach-derived hormone ghrelin, a potent growth hormone (GH) secretagogue, promotes feeding through a mechanism involving the short-term activation of hypothalamic AMP-activated protein kinase (AMPK), which in turn results in decreased hypothalamic levels of malonyl-CoA and increased carnitine palmitoyltransferase 1 (CPT1) activity. Despite this evidence, no data have been reported about the effect of chronic, central ghrelin administration on hypothalamic fatty acid metabolism. In the present study, we examined the differences in hypothalamic fatty acid metabolism in the presence and absence of GH, by using a model for the study of GH-deficiency, namely the spontaneous dwarf rat and the effect of long-term central ghrelin treatment and starvation on hypothalamic fatty acid metabolism in this animal model. Our data showed that GH-deficiency induces reductions in both de novo lipogenesis and beta oxidation pathways in the hypothalamus. Thus, dwarf rats display reductions in fatty acid synthase (FAS) mRNA expression both in the ventromedial nucleus of the hypothalamus (VMH) and whole hypothalamus, as well as in FAS protein and activity. CPT1 activity was also reduced. In addition, in the present study, we show that chronic ghrelin treatment does not promote AMPK-induced changes in the overall fluxes of hypothalamic fatty acid metabolism in normal rats and that this effect is independent of GH status. By contrast, we demonstrated that both chronic ghrelin and fasting decreased FAS mRNA expression in the VMH of normal rats but not dwarf rats, suggesting GH status dependency. Overall, these results suggest that ghrelin plays a dual time-dependent role in modulating hypothalamic lipid metabolism. Understanding the molecular mechanism underlying the interplay between GH and ghrelin on hypothalamic lipid metabolism will allow new strategies for the design and development of suitable drugs for the treatment of GH deficiency, obesity and its comorbidities. PMID- 20298457 TI - Stress response of prolactin-releasing peptide knockout mice as to glucocorticoid secretion. AB - Prolactin-releasing peptide (PrRP) is known to have functions in prolactin secretion, stress responses, cardiovascular regulation and food intake suppression. In addition, PrRP-knockout (KO) male mice show obesity from the age of 22 weeks and increase their food intake. The plasma concentrations of insulin, leptin, cholesterol and triglyceride are also increased in obese PrRP-KO mice. Fatty liver, hypertrophied white adipose tissue, decreased uncoupling protein 1 mRNA expression in brown adipose tissue and glucose intolerance were observed in obese PrRP-KO mice. As we reported previously, PrRP stimulates corticotrophin releasing factor and regulates the hypothalamic-pituitary-adrenal axis. Therefore, it is speculated that PrRP regulates both food intake and metabolism as a stress responses. In the present study, we compared blood glucose and plasma glucocorticoid concentrations in PrRP-KO mice, and found that PrRP-KO mice showed higher concentrations of blood glucose and corticosterone compared to wild-type mice after restraint stress. By contrast, there were no difference in c-Fos expression in the paraventricular hypothalamic nucleus and plasma adrenocorticotrophic hormone concentrations between the two groups. These results suggest that the different stress responses as to glucocorticoid secretion may be induced by different responses of the adrenal glands between wild-type and PrRP KO mice. Thus, we conclude that PrRP-KO mice become obese as a result of increased food intake, a change in metabolism, and abnormal stress responses as to glucose concentration and glucocorticoid secretion. PMID- 20298458 TI - Effects of hypoglycaemia on neurotransmitter and hormone receptor gene expression in laser-dissected arcuate neuropeptide Y/agouti-related peptide neurones. AB - Arcuate neuropeptide Y (NPY)/agouti-related pepide (AgRP) neurones regulate energy homeostasis, and express the putative glucosensor, glucokinase (GCK). The present study performed multi-transcriptional profiling of these neurones to characterise NPY, AgRP and GCK gene expression during intermediate insulin induced hypoglycaemia, and to determine whether these transcriptional responses acclimate to repeated insulin dosing. We also examined whether these neurones express insulin, glucocorticoid and oestrogen receptor gene transcripts, and whether the levels of these receptor mRNAs are modified by insulin-induced hypoglycaemia. Individual NPY-immunoreactive neurones were laser-microdissected from the caudal arcuate nucleus after single or serial dosing with neutral protamine Hagedorn insulin (NPH), and evaluated by quantitative real-time reverse transcriptase-polymerase chain reaction for the assessment of neurotransmitter and receptor gene expression. Mean NPY and AgRP mRNA in harvested NPY neurones was unchanged or augmented, respectively, by one NPH dose, although repeated NPH administration up-regulated NPY, whereas AgRP gene transcripts were down regulated. NPH elicited divergent modifications in the ERalpha and ERbeta mRNA content of sampled neurones. ERalpha transcripts were amplified by both acute and chronic NPH-induced hypoglycaemia, whereas ERbeta gene expression was unaltered during a single bout, but suppressed during recurring hypoglycaemia. Glucocorticoid receptor (GR) mRNA levels were increased by a single insulin dose, but unaffected by serial NPH dosing. Insulin receptor-beta chain (InsRb) gene transcripts were insensitive to acute NPH-induced hypoglycaemia, but repeated NPH inhibited this gene transcript. Neither acute nor recurring hypoglycaemia modified GCK mRNA levels in caudal hypothalamic arcuate nucleus (ARH) NPY/AgRP neurones, but baseline GCK transcription was suppressed by the latter. This evidence for the habituation of hypoglycaemic patterns of InsRb, GR and ERbeta gene transcription to serial NPH dosing implies that such treatment may alter reactivity of caudal ARH NPY/AgRP neurones to receptor ligands, and supports the need to determine whether adaptive changes in neuronal sensitivity to insulin, corticosterone and/or oestrogen cause up- versus down-regulation of NPY and AgRP neurotransmission, respectively, by this caudal ARH subpopulation during chronic hypoglycaemia. PMID- 20298460 TI - Herbivory enhances positive effects of plant genotypic diversity. AB - Both plant diversity and vertebrate herbivores can impact plant fitness and ecosystem functioning, however their interactions have not been explicitly tested. We manipulated plant genotypic diversity of the native plant Oenothera biennis and monitored its survivorship and lifetime fitness with and without one of its major vertebrate consumers, white-tailed deer Odocoileus virginianus. Intense but unmanipulated herbivory by meadow voles Microtus pennsylvanicus killed over 70% of nearly 4000 experimental plants. However, plants grown in genotypically diverse patches suffered fewer vole attacks and had higher survival and reproductive output than plants in monoculture. Moreover, positive effects of genotypic diversity were enhanced by the presence of deer, indicating a non additive interaction between diversity and trophic-level complexity. Genetic selection analyses showed that the selective value of ecologically important traits depended on plant diversity and exposure to deer, demonstrating that community complexity can promote fitness through multiple ecologically and evolutionarily important feedbacks. PMID- 20298459 TI - The adaptive brain: Glenn Hatton and the supraoptic nucleus. AB - In December 2009, Glenn Hatton died, and neuroendocrinology lost a pioneer who had done much to forge our present understanding of the hypothalamus and whose productivity had not faded with the passing years. Glenn, an expert in both functional morphology and electrophysiology, was driven by a will to understand the significance of his observations in the context of the living, behaving organism. He also had the wit to generate bold and challenging hypotheses, the wherewithal to expose them to critical and elegant experimental testing, and a way with words that gave his papers and lectures clarity and eloquence. The hypothalamo-neurohypophysial system offered a host of opportunities for understanding how physiological functions are fulfilled by the electrical activity of neurones, how neuronal behaviour changes with changing physiological states, and how morphological changes contribute to the physiological response. In the vision that Glenn developed over 35 years, the neuroendocrine brain is as dynamic in structure as it is adaptable in function. Its adaptability is reflected not only by mere synaptic plasticity, but also by changes in neuronal morphology and in the morphology of the glial cells. Astrocytes, in Glenn's view, were intimate partners of the neurones, partners with an essential role in adaptation to changing physiological demands. PMID- 20298461 TI - Maintenance of genetic variation in immune defense of a freshwater snail: role of environmental heterogeneity. AB - Natural populations often show genetic variation in pathogen resistance, which is paradoxal because natural selection is expected to erode genetic variation in fitness-related traits. Several different factors have been suggested to maintain such variation, but their relative importance is still poorly understood. Here we examined if environmental heterogeneity and genetic trade-offs could contribute to the maintenance of genetic variation in immune function of a freshwater snail Lymnaea stagnalis. We assessed the immunocompetence of snails originating from different families and maintained in different feeding treatments (ad libitum feeding, no food) by measuring the density of circulating hemocytes, phenoloxidase activity, and antibacterial activity of snail hemolymph. Food limitation reduced snail immune function, and we found significant among-family variation in hemocyte concentration and PO activity, but not in antibacterial activity. Interestingly, food availability modified the family-level variation observed in PO activity so that the relative immunocompetence of different snail families changed over environmental conditions (G x E interaction). We found no evidence for genetic trade-offs between snail growth and immune defense nor among immune traits. Thus, our findings support the idea that environmental heterogeneity may promote maintenance of genetic variation in immune defense, but also suggest that different immune traits might not respond similarly to environmental variation. PMID- 20298462 TI - Extreme selection on size in the early lives of fish. AB - Although fitness typically increases with body size and selection gradients on size are generally positive, much of this information comes from terrestrial taxa. In the early life history of fish, there is evidence of selection both for and against larger size, leaving open the question of whether the general pattern for terrestrial taxa is valid for fish. We reviewed studies of size-dependent survival in the early life history of fish and obtained estimates of standardized selection differentials from 40 studies. We found that 77% of estimated selection differentials favored larger size and that the strength of selection was more than five times that seen in terrestrial taxa. Selection decreased with study period duration and initial length, and disruptive selection occurred significantly more frequently than stabilizing selection. Contrary to expectations from Bergmann's rule, selection on size did not increase with latitude. PMID- 20298463 TI - Diversification and persistence at the arid-monsoonal interface: australia-wide biogeography of the Bynoe's gecko (Heteronotia binoei; Gekkonidae). AB - Late Neogene aridification in the Southern Hemisphere caused contractions of mesic biota to refugia, similar to the patterns established by glaciation in the Northern Hemisphere, but these episodes also opened up new adaptive zones that spurred range expansion and diversification in arid-adapted lineages. To understand these dynamics, we present a multilocus (nine nuclear introns, one mitochondrial gene) phylogeographic analysis of the Bynoe's gecko (Heteronotia binoei), a widely distributed complex spanning the tropical monsoon, coastal woodland, and arid zone biomes in Australia. Bayesian phylogenetic analyses, estimates of divergence times, and demographic inferences revealed episodes of diversification in the Pliocene, especially in the tropical monsoon biome, and range expansions in the Pleistocene. Ancestral habitat reconstructions strongly support recent and independent invasions into the arid zone. Our study demonstrates the varied responses to aridification in Australia, including localized persistence of lineages in the tropical monsoonal biome, and repeated invasion of and expansion through newly available arid-zone habitats. These patterns are consistent with those found in other arid environments in the Southern Hemisphere, including the South African succulent karoo and the Chilean lowlands, and highlight the diverse modes of diversification and persistence of Earth's biota during the glacial cycles of the Pliocene and Pleistocene. PMID- 20298464 TI - The evolutionary implications of conflict between parasites with different transmission modes. AB - Understanding the processes that shape the evolution of parasites is a key challenge for evolutionary biology. It is well understood that different parasites may often infect the same host and that this may have important implications to the evolutionary behavior. Here we examine the evolutionary implications of the conflict that arises when two parasite species, one vertically transmitted and the other horizontally transmitted, infect the same host. We show that the presence of a vertically transmitted parasite (VTP) often leads to the evolution of higher virulence in horizontally transmitted parasites (HTPs), particularly if the VTPs are feminizing. The high virulence in some HTPs may therefore result from coinfection with cryptic VTPs. The impact of an HTP on a VTP evolution depends crucially on the nature of the life-history trade-offs. Fast virulent HTPs select for intermediate feminization and virulence in VTPs. Coevolutionary models show similar insights, but emphasize the importance of host life span to the outcome, with higher virulence in both types of parasite in short-lived hosts. Overall, our models emphasize the interplay of host and parasite characteristics in the evolutionary outcome and point the way for further empirical study. PMID- 20298465 TI - Contrasting patterns of phenotypic plasticity in reproductive traits in two great tit (Parus major) populations. AB - Phenotypic plasticity is an important mechanism via which populations can respond to changing environmental conditions, but we know very little about how natural populations vary with respect to plasticity. Here we use random-regression animal models to understand the multivariate phenotypic and genetic patterns of plasticity variation in two key life-history traits, laying date and clutch size, using data from long-term studies of great tits in The Netherlands (Hoge Veluwe [HV]) and UK (Wytham Woods [WW]). We show that, while population-level responses of laying date and clutch size to temperature were similar in the two populations, between-individual variation in plasticity differed markedly. Both populations showed significant variation in phenotypic plasticity (IxE) for laying date, but IxE was significantly higher in HV than in WW. There were no significant genotype-by-environment interactions (GxE) for laying date, yet differences in GxE were marginally nonsignificant between HV and WW. For clutch size, we only found significant IxE and GxE in WW but no significant difference between populations. From a multivariate perspective, plasticity in laying date was not correlated with plasticity in clutch size in either population. Our results suggest that generalizations about the form and cause of any response to changing environmental conditions across populations may be difficult. PMID- 20298466 TI - Population genetic data suggest a role for mosquito-mediated dispersal of West Nile virus across the western United States. AB - After introduction, West Nile virus (WNV) spread rapidly across the western United States between the years 2001 and 2004. This westward movement is thought to have been mediated by random dispersive movements of resident birds. Little attention has been placed on the role of mosquito vectors in virus dispersal across North America. The mosquito vector largely responsible for WNV amplification and transmission of WNV in the western USA is Culex tarsalis. Here we present population genetic data that suggest a potential role for C. tarsalis in the dispersal of WNV across the western USA. Population genetic structure across the species range of C. tarsalis in the USA was characterized in 16 states using 12 microsatellite loci. structure and geneland analyses indicated the presence of three broad population clusters. Barriers to gene flow were resolved near the Sonoran desert in southern Arizona and between the eastern Rocky Mountains and High Plains plateau. Small genetic distances among populations within clusters indicated that gene flow was not obstructed over large portions of the West Coast and within the Great Plains region. Overall, gene flow in C. tarsalis appears to be extensive, potentially mediated by movement of mosquitoes among neighbouring populations and hindered in geographically limited parts of its range. The pattern of genetic clustering in C. tarsalis is congruent with the pattern of invasion of WNV across the western United States, raising the possibility that movement of this important vector may be involved in viral dispersal. PMID- 20298468 TI - Molecular phylogeography of Carapichea ipecacuanha, an amphitropical shrub that occurs in the understory of both semideciduous and evergreen forests. AB - The medicinal shrub Carapichea ipecacuanha (ipecac) is an amphitropic species with three disjunct areas of distribution. In the Brazilian Atlantic and Amazonian ranges, the species was associated mostly with the understory of seasonal semideciduous forests, whereas in the Central American-Colombian range, the species occurred in the understory of moist evergreen forests. We examined the phylogeographic structure of ipecac using chloroplast trnT-trnL and nuclear internal transcribed spacer (ITS) sequences from 120 and 46 specimens, respectively. To complement existing data on root alkaloid profiles, we used high performance liquid chromatography to assess the levels of emetine and cephaeline in 33 specimens from the two Brazilian ranges. The three ranges shared neither nuclear nor chloroplast haplotypes. The phylogeographic structures showed an uneven distribution of genetic diversity, sharp breaks and high levels of genetic differentiation among ranges. Our results suggest that the extant populations are descendents of at least four distinct ancestral lineages. The Atlantic ipecacs showed higher levels of genetic diversity than ipecacs from the other two ranges; it is likely that they derive from two ancestral lineages, with long-term persistence in that region. The Amazonian ipecacs were monomorphic with respect to the ITS and cpDNA sequences, which supports the view that there was a recent expansion from a single parental source after a strong genetic bottleneck. The existence of a fourth distinct lineage is apparent from the high levels of genetic and chemical differentiation that we identified in the Central American Columbian ipecacs. PMID- 20298469 TI - Can small wildlife conservancies maintain genetically stable populations of large mammals? Evidence for increased genetic drift in geographically restricted populations of Cape buffalo in East Africa. AB - The Cape buffalo (Syncerus caffer caffer) is one of the dominant and most widespread herbivores in sub-Saharan Africa. High levels of genetic diversity and exceptionally low levels of population differentiation have been found in the Cape buffalo compared to other African savannah ungulates. Patterns of genetic variation reveal large effective population sizes and indicate that Cape buffalos have historically been interbreeding across considerable distances. Throughout much of its range, the Cape buffalo is now largely confined to protected areas due to habitat fragmentation and increasing human population densities, possibly resulting in genetic erosion. Ten buffalo populations in Kenya and Uganda were examined using seventeen microsatellite markers to assess the regional genetic structure and the effect of protected area size on measures of genetic diversity. Two nested levels of genetic structure were identified: a higher level partitioning populations into two clusters separated by the Victoria Nile and a lower level distinguishing seven genetic clusters, each defined by one or two study populations. Although relatively small geographic distances separate most of the study populations, the level of genetic differentiation found here is comparable to that among pan-African populations. Overall, correlations between conservancy area and indices of genetic diversity suggest buffalo populations inhabiting small parks are showing signs of genetic erosion, stressing the need for more active management of such populations. Our findings raise concerns about the future of other African savannah ungulates with lower population sizes and inferior dispersal capabilities compared with the buffalo. PMID- 20298470 TI - Environmentally induced phenotypes and DNA methylation: how to deal with unpredictable conditions until the next generation and after. AB - Organisms often respond to environmental changes by producing alternative phenotypes. Epigenetic processes such as DNA methylation may contribute to environmentally induced phenotypic variation by modifying gene expression. Changes in DNA methylation, unlike DNA mutations, can be influenced by the environment; they are stable at the time scale of an individual and present different levels of heritability. These characteristics make DNA methylation a potentially important molecular process to respond to environmental change. The aim of this review is to present the implications of DNA methylation on phenotypic variations driven by environmental changes. More specifically, we explore epigenetic concepts concerning phenotypic change in response to the environment and heritability of DNA methylation, namely the Baldwin effect and genetic accommodation. Before addressing this point, we report major differences in DNA methylation across taxa and the role of this modification in producing and maintaining environmentally induced phenotypic variation. We also present the different methods allowing the detection of methylation polymorphism. We believe this review will be helpful to molecular ecologists, in that it highlights the importance of epigenetic processes in ecological and evolutionary studies. PMID- 20298471 TI - Recurrent nuclear DNA introgression accompanies chloroplast DNA exchange between two eucalypt species. AB - Numerous studies within plant genera have found geographically structured sharing of chloroplast (cp) DNA among sympatric species, consistent with introgressive hybridization. Current research is aimed at understanding the extent, direction and significance of nuclear (nr) DNA exchange that accompanies putative cpDNA exchange. Eucalyptus is a complex tree genus for which cpDNA sharing has been established between multiple species. Prior phylogeographic analysis has indicated cpDNA introgression into the widespread forest species Eucalyptus globulus from its rare congener E. cordata. In this study, we use AFLP markers to characterize corresponding nrDNA introgression, on both a broad and fine spatial scale. Using 388 samples we examine (i) the fine-scale spatial structure of cp and nrDNA introgression from E. cordata into E. globulus at a site in natural forest and (ii) broad-scale patterns of AFLP marker introgression at six additional mixed populations. We show that while E. globulus and E. cordata retain strongly differentiated nuclear gene pools overall, leakage of nrDNA occurs at mixed populations, with some AFLP markers being transferred to E. globulus recurrently at different sites. On the fine scale, different AFLP fragments show varying distances of introgression into E. globulus, while introgression of cpDNA is extensive. The frequency of E. cordata markers in E. globulus is correlated with spatial proximity to E. cordata, but departs from expectations based on AFLP marker frequency in E. cordata, indicating that selection may be governing the persistence of introgressed fragments in E. globulus. PMID- 20298472 TI - Six quantitative trait loci influence task thresholds for hygienic behaviour in honeybees (Apis mellifera). AB - Honeybee hygienic behaviour provides colonies with protection from many pathogens and is an important model system of the genetics of a complex behaviour. It is a textbook example of complex behaviour under simple genetic control: hygienic behaviour consists of two components--uncapping a diseased brood cell, followed by removal of the contents--each of which are thought to be modulated independently by a few loci of medium to large effect. A worker's genetic propensity to engage in hygienic tasks affects the intensity of the stimulus required before she initiates the behaviour. Genetic diversity within colonies leads to task specialization among workers, with a minority of workers performing the majority of nest-cleaning tasks. We identify three quantitative trait loci that influence the likelihood that workers will engage in hygienic behaviour and account for up to 30% of the phenotypic variability in hygienic behaviour in our population. Furthermore, we identify two loci that influence the likelihood that a worker will perform uncapping behaviour only, and one locus that influences removal behaviour. We report the first candidate genes associated with engaging in hygienic behaviour, including four genes involved in olfaction, learning and social behaviour, and one gene involved in circadian locomotion. These candidates will allow molecular characterization of this distinctive behavioural mode of disease resistance, as well as providing the opportunity for marker-assisted selection for this commercially significant trait. PMID- 20298473 TI - Historical male-mediated introgression in horseshoe bats revealed by multilocus DNA sequence data. AB - Instances of hybridization between mammalian taxa in the wild are rarely documented. To test for introgression between sibling species of horseshoe bat (Rhinolophus yunanensis and R. pearsoni) and two subspecies of the latter (R. p. pearsoni and R. p. chinensis), we sequenced two mtDNA and two ncDNA markers in individuals sampled from multiple localities within their overlapping ranges. The interspecific mtDNA gene tree corresponded to the expected taxonomic divisions, and coalescent-based analyses suggested divergence occurred around 4 MYA. However, these relationships strongly conflicted with those recovered from two independent nuclear gene trees, in which R. yunanensis clustered with R. p. pearsoni to the exclusion of R. p. chinensis. This geographically widespread discordance is best explained by large-scale historical introgression of ncDNA from R. yunanensis to R. pearsoni by male-mediated exchange in mixed species colonies during Pleistocene glacial periods, when ranges may have contracted and overlapped more than at present. Further species tree-gene tree conflicts were detected between R. p. pearsoni and R. p. chinensis, also indicating past and/or current introgression in their overlapping regions. However, here the patterns point to asymmetric mtDNA introgression without ncDNA introgression. Analyses of coalescence times indicate this exchange has occurred subsequent to the divergence of these subspecies from their common ancestor. Our work highlights the importance of using multiple data sets for reconstructing phylogeographic histories and resolving taxonomic relationships. PMID- 20298476 TI - Expression of diagnostic neuronal markers and outcome in glioblastoma. AB - BACKGROUND: High-grade gliomas featuring giant cells, often demonstrate immunoreactivity for neuronal markers, a finding prognostically significant according to some studies. We investigated this event in glioblastomas (GBM). METHODS: Immunoexpression for synaptophysin, neurofilament protein, neuronal nuclear antigen, chromogranin and glial fibrillary acidic protein was analysed in 82 GBM including 11 fibrillary, 8 gemistocytic, 40 giant cell and 23 small cell examples. Survival was compared between tumours exhibiting (GBMpos) or lacking (GBMneg) neuronal markers and also between tumours expressing only one vs. two or more neuronal markers. RESULTS: Forty-five of the 82 tumours (54.8%) including 5 fibrillary, 5 gemistocytic, 30 giant cell and 5 small cell GBMs expressed at least one neuronal marker, synaptophysin being the most frequent (96%). There was no statistically significant difference in survival between GBMpos and GBMneg tumours, all cytologic subtypes combined (P = 0.22). The same was true when cytologic categories were compared. When only GBMpos tumours were analysed, there was a marginally significant difference in outcome between tumours positive for one vs. multiple markers (P = 0.05). This difference was influenced primarily by giant cell GBMs among which the survival time was significantly shorter in the multiple vs. single marker category (median 123 vs. 295 days, P = 0.014). This difference was not observed in the other GBM cell types. Ultrastructurally, rare neurosecretory granules in glial filament-rich cells were identified in one of four tumours studied. CONCLUSIONS: Neuronal marker expression is a frequent feature of GBM. Its prognostic significance is limited to the giant cell GBMs expressing two or more neuronal markers, these being associated with shorter survival. PMID- 20298477 TI - Na+/H+ antiporters are differentially regulated in response to NaCl stress in leaves and roots of Mesembryanthemum crystallinum. AB - Salinity tolerance in plants involves controlled Na(+) transport at the site of Na(+) accumulation and intracellular Na(+) compartmentation. The focus of this study was the identification and analysis of the expression of Na(+)/H(+) antiporters in response to NaCl stress in one particular plant, the facultative halophyte Mesembryanthemum crystallinum Na(+)/H(+) antiporters of M. crystallinum were cloned by RACE-PCR from total mRNA of leaf mesophyll cells. Functional complementation of Saccharomyces cerevisiae and Escherichia coli mutants was performed. The kinetics of changes in the expression of antiporters were quantified by real-time PCR in leaves and roots. Five Na(+)/H(+) antiporters (McSOS1, McNhaD, McNHX1, McNHX2 and McNHX3) were cloned, representing the entire set of these transporters in M. crystallinum. The functionality of McSOS1, McHX1 and McNhaD was demonstrated in complementation experiments. Quantitative analysis revealed a temporal correlation between salt accumulation and expression levels of genes in leaves, but not in roots, which was most pronounced for McNhaD. Results suggest a physiological role of McSOS1, McNhaD and McNHX1 in Na(+) compartmentation during plant adaptation to high salinity. The study also provides evidence for salt-induced expression and function of the Na(+)/H(+) antiporter McNhaD in chloroplasts and demonstrates that the chloroplast is one of the compartments involved in the response of cells to salt stress. PMID- 20298478 TI - Callose implication in stomatal opening and closure in the fern Asplenium nidus. AB - The involvement of callose in the mechanism of stomatal pore opening and closing in the fern Asplenium nidus was investigated by examination of the pattern of callose deposition in open and closed stomata, and by examination of the effects of callose degradation and inhibition or induction of callose synthesis in stomatal movement. Callose was identified with aniline blue staining and a callose antibody and degraded via beta-1,3-D-glucanase. Callose synthesis was inhibited with 2-deoxy-D-glucose and induced by coumarin or dichlobenil. Stomatal pore opening and closing were assessed by estimation of the stomatal pore width. The open stomata entirely lacked callose, while the closed ones displayed distinct radial fibrillar callose arrays in the external periclinal walls. The latter displayed local bending at the region of callose deposition, a deformation that was absent in the open stomata. Both callose degradation and inhibition of callose synthesis reduced the stomatal ability to open in white light and close in darkness. By contrast, callose synthesis induction considerably improved stomatal pore opening and reduced stomatal closure in same conditions. The present data revealed that: during stomatal closure the external periclinal guard cell walls experience a strong mechanical stress, probably triggering callose synthesis; and that callose participates in stomatal movement. PMID- 20298479 TI - A novel phototropic response to red light is revealed in microgravity. AB - The aim of this study was to investigate phototropism in plants grown in microgravity conditions without the complications of a 1-g environment. Experiments performed on the International Space Station (ISS) were used to explore the mechanisms of both blue-light- and red-light-induced phototropism in plants. This project utilized the European Modular Cultivation System (EMCS), which has environmental controls for plant growth as well as centrifuges for gravity treatments used as a 1-g control. Images captured from video tapes were used to analyze the growth, development, and curvature of Arabidopsis thaliana plants that developed from seed in space. A novel positive phototropic response to red light was observed in hypocotyls of seedlings that developed in microgravity. This response was not apparent in seedlings grown on Earth or in the 1-g control during the space flight. In addition, blue-light-based phototropism had a greater response in microgravity compared with the 1-g control. Although flowering plants are generally thought to lack red light phototropism, our data suggest that at least some flowering plants may have retained a red light sensory system for phototropism. Thus, this discovery may have important implications for understanding the evolution of light sensory systems in plants. PMID- 20298480 TI - Relationships between carbonyl sulfide (COS) and CO2 during leaf gas exchange. AB - *Carbonyl sulfide (COS) exchange in C(3) leaves is linked to that of CO(2), providing a basis for the use of COS as a powerful tracer of gross CO(2) fluxes between plants and the atmosphere, a critical element in understanding the response of the land biosphere to global change. *Here, we carried out controlled leaf-scale gas-exchange measurements of COS and CO(2) in representative C(3) plants under a range of light intensities, relative humidities and temperatures, CO(2) and COS concentrations, and following abscisic acid treatments. *No 'respiration-like' emission of COS or detectable compensation point, and no cross inhibition effects between COS and CO(2) were observed. The mean ratio of COS to CO(2) assimilation flux rates, A(s)/A(c), was c. 1.4 pmol micromol(-1) and the leaf relative uptake (assimilation normalized to ambient concentrations, (A(s)/A(c))(C(a)(c)/C(a)(s))) was 1.6-1.7 across species and conditions, with significant deviations under certain conditions. Stomatal conductance was enhanced by increasing COS, which was possibly mediated by hydrogen sulfide (H(2)S) produced from COS hydrolysis, and a correlation was observed between A(s) and leaf discrimination against C(18)OO. *The results provide systematic and quantitative information necessary for the use of COS in photosynthesis and carbon-cycle research on the physiological to global scales. PMID- 20298481 TI - Tissue-level leaf toughness, but not lamina thickness, predicts sapling leaf lifespan and shade tolerance of tropical tree species. AB - Leaf toughness is thought to enhance physical defense and leaf lifespan. Here, we evaluated the relative importance of tissue-level leaf traits vs lamina thickness, as well as their ontogenetic changes, for structure-level leaf toughness and regeneration ecology of 19 tropical tree species. We measured the fracture toughness of the laminas and veins of sapling leaves with shearing tests, and used principal component analysis and structural equation modeling to evaluate the multivariate relationships among traits that contribute to leaf toughness and their links to ecological performance traits. Tissue traits (density and fracture toughness of lamina and vein) were correlated positively with each other, but independent of lamina thickness. The tissue traits and lamina thickness contributed additively to the structure-level toughness (leaf mass per area and work-to-shear). Species with dense and tough leaves as saplings also had dense and tough leaves as seedlings and adults. The patterns of ontogenetic change in trait values differed between the seedling-to-sapling and sapling-to-adult transitions. The fracture toughness and tissue density of laminas and veins, but not the lamina thickness, were correlated positively with leaf lifespan and sapling survival, and negatively with herbivory rate and sapling regeneration light requirements, indicating the importance of tissue level leaf traits. PMID- 20298482 TI - Effects of fusicoccin on ion fluxes in guard cells. AB - The pharmacology has been further investigated of the two transport systems mediating potassium (rubidium) (K(+)(Rb(+))) release from the guard cell vacuole, responsible, respectively, for the resting efflux and abscisic acid (ABA)-induced transient stimulation of efflux, and for the transient stimulation induced by hypotonic treatment. Here, the effects of fusicoccin and of butyrate-induced cytoplasmic acidification on (86)Rb efflux were measured in isolated guard cells of Commelina communis. Fusicoccin (10 microM) inhibited the resting efflux at the tonoplast and the ABA-induced transient, but had no effect on the hypotonic transient. All three processes were inhibited by cytoplasmic acidification. Fusicoccin did not inhibit efflux at the plasmalemma. As the hypotonic response is inhibited by cytoplasmic acidification but not by fusicoccin, the effect of fusicoccin on the resting efflux and ABA response must be direct, and not the result of fusicoccin-induced cytoplasmic acidification. The collected tonoplast efflux properties resemble those of TPC1 (two-pore channel) rather than TPK1 (two pore K channel). The flux and TPC1 are both activated by Ca(2+), but inhibited by phenylarsine oxide and by cytoplasmic acidification. The flux is inhibited by fusicoccin. TPC1 is inhibited by 14-3-3 proteins and has the C-terminal sequence STSDT, a type III binding site for 14-3-3 proteins, of the kind involved in fusicoccin binding. PMID- 20298483 TI - An endoplasmic reticulum response pathway mediates programmed cell death of root tip induced by water stress in Arabidopsis. AB - Drought induces root death in plants; however, the nature and characteristics of root cell death and its underlying mechanisms are poorly understood. Here, we provide a systematic analysis of cell death in the primary root tips in Arabidopsis during water stress. Root tip cell death occurs when high water deficit is reached. The dying cells were first detected in the apical meristem of the primary roots and underwent active programmed cell death (PCD). Transmission electron microscopic analysis shows that the cells undergoing induced death had unambiguous morphological features of autophagic cell death, including an increase in vacuole size, degradation of organelles, and collapse of the tonoplast and the plasma membrane. The results suggest that autophagic PCD occurs as a response to severe water deficit. Significant accumulation of reactive oxygen species (ROS) was detected in the stressed root tips. Expression of BAX inhibitor-1 (AtBI1) was increased in response to water stress, and atbi1-1 displayed accelerated cell death, indicating that AtBI1 and the endoplasmic reticulum (ER) stress response pathway both modulate water stress-induced PCD. These findings form the basis for further investigations into the mechanisms underlying the PCD and its role in developmental plasticity of root system architecture and subsequent adaptation to water stress. PMID- 20298484 TI - Birch (Betula spp.) leaves adsorb and re-release volatiles specific to neighbouring plants--a mechanism for associational herbivore resistance? AB - Plant-emitted semi-volatile compounds have low vaporization rates at 20-25 degrees C and may therefore persist on surfaces such as plant foliage. The passive adsorption of arthropod-repellent semi-volatiles to neighbouring foliage could convey associational resistance, whereby a plant's neighbours reduce damage caused by herbivores. We found that birch (Betula spp.) leaves adsorb and re release the specific arthropod-repelling C(15) semi-volatiles ledene, ledol and palustrol produced by Rhododendron tomentosum when grown in mixed association in a field setup. In a natural habitat, a higher concentration of ledene was released from birches neighbouring R. tomentosum than from birches situated > 5 m from R. tomentosum. Emission of alpha-humulene, a sesquiterpene synthesized by both Betula pendula and R. tomentosum, was also increased in R. tomentosum neighbouring B. pendula. In assessments for associational resistance, we found that the polyphagous green leaf weevils (Polydrusus flavipes) and autumnal moth (Epirrita autumnata) larvae both preferred B. pendula to R. tomentosum. P. flavipes also preferred birch leaves not exposed to R. tomentosum to leaves from mixed associations. In the field, a reduction in Euceraphis betulae aphid density occurred in mixed associations. Our results suggest that plant/tree species may be protected by semi-volatile compounds emitted by a more herbivore-resistant heterospecific neighbour. PMID- 20298485 TI - Comparing arbuscular mycorrhizal communities of individual plants in a grassland biodiversity experiment. AB - Plants differ greatly in the soil organisms colonizing their roots. However, how soil organism assemblages of individual plant roots can be influenced by plant community properties remains poorly understood. We determined the composition of arbuscular mycorrhizal fungi (AMF) in Jacobaea vulgaris plants, using terminal restriction fragment length polymorphism (T-RFLP). The plants were collected from an experimental field site with sown and unsown plant communities. Natural colonization was allowed for 10 yr in sown and unsown plots. Unsown plant communities were more diverse and spatially heterogeneous than sown ones. Arbuscular mycorrhizal fungi diversity did not differ between sown and unsown plant communities, but there was higher AMF assemblage dissimilarity between individual plants in the unsown plant communities. When we grew J. vulgaris in field soil that was homogenized after collection in order to rule out spatial variation, no differences in AMF dissimilarity between sown and unsown plots were found. Our study shows that experimental manipulation of plant communities in the field, and hence plant community assembly history, can influence the AMF communities of individual plants growing in those plant communities. This awareness is important when interpreting results from field surveys and experimental ecological studies in relation to plant-symbiont interactions. PMID- 20298486 TI - Biological stoichiometry of plant production: metabolism, scaling and ecological response to global change. AB - Biological stoichiometry theory considers the balance of multiple chemical elements in living systems, whereas metabolic scaling theory considers how size affects metabolic properties from cells to ecosystems. We review recent developments integrating biological stoichiometry and metabolic scaling theories in the context of plant ecology and global change. Although vascular plants exhibit wide variation in foliar carbon:nitrogen:phosphorus ratios, they exhibit a higher degree of 'stoichiometric homeostasis' than previously appreciated. Thus, terrestrial carbon:nitrogen:phosphorus stoichiometry will reflect the effects of adjustment to local growth conditions as well as species' replacements. Plant stoichiometry exhibits size scaling, as foliar nutrient concentration decreases with increasing plant size, especially for phosphorus. Thus, small plants have lower nitrogen:phosphorus ratios. Furthermore, foliar nutrient concentration is reflected in other tissues (root, reproductive, support), permitting the development of empirical models of production that scale from tissue to whole-plant levels. Plant stoichiometry exhibits large-scale macroecological patterns, including stronger latitudinal trends and environmental correlations for phosphorus concentration (relative to nitrogen) and a positive correlation between nutrient concentrations and geographic range size. Given this emerging knowledge of how plant nutrients respond to environmental variables and are connected to size, the effects of global change factors (such as carbon dioxide, temperature, nitrogen deposition) can be better understood. PMID- 20298487 TI - Disruption of plant carotenoid biosynthesis through virus-induced gene silencing affects oviposition behaviour of the butterfly Pieris rapae. AB - Optical plant characteristics are important cues to plant-feeding insects. In this article, we demonstrate for the first time that silencing the phytoene desaturase (PDS) gene, encoding a key enzyme in plant carotenoid biosynthesis, affects insect oviposition site selection behaviour. Virus-induced gene silencing employing tobacco rattle virus was used to knock down endogenous PDS expression in three plant species (Arabidopsis thaliana, Brassica nigra and Nicotiana benthamiana) by its heterologous gene sequence from Brassica oleracea. We investigated the consequences of the silencing of PDS on oviposition behaviour by Pieris rapae butterflies on Arabidopsis and Brassica plants; first landing of the butterflies on Arabidopsis plants (to eliminate an effect of contact cues); first landing on Arabidopsis plants enclosed in containers (to eliminate an effect of volatiles); and caterpillar growth on Arabidopsis plants. Our results show unambiguously that P. rapae has an innate ability to visually discriminate between green and variegated green-whitish plants. Caterpillar growth was significantly lower on PDS-silenced than on empty vector control plants. This study presents the first analysis of PDS function in the interaction with an herbivorous insect. We conclude that virus-induced gene silencing is a powerful tool for investigating insect-plant interactions in model and nonmodel plants. PMID- 20298488 TI - Molecular detection of avian influenza virus but not West Nile virus in wild birds in northern Turkey. AB - In this study, a total of 402 samples (173 cloacal swab samples, 169 tracheal swab samples and 60 organ pools including the lung, spleen, liver, trachea and brain) obtained from 27 different wild avian species from Kizilirmak delta and the adjacent wetlands in northern Turkey were surveyed for the presence of RNA from Avian influenza virus (AIV) and West Nile virus (WNV) by Taqman-based real time reverse transcriptase-polymerase chain reaction assay. No WNV genomic RNA was detected in any sample. In contrast, AIV RNA was found in two of 402 samples (0.49%). PMID- 20298489 TI - Avian influenza A virus monitoring in wild birds in Bavaria: occurrence and heterogeneity of H5 and N1 encoding genes. AB - To define avian influenza virus prevalence in wild birds in Bavaria, 12,930 tracheal, cloacal swabs or tissue samples from various waterfowl species were screened between January 2006 and December 2007. In 291 (2.3%) birds, genomes of influenza A viruses were detected by reverse transcription real-time PCR (rRT PCR) targeting the matrix protein genes. Furthermore, solitary H5 hemagglutinin or N1 neuraminidase encoding genes were identified in 35 (0.3%) apparently healthy birds; whereas highly pathogenic (HPAI) H5N1 virus genomes were only diagnosed in dead wild birds (n = 93; 0.7%) found across this federal state region. In this study, multiple import events for H5N1 viruses were confirmed during 2006 and 2007. In addition, our findings argue against an existing HPAI H5N1 reservoir in aquatic birds in Bavaria. By contrast, phylogenetic analyses of the H5 or N1 sequences of low pathogenic avian influenza (LPAI) viruses revealed a marked diversity and multiple genetic lineages. This diversity of LPAI H5 and N1 subtype components indicates the existence of LPAI HA and NA gene pools which differ from the Bavarian HPAI H5N1. Moreover, the hemagglutinin amino acid differences between LPAI H5 viruses of a western European genotypic lineage observed in wild birds suggest a continuous evolution of LPAI viruses in Bavaria. PMID- 20298490 TI - Serological surveillance of influenza A virus infection in swine populations in Fujian province, China: no evidence of naturally occurring H5N1 infection in pigs. AB - Several highly pathogenic H5N1 avian influenza viruses were isolated from swine populations in Fujian Province, China, since 2001. Because it is thought that H5N1 infection in pigs might result in virus adaptation to humans, we surveyed swine populations in Fujian Province in 2004 and 2007 for serological evidence of the infection. Twenty-five pig farms covering all nine administrative districts of Fujian Province were sampled and a total of 1407 serum specimens were collected. The haemagglutination inhibition (HI) tests revealed no evidence of H5 infection and only a few cases of H9 infection. The negative results for H5 infection were further verified by micro-neutralization tests. By contrast, H1 influenza virus infections were prevalent in swine in both surveys according to the results of enzyme-linked immunosorbent assay (ELISA). The H3 infection rate was reduced dramatically in 2007 compared with 2004, when examined by HI and ELISA. In summary, the results imply that the swine populations in Fujian Province had not been affected greatly by the H5N1 avian influenza virus, given that there is no serological evidence that H5N1 influenza virus has infected the pig populations. The reported isolates represent only sporadic cases. PMID- 20298491 TI - Overall survival, prognostic factors, and repeated surgery in a consecutive series of 516 patients with glioblastoma multiforme. AB - OBJECTIVES: To study overall survival (OS), prognostic factors, and repeated surgery in glioblastoma multiforme (GBM). MATERIAL AND METHODS: Retrospective study of 516 consecutive adult patients who underwent primary surgery for a GBM in year 2003-2008. RESULTS: Median age at primary surgery was 63.7 years (range 18.0-88.0). Median OS was 9.9 months. Age > 60 years, poor preoperative ECOG score, bilateral tumor, biopsy rather than resection, and no temozolomide chemoradiotherapy were negative risk factors. Repeat surgery was performed in 65 patients (13%). Median time between first and second surgery was 7 months. Indications for second surgery were increasing neurological deficits (35.4%), raised ICP (33.8%), asymptomatic but reoperated because of tumor progression verified on MRI (20.0%), and epileptic seizures (11%). Patients who underwent repeated surgery had longer OS; 18.4 months vs 8.6 months (P < 0.001). CONCLUSIONS: OS for adult GBM patients was 9.9 months. Negative prognostic factors were increasing age, poor neurological function, bilateral tumor involvement, biopsy instead of resection, and RT alone compared to temozolomide chemoradiotherapy. Our rate of repeated surgery for GBM was 13% and the main indications for second surgery were raised ICP and increasing neurological deficits. In a carefully selected group of patients, repeat surgery significantly prolongs OS. PMID- 20298492 TI - Sleep habits and sleep complaints in Austria: current self-reported data on sleep behaviour, sleep disturbances and their treatment. AB - OBJECTIVES: To acquire current information on sleep habits, disturbances and treatment options in the adult population of Austria and compare results with previously collected data. MATERIALS AND METHODS: A representative sample of the Austrian population (women: n = 522, men: n = 478). RESULTS: Seventy-five percent reported daily sleep-duration between 6 and 8 h. In 76%, sleep latency was <30 min, 15% described difficulties in sleep maintenance. Longer sleep on weekends was prevalent in 54%, 23% took a nap. Concerning sleep environment, 31% reported sleeping alone; the rest had a constant or occasional bed partner. Sleep disturbances such as sleep disruption or prolonged sleep latency were reported by 18%. Predominant symptoms included snoring/apneas (22%), nightmares (22%) and restless legs (21%). Daytime tiredness was reported by 17% and sleepiness by 20%. Twenty-four percent did not take treatment. Only 7% asked for medical help: 96% consulted their physician; 47% tried to change their way of living. Sleep promoting drugs were taken by 7%. Sleep improving measures were: sleep promoters (45%), general measures (20%), consultation of general practitioner (20%), psychotherapy (6%), and technical tools (3%). Comparison with a dataset of 1993 revealed only a slight increase in short sleepers and a slight decrease in long sleepers. CONCLUSIONS: Subjectively reported sleep disorders proved to be relatively stable between 1993 and 2007. PMID- 20298493 TI - Metabolic differences between male and female adolescents with non-alcoholic fatty liver disease, as detected by ultrasound. AB - BACKGROUND: Age, developmental stage and gender are risk factors for paediatric non-alcoholic fatty liver disease (NAFLD). AIMS: The aim of this study was to identify differences in clinical or laboratory variables between sexes in adolescents with NAFLD. METHODOLOGY: Ninety obese adolescents including 36 males and 54 females were evaluated. Inclusion criteria for this study were a Body Mass Index above the 95th percentile, as set forth by the National Center for Health Statistics, and an age of 10-19 years. A clinical and laboratory evaluation was conducted for all adolescents. RESULTS: The variables that were found to be predictive of NAFLD in adolescence were visceral fat, Aminotransferase, Gamma Glutamyl Transferase, triglyderides, cholesterol and LDL-cholesterol. We also observed that cholesterol and LDL-cholesterol variables were influenced by gender, i.e. there was a significant statistical difference in the values of these variables between male and female adolescents. With regard to cholesterol serum concentrations, the risk was 6.99 times greater for females, compared with 1.2 times for males; and for LDL-cholesterol serum concentrations the risk was 8.15 times greater for females, compared with and 1.26 times for males. CONCLUSION: Female adolescents with NAFLD showed a significantly different metabolic behaviour than males. PMID- 20298494 TI - Motor function and methylphenidate effect in children with attention deficit hyperactivity disorder. AB - AIM: Hyperactivity, impulsivity and poor attention are the core problems of ADHD and central stimulant medication is the preferred treatment. Many children with ADHD also display motor problems. The present study investigated the presence of motor problems in subjects who showed positive response to central stimulants on ADHD symptoms, compared with non-responders. METHOD: This is a retrospective study of 73 children diagnosed ADHD, aged 5-17 years, who had been assessed with parts of the 'Motor Function Neurological Assessment' (MFNU) and evaluated with regard to effect of central stimulant medication. The sample was divided into two subgroups based on the responses to methylphenidate: Medicine responders and Non medicine responders. RESULTS: Stimulant responders showed significantly more motor problems than the non-responders on all sub-tests and on the total problem score of the MFNU. Motor problems were present both in younger (age 5-10 years) and older (11-17 years) stimulant responders. There were no gender differences in motor performance. CONCLUSION: Our findings indicate that the probability of positive effect of central stimulants on core problems of ADHD is higher when motor problems are present in addition to ADHD symptoms, than when motor problems are absent. PMID- 20298495 TI - Vaccination coverage of Greek paediatric healthcare workers against seasonal and A/H1N1 influenza. PMID- 20298496 TI - Adalimumab sustains clinical remission and overall clinical benefit after 2 years of therapy for Crohn's disease. AB - BACKGROUND: In the randomized, double-blind, placebo-controlled CHARM trial, adalimumab was more effective than placebo in maintaining clinical remission for patients with moderate-to-severe Crohn's disease (CD) through 56 weeks. AIM: To substantiate the long-term safety and clinical benefits of adalimumab through 2 years of therapy in CHARM and its open-label extension (ADHERE). METHODS: Patients entering ADHERE on blinded therapy received adalimumab 40 mg every other week (eow). Patients who had already moved to open-label adalimumab eow or weekly in CHARM continued their regimens. Data were analysed by originally randomized treatment group at CHARM baseline (adalimumab 40 mg eow, adalimumab 40 mg weekly, or placebo), regardless of whether patients entered ADHERE or received open-label adalimumab (eow or weekly). RESULTS: After up to 2 years of therapy, 37.6%, 41.9% and 49.8% of patients originally randomized to placebo, adalimumab eow and adalimumab weekly, respectively, were in clinical remission. All groups experienced sustained improvements on the Inflammatory Bowel Disease Questionnaire. Decreasing hazard rates for both all-cause and CD-related hospitalizations were observed over time. Over a 2-year period, the rates of serious adverse events and malignancies (33.3 and 1.1 events/100-patient-years respectively) were similar to those observed during the overall adalimumab CD clinical development programme. CONCLUSIONS: Adalimumab demonstrated sustained maintenance of clinical remission, improvements in quality of life and reductions in hospitalization during long-term treatment for CD, with no new safety concerns identified. PMID- 20298497 TI - Clinical trial: the effects of certolizumab pegol therapy on work productivity in patients with moderate-to-severe Crohn's disease in the PRECiSE 2 study. AB - BACKGROUND: The effect of certolizumab pegol on employment status and work productivity has not been previously assessed. AIM: To assess the impact of treatment with certolizumab pegol, the only PEGylated, Fab' TNF antagonist, on work productivity in patients with active Crohn's disease (CD) from the PRECiSE 2 study. METHODS: Patients (n = 668) with active disease [CD activity index (CDAI) score of 220-450] were treated with open-label subcutaneous certolizumab pegol 400 mg (week 0, 2, 4). Responders (n = 425) (> or = 100-point decrease in CDAI from baseline) were randomized to receive certolizumab pegol 400 mg or placebo every 4 weeks until week 24, with final evaluation at week 26. Patients completed the Work Productivity and Activity Impairment for CD questionnaire (WPAI:CD) and the Inflammatory Bowel Disease Questionnaire (IBDQ) at weeks 0, 6, 16 and 26 and at the withdrawal visit. RESULTS: Work productivity improved following induction with certolizumab pegol. Between week 6 and 26, certolizumab pegol-treated patients experienced significant improvement in work productivity compared with placebo recipients (11% and 10% overall improvement in work and activity impairment, respectively). During the maintenance phase, impairments in productivity and activities due to CD were significantly less in the certolizumab pegol group than in the placebo group. CONCLUSION: Induction and maintenance therapy with certolizumab pegol significantly improved the work productivity of patients with active CD compared with those in the placebo group. PMID- 20298498 TI - The challenge of uncorrected refractive error: driving the agenda of the Durban Declaration on refractive error and service development. AB - The purpose of this article is to highlight the challenge of uncorrected refractive error globally, as well as to discuss recent advocacy successes and innovative programs designed to address the need for broader refractive error service development, particularly in developing countries. The World Health Organization's VISION 2020: The Right to Sight program first posed the challenge to national governments to give priority to strategies and resources targeted towards avoidable causes of blindness and visual impairment, so that these unnecessary forms of blindness or visual impairment can be eliminated globally by the year 2020. The blindness prevention community is challenged to increase in scale its initiatives, which support the attainment of VISION 2020: The Right to Sight goals primarily and the United Nation's Millennium Development Goals indirectly. The Durban Declaration on Refractive Error and Service Development was the outcome of a meeting of eye-care professionals, researchers, governments, civil society and industry in March 2007 and still stands as a guiding document to the blindness prevention community for the elimination of avoidable blindness due to uncorrected refractive error. PMID- 20298499 TI - The development and preliminary evaluation of a new Mycobacterium tuberculosis vaccine comprising Ag85b, HspX and CFP-10:ESAT-6 fusion protein with CpG DNA and aluminum hydroxide adjuvants. AB - Ag85b and HspX of Mycobacterium tuberculosis (Mtb) (H37Rv) were expressed and purified in this study. These two proteins were combined with another fusion protein CFP-10:ESAT-6 (C/E) (Ag), then mixed with the adjuvants CpG DNA and aluminum hydroxide and used to vaccinate mice and guinea pigs challenged with Mtb (H37Rv). The number of spleen lymphocytes secreting Ag85b, HspX and C/E-specific interferon-gamma were significantly higher in the Ag+Al+CpG group than in the Ag and CpG groups. The combination of Ag, Al and CpG induced the highest concentrations of anti-Ag85b, anti-HspX and anti-C/E immunoglobulin G in mouse serum. Mouse peritoneal macrophages from the Ag+Al+CpG group secreted significantly higher levels of interleukin-12 compared with macrophages from the other groups. The total mean liver, lung and spleen lesion scores and bacterial loads in the spleen in guinea pigs vaccinated with Ag+Al+CpG were lower than those of the other groups, but no significant difference was found. These results show that the mixture of Ag85b, HspX and C/E with a combination of CpG and aluminum adjuvants can induce both humoral and cellular immune responses in mice, whereas it plays only a small role in the control of disease progression in guinea pigs challenged with Mtb. PMID- 20298500 TI - Biofilms in chronic bacterial prostatitis (NIH-II) and in prostatic calcifications. AB - The prevalence of inflammatory conditions of the prostate gland is increasing. In Italy, there is a high incidence of prostatitis (13.3%), also accompanied by prostatic calcifications. Cat NIH-II chronic bacterial prostatitis (CBPs) are the most frequent. Their aetiology theoretically involves the whole range of bacterial species that are able to form biofilms and infect prostate cells. The aim of our study was to isolate potential biofilm-producing bacteria from CBP patients, to evaluate their ability to produce in vitro biofilms, and to characterize intraprostatic bacteria and prostatic calcifications using scanning electron microscopy. The 150 clinical bacterial strains isolated from chronic prostatitis NIH-II patients were: 50 Enterococcus faecalis; 50 Staphylococcus spp.; 30 Escherichia coli; 20 gram-negative miscellanea. Quantitative assay of biofilm production and adhesion was performed according to the classic Christensen microwell assay. Isolates were classified as nonproducers, weak, moderate or strong producers. The majority of E. coli, gram-negative bacteria, Staphylococci and Enterococci strains were strong or medium producers: 63-30%, 75 15%, 46-36%, and 58-14%, respectively. Prostatic calcifications consisted of bacteria-like forms similar to the species isolated from biological materials and calcifications of patients. Our study proves, for the first time, that bacterial strains able to produce biofilms consistently are present in CBP. Additionally, prostatic calcifications are biofilm-related. PMID- 20298501 TI - Bacterial diversity, pigments and nitrogen fixation of biological desert crusts from the Sultanate of Oman. AB - Biological desert crusts are relatively common in the arid deserts of the Sultanate of Oman; however, little is known about their microbial community composition and role in soil fertilization. We compared three crusts from geographically different locations for their soil texture, bacterial community structure, pigment composition and nitrogenase activity. The crusts were growing on alkaline (pH 7.6-8.7) loamy sand and silty loam soils. Microscopically, Microcoleus vaginatus was the most abundant cyanobacterium, but Nostoc and Scytonema types dominated in cultures. The 16S rRNA gene sequences showed close similarities in the crusts' bacterial composition, with 77-81% of the total clones belonging to cyanobacteria and the rest distributed among Alpha- and Deltaproteobacteria, Bacteriodetes, Gemmatimonas and Planctomycetes. Thirty-seven percent of the cyanobacterial clones were affiliated with heterocystous types such as Nostoc, Scytonema, Brasilonema and Petalonema. Chlorophyll a concentrations suggest a similar abundance of phototrophs in all crusts. High levels of the UVA sunscreen scytonemin were detected in the exposed crusts. The three crusts exhibited comparable acetylene reduction rates in the light and in the dark, with a maximum rate of 58.5+/-2.6 micromol C(2)H(2) reduced m(-2) h( 1). We conclude that the crusts, regardless of their geographical location, were rich in heterocystous cyanobacteria that can fix nitrogen and could possibly improve soil stability and productivity. PMID- 20298502 TI - Nitrifiers and denitrifiers respond rapidly to changed moisture and increasing temperature in a pristine forest soil. AB - Complete cycling of mineral nitrogen (N) in soil requires the interplay of microorganisms performing nitrification and denitrification, whose activity is increasingly affected by extreme rainfall or heat brought about by climate change. In a pristine forest soil, a gradual increase in soil temperature from 5 to 25 degrees C in a range of water contents stimulated N turnover rates, and N gas emissions were determined by the soil water-filled pore space (WFPS). NO and N(2)O emissions dominated at 30% WFPS and 55% WFPS, respectively, and the step wise temperature increase resulted in a threefold increase in the NO(3)(-) concentrations and a decrease in the NH(4)(+) concentration. At 70% WFPS, NH(4)(+) accumulated while NO(3)(-) pools declined, indicating gaseous N loss. AmoA- and nirK-gene-based analysis revealed increasing abundance of bacterial ammonia oxidizers (AOB) with increasing soil temperature and a decrease in the abundance of archaeal ammonia oxidizers (AOA) in wet soil at 25 degrees C, suggesting the sensitivity of the latter to anaerobic conditions. Denitrifier (nirK) community structure was most affected by the water content and nirK gene abundance rapidly increased in response to wet conditions until the substrate (NO(3)(-)) became limiting. Shifts in the community structure were most pronounced for nirK and most rapid for AOA, indicating dynamic populations, whereas distinct adaptation of the AOB communities required 5 weeks, suggesting higher stability. PMID- 20298503 TI - We share the care: family caregivers' experiences of their older relative receiving home support services. AB - Although both family care and home support are considered essential components of home-based health-care, the experiences of family caregivers who have a relative in receipt of home support services are not well understood. Little is known about what aspects of home support services assist family caregivers or hinder them in their caregiving. This study examines family member's experiences of the home support services received by their elderly relatives. Based on a previous Canadian study of contributions in family caregiving, we developed a conceptual model for understanding multiple contributions in caregiving. The present study used this conceptual model to guide the analysis of data from in-depth interviews with family caregivers (N = 52), completed August 2007-April 2008, who have or had an older relative in receipt of home support services in British Columbia, Canada, in the previous 12 months. Verbatim transcripts were read, re-read and independently coded by three members of the research team to identify common themes. Themes relating to direct care (care provided directly to the elderly person) and assistive care (care provided to one caregiver by another) were identified. In discussing the direct care provided by workers, family members emphasised dissatisfaction with instrumental assistance provided by home support workers while also stressing the importance of affective assistance. In commenting about assistive care there were three key themes: caring together, care management, and quality assurance and monitoring. In conclusion, the important role of home support in providing relief for caregivers is highlighted and implications for caregiver policy are discussed. PMID- 20298504 TI - FNR-mediated regulation of bioluminescence and anaerobic respiration in the light organ symbiont Vibrio fischeri. AB - Vibrio fischeri induces both anaerobic respiration and bioluminescence during symbiotic infection. In many bacteria, the oxygen-sensitive regulator FNR activates anaerobic respiration, and a preliminary study using the light generating lux genes from V. fischeri MJ1 cloned in Escherichia coli suggested that FNR stimulates bioluminescence. To test for FNR-mediated regulation of bioluminescence and anaerobic respiration in V. fischeri, we generated fnr mutants of V. fischeri strains MJ1 and ES114. In both strains, FNR was required for normal fumarate- and nitrate-dependent respiration. However, contrary to the report in transgenic E. coli, FNR mediated the repression of lux. ArcA represses bioluminescence, and P(arcA)-lacZ reporters showed reduced expression in fnr mutants, suggesting a possible indirect effect of FNR on bioluminescence via arcA. Finally, the fnr mutant of ES114 was not impaired in colonization of its host squid, Euprymna scolopes. This study extends the characterization of FNR to the Vibrionaceae and underscores the importance of studying lux regulation in its native background. PMID- 20298505 TI - Advanced chronic kidney disease, cardiovascular events and the effect of diabetes: data from the Atherosclerosis and Folic Acid Supplementation Trial. AB - BACKGROUND: End-stage kidney disease registry data have reported increased mortality in patients with diabetes as compared with those without. Here we examine whether diabetes is independently associated with an increased risk of major cardiovascular events and death in patients with advanced chronic kidney disease (CKD). METHODS: Data from 315 participants with CKD in the Atherosclerosis and Folic Acid Supplementation Trial (ASFAST) were assessed. Primary end-points were fatal or non-fatal cardiovascular events, including myocardial infarction, stroke, unstable angina, coronary revascularisation and peripheral vascular events assessed both jointly and separately using Cox proportional hazard models. RESULTS: Twenty-three per cent reported diabetes. Median follow up was 3.6 years. In those with diabetes, an increased risk for major cardiovascular events was observed, crude hazard ratio (HR) 2.87 (95% confidence interval (CI) 2.11-3.90). After adjustment for age, gender, smoking, systolic blood pressure, body mass index, past ischaemic heart disease and use of preventive therapies, diabetes was associated with an HR of 1.83 (1.28-2.61) for major cardiovascular events. The risk for peripheral vascular events was also increased, adjusted HR 6.31 (2.61-15.25). For all-cause death, major coronary and stroke events, the risk in those with diabetes was not significantly increased (all-cause death, adjusted HR 1.31 (95% CI 0.80-2.14); major coronary events, adjusted HR 1.26 (95% CI 0.64-2.49); and major stroke events, adjusted HR 1.28 (95% CI 0.55-2.99)). CONCLUSIONS: Diabetes significantly increases the risk of major cardiovascular events, especially peripheral vascular events in patients with advanced CKD. Trials of multifactorial management of cardiovascular risk factors are required to determine if outcomes for this population may be improved. PMID- 20298506 TI - Assessing individual clinical performance: a primer for physicians. AB - The assessment of individual physician performance has attracted interest from several quarters, including statutory licensing agencies and credentialing bodies of healthcare institutions. Performance measures and assessment methods have been developed, although their validity, reliability and feasibility in regards to physician specialty practice are open to challenge. Despite this, professional colleges and societies will be increasingly obliged to ensure their members are demonstrating high-quality performance on the basis of assessment methods viewed as being transparent, impartial and reproducible. This article provides an overview of the current state of the art which hopefully will serve to inform future debate both within and outside professional circles. PMID- 20298507 TI - Transfer from residential aged care to emergency departments: an analysis of patient outcomes. AB - BACKGROUND: In order to design optimal systems to meet the acute healthcare needs of the frail elderly living in residential care, good clinical information is essential. The aims of this study were to analyse the casemix and outcomes of patients transferred from residential aged care facilities to public hospital emergency departments in New South Wales. METHODS: Individual patient data from six hospital emergency departments and inpatient wards were obtained from merged databases and analysed using descriptive and comparative statistics. RESULTS: Outcomes in 4680 patient transfers over a 12-month period in 2006-2007 were analysed. Transfers occur mostly in high-acuity patients, with approximately three of every four transfers admitted; one in every 12 dying; and admitted patients undergoing an average of 2.4 interventions or procedures during each hospital stay. Several variables are associated with prolonged length of emergency department stay including triage urgency, type of hospital and transfers occurring in winter or out of hours. CONCLUSIONS: Patients transferred from aged care facilities to emergency departments are predominantly high-acuity patients with a substantial likelihood of hospitalisation, intervention and death. Nevertheless, scope exists for some episodes of acute care, in both discharged and admitted patients, to be provided outside a hospital setting. PMID- 20298508 TI - Malignant mesothelioma. AB - Malignant mesothelioma (MM) is an aggressive tumour that commonly affects the mesothelial surfaces of the pleural and peritoneal cavities, and occasionally, the tunica vaginalis and the pericardium. Formerly a rare tumour, MM is increasing in incidence in Australia due to the heavy nationwide use of asbestos from 1940 until the 1980s. The incidence is expected to peak in Australia in the next decade, mirroring the long latency period between asbestos exposure and development of MM. Diagnosis of MM can be difficult. Definitive pathological diagnosis is required and it often requires an experienced pathologist to differentiate MM from other benign or malignant processes. Treatment of MM requires a multidisciplinary approach, regardless of palliative or curative intent. Treatment options, such as surgery, chemotherapy, radiotherapy and active symptom control or a combination of these, may be used. Further research is needed to advance the therapeutic options for MM, and strategies to realize personalisation of therapy through discovery of predictive markers. In the Australian society where asbestos contamination of the built environment is very high, education and stringent public health measures are required to prevent a second wave of increased MM incidence. PMID- 20298509 TI - Craving control using nicotine replacement therapy in a teaching hospital. AB - BACKGROUND: A period of hospitalisation is perhaps the longest period of enforced 'temporary abstinence' smokers have to endure and hence many crave during their admission. Cravings may result in patients' smoking on hospital premises. Nicotine replacement may reduce cravings, decrease smoking on hospital grounds and increase interest in quitting post-discharge. AIM: The aim of this study was to compare the efficacy of two nicotine formulations in controlling inpatient cravings and enthusiasm for quitting post-discharge. METHODS: Inpatients who were smokers were randomised to nicotine patch or inhaler on alternating days. Patients selected their preferred formulation, which was then used for the duration of the hospital stay. Craving control and formulation preference were assessed by visual analogue scales (VAS), and interest in quitting on a 3-point scale. Abstinence was confirmed by exhaled breath CO monitoring. RESULTS: Patches were preferred by 64% of the 367 subjects. Fewer patients went outside to smoke after either formulation (37% before, 5% after enrolment). Cravings were reduced by both nicotine formulations (mean VAS score fell from 7.5 to 1.7). Interest in quitting post-discharge increased. Estimated mean exposure to nicotine was 5 mg/day (inhaler), 15 mg/day (transdermal patch) compared with 30 mg/day (cigarettes) before hospitalisation. CONCLUSIONS: Many smokers crave and some smoke outside during a hospital admission. While the patch was the preferred formulation of nicotine replacement therapy, both were effective in reducing cravings, increasing motivation for quitting post-discharge and improving Hospital 'image' by reducing smoking on campus. Nicotine replacement therapy should be made available to inpatients in all hospitals and other places of enforced prolonged abstinence. PMID- 20298510 TI - Smoking prevalence and perspectives on smoking on campus by employees in Australian teaching hospitals. AB - BACKGROUND: Cigarette smoking prevalence has been declining over decades in Western countries especially in higher socioeconomic groups. Employees of Australian hospitals span the socioeconomic spectrum, but there are few data on smoking prevalence from these workplaces. Because smoking is a health hazard, some argue that it should be banned on hospital premises, but employees' opinions appear not to have been widely canvassed. Cigarette smoking is a particular problem in hospitals because of the need for prolonged abstinence by immobile patients and the stressors that accompany life-and-death events for patients and/or relatives. The Queen Elizabeth Hospital has had a Stop Smoking Service for >10 years, but how smoking prevalence has changed and how it compares with similar hospitals is unknown. AIMS: The aims of this study were (i) to determine smoking prevalence by employees of The Queen Elizabeth Hospital and to compare this with employees of other hospitals and (ii) to ascertain employees' perspectives regarding smoking on hospital grounds. METHODS: Single page questionnaires were forwarded to employees of four South Australian/Northern Territory hospitals enquiring about smoking status, employment category, views about smoking on hospital premises, etc. Responses were voluntary. RESULTS: Response rates were 39-59%. Smoking prevalence has steadily declined at The Queen Elizabeth Hospital and is now 8.4%. Prevalence at comparator hospitals was approximately double this value. Most staff thought the visibility of smoking was problematic, but support for providing smoking area/s was greater than for a hospital-wide ban. CONCLUSIONS: The ongoing decline in smoking prevalence at The Queen Elizabeth Hospital is probably the result of the Staff Stop Smoking Service. PMID- 20298511 TI - Descriptive analysis of emergency department oxygen use in acute exacerbation of chronic obstructive pulmonary disease. AB - BACKGROUND: Inconsistencies in oxygen therapy recommendations in acute exacerbation of chronic obstructive pulmonary disease (COPD) may result in variability in emergency department (ED) oxygen management of patients with COPD. The aim of this study was to describe oxygen management in the first 4 h of ED care for patients with exacerbation of COPD. METHODS: A retrospective medical record audit was conducted at four public and one private ED in Melbourne, Australia. Participants were 273 adult ED patients with COPD presenting with a primary complaint of shortness of breath from July 2006 to July 2007. Outcome measures were physiological data, including oxygen saturation (SpO(2)), oxygen delivery devices and flow rates on ED arrival, 1 and 4 h. RESULTS: Oxygen was used in 82.0% of patients. Patients who required oxygen had higher incidence of ambulance transport (P < 0.001), triage category 2 (P = 0.006), home oxygen use (P < 0.001), and increased work of breathing on ED arrival (P < 0.001), and higher median respiratory rate (P < 0.001) and heart rate (P = 0.001). SpO(2) > 90% occurred in the majority of patients (87.5%; 96.4%; 95.6%); however, a considerable number of patients with SpO(2) < 90% were not given oxygen (61.8%; 30%; 45.5%). CONCLUSIONS: A number of patients with documented hypoxaemia were not given oxygen and there may be variables other than oxygen saturation that may influence oxygen use. Future research should focus on increasing the evidence based supporting oxygen use and better understanding of clinicians' oxygen decision-making in patients with COPD. PMID- 20298512 TI - Severe hyponatraemia in elderly hospitalized patients: prevalence, aetiology and outcome. AB - BACKGROUND: Hyponatraemia is the commonest electrolyte disorder in the elderly. Data on severe hyponatraemia and the prevalence of cerebral salt wasting syndrome (CSWS) in elderly hospitalized patients are lacking. We studied the incidence, frequency of various aetiologies, outcome and the possible role of CSWS in severe hyponatraemia in elderly medical patients. METHODS: A prospective, observational, non-interventional study conducted over a 5-month period in medical wards. Eighty six patients aged over 65 years with serum sodium levels < or =125 mEq/L were included. All patients were examined by one of the authors, who also evaluated potential contributing factors. Demographic, clinical and outcome data were extracted from the medical records. RESULTS: The mean age of the patients was 82.1 + 8.7 years. The prevalence of hyponatraemia was 6.2% (8.1% women and 4.0% men (P < 0.001)). There was no increase in incidence of hyponatraemia with age. The leading cause of hyponatraemia was the syndrome of inappropriate antidiuretic hormone secretion (SIADH), whose aetiology could be determined in only 46% of cases. Aetiology was multifactorial in 51% of patients (1.7 aetiological factors per patient). All patients with thiazide-induced hyponatraemia had other contributing factors. Hyperglycaemia and hypoalbuminaemia were predictors of neurological manifestations of hyponatraemia. Overall in-hospital mortality was 19%. Only hypoalbuminaemia was found as an independent risk factor for death. In none of the patients was the hyponatraemia due to CSWS. CONCLUSION: Severe hyponatraemia in elderly hospitalized medical patients is more frequent in women and of multifactorial aetiology in 50% of cases. It is most commonly caused by SIADH; CSWS is an unlikely cause. PMID- 20298513 TI - Panallergens and their impact on the allergic patient. AB - The panallergen concept encompasses families of related proteins, which are involved in general vital processes and thus, widely distributed throughout nature. Plant panallergens share highly conserved sequence regions, structure, and function. They are responsible for many IgE cross-reactions even between unrelated pollen and plant food allergen sources. Although usually considered as minor allergens, sensitization to panallergens might be problematic as it bears the risk of developing multiple sensitizations. Clinical manifestations seem to be tightly connected with geographical and exposure factors. Future population- and disease-based screenings should provide new insights on panallergens and their contribution to disease manifestations. Such information requires molecule based diagnostics and will be valuable for developing patient-tailored prophylactic and therapeutic approaches. In this article, we focus on profilins, non-specific lipid transfer proteins, polcalcins, and Bet v 1-related proteins and discuss possible consequences of panallergen sensitization for the allergic patient. Based on their pattern of IgE cross-reactivity, which is reflected by their distribution in the plant kingdom, we propose a novel classification of panallergens into ubiquitously spread "real panallergens" (e.g. profilins) and widespread "eurallergens" (e.g. polcalcins). "Stenallergens" display more limited distribution and cross-reactivity patterns, and "monallergens" are restricted to a single allergen source. PMID- 20298514 TI - Skin prick testing in patients using beta-blockers: a retrospective analysis. AB - RATIONALE: The use of beta-blockers is a relative contraindication in allergen skin testing yet there is a paucity of literature on adverse events in this circumstance. We examined a population of skin tested patients on beta-blockers to look for any adverse effects. METHODS: Charts from 2004-2008 in a single allergy clinic were reviewed for any patients taking a beta-blocker when skin tested. Data was examined for skin test reactivity, type of skin test, concomitant asthma diagnosis, allergens tested, and adverse events. RESULTS: One hundred and ninety-one patients were taking beta-blockers when skin testing occurred. Seventy-two patients had positive skin tests. No tests resulted in an adverse event. CONCLUSIONS: This data demonstrates the relative safety of administrating of skin prick tests to patients on beta-blocker treatment. Larger prospective studies are needed to substantiate the findings of this study. PMID- 20298515 TI - Alterations in the complement cascade in post-traumatic stress disorder. AB - BACKGROUND: In the present study we assessed the functional state of the major mediator of the immune response, the complement system, in post-traumatic stress disorder (PTSD). METHODS: Thirty one PTSD patients within 13 years from traumatic event and the same number of sex- and age-matched healthy volunteers were involved in this study. In the blood serum of the study subjects hemolytic activities of the classical and alternative complement pathways, as well as the activities of the individual complement components have been measured. Correlation analysis between all measured parameters was also performed. RESULTS: According to the results obtained PTSD is characterized by hyperactivation of the complement classical pathway, hypoactivation of the complement alternative pathway and overactivation of the terminal pathway. CONCLUSIONS: The results obtained provide further evidence on the involvement of the inflammatory component in pathogenesis of PTSD. PMID- 20298516 TI - Quantitative assessment of the expanding complementarity between public and commercial databases of bioactive compounds. AB - BACKGROUND: Since 2004 public cheminformatic databases and their collective functionality for exploring relationships between compounds, protein sequences, literature and assay data have advanced dramatically. In parallel, commercial sources that extract and curate such relationships from journals and patents have also been expanding. This work updates a previous comparative study of databases chosen because of their bioactive content, availability of downloads and facility to select informative subsets. RESULTS: Where they could be calculated, extracted compounds-per-journal article were in the range of 12 to 19 but compound-per protein counts increased with document numbers. Chemical structure filtration to facilitate standardised comparisons typically reduced source counts by between 5% and 30%. The pair-wise overlaps between 23 databases and subsets were determined, as well as changes between 2006 and 2008. While all compound sets have increased, PubChem has doubled to 14.2 million. The 2008 comparison matrix shows not only overlap but also unique content across all sources. Many of the detailed differences could be attributed to individual strategies for data selection and extraction. While there was a big increase in patent-derived structures entering PubChem since 2006, GVKBIO contains over 0.8 million unique structures from this source. Venn diagrams showed extensive overlap between compounds extracted by independent expert curation from journals by GVKBIO, WOMBAT (both commercial) and BindingDB (public) but each included unique content. In contrast, the approved drug collections from GVKBIO, MDDR (commercial) and DrugBank (public) showed surprisingly low overlap. Aggregating all commercial sources established that while 1 million compounds overlapped with PubChem 1.2 million did not. CONCLUSION: On the basis of chemical structure content per se public sources have covered an increasing proportion of commercial databases over the last two years. However, commercial products included in this study provide links between compounds and information from patents and journals at a larger scale than current public efforts. They also continue to capture a significant proportion of unique content. Our results thus demonstrate not only an encouraging overall expansion of data-supported bioactive chemical space but also that both commercial and public sources are complementary for its exploration. PMID- 20298517 TI - DPRESS: Localizing estimates of predictive uncertainty. AB - BACKGROUND: The need to have a quantitative estimate of the uncertainty of prediction for QSAR models is steadily increasing, in part because such predictions are being widely distributed as tabulated values disconnected from the models used to generate them. Classical statistical theory assumes that the error in the population being modeled is independent and identically distributed (IID), but this is often not actually the case. Such inhomogeneous error (heteroskedasticity) can be addressed by providing an individualized estimate of predictive uncertainty for each particular new object u: the standard error of prediction su can be estimated as the non-cross-validated error st* for the closest object t* in the training set adjusted for its separation d from u in the descriptor space relative to the size of the training set.The predictive uncertainty factor gammat* is obtained by distributing the internal predictive error sum of squares across objects in the training set based on the distances between them, hence the acronym: Distributed PRedictive Error Sum of Squares (DPRESS). Note that st* and gammat*are characteristic of each training set compound contributing to the model of interest. RESULTS: The method was applied to partial least-squares models built using 2D (molecular hologram) or 3D (molecular field) descriptors applied to mid-sized training sets (N = 75) drawn from a large (N = 304), well-characterized pool of cyclooxygenase inhibitors. The observed variation in predictive error for the external 229 compound test sets was compared with the uncertainty estimates from DPRESS. Good qualitative and quantitative agreement was seen between the distributions of predictive error observed and those predicted using DPRESS. Inclusion of the distance-dependent term was essential to getting good agreement between the estimated uncertainties and the observed distributions of predictive error. The uncertainty estimates derived by DPRESS were conservative even when the training set was biased, but not excessively so. CONCLUSION: DPRESS is a straightforward and powerful way to reliably estimate individual predictive uncertainties for compounds outside the training set based on their distance to the training set and the internal predictive uncertainty associated with its nearest neighbor in that set. It represents a sample-based, a posteriori approach to defining applicability domains in terms of localized uncertainty. PMID- 20298518 TI - Small Molecule Subgraph Detector (SMSD) toolkit. AB - BACKGROUND: Finding one small molecule (query) in a large target library is a challenging task in computational chemistry. Although several heuristic approaches are available using fragment-based chemical similarity searches, they fail to identify exact atom-bond equivalence between the query and target molecules and thus cannot be applied to complex chemical similarity searches, such as searching a complete or partial metabolic pathway.In this paper we present a new Maximum Common Subgraph (MCS) tool: SMSD (Small Molecule Subgraph Detector) to overcome the issues with current heuristic approaches to small molecule similarity searches. The MCS search implemented in SMSD incorporates chemical knowledge (atom type match with bond sensitive and insensitive information) while searching molecular similarity. We also propose a novel method by which solutions obtained by each MCS run can be ranked using chemical filters such as stereochemistry, bond energy, etc. RESULTS: In order to benchmark and test the tool, we performed a 50,000 pair-wise comparison between KEGG ligands and PDB HET Group atoms. In both cases the SMSD was shown to be more efficient than the widely used MCS module implemented in the Chemistry Development Kit (CDK) in generating MCS solutions from our test cases. CONCLUSION: Presently this tool can be applied to various areas of bioinformatics and chemo-informatics for finding exhaustive MCS matches. For example, it can be used to analyse metabolic networks by mapping the atoms between reactants and products involved in reactions. It can also be used to detect the MCS/substructure searches in small molecules reported by metabolome experiments, as well as in the screening of drug like compounds with similar substructures.Thus, we present a robust tool that can be used for multiple applications, including the discovery of new drug molecules. This tool is freely available on http://www.ebi.ac.uk/thornton-srv/software/SMSD/ PMID- 20298519 TI - Fast automated placement of polar hydrogen atoms in protein-ligand complexes. AB - BACKGROUND: Hydrogen bonds play a major role in the stabilization of protein ligand complexes. The ability of a functional group to form them depends on the position of its hydrogen atoms. An accurate knowledge of the positions of hydrogen atoms in proteins is therefore important to correctly identify hydrogen bonds and their properties. The high mobility of hydrogen atoms introduces several degrees of freedom: Tautomeric states, where a hydrogen atom alters its binding partner, torsional changes where the position of the hydrogen atom is rotated around the last heavy-atom bond in a residue, and protonation states, where the number of hydrogen atoms at a functional group may change. Also, side chain flips in glutamine and asparagine and histidine residues, which are common crystallographic ambiguities must be identified before structure-based calculations can be conducted. RESULTS: We have implemented a method to determine the most probable hydrogen atom positions in a given protein-ligand complex. Optimality of hydrogen bond geometries is determined by an empirical scoring function which is used in molecular docking. This allows to evaluate protein ligand interactions with an established model. Also, our method allows to resolve common crystallographic ambiguities such as as flipped amide groups and histidine residues. To ensure high speed, we make use of a dynamic programming approach. CONCLUSION: Our results were checked against selected high-resolution structures from an external dataset, for which the positions of the hydrogen atoms have been validated manually. The quality of our results is comparable to that of other programs, with the advantage of being fast enough to be applied on-the-fly for interactive usage or during score evaluation. PMID- 20298520 TI - Shape: automatic conformation prediction of carbohydrates using a genetic algorithm. AB - BACKGROUND: Detailed experimental three dimensional structures of carbohydrates are often difficult to acquire. Molecular modelling and computational conformation prediction are therefore commonly used tools for three dimensional structure studies. Modelling procedures generally require significant training and computing resources, which is often impractical for most experimental chemists and biologists. Shape has been developed to improve the availability of modelling in this field. RESULTS: The Shape software package has been developed for simplicity of use and conformation prediction performance. A trivial user interface coupled to an efficient genetic algorithm conformation search makes it a powerful tool for automated modelling. Carbohydrates up to a few hundred atoms in size can be investigated on common computer hardware. It has been shown to perform well for the prediction of over four hundred bioactive oligosaccharides, as well as compare favourably with previously published studies on carbohydrate conformation prediction. CONCLUSION: The Shape fully automated conformation prediction can be used by scientists who lack significant modelling training, and performs well on computing hardware such as laptops and desktops. It can also be deployed on computer clusters for increased capacity. The prediction accuracy under the default settings is good, as it agrees well with experimental data and previously published conformation prediction studies. This software is available both as open source and under commercial licenses. PMID- 20298521 TI - OrChem - An open source chemistry search engine for Oracle(R). AB - BACKGROUND: Registration, indexing and searching of chemical structures in relational databases is one of the core areas of cheminformatics. However, little detail has been published on the inner workings of search engines and their development has been mostly closed-source. We decided to develop an open source chemistry extension for Oracle, the de facto database platform in the commercial world. RESULTS: Here we present OrChem, an extension for the Oracle 11G database that adds registration and indexing of chemical structures to support fast substructure and similarity searching. The cheminformatics functionality is provided by the Chemistry Development Kit. OrChem provides similarity searching with response times in the order of seconds for databases with millions of compounds, depending on a given similarity cut-off. For substructure searching, it can make use of multiple processor cores on today's powerful database servers to provide fast response times in equally large data sets. AVAILABILITY: OrChem is free software and can be redistributed and/or modified under the terms of the GNU Lesser General Public License as published by the Free Software Foundation. All software is available via http://orchem.sourceforge.net. PMID- 20298522 TI - The PubChem chemical structure sketcher. AB - PubChem is an important public, Web-based information source for chemical and bioactivity information. In order to provide convenient structure search methods on compounds stored in this database, one mandatory component is a Web-based drawing tool for interactive sketching of chemical query structures. Web-enabled chemical structure sketchers are not new, being in existence for years; however, solutions available rely on complex technology like Java applets or platform dependent plug-ins. Due to general policy and support incident rate considerations, Java-based or platform-specific sketchers cannot be deployed as a part of public NCBI Web services. Our solution: a chemical structure sketching tool based exclusively on CGI server processing, client-side JavaScript functions, and image sequence streaming. The PubChem structure editor does not require the presence of any specific runtime support libraries or browser configurations on the client. It is completely platform-independent and verified to work on all major Web browsers, including older ones without support for Web2.0 JavaScript objects. PMID- 20298523 TI - Evaluation of a Bayesian inference network for ligand-based virtual screening. AB - BACKGROUND: Bayesian inference networks enable the computation of the probability that an event will occur. They have been used previously to rank textual documents in order of decreasing relevance to a user-defined query. Here, we modify the approach to enable a Bayesian inference network to be used for chemical similarity searching, where a database is ranked in order of decreasing probability of bioactivity. RESULTS: Bayesian inference networks were implemented using two different types of network and four different types of belief function. Experiments with the MDDR and WOMBAT databases show that a Bayesian inference network can be used to provide effective ligand-based screening, especially when the active molecules being sought have a high degree of structural homogeneity; in such cases, the network substantially out-performs a conventional, Tanimoto based similarity searching system. However, the effectiveness of the network is much less when structurally heterogeneous sets of actives are being sought. CONCLUSION: A Bayesian inference network provides an interesting alternative to existing tools for ligand-based virtual screening. PMID- 20298524 TI - Combining docking with pharmacophore filtering for improved virtual screening. AB - BACKGROUND: Virtual screening is used to distinguish potential leads from inactive compounds in a database of chemical samples. One method for accomplishing this is by docking compounds into the structure of a receptor binding site in order to rank-order compounds by the quality of the interactions they form with the receptor. It is generally established that docking can be reasonably successful at generating good poses of a ligand in an active site. However, the scoring functions that are used with docking are typically not successful at correctly ranking ligands according to binding affinity or even distinguishing correct poses of a given ligand from incorrect ones. RESULTS: We have developed a simple method for reducing the number of false positives in a virtual screen, meaning ligands which are scored highly by the docking program but do not bind well in reality. This method uses a docking program for pose generation without regard to scoring, followed by filtering with receptor-based pharmacophore searches. We applied it to three test-case targets: neuraminidase A, cyclin-dependent kinase 2, and the C1 domain of protein kinase C. CONCLUSION: The pharmacophore filtering method can perform better than more traditional docking + scoring methods, and allows the advantages of both docking-based and pharmacophore-based approaches to virtual screening to be fully realized. PMID- 20298525 TI - Large scale study of multiple-molecule queries. AB - BACKGROUND: In ligand-based screening, as well as in other chemoinformatics applications, one seeks to effectively search large repositories of molecules in order to retrieve molecules that are similar typically to a single molecule lead. However, in some case, multiple molecules from the same family are available to seed the query and search for other members of the same family.Multiple-molecule query methods have been less studied than single-molecule query methods. Furthermore, the previous studies have relied on proprietary data and sometimes have not used proper cross-validation methods to assess the results. In contrast, here we develop and compare multiple-molecule query methods using several large publicly available data sets and background. We also create a framework based on a strict cross-validation protocol to allow unbiased benchmarking for direct comparison in future studies across several performance metrics. RESULTS: Fourteen different multiple-molecule query methods were defined and benchmarked using: (1) 41 publicly available data sets of related molecules with similar biological activity; and (2) publicly available background data sets consisting of up to 175,000 molecules randomly extracted from the ChemDB database and other sources. Eight of the fourteen methods were parameter free, and six of them fit one or two free parameters to the data using a careful cross-validation protocol. All the methods were assessed and compared for their ability to retrieve members of the same family against the background data set by using several performance metrics including the Area Under the Accumulation Curve (AUAC), Area Under the Curve (AUC), F1-measure, and BEDROC metrics.Consistent with the previous literature, the best parameter-free methods are the MAX-SIM and MIN-RANK methods, which score a molecule to a family by the maximum similarity, or minimum ranking, obtained across the family. One new parameterized method introduced in this study and two previously defined methods, the Exponential Tanimoto Discriminant (ETD), the Tanimoto Power Discriminant (TPD), and the Binary Kernel Discriminant (BKD), outperform most other methods but are more complex, requiring one or two parameters to be fit to the data. CONCLUSION: Fourteen methods for multiple molecule querying of chemical databases, including novel methods, (ETD) and (TPD), are validated using publicly available data sets, standard cross validation protocols, and established metrics. The best results are obtained with ETD, TPD, BKD, MAX-SIM, and MIN-RANK. These results can be replicated and compared with the results of future studies using data freely downloadable from http://cdb.ics.uci.edu/. PMID- 20298526 TI - Estimation of synthetic accessibility score of drug-like molecules based on molecular complexity and fragment contributions. AB - BACKGROUND: A method to estimate ease of synthesis (synthetic accessibility) of drug-like molecules is needed in many areas of the drug discovery process. The development and validation of such a method that is able to characterize molecule synthetic accessibility as a score between 1 (easy to make) and 10 (very difficult to make) is described in this article. RESULTS: The method for estimation of the synthetic accessibility score (SAscore) described here is based on a combination of fragment contributions and a complexity penalty. Fragment contributions have been calculated based on the analysis of one million representative molecules from PubChem and therefore one can say that they capture historical synthetic knowledge stored in this database. The molecular complexity score takes into account the presence of non-standard structural features, such as large rings, non-standard ring fusions, stereocomplexity and molecule size. The method has been validated by comparing calculated SAscores with ease of synthesis as estimated by experienced medicinal chemists for a set of 40 molecules. The agreement between calculated and manually estimated synthetic accessibility is very good with r2 = 0.89. CONCLUSION: A novel method to estimate synthetic accessibility of molecules has been developed. This method uses historical synthetic knowledge obtained by analyzing information from millions of already synthesized chemicals and considers also molecule complexity. The method is sufficiently fast and provides results consistent with estimation of ease of synthesis by experienced medicinal chemists. The calculated SAscore may be used to support various drug discovery processes where a large number of molecules needs to be ranked based on their synthetic accessibility, for example when purchasing samples for screening, selecting hits from high-throughput screening for follow-up, or ranking molecules generated by various de novo design approaches. PMID- 20298527 TI - The Spectral Game: leveraging Open Data and crowdsourcing for education. AB - We report on the implementation of the Spectral Game, a web-based game where players try to match molecules to various forms of interactive spectra including 1D/2D NMR, Mass Spectrometry and Infrared spectra. Each correct selection earns the player one point and play continues until the player supplies an incorrect answer. The game is usually played using a web browser interface, although a version has been developed in the virtual 3D environment of Second Life. Spectra uploaded as Open Data to ChemSpider in JCAMP-DX format are used for the problem sets together with structures extracted from the website. The spectra are displayed using JSpecView, an Open Source spectrum viewing applet which affords zooming and integration. The application of the game to the teaching of proton NMR spectroscopy in an undergraduate organic chemistry class and a 2D Spectrum Viewer are also presented. PMID- 20298528 TI - Molecular structure input on the web. AB - A molecule editor, that is program for input and editing of molecules, is an indispensable part of every cheminformatics or molecular processing system. This review focuses on a special type of molecule editors, namely those that are used for molecule structure input on the web. Scientific computing is now moving more and more in the direction of web services and cloud computing, with servers scattered all around the Internet. Thus a web browser has become the universal scientific user interface, and a tool to edit molecules directly within the web browser is essential.The review covers a history of web-based structure input, starting with simple text entry boxes and early molecule editors based on clickable maps, before moving to the current situation dominated by Java applets. One typical example - the popular JME Molecule Editor - will be described in more detail. Modern Ajax server-side molecule editors are also presented. And finally, the possible future direction of web-based molecule editing, based on technologies like JavaScript and Flash, is discussed. PMID- 20298529 TI - Notch regulates the angiogenic response via induction of VEGFR-1. AB - Notch is a critical regulator of angiogenesis and arterial specification. We show that ectopic expression of activated Notch1 induces endothelial morphogenesis in human umbilical vein endothelial cells (HUVEC) in a VEGFR-1-dependent manner. Notch1-mediated upregulation of VEGFR-1 in HUVEC increased their responsiveness to the VEGFR-1 specific ligand, Placental Growth Factor (PlGF). In mice and human endothelial cells, inhibition of Notch signaling resulted in decreased VEGFR-1 expression during VEGF-A-induced neovascularization. In summary, we show that Notch1 plays a role in endothelial cells by regulating VEGFR-1, a function that may be important for physiological and pathological angiogenesis. PMID- 20298530 TI - A role for Egfl7 during endothelial organization in the embryoid body model system. AB - Epidermal growth factor-like domain 7, Egfl7, is a largely endothelial restricted gene which is thought to have a role during the differentiation of embryonic stem cells (ESCs) along the endothelial lineage. While it has been shown that Egfl7 knock-down in zebrafish impairs endothelial cord formation, the role of the gene in mammals has been unresolved. Interpretation of mouse knockout studies has been complicated by the fact that deletion of miR-126, an intronic microRNA located within Egfl7, results in vascular defects. Here we use an siRNA knock-down approach to target specific regions of Egfl7 without affecting miR-126 expression. Egfl7 was knocked down in mouse ESCs and the effect on vascular development was assessed using the in vitro embryoid body (EB) model after either 7 or 14 days of differentiation. Knock-down of Egfl7 resulted in the formation of abnormal sheet-like CD31+ structures that were abundant within EBs after 7 days of differentiation. Only up to 60% of these sheets co-expressed basement membrane and endothelial cell junction markers. Similar CD31+ sheets were also seen as outgrowths from 7 day EBs into collagen gels. A partial remodelling occurred by 14 days of differentiation when fewer CD31+ sheets were seen both within EBs, and as outgrowths from EBs. Formation of these sheets was due, at least in part, to increased proliferation specifically of CD31+ cells. Cell death within EBs was unaffected by Egfl7 knock-down. In conclusion, our work shows that knock-down of Egfl7 causes defects in early vascular cord formation, and results in the development of CD31+ sheet-like structures. This suggests that Egfl7 is vital for the formation of endothelial cell cords, and that the gene has an important role during both vasculogenesis and angiogenesis in mammalian cells. PMID- 20298531 TI - Methylnaltrexone potentiates the anti-angiogenic effects of mTOR inhibitors. AB - BACKGROUND: Recent cancer therapies include drugs that target both tumor growth and angiogenesis including mammalian target of rapamycin (mTOR) inhibitors. Since mTOR inhibitor therapy is associated with significant side effects, we examined potential agents that can reduce the therapeutic dose. METHODS: Methylnaltrexone (MNTX), a peripheral mu opioid receptor (MOR) antagonist, in combination with the mTOR inhibitors temsirolimus and/or rapamycin, was evaluated for inhibition of VEGF-induced human pulmonary microvascular endothelial cell (EC) proliferation and migration as well as in vivo angiogenesis (mouse Matrigel plug assay). RESULTS: MNTX inhibited VEGF-induced EC proliferation and migration with an IC50 of approximately 100 nM. Adding 10 nM MNTX to EC shifted the IC50 of temsirolimus inhibition of VEGF-induced proliferation and migration from approximately 10 nM to approximately 1 nM and from approximately 50 to approximately 10 nM respectively. We observed similar effects with rapamycin. On a mechanistic level, we observed that MNTX increased EC plasma membrane-associated tyrosine phosphate activity. Inhibition of tyrosine phosphatase activity (3,4-dephostatin) blocked the synergy between MNTX and temsirolimus and increased VEGF-induced tyrosine phosphorylation of Src with enhanced PI3 kinase and mTOR Complex 2-dependent phosphorylation of Akt and subsequent activation of mTOR Complex 1 (rapamycin and temsirolimus target), while silencing Src, Akt or mTOR complex 2 components blocked VEGF-induced angiogenic events. CONCLUSIONS: Our data indicate that MNTX exerts a synergistic effect with rapamycin and temsirolimus on inhibition of VEGF induced human EC proliferation and migration and in vivo angiogenesis. Therefore, addition of MNTX could potentially lower the dose of mTOR inhibitors which could improve therapeutic index. PMID- 20298532 TI - Endothelial progenitor cells: what use for the cardiologist? AB - Endothelial Progenitor Cells (EPC) were first described in 1997 and have since been the subject of numerous investigative studies exploring the potential of these cells in the process of cardiovascular damage and repair. Whilst their exact definition and mechanism of action remains unclear, they are directly influenced by different cardiovascular risk factors and have a definite role to play in defining cardiovascular risk. Furthermore, EPCs may have important therapeutic implications and further understanding of their pathophysiology has enabled us to explore new possibilities in the management of cardiovascular disease. This review article aims to provide an overview of the vast literature on EPCs in relation to clinical cardiology. PMID- 20298533 TI - Micro computed tomography for vascular exploration. AB - Vascular exploration of small animals requires imaging hardware with a very high spatial resolution, capable of differentiating large as well as small vessels, in both in vivo and ex vivo studies. Micro Computed Tomography (micro-CT) has emerged in recent years as the preferred modality for this purpose, providing high resolution 3D volumetric data suitable for analysis, quantification, validation, and visualization of results. The usefulness of micro-CT, however, can be adversely affected by a range of factors including physical animal preparation, numerical quantification, visualization of results, and quantification software with limited possibilities. Exacerbating these inherent difficulties is the lack of a unified standard for micro-CT imaging. Most micro CT today is aimed at particular applications and the software tools needed for quantification, developed mainly by imaging hardware manufacturers, lack the level of detail needed to address more specific aims. This review highlights the capabilities of micro-CT for vascular exploration, describes the current state of imaging protocols, and offers guidelines and suggestions aimed at making micro-CT more accurate, replicable, and robust. PMID- 20298535 TI - Intracarotid administration of human bone marrow mononuclear cells in rat photothrombotic ischemia. AB - BACKGROUND: Increasing evidence suggests that cell therapy improves functional recovery in experimental models of stroke and myocardial infarction. So far only small pilot trials tested the effects of cell therapy in stroke patients, whereas large clinical trials were conducted in patients with ischemic heart disease. To investigate the therapeutic benefit of cell therapy to improve the recovery after stroke, we determined the efficacy of bone marrow derived mononuclear cells, which were shown to improve the recovery in experimental and clinical acute myocardial infarction studies, in a rat stroke model. METHODS: Adult male Wistar rats were randomly assigned to receive either five million human bone marrow mononuclear cells (hBMC) or placebo intraarterially 3 days after photothrombotic ischemia. For immunosuppression the animals received daily injections of cyclosporine throughout the experiment, commencing 24 hours before the cell transplantation. A battery of behavioral tests was performed before and up to 4 weeks after ischemia. RESULTS: Body temperature and body weight revealed no difference between groups. Neurological deficits measured by the Rotarod test, the adhesive-removal test and the cylinder test were not improved by hBMC transplantation compared to placebo. CONCLUSIONS: This study demonstrates that hBMC do not improve functional recovery when transplanted intraaterially 3 days after the onset of focal cerebral ischemia. A possible reason for the failed neurological improvement after cell therapy might be the delayed treatment initiation compared to other experimental stroke studies that showed efficacy of bone marrow mononuclear cells. PMID- 20298536 TI - In vivo MRI assessment of permanent middle cerebral artery occlusion by electrocoagulation: pitfalls of procedure. AB - Permanent middle cerebral artery (MCA) occlusion (pMCAO) by electrocoagulation is a commonly used model but with potential traumatic lesions. Early MRI monitoring may assess pMCAO for non-specific brain damage. The surgical steps of pMCAO were evaluated for traumatic cerebral injury in 22 Swiss mice using diffusion and T2 weighted MRI (7T) performed within 1 h and 24 h after surgery. Temporal muscle cauterization without MCA occlusion produced an early T2 hyperintensity mimicking an infarct. No lesion was visible after temporal muscle incision or craniotomy. Early MRI monitoring is useful to identify non-specific brain injury that could hamper neuroprotective drugs assessment. PMID- 20298534 TI - Preconditioning-induced ischemic tolerance: a window into endogenous gearing for cerebroprotection. AB - Ischemic tolerance defines transient resistance to lethal ischemia gained by a prior sublethal noxious stimulus (i.e., preconditioning). This adaptive response is thought to be an evolutionarily conserved defense mechanism, observed in a wide variety of species. Preconditioning confers ischemic tolerance if not in all, in most organ systems, including the heart, kidney, liver, and small intestine. Since the first landmark experimental demonstration of ischemic tolerance in the gerbil brain in early 1990's, basic scientific knowledge on the mechanisms of cerebral ischemic tolerance increased substantially. Various noxious stimuli can precondition the brain, presumably through a common mechanism, genomic reprogramming. Ischemic tolerance occurs in two temporally distinct windows. Early tolerance can be achieved within minutes, but wanes also rapidly, within hours. Delayed tolerance develops in hours and lasts for days. The main mechanism involved in early tolerance is adaptation of membrane receptors, whereas gene activation with subsequent de novo protein synthesis dominates delayed tolerance. Ischemic preconditioning is associated with robust cerebroprotection in animals. In humans, transient ischemic attacks may be the clinical correlate of preconditioning leading to ischemic tolerance. Mimicking the mechanisms of this unique endogenous protection process is therefore a potential strategy for stroke prevention. Perhaps new remedies for stroke are very close, right in our cells. PMID- 20298537 TI - COU254, a specific 3-carboxamide-coumarin inhibitor of coagulation factor XII, does not protect mice from acute ischemic stroke. AB - BACKGROUND: Anticoagulation is an important means to prevent from acute ischemic stroke but is associated with a significant risk of severe hemorrhages. Previous studies have shown that blood coagulation factor XII (FXII)-deficient mice are protected from pathological thrombus formation during cerebral ischemia without bearing an increased bleeding tendency. Hence, pharmacological blockade of FXII might be a promising and safe approach to prevent acute ischemic stroke and possibly other thromboembolic disorders but pharmacological inhibitors selective over FXII are still lacking. In the present study we investigated the efficacy of COU254, a novel nonpeptidic 3-carboxamide-coumarin that selectively blocks FXII activity, on stroke development and post stroke functional outcome in mice. METHODS: C57Bl/6 mice were treated with COU254 (40 mg/kg i.p.) or vehicle and subjected to 60 min transient middle cerebral artery occlusion (tMCAO) using the intraluminal filament method. After 24 h infarct volumes were determined from 2,3,5-Triphenyltetrazoliumchloride(TTC)-stained brain sections and functional scores were assessed. Hematoxylin and eosin (H&E) staining was used to estimate the extent of neuronal cell damage. Thrombus formation within the infarcted brain areas was analyzed by immunoblot. RESULTS: Infarct volumes and functional outcomes on day 1 after tMCAO did not significantly differ between COU254 pre treated mice or untreated controls (p > 0.05). Histology revealed extensive ischemic neuronal damage regularly including the cortex and the basal ganglia in both groups. COU254 treatment did not prevent intracerebral fibrin(ogen) formation. CONCLUSIONS: COU254 at the given concentration of 40 mg/kg failed to demonstrate efficacy in acute ischemic stroke in this preliminary study. Further preclinical evaluation of 3-carboxamide-coumarins is needed before the antithrombotic potential of this novel class of FXII inhibitors can be finally judged. PMID- 20298538 TI - Patient safety in surgery: non-technical aspects of safe surgical performance. AB - The performance of operative surgery has an understandable focus placed on dexterity, technical precision, as well as the choice of procedure. There is less appreciation of the cognitive and social skills of the individual surgeon and the effect that these have on the surgical team and on patient outcome. This article highlights that impact and explores the contribution of non-technical skills to safe practice within the operating room. PMID- 20298540 TI - British pain clinic practitioners' recognition and use of the bio-psychosocial pain management model for patients when physical interventions are ineffective or inappropriate: results of a qualitative study. AB - BACKGROUND: To explore how chronic musculoskeletal pain is managed in multidisciplinary pain clinics for patients for whom physical interventions are inappropriate or ineffective. METHODS: A qualitative study was undertaken using semi-structured interviews with twenty five members of the pain management team drawn from seven pain clinics and one pain management unit located across the UK. RESULTS: All clinics reported using a multidisciplinary bio-psychosocial model. However the chronic pain management strategy actually focussed on psychological approaches in preference to physical approaches. These approaches were utilised by all practitioners irrespective of their discipline. Consideration of social elements such as access to social support networks to support patients in managing their chronic pain was conspicuously absent from the approaches used. CONCLUSION: Pain clinic practitioners readily embraced cognitive/behavioural based management strategies but relatively little consideration to the impact social factors played in managing chronic pain was reported. Consequently multidisciplinary pain clinics espousing a bio-psychosocial model of pain management may not be achieving their maximum potential. PMID- 20298539 TI - PATCH: platelet transfusion in cerebral haemorrhage: study protocol for a multicentre, randomised, controlled trial. AB - BACKGROUND: Patients suffering from intracerebral haemorrhage have a poor prognosis, especially if they are using antiplatelet therapy. Currently, no effective acute treatment option for intracerebral haemorrhage exists. Limiting the early growth of intracerebral haemorrhage volume which continues the first hours after admission seems a promising strategy. Because intracerebral haemorrhage patients who are on antiplatelet therapy have been shown to be particularly at risk of early haematoma growth, platelet transfusion may have a beneficial effect. METHODS/DESIGN: The primary objective is to investigate whether platelet transfusion improves outcome in intracerebral haemorrhage patients who are on antiplatelet treatment. The PATCH study is a prospective, randomised, multi-centre study with open treatment and blind endpoint evaluation. Patients will be randomised to receive platelet transfusion within six hours or standard care. The primary endpoint is functional health after three months. The main secondary endpoints are safety of platelet transfusion and the occurrence of haematoma growth. To detect an absolute poor outcome reduction of 20%, a total of 190 patients will be included. DISCUSSION: To our knowledge this is the first randomised controlled trial of platelet transfusion for an acute haemorrhagic disease. PMID- 20298541 TI - Automatic colorimetric calibration of human wounds. AB - BACKGROUND: Recently, digital photography in medicine is considered an acceptable tool in many clinical domains, e.g. wound care. Although ever higher resolutions are available, reproducibility is still poor and visual comparison of images remains difficult. This is even more the case for measurements performed on such images (colour, area, etc.). This problem is often neglected and images are freely compared and exchanged without further thought. METHODS: The first experiment checked whether camera settings or lighting conditions could negatively affect the quality of colorimetric calibration. Digital images plus a calibration chart were exposed to a variety of conditions. Precision and accuracy of colours after calibration were quantitatively assessed with a probability distribution for perceptual colour differences (dE_ab). The second experiment was designed to assess the impact of the automatic calibration procedure (i.e. chart detection) on real-world measurements. 40 Different images of real wounds were acquired and a region of interest was selected in each image. 3 Rotated versions of each image were automatically calibrated and colour differences were calculated. RESULTS: 1st EXPERIMENT: Colour differences between the measurements and real spectrophotometric measurements reveal median dE_ab values respectively 6.40 for the proper patches of calibrated normal images and 17.75 for uncalibrated images demonstrating an important improvement in accuracy after calibration. The reproducibility, visualized by the probability distribution of the dE_ab errors between 2 measurements of the patches of the images has a median of 3.43 dE* for all calibrated images, 23.26 dE_ab for all uncalibrated images. If we restrict ourselves to the proper patches of normal calibrated images the median is only 2.58 dE_ab! Wilcoxon sum-rank testing (p < 0.05) between uncalibrated normal images and calibrated normal images with proper squares were equal to 0 demonstrating a highly significant improvement of reproducibility. In the second experiment, the reproducibility of the chart detection during automatic calibration is presented using a probability distribution of dE_ab errors between 2 measurements of the same ROI. CONCLUSION: The investigators proposed an automatic colour calibration algorithm that ensures reproducible colour content of digital images. Evidence was provided that images taken with commercially available digital cameras can be calibrated independently of any camera settings and illumination features. PMID- 20298542 TI - Self-organizing actin waves that simulate phagocytic cup structures. AB - This report deals with actin waves that are spontaneously generated on the planar, substrate-attached surface of Dictyostelium cells. These waves have the following characteristics. (1) They are circular structures of varying shape, capable of changing the direction of propagation. (2) The waves propagate by treadmilling with a recovery of actin incorporation after photobleaching of less than 10 seconds. (3) The waves are associated with actin-binding proteins in an ordered 3-dimensional organization: with myosin-IB at the front and close to the membrane, the Arp2/3 complex throughout the wave, and coronin at the cytoplasmic face and back of the wave. Coronin is a marker of disassembling actin structures. (4) The waves separate two areas of the cell cortex that differ in actin structure and phosphoinositide composition of the membrane. The waves arise at the border of membrane areas rich in phosphatidylinositol (3,4,5) trisphosphate (PIP3). The inhibition of PIP3 synthesis reversibly inhibits wave formation. (5) The actin wave and PIP3 patterns resemble 2-dimensional projections of phagocytic cups, suggesting that they are involved in the scanning of surfaces for particles to be taken up.PACS Codes: 87.16.Ln, 87.19.lp, 89.75.Fb. PMID- 20298543 TI - Resuscitation with low volume hydroxyethylstarch 130 kDa/0.4 is not associated with acute kidney injury. AB - INTRODUCTION: Acute kidney injury (AKI) in the ICU is associated with poorer prognosis. Hydroxyethylstarch (HES) solutions are fluid resuscitation colloids frequently used in the ICU with controversial nephrotoxic adverse effects. Our study objective was to evaluate HES impact on renal function and organ failures. METHODS: This observational retrospective study included 363 patients hospitalized for more than 72 hours in our ICU. A hundred and sixty eight patients received HES during their stay and 195 did not. We recorded patients' baseline characteristics on admission and type and volume of fluid resuscitation during the first 3 weeks of ICU stay. We also noted the evolution of urine output, the risk of renal dysfunction, injury to the kidney, failure of kidney function, loss of kidney function and end-stage kidney disease (RIFLE) classification and sepsis related organ failure assessment (SOFA) score over 3 weeks. RESULTS: Patients in the HES group were more severely ill on admission but AKI incidence was similar, as well as ICU mortality. The evolution of urine output (P = 0.74), RIFLE classification (P = 0.44) and SOFA score (P = 0.23) was not different. However, HES volumes administered were low (763+/-593 ml during the first 48 hours). CONCLUSIONS: Volume expansion with low volume HES 130 kDa/0.4 was not associated with AKI. PMID- 20298544 TI - Plasma selenium and risk of dysglycemia in an elderly French population: results from the prospective Epidemiology of Vascular Ageing Study. AB - BACKGROUND: A preventive role of selenium on the risk of diabetes has been reported and ascribed to the "insulin-like" activity of selenium and the antioxidant properties of the selenoenzymes. By contrast, data from cross sectional studies and clinical trials have suggested an adverse effect of high selenium status and selenium supplementation on type-2 diabetes risk. Given these controversial results, we investigated prospectively the relationship between baseline plasma selenium concentration and occurrence of dysglycemia (impaired fasting glucose or type 2 diabetes) in an elderly French cohort. METHODS: The Epidemiology of Vascular Ageing (EVA) study (n = 1389, 59-71 years) is a 9-year longitudinal study in which, fasting plasma glucose was measured at baseline, 2, 4 and 9 years. Analyses were performed on 1162 participants with complete data. RESULTS: At baseline plasma selenium mean levels were 1.08 (0.21) mumol/l in men and 1.10 (0.20) mumol/l in women. During the 9-year follow-up, 127 cases of dysglycemia occurred. A significant interaction was found between plasma selenium and sex. Risk of dysglycemia was significantly lower in men with plasma selenium in the highest tertile (T3:1.19-1.97) compared to those in the lowest tertile (T1:0.18-1.00) [HR = 0.48 (0.25-0.92)], but no significant relationship was observed in women. After controlling for socio-demographic factors, lifestyle factors, cardiovascular diseases, body mass index, hypertension and lipid profile, plasma selenium remained marginally significantly associated with occurrence of dysglycemia in men [T3 vs. T1, HR = 0.50 (0.24-1.04)] and unrelated in women. CONCLUSIONS: This prospective study suggests a sex-specific protective effect of higher selenium status at baseline on later occurrence of dysglycemia. PMID- 20298545 TI - Dietary meat fats and burden of cardiovascular disease risk factors, in the elderly: a report from the MEDIS study. AB - Dietary fats have long been associated with human health, and especially cardiovascular disease (CVD). Some observational studies have shown that reduction in dietary fats, and particularly cholesterol is associated with lower cardiovascular risk; however, other prospective studies or randomized controlled trials of dietary fat reduction or modification have shown varying results on CVD morbidity and mortality. In this work we evaluated the relationships between dietary fats and a cluster of CVD risk factors (i.e., diabetes, obesity, hypercholesterolemia, hypertension), among elderly individuals without known CVD. In particular, dietary and clinical data from 1486 elderly (aged 65 to 100 years) men and women living in Cyprus, Mitilini, Samothraki, Cephalonia, Crete, Lemnos, Syros, Naxos, Corfu and Zakynthos islands, and participated in the MEDIS study, were analysed. Data analysis revealed that 18.5% of males and 33.3% of females had three or four cardiovascular disease risk factors; the major source of fat was olive oil (mean intake for men and women 50.0 +/- 19.3 g/day and 46.0 +/- 16.8 g/day, p < 0.001). In addition it was observed that a 5% increase in energy adjusted fat intake from meat was associated with a 21% increase in the likelihood of having one additional CVD risk factor (95%CI 6%-39%); no significant associations were observed regarding the other types of fat consumed by the elderly participants. These findings may state a hypothesis that the consumption of fat only from meat or its products seems to increase the burden of CVD risk factors among CVD-free, elderly people. PMID- 20298546 TI - Choline PET based dose-painting in prostate cancer--modelling of dose effects. AB - BACKGROUND: Several randomized trials have documented the value of radiation dose escalation in patients with prostate cancer, especially in patients with intermediate risk profile. Up to now dose escalation is usually applied to the whole prostate. IMRT and related techniques currently allow for dose escalation in sub-volumes of the organ. However, the sensitivity of the imaging modality and the fact that small islands of cancer are often dispersed within the whole organ may limit these approaches with regard to a clear clinical benefit. In order to assess potential effects of a dose escalation in certain sub-volumes based on choline PET imaging a mathematical dose-response model was developed. METHODS: Based on different assumptions for alpha/beta, gamma 50, sensitivity and specificity of choline PET, the influence of the whole prostate and simultaneous integrated boost (SIB) dose on tumor control probability (TCP) was calculated. Based on the given heterogeneity of all potential variables certain representative permutations of the parameters were chosen and, subsequently, the influence on TCP was assessed. RESULTS: Using schedules with 74 Gy within the whole prostate and a SIB dose of 90 Gy the TCP increase ranged from 23.1% (high detection rate of choline PET, low whole prostate dose, high gamma 50/ASTRO definition for tumor control) to 1.4% TCP gain (low sensitivity of PET, high whole prostate dose, CN + 2 definition for tumor control) or even 0% in selected cases. The corresponding initial TCP values without integrated boost ranged from 67.3% to 100%. According to a large data set of intermediate-risk prostate cancer patients the resulting TCP gains ranged from 22.2% to 10.1% (ASTRO definition) or from 13.2% to 6.0% (CN + 2 definition). DISCUSSION: Although a simplified mathematical model was employed, the presented model allows for an estimation in how far given schedules are relevant for clinical practice. However, the benefit of a SIB based on choline PET seems less than intuitively expected. Only under the assumption of high detection rates and low initial TCP values the TCP gain has been shown to be relevant. CONCLUSIONS: Based on the employed assumptions, specific dose escalation to choline PET positive areas within the prostate may increase the local control rates. Due to the lack of exact PET sensitivity and prostate alpha/beta parameter, no firm conclusions can be made. Small variations may completely abrogate the clinical benefit of a SIB based on choline PET imaging. PMID- 20298548 TI - Gene regulatory networks modelling using a dynamic evolutionary hybrid. AB - BACKGROUND: Inference of gene regulatory networks is a key goal in the quest for understanding fundamental cellular processes and revealing underlying relations among genes. With the availability of gene expression data, computational methods aiming at regulatory networks reconstruction are facing challenges posed by the data's high dimensionality, temporal dynamics or measurement noise. We propose an approach based on a novel multi-layer evolutionary trained neuro-fuzzy recurrent network (ENFRN) that is able to select potential regulators of target genes and describe their regulation type. RESULTS: The recurrent, self-organizing structure and evolutionary training of our network yield an optimized pool of regulatory relations, while its fuzzy nature avoids noise-related problems. Furthermore, we are able to assign scores for each regulation, highlighting the confidence in the retrieved relations. The approach was tested by applying it to several benchmark datasets of yeast, managing to acquire biologically validated relations among genes. CONCLUSIONS: The results demonstrate the effectiveness of the ENFRN in retrieving biologically valid regulatory relations and providing meaningful insights for better understanding the dynamics of gene regulatory networks. The algorithms and methods described in this paper have been implemented in a Matlab toolbox and are available from: http://bioserver 1.bioacademy.gr/DataRepository/Project_ENFRN_GRN/. PMID- 20298547 TI - Development of proteoglycan-induced arthritis depends on T cell-supported autoantibody production, but does not involve significant influx of T cells into the joints. AB - INTRODUCTION: Inflammatory joint destruction in rheumatoid arthritis (RA) may be triggered by autoantibodies, the production of which is supported by autoreactive T cells. Studies on RA and animal models of the disease suggest that T cells recruited in the joints can locally initiate or propagate arthritis. Herein, we investigated the role of joint-homing versus lymphoid organ-homing T cells in the development of proteoglycan-induced arthritis (PGIA), an autoimmune model of RA. METHODS: To identify T cells migrating to the joints before and during development of autoimmune arthritis, we transferred fluorescence-labeled T cells, along with antigen-presenting cells, from BALB/c mice with PGIA to naive syngeneic severe combined immunodeficient (SCID) mice. We then monitored the recruitment of donor T cells in the ankle joints and joint-draining lymph nodes of the recipients using in vivo two-photon microscopy and ex vivo detection methods. To limit T-cell access to the joints, we selectively depleted T cells in the blood circulation by treatment with FTY720, an inhibitor of lymphocyte egress from lymphoid organs. Reduction of T cell presence in both lymphoid organs and blood was achieved by injection of donor cells from which T cells were removed prior to transfer. T and B cells were quantitated by flow cytometry, and antigen (PG)-specific responses were assessed by cell proliferation and serum antibody assays. RESULTS: Despite development of adoptively transferred arthritis in the recipient SCID mice, we found very few donor T cells in their joints after cell transfer. Treatment of recipient mice with FTY720 left the T-cell pool in the lymphoid organs intact, but reduced T cells in both peripheral blood and joints. However, FTY720 treatment failed to inhibit PGIA development. In contrast, arthritis was not seen in recipient mice after transfer of T cell-depleted cells from arthritic donors, and serum autoantibodies to PG were not detected in this group of mice. CONCLUSIONS: Our results suggest that antigen-specific T cells, which home to lymphoid organs and provide help to B cells for systemic autoantibody production, play a greater role in the development and progression of autoimmune arthritis than the small population of T cells that migrate to the joints. PMID- 20298549 TI - IgA anti-actin antibodies in children with celiac disease: comparison of immunofluorescence with Elisa assay in predicting severe intestinal damage. AB - BACKGROUND: Previous studies have demonstrated that the presence of serum IgA antibodies against actin filaments (AAA) in patients with celiac disease (CD) is strongly associated with mucosal damage and severe degrees of villous atrophy.The aims of the present study were (1) to verify the effectiveness of IgA-AAA in newly diagnosed CD patients in a clinical setting (2) to compare the immunofluorescence assay with ELISA assay; (3) to compare the correlation of our IgA anti-tissue transglutaminase antibodies (tTG-Ab) class with mucosal intestinal lesions. METHODS: 90 patients underwent endoscopy and multiple biopsies for suspected CD on the basis of symptoms, in presence of positive tTG Ab tests. Twenty biopsied and 25 not-biopsied subjects with negative tTG-Ab were tested as control groups. IgA-AAA assays were performed by indirect immunofluorescence using rat epithelial intestinal cells, and by ELISA with a commercial kit. tTG-Ab assay was a radio-binding assay. Intestinal specimens were collected by upper endoscopy and the histological study was done according to the Marsh's classification modified by Oberhuber (M/O). Auto-antibodies assays and histological evaluation have been performed blindly by skilled operators. RESULTS: CD diagnosis was confirmed in 82 patients (type I M/O in 2 patients, IIIA in 18 patients, IIIB in 29 patients and IIIC in 33 patients). Two patients with type 1 lesion in presence of positive tTG-Ab and abdominal complaints, started a gluten free diet. The rate of IgA-AAA positivity (sensitivity) by IFI and ELISA in histologically proven celiac disease patients, were 5.5% and 25% patients in IIIA, 27.5% and 34.4% patients in IIIB, 78.8% and 75% in IIIC patients, respectively.Patients with normal or nearly normal mucosa, regardless of tTG-Ab status, presented negative IgA-AAA IFI assay. On the other hand, 1 patient with normal mucosa but positive tTG-Ab, also presented positive IgA-AAA ELISA. All healthy non biopsied controls had negative IgA-AAA. tTG-Ab serum concentration was significantly correlated with more severe intestinal lesion (IIIB, IIIC M/O). CONCLUSIONS: IgA-AAA may be undetectable in presence of severe mucosal damage. Histology is still necessary to diagnose celiac disease and IgA AAA cannot be included in usual screening tests, because it has little to offer if compared to the well-established tTG-Ab.IgA-AAA could be an adjunctive, very useful tool to support the diagnosis of CD in case of suboptimal histology, when the biopsy is to be avoided for clinical reasons, or in case of negative parents' consensus. PMID- 20298550 TI - Long-term results of intensity-modulated radiotherapy concomitant with chemotherapy for hypopharyngeal carcinoma aimed at laryngeal preservation. AB - BACKGROUND: The objective of this retrospective study is to investigate laryngeal preservation and long-term treatment results in hypopharyngeal carcinoma treated with intensity-modulated radiotherapy (IMRT) combined with chemotherapy. METHODS: Twenty-seven patients with hypopharyngeal carcinoma (stage II-IV) were enrolled and underwent concurrent chemoradiotherapy. The chemotherapy regimens were monthly cisplatin and 5-fluorouracil for six patients and weekly cisplatin for 19 patients. All patients were treated with IMRT with simultaneous integrated boost technique. Acute and late toxicities were recorded based on CTCAE 3.0 (Common Terminology Criteria for Adverse Events). RESULTS: The median follow-up time for survivors was 53.0 months (range 36-82 months). The initial complete response rate was 85.2%, with a laryngeal preservation rate of 63.0%. The 5-year functional laryngeal, local-regional control, disease-free and overall survival rates were 59.7%, 63.3%, 51.0% and 34.8%, respectively. The most common greater than or equal to grade 3 acute and late effects were dysphagia (63.0%, 17 of 27 patients) and laryngeal stricture (18.5%, 5 of 27 patients), respectively. Patients belonging to the high risk group showed significantly higher risk of tracheostomy compared to the low risk group (p = 0.014). CONCLUSIONS: After long term follow-up, our results confirmed that patients with hypopharyngeal carcinoma treated with IMRT concurrent with platinum-based chemotherapy attain high functional laryngeal and local-regional control survival rates. However, the late effect of laryngeal stricture remains a problem, particularly for high risk group patients. PMID- 20298551 TI - Use of analgesics in intentional drug overdose presentations to hospital before and after the withdrawal of distalgesic from the Irish market. AB - BACKGROUND: Distalgesic, the prescription-only analgesic compound of paracetamol (325 mg) and dextropropoxyphene (32.5 mg) known as co-proxamol in the UK, was withdrawn from the Irish market as of January 2006. This study aimed to evaluate the impact of the withdrawal of distalgesic in terms of intentional drug overdose (IDO) presentations to hospital emergency departments (EDs) nationally. METHODS: A total of 42,849 IDO presentations to 37 of the 40 hospitals EDs operating in Ireland in 2003-2008 were recorded according to standardised procedures. Data on sales of paracetamol-containing drugs to retail pharmacies for the period 1998 2008 were obtained from IMS Health. RESULTS: The withdrawal of distalgesic from the Irish market resulted in an immediate reduction in sales to retail pharmacies from 40 million tablets in 2005 to 500,000 tablets in 2006 while there was a 48% increase in sales of other prescription compound analgesics. The rate of IDO presentations to hospital involving distalgesic in 2006-2008 was 84% lower than in the three years before it was withdrawn (10.0 per 100,000). There was a 44% increase in the rate of IDO presentations involving other prescription compound analgesics but the magnitude of this rate increase was five times smaller than the magnitude of the decrease in distalgesic-related IDO presentations. There was a decreasing trend in the rate of presentations involving any paracetamol containing drug that began in the years before the distalgesic withdrawal. CONCLUSIONS: The withdrawal of distalgesic has had positive benefits in terms of IDO presentations to hospital in Ireland and provides evidence supporting the restriction of availability of means as a prevention strategy for suicidal behaviour. PMID- 20298552 TI - Slit3 inhibits Robo3-induced invasion of synovial fibroblasts in rheumatoid arthritis. AB - INTRODUCTION: The repellent factor family of Slit molecules has been described to have repulsive function in the developing nervous system on growing axons expressing the Robo receptors. However, until today no data are available on whether these repellent factors are involved in the regulation of synovial fibroblast (SF) activity in rheumatoid arthritis (RA). METHODS: mRNA expression in primary synovial fibroblasts was quantified by quantitative reverse transcription PCR and protein expression was measured by fluorescence activated cell sorting (FACS) analysis. Different functional assays were performed with rheumatoid arthritis synovial fibroblasts (RASF): proliferation, migration and a novel in-vitro cartilage destruction assay. RESULTS: First, we found increased expression of Robo3 expression in RASF compared to normal SF. Interestingly, analysis of data from a recently published genome-wide association study suggests a contribution of ROBO3 gene polymorphisms to susceptibility of RA. Functional assays performed with RASF revealed induction of migration and cartilage destruction by Robo3 and increased matrix metalloproteinase (MMP)1 and MMP3 expression. Treatment of RASF in early passages with Slit3 led to inhibition of migration whereas RASF in later passages, having reduced Robo3 expression in cell culture, were not inhibited by Slit3 treatment. Here, reduction of Robo3 expression from passage 3 to 10 might reflect an important step in losing repulsive activity of Slit3. CONCLUSIONS: Taken together, our data showed that deregulation of the Robo3 receptor in synovial fibroblasts in RA correlates with aggressiveness of the fibroblasts. Slit3 reduces the migratory activity of synovial cells from patients with RA, potentially by repulsion of the cells in analogy to the neuronal system. Further studies will be necessary to prove Slit activity in vivo. PMID- 20298553 TI - Novel mutations underlying argininosuccinic aciduria in Saudi Arabia. AB - BACKGROUND: Argininosuccinic aciduria (ASAuria) is an autosomal recessive disorder of the urea cycle relatively common in Saudi Arabia as a consequence of extensive consanguinity. It is the most common urea cycle disorder identified in the Saudi population, which therefore prioritizes the need to delineate the underlying molecular defects leading to disease. FINDINGS: We utilized Whole Genome Amplification (WGA), PCR and direct sequencing to identify mutations underlying ASAuria cases diagnosed by our institution. A missense mutation that accounts for 50% of Saudi ASAuria patients was recently reported by our laboratory. In this study we report a further six novel mutations (and one previously reported) found in Saudi patients with ASAuria. The novel four missense, one nonsense and one splice-site mutation were confirmed by their absence in >300 chromosomes from the normal population. Pathogenicity of the novel splice-site mutation was also confirmed using reverse transcriptase-PCR analysis. Cross species amino acid conservation at the substituted residues described were observed in some but not all instances. CONCLUSIONS: Together, the eight mutations described by our laboratory, encompass >90% of ASAuria patients in Saudi Arabia and add to about 45 other ASAuria mutations reported worldwide. PMID- 20298554 TI - YODA: software to facilitate high-throughput analysis of chronological life span, growth rate, and survival in budding yeast. AB - BACKGROUND: The budding yeast Saccharomyces cerevisiae is one of the most widely studied model organisms in aging-related science. Although several genetic modifiers of yeast longevity have been identified, the utility of this system for longevity studies has been limited by a lack of high-throughput assays for quantitatively measuring survival of individual yeast cells during aging. RESULTS: Here we describe the Yeast Outgrowth Data Analyzer (YODA), an automated system for analyzing population survival of yeast cells based on the kinetics of outgrowth measured by optical density over time. YODA has been designed specifically for quantification of yeast chronological life span, but can also be used to quantify growth rate and survival of yeast cells in response to a variety of different conditions, including temperature, nutritional composition of the growth media, and chemical treatments. YODA is optimized for use with a Bioscreen C MBR shaker/incubator/plate reader, but is also amenable to use with any standard plate reader or spectrophotometer. CONCLUSIONS: We estimate that use of YODA as described here reduces the effort and resources required to measure chronological life span and analyze the resulting data by at least 15-fold. PMID- 20298555 TI - Comparative in vitro activity of Meropenem, Imipenem and Piperacillin/tazobactam against 1071 clinical isolates using 2 different methods: a French multicentre study. AB - BACKGROUND: Meropenem is a carbapenem that has an excellent activity against many gram-positive and gram-negative aerobic, facultative, and anaerobic bacteria. The major objective of the present study was to assess the in vitro activity of meropenem compared to imipenem and piperacillin/tazobactam, against 1071 non repetitive isolates collected from patients with bacteremia (55%), pneumonia (29%), peritonitis (12%) and wound infections (3%), in 15 French hospitals in 2006. The secondary aim of the study was to compare the results of routinely testings and those obtained by a referent laboratory. METHOD: Susceptibility testing and Minimum Inhibitory Concentrations (MICs) of meropenem, imipenem and piperacillin/tazobactam were determined locally by Etest method. Susceptibility to meropenem was confirmed at a central laboratory by disc diffusion method and MICs determined by agar dilution method for meropenem, imipenem and piperacillin/tazobactam. RESULTS: Cumulative susceptibility rates against Escherichia coli were, meropenem and imipenem: 100% and piperacillin/tazobactam: 90%. Against other Enterobacteriaceae, the rates were meropenem: 99%, imipenem: 98% and piperacillin/tazobactam: 90%. All Staphylococci, Streptococci and anaerobes were susceptible to the three antibiotics. Against non fermeters, meropenem was active on 84-94% of the strains, imipenem on 84-98% of the strains and piperacillin/tazobactam on 90-100% of the strains. CONCLUSIONS: Compared to imipenem, meropenem displays lower MICs against Enterobacteriaceae, Escherichia coli and Pseudomonas aeruginosa. Except for non fermenters, MICs90 of carbapenems were <4 mg/L. Piperacillin/tazobactam was less active against Enterobacteriaceae and Acinetobacter but not P. aeruginosa. Some discrepancies were noted between MICs determined by Etest accross centres and MICs determined by agar dilution method at the central laboratory. Discrepancies were more common for imipenem testing and more frequently related to a few centres. Overall MICs determined by Etest were in general higher (0.5 log to 1 log fold) than MICs by agar dilution. PMID- 20298556 TI - Use of Rasch methodology to develop a short version of the health related quality of life for eating disorders questionnaire: a prospective study. AB - BACKGROUND: To confirm the internal structure of the Health Related Quality of Life for Eating Disorders version 2 questionnaire (HeRQoLEDv2) and create and validate a shortened version (HeRQoLED-S). METHODS: 324 patients with eating disorders were assessed at baseline and one year later (75.6% of whom responded). We performed a confirmatory factor analysis of the HeRQoLEDv2 using baseline data, and then a Rasch analysis to shorten the questionnaire. Data obtained at year one was used to confirm the structure of the HeRQoLED short form and evaluate its validity and reliability. RESULTS: Two latent second-order factors - social maladjustment and mental health and functionality -- fit the data for the HeRQoLEDv2. Rasch analysis was computed separately for the two latent second order factors and shortened the HeRQoLEDv2 to 20 items. Infit and outfit indices were acceptable, with the confirmatory factor analysis of the HeRQoLED short form giving a root mean square error of approximation of 0.07, a non-normed fit index and a comparative fit index exceeding 0.90. The validity was also supported by the correlation with the convergent measures: the social maladjustment factor correlated 0.82 with the dieting concern factor of the Eating Attitudes Test-26 and the mental health and functionality factor correlated -0.69 with the mental summary component of the Short Form-12. Cronbach alphas exceeded 0.89. CONCLUSIONS: Two main factors, social maladjustment and mental health and functionality, explain the majority of HeRQoLEDv2 scores. The shortened version maintains good psychometric properties, though it must be validated in independent samples. PMID- 20298558 TI - Central blood pressure and pulse wave velocity: relationship to target organ damage and cardiovascular morbidity-mortality in diabetic patients or metabolic syndrome. An observational prospective study. LOD-DIABETES study protocol. AB - BACKGROUND: Diabetic patients show an increased prevalence of non-dipping arterial pressure pattern, target organ damage and elevated arterial stiffness. These alterations are associated with increased cardiovascular risk.The objectives of this study are the following: to evaluate the prognostic value of central arterial pressure and pulse wave velocity in relation to the incidence and outcome of target organ damage and the appearance of cardiovascular episodes (cardiovascular mortality, myocardial infarction, chest pain and stroke) in patients with type 2 diabetes mellitus or metabolic syndrome. METHODS/DESIGN: DESIGN: This is an observational prospective study with 5 years duration, of which the first year corresponds to patient inclusion and initial evaluation, and the remaining four years to follow-up. SETTING: The study will be carried out in the urban primary care setting. STUDY POPULATION: Consecutive sampling will be used to include patients diagnosed with type 2 diabetes between 20-80 years of age. A total of 110 patients meeting all the inclusion criteria and none of the exclusion criteria will be included. MEASUREMENTS: Patient age and sex, family and personal history of cardiovascular disease, and cardiovascular risk factors. Height, weight, heart rate and abdominal circumference. Laboratory tests: hemoglobin, lipid profile, creatinine, microalbuminuria, glomerular filtration rate, blood glucose, glycosylated hemoglobin, blood insulin, fibrinogen and high sensitivity C-reactive protein. Clinical and 24-hour ambulatory (home) blood pressure monitoring and self-measured blood pressure. Common carotid artery ultrasound for the determination of mean carotid intima-media thickness. Electrocardiogram for assessing left ventricular hypertrophy. Ankle-brachial index. Retinal vascular study based on funduscopy with non-mydriatic retinography and evaluation of pulse wave morphology and pulse wave velocity using the SphygmoCor system. The medication used for diabetes, arterial hypertension and hyperlipidemia will be registered, together with antiplatelet drugs. DISCUSSION: The results of this study will help to know and quantify the prognostic value of central arterial pressure and pulse wave velocity in relation to the evolution of the subclinical target organ damage markers and the possible incidence of cardiovascular events in patients with type 2 diabetes mellitus. PMID- 20298559 TI - Effects of UVB-induced oxidative stress on protein expression and specific protein oxidation in normal human epithelial keratinocytes: a proteomic approach. AB - BACKGROUND: The UVB component of solar ultraviolet irradiation is one of the major risk factors for the development of skin cancer in humans. UVB exposure elicits an increased generation of reactive oxygen species (ROS), which are responsible for oxidative damage to proteins, DNA, RNA and lipids. In order to examine the biological impact of UVB irradiation on skin cells, we used a parallel proteomics approach to analyze the protein expression profile and to identify oxidatively modified proteins in normal human epithelial keratinocytes. RESULTS: The expression levels of fifteen proteins - involved in maintaining the cytoskeleton integrity, removal of damaged proteins and heat shock response - were differentially regulated in UVB-exposed cells, indicating that an appropriate response is developed in order to counteract/neutralize the toxic effects of UVB-raised ROS. On the other side, the redox proteomics approach revealed that seven proteins - involved in cellular adhesion, cell-cell interaction and protein folding - were selectively oxidized. CONCLUSIONS: Despite a wide and well orchestrated cellular response, a relevant oxidation of specific proteins concomitantly occurs in UVB-irradiated human epithelial Keratinocytes. These modified (i.e. likely dysfunctional) proteins might result in cell homeostasis impairment and therefore eventually promote cellular degeneration, senescence or carcinogenesis. PMID- 20298557 TI - Group motivational intervention in overweight/obese patients in primary prevention of cardiovascular disease in the primary healthcare area. AB - BACKGROUND: The global mortality caused by cardiovascular disease increases with weight. The Framingham study showed that obesity is a cardiovascular risk factor independent of other risks such as type 2 diabetes mellitus, dyslipidemia and smoking. Moreover, the main problem in the management of weight-loss is its maintenance, if it is achieved. We have designed a study to determine whether a group motivational intervention, together with current clinical practice, is more efficient than the latter alone in the treatment of overweight and obesity, for initial weight loss and essentially to achieve maintenance of the weight achieved; and, secondly, to know if this intervention is more effective for reducing cardiovascular risk factors associated with overweight and obesity. METHODS: This 26-month follow up multi-centre trial, will include 1200 overweight/obese patients. Random assignment of the intervention by Basic Health Areas (BHA): two geographically separate groups have been created, one of which receives group motivational intervention (group intervention), delivered by a nurse trained by an expert phsychologist, in 32 group sessions, 1 to 12 fortnightly, and 13 to 32, monthly, on top of their standard program of diet, exercise, and the other (control group), receiving the usual follow up, with regular visits every 3 months. DISCUSSION: By addressing currently unanswered questions regarding the maintenance in weight loss in obesity/overweight, upon the expected completion of participant follow-up in 2012, the IMOAP trial should document, for the first time, the benefits of a motivational intervention as a treatment tool of weight loss in a primary care setting. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01006213. PMID- 20298560 TI - Randomised controlled trial of the effects of physical activity feedback on awareness and behaviour in UK adults: the FAB study protocol [ISRCTN92551397]. AB - BACKGROUND: While there are increasing data implicating poor recognition of physical inactivity as a potential barrier to healthy behaviour change, the efficacy of feedback to promote physical activity is uncertain. Using a randomised controlled trial nested within a population-based cohort study, we plan to test three variations of physical activity feedback against a control group. Our primary objective is to assess the efficacy of physical activity feedback in promoting physical activity behaviour change. Secondary objectives are to determine the influence of feedback on physical activity awareness and cognitions, and to compare behavioural effects by type of feedback. METHODS/DESIGN: We aim to recruit 500 healthy participants aged 30 to 55 years from the ongoing Fenland Study (Cambridge, UK). Following careful phenotyping during baseline measurement (anthropometric, clinical, body composition and fitness measurements, as well as questionnaires assessing self-reported and self rated physical activity, psychosocial correlates of physical activity behaviour, diet, lifestyle and general health), participants wear a combined heart rate and movement sensor (Actiheart(R)) for six continuous days and nights. After receipt of the physical activity data (around 2 weeks later), participants are randomly allocated to either a control group (no feedback) or one of three types of personalised physical activity feedback ('simple', 'visualised' or 'contextualised'), and complete repeat measures of self-rated physical activity and psychosocial correlates. Approximately five weeks after receiving feedback, all participants wear the Actiheart(R) for another six-day follow-up period and complete repeat questionnaires. Values at outcome, adjusted for baseline, will be compared between randomised groups. DISCUSSION: Given the randomised trial design and use of objective measure of physical activity, this study is likely to provide valuable insights into the efficacy of a feedback intervention in changing physical activity behaviour, as well as the psychological mechanisms involved. TRIAL REGISTRATION: Current Controlled Trials: ISRCTN92551397. PMID- 20298561 TI - Encephalomyocarditis virus infection in an Italian zoo. AB - A fatal Encephalomyocarditis virus (EMCV) infection epidemic involving fifteen primates occurred between October 2006 and February 2007 at the Natura Viva Zoo. This large open-field zoo park located near Lake Garda in Northern Italy hosts one thousand animals belonging to one hundred and fifty different species, including various lemur species. This lemur collection is the most relevant and rich in Italy. A second outbreak between September and November 2008 involved three lemurs. In all cases, the clinical signs were sudden deaths generally without any evident symptoms or only with mild unspecific clinical signs. Gross pathologic changes were characterized by myocarditis (diffuse or focal pallor of the myocardium), pulmonary congestion, emphysema, oedema and thoracic fluid. The EMCV was isolated and recognized as the causative agent of both outbreaks. The first outbreak in particular was associated with a rodent plague, confirming that rats are an important risk factor for the occurrence of the EMCV infection. PMID- 20298563 TI - Part I, patient perspective: activating patients to engage their providers in the use of evidence-based medicine: a qualitative evaluation of the VA Project to Implement Diuretics (VAPID). AB - BACKGROUND: This qualitative evaluation follows a randomized-control trial of a patient activation intervention in which hypertensive patients received a letter in the mail asking them to discuss thiazide diuretics with their provider. Results of the parent study indicated that the intervention was effective at facilitating discussions between patients and providers and enhancing thiazide prescribing rates. In the research presented here, our objective was to interview patients to determine their receptivity to patient activation, a potential leverage point for implementing interventions. METHODS: Semi-structured phone interviews were conducted with 54 patients, purposefully sampled from a randomized controlled trial of a patient activation intervention. All subjects had a history of hypertension and received primary care from one of twelve Veterans Affairs primary care clinics. All interviews were transcribed verbatim and reviewed by the interviewer. Interviews were independently coded by three qualitative researchers until consensus was attained, and relevant themes and responses were identified, grouped, and compared. NVivo 8.0 was used for data management and analysis. RESULTS: Data from this qualitative study revealed that most participants held favorable opinions toward the patient activation intervention used in the clinical trial. Most (82%) stated they had a positive reaction. Patients emphasized they liked the intervention because it was straightforward and encouraged them to initiate discussions with their provider. Also, by being active participants in their healthcare, patients felt more invested. Of the few patients offering negative feedback (11%), their main concern was discomfort with possibly challenging their providers' healthcare practices. Another outcome of interest was the patients' perceptions of why they were or were not prescribed a thiazide diuretic, for which several clinically relevant reasons were provided. CONCLUSION: Patients' perceptions of the intervention indicated it was effective via the encouragement of dialogue between themselves and their provider regarding evidence-based treatment options for hypertension. Additionally, patients' experiences with thiazide prescribing discussions shed light on the facilitators and barriers to implementing clinical practice guidelines regarding thiazides as first-line therapy for hypertension. TRIAL REGISTRATION: National Clinical Trial Registry number NCT00265538. PMID- 20298562 TI - A predictive computational model of the kinetic mechanism of stimulus-induced transducer methylation and feedback regulation through CheY in archaeal phototaxis and chemotaxis. AB - BACKGROUND: Photo- and chemotaxis of the archaeon Halobacterium salinarum is based on the control of flagellar motor switching through stimulus-specific methyl-accepting transducer proteins that relay the sensory input signal to a two component system. Certain members of the transducer family function as receptor proteins by directly sensing specific chemical or physical stimuli. Others interact with specific receptor proteins like the phototaxis photoreceptors sensory rhodopsin I and II, or require specific binding proteins as for example some chemotaxis transducers. Receptor activation by light or a change in receptor occupancy by chemical stimuli results in reversible methylation of glutamate residues of the transducer proteins. Both, methylation and demethylation reactions are involved in sensory adaptation and are modulated by the response regulator CheY. RESULTS: By mathematical modeling we infer the kinetic mechanisms of stimulus-induced transducer methylation and adaptation. The model (deterministic and in the form of ordinary differential equations) correctly predicts experimentally observed transducer demethylation (as detected by released methanol) in response to attractant and repellent stimuli of wildtype cells, a cheY deletion mutant, and a mutant in which the stimulated transducer species is methylation-deficient. CONCLUSIONS: We provide a kinetic model for signal processing in photo- and chemotaxis in the archaeon H. salinarum suggesting an essential role of receptor cooperativity, antagonistic reversible methylation, and a CheY-dependent feedback on transducer demethylation. PMID- 20298564 TI - Part II, provider perspectives: should patients be activated to request evidence based medicine? A qualitative study of the VA project to implement diuretics (VAPID). AB - BACKGROUND: Hypertension guidelines recommend the use of thiazide diuretics as first-line therapy for uncomplicated hypertension, yet diuretics are under prescribed, and hypertension is frequently inadequately treated. This qualitative evaluation of provider attitudes follows a randomized controlled trial of a patient activation strategy in which hypertensive patients received letters and incentives to discuss thiazides with their provider. The strategy prompted high discussion rates and enhanced thiazide-prescribing rates. Our objective was to interview providers to understand the effectiveness and acceptability of the intervention from their perspective, as well as the suitability of patient activation for more widespread guideline implementation. METHODS: Semi-structured phone interviews were conducted with 21 primary care providers. Interviews were transcribed verbatim and reviewed by the interviewer before being analyzed for content. Interviews were coded, and relevant themes and specific responses were identified, grouped, and compared. RESULTS: Of the 21 providers interviewed, 20 (95%) had a positive opinion of the intervention, and 18 of 20 (90%) thought the strategy was suitable for wider use. In explaining their opinions of the intervention, many providers discussed a positive effect on treatment, but they more often focused on the process of patient activation itself, describing how the intervention facilitated discussions by informing patients and making them more pro-active. Regarding effectiveness, providers suggested the intervention worked like a reminder, highlighted oversights, or changed their approach to hypertension management. Many providers also explained that the intervention 'aligned' patients' objectives with theirs, or made patients more likely to accept a change in medications. Negative aspects were mentioned infrequently, but concerns about the use of financial incentives were most common. Relevant barriers to initiating thiazide treatment included a hesitancy to switch medications if the patient was at or near goal blood pressure on a different anti hypertensive. CONCLUSIONS: Patient activation was acceptable to providers as a guideline implementation strategy, with considerable value placed on the activation process itself. By 'aligning' patients' objectives with those of their providers, this process also facilitated part of the effectiveness of the intervention. Patient activation shows promise for wider use as an implementation strategy, and should be tested in other areas of evidence-based medicine. TRIAL REGISTRATION: National Clinical Trial Registry number NCT00265538. PMID- 20298565 TI - Building capacity in health facility management: guiding principles for skills transfer in Liberia. AB - BACKGROUND: Management training is fundamental to developing human resources for health. Particularly as Liberia revives its health delivery system, facility and county health team managers are central to progress. Nevertheless, such management skills are rarely prioritized in health training, and sustained capacity building in this area is limited. We describe a health management delivery program in which a north and south institution collaborated to integrate classroom and field-based training in health management and to transfer the capacity for sustained management development in Liberia. METHODS: We developed and implemented a 6-month training program in health management skills (i.e. strategic problem solving, financial management, human resource management and leadership) delivered by Yale University and Mother Patern College from Liberia, with support from the Clinton HIV/AIDS Initiative. Over three 6-month cycles, responsibility for course instruction was transferred from the north institution to the south institution. A self-administered survey was conducted of all participants completing the course to measure changes in self-rated management skills, the degree to which the course was helpful and met its stated objectives, and faculty members' responsiveness to participant needs as the transfer process occurred. RESULTS: Respondents (n=93, response rate 95.9%) reported substantial improvement in self-reported management skills, and rated the helpfulness of the course and the degree to which the course met its objectives highly. Levels of improvement and course ratings were similar over the three cohorts as the course was transferred to the south institution. We suggest a framework of five elements for implementing successful management training programs that can be transferred and sustained in resource-limited settings, including: 1) use a short-course format focusing on four key skill areas with practical tools; 2) include didactic training, on-site projects, and on-site mentoring; 3) collaborate with an in country academic institution, willing and able to scale-up and maintain the training; 4) provide training for the in-country academic faculty; and 5) secure Ministry-level support to ensure participation. CONCLUSION: Our findings demonstrate key elements for scaling up and replicating educational initiatives that address management skills essential for long-term health systems strengthening in resource-poor settings. PMID- 20298566 TI - Proteome differences associated with fat accumulation in bovine subcutaneous adipose tissues. AB - BACKGROUND: The fat components of red meat products have been of interest to researchers due to the health aspects of excess fat consumption by humans. We hypothesized that differences in protein expression have an impact on adipose tissue formation during beef cattle development and growth. Therefore, in this study we evaluated the differences in the discernable proteome of subcutaneous adipose tissues of 35 beef crossbred steers [Charolais x Red Angus (CHAR) (n = 13) and Hereford x Angus (HEAN) (n = 22)] with different back fat (BF) thicknesses. The goal was to identify specific protein markers that could be associated with adipose tissue formation in beef cows. RESULTS: Approximately 541 580 protein spots were detected and compared in each crossbred group, and 33 and 36 protein spots showed expression differences between tissues with high and low BF thicknesses from HEAN and CHAR crossbed, respectively. The annexin 1 protein was highly expressed in both crossbred steers that had a higher BF thickness (p < 0.05) and this was further validated by a western blot analysis. In 13 tissues of CHAR animals and 22 tissues of HEAN animals, the relative expression of annexin 1 was significantly different (p < 0.05) between tissues with high and low BF thicknesses. CONCLUSION: The increased expression of annexin 1 protein has been found to be associated with higher BF thickness in both crossbred steers. This result lays the foundation for future studies to develop the protein marker for assessing animals with different BF thickness. PMID- 20298567 TI - Nrf2 protects against pulmonary fibrosis by regulating the lung oxidant level and Th1/Th2 balance. AB - BACKGROUND: Pulmonary fibrosis is a progressive and lethal disorder. Although the precise mechanisms of pulmonary fibrosis are not fully understood, oxidant/antioxidant and Th1/Th2 balances may play an important role in many of the processes of inflammation and fibrosis. The transcription factor Nrf2 acts as a critical regulator for various inflammatory and immune responses by controlling oxidative stress. We therefore investigated the protective role of Nrf2 against the development of pulmonary fibrosis. METHODS: To generate pulmonary fibrosis, both wild-type C57BL/6 mice and Nrf2-deficient mice of the same background were administered bleomycin intratracheally. RESULTS: The survival of Nrf2-deficient mice after bleomycin administration was significantly lower than that of wild type mice. The degree of bleomycin-induced initial pulmonary inflammation and pulmonary fibrosis was much more severe in Nrf2-deficient mice than in wild-type mice. The expression of antioxidant enzymes and phase II detoxifying enzymes was significantly reduced in the lungs of Nrf2-deficient mice, concomitant with an elevation of lung 8-isoprostane level, compared with wild-type mice. The expression of Th2 cytokines, such as interleukin-4 and interleukin-13, was significantly elevated in the lungs of Nrf2-deficient mice with an increase in the number of Th2 cells that express GATA-binding protein 3. CONCLUSIONS: The results indicated that Nrf2 protects against the development of pulmonary fibrosis by regulating the cellular redox level and lung Th1/Th2 balance. Thus, Nrf2 might be an important genetic factor in the determination of susceptibility to pulmonary fibrosis. PMID- 20298568 TI - Assessment of efficacy and tolerability of once-daily extended release metformin in patients with type 2 diabetes mellitus. AB - AIMS: To determine prospectively the efficacy, tolerability and patient satisfaction of an extended release formulation of metformin (metformin XR) in hospital based outpatients with type 2 diabetes mellitus currently treated with standard metformin. METHODS: Patients on immediate release standard metformin either alone or combined with other oral agents were switched to extended release metformin XR 500 mg tablets and titrated to a maximum dose of 2000 mg/day Measurements to include glucose and lipid control, blood pressure, body weight, waist circumference, C-reactive protein, adverse events and patient satisfaction were recorded at baseline, three and six months. RESULTS: Complete data were obtained for 35 of the 61 patients enrolled to the study. At three and six months no changes were reported for any of the cardiovascular risk factors except for lipids where there was a modest rise in plasma triglycerides. These effects were achieved with a reduced dose of metformin XR compared to pre-study dosing with standard metformin (1500 mg +/- 402 vs 1861 +/- 711 p = 0.004). A total of 77% of patients were free of gastrointestinal side effects and 83% of patients stated a preference for metformin XR at the end of the study. Ghost tablets were reported in the faeces by the majority of the patients (54.1%). CONCLUSIONS: Patients switched to extended release metformin XR derived the same clinical and metabolic benefits as for standard metformin but with reduced dosage, fewer gastrointestinal side effects and a greater sense of well being and satisfaction on medication. PMID- 20298569 TI - Augmented low-Dye tape alters foot mobility and neuromotor control of gait in individuals with and without exercise related leg pain. AB - BACKGROUND: Augmented low-Dye (ALD) tape is frequently used in the management of lower limb musculoskeletal pain and injury, yet our knowledge of its effect is incomplete, especially in regard to its neuromotor effects. METHODS: We measured electromyographic (EMG) activity of twelve lower limb muscles, three-dimensional kinematics of the ankle, knee, hip and pelvis, foot posture and foot mobility to determine the physiological effect of ALD tape. Fourteen females with exercise related leg pain and 14 matched asymptomatic females walked on a treadmill under three conditions: pre-tape, tape and post-tape. A series of repeated measure analysis of variance procedures were performed to investigate differences in EMG, kinematic, foot posture and mobility measurements. RESULTS: Application of ALD tape produced reductions in recruitment of tibialis anterior (7.3%) and tibialis posterior (6.9%). Large reductions in midfoot mobility (0.45 to 0.63 cm) and increases in arch height (0.58 cm), as well as moderate changes in ankle motion in the sagittal (2.0 to 5.3 degrees ) and transverse planes (4.0 to 4.3 degrees ) were observed. Reduced muscle activation (<3.0%) and increased motion (<1.7 degrees ) was observed at more proximal segments (knee, hip, pelvis) but were of smaller magnitude than at the foot and ankle. Changes in foot posture, foot mobility, ankle kinematics and leg muscle activity did not persist following the removal of ALD tape, but at more proximal segments small changes (<2.2 degrees , <5.4% maximum) continued to be observed following the removal of tape. There were no differences between groups. CONCLUSIONS: This study provides evidence that ALD tape influences muscle recruitment, movement patterns, foot posture and foot mobility. These effects occur in individuals with and without pain, and are dissipated up the kinetic chain. ALD tape should be considered in the management of individuals where increased arch height, reduced foot mobility, reduced ankle abduction and plantar flexion or reduced activation of leg muscles is desired. PMID- 20298570 TI - Synteny mapping between common bean and soybean reveals extensive blocks of shared loci. AB - BACKGROUND: Understanding syntentic relationship between two species is critical to assessing the potential for comparative genomic analysis. Common bean (Phaseolus vulgaris L.) and soybean (Glycine max L.), the two most important members of the Phaseoleae legumes, appear to have a diploid and polyploidy recent past, respectively. Determining the syntentic relationship between these two species will allow researchers to leverage not only genomic resources but also genetic data for important agronomic traits to improve both of these species. RESULTS: Genetically-positioned transcript loci of common bean were mapped relative to the recent soybean 1.01 pseudochromosome assembly. In nearly every case, each common bean locus mapped to two loci in soybean, a result consistent with the duplicate polyploidy history of soybean. Blocks of synteny averaging 32 cM in common bean and 4.9 Mb in soybean were observed for all 11 common bean linkage groups, and these blocks mapped to all 20 soybean pseudochromosomes. The median physical-to-genetic distance ratio in common bean (based on soybean physical distances) was approximately 120 kb/cM. approximately 15,000 common bean sequences (primarily EST contigs and EST singletons) were electronically positioned onto the common bean map using the shared syntentic blocks as references points. CONCLUSION: The collected evidence from this mapping strongly supports the duplicate history of soybean. It further provides evidence that the soybean genome was fractionated and reassembled at some point following the duplication event. These well mapped syntentic relationships between common bean and soybean will enable researchers to target specific genomic regions to discover genes or loci that affect phenotypic expression in both species. PMID- 20298571 TI - Effect on longitudinal growth and anemia of zinc or multiple micronutrients added to vitamin A: a randomized controlled trial in children aged 6-24 months. AB - BACKGROUND: The benefits of zinc or multiple micronutrient supplementations in African children are uncertain. African children may differ from other populations of children in developing countries because of differences in the prevalence of zinc deficiency, low birth weight and preterm delivery, recurrent or chronic infections such as HIV, or the quality of complementary diets and genetic polymorphisms affecting iron metabolism.The aim of this study was to ascertain whether adding zinc or multiple micronutrients to vitamin A supplementation improves longitudinal growth or reduces prevalence of anemia in children aged 6-24 months. METHODS: Randomized, controlled double-blinded trial of prophylactic micronutrient supplementation to children aged 6-24 months. Children in three cohorts - 32 HIV-infected children, 154 HIV-uninfected children born to HIV-infected mothers, and 187 uninfected children born to HIV-uninfected mothers - were separately randomly assigned to receive daily vitamin A (VA) [n = 124], vitamin A plus zinc (VAZ) [n = 123], or multiple micronutrients that included vitamin A and zinc (MM) [n = 126]. RESULTS: Among all children there were no significant differences between intervention arms in length-for-age Z scores (LAZ) changes over 18 months. Among stunted children (LAZ below -2) [n = 62], those receiving MM had a 0.7 Z-score improvement in LAZ versus declines of 0.3 in VAZ and 0.2 in VA (P = 0.029 when comparing effects of treatment over time). In the 154 HIV-uninfected children, MM ameliorated the effect of repeated diarrhea on growth. Among those experiencing more than six episodes, those receiving MM had no decline in LAZ compared to 0.5 and 0.6 Z-score declines in children receiving VAZ and VA respectively (P = 0.06 for treatment by time interaction). After 12 months, there was 24% reduction in proportion of children with anemia (hemoglobin below 11 g/dL) in MM arm (P = 0.001), 11% in VAZ (P = 0.131) and 18% in VA (P = 0.019). Although the within arm changes were significant; the between-group differences were not significant. CONCLUSIONS: Daily multiple micronutrient supplementation combined with vitamin A was beneficial in improving growth among children with stunting, compared to vitamin A alone or to vitamin A plus zinc. Effects on anemia require further study. TRIAL REGISTRATION: This study is registered with ClinicalTrials.gov, number. NCT00156832. PMID- 20298572 TI - The COSMIN checklist for evaluating the methodological quality of studies on measurement properties: a clarification of its content. AB - BACKGROUND: The COSMIN checklist (COnsensus-based Standards for the selection of health status Measurement INstruments) was developed in an international Delphi study to evaluate the methodological quality of studies on measurement properties of health-related patient reported outcomes (HR-PROs). In this paper, we explain our choices for the design requirements and preferred statistical methods for which no evidence is available in the literature or on which the Delphi panel members had substantial discussion. METHODS: The issues described in this paper are a reflection of the Delphi process in which 43 panel members participated. RESULTS: The topics discussed are internal consistency (relevance for reflective and formative models, and distinction with unidimensionality), content validity (judging relevance and comprehensiveness), hypotheses testing as an aspect of construct validity (specificity of hypotheses), criterion validity (relevance for PROs), and responsiveness (concept and relation to validity, and (in) appropriate measures). CONCLUSIONS: We expect that this paper will contribute to a better understanding of the rationale behind the items, thereby enhancing the acceptance and use of the COSMIN checklist. PMID- 20298573 TI - Evolving thermostability in mutant libraries of ligninolytic oxidoreductases expressed in yeast. AB - BACKGROUND: In the picture of a laboratory evolution experiment, to improve the thermostability whilst maintaining the activity requires of suitable procedures to generate diversity in combination with robust high-throughput protocols. The current work describes how to achieve this goal by engineering ligninolytic oxidoreductases (a high-redox potential laccase -HRPL- and a versatile peroxidase, -VP-) functionally expressed in Saccharomyces cerevisiae. RESULTS: Taking advantage of the eukaryotic machinery, complex mutant libraries were constructed by different in vivo recombination approaches and explored for improved stabilities and activities. A reliable high-throughput assay based on the analysis of T50 was employed for discovering thermostable oxidases from mutant libraries in yeast. Both VP and HRPL libraries contained variants with shifts in the T50 values. Stabilizing mutations were found at the surface of the protein establishing new interactions with the surrounding residues. CONCLUSIONS: The existing tradeoff between activity and stability determined from many point mutations discovered by directed evolution and other protein engineering means can be circumvented combining different tools of in vitro evolution. PMID- 20298574 TI - Anti-infective activity of apolipoprotein domain derived peptides in vitro: identification of novel antimicrobial peptides related to apolipoprotein B with anti-HIV activity. AB - BACKGROUND: Previous reports have shown that peptides derived from the apolipoprotein E receptor binding region and the amphipathic alpha-helical domains of apolipoprotein AI have broad anti-infective activity and antiviral activity respectively. Lipoproteins and viruses share a similar cell biological niche, being of overlapping size and displaying similar interactions with mammalian cells and receptors, which may have led to other antiviral sequences arising within apolipoproteins, in addition to those previously reported. We therefore designed a series of peptides based around either apolipoprotein receptor binding regions, or amphipathic alpha-helical domains, and tested these for antiviral and antibacterial activity. RESULTS: Of the nineteen new peptides tested, seven showed some anti-infective activity, with two of these being derived from two apolipoproteins not previously used to derive anti-infective sequences. Apolipoprotein J (151-170) - based on a predicted amphipathic alpha helical domain from apolipoprotein J - had measurable anti-HSV1 activity, as did apolipoprotein B (3359-3367) dp (apoBdp), the latter being derived from the LDL receptor binding domain B of apolipoprotein B. The more active peptide - apoBdp - showed similarity to the previously reported apoE derived anti-infective peptide, and further modification of the apoBdp sequence to align the charge distribution more closely to that of apoEdp or to introduce aromatic residues resulted in increased breadth and potency of activity. The most active peptide of this type showed similar potent anti-HIV activity, comparable to that we previously reported for the apoE derived peptide apoEdpL-W. CONCLUSIONS: These data suggest that further antimicrobial peptides may be obtained using human apolipoprotein sequences, selecting regions with either amphipathic alpha-helical structure, or those linked to receptor-binding regions. The finding that an amphipathic alpha helical region of apolipoprotein J has antiviral activity comparable with that for the previously reported apolipoprotein AI derived peptide 18A, suggests that full-length apolipoprotein J may also have such activity, as has been reported for full-length apolipoprotein AI. Although the strength of the anti-infective activity of the sequences identified was limited, this could be increased substantially by developing related mutant peptides. Indeed the apolipoprotein B derived peptide mutants uncovered by the present study may have utility as HIV therapeutics or microbicides. PMID- 20298575 TI - Neuropeptidomic analysis of the embryonic Japanese quail diencephalon. AB - BACKGROUND: Endogenous peptides such as neuropeptides are involved in numerous biological processes in the fully developed brain but very little is known about their role in brain development. Japanese quail is a commonly used bird model for studying sexual dimorphic brain development, especially adult male copulatory behavior in relation to manipulations of the embryonic endocrine system. This study uses a label-free liquid chromatography mass spectrometry approach to analyze the influence of age (embryonic days 12 vs 17), sex and embryonic day 3 ethinylestradiol exposure on the expression of multiple endogenous peptides in the developing diencephalon. RESULTS: We identified a total of 65 peptides whereof 38 were sufficiently present in all groups for statistical analysis. Age was the most defining variable in the data and sex had the least impact. Most identified peptides were more highly expressed in embryonic day 17. The top candidates for EE2 exposure and sex effects were neuropeptide K (downregulated by EE2 in males and females), gastrin-releasing peptide (more highly expressed in control and EE2 exposed males) and gonadotropin-inhibiting hormone related protein 2 (more highly expressed in control males and displaying interaction effects between age and sex). We also report a new potential secretogranin-2 derived neuropeptide and previously unknown phosphorylations in the C-terminal flanking protachykinin 1 neuropeptide. CONCLUSIONS: This study is the first larger study on endogenous peptides in the developing brain and implies a previously unknown role for a number of neuropeptides in middle to late avian embryogenesis. It demonstrates the power of label-free liquid chromatography mass spectrometry to analyze the expression of multiple endogenous peptides and the potential to detect new putative peptide candidates in a developmental model. PMID- 20298576 TI - Antibodies against multiple merozoite surface antigens of the human malaria parasite Plasmodium falciparum inhibit parasite maturation and red blood cell invasion. AB - BACKGROUND: Plasmodium falciparum merozoites expose at their surface a large protein complex, which is composed of fragments of merozoite surface protein 1 (MSP-1; called MSP-183, MSP-130, MSP-138, and MSP-142) plus associated processing products of MSP-6 and MSP-7. During erythrocyte invasion this complex, as well as an integral membrane protein called apical membrane antigen-1 (AMA-1), is shed from the parasite surface following specific proteolysis. Components of the MSP 1/6/7 complex and AMA-1 are presently under development as malaria vaccines. METHODS: The specificities and effects of antibodies directed against MSP-1, MSP 6, MSP-7 on the growth of blood stage parasites were studied using ELISA and the pLDH-assay. To understand the mode of action of these antibodies, their effects on processing of MSP-1 and AMA-1 on the surface of merozoites were investigated. RESULTS: Antibodies targeting epitopes located throughout the MSP-1/6/7 complex interfere with shedding of MSP-1, and as a consequence prevent erythrocyte invasion. Antibodies targeting the MSP-1/6/7 complex have no effect on the processing and shedding of AMA-1 and, similarly, antibodies blocking the shedding of AMA-1 do not affect cleavage of MSP-1, suggesting completely independent functions of these proteins during invasion. Furthermore, some epitopes, although eliciting highly inhibitory antibodies, are only poorly recognized by the immune system when presented in the structural context of the intact antigen. CONCLUSIONS: The findings reported provide further support for the development of vaccines based on MSP-1/6/7 and AMA-1, which would possibly include a combination of these antigens. PMID- 20298577 TI - Theoretical analysis of the mechanisms of a gender differentiation in the propensity for orthostatic intolerance after spaceflight. AB - BACKGROUND: A tendency to develop reentry orthostasis after a prolonged exposure to microgravity is a common problem among astronauts. The problem is 5 times more prevalent in female astronauts as compared to their male counterparts. The mechanisms responsible for this gender differentiation are poorly understood despite many detailed and complex investigations directed toward an analysis of the physiologic control systems involved. METHODS: In this study, a series of computer simulation studies using a mathematical model of cardiovascular functioning were performed to examine the proposed hypothesis that this phenomenon could be explained by basic physical forces acting through the simple common anatomic differences between men and women. In the computer simulations, the circulatory components and hydrostatic gradients of the model were allowed to adapt to the physical constraints of microgravity. After a simulated period of one month, the model was returned to the conditions of earth's gravity and the standard postflight tilt test protocol was performed while the model output depicting the typical vital signs was monitored. CONCLUSIONS: The analysis demonstrated that a 15% lowering of the longitudinal center of gravity in the anatomic structure of the model was all that was necessary to prevent the physiologic compensatory mechanisms from overcoming the propensity for reentry orthostasis leading to syncope. PMID- 20298579 TI - Bentall procedure 39 years after implantation of a Starr-Edwards aortic caged ball-valve prosthesis. AB - We report a case of a male patient who received an implantation of a Starr Edwards-caged-ball-valve-prosthesis in 1967. The surgery and postoperative course were without complications and the patient recovered well after the operation. For the next four decades, the patient remained asymptomatic--no restrictions on his lifestyle and without any complications. In 2006, 39 years after the initial operation, we performed a Bentall-Procedure to treat an aortic ascendens aneurysm with diameters of 6.0 x 6.5 cm: we explanted the old Starr-Edwards-aortic-caged ball-valve-prosthesis and replaced the ascending aorta with a 29 mm St.Jude Medical aortic-valve-composite-graft and re-implanted the coronary arteries.This case represents the longest time period between Starr-Edwards-caged-ball-valve prosthesis-implantation and Bentall-reoperation, thereby confirming the excellent durability of this valve. PMID- 20298580 TI - Novel model for end-neuroma formation in the amputated rabbit forelimb. AB - BACKGROUND: The forelimb amputee poses many reconstructive challenges in the clinical setting, and there is a paucity of established surgical models for study. To further elucidate the pathogenic process in amputation neuroma formation, we created a reproducible, well-tolerated rabbit forelimb amputation model. METHODS: Upon approval from the Institutional Animal Care and Use Committee, 5 New Zealand White rabbits underwent left forelimb amputation. During this initial surgery, the median, radial and ulnar nerves were transected 1.6-2.5 (mean 2.0) cm distal to the brachial plexus, transposed onto the anterior chest wall and preserved at length. Six weeks subsequent to the amputation, the distal 5 mm of each neuroma was excised, and the remaining stump underwent histomorphometric analysis. RESULTS: The nerve cross sectional areas increased by factors of 1.99, 3.17, and 2.59 in the median (p = 0.077), radial (p < 0.0001) and the ulnar (p = 0.0026) nerves, respectively. At the axonal level, the number and cross-sectional area of myelinated fibers demonstrated an inverse relationship whereby the number of myelinated fibers in the median, radial and ulnar nerves increased by factors of 5.13 (p = 0.0043), 5.25 (p = 0.0056) and 5.59 (p = 0.0027), and the cross-sectional areas of these myelinated fibers decreased by factors of 4.62 (p < 0.001), 3.51 (p < 0.01), and 4.29 (p = 0.0259), respectively. CONCLUSION: Given that the surgical model appears well-tolerated by the rabbits and that patterns of morphologic change are consistent and reproducible, we are encouraged to further investigate the utility of this model in the pathogenesis of neuroma formation. PMID- 20298578 TI - EEG alpha phenotypes: linkage analyses and relation to alcohol dependence in an American Indian community study. AB - BACKGROUND: Evidence for a high degree of heritability of EEG alpha phenotypes has been demonstrated in twin and family studies in a number of populations. However, information on linkage of this phenotype to specific chromosome locations is still limited. This study's aims were to map loci linked to EEG alpha phenotypes and to determine if there was overlap with loci previously mapped for alcohol dependence in an American Indian community at high risk for substance dependence. METHODS: Each participant gave a blood sample and completed a structured diagnostic interview using the Semi Structured Assessment for the Genetics of Alcoholism. Bipolar EEGs were collected and spectral power determined in the alpha (7.5-12.0 Hz) frequency band for two composite scalp locations previously identified by principal components analyses (bilateral fronto-central and bilateral centro-parietal-occipital). Genotypes were determined for a panel of 791 micro-satellite polymorphisms in 410 members of multiplex families using SOLAR. RESULTS: Sixty percent of this study population had a lifetime diagnosis of alcohol dependence. Analyses of multipoint variance component LOD scores, for the EEG alpha power phenotype, revealed two loci that had a LOD score of 3.0 or above for the fronto-central scalp region on chromosomes 1 and 6. Additionally, 4 locations were identified with LOD scores above 2.0 on chromosomes 4, 11, 14, 16 for the fronto-central location and one on chromosome 2 for the centro-parietal occipital location. CONCLUSION: These results corroborate the importance of regions on chromosome 4 and 6 highlighted in prior segregation studies in this and other populations for alcohol dependence-related phenotypes, as well as other areas that overlap with other substance dependence phenotypes identified in previous linkage studies in other populations. These studies additionally support the construct that EEG alpha recorded from fronto-central scalp areas may represent an important endophenotype associated with alcohol and other substance dependence. PMID- 20298581 TI - Role of adiponectin and leptin on body development in infants during the first year of life. AB - BACKGROUND: The control of growth and nutritional status in the foetus and neonate is a complex mechanism, in which also hormones produced by adipose tissue, such as adiponectin and leptin are involved. The aim of this study was to evaluate levels of adiponectin, leptin and insulin in appropriate (AGA) and small for gestational age (SGA) children during the 1st year of life and to correlate these with auxological parameters. METHODS: In 33 AGA and 29 SGA infants, weight, length, head circumference, glucose, insulin, adiponectin and leptin levels were evaluated at the second day of life, and at one, six and twelve months, during which a portion of SGA could show catch-up growth (rapid growth in infants born small for their gestational age). RESULTS: Both total and isoform adiponectin levels were comparable between AGA and SGA infants at birth and until age one year. These levels significantly increased from birth to the first month of life and then decreased to lower values at 1 year of age in all subjects. Circulating leptin concentrations were higher in AGA (2.1 +/- 4.1 ng/ml) than in SGA neonates (0.88 +/- 1.03 ng/ml, p < 0.05) at birth, then similar at the 1st and the 6th month of age, but they increased in SGA from six months to one year, when they showed catch-up growth. Circulating insulin levels were not statistically different in AGA and SGA neonates at any study time point. Insulin levels in both AGA and SGA infants increased over the study period, and were significantly lower at birth compared to one, six and 12 months of age. CONCLUSIONS: During the first year of life, in both AGA and SGA infants a progressive decrease in adiponectin levels was observed, while a difference in leptin values was correlated with the nutritional status. PMID- 20298582 TI - Can we rely on the best trial? A comparison of individual trials and systematic reviews. AB - BACKGROUND: The ideal evidence to answer a question about the effectiveness of treatment is a systematic review. However, for many clinical questions a systematic review will not be available, or may not be up to date. One option could be to use the evidence from an individual trial to answer the question? METHODS: We assessed how often (a) the estimated effect and (b) the p-value in the most precise single trial in a meta-analysis agreed with the whole meta analysis. For a random sample of 200 completed Cochrane Reviews (January, 2005) we identified a primary outcome and extracted: the number of trials, the statistical weight of the most precise trial, the estimate and confidence interval for both the highest weighted trial and the meta-analysis overall. We calculated the p-value for the most precise trial and meta-analysis. RESULTS: Of 200 reviews, only 132 provided a meta-analysis of 2 or more trials, with a further 35 effect estimates based on single trials. The average number of trials was 7.3, with the most precise trial contributing, on average, 51% of the statistical weight to the summary estimate from the whole meta-analysis. The estimates of effect from the most precise trial and the overall meta-analyses were highly correlated (rank correlation of 0.90).There was an 81% agreement in statistical conclusions. Results from the most precise trial were statistically significant in 60 of the 167 evaluable reviews, with 55 of the corresponding systematic reviews also being statistically significant. The five discrepant results were not strikingly different with respect to their estimates of effect, but showed considerable statistical heterogeneity between trials in these meta analyses. However, among the 101 cases in which the most precise trial was not statistically significant, the corresponding meta-analyses yielded 31 statistically significant results. CONCLUSIONS: Single most precise trials provided similar estimates of effects to those of the meta-analyses to which they contributed, and statistically significant results are generally in agreement. However, "negative" results were less reliable, as may be expected from single underpowered trials. For systematic reviewers we suggest that: (1) key trial(s) in a review deserve greater attention (2) systematic reviewers should check agreement of the most precise trial and the meta analysis. For clinicians using trials we suggest that when a meta-analysis is not available, a focus on the most precise trial is reasonable provided it is adequately powered. PMID- 20298583 TI - Association of IL-4RA single nucleotide polymorphisms, HLA-DR and HLA-DQ in children with Alternaria-sensitive moderate-severe asthma. AB - BACKGROUND: Asthma afflicts 6% to 8% of the United States population, and severe asthma represents approximately 10% of asthmatic patients. Several epidemiologic studies in the United States and Europe have linked Alternaria sensitivity to both persistence and severity of asthma. In order to begin to understand genetic risk factors underlying Alternaria sensitivity and asthma, in these studies we examined T cell responses to Alternaria antigens, HLA Class II restriction and HLA-DQ protection in children with severe asthma. METHODS: Sixty children with Alternaria-sensitive moderate-severe asthma were compared to 49 children with Alternaria-sensitive mild asthma. We examined HLA-DR and HLA-DQ frequencies in Alternaria-sensitive asthmatic by HLA typing. To determine ratios of Th1/Th2 Alternaria-specific T-cells, cultures were stimulated in media alone, Alternaria alternata extract and Alt a1. Sensitivity to IL-4 stimulation was measured by up regulation of CD23 on B cells. RESULTS: Children with Alternaria-sensitive moderate-severe asthma trended to have increased sensitivities to Cladosporium (46% versus 35%), to Aspergillus (43% versus 28%), and significantly increased sensitivities to trees (78% versus 57%) and to weeds (68% versus 48%). The IL-4RA ile75val polymorphism was significantly increased in Alternaria-sensitive moderate-severe asthmatics, 83% (0.627 allele frequency) compared to Alternaria sensitive mild asthmatics, 57% (0.388 allele frequency). This was associated with increased sensitivity to IL-4 stimulation measured by significantly increased IL 4 stimulated CD23 expression on CD19+ and CD86+CD19+ B cells of Alternaria sensitive moderate-severe asthmatics. IL-5 and IL-13 synthesis was significantly increased in Alternaria-sensitive moderate-severe asthmatics compared to mild asthmatics to Alternaria extract and Alt a1 stimulation. The frequency of HLA DQB1*03 allele was significantly decreased in Alternaria-sensitive moderate severe asthmatics compared to mild asthmatics, 39% versus 63%, with significantly decreased allele frequency, 0.220 versus 0.398. SUMMARY: In children with Alternaria-sensitive moderate severe asthma, there was an increased Th2 response to Alternaria stimulation and increased sensitivity to IL-4 stimulation. This skewing towards a Th2 response was associated with an increased frequency of the IL-4RA ile75val polymorphism. In evaluating the HLA association, there was a decreased frequency of HLA-DQB1*03 in Alternaria-sensitive moderate severe asthmatic children consistent with previous studies suggest that HLA-DQB1*03 may be protective against the development of mold-sensitive severe asthma. PMID- 20298584 TI - MISHIMA--a new method for high speed multiple alignment of nucleotide sequences of bacterial genome scale data. AB - BACKGROUND: Large nucleotide sequence datasets are becoming increasingly common objects of comparison. Complete bacterial genomes are reported almost everyday. This creates challenges for developing new multiple sequence alignment methods. Conventional multiple alignment methods are based on pairwise alignment and/or progressive alignment techniques. These approaches have performance problems when the number of sequences is large and when dealing with genome scale sequences. RESULTS: We present a new method of multiple sequence alignment, called MISHIMA (Method for Inferring Sequence History In terms of Multiple Alignment), that does not depend on pairwise sequence comparison. A new algorithm is used to quickly find rare oligonucleotide sequences shared by all sequences. Divide and conquer approach is then applied to break the sequences into fragments that can be aligned independently by an external alignment program. These partial alignments are assembled together to form a complete alignment of the original sequences. CONCLUSIONS: MISHIMA provides improved performance compared to the commonly used multiple alignment methods. As an example, six complete genome sequences of bacteria species Helicobacter pylori (about 1.7 Mb each) were successfully aligned in about 6 hours using a single PC. PMID- 20298585 TI - Late presentation of a mucinous ovarian adenocarcinoma which was initially diagnosed as a primary pancreatic carcinoma: a case report and review of the literature. AB - INTRODUCTION: Adenocarcinoma of the ovary is an aggressive neoplasm which often metastasizes to the lung or liver. Metastases rarely occur to the pancreas, but a tissue diagnosis is required to confirm this event. Although most tumors of the pancreas are primary pancreatic neoplasms, metastatic lesions have been reported most commonly as arising from renal cell carcinoma. CASE PRESENTATION: We report the case of a 51-year-old Caucasian woman with ovarian mucinous adenocarcinoma with metastasis to the head of the pancreas that was originally misdiagnosed as a pancreatic primary tumor. CONCLUSION: Mucinous ovarian adenocarcinomas rarely metastasize to the pancreas. New pancreatic lesions should be investigated through tissue biopsy and tumor markers, while keeping an open-minded differential diagnosis to avoid a misdiagnosis or a delay in treatment. PMID- 20298586 TI - Advantages of the single delay model for the assessment of insulin sensitivity from the intravenous glucose tolerance test. AB - BACKGROUND: The Minimal Model, (MM), used to assess insulin sensitivity (IS) from Intra-Venous Glucose-Tolerance Test (IVGTT) data, suffers from frequent lack of identifiability (parameter estimates with Coefficients of Variation (CV) less than 52%). The recently proposed Single Delay Model (SDM) is evaluated as a practical alternative. METHODS: The SDM was applied to 74 IVGTTs from lean (19), overweight (22), obese (22) and morbidly obese (11) subjects. Estimates from the SDM (K xgI) were compared with the corresponding MM (S I), 1/HOMA-IR index and Euglycemic-Hyperinsulinemic Clamp (M-EHC over 7 subjects) estimates. RESULTS: K xgI was identifiable in 73 out of 74 subjects (CV = 69% in the 74 th subject) and ranged from 1.25 x 10(-5) to 4.36 x 10(-4) min(-1) pM(-1); S I CV was >52% in 36 subjects (up to 2.36 x 10(9)%) and presented 18 extreme values (or= 3.99). K xgI correlated well with 1/HOMA-IR (r = 0.56, P < 0.001), whereas the correlations K xgI-S I and 1/HOMA-IR-S I were high (r = 0.864 and 0.52 respectively) and significant (P < 0.001 in both cases) only in the non extreme SI sub-sample (56 subjects). Correlations K xgI vs. M-EHC and SI vs. M EHC were positive (r = 0.92, P = 0.004 and r = 0.83, P = 0.02 respectively). K xgI decreased for higher BMI's (P < 0.001), SI significantly so only over the non extreme-SI sub-sample. The Acute Insulin Response Index was also computed and the expected inverse (hyperbolic) relationship with the K xgI observed. CONCLUSIONS: Precise estimation of insulin sensitivity over a wide range of BMI, stability of all other model parameters, closer adherence to accepted physiology make the SDM a useful alternative tool for the evaluation of insulin sensitivity from the IVGTT. PMID- 20298587 TI - Effect of day-to-day variations in adrenal cortex hormone levels on abdominal symptoms. AB - INTRODUCTION: The hypothalamic-pituitary-adrenal axis is known to be related to abdominal symptoms, and the relationship between abdominal pain and cortisol secretory patterns has been previously investigated using a cross-sectional approach. Here, we investigated the effect of day-to-day variations in salivary cortisol and dehydroepiandrosterone-sulfate levels on abdominal symptoms in healthy individuals. METHODS: Eleven college students (4 males and 7 females) participated in this study. The participants were asked to collect their saliva immediately after awakening and before bedtime for eight consecutive days. They also completed a questionnaire about abdominal symptoms before bedtime. The linear mixed model was applied to analyze the effects of the day-by-day variability or the 8-day average adrenal hormone level (at awakening, before bedtime, slope from awakening to bedtime) on abdominal symptoms. RESULTS: The day to-day variability of cortisol levels before bedtime was negatively related with loose stool, while the day-to-day variability of the cortisol slope was positively correlated with loose stool. A low 8-day average dehydroepiandrosterone-sulfate level at awakening was positively related with frequent bowel movements, loose stool, and long bouts of severe abdominal pain. Likewise, a low 8-day average dehydroepiandrosterone-sulfate slope was positively related with long bouts of abdominal pain. CONCLUSIONS: Low cortisol levels before bedtime and a steeper diurnal cortisol slope during the day may be related to bouts of diarrhea during the day. PMID- 20298588 TI - Performance evaluation of commercial miRNA expression array platforms. AB - BACKGROUND: microRNAs (miRNA) are short, endogenous transcripts that negatively regulate the expression of specific mRNA targets. The relative abundance of miRNAs is linked to function in vivo and miRNA expression patterns are potentially useful signatures for the development of diagnostic, prognostic and therapeutic biomarkers. FINDING: We compared the performance characteristics of four commercial miRNA array technologies and found that all platforms performed well in separate measures of performance. CONCLUSIONS: The Ambion and Agilent platforms were more accurate, whereas the Illumina and Exiqon platforms were more specific. Furthermore, the data analysis approach had a large impact on the performance, predominantly by improving precision. PMID- 20298589 TI - Coregulation mapping based on individual phenotypic variation in response to virus infection. AB - BACKGROUND: Gene coregulation across a population is an important aspect of the considerable variability of the human immune response to virus infection. Methodology to investigate it must rely on a number of ingredients ranging from gene clustering to transcription factor enrichment analysis. RESULTS: We have developed a methodology to investigate the gene to gene correlations for the expression of 34 genes linked to the immune response of Newcastle Disease Virus (NDV) infected conventional dendritic cells (DCs) from 145 human donors. The levels of gene expression showed a large variation across individuals. We generated a map of gene co-expression using pairwise correlation and multidimensional scaling (MDS). The analysis of these data showed that among the 13 genes left after filtering for statistically significant variations, two clusters are formed. We investigated to what extent the observed correlation patterns can be explained by the sharing of transcription factors (TFs) controlling these genes. Our analysis showed that there was a significant positive correlation between MDS distances and TF sharing across all pairs of genes. We applied enrichment analysis to the TFs having binding sites in the promoter regions of those genes. This analysis, after Gene Ontology filtering, indicated the existence of two clusters of genes (CCL5, IFNA1, IFNA2, IFNB1) and (IKBKE, IL6, IRF7, MX1) that were transcriptionally co-regulated. In order to facilitate the use of our methodology by other researchers, we have also developed an interactive coregulation explorer web-based tool called CorEx. It permits the study of MDS and hierarchical clustering of data combined with TF enrichment analysis. We also offer web services that provide programmatic access to MDS, hierarchical clustering and TF enrichment analysis. CONCLUSIONS: MDS mapping based on correlation in conjunction with TF enrichment analysis represents a useful computational method to generate predictions underlying gene coregulation across a population. PMID- 20298590 TI - Lovastatin induces apoptosis of ovarian cancer cells and synergizes with doxorubicin: potential therapeutic relevance. AB - BACKGROUND: Ovarian carcinoma is a rarely curable disease, for which new treatment options are required. As agents that block HMG-CoA reductase and the mevalonate pathway, the statin family of drugs are used in the treatment of hypercholesterolemia and have been shown to trigger apoptosis in a tumor-specific manner. Recent clinical trials show that the addition of statins to traditional chemotherapeutic strategies can increase efficacy of targeting statin-sensitive tumors. Our goal was to assess statin-induced apoptosis of ovarian cancer cells, either alone or in combination with chemotherapeutics, and then determine these mechanisms of action. METHODS: The effect of lovastatin on ovarian cancer cell lines was evaluated alone and in combination with cisplatin and doxorubicin using several assays (MTT, TUNEL, fixed PI, PARP cleavage) and synergy determined by evaluating the combination index. The mechanisms of action were evaluated using functional, molecular, and pharmacologic approaches. RESULTS: We demonstrate that lovastatin induces apoptosis of ovarian cancer cells in a p53-independent manner and synergizes with doxorubicin, a chemotherapeutic agent used to treat recurrent cases of ovarian cancer. Lovastatin drives ovarian tumor cell death by two mechanisms: first, by blocking HMG-CoA reductase activity, and second, by sensitizing multi-drug resistant cells to doxorubicin by a novel mevalonate independent mechanism. This inhibition of drug transport, likely through inhibition of P-glycoprotein, potentiates both DNA damage and tumor cell apoptosis. CONCLUSIONS: The results of this research provide pre-clinical data to warrant further evaluation of statins as potential anti-cancer agents to treat ovarian carcinoma. Many statins are inexpensive, off-patent generic drugs that are immediately available for use as anti-cancer agents. We provide evidence that lovastatin triggers apoptosis of ovarian cancer cells as a single agent by a mevalonate-dependent mechanism. Moreover, we also show lovastatin synergizes with doxorubicin, an agent administered for recurrent disease. This synergy occurs by a novel mevalonate-independent mechanism that antagonizes drug resistance, likely by inhibiting P-glycoprotein. These data raise important issues that may impact how statins can best be included in chemotherapy regimens. PMID- 20298591 TI - Enoxaparin, effective dosage for intensive care patients: double-blinded, randomised clinical trial. AB - INTRODUCTION: Intensive care unit (ICU) patients are predisposed to thromboembolism. Routine prophylactic anticoagulation is widely recommended. Low molecular-weight heparins, such as enoxaparin, are increasingly used because of predictable pharmacokinetics. This study aims to determine the subcutaneous (SC) dose of enoxaparin that would give the best anti-factor Xa levels in ICU patients. METHODS: The 72 patients admitted to a mixed ICU at Odense University Hospital (OUH) in Denmark were randomised into four groups to receive 40, 50, 60, or 70 mg SC enoxaparin for a period of 24 hours. Anti-factor Xa activity (aFXa) was measured before, and at 4, 12, and 24 hours after administration. An AFXa level between 0.1 to 0.3 IU/ml was considered evidence of effective antithrombotic activity. RESULTS: Median peak (4 hours after administration), aFXa levels increased significantly with an increase in enoxaparin dose, from 0.13 IU/ml at 40 mg, to 0.14 IU/ml at 50 mg, 0.27 IU/ml at 60 mg, and 0.29 IU/ml at 70 mg (P = 0.002). At 12 hours after administration, median aFXa levels were still within therapeutic range for those patients who received 60 mg (P = 0.02). CONCLUSIONS: Our study confirmed that a standard dose of 40 mg enoxaparin yielded subtherapeutic levels of aFXa in critically ill patients. Higher doses resulted in better peak aFXa levels, with a ceiling effect observed at 60 mg. The present study seems to suggest inadequate dosage as one of the possible mechanisms for the higher failure rate of enoxaparin in ICU patients. TRIAL REGISTRATION: ISRCTN03037804. PMID- 20298592 TI - Germ-line transmission of trisomy 21: Data from 80 families suggest an implication of grandmaternal age and a high frequency of female-specific trisomy rescue. AB - BACKGROUND: Trisomy of chromosome 21 (T21; Down syndrome, DS) is the most common aneuploidy in live births. Though its etiology has been intensively studied for a half of century, there are surprisingly many problems awaiting their elucidation. Some of the open questions are related directly to germ line mosaicism for T21, other problems include the prevalence of males with non-mosaic trisomy over females (skewed sex ratio, SR), the genetic predisposition to non-disjunction, etc. Studies in families of gonadal mosaicism (GM) carriers might help resolving some of these problems. RESULTS: 80 families of carriers of GM, in which the sex of the offspring had been specified, were identified in the literature and in logbooks of two local genetic units. Mothers in these families were relatively young: only 8% of mothers were 35 years old and older at the time of delivery of their first affected offspring while the proportion of grandmothers on the GM carrier's side aged 35 years old and older was significantly higher (39%). Postzygotic rescue of T21 due to error in the meiosis I had been proposed as a mechanism of parental GM formation in 78% of the families with known origin of the T21. For the other 22%, rescue of errors in the meiosis II or postzygotic mitotic non-disjunction was assumed. Mosaicism for T21 in successive generations was reported in at least 12 families. The proportion of mosaics among affected female offspring (14%) is significantly higher compared to that among affected male offspring (0%). Male preponderance (SR = 1.5) is found in non mosaic liveborn offspring with either maternally- or paternally transmitted T21. Among unaffected offspring of male carriers of GM there is a notable excess of females (SR = 0.27). CONCLUSION: Both direct (results of cytogenetic and molecular study of the origin of trisomic line) and indirect (advanced grandmaternal age on the side of GM carrier) evidences allow to assume that significant proportion of the mosaic parents had been conceived as trisomics. Female-specific trisomy rescue and genetic predisposition to postzygotic non-disjunction has been suggested as mechanisms of formation of both GM and somatic mosaicism. Typical male preponderance in affected non mosaic offspring with either maternally- or paternally transmitted trisomy 21, indicates than meiotic events are not responsible for the skewed sex ratio in DS. However a female excess among unaffected offspring of male carriers of GM might be the result of meiotic non homologous co-orientation of chromosomes 21 and X in spermatogenesis. PMID- 20298593 TI - Kruppel-like factor 5 is a crucial mediator of intestinal tumorigenesis in mice harboring combined ApcMin and KRASV12 mutations. AB - BACKGROUND: Both mutational inactivation of the adenomatous polyposis coli (APC) tumor suppressor gene and activation of the KRAS oncogene are implicated in the pathogenesis of colorectal cancer. Mice harboring a germline ApcMin mutation or intestine-specific expression of the KRASV12 gene have been developed. Both mouse strains develop spontaneous intestinal tumors, including adenoma and carcinoma, though at a different age. The zinc finger transcription factor Kruppel-like factor 5 (KLF5) has previously been shown to promote proliferation of intestinal epithelial cells and modulate intestinal tumorigenesis. Here we investigated the in vivo effect of Klf5 heterozygosity on the propensity of ApcMin/KRASV12 double transgenic mice to develop intestinal tumors. RESULTS: At 12 weeks of age, ApcMin/KRASV12 mice had three times as many intestinal tumors as ApcMin mice. This increase in tumor number was reduced by 92% in triple transgenic ApcMin/KRASV12/Klf5+/- mice. The reduction in tumor number in ApcMin/KRASV12/Klf5+/- mice was also statistically significant compared to ApcMin mice alone, with a 75% decrease. Compared with ApcMin/KRASV12, tumors from both ApcMin/KRASV12/Klf5+/- and ApcMin mice were smaller. In addition, tumors from ApcMin mice were more distally distributed in the intestine as contrasted by the more proximal distribution in ApcMin/KRASV12 and ApcMin/KRASV12/Klf5+/- mice. Klf5 levels in the normal-appearing intestinal mucosa were higher in both ApcMin and ApcMin/KRASV12 mice but were attenuated in ApcMin/KRASV12/Klf5+/- mice. The levels of beta-catenin, cyclin D1 and Ki-67 were also reduced in the normal appearing intestinal mucosa of ApcMin/KRASV12/Klf5+/- mice when compared to ApcMin/KRASV12 mice. Levels of pMek and pErk1/2 were elevated in the normal appearing mucosa of ApcMin/KRASV12 mice and modestly reduced in ApcMin/KRASV12/Klf5+/- mice. Tumor tissues displayed higher levels of both Klf5 and beta-catenin, irrespective of the mouse genotype from which tumors were derived. CONCLUSIONS: Results of the current study confirm the cumulative effect of Apc loss and oncogenic KRAS activation on intestinal tumorigenesis. The drastic reduction in tumor number and size due to Klf5 heterozygosity in ApcMin/KRASV12 mice indicate a critical function of KLF5 in modulating intestinal tumor initiation and progression. PMID- 20298594 TI - wDBTF: an integrated database resource for studying wheat transcription factor families. AB - BACKGROUND: Transcription factors (TFs) regulate gene expression by interacting with promoters of their target genes and are classified into families based on their DNA-binding domains. Genes coding for TFs have been identified in the sequences of model plant genomes. The rice (Oryza sativa spp. japonica) genome contains 2,384 TF gene models, which represent the mRNA transcript of a locus, classed into 63 families. RESULTS: We have created an extensive list of wheat (Triticum aestivum L) TF sequences based on sequence homology with rice TFs identified and classified in the Database of Rice Transcription Factors (DRTF). We have identified 7,112 wheat sequences (contigs and singletons) from a dataset of 1,033,960 expressed sequence tag and mRNA (ET) sequences available. This number is about three times the number of TFs in rice so proportionally is very similar if allowance is made for the hexaploidy of wheat. Of these sequences 3,820 encode gene products with a DNA-binding domain and thus were confirmed as potential regulators. These 3,820 sequences were classified into 40 families and 84 subfamilies and some members defined orphan families. The results were compiled in the Database of Wheat Transcription Factor (wDBTF), an inventory available on the web http://wwwappli.nantes.inra.fr:8180/wDBFT/. For each accession, a link to its library source and its Affymetrix identification number is provided. The positions of Pfam (protein family database) motifs were given when known. CONCLUSIONS: wDBTF collates 3,820 wheat TF sequences validated by the presence of a DNA-binding domain out of 7,112 potential TF sequences identified from publicly available gene expression data. We also incorporated in silico expression data on these TFs into the database. Thus this database provides a major resource for systematic studies of TF families and their expression in wheat as illustrated here in a study of DOF family members expressed during seed development. PMID- 20298595 TI - MPprimer: a program for reliable multiplex PCR primer design. AB - BACKGROUND: Multiplex PCR, defined as the simultaneous amplification of multiple regions of a DNA template or multiple DNA templates using more than one primer set (comprising a forward primer and a reverse primer) in one tube, has been widely used in diagnostic applications of clinical and environmental microbiology studies. However, primer design for multiplex PCR is still a challenging problem and several factors need to be considered. These problems include mis-priming due to nonspecific binding to non-target DNA templates, primer dimerization, and the inability to separate and purify DNA amplicons with similar electrophoretic mobility. RESULTS: A program named MPprimer was developed to help users for reliable multiplex PCR primer design. It employs the widely used primer design program Primer3 and the primer specificity evaluation program MFEprimer to design and evaluate the candidate primers based on genomic or transcript DNA database, followed by careful examination to avoid primer dimerization. The graph-expanding algorithm derived from the greedy algorithm was used to determine the optimal primer set combinations (PSCs) for multiplex PCR assay. In addition, MPprimer provides a virtual electrophotogram to help users choose the best PSC. The experimental validation from 2x to 5x plex PCR demonstrates the reliability of MPprimer. As another example, MPprimer is able to design the multiplex PCR primers for DMD (dystrophin gene which caused Duchenne Muscular Dystrophy), which has 79 exons, for 20x, 20x, 20x, 14x, and 5x plex PCR reactions in five tubes to detect underlying exon deletions. CONCLUSIONS: MPprimer is a valuable tool for designing specific, non-dimerizing primer set combinations with constrained amplicons size for multiplex PCR assays. PMID- 20298596 TI - Effectiveness of the 23-valent polysaccharide pneumococcal vaccine against invasive pneumococcal disease in people 60 years or older. AB - BACKGROUND: The 23-valent polysaccharide pneumococcal vaccine (PPV) is currently recommended in elderly and high-risk adults. However, its efficacy in preventing pneumococcal infections remains controversial. This study assessed the clinical effectiveness of vaccination against invasive pneumococcal disease (IPD) among people over 60 years. METHODS: Population-based case-control study that included 88 case patients over 60 years-old with a laboratory-confirmed IPD (bacteraemic pneumonia, meningitis or sepsis) and 176 outpatient control subjects who were matched by primary care centre, age, sex and risk stratum. Adjusted odds ratios (ORs) for vaccination were calculated using conditional logistic regression, controlling for underlying conditions. Vaccine effectiveness was estimated as (1 OR) x100. RESULTS: Pneumococcal vaccination rate was significantly lower in cases than in control subjects (38.6% vs 59.1%; p = 0.002). The adjusted vaccine effectiveness was 72% (OR: 0.28; 95% CI: 0.15-0.54) against all IPD and 77% (OR: 0.23; 95% CI: 0.08-0.60) against vaccine-type IPD. Vaccination was significantly effective against all IPD in both age groups: 60-79 years-old (OR 0.32; 95% CI: 0.14-0.74) and people 80 years or older (OR: 0.29; 95% CI: 0.09-0.91). Vaccination appears significantly effective as for high-risk immunocompetent subjects (OR: 0.29; 95% CI: 0.11-0.79) as well as for immunocompromised subjects (OR: 0.12; 95% CI: 0.03-0.53). CONCLUSION: These findings confirm the effectiveness of the 23-valent PPV against IPD, and they also support the benefit of vaccination in preventing invasive infections among high-risk and older people. PMID- 20298597 TI - Cytosolic group IVa phospholipase A2 mediates IL-8/CXCL8-induced transmigration of human polymorphonuclear leukocytes in vitro. AB - BACKGROUND: Cytosolic gIVaPLA2 is a critical enzyme in the generation of arachidonate metabolites and in induction of beta2-integrin adhesion in granulocytes. We hypothesized that gIVaPLA2 activation also is an essential downstream step for post adhesive migration of PMN in vitro. METHODS: Migration of PMNs caused by IL-8/CXCL8 was assessed using a transwell migration chamber. PMNs were pretreated with two structurally unrelated inhibitors of gIVaPLA2, arachidonyl trifluoromethylketone (TFMK) or pyrrophenone, prior to IL-8/CXCL8 exposure. The fraction of migrated PMNs present in the lower chamber was measured as total myeloperoxidase content. GIVaPLA2 enzyme activity was analyzed using [14C-PAPC] as specific substrate F-actin polymerization and cell structure were examined after rhodamine-phalloidin staining. RESULTS: IL-8/CXCL8-induced migration of PMNs was elicited in concentration- and time-dependent manner. Time related phosphorylation and translocation of cytosolic gIVaPLA2 to the nucleus was observed for PMNs stimulated with IL-8/CXCL8 in concentration sufficient to cause upstream phosphorylation of MAPKs (ERK-1/2 and p38) and Akt/PKB. Inhibition of gIVaPLA2 corresponded to the magnitude of blockade of PMN migration. Neither AA nor LTB4 secretion was elicited following IL-8/CXCL8 activation. In unstimulated PMNs, F-actin was located diffusely in the cytosol; however, a clear polarized morphology with F-actin-rich ruffles around the edges of the cell was observed after activation with IL-8/CXCL8. Inhibition of gIVaPLA2 blocked change in cell shape and migration caused by IL-8/CXCL8 but did not cause F-actin polymerization or translocation of cytosolic F-actin to inner leaflet of the PMN membrane. CONCLUSION: We demonstrate that IL-8/CXCL8 causes a) phosphorylation and translocation of cytosolic gIVaPLA2 to the nucleus, b) change in cell shape, c) polymerization of F-actin, and d) chemoattractant/migration of PMN in vitro. Inhibition of gIVaPLA2 blocks the deformability and subsequent migration of PMNs caused by IL-8/CXCL8. Our data suggest that activation of gIVaPLA2 is an essential step in PMN migration in vitro. PMID- 20298598 TI - Involvement of the genicular branches in cystic adventitial disease of the popliteal artery as a possible marker of unfavourable early clinical outcome: a case report. AB - INTRODUCTION: Cystic adventitial disease of the popliteal artery is a rare cause of non-atheromatous claudication. It usually requires surgery to improve the distance walked by patients. CASE PRESENTATION: We report the case of a 44-year old Caucasian man with unilateral symptomatic popliteal cysts extending to his genicular branches and associated with multilevel stenosis of his anterior tibial artery. A surgical evacuation of the cysts successfully restored his arterial patency and led to an objective haemodynamic improvement but was associated with early recurrence of symptoms. CONCLUSION: We suggest that the involvement of the genicular branches in cystic adventitial disease of the popliteal artery is a possible indicator of extensive adventitial degeneration and unfavourable clinical prognosis. PMID- 20298599 TI - Differential expression of genes in salivary glands of male Rhipicephalus (Boophilus)microplus in response to infection with Anaplasma marginale. AB - BACKGROUND: Bovine anaplasmosis, caused by the rickettsial tick-borne pathogen Anaplasma marginale (Rickettsiales: Anaplasmataceae), is vectored by Rhipicephalus (Boophilus)microplus in many tropical and subtropical regions of the world. A. marginale undergoes a complex developmental cycle in ticks which results in infection of salivary glands from where the pathogen is transmitted to cattle. In previous studies, we reported modification of gene expression in Dermacentor variabilis and cultured Ixodes scapularis tick cells in response to infection with A. marginale. In these studies, we extended these findings by use of a functional genomics approach to identify genes differentially expressed in R. microplus male salivary glands in response to A. marginale infection. Additionally, a R. microplus-derived cell line, BME26, was used for the first time to also study tick cell gene expression in response to A. marginale infection. RESULTS: Suppression subtractive hybridization libraries were constructed from infected and uninfected ticks and used to identify genes differentially expressed in male R. microplus salivary glands infected with A. marginale. A total of 279 ESTs were identified as candidate differentially expressed genes. Of these, five genes encoding for putative histamine-binding protein (22Hbp), von Willebrand factor (94Will), flagelliform silk protein (100Silk), Kunitz-like protease inhibitor precursor (108Kunz) and proline-rich protein BstNI subfamily 3 precursor (7BstNI3) were confirmed by real-time RT-PCR to be down-regulated in tick salivary glands infected with A. marginale. The impact of selected tick genes on A. marginale infections in tick salivary glands and BME26 cells was characterized by RNA interference. Silencing of the gene encoding for putative flagelliform silk protein (100Silk) resulted in reduced A. marginale infection in both tick salivary glands and cultured BME26 cells, while silencing of the gene encoding for subolesin (4D8) significantly reduced infection only in cultured BME26 cells. The knockdown of the gene encoding for putative metallothionein (93 Meth), significantly up-regulated in infected cultured BME26 cells, resulted in higher A. marginale infection levels in tick cells. CONCLUSIONS: Characterization of differential gene expression in salivary glands of R. microplus in response to A. marginale infection expands our understanding of the molecular mechanisms at the tick-pathogen interface. Functional studies suggested that differentially expressed genes encoding for subolesin, putative von Willebrand factor and flagelliform silk protein could play a role in A. marginale infection and multiplication in ticks. These tick genes found to be functionally relevant for tick-pathogen interactions will likely be candidates for development of vaccines designed for control of both ticks and tick-borne pathogens. PMID- 20298600 TI - Outcome and quality of life after aorto-bifemoral bypass surgery. AB - BACKGROUND: Aorto-bifemoral bypass (AFB) is commonly performed to treat aorto iliac disease and a durable long-term outcome is achieved. Most studies documenting beneficial outcomes after AFB have been limited to mortality and morbidity rates, costs and length of hospital stay (LOS). Few studies have examined the dependency of patients and how their perception of their own health changes after surgery. The aim of the present study was to evaluate outcome after AFB and to study its determinants. METHODS: This retrospective study was carried out in the multidisciplinary Post-Anaesthesia Care Unit (PACU) with five intensive care beds. Out of 1597 intensive care patients admitted to the PACU, 75 were submitted to infrarenal AFB and admitted to these intensive care unit (ICU) beds over 2 years. Preoperative characteristics and outcome were evaluated by comparing occlusive disease with aneurysmatic disease patients. Six months after discharge, the patients were contacted to complete a Short Form-36 questionnaire (SF-36) and to have their dependency in Activities of Daily Living (ADL) evaluated. Patient's characteristics and postoperative follow-up data were compared using Mann-Whitney U test, t test for independent groups, chi-square or Fisher's exact test. Patient preoperative characteristics were evaluated for associations with mortality using a multiple logistic regression analysis. RESULTS: The mortality rate was 12% at six months. Multivariate analysis identified congestive heart disease and APACHE II as independent determinants for mortality. Patients submitted to AFB for occlusive disease had worse SF-36 scores in role physical and general health perception. Patients submitted to AFB had worse SF-36 scores for all domains than a comparable urban population and had similar scores to other PACU patients. Sixty-six percent and 23% of patients were dependent in at least one activity in instrumental and personal ADL, respectively, but 64% reported having better general health. CONCLUSION: This study shows that congestive heart disease and APACHE II were risk factors for mortality after AFB surgery. Survivors who have undergone AFB perceive an improved quality of life although they are more dependent in ADL tasks and have worse scores in almost all SF-36 than the population to which they belong. PMID- 20298601 TI - Large-scale prediction of protein-protein interactions from structures. AB - BACKGROUND: The prediction of protein-protein interactions is an important step toward the elucidation of protein functions and the understanding of the molecular mechanisms inside the cell. While experimental methods for identifying these interactions remain costly and often noisy, the increasing quantity of solved 3D protein structures suggests that in silico methods to predict interactions between two protein structures will play an increasingly important role in screening candidate interacting pairs. Approaches using the knowledge of the structure are presumably more accurate than those based on sequence only. Approaches based on docking protein structures solve a variant of this problem, but these methods remain very computationally intensive and will not scale in the near future to the detection of interactions at the level of an interactome, involving millions of candidate pairs of proteins. RESULTS: Here, we describe a computational method to predict efficiently in silico whether two protein structures interact. This yes/no question is presumably easier to answer than the standard protein docking question, "How do these two protein structures interact?" Our approach is to discriminate between interacting and non interacting protein pairs using a statistical pattern recognition method known as a support vector machine (SVM). We demonstrate that our structure-based method performs well on this task and scales well to the size of an interactome. CONCLUSIONS: The use of structure information for the prediction of protein interaction yields significantly better performance than other sequence-based methods. Among structure-based classifiers, the SVM algorithm, combined with the metric learning pairwise kernel and the MAMMOTH kernel, performs best in our experiments. PMID- 20298602 TI - Left ventricular T2 distribution in Duchenne muscular dystrophy. AB - BACKGROUND: Although previous studies have helped define the natural history of Duchenne muscular dystrophy (DMD)-associated cardiomyopathy, the myocardial pathobiology associated with functional impairment in DMD is not yet known.The objective of this study was to assess the distribution of transverse relaxation time (T2) in the left ventricle (LV) of DMD patients, and to determine the association of myocardial T2 heterogeneity to the severity of cardiac dysfunction. DMD patients (n = 26) and normal control subjects (n = 13) were studied by cardiovascular magnetic resonance (CMR). DMD subject data was stratified based on subject age and LV ejection fraction (EF) into the following groups: A (<12 years old, n = 12); B (>or=12 years old, EF or=12 years old, EF = 55%, n = 6). Controls were also stratified by age into Groups N1 (<12 years, n = 6) and N2 (>12 years, n = 5). LV mid-slice circumferential myocardial strain (epsilon cc) was calculated using tagged CMR imaging. T2 maps of the LV were generated for all subjects using a black blood dual spin echo method at two echo times. The full width at half maximum (FWHM) was calculated from a histogram of LV T2 distribution constructed for each subject. RESULTS: In DMD subject groups, FWHM of the T2 histogram rose progressively with age and decreasing EF (Group A FWHM= 25.3 +/- 3.8 ms; Group B FWHM= 30.9 +/- 5.3 ms; Group C FWHM= 33.0 +/- 6.4 ms). Further, FWHM was significantly higher in those with reduced circumferential strain (|epsilon cc| 12% (Group A). Group A FWHM was not different from the two normal groups (N1 FWHM = 25.3 +/- 3.5 ms; N2 FWHM= 24.0 +/- 7.3 ms). CONCLUSION: Reduced EF and epsilon cc correlates well with increased T2 heterogeneity quantified by FWHM, indicating that subclinical functional impairments could be associated with pre-existing abnormalities in tissue structure in young DMD patients. PMID- 20298603 TI - Stoichiometry and intracellular fate of TRIM-containing TCR complexes. AB - BACKGROUND: Studying the stoichiometry and intracellular trafficking of the T cell antigen receptor (TCR) is pivotal in understanding its mechanisms of activation. The alphabetaTCR includes the antigen-binding TCRalphabeta heterodimer as well as the signal transducing CD3epsilongamma, CD3epsilondelta and zeta2 subunits. Although the TCR-interacting molecule (TRIM) is also part of the alphabetaTCR complex, it has not been included in most reports so far. RESULTS: We used the native antibody-based mobility shift (NAMOS) assay in a first dimension (1D) blue native (BN)-PAGE and a 2D BN-/BN-PAGE to demonstrate that the stoichiometry of the digitonin-solublized TRIM-containing alphabetaTCR is TCRalphabetaCD3epsilon2gammadeltazeta2TRIM2. Smaller alphabetaTCR complexes possess a TCRalphabeta CD3epsilon2gammadeltazeta2 stoichiometry. Complexes of these sizes were detected in T cell lines as well as in primary human and mouse T cells. Stimulating the alphabetaTCR with anti-CD3 antibodies, we demonstrate by confocal laser scanning microscopy that CD3epsilon colocalizes with zeta and both are degraded upon prolonged stimulation, possibly within the lysosomal compartment. In contrast, a substantial fraction of TRIM does not colocalize with zeta. Furthermore, TRIM neither moves to lysosomes nor is degraded. Immunoprecipitation studies and BN-PAGE indicate that TRIM also associates with the gammadeltaTCR. CONCLUSIONS: Small alphabetaTCR complexes have a TCRalphabeta CD3epsilon2gammadeltazeta2 stoichiometry; whereas those associated with one TRIM dimer are TCRalphabeta CD3epsilon2gammadeltazeta2TRIM2. TRIM is differentially processed compared to CD3 and zeta subunits after T cell activation and is not degraded. The gammadeltaTCR also associates with TRIM. PMID- 20298604 TI - Emotional reaction to diagnosis of infertility in Kuwait and successful clients' perception of nurses' role during treatment. AB - BACKGROUND: The unfulfilled desire of millions of infertile couples worldwide to have their own biological children results in emotional distress. This study evaluated the emotional reactions of couples attending a combined infertility clinic in Kuwait and successful clients' perception of nurses. METHODS: Quantitative and qualitative methods were used. The first phase was by structured interview using two standardized psychological scales: the 25-item Hopkins Symptom Checklist and Modified Fertility Adjustment Scale. Data were collected from 268 couples attending the combined infertility clinic, between October 2002 and September 2007. The second phase was a semi-structured interview of 10 clients who got pregnant following treatment. The interview explored their feelings and perception of the nurses' role. Interviews were transcribed verbatim and analyzed. RESULTS: The average duration of infertility was 4 years; 65.7% of the women and 76.1% of men suffered from primary infertility. Emotional reactions experienced were: anxiety in women (12.7%) and men (6%), depression in women (5.2%) and men (14.9%) and reduced libido in women (6.7%) and men (29.9%). Also in men, 14.9% experienced premature ejaculation, 5.2% weak ejaculation and 7.9% had impotence although 4.9% were transient. In the semi-structured interviews, the emotions expressed were similar and in addition to anger, feelings of devastation, powerlessness, sense of failure and frustration. In the survey, 12.7% of the men were found to show more anxiety than women (6%). Although all the 10 women interviewed confirmed they were anxious; only 4 of their partners were reported to be sad or anxious. Successful clients' perception of nurses' roles included nurses carrying out basic nursing procedures, communicating, educating about investigative and treatment procedures, providing emotional support by listening, encouraging, reassuring and being empathetic. CONCLUSIONS: This study illuminates the emotional reactions of infertile clients. Fertility nurses in Kuwait can provide emotional support through communication. The need for additional and continuous training for nurses employed in fertility settings in Kuwait is paramount. PMID- 20298605 TI - A cancer derived mutation in the retinoblastoma gene with a distinct defect for LXCXE dependent interactions. AB - BACKGROUND: The interaction between viral oncoproteins such as Simian virus 40 TAg, adenovirus E1A, and human papilloma virus E7, and the retinoblastoma protein (pRB) occurs through a well characterized peptide sequence, LXCXE, on the viral protein and a well conserved groove in the pocket domain of pRB. Cellular proteins, such as histone deacetylases, also use this mechanism to interact with the retinoblastoma protein to repress transcription at cell cycle regulated genes. For these reasons this region of the pRB pocket domain is thought to play a critical role in growth suppression. RESULTS: In this study, we identify and characterize a tumor derived allele of the retinoblastoma gene (RB1) that possesses a discrete defect in its ability to interact with LXCXE motif containing proteins that compromises proliferative control. To assess the frequency of similar mutations in the RB1 gene in human cancer, we screened blood and tumor samples for similar alleles. We screened almost 700 samples and did not detect additional mutations, indicating that this class of mutation is rare. CONCLUSIONS: Our work provides proof of principal that alleles encoding distinct, partial loss of function mutations in the retinoblastoma gene that specifically lose LXCXE dependent interactions, are found in human cancer. PMID- 20298606 TI - Limited educational attainment and radiographic and symptomatic knee osteoarthritis: a cross-sectional analysis using data from the Johnston County (North Carolina) Osteoarthritis Project. AB - INTRODUCTION: Applying a cross-sectional analysis to a sample of 2,627 African American and Caucasian adults aged > or = 45 years from the Johnston County Osteoarthritis Project, we studied the association between educational attainment and prevalence of radiographic knee osteoarthritis and symptomatic knee osteoarthritis. METHODS: Age- and race-adjusted associations between education and osteoarthritis outcomes were assessed by gender-stratified logistic regression models, with additional models adjusting for body mass index, knee injury, smoking, alcohol use, and occupational factors. RESULTS: In an analysis of all participants, low educational attainment (<12 years) was associated with higher prevalence of four knee osteoarthritis outcomes (unilateral and bilateral radiographic and symptomatic osteoarthritis). Women with low educational attainment had 50% higher odds of having radiographic knee osteoarthritis and 65% higher odds of symptomatic knee osteoarthritis compared with those with higher educational attainment (> or = 12 years), by using fully adjusted models. In the subset of postmenopausal women, these associations tended to be weaker but little affected by adjustment for hormone replacement therapy. Men with low educational attainment had 85% higher odds of having symptomatic knee osteoarthritis by using fully adjusted models, but the association with radiographic knee osteoarthritis was explained by age. CONCLUSIONS: After adjustment for known risk factors, educational attainment, as an indicator of socioeconomic status, is associated with symptomatic knee osteoarthritis in both men and women and with radiographic knee osteoarthritis in women. PMID- 20298607 TI - Zooming of states and parameters using a lumping approach including back translation. AB - BACKGROUND: Systems biology models tend to become large since biological systems often consist of complex networks of interacting components, and since the models usually are developed to reflect various mechanistic assumptions of those networks. Nevertheless, not all aspects of the model are equally interesting in a given setting, and normally there are parts that can be reduced without affecting the relevant model performance. There are many methods for model reduction, but few or none of them allow for a restoration of the details of the original model after the simplified model has been simulated. RESULTS: We present a reduction method that allows for such a back-translation from the reduced to the original model. The method is based on lumping of states, and includes a general and formal algorithm for both determining appropriate lumps, and for calculating the analytical back-translation formulas. The lumping makes use of efficient methods from graph-theory and -decomposition and is derived and exemplified on two published models for fluorescence emission in photosynthesis. The bigger of these models is reduced from 26 to 6 states, with a negligible deviation from the reduced model simulations, both when comparing simulations in the states of the reduced model and when comparing back-translated simulations in the states of the original model. The method is developed in a linear setting, but we exemplify how the same concepts and approaches can be applied to non-linear problems. Importantly, the method automatically provides a reduced model with back translations. Also, the method is implemented as a part of the systems biology toolbox for matlab, and the matlab scripts for the examples in this paper are available in the supplementary material. CONCLUSIONS: Our novel lumping methodology allows for both automatic reduction of states using lumping, and for analytical retrieval of the original states and parameters without performing a new simulation. The two models can thus be considered as two degrees of zooming of the same model. This is a conceptually new development of model reduction approaches, which we think will stimulate much further research and will prove to be very useful in future modelling projects. PMID- 20298608 TI - Optimization of preventive health care facility locations. AB - BACKGROUND: Preventive health care programs can save lives and contribute to a better quality of life by diagnosing serious medical conditions early. The Preventive Health Care Facility Location (PHCFL) problem is to identify optimal locations for preventive health care facilities so as to maximize participation. When identifying locations for preventive health care facilities, we need to consider the characteristics of the preventive health care services. First, people should have more flexibility to select service locations. Second, each preventive health care facility needs to have a minimum number of clients in order to retain accreditation. RESULTS: This paper presents a new methodology for solving the PHCFL problem. In order to capture the characteristics of preventive health care services, we define a new accessibility measurement that combines the two-step floating catchment area method, distance factor, and the Huff-based competitive model. We assume that the accessibility of preventive health care services is a major determinant for participation in the service. Based on the new accessibility measurement, the PHCFL problem is formalized as a bi-objective model based on efficiency and coverage. The bi-objective model is solved using the Interchange algorithm. In order to accelerate the solving process, we implement the Interchange algorithm by building two new data structures, which captures the spatial structure of the PHCFL problem. In addition, in order to measure the spatial barrier between clients and preventive health care facilities accurately and dynamically, this paper estimates travelling distance and travelling time by calling the Google Maps Application Programming Interface (API). CONCLUSIONS: Experiments based on a real application for the Alberta breast cancer screening program show that our work can increase the accessibility of breast cancer screening services in the province. PMID- 20298609 TI - Transmission ratio distortion results in asymmetric introgression in Louisiana Iris. AB - BACKGROUND: Linkage maps are useful tools for examining both the genetic architecture of quantitative traits and the evolution of reproductive incompatibilities. We describe the generation of two genetic maps using reciprocal interspecific backcross 1 (BC1) mapping populations from crosses between Iris brevicaulis and Iris fulva. These maps were constructed using expressed sequence tag (EST)- derived codominant microsatellite markers. Such a codominant marker system allowed for the ability to link the two reciprocal maps, and compare patterns of transmission ratio distortion observed between the two. RESULTS: Linkage mapping resulted in markers that coalesced into 21 linkage groups for each of the reciprocal backcross maps, presumably corresponding to the 21 haploid chromosomes of I. brevicaulis and I. fulva. The composite map was 1190.0-cM long, spanned 81% of the I. brevicaulis and I. fulva genomes, and had a mean density of 4.5 cM per locus. Transmission ratio distortion (TRD) was observed in 138 (48.5%) loci distributed in 19 of the 21 LGs in BCIB, BCIF, or both BC1 mapping populations. Of the distorted markers identified, I. fulva alleles were detected at consistently higher-than-expected frequencies in both mapping populations. CONCLUSIONS: The observation that I. fulva alleles are overrepresented in both mapping populations suggests that I. fulva alleles are favored to introgress into I. brevicaulis genetic backgrounds, while I. brevicaulis alleles would tend to be prevented from introgressing into I. fulva. These data are consistent with the previously observed patterns of introgression in natural hybrid zones, where I. fulva alleles have been consistently shown to introgress across species boundaries. PMID- 20298610 TI - Bilateral macular hole formation secondary to sclopetaria caused by shockwaves transmitted by a posterior vector: case report. AB - BACKGROUND: Sclopetaria is a rare ophthalmic finding in trauma CASE PRESENTATION: This is a report of a patient who developed macular holes from sclopetaria induced by indirect trauma. A 22-year-old male, suffered a gunshot wound that passed behind his eyes, resulting in bilateral macular hole formation CONCLUSION: To our knowledge, this is the first reported case in which trauma posterior to the globes caused bilateral macular hole formation. PMID- 20298611 TI - Measles outbreaks in displaced populations: a review of transmission, morbidity and mortality associated factors. AB - BACKGROUND: Measles is a highly contagious infectious disease with a significant public health impact especially among displaced populations due to their characteristic mass population displacement, high population density in camps and low measles vaccination coverage among children. While the fatality rate in stable populations is generally around 2%, evidence shows that it is usually high among populations displaced by disasters. In recent years, refugees and internally displaced persons have been increasing. Our study aims to define the epidemiological characteristics and risk factors associated with measles outbreaks in displaced populations. METHODS: We reviewed literature in the PubMed database, and selected articles for our analysis that quantitatively described measles outbreaks. RESULTS: A total of nine articles describing 11 measles outbreak studies were selected. The outbreaks occurred between 1979 and 2005 in Asia and Africa, mostly during post-conflict situations. Seven of eight outbreaks were associated with poor vaccination status (vaccination coverage; 17-57%), while one was predominantly due to one-dose vaccine coverage. The age of cases ranged from 1 month to 39 years. Children aged 6 months to 5 years were the most common target group for vaccination; however, 1622 cases (51.0% of the total cases) were older than 5 years of age. Higher case-fatality rates (>5%) were reported for five outbreaks. Consistent factors associated with measles transmission, morbidity and mortality were vaccination status, living conditions, movements of refugees, nutritional status and effectiveness of control measures including vaccination campaigns, surveillance and security situations in affected zones. No fatalities were reported in two outbreaks during which a combination of active and passive surveillance was employed. CONCLUSION: Measles patterns have varied over time among populations displaced by natural and man-made disasters. Appropriate risk assessment and surveillance strategies are essential approaches for reducing morbidity and mortality due to measles. Learning from past experiences of measles outbreaks in displaced populations is important for designing future strategies for measles control in such situations. PMID- 20298612 TI - Examination of equine glandular stomach lesions for bacteria, including Helicobacter spp by fluorescence in situ hybridisation. AB - BACKGROUND: The equine glandular stomach is commonly affected by erosion and ulceration. The aim of this study was to assess whether bacteria, including Helicobacter, could be involved in the aetiology of gastric glandular lesions seen in horses. RESULTS: Stomach lesions, as well as normal appearing mucosa were obtained from horses slaughtered for human consumption. All samples were tested for urease activity using the Pyloritek assay, while mucosal bacterial content was evaluated using Fluorescence In Situ Hybridisation. In selected sub samples, bacteria characterisation was pursued further by cloning and sequencing. Mucosal lesions were found in 36/63 stomachs and included hyperplastic rugae, polypoid structures and focal erosions. None of the samples were tested positive for urease activity or for FISH using the Helicobacter genus specific probe. In samples of lesions, as well as normal samples, clones with 99% similarities to Lactobacillus salivarius and Sarcina ventriculi were found. Escherichia like bacterium clones and Enterococcus clones were demonstrated in one focal erosion. Based on a phylogenetic tree these clones had 100% similarity to Escherichia fergusonii and Enterococcus faecium. The Enterococcus were found colonising the mucosal surface, while E. fergusonii organisms were also demonstrated intraepithelial. CONCLUSION: Gastric Helicobacter spp. could not be verified as being involved in lesions of the glandular stomach of the horse. Since E. fergusonii has been described as an emerging pathogen in both humans and animals, the finding of this bacterium in gastric erosion warrants further clarification to whether gastric infection with this type bacterium is important for horses. PMID- 20298613 TI - Factors associated with health-seeking behavior among migrant workers in Beijing, China. AB - BACKGROUND: Migrant workers are a unique phenomenon in the process of China's economic transformation. The household registration system classifies them as temporary residents in cities, putting them in a vulnerable state with an unfair share of urban infrastructure and social public welfare. The amount of pressure inflicted by migrant workers in Beijing, as one of the major migration destinations, is currently at a threshold. This study was designed to assess the factors associated with health-seeking behavior and to explore feasible solutions to the obstacles migrant workers in China faced with when accessing health-care. METHODS: A sample of 2,478 migrant workers in Beijing was chosen by the multi stage stratified cluster sampling method. A structured questionnaire survey was conducted via face-to-face interviews between investigators and subjects. The multilevel methodology (MLM) was used to demonstrate the independent effects of the explanatory variables on health seeking behavior in migrant workers. RESULTS: The medical visitation rate of migrant workers within the past two weeks was 4.8%, which only accounted for 36.4% of those who were ill. Nearly one-third of the migrant workers chose self-medication (33.3%) or no measures (30.3%) while ill within the past two weeks. 19.7% of the sick migrants who should have been hospitalized failed to receive medical treatment within the past year. According to self-reported reasons, the high cost of health service was a significant obstacle to health-care access for 40.5% of the migrant workers who became sick. However, 94.0% of the migrant workers didn't have any insurance coverage in Beijing. The multilevel model analysis indicates that health-seeking behavior among migrants is significantly associated with their insurance coverage. Meanwhile, such factors as household monthly income per capita and working hours per day also affect the medical visitation rate of the migrant workers in Beijing. CONCLUSION: This study assesses the influence of socio-demographic characteristics on the migrant workers' decision to seek health care services when they fall ill, and it also indicates that the current health service system discourages migrant workers from seeking appropriate care of good quality. Relevant policies of public medical insurance and assistance program should be vigorously implemented for providing affordable health care services to the migrants. Feasible measures need to be taken to reduce the health risks associated with current hygiene practices and equity should be assured in access to health care services among migrant workers. PMID- 20298614 TI - Effect of smoking on lung function, respiratory symptoms and respiratory diseases amongst HIV-positive subjects: a cross-sectional study. AB - BACKGROUND: Smoking prevalence in human immunodeficiency virus (HIV) positive subjects is about three times of that in the general population. However, whether the extremely high smoking prevalence in HIV-positive subjects affects their lung function is unclear, particularly whether smoking decreases lung function more in HIV-positive subjects, compared to the general population. We conducted this study to determine the association between smoking and lung function, respiratory symptoms and diseases amongst HIV-positive subjects. RESULTS: Of 120 enrolled HIV positive subjects, 119 had an acceptable spirogram. Ninety-four (79%) subjects were men, and 96 (81%) were white. Mean (standard deviation [SD]) age was 43.4 (8.4) years. Mean (SD) of forced expiratory volume in one second (FEV1) percent of age, gender, race and height predicted value (%FEV1) was 93.1% (15.7%). Seventy-five (63%) subjects had smoked 24.0 (18.0) pack-years. For every ten pack years of smoking increment, %FEV1 decreased by 2.1% (95% confidence interval [CI]: -3.6%, -0.6%), after controlling for gender, race and restrictive lung function (R2 = 0.210). The loss of %FEV1 in our subjects was comparable to the general population. Compared to non-smokers, current smokers had higher odds of cough, sputum or breathlessness, after adjusting for highly active anti retroviral therapy (HAART) use, odds ratio OR = 4.9 (95% CI: 2.0, 11.8). However respiratory symptom presence was similar between non-smokers and former smokers, OR = 1.0 (95% CI: 0.3, 2.8). All four cases of COPD (chronic obstructive pulmonary disease) had smoked. Four of ten cases of restrictive lung disease had smoked (p = 0.170), and three of five asthmatic subjects had smoked (p = 1.000). CONCLUSIONS: Cumulative cigarette consumption was associated with worse lung function; however the loss of %FEV1 did not accelerate in HIV-positive population compared to the general population. Current smokers had higher odds of respiratory symptoms than non-smokers, while former smokers had the same odds of respiratory symptoms as non-smokers. Cigarette consumption was likely associated with more COPD cases in HIV-positive population; however more participants and longer follow up would be needed to estimate the effect of smoking on COPD development. Effective smoking cessation strategies are required for HIV-positive subjects. PMID- 20298616 TI - Association of depression with newly diagnosed type 2 diabetes among adults aged between 25 to 60 years in Karachi, Pakistan. AB - BACKGROUND: The combination of depression with type 2 diabetes is a public health problem. If diabetes is managed in its initial phase, the morbidity and mortality due to this combination may be prevented at an early stage. Therefore, we aimed to determine the association of depression with newly diagnosed type 2 diabetes among adults aged between 25 to 60 years in Karachi, Pakistan. METHODS: From July 2006 to September 2007, a matched case control study (n = 592) was conducted in Civil Hospital, Karachi. Incident cases of type 2 diabetes (n = 296) diagnosed within one month were recruited from diabetic Out Patient Department (OPD) of Civil Hospital, Karachi. They were matched on age and sex with controls (n = 296), who were attendants sitting in the medical out patient department of the same hospital, recruited on the basis of absence of classical symptoms of polyuria and polydipsia along with random blood glucose level of <200 mg/dl measured by a glucometer. Depression was identified by the Siddiqui Shah Depression Scale. Conditional logistic regression was applied to examine the association of depression and other independent variables with newly diagnosed type 2 diabetes at 95% C.I. and P < 0.05. RESULTS: The study comprised of 592 subjects with 432(73%) males and 160(27%) females. Depression was significantly associated with newly diagnosed type 2 diabetes having mild level (mOR: 3.86; 95%CI: 2.22,6.71) and moderate to severe level (mOR: 3.41; 95%CI: 2.07,5.61). History of (h/o) gestational diabetes (mOR: 2.83; 95%CI: 1.05,7.64), family h/o diabetes (mOR: 1.59; 95%CI: 1.04,2.43), nuclear family (mOR: 1.75; 95%CI: 1.14,2.69), BMI (mOR: 1.62; 95%CI: 1.01,2.60 for obese and mOR: 2.12; 95%CI: 1.19,3.79 for overweight vs healthy to underweight) were also significantly associated with outcome, adjusting for age, sex, marital status, h/o smoking and h/o high BP. CONCLUSIONS: Diabetics should be screened simultaneously for depression and concomitant preventive strategies for gestational diabetes, nuclear family and high BMI should also be used to prevent mortality/morbidity among patients between 25 to 60 years of age. PMID- 20298617 TI - Small ruminant feed systems: perceptions and practices in the transitional zone of Ghana. AB - BACKGROUND: Adequate feeding is essential to realizing the potential of small ruminants to alleviate poverty among smallholder farmers. This study was conducted in two villages in the Ejura-Sekyedumase District of Ghana and was motivated by farmers' non-adoption of modern feed technologies, but more importantly by the need to understand the small ruminant feed system considering farmers' different socio-economic backgrounds and how these relate to small ruminant performance. In this study, the feed system was defined as the type, source and seasonality of feeds and how small ruminants access them. METHODS: Qualitative and quantitative methods were used to allow for triangulation. Data were collected in seven stages comprising key informant interviews, a census, a cultural domain study, botanical specimen collection and identification, focus group discussions, a household survey, and a small ruminant performance study. RESULTS: Farmers listed 175 items that are used as small ruminant feed and salience indexes were calculated. There was high consensus about the domain of small ruminant feeds, with 15 items comprising the consensus model. Respondent agreement scores correlated positively with age and negatively with list length. Respondents from matrilineal lineages had higher agreement scores than those from patrilineal lineages. Natural pasture and wild browse scored high in pair wise ranking by village and sex groups. Of the 33 feeds that farmers fed to goats, maize grains, cassava peels and Margaritaria discoidea were the most salient. Six major feed system groups based on access were identified at household level, which regrouped into three at village level based on feed type and source. Patrilineal households were more likely to tether their livestock. Significant differences were found between some socio-economic groups for pre-weaning average daily gain (ADG) of kids, but not for prolificacy of does. CONCLUSIONS: The need for nutritive and agronomic investigations into major feeds, the creation of non cropping zones around village fringes and studies on labour demands of different feed systems are proposed. The insight gained in this study on farmers' perceptions and practices relating to small ruminant feeds could guide in the selection and introduction of feed innovations that fit into current feed systems to enhance adoption. PMID- 20298615 TI - Production of recombinant proteins in E. coli by the heat inducible expression system based on the phage lambda pL and/or pR promoters. AB - The temperature inducible expression system, based on the pL and/or pR phage lambda promoters regulated by the thermolabile cI857 repressor has been widely use to produce recombinant proteins in prokaryotic cells. In this expression system, induction of heterologous protein is achieved by increasing the culture temperature, generally above 37 degrees C. Concomitant to the overexpression of heterologous protein, the increase in temperature also causes a variety of complex stress responses. Many studies have reported the use of such temperature inducible expression system, however only few discuss the simultaneous stress effects caused by recombinant protein production and the up-shift in temperature. Understanding the integral effect of such responses should be useful to develop improved strategies for high yield protein production and recovery. Here, we describe the current status of the heat inducible expression system based on the pL and/or pR lambda phage promoters, focusing on recent developments on expression vehicles, the stress responses at the molecular and physiological level that occur after heat induction, and bioprocessing factors that affect protein overexpression, including culture operation variables and induction strategies. PMID- 20298618 TI - Effects of automated alerts on unnecessarily repeated serology tests in a cardiovascular surgery department: a time series analysis. AB - BACKGROUND: Laboratory testing is frequently unnecessary, particularly repetitive testing. Among the interventions proposed to reduce unnecessary testing, Computerized Decision Support Systems (CDSS) have been shown to be effective, but their impact depends on their technical characteristics. The objective of the study was to evaluate the impact of a Serology-CDSS providing point of care reminders of previous existing serology results, embedded in a Computerized Physician Order Entry at a university teaching hospital in Paris, France. METHODS: A CDSS was implemented in the Cardiovascular Surgery department of the hospital in order to decrease inappropriate repetitions of viral serology tests (HBV).A time series analysis was performed to assess the impact of the alert on physicians' practices. The study took place between January 2004 and December 2007. The primary outcome was the proportion of unnecessarily repeated HBs antigen tests over the periods of the study. A test was considered unnecessary when it was ordered within 90 days after a previous test for the same patient. A secondary outcome was the proportion of potentially unnecessary HBs antigen test orders cancelled after an alert display. RESULTS: In the pre-intervention period, 3,480 viral serology tests were ordered, of which 538 (15.5%) were unnecessarily repeated. During the intervention period, of the 2,095 HBs antigen tests performed, 330 unnecessary repetitions (15.8%) were observed. Before the intervention, the mean proportion of unnecessarily repeated HBs antigen tests increased by 0.4% per month (absolute increase, 95% CI 0.2% to 0.6%, p < 0.001). After the intervention, a significant trend change occurred, with a monthly difference estimated at -0.4% (95% CI -0.7% to -0.1%, p = 0.02) resulting in a stable proportion of unnecessarily repeated HBs antigen tests. A total of 380 unnecessary tests were ordered among 500 alerts displayed (compliance rate 24%). CONCLUSIONS: The proportion of unnecessarily repeated tests immediately dropped after CDSS implementation and remained stable, contrasting with the significant continuous increase observed before. The compliance rate confirmed the effect of the alerts. It is necessary to continue experimentation with dedicated systems in order to improve understanding of the diversity of CDSS and their impact on clinical practice. PMID- 20298619 TI - Diversity in anopheline larval habitats and adult composition during the dry and wet seasons in Ouagadougou (Burkina Faso). AB - BACKGROUND: Several cases of malaria are frequently recorded during the dry period in Ouagadougou town (Burkina Faso). This has led to the design of a series of studies focusing on both parasitological and entomological investigations intended to provide relevant health data on the risk of local malaria transmission according to the way of urbanisation. METHODS: A cross-sectional entomological survey was carried out in various districts of Ouagadougou in April and October 2006. Adult malaria vectors were collected using CDC traps and indoor insecticide spraying performed in four houses during four consecutive days/nights. Intensive larval sampling was also done in available water ponds throughout the study sites. RESULTS: In April, the anopheline breeding sites consisted only of semi-permanent or permanent swamps located mainly in the two peripheral districts. Despite the presence of anopheline larvae in these breeding sites, less than five Anopheles gambiae s.l. adults were caught by CDC traps and indoor insecticide spraying. In October, additionally to the permanent breeding sites reported in April, some rainfall swamps were also found positive to anophelines. The number of adults' mosquitoes was higher than that collected in April (2 vs 159 in October). Out of 115 larvae of An. gambiae s.l. analysed by PCR in April, 59.1% (68/115) were identified as Anopheles arabiensis, 39.1% (45/115) as An. gambiae M while the S form represented less than 2%. Overall 120 larvae and 86 females were identified by PCR in October as An. gambiae M form (51%) and An. arabiensis (42.2%). The S form represented only 6.8%. The global sporozoite rate recorded was high (6.8%) and did not differ between the districts except in the central district where no positive mosquito was detected. CONCLUSION: Although only few adults' mosquitoes were actively caught during the driest month, malaria vectors persisted all year long that increases the risk of urban malaria transmission. The distribution of breeding sites and especially the occurrence of malaria vectors were more abundant in the periphery, which is more like that of a rural settlement. The evolution of malaria prevalence and the factors sustaining the risk of transmission in Ouagadougou as well in many African cities during the dry season are discussed. PMID- 20298620 TI - [Medical problems of musicians]. AB - Most individuals enjoy making music, but pleasure may be diminished by physical complaints. The most common complaints in musicians include injuries of the upper part of the body including the shoulder and spine, skin disorders and hearing problems. Injuries are not so much related to the extent of rehearsing and playing but are mostly the result of a wrong position and misuse of the instrument. Adequate preparation before playing and professional coaching to avoid injuries or to detect problems at an early stage are exceptions rather than the rule. Because of the large number of amateur and professional musicians in the Netherlands, music medicine deserves a more prominent role. PMID- 20298622 TI - [Advice on guidelines: planning for guideline development in the Netherlands]. AB - There is a lack of shared responsibility and national steering in guideline development. The 'Regieraad' (advisory board on guideline development, established by the Dutch Health Secretary) hopes to facilitate the coordination of guideline development. Therefore, the board developed a shortlist of the 100 most important diseases and 25 important care processes, based on several accepted criteria. An inventory of already available guidelines and other instruments for quality improvement was also made. The board thinks that guidelines should become more uniform to improve accessibility and usefulness for daily practice. The board encourages the availability of guidelines for the most important topics. With the information available a long-term policy for guideline development and maintenance can be determined. PMID- 20298623 TI - [Dutch parliament legitimizes harmful quackery]. AB - The Dutch parliament has recently accepted a tax law in which certain groups of alternative therapists can be exempt from VAT. To be eligible for this VAT exemption, the disciplines to which the therapists belong have to meet certain training requirements. In this article it is contended, in agreement with the Royal College of Physicians in the UK, that statutory regulation is inappropriate for disciplines whose therapies are neither of proved benefit nor appropriately tested. It legitimizes harmful therapies. This is illustrated by two serious accidents, previously described in this journal, caused by a chiropractor and a craniosacral therapist. PMID- 20298624 TI - [Colonic obstruction due to volvulus of the sigmoid colon or caecum]. AB - 3 patients, 2 women aged 41 and 47 and one man aged 75 years, presented with abdominal pain and distension. In 2 patients the diagnosis 'sigmoid volvulus' was reached following plain abdominal X-ray. Both patients underwent sigmoidal resection with primary anastomosis after endoscopic deflation. The third patient proved to have a caecal volvulus on emergency laparotomy and underwent ileocaecal resection. In 2/3 of the cases diagnosis can be made by history, physical examination and conventional X-ray. Delay in the diagnosis increases the risk of peritonitis and death due to ischaemia and perforation of the colon. In the absence of peritoneal tenderness, signs of ischaemia or sepsis, the initial treatment consists of endoscopic deflation, which is successful in 68-78% of cases. Resection of the sigmoid colon is recommended a few days after endoscopic decompression in order to prevent recurrence. Caecal volvulus is not suitable for treatment with endoscopic deflation and should be treated with ileocaecal resection. PMID- 20298625 TI - [New blood glucose-lowering drugs in type 2 diabetes: a review of the literature]. AB - OBJECTIVE: To describe the efficacy and safety of the glucagon-like peptide 1 (GLP-1) analogues exenatide and liraglutide, and the dipeptidyl peptidase-4 (DPP 4) inhibitors vildagliptin and sitagliptin, registered in the Netherlands for treatment of type 2 diabetes mellitus (DM2). DESIGN: Literature study. METHOD: The Medline database was searched up to and including August 2009 for systematic reviews and randomised trials with a minimum duration of 12 weeks in patients with DM2. Two authors independently selected the studies based on the title, abstract and, if necessary, the full text. RESULTS: In addition to 1 systematic review on GLP-1 analogues and 1 review on DPP-4 inhibitors, 10 studies on DPP-4 inhibitors and 16 studies on GLP-1 analogues were included. According to these studies, the DPP-4 inhibitors sitagliptin and vildagliptin gave a mean HbA1c reduction of 0.7% and 0.6% respectively. GLP-1 analogues led to a mean HbA1c reduction of 1%, which is comparable to insulin therapy. Sitagliptin was associated with a slight increase in the number of upper respiratory tract infections. In a large number of patients, GLP-1 analogues were associated with gastrointestinal complaints. DPP-4 inhibitors were associated with a small weight gain, compared with weight loss in patients treated with GLP-1 analogues. Data on microvascular and macrovascular complications, as well as data on mortality, are not yet available in either group. CONCLUSION: GLP-1 analogues regulate blood glucose levels as effectively as the current glucose-lowering agents; DPP-4 inhibitors are less effective. GLP-1 analogues lead to a clear weight reduction while DPP-4 inhibitors cause slight weight gain. Data on efficacy and safety in the longer term are not yet available. PMID- 20298626 TI - [Subcutaneous emphysema as the initial symptom of perforated diverticulitis]. AB - A 76-year-old woman with no medical history apart from hypertension was admitted to the department of Internal Medicine with rectal bleeding. A few days later she complained of severe pain in her left leg. On physical examination the leg was swollen, shiny and extremely painful to the touch. Later she developed subcutaneous emphysema of the upper leg. A CT-scan revealed perforated sigmoid diverticulitis and extensive subcutaneous and intramuscular emphysema. During surgery, a double-barrelled colostomy was raised on the transverse colon. All subcutaneous areas with emphysema were drained. During a second operation, a Hartmann resection was performed, with a distal mucous fistula on the descending colon. A few days later she died as a result of septicaemia. Subcutaneous emphysema is a rare complication of perforated diverticulitis. A lack of prospective studies on diverticulitis hampers a rational approach to this common condition in daily practice. PMID- 20298627 TI - [A dead man with a light reddish skin]. AB - A 40-year-old man was found dead in his bathroom with a light reddish skin. The cause of death was asphyxia due to CO-intoxication. PMID- 20298628 TI - [Presentation of illness in the elderly: a simple explanation for a complex problem]. AB - Illness presentation in the elderly is often complex and atypical. This may cause negative health outcomes. In the standard medical model of diagnosis, there is a 1:1 correspondence between clinical signs and symptoms and a pathological disease process. This model can be only applied to some presentations of illness in the elderly. For this reason Linda Fried, 'grande dame' of geriatric medicine in the United States, developed four complementary generic diagnostic models, taking into account social and functional aspects as well as clinical symptoms. Here we present these models for a broader audience, since not only geriatricians but all physicians are being confronted with a growing population of older patients. PMID- 20298629 TI - [Primary management and treatment of paediatric septic shock]. AB - Paediatric shock is common. Hypovolaemic and septic shock are the main forms. Early and rapid results-oriented therapy of paediatric septic shock has a favourable effect on survival. There is an international guideline for the primary management of paediatric shock during the first hour after presentation of the patient. The goal of treatment is to prevent oxygen debt and consequently organ failure. The main symptoms of paediatric shock are tachycardia and reduced consciousness. In a child in shock, the clinical picture should be recognized within 15 minutes and an attempt should be made to reverse the situation by rapid fluid infusion. If the shock persists after 15 minutes, vasoactive medication should be given and the child should be transferred to a local paediatric intensive care unit. Intubation and mechanical ventilation are then also required. PMID- 20298630 TI - [Gut instinct among GPs] PMID- 20298631 TI - [The role of gut instinct is an important subject]. AB - The role of gut instinct in general practice is an important topic. The reliance on gut instinct by experienced doctors is thought to be a form of intuitive decision-making which fits in with System 1 processes in the dual process model in higher cognition. Special mention is made of the theories on intuitive decision-making by the famous Dutch psychologist De Groot, who, when investigating thought processes of chess masters more than half a century ago, developed a fundamental theory on intuitive heuristics. Further studies on the determinants and conditions under which heuristics, such as the reliance on gut instinct, are applied in clinical practice are very welcome. PMID- 20298632 TI - [A progressive vomiting pre-schooler]. AB - A 4-year-old boy with persistent vomiting had a peptic stenosis of the oesophagus. PMID- 20298633 TI - [A women with a lumpy calf]. AB - A 24-year-old woman had big neurofibromas on her left leg caused by type 1 neurofibromatosis. Four kilograms of tissue were excised. PMID- 20298634 TI - [Reversible thrombocytopenia and polyneuropathy: the pleiotropic aspects of hypothyroidism]. AB - Although the relationship between hyperthyroidism and thrombocytopenia is well documented, the relationship between hypothyroidism and thrombocytopenia is less well known. We describe a 69-year-old man with severe hypothyroidism, mild thrombocytopenia and sensorimotor axonal polyneuropathy. After thyroid hormone replacement therapy, he became euthyroid and his platelet count normalized over a period of three months. The thrombocytopenia may have been due to an immunomodulatory effect of thyroid-stimulating hormone (TSH). His neurological complaints disappeared and even though electromyography still showed signs of axonal polyneuropathy, nerve conduction velocities normalized and he had signs of re-innervation. Our case clearly demonstrates that hypothyroidism is a heterogeneous disease. As symptoms may be reversible with thyroid hormone replacement therapy, it should not be overlooked. PMID- 20298635 TI - [Cold ischaemia time and outcome of renal transplantation]. AB - OBJECTIVE: To determine the effect of cold ischaemia time (CIT) on the outcome of cadaveric renal transplantation in the Netherlands. DESIGN: Retrospective, comparative. METHODS: We studied data from the Netherlands organ transplant registry of cadaveric renal transplants from 1990-2007. RESULTS: 6322 cadaveric renal transplant recipients were studied, of whom 5306 were from heart-beating donors (HBD) and 1016 from non-heart-beating donors (NHBD). The mean CIT was 24.0 h in the HBD group and 21.6 h in the NHBD group. The rate of delayed graft function (DGF) was 12.3% in the HBD group and 50.4% in the NHBD group. Multivariate analysis showed that prolonged CIT was an independent risk factor for graft failure. Prolonged CIT was also associated with the more frequent occurrence of DGF and primary non-function (PNF). Recipients of renal allografts from HBD with CIT .05 for both). In summary, distractors that were similar to targets elicited significant interference effects circumscribed to object selection. PMID- 20298639 TI - A test of the cerebellar hypothesis of dyslexia in adequate and inadequate responders to reading intervention. AB - The cerebellar hypothesis of dyslexia posits that cerebellar deficits are associated with reading disabilities and may explain why some individuals with reading disabilities fail to respond to reading interventions. We tested these hypotheses in a sample of children who participated in a grade 1 reading intervention study (n = 174) and a group of typically achieving children (n = 62). At posttest, children were classified as adequately responding to the intervention (n = 82), inadequately responding with decoding and fluency deficits (n = 36), or inadequately responding with only fluency deficits (n = 56). Based on the Bead Threading and Postural Stability subtests from the Dyslexia Screening Test-Junior, we found little evidence that assessments of cerebellar functions were associated with academic performance or responder status. In addition, we did not find evidence supporting the hypothesis that cerebellar deficits are more prominent for poor readers with "specific" reading disabilities (i.e., with discrepancies relative to IQ) than for poor readers with reading scores consistent with IQ. In contrast, measures of phonological awareness, rapid naming, and vocabulary were strongly associated with responder status and academic outcomes. These results add to accumulating evidence that fails to associate cerebellar functions with reading difficulties. PMID- 20298640 TI - Exploring the recollective experience during autobiographical memory retrieval in amnestic mild cognitive impairment. AB - Autonoetic consciousness refers to the ability to mentally transport oneself back in subjective time to relive elements of, or all, of a past event, and is compromised in the early stages of Alzheimer's disease (AD). Here, we investigate autobiographical memory (ABM) and the recollective experience in amnestic mild cognitive impairment (aMCI). aMCI participants exhibited significant deficits compared with healthy elderly controls for both personal semantic and event detail components of ABM. These decrements were evident across all life epochs for episodic recall. Recall of an event that occurred 1 week previously, was tested in the same spatiotemporal context, and provided the greatest group dissociation, with elderly controls benefitting from a context-dependent memory effect. This reinstantiation of context did not ameliorate the anterograde deficits in the aMCI cohort, nor did it facilitate the mental reliving of these memories for either participant group. Whereas reliving judgments were comparable in both groups, aMCI participants exhibited a compromised capacity to generate vivid, self-referential visual imagery and to re-experience the original emotion of events. These contextual and experiential deficits extended beyond recently encountered events into remote epochs, and suggest a greater level of ABM impairment in aMCI than previously assumed. PMID- 20298641 TI - Neuropsychological deficits associated with Complex Regional Pain Syndrome. AB - We sought to elucidate the existence of neuropsychological subtypes in Complex Regional Pain Syndrome (CRPS). One hundred thirty seven patients with CRPS were administered tests that assess executive control, naming/lexical retrieval, and declarative memory. A 2-step cluster analysis that does not require any a priori specification regarding the number of clusters, classified patients into three groups. Group 1 obtained scores that were in the average range on all tests (n = 48; normal CRSP group). Group 2 (n = 58; dysexecutive CRSP group) presented with mild impairment or statistically low average test performance on working memory/verbal fluency tests. Group 3 (n = 31; global CRSP group) produced scores in the statistically low average/borderline range on all tests with particularly reduced scores on naming/declarative memory tests. Between-group analyses found that the CRPS group 1 obtained higher scores than CRPS groups 2 and 3 on all tests. However, groups 2 and 3 were equally impaired on executive tests. CRPS group 3 was impaired on tests of naming/memory tests compared to the other groups. Significant neuropsychological deficits are present in 65% of patients, with many patients presenting with elements of a dysexecutive syndrome and some patients presenting with global cognitive impairment. PMID- 20298642 TI - Heart rate and blood pressure effects during caloric vestibular testing. AB - OBJECTIVES: To determine whether the caloric vestibular test causes significant changes in heart rate and mean arterial blood pressure. MATERIALS AND METHODS: Changes in heart rate and mean arterial blood pressure before and after caloric irrigation were compared with the degree of nystagmus (as measured by maximum slow phase velocity) and the patient's subjective dizziness (scored from 0 to 10). A cardiologist reviewed each patient's heart rate and mean arterial blood pressure changes. Patients' anxiety levels were also assessed. RESULTS: Eighteen patients were recruited. There were no adverse events in any patient. There were no overall significant differences between the heart rate and mean arterial pressure before and after each irrigation. There was a significant correlation between the maximum slow phase velocity and patients' subjective dizziness scores. CONCLUSION: Heart rate and mean arterial blood pressure are not significantly influenced by the caloric vestibular test. This preliminary study will enable patients with stable cardiovascular disease to be recruited for further risk determination. PMID- 20298643 TI - Superior sagittal sinus thrombosis complicating neck dissection. AB - OBJECTIVE: To report a superior sagittal sinus thrombosis occurring as a rare complication of neck dissection, and to present a review of published literature. CASE REPORT: A 42-year-old man underwent an elective neck dissection for a tumour stage 2, node stage 2b, tonsillar squamous cell carcinoma, prior to chemoradiotherapy. During surgery, the right internal jugular vein was sacrificed as part of the resection, as tumour was adherent to it. Two weeks after surgery, the patient was readmitted with seizures. Subsequent computed tomography and magnetic resonance venography confirmed a superior sagittal sinus thrombosis. The patient was subsequently anticoagulated and underwent radiotherapy without further complication. A review of pre-operative imaging indicated a dominant internal jugular vein, ligation of which may have been a factor in the subsequent sagittal sinus thrombosis. CONCLUSION: Superior sagittal sinus thrombosis following neck dissection is a rare occurrence, with little reported in the literature. Dominant internal jugular vein anatomy may be evident on pre operative imaging. An awareness of this complication may be helpful to surgeons contemplating sacrifice of the internal jugular vein. PMID- 20298644 TI - Techniques for early diagnosis and management of cervicofacial necrotising fasciitis. AB - BACKGROUND: Cervicofacial necrotising fasciitis carries high rates of morbidity and mortality, and is not often initially suspected due to its rarity and misleadingly innocuous presentation. We propose an algorithm for the timely diagnosis and management of cervicofacial necrotising fasciitis. METHODS: Retrospective review of seven patients ultimately diagnosed with cervicofacial necrotising fasciitis. RESULTS: In these seven patients, common presenting symptoms included sore throat, fever and neck pain. On initial examination and imaging, only three had obvious findings. One patient's diagnosis was facilitated via a bedside cut-down procedure. Six patients underwent surgical debridement. Four required tracheotomy, and five wounds closed via secondary intention. There were two deaths. CONCLUSION: The severity of cervical necrotising fasciitis and its rapid spread necessitate early diagnosis and timely surgical management. The presentation often appears benign. A high index of clinical suspicion should be maintained in cases of neck cellulitis with nonspecific clinical findings, especially in diabetic or otherwise immunocompromised patients. A normal computed tomography scan does not rule out necrotising fasciitis. A cut-down procedure may be critical to early diagnosis in some cases. PMID- 20298645 TI - The a(d) coefficient as a descriptive measure of the within-group agreement of ratings. AB - The a(d) coefficient was developed to measure the within-group agreement of ratings. The underlying theory as well as the construction of the coefficient are explained. The a(d) coefficient ranges from 0 to 1, regardless of the number of scale points, raters, or items. With some limitations the measure of the within group agreement of different groups and groups from different studies is directly comparable. For statistical significance testing, the binomial distribution is introduced as a model of the ratings' random distribution given the true score of a group construct. This method enables a decision about essential agreement and not only about a significant difference from 0 or a chosen critical value. The a(d) coefficient identifies a single true score within a group. It is not provided for multiple true score settings. The comparison of the a(d) coefficient with other agreement indices shows that the new coefficient is in line with their outcomes, but does not result in infinite or inappropriate values. PMID- 20298646 TI - Local anesthesia during dental rehabs, "To use, or not to use: that (still) is the question.". PMID- 20298647 TI - Antibacterial properties of pit and fissure sealants combined with daily fluoride mouth rinse. AB - PURPOSE: Pit and fissure sealants are widely used in the prevention of initial occlusal caries. The purpose of this study was to determine whether fluoride releasing pit and fissure sealants regain their antibacterial properties after rinsing with a fluoride solution. METHOD: Helioseal F, Ultraseal XT, Dyract Seal, and GC Fuji TRIAGE were placed on the sidewalls of the wells of a 96-microtiter plate. After polymerization and a 30 day aging process, the samples were rinsed daily with a 0.05% NaF solution for 14 days. Twenty four hours after the last fluoride rinse, freshly grown Streptococcus mutans cells (circa 1 x 106) were placed on the surface of each sample for 1 hour at 37 degrees C. Growth medium was then added to each well and bacterial growth was followed for 24 hours in a temperature-controlled spectrophotometer. Similar experiments were conducted on samples 48 hours and 72 hours after the last fluoride rinse. RESULTS: The results showed that both GC Fuji TRIAGE and Dyract Seal possessed antibacterial properties 24 hours after the last fluoride exposure. GC Fuji TRIAGE maintained potent antibacterial properties 48 hours after the last fluoride rinse. 72 hours after the last fluoride rinse none of the materials showed any antibacterial properties. CONCLUSIONS: None of the tested materials showed any antibacterial properties after a 30 day aging process An aging process of all tested sealant materials, for 30 days, resulted in a complete elimination of their antibacterial properties. After a daily 30 second rinse for two weeks with a 0.05% NaF solution, the antibacterial attributes of the glass-ionomer and the compomer based sealants were regained. PMID- 20298648 TI - Determination of the optimum time for surgical removal of unerupted anterior supernumerary teeth. AB - PURPOSE: The purpose of this study was to determine the optimum time for surgical removal of unerupted maxillary anterior supernumerary teeth. METHODS: The study population consisted of 126 children. Stages C to H of the Demirjian classification were used to classify the dental development of the adjacent incisors. Associations were sought between the complications and the developmental stage of the adjacent maxillary incisors at the time of surgical removal. Tests of association were carried out using Fisher's exact test with a probability level of P=.05 for statistical significance. RESULTS: Significant differences were evident: for mature maxillary central incisors (N=170); between all the proportions for root resorption, with the greatest difference being between stages E and H (P<.001); for arrested root development between stages D and E (P=.013), and D and H (P=.02); and for persistent malocclusion between stages E and G (P=.004), E and H (P=.02), F and G (P=.005), and F and H (P=.01). CONCLUSION: Early removal of unerupted maxillary supernumerary teeth seems to be advantageous with a cutoff point of approximately 6 to 7 years old, after which more complications are expected. PMID- 20298649 TI - American Academy of Pediatric Dentistry analysis and policy recommendations concerning mid-level dental providers. PMID- 20298650 TI - Socio-ecological factors associated with returning for post-operative care after dental treatment under general anesthesia. AB - PURPOSE: The aim of this study was to determine if specific variables in a theorized socio-ecological model are associated with returning for post-operative care after dental treatment under general anesthesia. METHODS: A 26 item cross sectional survey assessing socio-ecological variables of 100 families of patients receiving dental treatment under general anesthesia was conducted. Chi-square tests and logistic regressions were used to investigate associations between returning for post-operative care with child, family, clinic and environmental variables described in the proposed socio-ecological model. RESULTS: Forty-seven percent of patients returned for post-operative care. Children without a dental home had lower odds of returning than children referred from a continuous source of care. Children with an ASA II/III classification had lower odds of returning for post-operative care than children who were ASA I. CONCLUSIONS: One child level and one environmental level variable in the theorized socio-ecological model had an impact on whether patients returned for post-operative care after dental treatment under general anesthesia. Further investigation of socio ecological variables influencing dental health behaviors is needed. PMID- 20298651 TI - Effect of milk and soy-based infant formulas on in situ demineralization of human primary enamel. AB - PURPOSE: The effect of infant formulas sweetened or not with sucrose on primary enamel demineralization and dental biofilm is not known. This study's purpose was to evaluate the effect of infant formula and sucrose association on demineralization of primary enamel and dental biofilm formed. METHODS: A cross over, split-mouth, and blind in situ study was conducted during 3 phases, each of 10 days duration, during which 11 volunteers wore palatal appliances containing slabs of human primary enamel. The dental slabs were extraorally subjected 8 times a day to 6 groups of treatment: distilled and deionized water; 10% sucrose solution; and milk-based and soy-based formula with or without 10% sucrose added. After each phase, the acidogenicity, biochemical and microbiological composition of dental biofilm formed was analyzed, and enamel demineralization was assessed by microhardness. RESULTS: Both formulas induced significant enamel mineral loss, which increased when sucrose was added. Both formulas were fermented, resulting in a decrease of biofilm pH, irrespective of sucrose addition. Also, lactobacilli counts were higher in biofilm formed in the presence of both formulas when compared to the water group. CONCLUSIONS: Milk and soy-based formulas present potential to induce demineralization in primary enamel, which increased when sweetened with sucrose. PMID- 20298652 TI - Mineral trioxide aggregate produces superior outcomes in vital primary molar pulpotomy. AB - PURPOSE: The purpose of this study was to investigate the outcomes of vital primary molar pulpotomy when there is no direct contact between eugenol and the vital pulp. Four pulpotomy techniques were compared: (1) ferric sulfate (FS) pulpotomy; (2) eugenol-free FS pulpotomy; (3) mineral trioxide aggregate (MTA) pulpotomy; and (4) FS/MTA pulpotomy. METHODS: The pulpotomy technique assigned to each molar was determined by random selection. Two blinded, disinterested raters classified each molar into 1 of 3 radiographic outcomes: (1) N=normal molar without pathologic change; (2) Po=pathologic change present, follow-up recommended; (3) Px=pathologic change present, extract. RESULTS: A total of 92 patients with 227 pulpotomy-treated molars returned for at least 1 recall examination. Median follow-up for molars was 24 months (range=12-38 months). MTA molars demonstrated significantly fewer Px radiographic outcomes than FS molars (P=.002, chi-square test). Eugenol-free FS molars demonstrated significantly more Px radiographic outcomes than MTA (P<.001, chi-square test) or FS/MTA (P=.002, chi-square test) molars. Significantly lower survival was demonstrated for eugenol-free FS molars compared to MTA molars (P=.02, log-rank test) over 6 to 38 months. CONCLUSIONS: Outcomes for mineral trioxide aggregate pulpotomy were superior to ferric sulfate and eugenol-free ferric sulfate pulpotomy after a median follow-up of 2 years. PMID- 20298653 TI - Behavioral determinants of brushing young children's teeth: implications for anticipatory guidance. AB - PURPOSE: The purposes of this study were to identify parents' motivation, support, and barriers to twice daily tooth-brushing of infants and preschool-age children and to discover new approaches to encourage this important health behavior. METHODS: Qualitative interviews were conducted with 44 rural parents about tooth-brushing habits and experiences. RESULTS: Forty of 44 parents reported that they had begun to brush their child's teeth; 24 (55%) reported brushing twice a day or more. Parents who brushed twice a day, vs less often, were more likely to describe specific skills to overcome barriers; they expressed high self-efficacy and held high self-standards for brushing. Parents who brushed their children's teeth less than twice daily were more likely to: hold false beliefs about the benefits of twice daily tooth-brushing; report little normative pressure or social support for the behavior; have lower self-standards; describe more external constraints; and offer fewer ideas to overcome barriers. CONCLUSIONS: The findings support an integrative framework in which barriers and support for parents' twice daily brushing of their young children's teeth are multiple and vary among individuals. Knowledge of behavioral determinants specific to individual parents could strengthen anticipatory guidance and recommendations about at-home oral hygiene of young children. PMID- 20298654 TI - Amelogenesis imperfecta due to a mutation of the enamelin gene: clinical case with genotype-phenotype correlations. AB - The major protein components of the enamel matrix include the most abundant amelogenin proteins as well as less plentiful proteins such as enamelin and ameloblastin. The enamel defect in amelogenesis imperfecta (Al) generally results in enamel that is too thin (hypoplastic) or too soft (hypocalcification or hypomaturation). Previous reports indicate that mutations in the human enamelin gene (ENAM) cause hypoplastic Al through autosomal-dominant inheritance patterns and patients may also exhibit an anterior open bite. Although crown resorption of unerupted teeth occurs more frequently in Al patients, this finding has not been previously associated with known ENAM mutations. The purpose of this article was to report the genotype-phenotype correlations for a 9-year, 11-month-old boy with a homozygous ENAM mutation (c.1258_1259insAG). PMID- 20298655 TI - A single appliance for the correction of digit-sucking, tongue-thrust, and posterior cross bite. AB - Clinical management of non-nutritive sucking habits and the resulting dentofacial changes often require multiple appliances to correct, leading to increased treatment time and costs. The aim of this paper was to introduce a single appliance combining a Teflon roller, a slow palatal expander, and a tongue crib appliance that is designed to correct the: (1) sucking habit; (2) anterior open bite; (3) posterior crossbite; (4) tongue thrust; and (5) molar relationships without the need for multiple treatment strategies. Moreover, the fixed-removable design ensures patient compliance, yet allows the appliance to be easily removed by the clinician for adjustments. PMID- 20298656 TI - Rubber dam use: a survey of pediatric dentistry training programs and private practitioners. AB - PURPOSE: The benefits of the rubber dam (RD) are well known, but little data on utilization is available. This study's purpose was to evaluate the use of the rubber dam comparing survey responses of postgraduate pediatric dental residency program directors to privately practicing pediatric dentists. METHODS: This prospective, Institutional Review Board-approved, survey-based study was sent to 75 current directors of pediatric dentistry postgraduate programs and a random sample of 200 practicing pediatric dentists identified through a computer generated process. A 22-item survey was developed, pilot tested, and attached to an e-mail sent to the study sample. Surveys were posted and managed at: "www.surveymonkey.com". RESULTS: One hundred fifteen respondents completed the survey. Fifty-six (75%) were program directors, and 59 (30%) were private practitioners. Most respondents felt that the use of RD is considered a standard of care and was emphasized during training. More than 80% stated that they use the RD either always or frequently during daily practice. The most common factors for and against the use of RD were maintaining a dry field and patient anxieties and potential for painful stimulus, respectively. CONCLUSION: This study's results suggest that the use of rubber dams: (1) is considered a standard of care in pediatric dentistry; and (2) may be modified, depending on procedural and/or patient factors. PMID- 20298657 TI - Caries-risk assessment and caries status of children with autism. AB - PURPOSE: This paper's purpose was to describe the caries status of children with autism and explore associations with the Caries-risk Assessment Tool promoted by the American Academy of Pediatric Dentistry. METHODS: Data was collected from children with autism, their parents, and dentists using interviews, surveys, and treatment records. Descriptive statistics and bivariate analysis explored the association of new caries activity and caries experience with oral health measures. RESULTS: Subjects were 75 males and 24 females with a mean age (+/-SD) of 9.7 years (+/-3.7), (range=2.7 to 19 years). Children < or =7 years old had more new caries (60%) than older children (34%; P=.05). Although not statistically significant, all children who brushed less than once per day had new caries and a mean t-DMF-T (def + DMF) of 73. Children with poor oral hygiene had more new caries (59%) than those with good/excellent hygiene (28%; P=.06). Caries status was not associated with gender, socioeconomic status, medical history, appointment type, dental home, food rewards, restricted diets, and some hygiene habits. CONCLUSIONS: This study confirms the validity of considering autism as an indicator of high caries risk. Oral hygiene may be the most influential risk indicator associated with new caries in children with autism. PMID- 20298658 TI - [Surgical treatment in adenocarcinoma of the cardia]. PMID- 20298659 TI - [Distal trachea and bronchial large lesions and suture reinforcement with Polyglicol Acid (PGA) patch. First clinical experience]. AB - BACKGROUND: Iatrogenic lacerations of the trachea and the bronchies are mostly complications of emergent intubations or percutaneous tracheotomies. The outcome is mainly influenced by thorough diagnostics, severity of the lesions, and urgent treatment. New materials are used to reduce the tension at the sutured points during ventilation. PATIENTS AND METHODS: Four patients were operatively treated with primary suturing of trachea and bronchies with Polydioxanon. The large wounds were then covered using resorbable Soft PGA Mesh (resorbable Polyglykol Acid patch). The first two patients were found hypoxic and was orotracheally intubated in an emergency. An air leckage was detected in the hospital due to a large lesion of the pars membranacea. The third patient was operated in an emergency due to ileus caused by progressive colonic carcinoma. The weaning period on Intensive Care Unite (ICU) was unsuccessful. In a difficult procedure she underwent a percutaneous tracheotomy (dystopia of the trachea due to an arteria lusoria) mainly resulting in esophagotracheal fistulae. The fourth patient was treated by esophagectomy due to a local progressive carcinoma. A long lesion between the carina and left main bronchus resulted. All lacerations were treated by single knot suture technique with Polydioxanone and finally covered (patched) with PGA Mesh. The outcome of the surgical treatment was analyzed. RESULTS: In bronchoscopies and CT-scans no air leackages during respiratory ventilation periods were observed. The first patient could be transferred into a normal ward from ICU at day 38. The second patient was found to be tetraplegic and was discharged into another hospital at day 48. One patient died at the 15th postoperative day due to urosepsis. The fourth patient left the ICU on day 10 and was discharged home at day 23. CONCLUSIONS: Large iatrogenic airway lacerations of the distal trachea should be managed by early surgical repair due to their life-threatening outcome. Although only a small number of patients were analyzed so far, a PGA Mesh might be useful to increase the suture safety reducing the tension at the suture points due to the cuff pressure during long ventilation periods. PMID- 20298660 TI - Biliary tract injuries during laparoscopic cholecystectomy: three case reports and literature review. AB - INTRODUCTION: Biliary tract injuries (BTI) represent the most serious and potentially life-threatening complication of cholecystectomy. During open cholecystectomies (OC), the prevalence of bile duct injuries has been estimated at only 0.1-0.2%. We report 3 cases of BTI during laparoscopic cholecystectomy (LC). CASE 1: Ascalesi Hospital, Naples 2003-2007, 875 LC (BTI 0,11%). During the dissection of triangle of Calot a partial resection of biliary common duct was made. Immediately the lesion was evident and sheltered in laparoscopy, suturing with a spin reabsorbable, without biliar drainage. The post-operative outcome was good, without alteration of the some parameters, and the patient was discharged after three days. At the last follow-up (January 2006) the cholangiography didn't show stricture or leakage. CASE 2: General and Laparoscopic Surgical Unit San Giovanni di Dio Hospital Frattamaggiore 2004-2007, 720 LC (BTI 0,13%). Patient affected by cholecystitis with gallstones. The patient did not present jaundice, but abdominal pain, leucocitosis, fever and US evidence of parietal gallbladder inflammation. LC was performed after 36 h; during operation, common biliar duct was misidentified for subverted anatomy caused by inflammation. The common bile duct was clipped, and the patient presented jaundice after three days after operation. The colangiography was performed showing the stop. Therefore a reoperation was needed and laparotomic Roux-en-Y hepaticojejunostomy was performed. CASE 3: Dpt of Emergency Surgery, Second University of Naples 2000 2007, LC 520 (BTI 0,19%). Patient affected by more than 20 years symptomatic cholelithiasis, with only obesity risk factor; she underwent laparoscopic cholecystectomy and sudden bleeding of the cystic artery, poor vision and probably the long history of symptoms, producing a flogistic alteration of the anatomy, caused a misidentification of the cystic duct and the common bile duct with complete or lateral clipping of the common hepatic duct. The error was unrecognized intra-operatively but after progressive jaundice the postoperative colangiography showed a nearly complete stop by two clips. Roux-en-Y hepaticojejunostomy with intraoperative cholangiographic control was performed. DISCUSSION: The most common cause of BTI is the failure to recognize the anatomy of the triangle of Calot. This is attributed to factors inherent to the laparoscopic approach, to inadequate training of the surgeon and to local anatomical risk factors. The laparoscopic "learning curve" of the surgeon is the most important factor of bile ducts injury. But also local anatomical risk factors are important such as acute cholecystitis, severe chronic scarring of the gallbladder and bleeding or excessive fat in the hepatic hilum. These local risk factors seem to be present in 15% to 35% of BTI. Abnormal biliary anatomy, such as a short cystic duct or a cystic duct entering into the right hepatic duct also may increase the incidence of BTI. Schematic representation of the common mechanisms of BTI during LC are: misidentification of the cystic duct and the common biliary duct, lateral clipping of the common biliary duct, traumatic avulsion the cystic duct junction, diatermic injury of common biliary duct during dissection of the Calot triangle or during the cholecystectomy, injury of anomalous right hepatic duct. CONCLUSION: Conversion to laparotomy, in difficult cases involving inflammatory changes, aberrant anatomy or excessive bleeding, is not to be considered as a failure but rather as good surgical decision in order to ensure the patient's safety. PMID- 20298661 TI - Multifocality of thyroid carcinomas: a "privilege" of papillary tumors or not? AB - AIM: To study the frequency of multifocality in well-differentiated non-medullary thyroid carcinomas and correlate it with various epidemiological factors, as well as with patients' survival. PATIENTS AND METHODS: A retrospective study was conducted on 80 patients who underwent total thyroidectomy from January 1985 to December 2004 in the First Department of Surgery of University General Hospital of Alexandroupolis, Democritus University of Thrace, Greece, for well differentiated non-medullary thyroid cancer (papillary and follicular). Patients' medical records and demographics, including age, gender, histological type (papillary, follicular), multiple foci of tumors, overall and specific survival were analyzed. RESULTS: Multifocality was established in 17/80 patients (21,25%). Multifocal tumors were found in 4/20 male patients (20%) and 13/60 female ones (21,67%), percentages which are almost identical. Increased rates of multifocal tumors were found in the age groups of 20-29, 30-39 and 70-79 years old, while low rates were documented in the age groups of 0-9, 10-19 and 60-69 years old. Follicular tumors had a 20% rate, similar to papillary tumors (22,2%), and an impressive multifocal rate of mixed papillary-follicular neoplasms (75%) was found. Finally, survival was not found to be influenced by the multifocality of the tumor, under the prerequisition that total thyroidectomy is applied. CONCLUSIONS: Multifocality should not be considered as a "privilege" of papillary thyroid tumors, but as a privilege of thyroid carcinomas in general. If total thyroidectomy is applied in all benign and malignant thyroid diseases, the presence of multiple foci does not affect the prognosis and the survival of the patients. PMID- 20298662 TI - A rare case of extraskeletal osteosarcoma of the esophagus: an example of difficult diagnosis. AB - Sarcomatous lesions of the esophagus are rare. We describe a controversial case of a malignant aggressive tumor of the aesophagus, with a very poor prognosis and rapid outcome for the patient. A 74-year-old man underwent endoscopic examination for recurrent thoracic pain and dysphagia. A 8 cm mass was found in the cervical esophagus. A sarcomatous tumor with osteoid aspects was observed on the histopathological examination, without any carcinomatous component. PMID- 20298663 TI - [Unusual cause of acute abdomen in adult patient: gallstone ileus]. AB - INTRODUCTION: Gallstone ileus is a rare complication of cholecystolithiasis. It causes 1-3% of the mechanical obstructions of the small bowel. It often affects patients between 63 and 85 years old. Pre-operative diagnosis is usually delayed 1-10 days because there is not a specific symptomatology. CASE REPORT: The authors report the case of a 50 year-old man with diagnosis of mechanical obstruction of the small bowel caused by a voluminous gallstone. Ileal occlusion was showed by CT. The patient underwent to one-stage emergency surgery with enterolithotomy, cholecystectomy and duodenal fistula repair. Patient's recovery was regular and he was discharged fourteen days after surgery. DISCUSSION: In our case gallstone ileus was diagnosed with a delay of 5 days. Ultrasonography was not able to show the gallbladder. Diagnosis was made by CT, which is the diagnostic gold standard. CONCLUSION: Patient's performance status influences surgical strategy. In our experience, the patient underwent one-stage surgery because he was considered at low risk. Instead staged procedure with enterolithotomy and delayed cholecystectomy and fistula repair, is performed only in patients at high risk. PMID- 20298664 TI - [Surgical treatment of non-metastatic gastric GIST: two cases and review of the literature]. AB - Gastro-Intestinal Stromal Tumors (GISTs) represent an evolving field in oncological surgery and must be approached with specific prognostic and therapeutic criteria. In the GIST's suspicion the surgeon has to consider all the therapeutic possibilities, also for the impossibility to predict the biological behaviour and the aggressiveness of the tumor. The presence of a GIST has to be suspected in patients observed for gastrointestinal bleeding, when another pathology isn't demostrable. Surgical strategy must consider a limited resection as the best treatment, differently from what we do for adenocarcinoma. The extension of the resection can changes, regarding tumor volume and position, from extremely invasive surgery to laparoscopic operations with a partial removal of the gastric wall. Lymphadenectomy is not indicated because these tumors rarely spread to the nodes. We present the clinical case of two patients observed for gastrointestinal bleeding and with preoperative diagnostic suspicion of GIST, submitted to surgical resection. In the first case we performed a superior polar gastrectomy with esofago-gastric anastomosis for the mass proximity to the cardias. In the second patient the intervention has been a limited resection of the fundus of stomach including the tumor. PMID- 20298665 TI - [Intestinal perforation due to accidental ingestion of foreign bodies]. AB - Usually the ingested foreign bodies (IFB) pass the gastrointestinal tract making no lesions. Sometimes IFB could lead to a gastrointestinal perforation. The most frequently perforating IFB are chicken or fish bones and toothpicks, while risks factors are mental retardation, alcohol or drug abuse, denture usage, quick eating or habitual chewing of toothpicks. The accidentally ingestion in a high risk patient with unclear symptoms, added to a low sensitive diagnostic imaging, lead to intraoperative diagnosis in one half cases of gastrointestinal perforation by IFB. Furthermore the surgical treatment range between the less minimal invasive laparoscopic IFB extraction and intraabdominal hole suture to a laparotomic bowel or colic resection. Herein we describe our experience in 3 cases of gastrointestinal perforation by IFB have been diagnosed at surgery and treated by IFB extraction and hole suture (in 2 patients; 1 laparoscopy, 1 laparotomy) or open right emicolectomy (1 patient). PMID- 20298666 TI - [Role of ERCP in the era of videolaparoscopic cholecystectomy. Personal experience]. AB - INTRODUCTION: In subjects operated by videolaparoscopic cholecystectomy (VLC) incidence of synchronous cholecysto-choledochal stones is 7-20%. Aim of the study is to report our experience in endoscopic treatment of common bile duct (CBD) stones before VLC (sequential treatment). PATIENTS AND METHODS: From January 2001 to May 2007, 189 ERCP for synchronous cholecysto-choledochal stones were performed with analgo-sedation. In selected cases antibiotics and protease inhibitors were used. RESULTS: CBD clearance was 100%. The incidence of complications (mild, moderate and severe) was 8.2%, mortality 0.53% (1 patient). We observed 31 cases of transient asymptomatic hyperamilasemia (16.4%). A total of 186 subjects were operated by VLC, with only 3 conversion, without procedure related mortality. CONCLUSIONS: In our opinion, the best treatment of syncronous cholecisto-choledochal stones is related to available tools and human experience, but for an experienced surgical and endoscopic team the sequential approach is feasible, safe and effective. PMID- 20298667 TI - [Total intradermal suture techniques]. AB - Two kind of total intradermal suture techniques are described in the present report. These procedures allow an effective reduction of post-operative pain of surgical wound, prevent infections, cut down tissutal trauma, achieve better aesthetic results, making easier postoperative patient's management. From January 2001 to December 2007, 1,427 patients underwent surgical treatment and the wounds have been sewn with self-locking knots or intradermal skin closure with introflecting knots. This kind of procedures allow a sharp reduction of postoperative pain as well as the incidence of wound infections. Also the number of wound medication required after surgery is significantly reduced. PMID- 20298668 TI - How to prevent intraoperative risks and complications in laparoscopic splenectomy. AB - Since its introduction in 1992 laparoscopic splenectomy (LS) has become the technique of choice for surgical removal of the spleen in several centres. The procedure, however, is associated with risks and complications, either during surgery or in the postoperative phase. Although the incidence of intraoperative complications is unknown, intraoperative risks in patients undergoing laparoscopic splenectomy are not uncommon. In this article, we reviewed the literature on risks and complications during LS, and we point out, based on our personal series and on the experiences reported by other Authors, how to prevent, whenever possible, these complications. PMID- 20298669 TI - The effect of transcatheter arterial embolisation for nonvariceal upper gastrointestinal bleeding. AB - INTRODUCTION: The aim of this investigation was to evaluate the clinical efficacy and safety of transcatheter arterial embolisation with coils for nonvariceal upper gastrointestinal (GI) bleeding after failed endoscopic therapy. MATERIAL AND METHODS: Between 2007 and 2009, transcatheter arterial embolisation was performed in 40 patients. We evaluated the angiographic and clinical success rate, recurrent bleeding rate, procedure-related complications and clinical outcomes. RESULTS: Primary technical success was achieved in all patients. In 82% of the patients, haemostasis was achieved with clinical improvement and without need for further therapy. There were no ischaemic GI complications. Recurrent bleeding occurred in seven patients (18%) within the first week after treatment, and in three cases these were managed successfully with a second embolisation. The overall 30-day mortality rate was 18%, and mortality related to bleeding was 10%. The mean follow-up period was 13 months (range 1-31 months). Non-bleeding related mortality was 15% in the follow-up period. There were no hospital readmissions due to upper GI bleeding. CONCLUSION: Transcatheter arterial embolisation for upper GI bleeding is a safe and effective minimally invasive method, but it entails relatively high rates of early rebleeding as well as relatively high mortality rates both related to GI bleeding and to non-GI bleeding causes. PMID- 20298670 TI - Immune activation in chronic HIV infection. PMID- 20298671 TI - A fluorescence correlation spectroscopy-based assay for fragment screening of slowly inhibiting protein-peptide interaction inhibitors. AB - A fluorescence correlation spectroscopy (FCS)-based competitive binding assay to screen fragment-size compounds that weakly and slowly inhibit protein-peptide interactions was established. The interactions were detected by the increased diffusion time of a fluorescently labeled peptide probe after binding to its interacting protein. We analyzed the interactions between the c-Cbl TKB domain and phosphopeptides derived from ZAP-70, APS, and EGFR with the FCS assay and obtained 6 hit fragments that bound to the c-Cbl interaction sites. The binding amounts of the fragments were measured by direct binding measurements using surface plasmon resonance, and 5 fragments were found to bind selectively. The effect of 2 of the 5 fragments on the interaction with c-Cbl and the peptide exhibited strong time dependency. Furthermore, the inhibition by the selected 5 fragments on the protein-peptide interaction was confirmed by their effect on pull-down assays of c-Cbl with the biotin-conjugated interaction peptides. These results indicate the advantage of our FCS-based assay to study the time-dependent binding of compounds to their target protein. PMID- 20298672 TI - Efficient ligation and cloning of DNA fragments with 2-bp overhangs. AB - Various methods of ligation are currently available and routinely used by molecular biologists, such as blunt end ligation, cohesive end (two and four overhangs), and ligation of Taq polymerase-derived products. However, there is no efficient method for the cloning of DNA fragments with 2-bp overhangs. We present a simple method for the efficient ligation of DNA fragments with 2-bp overhanging ends, ranging in size from 0.7 to 2.5 kbp. Our method involves the initial heating and flash freezing of the vector-insert DNA mix, and a subsequent unique ligation reaction. This method provides a new molecular biology tool for researchers. PMID- 20298673 TI - p73 and p63 regulate the expression of fibroblast growth factor receptor 3. AB - p53, p63 and p73 make a family of transcription factors that play a vital role in development and cancer. All p53 family members have more than one promoter producing Transactivating (TA) and Dominant Negative (DeltaN) isoforms and their mRNAs are subjected to extensive splicing at 3' end to produce multiple protein products. p53 is usually inactivated by point mutations during tumorigenesis, whereas the expression levels and p63 and p73 are modulated to give tumor cells a selective advantage. In this study, aiming to find novel targets of the p53 family members, we identified FGFR3 as a gene transcriptionally controlled by p63 and p73. FGFR3 has been implicated in development and tumor biology as activating mutations of this gene was described in skeletal disorders, non-invasive skin conditions and superficial bladder cancers. We found that TAp73, TAp63 and DeltaNp63 was capable of inducing FGFR3. siRNA mediated downregulation of DeltaNp63 decreased endogenous FGFR3 protein levels. Our findings of this new link between p53 family proteins and FGFR3 may help understanding the transition of superficial bladder cancers to an invasive phenotype. PMID- 20298674 TI - DRR1 is expressed in the developing nervous system and downregulated during neuroblastoma carcinogenesis. AB - Down-regulated in renal cell carcinoma 1 (DRR1) is mapped at 3p21.1, and is a candidate tumor suppressor gene. However, its biological roles have yet to be elucidated. Here, we developed polyclonal antibodies against DRR1 protein, and examined its expression during embryogenesis and carcinogenesis. The DRR1 protein was preferentially expressed in axonal projections of the central and peripheral nervous system of mice during embryonic days 10.5-16.5. Consistent with this expression pattern, the protein was detected in the neurites of primary cultured cortical neurons of rats at embryonic day 18.5. Survival of these cells was significantly inhibited by RNAi-induced downregulation of DRR1 expression. DRR1 was poorly expressed in established cancer cell lines, including neuroblastoma cells, whereas strong expression was observed in normal cells. A neuroblastoma model, MYCN transgenic mice, revealed that DRR1 protein was expressed in the celiac ganglion 2 weeks after birth when neuroblast hyperplasia was also observed; however, there was no longer any expression of DRR1 protein in tumors originating from the ganglion 8 weeks after birth. Together, our data indicate that DRR1 protein is expressed in normal cells, particularly in the nervous system during embryogenesis, is involved in neuronal cell survival, and is downregulated during neuroblastoma carcinogenesis. PMID- 20298676 TI - Troglitazone is an estrogen-related receptor alpha and gamma inverse agonist. AB - As a ligand for peroxisome proliferators-activated receptor gamma (PPAR gamma), troglitazone inhibits cell growth by mechanisms besides activating PPAR gamma. In this study, we found that troglitazone interfered with the interactions between estrogen-related receptor alpha and gamma (ERR alpha and ERR gamma) and their coactivator PPAR gamma coactivator-1 alpha (PGC-1 alpha) functioning as an inverse agonist. Additionally, troglitazone suppressed the expressions of PGC-1 alpha and its related member PGC-1 beta which are key regulators of mitochondrial function. Consequently, troglitazone reduced mitochondrial mass and suppressed the expressions of superoxide dismutases to elevate reactive oxygen species (ROS) production. The increase in ROS in turn induced the expression of cell cycle inhibitor p21(WAF1). We therefore propose that ERR alpha and ERR gamma are alternative targets of troglitazone important for mediating its growth suppressive effect. PMID- 20298675 TI - Direct assessment of P-glycoprotein efflux to determine tumor response to chemotherapy. AB - Multidrug resistance is a major impediment to the success of cancer chemotherapy. The overproduced P-glycoprotein that extrudes anticancer drugs from cells, is the most common mechanism detected in multidrug-resistant cancers. Direct measurement of cellular efflux of tumors in vivo, rather than estimation of MDR1 mRNA and P glycoprotein levels in samples stored or embedded, can functionally characterize the mechanism of drug resistance and determine the choice of anticancer drugs for cancer patients. Herewith, we introduce a new approach to directly determine P glycoprotein efflux of tumors. Employing Flutax-2 (Oregon green-488 paclitaxel) and fluorescence spectrophotometry, this method has successfully measured cellular transportability including efflux and accumulation in diverse cancer cell lines, tumors and other tissues with high reproducibility. With this method, we have quantitatively determined cellular efflux that is correlated with P glycoprotein levels and the reversal effects of agents in cell lines of breast, ovarian, cervical and colon cancers, and in tumor-bearing mice. It has sensitively detected these alterations of P-glycoprotein efflux in approximately 5mg tumor or other tissues with high confidence. This direct and quick functional assessment has a potential to determine drug resistance in different types of cancers after surgical resection. Further validation of this method in clinic settings for the diagnosis of drug resistance purpose is needed. PMID- 20298677 TI - Rosiglitazone, an agonist of peroxisome proliferator-activated receptor gamma, decreases immunoreactivity of markers for cell proliferation and neuronal differentiation in the mouse hippocampus. AB - In the present study, we investigated the regulating effects of rosiglitazone (RSG), a synthetic agonist of peroxisome proliferator-activated receptor gamma, treatment for 28days on the cell proliferation and neuronal differentiation in the mouse hippocampal dentate gyrus by 5-bromo-2'-deoxyuridine (BrdU), Ki67 and doublecortin (DCX) immunohistochemistry. These markers were detected in the subgranular zone (SGZ) of the dentate gyrus in vehicle- and RSG-treated groups. In the RSG-treated group, the number of BrdU-, Ki67- and DCX-immunoreactive cells was significantly decreased compared to those in the vehicle-treated group. In addition, brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor levels were significantly decreased in the dentate gyrus of the RSG-treated groups compared to the vehicle-treated group. These results indicate that RSG treatment decreases immunoreactivities of markers for cell proliferation and neuronal differentiation and levels of neurotrophic factors in the SGZ of the hippocampal dentate gyrus. PMID- 20298679 TI - Word accents and morphology--ERPs of Swedish word processing. AB - Results indicating that high stem tones realizing word accents activate a certain class of suffixes in online processing of Central Swedish are presented. This supports the view that high Swedish word accent tones are induced onto word stems by particular suffixes rather than being associated with words in the mental lexicon. Using event-related potentials, effects of mismatch between word accents and inflectional suffixes were compared with mismatches between stem and suffix in terms of declension class. Declensionally incorrect suffixes yielded an increase in the N400, indicating problems in lexical retrieval, as well as a P600 effect, showing reanalysis. Both declensionally correct and incorrect high tone inducing (Accent 2) suffixes combined with a mismatching low tone (Accent 1) on the stems produced P600 effects, but did not increase the N400. Suffixes usually co-occurring with Accent 1 did not yield any effects in words realized with the nonmatching Accent 2, suggesting that Accent 1 is a default accent, lacking association with any particular suffix. High tones on Accent 2 words also produced an early anterior positivity, interpreted as a P200 effect reflecting preattentive processing of the tone. PMID- 20298678 TI - Organophosphate exposure during a critical developmental stage reprograms adenylyl cyclase signaling in PC12 cells. AB - Early-life organophosphate (OP) exposures elicit neurobehavioral deficits through mechanisms other than inhibiting cholinesterase. Cell signaling cascades are postulated as critical noncholinesterase targets that mediate both the initial alterations in neurodevelopment as well as subsequent abnormalities of synaptic function. We exposed PC12 cells to chlorpyrifos, diazinon or parathion in the undifferentiated state and during neurodifferentiation; we then assessed the function of the adenylyl cyclase (AC) signaling cascade, measuring basal AC activity as well as responses to stimulants acting at G-proteins or on the AC molecule itself. In undifferentiated cells, a 2day exposure to the OPs had no significant effect on AC signaling but the same treatment in differentiating cells produced deficits in all AC measures when exposure commenced at the initiation of differentiation. However, when exposure of the differentiating cells was continued for 6days, AC activities then became supranormal. The same increase was obtained if cells were exposed only for the first two days of differentiation, followed by four subsequent days without the OPs. Furthermore, the OP effects on cell signaling were entirely distinct from those on indices of cell number and neurite outgrowth. These results indicate that OP exposure reprograms the AC pathway during a discrete developmental stage at the commencement of neurodifferentiation, with effects that continue to emerge after OP exposure is discontinued. Importantly, the same sequence is seen with OP exposures in neonatal rats, indicating that direct effects of these agents to reprogram cell signaling provide a major mechanism for functional effects unrelated to cholinesterase inhibition. PMID- 20298680 TI - Slow age-dependent decline of doublecortin expression and BrdU labeling in the forebrain from lesser hedgehog tenrecs. AB - In addition to synaptic remodeling, formation of new neurons is increasingly acknowledged as an important cue for plastic changes in the central nervous system. Whereas all vertebrates retain a moderate neuroproliferative capacity, phylogenetically younger mammals become dramatically impaired in this potential during aging. The present study shows that the lesser hedgehog tenrec, an insectivore with a low encephalization index, preserves its neurogenic potential surprisingly well during aging. This was shown by quantitative analysis of 5 bromo-2'-deoxyuridine (BrdU) immunolabeling in the olfactory bulb, paleo-, archi , and neocortices from 2- to 7-year-old animals. In addition to these newly born cells, a large number of previously formed immature neurons are present throughout adulthood as shown by doublecortin (DCX) immunostaining in various forebrain regions including archicortex, paleocortex, nucleus accumbens, and amygdala. Several ventricle-associated cells in olfactory bulb and hippocampus were double-labeled by BrdU and DCX immunoreactivity. However, most DCX cells in the paleocortex can be considered as persisting immature neurons that obviously do not enter a differentiation program since double fluorescence labeling does not reveal their co-occurrence with numerous neuronal markers, whereas only a small portion coexpresses the pan-neuronal marker HuC/D. Finally, the present study reveals tenrecs as suitable laboratory animals to study age-dependent brain alterations (e.g., of neurogenesis) or slow degenerative processes, particularly due to the at least doubled longevity of tenrecs in comparison to mice and rats. PMID- 20298681 TI - Neural correlates of cross-domain affective priming. AB - The affective priming effect has mostly been studied using reaction time (RT) measures; however, the neural bases of affective priming are not well established. To understand the neural correlates of cross-domain emotional stimuli presented rapidly, we obtained event-related potential (ERP) measures during an affective priming task using short SOA (stimulus onset asynchrony) conditions. Two sets of 480 picture-word pairs were presented at SOAs of either 150ms or 250ms between prime and target stimuli. Participants decided whether the valence of each target word was pleasant or unpleasant. Behavioral results from both SOA conditions were consistent with previous reports of affective priming, with longer RTs for incongruent than congruent pairs at SOAs of 150ms (771 vs. 738ms) and 250ms (765 vs. 720ms). ERP results revealed that the N400 effect (associated with incongruent pairs in affective processing) occurred at anterior scalp regions at an SOA of 150ms, and this effect was only observed for negative target words across the scalp at an SOA of 250ms. In contrast, late positive potentials (LPPs) (associated with attentional resource allocation) occurred across the scalp at an SOA of 250ms. LPPs were only observed for positive target words at posterior parts of the brain at an SOA of 150ms. Our finding of ERP signatures at very short SOAs provides the first neural evidence that affective pictures can exert an automatic influence on the evaluation of affective target words. PMID- 20298683 TI - The specificity of memory for a highly trained finger movement sequence: Change the ending, change all. AB - How are highly trained movement sequences represented in long-term memory? Here we show that the gains attained in the performance of a well-trained sequence of finger movements can be expressed only when the order of the movements is exactly as practiced. Ten young adults were trained to perform a given 5-element sequence of finger-to-thumb opposition movements with their left hand. Movements were analyzed using video based tracking. Three weeks of training resulted, along with improved accuracy, in robustly shortened movement times as well as shorter finger to-thumb touch times. However, there was little transfer of these gains in speed to the execution of the same component movements arranged in a new order. Moreover, even when the only change was the omission of the one before final movement of the trained sequence (Omit sequence), the initial movements of the sequence were significantly slowed down, although these movements were identical to the initial movements of the trained sequence. Our results support the notion that a well-trained sequence of finger movements can be represented, in the adult motor system, as a singular, co-articulated, unit of movement, in which even the initial component movements are contingent on the subsequent, anticipated, ones. Because of co-articulation related anticipatory effects, gains in fluency and accuracy acquired in training on a specific movement sequence cannot be expressed in full in the execution of the trained component movements or of a full segment of the trained sequence, if followed by a different ending segment. PMID- 20298682 TI - SNP improves cerebral hemodynamics during normotension but fails to prevent sex dependent impaired cerebral autoregulation during hypotension after brain injury. AB - Traumatic brain injury (TBI) is a leading cause of morbidity in children and boys are disproportionately represented. Hypotension is common and worsens outcome after TBI. Previous studies show that adrenomedullin, a cerebrovasodilator, prevented sex dependent impairment of autoregulation during hypotension after piglet fluid percussion brain injury (FPI). We hypothesized that this concept was generalizable and that administration of another vasodilator, sodium nitroprusside (SNP), may equally improve CBF and cerebral autoregulation in a sex dependent manner after FPI. SNP produced equivalent percent cerebrovasodilation in male and female piglets. Reductions in pial artery diameter, cortical CBF, and cerebral perfusion pressure (CPP) concomitant with elevated intracranial pressure (ICP) after FPI were greater in male compared to female piglets during normotension which was blunted by SNP. During hypotension, pial artery dilation (PAD) was impaired more in the male than the female after FPI. However, SNP did not improve hypotensive PAD after FPI in females and paradoxically caused vasoconstriction in males. SNP did not prevent reductions in CBF, CPP or autoregulatory index during combined hypotension and FPI in either sex. SNP aggravated ERK MAPK upregulation after FPI. These data indicate that despite prevention of reductions in CBF after FPI, SNP does not prevent impairment of autoregulation during hypotension after FPI. These data suggest that therapies directed at a purely hemodynamic increase in CPP will fail to improve outcome during combined TBI and hypotension. PMID- 20298684 TI - No association of the C>T polymorphism that is located 1385 upstream from initial code of fibroblast growth factor 1 gene with Alzheimer's disease in Chinese. AB - Several lines of evidence indicate that fibroblast growth factor 1 (FGF1) confers neuroprotection against excitotocity and contributes to the selective vulnerability of neurons in entorhinal cortex in Alzheimer's disease (AD). Especially, FGF1 is related to Apolipoprotein E (ApoE) expression in reactive astrocytes. Therefore, FGF1 is a promising candidate gene for AD. Two studies reported the association of a polymorphism that is located 1385bp upstream from the initial code of FGF1 gene (FGF1 -1385 C>T) polymorphism with AD. To determine whether this polymorphism could affect AD development, we investigated the association between this polymorphism and AD risk in 372 sporadic AD patients and 349 controls in a Chinese Han population. No significant difference of allele and genotype distributions between the AD cases and the controls was observed in the total samples (for the alleles, chi(2)=0.126; p=0.722; for the genotypes, chi(2)=0.089; p=0.765), neither when the samples were stratified by ApoE epsilon4 carrying status, age/age at onset and gender. Our data suggested no association between the FGF1 -1385 C>T polymorphism and AD risk in Chinese Han population. PMID- 20298685 TI - Over time, high-sensitivity TnT replaces NT-proBNP as the most powerful predictor of death in patients with dialysis-dependent chronic renal failure. AB - BACKGROUND: Cardiac biomarkers are emerging as a potentially powerful prognostic tool for renal-dialysis patients. The optimal biomarker and/or combination of biomarkers for predicting mortality remain uncertain. This study evaluates the prognostic value of the new high-sensitivity troponin T (TnT) assay compared to established biomarkers. METHODS: All patients had blood sampled for prospective assessment of the prognostic value of traditional risk markers including albumin and CRP, and cardiac biomarkers BNP, NT-proBNP, TnT and TnI. Patients were closely monitored clinically. Mortality and morbidity outcomes were documented for a national morbidity and mortality database. Stored samples were subsequently used to measure TnT with a new high-sensitivity assay. RESULTS: After a median of 30 months from blood collection, NT-proBNP was the most powerful predictor of all cause mortality, along with albumin. After a median of 46.7 months the new high sensitive TnT assay was the only cardiac biomarker predictive of all-cause mortality. TnT was detectable in all dialysis patients using the high-sensitive TnT assay with a cut-point of 24.15 ng/L below which all patients survived. CONCLUSIONS: The new hs-TnT is the most powerful biomarker for prognostic classification for all-cause mortality of all the commonly used biomarkers for our renal-dialysis population. Our study also suggests that cardiac biomarkers have a different prognostic ability for different time frames with NT-proBNP being a better predictor for early mortality and troponin for later mortality. PMID- 20298686 TI - Foreward. Special issue in memoriam: Armand M. Karow Jr., Ph.D. (1941-2007). PMID- 20298687 TI - Inflammatory response and dynamics of lung T cell subsets in Th1, Th2 biased and Th2 deficient mice during the development of hypersensitivity pneumonitis. AB - It is considered that hypersensitivity pneumonitis (HP) occurs with a Th1 cell dominance; however, the role of Th1/Th2 balance is still unclear. C57BL/6 (Th1 biased), BALB/c wt (Th2-biased) and BALB/c Stat6-/- (Th2 deficient) mice were treated with Saccharopolyspora rectivirgula (SR) or saline during 3 weeks, and sacrificed 1 and 4 days (early and late response) after the last administration. Lung isolated T cell subpopulations were analyzed and lung damage extent was quantified. C57BL/6 wt mice exhibited a significant increase in the extent of lung damage when sacrificed at 4 days compared with those sacrificed 1 day after the last SR administration. In contrast, BALB/c wt mice showed a progressive decrease in the extent of lung damage. A significant increase of NKT CD4+ subset was found in C57BL/6 mice while NKT DN cells were increased in BALBc wt mice. Also, NK and gammadelta T cells were increased in BALB/c mice at 1 and 4 days. Stat6-/- mice behave similar to the C57BL/6 mice, showing a progressive increase in the extent of lung damage. A significant increase in the levels of Th1 and Th2 cytokines was observed in bronchoalveolar lavage from the SR-treated mice. These results confirm a predominant role of the Th1 response in HP and suggest that the control of inflammation by Th2 biased mice may be related with the increase of NKT DN cells and regulatory NK and gammadelta T cells. PMID- 20298688 TI - Identification of a lysine-rich region of Fas as a raft nanodomain targeting signal necessary for Fas-mediated cell death. AB - Fas interaction at the plasma membrane with its lipid and protein environment plays a crucial role in the early steps of Fas signalling induced by Fas ligand binding. Particularly, Fas localisation in the raft nanodomains, ezrin-mediated interaction with the actin cytoskeleton and subsequent internalization are critical steps in Fas-mediated cell death. We identified a lysine-rich region (LRR) in the cytoplasmic, membrane-proximal region of Fas as a key determinant modulating these initial events. Through a genetic approach, we demonstrate that Fas LRR represents another signal additional to palmitoylation targeting Fas to the raft nanodomains, and modulates Fas interaction with the cytoskeleton. PMID- 20298689 TI - Potential anti-angiogenic role of Slit2 in corneal neovascularization. AB - Slits are large secreted proteins critical for axon guidance and neuronal precursor cell migration in nervous system. Evidence suggests that classical neuronal guidance cues also regulate vascular development. Our objective was to investigate whether neuronal guidance cue Slit2 and Roundabout (Robo) receptors are involved in corneal neovascularization (NV). Corneal NV model in rats was induced by implantation of agarose-coated gelfoam pellets containing basic fibroblast growth factor (bFGF) into corneal stroma. Differential expression of Slit2 and Robo1-4 between normal and neovascularized cornea was detected by real time RT-PCR and visualized by immunohistochemistry and in situ hybridization. Primary human umbilical vein endothelial cells (HUVECs) were harvested and their expression of Robo1-4 was detected by RT-PCR. Recombinant human Slit2 protein was prepared and the effect of it on the migration of vascular endothelial cells was examined using cell migration assay. Agarose-coated gelfoam pellets were able to induce well-localized and reproducible corneal NV model. A significant down regulation of Slit2 and a strong up-regulation of Robo1 and Robo4 were seen in neovascularized cornea when compared with normal cornea (P < 0.05). Slit2, Robo1 and Robo4 were throughout the epithelium in normal cornea and markedly weak or absent in epithelium in neovascularized cornea, with Robo1 and Robo4 being prominent in vascular endothelial cells invading the stroma. Primary HUVECs were confirmed to express both Robo1 and Robo4 receptors and their migration was inhibited by Slit2 (P < 0.05). This is the first study to assess the association between Slit2 and corneal NV. Our findings suggest that the interaction of Slit2 with Robo1 and Robo4 receptors plays an essential role in inhibiting pathological neovascular processes of the cornea and may represent a new therapeutic target for corneal NV. PMID- 20298690 TI - Pigment epithelium-derived factor inhibits erythropoietin-induced retinal endothelial cell angiogenesis by suppression of PI3K/Akt pathway. AB - Erythropoietin (EPO) plays a critical role in the vascular system and exhibits angiogenic activity in endothelial cells (ECs) such as stimulation of cell proliferation, migration and tube formation in vitro. EPO is the major regulator of cell proliferation and differentiation of erythroid precursors and there by preventing the apoptosis. Pigment epithelial derived factor (PEDF) is a potent anti-angiogenic factor whose effects are partially mediated through the induction of EC apoptosis. The mechanism of EPO and PEDF in retinal neovascularization has not been well documented yet. The effect of EPO and PEDF on cell proliferation was determined by MTT assay. In vitro wound-scratch assay was performed to study the migration of ECs and in vitro tube formation was assessed by the on-gel assay system using gelatin. Inhibitor assay was carried out using LY294002, a phosphatidylinositol 3-kinase (PI3K) inhibitor. Further, PI3K/Akt activity was assessed by transient transfection assay using constitutively active (CA) and dominant negative (DN) Akt mutants. Dextran permeability assay was performed to determine the vascular permeability. We report that EPO stimulates EC proliferation, migration, tube formation and permeability whereas PEDF inhibits the EPO-induced ECs proliferation and permeability. Over expression of DN Akt blocked EPO stimulation of proliferation and permeability, while over expression of CA Akt rescues the inhibitory effect of PEDF on proliferation and permeability. These results demonstrate that PEDF may inhibit the EPO-induced proliferation and permeability via PI3K/Akt-dependent pathway. PMID- 20298691 TI - RNAi targeting micro-calpain increases neuron survival and preserves hippocampal function after global brain ischemia. AB - The calpain family of cysteine proteases has a well-established causal role in neuronal cell death following acute brain injury. However, the relative contribution of calpain isoforms has not been determined in in vivo models. Identification of the calpain isoform responsible for neuronal injury is particularly important given the differential role of calpain isoforms in normal physiology. This study evaluates the role of m-calpain and micro-calpain in an in vivo model of global brain ischemia. Adeno-associated viral vectors expressing short hairpin RNAs targeting the catalytic subunits of micro- or m-calpain were used to knockdown expression of the targeted isoforms in adult rat hippocampal CA1 pyramidal neurons. Knockdown of micro-calpain, but not m-calpain, prevented calpain activity 72 h after 6-min transient forebrain ischemia, increased long term survival and protected hippocampal electrophysiological function. These findings represent the first in vivo evidence that reducing expression of an individual calpain isoform can decrease post-ischemic neuronal death and preserve hippocampal function. PMID- 20298693 TI - Distinct correlations of vasopressin release within the lateral septum and the bed nucleus of the stria terminalis with the display of intermale aggression. AB - Arginine vasopressin (AVP) has been implicated in a wide variety of social behaviors ranging from affiliation to aggression. However, the precise functional involvement of AVP in intermale aggression is still a matter of debate. In fact, very little is known about AVP release patterns within distinct brain regions during the display of intermale aggression and, in turn, the behavioral consequences of such release. We used intracerebral microdialysis to monitor local AVP release within the lateral septum (LS) and the bed nucleus of the stria terminalis (BST) of adult male Wistar rats during the resident-intruder (RI) test. Resident males were cohabitated with a female prior to the RI test to stimulate intermale aggression toward the intruder male. AVP release within the LS correlated positively with intermale aggression. The specific AVP V1a receptor antagonist d(CH(2))(5)Tyr(Me)AVP (10 microg/ml) administered via retrodialysis (3.3 microl/min, 30 min) into the LS of high-aggressive rats prior to the second RI test, prevented an increase in aggression in the second compared with the first RI test as seen in vehicle-treated high-aggressive rats. In contrast to the LS, AVP release within the BST correlated negatively with intermale aggression. Moreover, retrodialysis of synthetic AVP (1 microg/ml) administered into the BST of high-aggressive rats significantly reduced the display of aggression during the second RI test. These data reveal that AVP can both promote and inhibit intermale aggression, depending upon the brain region in which AVP is released. Although challenging the general view that central AVP release enhances intermale aggression in rodents, our data support a model in which AVP coordinates a range of social behaviors by eliciting region-specific effects. PMID- 20298692 TI - Social dominance in male vasopressin 1b receptor knockout mice. AB - We have previously reported that mice with a targeted disruption of their vasopressin 1b receptor gene, Avpr1b, have mild impairments in social recognition and reduced aggression. The reductions in aggression are limited to social forms of aggression, i.e., maternal and inter-male aggression, while predatory aggression remains unaffected. To further clarify the role of the Avpr1b in the regulation of social behavior we first examined anxiety-like and depression-like behaviors in Avpr1b knockout (Avpr1b -/-) mice. We then went on to test the ability of Avpr1b -/- mice to form dominance hierarchies. No major differences were found between Avpr1b -/- and wildtype mice in anxiety-like behaviors, as measured using an elevated plus maze and an open field test, or depression-like behaviors, as measured using a forced swim test. In the social dominance study we found that Avpr1b -/- mice are able to form dominance hierarchies, though in early hierarchy formation dominant Avpr1b -/- mice display significantly more mounting behavior on Day 1 of testing compared to wildtype controls. Further, non socially dominant Avpr1b -/- mice spend less time engaged in attack behavior than wildtype controls. These findings suggest that while Avpr1b -/- mice may be able to form dominance hierarchies they appear to employ alternate strategies. PMID- 20298694 TI - "Green odor" inhalation by stressed rat dams reduces behavioral and neuroendocrine signs of prenatal stress in the offspring. AB - Chronic maternal stress during pregnancy results in the "prenatally stressed" offspring displaying behavioral and neuroendocrine alterations that persist into adulthood. We investigated how inhalation of green odor (a mixture of equal amounts of trans-2-hexenal and cis-3-hexenol) by stressed dams might alter certain indices of prenatal stress in their offspring. These indices were depression-like behavior (increased immobility time in the forced-swim test) and acute restraint stress-induced changes in hypothalamo-pituitary-adrenocortical (HPA) axis activity [plasma corticosterone (CORT) and ACTH levels and the number of Fos-immunoreactive cells in the hypothalamic paraventricular nucleus (an index of neuronal activity)]. Pregnant rats were exposed to restraint stress for 60 min/day for 10 days (gestational days 10-19). The prenatally stressed offspring exhibited significant increases in depression-like behavior and in restraint stress-induced ACTH, CORT, and Fos responses, unless their dam had been exposed to green odor. The behavioral effect of the odor was also seen in offspring that were fostered by unstressed dams. The results obtained in the dams themselves were as follows. In vehicle-exposed stressed dams, but not in green odor-exposed ones, total body and adrenal weights were significantly decreased or increased, respectively. Depression-like behavior was not observed in the vehicle-exposed stressed dams themselves. Green odor inhalation prevented the impairment of maternal behavior induced by restraint stress. Thus, exposure of dams to stress may affect both the fetal brain and fetal HPA axis, and also maternal behavior, leading to altered behavioral and neuroendocrine responses in the offspring. Such effects may be prevented by the stressed dams inhaling green odor. PMID- 20298695 TI - Maternal separation modulates short-term behavioral and physiological indices of the stress response. AB - Early-life stress produces an anxiogenic profile in adulthood, presumably by activating the otherwise quiescent hypothalamic-pituitary-adrenal (HPA) axis during the vulnerable 'stress hyporesponsive period'. While the long-term effects of such early-life manipulations have been extensively characterized, little is known of the short-term effects. Here, we compared the short-term effects of two durations of maternal separation stress and one unseparated group (US) on behavioral and physiological indices of the stress response in rat pups. Separations included 3h on each of 12days, from postnatal day (PND) 2 to 13 (MS2 13) and 3days of daily, 6-h separation from PND11-13 (MS11-13). On PND14 (Experiment 1), both MS2-13 and MS11-13 produced marked reductions in freezing toward an adult male conspecific along with reduced levels of glucocorticoid type 2 (GR) and CRF type-1 (CRF(1)) receptor mRNA in the hippocampus. Group MS2-13 but not MS11-13 produced deficits in stressor-induced corticosterone secretion, accompanied by reductions in body weight. Our results suggest that GR and/or CRF(1) levels, not solely the magnitude of corticosterone secretion, may be involved in the modulation of freezing. In a second experiment, we aimed to extend these findings by testing male and female separated and unseparated pups' unconditioned defensive behaviors to cat odor on PND26, and subsequent cue+context conditioning and extinction throughout postnatal days 27-32. Our results show that maternal separation produced reductions in unconditioned freezing on PND26, with MS2-13 showing stronger deficits than MS11-13. However, separation did not affect any other defensive behaviors. Furthermore, separated rats failed to show conditioned freezing, although they did avoid the no-odor block conditioned cue. There were no sex differences other than weight. We suggest that maternal separation may have produced these changes by disrupting normal development of hippocampal regions involved in olfactory-mediated freezing, not in mechanisms of learning and memory per se. These findings may have direct relevance for understanding the mechanisms by which early-life adverse experiences produce short-term and lasting psychopathologies. PMID- 20298696 TI - One-step assay for quantification of neutralizing antibodies to biopharmaceuticals. AB - Assessment of immunogenicity is an important part of biopharmaceutical drug safety evaluation and a prerequisite for the development of less immunogenic and safer biopharmaceuticals since anti-drug antibodies can impair the activity and compromise the safety of biopharmaceuticals. Although regulatory authorities recommend cell-based assays for detection of neutralizing antibodies (NAbs), such assays are difficult to standardize, and ill adapted to high-throughput analysis. These limitations have been overcome by the development of a unique one-step cell based assay that allows both drug activity and drug NAbs to be quantified rapidly and with a high degree of precision simply be adding reporter cells to a sample. The reporter cells have been engineered to express firefly luciferase (FL) under the control of a drug-responsive promoter, and to express the drug of interest, the production of which is normalized relative to the expression of Renilla luciferase (RL) transcribed from a common doxycycline-inducible promoter. Residual drug levels present in a sample are first quantified by determination of FL expression, autocrine drug synthesis is then induced, and NAb activity is quantified from the difference in the ratio of FL/RL expression in the presence or absence of the sample. Since assay results are normalized relative to the expression of an internal standard, results are independent of cell number or differences in cell viability thus affording a high degree of assay precision and reducing serum matrix effects to a minimum. This unique assay platform is ideally suited for high-throughput analysis, is applicable to most biopharmaceuticals, and will facilitate standardization and comparison of immunogenicity data. The performance of the one-step assay is illustrated for interferon alpha2 (IFNalpha2) used widely to treated chronic hepatitis C (HCV) infection and neoplastic disease. PMID- 20298697 TI - Activation of the cardiac Na(+)-Ca(2+) exchanger by sorcin via the interaction of the respective Ca(2+)-binding domains. AB - Sorcin is a penta-EF-hand protein that interacts with intracellular target proteins after Ca(2+) binding. The sarcolemmal Na(+)/Ca(2+) exchanger (NCX1) may be an important sorcin target in cardiac muscle. In this study, RNAi knockdown of sorcin, purified sorcin or sorcin variants was employed in parallel measurements of: (i) NCX activity in isolated rabbit cardiomyocytes using electrophysiological techniques and (ii) sorcin binding to the NCX1 calcium binding domains (CBD1 and (iii) using surface plasmon resonance and gel overlay techniques. Sorcin is activated by Ca(2+) binding to the EF3 and EF2 regions, which are connected by the D helix. To investigate the importance of this region in the interaction with NCX1, three variants were examined: W105G and W99G, mutated respectively near EF3 and EF2, and E124A that does not bind Ca(2+) due to a mutation at EF3. Downregulation of sorcin decreased and supplementation with wt sorcin (3muM) increased NCX activity in isolated cardiomyocytes. The relative stimulatory effects of the sorcin variants were: W105G>wt sorcin>Sorcin Calcium Binding Domain (SCBD)>W99G>E124A. Sorcin binding to both CBD1 and 2 was observed. In the presence of 50microM Ca(2+), the interaction with CBD1 followed the order W105G>SCBD>wt sorcin>W99G>E124A. In sorcin, the interacting surface can be mapped on the C-terminal Ca(2+)-binding domain in the D helix region comprising W99. The fast association/dissociation rates that characterize the interaction of sorcin with CBD1 and 2 may permit complex formation/dissociation during an excitation/contraction cycle. PMID- 20298698 TI - Malignant and benign mutations in familial cardiomyopathies: insights into mutations linked to complex cardiovascular phenotypes. AB - Cardiomyopathies, familial or sporadic, have become recognized as one of the leading cardiac threats. Hypertrophic cardiomyopathy (HCM) affects 0.2% of the population and is the leading cause of sudden death in young adults. Dilated cardiomyopathy (DCM) and restrictive cardiomyopathy (RCM) are associated with sudden death as well as heart transplantations. Ventricular noncompaction cardiomyopathy (VNCM) is associated with heart failure and arrhythmias. Currently, more than 630 mutations in 10 sarcomeric genes associated with cardiomyopathy have been identified. HCM is associated with more than 550 mutations, whereas DCM, RCM and VNCM are associated with 52, 14 and 17 mutations, respectively. In many cases, the genes affected present a varying range of phenotypic and pathological severity. Recent data suggest that at least two main genetic determinants are involved in the pathogenesis and phenotypic variability within families afflicted by the same disease-linked gene. Individuals that are homozygous for a mutation or heterozygous for two or more mutations often show more severe phenotypes. Secondly, genetic modifiers are present in some cardiomyopathy patients and are associated with a poorer prognosis. At the protein level, changes in protein-protein interactions may also be important in determining the type of cardiomyopathy caused by different mutations. This review provides insight into the complex cardiovascular phenotypes and genetic variability associated with HCM, DCM, RCM and VNCM. PMID- 20298699 TI - Increased phosphorylation of tropomyosin, troponin I, and myosin light chain-2 after stretch in rabbit ventricular myocardium under physiological conditions. AB - After a change in muscle length, there is an immediate intrinsic response in the amount of developed force, followed by a slower response. Although it has been well documented that the slow force response is at least in part generated by modification of calcium handling, it is unclear whether regulation at the myofilament level occurs during the slow force response. We set out to investigate myofilament calcium sensitivity and phosphorylation status of myofilament proteins after a step-wise change in cardiac muscle length. Ultra thin right ventricular intact trabeculae were isolated from New Zealand White rabbit hearts and iontophoretically loaded with the calcium indicator bis-fura-2. Twitch force-calcium relationships and steady-state force-[Ca(2+)](i) relationships were measured at various muscle lengths at 37 degrees C using potassium induced contractures. The EC(50) significantly decreased with increase in muscle length and maximal active force development significantly increased, while no significant change in the myofilament cooperativity coefficient was found. Phosphoprotein analysis Pro-Q diamond staining as well as phosphorylation specific antibodies revealed increased phosphorylation of tropomyosin, troponin I, and myosin light chain-2 at longer muscle lengths. Specifically, TnI phosphorylation at Ser(22/23) was increased. Since the immediate response is seen virtually instantaneously and post-translational modifications are thought not to occur within such a very short timeframe, we hypothesize that these increases in phosphorylation occur during the slow response. PMID- 20298700 TI - Positive correlations between molecular and morphological rates of evolution. AB - The existence of positive associations between rates of molecular and morphological evolution (calculated from branch lengths of phylogenetic trees reconstructed using molecular and morphological characters, respectively) is important to issues of neutrality in sequence evolution, phylogenetic reconstructions assuming neutrality, and evolutionary genotype-phenotype mapping. Rates correlate positively when including branches leading to extant species (tips). Excluding tips, trends are similar, but statistical significances decrease systematically. This is due to (a) lower statistical power (excluding tips reduces sample sizes), and (b) rates are solely calculated from inaccurately reconstructed character states of extinct ancestral species, and this noise decreases correlation strengths. Correlations between molecular and morphological rates of evolution increase as more morphological characters are included for phylogenetic reconstruction. Sequence lengths apparently affect correlations along similar principles. Analyses of plant phylogenies confirm those from animals: sampling biases decrease correlations between molecular and morphological rates of evolution. Results confirm that genotype and phenotype are linked, and suggest adaptive components for molecular evolution. The discussion stresses the difficulties associated with analyses and conclusions based on data deduced from phylogenetic reconstruction. PMID- 20298701 TI - Evolutionary stability and quasi-stationary strategy in stochastic evolutionary game dynamics. AB - Stochastic evolutionary game dynamics for finite populations has recently been widely explored in the study of evolutionary game theory. It is known from the work of Traulsen et al. [2005. Phys. Rev. Lett. 95, 238701] that the stochastic evolutionary dynamics approaches the deterministic replicator dynamics in the limit of large population size. However, sometimes the limiting behavior predicted by the stochastic evolutionary dynamics is not quite in agreement with the steady-state behavior of the replicator dynamics. This paradox inspired us to give reasonable explanations of the traditional concept of evolutionarily stable strategy (ESS) in the context of finite populations. A quasi-stationary analysis of the stochastic evolutionary game dynamics is put forward in this study and we present a new concept of quasi-stationary strategy (QSS) for large but finite populations. It is shown that the consistency between the QSS and the ESS implies that the long-term behavior of the replicator dynamics can be predicted by the quasi-stationary behavior of the stochastic dynamics. We relate the paradox to the time scales and find that the contradiction occurs only when the fixation time scale is much longer than the quasi-stationary time scale. Our work may shed light on understanding the relationship between the deterministic and stochastic methods of modeling evolutionary game dynamics. PMID- 20298702 TI - Evolution and instability in ring species complexes: an in silico approach to the study of speciation. AB - Ring species are a biological complex that theoretically forms when an ancestral population extends its range around a geographic barrier and, despite low-level gene flow, differentiates until reproductive isolation exists when terminal populations come into secondary contact. Due to their rarity in nature, little is known about the biological factors that promote the formation of ring species. We use evolutionary algorithms operating on two simple computational problems (SAW and K-max) to study the process of speciation under the conditions which may yield ring species. We vary evolutionary parameters to measure their influence on ring species' development and stability over evolutionary time. Using the SAW problem, ring species consistently form, i.e. fertility is negatively correlated with distance (R-values between -0.097 and -0.821, p<0.001), and terminal populations show substantial infertility. However, all SAW simulations demonstrate instability in the complex after sympatric zones are established between terminal populations. Higher mutation rates and larger dispersal/breeding radii promote ring species' formation and stability. Using a problem with a simple fitness landscape, the K-max problem, ring species do not form. Instead, speciation around the ring occurs before ring closure as good genotypes become locally dominant. PMID- 20298703 TI - From heroin epidemics to methamphetamine epidemics: modelling substance abuse in a South African province. AB - The global rise in the use of methamphetamine has been documented to have reached epidemic proportions. Researchers have focussed on the social implications of the epidemic. A typical drug use cycle consists of concealed drugs use after initiation, addiction, treatment-recovery-relapse cycle, whose dynamics are not well understood. The model by White and Comiskey [41], on heroin epidemics, treatment and ODE modelling, is modified to model the dynamics of methamphetamine use in a South African province. The analysis of the model is presented in terms of the methamphetamine epidemic threshold R(0). It is shown that the model has multiple equilibria and using the center manifold theory, the model exhibits the phenomenon of backward bifurcation where a stable drug free equilibrium co-exists with a stable drug persistent equilibrium for a certain defined range of R(0). The stabilities of the model equilibria are ascertained and persistence conditions established. Furthermore, numerical simulations are performed; these include fitting the model to the available data on the number of patients with methamphetamine problems. The implications of the results to drug policy, treatment and prevention are discussed. PMID- 20298704 TI - Dyscravia: voicing substitution dysgraphia. AB - We report a new type of dysgraphia, which we term dyscravia. The main error type in dyscravia is substitution of the target letter with a letter that differs only with respect to the voicing feature, such as writing "coat" for "goat", and "vagd" for "fact". Two Hebrew-speaking individuals with acquired dyscravia are reported, TG, a man aged 31, and BG, a woman aged 66. Both had surface dysgraphia in addition to their dyscravia. To describe dyscravia in detail, and to explore the rate and types of errors made in spelling, we administered tests of writing to dictation, written naming, and oral spelling. In writing to dictation, TG made voicing errors on 38% of the words, and BG made 17% voicing errors. Voicing errors also occurred in nonword writing (43% for TG, 56% for BG). The writing performance and the variables that influenced the participants' spelling, as well as the results of the auditory discrimination and repetition tasks indicated that their dyscravia did not result from a deficit in auditory processing, the graphemic buffer, the phonological output lexicon, the phonological output buffer, or the allographic stage. The locus of the deficit is the phoneme-to grapheme conversion, in a function specialized in the conversion of phonemes' voicing feature into graphemes. Because these participants had surface dysgraphia and were forced to write via the sublexical route, the deficit in voicing was evident in their writing of both words and nonwords. We further examined whether the participants also evinced parallel errors in reading. TG had a selective voicing deficit in writing, and did not show any voicing errors in reading, whereas BG had voicing errors also in the reading of nonwords (i.e., she had dyslegzia in addition to dyscravia). The dissociation TG demonstrated indicated that the voicing feature conversion is separate for reading and writing, and can be impaired selectively in writing. BG's dyslegzia indicates that the grapheme-to phoneme conversion also includes a function that is sensitive to phonological features such as voicing. Thus the main conclusion of this study is that a separate function of voicing feature conversion exists in the phoneme-to-grapheme conversion route, which may be selectively impaired without deficits in other functions of the conversion route, and without a parallel deficit in reading. PMID- 20298705 TI - Non-lethal effects of predators on body growth and health state of juvenile lizards, Psammdromus algirus. AB - Predation risk does not necessarily increase predation rates because prey may be able to behave differentially to cope with higher predation risk. However, antipredatory behaviors may be costly, leading to negative, although non-lethal, effects of predators on prey. We examined in outdoor enclosures whether an experimental increase in predation pressure, which did not increase direct mortality, but forced individuals to increase antipredatory behaviors, may have significant non-lethal effects on body growth and health state of juvenile lizards, Psammodromus algirus. Simulated persistent predator attacks resulted in slower rates of body size growth and body mass gain of juvenile lizards, which may greatly affect their future survival. However, juvenile lizards were able to maintain their initial body condition and immune response regardless of predation risk level. Moreover, our data suggested that experience of lizards with their home range "environment" might allow them to compensate the negative effects of temporal high predation risk on body condition when predation risk subsequently decreased. Finally, juvenile lizards with greater immune responses showed smaller increments in body size, but larger increments in body mass and body condition, at the end of the control treatment. In contrast, there was no relationship between immunity and growth after the experimental treatment. PMID- 20298707 TI - Mild hypohydration induced by exercise in the heat attenuates autonomic thermoregulatory responses to the heat, but not thermal pleasantness in humans. AB - Hypohydration caused by exercise in the heat attenuates autonomic thermoregulation such as sweating and skin blood flow in humans. In contrast, it remains unknown if behavioral thermoregulation is modulated during hypohydration. We assume that thermal unpleasantness could drive the behavioral response, and would also be modulated during hypohydration. Nine healthy young men participated in the present study. Body and skin temperatures were monitored. Ratings of thermal sensation and pleasantness were conducted. After approximately 45 min rest at 27 degrees C, they performed 50-min cycling exercise, which was at the level of 40% of heart rate range at 35 degrees C (hypohydration trial) or at the level of 10% of heart rate range at 23 degrees C (control trial), respectively. Subjects returned to the rest at 27 degrees C, and the ambient temperature was then changed from 22 to 38 degrees C. Body weight decreased by 0.9+/-0.1% immediately after exercise in the hypohydration trial and 0.3+/-0.1% in the control trial. In the cold, no significant difference in thermal sensation or pleasantness was observed between trials. There was no significant difference in thermal pleasantness between trials in the heat, although thermal sensation in the heat (32.5-36 degrees C) was significantly lower in the hypohydration trial than in the control trial. In addition, laser Doppler flow of the skin and sweat rate were attenuated in the heat in the hypohydration trial. These results may indicate that mild hypohydration after exercise in the heat has no influence on behavioral responses to the heat. PMID- 20298706 TI - Corticosteroid and neurosteroid dysregulation in an animal model of autism, BTBR mice. AB - Autism spectrum disorders (ASD) are a constellation of neurodevelopmental disorders associated with disruptions in social, cognitive, and/or motor behaviors. ASD are more prevalent among males than females and characterized by aberrant social and language development, and a dysregulation in stress responding. Levels of progesterone (P(4)) and its metabolite 5alpha-pregnan 3alpha-ol-20-one (3alpha,5alpha-THP) are higher and more variable in females compared to males. 3alpha,5alpha-THP is also a neurosteroid, which can be rapidly produced de novo in the brain, independent of peripheral gland secretion, and can exert homeostatic effects to modulate stress-responding. An inbred mouse strain that has demonstrated an ASD-like behavioral and neuroendocrine phenotype is BTBR T +tf/J (BTBR). BTBR mice have deficits in cognitive and social behaviors and have high circulating levels of the stress hormone, corticosterone. We hypothesized that central 3alpha,5alpha-THP levels would be different among BTBR mice compared to mice on a similar background C57BL/6J (C57/J) and 129S1/SvlmJ (129S1). Tissues were collected from BTBR, C57/J and 129S1 male mice and levels of corticosterone, P(4), and 3alpha,5alpha-THP in plasma and in the hypothalamus, midbrain, hippocampus, and cerebellum were measured by radioimmunoassay. Circulating levels of corticosterone, P(4), and 3alpha,5alpha-THP were significantly higher among BTBR, than C57/J and 129S1, mice. Levels of P(4) in the cerebellum were significantly higher than other brain regions among all mouse strains. Levels of 3alpha,5alpha-THP in the hypothalamus of BTBR mice were significantly higher compared to C57/J and 129S1 mice. These findings suggest that neuroendocrine dysregulation among BTBR mice extends to 3alpha,5alpha-THP. PMID- 20298710 TI - Metarhizium anisopliae enzymes and toxins. AB - Entomopathogenic fungi are both a feasible system for the control of insect pests in agriculture with a growing market and an important model for studies of host pathogen interaction. In the last ten years the actual use of fungi, mainly Metarhizium anisopliae and Beauveria bassiana, is increasing reaching commercial scale in Countries like Brazil, China and Mexico among others. At the same time important progress has occurred in the understanding of the molecular aspects of the pathogenesis and in the development of tools to validate putative virulence factors by the construction of over-expressing and knock-out strains. This wealth of knowledge is helping to access more efficient strains from the biodiversity and to optimize formulation for large scale use of this efficient, economic and environmental safer form of insect plague control. Here we focus some of the progress accumulated specially in M. anisopliae and give an overview of the host infection process. PMID- 20298708 TI - Reinforcing efficacy of fat, as assessed by progressive ratio responding, depends upon availability not amount consumed. AB - Intermittent limited access to an optional source of dietary fat can induce binge type behavior in rats. However, the ability of such access to alter the reinforcing efficacy of fat has not been clearly demonstrated. In this study, performance under progressive ratio one (PR1) and three (PR3) schedules of shortening (fat) reinforcement was assessed in non-food deprived rats (n=15/group). One group of rats had intermittent access to a dietary fat option (INT, 1-hour shortening access in the home cage each Monday, Wednesday, and Friday), whereas the other group had daily access to the fat option (D, 1-hour shortening access daily). Chow and water were continuously available. After five weeks, the INT group consumed more shortening during the 1-hour access period than did the D group. Rats were then trained to lever press for a solid shortening reinforcer (0.1 gm). INT rats earned significantly more reinforcers than did D rats under PR1, but not under PR3. Subgroups of INT and D rats (n=7 each) were matched on the amount of shortening consumed in the home cage during week five of the protocol and the PR data were reanalyzed. The INT subgroup earned significantly more reinforcers than the D subgroup did under PR1, but not PR3. These results demonstrate that: (1) intermittent access to shortening in the home cage, but not the amount consumed during the access period (i.e. bingeing), increases the reinforcing efficacy of solid shortening; and (2) the type of PR schedule is critical in delineating differences between the groups. PMID- 20298709 TI - Cr(VI) induces mitochondrial-mediated and caspase-dependent apoptosis through reactive oxygen species-mediated p53 activation in JB6 Cl41 cells. AB - Cr(VI) compounds are known to cause serious toxic and carcinogenic effects. Cr(VI) exposure can lead to a severe damage to the skin, but the mechanisms involved in the Cr(VI)-mediated toxicity in the skin are unclear. The present study examined whether Cr(VI) induces cell death by apoptosis or necrosis using mouse skin epidermal cell line, JB6 Cl41 cells. We also investigated the cellular mechanisms of Cr(VI)-induced cell death. This study showed that Cr(VI) induced apoptotic cell death in a dose-dependent manner, as demonstrated by the appearance of cell shrinkage, the migration of cells into the sub-G1 phase, the increase of Annexin V positively stained cells, and the formation of nuclear DNA ladders. Cr(VI) treatment resulted in the increases of mitochondrial membrane depolarization and caspases activation. Electron spin resonance (ESR) and fluorescence analysis revealed that Cr(VI) increased intracellular levels of reactive oxygen species (ROS) such as hydrogen peroxide and superoxide anion radical in dose-dependent manner. Blockage of p53 by si-RNA transfection suppressed mitochondrial changes of Bcl-2 family composition, mitochondrial membrane depolarization, caspase activation and PARP cleavage, leading to the inhibition of Cr(VI)-induced apoptosis. Further, catalase treatment prevented p53 phosphorylation stimulated by Cr(VI) with the concomitant inhibition of caspase activation. These results suggest that Cr(VI) induced a mitochondrial-mediated and caspase-dependent apoptosis in skin epidermal cells through activation of p53, which are mainly mediated by reactive oxidants generated by the chemical. PMID- 20298711 TI - Production and characterization of monoclonal antibodies against vaginolysin: mapping of a region critical for its cytolytic activity. AB - Vaginolysin (VLY) is a protein toxin released by Gardnerella vaginalis. VLY belongs to the group of cholesterol-dependent cytolysins (CDCs). We have generated a panel of novel monoclonal antibodies (MAbs) against VLY. For the generation of MAbs, we have used recombinant VLY expressed in Escherichia coli. The functional activity of recombinant VLY was confirmed by an in vitro hemolytic assay using human erythrocytes. The MAbs raised against recombinant VLY were reactive with VLY from G. vaginalis both by Western blot and ELISA. The cross reactivity of MAbs with other CDCs was investigated. For this purpose, recombinant cytolysins perfringolysin, listeriolysin, intermedilysin, pneumolysin and streptolysin were expressed in E. coli. The MAbs were specific exclusively to VLY and did not react with other CDCs. All MAbs were studied for the ability to neutralize hemolytic activity of VLY in vitro and several neutralizing MAbs were identified. The MAb produced by clone 9B4 showed the most potent neutralizing activity. The epitope for this MAb was localized near the N-terminus of VLY, between amino acid (aa) residues 112 and 268. The region recognized by the neutralizing MAb 9B4 includes the conserved motif (VAARMQYD, aa 189-196) supposed to be involved in VLY oligomerization. Selected MAbs were employed to develop a sandwich ELISA for VLY quantification. The MAb-based immunoassay was suitable for the detection of VLY in the cultures of G. vaginalis. In conclusion, the MAbs described in the current study may be useful for structural and functional studies of VLY as well as immunodetection of VLY in biological specimens. PMID- 20298712 TI - The accuracy of metric judgements: perception of surface normal. AB - Observers adjusted a probe (a short rod) to appear normal to a planar surface slanted in depth. In Experiment 1, observers (N=12) performed this metric task in two conditions: with reduced cues to calibration of binocular viewing parameters and with full cues. The results provided evidence for the use of an internal working metric in metric tasks because they confirm predictions that (i) errors should be largely systematic and accounted for by assuming an inaccurate working metric and (ii) this metric should be consistent with miscalibration of relevant viewing parameters. The data support the prediction that performance errors decrease in a manner consistent with improved binocular calibration, when better cues to relevant viewing parameters are provided. We performed two additional control experiments as further tests of the binocular miscalibration account, to determine whether performance in Experiment 1 could be explained instead by the use of monocular cues. We found that monocular performance was significantly poorer than binocular performance in reduced-cue conditions (Experiment 2) and full-cue conditions (Experiment 3). These control experiments provide confirmation that binocular cues contribute to performance in the full-cue conditions of Experiment 1, and that disparity was the only effective cue to slant in reduced-cue conditions. PMID- 20298713 TI - A simple model of the vertical-horizontal illusion. AB - In spite of being one of the most elementary visual effects, the vertical horizontal illusion is still poorly understood. We provide here a simple quantitative model to describe the overestimation of the vertical segment relative to the horizontal one. The model also includes a necessary factor related to the effect of bisecting a line on the under-estimation of its length. These two factors, orientation anisotropy and length bisection, provide a very good account of various configurations of the illusion when the stimulus looks like a 'T', an 'L', or a '+'-sign, and for different stimulus orientations. The orientation anisotropy bias is on average 6% while the length bisection bias amounts to about 16%. In addition, when uncertainty about line estimation is included, new predictions on the sensitivity of different configurations are obtained and confirmed. In particular, we find that the '+'-sign figure suffers from a loss of sensitivity in comparing their vertical and horizontal segments when compared to the 'L'-figure. This difference can only be accounted for by a late-noise model where uncertainty is at the decision stage rather than on the image measurements. PMID- 20298714 TI - Methamphetamine-induced stereotypy correlates negatively with patch-enhanced prodynorphin and arc mRNA expression in the rat caudate putamen: the role of mu opioid receptor activation. AB - Amphetamines induce stereotypy, which correlates with patch-enhanced c-Fos expression the patch compartment of caudate putamen (CPu). Methamphetamine (METH) treatment also induces patch-enhanced expression of prodynorphin (PD), arc and zif/268 in the CPu. Whether patch-enhanced activation of any of these genes correlates with METH-induced stereotypy is unknown, and the factors that contribute to this pattern of expression are poorly understood. Activation of mu opioid receptors, which are expressed by the neurons of the patch compartment, may underlie METH-induced patch-enhanced gene expression and stereotypy. The current study examined whether striatal mu opioid receptor blockade altered METH induced stereotypy and patch-enhanced gene expression, and if there was a correlation between the two responses. Animals were intrastriatally infused with the mu antagonist CTAP (10 microg/microl), treated with METH (7.5 mg/kg, s.c.), placed in activity chambers for 3h, and then sacrificed. CTAP pretreatment attenuated METH-induced increases in PD, arc and zif/268 mRNA expression and significantly reduced METH-induced stereotypy. Patch-enhanced PD and arc mRNA expression in the dorsolateral CPu correlated negatively with METH-induced stereotypy. These data indicate that mu opioid receptor activation contributes to METH-induced gene expression in the CPu and stereotypy, and that patch-enhanced PD and arc expression may be a homeostatic response to METH treatment. PMID- 20298716 TI - Automatic auditory intelligence: an expression of the sensory-cognitive core of cognitive processes. AB - In this article, we present a new view on the nature of cognitive processes suggesting that there is a common core, viz., automatic sensory-cognitive processes that form the basis for higher-order cognitive processes. It has been shown that automatic sensory-cognitive processes are shared by humans and various other species and occur at different developmental stages and even in different states of consciousness. This evidence, based on the automatic electrophysiological change-detection response mismatch negativity (MMN), its magnetoencephalographic equivalent MMNm, and behavioral data, indicates that in audition surprisingly complex processes occur automatically and mainly in the sensory-specific cortical regions. These processes include, e.g. stimulus anticipation and extrapolation, sequential stimulus-rule extraction, and pattern and pitch-interval encoding. Furthermore, these complex perceptual-cognitive processes, first found in waking adults, occur similarly even in sleeping newborns, anesthetized animals, and deeply sedated adult humans, suggesting that they form the common perceptual-cognitive core of cognitive processes in general. Although the present evidence originates mainly from the auditory modality, it is likely that analogous evidence could be obtained from other sensory modalities when measures corresponding to those used in the study of the auditory modality become available. PMID- 20298715 TI - Pharmacological characterization of GPR55, a putative cannabinoid receptor. AB - GPR55 has recently attracted much attention as another member of the cannabinoid family, potentially explaining physiological effects that are non-CB1/CB2 mediated. However, the data gathered so far are conflicting with respect to its pharmacology. We review the primary literature to date on GPR55, describing its discovery, structure, pharmacology and potential physiological functions. The CB1 receptor antagonist/inverse agonist AM251 has been shown to be a GPR55 agonist in all reports in which it was evaluated, as has the lysophospholipid, lysophosphatidylinositol (LPI). Whether GPR55 responds to the endocannabinoid ligands anandamide and 2-arachidonylglycerol and the phytocannabinoids, delta-9 tetrahydrocannabidiol and cannabidiol, is cell type and tissue-dependent. GPR55 has been shown to utilize G(q), G(12), or G(13) for signal transduction; RhoA and phospholipase C are activated. Experiments with mice in which GPR55 has been inactivated reveal a role for this receptor in neuropathic and inflammatory pain as well as in bone physiology. Thus delineating the pharmacology of this receptor and the discovery of selective agonists and antagonists merits further study and could lead to new therapeutics. PMID- 20298717 TI - Time-shift denoising source separation. AB - I present a new method for removing unwanted components from neurophysiological recordings such as magnetoencephalography (MEG), electroencephalography (EEG), or multichannel electrophysiological or optical recordings. A spatiotemporal filter is designed to partition recorded activity into noise and signal components, and the latter are projected back to sensor space to obtain clean data. To obtain the required filter, the original data waveforms are delayed by a series of time delays, and linear combinations are formed based on a criterion such as reproducibility over stimulus repetitions. The time shifts allow the algorithm to automatically synthesize multichannel finite impulse response filters, improving denoising capabilities over static spatial filtering methods. The method is illustrated with synthetic data and real data from several biomagnetometers, for which the raw signal-to-noise ratio of stimulus-evoked components was unfavorable. With this technique, components with power ratios relative to noise as small as 1 part per million can be retrieved. PMID- 20298718 TI - Stochastic estimation of human arm impedance under nonlinear friction in robot joints: a model study. AB - The basic assumption of stochastic human arm impedance estimation methods is that the human arm and robot behave linearly for small perturbations. In the present work, we have identified the degree of influence of nonlinear friction in robot joints to the stochastic human arm impedance estimation. Internal model based impedance control (IMBIC) is then proposed as a means to make the estimation accurate by compensating for the nonlinear friction. From simulations with a nonlinear Lugre friction model, it is observed that the reliability and accuracy of the estimation are severely degraded with nonlinear friction: below 2 Hz, multiple and partial coherence functions are far less than unity; estimated magnitudes and phases are severely deviated from that of a real human arm throughout the frequency range of interest; and the accuracy is not enhanced with an increase of magnitude of the force perturbations. In contrast, the combined use of stochastic estimation and IMBIC provides with accurate estimation results even with large friction: the multiple coherence functions are larger than 0.9 throughout the frequency range of interest and the estimated magnitudes and phases are well matched with that of a real human arm. Furthermore, the performance of suggested method is independent of human arm and robot posture, and human arm impedance. Therefore, the IMBIC will be useful in measuring human arm impedance with conventional robot, as well as in designing a spatial impedance measuring robot, which requires gearing. PMID- 20298719 TI - A self-referencing glutamate biosensor for measuring real time neuronal glutamate flux. AB - Quantification of neurotransmitter transport dynamics is hindered by a lack of sufficient tools to directly monitor bioactive flux under physiological conditions. Traditional techniques for studying neurotransmitter release/uptake require inferences from non-selective electrical recordings, are invasive/destructive, and/or suffer from poor temporal resolution. Recent advances in electrochemical biosensors have enhanced in vitro and in vivo detection of neurotransmitter concentration under physiological/pathophysiological conditions. The use of enzymatic biosensors with performance enhancing materials (e.g., carbon nanotubes) has been a major focus for many of these advances. However, these techniques are not used as mainstream neuroscience research tools, due to relatively low sensitivity, excessive drift/noise, low signal-to-noise ratio, and inability to quantify rapid neurochemical kinetics during synaptic transmission. A sensing technique known as self-referencing overcomes many of these problems, and allows non-invasive quantification of biophysical transport. This work presents a self-referencing CNT modified glutamate oxidase biosensor for monitoring glutamate flux near neural/neuronal cells. Concentration of basal glutamate was similar to other in vivo and in vitro measurements. The biosensor was used in self-referencing (oscillating) mode to measure net glutamate flux near neural cells during electrical stimulation. Prior to stimulation, the average influx was 33.9+/-6.4 fmol cm(-2)s(-1)). Glutamate efflux took place immediately following stimulation, and was always followed by uptake in the 50-150 fmol cm(-2)s(-1) range. Uptake was inhibited using threo-beta-benzyloxyaspartate, and average surface flux in replicate cells (1.1+/-7.4 fmol cm(-2)s(-1)) was significantly lower than uninhibited cells. The technique is extremely valuable for studying neuropathological conditions related to neurotransmission under dynamic physiological conditions. PMID- 20298720 TI - Seroma fluid subsequent to axillary lymph node dissection for breast cancer derives from an accumulation of afferent lymph. AB - Seroma is a frequent complication of breast cancer surgery, the etiology of which remains indefinite. It represents a subcutaneous accumulation of fluid frequently reported after surgical procedures such as axillary lymph node dissection. Despite previous studies have associated seroma fluid to an inflammatory exudate, the surgical removal of draining lymph nodes may indicate that seroma might not represent a mere exudate but rather an accrual of lymph drained from tributary tissues. To verify this hypothesis, seromas were collected at different intervals of time in patients operated upon for axillary lymph node removal. Fluids were analyzed in details by flow cytometry and biochemical assays for their cellular content and for their molecular features and relevant cytokine content. Lymphocytes and other peculiar blood mononuclear cells were present, while erythrocytes, platelets and granulocytes were absent or extremely rare. The protein concentration resulted lower (median 64%) than in peripheral blood. However, specific proteins related to locoregional tissues resulted highly concentrated (e.g. up to 500% for ferritin and 300% for lactate deydrogenase and exclusive presence of interleukin-6) whereas all enzymes and proteins synthesized in the liver or other organs (e.g. alkaline phosphatase, ALT, gammaGT, prealbumin, transferrin, ceruloplasmin, C3 and C4, alpha2 macroglobulin from liver; apolipoproteins from liver and gut; amylase and lipase from pancreas) were represented in reduced concentrations, thus ruling out that seroma proteins derive directly from blood serum. As a whole, this comprehensive cytological and molecular analysis provided evidences that seroma is constituted by serum ultrafiltrated-derived extracellular fluid of regions located upstream of removed lymph nodes. This fluid is then enriched by proteins and cells collected in the drained regions. Remarkably, seroma fluids collected in the same patient at different time points (up to 50 days following surgery) displayed similar biochemical features, clearly indicating that fluid composition was not significantly affected by post-surgical locoregional flogosis. Finally, the period of seroma formation indicates that lymph accumulates in the axillary region during the interval of time needed for afferent lymphatic vessels to re anastomose with the efferent ducts. Therefore, seroma fluid represents a font of biological material suitable for investigating the biology of breast cancer, healing tissues and lymph. PMID- 20298721 TI - Conservation of HHV-6 DNA polymerase processivity factor sequence and predicted structure suggests it as a target for antiviral development. AB - The replication of human herpesvirus-6 (HHV-6) DNA is catalyzed by the viral DNA polymerase pU38 and the processivity factor pU27 which stabilizes the enzyme on the DNA template. The genetic polymorphism of pU27 among 46 clinical strains of HHV-6 variant A or B and four strains resistant to antivirals was investigated. Overall, 28 amino acid changes (7.6%) and a two-amino acid deletion were identified among the 368 residues of pU27, when using the U1102 (variant A) sequence as the reference. Eleven amino acid changes (3.0%) specifically differentiated both variants. The median intravariant amino acid variability was 1.2% and 0.3% for A and B, respectively. Except for a single change, the pU27 sequence of multi-drug resistant HHV-6 strains was also conserved. Structural models of pU27 for variants A and B were derived from that of the human cytomegalovirus homologue pUL44, and showed either identical or very similar residues in the regions interacting with viral DNA polymerase and viral DNA molecule. As pU27 is both highly conserved and essential for viral replication, it might constitute an interesting target for antiviral chemotherapy. PMID- 20298723 TI - Development and refinement of a high-efficiency gene-targeting system for Aspergillus flavus. AB - An efficient gene-targeting system based on impairment of the nonhomologous end joining pathway and the orotidine monophosphate decarboxylase gene (pyrG) in Aspergillus flavus was established. It was achieved by replacing the ku70 gene with the Aspergillus oryzae pyrithiamine resistance (ptr) gene and by inserting the Aspergillus parasiticus cypA gene into the pyrG locus. The utility of this system was demonstrated by disruption of nine candidate genes for conidial pigment biosynthesis. The gene-targeting frequencies ranged from 80 to 100%. Two linked genes on chromosome 4, wA and olgA, were confirmed to be involved in pigment formation. In contrast to the parental strain which produced yellowish green conidia, the knockout mutants produced white and olive-green conidia, respectively. The system was further refined by restoring the pyrithiamine sensitivity and uracil auxotrophy in the A. flavus transformation recipient with an engineered pyrG marker. The improvement allowed gene manipulation using the reusable pyrG marker as shown by the restoration of laeA-mediated aflatoxin production in an A. flavus laeA-deleted mutant. PMID- 20298722 TI - Contributions of the amygdala central nucleus and ventrolateral periaqueductal grey to freezing and instrumental suppression in Pavlovian fear conditioning. AB - In Pavlovian fear conditioning animals receive pairings of a neutral cue and an aversive stimulus such as an electric foot-shock. Through such pairings, the cue will come to elicit a central state of fear that produces a variety of autonomic and behavioral responses, among which are conditioned freezing and suppression of instrumental responding, termed conditioned suppression. The central nucleus of the amygdala (CeA) and the ventrolateral periaqueductal grey (vlPAG) has been strongly implicated in the acquisition and expression of conditioned fear. However, previous work suggests different roles for the CeA and vlPAG in fear learning maybe revealed when fear is assessed with conditioned freezing or conditioned suppression. To further explore this possibility we gave rats selective lesions of either the CeA or vlPAG and trained them in Pavlovian first order fear conditioning as well as Pavlovian second-order fear conditioning. We concurrently assessed the acquisition of conditioned freezing and conditioned suppression. We found that vlPAG and CeA lesions impaired both first- and second order conditioned freezing. VlPAG lesions did not impair, and CeA lesions only transiently impaired, first-order conditioned suppression. However, both vlPAG and CeA lesions impaired second-order conditioned suppression. These results suggest that the CeA and vlPAG are critically important to expressing fear through conditioned freezing but play different and less critical roles in expressing fear through conditioned suppression. PMID- 20298724 TI - Rapid detection of Pseudomonas aeruginosa in mouse feces by colorimetric loop mediated isothermal amplification. AB - A colorimetric loop-mediated isothermal amplification (LAMP) assay with hydroxy naphthol blue was designed to amplify a region in the outer membrane lipoprotein (oprL) gene of Pseudomonas aeruginosa. The LAMP assay showed 100% specificity for the serogroup and other bacteria, and the sensitivity was 10-fold higher than that of the PCR assays. The LAMP assay could detect P. aeruginosa inoculated in mouse feces at 130 colony-forming units (CFU)/0.1g feces (3.25 CFU/reaction). The assay was completed within 2h from DNA extraction. In a field trial, the LAMP assay revealed that none of the 27 samples was obtained from 2 specific pathogen free (SPF) mouse facilities that were monitoring infection with P. aeruginosa; 1 out of 12 samples from an SPF mouse facility that was not monitoring infection with P. aeruginosa and 2 out of 7 samples from a conventional mouse facility were positive for P. aeruginosa. In contrast, P. aeruginosa was not detected in any of the samples by a conventional culture assay. Thus, this colorimetric LAMP assay is a simple and rapid method for P. aeruginosa detection. PMID- 20298725 TI - Strain improvement of the pentose-fermenting yeast Pichia stipitis by genome shuffling. AB - Genome shuffling based on cross mating was used to improve the tolerance of the pentose-fermenting yeast Pichia stipitis towards hardwood spent sulphite liquor (HW SSL). Six UV-induced mutants of P. stipitis were used as the starting strains, and they were subjected to 4 rounds of genome shuffling. After each round, improved strains were selected based on their growth on HW SSL gradient plates. Mutant libraries were established after each round and these improved mutant strains served as the starting pool for the next round of shuffling. Apparent tolerance to HW SSL on the gradient plate increased progressively with each round of shuffling up to 4 rounds. Selected improved mutants were further tested for tolerance to liquid HW SSL. After 4 rounds of shuffling, 4 mutants, two from the third round (designated as GS301 and GS302) and two from the fourth round (designated as GS401 and GS402), were selected that could grow in 80% (v/v) HW SSL. GS301 and GS302 grew also in 85% (v/v) HW SSL. GS301 was viable in 90% (v/v) HW SSL, although no increase in cell number was seen. The P. stipitis wild type strain (WT) could not grow on HW SSL unless it was diluted to 65% (v/v) or lower. Genome-shuffled strains with improved tolerance to HW SSL retained their fermentation ability. Fermentation performance of GS301 and GS302, the 2 strains that exhibited the best tolerance to liquid HW SSL, was assessed in defined media and in HW SSL. Both strains utilized 4% (w/v) of xylose or glucose more efficiently and produced more ethanol than the WT. They also utilized 4% (w/v) of mannose or galactose and produced ethanol to the same extent as the WT. GS301 and GS302 were able to produce low levels of ethanol in undiluted HW SSL. PMID- 20298726 TI - Simple and rapid method for detection of nitrate reductase activity of Mycobacterium tuberculosis and Mycobacterium canettii grown in the Bactec MGIT960 system. AB - Mycobacterium tuberculosis reduces nitrate very strongly as compared to Mycobacterium bovis and M. bovis BCG. Nitrate reductase, in conjunction with niacin accumulation, constitutes one of the major biochemical tests used in clinical microbiology laboratories to differentiate M. tuberculosis from other members of the M. tuberculosis complex, as well as nontuberculous Mycobacteria. Determination of nitrate reductase activity is currently performed using cultures grown on solid media with a slow detection time and the need for large quantities of bacilli, as otherwise the test is not reliable. Hereby, we propose a nitrate reduction test coupled to Bactec MGIT960 system as a simple, rapid and economic method with a total gain of time of about 3 to 4weeks over the conventional solid medium. In our study, almost all the M. tuberculosis and Mycobacterium canettii strains gave a strongly positive nitrate reductase result within 1day of positive detection by the MGIT960 system. In contrast, M. bovis, M. bovis BCG and M. africanum strains remained negative even after 14days of incubation. The possibility to detect nitrate reductase within 1 to 3days of a positive culture using MGIT960 opens new perspectives with the possibility of confirming M. tuberculosis - starting directly from pathological specimens. PMID- 20298727 TI - Swab transport in Amies gel followed by frozen storage in skim milk tryptone glucose glycerol broth (STGGB) for studies of respiratory bacterial pathogens. AB - Nasopharyngeal carriage studies are needed to monitor changes in important bacterial pathogens in response to vaccination and antibiotics. Commercial swab transport followed by transfer to skim milk tryptone glucose glycerol broth for frozen storage is an option for studies of Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis. PMID- 20298728 TI - Scopolamine-induced learning impairment reversed by physostigmine in zebrafish. AB - In this study, the effects of scopolamine, an acetylcholine muscarinic receptor antagonist, and physostigmine, an acetylcholinesterase inhibitor, on the learning ability and memory of zebrafish were evaluated using a passive avoidance response test. The zebrafish were trained to stay in a dark compartment to avoid a weight dropping into an acryl shuttle chamber with a central sliding door. The crossing time was increased significantly, from 30.7+/-40.8s to 179.3+/-27.3s in the training session and 179.9+/-28.0s in the test session carried out 2h later in the controls. When treatment with 200 microM scopolamine was administered for 1h prior to the training session, the crossing time did not increase. The scopolamine-induced learning deficit was ameliorated by pretreatment with 20 microM physostigmine for 1h prior to scopolamine treatment; the crossing time was similarly increased, as shown with the controls (60.9+/-11.5s, 130.9+/-27.5s, and 183.4+/-26.6s in the training session and 108.1+/-23.9s in the test session). When scopolamine treatment was administered after the training session, the crossing time in the test session was reduced significantly as compared to that noted in the third trial of the training session, which was also ameliorated by physostigmine pretreatment. These results show that scopolamine impairs both the acquisition of passive avoidance response and retention of the learned response, and that physostigmine rescues the amnesic effects of scopolamine in zebrafish. PMID- 20298730 TI - Restrained eaters show enhanced automatic approach tendencies towards food. AB - Although restrained eaters intend to limit their caloric intake, they nevertheless frequently fail and indulge in exactly the foods they want to avoid. Because automatic food-relevant approach tendencies and affective associations may both (independently) contribute to the dysregulation of food intake, the present study was designed to investigate the importance of both processes in relation to high-fat and low-fat food in restrained and unrestrained eaters. Both restrained and unrestrained eaters demonstrated stronger automatic liking associations with high-fat food than with low-fat food items, whereas a similar pattern was absent in their self-reports of liking food. Interestingly, specifically restrained eaters also displayed relatively strong automatic approach tendencies. These results appear to be consistent with the incentive sensitization theory (Robinson & Berridge, 2001), as overeating seems not so much to be characterized by enhanced liking of food but by stronger automatic approach tendencies towards food. PMID- 20298729 TI - Silk-based delivery systems of bioactive molecules. AB - Silks are biodegradable, biocompatible, self-assembling proteins that can also be tailored via genetic engineering to contain specific chemical features, offering utility for drug and gene delivery. Silkworm silk has been used in biomedical sutures for decades and has recently achieved Food and Drug Administration approval for expanded biomaterials device utility. With the diversity and control of size, structure and chemistry, modified or recombinant silk proteins can be designed and utilized in various biomedical application, such as for the delivery of bioactive molecules. This review focuses on the biosynthesis and applications of silk-based multi-block copolymer systems and related silk protein drug delivery systems. The utility of these systems for the delivery of small molecule drugs, proteins and genes is reviewed. PMID- 20298732 TI - Maintenance electroconvulsive therapy in autistic catatonia: a case series review. AB - The usage of electroconvulsive therapy for the acute resolution of catatonia in autistic children and adults is a novel area that has received increased attention over the past few years. Reported length of the acute ECT course varies among these patients, and there is no current literature on maintenance ECT in autism. The maintenance ECT courses of three patients with autism who developed catatonia are presented. Clinical, research, legal, and administrative implications for ECT treatment in this special population are discussed. PMID- 20298731 TI - Th1 and Th17 immunocompetence in humanized NOD/SCID/IL2rgammanull mice. AB - We evaluated the immunocompetence of human T cells in humanized NOD-SCID interleukin (IL)-2r-gamma-null (hu-NSG) mice bearing a human thymic organoid, after multilineage reconstitution with isogeneic human leukocytes. Delayed type hypersensitivity (DTH) response was assessed by a direct footpad challenge of the immunized hu-NSG host, or by transfer of splenocytes from immunized hu-NSG, along with antigen, into footpads of C.B-17 scid mice (trans vivo [tv] DTH). Both methods revealed cellular immunity to tetanus toxoid (TT) or collagen type V (ColV). Immunohistochemical analysis of the swollen footpads revealed infiltration of human CD45(+) cells, including CD3(+) T cells, CD68(+) macrophages, and murine Ly6G(+) neutrophils. We observed a significant correlation between the percentage of circulating human CD4(+) cells and the direct DTH swelling response to TT. The tvDTH response to TT was inhibited by anti-interferon-gamma, whereas the tvDTH response to collagen V was inhibited by anti-IL-17 antibody, mimicking the cytokine bias of adult human T cells to these antigens. hu-NSG mice were also capable of mounting a B-cell response (primarily IgM) to TT antigen. The activation of either Th1- or Th17-dependent cellular immune response supports the utility of hu-NSG mice as a surrogate model of allograft rejection and autoimmunity. PMID- 20298733 TI - Quetiapine in the treatment of refractory irritable bowel syndrome: a case report. PMID- 20298734 TI - Quetiapine as add-on treatment for bipolar I disorder with comorbid compulsive buying and physical exercise addiction. PMID- 20298735 TI - Probable risperidone-induced tardive "writer's dystonia". PMID- 20298736 TI - Manic switch and serotonin syndrome induced by augmentation of paroxetine with methylphenidate in a patient with major depression. PMID- 20298737 TI - Aripiprazole augmentation for the treatment of an adolescent with posttraumatic stress disorder. PMID- 20298738 TI - Effect of chlorhexidine incorporation into a self-etching primer on dentine bond strength of a luting cement. AB - OBJECTIVES: This study investigated the effect of incorporating chlorhexidine in a self-etching primer on the bond strength of an adhesive resin cement to dentine and on antibacterial activity. METHODS: Experimental self-etching primers were prepared by adding chlorhexidine (CHX) diacetate to ED primer 2.0 (Kuraray Medical Inc.) to obtain chlorhexidine concentrations of 1.0 wt% and 2.0 wt%. Human occlusal dentine surfaces were conditioned for 30 s using the experimental primers or pure ED primer. Composite blocks were luted using Panavia F 2.0 (Kuraray Medical Inc.). After storage in water for 24 h, the bonded teeth were sectioned into 0.9 mm x 0.9 mm beams and stressed to failure in tension to examine microtensile bond strength (microTBS). Fractured surfaces were examined with a field-emission scanning electron microscopy (FE-SEM). The morphology of dentine surfaces that were conditioned with each primer was also observed under FE-SEM. An agar diffusion test was performed to examine the antibacterial effect of each primer against Streptococcus mutans and Enterococcus faecalis. RESULTS: Addition of chlorhexidine to the primer had significant effects (p<0.001) on microTBS and antibacterial effect. No significant difference in microTBS was found between the groups that contained 0% and 1% chlorhexidine in the primer (p=0.095). Conversely, the group that contained 2% chlorhexidine showed significantly lower microTBS and pronounced cohesive failures within the thin layer of the primer. CONCLUSIONS: Incorporation of chlorhexidine into ED primer 2.0 showed significant antibacterial activities. Conditioning with the 1% chlorhexidine-containing primer had no adverse effect on microTBS. PMID- 20298739 TI - A structure-activity study to identify novel and efficient substrates of the human semicarbazide-sensitive amine oxidase/VAP-1 enzyme. AB - Kinetic studies were performed with various alkanamines as "substrate probes" of the properties of the active site of the human semicarbazide-sensitive amine oxidase/vascular adhesion protein-1 (SSAO/VAP-1). We found that the enzyme substrate recognition step is mainly controlled by apolar interactions and that a "good" substrate has a molecular structure containing a long aliphatic chain and a second positive charge at a distance greater than 12 A from the reactive amino group. In this context, we identified a novel substrate for the human SSAO/VAP-1, 1,12-diaminododecane (DIADO), which is characterised by the highest catalytic efficiency reported to date in comparison to the prototypic substrate benzylamine. Computational docking studies revealed the structural basis of this behaviour, highlighting the key role played by Lys393 in hindering substrate docking. Maximum SSAO/VAP-1 activity is reached at relatively low concentrations of DIADO (10-30 microM), and, in these conditions, it has good selectivity: it is a good substrate of SSAO/VAP-1 but not of human adipocyte monoamine oxidases or pig kidney diamine oxidase. From these findings, it appears that DIADO can be used as a new substrate for human SSAO/VAP-1 to elicit glucose transport into adipocytes, and may consequently have potential pharmacological applications in the design of anti-diabetic agents. PMID- 20298740 TI - Compensatory effects of emotion avoidance in adult development. AB - Although compensatory strategies can offset regulatory losses that occur in later adulthood, they often break down under conditions of over-activation. Two emotion regulation tasks examined compensatory effects related to attachment classification (AC). Study 1 examined emotional Stroop performance in young (17 39) and old adults (60-89). Among the elder, participants with dismissing AC showed increased response times (RTs) for anger and fear words, whereas participants with secure AC showed increased RTs for joy words. Participants with anxious AC responded slowest overall. In Study 2, heart rate (HR) was monitored while adult (25-82) mother-daughter pairs discussed three emotion events (conflict, neutral, happy). During conflict discussion, older dismissing women had highest initial HR and slowest recovery, whereas anxious older women had lowest initial HR and fastest recovery. Results suggest that in old age protective functions of dismissing AC break down under over-activation, whereas anxious AC may serve a protective role. PMID- 20298741 TI - Allocation of attention to self-name and self-face: An ERP study. AB - Self-related information, due to its high social/adaptive value, seems to have a preferential access to our attentional resources (cf. the cocktail party effect). However, it remains uncertain whether this attention preference is the same for different kinds of self-related cues. In this ERP study we showed that self-name and self-face when compared with other names and faces, produced very similar patterns of behavioral and neural responses, i.e., shorter reaction times (RTs) and enhanced P300. The processing of the two self-related cues did not differ between each other, neither in RTs nor in P300 responses. In fact, the amplitudes of P300 to self-name and self-face were correlated. These results suggest that the adaptive value of different kinds of self-related cues tends to be equal and they engage attention resources to a similar extent. PMID- 20298742 TI - A novel fluorescent-based assay reveals that thrombopoietin signaling and Bcl X(L) influence, respectively, platelet and erythrocyte lifespans. AB - OBJECTIVE: The factors determining platelet and erythrocyte lifespan are not completely understood, despite extensive study. The lack of success may be attributed to the methods used to measure lifespan kinetics, all of which require processing of cells prior to analysis, and the inconsistent and potentially inappropriate use of mathematical models for data analysis. The aims of this study were to establish an in vivo platelet and erythrocyte labeling method using carboxyfluorescein diacetate succinimidyl ester (CFSE), determine the most appropriate mathematical model for lifespan analysis, and apply both to the study of factors that control platelet and erythrocyte lifespans. MATERIALS AND METHODS: Control, c-mpl knockout (KO), and Bcl-X(L) mutant mice were injected with CFSE and platelet and erythrocyte fluorescence followed over time. Datasets were analyzed using linear, exponential, multiple-hit, and lognormal mathematical models. RESULTS: In vivo CFSE labeling of platelets and erythrocytes requires no postcollection processing, proved stable, nontoxic, nonimmunogenic, and the lifespans were highly reproducible. Mathematical modeling revealed the lognormal model gave a robust fit to control and extreme datasets when either extrinsic or intrinsic factors determined lifespan. Using these methods, platelet lifespans were found to be significantly shortened in thrombopoietin-receptor-deficient mice independent of blood loss, and the antiapoptotic protein Bcl-X(L) was shown to play a role in prolonging erythrocyte lifespans. CONCLUSIONS: The simultaneous study of platelet and erythrocyte lifespans using in vivo CFSE labeling with lognormal modeling yielded insight into common intrinsic and extrinsic platelet and erythrocyte lifespan determinants and provides an improved methodology for use in this field of research. PMID- 20298743 TI - The systems approach to the prespore-specific activation of sigma factor SigF in Bacillus subtilis. AB - The prespore-specific activation of sigma factor SigF (sigma(F)) in Bacillus subtilis has been explained mainly by two factors, i.e., the transient genetic asymmetry and the volume difference between the mother cell and the prespore. Here, we systematically surveyed the effect of these two factors on sporulation using a quantitative modeling and simulation architecture named hybrid functional Petri net with extension (HFPNe). Considering the fact that the transient genetic asymmetry and the volume difference in sporulation of B. subtilis finally bring about the concentration difference in two proteins SpoIIAB (AB) and SpoIIAA (AA) between the mother cell and the prespore, we have surveyed the effect of AB and AA concentration on the prespore-specific activation of sigma(F) occurring in the early stage of sporulation. Our results show that the prespore-specific activation of sigma(F) could be governed by the ratio of AA to AB rather than their concentrations themselves. Our model also suggests that B. subtilis could maximize the ratio of AA to AB in the prespore and minimize it in the mother cell by employing both the transient genetic asymmetry and the volume difference simultaneously. This might give a good explanation to the co-occurrence of the transient asymmetry and the volume difference during sporulation of B. subtilis. In addition, we suggest for the first time that the sigma(F) activation in the prespore might be switched off by the decrease in the ratio of AA to AB after the transient genetic asymmetry is to an end by completion of DNA translocation into the prespore. PMID- 20298744 TI - Seasonal breeding as a neuroendocrine model for puberty in sheep. AB - Puberty is defined as the awakening of the hypothalamic-pituitary gonadal axis. Sheep are seasonal breeders, experiencing an annual period of reproductive quiescence and renaissance that can be utilized as a model for the onset of puberty. Kisspeptin and gonadotropin-inhibitory hormone appear to be important for the seasonal shift in reproductive activity and the former is mandatory for puberty. The non-breeding season is characterized by an increase in the negative feedback effect of estrogen on GnRH and gonadotropin secretion, as is the case in the pre-pubertal period. This effect of estrogen may be transmitted by kisspeptin cells. Additionally, dopaminergic A14/A15 neurons facilitate the seasonal change in estrogen negative feedback. Integrated function of these three groups of neurons appears to modulate the annual shift in photoperiod to a physiological change in fertility. This review compares and contrasts seasonal cycles of reproduction with the mechanisms that relate to the onset of puberty. PMID- 20298745 TI - Genetics and phenomics of Pendred syndrome. AB - Pendred syndrome is an autosomal recessive disorder characterized by sensorineural deafness, goiter and a partial defect in iodide organification. Goiter development and hypothyroidism vary and appear to depend on nutritional iodide intake. Pendred syndrome is caused by biallelic mutations in the SLC26A4 gene, which encodes pendrin, a multifunctional anion exchanger. Pendrin is mainly expressed in the thyroid, the inner ear, and the kidney. In the thyroid, pendrin localizes to the apical membrane of thyrocytes, where it may be involved in mediating iodide efflux. Loss-of-function mutations in the SLC26A4 gene are associated with a partial iodide organification defect, presumably because of a reduced iodide efflux into the follicular lumen. In the kidney, pendrin functions as a chloride/bicarbonate exchanger. In the inner ear, pendrin is important in the maintenance of a normal anion transport and the endocochlear potential. Elucidation of the function of pendrin has provided unexpected novel insights into the pathophysiology of thyroid hormone biosynthesis, chloride retention in the kidney, and composition of the endolymph. PMID- 20298746 TI - Trends in puberty timing in humans and environmental modifiers. AB - Secular trends in timing of puberty appear to continue although under-nutrition has not been any longer a limiting factor for pubertal development. Now obesity and other environmental reasons have been suspected to cause this trend, and endocrine disrupting chemicals have become into focus as possible contributors. Epidemiological studies on endocrine disrupters are still scarce and show only weak associations between exposures and timing of puberty. Since genetic background explains 50-80% of variability in the timing of puberty, it is not surprising that the observed environmental effects are rather modest when individual exposures are assessed. Despite that, some exposures have been reported to be associated to early (e.g., polybrominated biphenyls) or delayed (e.g., lead) puberty. Here we shortly review the available data on recent trends in timing of puberty and the possible role of endocrine disrupters. PMID- 20298747 TI - Genetics and phenomics of hypothyroidism and goiter due to iodotyrosine deiodinase (DEHAL1) gene mutations. AB - Iodotyrosine deiodinase is a thyroidal enzyme that deiodinates mono- and di iodotyrosines (MIT, DIT) and recycles iodine, a scarce element in the environment, for the efficient synthesis of thyroid hormone. Failure of this enzyme leads to hypothyroidism, goiter and mental retardation, a clinical phenotype yet described in the 1950s, whose diagnostic hallmark is the elevation of iodotyrosines in serum and urine. DEHAL1, the gene responsible for this activity, was recently isolated and the molecular basis for the iodotyrosine deiodinase deficiency (ITDD) unraveled. The current clinical picture of mutations in DEHAL1 mostly recapitulates the "classical" phenotype of ITDD, including the psychomotor deficits. This is probably due to the lack of expression of the disease at the beginning of life, which causes ITDD being undetected in current screening programs for congenital hypothyroidism. This worrying feature calls for efforts to improve the preclinical detection of iodotyrosine deiodinase deficiency in the neonatal time. PMID- 20298748 TI - Cleaved bovine prolactin-related protein-I stimulates vascular endothelial cell proliferation. AB - Prolactin-related protein-I (PRP1) is a member of a non-classical prolactin (PRL)/growth hormone family in cattle. However, its function is still unknown. PRL, when cleaved by cathepsin D and matrix metalloproteinases (MMPs), resulted in cleaved N-terminal 16kDa fragments (16K-PRL) that have antiangiogenetic properties in human and rodents. We examined the possibility of similar activity of bovine PRP1. PRP1 (normally 33kDa) was cleaved by cathepsins (CTSs), MMPs, and bovine cotyledonary-conditioned medium (BCCM), and generated mainly 26kDa N terminal fragments. Two specific enzyme families, CTSs and MMPs cleaved intact PRP1, and BCCM also contained PRP1 cleavage activity. Bioactivity for pro- or anti-angiogenesis of the cleaved PRP1 was examined in a cell proliferation assay using bovine brain vascular endothelial cells. The cleaved PRP1 proliferated the endothelial cells in vitro. The endothelial cell proliferation activity of cleaved PRP1 may be shared in specific bovine placentomal angiogenesis. PMID- 20298749 TI - Intra-amygdala injections of neuropeptide S block fear-potentiated startle. AB - Injections of neuropeptide S (NPS) into the lateral ventricle induce a strong hyperactivity. Since most behavioral paradigms are dependent of spontaneous locomotor activity, this makes it difficult to interpret the role of NPS in such paradigms. The aim of the present experiment was to investigate the effects of NPS in fear-potentiated startle, a behavioral fear paradigm which we believe is less sensitive to general changes in locomotor activity. Furthermore, NPS was directly injected into the amygdala, the central site of the neural fear circuitry. Our data shows that intra-amygdala NPS injections dose-dependently block the expression of conditioned fear and that this effect is independent of NPS effects on locomotor activity. This strongly supports a crucial role of amygdaloid NPS in conditioned fear. PMID- 20298750 TI - Activation of imidazoline I2B receptors is linked with AMP kinase pathway to increase glucose uptake in cultured C2C12 cells. AB - Guanidine, the active ingredient extracted from Galega officinalis, is introduced as a ligand for imidazoline I2 receptor (I2R) because guanidine decreased plasma glucose via an activation of I2BR to increase glucose uptake into skeletal muscle isolated from Wistar rats. However, the signals for this action of guanidine remained obscure. In the present study, we used the cultured skeletal muscle fibroblast named C2C12 cell line to investigate this point. We found that guanidine increased the phosphorylation of AMP-activated protein kinase (AMPK) in addition to the higher of glucose transporter GLUT4 expression and glucose uptake. These effects of guanidine were blocked by the pretreatment with I2R antagonist BU224 but not by the blockade of I2AR amiloride. Moreover, compound C at concentrations sufficient to inhibit AMPK blocked the guanidine-induced glucose uptake and GLUT4 protein level. These results suggested that guanidine increases glucose uptake via an activation of I2BR through AMPK activation in skeletal muscle cell; this view has not been mentioned before. PMID- 20298751 TI - Estrogen receptor alpha is involved in the estrogenic regulation of arginine vasopressin immunoreactivity in the supraoptic and paraventricular nuclei of ovariectomized rats. AB - The ovarian hormone estradiol regulates the expression of arginine vasopressin gene and the release of arginine vasopressin by magnocellular hypothalamic neurons. Magnocellular neurons express estrogen receptor beta and are contacted by afferent neurons that express estrogen receptor alpha. In this study we have assessed the effect of selective ligands for estrogen receptors to determine the subtype of estrogen receptor involved in the regulation of arginine vasopressin immunoreactivity in the supraoptic and paraventricular nuclei of ovariectomized rats. The volume fraction occupied by arginine vasopressin immunoreactive material was significantly increased in both nuclei in the animals treated with estradiol compared to the animals injected with vehicle. A similar result was obtained with an estrogen receptor alpha selective agonist. In contrast, the administration of an estrogen receptor beta selective agonist did not significantly affect arginine vasopressin immunoreactivity. This finding suggests that estradiol may regulate arginine vasopressin levels on the supraoptic and paraventricular nuclei by acting on afferent neurons expressing estrogen receptor alpha. PMID- 20298752 TI - Phase-dependent modulation of soleus H-reflex amplitude induced by rhythmic arm cycling. AB - Rhythmic arm cycling is known to suppress the Hoffmann (H-) reflex amplitudes in the soleus (Sol) muscles of stationary legs. However, it has remained unclear if this suppression is modulated according to the phase of movement in the cycle path or is rather a general setting of excitability level related to rhythmic movement. In the present study we investigated the phase-dependent modulation of the Sol H-reflex induced by rhythmic arm cycling by examining reflex amplitudes at 12 phases of the arm cycle movement. Arm cycling tasks consisted of bilateral, ipsilateral and contralateral movement. Additionally, data were also sampled at 12 static arm positions mimicking those occurring during movement. H-reflexes were evoked and recorded at constant motor wave amplitudes across all conditions. Suppression of Sol H-reflex amplitude was dependent upon the phase of movement (main effect p<0.0001) during arm cycling, but not during static positioning. Results suggest that locomotor central pattern generators may contribute to the phasic reflex modulation observed in this study. The phasic modulation was more pronounced during bilateral movement, however aspects of the neural control driving this modulation were also present during ipsilateral and contralateral movement. PMID- 20298753 TI - Oleamide suppresses lipopolysaccharide-induced expression of iNOS and COX-2 through inhibition of NF-kappaB activation in BV2 murine microglial cells. AB - Oleamide (cis-9-octadecenamide) is an endogenous sleep-inducing fatty acid amide that accumulates in the cerebrospinal fluid of the sleep-deprived animals. Microglia are the major immune cells involved in neuroinflammation causing brain damage during infection, ischemia, and neurodegenerative disease. In this study, we examined the effects of oleamide on LPS-induced production of proinflammatory mediators and the mechanisms involved in BV2 microglia. Oleamide inhibited LPS induced production of NO and prostaglandin E2 as well as expression of iNOS and COX-2. We showed that oleamide blocked LPS-induced NF-kappaB activation and phosphorylation of inhibitor kappaB kinase (IKK). We also showed that oleamide inhibited LPS-induced phosphorylation of Akt, p38 MAPK, and ERK, activation of PI 3-kinase, and accumulation of reactive oxygen species (ROS). Finally, we showed that a specific antagonist of the CB2 receptor, AM630, blocked the inhibitory effects of oleamide on LPS-induced production of proinflammatory mediators and activation of NF-kappaB. Taken together, our results suggest that oleamide shows an anti-inflammatory effect through inhibition of NF-kappaB activation in LPS stimulated BV2 microglia. PMID- 20298754 TI - Increased corticospinal excitability induced by unpleasant visual stimuli. AB - Pleasant and unpleasant emotional stimuli are frequently conceptualized as motivators for action. This notion was examined using focal transcranial magnetic stimulation (TMS). Ten healthy participants viewed pleasant, neutral, and unpleasant pictures from the International Affective Picture System (IAPS). During picture viewing, focal TMS was applied to the right motor cortex over the area innervating the first dorsal interosseous muscle of the left hand. Corticomotor excitability was larger while viewing negative pictures than while viewing neutral or positive images, as evidenced by greater motor evoked potentials. No difference was found between pleasant and neutral pictures. These results are consistent with models of emotion in which the neural networks underlying negative emotions have selective, direct connections to brain structures that mediate motor responses. PMID- 20298755 TI - Heterotopically transplanted CVO neural stem cells generate neurons and migrate with SVZ cells in the adult mouse brain. AB - Production of new neurons throughout adulthood has been well characterized in two brain regions, the subventricular zone (SVZ) of the anterolateral ventricle and the subgranular zone (SGZ) of the hippocampus. The neurons produced from these regions arise from neural stem cells (NSCs) found in highly regulated stem cell niches. We recently showed that midline structures called circumventricular organs (CVOs) also contain NSCs capable of neurogenesis and/or astrogliogenesis in vitro and in situ (Bennett et al.). The present study demonstrates that NSCs derived from two astrogliogenic CVOs, the median eminence and organum vasculosum of the lamina terminalis of the nestin-GFP mouse, possess the potential to integrate into the SVZ and differentiate into cells with a neuronal phenotype. These NSCs, following expansion and BrdU-labeling in culture and heterotopic transplantation into a region proximal to the SVZ in adult mice, migrate caudally to the SVZ and express early neuronal markers (TUC-4, PSA-NCAM) as they migrate along the rostral migratory stream. CVO-derived BrdU(+) cells ultimately reach the olfactory bulb where they express early (PSA-NCAM) and mature (NeuN) neuronal markers. Collectively, these data suggest that although NSCs derived from the ME and OVLT CVOs are astrogliogenic in situ, they produce cells phenotypic of neurons in vivo when placed in a neurogenic environment. These findings may have implications for neural repair in the adult brain. PMID- 20298756 TI - Farnesyl diphosphate synthase attenuates paclitaxel-induced apoptotic cell death in human glioblastoma U87MG cells. AB - Increased expression of farnesyl diphosphate synthase (FPPS) by stable transfection appeared to attenuate paclitaxel-induced apoptotic cell death in human glioblastoma U87MG cells. The present results suggest that the apoptotic functions of p53 and c-Jun N-terminal kinase (JNK) are affected by FPPS. Farnesyl diphosphate, a catalytic product of FPPS, also attenuated mentioned paclitaxel induced apoptotic cell death. As expected, the FPPS inhibitor, pamidronate, enhanced paclitaxel-induced apoptotic cell death. The present results suggest that FPPS plays an important role in apoptotic cell death of cancer cells by blocking the JNK signaling cascade and activating mevalonate metabolism in paclitaxel-treated glioblastoma cells. PMID- 20298757 TI - Matrix metalloproteinase-9 (MMP-9) expression and extracellular signal-regulated kinase 1 and 2 (ERK1/2) activation in exercise-reduced neuronal apoptosis after stroke. AB - Exercise preconditioning has been shown to reduce neuronal damage in ischemic/reperfusion (I/R) injury. ERK1/2 signaling in injury has been thought to modulate neuroprotection. In this study, we investigated the effects of ERK1/2 activation on the expression and activity of MMP-9 and downstream neuronal apoptosis. Adult male Sprague-Dawley rats were subjected to 30min of exercise on a treadmill for 3 weeks. Stroke was induced by a 2-h middle cerebral artery (MCA) occlusion using an intraluminal filament. Apoptotic protein caspase-3 and neuronal apoptosis in cortex and striatum was determined by Western blot at 24h reperfusion and TUNEL staining at 48h reperfusion in 5 I/R injury groups: no treatment, MMP-9 inhibitor (doxycycline), pre-ischemic exercise, exercised animals undergone ERK1/2 inhibition (U0126), and dual inhibition of ERK1/2 and MMP-9 in exercised ischemic rats. Cerebral MMP-9 expression in ischemic rats with different treatment was determined at 6, 12 and 24h reperfusion by real-time PCR for mRNA, Western blot for protein and zymography for enzyme activity. Exercise preconditioning significantly (p<0.05) reduced apoptosis determined by caspase-3 and TUNEL. In non-exercised rats, doxycycline treatment had significant (p<0.05) reductions in apoptosis after I/R injury. The dual ERK1/2-MMP-9 inhibited exercised animals had significantly (p<0.05) reduced neuronal apoptosis that was similar to that seen in exercised ischemic rats. MMP-9 expression in I/R injury was significantly (p<0.05) reduced in the exercised animals as compared to non exercised controls. When ERK1/2 was inhibited, the reduced MMP-9 expression was reversed to the level seen in the non-exercised controls. This study has suggested that exercise-induced neuroprotection in I/R injury may be mediated by MMP-9 and ERK1/2 expression, leading to a reduction in neuronal apoptosis. PMID- 20298759 TI - Dose-related effects of memantine on a mismatch negativity-like response in anesthetized rats. AB - Memantine is a low-affinity NMDA receptor antagonist that is used in the treatment of Alzheimer's disease to alleviate the cognitive symptoms of the disease. In humans, memantine has been shown to facilitate auditory change detection as reflected in the mismatch negativity (MMN) response recorded in the frontal cortex. In the present study we investigated the effects of memantine on the auditory MMN-like responses recorded in anesthetized rats. Saline, a low (3 mg/kg) or a high (10 mg/kg) dose of memantine was i.p. injected into the animals. Auditory MMN-like responses were recorded during the presentation of a repeated tone of one frequency (standard, P=0.956) that was rarely replaced by a tone of another frequency (deviant, P=0.044). The low dose of memantine did not observably affect the amplitude of the auditory MMN-like response, but it prolonged the duration of the response relative to saline. The high dose of memantine, in contrast, blocked the generation of the auditory MMN-like response. The findings suggest that memantine may, with appropriate doses, facilitate already this early stage of auditory processing. PMID- 20298758 TI - Is age-dependent, ketamine-induced apoptosis in the rat somatosensory cortex influenced by temperature? AB - General anesthetics have long been thought to be relatively safe but recent clinical studies have revealed that exposure of very young children (4 years or less) to agents that act by blocking the N-methyl-D-aspartate receptor (NMDAR) can lead to cognitive deficits as they mature. In rodent and non-human primate studies, blockade of this receptor during the perinatal period leads to a number of molecular, cellular and behavioral pathologies. Despite the overwhelming evidence from such studies, doubt remains as to their clinical relevance. A key issue is whether the primary injury (apoptotic cell death) is specific to receptor blockade or due to non-specific, patho-physiological changes. Principal to this argument is that loss of core body temperature following NMDAR blockade could explain why injury is observed hours later. We therefore examined the neurotoxicity of the general anesthetic ketamine in P7, P14 and P21 rats while monitoring core body temperature. We found that, at P7, ketamine induced the pro apoptotic enzyme activated caspase-3 in a dose-dependent manner. As expected, injury was greatly diminished by P14 and absent by P21. However, contrary to expectations, we found that core body temperature was not a factor in determining injury. Our data imply that injury is directly related to receptor blockade and is unlikely to be overcome by artificially changing core body temperature. PMID- 20298760 TI - Amphetamine up-regulates activator of G-protein signaling 1 mRNA and protein levels in rat frontal cortex: the role of dopamine and glucocorticoid receptors. AB - Acute and chronic exposure to psychostimulants results in altered function of G protein-coupled receptors in the forebrain. It is believed that neuroadaptations in G-protein signaling contribute to behavioral sensitivity to psychostimulants that persists over a prolonged drug-free period. Proteins termed activators of G protein signaling (AGS) have been characterized as potent modulators of both receptor-dependent and receptor-independent G-protein signaling. Nevertheless, the regulation of AGS gene and protein expression by psychostimulants remains poorly understood. In the present study, we investigated amphetamine (AMPH) induced changes in expression patterns of several forebrain-enriched AGS proteins. A single exposure to AMPH (2.5 mg/kg i.p.) selectively induced gene expression of AGS1, but not Rhes or AGS3 proteins, in the rat prefrontal cortex (PFC) as measured 3 h later. Induction of AGS1 mRNA in the PFC by acute AMPH was transient and dose-dependent. Even repeated treatment with AMPH for 5 days did not produce lasting changes in AGS1 mRNA and protein levels in the PFC as measured 3 weeks post treatment. However, at this time point, a low dose AMPH challenge (1 mg/kg i.p.) induced a robust behavioral response and upregulated AGS1 expression in the PFC selectively in animals with an AMPH history. The effects of AMPH on AGS1 expression in the PFC were blocked by a D2, but not D1, dopamine receptor antagonist and partially by a glucocorticoid receptor antagonist. Collectively, the present study suggests that (1) AGS1 represents a regulator of G-protein signaling that is rapidly inducible by AMPH in the frontal cortex, (2) AGS1 regulation in the PFC parallels behavioral activation by acute AMPH in drug-naive animals and hypersensitivity to AMPH challenge in sensitized animals, and (3) D2 dopamine and glucocorticoid receptors regulate AMPH effects on AGS1 in the PFC. Changes in AGS1 levels in the PFC may result in abnormal receptor-to-G-protein coupling that alters cortical sensitivity to psychostimulants. PMID- 20298762 TI - Hydroxylase inhibition reduces synaptic transmission and protects against a glutamate-induced ischemia in the CA1 region of the rat hippocampus. AB - The discovery of hydroxylases as oxygen sensors and key regulators of hypoxia induced gene expression has made them a novel target for manipulating the transcriptional response to hypoxia for therapeutic benefit. In this study we have investigated the effect of prolyl hydroxylase inhibition on synaptic activity in hippocampal slices and compared this to the changes occurring following exposure to hypoxia. Furthermore, we investigated a potentially protective role for hydroxylase inhibition against a glutamate-induced ischemic insult in the CA1 region of organotypic hippocampal cultures. Application of the hydroxylase inhibitor, dimethyloxallyl glycine (DMOG), depressed synaptic transmission. Both hypoxia and DMOG induced a reversible reduction in synaptic transmission, enhanced paired pulse facilitation (P<0.05) and inhibited N-methyl d-aspartate receptor (NMDAR) activity (P<0.01). However the effects of DMOG were adenosine A(1) receptor independent. Our results also suggest a potential therapeutic application for prolyl 4-hydroxylase (PHD) inhibitors in cerebral ischemia, since DMOG protected the CA1 region in organotypic hippocampal slices against a glutamate-induced ischemic insult. PMID- 20298763 TI - MDMA causes a redistribution of serotonin transporter from the cell surface to the intracellular compartment by a mechanism independent of phospho-p38-mitogen activated protein kinase activation. AB - 3,4-methylenedioxymethamphetamine (MDMA) causes long-term serotonin depletion and reduced serotonin transporter (SERT) function in humans and in animal models. Using quantitative Western blotting and real-time PCR, we have shown that total SERT protein in the striatum and nucleus accumbens and mRNA levels in the dorsal raphe nucleus were not significantly changed following MDMA exposure in rats (4 x 2 h i.p. injections, 10 mg/kg each). In mouse neuroblastoma (N(2)A) cells transiently expressing green fluorescent protein-tagged human SERT (GFP-hSERT), we have shown redistribution of SERT from the cell surface to intracellular vesicles on exposure to MDMA using cell surface biotinylation, total internal reflection fluorescence microscopy (TIRFM) and live-cell confocal microscopy. To investigate the mechanism responsible for SERT redistribution, we used specific antibodies to phospho-p38-mitogen activated protein kinase (p38 MAPK), a known signalling pathway involved in SERT membrane expression. We found that p38 MAPK activation was not involved in the MDMA-induced redistribution of SERT from the cell-surface to the cell interior. A loss of SERT from the cell surface on acute exposure to MDMA may contribute to the decreased SERT function seen in rats exposed to MDMA. PMID- 20298761 TI - Salicylate-induced degeneration of cochlea spiral ganglion neurons-apoptosis signaling. AB - Aspirin, whose active ingredient is sodium salicylate, is the most widely used drug worldwide, but it is not recommended for children because it may cause Reye's syndrome. High doses of salicylate also induce temporary hearing loss and tinnitus; while these disorders are believed to disappear when treatment is discontinued some data suggest that prolonged treatment may be neurotoxic. To investigate its ototoxicity, immature, postnatal day 3 rat cochlear organotypic cultures were treated with salicylate. Salicylate did not damage the sensory hair cells, but instead damaged the spiral ganglion neurons (SGN) and their peripheral fibers in a dose-dependent manner. The cross-sectional area of SGN decreased from 205 microm(2) in controls to 143, 116, and 91 microm(2) in cultures treated with 1, 3, or 5 mM salicylate, respectively. Morphological changes and caspase upregulation were indicative of caspase-mediated apoptosis. A quantitative RT-PCR apoptosis array identified a subset of genes up- or down regulated by salicylate. Eight genes showed a biologically relevant change (P<0.05, > or =2 fold change) after 3 h treatment with salicylate; seven genes (Tp53, Birc3, Tnfrsf5, Casp7, Nfkb1, Fas, Lta, Tnfsf10) were upregulated and one gene (Pycard) was downregulated. After 6 h treatment, only one gene (Nol3) was upregulated and two genes were downregulated (Cideb and Lhx4) while after 12 h treatment, two genes (Il10, Gadd45a) were upregulated and 4 (Prok2, Card10, Ltbr, Dapk1) were downregulated. High doses of salicylate in a physiologically relevant range can induce caspase-mediated cell death in immature SGN; changes in the expression of apoptotic genes particularly among members of the tumor necrosis factor (TNF) family appear to play an important role in the degeneration. PMID- 20298765 TI - The hidden variables of leadership. AB - The dynamics of a collective move can be untangled into three components: initiation, following and cancellation. Varying the response function parameters attached to one individual can switch the collective phenomenology from an absence of well identified leader ("distributed leadership") to the emergence of a "despotic regime", i.e. this individual leading more often the collective moves. I show that not all parameters have the same impact but rather that only a large increase of the initiation rate can empower an obvious leader, up to the "despotic" regime. Being more readily followed, or cancelling less often can enhance the leader's prominence only up to a limited level. To overtake this limit would then further require to affect also the parameters attached to the others (e.g. to lower their eagerness to initiate group motion as well as their probability to be followed when they do). PMID- 20298764 TI - Neural heterogeneities and stimulus properties affect burst coding in vivo. AB - Many neurons tend to fire clusters of action potentials called bursts followed by quiescence in response to sensory input. While the mechanisms that underlie burst firing are generally well understood in vitro, the functional role of these bursts in generating behavioral responses to sensory input in vivo are less clear. Pyramidal cells within the electrosensory lateral line lobe (ELL) of weakly electric fish offer an attractive model system for studying the coding properties of burst firing, because the anatomy and physiology of the electrosensory circuitry are well understood, and the burst mechanism of ELL pyramidal cells has been thoroughly characterized in vitro. We investigated the coding properties of bursts generated by these cells in vivo in response to mimics of behaviorally relevant sensory input. We found that heterogeneities within the pyramidal cell population had quantitative but not qualitative effects on burst coding for the low frequency components of broadband time varying input. Moreover, spatially localized stimuli mimicking, for example, prey tended to elicit more bursts than spatially global stimuli mimicking conspecific-related stimuli. We also found small but significant correlations between burst attributes such as the number of spikes per burst or the interspike interval during the burst and stimulus attributes such as stimulus amplitude or slope. These correlations were much weaker in magnitude than those observed in vitro. More surprisingly, our results show that correlations between burst and stimulus attributes actually decreased in magnitude when we used low frequency stimuli that are expected to promote burst firing. We propose that this discrepancy is attributable to differences between ELL pyramidal cell burst firing under in vivo and in vitro conditions. PMID- 20298768 TI - Potential use of gamma-cyclodextrin polypseudorotaxane hydrogels as an injectable sustained release system for insulin. AB - The development of injectable hydrogels for protein delivery is a major challenge. In this study, insulin/alpha-cyclodextrin (alpha-CyD) and gamma-CyD polypseudorotaxane (PPRX) hydrogels were prepared through inclusion complexation between high molecular weight poly(ethylene glycol) (PEG) and CyDs. The alpha-CyD and gamma-CyD PPRX hydrogels were formed by inserting one PEG chain in the alpha CyD cavity and two PEG chains in the gamma-CyD cavity. Insulin/CyD PPRX hydrogel formation was based on physical crosslinking induced by self-assembling without chemical crosslinking reagent. The supramolecular structures of insulin/CyD PPRX hydrogels were confirmed with (1)H nuclear magnetic resonance ((1)H NMR), X-ray diffraction, differential scanning calorimetry (DSC) and scanning electron microscopy (SEM). The in vitro release study showed that the release rate of insulin from the CyDs PPRX hydrogels decreased in the order of gamma-CyD PPRX hydrogel>alpha-CyD PPRX hydrogel. This decrease was controlled by the addition of CyDs to the medium. The serum insulin level after subcutaneous administration of gamma-CyD PPRX hydrogel to rats was significantly prolonged, accompanying with an increase in the area under serum concentration-time curve, which was clearly reflected in the prolonged hypoglycemic effect. In conclusion, these results suggest the potential use of gamma-CyD PPRX hydrogel as an injectable sustained release system for insulin. PMID- 20298767 TI - Preparation and properties of branched oligoglycerol modifiers for stabilization of liposomes. AB - We examined the effect on drug delivery of liposomes with surfaces that were modified with branched oligoglycerols (BGLs) and explored possible formulation advantages to increase drug exposure. BGL012 is a branched oligoglycerol derivative with a cascade-like structure of 12 glycerol units, characterized as a widely spread structure in aqueous solution. We prepared BGL-phospholipid derivatives (BGL-PEs), including BGL012, by coupling 1,2 distearoylphosphatidylethanolamine to BGLs. BGL012-PE modification of the liposomes (BGL012L) achieved a long circulation time after intravenous injection in rats. The circulation lifetime of BGL012L was almost the same as that of polyethylene glycol (PEG)-modified liposomes. The surface of BGL012L induced the formation of a fixed aqueous layer and reduced protein adsorption on the liposome surface, without strong interference with the binding reaction on the liposome. Thus, the newly synthesized branched oligoglycerol derivatives are considered to have useful hydrophilic and physical properties for modifying the liposome surface to increase drug exposure. PMID- 20298769 TI - Folate-PEG modified poly(2-(2-aminoethoxy)ethoxy)phosphazene/DNA nanoparticles for gene delivery: synthesis, preparation and in vitro transfection efficiency. AB - Target-specific technique can significantly enhance the efficacy of gene delivery system which was limited by many cellular barriers. In this work, a new folate PEG modified poly(2-(2-aminoethoxy)ethoxy)phosphazene (PAEP), namely, folate-PEG PAEP was synthesized as a folate receptor (FR) targeted carrier, and the cytotoxicity, transfection efficiency, cellular uptake and intracellular trafficking of folate-PEG-PAEP/DNA nanoparticles (FPPN) were investigated. Compared with the PAEP/DNA nanoparticles (PN), the cytotoxicity of FPPN decreased significantly at high dose. FPPN showed much higher transfection efficiency (15.85+/-1.23%) compared with PN (6.71+/-0.42%) in FR overexpressing Hela cells, but no significant difference was observed in CHO-k1 cells lacking FR. The transfection activity of FPPN could be reversed in the presence of 1.0mM free folic acid in Hela cells. The cellular uptake of FPPN was 37.38% higher than that of PN in Hela cells. These results indicated that FPPN could be a potential targeted gene delivery system. PMID- 20298770 TI - In vivo efficacy of paclitaxel-loaded injectable in situ-forming gel against subcutaneous tumor growth. AB - Injectable in situ-forming gels have received considerable attention as localized drug delivery systems. Here, we examined a poly(ethylene glycol)-b polycaprolactone (MPEG-PCL) diblock copolymer gel as an injectable drug depot for paclitaxel (Ptx). The copolymer solution remained liquid at room temperature and rapidly gelled in vivo at body temperature. In vitro experiments showed that Ptx was released from MPEG-PCL copolymer gels over the course of more than 14 days. Experiments employing intratumoral injection of saline (control), gel-only, Taxol, or Ptx-loaded gel into mice bearing B16F10 tumor xenografts showed that Ptx-loaded gel inhibited the growth of B16F10 tumors more effectively than did saline or gel alone. Further, intratumoral injection of Ptx-loaded gel was more efficacious in inhibiting the growth of B16F10 tumor over 10 days than was injection of Taxol. A histological analysis demonstrated an increase in necrotic tissue in tumors treated with Ptx-loaded gel. In conclusion, our data show that intratumoral injection of Ptx-loaded MPEG-PCL diblock copolymer yielded an in situ-forming gel that exhibited controlled Ptx release profile, and that was effective in treating localized solid tumors. PMID- 20298771 TI - A charge-switched nano-sized polymeric carrier for protein delivery. AB - A novel synthetic nanocomplex was constructed from glycol chitosan (GCS) grafted with 2,3-dimethylmaleic anhydride (DMA) (denoted as 'GCD' hereafter) and lysozyme (isoelectric point=10.9) as a model protein. This is a core-shell supramolecular assemble formed through electrostatic interactions between anionic GCD and cationic lysozyme at a pH 7.4. The pH-sensitivity of the nanocomplexes originates from the dissociation of DMA block from GCD at a slightly acidic pH (i.e., pH 6.8), resulting in an increased electrostatic repulsion between cationic GCS and cationic lysozyme. This pH-induced charge switching of GCD provides a mechanism for triggered protein drug release from the nanocomplexes triggered by the small change in pH (pH 7.4-6.8). PMID- 20298772 TI - Antimicrobial and antimalarial activity of Cussonia species (Araliaceae). AB - ETHNOPHARMACOLOGICAL RELEVANCE: Cussonia species are used in African traditional medicine mainly against pain, inflammation, gastro-intestinal problems, malaria and sexually transmitted diseases. AIM OF THE STUDY: To summarise ethnomedicinal uses of Cussonia and to find scientific evidence in support of selected main uses. MATERIALS AND METHODS: Using the minimum inhibitory concentration (MIC) method, leaves of 13 Cussonia species, Schefflera umbellifera and Seemannaralia gerrardii were tested against pathogens associated with diarrhoea (Enterococcus faecalis and Escherichia coli), sexually transmitted infections (Neisseria gonorrhoeae and Trichomonas vaginalis) and general infectious diseases (Staphylococcus aureus and Pseudomonas aeruginosa). Antimalarial sensitivity was studied using Plasmodium falciparum and the [(3)H]-hypoxanthine incorporation assay. Cytotoxic effects on a T-cell leukaemia (Jurkat) cell line were determined using the tetrazolium-based cellular toxicity assay. RESULTS: Methanolic extracts were active against Pseudomonas aeruginosa (MIC of 1.0-1.5 mg/mL), Trichomonas vaginalis (MIC of 0.8-1.3 mg/mL) and Staphylococcus aureus (Cussonia arborea, 1.8 mg/mL). All samples were active against Neisseria gonorrhoeae (MIC of 0.02-0.7 mg/mL). The methanol extract of Cussonia arborea was the most active against Plasmodium falciparum (13.68 microg/mL) and showed anticancer properties (5.60 microg/mL). CONCLUSIONS: The traditional use of Cussonia species to treat sexually transmitted diseases and Plasmodium infections appears to have a scientific basis. PMID- 20298773 TI - Cell surface hydrophobicity, biofilm formation, adhesives properties and molecular detection of adhesins genes in Staphylococcus aureus associated to dental caries. AB - Staphylococcus aureus is an important pathogen that forms biofilm. In this study, 22 S. aureus have been isolated from the oral cavity of Tunisian children and investigated for slime production using Congo red agar method (CRA) and semi quantitative adherence assay. The hydrophobicity of strains was evaluated by the microbial adhesion to solvent (MATS) test. The adherence of S. aureus to Hep2 cells was examined by light microscopy. The genes implicated in adhesion (icaA, icaD, fnbA, cna, clfA) were detected. Polymerase chain reaction was used. The affinity to hexadecane was low proving a hydrophilic character of all the studied strains. Qualitative biofilm production revealed that 50% of strains were slime producers. The result of OD(570) showed that four strains isolated from the caries-active children were highly biofilm positive. In addition, 50% of strains were icaA and icaD positive. The fnbA gene was present in 59.1% of isolated strains. Furthermore, 54.5% of strains harboured the cna gene, 9.1% were clfA positive and 50% were hla positive. Quantitative adherence varied considerably among the tested strains. All strains showed adherence to Hep2 cells. However, the level of adhesion varied between strains as follows. Seven strains were defined as moderately adherent, nine as strongly adherent and six as weakly adherent. The percentage of infected cells ranged from 15+/-0.0376 (B374) to 96+/ 0.019 (B295) and the total number of bacteria per 100 cells ranged from 15+/-5.1 (B374) to 1824+/-30.1 (B295). PMID- 20298774 TI - Amino acid regions 357-368 and 418-427 of Streptococcus pyogenes 60kDa heat shock protein are recognized by antibodies from glaucomatous patient sera. AB - Heat shock protein 60kDa (HSP60) could be involved in glaucoma because its expression in optical nerve, and autoantibodies to HSP60 have been found in glaucomatous patients; however, HSP60 antigenic sites recognized by glaucomatous patients are unknown. Therefore, in this work, the antibody levels in the sera of glaucoma patients, and HSP60 antigenic sites were determined. Analysis by the Hopp and Woods method with GENE 2.2 software identified the possible antigenic sites in the amino acid regions 200-213, 226-237, 278-290, 357-368 and 418-427 of Streptococcus pyogenes HSP60 (HSP60Sp). According to these, polypeptides were generated truncating the hsp60Sp gene by PCR. Antibody levels to HSP60Sp and the generated polypeptides were measured by ELISA in serum of glaucomatous patients and in healthy subjects. Glaucomatous patients showed higher antibody levels to rHSP60Sp (p=0.002) than healthy subjects. We found that the high anti-rHSP60Sp antibody levels are associated with the disease (OR=5.2; IC95% of 1.6-16.7; p<0.05). Here we report that amino acid regions 357-368 and 418-427 of HSP60Sp are the main antigenic sites, because when they are absent the level of anti HSP60 antibodies decreased around 80%. These results suggest that the regions 357 368 and 418-427 of HSP60Sp could be associated with glaucoma. PMID- 20298775 TI - BAC library for the amphipod crustacean, Parhyale hawaiensis. AB - Bacterial artificial chromosomes (BACs) are capable of propagating large fragments of DNA and have become an invaluable tool for studying genome biology. To fill a phylogenetic gap in available genomic sequence and to complement ongoing molecular and genetic studies, we have generated a BAC library for the marine amphipod crustacean, Parhyale hawaiensis. The library was generated from genomic DNA isolated from whole adult animals and comprises 129,024 individual clones. The median insert size is approximately 140 kb and the genomic coverage is approximately five genome equivalents. We have screened the Parhyale BAC library for developmentally relevant genes and characterized the genomic organization of four genes: a hedgehog ortholog, and three Pax3/7 paralogs. Preliminary analysis suggests that introns are larger and more prevalent in Parhyale than in other arthropods whose genomes have been sequenced, which may partly account for the large genome size in Parhyale. PMID- 20298777 TI - Human transcriptome nexuses: basic-eukaryotic and metazoan. AB - Using a new approach, I analysed human transcriptome coexpression network and revealed two large-scale nexuses. Besides gene coexpression, each nexus is characterized by a combination of gene evolutionary origin, function and among tissues expression breadth. The first nexus contains mostly genes of pre-metazoan origin, which are widely expressed and have cell-centred functions. The second nexus is enriched in genes of metazoan origin, which are expressed more narrowly and have organism-centred functions. The revealed nexuses are supported by asymmetry in distribution of transcription factor targets between them. Within the metazoan nexus, there is a subnexus that is more pronounced in the nervous tissues and is enriched in gene regulatory complexity. It mostly contains genes related to nervous system, cell communication and multicellular organism processes and development. The revealed nexuses indicate a dichotomy in the transcriptional regulation and can provide a framework for further functional genomics studies. PMID- 20298776 TI - Exploring mitochondrial evolution and metabolism organization principles by comparative analysis of metabolic networks. AB - The endosymbiotic theory proposed that mitochondrial genomes are derived from an alpha-proteobacterium-like endosymbiont, which was concluded from sequence analysis. We rebuilt the metabolic networks of mitochondria and 22 relative species, and studied the evolution of mitochondrial metabolism at the level of enzyme content and network topology. Our phylogenetic results based on network alignment and motif identification supported the endosymbiotic theory from the point of view of systems biology for the first time. It was found that the mitochondrial metabolic network were much more compact than the relative species, probably related to the higher efficiency of oxidative phosphorylation of the specialized organelle, and the network is highly clustered around the TCA cycle. Moreover, the mitochondrial metabolic network exhibited high functional specificity to the modules. This work provided insight to the understanding of mitochondria evolution, and the organization principle of mitochondrial metabolic network at the network level. PMID- 20298778 TI - Efficacy of a new sustained-release microsphere formulation of exenatide, DA 3091, in Zucker diabetic fatty (ZDF) rats. AB - Exenatide must be administered serially by twice-daily subcutaneous (SC) injection due to its short half-life. The purpose of the present study is to develop an improved sustained-release exenatide formulation with a therapeutic efficacy comparable to serial, twice-daily injections of exenatide. A novel SR formulation of exenatide, DA-3091, was prepared by single-emulsion solvent evaporation using PLGA. It was administered by SC injection to ZDF rats in single exenatide doses of 0.1, 0.25, 0.5, 1 or 2mg/kg. On the 28th, 49th and 70th days, a 1 or 2mg/kg dose of DA-3091 was further administered to rats in dose groups of 1 or 2mg/kg. The efficacy of DA-3091 was then compared with that of serial, twice daily SC injections of an exenatide solution for 13 weeks. NFBG and HbA1c concentrations were decreased both significantly and linearly as the exenatide dose in DA-3091 increased. In addition, food intake and body weight were suppressed both significantly and dose-dependently. In equivalent or half doses of exenatide, the efficacy of DA-3091 was comparable to that of twice-daily injections of exenatide solution for 13 weeks. In conclusion, DA-3091 has the potential to be clinically effective when administered every 3 weeks, or less frequently, which promises to significantly improve patient compliance. PMID- 20298779 TI - Lactoferrin-modified procationic liposomes as a novel drug carrier for brain delivery. AB - In this study, a new drug carrier for brain delivery, lactoferrin-modified procationic liposome, was developed and evaluated in vitro and in vivo. The procationic liposomes (PCLs) were neutral or negatively charged at physiological pH, and when they touched brain capillary endothelial cells with the help of a brain-targeting ligand, lactoferrin (Lf), they were changed into cationic liposomes (CL). The PCLs and lactoferrin-modified procationic liposomes (Lf-PCLs) with different CHETA/Lf ratio were prepared and characterized. The primary brain capillary endothelial cells (BCECs) were cultured to investigate the potential cytotoxicity and uptake of liposomes in vitro. An in vitro model of the blood brain barrier (BBB), developed by the co-culture of BCECs and astrocytes (ACs), was employed to evaluate the ability and mechanisms of liposomes to cross endothelial cells. The liposome uptake by the mouse brain in vivo was detected by HPLC-fluorescence analysis. The results indicated that compared with the conventional liposomes and CLs, PCL and Lf-PCLs showed an improved performance in the uptake efficiency and cytotoxicity. Besides the uptake mediated by clathrin dependent endocytosis of PCL, Lf-PCL crossed the BCECs through lipid raft/caveloae-mediated endocytosis. The endocytosis involved in the transport of Lf-PCL crossing BBB was mediated by both receptor- and absorption-mediated transcytosis. Compared with the conventional liposomes, PCL and Lf-PCL-8 (CHETA/Lf ratio=1:8, w/w) were observed to show much improved characteristics of the localization in the brain. This study suggested that Lf-PCL was an available brain drug delivery carrier with potential future application. PMID- 20298780 TI - Lyotropic, liquid crystalline nanostructures of aqueous dilutions of SMEDDS revealed by small-angle X-ray scattering: impact on solubility and drug release. AB - The present study was conducted to characterise the liquid crystalline phases that occur upon diluting a SMEDDS and to elucidate the role of these phases on drug solubilisation and release. Small-angle X-ray scattering (SAXS) was used to probe the structures in aqueous dilutions of 3 SMEDDS consisting of propylene glycol mono- and dicaprylate and mono- and dicaprate (PGDCDC) and d-alpha tocopheryl polyethylene glycol succinate 1000 (TPGS 1000), polysorbate 80 (P80) or polyoxyl 40 hydrogenated castor oil (P40HC). The scattering patterns revealed the formation of either a random periodic or a lamellar phase when 10% (w/w) water was added. All formulations exhibited lamellar structures at 20% (w/w) aqueous dilution, of which the layer-to-layer distance increased upon further addition of water. At 40% (w/w) water, a hexagonal or lamellar phase was formed, depending on the geometry of the surfactant. Temperature did not alter the phases formed. Incorporation of the drug UC 781 only slightly enlarged the characteristic dimensions of the liquid crystalline phases. Drug solubility decreased upon aqueous dilution, although 10% (w/w) dilutions of PGDCDC-P80 SMEDDS and PGDCDC-TPGS 1000 SMEDDS revealed a highly increased solubility as compared to the pure formulations. Drug release data revealed that UC 781 release could not be linked to the solubilisation capacity of the SMEDDS, but could be associated with the solubility of UC 781 in the phases formed at water concentrations above 10% (w/w). PMID- 20298781 TI - The effect of dehydration conditions on the functionality of anhydrous amorphous raffinose. AB - The purpose of this investigation is to study the effect of dehydration conditions of raffinose pentahydrate (RF.5H2O) on the physical properties and functionality of the resulting material. Crystalline RF.5H2O was dehydrated at two temperatures, 80 degrees C and 110 degrees C, producing the amorphous anhydrous form (RF.am). The dehydration temperature had no effect on a number of physical properties of the obtained RF.am, including X-ray powder diffraction, surface energy and water uptake. However, despite resulting on the same dynamics and extent of water sorption, different dehydration temperatures produced amorphous samples with drastically different recrystallization tendencies. Thermodynamic parameters show that despite the similarities on certain physical attributes, different dehydration temperature results in samples with significantly different free energy, hence stability. The difference in free energy produced by the dehydration temperature is attributed to differences in supramolecular structure that persist even in the liquid domain (above T(g)) of the amorphous samples. Evidence of such effects is observed as fluctuations in heat capacity present in RF.am but absent in the freshly prepared glass and also supported by the presence of molecular mobility modes observed using thermal polarization measurements. PMID- 20298782 TI - Sun exposure questionnaire predicts circulating 25-hydroxyvitamin D concentrations in Caucasian hospital workers in southern Italy. AB - INTRODUCTION: Recent sun exposure should correlate with circulating 25 hydroxyvitamin D [25(OH)D] due to ultraviolet B (UVB)-catalyzed cutaneous synthesis of vitamin D. METHODS: A Sun Exposure Score was calculated for healthy adults using a recall questionnaire assessing daily Time in Sun (<5 min, 5-30 min, >30 min) and Skin Exposure (face/hands; face/hands and arms; face/hands and legs; and "bathing suit") for 1 week in each of the winter and summer (n=47 and 23, respectively; n=18 participated in both). Concentrations of 25(OH)D were measured by DiaSorin RIA on end-of-week sera. RESULTS: Mean serum 25(OH)D was higher in summer than winter (58.6+/-16.5 nmol/L vs. 38.8+/-29.0 nmol/L, respectively, P=0.003 unpaired). The calculated Sun Exposure Score correlated strongly with serum 25(OH)D during summer (Spearman's rho=0.59, P=0.003); based on the Pearson coefficient of determination, summer Sun Exposure Score explained 38% of the variability in summer serum 25(OH)D. The Sun Exposure Score did not correlate with 25(OH)D in the winter (rho=0.19, P=0.210). The summer correlation was largely explained by the Time in Sun (rho=0.58, P=0.004) rather than area of Skin Exposed (rho=0.10, P=0.660). Although there was a correlation between winter and summer Sun Exposure Scores (rho=0.63, P=0.005), there was no summer vs. winter correlation in serum 25(OH)D (rho=0.08, P=0.76). CONCLUSION: This simple 1 week sun exposure recall questionnaire predicted summer serum 25(OH)D concentrations, accounting for 38% of the variability in 25(OH)D among healthy Italian adults. PMID- 20298783 TI - Physical activity and estrogen treatment reduce visceral body fat and serum levels of leptin in an additive manner in a diet induced animal model of obesity. AB - Estrogen replacement and physical activity have been demonstrated to reduce the risk to develop a metabolic syndrome in postmenopausal women. In this study we investigate the combined effects of endurance training and estrogen substitution in a rat animal model of diet induced obesity. Effects on lipid and glucose metabolism were evaluated. Ovariectomized (OVX) or sham-operated (SHAM) female Wistar rats were fed with a high fat diet (HF) for 9 weeks. After 3 weeks of overnutrition the OVX rats either remained sedentary, performed treadmill training, received 17beta-Estradiol (E(2)), or combined treatment. The OVX rats had a greater increase in body weight and serum levels of cholesterol, triglyceride and low-density lipoprotein cholesterol (LDL). These parameters could be reduced by E(2) and more effectively E(2) in combination with exercise. Also the increase of visceral body fat and leptin could be improved by E(2) and exercise. This combination showed synergistic effects. Serum levels of insulin could be reduced by exercise training, E(2) substitution revealed no significant changes. Our results indicate that ovariectomy increases the susceptibility to develop obesity. In addition they show that the combination of hormone replacement therapy (HRT) and physical activity may influence parameters related to lipid metabolism positively in an additive manner. The results of this study provide evidence that the combination of HRT with physical activity could be a very effective strategy to prevent the development of a metabolic syndrome induced by overnutrition. PMID- 20298784 TI - Comparison of the effects of eldecalcitol and alfacalcidol on bone and calcium metabolism. AB - Eldecalcitol [ED-71, 2beta-(3-hydroxypropyloxy)-1,25-dihydroxyvitamin D3] increases lumbar and hip bone mineral density (BMD) in a dose-dependent manner in osteoporotic patients with vitamin D supplementation. However, there has been no head-to-head comparison of the effects of eldecalcitol with alfacalcidol on bone and calcium metabolism in human subjects. Therefore, a randomized open-label clinical trial was conducted to compare the effect of eldecalcitol on bone turnover markers and calcium metabolism in 59 Japanese postmenopausal women. Subjects were randomly assigned to receive 1.0 microg alfacalcidol, 0.5 or 1.0 microg eldecalcitol once a day for 12 weeks. There was almost no increase in serum calcium (Ca) throughout the study period. Eldecalcitol from 0.5 to 1.0 microg increased daily urinary Ca excretion in a dose-dependent manner, and 1.0 microg eldecalcitol increased urinary Ca to a similar extent to 1.0 microg alfacalcidol. Both 0.5 and 1.0 microg eldecalcitol suppressed urinary NTX stronger than 1.0 microg alfacalcidol (-6, -30 and -35% in 1.0 microg alfacalcidol, 0.5 and 1.0 microg eldecalcitol-treated groups, respectively, at 12 weeks). In contrast, changes in serum BALP were similar among the three groups ( 22, -22 and -29% in 1.0 microg alfacalcidol, 0.5 and 1.0 microg eldecalcitol treated groups, respectively, at 12 weeks). These results demonstrate that 0.5 1.0 microg eldecalcitol can effectively inhibit bone resorption stronger than alfacalcidol with a similar effect on bone formation and a comparable effect on urinary Ca excretion, and suggest that eldecalcitol may have a better osteoprotective effect than alfacalcidol. PMID- 20298785 TI - Differential regulation of epidermal function by VDR coactivators. AB - The transcriptional activity of the vitamin D receptor (VDR) is regulated by a number of coactivator and corepressor complexes, which bind to the VDR in a ligand (1,25(OH)2D3) dependent (coactivators) or inhibited (corepressors) process. In the keratinocyte the major coactivator complexes include the vitamin D interacting protein (DRIP) complex and the steroid receptor coactivator (SRC) complexes. These coactivator complexes are not interchangeable in their regulation of keratinocyte proliferation and differentiation. We found that the DRIP complex is the main complex binding to VDR in the proliferating keratinocyte, whereas SRC2 and 3 and their associated proteins are the major coactivators binding to VDR in the differentiated keratinocyte. Moreover, we have found a specific role for DRIP205 in the regulation of beta-catenin pathways regulating keratinocyte proliferation, whereas SRC3 uniquely regulates the ability of 1,25(OH)2D3 to induce more differentiated functions such as lipid synthesis and processing required for permeability barrier formation and the innate immune response triggered by disruption of the barrier. These findings provide a basis by which we can understand how one receptor (VDR) and one ligand (1,25(OH)2D3) can regulate a large number of genes in a sequential and differentiation specific fashion. PMID- 20298786 TI - Neuroprotective effect of overexpression of thioredoxin on photoreceptor degeneration in Tubby mice. AB - The Tubby mouse is a phenotypic model for sensorineural deafness and retinal dystrophy including Usher syndrome type 1. Thioredoxin is a small 13kDa protein which, when ubiquitously expressed as a transgene in the mouse, provides protection against multiple disease states including light-induced and oxidative stress-induced neurodegeneration and is down-regulated in the Tubby retina. We tested if overexpression of human thioredoxin in the Tubby mouse inhibits retinal degeneration and loss of visual function. Electroretinography, immunocytochemistry, quantitative histology, RT-PCR and Western blots were used to obtain data which showed that thioredoxin overexpression prevented loss of photoreceptors and retinal function. Analysis of signal pathways showed that thioredoxin up-regulated neurotrophic factors BDNF and GDNF and activated survival signaling pathways Akt, Ras/Raf1/ and the ERKs while inhibiting the ASK1/JNK apoptosis pathway. Relationships between the Tubby gene, its pathological phenotype and regulation of the thioredoxin system remain to be established. PMID- 20298787 TI - Expression by midbrain dopamine neurons of Sema3A and 3F receptors is associated with chemorepulsion in vitro but a mild in vivo phenotype. AB - Here we explore the role of semaphorin 3A and 3F (Sema3A, Sema3F) in the formation of the mesotelencephalic pathway. We show that Sema3A and 3F are expressed in the ventral mesencephalon (VM) of E13.5 rat embryos; the receptors Neuropilin 1 and Neuropilin 2, and co-receptors L1CAM, NrCAM, and Plexins A1 and A3 but not A4 are expressed by VM dopaminergic neurons; these neurons bind Sema3A and 3F in vitro which induces collapse of their growth cones and elicits, with different potencies, a repulsive response; and this response is absent in axons from Nrp1 and Nrp2 null embryos. Despite these in vitro effects, only very mild anatomical defects were detected in the organization of the mesotelencephalic pathway in embryonic and adult Nrp1 or Nrp2 null mice. However, the dopaminergic meso-habenular pathway and catecholaminergic neurons in the parafascicular and paraventricular nuclei of the thalamus were significantly affected in Nrp2 null mice. These data are consistent with a model whereby Sema3A and 3F, in combination with other guidance molecules, contributes to the navigation of DA axons to their final synaptic targets. PMID- 20298788 TI - Balanced Vav2 GEF activity regulates neurite outgrowth and branching in vitro and in vivo. AB - We have investigated the role of Vav2, a reported Rac1/Cdc42 GEF, on the development of Xenopus spinal neurons in vitro and in vivo. Both gain and loss of Vav2 function inhibited the rate neurite extension on laminin (LN), while only GFP-Vav2 over-expression enhanced process formation and branching. Vav2 over expression protected neurons from RhoA-mediated growth cone collapse, similar to constitutively active Rac1, suggesting that Vav2 activates Rac1 in spinal neurons. Enhanced branching on LN required both Vav2 GEF activity and N-terminal tyrosine residues, but protection from RhoA-mediated collapse only required GEF activity. Interestingly, wild-type spinal neurons exhibited increased branching on the cell adhesion molecule L1, which required Vav2 GEF function, but not N terminal tyrosine residues. Finally, we find that Vav2 differentially affects the Rohon-Beard peripheral and central process extension but promotes neurite branching of commissural interneurons near the ventral midline. Together, we suggest that balanced Vav2 activity is necessary for optimal neurite outgrowth and promotes branching by targeting GEF activity to branch points. PMID- 20298789 TI - Molecular cloning and characterization of interferon regulatory factors 4 and 8 (IRF-4 and IRF-8) in rainbow trout, Oncorhynchus mykiss. AB - Mammalian interferon regulatory factor (IRF)4 (PIP, LSIRF, and ICSAT) and IRF8 (ICSBP) are known to be critical in regulating a spectrum of functional and developmental processes in lymphomyeloid cell lineages either through direct binding to IRF-E motifs in target gene promoters or indirectly by binding to composite motifs recognized by Ets family members, PU.I and Sp.I. Here we report, for the first time in fish, the sequencing and characterization of full-length cDNA homologues of rainbow trout (rt) IRF4 and rtIRF8. The rtIRF4 molecule consists of 1848 bp with a 45 bp 5' UTR and a predicted 378 bp 3' UTR translating into a 474 aa protein. RtIRF8 consists of 1951 bp with a 52 bp 5' UTR and a 564 bp 3' UTR translating into a 444 aa protein. Each gene possesses a putative DNA binding domain (DBD) containing the tryptophan pentad-repeat domain found in all IRF family members. Both molecules also possess a well conserved IRF association domain (IAD). The presence of these domains along with phylogenetic analysis places the two genes in the IRF4 subfamily. Both genes were detected in a range of trout tissues where IRF8 was the overall predominant transcript. Consistent with mammalian studies, the highest expression levels of IRF4 and IRF8 were observed in the lymphomyeloid-rich fish tissues, spleen, head kidney and gills. IRF8 expression in stimulated trout splenocytes was significantly up-regulated by polyinosinic:polycytidylic acid (poly I:C), trout recombinant (r)IL-15, phorbol 12-myristate 13-acetate (PMA), and phytohaemagglutinin (PHA) treatment whilst remaining refractory towards lipopolysaccharide (LPS) treatment. IRF4 was significantly down-regulated by LPS stimulation and remained refractory towards poly I:C, trout rIL15, and PHA. PMA stimulation elicited a significant upregulation of IRF4 expression. Overall, these data support the premise that these IRFs are likely to play important roles in the functional and developmental processes occurring in fish lymphomyeloid tissues. PMID- 20298790 TI - Trajectories of brain aging in middle-aged and older adults: regional and individual differences. AB - The human brain changes with age. However, the rate and the trajectories of change vary among the brain regions and among individuals, and the reasons for these differences are unclear. In a sample of healthy middle-aged and older adults, we examined mean volume change and individual differences in the rate of change in 12 regional brain volumes over approximately 30 months. In addition to the baseline assessment, there were two follow-ups, 15 months apart. We observed significant average shrinkage of the hippocampus, entorhinal cortex, orbital frontal cortex, and cerebellum in each of the intervals. Shrinkage of the hippocampus accelerated with time, whereas shrinkage of the caudate nucleus, prefrontal subcortical white matter, and corpus callosum emerged only at the second follow-up. Throughout both assessment intervals, the mean volumes of the lateral prefrontal and primary visual cortices, putamen, and pons did not change. Significant individual differences in shrinkage rates were observed in the lateral prefrontal cortex, the cerebellum, and all the white matter regions throughout the study, whereas additional regions (medial-temporal structures, the insula, and the basal ganglia) showed significant individual variation in change during the second follow-up. No individual variability was noted in the change of orbital frontal and visual cortices. In two white matter regions, we were able to identify factors associated with individual differences in brain shrinkage. In corpus callosum, shrinkage rate was greater in persons with hypertension, and in the pons, women and carriers of the ApoEepsilon4 allele exhibited declines not noted in the whole sample. PMID- 20298791 TI - Auditory temporal expectations modulate activity in visual cortex. AB - Temporal expectation is the ability to make predictions and to use temporal information to anticipate the occurrence of future events. This capacity is associated with highly efficient perceptual and motor behaviors. However, how cognitive systems use temporal information to optimize behavior and what brain structures are engaged during these processes remains largely unknown. Neurophysiological and recent neuroimaging data have suggested that temporal expectations modulate activity not only in parietal and motor-related frontal regions, but also in occipital visual cortex, when the expected stimulus is a simple visual object. Here we investigate crossmodal properties and category selectivity of temporal expectations examining activity in visual cortex during expectation of auditory stimuli (the sound of hand-clapping or of a hammer hammering). We found that activity in occipital cortex changed over time, reflecting the subject's temporal expectations about the upcoming auditory event. This modulatory effect included extrastriate visual areas known to process body parts and tools, despite these were never presented visually during the experiment. However activity in these areas was not specific for the expected sound category, but it was rather related to the overall probability of the auditory target to occur. We conclude that crossmodal associations can influence activity in sensory-specific visual areas in an anticipatory manner, consistent with temporal expectations affecting activity in a distributed system of motor related and sensory-related brain regions. PMID- 20298793 TI - Heritability of DTI and MTR in nine-year-old children. AB - Overall brain size is strikingly heritable throughout life. The influence of genes on variation in focal gray and white matter density is less pronounced and may vary with age. This paper describes the relative influences of genes and environment on variation in white matter microstructure, measured along fiber tracts with diffusion tensor imaging and magnetization transfer imaging, in a sample of 185 nine-year old children from monozygotic and dizygotic twin pairs. Fractional anisotropy, a measure of microstructural directionality, was not significantly influenced by genetic factors. In contrast, studying longitudinal and radial diffusivity separately, we found significant genetic effects for both radial and longitudinal diffusivity in the genu and splenium of the corpus callosum and the right superior longitudinal fasciculus. Moreover, genetic factors influencing the magnetization transfer ratio (MTR), putatively representing myelination, were most pronounced in the splenium of the corpus callosum and the superior longitudinal fasciculi, located posterior in the brain. The differences in the extent to which genetic and environmental factors influence the various diffusion parameters and MTR, suggest that different physiological mechanisms (either genetic or environmental) underlie these traits at nine years of age. PMID- 20298792 TI - Increased functional brain response during word retrieval in cognitively intact older adults at genetic risk for Alzheimer's disease. AB - Recent language studies in aging and dementia provide two complementary lines of evidence that: (1) measures of semantic knowledge and word-finding ability show declines comparable to those of episodic memory, and greater impairment than executive function measures, during the prodromal period of Alzheimer's disease and (2) cognitively intact older adult carriers of the apolipoprotein E (APOE) epsilon4 allele also demonstrate poorer object naming than their low-risk peers. Given that possible changes in the neural substrates of word retrieval (e.g., Broca's area and fusiform gyrus) in at-risk adults may signal impending cognitive decline and serve as a prodromal marker of AD, we examined whether APOE epsilon4 carriers exhibit changes in brain response in regions subserving word retrieval and semantic knowledge. Eleven cognitively intact APOE epsilon4 older adults and 11 age, education, and family history of AD-matched APOE epsilon3 adults named aloud photographs of animals, tools, and vehicles during event-related fMRI. Results showed that, in the face of equivalent naming accuracy, APOE epsilon4 adults demonstrated more widespread brain response with greater signal change in the left fusiform gyrus, bilateral medial prefrontal cortex, and right perisylvian cortex. Findings are discussed in the context of possible compensatory mechanisms invoked to maintain performance in those at genetic risk for AD. PMID- 20298794 TI - Age-related changes in neural volume and microstructure associated with interleukin-6 are ameliorated by a calorie-restricted diet in old rhesus monkeys. AB - Systemic levels of proinflammatory cytokines such as interleukin-6 (IL-6) increase in old age and may contribute to neural atrophy in humans. We investigated IL-6 associations with age in T1-weighted segments and microstructural diffusion indices using MRI in aged rhesus monkeys (Macaca mulatta). Further, we determined if long-term 30% calorie restriction (CR) reduced IL-6 and attenuated its association with lower tissue volume and density. Voxel-based morphometry (VBM) and diffusion-weighted voxelwise analyses were conducted. IL-6 was associated with less global gray and white matter (GM and WM), as well as smaller parietal and temporal GM volumes. Lower fractional anisotropy (FA) was associated with higher IL-6 levels along the corpus callosum and various cortical and subcortical tracts. Higher IL-6 concentrations across subjects were also associated with increased mean diffusivity (MD) throughout many brain regions, particularly in corpus callosum, cingulum, and parietal, frontal, and prefrontal areas. CR monkeys had significantly lower IL-6 and less associated atrophy. An IL-6xCR interaction across modalities also indicated that CR mitigated IL-6 related changes in several brain regions compared to controls. Peripheral IL-6 levels were correlated with atrophy in regions sensitive to aging, and this relationship was decreased by CR. PMID- 20298795 TI - Fructanolytic and saccharolytic enzymes of Treponema zioleckii strain kT. AB - Enzymes in the newly described rumen bacterium, Treponema zioleckii strain kT, capable of digesting Timothy grass fructan, inulin, and sucrose were identified and characterized. Two specific endolevanases and one non-specific beta fructofuranosidase were found in a cell-free extract. The molecular weight of the endolevanases were estimated to be 60 and 36 kDa, whereas that of beta fructofuranosidase, 87 kDa. The former of the specific enzymes was associated with the outer membrane, while the latter and the non-specific beta fructofuranosidase, with the periplasm or cytosol. The K(m) and V(max) for Timothy grass fructan degradation by endolevanase were 0.27% and 15.75 microM fructose equivalents x mg protein(-1) x min(-1), those for sucrose and inulin digestion by beta-fructofuranosidase were 1.35 x 10(-3)M and 1.73 microM hexoses x mg protein(-1) x min(-1) and 1.77% and 1.83 microM hexoses x mg protein(-1) x min(-1), respectively. PMID- 20298796 TI - Microbial equol production attenuates colonic methanogenesis and sulphidogenesis in vitro. AB - Hydrogen gas produced during colonic fermentation is excreted in breath and flatus, or removed by hydrogen-consuming bacteria such as methanogens and sulphate-reducing bacteria. However, recent research has shown that H2 is also consumed by equol-producing bacteria during the reduction of daidzein into equol. In this study, the interactions between methanogens, sulphate-reducing, and equol producing bacteria were investigated under in vitro simulated intestinal conditions. In the presence of daidzein, the equol-producing bacterial consortium EPC4 gave rise to equol production in cultures of Methanobrevibacter smithii or Desulfovibrio sp. as well as in faecal samples with methanogenic or sulphate reducing abilities. Moreover, this supplementation significantly (P<0.001) decreased the methanogenesis and sulphidogenesis. The attenuation did not occur in the absence of a daidzein source. Additionally, there was no influence of soy germ powder, daidzein or equol as such, excluding a possible inhibition by these compounds. Finally, a stronger decrease was observed with increasing amounts of EPC4 and a constant equol production, suggesting that the observed effect was only partly caused by the action of daidzein as a hydrogen sink. These findings are of relevance since abdominal discomfort such as bloating and flatulence, are related to colonic gas production, whereas equol has potential health benefits. PMID- 20298797 TI - Blood chemistry in white stork Ciconia ciconia chicks varies by sex and age. AB - Little is known on how blood biochemistry differs among avian chicks, especially in sexually monomorphic species. In this study we sampled blood chemistry of 342 white stork Ciconia ciconia chicks from nests in western Poland during four years (2005-2008). Special attention was paid to the effect of chick age and sex on blood biochemistry. Since white stork is a monomorphic species, the sex of chicks was established by a molecular technique. Nine blood biochemical parameters were studied: total protein concentration, urea, uric acid, triglycerides, total cholesterol, high density lipoprotein cholesterol (HDL), low density lipoprotein cholesterol (LDL), aspartate aminotransferase (AST) and alanine aminotransferase (ALT). There were sexual differences in total protein, uric acid, cholesterol, HDL and AST. However, total protein and uric acid only differed significantly between sexes if an age effect was included as a covariate in the analysis. Triglycerides decreased significantly, and AST, increased significantly with chick age. We confirm that blood biochemistry varies with chick age, but we also found significant differences between the sexes. Therefore, to understand changes in blood parameters, and to establish reference ranges useful in captive rearing of this endangered species, establishing gender may be important, even in very young individuals. PMID- 20298799 TI - Pharmacogenetics--pivotal to the future of the biopharmaceutical industry. PMID- 20298798 TI - Activation of the P2X(7) receptor triggers the elimination of Toxoplasma gondii tachyzoites from infected macrophages. AB - Toxoplasmosis is caused by the protozoan parasite Toxoplasma gondii, which is widespread throughout the world. After active penetration, the parasite is enclosed within a parasitophorous vacuole and survives in the host cell by avoiding, among other mechanisms, lysosomal degradation. A large number of studies have demonstrated the importance of ATP signalling via the P2X(7) receptor, as a component of the inflammatory response against intracellular pathogens. Here we evaluate the effects of extracellular ATP on T. gondii infection of macrophages. ATP treatment inhibits the parasite load and the appearance of large vacuoles in the cytoplasm of intracellular parasites. ROS and NO assays showed that only ROS production is involved with the ATP effects. Immunofluorescence showed colocalization of Lamp1 and SAG1 only after ATP treatment, suggesting the formation of phagolysosomes. The involvement of P2X(7) receptors in T. gondii clearance was confirmed by the use of P2X(7) agonists and antagonists, and by infecting macrophages from P2X(7) receptor-deficient mice. We conclude that parasite elimination might occur following P2X(7) signalling and that novel therapies against intracellular pathogens could take advantage of activation of purinergic signalling. PMID- 20298800 TI - Use of Benford's law in drug discovery data. AB - Benford's law states that the distribution of the first digit of many data sets is not uniform. The first digit of any random number will be 1 almost 30% of the time, and larger digits occur as the first digit with lower and lower frequency, to the point where 9 occurs as a first digit only 5% of the time. Here, we demonstrate that several data sets in the field of drug discovery follow Benford's distribution, whereas 'doctored' data do not. Our findings indicate the applicability of Benford's law in assessing data quality in the field of drug discovery. We also propose a useful index of evaluating data quality based on Benford's law. PMID- 20298801 TI - New therapies to treat sight loss in an ageing population. PMID- 20298802 TI - Complex exchanges are responsible for the increased effectiveness of C-ions compared to X-rays at the first post-irradiation mitosis. AB - The purpose of the present study was to investigate as to what extent differences in the linear energy transfer (LET) are reflected at the chromosomal level. For this study human lymphocytes were exposed to 9.5 MeV/u C-ions (1 or 2 Gy, LET=175 keV/microm) or X-rays (1-6 Gy), harvested at 48, 72 or 96 h post-irradiation and aberrations were scored in first cycle metaphases using 24 color fluorescence in situ hybridization (mFISH). Additionally, in selected samples aberrations were measured in prematurely condensed G2-phase cells. Analysis of the time-course of aberrations in first cycle metaphases showed a stable yield of simple and complex exchanges after X-ray irradiation. In contrast, after C-ion exposure the yields profoundly increased with harvesting time complicating the estimation of the frequency of aberrations produced by high LET particles within the entire cell population. This is especially true for the yield of complex exchanges. Complex aberrations dominate the aberration spectrum produced by C-ions. Their fraction was about 50% for the two measured doses. In contrast, isodoses of X-rays induced smaller proportions of complex aberrations (i.e. 5% and 15%, respectively). For both radiation qualities the fraction of complexes did not change with harvesting time. As expected from the different dose deposition of high and low LET radiation, complex exchanges produced by high LET C-ions involved more breaks and more chromosomes than those induced by isodoses of X-rays. Noteworthy, C-ions but not X-rays induced a small number of complex chromatid-isochromatid exchanges that are not expected for cells exposed in the G0-phase. The results obtained so far for cells arrested in G2-phase confirm these patterns. Altogether our data show that the increased effectiveness of C-ions for the induction of aberrations in first cycle cells is determined by complex exchanges, whereas for simple exchanges the relative biological effectiveness is about one. PMID- 20298803 TI - Some unsolved problems and unresolved issues in radiation cytogenetics: a review and new data on roles of homologous recombination and non-homologous end joining. AB - New data and historical evidence from our own and other laboratories are summarized and discussed bearing on several issues relating to mechanisms and processes involved in the formation of chromosomal aberrations following exposure to ionizing radiations. Specifically addressed are: (1) the lesions and processes affecting the appearance of chromatid-type and/or chromosome-type aberrations after radiation, (2) DNA double strand break rejoining processes and the restitution of breaks vs. the formation of exchanges, (3) the role of homologous recombinational repair in protecting cells from induction of chromatid-type aberrations after irradiation of late S/G2 cells, (4) the role of interphase chromatin structure and nuclear organization in aberration induction, (5) cellular responses for aberration induction in relation to their tissue context, and (6) approaches to the detection of aberrations previously known as "cryptic". PMID- 20298804 TI - Comparison of different cytotoxicity measurements for the in vitro micronucleus assay using L5178Y and TK6 cells in support of OECD draft Test Guideline 487. AB - The reference genotoxic agents mitomycin C, cadmium chloride, 2-aminoanthracene, vinblastine sulphate and 5-fluorouracil were tested in the in vitro micronucleus assay, in mouse lymphoma L5178Y cells and in human lymphoblastoid cells TK6, without cytokinesis block. This was done in support of the toxicity measures recommended in the late 2007 version of the draft OECD Test Guideline 487 for the testing of chemicals. Relative Population Doubling and Relative Increase in Cell Counts, used for the selection of the highest concentrations to be evaluated for genotoxicity assessment, based on a 50+/-5% cytotoxicity, both allowed to equally detect positive mitomycin C, cadmium chloride, 2-aminoanthracene, vinblastine sulphate and 5-fluorouracil on L5178Y and/or TK6 cells. Therefore, these parameters, recommended in the draft Test Guideline 487, are suitable to select the concentrations at the cytotoxicity required for genotoxicity assessment in the in vitro micronucleus assay without cytokinesis block. PMID- 20298805 TI - Relationship between chromatin structure, DNA damage and repair following X irradiation of human lymphocytes. AB - Earlier studies using the technique of premature chromosome condensation (PCC) have shown that in human lymphocytes, exchange type of aberrations are formed immediately following low doses (<2 Gy) of X-rays, whereas at higher doses these aberrations increase with the duration of recovery. This reflects the relative roles of slow and fast repair in the formation of exchange aberrations. The underlying basis for slow and fast repairing components of the DNA repair may be related to differential localization of the initial damage in the genome, i.e., between relaxed and condensed chromatin. We have tried to gain some insight into this problem by (a) X-irradiating lymphocytes in the presence of dimethyl sulfoxide (DMSO) a potent scavenger of radiation-induced .OH radicals followed by PCC and (b) probing the damage and repair in two specific chromosomes, 18 and 19, which are relatively poor and rich in transcribing genes by COMET-FISH, a combination of Comet assay and fluorescence in situ hybridization (FISH) techniques. Results obtained show (a) that both fast appearing and slowly formed exchange aberrations seem to take place in relaxed chromatin, since they are affected to a similar extent by DMSO, (b) significant differential DNA breakage of chromosome 18 compared to chromosome 19 in both G0 and G1 phases of the cell cycle as detected by Comet assay, indicating that relaxed chromatin containing high densities of transcriptionally active genes shows less fragmentation due to fast repair (chromosome 19) compared to chromosome 18, and (c) that relaxed chromatin is repaired or mis-repaired faster than more compact chromatin. PMID- 20298808 TI - Gelucire 44/14 improves fat absorption in rats with impaired lipolysis. AB - Clinically relevant fat malabsorption is usually due to impaired intestinal fat digestion (lipolysis) and/or to impaired solubilization of the lipolytic metabolites. We hypothesized that Gelucire 44/14 - a semi-solid self-micro emulsifying excipient - could increase fat absorption. In relevant rat models for impaired lipolysis or for impaired solubilization we tested whether administration of Gelucire 44/14 enhanced fat absorption. Rats with impaired lipolysis (lipase inhibitor Orlistat diet) and rats with reduced solubilization (permanent bile diversion) underwent a 72 h fat balance test to assess fat absorption. The absorption kinetics of a stable isotope-labeled fatty acid was assessed in rats with reduced solubilization, in the presence or absence of Gelucire 44/14. Gelucire 44/14 improved fat absorption in rats with impaired lipolysis (from 70% to 82%, p<0.001). In rats with reduced solubilization, Gelucire 44/14 did not increase fat absorption nor did it reconstitute the absorption kinetics of (13)C-labeled palmitate, compared with control rats administered buffer without Gelucire 44/14. The present data show that Gelucire 44/14 might enhance fat absorption under conditions of impaired lipolysis, but not during impaired solubilization. We speculate that, due to its self-micro emulsification properties, Gelucire 44/14 stabilizes and improves residual lipolytic enzyme activity in vivo, which could be of therapeutic value in clinical conditions of fat malabsorption due to impaired lipolysis. PMID- 20298807 TI - Marked variability in hepatic expression of cytochromes CYP7A1 and CYP27A1 as compared to cerebral CYP46A1. Lessons from a dietary study with omega 3 fatty acids in hamsters. AB - Two diets simulating the recommendations of the American Heart Association to increase the intake of n-3 polyunsaturated fatty acids (n-3 PUFAs) were tested on Golden Syrian hamsters and compared to the diet simulating the current estimated consumption of fat in the United States. N-3 PUFAs were evaluated for their effects on serum and brain lipids and on the three cytochrome P450 enzymes (CYPs 7A1, 27A1, and 46A1) that play key roles in cholesterol elimination from different organs. Hamsters on the highest concentration of n-3 PUFAs had a statistically significant decrease in LDL and HDL cholesterol and no change in serum total cholesterol and triglycerides levels. CYP27A1 and CYP46A1 mRNA levels were increased in the liver and brain, respectively, whereas possible effects on CYP7A1 were obscured by a marked intergroup variability at mRNA, protein, and sterol product levels. Increased levels of CYP46A1 mRNA in the brain did not lead to significant changes in the levels of lathosterol, 24S-hydroxycholesterol or cholesterol in this organ. The data obtained are discussed in relation to inconsistent effects of n-3 PUFAs on serum lipids in human trials and reported positive effects of fish oil on cognitive function. PMID- 20298809 TI - Effects of monocrotophos on the reproductive axis in the female goldfish (Carassius auratus). AB - Monocrotophos (MCP) is a highly toxic organophosphorus pesticide. To elucidate the influence of MCP on female fish reproduction, plasma 17beta-estradiol, testosterone and gonadotropin levels and aromatase and gonadotropin beta subunit gene expression levels were examined in female goldfish (Carassius auratus) following a 21-day exposure to 0.01, 0.10 and 1.00 mg L-(1) 40% MCP-based pesticide in a semi-static exposure system. The results indicated that MCP induced increases in plasma 17beta-estradiol levels and the 17beta estradiol/testosterone ratio via interference with the reproductive axis at multiple potential sites through two mechanisms: (a) MCP exposure enhanced the mRNA expression of gonadal aromatase, the enzyme that converts androgens into estrogens, consequently reducing plasma testosterone levels and increasing plasma concentrations of 17beta-estradiol; and (b) MCP treatment increased follicle stimulating hormone beta subunit mRNA expression and secretion and decreased luteinizing hormone beta subunit mRNA expression and secretion, leading to the disruption of reproductive endocrine control and androgen and estrogen balance. This study provided convincing evidence for reproductive toxicology of MCP by disrupting of the HPG axis at multiple sites in female goldfish. PMID- 20298806 TI - Mechanisms of intestinal inflammation and development of associated cancers: lessons learned from mouse models. AB - Chronic inflammation is strongly associated with approximately 1/5th of all human cancers. Arising from combinations of factors such as environmental exposures, diet, inherited gene polymorphisms, infections, or from dysfunctions of the immune response, chronic inflammation begins as an attempt of the body to remove injurious stimuli; however, over time, this results in continuous tissue destruction and promotion and maintenance of carcinogenesis. Here we focus on intestinal inflammation and its associated cancers, a group of diseases on the rise and affecting millions of people worldwide. Intestinal inflammation can be widely grouped into inflammatory bowel diseases (ulcerative colitis and Crohn's disease) and celiac disease. Long-standing intestinal inflammation is associated with colorectal cancer and small-bowel adenocarcinoma, as well as extraintestinal manifestations, including lymphomas and autoimmune diseases. This article highlights potential mechanisms of pathogenesis in inflammatory bowel diseases and celiac disease, as well as those involved in the progression to associated cancers, most of which have been identified from studies utilizing mouse models of intestinal inflammation. Mouse models of intestinal inflammation can be widely grouped into chemically induced models; genetic models, which make up the bulk of the studied models; adoptive transfer models; and spontaneous models. Studies in these models have lead to the understanding that persistent antigen exposure in the intestinal lumen, in combination with loss of epithelial barrier function, and dysfunction and dysregulation of the innate and adaptive immune responses lead to chronic intestinal inflammation. Transcriptional changes in this environment leading to cell survival, hyperplasia, promotion of angiogenesis, persistent DNA damage, or insufficient repair of DNA damage due to an excess of proinflammatory mediators are then thought to lead to sustained malignant transformation. With regards to extraintestinal manifestations such as lymphoma, however, more suitable models are required to further investigate the complex and heterogeneous mechanisms that may be at play. PMID- 20298810 TI - Emodin and rhein inhibit LIGHT-induced monocytes migration by blocking of ROS production. AB - LIGHT is known to act as a novel mediator for atherogenesis. Furthermore, it has been reported that emodin, an active component extracted from rhubarb, can stop the growth of cancer cells. However, it is not known if emodin exerts anti atherogenic effects in the human monocyte, THP-1, following treatment with LIGHT. In this study, we evaluated the inhibitory effect of emodin and rhein on LIGHT induced migration in THP-1. Emodin and rhein decreased the level of LIGHT-induced generation of ROS, as well as the expression of CCR1, CCR2 and ICAM-1 and the production of IL-8, MCP-1, TNF-alpha, and IL-6. Emodin and rhein also decreased the phosphorylation of the p38 MAPK and IkB-alpha. Furthermore, the NADPH oxidase assembly inhibitor, AEBSF, and the blocker of NADPH oxidase, p47(phox) small interference RNA (siRNA), also efficiently blocked LIGHT-induced migration, CCR1, CCR2, ICAM-1, and HVEM expression, and p38 MAPK and NF-kB activation. These findings indicate that the inhibitory effects of emodin and rhein on LIGHT induced migration occur via decreasing ROS production and NADPH oxidase p47(phox) activation. Taken together, these results indicate that emodin and rhein have the potential for use as an anti-atherosclerosis agent. PMID- 20298811 TI - Hepatitis B virus DNA level predicts hepatic decompensation in patients with acute exacerbation of chronic hepatitis B. AB - BACKGROUND & AIMS: Acute exacerbations of chronic hepatitis B virus (HBV) infection can lead to hepatic decompensation. It is important to identify factors that predict the development of hepatic decompensation during exacerbation so that antiviral therapy can be initiated immediately. METHODS: Acute exacerbation, defined by an abrupt increase in alanine aminotransferase (ALT) levels to >5-fold the upper limit of normal, occurred in 110 hepatitis B e antigen (HBeAg) seropositive non-cirrhotic patients (138 episodes). The patients were monitored every 1 to 2 weeks for serum levels of ALT, bilirubin, albumin, and prothrombin. Sex, age, HBV genotype, ALT level, HBV viral load, and the causes (spontaneous or relapse from antiviral treatment) of exacerbation were included in multivariate logistic regression analyses. The receiver operating characteristic curve was used to identify the optimal cut-off value of serum HBV DNA level to identify patients at risk for decompensation. RESULTS: Seven of the 138 episodes of acute exacerbation (5.1%) resulted in hepatic decompensation; serum HBV DNA level was the only significant risk factor (P = .003). The area under the receiver operating characteristic curve was 88.6% (P < .001). A serum HBV DNA cut-off value of 1.55 x 10(9) copies/mL predicted decompensation with a sensitivity of 85.7%, a specificity of 85.5%, a negative prediction value of 99.1%, and positive prediction value of 24.0%. CONCLUSIONS: During acute exacerbation of HBeAg positive chronic hepatitis B, a serum HBV DNA cut-off value of 1.55 x 10(9) copies/mL can be used to identify patients in need of immediate antiviral therapy. PMID- 20298812 TI - A simulation-based comparison of the traditional method, Rolling-6 design and a frequentist version of the continual reassessment method with special attention to trial duration in pediatric Phase I oncology trials. AB - The traditional method (TM), also known as the 3+3 up-and-down design, and the continual reassessment method (CRM) are commonly used in Phase I oncology trials to identify the maximum tolerated dose (MTD). The rolling-6 is a relative newcomer which was developed to shorten trial duration by minimizing the period of time during which the trial is closed to accrual for toxicity assessment. In this manuscript we have compared the performance of these three approaches via simulations not only with respect to the usual parameters such as overall toxicity, sample size and percentage of patients treated at doses above the MTD but also in terms of trial duration and the dose chosen as the MTD. Our results indicate that the toxicity rates are comparable across the three designs, but the TM and the rolling-6 tend to treat a higher percentage of patients at doses below the MTD. With respect to trial duration, rolling-6 leads to shorter trials compared to the TM but not compared to the CRM. Additionally, the doses identified as the MTD by the TM and the rolling-6 differ in a large percentage of trials. Our results also indicate that the body surface area-based dosing used in pediatric trials can make a difference in dose escalation/de-escalation patterns in the CRM compared to the cases where such variations are not taken into account in the calculations, even leading to different MTDs in some cases. PMID- 20298813 TI - Immunological tolerance induced by galectin-1 in rat allogeneic renal transplantation. AB - OBJECTIVES: The existed literatures indicated that galectin-1 has anti inflammatory effects and plays a pivotal role in autoimmune diseases. Present study was to identify the roles of galectin-1 in acute animal renal allograft rejection. METHODS: Rat acute rejection models were erected by allogeneic renal transplantation. Galectin-1 injection was performed in different concentrations in renal recipients post-transplantation. Recipient survivals, CD8+ T cell proliferation, production of IFN-gamma, levels of serum CD30, enzyme-linked immunoabsorbent spot assay (ELISPOT) and immunohistochemistry were observed or tested 7days after renal transplantation. RESULTS: Galectin-1 injection can prolong the recipient animal survival, reduce the serum levels of IFN-gamma, soluble CD30, percentage of CD8+ T cell subset, CD8+ T cell-mediated cytotoxicity, and IFN-gamma ELISPOT frequency for allograft recipients. The therapeutic effects of galectin-1 injection on recipient rats were dose dependent. CONCLUSION: Galectin-1 plays an important role in CD8+ T cell-mediated renal rejection by inducing immunological tolerance. PMID- 20298814 TI - Respiratory Physiology & Neurobiology. Editorial. PMID- 20298815 TI - Effect of propofol on breathing stability in adult ICU patients with brain damage. AB - The aim of the study was to investigate Propofol's effect on breathing stability in brain damage patients, as quantified by the Loop Gain (LG) of the respiratory system (breathing stability increases with decreasing LG). In 11 stable brain damage patients full polysomnography was performed before, during and after propofol sedation, titrated to achieve stage 2 or slow wave sleep. During each period, patients were ventilated with proportional assist ventilation and the % assist was increased in steps, until either periodic breathing (PB) occurred or the highest assist (95%) was achieved. The tidal volume amplification factor (VT(AF)) at the highest assist level reached just before PB occurred was used to calculate LG (LG=1/VT(AF)). In all but one patient, PB was observed. With propofol, the assist level at which PB occurred (73 + or - 19%) was significantly higher, than that before (43 + or - 35%) and after propofol sedation (49 + or - 29%). As a result, with propofol LG (0.49 + or - 0.2) was significantly lower than that before (0.74 + or - 0.2) and after propofol sedation (0.69 + or - 0.2) (p<0.05). We conclude that Propofol decreases LG. Therefore it exerts an overall stabilizing effect on control of breathing. PMID- 20298816 TI - Differential scanning calorimetry and fluorescence study of lactoperoxidase as a function of guanidinium-HCl, urea, and pH. AB - The stability of bovine lactoperoxidase to denaturation by guanidinium-HCl, urea, or high temperature was examined by differential scanning calorimetry (DSC) and tryptophan fluorescence. The calorimetric scans were observed to be dependent on the heating scan rate, indicating that lactoperoxidase stability at temperatures near Tm is controlled by kinetics. The values for the thermal transition, Tm, at slow heating scan rate were 66.8, 61.1, and 47.2 degrees C in the presence of 0.5, 1, and 2 M guanidinium-HCl, respectively. The extrapolated value for Tm in the absence of guanidinium-HCl is 73.7 degrees C, compared with 70.2 degrees C obtained by experiment; a lower experimental value without a denaturant is consistent with distortion of the thermal profile due to aggregation or other irreversible phenomenon. Values for the heat capacity, Cp, at Tm and Ea for the thermal transition decrease under conditions where Tm is lowered. At a given concentration, urea is less effective than guanidinium-HCl in reducing Tm, but urea reduces Cp relatively more. Both fluorescence and DSC indicate that thermally denatured protein is not random coil. A change in fluorescence around 35 degrees C, which was previously reported for EPR and CD measurements (Boscolo et al. Biochim. Biophys. Acta 1774 (2007) 1164-1172), is not seen by calorimetry, suggesting that a local and not a global change in protein conformation produces this fluorescence change. PMID- 20298817 TI - Aquifex aeolicus FlgM protein exhibits a temperature-dependent disordered nature. AB - Studies on the nature and function of intrinsically disordered proteins (IDP) over the past 10 years have demonstrated the importance of IDPs in normal cellular function. Although many proteins predicted to be IDPs have been experimentally characterized on an individual basis, the conservation of disorder between homologous proteins from different organisms has not been fully studied. We now demonstrate that the FlgM protein from the thermophile Aquifex aeolicus exhibits a more ordered conformation at 20 degrees C than the previously characterized FlgM protein from Salmonella typhimurium. FlgM is an inhibitor of the RNA transcription factor sigma28, which is involved in regulation of the late stage genes involved in flagella synthesis. Previous work has shown that the S. typhimurium FlgM protein is an intrinsically disordered protein, though the C terminus becomes ordered when bound to sigma28 or under crowded solution conditions. In this work, we demonstrate that at 20 degrees C the A. aeolicus FlgM protein exhibits alpha-helical character in circular dichroism (CD) experiments, though the percentage of alpha-helical content decreases with increased temperature, consistent with the FlgM assuming a less folded conformation. We also show that the A. aeolicus FlgM exhibits cooperativity in chemical denaturation experiments, consistent with a globular nature. Furthermore, we use the fluorescent probe FlAsH to show that the H2 helix is ordered, even in the unbound state and that the H1 and H2 helices appear to be associated with each other in the absence of the sigma28 protein. Finally, we demonstrate that the H2 helix assumes an extended conformation at 85 degrees C. Based on our results, we propose that at 20 degrees C the A. aeolicus FlgM assumes a four-helix bundle-like conformation that becomes a more extended conformation at the A. aeolicus' physiological temperature of 85 degrees C. PMID- 20298818 TI - Peak frequencies of circulating human influenza-specific antibody secreting cells correlate with serum antibody response after immunization. AB - Upon vaccination, B cells differentiate into antibody secreting cells (ASCs) that migrate via the circulation to tissues. The kinetics of this response and the relationship of circulating ASCs to protective antibody titers have not been completely explored. METHODS: Influenza-specific and total-IgG ASCs were enumerated by Elispot and flow cytometry daily in the blood in 6 healthy adults after trivalent influenza vaccination (TIV). RESULTS: Peak H1-specific IgG ASC frequencies occurred variably from day 5 to 8 and correlated with the fold-rise rise in hemagglutination inhibition (HAI titers); r=0.91, p=0.006. H3-specific IgG ASC frequencies correlated less well, perhaps due to a mismatch of the H3 protein in the vaccine and that used in the Elispot assay. Peak frequencies of vaccine-specific and total-IgG ASCs were 0.3% and 0.8%, respectively, of peripheral blood mononuclear cells (PBMC). Peak TIV-, H1-, H3-, and total-IgG ASC frequencies were 1736+/-1133, 626+/-520, 592+/-463, and 4091+/-2019 spots/10(6) PBMC, respectively. Peak TIV-, H1-, and H3-specific IgG ASC of total-IgG ASC frequencies constituted 63%+/-21, 26%+/-10, 22%+/-17, respectively. CONCLUSION: After immunization with inactivated influenza vaccine the peak in influenza specific ASC frequencies is variable but correlates well with the magnitude of protective HAI responses. PMID- 20298819 TI - Impact of segmental left ventricle lead position on cardiac resynchronization therapy outcomes. AB - BACKGROUND: The optimal pacing site for cardiac resynchronization therapy (CRT) is along the left ventricle (LV) lateral or posterolateral wall. However, little is known about the impact of segmental pacing site on outcomes. OBJECTIVE: We assessed the impact of segmental LV lead position on CRT outcomes. METHODS: Patients (n = 115) undergoing CRT were followed prospectively. Segmental LV lead position along the longitudinal axis (apical, midventricle, or basal) was determined retrospectively by examining coronary sinus (CS) venograms and chest X rays. The primary outcome was a combined endpoint of heart failure hospitalization, cardiac transplantation, or all-cause mortality. Secondary outcomes included change in New York Heart Association (NYHA) functional class and degree of LV reverse remodeling. RESULTS: Patients were divided into two groups based on LV lead position: apical (n = 25) and basal/midventricle (n = 90). The apical group was older (72.9 +/- 8.9 vs. 66.5 +/- 13.3 years; P = .010) and more likely to have ischemic cardiomyopathy (77% vs. 52%, P <.001). During a mean follow-up of 15.1 +/- 9.0 months, event-free survival was significantly lower in the apical group: 52% vs. 79%, hazard ratio [HR] 2.7 (95% confidence interval [CI] 1.5-5.5, P = .006). The adverse impact of apical lead placement remained significant after adjusting for clinical covariates: HR 2.3 (95% CI 1.1 4.8, P = .03). The apical group also experienced less improvement in NYHA functional class and less LV reverse remodeling. CONCLUSIONS: Apical LV lead placement is associated with worse CRT outcomes. Preferential positioning of LV leads in the basal/midventricle segments may improve outcomes. PMID- 20298820 TI - Efficacy of partial body weight-supported treadmill training compared with overground walking practice for children with cerebral palsy: a randomized controlled trial. AB - OBJECTIVE: To evaluate the efficacy of 9 weeks of twice-weekly partial body weight-supported treadmill training (PBWSTT) for children with cerebral palsy (CP) and moderate to severe walking difficulty compared with overground walking. DESIGN: Randomized controlled trial. SETTING: Metropolitan Specialist School for children with moderate to severe physical and/or intellectual disabilities. PARTICIPANTS: Thirty-four children classified level III or IV by the Gross Motor Function Classification System were recruited and randomly allocated to experimental or control groups. Of these, 26 (15 girls, 11 boys; mean age 10 y, 10 mo +/- 3 y, 11 mo [range, 5-18 y]) completed training and testing. INTERVENTIONS: Both groups completed 9 weeks of twice-weekly walking training. The experimental group completed PBWSTT, and the control group completed overground walking practice. MAIN OUTCOME MEASURES: Ten-meter walk test (self selected walking speed), 10-minute walk (walking endurance), School Function Assessment. RESULTS: The overground walking group showed a trend for an increase in the distance walked over 10 minutes (F=3.004, P=.097). There was no statistically significant difference in self-selected walking speed over 10 meters or in walking function in the school environment as measured by the School Function Assessment. CONCLUSIONS: PBWSTT is safe and feasible to implement in a special school setting; however, it may be no more effective than overground walking for improving walking speed and endurance for children with CP. Continued emphasis on progressive reduction of body weight support along with adding concurrent overground walking practice to a treadmill training protocol may increase the intensity of training and assist with carryover of improvements to overground walking. Treadmill training programs that include concurrent overground walking as an additional key feature of the training protocol need to be rigorously evaluated for children with CP. PMID- 20298821 TI - Transrectal ultrasound-guided transperineal botulinum toxin a injection to the external urethral sphincter for treatment of detrusor external sphincter dyssynergia in patients with spinal cord injury. AB - OBJECTIVE: To evaluate the effects of a single transrectal ultrasound (TRUS) guided transperineal injection of botulinum toxin A (BTX-A) to the external urethral sphincter (EUS) for treating detrusor external sphincter dyssynergia (DESD). DESIGN: Descriptive study. SETTING: Rehabilitation hospital affiliated with a medical university. PARTICIPANTS: Patients (N=18) with suprasacral spinal cord injury who had DESD confirmed on video-urodynamic study. INTERVENTIONS: A single dose of 100U BTX-A was applied into the EUS via TRUS-guided transperineal route injection. MAIN OUTCOME MEASURES: Maximal detrusor pressure, detrusor leak point pressure, integrated electromyography (iEMG), maximal pressure on static urethral pressure profilometry, and postvoiding residuals. RESULTS: There were significant reductions in iEMG (P=.008) and static (P=.012) and dynamic urethral pressure (P=.023), but not in detrusor pressure and detrusor leak-point pressure after treatment. Postvoiding residuals also significantly decreased in the first and second month after treatment (P<.012). CONCLUSIONS: TRUS-guided transperineal injection of BTX-A has beneficial effects in treating DESD. PMID- 20298822 TI - Utility of functional status for classifying community versus institutional discharges after inpatient rehabilitation for stroke. AB - OBJECTIVE: To evaluate the ability of patient functional status to differentiate between community and institutional discharges after rehabilitation for stroke. DESIGN: Retrospective cross-sectional design. SETTING: Inpatient rehabilitation facilities contributing to the Uniform Data System for Medical Rehabilitation. PARTICIPANTS: Patients (N=157,066) receiving inpatient rehabilitation for stroke from 2006 and 2007. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURE: Discharge FIM rating and discharge setting (community vs institutional). RESULTS: Approximately 71% of the sample was discharged to the community. Receiver operating characteristic curve analyses revealed that FIM total performed as well as or better than FIM motor and FIM cognition subscales in differentiating discharge settings. Area under the curve for FIM total was .85, indicating very good ability to identify persons discharged to the community. A FIM total rating of 78 was identified as the optimal cut point for distinguishing between positive (community) and negative (institution) tests. This cut point yielded balanced sensitivity and specificity (both=.77). CONCLUSIONS: Discharge planning is complex, involving many factors. Identifying a functional threshold for classifying discharge settings can provide important information to assist in this process. Additional research is needed to determine if the risks and benefits of classification errors justify shifting the cut point to weight either sensitivity or specificity of FIM ratings. PMID- 20298823 TI - Monitoring training progress during exercise training in cancer survivors: a submaximal exercise test as an alternative for a maximal exercise test? AB - OBJECTIVE: To examine the use of a submaximal exercise test in detecting change in fitness level after a physical training program, and to investigate the correlation of outcomes as measured submaximally or maximally. DESIGN: A prospective study in which exercise testing was performed before and after training intervention. SETTING: Academic and general hospital and rehabilitation center. PARTICIPANTS: Cancer survivors (N=147) (all cancer types, medical treatment completed > or =3 mo ago) attended a 12-week supervised exercise program. INTERVENTIONS: A 12-week training program including aerobic training, strength training, and group sport. MAIN OUTCOME MEASURES: Outcome measures were changes in peak oxygen uptake (Vo(2)peak) and peak power output (both determined during exhaustive exercise testing) and submaximal heart rate (determined during submaximal testing at a fixed workload). RESULTS: The Vo(2)peak and peak power output increased and the submaximal heart rate decreased significantly from baseline to postintervention (P<.001). Changes in submaximal heart rate were only weakly correlated with changes in Vo(2)peak and peak power output. Comparing the participants performing submaximal testing with a heart rate less than 140 beats per minute (bpm) versus the participants achieving a heart rate of 140 bpm or higher showed that changes in submaximal heart rate in the group cycling with moderate to high intensity (ie, heart rate > or =140 bpm) were clearly related to changes in VO(2)peak and peak power output. CONCLUSIONS: For the monitoring of training progress in daily clinical practice, changes in heart rate at a fixed submaximal workload that requires a heart rate greater than 140 bpm may serve as an alternative to an exhaustive exercise test. PMID- 20298824 TI - Ultrasound as a screening tool for proceeding with caudal epidural injections. AB - OBJECTIVE: To study the anatomical structure of the sacral hiatus using ultrasound. Based on the sonographic images of the sacral hiatus, the feasibility of caudal epidural injection can then be assessed. DESIGN: Case-controlled study. SETTING: Rehabilitation outpatient clinic in a tertiary medical center. PARTICIPANTS: Patients (N=47; 20 women, 27 men) with low back pain and sciatica who were to receive caudal epidural injection treatments were recruited into this study. INTERVENTIONS: Sonographic images of the sacral hiatus were obtained from all the patients. An ultrasound machine capable of examining musculoskeletal tissues with real-time linear-array ultrasound transducer was used to measure the distance between the anterior wall and posterior wall of the sacral hiatus (diameter of the sacral hiatus) and the distance between bilateral cornua. MAIN OUTCOME MEASURES: Diameter of the sacral canal and distance between bilateral cornua measured in millimeters. RESULTS: The mean diameter of the sacral canal was measured to be 5.3+/-2.0 mm in our recruited patients. The mean distance between bilateral cornua was measured to be 9.7+/-1.9 mm. Caudal epidural injections failed in 7 patients. In these 7 patients, 4 had very small diameter of the sacral canal (1.6, 1.2, 1.4, and 1.5 mm). In 1 man, sonographic images revealed a closed sacral hiatus (no sacral canal diameter can be measured). Two patients revealed flow of fresh blood into the syringe while checking for the escape of cerebrospinal fluid after the needles were inserted into the sacral canal. For safety reasons, steroid injections were not performed in these 2 patients. CONCLUSIONS: Ultrasound may be used as an effective screening tool for caudal epidural injections. Anatomic variations of the sacral hiatus can be clearly observed using ultrasound. Sonographic images indicating a closed sacral canal and sacral diameters ranging from 1.2 to 1.6mm may suggest a higher failure rate in caudal epidural injection. PMID- 20298825 TI - Effectiveness of pulmonary rehabilitation in reducing health resources use in chronic obstructive pulmonary disease. AB - OBJECTIVE: To determine the effectiveness of a multidisciplinary, outpatient pulmonary rehabilitation (PR) program in patients with severe and very severe chronic obstructive pulmonary disease (COPD). PR is recommended in advanced COPD, but there is limited evidence on the effectiveness of PR in reducing health care resources when applied in outpatients. DESIGN: Before and after intervention, a prospective research trial of patients enrolled in a PR program. SETTING: Outpatient respiratory department in a specialized hospital. PARTICIPANTS: We considered prospectively 82 consecutive patients with advanced COPD and finally studied 72 patients who completed the PR intensive phase. INTERVENTION: PR program. MAIN OUTCOME MEASURES: The effectiveness of this PR program was assessed by comparing health resources use from the year before and the year after PR. Clinical variables including dyspnea; the body mass index, obstruction, dyspnea, exercise capacity (BODE) index; and the Chronic Respiratory Questionnaire and health resources use including the number of exacerbations, the number of hospitalizations, and days of hospitalization. RESULTS: Patients had a forced expiratory volume in the first second percentage predicted (mean +/- SD) of 33.0+/-9.8 and a BODE index of 5.0+/-2.0. Significant improvements after PR were found in dyspnea, exercise capacity, and quality of life and on the BODE index (P<.05). Compared with the 12 months before PR, there were also significant reductions during the year after PR on exacerbations (3.4+/-3.5 vs 1.9+/-2.0, P=.002), hospitalizations (2.4+/-2.0 vs 0.9+/-1.2, P<.001), and days of hospitalization (36.1+/-32.7 vs 16.1+/-31.3, P<.001) (ie, a reduction of 44%, 63%, and 55%, respectively; all P<.05). CONCLUSIONS: We conclude that a multidisciplinary, outpatient PR program substantially reduces health resources use in patients with severe and very severe COPD. PMID- 20298826 TI - Demographic and clinical variation in Veterans Health Administration provision of assistive technology devices to veterans poststroke. AB - OBJECTIVES: To examine variation in provision of assistive technology (AT) devices and the extent to which such variation may be explained by patient characteristics or Veterans Health Administration (VHA) administrative region. DESIGN: Retrospective population-based study. SETTING: VHA. PARTICIPANTS: Veterans poststroke in fiscal years 2001 and 2002 (N=12,046). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURE: Provision of 8 categories of AT devices. RESULTS: There was considerable regional variation in provision of AT. For example, differences across administrative regions in the VHA ranged from 5.1 to 28.1 standard manual wheelchairs per 100 veterans poststroke. Using logistic regression, with only demographic variables as predictors of standard manual wheelchair provision, the c statistic was .62, and the pseudo R(2) was 2.5%. Adding disease severity increased the c statistic to .67 and the pseudo R(2) to 6.2%, and adding Veteran Integrated Network System further increased the c statistic to .72 and pseudo R(2) to 9.8%. CONCLUSIONS: Our research showed significant variation in the provision of AT devices to veterans poststroke, and it showed that patient characteristics accounted for only 6.2% of the variation. VHA administrative region and disability severity accounted for equivalent amounts of the variation. Our findings suggest the need for improvements in the process for providing AT and/or provider education concerning device provision. PMID- 20298827 TI - Community ambulation in older adults: which internal characteristics are important? AB - OBJECTIVE: To examine the internal characteristics of older adults independent in community ambulation to gain further understanding of the skills required for its successful execution. DESIGN: Exploratory factor analysis. SETTING: General community. PARTICIPANTS: Healthy, community dwelling older adults (N=113) who were cognitively intact and walked outdoors independently. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Spatiotemporal gait parameters derived from accelerometry over 6 minutes walking outdoors and a battery of measures for motor, cognitive, executive, and behavioral characteristics. RESULTS: Mean participant age +/- SD was 75.8+/-7.3 years, with almost a third of the sample over 80 years. Four factors emerged from the Factor Analysis of 23 variables: motor control, self-efficacy, executive function, and cognitive-motor interference, which together explained 61.4% of common variance. Eight variables loaded onto motor control, accounting for 34.5% of common variance; 7 items loaded onto self-efficacy, which explained 12.4% of common variance; 5 variables loaded onto executive function, accounting for 8.4% of common variance; and 3 variables loaded onto cognitive-motor interference, explaining 6% of the variance. CONCLUSIONS: Results of this study indicate that factors beyond motor control contribute to independent community ambulation in older adults, reflecting the multidimensional, complex nature of the task. Self-efficacy was shown to be more relevant than executive function to gait performance, suggesting the need for a broader approach to assessment and intervention strategies. PMID- 20298828 TI - Recovery of muscle strength and power after limb-lengthening surgery. AB - OBJECTIVE: To report muscle strength, power, and function after limb-lengthening surgery performed by using the Ilizarov technique. DESIGN: Prospective, longitudinal observational study of a cohort of consecutive patients who underwent limb-lengthening distraction followed up for 2 years after surgery. SETTING: National Health Service hospital specializing in orthopedic surgery. PARTICIPANTS: Patients (N=16) who had undergone limb-lengthening surgery performed by using the Ilizarov method (11 men, 5 women; mean age=27 y; range, 13 56 y). INTERVENTIONS: None. MAIN OUTCOME MEASURES: Muscle strength and power were assessed by using 2 validated measures: isokinetic concentric strength of the quadriceps and hamstrings measured by using a dynamometer and leg extensor power. Measures were recorded preoperatively and at 6, 12, and 24 months after the completion of lengthening. Function was measured by 2 timed tests of functional performance: stair climbing and sit-to-stand. RESULTS: Overall results were good with high reports of function and satisfactory clinical examination. Both concentric muscle strength and leg power showed a clear pattern of decreased muscle strength at 6 months after frame removal, improving throughout the study period until it was within 3% of the preoperative value at 2 years. By 2 years, self-reported function and ability to complete timed functional tests had returned to or improved on the preoperative values. Muscle strength remained slightly below the preoperative value; this was more pronounced in the quadriceps than the hamstrings. There was no association between muscle strength and the amount of lengthening that had been undertaken. CONCLUSIONS: This study suggests that there is a small residual decrease in muscle strength and power after limb lengthening surgery but that these do not adversely impact on a patients' ability to perform everyday functional activities. PMID- 20298829 TI - Rasch analysis of the Executive Interview (The EXIT-25) and introduction of an abridged version (The Quick EXIT). AB - OBJECTIVES: To evaluate the psychometric properties of the Executive Interview (EXIT-25) and to propose modifications that will improve those properties. DESIGN: Rasch analysis of existing datasets contributed by 3 prior projects, all of which examined criterion-related validity of the EXIT-25. SETTING: A large, urban, academic free-standing rehabilitation facility. PARTICIPANTS: The sample of 147 was comprised of 109 adults diagnosed with stroke evaluated during inpatient rehabilitation and 38 adults with traumatic brain injury evaluated during inpatient (n=11) or outpatient rehabilitation (n=27). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: The EXIT-25, Repeatable Battery for the Assessment of Neuropsychological Status, and Trails A and B. RESULTS: Eleven of the 25 items correlated weakly with the total measure and misfit the rating scale model. Deleting these 11 items improved the internal consistency of the remaining 14 items and enhanced the measure's criterion-related validity. CONCLUSIONS: The EXIT-25 can be reduced from 25 to 14 items without reducing internal consistency. Convergent validity of the abbreviated measure is supported by moderate-size correlations with standard measures of cognitive deficits. PMID- 20298830 TI - Psychometric properties of the community integration questionnaire adjusted for people with aphasia. AB - OBJECTIVES: To describe the feasibility of the Community Integration Questionnaire (CIQ) adjusted for use in people with aphasia and to report its psychometric properties in people with aphasia (internal consistency, factor analysis, test-retest reliability, convergent validity). DESIGN: A cross sectional, interview-based psychometric study. Test-retest reliability was evaluated in 20 people (minimal to severe aphasia) by 2 different interviewers within a 2-week period. SETTING: Community. PARTICIPANTS: In total 490 stroke survivors with (minimal to severe) aphasia were approached, of which 165 (34%) participants returned the answering letter. Participants (N=150) agreed to take part and were interviewed using a structured interview format. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Community Integration Questionnaire (CIQ), Frenchay Aphasia Screening Test, Barthel Index, Dartmouth Coop Functional Health Assessment Charts (COOP)-World Organisation of Family Doctors (WONCA) Charts, Life Satisfaction Questionnaire. RESULTS: A total of 150 stroke survivors with aphasia completed the CIQ adjusted for people with aphasia. The CIQ adjusted for people with aphasia was a feasible instrument. Results showed good internal consistency for the CIQ total (standardized Cronbach alpha=.75), excellent test retest reliability (intraclass correlation coefficient=.96), moderate correlations with the Barthel Index, the COOP-WONCA, and the Life Satisfaction Questionnaire with regard to construct validity. Significant relations were found with regard to age and aphasia severity. CONCLUSIONS: The CIQ adjusted for people with aphasia seems to be an adequate instrument to assess participation in people with aphasia. PMID- 20298831 TI - Patient-reported cognitive and communicative functioning: 1 construct or 2? AB - OBJECTIVES: To examine the dimensionality of scales for measuring patient reported cognitive and communicative functioning in a sample of stroke survivors and to evaluate the consequences for measurement of treating them as a single, undifferentiated construct. DESIGN: Secondary analysis of existing cross sectional data. SETTING: Data were collected in outpatient rehabilitation clinics and in the community. PARTICIPANTS: Unilateral stroke survivors (N=316) 3 months or more postonset referred for participation in research. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: The Burden of Stroke Scale cognition and communication domain scales were evaluated by using confirmatory factor analysis, Rasch analysis, and tests of differential item functioning (DIF). To evaluate the impact of multidimensionality on the measurement of individual patients, separately estimated cognition and communication scores were compared. Combined and separately estimated scores were also examined for responsiveness to group differences in the presence of cognitive and communicative impairment. RESULTS: Factor analysis and Rasch model fit analyses equivocally supported the unidimensionality of the item pool. DIF analyses between participants with right versus left hemisphere stroke suggested multidimensionality. Scaling cognition and communication items separately resulted in different person scores for a significant number of patients and greater responsiveness to group differences. CONCLUSIONS: Patient-reported scales assessing communication along with more general cognitive activities may possess an internal structure that is inconsistent with a unidimensional measurement model with potential negative consequences for measurement. PMID- 20298832 TI - 5-repetition sit-to-stand test in subjects with chronic stroke: reliability and validity. AB - OBJECTIVES: To examine the (1) intrarater, interrater, and test-retest reliability of the 5-repetition sit-to-stand test (5-repetition STS test) scores, (2) correlation of 5-repetition STS test scores with lower-limb muscle strength and balance performance, and (3) cut-off scores among the 3 groups of subjects: the young, the healthy elderly, and subjects with stroke. DESIGN: Cross-sectional study. SETTING: University-based rehabilitation center. PARTICIPANTS: A convenience sample of 36 subjects: 12 subjects with chronic stroke, 12 healthy elderly subjects, and 12 young subjects. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: 5-Repetition STS test time scores; hand-held dynamometer measurements of hip flexors, and knee flexors and extensors; ankle dorsiflexors and plantarflexors muscle strength; Berg Balance Scale (BBS); and limits of stability (LOS) test using dynamic posturography. RESULTS: Excellent intrarater reliability of intraclass correlation coefficient (ICC) (range, .970-.976), interrater reliability (ICC=.999), and test-retest reliability (ICC range, .989 .999) were found. Five-repetition STS test scores were also found to be significantly associated with the muscle strength of affected and unaffected knee flexors (rho=-.753 to -.830; P<.00556) of the subjects with stroke. No significant associations were found between 5-repetition STS test and BBS and LOS tests in subjects with stroke. Cut-off scores of 12 seconds were found to be discriminatory between healthy elderly and subjects with stroke at a sensitivity of 83% and specificity of 75%. CONCLUSIONS: The 5-repetition STS test is a reliable measurement tool that correlates with knee flexors muscle strength but not balance ability in subjects with stroke. PMID- 20298833 TI - Psychometric validation of the Manual Ability Measure-36 (MAM-36) in patients with neurologic and musculoskeletal disorders. AB - OBJECTIVES: To evaluate the psychometric properties of the Manual Ability Measure 36 (MAM-36), a new hand function outcome measure, and to examine differences in manual abilities and item parameters in patients with neurologic and musculoskeletal conditions. DESIGN: Convenience sample from 2 time periods, cross sectional. SETTING: Outpatient rehabilitation units and private hand clinics. PARTICIPANTS: Patients (N=337; mean age, 50.3+/-14.9y) with a variety of neurologic and musculoskeletal (orthopedic) diagnoses. Most of these individuals were community dwelling, and all had residual functional limitations in the hand(s). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Rasch analysis was performed on MAM-36 data to evaluate both scale structure and psychometric properties, which include rating distribution, step measures, item fit, separation, and dimensionality. A t test was performed to examine the differences in manual abilities in patients with the 2 conditions. Uniform differential item functioning (DIF) between neurologic and musculoskeletal groups was examined. (DIF occurs when subgroup members within the sample with the same level of the underlying trait being measured respond differently to an individual item.) Manual ability estimates were recalibrated with step and common item anchoring; they were compared with those derived from the original analysis. RESULTS: The 36 items measured a single construct with no misfitting items. The scale was used as intended. The items can reliably separate the participants into 5 ability strata. Neurologic patients had a significantly lower mean manual ability than musculoskeletal patients. Fourteen items exhibited DIF. However, DIF had no effect on either scale quality or calibration of manual ability. We decided that a single rating scale is appropriate for both groups. CONCLUSIONS: This study showed that the MAM-36 has more than adequate psychometric properties and can be used as a generic outcome measure for patients with a wide variety of clinical diagnoses. PMID- 20298834 TI - Reliability of the Tardieu Scale for assessing spasticity in children with cerebral palsy. AB - OBJECTIVE: To measure the Tardieu Scale's reliability in children with cerebral palsy (CP) when used by raters with and without experience in using the scale, before and after training. DESIGN: Single-center, intrarater and interrater reliability study. SETTING: Institutional ambulatory care. PARTICIPANTS: Referred children with CP in the pretraining phase (n=5), during training (n=3), and in the posttraining phase (n=15). INTERVENTIONS: The Tardieu Scale involves performing passive muscle stretch at 2 velocities, slow and fast. The rater derives 2 parameters; the Spasticity Angle X is the difference between the angles of arrest at slow speed and of catch-and-release or clonus at fast speed; the Spasticity Grade Y is an ordinal variable that grades the intensity (gain) of the muscle reaction to fast stretch. In phase 1, experienced raters without formalized training in the scale graded elbow, knee, and ankle plantar flexors bilaterally, without and with a goniometer. In phase 2, after training, the experienced and nonexperienced raters graded the same muscles unilaterally. MAIN OUTCOME MEASURES: Intrarater and interrater reliability of the Tardieu Scale. RESULTS: After training, nonexperienced raters had mean +/- SD intrarater and interrater agreement rates across all joints and parameters of 80%+/-14% and 74%+/-16%, respectively. For experienced raters, intrarater and interrater agreement rates before training were 77%+/-13% and 66%+/-15%, respectively, versus 90%+/-8% and 81%+/-13%, respectively, after training (P<.001 for both). Specific angle measurements at the knee were less reliable for the angles of catch measured at fast speed. Across all joints, agreement rates were similar using visual or goniometric measurements. CONCLUSIONS: Both parameters of the Tardieu Scale have excellent intrarater and interrater reliability when assessed at the elbow and ankle joints of children with CP, with no difference noted between visual and goniometric measurements. Angle measurements were less reliable at the knee joints. Training was associated with a highly significant improvement in reliability. PMID- 20298835 TI - Interrater reliability of goal attainment scaling in rehabilitation of children with cerebral palsy. AB - OBJECTIVES: To determine the interrater reliability of Goal Attainment Scaling (GAS) in the routine practice of interdisciplinary rehabilitation of children with cerebral palsy, and to examine the difference in the interrater reliability of the scores between GAS scales constructed by the children's own therapists and the scales constructed by independent therapists. DESIGN: Individually tailored GAS scales, based on predetermined criteria, were constructed at the start of a 6 month rehabilitation period. The outcome was rated independently by 2 therapists at the end of the treatment period. Two different data sets were acquired, one consisting of scores on GAS scales constructed by the children's own therapists, the other of scores on GAS scales constructed by matched independent raters of the same profession. SETTING: A children's unit of a medium-sized rehabilitation center in The Netherlands. PARTICIPANTS: Physical therapists (n=8), occupational therapists (n=8), and speech therapists (n=4) participated in pairs. They constructed 2 sets of 64 GAS scales each, for 23 children with cerebral palsy. INTERVENTIONS: A 6-month interdisciplinary pediatric rehabilitation program. MAIN OUTCOME MEASURE: Interrater reliability was assessed using linear-weighted Cohen's kappa. RESULTS: The scales constructed by the children's therapists had an interrater reliability of .82 (95% confidence interval [CI], .73-.91). The interrater reliability for scales constructed by the independent raters was .64 (95% CI, .49-.79). The main reason for disagreement between raters was discrepancies in the professionals' interpretation of the children's capacities versus their actual performance during assessment. CONCLUSIONS: The interrater reliability of GAS used under optimal conditions was good, particularly for scales constructed by the children's own therapists. PMID- 20298836 TI - Trunk muscle activity during wheelchair ramp ascent and the influence of a geared wheel on the demands of postural control. AB - OBJECTIVES: To quantify levels of torso muscular demand during wheelchair ramp ascent and the ability of a geared wheel to influence trunk muscle activity. DESIGN: Repeated-measures design. Each participant completed manual wheelchair ramp ascents for each combination of 4 ramp grades (1:12, 1:10, 1:8, and 1:6) and 3 wheel conditions (in gear, out of gear, and a standard spoked wheel) in a block randomized order by wheel condition. SETTING: Biomechanics laboratory. PARTICIPANTS: Healthy novice wheelchair users (N=13; 6 men) from a university student population. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Peak electromyographic activity, expressed as a percentage of maximal voluntary isometric contraction (MVIC) of the abdominals, latissimus dorsi, and erector spinae during ramp ascent. Temporal location of peak electromyographic activity (EMG) within a propulsive cycle and integrated electromyographic activity for a single propulsive cycle. RESULTS: Abdominal peak activity increased 13.9% MVIC while peak posterior trunk muscle activity increased 4.9% MVIC between the shallowest and steepest ramp grades (P<.05). The geared wheel prevented increased peak activity of the rectus abdominis and external oblique (P>.05). Only peak electromyographic timing of the erector spinae was influenced during the push phase by increasing ramp slope. CONCLUSIONS: Increased trunk muscular demand as a result of increasing ramp slope is required to enhance stiffness of the spinal column and provide a stable base during manual propulsion. Manual wheelchair users with compromised activity capacity, compromised abdominal muscle strength, or both, may be able to navigate more difficult terrains while using a geared wheelchair wheel because of reduced demands from the abdominal musculature in the geared wheel condition. PMID- 20298837 TI - Generalization of prism adaptation for wheelchair driving task in patients with unilateral spatial neglect. AB - OBJECTIVES: To verify the efficacy of prism adaptation as a practical means of rehabilitation for subjects with unilateral spatial neglect by conducting goal directed tasks in the presence of similar visual flankers in the right hemispace using an activity of daily living, namely, wheelchair operation. DESIGN: Prospective cohort study. SETTING: Rehabilitation center located in Japan. PARTICIPANTS: Patients with unilateral spatial neglect (N=10). INTERVENTION: Prism adaptation. MAIN OUTCOME MEASURES: A midpoint-directed task in which the subject faces the center of 2 symbols placed in front and moves the wheelchair toward it, and a goal-directed task in which the subject must differentiate a single target from multiple symbols and move the wheelchair toward it. RESULTS: In the midpoint-directed task, there was a significant shift in the reach position bias from +27.7 cm prior to prism adaptation to +3.1cm after prism adaptation (P<.01). In the goal-directed task, the time taken to reach the outer left target decreased from 21.2 seconds prior to prism adaptation to 11.8 seconds after prism adaptation, and the difference between placement of the targets was eliminated. CONCLUSIONS: Prism adaptation exhibited the potential to generalize the effects on activities of daily living such as driving a wheelchair and to ameliorate unilateral spatial neglect even in the presence of right-hemispace flankers. Prism adaptation is an effective therapeutic modality in rehabilitation because it prevents the appearance of neglect symptoms despite situational or contextual changes. PMID- 20298838 TI - Relationship between age and spasticity in children with diplegic cerebral palsy. AB - OBJECTIVE: To examine the relationship between passive torque, reflex activity, co-contraction, and age during the assessment of spasticity of knee flexors and extensors in children with spastic diplegic cerebral palsy (CP). DESIGN: Retrospective. SETTING: Pediatric orthopedic hospital. PARTICIPANTS: Children (N=36) with spastic diplegic CP. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Spasticity of the knee flexors and knee extensors (as measured by peak passive torque, mean passive torque, reflex activity of the medial hamstrings, reflex activity of vastus lateralis, and co-contraction) was assessed during passive movements completed using an isokinetic dynamometer with concurrent electromyography. RESULTS: A significant positive relationship was found between age and mean knee flexor passive torque (P<.05), while a significant negative relationship was found between age and mean percentage of the range of motion with co-contraction (P<.05). CONCLUSIONS: Our results suggest that passive stiffness may play a larger role in spasticity than reflex activity as children with spastic diplegic CP age. Additional research is needed to determine whether subject age could influence the effectiveness of interventions, such as serial casting or botulinum toxin, for spasticity in children with spastic diplegic CP. PMID- 20298840 TI - A 1-year follow-up after shortened constraint-induced movement therapy with and without mitt poststroke. AB - OBJECTIVE: To explore the long-term benefits of shortened constraint-induced movement therapy (CIMT) in the subacute phase poststroke. DESIGN: A 1-year follow up after shortened CIMT (3h training/d for 2 wk) where the participants had been randomized to a mitt group or a nonmitt group. SETTING: A university hospital rehabilitation department. PARTICIPANTS: Poststroke patients (N=20, 15 men, 5 women; mean age 58.8 y; on average 14.8 mo poststroke) with mild to moderate impairments of hand function. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: The Sollerman hand function test, the modified Motor Assessment Scale, and the Motor Activity Log test. Assessments were made by blinded observers. RESULTS: One year after shortened CIMT, participants within both the mitt group and the nonmitt group showed statistically significant improvements in arm and hand motor performance and on self-reported motor ability compared with before and after treatment. No significant differences between the groups were found in any measure at any time. CONCLUSIONS: Shortened CIMT seems to be beneficial up to 1 year after training, but the restraint may not enhance upper motor function. To determine which components of CIMT are most effective, larger randomized studies are needed. PMID- 20298839 TI - Inoculation against falls: rapid adaptation by young and older adults to slips during daily activities. AB - OBJECTIVE: To determine whether aging diminishes one's ability to rapidly learn to resist falls on repeated-slip exposure across different activities of daily living. DESIGN: Quasi-experimental controlled trial. SETTING: Two university based research laboratories. PARTICIPANTS: Young (n=35) and older (n=38) adults underwent slips during walking. Young (n=60) and older (n=41) adults underwent slips during a sit-to-stand task. All (N=174) were healthy and community dwelling. INTERVENTION: Low-friction platforms induced unannounced blocks of 2 to 8 repeated slips interspersed with blocks of 3 to 5 nonslip trials during the designated task. MAIN OUTCOME MEASURES: The incidence of falls and balance loss. Dynamic stability (based on center of mass position and velocity) and limb support (based on hip height) 300 ms after slip onset. RESULTS: Under strictly controlled, identical low-friction conditions, all participants experienced balance loss, but older adults were over twice as likely as young to fall on the first, unannounced, novel slip in both tasks. Independent of age or task, participants adapted to avoid falls and balance loss, with most adaptation occurring in early trials. By the fifth slip, the incidence of falls and balance loss was less than 5% and 15%, respectively, regardless of age or task. Reductions in falls and balance loss for each task were accomplished through improved control of stability and limb support in both age groups. A rapidly reversible age- and task-dependent waning of motor learning occurred after a block of nonslip trials. Adaptation to walk slips reached a steady state in the second slip block regardless of age. CONCLUSIONS: The ability to rapidly acquire fall-resisting skills on repeated-slip exposure remains largely intact at older ages and across functional activities. Thus, repeated-slip exposure might be broadly effective in inoculating older adults against falls. PMID- 20298841 TI - Examining the relationship between cognition and driving performance in multiple sclerosis. AB - OBJECTIVE: To identify cognitive predictors of driving performance after multiple sclerosis (MS). DESIGN: Prospective design examining predictive value of cognitive measures on driving performance. SETTING: All data were collected in an outpatient research setting and an outpatient driver rehabilitation program. PARTICIPANTS: Participants were community-dwelling persons (N=66) with clinically defined MS (86% relapsing-remitting, 14% progressive) with a mean age of 43.47 years. All were active drivers who met vision requirements established by their respective states, and none required adaptive driving equipment. INTERVENTION: Not applicable. MAIN OUTCOME MEASURES: Participants were administered a comprehensive neuropsychologic assessment and a clinical behind-the-wheel (BTW) driving evaluation. Additional measures of driving performance included history of traffic violations and collisions (since MS onset). RESULTS: Logistic regression indicated that information processing speed (Symbol Digit Modality Test [SDMT]) was the strongest predictor of BTW performance. A logistic regression revealed that the strongest predictors of collision and violation frequency were visuospatial learning and recall (7/24 Spatial Recall Test [SPART 7/24]). CONCLUSIONS: These findings indicate that information processing and visuospatial skills are predictive of driving performance among persons with MS. These measures (SDMT and SPART 7/24) may serve as screening methods for identifying the potential impact of cognitive impairment on driving. Furthermore, the findings raise questions regarding the appropriateness of the BTW evaluation to evaluate driving difficulties accurately among individuals with MS. PMID- 20298842 TI - Longitudinal changes in the health-related quality of life during the first year after traumatic brain injury. AB - OBJECTIVE: To track the health-related quality of life (HRQL) at discharge and at 6 and 12 months after a traumatic brain injury (TBI) and examine factors associated with changes in each HRQL domain. DESIGN: Longitudinal cohort study. SETTING: Using codes of the International Classification of Diseases, eligible participants who had a newly diagnosed TBI were identified from discharge records of 4 hospitals in northern Taiwan. Information on the HRQL and injury-related characteristics at the initial and 2 follow-up assessments was collected by extracting medical records and conducting telephone interviews. PARTICIPANTS: Subjects (N=158) participated in the initial assessment, and 147 and 146, respectively, completed the follow-up assessments at 6 and 12 months after injury. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURE: The brief version of the World Health Organization Quality of Life (WHOQOL-BREF) with 4 domains of physical capacity, psychologic well being, social relationships, and environment. RESULTS: Scores on all WHOQOL-BREF domains except social relationships greatly improved over the first 6 months and showed continued improvement at 12 months after injury. The domain scores of the WHOQOL-BREF at discharge were significantly associated with the preinjury HRQL level, marital status, alcohol consumption at the time of injury, Glasgow Outcome Scale (GOS) level, cognition, activities of daily living, social support, and depressive status. However, after adjusting for these baseline differences, only the GOS level and depressive status significantly influenced longitudinal changes in the psychologic and social domains over the 12-month period. Changes in the physical and environmental domains were not significantly associated with any characteristics of the study. CONCLUSIONS: During the first year after a TBI, the magnitude of HRQL recovery differed across different HRQL domains. Many factors may have significant associations with the initial domain scores of HRQL after TBI; however, only a few factors can significantly influence longitudinal changes in the HRQL. PMID- 20298843 TI - Mental health and posttraumatic stress symptoms 2 years after severe multiple trauma: self-reported disability and psychosocial functioning. AB - OBJECTIVES: To describe mental health and posttraumatic stress symptoms (PTSS) for patients with severe multiple trauma at 2 years postinjury. Further, objectives were to examine relationships between PTSS and factors related to the person, injury, and postinjury physical and psychosocial functioning from the time of return home to 2 years after injury. The final aim was to identify predictors of PTSS and mental health at 2 years. DESIGN: Prospective cohort study with a 2-year follow-up. SETTING: Hospital and community setting. PARTICIPANTS: Patients (N=99) age 18 to 67 years with multiple trauma and a New Injury Severity Score (NISS) greater than 15 treated at a regional trauma referral center. Mean age +/- SD was 35.3+/-14.2 years; 83% were men. Mean NISS +/- SD was 34.9+/-12.7. INTERVENTION: Not applicable. MAIN OUTCOME MEASURES: Postinjury psychologic distress associated with depression on the Medical Outcomes Study 36-Item Short Form Health Survey Mental Health scale and PTSS on the Post-Traumatic Symptom Scale 10 (PTSS-10) at 2 years post injury. Self-reported physical, mental, and cognitive functioning at the return home and 1 and 2 years, and coping strategies. RESULTS: Mean PTSS-10 score +/- SD at 2 years was 25.6+/-12.2. Twenty percent had a PTSS-High score, indicating posttraumatic stress disorder (PTSD). Twenty-seven percent had Mental Health scores indicating depression. Predictors of PTSS were sex (female), younger age, avoidant coping, pain, mental health, and cognitive functioning on the return home, which explained 70% of the variance in PTSS-10 score. CONCLUSIONS: Twenty percent had a PTSS-High score indicating PTSD at 2 years postinjury. The personal factors sex (female), younger age, and avoidant coping and the functional factors pain, mental health, and cognitive functioning predicted PTSS at 2 years. PMID- 20298844 TI - Aging with traumatic brain injury: cross-sectional follow-up of people receiving inpatient rehabilitation over more than 3 decades. AB - OBJECTIVE: To investigate aging with traumatic brain injury (TBI) by determining if long-term outcomes after TBI are predicted by years postinjury and age at injury after controlling for the severity of the injury and sex. DESIGN: Cross sectional follow-up telephone survey. SETTING: Community residents who had received initial treatment in a comprehensive inpatient rehabilitation hospital. PARTICIPANTS: Survivors of TBI (N=243) stratified by years postinjury (in seven 5 year cohorts ranging from 1 to over 30 years postinjury) and by age at injury (in 2 cohorts of people injured before or after age 30). INTERVENTIONS: None. MAIN OUTCOME MEASURES: Measures of postconcussive symptoms, major secondary conditions including fatigue (Modified Fatigue Impact Scale), physical and cognitive activity limitations (FIM, Alertness Behavior Subscale of the Sickness Impact Profile, Medical Outcomes Study 12-Item Health Status Survey Short Form), societal participation restrictions (Craig Handicap Assessment and Reporting Technique), environmental barriers (Craig Hospital Inventory of Environmental Factors), and perceived quality of life (Satisfaction with Life Scale). RESULTS: Most problems identified by the outcome measures were reported by one fourth to one half of the study participants. Increasing decades postinjury predicted declines in physical and cognitive functioning, declines in societal participation, and increases in contractures. Increasing age at injury predicted declines in functional independence, increases in fatigue, declines in societal participation, and declines in perceived environmental barriers. CONCLUSIONS: This investigation has increased our understanding of the aging process after TBI by demonstrating that both components of aging (years postinjury and age at injury) are predictive of several outcomes after TBI. PMID- 20298845 TI - Neuropsychologic assessment and cognitive rehabilitation in a patient with locked in syndrome and left neglect. AB - We describe a patient affected by severe incomplete locked-in syndrome (LIS) and left neglect caused by a combination of vascular lesions. Our patient's neglect prevented the use of augmentative communication devices based on a computerized eye-tracker system. For this reason, we adapted a visual scanning training for neglect rehabilitation. At the end of the rehabilitative training, the patient had regained full exploration of the monitor and could use the eye-tracker system for communicative purposes. This case report shows that specific rehabilitative approaches can be devised in severely disabled LIS patients with additional brain lesions and specific cognitive defects. PMID- 20298848 TI - Distribution coefficients of 60 elements on TODGA resin: application to Ca, Lu, Hf, U and Th isotope geochemistry. AB - Batch equilibration experiments are conducted to measure the distribution coefficients (K(d)) of a large number of elements in nitric, nitric plus hydrofluoric, and hydrochloric acids on Eichrom TODGA extraction chromatography resin. The K(d)s are used to devise a multi-element extraction scheme for high precision elemental and isotopic analyses of Ca, Hf, Lu, Th and U in geological materials, using high-purity lithium metaborate (LiBO(2)) flux fusion that allows rapid digestion of even the most refractory materials. The fusion melt, dissolved in nitric acid, is directly loaded to a TODGA cartridge on a vacuum chamber for elemental separation. An Ln-Spec cartridge is used in tandem with TODGA for Lu purification. The entire procedure, from flux digestion to preparation for isotopic analysis, can be completed in a day. The accuracy of the proposed technique is tested by measuring the concentrations of Ca (standard bracketing), Hf, Lu, Th and U (isotope dilution), and the isotopic composition of Hf in geostandards (USNM3529, BCR-2, BHVO-1, AGV-1 and AGV-2). All measurements are in excellent agreement with recommended literature values, demonstrating the effectiveness of the proposed analytical procedure and the versatility of TODGA resin. PMID- 20298849 TI - A graphene-based electrochemical sensor for sensitive detection of paracetamol. AB - An electrochemical sensor based on the electrocatalytic activity of functionalized graphene for sensitive detection of paracetamol is presented. The electrochemical behaviors of paracetamol on graphene-modified glassy carbon electrodes (GCEs) were investigated by cyclic voltammetry and square-wave voltammetry. The results showed that the graphene-modified electrode exhibited excellent electrocatalytic activity to paracetamol. A quasi-reversible redox process of paracetamol at the modified electrode was obtained, and the over potential of paracetamol decreased significantly compared with that at the bare GCE. Such electrocatalytic behavior of graphene is attributed to its unique physical and chemical properties, e.g., subtle electronic characteristics, attractive pi-pi interaction, and strong adsorptive capability. This electrochemical sensor shows an excellent performance for detecting paracetamol with a detection limit of 3.2x10(-8)M, a reproducibility of 5.2% relative standard deviation, and a satisfied recovery from 96.4% to 103.3%. The sensor shows great promise for simple, sensitive, and quantitative detection and screening of paracetamol. PMID- 20298850 TI - Protein determination using methylene blue in a synchronous fluorescence technique. AB - A new method for detecting protein by synchronous fluorescence enhancement was developed, based on the combination of near infrared (NIR) fluorescence and the dedimerization phenomenon of methylene blue (MB). Under analytical conditions, there are linear relationships between the enhancing extent of synchronous fluorescence of MB-sodium dodecyl benzene sulfonate (SDBS)-protein at 667nm and the concentration of protein in the range of 8.0x10(-8)-4.0x10(-5)gmL(-1) for bovine serum albumin (BSA), 1.0x10(-7)-3.5x10(-5)gmL(-1) for egg albumin (EA). The detection limits (S/N=3) of BSA and EA are 8.9ngmL(-1) and 10.0ngmL(-1), respectively. The fluorescence enhancement mechanism is discussed in detail. Results from multiple techniques indicate that the fluorescence enhancement of the system originates from the hydrophobic microenvironment provided by BSA and SDBS, and the formation of an MB-SDBS-BSA complex, as well as the deaggregation of some MB dimer. PMID- 20298851 TI - Effect of traditional Chinese medicine berberine on type 2 diabetes based on comprehensive metabonomics. AB - A comprehensive metabonomic method, in combination with fingerprint analysis and target analysis, was performed to reveal potential mechanisms of berberine action in the treatment of patients with type 2 diabetes and dyslipidemia. Serum samples of 60 patients before and after treatment with either berberine or placebo were collected. Ultra-performance liquid chromatography and quadrupole time-of-flight tandem mass spectrometry (UPLC Q-TOF MS) coupled with pattern recognition analysis were used to identify changes in global serum metabolites. Compared with placebo, patients before and after berberine treatment could be separated into distinct clusters as displayed by the orthogonal signal correction filtered partial least-squares discriminant analysis (OSC-PLS-DA) score plot, which indicated changes in circulating metabolites after berberine treatment. Among them, free fatty acids changed markedly. These were further quantified by UPLC combined with single quadrupole mass spectrometry (UPLC SQ MS). There was a highly significant decrease in the concentrations of 13 fatty acids following berberine administration. 10 fatty acids also differed statistically from placebo. These results suggest that berberine might play a pivotal role in the treatment of type 2 diabetes through down-regulating the high level of free fatty acids and that comprehensive metabonomic measurements are potentially very useful for studying the mechanisms of action of traditional Chinese medicines. PMID- 20298852 TI - Silica gel-polyethylene glycol as a new adsorbent for solid phase extraction of cobalt and nickel and determination by flame atomic absorption spectrometry. AB - In this paper a novel solid phase extraction method to determine Co(II) and Ni(II) using silica gel-polyethylene glycol (Silica-PEG) as a new adsorbent is described. The method is based on the adsorption of cobalt and nickel ions in alkaline media on polyethylene glycol-silica gel in a mini-column, elution with nitric acid and determination by flame atomic absorption spectrometry. The adsorption conditions such as NaOH concentration, sample volume and amount of adsorbent were optimized in order to achieve highest sensitivity. The calibration graph was linear in the range of 0.5-200.0ngmL(-1) for Co(II) and 2.0-100.0ngmL( 1) for Ni(II) in the initial solution. The limit of detection based on 3S(b) was 0.37ngmL(-1) for Co(II) and 0.71ngmL(-1) for Ni(II). The relative standard deviations (R.S.D.) for ten replicate measurements of 40ngmL(-1) of Co(II), and Ni(II) were 3.24 and 3.13%, respectively. The method was applied to determine Co(II) and Ni(II) in black tea, rice flour, sesame seeds, tap water and river water samples. PMID- 20298853 TI - Combination of ionic liquid-based dispersive liquid-liquid micro-extraction with stopped-flow spectrofluorometry for the pre-concentration and determination of aluminum in natural waters, fruit juice and food samples. AB - In this research, we combined ionic liquid-based dispersive liquid-liquid micro extraction (IL-based DLLME) with stopped-flow spectrofluorometry (SFS) to evaluate the concentration of aluminum in different real samples at trace level. 1-Hexylpyridinium hexafluorophosphate [Hpy][PF(6)] ionic liquid and 8 hydroxyquinoline (oxine), which forms a highly fluorescent complex with Al(3+), were chosen as the extraction solvent and chelating agent, respectively. The hydrophobic Al-oxine complex was extracted into the [Hpy][PF(6)] and separated from the aqueous phase. Then, the concentration of the enriched aluminum in the sediment phase was determined by SFS. Some effective parameters that influence the SFS signals and the micro-extraction efficiency, such as the suction and sending time, the concentration of the chelating agent, pH, the amount of the ionic liquid, the type of disperser solvent and diluting agent, ionic strength, extraction time, equilibration temperature and centrifugation time were investigated and optimized. In the optimum experimental conditions, the limit of detection (3s) and enrichment factor were 0.05microgL(-1) and 100, respectively. The relative standard deviation (RSD) for six replicate determinations of 6microgL(-1) Al was 1.7%. The calibration graph using the pre-concentration system was linear in the range of 0.06-15microgL(-1) with a correlation coefficient of 0.9989. The developed method was validated by the analysis of certified reference materials and applied successfully to the determination of aluminum in several water, fruit juice and food samples. PMID- 20298854 TI - Flow-injection catalytic spectrophotometic determination of molybdenum(VI) in plants using bromate oxidative coupling of p-hydrazinobensenesulfonic acid with N (1-naphthyl)ethylenediamine. AB - A novel flow-injection spectrophotometry has been developed for the determination of molybdenum(VI) at nanograms per milliliter levels. The method is based on the catalytic effect of molybdenum(VI) on the bromate oxidative coupling of p hydrazinobenzenesulfonic acid with N-(1-naphthyl)ethylenediamine to form an azo dye (lambda(max)=530nm). Chromotropic acid (4,5-dihydroxy-2,7 naphthalenedisulfonic acid) acted as an effective activator for the molybdenum(VI)-catalyzed reaction and increased the sensitivity of the method. The reaction was monitored by measuring the change in absorbance of the dye produced. The proposed method allowed the determination of molybdenum(VI) in the range 1.0-20ngmL(-1) with sample throughput of 15h(-1). The limit of detection was 0.5ngmL(-1) and a relative standard deviation for 10ngmL(-1) molybdenum(VI) (n=10) was 2.5%. The interfering ions were eliminated by using the combination of a masking agent and on-line minicolumn packed with cation exchanger. The present method was successfully applied to the determination of molybdenum(VI) in plant foodstuffs. PMID- 20298855 TI - Rapid detection of aflatoxin B(1) on membrane by dot-immunogold filtration assay. AB - Immunofiltration assay for mycotoxins in which nitrocellulose membrane (NCM) was used as a support and enzyme was used as the label has been developed since the late 1980s. As colloidal gold is a good labeling substance that can accelerate antibody-antigen reaction which result can be read directly by naked eyes, the colloidal gold particles could replace the enzyme to be labeled to antibody in aflatoxin B(1) (AFB(1)) immunoassay. Dot-immunogold filtration assay (DIGFA) of AFB(1) on NCM was developed in this study. At first, the colloidal gold was synthesized and colloidal gold-monoclonal antibody (McAb) conjugates against AFB(1) were prepared at pH 7.0 of colloidal gold solution, 0.018mg/mL of McAb. Then the colloidal gold-McAb conjugates were used to develop AFB(1) DIGFA, which detection time was only 15min, six times less than that of ELISA. With this method to determine the standard AFB(1) solution, the results demonstrated a visual detection limit of approximately 2ng/mL of AFB(1), which was similar to that of ELISA. This method had good specificities for AFG(1), AFG(2) and AFM(1) and a little cross-reactivity with AFB(2). 45 food samples collected from the markets were subjected to DIGFA and the results showed that one corn sample was positive and in agreement that of HPLC. It is suggested that DIGFA developed in current study has a potential use as a rapid and cost-effective screening tool for the determination of AFB(1) in foods in the field within 15min without complicated steps. PMID- 20298856 TI - Combining the least correlation design, wavelet packet transform and correlation coefficient test to reduce the size of calibration set for NIR quantitative analysis in multi-component systems. AB - The paper focuses on solving a common and important problem of NIR quantitative analysis in multi-component systems: how to significantly reduce the size of the calibration set while not impairing the predictive precision. To cope with the problem orthogonal discrete wavelet packet transform (WPT), the least correlation design and correlation coefficient test (r-test) have been combined together. As three examples, a two-component carbon tetrachloride system with 21 calibration samples, a two-component aqueous system with 21 calibration samples, and a two component aqueous system with 41 calibration samples have been treated with the proposed strategy, respectively. In comparison with some previous methods based on much more calibration samples, the results out of the strategy showed that the predictive ability was not obviously decreased for the first system while being clearly strengthened for the second one, and the predictive precision out of the third one was even satisfactory enough for most cases of quantitative analysis. In addition, all important factors and parameters related to our strategy are discussed in detail. PMID- 20298857 TI - Quantitative analysis of levodopa, carbidopa and methyldopa in human plasma samples using HPLC-DAD combined with second-order calibration based on alternating trilinear decomposition algorithm. AB - An HPLC method combined with second-order calibration based on alternating trilinear decomposition (ATLD) algorithm has been developed for the quantitative analysis of levodopa (LVD), carbidopa (CBD) and methyldopa (MTD) in human plasma samples. Prior to the analysis of the analytes by ATLD algorithm, three time regions of chromatograms were selected purposely for each analyte to avoid serious collinearity. Although the spectra of these analytes were similar and interferents coeluted with the analytes studied in biological samples, good recoveries of the analytes could be obtained with HPLC-DAD coupled with second order calibration based on ATLD algorithm, additional benefits are decreasing times of analysis and less solvent consumption. The average recoveries achieved from ATLD with the factor number of 3 (N=3) were 100.1+/-2.1, 96.8+/-1.7 and 104.2+/-2.6% for LVD, CBD and MTD, respectively. In addition, elliptical joint confidence region (EJCR) tests as well as figures of merit (FOM) were employed to evaluate the accuracy of the method. PMID- 20298858 TI - Fabrication of Pt/polypyrrole hybrid hollow microspheres and their application in electrochemical biosensing towards hydrogen peroxide. AB - Pt/polypyrrole (PPy) hybrid hollow microspheres were successfully prepared by wet chemical method via Fe(3)O(4) template and evaluated as electrocatalysts for the reduction of hydrogen peroxide. The as-synthesized products were characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), X-ray photoelectron spectra (XPS), X-ray diffraction (XRD), inductive coupled plasma emission spectrum (ICP) and Fourier-transform infrared spectra (FTIR) measurements. The results exhibited that ultra-high-density Pt nanoparticles (NPs) were well deposited on the PPy shell with the mean diameters of around 4.1nm. Cyclic voltammetry (CV) results demonstrated that Pt/PPy hybrid hollow microspheres, as enzyme-less catalysts, exhibited good electrocatalytic activity towards the reduction of hydrogen peroxide in 0.1M phosphate buffer solution (pH=7.0). The composite had a fast response of less than 2s with linear range of 1.0-8.0mM and a relatively low detection limit of 1.2microM (S/N=3). The sensitivity of the sensor for H(2)O(2) was 80.4mAM(-1)cm(-2). PMID- 20298859 TI - Pseudo-homogeneous immunoextraction of epitestosterone from human urine samples based on gold-coated magnetic nanoparticles. AB - A pseudo-homogeneous immunoextraction method based on gold-coated magnetic nanoparticles (MNPs) for the specific extraction and quantitative analysis of epitestosterone (17alpha-hydroxy-4-androsten-3-one, abbreviated as "ET") from human urine samples by high-performance liquid chromatography (HPLC) has been developed. Half-IgG of anti-ET monoclonal antibodies were covalently immobilized onto (Fe(3)O(4))(core)-Au(shell) (Fe(3)O(4)@Au) MNPs. An external magnetic field was applied to collect the MNPs which were then rinsed with distilled water followed by elution with absolute methanol to obtain ET as the analyte. The obtained extraction solution was analyzed by HPLC with UV detection (244nm) within 12min. The standard calibration curve for ET showed good linearity in the range of 20-200ngmL(-1) in phosphate-buffered saline (PBS) solutions with acceptable accuracy and precision. Limit of detection for ET was 0.06ngmL(-1) due to an enrichment factor of 100-fold was achieved. The results obtained by the present method for spiked human urine samples were in agreement with those from indirect competitive enzyme-linked immunoadsorbent assays (ELISAs). The antibody conjugated Fe(3)O(4)@Au MNPs are novel materials for immunoaffinity extraction. Compared with the conventional technique using immunoaffinity column, the method described here for sample pretreatment was fast, highly specific, and easy to operate. PMID- 20298860 TI - Pore expansion of highly monodisperse phenylene-bridged organosilica spheres for chromatographic application. AB - Monodisperse phenylene-bridged organosilica spheres show great potential as chromatographic stationary phase. In this paper, the tunable particle size of monodisperse phenylene-bridged organosilica spheres were prepared by co condensing different proportion of 1,4-bis(triethoxysilyl)benzene (1,4-BTEB) and tetraethylorthosilicate (TEOS), and then pore size was expanded by two-step post synthesis hydrothermal treatments using N,N-dimethyldecylamine (DMDA)/dodecylamine (DDA) and tris-(hydroxymethyl)-aminomethane (TRIS) in turn. Phenylene-bridged organosilica spheres with particle size of 3.0-3.5microm and pore size of 85A were further surface modified by C(18) group and tested in reversed-phase high performance liquid chromatography (RP-HPLC). The primary chromatographic results demonstrated that C(18) bonded phenylene-bridged organosilica stationary phase has high retention and good chemical stability in the high pH mobile phase, which indicated that the phenylene-bridged organosilica can be used for HPLC packing supports. PMID- 20298861 TI - Extraction of trace amounts of mercury with sodium dodecyle sulphate-coated magnetite nanoparticles and its determination by flow injection inductively coupled plasma-optical emission spectrometry. AB - A new method for solid-phase extraction and preconcentration of trace amounts Hg(II) from environmental samples was developed by using sodium dodecyle sulphate coated magnetite nanoparticles (SDS-coated Fe(3)O(4) NPs) as a new extractant. The procedure is based on the adsorption of the analyte, as mercury-Michler's thioketone [Hg(2)(TMK)(4)](2+) complex on the negatively charged surface of the SDS-coated Fe(3)O(4) NPs and then elution of the preconcentrated mercury from the surface of the SDS-coated Fe(3)O(4) NPs prior to its determination by flow injection inductively coupled plasma-optical emission spectrometry. The effects of pH, TMK concentration, SDS and Fe(3)O(4) NPs amounts, eluent type, sample volume and interfering ions on the recovery of the analyte were investigated. Under optimized conditions, the calibration curve was linear in the range of 0.2 100ngmL(-1) with r(2)=0.9994 (n=8). The limit of detection for Hg(II) determination was 0.04ngmL(-1). Also, relative standard deviation (R.S.D.) for the determination of 2 and 50ngmL(-1) of Hg(II) was 5.2 and 4.7% (n=6), respectively. Due to the quantitative extraction of Hg(II) from 1000mL of the sample solution an enhancement factor as large as 1230-fold can be obtained. The proposed method has been validated using a certified reference materials, and also the method has been applied successfully for the determination of Hg(II) in aqueous samples. PMID- 20298862 TI - High performance liquid chromatography with two simultaneous on-line antioxidant assays: Evaluation and comparison of espresso coffees. AB - The antioxidant profiles of various espresso coffees were established using HPLC with UV-absorbance detection and two rapid, simultaneous, on-line chemical assays that enabled the relative reactivity of sample components to be screened. The assays were based on (i) the colour change associated with reduction of the 2,2' diphenyl-1-picrylhydrazyl radical (DPPH*); and (ii) the emission of light (chemiluminescence) upon reaction with acidic potassium permanganate. Results from the two approaches were similar and reflected the complex array of antioxidant species present in the samples. However, some differences in selectivity were observed. Chromatograms generated with the chemiluminescence assay contained more peaks, which was ascribed to the greater sensitivity of the reagent towards minor, readily oxidisable sample components. The three coffee samples produced closely related profiles, signifying their fundamentally similar chemical compositions and origin. Nevertheless, the overall intensity and complexity of the samples in both UV absorption and antioxidant assay chromatograms were aligned with the manufacturers description of flavour intensity and character. PMID- 20298863 TI - Rapid pretreatment-free immunochromatographic assay of chloramphenicol in milk. AB - A pretreatment-free immunochromatographic assay for detection of chloramphenicol (CAP) in milk was developed. The assay is based on competition between CAP molecules in the sample and immobilized CAP-protein conjugate for binding to monoclonal anti-CAP antibodies conjugated with colloidal gold particles (average diameter 30nm). The assay is carried out in the course of sample flowing along test strip with immobilized reactants, and its results can be detected by the naked eye or by a photometric device. Effect of the concentration of immunoreactants on assay characteristics was studied. The assay protocol with maximal sensitivity and reliability was optimized using measured values of brightness of lines. Detection limit for CAP is 10ngmL(-1). Assay duration is 10min, and it can be carried out at room temperature without any additional devices and reactants. The developed test strip has been applied to CAP detection in dairy products. PMID- 20298864 TI - A simple automated system for measuring soil respiration by gas chromatography. AB - An automated dynamic closed chamber system for CO(2) sampling and analysis was developed for the measurement of soil respiration under laboratory conditions. The system is composed by a gas chromatograph linked to a fully computerised sampling system composed by 16 sample jars and 2 multiposition valves. Besides CO(2), the system can automatically and simultaneously measure CH(4), N(2)O and other gases of environmental interest. The detection limits of the system for CO(2), N(2)O and CH(4) were 2, 1 and 4ppmv, respectively. The accuracy of the system, expressed as percent bias, was -0.88, -0.94 and -3.17% for CO(2), N(2)O and CH(4), respectively, with relative standard deviation of 0.42, 0.68 and 0.61%. Measurement of CO(2) evolved following acidification of a known amount of reagent grade CaCO(3) showed a standard recovery of 96.8+/-2.5% reached within 30s after acidification. A linear response of CO(2) respiration was obtained for a wide range of operative conditions (5-60min accumulation time, 10-80g soil sample size, 10-60mLmin(-1) air flow rate, 15-25 degrees C temperature of incubation) demonstrating the flexibility of the system, which allows for the measurement of soil samples characterised by different rates of gas evolution. Moreover, the results obtained with soil samples showed that within the above conditions the proposed system is not affected by potential limitations of static closed chamber systems such as CO(2) dissolution in the soil solution, reduced rate of CO(2) diffusion from soil to headspace and CO(2) inhibition of microbial activity. The system was also capable to detect significant changes in N(2)O emissions from soil amended with different amounts of glutamic acid. The automatic and frequent measurements provided by the system make possible an accurate description of the dynamics of gas evolution from soil samples under laboratory conditions. PMID- 20298865 TI - Preparation of phenylboronic acid functionalized cation-exchange monolithic columns for protein separation and refolding. AB - In this study, we described a simple and effective modification procedure to prepare poly (methacrylate-co-ethylene glycol dimethacrylate) monolithic columns functionalized with 3-aminophenylboronic acid. The column morphology, pore size and specific surface area of the fabricated monolith were characterized by scanning electron microscopy, X-ray photoelectron spectroscopy, thermogravimetric analysis, and mercury intrusion porosimeter, respectively. The frontal analysis was carried out for dynamic loading capacity of the model protein on the modified column. The chromatographic performance of the cation-exchange monolith was evaluated through separating a mixture of five proteins such as lysozyme, cytochrome c, ribonuclease A, trypsin and bovine serum albumin and one-step purification of lysozyme from egg whites, and the expected results were obtained. In addition, the functionalized column was used to refold ribonuclease A and cytochrome c, and this procedure was monitored by circular dichroism and fluorescence spectroscopy. Compared with the conventional dilution refolding method, the ion-exchange chromatography refolding method developed here is more effective for specific bioactivity recovery. PMID- 20298866 TI - Enantioanalysis of R-deprenyl based on its molecular interaction with C(70) fullerenes. AB - Two enantioselective, potentiometric membrane electrodes based on [5,6]fullerene C(70) (1) and diethyl (1,2-methanofullerene C(70))-71-71-dicarboxylate (2) immobilized in carbon paste, were designed for the enantioanalysis of R-deprenyl. The electrodes exhibited near-Nernstian slopes: 57.90 (1) and 59.00mV/decade of concentration (2), respectively with low limits of detection 5.9x10(-11) (1) and 9.6x10(-11)mol/L (2), respectively. The linear concentration ranges are between 10(-10) and 10(-4)mol/L (1) and between 10(-9) and 10(-4)mol/L (2), respectively. The different characteristics involved in the molecular interaction between R deprenyl and C(70) fullerenes were explained, namely (i) the stability of each molecule and (ii) the explanation of the molecular mechanism of interaction, using restricted Hartree-Fock theory, 3-21G(*) RHF-basis set. Furthermore, two intermolecular forces of interactions confer the stability of the electrodes; electrostatic interaction and moderate hydrogen bond interaction. Stability and feasibility of all the generated structures involved in this analysis were supported by their respective fundamental frequencies and energy minima. R deprenyl can be recovered with average recoveries higher than 99.10% (RSD<0.03%) from synthetic mixtures between R- and S-deprenyl. The high selectivity and enantioselectivity made possible the enantioanalysis of R-deprenyl in its pharmaceutical formulations. PMID- 20298867 TI - Simultaneous determination of 11 antibiotics and their main metabolites from four different groups by reversed-phase high-performance liquid chromatography-diode array-fluorescence (HPLC-DAD-FLD) in human urine samples. AB - A new, accurate and sensitive reversed-phase high-performance liquid chromatography (RP-HPLC) as analytical method for the quantitative determination of 11 antibiotics (drugs) and the main metabolites of five of them present in human urine has been worked out, optimized and validated. The analytes belong to four different groups of antibiotics (sulfonamides, tetracyclines, penicillins and anphenicols). The analyzed compounds were sulfadiazine (SDI) and its N(4) acetylsulfadiazine (NDI) metabolite, sulfamethazine (SMZ) and its N(4) acetylsulfamethazine (NMZ), sulfamerazine (SMR) and its N(4)-acetylsulfamerazine (NMR), sulfamethoxazole (SMX), trimetroprim (TMP), amoxicillin (AMX) and its main metabolite amoxicilloic acid (AMA), ampicillin (AMP) and its main metabolite ampicilloic acid (APA), chloramphenicol (CLF), thiamphenicol (TIF), oxytetracycline (OXT) and chlortetracycline (CLT). For HPLC analysis, diode array (DAD) and fluorescence (FLD) detectors were used. The separation of the analyzed compounds was conducted by means of a Phenomenex Gemini C(18) (150mm x 4.6mm I.D., particle size 5microm) analytical column with LiChroCART LiChrospher C(18) (4mm x 4mm, particle size 5microm) guard column. Analyzed drugs were determined within 34min using formic acid 0.1% in water and acetonitrile in gradient elution mode as mobile phase. A linear response was observed for all compounds in the range of concentration studied. Two procedures were optimized for sample preparation: a direct treatment with methanol and acetonitrile and a solid phase extraction procedure using Bond Elut Plexa columns. The method was applied to the determination of the analytes in human urine from volunteers under treatment with different pharmaceutical formulations. This method can be successfully applied to routine determination of all these drugs in human urine samples. PMID- 20298868 TI - Development of a fast and efficient ultrasonic-based strategy for DNA fragmentation. AB - Several ultrasound-based platforms for DNA sample preparation were evaluated in terms of effective fragmentation of DNA (plasmid and genomic DNA)-ultrasonic probe, sonoreactor, ultrasonic bath and the newest Vialtweeter device. The sonoreactor showed the best efficiency of DNA fragmentation while simultaneously assuring no cross-contamination of samples, and was considered the best ultrasonic tool to achieve effective fragmentation of DNA at high-throughput and avoid sample overheating. Several operation variables were studied ultrasonication time and amplitude, DNA concentration, sample volume and sample pre-treatment-that allowed optimisation of a sonoreactor-based strategy for effective DNA fragmentation. Optimal operating conditions to achieve DNA fragmentation were set to 100% ultrasonic amplitude, 100microL sample volume, 8min ultrasonic treatment (2min/sample) for a DNA concentration of 100microgmL( 1). The proposed ultrasonication strategy can be easily implemented in any laboratory setup, providing fast, simple and reliable means for effective DNA sample preparation when fragmentation is critical for downstream molecular detection and diagnostics protocols. PMID- 20298869 TI - Multiresidue determination of organochlorines in fish oil by GC-MS: a new strategy in the sample preparation. AB - A rapid, economic and environmentally friendly analytical methodology has been implemented for the determination of alpha-, beta-, gamma- and delta-HCH, p,p' DDT, p,p'-DDD and p,p'-DDE, PCBs congeners #28, #52, #101, #153, #138 and #180 and Hexachlorobenzene in fish oil. 1,2,3,4-Tetrachloronaphtalene was used as internal standard. The sample preparation, consisting of a single step of clean up and fractionation, took place in a column filled with different layers of neutral and sulphuric acid modified silica. The analytes were eluted by vacuum with of hexane. Significant reduction in terms of solvents, sorbents, and analysis time was achieved in comparison with literature. Gas chromatography coupled to mass spectrometry was used for the separation and determination of the analytes. The instrumental limits of detection were from 0.1 to 1.3ngmL(-1) and the response of the detector was linear up to 200ngmL(-1). The separation proved to be precise (RSD<3.7% in peak area) and robust in terms of peak area, peak efficacy and resolution. The methodology was validated with two certified reference materials of cod liver oil, BCR 598 and BCR 349, obtaining no statistically significant differences between the concentrations found and certified. For the analytes that were not certified, aliquots of the reference materials were spiked and the recoveries obtained were satisfactory. These results were consistent with those found previously for DDTs by gas chromatography with an electron-capture detector. The methodology was applied to the analysis of three fish oil pills sold in Spain as a dietary supplement of vitamins and omega-3 fatty acids. The sum of the analytes studied was from 64 to 80ngg(-1). The most abundant compounds are PCBs, followed by DDTs in all samples. PMID- 20298870 TI - Development of an analytical methodology to quantify melamine in milk using micellar liquid chromatography and validation according to EU Regulation 2002/654/EC. AB - Melamine is a toxic triazine, illegally used as an additive in milk to apparently increase the amount of protein. A chromatographic procedure using a C18 column and a micellar mobile phase of sodium dodecyl sulphate (0.05M) and propanol (7.5%), buffered at pH 3, and a detection set by absorbance at 210nm, was reported for the resolution and quantification of melamine in liquid and powdered milk samples. In this work, samples were diluted with a SDS solution and were directly injected, thus avoiding long extraction and experimental procedures. Melamine was eluted in nearly 9.3min without overlapping the protein band or other endogeneous compounds. The optimal mobile phase composition was taken using a chemometrical approach that considers the retention factor, efficiency and peak shape. Validation was performed following the European Commission's indications (European Decision 2002/657/EC), and the main analytical parameters studied were: linearity (0.02-100ppm; r(2)=0.999), limit of detection (5ppb), intra- and inter day precision (R.S.D. <7.6% and <9.7%, respectively) and robustness (R.S.D. <7.4% for retention time and <5.0% for area). Sensitivity was adequate to detect melamine under the safety limits proposed by the US FDA. Finally, recoveries for several milk samples were found in the 85-109% range. PMID- 20298871 TI - Ultrasensitive fluorometric determination of hydrogen peroxide and glucose by using multiferroic BiFeO(3) nanoparticles as a catalyst. AB - BiFeO(3) magnetic nanoparticles (BFO MNPs) are used as a catalyst to develop an ultrasensitive method for the determination of H(2)O(2). It is found that BFO MNPs can catalyze the decomposition of H(2)O(2) to produce OH radicals, which in turn oxidize the weakly fluorescent benzoic acid to a strongly fluorescent hydroxylated product with a maximum emission at 405nm. This makes it possible to sensitively quantify traces of H(2)O(2). Under optimized conditions, the fluorescence intensity is observed to be well linearly correlated with H(2)O(2) concentration from 2.0x10(-8) to 2.0x10(-5)molL(-1) with a detection limit of 4.5x10(-9)molL(-1) (S/N=3). In addition, a selective method for glucose determination is developed by using both glucose oxidase and BFO MNPs, which has a linear range for glucose concentration from 1.0x10(-6) to 1.0x10(-4)molL(-1) with a detection limit of 5.0x10(-7)molL(-1). These new methods have been successfully applied for the determination of H(2)O(2) in rainwater and glucose in human serum samples. PMID- 20298872 TI - Conductive bio-Polymer nano-Composites (CPC): chitosan-carbon nanotube transducers assembled via spray layer-by-layer for volatile organic compound sensing. AB - The chemo-electrical properties of chitosan-carbon nanotubes (Chit-CNT) Conductive bio-Polymer nano-Composites (CPC) transducers processed by spray layer by-layer (LbL) technique have been investigated. Results show that unlike most synthetic polymer matrices, chitosan provides the transducer with high sensitivity towards not only polar vapours like water and methanol but also to a lesser extent toluene. Quantitative responses are obtained, well fitted with the Langmuir-Henry-Clustering (LHC) model allowing to link electrical signal to vapour content. Chit-CNT transducers selectivity was also correlated with an exponential law to the inverse of Flory-Huggins interaction parameter chi(12). These properties make Chit-CNT a good transducer to be implemented in an e-nose. Additionally, the observation by atomic force microscopy (AFM) of Chit-CNT morphology suggests a chemical nano-switching mechanism promoting tunnelling conduction and originating macroscopic vapour sensing. PMID- 20298873 TI - Comparative study of the adsorption performance of a multi-sorbent bed (Carbotrap, Carbopack X, Carboxen 569) and a Tenax TA adsorbent tube for the analysis of volatile organic compounds (VOCs). AB - A comparison between two types of adsorbent tubes, the commonly used Tenax TA and a multi-sorbent bed (Carbotrap, Carbopack X, Carboxen 569) tube developed in our laboratory, has been done to evaluate their usefulness in the analysis of VOCs in ambient air. Duplicate indoor and outdoor samples of Tenax TA and multi-sorbent tubes of 10, 20, 40, 60 and 90l were taken in Barcelona city (Spain) on July and October of 2009. Breakthrough values (defined as %VOCs found in the back tube) were determined for all sampling volumes connecting two sampling tubes in series. The analysis was performed by automatic thermal desorption (ATD) coupled with capillary gas chromatography (GC)/mass spectrometry detector (MSD). Significant differences between the concentrations obtained-from multi-sorbent bed and Tenax TA tubes are observed for the very volatile compounds (56 degrees C10% of patients undergoing percutaneous coronary intervention in routine clinical practice and is associated with impaired angiographic and long-term clinical outcome, including death or myocardial infarction. (Sirolimus-Eluting Versus Paclitaxel-Eluting Stents for Coronary Revascularization; NCT00297661). PMID- 20298924 TI - B-type natriuretic peptide and the effect of ranolazine in patients with non-ST segment elevation acute coronary syndromes: observations from the MERLIN-TIMI 36 (Metabolic Efficiency With Ranolazine for Less Ischemia in Non-ST Elevation Acute Coronary-Thrombolysis In Myocardial Infarction 36) trial. AB - OBJECTIVES: We designed a prospective evaluation of the interaction between B type natriuretic peptide (BNP) and the effect of ranolazine in patients with acute coronary syndromes (ACS) as part of a randomized, blinded, placebo controlled trial. BACKGROUND: Ranolazine is believed to exert anti-ischemic effects by reducing myocardial sodium and calcium overload and consequently ventricular wall stress. BNP increases in response to increased wall stress and is a strong risk indicator in ACS. METHODS: We measured plasma BNP in all available baseline samples (n = 4,543) among patients with non-ST-segment elevation ACS randomized to ranolazine or placebo in the MERLIN-TIMI 36 (Metabolic Efficiency With Ranolazine for Less Ischemia in Non-ST Elevation Acute Coronary-Thrombolysis In Myocardial Infarction 36) trial and followed them for a mean of 343 days. The primary end point was a composite of cardiovascular death, myocardial infarction, and recurrent ischemia. BNP elevation was defined as >80 pg/ml. RESULTS: Patients with elevated BNP (n = 1,935) were at significantly higher risk of the primary trial end point (26.4% vs. 20.4%, p < 0.0001), cardiovascular death (8.0% vs. 2.1%, p < 0.001), and myocardial infarction (10.6% vs. 5.8%, p < 0.001) at 1 year. In patients with BNP >80 pg/ml, ranolazine reduced the primary end point (hazard ratio [HR]: 0.79; 95% confidence interval [CI]: 0.66 to 0.94, p = 0.009). The effect of ranolazine in patients with BNP >80 pg/ml was directionally similar for recurrent ischemia (HR: 0.78; 95% CI: 0.62 to 0.98; p = 0.04) and cardiovascular death or myocardial infarction (HR: 0.83; 95% CI: 0.66 to 1.05, p = 0.12). There was no detectable effect in those with low BNP (p interaction value = 0.05). CONCLUSIONS: Our findings indicate that ranolazine may have enhanced efficacy in high-risk patients with ACS identified by increased BNP. The interaction of biomarkers of hemodynamic stress and the effects of ranolazine warrants additional investigation. (Metabolic Efficiency With Ranolazine for Less Ischemia in Non-ST Elevation Acute Coronary Syndromes; NCT00099788). PMID- 20298925 TI - Biomarker bonanza? PMID- 20298926 TI - Effect of cyclosporine on left ventricular remodeling after reperfused myocardial infarction. AB - OBJECTIVES: This study examined the effect of a single dose of cyclosporine administered at the time of reperfusion on left ventricular (LV) remodeling and function by cardiac magnetic resonance 5 days and 6 months after myocardial infarction. BACKGROUND: In a human study, administration of cyclosporine at the time of acute reperfusion was associated with a smaller infarct size. METHODS: Twenty-eight patients of the original cyclosporine study had an acute (at 5 days) and a follow-up (at 6 months) cardiac magnetic resonance study to determine LV volumes, mass, ejection fraction, myocardial wall thickness in infarcted and remote noninfarcted myocardium, and infarct size. RESULTS: There was a persistent reduction in infarct size at 6 months in the cyclosporine group compared with the control group of patients (29 +/- 15 g vs. 38 +/- 14 g; p = 0.04). There was a significant reduction of LV end-systolic volume (and a trend for LV end-diastolic volume; p = 0.07) in the cyclosporine group compared with the control group, both at 5 days and 6 months after infarction. There was no significant difference between the 2 groups in either global LV mass or regional wall thickness of the remote noninfarcted myocardium at 5 days or 6 months. Attenuation of LV dilation and improvement of LV ejection fraction by cyclosporine at 6 months were correlated with infarct size reduction. CONCLUSIONS: Cyclosporine used at the moment of acute myocardial infarction reperfusion persistently reduces infarct size and does not have a detrimental effect on LV remodeling. These results are preliminary and must be supported by further studies. (Ciclosporin A and Acute Myocardial Infarction; NCT00403728). PMID- 20298927 TI - Reperfusion injury putting the genie back in the bottle? PMID- 20298928 TI - Atorvastatin causes insulin resistance and increases ambient glycemia in hypercholesterolemic patients. AB - OBJECTIVES: We investigated whether atorvastatin might decrease insulin sensitivity and increase ambient glycemia in hypercholesterolemic patients. BACKGROUND: Clinical trials suggest that some statin treatments might increase the incidence of diabetes despite reductions in low-density lipoprotein (LDL) cholesterol and improvement in endothelial dysfunction. METHODS: A randomized, single-blind, placebo-controlled parallel study was conducted in 44 patients taking placebo and in 42, 44, 43, and 40 patients given daily atorvastatin 10, 20, 40, and 80 mg, respectively, during a 2-month treatment period. RESULTS: Atorvastatin 10, 20, 40, and 80 mg significantly reduced LDL cholesterol (39%, 47%, 52%, and 56%, respectively) and apolipoprotein B levels (33%, 37%, 42%, and 46%, respectively) after 2 months of therapy when compared with either baseline (all p < 0.001 by paired t test) or placebo (p < 0.001 by analysis of variance [ANOVA]). Atorvastatin 10, 20, 40, and 80 mg significantly increased fasting plasma insulin (mean changes: 25%, 42%, 31%, and 45%, respectively) and glycated hemoglobin levels (2%, 5%, 5%, and 5%, respectively) when compared with either baseline (all p < 0.05 by paired t test) or placebo (p = 0.009 for insulin and p = 0.008 for glycated hemoglobin by ANOVA). Atorvastatin 10, 20, 40, and 80 mg decreased insulin sensitivity (1%, 3%, 3%, and 4%, respectively) when compared with either baseline (p = 0.312, p = 0.008, p < 0.001, and p = 0.008, respectively, by paired t test) or placebo (p = 0.033 by ANOVA). CONCLUSIONS: Despite beneficial reductions in LDL cholesterol and apolipoprotein B, atorvastatin treatment resulted in significant increases in fasting insulin and glycated hemoglobin levels consistent with insulin resistance and increased ambient glycemia in hypercholesterolemic patients. (Effects of Atorvastatin on Adiponectin Levels and Insulin Sensitivity In Hypercholesterolemic Patients; NCT00745836). PMID- 20298929 TI - Reverse remodeling of the atria after treatment of chronic stretch in humans: implications for the atrial fibrillation substrate. AB - OBJECTIVES: The aim of this report was to study the effect of chronic stretch reversal on the electrophysiological characteristics of the atria in humans. BACKGROUND: Atrial stretch is an important determinant for atrial fibrillation. Whether relief of stretch reverses the substrate predisposed to atrial fibrillation is unknown. METHODS: Twenty-one patients with mitral stenosis undergoing mitral commissurotomy (MC) were studied before and after intervention. Catheters were placed at multiple sites in the right atrium (RA) and sequentially within the left atrium (LA) to determine: effective refractory period (ERP) at 10 sites (600 and 450 ms) and P-wave duration (PWD). Bi-atrial electroanatomic maps determined conduction velocity (CV) and voltage. In 14 patients, RA studies were repeated >or=6 months after MC. RESULTS: Immediately after MC, there was significant increase in mitral valve area (2.1 +/- 0.2 cm(2), p < 0.0001) with decrease in LA (23 +/- 7 mm Hg to 10 +/- 4 mm Hg, p < 0.0001) and pulmonary arterial pressures (38 +/- 16 mm Hg to 27 +/- 12 mm Hg, p < 0.0001) and LA volume (75 +/- 20 ml to 52 +/- 18 ml, p < 0.0001). This was associated with reduction in PWD (139 +/- 19 ms to 135 +/- 20 ms, p = 0.047), increase in CV (LA: 1.3 +/- 0.3 mm/ms to 1.7 +/- 0.2 mm/ms, p = 0.006; and RA: 1.0 +/- 0.1 mm/ms to 1.3 +/- 0.3 mm/ms, p = 0.002) and voltage (LA: 1.7 +/- 0.6 mV to 2.5 +/- 1.0 mV, p = 0.005; and RA: 1.8 +/- 0.6 mV to 2.2 +/- 0.7 mV, p = 0.09), and no change in ERP. Late after MC, mitral valve area remained at 2.1 +/- 0.3 cm(2) (p = 0.7) but with further decrease in PWD (113 +/- 19 ms, p = 0.04) and RA ERP (at 600 ms, p < 0.0001), with increase in CV (1.0 +/- 0.1 mm/ms to 1.3 +/- 0.2 mm/ms, p = 0.006) and voltage (1.8 +/- 0.7 mV to 2.8 +/- 0.6 mV, p = 0.002). CONCLUSIONS: The atrial electrophysiologic and electroanatomic abnormalities that result from chronic stretch due to MS reverses after MC. These observations suggest that the substrate predisposing to atrial arrhythmias might be reversed. PMID- 20298930 TI - Sustained inflammation due to nuclear factor-kappa B activation in irradiated human arteries. AB - OBJECTIVES: The aim of this study was to investigate gene expression networks related to cardiovascular disease in radiated human arteries. BACKGROUND: Recent epidemiological studies have shown that radiotherapy is associated with cardiovascular disease years after treatment. However, the molecular mechanisms underlying late effects of radiation are poorly described. METHODS: Arterial biopsies from radiated and nonradiated human conduit arteries, from the same patient, were simultaneously harvested during microvascular free tissue transfer for cancer-reconstruction in 13 patients, 4 to 500 weeks from radiation treatment. Radiated and nonradiated arteries were compared, with Affymetrix (Santa Clara, California) microarrays on a subset of the material to generate candidate genes. A Taqman (Applied Biosystems, Foster City, California) low density array of 45 selected genes was designed for analysis of the whole material. RESULTS: Thirteen genes were synchronously expressed in all patients (p = 0.0015), including CCL8, CCL3, CXCL2, DUSP5, FGFR2, HMOX1, HOXA9, IL-6, MMP-1, PTX3, RDH10, SOD2, and TNFAIP3. A majority of differentially regulated genes related to the nuclear factor-kappa B (NF-kappaB) signaling pathway and were dysregulated even years after radiation. The NF-kappaB activation was confirmed by immunohistochemistry and immunofluorescence. CONCLUSIONS: In the present study, we found sustained inflammation due to NF-kappaB activation in human radiated arteries. The results are supported by previous in vitro findings suggesting that deoxyribonucleic acid injury, after radiation, activates NF kappaB. We also suggest that HOXA9 might be involved in the regulation of NF kappaB activation. The observed sustained inflammatory response can explain cardiovascular disease years after radiation. PMID- 20298931 TI - Understanding radiation-induced vascular disease. PMID- 20298932 TI - Effect of an antimicrobial agent on atherosclerotic plaques: assessment of metalloproteinase activity by molecular imaging. AB - OBJECTIVES: Technetium-99m-labeled matrix metalloproteinase inhibitor (MPI) was used for the noninvasive assessment of matrix metalloproteinase (MMP) activity in atherosclerotic plaques after minocycline (MC) intervention. BACKGROUND: MMP activity in atherosclerosis contributes to plaque instability. Some antimicrobial agents may attenuate MMP activity. METHODS: Atherosclerotic lesions were produced in 38 rabbits with a high cholesterol diet for 4 months; 5 groups of rabbits, in the fourth month, received fluvastatin (FS) (n = 6), low-dose MC (n = 7), high dose MC (n = 7), a combination of low-dose MC and FS (n = 6), or no intervention (n = 12); 8 unmanipulated rabbits were used as disease controls. Micro-single photon emission computed tomography imaging was performed in all animals after intravenous MPI administration, followed by pathologic characterization of the aorta. A cell culture study evaluated the effect of MC on MMP production by activated human monocytes. RESULTS: MPI uptake was visualized best in untreated atherosclerotic animals (percent injected dose per gram MPI uptake, 0.11 +/- 0.04%). MPI uptake was reduced in the FS (0.06 +/- 0.01%; p < 0.0001), high-dose MC (0.05 +/- 0.01%; p < 0.0001), and MC-FS (0.05 +/- 0.005%; p < 0.0001) groups. Low-dose MC did not resolve MPI uptake significantly (0.08 +/- 0.02; p = 0.167). There was no incremental benefit of the combination of MC and FS. MPI uptake showed a significant correlation with plaque MMP-2, and MMP-9 activity. MMP-9 release from tumor necrosis factor-alpha-activated macrophages was abrogated by incubation with MC. CONCLUSIONS: Molecular imaging of MMP activity in atherosclerotic plaque allows for the study of the efficacy of therapeutic interventions. MC administration resulted in substantial reduction in plaque MMP activity and histologically verified plaque stabilization. MC was found to be equally effective as FS. PMID- 20298933 TI - Improvement in cardiac function with small intestine extracellular matrix is associated with recruitment of C-kit cells, myofibroblasts, and macrophages after myocardial infarction. AB - OBJECTIVES: This study tested the hypothesis that modulation of angiogenesis and cardiac function by injecting small intestine extracellular matrix emulsion (EMU) into myocardium is associated with recruitment of c-kit cells, myofibroblasts, and macrophages after myocardial infarction. BACKGROUND: Degradation of native extracellular matrix has been associated with adverse cardiac remodeling after infarction. METHODS: Sixty-four rats were subjected to 45 min ischemia followed by 3, 7, 21, and 42 days of reperfusion, respectively. Saline or EMU (30 to 50 microl) was injected into the area at risk myocardium after reperfusion. Histological examination was performed by immunohistochemical staining, and cardiac function was analyzed using echocardiography. RESULTS: The population of c-kit-positive cells in infarcted myocardium with the EMU injection increased significantly relative to the saline control at 7 days of reperfusion. Along with this change, alpha-smooth muscle actin expressing myofibroblasts and macrophages accumulated to a significant extent compared with the saline control. Increased vascular endothelial growth factor protein level and strong immunoreactivity of vascular endothelial growth factor expression were observed. Angiogenesis in the EMU area was significantly enhanced relative to the saline control, evidenced by increased density of alpha-smooth muscle actin positive vessels. Furthermore, echocardiography showed significant improvements in fractional shortening, ejection fraction, and stroke volume in the EMU group. The wall thickness of the infarcted middle anterior septum in the EMU group was significantly increased relative to the saline control. CONCLUSIONS: We show for the first time that injection of EMU into the infarcted myocardium increases neovascularization and preserves cardiac function, potentially mediated by enhanced recruitment of c-kit positive cells, myofibroblasts, and macrophages. PMID- 20298934 TI - The National Heart, Lung, and Blood Institute bench to bassinet Program: a new paradigm for translational research. PMID- 20298935 TI - Spontaneous recanalization of a coronary artery after thrombotic occlusion: in vivo demonstration with optical coherence tomography. PMID- 20298937 TI - Alpha-adrenergic coronary vasoconstriction in humans. PMID- 20298939 TI - Determinants of raised pulse pressure in women. PMID- 20298940 TI - Alternative interpretation of mitochondrial metabolic changes in atrial tissue of type II diabetic human heart. PMID- 20298941 TI - Statins in acute coronary syndromes and genetic insight. PMID- 20298943 TI - Mesenteric vascular disease: problems and progress. Introduction. PMID- 20298944 TI - Epidemiology of mesenteric vascular disease: clinical implications. AB - The overall incidence rate of acute mesenteric ischemia between 1970 and 1982, diagnosed at either autopsy or operation, in the population of Malmo, Sweden was estimated at 12.9/100,000 person-years. Autopsy rate was 87%. Acute superior mesenteric artery (SMA) occlusion (embolus/thrombus ratio = 1.4), mesenteric venous thrombosis (MVT), and nonocclusive mesenteric ischemia (NOMI) were found in approximately 68%, 16%, and 16%, respectively. Acute SMA occlusion was found to be more common than ruptured abdominal aortic aneurysms. The incidence increased exponentially with age, equally distributed among men and women after adjusting for age and gender in the population. Thrombotic occlusions were located more proximally than embolic occlusions and intestinal infarction was more extensive, whereas patients with embolus had a higher frequency of acute myocardial infarction, and had cardiac thrombi in 48% and synchronous emboli in 68% of the patients. The proportion of patients with symptoms inherent with chronic mesenteric ischemia prior to onset of acute thrombotic occlusion has been reported to occur in 73%. Cardiac failure, history of atrial fibrillation, and recent surgery have all been associated with fatal NOMI. MVT is either caused by thrombophilia, direct injury, or local venous congestion or stasis. Multidetector row computed tomography with intravenous contrast enhancement and imaging in the arterial phase for suspicion of acute SMA occlusion and imaging in the venous phase for MVT has become the diagnostic method of choice. In-hospital mortality is highest for NOMI, lower for acute SMA occlusion, and lowest, around 20%, for MVT. PMID- 20298945 TI - Acute mesenteric ischemia: diagnostic approach and surgical treatment. AB - Mortality related to acute mesenteric arterial occlusion remains very high. Patient survival is dependent on prompt recognition and revascularization before ischemia progresses to intestinal gangrene. Biphasic computed tomography angiography has surpassed angiography as the diagnostic test of choice due to its ability to define the arterial anatomy and to evaluate secondary signs of mesenteric ischemia. Unlike chronic mesenteric ischemia, the treatment of acute arterial mesenteric ischemia, either embolic or thrombotic, remains largely surgical. This is due to the emergent need for revascularization combined with a careful evaluation of the intestines. Endovascular techniques remain useful, however, and can save precious time in the treatment of these challenging patients if integrated into a treatment pathway combined with definitive surgical treatment. A new hybrid endovascular-surgical treatment for the treatment of acute mesenteric thrombosis is described. PMID- 20298946 TI - Chronic mesenteric ischemia: how to select patients for invasive treatment. AB - Chronic mesenteric ischemia (CMI) remains a well-described disease process that is difficult to diagnose. Since its initial description more than a century ago, a myriad of diagnostic and treatment modalities have been applied to ameliorate the classic symptoms of postprandial abdominal pain and weight loss. It is estimated that mesenteric occlusive disease affects approximately 1% to 18% of the population, with a majority of these patients manifesting no symptoms of CMI. While associated with a small prevalence, the potential economic impact of this disease process, with the increasing age of the population and the catastrophic outcomes associated with no treatment, is significant. The primary etiology of CMI is atherosclerotic occlusive disease involving the ostia of the mesenteric arteries. Several studies have investigated the pathophysiology of the postprandial abdominal pain associated with ischemia focusing on transport mechanisms, claudication of the intestinal musculature, and ischemia of the visceral nerves. The process of diagnosing CMI involves assimilation of the presentation, typical history and physical examination findings, and results of imaging modalities. At the end of this diagnostic process, the decision to offer a patient surgical intervention is primarily based on symptomatology and results of duplex and other imaging modalities. There are specific criteria for which to offer symptomatic patients interventions. Patients who are asymptomatic do not need to undergo revascularization, which may disrupt collateral arterial circulation to the mesentery. They should be followed conservatively. PMID- 20298947 TI - Endovascular techniques in acute arterial mesenteric ischemia. AB - Rapid developments in preoperative noninvasive imaging as well as advanced endovascular techniques have made endovascular treatment of acute arterial mesenteric ischemia a feasible treatment option in many patients. Multidetector computed tomographic angiography will provide the diagnosis and guide treatment in most cases. The use of mechanical and aspiration embolectomy, sometimes in combination with thrombolytic therapy, is often successful in offering these very sick patients a good treatment option to open surgical revascularization. Underlying occlusive lesions can be treated in the same setting. Hybrid techniques using open abdominal exploration in combination with endovascular tools have the possibility of offering minimally invasive treatment to even more patients. Access to a hybrid operating room is very advantageous when performing these operations because it allows for performing both open and endovascular interventions in the same setting. A fixed angiographic system also minimizes radiation exposure and improves the imaging capabilities compared to a conventional, mobile C-arm. These tools must be used in conjunction with wise, careful clinical evaluation of the patient. PMID- 20298948 TI - Open surgical treatment for chronic mesenteric ischemia in the endovascular era: when it is necessary and what is the preferred technique? AB - Treatment of chronic mesenteric ischemia has evolved during the last 2 decades. Endovascular treatment has first emerged as an alternative to bypass in the elderly or higher-risk patient, but has become the primary modality of treatment in most patients with suitable lesions, independent of their surgical risk. Open mesenteric revascularization with bypass or (rarely) endarterectomy still has an important role in the treatment of patients with more extensive disease, including long-segment or flush occlusions, small vessel size, multiple tandem lesions, and severe calcification. Our preference for open reconstruction in good risk patients with multivessel disease is a supraceliac aorta to celiac and superior mesenteric artery (SMA) bypass, whereas an iliac artery to SMA bypass or, occasionally, an infrarenal aortic to SMA bypass is used in the higher-risk group. In this article, we summarize the selection criteria, techniques, and outcomes of open mesenteric reconstruction in the endovascular era. PMID- 20298949 TI - Endovascular treatment of chronic arterial mesenteric ischemia: a changing perspective? AB - Endovascular treatment for chronic mesenteric ischemia is growing in popularity because of its lower periprocedural morbidity and mortality than open surgery. It is especially suitable for the high-risk surgical candidate and for those who have a poor nutritional state, although endovascular surgery may not be possible in patients with ostial occlusions or heavily calcified vessels. A positive response to angioplasty is helpful to secure a diagnosis in patients with slightly atypical symptoms. There are little data at present to suggest that primary stenting is better than angioplasty alone, but insertion of a stent may be valuable as a rescue procedure following dissection, vascular recoil, or thrombosis during angioplasty. The superior mesenteric artery is probably the most important vessel to treat but, where this is impossible, celiac or inferior mesenteric artery dilatation may have therapeutic benefit. However, there is some evidence at present favoring multiple, as opposed to single-vessel, angioplasty or stenting. Long-term patency is better after mesenteric bypass, which may be preferred in the younger and fitter patient. Treatment of the celiac artery compression syndrome is primarily surgical, but stent insertion may have a role as a secondary procedure where there is a residual stenosis after median arcuate ligament division. PMID- 20298950 TI - Nonocclusive mesenteric hypoperfusion syndromes: recognition and treatment. AB - The main focus when discussing acute or chronic mesenteric ischemia is on occlusive disease, arterial or venous. This article reviews present knowledge on mesenteric nonocclusive hypoperfusion syndromes. The following three clinical entities are reviewed: (1) Intraabdominal hypertension (IAH), or abdominal compartment syndrome (ACS), is important after ruptured abdominal aortic aneurysm repair. IAH >20 mm Hg occurs in approximately 50% of patients after open repair and in 20% after endovascular repair of ruptured abdominal aortic aneurysm, but these patients are different and no randomized data exists yet. A consensus issued by the World Society of Abdominal Compartment Syndrome provides guidance. Early conservative treatment of IAH and, alternatively, abdominal closure devices for leaving the abdomen partially open temporarily are discussed and a treatment algorithm is suggested. (2) Colonic ischemia after abdominal aortic surgery, its risk factors, clinical presentation, and treatment are discussed. A significant number of such patients develop IAH and reducing the abdominal perfusion pressure affects the left colon, the sentinel organ in these patients. (3) Nonocclusive mesenteric ischemia (NOMI); most often such patients suffer from severe cardiac failure requiring massive inotropic support. The condition is difficult to define. Early diagnosis with multidetector row computed tomography is a worthwhile alternative when angiography presents difficulties. A stenosis of the superior mesenteric artery is frequently enough that it should be ruled out because endovascular treatment can be lifesaving. New knowledge on these three different mesenteric hypoperfusion syndromes is reviewed. Success in treating these difficult patients is benefited from a multidisciplinary approach. PMID- 20298951 TI - Treatment of mesenteric vein thrombosis. AB - Mesenteric vein thrombosis has a similar clinical course as arterial, although more prolonged. In the majority of cases conventional anticoagulant treatment should be used and is often successful. The duration should be at least 6 months. Thrombolysis has been used, both systemic and local, although only in small series. Surgery is indicated when there is peritonitis, when often bowel resection is necessary. Thrombectomy has been used infrequently. PMID- 20298952 TI - [Pressure ulcers - management of pressure injuries]. PMID- 20298955 TI - Traumatic brain injury: time to end the silence. PMID- 20298957 TI - Complement-mediated cytotoxicity of antibodies to the GABA(B) receptor. PMID- 20298959 TI - Defining post-stroke pain: diagnostic challenges. PMID- 20298960 TI - Neurology at a distance. PMID- 20298963 TI - Clinical features, pathophysiology, and treatment of medication-overuse headache. AB - Medication-overuse headache (MOH) is a chronic headache disorder defined by the International Headache Society as a headache induced by the overuse of analgesics, triptans, or other acute headache compounds. The population-based prevalence of MOH is 0.7% to 1.7%. Most patients with MOH have migraine as their primary headache and overuse triptans or simple analgesics. The pathophysiology of MOH is still unknown. As well as psychological mechanisms such as operant conditioning, changes in endocrinological homoeostasis and neurophysiological changes have been observed in patients with MOH. Recently, a genetic susceptibility has been postulated. In most cases, treatment of MOH consists of abrupt withdrawal therapy and then initiation of an appropriate preventive drug therapy. There is no clear evidence on which method of withdrawal therapy is the most efficacious. Withdrawal symptoms can be treated with steroids; however, not all data support this concept. As MOH can severely affect the quality of life of patients, it needs to be recognised early to enable appropriate treatment to be initiated. PMID- 20298964 TI - Chronic inflammatory demyelinating polyradiculoneuropathy: diagnostic and therapeutic challenges for a treatable condition. AB - Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a chronic neuropathy of supposed immune origin. Understanding of its pathophysiology has recently improved, although its causes remain unclear. The classic presentation of CIDP includes sensory and motor symptoms in the distal and proximal segments of the four limbs with areflexia, evolving over more than 8 weeks. Raised protein concentrations in CSF and heterogeneous slowing of nerve conduction are typical of the condition. In addition to this usual phenotype, distribution of symptoms, disease course, and disability can be heterogeneous, leading to underdiagnosis of the disorder. Diagnosis is sometimes challenging and can require use of imaging and nerve biopsy. Steroids and intravenous immunoglobulin are effective, and plasma exchange can be helpful as rescue therapy. The usefulness of immunosuppressants needs to be established. The identification of specific diagnostic markers and new therapeutic strategies with conventional or targeted immunotherapy are needed to improve the outlook for patients with CIDP. PMID- 20298965 TI - Voltage-gated sodium channels as therapeutic targets in epilepsy and other neurological disorders. AB - Voltage-gated sodium channels (VGSCs) are key mediators of intrinsic neuronal and muscle excitability. Abnormal VGSC activity is central to the pathophysiology of epileptic seizures, and many of the most widely used antiepileptic drugs, including phenytoin, carbamazepine, and lamotrigine, are inhibitors of VGSC function. These antiepileptic drugs might also be efficacious in the treatment of other nervous system disorders, such as migraine, multiple sclerosis, neurodegenerative diseases, and neuropathic pain. In this Review, we summarise the structure and function of VGSCs and their involvement in the pathophysiology of several neurological disorders. We also describe the biophysical and molecular bases for the mechanisms of action of antiepileptic VGSC blockers and discuss the efficacy of these drugs in the treatment of epileptic and non-epileptic disorders. Overall, clinical and experimental data indicate that these drugs are efficacious for a range of diseases, and that the development of drugs with enhanced selectivity for specific VGSC isoforms might be an effective and novel approach for the treatment of several neurological diseases. PMID- 20298966 TI - Progressive multifocal leukoencephalopathy and other disorders caused by JC virus: clinical features and pathogenesis. AB - Progressive multifocal leukoencephalopathy (PML) is a rare but often fatal brain disease caused by reactivation of the polyomavirus JC. Knowledge of the characteristics of PML has substantially expanded since the introduction of combination antiretroviral therapy during the HIV epidemic and the development of immune reconstitution inflammatory syndrome (IRIS) in patients with PML. Recently, the monoclonal antibodies natalizumab, efalizumab, and rituximab--used for the treatment of multiple sclerosis, psoriasis, haematological malignancies, Crohn's disease, and rheumatic diseases--have been associated with PML. Additionally, the JC virus can also lead to novel neurological disorders such as JC virus granule cell neuronopathy and JC virus encephalopathy, and might also cause meningitis. The increasingly diverse populations at risk and the recent discovery of the presence of the JC virus in the grey matter invite us to reappraise the pathogenesis of this virus in the CNS. PMID- 20298967 TI - Natalizumab-associated progressive multifocal leukoencephalopathy in patients with multiple sclerosis: lessons from 28 cases. AB - BACKGROUND: Treatment of multiple sclerosis with natalizumab is complicated by rare occurrence of progressive multifocal leukoencephalopathy (PML). Between July, 2006, and November, 2009, there were 28 cases of confirmed PML in patients with multiple sclerosis treated with natalizumab. Assessment of these clinical cases will help to inform future therapeutic judgments and improve the outcomes for patients. RECENT DEVELOPMENTS: The risk of PML increases with duration of exposure to natalizumab over the first 3 years of treatment. No new cases occurred during the first two years of natalizumab marketing but, by the end of November, 2009, 28 cases had been confirmed, of which eight were fatal. The median treatment duration to onset of symptoms was 25 months (range 6-80 months). The presenting symptoms most commonly included changes in cognition, personality, and motor performance, but several cases had seizures as the first clinical event. Although PML has developed in patients without any previous use of disease modifying therapies for multiple sclerosis, previous therapy with immunosuppressants might increase risk. Clinical diagnosis by use of MRI and detection of JC virus in the CSF was established in all but one case. Management of PML has routinely used plasma exchange (PLEX) or immunoabsorption to hasten clearance of natalizumab and shorten the period in which natalizumab remains active (usually several months). Exacerbation of symptoms and enlargement of lesions on MRI have occurred within a few days to a few weeks after PLEX, indicative of immune reconstitution inflammatory syndrome (IRIS). This syndrome seems to be more common and more severe in patients with natalizumab-associated PML than it is in patients with HIV-associated PML. WHERE NEXT?: Diagnosis of natalizumab-associated PML requires optimised clinical vigilance, reliable and sensitive PCR testing of the JC virus, and broadened criteria for recognition of PML lesions by use of MRI, including contrast enhancement. Optimising the management of IRIS reactions will be needed to improve outcomes. Predictive markers for patients at risk for PML must be sought. It is crucial to monitor the risk incurred during use of natalizumab beyond 3 years. PMID- 20298969 TI - The worldwide societal costs of dementia: Estimates for 2009. AB - BACKGROUND: The purpose of this study was to update the previous estimate of the worldwide cost of dementia in 2005 to 2009. METHODS: The cost model is based on prevalence estimates, country and region-specific data on Gross Domestic Product per person and average wage, with results from previously published cost-of illness studies in different countries. Prevalence figures are updated to 2009 and costs were adjusted to 2009 constant US dollars ($). RESULTS: The total worldwide societal cost of dementia, based on a dementia population of 34.4 million demented persons, was estimated to $422 billion in 2009, including $142 billion for informal care (34%). CONCLUSIONS: The worldwide cost of dementia has increased by 34% (18% in fixed prices) between 2005 and 2009. PMID- 20298970 TI - Cerebrospinal fluid biomarker results in relation to neuropathological dementia diagnoses. AB - BACKGROUND: Clinical dementia diagnoses are not always consistent with neuropathological findings. As correct diagnosis is important for treatment and care, new diagnostic possibilities for dementia are in demand. Cerebrospinal fluid biomarkers should ideally be able to identify ongoing processes in the brain, but need to be further compared with neuropathological findings for evaluation of their diagnostic validity. METHODS: This study included 43 patients with a clinical dementia disorder. All patients were neuropathologically examined at the University Hospital in Lund, Sweden, during the years 2001-2008, and all had a lumbar puncture carried out as part of the clinical investigation during the time of cognitive impairment. RESULTS: Of eight patients, five with Alzheimer's disease had elevated total tau protein (T-tau) and decreased amyloid beta 1-42 protein (Abeta42), while both values for the other three patients were normal. Slightly elevated T-tau and/or decreased Abeta42 were also seen in several patients with other dementia diagnoses such as Lewy body disease, frontotemporal lobar degeneration and vascular dementia. Furthermore, T-tau levels did not differ markedly between patients with morphologically tau-positive and tau-negative frontotemporal lobar degeneration. Also, seven of nine patients with Creutzfeldt-Jacob disease exhibited pronounced elevation in T-tau concentration. CONCLUSION: From this rather limited study, being the first of its kind in Sweden, we may conclude that there is no perfect concordance between cerebrospinal fluid biomarker levels and pathological findings, which should be taken into account in the clinical diagnostic setting. PMID- 20298968 TI - Developing a national strategy to prevent dementia: Leon Thal Symposium 2009. AB - Among the major impediments to the design of clinical trials for the prevention of Alzheimer's disease (AD), the most critical is the lack of validated biomarkers, assessment tools, and algorithms that would facilitate identification of asymptomatic individuals with elevated risk who might be recruited as study volunteers. Thus, the Leon Thal Symposium 2009 (LTS'09), on October 27-28, 2009 in Las Vegas, Nevada, was convened to explore strategies to surmount the barriers in designing a multisite, comparative study to evaluate and validate various approaches for detecting and selecting asymptomatic people at risk for cognitive disorders/dementia. The deliberations of LTS'09 included presentations and reviews of different approaches (algorithms, biomarkers, or measures) for identifying asymptomatic individuals at elevated risk for AD who would be candidates for longitudinal or prevention studies. The key nested recommendations of LTS'09 included: (1) establishment of a National Database for Longitudinal Studies as a shared research core resource; (2) launch of a large collaborative study that will compare multiple screening approaches and biomarkers to determine the best method for identifying asymptomatic people at risk for AD; (3) initiation of a Global Database that extends the concept of the National Database for Longitudinal Studies for longitudinal studies beyond the United States; and (4) development of an educational campaign that will address public misconceptions about AD and promote healthy brain aging. PMID- 20298971 TI - Characterization of tau fibrillization in vitro. AB - BACKGROUND: The assembly of tau proteins into paired helical filaments, the building blocks of neurofibrillary tangles, is linked to neurodegeneration in Alzheimer's disease and related tauopathies. A greater understanding of this assembly process could identify targets for the discovery of drugs to treat Alzheimer's disease and related disorders. By using recombinant human tau, we have delineated events leading to the conversion of normal soluble tau into tau fibrils. METHODS: Atomic force microscopy and transmission electron microscopy methodologies were used to determine the structure of tau assemblies that formed when soluble tau was incubated with heparin for increasing lengths of time. RESULTS: Tau initially oligomerizes into spherical nucleation units of 18- to 21 nm diameter that appear to assemble linearly into nascent fibrils. Among the earliest tau fibrils are species that resemble a string of beads formed by linearly aligned spheres that with time seem to coalesce to form straight and twisted ribbon-like filaments, as well as paired helical filaments similar to those found in human tauopathies. An analysis of fibril cross sections at later incubation times revealed three fundamental axial structural features. CONCLUSIONS: By monitoring tau fibrillization, we showed that different tau filament morphologies coexist. Temporal changes in the predominant tau structural species suggest that tau fibrillization involves the generation of structural intermediates, resulting in the formation of tau fibrils with verisimilitude to their authentic human counterparts. PMID- 20298972 TI - Genetic variation at a single locus and age of onset for Alzheimer's disease. AB - This perspective article provides an opportunity to explain a new genetic finding for late-onset Alzheimer's disease (LOAD). It is specifically written for physicians and scientists who are interested in LOAD, but it may be relevant to those interested in identifying susceptibility variants for other complex diseases. The significant finding discussed here is that a variable-length, deoxythymidine homopolymer (poly-T) within intron 6 of the TOMM40 gene is associated with the age of onset of LOAD [Roses AD, Lutz MW, Amrine-Madsen H, Saunders AM, Crenshaw DG, Sundseth SS, et al. A TOMM40 variable-length polymorphism predicts the age of late-onset Alzheimer's disease. Pharmacogenomics J 2009 December 22;[Epublication ahead of print]. This result was obtained with a phylogenetic study of the genetic polymorphisms that reside within the linkage disequilibrium (LD) block that contains the TOMM40, APOE, and APOC1 genes from patients with LOAD and age-matched subjects without disease. Although the data will have diagnostic, prognostic, and therapeutic strategy implications, this perspective is meant to place the inheritance pattern for this "complex" human disease into context, and to highlight the potential utility of applying phylogenetic tools to the study of the genetics of complex diseases. PMID- 20298973 TI - Commentary on "Developing a national strategy to prevent dementia: Leon Thal Symposium 2009." Creating a national database for successful aging. PMID- 20298974 TI - Commentary on "Developing a national strategy to prevent dementia: Leon Thal Symposium 2009." The rationale for a National Institutional Review Board for neurodegenerative diseases. AB - The published proceedings of the second Annual Leon Thal Symposium (Alzheimers Dement 2009;5:85-92) have added to the open discussion among leaders in this field, with respect to the development of a national strategy for accelerating the discovery of preventative interventions for Alzheimer's disease. One of the recommended "action steps" detailed in that report centers on the establishment of a National Institutional Review Board for neurodegenerative diseases. The purpose of this new ethical oversight panel would be to increase the efficiency with which large-scale multi-site trials are conducted. This essay expands on this recommendation, and two potential organizational models are briefly considered. A well-designed, highly-qualified, and responsive National Institutional Review Board for neurodegenerative diseases would serve the direct interest of protecting the rights, welfare, and safety of our older citizens, who so generously contribute their time, energy, and comfort to advance research to discover new treatments for this devastating disease. PMID- 20298976 TI - Commentary on "Developing a national strategy to prevent dementia: Leon Thal Symposium 2009." Is dementia among older individuals 75+ a unique disease? PMID- 20298977 TI - Commentary on "Developing a national strategy to prevent dementia: Leon Thal Symposium 2009." Methodologic considerations for preventing Alzheimer's disease by 2020. PMID- 20298975 TI - Commentary on "Developing a national strategy to prevent dementia: Leon Thal Symposium 2009." Dementia risk indices: A framework for identifying individuals with a high dementia risk. PMID- 20298978 TI - Commentary on "Developing a national strategy to prevent dementia: Leon Thal Symposium 2009." Developing a blood test for Alzheimer's disease using advanced genomic expression technology. AB - There is a significant need for reliable molecular biomarkers to aid in Alzheimer's disease (AD) clinical diagnosis. RNA transcriptional profiling, although extensively applied for biomarker development in other diseases, is first defining its role in AD. Application of this technology has the sensitivity and power to provide sufficient information for the development of tests to determine disease severity, progression, heterogeneity, and potential for therapeutic response in the AD population. In order to bring forth the potential of this technology, however, the community needs to make a concerted effort to begin sample collection as soon as patients/subjects are identified. Only then can these powerful technologies be applied in a well controlled study for the development of novel diagnostics. PMID- 20298979 TI - Design of comprehensive Alzheimer's disease centers to address unmet national needs. AB - The problem of Alzheimer's disease (AD) exemplifies the challenges of dealing with a broad range of aging-related chronic disorders that require long-term, labor-intensive, and expensive care. As the baby boom generation ages and brain diseases become more prevalent, the need to confront the pending health care crisis is more urgent than ever before. Indeed, there is now a critical need to expand significantly the national effort to solve the problem of AD, with special focus on prevention. The Campaign to Prevent Alzheimer's Disease by 2020 (PAD2020) aims to create a new paradigm for planning and supporting the organization of worldwide cooperative research networks to develop new technologies for early detection and treatments of aging-related memory and motor impairments. PAD 2020 is developing an implementation plan to justify (1) increasing the federal budget for research, (2) developing novel national resources to discover new interventions for memory and motor disorders, and (3) creating innovative and streamlined decision-making processes for selecting and supporting new ideas. Since 1978 the National Institute on Aging or National Institute of Health (NIH) established an extensive national network of AD research facilities at academic institutions including AD Centers (ADCs), Consortium to Establish a Registry for AD, AD Cooperative Study (ADCS), AD Drug Discovery Program, National Alzheimer's Coordinating Center, National Cell Repository for AD, and AD Neuroimaging Initiative. However, despite the success of these programs and their critical contributions, they are no longer adequate to meet the challenges presented by AD. PAD 2020 is designed to address these changes by improving the efficiency and effectiveness of these programs. For example, the ADCs (P30s and P50s) can be enhanced by converting some into Comprehensive Alzheimer's Disease Centers (CADCs) to support not only research, but also by being demonstration projects on care/treatment, clinical trials, and education as well as by seamlessly integrating multisite collaborative studies (ADCS, AD Neuroimaging Initiative, Patient Registries, Clinical Data Banks, etc) into a cohesive structure that further enhances the original mission of the National Institute on Aging ADCs. Regional CADCs offer greater efficiency and cost savings while serving as coordinating hubs of existing ADCs, thereby offering greater economies of scale and programmatic integration. The CADCs also broaden the scope of ADC activities to include research on interventions, diagnosis, imaging, prevention trials, and other longitudinal studies that require long-term support. Thus, CADCs can address the urgent need to identify subjects at high risk of AD for prevention trials and very early in the course of AD for clinical trials of disease modification. The enhanced CADCs will allow more flexibility among ADCs by supporting collaborative linkages with other institutions and drawing on a wider expertise from different locations. This perspective article describes the University of Pennsylvania (Penn) CADC Model as an illustrative example of how an existing ADC can be converted into a CADC by better utilization of Penn academic resources to address the wide range of problems concerning AD. The intent of this position paper is to stimulate thinking and foster the development of other or alternative models for a systematic approach to the study of dementia and movement disorders. PMID- 20298980 TI - Commentary on "Design of comprehensive Alzheimer's disease centers to address unmet national needs". PMID- 20298981 TI - 2010 Alzheimer's disease facts and figures. AB - Alzheimer's disease (AD) is the seventh leading cause of all deaths in the United States and is virtually tied with the sixth leading cause of death-diabetes. AD is the fifth leading cause of death in Americans aged 65 and older. Although other major causes of death have been on the decrease, deaths because of AD have been rising dramatically. Between 2000 and 2006, heart disease deaths decreased 11.1%, stroke deaths decreased 18.2%, and prostate cancer-related deaths decreased 8.7%, whereas deaths because of AD increased 46.1%. Older African Americans and Hispanics are more likely than older white Americans to have AD or other dementia. Current estimates are that African-Americans are about 2 times more likely, and Hispanics about 1.5 times more likely, than their white counterparts to have these conditions. However, the relationship of race and ethnicity to the development of AD and other dementias is complex and not fully understood. In 2009, nearly 11 million family and other unpaid caregivers provided an estimated 12.5 billion hours of care to persons with AD and other dementias; this care is valued at nearly $144 billion. Medicare payments for services to beneficiaries aged 65 years and older with AD and other dementias are three times higher than for beneficiaries without these conditions. Total payments for 2010 for health care and long-term care services for people aged 65 and older with AD and other dementias are expected to be $172 billion (not including the contributions of unpaid caregivers). An estimated 5.3 million Americans have AD; approximately 200,000 persons under age 65 with AD comprise the younger-onset AD population. Every 70 seconds, someone in America develops AD; by 2050 the time of every 70 seconds is expected to decrease to every 33 seconds. Over the coming decades, the baby boom population is projected to add 10 million people to these numbers. In 2050, the incidence of AD is expected to approach nearly a million people per year, with a total estimated prevalence of 11-16 million people. Dramatic increases in the numbers of "oldest old" (aged 85 years and older) across all racial and ethnic groups will also significantly affect the numbers of people living with AD. This report provides information to increase understanding of the public health effect of AD, including incidence and prevalence, mortality, costs of care, and effect on caregivers and society in general. This report also sets the stage for better understanding the relationship between race and ethnicity and the development of AD and other dementias. PMID- 20298982 TI - Letter to the editor on the 2009 Leon Thal Symposium. PMID- 20298983 TI - Recommendations for successful training on methods of delivery of biologics for cardiac regeneration: a report of the International Society for Cardiovascular Translational Research. AB - The field of myocardial regeneration (angiogenesis and myogenesis) might prove to play an important role in the future management of cardiovascular disease. Stem cells are currently undergoing testing in Phase I and Phase II clinical trials. Methods of delivery will affect the outcome of such therapies, perhaps significantly. This document provides suggested guidance in 4 methods of delivery: endocardial, intracoronary, coronary sinus, and epicardial. PMID- 20298984 TI - The impact of transcatheter atrial septal defect closure in the older population: a prospective study. AB - OBJECTIVES: We sought to prove that device closure of atrial septal defect (ASD) in older patients not only improves cardiac function but also results in symptomatic relief by improving functional class. BACKGROUND: Atrial septal defect accounts for approximately 10% of all congenital cardiac defects. It is possible that ASD closure in older patients may derive benefits, though this is not well established. We therefore aim to prospectively assess the clinical status and functional class of older patients after transcatheter ASD closure. METHODS: This was a prospective study of all patients age 40 years or more who underwent device closure of a secundum ASD between April 2004 and August 2006. Investigations including atrial and brain natriuretic peptide levels, electrocardiography, chest X-ray, transthoracic echocardiogram, 6-min walk test, and quality of life questionnaire were performed before and at 6 weeks and 1 year after the procedure. RESULTS: Twenty-three patients (median age 70 years, 13 women) had transcatheter device closure of ASD. Median ASD size was 18 mm (range 9 to 30 mm). Median pulmonary artery pressure was 22 mm Hg (range 12 to 27 mm Hg). At 1 year, New York Heart Association functional class improved (p = 0.004) in 16 patients with significant improvement in 6-min walk-test distance (p = 0.004) and physical (p = 0.002) as well as mental health score (p = 0.03). There were no major complications. One year following closure there was a significant change in left ventricular end-diastolic (p = 0.001) and end-systolic dimensions (p = 0.001) and also significant reduction in right ventricular end-diastolic dimension (p < 0.001). CONCLUSIONS: Our data demonstrated that ASD closure at advanced age results in favorable cardiac remodeling and improvement of functional class. PMID- 20298985 TI - Primary transcatheter patent foramen ovale closure is effective in improving migraine in patients with high-risk anatomic and functional characteristics for paradoxical embolism. AB - OBJECTIVES: In the present study, we sought to assess the effectiveness of migraine treatment by means of primary patent foramen ovale (PFO) transcatheter closure in patients with anatomical and functional characteristics predisposing to paradoxical embolism without previous cerebral ischemia. BACKGROUND: The exact role for transcatheter closure of PFO in migraine therapy has yet to be elucidated. METHODS: We enrolled 86 patients (68 female, mean age 40.0 +/- 3.7 years) referred to our center over a 48-month period for a prospective study to evaluate severe, disabling, medication-refractory migraine and documented PFO. The Migraine Disability Assessment Score (MIDAS) was used to assess the incidence and severity of migraine. Criteria for intervention included all of the following: basal shunt and shower/curtain shunt pattern on transcranial Doppler and echocardiography, presence of interatrial septal aneurysm and Eustachian valve, 3 to 4 class MIDAS score, coagulation abnormalities, and medication refractory migraine with or without aura. RESULTS: On the basis of our inclusion criteria, we enrolled 40 patients (34 females, mean age 35.0 +/- 6.7 years, mean MIDAS 35.8 +/- 4.7) for transcatheter PFO closure; the remainder continued on previous medical therapy. Percutaneous closure was successful in all cases, with no peri-procedural or in-hospital complications. After a mean follow-up of 29.2 +/- 14.8 months (range 6 to 48 months), PFO closure was complete in 95%; all patients (100%) reported improved migraine symptomatology (mean MIDAS score 8.3 +/- 7.8, p < 0.03). Specifically, auras were eliminated in 100% of patients after closure. CONCLUSIONS: Primary transcatheter PFO closure resulted in a very significant reduction in migraine in patients satisfying our criteria. PMID- 20298986 TI - Patent foramen ovale closure for migraine prevention: the subject is still open. PMID- 20298987 TI - Indications and outcomes of surgical closure of ventricular septal defect in adults. AB - OBJECTIVES: We sought to review our experience with surgical ventricular septal defect (VSD) closure in adults. BACKGROUND: Outcome data of VSD closure in adults on which to base recommendations are limited. Guidelines recommend closure of adult VSD for a Q(p)/Q(s) ratio > or =2, left ventricular volume overload, or endocarditis. METHODS: We retrospectively reviewed 46 patients (mean age 33.6 +/- 11.2 years, 24 women) who underwent surgical VSD closure (1958 to 2008). RESULTS: VSDs were classified according to the Society of Thoracic Surgeons as type 2 (membranous, 72%) or type 1 (subarterial, 26%). Aortic regurgitation (AR) (28%), left ventricular dilation (20%), and pulmonary hypertension (20%) were the most common indications for closure. Associated lesions justified surgery in 39% of patients. There were no early deaths. Morbidity included 1 high-grade atrioventricular block requiring permanent pacemaker and a residual VSD in 7 patients. Late mortality was 5% (mean follow-up: 10.3 +/- 12.4 years). Patient survival did not differ from expected survival in a reference population (p = 0.75). Late residual VSDs were more common after suture closure (6 of 8 patients). Late moderate AR developed in 5 patients (4 with a type 1 VSD) with aortic valve or sinus of Valsalva repair. The use of intraoperative transesophageal echocardiography was associated with fewer residual VSDs and less > or = moderate tricuspid valve regurgitation and AR. CONCLUSIONS: Associated heart defects and AR were common indications for VSD closure in adults, which was performed with low mortality and morbidity. Patch closure and use of intraoperative transesophageal echocardiography improve surgical outcomes. Important residua emphasize the need for life-long informed follow-up. PMID- 20298988 TI - Carotid artery stenting with proximal cerebral protection for patients with angiographic appearance of string sign. AB - OBJECTIVES: The aim of this study was to assess the safety and effectiveness of carotid artery stenting (CAS) with proximal cerebral protection in patients showing string sign at carotid angiography. BACKGROUND: Presence of string sign is a well-known factor for adverse events in patients with severe carotid artery disease undergoing CAS. METHODS: We used retrospective analysis of a cohort of patients who underwent carotid angiography with the intention to undergo carotid stenting and had angiographically documented string sign in the target lesion. RESULTS: From October 2006 to August 2007, 25 patients (21 men and 4 women, mean age 70.9 +/- 8.7 years) presented with string sign during carotid angiography. This was 6.0% of a total of 416 patients studied during the time of the study. Twenty patients (80.0%) were symptomatic, and 5 (20.0%) were asymptomatic. Carotid artery stenting was performed successively in all patients. Proximal cerebral protection was applied in all but 1 patient. The 30-day death/stroke rate was 0%. At 12-month follow-up neurological events did not occur; 1 patient developed a nonfatal myocardial infarction, and another patient died from noncardiac cause. The 12-month death/stroke rate was 4.0%. CONCLUSIONS: Carotid stenting under proximal cerebral protection seems to be a feasible and safe procedure to manage patients with severe carotid stenosis in presence of angiographic string sign. Further prospective trials are required to prove efficacy of CAS in larger study populations. PMID- 20298989 TI - Functional occlusions of the carotid artery (string signs): to treat or not to treat? PMID- 20298990 TI - Fractional flow reserve and myocardial perfusion imaging in patients with angiographic multivessel coronary artery disease. AB - OBJECTIVES: The aim of this study was to investigate the correlation between myocardial ischemia detected by myocardial perfusion imaging (MPI) with single photon emission computed tomography with intracoronary pressure-derived fractional flow reserve (FFR) in patients with multivessel coronary disease at angiography. BACKGROUND: Myocardial perfusion imaging can underestimate the number of ischemic territories in patients with multivessel disease. However, there are limited data comparing MPI and FFR, a highly accurate functional index of myocardial ischemia, in multivessel coronary disease. METHODS: Sixty-seven patients (201 vascular territories) with angiographic 2- or 3-vessel coronary disease were prospectively scheduled to undergo within 2 weeks MPI (rest/stress adenosine) and FFR in each vessel. RESULTS: In 42% of patients, MPI and FFR detected identical ischemic territories (mean number of territories 0.9 +/- 0.8 for both; p = 1.00). In the remaining 36% MPI underestimated (mean number of territories; MPI: 0.46 +/- 0.6, FFR: 2.0 +/- 0.6; p < 0.001) and in 22% overestimated (mean number of territories; MPI: 1.9 +/- 0.8, FFR: 0.5 +/- 0.8; p < 0.001) the number of ischemic territories in comparison with FFR. There was poor concordance between the ability of the 2 methods to detect myocardial ischemia on both a per-patient (kappa = 0.14 [95% confidence interval: -0.10 to 0.39]) and per-vessel (kappa = 0.28 [95% confidence interval: 0.15 to 0.42]) basis. CONCLUSIONS: Myocardial perfusion imaging with single-photon emission computed tomography has poor concordance with FFR and tends to underestimate or overestimate the functional importance of coronary stenosis seen at angiography in comparison with FFR in patients with multivessel disease. These findings might have important consequences in using MPI to determine the optimal revascularization strategy in patients with multivessel coronary disease. PMID- 20298991 TI - Decision making in multivessel coronary disease: the need for physiological lesion assessment. PMID- 20298992 TI - Point-of-care assessment of platelet reactivity after clopidogrel to predict myonecrosis in patients undergoing percutaneous coronary intervention. AB - OBJECTIVES: We sought to evaluate the influence of platelet reactivity after clopidogrel, as assessed by the VerifyNow point-of-care assay (Accumetrics, San Diego, California), on myonecrosis in low-to-intermediate risk patients undergoing percutaneous coronary intervention (PCI). BACKGROUND: Inadequate platelet inhibition at the time of PCI is associated with a higher risk of recurrent ischemic events. METHODS: A total of 250 consecutive biomarker-negative patients treated with clopidogrel and undergoing elective PCI were enrolled. Cardiac biomarkers (creatine kinase-myocardial band and troponin I) were measured before and 8 and 24 h after intervention. Platelet reactivity after clopidogrel was assessed immediately before PCI by the VerifyNow P2Y12 point-of-care assay. High platelet reactivity (HPR) after clopidogrel was defined as a platelet reaction unit value > or =240. RESULTS: Patients with HPR (31% of the overall population) showed more frequent myonecrosis, with statistical significance with regard to creatine kinase-myocardial band elevation (35% vs. 20%; p = 0.011), and by trend with regard to troponin-I elevation (47% vs. 35%; p = 0.059). Incidence of periprocedural myocardial infarction was higher in patients with HPR, both by creatine kinase-myocardial band (13% vs. 4%; p = 0.011) and troponin-I definition (32% vs. 19%; p = 0.019). By multivariable analysis, HPR was an independent predictor of periprocedural myocardial infarction. CONCLUSIONS: Easily assessed by a point-of-care assay, HPR after clopidogrel is a frequent finding and is associated with increased risk of myonecrosis in low-to-intermediate risk patients undergoing planned PCI. PMID- 20298993 TI - Mortality and morbidity reduction by primary percutaneous coronary intervention is independent of the patient's age. AB - OBJECTIVES: The aim of this study was to obtain a valid estimate of the clinical effects of primary percutaneous coronary intervention (PPCI) in relation to age. BACKGROUND: Treatment with PPCI is most beneficial in high-risk myocardial infarction patients. Paradoxically, elderly patients, who are at increased risk of adverse outcome, are often withheld PPCI. METHODS: Individual patient data were obtained from 22 randomized trials (n = 6,763) evaluating the clinical effects of PPCI versus fibrinolysis (FL). Differences in 30-day death, repeat myocardial infarction, and stroke between patients randomized to FL and PPCI were determined in 5 age-strata: < or =50, >50 to 60, >60 to 70, >70 to 80, and >80 years. Treatment effects are reported as odds ratios (ORs) and 95% confidence intervals (CI). Multivariable logistic regression analyses, which included age x treatment interaction, were applied to examine evidence of heterogeneity in age specific ORs. RESULTS: Thirty-day death increased with increasing age and ranged from 1.1% (FL) and 1.8% (PPCI) in patients < or =50 years to 26.4% and 18.3% in patients >80 years of age. The point estimate of treatment effect (overall adjusted OR: 0.65; 95% CI: 0.52 to 0.79) was compatible with a mortality reduction favoring PPCI in all age-strata (except in patients < or =50 years of age), and 95% CIs were largely overlapping. There was no evidence of heterogeneity in ORs between age categories. Similar results were observed for repeat myocardial infarction and stroke. CONCLUSIONS: In this analysis of randomized trials, the reduction in clinical end points by PPCI was not influenced by age. Hence, age per se should not be considered an exclusion criterion for the application of PPCI. PMID- 20298995 TI - High-dose atorvastatin in acute coronary and cerebrovascular syndromes. PMID- 20298994 TI - Efficacy of high-dose atorvastatin loading before primary percutaneous coronary intervention in ST-segment elevation myocardial infarction: the STATIN STEMI trial. AB - OBJECTIVES: This study sought to determine the efficacy of high-dose atorvastatin in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI). BACKGROUND: Previous randomized trials have demonstrated that statin pre-treatment reduced major adverse cardiac events (MACEs) in patients with stable angina pectoris and acute coronary syndrome. However, no randomized studies have been carried out with STEMI patients in a primary PCI setting. METHODS: A total 171 patients with STEMI were randomized to 80-mg atorvastatin (n = 86) or 10-mg atorvastatin (n = 85) arms for pre-treatment before PCI. All patients were prescribed clopidogrel (600 mg) before PCI. After PCI, both groups were treated with atorvastatin (10 mg). The primary end point was 30-day incidence of MACE including death, nonfatal MI, and target vessel revascularization. Secondary end points included corrected thrombolysis in myocardial infarction frame count, myocardial blush grade, and ST segment resolution at 90 min after PCI. RESULTS: MACE occurred in 5 (5.8%) and 9 (10.6%) patients in the 80-mg and 10-mg atorvastatin pre-treatment arms, respectively (p = 0.26). Corrected thrombolysis in myocardial infarction frame count was lower in the 80-mg atorvastatin arm (26.9 +/- 12.3 vs. 34.1 +/- 19.0, p = 0.01). Myocardial blush grade and ST-segment resolution were also higher in the 80-mg atorvastatin arm (2.2 +/- 0.8 vs. 1.9 +/- 0.8, p = 0.02 and 61.8 +/- 26.2 vs. 50.6 +/- 25.8%, p = 0.01). CONCLUSIONS: High-dose atorvastatin pre-treatment before PCI did not show a significant reduction of MACEs compared with low-dose atorvastatin but did show improved immediate coronary flow after primary PCI. High-dose atorvastatin may produce an optimal result for STEMI patients undergoing PCI by improving microvascular myocardial perfusion. (Efficacy of High Dose AtorvaSTATIN Loading Before Primary Percutaneous Coronary Intervention in ST Elevation Myocardial Infarction [STATIN STEMI]; NCT00808717). PMID- 20298996 TI - Prior coronary artery bypass graft patients with ST-segment elevation myocardial infarction treated with primary percutaneous coronary intervention. AB - OBJECTIVES: We sought to compare outcomes in ST-segment elevation myocardial infarction (STEMI) patients undergoing primary percutaneous coronary intervention (PCI) with or without previous coronary artery bypass grafts (CABG). BACKGROUND: Limited information exists regarding procedural success and clinical outcomes of STEMI patients with CABG undergoing primary PCI. METHODS: The APEX-AMI (Assessment of Pexelizumab in Acute Myocardial Infarction) trial was a randomized, placebo-controlled trial of pexelizumab in STEMI patients with planned primary PCI: 128 of 5,745 (2.2%) patients had prior CABG. Clinical/procedural characteristics, culprit vessel (infarct-related artery [IRA]), and 90-day clinical outcomes were compared. RESULTS: Patients with previous CABG were more frequently men, older, had a higher incidence of comorbidities and multivessel disease. In patients with versus without prior CABG, PCI was performed less frequently, that is, 78.9% versus 93.9%; of those with prior CABG receiving PCI, Thrombolysis In Myocardial Infarction (TIMI) flow grade 3 was also restored less often, that is, 82.5% versus 91.6% (both p < 0.001). In prior CABG, there was a nearly even designation of the IRA as a bypass graft (n = 63) versus a native vessel (n = 55): IRA post-PCI TIMI flow grade 3 was achieved in 66.7% versus 88.0%, respectively (p = 0.043). Prior CABG patients had increased 90-day death and composite 90-day death/congestive heart failure/shock. Excess death remained significant after multivariable adjustment (hazard ratio: 1.9, 95% confidence interval: 1.08 to 3.33, p = 0.025). When prior CABG patients were stratified by the type of IRA, there was further discrimination of the increased 90-day death, that is, 19% bypass graft (n = 63) versus 5.7% native vessel (n = 55, p = 0.05), respectively. CONCLUSIONS: Prior CABG patients with STEMI are less likely to undergo acute reperfusion, have worse angiographic outcomes following primary PCI, and higher 90-day mortality. These findings are especially applicable when the IRA was a bypass graft. PMID- 20298998 TI - A vanishing lesion. PMID- 20298997 TI - Adjunctive transcutaneous ultrasound with thrombolysis: results of the PLUS (Perfusion by ThromboLytic and UltraSound) trial. AB - OBJECTIVES: We investigated whether transcutaneous ultrasound (TUS) augments coronary thrombolysis and achieves higher rates of Thrombolysis In Myocardial Infarction (TIMI) flow grade 3 and ST-segment resolution in patients with ST segment elevation myocardial infarction (STEMI). BACKGROUND: In animal coronary and peripheral artery thrombosis models, low-frequency TUS enhances and accelerates thrombolysis. METHODS: In a double-blind, randomized, controlled international clinical trial, 396 patients with STEMI < or =6 h were randomized to thrombolysis alone or thrombolysis plus TUS. The 60 minute TIMI flow grade, ST segment resolution (primary end points) and other angiographic, electrocardiographic, and clinical outcomes were compared between treatment groups. RESULTS: The trial was halted after Safety and Efficacy Monitoring Committee interim analysis that demonstrated lack of treatment efficacy. In total, 360 patients were evaluable for angiographic, electrocardiographic, or clinical end points. Sixty minutes after thrombolytic administration, the proportion of patients achieving TIMI flow grade 3 did not differ between TUS and control groups (40.7% vs. 48.5%, respectively; p = 0.10). Achievement of >50% ST segment resolution at 60 min did not differ between TUS and control groups (53.2% vs. 50.0%; p = 0.93). Thirty-day mortality and composite clinical events-death, reinfarction, recurrent ischemia, stroke, major bleed, left ventricular rupture (9.7 % vs. 10.2%; p = 0.88)-did not differ between TUS and control patients. CONCLUSIONS: Thrombolysis plus TUS failed to improve 60-min TIMI flow grade or ST segment resolution versus thrombolysis alone. PMID- 20298999 TI - Massive left pulmonary artery pseudoaneurysm in a young child. PMID- 20299000 TI - Intravascular ultrasound for assessment of coronary drug-eluting stent deployment: an evolving field in need of new criteria. PMID- 20299001 TI - The American "College" of Cardiology. PMID- 20299002 TI - Phenomenological approaches in the thermodynamics of mixed micelles with electric charges. AB - The stability of mixed micelles in general has been extensively studied by the molecular thermodynamic approaches as well as by the phenomenological or thermodynamic approaches. In this article, phenomenological approaches in the thermodynamics of charged mixed micelles, mostly on ionic/nonionic mixed micelles, are reviewed. The electrostatic interaction constitutes a main contribution to the excess free energy per monomer (in kT unit) g(ex) in the case of ionic/nonionic mixed micelles and the corresponding contribution is generally negative, known as the electric synergism. The origin of the electric synergism is shown to reside in positive curvatures of g(ex,el) (the electric part of g(ex)) when plotted against the mole fraction of the ionic species x. Two types of the micellar Gibbs-Duhem (MGD) relations with (type 1) or without (type 2) the contribution from counterions are discussed to clarify various confusions found in the literature. Effects of varying ionic strengths with the micelle composition in the case of charged mixed micelles without any supporting electrolyte are discussed and a relevant way to correct for the effects is proposed. For ionic/nonionic mixed micelles, the regular solution model (RSM) and some two-parameter models to overcome the limitations inherent to the RSM are discussed. For mixed micelles subject to type 2 MGD relation, hydrogen ion titrations could provide g(el) experimentally just as in the case of linear polyelectrolytes and for those micelles subject to RSM, the titration curve becomes a straight line. Useful information is presented originating from the thermodynamic analysis on the difference of the intrinsic proton dissociation constants between the micelle and the monomer. An analytical expression of the dependence of the degree of counterion binding on x is discussed in comparison with the molecular thermodynamic results. The Corrin-Harkins relation is compared with the degree of counterion binding for ionic/nonionic mixed micelles. Mixed micelles in the concentration range higher than the critical micelle concentration (cmc) are discussed for three cases, the general method of Funasaki Hada, the ideal mixing case, and the RSM. PMID- 20299004 TI - The effect of parental modeling of anxious behaviors and cognitions in school aged children: an experimental pilot study. AB - The current study tested: (1) the impact of parental modeling of anxious behaviors and cognitions on child anxiety level, anxious cognitions, desired avoidance, and objective performance using an experimental paradigm; and (2) whether the impact of parental modeling of anxious behaviors and cognitions differed by parent gender. Twenty-five parents (a random selection of 12 male and 13 female parents) participated with one of their children (ages 8-12 years; 56.0% male; 76.0% Caucasian). All children experienced two test conditions: an anxious condition in which their parent was trained to act anxiously before a planned spelling test and a non-anxious condition in which their parent was trained to act in a relaxed and confident manner before a planned spelling test. Results showed that, regardless of parent gender, children endorsed higher anxiety levels, anxious cognitions, and desired avoidance of the spelling test in the anxious relative to the non-anxious condition. Parental modeling of anxiety did not affect child spelling performance. Significant interaction effects indicated that fathers had a stronger impact on child anxiety level and cognitions than did mothers. Results highlight the importance of parental modeling and the potential role of both mothers and fathers in prevention and treatment for child anxiety. PMID- 20299005 TI - Classification of alcohol abuse by plasma protein biomarkers. AB - BACKGROUND: Biochemical diagnostics of ethanol intake would improve alcohol abuse treatment and have applications in clinical trial and public safety settings. Self-reporting of alcohol use has clinical utility but lacks the desired reliability. Previously, proposed single-analyte biochemical tests of alcohol intake suffer from low sensitivity and specificity or examine only acute drinking and have therefore seen limited clinical use. METHODS: To address this unmet need, plasma protein biomarker discovery and validation were performed with an alcohol self-administering nonhuman primate model system to develop a diagnostic that accurately classifies subjects into nondrinking, nonabusive drinking, and abusive drinking categories. RESULTS: A 17-plasma protein panel was determined that correctly classifies abusive drinking with 100% sensitivity and also differentiates any level of drinking from alcohol abstinence with 88% accuracy. CONCLUSIONS: The biomarker panel reflects changes in multiple organ systems and suggests robust changes in the plasma proteome with drinking that might serve as a sensitive and specific diagnostic test. The specific plasma proteins altered with alcohol self-administration might represent indicators of alcohol-induced stress on a variety of organ systems. PMID- 20299006 TI - Basal hypothalamic pituitary adrenal axis activity and hippocampal volumes: the SMART-Medea study. AB - BACKGROUND: It has frequently been hypothesized that high levels of glucocorticoids have deleterious effects on the hippocampus and increase risk for cognitive decline and dementia, but no large-scale studies in humans have examined the direct relation between hippocampal volumes and hypothalamic pituitary-adrenal axis activity. METHODS: Cross-sectional analyses within the Second Manifestations of ARTerial disease-Magnetic Resonance (SMART)-Medea study, an ancillary study to the SMART-MR study on brain changes on magnetic resonance imaging (MRI) among patients with arterial disease. In 575 patients (mean age 62 +/- 9 years), diurnal cortisol rhythm was assessed with six saliva samples, collected at awakening; at 30, 45, and 60 min thereafter; and at 10 pm and 11 pm. A low dose of dexamethasone (.5 mg) was administered at 11 pm, and saliva was sampled the next morning at awakening. Volumetric measurements of the hippocampus were performed on a three-dimensional fast field echo T1-weighted scan with isotropic voxels. RESULTS: Mean total relative hippocampal volume was 6.0 +/- .7 mL. Linear regression analyses, adjusted for age, sex, vascular risk factors, and global brain atrophy showed that participants with higher evening levels and higher awakening levels after dexamethasone had smaller hippocampal volumes [B per SD (4.2) increase = -.09 mL; 95% confidence interval -.15 to -.03 mL and B per SD (2.5) increase = -.07 mL; 95% confidence interval -.13 to -.01 mL, respectively]. The awakening response was not significantly associated with hippocampal volumes. CONCLUSIONS: In this population, higher evening cortisol levels and reduced suppression after dexamethasone were associated with smaller hippocampal volumes, independent of total brain volume. The cortisol response after awakening was not associated with hippocampal volume. PMID- 20299007 TI - Ambulatory and challenge-associated heart rate variability measures predict cardiac responses to real-world acute emotional stress. AB - BACKGROUND: Heart rate variability (HRV) measures homeostatic regulation of the autonomic nervous system in response to perturbation and has been previously shown to quantify risk for cardiac events. Despite known interactions among stress vulnerability, psychiatric illness, and cardiac health, however, this is the first study to our knowledge to compare directly the value of laboratory HRV in predicting autonomic modulation of real-world emotional stress. METHODS: We recorded electrocardiograms (ECG) on 56 subjects: first, within the laboratory and then during an acute emotional stressor: a first-time skydive. Laboratory sessions included two 5-min ECG recordings separated by one ambulatory 24-hour recording. To test the efficacy of introducing a mild emotional challenge, during each of the 5-min laboratory recordings, subjects viewed either aversive or benign images. Following the laboratory session, subjects participated in the acute stressor wearing a Holter ECG. Artifact-free ECGs (n = 33) were analyzed for HRV then statistically compared across laboratory and acute stress sessions. RESULTS: There were robust correlations (r = .7-.8) between the laboratory and acute stress HRV, indicating that the two most useful paradigms (long-term wake, followed by short-term challenge) were also most sensitive to distinct components of the acute stressor: the former correlated with the fine-tuned regulatory modulation occurring immediately prior and following the acute stressor, whereas the latter correlated with gross amplitude and recovery. CONCLUSIONS: Our results confirmed the efficacy of laboratory-acquired HRV in predicting autonomic response to acute emotional stress and suggest that ambulatory and challenge protocols enhance predictive value. PMID- 20299008 TI - Granular insular cortex inactivation as a novel therapeutic strategy for nicotine addiction. AB - BACKGROUND: Nicotine is the principal component of tobacco smoke, resulting in addiction, and recent evidence suggests that damage to the insular cortex (insula) disrupts tobacco addiction in human smokers. However, the effect of an inactivation of this structure in an animal model of nicotine addiction has yet to be evaluated. METHODS: To study this question, we investigated the effects of reversible inactivation of the granular insula by local injection of a gamma aminobutyric acid agonists mixture (baclofen/muscimol) on nicotine self administration (SA) under fixed and progressive ratio and on reinstatement of nicotine seeking induced by nicotine priming or nicotine-associated cues in rats. We also evaluated the effects of granular insula inactivation on food SA and relapse as a control. RESULTS: The inactivation of the granular insula decreased nicotine SA under both fixed and progressive ratios without affecting the SA of food under the same schedules of reinforcement. This inactivation also prevented the reinstatement, after extinction, of nicotine seeking induced by nicotine associated cues or nicotine priming without modifying the reinstatement of food seeking. CONCLUSIONS: Our study indicates that the integrity of the granular insula is necessary for exhibiting motivation to take nicotine and to relapse to nicotine seeking but not for consuming food pellets or to relapse for food seeking. Indeed, it might be interesting to study the effect of methods that are able to modulate the activity of the insula--such as repetitive transcranial magnetic stimulation or deep brain stimulation--on tobacco addiction and relapse in humans. PMID- 20299009 TI - IFNgamma primes macrophages for inflammatory activation by high molecular weight hyaluronan. AB - The objective was to assess outcomes of IFNgamma-priming upon macrophage activation by the synovial macromolecule high molecular weight hyaluronan [HMW HA] in the context of rheumatoid arthritis inflammation. Human macrophages primed by IFNgamma and activated by HMW-HA were evaluated for cytokine secretion by ELISA and Milliplex assay and activation profiles by nuclear transcription factor EIA. IFNgamma-primed, HMW-HA-activated macrophages produced elevated levels of TNF and secreted the TH1 cytokine IL-12p70, while IFNgamma suppressed HMW-HA induced secretion of the regulatory cytokine IL-10 and activation of the transcription factor c-Jun. IFNgamma modulates the HMW-HA-induced cytokine response profile promoting macrophage activation and inflammatory TH1 cytokine secretion. PMID- 20299010 TI - Leukocyte reactivity as an objective means of quantifying mental loading during ergonomic evaluation. AB - Psychological stress evokes rapid changes to the cardiovascular and neuroendocrine systems, responses that can become habituated following repeated exposure. This study, comprising of two phases, suggests that the immune system follows a similar trend. Phase 1: 15 healthy subjects (aged between 26 and 56years) provided capillary blood samples before and after completing three basic tasks using, in turn, two automotive touch screen interfaces (Interface 1 antecedent version, Interface 2-improved version). Using a chemiluminescent technique termed leukocyte coping capacity (LCC), the ability of leukocytes to produce reactive oxygen species in vitro was assessed. Significant differences in leukocyte activity were shown between treatment groups, where the greatest post test decrease occurred after using Interface 1. Phase 2: a randomly selected sub group (n=4) underwent weekly repeat testing using both interfaces. Significant differences in post-test leukocyte reactivity were exhibited between test weeks for each interface-the magnitude of response decreasing with successive exposure. PMID- 20299011 TI - Incidence and risk factors of non-fatal injuries in Chinese children aged 0-6 years: a case-control study. AB - AIM: To identify the incidence and related risk factors of injuries in pre-school children aged 0-6 years in China. METHODS: Children with non-fatal injuries (n=122) were matched to healthy controls by sex, age, community of residency and history of injury. Conditional multiple logistic regression analysis was performed to estimate the odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: The overall incidence of injuries was 3.3%. After adjustment for all selected variables, the risk factors for childhood injuries included father's occupation as a self-employed person (OR: 5.7, 95% CI: 1.8-18.5), child's active temperament type (OR: 2.8, 95% CI: 1.5-5.3), inappropriate storage of medicines (OR: 3.1, 95% CI: 1.3-6.9) and inappropriate placement of heating equipment (OR: 2.1, 95% CI: 1.0-4.4). The protective factors included children's acquirement of safety education from their teachers at school (OR: 0.03, 95% CI: 0.01-0.2), and from their parents (OR: 0.08, 95% CI: 0.02-0.3). CONCLUSIONS: Interventions targeting the risk factors specifically may help prevent and reduce the occurrence of injuries in young children. PMID- 20299012 TI - Problems with pelvic and acetabular fracture data. PMID- 20299013 TI - Interpreting patients as a means of clinical practice: introducing nursing hermeneutics. AB - BACKGROUND: The increased reference to hermeneutics from nursing scientists, researchers and academics has emphasized that interpretation has traditionally been a fundamental part of nursing practice. In nursing research a propensity for acquiring knowledge and understanding by using, multiple modalities has been demonstrated. In recent years, the use of hermeneutic phenomenology, has featured amongst these modalities. Hermeneutic phenomenology is an inquiry arm of, philosophical hermeneutics. OBJECTIVES: To explore the hypotheses that the patient can be considered as "text" and as such to be, interpreted in order to gain information for decision-making in clinical practice. DESIGN: A qualitative approach (hermeneutic phenomenological) to nursing clinical practice. SETTINGS: The clinical case of a patient suffering from cancer is described in the paper who was treated, in an Oncology Centre in Cyprus. METHODS: A hermeneutical model of clinical decision-making in nursing is implemented in practice. The, model was initially used in medical practice; however it finds applications to nursing as well. According, to the model, a patient is perceived as a literary text which may be interpreted on four levels: (1) the, literal facts of the patient's body and the literal story told by the patient, (2) the nursing diagnostic, meaning of the literal data, (3) the praxis (the nursing interventions) emanating from the nursing, diagnosis, and (4) the change effected by the clinical encounter in both the patient's and nurse's lifeworlds. RESULTS: Nursing interventions were successfully informed by the interpretation process. PMID- 20299014 TI - DNP=PhD-light, or old wine in new bottles? PMID- 20299015 TI - Column switching high-performance liquid chromatography with two channels electrochemical detection for high-sensitive determination of isoflavones. AB - Column switching HPLC with electrochemical detection (HPLC-ED), which consists of one pre-column and two electrochemical detectors subsequent to each analytical column, called HPLC-2ED, has been developed for determining isoflavones (daidzin, genistin, daidzein, and genistein) with high sensitivity. In the present HPLC 2ED, the eluted daidzin and genistin from the pre-column were separated on an analytical column using a methanol-water-phosphoric acid mixture (30:70:0.5) as the mobile phase (MP), and daidzein and genistein were separated on another analytical column using a methanol-water-phosphoric acid mixture (50:50:0.5). The way of the elute flow from the pre-column was changed by rotating the switching valve at 17 min. The difference in retention times of genistein between isocratic HPLC-ED and HPLC-2ED was 52.2 min. The detection limit (S/N=3) per column injection (5 microL) of genistein was 0.5 pg. The sensitivity by the present method is superior to that of previously reported gradient HPLC-ED for the determination of isoflavones. PMID- 20299016 TI - Preparation of a polyacrylonitrile/multi-walled carbon nanotubes composite by surface-initiated atom transfer radical polymerization on a stainless steel wire for solid-phase microextraction. AB - We report on the fabrication and performances of a solid-phase microextraction (SPME) fiber based on a stainless steel wire coated with a covalently attached polyacrylonitrile (PAN)/multi-walled carbon nanotubes (MWCNTs) composite. This new coating is obtained by atom transfer radical polymerization (ATRP) of acrylonitrile mixed with MWCNTs. ATRP is initiated from 11-(2-bromo-2 methylpropionyloxy)-undecyl-phosphonic acid molecules grafted on the wire surface via the phosphonic acid group. The extraction performances of the fibers are assessed on different classes of compounds (polar, non-polar, aromatic, etc.) from water solutions by headspace extraction. The optimization of the parameters affecting the extraction efficiency of the target compounds was studied as well as the reproducibility and the repeatability of the fiber. The fibers sustain more than 200 extractions during which they remain chemically stable and maintain good performances (detection limits lower than 2 microg/l, repeatability, etc.). Considering their robustness together with their easy and inexpensive fabrication, these fibers could constitute promising alternatives to existing products. PMID- 20299017 TI - Determination of 4-nonylphenol in water samples using 4-(2,6-dimethylhept-3 yl)phenol as new internal standard. AB - A new method for determining the endocrine disrupting substance 4-nonylphenol (technical grade=mixture of isomers, 4-NP) from water samples has been developed by using 4-(2,6-dimethylhept-3-yl)phenol (4-sec-NP) as model compound. This branched monoalkylphenol is shown to serve as internal standard (IS) for the determination of technical 4-nonylphenol. To the best of our knowledge, 4-(2,6 dimethylhept-3-yl)phenol (racemic mixture) is a newly synthesized 4-nonylphenol isomer and has not been described elsewhere. Recoveries have been determined by analyzing spiked water samples from distilled water, river water and wastewater. Following acetylation, the compounds were enriched via solid phase extraction (SPE). Analyses of the compounds were performed by capillary column gas chromatography/mass spectrometry (GC/MS), operating in selected ion-monitoring (SIM) mode. The recovery of technical 4-NP using either the newly prepared 4-sec NP or 4-n-nonylphenol (4-n-NP) as IS have been compared. 4-sec-NP showed slightly better results. However, in the first series of experiments using wastewater, the yields for the derivatization of the two standard compounds were remarkably different. The yield for derivatization of 4-n-NP was approximately 20%, probably due to the difficult matrix of the wastewater. In contrast, the yield for the derivatization of 4-sec-NP was considerably higher (approximately 63%). This problem can be solved by increasing the concentration of the reagent used for derivatization. For better control of the clean-up process, we recommend application of 4-sec-NP as internal standard, at least in water samples with complex matrices (e.g., high content of hydroxylated compounds). PMID- 20299018 TI - A novel method for the determination of total 1,3-octanediols in apple juice via 1,3-dioxanes by solid-phase microextraction and high-speed gas chromatography. AB - In this work, a novel, simple and fast method based on solid-phase microextraction (SPME) followed by high-speed gas chromatography (HSGC) was developed for the analysis of total 1,3-octanediols in apple juices by means of derivatization reaction to volatile 1,3-dioxanes. The derivatization reaction, SPME conditions, glycosidically bound fraction and 1,3-nonanediol as a surrogate standard were studied. The formation of 1,3-dioxanes from 1,3-diols was confirmed by GC-MS. The method was validated obtaining a regression coefficient (r(2)) of 0.9996, precisions between 0.3 and 9.8%, extraction recoveries in the range 94.7 112.2% and LOD of 2.9 microg l(-1). Experimental design has been employed in the optimization of extraction factors and robustness assessment. The method was applied to the analysis of 21 Asturian apple varieties finding a double reciprocal relationship between the concentrations of saturated and unsaturated 1,3-octanediol. PMID- 20299019 TI - Substituent effect on electrophoretic mobility for a series of poly(N-acryloyl amino acid)s. AB - In this study, the electrophoretic mobilities (mu) for a series of poly(N acryloyl-amino acid)s were determined by capillary zone electrophoresis to investigate the effect of substituent on the electrophoretic behavior of polyelectrolytes. The mu values determined showed a strong correlation with the molar volume of the corresponding amino acids. PMID- 20299020 TI - Chromatographic analysis. Foreword. PMID- 20299021 TI - Continuous solid-phase extraction and gas chromatography-mass spectrometry determination of pharmaceuticals and hormones in water samples. AB - A semi-automatic flow-based method for the simultaneous determination of 9 pharmaceuticals and 3 hormones in water samples in a single analytical run is proposed. The analytes were retained on a solid-phase extraction sorbent column and 1 microL of the eluate analysed by gas chromatography in combination with electron impact ionization mass spectrometry in the SIM mode. The sorbent used, Oasis-HLB, provided near-quantitative recovery of all analytes. The proposed method was validated with quite good analytical results including low limits of detection (0.01-0.06 ng L(-1) for 100 mL of water) and good linearity (r2>0.993) throughout the studied concentration ranges. The method provided good accuracy (recoveries of 85-103%) and precision (between- and within-day RSD values less than 7%) in the determination of the pharmaceuticals and hormones in tap, river, pond, well, swimming pool and wastewater. PMID- 20299022 TI - A review of analytical techniques for determination of Sudan I-IV dyes in food matrixes. AB - Sudan dyes are a family of lipophilic azo dyes, extensively used in industrial and scientific applications but banned for use as food colorants due to their carcinogenicity. Due to the continuing illicit use of Sudan dyes as food colorants their determination in different food matrices--especially in different chilli and tomato sauces and related products--has during the recent years received increasing attention all over the world. This paper critically reviews the published determination methods of Sudan I-IV dyes. LC-UV-vis and LC-MS are the dominating methods for analysis of Sudan I-IV dyes. Sudan dyes are usually found in food at mg kg(-1) levels at which it may be necessary to use a preconcentration step in order to attain the desired detection limits. Liquid solid extraction is the dominating sample preparation procedure. In recent years it has been supplemented by ultrasonic-assisted extraction and pressurized liquid extraction. Various solid phase extraction types have been used for sample cleanup. The large majority of works use conventional C18 columns and conventional LC eluents. Traditionally the UV-vis absorbance detection has been the most frequently used. In the recent years MS detection is applied more and more often as it offers more reliable identification possibilities. PMID- 20299023 TI - Coupling liquid chromatography to Orbitrap mass spectrometry. AB - The Orbitrap mass analyzer has become a mainstream mass spectrometry technique. In addition to providing a brief introduction to the Orbitrap technology and its continuing development, this article reviews the most recent publications quoting the use of the Orbitrap detection for a variety of chromatographic separation techniques. Its coupling to reversed-phase liquid chromatography (LC) represents undoubtedly the most ubiquitous approach to both small molecule and proteomic analyses. Multi-dimensional LC separations have an important role to play in the proteomics applications while an ultra-high-pressure LC is more frequently encountered in the area of metabolomics and metabolite analysis. Recently, special chromatographic techniques such as hydrophilic interaction chromatography and its variations have also been also cited with the Orbitrap detection. PMID- 20299024 TI - Selectable one-dimensional or two-dimensional gas chromatography-mass spectrometry with simultaneous olfactometry or element-specific detection. AB - A novel selectable one-dimensional (1D) or two-dimensional (2D) gas chromatography-mass spectrometry (selectable 1D/2D GC-MS) system with selective detection was developed by using capillary flow technology and low thermal mass GC (LTM-GC). The main advantages of this system are the simple and fast selection of 1D GC-MS or 2D GC-MS operation without any instrumental set-up change (e.g. 2D GC-MS can be run just after 1D GC-MS run), and simultaneous mass spectrometric and olfactometry or element-specific detection for both 1D and 2D separation to assure selection of a heart-cut region and correct identification of compounds of interest. The feasibility and benefit of the proposed system with selective detection, e.g. olfactometry, nitrogen phosphorus detection (NPD), and pulsed flame photometric detection (PFPD), was demonstrated with an identification of trace amounts of aroma components in beverages (beer and coffee). Using stir bar sorptive extraction (SBSE) and selectable 1D/2D GC-Olfactometry/MS on a beer sample, beta-damascenone could be determined at 1.9 ng mL(-1) (RSD 3.1%, n=6) as a potent aroma compound. In a coffee sample, two odor active compounds were clearly resolved from a 4.2 s heart-cut and were assigned probable identifications as 4,5-dimethyl thiazole and dimethyl trisulfide based on a NIST library search, dual linear retention indices (dual LRI) and elemental information obtained by SBSE in combination with selectable 1D/2D GC-NPD/PFPD/MS. PMID- 20299025 TI - Separation of intact proteins on porous layer open tubular (PLOT) columns. AB - Porous layer open tubular (PLOT) polystyrene divinylbenzene columns have been used for separating intact proteins with gradient elution. The 10 microm I.D. x 3 m columns were easily coupled to standard liquid chromatography-mass spectrometry (LC-MS) instrumentation with commercially available fittings. Standard proteins separated on PLOT columns appeared as narrow and symmetrical peaks with good resolution. Average peak width increased linearly with gradient time (tG) from 0.14 to 0.33 min (tG 20 and 120 min, respectively) using a 3 m column. With shorter columns, peak widths were larger and increased more steeply with gradient time. Theoretical peak capacity (nc) increased with column length (tested up to 3 m). The nc increased with tG until a plateau was reached. The highest peak capacity achieved (nc=185) was obtained with a 3 m column, where a plateau was reached with tG 90 min. The within- and between column retention time repeatabilities were below 0.6% and below 2.5% (relative standard deviation, RSD), respectively. The carry-over following injection of 0.5 ng per protein was less than 1.1%. The retention time dependence on column temperature was investigated in the range 20-50 degrees C. Proteins in a skimmed milk sample were separated using the method. PMID- 20299026 TI - 1-Butyl-3-methylimidazolium-based ionic liquids and an anionic surfactant: excellent background electrolyte modifiers for the analysis of benzodiazepines through capillary electrophoresis. AB - In this study, we found that adding 1-butyl-3-methylimidazolium-based ionic liquids (ILs) and sodium dodecyl sulfate (SDS) as modifiers in the background electrolyte (BGE) for capillary electrophoresis enhanced the separation of benzodiazepines. In particular, 1-butyl-3-methylimidazolium bis(trifluoromethanesulfonyl)imide ([BMIM][NTf2]) was the best IL additive for the separation system because its anionic moiety interacted favorably with the benzodiazepines. We added SDS because of its known effect on the separation of hydrophobic analytes. We optimized the separation conditions in terms of the concentrations of the IL, SDS, and organic solvent, the pH, and the BGE's ionic strength. The optimal BGE, containing 170 mM [BMIM][NTf2] and 10 mM SDS, provided baseline separation, high efficiency, and satisfactory peak shapes for the benzodiazepines. The separation mechanism was based on heteroassociation between the anionic moiety of the IL and the benzodiazepines, with SDS improving the resolution of the separation. The limits of detection for the seven analytes ranged from 2.74 to 4.42 microg/mL. We subjected a urine sample to off-line solid phase extraction (SPE) prior to the analysis of its benzodiazepine content. Our experimental results reveal that the combination of [BMIM][NTf2] and SDS provides adequate separation efficiency for its application to CE analyses of benzodiazepines after SPE concentration. PMID- 20299027 TI - Synthesis and application of a T-2 toxin imprinted polymer. AB - The synthesis of a T-2 toxin imprinted polymer and its application in food analysis are reported for the first time. A molecularly imprinted polymer (MIP) for the selective recognition of T-2 toxin (T-2) was synthesized by bulk polymerization. Methacrylamide and ethyleneglycol dimethacrylate were applied as functional monomer and cross-linker, respectively. Molecularly imprinted solid phase extraction (MISPE) procedures were optimized for further application in the analysis of T-2. Scatchard plot analysis revealed that two classes of imprinted binding sites were formed in the imprinted polymer. The dissociation constant (KD) of the higher affinity binding sites was 7.0 micromol/l, while the KD of the lower affinity binding sites was 54.7 micromol/l. The performance of the MIP throughout the clean-up of spiked maize, barley and oat sample extracts was compared with the results obtained when using non-imprinted polymer, OASIS HLB and immunoaffinity columns (IAC). Depending on the food matrix and the spiked concentration, recoveries after MISPE and non-imprinted solid-phase extraction varied respectively from 60% to 73% and from 21% to 57%. Recoveries obtained after clean-up using OASIS HLB and IAC were in the range of 74-104% and 60-85%, respectively. Although highest recoveries were obtained with OASIS HLB sorbents, the designed MIP and the IAC were superior regarding selectivity, cross reactivity, matrix effect, limits of detection (LOD) and limits of quantification (LOQ). Depending on the matrix, LOD after MISPE ranged from 0.4 microg/kg to 0.6 microg/kg and LOQ from 1.4 microg/kg to 1.9 microg/kg. LOD and LOQ after OASIS HLB clean-up varied from 0.9 microg/kg to 3.5 microg/kg and from 3.1 microg/kg to 11.7 microg/kg, respectively. The LOD and LOQ values obtained with IAC were in the range of 0.3-2.3 microg/kg and 1.0-7.7 microg/kg, respectively. Analysis of 39 naturally contaminated samples (maize, barley and oat) by liquid chromatography tandem mass spectrometry revealed that the MIP could be an excellent alternative for clean-up of contaminated food samples. PMID- 20299028 TI - Pulmonary vein isolation and autonomic denervation for the management of paroxysmal atrial fibrillation by a minimally invasive surgical approach. AB - BACKGROUND: Advances in technology such as epicardial bipolar radiofrequency pulmonary vein isolation, ganglionated plexi identification, and isolation and thoracoscopic left atrial appendage exclusion have enabled less invasive surgical options for management of atrial fibrillation. METHODS: We performed a prospective, nonrandomized study of consecutive patients with symptomatic paroxysmal atrial fibrillation undergoing a video-assisted, minimally invasive surgical ablation procedure. The procedure consisted of bilateral, epicardial pulmonary vein isolation with bipolar radiofrequency, partial autonomic denervation, and selective excision of the left atrial appendage. Minimum follow up was 1 year with long-term monitoring (24-hour continuous, 14-day event or pacemaker interrogation). RESULTS: Between March 2005 and January 2008, 52 patients (35 male), mean age 60.3 years (range, 42-79 years) underwent the procedure. The left atrial appendage was isolated in 88.0% (44/50). Average hospital stay was 5.2 days (range 3-10 days). There were no operative deaths or major adverse cardiac events. On long-term monitoring, freedom from atrial fibrillation/flutter/tachycardia was 86.3% (44/51) and 80.8% (42/52) at 6 and 12 months, respectively. Antiarrhythmic drugs were stopped in 33 of 37 patients and warfarin in 30 of 37 of the patients in whom ablation was successful at 12 months. Freedom from symptoms attributed to atrial fibrillation/flutter/tachycardia was 78.0% (39/50) at 6 months and 63.8% (30/47) at 12 months. CONCLUSIONS: Minimally invasive surgical ablation is effective in the management of paroxysmal atrial fibrillation as evidenced by freedom from atrial arrythmias by long-term monitoring at 12 months. Measuring success using clinical symptoms underestimated clinical success as compared with long-term monitoring. PMID- 20299029 TI - Fourteen years' experience with 501 subcoronary Ross procedures: surgical details and results. AB - OBJECTIVE: During the past decade the Ross procedure using the full root has become the predominant surgical technique. However, progressive autograft dilatation and eventual failure remain a concern. Here we report on the surgical techniques and results of the subcoronary technique over a 14-year period. METHODS: A total of 501 patients (mean age, 44.9 +/- 12.9 years; 117 female; 384 male) were operated on from June 1994 to December 2007. The follow-up database, with a completeness of 98.2%, was closed on December 2008, comprising of 2931 patient-years with a mean follow-up of 5.9 +/- 3.6 years (range, 0.1-14.1 years). RESULTS: Surgical details are presented. Early and late mortality were 0.4% (n = 2) and 4% (n = 20), respectively, valve-related mortality was 1.2% (n = 6), whereas the overall survival did not differ from that of the normal population. Neurologic events occurred in 22 patients, major bleeding in 9, autograft endocarditis in 8, and homograft endocarditis in 10. Freedom from autograft and homograft reoperation was 91.9% at 10 years. For the majority of patients, hemodynamics was excellent and no root dilatation was observed. CONCLUSIONS: Midterm results after the original subcoronary Ross procedure are excellent, including normal survival and low risk of valve-related morbidity. Longer-term results are necessary for continuous judgment of the subcoronary technique. PMID- 20299030 TI - Dor procedure for dyskinetic anteroapical myocardial infarction fails to improve contractility in the border zone. AB - BACKGROUND: Endoventricular patch plasty (Dor) is used to reduce left ventricular volume after myocardial infarction and subsequent left ventricular remodeling. METHODS AND RESULTS: End-diastolic and end-systolic pressure-volume and Starling relationships were measured, and magnetic resonance images with noninvasive tags were used to calculate 3-dimensional myocardial strain in 6 sheep 2 weeks before and 2 and 6 weeks after the Dor procedure. These experimental results were previously reported. The imaging data from 1 sheep were incomplete. Animal specific finite element models were created from the remaining 5 animals using magnetic resonance images and left ventricular pressure obtained at early diastolic filling. Finite element models were optimized with 3-dimensional strain and used to determine systolic material properties, T(max,skinned-fiber), and diastolic and systolic stress in remote myocardium and border zone. Six weeks after the Dor procedure, end-diastolic and end-systolic stress in the border zone were substantially reduced. However, although there was a slight increase in T(max,skinned-fiber) in the border zone near the myocardial infarction at 6 weeks, the change was not significant. CONCLUSIONS: The Dor procedure decreases end-diastolic and end-systolic stress but fails to improve contractility in the infarct border zone. Future work should focus on measures that will enhance border zone function alone or in combination with surgical remodeling. PMID- 20299031 TI - Feasibility of transapical aortic valve implantation guided by intracardiac ultrasound without angiography. PMID- 20299032 TI - In utero/neonatal torsion: observation versus prompt exploration. PMID- 20299033 TI - Scientific publications: let the reader beware. PMID- 20299034 TI - Mining databases--what can we learn? PMID- 20299035 TI - Impact of previous radiotherapy for prostate cancer on clinical outcomes of patients with bladder cancer. AB - PURPOSE: The impact of prostate cancer radiotherapy on the biological behavior of bladder cancer remains unclear. We compared the outcomes of patients with bladder cancer previously treated for prostate cancer with radiotherapy vs other treatment modalities. MATERIALS AND METHODS: We identified 144 patients diagnosed with bladder cancer between January 1992 and June 2007 with a previous prostate cancer diagnosis. Clinicopathological data and outcomes were compared between patients with irradiated (brachytherapy and/or external beam radiation therapy 83) and nonirradiated (androgen deprivation therapy, radical prostatectomy and/or surveillance 61) disease. RESULTS: Median time between prostate and bladder cancer diagnoses was longer in the irradiated vs nonirradiated group (59 months, IQR 25 to 88, vs 24 months, IQR 2 to 87, p = 0.007). Patients in the irradiated group presented with higher tumor grade (high 92% vs 77%, p = 0.016) and had progression to higher stage disease (muscle invasive 70% vs 43%, p = 0.001) than those in the nonirradiated group. Of the patients undergoing cystectomy those previously treated with radiation had a numerically higher rate of nonorgan confined disease (75% vs 56% for nonirradiated, p = 0.1). Among all patients with bladder cancer 5-year cancer specific survival was 73% (95% CI 59-87) for irradiated vs 83% (95% CI 71-95) for nonirradiated (p = 0.07). Median followup was 53 months (IQR 24 to 75). CONCLUSIONS: More time elapsed between prostate and bladder cancer diagnoses for patients treated with radiation, and these patients also presented with more advanced disease. Future studies are needed to further establish clinical differences in bladder cancer between irradiated and nonirradiated cases, and whether biological differences exist. PMID- 20299036 TI - Editorial comment. PMID- 20299037 TI - Association of angiogenesis related markers with bladder cancer outcomes and other molecular markers. AB - PURPOSE: We tested whether the altered immunohistochemical expression of angiogenesis related markers is associated with outcomes of patients with urothelial carcinoma of the bladder, and assessed the correlation of angiogenesis related markers with molecular markers commonly altered in urothelial bladder carcinoma. MATERIALS AND METHODS: Vascular endothelial growth factor, basic fibroblast growth factor and thrombospondin 1 expression data were collected, as were microvessel density data. Immunohistochemical staining was performed on specimens from 204 patients treated with radical cystectomy for urothelial carcinoma of the bladder. We also stained serial sections of the specimens for cyclin E1, cyclin D1, p53, p21, p27, pRB, Ki-67, Bcl-2, caspase-3, survivin and cyclooxygenase-2. We measured time to disease recurrence and cancer specific mortality, as well as the association with clinical and pathological features and other molecular markers. RESULTS: The altered expression of vascular endothelial growth factor (over expression), basic fibroblast growth factor (over expression) and thrombospondin 1 (decreased expression) was 86%, 79% and 63%, respectively. Median microvessel density was 20. All 4 markers were associated with established clinicopathological features of aggressive urothelial carcinoma of the bladder (such as stage, lymphovascular invasion and lymph node metastasis) and other molecular markers. On multivariable analyses that adjusted for standard pathological features basic fibroblast growth factor and thrombospondin 1 were independent predictors of disease recurrence (HR 3.6, p = 0.002 and HR 2.2, p = 0.001, respectively) and cancer specific mortality (HR 2.8, p = 0.02 and HR 2.3, p = 0.003, respectively). When all 4 markers were included in 1 model basic fibroblast growth factor and thrombospondin 1 retained their independent association with disease recurrence (HR 2.9, p = 0.014 and HR 1.8, p = 0.022, respectively) and only thrombospondin 1 was independently associated with cancer specific mortality (HR 1.9, p = 0.031). CONCLUSIONS: Angiogenesis related molecular markers are commonly altered in urothelial carcinoma of the bladder, making them a target for therapy. Down-regulation of thrombospondin 1 and up regulation of basic fibroblast growth factor are independent predictors of clinical outcomes of patients with urothelial carcinoma of the bladder. PMID- 20299038 TI - Active surveillance for renal cortical neoplasms. AB - PURPOSE: We retrospectively evaluated our single center experience with patients with renal cortical neoplasms who elected active surveillance. MATERIALS AND METHODS: We retrospectively evaluated our urological oncology database between January 1993 and January 2009, identifying a total of 223 renal cortical neoplasms in 212 patients that were initially managed by active surveillance. We described patient and tumor characteristics, and assessed the differences between patients who remained on AS and those who underwent delayed intervention or progressed with metastasis. RESULTS: Median patient age was 71 years at active surveillance initiation and the median Charlson comorbidity index was 3. Median tumor size was 2.8 cm (range 0.5 to 13.7) at study enrollment and 3.7 cm (range 0.9 to 14.1) at final assessment. The median growth rate in the entire cohort was 0.34 cm per year (range 0.29 to 2.3). Median followup was 35 months (range 6 to 137). Active surveillance failed in 15 patients (7%), of whom 4 (2%) progressed to metastasis and 11 (5%) required intervention. When comparing cases of failed active surveillance with those that continued, there were statistical differences in initial tumor size (2.61 vs 3.64 cm, p = 0.019), final tumor size (3.56 vs 5.17 cm, p = 0.001) and growth rate (0.34 vs 1.75, p = 0.001). There was no correlation between initial tumor size and growth rate (Pearson's coefficient r = 0.006, p = 0.932). A total of 14 patients died of another medical condition. Only 1 cancer related death (0.5%) was reported in the entire cohort. CONCLUSIONS: Active surveillance for renal cortical neoplasms in select older patients with comorbidities is a reasonable treatment option. At 3-year followup we noted a 7% failure rate. PMID- 20299039 TI - Prostate cancer screening in men 75 years old or older: an assessment of self reported health status and life expectancy. AB - PURPOSE: Opinions vary regarding the appropriate age at which to stop prostate specific antigen screening. Some groups recommend screening men with a greater than 10-year life expectancy while the United States Preventive Services Task Force recommends against screening men 75 years old or older. In this study we evaluated the influence of health status and life expectancy on prostate specific antigen screening in older men in the United States before the 2008 United States Preventive Services Task Force guidelines. MATERIALS AND METHODS: The study cohort comprised 718 men age 75 years or older without a history of prostate cancer who responded to the 2005 National Health Interview Survey, representing an estimated 4.47 million noninstitutionalized men in the United States. Life expectancy was estimated from age and self-reported health status. RESULTS: Overall 19% of the men were 85 years old or older and 27% reported fair or poor health. In the previous 2 years 52% had a prostate specific antigen screening test. After adjustment for age, race, education and physician access, men with fair or poor health were less likely to receive prostate specific antigen screening than those with excellent or very good health (adjusted OR 0.51, 95% CI 0.33-0.80, p = 0.003). Overall 42% of the men predicted to live less than 5 years and 65% of those predicted to live more than 10 years reported having recent prostate specific antigen screening. CONCLUSIONS: Before the United States Preventive Services Task Force recommendation, health status and life expectancy were used to select older men for prostate specific antigen screening. However, many men expected to live less than 5 years were screened. A strict age cutoff of 75 years reduces over screening but also prohibits screening in healthy older men with a long life expectancy who may benefit from screening. PMID- 20299040 TI - Complications after radical and partial nephrectomy as a function of age. AB - PURPOSE: Partial nephrectomy may be underused compared with radical nephrectomy in elderly patients due to concerns about higher complication rates. We determined if the association of age and perioperative outcomes differed between nephrectomy types. MATERIALS AND METHODS: We identified patients who underwent radical or partial nephrectomy between January 2000 and October 2008. Using multivariable methods we determined whether the relationship between age and risk of postoperative complications, estimated blood loss or operative time differed by nephrectomy type. RESULTS: Of 1,712 patients 651 (38%) underwent radical nephrectomy and 1,061 (62%) underwent partial nephrectomy. Patients treated with partial nephrectomy had higher complication rates than those who underwent radical nephrectomy (20% vs 14%). In a multivariable model age was significantly associated with a small increase in risk of complications (OR for 10-year age increase 1.17, 95% CI 1.04-1.32, p = 0.009). When including an interaction term between age and procedure type, the interaction term was not significant (p = 0.09), indicating there was no evidence the risk of complications associated with partial vs radical nephrectomy increased with advancing age. There was no evidence that age was significantly associated with estimated blood loss or operative time. CONCLUSIONS: We found no evidence that elderly patients experience a proportionally higher complication rate, longer operative times or higher estimated blood loss from partial nephrectomy than do younger patients. Given the advantages of renal function preservation we should expand the use of nephron sparing treatment to renal tumors in elderly patients. PMID- 20299041 TI - Robotic radical prostatectomy for elderly patients: probability of achieving continence and potency 1 year after surgery. AB - PURPOSE: We assessed the probability of achieving continence and potency after robotic radical prostatectomy in elderly patients. MATERIALS AND METHODS: The cohort included 1,436 robotic radical prostatectomy cases performed at our institution between 2003 and 2008. Continence (pad-free) and potency (erection sufficient for intercourse) at baseline and 1 year after surgery were evaluated by the UCLA-PCI questionnaire. Point estimates of the predicted probabilities of continence and potency for age 65, 70 and 75 years were calculated from multivariate logistic regression models adjusting for age, nerve sparing status, baseline International Prostate Symptom Score and baseline Sexual Health Inventory for Men score. Patients who were impotent before surgery or those who received hormones or radiation within 1 year after surgery were censored. RESULTS: Mean patient age was 60 years (range 38 to 85) with 25% older than 65 years and 77 (5%) 70 years old or older. Age (OR 0.97, p = 0.002), baseline I-PSS (OR 0.98, p = 0.02) and Sexual Health Inventory for Men scores (OR 1.02, p = 0.005) were independently associated with being pad-free. Age (OR 0.92, p <0.0001), baseline Sexual Health Inventory for Men score (OR 1.1, p <0.0001) and bilateral nerve sparing (OR 2.92, p <0.0001) were independently associated with achieving potency. Predicted probabilities (95% CI) of postoperative 1-year continence at age 65, 70 and 75 years were 0.66 (0.63, 0.69), 0.63 (0.57, 0.68) and 0.59 (0.52, 0.66), respectively. The corresponding probabilities of postoperative 1-year potency after bilateral nerve sparing were 0.66 (0.62, 0.71), 0.56 (0.49, 0.64) and 0.46 (0.36, 0.56). CONCLUSIONS: In our experience there is an acceptable probability of achieving continence and potency after robotic radical prostatectomy in selected elderly patients. PMID- 20299042 TI - Marker lesion experiments in bladder cancer--what have we learned? AB - PURPOSE: In marker lesion experiments a single bladder tumor is deliberately left unresected for later ablation by intravesical instillation of a novel agent. While the benefits are clear, eg the opportunity to examine the effect of therapy on measurable disease, the safety and medical ethics of these experiments are less obvious. We review the goals, inclusion criteria, definition of success, agents used, effectiveness, safety and ethics of marker lesion studies, and suggest a framework for future experiments. MATERIALS AND METHODS: Published bladder cancer studies using the marker lesion concept were identified with a MEDLINE search through March 2009. RESULTS: A total of 23 well documented marker lesion studies were identified involving more than 1,200 patients. Most agents studied were cytotoxins (mitomycin-C, epirubicin, gemcitabine, valrubicin, apaziquone) or immune response modifiers (bacillus Calmette-Guerin, tumor necrosis factor-alpha, interferon-alpha, granulocyte-macrophage colony stimulating factor). The highest complete response rate in intermediate risk patients (67%) was attained with apaziquone. Patients who achieved a complete response with this agent also had a prophylactic benefit with a 2-year recurrence free rate of 45.2% compared to 26.7% in those who did not achieve a complete response. The complete response rate in bacillus Calmette-Guerin trials ranged from 32% to 61%. Marker lesion experiments were deemed safe with progression to T2 disease in only 7 patients (0.6%) and only when high risk patients were selected. CONCLUSIONS: Marker lesion studies are most appropriate for the evaluation of novel anticancer therapeutics. Only patients with multiple recurrent, noninvasive, low grade tumors (intermediate risk) should be recruited. Primary end points should be complete response and recurrence rates after 2 to 3 years. PMID- 20299043 TI - Preoperative hydronephrosis predicts extravesical and node positive disease in patients undergoing cystectomy for bladder cancer. AB - PURPOSE: Preoperative hydronephrosis may be associated with a worse outcome in patients who undergo radical cystectomy for invasive bladder cancer. We characterized the prognostic significance of hydronephrosis, and its relationship to cancer stage and outcome. We also evaluated concordance between the side of identifiable hydronephrosis and concomitant pelvic lymph node metastasis. MATERIALS AND METHODS: We analyzed information from our prospectively collected database of patients who underwent radical cystectomy for bladder cancer from January 2001 to December 2007. We examined the relationship between hydronephrosis and clinical variables as well as survival outcome. Hydronephrosis was diagnosed intraoperatively or by radiographic imaging within 3 months of radical cystectomy. RESULTS: Of 753 patients 244 (32%) were diagnosed with hydronephrosis. Logistic regression modeling revealed that hydronephrosis was an independent predictor of extravesical disease (OR 2.01, 95% CI 1.37 to 2.96, p <0.001) and node positive disease (OR 1.94, 95% CI 1.29 to 2.91, p = 0.001). Of patients with hydronephrosis 88 (36.1%) had concomitant node positive disease and 74 (30.3%) had node positive disease on the same side as hydronephrosis. Thus, hydronephrosis predicted the side of nodal involvement in 74 of 88 patients (84%) with identifiable hydronephrosis and node positive disease. CONCLUSIONS: Hydronephrosis is an independent predictor of advanced bladder cancer stage, and it predicts extravesical disease and node positive disease. Thus, it could prove useful to select patients for neoadjuvant chemotherapy before surgery. The strong correlation between hydronephrosis side and nodal metastasis may have implications for surgical staging and approach. PMID- 20299044 TI - Reporting of harm in randomized controlled trials published in the urological literature. AB - PURPOSE: Evidence-based decision making seeks to balance potential benefits and harms (adverse effects) of health care interventions for an individual patient. We determined the prevalence and completeness of harm reporting in randomized controlled trials in the urological literature. MATERIALS AND METHODS: We performed a systematic literature search of all randomized controlled trials of therapeutic interventions published in The Journal of Urology, Urology, European Urology and BJU International in 1996 and 2004. Each article was reviewed by 2 independent investigators for 10 harm reporting criteria recommended by the CONSORT group. Discrepancies were settled by discussion and consensus. RESULTS: A total of 152 randomized controlled trials met the inclusion criteria, of which 109 (72%) reported adverse event outcomes. The median number of harm reporting criteria satisfied improved marginally from 1996 to 2004 (2.8 to 3.3, p = 0.36). A large proportion of studies failed to address harm in the abstract (55, 36%), introduction (71, 47%) and discussion (52, 34%). Few studies specified which adverse events were evaluated (21, 14%), when harm information was collected (32, 21%) or how the harm was attributed to the intervention (5, 3%). Only 48 (32%) articles provided reasons for patient withdrawal and 1 in 5 (33, 22%) reported the severity of adverse events. CONCLUSIONS: Randomized controlled trials published in the urological literature contain significant deficiencies in adverse event reporting. These findings suggest the need for reporting standards for harm in urological journals. Improvements in adverse event reporting would permit a more balanced assessment of interventions and would enhance evidence based urological practice. PMID- 20299045 TI - Optical coherence tomography in the kidney: a step toward echo microscopy. PMID- 20299046 TI - Editorial comment. PMID- 20299047 TI - Kidney tumor location measurement using the C index method. AB - PURPOSE: Tumor location assessment is essential to plan nephron sparing kidney surgery. We describe a method to quantify the proximity of kidney tumors to the renal central sinus for reporting and surgical management. MATERIALS AND METHODS: Centrality index scoring was done using standard 2-dimensional cross-sectional computerized tomography images in 133 consecutive patients undergoing transperitoneal laparoscopic partial nephrectomy between September 2003 and November 2005. The Pythagorean theorem was used to calculate the distance from tumor center to kidney center. The distance was divided by tumor radius to obtain the centrality index. We assessed the correlation of the centrality index with laparoscopic partial nephrectomy operative parameters and the urological complication rate. Centrality index accuracy and interobserver variability were assessed. RESULTS: A centrality index of 0 equates to a tumor that is concentric with the center of the kidney. A centrality index of 1 equates to a tumor with its periphery touching the kidney center. As the centrality index increases, the tumor periphery becomes more distant from the kidney center. Multivariate regression analysis revealed an association of the centrality index with warm ischemia time (p = 0.004), which is a surrogate for technical complexity. Interobserver correlation of centrality index values was greater than 93% with an estimated learning curve of 14 cases required for measurement variability to decrease below 10% of the mean centrality index of 10 consecutive cases. CONCLUSIONS: Centrality index scoring provides a clinically useful measure of tumor centrality. This system may allow improved clinical and radiological assessment of kidney tumors, and improved reporting of quantitative tumor site. PMID- 20299048 TI - Editorial comment. PMID- 20299049 TI - Editorial comment. PMID- 20299050 TI - The 50-year history of the ice water test in urology. AB - PURPOSE: The ice water test was first described in a 1957 study of cold receptors in the bladder. We examined the role of the ice water test in the diagnosis and management of different urological conditions. MATERIALS AND METHODS: MEDLINE and PubMed literature searches were performed, spanning 1956 to January 2009. Other studies were identified by reviewing secondary references in the original citations. RESULTS: The ice water test has been shown to be a lower motoneuron segmental reflex involving C-fiber afferents, which are associated with cold receptors. A number of its clinical applications have been described. The test was first thought to be specific to upper motoneuron lesions but patients with other urological conditions have had a positive test, including those with nonneurogenic disorders. The test is almost always negative (contractions less than 15 cm H(2)O) in healthy volunteers and in patients with stress urinary incontinence, lower motoneuron conditions and bladder pain syndrome. In cases of upper motoneuron conditions the positive test rate is 46% to 92% depending on the underlying pathological condition. CONCLUSIONS: The ice water test has several potential applications but it is not needed in routine clinical practice. To date the main interest has been in patients with neurogenic bladder disorders. Further studies to investigate the validity and reliability of the ice water test in patients with idiopathic detrusor overactivity could prove useful. PMID- 20299051 TI - Editorial comment. PMID- 20299052 TI - Impact of ischemia on renal function after laparoscopic partial nephrectomy: a multicenter study. AB - PURPOSE: We assessed the influence of renal ischemia on long-term global renal function after laparoscopic partial nephrectomy in patients with 2 functioning kidneys in a large, multicenter cohort. MATERIALS AND METHODS: Collected data included demographic, clinical and surgical characteristics, tumor parameters and renal function outcomes at 4 institutions in a total of 401 patients with 2 functioning kidneys who underwent laparoscopic partial nephrectomy. Renal function was assessed in the immediate postoperative period (days 1 to 3) and at last followup (greater than 1 month) using the estimated glomerular filtration rate calculated by the 4-variable Modification of Diet in Renal Disease equation. Ischemia time and covariates were modeled on the percent change in the estimated glomerular filtration rate using linear regression. RESULTS: Median ischemia time was 29 minutes (IQR 22, 34). The postoperative change and the last (long-term) change in the estimated glomerular filtration rate were -16% and -11%, respectively. Median time to the last estimated glomerular filtration rate measurement was 13 months (IQR 6, 24). On multivariate analysis shorter ischemia and operative times, external or ureteral irrigation with cold saline and female gender were associated with less postoperative percent change in the estimated glomerular filtration rate. Smaller tumor size and absent diabetes were associated with less of a final percent change in the estimated glomerular filtration rate. Ischemia time was not associated with a percent change in the estimated glomerular filtration rate at last followup. CONCLUSIONS: Within the range of times in these series renal ischemia did not have a clinically significant impact on global renal function in patients with 2 functioning kidneys who underwent laparoscopic partial nephrectomy, as measured by the estimated glomerular filtration rate. PMID- 20299053 TI - Editorial comment. PMID- 20299054 TI - Editorial comment. PMID- 20299055 TI - Evidence supports a faster growth rate and/or earlier transformation to clinically significant prostate cancer in black than in white American men, and influences racial progression and mortality disparity. AB - PURPOSE: The incidence of prostate cancer is approximately 60% higher and the mortality rate is 2 to 3 times greater in black than in white American men. We propose that a more rapid prostate cancer growth rate and/or earlier transformation from latent to aggressive prostate cancer in black than in white men contribute to this disparity. MATERIALS AND METHODS: We evaluated entirely embedded prostate glands on autopsy from 1,056 black and white men who died of causes other than prostate cancer. We also reviewed data from our radical prostatectomy database and from the Detroit Surveillance, Epidemiology and End Results database. RESULTS: Autopsy data indicated that subclinical prostate cancer in black and white men starts at early age and clinical characteristics do not differ by race at early ages. Radical prostatectomy specimen data revealed that prostate cancer volume and Gleason grade were greater in black than in white men. Advanced or metastatic prostate cancer occurred at a 4:1 ratio in black and white men, respectively, in the Detroit Surveillance, Epidemiology and End Results registry database. CONCLUSIONS: Results showed that age at prostate cancer initiation and clinical characteristics did not differ by race in our autopsy series, prostate cancer volume after radical prostatectomy was greater in black than in white men and disease became distant disease at a ratio of 4 black men to 1 white man in the Detroit Surveillance, Epidemiology and End Results population. These findings support the concept that prostate cancer grows more rapidly in black than in white men and/or earlier transformation from latent to aggressive prostate cancer occurs in black than in white men. PMID- 20299056 TI - Development and validation of the Bladder Cancer Index: a comprehensive, disease specific measure of health related quality of life in patients with localized bladder cancer. AB - PURPOSE: We developed and validated a reliable, responsive multidimensional instrument to measure disease specific health related quality of life in bladder cancer survivors treated with local cancer therapy. MATERIALS AND METHODS: Instrument content was based on qualitative information obtained from a panel of bladder cancer providers and from patient focus groups. Draft items were piloted and revised, resulting in the 36-item Bladder Cancer Index consisting of urinary, bowel and sexual health domains. Internal consistency, test-retest reliability, convergent validity, concurrent validity and criterion validity were then assessed. RESULTS: Internal consistency was high at 0.77 to 0.91. Test-retest reliability was also high at 0.73 to 0.95. Correlations among the 3 domains were low (r < or = 0.39), indicating interscale independence. Health outcome discrimination was apparent in clinically distinct treatment groups. Moderate correlation was observed with existing external measures, indicating that the Bladder Cancer Index detects aspects of health related quality of life related to bladder cancer treatments that are not recorded by more general measures. CONCLUSIONS: The Bladder Cancer Index is a robust, multidimensional measure of bladder cancer specific health related quality of life and to our knowledge is the first available validated instrument to assess health outcomes across a range of local treatments commonly used for bladder cancer. PMID- 20299057 TI - Repeat partial nephrectomy on the solitary kidney: surgical, functional and oncological outcomes. AB - PURPOSE: We examined outcomes in patients with recurrent or de novo renal lesions treated with repeat partial nephrectomy on a solitary kidney. MATERIALS AND METHODS: We reviewed the records of patients who underwent nephron sparing surgery at the National Cancer Institute from 1989 to 2008. Patients were included in analysis if they underwent repeat partial nephrectomy on a solitary kidney. Perioperative, functional and oncological outcomes were assessed. Functional outcomes were evaluated using the Modification of Diet in Renal Disease equation for the estimated glomerular filtration rate. Oncological efficacy was examined by the need for subsequent repeat renal surgery and the development of metastatic disease. RESULTS: A total of 25 patients were included in the analysis. A median of 4 tumors were resected. Median estimated blood loss was 2,400 ml and median operative time was 8.5 hours. Perioperative complications occurred in 52% of patients, including 1 death and the loss of 3 renal units. There was a decrease in the estimated glomerular filtration rate at followup visit 1 within 3 months after surgery but at 1-year followup the difference was not significant (p <0.01 and 0.12, respectively). Surgical intervention was recommended in 8 patients (38%) for recurrent or de novo tumors at a median of 36 months. The average metastasis-free survival rate in the cohort was 95% at 57 months (median 50, range 3 to 196). CONCLUSIONS: Repeat partial nephrectomy in patients with solitary kidney is a high risk alternative. The complication rate is high and there is a modest decrease in renal function but most patients remain free of dialysis with acceptable oncological outcomes at intermediate followup. PMID- 20299058 TI - Loss of heterozygosis on IFN-alpha locus is a prognostic indicator of bacillus Calmette-Guerin response for nonmuscle invasive bladder cancer. AB - PURPOSE: We evaluated the role of loss of heterozygosity on the interferon-alpha locus to predict the response to bacillus Calmette-Guerin therapy in patients with nonmuscle invasive bladder cancer. MATERIALS AND METHODS: A total of 117 consecutive patients were selected, including 77 with nonmuscle invasive bladder cancer and 40 controls. Loss of heterozygosity on the interferon-alpha locus (chromosome 9p21) was assessed in blood and urine samples before transurethral resection. All patients underwent transurethral resection and then 6 weekly bacillus Calmette-Guerin instillations. Those with nonmuscle invasive bladder cancer were assigned to groups 1 and 2 with and without loss of heterozygosity on the interferon-alpha locus, respectively. RESULTS: Of the 77 patients with nonmuscle invasive bladder cancer 39 (50.6%) had loss of heterozygosity on the interferon-alpha locus (group 1) and 38 (49.4%) had no alteration (group 2). Only 1 of 40 controls showed loss of heterozygosity on the interferon-alpha locus. At the end of followup 13 patients in group 1 and 27 in group 2 were alive without recurrence. We noted a significant difference between loss of heterozygosity on interferon-alpha and followup status (dF 01, LR 11.252, p = 0.003). Kaplan-Meier analysis revealed a significant difference in recurrence probability (response to bacillus Calmette-Guerin) and loss of heterozygosity on interferon-alpha (p <0.0001). On multivariate analysis loss of heterozygosity (HR 4.09, 95% CI 2.59 6.28, p = 0.002), grade (grade 3 HR 3.31, 95% CI 1.38-3.35, p = 0.03) and the number of lesions (3 or greater HR 2.31, 95% CI 1.38-3.25, p = 0.03) were independent predictors of the bacillus Calmette-Guerin response. CONCLUSIONS: This study highlights the predictive value of loss of heterozygosity analysis on interferon-alpha in patients with nonmuscle invasive bladder cancer treated with bacillus Calmette-Guerin. PMID- 20299059 TI - Characteristics and outcomes of patients with clinical carcinoma in situ only treated with radical cystectomy: an international study of 243 patients. AB - PURPOSE: We describe the rate of up staging and the cancer specific outcomes of patients with carcinoma in situ refractory to transurethral resection with intravesical therapy treated with radical cystectomy. MATERIALS AND METHODS: The records of 3,207 patients treated with radical cystectomy for urothelial carcinoma of the bladder at 8 centers in the United States, Canada and Europe were reviewed. RESULTS: Of the 3,207 patients who underwent radical cystectomy 243 (7.6%) had clinical carcinoma in situ only disease before radical cystectomy. At radical cystectomy 117 patients (48.1%) had carcinoma in situ only, 20 (8.2%) had pT0 urothelial carcinoma of the bladder, 19 (7.8%) had pTa urothelial carcinoma of the bladder and 36% had disease up staged (32 [13.2%] pT1, 29 [11.9%] pT2, 12 [4.9%] pT3 and 14 [5.8%] pT4). A total of 22 patients (9.1%) had lymphovascular invasion in the radical cystectomy specimen and 14 (5.8%) had metastasis to regional lymph nodes. Overall 5-year recurrence-free and cancer specific survival estimates were 74% (95% CI 68-79) and 85% (95% CI 80-89), respectively. On multivariable analysis adjusting for the effects of standard predictors, lymph node metastasis and lymphovascular invasion were associated with an increased risk of disease recurrence (p = 0.017 and p = 0.043, respectively) and cancer specific mortality (p = 0.019 and p = 0.001, respectively). Female gender was an independent risk factor for cancer specific mortality (p = 0.029) but not for disease recurrence (p = 0.173). CONCLUSIONS: Approximately a fourth of patients treated with radical cystectomy for clinical carcinoma in situ only had muscle invasive disease and 5.8% had metastasis to regional lymph nodes. Identification of those patients with a potentially aggressive natural history of carcinoma in situ is of the utmost importance as they are likely to benefit from early radical cystectomy. PMID- 20299060 TI - Percutaneous radio frequency ablation of renal tumors in patients with von Hippel Lindau disease: preliminary results. AB - PURPOSE: We investigated the preliminary results of percutaneous radio frequency ablation for renal tumors in patients with von Hippel-Lindau disease. MATERIALS AND METHODS: Between October 2005 and April 2009 image guided radio frequency ablation was performed to ablate a total of 48 renal tumors in 11 patients with von Hippel-Lindau disease. Six of the 11 patients had undergone radical or partial nephrectomy for renal cell carcinomas. We recorded whether tumors were successfully ablated, major complications, and changes in serum creatinine and the estimated glomerular filtration rate. RESULTS: A total of 29 sessions (70 ablations) were done. Of 48 tumors 42 (88%) were successfully ablated at 1 (41) or 3 (1) sessions and 6 (12%) had residual or recurrent lesions. Two residual tumors were treated with nephrectomy, 2 were too small to be ablated and 1 was treated with chemotherapy due to pulmonary metastasis. The remaining residual tumor was completely ablated at 2 sessions but recurred. Overall 8 of 11 patients (73%) were successfully treated with radio frequency ablation but 3 (27%) had residual or recurrent tumors. Two major complications (6.9%) developed at a total of 29 sessions, including arteriovenous fistula and ureteral perforation. Mean serum creatinine increased 11.2% and the mean estimated glomerular filtration rate decreased 9.4% after the last ablation. CONCLUSIONS: Percutaneous radio frequency ablation may be a treatment option for multifocal renal tumors in patients with von Hippel-Lindau disease but preliminary results were not satisfactory due to technical failure. PMID- 20299061 TI - Are we making significant progress in the diagnosis and management of bladder cancer? PMID- 20299062 TI - Standardization of reporting surgical complications--are we ready? PMID- 20299063 TI - Editorial comment. PMID- 20299064 TI - Do anxiety and distress increase during active surveillance for low risk prostate cancer? AB - PURPOSE: Anxiety and distress may be present in patients with low risk prostate cancer who are on active surveillance. This may be a reason to discontinue active surveillance. MATERIALS AND METHODS: A total of 150 Dutch patients with prostate cancer on active surveillance in a prospective active surveillance study received questionnaires at study inclusion and 9 months after diagnosis. We assessed changes in scores on decisional conflict with the decisional conflict scale, depression with the Center for Epidemiologic Studies Depression Scale, generic anxiety with the State Trait Anxiety Inventory, prostate cancer specific anxiety with the Memorial Anxiety Scale for Prostate Cancer and the self-estimated risk of progression. We explored scores 9 months after diagnosis vs those at study inclusion for physical health (SF-12 physical component summary), personality (Eysenck Personality Questionnaire), shared decision making, prostate cancer knowledge, demographics, medical parameters and prostate specific antigen doubling time during followup. RESULTS: Questionnaires at study inclusion and 9 months after diagnosis were completed by 129 of 150 (86%) and 108 of 120 participants (90%) a median of 2.4 and 9.2 months after diagnosis, respectively. Anxiety and distress at study inclusion were previously found to be generally favorable. Significant but clinically irrelevant decreases were seen in mean scores of the State Trait Anxiety Inventory (p = 0.016), Memorial Anxiety Scale for Prostate Cancer fear of progression subscale (p = 0.005) and the self estimated risk of progression (p = 0.049). Anxiety and distress 9 months after diagnosis were mainly predicted by scores at study inclusion. Higher Eysenck Personality Questionnaire neuroticism score and an important role of the physician in the treatment decision had additionally unfavorable effects. Good physical health, palpable disease and older age had favorable effects. No association was seen for prostate specific antigen doubling time. Nine men discontinued active surveillance, including 2 due to nonmedical reasons. CONCLUSIONS: Anxiety and distress generally remain favorably low during the first 9 months of surveillance. PMID- 20299065 TI - [Hematopoietic orbital tumors]. AB - Non Hodgkin B cell lymphomas account for most hematopoietic orbital tumors and 10 % of all orbital tumors. Typically, orbital lymphomas present as salmon-pink, painless, and slow growing conjunctival tumors affecting patients over 50 years of age. Therapeutic orientation is guided by biopsy. PMID- 20299067 TI - [Bichat's buccal fat pad for reconstruction of posterior oral cavity defects]. AB - Some losses of matter in the posterior area of the oral cavity require reconstruction with vascularized tissue to prevent retraction and a limited mouth opening. Bichat's fat pad or Bichat's fat ball is rarely used for oral mucosal reconstruction despite its proximity, easy availability, plasticity and simple use as a flap. Bichat's fat pad is resistant to lipolysis even in case of major weight-loss. It usually herniates in the exeresis site of a jugal tumor or intermaxillary commissure. When this is not the case, it can be obtained by a horizontal vestibular incision. The fat pad is unfolded and sutured without tension to the margin of the defect. The flap may be protected by a Bourdonnet dressing. Epithelialization begins 8 to 10 days after surgery. It is completed in the second or third week. The fat volume is variable, thus filling can only be applied to areas with loss of matter under 6cm. The technique is simple and quick. Postoperative evolution is usually uneventful; healing is quick as well as recovery of normal feeding function. PMID- 20299066 TI - [Orbital tumors. Neurosurgical activity]. AB - In this chapter, we report the results of orbital tumor management in a few neurosurgical departments and compare it to a Paris neurosurgical department that has developed a close relation with an ophthalmological department. These departments' activity is quite low, treating mainly sphenoorbital meningiomas. Other tumor groups are unequally and sporadically managed. PMID- 20299068 TI - [Variation of cognitive functions and glycemia during physical exercise in Ramadan fasting]. AB - INTRODUCTION: During the month of Ramadan, Muslims fast every day from dawn to sunset. Several studies have shown that Ramadan fasting affects biochemical parameters, sleep/wake cycle, behaviour and food habits. The purpose of the study was to evaluate the effect of Ramadan fasting (RF) and physical exercise on cognitive functions, blood glucose. METHODS: Eleven healthy male volunteers aged 20.45+/-1.65 years were assessed before RF (B.RF), during the 1st week (wk), 3rd wk and 1 wk B.RF, in blood sugar, work memory (WM), visual perception (VP), before exercise (B. Ex) and after exercise (A. Ex) exercise of 1000 m. RESULTS: Compared to control days (B.RF), there were no significant changes in body mass index. Physical performance declined significantly during 1st wk (p<0.001), 3th wk (p<0.013) and before (p<0.046) of RF. At the level of the glycemia, the results show a significant effect of Ramadan by increasing gradually during Ramadan but nevertheless, the values remain lower of 100mg/dl. No significant change was observed between B. Ex and A. Ex value in WM during RF. However, the WM A. Ex value increase significantly during and after RF (respectively 1st wk (p<0.013), 3rd wk (p<0.005) and before (p<0.003). The VP was significantly affected by fasting effect (F=16.84, p<0.001) and exercise effect (F=14.01, p<0.0001), and was progressively increased 15.56% in the 1st wk, 25.69%, the 3rd wk during RF, and 27.07% A.RF, but no significant change was found in errors performances of VP during and after RF. CONCLUSION: These results showed that the intermittent fasting imply differently effects on cognitive functions and physiological. PMID- 20299069 TI - Effects of cadmium, estradiol-17beta and their interaction on gonadal condition and metamorphosis of male and female African clawed frog, Xenopus laevis. AB - To assess interaction effects between cadmium (Cd, a putative xenoestrogen) and estradiol-17beta (E(2)) on sex differentiation and metamorphosis, Xenopus laevis were exposed to solvent-control (0.005% ethanol), Cd (10microgL(-1)), E(2) (1microgL(-1)), or Cd and E(2) (Cd+E(2)) in FETAX medium from fertilization to 75d postfertilization. Each treatment was applied to four aquaria, each with 30 fertilized eggs. Mortality was recorded and animals were sampled as they completed metamorphosis (Nieuwkoop and Faber stage 66). Gonadal sex of individuals (including >or= tadpoles NF stage 55 at day 75) was determined gross morphologically and used to compute sex ratios. Time course and percent completion of metamorphosis, snout-vent length (SVL), hindlimb length (HLL) and weight were analyzed for each gender separately. Survival rates did not differ among treatments. The E(2) and Cd+E(2) treatments significantly skewed sex ratios towards females; however, no sex-ratio differences were observed between the control and Cd treatments or between the E(2) and Cd+E(2) treatments. Time course of metamorphosis was generally delayed and percent completion of metamorphosis was generally reduced in males and females exposed to Cd, E(2) or their combination compared to control animals. In males, but not females, the effect of Cd+E(2) was greater than that of individual chemicals. Weight at completion of metamorphosis was reduced only in females and only by the Cd+E(2) treatment. In conclusion, although Cd at an environmentally relevant concentration did not exhibit direct or indirect feminizing effects in Xenopus tadpoles, the metal and E(2) both had similar inhibitory effects on metamorphosis that were of greater magnitude in males than females. PMID- 20299070 TI - Inoculum carrier and contaminant bioavailability affect fungal degradation performances of PAH-contaminated solid matrices from a wood preservation plant. AB - The objective of the study was to investigate the impact of chopped wheat straw (CWS), ground corn cobs (GCC) and commercial pellets (CP), as inoculum carriers, on both growth and polycyclic aromatic hydrocarbons (PAH) degradation performances of Dichomitus squalens, Pleurotus ostreatus and Coprinus comatus. A historically-contaminated soil (HCS) and creosote-treated shavings (CTS) from the Sobeslav wood preservation plant, characterized by different relative abundances of the PAH bioavailable fractions, were used to assess the contaminated matrix effect and its interaction with both carrier and fungal strain. In HCS, best results were obtained with CP-immobilized P. ostreatus, which was able to deplete benzo[a]anthracene, chrysene, benzo[b]fluoranthene (BbF), benzo[k]fluoranthene (BkF) and benzo[a]pyrene (BaP) by 69.1%, 29.7%, 39.7%, 32.8% and 85.2%, respectively. Only few high-molecular mass PAHs such as BbF, BkF and BaP were degraded beyond their respective bioavailable fractions and this effect was confined to a limited number of inoculants. In CTS, only phenanthrene degradation exceeded its respective bioavailability from 1.42 to 1.86-fold. Regardless of both inoculum carrier and fungal species, degradation was positively and significantly (P<0.001) correlated with bioavailability in fungal microcosms on HCS and CTS and such correlation was very similar in the two matrices (R(adj)(2) equal to 0.60 and 0.59, respectively). The ability of white-rot fungi to degrade certain PAHs beyond their bioavailability was experimentally proven by this study. Although CTS and HCS considerably differed in their physico-chemical properties, PAH contents and contaminant aging, the relationship between degradation and bioavailability was not significantly affected by the type of matrix. PMID- 20299071 TI - Polychlorinated dibenzo-p-dioxins and dibenzofurans in blood and breast milk samples from residents of a schistosomiasis area with Na-PCP application in China. AB - Schistosomiasis has prevailed in some areas of China for a long time. Chinese technical sodium pentachlorophenate (Na-PCP) has been used to control the spread of snail-borne schistosomiasis since the 1960s. Polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs), impurities contained in the Na-PCP, enter the soil and may accumulate in the food chain. In order to evaluate their potentially harmful effects on local residents, 50 breast milk samples and 20 blood samples were collected in 2004 from residents in the Dongting Lake area, one of China's known schistosomiasis areas. Levels of 17 PCDD/F congeners were measured in all samples, and DNA damage was simultaneously assessed in blood samples. The PCDD/F congener distribution patterns in human tissue samples from the Dongting Lake area were similar to those in Na-PCP, and the octachlorodibenzodioxin (OCDD) congener was predominant in all samples. We also had a primary investigation that the breast milk WHO-TEQ associated with some factors such as: age, dietary habit, body mass index (BMI) and the total menses times. In blood samples, the samples with higher OCDD level had higher DDS (DNA damage score) values than those samples with low OCDD level, which indicated that the higher DNA damage value in general population might be caused directly or indirectly by PCDD/Fs. The results also indicated that the WHO-TEQ values in blood were associated with age (r=0.6, p=0.007). PMID- 20299072 TI - Development of an environmental friendly method for the analysis of organochlorine pesticides in sediments. AB - This work proposes a pressurized hot water extraction (PHWE) followed by solid phase microextraction (SPME) and determination by gas chromatography-mass spectrometry method for the analysis of organochlorine pesticides in sediment samples. For SPME, extraction temperature and time, desorption temperature and desorption time, and effect of an organic modifier were studied. For PHWE, parameters such as organic modifier, percentage of organic modifier, temperature, and static extraction time were studied. When these parameters were selected, the figures of merit were calculated in order to assess the performance of the proposed method. Quantitative recoveries (80-115%) and satisfactory precisions were obtained. The detection and quantification limits were between 0.11 and 16 microg kg(-1) and between 0.24 and 22 microg kg(-1), respectively with good linearity between LOQs and 500 microg kg(-1) for most of the studied pesticides. The method was validated by the analysis of a reference marine sediment material (SRM 1944). The obtained results are in excellent agreement with the certificate material. Another sediment reference material (SRM 1941b), with a very low concentration of pesticides was also analyzed with good results. In addition, this method was successfully applied to the analysis of three marine sediment samples. The developed method seems to be a nearly full automated, environmental friendly, sensitive, simple and less-time consuming method. Moreover this method, look for the implementation of the principles of green analytical chemistry and has demonstrated to be suitable for the analysis of organochlorine pesticides at trace levels in environmental matrices as sediment samples. PMID- 20299073 TI - Concentrations and accumulation features of PCDDs, PCDFs and dioxin-like PCBs in cetaceans from Korean coastal waters. AB - Despite several studies that report accumulation of polychlorinated biphenyls (PCBs) and DDT in marine mammals worldwide, very few have examined polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) and dioxin-like PCBs. In particular, no earlier studies have reported concentrations and accumulation profiles of persistent organic pollutants (POPs) in marine mammals from Korea. In this study, concentrations and accumulation features of PCDD/Fs and dioxin-like PCBs were measured in liver and blubber of minke whales and long beaked common dolphins collected from Korean coastal waters. The concentrations of PCDFs and dioxin-like PCBs in blubber were 3-10 times higher than the concentrations measured in liver, but PCDDs were higher in liver than blubber. Total toxic equivalent (TEQ) concentrations in blubber of minke whales and common dolphins from Korean coastal waters were similar to, or higher than those reported for cetaceans and seals from other countries. Homologue and congener profiles of PCDD/Fs were different between livers and blubbers, while the profiles of dioxin-like PCBs were similar between the tissues. Concentrations of PCDD/Fs and dioxin-like PCBs in liver and blubber of dolphins were significantly higher than those measured in whales, due to differences in habitat and diet. The relative contribution of individual chemical groups to total TEQs was different between the two cetacean species, suggesting different exposures and metabolic activity. The TEQ levels in minke whales did not exceed the threshold level suggested for immunomodulation, while TEQs in all dolphin samples exceeded the suggested threshold level, implying potential adverse health effects from exposure to PCDD/Fs and PCBs. PMID- 20299074 TI - Reduction of compost phytotoxicity during the process of decomposition. AB - Hog manure from windrows composted at different operating strategies was used in a bioassay to determine phytotoxicity. Twelve windows that differed in composting strategies (i.e. turning frequency and moisture content adjustment) were built. The effects of hog manure water extracts on seed germination and primary root growth of cress (Lepidum sativum L.) was measured. The germination index (GI, a product of relative seed germination and root elongation) was related to the chemical characteristics (electrical conductivity, nitrogen compounds, C:N ratio, heavy metals and humification parameters) of the hog manure. The water extractable chemical properties of the hog manure that showed the highest negative correlation with GI were extractable Cu, extractable Zn and NH(4)(+)N, demonstrating that these chemical compounds gradually decrease during composting due to transformation to other compounds and immobilization effects. A GI>80 (an indicator of the disappearance of phytotoxicity) was reached when the concentrations of NH(4)(+)-N, extractable Cu, and extractable Zn were 2gkg(-1), 15mgkg(-1), and 15mgkg(-1), respectively. Multiple regression analysis revealed that NH(4)(+)-N was the most important factors affecting the phytotoxicity of the hog manure. Composting strategies employed affected the speed of composting, time of maturation, and disappearance of phytotoxicity. The disappearance of phytotoxicity corresponded with the time of maturation of the hog manure. If optimum composting conditions (windrows turned every 4d with weekly moisture adjustment to 60%) are met, phytotoxicity disappears within 56d. PMID- 20299075 TI - Spatial distribution of polybrominated diphenyl ethers and hexabromocyclododecanes in sediments from coastal waters of Korea. AB - Polybrominated diphenyl ethers (PBDEs) and hexabromocyclododecanes (HBCDs) were determined in surface sediments collected from 24 coastal locations in Korea. The concentrations of summation operatorPBDEs (defined as the sum of all targeted PBDE congeners except for BDE-209) and BDE-209 ranged from 0.05 to 32 ng g(-1) dry wt. and from 0.40 to 98 ng g(-1) dry wt., respectively. The PBDE congener compositions were dominated by BDE-209, which is in accordance with the consumption of decaBDE mixture in Korea. HBCD concentrations ranged from 0.39 to 59 ng g(-1) dry wt. Concentrations of PBDEs and HBCDs were found to be higher near locations with industrial complexes and harbors, associating these compounds to urbanization and industrialization. Significant positive correlations between PBDE and HBCD concentrations and organic carbon content in sediments imply the role played by organic matter in the contaminant transport and trapping in the aquatic environment. PMID- 20299076 TI - Human brain activation in response to visual stimulation with rural and urban scenery pictures: a functional magnetic resonance imaging study. AB - Human brain activation was assessed in terms of eco-friendliness while viewing still photographs depicting rural and urban surrounding environments with the use of a functional magnetic resonance imaging technique. A total of 30 subjects who had both rural and urban life experiences participated in this study. In order to explore the common and differential activation maps yielded by viewing two extreme types of scenery, random effect group analysis was performed with the use of one-sample and two-sample t-tests. Activation of the anterior cingulate gyrus, globus pallidus, putamen and head of the caudate nucleus was dominant during rural scenery viewing, whereas activation of the hippocampus, parahippocamus and amygdala was dominant during urban scenery viewing (p<0.01). These findings allow better characterization of neural activation, suggesting an inherent preference towards nature-friendly living. Such a theoretical acquisition may have an important practical impact in view of potential applications for bio-housing and the development of environmental psychology-related areas. PMID- 20299077 TI - A randomized comparison of totally tubeless and standard percutaneous nephrolithotomy in elderly patients. AB - OBJECTIVES: To evaluate the safety, effectiveness, and feasibility of totally (tubeless and stentless) tubeless percutaneous nephrolithotomy (PCNL) in elderly patients. Tubeless PCNL is performed widely in adult patients. METHODS: A total of 60 patients with renal stones were enrolled in this study. Patients were randomized to either a totally tubeless approach (group 1, 30 patients) or placement of an 18F nephrostomy tube (group 2, 30 patients). Patients were considered uncomplicated and suitable for randomization at the end of the operation if there was no significant bleeding or residual stone, and the pelvicaliceal system was intact. The incidence of complications, hospital stay, analgesic requirements, and stone-free rates were compared in 2 groups. RESULTS: The mean age of the patients at receipt of the surgical procedure was 67.7 years (range, 60-77) vs 66.5 years (range, 61-74), respectively. The mean stone size was 25.6 vs 22.3 mm and stone-free rate was 86% vs 83% for group 1 and 2, respectively (P > .05). The mean hospitalization time was 1.5 and 3.2 days (P < .001), the mean analgesia requirement (pethidine HCl) was 0.5 and 1.4 mg/kg, respectively (P < .01). Decrease in hematocrit was similar in 2 groups. No blood transfusions were needed. CONCLUSIONS: Totally tubeless PCNL is safe and effective procedure even in elderly patients with renal stones. The hospitalization and analgesic requirements are less than standard PCNL. However, the tubeless decision should be taken intraoperatively in selected patients. PMID- 20299078 TI - Risk of infection after midurethral synthetic sling surgery: are postoperative antibiotics necessary? AB - OBJECTIVES: To review our postoperative infections using single-dose preoperative antibiotics. Midurethral synthetic sling surgery is commonly performed. Postoperative antibiotics are often prescribed and may have some risk of adverse events (AEs). We are unaware of data suggesting decreased risk of infection with this practice. METHODS: We reviewed all midurethral synthetic sling surgery charts from 2004 to 2008 performed by 1 surgeon who uses only single-dose preoperative antibiotics (controls), and 2 who also use postoperative antibiotics(cases). A telephone survey was administered, which included questions regarding postoperative infections and AEs related to antibiotic use. Our primary and secondary outcomes were urinary tract infections (UTIs) and AEs related to antibiotic use, respectively. Patients were excluded for bladder injuries, postoperative catheters, and concomitant prolapse surgery. RESULTS: We identified 103 cases and 116 controls, and the telephone survey response rate was 81.3%. At baseline, groups had similar characteristics. There was no significant difference in UTIs between cases (6.8%) and controls (9.5%). There were no skin infections. AEs related to antibiotic use were more common among those that received postoperative antibiotics (7.8% vs 0.9%, P=.03). There were 5 (63%) yeast infections, 1 (12.5%) rash, 1 (12.5%) case of nausea, and 1 (12.5%) patient with colitis among cases and 1 yeast infection among controls. CONCLUSIONS: UTI is common after sling surgery, but other infections are rare. The occurrence of UTI does not appear to be lower when postoperative antibiotics are prescribed. However, AEs associated with antibiotic use are increased. These findings do not support the use of postoperative antibiotics. PMID- 20299079 TI - The total number of retroperitoneal lymph nodes resected impacts clinical outcome after chemotherapy for metastatic testicular cancer. AB - OBJECTIVES: To evaluate the prognostic significance of the total number of lymph nodes obtained at postchemotherapy retroperitoneal lymph node dissection (PC RPLND). After the multidisciplinary management of metastatic germ cell tumor, approximately 10%-15% of patients with the histologic finding of fibrosis or teratoma will suffer disease recurrence. METHODS: Between 1989 and 2006, a total of 628 patients underwent PC-RPLND and were found to have either fibrosis or teratoma. After Institutional Review Board approval, complete clinical and pathologic data were obtained from our prospective testis cancer surgical database. A Cox proportional hazards regression model was constructed to evaluate the association of the total number of lymph nodes obtained at PC-RPLND on disease recurrence. RESULTS: On pathologic evaluation, 248 (57%) patients had fibrosis and 184 (43%) patients had teratoma. The median number of lymph nodes resected was 25 (interquartile range, 15-37). On multivariable analysis, increasing postchemotherapy nodal size and decreasing lymph node counts were significant predictors of disease recurrence (P=.01, .04, respectively). For patients with 10 nodes removed, the predicted 2-year relapse free probability was 90%, compared with 97% when 50 nodes were removed. CONCLUSIONS: Our data suggest that the total number of lymph nodes removed and analyzed is an independent predictor of disease recurrence after PC-RPLND. This has implications both for the urologist to assure completeness of resection and for the pathologist to meticulously assess the pathologic specimens. PMID- 20299080 TI - Clinical features and treatment options for Chinese patients with severe primary erectile dysfunction. AB - OBJECTIVES: To investigate clinical features of Chinese patients with severe primary erectile dysfunction (S-PED) and to identify the ideal treatment options for this population. METHODS: Patients with PED were screened for enrollment in our study. Sexual history, marital status, and erectile function were evaluated by inquiry including International Index of Erectile Function-5. Individuals with severe PED (defined as refractory to management with phosphodiesterase type 5 inhibitor [PDE5i]) underwent serum hormone analysis, penile color duplex Doppler ultrasound, neuroelectromyogram, and cavernosography as appropriate. Long-term treatment results were determined. RESULTS: Among 220 PED patients, 72 (32.7%) suffered from severe PED (PDE5i nonresponse). Mean age was 31.5 +/- 4.5 years and mean duration of attempts at sexual activity was 2.4 +/- 3.2 years, Sixty-eight men (94.5%) had organic etiologies for erectile dysfunction, including arteriogenic (n = 13), venogenic (n = 35), endocrinologic (n = 6), neurologic (n = 9), and cavernosal fibrosis (n = 5). Sixteen men (22.2%) had been divorced. Mean erectile function and quality-of-life were significantly improved (P <.001) in the 25 men (34.7%) who were treated by penile prosthesis implantation, at a mean follow-up of 5.6 years. Satisfaction with penile prosthesis for patients and partner was 93.4% and 92.3%, respectively. CONCLUSIONS: Severe PED has a major impact on young couple's life quality. Venous leak is the most common cause of severe PED. Penile prosthesis implantation is safe and effective for severe PED. PMID- 20299081 TI - Face validation of a novel robotic surgical simulator. AB - OBJECTIVES: To assess the face validity of Robotic Surgery Simulator (RoSS), a novel virtual reality training platform for the da Vinci Surgical System (DVSS). METHODS: Urologic surgeons, fellows, and residents attending the 2009 American Urologic Association Annual Meeting in April 2009 were invited to an orientation session with RoSS. Participants completed a questionnaire after orientation and two modules. RESULTS: Thirty participants including 24 surgeons and fellows experienced with robotic surgery and 6 robotic surgery novices participated in the study. Eighty percent participants had at least 4 years of experience with robotic surgery and 77% had performed an average of 340 cases on the DVSS as primary console surgeons. Subjects indicated that RoSS was realistically close to the DVSS console in terms of virtual simulation and instrumentation. Fifty-two percent of subjects rated RoSS somewhat close and 45% rated RoSS very close to the DVSS console. Thirty-seven percent rated RoSS pinch device somewhat close, and 47% very close to the DVSS. With regard to movement of the arms, 43% rated it somewhat close, 40% rated it very close, and 7% felt that it was just like the DVSS. Camera movement and clutch functions were rated not close (11%), somewhat close (57%), and very close (32%) to the DVSS. Data were further analyzed in terms of surgical volume. Thirty-eight percent of subjects had also tried the Mimic dV-Trainer robotic surgery simulator. CONCLUSIONS: RoSS provides opportunity for robot-assisted surgical training for future error-free surgery. Further validation will be necessary to assess RoSS and the application of specific modules for robot-assisted surgical training. PMID- 20299082 TI - Determining failure after renal ablative therapy for renal cell carcinoma: false negative and false-positive imaging findings. PMID- 20299084 TI - SIU Scholarship: Dr. Abimbola Olaniyi Olajide. PMID- 20299083 TI - Cut-off value of testes volume in young adults and correlation among testes volume, body mass index, hormonal level, and seminal profiles. AB - OBJECTIVES: To set a population-based cut-off value of normal adult and to determine correlations of testicular volume with body mass index (BMI), seminal profiles, and hormone levels. Testicular volume is an index of male fertility but cut-off values of normal adult has not been reported. METHODS: During 54 months from January 2004, 1139 normal young men, 19-27 years old in military service were enrolled. Testicular volumes were measured by ultrasonometry. Height, body weight, and BMI were measured and semen analysis and hormone assay (follicle stimulating hormone [FSH], luteinizing hormone [LH], and testosterone) were performed. RESULTS: The mean age was 23.52+/-2.74. The mean testicular volume was 18.37+/-3.62 cm3 in left, and 18.13+/-3.85 cm3 in right. The mean body weight was 67.4+/-7.91 kg, the mean height was 176.2+/-6.64 cm, and mean BMI was 22.49+/ 2.02 kg/m2. Testicular volumes had significant but weak correlations with height, body weight, and BMI. The semen analyses showed a mean pH of 7.63+/-0.74, volume of 2.49+/-1.12 mL, count of 68.63+/-13.62x10(6), motility of 69.93%+/-10.28%, and morphology of 68.62%+/-7.48%. Sperm counts and motility had positive correlations with testicular volume. The mean hormonal levels of FSH, LH, and testosterone were 7.31+/-2.42 mIU/mL, 7.81+/-2.49 mIU/mL, and 6.23+/-1.69 ng/mL, respectively. Testicular volume was negatively correlated with FSH and LH and positively with testosterone. CONCLUSIONS: In this population-based study, we conclude that the cut-off testicular volume in normal young adults is around 18 mL and that testicular volume is positively correlated with height, body weight, BMI, semen profile, and testosterone, and negatively correlated with FSH and LH. PMID- 20299085 TI - SIU Scholarship: Dr. Mathew K. Y. Kyei. PMID- 20299086 TI - Novel cost-effective specimen retrieval bag in laparoscopy: Nadiad bag. AB - OBJECTIVES: To describe an innovative bag for effective specimen retrieval with the aim of reducing the cost of surgery. Retrieval bags are useful in specimen retrieval after ablative surgery. METHODS: The components of the retrieval bag are a polyethylene roll, nylon thread, and a 5 ureteral catheter. The lower end is double-sewn with an autoseal device. The neck of the bag consists of a folded edge of the polyethylene bag, which is single-sewn. The folded tunnel accommodates the 5F ureteral catheter and nylon thread. Introduction is performed through the 10-mm port with the help of an atraumatic grasper without any special introducer sheath. Two laparoscopic instruments are required to open, place the specimen within, and close the bag. The bag is extracted by extending the port incision, if required. RESULTS: The bag was used in 40 cases, including radical prostatectomy in 7, simple nephrectomy in 18, nephroureterectomy in 11, and adrenalectomy in 4. The running cost of the retrieval bag was or=14.5ng/g lipid adjusted had an odds ratios of 1.90 (95% CI 1.09 3.32) compared to oxychlordane <14.5ng/g lipid adjusted, and heptachlor epoxide >or=14.6ng/g lipid adjusted had an odds ratio of 1.70 (95% CI 1.16-2.49) compared to heptachlor epoxide <14.6ng/g lipid adjusted. Heptachlor epoxide and p,p'-DDT were significantly associated with pre-diabetes in separate adjusted logistic regressions. When these 2 compounds were tested together only heptachlor epoxide remained significantly associated with pre-diabetes. The evidence supporting the relationship between pesticides and pesticide metabolites, with diabetes, was strongest for heptachlor epoxide and oxychlordane, intermediate for p,p'-DDT, and least for beta-hexachlorocyclohexane, p,p'-DDE, and trans-nonachlor. Mirex and dieldrin were not associated with total diabetes or pre-diabetes. PMID- 20299100 TI - Circular Dichroism reveals evidence of coupling between immunoglobulin constant and variable region secondary structure. AB - Antibodies (Ab) are bifunctional molecules with two domains, a constant region (C) that confers effector properties and a variable (V) region responsible of antigen (Ag) binding. Historically the C and V regions were considered to be functionally independent, with Ag specificity being solely determined by the V region. However, recent studies suggest that the C region can affect Ab fine specificity. This has led to the proposal that the C(H) domain influences the structure of the V region, thus affecting Ab affinity and fine specificity. An inference from this proposal is that V region identical monoclonal Abs (mAbs) differing in C region (eg isotype) would manifest different secondary structures arising from isotype-induced variation in the V-C regions after Ag binding. We hypothesized that such effects could translate into differences in Circular Dichroism (CD) upon Ag-Ab complexes formation. Consequently we studied the interaction of a set of V region identical IgG(1), IgG(2a), IgG(2b) and IgG(3) mAbs with glucuronoxylomannan (GXM). The native CD spectra of the pairs IgG(1)/IgG(2a) and IgG(3)/IgG(2b) were strikingly similar, implying similar secondary structure content. GXM binding by IgG(1), IgG(2a), IgG(2b) and IgG(3) produced different CD changes, with the pairs IgG(1)/IgG(2a) and IgG(3)/IgG(2b) again manifesting qualitatively similar trends in secondary structure changes. The magnitude of the changes differed among the isotypes with IgG(2a)>IgG(3)>IgG(2b)>IgG(1). These differences in CD changes were interpreted to reflect differences in V-C secondary structures. PMID- 20299101 TI - Hybrid IgG4/IgG4 Fc antibodies form upon 'Fab-arm' exchange as demonstrated by SDS-PAGE or size-exclusion chromatography. AB - Human IgG4 antibodies are dynamic molecules that in vivo exchange half-molecules to become bispecific antibodies. Here we show that IgG4 antibodies and IgG4 Fc fragments similarly exchange resulting in hybrid antibodies (a single Fab+Fc) with a molecular weight of ca. 100kDa. These antibodies can be separated from IgG4 and IgG4 Fc using size-exclusion chromatography and non-reducing SDS-PAGE. This method does not rely on a cross-linking immunoassay with its potential for false-positive results due to aggregation and it unambiguously demonstrates that the 'Fab-arm' exchange process depends entirely on the Fc part (hinge+CH2+CH3). PMID- 20299102 TI - Transcription factors PU.1 and IRF4 regulate activation induced cytidine deaminase in chicken B cells. AB - The chicken immunoglobulin (Ig) variable region is preceded by multiple pseudo genes. During B cell maturation, the Ig variable region is converted into various pseudo gene sequences, and the diversity of antigen binding site is expanded as a consequence. Ig gene conversion is initiated by a B cell-specific enzyme, activation induced cytidine deaminase (AID). The mechanisms that regulate AID expression and function during Ig gene conversion in chicken B cells are not fully elucidated. In this report, we show that the transcription factor PU.1 and its functional partner, IRF4, are involved in the expression of AID gene in chicken B cells, and the regulation may be mediated in part through a composite PU.1/IRF4 binding site near the AID promoter. Relative to IRF4, PU.1 appears to be more important for AID expression, implying additional IRF4 independent roles for PU.1. Besides regulating AID expression, PU.1 and IRF4 also bind to two composite PU.1/IRF4 binding sites in the Iglambda locus, and mutations in these binding sites reduce AID-mediated gene conversion. Moreover, AID-mediated gene conversion is impaired in IRF4 deficient cells, and the defect may be a consequence of both reduced AID expression and lack of IRF4 interaction at the Iglambda locus. Based on these observations, we propose that PU.1 and IRF4 regulate AID at two levels in chicken B cells: the expression of AID as well as its gene conversion function at the Iglambda locus. PMID- 20299103 TI - Scavenger receptor CD163, a Jack-of-all-trades and potential target for cell directed therapy. AB - Scavenger receptor CD163 contains nine scavenger receptor cysteine-rich (SRCR) domains and because of the presence of this ancient and highly conserved protein motif, CD163 belongs to the SRCR superfamily. Expression of CD163 is restricted to cells of the monocyte/macrophage lineage and is tightly regulated, with a general tendency of anti-inflammatory signals to induce CD163 synthesis, while pro-inflammatory signals rather seem to downregulate CD163 expression. The first identified and most-studied function of CD163 is related to its capacity to bind and internalize haemoglobin-haptoglobin (HbHp) complexes. Later on, its functional repertoire was expanded, with the identification of CD163 as an erythroblast adhesion receptor, a receptor for tumour necrosis factor-like weak inducer of apoptosis (TWEAK), as well as a receptor for distinct pathogens encompassing bacteria and viruses. Interaction of one of these ligands with CD163 might result in receptor-mediated endocytosis, but might as well trigger a signalling cascade leading to the secretion of signalling molecules, which implicates that CD163 also acts as an immunomodulator. Not only the membrane bound form of CD163 has an immunomodulating capacity, but also soluble CD163, which is generated via ectodomain shedding, is able to exert anti-inflammatory effects. Furthermore, the concentration of this soluble protein is significantly increased under specific pathological conditions, making it a useful marker protein for certain diseases. Finally, its restricted expression pattern and potential to internalize make CD163 an attractive candidate as gateway for cell directed (immuno)therapy. This review aims to summarize current knowledge on CD163's biology and its different biological functions beyond HbHp scavenging, thereby mainly focussing on the more recently discovered ones. Furthermore, current data supporting the capacity of CD163 to serve as a diagnostic marker in certain diseases and its potential as a target molecule for cell-directed therapy are surveyed. PMID- 20299104 TI - Identification of the amino acid residues involved in human IgG transport into egg yolks of Japanese quail (Coturnix japonica). AB - In avian species, maternal immunoglobulin (Ig) Y is selectively incorporated into the yolks of maturing oocytes, although the relevance of receptor-mediated uptake is unclear. When administered to birds, several mammalian Igs, including human IgG (hIgG), are also incorporated into the yolks. In the current study, to gain insight into selective Ig transport into yolks, we intended to identify the amino acid residues critical for Ig uptake into egg yolks using alanine and glycine scanning mutagenesis of 16 residues located along the C(H)2 and C(H)3 domains of hIgG1. Wild-type hIgG1-Fc (WT) and its mutants were synthesized, and their uptakes into the egg yolks of Japanese quail (Coturnix japonica) were determined. The triple mutation of loop MIS252-254 to GGG resulted in a 40% decrease in Fc uptake in comparison to that of the WT. Furthermore, quartet substitution of HEAL429-432 to GGGG located in an exposed loop at the C(H)3 domain completely abolished Fc uptake into egg yolks. Next, the residues HEAL429-432 were individually substituted with either alanine or glycine. Regardless of the glycine and alanine substitution, single mutations of H (429), E (430) and L (432) significantly reduced Fc uptake compared with WT uptake. Notably, the blood clearance rates of these mutants were equivalent to that of the WT. These results suggest that the clustered residues HEAL429-432 in the C(H)3 domain are important for the hIgG1 transport into the egg yolks. The sequence HEAL is conserved in chicken IgY at positions 550-553 within the C(H)4 domain, which might be involved in its uptake into the egg yolks by receptor-mediated endocytosis. PMID- 20299106 TI - Cholesterol and CSF 5-HIAA in attempted suicide. AB - BACKGROUND: Low serum cholesterol has been linked to suicide and violent behaviour. The same kind of associations has been reported regarding low levels of 5-hydroxyindolacetic acid (5-HIAA) in the cerebrospinal fluid (CSF) and suicidal behaviour. The hypothesis of the link between serum cholesterol and suicide incorporate serotonin. It proposes that low cholesterol is related to altered serotonergic neurotransmission. A correlation between CSF 5-HIAA and serum cholesterol has been shown in animal studies, but has not been found in humans. AIM: To study the interrelationship between serum cholesterol and CSF 5 HIAA in suicide attempters. Since both cholesterol and CSF 5-HIAA are associated with suicide and violent suicide attempts, we also investigated the correlation with suicide, violent suicide attempt method, suicide intent, hopelessness and depression severity. METHODS: Serum total cholesterol and CSF 5-HIAA were measured in 42 medication free suicide attempters. Patients were assessed with Becks's Hopelessness scale (BHS), Suicide Intent Scale (SIS) and Montgomery Asberg depression rating scale (MADRS) and followed-up for causes of death. RESULTS: Serum total cholesterol and CSF 5-HIAA showed a significant positive correlation adjusted for age, body mass index and substance abuse diagnosis. Cholesterol and CSF 5-HIAA levels did not differ between violent and non-violent suicide attempters or between suicide completers and survivors. CONCLUSIONS: These findings indicate that the serotonergic system may be connected to serum cholesterol in patients with a recent suicide attempt. PMID- 20299107 TI - The educational patterning of health-related adversities in individuals with major depression. AB - BACKGROUND: Major depressive disorder and depression severity are socially patterned, disfavouring individuals from lower socioeconomic groups. Depressive disorders are associated with several adverse health-related outcomes. We examined the educational patterning of somatic health, lifestyles, psychological function and treatment modalities in individuals suffering from major depressive disorder. METHODS: We used cross-sectional medical and psychiatric data from 992 participants of The Netherlands Study of Depression and Anxiety (NESDA) with a diagnosed current major depressive disorder. Associations of education with somatic, lifestyle-related, and psychological outcomes, and with treatment modalities, adjusted for depression severity, were examined by means of (multinomial and binary) logistic and linear regression analyses. RESULTS: In addition to and independent of major depressions being more severe in the less educated patients, metabolic syndrome, current smoking, low alcohol consumption, hopelessness and low control were more prevalent in a group of less educated individuals suffering from major depression, compared with their more highly educated peers. The less educated persons were more likely to be treated with antidepressant medication and less likely to receive psychotherapy treatment. None of these observations were explained by a higher depression severity in the less educated group. LIMITATIONS: The cross-sectional design does not allow us to make direct causal inferences regarding the mutual influences of the different health-related outcomes. CONCLUSIONS: Further research should explore the necessity and feasibility of routine screening for additional health risk, particularly among less educated depressed individuals. PMID- 20299108 TI - Long-term follow-up of patients with obsessive-compulsive disorder treated by anterior capsulotomy: a neuropsychological study. AB - BACKGROUND: For treatment-refractory Obsessive-Compulsive-Disorder (OCD) patients, anterior capsulotomy is a potential therapy. We investigated what kinds of cognitive deficits treatment-refractory patients have and how anterior capsulotomy modifies their clinical and cognitive profiles. METHODS: Ten treatment-refractory OCD patients were examined in two groups (operated and non operated) with 5 participants in each group, matched for symptom severity, gender, age and education. The operated group was treated with anterior capsulotomy; the non-operated group was treated only with pharmaco- and psychotherapy. The Yale-Brown Obsessive-Compulsive Rating Scale (Y-BOCS) was used to measure OCD symptoms, and ten neuropsychological tests were used to measure cognitive functioning. RESULTS: In the operated group, the score of Y-BOCS score significantly decreased during the two-year follow-up period. Additionally, we found a significant increase in neuropsychological test scores on the Wechsler Intelligence Test (MAWI), California Sorting Test Part A (CST-A), Stroop Test Interference Score (STR-I), Verbal Fluency Test and Iowa Gambling Test. As a negative result, we observed intrusion errors in the Category Fluency Test. In the non-operated group significant improvement was found in Y-BOCS scores. At follow-up, we found significant differences between the operated and non-operated groups on three neuropsychological tests: Trail Making Test Part B, Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) Attention Index and RBANS Language Index, with better performance in the non-operated group. CONCLUSIONS: Both treatment methods (i.e. anterior capsulotomy and pharmaco- and psychotherapy) seem effective in reducing OCD symptoms and cognitive deficits, but, importantly, to different degrees. The clinical and neuropsychological improvements were more impressive in the operated group. PMID- 20299109 TI - Glycoprotein and carbohydrate binding protein expression in the placenta in early pregnancy loss. AB - Glycoproteins expressed at the fetal-maternal interface have been shown to exert immunomodulating effects. Glycodelin, hCG and transferrin have been used in in vitro experiments as ligands to block E-selectin-mediated cell adhesion. We found that glycodelin is a strong inhibitor of the E-selectin-mediated cell adhesion with a 10(3)-fold increase in potency compared to the monovalent tetrasaccharide sialyl Lewis X. HCG with distinct carbohydrate expression is also an effective selectin antagonist, whereas the potency of transferrin is low. This could indicate a possible role of glycodelin, hCG and transferrin in preventing leukocyte adhesion to the fetal trophoblast. In decidual tissue of abortion patients, glycodelin expression was significantly reduced compared to normal gestation. These results were confirmed by in situ hybridization. Moreover, glycodelin expression in endometrial cells in vitro could be stimulated by addition of hCG. Because hCG is down-regulated in women with abortion, we speculate that hCG could be one of the factors regulating glycodelin expression. Galectins are structurally related proteins with the ability to bind beta galactosides through a conserved carbohydrate recognition domain. Galectin-1 (gal 1) expression in the syncytiotrophoblast is down-regulated in early pregnancy loss. Gal-1 recognizes the Thomsen-Friedenreich disaccharide (Galbeta1-3GalNAc-) on the syncytiotrophoblast and extravillous trophoblast. Gal-1 also inhibited trophoblast cell proliferation but did not induce apoptosis in BeWo cells. Ligation of Gal-1 on trophoblast cells may have regulatory effects on trophoblast cell differentiation. Decreased expression of Gal-1 may partly explain disturbed trophoblast differentiation during early placentation leading to early pregnancy loss. PMID- 20299110 TI - Differential distribution of WC1(+) gammadelta TCR(+) T lymphocyte subsets within lymphoid tissues of the head and respiratory tract and effects of intranasal M. bovis BCG vaccination. AB - BCG vaccination of neonatal calves induces significant protection against bovine tuberculosis. The enhanced protection observed in neonatal calves may be linked to an enhanced capacity for IFNgamma production by innate cells, including WC1(+) gammadelta T cells, which constitute a major population in young cattle. Intranasal BCG vaccination of mice induces high levels of IFNgamma in the lungs, which may enhance protection against subsequent challenge with virulent strains of mycobacteria. We used an intranasal BCG vaccination model in calves to study the effect on the distribution of WC1(+) gammadelta T cells expressing two alternate forms of WC1: WC1.1 and WC1.2. These subsets of WC1(+) gammadelta T cells have previously been shown to have a differential capacity for IFNgamma secretion. Our results indicate that there is a selective expansion/recruitment of gammadelta T cells expressing the IFNgamma-associated WC1.1 isoform in tissues of the lungs and upper respiratory tract following intranasal BCG vaccination. PMID- 20299111 TI - Otolaryngological manifestations of 'Muckle-Wells syndrome'. AB - We present a follow-up of a cohort of three cases of Muckle-Wells syndrome (MWS). The aim of this report is to characterise the symptoms of this rare autosomal dominant condition with respect to the ENT practice. A retrospective analysis of the clinical features of MWS from our outpatient follow-up record of the three patients diagnosed with MWS. An extensive literature search was performed, using Medline through Pub Med (1950-2010), EMBASE (1980-2009) and Ovid (1958-2009). Retrospective case note study. In the present cohort, progressive sensorineural hearing loss was the main presentation and has been followed up over 10 years (median). The spectrum of head and neck presentation from the world literature was reviewed and includes hypothyroidism, amyloid goitre, cervical lymphadenopathy, and facial rash. This is the first documented report of the Otolaryngological features of the MWS in the English ENT literature. An awareness of this rare syndrome is essential in order to diagnose this uncommon syndrome and thus to plan for a long-term follow-up. PMID- 20299112 TI - Clinical correlates of age of onset in psychotic depression. AB - The issue whether the clinical characteristics of unipolar psychotic major depression (PMD) vary according to the age of onset remains still unclear. Thus, the aim of this study was to assess comparatively a broad set of clinical characteristics of three groups of PMD patients, namely young early-onset (n=30), elderly early-onset (n=34) and elderly late-onset (n=35). Ninety-nine inpatients suffering from DSM-IV unipolar PMD were assessed on the basis of Structured Clinical Interview for DSM-IV (SCID-IV), Hamilton Rating Scale for Depression (HRSD) and a physical impairment rating scale. The elderly late-onset patients suffered from overall more severe depression compared to both early-onset ones, more psychic anxiety compared to elderly early-onset patients and more gastrointestinal symptoms compared to young early-onset patients. Additionally, they expressed significantly more frequently delusions of somatic content and higher scores on the HRSD item of hypochondriasis than their young early-onset counterparts. The group of elderly early-onset PMD patients was found to hold an intermediate position between the young early-onset and elderly late-onset PMD patients with regard to hypochondriacal ideation, gastrointestinal symptoms and delusions of somatic, guilt, and paranoid content. Their stability of delusional content across successive episodes was found to extend into old age. Nevertheless, they expressed additional somatic delusions. Overall, the findings of the present study suggest considerable differences between young early-onset, elderly early-onset and elderly late-onset PMD patients with respect to their clinical features. PMID- 20299113 TI - Visualization of coronary arteries and coronary stents by low dose 320-slice multi-detector computed tomography in a patient with atrial fibrillation. AB - Cardiac multi-detector computed tomography (MDCT) is widely used in the diagnosis of coronary disease. However, the predictive value of this technique is limited in the presence of atrial fibrillation and coronary stents. Here we present a case showing the ability of the new 320-slice MDCT to assess coronary anatomy in a patient with atrial fibrillation and coronary stents. PMID- 20299114 TI - Development and validation of a bleeding risk model for patients undergoing elective percutaneous coronary intervention. AB - BACKGROUND: Accurate estimation of bleeding risk in patients undergoing elective percutaneous coronary intervention (PCI) is difficult and not based on widely accepted scores or characteristics. We developed and validated a simple prediction model for major bleeding using the SafeTy and Efficacy of Enoxaparin in PCI patients, an internationaL randomized Evaluation (STEEPLE) trial, which demonstrated the superior safety of enoxaparin over unfractionated heparin (UFH) in 3528 patients undergoing elective PCI. METHODS AND RESULTS: Independent predictors of non-coronary artery bypass graft (CABG)-related major bleeding events were determined using stepwise multivariate logistic regression analysis from a development dataset using bootstrap resampling. These predictors were assigned an integer coefficient (risk score) proportional to the estimated coefficient from the logistic model. Risk scores were tested in a validation cohort. Female sex, use of unfractionated heparin (vs. enoxaparin), and use of a glycoprotein IIb/IIIa inhibitor (vs. nonuse) were the strongest independent predictors of bleeding. Extensive testing found that the final model performed well with bootstrap resampling in the development set (c-statistic 0.75; 95% CI: 0.70-0.82; Hosmer-Lemeshow p = 0.29), validation set (c-statistic 0.67; Hosmer Lemeshow p = 0.12), and subgroups of high-risk patients analysed from the validation set (c-statistic >= 0.67). CONCLUSIONS: Our model for evaluating the risk of non-CABG-related major bleeding in patients undergoing elective PCI identified sex, the type of antithrombin used, and glycoprotein IIb/IIIa inhibitor use as important indicators of bleeding risk, and accurately predicted the incidence of non-CABG-related major bleeding in patients undergoing elective PCI in the STEEPLE trial. PMID- 20299115 TI - Effects of acute autonomic modulation on atrial conduction delay and local electrograms duration in paroxysmal atrial fibrillation. AB - Slowed atrial conduction may contribute to reentry circuits and vulnerability for atrial fibrillation (AF). The autonomic nervous system (ANS) has modulating effects on electrophysiological properties. However, complex interactions of the ANS with the arrhythmogenic substrate make it difficult to understand the mechanisms underlying induction and maintenance of AF. AIM: To determine the effect of acute ANS modulation in atrial activation times in patients (P) with paroxysmal AF (PAF). METHODS AND RESULTS: 16P (9 men; 59+/-14years) with PAF, who underwent electrophysiological study before AF ablation, and 15P (7 men; 58+/ 11years) with atrioventricular nodal reentry tachycardia, without documentation or induction of AF (control group). Each group included 7P with arterial hypertension but without underlying structural heart disease. The study was performed while off drugs. Multipolar catheters were placed at the high right atrium (HRA), right atrial appendage (RAA), coronary sinus (CS) and His bundle area (His). At baseline and with HRA pacing (600ms, shortest propagated S2) we measured: i) intra-atrial conduction time (IACT, between RAA and atrial deflection in the distal His), ii) inter-atrial conduction time (interACT, between RAA and distal CS), iii) left atrial activation time (LAAT, between atrial deflection in the distal His and distal CS), iv) bipolar electrogram duration at four atrial sites (RAA, His, proximal and distal CS). In the PAF group, measurements were also determined during handgrip and carotid sinus massage (CSM), and after pharmacological blockade of the ANS (ANSB). AF was induced by HRA programmed stimulation in 56% (self-limited - 6; sustained - 3), 68.8% (self-limited - 6; sustained - 5), and 50% (self-limited - 5; sustained - 3) of the P, in basal, during ANS maneuvers, and after ANSB, respectively (p=NS). IACT, interACT and LAAT significantly lengthened during HRA pacing in both groups (600ms, S2). P with PAF have longer IACT (p<0.05), a higher increase in both IACT, interACT (p<0.01) and electrograms duration (p<0.05) with S2, and more fragmented activity, compared with the control group. Atrial conduction times and electrograms duration were not significantly changed during ANS stimulation. Nevertheless, ANS maneuvers increased heterogeneity of the local electrograms duration. Also, P with sustained AF showed longer interACT and LAAT during CSM. CONCLUSION: Atrial conduction times, electrograms duration and fractionated activity are increased in PAF, suggesting a role for conduction delays in the arrhythmogenic substrate. Acute vagal stimulation is associated with prolonged interACT and LAAT in P with inducible sustained AF and ANS modulation may influence the heterogeneity of atrial electrograms duration. PMID- 20299116 TI - Quality of coronary arterial 320-slice computed tomography images in subjects with chronic atrial fibrillation compared with normal sinus rhythm. AB - PURPOSE: To evaluate coronary arterial image quality on 320-slice CT in subjects with chronic atrial fibrillation (CAf) vs. normal sinus rhythm (NSR). MATERIALS AND METHODS: In 92 consecutive subjects, 46 each with CAf (male:female ratio 2.54:1.00, age 69.7 +/- 9.9 years) and NSR (male:female ratio 1.88:1.00, age 63.7 +/- 13.7 years), 320-slice CT (Aquilion-one) was performed with enhanced images reconstructed at 80% of ECG R-to-R intervals. Visualized coronary vessels >1.5mm diameter in the right coronary artery, left anterior descending (LAD), and circumflex (LCx) distribution were evaluated for length, percentage of length free from motion artifacts, and image quality on a scale ranging from 1 (highest quality) to 5 (lowest quality). RESULTS: LCx length measurements were significantly greater in subjects with NSR (108.8 +/- 27.0mm) than CAf (96.6 +/- 31.4mm) (P = 0.049), whereas percentages of length free from motion artifacts did not differ between the three vascular beds. Image quality, was significantly but marginally better overall in NSR than in CAF, as well as for LAD and LCx vascular beds. Mean scores in subjects with CAf and NSR were 1.4 +/- 0.7 and 1.3 +/- 0.6 in all arteries, 1.4 +/- 0.7 and 1.2 +/- 0.5 in LAD, and 1.5 +/- 0.7 and 1.2 +/- 0.5 in LCx, respectively (all P<0.001). Despite this difference in image quality, mean scores for both CAf and NSR were weighted toward the high quality end of the scale. CONCLUSION: By 320-slice CT, the overall length of visualized coronary arteries, motion artifact-free length, and image quality using a 5-point scale showed values equal to or slightly lower in CAf than in NSR, but the absolute values were quite acceptable in both groups. PMID- 20299117 TI - Safety and efficacy of G-CSF in patients with ischemic heart failure: the CORNER (Cell Option For Recovery in the Non-Eligible Patients for Revascularization) study. AB - BACKGROUND: Demonstration that the heart is not a post-mitotic organ has led to clinical trials trying to obtain myocardial repair even in patients with heart failure. AIM OF THE STUDY: To evaluate as a less invasive method for promoting cardiac repair. METHODS: Thirteen patients with ischemic heart failure in NYHA and/or CCS classes >= 3 unsuitable for revascularization received G-CSF, as a compassionate use, in addition to optimal medical therapy. Symptoms and cardiac perfusion by gated-SPECT were assessed at baseline and at 4 month follow up. RESULTS: G-CSF was generally well tolerated. NYHA and CCS classes improved significantly from 3 (IR 2.5-3) to 2 (IR 1-2.5) (p = 0.012) and from 3 (IR 1-3) to 1 (IR 1-2) (p = 0.033). Heart failure severity symptoms according to the Minnesota Living with Heart Failure Questionnaire scores exhibited a non significant improvement from 52 +/- 27 to 39 +/- 26 (p = 0.15). At the Seattle Angina Questionnaire scores (ranging from 0 to 100, higher scores indicating better status), physical limitation improved from 39 +/- 31 to 64 +/- 29 (p = 0.03), angina stability from 42 +/- 29 to 64 +/- 28 (p = 0.05), angina frequency from 53 +/- 33 to 73 +/- 26 (p = 0.04), treatment satisfaction from 67 +/- 29 to 83 +/- 21 (p = 0.07), disease perception from 37 +/- 29 to 66 +/- 26 (p = 0.007). Quality of life assessed by a Visual Analogue Scale improved from 33 +/- 24 to 64 +/- 20 mm (p = 0.003). Stress and differential regional perfusion scores improved significantly from 1.78 +/- 1.38 to 1.66 +/- 1.38 (p = 0.05) and from 0.35 +/- 0.68 to 0.23 +/- 0.53 (p = 0.02) respectively. CONCLUSIONS: In patients with ischemic heart failure unsuitable for revascularization, G-CSF is associated to a significant improvement of symptoms, possibly reducing stress-induced ischemia. PMID- 20299118 TI - Pulmonary veins of the patients with atrial fibrillation: dual-source computed tomography evaluation prior to radiofrequency catheter ablation. PMID- 20299119 TI - Comparison of post amputation outcome in patients with type 2 diabetes from specialized foot care centres in three developing countries. AB - OBJECTIVE: To evaluate post amputation outcome and associated complications in type 2 diabetic patients who had undergone major amputations in developing countries. PATIENTS AND METHODS: A total of 526 (M:F; 369:157) subjects from three centers [India (IND), n=194, Bangladesh (BAN) n=177 and Tanzania (TAN) n=155 who had undergone amputation and subsequently visited the hospital were included in this analysis. Details on foot problems and associated complications were recorded. RESULTS: The prevalence of amputations was similar in all centres. The history of minor amputation and foot deformity was high in BAN. Recurrence of foot ulceration was more in TAN (30%) than in IND (9%) and BAN (11%). Re amputation rate was similar in all groups (3%). The use of artificial limb was most in BAN (97%). Myocardial infarction was more prevalent in IND (15%). In Tanzania, 31% had died during the follow-up period and it was 16% and 5% in IND and BAN. The causes of death were infection due to septicemia and cardiovascular events which finally led to multisystem organ failure. CONCLUSION: The outcome following a major diabetic foot amputation was compared in three developing countries. Recurrence of foot infection was common in Tanzania. The most frequent causes of death were infection and cardiovascular events. PMID- 20299105 TI - Vitrectomy outcomes in eyes with diabetic macular edema and vitreomacular traction. AB - PURPOSE: To evaluate vitrectomy for diabetic macular edema (DME) in eyes with at least moderate vision loss and vitreomacular traction. DESIGN: Prospective cohort study. PARTICIPANTS: The primary cohort included 87 eyes with DME and vitreomacular traction based on investigator's evaluation, visual acuity 20/63 20/400, optical coherence tomography (OCT) central subfield >300 microns and no concomitant cataract extraction at the time of vitrectomy. METHODS: Surgery was performed according to the investigator's usual routine. Follow-up visits were performed after 3 months, 6 months (primary end point), and 1 year. MAIN OUTCOME MEASURES: Visual acuity, OCT retinal thickening, and operative complications. RESULTS: At baseline, median visual acuity in the 87 eyes was 20/100 and median OCT thickness was 491 microns. During vitrectomy, additional procedures included epiretinal membrane peeling in 61%, internal limiting membrane peeling in 54%, panretinal photocoagulation in 40%, and injection of corticosteroids at the close of the procedure in 64%. At 6 months, median OCT central subfield thickness decreased by 160 microns, with 43% having central subfield thickness <250 microns and 68% having at least a 50% reduction in thickening. Visual acuity improved by > or =10 letters in 38% (95% confidence interval, 28%-49%) and deteriorated by > or =10 letters in 22% (95% confidence interval, 13%-31%). Postoperative complications through 6 months included vitreous hemorrhage (5 eyes), elevated intraocular pressure requiring treatment (7 eyes), retinal detachment (3 eyes), and endophthalmitis (1 eye). Few changes in results were noted between 6 months and 1 year. CONCLUSIONS: After vitrectomy performed for DME and vitreomacular traction, retinal thickening was reduced in most eyes. Between 28% and 49% of eyes with characteristics similar to those included in this study are likely to have improvement of visual acuity, whereas between 13% and 31% are likely to have worsening. The operative complication rate is low and similar to what has been reported for this procedure. These data provide estimates of surgical outcomes and serve as a reference for future studies that might consider vitrectomy for DME in eyes with at least moderate vision loss and vitreomacular traction. PMID- 20299120 TI - Association between screen time and metabolic syndrome in children and adolescents in Korea: the 2005 Korean National Health and Nutrition Examination Survey. AB - OBJECTIVE: To examine the association between screen time and the metabolic syndrome (MetS) in a nationally representative sample of children and adolescents. METHODS: A cross-sectional survey was conducted in 845 children and adolescents (10-18 years of age) from the 2005 Korean National Health and Nutrition Examination Surveys (KNHANES). Screen time was defined as TV time+computer time. The definition of MetS was based on the modified criteria used by the National Cholesterol Education Program-Adult Treatment Panel III, using age- and sex-specific values for some of the criteria. RESULTS: In comparison with the children and adolescents in the ST-Q1 (or=35h for a week) was 2.23 (95% CI, 1.02-4.86) after the adjustment for age, household income, and residence area. Moreover, screen time for a weekend day was also strongly associated with the prevalence of MetS, but not for a weekday. CONCLUSIONS: Screen time was independently associated with an increased prevalence risk of MetS in children and adolescents in Korea. Public health intervention to reduce screen time particularly for a weekend may be needed to prevent pediatric MetS in Korea. PMID- 20299121 TI - PC-based asymmetry analyzer for facial palsy study in uncontrolled environment: a preliminary study. AB - We develop a PC-based quantitative asymmetry analyzing system for facial palsy patients. To collect frequent data, the system is designed to maximize the chance of measure and minimize the variation of measuring. The system is based on the DirectX technology adopting white balance correction, lip segmentation, point tracking techniques. The degree and pattern of asymmetry is estimated by tracking the bi-lateral lip points. Tracking performance is tuned up by changing the configuration of tracking compared to previous study. All data are able to be sent via FTP and reviewed by clinician. DirectX technology makes it measure anywhere. White balance correction is effective in restoring color distortion and lip segmentation by region growing is effective in finding bi-lateral lip points but not in all environments. Point-tracking is a good method to provide the temporal movement of lip. A larger searching window of tracking points shows an improved performance in point of variation and robustness at fast movements. Transferring via Internet makes monitor the patient frequently. PC-based analyzing system is able to use not just in clinic but also at home. The system makes it possible to measure frequently and objectively and leads to diagnose exact conditions of patient. PMID- 20299122 TI - Adsorption of active ingredients of surface disinfectants depends on the type of fabric used for surface treatment. AB - The disinfection of surfaces in the immediate surrounding of a hospitalised patient is considered to be an important element for prevention of nosocomial infection. The type of fabric in a mop, however, has to our knowledge never been regarded as relevant for an effective disinfection of surfaces. We have therefore studied the adsorption of benzalkonium chloride (BAC), glutardialdehyde and propan-1-ol from working solutions of three surface disinfectants to four different types of fabric (A: white pulp and polyester; B: viscose rayon; C: polyester; D: mixture of viscose, cellulose and polyester). The working solutions of each disinfectant were exposed to each fabric for up to 24h. Before and after exposure, tissues were removed and squeezed in a standardised way. The eluate was used for determination of the concentration of the active ingredient in quadruplicate. The analysis of glutardialdehyde and BAC was performed using high performance liquid chromatography; the analysis of propan-1-ol was done using gas chromatography. BAC was strongly adsorbed to the tissues based on white pulp (up to 61% after 30 min), followed by the viscose rayon tissues (up to 70% after 30 min) and the mixed tissues (up to 54% after 7h). The polyester fibre tissue adsorbed the smallest amounts of BAC with up to 17% after 15 min. Only with the polyester fibre tissue were BAC concentrations found in the range of the calculated BAC concentrations. Glutardialdehyde and propan-1-ol did not adsorb to any of the fibres. Effective surface disinfection also includes selection of an appropriate fabric. PMID- 20299123 TI - When are the hands of healthcare workers positive for methicillin-resistant Staphylococcus aureus? AB - Hand hygiene is a key component in reducing infection. There are few reports on the prevalence of methicillin-resistant Staphylococcus aureus (MRSA) on healthcare workers' (HCWs') hands. The aim of this study was to establish whether HCWs' fingertips were contaminated with MRSA in a clinical hospital setting. The study was conducted in an acute tertiary referral hospital on four MRSA wards that were part of a larger research study on MRSA epidemiology and four other wards not included in the study. The fingertips from all categories of 523 HCWs were sampled on 822 occasions by the imprinting of fingertips on MRSA chromogenic agar plates. The type of hand hygiene agent used, if any, and the immediate prior activity of the HCW were recorded. Overall, 38/822 (5%) fingertips from 523 HCWs were MRSA-positive; 12/194 (6%) after clinical contact, 10/138 (10%) after contact with the patient's environment and 15/346 (4%) after no specific contact. MRSA was recovered on 2/61 (3%) occasions after use of alcohol hand rub, 2/35 (6%) after 4% chlorhexidine detergent, 7/210 (3%) hand washing with soap and water, and 27/493 (5%) when no hand hygiene had been performed. MRSA was recovered from HCWs on seven of the eight wards. MRSA was more frequently present on fingertips on the four non-study wards vs the four MRSA study wards [18/250 (7%), 3/201 (1%), respectively; P80 years (0.30; 0.10-0.93) compared with those aged 60-80 years. These findings suggest that although initially successful in some cases, the protocol used did not result in long-term clearance of MRSA carriage for most patients. PMID- 20299135 TI - Product evaluation of a new chlorhexidine gluconate transparent intravenous line dressing. PMID- 20299136 TI - Determinants of hand grip strength, knee extension strength and functional status in cancer patients. AB - BACKGROUND & AIMS: Decreased functionality and muscle weakness are prominent features in cancer patients. We investigated determinants of muscle function assessed by hand grip and knee extension strength as well as functional status in cancer patients. METHODS: 189 consecutively admitted cancer patients (age 60.8 +/ 12.7 years, 96 male) were recruited. Muscle function was assessed by hand grip and knee extension strength, and percentage of anticipated peak expiratory flow (%PEF). Functional status was determined by the EORTC questionnaire of quality of life. Nutritional status was assessed with Subjective Global Assessment (SGA). Age, gender, SGA, body mass index, clinical variables such as cancer location, presence of distant metastases, tumour burden according to TNM stage, UICC stage, number of drugs per day, number of comorbidities, type of treatment and depression were investigated as potential risk factors for muscle weakness and impaired functional status in a multiple regression analysis. RESULTS: 80 patients (39 male) were classified moderately or severely malnourished. Malnutrition also emerged as an independent determinant for hand grip (estimated effect size 11%, p < 0.01), knee extension strength (estimated effect size 12%, p < 0.001), and peak expiratory flow (estimated effect size 30%, p < 0.008) and functional status (estimated effect size 19.4%, p < 0.001) next to age and gender, which were the strongest predictors. Among the disease parameters, only amount of daily medication exhibited a significant influence on knee extension strength. CONCLUSIONS: Malnutrition is a disease independent risk factor for reduced muscle strength and functional status in cancer patients. Treatment of malnutrition might therefore also restore muscle strength. PMID- 20299137 TI - Ordeal by post or valuable research? An e-mail survey of consultant oral and maxillofacial surgeons' views of postal questionnaires examining their clinical practice. PMID- 20299138 TI - Donor pretreatment with dopamine and graft function following kidney transplant: a strategy to improve transplant outcomes? PMID- 20299139 TI - Social disparities and cause-specific mortality during economic development. AB - Social patterning of disease is pervasive and persistent. Disease patterns change with economic development and the attendant epidemiological transition. It is becoming evident that social patterns of disease are epidemiologically stage specific. In a population with a recent history of rapid economic development we examined social patterns of all-cause and cause-specific mortality over time to elucidate how economic development impacts disparities in health. We used concentration indices to provide a summary measure of disparities by income in potential years of life lost (PYLL) for the Hong Kong population from 1976 to 2006. For all-cause mortality and for each of the specific causes considered the concentration curve in 2006 dominated the 1976 concentration curve. The concentration index for all-cause PYLL was negligible in 1976, but increased over the period. PYLL attributable to injury and poisoning was fairly consistently associated with lower income, but PYLL attributable to cardiovascular diseases and cancer reversed from an association with higher income in 1976 to an association with lower income in 2006. Social disparities in health are not universal or homogeneous in origin. Attention should be focused on disease specific causes of disparities, so that contextually specific prevention strategies can be implemented. This is of particular relevance to China and other emerging economies where there may be a window of opportunity to prevent disparities in cancer and cardiovascular diseases occurring. PMID- 20299140 TI - Fertility history and cause-specific mortality: a register-based analysis of complete cohorts of Norwegian women and men. AB - The relationship between women's reproductive histories and later all-cause mortality has been investigated in several studies, with mixed results. Some studies have also considered cause-specific mortality and some have included men, but none has done both. We analyse associations between parity and age of first birth for women and men across 11 cause-of-death groupings using Norwegian register data for complete cohorts born 1935-1968 whose mortality was observed 1980-2003 (i.e. at ages 45-68). Age, period, educational level, marital status, region of residence and population size of municipality were included as co variates. In total, there were 63,000 deaths. Results showed that relative to parents of two children, childless men and women and those with one child had higher mortality risks for nearly all cause of death groupings. High parity (4+ children) was associated with raised male mortality from accidents and violence and higher mortality from cancer of the cervix among women. For other cause and gender groupings there was either little difference between those with two children and those of higher parities or an overall negative association between parity and mortality. Among men with the lowest level of education, however, high parity was positively associated with mortality from circulatory diseases. For all causes except female breast cancer, there was an inverse association between age at first birth and mortality risk. Similarities observed across cause groups and for women and men suggest that much of the fertility-mortality relationship is a result of selection or effects of reproductive behaviour on lifestyle. The latter may include both beneficial effects and harmful stress responses. However, physiological mechanisms are most probably important for some causes of death for women. Research on associations between parenting histories, health related behaviours, social support exchanges and reported or measured stress is needed to clarify mechanisms underlying the associations reported here. PMID- 20299141 TI - Local environments as determinants of walking in Melbourne, Australia. AB - Structural changes to neighbourhoods that promote walking are likely to benefit everyone in a community and result in long-term improvements in the population's physical activity and health. We consider time spent walking in relation to objectively measured features of people's local environments (functionality, safety, destinations and aesthetics) in Melbourne, Australia. We used multilevel ordered logistic regression analysis to examine variations in time spent walking amongst 2334 residents of 49 small areas (Census Collection Districts - CCDs). Features on each street segment within a 400 m radius of a randomly selected household within each CCD were measured, supplemented by geographic information system data. Models were adjusted for socio-demographic and socio-economic characteristics of individual and socio-economic characteristics of areas. We found that increasing track length, having paths located closer to roads, fewer buildings with driveways, a greater presence and variety of destinations and views of shops, light industry, offices and/or schools (commercial views) were associated with more time spent walking in local environments in adjusted models. As such, each of the four features of local environments considered (design, safety, destinations and aesthetics) were associated on at least one measure with walking. Characteristics of areas reflecting urbanisation (destinations, commercial views, path location and driveways) were associated with increased time spent walking. This study provides important evidence on how urban design can be utilised to improve physical activity. PMID- 20299142 TI - Do working mothers raise couch potato kids? Maternal employment and children's lifestyle behaviours and weight in early childhood. AB - Alarm about the increasing prevalence of childhood obesity has focussed attention on individual lifestyle behaviours that may contribute to unhealthy weight. More distal predictors such as maternal employment may also be implicated since working mothers have less time to supervise children's daily activities. The research reported here used two waves of data from the Longitudinal Study of Australian Children to investigate whether mothers' hours in paid work shape young children's television viewing, snacking and physical activity, and through those lifestyle behaviours, children's weight at ages 4-5 years and 6-7 years. At both ages, children's lifestyle behaviours were interrelated and associated with weight status. Cross-sectional analysis confirmed small, direct associations between longer hours of maternal employment and child weight at age 4-5 years, but not with child's weight measured two years later. In both the cross-sectional and prospective analyses, the children of mothers who worked part-time watched less television and were less likely to be overweight than children of mothers who were not employed or who worked full-time. While associations were small, they remained significant after adjustment for maternal weight, household income and other factors. The combination of direct and indirect relationships between mothers' work hours and the weight status of their young children provides additional support to calls for family-friendly work policies as an important means for promoting healthy family lifestyles and early childhood wellbeing. PMID- 20299143 TI - Illness reporting and demand for medical care in rural Burkina Faso. AB - The issue of illness reporting in modelling demand for health care in low- and middle-income countries can be handled according to either of two conceptually different constructs: (a) considering illness reporting behaviour as endogenous to demand; or (b) considering demand itself as the outcome of a sample selection phenomenon. In this paper, we take the second viewpoint and estimate the demand for medical care with an estimator that uses Heckman-type. Empirical estimates based on household survey data from rural Burkina Faso suggest that there are some implications of illness reporting behaviour for modelling the demand for medical care. PMID- 20299144 TI - Body temperature effects on lung injury in ventilated preterm lambs. AB - AIMS: Mechanical ventilation causes lung injury in premature infants. Hypothermia may protect against and hyperthermia may augment lung injury. We tested the effects of hypo- and hyperthermia on ventilation induced acute lung injury in preterm lambs. METHODS: Twin sheep fetuses at 128 d GA (term 150 d) were surgically delivered and randomized to unventilated control (UVC), normothermia (38-39 degrees C) without lung injury (NTNI), or to 1 of 3 injurious ventilation groups: hypothermic (33-34 degrees C, LT), normothermic (38-39 degrees C, NT) or hyperthermic (40-41 degrees C, HT). NT, LT and HT groups had 15 min of injurious ventilation (PEEP 0 cmH(2)O, V(T) escalation to 15 mL/kg) following delivery and prior to surfactant. The animals were then gently ventilated (PEEP 5cmH(2)O, V(T) 7.5 mL/kg) for 2h 45 min. NTNI lambs received surfactant at birth prior to gentle ventilation. The lambs were then euthanized, and bronchoalveolar lavage (BAL) fluid and lung tissue were used to evaluate lung injury, inflammatory cell counts, inflammatory markers and cytokine mRNA. RESULTS: Target temperatures were achieved by 15 min of age and maintained for 3h. All ventilated groups had increased BAL protein, lung inflammation and increased cytokine mRNA. HT animals developed acidosis, premature death, pneumothoraces, impaired lung function and increased inflammatory mRNA expression. LT animals remained clinically stable without pneumothoraces or death, had improved ventilatory efficiency and trended toward lower inflammatory mRNA expression than NT animals. CONCLUSION: Hyperthermia exacerbated ventilator induced lung injury, while hypothermia may protect against lung injury in the preterm lamb. PMID- 20299146 TI - Assessment of temporal trends in ecosystem health using an holistic indicator. AB - The Ecosystem Approach to environmental management, with its explicit acknowledgment of the environmental, social and economic elements within ecological systems, is becoming increasingly adopted by managers and policy makers. However, there are few specific prescriptions as to exactly how these different elements should be integrated, or examples where historical changes have been tracked. Here, we assess the potential benefits and challenges of applying an Ecosystem Approach to management using one particular method, the Holistic Ecosystem Health Indicator (HEHI), which integrates data from the ecological, social and interactive dimensions into a single composite index of ecosystem 'health'. We apply it to one of the best-documented catchments in the UK, the Ythan Estuary in Aberdeenshire, Scotland, based on a 50-year time series of data. The evaluation of ecosystem health over time is lacking in previous applications of HEHI, yet is crucial for the assessment of the utility of this approach to ecosystem management. The application of HEHI yielded different insights to those revealed from the traditional application of biophysical approaches for managing the Ythan. Overall, ecological health declined through the 50-year period, although it increased marginally in the last decade, while social and interactive dimensions followed the opposite trend. HEHI indicated a steady increase in ecosystem health overall except for the last decade, when it declined marginally. Our evaluation of the application of ecosystem health for the Ythan revealed major data gaps. For the approach to be used more widely, issues of data availability and the temporal and geographical mismatch between ecological and social research boundaries need to be overcome. PMID- 20299147 TI - Outcome predictors of radical prostatectomy in patients with prostate-specific antigen greater than 20 ng/ml: a European multi-institutional study of 712 patients. AB - BACKGROUND: Prostate cancer (PCa) patients with pretreatment prostate-specific antigen (PSA) >20 ng/ml have a high risk of biochemical and clinical failure and even cancer-related death after local therapy. Pretreatment predictors of outcome after radical prostatectomy (RP) in this patient group are necessary. OBJECTIVE: Our aim was to assess how the use of additional high-risk factors (biopsy Gleason score [bGS] > or = 8 or clinical stage 3-4) can improve prediction of treatment failure and cancer-related death after RP in patients with PSA >20. DESIGN, SETTING, AND PARTICIPANTS: In a retrospective multicentre cohort study from six European centres between 1987 and 2005, 712 patients with PSA >20 ng/ml underwent RP and bilateral pelvic lymphadenectomy. MEASUREMENTS: Subgroups were analysed to determine the relationship between the number of high-risk factors and histopathology, biochemical progression-free survival, clinical evidence of progressive disease, prostate cancer-specific mortality (PCSM), and overall mortality. Kaplan-Meier analysis with log-rank test and Cox multivariable analysis were applied. RESULTS AND LIMITATIONS: Median follow-up was 77 mo. The number of high-risk factors was significantly associated with unfavourable histopathology. Among patients with only PSA >20 ng/ml, 33% had pT2 PCa, 57.9% had bGS <7, 54% had negative surgical margins, and 85% were lymph node negative (pN0), whereas among patients with all three high-risk factors, 4.5% had pT2 PCa, 2.3% had bGS <7, 20.5% had negative margins, and 49% were pN0 (p<0.001). The strongest predictor of progression and mortality was bGS. PSA >20 ng/ml associated with bGS < or =7 resulted in 10-yr PCSM of 5%; when associated with bGS > or =8, PCSM was 35%. The main limitations of the study were retrospective design and varying treatment modalities. CONCLUSIONS: PCa patients with PSA >20 ng/ml have varying risk levels of disease progression and PCSM. Considering additional risk factors further stratifies this group into four subgroups that can guide the clinician in preoperative patient counselling. PMID- 20299149 TI - Laboratory and field evaluation of Metarhizium anisopliae (Deuteromycotina: Hyphomycetes) for the control of Rhipicephalus microplus (Acari: Ixodidae) in the Mexican tropics. AB - The aim of the present study was to evaluate the effect of Metarhizium anisopliae to control Rhipicephalus microplus under laboratory and field conditions (larvae on vegetation) in the Mexican tropics. In the laboratory study, Ma34, Ma14 and a mixture of Ma34+Ma14 strains of M. anisopliae were evaluated for their control of the adult and larval stages of R. microplus, using the adult and larval immersion test respectively. The reproductive efficiency index of engorged females was determined in the treated and control groups. In the adults, the Ma34 and MA14 strains both produced an efficacy of 100% on engorged females at 1 x 10(8), 1 x 10(7) and 1 x 10(6)conidia/ml; however, only Ma34 killed 100% at 1 x 10(6)conidia/ml dose. The mixture of both strains (Ma34+Ma14) produced an efficacy of 100% on engorged females at 1 x 10(8)conidia/ml. R. microplus engorged females treated with Ma34 and a mixture of strains Ma34 and Ma14 reduced egg oviposition by 55.5% and 39.1% respectively compared to treated controls (P<0.001). In the larval evaluation, Ma14 produced an efficacy of 45-62%; however, Ma34+Ma14 increased the efficacy reaching 90% (1 x 10(8)conidia/ml concentrations, P<0.05). In the field study, twelve 9 m(2) plots with vegetation were artificially infested with R. microplus larvae. Six plots were used as control and six as test areas. The treated plots received the Ma34+Ma14 (1 x 10(8)conidia/ml) by manual scattering at 0, 14 and 28 days post-treatment (PT). The number of larvae in the treated and control group was determined at 0, 7, 14, 21, 28 and 35 days PT by the tick drag method. This field study was carried out in two different seasons (January-March, wet, April-May, dry). In the wet season trial the efficacy of M. anisopliae to control R. microplus was 67.7% and 100% in the dry season trial .In conclusion, the mixture of Ma34 and Ma14 strains of M. anisopliae showed a high efficacy to control both larval and adult stages of R. microplus under laboratory conditions, and in field conditions these strains were efficient to control larval stages on vegetation. PMID- 20299148 TI - 3,3'-Diindolylmethane (DIM) inhibits the growth and invasion of drug-resistant human cancer cells expressing EGFR mutants. AB - Epidermal Growth Factor Receptor (EGFR) mutants are associated with resistance to chemotherapy, radiation, and targeted therapies. Here we found that the phytochemical 3,3'-Diindolylmethane (DIM) can inhibit the growth and also the invasion of breast cancer, glioma, and non-small cell lung cancer cells regardless of which EGFR mutant is expressed and the drug-resistant phenotype. DIM reduced an array of growth factor signaling pathways and altered cell cycle regulators and apoptotic proteins favoring cell cycle arrest and apoptosis. Therefore, DIM may be used in treatment regimens to inhibit cancer cell growth and invasion, and potentially overcome EGFR mutant-associated drug resistance. PMID- 20299150 TI - Effect of extra dietary lysine in Ascaridia galli-infected grower layers. AB - The hypothesis examined in this study was that extra dietary lysine (Lys) above the recommended standard exerts beneficial effects on the defence reactions, growth performance and nutrient utilization in Ascaridia galli-infected chickens. Therefore, 1-day-old female Lohmann Selected Leghorn chickens were at first fed standard Lys diet (8.5 g Lys/kg DM). At 4 weeks of age, the birds were allocated to groups 1 and 3, both being continued on standard Lys diet, whereas birds in groups 2 and 4 were switched to extra Lys diet (10.5 g Lys/kg DM). Birds in groups 3 and 4 were additionally infected at this age (4 weeks) with 250 embryonated eggs of A. galli. All the birds were slaughtered 7-week-post infection (p.i.) at an age of 11 weeks. Infected birds on standard Lys diet consumed more feed and reached a similar level of Lys intake as birds on extra Lys diet 7-week-p.i. Utilization of feed, crude protein, and Lys for body weight (BW) gain was adversely affected in infected birds on standard Lys diet (P<0.001). Extra Lys diet reduced the incidence of infection (P<0.05), but worm counts, worm length, faecal egg counts and female worm fecundity were not different between the infected groups (P>0.05). Extra Lys diet led to higher final BW in uninfected and infected birds (P<0.05). It is concluded that extra Lys above the normal recommended standard supports the defence reactions and compensates the negative effect of infection on growth performance and nutrient utilization in A. galli-infected birds. PMID- 20299151 TI - Changes in the frequency of the G137D and W251S mutations in the carboxylesterase E3 gene of Cochliomyia hominivorax (Diptera: Calliphoridae) populations from Uruguay. AB - The New World Screwworm (NWS) fly Cochliomyia hominivorax is one of most important myiasis-causing flies in the Neotropics. It is responsible for severe losses to the livestock industry through both mortality and the loss of productivity of infested animals. In Uruguay, NWS represents a significant problem. To date this pest has been controlled by the application of chemical insecticides, mainly the pyrethroid and organophosphate (OP) classes. However, the intensive use of these compounds over many years has led to the evolution of resistance which has the potential to compromise the effectiveness of current control strategies. One mechanism by which resistance has occurred in this and related dipteran species is through two mutations (G137D and W251S) in the carboxylesterase E3 enzyme that have enhanced ability to hydrolyze certain insecticides. In this study changes in the frequency of these mutations in C. hominivorax was investigated in three different Uruguayan regions in 2003 and 2009. All three regions analyzed showed a reduction in the frequency of the G137D mutation and a significant increase in frequency of the W251S mutation, and this may be related to the current intense use of dimethyl-OP and pyrethroid insecticides. The findings of this study provide current information on the frequency of these resistance-associated mutations in NWS in Uruguay and may help select appropriate chemicals for NWS control as part of potential pest management strategies. PMID- 20299152 TI - Comparative virulence of Nosema ceranae and Nosema apis in individual European honey bees. AB - Nosema apis and Nosema ceranae are intracellular microsporidian parasites infecting the midgut epithelial cells of adult honey bees. N. ceranae was considered to be restricted to the Asian honey bee, Apis cerana, but is nowadays a parasite found also in the European honey bee (Apis mellifera) across most of the world. Recent surveys and experimental work suggest that N. ceranae is a serious threat to the global beekeeping industry. It has been suggested that N. ceranae induces significantly higher mortality in honey bees than N. apis, but little is known about their comparative virulence. In this study, we used in vivo infection experiments to study the two parasites' different virulence (i.e. multiplication rate and infectivity). A qPCR was developed to elucidate within host competition between the two parasites using mixed infections. The outcome of the experiments indicates minor differences in infectious dose and multiplication rate between the two species. Moreover, the mortality caused by N. ceranae was not significantly higher than for N. apis and N. ceranae appeared to have no competitive advantage within host. PMID- 20299153 TI - Patient controlled sedation using a standard protocol for dressing changes in burns: Patients' preference, procedural details and a preliminary safety evaluation. Are studies always adequately powered and analyzed? PMID- 20299154 TI - The application of glycerol-preserved skin allograft in the treatment of burn injuries: an analysis based on indications. AB - INTRODUCTION: Glycerol-preserved skin allograft (GPA) plays a crucial role in the management of burns. Its indications include wound-bed preparation, definitive dressing and sandwich grafting technique. OBJECTIVE: We analysed the experience of using GPA and its efficacy in burn treatment in our burn centre. METHODS: All burns managed with GPA in our burn centre from October 2001 to May 2008 were analysed. RESULTS: Mean total body surface area (TBSA) of 43 consecutive cases was 28.7%. GPA adhered to the wound for an average of 8.4 days before rejection. The length of hospital stay of the survivors was 42.5 days. The autograft take after wound-bed preparation with GPA was 88.4%. For sandwich grafting technique, the autograft take was 74.4%. When GPA was applied for partial-thickness burn as definitive dressing, all patients achieved complete healing within an average of 19 days without further surgical intervention. Despite colonisation of burn wounds after application of skin allograft, the outcomes of autograft take and wound healing were not significantly different. CONCLUSION: The selective and strategic use of the GPA in major burn patients ensures optimal benefits in the management of burns. It is versatile in various categories of burn wounds with minimal morbidity. PMID- 20299155 TI - Gene-expression profiles, tumor microenvironment, and cancer stem cells in breast cancer: latest advances towards an integrated approach. AB - During the past decade, several high throughput analytical methods for gene expression profiling have been developed. DNA microarrays and multiplex RT-PCR have been applied in the field of breast-cancer research to establish new molecular taxonomic classifications, or a selected group of genes able to predict the prognosis of the patients and/or their response to chemotherapy. This technology provides an opportunity to refine the anti-neoplastic treatment and avoid the currently observed under- and over-treatment of breast-cancer patients. In parallel, high throughput technologies for gene-expression analysis have been applied to research on cancer stem cells (CSCs) and the tumor microenvironment, offering a wider vision of the molecular processes that influence carcinogenic events, disease development, and the response to the treatment of breast-cancer patients. In this report, we briefly revisit the most relevant genomic studies on breast-cancer prognosis and prediction to introduce the latest advances in tumor dormancy, its implications in the clinical outcome of disease-free patients and its connection with CSCs biology and microenvironment influence in the metastatic process. Finally, we have discussed the contribution of the results of these studies to the design of new experimental strategies oriented towards personalized medicine. PMID- 20299156 TI - Maternal and umbilical cord androgen concentrations do not predict digit ratio (2D:4D) in girls: a prospective cohort study. AB - Digit ratio (2D:4D) is widely used as a marker of prenatal androgen exposure. However, there are no published prospective studies where prenatal androgen exposure has been measured and correlated with digit ratio in adult life. We aimed to establish the prospective relationship between prenatal androgen exposure in the second and third trimesters of pregnancy (as measured by maternal circulating androgen concentrations and umbilical cord androgen concentrations) and digit ratio in adolescent girls. Androgen concentrations (testosterone, free androgen index, androstenedione, DHEAS) and sex hormone binding globulin (SHBG) were measured in stored plasma samples from pregnant mothers at 18 (n=118) and 34/36 (n=114) weeks of gestation and in cord blood (n=82) from the Western Australian Pregnancy (Raine) Cohort Study (www.rainestudy.org.au). Digit ratio was measured in 244 female offspring from this cohort at age 14-16 years. Only one borderline statistically significant correlation between maternal circulating androstenedione levels at 18 weeks of gestation and left hand digit ratio was seen. No other statistically significant relationship between maternal androgen concentrations or umbilical cord androgen concentrations and digit ratio in adolescence were observed. These findings suggest that variation in 2D:4D in girls is not established as a result of testosterone concentrations in the second and third trimesters. We conclude that prenatal androgen exposure as measured by maternal circulating androgen concentrations at 18 and 34/36 weeks of gestation or in the umbilical cord at birth may not predict digit ratio in girls. PMID- 20299157 TI - Neuroticism and conscientiousness are associated with cortisol diurnal profiles in adults--role of positive and negative affect. AB - A substantial body of research on the pathophysiology of negative health outcomes has focused on dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis. Maladaptive and adaptive personality features have been discussed to be associated with health outcomes. In the current study, we investigated the association of neuroticism (N) and conscientiousness (C) with diurnal cortisol levels in 102 working parents (M age=37 years; 50% female). Further, we examined the impact of daily positive and negative affect on this association. During a 6 day time-sampling phase, cortisol was measured at awakening and after that within intervals of 3h. We found a positive association of N with cortisol levels throughout the measurement period, but no association of C with daily cortisol. When accounting for daily positive and negative affect, individuals with high scores on C displayed reductions in daily cortisol concentrations that were driven by positive affect compared to individuals with low C scores. No such association emerged for N. Our findings might further elucidate the role of personality in HPA axis regulation and improve our understanding of the association of endocrine states and health outcomes. PMID- 20299158 TI - Low plasma lactate concentration as a biomarker of an incompetent brain-pull: a risk factor for weight gain in type 2 diabetes patients. AB - OBJECTIVE: Body weight development is closely regulated by central nervous mechanisms. As has been demonstrated recently, the capability of the brain to actively demand energy from the body (brain-pull) is indispensable for the maintenance of systemic homeostasis. A deficit in this brain-pull may result in compensatory ingestive behavior followed by weight gain in the medium or long term. The aim of this study was to establish a biomarker of such an incompetent brain-pull. Since lactate is an alternative cerebral energy substrate to glucose, we investigated whether low fasting plasma lactate concentrations are associated with weight gain and increased feelings of hunger in patients with type 2 diabetes over a 3-year period. METHODS: In a population based cohort study 134 type 2 diabetes patients were examined at baseline and 3-year follow-up. Plasma lactate concentrations and additional hormones associated with food intake such as e.g. insulin, or leptin, as well as psychological variables like hunger feelings before and after a standardized breakfast were measured. The relation between fasting plasma lactate concentrations and postprandial hunger as well as follow-up weight was analyzed. RESULTS: Low fasting plasma lactate concentrations predicted a higher 3-year follow-up weight (B=-1.268, SE=0.625, p=0.04). Moreover, low fasting plasma lactate concentrations were associated with more pronounced feelings of postprandial hunger (B=-0.406, SE=0.137, p<0.01). CONCLUSIONS: We conclude that low plasma lactate concentrations may represent a biomarker of an incompetent brain-pull, which is associated with weight gain and increased postprandial hunger in patients with type 2 diabetes mellitus. These results are in line with the view that plasma lactate can be used by the brain as an alternative energy substrate and thereby to some extent prevent overeating and obesity. PMID- 20299159 TI - Arachnoid granules: Dandy was Dandy, Cushing and Weed were not. AB - Errors can be instructive. It seems that Harvey Cushing and Louis Weed provided the medical world with a faulty theory of cerebrospinal fluid absorption. Louis Weed, working in Harvey Cushing's laboratory, initially studied the movement of substances in the cerebrospinal fluid by using low-pressure studies. Results of the low-pressure studies were considered unsatisfactory and high pressure experiments were undertaken and these had results similar to earlier work done by others in human cadavers. High pressure results demonstrating movement of fluid through the arachnoid granules were deemed correct. Because of Cushing's position of authority, the theory became accepted as fact and in time proved to be entrenched dogma. Walter Dandy demonstrated in experiments on hydrocephalus and the surgical removal of the arachnoid granule system that the fluid was produced by the choroid plexuses and not absorbed by the arachnoid granules. His work was dismissed by Weed as unreliable. Examination of the pattern of deposition of corpora amylacea on the surface of the brain provides evidence that cerebrospinal fluid does not pass through arachnoid granules but passes through the choroid fissure and is recycled through choroid plexus portals. The choroid plexus portal theory can explain the findings in the low-pressure experiments of Weed. Bias and pride seem to be the source of the faulty theory. Entrenched dogma is resistant to challenge. PMID- 20299160 TI - Chronic infection and the origin of adaptive immune system. AB - It has been speculated that the rise of the adaptive immune system in jawed vertebrates some 400 million years ago gave them a superior protection to detect and defend against pathogens that became more elusive and/or virulent to the host that had only innate immune system. First, this line of thought implies that adaptive immune system was a new, more sophisticated layer of host defense that operated independently of the innate immune system. Second, the natural consequence of this scenario would be that pathogens would have exercised so strong an evolutionary pressure that eventually no host could have afforded not to have an adaptive immune system. Neither of these arguments is supported by the facts. First, new experimental evidence has firmly established that operation of adaptive immune system is critically dependent on the ability of the innate immune system to detect invader-pathogens and second, the absolute majority of animal kingdom survives just fine with only an innate immune system. Thus, these data raise the dilemma: If innate immune system was sufficient to detect and protect against pathogens, why then did adaptive immune system develop in the first place? In contrast to the innate immune system, the adaptive immune system has one important advantage, precision. By precision I mean the ability of the defense system to detect and remove the target, for example, infected cells, without causing unwanted bystander damage of surrounding tissue. While the target precision per se is not important for short-term immune response, it becomes a critical factor when the immune response is long-lasting, as during chronic infection. In this paper I would like to propose new, "toxic index" hypothesis where I argue that the need to reduce the collateral damage to the tissue during chronic infection(s) was the evolutionary pressure that led to the development of the adaptive immune system. PMID- 20299161 TI - Comparison between locking and non-locking plates for fixation of metacarpal fractures in an animal model. AB - PURPOSE: The use of locking plates increases the primary load to failure, thereby reducing the rate of implant-related failure. The good clinical and biomechanical results of locking plates in long bones might be applicable to treatment of metacarpal fractures. The purpose of this study was to determine strength and stiffness of locking plates in a metacarpal fracture model with mono- and bicortical screw fixation in comparison to non-locking plate mono- and bicortical screw fixation, with both types of plates placed at the dorsal side of the bone. METHODS: Fresh second metacarpals from domestic pigs (n=40) were randomized in 4 equal groups. Short, oblique, mid-shaft fractures were generated, using a standardized 3-point bending method. Fractures were plated with non-locking, titanium, 1-mm-thick monocortical (group 1, n=10) or bicortical (group 2, n =10) plates (Leibinger-Stryker; Stryker Corp, Freiburg, Germany). Newly designed locking titanium plates with the same width and thickness (Leibinger-Stryker) were used in the same manner for groups 3 (monocortical) and 4 (bicortical). The metacarpals were then tested to load to failure in a cantilever bending mode. RESULTS: Bicortical, non-locking fixation (group 2, 359 +/- 90 N) had a higher load to failure than monocortical non-locking fixation (group 1, 250 +/- 56 N) in testing the maximum load to failure (p < .01). There was no significant difference in stiffness between group 1 (46 +/- 12 N/mm) and group 2 (56 +/- 21 N/mm). The difference in maximum load to failure between monocortical (group 3, 440 +/- 85N) and bicortical (group 4, 378 +/- 116 N) locking plate stabilization was not significant. Also, there was no significant difference in stiffness between monocortical (group 3, 83 +/- 35 N/mm) and bicortical locking plates (group 4, 70 +/- 31 N/mm). Comparing non-locking (group 1) and locking plates in a monocortical fixation technique (group 3) demonstrated significant differences in maximum load to failure (group 1, 250 +/- 56 N; group 3, 440 +/- 85 N) and stiffness (group 1, 46 +/- 12 N/mm; group 3, 83 +/- 35 N/mm). The stability of monocortical locking plates was stronger, although not statistically significant, than the non-locking bicortical plates (load to failure, 440 +/- 85 N vs 359 +/- 90 N; stiffness, 83 +/- 35 N/mm vs 56 +/- 21 N/mm). CONCLUSIONS: The new generation of locking plates can be used to achieve a higher stability for fixation of metacarpal fractures. Monocortical, stable fixation can minimize flexor tendon interference and probably reduce bone and soft tissue trauma. PMID- 20299162 TI - [Learning use of spatulas: risks of perineal injuries and newborns morbidity]. AB - OBJECTIVES: To examine the acute neonatal and maternal perineal morbidity due to resident training on spatulas assisted deliveries. MATERIAL AND METHODS: We conducted a retrospective observational study of succesful spatulas-assisted deliveries at Nice University Hospital between January2003 and December2006. We performed univariate analysis and logistic regression to assess risk of severe perineal injuries, vaginal laceration and newborn hospitalization according to operator status, controlling for confounders. RESULTS: Among 1004 deliveries, 86.4% were performed by residents. No significant difference was found on incidence of severe perineal tears between the 872 extractions performed by residents and the 132 performed by an attending physician (6.9% versus 7.9% p=0.706; OR=0.86 IC95% [0.41-1.81]), but extraction performed by young residents were associated to more severe perineal tears than those performed by senior residents (8.0% versus 4.5% p=0.035; OR=2.10 IC95% [1.16-3.77]). There was no difference between groups concerning newborn morbidity and hospitalisation in special care units (6.4% versus 9.8% p=0.149; OR=1.49 IC95% [0.73-304]). CONCLUSION: According to our data, training of resident do not increase the incidence of severe perineal injuries, neonatal complications and hospitalisation linked to spatulas assisted delivery. PMID- 20299163 TI - [Neurodegenerative polyglutamine expansion diseases: physiopathology and therapeutic strategies]. AB - Polyglutamine expansion diseases are adult-onset inherited neurodegenerative disorders that lead to death 10 to 20 years after the first symptoms. Currently, there is no therapy to fight against these diseases. They include Huntington's disease, spinobulbar muscular atrophy, dentatorubral-pallido-luysian atrophy and six types of spino-cerebellar ataxia. The diseases are caused by a unique mutational mechanism: an expansion of the CAG trinucleotide in the corresponding genes coding for an expanded tract of glutamine in the mutated proteins. Polyglutamine expansion confers to the mutant proteins toxic properties that cause neuronal cell death in brain regions specific to each disease. Thanks to cellular and animal models (fly, fish, mouse and rat) of these diseases, we have considerably improved our understanding of the toxic nature of polyglutamine expansion and the physiopathology, and we are now in position to design and test therapeutic strategies to prevent or delay the disease process. PMID- 20299164 TI - Person-environment interaction in the prediction of alcohol abuse and alcohol dependence in adulthood. AB - BACKGROUND: Behavioral disinhibition (externalizing/impulsivity) and behavioral inhibition (internalizing/anxiety) may contribute to the development of alcohol abuse and dependence. But tests of person-by-environment interactions in predicting alcohol use disorders are needed. This study examined the extent to which interactions between behavioral disinhibition, behavioral inhibition and family management during adolescence predict alcohol abuse and alcohol dependence at age 27. METHODS: This study used longitudinal data from a community sample of 808 men and women interviewed from ages 10 to 27 in the Seattle Social Development Project. Zero-order correlations followed by a series of nested regressions examined the relationships between individual characteristics (behavioral disinhibition and behavioral inhibition/anxiety) and environment (good vs. poor family management practices during adolescence) in predicting alcohol abuse and dependence criterion counts at age 27. RESULTS: Behavioral disinhibition and poor family management predicted increased likelihood of both alcohol abuse and alcohol dependence at age 27. Behavioral inhibition/anxiety was unrelated to both outcomes. Youths high in behavioral disinhibition were at increased risk for later alcohol abuse and dependence only in consistently poorly managed family environments. In consistently well-managed families, high levels of behavioral disinhibition did not increase risk for later alcohol abuse or dependence. CONCLUSIONS: Behavioral disinhibition increases risk for alcohol abuse and dependence in early adulthood only for individuals who experience poor family management during adolescence. Interventions seeking to reduce environmental risks by strengthening consistent positive family management practices may prevent later alcohol abuse and dependence among individuals at risk due to behavioral disinhibition. PMID- 20299165 TI - Evolution of infectious bronchitis virus in Taiwan: characterisation of RNA recombination in the nucleocapsid gene. AB - Avian infectious bronchitis virus (IBV) belongs to the Coronaviridae family and causes significant economic loss in Taiwan (TW), even in flocks that have been extensively immunised with Massachusetts (Mass)-serotype vaccines. Phylogenetic analysis of all non-structural and most structural genes shows that TW IBV is genetically distinct from the US strain and more similar to Chinese (CH) IBV. In contrast, the nucleocapsid (N) gene of TW IBV presents phylogenetic incongruence. RNA recombination at the 5' end of the N gene between TW and US IBV is shown to be responsible for this discordance. Surprisingly, the recombinant N gene is found in all of tested TW IBV isolates, suggesting that a recombination event gave origin to a founder lineage. Our data indicate that RNA recombination in the recombinant 5' end of the N gene may have caused the emergence of the current IBV population in Taiwan. PMID- 20299166 TI - RT-PCR diagnosis followed by sequence characterization of paramyxoviruses in clinical samples from snakes reveals concurrent infections within populations and/or individuals. AB - Paramyxoviruses (PMV) are important causes of disease in snakes in both private and zoologic collections and have been described in many different parts of the world. We have used the described L-gene nested RT-PCR (Ahne et al., 1999) as a diagnostic tool for the detection and characterization of PMV in clinical field samples from 102 snakes from Germany and Hungary. Fifty of the tested 203 samples were positive in the RT-PCR. 38 organs or swab samples from 25 snakes were selected for sequencing. They resulted in 13 different partial L-gene sequences, eight of which were identical to earlier characterized isolates, while five were new unique sequences, but also closely related to the earlier described PMV sequences. The comparison of sequences obtained from tissues from the same animal or from different animals from the same collection indicates that snakes can be infected with several different PMV during one outbreak. This is the first report of concurrent infection in a single snake or group of snakes with several distinct PMV. PMID- 20299167 TI - Determination of a new designer drug, N-hydroxy-3,4-methylenedioxymethamphetamine and its metabolites in rats using ultra-performance liquid chromatography-tandem mass spectrometry. AB - An N-hydroxy analogue of 3,4-methylendioxymethamphetamine (MDMA), N-hydroxy MDMA (N-OH MDMA), has recently been distributed as a new designer drug in some drug markets. Very little data is available to the metabolic and pharmacological properties of N-OH MDMA, although it has been reported that the N-demethyl analogue, N-hydroxy-3,4-methylenedioxyamphetamine (N-OH MDA), is mainly metabolized to MDA in rats. In this study, an analytical method for the determination of N-OH MDMA and its metabolites in biological samples was developed, and the metabolic properties of N-OH MDMA in rats were investigated. After the i.p. administration of N-OH MDMA to pigmented hairy rats (5mg/kg/day, 10 days), N-OH MDMA and its N-dehydroxy and N-demethyl metabolites (MDMA, N-OH MDA and MDA) in rat plasma, urine and hair samples were determined by ultra performance LC (UPLC)-MS/MS. The hair sample was extracted by 1-h sonication and overnight soaking in 5M hydrochloric acid-methanol (1:20). The plasma, urine, and hair extract samples were purified using a solid-phase extraction procedure. N-OH MDMA in the samples could be precisely analyzed by avoiding an alkaline environment. The parent compound very rapidly disappeared from the rat plasma (<15min) and urine (<10h), and most of the N-OH MDMA was excreted in the rat urine as MDMA and MDA in 72h. In the rat hair samples collected 4 weeks after the first administration, N-OH MDMA (0.03ng/mg) and N-OH MDA (0.13ng/mg) were clearly detected as well as MDMA (149ng/mg) and MDA (52ng/mg). This analytical method will be useful for the analysis of N-OH MDMA and its metabolites in biological samples. PMID- 20299168 TI - [Interstitial pneumonia related to mesalamine]. AB - We report the case of a 57-year-old woman with ulcerative colitis since eight years who developed a diffuse interstitial pneumonia linked to mesalazine (oral and enemas). The adverse drug-related effect to mesalazine was strongly suggested regarding improvement upon discontinuation and relapse after reinstitution of mesalazine. To date, after 8 years, the patient has not any respiratory symptom which is another argument for the adverse drug-related effect to mesalazine. PMID- 20299169 TI - [Enteric intussusception in an adult due to a lipoma]. PMID- 20299170 TI - [Appendicular mucocele: laparoscopic conversion and follow-up]. PMID- 20299171 TI - Long-term results of Malone's procedure with antegrade irrigation for severe chronic constipation. AB - AIM: The Malone antegrade colonic enema (MACE) procedure is a minimally invasive treatment for severe constipation, and the objective of the present study was to assess the long-term results and quality of life in patients undergoing such colonic irrigation. METHOD: Twenty-five adult patients underwent MACE between 1995 and 2002 for chronic constipation. After a mean follow-up duration of 55+/ 36 months, the patients answered questionnaires to assess stoma usage, constipation score (KESS) and quality of life (GIQLI). RESULTS: The mean quality of-life scores for these patients was 83+/-28 (normal: 125), while their mean constipation score was 19+/-9 (normal: <7). Twelve patients stopped the irrigations, and eight underwent further surgical procedures, specifically, total colectomy with ileostomy (n=2), ileorectal anastomosis (n=3) or segmental colectomy (n=3). Finally, five patients had permanent stoma. The 13 remaining patients continued to perform irrigations (4.6 per week). The patients' mean KESS score was 18.3+/-8 (normal: <7), and the mean GIQLI score was 98+/-20 (normal: 125). Continence status had no influence on success. CONCLUSION: In our series, MACE was successful in half the patients who were, thus, able to avoid more aggressive approaches. However, when MACE failed, other surgical procedures were often required. PMID- 20299172 TI - Technical aspects of MR diffusion imaging of the body. AB - In diffusion-weighted magnetic resonance imaging (DWI), the intensity of the acquired magnetic resonance signal depends on the self-diffusion of the excited spins, i.e., on the microscopic stochastic Brownian molecular motion. Since the extent and orientation of molecular motion is influenced by the microscopic structure and organization of biological tissues, DWI can depict various pathological changes of organs or tissues. While DWI of the brain can be considered an established technique since the mid-1990s, significantly fewer studies have been published about DWI in body imaging, mainly because of the relatively low robustness of conventional DWI methods in non-neurological applications. Consequently, the image quality in such applications was rather limited. This situation, however, improved considerably in recent years due to better hardware as well as new pulse sequences, and several new applications of DWI (e.g., in the abdominal organs, in musculoskeletal applications, or in whole body protocols) have been described. Unfortunately, DWI of the body is complicated by frequently low signal-to-noise ratios due to shorter transversal (T2) relaxation times and by strong variations of susceptibility. The latter result in severe distortion artifacts when standard echo-planar DWI techniques are applied. Hence, several alternative (non-echo-planar) diffusion-weighting pulse sequence types were proposed and evaluated for DWI applications in the body. In this review article, first the basics of molecular diffusion and of diffusion-weighted MRI are introduced and then several specific MRI techniques, which have been used for DWI of the body, are described. Finally, protocol recommendations for different DWI applications in the body are provided. PMID- 20299173 TI - In contrast to BOLD: signal enhancement by extravascular water protons as an alternative mechanism of endogenous fMRI signal change. AB - Despite the popularity and widespread application of functional magnetic resonance imaging (fMRI) in recent years, the physiological bases of signal change are not yet fully understood. Blood oxygen level-dependant (BOLD) contrast - attributed to local changes in blood flow and oxygenation, and therefore magnetic susceptibility - has become the most prevalent means of functional neuroimaging. However, at short echo times, spin-echo sequences show considerable deviations from the BOLD model, implying a second, non-BOLD component of signal change. This has been dubbed "signal enhancement by extravascular water protons" (SEEP) and is proposed to result from proton-density changes associated with cellular swelling. Given that such changes are independent of magnetic susceptibility, SEEP may offer new and improved opportunities for carrying out fMRI in regions with close proximity to air-tissue and/or bone-tissue interfaces (e.g., the prefrontal cortex and spinal cord), as well as regions close to large blood vessels, which may not be ideally suited for BOLD imaging. However, because of the interdisciplinary nature of the literature, there has yet to be a thorough synthesis, tying together the various and sometimes disparate aspects of SEEP theory. As such, we aim to provide a concise yet comprehensive overview of SEEP, including recent and compelling evidence for its validity, its current applications and its future relevance to the rapidly expanding field of functional neuroimaging. Before presenting the evidence for a non-BOLD component of endogenous functional contrast, and to enable a more critical review for the nonexpert reader, we begin by reviewing the fundamental principles underlying BOLD theory. PMID- 20299174 TI - Perfusion in rat brain at 7 T with arterial spin labeling using FAIR-TrueFISP and QUIPSS. AB - Measurement of perfusion in longitudinal studies allows for the assessment of tissue integrity and the detection of subtle pathologies. In this work, the feasibility of measuring brain perfusion in rats with high spatial resolution using arterial spin labeling is reported. A flow-sensitive alternating recovery sequence, coupled with a balanced gradient fast imaging with steady-state precession readout section was used to minimize ghosting and geometric distortions, while achieving high signal-to-noise ratio. The quantitative imaging of perfusion using a single subtraction method was implemented to address the effects of variable transit delays between the labeling of spins and their arrival at the imaging slice. Studies in six rats at 7 T showed good perfusion contrast with minimal geometric distortion. The measured blood flow values of 152.5+/-6.3 ml/100 g per minute in gray matter and 72.3+/-14.0 ml/100 g per minute in white matter are in good agreement with previously reported values based on autoradiography, considered to be the gold standard. PMID- 20299175 TI - Sober living houses for alcohol and drug dependence: 18-month outcomes. AB - OBJECTIVE: A major challenge facing many individuals attempting to abstain from substances is finding a stable living environment that supports sustained recovery. Sober living houses (SLHs) are alcohol- and drug-free living environments that support abstinence by emphasizing involvement in 12-step groups and social support for recovery. Among a number of advantages, they are financially self-sustaining and residents can stay as long as they wish. Although SLHs can be used as housing referrals after inpatient treatment, while clients attend outpatient treatment, after incarceration, or as an alternative to treatment, they have been understudied and underutilized. METHOD: To describe outcomes of SLH residents, we interviewed 245 individuals within 1week of entering SLHs and at 6-, 12-, and 18-month follow-up. Eighty-nine percent completed at least one follow-up interview. Outcomes included the Addiction Severity Index (ASI), Brief Symptom Inventory (BSI), and measures of alcohol and drug use. Covariates included demographic characteristics, 12-step involvement, and substance use in the social network. RESULTS: Regardless of referral source, improvements were noted on ASI scales (alcohol, drug, and employment), psychiatric severity on the BSI, arrests, and alcohol and drug use. Substance use in the social network predicted nearly all outcome measures. Involvement in 12 step groups predicted fewer arrests and lower alcohol and drug use. CONCLUSION: Residents of SLHs made improvements in a variety of areas. Additional studies should use randomized designs to establish causal effects of SLHs. Results support the importance of key components of the recovery model used by SLHs: (a) involvement in 12-step groups and (b) developing social support systems with fewer alcohol and drug users. PMID- 20299176 TI - Periscope graft to extend distal landing zone in ruptured thoracoabdominal aneurysms with short distal necks. AB - Endovascular aneurysm repair (EVAR) of ruptured thoracoabdominal aortic aneurysms may be compromised or even impossible due to short proximal and/or distal necks or landing zones, respectively. Supra-aortic branches may limit the proximal anchorage and visceral or renal arteries the distal anchorage of endografts. While solutions have been proposed to overcome the problem of a short proximal neck, no technique has been described that solves the problem of a short distal neck. We present the "periscope technique," which allows extension of the distal landing zone and complete endovascular treatment of ruptured thoracoabdominal aneurysms with short distal necks using devices already stocked in most centers performing EVAR procedures. PMID- 20299177 TI - Sustained cognitive benefit 5 years after carotid endarterectomy. AB - OBJECTIVES: This study investigated the long-term effect of carotid endarterectomy (CEA) on cognitive brain function by means of P300 evoked potentials. METHODS: Twenty-five consecutive patients (36% women) with a median age of 68 years underwent CEA with a median degree of stenosis of 90%. Cognitive brain function was objectively measured by means of P300 auditory evoked potentials (peak latencies in milliseconds [ms]) before CEA, at discharge, and at 1 and 5 years. Values were compared with 25 age- and sex-matched healthy individuals. RESULTS: Cognitive P300 evoked potentials were prolonged (ie, impaired) in patients before CEA compared with controls (vertex [Cz], 384 +/- 52 vs 357 +/- 16 ms, P = .020]. At 1 year, P300 evoked potentials were significantly shortened (ie, improved) in patients after CEA compared with baseline values [Cz, 371 +/- 38 vs 384 +/- 52 ms, P = .010]. Furthermore, no difference between patients after CEA and controls was observed [Cz, 371 +/- 38 vs 360 +/- 14 ms, P = .21]. This effect was sustained at 5 years, and P300 evoked potentials continued to be significantly shortened (ie, improved) in patients after CEA compared with baseline values [Cz, 367 +/- 39 vs 384 +/- 52 ms, P = .040]. Continuing, no difference between patients after CEA and controls could be observed [Cz, 367 +/- 39 vs 362 +/- 17 ms, P = .58]. These results could be confirmed in repeated measures analysis of variance for Cz (P = .025) and frontal (Fz) results (P = .018). CONCLUSIONS: CEA improves previously impaired cognitive brain function as shown by P300 measurements similar to normal cognitive brain function of age- and sex-matched healthy individuals. This beneficial effect is sustained up to 5 years after treatment. PMID- 20299178 TI - Quality of life before surgery is a predictive factor for satisfaction among patients undergoing sympathectomy to treat hyperhidrosis. AB - PURPOSE: The objective of this study was to evaluate the postoperative quality of life (QOL) experienced among a group of 1167 patients who underwent video assisted thoracoscopic sympathectomy (VATS) to treat primary hyperhidrosis, as compared with the presurgical QOL. METHODS: Between February 2002 and June 2007, 1167 patients who had undergone VATS were surveyed. The majority had presented with palmar hyperhidrosis (794 patients; 68%), while 340 (29%) had presented with axillary hyperhidrosis. Based on data obtained from the QOL protocol applied to all of the patients preoperatively, the patients were divided into two groups according to the level of their QOL: group 1 consisted of 312 patients (27%) with poor QOL and group 2 of 855 patients (73%) with very poor QOL. The same protocol was applied postoperatively, and five different levels of satisfaction were obtained. The same parameters were evaluated for both the palmar and the axillary hyperhidrosis subgroups. RESULTS: The patients with very poor QOL had much better results in terms of improvement in QOL than did those with poor QOL (P < .05). The same result was observed for both the palmar and axillary hyperhidrosis subgroups (P < .05). CONCLUSION: The worse the preoperative QOL among patients undergoing sympathectomy to treat primary hyperhidrosis is, the better the postoperative improvement in QOL will be. PMID- 20299179 TI - Incidence of and outcomes after misaligned deployment of the talent thoracic stent graft system. AB - OBJECTIVE: Various types of device-specific adverse events can occur during deployment of thoracic stent grafts due to the high flow rate and severe aortic angulation that is often encountered in the thoracic aorta. This study assessed the incidence, etiology, and overall effect of misaligned deployment of the Talent Thoracic Stent Graft (TSG) System. Techniques to predict and avoid this complication are discussed. METHODS: Data collection included pivotal-trial follow-up, direct surveys of centers inside and outside the United States and principal investigators, a targeted literature search, and review of complaint files. Misaligned deployment was considered to occur when the proximal covered or uncovered stent apices of a thoracic stent graft folded back on itself and remained nonparallel to the wall of the aorta after deployment had been completed. RESULTS: Of about 20,305 deployments to date of the Talent TSG, 24 misaligned deployments were identified for an incidence of 0.1%. Nineteen (79%) events occurred during treatment of degenerative aneurysms or penetrating ulcers, four (17%) during treatment of dissections, and the underlying pathology could not be determined for one patient. The misalignment was noted at the proximal end of the stent graft in 15 patients (63%), and the other 9 events (37%) occurred at the graft overlap junction. Two events were treated intraoperatively, with a second overlapping device placed in one patient and a snare used to reposition the proximal stent in another. Adverse clinical events occurred in three patients and included a persistent type I endoleak, continued false lumen perfusion in a patient with dissection, and delayed retrograde type A dissection in a patient undergoing total arch repair. No intraoperative contrast extravasation or computed tomography evidence of perforation was noted. There were no perioperative deaths or cerebrovascular events, with one report of paraplegia among the 24 patients in this series. CONCLUSION: Misaligned deployment is an unusual phenomenon that tends to occur in the context of certain well-defined anatomic conditions in the thoracic aorta. To date, most of these events have not led to significant adverse sequelae. However, careful patient selection, periprocedural imaging, and case planning can help to identify anatomies in which misaligned opening is likely to occur, allowing physicians to avoid this complication. PMID- 20299180 TI - Traumatic arteriovenous fistula 52 years after injury. AB - Untreated traumatic arteriovenous fistulae (AVF) have been associated with aneurysmal dilatation of the involved artery and vein, congestive heart failure, and limb ischemia. Open surgical repair of these lesions can be challenging due to the elevated venous pressure and surrounding inflammation. This case report describes a hybrid open and endovascular approach to treatment of a traumatic AVF in the right groin, presenting with aneurysmal ileo-femoral arteries and veins and pulmonary hypertension. It provides a rare look at the natural history of a traumatic AVF over 50 years following the initial injury. PMID- 20299181 TI - Animal models for the assessment of novel vascular conduits. AB - The development of an ideal small-diameter conduit for use in vascular bypass surgery has yet to be achieved. The ongoing innovation in biomaterial design generates novel conduits that require preclinical assessment in vivo, and a number of animal models have been used for this purpose. This article examines the rationale behind animal models used in the assessment of small-diameter vascular conduits encompassing the commonly used species: baboons, sheep, pigs, dogs, rabbits, and rodents. Studies on the comparative hematology for these species relative to humans are summarized, and the hydrodynamic values for common implant locations are also compared. The large- and small-animal models are then explored, highlighting the characteristics of each that determine their relative utility in the assessment of vascular conduits. Where possible, the performance of expanded polytetrafluoroethylene is given in each animal and in each location to allow direct comparisons between species. New challenges in animal modeling are outlined for the assessment of tissue-engineered graft designs. Finally, recommendations are given for the selection of animal models for the assessment of future vascular conduits. PMID- 20299182 TI - Thrombospondin-1: a proatherosclerotic protein augmented by hyperglycemia. AB - OBJECTIVE: Diabetes is associated with a more aggressive form of atherosclerosis. Thrombospondin-1 (TSP-1), an extracellular matrix protein, is an acute-phase reactant that induces vascular smooth muscle (VSMC) migration and proliferation in areas of vascular injury and is also up-regulated in VSMCs exposed to hyperglycemia. This study tested the hypothesis that hyperglycemia amplifies the expression of genes induced by TSP-1 in VSMCs. METHODS: Human aortic VSMCs were cultured in Dulbecco Modified Eagle's Medium (DMEM) supplemented with 10% fetal bovine serum (FBS) and 1% antibiotics. Cells were used between passages three and five. VSMCs were preincubated in DMEM containing 0.2% FBS with 5 mM glucose (normoglycemia), 25 mM glucose (hyperglycemia), 25 mM mannose (osmotic control), TSP-1 (20 microg/mL), 25 mM glucose + TSP-1 (20 microg/mL), or 25 mM mannose + TSP-1 (20 microg/mL). Total RNA was extracted. Microarray analysis was performed and analyzed by analysis of variance. P < .05 was considered significant. Quantitative real-time polymerase chain reaction (rtPCR) was used to confirm selected up-regulated genes. RESULTS: Microarray analysis revealed: (1) hyperglycemia altered 30 genes; (2) TSP-1 altered 212 genes, of which 8 were altered similarly to VSMCs exposed to 25 mM glucose; (3) TSP-1 up-regulated 10 genes associated with atherosclerosis and 4 others with diabetic vascular disease; (4) hyperglycemia combined with TSP-1 altered expression of 2822 genes. The three genes most up-regulated by TSP-1 in a normoglycemic environment were uridine 5'-diphosphoglucose (UDP-glucose) dehydrogenase (UGDH, 127%), transforming growth factor beta-2 (TGFbeta2, 116%), and hyaluronan synthase 2 (HAS2, 113%). Further, TSP-1 altered the expression of genes in 13 canonical pathways; however, when combined with hyperglycemia, 53 canonical pathways were affected. CONCLUSION: Quantitative rtPCR confirmed that genes in several of these pathways for TSP-1 and hyperglycemia combined with TSP-1 were up-regulated. These findings suggest that TSP-1 may be germane to the progression of atherosclerosis and may have a large effect with concurrent hyperglycemia. PMID- 20299184 TI - Long-term survivorship analysis of the cementless Spotorno femoral component in patients less than 50 years of age. AB - The long-term survival of the cementless Spotorno (CLS) femoral component (Zimmer Inc, Warsaw, USA) was evaluated in a consecutive series of 85 patients (100 hips) less than 50 years of age. The mean follow-up was 12.3 years. Two patients (3 hips) were lost to follow-up, and 3 (4 hips) died. The survival rate of the CLS stem was 96.9% (confidence interval [CI], 93.6%-100%) after 13 years based on revision of the stem for any reason. The survival of the stem with revision for aseptic loosening as the end point was 97.9% (CI, 95.1%-100%) at 13 years. The mean Harris hip score at time of follow-up was 94. The long-term survival of the CLS stem is excellent in patients less than 50 years of age. PMID- 20299185 TI - Treatment choices in autism spectrum disorder: the role of parental illness perceptions. AB - A cross-sectional design was employed. Parents of a child with Autism Spectrum Disorder (ASD) were asked to complete a modified version of the Revised Illness Perception Questionnaire (IPQ-RA) and answer questions about information-seeking activities and treatments used. Internal consistency, construct validity, and factor structure were assessed. Multivariate logistic regressions were performed. Eighty-nine parents having a child with ASD took part in the study. Five subscales of the IPQ-R were replicated. Causes were split into personal, external and hereditary factors. The most highly rated main cause was a genetic cause. Perception of seriousness of the disease was associated with the use of educative methods and unpredictable course of disorder associated with drug use. A higher sense of personal control was associated with reduced use of nutritional or pharmaceutical treatments. Attendance to training programs was associated with higher hereditary beliefs and lower perception of cyclical timeline. The IPQ-RA captures components of representations of autism and provides a reliable mean for exploring illness concept in parents of a child with ASD. Some illness dimensions may prevent parents from having the opportunity to modify their concept of autism. Such measure may be useful for assessing the modification of potentially malleable beliefs with psychoeducational interventions. PMID- 20299186 TI - Effects of physical training and calcium intake on bone mineral density of students with mental retardation. AB - The purpose of this study was to investigate the effects of physical training and calcium intake on bone mineral density (BMD) of students with mental retardation. Forty mentally retarded boys (age 7-10 years old) were randomly assigned to four groups (no differences in age, BMD, calcium intake and physical activity): training groups with or without calcium supplementation (Tr+Ca+ and Tr+Ca-) and nontraining groups with or without calcium supplementation (Tr-Ca+ and Tr-Ca-). The intervention involved 45 min of physical training performed 3 sessions a week and/or the addition of dietary calcium-rich food using enriched cow milk with vitamin D containing 230 mg calcium per serving, over 6 months. Paired-samples t test and ANOVA analysis was used to determine the main and combined effects of training and calcium on BMD. All groups showed greater femoral neck BMD after 6 months. The increase in femoral neck BMD in the Tr+Ca+ group was 10% greater than increase in the Tr+Ca- group (not significant). Apparently, the effect of training was greater than calcium intake because the Tr+Ca- group achieved 4% greater BMD than Tr-Ca+ group (not significant). In this study, both training groups had greater BMD than the control group (Tr-Ca-) (P<0.05). In these participants with inadequate calcium intakes, additional exercise and calcium supplementation resulted in a 6-20% greater increase in BMD than controls at the loaded site (femoral neck). These results help to provide more evidence for public health organizations to deal with both exercise and nutrition issues in children for the achievement of peak BMD. PMID- 20299187 TI - Inlay-onlay grafting for three-dimensional reconstruction of the posterior atrophic maxilla with mandibular bone. AB - This prospective study describes and evaluates a surgical approach for 3D reconstruction of the posterior maxilla with autogenous mandibular bone in 16 patients (mean age 51 years). Bone blocks were harvested from the mandible and used as lateral or vertical block grafts (onlay); they were also partially milled and used for sinus elevation (inlay). In 4 cases, anorganic bovine bone was added at the periphery of the blocks. 4 months after grafting, implants were placed in a second operation and loaded after 12 weeks. Lateral and vertical augmentations were measured immediately after grafting and at re-entry for implant placement. Mean lateral augmentation performed was 5.5mm, reduced to 4.3mm (p<0.01) after 4 months' healing. Mean vertical augmentation was 3.2mm, reduced to 2.1mm (p<0.01) after healing. The amounts of lateral and vertical graft resorption were similar (1.2mm vs. 1.1mm) but were different when compared with the original graft (22% vs. 34%). 49 implants were placed 4 months after grafting. Implant parameters were evaluated after 32-48 months follow up and demonstrated 100% survival rates. The use of mandibular bone grafts for 3D augmentation of the posterior maxilla has shown good results and minor complications. PMID- 20299188 TI - Clomipramine increases the incidence and duration of spike-wave discharges in freely moving WAG/Rij rats. AB - PURPOSE: The noradrenergic and serotonergic system may have a role in modulation of absence seizures. We investigated whether the single injection of monoamine reuptake inhibitor clomipramine has an acute effect on spike-wave discharge (SWD) activity in Wistar Albino Glaxo/Rijswijk (WAG/Rij) rats. METHODS: We injected a single dose of 20 or 50 mg/kg clomipramine intraperitoneally into WAG/Rij rats and measured the incidence and duration of SWD episodes for 4h after injection. The changes in SWDs were compared to the preceding 5-day average control level. RESULTS: The 20 mg/kg clomipramine significantly increased the incidence of SWDs in the first measured hour while the 50 mg/kg dose significantly increased the incidence and duration of SWDs in the whole measured 4-h period. CONCLUSIONS: Clomipramine, by acutely elevating synaptic monoamine levels, could exacerbate absence seizures. PMID- 20299189 TI - Eslicarbazepine acetate as adjunctive therapy in adult patients with partial epilepsy. AB - OBJECTIVE: To investigate the efficacy and safety of once-daily eslicarbazepine acetate (ESL) when used as add-on treatment in adults with > or = 4 partial-onset seizures per 4-week despite treatment with 1 to 3 antiepileptic drugs (AEDs). METHODS: This double-blind, parallel-group, multicenter study consisted of an 8 week observational baseline period, after which patients were randomized to placebo (n=100) or once-daily ESL 400 mg (n=96), 800 mg (n=101), or 1200 mg (n=98). Patients then entered a 14-week double-blind treatment phase. All patients started on their full maintenance dose except for those in the ESL 1200 mg group who received once-daily ESL 800 mg for 2 weeks before reaching their full maintenance dose. RESULTS: Seizure frequency per 4-week (primary endpoint) over the 14-week double-blind treatment period was significantly lower than placebo in the ESL 800 mg and 1200 mg (p<0.001) groups. Responder rate (> or = 50% reduction in seizure frequency) was 13.0% (placebo), 16.7% (400 mg), 40.0% (800 mg, p<0.001), and 37.1% (1200 mg, p<0.001). Median relative reduction in seizure frequency was 0.8% (placebo), 18.7% (400 mg), 32.6% (800 mg, p<0.001), and 32.8% (1200 mg). Discontinuation rates due to adverse events (AEs) were 3.0% (placebo), 12.5% (400 mg), 18.8% (800 mg), and 26.5% (1200 mg). The most common (>5%) AEs in any group were dizziness, somnolence, headache, nausea, diplopia, abnormal coordination, vomiting, blurred vision, and fatigue. The majority of AEs were of mild or moderate severity. CONCLUSIONS: Treatment with once-daily eslicarbazepine acetate 800 mg and 1200 mg was more effective than placebo and generally well tolerated in patients with partial-onset seizures refractory to treatment with 1 to 3 concomitant AEDs. PMID- 20299190 TI - Phosphodiesterase signaling system is disrupted in the cerebella of subjects with schizophrenia, bipolar disorder, and major depression. PMID- 20299191 TI - Comparison of the efficacy and impact on cognition of glycopyrrolate and biperiden for clozapine-induced sialorrhea in schizophrenic patients: a randomized, double-blind, crossover study. AB - BACKGROUND: Clozapine-induced sialorrhea (CIS) is a subjective distressing adverse effect and occurs in 31%-57% of schizophrenic patients receiving clozapine therapy. Current pharmacotherapy on CIS has focused on anticholinergic agents, even though they may impair cognitive function. Previous case reports have suggested the benefit of glycopyrrolate or biperiden in treating this condition, but no randomized controlled trial has provided evidence. The objective of our study was to evaluate the efficacy and impact on cognition of glycopyrrolate and biperiden treatments for schizophrenic patients suffering from CIS. METHODS: Patients who satisfied the inclusion criteria entered a 12-week, randomized, double-blind, crossover, fixed-dose trial. The study consisted of two 4-week crossover phases, which were separated by a 4-week washout period. Sialorrhea and global cognitive function were assessed by using a Drooling Rating Scale (DRS) and the Mini Mental State Examination (MMSE), respectively. RESULTS: Throughout the study, patients treated with glycopyrrolate or biperiden had significantly reduced DRS scores. Moreover, the DRS scores were significantly lower with glycopyrrolate treatment than with biperiden. In other respects, there were no significant differences in MMSE scores in patients treated with glycopyrrolate. However, we found a significant reduction in MMSE scores in patients treated with biperiden. CONCLUSION: We provide evidence, for the first time, of the efficacy of glycopyrrolate and biperiden in the treatment of CIS. Furthermore, glycopyrrolate displays less impact on cognitive function. Consequently, glycopyrrolate can become a valid option for treating CIS. Observations from our study serve as a springboard for additional large-scale prospective trials. PMID- 20299192 TI - A self-organized 3-diethylaminopropyl-bearing glycol chitosan nanogel for tumor acidic pH targeting: in vitro evaluation. AB - In this study, a novel pH-responsive nanogel composed of glycol chitosan (GCS) grafted with functional 3-diethylaminopropyl (DEAP) groups (denoted as GCS-g-DEAP hereafter) was fabricated. The GCS-g-DEAP was designed to have a self-assembled arrangement consisting of hydrophilic block (GCS) and hydrophobic block (DEAP) at physiological pH. As the pH decreased to tumor extracellular pH (pH(e)), the nanogel was destabilized due to the protonation of DEAP. The pH-responsive property of the nanogel at tumor extracellular pH (pH(e)) was characterized in drug-release kinetic studies. The release of doxorubicin (DOX) from DOX-loaded nanogels was significantly accelerated at lower pH values, which allowed for increased DOX uptake by non-small lung carcinoma A546 cells under a slightly acidic pH condition, as in tumor pH(e). PMID- 20299193 TI - A kinetic study of silver nanoparticles formation from paracetamol and silver(I) in aqueous and micellar media. AB - UV-vis spectrophotometeric, transmission electron microscopy (TEM) and viscometric techniques were used for the formation, characterization and kinetics of silver sol formation using silver nitrate as source of silver, paracetamol as reducing agent and cetyltrimethylammonium bromide (CTAB) as the stabilizer in absence and presence of poly(vinyl alcohol) (PVA). The sigmoidal curve of absorbance versus the reaction time suggests an autocatalytic reaction path. Transmission electron microscopy (TEM) results show that the silver nanoparticles are all spherical, highly dispersed and aggregated in aqueous solution. In the formation of silver nanoparticles, alkaline solution is required. The presence of PVA inhibits the rate of silver nanoparticles formation. Effects of [Ag(+)], [paracetamol], [CTAB], [NaOH] and [PVA] on the silver sol formation rate were analyzed. PMID- 20299194 TI - Rational antibody-based HIV-1 vaccine design: current approaches and future directions. AB - Many antiviral vaccines elicit neutralizing antibodies as a correlate of protection. For HIV, given the huge variability of the virus, it is widely believed that the induction of a broadly neutralizing antibody (bNAb) response will be crucial in a successful vaccine against the virus. Unfortunately, despite many efforts, the development of an immunogen that elicits bNAbs remains elusive. However, recent structural studies of HIV-1 Env proteins, generation of novel bNAbs, maturation of technologies for the isolation of further antibodies, insights into the requirements for antibody-mediated protection, and novel vaccination approaches are providing grounds for renewed optimism. PMID- 20299195 TI - Awakening lineage potential by Ikaros-mediated transcriptional priming. AB - Bioinformatic studies on a revised hierarchy of hematopoietic progenitors have provided a genome-wide view of lineage-affiliated transcriptional programs directing early hematopoiesis. Unexpectedly, lymphoid, myeloid, and erythroid gene expression programs were primed with similar frequency at the multipotent progenitor stage indicating a stochastic nature to this process. Multilineage transcriptional priming is quickly resolved upon erythroid lineage restriction with both lymphoid and myeloid transcriptional programs rapidly extinguished. However, expression of lymphoid and myeloid factors remains active past nominal lymphoid and myeloid lineage restrictions, revealing a common genetic network utilized by both pathways. Priming and resolution of multilineage potential is dependent on the activity of the DNA binding factor Ikaros. Ikaros primes the lymphoid transcriptional program in the HSC and represses the stem cell and other disparate transcriptional programs downstream of the HSC. Loss of Ikaros removes the lymphoid leg of the immune system and may confer aberrant self-renewing properties to myeloid progenitors. PMID- 20299196 TI - Relationship of body composition and C-reactive protein with pulmonary function. AB - OBJECTIVES: It has been observed that restrictive pulmonary function is associated with obesity and C-reactive protein (CRP), an indicator for systemic inflammation. However, the interrelationship among body composition, CRP, and restrictive pulmonary function has been poorly understood. This study focused on the combined effects of body composition and CRP on restrictive pulmonary function. METHODS: We performed a cross-sectional study to examine the association of body composition and CRP with restrictive pulmonary function in 12,787 subjects (7083 men, 5704 women; ages 20-75 yr). We evaluated body composition and CRP as a categorical variable (non-obesity, percentage body fat 75 percentile; low-inflammation, CRP 75 percentile) and constructed 4 groups, which were non-overlapping (reference, inflammatory, obese, obese and inflammatory). The odds ratios (ORs) and 95% confidence intervals (CIs) for restrictive pulmonary function were calculated across all 4 groups. RESULTS: The adjusted ORs (95% CIs) for restrictive pulmonary function according to the 4 groups were 1.00(reference), 1.19(0.93-1.52), 2.01(1.53-2.64) and 3.51(2.60-4.74) in men and 1.00 (reference), 1.26 (0.96-1.69), 1.02 (0.58-1.81), and 3.32 (2.09 5.27) in women after adjusting for confounding variables. Interaction was found between the body fat percentage and CRP in women only (P < 0.05). CONCLUSIONS: In summary, the coexistence of high fat accumulation and systemic subclinical inflammation is associated with restrictive pulmonary function. PMID- 20299198 TI - Preparation of mixed-templates molecularly imprinted polymers and investigation of the recognition ability for tetracycline antibiotics. AB - We developed in the present study a set of molecularly imprinted polymers (MIPs) by precipitation polymerization, using four members of tetracycline antibiotics (TCs) as templates (Oxytetracycline, Tetracycline, Chlortetracycline and Doxycycline). Then, based on the imprinting effect of different MIPs (TCs), Oxytetracycline and Chlortetracycline were chosen as mixed-templates to synthesize high selective MIPs for recognition of a family of analytes. And the characterization of obtained MIPs was analyzed by FESEM analysis, Brunauer-Emmett Teller (BET) method, polymer size analysis, and determination of swelling ratio and COOH capacity. It was shown that the optimal imprinting factors of TCs on mixed-templates MIPs were more than 6.0 and the maximum binding amount of TCs were about 27 micromol g(-1) (Oxytetracycline), 35 micromol g(-1) (Tetracycline), 35 micromol g(-1) (Chlortetracycline) and 39 micromol g(-1) (Doxycycline), respectively. Finally, the mixed-templates MIPs were shown to be promising for on line solid-phase extraction-HPLC-UV determination of trace TCs in foodstuffs. With a sample loading volume of 10 mL, the enhancement factors were in the range of 159-410. PMID- 20299199 TI - A sensitive ligase-based ATP electrochemical assay using molecular beacon-like DNA. AB - A sensitive and selective ligase-based signal-on electrochemical sensing method for adenosine-5'-triphosphate (ATP) detection had been developed using molecular beacon (MB)-like DNA. In this method, the biotin-tagged MB-like DNA was self assembled onto a gold electrode to form a stem-loop structure by means of facile gold-thiol chemistry, which resulted in blockage of electronic transmission. It was eT OFF state. In the presence of ATP, two nucleotide fragments which were complementary to the loop of the MB-like DNA could be ligated by the ATP dependent T4 DNA ligase. Hybridization of the ligated DNA with the MB-like DNA induced a significant conformational change in this surface-confined DNA structure, which in turn released the biotin from the surface allowing free exchange of electrons with the electrode generating a measurable electrochemical signal (eT ON). The resulting change in electron transfer efficiency was readily measured by differential pulse voltammetry at target ATP concentrations as low as 0.05 nM and with linear response range from 0.1 to 1000 nM. Moreover, it was also able to discriminate ATP from its analogues. The proposed method had been successfully applied to the determination of ATP in the Escherichia coli O157:H7 extracts of water samples, and the linear response was found between the concentrations of 10(3) and 10(7) cfu/mL. PMID- 20299200 TI - A microbial fuel cell as power supply for implantable medical devices. AB - This study seeks a new way to provide lasting and secure power for implantable medical devices (IMDs) using a microbial fuel cell (MFC) which was proposed to be placed in human large intestine and could utilize intestinal contents and microorganisms to generate electricity. Based on the anatomic structure and inner environmental conditions of large intestine, transverse colon was chosen to be the appropriate location for the implantation of MFC. The performance of the MFC which simulated the environmental features of transverse colon by controlling dissolved oxygen (DO) and pH and was inoculated with simulated intestinal fluid (SIF) was investigated. Stable power generation of MFC was obtained after two months operation with open circuit voltage (OCV) of 552.2 mV, maximum power density of 73.3 mW/m(2), and average voltage output of 308 mV (with external resistance of 500 Omega). Moreover, the changes of environmental conditions in the chambers of MFC did not have a significant impact on human body based on the analysis of pH and DO values. Further studies on internal resistance and power density showed that the MFC could generate power of 7-10 mW according to the size of intestinal surface area, which was enough for IMDs. These results suggested that MFCs located in large intestine could be a promising power source for IMDs. PMID- 20299197 TI - Chromatin as a potential carrier of heritable information. AB - Organisms with the same genome can inherit information in addition to that encoded in the DNA sequence-this is known as epigenetic inheritance. Epigenetic inheritance is responsible for many of the phenotypic differences between different cell types in multicellular organisms. Work by many investigators over the past decades has suggested that a great deal of epigenetic information might be carried in the pattern of post-translational modifications of the histone proteins, although this is not as well established as many believe. For example, it is unclear whether and how the histones, which are displaced from the chromosome during passage of the replication fork and are often exchanged from the DNA template at other times, carry information from one cellular generation to the next. Here, we briefly review the evidence that some chromatin states are indeed heritable, and then focus on the mechanistic challenges that remain in order to understand how this inheritance can be achieved. PMID- 20299201 TI - Graphene oxide arrays for detecting specific DNA hybridization by fluorescence resonance energy transfer. AB - The unique properties of graphene oxides (GO) such as water dispersibility, versatile surface modification, and photoluminescence make them suitable for biological applications. In this study, we explored the use of GO sheets as a novel DNA biosensor by applying the GO in an array format to recognize specific DNA-DNA hybridization interaction. When the probe DNA linked to the surface of GO by using carbodiimide chemistry is hybridized with a gold nanoparticle (Au NP) labeled complementary DNA strand, the fluorescence emission intensity of the GO array is drastically reduced. TEM data reveal that the Au NPs are dispersed on the GO surface, particularly at edges and folded structures upon hybridization with a density of approximately 80 Au NPs per microm(2). This leads to ca. 87% fluorescence quenching as a consequence of fluorescence energy transfer between Au NPs and the GO sheets. These results suggest that the GO nanomaterials, which are readily synthesized on a large scale from a cheap graphite source, could have a wide range of bioapplications in the fields of biosensors, molecular imaging and nanobiotechnology. PMID- 20299202 TI - Functionalized single-walled carbon nanohorns for electrochemical biosensing. AB - Single-walled carbon nanohorns (SWNHs), distinguished by their high purity and distinct structure, were noncovalently functionalized with poly(sodium 4 styrenesulfonate). The functionalized SWNHs were characterized by scanning electron microscopy, atomic force microscopy, ultraviolet-visible spectroscopy, Fourier transform infrared spectroscopy, Raman spectroscopy, and thermogravimetry. Heme protein myoglobin was adsorbed onto surface of functionalized SWNHs to prepare electrochemical biosensor. Surface assembly process and direct electrochemistry of immobilized myoglobin were investigated by electrochemical impedance spectroscopy and cyclic voltammetry, respectively. The proposed biosensor exhibited good electrocatalysis to the reduction of hydrogen peroxide. The response was linear over the range 3-350 microM with a detection limit of 0.5 microM. Good reproducibility and stability of the biosensor were obtained toward hydrogen peroxide detection. PMID- 20299203 TI - Advances in subtyping methods of foodborne disease pathogens. AB - Current subtyping methods for the detection of foodborne disease outbreaks have limitations that reduce their use by public health laboratories. Recent advances in subtyping of foodborne disease pathogens utilize techniques that identify nucleic acid polymorphisms. Recent methods of nucleic acid characterization such as microarrays and mass spectrometry (MS) may provide improvements such as increasing speed and data portability while decreasing labor compared to current methods. This article discusses multiple-locus variable-number tandem-repeat analysis, single-nucleotide polymorphisms, nucleic acid sequencing, whole genome sequencing, variable absent or present loci, microarrays and MS as potential subtyping methods to enhance our ability to detect foodborne disease outbreaks. PMID- 20299205 TI - Texture coding in the whisker system. AB - The whisker somatosensory system in awake, behaving rodents is a powerful model for studying neurobiology of sensation, from molecules to circuits to behavior. Recent studies reveal how key tactile features are detected in awake animals and encoded by spike trains in somatosensory cortex (S1). Here we summarize progress on detection of surface texture (roughness). Texture appears to be inferred from the statistics of complex, irregular whisker micromotion on surfaces, specifically by mean speed or by patterns of discrete, high-velocity whisker slips. These are encoded in S1 by mean firing rate and by sparse, synchronous, slip-evoked spike volleys, respectively. An alternative model of place coding for texture based on differential whisker resonance is less well supported, but is not ruled out. PMID- 20299204 TI - Re-valuing the amygdala. AB - Recent advances indicate that the amygdala represents valence: a general appetitive/aversive affective characteristic that bears similarity to the neuroeconomic concept of value. Neurophysiological studies show that individual amygdala neurons respond differentially to a range of stimuli with positive or negative affective significance. Meanwhile, increasingly specific lesion/inactivation studies reveal that the amygdala is necessary for processes- for example, fear extinction and reinforcer devaluation--that involve updating representations of value. Furthermore, recent neuroimaging studies suggest that the human amygdala mediates performance on many reward-based decision-making tasks. The encoding of affective significance by the amygdala might be best described as a representation of state value-a representation that is useful for coordinating physiological, behavioral, and cognitive responses in an affective/emotional context. PMID- 20299206 TI - Variation in 'standard care' for breast cancer across Europe: a EUROCARE-3 high resolution study. AB - On a population-based sample of 13,500 European breast cancer patients mostly diagnosed in 1996-1998 and archived by 26 cancer registries, we used logistic regression to estimate odds of conservative surgery plus radiotherapy (BCS+RT) versus other surgery, in T1N0M0 cases by country, adjusted for age and tumour size. We also examined: BCS+RT in relation to total national expenditure on health (TNEH); chemotherapy use in N+ patients; tamoxifen use in oestrogen positive patients; and whether 10 nodes were examined in lymphadenectomies. Stage, diagnostic examinations and treatments were obtained from clinical records. T1N0M0 cases were 33.0% of the total. 55.0% of T1N0M0 received BCS+RT, range 9.0% (Estonia) to 78.0% (France). Compared to France, odds of BCS+RT were lower in all other countries, even after adjusting for covariates. Women of 70-99 years had 67% lower odds of BCS+RT than women of 15-39 years. BCS+RT was 20% in low TNEH, 58% in medium TNEH, and 64% in high TNEH countries. Chemotherapy was given to 63.0% of N+ and 90.7% of premenopausal N+ (15-49 years), with marked variation by country, mainly in post-menopause (50-99 years). Hormonal therapy was given to 55.5% of oestrogen-positive cases, 44.6% at 15-49 years and 58.8% at 50-99 years; with marked variation across countries especially in premenopause. The variation in breast cancer care across Europe prior to the development of European guidelines was striking; older women received BCS+RT much less than younger women; and adherence to 'standard care' varied even among countries with medium/high TNEH, suggesting sub-optimal resource allocation. PMID- 20299208 TI - Co-pyrolysis characteristics of sawdust and coal blend in TGA and a fixed bed reactor. AB - Co-pyrolysis characteristics of sawdust and coal blend were determined in TGA and a fixed bed reactor. The yield and conversion of co-pyrolysis of sawdust and coal blend based on volatile matters are higher than those of the sum of sawdust and coal individually. Form TGA experiments, weight loss rate of sawdust and coal blend increases above 400 degrees C and additional weight loss was observed at 700 degrees C. In a fixed bed at isothermal condition, the synergy to produce more volatiles is appeared at 500-700 degrees C, and the maximum synergy exhibits with a sawdust blending ratio of 0.6 at 600 degrees C. The gas product yields remarkably increase at lower temperature range by reducing tar yield. The CO yield increases up to 26% at 400 degrees C and CH(4) yield increases up to 62% at 600 degrees C compared with the calculated value from the additive model. PMID- 20299207 TI - Evaluation of the catalytic properties of Burkholderia cepacia lipase immobilized on non-commercial matrices to be used in biodiesel synthesis from different feedstocks. AB - The objective of this work was to produce an immobilized form of lipase from Burkholderia cepacia (lipase PS) with advantageous catalytic properties and stability to be used in the ethanolysis of different feedstocks, mainly babassu oil and tallow beef. For this purpose lipase PS was immobilized on two different non-commercial matrices, such as inorganic matrix (niobium oxide, Nb(2)O(5)) and a hybrid matrix (polysiloxane-polyvinyl alcohol, SiO(2)-PVA) by covalent binding. The properties of free and immobilized enzymes were searched and compared. The best performance regarding all the analyzed parameters (biochemical properties, kinetic constants and thermal stability) were obtained when the lipase was immobilized on SiO(2)-PVA. The superiority of this immobilized system was also confirmed in the transesterification of both feedstocks, attained higher yields and productivities. PMID- 20299209 TI - Methanogenesis control by employing various environmental stress conditions in two-chambered microbial fuel cells. AB - This study examines methanogen activity in microbial fuel cells when exposed to various environmental stresses, such as oxygen, low pH, low temperature, inhibitor (2-bromoethanesulfonate (BES)), and variations in external resistance. Controlling methanogenesis resulted in an increase in Coulombic efficiency (CE) because it was a major cause of electron loss. Methane was mainly produced from aceticlastic methanogenesis, rather than by syntrophic acetate oxidation, with Methanosarcinaceae being the primary contributor. Lowering the resistance from 600 to 50 Omega reduced the methanogenic electron loss by 24%; however, changing the temperature or pH level had little effect. A BES injection was the most potent strategy for the selective inhibition of methanogens without damaging exoelectrogens. The addition of 0.1-0.27 mM BES increased the CE from 35% to 70%. Oxygen stress successfully inhibited methanogens, while slightly suppressing the exoelectrogens, and is believed to be a practical option due to its low operating cost. PMID- 20299210 TI - Variability of bulk density of distillers dried grains with solubles (DDGS) during gravity-driven discharge. AB - Loading railcars with consistent tonnage has immense cost implications for the shipping of distillers' dried grains with soluble (DDGS) product. Therefore, this study was designed to investigate the bulk density variability of DDGS during filling of railcar hoppers. An apparatus was developed similar to a spinning riffler sampler in order to simulate the filling of railcars at an ethanol plant. There was significant difference (P<0.05) between the initial and final measures of bulk density and particle size as the hoppers were emptied in both mass and funnel flow patterns. Particle segregation that takes place during filling of hoppers contributed to the bulk density variation and was explained by particle size variation. This phenomenon is most likely the same throughout the industry and an appropriate sampling procedure should be adopted for measuring the bulk density of DDGS stored silos or transported in railcar hoppers. PMID- 20299211 TI - Enhancement of anti-complementary and radical scavenging activities in the submerged culture of Cordyceps sinensis by addition of citrus peel. AB - To investigate the optimal conditions for the production of Cordyceps sinensis by the submerged culture method, glucosamine and exopolysaccharide (EPS) productivities were determined in culture broth containing different carbon sources, principally rice bran and citrus peel. An optimal medium composition (1.5% rice bran, 0.5% molasses, 3% CSL, 0.1% KH(2)PO(4), and 0.05% MgSO(4)) and the optimal condition (25 degrees C and 5-6 d culture time) for high EPS productivity with potent immune-stimulating activities were obtained. The addition of citrus peel to the culture of C. sinensis under the optimized conditions improved EPS productivity and glucosamine content. Furthermore, anti complementary activity was higher (58.0-80.8%) using citrus peel as compared to no addition of citrus peel (48.2-68.7%). Antioxidant activity (AEAC value) of the citrus peel culture was high (284.3-384.6 mg/100g) compared to that of the culture without citrus peel (142.8-219.5mg/100g), indicating that the citrus peel helped enhance the anti-complementary and antioxidant activities of C. sinensis. PMID- 20299212 TI - Comparison of single-step and two-step purified coagulants from Moringa oleifera seed for turbidity and DOC removal. AB - The coagulant proteins from Moringa oleifera purified with single-step and two step ion-exchange processes were used for the coagulation of surface water from Meuse river in The Netherlands. The performances of the two purified coagulants and the crude extract were assessed in terms of turbidity and DOC removal. The results indicated that the optimum dosage of the single-step purified coagulant was more than two times higher compared to the two-step purified coagulant in terms of turbidity removal. And the residual DOC in the two-step purified coagulant was lower than in single-step purified coagulant or crude extract. PMID- 20299213 TI - [(11)C]Dimebon, radiosynthesis and lipophilicity of a new potential PET agent for imaging of Alzheimer's disease and Huntington's disease. AB - [(11)C]Dimebon (2-[(11)C]methyl-8-methyl-5-(2-(6-methylpyridin-3-yl)ethyl) 2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole), a new potential PET agent for imaging of Alzheimer's disease and Huntington's disease, was prepared by N [(11)C]methylation of desmethyl-Domebon precursor with [(11)C]CH(3)OTf and purified with a semi-preparative HPLC method in 30-40% decay corrected radiochemical yield and 222-296GBq/mumol specific activity at EOB. The measured lipophilicity coefficient (LogP) value of [(11)C]Dimebon was 2.53. PMID- 20299215 TI - Identification and hit-to-lead exploration of a novel series of histamine H4 receptor inverse agonists. AB - The identification and hit-to-lead exploration of a novel, potent and selective series of histamine H(4) receptor inverse agonists is described. The initial hit, 3A (IC(50) 19 nM) was identified by means of a ligand-based virtual screening approach. Subsequent medicinal chemistry exploration yielded 18I which possessed increased potency (R-enantiomer IC(50) 1 nM) as well as enhanced microsomal stability. PMID- 20299214 TI - (S)-3-(4-(2-(5-Methyl-2-phenyloxazol-4-yl)ethoxy)phenyl)-2-(piperazin-1-yl) propanoic acid compounds: synthesis and biological evaluation of dual PPARalpha/gamma agonists. AB - A series of novel, potent PPARalpha/gamma dual agonists were synthesized and appraised. The most potent analogue, compound 2b demonstrated EC(50) value of 0.012+/-0.002 and 0.032+/-0.01 microM, respectively, for hPPARalpha and hPPARgamma in transactivation assay. Additionally, compound 2b demonstrated good glucose and lipid lowering effect in genetic diabetic (db/db) mice. PMID- 20299216 TI - Benzyl prolinate derivatives as novel selective KCC2 blockers. AB - The discovery and optimization of a novel class of selective submicromolar KCC2 blockers is described. Details of synthesis and SAR are given together with ADME properties of selected compounds. A methylsulfone residue on the R(1) phenyl group improved the overall general profile of these prolinate derivatives. PMID- 20299217 TI - Chemopreventive activities of etodolac and oxyphenbutazone against mouse skin carcinogenesis. AB - Previous cancer chemoprevention studies have demonstrated that the non-steroidal anti-inflammatory drugs (NSAIDs) can be effective in suppressing the development of various human malignancies. Recently we identified the possible anti-tumor promoting potentials of 14 new NSAIDs in the Epstein-Barr virus early antigen activation assay induced by 12-O-tetradecanoylphorbol-13-acetate (TPA). In this study we report the inhibition of 7,12-dimethylbenz (a) anthracene (DMBA) induced two-stage mouse skin carcinogenesis by etodolac (ETD), one of the most potent NSAIDs identified in our in vitro cancer chemopreventive screening of this group of drugs. Topical administration of ETD at a very low dose of 85 nmol showed a significant decrease in both tumor incidence and burden. This effect is also accompanied by a delay in the tumor latency period. Since ETD showed potent chemopreventive activity in both in vitro and in vivo studies, it warrants prompt consideration for trial in humans as a potential cancer chemopreventive agent. We also investigated oxyphenbutazone (OPB) another commonly used NSAID for its cancer chemopreventive effect on peroxynitrite (PN) induced-TPA promoted skin tumors in the mouse. Following tumor initiation with 390 nmol of PN, the skin tumor promotion with 1.7 nmol of TPA was significantly inhibited by oral administration of 0.0025% OPB. The results demonstrate that OPB is a potent cancer chemopreventive agent in the highly sensitive in vivo mouse test model we used. PMID- 20299218 TI - Identification of potent, highly constrained CGRP receptor antagonists. AB - A novel series of potent CGRP receptor antagonists containing a central quinoline ring constraint was identified. The combination of the quinoline constraint with a tricyclic benzimidazolinone left hand fragment produced an analog with picomolar potency (14, CGRP K(i)=23 pM). Further optimization of the tricycle produced a CGRP receptor antagonist that exhibited subnanomolar potency (19, CGRP K(i)=0.52 nM) and displayed a good pharmacokinetic profile in three preclinical species. PMID- 20299219 TI - Carbonic anhydrase inhibitors. The beta-carbonic anhydrases from the fungal pathogens Cryptococcus neoformans and Candida albicans are strongly inhibited by substituted-phenyl-1H-indole-5-sulfonamides. AB - A series of 2-(hydrazinocarbonyl)-3-substituted-phenyl-1H-indole-5-sulfonamides and 1-({[5-(aminosulfonyl)-3-phenyl-1H-indol-2-yl]carbonyl}amino)-2,4,6 trimethylpyridinium perchlorates possessing various 2-, 3- or 4-substituted phenyl groups with methyl-, halogeno- and methoxy-functionalities, as well as the perfluorophenyl moiety, have been evaluated as inhibitors of the beta-carbonic anhydrases (CAs, EC 4.2.1.1) from the pathogenic fungi Cryptococcus neoformans (Can2) and Candida albicans (CaNce103). Both enzymes were potently inhibited by these sulfonamides, K(I)s in the range of 4.4-118 nM against Can2, and of 5.1-128 against CaNce103, respectively. Minor structural changes in the 3-substituted phenyl moiety contribute significantly to the inhibitory activity. Some of the investigated sulfonamides showed promising selectivity ratios for inhibiting Can2 over the host, human enzymes CA I and II. PMID- 20299220 TI - 4,7-Dichloro benzothien-2-yl sulfonylaminomethyl boronic acid: first boronic acid derived beta-lactamase inhibitor with class A, C, and D activity. AB - 4,7-Dichloro-1-benzothien-2-yl sulfonylaminomethyl boronic acid (DSABA, Compound I) was discovered as the first boronic acid-based class D beta-lactamase inhibitor. It exhibited an IC(50) of 5.6 microM against OXA-40. The compound also inhibited class A and C beta-lactamases with sub to low microM IC(50), and synergized with imipenem against Acinetobacter baumannii. PMID- 20299222 TI - Solutions for representing the whole-body centre of mass in side cutting manoeuvres based on data that is typically available for lower limb kinematics. AB - While studying detailed lower limb mechanics of dynamic sports manoeuvres like side cutting it is often desirable but practically difficult to directly measure velocity profiles of the whole-body centre of mass (CoM). In the current study, representations of CoM, either based on a single marker placed on the pelvis or thorax, or based on segment kinematics of lower limbs with or without inclusion of trunk, were evaluated against whole-body CoM representation. Using the 95% limits of agreement method for comparison of two methods, strongest agreement was found between velocity of whole-body CoM and CoM representation based on lower limbs with the addition of the trunk. The CoM representation based on lower limbs only showed weaker agreement, but this representation was still markedly superior to single marker representations. PMID- 20299223 TI - Symmetrical kinematic changes in highly functioning older patients post-stroke during obstacle-crossing. AB - With the advances in stroke care, the number of high-functioning patients after stroke is increasing. However, existing clinical tools may not be sensitive enough to identify the residual deficits in these patients. The current study aimed to investigate the control of the pelvis, and the joints and end-point of the lower limbs in high-functioning older patients post-stroke during obstacle crossing using motion analysis techniques. Twenty-four high-functioning older patients following unilateral stroke and fifteen healthy controls walked and crossed obstacles of three different heights. End-point variables (leading toe clearance and trailing toe-obstacle distance) and crossing pelvic and joint angles were obtained for both limbs during leading limb crossing. Whether leading with the contralesional or ipsilesional limb, the stroke group exhibited significantly different joint kinematics from the controls mainly in the frontal and transverse planes, with greater leading toe-clearance, trailing toe-obstacle distance, and posterior pelvic tilt. None of the end-point and joint variables were significantly different between limbs. High-functioning patients post-stroke appeared to have acquired a specific symmetric kinematic strategy with increased leading toe-clearance during obstacle-crossing, most likely in order to prevent tripping. This symmetric strategy, possibly a consequence of brain reorganization, may help in performing functional activities during which symmetric performance between the contralesional and ipsilesional sides is required. Obstacle-crossing training with both limbs leading alternately may be helpful for the development of this symmetric strategy. It is suggested that computerized motion analysis of obstacle-crossing can be a sensitive assessment tool for distinguishing the motor performance between normal and high-functioning patients post-stroke. PMID- 20299221 TI - Single-molecule imaging brings Rad51 nucleoprotein filaments into focus. AB - The Rad51 protein is essential for DNA repair by homologous recombination. After DNA damage, Rad51 localizes to nuclear foci that represent sites of DNA repair in vivo. In vitro, Rad51 self-assembles on single- or double-stranded DNA to form a nucleoprotein filament. Recently, the merging of innovative single-molecule techniques with ensemble methods has provided unique insights into the dynamic nature of this filament and its cellular function. The assembly and disassembly of Rad51 nucleoprotein filaments is seen to be regulated by recombination accessory proteins. In this regard, the BRC repeats of the BRCA2 protein were shown to modulate the DNA binding selectivity of Rad51. Furthermore, single molecule studies explained the need for a DNA translocase, Rad54 protein, in the disassembly of Rad51 double-stranded DNA filaments. PMID- 20299224 TI - Secretive ciliates and putative asexuality in microbial eukaryotes. AB - Facultative sexuality is assumed to have occurred in the ancestor of all extant eukaryotes, but the distribution and maintenance of sex among microbial eukaryotes is still under debate. In this paper, we address the purported asexuality in colpodean ciliates as an exemplary lineage. Colpodeans are a primarily terrestrial clade thought to have arisen up to 900 MYA and contain one known derived sexual species. We conclude that the putative asexuality of this lineage is an observational artifact. We suggest that the same might hold for other microbial eukaryotes, and that many are secretively sexual as well. Theoretical work from the distantly related plants and animals suggests that both the evolutionary success of ancient asexuals and the reversal of the loss of sex are highly unlikely, further suggesting that colpodeans are secretively sexual. However, it remains to be seen to what extent sexual theories and predictions derived from macro-organismic lineages apply also to microbial eukaryotes. PMID- 20299226 TI - Synthesis and biological evaluation of antitumor-active gamma-butyrolactone substituted betulin derivatives. AB - The plant triterpenes betulin and betulinic acid (BA) are triterpenes featuring interesting pharmacological properties. Starting from substituted betulinic aldehydes, we used them as lead structures for the synthesis of several gamma butyrolactones and butenolides. Their antitumor activity was examined for 15 cancer cell lines using a SRB-assay and their apoptotic action was documented by trypan-blue test and DNA laddering. Several compounds revealed a higher activity than betulinic acid. PMID- 20299225 TI - The human Mediator complex: a versatile, genome-wide regulator of transcription. AB - The Mediator complex interacts extensively with the RNA polymerase II enzyme and regulates its ability to express protein-coding genes. The mechanisms by which Mediator regulates gene expression remain poorly understood, in part because the structure of Mediator and even its composition can change, depending upon the promoter context. Combined with the sheer size of the human Mediator complex (26 subunits, 1.2 MDa), this structural adaptability bestows seemingly unlimited regulatory potential within the complex. Recent efforts to understand Mediator structure and function have identified expanded roles that include control of both pre- and post-initiation events; it is also evident that Mediator performs both general and gene-specific roles to regulate gene expression. PMID- 20299227 TI - Synthesis and preliminary pharmacological characterisation of a new class of nitrogen-containing bisphosphonates (N-BPs). AB - A new series of bisphosphonates bearing either the nitrogen-containing NO-donor furoxan (1,2,5-oxadiazole 2-oxide) system or the related furazan (1,2,5 oxadiazole) in lateral chain has been developed. pK(a) values and affinity for hydroxyapatite were determined for all the compounds. The products were able to inhibit osteoclastogenesis on RAW 246.7 cells at 10microM concentration. The most active compounds were further assayed on human PBMC cells and on rat microsomes. Unlike most nitrogen-containing bisphosphonates which target farnesyl pyrophosphate synthase, experimental and theoretical investigations suggest that the activity of our derivatives may be related to different mechanisms. The furoxan derivatives were also tested for their ability to relax rat aorta strips in view of their potential NO-dependent vasodilator properties. PMID- 20299229 TI - Isolation, structure and biological activities of platencin A(2)-A(4) from Streptomyces platensis. AB - Natural products serve as a great reservoir for chemical diversity and are the greatest source for antibacterial agents. Recent discoveries of platensimycin and platencin as inhibitors of bacterial fatty acid biosynthesis enzymes supplied new chemical scaffolds for potential antibacterial agents to overcome resistant pathogens. Discovery of natural congeners augment chemical modification in understanding of structure-activity relationship (SAR). Chemical and biological screening of the extracts led to isolation of three hydroxylated analogs of platencin. The C-12, C-14 and C-15 hydroxylated analogs showed attenuated activities which provided significant understanding of functional tolerance in the diterpenoid portion of the molecule. A truncated and oxidized C-13 natural congener was isolated which suggested direct intermediacy of ent-copalyl diphosphate for the biosynthesis of platensimycins and platencins. PMID- 20299228 TI - Phosphoramidates of 2'-beta-D-arabinouridine (AraU) as phosphate prodrugs; design, synthesis, in vitro activity and metabolism. AB - 2'-Beta-D-arabinouridine (AraU), the uridine analogue of the anticancer agent AraC, was synthesized and evaluated for antiviral activity and cytotoxicity. In addition, a series of AraU monophosphate prodrugs in the form of triester phosphoramidates (ProTides) were also synthesized and tested against a range of viruses, leukaemia and solid tumour cell lines. Unfortunately, neither the parent compound (AraU) nor any of its ProTides showed antiviral activity, nor potent inhibitory activity against any of the cancer cell lines. Therefore, the metabolism of AraU phosphoramidates to release AraU monophosphate was investigated. The results showed carboxypeptidase Y, hog liver esterase and crude CEM tumor cell extracts to hydrolyse the ester motif of phosphoramidates with subsequent loss of the aryl group, while molecular modelling studies suggested that the AraU l-alanine aminoacyl phosphate derivative might not be a good substrate for the phosphoramidase enzyme Hint-1. These findings are in agreement with the observed disappearance of intact prodrug and concomitant appearance of the corresponding phosphoramidate intermediate derivative in CEM cell extracts without measurable formation of araU monophosphate. These findings may explain the poor antiviral/cytostatic potential of the prodrugs. PMID- 20299230 TI - The surface potential of insulating thin films negatively charged by a low-energy focused electron beam. AB - We report on the surface potential characteristics in the equilibrium state of the grounded insulating thin films of several 100 nm thickness negatively charged by a low-energy (<5 keV) focused electron beam, which have been simulated with a newly developed two-dimensional self-consistent model incorporating electron scattering, charge transport and charge trapping. The obtained space charge is positive and negative within and outside the region, respectively, where the electron and hole densities are greater than the trap density. Thus, the surface potential is relatively high around the center, then it decreases to a maximum negative value and finally tends to zero along the radial direction. The position of the maximum value is far beyond the range of e-beam irradiation as a consequence of electron scattering and charge transport. Moreover, a positive electric field can be generated near the surface in both radial and axial directions. The surface potential at center exhibits a maximum negative value in the condition of the approximately 2 keV energy non-penetrating e-beam in this work, which is supported by some existing experimental data in scanning electron microscopy. Furthermore, the surface potential decreases with the increase in beam current, trap density and film thickness, but with the decrease in electron mobility. PMID- 20299231 TI - Quantitative analysis of a complex metal carbide formed during furnace cooling of cast duplex stainless steel using EELS and EDS in the TEM. AB - In this work, a method to determine the atomic ratio of Mo and C within complex metal carbides using EELS in the TEM has been developed. The method is based on the determination of k-factors for given experimental conditions from the EEL spectra of Mo(2)C and MoO(3) standards, which had been independently checked by XRD and EPMA. Factors affecting the k(Mo/C) value of the Mo(2)C standard were also investigated and the value was shown to be insensitive to background subtraction window width but sensitive to prolonged irradiation and specimen thicknesses above a critical value. The method and k-factor obtained from the Mo(2)C standard was applied to spectra from a complex metal carbide precipitate formed during furnace cooling of a cast duplex stainless steel. Using EELS and EDS in the TEM, the composition was estimated to be (Cr(1.52)Fe(2.33)Mo(1.25)Ni(0.17)Si(0.46))C, which is close to M(6)C stoichiometry, and the structure was confirmed by electron diffraction. PMID- 20299232 TI - Antioxidants and redox regulation: changing notions in a changing world. AB - The concepts of antioxidants and redox regulation are reconsidered in the light of recent findings, and some new future challenges for redox biology are outlined. It is suggested that antioxidants, thioredoxin-mediated redox regulation, and signal transduction mediated by reactive oxygen and nitrogen species, are all part of the same broad mechanism. The integration of different redox inputs, by affecting reversible thiol-disulfide dynamics in a set of target proteins, could result in the regulation of key processes such as proteolysis, gene expression and the functioning of selected metabolic pathways. Most interestingly, redox regulation is not just based on a binary "yes or no" response, and is therefore a convenient way to achieve graded control over the continuum of environmental variables. PMID- 20299233 TI - Immunoreactivity of integrin-linked kinase in primary non-small-cell lung cancer and survival after curative resection. AB - OBJECTIVE: Increased immunoreactivity of integrin-linked kinase (ILK) in the primary tumour is an adverse prognostic factor in a variety of preclinical and clinical models of human cancer. Here, we investigate the relationship between ILK immunoreactivity in primary non-small-cell lung cancer (NSCLC) and the survival after curative lung resection. METHODS: Tumour specimens of 138 radically operated NSCLC patients have been retrieved from the pathology archive, mounted in tissue microarrays and immunostained against ILK. The immunoreactivity against ILK has been graded in a semi-quantitative manner (negative or 1-3 positive) by two observers blinded to any patient data, and correlated to the survival data. RESULTS: In total, 88 of 138 tumours (64%) showed an ILK immunoreactivity, which varied significantly between various histological subtypes as it ranged from 46% (squamous cell carcinoma (SCC)) to 79% (adenocarcinoma) (p=0.019). The 5-year cancer-related survival of ILK-positive SCC patients was at 42 + or - 10% versus 72 + or - 9% significantly shorter than in ILK-negative patients (p=0.011). In addition, the recurrence-free survival (RFS) of ILK-positive SCC patients was also significantly shorter than of ILK negative patients (38 + or - 10% vs 60 + or - 10%) (p=0.005). In multivariate analysis, ILK expression was a significant prognostic factor for RFS in squamous cell carcinoma (p=0.018), but not in adenocarcinoma or in the rare histology group. CONCLUSIONS: Primary NSCLC tumours show a variable ILK immunoreactivity, dependent on the histological subtype. In SCC, ILK immunoreactivity is a significantly adverse prognostic factor. PMID- 20299235 TI - Left atrial appendage contributes to left atrial booster function after the maze procedure: quantitative assessment with multidetector computed tomography. AB - OBJECTIVE: Although the left atrial appendage (LAA) is excised to prevent thrombosis in the maze procedure, it remains unclear whether LAA is retained in expectation of LAA booster function. Therefore, we quantitatively assessed LAA size and function after the maze procedure in patients with chronic atrial fibrillation (AF) and mitral valve disease (MVD), and compared with those in patients with sinus rhythm after coronary artery bypass grafting (CABG). METHODS: We studied 23 patients (maze group: 65.0 + or - 9.2 (SD) years) undergoing the maze procedure for chronic AF and mitral valve surgery and 16 patients having sinus rhythm after CABG (CABG group: 66.5 + or - 9.3 years). The maze procedure was conducted by radiofrequency (RF) ablation and LAA was preserved in all cases. Left atrium (LA) and LAA volume and booster function were quantitatively evaluated by multidetector computed tomography (MDCT) at 11.7 + or - 10.4 months (maze group) and 16.8 + or - 19.9 months (CABG group) after the surgery. RESULTS: In all 23 patients of the maze group, sinus rhythm was well restored. LAA was clearly visualised without thrombi in all 39 patients. The maximal LA volume in the maze group was 128.8 + or - 54.6 ml, being larger than 105.3 + or - 36.1 ml in the CABG group. LA ejection fraction (EF) in the maze group was 16.1 + or - 7.0%, being significantly lower than 26.8 + or - 8.7% in the CABG group. Meanwhile, the maximal LAA volume in the maze group was significantly larger (16.9 + or - 7.3 ml vs 8.4 + or - 4.7 ml), but LAA EF (34.1 + or - 12.8% vs 36.1 + or - 7.4%) was comparable in the two groups. CONCLUSION: LAA largely contributes to LA booster function, particularly in the maze group, because LA booster function is deteriorated in this group of patients. PMID- 20299236 TI - Nutritional processes of care for older adults admitted to an oncology-acute care for elders unit. AB - BACKGROUND: Acute care for elders (ACE) units have been established in the United States to prevent functional decline in older hospitalized patients. PURPOSE: We sought to examine whether an ace unit that focused specifically on care of older oncology patients (OACE) compared with a usual care cancer ward (UCCW) demonstrated improved nutritional processes of care in patients who had documentation of nutritional deficits. METHODS: We conducted a retrospective chart review to examine whether orders had been placed for a nutritional consult or use of nutritional supplements. Logistic regression analyses, controlling for confounding variables, were conducted to evaluate differences between the wards. RESULTS: OACE unit patients were 2.1 times more likely than UCCW patients to have a nutrition consult placed and 2.5 times more likely to have nutritional supplements ordered. CONCLUSIONS: An OACE unit model of care resulted in increased nutritional interventions. Future work is warranted to evaluate outcomes of care. PMID- 20299237 TI - Interferon-alpha, -beta and -gamma induce CXCL9 and CXCL10 secretion by human thyrocytes: modulation by peroxisome proliferator-activated receptor-gamma agonists. AB - It has been hypothesized that interferon (IFN) alpha and beta cause autoimmune thyroid dysfunctions by changing the Th1/Th2 balance, but the mechanisms involved are not yet known. The aims of this study were: (a) to test the effect of IFNalpha, IFNbeta and IFNgamma on the secretion of the Th1 chemokines CXCL9 and CXCL10, in "primary cultures of human thyroid follicular cells" (TFC); (b) to assess the effect of PPARgamma activation on CXCL9 and CXCL10 secretion. In TFC, CXCL9 and CXCL10 were undetectable in the supernatant. IFNgamma, IFNalpha and IFNbeta, dose dependently induced CXCL9 and CXCL10 release. TNFalpha alone had no effect. The combination of each of the IFNs with TNFalpha had a significant synergistic effect on CXCL9 and CXCL10 secretion. Treatment of TFC with rosiglitazone dose dependently inhibited the IFNs-stimulated CXCL9 and CXCL10 release. Compared with IFNalpha and IFNbeta, IFNgamma was the most potent stimulus of CXCL9 and CXCL10 secretion. In conclusion, IFNalpha, IFNbeta, IFNgamma and TNFalpha (synergistically with IFNs) dose-dependently induce the release of CXCL9 and CXCL10 by TFC, suggesting that this process may be related, at least in part, to the appearance of thyroid dysfunction during IFNs therapy. Furthermore, PPARgamma activation partially inhibits this process. PMID- 20299238 TI - Monocyte chemoattractant protein-1: a dichotomous role in cardiac remodeling following acute myocardial infarction in man? AB - INTRODUCTION: Monocyte chemoattractant protein-1 (MCP-1) is elevated after acute myocardial infarction (AMI), and potentiates left ventricular (LV) remodeling in murine models of AMI. We examined the relationships between serum MCP-1, change in LV function and biomarkers related to remodeling in a cohort of AMI patients. METHODS: Serum MCP-1 concentrations were measured in 100 patients (age 58.9+/ 12.0 years, 77% male) admitted with AMI and LV dysfunction, at baseline (mean 46 h), 12 and 24 weeks; cardiac magnetic resonance imaging and measurement of matrix metalloproteinase-2 (MMP-2), MMP-3 and MMP-9 occurred at each time-point. RESULTS: MCP-1 increased significantly from 697 [483, 997]pg/mL at baseline to 878 [678, 1130]pg/mL at 24 weeks (p<0.001). MMP-3 concentration increased while MMP-9 decreased significantly over time; MMP-2 concentration did not change significantly. BASELINE MCP-1 correlated with change in (Delta) LV end-systolic volume index (DeltaLVESVI; r= -0.48, p=0.01) and with DeltaLV ejection fraction (DeltaLVEF; r=0.50, p=0.02). However, DeltaMCP-1 correlated positively with DeltaLVESVI (r=0.40, p=0.006) and negatively with DeltaLVEF (r= -0.36, p=0.004). MCP-1 had no relationship with any MMP. CONCLUSIONS: MCP-1 may have a dichotomous role following AMI, aiding early infarct healing but potentiating later remodeling, which merits further study before any therapeutic trials of MCP-1 modulation in humans. PMID- 20299239 TI - Gas phase structure of micro-hydrated [Mn(ClO4)]+ and [Mn2(ClO4)3]+ ions probed by infrared spectroscopy. AB - Gas-phase infrared photodissociation spectroscopy is reported for the microsolvated [Mn(ClO(4))(H(2)O)(n)](+) and [Mn(2)(ClO(4))(3)(H(2)O)(n)](+) complexes from n = 2 to 5. Electrosprayed ions are isolated in an ion-trap where they are photodissociated. The 2600-3800 cm(-1) spectral region associated with the OH stretching mode is scanned with a relatively low-power infrared table-top laser, which is used in combination with a CO(2) laser to enhance the photofragmentation yield of these strongly bound ions. Hydrogen bonding is evidenced by a relatively broad band red-shifted from the free OH region. Band assignment based on quantum chemical calculations suggest that there is formation of water-perchlorate hydrogen bond within the first coordination shell of high spin Mn(II). Although the observed spectral features are also compatible with the formation of structures with double-acceptor water in the second shell, these structures are found relatively high in energy compared with structures with all water directly bound to manganese. Using the highly intense IR beam of the free electron laser CLIO in the 800-1700 cm(-1), we were also able to characterize the coordination mode (eta(2)) of perchlorate for two clusters. The comparison of experimental and calculated spectra suggests that the perchlorate Cl-O stretches are unexpectedly underestimated at the B3LYP level, while they are correctly described at the MP2 level allowing for spectral assignment. PMID- 20299240 TI - Backbone and side-chain specific dissociations of z ions from non-tryptic peptides. AB - Backbone z-type fragment ions formed by electron-transfer dissociation (ETD) of doubly protonated peptides AAHAL, AHDAL, and AHADL were subjected to collisional activation and their dissociation products were studied by ETD-CID-MS(3) and MS(4). Electron structure theory calculations were performed to elucidate ion structures and reaction mechanisms. All z ions showed competitive eliminations of C(3)H(7) and C(4)H(8) from the C-terminal Leu side chain. The energetics and kinetics of these dissociations were studied computationally for the z(4) ion from AAHAL, and optimized structures are reported for several intermediates and transition states. RRKM calculations on the combined B3LYP and PMP2/6 311++G(2d,p) potential energy surface provided unimolecular rate constants that closely reproduced the experimental branching ratios for C(3)H(7) and C(4)H(8) eliminations. Mechanisms were also studied for the loss of CO(2) from z ions generated by ETD of AHDAL and AHADL and for a specific radical-induced Asp C(alpha)-CO backbone cleavage. CID of the z ions under study did not produce any fragment ions that would indicate cascade backbone dissociations triggered by the radical sites. In contrast, the majority of backbone dissociations occurred at bonds that were remote from the radical sites (spin-remote dissociations) and were triggered by proton migrations that were analogous to those considered for standard peptide ion fragmentations. PMID- 20299241 TI - Application of femtosecond laser mass spectrometry to the analysis of volatile organic compounds. AB - Femtosecond (fs) lasers have high intensity and ultrashort pulse duration. Tunneling ionization occurs for molecules subject to such intense laser fields. We have studied the mass spectra of a variety of molecules irradiated by intense fs laser pulses. These molecules include some typical volatile organic compounds contained in human breath and in the atmosphere. The results demonstrate that all of these molecules can be ionized by intense fs laser pulses. Dominant parent ion and some characteristic ionic fragments are observed for each molecule. The degree of fragmentation can be controlled by adjusting the laser intensity. Moreover, saturation ionization can occur for each molecule by increasing the laser intensity. These features indicate that fs laser mass spectrometry can be a sensitive tool to identify and quantify volatile organic compounds in human breath. PMID- 20299242 TI - Listeria and Salmonella bacterial vectors of tumor-associated antigens for cancer immunotherapy. AB - This review covers the use of the facultative intracellular bacteria, Listeriamonocytogenes and Salmonella enterica serovar typhimurium as delivery systems for tumor-associated antigens in tumor immunotherapy. Because of their ability to infect and survive in antigen presenting cells, these bacteria have been harnessed to deliver tumor antigens to the immune system both as bacterially expressed proteins and encoded on eukaryotic plasmids. They do this in the context of strong innate immunity, which provides the required stimulus to the immune response to break tolerance against those tumor-associated antigens that bear homology to self. Here we describe differences in the properties of these bacteria as vaccine vectors, a summary of the major therapies they have been applied to and their advancement towards the clinic. PMID- 20299243 TI - Chicken scFvs and bivalent scFv-C(H) fusions directed against HSP65 of Mycobacterium bovis. AB - Two chicken single-chain variable region antibody fragments (scFvs) that recognised the 65 kDa heat-shock protein (HSP65) of Mycobacterium bovis were selected from a large semi-synthetic phage displayed library. Both recognised HSP65 in indirect enzyme-linked immunosorbent assay (ELISA) and immunoblots and retained their activity during storage. Neither, however, could function as the capture reagent in a sandwich ELISA when immobilised on polystyrene. To establish whether they could be engineered for general use in immunotests, the genes coding for these scFvs were subcloned in expression vectors that contained sequences encoding chicken IgY heavy-chain constant region domains. This resulted in larger bivalent constructs which more closely resembled IgY molecules. The engineered fragments were evaluated in ELISAs and gold-conjugated immunochromatographic tests (ICTs). In contrast to their previous behaviour as scFvs, the modified fragments (designated "gallibodies") could be used for immunocapture in ELISA and could be readily conjugated to colloidal gold nanoparticles. A sandwich ICT that could detect recombinant HSP65 was also devised. Although converting the recombinant single-chain monomeric antibody fragments to bivalent immunoglobulin like molecules did not entirely 'standardise' the behaviour of the scFvs, this approach remains potentially useful for developing practical, robust, immunodiagnostic reagents. PMID- 20299244 TI - Guidelines for establishing a quality improvement program in interventional radiology. PMID- 20299245 TI - Endovascular management of critical limb ischemia. AB - Endovascular management of critical limb ischemia has advanced significantly in the recent past, especially the ability to treat tibial artery lesions with reasonable results. The indications, results, and technical aspects or endovascular management of CLI is reviewed herein. An algorithm for clinical management of CLI in patients with tibial occlusive disease is also presented. PMID- 20299246 TI - Treatment outcomes of mandibular advancement devices in positional and nonpositional OSA patients. AB - OBJECTIVE: The aim of the study was to investigate treatment outcome of mandibular advancement devices (MADs) for positional and nonpositional obstructive sleep apnea (OSA). STUDY DESIGN: Forty-two positional (supine apnea hypopnea index [AHI] > or = 2 times lateral AHI) and 30 nonpositional (supine AHI < 2 times lateral AHI) OSA patients performed 2-nights of sleep study before and after insertion of MADs. RESULTS: The decreases in apnea severity based on a reduction in the overall and supine AHI values after MADs therapy were significantly greater for the positional OSA than nonpositional OSA group. A multiple linear regression analysis showed that decrease in overall AHI was significantly associated with being in the positional group (standardized coefficient = 0.505). Age, body mass index, gender, and time in supine position during sleep did not show significant associations with decrease in overall AHI after MAD therapy. CONCLUSION: Our data suggest that MADs are more effective in positional OSA than nonpositional OSA patients. PMID- 20299247 TI - Cleft maxillary distraction versus orthognathic surgery--which one is more stable in 5 years? AB - OBJECTIVE: The objective of this study was to compare the long-term stability of distraction osteogenesis (DO) and conventional orthognathic surgery (CO) in patients with cleft lip and palate (CLP). STUDY DESIGN: CLP patients requiring maxillary advancement of 4 to 10 mm were randomized and assigned to either CO or DO. In the CO group, the maxilla was fully mobilized to the preplanned position and fixed using titanium miniplates. In the DO group, the maxilla was mobilized to a limited extent and distractors were fixed on each side of the maxilla. Serial lateral cephalographs were taken for the assessment of stability at different postoperative periods up to 5 years. RESULTS: In the CO group, the maxilla relapsed backward and upward, whereas in the DO group, it advanced more forward and downward over 5 years. CONCLUSIONS: Distraction of the cleft maxilla can achieve better long-term skeletal stability in maintaining its advanced position than CO. PMID- 20299248 TI - Complication rates of operatively treated mandibular fractures--the mandibular neck. AB - BACKGROUND: Surgical treatment of mandibular neck fractures is frequently associated with postoperative complications. This study aims at an in-depth analysis of complication rates of surgically treated mandibular neck fractures. METHODS: All treated patients (264 male, 103 female patients, with 429 mandibular neck fractures) of the Vienna University Clinic of Maxillofacial Surgery in the period of 1995 to 2005 with at least 1 mandibular neck fracture were included. RESULTS: Of surgically treated fractures, 94.8% healed successfully after 1 open reduction, 4.4% had 2, and 0.8% had 3 open reductions. Osteosynthesis failure was 11.3% for 1 miniplate, 6.7% for 2 miniplates, and 8.5% for 1 lag screw. Of the surgically treated, 53 (21.3%) had 1 complication, 12 (4.8%) had 2, and 4 (1.6%) had 3 complications. Comparing isolated and mandibular neck fractures combined with other mandibular fractures the risk of suffering osteosynthesis failure is 3.59 in case of isolated (P = .004). CONCLUSIONS: Predominant causes of revision surgery are osteosynthesis failure, pseudarthrosis, and malposition. PMID- 20299249 TI - Shoulder mobility after spinal accessory nerve-sparing modified radical neck dissection in oral cancer patients. AB - OBJECTIVE: Radical neck dissection (RND), a standard surgical procedure for lymph node metastasis of head and neck cancer for decades, causes various dysfunctions, such as pain or limited abduction of the shoulder. Various RND modifications have been made to reduce these postoperative dysfunctions, but the effect of preservation of the spinal accessory nerve is still controversial. The aim of this study was to explain our surgical method of sparing the accessory nerve during neck dissection and to clarify the effect of preserving the nerve on reduction in shoulder dysfunction. STUDY DESIGN: One hundred five neck dissections were performed in 90 patients with oral cancer: 4 RNDs and 101 modified radical neck dissections (mRNDs). The spinal accessory nerve was preserved in 96 neck dissections. Dysfunction of the trapezius muscle was evaluated by the limitation of shoulder lateral abduction at 3 months after the operation. RESULTS: All 9 patients with resection of the spinal accessory nerve showed severe shoulder dysfunction, whereas 90 out of 96 with preservation of the nerve maintained normal shoulder function. CONCLUSION: Spinal accessory nerve sparing neck dissection can reduce postoperative shoulder dysfunction if careful operating procedures are used. PMID- 20299250 TI - Cervical lymph nodes with or without metastases from oral squamous carcinoma: a correlation of MRI findings and histopathologic architecture. AB - OBJECTIVES: The aim of this study was to describe the magnetic resonance images (MRIs) of the architecture of metastatic lymph nodes as well as healthy lymph nodes and to correlate the images with the histopathologic architecture of the lymph nodes from oral squamous cell carcinoma. STUDY DESIGN: The signal intensities of 98 cervical lymph nodes from 20 patients with oral squamous cell carcinoma were evaluated on T2-weighted and diffusion-weighted whole-body imaging with background body signal suppression (DWIBS). The MRI findings were compared with the histopathologic architecture. RESULTS: On T2-weighted images, very hyperintense and/or isointense areas were specific findings for lymph nodes containing metastases from oral squamous cell carcinoma. Histopathology indicated that these areas corresponded to cystic degeneration or keratinization. Using DWIBS images with inverted black-and-white image contrast, cystic degeneration, keratinization, fibrous tissue, tumor tissue, and lymphoid tissue were either hypointense or intermediate in intensity. CONCLUSIONS: On T2-weighted images, very hyperintense and/or isointense areas were characteristic findings for lymph nodes containing metastases from oral squamous cell carcinoma. This suggests cystic degeneration or keratinization within the affected lymph nodes. Using DWIBS images, it was difficult to differentiate metastatic from benign lymph nodes. PMID- 20299251 TI - Risk factors affect the survival outcome of hard palatal and maxillary alveolus squamous cell carcinoma: 10-year review in a tertiary referral center. AB - OBJECTIVE: Hard palatal cancer is relatively rare in the head and neck region. Treatment outcome, risk factors that lead to poor survival outcome, and treatment strategy are still controversial. STUDY DESIGN: Retrospective study in a tertiary medical center. RESULTS: Surgery is a better treatment strategy than concurrent chemoradiation therapy (CCRT) for achieving positive survival outcomes. We also found a higher surgical salvage rate in patients with hard palatal cancer who had local recurrence or neck relapse. Soft palate or infratemporal fossa involvement had poor outcomes. Ulcerative tumor features, tumor volumes larger than 10 mL, and local recurrent tumors that could not undergo salvage surgery also had poorer survival outcomes in our study. CONCLUSION: Surgical management is still the first choice for patients with hard palate or alveolus squamous cell carcinomas even when patients had local or neck regional recurrence. PMID- 20299253 TI - Self inhibition of phagocytosis: the affinity of 'marker of self' CD47 for SIRPalpha dictates potency of inhibition but only at low expression levels. AB - Phagocytes engulf foreign cells but not 'self' in part because self cells express CD47 as a ligand for signal regulatory protein SIRPalpha, which inhibits phagocytosis. Motivated by reports of upregulation of CD47 on both normal and cancerous stem cells [1: Jaiswal et al., 2009] and also by polymorphisms in SIRPalpha [2: Takenaka et al., 2007], we show here that inhibition of engulfment correlates with affinity of CD47 for SIRPalpha - but only at low levels of CD47. One common human polymorph of SIRPalpha is studied and binds more strongly to human-CD47 than to mouse-CD47 (K(d) approximately 0.12 microM and 6.9 microM, respectively) and does not bind sheep red blood cells (RBCs) - which are well established targets of human macrophages; in comparison, a common mouse polymorph of SIRPalpha binds with similar affinity to human and mouse CD47 (K(d) approximately 0.22 microM). Using immunoglobulin (IgG)-opsonized particles with varying levels of either human- or mouse-CD47, the effective inhibition constants K(i) for blocking phagocytosis are then determined with both human- and mouse derived macrophages. Only human phagocytes show significant differences in man versus mouse K(i)'s and only at CD47 levels below normal densities for RBCs. While phospho-signaling through human-SIRPalpha shows similar trends, consistent again with the affinity differences, saturating levels of CD47 (>K(i)) can signal and inhibit phagocytosis regardless of man versus mouse. Quantitative analyses here prompt more complete characterizations of both CD47 levels and SIRPalpha polymorphisms when attempting to study in vivo effects of these key proteins in innate immunity. PMID- 20299254 TI - Cord blood screening for alpha-thalassemia and hemoglobin variants by isoelectric focusing in northern Thai neonates: correlation with genotypes and hematologic parameters. AB - We describe the screening of newborns for thalassemia and Hb variants by using isoelectric focusing (IEF) in a population from northern Thailand where hemoglobinopathies are highly prevalent. The report focuses on findings of alpha thalassemia, Hb E, and other hemoglobin variants, and their correlation with genotypes and hematologic parameters. Two-hundred and seven out of 566 newborns (36.6%) had thalassemia genes or Hb variants. Seventeen different genotypes were found. Nine cases (1.6%) of Hb H disease (five deletional Hb H diseases, two Hb H/Constant Spring diseases, one deletional Hb H disease/Hb E, carrier and one Hb H/Constant Spring disease/Hb E carrier) and one Hb E-beta-thalassemia were identified. IEF could clearly distinguish Hb H diseases and carriers of two alpha globin gene defects from normal individuals according to the presence of Hb Bart's and its percentage. For carriers of a single alpha-globin gene defect, Hb Bart's was either absent or present in a small amount and was therefore not reliable for screening. The presence of an additional band at the Hb A(2) position in the newborns signified an Hb E carrier. One case of an absent Hb A and a presence of Hb E was identified as Hb E-beta-thalassemia. Two Hb Q-Thailand carriers were seen with two additional Hb fractions, presumably combinations of gamma-globin and beta-globin with the alpha-globin variant. Newborns with Hb H disease had lower Hb, MCV, and MCH levels than normal. MCV and MCH were also useful for differentiation of carriers of two alpha-globin gene defects, but not for carriers of Hb E or single alpha-globin gene defect. IEF was a reliable method for neonatal cord blood screening for alpha-thalassemia and Hb variants. PMID- 20299256 TI - Eradication of Mycoplasma hyopneumoniae from a swine finishing herd without total depopulation. AB - Using vaccination and medication, Mycoplasma hyopneumoniae (Mhyo) was eradicated from a finishing herd without total depopulation. Altogether 3243 feeder pigs originating from Mhyo-free herds were vaccinated once using an inactivated, adjuvanted vaccine before transporting them to a Mhyo-infected finishing herd. The Mhyo-infected groups of pigs were medicated with antimicrobial agents at the time of the arrival of the first groups of Mhyo-free, vaccinated feeder pigs. The groups were operated with an all-in-all-out method in rooms with separate ventilation and slurry disposal systems. Thereafter the farmer purchased only non vaccinated feeder pigs originating from Mhyo-free sow herds. Serology gave no positive results for 5.5 years and it was concluded that the eradication programme had been successful in producing a Mhyo-free herd without total depopulation. PMID- 20299257 TI - A non-uniformly sampled 4D HCC(CO)NH-TOCSY experiment processed using maximum entropy for rapid protein sidechain assignment. AB - One of the stiffest challenges in structural studies of proteins using NMR is the assignment of sidechain resonances. Typically, a panel of lengthy 3D experiments are acquired in order to establish connectivities and resolve ambiguities due to overlap. We demonstrate that these experiments can be replaced by a single 4D experiment that is time-efficient, yields excellent resolution, and captures unique carbon-proton connectivity information. The approach is made practical by the use of non-uniform sampling in the three indirect time dimensions and maximum entropy reconstruction of the corresponding 3D frequency spectrum. This 4D method will facilitate automated resonance assignment procedures and it should be particularly beneficial for increasing throughput in NMR-based structural genomics initiatives. PMID- 20299255 TI - Approaches to unravel the genetics of sleep. AB - Sleep and circadian rhythms are complex and inter-connected physiological processes. Relative to the remarkable progress made in identifying the genetic basis of circadian rhythms and some specific sleep disorders, efforts to identify genetic variants associated with normal variation in sleep have progressed more slowly. Two key issues concerning the design of such studies must be addressed in order to facilitate further progress. The first concerns the sleep related traits to be targeted. The second issue is the choice of the gene-mapping method (linkage, candidate gene association or genome-wide association). This paper discusses these issues, reviews published studies of sleep phenotypes, and recommends cost-effective methods to advance knowledge of the genetic determinants of normal sleep patterns. PMID- 20299258 TI - New insights in nutritional management and amino acid supplementation in urea cycle disorders. AB - Sodium phenylbutyrate is used in the pharmacological treatment of urea cycle disorders to create alternative pathways for nitrogen excretion. The primary metabolite, phenylacetate, conjugates glutamine in the liver and kidney to form phenylacetylglutamine that is readily excreted in the urine. Patients with urea cycle disorders taking sodium phenylbutyrate have a selective reduction in the plasma concentrations of branched chain amino acids despite adequate dietary protein intake. Moreover, this depletion is usually the harbinger of a metabolic crisis. Plasma branched chain amino acids and other essential amino acids were measured in control subjects, untreated ornithine transcarbamylase deficiency females, and treated patients with urea cycle disorders (ornithine transcarbamylase deficiency and argininosuccinate synthetase deficiency) in the absorptive state during the course of stable isotope studies. Branched chain amino acid levels were significantly lower in treated patients with urea cycle disorders when compared to untreated ornithine transcarbamylase deficiency females or control subjects. These results were replicated in control subjects who had low steady-state branched chain amino acid levels when treated with sodium phenylbutyrate. These studies suggested that alternative pathway therapy with sodium phenylbutyrate causes a substantial impact on the metabolism of branched chain amino acids in patients with urea cycle disorders, implying that better titration of protein restriction can be achieved with branched chain amino acid supplementation in these patients who are on alternative pathway therapy. PMID- 20299259 TI - Mouse model of encephalopathy and novel treatment strategies with substrate competition in glutaric aciduria type I. AB - Glutaric aciduria type I (GA-1) results from an inherited defect in a common step of lysine, hydroxylysine and tryptophan metabolism. This defect is associated with an age-dependent susceptibility to encephalopathy commonly preceded by non specific childhood illnesses or fasting. The brain injury that develops with encephalopathic crisis in GA-1 is anatomically and symptomatically similar to Huntington's disease, affecting the striatum. The mechanism of injury remains poorly understood. Recently, an animal model of GA-1 encephalopathy was developed by providing GA-1 mice with added dietary lysine. This model shows age-dependent susceptibility similar to the human disease. Enhanced lysine accumulation and utilization in the immature brain correlates with increased glutaric acid levels and age-dependent susceptibility. Neurotransmitter and Krebs cycle intermediate depletion in this model represent novel findings toward uncovering the mechanism of neuronal injury. Additionally this mouse model is responsive to glucose analogous to human GA-1 and provides insight toward the mechanism of this effect. Together these findings led to a new treatment strategy of competing with brain lysine uptake that shows promising results. This research serves as a model for understanding blood brain barrier amino acid transport at critical stages of development and may help advance understanding of brain injury and development of treatments in other IEMs including urea cycle disorders. PMID- 20299260 TI - Response to Choi et al. regarding the use of a Gaucher diagnostic kit. PMID- 20299261 TI - [Capitate osteotomy in Kienbock's disease in twelve cases. Clinical and radiological results at five years follow-up]. AB - Kienbock's disease could occur pain and reduce wrist's range of motion despite of an early radiologic staging. Usual surgical procedures unload the lunate. Radial shortening is the common procedure in negative ulnar variance. For wrists with neutral or positive ulnar variance, this procedure could produce a distal radio ulnar discrepancy and an ulnocarpal impingement. We perform, in these cases, a capitate shortening. The goal of this study is to relate the wrist functional outcome and the radiological result in 12 cases. It was a consecutive retrospective study of 12 patients (nine male, three female). Eight Lichtman's stage II and four stage III A with neutral or positive ulnar variance. The wrists were painful and with a reduce range of motion. The surgical procedure consisted in a dorsal approach and a 2-mm shortening osteotomy in the capitate's waist. Bone clips were used for fixation. The follow-up average period was 65.8 months. All patients had pain relief. The wrist's range of motion improved in all cases. Any single complication was noted. The patients recovered their professional or usual occupation with an average of 3.6 months. Lunate's vascularization improved in all cases. Any intracarpal complication or capitate non-union occured. The capitate shortening is a simple and low aggressive procedure. Wrist's functional outcome has good results. We recommend this procedure for symptomatic patients in early Kienbock's disease with neutral or positive ulnar variance. PMID- 20299262 TI - [Multicentric study of thrombosis prevention in upper-extremity microsurgery. Survey at the Fesum centers]. AB - Thrombosis is still the first cause of microsurgery failure. Lots of publications have been made but no consensus exists. We first analysed the results of our study in 53 French expert surgeons, then we compared them with the last published datas, most of all, with the similar surveys. If a big majority (81 %) of the surgeons use a preventing method, we observed majors variations between them and also compared to the anglosaxons surgeons habits. This survey permits to make the point on today's practice and to show that some of them are based on low proof level and something even done without any medical references. After datas analysis, we observed that none of the medical treatments proved efficiency on preventing vascular thrombosis. The low molecular weight heparins (LMWH) could be used on postops without increase bleeding but not to lower specially the microvascular thrombosis rate. Aspirin did not improve the positive rates and its adjonction to LMWH increased the bleeding. Until scientific studies prove efficacy of a treatment, the surgeon has to make a personal choice: keeping habits or following evidence-based medicine. PMID- 20299263 TI - Arthroscopic treatment of a fresh lunate bone fracture detaching the scapholunate ligament. AB - Fractures of the lunate bone are rare and usually treated by prolonged immobilization. We report a fracture of the dorsal pole of the lunate bone detaching the scapholunate ligament. The clinical presentation was equivalent to an acute disruption of this ligament. Percutaneous screw repair of the bone fragment was performed under wrist arthroscopy. The patient kept an analgesic splint for five days and early mobilization was provided. After 6 weeks, the patient had returned to his previous level of activity with normal wrist motion and full strength. Screw fixation under arthroscopy is minimally invasive and provides accurate restoration of the lunar anatomy, yielding good functional results after a short recovery period. This treatment offers a satisfactory alternative to prolonged immobilization and ensures good reduction and compression of the fracture. We present a detailed description of the surgical technique and its results. PMID- 20299264 TI - Melorheostosis of the humerus: a rare differential diagnosis of carpal tunnel syndrome. AB - Melorheostosis is an uncommon and rare linear hyperostosis, which can be complicated by soft tissue changes. We present a case of this disorder in the humerus, clinically referred because of carpal tunnel syndrome. Although treatment is usually conservative, in this case, a neurolysis and resection of the sclerotic bone were done with good clinical result. PMID- 20299265 TI - Continuous at-home postoperative analgesia using a catheter in the case of hand surgery: preliminary study about 40 cases. AB - In hand surgery, ever since continuous at-home postoperative analgesia (CPA) was implemented, procedures which cause pain for more than 24h can now be performed in ambulatory surgery. The aim of our work was to study the feasibility of CPA. Our series comprised 40 patients with a mean age of 50 years. Twenty-four patients had an ASA score of 1 and 16 patients had an ASA score of 2. Indications were osteoarthritis and rheumatoid diseases. Three steps were involved: preoperative (patient screening and information), peroperative (placement of a peripheral nerve catheter through an axillary approach using an elastomeric device) and postoperative (at-home patient care provided by visiting nurses). Evaluation was rated using a CPA score (0 to 10) based on analgesia quality and network organization data. The global CPA score was 1.85. The quality of analgesia (2.6) scored less than the quality of organization (1.1). In the case of analgesia, sleep obtained the lowest score, followed by pain, and lastly, unwanted events. As far as organization was concerned, the network obtained the lowest score, followed by patient satisfaction, and lastly, patient information. Problems were encountered due to insufficient nurse training, analgesia failures, as well as unwanted events related to the oral antalgic treatment. However, technical success was almost always achieved. Our results show that the indications for ambulatory surgery could be extended and hospital-private practice networks be further developed. CPA appears to be a promising technique for analgesia and ambulatory surgery. PMID- 20299266 TI - [Letter to the author of the article: "Pronator quadratus preservation for distal radius fractures with locking palmar plate osteosynthesis. Surgical technique"]. PMID- 20299267 TI - [Intrauterine ischemia of the right upper limb and hemiface: a case report]. AB - A case of ischemic gangrene of the right upper limb and hemiface noticed at birth is reported. It was a male baby born at term vaginally from a non diabetic mother. He was allowed in the surgical emergencies, 24 hours after the birth. The injuries were irreversible and required an arm amputation and a debridement of necrotic areas of the hemiface. The authors discuss the aetiology, the clinical features and the management of this rare condition. PMID- 20299268 TI - [Treatment of fractures of proximal phalanx of fingers by Eiffel Tower percutaneous pinning method. A review of 45 cases]. AB - The authors report in the treatment of fractures of the proximal phalanx of the fingers, the use of Eiffel Tower pinning, a relatively simple method, fast and stable, associated to a protection and early rehabilitation. The objective of this method is to offer to the patient a pollici-digital grip. Our study is a retrospective study of 45 patients treated for fractures of the proximal phalanx of the fingers by percutaneous pinning according to Eiffel Tower method. We detail this simple and economic technique and examine the functional and radiological results of this series of patients. The amplitude of the active total motion of the proximal interphalangeal joint is on average 94.16 degrees (78.5 % of the normal active mobility of the proximal interphalangeal joint), and the amplitude of the active total motion of the metacarpo-phalangeal joint is on average 90.05 degrees (75 % of the normal active mobility of the metacarpo phalangeal joint). PMID- 20299269 TI - Ultrasound-promoted greener synthesis of benzoheterocycle derivatives catalyzed by nanocrystalline copper(II) oxide. AB - CuO nanoparticles provide an efficient, economic, and novel method for the synthesis of quinoxaline, benzoxazine, and benzothiazine under ultrasonic irradiation. The protocol offers advantages in terms of higher yields, short reaction times, and mild reaction conditions, with reusability of the catalyst. PMID- 20299270 TI - Determination of backrest inclination based on biodynamic response study for prevention of low back pain. AB - Whole-body vibration experiments with subjects under vertical vibration were performed to examine and evaluate effects of backrest inclination on vibration transmitted through seats to the human body by using biodynamic response parameters represented by apparent mass (APMS) and vibration power absorption (VPA). The biodynamic response parameters of twelve male subjects, exposed to vertical random vibration at 0.8 m/s(2) r.m.s., were characterized under three different backrest support conditions, with the upper body supported against backrest inclined at angles of 0 degrees (vertical), 10 degrees, and 30 degrees with respect to the vertical axis. An increased backrest inclination angle resulted in reduction of the total power absorption calculated particularly the frequency range of 1-20 Hz. Normalized APMS magnitudes showed a principal resonance at about 5 Hz for each subject for a backrest supported vertically. A second resonant peak appeared at about 7.5 Hz in addition to the primary resonant peak for a backrest inclined at an angle of 10 degrees and then became much steeper for a backrest inclined at angle of 30 degrees. For a backrest inclined at an angle of 30 degrees, the resonant peak at 5 Hz was less apparent than in other backrest inclination postures. All subjects showed the second resonant peak at about 7.5 Hz in the double-normalized VPA for a backrest inclined at an angle of 30 degrees. According to the evaluation of vibration absorption behavior performed in this study, backrest inclination angle is preferable between 10 degrees and 30 degrees from the viewpoint of prevention of low back pain disorder. PMID- 20299271 TI - Evaluation of the optimal lengths and number of multiple windows for spectrogram estimation of SSVEP. AB - The purpose of this paper is to present the optimal number of windows and window lengths using multiple window spectrogram for estimation of non-stationary processes with shorter or longer duration. Such processes could start in the EEG as a result of a stimuli, e.g., steady-state visual evoked potentials (SSVEP). In many applications, the Welch method is used with standard set-ups for window lengths and number of averaged spectra/spectrograms. This paper optimizes the window lengths and number of windows of the Welch method and other more recent, so called, multiple window or multitaper methods and compares the mean squared errors of these methods. Approximative formulas for the choice of optimal number of windows and window lengths are also given. Examples of spectrogram estimation of SSVEP are shown. PMID- 20299273 TI - A fast and robust patient specific Finite Element mesh registration technique: application to 60 clinical cases. AB - Finite Element mesh generation remains an important issue for patient specific biomechanical modeling. While some techniques make automatic mesh generation possible, in most cases, manual mesh generation is preferred for better control over the sub-domain representation, element type, layout and refinement that it provides. Yet, this option is time consuming and not suited for intraoperative situations where model generation and computation time is critical. To overcome this problem we propose a fast and automatic mesh generation technique based on the elastic registration of a generic mesh to the specific target organ in conjunction with element regularity and quality correction. This Mesh-Match-and Repair (MMRep) approach combines control over the mesh structure along with fast and robust meshing capabilities, even in situations where only partial organ geometry is available. The technique was successfully tested on a database of 5 pre-operatively acquired complete femora CT scans, 5 femoral heads partially digitized at intraoperative stage, and 50 CT volumes of patients' heads. In the latter case, both skin and bone surfaces were taken into account by the mesh registration process in order to model the face muscles and fat layers. The MMRep algorithm succeeded in all 60 cases, yielding for each patient a hex-dominant, Atlas based, Finite Element mesh with submillimetric surface representation accuracy, directly exploitable within a commercial FE software. PMID- 20299274 TI - Exploiting cyanobacterial P450 pathways. AB - Cytochrome P450s are hemoprotein oxygenases involved in natural product synthetic pathways. Cyanobacteria are oxygenic photosynthetic microorganisms and are considered a rich source of natural products, and are now known to harbour P450s. A variety of cyanobacterial species have been found to contain multiple copies of P450s in their genomes, and over 100 have been predicted. Interestingly, some are membrane-bound as in eukaryotes, as opposed to cytoplasmic in bacteria. Furthermore, they can complement plant P450s and perform bioremediation of oil spills by the breakdown of alkanes. Functional expression of a selection Nostoc spp. P450s in Escherichia coli, with associated enzymes, has successfully produced the sesquiterpenes--germacradienol, germacrene and B-elemene, although others have failed for undetermined reasons. PMID- 20299275 TI - Near-infrared spectroscopy quantitative determination of pefloxacin mesylate concentration in pharmaceuticals by using partial least squares and principal component regression multivariate calibration. AB - Pefloxacin mesylate, a broad-spectrum antibacterial fluoroquinolone, has been widely used in clinical practice. Therefore, it is very important to detect the concentration of Pefloxacin mesylate. In this research, the near-infrared spectroscopy (NIRS) has been applied to quantitatively analyze on 108 injection samples, which was divided into a calibration set containing 89 samples and a prediction set containing 19 samples randomly. In order to get a satisfying result, partial least square (PLS) regression and principal components regression (PCR) have been utilized to establish quantitative models. Also, the process of establishing the models, parameters of the models, and prediction results were discussed in detail. In the PLS regression, the values of the coefficient of determination (R(2)) and root mean square error of cross-validation (RMSECV) of PLS regression are 0.9263 and 0.00119, respectively. For comparison, though applying PCR method to get the values of R(2) and RMSECV we obtained are 0.9685 and 0.00108, respectively. And the values of the standard error of prediction set (SEP) of PLS and PCR models are 0.001480 and 0.001140. The result of the prediction set suggests that these two quantitative analysis models have excellent generalization ability and prediction precision. However, for this PFLX injection samples, the PCR quantitative analysis model achieved more accurate results than the PLS model. The experimental results showed that NIRS together with PCR method provide rapid and accurate quantitative analysis of PFLX injection samples. Moreover, this study supplied technical support for the further analysis of other injection samples in pharmaceuticals. PMID- 20299272 TI - Preparing an oncolytic poliovirus recombinant for clinical application against glioblastoma multiforme. AB - PVS-RIPO is a genetically recombinant, non-pathogenic poliovirus chimera with a tumor-specific conditional replication phenotype. Consisting of the genome of the live attenuated poliovirus type 1 (Sabin) vaccine with its cognate IRES element replaced with that of human rhinovirus type 2, PVS-RIPO displays an inability to translate its genome in untransformed neuronal cells, but effectively does so in cells originating from primary tumors in the central nervous system or other cancers. Hence, PVS-RIPO unleashes potent cytotoxic effects on infected cancer cells and produces sustained anti-tumoral responses in animal tumor models. PVS RIPO presents a novel approach to the treatment of patients with glioblastoma multiforme, based on conditions favoring an unconventional viral translation initiation mechanism in cancerous cells. In this review we summarize advances in the understanding of major molecular determinants of PVS-RIPO oncolytic efficacy and safety and discuss their implications for upcoming clinical investigations. PMID- 20299276 TI - In situ monitoring of pH titration by Raman spectroscopy. AB - Molecular speciation of organic compounds in solution is essential for the understanding of ionic complexation. The Raman technique was chosen because it allows the identification of compounds in different states, and it can give information about the molecular geometry from the analysis of the vibrational spectra. The effect of pH on organic compounds can give information about the ionisation of molecule species. In this study the ionisation steps of salicylic acid and paracetamol have been studied by means of potentiometry coupled with Raman spectroscopy at 30.0 degrees C in a solution of ionic strength 0.96moldm( 3) (KNO(3)) and 0.04moldm(-3) (HNO(3)). The protonation and deprotonation behaviour of the molecules were studied in different pH regions. The abundance of the three different species in the Raman spectra of aqueous salicylic acid have been identified satisfactorily, characterised, and determined by numeric treatment of the data using a multiwavelength curve-fitting program and confirmed with the observed spectral information. PMID- 20299277 TI - Luminescence properties of [Ru(bpy)(2)MDHIP](2+) modulated by the introduction of DNA, copper(II) ion and EDTA. AB - The luminescence properties of [Ru(bpy)(2)MDHIP](2+) (bpy=2,2'-bipyridine, MDHIP=2,4-dihydrophenyl-imidazo[4,5-f][1,10]phenanthroline) in the absence and presence of DNA modulated by the introduction of Cu(2+) ion and EDTA have been investigated. It is found that the ruthenium(II) complex can insert and stack between the base pairs of calf thymus DNA with MDHIP ligand, and the intramolecular hydrogen bond is located inside of the DNA. The presence of DNA can enhance the luminescence intensities of [Ru(bpy)(2)MDHIP](2+) both in buffer solution and on an ITO surface. Moreover, the luminescence intensities of [Ru(bpy)(2)MDHIP](2+) and DNA-bound [Ru(bpy)(2)MDHIP](2+) are quenched by Cu(2+), and next recovered by the addition of EDTA. The repetitive luminescence modulations have been achieved through the introduction of equimolar Cu(2+) and EDTA, respectively. In addition, it becomes evident that the number of luminescence-modulation cycles for [Ru(bpy)(2)MDHIP](2+) in the absence and presence of DNA is influenced by the cumulative concentrations of CuEDTA, generated successively by the strong coordination of Cu(2+) to EDTA. PMID- 20299278 TI - Temperature dependent Raman study of S(B)-->S(C) transition in liquid crystalline compound N-(4-n-pentyloxybenzylidene)-4'-heptylaniline (5O.7). AB - Temperature dependent Raman study of C-H in-plane bending mode ( approximately 1163cm(-1) and approximately 1190cm(-1)) and C-C stretching mode of phenyl ring ( approximately 1571cm(-1) and approximately 1594cm(-1)) of N-(4-n pentyloxybenzylidene)-4'-heptylaniline (5O.7) has been done. Vibrational assignment and potential energy distribution (PED) of individual modes have been calculated employing density functional theory (DFT) for the first time. The S(B) ->S(C) transition is nicely depicted in the variation of the linewidth of the approximately 1163cm(-1) band and the peak position of approximately 1594cm(-1) band with temperature. Because of a small amount of charge density transfer from the core part to the alkyl chain region, the approximately 1163cm(-1) band shifts towards lower wavenumber side whereas the approximately 1190cm(-1) band towards higher wavenumber side at S(B)-->S(C) transition. The approximately 1571cm(-1) and approximately 1594cm(-1) bands are assigned as 8a and 8b modes, whose relative intensity variation with temperature gives the evidence of increased possibility of C-H bending motion of the linking group and the C-C stretching of the alkyl chain in S(C) phase. PMID- 20299279 TI - Growth of gamma glycine crystal and its characterisation. AB - Single crystal of gamma-glycine, an organic nonlinear optical material, has been grown by solvent evaporation technique from a mixture of aqueous solutions of glycine and potassium nitrate, lithium nitrate at room temperature. Gamma glycine crystals have been grown up to the dimension of 20mmx15mmx12mm. Powder X-ray diffraction of the grown crystal was recorded and indexed. Single crystal X-ray diffraction studies were carried out and the unit cell parameters were compared with the literature values. The gamma-phase of glycine is confirmed by single crystal XRD and FTIR spectral analysis. The crystals were characterised by UV-vis NIR transmission spectrum in the range 200-1100nm. The second harmonic generation conversion efficiency of gamma-glycine crystal was twice the efficiency of KDP crystal. Thermal characteristics of gamma-glycine crystals were determined by thermogravimetric analysis (TGA) and differential thermal analysis, which shows the thermal stability of the grown crystals. Dielectric constant and dielectric loss measurements were carried out at different temperatures and frequencies. The microhardness of the grown crystals has been studied using Vicker's microhardness tester. PMID- 20299280 TI - Determination of ofloxacin and gatifloxacin by mixed micelle-mediated cloud point extraction-fluorimetry combined methodology. AB - A cloud point extraction process using mixed micelle of the anionic surfactant sodium dodecyl sulfate (SDS) and the non-ionic surfactant polyoxyethylene(7.5)nonylphenylether (PONPE 7.5) to extract two fluoroquinolone antimicrobial agents, ofloxacin and gatifloxacin, from aqueous media was investigated. The method is based on the mixed micelle-mediated extraction of fluoroquinolones in the presence of NaCl as an inducing agent in phase separation, followed by spectrofluorimetric determination. The effect of different variables such as pH, PONPE7.5 concentration, SDS concentration, NaCl concentration, cloud point temperature, and time was investigated, and optimum conditions were established. At optimum conditions, the rectilinear calibration graphs were obtained in the concentration range of 0.1-150 and 0.1-250ngmL(-1) for ofloxacin and gatifloxacin, and the limits of detection were 0.04 and 0.06ngmL(-1), respectively. The proposed procedure was applied successfully for the detection of the investigated drugs in their pharmaceutical dosage forms, in spiked plasma, spiked urine, and urine samples, with good precision and accuracy. PMID- 20299281 TI - Molecular interaction of organic dyes in bulk and confined media. AB - Molecular interactions of five thiazine dyes with increasing alkyl substitution have been studied in aqueous and microemulsion media at 303K within a concentration range of (1.35-7.00)x10(-4)M. The dimerization constant (K(d)) values for the five dyes are ranged between 1.761 and 6.258x10(3)lmol(-1) in bulk water media, where as in microemulsion media, K(d)'s are ranged between 1.760 and 4.110x10(3)lmol(-1). Thionine (with no methyl substitution) and azure A (with two methyl substitution) displayed slightly larger K(d) values in microemulsion water pools compared to bulk water while other dyes recorded significant drop in K(d) values. The influence of microemulsion media on the molecular interaction of dyes has been explained in terms of electrostatic and hydrophobic factors. The monomer and the dimer spectra are explained in terms of molecular exciton model and the optical absorption parameters of both the species are reported in bulk and confined media. PMID- 20299282 TI - FT-IR, FT-Raman, NMR spectra and DFT calculations on 4-chloro-N-methylaniline. AB - In this work, the vibrational spectral analysis was carried out by using FT-IR and FT-Raman spectroscopy in the range 400-4000 and 50-3500cm(-1) respectively, for the title molecule. The structural and spectroscopic data of the molecule in the ground state were calculated by using density functional method using 6 311++G(d,p) basis set. The vibrational frequencies were calculated and scaled values were compared with experimental FT-IR and FT-Raman spectra. The observed and calculated frequencies are found to be in good agreement. The complete assignments of all the vibrational mode were performed on the basis of the total energy distributions (TED). (13)C and (1)H NMR chemical shifts results were given and are in agreement with the corresponding experimental values. The theoretically constructed FT-IR and FT-Raman spectra exactly coincides with experimental one. PMID- 20299283 TI - Depression in advanced cancer. AB - PURPOSE: Depression is one of the most common psychiatric diseases seen in patients with advanced cancer. It is not only an independent predictor of poor survival in advanced cancer but also reduces quality of life, reduces compliance with treatment and prolongs hospitalization. Yet all too often depression is under diagnosed and under treated in this population. METHOD: A literature review was undertaken using extensive electronic and hand searches. KEY FINDINGS: Whilst it is true that the diagnostic and treatment challenges facing healthcare professionals in this area are considerable one must not forget that depression in advanced cancer is treatable and validated assessment tools have been developed to facilitate diagnosis. CONCLUSIONS: This review article provides the reader with a comprehensive review of the current evidence in this field with particular focus on assessment and treatment. Depression is under diagnosed and under treated - there are valid screening and assessment tools available which will allow appropriate management of this important and debilitating symptom. PMID- 20299284 TI - Knowledge, attitudes and beliefs of Cypriot nurses on the handling of antineoplastic agents. AB - BACKGROUND: Antineoplastic agents have been associated with major concerns among health professionals. The objective of our study was to evaluate the knowledge, attitudes and beliefs of Cypriot nurses on their exposure to antineoplastic agents. METHODS: A cross-sectional survey using a self-administered questionnaire was distributed among oncology nurses in three hospitals in Nicosia. The questionnaire was originally compiled by Turk et al., in order to evaluate the knowledge, attitudes and safe behaviours of nurses' handling cytotoxic drugs and was translated from Turkish to Greek by two bilingual volunteers. RESULTS: A total of 88 nurses participated in the survey (20 male and 68 female). The mean age of the nurses was 33 years (age range 21-60). The majority of nurses were aware of the potential hazards associated with handling of chemotherapy. The mean score of the participants' knowledge was 79.43 out of 100. Most of the participants reported high levels of compliance with the use of personal protective equipment such as gloves and protective gown (95.4%, and 84.5%) during reconstitution of antineoplastic agents, respectively. Almost all nurses (98.8%) reported use of a safety cabinet during preparation, however only 53.4% reported that they have annual medical checkups and only 33% reported having received specialized training. CONCLUSION: While the level of knowledge about antineoplastic agents is high among nurses, along with the level of personal protective equipment use, medical surveillance and employee training seems to be lagging behind. Further research may help us identify the reasons for such discrepancy. PMID- 20299285 TI - Towards a framework for community engagement in global health research. AB - New technologies for global public health are spurring critical evaluations of the role of communities in research and what they receive in exchange for their participation. Community engagement activities resulting from these evaluations are most challenging for novel scientific ventures, particularly those involving controversial strategies and those in which some risks are poorly understood or determined. Remarkably, there is no explicit body of community engagement knowledge to which researchers can turn for guidance about approaches that are most likely to be effective in different contexts, and why. We describe here a framework that provides a starting point for broader discussions of community engagement in global health research, particularly as it relates to the development, evaluation and application of new technologies. PMID- 20299286 TI - The effects of a cardiovascular disease prevention program on knowledge and adoption of a heart healthy lifestyle in Jordanian working adults. AB - BACKGROUND: Improving cardiac related knowledge to further healthy lifestyles is the best preventive strategy against coronary heart diseases (CHD). Previous studies revealed a critical shortage in all-around cardiac related knowledge, plus an overall shortage in adopting healthy lifestyle behaviors. AIMS: To evaluate the effectiveness of an education, counseling and behavioral skill building program in Jordanian working adults' knowledge, attitudes, and beliefs about CHD and adoption of a healthy lifestyle. METHODS: A non-equivalent quasi experimental design was used to evaluate the effectiveness of the intervention program that is based on Pender's Health Promotion Model. The Response Questionnaire and HPLP-II were used to measure subjects' knowledge, attitudes, beliefs and adoption of healthy lifestyle. RESULTS: One hundred six subjects completed the posttest questionnaires. Experimental group showed significantly better cardiac related knowledge, better scores for attitudes, and better scores for the health responsibility, nutritional behaviors, interpersonal relationships and total HPLP-II score. Subject's beliefs, physical activity, spiritual growth and stress management were not improved significantly. Men had better scores in beliefs and women had better scores for health responsibility. CONCLUSION: Individual commitment to healthier lifestyles should be encouraged, and researchers have to design and apply more specific interventions that are directed toward improving factors that are not significantly improved through traditional programs. PMID- 20299287 TI - Small scale genetic alterations contribute to increased mutability at the X linked Hprt locus in vivo in Blm hypomorphic mice. AB - BLM, the gene mutated in Bloom syndrome (BS), encodes an ATP-dependent RecQ DNA helicase that is involved in the resolution of Holliday junctions, in the suppression of crossovers and in the management of damaged replication forks. Cells from BS patients have a characteristically high level of sister chromatid exchanges (SCEs), and increased chromosomal aberrations. Fibroblasts and lymphocytes of BS patients also exhibit increased mutation frequency at the X linked reporter gene HPRT, suggesting that BLM also plays a role in preventing small scale genomic rearrangements. However, the nature of such small scale alterations has not been well characterized. Here we report the characterization of Hprt mutations in vivo in Blm hypomorphic mice, Blm(tm1Ches)/Blm(tm3Brd). We found that the frequency of Hprt mutants was increased about 6-fold in the Blm(tm1Ches)/Blm(tm3Brd) mice when compared to Blm(tm3Brd) heterozygous mice or wildtype mice. Molecular characterization of Hprt gene in the mutant clones indicates that many of the mutations were caused by deletions that range from several base pairs to several thousand base pairs. While deletions in BLM proficient somatic cells are often shown to be mediated by direct repeats, all three deletion junctions in Hprt of Blm(tm1Ches)/Blm(tm3Brd) mice were flanked by inverted repeats, suggesting that secondary structures formed during DNA replication, when resolved improperly, may lead to deletions. In addition, single base pair substitution and insertion/deletion were also detected in the mutant clones. Taken together, our results indicated that BLM function is important in preventing small scale genetic alterations. Thus, both large scale and small scale genetic alterations are elevated when BLM is reduced, which may contribute to loss of function of tumor suppressor genes and subsequent tumorigenesis. PMID- 20299288 TI - Sputum and serum calprotectin are useful biomarkers during CF exacerbation. AB - BACKGROUND: Adequate monitoring of cystic fibrosis lung disease is difficult. CF exacerbation offers a unique setting to test the utility of biomarkers in the assessment of changing airways inflammation. We hypothesised that levels of calprotectin in sputum (and serum) would change informatively following treatment of an exacerbation. METHODS: 27 patients with CF were recruited at onset of pulmonary exacerbation. Sputum and serum were collected at the start and end of anti-biotic therapy. Sputum calprotectin, interleukin-8 (IL8), and myeloperoxidase (MPO) were measured, as were serum calprotectin, CRP and vascular endothelial growth factor (VEGF). RESULTS: Sputum calprotectin decreased following treatment of an exacerbation (p<0.05), and was superior to other sputum markers. Serum calprotectin, CRP, and VEGF also decreased significantly (p=0.002, p=0.002, p=0.013 respectively). Serum calprotectin level following treatment had predictive value for time to next exacerbation (p=0.032). CONCLUSIONS: This study demonstrates the superiority of calprotectin (in sputum and serum) as a biomarker of CF exacerbation over better-established markers. PMID- 20299289 TI - An analytical method for the measurement of acid metabolites of tryptophan-NAD pathway and related acids in urine. AB - An analytical method has been developed for the measurements of five urinary acids namely, quinolinic acid, picolinic acid, nicotinic acid, 2-pyridylacetic acid and 3-pyridylacetic acid. The high performance liquid chromatograph electrospray ionization mass spectrometry was operated in positive polarity under selected ion monitoring mode, with a column flow rate of 0.2 ml/min and an injection volume of 20 microl. The method used isotope-labelled picolinic acid (PA-d(4)) and nicotinic acid (NA-d(4)) as internal standards for the quantification. The sample preparation involved parallel use of two different types of mixed-mode solid phase extraction cartridges (Strata-X-AW for the extraction of quinolinic acid, and Strata-X-C for the remaining acids). Quantitative analysis of five target acids in several human and rat urine samples showed that the levels of acids were relatively uniform among rats while larger variations were observed for human samples. PMID- 20299290 TI - Development of a high-throughput LC/APCI-MS method for the determination of thirteen phytoestrogens including gut microbial metabolites in human urine and serum. AB - The investigation into the potential usefulness of phytoestrogens in the treatment of menopausal symptoms requires large-scale clinical trials that involve rapid, validated assays for the characterization and quantification of the phytoestrogenic precursors and their metabolites in biological matrices, as large interindividual differences in metabolism and bioavailability have been reported. Consequently, a new sensitive high-performance liquid chromatography mass spectrometry method (HPLC-MS) for the quantitative determination of thirteen phytoestrogens including their most important gut microbial metabolites (genistein, daidzein, equol, dihydrodaidzein, O-desmethylangolensin, coumestrol, secoisolariciresinol, matairesinol, enterodiol, enterolactone, isoxanthohumol, xanthohumol and 8-prenylnaringenin) in human urine and serum within one single analytical run was developed. The method uses a simple sample preparation procedure consisting of enzymatic deconjugation followed by liquid-liquid extraction (LLE) or solid-phase extraction (SPE) for urine or serum, respectively. The phytoestrogens and their metabolites are detected with a single quadrupole mass spectrometer using atmospheric pressure chemical ionization (APCI), operating both in the positive and the negative mode. This bioanalytical method has been fully validated and proved to allow an accurate and precise quantification of the targeted phytoestrogens and their metabolites covering the lower parts-per-billion range for the measurement of relevant urine and serum levels following ingestion of phytoestrogen-rich dietary supplements. PMID- 20299291 TI - Rapid determination of 25-hydroxy vitamin D3 in swine tissue using an isotope dilution HPLC-MS assay. AB - A rapid method for quantification of 25-hydroxy vitamin D3 in different swine tissues based on isotope dilution HPLC-MS has been developed and validated. Six times deuterated analyte is used as internal standard. The method is fast and can be performed with only 1g sample. Sample preparation for kidney, liver, muscle and spleen requires only homogenisation and extraction with methanol. An additional enzymatic digest is required for skin, and clean-up of the extract by solid-phase extraction (SPE) is used for adipose tissue and skin. The lower limit of detection varies from 1 ng/g (muscle) to 5 ng/g (adipose and skin). The method has been successfully applied to various tissue samples of pigs fed for 119 days either 2000 IU of vitamin D3 or 50 microg of 25-hydroxy vitamin D3 per kg feed. For animals ingesting 25-OH-D3 supplements the highest tissue contents were observed in the skin (24.8+/-3.5 ng/g), followed by kidney (14.2+/-1.5 ng/g), liver and muscle (5.7+/-0.6 ng/g). The 25-OH-D3 content in the skin was significantly higher in animals ingesting 2000 IU/kg of vitamin D3 (39.5+/-13.4 ng/g). Levels in selected tissues of some animals were below the lower limit of quantification. No measurable amounts of 25-OH-D3 were found in spleen, abdominal fat and subcutaneous fat of the animals of both groups as well as in the liver, kidney and muscle of the animals ingesting 2000 IU/kg of vitamin D3. PMID- 20299292 TI - Interferon-alpha 2b quantification in inclusion bodies using reversed phase-ultra performance liquid chromatography (RP-UPLC). AB - Interferon-alpha 2b (IFN-alpha 2b) is a recombinant therapeutic cytokine produced as inclusion bodies using a strain of Escherichia coli as expression system. After fermentation and recovery, it is necessary to know the amount of recombinant IFN-alpha 2b, in order to determine the yield and the load for solubilization, and chromatographic protein purification steps. The present work details the validation of a new short run-time and fast sample-preparation method to quantify IFN-alpha 2b in inclusion bodies using Reversed Phase-Ultra Performance Liquid Chromatography (RP-UPLC). The developed method demonstrated an accuracy of 100.28%; the relative standard deviations for method precision, repeatability and inter-day precision tests were found to be 0.57%, 1.54% and 1.83%, respectively. Linearity of the method was assessed in the range of concentrations from 0.05 mg/mL to 0.5 mg/mL, the curve obtained had a determination coefficient (r(2)) of 0.9989. Detection and quantification limits were found to be 0.008 mg/mL and 0.025 mg/mL, respectively. The method also demonstrated robustness for changes in column temperature, and specificity against host proteins and other recombinant protein expressed in the same E. coli strain. PMID- 20299293 TI - An improved high-performance liquid chromatography-tandem mass spectrometric method to measure atrazine and its metabolites in human urine. AB - We report an improved solid-phase extraction-high-performance liquid chromatography-tandem mass spectrometry method with isotope dilution quantification to measure seven atrazine metabolites in urine. The metabolites measured were hydroxyatrazine (HA), diaminochloroatrazine (DACT), desisopropylatrazine (DIA), desethylatrazine (DEA), desethylatrazine mercapturate (DEAM), atrazine mercapturate (ATZM), and atrazine (ATZ). Using offline mixed mode reversed-phase/cation-exchange solid-phase extraction dramatically increased recovery and sensitivity by reducing the influence of matrix components during separation and analysis. DACT extraction recovery improved to greater than 80% while the other analytes had similar extraction efficiencies as previously observed. Limits of detection were lower than our previous method (0.05-0.19 ng/mL) with relative standard deviations less than 10%. The total runtime was shorter (18 min) than the previous on-line method, thus it is suitable for large scale sample analyses. We increased the throughput of our method twofold by using the newer extraction technique. PMID- 20299294 TI - Non-Alcoholic Fatty Liver Disease (NAFLD): new challenge for general practitioners and important burden for health authorities? AB - Non-alcoholic fatty liver disease (NAFLD) is the most common cause of hepatic dysfunction encountered in general practice. A large proportion of individuals with type 2 diabetes and the metabolic syndrome develop NAFLD. NAFLD is associated with severe insulin resistance and increased risk of cardiovascular disease and can progress to non-alcoholic steato-hepatitis, liver cirrhosis and cancer. Currently the only known effective treatments for NAFLD are lifestyle changes including stable weight loss and a diet low in calories. General practitioners will increasingly play a key role in dealing with this evolving but serious epidemic of NAFLD and associated metabolic complications. However, success will depend on the appropriate systems and mechanisms being in place in primary care and the proper motivation, support and education of the patient. This review provides the primary care physician with: (a) a step-by step guide of how to identify NAFLD, (b) information to exclude common other causes of liver fat accumulation and (c) additional insight into relationships between NAFLD and other conditions such as obesity, cardiovascular disease and type 2 diabetes. PMID- 20299295 TI - Retrospective analysis of an implantable loop recorder for evaluation of syncope, collapse, or intermittent weakness in 23 dogs (2004-2008). AB - OBJECTIVES: Cardiac arrhythmias as a cause of syncope, collapse, or intermittent weakness can be challenging to diagnose. The purpose of this paper is to retrospectively review the diagnosis and outcome of 23 cases of syncope or collapse in dogs that had a Reveal Plus ILR recorder placed as part of the diagnostic evaluation. ANIMALS, MATERIALS AND METHODS: Medical records of 23 client-owned dogs that were presented for evaluation of syncope, collapse, or intermittent weakness were retrospectively reviewed. RESULTS: Recurrent syncope occurred in 13/23 (57%) and a positive diagnosis of the cause of the event was made in 11/13 (48% of all dogs). Diagnoses included 6/11 with prolonged periods of sinus arrest with slow ventricular escape rate and one each of sub-optimal fixed heart rate by endocardial pacing, high grade second degree atrioventricular block, supraventricular tachycardia, normal ECG during multiple episodes, and high grade second degree atrioventricular block or sinus arrest. CONCLUSIONS: The Reveal Plus ILR device was successful in diagnosing a high percentage of cases of syncope or collapse in which signs recurred and implantation had a low complication rate. The Reveal Plus ILR device is a useful tool to diagnose the etiology of recurrent syncope, collapse, or intermittent weakness in the dog. PMID- 20299296 TI - [Kidney removal and transplant from a living donor. Formal recommendations from the experts. Short text]. PMID- 20299297 TI - [Acute renal failure caused by renal lymphoma. A case report]. AB - Acute renal failure, as the initial manifestation of lymphoma, has been reported only in a few cases. In this work, we report the case of a 28-year-old women admitted for acute renal failure. Her physical examination detected bilateral kidney enlargement. Laboratory evaluation revealed a serum creatinine value 218 micromol/l. A 24-hour urine collection analysis allowed the detection of 1g of protein. No red cells were found after urinanalysis. Renal ultrasound showed massively enlarged kidneys. Renal biopsy of the kidney and pathologic examination showed diffuse infiltration of the interstitium with lymphocytes and atypical cells positive for CD20 markers. A diagnosis of diffuse large B-cell type non Hodgkin lymphoma was made. However, investigations revealed the presence of two others sites of lymphoma: gastric and ophthalmic. The patient's renal function and kidney size as well as the other lymphoma locations were normalized after the initiation of chemotherapy. PMID- 20299298 TI - [Analysis of hemodialysis and graft representations in patients with chronic renal failure: an anthropological approach]. AB - Hemodialysis and kidney transplant are two treatments for renal failure, which lead to numerous changes in the patients' way of life. We have questioned ourselves on the different ways they could deal with those changes by studying the representations and the ritualisation that surrounds the sick. From 2005 to 2007, qualitative interviews, based on the method of life stories, were conducted with 35 patients with chronic renal failure in three Aquitaine's centres. The results show three main groups of representation both in pre-transplant and in post-transplant. Specific behaviours are tied to each group of representation that are beneficial or deleterious with respect to treatment or the patient's social life. We will show that, on the one hand, the patients who see the hemodialysis treatment as a traditional rite of passage cope with the situation more easily and on the other hand, we will stress that this representation is closely linked to how the patients will later accept the kidney transplant. So, we have been able to link the representations of hemodialysis patients and transplant experience. Then these results have a practical consequence for the caregivers who can use the tools of anthropology (the interview guide, analysis grid) through a program of therapeutic education, to precociously take care of patients who are likely to come up against issues after their kidney transplant. PMID- 20299299 TI - Factors that positively influence breastfeeding duration to 6 months: a literature review. AB - QUESTION: What modifiable factors positively influence breastfeeding duration to 6 months postpartum? AIM: This question was posed in order to be able to develop a midwifery intervention aimed at prolonging breastfeeding. METHOD: An online literature search was conducted in Medline, CINAHL, Maternity and Infant Care, and Cochrane Database of systematic reviews. The search strategy included the following keywords: breastfeeding, duration, initiation, cessation, factors, intervention, education, partner, intention, confidence, self-efficacy and support. Additional studies were located and extracted from online publications of New South Wales Department of Health, Australia. Bio-psycho-social factors that are positively associated with breastfeeding duration were identified. RESULTS: Modifiable factors that influence women's breastfeeding decisions are: breastfeeding intention, breastfeeding self-efficacy and social support. Existing midwifery breastfeeding promotion strategies often include social support but do not adequately address attempts to modify breastfeeding intention and self efficacy. CONCLUSION: The modifiable factors that are positively associated with breastfeeding duration are the woman's breastfeeding intention, her breastfeeding self-efficacy and her social support. Intervention studies to date have focussed on modifying these factors individually with variable results. No interventional studies have been conducted with the aim of positively modifying all three factors simultaneously. PMID- 20299300 TI - The indeterminate adrenal lesion. AB - With the increasing use of abdominal cross-sectional imaging, incidental adrenal masses are being detected more often. The important clinical question is whether these lesions are benign adenomas or malignant primary or secondary masses. Benign adrenal masses such as lipid-rich adenomas, myelolipomas, adrenal cysts and adrenal haemorrhage have pathognomonic cross-sectional imaging appearances. However, there remains a significant overlap between imaging features of some lipid-poor adenomas and malignant lesions. The nature of incidentally detected adrenal masses can be determined with a high degree of accuracy using computed tomography (CT) and magnetic resonance imaging (MRI) alone. Positron emission tomography (PET) is also increasingly used in clinical practice in characterizing incidentally detected lesions. We review the performance of the established and new techniques in CT, MRI and PET that can be used to distinguish benign adenomas and malignant lesions of the adrenal gland. PMID- 20299301 TI - Extrarenal malignant rhabdoid tumors: radiologic findings with histopathologic correlation. AB - Extrarenal malignant rhabdoid tumors (MRT) are extremely rare. There have been only a few cases of MRT described in the literature and even fewer in the radiology literature. We present rare uterine and hepatic MRT and their computed tomography, magnetic resonance, and ultrasound imaging features with histopathologic correlation. Although the final diagnosis is based largely on histopathology, radiologists should include MRT in their differential considerations, regardless of tumor location, when they are dealing with an extremely aggressive tumor of early childhood. PMID- 20299302 TI - FDG-PET/CT findings of a metastatic pituitary tumor. AB - The authors report the fluorodeoxyglucose (FDG)-positron emission tomography(PET)/computed tomography (CT) findings of a rare case of growth hormone-secreting pituitary carcinoma with multiple metastatic lesions to the skeleton. A 31-year-old male had presented with acromegaly and had received transsphenoidal resection of a pituitary tumor and adjuvant radiotherapy. However, the tumor recurred with local invasions and the patient underwent more resections and adjuvant chemotherapy. Several months later, the patient developed rising levels of insulin-like growth factor 1 and whole-body FDG-PET/CT scanning revealed multiple hypermetabolic lesions throughout the skeleton compatible with metastasis. PMID- 20299303 TI - Arsenic inhibits myogenic differentiation and muscle regeneration. AB - BACKGROUND: The incidence of low birth weights is increased in offspring of women who are exposed to high concentrations of arsenic in drinking water compared with other women. We hypothesized that effects of arsenic on birth weight may be related to effects on myogenic differentiation. OBJECTIVE: We investigated the effects of arsenic trioxide (As2O3) on the myogenic differentiation of myoblasts in vitro and muscle regeneration in vivo. METHODS: C2C12 myoblasts and primary mouse and human myoblasts were cultured in differentiation media with or without As2O3 (0.1-0.5 microM) for 4 days. Myogenic differentiation was assessed by myogenin and myosin heavy chain expression and multinucleated myotube formation in vitro; skeletal muscle regeneration was tested using an in vivo mouse model with experimental glycerol myopathy. RESULTS: A submicromolar concentration of As2O3 dose-dependently inhibited myogenic differentiation without apparent effects on cell viability. As2O3 significantly and dose-dependently decreased phosphorylation of Akt and p70s6k proteins during myogenic differentiation. As2O3 induced inhibition in myotube formation and muscle-specific protein expression was reversed by transfection with the constitutively active form of Akt. Sections of soleus muscles stained with hematoxylin and eosin showed typical changes of injury and regeneration after local glycerol injection in mice. Regeneration of glycerol-injured soleus muscles, myogenin expression, and Akt phosphorylation were suppressed in muscles isolated from As2O3-treated mice compared with untreated mice. CONCLUSION: Our results suggest that As2O3 inhibits myogenic differentiation by inhibiting Akt-regulated signaling. PMID- 20299305 TI - Histopathological features of acquired dermal melanocytosis. AB - Acquired dermal melanocytosis (ADM) is the term used for pigmentary disorders characterized by blue brown macules, most frequently seen on the face (acquired bilateral nevus of Ota-like macules, ABNOM), and rarely found on the trunk or extremities. Although extrafacial ADM and ABNOM are not usually considered separate entities because of similar features, there has been debate as to whether extrafacial ADM and ABNOM might be part of the same disease spectrum, with or without the same pathogenesis. In order to investigate the relationship between these two entities, the histopathological features of extrafacial ADM and ABNOM were evaluated. We examined nine cases of extrafacial ADM and ten cases of ABNOM. Biopsies were performed on both normal and lesional skin, or on lesional skin only. The sections were stained using hematoxylin-eosin, Fontana-Masson, and NKI/beteb. There was no difference in the degree of melanin pigmentation and the number of melanocytes per unit area in the lesional skin of the epidermis and dermis in the comparisons between extrafacial ADM and ABNOM. The mean depth of the dermal melanocytes was significantly increased in extrafacial ADM (0.88 +/- 0.19 mm) compared to ABNOM (0.58 +/- 0.19 mm); however, in both extrafacial ADM and ABNOM, dermal melanocytes were distributed from the upper to the mid dermis. In conclusion, there was no significant difference in the histopathological features, including relative depth of melanocytes, between extrafacial ADM and ABNOM. To the best of our knowledge, this is the first study to demonstrate by histopathology that extrafacial ADM is the same as ABNOM. PMID- 20299306 TI - Steatocystoma multiplex, a rare distribution of a rare disease. PMID- 20299304 TI - Polychlorinated biphenyls disrupt intestinal integrity via NADPH oxidase-induced alterations of tight junction protein expression. AB - BACKGROUND: Polychlorinated biphenyls (PCBs) are widely distributed environmental toxicants that contribute to numerous disease states. The main route of exposure to PCBs is through the gastrointestinal tract; however, little is known about the effects of PCBs on intestinal epithelial barrier functions. OBJECTIVE: The aim of the present study was to address the hypothesis that highly chlorinated PCBs can disrupt gut integrity at the level of tight junction (TJ) proteins. METHODS: Caco 2 human colon adenocarcinoma cells were exposed to one of the following PCB congeners: PCB153, PCB118, PCB104, and PCB126. We then assessed NAD(P)H oxidase (NOX) activity and expression and the barrier function of Caco-2 cells. In addition, the integrity of intestinal barrier function and expression of TJ proteins were evaluated in C57BL/6 mice exposed to individual PCBs by oral gavage. RESULTS: Exposure of Caco-2 cells to individual PCB congeners resulted in activation of NOX and increased permeability of fluorescein isothiocyanate (FITC) labeled dextran (4 kDa). Treatment with PCB congeners also disrupted expression of TJ proteins zonula occludens-1 (ZO-1) and occludin in Caco-2 cells. Importantly, inhibition of NOX by apocynin significantly protected against PCB mediated increase in epithelial permeability and alterations of ZO-1 protein expression. Exposure to PCBs also resulted in alterations of gut permeability via decreased expression of TJ proteins in an intact physiological animal model. CONCLUSIONS: These results suggest that oral exposure to highly chlorinated PCBs disrupts intestinal epithelial integrity and may directly contribute to the systemic effects of these toxicants. PMID- 20299307 TI - Long-term oral azithromycin in chronic plaque psoriasis: a controlled trial. AB - Continued sub-clinical streptococcal infection might be responsible for chronic plaque psoriasis. Considering the beneficial effect of benzathine penicillin in chronic plaque psoriasis, but due to the risk of penicillin sensitivity and to its painful parenteral route of administration, we tried oral azithromycin in this single blind randomized case-control trial. 50 patients with moderate to severe chronic plaque psoriasis were enrolled. Of these, 30 randomly selected patients received azithromycin for 48 weeks as a single oral 500 mg daily dose for 4 days with a gap of 10 days (total 24 such courses). The remaining 20 patients received a vitamin C tablet (non-chewable) in the same dosage schedule. Informed consent was obtained from all patients enrolled. Though the trial concluded at 48 weeks, patients in the azithromycin-arm were followed for another year to observe any relapse. A significant improvement in PASI score was noted from 12 weeks in the majority of patients in the azithromycin group. At the end of 48 weeks, 18 patients (60%) showed excellent improvement, while 6 patients (20%) showed good improvement and 4 patients (13.33%) showed mild improvement. PASI 75 was 80%. No significant change was seen in lesions in the control group. 2 patients in the study group and 5 patients in the control group did not complete the prescribed duration of study. An exacerbation in lesions was reported in 5 cases (16.66%) in the group receiving azithromycin. These exacerbations also responded by continuing the same treatment. At the end of another one year follow up in the azithromycin-arm, 6 patients (20%) developed a recurrence of lesions. Relevant investigations and clinical assessments were done at regular intervals to observe any side-effects and to check progress of the disease. Data were analysed statistically by using the student t-test. Patients tolerated the therapy well. PMID- 20299308 TI - Evaluation of local anesthesia and pain control in dermatological surgery: a prospective study of 120 patients. AB - Local anaesthesia with lidocaine is widely used in dermatology. The aim of this study was to evaluate pain at different times of dermatological surgery when using local anaesthetic agents. 120 consecutive patients were included during a 3 month period in a dermatological day surgery unit. Pain was estimated by a visual analogue scale, before, during and at the end of the operation. At the end, patients were asked about their satisfaction with local anaesthesia or their preference for general anaesthesia. Fifty five patients had lesions on the face and neck. Other localisations were chest (20 cases), limbs (24 cases), perineum (18 cases) and not recorded in 3 cases. Mean diameter of the lesions was 25.3 mm. Pain occurred during anaesthetic injection in 88.5% of the patients and the score was 5 or more in 42 patients. No pain was recorded during and at the end of the operation in 112 and 118 patients respectively. Fifteen patients would have preferred general to local anaesthesia because of intense pain. Local anaesthesia was judged appropriate by 86% of the patients. However, for lesions of the perineum, general anaesthesia would have been preferred by 38.8% of the patients. PMID- 20299309 TI - Study of fibroblast gene expression in response to oxidative stress induced by hydrogen peroxide or UVA with skin aging. AB - The skin aging process, implying oxidative stress, is associated with specific gene expression. Ultraviolet A (UVA) and hydrogen peroxide (H(2)O(2)) both generate reactive oxygen species (ROS) making them relevant in the study of skin cell responses to oxidative stresses. To investigate transcript expression associated with chronological skin aging and its modulation by two oxidative stresses, cDNA micro-arrays, composed of a set of 81 expressed sequence tag (EST) clones, were used to probe the patterns of transcript expression in human fibroblasts of five young (< 21 years-old) and five older (> 50 years-old) healthy females at basal levels and 24 h after exposure to UVA (7 J/cm2) and H(2)O(2) (20 mM). At the basal state, 22% of total genes were up-regulated in the older group. Although both stresses led to the same cell mortality, H(2)O(2) induced a stronger modulation of gene expression than UVA, with 19.5% of transcripts up-regulated versus 4%. The aging process affected the response to H(2)O(2) and even though cells from old donors presented higher basal levels of transcripts they were not able to regulate them in response to the stress. Interestingly, UVA had a specific strong inhibitory effect on the expression of chemokine (C-C) motif ligand 2 (CCL2) transcript, suggesting a possible mechanism for its anti-inflammatory and immunoregulatory roles. PMID- 20299310 TI - Lichenoid exanthema mimicking graft-versus-host disease associated with obstructive lung disease in a non-transplanted patient. AB - Lichenoid graft-versus-host disease (GVHD) is commonly observed in patients who have received donor lymphocyte infusions or allogeneic bone marrow transplantation (BMT). Here we report a striking case of lichenoid GVH-like exanthema in a young woman without any history of blood transfusions or BMT. A polymorphous, multiforme-like exanthema was observed after systemic antibiotic therapy of bronchitis and was initially diagnosed as drug eruption. Later on, disseminated lichenoid papules were noticed on the trunk and extremities with all histologic and clinical characteristics of lichenoid GVHD. Cutaneous GVH-like disease developed, as did obstructive lung disease. Pulmonary as well as skin disease were both refractory to various immunosuppressive therapies. The immune pathogenesis that caused the skin and lung disease in this patient remains unclear. Multiple pregnancies with two abortions with the potential induction of microchimerism may play a role in the disease pathogenesis. PMID- 20299311 TI - Acrodermatitis chronic atrophicans and morphea. PMID- 20299312 TI - Carcinosarcoma of the nose. PMID- 20299313 TI - Condyloma accuminata-like hypertrophic lichen planus. PMID- 20299314 TI - Morphea, an unusual side effect of anti-TNF-alpha treatment. PMID- 20299315 TI - Chinese herbal medicine: a neglected offender for fixed drug eruptions. PMID- 20299316 TI - Phase III trials of eribulin mesylate (E7389) in extensively pretreated patients with locally recurrent or metastatic breast cancer. AB - Eribulin mesylate (E7389) is a nontaxane microtubule dynamics inhibitor with a novel mechanism of action. In preclinical studies, it has activity in a variety of in vivo tumor model types, including breast cancer. Following promising results from phase I and phase II studies in patients with breast cancer, 2 open label, randomized, controlled, parallelgroup phase III studies have been initiated, and enrollment has been completed. Both study populations comprise patients with locally advanced/recurrent or metastatic disease pretreated with several chemotherapy regimens, including an anthracycline and a taxane. In Study 305, eribulin is being evaluated as late-line therapy. The primary objective is to compare overall survival (OS) between eribulin monotherapy and treatment of the physician's choice, and progression-free survival (PFS) is one of the secondary objectives. The 762 patients enrolled in Study 305 were randomized in a 2:1 ratio to receive either eribulin or treatment of the physician's choice. In Study 301, eribulin is being assessed as second-line therapy, and the primary objective is to compare eribulin and capecitabine in terms of OS and PFS. Secondary objectives include assessments of response data, duration of response, quality of life, pain intensity, analgesic consumption, and assessment of pharmacokinetic/pharmacodynamic relationships for eribulin. In Study 301, the 1102 patients enrolled were randomized to receive either eribulin or capecitabine (approximately 550 patients in each arm). Tumor assessments are carried out every 8 weeks in Study 305, and every 2 cycles (each of 3 weeks' duration) in Study 301. Safety is also assessed in both studies. PMID- 20299317 TI - Characteristics, treatment, and outcome of breast cancers diagnosed in BRCA1 and BRCA2 gene mutation carriers in intensive screening programs including magnetic resonance imaging. AB - BACKGROUND: Breast magnetic resonance imaging (MRI) with conventional screening methods improves sensitivity in high-risk patients without benefits on specific survival. We evaluated the characteristics, treatments, and prognostic features of breast cancers diagnosed among BRCA1/2 mutation carriers either inside or outside screening programs that included MRI. PATIENTS AND METHODS: Two groups of patients diagnosed with a new breast cancer between 2001 and 2007 were compared: group 1, patients included in an intensive screening program; and group 2, patients outside of this program. RESULTS: Twenty-one patients met inclusion criteria for group 1, and 102 for group 2. Seventy-four percent and 65%, respectively, were BRCA1 mutation carriers. Tumors in both groups had the same characteristics (pN, grade, estrogen receptor, progesterone receptor, HER2 expression), except for smaller tumor size in group 1 (median, 6 mm vs. 22 mm; P < .0001). Group 1 patients had more frequent sentinel node procedures (57% vs. 28%; P = .021) and less commonly received chemotherapy (43% vs. 86%; P < .0001). The 3-year disease-free survival (93% vs. 74%; P = .1) and the 3-year overall survival (100% vs. 92%; P = .2) did not differ between groups. CONCLUSION: MRI might provide improvement in BRCA1/2 carriers in terms of smaller tumor size and treatment morbidity. However, because of aggressive intrinsic characteristics, this does not turn into significant survival benefits. PMID- 20299318 TI - Breast cancer hormone receptor assay results of core needle biopsy and modified radical mastectomy specimens from the same patients. AB - BACKGROUND: Hormone receptor (HR) expression is the most important biomarker and is the cornerstone in the management of breast cancer. Therefore, the accuracy of its testing is critical in treatment decisions. PATIENTS AND METHODS: A total of 160 consecutive patients accrued to an adjuvant hormonal therapy clinical trial between March 2003 and May 2008 were studied. Estrogen receptor (ER) and progesterone receptor (PgR) protein assays of tissues from modified radical mastectomy (MRM) specimens were compared with their previous core needle biopsy (CNB) ER and PgR immunohistochemical assay results. RESULTS: The tumors of 146 (91.2%) out of the 160 patients with CNB HR-positive disease remained HR positive in MRM specimen assays. Estrogen receptor positivity decreased from 95% in the CNB to 81.9% in MRM specimens and PgR positivity from 93.8% to 86.9%. The overall agreement between CNB and MRM specimens was 81.9% for ER and 85.6% for PgR. The mean Allred scores were significantly higher in CNB than in MRM specimens: ER, 6.6 (SD, 2.02) versus 4.71 (SD, 2.62); PgR, 6.68 (SD, 2.16) versus 5.99 (SD, 2.68); P < .001 and P = .001, respectively. CONCLUSION: Core needle biopsy specimens are associated with the identification of more frequent and higher levels of tumoral hormonal receptor proteins than MRM specimens. Delayed fixation of MRM tissues likely accounted for this finding. Optimal selection of patients for hormonal therapies is dependent on tissue management strategies before formal hormonal receptor protein testing procedures. PMID- 20299319 TI - A phase II trial of pemetrexed and gemcitabine in patients with metastatic breast cancer who have received prior taxane therapy. AB - PURPOSE: This phase II trial assessed efficacy and safety of pemetrexed plus gemcitabine to treat metastatic or locally advanced breast cancer in patients previously treated with taxanes. PATIENTS AND METHODS: Eligible women with advanced breast cancer treated with taxanes in the adjuvant or metastatic setting received pemetrexed 500 mg/m2 on day 1 followed by gemcitabine 1000 mg/m2 on days 1 and 8 of a 21-day cycle. Hematologic toxicities limiting day 8 gemcitabine dosing were observed in the first 20 patients, prompting a protocol amendment to evaluate pemetrexed 500 mg/m2 followed by gemcitabine 1500 mg/m2 on day 1 of a 14 day cycle. Patients received folic acid, vitamin B12, and dexamethasone. The primary endpoint was objective response rate (ORR). RESULTS: Between July 2003 and September 2006, 73 evaluable women (median age, 52.1 years; range, 28-73 years) were enrolled (21-day schedule: 21 patients, 52% estrogen receptor positive, 24% HER2-positive; 14-day schedule: 52 patients, 58% ER-positive, 15% HER2-positive). For patients on the 21-day and 14-day schedules, median number of cycles was 4 (range, 1-8 cycles) and 5 (range, 1-38 cycles), respectively. The ORRs were 23.8% and 19.2%, respectively; median survival times were 16.2 months and 13.4 months. The most common grade 3/4 hematologic toxicities were neutropenia (71% vs. 33%) and leukopenia (24% vs. 14%); febrile neutropenia occurred in 10% and 6%. The most common grade 3/4 nonhematologic toxicity was fatigue (29% vs. 10%). CONCLUSION: Pemetrexed/gemcitabine given on a 21-day or 14 day schedule is active in patients with advanced breast cancer previously treated with taxanes. A 14-day schedule appears to result in fewer serious toxicities. PMID- 20299320 TI - Rheumatic disorders and functional disability with aromatase inhibitor therapy. AB - BACKGROUND: Aromatase inhibitor therapy is often effective for breast cancer, yet it can be accompanied by musculoskeletal pain and stiffness. This prevalence assessment aimed to characterize a rheumatologist's view of frequency and clinical features, including associated disability, within a breast cancer clinic panel of 77 patients. PATIENTS AND METHODS: The "aromatase inhibitor arthralgia" frequency was estimated at 50%, including both those with new and worsened discomfort. Substantial functional disability was associated, whether measured by individual functional disability (frequencies ranging from 39% to 61%) or composite score of 7 functional disability areas (median score 5 compared with median 0 in the comparison group; P = .00003). RESULTS: The frequency of clinical hand osteoarthritis appeared somewhat increased in the aromatase inhibitor arthralgia group (28% vs. 14%; not statistically significant). Yet the distribution of aromatase inhibitor-related symptoms and functional disabilities appeared to parallel those joint regions commonly affected by osteoarthritis. Using clinical criteria to assess 5 common rheumatic disorders (hand osteoarthritis, trigger finger, carpal tunnel syndrome, Raynaud's phenomenon, and sicca syndrome), the aromatase inhibitor arthralgia group tended to have more common rheumatic disorders (P < .05), consistent with nociceptive mechanisms making latent disorders symptomatic. CONCLUSION: Aromatase inhibitor therapy for postmenopausal breast cancer might be associated with common musculoskeletal symptoms and with substantial functional disability and should prompt patient education. In view of the potential relevance of estrogen deprivation to osteoarthritis onset and severity, future studies of natural history should include systematic assessment of osteoarthritis frequency and severity. PMID- 20299321 TI - Evolution of capecitabine dosing in breast cancer. AB - In the United States, poor patient tolerability of the standard capecitabine dosing regimen (1250 mg/m2 twice daily on days 1-14 administered every 21 days) limits the established benefit of the agent. The observation that patient tolerability improves and efficacy is maintained with lower doses led to the investigation of various doses and schedules in patients with metastatic breast cancer. Capecitabine monotherapy in daily doses of 1000-2560 mg/m2 or in combination with a taxane in daily doses of 825-1250 mg/m2 has confirmed that tolerability improves and efficacy is maintained with lower-than-standard doses. Similar results have been observed with various dosing schedules, including continuous administration and 28-day, 7-day, and 7-days-on/7-days-off cycles. These findings suggest that capecitabine administered in a variety of doses and schedules might be a viable alternative to anthracycline-containing regimens as first- or second-line treatment in patients with metastatic breast cancer. PMID- 20299322 TI - Low morale is associated with increased risk of mortality in the elderly: a population-based prospective study (NEDICES). AB - OBJECTIVE: the study aimed to assess the association between morale and mortality. DESIGN: we used data from the Neurological Disorders in Central Spain (NEDICES), a population-based study. SUBJECTS: 2,516 older persons (mean age 75.7 years) participated in the study. METHODS: Cox models were used to estimate risk of mortality. Morale was assessed using the Philadelphia Geriatric Center Morale Scale. RESULTS: 489 (21.8%) participants died over a median follow-up of 5.9 years (range 0.1-7.7 years), including 253 (21.8%) deaths among 1,163 participants with low morale scores, 168 (19.3%) among 870 participants with moderate scores and 68 (14.1%) among participants with high scores. In an unadjusted Cox model, relative risk (RR) of mortality in participants with low morale scores = 1.69 (P < 0.001) and RR in participants with moderate scores = 1.47 (P < 0.01) were compared to the reference group (participants with high scores). In a Cox model that adjusted for a variety of demographic factors and co morbidities, RR of mortality in participants with low morale scores = 1.35 (P <0.05) and moderate scores = 1.16 (not significant) were compared to the reference group. CONCLUSION: low morale may be an independent predictor of mortality in the elderly. By assessing morale, practitioners might be better positioned to identify patients with poorer prognoses. PMID- 20299323 TI - Severe exfoliative dermatitis caused by strontium ranelate: two cases of a new drug reaction. AB - Strontium ranelate is a relatively new drug used as a second-line treatment for osteoporosis, often targeted at older patients. It is known to cause skin rash and rarely drug reaction with eosinophilia and systemic symptoms, but there are no reports of exfoliative dermatitis as a reaction in the literature. We present the first two cases of this adverse effect of the drug, combined with eosinophilia but no systemic symptoms. We illustrate the significant morbidity involved and use of systemic steroid treatment required, highlighting the need for awareness of this reaction in medical and particularly in elderly care communities. PMID- 20299324 TI - SeSAW: balancing sequence and structural information in protein functional mapping. AB - MOTIVATION: Functional similarity between proteins is evident at both the sequence and structure levels. SeSAW is a web-based program for identifying functionally or evolutionarily conserved motifs in protein structures by locating sequence and structural similarities, and quantifying these at the level of individual residues. Results can be visualized in 2D, as annotated alignments, or in 3D, as structural superpositions. An example is given for both an experimentally determined query structure and a homology model. AVAILABILITY AND IMPLEMENTATION: The web server is located at http://www.pdbj.org/SeSAW/. PMID- 20299325 TI - Going from where to why--interpretable prediction of protein subcellular localization. AB - MOTIVATION: Protein subcellular localization is pivotal in understanding a protein's function. Computational prediction of subcellular localization has become a viable alternative to experimental approaches. While current machine learning-based methods yield good prediction accuracy, most of them suffer from two key problems: lack of interpretability and dealing with multiple locations. RESULTS: We present YLoc, a novel method for predicting protein subcellular localization that addresses these issues. Due to its simple architecture, YLoc can identify the relevant features of a protein sequence contributing to its subcellular localization, e.g. localization signals or motifs relevant to protein sorting. We present several example applications where YLoc identifies the sequence features responsible for protein localization, and thus reveals not only to which location a protein is transported to, but also why it is transported there. YLoc also provides a confidence estimate for the prediction. Thus, the user can decide what level of error is acceptable for a prediction. Due to a probabilistic approach and the use of several thousands of dual-targeted proteins, YLoc is able to predict multiple locations per protein. YLoc was benchmarked using several independent datasets for protein subcellular localization and performs on par with other state-of-the-art predictors. Disregarding low-confidence predictions, YLoc can achieve prediction accuracies of over 90%. Moreover, we show that YLoc is able to reliably predict multiple locations and outperforms the best predictors in this area. AVAILABILITY: www.multiloc.org/YLoc. PMID- 20299326 TI - HALO--a Java framework for precise transcript half-life determination. AB - Recent improvements in experimental technologies now allow measurements of de novo transcription and/or RNA decay at whole transcriptome level and determination of precise transcript half-lives. Such transcript half-lives provide important insights into the regulation of biological processes and the relative contributions of RNA decay and de novo transcription to differential gene expression. In this article, we present HALO (Half-life Organizer), the first software for the precise determination of transcript half-lives from measurements of RNA de novo transcription or decay determined with microarrays or RNA-seq. In addition, methods for quality control, filtering and normalization are supplied. HALO provides a graphical user interface, command-line tools and a well-documented Java application programming interface (API). Thus, it can be used both by biologists to determine transcript half-lives fast and reliably with the provided user interfaces as well as software developers integrating transcript half-life analysis into other gene expression profiling pipelines. AVAILABILITY: Source code, executables and documentation are available at http://www.bio.ifi.lmu.de/software/halo. PMID- 20299327 TI - ArchSchema: a tool for interactive graphing of related Pfam domain architectures. AB - ArchSchema is a Java Web Start application that generates a dynamic 2D network of related Pfam domain architectures. Each node corresponds to a different architecture (shown as a sequence of coloured boxes) and indicates whether any 3D structural information is available in the PDB. Satellite nodes can show either the UniProt codes or the PDB codes of proteins having the given architecture. Search options allow search by UniProt code or Pfam domain identifier, and results can be filtered by domain, organism, or by selecting only proteins in the PDB. AVAILABILITY: ArchSchema can be freely accessed at http://www.ebi.ac.uk/Tools/archschema. PMID- 20299328 TI - Interaction of human MCM2-7 proteins with TIM, TIPIN and Rb. AB - Interactions of human MCM2-7 proteins with the proteins of TIM, TIPIN, an amino terminal fragment of Rb, and p27 were examined by co-immuno-precipitation experiment using cell lysates of co-expressed insect cells. TIM and TIPIN, both of which are involved in regulation of DNA replication fork progression, mainly interacted with MCM3-7 proteins. The amino-terminal fragment of Rb, which inhibits DNA replication in Xenopus egg extracts, was able to bind with MCM3 and MCM6 proteins in addition to MCM7 protein. In contrast, p27 was not able to bind any MCM2-7 proteins under the comparable conditions. These results indicate that the proteins, which are known to interact with MCM proteins, bind with MCM2-7 proteins with different affinities and specificities. PMID- 20299329 TI - Development of evaluation system for bioactive substances using human artificial chromosome-mediated osteocalcin gene expression. AB - Bioactive substances in daily food and supplements are expected to prevent various lifestyle-related diseases. Recently, many evaluation systems for bioactive substances were developed with cell lines integrated with green fluorescence protein (GFP) reporter gene. To evaluate osteogensis activity in functional food, we developed a novel cell line that reports osteocalcin gene expression using the human artificial chromosome (HAC) vector. HAC vectors are able to avoid various problems in usual plasmid vector such as difficulty in control of transgene copy number. HAC is transmitted to cells as an independent chromosome from host chromosomes, and expresses transgenes depending on host cell circumstances. We established Chinese hamster ovary cell lines that carried GFP gene regulated by osteocalcin gene promoter on the HAC. Expression of GFP was responded to vitamin D(3) [1alpha,25(OH)(2)D(3)]. Furthermore, we constructed HAC vector bearing tandem repeats of reporter gene unit, to enhance intensity of gene expression. GFP expression in these reporter cells is related to the copy number of reporter gene units. Using the evaluation system for bioactive substances, we could show osteogenic activity in some fish oils. PMID- 20299330 TI - Constitutive glycogen synthase kinase-3alpha/beta activity protects against chronic beta-adrenergic remodelling of the heart. AB - AIMS: Glycogen synthase kinase 3 (GSK-3) signalling is implicated in the growth of the heart during development and in response to stress. However, its precise role remains unclear. We set out to characterize developmental growth and response to chronic isoproterenol (ISO) stress in knockin (KI) mice lacking the critical N-terminal serines, 21 of GSK-3alpha and 9 of GSK-3beta respectively, required for inactivation by upstream kinases. METHODS AND RESULTS: Between 5 and 15 weeks, KI mice grew more rapidly, but normalized heart weight and contractile performance were similar to wild-type (WT) mice. Isolated hearts of both genotypes responded comparably to acute ISO infusion with increases in heart rate and contractility. In WT mice, chronic subcutaneous ISO infusion over 14 days resulted in cardiac hypertrophy, interstitial fibrosis, and impaired contractility, accompanied by foetal gene reactivation. These effects were all significantly attenuated in KI mice. Indeed, ISO-treated KI hearts demonstrated reversible physiological remodelling traits with increased stroke volume and a preserved contractile response to acute adrenergic stimulation. Furthermore, simultaneous pharmacological inhibition of GSK-3 in KI mice treated with chronic subcutaneous ISO recapitulated the adverse remodelling phenotype seen in WT hearts. CONCLUSION: Expression of inactivation-resistant GSK-3alpha/beta does not affect eutrophic myocardial growth but protects against pathological hypertrophy induced by chronic adrenergic stimulation, maintaining cardiac function and attenuating interstitial fibrosis. Accordingly, strategies to prevent phosphorylation of Ser-21/9, and consequent inactivation of GSK-3alpha/beta, may enable a sustained cardiac response to chronic beta-agonist stimulation while preventing pathological remodelling. PMID- 20299331 TI - Mineralocorticoid receptor overexpression in embryonic stem cell-derived cardiomyocytes increases their beating frequency. AB - AIMS: Cardiac mineralocorticoid receptor (MR) activation triggers adverse cardiovascular events that could be efficiently prevented by mineralocorticoid antagonists. To gain insights into the pathophysiological role of MR function, we established embryonic stem (ES) cell lines from blastocysts of transgenic mice overexpressing the human MR driven by its proximal P1 or distal P2 promoter and presenting with cardiomyopathy, tachycardia, and arrhythmia. Cardiomyocyte differentiation allowed us to investigate the molecular mechanisms contributing to MR-mediated cardiac dysfunction. METHODS AND RESULTS: During cardiac differentiation, wild-type (WT) and recombinant ES cell cultures and excised beating patches expressed endogenous MR along with cardiac gene markers. The two fold increase in MR protein detected in P1.hMR and P2.hMR cardiomyocytes led to a parallel increase in the spontaneous beating frequency of hMR-overexpressing cardiomyocytes compared with WT. The MR-mediated chronotropic effect was ligand independent, could be partially repressed by spironolactone, and was accompanied by a significant two- to four-fold increase in mRNA and protein levels of the pacemaker channel HCN1, generating depolarizing If currents, thus revealing a potential new MR target. This was associated with modification in the expression of HCN4, the inward-rectifier potassium channel Kir2.1, and the L-type voltage dependent calcium channel Cav1.2. CONCLUSION: We demonstrate that the amplification of MR signalling in ES-derived cardiomyocytes has a major impact on cardiomyocyte contractile properties through an important remodelling of ion channel expression, contributing to arrhythmias. Our results highlight the prominent role of MR function in cardiac physiology and support the benefit of MR antagonists in the management of cardiac dysfunctions. PMID- 20299332 TI - Natural therapeutic magnesium lithospermate B potently protects the endothelium from hyperglycaemia-induced dysfunction. AB - AIMS: We have investigated the effects of magnesium lithospermate B (MLB), the active compound of the Oriental herbal remedy, Salvia miltiorrhizae, on endothelial dysfunction associated with diabetes mellitus using cultured endothelial cells and an animal model of type 2 diabetes mellitus. METHODS AND RESULTS: The effect of MLB on vasodilatory function in Otsuka Long-Evans Tokushima Fatty (OLETF) rats was assessed. MLB treatment for 20 weeks starting at 12 weeks attenuated the decrease in endothelium-dependent vasodilation in OLETF rats. MLB treatment also increased serum nitrite level and reduced serum advanced glycation end products concentration. The effect of MLB was greater than an equivalent dose of alpha-lipoic acid (alphaLA), a popular antioxidant treatment. MLB rescued the inhibition of endothelial nitric oxide synthase (eNOS) activity and eNOS phosphorylation in endothelial cells cultured in hyperglycaemia. This effect was dependent on Akt phosphorylation and associated with decreased O linked N-acetylglucosamine protein modification of eNOS. MLB also increased nuclear factor erythroid 2-related factor-2 (Nrf-2) activation in a phosphoinositide 3-kinase/Akt pathway dependent manner. MLB treatment induced the expression of the Nrf-2-regulated antioxidant enzyme, heme oxygenase-1. The antioxidant alphaLA could not produce this effect. Moreover, MLB decreased oxidative stress and endothelial cell apoptosis caused by hyperglycaemia. CONCLUSION: MLB is a naturally occurring, new generation antioxidant that activates eNOS and ameliorates endothelial dysfunction in diabetes by enhancing vasodilation in addition to reducing oxidative stress. The relative strong performance of MLB makes it an ideal candidate for further, expanded trials as a new generation of antioxidant to treat diabetes-related complications. PMID- 20299333 TI - Role of blood cells in ischaemia-reperfusion induced endothelial barrier failure. AB - Ischaemia and reperfusion (I/R) elicits an acute inflammatory response that is characterized by the recruitment of inflammatory cells, oxidative stress, and endothelial barrier failure. Over the past three decades, much progress has been made in our understanding of the mechanisms that underlie the inflammatory response and microvascular dysfunction associated with I/R. This review is focused on the role of leucocytes (neutrophils and T-lymphocytes) and platelets, and their activation products, as mediators of I/R-induced endothelial barrier failure. The contributions of cytokines, chemokines, and oxidative stress to I/R induced barrier dysfunction are also discussed. It concludes with an analysis of how risk factors for cardiovascular disease, i.e. hypertension, diabetes, hypercholesterolaemia, and obesity, influence the vascular permeability response to I/R. Areas of uncertainty and controversy in this field of investigation are also identified. PMID- 20299335 TI - Role of GTPases in control of microvascular permeability. AB - Inflammatory mediators increase vascular permeability primarily by formation of intercellular gaps between endothelial cells of post-capillary venules. Under these conditions, endothelial cell-cell contacts such as adherens and tight junctions open to allow paracellular fluid passage. Small guanosine triphosphatases (GTPases) from the ras superfamily, primarily Rho GTPases (RhoA, Rac1, Cdc42) or Rap1 are known to regulate cell adhesion, in part by reorganization of the junction-associated cortical actin cytoskeleton. In this review, we will discuss the role of small GTPases for the maintenance of microvascular barrier functions under resting conditions as well as under conditions of increased permeability and their involvement in signalling pathways downstream of both barrier-stabilizing and inflammatory mediators. Rac1 and Cdc42 are the main GTPases required for barrier maintenance and stabilization, whereas RhoA negatively regulates barrier properties under both resting and inflammatory conditions. For Rac1 and RhoA, contrary functions under certain conditions have also been described. However, Rac1-mediated barrier destabilization in microvascular endothelium appears to be largely restricted to conditions of enhanced endothelial cell migration and thus to be more closely related to angiogenesis rather than to inflammation. Recent studies revealed that cAMP signalling, which is well known to be barrier protective, enhances barrier functions in part via Rap1-mediated activation of Rac1 and Cdc42 as well as by inhibition of RhoA. Moreover, barrier-stabilizing mediators directly activate Rac1 and Cdc42 or increase cAMP levels. On the other hand, several barrier disruptive components appear to increase permeability by reduced formation of cAMP, leading to both inactivation of Rac1 and activation of RhoA. PMID- 20299334 TI - Caveolin-1 limits the contribution of BK(Ca) channel to EDHF-mediated arteriolar dilation: implications in diet-induced obesity. AB - AIMS: Caveolin-1 (Cav-1) interacts with large conductance Ca(2+)-activated potassium channels (BKCa) and likely exerts a negative regulatory effect on the channel activity. We investigated the role of Cav-1 in modulating BK(Ca) channel mediated, endothelium-derived hyperpolarizing factor (EDHF)-dependent arteriolar dilation in normal condition and in an experimental model of obesity. METHODS AND RESULTS: In isolated, pressurized (80 mmHg) gracilis muscle arterioles (approximately 100 microm) of Cav-1 knockout mice, acetylcholine (ACh)-induced, EDHF-mediated dilations were enhanced and were significantly reduced by the BK(Ca) channel inhibitor, iberiotoxin (IBTX), whereas IBTX had no effect on EDHF mediated dilations in the wild-type mice. Dilations to the selective BK(Ca) channel opener, NS-1619 were augmented in the Cav-1 knockout mice. In high-fat diet-treated, obese rats ACh-induced coronary arteriolar dilations were preserved, whereas IBTX-sensitive, ACh-induced and also NS-1619-evoked vasodilations were augmented when compared with lean animals. In coronary arterioles of obese rats a reduced protein expression of Cav-1 was detected by western immunoblotting and immunohistochemistry. Moreover, in coronary arterioles of lean rats, disruption of caveolae with methyl-beta-cyclodextrin augmented IBTX sensitive, ACh-induced, and also NS-1619-evoked dilations. CONCLUSION: Thus, under normal conditions, Cav-1 limits the contribution of the BK(Ca) channel to EDHF-mediated arteriolar dilation. In obesity, a reduced expression of Cav-1 leads to greater contribution of the BK(Ca) channel to EDHF-mediated response, which seems essential for maintained coronary dilation. PMID- 20299336 TI - A 50% reduction in cyclosporine exposure in stable renal transplant recipients: renal function benefits. AB - BACKGROUND: Although cyclosporine maintenance therapy reduces the risk of acute rejection and increases short-term graft survival in renal transplant recipients, its associated nephrotoxicity increases the risk of chronic graft dysfunction. The dose that allows an optimal risk-to-benefit ratio has not been established. METHODS: This multicentre study enrolled stable renal allograft recipients receiving cyclosporine and mycophenolate mofetil without corticosteroids in their second year post-transplant. Patients were randomized to a cyclosporine dose targeted to a standard area under the concentration-time curve (AUC)(0-12 h) (usual exposure, n = 104) or 50% of the study standard AUC(0-12 h) (low exposure, n = 108) using a three-point pharmacokinetic sampling. The primary endpoint was the percentage of patients with treatment failure at 24 months (graft loss/acute rejection/nephrotoxicity/>15% serum creatinine level increase). RESULTS: Treatment failure was reported in 37 out of 101 (37%) patients in the usual exposure and 19 out of 106 (18%) patients in the low-exposure groups (P = 0.003). Mean estimated glomerular filtration rate decreased from baseline to 2 years with usual exposure and increased with low exposure (P < 0.001). Mean systolic and diastolic blood pressures were lower with low exposure (P = 0.03 and P = 0.008, respectively). CONCLUSION: In renal transplant recipients receiving maintenance therapy without corticosteroids, a minimization strategy using three-point pharmacokinetic sampling to reduce and maintain cyclosporine exposure to 50% of the usual levels is safe and reduces the risk of graft dysfunction. PMID- 20299337 TI - Non-invasive detection of pulmonary hypertension prior to renal transplantation is a predictor of increased risk for early graft dysfunction. AB - BACKGROUND: Early graft dysfunction is a significant complication after renal transplantation and is a marker of adverse outcomes. Although multiple predictors of graft dysfunction have been previously described, the reported prevalence of pulmonary hypertension (pulmonary HTN) in the dialysis population (40-50%), along with biologic and physiologic principles, led us to hypothesize that pulmonary HTN might be an additional risk factor for early graft dysfunction. METHODS: We performed a retrospective study that screened all adult renal transplants performed at our institution over a 3-year period and limited the evaluation to those subjects who had an estimated pulmonary artery systolic pressure on a preoperative echocardiogram report (n = 55). The primary outcome of this study was to investigate the impact of pulmonary HTN on early graft dysfunction using a combined endpoint of delayed graft function or slow graft function. RESULTS: Among patients receiving a living donor kidney, early graft dysfunction was not observed regardless of pulmonary HTN status. However, among patients receiving a deceased donor kidney, pulmonary HTN was found to be associated with a significant increased risk of early graft dysfunction (56 vs 11.7%, P = 0.01). Univariate and multivariable logistic regression supported this observation as an independent risk factor beyond potential confounding recipient, donor and graft based risk factors for early graft dysfunction (P < 0.05). CONCLUSION: Pulmonary HTN detected on non-invasive imaging prior to renal transplantation appears to be an independent predictor of early graft dysfunction among those patients who receive a deceased donor kidney. PMID- 20299339 TI - Long-term renal survival in malignant hypertension. AB - BACKGROUND: Some studies have shown an improvement in the prognosis of patients with essential malignant hypertension (MHT), but data about long-term outcome and prognostic factors of these patients are scarce. METHODS: We performed a single centre retrospective analysis of 197 patients with MHT, diagnosed in the period 1974-2007. RESULTS: Incidence of MHT remained stable along the different periods of the study. Renal damage at presentation was common (63% of patients) but renal function improved or remained stable after diagnosis in a majority of patients. The probability of renal survival was 84 and 72% after 5 and 10 years, respectively. Diagnosis during the first period (1974-85) of the study, previous chronic renal impairment, baseline renal function and proteinuria, presence of microhaematuria, systolic and diastolic blood pressure and proteinuria during follow-up were associated with an unfavourable outcome. By multivariate analysis, mean proteinuria during follow-up remained as the only significant risk factor (OR, 2.72; 95% CI, 1.59-4.64). Renal survival for patients with mean proteinuria <0.5 g/24 h was 100 and 95% after 5 and 10 years, respectively. The number of patients who improved or stabilized their renal function significantly increased in the second and third periods of the study (1987-2007). CONCLUSIONS: Renal survival in MHT has improved in recent years. Mean proteinuria during follow-up is a fundamental prognostic factor for renal survival. PMID- 20299338 TI - Outcome predictability of serum alkaline phosphatase in men with pre-dialysis CKD. AB - BACKGROUND: Serum alkaline phosphatase (ALP) increases in patients with chronic kidney disease (CKD) and high-turnover bone disease. ALP may represent an adjunct marker of high bone turnover devoid of drawbacks of serum parathyroid hormone (PTH), and it may also be associated with cardiovascular calcification in CKD. Higher ALP has been recently associated with increased mortality and coronary calcification in dialysis patients. In pre-dialysis CKD patients, this association is not clear. METHODS: We examined the association of baseline, time varying and time-averaged ALP with all-cause mortality and the composite of pre dialysis mortality or end-stage renal disease in a historical prospective cohort of 1158 male veterans with pre-dialysis CKD from a single institution by using multivariable-adjusted Cox models. RESULTS: Higher ALP was associated with increased mortality irrespective of the statistical model. Time-averaged ALP displayed a consistent linear association with mortality: a 50-U/L higher serum ALP was associated with a multivariable-adjusted death hazard ratio (95% confidence interval) of 1.17 (1.08-1.28), P < 0.001. Baseline and time-varying ALP showed non-linear associations with mortality, with serum levels above 70 U/L in all models and with lower levels in time-varying models. Associations between ALP levels and the composite outcomes were similar. However, compared to serum PTH, mortality predictability of ALP appeared more incremental. CONCLUSIONS: Elevated ALP is associated with increased mortality in patients with pre-dialysis CKD. Low ALP appears to be associated with short-term mortality. PMID- 20299340 TI - Renal denervation reduces glomerular injury by suppressing NAD(P)H oxidase activity in Dahl salt-sensitive rats. AB - BACKGROUND: Renal sympathetic nerve activity has important effects on renal function in chronic kidney disease. Recent studies indicated that beta agonists directly stimulate NAD(P)H oxidase in endothelial cells. Therefore, we investigated whether renal denervation protects renal function through an anti oxidative effect. METHODS: The right kidney was removed from Dahl salt-sensitive hypertensive rats. Two weeks later, the rats underwent either left renal denervation (Nx-RDNx; n = 10) or a sham operation (Nx-Sham; n = 10). After a further 6 weeks, kidney function and renal tissue were assessed. In this ex vivo study, using isolated glomeruli from Sprague-Dawley rats, the direct effects of catecholamine on NAD(P)H oxidase activity were assessed. RESULTS: After the Nx RDNx or Nx-Sham surgery, urinary albumin excretion and the histologic glomerular sclerosis index were lower in the Nx-RDNx group than in the Nx-Sham group. Fluorescence staining for reactive oxygen species in isolated glomeruli was significantly weaker in the Nx-RDNx group. A lucigenin assay of NAD(P)H oxidase activity in isolated glomeruli indicated that renal denervation may have caused the reduction in reactive oxygen species through suppression of the activity of NAD(P)H oxidase. The levels of mRNA for NAD(P)H oxidase components and the levels of rac1 were higher in glomeruli from the Nx-Sham group than from the Nx-RDNx group. In this ex vivo study, although the NAD(P)H oxidase activity did not change with administration of either the alpha- or beta2-agonist, it increased with the beta1-agonist. CONCLUSIONS: Renal sympathetic denervation helps to protect against glomerular sclerosis, possibly by suppressing NAD(P)H oxidase activity, thereby decreasing glomerular reactive oxygen species. PMID- 20299341 TI - Engineering a family of synthetic splicing ribozymes. AB - Controlling RNA splicing opens up possibilities for the synthetic biologist. The Tetrahymena ribozyme is a model group I self-splicing ribozyme that has been shown to be useful in synthetic circuits. To create additional splicing ribozymes that can function in synthetic circuits, we generated synthetic ribozyme variants by rationally mutating the Tetrahymena ribozyme. We present an alignment visualization for the ribozyme termed as structure information diagram that is similar to a sequence logo but with alignment data mapped on to secondary structure information. Using the alignment data and known biochemical information about the Tetrahymena ribozyme, we designed synthetic ribozymes with different primary sequences without altering the secondary structure. One synthetic ribozyme with 110 nt mutated retained 12% splicing efficiency in vivo. The results indicate that our biochemical understanding of the ribozyme is accurate enough to engineer a family of active splicing ribozymes with similar secondary structure but different primary sequences. PMID- 20299342 TI - Sumoylation of Drosophila SU(VAR)3-7 is required for its heterochromatic function. AB - In Drosophila, SU(VAR)3-7 is an essential heterochromatin component. It is required for proper chromatin condensation, and changing its dose modifies position-effect variegation. Sumoylation is a post-translational modification shown to play a role in diverse biological processes. Here, we demonstrate that sumoylation is essential for proper heterochromatin function in Drosophila through modification of SU(VAR)3-7. Indeed, SU(VAR)3-7 is sumoylated at lysine K839; this modification is required for localization of SU(VAR)3-7 at pericentric heterochromatin, chromosome 4, and telomeres. In addition, sumoylation of SU(VAR)3-7 is a prerequisite for its ability to enhance position-effect variegation. Thus, these results show that the heterochromatic function of SU(VAR)3-7 depends on its own sumoylation, and unveil a role for sumoylation in Drosophila heterochromatin. PMID- 20299343 TI - A dictionary on microRNAs and their putative target pathways. AB - While in the last decade mRNA expression profiling was among the most popular research areas, over the past years the study of non-coding RNAs, especially microRNAs (miRNAs), has gained increasing interest. For almost 900 known human miRNAs hundreds of pretended targets are known. However, there is only limited knowledge about putative systemic effects of changes in the expression of miRNAs and their regulatory influence. We determined for each known miRNA the biochemical pathways in the KEGG and TRANSPATH database and the Gene Ontology categories that are enriched with respect to its target genes. We refer to these pathways and categories as target pathways of the corresponding miRNA. Investigating target pathways of miRNAs we found a strong relation to disease related regulatory pathways, including mitogen-activated protein kinase (MAPK) signaling cascade, Transforming growth factor (TGF)-beta signaling pathway or the p53 network. Performing a sophisticated analysis of differentially expressed genes of 13 cancer data sets extracted from gene expression omnibus (GEO) showed that targets of specific miRNAs were significantly deregulated in these sets. The respective miRNA target analysis is also a novel part of our gene set analysis pipeline GeneTrail. Our study represents a comprehensive theoretical analysis of the relationship between miRNAs and their predicted target pathways. Our target pathways analysis provides a 'miRNA-target pathway' dictionary, which enables researchers to identify target pathways of differentially regulated miRNAs. PMID- 20299344 TI - Identification and characterization of the two isoforms of the vertebrate H2A.Z histone variant. AB - Histone variants play important roles in the epigenetic regulation of genome function. The histone variant H2A.Z is evolutionarily conserved from yeast to vertebrates, and it has been reported to have multiple effects upon gene expression and insulation, and chromosome segregation. Recently two genes encoding H2A.Z were identified in the vertebrate genome. However, it is not yet clear whether the proteins transcribed from these genes are functionally distinct. To address this issue, we knocked out each gene individually in chicken DT40 cells. We found that two distinct proteins, H2A.Z-1 and H2A.Z-2, were produced from these genes, and that these proteins could be separated on a long SDS-PAGE gel. The two isoforms were deposited to a similar extent by the SRCAP chromatin-remodeling complex, suggesting redundancy to their function. However, cells lacking either one of the two isoforms exhibited distinct alterations in cell growth and gene expression, suggesting that the two isoforms have differential effects upon nucleosome stability and chromatin structure. These findings provide insight into the molecular basis of the multiple functions of the H2A.Z gene products. PMID- 20299345 TI - Grapevine under deficit irrigation: hints from physiological and molecular data. AB - BACKGROUND: A large proportion of vineyards are located in regions with seasonal drought (e.g. Mediterranean-type climates) where soil and atmospheric water deficits, together with high temperatures, exert large constraints on yield and quality. The increasing demand for vineyard irrigation requires an improvement in the efficiency of water use. Deficit irrigation has emerged as a potential strategy to allow crops to withstand mild water stress with little or no decreases of yield, and potentially a positive impact on fruit quality. Understanding the physiological and molecular bases of grapevine responses to mild to moderate water deficits is fundamental to optimize deficit irrigation management and identify the most suitable varieties to those conditions. SCOPE: How the whole plant acclimatizes to water scarcity and how short- and long distance chemical and hydraulic signals intervene are reviewed. Chemical compounds synthesized in drying roots are shown to act as long-distance signals inducing leaf stomatal closure and/or restricting leaf growth. This explains why some plants endure soil drying without significant changes in shoot water status. The control of plant water potential by stomatal aperture via feed-forward mechanisms is associated with 'isohydric' behaviour in contrast to 'anysohydric' behaviour in which lower plant water potentials are attained. This review discusses differences in this respect between grapevines varieties and experimental conditions. Mild water deficits also exert direct and/or indirect (via the light environment around grape clusters) effects on berry development and composition; a higher content of skin-based constituents (e.g. tannins and anthocyanins) has generally being reported. Regulation under water deficit of genes and proteins of the various metabolic pathways responsible for berry composition and therefore wine quality are reviewed. PMID- 20299346 TI - Nitrogen uptake, assimilation and remobilization in plants: challenges for sustainable and productive agriculture. AB - BACKGROUND: Productive agriculture needs a large amount of expensive nitrogenous fertilizers. Improving nitrogen use efficiency (NUE) of crop plants is thus of key importance. NUE definitions differ depending on whether plants are cultivated to produce biomass or grain yields. However, for most plant species, NUE mainly depends on how plants extract inorganic nitrogen from the soil, assimilate nitrate and ammonium, and recycle organic nitrogen. Efforts have been made to study the genetic basis as well as the biochemical and enzymatic mechanisms involved in nitrogen uptake, assimilation, and remobilization in crops and model plants. The detection of the limiting factors that could be manipulated to increase NUE is the major goal of such research. SCOPE: An overall examination of the physiological, metabolic, and genetic aspects of nitrogen uptake, assimilation and remobilization is presented in this review. The enzymes and regulatory processes manipulated to improve NUE components are presented. Results obtained from natural variation and quantitative trait loci studies are also discussed. CONCLUSIONS: This review presents the complexity of NUE and supports the idea that the integration of the numerous data coming from transcriptome studies, functional genomics, quantitative genetics, ecophysiology and soil science into explanatory models of whole-plant behaviour will be promising. PMID- 20299347 TI - Sonographic visualization and ultrasound-guided blockade of the greater occipital nerve: a comparison of two selective techniques confirmed by anatomical dissection. AB - BACKGROUND: Local anaesthetic blocks of the greater occipital nerve (GON) are frequently performed in different types of headache, but no selective approaches exist. Our cadaver study compares the sonographic visibility of the nerve and the accuracy and specificity of ultrasound-guided injections at two different sites. METHODS: After sonographic measurements in 10 embalmed cadavers, 20 ultrasound guided injections of the GON were performed with 0.1 ml of dye at the classical site (superior nuchal line) followed by 20 at a newly described site more proximal (C2, superficial to the obliquus capitis inferior muscle). The spread of dye and coloration of nerve were evaluated by dissection. RESULTS: The median sonographic diameter of the GON was 4.2 x 1.4 mm at the classical and 4.0 x 1.8 mm at the new site. The nerves were found at a median depth of 8 and 17.5 mm, respectively. In 16 of 20 in the classical approach and 20 of 20 in the new approach, the nerve was successfully coloured with the dye. This corresponds to a block success rate of 80% (95% confidence interval: 58-93%) vs 100% (95% confidence interval: 86-100%), which is statistically significant (McNemar's test, P=0.002). CONCLUSIONS: Our findings confirm that the GON can be visualized using ultrasound both at the level of the superior nuchal line and C2. This newly described approach superficial to the obliquus capitis inferior muscle has a higher success rate and should allow a more precise blockade of the nerve. PMID- 20299348 TI - Effectiveness, safety, and pharmacokinetic and pharmacodynamic characteristics of microemulsion propofol in patients undergoing elective surgery under total intravenous anaesthesia. AB - BACKGROUND: The aims of this study were to investigate the effectiveness, safety, pharmacokinetics, and pharmacodynamics of microemulsion propofol, Aquafol (Daewon Pharmaceutical Co., Ltd, Seoul, Republic of Korea). METHODS: In total, 288 patients were randomized to receive 1% Aquafol or 1% Diprivan (AstraZeneca, London, UK) (n=144, respectively). A 30 mg test dose of propofol was administered i.v. over 2 s for assessing injection pain. Subsequently, a bolus of propofol 2 mg kg(-1) (-30 mg) was administered. Anaesthesia was maintained with a variable rate infusion of propofol and a target-controlled infusion of remifentanil. Mean infusion rates of both formulations and times to loss of consciousness (LOC) and recovery of consciousness (ROC) were recorded. Adverse events and pharmacokinetic and pharmacodynamic characteristics were evaluated. RESULTS: Mean infusion rate of Aquafol was not statistically different from that of Diprivan (median: 6.2 vs 6.3 mg kg(-1) h(-1)). Times to LOC and ROC were slightly prolonged in Aquafol (median: 21 vs 18 s, 12.3 vs 10.8 min). Aquafol showed similar incidence of adverse events to Diprivan. Aquafol (vs Diprivan caused more severe (median VAS: 72.0 vs 11.5 mm) and frequent (81.9 vs 29.2%) injection pain. The dose-normalized AUC(last) of Aquafol and Diprivan was 0.71 (0.19) and 0.74 (0.20) min litre(-1). The V(1) of both formulations were proportional to lean body mass. Sex was a significant covariate for k(12) and Ce(50) of Aquafol, and for k(e0) of Diprivan. CONCLUSIONS: Aquafol was as effective and safe as Diprivan, but caused more severe and frequent injection pain. Aquafol demonstrated similar pharmacokinetics to Diprivan. PMID- 20299349 TI - Percutaneous mitral valve repair with the MitraClip system: acute results from a real world setting. AB - AIMS: This study sought to evaluate the feasibility and early outcomes of a percutaneous edge-to-edge repair approach for mitral valve regurgitation with the MitraClip system (Evalve, Inc., Menlo Park, CA, USA). METHODS AND RESULTS PATIENTS: were selected for the procedure based on the consensus of a multidisciplinary team. The primary efficacy endpoint was acute device success defined as clip placement with reduction of mitral regurgitation to < or =2+. The primary acute safety endpoint was 30-day freedom from major adverse events, defined as the composite of death, myocardial infarction, non-elective cardiac surgery for adverse events, renal failure, transfusion of >2 units of blood, ventilation for >48 h, deep wound infection, septicaemia, and new onset of atrial fibrillation. Thirty-one patients (median age 71, male 81%) were treated between August 2008 and July 2009. Eighteen patients (58%) presented with functional disease and 13 patients (42%) presented with organic degenerative disease. A clip was successfully implanted in 19 patients (61%) and two clips in 12 patients (39%). The median device implantation time was 80 min. At 30 days, there was an intra-procedural cardiac tamponade and a non-cardiac death, resulting in a primary safety endpoint of 93.6% [95% confidence interval (CI) 77.2-98.9]. Acute device success was observed in 96.8% of patients (95% CI 81.5-99.8). Compared with baseline, left ventricular diameters, diastolic left ventricular volume, diastolic annular septal-lateral dimension, and mitral valve area significantly diminished at 30 days. CONCLUSION: Our initial results with the MitraClip device in a very small number of patients indicate that percutaneous edge-to-edge mitral valve repair is feasible and may be accomplished with favourable short-term safety and efficacy results. PMID- 20299350 TI - DNA testing for hypertrophic cardiomyopathy: a cost-effectiveness model. AB - Aims To explore the cost-effectiveness of alternative methods of screening family members for hypertrophic cardiomyopathy (HCM), the most common monogenic cardiac disorder and the most frequent cause of sudden cardiac death (SCD) in young people. Methods and results Economic decision model comparing cascade screening by genetic, as opposed to clinical methods. The incremental cost per life year saved was 14,397 euro for the cascade genetic compared with the cascade clinical approach. Genetic diagnostic strategies are more likely to be cost-effective than clinical tests alone. The costs for cascade molecular genetic testing were slightly higher than clinical testing in the short run, but this was largely because the genetic approach is more effective and identifies more individuals at risk. Conclusion The use of molecular genetic information in the diagnosis and management of HCM is a cost-effective approach to the primary prevention of SCD in these patients. PMID- 20299351 TI - Exercise acutely reverses dysfunction of circulating angiogenic cells in chronic heart failure. AB - AIMS: Recruitment of endothelial progenitor cells (EPCs) and enhanced activity of circulating angiogenic cells (CACs) might explain the benefits of exercise training in reversing endothelial dysfunction in chronic heart failure (CHF) patients. We studied baseline EPC numbers and CAC function and the effect of a single exercise bout. METHODS AND RESULTS: Forty-one CHF patients (mild, n = 22; severe, n = 19) and 13 healthy subjects were included. Migratory activity of CACs was evaluated in vitro and circulating CD34+ and CD34+/KDR+ (EPC) cells were quantified by flow cytometry before and after cardiopulmonary exercise testing (CPET). Circulating stromal cell-derived factor-1alpha (SDF-1alpha) and vascular endothelial growth factor (VEGF) concentrations were measured. Both CAC migration as well as CD34+ cell numbers were significantly reduced in CHF, whereas CD34+/KDR+ cells were not different from controls. Endothelial dysfunction was related to impaired CAC migration (r = 0.318, P = 0.023). Cardiopulmonary exercise testing improved CAC migration in severe (+52%, P < 0.005) and mild CHF (+31%, P < 0.005), restoring it to levels similar to controls. Following CPET, SDF-1alpha increased in healthy controls and mild CHF (P < 0.005). Vascular endothelial growth factor, CD34+, and CD34+/KDR+ cell numbers remained unchanged. CONCLUSION: The present findings reveal a potent stimulus of acute exercise to reverse CAC dysfunction in CHF patients with endothelial dysfunction. PMID- 20299352 TI - Mr Outside and Mr Inside: classic and alternative views on the pathogenesis of rheumatoid arthritis. AB - Different strategies can be applied to overcome an obstacle: one may either overcome it from the 'outside' or break it from the 'inside'. Similar strategies have been successfully used by two American football players in the 1940s, known as 'Mr Outside' and 'Mr Inside'. In this article, the authors propose similar concepts for initiating joint inflammation. Arthritis may start 'outside' as a primary inflammation of the synovial membrane (synovitis), which later spreads over to adjacent structures resulting in penetration into the bone marrow (outside-in concept). Alternatively, arthritis may start 'inside', in the bone marrow space, and later encroaches upon the synovium (inside-out concept). The authors discuss these two fundamentally different viewpoints on the pathogenesis of arthritis, each one of which bears attractive explanations for the mystery of the pathogenesis of arthritis. PMID- 20299353 TI - IL-10/TGF-beta-modified macrophages induce regulatory T cells and protect against adriamycin nephrosis. AB - IL-10/TGF-beta-modified macrophages, a subset of activated macrophages, produce anti-inflammatory cytokines, suggesting that they may protect against inflammation-mediated injury. Here, macrophages modified ex vivo by IL-10/TGF beta (IL-10/TGF-beta Mu2) significantly attenuated renal inflammation, structural injury, and functional decline in murine adriamycin nephrosis (AN). These cells deactivated effector macrophages and inhibited CD4+ T cell proliferation. IL 10/TGF-beta Mu2 expressed high levels of the regulatory co-stimulatory molecule B7-H4, induced regulatory T cells from CD4+CD25- T cells in vitro, and increased the number of regulatory T cells in lymph nodes draining the kidneys in AN. The phenotype of IL-10/TGF-beta Mu2 did not switch to that of effector macrophages in the inflamed kidney, and these cells did not promote fibrosis. Taken together, these data demonstrate that IL-10/TGF-beta-modified macrophages effectively protect against renal injury in AN and may become part of a therapeutic strategy for chronic inflammatory disease. PMID- 20299354 TI - Revisiting basement membrane pathology in renal cystic disease. PMID- 20299356 TI - siRNA therapy for glomerulonephritis. PMID- 20299355 TI - Intercalated cell BK-alpha/beta4 channels modulate sodium and potassium handling during potassium adaptation. AB - The large-conductance, calcium-activated potassium (BK) channels help eliminate potassium in mammals consuming potassium-rich diets. In the distal nephron, principal cells contain BK-alpha/beta1 channels and intercalated cells contain BK alpha/beta4 channels. We studied whether BK-beta4-deficient mice (Kcnmb4(-/-)) have altered renal sodium and potassium clearances compared with wild-type mice when fed a regular or potassium-rich diet for ten days. We did not detect differences in urinary flow or fractional excretions of potassium (FE(K)) or sodium (FE(Na)) between Kcnmb4-deficient and wild-type mice fed a regular diet. However, a potassium-rich diet led to >4-fold increases in urinary flows for both groups of mice, although Kcnmb4-deficient mice exhibited less urinary flow, higher plasma potassium concentration, more fluid retention, and significantly lower FE(K) and FE(Na) than wild-type mice despite similar plasma aldosterone levels. Immunohistochemical analysis revealed increased basolateral Na-K-ATPase in principal cells of all potassium-adapted mice, but expression of Na-K-ATPase in intercalated cells was >10-fold lower. The size of intercalated cells reduced and luminal volume increased among potassium-adapted wild-type but not Kcnmb4 deficient mice. Paradoxically, this led to increased urinary fluid velocity in potassium-adapted Kcnmb4-deficient mice compared with wild-type mice. Taken together, these data suggest that BK-alpha/beta4 channels in intercalated cells reduce cell size, increasing luminal volume to accommodate higher distal flow rates during potassium adaptation. These changes streamline flow across the principal cells, producing gradients more favorable for potassium secretion and less favorable for sodium reabsorption. PMID- 20299357 TI - Idiopathic membranous nephropathy: getting better by itself. PMID- 20299358 TI - Notch2 activation in the embryonic kidney depletes nephron progenitors. AB - Successive activation of Wnt4 and Notch2 generates nephrons from the metanephric mesenchyme. Mesenchymal-to-epithelial transition requires Wnt4, and normal development of the proximal nephron (epithelia of glomeruli and proximal tubules) requires Notch2. It is unknown, however, whether Notch2 dictates the fate of the proximal nephron directly. Here, we generated a mutant strain of mice with activated Notch2 in Six2-containing nephron progenitor cells of the metanephric mesenchyme. Notch2 activation did not skew the cell fate toward the proximal nephron but resulted in severe kidney dysgenesis and depletion of Six2-positive progenitors. We observed ectopic expression of Wnt4 and premature tubule formation, similar to the phenotype of Six2-deficient mice. Activation of Notch2 in the progenitor cells suppressed Pax2, an upstream regulator of Six2, possibly through Hesr genes. Taken together, these data suggest that a positive feedback loop exists between Notch2 and Wnt4, and that Notch2 stabilizes, rather than dictates, nephron fate by shutting down the maintenance of undifferentiated progenitor cells, thereby depleting this population. PMID- 20299359 TI - Reactive oxygen species promote caspase-12 expression and tubular apoptosis in diabetic nephropathy. AB - Apoptosis of tubular epithelial cells contributes to the tubular atrophy that accompanies diabetic nephropathy. Reactive oxygen species (ROS) promote tubular apoptosis, but the mechanisms by which this occurs are incompletely understood. Here, we sought proapoptotic genes that ROS differentially upregulate in renal proximal tubular cells of diabetic (db/db) mice. We performed microarray analysis using total RNA from freshly isolated renal proximal tubules of nondiabetic, diabetic, and diabetic transgenic mice overexpressing catalase in the proximal tubule (thereby attenuating ROS). We observed greater expression of caspase-12 in the proximal tubules of the diabetic mice compared with the nondiabetic and diabetic transgenic mice. Quantitative PCR and immunohistochemistry confirmed the enhanced expression of caspase-12, as well as members of the endoplasmic reticulum stress-induced apoptotic pathway. Ex vivo, albumin induced caspase-12 activity and expression (protein and mRNA) and mRNA expression of the CCAT/enhancer-binding protein homologous protein in freshly isolated wild-type proximal tubules but not in catalase-overexpressing proximal tubules. In vitro, albumin stimulated activity of both caspase-12 and caspase-3 as well as expression of caspase-12 and CCAT/enhancer-binding protein homologous protein in a human proximal tubule cell line (HK-2). The free radical scavenger tiron inhibited these effects. Furthermore, knockdown of caspase-12 with small interfering RNA reduced albumin-induced apoptosis in HK-2 cells. Taken together, these studies demonstrate that albuminuria may induce tubular apoptosis through generation of ROS and the subsequent expression and activation of endoplasmic reticulum stress genes in the diabetic kidney. PMID- 20299361 TI - Th17 cells promote autoimmune anti-myeloperoxidase glomerulonephritis. AB - A major target autoantigen in anti-neutrophil cytoplasmic antibody-associated vasculitis is myeloperoxidase (MPO). Although MPO-specific CD4+ Th cells seem to orchestrate renal injury, the role of the Th17 subset is unknown. We hypothesized that Th17 cells direct injurious anti-MPO autoimmunity in experimental murine anti-MPO-induced glomerulonephritis (GN). We immunized mice with MPO to establish autoimmunity, resulting in systemic IL-17A production with MPO-specific dermal delayed-type hypersensitivity. We triggered disease using antibodies to the glomerular basement membrane to induce glomerular deposition of MPO by neutrophils. Wild-type mice developed necrotizing GN with an influx of glomerular leukocytes and albuminuria. In contrast, mice deficient in the key Th17 effector cytokine IL-17A were nearly completely protected. The protective effects resulted partly from reduced neutrophil recruitment, which led to less disposition of glomerular MPO. To test whether IL-17A also drives autoimmune delayed-type hypersensitivity in the kidney, we injected MPO into the kidneys of MPO sensitized mice. IL-17A deficiency reduced accumulation of renal macrophages and renal CCL5 mRNA expression. In conclusion, IL-17A contributes to the pathophysiology of autoimmune anti-MPO GN, suggesting that it may be a viable therapeutic target for this disease. PMID- 20299360 TI - CCR6 recruits regulatory T cells and Th17 cells to the kidney in glomerulonephritis. AB - T cells recruited to the kidney contribute to tissue damage in crescentic and proliferative glomerulonephritides. Chemokines and their receptors regulate T cell trafficking, but the expression profile and functional importance of chemokine receptors for renal CD4+ T cell subsets are incompletely understood. In this study, we observed that renal FoxP3+CD4+ regulatory T cells (Tregs) and IL 17-producing CD4+ T (Th17) cells express the chemokine receptor CCR6, whereas IFNgamma-producing Th1 cells are CCR6-. Induction of experimental glomerulonephritis (nephrotoxic nephritis) in mice resulted in upregulation of the only CCR6 ligand, CCL20, followed by T cell recruitment, renal tissue injury, albuminuria, and loss of renal function. CCR6 deficiency aggravated renal injury and increased mortality (from uremia) among nephritic mice. Compared with wild type (WT) mice, CCR6 deficiency reduced infiltration of Tregs and Th17 cells but did not affect recruitment of Th1 cells in the setting of glomerulonephritis. Adoptive transfer of WT but not CCR6-deficient Tregs attenuated morphologic and functional renal injury in nephritic mice. Furthermore, reconstitution with WT Tregs protected CCR6-/- mice from aggravated nephritis. Taken together, these data suggest that CCR6 mediates renal recruitment of both Tregs and Th17 cells and that the reduction of anti-inflammatory Tregs in the presence of a fully functional Th1 response aggravates experimental glomerulonephritis. PMID- 20299363 TI - It's time to compare anemia management strategies in hemodialysis. AB - Randomized trials of intravenous (IV) iron have repeatedly demonstrated a rise in hemoglobin (Hgb), an erythropoiesis-stimulating agent (ESA) dose-sparing effect, and apparent safety. Such benefits were confirmed in a trial in hemodialysis patients with high ferritin receiving high ESA doses. But long-term randomized safety trials of IV iron have not been performed, which critics blame on IV iron manufacturers, leading some to question widespread use of IV iron to optimize Hgb and reduce ESA dose. ESAs increase risks of cardiovascular events and death when used to target higher versus lower Hgb values. Association studies report increasing risk with higher ESA doses at approved Hgb targets. Nevertheless, ESAs remain essential in dialysis practice. After early termination of the Normal Hematocrit Trial in 1996, analysis suggested IV iron was a risk factor for harm. In 2006, dangers related to ESA use were recognized. Trial results demonstrating IV iron was efficacious and ESA-sparing even at higher serum ferritin have intensified the focus on iron safety. Two principal alternatives in the management of anemia among dialysis patients are: (1) more intensive ESA dosing sparing iron dosing and (2) more intensive iron dosing sparing ESA dosing. Extended safety trials of IV iron versus no iron will become confounded by ESA dose differences between arms. Similarly higher ESA doses are associated with increased mortality risk, but trials comparing ESA doses will be confounded by Hgb differences. Rather than focus on individual products, we should perform trials comparing anemia management strategies to assess safety, efficacy, and cost. PMID- 20299362 TI - Hypophosphatemic effect of niacin in patients without renal failure: a randomized trial. AB - BACKGROUND AND OBJECTIVES: Niacin administration lowers the marked hyperphosphatemia that is characteristic of renal failure. We examined whether niacin administration also reduces serum phosphorus concentrations in patients who have dyslipidemia and are free of advanced renal disease. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We performed a post hoc data analysis of serum phosphorus concentrations that had been determined serially (at baseline and weeks 4, 8, 12, 18, and 24) among 1547 patients who had dyslipidemia and were randomly assigned in a 3:2:1 ratio to treatment with extended release niacin (ERN; 1 g/d for 4 weeks and dose advanced to 2 g/d for 20 weeks) combined with the selective prostaglandin D2 receptor subtype 1 inhibitor laropiprant (L; n = 761), ERN alone (n = 518), or placebo (n = 268). RESULTS: Repeated measures analysis revealed that ERN-L treatment resulted in a net mean (95% confidence interval) serum phosphorus change comparing ERN-L with placebo treatment of -0.13 mmol/L (-0.15 to -0.13 mmol/L; -0.41 mg/dl [-0.46 to -0.37 mg/dl]). These results were consistent across the subgroups defined by estimated GFR of <60 or > or =60 ml/min per 1.73 m(2), a serum phosphorus of >1.13 mmol/L (3.5 mg/dl) versus < or =1.13 mmol/L (3.5 mg/dl), the presence of clinical diabetes, or concomitant statin use. CONCLUSIONS: We have provided definitive evidence that once-daily ERN L treatment causes a sustained 0.13-mmol/L (0.4-mg/dl) reduction in serum phosphorus concentrations, approximately 10% from baseline, which is unaffected by estimated GFR ranging from 30 to > or =90 ml/min per 1.73 m(2) (i.e., stages 1 through 3 chronic kidney disease). PMID- 20299364 TI - Associations of diet with albuminuria and kidney function decline. AB - BACKGROUND AND OBJECTIVES: Sparse longitudinal data exist on how diet influences microalbuminuria and estimated GFR (eGFR) decline in people with well-preserved kidney function. DESIGN, SETTINGS, PARTICIPANTS, & MEASUREMENTS: Of the 3348 women participating in the Nurses' Health Study who had data on urinary albumin to creatinine ratio in 2000, 3296 also had data on eGFR change between 1989 and 2000. Cumulative average intake of nutrients over 14 years was derived from semiquantitative food frequency questionnaires answered in 1984, 1986, 1990, 1994, and 1998. Microalbuminuria presence and eGFR decline > or = 30% were the outcomes of interest. RESULTS: Compared with the lowest quartile, the highest quartile of animal fat (odds ratio (OR): 1.72; 95% confidence interval (CI): 1.12 to 2.64) and two or more servings of red meat per week (OR: 1.51; 95% CI: 1.01 to 2.26) were directly associated with microalbuminuria. After adjustment for other nutrients individually associated with eGFR decline > or = 30%, only the highest quartile of sodium intake remained directly associated (OR: 1.52; 95% CI: 1.10 to 2.09), whereas beta-carotene appeared protective (OR: 0.62, 95% CI: 0.43 to 0.89). Results did not vary by diabetes status for microalbuminuria and eGFR outcomes or in those without hypertension at baseline for eGFR decline. No significant associations were seen for other types of protein, fat, vitamins, folate, fructose, or potassium. CONCLUSIONS: Higher dietary intake of animal fat and two or more servings per week of red meat may increase risk for microalbuminuria. Lower sodium and higher beta-carotene intake may reduce risk for eGFR decline. PMID- 20299365 TI - Performance of the Cockcroft-Gault, MDRD, and new CKD-EPI formulas in relation to GFR, age, and body size. AB - BACKGROUND AND OBJECTIVES: We compared the estimations of Cockcroft-Gault, Modification of Diet in Renal Disease (MDRD), and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations to a gold standard GFR measurement using (125)I-iothalamate, within strata of GFR, gender, age, body weight, and body mass index (BMI). DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: For people who previously underwent a GFR measurement, bias, precision, and accuracies between measured and estimated kidney functions were calculated within strata of the variables. The relation between the absolute bias and the variables was tested with linear regression analysis. RESULTS: Overall (n = 271, 44% male, mean measured GFR 72.6 ml/min per 1.73 m(2) [SD 30.4 ml/min per 1.73 m(2)]), mean bias was smallest for MDRD (P < 0.01). CKD-EPI had highest accuracy (P < 0.01 compared with Cockcroft-Gault), which did not differ from MDRD (P = 0.14). The absolute bias of all formulas was related to age. For MDRD and CKD-EPI, absolute bias was also related to the GFR; for Cockcroft-Gault, it was related to body weight and BMI as well. In all extreme subgroups, MDRD and CKD-EPI provided highest accuracies. CONCLUSIONS: The absolute bias of all formulas is influenced by age; CKD-EPI and MDRD are also influenced by GFR. Cockcroft-Gault is additionally influenced by body weight and BMI. In general, CKD-EPI gives the best estimation of GFR, although its accuracy is close to that of the MDRD. PMID- 20299366 TI - Transfusion burden among patients with chronic kidney disease and anemia. AB - BACKGROUND AND OBJECTIVES: Although well-described for patients who require dialysis, information on transfusion burden related to anemia in the nondialysis patient population with chronic kidney disease (CKD) is lacking. DESIGN, SETTINGS, PARTICIPANTS, & MEASUREMENTS: A retrospective study was conducted of patients with CKD and chronic anemia from 2002 through 2007 in the Veterans Administration Healthcare System. Included patients had stage 3 CKD or higher and anemia (one or more hemoglobin [Hb] levels <11 g/dl or received anemia therapy [erythropoiesis-stimulating agents [ESAs], iron, or both]). The outcome of interest was transfusion events, which was evaluated in relation to the absolute Hb level and changes in Hb levels overall and according to the type of treatment received (no treatment, iron therapy, ESA therapy, or ESA and iron therapy) concurrent with each Hb measurement. RESULTS: Among 97,636 patients with CKD and anemia, we observed 68,556 transfusion events (61 events per 100 person-years), 86.6% of which occurred in inpatient settings. At all Hb levels, transfusion events were highest during periods of no treatment and increased with declining Hb levels. Between an Hb of 10.0 and 10.9 g/dl, the transfusion rate was 2.0% for those who received an ESA, iron, or both and 22% for those who received no treatment; at an Hb level of 7.0 to 7.9 g/dl, the transfusion rate was 10 to 12% for treated and 58% for untreated patients. Low absolute Hb levels but not Hb changes was most predictive of a transfusion even after adjustment for patient case mix. CONCLUSIONS: Transfusions are still used to treat anemia in patients who have CKD and do not require dialysis, although they occur considerably less frequently in patients who receive other available anemia therapies. PMID- 20299367 TI - Glomerular hyperfiltration in sickle cell disease. PMID- 20299368 TI - Examination of association with candidate genes for diabetic nephropathy in a Mexican American population. AB - BACKGROUND AND OBJECTIVES: Diabetic nephropathy (DN) is a multifactorial complication characterized by persistent proteinuria in susceptible individuals with type 1 and type 2 diabetes. Disease burden in people of Mexican-American descent is particularly high, but there are only a few studies that characterize genes for DN in this ethnic group. Two genes, carnosine dipeptidase 1 (CNDP1) and engulfment and cell motility 1 (ELMO1) previously showed association with DN in other ethnic groups. CNDP1 and ELMO1 were examined along with eight other genes that are less well characterized for DN in a new study of Mexican-Americans. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: The target sample was patients of Mexican-American ancestry collected from three centers: 455 patients with DN and 437 controls with long-term diabetes but no incident nephropathy. Forty-two, 227, and 401 single nucleotide polymorphisms (SNPs) in CNDP1, ELMO1, and the other eight genes, respectively, were examined. RESULTS: No region in CNDP1 or ELMO1 showed significant P values. Of the other eight candidate genes, an association of DN with a SNP pair, rs2146098 and rs6659783, was found in hemicentin 1 (HMCN1) (unadjusted P = 6.1 x 10(-5)). Association with a rare haplotype in this region was subsequently identified. CONCLUSIONS: The associations in CNDP1 or ELMO1 were not replicable; however, an association of DN with HMCN1 was found. Additional work at this and other loci will enable refinement of the genetic hypotheses regarding DN in the Mexican-American population to find therapies for this debilitating disease. PMID- 20299369 TI - Nephrogenic systemic fibrosis: a survey of nephrologists' perceptions and practices. AB - BACKGROUND AND OBJECTIVES: Nephrogenic systemic fibrosis (NSF) is a disorder that can affect patients with renal dysfunction exposed to a gadolinium-based contrast agent (GBCA). Given the unique role nephrologists play in caring for patients at risk to develop NSF, this study surveyed their perceptions and practices regarding NSF. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: An internet-based, cross-sectional survey of clinical nephrologists in the United States was performed. Perceptions and self-reported practices regarding NSF and local facility policies were assessed concerning GBCA use in renal dysfunction. RESULTS: Of the 2310 eligible nephrologists e-mailed to participate in the survey, 171 (7.4%) responded. Respondents spent 85% of their time in direct patient care and 83% worked in private practice; 59% had cared for a patient with NSF. Although over 90% were aware of the morbidity and mortality associated with NSF, 31% were unaware of an association with specific GBCA brand and 50% believed chronic kidney disease stage 3 patients were at risk to develop NSF. Changes in facility policies concerning GBCA use in renal dysfunction were widespread (>90%). Most nephrologists (56%) felt that enacted policies were appropriate, yet 58% were uncertain if the changes had benefited patients. CONCLUSIONS: These results indicate that nephrologists are generally familiar with the risk factors and consequences of NSF, but their perceptions do not always align with current evidence. Local policy changes in GBCA use are pervasive. Most nephrologists are comfortable with these policy changes but have mixed feelings regarding their effectiveness. PMID- 20299370 TI - Renal angina. AB - Small elevations in serum creatinine may reflect significant kidney damage and be associated with poor patient outcomes, thus rendering creatinine to be a late marker of acute kidney injury (AKI). AKI researchers refer to the AKI biomarker quest as the "search for the renal troponin I," implying that such putative earlier AKI biomarker use could allow for earlier intervention. We consider the analogy to troponin I and its acceptance to prompt evaluation and therapeutic intervention to treat myocardial ischemia and prevent myocardial infarction an informative and potentially applicable model to the AKI field. Because AKI does not hurt, there is no validated equivalent of chest pain or anginal equivalent to increase suspicion for AKI presence on the part of the clinician. So, although biomarkers may ultimately be validated to detect AKI early, unless nephrologists and intensivists can define "renal angina" to initiate "renal troponin I" assessments, AKI biomarkers may never realize their full potential to improve patient care and outcomes. The purpose of this article is to review both adult and pediatric AKI literature to devise a definition for a renal anginal syndrome equivalent. PMID- 20299371 TI - Attitudes to sharing personal health information in living kidney donation. AB - BACKGROUND AND OBJECTIVES: In living kidney donation, transplant professionals consider the rights of a living kidney donor and recipient to keep their personal health information confidential and the need to disclose this information to the other for informed consent. In incompatible kidney exchange, personal health information from multiple living donors and recipients may affect decision making and outcomes. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We conducted a survey to understand and compare the preferences of potential donors (n = 43), potential recipients (n = 73), and health professionals (n = 41) toward sharing personal health information (in total 157 individuals). RESULTS: When considering traditional live-donor transplantation, donors and recipients generally agreed that a recipient's health information should be shared with the donor (86 and 80%, respectively) and that a donor's information should be shared with the recipient (97 and 89%, respectively). When considering incompatible kidney exchange, donors and recipients generally agreed that a recipient's information should be shared with all donors and recipients involved in the transplant (85 and 85%, respectively) and that a donor's information should also be shared with all involved (95 and 90%, respectively). These results were contrary to attitudes expressed by transplant professionals, who frequently disagreed about whether such information should be shared. CONCLUSIONS: Future policies and practice could facilitate greater sharing of personal health information in living kidney donation. This requires a consideration of which information is relevant, how to put it in context, and a plan to obtain consent from all concerned. PMID- 20299372 TI - Prevalence of ocular fundus pathology in patients with chronic kidney disease. AB - BACKGROUND AND OBJECTIVES: The objective of this study was to describe the prevalence of ocular fundus pathology in the Chronic Renal Insufficiency Cohort (CRIC) study, a multicenter, longitudinal study of individuals with varying stages of chronic kidney disease (CKD). DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: In this cross-sectional study, 45 degree digital photos of the disc and macula in both eyes were obtained by nonophthalmologic personnel using a nonmydriatic Canon CR-DGI fundus camera in 1936 individuals who participated in the CRIC study. Photographs were assessed in a masked manner by graders and a retinal specialist at a central photograph reading center. The purpose of this review was to inform participants quickly of conditions that warranted a complete eye examination by an ophthalmologist. RESULTS: Among the 1936 participants who were photographed, 1904 (98%) had assessable photographs in at least one eye. Eye pathologies that required a follow-up examination by an ophthalmologist were identified in 864 (45%) of these 1904 participants. These eye pathologies included, among others, retinopathy (diabetic and/or hypertensive), a finding that was observed in 482 (25%) of these 1904 participants. Three percent (65 participants) of the 1904 participants had serious eye conditions that required urgent follow-up and treatment. Lower estimated GFR and cardiovascular disease were associated with greater eye pathology. Estimated GFR <30 ml/min per 1.73 m(2) was associated with a three times higher risk for retinopathy. CONCLUSIONS: We found a high prevalence of fundus pathology in participants with CKD. This finding supports recommendations for regular complete eye examinations in the CKD population. PMID- 20299373 TI - Dose of dialysis based on body surface area is markedly less in younger children than in older adolescents. AB - BACKGROUND AND OBSERVATIONS: The current denominator for dosing dialysis is the urea distribution volume (V). Normalizing Kt/V to body surface area (S) has been proposed, but the implications of doing this in children have not been examined. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Dialysis dose given to children and adolescents was calculated in terms of conventional V-based scaling and surface-area-normalized standard Kt/V (SAN-stdKt/V) calculated as stdKt/V x (Vant/S)/17.5, where Vant was an anthropometric estimate of V calculated using the Morgenstern equation. Formal 2-pool modeling was used to compute all dialysis adequacy outputs. RESULTS: In 34 children (11 girls, 23 boys) dialyzed 3 times a week, age range 1.4 to 18 years, the mean delivered equilibrated Kt/V (eKt/V) was 1.40, and the mean stdKt/V was 2.49, both of which tended to be higher in younger children. The ratio of Vant to S was 15.6 +/- 2.69 and was strongly associated with age between ages 2 and 16. SAN-stdKt/V averaged 2.21 and was strongly correlated with age between ages 2 and 16. If one considers a desired target for SAN-stdKt/V to be 2.45, all children less than 10 years of age were below target, despite having relatively high values of eKt/V and stdKt/V. CONCLUSIONS: If a surface-area-based denominator were to be adopted for dialysis dosing, most children under 10 years of age would receive markedly less dialysis than adolescent patients and would require 6- to 8-hour hemodialysis sessions or, for the youngest children, treatments given more frequently than 3 times/wk. PMID- 20299374 TI - The spectrum of MYH9-associated nephropathy. AB - Causes of the excess incidence rates of chronic kidney disease in the African American population have long been under study. Recently, polymorphisms in the nonmuscle myosin heavy chain 9 gene (MYH9) have been associated with nondiabetic kidney diseases in African- and European-derived populations. Risk variants in MYH9 contribute to approximately 70% of nondiabetic forms of ESRD in African Americans and 40 to 45% of all ESRD in this ethnic group, with lesser effects in European Americans. It is clear that MYH9 polymorphisms have a significant impact on the incidence rates of kidney disease in African Americans. This article describes the current spectrum of biopsy-proven MYH9-associated kidney diseases, along with potential effects of MYH9 on ethnic differences in clinical outcome. MYH9 risk variants exhibit the most impressive association with any common complex kidney disease yet identified. PMID- 20299375 TI - Reduction of serum hepcidin by hemodialysis in pediatric and adult patients. AB - BACKGROUND AND OBJECTIVES: Hepcidin, the principal regulator of iron homeostasis, may play a critical role in the response of patients with anemia to iron and erythropoiesis-stimulating agent therapy; however, the contribution of hepcidin to iron maldistribution and anemia in hemodialysis (HD) patients and the ability of HD to lower serum hepcidin levels have not been fully characterized. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We measured serum hepcidin using a competitive ELISA in 30 pediatric and 33 adult HD patients. In addition, we determined serum hepcidin kinetics and calculated hepcidin clearance by measuring serum hepcidin before, during, and after HD in eight pediatric and six adult patients. RESULTS: Hepcidin was significantly increased in pediatric (median 240.5 ng/ml) and adult HD patients (690.2 ng/ml) when compared with their respective control subjects (pediatric 25.3 ng/ml, adult 72.9 ng/ml). Multivariate regression analysis showed that serum hepcidin was independently predicted by ferritin and high-sensitivity C-reactive protein in the pediatric group and ferritin, percentage of iron saturation, and high-sensitivity C reactive protein in the adult group. Hepcidin levels decreased after dialysis from 532 +/- 297 to 292 +/- 171 ng/ml. Hepcidin clearance by HD was 141 +/- 40 and 128 +/- 44 ml/min in pediatric and adult patients, respectively (NS). CONCLUSIONS: These findings suggest that hepcidin may mediate the negative effects of inflammation on both disordered iron metabolism and erythropoiesis in HD patients and that intensification of HD could be used therapeutically to reduce hepcidin concentrations and thereby improve erythropoiesis-stimulating agent responsiveness. PMID- 20299376 TI - Sickle cell trait and development of microvascular complications in diabetes mellitus. AB - BACKGROUND AND OBJECTIVES: Many African Americans (AA) have both sickle cell trait (SCT) and diabetes mellitus. The objective of this study was to determine whether individuals with diabetes mellitus and SCT have higher rates of microvascular complications relative to those without SCT. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This was a retrospective study comparing albuminuria, estimated GFR (eGFR), and microvascular complications in AA with diabetes on the basis of presence of SCT. The study included 821 outpatients who underwent hemoglobin A1c (HbA1c) testing, and presence of SCT was determined using the HbA1c assay. Medical record review and telephone interviews were performed for AA participants. RESULTS: Data were obtained on 376 AA patients (110 with SCT, 245 with neither SCT nor hemoglobin C trait, and 21 with hemoglobin C trait) and 445 European Americans. The mean eGFR and urinary protein excretion were similar between the three AA subgroups. Analysis revealed that 36.3% of AA nontrait and 22.7% of AA SCT participants had retinopathy, peripheral vascular disease, or end-stage kidney disease (P = 0.01). After adjustment for diabetes duration, age, insulin use, and gender, differences in the prevalence of microvascular complications were not observed. CONCLUSIONS: SCT does not increase the risk of microvascular complications in AA with diabetes mellitus. PMID- 20299378 TI - Cancer risk in patients hospitalized with polymyalgia rheumatica and giant cell arteritis: a follow-up study in Sweden. AB - OBJECTIVES: Studies reporting cancer risk after PMR and GCA are few, but it remains an issue of both concern and controversy. We examined the overall and specific cancer risks among Swedish subjects following hospitalization for these diseases. METHODS: PMR and GCA patients were identified from the Swedish Hospital Discharge Register and by linking them with the Cancer Registry. Follow-up of patients was carried out from the last hospitalization through year 2006. Standardized incidence ratios (SIRs) were calculated in these patients compared with subjects without the diseases. RESULTS: A total of 35 918 patients were hospitalized for PMR and GCA during the years 1965-2006; the hospitalization rate increased towards late age. A total of 3941 patients developed subsequent cancer, giving an overall SIR of 1.19; and for cancer diagnosed later than 1 year of follow-up, the SIR was 1.06. A significant excess was noted for skin (squamous cell carcinoma and melanoma), stomach, lung, prostate, kidney, nervous system and endocrine gland tumours, and additionally for non-Hodgkin's lymphoma, myeloma and leukaemia. Decreased risk was noted for endometrial cancer. CONCLUSIONS: Patients hospitalized for PMR and GCA had a marginally increased risk of cancer, with the highest risk noted for the first year after hospitalization. However, for specific cancers, such as skin cancer and leukaemia, the increases were still significant for patients diagnosed later than 1 year after hospitalization, suggesting that these could be true associations, but the mechanisms remain to be established. PMID- 20299377 TI - Timing of erythropoiesis-stimulating agent initiation and adverse outcomes in nondialysis CKD: a propensity-matched observational study. AB - BACKGROUND AND OBJECTIVES: The severity of anemia at which to initiate erythropoiesis-stimulating agent (ESA) treatment in nondialysis chronic kidney disease (CKD) patients is unclear. Risk of mortality, hospitalizations, and blood transfusion were compared among nondialysis CKD patients with "early" versus "delayed" ESA initiation. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: A retrospective cohort study was conducted on CKD (estimated GFR <60 ml/min/1.73m(2)) outpatients in the national Veterans Administration who were initiated on ESAs. Patients with ESRD, gastrointestinal bleeding, chemotherapy, or hematologic malignancy were excluded. Patients were characterized as having early [hemoglobin (Hb) 10.0 to 11.0 g/dl] or delayed (Hb 8.0 to 9.9 g/dl) ESA initiation. A propensity score comprising demographic, clinical, and laboratory variables was used to select a 1:1 matched cohort. Cox survival and negative binomial regression were used to compare the matched groups for all-cause mortality, hospitalizations, and blood transfusions. RESULTS: Of 1837 patients who met inclusion criteria, 1410 (77%) were successfully matched. The groups did not differ significantly in 31 characteristics reflecting sociodemographics, comorbidity, healthcare utilization, and renal function. There was no significant difference in mortality with early initiation. Those initiated early had a 17% lower risk of initial hospitalization and a 29% lower risk of transfusion compared with delayed initiation patients. Results did not differ between those with and without pre-ESA transfusion or hospitalization. CONCLUSIONS: In nondialysis CKD, ESA initiation at Hb 10.0 to 11.0 g/dl compared with 8.0 to 9.9 g/dl is associated with reduced risk of blood transfusion and initial hospitalization. PMID- 20299379 TI - Common and recurrent HPGD mutations in Caucasian individuals with primary hypertrophic osteoarthropathy. AB - OBJECTIVE: Homozygous recessive germline mutations of the 15-hydroxyprostaglandin dehydrogenase (HPGD) gene, encoding 15-hydroxyprostaglandin dehydrogenase, result in persistent elevation of circulating PGE(2) levels, causing the syndrome of primary hypertrophic osteoarthropathy (PHO). Homozygous HPGD mutations have so far been reported in 10 families, all but one displaying parental consanguinity. Only two of these families were of European origin. We wished to determine the role of HPGD in causing PHO in non-consanguineous European families. METHODS: Five previously unreported families of Caucasian European origin, with one or more individuals affected with typical PHO, were characterized clinically and by complete sequencing of the HPGD coding exons. RESULTS: Biallelic HPGD mutations were identified in affected individuals in all the five families, confirming a very specific association of this phenotype with HPGD mutations. The previously described c.175_176delCT frameshift mutation was observed in association with two different alleles of an adjacent single nucleotide polymorphism. CONCLUSIONS: Biallelic HPGD mutations are found in the majority of patients with typical PHO, and sequencing of the HPGD gene is a highly specific first-line investigation for patients presenting in this way, particularly during childhood. The c.175_176delCT frameshift mutation appears to be recurrent and to be the commonest HPGD mutation in Caucasian families. PMID- 20299380 TI - Articular manifestations in primary Sjogren's syndrome: clinical significance and prognosis of 188 patients. AB - OBJECTIVES: Articular manifestations (AMs) occurred in approximately 30-60% of patients with primary SS (pSS). We conducted the current study to describe clinical presentation, specific treatment and to report clinical outcome of pSS patients with AM in a large bicentric French cohort. METHODS: Clinical, biological and immunological features of 419 consecutive patients with pSS were recorded in order to describe the clinical and immunological course of pSS AM and to point out the impact of those rheumatological features on pSS evolution. RESULTS: A total of 188 patients with pSS (172 women, 16 men) exhibited AM. They preceded sicca symptoms in 32, were simultaneous to pSS diagnosis in 98 and followed diagnosis in 59 patients. Clinical presentation was polyarticular and concerned mostly peripheral joints (synovitis, n = 66). Symptoms responded readily to symptomatic treatment in 45 cases (24%). DMARDs or immunosuppressive treatments were introduced in 133 patients: HCQ (n = 111), corticosteroid (n = 53), MTX (n = 12), SSZ (n = 6), AZA (n = 3), LEF (n = 1), etanercept (n = 1) and allochrysine (n = 1). Only one case of RA was diagnosed during the evolution. Statistical analysis identified clinical and biological factors associated with AM (P < or = 0.05): RP, muscular manifestations, renal involvement, peripheral neuropathy, cutaneous vasculitis, and positivity of RF, anti-SSB antibodies and cryoglobulinaemia. Patients with AM at diagnosis were characterized by a multisystemic involvement at the end of the follow-up period (P < 0.001). CONCLUSION: Although AMs are frequent and usually mild in pSS, these manifestations are associated with a pluri-systemic involvement of pSS. PMID- 20299381 TI - Dysregulation of P2X7 receptor-inflammasome axis in SAPHO syndrome: successful treatment with anakinra. PMID- 20299382 TI - The tumour necrosis factor-related apoptosis-inducing ligand-osteoprotegerin system in limited systemic sclerosis: a new disease marker? AB - OBJECTIVE: To investigate the role of the TNF-related apoptosis-inducing ligand osteoprotegerin (TRAIL-OPG) system in the pathogenesis of limited SSc (lSSc). METHODS: Circulating levels of TRAIL and of its soluble receptor OPG were measured by ELISA in serum samples obtained from 50 lSSc patients and 50 healthy controls. RESULTS: TRAIL serum levels in lSSc patients were similar to those of healthy controls, whereas the OPG serum levels were significantly increased (P < 0.0001). According to different subgroups of lSSc patients, TRAIL was not statistically different between each group and healthy controls; concerning OPG, the statistically different value was also maintained when comparing each single lSSc group with the whole control population. CONCLUSIONS: OPG serum levels, but not TRAIL, are elevated in lSSc patients. Since OPG binding to TRAIL inhibits TRAIL-TRAIL receptor interaction, the relative concentrations of these two molecules in the local micro-environment has to be considered. In this setting, OPG increase in lSSc patients may produce a detrimental effect by counteracting the vasoprotective activity of TRAIL. The TRAIL : OPG ratio and their relative levels of expression in lSSc patients should be taken into consideration as a possible novel marker of vascular damage. PMID- 20299383 TI - Mothers of IVF and spontaneously conceived twins: a comparison of prenatal maternal expectations, coping resources and maternal stress. AB - BACKGROUND: This study explores the differences in prenatal maternal expectations, coping resources and maternal stress between first time mothers of IVF twins and first time mothers of spontaneously conceived twins. The role of prenatal maternal expectations in the prediction of maternal stress was examined, as well as the mediating and moderating effect of coping resources on the association between pregnancy-type group and maternal stress. METHOD: Mothers of twins from various regions in Israel were included in this prospective and cross sectional study in which 88 mothers of IVF-conceived twins and 98 mothers of spontaneously conceived twins were interviewed twice. First, at 33-36 weeks of their pregnancy they completed a socio-demographic questionnaire and the maternal expectations questionnaire; then at 6 months after birth they completed a questionnaire regarding the delivery and medical condition of the infants, and their coping resources and maternal stress. RESULTS: Compared with mothers who conceived spontaneously, IVF mothers had more positive prenatal maternal expectations, but poorer coping resources and higher levels of maternal stress 6 months after birth. Maternal expectations had no predictive power regarding maternal stress, although the mother's coping resources were significantly related to maternal stress and mediated the association between pregnancy type and maternal stress. CONCLUSIONS: IVF-pregnant women bearing twins should be considered a high-risk group. Early identification of these mothers is essential for timely psychosocial interventions in order to enhance their resources and decrease maternal stress. Further longitudinal studies are required to determine causality in more ethnically-diverse mothers of twins. PMID- 20299384 TI - Xenotransplantation of cryopreserved human ovarian tissue into murine back muscle. AB - BACKGROUND: Ovarian tissue (OT) cryopreservation and transplantation are options for fertility preservation in young female cancer patients. METHODS: We investigated xenotransplantation of human OT into back muscle (B) of severe combined immunodeficiency mice. OT follicle content was evaluated by stereomicroscopy and pre-transplantation. Xenograft survival, follicular development (with/without FSH administration), apoptosis and vascularization were compared in B- versus K-site (under the kidney capsule) several times after grafting using histology, immunohistochemistry and magnetic resonance imaging. In vitro maturation (IVM) was also performed. RESULTS: Anastomoses which developed from existing human and invading murine vessels were seen in OT at both sites, but angiogenesis was more prominent at the B- than K-site (P < 0.001). Vascularization and follicle size were correlated in the B-group (Spearman's coefficient 0.73; P < 0.001). FSH increased early (8 days) micro-vessel formation in B but not in K grafts (P < 0.0001, versus no FSH). B-site grafts showed a better histological morphology and survival (P = 0.0084), formation of larger antral follicles (P = 0.005), more metaphase-II (MII) oocytes, growing follicles (P = 0.028) and slightly fewer apoptotic follicles than K grafts. One MI oocyte from B underwent IVM and reached MII stage next day. CONCLUSIONS: To our knowledge, this is the first report of MII and IVM-MII oocytes obtained from B xenografts. We report the largest oval-shaped antral follicles containing an MII oocyte obtained after OT xenotransplantation to date. Xenografting in the mouse B should be further explored as a method for human OT transplantation. PMID- 20299385 TI - Private-payer profits can induce negative Medicare margins. AB - A common assumption is that hospitals have little control over their costs and must charge high rates to private health insurers when Medicare rates are lower than hospital costs. We present evidence that contradicts that common assumption. Hospitals with strong market power and higher private-payer and other revenues appear to have less pressure to constrain their costs. Thus, these hospitals have higher costs per unit of service, which can lead to losses on Medicare patients. Hospitals under more financial pressure--with less market share and less ability to charge higher private rates--often constrain costs and can generate profits on Medicare patients. PMID- 20299386 TI - A Six Sigma approach to the rate and clinical effect of registration errors in a laboratory. AB - BACKGROUND: Laboratory errors made during the pre-analytical phase can have an impact on clinical care. Quality management tools such as Six Sigma may help improve error rates. AIM: To use elements of a Six Sigma model to establish the error rate of test registration onto the laboratory information system (LIS), and to deduce the potential clinical impact of these errors. METHODS: In this retrospective study, test request forms were compared with the tests registered onto the LIS, and all errors were noted before being rectified. The error rate was calculated. The corresponding patient records were then examined to determine the actual outcome, and to deduce the potential clinical impact of the registration errors. RESULTS: Of the 47 543 tests requested, 72 errors were noted, resulting in an error rate of 0.151%, equating to a sigma score of 4.46. The patient records reviewed indicated that these errors could, in various ways, have impacted on clinical care. CONCLUSION: This study highlights the clinical effect of errors made during the pre-analytical phase of the laboratory testing process. Reduction of errors may be achieved through implementation of a Six Sigma programme. PMID- 20299387 TI - The role of endobronchial ultrasound guided transbronchial needle aspiration cytology in the investigation of mediastinal lymphadenopathy and masses, the North Tees experience. AB - AIM: To assess the diagnostic role of endobronchial ultrasound (EBUS) guided transbronchial fine needle aspiration (TBNA) cytology, in the investigation of mediastinal lymphadenopathy and masses, with emphasis on pathology, criteria for adequacy, and use of liquid based cytology (LBC). METHODS: In January 2008, EBUS guided TBNA was introduced for the staging of lung cancers and for the investigation of unexplained mediastinal lymphadenopathy and masses. Initially, the material was processed conventionally. In May 2008, the laboratory procured the Cytyc T2000. RESULTS: 250 specimens (229 patients) were included from January 2008 to August 2009. The overall inadequate rate was 12%; 16.6% with the conventional method, 17.2% when both conventional and LBC were used, and 9.8% with LBC. With the conventional method, an average of 7.5 slides and one cell block were received per case. With LBC, one slide and one cell block were used for diagnosis. In 72 cases (28.8%) the aspirate showed no evidence of malignancy. In 122 cases (48.8%), there was metastatic disease. In five cases (2%), a diagnosis of atypia, suspicious for non-small cell malignancy, was made. One case (0.4%) each of amyloidosis and mediastinal goitre, 3 cases (1.2%) of lymphoma, 14 cases (5.6%) of sarcoidosis and 1 case (0.4%) each of sarcoma and mesothelioma were seen. CONCLUSIONS: EBUS guided TBNA, in our experience, is a reliable technique for staging of lung cancers, and investigation of unexplained mediastinal lymphadenopathy and masses. LBC reduces the number of slides from 7.5 per case to 1 slide, reducing time required for diagnosis. PMID- 20299388 TI - Multifocal polypoid endometriosis in a young woman simulating vaginal and pelvic neoplasm. AB - A 27-year-old nulliparous woman presented with large finger-like projections protruding from her vagina. Intraoperatively there were deposits in the pouch of Douglas. Clinical presentation and history of vaginal bleeding suggested malignancy. Histopathology of both the vaginal and pouch of Douglas masses showed endometrial glands and stroma. There was no architectural complexity or cytological atypia of glands or stroma. Immunohistochemistry for oestrogen receptor, progesterone receptor and CD10 was positive. Based on morphological and immunohistochemical findings, multifocal polypoid endometriosis was diagnosed; this is a recently described entity having a clinical presentation and age range completely different from conventional or non-polypoid endometriosis. Although an association between tamoxifen use, unopposed oestrogen therapy and polypoid endometriosis has been suggested, the patient had no history of tamoxifen or oestrogen intake. Polypoid endometriosis should be part of the differential diagnosis in young women presenting with vaginal growth. PMID- 20299389 TI - Early functional magnetic resonance imaging activations predict language outcome after stroke. AB - An accurate prediction of system-specific recovery after stroke is essential to provide rehabilitation therapy based on the individual needs. We explored the usefulness of functional magnetic resonance imaging scans from an auditory language comprehension experiment to predict individual language recovery in 21 aphasic stroke patients. Subjects with an at least moderate language impairment received extensive language testing 2 weeks and 6 months after left-hemispheric stroke. A multivariate machine learning technique was used to predict language outcome 6 months after stroke. In addition, we aimed to predict the degree of language improvement over 6 months. 76% of patients were correctly separated into those with good and bad language performance 6 months after stroke when based on functional magnetic resonance imaging data from language relevant areas. Accuracy further improved (86% correct assignments) when age and language score were entered alongside functional magnetic resonance imaging data into the fully automatic classifier. A similar accuracy was reached when predicting the degree of language improvement based on imaging, age and language performance. No prediction better than chance level was achieved when exploring the usefulness of diffusion weighted imaging as well as functional magnetic resonance imaging acquired two days after stroke. This study demonstrates the high potential of current machine learning techniques to predict system-specific clinical outcome even for a disease as heterogeneous as stroke. Best prediction of language recovery is achieved when the brain activation potential after system-specific stimulation is assessed in the second week post stroke. More intensive early rehabilitation could be provided for those with a predicted poor recovery and the extension to other systems, for example, motor and attention seems feasible. PMID- 20299390 TI - Profiling of heparin-induced thrombocytopenia antibody levels in patients with and without diabetes. AB - Heparin/platelet factor 4 (H:PF4) antibodies are the causative agent in heparin induced thrombocytopenia (HIT). The antibodies are frequently formed after exposure to heparin, most commonly without any signs of clinical HIT. Heparin induced thrombocytopenia antibodies have been detected by enzyme-linked immunosorbent assay (ELISA) in individuals who have not been exposed to heparin. It is possible that the antibodies could be elicited by PF4 associated with endogenous, heparin-like glycosaminoglycans (GAGs). This risk would be higher in individuals with endothelial dysfunction and chronic platelet activation. In the setting of an outpatient endocrinology clinic, both diabetic and nondiabetic patients were studied and compared with healthy volunteers. Heparin/platelet factor 4 antibody titers were measured by ELISA and analyzed to determine the frequency of clinically seropositive responses, and median and interquartile ranges of baseline antibody titers. The study found no increase in frequency of ELISA-positive patients among diabetic patients. Moreover, the diabetic population had lower overall level of H:PF4 antibody titer, especially the subgroups treated with thiazolidinedione drugs or angiotensin receptor blockers. Further studies are needed to determine whether subthreshold titers of HIT antibody may be reflective of the physiological state of platelet/endothelial balance. PMID- 20299391 TI - Antiplatelet therapy prasugrel: a novel platelet ADP P2Y12 receptor antagonist. AB - Novel adenosine diphosphate (ADP) P2Y(12) antagonists, including prasugrel, ticagrelor, cangrelor and elinogrel, are in various phases of clinical development. These ADP P2Y(12) antagonists have advantages over clopidogrel ranging from faster onset to greater and less variable inhibition of platelet function. Novel ADP P2Y(12) antagonists are under investigation to determine whether their use can result in improved antiplatelet activity, faster onset of action, and/or greater antithrombotic effects than clopidogrel, without an unacceptable increase in hemorrhagic or other side effects. Prasugrel (CS-747; LY 640315), a novel third-generation oral thienopyridine, is a specific, irreversible antagonist of the platelet ADP P2Y(12) receptor. Preclinical and early phase clinical studies have shown prasugrel to be characterized by more potent antiplatelet effects, lower interindividual variability in platelet response, and faster onset of activity compared to clopidogrel. Recent findings from large-scale phase III testing showed prasugrel to be more efficacious in preventing ischemic events in patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI); however, this is achieved at the expense of an increased risk of bleeding. Prasugrel provides more rapid and consistent platelet inhibition than clopidogrel. PMID- 20299392 TI - Seasonal variation, weekly and daily rhythm of transient ischemic attack in Hungary. PMID- 20299394 TI - Men behaving madly: testosterone replacement therapy. PMID- 20299396 TI - Sunbed use in children aged 11-17 in England: face to face quota sampling surveys in the National Prevalence Study and Six Cities Study. AB - OBJECTIVES: To quantify the use of sunbeds in young people across England, identify geographical variation, and explore patterns of use, including supervision. DESIGN: Two random location sampling surveys. SETTING: National Prevalence Study in England; Six Cities Study in Liverpool, Stoke/Stafford, Sunderland, Bath/Gloucester, Oxford/Cambridge, and Southampton. PARTICIPANTS: 3101 children aged 11-17 in the National Prevalence study and 6209 in the Six Cities study. RESULTS: In the National Prevalence Study 6.0% (95% confidence interval 5.1% to 6.8%) of those aged 11-17 had used a sunbed. Use was higher in girls than in boys (8.6% (7.2% to 10.0%) v 3.5% (2.6% to 4.4%), respectively), in those aged 15-17 compared with those aged 11-14 (11.2% (9.5% to 12.9%) v 1.8% (1.2% to 2.4%), respectively), and in those from lower rather than higher social grades (7.6% (5.7% to 9.5%) v 5.4% (4.5% to 6.3%), respectively). Sunbed use was higher in the "north" (11.0%, 8.9% to 13.0%) than in the "midlands" (4.2%, 2.5% to 5.8%) and the "south" (4.2%, 3.3% to 5.2%). In the Six Cities Study, sunbed use was highest in Liverpool and Sunderland (20.0% (17.5% to 22.4%) and 18.0% (15.6% to 20.3%), respectively), with rates especially high in girls, those aged 15-17, or from lower social grades. Mean age of first use was 14, and 38.4% (34.7% to 42.1%) of children used a sunbed at least once a week. Nearly a quarter (23.0%, 19.8% to 26.1%) of children had used a sunbed at home (including home of friends/relatives), and 24.7% (21.0% to 28.4%) said they had used sunbeds unsupervised in a tanning/beauty salon or gym/leisure centre. CONCLUSIONS: Sunbed use by children is widespread in England, is often inadequately supervised, and is a health risk. National legislation is needed to control sunbed outlets. PMID- 20299397 TI - Reducing sunbed use in young people. PMID- 20299400 TI - Ribulose-1,5-bisphosphate carboxylase/oxygenase genes as a functional marker for chemolithoautotrophic halophilic sulfur-oxidizing bacteria in hypersaline habitats. AB - The presence and diversity of the cbb genes encoding the large subunit of ribulose-1,5-bisphosphate carboxylase/oxygenase (RuBisCO) (a key enzyme of the Calvin-Benson cycle of autotrophic CO(2) assimilation) were investigated in pure cultures of seven genera of halophilic chemolithoautotrophic sulfur-oxidizing bacteria (SOB) and in sediments from a hypersaline lake in which such bacteria have been recently discovered. All of the halophilic SOB strains (with the exception of Thiohalomonas nitratireducens) possessed the cbbL gene encoding RuBisCO form I, while the cbbM gene encoding RuBisCO form II was detected only in some of the pure cultures. The general topologies of the CbbL/CbbM trees and the 16S rRNA gene tree were different, but both markers showed that the halophilic SOB genera formed independent lineages in the Gammaproteobacteria. In some cases, such as with several strains of the genus Thiohalospira and with Thioalkalibacter halophilus, the cbbL clustering was incongruent with the positions of these strains on the ribosomal tree. In the cbbM tree, the clustering of Thiohalospira and Thiohalorhabdus strains was incongruent with their branching in both cbbL and 16S rRNA gene trees. cbbL and cbbM genes related to those found in the analysed halophilic SOB were also detected in a sediment from a hypersaline lake in Kulunda Steppe (Russia). Most of the cbbL and cbbM genes belonged to members of the genus Thiohalorhabdus. In the cbbL clone library, sequences related to those of Halothiobacillus and Thiohalospira were detected as minor components. Some of the environmental cbbM sequences belonged to as yet unknown phylotypes, representing deep lineages of halophilic autotrophs. PMID- 20299401 TI - Effect of alkaline growth pH on the expression of cell envelope proteins in Fusobacterium nucleatum. AB - Fusobacterium nucleatum is a Gram-negative anaerobic organism that plays a central role in the development of periodontal diseases. The progression of periodontitis is associated with a rise in pH of the gingival sulcus which promotes the growth and expression of virulence factors by periodontopathic bacteria. We have previously reported that the expression of specific cytoplasmic proteins is altered by a shift in growth pH. In the present study we have compared cell envelope protein expression of F. nucleatum during chemostat growth at pH 7.2 and 7.8. From a total of 176 proteins resolved from the cell envelope, 15 were found to have altered expression in response to an increase in growth pH and were identified by MS. Upregulated proteins included an outer membrane porin which has been identified as playing a role in virulence, a periplasmic chaperone which assists in the folding of outer membrane proteins, and a transporter thought to be involved with iron uptake. Proteins downregulated at pH 7.8 were consistent with our previous findings that the bacterium reduces its catabolism of energy-yielding substrates in favour of energy-storage pathways. Among the downregulated proteins, two transporters which are involved in the uptake of C4 dicarboxylates and phosphate were identified. A putative protease and an enzyme associated with the metabolism of glutamate were also identified. A high proportion of the cell envelope proteins suggested by these data to play a role in the organism's response to alkaline growth pH may have arisen by lateral gene transfer. This would support the hypothesis that genes that provide an ability to adapt to the changing conditions of the oral environment may be readily shared between oral bacteria. PMID- 20299402 TI - Comparison of promoter-specific events during transcription initiation in mycobacteria. AB - DNA-protein interactions that occur during transcription initiation play an important role in regulating gene expression. To initiate transcription, RNA polymerase (RNAP) binds to promoters in a sequence-specific fashion. This is followed by a series of steps governed by the equilibrium binding and kinetic rate constants, which in turn determine the overall efficiency of the transcription process. We present here the first detailed kinetic analysis of promoter-RNAP interactions during transcription initiation in the sigma(A) dependent promoters P(rrnAPCL1), P(rrnB) and P(gyr) of Mycobacterium smegmatis. The promoters show comparable equilibrium binding affinity but differ significantly in open complex formation, kinetics of isomerization and promoter clearance. Furthermore, the two rrn promoters exhibit varied kinetic properties during transcription initiation and appear to be subjected to different modes of regulation. In addition to distinct kinetic patterns, each one of the housekeeping promoters studied has its own rate-limiting step in the initiation pathway, indicating the differences in their regulation. PMID- 20299403 TI - Hydrogen peroxide induces apoptosis-like death in Entamoeba histolytica trophozoites. AB - Programmed cell death (PCD) is an essential process in the growth and development of multicellular organisms. However, accumulating evidence indicates that unicellular eukaryotes can also undergo PCD with apoptosis-like features. This study demonstrates that after exposure to 0.8 mM H(2)O(2) for 9 h Entamoeba histolytica presents morphological and biochemical evidence of apoptosis-like death. Morphological characteristics of apoptosis-like death including DNA fragmentation, increased vacuolization, nuclear condensation and cell rounding were observed for H(2)O(2)-exposed trophozoites with preservation of membrane integrity. Biochemical alteration in ion fluxes is also a key feature in PCD, and H(2)O(2)-exposed trophozoites showed overproduction of reactive oxygen species, increased cytosolic Ca(2+) and decreased intracellular pH. Phosphatidylserine was also found to be expressed in the outer leaflet of the plasma membrane of the H(2)O(2)-treated trophozoites. Pretreatment with the cysteine protease inhibitor E-64d, the extracellular and intracellular Ca(2+) chelators EGTA and BAPTA/AM, and the Ca(2+) influx inhibitor verapamil prior to H(2)O(2) exposure abolished DNA fragmentation. The oxidatively stressed trophozoites also showed an increased calpain activity, indicating involvement of Ca(2+)-dependent calpain-like cysteine proteases in PCD of E. histolytica. A homogeneous caspase assay showed no significant caspase activity, and administration of caspase 1 inhibitor also did not prevent the death phenotype for the oxidatively stressed trophozoites, indicating a caspase-independent apoptosis-like death. Our observations clearly demonstrate that there is a distinct calpain-dependent but caspase-independent pathway for apoptosis-like death in oxidatively stressed E. histolytica trophozoites. PMID- 20299404 TI - The high-adhesive properties of the FimH adhesin of Salmonella enterica serovar Enteritidis are determined by a single F118S substitution. AB - The binding properties of low- and high-adhesive forms of FimH adhesins from Salmonella enterica serovars Enteritidis and Typhimurium (S. Enteritidis and S. Typhimurium) were studied using chimeric proteins containing an additional peptide that represents an N-terminal extension of the FimF protein. This modification, by taking advantage of a donor strand exchange mechanism, closes the hydrophobic groove in the fimbrial domain of the FimH adhesin. Such self complemented adhesins (scFimH) did not form aggregates and were more stable (resistant to proteolytic cleavage) than native FimH. High-adhesive variants of scFimH proteins, with alanine at position 61 and serine at position 118, were obtained by site-directed mutagenesis of fimH genes from low-adhesive variants of S. Enteritidis and S. Typhimurium, with glycine at position 61 and phenylalanine at position 118. Direct kinetic analysis using surface plasmon resonance (SPR) and glycoproteins carrying high-mannose carbohydrate chains (RNase B, horseradish peroxidase and mannan-BSA) revealed the existence of high- and low-adhesive allelic variants, not only in S. Typhimurium but also in S. Enteritidis. Using two additional mutants of low-adhesive FimH protein from S. Enteritidis (Gly61Ala and Phe118Ser), SPR analysis pointed to Ser118 as the major determinant of the high-adhesive phenotype of type 1 fimbriae from S. Enteritidis. These studies demonstrated for the first time that the functional differences observed with whole fimbriated bacteria could be reproduced at the level of purified adhesin. They strongly suggest that the adhesive properties of type 1 fimbriae are determined only by structural differences in the FimH proteins and are not influenced by the fimbrial shaft on which the adhesin is located. PMID- 20299405 TI - Identification of Rhodococcus equi lipids recognized by host cytotoxic T lymphocytes. AB - Immune adult horses have CD8(+) cytotoxic T lymphocytes (CTLs) that recognize and lyse Rhodococcus equi-infected cells in an equine lymphocyte alloantigen (ELA)-A [classical major histocompatibility complex (MHC) class I]-unrestricted fashion. As protein antigens are MHC class I-restricted, the lack of restriction suggests that the bacterial antigens being recognized by the host are not proteins. The goals of this study were to test the hypothesis that these CTLs recognize unique R. equi cell-wall lipids related to mycobacterial lipids. Initial experiments showed that treatment of soluble R. equi antigen with broadly reactive proteases did not significantly diminish the ability of the antigen to stimulate R. equi specific CTLs. R. equi-specific CTLs were also shown to lyse target cells (equine macrophages) pulsed with an R. equi lipid extract. Analysis of the R. equi lipid by TLC and MS (MALDI-TOF and ES) indicated that the extracted antigen consisted of three primary fractions: trehalose monomycolate (TMM), trehalose dimycolate (TDM) and cardiolipin (CL). ELA-A-mismatched cells pulsed with purified TMM and CL, but not the TDM fraction, were recognized and lysed by R. equi-specific CTLs. Because of their role in immune clearance and pathogenesis, transcription of the cytokines gamma interferon (IFN-gamma) and interleukin-4 (IL-4) was also measured in response to R. equi lipids by using real-time PCR; elevated IFN-gamma, but not IL-4, was associated with host clearance of the bacteria. The whole-cell R. equi lipid and all three R. equi lipid fractions resulted in marked increases in IFN gamma transcription, but no increase in IL-4 transcription. Together, these data support the hypothesis that immune recognition of unique lipids in the bacterial cell wall is an important component of the protective immune response to R. equi. The results also identify potential lipid antigens not previously shown to be recognized by CTLs in an important, naturally occurring actinomycete bacterial pathogen. PMID- 20299406 TI - The Hem and Has haem uptake systems in Serratia marcescens. AB - Serratia marcescens, like several other Gram-negative bacteria, possesses two functional haem uptake systems. The first, referred to as the Hem system, can transport haem present at a concentration equal to or above 10(-6) M. It requires an active outer-membrane receptor which uses proton-motive force energy transmitted by the inner-membrane TonB protein. The other system, Has, takes up haem at lower concentrations and utilizes a small secreted haem-binding protein (haemophore) and its cognate TonB-dependent outer-membrane receptor HasR. Various combinations of mutations were used to examine haem uptake activity by the two systems in S. marcescens. The Hem uptake system enables S. marcescens to take up haem at a concentration of 10(-6) M in the presence of various levels of iron depletion. The Has system, which enables such uptake even in the presence of lower haem concentrations, requires higher iron depletion conditions for function. Has haem uptake requires the presence of HasB, a TonB paralogue encoded by the has operon. These two systems enable S. marcescens to take up haem under various conditions from different sources, reflecting its capacity to confront conditions encountered in natural biotopes. PMID- 20299407 TI - Spondyloarthritis in a patient with unilateral buttock pain and history of Crohn disease. AB - BACKGROUND AND PURPOSE: Patients with inflammatory spinal conditions related to spondyloarthritis are rarely seen by primary care practitioners. However, patients with a history of inflammatory bowel disease and chronic low back or buttock pain should be examined carefully for the presence of spondyloarthritis, as proper management may include referral to a rheumatologist and appropriate medical intervention. CASE DESCRIPTION: A 27-year-old woman with a 6-month history of posterior buttock pain was referred for physical therapy with a diagnosis of piriformis syndrome. During the second physical therapy visit, a nonmechanical source of lumbopelvic pain was suspected, and the patient was referred for medical consultation. The patient underwent evaluation by a rheumatologist and was eventually diagnosed with spondyloarthritis associated with inflammatory bowel disease. OUTCOMES: The patient initiated treatment with anti-tumor necrosis factor medication to address the spondyloarthritis. Medical management resulted in significant improvement in all outcome measures. DISCUSSION: Clinical suspicion of spondyloarthritis is raised when specific historical, examination, and imaging findings are present. The posttest probability of spondyloarthritis is increased with the presence of inflammatory back pain and specific spondyloarthritic features, such as a positive history of inflammatory bowel disease, radiographic evidence of sacroiliitis, and improvement with anti-inflammatory medication. Referral of patients with these findings for a rheumatological evaluation is warranted, as these diseases are managed effectively with specific treatment. PMID- 20299408 TI - Physical therapists' perceptions of ease of care in patients receiving 2 forms of analgesia after total hip arthroplasty. AB - BACKGROUND: Pain management modalities that facilitate patient mobility may contribute to recovery after total hip replacement (THR) surgery. OBJECTIVE: The aim of this study was to evaluate the impact of morphine intravenous (IV) patient controlled analgesia (PCA) and the fentanyl iontophoretic transdermal system (fentanyl ITS) on physical therapists' ability to complete care tasks for patients after THR. DESIGN: The data were from an open-label, randomized, multicenter, active-control phase IIIb clinical trial. METHODS: The settings were 52 US-based teaching and community hospitals. The patients were >or=18 years of age (mean [SEM]: 62.8 [0.6] years in the fentanyl ITS group and 62.9 [0.6] years in the morphine IV PCA group); had an American Society of Anesthesiologists physical status of I, II, or III; and were scheduled to undergo primary unilateral THR surgery. The patients were randomized to receive analgesia for up to 72 hours via the fentanyl ITS (40 microg of fentanyl over 10 minutes for up to 6 doses per hour for 24 hours or 80 doses per system, whichever occurred first) or morphine IV PCA (1-mg bolus doses [with a 5-minute lockout interval between doses] for up to 10 doses per hour for 24 hours). All patients received the usual treatment administered by physical therapists. After each therapy session, physical therapists completed a validated Physical Therapist Ease-of-Care Questionnaire, which included time efficiency and convenience subscales (lower scores indicated more positive responses) and a satisfaction subscale (a higher score indicated a more positive response). Therapists whose average scores were or=4 on both items of the satisfaction subscale were considered responders. RESULTS: Higher percentages of physical therapists were responders for the fentanyl ITS than for morphine IV PCA on the subscales that assessed time efficiency (84.9% and 59.1%, respectively), convenience (86.6% and 71.2%, respectively), and satisfaction (54.3% and 30.5%, respectively). Higher percentages of physical therapists favored the fentanyl ITS than favored morphine IV PCA. Limitations The trial was limited by its open-label design, and physical therapists were more familiar with IV PCA than with the fentanyl ITS. CONCLUSIONS: The findings demonstrate benefits to physical therapists of using the fentanyl ITS over morphine IV PCA in terms of time efficiency, convenience, and satisfaction. PMID- 20299409 TI - Ongoing walking recovery 2 years after locomotor training in a child with severe incomplete spinal cord injury. AB - BACKGROUND AND PURPOSE: The authors previously reported on walking recovery in a nonambulatory child with chronic, severe, incomplete cervical spinal cord injury (SCI) after 76 sessions of locomotor training (LT). Although clinical measures did not predict his recovery, reciprocal patterned leg movements developed, affording recovery of independent walking with a reverse rolling walker. The long term functional limitations and secondary complications often associated with pediatric-onset SCI necessitate continued follow-up of children with SCI. Therefore, the purpose of this case report is to describe this child's walking function and musculoskeletal growth and development during the 2 years since his participation in an LT program and subsequent walking recovery. CASE DESCRIPTION: Following LT, the child attended elementary school as a full-time ambulator. He was evaluated 1 month (baseline), 1 year, and 2 years after LT. Examination of walking function included measures of walking independence, gait speed and spatiotemporal parameters, gait kinematics, and daily step activity. Growth and development were assessed by tracking his height, weight, incidence of musculoskeletal complications, and gross motor task performance. OUTCOMES: Over the 2 years, the child continued to ambulate independently with a reverse rolling walker, increasing his fastest gait speed. Spatiotemporal and kinematic features of his walking improved, and daily step activity increased. Height and weight remained on their preinjury trajectory and within age-appropriate norms. The child experienced only minor musculoskeletal complications. Additionally, he gained the ability to use reciprocal patterned leg movements during locomotor tasks such as assisted stair climbing and independent tricycle pedaling. CONCLUSIONS: Two years after recovery of walking, this child with incomplete SCI had maintained and improved his walking function and experienced age-appropriate growth and development. PMID- 20299411 TI - Do as I do: exercise habits of physical therapists, physical therapist assistants, and student physical therapists. AB - BACKGROUND: Physical therapy practitioners are among the many health care professionals who can counsel their patients to address the public health care concern of physical inactivity. Health care providers who are physically active themselves are more likely to counsel patients on the benefits of activity. OBJECTIVE: The purposes of this study were: (1) to examine the leisure-time physical activity habits of physical therapists, physical therapist assistants, and student physical therapists in the United States using Centers for Disease Control and Prevention and American College of Sports Medicine (CDC-ACSM) recommendations and (2) to compare these habits with those of the general population and other health care professionals. DESIGN: A cross-sectional survey design was used. METHODS: There were 2 data sources. A random sample of American Physical Therapy Association members completed an online survey that included questions about physical activity habits worded in same manner as the leisure time activities section of the 2005 National Health Interview Survey (NHIS). The final study sample comprised 1,238 participants: 923 physical therapists, 210 student physical therapists, and 105 physical therapist assistants. The 2005 NHIS public use data files were the source for the same information about the general US population and for a subset of health care professionals. Rates of participation in vigorous and moderate physical activity were analyzed. RESULTS: Physical therapists, physical therapist assistants, and student physical therapists exercised at higher rates than adults and health-diagnosing professionals in the 2005 NHIS. Limitations The study may be limited by sampling and response bias. CONCLUSIONS: This study identified that physical therapists, physical therapist assistants, and student physical therapists are meeting CDC ACSM physical activity guidelines at higher rates than the US adult population and health-diagnosing professionals. These rates exceed the physical activity targets set for adults in Healthy People 2010. PMID- 20299410 TI - Physical therapists make accurate and appropriate discharge recommendations for patients who are acutely ill. AB - BACKGROUND: Acute care physical therapists contribute to the complex process of patient discharge planning. As physical therapists are experts at evaluating functional abilities and are able to incorporate various other factors relevant to discharge planning, it was expected that physical therapists' recommendations of patient discharge location would be both accurate and appropriate. OBJECTIVE: This study determined how often the therapists' recommendations for patient discharge location and services were implemented, representing the accuracy of the recommendations. The impact of unimplemented recommendations on readmission rate was examined, reflecting the appropriateness of the recommendations. DESIGN: This retrospective study included the discharge recommendations of 40 acute care physical therapists for 762 patients in a large academic medical center. The frequency of mismatch between the physical therapist's recommendation and the patient's actual discharge location and services was calculated. The mismatch variable had 3 levels: match, mismatch with services lacking, or mismatch with different services. Regression analysis was used to test whether mismatch status, patient age, length of admission, or discharge location predicted patient readmittance. RESULTS: Overall, physical therapists' discharge recommendations were implemented 83% of the time. Patients were 2.9 times more likely to be readmitted when the therapist's discharge recommendation was not implemented and recommended follow-up services were lacking (mismatch with services lacking) compared with patients with a match. Limitations This study was limited to one facility. Limited information about the patients was collected, and data on patient readmission to other facilities were not collected. CONCLUSIONS: This study supports the role of physical therapists in discharge planning in the acute care setting. Physical therapists demonstrated the ability to make accurate and appropriate discharge recommendations for patients who are acutely ill. PMID- 20299412 TI - Which lipid fraction is the target and how often should this be monitored? PMID- 20299413 TI - Current status of percutaneous coronary intervention in China. PMID- 20299414 TI - Gender perspective on risk factors, coronary lesions and long-term outcome in young patients with ST-elevation myocardial infarction. AB - OBJECTIVE: Previous data on young patients with acute coronary syndrome (ACS) have indicated higher rates of normal coronary angiograms but higher mortality in women than men. However, ST-elevation myocardial infarction (STEMI) differs from non-ST-elevation ACS in many aspects. We elucidated sex differences in risk factors, angiographic findings and outcome in consecutive STEMI patients below 46 years of age. DESIGN: Retrospective cohort study. SETTING: The Swedish registers for CCU care and coronary angioplasty; RIKS-HIA and SCAAR. PATIENTS: 2132 STEMI patients below 46 years of age admitted to intensive coronary care units in Sweden between 1995 and 2006 and followed for at least 1 year. MAIN OUTCOME MEASURES: Angiographic findings and short-term and long-term mortality. RESULTS: Risk factors were more common in women. Significant coronary lesions were equally common (92.1% vs 93.1%, p=0.64) while single vessel disease was more common (72.9% vs 59.3%; p<0.001) in women. Women had higher multivariable adjusted in hospital mortality, OR 2.85 (95% CI 1.31 to 6.19) while long-term mortality was the same, HR 0.93 (95% CI 0.60 to 1.45). The catch-up of mortality in men might be related to a higher occurrence of re-infarctions, HR 1.82 (95% CI 1.25 to 2.65). CONCLUSIONS: STEMI below age 46 is a more rare condition in women than in men and more often related to cardiovascular risk factors. More than 90% of both men and women had coronary lesions, in women more often single vessel lesions. Female sex is associated with higher in-hospital mortality, while long-term mortality is low without difference between genders. PMID- 20299415 TI - Septic palmar emboli in a case of staphylococcal aortic endocarditis. PMID- 20299417 TI - Response to Bhaskaran et al's "Effects of air pollution on the incidence of myocardial infarction". PMID- 20299420 TI - Prevention of cardiovascular disease in asymptomatic people. PMID- 20299419 TI - Inherited cardiovascular conditions: the challenges of genomic medicine. AB - The report Heart to Heart published in 2009 by the Foundation for Genomics and Population Health provided an account of new health services needs arising from greater scientific and clinical understanding of inherited cardiovascular conditions. Informed by advice from an expert working group, the report makes recommendations for the development of specialised inherited cardiovascular conditions services within the UK. The report will also be of relevance internationally, wherever cardiologists and geneticists aim to provide care for these patients and their families. PMID- 20299421 TI - Post-myocardial infarction biventricular pseudoaneurysm with bidirectional shunt. PMID- 20299422 TI - Acute myocardial infarction due to paradoxical embolism: successful catheter aspiration and histological correlation. PMID- 20299423 TI - Comparison of orthodontic treatment need by professionals and parents with different socio-demographic characteristics. AB - The aim of this study was to compare the socio-demographic features and self perception of parents concerning the malocclusion of their children with the orthodontist's opinion of normative orthodontic treatment need. The parents of 208 children (101 girls and 107 boys, between 9 and 18 years: mean 12.8 +/- 2.5), who sought orthodontic treatment were asked to score the dental attractiveness of their children using the aesthetic component (AC) of the Index of Orthodontic Treatment Need (IOTN). These scores were then compared with those of the orthodontist, who also scored the Dental Health Component (DHC) of the IOTN. The influence of the socio-demographic features of the parents on both the orthodontist- and parent-rated IOTN scores was assessed. The AC grade of the IOTN and patient characteristics were tested with the Spearman's correlation coefficient (rho). The difference between the two dependent variables (orthodontists' and parents' AC grade) was compared using Wilcoxon's test. A high need for orthodontic treatment was recorded in 74.0 per cent of the subjects. Although orthodontists rated 51.4 per cent of the patients as having a severe malocclusion on aesthetic grounds, only 33.6 per cent of parents rated their child malocclusion as severe. Although socio-demographic factors were not related to the parents' perception of malocclusion, they had an influence on orthodontic treatment need as assessed by the orthodontist. Parents, in this study population, rated their children's orthodontic treatment need less severely than the orthodontist regardless of their socio-demographic characteristics. Thus, orthodontists should involve parents in the orthodontic treatment decision-making process. PMID- 20299425 TI - Private long-term care insurance: value to claimants and implications for long term care financing. AB - PURPOSE: The purpose of this study was to obtain a profile of individuals with private long-term care (LTC) insurance as they begin using paid LTC services and track their patterns of service use, satisfaction with services and insurance, claims denial rates, and transitions over a 28-month period. DESIGN AND METHODS: Ten LTC insurance companies contributed a random sample of 1,474 qualified individuals who were interviewed in-person by a trained nurse and then interviewed telephonically every 4 month for a 28-month period. Used in the analysis were descriptive statistics and techniques for analyzing longitudinal panel data. RESULTS: About 96% of those filing claims were approved for payment. At baseline, 37% received home care, 23% assisted living care, 14% were in a nursing home, and 26% had not yet begun using paid care. Few claimants reported that their policies restricted their choice of providers and most care costs were covered. The average number of care transitions was 1, typically occurring within 4 month of baseline. The less impaired and those in home care settings were most likely to transition between service settings. IMPLICATIONS: Having private LTC coverage enabled claimants to exercise their preference for alternatives to nursing home care. PMID- 20299424 TI - Regulation of human organic anion transporter 3 by peptide hormone bradykinin. AB - Human organic anion transporter (hOAT) 3 belongs to a family of organic anion transporters that play critical roles in the body disposition of numerous clinically important drugs. In the current study, we examined the regulation of hOAT3 by peptide hormone bradykinin (BK) in COS-7 cells. BK (73 years) and aMCI-young (3 cm at chest X ray) persisting over three days after major lung resection were enrolled in this study. All patients were treated with combined pneumoperitoneum and autologus blood patch. Pneumoperitoneum is obtained by the injection of 30 ml/kg of air under the diaphragm, using a Verres needle through the periumbilical area. The blood patch is obtained by instillating 100 ml of autologus blood through the chest tubes. No patients experienced complications related to the procedure. Obliteration of pleural space was obtained in all the patients at a maximum of 96 h postoperatively. Air leaks stopped in all the cases at a maximum of 144 h from surgery. Chest tube was removed 24 h after the air leakage disappearance. Our 10 year experience supports the early, combined use of pneumoperitoneum and blood patch whenever pleural space and air leaks present after major pulmonary resection. This approach may be recommended because of its easiness, safety, effectiveness, and the low costs. PMID- 20299445 TI - Video-assisted thoracic surgery for pulmonary aspergilloma. AB - The purpose of this retrospective study was to review our experience with video assisted thoracic surgery (VATS) for pulmonary aspergilloma. The patients (n=20) were aged 62+/-12 years, and eight (40%) were aged 70 years or more. The disease types were simple aspergilloma (SA) in six patients and complex aspergilloma (CA) in 14. The surgical procedures performed were lobectomy in 14 patients, segmentectomy in two, and wedge resection in four. The operation time was shorter (143+/-69 min vs. 216+/-85 min; P=0.08) and the blood loss was less (10+/-17 ml vs. 307+/-346 ml; P<0.01) for patients with SA than those with CA. Postoperative death occurred in one patient with CA who developed a bronchial stump fistula (30 day mortality; 5.0%). During follow-up, three patients died from other non disease-related causes, and the remaining 17 patients survived without recurrence. The 5-year survival rate was 89%. In suitable cases, VATS for pulmonary aspergilloma may not be inferior to open surgery with regard to safety and efficacy. In particular, SA is considered to be a good indication for VATS. PMID- 20299447 TI - Iatrogenic type A aortic dissection during cardiac surgery. AB - We reviewed our experience of intraoperative type A aortic dissection during cardiovascular surgery. From January 1998 to May 2009, intraoperative aortic dissection occurred in 10 of 3421 cardiac surgical patients (M:F=4:6, 62.4+/-8.0 years). Preoperative diagnoses were valvular heart disease (n=6), ischemic heart disease (n=2), combined disease (n=1) and aortic aneurysm (n=1). All underwent total circulatory arrest (TCA) with retrograde cerebral perfusion and the torn aorta was replaced (n=8) or repaired (n=2). Iatrogenic type A dissection occurred in 0.29% of patients. It was related with cannulation of ascending aorta (n=4), axillary artery (n=2), aortic root (n=2), and femoral artery (n=1) and aortotomy repair (n=1). Mortality rate was 40% (4/10). After adoption of routine intraoperative transesophageal echocardiography, mortality rate decreased from 75% (3/4) to 17% (1/6) (P=0.190). We initiated TCA before achieving deep hypothermia in three of four non-survivors. There was a trend of increased mortality when the disease extended beyond aortic arch (67%, 4/6 vs. 0%, 0/4; P=0.076). Although intraoperative aortic dissection occurred in <0.3% of our patient population, mortality was high, especially when it extended beyond the arch vessels. Better results were expected when early recognition and proper treatment under deep hypothermic circulatory arrest could be performed. PMID- 20299449 TI - A chromodomain switch mediated by histone H3 Lys 4 acetylation regulates heterochromatin assembly. AB - Chromodomain proteins (Chp1/Chp2/Swi6/Clr4) bind to methylated H3K9 (H3K9me) and regulate pericentric heterochromatin in fission yeast. Chp1 and Clr4 (H3K9-HMT), bind transcriptionally active heterochromatin, whereas Chp2/Swi6 (HP1 homologs) are recruited during the inactive state. We show that H3K4 acetylation (H3K4ac) plays a role in the transition of dimethylated H3K9 (H3K9me2) occupancy from Chp1/Clr4 to Chp2/Swi6. H3K4ac, mediated by Mst1, is enriched at pericentromeres concomitantly with heterochromatin reassembly. H3K4R (Lys --> Arg) mutation increases Chp1 and decreases Chp2/Swi6 pericentric occupancy and exhibits centromeric desilencing. Consistent with structural data, H3K4ac specifically reduces Chp1/Clr4 affinity to H3K9me. We propose that H3K4ac mediates a chromodomain switch from Chp1/Clr4 to Swi6/Chp2 to allow heterochromatin reassembly. PMID- 20299448 TI - MicroRNAs coordinate an alternative splicing network during mouse postnatal heart development. AB - Alternative splicing transitions have been identified recently as a conserved component of vertebrate heart remodeling during postnatal development. Here we report that the targeted deletion of Dicer, specifically in adult mouse myocardium, reveals the role of microRNAs (miRNAs) in regulating networks of postnatal splicing transitions and in maintaining adult splicing programs. We demonstrate a direct role for miR-23a/b in the dramatic postnatal down-regulation of CUGBP and ETR-3-like factor (CELF) proteins that regulate nearly half of developmentally regulated splicing transitions in the heart. These findings define a hierarchy in which rapid postnatal up-regulation of specific miRNAs controls expression of alternative splicing regulators and the subsequent splicing transitions of their downstream targets. PMID- 20299450 TI - The communication skills used by deaf children and their hearing peers in a question-and-answer game context. AB - Communication is frequently characterized by a sequence of questions and answers. Little is known about how well students who are deaf or hard of hearing (deaf/HH) understand their hearing classmates in the context of an inclusive setting. This study explored the communication skills used by deaf/HH children when asking and answering questions in a "trivia" game with their hearing peers. Thirty-four children with normal hearing and 34 children with a hearing loss ranging from mild to profound (>90 dB HL) participated in this study. Each of the 34 dyads included 1 child with normal hearing and 1 child with hearing loss, matched by gender and grade level at school. Dyads were videotaped and analyzed. Pairs were compared in terms of their capacity to repeat the question, strategies used to seek information, and accuracy of responses. Results showed that the group of hearing children was able to repeat more questions verbatim compared to the deaf/HH children. The deaf/HH group required a significantly greater number of repetitions, sought a greater number of general clarifications, and correctly answered more questions compared with the group of hearing children. The implications of these findings are discussed in terms of peer communication and pragmatic skill development. PMID- 20299451 TI - Human CRB2 inhibits gamma-secretase cleavage of amyloid precursor protein by binding to the presenilin complex. AB - Drosophila Crumbs has been reported to attenuate Notch signaling by inhibition of gamma-secretase cleavage at the wing margins. gamma-Secretase is an intramembrane protease that is responsible for the generation of amyloid-beta (Abeta) peptides from the beta-amyloid precursor protein (APP). Here, we re-examined gamma secretase inhibition by human CRB2, which is the most abundant Crumbs ortholog in the brain. Transfected CRB2 inhibited proteolytic production of Abeta and APP intracellular domains from APP C-terminal fragments in HEK293 and SH-SY5Y cells. Conversely, knockdown of endogenous CRB2 increased gamma-secretase cleavage products in SH-SY5Y cells. CRB2 inhibition of gamma-cleavage was also detected in cell-free assays. CRB2 interacted with the gamma-secretase complex, but was not a competitive substrate for gamma-cleavage. The transmembrane domain of CRB2 was indispensable for inhibition of Abeta generation and mediated CRB2 binding with the gamma-secretase complex. In addition, the cytoplasmic domain appeared to play a supportive role in gamma-secretase inhibition, whereas mutational disruption of the two protein-binding motifs involved in the formation of cell adhesion complexes did not affect gamma-secretase inhibition. Co-overexpression of presenilin-1 or APH-1 abrogated gamma-secretase inhibition probably through prevention of the incorporation of CRB2 into the gamma-secretase complex. Our results suggest that CRB2 functions as an inhibitory binding protein that is involved in the formation of a mature but inactive pool of the gamma-secretase complex. PMID- 20299452 TI - Crystal structures of human choline kinase isoforms in complex with hemicholinium 3: single amino acid near the active site influences inhibitor sensitivity. AB - Human choline kinase (ChoK) catalyzes the first reaction in phosphatidylcholine biosynthesis and exists as ChoKalpha (alpha1 and alpha2) and ChoKbeta isoforms. Recent studies suggest that ChoK is implicated in tumorigenesis and emerging as an attractive target for anticancer chemotherapy. To extend our understanding of the molecular mechanism of ChoK inhibition, we have determined the high resolution x-ray structures of the ChoKalpha1 and ChoKbeta isoforms in complex with hemicholinium-3 (HC-3), a known inhibitor of ChoK. In both structures, HC-3 bound at the conserved hydrophobic groove on the C-terminal lobe. One of the HC-3 oxazinium rings complexed with ChoKalpha1 occupied the choline-binding pocket, providing a structural explanation for its inhibitory action. Interestingly, the HC-3 molecule co-crystallized with ChoKbeta was phosphorylated in the choline binding site. This phosphorylation, albeit occurring at a very slow rate, was confirmed experimentally by mass spectroscopy and radioactive assays. Detailed kinetic studies revealed that HC-3 is a much more potent inhibitor for ChoKalpha isoforms (alpha1 and alpha2) compared with ChoKbeta. Mutational studies based on the structures of both inhibitor-bound ChoK complexes demonstrated that Leu-401 of ChoKalpha2 (equivalent to Leu-419 of ChoKalpha1), or the corresponding residue Phe-352 of ChoKbeta, which is one of the hydrophobic residues neighboring the active site, influences the plasticity of the HC-3-binding groove, thereby playing a key role in HC-3 sensitivity and phosphorylation. PMID- 20299453 TI - Expression of a G protein-coupled receptor (GPCR) leads to attenuation of signaling by other GPCRs: experimental evidence for a spontaneous GPCR constitutive inactive form. AB - The idea of G protein-coupled receptors (GPCRs) coupling to G protein solely in their active form was abolished when it was found that certain ligands induce a G protein-coupled but inactive receptor form. This receptor form interferes with signaling of other receptors by sequestering G protein. However, the spontaneous existence of this receptor species has never been established. The aim of the present work was to evaluate the existence of the spontaneous conformation of the receptor inactively coupled to G protein able to interfere with the response of other GPCRs. According to the law of mass action, receptor overexpression should lead to increased amounts of all spontaneously occurring species. Based on this, we generated Chinese hamster ovary (CHO-K1)-derived cell lines expressing various amounts of the human histamine H2 receptor. In these systems, the signaling of other endogenously and transiently expressed GPCRs was attenuated proportionally to human H2 receptor expression levels. G protein transfection specifically reverted this attenuation, strongly suggesting hijacking of the G protein from a common pool. Similar attenuation effects were observed when the beta(2)- adrenergic receptor was overexpressed, suggesting that this is a more general phenomenon. Moreover, in human mammary MDA-MB-231 cells, a consistent increase in the response of other GPCRs was observed when endogenous expression of beta(2) adrenergic receptor was knocked down using specific small interfering RNAs. Our findings show that GPCRs may interact with the signaling of other receptors by modulating the availability of the G protein and suggest the existence of GPCR spontaneous coupling to G proteins in an inactive form. PMID- 20299454 TI - Metabolic and transcriptional response to cofactor perturbations in Escherichia coli. AB - Metabolic cofactors such as NADH and ATP play important roles in a large number of cellular reactions, and it is of great interest to dissect the role of these cofactors in different aspects of metabolism. Toward this goal, we overexpressed NADH oxidase and the soluble F1-ATPase in Escherichia coli to lower the level of NADH and ATP, respectively. We used a global interaction network, comprising of protein interactions, transcriptional regulation, and metabolic networks, to integrate data from transcription profiles, metabolic fluxes, and the metabolite levels. We identified high-scoring networks for the two strains. The results revealed a smaller, but denser network for perturbations of ATP level, compared with that of NADH level. The action of many global transcription factors such as ArcA, Fnr, CRP, and IHF commonly involved both NADH and ATP, whereas others responded to either ATP or NADH. Overexpressing NADH oxidase invokes response in widespread aspects of metabolism involving the redox cofactors (NADH and NADPH), whereas ATPase has a more focused response to restore ATP level by enhancing proton translocation mechanisms and repressing biosynthesis. Interestingly, NADPH played a key role in restoring redox homeostasis through the concerted activity of isocitrate dehydrogenase and UdhA transhydrogenase. We present a reconciled network of regulation that illustrates the overlapping and distinct aspects of metabolism controlled by NADH and ATP. Our study contributes to the general understanding of redox and energy metabolism and should help in developing metabolic engineering strategies in E. coli. PMID- 20299455 TI - The fission yeast inhibitor of growth (ING) protein Png1p functions in response to DNA damage. AB - In budding yeast and human cells, ING (inhibitor of growth) tumor suppressor proteins play important roles in response to DNA damage by modulating chromatin structure through collaborating with histone acetyltransferase or histone deacetylase complexes. However, the biological functions of ING family proteins in fission yeast are poorly defined. Here, we report that Png1p, a fission yeast ING homolog protein, is required for cell growth under normal and DNA-damaged conditions. Png1p was further confirmed to regulate histone H4 acetylation through collaboration with the MYST family histone acetyltransferase 1 (Mst1). Additionally, both fission yeast PNG1 and MST1 can functionally complement their budding yeast correspondence homologs YNG2 and ESA1, respectively. These results suggest that ING proteins in fission yeast might also conserve function, similar to ING proteins in budding yeast and human cells. We also showed that decreased acetylation in Deltapng1 cells resulted in genome-wide down-regulation of 756 open reading frames, including the central DNA repair gene RAD22. Overexpression of RAD22 partially rescued the png1 mutant phenotype under both normal and DNA damaged conditions. Furthermore, decreased expression of RAD22 in Deltapng1 cells was confirmed to be caused by decreased H4 acetylation at its promoter. Altogether, these results indicate that Png1p is required for histone H4 acetylation and functions upstream of RAD22 in the DNA damage response pathway. PMID- 20299456 TI - Ligand-specific conformation of extracellular loop-2 in the angiotensin II type 1 receptor. AB - The orientation of the second extracellular loop (ECL2) is divergent in G-protein coupled receptor (GPCR) structures determined. This discovery provoked the question, is the ECL2 conformation differentially regulated in the GPCRs that respond to diffusible ligands? We have determined the conformation of the ECL2 of the angiotensin II type 1 receptor by reporter-cysteine accessibility mapping in different receptor states (i.e. empty, agonist-bound and antagonist-bound). We introduced cysteines at each position of ECL2 of an N-terminal epitope-tagged receptor surrogate lacking all non-essential cysteines and then measured reaction of these with a cysteine-reactive biotin probe. The ability of biotinylated mutant receptors to react with a steptavidin-HRP-conjugated antibody was used as the basis for examining differences in accessibility. Two segments of ECL2 were accessible in the empty receptor, indicating an open conformation of ECL2. These segments were inaccessible in the ligand-bound states of the receptor. Using the accessibility constraint, we performed molecular dynamics simulation to predict ECL2 conformation in different states of the receptor. Analysis suggested that a lid conformation similar to that of ECL2 in rhodopsin was induced upon binding both agonist and antagonist, but exposing different accessible segments delimited by the highly conserved disulfide bond. Our study reveals the ability of ECL2 to interact with diffusing ligands and to adopt a ligand-specific lid conformation, thus, slowing down dissociation of ligands when bound. Distinct conformations induced by the bound agonist and the antagonist around the conserved disulfide bond suggest an important role for this disulfide bond in producing different functional states of the receptor. PMID- 20299457 TI - Oxidants positively or negatively regulate nuclear factor kappaB in a context dependent manner. AB - Redox-based mechanisms play critical roles in the regulation of multiple cellular functions. NF-kappaB, a master regulator of inflammation, is an inducible transcription factor generally considered to be redox-sensitive, but the modes of interactions between oxidant stress and NF-kappaB are incompletely defined. Here, we show that oxidants can either amplify or suppress NF-kappaB activation in vitro by interfering both with positive and negative signals in the NF-kappaB pathway. NF-kappaB activation was evaluated in lung A549 epithelial cells stimulated with tumor necrosis factor alpha (TNFalpha), either alone or in combination with various oxidant species, including hydrogen peroxide or peroxynitrite. Exposure to oxidants after TNFalpha stimulation produced a robust and long lasting hyperactivation of NF-kappaB by preventing resynthesis of the NF kappaB inhibitor IkappaB, thereby abrogating the major negative feedback loop of NF-kappaB. This effect was related to continuous activation of inhibitor of kappaB kinase (IKK), due to persistent IKK phosphorylation consecutive to oxidant mediated inactivation of protein phosphatase 2A. In contrast, exposure to oxidants before TNFalpha stimulation impaired IKK phosphorylation and activation, leading to complete prevention of NF-kappaB activation. Comparable effects were obtained when interleukin-1beta was used instead of TNFalpha as the NF-kappaB activator. This study demonstrates that the influence of oxidants on NF-kappaB is entirely context-dependent, and that the final outcome (activation versus inhibition) depends on a balanced inhibition of protein phosphatase 2A and IKK by oxidant species. Our findings provide a new conceptual framework to understand the role of oxidant stress during inflammatory processes. PMID- 20299459 TI - Dicalcin inhibits fertilization through its binding to a glycoprotein in the egg envelope in Xenopus laevis. AB - Fertilization comprises oligosaccharide-mediated sperm-egg interactions, including sperm binding to an extracellular egg envelope, sperm penetration through the envelope, and fusion with an egg plasma membrane. We show that Xenopus dicalcin, an S100-like Ca(2+)-binding protein, present in the extracellular egg envelope (vitelline envelope (VE)), is a suppressive mediator of sperm-egg interaction. Preincubation with specific antibody greatly increased the efficiency of in vitro fertilization, whereas prior application of exogenous dicalcin substantially inhibited fertilization as well as sperm binding to an egg and in vitro sperm penetration through the VE protein layer. Dicalcin showed binding to protein cores of gp41 and gp37, constituents of VE, in a Ca(2+) dependent manner and increased in vivo reactivity of VE with a lectin, Ricinus communis agglutinin I, which was accounted for by increased binding ability of gp41 to the lectin and greater exposure of gp41 to an external environment. Our findings strongly suggest that dicalcin regulates the distribution of oligosaccharides within the VE through its binding to the protein core of gp41, probably by modulating configuration of oligosaccharides on gp41 and the three dimensional structure of VE framework, and thereby plays a pivotal role in sperm egg interactions during fertilization. PMID- 20299458 TI - The RNA polymerase-associated factor 1 complex (Paf1C) directly increases the elongation rate of RNA polymerase I and is required for efficient regulation of rRNA synthesis. AB - The rate of ribosome synthesis is proportional to the rate of cell proliferation; thus, transcription of rRNA by RNA polymerase I (Pol I) is an important target for the regulation of this process. Most previous investigations into mechanisms that regulate the rate of ribosome synthesis have focused on the initiation step of transcription by Pol I; however, recent studies in yeast and mammals have identified factors that influence transcription elongation by Pol I. The RNA polymerase-associated factor 1 complex (Paf1C) is a transcription elongation factor with known roles in Pol II transcription. We previously identified a role for Paf1C in transcription elongation by Pol I. In this study, genetic interactions between genes for Paf1C and Pol I subunits confirm this conclusion. In vitro studies demonstrate that purified Paf1C directly increases the rate of transcription elongation by Pol I. Finally, we show that Paf1C function is required for efficient control of Pol I transcription in response to target of rapamycin (TOR) signaling or amino acid limitation. These studies demonstrate that Paf1C plays an important direct role in cellular control of rRNA expression. PMID- 20299460 TI - Allosteric drug discrimination is coupled to mechanochemical changes in the kinesin-5 motor core. AB - Essential in mitosis, the human Kinesin-5 protein is a target for >80 classes of allosteric compounds that bind to a surface-exposed site formed by the L5 loop. Not established is why there are differing efficacies in drug inhibition. Here we compare the ligand-bound states of two L5-directed inhibitors against 15 Kinesin 5 mutants by ATPase assays and IR spectroscopy. Biochemical kinetics uncovers functional differences between individual residues at the N or C termini of the L5 loop. Infrared evaluation of solution structures and multivariate analysis of the vibrational spectra reveal that mutation and/or ligand binding not only can remodel the allosteric binding surface but also can transmit long range effects. Changes in L5-localized 3(10) helix and disordered content, regardless of substitution or drug potency, are experimentally detected. Principal component analysis couples these local structural events to two types of rearrangements in beta-sheet hydrogen bonding. These transformations in beta-sheet contacts are correlated with inhibitory drug response and are corroborated by wild type Kinesin-5 crystal structures. Despite considerable evolutionary divergence, our data directly support a theorized conserved element for long distance mechanochemical coupling in kinesin, myosin, and F(1)-ATPase. These findings also suggest that these relatively rapid IR approaches can provide structural biomarkers for clinical determination of drug sensitivity and drug efficacy in nucleotide triphosphatases. PMID- 20299461 TI - A novel function of sphingosine kinase 1 suppression of JNK activity in preventing inflammation and injury. AB - The mechanism underlying the protective effect of sphingosine kinase 1 (SphK1) in inflammatory injury is not clear. We demonstrated using SphK1-null mice (SphK1(-/ )) the crucial role of SphK1 in suppressing lipopolysaccharide-induced neutrophil oxidant production and sequestration in lungs and mitigating lung inflammatory injury. This effect of SphK1 was independent of the production of sphingosine 1 phosphate, the product of SphK1 activity. The anti-inflammatory effect of SphK1 in the lipopolysaccharide model was mediated through SphK1 interaction with JNK. SphK1 stabilization of JNK in turn inhibited JNK binding to the JNK-interacting protein 3 (JIP3) and thus abrogated the activation of NADPH oxidase and oxidant generation and resultant NF-kappaB activation. Therefore, SphK1-mediated down regulation of JNK activity serves to dampen inflammation and tissue injury. PMID- 20299462 TI - Angiotensin II stimulates thick ascending limb NO production via AT(2) receptors and Akt1-dependent nitric-oxide synthase 3 (NOS3) activation. AB - Angiotensin II (Ang II) acutely stimulates thick ascending limb (TAL) NO via an unknown mechanism. In endothelial cells, activation of Ang II type 2 receptor (AT(2)) stimulates NO. Akt1 activates NOS3 by direct phosphorylation. We hypothesized that Ang II stimulates TAL NO production via AT(2)-mediated Akt1 activation, which phosphorylates NOS3 at serine 1177. We measured NO production by fluorescence microscopy. In isolated TALs, Ang II (100 nm) increased NO production by 1.1 +/- 0.2 fluorescence units/min (p < 0.01). Ang II increased cGMP accumulation by 4.9 +/- 1.3 fmol/microg (p < 0.01). Upon adding the AT(2) antagonist PD123319 (1 microm), Ang II failed to stimulate NO (0.1 +/- 0.1 fluorescence units/min; p < 0.001 versus Ang II); adding the AT(1) antagonist losartan (1 microm) resulted in Ang II stimulating NO by 0.9 +/- 0.1 fluorescence units/min. Akt inhibitor (5 microm) blocked Ang II-stimulated NO (-0.1 +/- 0.2 fluorescence units/min versus inhibitor alone). Phospho-Akt1 increased by 72% after 5 min (p < 0.006), returning to basal after 10 min. Phospho-Akt2 did not change after 5 min but increased by 115 and 163% after 10 and 15 min (p < 0.02). Phospho-Akt3 did not change. An AT(2) agonist increased pAkt1 by 78% (p < 0.02), PI3K inhibition blocked this effect. In TALs transduced with dominant negative Akt1, Ang II failed to stimulate NO (0.1 +/- 0.2 fluorescence units/min versus 1.2 +/- 0.2 for controls; p < 0.001). Ang II increased phospho-NOS3 at serine 1177 by 130% (p < 0.01) and 150% after 5 and 10 min (p < 0.02). Ang II increased phosphoNOS3 at serine 633 by 50% after 5 min (p < 0.01). Akt inhibition prevented NOS3 phosphorylation. We concluded that Ang II enhances TAL NO production via activation of AT(2) and Akt1-dependent phosphorylation of NOS3 at serines 1177 and 633. PMID- 20299463 TI - A combined computational and functional approach identifies new residues involved in pH-dependent gating of ASIC1a. AB - Acid-sensing ion channels (ASICs) are key receptors for extracellular protons. These neuronal nonvoltage-gated Na(+) channels are involved in learning, the expression of fear, neurodegeneration after ischemia, and pain sensation. We have applied a systematic approach to identify potential pH sensors in ASIC1a and to elucidate the mechanisms by which pH variations govern ASIC gating. We first calculated the pK(a) value of all extracellular His, Glu, and Asp residues using a Poisson-Boltzmann continuum approach, based on the ASIC three-dimensional structure, to identify candidate pH-sensing residues. The role of these residues was then assessed by site-directed mutagenesis and chemical modification, combined with functional analysis. The localization of putative pH-sensing residues suggests that pH changes control ASIC gating by protonation/deprotonation of many residues per subunit in different channel domains. Analysis of the function of residues in the palm domain close to the central vertical axis of the channel allowed for prediction of conformational changes of this region during gating. Our study provides a basis for the intrinsic ASIC pH dependence and describes an approach that can also be applied to the investigation of the mechanisms of the pH dependence of other proteins. PMID- 20299464 TI - Alterations in skeletal muscle fatty acid handling predisposes middle-aged mice to diet-induced insulin resistance. AB - OBJECTIVE: Although advanced age is a risk factor for type 2 diabetes, a clear understanding of the changes that occur during middle age that contribute to the development of skeletal muscle insulin resistance is currently lacking. Therefore, we sought to investigate how middle age impacts skeletal muscle fatty acid handling and to determine how this contributes to the development of diet induced insulin resistance. RESEARCH DESIGN AND METHODS: Whole-body and skeletal muscle insulin resistance were studied in young and middle-aged wild-type and CD36 knockout (KO) mice fed either a standard or a high-fat diet for 12 weeks. Molecular signaling pathways, intramuscular triglycerides accumulation, and targeted metabolomics of in vivo mitochondrial substrate flux were also analyzed in the skeletal muscle of mice of all ages. RESULTS: Middle-aged mice fed a standard diet demonstrated an increase in intramuscular triglycerides without a concomitant increase in insulin resistance. However, middle-aged mice fed a high fat diet were more susceptible to the development of insulin resistance-a condition that could be prevented by limiting skeletal muscle fatty acid transport and excessive lipid accumulation in middle-aged CD36 KO mice. CONCLUSION: Our data provide insight into the mechanisms by which aging becomes a risk factor for the development of insulin resistance. Our data also demonstrate that limiting skeletal muscle fatty acid transport is an effective approach for delaying the development of age-associated insulin resistance and metabolic disease during exposure to a high-fat diet. PMID- 20299465 TI - Prevention of diabetes by FTY720-mediated stabilization of peri-islet tertiary lymphoid organs. AB - OBJECTIVE: The nonobese diabetic (NOD) mouse is a well-established mouse model of spontaneous type 1 diabetes, which is characterized by an autoimmune destruction of the insulin-secreting pancreatic beta-cells. In this study, we address the role of tertiary lymphoid organs (TLOs) that form in the pancreas of NOD mice during disease progression. METHODS: We developed a model designed to "lock" lymphocytes in the pancreatic lymph node (PLN) and pancreas by the use of FTY720, which blocks the exit of lymphocytes from lymph nodes. A combination of flow cytometry, immunofluorescence, and analysis of clinical scores was used to study the effects of long-term FTY720 treatment on TLO development and development of diabetes. RESULTS: Continuous treatment of NOD mice with FTY720 prevented diabetes development even at a time of significant insulitis. Treatment withdrawal led to accelerated disease independent of the PLN. Interestingly, naive T-cells trafficked to and proliferated in the TLOs. In addition, morphological changes were observed that occurred during the development of the disease. Remarkably, although the infiltrates are not organized into T/B-cell compartments in 8-week-old mice, by 20 weeks of age, and in age-matched mice undergoing FTY720 treatment, the infiltrates showed a high degree of organization. However, in naturally and FTY720-induced diabetic mice, T/B-cell compartmentalization was lost. CONCLUSION: Our data show that TLOs are established during diabetes development and suggest that islet destruction is due to a loss of TLO integrity, which may be prevented by FTY720 treatment. PMID- 20299466 TI - Mechanisms of insulin resistance after insulin-induced hypoglycemia in humans: the role of lipolysis. AB - OBJECTIVE: Changes in glucose metabolism occurring during counterregulation are, in part, mediated by increased plasma free fatty acids (FFAs), as a result of hypoglycemia-activated lipolysis. However, it is not known whether FFA plays a role in the development of posthypoglycemic insulin resistance as well. RESEARCH DESIGN AND METHODS: We conducted a series of studies in eight healthy volunteers using acipimox, an inhibitor of lipolysis. Insulin action was measured during a 2 h hyperinsulinemic-euglycemic clamp (plasma glucose [PG] 5.1 mmo/l) from 5:00 p.m. to 7:00 p.m. or after a 3-h morning hyperinsulinemic-glucose clamp (from 10 a.m. to 1:00 p.m.), either euglycemic (study 1) or hypoglycemic (PG 3.2 mmol/l, studies 2-4), during which FFA levels were allowed to increase (study 2), were suppressed by acipimox (study 3), or were replaced by infusing lipids (study 4). [6,6-(2)H(2)]-Glucose was infused to measure glucose fluxes. RESULTS: Plasma adrenaline, norepinephrine, growth hormone, and cortisol levels were unchanged (P > 0.2). Glucose infusion rates (GIRs) during the euglycemic clamp were reduced by morning hypoglycemia in study 2 versus study 1 (16.8 +/- 2.3 vs. 34.1 +/- 2.2 micromol/kg/min, respectively, P < 0.001). The effect was largely removed by blockade of lipolysis during hypoglycemia in study 3 (28.9 +/- 2.6 micromol/kg/min, P > 0.2 vs. study 1) and largely reproduced by replacement of FFA in study 4 (22.3 +/- 2.8 micromol/kg/min, P < 0.03 vs. study 1). Compared with study 2, blockade of lipolysis in study 3 decreased endogenous glucose production (2 +/- 0.3 vs. 0.85 +/- 0.1 micromol/kg/min, P < 0.05) and increased glucose utilization (16.9 +/- 1.85 vs. 28.5 +/- 2.7 micromol/kg/min, P < 0.05). In study 4, GIR fell by approximately 23% (22.3 +/- 2.8 micromol/kg/min, vs. study 3, P = 0.058), indicating a role of acipimox per se on insulin action. CONCLUSION: Lipolysis induced by hypoglycemia counterregulation largely mediates posthypoglycemic insulin resistance in healthy subjects, with an estimated overall contribution of approximately 39%. PMID- 20299467 TI - Ectopic expression of E2F1 stimulates beta-cell proliferation and function. AB - OBJECTIVE: Generating functional beta-cells by inducing their proliferation may provide new perspectives for cell therapy in diabetes. Transcription factor E2F1 controls G(1)- to S-phase transition during the cycling of many cell types and is required for pancreatic beta-cell growth and function. However, the consequences of overexpression of E2F1 in beta-cells are unknown. RESEARCH DESIGN AND METHODS: The effects of E2F1 overexpression on beta-cell proliferation and function were analyzed in isolated rat beta-cells and in transgenic mice. RESULTS: Adenovirus AdE2F1-mediated overexpression of E2F1 increased the proliferation of isolated primary rat beta-cells 20-fold but also enhanced beta-cell death. Coinfection with adenovirus AdAkt expressing a constitutively active form of Akt (protein kinase B) suppressed beta-cell death to control levels. At 48 h after infection, the total beta-cell number and insulin content were, respectively, 46 and 79% higher in AdE2F1+AdAkt-infected cultures compared with untreated. Conditional overexpression of E2F1 in mice resulted in a twofold increase of beta-cell proliferation and a 70% increase of pancreatic insulin content, but did not increase beta-cell mass. Glucose-challenged insulin release was increased, and the mice showed protection against toxin-induced diabetes. CONCLUSIONS: Overexpression of E2F1, either in vitro or in vivo, can stimulate beta-cell proliferation activity. In vivo E2F1 expression significantly increases the insulin content and function of adult beta-cells, making it a strategic target for therapeutic manipulation of beta-cell function. PMID- 20299469 TI - Idd9.2 and Idd9.3 protective alleles function in CD4+ T-cells and nonlymphoid cells to prevent expansion of pathogenic islet-specific CD8+ T-cells. AB - OBJECTIVE: Multiple type 1 diabetes susceptibility genes have now been identified in both humans and mice, yet mechanistic understanding of how they impact disease pathogenesis is still minimal. We have sought to dissect the cellular basis for how the highly protective mouse Idd9 region limits the expansion of autoreactive CD8(+) T-cells, a key cell type in destruction of the islets. RESEARCH DESIGN AND METHODS: We assess the endogenous CD8(+) T-cell repertoire for reactivity to the islet antigen glucose-6-phosphatase-related protein (IGRP). Through the use of adoptively transferred T-cells, bone marrow chimeras, and reconstituted severe combined immunodeficient mice, we identify the protective cell types involved. RESULTS: IGRP-specific CD8(+) T-cells are present at low frequency in the insulitic lesions of Idd9 mice and could not be recalled in the periphery by viral expansion. We show that Idd9 genes act extrinsically to the CD8(+) T-cell to prevent the massive expansion of pathogenic effectors near the time of disease onset that occurs in NOD mice. The subregions Idd9.2 and Idd9.3 mediated this effect. Interestingly, the Idd9.1 region, which provides significant protection from disease, did not prevent the expansion of autoreactive CD8(+) T-cells. Expression of Idd9 genes was required by both CD4(+) T-cells and a nonlymphoid cell to induce optimal tolerance. CONCLUSIONS: Idd9 protective alleles are associated with reduced expansion of IGRP-specific CD8(+) T-cells. Intrinsic expression of protective Idd9 alleles in CD4(+) T-cells and nonlymphoid cells is required to achieve an optimal level of tolerance. Protective alleles in the Idd9.2 congenic subregion are required for the maximal reduction of islet specific CD8(+) T-cells. PMID- 20299468 TI - Influence of insulin in the ventromedial hypothalamus on pancreatic glucagon secretion in vivo. AB - OBJECTIVE: Insulin released by the beta-cell is thought to act locally to regulate glucagon secretion. The possibility that insulin might also act centrally to modulate islet glucagon secretion has received little attention. RESEARCH DESIGN AND METHODS: Initially the counterregulatory response to identical hypoglycemia was compared during intravenous insulin and phloridzin infusion in awake chronically catheterized nondiabetic rats. To explore whether the disparate glucagon responses seen were in part due to changes in ventromedial hypothalamus (VMH) exposure to insulin, bilateral guide cannulas were inserted to the level of the VMH and 8 days later rats received a VMH microinjection of either 1) anti-insulin affibody, 2) control affibody, 3) artificial extracellular fluid, 4) insulin (50 microU), 5) insulin receptor antagonist (S961), or 6) anti insulin affibody plus a gamma-aminobutyric acid A (GABA(A)) receptor agonist muscimol, prior to a hypoglycemic clamp or under baseline conditions. RESULTS: As expected, insulin-induced hypoglycemia produced a threefold increase in plasma glucagon. However, the glucagon response was fourfold to fivefold greater when circulating insulin did not increase, despite equivalent hypoglycemia and C peptide suppression. In contrast, epinephrine responses were not altered. The phloridzin-hypoglycemia induced glucagon increase was attenuated (40%) by VMH insulin microinjection. Conversely, local VMH blockade of insulin amplified glucagon twofold to threefold during insulin-induced hypoglycemia. Furthermore, local blockade of basal insulin levels or insulin receptors within the VMH caused an immediate twofold increase in fasting glucagon levels that was prevented by coinjection to the VMH of a GABA(A) receptor agonist. CONCLUSIONS: Together, these data suggest that insulin's inhibitory effect on alpha-cell glucagon release is in part mediated at the level of the VMH under both normoglycemic and hypoglycemic conditions. PMID- 20299470 TI - Extracellular fatty acid synthase: a possible surrogate biomarker of insulin resistance. AB - CONTEXT: Circulating fatty acid synthase (FASN) is a biomarker of metabolically demanding human diseases. The aim of this study was to determine whether circulating FASN could be a biomarker of overnutrition-induced metabolic stress and insulin resistance in common metabolic disorders. RESEARCH DESIGN AND METHODS: Circulating FASN was evaluated in two cross-sectional studies in association with insulin sensitivity and in four longitudinal studies investigating the effect of diet- and surgery-induced weight loss, physical training, and adipose tissue expansion using peroxisome proliferator-activated receptor agonist rosiglitazone on circulating FASN. RESULTS: Age- and BMI adjusted FASN concentrations were significantly increased in association with obesity-induced insulin resistance in two independent cohorts. Both visceral and subcutaneous FASN expression and protein levels correlated inversely with extracellular circulating FASN (P = -0.63; P < 0.0001), suggesting that circulating FASN is linked to depletion of intracellular FASN. Improved insulin sensitivity induced by therapeutic strategies that decreased fat mass (diet induced, surgery induced, or physical training) all led to decreased FASN levels in blood (P values between 0.02 and 0.04). To discriminate whether this was an effect related to insulin sensitization, we also investigated the effects of rosiglitazone. Rosiglitazone did not lead to significant changes in circulating FASN concentration. CONCLUSIONS: Our results suggest that circulating FASN is a biomarker of overnutrition-induced insulin resistance that could provide diagnostic and prognostic advantages by providing insights on the individualized metabolic stress. PMID- 20299471 TI - FTO genetic variation and association with obesity in West Africans and African Americans. AB - OBJECTIVE: The FTO gene is one of the most consistently replicated loci for obesity. However, data from populations of African ancestry are limited. We evaluated genetic variation in the FTO gene and investigated associations with obesity in West Africans and African Americans. RESEARCH DESIGN AND METHODS: The study samples comprised 968 African Americans (59% female, mean age 49 years, mean BMI 30.8 kg/m(2)) and 517 West Africans (58% female, mean age 54 years, mean BMI 25.5 kg/m(2)). FTO genetic variation was evaluated by genotyping 262 tag single nucleotide polymorphisms (SNPs) across the entire gene. Association of each SNP with BMI, waist circumference, and percent fat mass was investigated under an additive model. RESULTS: As expected, both African-ancestry samples showed weaker linkage disequilibrium (LD) patterns compared with other continental (e.g., European) populations. Several intron 8 SNPs, in addition to intron 1 SNPs, showed significant associations in both study samples. The combined effect size for BMI for the top SNPs from meta-analysis was 0.77 kg/m(2) (P = 0.009, rs9932411) and 0.70 kg/m(2) (P = 0.006, rs7191513). Two previously reported associations with intron 1 SNPs (rs1121980 and rs7204609, r(2) = 0.001) were replicated among the West Africans. CONCLUSIONS: The FTO gene shows significant differences in allele frequency and LD patterns in populations of African ancestry compared with other continental populations. Despite these differences, we observed evidence of associations with obesity in African Americans and West Africans, as well as evidence of heterogeneity in association. More studies of FTO in multiple ethnic groups are needed. PMID- 20299472 TI - Activation of AMP-activated protein kinase inhibits oxidized LDL-triggered endoplasmic reticulum stress in vivo. AB - OBJECTIVE: The oxidation of LDLs is considered a key step in the development of atherosclerosis. How LDL oxidation contributes to atherosclerosis remains poorly defined. Here we report that oxidized and glycated LDL (HOG-LDL) causes aberrant endoplasmic reticulum (ER) stress and that the AMP-activated protein kinase (AMPK) suppressed HOG-LDL-triggered ER stress in vivo. RESEARCH DESIGN AND METHODS: ER stress markers, sarcoplasmic/endoplasmic reticulum Ca(2+) ATPase (SERCA) activity and oxidation, and AMPK activity were monitored in cultured bovine aortic endothelial cells (BAECs) exposed to HOG-LDL or in isolated aortae from mice fed an atherogenic diet. RESULTS: Exposure of BAECs to clinically relevant concentrations of HOG-LDL induced prolonged ER stress and reduced SERCA activity but increased SERCA oxidation. Chronic administration of Tempol (a potent antioxidant) attenuated both SERCA oxidation and aberrant ER stress in mice fed a high-fat diet in vivo. Likewise, AMPK activation by pharmacological (5'-aminoimidazole-4-carboxymide-1-beta-d-ribofuranoside, metformin, and statin) or genetic means (adenoviral overexpression of constitutively active AMPK mutants) significantly mitigated ER stress and SERCA oxidation and improved the endothelium-dependent relaxation in isolated mouse aortae. Finally, Tempol administration markedly attenuated impaired endothelium-dependent vasorelaxation, SERCA oxidation, ER stress, and atherosclerosis in ApoE(-/-) and ApoE(-/ )/AMPKalpha2(-/-) fed a high-fat diet. CONCLUSION: We conclude that HOG-LDL, via enhanced SERCA oxidation, causes aberrant ER stress, endothelial dysfunction, and atherosclerosis in vivo, all of which are inhibited by AMPK activation. PMID- 20299473 TI - TBC1D1 regulates insulin- and contraction-induced glucose transport in mouse skeletal muscle. AB - OBJECTIVE: TBC1D1 is a member of the TBC1 Rab-GTPase family of proteins and is highly expressed in skeletal muscle. Insulin and contraction increase TBC1D1 phosphorylation on phospho-Akt substrate motifs (PASs), but the function of TBC1D1 in muscle is not known. Genetic linkage analyses show a TBC1D1 R125W missense variant confers risk for severe obesity in humans. The objective of this study was to determine whether TBC1D1 regulates glucose transport in skeletal muscle. RESEARCH DESIGN AND METHODS: In vivo gene injection and electroporation were used to overexpress wild-type and several mutant TBC1D1 proteins in mouse tibialis anterior muscles, and glucose transport was measured in vivo. RESULTS: Expression of the obesity-associated R125W mutant significantly decreased insulin stimulated glucose transport in the absence of changes in TBC1D1 PAS phosphorylation. Simultaneous expression of an inactive Rab-GTPase (GAP) domain of TBC1D1 in the R125W mutant reversed this decrease in glucose transport caused by the R125W mutant. Surprisingly, expression of TBC1D1 mutated to Ala on four conserved Akt and/or AMP-activated protein kinase predicted phosphorylation sites (4P) had no effect on insulin-stimulated glucose transport. In contrast, expression of the TBC1D1 4P mutant decreased contraction-stimulated glucose transport, an effect prevented by concomitant disruption of TBC1D1 Rab-GAP activity. There was no effect of the R125W mutation on contraction-stimulated glucose transport. CONCLUSIONS: TBC1D1 regulates both insulin- and contraction stimulated glucose transport, and this occurs via distinct mechanisms. The R125W mutation of TBC1D1 impairs skeletal muscle glucose transport, which could be a mechanism for the obesity associated with this mutation. PMID- 20299474 TI - Inhibition of connective tissue growth factor overexpression in diabetic retinopathy by SERPINA3K via blocking the WNT/beta-catenin pathway. AB - OBJECTIVE: Connective tissue growth factor (CTGF) is a major fibrogenic factor. Increased retinal CTGF levels have been implicated to play a role in diabetic retinopathy. SERPINA3K is a serine proteinase inhibitor, and its levels were decreased in retinas with diabetic retinopathy. The purpose of this study was to investigate the role of SERPINA3K in the regulation of CTGF and fibrogenesis and its mechanism of action. RESEARCH DESIGN AND METHODS: Adenovirus expressing SERPINA3K was injected intravitreally into streptozotocin-induced diabetic rats. CTGF expression was measured using Western blot analysis and real-time RT-PCR. Fibrosis was evaluated by quantifying retinal fibronectin using enzyme-linked immunosorbent assay. Wnt pathway activation was determined by phosphorylation of LDL receptor-related protein 6, a coreceptor of Wnt ligands, and stabilization of beta-catenin, an essential effector of the canonical Wnt pathway. RESULTS: Ad SERPINA3K attenuated the CTGF and fibronectin overexpression in retinas of diabetic rats. In cultured retinal cells, SERPINA3K blocked the overproduction of CTGF induced by high glucose. Dickkopf-1, a specific Wnt antagonist, also attenuated the high-glucose-induced CTGF overexpression, indicating a role of Wnt signaling in CTGF overexpression in diabetes. Similarly, increased SERPINA3K blocked Wnt pathway activation in diabetic retinas and in cells treated with high glucose. Further, SERPINA3K also attenuated the Wnt3a-induced activation of the canonical Wnt pathway and the overexpression of CTGF. CONCLUSION: SERPINA3K is an antifibrogenic factor, and its antifibrogenic activity is through blocking the Wnt pathway. Decreased SERPINA3K levels may contribute to the fibrosis in diabetic retinopathy. PMID- 20299475 TI - Chronic rapamycin treatment causes glucose intolerance and hyperlipidemia by upregulating hepatic gluconeogenesis and impairing lipid deposition in adipose tissue. AB - OBJECTIVE: The mammalian target of rapamycin (mTOR)/p70 S6 kinase 1 (S6K1) pathway is a critical signaling component in the development of obesity-linked insulin resistance and operates a nutrient-sensing negative feedback loop toward the phosphatidylinositol 3-kinase (PI 3-kinase)/Akt pathway. Whereas acute treatment of insulin target cells with the mTOR complex 1 (mTORC1) inhibitor rapamycin prevents nutrient-induced insulin resistance, the chronic effect of rapamycin on insulin sensitivity and glucose metabolism in vivo remains elusive. RESEARCH DESIGN AND METHODS: To assess the metabolic effects of chronic inhibition of the mTORC1/S6K1 pathway, rats were treated with rapamycin (2 mg/kg/day) or vehicle for 15 days before metabolic phenotyping. RESULTS: Chronic rapamycin treatment reduced adiposity and fat cell number, which was associated with a coordinated downregulation of genes involved in both lipid uptake and output. Rapamycin treatment also promoted insulin resistance, severe glucose intolerance, and increased gluconeogenesis. The latter was associated with elevated expression of hepatic gluconeogenic master genes, PEPCK and G6Pase, and increased expression of the transcriptional coactivator peroxisome proliferator activated receptor-gamma coactivator-1alpha (PGC-1alpha) as well as enhanced nuclear recruitment of FoxO1, CRTC2, and CREB. These changes were observed despite normal activation of the insulin receptor substrate/PI 3-kinase/Akt axis in liver of rapamycin-treated rats, as expected from the blockade of the mTORC1/S6K1 negative feedback loop. CONCLUSIONS: These findings unravel a novel mechanism by which mTORC1/S6K1 controls gluconeogenesis through modulation of several key transcriptional factors. The robust induction of the gluconeogenic program in liver of rapamycin-treated rats underlies the development of severe glucose intolerance even in the face of preserved hepatic insulin signaling to Akt and despite a modest reduction in adiposity. PMID- 20299476 TI - Naturally arising human CD4 T-cells that recognize islet autoantigens and secrete interleukin-10 regulate proinflammatory T-cell responses via linked suppression. AB - OBJECTIVE: Regulatory T-cells (Tregs) recognizing islet autoantigens are proposed as a key mechanism in the maintenance of self-tolerance and protection from type 1 diabetes. To date, however, detailed information on such cells in humans, and insight into their mechanisms of action, has been lacking. We previously reported that a subset of CD4 T-cells secreting high levels of the immunosuppressive cytokine interleukin-10 (IL-10) is significantly associated with late onset of type 1 diabetes and is constitutively present in a majority of nondiabetic individuals. Here, we test the hypothesis that these T-cells represent a naturally generated population of Tregs capable of suppressing proinflammatory T cell responses. RESEARCH DESIGN AND METHODS: We isolated and cloned islet specific IL-10-secreting CD4(+) T-cells from nondiabetic individuals after brief ex vivo exposure to islet autoantigens using cytokine capture technology and examined their phenotype and regulatory potential. RESULTS: Islet-specific IL 10(+) CD4 T-cells are potent suppressors of Th1 effector cells, operating through a linked suppression mechanism in which there is an absolute requirement for the cognate antigen of both the regulatory and effector T-cells to be presented by the same antigen-presenting cell (APC). The regulatory T-cells secrete perforin and granzymes, and suppression is associated with the specific killing of APCs presenting antigen to effector T-cells. CONCLUSIONS: This hitherto undescribed population of islet autoantigen-specific Tregs displays unique characteristics that offer exquisite specificity and control over the potential for pathological autoreactivity and may provide a suitable target with which to strengthen beta cell-specific tolerance. PMID- 20299477 TI - Deletion of the alpha-arrestin protein Txnip in mice promotes adiposity and adipogenesis while preserving insulin sensitivity. AB - OBJECTIVE: Thioredoxin interacting protein (Txnip), a regulator of cellular oxidative stress, is induced by hyperglycemia and inhibits glucose uptake into fat and muscle, suggesting a role for Txnip in type 2 diabetes pathogenesis. Here, we tested the hypothesis that Txnip-null (knockout) mice are protected from insulin resistance induced by a high-fat diet. RESEARCH DESIGN AND METHODS: Txnip gene-deleted (knockout) mice and age-matched wild-type littermate control mice were maintained on a standard chow diet or subjected to 4 weeks of high-fat feeding. Mice were assessed for body composition, fat development, energy balance, and insulin responsiveness. Adipogenesis was measured from ex vivo fat preparations, and in mouse embryonic fibroblasts (MEFs) and 3T3-L1 preadipocytes after forced manipulation of Txnip expression. RESULTS: Txnip knockout mice gained significantly more adipose mass than controls due to a primary increase in both calorie consumption and adipogenesis. Despite increased fat mass, Txnip knockout mice were markedly more insulin sensitive than controls, and augmented glucose transport was identified in both adipose and skeletal muscle. RNA interference gene-silenced preadipocytes and Txnip(-/-) MEFs were markedly adipogenic, whereas Txnip overexpression impaired adipocyte differentiation. As increased adipogenesis and insulin sensitivity suggested aspects of augmented peroxisome proliferator-activated receptor-gamma (PPARgamma) response, we investigated Txnip's regulation of PPARgamma function; manipulation of Txnip expression directly regulated PPARgamma expression and activity. CONCLUSIONS: Txnip deletion promotes adiposity in the face of high-fat caloric excess; however, loss of this alpha-arrestin protein simultaneously enhances insulin responsiveness in fat and skeletal muscle, revealing Txnip as a novel mediator of insulin resistance and a regulator of adipogenesis. PMID- 20299478 TI - Critical role of the mesenteric depot versus other intra-abdominal adipose depots in the development of insulin resistance in young rats. AB - OBJECTIVE: Age-associated insulin resistance may be caused by increased visceral adiposity and older animals appear to be more susceptible to obesity-related resistance than young animals. However, it is unclear to what extent the portally drained mesenteric fat depot influences this susceptibility. RESEARCH DESIGN AND METHODS: Young high-fat-fed and old obese rats were subjected to 0, 2, 4, or 6 weeks of caloric restriction. Insulin sensitivity (S(I)) was assessed by hyperinsulinemic clamp and lean body mass (LBM) and total body fat were assessed by (18)O-water administration. RESULTS: Six weeks of caloric restriction caused a similar reduction in body weight in young and old animals (P = 0.748) that was not due to reduced subcutaneous fat or LBM, but rather preferential loss of abdominal fat (P < 0.05). Most notably, mesenteric fat was reduced equivalently in young and old rats after 6 weeks of caloric restriction ( approximately decrease 53%; P = 0.537). Despite similar visceral fat loss, S(I) improved less in old ( increase 32.76 +/- 9.80%) than in young ( increase 82.91 +/- 12.66%) rats versus week 0. In addition, there was significantly more reversal of fat accumulation in the liver in young (% reduction: 89 +/- 2) versus old (64 +/- 5) rats (P < 0.0001). Furthermore, in young rats, S(I) changed much more rapidly for a given change in mesenteric fat versus other abdominal depots (slope = 0.53 vs. < or =0.27 kg/min/mg per % fat). CONCLUSIONS Improved S(I) during caloric restriction correlated with a preferential abdominal fat loss. This improvement was refractory in older animals, likely because of slower liberation of hepatic lipid. Furthermore, mesenteric fat was a better predictor of S(I) than other abdominal depots in young but not old rats. These results suggest a singular role for mesenteric fat to determine insulin resistance. This role may be related to delivery of lipid to liver, and associated accumulation of liver fat. PMID- 20299479 TI - Alterations in retinal microvascular geometry in young type 1 diabetes. AB - OBJECTIVE: To describe retinal microvascular geometric parameters in young patients with type 1 diabetes. RESEARCH DESIGN AND METHODS: Patients with type 1 diabetes (aged 12-20 years) had clinical assessments and retinal photography following standardized protocol at a tertiary-care hospital in Sydney. Retinal microvascular geometry, including arteriolar and venular tortuosity, branching angles, optimality deviation, and length-to-diameter ratio (LDR), were measured from digitized photographs. Associations of these geometric characteristics with diabetes duration, A1C level, systolic blood pressure (SBP), and other risk factors were assessed. RESULTS: Of 1,159 patients enrolled, 944 (81.4%) had gradable photographs and 170 (14.7%) had retinopathy. Older age was associated with decreased arteriolar (P = 0.024) and venular (P = 0.002) tortuosity, and female subjects had larger arteriolar branching angle than male subjects (P = 0.03). After adjusting for age and sex, longer diabetes duration was associated with larger arteriolar branching angle (P 8.5 vs. or=40 prescriptions (>5 years) of metformin, based on 17 exposed case patients and 120 exposed control patients, was associated with an adjusted odds ratio of 0.44 (95% CI 0.24-0.82) for developing breast cancer compared with no use of metformin. Neither short-term metformin use nor use of sulfonylureas or other antidiabetes drugs was associated with a materially altered risk for breast cancer. CONCLUSIONS: A decreased risk of breast cancer was observed in female patients with type 2 diabetes using metformin on a long term basis. PMID- 20299481 TI - Online diabetes self-management program: a randomized study. AB - OBJECTIVE: We hypothesized that people with type 2 diabetes in an online diabetes self-management program, compared with usual-care control subjects, would 1) demonstrate reduced A1C at 6 and 18 months, 2) have fewer symptoms, 3) demonstrate increased exercise, and 4) have improved self-efficacy and patient activation. In addition, participants randomized to listserve reinforcement would have better 18-month outcomes than participants receiving no reinforcement. RESEARCH DESIGN AND METHODS: A total of 761 participants were randomized to 1) the program, 2) the program with e-mail reinforcement, or 3) were usual-care control subjects (no treatment). This sample included 110 American Indians/Alaska Natives (AI/ANs). Analyses of covariance models were used at the 6- and 18-month follow-up to compare groups. RESULTS: At 6 months, A1C, patient activation, and self-efficacy were improved for program participants compared with usual care control subjects (P < 0.05). There were no changes in other health or behavioral indicators. The AI/AN program participants demonstrated improvements in health distress and activity limitation compared with usual-care control subjects. The subgroup with initial A1C >7% demonstrated stronger improvement in A1C (P = 0.01). At 18 months, self-efficacy and patient activation were improved for program participants. A1C was not measured. Reinforcement showed no improvement. CONCLUSIONS: An online diabetes self-management program is acceptable for people with type 2 diabetes. Although the results were mixed they suggest 1) that the program may have beneficial effects in reducing A1C, 2) AI/AN populations can be engaged in and benefit from online interventions, and 3) our follow-up reinforcement appeared to have no value. PMID- 20299482 TI - Derivation and validation of a new cardiovascular risk score for people with type 2 diabetes: the new zealand diabetes cohort study. AB - OBJECTIVE: To derive a 5-year cardiovascular disease (CVD) risk equation from usual-care data that is appropriate for people with type 2 diabetes from a wide range of ethnic groups, variable glycemic control, and high rates of albuminuria in New Zealand. RESEARCH DESIGN AND METHODS: This prospective open-cohort study used primary-care data from 36,127 people with type 2 diabetes without previous CVD to derive a CVD equation using Cox proportional hazards regression models. Data from 12,626 people from a geographically different area were used for validation. Outcome measure was time to first fatal or nonfatal cardiovascular event, derived from national hospitalization and mortality records. Risk factors were age at diagnosis, diabetes duration, sex, systolic blood pressure, smoking status, total cholesterol-to-HDL ratio, ethnicity, glycated hemoglobin (A1C), and urine albumin-to-creatinine ratio. RESULTS: Baseline median age was 59 years, 51% were women, 55% were of non-European ethnicity, and 33% had micro- or macroalbuminuria. Median follow-up was 3.9 years (141,169 person-years), including 10,030 individuals followed for at least 5 years. At total of 6,479 first cardiovascular events occurred during follow-up. The 5-year observed risk was 20.8% (95% CI 20.3-21.3). Risk increased with each 1% A1C (adjusted hazard ratio 1.06 [95% CI 1.05-1.08]), when macroalbuminuria was present (2.04 [1.89 2.21]), and in Indo-Asians (1.29 [1.14-1.46]) and Maori (1.23 [1.14-1.32]) compared with Europeans. The derived risk equations performed well on the validation cohort compared with other risk equations. CONCLUSIONS: Renal function, ethnicity, and glycemic control contribute significantly to cardiovascular risk prediction. Population-appropriate risk equations can be derived from routinely collected data. PMID- 20299483 TI - Independent metabolic syndrome variants predict new-onset coronary artery disease. AB - OBJECTIVE: Any combination of metabolic abnormalities may constitute the metabolic syndrome (MetS), conferring coronary artery disease (CAD) risk, but the independent effect of different combinations on CAD onset remains unknown. RESEARCH DESIGN AND METHODS" Healthy adult siblings (n = 987) of premature CAD (<60 years) case subjects were followed for 9.8 +/- 3.8 years. Baseline MetS variables (insulin sensitivity index, waist circumference, systolic blood pressure, HDL cholesterol, and triglycerides) were recombined into five principal components (PC1-5), and risk factor-adjusted proportional hazards for CAD onset of median-dichotomized PCs were estimated. RESULTS: The significant hazard ratios were as follows: for PC1 (all abnormalities except blood pressure) 1.66 (P = 0.036), PC2 (high blood pressure levels, high HDL cholesterol) 1.71 (P = 0.016), and PC4 (low HDL cholesterol, high insulin sensitivity, low triglycerides) 2.0 (P = 0.001). Traditionally defined MetS had a hazard ratio of 1.32 (P = 0.18). CONCLUSIONS: Independent MetS variants identified by PC analysis may explain metabolic mechanisms that increase CAD risk better than the presence of traditional MetS. PMID- 20299484 TI - Progression of cerebral atrophy and white matter hyperintensities in patients with type 2 diabetes. AB - OBJECTIVE: Type 2 diabetes is associated with a moderate degree of cerebral atrophy and a higher white matter hyperintensity (WMH) volume. How these brain imaging abnormalities evolve over time is unknown. The present study aims to quantify cerebral atrophy and WMH progression over 4 years in type 2 diabetes. RESEARCH DESIGN AND METHODS: A total of 55 patients with type 2 diabetes and 28 age-, sex-, and IQ-matched control participants had two 1.5T magnetic resonance imaging scans with a 4-year interval. Volumetric measurements of total brain, peripheral cerebrospinal fluid (CSF), lateral ventricles, and WMH were performed with k-nearest neighbor-based probabilistic segmentation. All volumes were expressed as percentage of intracranial volume. Linear regression analyses, adjusted for age and sex, were performed to compare brain volumes between the groups and to identify determinants of volumetric change within the type 2 diabetic group. RESULTS: At baseline, patients with type 2 diabetes had a significantly smaller total brain volume and larger peripheral CSF volume than control participants. In both groups, all volumes showed a significant change over time. Patients with type 2 diabetes had a greater increase in lateral ventricular volume than control participants (mean adjusted between-group difference in change over time [95% CI]: 0.11% in 4 years [0.00 to 0.22], P = 0.047). CONCLUSIONS: The greater increase in lateral ventricular volume over time in patients with type 2 diabetes compared with control participants shows that type 2 diabetes is associated with a slow increase of cerebral atrophy over the course of years. PMID- 20299485 TI - Hyperglycemia-induced platelet activation in type 2 diabetes is resistant to aspirin but not to a nitric oxide-donating agent. AB - OBJECTIVE: Acute, short-term hyperglycemia enhances high shear stress-induced platelet activation in type 2 diabetes. Several observations suggest that platelets in type 2 diabetes are resistant to inhibition by aspirin. Our aim was to assess comparatively the effect of aspirin, a nitric oxide-donating agent (NCX 4016), their combination, or placebo on platelet activation induced by acute hyperglycemia in type 2 diabetes. RESEARCH DESIGN AND METHODS: In a double-blind, placebo-controlled, randomized trial, 40 type 2 diabetic patients were allocated to 100 mg aspirin once daily, 800 mg NCX 4016 b.i.d., both of them, or placebo for 15 days. On day 15, 1 h after the morning dose, a 4-h hyperglycemic clamp (plasma glucose 13.9 mmol/l) was performed, and blood samples were collected before and immediately after it for platelet activation and cyclooxygenase-1 (COX 1) inhibition studies. RESULTS Acute hyperglycemia enhanced shear stress-induced platelet activation in placebo-treated patients (basal closure time 63 +/- 7.1 s, after hyperglycemia 49.5 +/- 1.4 s, -13.5 +/- 6.3 s, P < 0.048). Pretreatment with aspirin, despite full inhibition of platelet COX-1, did not prevent it ( 12.7 +/- 6.9 s, NS vs. placebo). On the contrary, pretreatment with the NO donor NCX 4016, alone or in combination with aspirin, suppressed platelet activation induced by acute hyperglycemia (NCX 4016 +10.5 +/- 8.3 s; NCX 4016 plus aspirin: +12.0 +/- 10.7 s, P < 0.05 vs. placebo for both). Other parameters of shear stress-dependent platelet activation were also more inhibited by NCX 4016 than by aspirin, despite lesser inhibition of COX-1. CONCLUSIONS: Acute hyperglycemia induced enhancement of platelet activation is resistant to aspirin; a NO-donating agent suppresses it. Therapeutic approaches aiming at a wider platelet inhibitory action than that exerted by aspirin may prove useful in patients with type 2 diabetes. PMID- 20299486 TI - Transcription factor 7-like 2 (TCF7L2) polymorphism and hyperglycemia in an adult Italian population-based cohort. AB - OBJECTIVE: To assess whether TCF7L2 polymorphism has a role in the deterioration of glycemic control. RESEARCH DESIGN AND METHODS: Metabolic variables were evaluated at baseline and after 6-year follow-up in 1,480 Caucasian subjects from a population-based cohort. RESULTS: At baseline, T-allele carriers showed significantly lower BMI and homeostasis model assessment for beta-cell function (HOMA-B) values and higher fasting glycemia and diabetes prevalence. At follow up, fasting glucose and HOMA-B index were increased and reduced, respectively, in carriers of the T-allele. Incident impaired fasting glucose (IFG) and incident diabetes were 5.7, 10.7, 16.9% and 1.6, 1.7, 3.0% in the CC, CT, and TT genotypes, respectively. In a multiple logistic regression model, the association between incident IFG and the T-allele was significant (odds ratio [OR] 2.08 [95% CI 1.35-3.20] and 3.56 [2.11-5.98] in CT and TT genotypes, respectively). CONCLUSIONS: The T-allele of TCF7L2 rs7903146 polymorphism was independently associated with increasing fasting glucose values toward hyperglycemia in the follow-up. PMID- 20299487 TI - Validity of a single-factor model underlying the metabolic syndrome in children: a confirmatory factor analysis. AB - OBJECTIVE: We used confirmatory factor analysis to test whether a single factor might explain the clustering of the metabolic syndrome (MS) components in children. RESEARCH DESIGN AND METHODS: We studied 1,020 children aged 10-13 years from 20 schools in Cuenca, Spain. The single-factor model included: waist circumference (WC), fasting insulin, triglyceride to HDL cholesterol ratio (Triglyl/HDL-C), and mean arterial pressure (MAP). The standardized scores of the four variables in the model were used to develop a continuous MS index. RESULTS: Factor loadings were 0.67 for WC, 0.68 for fasting insulin, 0.57 for Triglyl/HDL C, and 0.37 for MAP. The single-factor model also showed a good fit to the data. As compared with Adult Treatment Panel III criteria, the MS index showed strong validity in the diagnosis of MS (area under the receiver operating characteristic curve = 0.98, 95% CI 0.96-0.99). CONCLUSIONS: A single underlying factor has acceptable validity to represent MS in children. PMID- 20299488 TI - Treatment of type 2 diabetes and outcomes in patients with heart failure: a nested case-control study from the U.K. General Practice Research Database. AB - OBJECTIVE: Diabetes and heart failure commonly coexist, and prior studies have suggested better outcomes with metformin than other antidiabetic agents. We designed this study to determine whether this association reflects a beneficial effect of metformin or a harmful effect of other agents. RESEARCH DESIGN AND METHODS: We performed a case-control study nested within the U.K. General Practice Research Database cohort in which diagnoses were assigned by each patient's primary care physician. Case subjects were patients 35 years or older, newly diagnosed with both heart failure and diabetes after January 1988, and who died prior to October 2007. Control subjects were matched to case subjects based on age, sex, clinic site, calendar year, and duration of follow-up. Analyses were adjusted for comorbidities, A1C, renal function, and BMI. RESULTS: The duration of concurrent diabetes and heart failure was 2.8 years (SD 2.6) in our 1,633 case subjects and 1,633 control subjects (mean age 78 years, 53% male). Compared with patients who were not exposed to antidiabetic drugs, the current use of metformin monotherapy (adjusted odds ratio 0.65 [0.48-0.87]) or metformin with or without other agents (0.72 [0.59-0.90]) was associated with lower mortality; however, use of other antidiabetic drugs or insulin was not associated with all-cause mortality. Conversely, the use of ACE inhibitors/angiotensin receptor blockers (0.55 [0.45-0.68]) and beta-blockers (0.76 [0.61-0.95]) were associated with reduced mortality. CONCLUSIONS: Our results confirm the benefits of trial-proven anti-failure therapies in patients with diabetes and support the use of metformin based strategies to lower glucose. PMID- 20299489 TI - MicroRNA-34a inhibits cell proliferation by repressing mitogen-activated protein kinase kinase 1 during megakaryocytic differentiation of K562 cells. AB - Phorbol 12-myristate 13-acetate (PMA) induces megakaryocytic differentiation of the human chronic myelocytic leukemia cell line K562. We examined the potential regulatory role of microRNAs (miRNAs) in this process. Genome-wide expression profiling identified 21 miRNAs (miRs) that were induced by the treatment of K562 cells with PMA. Among them, the expression of miR-34a, miR-221, and miR-222 was induced in the early stages and maintained throughout the late stages of differentiation. Cell signaling analysis showed that the activation of extracellular signal-regulated protein kinase (ERK) in response to PMA strongly induced miR-34a expression by transactivation via the activator protein-1 binding site in the upstream region of the miR-34a gene. Reporter gene assays identified mitogen-activated protein kinase kinase 1 (MEK1) as a direct target of miR-34a and c-fos as a direct target of miR-221/222. Although overexpression of the three miRNAs had little effect on cell differentiation, overexpression of miR-34a significantly repressed the proliferation of K562 cells with a concomitant reduction in MEK1 protein expression. Conversely, a locked nucleic acid probe against miR-34a significantly enhanced the proliferation of PMA-treated K562 cells. Taken together, the results show that PMA activates the MEK-ERK pathway and strongly induces miRNA-34a expression, which in turn inhibits cell proliferation by repressing the expression of MEK1. Thus, the results highlight an important regulatory role for miR-34a in the process of megakaryocytic differentiation, especially in the arrest of cell growth, which is a prerequisite for cells to enter differentiation. PMID- 20299490 TI - Secretagogue type, sex-steroid milieu, and abdominal visceral adiposity individually determine secretagogue-stimulated cortisol secretion. AB - DESIGN: While androgens and estrogens control glucocorticoid secretion in animal models, how the sex-steroid milieu determines cortisol secretion in humans is less clear. To address this issue, cortisol was measured in archival sera obtained at 10-min intervals for 5 h in 42 healthy men administered double placebo, placebo and testosterone, testosterone and dutasteride (to block 5alpha reductases type I and type II), or testosterone and anastrozole (to block aromatase) in a double-blind, placebo-controlled, prospectively randomized design. METHODS: Subjects received i.v. injection of saline, GHRH, GH-releasing peptide-2 (GHRP-2), somatostatin (SS), and GHRP-2/GHRH/l-arginine (triple stimulus) each on separate mornings fasting. Outcomes comprised cortisol concentrations, pulsatile cortisol secretion, and relationships with age or abdominal visceral fat (AVF). RESULTS: By ANCOVA, baseline (saline-infused) cortisol concentrations (nmol/l) did not differ among the sex-steroid milieus (overall mean 364+/-14). In contrast, stimulated peak cortisol concentrations were strongly determined by secretagogue type (P<0.001) as follows: triple stimulus (868+/-27)>GHRP-2 (616+/-42)>saline=SS=GHRH (grand mean 420+/-21). After GHRP-2 injection, pulsatile cortisol secretion increased with age (R(2)=0.16, P=0.012). After the triple stimulus, pulsatile cortisol secretion correlated i) inversely with serum 5alpha-dihydrotestosterone (DHT) concentrations (R(2)=0.53, P=0.026) and ii) directly with computerized tomography-estimated AVF (R(2)=0.11, P=0.038). CONCLUSION: Age, DHT concentrations, AVF, and secretagogue type influence pulsatile cortisol secretion at least in men. Further studies should be performed to assess ACTH secretion and native ghrelin action in defined sex steroid milieus. PMID- 20299491 TI - Complex relationship between free thyroxine and TSH in the regulation of thyroid function. AB - OBJECTIVE: The present study re-evaluates the inverse log TSH-free thyroxine (fT(4)) relationship, which has generally been assumed to characterize the thyroid pituitary hypothalamic feedback regulation in thyroid function. DESIGN AND METHODS: The correlation between fT(4) and TSH was analyzed in two data sets from differing time periods involving 3223 and 6605 patients referred for thyroid testing, representing the whole range of thyroid functions from hypothyroidism to hyperthyroidism. RESULTS: We found that the data do not support a linear log TSH fT(4) relationship; instead, the correlation's gradient varies with thyroid function. As a consequence, an alternate model, based on the error function, was introduced. When directly comparing the models by means of curve fitting, using F test and Akaike criteria, the alternate model results in a significantly better fit. The model was verified in the independent second set of data. Subgroup analysis of untreated patients added further proof to the non-linear model. CONCLUSIONS: We propose a refined non-linear model to describe the relationship between TSH and fT(4). It implies that TSH response to a deviating fT(4) value may not be log-linear, but may be disproportionally related to the extent of the deviation from an optimum set point. A better understanding of the complex nature of the TSH-fT(4) relationship may further the development of more precise clinical models and aid in better defining subclinical states of thyroid dysfunction. Also, it may encourage other biological interrelations to be reconsidered in the wake of advanced measurement techniques and more powerful computerized statistical procedures. PMID- 20299493 TI - The contribution of health plans and provider organizations to variations in measured plan quality. AB - OBJECTIVE: Some argue that health plans have minimal impacts on quality of care and that quality data collection should focus only on physician organizations. We investigate the relative impact of physician organizations and health plans on quality measures. DESIGN: Statistical analysis of data on 9 Healthcare Effectiveness Data and Information Set (HEDIS) measures from 6 health plans and 159 provider organizations. We use regression analyses to examine the amount of variation in HEDIS measures accounted for by variation across provider organizations, and whether accounting for health plans explains additional variation. We also examine whether accounting for provider organizations explains away variation in HEDIS scores across health plans. SETTING: Six health plans and 159 contracted provider groups in California. MAIN OUTCOME MEASURES: Nine HEDIS scores. RESULTS: For all nine measures studied, variation across provider organizations explains much of the HEDIS score variation. But, after accounting for variation across providers, variation across plans statistically significantly explains additional variation. We also find statistically significant differences across health plans in HEDIS rates that are not substantially affected when we control for the provider organization that cared for the patient. CONCLUSIONS: On their face, these results suggest that plans can influence quality independent of the selection of physician organizations with which they contract, in contrast to hypotheses that plans are 'too far' from patients to have an influence. Continued attention to collecting plan-level data is warranted. Further work should address other possible sources of variations in HEDIS scores, such as variability in plan administrative databases. PMID- 20299494 TI - Effectiveness and safety of colistin: prospective comparative cohort study. AB - BACKGROUND: Colistin has re-entered clinical use by necessity. We aimed to assess its effectiveness and safety compared with newer antibiotics. METHODS: This was a single-centre, prospective cohort study. Inclusion criteria were microbiologically documented pneumonia, urinary tract infection, surgical site infection, meningitis or bacteraemia treated appropriately with colistin versus imipenem, meropenem or ampicillin/sulbactam (comparators). All consecutive patients were included, only once, between May 2006 and July 2009. The primary outcome was 30 day mortality. Multivariable and Cox regression survival analyses were used to adjust comparisons between groups. Odds ratios (ORs) or hazard ratios (HRs) with 95% confidence intervals are reported. RESULTS: Two hundred patients treated with colistin and 295 patients treated with comparators were included. Treatment with colistin was associated with older age, admission from healthcare facilities, mechanical ventilation and lower rate of early appropriate antibiotic treatment. The 30 day mortality was 39% (78/200) for colistin versus 28.8% (85/295) for comparators; unadjusted OR 1.58 (1.08-2.31). In the adjusted analysis the OR was 1.44 (0.91-2.26) overall and 1.99 (1.06-3.77) for bacteraemic patients (n = 220). At the end of follow-up, treatment with colistin was significantly associated with cumulative mortality; adjusted HR 1.27 (1.01-1.60) overall and 1.65 (1.18-2.31) among patients with bacteraemia. Nephrotoxicity at the end of treatment was more frequent with colistin; OR adjusted for other risk factors for nephrotoxicity 3.31 (1.54-7.08). Treatment with colistin was followed by increased incidence of Proteus spp. infections during a 3 month follow-up. CONCLUSIONS: The need for colistin treatment is associated with poorer survival. Adjusted analyses suggest that colistin is less effective and more toxic than beta-lactam antibiotics. PMID- 20299492 TI - Retinal very long-chain PUFAs: new insights from studies on ELOVL4 protein. AB - Compared with other mammalian tissues, retina is highly enriched in PUFA. Long chain PUFA (LC-PUFA; C18-C24) are essential FAs that are enriched in the retina and are necessary for maintenance of normal retinal development and function. The retina, brain, and sperm also contain very LC-PUFA (VLC-PUFA; >C24). Although VLC PUFA were discovered more than two decades ago, very little is known about their biosynthesis and functional roles in the retina. This is due mainly to intrinsic difficulties associated with working on these unusually long polyunsaturated hydrocarbon chains and their existence in small amounts. Recent studies on the FA elongase elongation of very long chain fatty acids-4 (ELOVL4) protein, however, suggest that VLC-PUFA probably play some uniquely important roles in the retina as well as the other tissues. Mutations in the ELOVL4 gene are found in patients with autosomal dominant Stargardt disease. Here, we review the recent literature on VLC-PUFA with special emphasis on the elongases responsible for their synthesis. We focus on a novel elongase, ELOVL4, involved in the synthesis of VLC PUFA, and the importance of these FAs in maintaining the structural and functional integrity of retinal photoreceptors. PMID- 20299495 TI - Inhibition of Japanese encephalitis virus replication in cultured cells and mice by a peptide-conjugated morpholino oligomer. AB - BACKGROUND: Japanese encephalitis virus (JEV) has a significant impact on public health throughout Asia, and there is a pressing need for development of new therapeutics against it. METHODS: Peptide-conjugated phosphorodiamidate morpholino oligomers (PPMOs) are antisense agents that enter cells readily and interfere with gene expression. Four PPMOs, targeting various locations in the JEV genome, were evaluated for antiviral activity against JEV in cultured cells and the mouse model of JEV infection. RESULTS: A PPMO (P10882) targeting the JEV 3' cyclization sequence (3'CSI) had significant antiviral activity in Vero (epithelial), Neuro2A (neuronal) and J774E (macrophage) cells at concentrations that were not cytotoxic. P10882 added before infection suppressed JEV replication to an undetectable level in Vero cells and produced a 93% and 66% reduction in titre in J774E and Neuro2A cells, respectively, when measured at 24 h post infection. In uninfected cells, fluorescein-labelled PPMOs entered J774E cells most efficiently, followed by Vero and Neuro2A cells. The antiviral effect of P10882 was also demonstrated in vivo, where 60%-80% of 1-week-old mice treated intracerebrally with a 20 mg/kg dose of P10882 every 12 h for 5 days were protected from a lethal dose of JEV and showed an undetectable level of virus in brain tissue at 2 days post-infection. CONCLUSIONS: P10882, which targets sequence that is highly conserved across members of the JEV serocomplex, was previously shown to be effective in a mouse model of West Nile disease, and represents a candidate antiviral agent against members of the JEV serocomplex. PMID- 20299496 TI - Impact of 48 week lopinavir/ritonavir monotherapy on blood cell-associated HIV-1 DNA in the MONARK trial. AB - OBJECTIVES: To study the impact of protease inhibitor monotherapy on the HIV-1 blood reservoir in 72 antiretroviral-naive patients. PATIENTS AND METHODS: This was evaluated for 72 antiretroviral-naive patients included in the on-treatment analysis of the MONARK trial; 46 patients receiving lopinavir/ritonavir monotherapy and 26 patients receiving a triple therapy. HIV-DNA was quantified in whole blood, using real-time PCR. RESULTS: The decrease in HIV-DNA after 48 weeks of lopinavir/ritonavir monotherapy was similar to the decrease observed with triple therapy including lopinavir/ritonavir (-0.77 versus -0.69 log copies/10(6) leucocytes, respectively; P = 0.91). The HIV-DNA decrease was also similar in patients with a virological response in both arms (-0.69 versus -0.69 log copies/10(6) leucocytes, respectively). Interestingly, non-responders had a significantly higher baseline HIV-DNA load than responders in the monotherapy arm; 3.16 versus 2.86 log copies/10(6) leucocytes, respectively (P = 0.05). CONCLUSIONS: The MONARK data indicate that a lopinavir/ritonavir monotherapy regimen is potent against HIV blood reservoirs in antiretroviral-naive patients after 1 year of treatment, in comparison with a standard-of-care highly active antiretroviral therapy. This impact should be evaluated with other boosted protease inhibitor monotherapies. PMID- 20299497 TI - A human epidermal growth factor receptor 2 expression-based approach to neoadjuvant chemotherapy for operable breast cancer. AB - OBJECTIVE: We investigated the pathological effects of neoadjuvant chemotherapy based on the human epidermal growth factor receptor 2 in operable breast cancer. METHODS: This prospective clinical study was a pilot involving 63 female patients. Before surgery, patients with tumors overexpressing human epidermal growth factor receptor 2 received four cycles of 60 mg/m(2) anthracycline and 600 mg/m(2) cyclophosphamide every 3 weeks, whereas those whose tumors did not overexpress human epidermal growth factor receptor 2 received four cycles of 75 mg/m(2) docetaxel and 600 mg/m(2) cyclophosphamide every 3 weeks. A quasi pathological complete response (i.e. absence of invasive tumor or only focal residual tumor cells) was the primary endpoint, with compliance and predictors for each regimen as secondary endpoints. If a quasi-pathological complete response was not achieved, then crossover to the alternative treatment was recommended. RESULTS: The quasi-pathological complete response rate was 36.5% (23 of 63) overall, 27.8% (5 of 18) for the anthracycline and cyclophosphamide regimen and 40.0% (18 of 45) for the docetaxel and cyclophosphamide regimen. Docetaxel and cyclophosphamide treatment induced a quasi-pathological complete response in most patients with triple-negative tumors (15 of 19). The relative dose intensity was 97.3% for the anthracycline and cyclophosphamide regimen and 96.6% for the docetaxel and cyclophosphamide regimen. Quasi-pathological complete response to the docetaxel and cyclophosphamide regimen was associated with low estrogen receptor and progesterone receptor expression and high MIB-1 and topoisomerase IIalpha expression, in univariate analyses, but only with low estrogen receptor expression in multivariate analysis. CONCLUSIONS: Selecting neoadjuvant chemotherapy regimens on the basis of individual human epidermal growth factor receptor 2 status improved efficacy, with docetaxel and cyclophosphamide treatment showing particular promise in tumors with the potential to be highly malignant. PMID- 20299498 TI - Trends of the primary therapy for patients with prostate cancer in Nara uro oncological research group (NUORG): a comparison between the CaPSURE data and the NUORG data. AB - OBJECTIVE: We assessed the variations in stage, prostate specific antigen at diagnosis, Gleason score, risk classification and primary therapy in Japanese prostate cancer patients, and compared with those of the US patients. METHODS: Between 2004 and 2006, the distribution of primary therapy and clinical characteristics of 2303 newly diagnosed patients at Nara Medical University and its 23 affiliated hospitals were assessed to compare with those of the Cancer of the Prostate Strategic Urological Research Endeavor data and to clarify the differences in data between the USA and Japan. RESULTS: The proportions of clinical T stage of 3-4, prostate specific antigen at diagnosis >20 ng/ml, Gleason score of 8-10 and high-risk group were greater in our study than those of the Cancer of the Prostate Strategic Urological Research Endeavor data (T3-4, 26.2 vs. 3.5-11.8%; prostate-specific antigen, 34.1 vs. 8.1-27.0%; Gleason score, 29.3 vs. 9.7-12.1%). Regarding the primary treatments, 51% of patients received primary androgen deprivation therapy, 30% underwent radical prostatectomy, 14% received radiation therapy and 2% had watchful waiting in our study, while the corresponding figures in the Cancer of the Prostate Strategic Urological Research Endeavor data were: radical prostatectomy, 44%; radiation therapy, 23%; primary androgen deprivation therapy 20% and watchful waiting 10%. CONCLUSIONS: The Japanese prostate cancer patients still have higher prostate-specific antigen at diagnosis, higher Gleason score and higher clinical stage than the US patients. The trends of primary therapy for prostate cancer were different from those in the USA. The higher rate of primary androgen deprivation therapy is characteristic for the Japanese patients. PMID- 20299499 TI - A comparison of multimodality treatment: two or four courses of paclitaxel plus cisplatin or S-1 plus cisplatin followed by surgery for locally advanced gastric cancer, a randomized Phase II trial (COMPASS). AB - This randomized Phase II trial compares neoadjuvant chemotherapy of two or four courses of S-1 (1 M tegafur-0.4 M gimestat-1 M ostat potassium) plus cisplatin or paclitaxel plus cisplatin by a two-by-two factorial design for patients with macroscopically resectable locally advanced gastric cancer. The primary endpoint is the 3-year overall survival. The sample size is 60-80 in a total for two hypotheses of the superiority of four courses to two courses and the superiority of paclitaxel plus cisplatin to S-1 plus cisplatin. In both arms, S-1 is strongly recommended post-operatively for at least 6 months but no adjuvant chemotherapy is permitted other than S-1 until recurrence. This trial could appraise more suitable cycles and regimen as neoadjuvant chemotherapy for gastric cancer. PMID- 20299500 TI - How can health promotion interventions be adapted for minority ethnic communities? Five principles for guiding the development of behavioural interventions. AB - The term 'culturally sensitive' is often used to describe interventions adapted for minority ethnic communities. However, understanding of strategies for adapting behavioural interventions for such communities is limited. The questions addressed in this paper are: What are the main strategies for adapting interventions to reduce coronary heart disease (CHD) for minority ethnic communities? Why have interventions been adapted in these ways? A systematic review was carried out to investigate interventions for preventing CHD, including promoting physical activity, smoking cessation and healthier diets in Pakistani, Chinese and Indian communities in countries where these groups are minorities. International databases and key websites were searched, and 23 477 titles and abstracts were initially identified. Seventeen papers met inclusion and quality criteria. A 'meta-ethnographic' approach to data synthesis was employed to identify underlying principles for adapting interventions. The rationale underpinning adaptations is not made explicit in individual studies, limiting generalizability. Five principles for adapting behavioural interventions for minority ethnic communities were identified: (i) use community resources to publicize the intervention and increase accessibility; (ii) identify and address barriers to access and participation; (iii) develop communication strategies which are sensitive to language use and information requirements; (iv) work with cultural or religious values that either promote or hinder behavioural change; and (v) accommodate varying degrees of cultural identification. While the principles require further testing and verification, they have been generated through a systematic approach to study identification, quality appraisal and data synthesis. This represents significant progress in advancing understanding of adapted behavioural interventions for minority ethnic communities. PMID- 20299501 TI - Hospital outbreak of Pseudomonas aeruginosa producing extended-spectrum oxacillinase OXA-19. PMID- 20299502 TI - Three cases of Arcanobacterium pyogenes-associated soft tissue infection. AB - Arcanobacterium pyogenes is an established but often unrecognized human pathogen. A. pyogenes may also be misidentified as Arcanobacterium haemolyticum, which gives remarkably similar results in conventional biochemical tests. In this study, we have reported three cases of wound infections associated with A. pyogenes and also on the bacteriological characteristics which are relevant for identification of these isolates. The negative reverse CAMP test, the ability to produce acid from xylose and to hydrolyse gelatin and the positive beta glucuronidase test clearly differentiated A. pyogenes from other closely related species. All three isolates were uniformly susceptible to penicillin, ampicillin, amoxicillin-clavulanic acid, ceftriaxone and gentamicin, variably susceptible to tetracycline and erythromycin and uniformly resistant to cotrimoxazole. Only a few confirmed cases have been reported throughout the world and therefore the diagnostic evaluation of this organism is emphasized. PMID- 20299503 TI - Aspergillus niger: an unusual cause of invasive pulmonary aspergillosis. AB - Infections due to Aspergillus species cause significant morbidity and mortality. Most are attributed to Aspergillus fumigatus, followed by Aspergillus flavus and Aspergillus terreus. Aspergillus niger is a mould that is rarely reported as a cause of pneumonia. A 72-year-old female with chronic obstructive pulmonary disease and temporal arteritis being treated with steroids long term presented with haemoptysis and pleuritic chest pain. Chest radiography revealed areas of heterogeneous consolidation with cavitation in the right upper lobe of the lung. Induced bacterial sputum cultures, and acid-fast smears and cultures were negative. Fungal sputum cultures grew A. niger. The patient clinically improved on a combination therapy of empiric antibacterials and voriconazole, followed by voriconazole monotherapy. After 4 weeks of voriconazole therapy, however, repeat chest computed tomography scanning showed a significant progression of the infection and near-complete necrosis of the right upper lobe of the lung. Serum voriconazole levels were low-normal (1.0 microg ml(-1), normal range for the assay 0.5-6.0 microg ml(-1)). A. niger was again recovered from bronchoalveolar lavage specimens. A right upper lobectomy was performed, and lung tissue cultures grew A. niger. Furthermore, the lung histopathology showed acute and organizing pneumonia, fungal hyphae and oxalate crystallosis, confirming the diagnosis of invasive A. niger infection. A. niger, unlike A. fumigatus and A. flavus, is less commonly considered a cause of invasive aspergillosis (IA). The finding of calcium oxalate crystals in histopathology specimens is classic for A. niger infection and can be helpful in making a diagnosis even in the absence of conidia. Therapeutic drug monitoring may be useful in optimizing the treatment of IA given the wide variations in the oral bioavailability of voriconazole. PMID- 20299504 TI - Multilocus variable-number tandem repeat analysis of Vibrio cholerae O1 El Tor strains harbouring classical toxin B. AB - Atypical Vibrio cholerae O1 strains - hybrid strains (strains that cannot be classified either as El Tor or classical biotype) and altered strains (El Tor biotype strains that produce classical cholera toxin) - are currently prevalent in Asia and Africa. A total of 74 hybrid and altered strains that harboured classical cholera toxin were investigated by multilocus variable-number tandem repeat analysis (MLVA). The results showed that the hybrid/altered strains could be categorized into three groups and that they were distant from the El Tor strain responsible for the seventh cholera pandemic. Hybrid/altered strains with a tandem repeat of the classical CTX prophage on the small chromosome were divided into two MLVA groups (group I: Mozambique/Bangladesh group; group III: Vietnam group), and altered strains with the RS1-CTX prophage containing the El Tor type rstR and classical ctxB on the large chromosome were placed in two MLVA groups (group II: India/Bangladesh group; group III: India/Vietnam group). PMID- 20299505 TI - Allelic variation in colonization factor CS6 of enterotoxigenic Escherichia coli isolated from patients with acute diarrhoea and controls. AB - Colonization factor antigens (CFAs) are important virulence factors in enterotoxigenic Escherichia coli (ETEC). Using a multiplex PCR and RT-PCR, this study tested the presence of common colonization factor-encoding genes and their expression in 50 ETEC strains isolated from stool specimens. The samples were from patients (children) with acute diarrhoea (cases) admitted to the Infectious Disease Hospital (Kolkata, India) and from normal children (controls) under 5 years of age from the community. The results indicated that coli surface antigen 6 (CS6) was the most prevalent CFA (78 %) expressed by these ETEC strains. Sequence analysis of both of the CS6 structural genes, i.e. cssA and cssB, in different ETEC isolates revealed the presence of point mutations in a systematic fashion. Based on the analysis of these variations, it was found that CssA had three alleles and CssB had two. Based on the allelic variations, subtyping of CS6 into AIBI, AIIBII, AIIIBI, AIBII and AIIIBII is proposed. The point mutations in the different alleles were reflected in a partial alteration in the secondary structure of both subunits, as determined by computational analysis. The functional significance of these changes was confirmed with cellular binding studies in Caco-2 cells with representative ETEC isolates. CS6 with AI or AIII allelic subtypes showed a higher binding capacity than AII, whereas BI showed stronger binding than BII. The AII and BII alleles were mostly detected in controls rather than in cases. The antibody specificity of BI and BII also varied due to alteration of the amino acids. Thus, CS6 variants are formed as a result of different allelic combinations of CssA and CssB, and these changes at the functional level might be important in the development of an effective ETEC vaccine. PMID- 20299506 TI - Silicone colonization by non-Candida albicans Candida species in the presence of urine. AB - Urinary tract infections (UTIs) are the most common nosocomial infections and 80 % are related to the use of urinary catheters. Furthermore, Candida species are responsible for around 15 % of UTIs and an increasing involvement of non-Candida albicans Candida (NCAC) species (e.g. Candida glabrata, Candida tropicalis and Candida parapsilosis) has been recognized. Given the fact that silicone is frequently used in the manufacture of urinary catheters, the aim of this work was to compare both the adhesion and biofilm formation on silicone of different urinary clinical isolates of NCAC species (i.e. C. glabrata, C. tropicalis and C. parapsilosis) in the presence of urine. Several clinical isolates of NCAC species recovered from patients with UTIs, together with reference strains of each species, were examined. Adhesion and biofilm formation were performed in artificial urine and the biofilm biomass was assessed by crystal violet staining. Hydrophobicity and surface charge of cells was determined by measuring contact angles and zeta potential, respectively. The number of viable cells in biofilms was determined by enumeration of c.f.u. after appropriate culture. The biofilm structure was also examined by confocal laser scanning microscopy (CLSM). The results showed that all isolates adhered to silicone in a species- and strain dependent manner with C. parapsilosis showing the lowest and C. glabrata the highest levels of adhesion. However, these differences in adhesion abilities cannot be correlated with surface properties since all strains examined were hydrophilic and exhibited a similar zeta potential. Despite a higher number of cultivable cells being recovered after 72 h of incubation, stronger biofilm formation was not observed and CLSM showed an absence of extracellular polymeric material for all isolates examined. In summary, this work demonstrated that all tested NCAC species were able to adhere to and survive on silicone in the presence of urine. Furthermore, C. glabrata strains presented higher colonization abilities than C. tropicalis and C. parapsilosis strains, a fact that might explain the larger role of C. glabrata colonization and disseminated infections in hospitalized and catheterized patients. PMID- 20299507 TI - Fatal vancomycin- and linezolid-resistant Enterococcus faecium sepsis in a child undergoing allogeneic haematopoietic stem cell transplantation for beta thalassaemia major. AB - Recently vancomycin-resistant and sporadically linezolid-resistant Enterococcus species have been described in adults. We report what we believe to be the first case of a child with prolonged bone marrow aplasia following haematopoietic stem cell transplantation developing a fatal sepsis caused by Enterococcus faecium resistant to glycopeptides and linezolid. PMID- 20299508 TI - Discovery of a small-molecule type II inhibitor of wild-type and gatekeeper mutants of BCR-ABL, PDGFRalpha, Kit, and Src kinases: novel type II inhibitor of gatekeeper mutants. AB - Many clinically validated kinases, such as BCR-ABL, c-Kit, PDGFR, and EGFR, become resistant to adenosine triphosphate-competitive inhibitors through mutation of the so-called gatekeeper amino acid from a threonine to a large hydrophobic amino acid, such as an isoleucine or methionine. We have developed a new class of adenosine triphosphate competitive inhibitors, exemplified by HG-7 85-01, which is capable of inhibiting T315I- BCR-ABL (clinically observed in chronic myeloid leukemia), T670I-c-Kit (clinically observed in gastrointestinal stromal tumors), and T674I/M-PDGFRalpha (clinically observed in hypereosinophilic syndrome). HG-7-85-01 is unique among all currently reported kinase inhibitors in having the ability to accommodate either a gatekeeper threonine, present in the wild-type forms of these kinases, or a large hydrophobic amino acid without becoming a promiscuous kinase inhibitor. The distinctive ability of HG-7-85-01 to simultaneously inhibit both wild-type and mutant forms of several kinases of clinical relevance is an important step in the development of the next generation of tyrosine kinase inhibitors. PMID- 20299509 TI - Transfusion of red blood cells after prolonged storage produces harmful effects that are mediated by iron and inflammation. AB - Although red blood cell (RBC) transfusions can be lifesaving, they are not without risk. In critically ill patients, RBC transfusions are associated with increased morbidity and mortality, which may increase with prolonged RBC storage before transfusion. The mechanisms responsible remain unknown. We hypothesized that acute clearance of a subset of damaged, stored RBCs delivers large amounts of iron to the monocyte/macrophage system, inducing inflammation. To test this in a well-controlled setting, we used a murine RBC storage and transfusion model to show that the transfusion of stored RBCs, or washed stored RBCs, increases plasma nontransferrin bound iron (NTBI), produces acute tissue iron deposition, and initiates inflammation. In contrast, the transfusion of fresh RBCs, or the infusion of stored RBC-derived supernatant, ghosts, or stroma-free lysate, does not produce these effects. Furthermore, the insult induced by transfusion of stored RBC synergizes with subclinical endotoxinemia producing clinically overt signs and symptoms. The increased plasma NTBI also enhances bacterial growth in vitro. Taken together, these results suggest that, in a mouse model, the cellular component of leukoreduced, stored RBC units contributes to the harmful effects of RBC transfusion that occur after prolonged storage. Nonetheless, these findings must be confirmed by prospective human studies. PMID- 20299511 TI - Phase 1/2 and extension study of velaglucerase alfa replacement therapy in adults with type 1 Gaucher disease: 48-month experience. AB - Enzyme replacement therapy is the standard of care for symptomatic Gaucher disease. Velaglucerase alfa is a human beta-glucocerebrosidase produced in a well characterized human cell line. A 9-month phase 1/2 open-label, single-center trial and ongoing extension study were conducted to evaluate safety and efficacy of velaglucerase alfa. Twelve symptomatic adult type 1 Gaucher patients (intact spleens) received velaglucerase alfa (60 U/kg per infusion) during phase 1/2. An extension study was offered to patients completing the trial; step-wise dose reduction (to 30 U/kg per infusion) was instituted. Eleven patients completed phase 1/2; 10 entered the extension; 9 patients reached 39 months of extension. No drug-related serious adverse events or withdrawals, and no antibodies were observed. Home therapy was successfully implemented during the extension. Statistically significant improvements (P < .004) were noted in mean percentage change from baseline to 9 months and baseline to 48 months for hemoglobin (+19.2%, +21.7%, respectively), platelet counts (+67.6%, +157.8%, respectively), normalized liver volume (-18.2%, -42.8%, respectively), and normalized spleen volume (-49.5%, -79.3%, respectively). These significant clinical changes and safety profile led to phase 3 trials and highlight the potential of velaglucerase alfa as alternative therapy for type 1 Gaucher disease. The extension trial is registered at http://www.clinicaltrials.gov as NCT00391625. PMID- 20299512 TI - Members of the microRNA-17-92 cluster exhibit a cell-intrinsic antiangiogenic function in endothelial cells. AB - MicroRNAs are endogenously expressed small noncoding RNAs that regulate gene expression on the posttranscriptional level. The miR-17-92 cluster (encoding miR 17, -18a, -19a/b, -20a, and miR-92a) is highly expressed in tumor cells and is up regulated by ischemia. Whereas miR-92a was recently identified as negative regulator of angiogenesis, the specific functions of the other members of the cluster are less clear. Here we demonstrate that overexpression of miR-17, -18a, 19a, and -20a significantly inhibited 3-dimensional spheroid sprouting in vitro, whereas inhibition of miR-17, -18a, and -20a augmented endothelial cell sprout formation. Inhibition of miR-17 and miR-20a in vivo using antagomirs significantly increased the number of perfused vessels in Matrigel plugs, whereas antagomirs that specifically target miR-18a and miR-19a were less effective. However, systemic inhibition of miR-17/20 did not affect tumor angiogenesis. Further mechanistic studies showed that miR-17/20 targets several proangiogenic genes. Specifically, Janus kinase 1 was shown to be a direct target of miR-17. In summary, we show that miR-17/20 exhibit a cell-intrinsic antiangiogenic activity in endothelial cells. Inhibition of miR-17/20 specifically augmented neovascularization of Matrigel plugs but did not affect tumor angiogenesis indicating a context-dependent regulation of angiogenesis by miR-17/20 in vivo. PMID- 20299510 TI - Dual inhibition of PI3K and mTOR inhibits autocrine and paracrine proliferative loops in PI3K/Akt/mTOR-addicted lymphomas. AB - Primary effusion lymphoma (PEL) constitutes a subset of non-Hodgkin lymphoma whose incidence is highly increased in the context of HIV infection. Kaposi sarcoma-associated herpesvirus is the causative agent of PEL. The phosphatidylinositol 3-kinase (PI3K) signaling pathway plays a critical role in cell proliferation and survival, and this pathway is dysregulated in many different cancers, including PEL, which display activated PI3K, Akt, and mammalian target of rapamycin (mTOR) kinases. PELs rely heavily on PI3K/Akt/mTOR signaling, are dependent on autocrine and paracrine growth factors, and also have a poor prognosis with reported median survival times of less than 6 months. We compared different compounds that inhibit the PI3K/Akt/mTOR pathway in PEL. Although compounds that modulated activity of only a single pathway member inhibited PEL proliferation, the use of a novel compound, NVP-BEZ235, that dually inhibits both PI3K and mTOR kinases was significantly more efficacious in culture and in a PEL xenograft tumor model. NVP-BEZ235 was effective at low nanomolar concentrations and has oral bioavailability. We also report a novel mechanism for NVP-BEZ235 involving the suppression of multiple autocrine and paracrine growth factors required for lymphoma survival. Our data have broad applicability for the treatment of cytokine-dependent tumors with PI3K/mTOR dual inhibitors. PMID- 20299515 TI - Inhibition of phagocytosis in HIV-1-infected macrophages relies on Nef-dependent alteration of focal delivery of recycling compartments. AB - Phagocytosis in macrophages is receptor mediated and relies on actin polymerization coordinated with the focal delivery of intracellular membranes that is necessary for optimal phagocytosis of large particles. Here we show that phagocytosis by various receptors was inhibited in primary human macrophages infected with wild-type HIV-1 but not with a nef-deleted virus. We observed no major perturbation of F-actin accumulation, but adaptor protein 1 (AP1)-positive endosome recruitment was inhibited in HIV-1-infected cells. Expression of negative factor (Nef) was sufficient to inhibit phagocytosis, and myristoylation as well as the LL and DD motifs involved in association of Nef with AP complexes were important for this inhibition. We observed that Nef interferes with AP1 in association with membranes and/or with a cleaved regulatory form of AP1. Finally, an alteration of the recruitment of vesicle-associated membrane protein (VAMP3)- and tumor necrosis factor-alpha (TNFalpha)-positive recycling endosomes regulated by AP1, but not of VAMP7-positive late endosomes, was observed in phagocytic cups of HIV-1-infected macrophages. We conclude that HIV-1 impairs optimal phagosome formation through Nef-dependent perturbation of the endosomal remodeling relying on AP1. We therefore identified a mechanism of macrophage function down regulation in infected cells. PMID- 20299513 TI - Arterial and venous thrombosis in monoclonal gammopathy of undetermined significance and multiple myeloma: a population-based study. AB - Patients with multiple myeloma (MM) have an increased risk of venous thrombosis. Interestingly, excess risk of venous thromboembolism has been observed among patients with monoclonal gammopathy of undetermined significance (MGUS). Using population-based data from Sweden, we assessed the risks of venous and arterial thrombosis in 18,627 MM and 5326 MGUS patients diagnosed from 1958 to 2006, compared with 70,991 and 20,161 matched controls, respectively. At 1, 5, and 10 years after MM diagnosis, there was an increased risk of venous thrombosis: hazard ratios (95% confidence intervals) were 7.5 (6.4-8.9), 4.6 (4.1-5.1), and 4.1 (3.8-4.5), respectively. The corresponding results for arterial thrombosis were 1.9 (1.8-2.1), 1.5 (1.4-1.6), and 1.5 (1.4-1.5). At 1, 5, and 10 years after MGUS diagnosis, hazard ratios were 3.4 (2.5-4.6), 2.1 (1.7-2.5), and 2.1 (1.8 2.4) for venous thrombosis. The corresponding risks for arterial thrombosis were 1.7 (1.5-1.9), 1.3 (1.2-1.4), and 1.3 (1.3-1.4). IgG/IgA (but not IgM) MGUS patients had increased risks for venous and arterial thrombosis. Risks for thrombosis did not vary by M-protein concentration (> 10.0 g/L or < 10.0 g/L) at diagnosis. MGUS patients with (vs without) thrombosis had no excess risk of MM or Waldenstrom macroglobulinemia. Our findings are of relevance for future studies and for improvement of thrombosis prophylaxis strategies. PMID- 20299516 TI - Target recognition-induced NK-cell responses. PMID- 20299514 TI - E-selectin engages PSGL-1 and CD44 through a common signaling pathway to induce integrin alphaLbeta2-mediated slow leukocyte rolling. AB - In inflamed venules, neutrophils rolling on E-selectin induce integrin alpha(L)beta(2)-dependent slow rolling on intercellular adhesion molecule-1 by activating Src family kinases (SFKs), DAP12 and Fc receptor-gamma (FcRgamma), spleen tyrosine kinase (Syk), and p38. E-selectin signaling cooperates with chemokine signaling to recruit neutrophils into tissues. Previous studies identified P-selectin glycoprotein ligand-1 (PSGL-1) as the essential E-selectin ligand and Fgr as the only SFK that initiate signaling to slow rolling. In contrast, we found that E-selectin engagement of PSGL-1 or CD44 triggered slow rolling through a common, lipid raft-dependent pathway that used the SFKs Hck and Lyn as well as Fgr. We identified the Tec kinase Bruton tyrosine kinase as a key signaling intermediate between Syk and p38. E-selectin engagement of PSGL-1 was dependent on its cytoplasmic domain to activate SFKs and slow rolling. Although recruiting phosphoinositide-3-kinase to the PSGL-1 cytoplasmic domain was reported to activate integrins, E-selectin-mediated slow rolling did not require phosphoinositide-3-kinase. Studies in mice confirmed the physiologic significance of these events for neutrophil slow rolling and recruitment during inflammation. Thus, E-selectin triggers common signals through distinct neutrophil glycoproteins to induce alpha(L)beta(2)-dependent slow rolling. PMID- 20299517 TI - Cyclophosphamide in aplastic anemia? PMID- 20299518 TI - V(D)J recombination and staggered DNA breaks: guilty again. PMID- 20299519 TI - Macrophages give Gas(6) to cancer. PMID- 20299520 TI - If Virchow were to meet Newton. PMID- 20299521 TI - A novel antiphospholipid antibody agent? PMID- 20299522 TI - Pandemic influenza A (H1N1) virus infections in children with sickle cell disease. PMID- 20299523 TI - Update on dental nanocomposites. AB - Dental resin-composites are comprised of a photo-polymerizable organic resin matrix and mixed with silane-treated reinforcing inorganic fillers. In the development of the composites, the three main components can be modified: the inorganic fillers, the organic resin matrix, and the silane coupling agents. The aim of this article is to review recent studies of the development of dental nanocomposites and their clinical applications. In nanocomposites, nanofillers are added and distributed in a dispersed form or as clusters. For increasing the mineral content of the tooth, calcium and phosphate ion-releasing composites and fluoride-releasing nanocomposites were developed by the addition of DCPA-whiskers or TTCP-whiskers or by the use of calcium fluoride or kaolinite. For enhancing mechanical properties, nanocomposites reinforced with nanofibers or nanoparticles were investigated. For reducing polymerization shrinkage, investigators modified the resin matrix by using methacrylate and epoxy functionalized nanocomposites based on silsesquioxane cores or epoxy-resin-based nanocomposites. The effects of silanization were also studied. Clinical consideration of light-curing modes and mechanical properties of nanocomposites, especially strength durability after immersion, was also addressed. PMID- 20299524 TI - Bcl2 is not required for the development and maintenance of leukemia stem cells in mice. AB - The existence of leukemia stem cells (LSCs) responsible for tumor maintenance has been firmly established. Therefore, therapeutic targeting of these LSCs may have a profound impact on cancer eradication. The anti-apoptotic protein Bcl2 has been proposed as a therapeutic target, but its role in LSC biology has not been investigated. In order to understand the role of Bcl2 in LSC generation and maintenance, we have taken advantage of our Sca1-BCRABLp210 mouse model of human chronic myeloid leukemia and bcl2 gene-targeted mice. This study provides genetic evidence that the inhibition of Bcl2 is not critical for the generation, selection or maintenance of the tumor initiating and maintaining cells in mice. PMID- 20299525 TI - Wheel running, skeletal muscle aerobic capacity and 1-methyl-1-nitrosourea induced mammary carcinogenesis in the rat. AB - Emerging evidence indicates that intrinsic differences and induced changes in aerobic capacity are probably to play a critical role in the development of chronic diseases like cancer. This study was initiated: (i) to determine how citrate synthase activity, which is routinely used as a marker of aerobic capacity and mitochondrial density in skeletal muscle, was affected by voluntary running on either a motorized activity wheel or a non-motorized free wheel and (ii) to investigate the association between aerobic capacity and the carcinogenic response induced in the mammary gland by intraperitoneal injection of 1-methyl-1 nitrosurea. Overall, wheel running reduced cancer incidence (96 versus 72%, P = 0.0006) and the number of cancers per animal (2.84 versus 1.78, P < 0.0001) and induced citrate synthase activity (276 versus 353 U/mg, P < 0.0001, sedentary control versus wheel running,respectively). Both motorized and free wheel running increased citrate synthase activity (373 +/- 24, 329 +/- 11 and 276 +/- 9 U/mg protein, P < 0.0001) and reduced the average number of cancers per rat (2.84, 1.96 and 1.63, P < 0.01), sedentary control, free wheel and motorized wheel, respectively. However, regression analyses failed to provide evidence of a significant association between citrate synthase activity and either cancer incidence or cancer multiplicity. Citrate synthase activity is a single measure in a complex pathway that determines aerobic capacity. The multifaceted nature of intrinsic and inducible aerobic capacity limits the usefulness of citrate synthase activity alone in elucidating the relationship between aerobic capacity and the carcinogenic response. PMID- 20299527 TI - Inhibition of mTORC1 signaling reduces tumor growth but does not prevent cancer progression in a mouse model of thyroid cancer. AB - Selective drugs targeting dysregulated oncogenic pathways are promising cancer therapies. Because the mammalian target of rapamycin complex 1 (mTORC1) pathway is hyperactivated in human follicular thyroid cancer (FTC), we hypothesized that its inhibition could block cancer development and progression. We, therefore, analyzed the effect of a treatment with a specific mTORC1 inhibitor (RAD001) in a faithful mouse model of FTC with constitutive mTORC1 activation (TRbeta(PV/PV)Pten(+/-) mice). The treatment did not prevent capsular and vascular invasion of the thyroid and the occurrence of lung metastasis. However, it substantially decelerated thyroid tumor growth, thereby prolonging TRbeta(PV/PV)Pten(+/-) mouse life span. RAD001 efficiently inhibited mTORC1 activity, as shown by the reduced phosphorylation of its downstream targets involved in the activity of the translation machinery, such as ribosomal S6 kinase (p70(S6K)), eukaryotic translation initiation factor 4E binding protein (4E-BP1) and the eukaryotic translation initiation factors eIF-4B and eIF-4G. Whereas mTORC1 signaling inhibition did not alter cell apoptosis, it induced a significant decrease in cell proliferation that was associated with the reduced abundance and altered activity of key regulators of cell cycle progression. Altogether, our data indicate that mTORC1 signaling plays a major role in the integration of the mitogenic signal in FTC. Therefore, our preclinical study with a relevant mouse model of FTC demonstrates for the first time that RAD001 efficaciously stabilizes cancer growth although it does not prevent its fatal outcome. In conclusion, our work underscores that in the treatment of FTC patients, RAD001 can only be used in combination with drugs and therapies inducing tumor shrinkage and blocking metastasis. PMID- 20299529 TI - Deficient and dysfunctional regulatory T cells in the lungs of chronic beryllium disease subjects. AB - RATIONALE: Chronic beryllium disease (CBD) is a CD4(+) T cell-mediated disorder characterized by persistent lung inflammation. Naturally occurring regulatory T (T(reg)) cells modulate adaptive immune responses. The role of this T-cell subset in beryllium-induced lung disease is unknown. OBJECTIVES: The aim of this study was to determine whether dysfunctional T(reg) cells in the lung contribute to the "unchecked" inflammatory response that characterizes CBD. METHODS: Using blood and bronchoalveolar lavage (BAL) cells from normal control subjects and individuals with beryllium-induced disease, we determined the frequency and function of naturally occurring T(reg) cells. MEASUREMENTS AND MAIN RESULTS: A significantly decreased percentage and expression of FoxP3 in BAL CD4(+) T cells from CBD patients compared with beryllium-sensitized subjects was seen, and the percentage of FoxP3-expressing CD4(+) T(reg) cells in BAL inversely correlated with disease severity. In contrast to blood T(reg) cells derived from beryllium sensitized subjects and patients with CBD that completely suppressed blood responder T-cell proliferation, BAL FoxP3-expressing T(reg) cells from patients with CBD are unable to suppress anti-CD3-mediated BAL T-cell proliferation. Mixing studies showed that blood T(reg) cells are capable of suppressing autologous BAL responder T cells. Conversely, BAL CD4(+) T(reg) cells are incapable of suppressing blood T cells, confirming that the failure of BAL T(reg) cells to suppress T-cell proliferation is caused by a dysfunctional T(reg) cell subset and not by resistance of BAL effector T cells to suppression. CONCLUSIONS: These findings suggest that the deficient and dysfunctional T(reg) cells in the lung of patients with CBD contribute to the persistent inflammatory response in this disease. PMID- 20299531 TI - Tumor necrosis factor-{alpha} rs361525 polymorphism is associated with increased local production and downstream inflammation in chronic obstructive pulmonary disease. AB - RATIONALE: Chronic obstructive pulmonary disease (COPD) has a genetic component, explaining susceptibility. Tumor necrosis factor (TNF)-alpha polymorphisms have been associated with COPD, but it is unclear if genotype influences clinical phenotype, protein expression, and bioactivity. OBJECTIVES: To determine if a functional polymorphism was important by assessing TNF-alpha expression and activity and its association with clinical severity over time. METHODS: Patients with COPD with rs361525 polymorphism were matched to patients with COPD without rs361525 polymorphism. TNF-alpha, its antagonists, and downstream mediators were measured in plasma and sputum. To determine TNF-alpha bioactivity, IL-8 secretion from primary bronchial epithelial cells (PBECs) was measured, and neutrophil migration was assessed using sputum from both subject groups in the presence and absence of TNF-alpha antibody. Subjects were followed annually and compared. MEASUREMENTS AND MAIN RESULTS: Patients with polymorphism had more chronic bronchitis, a lower body mass index, and a greater annual decline in FEV(1) than patients with COPD without rs361525 polymorphism. TNF-alpha concentrations were 100-fold higher in airway secretions from the patients with the rs361525 polymorphism, with no difference in TNF-alpha antagonists. Their lung secretions contained more IL-8 and myeloperoxidase, consistent with downstream inflammation. Sputum from patients with rs361525 polymorphism induced greater secretion of IL-8 from PBECs and increased neutrophil migration. These effects could be abrogated by TNF-alpha antibody, demonstrating the bioactivity of TNF-alpha in lung secretions from this group. CONCLUSIONS: This TNF-alpha polymorphism is associated with clinical features of disease including progression. There is clear evidence of TNF-alpha overexpression and bioactivity with neutrophilic inflammation. The polymorphism is likely to be a factor that influences a COPD disease phenotype and its progression. PMID- 20299530 TI - Progressive 3q amplification consistently targets SOX2 in preinvasive squamous lung cancer. AB - RATIONALE: Amplification of distal 3q is the most common genomic aberration in squamous lung cancer (SQC). SQC develops in a multistage progression from normal bronchial epithelium through dysplasia to invasive disease. Identifying the key driver events in the early pathogenesis of SQC will facilitate the search for predictive molecular biomarkers and the identification of novel molecular targets for chemoprevention and therapeutic strategies. For technical reasons, previous attempts to analyze 3q amplification in preinvasive lesions have focused on small numbers of predetermined candidate loci rather than an unbiased survey of copy number variation. OBJECTIVES: To perform a detailed analysis of the 3q amplicon in bronchial dysplasia of different histological grades. METHODS: We use molecular copy-number counting (MCC) to analyze the structure of chromosome 3 in 19 preinvasive bronchial biopsy specimens from 15 patients and sequential biopsy specimens from 3 individuals. MEASUREMENTS AND MAIN RESULTS: We demonstrate that no low-grade lesions, but all high-grade lesions, have 3q amplification. None of seven low-grade lesions progressed clinically, whereas 8 of 10 patients with high grade disease progressed to cancer. We identify a minimum commonly amplified region on chromosome 3 consisting of 17 genes, including 2 known oncogenes, SOX2 and PIK3CA. We confirm that both genes are amplified in all high-grade dysplastic lesions tested. We further demonstrate, in three individuals, that the clinical progression of high-grade preinvasive disease is associated with incremental amplification of SOX2, suggesting this promotes malignant progression. CONCLUSIONS: These findings demonstrate progressive 3q amplification in the evolution of preinvasive SQC and implicate SOX2 as a key target of this dynamic process. PMID- 20299533 TI - Elevated exhaled nitric oxide in high-risk neonates precedes transient early but not persistent wheeze. AB - RATIONALE: Elevated fractional exhaled nitric oxide (Fe(NO)) concentration has been suggested to predict early childhood wheeze and sensitization. OBJECTIVES: To investigate the association between Fe(NO) in asymptomatic neonates and the development of wheeze patterns and atopic intermediary phenotypes in the first 6 years of life. METHODS: We measured Fe(NO) in 253 healthy 1-month-old neonates from the Copenhagen Prospective Study on Asthma in Childhood birth cohort and monitored prospectively wheezy episodes by daily diary cards during the first 6 years of life. Total IgE, specific IgE, and blood eosinophil count were assessed at age 6 months, 4 years, and 6 years. Associations were studied by Cox regression, logistic regression, and generalized linear models. MEASUREMENTS AND MAIN RESULTS: Increased neonatal Fe(NO) level was significantly associated with the development of recurrent wheeze in the first year of life (hazard ratio, 2.63; 95% confidence interval, 1.1 to 6.2; P = 0.026) but not thereafter. The association was unaffected by environmental tobacco smoke exposure. Fe(NO) was not associated with elevated levels of total IgE, specific IgE, or blood eosinophil count at any age point and was unrelated to neonatal lung function. CONCLUSIONS: An elevated Fe(NO) level in asymptomatic neonates born to mothers with asthma preceded the development of transient early wheezing, but not persistent wheezing during preschool age, and was unrelated to atopy. This suggests an early disease process other than small airway caliber contributing to the transient wheezing phenotype. PMID- 20299532 TI - A prospective multicenter study of adrenal function in critically ill children. AB - RATIONALE: Adrenal insufficiency is a clinical condition associated with fluid- and catecholamine-resistant hypotension. OBJECTIVES: The objectives of this study were to determine the prevalence of adrenal insufficiency, risk factors and potential mechanisms for its development, and its association with clinically important outcomes in critically ill children. METHODS: A prospective, cohort study was conducted from 2005 to 2008 in seven tertiary-care, pediatric intensive care units in Canada on patients up to 17 years of age with existing vascular access. Adrenocorticotropic hormone stimulation tests (1 microg) were performed and adrenocorticotropic hormone levels measured in all participants. MEASUREMENTS AND MAIN RESULTS: A total of 381 patients had adrenal testing on admission. The prevalence of adrenal insufficiency was 30.2% (95% confidence interval, 25.9 35.1). Patients with adrenal insufficiency had higher baseline cortisol levels (28.6 microg/dl vs. 16.7 microg/dl, P < 0.001) and were significantly older (11.5 yr vs. 2.3 yr, P < 0.001) than those without adrenal insufficiency. Adrenal insufficiency was associated with an increased need for catecholamines (P < 0.001) and more fluid boluses (P = 0.026). The sensitivity and specificity of the low-dose adrenocorticotropic hormone stimulation test were 100% and 84%, respectively. CONCLUSIONS: Adrenal insufficiency occurs in many disease conditions in critically ill children and is associated with an increased use of catecholamines and fluid boluses. It is likely multifactorial in etiology and is associated with high baseline cortisol levels. Further research is necessary to determine which of these critically ill children are truly cortisol deficient before any treatment recommendations can be made. PMID- 20299534 TI - Ethnic differences in perception of lung function: a factor in pediatric asthma disparities? AB - RATIONALE: Disparities in pediatric asthma exist in that Latino children have higher prevalence and greater morbidity from asthma than non-Latino white children. The factors behind these disparities are poorly understood, but ethnic related variations in children's ability to accurately recognize and report their pulmonary functioning may be a contributing process. OBJECTIVES: To determine (1) if differences exist between Latino and non-Latino white children's perceptual accuracy and (2) whether these differences are related to asthma outcomes. METHODS: Five hundred and twelve children, aged 7-16 years (290 island Puerto Ricans, 115 Rhode Island Latinos, and 107 Rhode Island non-Latino white children) participated in a 5-week home-based protocol in which twice daily they entered subjective estimates of their peak expiratory flow rate into a hand-held, programmable spirometer and then performed spirometry. Their accuracy was summarized as three perceptual accuracy scores. Demographic data, asthma severity, intelligence, emotional expression, and general symptom-reporting tendencies were assessed and covaried in analyses of the relationship of perceptual accuracy to asthma morbidity and health care use. MEASUREMENTS AND MAIN RESULTS: Younger age, female sex, lower intelligence, and poverty were associated with lower pulmonary function perception scores. Island Puerto Rican children had the lowest accuracy and highest magnification scores, followed by Rhode Island Latinos; both differed significantly from non-Latino white children. Perceptual accuracy scores were associated with most indices of asthma morbidity. CONCLUSIONS: Controlling for other predictive variables, ethnicity was related to pulmonary function perception ability, as Latino children were less accurate than non-Latino white children. This difference in perceptual ability may contribute to recognized asthma disparities. PMID- 20299536 TI - Obstructive sleep apnea syndrome is associated with deficits in verbal but not visual memory. AB - RATIONALE: Although cognitive deficits are well documented in patients with sleep apnea, the impact on memory remains unclear. OBJECTIVES: To test the hypotheses that (1) patients with obstructive sleep apnea have memory impairment and (2) memory impairment is commensurate with disease severity. METHODS: Patients with obstructive sleep apnea and healthy volunteers (apnea-hypopnea index <5 events/h) completed a test battery specially designed to differentiate between aspects of memory (semantic, episodic, and working) versus attention. Sleepiness was measured on the basis of the Epworth Sleepiness Scale and Oxford Sleep Resistance test. Memory performance in patients versus control subjects was compared (Mann Whitney U test; P < 0.01, Bonferroni corrected for multiple comparisons) and relationships between performance and disease severity were analyzed by linear regression. MEASUREMENTS AND MAIN RESULTS: Sixty patients and healthy control subjects matched for age (mean +/- SD: patients, 51 +/- 9 yr; control subjects, 50 +/- 9 yr) and education (patients, 14 +/- 3 yr; control subjects, 15 +/- 3 yr) participated. Patients demonstrated impaired Logical Memory Test results (immediate recall: patients, median [range], 36 [9-69]; control subjects, 43 [19 64], P = 0.0004; and delayed recall: patients, 22 [6-42]; control subjects, 27 [10-46]; P = 0.0001). There were minimal differences in attention, visual episodic, semantic, or working memory; patients performed better than control subjects on Spatial Span forward and backward. Regression analysis revealed that Logical Memory Test performance was not significantly related to disease severity after controlling for age, education, and sleepiness. CONCLUSIONS: Obstructive sleep apnea is associated with impairment in verbal, but not visual, memory. The impairment was present across a range of disease severity and was not explained by reduced attention. Such verbal memory impairment may affect daytime functioning and performance. PMID- 20299535 TI - Long-term cognitive and psychological outcomes in the awakening and breathing controlled trial. AB - RATIONALE: Studies have shown that reducing sedation of critically ill patients shortens time on the ventilator and in the intensive care unit (ICU). Little is known, however, of how such strategies affect long-term cognitive, psychological, and functional outcomes. OBJECTIVES: To determine the long-term effects of a wake up and breathe protocol that interrupts and reduces sedative exposure in the ICU. METHODS: In this a priori planned substudy conducted at one tertiary care hospital during the Awakening and Breathing Controlled Trial, a multicenter randomized controlled trial, we assessed cognitive, psychological, and functional/quality-of-life outcomes 3 and 12 months postdischarge among 180 medical ICU patients randomized to paired daily spontaneous awakening trials with spontaneous breathing trials (SBTs) or to sedation per usual care plus daily SBTs. MEASUREMENTS AND MAIN RESULTS: Cognitive impairment was less common in the intervention group at 3-month follow-up (absolute risk reduction, 20.2%; 95% confidence interval, 1.5-36.1%; P = 0.03) but not at 12-month follow-up (absolute risk reduction, -1.9%; 95% CI, -21.3 to 27.1%; P = 0.89). Composite cognitive scores, alternatively, were similar in the two groups at 3-month and 12-month follow-up (P = 0.80 and 0.61, respectively), as were symptoms of depression (P = 0.59 and 0.82) and posttraumatic stress disorder (P = 0.59 and 0.97). Activities of daily living, functional status, and mental and physical quality of life were similar between groups throughout follow-up. CONCLUSIONS: In this trial, management of mechanically ventilated medical ICU patients with a wake up and breathe protocol resulted in similar cognitive, psychological, and functional outcomes among patients tested 3 and 12 months post-ICU. The proven benefits of this protocol, including improved 1-year survival, were not offset by adverse long-term outcomes. Clinical trial registered with www.clinicaltrials.gov (NCT 00097630). PMID- 20299537 TI - Impact of panic disorder upon self-management educational goals in chronic obstructive pulmonary disease? AB - The rationale for introducing self-management plans for the whole chronic obstructive pulmonary disease (COPD) population is uncertain. This study's aim was to investigate whether people with panic disorder (PD), compared to non-panic disordered (NPD), derived additional educational or psychological benefits from having a self-management plan. The 24-week prospective study followed 76 participants hospitalized with an exacerbation of COPD. Participants completed mental health questionnaires including psychological measures of self-management plan impact. Subsequently, a nurse provided education for using a self-management plan. All participants were Plan naive irrespective of their PD status. Self management knowledge was assessed before introducing the Plan (baseline), 1 week post discharge and at 24 weeks. At baseline 28 (37%) of participants met the criteria for PD and this group had higher scores (better knowledge) for an impending (p < 0.05) and severe exacerbation (p < 0.05) and capacity to act during a severe exacerbation (p < 0.01). No interaction effect was found between PD and NPD scores over time, indicating that the PD's knowledge did not improve or deteriorate over time relative to the NPD. Evidence was mixed regarding the Plan's psychological impact. Self-management confidence improved in both groups. Amongst the PD group, perceived control of self-management tasks increased but so did body vigilance and distress about having COPD. There is mixed evidence regarding educational and psychological benefits of COPD self-management plans for people with PD. No additional educational advantages were found for the PD group. Plans may increase confidence and control over self-management but may also increase body vigilance and distress about having COPD. PMID- 20299538 TI - High prevalence of undiagnosed and severe chronic obstructive pulmonary disease at first hospital admission with acute exacerbation. AB - Chronic obstructive pulmonary disease (COPD) is a common cause of acute medical hospital admission, and the prevalence of undiagnosed COPD in the community is high. The impact of undiagnosed COPD on presentation to secondary care services is not currently known. We therefore set out to characterise patients at first admission with an acute exacerbation of COPD, and to identify potential areas for improvement in earlier diagnosis and further management. A retrospective case review of patients first admitted to a district teaching hospital with an acute exacerbation of COPD over a 1-year period was carried out. Forty-one patients with a first admission with an acute exacerbation of COPD were identified, 14 (34%) of whom had not been previously diagnosed and were diagnosed with COPD as a result of the admission. At presentation, this group of patients had severe disease, with mean (SD) FEV(1) 1.02 (0.32) L, and a respiratory acidosis in eight (20%) patients, even though this was their first admission for an acute exacerbation of COPD. Missed potential opportunities to intervene in community and inpatient management were identified, including earlier diagnosis, pre hospital corticosteroid therapy, inpatient respiratory team input, provision of smoking cessation advice and consideration of pulmonary rehabilitation. Patients with a first hospital admission with an acute exacerbation of COPD frequently have severe disease at presentation. Despite having severe disease, a diagnosis of COPD had not been made in the community prior to admission in one-third of patients. Future work should be directed at earlier identification of patients who are symptomatic from COPD and ensuring that the interventions of proven benefit in COPD are systematically offered to patients in both primary and secondary care. PMID- 20299539 TI - "Water leakage" in an oxygenator; a suspected unexpected phenomenon. PMID- 20299540 TI - Interleukin-1 family member 9 stimulates chemokine production and neutrophil influx in mouse lungs. AB - Interleukin-1 (IL-1) is a proinflammatory cytokine that signals through the Type I IL-1 receptor (IL-1RI). Novel IL-1-like cytokines were recently identified. Their functions in lung disease remain unclear. Interleukin-1 family member-9 (IL 1F9) is one such IL-1-like cytokine, expressed in the lungs of humans and mice. IL-1F9 signals through IL-1 receptor-related protein 2 (IL-1Rrp2/IL-1RL2), which is distinct from IL-1RI. We sought to determine if IL-1F9 acts as a proinflammatory cytokine in lung disease. IL-1F9 protein was increased in lung homogenates of house dust mite-challenged A/J mice compared with controls, and expression was seen in airway epithelial cells. The intratracheal administration of recombinant mouse IL-1F9 increased airway hyperresponsiveness and induced neutrophil influx and mucus production, but not eosinophilic infiltration in the lungs of mice. In addition, IL-1alpha protein levels in bronchoalveolar lavage fluid, chemokines, and chemokine-receptor mRNA expression in the lungs were increased after the instillation of intratracheal IL-1F9. Consistent with these changes, NF-kappaB transcription factor activity was increased in the lungs of mice challenged with IL-1F9 and in a macrophage cell line treated with IL-1F9. These data suggest that IL-1F9 is upregulated during inflammation, and acts as a proinflammatory cytokine in the lungs. PMID- 20299541 TI - Editorial for PEDS special issue on antibodies. PMID- 20299542 TI - SEEDbodies: fusion proteins based on strand-exchange engineered domain (SEED) CH3 heterodimers in an Fc analogue platform for asymmetric binders or immunofusions and bispecific antibodies. AB - Bispecific antibodies and asymmetric Fc fusion proteins offer opportunities for important advances in therapeutics. Bivalent IgG depends upon in vivo dimerization of its heavy chains, mediated by homodimeric association of its C(H)3 domains. We have developed a heterodimeric Fc platform that supports the design of bispecific and asymmetric fusion proteins by devising strand-exchange engineered domain (SEED) C(H)3 heterodimers. These derivatives of human IgG and IgA C(H)3 domains create complementary human SEED C(H)3 heterodimers that are composed of alternating segments of human IgA and IgG C(H)3 sequences. The resulting pair of SEED C(H)3 domains preferentially associates to form heterodimers when expressed in mammalian cells. SEEDbody (Sb) fusion proteins consist of [IgG1 hinge]-C(H)2-[SEED C(H)3], that may be genetically linked to one or more fusion partners. This investigation reports on the generation of mono-Fab Sb and Sb-IL2 monocytokine as models. They were expressed at high levels in NS/0 cells, purified on recombinant protein A resin and were well-behaved in solution. When administered intravenously to mice, Sb pharmacokinetics exhibited the long serum half-life extensions typical of comparable Fc-containing immunofusion and IgG1 controls. PMID- 20299545 TI - Surgical repair of meniscal tears with concomitant anterior cruciate ligament reconstruction in patients 18 years and younger. AB - BACKGROUND: There are sparse data available regarding outcome of meniscal repair performed at the time of ACL reconstruction in the pediatric and adolescent population. PURPOSE: To review the results of meniscal repair performed at the time of ACL reconstruction in pediatric and adolescent patients. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: The records of all patients age 18 years or younger who underwent meniscal repair at the time of ACL reconstruction between 1990 and 2005 were reviewed. Ninety-nine patients (56 female, 43 male) with an average age of 16 years (range, 13-18) were included. Average injury to surgery interval was 107 days (range, 2-1109). Clinical outcomes were assessed at a mean of 8 years postoperatively (range, 2-19). A multivariate model was used to compare this cohort with a previously published cohort of patients with isolated meniscal tears. RESULTS: The clinical success rate of meniscal repair was 84% for simple tears, 59% for displaced bucket-handle tears, and 57% for complex tears (74% overall). Twenty-six menisci (26% overall) failed repair and 25 patients underwent repeat arthroscopic surgery (19 partial meniscectomies, 6 re-repairs). The average Tegner and International Knee Documentation Committee scores were 6.2 (range, 2-10) and 90.3 (range, 52-100), respectively. Risk factors for failure included complex and bucket-handle tear (P = .01), medial meniscal tears (P = .03), and skeletal immaturity (P = .01). Compared with isolated meniscal repairs in a similar pediatric and adolescent population, complex tears repaired in combination with ACL reconstruction did significantly better (57% vs 13%; P = .004). CONCLUSION: Clinically successful repair of meniscal tears treated at the time of ACL reconstruction in patients 18 years or younger depends on tear type, with complex and bucket-handle tears being negative prognostic factors. Complex tears have a higher rate of clinical success when repaired at the time of ACL reconstruction versus when repaired in isolation. PMID- 20299543 TI - Genome wide analyses reveal little evidence for adaptive evolution in many plant species. AB - The relative contribution of advantageous and neutral mutations to the evolutionary process is a central problem in evolutionary biology. Current estimates suggest that whereas Drosophila, mice, and bacteria have undergone extensive adaptive evolution, hominids show little or no evidence of adaptive evolution in protein-coding sequences. This may be a consequence of differences in effective population size. To study the matter further, we have investigated whether plants show evidence of adaptive evolution using an extension of the McDonald-Kreitman test that explicitly models slightly deleterious mutations by estimating the distribution of fitness effects of new mutations. We apply this method to data from nine pairs of species. Altogether more than 2,400 loci with an average length of approximately 280 nucleotides were analyzed. We observe very similar results in all species; we find little evidence of adaptive amino acid substitution in any comparison except sunflowers. This may be because many plant species have modest effective population sizes. PMID- 20299544 TI - Relationship between low levels of high-density lipoprotein cholesterol and dementia in the elderly. The InChianti study. AB - BACKGROUND: To evaluate the association between plasma lipid fractions and the prevalence of dementia in a large sample of Italian older individuals. METHODS: A total of 1051 older community-dwelling individuals (age >/=65 years), enrolled in the InChianti study, were included. Diagnosis of dementia was established at baseline and at the 3-year follow-up using Diagnostic and Statistical Manual of Mental Disorder (Fourth Edition) criteria. Plasma lipids were measured by standardized methods at baseline and after 3 years. RESULTS: At baseline, 61 individuals (5.8%) were affected by dementia. Demented individuals showed significantly lower total cholesterol (TC), nonhigh-density lipoprotein cholesterol, and high-density lipoprotein cholesterol (HDL-C) levels compared with controls; no differences were found in triglycerides (TG) and lipoprotein (a) levels. Of the 819 subjects reevaluated at the 3-year follow-up, 81 (9.9%) received a new diagnosis of dementia. Again, demented subjects were characterized by significantly lower TC, non-HDL-C, and HDL-C levels compared with controls, thus confirming the baseline findings. At multivariate logistic regression analysis, HDL-C levels (odds ratio: 0.96, 95% confidence interval: 0.93-0.99), but not TG and non-HDL-C, were associated with dementia independent of important confounders including age, gender, apo E phenotype, stroke, weight loss, interleukin 6 levels, and ankle-brachial index. CONCLUSIONS: Among community dwelling older people, individuals affected by dementia showed significantly lower TC, non-HDL-C, and HDL-C levels; however, at multivariate analysis, only HDL-C was associated with dementia. Our results suggest the existence of an independent relationship between dementia and low HDL-C levels. PMID- 20299546 TI - 2,3,7,8-tetrachlorodibenzo-p-dioxin counteracts the p53 response to a genotoxicant by upregulating expression of the metastasis marker agr2 in the hepatocarcinoma cell line HepG2. AB - 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is an environmental pollutant that binds the aryl hydrocarbon receptor (AhR), a transcription factor that triggers various biological responses. In this study, we show that TCDD treatment counteracts the p53 activation (phosphorylation and acetylation) elicited by a genotoxic compound, etoposide, in the human hepatocarcinoma cell line HepG2 and we delineated the mechanisms of this interaction. Using small interfering RNA knockdown experiments, we found that the newly described metastasis marker, anterior gradient-2 (AGR2), is involved in this effect. Both AGR2 messenger RNA (mRNA) and protein levels were increased (sixfold and fourfold, respectively) by TCDD treatment, and this effect was mediated by the AhR receptor. The half-life of AGR2 mRNA was unchanged by TCDD treatment. Analysis of the promoter of the AGR2 gene revealed three putative xenobiotic-responsive elements (XREs) in the proximal 3.5-kb promoter. Transient transfection of HepG2 cells by the Gaussia luciferase reporter gene driven by various deleted and mutated fragments of the promoter indicated that only the most proximal XRE was active. Binding of the AhR to the endogenous AGR2 promoter was also triggered by TCDD treatment. These results suggest that AhR ligands such as TCDD might contribute to tumor progression by inhibiting p53 regulation (phosphorylation and acetylation) triggered by genotoxicants via the increased expression of the metastasis marker AGR2. PMID- 20299547 TI - Embryotoxic and teratogenic effects of the combination of bisphenol A and genistein on in vitro cultured postimplantation rat embryos. AB - The potential teratogenic effects and fetal toxicity of environmental estrogenic endocrine disruptors have become a great concern in recent years, and they have yet to be fully characterized. In the present study, the teratogenic effects of bisphenol A (BPA) and genistein (GEN) on rat embryos during their critical period of organogenesis were investigated using a whole-embryo culture experiment. The combined exposure effects of BPA and GEN were explored using a 4 x 4 full factorial design. Both BPA and GEN produced concentration-dependent inhibition of embryonic development, beginning at 32.0 and 10.0 microg/ml, respectively. Full factorial and isobologram analyses revealed a significant synergistic interaction between BPA and GEN for most end points (12 out of 20 tested), as indicated by the enhanced developmental toxicity of BPA after coexposure with different dose levels of GEN. In particular, serious malformations and a higher abnormal frequency of the central nervous system were induced by the combination of BPA and GEN. Our findings suggest that GEN may be embryotoxic and teratogenic to humans. BPA alone may not be a potential teratogen, but these two estrogenic chemicals have a synergistic effect on embryonic development when present together during the critical period of major organ formation. The current findings suggest that pregnant women should not take soy supplements, but more studies are necessary to provide a conclusive recommendation. PMID- 20299548 TI - Variation in transcription factor binding among humans. AB - Differences in gene expression may play a major role in speciation and phenotypic diversity. We examined genome-wide differences in transcription factor (TF) binding in several humans and a single chimpanzee by using chromatin immunoprecipitation followed by sequencing. The binding sites of RNA polymerase II (PolII) and a key regulator of immune responses, nuclear factor kappaB (p65), were mapped in 10 lymphoblastoid cell lines, and 25 and 7.5% of the respective binding regions were found to differ between individuals. Binding differences were frequently associated with single-nucleotide polymorphisms and genomic structural variants, and these differences were often correlated with differences in gene expression, suggesting functional consequences of binding variation. Furthermore, comparing PolII binding between humans and chimpanzee suggests extensive divergence in TF binding. Our results indicate that many differences in individuals and species occur at the level of TF binding, and they provide insight into the genetic events responsible for these differences. PMID- 20299549 TI - Heritable individual-specific and allele-specific chromatin signatures in humans. AB - The extent to which variation in chromatin structure and transcription factor binding may influence gene expression, and thus underlie or contribute to variation in phenotype, is unknown. To address this question, we cataloged both individual-to-individual variation and differences between homologous chromosomes within the same individual (allele-specific variation) in chromatin structure and transcription factor binding in lymphoblastoid cells derived from individuals of geographically diverse ancestry. Ten percent of active chromatin sites were individual-specific; a similar proportion were allele-specific. Both individual specific and allele-specific sites were commonly transmitted from parent to child, which suggests that they are heritable features of the human genome. Our study shows that heritable chromatin status and transcription factor binding differ as a result of genetic variation and may underlie phenotypic variation in humans. PMID- 20299550 TI - Resolving mechanisms of competitive fertilization success in Drosophila melanogaster. AB - Our understanding of postcopulatory sexual selection has been constrained by an inability to discriminate competing sperm of different males, coupled with challenges of directly observing live sperm inside the female reproductive tract. Real-time and spatiotemporal analyses of sperm movement, storage, and use within female Drosophila melanogaster inseminated by two transgenic males with, respectively, green and red sperm heads allowed us to unambiguously discriminate among hypothesized mechanisms underlying sperm precedence, including physical displacement and incapacitation of "resident" sperm by second males, female ejection of sperm, and biased use of competing sperm for fertilization. We find that competitive male fertilization success derives from a multivariate process involving ejaculate-female and ejaculate-ejaculate interactions, as well as complex sperm behavior in vivo. PMID- 20299551 TI - Three-dimensional invisibility cloak at optical wavelengths. AB - We have designed and realized a three-dimensional invisibility-cloaking structure operating at optical wavelengths based on transformation optics. Our blueprint uses a woodpile photonic crystal with a tailored polymer filling fraction to hide a bump in a gold reflector. We fabricated structures and controls by direct laser writing and characterized them by simultaneous high-numerical-aperture, far-field optical microscopy and spectroscopy. A cloaking operation with a large bandwidth of unpolarized light from 1.4 to 2.7 micrometers in wavelength is demonstrated for viewing angles up to 60 degrees. PMID- 20299554 TI - Fusion. Budget red tape in Europe brings new delay to ITER. PMID- 20299553 TI - Science-based health care. PMID- 20299552 TI - Functional hierarchy and reversibility within the murine spermatogenic stem cell compartment. AB - Stem cells support tissue maintenance by balancing self-renewal and differentiation. In mice, it is believed that a homogeneous stem cell population of single spermatogonia supports spermatogenesis, and that differentiation, which is accompanied by the formation of connected cells (cysts) of increasing length, is linear and nonreversible. We evaluated this model with the use of lineage analysis and live imaging, and found that this putative stem cell population is not homogeneous. Instead, the stem cell pool that supports steady-state spermatogenesis is contained within a subpopulation of single spermatogonia. We also found that cysts are not committed to differentiation and appear to recover stem cell potential by fragmentation, and that the fate of individual spermatogonial populations was markedly altered during regeneration after damage. Thus, there are multiple and reversible paths from stem cells to differentiation, and these may also occur in other systems. PMID- 20299555 TI - Anthrax investigation. Silicon mystery endures in solved anthrax case. PMID- 20299556 TI - Psychiatry. Beyond DSM: seeking a brain-based classification of mental illness. PMID- 20299557 TI - U.S. science policy. MIT engineering dean tapped to head NSF. PMID- 20299558 TI - National Science Foundation. Budget shortfall could derail plans for underground lab. PMID- 20299559 TI - India. Hardy cotton-munching pests are latest blow to GM crops. PMID- 20299560 TI - 2010 budget. Fresh momentum for China's science juggernaut. PMID- 20299561 TI - 2010 budget. China amasses war chest to confront its environmental nightmares. PMID- 20299563 TI - Research funding. Polish science reforms bring fear and hope. PMID- 20299565 TI - Evolution. Male rivalry extends to sperm in female reproductive tract. PMID- 20299566 TI - Climate change. The Nile Delta's sinking future. PMID- 20299567 TI - Lunar and Planetary Science Conference. Coaxing out another taste of the sun. PMID- 20299568 TI - Lunar and Planetary Science Conference. Lucky glimpses of a weirdly wetter moon. PMID- 20299570 TI - Lunar and Planetary Science Conference. Spirit is willing, though weak. PMID- 20299569 TI - Lunar and Planetary Science Conference. Snapshots from the meeting. PMID- 20299571 TI - Chilean scientists rally after quake. PMID- 20299573 TI - Unlocking the door to better cybersecurity. PMID- 20299574 TI - Planning for biodiversity in future climates. PMID- 20299575 TI - Salmon swimming against multiple threats. PMID- 20299576 TI - Is the message from Athens being heard? PMID- 20299578 TI - Ecology. China, India, and the environment. PMID- 20299579 TI - Chemistry. Setting the trap for reactive resonances. PMID- 20299580 TI - Plant science. Phenology under global warming. PMID- 20299581 TI - Applied physics. Controlling turbulence. PMID- 20299582 TI - Neuroscience. AMPA receptors--another twist? PMID- 20299583 TI - Physics. Toward organic all-optical switching. PMID- 20299584 TI - Behavior. Fairness in modern society. PMID- 20299585 TI - Materials science. Expanding the repertoire of shape memory alloys. PMID- 20299586 TI - An evolving view of Saturn's dynamic rings. AB - We review our understanding of Saturn's rings after nearly 6 years of observations by the Cassini spacecraft. Saturn's rings are composed mostly of water ice but also contain an undetermined reddish contaminant. The rings exhibit a range of structure across many spatial scales; some of this involves the interplay of the fluid nature and the self-gravity of innumerable orbiting centimeter- to meter-sized particles, and the effects of several peripheral and embedded moonlets, but much remains unexplained. A few aspects of ring structure change on time scales as short as days. It remains unclear whether the vigorous evolutionary processes to which the rings are subject imply a much younger age than that of the solar system. Processes on view at Saturn have parallels in circumstellar disks. PMID- 20299587 TI - Saturn: atmosphere, ionosphere, and magnetosphere. AB - The Cassini spacecraft has been in orbit around Saturn since 30 June 2004, yielding a wealth of data about the Saturn system. This review focuses on the atmosphere and magnetosphere and briefly outlines the state of our knowledge after the Cassini prime mission. The mission has addressed a host of fundamental questions: What processes control the physics, chemistry, and dynamics of the atmosphere? Where does the magnetospheric plasma come from? What are the physical processes coupling the ionosphere and magnetosphere? And, what are the rotation rates of Saturn's atmosphere and magnetosphere? PMID- 20299588 TI - Markets, religion, community size, and the evolution of fairness and punishment. AB - Large-scale societies in which strangers regularly engage in mutually beneficial transactions are puzzling. The evolutionary mechanisms associated with kinship and reciprocity, which underpin much of primate sociality, do not readily extend to large unrelated groups. Theory suggests that the evolution of such societies may have required norms and institutions that sustain fairness in ephemeral exchanges. If that is true, then engagement in larger-scale institutions, such as markets and world religions, should be associated with greater fairness, and larger communities should punish unfairness more. Using three behavioral experiments administered across 15 diverse populations, we show that market integration (measured as the percentage of purchased calories) positively covaries with fairness while community size positively covaries with punishment. Participation in a world religion is associated with fairness, although not across all measures. These results suggest that modern prosociality is not solely the product of an innate psychology, but also reflects norms and institutions that have emerged over the course of human history. PMID- 20299589 TI - Ferrous polycrystalline shape-memory alloy showing huge superelasticity. AB - Shape-memory alloys, such as Ni-Ti and Cu-Zn-Al, show a large reversible strain of more than several percent due to superelasticity. In particular, the Ni-Ti based alloy, which exhibits some ductility and excellent superelastic strain, is the only superelastic material available for practical applications at present. We herein describe a ferrous polycrystalline, high-strength, shape-memory alloy exhibiting a superelastic strain of more than 13%, with a tensile strength above 1 gigapascal, which is almost twice the maximum superelastic strain obtained in the Ni-Ti alloys. Furthermore, this ferrous alloy has a very large damping capacity and exhibits a large reversible change in magnetization during loading and unloading. This ferrous shape-memory alloy has great potential as a high damping and sensor material. PMID- 20299590 TI - Eliminating turbulence in spatially intermittent flows. AB - Flows through pipes and channels are the most common means to transport fluids in practical applications and equally occur in numerous natural systems. In general, the transfer of fluids is energetically far more efficient if the motion is smooth and laminar because the friction losses are lower. However, even at moderate velocities pipe and channel flows are sensitive to minute disturbances, and in practice most flows are turbulent. Investigating the motion and spatial distribution of vortices, we uncovered an amplification mechanism that constantly feeds energy from the mean shear into turbulent eddies. At intermediate flow rates, a simple control mechanism suffices to intercept this energy transfer by reducing inflection points in the velocity profile. When activated, an immediate collapse of turbulence is observed, and the flow relaminarizes. PMID- 20299591 TI - Microcavity laser oscillating in a circuit-based resonator. AB - Lasers based on microcavities are extremely attractive for their compactness, low power dissipation, and potential for ultrafast modulation speed. We describe an ultrasmall laser based on a subwavelength electronic inductor-capacitor (LC) resonant circuit that allows for extreme confinement of the electric field. This electrically injected laser operates at a frequency of 1.5 terahertz, and the mode volume is strongly subwavelength. The design concept of the LC resonator can be extended from the terahertz range to higher frequencies and also applied to detectors and modulators. PMID- 20299592 TI - The climatic signature of incised river meanders. AB - Climate controls landscape evolution, but quantitative signatures of climatic drivers have yet to be found in topography on a broad scale. Here we describe how a topographic signature of typhoon rainfall is recorded in the meandering of incising mountain rivers in the western North Pacific. Spatially averaged river sinuosity generated from digital elevation data peaks in the typhoon-dominated subtropics, where extreme rainfall and flood events are common, and decreases toward the equatorial tropics and mid-latitudes, where such extremes are rare. Once climatic trends are removed, the primary control on sinuosity is rock weakness. Our results indicate that the weakness of bedrock channel walls and their weakening by heavy rainfall together modulate rates of meander propagation and sinuosity development in incising rivers. PMID- 20299593 TI - Transition-state spectroscopy of partial wave resonances in the F + HD reaction. AB - Partial wave resonances, quasi-bound resonance states with well-defined rotation in the transition state region of a chemical reaction, play a governing role in reaction dynamics but have eluded direct experimental characterization. Here, we report the observation of individual partial wave resolved resonances in the F + HD --> HF + D reaction by measuring the collision energy-dependent, angle- and state-resolved differential cross section with extremely high resolution, providing a spectroscopic probe to the transition state of F + HD --> HF + D. The agreement of the data with the high-level theoretical calculations confirms the sensitivity of this probe to the subtle quantum mechanical factors guiding this benchmark reaction. PMID- 20299594 TI - Mechanosensitive self-replication driven by self-organization. AB - Self-replicating molecules are likely to have played an important role in the origin of life, and a small number of fully synthetic self-replicators have already been described. Yet it remains an open question which factors most effectively bias the replication toward the far-from-equilibrium distributions characterizing even simple organisms. We report here two self-replicating peptide derived macrocycles that emerge from a small dynamic combinatorial library and compete for a common feedstock. Replication is driven by nanostructure formation, resulting from the assembly of the peptides into fibers held together by beta sheets. Which of the two replicators becomes dominant is influenced by whether the sample is shaken or stirred. These results establish that mechanical forces can act as a selection pressure in the competition between replicators and can determine the outcome of a covalent synthesis. PMID- 20299595 TI - Seminal fluid mediates ejaculate competition in social insects. AB - Queens of ants and bees normally obtain a lifetime supply of sperm on a single day of sexual activity, and sperm competition is expected to occur in lineages where queens receive sperm from multiple males. We compared singly mated (monandrous) and multiply mated (polyandrous) sister groups of ants and bees and show that seminal fluid of polyandrous species has a more positive effect on the survival of a male's own sperm than on other males' sperm. This difference was not observed in the monandrous species, suggesting that incapacitation of competing sperm may have independently evolved in both bees and ants. In Atta leafcutter ants, the negative effect of the seminal fluid of other males was negated by secretion from the queen sperm-storage organ, suggesting that queens may control ejaculate competition after sperm storage. PMID- 20299596 TI - A critical role for alpha4betadelta GABAA receptors in shaping learning deficits at puberty in mice. AB - The onset of puberty defines a developmental stage when some learning processes are diminished, but the mechanism for this deficit remains unknown. We found that, at puberty, expression of inhibitory alpha4betadelta gamma-aminobutyric acid type A (GABAA) receptors (GABAR) increases perisynaptic to excitatory synapses in CA1 hippocampus. Shunting inhibition via these receptors reduced N methyl-D-aspartate receptor activation, impairing induction of long-term potentiation (LTP). Pubertal mice also failed to learn a hippocampal, LTP dependent spatial task that was easily acquired by delta-/- mice. However, the stress steroid THP (3alphaOH-5alpha[beta]-pregnan-20-one), which reduces tonic inhibition at puberty, facilitated learning. Thus, the emergence of alpha4betadelta GABARs at puberty impairs learning, an effect that can be reversed by a stress steroid. PMID- 20299599 TI - Probiotic bacteria and intestinal epithelial barrier function. AB - The intestinal tract is a diverse microenvironment where more than 500 species of bacteria thrive. A single layer of epithelium is all that separates these commensal microorganisms and pathogens from the underlying immune cells, and thus epithelial barrier function is a key component in the arsenal of defense mechanisms required to prevent infection and inflammation. The epithelial barrier consists of a dense mucous layer containing secretory IgA and antimicrobial peptides as well as dynamic junctional complexes that regulate permeability between cells. Probiotics are live microorganisms that confer benefit to the host and that have been suggested to ameliorate or prevent diseases including antibiotic-associated diarrhea, irritable bowel syndrome, and inflammatory bowel disease. Probiotics likely function through enhancement of barrier function, immunomodulation, and competitive adherence to the mucus and epithelium. This review summarizes the evidence about effects of the many available probiotics with an emphasis on intestinal barrier function and the mechanisms affected by probiotics. PMID- 20299597 TI - Circadian gating of the cell cycle revealed in single cyanobacterial cells. AB - Although major progress has been made in uncovering the machinery that underlies individual biological clocks, much less is known about how multiple clocks coordinate their oscillations. We simultaneously tracked cell division events and circadian phases of individual cells of the cyanobacterium Synechococcus elongatus and fit the data to a model to determine when cell cycle progression slows as a function of circadian and cell cycle phases. We infer that cell cycle progression in cyanobacteria slows during a specific circadian interval but is uniform across cell cycle phases. Our model is applicable to the quantification of the coupling between biological oscillators in other organisms. PMID- 20299600 TI - Novel anti-inflammatory functions for endothelial and myeloid cyclooxygenase-2 in a new mouse model of Crohn's disease. AB - Cyclooxygenase-2 (COX-2) is an important regulator of inflammation implicated in the development of a variety of diseases, including inflammatory bowel disease (IBD). However, the regulation of intestinal inflammation by COX-2 is poorly understood. We previously reported that COX-2(-/-) mice fed a cholate-containing high-fat (CCHF) diet had high mortality of unknown mechanisms attributable to severe intestinal inflammation in the ileo-ceco-colic junction that presented characteristics similar to Crohn's disease (CD). To further characterize the role of COX-2 in intestinal inflammation, we established cell-specific conditional COX 2(-/-) mice. Endothelial cell-specific (COX-2(-E/-E)) and myeloid cell-specific (COX-2(-M/-M)) COX-2(-/-) mice, but not wild-type mice, on the CCHF diet developed localized CD-like pathology at the ileo-ceco-colic junction that was associated with cellular infiltration, increased expression of myeloperoxidase and IL-5, and decreased IL-10 expression. The CD-like pathology in COX-2(-E/-E) mice was also accompanied by increased expression of cytokines (IL-6, TNF-alpha, and INF-gamma), compared with wild-type mice and COX-2(-M/-M) mice. In contrast, the ileo-ceco-colic inflammation in COX-2(-M/-M) mice was associated with more pronounced infiltration of granulocytes and macrophages than COX-2(-E/-E) mice. COX-2(-ME/-ME) (COX-2(-M/-M) x COX-2(-E/-E)) mice on the CCHF diet developed CD like pathology in the ileo-ceco-colic junction reminiscent of total COX-2(-/-) mice on CCHF diet and wild-type mice on CCHF diet treated with COX-2 inhibitor, celecoxib. The pathology of diet-mediated ileo-ceco-colic inflammation in COX-2( /-) mice offers an excellent model system to elucidate the protective roles of endothelial and myeloid COX-2 and the molecular pathogenesis of CD. PMID- 20299601 TI - Exploring the interplay of barrier function and leukocyte recruitment in intestinal inflammation by targeting fucosyltransferase VII and trefoil factor 3. AB - Intestinal mucosal integrity is dependent on epithelial function and a regulated immune response to injury. Fucosyltransferase VII (Fuc-TVII) is an essential enzyme required for the expression of the functional ligand for E- and P selectin. Trefoil factor 3 (TFF3) is involved in both protecting the intestinal epithelium against injury as well as aiding in wound repair following injury. The aim of the present study was to assess the interplay between barrier function and leukocyte recruitment in intestinal inflammation. More specifically, we aimed to examine how targeted disruption of Fuc-TVII either in wild-type or TFF3(-/-) mice would alter their susceptibility to colonic injury. TFF3 and Fuc-TVII double knockout mice (TFF3/Fuc-TVII(-/-) mice) were generated by mating TFF3(-/-) and Fuc-TVII(-/-) mice. Colitis was induced by administration of dextran sodium sulfate (DSS) (2.5% wt/vol) in the drinking water. Changes in baseline body weight, diarrhea, and fecal blood were assessed daily. Upon euthanasia, extents of colonic inflammation were assessed macroscopically, microscopically, and through quantification of myeloperoxidase (MPO) activity. Colonic lymphocyte subpopulations were assessed at 6 days after administration of DSS by flow cytometry and immunohistochemistry. No baseline intestinal inflammation was found in TFF3/Fuc-TVII(-/-), TFF3(-/-), Fuc-TVII(-/-), or wild-type mice. Loss of Fuc TVII resulted in a reduction in disease severity whereas TFF3(-/-) mice were markedly more susceptible to DSS-induced colitis. Remarkably, the loss of Fuc TVII in TFF3(-/-) mice markedly decreased the severity of DSS-induced colitis as evidenced by reduced weight loss, diarrhea, decreased colonic MPO levels and improved survival. Furthermore, the loss of TFF3 resulted in increased severity of spontaneous colitis in IL-2/beta-microglobulin-deficient mice. These studies highlight the importance of the interplay between factors involved in the innate immune response, mucosal barrier function, and genes involved in regulating leukocyte recruitment and other aspects of the immune response. PMID- 20299602 TI - Schlafen 3 induction by cyclic strain regulates intestinal epithelial differentiation. AB - The intestinal epithelium is subjected to repetitive deformation during normal gut function by peristalsis and villous motility. In vitro, cyclic strain promotes intestinal epithelial proliferation and induces an absorptive phenotype characterized by increased dipeptidyl dipeptidase (DPPIV) expression. Schlafen 3 is a novel gene recently associated with cellular differentiation. We sought to evaluate whether Schlafen 3 mediates the effects of strain on the differentiation of intestinal epithelial cell (IEC)-6 in the absence or presence of cyclic strain. Strain increased Schlafen 3 mRNA and protein. In cells transfected with a control-nontargeting siRNA, strain increased DPPIV-specific activity. However, Schlafen 3 reduction by siRNA decreased basal DPPIV and prevented any stimulation of DPPIV activity by strain. Schlafen 3 reduction also prevented DPPIV induction by sodium butyrate (1 mM) or transforming growth factor (TGF)-beta (0.1 ng/ml), two unrelated differentiating stimuli. However, Schlafen-3 reduction by siRNA did not prevent the mitogenic effect of strain or that of EGF. Blocking Src and phosphatidyl inositol (PI3)-kinase prevented strain induction of Schlafen 3, but Schlafen 3 induction required activation of p38 but not ERK. These results suggest that cyclic strain induces an absorptive phenotype characterized by increased DPPIV activity via Src-, p38-, and PI3-kinase-dependent induction of Schlafen 3 in rat IEC-6 cells on collagen, whereas Schlafen 3 may also be a key factor in the induction of intestinal epithelial differentiation by other stimuli such as sodium butyrate or TGF-beta. The induction of Schlafen 3 or its human homologs may modulate intestinal epithelial differentiation and preserve the gut mucosa during normal gut function. PMID- 20299603 TI - Modulatory effect of curcumin on survival of irradiated human intestinal microvascular endothelial cells: role of Akt/mTOR and NF-{kappa}B. AB - Radiation therapy is an essential modality in the treatment of colorectal cancers. Radiation exerts an antiangiogenic effect on tumors, inhibiting endothelial proliferation and survival in the tumor microvasculature. However, damage from low levels of irradiation can induce a paradoxical effect, stimulating survival in endothelial cells. We used human intestinal microvascular endothelial cells (HIMEC) to define effects of radiation on these gut-specific endothelial cells. Low-level irradiation (1-5 Gy) activates NF-kappaB and the phosphatidylinositol 3-kinase (PI3K)/Akt pathway, which is involved in cell cycle reentry and cell survival in HIMEC. A downstream target of PI3K/Akt is mammalian target of rapamycin (mTOR), which contributes to endothelial proliferation and angiogenesis. The aim of this study was to investigate the signaling molecules involved in the radiosensitizing effects of curcumin on HIMEC subjected to low levels of irradiation. We have demonstrated that exposure of HIMEC to low levels of irradiation induced Akt and mTOR phosphorylation, which was attenuated by curcumin, rapamycin, LY294002, and mTOR small interference RNA (siRNA). Activation of NF-kappaB by low levels of irradiation was inhibited by curcumin, SN-50, and mTOR siRNA. Curcumin also induced apoptosis by induction of caspase-3 cleavage in irradiated HIMEC. In conclusion, curcumin significantly inhibited NF kappaB and attenuated the effect of irradiation-induced prosurvival signaling through the PI3K/Akt/mTOR and NF-kappaB pathways in these gut-specific endothelial cells. Curcumin may be a potential radiosensitizing agent for enhanced antiangiogenic effect in colorectal cancer radiation therapy. PMID- 20299605 TI - Decreased phospho-Akt signaling in a mouse model of total parenteral nutrition: a potential mechanism for the development of intestinal mucosal atrophy. AB - Total parenteral nutrition (TPN) leads to a decline in phosphatidylinositol 3 kinase (PI3K)/phospho-Akt (p-Akt) activity, affecting downstream signaling, reducing epithelial cell (EC) proliferation, and contributing to intestinal mucosal atrophy. We hypothesized that promoting Akt activity would prevent these changes. We used a novel Akt-activating peptide, TCL1 (a head-to-tail dimer of the Akt-binding domain of T-cell lymphoma-1), or an inactive mutant sequence TCL1G conjugated to a transactivator of transcription peptide sequence to promote intracellular uptake. Four groups of mice were studied, enteral nutrition group (control), control mice given a functioning TCL1 (control + TCL1), TPN mice given TCL1G (control peptide, TPN + TCL1G); and TPN mice given TCL1. TPN mice given TCL1G showed a significant decrease in jejunal EC p-Akt (Ser473 and Thr308) abundance, whereas TPN + TCL1 mice showed increased p-Akt (Ser473) abundance. Phosphorylation of beta-catenin and glycogen synthase kinase-3beta (downstream targets of Akt signaling) were also decreased in the TPN + TCL1G group and completely prevented in the TPN + TCL1 group. Use of TCL1 nearly completely prevented the decline in EC proliferation seen in the TPN + TCL1G group, as well as partly returned EC apoptosis levels close to controls. The mammalian target of rapamycin pathway demonstrated a similar reduction in activity in the TPN + TCL1G group that was significantly prevented in the TPN + TCL1 group. These results support a significant loss of PI3K/p-Akt signaling upon replacing enteral nutrition with TPN, and prevention of this loss demonstrates the key importance of PI3K/p-Akt signaling in maintaining gut integrity including EC proliferation and reduction in apoptosis. PMID- 20299606 TI - The endothelial mineralocorticoid receptor regulates vasoconstrictor tone and blood pressure. AB - Pathophysiological aldosterone (aldo)/mineralocorticoid receptor (MR) signaling has significant effects on the cardiovascular system, resulting in hypertension and cardiovascular remodeling; however, the specific contribution of the vascular MR to blood pressure regulation remains to be established. To address this question, we generated a mouse model with conditional overexpression of the MR in endothelial cells (MR-EC). In basal conditions, MR-EC mice developed moderate hypertension that could be reversed by canrenoate, a pharmacological MR antagonist. MR-EC mice presented increased contractile response of resistance arteries to vasoconstrictors (phenylephrine, thromboxane A(2) analog, angiotensin II, and endothelin 1) in the absence of vascular morphological alterations. The acute blood pressure response to angiotensin II or endothelin 1 infusion was increased in MR-EC mice compared with that in littermate controls. These observations demonstrate that enhanced MR activation in the endothelium generates an increase in blood pressure, independent of stimulation of renal tubular Na(+) transport by aldo/MR or direct activation of smooth muscle MR and establish one mechanism by which endothelial MR activation per se may contribute to impaired vascular reactivity. PMID- 20299607 TI - Randomized, double-blind, multicenter, placebo-controlled study evaluating the effect of aldosterone antagonism with eplerenone on ventricular remodeling in patients with mild-to-moderate heart failure and left ventricular systolic dysfunction. AB - BACKGROUND: Aldosterone antagonism has been studied in patients with advanced heart failure (HF) and also in patients with post-myocardial infarction and left ventricular (LV) dysfunction with HF symptoms. Few data are available on effects of aldosterone antagonism in patients with mild-to-moderate HF. METHODS AND RESULTS: In a multicenter, randomized, double-blind, placebo-controlled study in patients with mild-to-moderate HF and LV systolic dysfunction, patients with New York Heart Association class II/III HF and LV ejection fraction (EF) < or =35% were randomly assigned to receive eplerenone 50 mg/d versus placebo in addition to contemporary background therapy. Quantitative radionuclide ventriculograms to assess LV volumes and ejection fraction were performed at baseline and again after 9 months of double-blind treatment and were analyzed in a central core laboratory, blinded to treatment. The primary efficacy analysis was the between group comparison of the change in LV end-diastolic volume index. Secondary analyses examined changes in LV end-systolic volume index and ejection fraction as well as markers of collagen turnover. Of the total 226 patients enrolled, 117 were randomly assigned to receive eplerenone and 109 to receive placebo. There was high use of contemporary background therapy at baseline, with > 90% use of angiotensin-converting enzyme inhibitors and/or angiotensin receptor blockers and > 90% use of beta-blockers. Over 36 weeks of treatment, there was no apparent between-group difference in the changes in end-diastolic volume index or end systolic volume index. There was a reduction in the collagen turnover marker procollagen type I N-terminal propeptide and plasma B-type natriuretic peptide in the eplerenone group compared with placebo (P=0.01 and P=0.04, respectively). There was no change in symptom status or quality-of-life measures. CONCLUSIONS: In a clinically stable, well-treated population of patients with mild-to-moderate HF symptoms and LV dysfunction, 36 weeks of treatment of aldosterone antagonism with eplerenone at a dose of 50 mg daily had no detectable effect on parameters of LV remodeling. PMID- 20299604 TI - Inflammatory mediators in gastroesophageal reflux disease: impact on esophageal motility, fibrosis, and carcinogenesis. AB - Gastroesophageal reflux disease (GERD) is one of the most common problems in clinical practice today. It is widely believed that functional and structural abnormalities of the gastroesophageal junction as well as an abnormal exposure to gastroduodenal contents are the main contributors to its pathogenesis. Novel findings of the inflammatory process in GERD suggest a far more complex process involving multifaceted inflammatory mechanisms. This review summarizes knowledge about the expression of inflammatory mediators in GERD and their potential cellular sources and provides an integrated concept of disease pathogenesis. In addition we evaluate the contribution of inflammatory mediators to well-known complications of GERD, namely motility abnormalities, fibrosis, and carcinogenesis. Novel findings regarding the pathophysiology of esophageal inflammation should enhance our understanding of GERD and its complications and provide new treatment insights. PMID- 20299608 TI - Heat stress alters hemodynamic responses during the Valsalva maneuver. AB - The Valsalva maneuver can be used as a noninvasive index of autonomic control of blood pressure and heart rate. The purpose of this investigation was to test the hypothesis that sympathetic mediated vasoconstriction, as referenced by hemodynamic responses during late phase II (phase IIb) of the Valsalva maneuver, is inhibited during whole body heating. Seven individuals (5 men, 2 women) performed three Valsalva maneuvers (each at a 30-mmHg expiratory pressure for 15 s) during normothermia and again during whole body heating (increase sublingual temperature approximately 0.8 degrees C via water-perfused suit). Each Valsalva maneuver was separated by a minimum of 5 min. Beat-to-beat mean arterial blood pressure (MAP) and heart rate were measured during each Valsalva maneuver, and responses for each phase were averaged across the three Valsalva maneuvers for both thermal conditions. Baseline MAP was not significantly different between normothermic (88+/-11 mmHg) and heat stress (84+/-9 mmHg) conditions. The change in MAP (DeltaMAP) relative to pre-Valsalva MAP during phases IIa and IIb was significantly lower during heat stress (IIa=-20+/-8 mmHg; IIb=-13+/-7 mmHg) compared with normothermia (IIa=-1+/-15 mmHg; IIb=3+/-13 mmHg). DeltaMAP from pre Valsalva baseline during phase IV was significantly higher during heat stress (25+/-10 mmHg) compared with normothermia (8+/-9 mmHg). Counter to the proposed hypothesis, the increase in MAP from the end of phase IIa to the end of phase IIb during heat stress was not attenuated. Conversely, this increase in MAP tended to be greater during heat stress relative to normothermia (P=0.06), suggesting that sympathetic activation may be elevated during this phase of the Valsalva while heat stressed. These data show that heat stress does not attenuate this index of vasoconstrictor responsiveness during the Valsalva maneuver. PMID- 20299609 TI - Fuel selection and cycling endurance performance with ingestion of [13C]glucose: evidence for a carbohydrate dose response. AB - Endurance performance and fuel selection while ingesting glucose (15, 30, and 60 g/h) was studied in 12 cyclists during a 2-h constant-load ride [approximately 77% peak O2 uptake] followed by a 20-km time trial. Total fat and carbohydrate (CHO) oxidation and oxidation of exogenous glucose, plasma glucose, glucose released from the liver, and muscle glycogen were computed using indirect respiratory calorimetry and tracer techniques. Relative to placebo (210+/-36 W), glucose ingestion increased the time trial mean power output (%improvement, 90% confidence limits: 7.4, 1.4 to 13.4 for 15 g/h; 8.3, 1.4 to 15.2 for 30 g/h; and 10.7, 1.8 to 19.6 for 60 g/h glucose ingested; effect size=0.46). With 60 g/h glucose, mean power was 2.3, 0.4 to 4.2% higher, and 3.1, 0.5 to 5.7% higher than with 30 and 15 g/h, respectively, suggesting a relationship between the dose of glucose ingested and improvements in endurance performance. Exogenous glucose oxidation increased with ingestion rate (0.17+/-0.04, 0.33+/-0.04, and 0.52+/ 0.09 g/min for 15, 30, and 60 g/h glucose), but endogenous CHO oxidation was reduced only with 30 and 60 g/h due to the progressive inhibition of glucose released from the liver (probably related to higher plasma insulin concentration) with increasing ingestion rate without evidence for muscle glycogen sparing. Thus ingestion of glucose at low rates improved cycling time trial performance in a dose-dependent manner. This was associated with a small increase in CHO oxidation without any reduction in muscle glycogen utilization. PMID- 20299610 TI - Age and load compliance alter time to task failure for a submaximal fatiguing contraction with the lower leg. AB - The purpose of this study was to compare the time to failure and muscle activation of young and old adults for a sustained isometric submaximal contraction with the dorsiflexor muscles when the foot was restrained to a force transducer (force-control task) compared with supporting an equivalent inertial load unrestrained in the sagittal plane (position-control task). Seventeen young (23.6+/-6.5 yr) and 12 old (70.0+/-5.0 yr) adults performed the force-control and position-control tasks at 30% maximal voluntary contraction (MVC) until task failure on separate days. Despite the similar load torque for each task, time to failure was longer for the force-control than position-control task (10.4+/-4.5 vs. 8.6+/-3.4 min, P=0.03) for the young and old adults. The old adults, however, had a longer time to task failure than the young adults for both tasks (11.4+/ 4.4 vs. 8.1+/-2.1 min, P=0.01), with no interaction of age and task (P=0.83). The rate of increase in agonist and antagonist root-mean-square EMG, agonist EMG bursting activity, mean arterial pressure, and heart rate during the fatiguing contraction was greater for the position-control than force-control task for the young and old adults. The old adults had a less rapid rate of increase in EMG activity, fluctuations in motor output, and cardiovascular measures than the young adults for both tasks. Development of fatigue can be manipulated in young and old adults by providing greater support to the foot and less ankle compliance during daily and ergonomic tasks that require prolonged activation of the lower leg. Minimizing load compliance to one degree of freedom during a position control task maintained the greater fatigue resistance with age for an isometric contraction. PMID- 20299611 TI - Is interindividual variability of EMG patterns in trained cyclists related to different muscle synergies? AB - Our aim was to determine whether muscle synergies are similar across trained cyclists (and thus whether the same locomotor strategies for pedaling are used), despite interindividual variability of individual EMG patterns. Nine trained cyclists were tested during a constant-load pedaling exercise performed at 80% of maximal power. Surface EMG signals were measured in 10 lower limb muscles. A decomposition algorithm (nonnegative matrix factorization) was applied to a set of 40 consecutive pedaling cycles to differentiate muscle synergies. We selected the least number of synergies that provided 90% of the variance accounted for VAF. Using this criterion, three synergies were identified for all of the subjects, accounting for 93.5+/-2.0% of total VAF, with VAF for individual muscles ranging from 89.9+/-8.2% to 96.6+/-1.3%. Each of these synergies was quite similar across all subjects, with a high mean correlation coefficient for synergy activation coefficients (0.927+/-0.070, 0.930+/-0.052, and 0.877+/-0.110 for synergies 1-3, respectively) and muscle synergy vectors (0.873+/-0.120, 0.948+/-0.274, and 0.885+/-0.129 for synergies 1-3, respectively). Despite a large consistency across subjects in the weighting of several monoarticular muscles into muscle synergy vectors, we found larger interindividual variability for another monoarticular muscle (soleus) and for biarticular muscles (rectus femoris, gastrocnemius lateralis, biceps femoris, and semimembranosus). This study demonstrated that pedaling is accomplished by the combination of the similar three muscle synergies among trained cyclists. The interindividual variability of EMG patterns observed during pedaling does not represent differences in the locomotor strategy for pedaling. PMID- 20299612 TI - Reduction of total lung capacity in obese men: comparison of total intrathoracic and gas volumes. AB - Restriction of total lung capacity (TLC) is found in some obese subjects, but the mechanism is unclear. Two hypotheses are as follows: 1) increased abdominal volume prevents full descent of the diaphragm; and 2) increased intrathoracic fat reduces space for full lung expansion. We have measured total intrathoracic volume at full inflation using magnetic resonance imaging (MRI) in 14 asymptomatic obese men [mean age 52 yr, body mass index (BMI) 35-45 kg/m2] and 7 control men (mean age 50 yr, BMI 22-27 kg/m2). MRI volumes were compared with gas volumes at TLC. All measurements were made with subjects supine. Obese men had smaller functional residual capacity (FRC) and FRC-to-TLC ratio than control men. There was a 12% predicted difference in mean TLC between obese (84% predicted) and control men (96% predicted). In contrast, differences in total intrathoracic volume (MRI) at full inflation were only 4% predicted TLC (obese 116% predicted TLC, control 120% predicted TLC), because mediastinal volume was larger in obese than in control [heart and major vessels (obese 1.10 liter, control 0.87 liter, P=0.016) and intrathoracic fat (obese 0.68 liter, control 0.23 liter, P<0.0001)]. As a consequence of increased mediastinal volume, intrathoracic volume at FRC in obese men was considerably larger than indicated by the gas volume at FRC. The difference in gas volume at TLC between the six obese men with restriction, TLC<80% predicted (OR), and the eight obese men with TLC>80% predicted (ON) was 26% predicted TLC. Mediastinal volume was similar in OR (1.84 liter) and ON (1.73 liter), but total intrathoracic volume was 19% predicted TLC smaller in OR than in ON. We conclude that the major factor restricting TLC in some obese men was reduced thoracic expansion at full inflation. PMID- 20299613 TI - A phenomenological model that predicts forces generated when electrical stimulation is superimposed on submaximal volitional contractions. AB - Superimposition of electrical stimulation during voluntary contractions is used to produce functional movements in individuals with central nervous system impairment, to evaluate the ability to activate a muscle, to characterize the nature of fatigue, and to improve muscle strength during postsurgical rehabilitation. Currently, the manner in which voluntary contractions and electrically elicited forces summate is not well understood. The objective of the present study is to develop a model that predicts the forces obtained when electrical stimulation is superimposed on a volitional contraction. Quadriceps femoris muscles of 12 able-bodied subjects were tested. Our results showed that the total force produced when electrical stimulation was superimposed during a volitional contraction could be modeled by the equation T=V+S[(MaxForce V)/MaxForce]N, where T is the total force produced, V is the force in response to volitional contraction alone, S is the force response to the electrical stimulation alone, MaxForce is the maximum force-generating ability of the muscle, and N is a parameter that we posit depends on the differences in the motor unit recruitment order and firing rates between volitional and electrically elicited contractions. In addition, our results showed that the model predicted accurately (intraclass correlation coefficient>or=0.97) the total force in response to a wide range of stimulation intensities and frequencies superimposed on a wide range of volitional contraction levels. Thus the model will be helpful to clinicians and scientists to predict the amount of stimulation needed to produce the targeted force levels in individuals with partial paralysis. PMID- 20299614 TI - A common haplotype and the Pro582Ser polymorphism of the hypoxia-inducible factor 1alpha (HIF1A) gene in elite endurance athletes. AB - Hypoxia-inducible factor-1alpha (HIF1A) is a transcription factor regulating several genes in response to hypoxic stimuli. HIF1A target genes code for proteins involved in oxygen transport, glycolytic enzymes, and glucose transporters. We investigated whether single-nucleotide polymorphisms and haplotypes in the HIF1A gene are associated with endurance performance in the Genathlete cohort, which includes 316 Caucasian male elite endurance athletes (EEA) with a maximal oxygen uptake of 79.0+/-3.5 ml.kg(-1).min(-1) (mean+/-SD) and 304 Caucasian male sedentary controls with a maximal oxygen uptake of 40.1+/ 7.0 ml.kg(-1).min(-1). Six single-nucleotide polymorphisms (rs1951795, rs11158358, rs2301113, rs11549465, rs115494657, rs17099207) were genotyped with the TaqMan system. We found a nominal significant tendency for a difference between the two groups for HIF1A Pro582Ser (rs11549465) genotype distributions (Pchi2=0.017). Homozygotes of the Pro genotype were slightly more frequent in athletes than in controls (84 vs. 75%). Compared with Ser carriers, the odds ratio (OR) of being an EEA in Pro/Pro homozygotes was 1.77 [95% confidence interval (CI): 1.18-2.67, P=0.006] compared with the other genotypes. A common HIF1A haplotype (frequency: 15%), including the rs11549465 Pro allele and the minor A allele of rs17099207 in the 3' flanking region of the gene, showed a significant association with EEA status (OR: 2.37, 95% CI: 1.21-4.66, P=0.012), whereas the most prevalent haplotype (frequency: 59%) comprising the rs11549465 Pro allele and the major G allele of rs1709920 showed no association with EEA status (OR: 0.93, 95% CI: 0.58-1.50, P=0.769). We found preliminary evidence that the HIF1A Pro582Ser polymorphism and a common haplotype of the HIF1A gene may be associated with EEA status in Caucasian men. PMID- 20299615 TI - Short-term exercise training prevents micro- and macrovascular disease following coronary stenting. AB - The purpose of this study was to determine the effects of exercise on coronary blood flow and macrovascular atherosclerosis in response to stent deployment. Male Yucatan swine were placed on a control diet (C); on a high-fat/cholesterol diet (hypercholesterolemic; H); or on a high-fat/cholesterol diet and aerobically exercise trained (HX) starting after 36 wk on the diet. All pigs underwent coronary angiography and intravascular ultrasound (IVUS) guided placement of a bare metal stent in the circumflex coronary artery after 40 wk on diets and 3 wk later pigs underwent repeat angiography and IVUS and coronary blood flow (CBF) measurement. Average peak velocity (APV) was measured under basal conditions and in response to intracoronary application of the endothelium-independent vasodilator adenosine and the endothelium-dependent vasodilator bradykinin. There was a similar approximately 8-fold increase in total cholesterol in H and HX compared with control. Baseline CBF was increased above control and H in HX (P<0.05). At all doses adenosine-induced CBF was impaired in H, but preserved in HX. Similarly, bradykinin-induced CBF was impaired in H vs. control, yet was potentiated in HX. Microvessel density was decreased in H and preserved in HX vs. control. Native atheroma in HX was lower relative to H and control, while in stent stenosis in HX was not different from H. Hyperlipidemia-induced microvascular dysfunction after stent deployment may be a result of reduction in microvessel density. This is the first report that short-term exercise training near the time of stenting prevents stent-induced microvascular dysfunction and attenuates native atheroma independent of changes in plasma cholesterol in this porcine model. PMID- 20299616 TI - Missing links in pressure ulcer research--an interdisciplinary overview. AB - This paper surveys the literature on the etiology of sitting-acquired deep tissue pressure ulcers from three different viewpoints. The first viewpoint is identification of risk factors related to seated posture. The second viewpoint focuses on the external factors that can cause necrosis to human cells, such as ischemia and compression. The third viewpoint focuses on computational models of the human buttocks to calculate where stress concentrations occur. Each viewpoint contributes to the understanding of pressure ulcer etiology, but in combination they cover the multiple scales from cell to organism, and the combined insight can provide important information toward a full understanding of the phenomenon. It is concluded that the following three questions must be answered by future research. 1) Does compressive stress alone explain cell death, or is it necessary to consider the full three-dimensional strain tensor in the tissues? 2) How does the change in posture-induced load applied on the human buttocks change the stress distribution in the deep muscle tissue? 3) Is it possible to optimize the seated posture in a computational model to reduce the deeper tissue loads? PMID- 20299617 TI - Onset of obesity in carboxypeptidase E-deficient mice and effect on airway responsiveness and pulmonary responses to ozone. AB - When compared with lean, wild-type mice, obese Cpefat mice, 14 wk of age and older, manifest innate airway hyperresponsiveness (AHR) to intravenous methacholine and enhanced pulmonary inflammation following acute exposure to ozone (O3). The purpose of this study was to examine the onset of these augmented pulmonary responses during the onset of obesity. Thus airway responsiveness and O3-induced pulmonary inflammation and injury were examined in 7- and 10-wk-old Cpefat and age-matched, wild-type, C57BL/6 mice. Compared with age-matched controls, 7- and 10-wk-old Cpefat mice were approximately 25 and 61% heavier, respectively. Airway responsiveness to intravenous methacholine was assessed via forced oscillation in unexposed Cpefat and wild-type mice. The 10- but not 7-wk old Cpefat mice exhibited innate AHR. O3 exposure (2 ppm for 3 h) increased markers of pulmonary inflammation and injury in the bronchoalveolar lavage fluid of all mice. However, most markers were greater in Cpefat vs. wild-type mice, regardless of age. Serum levels of leptin, a satiety hormone and proinflammatory cytokine, were increased in Cpefat vs. wild-type mice of both age groups, but the serum levels of other systemic inflammatory markers were greater only in 10-wk old Cpefat vs. wild-type mice. These results demonstrate that a 25% increase in body weight is sufficient to augment pulmonary responses to O3, but innate AHR is not manifest until the mice become much heavier. These results suggest that the mechanistic bases for these responses are different and may develop according to the nature and degree of the chronic systemic inflammation that is present. PMID- 20299619 TI - Does your (genetic) alphabet soup spell "runner"? PMID- 20299620 TI - On the regulation of the blood supply to the brain: old age concepts and new age ideas. PMID- 20299618 TI - Increased intramuscular lipid synthesis and low saturation relate to insulin sensitivity in endurance-trained athletes. AB - Intramuscular triglyceride (IMTG) has received considerable attention as a potential mechanism promoting insulin resistance. Endurance-trained athletes have high amounts of IMTG but are insulin sensitive, suggesting IMTG content alone does not change insulin action. Recent data suggest increased muscle lipid synthesis protects against fat-induced insulin resistance. We hypothesized that rates of IMTG synthesis at rest would be increased in athletes compared with controls. Eleven sedentary men and 11 endurance-trained male cyclists participated in this study. An intravenous glucose tolerance test was performed to assess insulin action. After 3 days of dietary control and an overnight fast, [13C16]palmitate was infused at 0.0174 micromol.kg(-1).min(-1) for 4 h, followed by a muscle biopsy to measure isotope incorporation into IMTG and diacylglycerol. Compared with controls, athletes were twice as insulin sensitive (P=0.004) and had a significantly greater resting IMTG concentration (athletes: 20.4+/-1.6 microg IMTG/mg dry wt, controls: 14.5+/-1.8 microg IMTG/mg dry wt, P=0.04) and IMTG fractional synthesis rate (athletes: 1.56+/-0.37%/h, controls: 0.61+/ 0.15%/h, P=0.03). Stearoyl-CoA desaturase 1 mRNA expression (P=0.02) and protein content (P=0.03) were also significantly greater in athletes. Diacylglycerol, but not IMTG, saturation was significantly less in athletes compared with controls (P=0.002). These data indicate endurance-trained athletes have increased synthesis rates of skeletal muscle IMTG and decreased saturation of skeletal muscle diacylglycerol. Increased synthesis rates are not due to recovery from exercise and are likely adaptations to chronic endurance exercise training. PMID- 20299621 TI - Adiposity-independent sympathetic activity in black men. AB - Obesity is thought to lead to sympathetic overactivity as a compensatory adjustment to weight gain. However, most of the experimental support for the hypothesis has been derived from white cohorts. Our previous study in blacks indicated that sympathetic nerve activity (SNA) is closely correlated with body mass index only in women, whereas, in black men, SNA is elevated and dissociated from adiposity (Abate et al., Hypertension 38: 379-383, 2001). To further determine whether total and regional adiposity are determinants of SNA in blacks, we performed a prospective weight loss study in 12 normotensive obese black men and 9 obese black women. SNA, body mass index, and abdominal fat mass were measured before and 16 wk after hypocaloric diet. The major new findings are that, in obese black men, the dietary-induced weight loss of 11.3+/-0.8 kg resulted in reduction in plasma leptin, insulin, and visceral abdominal fat but had no effect on SNA (from baseline of 26+/-4 to 28+/-3 bursts/min, P=not significant). In contrast, in black women, weight loss of 8.0+/-0.9 kg caused similar reductions in plasma leptin, insulin, and visceral abdominal fat and led to a reduction in SNA by 40% (from baseline of 22+/-2 to 13+/-3 bursts/min, P<0.05). In conclusion, these new data from this prospective study provide strong support for a major adiposity-independent sympathetic activity in black men and adiposity-related sympathetic activity in black women. PMID- 20299622 TI - Myocellular basis for tapering in competitive distance runners. AB - The purpose of this study was to examine the effects of a 3-wk taper on the physiology of competitive distance runners. We studied seven collegiate distance runners (20+/-1 yr, 66+/-1 kg) before and after a 3-wk taper. The primary measures included 8-km cross-country race performance, gastrocnemius single muscle fiber size and function (peak force, shortening velocity, and power), baseline and exercise-induced gene expression 4 h after a standardized 8-km run, citrate synthase activity, and maximal and submaximal cardiovascular physiology (oxygen consumption, ventilation, heart rate, and respiratory exchange ratio). Race performance improved by 3% following taper (P<0.05). Myosin heavy chain (MHC) IIa fiber diameter (+7%, P<0.05), peak force (+11%, P=0.06), and absolute power (+9%, P<0.05) increased following taper. In addition to the MHC IIa adaptations, taper elicited a distinct postexercise gene response. Specifically, the induction of MuRF-1 was attenuated following taper, whereas MRF4, HSP 72, and MT-2A displayed an exaggerated response (P<0.05). No changes were observed in MHC I size or function, baseline gene expression, citrate synthase activity, or cardiovascular function. Our findings show that tapered training in competitive runners promoted MHC IIa fiber remodeling and an altered transcriptional response following the same exercise perturbation, with no adverse affects on aerobic fitness. Together, these results provide a myocellular basis for distance runners to taper in preparation for peak performance. PMID- 20299623 TI - A novel user-friendly score (HAS-BLED) to assess 1-year risk of major bleeding in patients with atrial fibrillation: the Euro Heart Survey. AB - OBJECTIVE: Despite extensive use of oral anticoagulation (OAC) in patients with atrial fibrillation (AF) and the increased bleeding risk associated with such OAC use, no handy quantification tool for assessing this risk exists. We aimed to develop a practical risk score to estimate the 1-year risk for major bleeding (intracranial, hospitalization, hemoglobin decrease > 2 g/L, and/or transfusion) in a cohort of real-world patients with AF. METHODS: Based on 3,978 patients in the Euro Heart Survey on AF with complete follow-up, all univariate bleeding risk factors in this cohort were used in a multivariate analysis along with historical bleeding risk factors. A new bleeding risk score termed HAS-BLED (Hypertension, Abnormal renal/liver function, Stroke, Bleeding history or predisposition, Labile international normalized ratio, Elderly (> 65 years), Drugs/alcohol concomitantly) was calculated, incorporating risk factors from the derivation cohort. RESULTS: Fifty-three (1.5%) major bleeds occurred during 1-year follow up. The annual bleeding rate increased with increasing risk factors. The predictive accuracy in the overall population using significant risk factors in the derivation cohort (C statistic 0.72) was consistent when applied in several subgroups. Application of the new bleeding risk score (HAS-BLED) gave similar C statistics except where patients were receiving antiplatelet agents alone or no antithrombotic therapy, with C statistics of 0.91 and 0.85, respectively. CONCLUSION: This simple, novel bleeding risk score (HAS-BLED) provides a practical tool to assess the individual bleeding risk of real-world patients with AF, potentially supporting clinical decision making regarding antithrombotic therapy in patients with AF. PMID- 20299624 TI - A CT scan score for the assessment of lung disease in children with common variable immunodeficiency disorders. AB - BACKGROUND: The prevalence and severity of structural lung disease in children with common variable immunodeficiency (CVID) disorders is not well known, and a dedicated CT scanning protocol and CT scan scoring system have not been described in this category. METHODS: This was a cohort study of 54 children (34 CVID, 20 CVID-like disorder) in a stable condition who underwent volumetric inspiratory and end-expiratory CT scans. Scans were scored for airway abnormalities, interstitial and parenchymal lung disease, and lymphadenopathy using a newly developed CT scan scoring system. Scores were normalized to a 0% to 100% scale. Observer agreement was assessed using an intraclass correlation coefficient (Ri). Prevalence and severity of CT scan abnormalities were calculated. RESULTS: Structural lung disease was common (85%-93%), but usually mild as reflected in the relatively low scores (bronchiectasis score 2.8% +/- 6.4%). Moderate-to severe bronchiectasis was found in three (5%) patients. Expiratory air trapping was the most common finding, found in 71% to 80%, but often in a mild form; application of a cut off level of > 10% reduced its prevalence to 33% to 38%. In 9% to 15% of all patients, air trapping was the only abnormality. Multiple lung nodules were seen in 24% to 25% and could disappear after corticosteroid treatment. Observer agreement was moderate (Ri 0.6-0.79) to good (Ri > 0.8) for all items and the composite scores, except airway wall thickening. CONCLUSION: In children with CVID disorders, mild structural lung disease is common. Expiratory CT scans show the most frequent abnormality, air trapping. The occurrence of (silent) lung disease progression and the clinical impact of CT scans require further investigations. PMID- 20299625 TI - Air pollution and prevalence of bronchitic symptoms among children in Taiwan. AB - BACKGROUND: There were limited studies concerning ambient air pollution exposure on development of bronchitic symptoms among children. These studies provided suggestive but inconclusive results. Therefore, the objective of this study is to assess the association between air pollutants and the prevalence of bronchitic symptoms in the Taiwan Children Health Study. METHODS: We conducted a nationwide cross-sectional study of 5,049 Taiwanese children in 2007. Routine air pollution monitoring data were used for sulfur dioxide (SO(2)), nitrogen dioxides (NO(2)), ozone (O(3)), carbon monoxide (CO), and particles with an aerodynamic diameter <= 2.5 MUm (PM(2.5)). The exposure parameters were calculated using the between community 3-year average concentration. The effect estimates were presented as odds ratios (ORs) per interquartile changes for SO(2), NO(2), O(3), CO, and PM(2.5). RESULTS: In the two-stage hierarchical model adjusting for confounding, the prevalence of bronchitic symptoms with asthma was positively associated with the between-community 3-year average concentrations of NO(2) (adjusted OR, 1.81 per 8.79 ppb; 95% CI, 1.14-2.86), and CO (OR, 1.31 per 105 ppb; 95% CI, 1.04 1.64). The prevalence of phlegm with no asthma was related to O(3) (OR, 1.32 per 8.77 ppb; 95% CI, 1.06-1.63). CONCLUSIONS: The results suggest that long-term exposure to outdoor air pollutants, such as NO(2), CO, and O(3), may increase the prevalence of bronchitic symptoms among children. PMID- 20299626 TI - Leukocyte telomere length and plasma catestatin and myeloid-related protein 8/14 concentrations in children with obstructive sleep apnea. AB - BACKGROUND: Obstructive sleep apnea (OSA) is common in children and leads to multiple end-organ morbidities induced by the cumulative burden of oxidative stress and inflammation. Leukocyte telomere length (LTL) reflects not only chronologic age but also the burden of disease. We hypothesized that LTL would be decreased in children with OSA. METHODS: Two hundred thirteen children (mean age, 7.7 +/- 1.4 years) were included after a sleep study and a morning blood sample. LTL was examined by quantitative polymerase chain reaction in a case-control setting involving 111 OSA cases and 102 controls. Myeloid-related protein (MRP) 8/14 and catestatin plasma levels also were assayed using enzyme-linked immunosorbent assay. RESULTS: Log LTL was significantly increased and OSA severity dependently increased in children (P = .012), was positively associated with apnea-hypopnea index (AHI) (r = 0.236; P < .01), and was inversely correlated with age (r = -0.145; P < .05). In a multivariate regression model, LTL was independently associated with AHI (beta = 0.28; P = .002) after adjusting for age, sex, BMI z score, and race. Children with OSA exhibited higher BP (P < .05), lower plasma catestatin (P = .009), and higher MRP 8/14 levels (P < .001) than controls. Of note, children with the lowest plasma catestatin levels (< 1.39 ng/mL) had 5.2-fold increased odds of moderate-to-severe OSA (95% CI, 1.19-23.4 ng/mL; P < .05) after adjusting for confounding variables. CONCLUSIONS: In pediatric OSA, LTL is longer rather than shorter. Children with OSA have reduced plasma catestatin levels and increased BP along with increased MRP 8/14 levels that exhibit AHI dependencies. Thus, catestatin and MRP 8/14 levels may serve as biomarkers for cardiovascular risk in the context of pediatric OSA. However, the implications of increased LTL in children with OSA remain to be defined. PMID- 20299627 TI - Laser tissue welding in lung and tracheobronchial repair: an animal model. AB - BACKGROUND: Violation of the integrity of the airway (pulmonary parenchymal air leak or tracheobronchial injury) remains a challenging problem in chest medicine and thoracic surgery. Tissue sealants such as fibrin glue have been suggested to improve outcomes but they are still associated with significant failure rates. Laser tissue welding (LTW) is an alternative method that produces wound repairs that are significantly stronger than those of fibrin glue and may be used to repair air leaks. METHODS: We used an Institutional Animal Care and Use Committees-approved New Zealand white rabbit model of lung parenchymal and tracheal injury. Lung wounds (n = 8 per condition) were created and either left open or repaired using fibrin glue or LTW. Tracheal wounds (n = 5 per condition) were created using incisions in the membranous and cartilaginous portions or by removing a tracheal ring, and were repaired using LTW. Within each tissue type, the burst strength of the wounds was measured using a digital manometer and were compared with one another using a two-tailed, paired Student t test. RESULTS: Among the lung injuries, the burst strength of the LTW repair (19.95 +/- 4.98 mm Hg) was significantly stronger than that of the fibrin glue repair or open wound (10.53 +/- 5.01 mm Hg, P = .001, and 7.61 +/- 2.64 mm Hg, P < .001, respectively). Among the tracheal injuries, the burst strength of the membranous incision (101.00 +/- 20.25 mm Hg) was significantly higher than that of the cartilaginous incision (75.08 +/- 10.50 mm Hg, P = .03) but not that of the cartilaginous defect (77.34 +/- 12.35 mm Hg). CONCLUSIONS: LTW is capable of sealing wounds in the tracheobronchial tree and can produce bonds that are twice as strong as fibrin glue in lung parenchyma. LTW may be a better alternative than fibrin glue in the repair of injuries to the airway. PMID- 20299628 TI - Treatment effects of low-dose theophylline combined with an inhaled corticosteroid in COPD. AB - BACKGROUND: Inhaled corticosteroids (ICS) have proved disappointing at reducing airway inflammation in COPD. However, previous studies indicate that low doses of theophylline enhance the activity of a key corticosteroid-associated corepressor protein, histone deacetylase (HDAC)2, which is reduced in COPD. This may account, at least in part, for the relative corticosteroid resistance. Thus, combination therapy with an ICS and low-dose theophylline may be of benefit in the treatment of COPD. METHODS: To test the hypothesis that ICS and theophylline have a greater therapeutic effect than theophylline alone, 30 patients with COPD were treated with placebo theophylline capsules and either inhaled fluticasone propionate (FP) (500 microg bid) or inhaled placebo for 4 weeks in a double-dummy, randomized, double-blind, parallel study. After a 2-week washout, patients were given active theophylline capsules (plasma level of 8.8-12.4 mg/L). RESULTS: In an across-arm comparison, combination treatment with FP and theophylline did not reduce total sputum neutrophils but significantly reduced total sputum eosinophils (P < .05). Additional across-arm comparisons suggest a further reduction in percentage sputum neutrophils and sputum chemokine (C-X-C motif) ligand 8/IL-8 (P < .05). Furthermore, within-arm observational data also demonstrated increases in forced midexpiratory flow rate and FEV(1)% predicted (P < .05) following combination treatment only. In an open-label study, low-dose theophylline when added to inhaled FP increased total HDAC activity in peripheral blood monocytes ninefold (P < .01) compared with FP alone from the same patients with COPD. CONCLUSIONS: Combination therapy with an inhaled corticosteroid and low-dose theophylline may attenuate airway inflammation in patients with COPD. TRIAL REGISTRATION: clinicaltrials.gov; Identifier NCT00241631. PMID- 20299629 TI - Swallowing dysfunction in nonneurologic critically ill patients who require percutaneous dilatational tracheostomy. AB - BACKGROUND: The aim of this study was to determine the incidence of swallowing dysfunction in nonneurologic critically ill patients who require percutaneous dilatational tracheostomy (PDT) for prolonged mechanical ventilation (MV) and to compare the duration of the cannulation period and length of stay in the critical care unit (CCU) in patients with and without swallowing dysfunction. METHODS: A total of 40 consecutive patients without neurologic disorders who require PDT for prolonged MV were included. Previous to the tracheostomy decannulation process, an otolaryngologist performed a fiberoptic endoscopic evaluation of swallowing (FEES). We used analysis of variance for the analysis; the results are presented as mean values +/- SD. RESULTS: Mean age was 62 +/- 15 years. Acute Physiology and Chronic Health Evaluation II and Sequential Organ Failure Assessment scores were 21 +/- 2 and 9 +/- 1, respectively. Time of MV previous to PDT was 20 +/- 11 days, total MV duration was 38 +/- 16 days, and CCU stay was 63 +/- 27 days. The incidence of swallowing dysfunction in this group of patients was 38% (15/40). No difference was found in the age or time period of MV previous to PDT between groups. The time period between FEES to tracheostomy decannulation process was 19 +/- 11 days in patients with swallowing dysfunction vs 2 +/- 4 days in those patients without dysfunction (P < .001). Patients who developed swallowing dysfunction stayed longer in the CCU (69 +/- 23 vs 47 +/- 19 days, P < .01). CONCLUSIONS: Nearly 40% of nonneurologic critically ill patients requiring PDT for prolonged MV presented swallowing dysfunction and experienced a significant delay in their tracheostomy decannulation process. PMID- 20299630 TI - CT scan features as predictors of patient outcome after bronchial intervention in endobronchial TB. AB - BACKGROUND: The purpose of this study was to identify the CT scan features that predict patient outcome after reexpansion procedures in patients with the fibrotic stage of endobronchial TB. METHODS: We retrospectively enrolled 30 patients (four men, 26 women) aged 32 +/- 11 years who had lobar or whole-lung atelectasis as sequela of endobronchial TB. Patients underwent helical CT scan examinations and subsequent reexpansion procedures for atelectasis, including balloon dilatation (n = 2), stent placement (n = 23), and surgical bronchoplasty (n = 5). Two thoracic radiologists evaluated the location and extent of airway narrowing, the extent of volume loss, parenchymal calcification, mucus plugging, and bronchiectasis within atelectasis on preprocedural CT scans. The success of reexpansion procedures was defined as the recovery of lung volume being > 80% of the estimated original volume as determined during follow-up imaging. Preprocedural CT scans and clinical features were compared for the results of the reexpansion procedures using the Wilcoxon two-sample test or Fisher exact test. RESULTS: Atelectasis was reexpanded in 30% (nine of 30) of patients after reexpansion procedures. The presence of parenchymal calcification and bronchiectasis within atelectasis showed a high tendency of failure in reexpansion procedures (P < .001). Mucus plugging, the extent of airway narrowing, volume loss on CT images, and endobronchial TB activity at the time of intervention did not affect the results (P > .05). Patients with successful results were significantly younger than those with unsatisfactory results. CONCLUSIONS: Parenchymal calcification and bronchiectasis within atelectasis are correlated with a high chance of failure in reexpansion procedures. Knowledge of CT scan features may help radiologists to predict the results of lung-conserving therapy to avoid unnecessary interventions. PMID- 20299631 TI - Chemokine (C-X-C motif) ligand 12/stromal cell-derived factor-1 is associated with leukocyte recruitment in asthma. AB - BACKGROUND: Asthma is characterized by allergic airway inflammatory response involving extensive leukocyte infiltration. The stromal cell-derived factor (SDF) 1 or chemokine (C-X-C motif) ligand 12 (CXCL12) attracts a number of cells, including resting T lymphocytes, monocytes, CD34(+) stem cells, basophils, and mature eosinophils. To date, however, the potential role of CXCL12/SDF-1 in relation to leukocyte recruitment in asthma has not been previously examined, to our knowledge. METHODS: Levels of CXCL12/SDF-1 in the BAL fluid (BALF) of 15 subjects with asthma and 13 healthy subjects were measured by enzyme-linked immunosorbent assay. Immunohistochemistry was performed to identify the cellular source of this chemokine. RESULTS: CXCL12/SDF-1 concentrations were significantly elevated in BALF from subjects with asthma compared with normal subjects (median 845 pg/mL, range, 296-1,700 pg/mL vs median 55 pg/mL, range 25-97 pg/mL; P < .001). Concentrations of CXCL12/SDF-1 correlated with macrophages (r = 0.728, P < .01), lymphocytes (r = 0.651, P < .01), and eosinophils (r = 0.765, P < .01). By immunohistochemistry, CXCL12/SDF-1 was localized to the airway epithelium and to a lesser extent to mononuclear cells. CONCLUSION: CXCL12/SDF-1 is released in high concentration in BALF of patients with asthma. The finding that concentrations of this chemokine correlated with leukocyte numbers in BALF suggests that this chemokine may contribute to the cell recruitment in asthma. PMID- 20299632 TI - Patient-controlled sedation: a novel approach to sedation management for mechanically ventilated patients. AB - BACKGROUND: Patient self-administration of medications for analgesia and procedural sedation is common. However, it is not known whether mechanically ventilated ICU patients can self-administer their own sedation to manage symptoms. METHODS: This descriptive pilot study examined the safety, adequacy, and satisfaction of patient-controlled sedation (PCS) with a convenience sample of critically ill, mechanically ventilated patients (N = 17) in the ICUs at University of Minnesota Medical Center, Fairview, Minneapolis, Minnesota. Dexmedetomidine was administered via a patient-demand infusion pump system for a maximum of 24 h. Pumps were programmed with basal infusion plus patient-triggered boluses; nurses adjusted the basal infusion based on a dosing algorithm. Data were collected on sedation adequacy, additional dosing of analgesics and sedatives, hemodynamic parameters, safety of PCS, patient satisfaction with PCS, and nurse satisfaction with PCS. RESULTS: Although a majority of the hemodynamic values were within the established safety parameters for the study, 25% of patients experienced mild adverse physiologic effects. Furthermore, despite patients' perception of sedation adequacy with PCS, 70% received supplemental opiates or benzodiazepine medications while participating in the study. Patients rated dexmedetomidine PCS favorably for self-management of anxiety, level of relaxation obtained, and comfort in self-administering sedation. Nurses also were generally satisfied with PCS as a method of sedation, dexmedetomidine as the sedative, and patient response to the sedation. CONCLUSIONS: PCS warrants further investigation as a means to promote comfort in mechanically ventilated critically ill patients. PMID- 20299633 TI - Patient-clinician communication: associations with important health outcomes among veterans with COPD. AB - BACKGROUND: High quality patient-clinician communication is widely advocated, but little is known about which health outcomes are associated with communication for patients with COPD. METHODS: Using a cross-sectional study of 342 veterans enrolled in a randomized controlled trial, we evaluated the association of communication, measured with the quality of communication (QOC) instrument, with subject-reported quality of clinician care, breathing problem confidence, and general self-rated health. We measured these associations using general estimating equations and adjusted odds ratios (OR) of patient-reported outcomes associated with one-point changes in QOC scores. RESULTS: Nearly one-half of the subjects reported receiving the best imaginable care (47%), whereas fewer reported being confident with their breathing problems all the time (29%) or in very good or excellent health (15%). General communication was associated with best-imagined quality of care (OR, 4.29; 95% CI, 2.84-6.48; P < .001) and confidence in dealing with breathing problems all the time (OR, 1.74; 95% CI, 1.34-2.25; P < .001) but not general self-rated health (OR, 1.19; 95% CI, 0.92 1.55; P = .19). Specific clinician behaviors with larger associations with higher quality care included listening, caring, and attentiveness. The associations between general communication and quality care increased over time (P for interaction .03). CONCLUSIONS: Communication between patients and clinicians is associated with quality of care and confidence in dealing with breathing problems, and this association may change over time. Attention to specific communication strategies may lead to improvements in the care of patients with COPD. PMID- 20299635 TI - Out of the shadows: Asian Americans, Native Hawaiians, and Pacific Islanders. PMID- 20299636 TI - Winston Wong, MD: leveling the field. PMID- 20299634 TI - Procalcitonin levels predict bacteremia in patients with community-acquired pneumonia: a prospective cohort trial. AB - BACKGROUND: Guidelines recommend blood culture sampling from hospitalized patients with suspected community-acquired pneumonia (CAP). However, the yield of true-positive results is low. We investigated the benefit of procalcitonin (PCT) on hospital admission to predict blood culture positivity in CAP. METHODS: This was a prospective cohort study with a derivation and validation set including 925 patients with CAP who underwent blood culture sampling on hospital admission. RESULTS: A total of 73 (7.9%) patients had true bacteremia (43 of 463 in the derivation cohort, 30 of 462 in the validation cohort). The area under the receiver operating characteristics curve of PCT in the derivation and validation cohorts was similar (derivation cohort, 0.83; 95% CI, 0.78-0.89; validation cohort, 0.79; 95% CI, 0.72-0.88). Overall, PCT was a significantly better predictor for blood culture positivity than WBC count, C-reactive protein, and other clinical parameters. In multivariate regression analysis, only antibiotic pretreatment (adjusted odds ratio, 0.25; P < .05) and PCT serum levels (adjusted odds ratio, 3.72; P < .001) were independent predictors. Overall, a PCT cutoff of 0.1 microg/L would enable reduction of the total number of blood cultures by 12.6% and still identify 99% of the positive blood cultures. Similarly, 0.25 microg/L and 0.5 microg/L cutoffs would enable reduction of blood cultures by 37% and 52%, respectively, and still identify 96% and 88%, respectively, of positive blood cultures. CONCLUSIONS: Initial PCT level accurately predicted blood culture positivity in patients with CAP. PCT measurement has the potential to reduce the number of drawn blood cultures in the emergency department and to implement a more targeted allocation of limited health-care resources. PMID- 20299637 TI - Advancing paternal and maternal age are both important for autism risk. PMID- 20299638 TI - Capacity-building assistance and structural challenges in HIV prevention services. PMID- 20299639 TI - George E. Bolling (1876-1945): founder of an early public health laboratory. PMID- 20299640 TI - Hidden in plain sight marketing prescription drugs to consumers in the twentieth century. AB - Although the public health impact of direct-to-consumer (DTC) pharmaceutical advertising remains a subject of great controversy, such promotion is typically understood as a recent phenomenon permitted only by changes in federal regulation of print and broadcast advertising over the past two decades. But today's omnipresent ads are only the most recent chapter in a longer history of DTC pharmaceutical promotion (including the ghostwriting of popular articles, organization of public-relations events, and implicit advertising of products to consumers) stretching back over the twentieth century. We use trade literature and archival materials to examine the continuity of efforts to promote prescription drugs to consumers and to better grapple with the public health significance of contemporary pharmaceutical marketing practices. PMID- 20299641 TI - Policy and system change and community coalitions: outcomes from allies against asthma. AB - OBJECTIVES: We assessed policy and system changes and health outcomes produced by the Allies Against Asthma program, a 5-year collaborative effort by 7 community coalitions to address childhood asthma. We also explored associations between community engagement and outcomes. METHODS: We interviewed a sample of 1477 parents of children with asthma in coalition target areas and comparison areas at baseline and 1 year to assess quality-of-life and symptom changes. An extensive tracking and documentation procedure and a survey of 284 participating individuals and organizations were used to ascertain policy and system changes and community engagement levels. RESULTS: A total of 89 policy and system changes were achieved, ranging from changes in interinstitutional and intrainstitutional practices to statewide legislation. Allies children experienced fewer daytime (P = .008) and nighttime (P = .004) asthma symptoms than comparison children. In addition, Allies parents felt less helpless, frightened, and angry (P = .01) about their child's asthma. Type of community engagement was associated with number of policy and system changes. CONCLUSIONS: Community coalitions can successfully achieve asthma policy and system changes and improve health outcomes. Increased core and ongoing community stakeholder participation rather than a higher overall number of participants was associated with more change. PMID- 20299642 TI - Preventing high blood pressure and promoting longevity. PMID- 20299643 TI - Neighborhoods and chronic disease onset in later life. AB - OBJECTIVES: To strengthen existing evidence on the role of neighborhoods in chronic disease onset in later life, we investigated associations between multiple neighborhood features and 2-year onset of 6 common conditions using a national sample of older adults. METHODS: Neighborhood features for adults aged 55 years or older in the 2002 Health and Retirement Study were measured by use of previously validated scales reflecting the built, social, and economic environment. Two-level random-intercept logistic models predicting the onset of heart problems, hypertension, stroke, diabetes, cancer, and arthritis by 2004 were estimated. RESULTS: In adjusted models, living in more economically disadvantaged areas predicted the onset of heart problems for women (odds ratio [OR] = 1.20; P < .05). Living in more highly segregated, higher-crime areas was associated with greater chances of developing cancer for men (OR = 1.31; P < .05) and women (OR = 1.25; P < .05). CONCLUSIONS: The neighborhood economic environment is associated with heart disease onset for women, and neighborhood level social stressors are associated with cancer onset for men and women. The social and biological mechanisms that underlie these associations require further investigation. PMID- 20299644 TI - Associations between racial discrimination, limited English proficiency, and health-related quality of life among 6 Asian ethnic groups in California. AB - OBJECTIVES: We examined the association of racial discrimination and limited English proficiency with health-related quality of life among Asian Americans in California. METHODS: We studied Chinese (n = 2576), Filipino (n = 1426), Japanese (n = 833), Korean (n = 1128), South Asian (n = 822), and Vietnamese (n = 938) respondents to the California Health Interview Survey in 2003 and 2005. We assessed health-related quality of life with the Centers for Disease Control and Prevention's measures of self-rated health, activity limitation days, and unhealthy days. RESULTS: Overall, Asians who reported racial discrimination or who had limited English proficiency were more likely to have poor quality of life, after adjustment for demographic characteristics. South Asian participants who reported discrimination had an estimated 14.4 more activity limitation days annually than South Asians who did not report discrimination. Results were similar among other groups. We observed similar but less consistent associations for limited English proficiency. CONCLUSIONS: Racial discrimination, and to a lesser extent limited English proficiency, appear to be key correlates of quality of life among Asian ethnic groups. PMID- 20299645 TI - Perinatal outcomes for Asian, Native Hawaiian, and other Pacific Islander mothers of single and multiple race/ethnicity: California and Hawaii, 2003-2005. AB - OBJECTIVES: We examined characteristics and birth outcomes of Asian/Pacific Islander (API) mothers to determine whether differences in outcomes existed between mothers of single race/ethnicity and multiple race/ethnicity. METHODS: We used data from California and Hawaii birth certificates from 2003 through 2005 to describe variation in birth outcomes for API subgroups by self-reported maternal race/ethnicity (single versus multiple race or API subgroup), and we also compared these outcomes to those of non-Hispanic White women. RESULTS: Low birthweight (LBW) and preterm birth (PTB) varied more among API subgroups than between mothers of single versus multiple race/ethnicity. After adjustment for sociodemographic and behavioral risk factors, API mothers of multiple race/ethnicity had outcomes similar to mothers of single race/ethnicity, with exceptions for multiple-race/ethnicity Chinese (higher PTB), Filipino (lower LBW and PTB), and Thai (higher LBW) subgroups. Compared with single-race non-Hispanic Whites, adverse outcomes were elevated for most API subgroups: only single race/ethnicity Korean mothers had lower rates of both LBW (3.4%) and PTB (5.6%); single-race/ethnicity Cambodian, Laotian, and Marshallese mothers had the highest rates of both LBW (8.8%, 9.2%, and 8.4%, respectively) and PTB (14.0%, 13.7%, and 18.8%, respectively). CONCLUSIONS: Strategies to improve birth outcomes for API mothers should consider variations in risk by API subgroup and multiple race/ethnicity. PMID- 20299646 TI - Decreases in smoking prevalence in Asian communities served by the Racial and Ethnic Approaches to Community Health (REACH) project. AB - OBJECTIVES: We examined trends in smoking prevalence from 2002 through 2006 in 4 Asian communities served by the Racial and Ethnic Approaches to Community Health (REACH) intervention. METHODS: Annual survey data from 2002 through 2006 were gathered in 4 REACH Asian communities. Trends in the age-standardized prevalence of current smoking for men in 2 Vietnamese communities, 1 Cambodian community, and 1 Asian American/Pacific Islander (API) community were examined and compared with nationwide US and state-specific data from the Behavioral Risk Factor Surveillance System. RESULTS: Prevalence of current smoking decreased dramatically among men in REACH communities. The reduction rate was significantly greater than that observed in the general US or API male population, and it was greater than reduction rates observed in the states in which REACH communities were located. There was little change in the quit ratio of men at the state and national levels, but there was a significant increase in quit ratios in the REACH communities, indicating increases in the proportions of smokers who had quit smoking. CONCLUSIONS: Smoking prevalence decreased in Asian communities served by the REACH project, and these decreases were larger than nationwide decreases in smoking prevalence observed for the same period. However, disparities in smoking prevalence remain a concern among Cambodian men and non-English-speaking Vietnamese men; these subgroups continue to smoke at a higher rate than do men nationwide. PMID- 20299647 TI - Comparison of disability rates among older adults in aggregated and separate Asian American/Pacific Islander subpopulations. AB - OBJECTIVES: We assessed the prevalence and adjusted odds of 4 types of disability among 7 groups of older Asian American/Pacific Islander (AAPI) subpopulations, both separately and aggregated, compared with non-Hispanic Whites. METHODS: Data were from the nationally representative 2006 American Community Survey, which included institutionalized and community-dwelling Hawaiian/Pacific Islander (n = 524), Vietnamese (n = 2357), Korean (n = 2082), Japanese (n = 3230), Filipino (n = 5109), Asian Indian (n = 2942), Chinese (n = 6034), and non-Hispanic White (n = 641 177) individuals aged 55 years and older. The weighted prevalence, population estimates, and odds ratios of 4 types of disability (functional limitations, limitations in activities of daily living, cognitive problems, and blindness or deafness) were reported for each group. RESULTS: Disability rates in older adults varied more among AAPI subpopulations than between non-Hispanic Whites and the aggregated Asian group. Asian older adults had, on average, better disability outcomes than did non-Hispanic Whites. CONCLUSIONS: This study provides the strongest evidence to date that exclusion of institutionalized older adults minimizes disparities in disabilities between Asians and Whites. The aggregation of Asians into one group obscures substantial subgroup variability and fails to identify the most vulnerable groups (e.g., Hawaiian/Pacific Islanders and Vietnamese). PMID- 20299648 TI - Disparities in breast cancer survival among Asian women by ethnicity and immigrant status: a population-based study. AB - OBJECTIVES: We investigated heterogeneity in ethnic composition and immigrant status among US Asians as an explanation for disparities in breast cancer survival. METHODS: We enhanced data from the California Cancer Registry and the Surveillance, Epidemiology, and End Results program through linkage and imputation to examine the effect of immigrant status, neighborhood socioeconomic status, and ethnic enclave on mortality among Chinese, Japanese, Filipino, Korean, South Asian, and Vietnamese women diagnosed with breast cancer from 1988 to 2005 and followed through 2007. RESULTS: US-born women had similar mortality rates in all Asian ethnic groups except the Vietnamese, who had lower mortality risk (hazard ratio [HR] = 0.3; 95% confidence interval [CI] = 0.1, 0.9). Except for Japanese women, all foreign-born women had higher mortality than did US-born Japanese, the reference group. HRs ranged from 1.4 (95% CI = 1.2, 1.7) among Koreans to 1.8 (95% CI = 1.5, 2.2) among South Asians and Vietnamese. Little of this variation was explained by differences in disease characteristics. CONCLUSIONS: Survival after breast cancer is poorer among foreign- than US-born Asians. Research on underlying factors is needed, along with increased awareness and targeted cancer control. PMID- 20299650 TI - Ke 'Ano Ola: Moloka'i's community-based healthy lifestyle modification program. AB - We evaluated a community-based 12-week healthy lifestyle program in Moloka'i, HI, called Ke 'Ano Ola, which was developed to decrease chronic disease risk through health education emphasizing weight loss, exercise, and risk factor reduction. Program leaders' strong commitment and positive role modeling, along with social and group support and community involvement, were key elements. A pre-post evaluation of weight, blood pressure, total cholesterol, and blood sugar showed significant improvements for weight (mean change [Delta] = -7.4 lbs; P < .001), systolic blood pressure (Delta = -3.8 mm Hg; P = .027), diastolic blood pressure (Delta = -4.6 mm Hg; P < .001), and total cholesterol (Delta = -9.7 mg/dL; P < .001). Attrition was low, with 89% of participants attending all 12 sessions. Our findings show that lifestyle improvements in a predominantly Native Hawaiian community are achievable in a support group setting. PMID- 20299649 TI - Discrimination and mental health-related service use in a national study of Asian Americans. AB - OBJECTIVES: We examined the association between perceived discrimination and use of mental health services among a national sample of Asian Americans. METHODS: Our data came from the National Latino and Asian American Study, the first national survey of Asian Americans. Our sample included 600 Chinese, 508 Filipinos, 520 Vietnamese, and 467 other Asians (n=2095). We used logistic regression to examine the association between discrimination and formal and informal service use and the interactive effect of discrimination and English language proficiency. RESULTS: Perceived discrimination was associated with more use of informal services, but not with less use of formal services. Additionally, higher levels of perceived discrimination combined with lower English proficiency were associated with more use of informal services. CONCLUSIONS: The effect of perceived discrimination and language proficiency on service use indicates a need for more bilingual services and more collaborations between formal service systems and community resources. PMID- 20299652 TI - Tuberculosis among persons born in the Philippines and living in the United States, 2000-2007. AB - OBJECTIVES: We examined demographic, clinical, and treatment outcome characteristics of Filipinos with tuberculosis (TB) in the United States. METHODS: We calculated TB case rates from US Census Bureau population estimates and National Tuberculosis Surveillance System data for US-born non-Hispanic Whites and for US residents born in the Philippines, India, China, Cambodia, Vietnam, Pakistan, and Korea--countries that are major contributors to the TB burden in the United States. We compared Filipinos with the other groups through univariate and multivariate analyses. RESULTS: Of 45,504 TB patients, 15.5% were Filipinos; 43.0% were other Asian/Pacific Islander groups; and 41.6% were Whites. Per 100 000 persons in 2007, the TB rate was 73.5 among Cambodians, 54.0 among Vietnamese, 52.1 among Filipinos, and 0.9 among Whites. Filipinos were more likely than other groups to be employed as health care workers and to have used private health care providers but less likely to be HIV positive and to be offered HIV testing. CONCLUSIONS: The relatively high TB rate among Filipinos indicates that TB control strategies should target this population. Providers should be encouraged to offer HIV testing to all TB patients. PMID- 20299651 TI - Perception of barriers to immunization among parents of Hmong origin in California. AB - OBJECTIVES: We explored factors associated with perception of barriers to immunization among parents of Hmong origin in California, whose children experience persistent immunization inequities even with health insurance. METHODS: A partnership of academic researchers and members of the Hmong community conducted a community-based participatory research project. We collected data in naturalistic settings with a standardized instrument. We analyzed responses from 417 parents and caregivers and created a structural equation model to determine factors that contributed to perceived barriers. RESULTS: Of 3 potential contributing factors to perceived barriers-nativity, socioeconomic position, and use of traditional Hmong health care (i.e., consulting shamans and herbalists) the latter 2 significantly predicted higher perceived barriers to immunization. Nativity, indicated by years in the United States, age of arrival in the United States, and English language fluency, did not predict perceived barriers. CONCLUSIONS: Interventions aimed at reducing immunization inequities should consider distinct sociocultural factors that affect immunization rates among different refugee and immigrant groups. PMID- 20299653 TI - Analyzing national health reform strategies with a dynamic simulation model. AB - Proposals to improve the US health system are commonly supported by models that have only a few variables and overlook certain processes that may delay, dilute, or defeat intervention effects. We use an evidence-based dynamic simulation model with a broad national scope to analyze 5 policy proposals. Our results suggest that expanding insurance coverage and improving health care quality would likely improve health status but would also raise costs and worsen health inequity, whereas a strategy that also strengthens primary care capacity and emphasizes health protection would improve health status, reduce inequities, and lower costs. A software interface allows diverse stakeholders to interact with the model through a policy simulation game called HealthBound. PMID- 20299654 TI - The forgotten treasure: bilingualism and Asian children's emotional and behavioral health. AB - OBJECTIVES: We investigated the relation between the language status of children and their behavioral and emotional well-being during their early school years. METHODS: Behavioral and emotional well-being were drawn from teacher-reported data and included externalizing and internalizing behaviors. Three-level growth curve analyses were conducted on a subsample (n = 12 586) of children from the Early Childhood Longitudinal Study, kindergarten cohort, who originated from Asian countries. US-born, non-Hispanic White children served as the comparison group. RESULTS: All children started with a similar level of internalizing and externalizing behaviors at kindergarten entry. The growth rate of problem behaviors was slowest in fluent bilingual and non-English-dominant bilingual children compared with White English-monolingual children. By contrast, problem behaviors increased at a significantly faster rate in non-English-monolingual children, who had the highest level of problem behaviors among all children by fifth grade. CONCLUSIONS: By fifth grade, fluent bilingual and non-English dominant bilingual children had the lowest levels of internalizing and externalizing behaviors, whereas non-English-monolingual children had the highest levels of both behavior problems. Our data suggest emotional and behavioral benefits of being bilingual. PMID- 20299656 TI - Health status and health services access and utilization among Chinese, Filipino, Japanese, Korean, South Asian, and Vietnamese children in California. AB - OBJECTIVES: We examined health status and health services access and utilization of Chinese, Filipino, Japanese, Korean, South Asian, Vietnamese, and non-Hispanic White children in California. METHODS: We analyzed aggregated data from the 2003 and 2005 California Health Interview Survey (648 Chinese, 523 Filipino, 235 Japanese, 308 Korean, 314 South Asian, 264 Vietnamese, and 8468 non-Hispanic White children aged younger than 12 years), examining the relationship between Asian ethnicities and outcomes. RESULTS: Compared with non-Hispanic White children, Korean children were 4 times more likely to lack health insurance; Filipino children were twice as likely to not have had recent contact with a doctor; Chinese, Korean, and Vietnamese children were less likely to have visited an emergency room in the past year; and Chinese, Korean, and Vietnamese children were more likely to be in fair or poor health. Age, gender, poverty, citizenship nativity status, health insurance, and parental marital and child health statuses were related to most outcomes. CONCLUSIONS: Asian ethnicities have heterogeneous health care access and utilization patterns, suggesting the need for targeted outreach to different Asian ethnic groups. PMID- 20299655 TI - Effects of socioeconomic status on colon cancer treatment accessibility and survival in Toronto, Ontario, and San Francisco, California, 1996-2006. AB - OBJECTIVES: We examined the differential effects of socioeconomic status on colon cancer care and survival in Toronto, Ontario, Canada, and San Francisco, California. METHODS: We analyzed registry data for colon cancer patients from Ontario (n = 930) and California (n = 1014), diagnosed between 1996 and 2000 and followed until 2006, on stage, surgery, adjuvant chemotherapy, and survival. We obtained socioeconomic data for individuals' residences from population censuses. RESULTS: Income was directly associated with lymph node evaluation, chemotherapy, and survival in San Francisco but not in Toronto. High-income persons had better survival rates in San Francisco than in Toronto. After adjustment for stage, survival was better for low-income residents of Toronto than for those of San Francisco. Middle- to low-income patients were more likely to receive indicated chemotherapy in Toronto than in San Francisco. CONCLUSIONS: Socioeconomic factors appear to mediate colon cancer care in urban areas of the United States but not in Canada. Improvements are needed in screening, diagnostic investigations, and treatment access among low-income Americans. PMID- 20299658 TI - Use of a smokers' quitline by Asian language speakers: results from 15 years of operation in California. AB - OBJECTIVES: We examined state quitline utilization by smokers who called Chinese , Vietnamese-, or Korean-language lines, and compared their usage rates to those of Asians and Whites calling the English-language line. METHODS: Using data from 15 years (1993-2008) of operation of the California quitline (which included data on 22 061 callers to Chinese, Korean, and Vietnamese lines) and from multiple California Health Interview Surveys, we computed the call rates for Whites, English-speaking Asians, and the 3 Asian-language groups. We also examined callers' demographics and where they heard about the quitline. RESULTS: Asian smokers who spoke English were significantly less likely than English-speaking White smokers to call the quitline (odds ratios range from 0.36 to 0.62). Smokers speaking 1 of the 3 Asian languages were no less likely than White smokers to call (odds ratios range from 0.82 to 3.25). More than 80% of those calling the Asian-language lines reported hearing about the quitline through mass media. CONCLUSIONS: Contrary to general expectation, smokers speaking Asian languages were just as likely to call the quitline as English-speaking White smokers. State quitlines should consider adding Asian-language lines to help address disparities in access to cessation services. PMID- 20299657 TI - Chlorpyrifos exposure and urban residential environment characteristics as determinants of early childhood neurodevelopment. AB - OBJECTIVES: We evaluated whether neighborhood characteristics correlated with early neurodevelopment and whether these characteristics confounded the previously reported association between exposure to chlorpyrifos (an organophosphate insecticide) and neurodevelopment. METHODS: We obtained prenatal addresses, chlorpyrifos exposure data, and 36-month Psychomotor Development Index (PDI) and Mental Development Index (MDI) scores for a birth cohort in New York City (born 1998-2002). We used data from the 2000 US Census to estimate measures of physical infrastructure, socioeconomic status, crowding, demographic composition, and linguistic isolation for 1-kilometer network areas around each child's prenatal address. Generalized estimating equations were adjusted for demographics, maternal education and IQ, prenatal exposure to tobacco smoke, caretaking environment quality, and building dilapidation. RESULTS: Of 266 children included as participants, 47% were male, 59% were Dominican, and 41% were African American. For each standard deviation higher in neighborhood percent poverty, the PDI score was 2.6 points lower (95% confidence interval [CI] = -3.7, -1.5), and the MDI score was 1.7 points lower (95% CI = -2.6, -0.8). Neighborhood level confounding of the chlorpyrifos-neurodevelopment association was not apparent. CONCLUSIONS: Neighborhood context and chlorpyrifos exposure were independently associated with neurodevelopment, thus providing distinct opportunities for health promotion. PMID- 20299660 TI - Morbidity risk at birth for Asian Indian small for gestational age infants. AB - Whether the traditional definition of small for gestational age (SGA) is an appropriate marker of risk for populations that have relatively lower birthweight is unclear. We determined proportions of White and Asian Indian SGA infants and those admitted to the special care nursery. Compared with White infants, Asian Indian infants were more likely to be SGA (14.5% versus 2.7%) and more likely to be admitted to the special care nursery (20.7% versus 3.7%), suggesting that traditional definitions of SGA may be applicable as a marker of risk. PMID- 20299659 TI - Effectiveness of a controlled trial to promote colorectal cancer screening in Vietnamese Americans. AB - OBJECTIVES: We conducted a controlled trial of a public education and provider intervention to increase colorectal cancer (CRC) screening rates among Vietnamese Americans, who typically have lower rates than non-Hispanic Whites. METHODS: The public education intervention included a Vietnamese-language CRC screening media campaign, distribution of health educational material, and a hotline. The provider intervention consisted of continuing medical education seminars, newsletters, and DVDs. Vietnamese in Alameda and Santa Clara Counties, California, received the intervention from 2004 to 2006; Vietnamese in Harris County, Texas, were controls and received no intervention. A quasi-experimental study design with pre- and postintervention surveys of the same 533 participants was used to evaluate the combined intervention. RESULTS: The postintervention-to preintervention odds ratio for having ever had a sigmoidoscopy or colonoscopy was 1.4 times greater in the intervention community than in the control community. Knowledge and attitudes mediated the effect of the intervention on CRC screening behavior. Media exposure mediated the effect of the intervention on knowledge. CONCLUSIONS: Improving CRC knowledge through the media contributed to the effectiveness of the intervention. PMID- 20299661 TI - Understanding the rapid increase in life expectancy in South Korea. AB - OBJECTIVES: We assessed life expectancy increases in the past several decades in South Korea by age and specific causes of death. METHODS: We applied Arriaga's decomposition method to life table data (1970-2005) and mortality statistics (1983-2005) to estimate age- and cause-specific contributions to changes in life expectancy. RESULTS: Reductions in infant mortality made the largest age-group contribution to the life expectancy increase. Reductions in cardiovascular diseases (particularly stroke and hypertensive diseases) contributed most to longer life expectancy between 1983 and 2005 (30% in males and 28% in females). Lower rates of stomach cancer, liver disease, tuberculosis, and external-cause mortality accounted for 30% of the male and 20% of the female increase in longevity. However, higher mortality from ischemic heart disease, lung and bronchial cancer, colorectal cancer, breast cancer, diabetes, and suicide offset gains by 10% in both genders. CONCLUSIONS: Rapid increases in life expectancy in South Korea were mostly achieved by reductions in infant mortality and in diseases related to infections and blood pressure. PMID- 20299662 TI - Short communication: genetic ablation of L-type Ca2+ channels abolishes depolarization-induced Ca2+ release in arterial smooth muscle. AB - RATIONALE: In arterial myocytes, membrane depolarization-induced Ca(2+) release (DICR) from the sarcoplasmic reticulum (SR) occurs through a metabotropic pathway that leads to inositol trisphosphate synthesis independently of extracellular Ca(2+) influx. Despite the fundamental functional relevance of DICR, its molecular bases are not well known. OBJECTIVE: Biophysical and pharmacological data have suggested that L-type Ca(2+) channels could be the sensors coupling membrane depolarization to SR Ca(2+) release. This hypothesis was tested using smooth muscle-selective conditional Ca(v)1.2 knockout mice. METHODS AND RESULTS: In aortic myocytes, the decrease of Ca(2+) channel density was paralleled by the disappearance of SR Ca(2+) release induced by either depolarization or Ca(2+) channel agonists. Ca(v)1.2 channel deficiency resulted in almost abolition of arterial ring contraction evoked by DICR. Ca(2+) channel-null cells showed unaltered caffeine-induced Ca(2+) release and contraction. CONCLUSION: These data suggest that Ca(v)1.2 channels are indeed voltage sensors coupled to the metabolic cascade, leading to SR Ca(2+) release. These findings support a novel, ion-independent, functional role of L-type Ca(2+) channels linked to intracellular signaling pathways in vascular myocytes. PMID- 20299664 TI - Multiplex coherent anti-stokes Raman spectroscopy images intact atheromatous lesions and concomitantly identifies distinct chemical profiles of atherosclerotic lipids. AB - RATIONALE: Lipids are a key component of atherogenesis. However, their physiological role on the progression of atherosclerosis including plaque vulnerability has not been clearly understood, because of the lack of appropriate tools for chemical assessment. OBJECTIVE: We aimed to develop a label-free chemical imaging platform based on multiplex coherent anti-Stokes Raman scattering (CARS) for the correlative study of the morphology and chemical profile of atherosclerotic lipids. METHODS AND RESULTS: Whole aortas from atherosclerotic apolipoprotein E knock-out mice were en face examined by multiplex CARS imaging and 4 distinctive morphologies of the lipids (intra/extracellular lipid droplets and needle-/plate-shaped lipid crystals) were classified. The chemical profiles of atherosclerotic lipids depending on morphologies were firstly identified from intact atheromatous tissue by multiplex CARS. We demonstrated that needle-/plate-shaped lipid crystals in advanced plaques had undergone a phase shift to the solid state with increased protein contents, implying that lipid modification had occurred beforehand. The validity of lipid-selective multiplex CARS imaging was supported by comparative results from oil red O staining and whole-mount immunohistochemistry. By spatial CARS analysis of atherosclerosis progression, we found greater accumulation of lipid crystals in both the lesser curvature of the aortic arch and the innominate artery. Furthermore, multiplex CARS measurement successfully demonstrated the effect of a drug, statin, on atherosclerotic lipids by showing the change of their chemical profiles. CONCLUSIONS: Multiplex CARS imaging directly provides intact morphologies of atherosclerotic lipids with correlative chemical information, thereby suggesting its potential applications in the investigation of lipid-associated disorders and the preclinical drug screening. PMID- 20299663 TI - Specific regulation of noncanonical p38alpha activation by Hsp90-Cdc37 chaperone complex in cardiomyocyte. AB - RATIONALE: p38 is an important stress activated protein kinase involved in gene regulation, proliferation, differentiation, and cell death regulation in heart. p38 kinase activity can be induced through canonical pathway via upstream kinases or by noncanonical autophosphorylation. The intracellular p38 kinase activity is tightly regulated and maintained at low level under basal condition. The underlying regulatory mechanism for canonical p38 kinase activation is well studied, but the regulation of noncanonical p38 autophosphorylation remains poorly understood. OBJECTIVE: We investigated the molecular basis for the regulation of noncanonical p38 autophosphorylation and its potential functional impact in cardiomyocytes. METHODS AND RESULTS: Using both proteomic and biochemical tools, we established that heat shock protein (Hsp)90-Cdc37 chaperones are part of the p38alpha signaling complex in mammalian cells both in vitro and in vivo. The Hsp90-Cdc37 chaperone complex interacts with p38 via direct binding between p38 and Cdc37. Cdc37 expression is both sufficient and necessary to suppress noncanonical p38 activation via autophosphorylation at either basal state or under TAB1 (TAK1 binding protein-1) induction. In contrast, Cdc37 expression has no impact on p38 activation by canonical upstream kinase MKK3 or oxidative stress. Furthermore, Hsp90 inhibition results in p38 activation via autophosphorylation, and p38 activity contribute to apoptotic cell death induced by Hsp90 inhibition. CONCLUSION: Our study has revealed a so far uncharacterized function of Hsp90-Cdc37 as an endogenous regulator of noncanonical p38 activity. PMID- 20299665 TI - Potential and failure of the ABCD2 score in stroke risk prediction after transient ischemic attack. PMID- 20299666 TI - Excess body weight and incidence of stroke: meta-analysis of prospective studies with 2 million participants. AB - BACKGROUND AND PURPOSE: A systematic review of the prospective studies addressing the relationship of overweight and obesity to major stroke subtypes is lacking. We evaluated the occurrence of a graded association between overweight, obesity, and incidence of ischemic and hemorrhagic stroke by a meta-analysis of cohort studies. METHODS: A search of online databases and relevant reviews was performed. Inclusion criteria were original article in English, prospective study design, follow-up > or = 4 years, indication of number of subjects exposed, and number of events across body mass index categories. Crude unadjusted relative risk (RR) and 95% CI were calculated for each study for overweight or obese compared with normal-weight categories. Log-transformed values and SE were used to calculate the pooled RR with random effects models; publication bias was checked. Additional analyses were performed using the multivariate estimates of risk reported in the individual studies. RESULTS: Twenty-five studies were included, with 2 274 961 participants and 30 757 events. RR for ischemic stroke was 1.22 (95% CI, 1.05-1.41) for overweight and 1.64 (95% CI, 1.36-1.99) for obesity, whereas RR for hemorrhagic stroke was 1.01 (95% CI, 0.88-1.17) and 1.24 (95% CI, 0.99-1.54), respectively. Subgroup and meta-regression analyses ruled out gender, population average age, body mass index and blood pressure, year of recruitment, year of study publication, and length of follow-up as significant sources of heterogeneity. The additional analyses relying on the published multivariate estimates of risk provided qualitatively similar results. CONCLUSIONS: Overweight and obesity are associated with progressively increasing risk of ischemic stroke, at least in part, independently from age, lifestyle, and other cardiovascular risk factors. PMID- 20299667 TI - Population-based study of ABCD2 score, carotid stenosis, and atrial fibrillation for early stroke prediction after transient ischemic attack: the North Dublin TIA study. AB - BACKGROUND AND PURPOSE: Transient ischemic attack (TIA) etiologic data and the ABCD(2) score may improve early stroke risk prediction, but studies are required in population-based cohorts. We investigated the external validity of the ABCD(2) score, carotid stenosis, and atrial fibrillation for prediction of early recurrent stroke after TIA. METHODS: Patients with TIA in the North Dublin city population (N=294 529) were ascertained by using overlapping hospital and community sources. The relations between individual ABCD(2) items, carotid stenosis, atrial fibrillation, and early stroke were examined. RESULTS: In confirmed TIA cases (n=443), carotid stenosis predicted 90-day stroke (hazard ratio=2.56; 95% CI, 1.27 to 5.15, P=0.003). Stroke risk rose with increasing grade of carotid stenosis, ranging from 5.4% (95% CI, 3.3% to 8.7%) with <50% stenosis to 17.2% (95% CI, 9.7% to 29.7%) with severe stenosis/occlusion (hazard ratio=3.3; 95% CI, 1.5 to 7.4, P=0.002). In confirmed TIA cases (n=443), the ABCD(2) score performed no better than chance for prediction of 90-day stroke (c statistic=0.55; 95% CI, 0.45 to 0.64), largely related to the 24.2% (8/33) of patients who experienced a recurrence and had low ABCD(2) scores (0-3). However, in nonspecialist-suspected TIA cases (n=700), the predictive utility improved for stroke at 28 (c-statistic=0.61; 95% CI, 0.50 to 0.72) and 90 (c-statistic=0.61; 95% CI, 0.52 to 0.71) days. CONCLUSIONS: In a population-based TIA cohort, significant predictive information was provided by carotid stenosis. The ABCD(2) score had predictive utility in patients with TIA suspected by nonspecialists. Low scores occurred in several patients with stroke recurrences, suggesting that caution is needed before using the score in isolation. PMID- 20299669 TI - Comparing pumps. PMID- 20299668 TI - ABCD2 score predicts severity rather than risk of early recurrent events after transient ischemic attack. AB - BACKGROUND AND PURPOSE: The ABCD(2) score predicts the early risk of stroke after transient ischemic attack (TIA). However, data on the severity of recurrent events would also be useful. Do patients with high scores also have more severe early recurrent strokes, perhaps further justifying hospital admission? Do patients with low scores have a low early risk of recurrent TIA as well as recurrent stroke? METHODS: We completed a prospective, population-based study in Oxfordshire, England, of 500 consecutive patients presenting with TIA from April 1, 2002, by using multiple methods of case ascertainment (Oxford Vascular Study). Recurrent TIA, minor stroke, and major stroke (National Institutes of Health Stroke Scale score >3 at the time of first assessment) were identified by face-to face follow-up. Predictive value was expressed as the area under the receiver operating characteristic curve. RESULTS: Of 500 patients with TIA, 55 had a recurrent TIA (11.0%; 95% CI, 8.3% to 13.7%) and 50 had a recurrent stroke (10.0%; 95% CI, 7.5% to 12.0%) within 7 days. The ABCD(2) score was highly predictive of major recurrent stroke (area under the receiver operating characteristic curve=0.80; 95% CI, 0.72 to 0.87, P<0.0001), weakly predictive of minor stroke (area under the receiver operating characteristic curve=0.57; 95% CI, 0.43 to 0.71, P=0.26), and inversely related to risk of recurrent TIA (area under the receiver operating characteristic curve=0.37; 95% CI, 0.29 to 0.44, P=0.001) (overall heterogeneity, P<0.0001). The score predicted stroke-related disability, length of stay for recurrent stroke, and hence, overall acute hospital care costs. CONCLUSIONS: The ABCD(2) score predicts severity of recurrent events after TIA, high scores being associated with major recurrent stroke and low scores with high rates of recurrent TIA. These findings have implications for cost-benefit analyses of policies on hospital admission for patients with high scores and for the advice given to patients with low scores. PMID- 20299670 TI - Robert Lefkowitz: godfather of G protein-coupled receptors. PMID- 20299671 TI - M cells in the human heart. PMID- 20299672 TI - Epicardial-myocardial signaling directing coronary vasculogenesis. AB - The establishment of the coronary circulation is critical for the development of the embryonic heart. Over the last several years, there has been tremendous progress in elucidating the pathways that control coronary development. Interestingly, many of the pathways that regulate the development of the coronary vasculature are distinct from those governing vasculogenesis in the rest of the embryo. It is becoming increasingly clear that coronary development depends on a complex communication between the epicardium, the subepicardial mesenchyme, and the myocardium mediated in part by secreted growth factors. This communication coordinates the growth of the myocardium with the formation of the coronary vasculature. This review summarizes our present understanding of the role of these growth factors in the regulation of coronary development. Continued progress in this field holds the potential to lead to novel therapeutics for the treatment of patients with coronary artery disease. PMID- 20299673 TI - Circadian clocks and vascular function. AB - The circadian clock regulates many aspects of physiology, including cardiovascular function. Internal oscillators exist in endothelial, smooth muscle cells, and fibroblasts of the vasculature. Vascular tone and thrombus formation, 2 key elements of vascular function with regard to adverse cardiovascular events, exhibit diurnal rhythmicity. In this review, we describe changes in vascular function that result from genetic disruption of discrete elements of the circadian clock. PMID- 20299674 TI - The RAGE axis: a fundamental mechanism signaling danger to the vulnerable vasculature. AB - The immunoglobulin superfamily molecule RAGE (receptor for advanced glycation end product) transduces the effects of multiple ligands, including AGEs (advanced glycation end products), advanced oxidation protein products, S100/calgranulins, high-mobility group box-1, amyloid-beta peptide, and beta-sheet fibrils. In diabetes, hyperglycemia likely stimulates the initial burst of production of ligands that interact with RAGE and activate signaling mechanisms. Consequently, increased generation of proinflammatory and prothrombotic molecules and reactive oxygen species trigger further cycles of oxidative stress via RAGE, thus setting the stage for augmented damage to diabetic tissues in the face of further insults. Many of the ligand families of RAGE have been identified in atherosclerotic plaques and in the infarcted heart. Together with increased expression of RAGE in diabetic settings, we propose that release and accumulation of RAGE ligands contribute to exaggerated cellular damage. Stopping the vicious cycle of AGE-RAGE and RAGE axis signaling in the vulnerable heart and great vessels may be essential in controlling and preventing the consequences of diabetes. PMID- 20299676 TI - Galactosemia diagnosis gets an upgrade. PMID- 20299677 TI - Reproducibility in serial C-reactive protein and interleukin-6 measurements in post-myocardial infarction patients: results from the AIRGENE study. AB - BACKGROUND: Among the numerous emerging biomarkers, high-sensitivity C-reactive protein (hsCRP) and interleukin-6 (IL-6) have received widespread interest, and a large database has been accumulated on their potential role as predictors of cardiovascular risk. The concentrations of inflammatory biomarkers, however, are influenced, among other things, by physiological variation, which is the natural within-individual variation occurring over time. Implementation of hsCRP and IL-6 measurement into clinical practice requires data on the reliability of such measurements. METHODS: We serially measured hsCRP and IL-6 concentrations in up to 6 blood samples taken at monthly intervals from 200 post-myocardial infarction patients who participated in the AIRGENE study. RESULTS: The mean (SD) of the ln transformed plasma concentrations (in milligrams per liter for hsCRP and nanograms per liter for IL-6) for all participants over all samples was 0.16 (1.04) for hsCRP and 0.76 (0.57) for IL-6, with no significant differences between men and women. The within-individual and analytical variance component for the ln-transformed hsCRP data was 0.37, and the between-individual variance component was 0.73. For the ln-transformed IL-6 data, these values were 0.11 and 0.22, respectively. A substantial part of the total variation in plasma hsCRP and IL-6 concentrations was explained by the between-individual variation (as a percentage of the total variance, 66.1% for the ln-transformed hsCRP data and 66.2% for the ln-transformed IL-6 data). For both markers, 2 measurements were needed to reach a sufficient reliability. CONCLUSIONS: Our results demonstrate considerable stability and good reproducibility for serial hsCRP and IL-6 measurements. Thus, there should be no major concern about misclassification in clinical practice if at least 2 subsequent measurements are taken. PMID- 20299675 TI - The promise of cell-based therapies for diabetic complications: challenges and solutions. AB - The discovery of endothelial progenitor cells (EPCs) in human peripheral blood advanced the field of cell-based therapeutics for many pathological conditions. Despite the lack of agreement about the existence and characteristics of EPCs, autologous EPC populations represent a novel treatment option for complications requiring therapeutic revascularization and vascular repair. Patients with diabetic complications represent a population of patients that may benefit from cellular therapy yet their broadly dysfunctional cells may limit the feasibility of this approach. Diabetic EPCs have decreased migratory prowess and reduced proliferative capacity and an altered cytokine/growth factor secretory profile that can accelerate deleterious repair mechanisms rather than support proper vascular repair. Furthermore, the diabetic environment poses additional challenges for the autologous transplantation of cells. The present review is focused on correcting diabetic EPC dysfunction and the challenges involved in the application of cell-based therapies for treatment of diabetic vascular complications. In addition, ex vivo and in vivo functional manipulation(s) of EPCs to overcome these hurdles are discussed. PMID- 20299678 TI - Enrichment and detection of rare alleles by means of snapback primers and rapid cycle PCR. AB - BACKGROUND: Selective amplification of minority alleles is often necessary to detect cancer mutations in clinical samples. METHODS: Minor-allele enrichment and detection were performed with snapback primers in the presence of a saturating DNA dye within a closed tube. A 5' tail of nucleotides on 1 PCR primer hybridizes to the variable locus of its extension product to produce a hairpin that selectively enriches mismatched alleles. Genotyping performed after rapid-cycle PCR by melting of the secondary structure identifies different variants by the hairpin melting temperature (T(m)). Needle aspirates of thyroid tissue (n = 47) and paraffin-embedded biopsy samples (n = 44) were analyzed for BRAF (v-raf murine sarcoma viral oncogene homolog B1) variant p.V600E, and the results were compared with those for dual hybridization probe analysis. Needle aspirates of lung tumors (n = 8) were analyzed for EGFR [epidermal growth factor receptor (erythroblastic leukemia viral (v-erb-b) oncogene homolog, avian)] exon 19 in frame deletions. RESULTS: Use of 18-s cycles and momentary extension times of "0 s" with rapid-cycle PCR increased the selective amplification of mismatched alleles. A low Mg(2+) concentration and a higher hairpin T(m) relative to the extension temperature also improved the detection limit of mismatched alleles. The detection limit was 0.1% for BRAF p.V600E and 0.02% for EGFR exon 19 in-frame deletions. Snapback and dual hybridization probe methods for allele quantification of the thyroid samples correlated well (R(2) = 0.93) with 2 more BRAF mutations (45 and 43, respectively, of 91 samples) detected after snapback enrichment. Different EGFR in-frame deletions in the lung samples produced different hairpin T(m)s. CONCLUSIONS: Use of snapback primers for enrichment and detection of minority alleles is simple, is inexpensive to perform, and can be completed in a closed tube in <25 min. PMID- 20299679 TI - Multiplex enzyme assay for galactosemia using ultraperformance liquid chromatography-tandem mass spectrometry. AB - BACKGROUND: Galactosemia is one of the most important inherited disorders detected by newborn screening tests. Abnormal results in screening tests should be confirmed by enzyme activity assays, but existing methods are time and labor intensive. We developed a novel multiplex enzyme assay for galactosemia using ultraperformance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). METHODS: [(13)C6]-galactose, [(13)C2]-galactose-1-phosphate, and UDP-glucose were used as substrates for 3 galactose-metabolizing enzymes. The end products from the combined reaction mixtures, [(13)C6]-galactose-1-phosphate, UDP-[(13)C2] galactose, and UDP-galactose, were simultaneously measured using UPLC-MS/MS. Linearity, imprecision, ion suppression, and the effects of substrate were evaluated to determine assay performance. Enzyme activities from 35 healthy individuals, 8 patients with enzyme deficiency, and 18 mutant cells were analyzed. RESULTS: Substrates, products, and internal standards from the mixture of 3 enzyme reactions were clearly separated by using UPLC-MS/MS, with an injection cycle time of 10 min. Ion suppression was 0.1%-2.5%, the interassay imprecision of UPLC-MS/MS was 3.3%-10.6% CV, and the linearity of each system was good (R(2) = 0.994-0.999). Patient samples and mutated cells showed consistently low enzyme activities compared with those of normal individuals and wild-type cells. CONCLUSIONS: This method allows for a high-throughput and reproducible multiplex enzyme assay for galactosemia in erythrocytes. PMID- 20299680 TI - Liquid chromatography-isotope dilution-mass spectrometry as a new basis for the reference measurement procedure for hemoglobin A1c determination. AB - BACKGROUND: Standardization of hemoglobin (Hb)A(1c) measurements is a process of considerable interest for quality assurance in diabetes management. To contribute to continuous quality improvement and fulfillment of the requirements for reference measurement procedures according to the standards of the International Organization for Standardization, we developed a calibration system of highest metrological order using isotope dilution-mass spectrometry with a reference material. METHOD: Samples were prepared by enzymatic cleavage based on the IFCC reference measurement procedure for LC-MS analysis. After digestion the samples were spiked with [D7]-labeled glycated and nonglycated hexapeptides as internal standards for quantification. LC-MS analysis was performed by using a C12 reversed-phase column and a gradient of acetonitrile/H(2)O containing 0.1% formic acid. RESULTS: Calibration systems for HbA(1c) determination based on liquid chromatography-isotope dilution-mass spectrometry (LC-ID-MS) and on the IFCC reference measurement procedure were compared. A linear regression analysis demonstrated a correlation of r(2) = 1.00 between the 2 different calibration systems. Mean deviation was 5.5% for the calibration and 3.3% for hemolysate samples, with a mean expanded uncertainty of 4.9%. CONCLUSIONS: This LC-ID-MS procedure allows the current IFCC reference measurement procedure for HbA(1c) to be raised to a higher order of accuracy. PMID- 20299681 TI - Long- and short-term effects of tobacco smoking on circulating concentrations of B vitamins. AB - BACKGROUND: Smoking is associated with decreased concentrations of several antioxidant vitamins. We sought to determine the relation between circulating concentrations of selected B vitamins and smoking status, with particular attention to longitudinal associations. METHODS: We used baseline data from 2 B vitamin intervention trials that included 6837 patients with ischemic heart disease. Smoking habits were ascertained by interview. Vitamins and metabolites, including the nicotine metabolite cotinine, were measured in plasma and serum by microbiological assays or gas/liquid chromatography-tandem mass spectrometry. RESULTS: The highest circulating concentrations of folate and pyridoxal 5'phosphate (PLP) and lowest concentrations of total plasma homocysteine, a functional marker of folate status, were observed for self-reported never smokers, followed by self-reported ex-smokers and current smokers (P(trend) < 0.001). Cobalamin and its functional marker methylmalonic acid were not associated with smoking status. Based on their low cotinine concentrations, we were able to identify a group of smokers that had abstained from smoking for 3 days or more. Compared with smokers with high plasma cotinine, smokers with low cotinine had significantly higher circulating concentrations of folate, PLP, and riboflavin (all P < 0.005), and this trend continued for ex-smokers, with increasing time since smoking cessation. CONCLUSIONS: Smoking lowered circulating concentrations of folate, PLP, and riboflavin, but concentrations increased significantly after a few days of smoking cessation. We propose that short-term effects may be related to acute smoking-induced oxidative stress, whereas the longer-lasting effects among ex-smokers may reflect changes in diet and/or restoration of vitamin concentrations in tissue during the first few months to years after smoking cessation. PMID- 20299682 TI - Mycobacterium tuberculosis induces IL-17A responses through TLR4 and dectin-1 and is critically dependent on endogenous IL-1. AB - In the present study, we dissected the pathways that trigger the IL-17A responses by MTB. Dectin-1 and TLR4 were shown to be involved in MTB-induced IL-17A production, and blockade of the NOD2, TLR2, or MR had no effect on IL-17A. The MAPK Erk, known to mediate transcription of IL-1beta mRNA, was strongly involved in the IL-17A production induced by MTB. The intracellular enzymes caspase-1 and serine proteases, which process pro-IL-1beta into the active IL-1beta, were also crucial for the induction of IL-17A. Lastly, the MTB-induced IL-17A response was strongly dependent on signaling through the IL-1R but not the IL-6R pathway. In conclusion, the MTB-induced IL-17A response relies strongly on the endogenous IL 1 pathway and IL-1R signaling. TLR4 and dectin-1 are the main receptors responsible for mediating the signals responsible for IL-17A production by MTB. These findings contribute to a better understanding of the host response to mycobacteria and provide the opportunity to explore potential, novel, therapeutic strategies against TB. PMID- 20299683 TI - Monocyte chemoattractant protein-1 deficiency protects against visceral fat induced atherosclerosis. AB - OBJECTIVE: To determine the role of monocyte chemoattractant protein-1 (Mcp-1) on the progression of visceral fat-induced atherosclerosis. METHODS AND RESULTS: Visceral fat inflammation was induced by transplantation of perigonadal fat. To determine whether recipient Mcp-1 status affected atherosclerosis induced by inflammatory fat, apolipoprotein E-deficient (ApoE(-/-)) and ApoE(-/-) and Mcp-1 deficient (Mcp-1(-/-)) mice underwent visceral fat transplantation. Intravital microscopy was used to study leukocyte-endothelial interactions. To study the primary tissue source of circulating Mcp-1, both fat and bone marrow transplantation experiments were used. Transplantation of visceral fat increased atherosclerosis in ApoE(-/-) mice but had no effect on atherosclerosis in ApoE(-/ ),Mcp-1(-/-) mice. Intravital microscopy revealed increased leukocyte attachment to the endothelium in ApoE(-/-) mice compared with ApoE(-/-),Mcp-1(-/-) mice after receiving visceral fat transplants. Transplantation of visceral fat increased plasma Mcp-1, although donor adipocytes were not the source of circulating Mcp-1 because no Mcp-1 was detected in plasma from ApoE(-/-),Mcp-1(-/ ) mice transplanted with Wt fat, indicating that recipient Mcp-1-producing cells were affecting the atherogenic response to the fat transplantation. Consistently, transplantation of Mcp-1(-/-) fat to ApoE(-/-) mice did not lead to atheroprotection in recipient mice. Bone marrow transplantation between Wt and Mcp-1(-/-) mice indicated that the primary tissue source of circulating Mcp-1 was the endothelium. CONCLUSIONS: Recipient Mcp-1 deficiency protects against atherosclerosis induced by transplanted visceral adipose tissue. PMID- 20299684 TI - Impaired development of atherosclerosis in Abcg1-/- Apoe-/- mice: identification of specific oxysterols that both accumulate in Abcg1-/- Apoe-/- tissues and induce apoptosis. AB - OBJECTIVE: To generate Abcg1(-/-) Apoe(-/-) mice to understand the mechanism and cell types involved in changes in atherosclerosis after loss of ABCG1. METHODS AND RESULTS: ABCG1 is highly expressed in macrophages and endothelial cells, 2 cell types that play important roles in the development of atherosclerosis. Abcg1(-/-) Apoe(-/-) and Apoe(-/-) mice and recipient Apoe(-/-) mice that had undergone transplantation with bone marrow from Apoe(-/-) or Abcg1(-/-) Apoe(-/-) mice were fed a Western diet for 12 or 16 weeks before quantification of atherosclerotic lesions. These studies demonstrated that loss of ABCG1 from all tissues, or from only hematopoietic cells, was associated with significantly smaller lesions that contained increased numbers of TUNEL- and cleaved caspase 3 positive apoptotic Abcg1(-/-) macrophages. We also identified specific oxysterols that accumulate in the brains and macrophages of the Abcg1(-/-) Apoe(-/-) mice. These oxysterols promoted apoptosis and altered the expression of proapoptotic genes when added to macrophages in vitro. CONCLUSIONS: Loss of ABCG1 from all tissues or from only hematopoietic cells results in smaller atherosclerotic lesions populated with increased apoptotic macrophages, by processes independent of ApoE. Specific oxysterols identified in tissues of Abcg1(-/-) Apoe(-/-) mice may be critical because they induce macrophage apoptosis and the expression of proapoptotic genes. PMID- 20299686 TI - Characterization of ion channels involved in the proliferative response of femoral artery smooth muscle cells. AB - OBJECTIVE: Vascular smooth muscle cells (VSMCs) contribute significantly to occlusive vascular diseases by virtue of their ability to switch to a noncontractile, migratory, and proliferating phenotype. Although the participation of ion channels in this phenotypic modulation (PM) has been described previously, changes in their expression are poorly defined because of their large molecular diversity. We obtained a global portrait of ion channel expression in contractile versus proliferating mouse femoral artery VSMCs, and explored the functional contribution to the PM of the most relevant changes that we observed. METHODS AND RESULTS: High-throughput real-time polymerase chain reaction of 87 ion channel genes was performed in 2 experimental paradigms: an in vivo model of endoluminal lesion and an in vitro model of cultured VSMCs obtained from explants. mRNA expression changes showed a good correlation between the 2 proliferative models, with only 2 genes, Kv1.3 and Kvbeta2, increasing their expression on proliferation. The functional characterization demonstrates that Kv1.3 currents increased in proliferating VSMC and that their selective blockade inhibits migration and proliferation. CONCLUSIONS: These findings establish the involvement of Kv1.3 channels in the PM of VSMCs, providing a new therapeutical target for the treatment of intimal hyperplasia. PMID- 20299685 TI - The intrinsic complement regulator decay-accelerating factor modulates the biological response to vascular injury. AB - OBJECTIVE: To investigate whether the presence of decay-accelerating factor (or CD55), an intrinsic complement regulator, protects against the development of vascular disease, given that complement activation can affect leukocytes and platelets. METHODS AND RESULTS: Leukocyte-platelet complexes are critical for the initiation and progression of atherosclerosis and restenosis; however, the mechanism by which these processes promote vascular injury is incompletely defined. We performed femoral artery wire injury in Daf1(-/-) mice and their wild type controls. Leukocyte accumulation, cellular proliferation, and neointimal thickening were enhanced in Daf1(-/-) mice versus wild-type mice. Deficiency of either the C3a or the C5a receptor, respectively, reversed the increased vascular inflammation, cellular proliferation, and neointimal formation in Daf1(-/-) mice. CONCLUSIONS: Decay-accelerating factor control of C3a and C5a generation and prevention of the binding of these activation fragments to the C3a and C5a receptors are critical for the biological response to vascular injury. Targeting the C3a and C5a receptors may be useful for the prevention of neointimal hyperplasia. PMID- 20299687 TI - Aortic regurgitation dramatically alters the distribution of atherosclerotic lesions and enhances atherogenesis in mice. AB - OBJECTIVE: Hemodynamics plays a critical role in atherogenesis, but the association between flow pattern and preferential localization of lesion is not fully understood. We developed a mouse model of aortic valve regurgitation (AR) to change the aortic flow pattern and observed the effects on plaque formation. METHODS AND RESULTS: High-frequency Doppler ultrasound imaging of 10 untreated C57BL/6J mice and 6 sham-treated low-density lipoprotein receptor-deficient (Ldlr(-/-)) mice revealed consistent antegrade blood flow throughout the aorta and oscillatory flow only along the lesser curvature of the aortic arch. Catheter induced AR in 7 Ldlr(-/-) mice produced various degrees of diastolic retrograde flow throughout the aorta. After the mice were fed a cholesterol-enriched diet for 6 weeks, the burden of atherosclerotic lesions was increased 6-fold, with the naturally plaque-resistant descending aorta becoming susceptible. The AR severity correlated positively with the lesion burden in the descending thoracic and abdominal aorta but negatively with the lesions in the ascending aorta and aortic arch. CONCLUSIONS: This AR model is valuable for elucidating the relationship between hemodynamics and predisposition of the artery wall to atherosclerosis, because of the significant alterations in local flow patterns and the conversion of large regions in the descending aorta from lesion resistant to lesion prone. PMID- 20299688 TI - Peripheral artery disease is associated with a high CD163/TWEAK plasma ratio. AB - OBJECTIVE: In addition to its role in the clearance of haptoglobin-hemoglobin (Hp Hb) complexes, CD163 is a macrophage scavenger receptor for tumor necrosis factor like weak inducer of apoptosis (TWEAK). We recently reported that the CD163/TWEAK plasma ratio could be a potential biomarker of atherothrombosis in asymptomatic subjects. In this study, we assessed soluble TWEAK (sTWEAK) and soluble CD163 (sCD163) plasma levels in white males with peripheral artery disease (PAD) and in atherothrombotic femoral plaques to evaluate their relationship with disease. We also analyzed whether Hp-Hb complexes could compete for CD163-mediated TWEAK uptake. METHODS AND RESULTS: Patients with PAD (n=155) showed a trend toward lower sTWEAK (median [interquartile range]: 134 [110-204] versus 147 [119-205] pg/mL; P=0.067) and higher sCD163 (median [interquartile range]: 367 [269-506] versus 288 [234-369] ng/mL; P<0.001) plasma concentrations than age-matched controls (n=251). sCD163 and sTWEAK plasma levels were negatively correlated in both patients and controls. After stratification according to the severity of disease, sCD163/sTWEAK ratio was significantly increased in patients with more severe disease relative to the other groups (P=0.049). Analysis of conditioned medium obtained from cultured human atherothrombotic femoral plaque samples (n=36) and healthy aortas (n=14) revealed that high amounts of sCD163 were released by the atherothrombotic tissue, whereas sTWEAK presented the opposite trend (P<0.05). Finally, we report a potential association between CD163 shedding and oxidative stress. CONCLUSIONS: Our results suggest that the sCD163/sTWEAK plasma ratio may be associated with atherothrombosis burden in PAD. We hypothesize that an imbalance between TWEAK and CD163 could reflect the progression of atherothrombosis. PMID- 20299689 TI - The extent of coronary atherosclerosis is associated with increasing circulating levels of high sensitive cardiac troponin T. AB - OBJECTIVE: This study explored the relationship between coronary atherosclerotic plaque burden and quantifiable circulating levels of troponin measured with a recently introduced high sensitive cardiac troponin T (hs-cTnT) assay. METHODS AND RESULTS: Cardiac patients suspected of having coronary artery disease (CAD) but without acute coronary syndrome were studied. Cardiac troponin T levels were assessed using the fifth-generation hs-cTnT assay. All patients (n=615) underwent cardiac computed tomographic angiography (CCTA). On the basis of CCTA, patients were classified as having no CAD or mild (<50% lesion), moderate (50% to 70% lesion), severe (>70% lesion), or multivessel CAD (multiple >70% lesions). As a comparison, high-sensitivity C-reactive protein levels were measured. Progressively increasing hs-cTnT levels were found in patients with mild (median, 4.5 ng/L), moderate (median, 5.5 ng/L), severe (median, 5.7 ng/L), and multivessel (median, 8.6 ng/L) CAD compared with patients without CAD (median, 3.7 ng/L) (all P<0.01). For high-sensitivity C-reactive protein and N-terminal pro-B-type natriuretic peptide, no such relationship was observed. In patients without CAD, 11% showed hs-cTnT levels in the highest quartile, compared with 62% in the multivessel disease group (P<0.05). Multivariance analysis identified hs cTnT as an independent risk factor for the presence of CAD. CONCLUSIONS: In patients without acute coronary syndrome, even mild CAD is associated with quantifiable circulating levels of hs-cTnT. PMID- 20299690 TI - Vascular endothelial growth factor-secreting mast cells and myofibroblasts: a novel self-perpetuating angiogenic pathway in aortic valve stenosis. AB - OBJECTIVE: To examine the proangiogenic potential of myofibroblasts and mast cells, 2 types of cells present in human aortic valves. METHODS AND RESULTS: Aortic valve stenosis is an active atheroinflammatory disease, characterized by the accumulation of inflammatory cells and the neovascularization of the valves. A total of 85 stenotic valves and 20 control valves were obtained during valve replacement surgery. The results of immunohistochemistry analysis revealed stenotic aortic valves that contained 3 types of neovessels: small microvessels, medium microvessels, and organized arterioles. The distribution density of the neovessels was significantly higher in stenotic valves than in control valves (P<0.001) and correlated positively with valvular calcification gradus (r=0.26, P=0.02) and mast cell density (r=0.38, P<0.001). In the neovascularized areas of stenotic aortic valves, mast cells contained vascular endothelial growth factor and were degranulated, indicating their activation. The stimulation of cultured myofibroblasts derived from aortic valves with a mast cell-preconditioned medium, hypoxic culture conditions, or tobacco smoke all induced vascular endothelial growth factor secretion in the myofibroblasts. Finally, mast cell tryptase was able to degrade the antiangiogenic molecule endostatin in vitro. CONCLUSIONS: Mast cells and myofibroblasts may accelerate the progression of aortic valve stenosis by altering the balance between angiogenic and antiangiogenic factors in the valves, thus promoting valvular neovascularization. PMID- 20299691 TI - Lack of association between adiponectin levels and atherosclerosis in mice. AB - OBJECTIVE: Adiponectin is an adipocyte-derived, secreted protein that is implicated in protection against a cluster of related metabolic disorders. Mice lacking adiponectin display impaired hepatic insulin sensitivity and respond only partially to peroxisome proliferator-activated receptor gamma agonists. Adiponectin has been associated with antiinflammatory and antiatherogenic properties; however, the direct involvement of adiponectin on the atherogenic process has not been studied. METHODS AND RESULTS: We crossed adiponectin knockout mice (Adn(-/-)) or mice with chronically elevated adiponectin levels (Adn(Tg)) into the low-density lipoprotein receptor-null (Ldlr(-/-)) and the apoliprotein E-null (Apoe(-/-)) mouse models. Adiponectin levels did not correlate with a suppression of the atherogenic process. Plaque volume in the aortic root, cholesterol accumulation in the aorta, and plaque morphology under various dietary conditions were not affected by circulating adiponectin levels. In light of the strong associations reported for adiponectin with cardiovascular disease in humans, the lack of a phenotype in gain- and loss-of-function studies in mice suggests a lack of causation for adiponectin in inhibiting the buildup of atherosclerotic lesions. CONCLUSIONS: These data indicate that the actions of adiponectin on the cardiovascular system are complex and multifaceted, with a minimal direct impact on atherosclerotic plaque formation in preclinical rodent models. PMID- 20299693 TI - Critical illness as a result of influenza A/H1N1 infection in pregnancy. PMID- 20299692 TI - Caregiver participation in hospice interdisciplinary team meetings via videophone technology: A pilot study to improve pain management. AB - This article discusses a pilot study testing a videophone intervention enabling hospice patients and caregivers to remotely participate in interdisciplinary team meetings, with the goal of improving pain management. The aim of this study was to test potential outcome measures and combine the data with qualitative observations to assess the overall feasibility and promise of the intervention. The outcomes evaluated included hospice patient quality of life, caregiver perceptions of pain medications, caregiver quality of life, and caregiver anxiety related to team participation. The pilot study showed that caregiver participation in the care planning process is feasible and may change caregiver perceptions of pain medication, potentially improving pain management for hospice patients. PMID- 20299695 TI - Acupuncture transmitted infections. PMID- 20299694 TI - Critical illness due to 2009 A/H1N1 influenza in pregnant and postpartum women: population based cohort study. AB - OBJECTIVE: To describe the epidemiology of 2009 A/H1N1 influenza in critically ill pregnant women. DESIGN: Population based cohort study. SETTING: All intensive care units in Australia and New Zealand. PARTICIPANTS: All women with 2009 H1N1 influenza who were pregnant or recently post partum and admitted to an intensive care unit in Australia or New Zealand between 1 June and 31 August 2009. MAIN OUTCOME MEASURES: Maternal and neonatal mortality and morbidity. RESULTS: 64 pregnant or postpartum women admitted to an intensive care unit had confirmed 2009 H1N1 influenza. Compared with non-pregnant women of childbearing age, pregnant or postpartum women with 2009 H1N1 influenza were at increased risk of admission to an intensive care unit (relative risk 7.4, 95% confidence interval 5.5 to 10.0). This risk was 13-fold greater (13.2, 9.6 to 18.3) for women at 20 or more weeks' gestation. At the time of admission to an intensive care unit, 22 women (34%) were post partum and two had miscarried. 14 women (22%) gave birth during their stay in intensive care and 26 (41%) were discharged from an intensive care unit with ongoing pregnancy. All subsequently delivered. 44 women (69%) were mechanically ventilated. Of these, nine (14%) were treated with extracorporeal membrane oxygenation. Seven women (11%) died. Of 60 births after 20 weeks' gestation, four were stillbirths and three were infant deaths. 22 (39%) of the liveborn babies were preterm and 32 (57%) were admitted to a neonatal intensive care unit. Of 20 babies tested, two were positive for the 2009 H1N1 virus. CONCLUSIONS: Pregnancy is a risk factor for critical illness related to 2009 H1N1 influenza, which causes maternal and neonatal morbidity and mortality. PMID- 20299696 TI - Association between industry affiliation and position on cardiovascular risk with rosiglitazone: cross sectional systematic review. AB - OBJECTIVE: To explore a possible link between authors' financial conflicts of interest and their position on the association of rosiglitazone with increased risk of myocardial infarction in patients with diabetes. DATA SOURCES: On 10 April 2009, we searched Web of Science and Scopus for articles citing and commenting on either of two index publications that contributed key data to the controversy (a meta-analysis of small trials and a subsequent large trial). Data selection Articles had to comment on rosiglitazone and the risk of myocardial infarction. Guidelines, meta-analyses, reviews, clinical trials, letters, commentaries, and editorials were included. DATA EXTRACTION: For each article, we sought information about the authors' financial conflicts of interest in the report itself and elsewhere (that is, in all publications within two years of the original publication and online). Two reviewers blinded to the authors' financial relationships independently classified each article as presenting a favourable (that is, rosiglitazone does not increase the risk of myocardial infarction), neutral, or unfavourable view on the risk of myocardial infarction with rosiglitazone and on recommendations on the use of the drug. RESULTS: Of the 202 included articles, 108 (53%) had a conflict of interest statement. Ninety authors (45%) had financial conflicts of interest. Authors who had a favourable view of the risk of myocardial infarction with rosiglitazone were more likely to have financial conflicts of interest with manufacturers of antihyperglycaemic agents in general, and with rosiglitazone manufacturers in particular, than authors who had an unfavourable view (rate ratio 3.38, 95% CI 2.26 to 5.06 and 4.29, 2.63 to 7.02, respectively). There was likewise a strong association between favourable recommendations on the use of rosiglitazone and financial conflicts of interest (3.36, 1.94 to 5.83). These links persisted when articles rather than authors were used as the unit of analysis (4.69, 2.84 to 7.72), when the analysis was restricted to opinion articles (6.29, 2.15 to 18.38) or to articles in which the rosiglitazone controversy was the main focus (6.50, 2.56 to 16.53), and both in articles published before and after the Food and Drug Administration issued a safety warning for rosiglitazone (3.43, 0.99 to 11.82 and 4.95, 2.87 to 8.53, respectively). CONCLUSIONS: Disclosure rates for financial conflicts of interest were unexpectedly low, and there was a clear and strong link between the orientation of authors' expressed views on the rosiglitazone controversy and their financial conflicts of interest with pharmaceutical companies. Although these findings do not necessarily indicate a causal link between the position taken on the cardiac risk of rosiglitazone in patients with diabetes and the authors' financial conflicts of interest, they underscore the need for further changes in disclosure procedures in order for the scientific record to be trusted. PMID- 20299697 TI - Developmental and functional abilities in children with cerebral palsy as related to pattern and level of motor function. AB - Abilities among school-aged children with cerebral palsy with different patterns and levels of motor function were evaluated. Children within spasticity patterns (33 with quadriplegia, 25 with hemiplegia, 19 with diplegia) and Gross Motor Function Classification System levels were compared (level I, walking = 47%; level II-III, restricted ambulation = 18%; level IV-V, wheelchair needs = 34%,). Outcomes included measures of intelligence, behavior, motor, and functional limitations (communication, daily living, socialization). Motor performance and prosocial behaviors were lower for children with quadriplegia (F = 16.13, 12.71; P < .0001), with no differences for behavioral difficulties between spasticity groups. Prosocial behaviors were different between level IV-V and other groups (F = 16.25, P < .0001). Functional limitations were more likely for children with quadriplegia (P < .0001), but not diplegia or hemiplegia, and for children in level IV-V, but similar for level I and level II-III. Children with quadriplegia, or level IV-V, are more likely to exhibit limitations, whereas children with better motor function (I-III), hemiplegia, or diplegia, exhibit diverse capabilities. A holistic assessment approach is essential to ensure that limitations are addressed comprehensively. PMID- 20299698 TI - Spinal cord infarction due to fibrocartilaginous embolization: the role of diffusion weighted imaging and short-tau inversion recovery sequences. AB - Fibrocartilaginous embolization is a rare cause of ischemic myelopathy caused by embolization of intersomatic disk nucleus pulposus into spinal vasculature during Valsalva-like maneuvers. Diagnostic criteria are based on patient's clinical history, magnetic resonance evidence of T2-hyperintense spinal cord lesion, and exclusion of other causes of ischemic myelopathy. These criteria do not take into account the development of magnetic resonance techniques able to enhance signal abnormalities within the neighboring intersomatic disc or vertebral body and to early characterize central nervous system lesions according to the presence of cytotoxic edema. We present 2 pediatric cases of progressive paraplegia attributed to fibrocartilaginous embolization in which short-tau inversion recovery and diffusion-weighted imaging sequences played a pivotal role showing the ischemic nature of spinal cord lesions. Due to its specificity, diffusion weighted imaging should be included in the magnetic resonance criteria of fibrocartilaginous embolization and in standard magnetic resonance analysis when dealing with acute transverse myelopathy. PMID- 20299699 TI - Schizencephaly: pre- and postnatal magnetic resonance imaging. AB - Schizencephaly is a rare disorder of neuronal migration that is characterized by the presence of clefts that extend from the ependymal surface of the lateral ventricles to the pial lining of the cortex. The authors present the case of a female patient with a prenatal diagnosis made by magnetic resonance imaging (MRI), her clinical course, and neurorradiological evolution following birth. A 6 year-old female, with right open lip schizencephaly, was diagnosed by means of prenatal cerebral magnetic resonance at the gestational age of 25 weeks. The patient does not present intellectual disability, reaching developmental mile stones at normal time points. The MRI of the brain reveals right, perisylvian, closed lip schizencephaly. Prenatal MRI is remarkably useful in the diagnosis and prognostic approach to the condition. It is less useful in classifying the unilateral forms (open vs closed lips), and hence, its prognostic validity is more limited. PMID- 20299701 TI - Growth differentiation factor-15 and cardiovascular dysfunction and disease: malefactor or innocent bystander? PMID- 20299700 TI - Electroencephalogram discharges in atypical cognitive development. AB - To investigate the significance of electroencephalogram (EEG) discharges and their treatment, we retrospectively reviewed the charts of 22 children with atypical cognitive development that did not respond to standard educational therapy and demonstrated discharges on EEG. Most children demonstrated no obvious symptoms of seizures, and developmental regression and/or fluctuations were uncommon. The majority of children demonstrated a language and attention disorder and autism symptomatology and had multifocal discharges on EEGs. Of the 20 patients treated with antiepileptic medications, 70% demonstrated definite improvement within 1 clinic visit. This study suggests that children with EEG discharges and developmental cognitive disorders demonstrate a unique pattern of symptomatology and discharges on EEG. This study suggests that children with developmental cognitive disorders that do not respond to standard therapy may benefit from screening with an EEG and a trial of antiepileptic mediation if discharges are detected. PMID- 20299702 TI - Stroke risk in AF: do AF patterns matter? PMID- 20299704 TI - Domain adaptation problems: a DASVM classification technique and a circular validation strategy. AB - This paper addresses pattern classification in the framework of domain adaptation by considering methods that solve problems in which training data are assumed to be available only for a source domain different (even if related) from the target domain of (unlabeled) test data. Two main novel contributions are proposed: 1) a domain adaptation support vector machine (DASVM) technique which extends the formulation of support vector machines (SVMs) to the domain adaptation framework and 2) a circular indirect accuracy assessment strategy for validating the learning of domain adaptation classifiers when no true labels for the target- domain instances are available. Experimental results, obtained on a series of two dimensional toy problems and on two real data sets related to brain computer interface and remote sensing applications, confirmed the effectiveness and the reliability of both the DASVM technique and the proposed circular validation strategy. PMID- 20299703 TI - Regression of advanced rat and human gliomas by local or systemic treatment with oncolytic parvovirus H-1 in rat models. AB - Oncolytic virotherapy is a potential treatment modality under investigation for various malignancies including malignant brain tumors. Unlike some other natural or modified viruses that show oncolytic activity against cerebral neoplasms, the rodent parvovirus H-1 (H-1PV) is completely apathogenic in humans. H-1PV efficiently kills a number of tumor cells without harm to corresponding normal ones. In this study, the concept of H-1PV-based virotherapy of glioma was tested for rat (RG-2 cell-derived) and for human (U87 cell-derived) gliomas in immunocompetent and immunodeficient rat models, respectively. Large orthotopic rat and human glioma cell-derived tumors were treated with either single stereotactic intratumoral or multiple intravenous (iv) H-1PV injections. Oncolysis was monitored by magnetic resonance imaging and proven by histology. Virus distribution and replication were determined in brain and organs. In immunocompetent rats bearing RG-2-derived tumors, a single stereotactic intratumoral injection of H-1PV and multiple systemic (iv) applications of the virus were sufficient for remission of advanced and even symptomatic intracranial gliomas without damaging normal brain tissue or other organs. H-1PV therapy resulted in significantly improved survival (Kaplan-Meier analysis) in both the rat and human glioma models. Virus replication in tumors indicated a contribution of secondary infection by progeny virus to the efficiency of oncolysis. Virus replication was restricted to tumors, although H-1PV DNA could be detected transiently in adjacent or remote normal brain tissue and in noncerebral tissues. The results presented here and the innocuousness of H-1PV for humans argue for the use of H-1PV as a powerful means to perform oncolytic therapy of malignant gliomas. PMID- 20299705 TI - Sparse multiple kernel learning for signal processing applications. AB - In many signal processing applications, grouping of features during model development and the selection of a small number of relevant groups can be useful to improve the interpretability of the learned parameters. While a lot of work based on linear models has been reported to solve this problem, in the last few years, multiple kernel learning has come up as a candidate to solve this problem in nonlinear models. Since all of the multiple kernel learning algorithms to date use convex primal problem formulations, the kernel weights selected by these algorithms are not strictly the sparsest possible solution. The main reason for using a convex primal formulation is that efficient implementations of kernel based methods invariably rely on solving the dual problem. This work proposes the use of an additional log-based concave penalty term in the primal problem to induce sparsity in terms of groups of parameters. A generalized iterative learning algorithm, which can be used with a linear combination of this concave penalty term with other penalty terms, is given for model parameter estimation in the primal space. It is then shown that a natural extension of the method to nonlinear models using the "kernel trick" results in a new algorithm, called Sparse Multiple Kernel Learning (SMKL), which generalizes group-feature selection to kernel selection. SMKL is capable of exploiting existing efficient single kernel algorithms while providing a sparser solution in terms of the number of kernels used as compared to the existing multiple kernel learning framework. A number of signal processing examples based on the use of mass spectra for cancer detection, hyperspectral imagery for land cover classification, and NIR spectra from wheat, fescue grass, and diesel are given to highlight the ability of SMKL to achieve a very high accuracy with a very few kernels. PMID- 20299706 TI - A general methodology for the determination of 2D bodies elastic deformation invariants: application to the automatic identification of parasites. AB - A novel methodology is introduced here that exploits 2D images of arbitrary elastic body deformation instances so as to quantify mechanoelastic characteristics that are deformation invariant. Determination of such characteristics allows for developing methods offering an image of the undeformed body. General assumptions about the mechanoelastic properties of the bodies are stated which lead to two different approaches for obtaining bodies' deformation invariants. One was developed to spot a deformed body's neutral line and its cross sections, while the other solves deformation PDEs by performing a set of equivalent image operations on the deformed body images. Both of these processes may furnish a body-undeformed version from its deformed image. This was confirmed by obtaining the undeformed shape of deformed parasites, cells (protozoa), fibers, and human lips. In addition, the method has been applied to the important problem of parasite automatic classification from their microscopic images. To achieve this, we first apply the previous method to straighten the highly deformed parasites, and then, apply a dedicated curve classification method to the straightened parasite contours. It is demonstrated that essentially different deformations of the same parasite give rise to practically the same undeformed shape, thus confirming the consistency of the introduced methodology. Finally, the developed pattern recognition method classifies the unwrapped parasites into six families, with an accuracy rate of 97.6 percent. PMID- 20299707 TI - DAISY: an efficient dense descriptor applied to wide-baseline stereo. AB - In this paper, we introduce a local image descriptor, DAISY, which is very efficient to compute densely. We also present an EM-based algorithm to compute dense depth and occlusion maps from wide-baseline image pairs using this descriptor. This yields much better results in wide-baseline situations than the pixel and correlation-based algorithms that are commonly used in narrow-baseline stereo. Also, using a descriptor makes our algorithm robust against many photometric and geometric transformations. Our descriptor is inspired from earlier ones such as SIFT and GLOH but can be computed much faster for our purposes. Unlike SURF, which can also be computed efficiently at every pixel, it does not introduce artifacts that degrade the matching performance when used densely. It is important to note that our approach is the first algorithm that attempts to estimate dense depth maps from wide-baseline image pairs, and we show that it is a good one at that with many experiments for depth estimation accuracy, occlusion detection, and comparing it against other descriptors on laser-scanned ground truth scenes. We also tested our approach on a variety of indoor and outdoor scenes with different photometric and geometric transformations and our experiments support our claim to being robust against these. PMID- 20299708 TI - FRVT 2006 and ICE 2006 large-scale experimental results. AB - This paper describes the large-scale experimental results from the Face Recognition Vendor Test (FRVT) 2006 and the Iris Challenge Evaluation (ICE) 2006. The FRVT 2006 looked at recognition from high-resolution still frontal face images and 3D face images, and measured performance for still frontal face images taken under controlled and uncontrolled illumination. The ICE 2006 evaluation reported verification performance for both left and right irises. The images in the ICE 2006 intentionally represent a broader range of quality than the ICE 2006 sensor would normally acquire. This includes images that did not pass the quality control software embedded in the sensor. The FRVT 2006 results from controlled still and 3D images document at least an order-of-magnitude improvement in recognition performance over the FRVT 2002. The FRVT 2006 and the ICE 2006 compared recognition performance from high-resolution still frontal face images, 3D face images, and the single-iris images. On the FRVT 2006 and the ICE 2006 data sets, recognition performance was comparable for high-resolution frontal face, 3D face, and the iris images. In an experiment comparing human and algorithms on matching face identity across changes in illumination on frontal face images, the best performing algorithms were more accurate than humans on unfamiliar faces. PMID- 20299709 TI - Kernel entropy component analysis. AB - We introduce kernel entropy component analysis (kernel ECA) as a new method for data transformation and dimensionality reduction. Kernel ECA reveals structure relating to the Renyi entropy of the input space data set, estimated via a kernel matrix using Parzen windowing. This is achieved by projections onto a subset of entropy preserving kernel principal component analysis (kernel PCA) axes. This subset does not need, in general, to correspond to the top eigenvalues of the kernel matrix, in contrast to the dimensionality reduction using kernel PCA. We show that kernel ECA may produce strikingly different transformed data sets compared to kernel PCA, with a distinct angle-based structure. A new spectral clustering algorithm utilizing this structure is developed with positive results. Furthermore, kernel ECA is shown to be an useful alternative for pattern denoising. PMID- 20299710 TI - Learning context-sensitive shape similarity by graph transduction. AB - Shape similarity and shape retrieval are very important topics in computer vision. The recent progress in this domain has been mostly driven by designing smart shape descriptors for providing better similarity measure between pairs of shapes. In this paper, we provide a new perspective to this problem by considering the existing shapes as a group, and study their similarity measures to the query shape in a graph structure. Our method is general and can be built on top of any existing shape similarity measure. For a given similarity measure, a new similarity is learned through graph transduction. The new similarity is learned iteratively so that the neighbors of a given shape influence its final similarity to the query. The basic idea here is related to PageRank ranking, which forms a foundation of Google Web search. The presented experimental results demonstrate that the proposed approach yields significant improvements over the state-of-art shape matching algorithms. We obtained a retrieval rate of 91.61 percent on the MPEG-7 data set, which is the highest ever reported in the literature. Moreover, the learned similarity by the proposed method also achieves promising improvements on both shape classification and shape clustering. PMID- 20299711 TI - Nonnegative least-correlated component analysis for separation of dependent sources by volume maximization. AB - Although significant efforts have been made in developing nonnegative blind source separation techniques, accurate separation of positive yet dependent sources remains a challenging task. In this paper, a joint correlation function of multiple signals is proposed to reveal and confirm that the observations after nonnegative mixing would have higher joint correlation than the original unknown sources. Accordingly, a new nonnegative least-correlated component analysis (n/LCA) method is proposed to design the unmixing matrix by minimizing the joint correlation function among the estimated nonnegative sources. In addition to a closed-form solution for unmixing two mixtures of two sources, the general algorithm of n/LCA for the multisource case is developed based on an iterative volume maximization (IVM) principle and linear programming. The source identifiability and required conditions are discussed and proven. The proposed n/LCA algorithm, denoted by n/LCA-IVM, is evaluated with both simulation data and real biomedical data to demonstrate its superior performance over several existing benchmark methods. PMID- 20299712 TI - Polynomial time algorithms for ratio regions and a variant of normalized cut. AB - In partitioning, clustering, and grouping problems, a typical goal is to group together similar objects, or pixels in the case of image processing. At the same time, another goal is to have each group distinctly dissimilar from the rest and possibly to have the group size fairly large. These goals are often combined as a ratio optimization problem. One example of such a problem is a variant of the normalized cut problem, another is the ratio regions problem. We devise here the first polynomial time algorithms solving optimally the ratio region problem and the variant of normalized cut, as well as a few other ratio problems. The algorithms are efficient and combinatorial, in contrast with nonlinear continuous approaches used in the image segmentation literature, which often employ spectral techniques. Such techniques deliver solutions in real numbers which are not feasible to the discrete partitioning problem. Furthermore, these continuous approaches are computationally expensive compared to the algorithms proposed here. The algorithms presented here use as a subroutine a minimum s,t-cut procedure on a related graph which is of polynomial size. The output consists of the optimal solution to the respective ratio problem, as well as a sequence of nested solutions with respect to any relative weighting of the objectives of the numerator and denominator. PMID- 20299713 TI - Spatial-temporal fusion for high accuracy depth maps using dynamic MRFs. AB - Time-of-flight range sensors and passive stereo have complimentary characteristics in nature. To fuse them to get high accuracy depth maps varying over time, we extend traditional spatial MRFs to dynamic MRFs with temporal coherence. This new model allows both the spatial and the temporal relationship to be propagated in local neighbors. By efficiently finding a maximum of the posterior probability using Loopy Belief Propagation, we show that our approach leads to improved accuracy and robustness of depth estimates for dynamic scenes. PMID- 20299714 TI - Unsupervised object segmentation with a hybrid graph model (HGM). AB - In this work, we address the problem of performing class-specific unsupervised object segmentation, i.e., automatic segmentation without annotated training images. Object segmentation can be regarded as a special data clustering problem where both class-specific information and local texture/color similarities have to be considered. To this end, we propose a hybrid graph model (HGM) that can make effective use of both symmetric and asymmetric relationship among samples. The vertices of a hybrid graph represent the samples and are connected by directed edges and/or undirected ones, which represent the asymmetric and/or symmetric relationship between them, respectively. When applied to object segmentation, vertices are superpixels, the asymmetric relationship is the conditional dependence of occurrence, and the symmetric relationship is the color/texture similarity. By combining the Markov chain formed by the directed subgraph and the minimal cut of the undirected subgraph, the object boundaries can be determined for each image. Using the HGM, we can conveniently achieve simultaneous segmentation and recognition by integrating both top-down and bottom up information into a unified process. Experiments on 42 object classes (9,415 images in total) show promising results. PMID- 20299715 TI - Watershed cuts: thinnings, shortest path forests, and topological watersheds. AB - We recently introduced watershed cuts, a notion of watershed in edge-weighted graphs. In this paper, our main contribution is a thinning paradigm from which we derive three algorithmic watershed cut strategies: The first one is well suited to parallel implementations, the second one leads to a flexible linear-time sequential implementation, whereas the third one links the watershed cuts and the popular flooding algorithms. We state that watershed cuts preserve a notion of contrast, called connection value, on which several morphological region merging methods are (implicitly) based. We also establish the links and differences between watershed cuts, minimum spanning forests, shortest path forests, and topological watersheds. Finally, we present illustrations of the proposed framework to the segmentation of artwork surfaces and diffusion tensor images. PMID- 20299716 TI - Decoupled linear estimation of affine geometric deformations and nonlinear intensity transformations of images. AB - We consider the problem of registering two observations on an arbitrary object, where the two are related by a geometric affine transformation of their coordinate systems, and by a nonlinear mapping of their intensities. More generally, the framework is that of jointly estimating the geometric and radiometric deformations relating two observations on the same object. We show that the original high-dimensional, nonlinear, and nonconvex search problem of simultaneously recovering the geometric and radiometric deformations can be represented by an equivalent sequence of two linear systems. A solution of this sequence yields an exact, explicit, and efficient solution to the joint estimation problem. PMID- 20299717 TI - Age-invariant face recognition. AB - One of the challenges in automatic face recognition is to achieve temporal invariance. In other words, the goal is to come up with a representation and matching scheme that is robust to changes due to facial aging. Facial aging is a complex process that affects both the 3D shape of the face and its texture (e.g., wrinkles). These shape and texture changes degrade the performance of automatic face recognition systems. However, facial aging has not received substantial attention compared to other facial variations due to pose, lighting, and expression. We propose a 3D aging modeling technique and show how it can be used to compensate for the age variations to improve the face recognition performance. The aging modeling technique adapts view-invariant 3D face models to the given 2D face aging database. The proposed approach is evaluated on three different databases (i.g., FG-NET, MORPH, and BROWNS) using FaceVACS, a state-of-the-art commercial face recognition engine. PMID- 20299718 TI - Recognition of 3D objects based on implicit polynomials. AB - Closed-form expressions for a new set of 3D rotation invariants that are linear, quadratic, and angular combinations of implicit polynomial (IP) coefficients are developed. Based on these invariants, we propose a 3D object recognition method that outperforms recognition based on IP fitting after pose estimation, and the MPEG-7 SSD technique. PMID- 20299719 TI - Vascular structure and binomial statistics for response modeling in radiosurgery of cerebral arteriovenous malformations. AB - Radiation treatment of arteriovenous malformations (AVMs) has a slow and progressive vaso-occlusive effect. Some studies suggested the possible role of vascular structure in this process. A detailed biomathematical model has been used, where the morphological, biophysical and hemodynamic characteristics of intracranial AVM vessels are faithfully reproduced. The effect of radiation on plexiform and fistulous AVM nidus vessels was simulated using this theoretical model. The similarities between vascular and electrical networks were used to construct this biomathematical AVM model and provide an accurate rendering of transnidal and intranidal hemodynamics. The response of different vessels to radiation and their obliteration probability as a function of different angiostructures were simulated and total obliteration was defined as the probability of obliteration of all possible vascular pathways. The dose response of the whole AVM is observed to depend on the vascular structure of the intra nidus AVM. Furthermore, a plexiform AVM appears to be more prone to obliteration compared with an AVM of the same size but having more arteriovenous fistulas. Finally, a binomial model was introduced, which considers the number of crucial vessels and is able to predict the dose response behavior of AVMs with a complex vascular structure. PMID- 20299720 TI - Photon-counting spectral computed tomography using silicon strip detectors: a feasibility study. AB - We show how the spectral imaging framework should be modified to account for a high fraction of Compton interactions in low Z detector materials such as silicon. Using this framework, where deposited energies differ from actual photon energies, we compare the performance of a silicon strip detector, including the influence of scatter inside the detector and charge sharing but disregarding signal pileup, with an ideal energy integrating detector. We show that although the detection efficiency for silicon rapidly drops for the acceleration voltages encountered in clinical computed tomography practice, silicon detectors could perform on a par with ideal energy integrating detectors for routine imaging tasks. The use of spectrally sensitive detectors opens up the possibility for decomposition techniques such as k-edge imaging, and we show that the proposed modification of the spectral imaging framework is beneficial for such imaging tasks. PMID- 20299721 TI - Ultrasonic particle image velocimetry for improved flow gradient imaging: algorithms, methodology and validation. AB - This paper presents a new algorithm for ultrasonic particle image velocimetry (Echo PIV) for improving the flow velocity measurement accuracy and efficiency in regions with high velocity gradients. The conventional Echo PIV algorithm has been modified by incorporating a multiple iterative algorithm, sub-pixel method, filter and interpolation method, and spurious vector elimination algorithm. The new algorithms' performance is assessed by analyzing simulated images with known displacements, and ultrasonic B-mode images of in vitro laminar pipe flow, rotational flow and in vivo rat carotid arterial flow. Results of the simulated images show that the new algorithm produces much smaller bias from the known displacements. For laminar flow, the new algorithm results in 1.1% deviation from the analytically derived value, and 8.8% for the conventional algorithm. The vector quality evaluation for the rotational flow imaging shows that the new algorithm produces better velocity vectors. For in vivo rat carotid arterial flow imaging, the results from the new algorithm deviate 6.6% from the Doppler measured peak velocities averagely compared to 15% of that from the conventional algorithm. The new Echo PIV algorithm is able to effectively improve the measurement accuracy in imaging flow fields with high velocity gradients. PMID- 20299722 TI - Pixel-based subsets for rapid multi-pinhole SPECT reconstruction. AB - Block-iterative image reconstruction methods, such as ordered subset expectation maximization (OSEM), are commonly used to accelerate image reconstruction. In OSEM, the speed-up factor over maximum likelihood expectation maximization (MLEM) is approximately equal to the number of subsets in which the projection data are divided. Traditionally, each subset consists of a couple of projection views, and the more subsets are used, the more the solution deviates from MLEM solutions. We found for multi-pinhole single photon emission computed tomography (SPECT) that even moderate acceleration factors in OSEM lead to inaccurate reconstructions. Therefore, we introduce pixel-based ordered subset expectation maximization (POSEM), which is based on an alternative subset choice. Pixels in each subset are spread out regularly over projections and are spatially separated as much as possible. We validated POSEM for data acquired with a focusing multi-pinhole SPECT system. Performance was compared with traditional OSEM and MLEM for a rat total body bone scan, a gated mouse myocardial perfusion scan and a Defrise phantom scan. We found that POSEM can be operated at acceleration factors that are often an order of magnitude higher than in traditional OSEM. PMID- 20299723 TI - Thickness-dependent spontaneous dewetting morphology of ultrathin Ag films. AB - We show here that the morphological pathway of spontaneous dewetting of ultrathin Ag films on SiO2 under nanosecond laser melting is dependent on film thickness. For films with thickness h of 2 nm < or = h < or = 9.5 nm, the morphology during the intermediate stages of dewetting consisted of bicontinuous structures. For films with 11.5 nm < or = h < or = 20 nm, the intermediate stages consisted of regularly sized holes. Measurement of the characteristic length scales for different stages of dewetting as a function of film thickness showed a systematic increase, which is consistent with the spinodal dewetting instability over the entire thickness range investigated. This change in morphology with thickness is consistent with observations made previously for polymer films (Sharma and Khanna 1998 Phys. Rev. Lett. 81 3463-6; Seemann et al 2001 J. Phys.: Condens. Matter 13 4925-38). Based on the behavior of free energy curvature that incorporates intermolecular forces, we have estimated the morphological transition thickness for the intermolecular forces for Ag on SiO2. The theory predictions agree well with observations for Ag. These results show that it is possible to form a variety of complex Ag nanomorphologies in a consistent manner, which could be useful in optical applications of Ag surfaces, such as in surface enhanced Raman sensing. PMID- 20299725 TI - Scattering matrix approach to multichannel transport in many lead graphene nanoribbons. AB - Multichannel analysis of graphene nanoribbons (GNR), often required for describing applications to practical devices, constitutes a heavy computational task, even in a simplified framework like that provided by discrete or nearest neighbour models. Scattering (S) matrix techniques, widely used for quantum transport in low dimensional systems and for the computation of electromagnetic fields, is shown here to provide a powerful formal platform for the analysis, and, in principle, the synthesis, of GNR multiport circuits. Periodic modes, solutions of GNR waveguides, are demonstrated to obey charge conservation and reciprocity constraints corresponding to unitary and symmetry properties of the S matrix, under proper normalization conditions. We propose a systematic use of this approach to deal with problems such as scattering by lattice defects, the presence of external applied fields, crossing GNRs and T-junctions. PMID- 20299724 TI - Enzyme-assisted formation of nanosphere: a potential carrier for hydrophobic compounds. AB - In this study, we report the use of a phosphatase to catalyze the formation of nanospheres from a hydrophobic compound (Ada-GFFY-OMe, 2) via a unique mechanism. The nanospheres were stable in aqueous solutions for two weeks. Their size could be controlled by both concentrations of the precursor (Ada-GFFY(p)-OMe, 1) and the enzyme and the nanospheres were characterized by SEM and dynamic light scattering (DLS). We then demonstrated that nanospheres could help the cell impermeable propidium iodine (PI) to penetrate the cells, which implied that the nanospheres have the potential to be developed into useful carriers for hydrophobic drugs. This study offers the first example of using an enzyme to control the formation of nanospheres from a hydrophobic compound. There is thus the potential that nanospheres can be developed into a carrier for hydrophobic drugs. PMID- 20299726 TI - Magnetic carbon nanotube labelling for haematopoietic stem/progenitor cell tracking. AB - Haematopoietic stem and progenitor cell (HSPC) research has significantly contributed to the understanding and harnessing of haematopoiesis for regenerative medicine. However, the methodology for real-time tracking HSPC in vivo is still lacking, which seriously restricts the progress of research. Recently, magnetic carbon nanotubes (mCNT) have generated great excitement because they have been successfully used as vehicles to deliver a lot of biomolecules into various cells. There is, however, no report about mCNT being used for tracking HSPC. In this paper, we investigated the uptake efficiency of fluorescein-isothiocyanate-labelled mCNT (FITC-mCNT) into HSPC and their effect on the cytotoxicity and differentiation of HSPC. We found that cellular uptake of FITC-mCNT was concentration-and time-dependent. The uptake of FITC-mCNT into HSPC reached up to 100% with the highest mean fluorescence (MF). More importantly, efficient FITC-mCNT uptake has no adverse effect on the cell viability, cytotoxicity and differentiation of HSPC as confirmed by colony-forming unit assay (CFU). In conclusion, the results reported here suggest the further tailoring of mCNT for their use in HSPC labelling/tracking in vivo or gene delivery into HSPC. PMID- 20299727 TI - Sensitivity enhancement of differential splitter-based transduction for photonic microcantilever arrays. AB - We report enhanced sensitivity for in-plane photonic transduction of static deflection of microscale cantilevers by modifying the mode structure of double step rib waveguides used to capture light from the free end of waveguide microcantilevers. A measured sensitivity of 0.77 x 10( - 3) nm( - 1) is achieved, comparable to the best reported for the optical lever method and over two orders of magnitude larger than for piezoresistive transduction. The corresponding minimum detectable deflection is 59 pm for a 3.5 Hz measurement bandwidth. PMID- 20299728 TI - Donor-acceptor alternating copolymers as donor materials for bulk-heterojunction solar cells: effects of molecular structure on film morphology and device performance. AB - Three photovoltaic-applicable donor-acceptor (D-A) alternating copolymers including poly{(9,9-dihexyl-9H-fluorene-2,7-ylene)-alt-2-(2,6-bis((E)-2-(5-bromo 3,4-dihexylthiophen-2-yl)vinyl)-4H-pyran-4-ylidene) malononitrile} (PFTMT), poly{(10-hexyl-10H-phenothiazine-3,7-ylene)-alt-2-(2,6-bis((E)-2-(5-bromo-3,4 dihexylthiophen-2-yl)vinyl)-4H-pyran-4-ylidene) malononitrile} (PPTMT) and poly{(2,20-bithiophene-5,50-ylene)-alt-2-(2,6-bis((E)-2-(5-bromo-3,4 dihexylthiophen-2-yl)vinyl)-4H-pyran-4-ylidene)malononitrile} (PDTTMT), were blended with [6,6]-phenyl-C(61)-butyric acid methyl ester (PCBM) to serve as active layers for photovoltaic applications. The effects of extrinsic (blend ratio and solvent) and intrinsic factors (donor materials) on the morphologies of this series of active layers were investigated by atomic force microscopy (AFM) and transmission electron microscopy (TEM). It was found that the PFTMT:PCBM active layers show distinct phase segregation with large PCBM clusters above 100 nm and are strongly affected by solvent evaporation rate in higher blend ratios. In contrast, the PPTMT:PCBM active layers are homogeneous and not affected by blend ratios and solvents, while the PDTTMT:PCBM active layers show an interpenetrating network initially formed at the blend ratio of 1:1. These results indicate that the polymer-PCBM repulsions arising from the molecular structure of the polymers play a significant role in determining the resulting morphologies of the blend films. Strong PFTMT-PCBM repulsion leads to large-scale phase segregation, while weak repulsions in PPTMT-PCBM and PDTTMT-PCBM favor small-scale phase segregation only. The best photovoltaic power conversion efficiencies are obtained from PDTTMT-based solar cells with the PDTTMT:PCBM blend ratio of 1:3 and nanoscale phase separation of the active layer, where a good balance is formed between a large donor-acceptor interface and the continuous paths of donor and acceptor phase for opposite charge carrier transport to their corresponding electrodes. PMID- 20299729 TI - Extended-area nanostructuring of TiO2 with femtosecond laser pulses at 400 nm using a line focus. AB - An efficient way to generate nanoscale laser-induced periodic surface structures (LIPSS) in rutile-type TiO(2) with frequency-converted femtosecond laser pulses at wavelengths around 400 nm is reported. Extended-area structuring on fixed and moving substrates was obtained by exploiting the line focus of a cylindrical lens. Under defined conditions with respect to pulse number, pulse energy and scanning velocity, two types of ripple-like LIPSS with high and low spatial frequencies (HSFL, LSFL) with periods in the range of 90 nm and 340 nm, respectively, were formed. In particular, lower numbers of high energetic pulses favour the generation of LSFL whereas higher numbers of lower energetic pulses enable the preferential creation of HSFL. Theoretical calculations on the basis of the Drude model support the assumption that refractive index changes by photo excited carriers are a major mechanism responsible for LSFL. Furthermore, the appearance of random substructures as small as 30 nm superimposing low spatial frequency ripples is demonstrated and their possible origin is discussed. PMID- 20299730 TI - Nanofluidics in hollow nanowires. AB - We present a novel scheme for producing nanotube membranes using free-standing hollow nanowires, with easily controllable dimensions. GaAs-AlInP core-shell nanowires were grown by metal-organic vapor phase epitaxy and were partially embedded in a polymer film. The GaAs core and substrate were etched selectively, leaving tubes with open access to both sides of the membrane. Electrophoretic transport of T4-phage DNA through the hollow nanowires was demonstrated using epifluorescence microscopy. PMID- 20299731 TI - Black-box modeling to estimate tissue temperature during radiofrequency catheter cardiac ablation: Feasibility study on an agar phantom model. AB - The aim of this work was to study linear deterministic models to predict tissue temperature during radiofrequency cardiac ablation (RFCA) by measuring magnitudes such as electrode temperature, power and impedance between active and dispersive electrodes. The concept involves autoregressive models with exogenous input (ARX), which is a particular case of the autoregressive moving average model with exogenous input (ARMAX). The values of the mode parameters were determined from a least-squares fit of experimental data. The data were obtained from radiofrequency ablations conducted on agar models with different contact pressure conditions between electrode and agar (0 and 20 g) and different flow rates around the electrode (1, 1.5 and 2 L min(-1)). Half of all the ablations were chosen randomly to be used for identification (i.e. determination of model parameters) and the other half were used for model validation. The results suggest that (1) a linear model can be developed to predict tissue temperature at a depth of 4.5 mm during RF cardiac ablation by using the variables applied power, impedance and electrode temperature; (2) the best model provides a reasonably accurate estimate of tissue temperature with a 60% probability of achieving average errors better than 5 degrees C; (3) substantial errors (larger than 15 degrees C) were found only in 6.6% of cases and were associated with abnormal experiments (e.g. those involving the displacement of the ablation electrode) and (4) the impact of measuring impedance on the overall estimate is negligible (around 1 degrees C). PMID- 20299732 TI - Efficient computation of the elastography inverse problem by combining variational mesh adaption and a clustering technique. AB - This paper is concerned with an efficient implementation suitable for the elastography inverse problem. More precisely, the novel algorithm allows us to compute the unknown stiffness distribution in soft tissue by means of the measured displacement field by considerably reducing the numerical cost compared to previous approaches. This is realized by combining and further elaborating variational mesh adaption with a clustering technique similar to those known from digital image compression. Within the variational mesh adaption, the underlying finite element discretization is only locally refined if this leads to a considerable improvement of the numerical solution. Additionally, the numerical complexity is reduced by the aforementioned clustering technique, in which the parameters describing the stiffness of the respective soft tissue are sorted according to a predefined number of intervals. By doing so, the number of unknowns associated with the elastography inverse problem can be chosen explicitly. A positive side effect of this method is the reduction of artificial noise in the data (smoothing of the solution). The performance and the rate of convergence of the resulting numerical formulation are critically analyzed by numerical examples. PMID- 20299733 TI - Improving initial polyp candidate extraction for CT colonography. AB - Reducing the number of false positives (FPs) as much as possible is a challenging task for computer-aided detection (CAD) of colonic polyps. As part of a typical CAD pipeline, an accurate and robust process for segmenting initial polyp candidates (IPCs) will significantly benefit the successive FP reduction procedures, such as feature-based classification of false and true positives (TPs). In this study, we introduce an improved scheme for segmenting IPCs. It consists of two main components. One is geodesic distance-based merging, which merges suspicious patches (SPs) for IPCs. Based on the merged SPs, another component, called convex dilation, grows each SP beyond the inner surface of the colon wall to form a volume of interest (VOI) for that IPC, so that the inner border of the VOI beyond the colon inner surface could be segmented as convex, as expected. The IPC segmentation strategy was evaluated using a database of 50 patient studies, which include 100 scans at supine and prone positions with 84 polyps and masses sized from 6 to 35 mm. The presented IPC segmentation strategy (or VOI extraction method) demonstrated improvements, in terms of having no undesirably merged true polyp and providing more helpful mean and variance of the image intensities rooted from the extracted VOI for classification of the TPs and FPs, over two other VOI extraction methods (i.e. the conventional method of Nappi and Yoshida (2003 Med. Phys. 30 1592-601) and our previous method (Zhu et al 2009 Cancer Manag. Res. 1 1-13). At a by-polyp sensitivity of 0.90, these three methods generated the FP rate (number of FPs per scan) of 4.78 (new method), 6.37 (Nappi) and 7.01 (Zhu) respectively. PMID- 20299734 TI - LaBr(3):Ce and SiPMs for time-of-flight PET: achieving 100 ps coincidence resolving time. AB - The use of time-of-flight (TOF) information in positron emission tomography (PET) enables significant improvement in image noise properties and, therefore, lesion detection. Silicon photomultipliers (SiPMs) are solid-state photosensors that have several advantages over photomultiplier tubes (PMTs). SiPMs are small, essentially transparent to 511 keV gamma rays and insensitive to magnetic fields. This enables novel detector designs aimed at e.g. compactness, high resolution, depth-of-interaction (DOI) correction and MRI compatibility. The goal of the present work is to study the timing performance of SiPMs in combination with LaBr(3):Ce(5%), a relatively new scintillator with promising characteristics for TOF-PET. Measurements were performed with two, bare, 3 mm x 3 mm x 5 mm LaBr(3):Ce(5%) crystals, each coupled to a 3 mm x 3 mm SiPM. Using a (22)Na point source placed at various positions in between the two detectors, a coincidence resolving time (CRT) of approximately 100 ps FWHM for 511 keV annihilation photon pairs was achieved, corresponding to a TOF positioning resolution of approximately 15 mm FWHM. At the same time, pulse height spectra with well resolved full-energy peaks were obtained. To our knowledge this is the best CRT reported for SiPM-based scintillation detectors to date. It is concluded that SiPM-based scintillation detectors can provide timing resolutions at least as good as detectors based on PMTs. PMID- 20299735 TI - Fully automated intrinsic respiratory and cardiac gating for small animal CT. AB - A fully automated, intrinsic gating algorithm for small animal cone-beam CT is described and evaluated. A parameter representing the organ motion, derived from the raw projection images, is used for both cardiac and respiratory gating. The proposed algorithm makes it possible to reconstruct motion-corrected still images as well as to generate four-dimensional (4D) datasets representing the cardiac and pulmonary anatomy of free-breathing animals without the use of electrocardiogram (ECG) or respiratory sensors. Variation analysis of projections from several rotations is used to place a region of interest (ROI) on the diaphragm. The ROI is cranially extended to include the heart. The centre of mass (COM) variation within this ROI, the filtered frequency response and the local maxima are used to derive a binary motion-gating parameter for phase-sensitive gated reconstruction. This algorithm was implemented on a flat-panel-based cone beam CT scanner and evaluated using a moving phantom and animal scans (seven rats and eight mice). Volumes were determined using a semiautomatic segmentation. In all cases robust gating signals could be obtained. The maximum volume error in phantom studies was less than 6%. By utilizing extrinsic gating via externally placed cardiac and respiratory sensors, the functional parameters (e.g. cardiac ejection fraction) and image quality were equivalent to this current gold standard. This algorithm obviates the necessity of both gating hardware and user interaction. The simplicity of the proposed algorithm enables adoption in a wide range of small animal cone-beam CT scanners. PMID- 20299736 TI - Practical dietary calorie management, body weight control and energy expenditure of diabetic patients in short-term hospitalization. AB - AIM: We investigated how dietary management affected body weight (BW) reduction and energy expenditure in obese and normal-weight type 2 diabetic patients. METHODS: Type 2 diabetic patients who were hospitalized for diabetic control (93 men and 51 women) were checked for resting energy expenditure (REE). Subjects were divided into the two groups according to body mass index (BMI): obese (BMI > or = 25), and normal-weight (BMI <25). Following the recommendations by JDS, JAS and JASSO, ideal body weight was calculated as [IBW=height (m) x height (m) x 22 (kg/m(2))], and dietary calorie (kcal/day) was determined as 25 kcal/kg IBW. RESULTS: Dietary calorie intake during hospitalization was similar in both groups. REE was greater in obese than in normal-weight patients. The difference between the calorie intake and energy expenditure (Deltacalorie) was -222+/-26 kcal in obese patients and 69+/-27 kcal in normal-weight patients. Obese patients therefore had larger BW decreases than normal-weight patients (-171+/-12 vs. 92+/-11 g/day, p<0.005). In the obese group, a positive correlation was found between the change of BW and Deltacalorie. This correlation remained after adjusting for age, BMI, gender, and respiratory quotient. Serum lipid profiles were significantly improved in both groups. CONCLUSION: These diet instructions showed the appropriate calorie restriction depending on the BMI and induced reasonable BW reduction in both obese and normal-weight subjects. The dietary program recommended by JDS, JAS and JASSO is practically useful for BW control and for improving lipid metabolism in type 2 diabetic patients. PMID- 20299737 TI - Effects of a fish-based diet on the serum adiponectin concentration in young, non obese, healthy Japanese subjects. AB - AIM: Adiponectin has insulin-sensitizing, anti-atherogenic, and anti-inflammatory properties, and researchers have recently reported that omega-3 polyunsaturated fatty acid (PUFA) can increase the serum adiponectin concentration, suggesting that dietary factors, such as fish intake, may have an influence on the serum adiponectin concentration. In general, Japanese subjects consume twice as much fish as people in other countries. We hypothesized that incremental change in serum omega-3 PUFA levels by fish intake is an important regulator of serum adiponectin even in Japanese subjects. The aim of this study was to explore the relationship among fish consumption, serum omega-3 PUFA, such as eicosapentaenoic acid (EPA), levels, and serum adiponectin levels. METHOD: We recruited 17 healthy Japanese volunteers (seven men and 10 women) for an 8-week fish-diet intervention (omega-3 PUFA 3.0 g/day) without affecting total energy intake, and measured serum adiponectin concentration and fatty acid profiles. RESULTS: Fish-diet intervention significantly increased the serum adiponectin concentration in women (from 13.5+/-4.6 to 15.8+/-5.2 microg/mL, p <0.01) but not in men (from 8.7+/-2.8 to 8.7+/-2.5 microg/mL). Serum omega-3 PUFA increased more in female subjects than male subjects after the fish-diet intervention (57.3+/-86.6 vs 150.9+/-46.7 microg/mL, p=0.011), suggesting that changes in omega-3 PUFA concentration may explain the different response between sexes. CONCLUSION: A fish-based diet intervention increased the serum adiponectin concentration in young, non-obese, healthy Japanese female subjects. The increment in serum omega-3 PUFA may regulate the serum adiponectin concentration. PMID- 20299738 TI - Radiation therapy: state of the art and the future. AB - Technical innovation in radiation therapy (RT) such as stereotactic irradiation, intensity modulated RT, image-guided RT, and brachytherapy using remote controlled after-loading system have made it possible to deliver ideally distributed radiation dose to the target with great accuracy, while sparing the adjacent organs at risk. As a result, tumor control rate by RT improved markedly and became excellent alternative to surgery for asymptomatic or mildly symptomatic brain tumors, early stage lung cancer, and low-risk prostate cancer. In locally advanced stage of cancer, randomized controlled trials established the chemoradiation therapy as a standard treatment option for patients with head and neck cancer, lung cancer, esophageal cancer, and cervical cancer. RT is also a valuable treatment for palliation of local symptoms caused by cancer with consistently high response rates. Minimally invasive therapy has come to be emphasized its needs in the background of increased tendency of elderly patients with cancer, and advances in conformal dose delivery technique raise the RT at a more important position in cancer therapy. However, adequate number of RT profession is indispensable to utilize highly-sophisticated RT technology. Substantiality of an education system for radiation oncologist, RT technologist, and medical physicists is our current most important issue. PMID- 20299739 TI - Crucial role of renin-angiotensin system in the pathogenesis of atherosclerosis. AB - The renin-angiotensin system (RAS) has been demonstrated to play a critical role in the initiation and progression of atherosclerosis, thereby contributing to development of cardiovascular diseases. Angiotensin II (Ang II), a major substrate in RAS, stimulates atherosclerosis through various deleterious effects such as endothelial dysfunction, cellular proliferation and inflammation. Recently, local RAS in vasculature is reported to play an important role. Many of these atherogenic actions of Ang II are mediated by reactive oxygen species (ROS). Investigation of the role of ROS and inflammation induced by RAS may provide a clue to understanding the pathophysiology of atherosclerotic diseases, and may lead to a new therapeutic strategy. PMID- 20299740 TI - Mechanisms of matrix metalloproteinase-9 upregulation and tissue destruction in various organs in influenza A virus infection. AB - Severe influenza is characterized clinicopathologically by multiple organ failure, although the relationship amongst virus and host factors that influence this morbid outcome and the underlying mechanisms of action remain unclear. The present study identified marked upregulation of matrix metalloproteinase (MMP)-9 and pro-inflammatory cytokine tumor necrosis factor alpha (TNF-alpha) in various organs after intranasal infection of influenza A WSN virus. MMP-9 and TNF-alpha were upregulated in the lung, the site of initial infection, as well as in the brain and heart. The infection-induced MMP-9 upregulation was inhibited by anti TNF-alpha antibodies and by anti-oxidative reagents pyrrolidine dithiocarbamate and N-acetyl-L-cysteine, which inhibit activation of nuclear factor kappa B (NF kappaB), as well as by nordihydroguaiaretic acid, which inhibits activation of activator protein 1 (AP-1). In addition, MMP-9 upregulation via TNF-alpha was also suppressed by inhibitors of mitogen-activated protein kinases (MAPKs), such as extracellular signal-regulated kinase 1/2 and p38, and partly by a c-Jun N terminal kinase inhibitor. These results indicated that the influenza-induced MMP 9 upregulation in various organs is mediated through MAPK-NF-kappaB- and/or AP-1 dependent mechanisms. Strategies that neutralize TNF-alpha as well as inhibitors of MAPK-NF-kappa B- and/or AP-1-dependent pathways may be useful for suppressing the MMP-9 effect and thus preventing multiple organ failure in severe influenza. PMID- 20299741 TI - Function of the frontal lobe in autistic individuals: a proton magnetic resonance spectroscopic study. AB - PURPOSE: In this investigation, we studied differences in chemical metabolites in certain brain regions between autistic patients and normal control subjects. METHODS: Proton magnetic resonance spectroscopy ((1)H-MRS) was used to evaluate functional activity in these regions. Specific regions studied were right and left dorsolateral prefrontal cortex(DLPFC) and the anterior cingulated cortex(ACC). RESULTS: In the ACC, the N acetylaspartate(NAA)/creatine/phosphocreatine(Cr) ratio in autistic patients (n=31) was significantly lower than that in control subjects (n=28). The decrease in the NAA/Cr ratio for the ACC was much greater in the group with worst social ability. NAA/Cr for the left DLPFC and social ability of autistic patients also correlated well. Furthermore, NAA/Cr for the left DLPFC in the group with intelligence quotient (IQ) below 50 was significantly less than in controls. NAA/Cr for the right DLPFC in autistic patients was not decreased compared to controls, and did not correlate with IQ or social ability. CONCLUSIONS: These findings suggest neuronal dysfunction in the ACC and left DLPFC in autism, and also a relationship between social disability and metabolic dysfunction in these regions. Dysfunction in the ACC and the left DLPFC may contribute to the pathogenesis of autism. PMID- 20299742 TI - Nutritional status, feeding practice and incidence of infectious diseases among children aged 6 to 18 months in northern mountainous Vietnam. AB - OBJECTIVE: To assess the prevalence of undernutrition, incidence of infectious diseases and the situation of feeding practices to determine the risk factors for undernutrition among children aged 6 to 18 months in rural Vietnam. DESIGN: A cross-sectional study was conducted among one hundred eighty-eight mother-child pairs in Bac Giang, Vietnam. Weight and height of the children were measured and referred to data from the WHO/CDC/NCHS. Incidence of infectious diseases was diagnosed based on the WHO Recommended Surveillance Standards. Data on socio demographic variables and feeding practices were obtained through a structured questionnaire. RESULT: The prevalence of underweight, stunting and wasting was 19.7%, 23.4% and 5.3%, respectively. The incidence of diarrhea and acute respiratory infections (ARIs) during the last 14 days of the interview was 12.2% and 20.2%, respectively. Although 99% of the children were breastfed, the prevalence of exclusive breastfeeding in the first 4 mo was 21.3%. Non-exclusive breastfeeding in the first 4 month (OR 3.95, p=0.025) and low birth weight (OR 4.38, p=0.009) were associated with underweight in the children, while incidence of infectious disease was not (OR 1.16, p=0.734). CONCLUSION: Undernutrition is highly prevalent in the study site and non-exclusive breast feeding is one of the risk factors. PMID- 20299743 TI - Increasing early insulin secretion compensate adequately for hepatic insulin resistance in CCl4-induced cirrhosis rats. AB - A number of recent publications have reported an increased frequency prevalence of glucose intolerance with hyperinsulinemia in liver cirrhosis. The aim of this work was to detect, in CCl(4)-induced liver cirrhosis rat, the presence and starting point of muscle and liver insulin resistance. Eighteen rats received intraperitoneal injection of 2 ml of soybean oil containing of CCl(4) twice a week for 20 weeks. We executed standard oral glucose tolerance and clamp study to evaluate systemic insulin resistance. Hepatic glucose uptake was much lower in CCl(4) group than that in control group, but peripheral glucose uptake was not decreased in this study. In contrast, early-phase insulin secretion was enhanced in CCl(4) rat using oral glucose load during clamp methods. These data suggested that increased early insulin secretion compensate adequately for hepatic insulin resistance in rats. However there was a report that peripheral glucose uptake was decreased in the case of human liver cirrhosis, which was formed in the course of time. In a chronic condition, this may be associated with reduced insulin content and developed systemic insulin resistance in liver cirrhosis. Then a long term observation study will be required to examine the presence of muscle insulin resistance in liver cirrhosis. PMID- 20299744 TI - Prediction of Japanese children at risk for complications of childhood obesity: gender differences for intervention approaches. AB - Childhood obesity is one of the most serious public health problems in Japan, especially in Tokushima compared with other prefectures. This study was designed to clarify the life habits which predispose to development of obesity and can be modified through an appropriate intervention program to combat childhood obesity and its lifestyle-related diseases. A total of 216 school children from Itano Town, a municipality of Tokushima Prefecture, Japan, who are attending the fourth grade (9-10 years) of elementary schools, participated in the study from 2004 to 2007. The study included child's life habits questionnaire, investigating physical activity by recording the daily steps using a pedometer, anthropometric measurements, hematological examination and hemodynamometry in a cross-sectional survey during a two-month period from June to July every year. We conclude that there are considerable gender-related differences for developing obesity and other lifestyle-related diseases; and all intervention strategies against obesity must consider such gender differences. For example, restriction of television watching hours must be intervened for controlling obesity in boys, however for girls, promotion of exercise practice or making more steps per day with adequate sleeping periods should be intervened as the proper approaches for preventing and controlling obesity and other lifestyle-related diseases. PMID- 20299745 TI - Determinants of life satisfaction among Japanese elderly women attending health care and welfare service facilities. AB - Prolonged life expectancy must be recognized as an excellent achievement of modern medicine, but not all the elderly people are satisfied with their lives. Life satisfaction is a multi-dimensional issue that depends on many objective and subjective characteristics. In this study, we aimed at investigating the factors affecting life satisfaction of 314 elderly Japanese women attending in 28 elderly care and welfare facilities at Tokushima Prefecture, Japan. Our results indicated that elderly subjects with depression tendencies always show significantly lower degrees of life satisfaction than others who are not depressed (p<0.001) regardless of their cognitive status. Furthermore, elderly women who shared decision for their living place and whose opinions were considered for daily life decisions reported significantly more life satisfaction levels than others. We conclude that elderly life satisfaction is affected by various determinants however, with different influencing weight. Life satisfaction of elderly people, with or without dementia, is greatly affected by their mood status and share in decision making. Avoiding elderly people depressive mood, sharing them in various daily decisions, considering their opinions, and allowing them to decide their elderly-care facility placement are crucial determinants for their life satisfaction and essential for their coping, adaptation, well-being and successful aging. PMID- 20299746 TI - Relationship between Barthel Index scores during the acute phase of rehabilitation and subsequent ADL in stroke patients. AB - The Barthel Index (BI) cannot be used to measure initial stroke severity or by extension, to stratify patients by severity in acute stroke trials because most patients are bedbound in the first few hours after stroke, either by their deficit or by medical directive. Our objectives were to clarify the threshold of acute BI for use in the prediction of subsequent independence in activities of daily living (ADL) and to assist in the definition of acute stroke rehabilitation goals. Subjects comprised 78 patients out of 191 inpatients admitted with acute stroke at our hospital during 2006-2007. The BI ADL score was divided into 2 ranges (BI> or =60 and < or =40), in a process similar to previous studies. During the acute period (from onset to approximately 3 weeks), all patients with a BI> or =40 could improve their ADL in 6 months. Patients with a BI< or =40 exhibited two ADL recovery outcomes (improved and no change) at 6 months. We also found that the skill level of basic activities related to standing was significant indicator of BI improvement (P<0.001). BI scores determined at approximately 3 weeks were reliable predictors of ADL disabilities at 6 months. PMID- 20299747 TI - Different interaction between HIV-1 Vif and its cellular target proteins APOBEC3G/APOBEC3F. AB - We examined a series of site-directed point mutants of human immunodeficiency virus type 1 (HIV-1) Vif for their interaction with cellular anti-viral factors APOBEC3G/APOBEC3F. Mutant viruses that display growth-defect in H9 cells did not counteract effectively APOBEC3G and/or APOBEC3F without exception, as monitored by single-cycle infectivity assays. While growth-defective mutants of Vif C terminal region were unable to suppress APOBEC3G/APOBEC3F, some N-terminal region mutants did neutralize one of APOBEC3G/APOBEC3F. These data have suggested that members of APOBEC3 family other than APOBEC3G/APOBEC3F are not important for anti HIV-1 activity. Furthermore, APOPEC3G/APOBEC3F were found to differently associate with Vif in virions as analyzed by equilibrium density centrifugation. Taken together, these results indicated that interaction of HIV-1 Vif and APOBEC3G is distinct from that between Vif and APOBEC3F. PMID- 20299748 TI - Fibroblast growth factor 23 mediates the phosphaturic actions of cadmium. AB - Phosphaturia has been documented following cadmium (Cd) exposure in both humans and experimental animals. The fibroblast growth factor 23 (FGF23)/klotho axis serves as an essential phosphate homeostasis pathway in the bone-kidney axis. In the present study, we investigated the effects of Cd on phosphate (Pi) homeostasis in mice. Following Cd injection into WT mice, plasma FGF23 concentration was significantly increased. Urinary Pi excretion levels were significantly higher in Cd-injected WT mice than in control group. Plasma Pi concentration decreased only slightly compared with control group. No change was observed in plasma parathyroid hormone and 1,25-dihydroxy vitamin D(3) in both group of mice. We observed a decrease in phosphate transport activity and also decrease in expression of renal phosphate transporter SLC34A3 [NaPi-IIc/NPT2c], but not SLC34A1 [NaPi-IIa/NPT2a]. Furthermore, we examined the effect of Cd on Npt2c in Npt2a-knockout (KO) mice which expresses Npt2c as a major NaPi co transporter. Injecting Cd to Npt2aKO mice induced significant increase in plasma FGF23 concentration and urinary Pi excretion levels. Furthermore, we observed a decrease in phosphate transport activity and renal Npt2c expression in Cd injected Npt2a KO mice. The present study suggests that hypophosphatemia induced by Cd may be closely associated with the FGF23/klotho axis. PMID- 20299749 TI - Very low-frequency rTMS modulates SEPs over the contralateral hemisphere. AB - In order to investigate the transcallosal effects of repetitive transcranial magnetic stimulation (rTMS), we studied median somatosensory evoked potentials (SEPs) before and after applying monophasic very low-frequency (0.2 Hz) subthreshold rTMS over the right motor cortex. For SEPs, median nerve was stimulated on each side. Sham rTMS served as the control. Twelve healthy subjects participated in this study. After rTMS over the right hemisphere, the amplitude of N34 component in right median SEPs recorded from the left parietal scalp (C3') increased significantly. Other components of right or left median SEPs or those after sham stimulation showed no changes. Monophasic 0.2 Hz subthreshold rTMS over the motor cortex predominantly affected the contralateral SEPs, probably through the transcallosal pathway. PMID- 20299750 TI - Tracking overweight and obesity in Japanese children; a six years longitudinal study. AB - Childhood overweight/obesity is growing steeply, globally. It is usually regarded as a risk factor for severe obesity over life-time course. Here, we investigated temporal course of overweight/obesity development in Japanese school children. A six-year longitudinal study was performed on 16,245 Japanese primary school children (8,427 boys and 7,818 girls) comprising three cohorts of 1(st) approximately 3(rd) grade. A baseline survey was conducted at 2001, followed by annual baseline studies from 2002 approximately 2007 to determine the prevalence and track overweight/obesity. Our results showed that the prevalence of overweight was 15 approximately 23% in boys and 15 approximately 18% in girls, however, for obesity it ranged between 4 approximately 7% in boys; and 2 approximately 4% in girls. As regards for tracking status, 60 approximately 80% of overweight and 35 approximately 70% of obese Japanese primary school boys track into overweight or obese junior high school adolescents. However, these percentages are lower among primary school girls, where only 50 approximately 70% overweight and 30 approximately 60% obese primary school girls track into overweight and obese adolescents, respectively. We conclude that Japanese boys are fatter than girls; and approximately 80% of overweight/obese Japanese primary school children track into junior high school overweight/obese adolescents. PMID- 20299751 TI - Weight and height growth velocities of Japanese boys and girls between age 7 and 14 years: a critical window for early adolescent overweight risk. AB - Childhood overweight is an important worldwide problem of public health concern, with metabolic, physical and psychosocial complications. More and more evidence is accumulating that children who gain weight rapidly earlier in life are at higher risk of becoming overweight later in adulthood life. Therefore, in a seven year longitudinal study, we studied mid-childhood and early adolescence weight and height growth velocities among 5,024 Japanese 2(nd) grade primary school boys and girls along with its effect on the likelihood of being overweight adolescents by the age of 14 y. Our findings showed that weight growth velocity of both sexes was associated with being overweight at the end of longitudinal study. Boys' risk of accelerated weight growth velocity and becoming overweight adolescents was almost doubled during ages 7 approximately 11 y and become reduced afterward. Otherwise, odds ratios of girls' weight growth velocity peaks were found only at ages from 9 approximately 10 and 10 approximately 11 y. Thus, we suggest a critical window of mid-childhood period associated with adolescence risk of overweight, and we recommend that studying weight growth determinants during 7 approximately 11 y of boys and 9 approximately 11 y of girls may help in developing and applying proper programs for prevention and intervention of overweight problem. PMID- 20299752 TI - Radiographic comparison between male and female patients with lumbar spondylolysis. AB - We studied the lumbar spines of 117 adults (39 women and 78 men) with spondylolysis unrelated to low back pain using multidetector computed tomography (CT). Of the 117 subjects with spondylolysis, including five with multiple-level spondylolysis, there were 124 vertebrae with spondylolysis. In adult lumbar spines with unilateral spondylolysis, there was no significant difference between the incidence of spondylolisthesis in female and male subjects. However, in those with bilateral spondylolysis, there was a significantly higher incidence of spondylolisthesis in female subjects (90.9%) than in males (66.2%). Furthermore, females with bilateral spondylolysis had significant more slippage than males. Lumbar index and lumbar lordosis were not significantly different between male and female subjects, and did not significantly correlate with slippage. In conclusion, to treat acute spondylolysis in adolescents, it is important to obtain bony union at least unilaterally, especially in female subjects, to prevent further slippage. PMID- 20299753 TI - Immunohistochemical analyses of parathyroid hormone-dependent downregulation of renal type II Na-Pi cotransporters by cryobiopsy. AB - The "in vivo cryotechnique" (IVCT) is a new method of morphological analysis which has the advantage of freezing tissues in living animals without stopping their blood circulation. The purpose of this study was to investigate the effect of parathyroid hormone (PTH) on renal type II Na-Pi transporters (NaPi-IIa and NaPi-IIc) and "cryobiopsy" (CB) using special cryoforceps as a simple method of the IVCT. The kidney tissues were biopsied at various time points after PTH administration by CB using liquid nitrogen as the cryogen. By hematoxylin-eosin (HE) staining the kidney tissues, well-frozen areas without visible ice crystals were obtained in the tissue surface areas, and the brush border membrane (BBM) of proximal tubules was well preserved at a light microscopic level. Immunohistochemical evaluation showed that PTH downregulated NaPi-IIa and NaPi IIc at the BBM, being controlled by a different mechanism. In this method, the PTH-induced internalization of NaPi-IIc from microvilli to subapical compartments was not observed in the tissue preparations. NaPi-IIc protein appears to be degraded in microvilli of the proximal tubular cells after the injection of PTH. We suggest that CB using liquid nitrogen is useful to investigate renal type II Na-Pi transporters at the light microscopic level. PMID- 20299754 TI - Early ambulation after total knee arthroplasty prevents patients with osteoarthritis and rheumatoid arthritis from developing postoperative higher levels of D-dimer. AB - This study aimed to clarify the therapeutic effects of postoperative ambulation after total knee arthroplasty (TKA) on deep venous thrombosis (DVT) in patients with osteoarthritis (OA) and rheumatoid arthritis (RA) after TKA. Subjects of this study were thirty-seven inpatients (21 inpatients: OA, 16 inpatients: RA) undergoing TKA (32 female and 5 male). Subjects were divided into two groups, deep venous thrombosis (DVT) group (n=25) and non-DVT group (N group, n=12). The cutoff value was 10.0 microg/ml plasma D-dimer level measured on 7(th) postoperative day. The N group was below the cutoff value. Another cutoff value divided into two groups, ambulatory group (n=26) and non-ambulatory group (n=11). Ambulatory group was the date of ambulation beginning below 7(th) day. Statistical analysis confirmed that all subjects showed a significant correlation to the date of ambulation. Postoperative ambulation beginning had strong association with the level of D-dimer (r=0.71). Group comparison showed that the non-ambulatory group had significant higher values of D-dimer than ambulatory group (P=0.022). Typical case supported these results. Postoperative early ambulation within a week after TKA kept patients with OA and RA after TKA lower level of D-dimer. PMID- 20299755 TI - Clinical significance of Galectin-3 in clear cell renal cell carcinoma. AB - Overexpression of galectin-3 in a variety of cancer cell lines has been shown to correlate with tumor progression and metastasis. In this study, we investigated the expression of galectin-3 in clear cell renal cell carcinoma (CC-RCC) and evaluated the relationship between galectin-3 expression levels and the clinicopathological features of CC-RCC. Expression of galectin-3 in the kidney cancer cell lines Caki-1, Caki-2, A704, ACHN and KPK-1 were evaluated using western blot analysis, while galectin-3 expression in CC-RCC tissues and normal parenchyma were measured by real-time PCR and immunohistochemistry. We found that galectin-3 was overexpressed in the Caki-1, Caki-2, A704, ACHN and KPK-1 cell lines and that the expression level in CC-RCC was also significantly higher than that in renal parenchyma obtained from the same patient samples (p=0.039). Galectin-3 expression in CC-RCC with distant metastasis was also significantly higher than that in CC-RCC without distant metastasis (p=0.045). In conclusion, we revealed that galectin-3 is highly expressed in CC-RCC, especially in CC-RCC with distant metastasis, suggesting that galectin-3 may serve as a novel target molecule for predicting CC-RCC metastasis. PMID- 20299756 TI - A huge ovarian smooth muscle tumor: a case report. AB - Ovarian smooth muscle tumors are a very rare type of ovarian tumor. In this paper, we report the case of a 62-year-old woman who had a huge smooth muscle tumor of the right ovary. The values of all the serum tumor markers were within normal limit. The tumor measured 25 cm in diameter and weighed 6,200 g. Histological examination revealed that coagulative cellular atypia was moderate to severe, necrosis was not present and mitotic index was low. According to the criteria for the evaluation of the uterine smooth muscle tumors, this huge tumor was diagnosed as atypical leiomyoma. However, we finally made a diagnosis of this tumor as a smooth muscle tumor of uncertain malignant potential (STUMP) because of its huge size. Further information is required regarding the characteristics of ovarian smooth muscle tumor and the propriety to introduce uterine tumor histological criteria to ovarian tumors. PMID- 20299757 TI - Desensitization treatment with cisplatin after carboplatin hypersensitivity reaction in gynecologic cancer. AB - Platinum-based chemotherapy is the standard regimen for the treatment of gynecologic cancers; however, hypersensitivity reactions (HR) to platinum often lead to discontinuation of this effective treatment. Here we performed a desensitization protocol for platinum infusion in 3 patients who required platinum re-administration after developing HR. Two patients (Case 1 and 2) were treated with the desensitization protocol successfully without developing HR during the subsequent 3 courses. Case 3 tolerated desensitization well for 2 courses, but in the 3(rd) course, she developed severe HR immediately after the initiation of cisplatin infusion because the desensitization protocol was unintentionally omitted. These cases show the usefulness and effectiveness of the desensitization protocol for the continuation of platinum treatment in patients who have undergone an extended number of treatments. PMID- 20299758 TI - Effects of the whole-body cryotherapy on a total antioxidative status and activities of some antioxidative enzymes in blood of patients with multiple sclerosis-preliminary study. AB - OBJECTIVE: There is evidence that multiple sclerosis (MS) is not only characterized by immune mediated inflammatory reactions but also by neurodegenerative processes. Neutralization of oxidative stress and excitotoxicity, might represent a therapeutic approach to provide neuroprotection in MS. The purpose of this study was to compare changes in total antioxidative status and activities of chosen antioxidative enzymes, such as: SOD, CAT in erythrocytes of patients with MS before and after using WBCT with control group. MATERIALS AND METHODS: 32 patients with multiple sclerosis (ICD10-G35) and 20 healthy subjects were recruited for the study. The examined MS group (n=16) was treated with a series of 10 daily exposures in a cryogenic chamber (2-3 min, from -120 degrees C to -110 degrees C) and program of exercises. The control MS group (n=16) had only exercises. Plasma TAS as well as SOD and CAT activities in erythrocytes were measured. RESULTS: The level of TAS in MS patients was distinctly reduced compared to healthy subjects. After two weeks of WBCT treatment an increase of TAS in the whole examined group (p>0.01) were observed in relation to control MS group. There was not increase of CuZnSOD and CAT activities. CONCLUSION: Our results suggest positive antioxidant effects of WBCT as a short-term adjuvant treatment for patients suffered due to MS. PMID- 20299759 TI - Long-term recurrence-free survivor after laparoscopic removal of solitary adrenal metastasis from endometrial adenocarcinoma. AB - Solitary adrenal metastasis from endometrial adenocarcinoma is extremely rare. We report herein the case of a laparoscopically resected solitary adrenal metastasis originating from endometrial adenocarcinoma. The patient was a 55-year-old woman who had undergone total abdominal hysterectomy for stage IIIc endometrial carcinoma, followed by 7 courses of adjuvant chemotherapy comprising carboplatin and paclitaxel. However, the patient developed an isolated right adrenal metastasis 15 months postoperatively. The solitary adrenal metastasis (diameter, 5.7 cm) was removed laparoscopically. The patient has now been in good health without recurrence for 5 years and 7 months after laparoscopic surgery. To the best of our knowledge, this is the first case of solitary adrenal metastasis originating from endometrial adenocarcinoma that is controlled for the long term by successful laparoscopic resection. PMID- 20299760 TI - Distribution and identification of airborne fungi in railway stations in Tokyo, Japan. AB - OBJECTIVES: The current study was performed to (1) understand the distribution of airborne fungi culturable on dichloran-glycerol agar (DG18) media over a one-year monitoring period, (2) identify the types of airborne fungi collected, and (3) compare and contrast under- and above-ground spaces, in two railway stations in Tokyo, Japan. METHODS: Measurements of airborne fungi were taken at stations A and B located in Tokyo. Station A had under- and above-ground concourses and platforms whereas station B had spaces only above-ground. Airborne fungi at each measurement position were collected with an air sampler on DG18 media. After cultivation of the sample plates, the number of fungi colonies was counted on each agar plate. RESULTS: In station A, the underground platform was characterized as (1) having the highest humidity and (2) a high concentration of airborne fungi, with (3) a high proportion of non-sporulating fungi (NSF) and Aspergillus versicolor. There was a strong positive correlation between the concentrations of airborne particles and fungi in station A. Common aspects of the two stations were (1) that fungi were mostly detected in autumn, and (2) there was no correlation between the humidity and concentration of fungi throughout the year. CONCLUSIONS: The results of this study indicate that the distribution and composition of fungi differ depending on the structure of the station. PMID- 20299761 TI - Industry and injury related hospital contacts: a follow-up study of injuries among working men in Denmark. AB - OBJECTIVES: To estimate proportions of injuries that are attributable to the work environment (excess fractions) among economically active men and to identify industries associated with an elevated injury risk. METHODS: A follow-up study was conducted among all economically active men in Denmark aged 20-59 yr 1 January 1999 (N=1,315,772) for first hospital contacts in the period 1999-2003 due to injury in five body regions. Age standardised hospital treatment ratios (SHR) were calculated by industry and excess fractions were estimated. RESULTS: The excess fractions by body region attributable to the work environment were: 22% (95% CI 18-26%) for lower extremities, 29% (95% CI 24-34%) for head and neck, 31% (95% CI 25-37%) for thorax, 36% (95% CI 30-43%) for upper extremities, and 39% (CI: 32-46%) for back injuries. We identified eight industries associated with significantly elevated risks for injuries to each of the five body regions. These were: "road contractors", "bricklayer, joiner, and carpentry work", "finishing (construction work)", "transport of goods", "fire service and salvage corps", "stone-works, pottery, and glass industry", "cleaning, laundries, and dry cleaners", and "slaughterhouse industry". CONCLUSIONS: There are substantial industrial inequalities in injury rates among male workers in Denmark. The size of the inequalities differs between body regions. PMID- 20299762 TI - Comparative study of the effect of basal diet formulation, dietary fat and cholesterol levels on the development of aortic atherosclerotic lesions in B6.KOR Apoeshl mice. AB - To optimize the adequate atherogenic diet composition for nutritional atherosclerosis studies utilizing B6.KOR-Apoe(shl) mice, we investigated the effect of dietary cholesterol, AIN formula, and dietary fats on the development of atherosclerosis. Cholesterol supplementation (0.15-2%) for 12 weeks resulted in a dose-dependent increase in the development of atherosclerosis. Furthermore, there were no significant differences in the degree of atherosclerosis between B6.KOR-Apoe(shl) mice fed a modified-AIN-76 diet and those fed a modified-AIN-93M diet containing corn oil or soybean oil for 10 and 12 weeks. The present experiment indicates that the adequate dietary level of cholesterol was 0.15%, and that further studies are necessary to determine the optimal level of various types of dietary oils for nutritional atherosclerosis experiments in B6.KOR Apoe(shl) mice. PMID- 20299763 TI - Analysis of sterol and other components present in unsaponifiable matters of mahua, sal and mango kernel oil. AB - The amount and characterization of phytosterol and other minor components present in three Indian minor seed oils, mahua (Madhuca latifolia), sal (Shorea robusta) and mango kernel (Mangifera indica), have been done. Theses oils have shown commercial importance as cocoa-butter substitutes because of their high symmetrical triglycerides content. The conventional thin layer chromatography (TLC), gas chromatography (GC) & gas chromatography-mass spectroscopy (GC-MS) techniques were used to characterize the components and the high performance thin layer chromatography (HPTLC) technique was used to quantify the each group of components. The experimental data showed that the all the three oils are rich in sterol content and among all the sterols, beta-sitosterol occupies the highest amount. Sal oil contains appreciable amount of cardenolides, gitoxigenin. Tocopherol is present only in mahua oil and oleyl alcohol is present in mango kernel oil. Hydrocarbon, squalene, is present in all the three oils. The characterization of these minor components will help to detect the presence of the particular oil in specific formulations and to assess its stability as well as nutritional quality of the specific oil. PMID- 20299765 TI - Effects of bleach activator, sodium alkyl acyloxybenzene sulfonate, on house dust mites (Dermatophagoides farinae). AB - House dust mites (Dermatophagoides farinae) in bedding and clothes are a major allergen. However, house dust mites cannot be killed by general washing conditions under 50 degrees C. Therefore, low-temperature washing conditions must be improved to eliminate house dust mites. Sodium alkyl acyloxybenzene sulfonate (OBS) is a bleach activator that is used to intensify the bleaching effects of some laundry products. The purpose of this study was to evaluate the effect of OBS on the elimination of house dust mites in low-temperature washing conditions. D. farinae was soaked in solutions containing different types of OBS for various durations and at various temperatures. The miticidal effects of the various washing conditions were also evaluated for D. farinae. Then sodium lauroyloxybenzene sulfonate (OBS-12) produced the highest D. farinae mortality rate among the OBS solutions that were examined and had a stronger miticidal effect than available chlorine under general washing conditions. OBS exhibited miticidal effects under general washing conditions at low temperatures. Since OBS is already used as an additive in some laundry products to increase the bleaching activity, OBS can be easily used to kill house dust mites under general washing conditions. PMID- 20299764 TI - Antibacterial activity and the variation of Tanacetum parthenium (L.) Schultz Bip. essential oils from Turkey. AB - Water-distilled essential oils from herbal parts of Tanacetum parthenium from two different localities in Turkey were analyzed by GC and GC/MS. The essential oil of T. parthenium collected from Davutpasa-Istanbul location were characterized with camphor 49%, trans-chrysanthenyl acetate 22.1% and camphene 9.4%. Second plant sample is collected from the remote east end of the country Savsat-Ardahan location. The essential oil from this location was characterized with camphor 60.8% and camphene 6.8%. Unlike the former this sample contains trans chrysanthenyl acetate in trace amount and cis- chrysanthenyl acetate in very small amount (0.6%) which is not present in the first sample. Antibacterial activity of the oils were evaluated for five Gram (+) and five Gram (-) bacteria by using a broth microdilution assay. The highest activity was observed on Bacillus subtilis, Staphylococcus aureus and methicillin-resistant S.aureus however when compared with positive control oils showed higher MIC values. The oil of Istanbul-sample showed highest activity on B. subtilis (125 microg/mL) and methicillin-resistant S. aureus (125 microg/mL) which is two fold concentration when compared with the positive control chloramphenicol (62.5 microg/mL). The oil of Ardahan sample showed the highest activity on S. aureus (125 microg/mL) which is likewise two fold concentration of the positive control chloramphenicol (62.5 microg/mL). DPPH scavenging activity was 59.3% of the oil from Davutpasa at 15 mg/mL concentration. When compared to positive control alpha-tocopherol (94.6%) Savsat oil (28.2%) showed low and Davutpasa oil showed medium DPPH scavenging activity. All of the oils showed toxicity to Vibrio fischeri in the TLC bioluminescence assay. PMID- 20299766 TI - Novel synthesis of N-alkoxycarbonyl amino acids and surfactant properties of their sodium salts. AB - N-Acyl amino acids have been prepared from fatty acid chlorides and amino acids, but it may not be easy to vary the hydrophobic groups on the view point of availability. In this work, instead of acid halides, long alkyl chloroformates were prepared by the facile reaction of alcohols and triphosgene as an induction agent of hydrophobic group on amino acids. N-Alkoxycarbonyl amino acids were synthesized from alkyl chloroformate and amino acids under Schotten-Baumann reaction condition with some modification. Surfactant properties of their sodium salts were studied by surface tension measurements, dynamic light scattering and foaming test, and compared with those of N-acyl amino acids. Sodium salts of N alkoxycarbonyl amino acids showed an excellent surface tension lowering ability comparable to N-acyl amino acids, and they also exhibited good foaming ability and stability. PMID- 20299767 TI - Composition-insensitive highly viscous wormlike micellar solutions formed in anionic and cationic surfactant systems. AB - We investigated phase behavior and rheological properties of aqueous micellar phase formed in water/cocoyl glutamate neutralized with triethanol amine (CGT n)/hexadecyl trimethylammonium salt (CTAB or CTAC) systems, where n is a degree of neutralization. Micellar phase appears in wide composition range with respect to the surfactant mixing fraction in ternary phase diagrams at 25 degrees C. At high mixing fraction of cationic surfactant in the water/CGT-n/CTAB systems, one can observe a highly viscous micellar phase in which worm-like micelles are expected to form. Contrary to conventional systems in which worm-like micelles are formed, the zero-shear viscosity of the micellar solution in the water/CGT n/CTAB system with n=1.2 increases with the addition of cationic cosurfactant and once decreases after a maximum, then increases again and decreases after the second maximum. At n=1.5 and 2, highly viscous solution is observed in the relatively wide range of surfactant mixing fraction instead of two maxima of the viscosity curve observed at n=1.2. In the case of CTAC instead of CTAB we can observe narrow composition range for the maximum viscosity. Frequency sweep measurements were performed on the highly viscous samples in the water/CGT 1.5/CTAB system. Typical viscoelastic behavior of worm-like micellar solutions is observed; i.e. the curves of storage (G') and loss (G") moduli make a crossover and the data points of G' and G" can be fitted to the Maxwell model. Relaxation time against the mixing fraction of two surfactants behaves similarly to the zero shear viscosity change, whereas the plateau modulus continuously increases in the plateau region for the zero-shear viscosity curve. PMID- 20299768 TI - Three new cyclic diarylheptanoids and other phenolic compounds from the bark of Myrica rubra and their melanogenesis inhibitory and radical scavenging activities. AB - Ten cyclic diarylheptanoids (1-10), including three new compounds: myricanone 5-O alpha-L-arabinofuranosyl-(1-->6)-beta-D-glucopyranoside (7), myricanone 17-O-beta D-(6'-O-galloyl)-glucopyranoside (8), and 16-methoxy acerogenin B 9-O-beta-D apiofuranosyl-(1-->6)-beta-D-glucopyranoside (10), along with two flavonoids (11, 12), were isolated from the extracts of Myrica rubra (Myricaceae) bark. The structures of new compounds were determined on the basis of spectroscopic methods. On evaluation of compounds 1-12 against the melanogenesis in the B16 melanoma cells, six compounds, 3, 5, 7, 8, 10, and 12, exhibited inhibitory effects with 30-56% reduction of melanin content at 25 microg/mL with no or very weak toxicity to the cells (82-103% of cell viability at 25 microg/mL). In addition, upon evaluation of compounds 1-12 against the scavenging activities of free radicals [against the 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical], seven compounds, 1, 3, 5, 6, 8, 11, and 12, showed potent scavenging activity [IC(50) 2 21 microM (0.6-7.3 microg/mL)]. PMID- 20299769 TI - Formulation and in vitro evaluation of ketoprofen in palm oil esters nanoemulsion for topical delivery. AB - The aim of the present study is to formulate and investigate the potential of nanoemulsion formulation for topical delivery of ketoprofen. In this study, Palm Oil Esters (POEs) a newly introduced oil by Universiti Putra Malaysia researchers was chosen for the oil phase of the nanoemulsion, because the oil was reported to be a good vehicle for pharmaceutical use. Oil-in-water nanoemulsion was prepared by spontaneous emulsification method. The droplets size was studied by laser scattering spectroscopy (Nanophox) and Transmission Electron Microscopy (TEM). Franz diffusion cells were used, to determine the drug release and drug transferred through methyl acetate cellulose membrane (artificial membrane). The results of droplets size analysis shows the droplets are in the range of nanoemulsion which is below than 500 nm. The in vitro release profile shows a sufficient percentage of drugs released through the methyl acetate cellulose membrane. This initial study showed that the nanoemulsion formulated using POEs has great potential for topical delivery of ketoprofen. PMID- 20299770 TI - Principal component and interacting QTL analyses identify novel gene loci associated with metabolic traits in mice. AB - Previously analyzed F2 mice between KK/Ta and RR/Sgn strains were further investigated by defining appropriate permutation-derived threshold levels for significance and by searching pairwise gene interactions. In addition, a principal component analysis was conducted to extract a potential parameter that accounts for the joint occurrence of metabolic abnormalities. As a result, one significant interaction, containing novel QTL on chromosome 15, was identified for plasma total-cholesterol levels. For the principal component that potentially accounted for the joint occurrence of metabolic abnormalities, one significant QTL was identified on chromosome 12. This locus was not significant for any single trait. These complex genetic bases could not be disclosed as long as a separate trait was analyzed by traditional single QTL scans. PMID- 20299771 TI - Canine distemper virus infection in fennec fox (Vulpes zerda). AB - Fifteen 8-month-old fennec foxes imported from Sudan showed fever, mucopurulent ocular discharge, diarrhea, severe emaciation, seizures, and generalized ataxia, and died. Three of the 15 animals were presented for diagnostic investigation. Severe dehydration, brain congestion, and gastric ulcers were observed in all animals. In one animal, the lungs had failed to collapse and were multifocally dark red in appearance. Histopathologically, there were lymphohistiocytic meningoencephalitis with malacia, mild interstitial pneumonia, lymphoid depletion of lymphoid tissues and organs, and intestinal villous atrophy with intralesional coccidia. There were many intracytoplasmic and/or intranuclear inclusion bodies in the epithelial cells of the medullary velum, lungs, liver, kidneys, trachea, pancreas, stomach, gall bladder, urinary bladder, and ureters, and in macrophages of malacia foci and lymphocytes and macrophages of lymphoid organs. Additionally, intestinal coccidia were confirmed to be Isospora species by a fecal test. To our knowledge, this is the first report of canine distemper with intestinal coccidiosis in fennec fox. PMID- 20299772 TI - Participation in genetic testing research varies by social group. AB - BACKGROUND: Advances in technology have made individual access to personal genetic information foreseeable in the near future. Policy makers and the media forecast that the ready availability of personal genetic profiles would benefit both the individual and the health care system by improving outcomes and decreasing cost. However, there is a significant gap between having access to genetic data and either wanting or understanding the information it provides. OBJECTIVE: Our primary aim was to evaluate, using a population-based sample of healthy adults, whether gender, race and education status influences interest and participation in a multiplex genetic susceptibility test. METHODS: Healthy, insured individuals, 25-40 years of age, were approached via a large, integrated health system in which primary and specialty care is available. Study participants were offered personalized genetic risk information on 8 common chronic health conditions. Social groups historically known not to participate in genetic research (men, African Americans and those from lower education neighborhoods) were oversampled. We describe the recruitment outcomes and testing decisions of these social groups. RESULTS: We found that even among those with access to health care, African Americans were less likely to participate in the multiplex genetic susceptibility test, while those from higher education neighborhoods were more likely to participate. CONCLUSIONS: Our results suggest that large social groups will likely be underrepresented in research in personalized genomics even when robust population-based recruitment strategies are employed. PMID- 20299773 TI - First results of [11C]choline PET/CT-guided secondary lymph node surgery in patients with PSA failure and single lymph node recurrence after radical retropubic prostatectomy. AB - INTRODUCTION: [(11)C]choline PET/CT provides the opportunity to detect small lymph node metastases (LNM) (>5 mm) in prostate cancer (PCa) with exact topographic allocation. PSA development after resection of single LN recurrence detected via [(11)C]choline PET/CT without adjuvant therapy is not yet analyzed. We wanted to evaluate the potential of [(11)C]choline PET/CT in the diagnosis of single LN recurrence after radical prostatectomy (RPE) and whether secondary resection can result in PSA remission. METHODS: We investigated 6 patients with biochemical recurrence (PSA: median 2.04, range 0.67-4.51 ng/ml) after RPE. A single suspicious LN was detected on PET/CT without suspicion of local relapse or distant metastasis. The suspicious and nearby LN were open dissected (09/2004 02/2008). Histological and PET/CT findings were compared and the postoperative PSA development was examined. RESULTS: All metastasis-suspicious LN could be confirmed histologically. The additionally removed 10 LN were all correctly negative for cancer. Three patients showed a complete permanent PSA remission (<0.01 (n = 2), <0.03 ng/ml (n = 1)) without adjuvant therapy (follow-up: median 24, range 21-35 months). CONCLUSIONS: In this small selected collective [(11)C]choline PET/CT achieved reliable results. After resection of single LNM in all patients the oncologic criteria of a remission were fulfilled. Three of 6 patients had a complete PSA remission without adjuvant therapy. Whether cure or a positive influence on the course of disease can be achieved in individual patients has to be shown in further studies. PMID- 20299774 TI - Addition of lidocaine suppositories to periprostatic nerve block enhances pain control in prostate biopsies: a placebo-controlled randomized trial. AB - PURPOSE: The aim of this study was to evaluate the efficacy of a combined topical and local anesthesia consisting of a transrectal lidocaine suppository followed by periprostatic nerve block (PNB) in comparison to the combination of transrectally applied lidocaine gel followed by PNB and PNB alone as methods of reducing pain during transrectal prostate biopsy. PATIENTS AND METHODS: 100 patients were randomized to four groups and received either a placebo suppository or 10 ml of 2% lidocaine gel or a suppository containing 60 or 120 mg of lidocaine 1 h before biopsy. Additionally, every patient received a PNB using 5 ml 2% lidocaine. After performing an extensive transrectal ultrasound-guided biopsy, pain was evaluated using a visual pain scale. RESULTS: The mean pain score in the placebo group was 3.4, in the lidocaine gel group it was 3.7, and in the 60 or 120 mg lidocaine suppository groups it was 2.4 and 2.5, respectively. No patient showed vegetative symptoms like sweating or symptomatic hypotonia and no patient had severe pain. CONCLUSION: The addition of lidocaine suppositories to PNB as a form of combined anesthesia showed a significantly better pain reduction than the addition of lidocaine gel to PNB or PNB alone. PMID- 20299775 TI - The role of exenterative surgery and urinary diversion in persistent or locally recurrent gynecological malignancy: complications and survival. AB - OBJECTIVE: Treatment options in patients with persistent or locally recurrent cervical cancer are limited. The aim of this study was to determine the chance of cure and associated morbidity following pelvic exenteration. PATIENTS AND METHODS: Consecutive patients who underwent pelvic exenteration between January 1992 and December 2006 at the University Hospital of Bern or the Karlsruhe Medical Center were evaluated. Time to recurrence, type of exenteration and urinary diversion, pathological stage, postoperative complications and survival were assessed. RESULTS: Initial therapy prior to diagnosis of persistent or locally recurrent disease included radiation therapy in 51%. Anterior exenteration was performed in 37 (86%) and total exenteration in 6 (14%). Half of the women underwent additional procedures. A continent urinary diversion was constructed in 16 and an ileal conduit in 27 patients. Early postoperative complications were generally minor and only 2 patients required surgical intervention. Four intestinal fistulas were successfully treated conservatively. Late complications were mainly tumor-related. Complication rates associated with the urinary diversion were low and there was no difference in complications between continent and incontinent diversions. The overall disease-specific 5-year survival rate after exenteration was 36.5%. Survival correlated significantly with surgical margin status. CONCLUSION: In patients with persistent or locally recurrent gynecological malignancy of the pelvis, exenteration is a viable option with long-term survival in over one third of patients. Continent urinary diversion did not show higher complication rates than an ileal conduit and should be considered even in irradiated patients. This may be of greater significance in younger patients in whom an intact body image can play an important role in quality of life. PMID- 20299776 TI - Downsizing a tumor thrombus of advanced renal cell carcinoma with neoadjuvant systemic therapy and resulting histopathological effects. AB - BACKGROUND: We report a treatment option in surgical therapy of locally advanced renal cell carcinoma (RCC). METHOD: A 63-year-old patient with locally advanced RCC including an atrial thrombus underwent 2 cycles of neoadjuvant therapy (Sutent 50 mg daily for 4 weeks followed by 2 weeks off) and then tumor surgery. Primary surgical therapy had to be delayed because of suspected bronchial carcinoma and additional diagnostics. After neoadjuvant therapy to downsize the tumor thrombus and exclusion of any additional malignant tumors, operation was done via abdominal access; no sternotomy was necessary. RESULTS: Histopathological examinations of the primary tumor after tyrosine kinase inhibitor therapy were evaluated and compared to tumor biopsy material taken before therapy. CONCLUSION: Neoadjuvant therapy with Sutent may represent a favorable treatment option in cases of locally advanced clear-cell RCC with extended tumor thrombus. PMID- 20299777 TI - The proportion of free PSA and upgrading of biopsy Gleason score after radical prostatectomy. AB - INTRODUCTION: Upgrading of biopsy Gleason score (GS) after radical prostatectomy (RP) to GS >or=7 is common in patients with low-grade prostate cancer in biopsy. We evaluated whether a low proportion of free PSA (%fPSA) and total PSA (tPSA) predict significant upgrading after RP. PATIENTS AND METHODS: 122 patients with biopsy GS 5 or 6 prostate cancer and a tPSA <10 ng/ml who underwent RP in our academic center were included in the study. The utility of prebiopsy %fPSA and tPSA as predictors of significant upgrading was evaluated. RESULTS: Among patients undergoing RP, upgrading to GS >or=7 was found in 61 of 122 (50%) patients. A low %fPSA was a predictor of significant upgrading of tumors with biopsy GS 5 or 6 prostate cancer in patients with tPSA <10 ng/ml. CONCLUSIONS: Our results suggest that the selection of prostate cancer patients for active surveillance or re-biopsy may be improved by using %fPSA as a predictor of significant upgrading. PMID- 20299778 TI - Is perioperative intravesically applied antibiotic solution effective in the prophylaxis of urinary tract infections after renal transplantation? AB - OBJECTIVES: To evaluate the efficacy of intravesically applied amikacin for the prophylaxis of urinary tract infections (UTIs) occurring in the first 3 months after kidney transplantation. METHODS: In a prospective, randomized, controlled trial, 200 consecutive renal transplant recipients were randomly divided into two equal groups. The bladders of the first group, the amikacin group, were filled with saline solution containing amikacin (1 g in adults and 30 mg/kg in pediatric patients) whereas the bladders of the patients of the second group, the control group, were filled with saline solution. Patients were followed up for 3 months after transplantation with urine cultures to evaluate the prevalence of posttransplantation UTIs in both groups. RESULTS: The overall incidence of UTIs was found to be significantly lower in the amikacin group (25 vs. 49%; p = 0.0007). In addition, male patients, patients with end-stage renal disease due to glomerulonephritis, patients receiving renal transplantation for the first time, or those from the amikacin group receiving a living-related graft had a significantly lower incidence of UTIs than their counterparts in the control group (p < 0.05). UTIs were most frequently caused by Escherichia coli (28.9%). CONCLUSIONS: Perioperative bladder irrigation with amikacin solution significantly decreases the overall incidence of UTIs in the first 3 months after kidney transplantation. PMID- 20299779 TI - Transient visual loss triggered by scuba diving in a patient with a petrous epidermoid and combined thrombotic risk factors. AB - A 25-year-old woman who developed transient neurological abnormalities after scuba diving is reported. The subsequent day she experienced transient left-side monocular blindness. Arterial ocular occlusion in apparently healthy young women is unusual, and a search for the cause of this devastating vascular event is mandatory. Occlusion of the left branch retinal artery, total occlusion of the left internal carotid artery, and a petrous apex epidermoid were found, together with a shortened prothrombin time (INR: 0.73), a slightly elevated serum cholesterol level (6.1 mmol/l) and combined thrombophilia (elevated FVIIIC plus type 2 sticky platelet syndrome). This case underlines the complex mechanism of thromboembolic diseases, and the importance of the acquired trigger (in the present case scuba diving) in addition to the long-term anatomical and biochemical risk factors. PMID- 20299780 TI - Inducible nitric oxide synthase-activated mitochondrial apoptotic pathway in hypoxic and aged rat hearts. AB - BACKGROUND: Hypoxia and aging determine on mammalian cells a stress response which implies modified production of oxidants, reactive oxygen species or reactive nitrogen species at the mitochondrial level, interfering with cell signaling proteins and inducing mitochondrial damage, apoptosis occurrence and functional consequences. OBJECTIVE: Here we report the effects of hypoxia on the in vivo morphological and biochemical response of young and aged Wistar rat hearts. METHODS: Left ventricles were excised from each experimental point and processed. Investigations of vascular endothelial growth factor (VEGF) expression and apoptotic events, mitochondrial damage, were performed by light and electron microscopy, respectively; endothelial, inducible and neuronal NOS, PKCalpha, pPKCalpha, caspase-3 expression and Apaf-1/cytochrome c complex formation were assessed by Western blotting and co-immunoprecipitation analyses, respectively. RESULTS: Besides morphological modifications, which confirm mitochondrial suffering upon hypoxia exposure in both young and aged hearts, the role played by PKCalpha in controlling nitric oxide synthase (NOS) protein level was investigated. Downstream PKCalpha activation, a dramatic iNOS expression increase, concomitant to enhanced apoptotic cell percentage and Apaf-1/cytochrome c co-immunoprecipitation, is evident in the hypoxic young, suggesting iNOS mediated activation of the mitochondrial apoptotic pathway. CONCLUSIONS: Moreover, overexpression of iNOS and VEGF in the hypoxic young rat hearts suggests that an increased VEGF level may allow coordinated development of the lymphatic and blood vasculature, necessary for fluid homeostasis and to counteract oxidative stress. Thus the inhibition of such growth factor proposes new therapeutic possibilities for diseases associated to vascular function and for solid tumors which show pathological angiogenesis and lymphoangiogenesis. PMID- 20299781 TI - The first cytogenetic map of the tuatara, Sphenodon punctatus. AB - Tuatara, Sphenodon punctatus, is the last survivor of the distinctive reptilian order Rhynchocephalia and is a species of extraordinary zoological interest, yet only recently have genomic analyses been undertaken. The karyotype consists of 28 macrochromosomes and 8 microchromosomes. A Bacterial Artificial Chromosome (BAC) library constructed for this species has allowed the first characterization of the tuatara genome. Sequence analysis of 11 fully sequenced BAC clones (approximately 0.03% coverage) increased the estimate of genome wide GC composition to 47.8%, the highest reported for any vertebrate. Our physical mapping data demonstrate discrete accumulation of repetitive elements in large blocks on some chromosomes, particularly the microchromosomes. We suggest that the large size of the genome (5.0 pg/haploid) is due to the accumulation of repetitive sequences. The microchromosomes of tuatara are rich in repetitive sequences, and the observation of one animal that lacked a microchromosome pair suggests that at least this microchromosome is unnecessary for survival. We used BACs bearing orthologues of known genes to construct a low-coverage cytogenetic map containing 21 markers. We identified a region on chromosome 4 of tuatara that shares homology with 7 Mb of chicken chromosome 2, and therefore the orthologous region of the snake Z chromosome. We identified a region on tuatara chromosome 3 that is orthologous to the chicken Z, and a region on chromosome 9 orthologous to the mammalian X. Since the tuatara determines sex by temperature and has no sex chromosomes, this implies that different tuatara autosome regions are homologous with the sex chromosomes of mammals, birds and snakes. We have identified anchor BAC clones that can be used to reliably mark chromosomes 3-7, 10 and 13, some of which are difficult to distinguish based on morphology alone. Fluorescence in situ hybridization mapping of 18S rDNA confirms the presence of a single NOR located on the long arm of chromosome 7, as previously identified by silver staining. Further work to construct a dense physical map will lead to a better understanding of the dynamics of genome evolution and organization in this isolated species. PMID- 20299782 TI - Relationship between assays of glycemia in diabetic subjects with advanced chronic kidney disease. AB - BACKGROUND: Relative to hemoglobin A(1c) (HbA(1c)), glycated albumin (GA) more accurately reflects recent glycemic control in diabetic patients on hemodialysis and peritoneal dialysis. These assays have yet to be compared in patients with advanced chronic kidney disease (CKD). METHODS: HbA(1c) and GA were simultaneously measured in 303 diabetic subjects: 70 with CKD prior to dialysis (CKD-stage 4), 184 with CKD after transplantation (TXP-stage 3) and 49 non nephropathy controls. RESULTS: Mean estimated GFR was 76, 46 and 26 ml/min in controls, TXP-3 and CKD-4 cases, respectively. Mean (SD) HbA(1c) (%) and GA (%) concentrations were 7.30 (1.40) and 16.8 (4.9) in controls, 7.28 (1.66) and 21.5 (6.4) in CKD-4 cases, and 7.21 (1.62) and 21.2 (5.5) in TXP-3 cases, respectively. The GA:HbA(1c) ratio differed significantly between non-nephropathy controls and both groups of CKD patients (both p < 0.001), but not between CKD-4 and TXP-3 cases (p = 0.92). The glucose:HbA(1c) ratio was inversely associated with GFR in all 254 nephropathy cases (r = -0.13; p = 0.04), while glucose:GA did not vary significantly based upon GFR (r = -0.08; p = 0.24). CONCLUSIONS: The relationship between glycated albumin and HbA(1c) is influenced by the presence of reduced GFR in diabetic patients with CKD. The accuracy of the HbA(1c) assay in diabetic subjects with severe nephropathy requires further investigation, although HbA(1c) performs relatively well with milder CKD. PMID- 20299783 TI - Suppressor of cytokine signaling-1 ameliorates expression of MCP-1 in diabetic nephropathy. AB - BACKGROUND: Janus kinase (JAK)/signal transducers and activators of transcription (STAT) contribute to diabetic nephropathy. Suppressor of cytokine signaling-1 (SOCS-1) is one of the negative feedback regulators of JAK/STAT signaling. This study investigated the effect of SOCS-1 on the JAK/STAT pathway and MCP-1 expression in diabetic nephropathy. METHODS: Streptozotocin-induced diabetic mice received pEF-FLAG-I/mSOCS-1 plasmid or pEF-FLAG-I vector for 4 weeks and were compared with age-matched nondiabetic mice. Functional and pathologic markers, expression of monocyte chemoattractant protein-1 (MCP-1) and TGF-beta1 and phosphorylation of STAT1 and STAT3 were assessed. The effect of SOCS-1 on the expression of MCP-1 in mesangial cells under high glucose conditions was also examined. RESULTS: Urine albumin excretion and renal hypertrophy were alleviated in diabetic mice by overexpression of SOCS-1. The expression of TGF-beta1 and MCP 1 and the activation of STAT1 and STAT3 were significantly inhibited in diabetic kidney by gene delivery of SOCS-1. In cultured mesangial cells, overexpression of SOCS-1 markedly suppressed high glucose-induced MCP-1 expression. CONCLUSIONS: This study suggests that SOCS-1 may attenuate renal damage by ameliorating MCP-1 expression and regulation of the phosphorylation of JAK/STAT in diabetic mice. PMID- 20299784 TI - Role of body composition in the glycaemic response to foods fed to three different ethnic groups: a pilot study. AB - AIM: To examine the role of overweight and obesity on the glycaemic response to foods across the whole population. DESIGN: Randomised, repeated measures design. SETTING: Oxford, UK. SUBJECTS AND METHODS: Twenty-seven healthy volunteers, 9 Caucasian, 9 Asian, and 9 African, voluntarily participated in the study. The glycaemic response to two breakfast cereals and two bread types was determined in obese and overweight subjects. RESULTS: The current study shows that a very strong correlation exists between fasting blood glucose, peak change in glucose and the IAUC for glucose with each of BMI and WC (r = 0.88, 0.92; 0.82, 0.82; 0.91, 0.81; p = 0.01, respectively) for the Caucasian group. In addition, there was a strong significant negative association between the mean GI values of the four foods and the BMI for the Caucasian subjects (r = 0.61, p < 0.05). Furthermore, there was a strong positive significant association between the mean GI values of the four foods and the percentage body fat mass for the Asian subjects (r = 0.67, p < 0.05). CONCLUSIONS: This study has shown that the GI values of foods are affected by body composition in Asian and Caucasian subjects. PMID- 20299785 TI - Preliminary evidence of a high risk of bleeding on aspirin plus clopidogrel in aspirin-naive patients in the acute phase after TIA or minor ischaemic stroke. AB - BACKGROUND: Aspirin plus clopidogrel (A+C) may be more effective than aspirin only (AO) acutely after TIA and minor stroke, but the risk of bleeding in the acute phase is uncertain. We determined this risk, focusing particularly on aspirin-naive patients. METHODS: We studied consecutive referrals to the EXPRESS study clinic from 1/4/02 to 31/3/08. A 30- to 90-day course of A+C was given to patients presenting acutely. Bleeding events were identified by face-to-face follow-up, diagnostic coding, and blood transfusion data. Unpublished data from the FASTER pilot trial were also studied. RESULTS: Among 633 EXPRESS patients treated with aspirin (+/- clopidogrel), there were 12 spontaneous bleeds (6 minor, 6 major/life-threatening) within 90 days after assessment, with a higher risk for A+C vs. AO (8/247 vs. 4/386, p = 0.047 overall; 5/247 vs. 1/386, p = 0.03 for major/life-threatening bleeds). The excess of major/life-threatening bleeds on A+C vs. AO was seen in aspirin-naive patients, (4/137 vs. 0/273, p = 0.01), but not in prior-aspirin patients (1/110 vs. 1/113, p = 0.98). All symptomatic bleeds in the FASTER pilot also occurred in aspirin-naive patients randomized to A+C (6/104 vs. 0/94, p = 0.03). In a pooled analysis, major/life threatening bleeding on A+C occurred in 9/241 aspirin-naive patients (90-day risk = 4.8%, 1.6-8.0) versus 1/204 prior-aspirin patients (p = 0.009). CONCLUSION: Although based on relatively few outcomes, the high risk of major bleeding on A+C acutely after TIA or minor stroke in aspirin-naive patients is a cause for concern. The potential risk to patients is sufficient to mandate detailed monitoring of bleeding risk in ongoing trials and stratify results by whether patients were aspirin-naive. PMID- 20299786 TI - Fibro-fatty volume of culprit lesions in Virtual Histology intravascular ultrasound is associated with the amount of debris during carotid artery stenting. AB - OBJECTIVES: This study aimed to evaluate the relationship between the amount of aspirated debris during distal balloon-protected carotid artery stenting (CAS) and the pre-intervention plaque composition, as assessed by Virtual Histology (VH) intravascular ultrasound (IVUS). METHODS: The study subjects were 25 consecutive patients (mean age, 73.0 +/- 5.2 years; 20 males and 5 females) who underwent CAS under distal balloon protection. The average rate of carotid stenosis was 74.6 +/- 12.9% by North American Symptomatic Carotid Endarterectomy Trial criteria. We assessed culprit plaque components by VH-IVUS before CAS. Aspirated debris was filtered, stained with HE and mounted onto glass slides. The quantity of debris was evaluated by measuring its surface area. We evaluated the relationship between the quantity of aspirated debris and VH-IVUS measurements before CAS. RESULTS: The amount of debris during CAS was positively correlated with the total plaque volume in grayscale IVUS (Rs = 0.480, p = 0.015) and fibro fatty volumes over the entire lesion length in VH-IVUS (Rs = 0.561, p = 0.001). CONCLUSIONS: Culprit lesions with large plaque volumes, especially larger fibro fatty volumes, as imaged by VH-IVUS, are associated with large amounts of debris during balloon-protected CAS. PMID- 20299787 TI - Impact of prestroke oral anticoagulation on severity and outcome of ischemic and hemorrhagic stroke in patients with atrial fibrillation. AB - BACKGROUND: Stroke prevention with oral anticoagulation is effective in patients with atrial fibrillation. An additional beneficial effect of oral anticoagulation prior to the event on stroke severity and prognosis was suggested in ischemic strokes. We tested whether this benefit is preserved after inclusion of hemorrhagic strokes and adjustment for prestroke living conditions. METHODS: Data were used from a prospective hospital-based intervention trial evaluating quality of care and outcome in ten district hospitals. All ischemic and hemorrhagic stroke patients with atrial fibrillation were included. We analyzed separate multivariable regression models to identify factors associated with prescription of oral anticoagulation before stroke and to investigate the independent effect of anticoagulation on admission stroke severity, 3-month mortality and functional outcome. RESULTS: The analysis comprised 804 (718 ischemic, 86 hemorrhagic) stroke patients admitted between July 2003 and March 2005. Males, patients aged 65-84, living independently, with diabetes, previous cerebrovascular event or additional high cardioembolic risks were more likely to receive oral anticoagulation before admission. Admission international normalized ratio (INR) between 2 and 3 (OR 0.35, 95% CI: 0.17-0.71) or higher (OR 0.32, 95% CI: 0.11 0.92) was associated with less severe strokes (including hemorrhagic strokes) compared with INR <2. Anticoagulation was associated with decreased risk of death and poor functional outcome (modified Rankin Scale >3) at 3 months (OR 0.54, 95% CI: 0.36-0.84, and OR 0.70, 95% CI: 0.47-1.06). After adjustment for stroke severity, anticoagulation had no additional effect on mortality and functional outcome. CONCLUSIONS: The beneficial effect of prestroke anticoagulation on stroke outcome related to the reduced stroke severity is not offset by adverse effects in hemorrhagic stokes. PMID- 20299788 TI - Mean platelet volume in the early phase of acute ischemic stroke is not associated with severity or functional outcome. AB - BACKGROUND: Previous studies reported an increase of mean platelet volume (MPV) in patients with acute ischemic stroke. However, its correlation with stroke severity has not been investigated. Moreover, studies on the association of MPV with functional outcome yielded inconsistent results. METHODS: We included all consecutive ischemic stroke patients admitted to CHUV (Centre Hospitalier Universitaire Vaudois) Neurology Service within 24 h after stroke onset who had MPV measured on admission. The association of MPV with stroke severity (NIHSS score at admission and at 24 h) and outcome (Rankin Scale score at 3 and 12 months) was analyzed in univariate analysis. The chi(2) test was performed to compare the frequency of minor strokes (NIHSS score < or =4) and good functional outcome (Rankin Scale score < or =2) across MPV quartiles. The ANOVA test was used to compare MPV between stroke subtypes according to the TOAST classification. Student's two-tailed unpaired t test was performed to compare MPV between lacunar and nonlacunar strokes. MPV was generated at admission by the Sysmex XE-2100 automated cell counter (Sysmex Corporation, Kobe, Japan) from EDTA blood samples. RESULTS: There was no significant difference in the frequency of minor strokes (p = 0.46) and good functional outcome (p = 0.06) across MPV quartiles. MPV was not associated with stroke severity or outcome in univariate analysis. There was no significant difference in MPV between stroke subtypes according to the TOAST classification (p = 0.173) or between lacunar and nonlacunar strokes (10.50 +/- 0.91 vs. 10.40 +/- 0.81 fl, p = 0.322). CONCLUSIONS: MPV, assessed within 24 h after ischemic stroke onset, is not associated with stroke severity or functional outcome. PMID- 20299789 TI - Difference in infarct volume and patterns between cardioembolism and internal carotid artery disease: focus on the degree of cardioembolic risk and carotid stenosis. AB - BACKGROUND AND OBJECTIVE: Infarct volume and patterns may vary according to the stroke subtype. Within each stroke subtype, however, it is not clear if the infarct volume and patterns are affected by the risk of cardioembolism (CE) and the degree of arterial stenosis. PATIENTS AND METHODS: We included consecutive patients with acute symptomatic ischemic lesions on diffusion-weighted imaging (DWI) performed within 48 h of symptom onset who had CE or internal carotid artery disease (ICAD). CE was divided into high-risk and medium-risk groups, and ICAD was divided into ICA occlusion (ICAO) and ICA stenosis (ICAS > or =50%) groups. DWI lesion patterns were classified as single versus multiple, and as large territorial versus perforating artery (large > or =2 cm, small <2 cm) versus pial artery versus border zone infarct. Infarct volumes and National Institutes of Health Stroke Scale (NIHSS) scores were obtained. RESULTS: Of the 167 patients included, 120 had CE (98 high-risk, 22 medium-risk) and 47 had ICAD (25 ICAO, 22 ICAS). The infarct volume was largest in the high-risk CE group, followed by the ICAO group. The infarct volumes in the medium-risk CE and ICAS groups were similar. Infarct volumes correlated with NIHSS scores. Single and large territorial infarcts were more common in the high-risk CE group, while multiple lesions as well as pial and border zone infarcts were more frequent in the ICAD subgroups. The lesion patterns of the medium-risk CE and ICAD groups were relatively similar. CONCLUSIONS: CE and ICAD have heterogeneous radiologic characteristics depending on the risk of embolism and the degree of carotid stenosis. PMID- 20299791 TI - Metabolic syndrome relates to lacunar stroke without white matter lesions: a study in first-ever lacunar stroke patients. AB - BACKGROUND: Metabolic syndrome (MetS) is a cluster of three or more of the following risk factors: obesity, elevated blood pressure, elevated triglyceride level, elevated glucose level, and low high-density lipoprotein level. Lacunar infarcts (LS) account for 25% of all ischemic strokes and are small, deeply located brain infarcts. Two different subtypes exist, which are distinguished by the presence of concomitant white matter lesions (WML) on brain imaging. We determined the prevalence of MetS in LS and the association between MetS with LS subtypes in a series of first-ever LS patients. METHODS: We included 92 patients with a first-ever LS, and 92 patients with a first-ever atheroslerotic cortical stroke (CS) matched for age and sex. LS subtypes were defined according to presence of concomitant WML. We defined MetS retrospectively according to previously defined standards. RESULTS: 35.9% of LS patients and 45.7% of CS patients had MetS (OR 0.67; 95% CI 0.37-1.20). MetS was more prevalent in LS without WML than in LS with WML (44.4 and 23.7%, respectively; OR 2.98; 95% CI 1.04-8.47). Similarly, MetS related more to CS compared to LS with WML (OR 2.56; 95% CI 1.03-6.37). CONCLUSION: MetS relates more strongly to LS without WML and to CS, than to LS with WML. Our results suggest a different underlying mechanism between LS without WML and CS, and lacunar stroke with WML. PMID- 20299792 TI - Stroke and action slowing: mechanisms, determinants and prognosis value. AB - AIM: The present study aimed to determine the mechanisms and determinants of stroke-related action slowing. METHODS: Thirty-six stroke patients not presenting any clinical motor deficit of the preferred hand (mean post-stroke delay 11 months) were compared to matched controls on Finger Tapping test (motor speed), Visual Inspection Time test (visual perceptual speed) and Simple and Choice Reaction Time tests. RESULTS: Patients were slower on all tests except Choice Reaction Time: Visual Inspection (p = 0.003), Finger Tapping test (p = 0.001), Simple Reaction Time (p = 0.002) tests were impaired including performance measured with the ipsi-lesional hand. This pattern and the uniform lengthening across the entire reaction time distribution both suggest that psychomotor slowing was due to slowing of perceptual and motor processes. The main determinant of action slowing was lesion location: (1) Visual Inspection Time = right inferior parietal lobulus (OR 18, 95% CI 2.9-108); (2) Finger Tapping = left frontal middle gyrus (OR 18, 95% CI 2.9-108) and lenticular nucleus (OR 59, 95% CI 1.9-1,775), and (3) Simple Reaction Time = right lenticular nucleus (OR 110, 95% CI 8-1,490) and posterior fossa (OR 55, 95% CI 3.4-890). Finally poor outcome depended on Tapping Frequency measured with the contra-lesional index (OR 0.1, 95% CI 0.02-0.5; p = 0.0005) and impairment on the Token test (OR 151, 95% CI 2.24-1136; p = 0.02). CONCLUSIONS: This study shows that stroke-related action slowing is mainly due to slowing of perceptual and motor processes. Action slowing was related to lesions of the large network. Finally Tapping Frequency is an independent predictor of outcome. This supports that action slowing is an important consequence of stroke and that it is a promising prognosis index. PMID- 20299790 TI - Novel hemostatic factor levels and risk of ischemic stroke: the Atherosclerosis Risk in Communities (ARIC) Study. AB - BACKGROUND AND OBJECTIVE: The role of hemostatic factor levels in cerebral infarction remains uncertain. We studied the association of levels of several under-studied hemostatic factors with ischemic stroke in a population-based cohort. METHODS: The Atherosclerosis Risk in Communities (ARIC) study includes 15,792 individuals aged 45-54 years at intake. Hemostatic factors II, V, IX, X, XI, XII, plasminogen and alpha(2)-antiplasmin were measured on frozen citrate plasma samples from 1990 to 1992. A case-cohort design was used, including all incident ischemic strokes (n = 89) over a median of 7.5 years and a stratified cohort random sample (n = 412). To determine the association of hemostatic factors with incident ischemic stroke, we computed hazard ratios (HRs) using multivariate proportional hazard regression analyses adjusted for demographic and other cardiovascular risk factors. RESULTS: The cohort random sample had a mean age (SD) of 56.9 (5.4) years and 42% were men. The age-, sex- and race-adjusted HRs for highest versus lowest quartiles were: factor XI (2.74, 95% CI 1.42-5.29), factor IX (1.92, 95% CI 0.99-3.73), and alpha(2)-antiplasmin (2.24, 95% CI 1.16 4.33). Correspondingly, the HRs of ischemic stroke per SD increment of factors XI, IX, and alpha(2)-antiplasmin were 1.64, 1.46 and 1.52, respectively (all p < 0.05). After multivariate adjustment including other clinical variables, the standardized HR remained significant for factor XI (1.50, 95% CI 1.10-2.05), but no other factor. CONCLUSION: A greater level of factor XI was associated with an increased risk of ischemic stroke. Higher factor XI levels might help identify patients at elevated ischemic stroke risk. PMID- 20299793 TI - Prominent chemopreventive and chemoenhancing effects for resveratrol: unraveling molecular targets and the role of C-reactive protein. AB - BACKGROUND: Resveratrol (RSVL) claims health benefits that pertain to the consumption of red wine/grapes. We currently evaluated the chemopreventive effects of RSVL, as well as its possible chemoenhancing effects when given with cisplatin (CP), in the Ehrlich ascites carcinoma (EAC) solid tumor model. Further, we monitored concomitant changes in serum levels of C-reactive protein (CRP), tumor necrosis factor-alpha (TNF-alpha), leukocytic count (LC) and lipid peroxidation (measured as malondialdehyde, MDA). RESULTS: EAC-bearing mice exhibited a markedly elevated LC (2 fold), CRP (11 fold) and MDA levels (2.7 fold). RSVL (20 or 40 mg/kg) elicited significant, dose-dependent reductions in tumor size (58 and 78%, respectively), as well as in LC (normalized), CRP (down to 2 fold), TNF-alpha (down to near control levels) and MDA levels (normalized). The chemopreventive effects for CP (55% reduction in cell growth) was significantly lower than that of RSVL (40 mg/kg, 79% inhibition). Interestingly, coadministration of RSVL (20 mg/kg) markedly enhanced the chemoprevention of CP. Correlation studies revealed a high degree of positive association between tumor growth and CRP (r = 0.89) and leukocytosis (r = 0.86), thus attesting to a diagnostic/prognostic role for CRP in this solid tumor. CONCLUSION: RSVL elicited remarkable cytotoxicity on its own and appreciably augmented those of CP as well. The extent of tumor progression in various mouse groups was highly reflected by CRP levels. RSVL acts prominently by reducing inflammatory cytokines, leukocytosis and oxidative stress. PMID- 20299794 TI - Carnitine deficiency aggravates cyclophosphamide-induced cardiotoxicity in rats. AB - BACKGROUND: This study examined, for the first time, the involvement of carnitine deficiency in cardiotoxicity, particularly cyclophosphamide (CP)-induced cardiomyopathy, as well as effects of carnitine supplementation with propionyl-L carnitine (PLC) on cardiotoxicity. METHODS: An animal model of carnitine deficiency was developed in rats treated with D-carnitine (DC)-mildronate (MD). Adult male Wistar albino rats were assigned to one of six treatment groups: the first three groups were injected intraperitoneally with normal saline, PLC (250 mg/kg/day), and DC (250 mg/kg/day) combined with MD (200 mg/kg/day), respectively, for 10 successive days. In groups 4-6, the same doses of normal saline, PLC and DC-MD were injected, respectively, during the 5 successive days before and after a single dose of CP (200 mg/kg). On day 6 after CP treatment, 24 hour urine was collected, then animals were sacrificed, and serum as well as hearts were isolated. RESULTS: CP caused a significant increase in serum creatine phosphokinase isoenzyme (CK-MB), lactate dehydrogenase (LDH), urinary carnitine excretion and clearance and intramitochondrial acetyl-CoA/CoA-SH, and a significant decrease in serum free carnitine, total carnitine and adenosine triphosphate (ATP) contents in cardiac tissue. In the carnitine-depleted rats, CP induced dramatic increases in CK-MB and LDH levels, carnitine clearance and intramitochondrial acetyl-CoA/CoA-SH, as well as progressive reduction in total carnitine and ATP in cardiac tissues. Interestingly, PLC supplementation completely reversed the biochemical and histopathological changes induced by CP to the control values. CONCLUSION: (1) Carnitine deficiency is a risk factor which is involved in CP-related cardiomyopathy; (2) serum and urinary carnitine levels should be monitored and viewed as indices of CP-induced multiple organ toxicity, and (3) carnitine supplementation, using PLC, prevents the development of CP-induced cardiotoxicity. PMID- 20299795 TI - Pentoxifylline inhibits integrin-mediated adherence of 12(S)-HETE and TNFalpha activated B16F10 cells to fibronectin and endothelial cells. AB - BACKGROUND: Pentoxifylline (PTX), a phosphodiesterase inhibitor, inhibits homing of metastatic B16F10 melanoma cells to the lung. Studies on the mechanism of action of PTX showed inhibition of adhesion of cultured melanoma cells to various extracellular matrix substrates and inhibition of cell surface integrin expression. The aim of this study was to determine the effect of PTX on surface expression of integrin and integrin-mediated adhesion induced by biological mediators, tumour necrosis factor (TNF) alpha and 12(S)-hydroxyeicosatetraenoic acid (HETE), in B16F10 cells. MATERIALS AND METHODS: B16F10 cells were treated with 12(S)-HETE (1 microM, 1 h), TNFalpha (5 ng/ml, 2 h) and phorbol 12-myristate 13-acetate (400 nM, 20 min), and the effect of PTX on these treatments was studied by flow cytometry, adhesion assay and confocal microscopy. RESULTS: 12(S) HETE and TNFalpha brought about an increase in the surface expression of beta(1) integrins and F10 cell adhesion to fibronectin and endothelial cells; this increased adhesion was mediated at least in part by alterations in the localization of beta(1) integrins. Pretreatment with PTX was able to completely abrogate this induction in integrin expression. CONCLUSION: PTX can inhibit surface expression of integrin and integrin-mediated adhesion induced by several biological mediators, and this might be a possible mechanism for its antimetastatic action, in vivo. PMID- 20299796 TI - Born to be bradycardic? PMID- 20299797 TI - Atypical ST segment elevation and ventricular fibrillation without structural heart disease: a new electrocardiographic presentation of a channelopathy? AB - Primary electrical syndromes are a group of rare inherited diseases that predispose to arrhythmias in the absence of structural abnormalities of the heart, and are associated with several ion channel mutations. Extrinsic factors, such as fever, may contribute to the development of electrical instability in these patients. We report the case of a 52-year-old patient who was admitted for syncope and had an in-hospital episode of ventricular fibrillation, who presented with an admission ECG showing marked precordial ST segment elevation (maximum 5 mm in V2). The patient did not have structural heart disease and during the hospital stay there was progressive ST segment normalization, with features suggestive of Brugada pattern. An automated defibrillator was implanted for secondary prevention of sudden cardiac arrest. We believe that these findings may represent a new form of presentation of a genetic electrical syndrome. PMID- 20299798 TI - Functional rs20417 SNP (-765G>C) of cyclooxygenase-2 gene does not predict the risk of recurrence of ischemic events in coronary patients: results of a 7-year prospective study. AB - OBJECTIVES: The -765G>C variation (rs20417 SNP) in the promoter of cyclooxygenase 2 (COX-2) gene has been demonstrated to lower COX-2 enzyme activity in the vasculature, thus affecting atherosclerotic plaque growth and stability. Therefore, this genetic variant may be a candidate influencing the residual risk. METHODS: In 285 coronary patients the incidence of major adverse cardiovascular events (MACEs), defined as a composite of cardiovascular deaths, non-fatal myocardial infarction and stroke, unstable angina and revascularization procedures, was monitored for a median of 7.8 years. The genotypes were obtained in 231 patients (81%) by PCR amplification and FAU I digestion. RESULTS: 89 MACEs (38.5%) were recorded during the follow-up in genotyped patients. Their incidence was not different in patients with GC or CC when compared with those with GG genotype (46.2 vs. 35.5% respectively; p = 0.14). Kaplan-Meyer analysis did not demonstrate any influence of COX-2 genotypes on the event-free survival time (log rank p = 0.55). After controlling for confounders, the -765G>C carrier status was not associated with significant variation in the risk of MACE or its individual components. CONCLUSIONS: These results suggest that the functional G-765C variant in the COX-2 gene is not a significant predictor of the recurrence of ischemic events in coronary patients. PMID- 20299799 TI - Cerebellum and source memory. AB - We report the case of a 40-year-old right-handed German-speaking man who presented with ischemic stroke in the territories of the right superior cerebellar artery and posterior inferior cerebellar artery. The objective of the present study was to investigate the consequences of this cerebellar damage with regard to higher cognitive functions. On admission to the stroke unit, the patient presented with dysarthria, right-sided appendicular ataxia, gait ataxia, and right-sided horizontal nystagmus (National Institutes of Health Stroke Scale, NIHSS, score 4). When examined 10 days after his stroke using a set of neuropsychological tests, he showed a marked deficit in the ability to remember when and in which context he had previously encountered verbal material. This aspect of memory, so-called 'source memory', is known to be mediated mainly by frontal and medial temporal structures. The present case suggests the existence of a strong functional connectivity between cerebellum and cortical regions underlying specific memory processes. PMID- 20299800 TI - Hysterectomy and lower urinary tract symptoms: a nonrandomized comparison of vaginal and abdominal hysterectomy. AB - BACKGROUND/AIMS: It has been reported that lower urinary tract symptoms (LUTS) are more prevalent in patients who have undergone hysterectomy. However, the effects of surgical approach of hysterectomy on micturition have not been well documented. The aim of this study is to compare LUTS between patients who underwent vaginal and abdominal hysterectomy. METHODS: Prospective observational study among 430 patients undergoing vaginal or abdominal hysterectomy for benign disease other than genital prolapse. Participating patients completed a validated disease-specific questionnaire before surgery, 6 months and 3 years after surgery. RESULTS: 112 women underwent vaginal hysterectomy and 318 abdominal hysterectomy. After correction for differences in uterine size, descent of the uterus and other differences, LUTS were more common at 3 years after surgery following vaginal than following abdominal hysterectomy (OR 2.2, 95% CI 1.3-4.0). After adjustment for descent of the uterus, uteral size, parity and indication for hysterectomy, this difference was still statistical significant (adjusted OR 3.0, 95% CI 1.4-6.2). CONCLUSION: As compared to abdominal hysterectomy, LUTS appear to be more common following vaginal hysterectomy. PMID- 20299801 TI - Morphological and molecular modifications induced by different carbohydrate sources in Tuber borchii. AB - During the life cycle of mycorrhizal fungi, morphological, genetic and metabolic modifications are induced in the fungus and its symbiotic partner. These changes are influenced by environmental factors: light, gravity, oxygen, temperature, soil type, nutrients, root exudates and the presence of particular bacterial and perhaps fungal and viral populations in the mycorrhizosphere. To determine whether different carbohydrates lead to cell-signalling events and morphofunctional changes in cultured Tuber borchii mycelia, the expression level of genes involved in morphological modifications was investigated using a macroarray technique and real-time RT-PCR. The morphological study showed an increased growth of Tuber mycelia in glucose, while the hyphae were thinner and less branched in sucrose and maltose. This was accompanied by an upregulation of the genes involved in the general cell metabolism, detoxification processes, hyphal growth and cytoskeleton organization. Since glucose is also present in root exudates, the increased expression of these genes might support the hypothesis that glucose can act as a signal for the fungus to indicate the presence of the plant, and to trigger the complex symbiotic process. These mechanisms can lead to morphological modifications, including increased branching of the root which is necessary for the fungus to establish the symbiosis. PMID- 20299803 TI - Obesity-associated cognitive decline: excess weight affects more than the waistline. PMID- 20299802 TI - Longitudinal examination of obesity and cognitive function: results from the Baltimore longitudinal study of aging. AB - BACKGROUND: Obesity indices (i.e. BMI, waist-to-hip ratio) show differential relationships to other health outcomes, though their association to neurocognitive outcome is unclear. METHODS: We examined whether central obesity would be more closely associated with cognitive function in 1,703 participants from the Baltimore Longitudinal Study of Aging. RESULTS: Longitudinal mixed effects regression models showed multiple obesity indices were associated with poorer performance in a variety of cognitive domains, including global screening measures, memory, and verbal fluency tasks. Obesity was associated with better performance on tests of attention and visuospatial ability. An obesity index by age interaction emerged in multiple domains, including memory and attention/executive function. CONCLUSION: Obesity indices showed similar associations to cognitive function, and further work is needed to clarify the physiological mechanisms that link obesity to poor neurocognitive outcome. PMID- 20299804 TI - Size of Creutzfeldt-Jakob disease epidemic associated with cadaveric dura transplantation. AB - BACKGROUND: Ongoing surveillance following the 1996 Japanese nationwide survey on dural-graft-associated Creutzfeldt-Jakob disease (d-CJD) has found that, of all d CJD cases occurring globally, most patients were identified in Japan. Despite wide recognition that the epidemic is the consequence of shortcomings in the regulation of organ transplantation and the tardy decision-making by the Japanese health ministry, the size of the d-CJD epidemic remains unknown. METHODS: To estimate the overall size of the d-CJD epidemic, a mathematical model was constructed using data on 132 d-CJD patients from the Japanese nationwide surveillance system from 1996 to 2008. RESULTS: Our bayesian model predicted the size of the epidemic to be 163 patients (95% bayesian credible set: 147-183), suggesting that the probability of observing a total of 200 d-CJD patients in the future is low. Further, using a model which included a hypothetical 1987 ban on the use of dura mater, we estimated that the number of patients developing d-CJD would have been between 82 and 122, had Japan acted sooner to counteract the influx of tainted grafts. CONCLUSION: From a public health point of view, minimizing the number of patients exposed should be the highest priority in stemming future epidemics. PMID- 20299805 TI - Time of birth, residential solar radiation and age at onset of multiple sclerosis. AB - BACKGROUNDS/AIM: Gestational and early life events have been suggested to contribute to multiple sclerosis (MS) susceptibility. We assessed the effects of time and place of birth on the age at onset of MS symptoms. METHODS: We selected a national cohort of 967 veterans from the Multiple Sclerosis Surveillance Registry for whom month and season (time) of birth, and birthplace (city and state) were available. Multiple linear regression analyses were used to examine the association between time of birth, birthplace latitude and solar radiation, and the age at onset of MS symptoms among the study sample. RESULTS: Patients with a relapsing form of the disease (R-MS), who were born in winter and whose birthplace was in low solar radiation areas, had disease symptom onset on average 2.8 years earlier than those born in seasons other than winter and in medium- and high-solar radiation areas (p = 0.02). CONCLUSIONS: These results suggest that exposure early in life to geographical and seasonal factors, possibly related to the protective effect of sunlight, and thus vitamin D, is associated with a delay in MS symptom onset. Other larger studies are required to examine the period specific (from conception to adulthood) environmental factors that are associated with MS susceptibility. PMID- 20299806 TI - Cognitive impairment and associated factors among the elderly in the Shanghai suburb: findings from a low-education population. AB - OBJECTIVE: Our purpose was to investigate the prevalence of cognitive impairment and associated factors among elderly people in the Shanghai suburb. METHODS: A population-based survey was conducted for people aged 60 years and over in a community of 2 towns (Huaxin and Xujing) in Qingpu district, located in the western suburb of Shanghai. Face-to-face interviews were carried out to collect relevant information with prepared questionnaires. The Chinese version of the Mini-Mental State Examination was used to screen subjects with cognitive impairment, and the criteria of cognitive impairment were adjusted for education level. Univariate and multivariate logistic regression analyses were performed to evaluate factors putatively associated with cognitive impairment. RESULTS: There were 2,809 subjects (1,010 men and 1,799 women) aged 60 years and over (mean: 70.6, SD: 6.6) included in the study, and 198 people (42 men and 156 women) had cognitive impairment, with a prevalence of 7.0% (95% CI: 6.1-7.9) for both genders, 4.2% (95% CI: 3.6-4.8) for men and 8.7% (95% CI: 8.0-9.4) for women among the elderly. The prevalence rates of cognitive impairment increased with age. Although a number of factors were found to be significantly associated with the risk of cognitive impairment from the univariate analysis, only age (OR: 2.245, 95% CI: 1.755-2.872) and preferring a nonsalty diet (OR: 0.647, 95% CI: 0.460-0.912) were left in the final model of multivariate logistic regression analysis. CONCLUSION: The prevalence of cognitive impairment among the elderly in the Shanghai suburb is relatively high, compared with that previously reported from other areas in China, but lower than that from western countries. Factors associated with cognitive impairment need to be further investigated in the future. PMID- 20299807 TI - Development and validation of a self-administered questionnaire for myasthenia gravis patients. AB - BACKGROUND: To date, the investigation of the epidemiological profile of myasthenia gravis (MG) is sparse, and the influence of environmental and lifestyle factors on the occurrence of the disease remains thus unknown. The main aim of this study, which is part of a European collaborative project (EuroMyasthenia), was to develop a self-administered questionnaire to investigate these potential predisposing factors for MG. No instrument for investigating these particular factors has previously been designed for MG patients. MATERIAL AND METHODS: The questionnaire was developed in 3 stages: (1) devising a draft questionnaire based on questions derived from previously validated questionnaires and self-designed questions on MG characteristics; (2) testing the questionnaire on Norwegian MG patients (n = 57), and (3) assessing the content and criterion validity, and test-retest reliability, of the final questionnaire. RESULTS: The questionnaire was easy to use and showed good feasibility for MG patients. Psychometric evaluation established the validity and reliability of the self designed questions on MG characteristics. CONCLUSION: This is the first validated instrument developed to identify self-assessed environmental factors and potential predisposing factors for MG, and suitable for use in large-scale epidemiological studies. PMID- 20299808 TI - Systematic review of observational studies. PMID- 20299809 TI - Case-control studies: the importance of design and conduct. PMID- 20299810 TI - Design and methods of population surveys. PMID- 20299811 TI - Neuropsychobiological aspects, comorbidity patterns and dimensional models in borderline personality disorder. AB - Borderline personality disorder (BPD) is a comorbid and disabling condition with high prevalence in psychiatric settings. The pathogenesis of BPD involves complex interactions among genetic, neurobiological and environmental factors, resulting in multiple core symptom domains such as emotional dysregulation, impulse dyscontrol, aggression, cognitive dysfunctions and dissociative states. Neurobiological studies show that symptoms and behaviors of BPD are partly associated with alterations in glutamatergic, dopaminergic and serotonergic systems. In addition, neuroimaging studies in BPD patients indicate differences in the volume and activity of specific brain regions related to emotion and impulse control, such as the prefrontal and cingulate cortex, amygdala and hippocampus. Neurobiological alterations are related to cognitive disturbances in patients with BPD and neuropsychological tests have shown abnormalities of memory, attention, language, and executive functions. The aim of the present review is to provide an updated overview of the main neuropsychobiological aspects of BPD and their relation to clinical symptoms, comorbidity patterns and dimensional models. PMID- 20299812 TI - P300 and the stroop effect in overweight minority adolescents. AB - AIM: The goal was to examine the relationship between a risk factor for poor cognitive control and a health outcome of growing public significance--an excess body mass--among adolescents. METHODS: To this end, 109 adolescents aged 14-20 years were recruited and assigned to 1 of 4 groups defined by the crossing of the absence versus presence of a parental history (PH) of externalizing disorders with a body mass index (BMI) percentile (BMIP) < 85 versus > or = 85. The principal measure estimating cognitive control was the P300 event-related electroencephalographic response recorded during the Stroop task. RESULTS: The analyses revealed a synergistic interaction between BMIP rank, PH and trial type: the increase in P300 latency and the decrease in response accuracy, elicited by the presence of interfering information, were markedly greater in high-BMIP subjects with a PH of externalizing disorders than in the other subject groups. Analyses of a later component, the N450, previously associated with the Stroop interference effect, revealed no effect of BMI or PH. CONCLUSIONS: We conclude that subjects with both a PH of externalizing disorders and an excess BMI constitute a unique group that is less able to resolve cognitive conflict than others. The excessive delay in P300 evoked by conflicting response demands in these subjects may be a marker of a heritable factor that increases risk for both excess body mass and substance use disorders. PMID- 20299813 TI - Spatial learning and expression patterns of PP1 mRNA in mouse hippocampus. AB - BACKGROUND: Synaptic plasticity is believed to be the major cellular basis for learning and memory. Protein phosphorylation is a key process involved in changes in the efficacy of neurotransmission. In long-term changes synaptic plasticity is followed by structural plasticity and protein de novo synthesis. Such mechanisms are believed to build the basis of hippocampal learning and memory investigated in the Morris water maze (MWM) task. To examine the role of dephosphorylation during that model for spatial learning, we analyzed protein phosphatase 1 (PP1) expression in the hippocampus of mice at various stages of the task and in two groups with different learning abilities. METHODS: Mice were trained for 4 days with four trials each day in the MWM. For gene expression hippocampi were prepared 1, 6 and 24 h after the last trial of each day. PP1 and brain-derived neurotrophic factor (BDNF) mRNA levels were determined by quantitative real-time PCR. RESULTS: The task requirements themselves affected expression levels of both PP1 and BDNF. In contrast to BDNF, PP1 was differentially expressed during learning. Poorly and well performing mice differed significantly. When performance was poor the expression level of PP1 was higher. CONCLUSION: Present results add further in vivo evidence that not only phosphorylation but also dephosphorylation is a major mechanism involved in learning and memory. Therefore, inhibition of hippocampal phosphatase activity might improve learning and memory. PMID- 20299814 TI - The Bern psychopathology scale for the assessment of system-specific psychotic symptoms. AB - The translation from psychiatric core symptoms to brain functions and vice versa is a largely unresolved issue. In particular, the search for disorders of single brain regions explaining classical symptoms has not yielded the expected results. Based on the assumption that the psychopathology of psychosis is related to a functional imbalance of higher-order brain systems, the authors focused on three specific candidate brain circuitries, namely the language, and limbic and motor systems. These domains are of particular interest for understanding the disastrous communication breakdown during psychotic disorders. Core symptoms of psychosis were mapped on these domains by shaping their definitions in order to match the related brain functions. The resulting psychopathological assessment scale was tested for interrater reliability and internal consistency in a group of 168 psychotic patients. The items of the scale were reliable and a principal component analysis (PCA) was best explained by a solution resembling the three candidate systems. Based on the results, the scale was optimized as an instrument to identify patient subgroups characterized by a prevailing dysfunction of one or more of these systems. In conclusion, the scale is apt to distinguish symptom domains related to the activity of defined brain systems. PCA showed a certain degree of independence of the system-specific symptom clusters within the patient group, indicating relative subgroups of psychosis. The scale is understood as a research instrument to investigate psychoses based on a system-oriented approach. Possible immediate advantages in the clinical application of the understanding of psychoses related to system-specific symptom domains are also discussed. PMID- 20299816 TI - The extracellular matrix and cell migration. AB - As we know all too well, pancreatic cancer has a very poor prognosis largely due to its early tendency to invade, locally and distantly. Recently, scientists in the field have increasingly focused on the desmoplastic reaction, which is characteristic of most pancreatic cancers. This reaction is associated with proliferation of fibroblastic cells, sometimes outnumbering local tumor cells, and consists of abundant extracellular matrix (ECM) proteins. Importantly, the processes of invasion and metastasis take place within this tumor microenvironment. Stroma and tumor cells exchange signals to modify the local ECM, which subsequently stimulates cell migration and promotes proliferation and survival. Even though recognition of the significance of these microenvironment interactions exists, knowledge on the mechanisms of the interplay among pancreatic cells, myofibroblasts, and the ECM is lacking. Therefore, this 'Pancreatology and the Web' focuses on websites that provide information on the ECM and cell migration. and IAP. PMID- 20299815 TI - Radiofrequency coblation decreases blood loss during endoscopic sinonasal and skull base tumor removal. AB - BACKGROUND/AIMS: Minimizing bleeding during transnasal resections of sinonasal tumors is imperative for optimizing visualization and decreasing complications. The purpose of the present study was to determine whether radiofrequency coblation decreases blood loss during endoscopic tumor removal. METHODS: Sinonasal/skull base tumors treated in 2008 with endoscopic techniques were reviewed. The data collected included demographics, histopathology, technique, duration, complications and estimated blood loss (EBL). Full operative videoendoscopy was available in all cases and scored by the authors using the 11 point Wormald surgical field grading scale. RESULTS: Twenty-three patients (average age: 46 years) with sinonasal or skull base tumors treated with transnasal endoscopic techniques were identified. Coblation was used in 10 cases. The sinus/skull base tumors included were esthesioneuroblastoma (n = 6), melanoma (n = 3), squamous cell carcinoma (n = 3), inverted papilloma (n = 3), adenocarcinoma (n = 2), intracranial dermoid cyst (n = 2), adenoid cystic carcinoma (n = 1), craniopharyngioma (n = 1), fibromyxosarcoma (n = 1) and undifferentiated carcinoma (n = 1). The use of the coblation device was associated with a significant decrease in all categories including EBL (350 vs. 1,000 ml; p = 0.0001), EBL per operative time (66 vs. 166 ml/h; p = 0.0001) and Wormald grade (3.3 vs. 6.4; p = 0.0001). CONCLUSION: Radiofrequency coblation significantly decreased blood loss during endoscopic tumor removal and is a useful tool in the armamentarium of the endoscopic skull base surgeon. PMID- 20299817 TI - Primers on molecular pathways - cycling toward pancreatic cancer. AB - Human cells divide and proliferate during the early stages of life to support development, and throughout adult life to support normal cellular turnover. Each dividing cell follows an orderly and tightly regulated series of events known as the cell cycle. This process ensures proper cellular division that maintains DNA and chromosomal integrity and responds appropriately to external signals which communicate the level of demand for new cells. In cancer, genetic mutations leading to the overexpression of proteins which support cell cycle progression, or the downregulation of proteins involved in cell cycle inhibition contributes to the dysregulated cellular division and proliferation of malignant cells. The resulting uninhibited cellular proliferation provides ample opportunity for additional genetic mutations that lead to tumor progression. In the following review, we provide a brief introduction to the cell cycle and a discussion of the mechanism underlying the dysregulation of the cell cycle in human cancer. We pay particular attention to pancreatic adenocarcinoma, an aggressive tumor that has a 5-year survival rate of 3-5%, and is the fourth leading cause of cancer mortality in the US. and IAP. PMID- 20299818 TI - Diagnostic efficacy of the secretin stimulation test for the Zollinger-Ellison syndrome: an intra-individual comparison using different dosages in patients and controls. AB - BACKGROUND/AIMS: The secretin stimulation test is the principal diagnostic tool to identify Zollinger-Ellison syndrome (ZES). We investigated, by intra individual comparison, which dose of secretin results in the highest diagnostic efficacy to identify the ZES. METHODS: Fifty-seven paired secretin stimulation tests, using both 0.26 microg/kg and 0.78 microg/kg secretin, performed in 13 ZES patients and 12 controls, were analyzed and the findings confirmed in a validation cohort. RESULTS: A gastrin increase of >100 ng/l was found to be the most sensitive and specific criterion for a positive test. Higher gastrin increases after 0.78 microg/kg compared to 0.26 microg/kg secretin contributed to a slightly more sensitive (82.9 vs. 80.5%) but less specific (68.8 vs. 81.3%) test. A validation cohort, with 98 tests using 0.26 microg/kg secretin in 21 ZES patients and 39 controls, provided similar results. In ZES patients with normal fasting serum gastrin levels (<100 ng/l), there was no diagnostic benefit from the use of a higher secretin dose. CONCLUSIONS: The 0.26 microg/kg secretin stimulation test has the best diagnostic efficacy for the ZES. and IAP. PMID- 20299819 TI - Gemcitabine induces the VMP1-mediated autophagy pathway to promote apoptotic death in human pancreatic cancer cells. AB - BACKGROUND/AIM: Autophagy is a degradation process of cytoplasmic cellular constituents. We have described the vacuole membrane protein-1 (VMP1) whose expression triggers autophagy in mammalian cells. The aim of this study was to analyze the role of autophagy in human pancreatic cancer cell death. METHODS/RESULTS: Here we show that gemcitabine, the standard chemotherapy for pancreatic cancer, induced autophagy in PANC-1 and MIAPaCa-2 cells, as evidenced by the accumulation of acidic vesicular organelles, the recruitment of microtubule-associated protein-1 light chain-3, and electron microscopy. In addition, gemcitabine treatment induced early expression of VMP1 in cancer cells. Gemcitabine also induced apoptosis detected by morphology, annexin V-positive cells, and cleavage of caspase-3. Surprisingly, 3-methyladenine, an autophagy inhibitor, decreased apoptosis in gemcitabine-treated cells, showing that autophagy leads to cancer cell apoptotic death. Finally, VMP1 knockdown decreased autophagy and apoptosis in gemcitabine-treated cancer cells. CONCLUSIONS: The VMP1-autophagy pathway promotes apoptosis in pancreatic cancer cells and mediates gemcitabine-induced cytotoxicity. and IAP. PMID- 20299820 TI - Detection of gallstones in acute pancreatitis: when and how? AB - The detection and management of bile duct stones in acute pancreatitis have improved considerably. Now it is possible to identify non-invasively stones in the duct before definitive treatment. Recently new evidence has confirmed that the indication for early endoscopic sphincterotomy should be severe acute pancreatitis with evidence of bile duct obstruction. This review analyses the evidence that defines current best practice in this area. and IAP. PMID- 20299821 TI - Are there prognostic factors related to recurrence in pancreatic endocrine tumors? AB - AIMS: The aim of this study was to evaluate the rate, site, time of recurrence and prognostic factors related to the appearance of recurrences in patients affected by pancreatic endocrine tumors (PETs). METHODS: Data from 67 consecutive patients with PETs who underwent R0 resection were analyzed. The prognostic factors considered were: gender, age, type of tumor, presence of symptoms, size of tumor, tumor node metastasis (TNM) stage, WHO classification and adjuvant therapy. RESULTS: The recurrence rate was 24.6%, with a mean time of 7.3 +/- 4.5 years. The majority were in the liver (75% of cases) and were rarely local (25%). Univariate analysis of the prognostic factors showed that the risk of recurrences is significantly higher in PETs in MEN-1 syndrome, in tumor size > or =4 cm, in the presence of liver metastases, in TNM stages III-IV and, finally, in PD-Cas and WD-Cas. Multivariate Cox regression analysis showed that only MEN-1 syndrome and the WHO classification were independent predictors of an increased risk of recurrence. CONCLUSIONS: Several prognostic factors were related to recurrences in PETs. MEN-1 syndrome and the WHO classification can be considered independent factors of an increased risk of recurrence. and IAP. PMID- 20299822 TI - Investigations into the binding affinities of different human 5-HT4 receptor splice variants. AB - This study examined whether the drug-receptor-binding sites of 5 selected human 5 HT(4) receptor splice variants [h5-HT4(a), h5-HT4(b), h5-HT4(c), h5-HT4(d) and h5 HT4(g)] display preferential affinities towards agonists. The agonists selected on the basis of chemical diversity and clinical relevance were: 5-HT4 benzamides, renzapride, zacopride and prucalopride; the benzimidazolones, DAU 6236 and BIMU 1; the aromatic ketone, RS67333, and the indole carbazimidamide tegaserod. The rank order of affinities ranging across the splice variants was: tegaserod (pKi: 7.38-7.91) > or = Y-36912 (pKi: 7.03-7.85) = BIMU 1 (pKi: 6.92-7.78) > or = DAU 6236 (pKi: 6.79-7.99) > or = 5-HT (pKi: 5.82-7.29) > or = 5-MeOT (pKi: 5.64-6.83) > or = renzapride (pKi: 4.85-5.56). We obtained affinity values for the 5-HT4(b), (d) and (g) variants for RS67333 (pKi: 7:48-8.29), prucalopride (pKi: 6.86-7.37) and zacopride (pKi: 5.88-7.0). These results indicate that the ligands interact with the same conserved site in each splice variant. Some splice variants have a higher affinity for certain agonists and the direction of selectivity followed a common trend of lowest affinity at the (d) variant. However, this trend was not evident in functional experiments. Our findings suggest that it may be possible to design splice variant selective ligands, which may be of relevance for experimental drugs but may be difficult to develop clinically. PMID- 20299823 TI - Comparable sensitivities of urine cotinine and breath carbon monoxide at follow up time points of three months or more in a smoking cessation trial. AB - To control for likely overreporting of abstinence in clinical trials of smoking cessation aids, field convention demands the corroboration of subjects' self reports by a biochemical/pharmacological marker. It is, however, currently debated if urinary cotinine (UC), a metabolite of nicotine, should be preferred because of its higher sensitivity, although sample collection for and analysis of cotinine are much more expensive and work intensive than carbon monoxide (CO) measurements in exhaled air. In the present study, it turned out that UC was of only moderately higher sensitivity than CO (99.4% vs. 96.3%; p = 0.02), the difference being significant only at group sizes of >164. UC identified participants as smokers who escaped CO detection in 4.9% of the cases, whereas CO identified smokers who escaped UC detection in 2.7% of the cases (p = 0.014). Our findings suggest that the costs/disadvantages of using UC instead of CO may outweigh its benefit as a pharmacological marker of (non)smoking status. PMID- 20299824 TI - Role of the hypothalamo-pituitary-adrenal axis in the modulation of pollinosis induced by pollen antigens. AB - BACKGROUND: To clarify the mechanism of stress-induced modification of allergic diseases, we studied the effect of restraint stress on plasma levels of cytokines and the symptoms of pollinosis in mice. METHODS: The effects of restraint stress and the role of the hypothalamo-pituitary-adrenal axis (HPA-axis) in the development of pollen antigen-induced pollinosis were studied in control, hypophysectomized, adrenalectomized or ACTH-administered mice. Twenty days after sensitization, animals were subjected to mild restraint stress for 3 hours, and plasma levels of IFN-gamma, IL-10, and IgE were measured. We analyzed the incidence of sneezing and nasal rubbing in the sensitized animals. RESULTS: Plasma levels of IL-10 and IgE increased in the sensitized animals with a concomitant increase in the incidence of sneezing and nasal rubbing. The increases in plasma IgE, IL-10 and the incidence of sneezing and nasal rubbing were suppressed by restraint stress. Adrenalectomy increased IFN-gamma, inhibited the increase in plasma IL-10 and IgE, and suppressed the incidence of sneezing. In contrast, hypophysectomy increased plasma levels of IL-10, IFN-gamma, and IgE and the incidence of sneezing. Intraperitoneal administration of ACTH decreased IL-10 in plasma but increased IFN-gamma and suppressed the incidence of nasal rubbing. CONCLUSIONS: The present findings show that the HPA-axis and ACTH play important roles in the regulation of plasma cytokines and IgE thereby modulating symptoms of pollinosis. The results also suggest that a mild restraint stress suppresses the increase in Th2-dependent cytokines and IgE to reduce the symptoms of pollinosis. PMID- 20299825 TI - An 18-year follow-up of allergy development related to nasal metachromatic cell findings during infancy. AB - BACKGROUND: The ability to predict the development of allergic diseases in infants is important. Predictive biomarkers are wanted to improve the risk evaluation in addition to known heredity of allergy. Biomarkers taken during infancy need to be evaluated through longitudinal studies into adulthood. The objective of this study was to analyse the occurrence of metachromatic cells in the nasal mucosa during infancy (MC(infancy)) and evaluate the cells as predictive biomarkers of allergy development. METHODS: Previously, MC(infancy) occurrences were analysed in 64 infants with and without allergy heredity, and related to allergy development at 18 months and 6 years of age. In this third follow-up at 18 years of age, current allergy symptoms were analysed. MC(infancy) findings were related to the cumulative number of allergic subjects. The predictive values of MC(infancy) and known heredity were compared. RESULTS: The cumulative number of subjects with allergy was 46, probable allergy 5, and no allergy 13. Detected MC(infancy) predicted allergy with high accuracy (31/33), but negative MC(infancy) findings did not exclude the risk (15/31). In the group of allergic subjects positive MC(infancy) were found in 31/46 (67%), positive heredity in 37/46 (80%) and one/both factors positive in 43/46 (93%). Detection of MC(infancy) could precede the debut of allergy symptoms by many years. CONCLUSIONS: Detected MC(infancy) predicted allergy development, but absence of MC(infancy) did not exclude the risk, and therefore this biomarker was not found to be adequate. There is a further need to find biomarkers with high ability to both predict and exclude the risk. PMID- 20299826 TI - Antitussive effects of the leukotriene receptor antagonist montelukast in patients with cough variant asthma and atopic cough. AB - BACKGROUND: Chronic cough is the only symptom of cough variant asthma (CVA) and atopic cough (AC). Cysteinyl leukotriene receptor antagonists have been shown to be effective in CVA, but there are no reports on their effectiveness in AC. To evaluate the antitussive effect of montelukast, a leukotriene receptor antagonist, in CVA and AC. METHODS: Seventy-five patients with chronic cough received diagnostic bronchodilator therapy with oral clenbuterol hydrochloride for 6 days. Of the 75 patients, 48 and 27 met the simplified diagnostic criteria for CVA and AC, respectively. Patients with CVA were randomly divided into 3 groups: montelukast, clenbuterol, and montelukast plus clenbuterol. Patients with AC were randomly divided into 2 groups: montelukast and placebo. The efficacy of cough treatment was assessed with a subjective cough symptom scale (0 meant "no cough" and 10 denoted "cough as bad as at first visit"). The cough scale, pulmonary function test, and peak expiratory flow rate (PEF) were evaluated before and after 2 weeks of treatment. RESULTS: In patients with CVA, 2-week treatment with montelukast, clenbuterol, and montelukast plus clenbuterol all significantly decreased cough scores and treatment with montelukast plus clenbuterol was superior to treatment with montelukast alone. In the montelukast plus clenbuterol group, PEF values in the morning and evening significantly increased after 2 weeks compared with values before treatment. In patients with AC, scores on the cough scale did not differ significantly between the montelukast group and the placebo group. CONCLUSIONS: Montelukast was confirmed to suppress chronic non-productive cough in CVA, whereas it was not effective in non-productive cough in AC. PMID- 20299841 TI - When should nurse practitioners bill "incident to" a physician? PMID- 20299842 TI - SELECT: evaluation and implementation of clinical practice guidelines: a guidance document from the American Professional Wound Care Association. PMID- 20299843 TI - Insights into acinetobacter war-wound infections, biofilms, and control. AB - OBJECTIVE: Multidrug-resistant Acinetobacter baumannii is associated with a wide spectrum of infectious diseases ranging from nosocomial, community-acquired infections to those acquired following war or natural disaster. Especially to military personnel with war wounds, Acinetobacter infection is a formidable threat. The treatment has become exceedingly difficult, not only because the bacterium can develop extensive antimicrobial resistance but because it also forms biofilms that are resistant to host defense and antimicrobial treatment. Such causative factors as biofilm formation and resistance are highly likely to lead to nonhealing wounds. This review, although focused on A baumannii infections, aims to summarize what is known about immunization protection against wound biofilm infections and to apply such understanding in exploring the unknown area of war-wound infection protection. DATA SOURCES AND STUDY SELECTION: Publications were searched and selected through http://www.pubmed.gov by using the key words Acinetobacter baumannii, bacteria, war wounds, burn wounds, wound infections, biofilms, vaccines, and immunization. The literature selected was categorized according to the subheadings within this article. CONCLUSIONS: It is imperative to develop such effective measures as active and passive immunization to control multidrug-resistant and tenacious A baumannii infections and to prevent nonhealing wounds. The authors' understanding in immunization against burn wound-related infections by the model bacteria will facilitate research progress in the poorly explored area of immunization against war-wound biofilm infections. PMID- 20299844 TI - Transitional off-loading: an evidence-based approach to pressure redistribution in the diabetic foot. AB - PURPOSE: To enhance the learner's competence in providing pressure redistribution therapy for the diabetic foot. TARGET AUDIENCE: This continuing education activity is intended for physicians and nurses with an interest in skin and wound care. OBJECTIVES: After participating in this educational activity, the participant should be better able to: 1. Relate diabetic foot problems to the need for using off-loading devices. 2. Distinguish between the various types of dressings and off-loading devices used for diabetic foot wounds. 3. Apply the "transitional approach" to off-loading the diabetic foot. PMID- 20299846 TI - Checklists for compliance. PMID- 20299850 TI - The uniform data system for medical rehabilitation: report of patients with traumatic brain injury discharged from rehabilitation programs in 2000-2007. AB - OBJECTIVE: To provide benchmarking information for a large national sample of patients receiving inpatient rehabilitation after traumatic brain injury. DESIGN: Secondary data analysis from 893 medical rehabilitation facilities located in the United States that contributed information to the Uniform Data System for Medical Rehabilitation from January 2000 through December 2007. Variables analyzed included demographic information (age, sex, marital status, race or ethnicity, prehospital living setting, and discharge setting), hospitalization information (length of stay, program interruptions, payer, onset date, rehabilitation impairment group, Internation Classification of Diseases-9th revision codes for admitting diagnosis, and co-morbidities), and functional status information (FIM instrument [FIM] ratings at admission and discharge, FIM efficiency, FIM gain). RESULTS: Descriptive statistics from 101,188 patients showed length of stay decreasing from a mean of 22.7 (+/-20.5) days to 16.6 (+/-14.8) days during the 8 yr study period. FIM total admission and discharge ratings also decreased. Mean admission ratings decreased from 58.6 (+/-24.7) to 54.8 (+/-21.2). Mean discharge ratings decreased from 92.4 (+/-24.2) to 85.0 (+/-24.0). Accordingly, mean functional independence measure change decreased from 33.8 (+/-20.5) to 30.2 (+/ 18.4). The percentage of patients discharged to the community settings ranged from 81.3% in 2000 to 74.1% in 2007. All results are likely influenced by various policy changes affecting classification or documentation processes or both. CONCLUSIONS: National rehabilitation data from persons with traumatic brain injury in 2000-2007 indicate that patients are spending less time in an inpatient care setting than in the previous years and are experiencing improvements in functional independence during their stay. In addition, a majority of patients are discharged to community settings after inpatient rehabilitation. PMID- 20299851 TI - A review of driving simulator parameters relevant to the Operation Enduring Freedom/Operation Iraqi Freedom veteran population. AB - There is currently a pressing need for safe, reliable, cost-effective methods of evaluating driving ability. With recent improvements in virtual reality technology, driving simulators seem to offer a promising alternative to on-road methods of driving assessment. One population at risk for driving difficulties may be veterans returning from combat in Iraq or Afghanistan. The use of driving simulators to evaluate and remediate veterans' abilities to operate a motor vehicle is a rehabilitative goal. However, there are no consistent standardized procedures for determining safe from unsafe driving using driving simulators, which limit the clinical utility of this important tool. The purposes of this article are (1) to give the reader a better understanding of the parameters that are most commonly measured in the driving simulation literature and (2) to review parameters that are most relevant for the Operation Enduring Freedom/Operation Iraqi Freedom veteran population. PMID- 20299856 TI - Impaired information integration contributes to communication difficulty in corticobasal syndrome. AB - OBJECTIVE: To investigate the cognitive and neural correlates of discourse impairment in corticobasal syndrome (CBS). BACKGROUND: Difficulty communicating is a frequent clinical manifestation in patients with CBS. However, the mechanisms underlying this disabling problem are not well understood. METHODS: Twenty patients with CBS and 8 healthy seniors narrated a picture story. Narratives were analyzed for maintenance of the narrative theme, identification of the overall point of the story (global connectedness), and connectedness between consecutive events (local connectedness). Discourse measures were correlated with performance on cognitive tasks and with cortical atrophy as determined by magnetic resonance imaging voxel-based morphometry. RESULTS: Patients with CBS referred to the narrative theme significantly less frequently than controls. Global connectedness was intact in only 6 of 20 CBS patients (30%), but preserved in all controls. Local connectedness was significantly diminished in patients relative to controls. Discourse performance in CBS was related to tasks requiring higher-order integration of visual material, but not to basic visuospatial/visuoperceptual, language, or memory function. Discourse impairment was directly related to atrophy in the right parietal lobe and bilateral dorsolateral prefrontal cortex. CONCLUSIONS: Our findings suggest that impaired information integration in CBS, related to parieto-frontal disease, interferes with patients' ability to narrate a coherent story. PMID- 20299857 TI - Brazilian version of the Addenbrooke Cognitive Examination-revised in the diagnosis of mild Alzheimer disease. AB - OBJECTIVE: To investigate the accuracy of the Brazilian version of the Addenbrooke Cognitive Examination-revised (ACE-R) in the diagnosis of mild Alzheimer disease (AD). BACKGROUND: The ACE-R is an accurate and brief cognitive battery for the detection of mild dementia, especially for the discrimination between AD and frontotemporal dementia. METHODS: The battery was administered to 31 patients with mild AD and 62 age-matched and education-matched cognitively healthy controls. Both groups were selected using the Dementia Rating Scale and were submitted to the ACE-R. Depression was ruled out in both groups by the Cornell Scale for Depression in Dementia. The performance of patients and controls in the ACE-R was compared and receiver operator characteristic curve analysis was undertaken to ascertain the accuracy of the instrument for the diagnosis of mild AD. RESULTS: The mean scores at the ACE-R were 63.10+/-10.22 points for patients with AD and 83.63+/-7.90 points for controls. The cut-off score <78 yielded high diagnostic accuracy (receiver operator characteristic area under the curve=0.947), with 100% sensitivity, 82.26% specificity, 73.8% positive predictive value, and 100% negative predictive value. CONCLUSIONS: The Brazilian version of the ACE-R displayed high diagnostic accuracy for the identification of mild AD in the studied sample. PMID- 20299858 TI - Anxiety affects working memory only in left hemibody onset Parkinson disease patients. AB - OBJECTIVE: This investigation sought to examine the potential moderating influence of heightened anxiety on working memory in Parkinson disease (PD) patients. Further, we wanted to determine whether this moderating influence of anxiety differentially affects PD patients with left hemibody (LBH) versus right hemibody (RHB) onset of motor symptoms. BACKGROUND: Research has examined the neurocognitive effects of depression in PD. However, a paucity of research has examined the effects of heightened anxiety in PD. We predicted that LHB PD patients with heightened anxiety would perform worse on a measure of working memory than RHB PD patients. METHOD: A total of 59 PD patients completed the state-trait anxiety inventory and were also administered the digit span subtest of the Wechsler Memory Scale-III. RESULTS: The results supported the hypotheses, indicating that the LHB PD patients with heightened anxiety performed significantly worse than the RHB PD patients with heightened anxiety and the LHB PD patients with low anxiety. CONCLUSIONS: These findings suggest that left hemibody onset PD patients may experience more disability in their activities of daily living. Future research should explore whether differences also exist between PD patients with and without the diagnosed anxiety disorders. PMID- 20299859 TI - Verbal and visuospatial memory in lateral onset Parkinson disease: time is of the essence. AB - OBJECTIVE: This investigation sought to study immediate and delayed verbal and visuospatial recall in Parkinson disease (PD) patients with left hemibody (LHO) and right hemibody (RHO) onset of motor symptoms and to examine the role of mental processing speed in recall of this information. BACKGROUND: Research is mixed regarding material specific memory impairments in LHO and RHO PD. However, earlier research has not used a factorial approach in investigating material specific memory in LHO and RHO PD. We hypothesized that LHO PD patients would exhibit an increase in performance following the delayed verbal free recall trial and either decline or stability in performance on the delayed visuospatial free recall trial. The opposite pattern was hypothesized for RHO PD patients. METHOD: The Hopkins Verbal Learning Test-revised (HVLT-R) and the Brief Visuospatial Memory Test-revised (BVMT-R) were administered to a sample of 28 LHO PD patients and 36 RHO PD patients. The Stroop Color-word Test was administered as a measure of mental processing speed. RESULTS: The results indicated that the RHO group experienced a significant decline in performance on verbal free recall from the immediate to the delayed trials and a significant improvement in performance from the immediate to the delayed visuospatial free recall trials. Additionally, a significant negative correlation was found between mental processing speed and changes in recall from the immediate to the delayed conditions for the RHO group. CONCLUSIONS: These results indicate that the RHO PD group experienced a significant decline in verbal free recall and a significant improvement in visuospatial free recall from the immediate to the delayed trials and that the LHO PD patients experienced no significant changes. Further, mental processing speed appears to influence the recall of information from the immediate to the delayed conditions. PMID- 20299860 TI - Frontal assessment battery in patients with Parkinson disease in a Turkish population. AB - OBJECTIVE: The aims of this study were to assess frontal dysfunction in Turkish patients with idiopathic Parkinson disease (PD) by using frontal assessment battery (FAB), and to determine the relationship among FAB scores and education, Mini-Mental State Examination (MMSE), and severity of the disease. BACKGROUND: Cognitive impairment in patients with PD mainly involves executive dysfunction. Executive dysfunction is mainly related to the frontal lobes and their connections with the thalamus and basal ganglia. FAB is an easily applicable and valid test to examine frontal functions. METHOD: Forty patients diagnosed with PD and 52 healthy controls were included in the study. Age, sex, disease duration, and Unified Parkinson's Disease Rating Scale scores were noted. FAB and MMSE were administered to all participants. Both groups were compared according to FAB scores, MMSE, age, and education. RESULTS: FAB scores were significantly lower in patients with PD (P=0.00) than in healthy controls. In patients with PD, FAB scores were solely correlated with MMSE. In the subgroup analysis, the performance of patients with PD was worse than the healthy participants on similarities and fluency tasks. CONCLUSIONS: FAB scores are lower in Turkish patients with PD than in the healthy participants, and could be used for the evaluation of subtle cognitive deficits in these patients. PMID- 20299862 TI - Fragile X dementia Parkinsonism Syndrome (FXDPS). AB - BACKGROUND/OBJECTIVE: The fragile X-associated tremor/ataxia syndrome is characterized by intention tremor and ataxia in people who are premutation carriers of the Fragile X gene. Patients with this disorder might also demonstrate signs of dementia with parkinsonian features. We report a patient with dementia and parkinsonian signs who did not demonstrate an intention tremor or gait ataxia. METHODS: A 58-year-old woman who had 2 sons with fragile X retardation syndrome and was a carrier, developed progressive dementia, including impaired memory, executive dysfunction, nonfluent speech, and parkinsonian signs, but had no action-intention tremor and no gait ataxia. Magnetic resonance imaging revealed extensive abnormalities of the white matter. RESULTS: On post-mortem examination, 7 years after this evaluation, she demonstrated extensive subcortical white matter pallor (spongiosis) and widespread ubiquitin-positive intranuclear inclusions in both neurons and in protoplasmic astrocytes characteristic of fragile X-associated tremor/ataxia syndrome, but no spongiosis in the cerebellar peduncles a defining feature of this tremor/ataxia syndrome. CONCLUSIONS: Patients who present with dementia and signs of Parkinson syndrome, even in the absence of ataxia or intention tremor should be evaluated for this fragile X dementia parkinsonism syndrome. PMID- 20299861 TI - Improved language in a chronic nonfluent aphasia patient after treatment with CPAP and TMS. AB - OBJECTIVE: To present pretreatment and post-treatment language data for a nonfluent aphasia patient who received 2 treatment modalities: (1) continuous positive airway pressure (CPAP) for his sleep apnea, starting 1-year poststroke; and (2) repetitive transcranial magnetic brain stimulation (TMS), starting 2 years poststroke. BACKGROUND: Language data were acquired beyond the spontaneous recovery period of 3 to 6 months poststroke onset. CPAP restores adequate oxygen flow throughout all stages of sleep, and may improve cognition. A series of slow, 1 Hz repetitive TMS treatments to suppress a posterior portion of right pars triangularis has been shown to improve phrase length and naming in chronic nonfluent aphasia. METHOD: The Boston Diagnostic Aphasia Examination and Boston Naming Test were administered pre-CPAP, and after 2 to 5 months of CPAP. These same tests were administered pre-TMS, and at 3 and 6 months post-TMS, and again 2.4 years later. RESULTS: Post-CPAP testing showed increased Phrase Length, Auditory Comprehension, and naming Animals and Tools/Implements (Boston Diagnostic Aphasia Examination). Testing at 3 and 6 months post-TMS showed significant increase in Phrase Length, Auditory Comprehension, and Boston Naming Test compared with pre-TMS. These gains were retained at 2.4 years post-TMS. CPAP use continued throughout. CONCLUSIONS: Physiologic treatment interventions may promote language recovery in chronic aphasia. PMID- 20299863 TI - A cortically blind patient with preserved visual imagery. AB - BACKGROUND/OBJECTIVE: The loss or preservation of visual imagery in patients with cortical blindness may be helpful in resolving the controversial roles assigned by some researchers to the early visual cortex during the process of visual imagery. PATIENT AND METHODS: Here we report a patient with complete permanent cortical blindness coupled with denial of the blindness (Anton syndrome) as a result of bilateral occipital infarction. RESULTS: Interestingly, the patient's ability to visualize objects, color, and spatial imagery was preserved, although cerebral computed tomography, magnetic resonance imaging, and positron emission tomography scans detected what was likely complete bilateral damage to the primary visual cortex. CONCLUSIONS: Our findings may support the hypothesis that the primary visual cortex, in which retinal spatial geometry is preserved, is not critical for visual imagery. PMID- 20299864 TI - The amnesic syndrome of primary Whipple disease of the brain. AB - OBJECTIVE: To describe a case of primary Whipple disease (WD) of the brain, which may manifest as an amnesic syndrome. MATERIALS AND METHODS: A 46-year-old woman developed primary WD of the brain. The onset was characterized by a short-term amnesic syndrome for several months before the onset of generalized tonic-clonic seizures. Her amnesia was stable throughout her illness. RESULTS: Our patient had impairment of verbal and visual memory tasks with reduced learning. Her amnesic syndrome was secondary to asymmetric bilateral hippocampal atrophy with gliosis involving the mesial temporal structures-all secondary to primary WD of the brain. CONCLUSIONS: WD may present as an amnesic syndrome and needs to be thought of as a treatable cause of cognitive dysfunction in young adults. PMID- 20299865 TI - Nomophobia: the mobile phone in panic disorder with agoraphobia: reducing phobias or worsening of dependence? AB - OBJECTIVE: In this report, we present and discuss a hypothesis for the development, in individuals with panic disorder and agoraphobia, of dependence on his or her mobile phone (MP). BACKGROUND: This disorder, termed nomophobia, is a result of the development of new technologies. Nomophobia is considered a disorder of the modern world and refers to discomfort or anxiety caused by being out of contact with a MP or computer. It is the pathologic fear of remaining out of touch with technology. METHOD: We present, the case report of a patient who has continuously kept his MP with him since 1995 because of his overwhelming need to feel safe and to be able to immediately call emergency services and people he trusts should he feel sick. RESULT: The patient was treated with medication and cognitive-behavior psychotherapy. He has remained asymptomatic for 4 years. The patient showed significant medical improvement in his panic disorder and phobias, but there has been no change in his nomophobia. CONCLUSIONS: The case presented here illustrates the dependence of an individual with panic disorder on his MP. A specific approach for this dependence should be used in some panic disorder patients. PMID- 20299866 TI - Auditory hallucinations: nomenclature and classification. AB - INTRODUCTION: The literature on the possible neurobiologic correlates of auditory hallucinations is expanding rapidly. For an adequate understanding and linking of this emerging knowledge, a clear and uniform nomenclature is a prerequisite. The primary purpose of the present article is to provide an overview of the nomenclature and classification of auditory hallucinations. MATERIALS AND METHODS: Relevant data were obtained from books, PubMed, Embase, and the Cochrane Library. RESULTS: The results are presented in the form of several classificatory arrangements of auditory hallucinations, governed by the principles of content, perceived source, perceived vivacity, relation to the sleep-wake cycle, and association with suspected neurobiologic correlates. CONCLUSIONS: This overview underscores the necessity to reappraise the concepts of auditory hallucinations developed during the era of classic psychiatry, to incorporate them into our current nomenclature and classification of auditory hallucinations, and to test them empirically with the aid of the structural and functional imaging techniques currently available. PMID- 20299868 TI - Neonatal intensive care: dogma is for the dogs. PMID- 20299870 TI - Current world literature. PMID- 20299869 TI - Overview of chronic kidney disease in children. PMID- 20299898 TI - In defense of the DNP. PMID- 20299906 TI - Asthma in pregnancy: reading between the lines. PMID- 20299908 TI - Speak the language of autism. PMID- 20299910 TI - Climb to new educational heights. PMID- 20299911 TI - Smoking cessation: SNUB OUT CAD. PMID- 20299912 TI - A close-up view of flu. PMID- 20299954 TI - Casp8p41 expression in primary T cells induces a proinflammatory response. AB - OBJECTIVE: HIV infection of CD4 T cells can lead to HIV protease-mediated cleavage of procaspase 8 generating a novel, HIV-specific peptide called Casp8p41. Casp8p41 has at least two biologic functions: induction of cell death via mitochondrial depolarization and release of cytochrome C, as well as activation of nuclear factor kappa B (NFkappaB). We have previously shown that Casp8p41-induced NFkappaB activation enhances HIV LTR transcription and consequently increases HIV replication. Herein, we questioned whether Casp8p41 induced NFkappaB activation impacts the cytokine profile of cells expressing Casp8p41. DESIGN: Analysis of cells expressing Casp8p41 and HIV-infected T cells. METHODS: We assessed whether host genes are transcriptionally activated following Casp8p41 production, using microarray analysis, cytokine quantification, followed by western blot and flow cytometry. RESULTS: Microarray analysis identified 259 genes significantly upregulated following expression of Casp8p41. Furthermore, Casp8p41 expression in primary CD4 T cells results in increased production of interleukin (IL)-2, IL-15 and tumor necrosis factor (TNF), as well as IL-1RA; whereas levels of granulocyte macrophage colony-stimulating factor and interferon (IFN)-gamma were reduced in the Casp8p41 expressing cells. Intracellular flow cytometry confirmed the co-association of Casp8p41 with elevated TNF in HIV infected cells. CONCLUSION: These data indicate that the expression of Casp8p41 in HIV-infected CD4 T cells in addition to promoting apoptosis and enhancing HIV replication also promotes a proinflammatory cytokine milieu, which is characteristic of untreated HIV infection. PMID- 20299955 TI - Noncirrhotic portal hypertension in HIV-infected patients: unique clinical and pathological findings. AB - BACKGROUND: Liver disease of unknown cause in HIV-infected persons is rare but increasingly being reported. Noncirrhotic portal hypertension is the main feature in a subset of these patients, in whom gastrointestinal bleeding is the most frequent and potentially life-threatening clinical presentation. METHODS: We describe the epidemiological, clinical and histological features of 12 HIV positive individuals presenting with noncirrhotic portal hypertension. RESULTS: An interpretable liver biopsy was available in 11, and cirrhosis was absent in all patients. Three patients had nodular regenerative hyperplasia of the liver, whereas eight showed morphological features previously described as 'hepatoportal sclerosis'. In four of the later group, a distinctive lesion was noted characterized by massive absence of portal veins along with focal fibrous obliteration of small portal veins. All patients had been treated with didanosine for long periods and inflammatory and thrombotic processes hypothetically triggered by this purine analogue in the hepatic microvasculature might result in this form of obliterative portal venopathy. CONCLUSION: Noncirrhotic portal hypertension is a rare but unique entity presenting in HIV-positive individuals generally with prior prolonged exposure to didanosine, which shows an obliteration of portal veins as the most distinctive histological finding in the liver. PMID- 20299956 TI - Conjugate and polysaccharide pneumococcal vaccines do not improve initial response of the polysaccharide vaccine in HIV-infected adults. AB - This is a randomized trial to compare the immunoglobulin G response and the antibody avidity after two pneumococcal vaccinations, conjugated pneumococcal vaccine (CPV) and polysaccharide pneumococcal vaccine (PPV) 4 weeks after vs. PPV alone in 202 HIV-infected adults. There were no differences in the two strategies, either in the percentage of immunoglobulin G two-fold increase for the CPV included serotypes or immunoglobulin G two-fold increase, reaching the level of 1 microg/ml except for serotype 23F (26% responded after conjugated pneumococcal vaccine + PPV vs. 14% after PPV). No avidity increases were seen in any strategy. PMID- 20299957 TI - Lower atovaquone/proguanil concentrations in patients taking efavirenz, lopinavir/ritonavir or atazanavir/ritonavir. AB - HIV-infected travellers frequently use atovaquone/proguanil as malaria prophylaxis. We compared atovaquone/proguanil pharmacokinetics between healthy volunteers and HIV-infected patients taking efavirenz, lopinavir/ritonavir or atazanavir/ritonavir. The geometric mean ratio (95% confidence interval) area under the curve (AUC)0-->t for atovaquone relative to the healthy volunteers was 0.25 (0.16-0.38), 0.26 (0.17-0.41) and 0.54 (0.35-0.83) for patients on efavirenz, lopinavir/ritonavir and atazanavir/ritonavir, respectively. Proguanil plasma concentrations were also significantly lower (38-43%). Physicians should be alert for atovaquone/proguanil prophylaxis failures in patients taking efavirenz, lopinavir/ritonavir or atazanavir/ritonavir. PMID- 20299958 TI - Tuberculosis outcomes and drug susceptibility in individuals exposed to isoniazid preventive therapy in a high HIV prevalence setting. AB - OBJECTIVE: Despite World Health Organization recommendations, concerns about promoting resistance have impeded implementation of isoniazid preventive therapy (IPT) for tuberculosis (TB). We describe characteristics of TB in individuals previously exposed to IPT as part of 'Thibela TB', a cluster-randomized trial of community-wide IPT in gold miners in South Africa. DESIGN: Case series including participants who were dispensed IPT, attended at least one follow-up visit and were subsequently treated for TB. METHODS: TB episodes were detected through surveillance and through follow-up if IPT was stopped early. Drug susceptibility data were compared with TB episodes detected through surveillance in control clusters (where IPT use was minimal) and a laboratory substudy of mycobacterial sputum culture from TB suspects in control clusters. RESULTS: Among 126 eligible individuals (125 men, median age 43 years), median time from starting IPT to TB treatment was 316 days (interquartile range 174-491). Ninety-four of the 126 (75%) were first episodes. Eighty-nine of 103 (86%) tested HIV-infected, with the median CD4 cell count of 196 cells/microl (n = 51). Sixty-four of 108 (59%) with known treatment outcomes were cured or completed treatment. Among 71 isolates with drug susceptibility results available, 12.1% [95% confidence interval (CI) 5.0-23.3] and 7.7% (95% CI 0.2-36.0) from first and retreatment episodes, respectively, had isoniazid resistance, compared with 6.0% (95% CI 3.1-10.2) and 18.7% (95% CI 10.6-29.3) in control clusters and 11.8% (95% CI 8.2-16.3) among first TB episodes in the laboratory substudy. CONCLUSION: TB after recent IPT has prevalence of drug resistance similar to background and treatment outcomes typical of this setting. These data support wider implementation of IPT. PMID- 20299960 TI - An insight into the opening path to semi-open conformation of HIV-1 protease by molecular dynamics simulation. AB - Investigation of the opening process of HIV-1 protease is highly useful for understanding its functional mechanism and substrate/inhibitor binding dynamics, and for facilitating inhibitor drug design. Previous molecular dynamics simulations have revealed some opening paths and conformations, but they appear to be insufficient to explain some experimentally detected opening behaviors. We evaluated the possibility of the existence of alternative opening paths to the semi-open conformation by performing the molecular dynamics simulation of the early opening process of an inhibitor-free HIV-1 protease with explicit solvation. The closed form of the HIV-1 protease transforms to the semi-open form in 2500 ps via a path significantly different from those detected by other reported molecular dynamics simulations of the same protein. Some characteristics of this alternative path are consistent with the experimentally detected opening behavior. Our study combined with earlier studies suggested the existence of multiple opening paths. PMID- 20299959 TI - Long-term trends in adherence to antiretroviral therapy from start of HAART. AB - OBJECTIVE: People on antiretroviral therapy are likely to be required to maintain good adherence throughout their lives. We aimed to investigate long-term trends in highly active antiretroviral therapy (HAART) adherence to identify the main predictors and to evaluate whether participants experience periods of low adherence (95% adherence = 1.02 per year; 95% confidence interval (CI) 1.01-1.04; P = 0.0053]. Independent predictors of adherence were age, demographic group, calendar year period, drug regimen and previous virologic failures. The overall rate of at least one period of low adherence was 0.12 per person-year, but this rate decrease markedly over time to 0.01 in 2007/2008. CONCLUSION: Adherence, as measured by drug coverage, does not decrease on average over more than a decade from start of HAART. This is encouraging, because it shows that patients could potentially maintain viral suppression for many years. PMID- 20299961 TI - Tuberculosis and survival of HIV-infected individuals by time since seroconversion. AB - In a cohort of 1950 HIV-positive men with known dates of HIV seroconversion, 399 developed tuberculosis. Mortality rates following tuberculosis were greatly increased (hazard ratio, adjusted for age at seroconversion, 4.7, 95% confidence interval 3.7-6.1), and this ratio was similar at different times following seroconversion. Overall mortality was similar to that in western seroconverter cohorts with much lower rates of tuberculosis, suggesting that tuberculosis is more a marker of HIV progression than a cause of it. PMID- 20299962 TI - Changes in sexual behaviours: from secular trends to public health policies. AB - OBJECTIVE: To explore the relative contribution of secular trends and public health policies to changes in sexual behaviour. DESIGN: Three random probability surveys of the sexual behaviour of people aged 18-69 years were conducted in 1970, 1992 and 2006 in France. METHODS: Data of the 2006 survey (n = 12,364) were compared with those from two surveys carried out in 1970 (n = 2625) and 1992 (n = 20,055). RESULTS: Over the last decades, median age at first intercourse has decreased by 4 years for women (22.0 in the 1930s vs. 17.6 in the 2000s) and 1 year for men (18.1 vs. 17.2). Lifetime number of sexual partners increased for women (1.8 in 1970 vs. 4.4 in 2006), but not for men (11.8 vs. 11.6). At the same time, the proportion of respondents, especially women, who reported nonpenetrative sexual practices and considered sexual intercourse essential to well being was on the increase. These changes are mainly attributed to an increase in women's social status. A marked increase in condom use was observed following the first AIDS/HIV prevention campaigns in the 1980s. CONCLUSION: Public health interventions that are synergistic with trends in social norms are likely to be more effective than those that run counter to them. In France, sexual health and HIV prevention policies aimed at harm limitation appear to have chimed with secular trends. The evidence of greater diversification of sexual practices offers potential to increase the range of safer sex messages used in public health interventions. PMID- 20299963 TI - Ability of treatment week 12 viral response to predict long-term outcome in genotype 1 hepatitis C virus/HIV coinfected patients. AB - OBJECTIVE: Guidelines recommendation to extend treatment duration in genotype 1 hepatitis C virus (HCV)/HIV-coinfected patients who clear the virus later than treatment week 4 is not evidence-based. Our main objective was to study the ability of week 12 viral response [early virologic response (EVR)] to predict long-term outcome in patients treated for 48 weeks. DESIGN: Multicenter retrospective cohort analysis. METHODS: Genotype 1 HCV treatment-naive, HIV coinfected adult patients with compensated liver disease who started combination therapy with fixed-dose pegylated-interferon (pegIFN) alfa-2a or weight-based pegIFN alfa-2b plus ribavirin were included. Univariate and forward stepwise logistic regression analysis were used to identify predictors of sustained viral response (SVR) and relapse. RESULTS: By intention-to-treat analysis, 31.3% (87/278) of patients achieved an SVR. SVR rate was more than three-fold higher in patients who cleared the virus by week 12 of treatment compared with late responders. Among 123 end-of-treatment responders, 36 (29.3%) relapsed. Relapse risk increased in patients with cirrhosis, in those with ribavirin dose reductions and in late responders: more than 65% of patients who cleared the virus between weeks 12 and 24 relapsed following 48 weeks of treatment compared with 10% of those attaining a complete EVR (<15 IU/ml) at treatment week 12 (risk ratio 6.4, 95% confidence interval 2.9-14.4). CONCLUSION: Viral response at treatment week 12 is a strong predictor of long-term outcome. Genotype 1 HCV/HIV coinfected patients who achieve a complete EVR (<15 IU/ml) are at low risk of viral relapse after completing the standard 48 weeks of therapy. PMID- 20299966 TI - Impairment in kidney tubular function in patients receiving tenofovir is associated with higher tenofovir plasma concentrations. AB - Tenofovir (TFV) is a nucleotide analogue active against HIV and hepatitis B virus. Although TFV rarely affects the glomerular function, abnormalities in the kidney tubular function appear to be quite common. The relationship between TFV exposure and kidney tubular dysfunction (KTD) was examined prospectively in 92 HIV-infected individuals. Median TFV plasma trough concentration was higher in patients with KTD than in the rest (182 vs. 106 ng/ml; P = 0.001). This dose dependent effect further supports an involvement of TFV in KTD. PMID- 20299964 TI - Incidence and nature of cognitive decline over 1 year among HIV-infected former plasma donors in China. AB - OBJECTIVE: To quantify and characterize the nature of cognitive change over 1 year in a cohort of HIV-positive former plasma donors in rural China. DESIGN: The present study is an observational cohort study. METHODS: One hundred and ninety two HIV-positive and 101 demographically comparable HIV-negative individuals, all former plasma donors, who lived in a rural part of China, received comprehensive medical and neuropsychological examinations. At study entry, 56% of HIV-positive group was on combination antiretroviral treatment and 60.9% at follow-up. Multiple regression change score approach was used with the HIV-negative sample to develop norms for change that would be then applied to the HIV-positive participants. Follow-up test scores adjusted for the control group practice effect. RESULTS: Fifty-three HIV-positive individuals (27%) developed significant cognitive decline as compared with five (5%) HIV-negative individuals. Cognitive decline was predicted at baseline by AIDS status, lower nadir CD4, and worse processing speed; at follow-up, it was associated with lower current CD4 cell count and failure of viral suppression on combination antiretroviral treatment. Neuropsychological decline also was associated with decreased independence in activities of daily living. Using neuropsychological impairment scores that were corrected for 'practice' on repeated testing, we found that among the decliners, 41.5% (N = 22) had incident impairment, whereas 38% (N = 20) declined within the impaired range and another 20.7% (N = 11) declined within the normal range. CONCLUSION: The present study demonstrates that despite ongoing combination antiretroviral treatment, cognitive decline in HIV-positive people is common over a 1-year follow-up. Regression-based norms for change on western neuropsychological tests can be used to detect disease-related cognitive decline in a developing country. PMID- 20299965 TI - Cytokine signaling pathway polymorphisms and AIDS-related non-Hodgkin lymphoma risk in the multicenter AIDS cohort study. AB - BACKGROUND: Cytokine stimulation of B-cell proliferation may be an important causative mechanism for acquired immunodeficiency syndrome (AIDS)-related non Hodgkin lymphoma (NHL). The Epstein-Barr virus (EBV) may be a co-factor, particularly for primary central nervous system (CNS) tumors, which are uniformly EBV-positive in the setting of AIDS. Thus, we examined associations of genetic variation in IL10 and related cytokine-signaling molecules (IL10RA, CXCL12, IL13, IL4, IL4R, CCL5 and BCL6) with AIDS-related NHL risk and evaluated differences between primary CNS and systemic tumors. PATIENTS AND MATERIALS: We compared 160 Multicenter AIDS Cohort Study (MACS) participants with incident lymphomas, of which 90 followed another AIDS diagnosis, to HIV-1-seropositive controls matched on duration of lymphoma-free survival post-HIV-1 infection (N = 160) or post-AIDS diagnosis (N = 90). We fit conditional logistic regression models to estimate odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: Carriage of at least one copy of the T allele for the IL10 rs1800871 (as compared to no copies) was associated with decreased AIDS-NHL risk specific to lymphomas arising from the CNS (CC vs. CT/TT: OR = 0.3; 95% CI 0.1, 0.7) but not systemically (CC vs. CT/TT: OR = 1.0; 95% CI 0.5, 1.9) (Pheterogeneity = 0.03). Carriage of two copies of the 'low IL10' haplotype rs1800896_A/rs1800871_T/rs1800872_A was associated with decreased lymphoma risk that varied by number of copies (Ptrend = 0.02). None of the ORs for the other studied polymorphisms was significantly different from 1.0. CONCLUSION: Excessive IL10 response to HIV-1 infection may be associated with increased risk of NHL, particularly in the CNS. IL10 dysregulation may be an important causative pathway for EBV-related lymphomagenesis. PMID- 20299967 TI - Unusual five amino acid insert within subtype C HIV-1 envelope contributes to dual-tropism (X4R5). AB - During the course of HIV infection, some HIV-1 viruses switch from using the CCR5 (R5) coreceptor to using CXCR4 (X4). Here, we describe two subtype C isolates from a Zimbabwean patient that switched from using R5 to using both R5 and X4 with an accompanying addition of five amino acids to the V3 loop region of envelope. The insert appears to be derived from the human genome rather than a duplication within HIV-1. PMID- 20299968 TI - Cerebrospinal fluid in HIV-1 systemic viral controllers: absence of HIV-1 RNA and intrathecal inflammation. AB - BACKGROUND: A subset of HIV-infected patients, termed 'elite' viral controllers, maintain undetectable plasma HIV RNA levels in the absence of therapy. In this group, host-mediated viral control may be accompanied by chronic systemic inflammation. It is unknown whether either infection or chronic inflammation is present within the central nervous system of these individuals. METHODS: Cross sectional analysis compared cerebrospinal fluid (CSF) HIV RNA and biomarkers of intrathecal inflammation in eight controllers (plasma HIV RNA levels <50 copies/ml) with 26 HIV-uninfected individuals, 25 untreated individuals HIV infected, viremic individuals, and 23 HIV-infected individuals with treatment mediated viral suppression (plasma HIV RNA levels <50 copies/ml). RESULTS: All controllers had CSF HIV RNA levels below 2.5 copies/ml. CSF white blood cell (WBC) counts and CSF: plasma albumin ratios in the controllers were similar to those in both HIV-uninfected individuals and antiretroviral therapy-suppressed HIV-infected individuals. CSF neopterin, MCP-1, and IP-10 concentrations were also not different in the controllers from either HIV-uninfected or treated HIV infected individuals. CONCLUSION: The character of CSF HIV infection and degree of immunoactivation in controllers is comparable to that of HIV-uninfected and antiretroviral therapy-suppressed HIV-infected individuals, but distinct from that of untreated, viremic HIV-infected individuals. PMID- 20299969 TI - Cleidocranial dysplasia with severe parietal bone dysplasia: a new (p.Val124Serfs) RUNX2 mutation. PMID- 20299970 TI - Mitomycin C does not inhibit exacerbation of granular corneal dystrophy type II induced by refractive surface ablation. AB - PURPOSE: To evaluate the effect of mitomycin C (MMC) on the exacerbation of corneal opacity that occurs in patients with granular corneal dystrophy type II (GCD II) after refractive corneal surface ablation. METHODS: Ten eyes of patients with GCD II who underwent refractive corneal surface ablation with MMC were compared with 10 eyes that were not treated with MMC. Best spectacle-corrected visual acuity, the degree of corneal opacity, and contrast sensitivity were evaluated at least 3 years after surgery. Corneal opacities were quantified using Pentacam densitometry maps. RESULTS: No measured between-group value showed a statistically significant difference. CONCLUSION: Simultaneous application of MMC does not prevent exacerbation of GCD II after refractive corneal surface ablation. PMID- 20299971 TI - Extended long-term results of penetrating keratoplasty for keratoconus. AB - PURPOSE: To investigate the extended long-term results of penetrating keratoplasty (PK) for keratoconus. METHODS: The subjects were all patients with clinical keratoconus who underwent initial PK at University of Tokyo from 1971 to 1990 and whose medical records were available. Data were retrieved from the medical records. Kaplan-Meier survival analysis was performed to estimate the cumulative probability of immune reaction-free grafts and graft survival. RESULTS: One hundred twenty-five eyes in 125 patients met the entry criteria. The average age at the time of PK was 25.0 +/- 8.9 years. With an average follow-up period of 15.3 +/- 9.7 years, 12 eyes (9.6%) experienced rejection and 5 eyes (4.0%) experienced graft failure. Average best-corrected visual acuity in logarithm of the minimum angle of resolution at preoperation, 10, 20, and 25 years after surgery was 1.54 +/- 0.68, 0.06 +/- 0.22, 0.03 +/- 0.17, and 0.14 +/- 0.42, respectively. The cumulative probability of graft survival at 10, 20, and 25 years after PK was 98.8%, 97.0%, and 93.2%, respectively. CONCLUSIONS: Recovery of visual acuity was good after PK for keratoconus in an extended follow up. The graft survival rate, however, gradually decreased 20 years after PK. PMID- 20299972 TI - Comparison between normal values of 2- and 5-minute Schirmer test without anesthesia. AB - PURPOSE: To compare the 2- and 5-minute Schirmer test I (test without anesthesia) in healthy individuals so as to exploit the possibility of using the 2-minute instead of the 5-minute test. MATERIAL AND METHOD: 162 healthy (81 males and 81 females) individuals (without dry eye symptoms and free of pathology affecting tear secretion and tear drainage), aged between 20 and 85 years, were recruited in the study (3 age-groups: 20-45, 46-65, and 66-85 years). Schirmer test I (test without topical anesthesia) was performed in both eyes simultaneously. The values of tear secretion were recorded in 2 and 5 minutes and compared in relation to age and gender. The patients were asked to comment on the duration and the discomfort they felt. RESULTS: In 2 minutes, the average tear secretion was 12.71 +/- 2.47 mm (mean +/- SD) for the right eyes and 12.62 +/- 2.09 mm for the left eyes and in 5 minutes, 16.74 +/- 3.59 and 16.831 +/- 3.38 mm, respectively. For confidence interval of 99%, the mean values of tear secretion, in individuals who were expected to have normal secretion, were higher than 10 mm in 2 minutes and higher than 13 mm in 5 minutes (significance level 1% or a = 0.01). Only 5.55% of the eyes presented values <10 mm (7-9.5 mm) in the 2-minute test and values <13 mm (8.5-12.5 mm) in the 5-minute test. There was no significant difference in tear secretion between males and females, between the different age-groups, and between right and left eyes. All the examined individuals expressed their negative comments and considered the test as an unpleasant procedure and consequently preferred the shorter possible duration. CONCLUSION: The 2-minute test is more acceptable by both the examiners and the examined individuals and may be used, in respect to the above results, as an alternative of the 5-minute test. Normal individuals tend to have Schirmer test I values > or = 10 mm in 2 minutes, irrespective of age and gender. PMID- 20299973 TI - Effect of incision width on graft survival and endothelial cell loss after Descemet stripping automated endothelial keratoplasty. AB - PURPOSE: To assess the effect of incision width (5.0 and 3.2 mm) on graft survival and endothelial cell loss 6 months and 1 year after Descemet stripping automated endothelial keratoplasty (DSAEK). METHODS: One hundred sixty-seven subjects with endothelial decompensation from a moderate-risk condition (principally Fuchs dystrophy or pseudophakic corneal edema) underwent DSAEK by 2 experienced surgeons. The donor was folded over and inserted with single-point fixation forceps. This retrospective analysis assessed graft survival, complications, and endothelial cell loss, which was calculated from baseline donor and 6-month and 1-year postoperative central endothelial images evaluated by an independent specular microscopy reading center. RESULTS: No primary graft failures occurred in either group. One-year graft survival rates were comparable (98% vs 97%) in the 5.0- and 3.2-mm groups, respectively (P = 1.0). Complications included graft dislocation, graft rejection episodes, and elevated intraocular pressure and occurred at similar rates in both groups (P > or = 0.28). Pupillary block glaucoma did not occur in either group. Mean baseline donor endothelial cell density did not differ: 2782 cells per square millimeter in the 5.0-mm (n = 64) and 2784 cells per square millimeter in the 3.2-mm (n = 103) groups. Percent endothelial cell loss was 27% +/- 20% (n = 55) versus 40% +/- 22% (n = 71; 6 months) and 31% +/- 19% (n = 45) versus 44% +/- 22% (n = 62; 12 months) in the 5.0- and 3.2-mm incision groups, respectively (both P < 0.001). CONCLUSIONS: One year after DSAEK, overall graft success was comparable for the 2 groups; however, the 5.0-mm incision width resulted in substantially lower endothelial cell loss at 6 and 12 months. PMID- 20299974 TI - Straylight measurements in contact lens wear. AB - PURPOSE: (1) To quantify the effect of contact lens wear on straylight in rigid and soft contact lens wearers and (2) to relate findings to morphological changes and subjective complaints. METHODS: Straylight was measured using the Oculus C Quant during contact lens wear and after contact lens removal in 30 rigid contact lens wearers and 30 soft contact lens wearers. Semi-quantitative (0-4) slit-lamp grading of anterior segment changes using Efron grading scales and contact lens characteristics were performed. Subjects answered a straylight questionnaire. RESULTS: Soft contact lens wearers had a mean straylight of logarithmic value of the straylight parameter [log(s)] = 0.934 during contact lens wear and after contact lens removal [comparable to log(s) = 0.938 of age-matched normal eyes]. Rigid contact lens wearers had a mean straylight during contact lens wear of log(s) = 1.167. After contact lens removal, log(s) significantly decreased to 0.997 (P < 0.01). Straylight values with rigid contact lenses were strongly increased (P < 0.001) compared with age-matched normal eyes; after contact lens removal, these values decreased but remained elevated. Straylight in rigid contact lens wearers correlated with the amount of deposits on the contact lens (P < 0.01) but not with other variables of the contact lens score. The questionnaire showed more straylight complaints in rigid contact lens wearers than in soft contact lens wearers (P < 0.01). CONCLUSIONS: Rigid contact lens wear leads to increased straylight during contact lens wear and after contact lens removal. This may be because of subclinical effects of contact lens wear on the cornea and is not seen in soft contact lens wearers. PMID- 20299975 TI - Descemet stripping automated endothelial keratoplasty in eyes with previous trabeculectomy and tube shunt procedures: intraoperative and early postoperative complications. AB - PURPOSE: To evaluate the intraoperative and early postoperative outcomes of Descemet stripping automated endothelial keratoplasty (DSAEK) in patients with previous glaucoma filtering surgeries. METHODS: A retrospective review of all DSAEK surgeries performed at one center comparing complications of DSAEK in eyes with previous glaucoma filtering procedures (study eyes) with a time-matched group of all other DSAEK cases (control eyes). RESULTS: There were 28 study eyes, 19 with previous trabeculectomies and 9 with previous glaucoma drainage devices (GDDs) and 431 control eyes. Study group intraoperative complications included 1 compromised bleb and 1 loss of donor tissue because of traumatic manipulation. One intraoperative complication, a perforation of the donor tissue, occurred in the control group. Venting stab incisions were used more often in study eyes (n = 5; 18%) than in control eyes (n = 12; 4.4%) (P = 0.002). GDD tubes were trimmed in 2 eyes (22%). No intraoperative manipulations were used to occlude the glaucoma filters or tubes. Postoperative complications in the study group included 1 dislocation (3.6%) and 1 decentered graft (3.6%) and 1 eye with loss of pressure control (3.6%), whereas in the control group, there were 10 dislocations (2.3%) and 1 decentered graft (0.2%) (P = 0.267 for dislocations and P = 0.118 for decentered grafts). One episode of pupillary block (0.2%) occurred in the control group, and none occurred in the study group. No primary graft failures occurred in either group. CONCLUSIONS: DSAEK surgeries in eyes with previous glaucoma filtering procedures were performed without primary graft failure and with reasonably low dislocation (3.6%) and graft decentration (3.6%) rates. Although the intraoperative complication rate for the study group (7.1%) was higher than the rate for the control group (0.23%), excellent early postoperative outcomes can be achieved when DSAEK is performed in eyes with previous trabeculectomies and GDDs. PMID- 20299976 TI - In vivo confocal microscopic findings of 2 patients with Bietti crystalline corneoretinal dystrophy. AB - PURPOSE: To describe the clinical and in vivo confocal microscopic findings of the cornea in 2 patients with Bietti crystalline corneoretinal dystrophy using Heidelberg Retina Tomograph II Rostock Cornea Module. METHODS: Two women 25 and 33 years of age underwent ophthalmologic assessment, including fundus photography, optical coherence tomography, fluorescein angiography, electroretinography, and in vivo confocal microscopy. RESULTS: Slit-lamp examination revealed crystalline deposits at the superior limbus of the cornea in both of the subjects. Fundus examination disclosed numerous glistening yellowish white crystalline deposits scattered throughout the posterior pole and midperipheral retina, retina pigment epithelium and choriocapillaris atrophy; pigment clumping; and retinal scarring. Optical coherence tomography demonstrated hyperreflective red and white areas corresponding to the crystalline deposits in the retinal pigment epithelium-choriocapillaris complex. In vivo confocal microscopy of the superior paralimbal area showed randomly oriented needle-shaped or rod-shaped crystals up to 40 microm in length and 4-8 microm in width in the epithelium and the stroma. In other areas, the epithelium, stroma, and endothelium had normal appearance with no deposits. CONCLUSIONS: In vivo confocal microscopy is a noninvasive examination technique that shows clearly the corneal crystals located mainly in the superior paralimbal area in Bietti crystalline corneoretinal dystrophy, which can easily be missed even by an experienced ophthalmologist and therefore may aid further in the diagnosis. PMID- 20299977 TI - Midterm outcomes of autologous cultivated limbal stem cell transplantation with or without penetrating keratoplasty. AB - PURPOSE: To report the midterm outcomes of autologous limbal stem cell transplantation cultivated on amniotic membrane (AM) with or without subsequent penetrating keratoplasty (PKP) in patients with total unilateral limbal stem cell deficiency (LSCD). METHODS: Eight eyes of 8 consecutive patients with unilateral total LSCD underwent autologous limbal stem cell transplantation cultivated on AM. Four eyes underwent subsequent optical PKP. Main outcome measures were corneal vascularization and transparency. RESULTS: The patients were followed for 34.0 +/- 13.5 months (6-48 months). Seven cases had a stable corneal epithelium with marked decrease in opacification and vascularization. Progressive sectorial conjunctivalization was evident in all cases with subsequent PKP at the last follow-up. Primary failure was observed in one case because of exposure. CONCLUSIONS: Transplantation of autologous stem cells cultivated on AM with or without subsequent PKP seems to be an effective way for visual rehabilitation in total LSCD. More work with more cases and longer follow-up are needed to optimize this procedure to provide and maintain an adequate supply of limbal stem cells in these patients. PMID- 20299978 TI - The I allele of the angiotensin converting enzyme I/D polymorphism confers protection against coronary artery disease. AB - BACKGROUND: Mutations in genes regulating lipid metabolism, vasoactivity, and coagulation are important modulators of coronary artery disease (CAD). OBJECTIVE: This study investigated the association between allelic variants of the angiotensin converting enzyme (ACE), methytetrahydrofolate reductase, plasminogen activator inhibitor-1 and factor V genes and CAD. METHODS: Clinical, biochemical, and angiographic information were collected from 300 patients who underwent cardiac catheterization and their DNA was genotyped by restriction fragment length polymorphism. RESULTS: The frequency of the D allele of the ACE gene was significantly higher than the I allele in patients with more than 70% stenosis in any vessel. Among patients with more than 70% stenosis, carriers of the D allele were 2.8 times more likely to be males. The presence of the ACE I allele was negatively associated with CAD with (P=0.02 ,OR=0.38.) CONCLUSION: This study describes a protective role of the ACE I allele in individuals who may be at risk of developing CAD. PMID- 20299980 TI - Assessment of tissue characteristics of noncalcified coronary plaques by 64-slice computed tomography in comparison with integrated backscatter intravascular ultrasound. AB - BACKGROUND: The ability of 64-slice computed tomography (CT) angiography to differentiate plaque types remains unclear. We evaluated whether the density of noncalcified coronary plaques by 64-slice CT angiography correlates with plaque components assessed by integrated backscatter intravascular ultrasound (IB-IVUS). METHODS: Eighty-six patients [stable angina/acute coronary syndrome (ACS) 67/19, mean age 62+/-11 years] who showed significant coronary artery stenosis (> or =50% diameter stenosis) by 64-slice CT angiography underwent coronary angiography and were evaluated using IB-IVUS. RESULTS: A total of 92 noncalcified coronary plaques on CT angiography were evaluated with IB-IVUS. There was a positive correlation between CT density and calcified tissue content (r=0.41, P<0.001). However, the CT density of plaques did not correlate with other tissue components. Patients with ACS showed more lipid (43.1+/-13.2 vs. 35.8+/-13.5, P=0.03) and less soft fibrous tissue (50.5+/-11.7 vs. 56.5+/-12.0, P=0.05) by IB IVUS than those with stable angina. However, the mean CT density of plaques in ACS was not different from that in stable angina (140.6+/-88.5 vs. 113.1+/-80.9, P=0.19). CONCLUSION: Except for calcified tissue, CT angiography failed to differentiate plaque types of noncalcified tissue. Therefore, the role of 64 slice CT angiography in identifying lipid-rich plaques remains limited. PMID- 20299979 TI - Increased expression of plasminogen activator inhibitor type-1 (PAI-1) in HEPG2 cells induced by insulin mediated by the 3'-untranslated region of the PAI-1 gene and its pharmacologic implications. AB - OBJECTIVE: Insulin increases, through several molecular mechanisms, expression of plasminogen activator inhibitor-1 (PAI-1), the major physiologic inhibitor of fibrinolysis. This phenomenon has been implicated as a cause of accelerated coronary artery disease and the increased incidence of acute coronary syndromes associated with type 2 diabetes. We have previously reported that physiologic and pharmacologic concentrations of insulin induce PAI-1 synthesis in human HepG2 cells and that simvastatin can attenuate its effects. This study was performed to further elucidate mechanisms responsible for the insulin-induced PAI-1 production. METHODS: Concentrations of PAI-1 mRNA were determined by real-time PCR, and PAI-1 protein was assayed by western blotting. PAI-1 promoter (-829 to +36 bp) activity was assayed with the use of luciferase reporter assays. The potential role of the 3'-untranslated region (UTR) in the PAI-1 gene was assayed with the use of luciferase constructs containing the 3'-UTR. Oxidative stress was measured by loading cells with carboxy-2,7 dichlorodihydrofluorescein. RESULTS: Insulin increased PAI-1 promoter activity, PAI-1 mRNA, and accumulation of PAI-1 protein in the conditioned media. Insulin-inducible PAI-1 promoter activity was attenuated by simvastatin. Experiments performed with luciferase reporters containing the 3'-UTR showed that insulin increased luciferase activity through this region. Insulin also increased oxidative stress. Both insulin-inducible luciferase activity through the 3'-UTR and oxidative stress were attenuated by simvastatin. CONCLUSION: Insulin can increase PAI-1 expression through multiple mechanisms including induction mediated by the 3'-UTR of the PAI-1 gene. Accordingly, beneficial pleiotropic effects of statins on coronary artery disease may be attributable, in part, to attenuation of overexpression of PAI-1 mediated by the 3'-UTR in syndromes of insulin resistance (such as the metabolic syndrome) and type 2 diabetes. PMID- 20299981 TI - Validation of a strategy to diagnose coronary artery disease and predict cardiac events in high-risk renal transplant candidates. AB - BACKGROUND: We validated a strategy for diagnosis of coronary artery disease (CAD) and prediction of cardiac events in high-risk renal transplant candidates (at least one of the following: age > or =50 years, diabetes, cardiovascular disease). METHODS: A diagnosis and risk assessment strategy was used in 228 renal transplant candidates to validate an algorithm. Patients underwent dipyridamole myocardial stress testing and coronary angiography and were followed up until death, renal transplantation, or cardiac events. RESULTS: The prevalence of CAD was 47%. Stress testing did not detect significant CAD in 1/3 of patients. The sensitivity, specificity, and positive and negative predictive values of the stress test for detecting CAD were 70, 74, 69, and 71%, respectively. CAD, defined by angiography, was associated with increased probability of cardiac events [log-rank: 0.001; hazard ratio: 1.90, 95% confidence interval (CI): 1.29 2.92]. Diabetes (P=0.03; hazard ratio: 1.58, 95% CI: 1.06-2.45) and angiographically defined CAD (P=0.03; hazard ratio: 1.69, 95% CI: 1.08-2.78) were the independent predictors of events. CONCLUSION: The results validate our observations in a smaller number of high-risk transplant candidates and indicate that stress testing is not appropriate for the diagnosis of CAD or prediction of cardiac events in this group of patients. Coronary angiography was correlated with events but, because less than 50% of patients had significant disease, it seems premature to recommend the test to all high-risk renal transplant candidates. The results suggest that angiography is necessary in many high-risk renal transplant candidates and that better noninvasive methods are still lacking to identify with precision patients who will benefit from invasive procedures. PMID- 20299982 TI - Evaluating cancer epidemiologic risk factors using multiple primary malignancies. AB - BACKGROUND: Several authors have proposed the use of patients with double primary malignancies affecting the same or contralateral organ as a genetically enriched resource of cases for epidemiologic case-control studies in cancer. Such an approach is based on the assumption that the factors that increase the risk of a second primary are the same ones which influence the risk of a first primary. The advantages for statistical power are premised on the assumption that relative risks in survivors of a first primary cancer are similar to relative risks in the unaffected population. We explore these assumptions theoretically and empirically using published data from breast cancer studies involving bilateral breast cancer. METHODS: We conducted a literature review to identify case-control studies of variants in 4 genes known to affect breast cancer risk: CHEK2*1100delC; multiple variants in BRCA1 and BRCA2; and FGFR2 rs2981582. Summary odds ratios were obtained for each of 3 study designs: a conventional case-control design, the design comparing bilateral cases with unilateral controls, and the design comparing bilateral cases with population controls. RESULTS: The data show strong patterns of steadily increasing prevalence of risk factors from healthy controls to primary cases to bilateral cases, as expected. Relative risks in survivors of unilateral breast cancer are either the same as in the general population, or modestly attenuated. CONCLUSIONS: Patients with double primary malignancies are a very important underused resource for cancer epidemiologic investigation. Such patients are especially useful for broad genome wide discovery studies, and for studies of rare, strong risk factors such as high penetrance genes. PMID- 20299983 TI - A simplified risk score to predict difficult intubation: development and prospective evaluation in 3763 patients. AB - BACKGROUND AND OBJECTIVE: Despite the presence of numerous preoperative tests to predict a difficult airway, there is no reliable bedside method. The aim of this study was to create and verify a simplified risk model with an acceptable discriminating power. METHODS: A total of 3763 patients from two university hospitals were screened for potential risk factors for difficult intubation, defined as needing additional technical or human resources, more than three attempts or duration more than 10 min. A random sample (n = 2509) was subjected to multivariate stepwise logistic regression analysis, and the most powerful independent risk factors were used to build a simplified model that was applied to a validation dataset (n = 1254). RESULTS: The following factors (odds ratio) were associated with a difficult intubation: presence of upper front teeth (3.61), history of difficult intubation (2.88), any Mallampati status different from '1' (2.55) or equal to '4' (1.91) and mouth opening less than 4 cm (1.80). The discriminating power of the score was 0.72 (95% confidence interval 0.63 0.81). The likelihood for a difficult intubation increases continuously from 0 (when no risk factor is present) to 2, 4, 8 and 17%, when one, two, three and more than three factors are present. CONCLUSION: The new simplified multivariate risk score for difficult intubation may prove to be useful in clinical practice for predicting a difficult airway. Presence of upper front teeth, a history of difficult intubation, any Mallampati status different from '1' and equal to '4' and mouth opening less than 4 cm are independent risk factors for difficult endotracheal intubation. With each of these risk factors, the likelihood increases from 0 (when no risk factor is present) to 17% (when four or five factors are present). PMID- 20299984 TI - N-acetylcysteine does not prevent renal dysfunction after off-pump coronary artery bypass surgery. AB - BACKGROUND AND OBJECTIVE: Coronary artery bypass graft surgery in high-risk patients may be associated with postoperative renal dysfunction. N-Acetylcysteine is a powerful antioxidant and has been used to prevent contrast-induced renal dysfunction. The efficacy of N-acetylcysteine in preventing postoperative renal dysfunction following off-pump coronary artery bypass graft surgery was studied. METHODS: A prospective, randomized, controlled study was conducted in patients undergoing off-pump coronary artery bypass graft. The study group (37 patients) received N-acetylcysteine in the perioperative period, whereas the control group (37 patients) did not. The data obtained were analysed using the independent sample t-test (Student's t-test) and chi-test. RESULTS: There was no significant difference in the incidence of renal dysfunction between the two groups. Three patients (8.6%) in the N-acetylcysteine group and four (11.4%) in the control group developed renal dysfunction (P value was 1.00). CONCLUSION: N Acetylcysteine does not have any beneficial effect on renal function in high-risk patients undergoing off-pump coronary artery bypass graft. PMID- 20299985 TI - Cognitive and psychiatric disorder in myotonic dystrophy. PMID- 20299986 TI - Glottic web mimicking subglottic stenosis: revisited. PMID- 20299987 TI - Late intravascular migration of a previously well functioning labour epidural catheter. AB - Intravascular epidural catheters may result in insufficient labour analgesia or can produce potentially lethal complications following an epidural top-up. We report a case of a previously well functioning epidural catheter positioned epidurally using a combined spinal epidural anaesthesia technique, which subsequently was found to be intravascular. The literature is reviewed. PMID- 20299988 TI - Effects of a continuous low-dose clonidine epidural regimen on pain, satisfaction and adverse events during labour: a randomized, double-blind, placebo-controlled trial. AB - BACKGROUND AND OBJECTIVE: Epidural clonidine has been proposed as an adjunct for anaesthetic mixtures during labour. Administered as a bolus, clonidine may have side effects such as sedation and hypotension; its continuous infusion could be attractive in this respect. We, therefore, conducted a randomized, double-blind trial using patient-controlled epidural analgesia with a background infusion using a low dose of clonidine during labour. METHODS: A total of 128 healthy parturients in active labour received a patient-controlled epidural analgesia solution of 0.0625% levobupivacaine and sufentanil 0.25 microg ml(-1) with or without clonidine 2 microg ml(-1). Ninety-five parturients were analysed. The pain score over time was evaluated as well as drug volume utilization; supplementation bolus and side effects were recorded. The primary endpoint was maternal satisfaction [ClinicalTrials.gov Identifier (NCT00437996)]. RESULTS: Three patients in the control group failed to achieve satisfactory epidural analgesia owing to a technical issue. Although the primary endpoint was not statistically significant, analgesia was more pronounced and obtained earlier in the clonidine group. The area under the curve for the visual analogue pain score was significantly lower in the clonidine group. In this group, hourly doses of levobupivacaine and sufentanil were reduced (13.9 +/- 4.3 vs. 16.3 ml +/- 4.0; P = 0.005) as well as rescue supplementation and pruritus incidence (18 vs. 46%; P = 0.004). Maternal blood pressure was significantly lower, over time, in the clonidine group but remained within the normal range. Sedation was similar in both groups (4.3 vs. 2.0%; not significant). CONCLUSION: The addition of clonidine to epidural levobupivacaine and sufentanil for patient-controlled epidural analgesia in labour improved analgesia, reduced the supplementation rate and reduced pruritus without improvement in maternal satisfaction. Blood pressure was significantly lower in the clonidine group over time but without clinical consequence. PMID- 20299989 TI - Persistent pain following knee arthroplasty. AB - BACKGROUND AND OBJECTIVE: The prevalence of persistent pain after orthopaedic surgery has been the subject of only few studies and the risk factors for persistent pain have been evaluated even more rarely. The purpose of the present study was to evaluate the degree and the risk factors of persistent pain after knee arthroplasty. METHODS: The prevalence of persistent postoperative pain after knee replacement was evaluated with a questionnaire in a large, register-based cross-sectional prevalence study. The main hypothesis was that the type of operation (primary, bilateral, revision) would influence the prevalence of persistent postoperative pain. Logistic regression analysis was performed to test the hypothesis and to find other possible risk factors for the development of persistent pain. RESULTS: The total number of patients was 855. The operation was a primary arthroplasty in 648 patients (75.7%), a bilateral arthroplasty in 137 patients (21.1%) and a revision arthroplasty in 70 patients (8.2%). The response rate was 65.7%. The type of operation was not associated with the prevalence of persistent pain, but the degree of early postoperative pain was the strongest risk factor. If the degree of pain during the first postoperative week was from moderate to intolerable, the risk for the development of persistent pain was three to 10 times higher compared with patients complaining of mild pain during the same period. Other risk factors were the long duration of preoperative pain and female sex. CONCLUSION: Intensity of early postoperative pain and delayed surgery increase the risk of the persistent pain after knee arthroplasty. PMID- 20299990 TI - Bispectral index-controlled postoperative sedation in cardiac surgery patients: a comparative trial between closed loop and manual administration of propofol. AB - BACKGROUND AND OBJECTIVE: Postoperative cardiac surgery patients are usually sedated according to clinical sedation scores. Electrophysiological data derived from electroencephalography, such as the bispectral index (BIS), have been reported to assess and quantify the level of sedation, although experience in these patients is limited. In the current study, we evaluated a closed-loop system - closed-loop anaesthesia delivery system (CLADS) - for postoperative sedation after open heart surgery using BIS. METHODS: Forty-one postoperative cardiac surgery patients in the age group 18-65 years were included. In the postanaesthesia care unit, they were randomly allocated to two groups: a CLADS group, which received a continuous infusion of propofol using CLADS, and a manual group, which received propofol at a rate manually adjusted by the clinician. Propofol was administered in both groups to maintain the BIS at a target of 70 for adequate sedation. Patients were weaned from mechanical ventilation and the trachea extubated after confirmation of haemodynamic stability, haemostasis, normothermia and mental orientation. RESULTS: The percentage of total sedation time during which BIS remained within +/-10 of the target value (BIS of 70 during sedation) was significantly higher in the CLADS group than in the manual group (P = 0.002). The assessment of performance parameters using median performance error and median absolute performance error indicated better performance in the CLADS group. Manual control required the propofol infusion rate to be changed frequently, taking up considerable time and attention of the clinician. CONCLUSION: Closed-loop delivery of propofol to control BIS for postoperative sedation is feasible and efficient after cardiac surgery. PMID- 20299991 TI - Tourniquet use during total knee replacement in a Jehovah's Witness with sickle cell trait: a case report. PMID- 20299992 TI - Preoperative chronic pain in radical prostatectomy patients: preliminary evidence for enhanced susceptibility to surgically induced pain. AB - BACKGROUND AND OBJECTIVE: The aim of the study was to examine a possible relationship between the extent of preoperative chronic pain and the development of moderate-to-severe acute postoperative pain. METHODS: Eighty-four patients scheduled for radical prostatectomy were studied. Pain intensities after mobilization during the first 3 postoperative days were added to yield a total pain score (total pain score after mobilization, range 0-30). Pain was considered as moderate to severe at a total pain score after mobilization of 12 or higher. The preoperative severity of chronic pain disorders was measured using the Mainz Pain Staging System (I-III). Further possible preoperative risk factors for the development of intense postoperative pain that were examined included pain intensity, pain in the urological site, psychological distress (Hospital Anxiety and Depression Scale) and health-related quality of life (Short Form-12). RESULTS: Patients with moderate-to-severe preoperative chronic pain and those with higher Mainz Pain Staging System stages were significantly (P < 0.001) more likely to develop moderate-to-severe postoperative pain. Anxiety and depression scores as well as physical health (Short Form-12) were significantly associated with a total pain score after mobilization of at least 12. The development of postoperative pain was independent of the presence of preoperative pain in the urological site. CONCLUSION: This study demonstrated that higher degrees of preoperative chronic pain were associated with the development of more intense pain after radical prostatectomy. Preoperative psychological distress and reduced physical health were associated with a marked increase in postoperative pain intensity. PMID- 20299993 TI - An opioid-free anaesthetic using nerve blocks enhances rapid recovery after minor hand surgery in children. AB - BACKGROUND AND OBJECTIVE: The aim of this prospective randomized study was to evaluate the quality of analgesia, postoperative comfort and subsequent duration of hospitalization after distal hand surgery and peripheral nerve block at the wrist for paediatric outpatients. METHODS: Sixty consecutive ASA I or II children were randomly assigned to the following groups: in group B (block), intraoperative and postoperative analgesia was provided by peripheral nerve block; and in group O (opioids), intraoperative and postoperative analgesia was provided by intravenous opioids. The patients' age, sex and type of surgery were recorded as were the postoperative pain management and postoperative vomiting. Time to discharge from the recovery room, the postoperative ward and the time to discharge home were also noted. RESULTS: The two groups were similar with respect to age, sex, ASA physical status, weight, height and types of injuries. The incidence of postoperative pain (CHEOPS score >or=7) and the incidence of postoperative vomiting were significantly higher in group O than in group B: 26.6 versus 3.3%; P = 0.025, and 33.3 versus 6.6%; P = 0.011, respectively. The time before oral intake was significantly longer in group O than in group B [187 (75 265) min versus 60 (32-125) min, respectively, P = 0.0002]. The time to meet discharge home criteria was 277 (230-330) min in group O versus 210 (145-260) min in group B (P = 0.0039). CONCLUSION: The present study demonstrates for the first time that, after distal hand surgery in children, peripheral nerve block improves pain management, opioid analgesia-induced side effects and provides a shorter postoperative recovery time than systemic analgesia with opioids. PMID- 20299994 TI - Determinants of cerebral oximetry in patients undergoing off-pump coronary artery bypass grafting: an observational study. AB - BACKGROUND AND OBJECTIVE: The present study investigated whether positioning of the heart during off-pump coronary artery bypass grafting leads to changes in regional cerebral oxygen saturation measured by near infrared spectroscopy. METHODS: In 35 consecutive patients undergoing elective off-pump coronary artery bypass grafting, cerebral oxygen saturation was measured by near infrared spectroscopy. A 20% decrease from baseline values was considered to be cerebral hypoperfusion. Mean arterial pressure, cardiac index, arterial carbon dioxide partial pressure, central venous pressure, haemoglobin concentration, and body temperature were determined simultaneously. Each value was recorded at the following time points: at baseline; after positioning the heart for distal anastomoses of the left anterior descending artery, the circumflex, and the right coronary artery; after repositioning the heart; and after chest closure. Significant changes in each parameter from baseline were detected using repeated measures analysis of variance. Determinants of cerebral oxygen saturation during surgery were analysed by means of generalized estimation equations. RESULTS: Cerebral oxygen saturation remained constant during grafting of the left anterior descending artery and decreased significantly during grafting of the circumflex (P = 0.001) and the right coronary artery (P < 0.001). Cerebral hypoperfusion was found in seven (20%) patients. Changes in haemoglobin concentration (P = 0.014), arterial CO2 partial pressure (P = 0.001), cardiac output (P < 0.001), and central venous pressure (P = 0.014) determined alterations in cerebral oxygen saturation. CONCLUSION: Positioning of the heart during off-pump coronary artery bypass grafting leads to a decrease in regional cerebral oxygen saturation. This decrease is associated with changes in cardiac output, haemoglobin concentration, arterial CO2 partial pressure, and central venous pressure. PMID- 20299995 TI - Comfort of the patient during axillary blocks placement: a randomized comparison of the neurostimulation and the ultrasound guidance techniques. AB - BACKGROUND: Axillary brachial plexus block under neurostimulation is commonly used for upper limb surgery, but it is sometimes recognized as an uncomfortable technique, with most patients identifying electrical stimulation as an unpleasant moment. Ultrasound-guided regional anaesthesia, which becomes an increasingly popular technique, does not require electrical stimulation and then should theoretically improve axillary block placement comfort. The aim of this study was to compare the comfort of the patients during axillary block placement with neurostimulation and ultrasound guidance using either the out-of-plane or the in plane approach. METHODS: Consecutive patients were prospectively enrolled in three equal groups: neurostimulation, ultrasound out-of-plane and ultrasound in plane approaches. A score was used to measure the comfort of the patients during axillary blocks placement. This score included three criteria: maximum pain intensity perceived during block placement measured using a visual analogue scale (0, no pain and 100, maximal or worse imaginable pain), the number of unpleasant events declared by the patients and the satisfaction of the patient (unsatisfied, acceptable, satisfied, very satisfied). The comfort score was calculated as the sum of each criterion, which was attributed a value of 0 or 1: visual analogue scale (30/100, 0), number of unpleasant events (0, 1; >or=1, 0) and satisfaction (satisfied or very satisfied, 1; acceptable or unsatisfied, 0). Procedures of axillary blocks placement resulting in a comfort score of 3 and 2 were arbitrary considered as very comfortable and comfortable, respectively. Success rate of axillary blocks, time to perform block and complications related to procedures were noted. RESULTS: One hundred and twenty patients were included. In the ultrasound out-of-plane group, 55% (22/40) and 25% (10/40) of the procedures were very comfortable and comfortable as compared with 32% (13/40, P < 0.05) and 20% (8/40, P < 0.01) in the ultrasound in-plane group and 25% (10/40, P < 0.01) and 8% (3/40, P < 0.01) in the neurostimulation group, respectively. Duration of axillary placement was significantly smaller in the ultrasound out-of plane group as compared with that of in-plane approaches (P < 0.05) and neurostimulation (P < 0.01). CONCLUSION: The present study showed that the ultrasound approaches were less painful and more comfortable than neurostimulation to place axillary blocks. We also showed that, although pain intensity resulting from blocks placement was similar with the ultrasound approaches, very comfortable procedures were more frequent with the out-of-plane than with the in-plane approach. PMID- 20299996 TI - General anaesthesia for MRI in children with hypotonia: a case series. AB - BACKGROUND AND OBJECTIVE: To characterize the safety of general anaesthesia, used to facilitate MRI in children with clinical hypotonia, and to determine whether this technique could be performed safely as an outpatient procedure. METHODS: All children (age =30 kg/m2) prevalence increased from 14 to 24%, and no change in smoking behavior was observed. The prevalence of hyperlipidemia (total cholesterol >=4.5 mmol/l or low-density lipoprotein cholesterol >=2.5 mmol/l) at referral declined from 92% in 1996-1997 to 45% in 2006-2007. The proportion of patients with blood pressure above 140/90 mmHg decreased from 66 to 51%. The use of lipid-lowering, blood pressure-lowering, and antithrombotic medication at referral increased over the observation period. CONCLUSION: An improvement in risk factor profile was seen in patients referred with manifest vascular disease or DM2 over a 12-year period. Nevertheless, the prevalence of modifiable risk factors is still high leaving patients at elevated vascular risk. PMID- 20300001 TI - Cardiac rehabilitation in Europe: results from the European Cardiac Rehabilitation Inventory Survey. AB - BACKGROUND: Cardiac rehabilitation (CR) programmes support patients to achieve professionally recommended cardiovascular prevention targets and thus good clinical status and improved quality of life and prognosis. Information on CR service delivery in Europe is sketchy. DESIGN: Postal survey of national CR related organizations in European countries. METHODS: The European Cardiac Rehabilitation Inventory Survey assessed topics including national guidelines, legislation and funding mechanisms, phases of CR provided and characteristic of included patients. RESULTS: Responses were available for 28 of 39 (72%) countries; 61% had national CR associations; 57% national professional guidelines. Most countries (86%) had phase I (acute inhospital) CR, but with differing service availability. Only 29% reported provision to more than 80% patients. Phase II was also available, but 15 countries reported provision levels below 30%. Almost half (46%) had national legislation regarding phase II CR; three-quarters had government funding. Phase III was less supported: although available in most countries, 11 could not provide estimates of numbers participating. Thirteen reported that all costs were met by patients. CONCLUSION: Fewer than half of eligible cardiovascular patients benefit from CR in most European countries. Deficits include absent or inadequate legislation, funding, professional guidelines and information systems in many countries. Priorities for improvement include promoting national laws and guidelines specific for CR and increasing both CR programme participation rates and CR infrastructure. The European Association of Cardiovascular Prevention and Rehabilitation can have an important coordinating role in sharing expertise among national CR-related agencies. Ultimately, such cooperation can accelerate CR delivery to the benefit of cardiac patients across Europe. PMID- 20300002 TI - Obesity, physical activity and the development of metabolic syndrome: the Atherosclerosis Risk in Communities study. AB - BACKGROUND: The objective of this study is to determine the impact of body weight and physical activity on the development of metabolic syndrome (MetS). DESIGN AND METHODS: We used the public use data from the Atherosclerosis Risk in Communities study. From the baseline cohort, we identified, as the study population, 9359 individuals who did not have MetS and who completed the second follow-up examination in 1993-1995. RESULTS: In 6 years of follow-up, 1970 individuals (25%) developed MetS. Compared with normal weight group [body mass index (BMI)<25 kg/m], the odds ratios [95% confidence interval (CI)] of incident MetS were 2.81 (95% CI: 2.50-3.17) and 5.24 (95% CI: 4.50-6.12) for the overweight (BMI: 25-30 kg/m) and the obese groups (BMI>or=30 kg/m), respectively. Compared with persons in the lowest quartile of leisure-time physical activity, the odds ratios (95% CI) of incident MetS were 0.80 (95% CI: 0.71-0.91) and 0.92 (95% CI: 0.81-1.04) for persons in the highest and the middle quartiles of leisure-time physical activity, respectively. Our results indicated that at any level of physical activity, there is a graded increase in the risk of incident MetS with an increase in BMI, in contrast to a lack of graded association between physical activity and the incidence of MetS in all categories of BMI. CONCLUSION: This study highlights the need to target obesity more than physical activity in preventing the development of MetS. PMID- 20300003 TI - Improving documentation of procedural sedation in an adult emergency department. AB - INTRODUCTION: This study evaluates the effects of an educational intervention and the use of a preprinted form on the adequacy of documentation of procedural sedation in an adult emergency department. METHODS: The study was conducted at a tertiary hospital's emergency department. Structured medical record review was performed before and after a multipronged educational intervention and again after the introduction of a preprinted form that included factors distilled from published procedural sedation guidelines. Good documentation was defined as having less than five of 22 documentation items missing, and greater than 10 items missing was defined as a poor documentation. RESULTS: The baseline group consisted of 93 patients with 102 included posteducation and 118 included after the introduction of the form. At baseline, 4.3% had good documentation, and 47.3% had poor documentation. Posteducation, these results were 16.7 and 30.4% for good and poor documentation, respectively. After the introduction of the form, 33.9% had good documentation and 38.1% had poor documentation. Only 39% of cases used the form, which resulted in 80.4% of medical records having good documentation and with none having poor documentation. Concurrently, if the form was not used to assist documentation, 1.4% had good documentation and 62.5% had poor documentation. CONCLUSION: Baseline documentation was poor and improved slightly after both the educational interventions. Use of a preprinted form was associated with no medical records being classified as having poor documentation; however, uptake of the form use was low. Emergency departments should develop and consider mandatory use of such an aid together with training staff in the use of the aid and the important implications of adequate procedural documentation. PMID- 20300004 TI - Tolerance and outcome of patients with unresectable hepatocellular carcinoma treated with sorafenib. AB - BACKGROUND: Sorafenib is the standard treatment for patients with an advanced stage of hepatocellular carcinoma (HCC). The aims of this study were (i) to evaluate the tolerance and survival of sorafenib-treated patients, in a nonselected population, especially in Child-Pugh B patients; and (ii) to identify potential prognostic factors of survival. PATIENTS AND METHODS: From April 2007 to December 2008, 50 patients received sorafenib for advanced HCC. Seventeen (34%) were Child-Pugh B patients. We recorded adverse events and the duration of treatment and survival. For 34 patients with histopathologically proven HCC, immunophenotypical analysis was carried out using antibodies against cluster differentiation 34, vascular endothelial growth factor, phosphorylated ERK, cytokeratin 19, and phosphorylated stat3. RESULTS: Patients with Child-Pugh B cirrhosis had a more advanced stage of the disease compared with Child-Pugh A patients. The occurrence of adverse events was similar in Child-Pugh A and Child Pugh B patients. Duration of treatment until discontinuation for bad tolerance was lower in Child-Pugh B patients (1.8 vs. 5 months, P=0.02). Survival of Child Pugh A patients was higher compared with Child-Pugh B patients (8.9 vs. 2 months, P=0.004). Barcelona Clinic Liver Cancer stage, Eastern Cooperative Oncology Group Performance Status, portal vein impairment, extra-hepatic spread, and alpha foetoprotein were also prognostic factors. In multivariate analysis, the sole factor associated with survival was the Barcelona Clinic Liver Cancer stage. None of the immunohistological markers used was associated with tolerance and survival. CONCLUSION: Occurrence of adverse events is similar in Child-Pugh A and Child-Pugh B patients. Nevertheless, the survival of Child-Pugh B patients is very low. Whether liver function or tumor spread is responsible for mortality is unclear. Opportunity of treatment for Child-Pugh B patients is questionable. The immunophenotype of tumoral tissue was not predictive of survival. PMID- 20300005 TI - Kupffer cell depletion reduces hepatic inflammation and apoptosis but decreases survival in abdominal sepsis. AB - OBJECTIVE: During abdominal sepsis, the activation of hepatic Kupffer cells (KC) and its consequences are of central interest. This study evaluates the impact of selective KC depletion on hepatic microcirculation, cytokine release, and systemic alterations in the colon ascendens stent peritonitis (CASP), a model of polymicrobial abdominal sepsis. METHODS: For KC depletion clodronate liposomes were injected 24 h before CASP surgery in female C57BL/6N mice. Three and 12 h after CASP, in-vivo fluorescence microscopy of the liver was performed. Analysis of hepatocellular apoptosis was conducted by immunohistochemistry. In addition, levels of tumor necrosis factor (TNF), IL-6, and IL-10 in the liver, lungs, spleen, and plasma were determined, and bacteriology and survival analysis were performed. RESULTS: CASP led to significant sinusoidal perfusion failure, increased leukocyte recruitment, hepatocellular apoptosis and increased levels of TNF, IL-6, and IL-10 in the liver and plasma. KC depletion before CASP significantly reduced leukocyte recruitment to the liver and hepatocellular apoptosis. IL-10 secretion decreased dramatically in the liver and plasma of KC depleted septic mice. In contrast, TNF levels were clearly elevated after clodronate treatment. In the lung and spleen, a compensatory upregulation of IL 10 could be detected after KC depletion. Clodronate treatment resulted in a significant reduction in survival. CONCLUSION: The results indicate that KC depletion is locally protective in polymicrobial abdominal sepsis, as it reduces hepatic inflammation and apoptosis. These effects could be observed in the presence of clearly elevated TNF levels. However, the lack of IL-10 in KC depleted mice resulted in a detrimental systemic proinflammation. PMID- 20300006 TI - Appropriate diagnosis of biliary cystic tumors: comparison with atypical hepatic simple cysts. AB - BACKGROUND: Biliary cystadenoma (BCA) and biliary cystadenocarcinoma (BCAC) are often confused with other intrahepatic cystic diseases. AIMS: The aims of this study were to investigate predictive factors of biliary cystic tumor (BCT) and clinical characteristic of BCAC. METHODS: We retrospectively reviewed preoperative diagnoses, overall characteristics and postoperative outcome of 20 BCTs and 19 cystadenoma-mimicking simple cysts that were pathologically confirmed. RESULTS: Comparing with atypical simple cysts, symptoms, left-lobe cyst, thick wall, septation, mural nodule, bile duct dilatation and an increase of serum alkaline phosphatase were associated with BCTs. However, on multivariate analysis, mural nodule, left-lobe cyst, and an increase of serum alkaline phosphatase were significantly frequent in BCTs with odds ratios of 75.5, 13.8, and 33.0, respectively. Among the 20 BCTs, seven BCACs were diagnosed. The characteristics of BCACs were mural nodule (P<0.01), intrahepatic cyst debris (P<0.01), and bile duct dilation (P=0.04). Cystic fluid analysis provided no significant differences between BCT and simple cyst. After fine needle aspiration cytology of BCTs, all except one BCAC with atypical cell showed nonspecific findings. After complete surgical excision (97.4% of patients), only one patient with BCAC had recurrence during 29 months of follow-up period. CONCLUSION: In hepatic cysts with mural nodule, left-lobe cyst or increment of serum alkaline phosphatase seem to be indicative of BCTs in the diagnosis of suspicious hepatic cyst. Intracystic debris, bile duct dilation, and mural nodule may be suggestive clinical features of malignancy in BCTs. PMID- 20300007 TI - The histone deacetylase inhibitor ITF2357 decreases surface CXCR4 and CCR5 expression on CD4(+) T-cells and monocytes and is superior to valproic acid for latent HIV-1 expression in vitro. AB - OBJECTIVES: Chromatin-associated repression is one mechanism that maintains HIV-1 latency. Inhibition of histone deacetylases (HDAC) reverses this repression resulting in viral expression from quiescently infected cells. Clinical studies with the HDAC inhibitor valproic acid (VPA) failed to substantially decrease the latent pool within resting CD4(+) cells. Here we compared the efficacy of ITF2357, an orally active and safe HDAC inhibitor, with VPA for HIV-1 expression from latently infected cells in vitro. We also evaluated the effect of ITF2357 on the surface expression of CXCR4 and CCR5. METHODS: Latently infected cell lines were incubated with either ITF2357 or VPA and p24 levels were measured. Peripheral blood mononuclear cells of uninfected donors were treated with ITF2357 and HIV-1 coreceptors expression was assessed by flow cytometry. RESULTS: At clinically relevant concentrations, ITF2357 increased p24 by 15-fold in ACH2 cells and by 9-fold in U1 cells, whereas VPA increased expression less than 2 fold. Analogues of ITF2357 primarily targeting HDAC-1 increased p24 up to 30 fold. In CD4(+) T cells treated with ITF2357, CXCR4 expression decreased by 54% (P < 0.001). CONCLUSION: ITF2357 is superior to VPA in inducing HIV-1 from latently infected cells. Safely used in humans, ITF2357 is an attractive candidate for HIV-1 clinical purging. PMID- 20300008 TI - Evolution of integrase resistance during failure of integrase inhibitor-based antiretroviral therapy. AB - BACKGROUND: Although integrase inhibitors are highly effective in the management of drug-resistant HIV, some patients fail to achieve durable viral suppression. The long-term consequences of integrase inhibitor failure have not been well defined. METHODS: We identified 29 individuals who exhibited evidence of incomplete viral suppression on a regimen containing an integrase inhibitor (23 raltegravir, 6 elvitegravir). Before initiating the integrase inhibitor-based regimen, the median CD4 T-cell count and plasma HIV RNA levels were 62 cells/mm and 4.65 log10 copies/mL, respectively. RESULTS: At the first failure time-point, the most common integrase resistance pattern for subjects taking raltegravir was wild-type, followed in order of frequency by Q148H/K/R+G140S, N155H, and Y143R/H/C. The most common resistance pattern for subjects taking elvitegravir was E92Q. Long-term failure was associated with continued viral evolution, emergence of high-level phenotypic resistance, and a decrease in replicative capacity. CONCLUSIONS: Although wild-type failure during early integrase inhibitor failure is common, most patients eventually develop high-level phenotypic drug resistance. This resistance evolution is gradual and associated with declines in replicative capacity. PMID- 20300009 TI - MRI restricted diffusion in optic nerve infarction after autologous fat transplantation. AB - A 24-year-old woman reported blindness in the left eye upon awakening from fat autotransplantation to her forehead for soft tissue augmentation in the face. Clinical findings on the third postoperative day suggested ipsilateral ophthalmic artery occlusion with infarction of the optic nerve and retina. There were also clinical manifestations of a mild right hemiparesis. MRI diffusion-weighted imaging (DWI) revealed restricted diffusion of the left optic nerve and left middle cerebral artery domain indicative of the cytotoxic edema of infarction. This is the second report of optic nerve infarction after fat autotransplantation to the forehead and the first report of DWI restricted diffusion in this setting. PMID- 20300010 TI - Elbow septic arthritis in children: clinical presentation and management. AB - The elbow is a rare location for septic arthritis, and this fact may produce diagnostic errors. The purpose of this study is to determine the most typical clinical presentation and to evaluate the management and functional outcome of these patients. We present our experience with this entity. This is a retrospective study of seven cases between February 2004 and November 2007, five girls and two boys with a mean age of 2.8 years, ranging from 1.2 to 4.9 years. We explain our diagnosis criteria and management algorithm. Functional results were evaluated using the Mayo Elbow Performance Score. It is necessary to suspect septic arthritis in an elbow with persistent pain and functional limitation (24 48 h) and no earlier trauma. The most frequent infectious agent is Staphylococcus aureus. Using specific antibiotics until the disappearance of radiological changes we have obtained excellent clinical results according to the Mayo Elbow Performance Score. PMID- 20300011 TI - The relation of triceps surae surgical lengthening and crouch gait in patients with cerebral palsy. AB - To investigate the effect of earlier triceps surae (TS) surgical lengthening at knee kinematics in the stance phase in patients with cerebral palsy (CP). One thousand and thirty-nine participants from an eligible total of 1750 children with CP were referred to gait analysis laboratory from January 2000 to April 2007. Inclusion criteria were the diagnosis of diparetic spastic CP levels I to III (GMFCS) and complete kinematics documentation. Patients with an asymmetrical knee pattern at kinematics and with different types of TS management among sides were excluded. The patients were divided into two groups according to the mean minimum knee flexion (MMKF) in stance phase: group A (n=253) MMKF > or =30 degrees and group B (n=786) MMKF less than 30 degrees . For each group, the occurrence of following procedures for TS in the past: (i) earlier surgery, (ii) gastrocnemius lengthening (zone I), (iii) gastrocnemius and soleus lengthening (zone II), and (iv) calcaneous tendon lengthening (zone III), was investigated. A chi test was applied to check if the number of procedures performed was different between groups. The level of significance was defined as P value of less than 0.05. The number of patients with no earlier surgeries at TS was higher in group B (51.8%) than in group A (39.1%), and this difference was significant (P<0.01). In addition, the number of procedures at the calcaneous tendon was more elevated in group A (36.8%) than in group B (27%), and this finding was statistically significant as well (P<0.02). The percentage of surgical lengthening at zones I and II was very similar between the groups A and B. This study has shown that patients without earlier surgical procedures at TS are more susceptible to reach better extension of the knees in the stance phase. Patients in a crouch gait had a higher number of calcaneous tendon lengthening performed in the past than patients with a more normal knee extension in the stance phase. PMID- 20300012 TI - Single vs. multiple sets of resistance exercise for muscle hypertrophy: a meta analysis. AB - Previous meta-analyses have compared the effects of single to multiple sets on strength, but analyses on muscle hypertrophy are lacking. The purpose of this study was to use multilevel meta-regression to compare the effects of single and multiple sets per exercise on muscle hypertrophy. The analysis comprised 55 effect sizes (ESs), nested within 19 treatment groups and 8 studies. Multiple sets were associated with a larger ES than a single set (difference = 0.10 +/- 0.04; confidence interval [CI]: 0.02, 0.19; p = 0.016). In a dose-response model, there was a trend for 2-3 sets per exercise to be associated with a greater ES than 1 set (difference = 0.09 +/- 0.05; CI: -0.02, 0.20; p = 0.09), and a trend for 4-6 sets per exercise to be associated with a greater ES than 1 set (difference = 0.20 +/- 0.11; CI: -0.04, 0.43; p = 0.096). Both of these trends were significant when considering permutation test p values (p < 0.01). There was no significant difference between 2-3 sets per exercise and 4-6 sets per exercise (difference = 0.10 +/- 0.10; CI: -0.09, 0.30; p = 0.29). There was a tendency for increasing ESs for an increasing number of sets (0.24 for 1 set, 0.34 for 2-3 sets, and 0.44 for 4-6 sets). Sensitivity analysis revealed no highly influential studies that affected the magnitude of the observed differences, but one study did slightly influence the level of significance and CI width. No evidence of publication bias was observed. In conclusion, multiple sets are associated with 40% greater hypertrophy-related ESs than 1 set, in both trained and untrained subjects. PMID- 20300013 TI - Vertical jump performance and blood ammonia and lactate levels during typical training sessions in elite 400-m runners. AB - This study described the effects of 6 typical high-intensity intermittent running training sessions of varying distances (60-300 m) and intensities (80-105% of the individual best 400-m record time) on blood ammonia and lactate concentration changes and on vertical jumping height, in twelve 400-m elite male runners. At the end of the training sessions, similar patterns of extremely high blood lactate (14-23 mmol.L) and ammonia levels (50-100 mumol.L) were observed. Vertical jumping performance was maintained during the initial exercise bouts up to a break zone of further increase in the number of exercise bouts, which was associated, especially in subjects with the highest initial vertical jump, with a pronounced decrease (6-28%) in vertical jumping performance, as well as with blood lactate concentrations exceeding 8-12 mmol.L, and blood ammonia levels increasing abruptly from rest values. This break zone may be related to signs of energetic deficiency of the muscle contractile machinery associated with the ability to regenerate adenosine triphosphate at high rates. It is suggested that replacing some of these extremely demanding training sessions with other intermittent training sessions that preserve muscle generating capacity should allow elite athletes to practice more frequently at competitive intensity with lower fatigue. PMID- 20300014 TI - Amino acid supplements and recovery from high-intensity resistance training. AB - The purpose of this study was to investigate whether short-term amino acid supplementation could maintain a short-term net anabolic hormonal profile and decrease muscle cell damage during a period of high-intensity resistance training (overreaching), thereby enhancing recovery and decreasing the risk of injury and illness. Eight previously resistance trained males were randomly assigned to either a high branched chain amino acids (BCAA) or placebo group. Subjects consumed the supplement for 3 weeks before commencing a fourth week of supplementation with concomitant high-intensity total-body resistance training (overreaching) (3 x 6-8 repetitions maximum, 8 exercises). Blood was drawn prior to and after supplementation, then again after 2 and 4 days of training. Serum was analyzed for testosterone, cortisol, and creatine kinase. Serum testosterone levels were significantly higher (p < 0.001), and cortisol and creatine kinase levels were significantly lower (p < 0.001, and p = 0.004, respectively) in the BCAA group during and following resistance training. These findings suggest that short-term amino acid supplementation, which is high in BCAA, may produce a net anabolic hormonal profile while attenuating training-induced increases in muscle tissue damage. Athletes' nutrient intake, which periodically increases amino acid intake to reflect the increased need for recovery during periods of overreaching, may increase subsequent competitive performance while decreasing the risk of injury or illness. PMID- 20300015 TI - Nutritional supplementation, performance, and oxidative stress in college soccer players. AB - The purpose of this study was to examine changes in performance and metabolic parameters in collegiate soccer players during preseason preparation and to determine the impact of a nutraceutical blend proposed to reduce oxidative stress. Male Division I college soccer players (n = 22) performed a progressive maximal treadmill test at the beginning and end of preseason to assess changes in Vo2max, velocity at lactate threshold (VLT), time-to-exhaustion, lipid hydroperoxide (LPO), 8-isoprostane, and creatine kinase (CK) response. After baseline testing, athletes were randomly assigned to receive the nutraceutical blend (EXP; n = 12) or an isocaloric equivalent (CON; n = 10) for 20 days of preseason training. DeltaVo2max (2.1 +/- 3.3 ml.kg.min, p = 0.007), DeltaVLT (0.8 +/- 1.4 km.h, p = 0.045), and Deltatime-to-exhaustion (39.4 +/- 77.4 seconds, p = 0.033) were improved across groups, but a significant effect of supplementation on performance was not seen. Changes in resting levels of CK from the beginning to end of preseason were significantly lower (p = 0.044) in EXP (64.8 +/- 188.4 U.L) than in CON (292.8 +/- 304.8 U.L). Additionally, EXP demonstrated a significant decrease in the magnitude of the 8-isoprostane response at Trial 2 compared with Trial 1 (effect size [ES] = -0.74), whereas CON had an increased response (ES = 0.20). A similar pattern was seen for LPO (p = 0.067). Preseason training in male college soccer players resulted in significant improvements in Vo2max, VLT, and time-to-exhaustion. Supplementing with a proprietary antioxidant and nutraceutical blend may enhance some of these effects as indicated by magnitude of the responses. However, it appears that the most notable effects of supplementation were seen for reduced CK and oxidative stress, at least with short-term supplementation. PMID- 20300016 TI - Arginine and ornithine supplementation increases growth hormone and insulin-like growth factor-1 serum levels after heavy-resistance exercise in strength-trained athletes. AB - This placebo-controlled double-blind study was designed to investigate the effect of arginine and ornithine (arg and orn) supplementation during 3-week heavy resistance training on serum growth hormone/insulin-like growth factor-1/insulin like growth factor-binding protein 3 (GH/IGF-1/IGFBP-3), testosterone, cortisol, and insulin levels in experienced strength-trained athletes. The subjects were randomly divided between a placebo group (n = 8) and the l-Arg/l-Orn-supplemented group (n = 9), and performed pre and posttraining standard exercise tests with the same absolute load, which consisted of the same exercise schedule as that applied in the training process. Fasting blood samples were obtained at rest, 2 minutes after the cessation of the strength exercise protocol, and after 1 hour of recovery. The resting concentrations of the investigated hormones and IGFBP-3 did not differ significantly between the study groups. In response to exercise test, all the hormones were elevated (p < 0.05) at both time points. Significant increases (p < 0.05) were observed in both GH and IGF-1 serum levels after arg and orn supplementation at both time points, whereas a significant decrease was seen in IGFBP-3 protein during the recovery period. Because there was no between group difference in the remaining hormone levels, it appears that the GH/IGF 1/IGFBP-3 complex may be the major player in muscle tissue response to short-term resistance training after arg and orn supplementation. PMID- 20300017 TI - Anabolic and catabolic hormones and energy balance of the male bodybuilders during the preparation for the competition. AB - The purpose of the study was to investigate simultaneous effects of energy balance, caloric intake, and the hormonal anabolic-catabolic balance in bodybuilders prior to competition. Fourteen male bodybuilders took part in an 11 week energy-restricted period to reduce body fat. The subjects were divided into the energy-restricted group (ERG) (n = 7), who were preparing for the competition, or the control group (CG) (n = 7) who continued to train regularly and did not change their dietary or training pattern. Participants were tested at 11 weeks (T1), 5 weeks (T2), and 3 days (T3) before competition for diet, body composition, and fasting hormonal assessment. Body mass and body fat percentage of ERG were significantly (p < 0.05) decreased during the study period. In ERG, insulinlike growth factor-1 (IGF-1) and insulin decreased significantly during the 11-week weight-reduction period (p < 0.05). Testosterone was decreased only from week 11 to week 5 (from 20.3 +/- 6.0 to 18.0 +/- 6.8 nmol/L). Changes in IGF I concentration were significantly related to changes in insulin (r = 0.741), fat mass (r = 0.705), lean body mass (r = 0.696), and body mass (r = 0.652). Changes in insulin concentrations were significantly related to changes in fat mass (r = 0.630) and lean body mass (r = 0.725). These data indicate that severe energy restriction to extremely low body energy reserves decreases significantly the concentrations of 3 anabolic pathways despite high protein intake. Monitoring of insulin and IGF-1 concentration is suggested to prevent losses in muscle mass in energy-restricted conditions. Other nutritional strategies might be needed to prevent possible catabolic effect during preparation of bodybuilders to competition. PMID- 20300018 TI - Selected factors correlated to athletic performance in adults with mental retardation. AB - The aims of this study were to assess the contribution of selected factors to the athletic performance in adults with mental retardation (MR) and to analyze the correlation of each factor with subjects' MR levels. Twenty-nine trained athletes with MR aged 20-45 years were recruited. The fundamental factors included anthropometric measurements, flexibility, muscular strength and endurance, explosive leg power, cardiovascular endurance, and motor coordination. The athletic performances were as follows: 60 m, 300 m, 400 m in walking, standing long jump, and vortex throw (Level I) or 100-m run, shot put, and long jump (Level II). Motor coordination and body weight had significant contributions to 60 m (p < 0.01) and the %body fat had significant contribution to 300 m and 100 m (p < 0.05). The explosive leg power had significant contribution to vortex throw and standing long jump (p < 0.05). The upper-body strength and muscular endurance had significant contribution in shot put (p < 0.05). The body weight had significant contribution in long jump (p < 0.05). MR level was positively correlated to motor coordination (p < 0.05) and negatively to abdominal muscular strength and endurance (p < 0.05). In conclusion, the results showed the possibility to determine the contributions of selected factors to the athletic performance. This should be addressed in athletics training to help athletes with MR to perform successfully in their competitions. PMID- 20300019 TI - The effect of a traditional dance training program on the physical fitness of adults with hearing loss. AB - The purpose of this study was to evaluate the effect of a traditional dance training program on aerobic capacity and muscle strength of adults with hearing loss. Twenty-three adults with hearing loss were separated into 2 groups. Thirteen subjects (6 men, 7 women, mean age, 25.7 +/- 3.9 years) constituted the intervention group, whereas 10 subjects (5 men, 5 women, mean age, 26.4 +/- 5.9 years) formed the control group. Pretraining and posttraining treadmill tests were performed to determine heart rate (HR peak), peak minute ventilation (VE peak), peak oxygen consumption (VO2 peak, absolute and relative), and time to exhaustion (min). Peak torque of hamstring and quadriceps muscles at angular velocities of 60 degrees /s, 180 degrees /s, and 300 degrees /s was also measured. The intervention group followed a 12-week traditional dance training program, whereas the control group received no training during this period. Repeated measures of multiple analyses of variance were used to test mean differences between the values of both groups. A paired t-test was used to compare the values within each group prior and after program participation. A significance level of 0.05 was used for all tests. Following the 12-week training program, significant improvements in peak physiological parameters were seen for the intervention group for peak minute ventilation, peak oxygen consumption (both absolute and relative), time to exhaustion, and peak torque values between the 2 measurements (initial and final). No significant improvements in peak physiological parameters and peak torque were noticed in the control group. In conclusion, adults with hearing loss can improve their physical fitness levels with the application of a systematic and well-designed traditional dance training program. PMID- 20300020 TI - The metabolic costs of reciprocal supersets vs. traditional resistance exercise in young recreationally active adults. AB - An acute bout of traditional resistance training (TRAD) increases energy expenditure (EE) both during exercise and in the postexercise period. Reciprocal supersets (SUPERs) are a method of resistance training that alternates multiple sets of high-intensity agonist-antagonist muscle groups with limited recovery. The purpose of this study was to compare the energy cost of SUPERs and TRAD both during and in the postexercise period. We hypothesized that SUPERs would produce greater exercise EE relative to the duration of exercise time and greater excess postexercise oxygen consumption (EPOC) than TRAD of matched work. Ten recreationally active, young men each participated in 2 exercise protocols: SUPER, followed 1 week later by TRAD matched within using a 10-repetition maximum load for 6 exercises, 4 sets, and repetitions. Participants were measured for oxygen consumption and blood lactate concentration during exercise and 60 minutes postexercise after each exercise bout. No significant differences were observed in aerobic exercise EE between trials (SUPER 1,009.99 +/- 71.42 kJ; TRAD 954.49 +/- 83.31 kJ); however, when expressed relative to time, the exercise EE was significantly greater during SUPER (34.70 +/- 2.97 kJ.min) than TRAD (26.28 +/- 2.43 kJ.min). Excess postexercise oxygen consumption was significantly greater after SUPER (79.36 +/- 7.49 kJ) over TRAD (59.67 +/- 8.37 kJ). Average blood lactate measures were significantly greater during SUPER (5.1 +/- 0.9 mmol.L) than during TRAD (3.8 +/- 0.6 mmol.L). Reciprocal supersets produced greater exercise kJ.min, blood lactate, and EPOC than did TRAD. Incorporating this method of resistance exercise may benefit exercisers attempting to increase EE and have a fixed exercise volume with limited exercise time available. PMID- 20300021 TI - Effects of quadriceps and hamstrings proprioceptive neuromuscular facilitation stretching on knee movement sensation. AB - Stretching before competition has traditionally been thought to benefit performance; however, recent evidence demonstrating reduced muscle force and power immediately after stretching suggests otherwise. We hypothesized that knee joint position sense would be diminished immediately after proprioceptive neuromuscular facilitation (PNF) stretching to the hamstrings and quadriceps. Eighteen subjects (aged 18-30 years) were seated with their dominant foot attached to a motorized arm with the knee flexed at 135 degrees . To block external cues, the subjects wore a blindfold, earplugs, and headphones providing white noise. The knee was displaced in either the flexion or the extension direction at a velocity of 0.4 degrees .s, and subjects pressed a button when they sensed motion. The knee was returned to 135 degrees , and the test was repeated for a total of 10 trials. The PNF group received PNF stretching to the hamstrings and quadriceps of the dominant leg. The SHAM group had the dominant leg passively moved within each subject's functional range of motion. The ability to detect knee movement was retested in the PNF and SHAM groups. Pre- and posttest latencies between movement onset and subject response were analyzed. Results indicated that the PNF group had significantly increased latencies after stretching (from 2.56 +/- 0.83 to 3.46 +/- 1.90 seconds) compared with the SHAM group (3.93 +/- 2.40 to 3.72 +/- 2.15 seconds). It is concluded that PNF stretching of the hamstrings and quadriceps may acutely diminish sensitivity to knee movement. For coaches and trainers, these findings are consistent with previous reports of loss in muscle force and power immediately after stretching, suggesting that stretching just before competition may diminish performance. PMID- 20300022 TI - Oxygen cost of kettlebell swings. AB - In recent years, kettlebells have re-emerged as a popular training modality for the conditioning of athletes. We sought to quantify the aerobic challenge of one popularly recommended kettlebell workout. Ten college-aged men (age = 20.8 +/- 1.1 years, height = 179 +/- 3 cm, body mass = 77.3 +/- 7.7 kg, Vo2max = 52.78 +/- 6.22 ml.kg.min) completed a graded exercise test to exhaustion for the determination of Vo2max. Two to 7 days later, subjects completed a kettlebell exercise routine consisting of as many 2-handed swings as could be completed in 12 minutes using a 16-kg kettlebell. During this exercise bout, subjects' expired gases were collected and analyzed for the determination of Vo2, and heart rate (HR) was continuously measured. Percent HRmax and Vo2max achieved during the kettlebell exercise were compared with each other using a paired t-test. Subjects completed 265 +/- 68 swings during the 12 minutes and achieved an average Vo2 of 34.31 +/- 5.67 ml.kg.min and an average HR of 165 +/- 13 b.min. The average %HRmax (86.8 +/- 6.0%) during kettlebell exercise was significantly higher (p < 0.001) than the average Vo2max (65.3 +/- 9.8%) that was achieved. Continuous kettlebell swings can impart a metabolic challenge of sufficient intensity to increase Vo2max. Heart rate was substantially higher than Vo2 during kettlebell swings. Kettlebells provide a useful tool with which coaches may improve the cardiorespiratory fitness of their athletes. However, HRs achieved during continuous kettlebell exercise are significantly higher than actual Vo2. PMID- 20300023 TI - Muscle activation when performing the chest press and shoulder press on a stable bench vs. a Swiss ball. AB - The aim of this study was to examine the effects of a stable surface (bench) vs. an unstable surface (Swiss ball) on muscle activation when performing the dumbbell chest press and shoulder press. Sixteen healthy men (24.19 +/- 2.17 years) performed 1 repetition maximum (1RM) tests for the chest press and shoulder press on a stable surface. A minimum of 48 hours post 1RM, subjects returned to perform 3 consecutive repetitions each of the chest press and shoulder press at 80% 1RM under 4 different randomized conditions (chest press on bench, chest press on Swiss ball, shoulder press on bench, shoulder press on Swiss ball). Electromyography was used to assess muscle activation of the anterior deltoid, pectoralis major, and rectus abdominus. The results revealed no significant difference in muscle activation between surface types for either exercise. This suggests that using an unstable surface neither improves nor impairs muscle activation under the current conditions. Coaches and other practitioners can expect similar muscle activation when using a Swiss ball vs. a bench. PMID- 20300025 TI - Hamstring muscle extensibility influences the criterion-related validity of sit and-reach and toe-touch tests. AB - The aim of this study was to analyze the influence of hamstring muscle extensibility on the hamstring criterion-related validity of the sit-and-reach (SR) and toe-touch (TT) tests. Two hundred forty young adults (mean age: 22.9 +/- 3.6 years) participated in this study. Three trials of straight leg raise (SLR) (left and right), SR, and TT tests were performed in a random order. The subjects were dichotomized into group A (subjects with an SLR angle < 75 degrees ) or group B (subjects with an SLR angle >/= 75 degrees ). The correlation values between SLR angle and SR and TT scores were calculated and compared between both groups. Group B elicited higher mean SR and TT scores than group A (p < 0.001). Group A showed low associations between SLR with respect to the SR (r = 0.31 0.41) and TT (r = 0.28-0.40) tests. Group B showed moderate values for both SR (r = 0.55) and TT (r = 0.60-0.61) tests. The hamstring criterion-related validity of the SR and TT tests is influenced by hamstring muscle extensibility. From the results of this investigation, we find that the SR and TT tests are not valid measures of hamstring extensibility for subjects with reduced hamstring muscle extensibility. PMID- 20300024 TI - Fatigue effects on knee joint stability during two jump tasks in women. AB - Dynamic knee joint stability may be affected by the onset of metabolic fatigue during sports participation that could increase the risk for knee injury. The purpose of this investigation was to determine the effects of metabolic fatigue on knee muscle activation, peak knee joint angles, and peak knee internal moments in young women during 2 jumping tasks. Fifteen women (mean age: 24.6 +/- 2.6 years) participated in one nonfatigued session and one fatigued session. During both sessions, peak knee landing flexion and valgus joint angles, peak knee extension and varus/valgus internal moments, electromyographic (EMG) muscle activity of the quadriceps and hamstrings, and quadriceps/hamstring EMG cocontraction ratio were measured. The tasks consisted of a single-legged drop jump from a 40-cm box and a 20-cm, up-down, repeated hop task. The fatigued session included a Wingate anaerobic protocol followed by performance of the 2 tasks. Although participants exhibited greater knee injury-predisposing factors during the fatigued session, such as lesser knee flexion joint angles, greater knee valgus joint angles, and greater varus/valgus internal joint moments for both tasks, only knee flexion during the up-down task was statistically significant (p = 0.028). Metabolic fatigue may perhaps predispose young women to knee injuries by impairing dynamic knee joint stability. Training strength endurance components and the ability to maintain control of body movements in either rested or fatigued situations might help reduce injuries in young women athletes. PMID- 20300026 TI - The physical and anthropometric profiles of adolescent alpine skiers and their relationship with sporting rank. AB - The aim of this work was to determine the somatotype of national-level adolescent Spanish skiers, to establish the maximum strength and anaerobic power of their legs, and to examine the relationship between these variables and their national ranks. The study subjects were 31 adolescents skiers, of whom 15 were girls and 16 boys; all were 13-16 years old. Their percentage body fat and muscular mass were recorded, as was their ability to jump (countermovement jump [CMJ]), the strength and power of their legs (squat test), and their anaerobic power (Wingate and continuous jump [CMJ30''] tests). The mesomorphic somatotype was the most common among the boys, whereas the endomesomorphic somatotype was the most common among the girls. In the boys, sporting rank was significantly correlated with muscular mass (rs = 0.70; p = 0.003), with the CMJ and CMJ30'' (rs = 0.67; p < 0.01, and rs = 0.59; p < 0.05, respectively), and with the mean power and maximum dynamic strength in the squat test (rs = 0.59; p = 0.017). No such relationships were seen for the girls. None of the Wingate test variables, except for mean power (in the boys only; rs = 0.55; p < 0.05), correlated with sporting rank. The results suggest that power, as measured by the CMJ and CMJ30'', and the strength and power of the legs, as measured by the squat test, are associated with the sporting success of male skiers but not of female skiers. Power, as measured by the Wingate test, cannot be used to predict the performance of either sex. PMID- 20300027 TI - Whole-body vibration training effects on the physical performance of basketball players. AB - The aim of this study was to investigate the influence of 4 weeks of whole-body vibration training added to the conventional training of basketball players. Eighteen competitive basketball players (13 male symbol, 5 female symbol, 18-24 years old) were randomly assigned to a whole-body vibration group (WBVG, n = 10; 7 male symbol and 3 female symbol) or a control group (CG, n = 8; 6 male symbol and 2 female symbol). During the 4-week period, all subjects maintained their conventional basketball training program. The members of WBVG were additionally trained 3 times a week for 20 minutes on a vibration platform (10 unloaded static lower limb exercises, 40-Hz, 4-mm, Silverplate). Testing was performed before and after the 4-week period and comprised strength assessment, vertical jump performance, and a 10-m sprint test. The maximal voluntary isometric strength of the knee extensors significantly increased (p < 0.001) after vibration training, as did squat jump (SJ) height (p < 0.05), whereas performance of the countermovement jump, drop jump, 30-second rebound jump, and 10-m sprint remained unchanged. The results of the present study indicated that a 4-week whole-body vibration training program added to the conventional training of basketball players during the preseason is an effective short-term stimulus to enhance knee extensor strength and slightly SJ performance. PMID- 20300028 TI - Effect of a prior force-velocity test performed with legs on subsequent peak power output measured with arms or vice versa. AB - The aim of this study was to examine whether measurement of peak anaerobic power (Wpeak) by force-velocity test using the arms or the legs influenced the performance obtained when the opposite muscle group was tested. Ten trained male throwers (age: 20.6 +/- 2; stature: 1.82 +/- 0.06 m; and body mass: 85.5 +/- 17.2 kg) performed, on separate days, 2 Monark cycle-ergometer protocols comprising (a) arm cranking (A1) followed by a leg cycling (L2) force-velocity test (series A-L) and (b) a leg cycling (L1) followed by an arm cranking (A2) force-velocity test (series L-A). On each day, 8 minutes of seated rest separated the 2 force velocity tests. Arterialized capillary blood was collected from the finger tips for blood lactate analysis at rest and at the end of each force-velocity test. Wpeak-A1 and Wpeak-A2 were similar (8.1 +/- 1.7 and 8.6 +/- 1.5 W.kg, respectively). Wpeak-L1 and Wpeak-L2 were 14.0 +/- 3 and 13.4 +/- 2.8 W.kg (NS). Blood [La] increased significantly after each force-velocity test (p < 0.001), but peak blood [La] did not differ significantly between L1 (6.6 +/- 1.2) and L2 (6.2 +/- 1.4 mmol.L) or between A1 (7.2 +/- 1.0) and A2 (7.4 +/- 1.6 mmol.L). In this population, force-velocity tests performed using the legs or the arms did not induce a significant decrease in force-velocity determinations of peak anaerobic power performed subsequently with the opposite muscle group. In strength-trained athletes, the force-velocity approach can thus be used to measure the peak power output of both the legs and the arms in a single laboratory session, without adversely affecting estimates of an athlete's performance. PMID- 20300029 TI - Two days of hypoxic exposure increased ventilation without affecting performance. AB - The aim of this study was to test the short-term effects of using hypoxic rooms before a simulated running event. Thirteen subjects (29 +/- 4 years) lived in a hypoxic dormitory (1,800 m) for either 2 nights (n = 6) or 2 days + nights (n = 7) before performing a 1,500-m treadmill test. Performance, expired gases, and muscle electrical activity were recorded and compared with a control session performed 1 week before or after the altitude session (random order). Arterial blood samples were collected before and after altitude exposure. Arterial pH and hemoglobin concentration increased (p < 0.05) and PCO2 decreased (p < 0.05) upon exiting the room. However, these parameters returned (p < 0.05) to basal levels within a few hours. During exercise, mean ventilation (VE) was higher (p < 0.05) after 2 nights or days + nights of moderate altitude exposure (113.0 +/- 27.2 L.min) than in the control run (108.6 +/- 27.8 L.min), without any modification in performance (360 +/- 45 vs. 360 +/- 42 seconds, respectively) or muscle electrical activity. This elevated VE during the run after the hypoxic exposure was probably because of the subsistence effects of the hypoxic ventilatory response. However, from a practical point of view, although the use of a normobaric simulating altitude chamber exposure induced some hematological adaptations, these disappeared within a few hours and failed to provide any benefit during the subsequent 1,500-m run. PMID- 20300030 TI - Comparison of active, manual, and instrumental straight leg raise in measuring hamstring extensibility. AB - The active manual straight leg raise (ASLR) and passive manual straight leg raise (MSLR) tests are commonly used in clinical settings to assess hamstring tightness. However, to our knowledge, the validity and sensitivity of these tests have not been compared with the instrumental straight leg raise (ISLR). The aim of the present study was to assess the intrarater reproducibility of the ISLR and compare the sensitivity of the ASLR, MSLR, and ISLR to change. Twelve men with hamstring tightness underwent the ASLR, MSLR, and ISLR tests at baseline and after a 4-week home-based right leg stretching program with the left leg serving as a control. The ISLR measurements were repeated consecutively at baseline to assess reproducibility. The intraclass correlation coefficient for the ISLR was 0.94, and the coefficient of reproducibility was 6. Significant differences in the range of motion emerged between all testing methods (p < 0.05). In the stretched legs, the mean +/- SD increases were 17 +/- 5 degrees for ISLR, 10 +/- 8 degrees for ASLR, and 6 +/- 5 degrees for MSLR, whereas the control legs showed a significant mean change only for ASLR (5 +/- 4 degrees ). The mean standard response with the ASLR and MSLR tests did not differentiate between the treated and control legs, but it was almost 10-fold higher in the treated leg than the control leg for the ISLR, clearly differentiating between them. The ISLR had good reproducibility and sensitivity to changes, whereas ASLR and MSLR showed a poor ability to detect changes. Thus, the ISLR test is recommended for use in research evaluating the effectiveness of stretching. PMID- 20300031 TI - Lower extremity muscle activation during baseball pitching. AB - The purpose of this study was to investigate muscle activation levels of select lower extremity muscles during the pitching motion. Bilateral surface electromyography data on 5 lower extremity muscles (biceps femoris, rectus femoris, gluteus maximus, vastus medialis, and gastrocnemius) were collected on 11 highly skilled baseball pitchers and compared with individual maximal voluntary isometric contraction (MVIC) data. The pitching motion was divided into 4 distinct phases: phase 1, initiation of pitching motion to maximum stride leg knee height; phase 2, maximum stride leg knee height to stride foot contact (SFC); phase 3, SFC to ball release; and phase 4, ball release to 0.5 seconds after ball release (follow-through). Results indicated that trail leg musculature elicited moderate to high activity levels during phases 2 and 3 (38-172% of MVIC). Muscle activity levels of the stride leg were moderate to high during phases 2-4 (23-170% of MVIC). These data indicate a high demand for lower extremity strength and endurance. Specifically, coaches should incorporate unilateral and bilateral lower extremity exercises for strength improvement or maintenance and to facilitate dynamic stabilization of the lower extremities during the pitching motion. PMID- 20300032 TI - Gender influence on response time to sensory stimuli. AB - The purpose of this investigation was to examine the effect of auditory stimuli (AS) and visual stimuli (VS) on response time, speed, and distance in male and female college athletes. Thirty-five healthy National Collegiate Athletic Association Division I men's soccer and women's lacrosse athletes (mean age 20.7 +/- 2.3 years) participated in the study. This experiment was conducted in a laboratory environment, using a Cybex "Reactor" a 14-sensor force plate device used to detect response times, speed, and distance. Subjects stood on the "start" sensor and were instructed at the prompt (auditory: a prerecorded "go" command, visual: an illuminated circle on a television monitor) to run through the "end" sensor without braking. Three trials of each condition were performed by each subject. Movement time, speed, and distance were recorded for each trial. General linear model repeated measure analyses and post hoc 1-way analysis of variance were conducted on all dependent variables (p < or = 0.05). Movement time was significantly faster in men compared with women under AS (p = 0.008) and VS (p < 0.05) conditions. A trend toward a faster transit time was noted in men in the AS condition (p = 0.072), but transit time was faster in men in the VS condition (p < 0.001). Transit speed (distance covered) was faster in men in response to AS (p < 0.05) and VS (p < 0.001). Male athletes respond faster as compared with female athletes, and cover greater distance when presented with VSs as compared to ASs. Data suggest that performance in male athletes related to response times, speed, and distance may be enhanced with the use of visual cueing or VSs. PMID- 20300033 TI - Acute effects of different warm-up methods on sprint, slalom dribbling, and penalty kick performance in soccer players. AB - Although pre-event static stretching is an accepted practice in most athletics program, pre-event dynamic exercise is becoming popular. The purpose of this study was to compare the acute effects of different warm-up methods on soccer performance. Twenty-six professional soccer players (23.3 +/- 3.2 years, 178.2 +/ 6.1 cm, and 73.0 +/- 6.5 kg) performed 4 different warm-up routines in random order on nonconsecutive days. The warm-up methods consisted of only 5 minutes of jogging (Method A), 5 minutes of jogging and static stretching (Method B), 5 minutes of jogging and dynamic exercise (Method C), and 5 minutes of jogging and a combination of static stretching and dynamic exercise (Method D). After each warm-up session, subjects were tested on the sprint, slalom dribbling, and penalty kick performance. Methods A-D were compared by repeated-measures analyses of variance and post hoc comparisons. In this study, existence of a significant drop in sprint, slalom dribbling, and penalty kick performances of Method C has been determined in comparison with that of Method A (p < 0.05). Again for sprint, slalom dribbling, and penalty kick performances of Method A in comparison with those of Method A, the existence of a significant increase has been determined (p < 0.05). In Method D in comparison with Method A, for sprint, slalom dribbling, and penalty kick performances, existence of no significant difference has been determined (p > 0.05). The results of this study suggest that it may be desirable for soccer players to perform dynamic exercises before the performance of activities that require a high power output. PMID- 20300034 TI - Physiological responses and characteristics of table tennis matches determined in official tournaments. AB - The purpose of this study was to verify the physiological responses and the match characteristics of table tennis and also to compare these responses in 2 different performance-level athletes from official tournaments. Twenty male table tennis players (12 regional experience-RP and 8 national and international experience-NP) were participants in the study. Blood lactate concentration ([LAC]) and heart rate (HR) were measured as physiological parameters in 21 official table tennis matches, and other 12 matches had recorded the duration of rally (DR), rest time, effort and rest ratio (E:R), total playing time (TPT), effective playing time (EPT), and frequency of shots by video analyses. The [LAC] verified in all matches was 1.8 mmol.L (+/-0.8), whereas the [LAC] peak was 2.2 mmol.L (+/-0.8). There were no significant differences between the 2 groups (p > 0.05) in both parameters. The HR was 164 b.min (+/-14), corresponding to 81.2% (+/-7.4) of the predicted maximum HR. As characteristics of the matches, the DR corresponded to 3.4 seconds (+/-1.7), rest time to 8.1 seconds (+/-5.1), E:R to 0.4 (+/-0.2), TPT to 970.5 seconds (+/-336.1), EPT to 44.3% (+/-23.7), and frequency of shots to 35.3 balls.min (+/-7.7). Among groups, the rest time was lower in RP than in NP. Consistently, the E:R and EPT were higher in RP than in NP (p < 0.05). The results suggest that table tennis matches present the aerobic system as a principal output energy, the phosphagenic system being the most important during efforts. The information pertaining to the physiological profile and the characteristics of table tennis should be used by coaches planning physical training and specific exercise prescriptions aiming at achieving maximal sport performance. PMID- 20300035 TI - Short-term effects of complex and contrast training in soccer players' vertical jump, sprint, and agility abilities. AB - The purpose of this study was to analyze the short-term effects of complex and contrast training (CCT) on vertical jump (squat and countermovement jump), sprint (5 and 15 m), and agility (505 Agility Test) abilities in soccer players. Twenty three young elite Portuguese soccer players (age 17.4 +/- 0.6 years) were divided into 2 experimental groups (G1, n = 9, and G2, n = 8) and 1 control group (G3, n = 6). Groups G1 and G2 have done their regular soccer training along with a 6 week strength training program of CCT, with 1 and 2 training sessions.wk, respectively. G3 has been kept to their regular soccer training program. Each training session from the CCT program was organized in 3 stations in which a general exercise, a multiform exercise, and a specific exercise were performed. The load was increased by 5% from 1 repetition maximum each 2 weeks. Obtained results allowed identifying (a) a reduction in sprint times over 5 and 15 m (9.2 and 6.2% for G1 and 7.0 and 3.1%, for G2; p < 0.05) and () an increase on squat and jump (12.6% for G1 and 9.6% for G2; p < 0.05). The results suggested that the CCT induced the performance increase in 5 and 15 m sprint and in squat jump. Vertical jump and sprint performances after CCT program were not influenced by the number of CCT sessions per week (1 or 2 sessions.wk). From the obtained results, it was suggested that the CCT is an adequate training strategy to develop soccer players' muscle power and speed. PMID- 20300036 TI - Two series of fifty jumps performed within sixty minutes do not exacerbate muscle fatigue and muscle damage. AB - Previous studies have demonstrated that an exercise bout repeated prior to full recovery, within 2-6 days, does not impair muscle function to a greater extent and does not affect the repair process. The aim of this study was to examine whether repeated exercise performed 60 minutes after the first one exacerbates muscle fatigue and damage. Ten healthy, physically active males (21.1 +/- 1.4 years, 75.2 +/- 4.1 kg, 178.7 +/- 4.5 cm) performed 2 bouts of 50 continuous maximal intensity jumps with a 60-minute rest period. Peak quadriceps muscle force evoked by electrical stimulation at 15 (P15) and 50 (P50) Hz and maximal voluntary contraction force (MVCF) were measured 2, 30, and 60 minutes after bout 1 and bout 2. The results demonstrated a significant decrease in P15, P50, and MVCF during bout 1 (p < 0.05). The force did not recover within 60 minutes after exercising. After the second bout, the MVCF and P50 decreased to similar extent both immediately after and 30-60 minutes after the first one despite the fact that bout 2 was repeated with the voluntary and involuntary force still depressed. It was concluded that within 60 minutes repeated jumping exercise does not exacerbate muscle fatigue and muscle damage. From the coach's point of view it is of significance that the neuromuscular system appears to be well protected from frequently repeated muscle damaging exercise. PMID- 20300038 TI - Relationship between strength, power, speed, and change of direction performance of female softball players. AB - The purpose of this study was to investigate (a) the cross-sectional relationship of strength, power, and performance variables in trained female athletes and (b) determine if the relationship between these variables changes over the course of a season. Ten female softball players (age = 18.1 +/- 1.6 years, height = 166.5 +/- 8.9 cm, and weight = 72.4 +/- 10.8 kg) from a state Australian Institute of Sport softball team were tested for maximal lower body strength (one repetition maximum [1RM]), peak force (PF), peak velocity (PV), and peak power (PP) during jump squats unloaded and loaded, unloaded countermovement vertical jump height (VJH) 1 base and 2 base sprint performance and change of direction performance on dominant and nondominant sides. The testing sessions occurred pre, mid, and post a 20-week training period. Relationship between body weight (BW), relative strength (1RM/BW), VJH, relative PP, relative PF, PV, speed, and change of direction variables were assessed by Pearson product-moment correlation coefficient at each testing session. Significant relationships were found across all time points with BW, speed, and change of direction measures (r = 0.70-0.93) and relative strength and measures of speed and change of direction ability (r = 0.73-0.85). There were no significant relationships between VJH and any measure of performance at any time point. In conclusion, BW and relative strength have strong to very strong correlations with speed and change of direction ability, and these correlations remain consistent over the course of the season. However, it seems as if many relationships vary with time, and their relationships should therefore be investigated longitudinally to better determine if these cross sectional relationships truly reflect a deterministic relationship. PMID- 20300037 TI - Elite female soccer players perform more high-intensity running when playing in international games compared with domestic league games. AB - The purpose of this study was to compare movement pattern, fatigue development, and heart rate (HR) for top-class elite female players when playing international (INT) vs. domestic league games (DOM). Video-based time-motion analyses and HR recordings were performed on 17 players during INT and DOM. The distances covered in high-intensity running (HIR) and sprinting were longer (p < 0.05) in INT compared with DOM. More (p < 0.05) HIR was covered in INT than DOM during first and second half. Additionally, more (p < 0.05) sprinting occurred in INT compared with DOM in the first half. In both game types, the amount of HIR was reduced by 24-27% (p < 0.05) in the last 15-minute period compared with the first four 15 minute periods of the game. The midfielders covered longer (p < 0.05) distances with HIR in INT than in DOM over the entire game and in the most intense 5-minute period of the games, whereas no differences were observed between the game types for defenders. No difference in the HR response was found between INT and DOM. In conclusion, more HIR and sprinting occur in international compared with domestic games, which may affect the fatigue development for players in physically demanding roles. Thus, our results are important to coaches to prepare players to meet the challenges of international soccer games and show that the ability to perform intense intermittent exercise should be trained regularly in elite female players. PMID- 20300039 TI - Sensitization of human melanoma cells by tamoxifen to apoptosis induction by pancratistatin, a nongenotoxic natural compound. AB - The objective of this study was to determine the efficacy of the natural compound pancratistatin (PST), isolated from the Hymenocallis littoralis, in human melanoma cells. Melanoma is an aggressive form of skin cancer that is commonly fatal if not diagnosed in its early stage of development. Melanoma is resistant to many treatments, thus drastically limiting chemotherapy options for this cancer. We have shown that exposure to PST induces apoptosis in human melanoma within 72 h using Hoechst staining. Interestingly tamoxifen (TAM), an estrogen receptor antagonist, sensitizes these cells to apoptosis induction by PST as observed with Hoechst and annexin-V staining. This cotreatment did not affect the viability of normal noncancerous human fibroblasts. Both of these compounds have been shown to target the mitochondria synergistically, as indicated by higher levels of reactive oxygen species generation from isolated mitochondria. PST alone and in combination with TAM shows depolarization of the mitochondrial membrane potential as shown by JC-1 staining. Melanoma drug resistance was not observed after posttreatment recuperation, as cells displayed apoptotic morphology up to 96 h after drug-free media replacement. Our results indicate that TAM alone does not induce apoptosis in this cell line, but sensitizes the mitochondria, thereby enhancing the effect of PST exposure. In conclusion, combination of two nongenotoxic compounds offers a novel treatment regime for this notoriously resilient form of skin cancer. PMID- 20300041 TI - Electroencephalographic dynamics of musical emotion perception revealed by independent spectral components. AB - This study explores the electroencephalographic (EEG) correlates of emotional experience during music listening. Independent component analysis and analysis of variance were used to separate statistically independent spectral changes of the EEG in response to music-induced emotional processes. An independent brain process with equivalent dipole located in the fronto-central region exhibited distinct delta-band and theta-band power changes associated with self-reported emotional states. Specifically, the emotional valence was associated with delta power decreases and theta-power increases in the frontal-central area, whereas the emotional arousal was accompanied by increases in both delta and theta powers. The resultant emotion-related component activations that were less interfered by the activities from other brain processes complement previous EEG studies of emotion perception to music. PMID- 20300042 TI - Role of FDG-PET/CT in detection of recurrent disease in colorectal cancer. AB - BACKGROUND: One-third of patients with colorectal cancer (CRC) are likely to have a recurrence within the first 1-2 years. Conventional imaging modalities have limitations in detecting recurrent disease early. The purpose of this study was to assess the usefulness of fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) in the detection of recurrence in patients with CRCs. METHODS: One hundred and eighty-three patients, who were earlier treated with surgery and/or chemotherapy/radiotherapy, underwent 269 PET/CT studies for the detection of recurrence. The final diagnosis was made on the basis of histological analysis or clinical and imaging follow-up. RESULTS: The sensitivity, specificity, accuracy, positive predictive value, and negative predictive value in detecting recurrent CRC using F-FDG-PET/CT were 87, 90, 88, 93, and 80%, respectively. PET/CT was found to have limitations in detecting microscopic disease and small-sized lesions. The common cause of false-positive PET/CT results was infective and inflammatory pathology in our setup. CONCLUSION: PET/CT showed high sensitivity, specificity, and accuracy for the detection of recurrent disease in patients, who were earlier treated for CRC. PET/CT can be considered as a useful diagnostic tool in these patients. PMID- 20300040 TI - Early menopausal hormone use influences brain regions used for visual working memory. AB - OBJECTIVE: The cognitive benefit of postmenopausal hormone use is controversial; however, timing of treatment close to menopause may increase the likelihood of preserving cognitive function. We examined the effects of early-initiation hormone use on visual working memory, hypothesizing that long-term hormone use is associated with greater brain activation during visual working memory. METHODS: This was a cross-sectional comparison of long-term early hormone users-current (n = 13) and past (n = 24; 2.1 +/- 1.0 years off hormones)-with never users (n = 18), using a visual memory task and functional magnetic resonance imaging (MRI). We evaluated 55 women older than 60 years at the University of Michigan's General Clinical Research Center. Hormone users had completed at least 10 continuous years of conjugated equine estrogens with or without medroxyprogesterone acetate, begun within 2 years of menopause. Women were excluded for illness, medication, intermittent estrogen use, phytoestrogen use, recent smoking, and MRI contraindications. The primary outcome was functional MRI-detected brain activity during the visual memory task. RESULTS: Compared with never users, both groups of hormone users had increased activation in the frontal and parietal cortices, insula, hippocampus, and cingulate; combined hormone users also had increased activation in the putamen and raphe (corrected P < 0.05 or uncorrected P < 0.001 with a priori hypothesis). Across the entire sample, the medial temporal cortex (P < 0.0001 right; P < 0.018 left) and right hippocampus (P < 0.0001) positively correlated with task performance. CONCLUSIONS: Hormone use was associated with increased brain activation during the visual memory task, in regions used for visual working memory. A positive correlation between activation and task performance suggests that early-initiation, long-term postmenopausal hormone use may benefit visual working memory. PMID- 20300043 TI - Comparison between short-acquisition myocardial perfusion SPECT reconstructed with a new algorithm and conventional acquisition with filtered backprojection processing. AB - OBJECTIVE: To compare a novel reconstruction package (Evolution for Cardiac), used to improve image quality in myocardial perfusion single photon emission computed tomography (MPS) and enable shorter scan acquisitions, to filtered backprojection used for conventional time acquisitions. METHODS: Forty-four patients who underwent 2-day Tc-99m sestamibi MPS had both standard [SD: 14-min scan and filtered backprojection processing] and short (SH: 6-min scan and iterative reconstruction with Evolution for Cardiac) studies. In a 17-segment model of the left ventricle, each segment was automatically scored 0-4 (normal to absent radiotracer activity); summed stress, rest and difference scores (SSS, SRS, SDS) were obtained. Spearman's test assessed the correlation between scores from SD and SH studies, and Bland-Altman plots evaluated absolute and mean differences of scores between these studies. RESULTS: The SSS, SRS, and SDS were not statistically different between SD and SH studies (SSS: 5.9 + or - 6.6 vs. 5.8 + or - 6.5; SRS: 2.6 + or - 3.5 vs. 2.6 + or - 2.9; SDS: 3.3 + or - 5.8 vs. 3.2 + or - 5.7). Significant correlations were observed between SD and SH studies regarding SSS (R(2)=0.93), SRS (R(2)=0.85), and SDS (R(2)=0.9) (all P<0.001). Bland-Altman plots showed that differences in SSS, SRS, and SDS fell within 2 standard deviations of the average differences between SD and SH studies. Overall agreement between clinical readings of SD and SH scans was good (up to 100% in abnormal scans). CONCLUSION: A new reconstruction package (Evolution for Cardiac) enabled short MPS acquisition without changes in quantitative perfusion results when compared with conventional acquisition and processing. PMID- 20300044 TI - Radiation therapy for the treatment of vestibular schwannoma: a critical evaluation of the state of the literature. AB - OBJECTIVE: Review publications reporting radiation treatment of vestibular schwannomas (VS) and describe how data, patient characteristics, and study endpoints were reported. DATA SOURCES: PubMed search for English language articles on radiation treatment of VS published from January 2002 to July 2007. STUDY SELECTION: Studies presenting outcomes were selected, yielding 56 articles (58 studies) in journals of neurosurgery (30), oncology (18), otolaryngology (6), and other (2). DATA EXTRACTION/SYNTHESIS: Data included type of study, number of subjects, demographics, follow-up times, type of radiation, tumor size, tumor control definition, control rates, facial nerve function measure and outcome, type of hearing and vestibular testing and outcomes, and complications. Descriptive statistics were performed. RESULTS: Studies (72.9%) were retrospective reviews with stated sample sizes ranging from 5 to 829. Gamma-knife (49.2%), linear accelerator (35.6%), and proton beam (6.8%) were used with various doses. Average follow-up was less than 5 years in 79.6% of studies, and 67.4% included patients at less than or equal to 1 year. Tumor size was reported as diameter (23.7%), volume (49.2%), both (11.9%), other (3.4%), or not reported (11.9%). Definition of tumor control varied: less than or equal to 2 mm growth (22.0%), no visible/measurable change (16.9%), required surgery (10.2%), other (17.0%), and not clearly specified (33.9%). Facial nerve outcome was reported as House-Brackmann (64.4%), normal/abnormal (11.9%), other (1.7%), or was not reported (22%). CONCLUSION: The lack of uniform reporting criteria for tumor control, facial function and hearing preservation, and variability in follow-up times make it difficult to compare studies of radiation treatment for VS. We recommend consideration of reporting guidelines such as those used in otology for reporting VS resection results. PMID- 20300045 TI - Trends in hospitalizations from all-cause gastroenteritis in children younger than 5 years of age in Brazil before and after human rotavirus vaccine introduction, 1998-2007. AB - Rotavirus vaccination was introduced in Brazil in March 2006. We describe trends in hospitalizations from all-cause gastroenteritis in children younger than 5 years during pre- and postvaccination periods using hospital discharge data from Brazil Hospital Information System (SIH-SUS). A reduction in gastroenteritis hospitalizations of 26% and 48% in 2006 and in 2007, respectively, was observed among children younger than 1 year compared with prevaccination period (1998 2005). The largest reduction rates among children younger than 1 year were noted in the South and Southeast regions, approximately 56% in 2007, where vaccine coverage was the highest. PMID- 20300046 TI - Impact of immigration on pulmonary tuberculosis in spanish children. PMID- 20300047 TI - COC use, ACE/AGT gene polymorphisms, and risk of stroke. AB - OBJECTIVES: To clarify the effects of the association between combined oral contraceptives (COC) use and ACE/AGT gene on stroke risk, and to undertake a preliminarily study of the molecular mechanism of the association between COC exposure and predisposing genes of hypertension on the increased risk of stroke. METHODS: This study was a multi-center case-control study based on the population of 25 towns in the surveillance regions of Jiangsu province, China. RESULTS: (i) The univariate analysis of the frequency of the DD genotype of ACE insert/delete (I/D) polymorphism between the cases and controls indicated its significant association with the stroke (P<0.01), especially for hemorrhagic stroke (P<0.01). (ii) Women with COC exposure and ACE I/D genotype had an increased risk for all strokes [adjusted odds ratio 5.63; 95% confidence interval (CI), 2.20, 15.68], and an increased risk for hemorrhagic stroke (adjusted odds ratio 31.53; 95% CI, 3.54, 281.14) after adjustment for education and occupation. (iii) Multivariate analyses showed that hypertension was the most important risk factor for hemorrhagic stroke and ischemic stroke. COC use was a significant risk factor for hemorrhagic stroke. The combined effects of COC use, for 15 years and above, and ACE I/D polymorphism increased the risk of all strokes by more than eight times, and the risk of hemorrhagic stroke by more than 15 times. CONCLUSION: Hypertension was a most important risk factor for stroke incidence. The D allele of ACE I/D polymorphism may be a potential risk allele for stroke. COC users carried the ID+DD genotype that may further increase the risk of stroke, especially for hemorrhagic stroke. PMID- 20300048 TI - Common genetic variation of beta1- and beta2-adrenergic receptor and response to four classes of antihypertensive treatment. AB - Varying results have been reported on the association of beta-adrenergic receptor polymorphisms with blood pressure (BP) response to beta-blockers. We investigated the influence of ADRB1 Ser49Gly and Arg389Gly, and ADRB2 Gly16Arg and Glu27Gln polymorphisms on ambulatory BP response to bisoprolol and three other antihypertensive drug monotherapies in a placebo-controlled, double-blind, cross over study with 233 moderately hypertensive men. ADRB1 Ser49Ser homozygotes tended to have a better ambulatory BP response to bisoprolol but the difference was statistically nonsignificant. ADRB1 Arg389Arg homozygotes did not show better BP response to bisoprolol than the other genotypes. There were no significant associations of ADRB2 polymorphisms with BP responses to any of the study drugs. The results from this controlled study in hypertensive men do not support clinical use of common polymorphisms in ADRB1 and ADRB2 in predicting BP responses to beta-blockers or to three other antihypertensive drugs. PMID- 20300049 TI - Polymorphisms spanning the TNFR2 and TACE genes do not contribute towards variable anti-TNF treatment response. AB - The introduction of tumour necrosis factor antagonists (anti-TNF) has greatly improved the treatment of rheumatoid arthritis, however, a significant proportion of patients fail to respond to therapy. We hypothesized that variants spanning the type 2 TNF receptor (TNFR2) and the TNF cleavage enzyme (TACE) genes contribute towards the observed variation in patient response (defined as the absolute change in 28-joint count disease activity score). Twenty-nine single nucleotide polymorphisms (SNPs) were genotyped in a large cohort of patients (n=602) and analysed by multivariate linear regression. Three SNPs (rs520916, rs652625, rs597519) mapping upstream of TNFR2 showed borderline evidence for association (P<0.1) across the complete cohort and, more so, in the etanercept treated subgroup. However, the evidence of association was neither replicated in an independent cohort (n=377) nor strengthened after combined analysis (n=979). We conclude that common SNPs spanning the TNFR2 and TNF cleavage enzyme (TACE) genes do not have a major effect on the response to anti-TNF therapy in rheumatoid arthritis patients. PMID- 20300050 TI - Determination of linezolid in human plasma by high-performance liquid chromatography with ultraviolet detection. AB - A high-performance liquid chromatographic method for the determination of linezolid in human plasma was developed and validated. After precipitation of plasma proteins with perchloric acid, the protein-free supernatant was separated by isocratic reverse-phase chromatography on a X Bridge C18 column. The mobile phase consisted of a mixture of phosphoric acid 0.05%: acetonitrile (75:25, v/v) with a flow rate of 1 mL/min. The column elute was monitored at 254 nm. The method was linear from 0.2 to 48 mg/L (mean r2 = 0.9996, n = 10). The observed intra- and inter-day assay imprecision ranged from 2.83% to 8.16% (18.80% at the lower limit of quantification); inaccuracy varied between -0.33% and 8.18%. Mean drug recovery was 99.8% for linezolid and 90.0% for the internal standard (para toluic acid). The method was found to be precise and accurate and suitable for therapeutic drug monitoring of linezolid in routine clinical practice. PMID- 20300051 TI - Successful human islet isolation and transplantation indicating the importance of class 1 collagenase and collagen degradation activity assay. AB - BACKGROUND: Purified tissue dissociation enzymes (TDEs) are critical to successful human islet isolation required for clinical transplantation, but little is known about the characteristics of the key enzymes-class I (C1) and class II (C2) collagenase from Clostridium histolyticum-used in these procedures. Here, we show the differences between the C1 collagenase found in purified collagenase products manufactured by three suppliers and the impact of differences in C1 between two suppliers on human islet yield. METHODS: Collagenase from Roche, Serva/Nordmark (Uetersen, Germany), and VitaCyte (Indianapolis, IN) were analyzed by analytical high-performance liquid chromatography and collagen degradation activity (CDA), an assay that preferentially detects intact C1 collagenase. Human islet isolations were performed using current standard practices. RESULTS: These studies showed that the highest amount of intact C1 that correlated with a high specific CDA (CDA unit per milligram of protein). The highest specific CDA was found in VitaCyte product followed by the Roche and Serva/Nordmark products. The products of VitaCyte were used successfully for human islet isolation (n=14) with an average final islet yield obtained was 419,100+/-150,900 islet equivalent number (IEQ) (4147+/-1759 IEQ/g pancreas). Four of these preparations were used successfully in clinical transplantation procedures. These TDEs gave significantly better results when compared with earlier data where 27 isolations were performed using Serva NB1 collagenase and NB neutral protease where the final islet yield was 217,500+/-152,400 IEQ (2134+/-1524 IEQ/g pancreas). CONCLUSIONS: These data indicate the importance of intact C1 and the use of the appropriate analytical assays to correlate biochemical characteristics of TDEs to islet quality and yield. PMID- 20300052 TI - Primary prevention of ulcers in patients taking aspirin or NSAIDs. AB - Aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) are common causes of peptic ulcer disease. Patients infected with Helicobacter pylori who take aspirin or another NSAID have an especially high risk. Drugs that have been tried for prevention of ulcers in patients taking NSAIDs including H2-receptor antagonists, proton pump inhibitors (PPIs), aluminum- or magnesium-containing antacids, the prostaglandin misoprostol (Cytotec, and others), and antibiotics to eradicate H. pylori. PMID- 20300053 TI - Rosiglitazone (Avandia) revisited. PMID- 20300054 TI - Hyperbaric oxygen therapy for refractory wounds. PMID- 20300055 TI - Decrease in reported tuberculosis cases - United States, 2009. AB - Every year, CDC reports results from the National TB Surveillance System for the previous year. For 2009, a total of 11,540 tuberculosis (TB) cases were reported in the United States. The TB rate was 3.8 cases per 100,000 population, a decrease of 11.4% from the rate of 4.2 per 100,000 reported for 2008. The 2009 rate showed the greatest single-year decrease ever recorded and was the lowest recorded rate since national TB surveillance began in 1953. TB case counts and rates decreased substantially among both foreign-born and U.S.-born persons, although foreign-born persons and racial/ethnic minorities continued to have TB disease disproportionate to their respective populations. The TB rate in foreign born persons was nearly 11 times higher than in U.S.-born persons. The rates among Hispanics and blacks were approximately eight times higher than among non Hispanic whites, and rates among Asians were nearly 26 times higher. The large decrease in reported cases during 2009 might represent a decrease in TB disease resulting from changes in population demographics or improved TB control. However, increased underreporting or underdiagnosis of TB also is possible. CDC currently is investigating possible causes for the sharp decrease in reported TB cases. Diagnosing and reporting all TB cases is essential to ensure treatment of patients with TB and implementation of other public health interventions that interrupt transmission. PMID- 20300056 TI - Monitoring tuberculosis programs - National Tuberculosis Indicator Project, United States, 2002-2008. AB - The National Tuberculosis Indicators Project (NTIP) is a secure, web-based monitoring system that uses routinely collected surveillance data on individual tuberculosis (TB) cases to measure the performance of state and local TB control programs, help programs to prioritize improvement efforts and focus on key TB control activities, and track progress toward national program objectives. Data are reported on a yearly basis and with frequent updates. This report summarizes NTIP results from the most recent 5 years for which data are available. Program performance was mixed, with general improvement for indicators related to TB case management (e.g., recommended initial therapy, genotyping data reported, human immunodeficiency virus [HIV] status reported, sputum culture reporting, and culture conversion documentation), but lower performance for indicators related to contact investigations of patients with infectious TB (e.g., contact elicitation, medical evaluation of contacts to infectious TB patients, and treatment initiation rate for persons diagnosed with latent TB infection [LTBI]). All performance indicators remained below the national performance targets for 2015. Starting in 2010, programs receiving CDC cooperative agreement funds for TB prevention and control will be required to use NTIP indicator data to describe their performance and formulate plans for improvement. PMID- 20300057 TI - Investigational heptavalent botulinum antitoxin (HBAT) to replace licensed botulinum antitoxin AB and investigational botulinum antitoxin E. AB - CDC announces the availability of a new heptavalent botulinum antitoxin (HBAT, Cangene Corporation) through a CDC-sponsored Food and Drug Administration (FDA) Investigational New Drug (IND) protocol. HBAT replaces a licensed bivalent botulinum antitoxin AB and an investigational monovalent botulinum antitoxin E (BAT-AB and BAT-E, Sanofi Pasteur) with expiration of these products on March 12, 2010. As of March 13, 2010, HBAT became the only botulinum antitoxin available in the United States for naturally occurring noninfant botulism. PMID- 20300058 TI - Use of a reduced (4-dose) vaccine schedule for postexposure prophylaxis to prevent human rabies: recommendations of the advisory committee on immunization practices. AB - This report summarizes new recommendation and updates previous recommendations of the Advisory Committee on Immunization Practices (ACIP) for postexposure prophylaxis (PEP) to prevent human rabies (CDC. Human rabies prevention---United States, 2008: recommendations of the Advisory Committee on Immunization Practices. MMWR 2008;57[No. RR-3]). Previously, ACIP recommended a 5-dose rabies vaccination regimen with human diploid cell vaccine (HDCV) or purified chick embryo cell vaccine (PCECV). These new recommendations reduce the number of vaccine doses to four. The reduction in doses recommended for PEP was based in part on evidence from rabies virus pathogenesis data, experimental animal work, clinical studies, and epidemiologic surveillance. These studies indicated that 4 vaccine doses in combination with rabies immune globulin (RIG) elicited adequate immune responses and that a fifth dose of vaccine did not contribute to more favorable outcomes. For persons previously unvaccinated with rabies vaccine, the reduced regimen of 4 1-mL doses of HDCV or PCECV should be administered intramuscularly. The first dose of the 4-dose course should be administered as soon as possible after exposure (day 0). Additional doses then should be administered on days 3, 7, and 14 after the first vaccination. ACIP recommendations for the use of RIG remain unchanged. For persons who previously received a complete vaccination series (pre- or postexposure prophylaxis) with a cell-culture vaccine or who previously had a documented adequate rabies virus neutralizing antibody titer following vaccination with noncell-culture vaccine, the recommendation for a 2-dose PEP vaccination series has not changed. Similarly, the number of doses recommended for persons with altered immunocompetence has not changed; for such persons, PEP should continue to comprise a 5-dose vaccination regimen with 1 dose of RIG. Recommendations for pre exposure prophylaxis also remain unchanged, with 3 doses of vaccine administered on days 0, 7, and 21 or 28. Prompt rabies PEP combining wound care, infiltration of RIG into and around the wound, and multiple doses of rabies cell-culture vaccine continue to be highly effective in preventing human rabies. PMID- 20300059 TI - Genetic studies of human DNA repair proteins using yeast as a model system. AB - Understanding the roles of human DNA repair proteins in genetic pathways is a formidable challenge to many researchers. Genetic studies in mammalian systems have been limited due to the lack of readily available tools including defined mutant genetic cell lines, regulatory expression systems, and appropriate selectable markers. To circumvent these difficulties, model genetic systems in lower eukaryotes have become an attractive choice for the study of functionally conserved DNA repair proteins and pathways. We have developed a model yeast system to study the poorly defined genetic functions of the Werner syndrome helicase-nuclease (WRN) in nucleic acid metabolism. Cellular phenotypes associated with defined genetic mutant backgrounds can be investigated to clarify the cellular and molecular functions of WRN through its catalytic activities and protein interactions. The human WRN gene and associated variants, cloned into DNA plasmids for expression in yeast, can be placed under the control of a regulatory plasmid element. The expression construct can then be transformed into the appropriate yeast mutant background, and genetic function assayed by a variety of methodologies. Using this approach, we determined that WRN, like its related RecQ family members BLM and Sgs1, operates in a Top3-dependent pathway that is likely to be important for genomic stability. This is described in our recent publication at www.impactaging.com. Detailed methods of specific assays for genetic complementation studies in yeast are provided in this paper. PMID- 20300060 TI - UTX mediates demethylation of H3K27me3 at muscle-specific genes during myogenesis. AB - Polycomb (PcG) and Trithorax (TrxG) group proteins act antagonistically to establish tissue-specific patterns of gene expression. The PcG protein Ezh2 facilitates repression by catalysing histone H3-Lys27 trimethylation (H3K27me3). For expression, H3K27me3 marks are removed and replaced by TrxG protein catalysed histone H3-Lys4 trimethylation (H3K4me3). Although H3K27 demethylases have been identified, the mechanism by which these enzymes are targeted to specific genomic regions to remove H3K27me3 marks has not been established. Here, we demonstrate a two-step mechanism for UTX-mediated demethylation at muscle-specific genes during myogenesis. Although the transactivator Six4 initially recruits UTX to the regulatory region of muscle genes, the resulting loss of H3K27me3 marks is limited to the region upstream of the transcriptional start site. Removal of the repressive H3K27me3 mark within the coding region then requires RNA Polymerase II (Pol II) elongation. Interestingly, blocking Pol II elongation on transcribed genes leads to increased H3K27me3 within the coding region, and formation of bivalent (H3K27me3/H3K4me3) chromatin domains. Thus, removal of repressive H3K27me3 marks by UTX occurs through targeted recruitment followed by spreading across the gene. PMID- 20300061 TI - Daughter cell separation is controlled by cytokinetic ring-activated cell wall hydrolysis. AB - During bacterial cytokinesis, hydrolytic enzymes are used to split wall material shared by adjacent daughter cells to promote their separation. Precise control over these enzymes is critical to prevent breaches in wall integrity that can cause cell lysis. How these potentially lethal hydrolases are regulated has remained unknown. Here, we investigate the regulation of cell wall turnover at the Escherichia coli division site. We show that two components of the division machinery with LytM domains (EnvC and NlpD) are direct regulators of the cell wall hydrolases (amidases) responsible for cell separation (AmiA, AmiB and AmiC). Using in vitro cell wall cleavage assays, we show that EnvC activates AmiA and AmiB, whereas NlpD activates AmiC. Consistent with these findings, we show that an unregulated EnvC mutant requires functional AmiA or AmiB but not AmiC to induce cell lysis, and that the loss of NlpD phenocopies an AmiC(-) defect. Overall, our results suggest that cellular amidase activity is regulated spatially and temporally by coupling their activation to the assembly of the cytokinetic ring. PMID- 20300062 TI - IBRDC2, an IBR-type E3 ubiquitin ligase, is a regulatory factor for Bax and apoptosis activation. AB - Bax, a pro-apoptotic protein from the Bcl-2 family, is central to apoptosis regulation. To suppress spontaneous apoptosis, Bax must be under stringent control that may include regulation of Bax conformation and expression levels. We report that IBRDC2, an IBR-type RING-finger E3 ubiquitin ligase, regulates the levels of Bax and protects cells from unprompted Bax activation and cell death. Downregulation of IBRDC2 induces increased cellular levels and accumulation of the active form of Bax. The ubiquitination-dependent regulation of Bax stability is suppressed by IBRDC2 downregulation and stimulated by IBRDC2 overexpression in both healthy and apoptotic cells. Although mostly cytosolic in healthy cells, upon induction of apoptosis, IBRDC2 accumulates in mitochondrial domains enriched with Bax. Mitochondrial accumulation of IBRDC2 occurs in parallel with Bax activation and also depends on the expression levels of Bcl-xL. Furthermore, IBRDC2 physically interacts with activated Bax. By applying Bax mutants in HCT116 Bax(-/-) cells, combined with the use of active Bax-specific antibodies, we have established that both mitochondrial localization and apoptotic activation of Bax are required for IBRDC2 translocation to the mitochondria. PMID- 20300063 TI - Interaction of MAGED1 with nuclear receptors affects circadian clock function. AB - The circadian clock has a central role in physiological adaption and anticipation of day/night changes. In a genetic screen for novel regulators of circadian rhythms, we found that mice lacking MAGED1 (Melanoma Antigen Family D1) exhibit a shortened period and altered rest-activity bouts. These circadian phenotypes are proposed to be caused by a direct effect on the core molecular clock network that reduces the robustness of the circadian clock. We provide in vitro and in vivo evidence indicating that MAGED1 binds to RORalpha to bring about positive and negative effects on core clock genes of Bmal1, Rev-erbalpha and E4bp4 expression through the Rev-Erbalpha/ROR responsive elements (RORE). Maged1 is a non-rhythmic gene that, by binding RORalpha in non-circadian way, enhances rhythmic input and buffers the circadian system from irrelevant, perturbing stimuli or noise. We have thus identified and defined a novel circadian regulator, Maged1, which is indispensable for the robustness of the circadian clock to better serve the organism. PMID- 20300064 TI - A bacterial effector targets host DH-PH domain RhoGEFs and antagonizes macrophage phagocytosis. AB - Bacterial pathogens often harbour a type III secretion system (TTSS) that injects effector proteins into eukaryotic cells to manipulate host processes and cause diseases. Identification of host targets of bacterial effectors and revealing their mechanism of actions are crucial for understating bacterial virulence. We show that EspH, a type III effector conserved in enteric bacterial pathogens including enteropathogenic Escherichia coli (EPEC), enterohaemorrhagic E. coli and Citrobacter rodentium, markedly disrupts actin cytoskeleton structure and induces cell rounding up when ectopically expressed or delivered into HeLa cells by the bacterial TTSS. EspH inactivates host Rho GTPase signalling pathway at the level of RhoGEF. EspH directly binds the DH-PH domain in multiple RhoGEFs, which prevents their binding to Rho and thereby inhibits nucleotide exchange-mediated Rho activation. Consistently, infection of mouse macrophages with EPEC harbouring EspH attenuates phagocytosis of the bacteria as well as FcgammaR-mediated phagocytosis. EspH represents the first example of targeting RhoGEFs by bacterial effectors, and our results also reveal an unprecedented mechanism used by enteric pathogens to counteract the host defence system. PMID- 20300065 TI - Inhibition of the PtdIns(5) kinase PIKfyve disrupts intracellular replication of Salmonella. AB - 3-phosphorylated phosphoinositides (3-PtdIns) orchestrate endocytic trafficking pathways exploited by intracellular pathogens such as Salmonella to gain entry into the cell. To infect the host, Salmonellae subvert its normal macropinocytic activity, manipulating the process to generate an intracellular replicative niche. Disruption of the PtdIns(5) kinase, PIKfyve, be it by interfering mutant, siRNA-mediated knockdown or pharmacological means, inhibits the intracellular replication of Salmonella enterica serovar typhimurium in epithelial cells. Monitoring the dynamics of macropinocytosis by time-lapse 3D (4D) videomicroscopy revealed a new and essential role for PI(3,5)P(2) in macropinosome-late endosome/lysosome fusion, which is distinct from that of the small GTPase Rab7. This PI(3,5)P(2)-dependent step is required for the proper maturation of the Salmonella-containing vacuole (SCV) through the formation of Salmonella-induced filaments (SIFs) and for the engagement of the Salmonella pathogenicity island 2 encoded type 3 secretion system (SPI2-T3SS). Finally, although inhibition of PIKfyve in macrophages did inhibit Salmonella replication, it also appears to disrupt the macrophage's bactericidal response. PMID- 20300066 TI - Genetic influence on baroreflex sensitivity in normotensive young men. AB - BACKGROUND: The dysfunction of baroreflex plays an important role in the pathogenesis of essential hypertension. Recent studies suggest that approximately 40% of the variation in baroreflex sensitivity (BRS) may be accounted for by genetic factors. However, only a few such genetic polymorphisms have been explicitly identified. METHODS: A total of 182 normotensive young men were included in the study. They were tested for the occurrence of genotypes involving nine polymorphisms in six genes that have a role in the regulation of the cardiovascular system. BRS was calculated from the spontaneous fluctuation of systolic blood pressure (SBP) and heart interval, using a sequence method. RESULTS: BRS was negatively correlated with body mass index (BMI), SBP, and family history of hypertension. Univariate analysis revealed that BRS is significantly associated with three of the polymorphisms studied. At the polymorphism T-786C in the endothelial nitric oxide (NO) synthase (eNOS) gene, the subjects with TT genotype had lower BRS than subjects carrying either the TC or the CC genotype. At the polymorphism of C-344T in the aldosterone synthase gene (CYP11B2), subjects with the TT genotype had higher BRS as compared to those with CC. At the polymorphism of T-58C in the bradykinin B2 receptor (B2R) gene, subjects with CC genotype had lower BRS as compared to subjects with TT. A multivariable linear regression analysis indicated that 16% of the BRS variation could be explained by these three polymorphisms. CONCLUSIONS: Baroreflex function plays an important role in regulating blood pressure, both in the short term and in the long term. Three polymorphisms that are associated with the variation in BRS were identified in the eNOS, CYP11B2, and B2R genes, respectively; overall, they accounted for 16% of the BRS variation. PMID- 20300068 TI - Hypertension, prehypertension, and transient elevated blood pressure in children: association with weight excess and waist circumference. AB - BACKGROUND: To assess the prevalence of hypertension (H), prehypertension (PH), and transient elevated blood pressure (TH) and their relationship with weight class and waist circumference (WC) in an unselected population of Northern Italian children. METHODS: A cross-sectional study was conducted in 5,131 children (5-11 years). Weight class was defined according to the International Obesity Task Force references, H and PH according to the National High Blood Pressure Education Program. A child was classified as having PH or H when systolic blood pressure (SBP) and/or diastolic blood pressure (DBP) at first screening were > or =90th percentile and the mean of three subsequent measures was between the 90th and 95th or > or =95th percentile, respectively. When BP values at the first screening were > or =90th percentile but the mean of three subsequent measures was <90th percentile the child was classified as having TH. RESULTS: A proportion of 3.4% presented H, 2.7% PH, and 10.4% TH, 20% overweight, and 6% obesity. Weight class and WC were significantly associated to an increased risk of falling into any of the hypertensive categories. In children with TH BP z scores of the mean of the three subsequent measurements following the first screening were significantly higher than BP z-scores observed in normotensive children (P value <0.001). CONCLUSIONS: Weight class and WC are associated with BP. This is observed not only for H but also for PH, and for nonsustained forms of H. Prospective studies are needed to assess whether children with PH and TH will develop sustained H. PMID- 20300067 TI - Inhibition of angiotensin-converting enzyme 2 exacerbates cardiac hypertrophy and fibrosis in Ren-2 hypertensive rats. AB - BACKGROUND: Emerging evidence suggests that cardiac angiotensin-converting enzyme 2 (ACE2) may contribute to the regulation of heart function and hypertension induced cardiac remodeling. We tested the hypothesis that inhibition of ACE2 in the hearts of (mRen2)27 hypertensive rats may accelerate progression of cardiac hypertrophy and fibrosis by preventing conversion of angiotensin II (Ang II) into the antifibrotic peptide, angiotensin-(1-7) (Ang-(1-7)). METHODS: Fourteen male (mRen2)27 transgenic hypertensive rats (12 weeks old, 401 + or - 7 g) were administered either vehicle (0.9% saline) or the ACE2 inhibitor, MLN-4760 (30 mg/kg/day), subcutaneously via mini-osmotic pumps for 28 days. RESULTS: Although ACE2 inhibition had no effect on average 24-h blood pressures, left ventricular (LV) Ang II content increased 24% in rats chronically treated with the ACE2 inhibitor (P < 0.05). Chronic ACE2 inhibition had no effect on plasma Ang II or Ang-(1-7) levels. Increased cardiac Ang II levels were associated with significant increases in both LV anterior, posterior, and relative wall thicknesses, as well as interstitial collagen fraction area and cardiomyocyte hypertrophy in the transgenic animals chronically treated with the ACE2 inhibitor. Cardiac remodeling was not accompanied by any further alterations in LV function. CONCLUSIONS: These studies demonstrate that chronic inhibition of ACE2 causes an accumulation of cardiac Ang II, which exacerbates cardiac hypertrophy and fibrosis without having any further impact on blood pressure or cardiac function. PMID- 20300069 TI - TrkB agonist antibody dose-dependently raises blood pressure in mice with diet induced obesity. AB - BACKGROUND: Brain-derived neurotrophic factor (BDNF) regulates food intake and body weight, but is not useful as a therapeutic because of its short half-life. Chronic activation of its receptor, tyrosine kinase receptor B (TrkB), represents an alternative strategy for lowering body weight. However, because BDNF can raise blood pressure (BP) acutely, it is possible that chronic TrkB activation will produce adverse cardiovascular effects. METHODS: We used radiotelemetry to test whether treatment with a TrkB agonist antibody (Ab) causes adverse cardiovascular effects in mice with diet-induced obesity. RESULTS: High-dose (1 mg/kg) TrkB Ab reduced body weight and significantly increased BP, whereas low-dose (0.3 mg/kg) treatment lowered body weight without adverse cardiovascular effects. Rimonabant, through a different mechanism of action, lowered body weight in this model more than TrkB activation, but showed no adverse effects on heart rate (HR) or BP. These data suggest that elevated BP was a direct effect of high-dose TrkB Ab treatment rather than secondary to substantial weight loss. CONCLUSIONS: Overall, high-dose TrkB Ab lowered body weight and increased BP, whereas low-dose TrkB Ab treatment caused therapeutic weight loss without adverse cardiovascular effects. We conclude that TrkB activation dose-dependently lowers body weight and transiently raises BP in mice with diet-induced obesity. PMID- 20300070 TI - A cross-national comparative study of blood pressure and hypertension between English and Dutch South-Asian- and African-origin populations: the role of national context. AB - BACKGROUND: We compare patterns of blood pressure (BP) and prevalence of hypertension between white-Dutch and their South-Asian and African minority groups with their corresponding white-English and their South-Asian and African ethnic minority groups; and the contribution of physical activity, body sizes, and socioeconomic position (SEP); and the quality of BP treatment that may underlie differences in mean BP. METHODS: Secondary analyses of population-based studies of 13,999 participants from the United Kingdom and the Netherlands. RESULTS: Compared with Dutch South-Asians, all English South-Asian men and women had lower BP and prevalence of hypertension except for systolic BP in English Indian men. Among Africans, the systolic BP did not differ, but the diastolic BP levels were lower in English-Caribbean and English- (sub-Sahara) African men and women than in their Dutch-African counterparts. English-Caribbeans had a lower prevalence of hypertension than Dutch-Africans. Compared with white-Dutch, white English men and women had higher systolic BP levels, but lower diastolic BP levels. There were no differences in the prevalence of hypertension between the white groups. Most differences remained unchanged after adjustment for SEP, lifestyle, and body sizes in all ethnic groups. BP control rates were substantially lower among Dutch-African and Dutch South-Asian hypertensives than among their English counterparts (except Indians). CONCLUSIONS: We found marked variations in BP and hypertension prevalence between comparable ethnic groups in England and the Netherlands. Poor BP control among Dutch South-Asians and Africans contributed to their disadvantage of the relatively high BP levels. PMID- 20300071 TI - Fruits and vegetables intake and physical activity among hypertensive adults in the United States: behavioral risk factor surveillance system, 2003 and 2007. AB - BACKGROUND: Consuming enough fruits and vegetables and engaging in regular physical activity are believed to be two important components of several lifestyle modifications for people with hypertension. The purpose of this study was to measure the degree to which US adults with hypertension achieved recommended intakes of fruits and vegetables and engaged in recommended levels of physical activity in 2003 and 2007. METHODS: Using the Behavioral Risk Factor Surveillance System (BRFSS) data conducted in 2003 (N = 264,178) and 2007 (N = 430,082), we determined the changes in the prevalence of eating > or =5 servings of fruits and vegetables and of obtaining Healthy People 2010 recommended level of physical activity among adults with hypertension during the period. RESULTS: In 2003 and 2007, among individuals with hypertension, age-adjusted prevalences of eating > or =5 servings of fruits and vegetables were 23.8 and 24.4% (P = 0.394) and meeting a recommended physical activity level were 38.2 and 40.3% (P < 0.001). With 2003 as the reference, odds ratios (95% confidence interval) of eating > or =5 servings of fruits and vegetables and meeting a recommended physical activity for 2007 were 1.02 (0.97-1.08) and 1.06 (1.01-1.10), respectively, after adjusting for relevant factors. CONCLUSIONS: Among hypertensives, less than a quarter are eating five or more servings of fruits and vegetables per day, and less than half are meeting recommended physical activity. In 4 years, there was no statistically significant improvement in intake of fruits and vegetables and just a slight, albeit statistically significant, improvement in physical activity among US adults. PMID- 20300072 TI - Effect of pressure overload on cardioprotection via PI3K-Akt: comparison of postconditioning, insulin, and pressure unloading. AB - BACKGROUND: Postconditioning (PC) and insulin exert cardioprotection by activating phosphatidylinositol-3 kinase (PI3K) signaling. Because pressure overload exacerbates ischemia-reperfusion (IR) injury, we tested the hypothesis that (i) pressure overload attenuates PC- and insulin-induced cardioprotection, an effect caused by reduced PI3K-Akt signaling and (ii) pressure unloading confers cardioprotection comparable to either PC or insulin. METHODS: Infarct size (IS) and levels of relevant proteins (i.e., Akt, glycogen synthase kinase 3beta (GSK-3beta), 3'-phosphoinositide dependent kinase 1 (PDK1), phosphatase and tensin homolog on chromosome ten (PTEN)) were determined in hearts subjected to IR. RESULTS: Pressure overload increased IS in association with changes in protein levels consistent with reduced PI3K-Akt signaling (i.e., ischemic reperfused vs. normoxic hearts). PC and insulin reduced IS but it was greater in hearts perfused at the higher, than the lower, pressure. Wortmannin (PI3K inhibitor) partially reversed PC-induced cardioprotection, with IS being greater in the high-pressure group. Pressure unloading during reperfusion caused the most marked reduction in IS whereas pressure loading abolished PC-induced cardioprotection. Nonetheless, the phospho-Akt/total Akt ratios and phospho-GSK 3beta levels were unaffected by perfusion pressure in insulin-treated or postconditioned hearts. Moreover, protein levels were similar in pressure unloaded and pressure-loaded hearts. CONCLUSIONS: Pressure overload reduces PI3K Akt signaling following IR. However, a differential in PI3K-Akt signaling was not observed in ischemia-reperfused, insulin-treated, and postconditioned hearts, suggesting involvement of pathways other than PI3K-Akt for the effect of pressure on IS. Importantly, pressure unloading at reperfusion represents a novel and effective cardioprotective maneuver. PMID- 20300073 TI - The effect of pulse rate and blood pressure dipping status on the risk of stroke and cardiovascular disease in Japanese hypertensive patients. AB - BACKGROUND: There have been few reports on the relationship between variation in the diurnal pulse rate (PR) in relation to a nondipper blood pressure (BP) pattern and cardiovascular events in elderly hypertensives. METHODS: Ambulatory BP monitoring (ABPM) was conducted at baseline in 811 older Japanese hypertensives (clinical BP >140/90 mm Hg; age >50 years old) enrolled in the Jichi Medical School ABPM study, wave 1. They were followed up for an average of 41 months, and the incidence of subsequent cardiovascular event and death was evaluated. PR nondipping status was defined as (awake PR - sleep PR)/awake PR <0.1. RESULTS: The mean age of patients was 72.3 +/- 9.8 years (311 men and 500 women). The nondipper patients had a higher risk of cardiovascular events (11.5% vs. 6.1%, P = 0.006) and stroke (9.9% vs. 5.7%, P = 0.039) than the dippers. Patients were classified into four subgroups: BP dipping plus PR dipping status (n = 471), BP dipping plus PR nondipping (n = 37), BP nondipping plus PR dipping (n = 250), and BP nondipping plus PR nondipping (n = 53). The combination of BP and PR nondipping constituted a higher risk of cardiovascular events and stroke than the other three combinations combined (cardiovascular events: 17.0% vs. 7.5%, P = 0.015; stroke: 17.0% vs. 6.6%, P = 0.005). On Cox proportional hazards modeling, BP nondipping with PR nondipping led to a significant synergistic increase in the risk of stroke (hazard ratio: 8.92; 95% confidence interval: 1.03 77.5, P = 0.048). CONCLUSIONS: A blunted PR dip might predict a stroke in elderly hypertensives with a nondipping BP status. PMID- 20300074 TI - Risk of progression to hypertension in a rural Chinese women population with prehypertension and normal blood pressure. AB - BACKGROUND: To determine the incidence of hypertension and its risk factors among rural Chinese women with prehypertension and normotension. METHODS: A population based sample of 12,060 rural Chinese women aged > or = 35 years and free from hypertension at baseline were followed from 2004-2006 to 2008. Incident hypertension was defined as systolic blood pressure (SBP) > or = 140 mm Hg, diastolic blood pressure (DBP) > or = 90 mm Hg, or current use of antihypertensive medication. RESULTS: Over a median follow-up of 28 months (range, 14-47 months), 23.4% of women developed hypertension. The age-adjusted incidence rate was higher in prehypertension than in normotension (11.2/100 person-years vs. 7.9/100 person-years, P < 0.05). Among women with prehypertension, independent predictors of incident hypertension were baseline age, Mongolian ethnicity, low physical activity, baseline body mass index (BMI), baseline salt intake and family history of hypertension. Among women with normal blood pressure (BP), independent predictors were baseline age, low physical activity, baseline BMI and baseline salt intake. The awareness, treatment, and control rates for newly developed hypertension were 33.2, 23.0, and 2.1%, respectively. CONCLUSIONS: These data indicate that the incidence of hypertension is high among rural Chinese women and it is associated with many risk factors, and the data also suggest that most newly developed hypertension cases are not treated. This high incidence of hypertension may be related to rapid social changes in our country and may apply to other areas of the developing world. These results call for urgent improvements in hypertension prevention, detection and treatment. PMID- 20300076 TI - Low-grade systemic inflammation, arterial structure and function, and hypertension. PMID- 20300079 TI - The effect of the interleukin-1 cytokine family members IL-1F6 and IL-1F8 on adipocyte differentiation. AB - Obesity is characterized by chronic low-grade inflammation originating from expanding adipose tissue. In the present study, we examined the adipogenic expression levels of IL-1F6 and IL-1F8, both members of the IL-1 family of cytokines, and their effects on adipose tissue gene expression. Although IL-1F6 is primarily present in adipose tissue resident macrophages and induced by inflammation, IL-1F8 is absent. IL-1F6, but not IL-1F8, reduces adipocyte differentiation, as shown by a significant decrease in PPARgamma gene expression. Finally, both IL-1F6 and IL-1F8 are able to induce inflammatory gene expression in mature adipocytes. In conclusion, we demonstrate for the first time that IL 1F6 is present in adipose tissue and that IL-1F6 and IL-1F8 are involved in the regulation of adipose tissue gene expression. Importantly, IL-1F6 inhibits PPARgamma expression which may lead to reduced adipocyte differentiation suggesting metabolic effects of this cytokine. PMID- 20300080 TI - Improvements in coronary heart disease risk indicators by alternate-day fasting involve adipose tissue modulations. AB - The ability of alternate-day fasting (ADF) to modulate adipocyte parameters in a way that is protective against coronary heart disease (CHD) has yet to be tested. Accordingly, we examined the effects of ADF on adipokine profile, body composition, and CHD risk indicators in obese adults. Sixteen obese subjects (12 women/4 men) participated in a 10-week trial with three consecutive dietary intervention phases: (i) 2-week baseline control phase, (ii) 4-week ADF controlled feeding phase, and (iii) 4-week ADF self-selected feeding phase. After 8 weeks of treatment, body weight and waist circumference were reduced (P < 0.05) by 5.7 +/- 0.9 kg, and 4.0 +/- 0.9 cm, respectively. Fat mass decreased (P < 0.05) by 5.4 +/- 0.8 kg, whereas fat-free mass did not change. Plasma adiponectin was augmented (P < 0.05) by 30% from baseline. Leptin and resistin concentrations were reduced (P < 0.05) by 21 and 23%, respectively, post treatment. Low-density lipoprotein cholesterol (LDL-C) and triacylglycerol concentrations were 25% and 32% lower (P < 0.05), respectively, after 8 weeks of ADF. High-density lipoprotein cholesterol (HDL-C), C-reactive protein, and homocysteine concentrations did not change. Decreases in LDL-C were related to increased adiponectin (r = -0.61, P = 0.01) and reduced waist circumference (r = 0.39, P = 0.04). Lower triacylglycerol concentrations were associated with augmented adiponectin (r = -0.39, P = 0.04) and reduced leptin concentrations (r = 0.45, P = 0.03) post-treatment. These findings suggest that adipose tissue parameters may play an important role in mediating the cardioprotective effects of ADF in obese humans. PMID- 20300081 TI - Obesity reduction black intervention trial (ORBIT): 18-month results. AB - Obesity is a chronic condition that is prevalent in black women. The Obesity Reduction Black Intervention Trial (ORBIT) was a randomized controlled weight loss and weight-loss maintenance (WLM) trial. Participants (N = 213) were randomized to the intervention or control groups in August 2005 and September 2006. Follow-up data were collected 6 and 18 months after randomization. The main outcome was change in weight and BMI from baseline to 18 months. The mean weight at baseline was 104.9 kg, and the mean weight loss in the intervention group at 6 months was 3.0 kg and a gain of 0.2 kg in the control group (mean difference between groups in weight change at 6 months, adjusting for baseline weight and cohort, -3.27 kg; 95% confidence interval (CI), -4.50 to -2.05 kg; P < 0.001). Both groups gained weight between 6 and 18 months (mean 1.0 kg in the intervention group and 0.1 kg in the control group). However, intervention participants lost significantly more weight than control participants during the 18-month intervention (adjusted mean difference between groups at 18 months, 2.83 kg; 95% CI, -4.71 to -0.95; P = 0.003). At 18 months, intervention participants were more likely than control participants to have lost at least 5% of baseline weight (24% vs. 12%, P < 0.04). Our results indicate that the ORBIT program did promote weight loss and weight-loss maintenance. However, the results also clearly illustrate there is more to learn about what will contribute to meaningful weight loss and maintenance in this population. PMID- 20300082 TI - A model of binge-like eating behavior in mice that does not require food deprivation or stress. AB - Binge eating disorder (BED) is characterized by excessive food intake during a short period of time and is often associated with obesity. Mouse models of binge like eating behavior are lacking making it difficult to employ genetic models in the identification of mechanisms regulating excessive eating. We report a rapid and simple model to induce binge-like eating behavior in mice that does not require food deprivation or exogenous stressors. Weekly 24 h access to a nutritionally complete high energy diet (HED), along with continuous access to standard chow, resulted in a significant increase in HED intake following its presentation compared to mice that had continuous access to both diets. Mice exhibiting binge-like eating consumed one-third of their normal total daily caloric intake within 2.5 h of HED presentation. Moreover, total 24-h caloric intakes were increased by 50% in mice exhibiting binge-like eating. Following repeated cycles, binge-like eating of the HED was maintained over several weeks with no evidence of habituation or significant alterations in body weight and adiposity. Pharmacological evaluation of binge-like eating behavior was performed using clinically employed compounds. Interestingly, binge-like eating was dose dependently decreased by fluoxetine, but not baclofen or topiramate. These data support clinical validation of this mouse model of binge-like eating behavior, as fluoxetine has been shown to reduce binge frequency in human subjects with BED. The availability of transgenic and knockout mice will allow for the determination of genes that are involved in the initiation and maintenance of binge-like eating behavior. PMID- 20300083 TI - Adiposity and beta-cell function: relationships differ with ethnicity and age. AB - The prevalence of type 2 diabetes is higher among African Americans (AA) vs. European Americans (EA), is highest at middle age, and is related to obesity. This study was conducted to test the hypothesis that the association of adiposity (percent body fat (%fat)) with indexes of insulin sensitivity (S(I)) and beta cell function would differ with ethnicity and age. Subjects were 168 healthy, normoglycemic AA and EA girls and women aged 7-12 years, 18-32 years, and 40-70 years. An intravenous glucose tolerance test (IVGTT) was used to assess indexes of insulin secretion and action: S(I), acute C-peptide secretion (X0); basal, first-phase, second-phase, and total beta-cell responsivity to glucose (PhiB, Phi1, Phi2, and Phi(TOT), respectively); and the disposition index (DI = S(I) * Phi(TOT)). %Fat was assessed with dual energy X-ray absorptiometrys. Adiposity was significantly associated with S(I) among EA (-0.57, P < 0.001) but not AA ( 0.20, P = 0.09). Adiposity appeared stimulatory to beta-cell function in the two groups of younger subjects and in EA, but inhibitory in postmenopausal women, particularly AA postmenopausal women. Among AA postmenopausal women, %fat was inversely associated with Phi1 (r = -0.57, P < 0.05) and Phi(TOT) (r = -0.68, P < 0.01). These results suggest that the impact of adiposity on insulin secretion and action differs with age and ethnicity. PMID- 20300084 TI - Sex- and depot-dependent differences in adipogenesis in normal-weight humans. AB - To elucidate cellular mechanisms of sex-related differences in fat distribution, we determined body fat distribution (dual-energy X-ray absorptiometry and single slice abdominal computed tomography (CT)), adipocyte size, adipocyte number, and proportion of early-differentiated adipocytes (aP2(+)CD68(-)) in the stromovascular fraction (SVF) in the upper and lower body of normal-weight healthy men (n = 12) and premenopausal women (n = 20) (age: 18-49 years, BMI: 18 26 kg/m(2)). Women had more subcutaneous and less visceral fat than men. The proportion of early differentiated adipocytes in the subcutaneous adipose tissue SVF of women was greater than in men (P = 0.01), especially in the femoral depot, although in vitro adipogenesis, as assessed by peroxisome proliferator activated receptor-gamma (PPARgamma) expression, was not increased in femoral preadipocytes cultured from women compared with men. In women, differentiation of femoral preadipocytes was less than that of abdominal subcutaneous preadipocytes (P = 0.04), and femoral subcutaneous preadipocytes tended to be more resistant to tumor necrosis factor-alpha (TNFalpha)-induced apoptosis (P = 0.06). Thus, turnover and utilization of the preadipocyte pool may be reduced in lower vs. the upper-body fat in women. Collectively, these data indicate that the microenvironment, rather than differences in inherent properties of preadipocytes between genders, may explain the gynoid obesity phenotype and higher percent body fat in women compared to men. PMID- 20300085 TI - Quantification of intermuscular adipose tissue in the erector spinae muscle by MRI: agreement with histological evaluation. AB - Deposition of fat between skeletal muscle bundles and beneath the muscle fascia, recently called intermuscular adipose tissue (IMAT), is gaining attention as potential contributor to insulin resistance, metabolic syndrome, muscle function impairment, and disability. The aim of this study was to compare IMAT as measured at the erector spinae level by magnetic resonance imaging (MRI), a well recognized gold standard method to evaluate fat content inside muscles, and histology estimates. In 18 healthy elderly men and women with a wide range of BMI (25.05-35.58 kg/m(2)), undergoing elective vertebral surgery, IMAT within the erector spinae muscle was evaluated by MRI, by body composition using dual-energy X-ray absorptiometry and histological evaluation of intraoperative biopsy sample. The concordance between IMAT/total area (TA) ratio evaluated by MRI and histological examination was analyzed employing Lin's concordance correlation coefficient and the procedure proposed by Bland and Altman. Two thresholds to distinguish between muscle and IMAT calculated, respectively, by 20 and 10% reduction of the gray-level intensity evaluated by MRI from surrounding subcutaneous adipose tissue (SAT) were used. With a 20% reduction, calculated IMAT/TA as evaluated by MRI on average exceeds histological evaluation by 21.79%, whereas by reducing the threshold by 10% agreement between MRI and histology improved with a 12.42% difference. Our data show a good degree of concordance between IMAT assessment by MRI and histology and seems to show that agreement between the two methods could be improved by using a more restrictive threshold between muscle and fat. PMID- 20300086 TI - Plasma epinephrine predicts fasting glucose in centrally obese African-American women. AB - The high prevalence of diabetes in African-American (AA) women has been widely assumed to be related to the greater prevalence of obesity in this group. Catecholamine release acting on central adipose tissue has been proposed to be a contributing factor. The aim of this article was to examine the interaction of plasma catecholamines and central adiposity on fasting and nonfasting glucose levels in two separate samples. In both studies, the women were healthy, nondiabetic of similar age. In addition, both studies assessed plasma epinephrine (EPI) and norepinephrine (NOREPI) levels collected at three time points. In study 1, catecholamines were measured during a standardized laboratory mental stress task and in study 2, they were measured during the initial phase (10 min) of an intravenous glucose tolerance test (IVGTT). Results from both studies revealed significant effects of EPI on fasting glucose in the obese women. In study 1, mean EPI levels were significantly related to fasting glucose in AA women with high trunk fat (beta = 0.60, P < 0.001). Because high BMI was associated with high trunk fat in women, we used BMI >30 as a proxy for high trunk fat (>32%) in study 2. In study 2, EPI response to the glucose bolus was a strong predictor of fasting glucose in AA women with BMI >30 (beta = 0.75, P < 0.003). We conclude that the effect of central adiposity on fasting glucose may be moderated by plasma EPI. This suggests that adrenal medullary activity could play a role in the pathophysiology of type 2 diabetes. PMID- 20300087 TI - The effect of surgical weight reduction on left ventricular structure and function in severe obesity. AB - The aim of this study was to examine the effect of surgical weight reduction on cardiac structure and function and to seek the determinants of these changes. Sixty-six severely obese adults (BMI >or=35 kg/m(2)) who received bariatric surgery underwent echocardiographic examination before and 3 months after surgery. At 3 months after surgery, BMI and systolic blood pressure (BP) decreased (43.3 +/- 6.3 to 34.1 +/- 5.6 kg/m(2), P < 0.001, and 146 +/- 12 to 130 +/- 14 mm Hg, P < 0.001, respectively). In left ventricular (LV) geometry, the relative wall thickness (RWT) and LV mass index decreased significantly (0.43 +/- 0.05 to 0.35 +/- 0.05, P < 0.001, and 50 +/- 11 to 39 +/- 11 g/m(2.7), P < 0.001, respectively) without changes in chamber size. Multivariate analyses showed change in systolic BP to be an independent predictor for the changes in RWT and LV mass index. In myocardial performance, peak systolic mitral annular velocity and all diastolic indexes showed significant improvements. We concluded that LV hypertrophy and function improved rapidly after bariatric surgery in severely obese adults. BP reduction was the major determinant for the regression of LV hypertrophy in the early stage of surgical weight reduction. PMID- 20300088 TI - Genome-wide association studies in pharmacogenomics. AB - Genome-wide association (GWA) studies for pharmacogenomics-related traits are increasingly being performed to identify loci that affect either drug response or susceptibility to adverse drug reactions. Until now, only the largest effects have been detected, partly because of the challenges of obtaining large numbers of cases for pharmacogenomic studies. Since 2007, a range of pharmacogenomics GWA studies have been published that have identified several interesting and novel associations between drug responses or reactions and clinically relevant loci, showing the value of this approach. PMID- 20300090 TI - What's in a review? PMID- 20300089 TI - Chromatin structure and the inheritance of epigenetic information. AB - Although it is widely accepted that the regulation of the chromatin landscape is pivotal to conveying the epigenetic program, it is still unclear how a defined chromatin domain is reproduced following DNA replication and transmitted from one cell generation to the next. Here, we review the multiple mechanisms that potentially affect the inheritance of epigenetic information in somatic cells. We consider models of how histones might be recycled following replication, and discuss the importance of positive-feedback loops, long-range gene interactions and the complex network of trans-acting factors in the transmission of chromatin states. PMID- 20300092 TI - The genetic code: an archaeal path to literacy. PMID- 20300093 TI - Kinase inhibitors: narrowing down the real targets. PMID- 20300094 TI - Biosynthesis: unmasking morphine. PMID- 20300095 TI - Channels: flies feel your pain. PMID- 20300101 TI - Do astrocytes really exocytose neurotransmitters? AB - In the past 20 years, an extra layer of information processing, in addition to that provided by neurons, has been proposed for the CNS. Neuronally evoked increases of the intracellular calcium concentration in astrocytes have been suggested to trigger exocytotic release of the 'gliotransmitters' glutamate, ATP and D-serine. These are proposed to modulate neuronal excitability and transmitter release, and to have a role in diseases as diverse as stroke, epilepsy, schizophrenia, Alzheimer's disease and HIV infection. However, there is intense controversy about whether astrocytes can exocytose transmitters in vivo. Resolving this issue would considerably advance our understanding of brain function. PMID- 20300102 TI - Modelling the molecular mechanisms of synaptic plasticity using systems biology approaches. AB - Synaptic plasticity is thought to underlie learning and memory, but the complexity of the interactions between the ion channels, enzymes and genes that are involved in synaptic plasticity impedes a deep understanding of this phenomenon. Computer modelling has been used to investigate the information processing that is performed by the signalling pathways involved in synaptic plasticity in principal neurons of the hippocampus, striatum and cerebellum. In the past few years, new software developments that combine computational neuroscience techniques with systems biology techniques have allowed large-scale, kinetic models of the molecular mechanisms underlying long-term potentiation and long-term depression. We highlight important advancements produced by these quantitative modelling efforts and introduce promising approaches that use advancements in live-cell imaging. PMID- 20300104 TI - The regulatory crosstalk between kinases and proteases in cancer. AB - Kinases and proteases are responsible for two fundamental regulatory mechanisms- phosphorylation and proteolysis--that orchestrate the rhythms of life and death in all organisms. Recent studies have highlighted the elaborate interplay between both post-translational regulatory systems. Many intracellular or pericellular proteases are regulated by phosphorylation, whereas multiple kinases are activated or inactivated by proteolytic cleavage. The functional consequences of this regulatory crosstalk are especially relevant in the different stages of cancer progression. What are the clinical implications derived from the fertile dialogue between kinases and proteases in cancer? PMID- 20300105 TI - Cell line-based platforms to evaluate the therapeutic efficacy of candidate anticancer agents. AB - Efforts to discover new cancer drugs and predict their clinical activity are limited by the fact that laboratory models to test drug efficacy do not faithfully recapitulate this complex disease. One important model system for evaluating candidate anticancer agents is human tumour-derived cell lines. Although cultured cancer cells can exhibit distinct properties compared with their naturally growing counterparts, recent technologies that facilitate the parallel analysis of large panels of such lines, together with genomic technologies that define their genetic constitution, have revitalized efforts to use cancer cell lines to assess the clinical utility of new investigational cancer drugs and to discover predictive biomarkers. PMID- 20300107 TI - Pitavastatin reduces oxidative stress and attenuates intermittent hypoxia-induced left ventricular remodeling in lean mice. AB - We have reported previously that intermittent hypoxia related to sleep apnea induces cardiovascular remodeling secondary to the oxidative stress. The aim of this study was to examine the effect of pitavastatin as an antioxidant to prevent intermittent hypoxia-induced left ventricular (LV) remodeling in mice without hypercholesterolemia. Eight-week-old male C57BL/6J mice (n=35) were exposed to intermittent hypoxia (30 s exposure to 5% oxygen, followed by 30 s exposure to 21% oxygen) for 8 h per day during the daytime or maintained under normoxic conditions; in addition, they were either treated with pitavastatin (3 mg kg(-1) per day) or vehicle for 10 days. After cardiac catheterization and blood sampling, the LV myocardium was examined. The systemic blood pressure and plasma level of total cholesterol were similar among the four groups. Intermittent hypoxia significantly increased the expression levels of 4-hydroxy-2-nonenal (4 HNE) proteins, TNF-alpha and TGF-beta mRNA, and also the number of terminal deoxynucleotidyl transferase-mediated dUTP-biotin end labeling (TUNEL)-positive myocardial cells in the LV myocardium. In addition, enhanced hypertrophy of the cardiomyocytes, perivascular fibrosis and histological degeneration were observed in the mice exposed to hypoxic stress. Treatment with pitavastatin significantly suppressed the expression levels of the 4-HNE proteins, cytokines, superoxide production and TUNEL-positive myocardial cells in the LV myocardium, consequently attenuating the hypoxia-induced histological changes. Pitavastatin preserved, at least partially, the morphological structure of the LV myocardium in lean mice exposed to intermittent hypoxia, through its antioxidant effect. PMID- 20300108 TI - Increasing adherence: is that enough? PMID- 20300109 TI - Seasonal variation in metabolic syndrome prevalence. AB - Accumulating evidence has shown that seasonal variations can exist within metabolic syndrome parameters. The aim of this study was to examine the hypothesis that there are seasonal variations in the prevalence of metabolic syndrome in Japanese subjects. We investigated a total of 1202 male workers in our institution (44+/-10 years) who underwent health checkups in both June (summer) and December (winter) 2008. In this study, metabolic syndrome was defined according to the criteria proposed by the National Cholesterol Education Program (NCEP), the International Diabetes Federation (IDF) and the Japanese Society of Internal Medicine (JSIM). Serum levels of high-density lipoprotein cholesterol and fasting glucose, as well as blood pressure (BP), were significantly higher in winter than in summer, whereas waist circumference and serum levels of triglyceride exhibited little change. The prevalence rates of NCEP, IDF, and JSIM metabolic syndrome in this study were 3.8, 15.1 and 12.4% in winter and 3.2, 10.7 and 8.4% in summer, respectively. Of all metabolic syndrome components, an elevated BP was most significantly correlated with the seasonal variation of metabolic syndrome prevalence. This study demonstrated seasonal variations in metabolic syndrome prevalence in Japanese male workers. These results indicate that the season of health checkups may affect the clinical diagnosis and management of metabolic syndrome. PMID- 20300106 TI - Targeting metabolic transformation for cancer therapy. AB - Cancer therapy has long relied on the rapid proliferation of tumour cells for effective treatment. However, the lack of specificity in this approach often leads to undesirable side effects. Many reports have described various 'metabolic transformation' events that enable cancer cells to survive, suggesting that metabolic pathways might be good targets. There are currently several drugs under development or in clinical trials that are based on specifically targeting the altered metabolic pathways of tumours. This Review highlights pathways against which there are already drugs in different stages of development and also discusses additional druggable targets. PMID- 20300110 TI - Cystatin B inhibition of TRAIL-induced apoptosis is associated with the protection of FLIP(L) from degradation by the E3 ligase itch in human melanoma cells. AB - Past studies have identified a number of distinct mechanisms that contribute to the resistance of melanoma cells against apoptosis induced by TNF-related apoptosis-inducing ligand (TRAIL). In this report we show that cystatin B is another endogenous inhibitor of TRAIL-induced apoptosis. Cystatin B-deficient melanoma cell lines established by shRNA knockdown displayed increased apoptosis that was associated with enhanced activation of caspase-8 induced by TRAIL. This was not related to the inhibitory effect of cystatin B on the lysosomal cysteine proteases, cathepsin B and L, as they did not have a role in TRAIL-induced apoptosis in most melanoma cell lines even when cystatin B was inhibited. Instead, sensitization of melanoma cells to TRAIL-induced apoptosis by inhibition of cystatin B appeared associated with decreased stability of FLIP(L) as the levels of FLIP(L) were reduced because of shortened half-life time in melanoma cells deficient in cystatin B. In contrast, over-expression of cystatin B increased the levels of FLIP(L), decreased the amount of the E3 ligase Itch associated with FLIP(L), and reduced FLIP(L) ubiquitination. Inhibition of Itch by siRNA restored the levels of FLIP(L) and blocked sensitization to TRAIL induced apoptosis associated with deficiency in cystatin B. Taken together, these results indicate that cystatin B regulates Itch-mediated degradation of FLIP(L) and thereby TRAIL-induced apoptosis in melanoma cells. PMID- 20300111 TI - Jun and JunD-dependent functions in cell proliferation and stress response. AB - Jun is essential for fetal development, as fetuses lacking Jun die at mid gestation with multiple cellular defects in liver and heart. Embryos expressing JunD in place of Jun (Jun(d/d)) can develop to term with normal fetal livers, but display cardiac defects as observed in fetuses lacking Jun. Jun(d/d) mouse embryonic fibroblasts (MEFs) exhibit early senescence, which can be rescued by EGF and HB-EGF stimulation, probably through activation of Akt signaling. Thus, JunD cannot functionally replace Jun in regulating fibroblast proliferation. In Jun(-/-) fetal livers, increased hydrogen peroxide levels are detected and expression of Nrf1 and Nrf2 (nuclear erythroid 2-related transcription factors) is downregulated. Importantly, increased oxidative stress as well as expression of Nrf1 and Nrf2 is rescued by JunD in Jun(d/d) fetal livers. These data show that Jun is of critical importance for cellular protection against oxidative stress in fetal livers and fibroblasts, and Jun-dependent cellular senescence can be restored by activation of the epidermal growth factor receptor pathway. PMID- 20300112 TI - CAML regulates Bim-dependent thymocyte death. AB - Appropriate control of apoptosis during T lymphocyte differentiation is critical for destruction of T cells bearing potentially autoreactive or useless immuno receptors and for survival of those T cells bearing antigen receptors that may recognize foreign proteins. Despite the well-established importance of thymocyte survival, the exact signals regulating thymocyte apoptosis have not been fully elucidated. Here, we show that thymocytes lacking the endoplasmic reticulum protein calcium-modulating cyclophilin ligand (CAML) failed to undergo normal T cell development and exhibited dramatically increased rates of apoptosis. In vitro, CAML-deficient thymocytes accumulated high levels of reactive oxygen species (ROS) and underwent abnormally accelerated death in response to several cytotoxic stimuli, including treatment with etoposide, cytokine deprivation, or Fas ligation. Although neither p53 deletion nor loss of Fas rescued the survival and continued development of CAML-deficient thymocytes, removal of the pro apoptotic BH3-only Bcl-2 family member Bim significantly restored their survival. This work reveals CAML to be a critically important regulator of ROS- and Bim dependent thymocyte death. PMID- 20300114 TI - The numbers behind morphogenesis. AB - The IHES meeting on Pattern Formation in Morphogenesis covered computational approaches to understanding central developmental processes. Global changes in tissue morphogenesis were attributed to small local asymmetries in protein localization or activity, and the underlying mechanisms for robust patterning of defined signalling pathways were explored. PMID- 20300113 TI - Inhibition of Lck enhances glucocorticoid sensitivity and apoptosis in lymphoid cell lines and in chronic lymphocytic leukemia. AB - Glucocorticoids are used as part of front-line therapy to treat lymphoid malignancy because of their remarkable ability to induce apoptosis. Yet, in T cells, glucocorticoid-induced apoptosis is readily inhibited by lymphocyte activation and signaling. We have previously shown that the Src family kinase, Lck (lymphocyte cell-specific tyrosine kinase), which is predominantly expressed in T cells, interacts with IP3 receptors to facilitate calcium signaling. Here, we discovered that dexamethasone downregulates Lck, which, in turn, suppresses lymphocyte activation by inhibiting pro-survival calcium oscillations. Moreover, stable expression of shRNAs that selectively targeted Lck or treatment with the Src inhibitor dasatinib (BMS-354825) enhanced apoptosis induction by dexamethasone. To investigate the effect of Lck inhibition in a primary leukemia model, we employed chronic lymphocytic leukemia (CLL) cells that aberrantly expressed Lck and were relatively insensitive to dexamethasone. Lck expression was correlated with resistance to dexamethasone in CLL cells, and its inhibition by dasatinib or other inhibitors markedly enhanced glucocorticoid sensitivity. Collectively, these data indicate that Lck protects cells from glucocorticoid induced apoptosis and its inhibition enhances sensitivity to dexamethasone. Small molecule inhibitors of Lck, such as dasatinib, may function to reverse glucocorticoid resistance in some lymphoid malignancies. PMID- 20300115 TI - Metabolism and cancer mix in Madrid. AB - The CNIO Cancer Conference 'The Energy of Cancer' held last November was a bridge between metabolic and cancer research, emphasizing the interdisciplinary nature of the field. It confirmed that the outlines of the main pathways involved in coordinating nutrient uptake and metabolism with cell growth have begun to emerge. PMID- 20300116 TI - Zero sense in European approach to GM. PMID- 20300117 TI - Safeguarding good scientific practice in Europe. PMID- 20300119 TI - Conductin/axin2 and Wnt signalling regulates centrosome cohesion. AB - Activated Wnt/beta-catenin signalling is a characteristic of many cancers and drives cell-cycle progression. Here, we report a mechanism linking Wnt/beta catenin signalling to centrosome separation. We show that conductin/axin2, a negative regulator of beta-catenin, localizes at the centrosomes by binding to the centriole-associated component C-Nap1. Knockout or knockdown of conductin leads to premature centrosome separation--that is, splitting--which is abolished by knockdown of beta-catenin. Conductin promotes phosphorylation of the amino terminal serine (Ser 33/37) and threonine (Thr 41) residues of centrosome associated beta-catenin. Beta-catenin mutated at these residues causes centrosomal splitting, whereas a phospho-mimicking mutant of beta-catenin does not. Importantly, beta-catenin-induced splitting is not inhibited by blocking beta-catenin-dependent transcription. Treatment with Wnts and inhibition of glycogen synthase kinase 3 block beta-catenin phosphorylation and induce centrosomal splitting. These data indicate that Wnt/beta-catenin signalling and conductin regulate centrosomal cohesion by altering the phosphorylation status of beta-catenin at the centrosomes. PMID- 20300118 TI - Structural basis of wedging the Golgi membrane by FAPP pleckstrin homology domains. AB - The mechanisms underlying Golgi targeting and vesiculation are unknown, although the responsible phosphatidylinositol 4-phosphate (PtdIns(4)P) ligand and four phosphate-adaptor protein (FAPP) modules have been defined. The micelle-bound structure of the FAPP1 pleckstrin homology domain reveals how its prominent wedge independently tubulates Golgi membranes by leaflet penetration. Mutations compromising the exposed hydrophobicity of full-length FAPP2 abolish lipid monolayer binding and compression. The trafficking process begins with an electrostatic approach, phosphoinositide sampling and perpendicular penetration. Extensive protein contacts with PtdIns(4)P and neighbouring phospholipids reshape the bilayer and initiate tubulation through a conserved wedge with features shared by diverse protein modules. PMID- 20300120 TI - HLA and CTLA4 polymorphisms may confer a synergistic risk in the susceptibility to Graves' disease. AB - Graves' disease (GD) is an autoimmune disease characterized by hyperthyroidism due to the presence of autoantibodies against thyroid-stimulating hormone receptor, which is measured as thyroid-stimulating hormone-binding inhibitory immunoglobulin (TBII). Most of the GD patients are TBII-positive, but TBII is undetectable in a proportion of GD patients. We previously reported the association of HLA-A 02 and -DPB1 0501 with TBII-positive GD, whereas TBII negative GD showed association with HLA-A 02 and DPB1 0202. Recently, polymorphisms of cytotoxic T-lymphocyte-associated antigen-4 (CTLA4) gene are reported to be associated with GD. In this study, we investigated 329 (240 TBII positive and 89 TBII-negative) GD patients and 378 controls for the polymorphisms in HLA-A, -DPB1 and CTLA4 (CT60, rs3087243, A/G) to investigate the contribution of these factors in the susceptibility to GD. A significant association with CTLA4 was found for the TBII-positive GD (G carriers in patients vs controls, 97.1 vs 91.8%; odds ratio (OR)=2.97, 95% confidence interval=1.29-6.87, P=0.008), but the association was weak and not significant for the TBII-negative GD (94.4 vs 91.8%; OR=1.50, 95% confidence interval=0.57-3.98, P=0.41). Stratification analyses suggested a possible synergistic interaction of CTLA4 with HLA-A 02 and DPB1 0501 in the susceptibility to TBII-positive GD. PMID- 20300121 TI - Functional impact of a single-nucleotide polymorphism in the OPRD1 promoter region. AB - The delta-opioid receptor mediates rewarding effects of many substances of abuse. We reported an increased frequency of the minor G-allele of single-nucleotide polymorphism (SNP) rs569356 (the only variant identified so far in the promoter region of the delta-opioid receptor gene (OPRD1)) in subjects with opioid dependence. In this study, we examined the functional significance of this variant. OPRD1 promoter region harboring SNP rs569356 was amplified by PCR and inserted into a firefly luciferase reporter vector. HEK293 cells were co transfected with these constructs and a renilla luciferase vector to control for transfection efficiency. Expression of firefly luciferase (driven by the OPRD1 promoter) was measured by a dual luciferase reporter assay and normalized by renilla luciferase expression. Moreover, alleles altering expression were further assessed for binding of human brain nuclear proteins by electrophoretic mobility shift assay (EMSA). The minor G-allele was associated with significantly greater expression levels of firefly luciferase than the major A-allele of SNP rs569356 (P=0.003). EMSA also showed specific gel shift bands, suggesting that SNP rs569356 is situated in the binding site of potential transcription factors. These results suggest that the minor G-allele of SNP rs569356 may enhance transcription factor binding and increase OPRD1 expression. PMID- 20300122 TI - Are GJB2 mutations an aggravating factor in the phenotypic expression of mitochondrial non-syndromic deafness? AB - Hearing impairment is a frequent condition, and genes have an important role in its etiology. The majority of hearing loss occurs in non-syndromic form, with deafness being the only clinically recognizable feature. More than 60 nuclear genes or loci have been shown to be involved in non-syndromic hearing loss, but mutations in mitochondrial DNA also cause hearing impairment. Mitochondrial DNA mutations usually lead to progressive hearing loss with an age of onset varying from childhood to early adulthood. It is interesting to note that there is a great variability among phenotypes between individuals harboring the same mitochondrial mutation, even within the same family, and the phenotype may range from profound deafness to completely normal hearing. In the past years, the debate on mitochondrial mutations has been about the penetrance, the tissue specificity and the mechanisms of modifier genes that can modulate the severity of the phenotypic expression of the deafness-associated mitochondrial DNA mutations. Here we summarize evidence regarding modifying genes, and we discuss the effect of the coexistence of mitochondrial and GJB2 mutations in families reported to date. PMID- 20300123 TI - The pursuit of genome-wide association studies: where are we now? AB - It is now 5 years since the first genome-wide association studies (GWAS), published in 2005, identified a common risk allele with large effect size for age related macular degeneration in a small sample set. Following this exciting finding, researchers have become optimistic about the prospect of the genome-wide association approach. However, most of the risk alleles identified in the subsequent GWAS for various complex diseases are common with small effect sizes (odds ratio <1.5). So far, more than 450 GWAS have been published and the associations of greater than 2000 single nucleotide polymorphisms (SNPs) or genetic loci were reported. The aim of this review paper is to give an overview of the evolving field of GWAS, discuss the progress that has been made by GWAS and some of the interesting findings, and summarize what we have learned over the past 5 years about the genetic basis of human complex diseases. This review will focus on GWAS of SNPs association for complex diseases but not studies of copy number variations. PMID- 20300124 TI - Cerebral hemorrhage in Fabry's disease. AB - Fabry's disease is an X-linked lysosomal storage disorder resulting from alpha galactosidase A deficiency. Although ischemic stroke is recognized as an important manifestation of Fabry's disease, hemorrhagic stroke is considered to be rare. Here, we report our recent clinical experience with three hemizygous male patients with Fabry's disease who developed cerebral hemorrhage. One patient had classic type Fabry's disease with p.Ala37Val mutation and others had cerebrovascular variant with p.Glu66Gln mutation. Degeneration of the cerebral small arteries secondary to deposition of glycosphingolipids and aging, in addition to hypertension and antiplatelet/anticoagulant agents, are considered to be contributing factors for hemorrhage. Fabry's disease is frequently associated with not only ischemic but also hemorrhagic stroke, especially in elderly patients. PMID- 20300125 TI - Family-based association study of IGF1 microsatellites and height, weight, and body mass index. AB - Height, weight, and body mass index (BMI) are partly heritable, known to be associated with chronic diseases, and are linked to circulating insulin-like growth factor I (IGF-I) concentrations. IGF-I concentrations are also partly heritable and thus genetic variation at IGF1 could influence height, weight, BMI and the risk of developing chronic diseases. Our objective was to examine the association of genetic variation at IGF1 with height, weight and BMI using a sample of premenopausal women. A family-based study design was used to investigate the association of three IGF1 CA repeat variants at 5' (5'CA), intron 2 (In2CA) and 3' (3'CA) with these anthropometric measures. We analyzed the data for 827 families of different sizes and configurations, which included 1520 premenopausal women. Nominally significant associations (PX(2)Pi (0,0) electronic transition near 430 nm. The deposited diamond thin-films were characterized by scanning electron microscopy, stylus profilometry, and Raman spectroscopy. The deposition mechanism with and without the CO(2) laser excitation was discussed based on the OES spectral results. PMID- 20300151 TI - Laser optical gas sensor by photoexcitation effect on refractive index. AB - Laser optical gas sensors are fabricated by using the crystalline silicon carbide polytype 6H-SiC, which is a wide-bandgap semiconductor, and tested at high temperatures up to 650 degrees C. The sensor operates on the principle of semiconductor optics involving both the semiconductor and optical properties of the material. It is fabricated by doping 6H-SiC with an appropriate dopant such that the dopant energy level matches the quantum of energy of the characteristic radiation emitted by the combustion gas of interest. This radiation changes the electron density in the semiconductor by photoexcitation and, thereby, alters the refractive index of the sensor. The variation in the refractive index can be determined from an interference pattern. Such patterns are obtained for the reflected power of a He-Ne laser of wavelength 632.8 nm as a function of temperature. SiC sensors have been fabricated by doping two quadrants of a 6H-SiC chip with Ga and Al of dopant energy levels E(V)+0.29 eV and E(V)+0.23 eV, respectively. These doped regions exhibit distinct changes in the refractive index of SiC in the presence of carbon dioxide (CO(2)) and nitrogen monoxide (NO) gases respectively. Therefore Ga- and Al-doped 6H-SiC can be used for sensing CO(2) and NO gases at high temperatures, respectively. PMID- 20300152 TI - High-spatial-resolution nulling microellipsometer using rotational polarization symmetry. AB - We report the design and experimental testing of a high-spatial-resolution nulling microellipsometer. This microellipsometer design is based on the previously reported principle of rotational polarization symmetry to improve the signal-to-noise ratio of spatially resolved ellipsometric measurements. Through the use of an electro-optic polarization rotator, a null detection scheme is made possible and implemented. Surface profiling of a lithographically patterned microstructure is demonstrated with the nulling microellipsometer. A lateral spatial resolution of 0.48 microm is calculated with a numerical aperture of 0.9 and an illumination wavelength of 632.8 nm. PMID- 20300153 TI - Characterization of optical constants for uranium from 10 to 47 nm. AB - We use a laser high-harmonics-based extreme-ultraviolet (EUV) polarimeter to determine the optical constants of elemental uranium in the wavelength range from 10 to 47 nm. The constants are extracted from the measured ratio of p-polarized to s-polarized reflectance from a thin uranium film deposited in situ. The film thickness is inferred from a spectroscopic ellipsometry measurement of the sample after complete oxidation in room air. Uranium has been used as a high-reflectance material in the EUV. However, difficulties with oxidation prevented its careful characterization previous to this study. We find that measured optical constants for uranium vary significantly from previous estimates. PMID- 20300154 TI - Quantitative measurement of the phase locking of highly repetitive ultrashort optical pulses generated by a multifrequency continuous-wave Raman laser. AB - We proposed and demonstrated a novel method for the evaluation of optical pulse trains generated by a multifrequency continuous-wave Raman laser operating at a mode separation of 17.6 THz. This approach is based on the detection of a nonlinear signal arising from the intensity modulation of a pulse train, which should provide a useful means for measuring the deviation from phase locking of multifrequency lasers. Our results suggest that an optimization of intracavity dispersion allows the generation of phase-locked multifrequency emissions, which leads to optical pulse trains at a repetition rate in excess of 10 THz. PMID- 20300155 TI - Refractive index measurement using photonic crystal fiber-based Fabry-Perot interferometer. AB - We have constructed a novel refractive index (RI) sensor based on a fiber optic Fabry-Perot interferometer (FPI) by splicing a section of hollow core fiber between a single-mode fiber and a photonic crystal fiber (PCF). Owing to the air holes in the cladding of the PCF, various substances, such as liquids and gases with different RI, can enter or leave the in-fiber air cavity, which makes the device usable as a refractometer. In this paper, the fiber optic FPI sensor has been used to monitor the RI changes of air with different pressures, and the experimental results show that such a sensor has an RI sensitivity of 805.1 microm/RIU, and hysteresis is not observed. Moreover, the easy fabrication method gives the in-fiber refractometer many potential applications in the sensing field. PMID- 20300156 TI - Effect of fabrication errors on the diffraction pattern produced by sawtooth gratings. AB - In this work we investigate, analytically and numerically, the effect on the diffracted field produced by typical fabrication errors in sawtooth gratings. The analysis is carried out for the near and far field, showing the effects on the intensity and on the diffraction orders efficiency. When the grating profile is not perfect but presents a curved profile or overdevelopment error, some different diffraction orders appear, changing the intensity and the efficiency of each order. In addition, when roughness is present, a decreasing of efficiency is produced, but without generating different diffraction orders than the first one. We show the analytical dependence of these modifications in terms of the profile of the grating, corroborating the results with numerical methods. PMID- 20300157 TI - Effect of temperature on the molding of chalcogenide glass lenses for infrared imaging applications. AB - We examine the effect of temperature on the molding of chalcogenide glass for infrared (IR) lens fabrication and evaluate a molded chalcogenide glass lens. Both the adhesion of the chalcogenide glass to the mold's surface and lens breakage depended on the initial heating temperature and on the molding temperatures in the glass molding process. In addition, the molded chalcogenide glass lens was evaluated based on transcription characteristics of the mold's surface, IR transmittance, and x-ray diffraction patterns. From the analysis results, we verified that the chalcogenide glass lens for IR imaging application could be fabricated by well-controlled temperature conditions. PMID- 20300158 TI - Spectral anomaly detection in deep shadows. AB - Although several hyperspectral anomaly detection algorithms have proven useful when illumination conditions provide for enough light, many of these same detection algorithms fail to perform well when shadows are also present. To date, no general approach to the problem has been demonstrated. In this paper, a novel hyperspectral anomaly detection algorithm that adapts the dimensionality of the spectral detection subspace to multiple illumination levels is described. The novel detection algorithm is applied to reflectance domain hyperspectral data that represents a variety of illumination conditions: well illuminated and poorly illuminated (i.e., shadowed). Detection results obtained for objects located in deep shadows and light-shadow transition areas suggest superiority of the novel algorithm over standard subspace RX detection. PMID- 20300159 TI - Accommodating brightness and exposure levels in densitometry of stained polyacrylamide electrophoresis gels. AB - Flatbed scanner densitometers can be operated under various illumination and recording exposure levels. In this work, we show that optical density measurement accuracy, sensitivity, and stability of stained polyacrylamide electrophoresis gel densitometry are crucially dependent on these two factors (brightness and exposure level), notwithstanding that the source is monochromatic, spatially uniform, and the measurements are made using an accurately calibrated step wedge in tandem. We further outline a method to accommodate the intensity deviations over a range of illumination and exposure levels in order to maintain sensitivity and repeatability in the computed optical densities. Comparisons were also made with results from a commercial densitometer. PMID- 20300160 TI - Inversion of water cloud lidar signals based on accumulated depolarization ratio. AB - The relation between the accumulated single scattering factor and the layer accumulated depolarization ratio appears to be independent of the geometry of the measurements and contains information on the optical depth and thus on the extinction coefficient. A simple equation is developed to retrieve the extinction coefficient from the total integrated signal and the integrated depolarization ratio measurements. The results compare well with Klett and Weinman lidar inversion techniques. The results from the measurements of the integrated depolarization ratio can be used to set the far end initial extinction coefficient value required for Klett and Weinman lidar inversion or can be used directly. PMID- 20300161 TI - Simulation and experimental results of kaleidoscope homogenizers for longitudinal diode pumping. AB - With the goal to set a homogenizer to allow coupling of a stack of diodes with a disk amplifier medium for a longitudinally pumped laser or amplifier, we report simulation and experimental results on homogenization of the light supplied by a large stack of diodes. We investigate various kaleidoscope cross-section shapes and various optical coupling configurations. PMID- 20300162 TI - Evaluation and benchmarking of a pixel-shifting camera for superresolution lensless digital holography. AB - In lensless digital holography, the comparatively low resolution of the CCD devices that are used to record the digital holograms has to date limited both the maximum linear dimensions of the measurement object and also the minimum possible stand-off distance between the object and the CCD detector. A signal processing-based technique known as superresolution (SR) image reconstruction can provide an alternative approach that reduces these restrictions. We report on an SR image reconstruction technique that has been introduced by employing a camera with a "microscanning" function to capture SR digital holograms via multiple subpixel movements of the CCD sensor. A detailed description of the approach is given, along with experimental results, which are discussed and evaluated, showing the advantages of using this method. An approach using three-dimensional holographic contouring is also described that may be adopted as a strategy for benchmarking newly developed algorithms at any stage of the lensless digital holographic process. PMID- 20300163 TI - Characterization and reduction of reabsorption losses in luminescent solar concentrators. AB - The effects of excitation wavelength on the optical properties (emission spectrum and quantum yield) of a luminescent solar concentrator (LSC) containing a fluorescent organic dye (Lumogen F Rot 305) are studied. Excitation at wavelengths on the long-wavelength edge of the absorption spectrum of the dye results in redshifted emission, but the quantum yield remains constant at 100%. The origin of this effect and its consequences are discussed. The extent of the long-wavelength tail of the absorption spectrum of the dye is determined and the importance in reabsorption losses is shown. The optical efficiencies and photon transport probabilities of LSCs containing either an organic dye or a rare-earth lanthanide complex are compared using ray-tracing simulations and experiment. The optical efficiency is shown to depend strongly on the Stokes shift of the fluorophore. The lanthanide complex, which has a very large Stokes shift, exhibits a higher optical efficiency than the dye (64% cf. 50%), despite its lower quantum yield (86% cf. 100%). PMID- 20300164 TI - Impact of different Na-incorporating methods on Cu(In,Ga)Se2 thin film solar cells with a low-Na substrate. AB - As a kind of Na-incorporating control method, NaF co-evaporation or soda-lime glass thin films (SLGTFs) are useful to improve the photovoltaic performance of Cu(In,Ga)Se(2) (CIGS) cells fabricated on low-Na substrates. X-ray diffraction (XRD) patterns and scanning electron microscope pictures demonstrate that the grain size of CIGS thin film is reduced with the addition of Na. In addition, a variance of the preferred orientation is found by XRD patterns in terms of SLGTF samples. By a use of 100 nm thick SLGTF as a Na source, the best CIGS solar cell with an efficiency of 13.42% has been obtained. PMID- 20300165 TI - Generation of continuous-wave single-frequency 1.5 W 378 nm radiation by frequency doubling of a Ti:sapphire laser. AB - We have generated continuous-wave single-frequency 1.5 W 378 nm radiation by frequency doubling a high-power Ti:sapphire laser in an external enhancement cavity. An LBO crystal that is Brewster-cut and antireflection coated on both ends is used for a long-term stable frequency doubling. By optimizing the input coupler's reflectivity, we could generate 1.5 W 378 nm radiation from a 5 W 756 nm Ti:sapphire laser. According to our knowledge, this is the highest CW frequency-doubled power of a Ti:sapphire laser. PMID- 20300166 TI - Intense green upconversion emission in Tb3+/Yb3+ codoped alumino-germano-silicate optical fibers. AB - We observed intense green upconversion emission from Tb(3+) centered at 546 nm due to transition D(4)5-->F(5)7 in Tb(3+)/Yb(3+) codoped alumino-germano-silicate optical fibers by direct excitation of Yb(3+) ions with a laser diode at 976 nm. A two-photon cooperative energy transfer upconversion among a pair of Yb(3+) donor ions and a Tb(3+) acceptor ion are responsible for the observed green emission. Appropriately increasing the concentration of Tb(3+) relative to Yb(3+) was found to facilitate the energy transfer upconversion process from Yb(3+) to Tb(3+), while an excess of Tb(3+) ions inversely introduced more of the concentration quenching effect and phonon-assistant backward energy transfer from Tb(3+) to Yb(3+) and, therefore, damaged the observed green emission. The intensity of the observed green emission was found optimum for a concentration ratio of Tb(3+) to Yb(3+) of 2:1 in alumino-germano-silicate optical glass fibers. PMID- 20300167 TI - Demonstration of a 1.1 petawatt laser based on a hybrid optical parametric chirped pulse amplification/mixed Nd:glass amplifier. AB - We present the design and performance of the Texas Petawatt Laser, which produces a 186 J 167 fs pulse based on the combination of optical parametric chirped pulse amplification (OPCPA) and mixed Nd:glass amplification. OPCPA provides the majority of the gain and is used to broaden and shape the seed spectrum, while amplification in Nd:glass accounts for >99% of the final pulse energy. Compression is achieved with highly efficient multilayer dielectric gratings. PMID- 20300168 TI - Highly birefringent photonic crystal fiber based on a double-hole unit. AB - We propose a novel highly birefringent photonic crystal fiber (PCF) based on a double-hole unit. Because of the effect of the double-hole unit in which double airholes can be effectively viewed as elliptical airholes, the proposed PCF can achieve birefringence similar to that of an elliptical-hole PCF with high birefringence even up to the order of 0.01 and still avoid the inherent challenge to fabricate an elliptical-hole PCF. The proposed PCF also has a lower confinement loss than an elliptical-hole PCF with the same air-filling fraction. PMID- 20300170 TI - The worldwide airline network and the dispersal of exotic species: 2007-2010. AB - International air travel has played a significant role in driving recent increases in the rates of biological invasion and spread of infectious diseases. By providing high speed, busy transport links between spatially distant, but climatically similar regions of the world, the worldwide airline network (WAN) increases the risks of deliberate or accidental movements and establishment of climatically sensitive exotic organisms. With traffic levels continuing to rise and climates changing regionally, these risks will vary, both seasonally and year by-year. Here, detailed estimates of air traffic trends and climate changes for the period 2007-2010 are used to examine the likely directions and magnitudes of changes in climatically sensitive organism invasion risk across the WAN. Analysis of over 144 million flights from 2007-2010 shows that by 2010, the WAN is likely to change little overall in terms of connecting regions with similar climates, but anticipated increases in traffic and local variations in climatic changes should increase the risks of exotic species movement on the WAN and establishment in new areas. These overall shifts mask spatially and temporally heterogenous changes across the WAN, where, for example, traffic increases and climatic convergence by July 2010 between parts of China and northern Europe and North America raise the likelihood of exotic species invasions, whereas anticipated climatic shifts may actually reduce invasion risks into much of eastern Europe. PMID- 20300169 TI - Capillary electrophoresis mass spectrometry-based saliva metabolomics identified oral, breast and pancreatic cancer-specific profiles. AB - Saliva is a readily accessible and informative biofluid, making it ideal for the early detection of a wide range of diseases including cardiovascular, renal, and autoimmune diseases, viral and bacterial infections and, importantly, cancers. Saliva-based diagnostics, particularly those based on metabolomics technology, are emerging and offer a promising clinical strategy, characterizing the association between salivary analytes and a particular disease. Here, we conducted a comprehensive metabolite analysis of saliva samples obtained from 215 individuals (69 oral, 18 pancreatic and 30 breast cancer patients, 11 periodontal disease patients and 87 healthy controls) using capillary electrophoresis time-of flight mass spectrometry (CE-TOF-MS). We identified 57 principal metabolites that can be used to accurately predict the probability of being affected by each individual disease. Although small but significant correlations were found between the known patient characteristics and the quantified metabolites, the profiles manifested relatively higher concentrations of most of the metabolites detected in all three cancers in comparison with those in people with periodontal disease and control subjects. This suggests that cancer-specific signatures are embedded in saliva metabolites. Multiple logistic regression models yielded high area under the receiver-operating characteristic curves (AUCs) to discriminate healthy controls from each disease. The AUCs were 0.865 for oral cancer, 0.973 for breast cancer, 0.993 for pancreatic cancer, and 0.969 for periodontal diseases. The accuracy of the models was also high, with cross-validation AUCs of 0.810, 0.881, 0.994, and 0.954, respectively. Quantitative information for these 57 metabolites and their combinations enable us to predict disease susceptibility. These metabolites are promising biomarkers for medical screening. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s11306-009-0178-y) contains supplementary material, which is available to authorized users. PMID- 20300171 TI - Extreme female promiscuity in a non-social invertebrate species. AB - BACKGROUND: While males usually benefit from as many matings as possible, females often evolve various methods of resistance to matings. The prevalent explanation for this is that the cost of additional matings exceeds the benefits of receiving sperm from a large number of males. Here we demonstrate, however, a strongly deviating pattern of polyandry. METHODOLOGY/PRINCIPAL FINDINGS: We analysed paternity in the marine snail Littorina saxatilis by genotyping large clutches (53-79) of offspring from four females sampled in their natural habitats. We found evidence of extreme promiscuity with 15-23 males having sired the offspring of each female within the same mating period. CONCLUSIONS/SIGNIFICANCE: Such a high level of promiscuity has previously only been observed in a few species of social insects. We argue that genetic bet-hedging (as has been suggested earlier) is unlikely to explain such extreme polyandry. Instead we propose that these high levels are examples of convenience polyandry: females accept high numbers of matings if costs of refusing males are higher than costs of accepting superfluous matings. PMID- 20300172 TI - Genetic and epigenetic somatic alterations in head and neck squamous cell carcinomas are globally coordinated but not locally targeted. AB - BACKGROUND: Solid tumors, including head and neck squamous cell carcinomas (HNSCC), arise as a result of genetic and epigenetic alterations in a sustained stress environment. Little work has been done that simultaneously examines the spectrum of both types of changes in human tumors on a genome-wide scale and results so far have been limited and mixed. Since it has been hypothesized that epigenetic alterations may act by providing the second carcinogenic hit in gene silencing, we sought to identify genome-wide DNA copy number alterations and CpG dinucleotide methylation events and examine the global/local relationships between these types of alterations in HNSCC. METHODOLOGY/PRINCIPAL FINDINGS: We have extended a prior analysis of 1,413 cancer-associated loci for epigenetic changes in HNSCC by integrating DNA copy number alterations, measured at 500,000 polymorphic loci, in a case series of 19 primary HNSCC tumors. We have previously demonstrated that local copy number does not bias methylation measurements in this array platform. Importantly, we found that the global pattern of copy number alterations in these tumors was significantly associated with tumor methylation profiles (p<0.002). However at the local level, gene promoter regions did not exhibit a correlation between copy number and methylation (lowest q = 0.3), and the spectrum of genes affected by each type of alteration was unique. CONCLUSION/SIGNIFICANCE: This work, using a novel and robust statistical approach demonstrates that, although a "second hit" mechanism is not likely the predominant mode of action for epigenetic dysregulation in cancer, the patterns of methylation events are associated with the patterns of allele loss. Our work further highlights the utility of integrative genomics approaches in exploring the driving somatic alterations in solid tumors. PMID- 20300173 TI - Are maternal antibodies really that important? Patterns in the immunologic development of altricial passerine house sparrows (Passer domesticus). AB - BACKGROUND: Maternal antibodies are believed to play an integral role in protecting immunologically immature wild-passerines from environmental antigens. This study comprehensively examines the early development of the adaptive immune system in an altricial-developing wild passerine species, the house sparrow (Passer domestics), by characterizing the half-life of maternal antibodies in nestling plasma, the onset of de novo synthesis of endogenous antibodies by nestlings, and the timing of immunological independence, where nestlings rely entirely on their own antibodies for immunologic protection. METHODOLOGY/PRINCIPAL FINDINGS: In an aviary study we vaccinated females against a novel antigen that these birds would not otherwise encounter in their natural environment, and measured both antigen-specific and total antibody concentration in the plasma of females, yolks, and nestlings. We traced the transfer of maternal antibodies from females to nestlings through the yolk and measured catabolisation of maternal antigen-specific antibodies in nestlings during early development. By utilizing measurements of non-specific and specific antibody levels in nestling plasma we were able to calculate the half-life of maternal antibodies in nestling plasma and the time point at which nestling were capable of synthesizing antibodies themselves. Based on the short half-life of maternal antibodies, the rapid production of endogenous antibodies by nestlings and the relatively low transfer of maternal antibodies to nestlings, our findings suggest that altricial-developing sparrows achieve immunologic independence much earlier than precocial birds. CONCLUSIONS/SIGNIFICANCE: To our knowledge, this is the first in depth analyses performed on the adaptive immune system of a wild passerine species. Our results suggest that maternal antibodies may not confer the immunologic protection or immune priming previously proposed in other passerine studies. Further research needs to be conducted on other altricial passerines to determine if the results of our study are a species-specific phenomenon or if they apply to all altricial-developing birds. PMID- 20300174 TI - Record dynamics in ants. AB - The success of social animals (including ourselves) can be attributed to efficiencies that arise from a division of labour. Many animal societies have a communal nest which certain individuals must leave to perform external tasks, for example foraging or patrolling. Staying at home to care for young or leaving to find food is one of the most fundamental divisions of labour. It is also often a choice between safety and danger. Here we explore the regulation of departures from ant nests. We consider the extreme situation in which no one returns and show experimentally that exiting decisions seem to be governed by fluctuating record signals and ant-ant interactions. A record signal is a new 'high water mark' in the history of a system. An ant exiting the nest only when the record signal reaches a level it has never perceived before could be a very effective mechanism to postpone, until the last possible moment, a potentially fatal decision. We also show that record dynamics may be involved in first exits by individually tagged ants even when their nest mates are allowed to re-enter the nest. So record dynamics may play a role in allocating individuals to tasks, both in emergencies and in everyday life. The dynamics of several complex but purely physical systems are also based on record signals but this is the first time they have been experimentally shown in a biological system. PMID- 20300176 TI - Variation in DNA substitution rates among lineages erroneously inferred from simulated clock-like data. AB - BACKGROUND: The observation of variation in substitution rates among lineages has led to (1) a general rejection of the molecular clock model, and (2) the suggestion that a number of biological characteristics of organisms can cause rate variation. Accurate estimates of rate variation, and thus accurate inferences regarding the causes of rate variation, depend on accurate estimates of substitution rates. However, theory suggests that even when the substitution process is clock-like, variable numbers of substitutions can occur among lineages because the substitution process is stochastic. Furthermore, substitution rates along lineages can be misestimated, particularly when multiple substitutions occur at some sites. Although these potential causes of error in rate estimation are well understood in theory, such error has not been examined in detail; consequently, empirical studies that estimate rate variation among lineages have been unable to determine whether their results could be impacted by estimation error. METHODOLOGY/PRINCIPAL FINDINGS: To evaluate the extent to which error in rate estimation could erroneously suggest rate variation among lineages, we examined rate variation estimated for datasets simulated under a molecular clock on trees with equal and variable branch lengths. Thus, any apparent rate variation in these datasets reflects error in rate estimation rather than true differences in the underlying substitution process. We observed substantial rate variation among lineages in our simulations; however, we did not observe rate variation when average substitution rates were compared between different clades. CONCLUSIONS/SIGNIFICANCE: Our results confirm previous theoretical work suggesting that observations of among lineage rate variation in empirical data may be due to the stochastic substitution process and error in the estimation of substitution rates, rather than true differences in the underlying substitution process among lineages. However, conclusions regarding rate variation drawn from rates averaged across multiple branches are likely due to real, systematic variation in rates between groups. PMID- 20300175 TI - Predicting drug-target interaction networks based on functional groups and biological features. AB - BACKGROUND: Study of drug-target interaction networks is an important topic for drug development. It is both time-consuming and costly to determine compound protein interactions or potential drug-target interactions by experiments alone. As a complement, the in silico prediction methods can provide us with very useful information in a timely manner. METHODS/PRINCIPAL FINDINGS: To realize this, drug compounds are encoded with functional groups and proteins encoded by biological features including biochemical and physicochemical properties. The optimal feature selection procedures are adopted by means of the mRMR (Maximum Relevance Minimum Redundancy) method. Instead of classifying the proteins as a whole family, target proteins are divided into four groups: enzymes, ion channels, G protein- coupled receptors and nuclear receptors. Thus, four independent predictors are established using the Nearest Neighbor algorithm as their operation engine, with each to predict the interactions between drugs and one of the four protein groups. As a result, the overall success rates by the jackknife cross-validation tests achieved with the four predictors are 85.48%, 80.78%, 78.49%, and 85.66%, respectively. CONCLUSION/SIGNIFICANCE: Our results indicate that the network prediction system thus established is quite promising and encouraging. PMID- 20300177 TI - BOLD signal in both ipsilateral and contralateral retinotopic cortex modulates with perceptual fading. AB - Under conditions of visual fixation, perceptual fading occurs when a stationary object, though present in the world and continually casting light upon the retina, vanishes from visual consciousness. The neural correlates of the consciousness of such an object will presumably modulate in activity with the onset and cessation of perceptual fading. METHOD: In order to localize the neural correlates of perceptual fading, a green disk that had been individually set to be equiluminant with the orange background, was presented in one of the four visual quadrants; Subjects indicated with a button press whether or not the disk was subjectively visible as it perceptually faded in and out. RESULTS: Blood oxygen-level dependent (BOLD) signal in V1 and ventral retinotopic areas V2v and V3v decreases when the disk subjectively disappears, and increases when it subjectively reappears. This effect occurs in early visual areas both ipsilaterally and contralaterally to the fading figure. That is, it occurs regardless of whether the fading stimulus is presented inside or outside of the corresponding portion of visual field. In addition, we find that the microsaccade rate rises before and after perceptual transitions from not seeing to seeing the disk, and decreases before perceptual transitions from seeing to not seeing the disk. These BOLD signal changes could be driven by a global process that operates across contralateral and ipsilateral visual cortex or by a confounding factor, such as microsaccade rate. PMID- 20300178 TI - A novel translocation breakpoint within the BPTF gene is associated with a pre malignant phenotype. AB - Partial gain of chromosome arm 17q is an abundant aberrancy in various cancer types such as lung and prostate cancer with a prominent occurrence and prognostic significance in neuroblastoma--one of the most common embryonic tumors. The specific genetic element/s in 17q responsible for the cancer-promoting effect of these aberrancies is yet to be defined although many genes located in 17q have been proposed to play a role in malignancy. We report here the characterization of a naturally-occurring, non-reciprocal translocation der(X)t(X;17) in human lung embryonal-derived cells following continuous culturing. This aberrancy was strongly correlated with an increased proliferative capacity and with an acquired ability to form colonies in vitro. The breakpoint region was mapped by fluorescence in situ hybridization (FISH) to the 17q24.3 locus. Further characterization by a custom-made comparative genome hybridization array (CGH) localized the breakpoint within the Bromodomain PHD finger Transcription Factor gene (BPTF), a gene involved in transcriptional regulation and chromatin remodeling. Interestingly, this translocation led to elevation in the mRNA levels of the endogenous BPTF. Knock-down of BPTF restricted proliferation suggesting a role for BPTF in promoting cellular growth. Furthermore, the BPTF chromosomal region was found to be amplified in various human tumors, especially in neuroblastomas and lung cancers in which 55% and 27% of the samples showed gain of 17q24.3, respectively. Additionally, 42% percent of the cancer cell lines comprising the NCI-60 had an abnormal BPTF locus copy number. We suggest that deregulation of BPTF resulting from the translocation may confer the cells with the observed cancer-promoting phenotype and that our cellular model can serve to establish causality between 17q aberrations and carcinogenesis. PMID- 20300179 TI - Immune requirements of post-exposure immunization with modified vaccinia Ankara of lethally infected mice. AB - Current prophylactic vaccines work via the induction of B and T cell mediated memory that effectively control further replication of the pathogen after entry. In the case of therapeutic or post-exposure vaccinations the situation is far more complex, because the pathogen has time to establish itself in the host, start producing immune-inhibitory molecules and spread into distant organs. So far it is unclear which immune parameters have to be activated in order to thwart an existing lethal infection. Using the mousepox model, we investigated the immunological mechanisms responsible for a successful post-exposure immunization with modified vaccinia Ankara (MVA). In contrast to intranasal application of MVA, we found that intravenous immunization fully protected mice infected with ectromelia virus (ECTV) when applied three days after infection. Intravenous MVA immunization induced strong innate and adaptive immune responses in lethally infected mice. By using various gene-targeted and transgenic mouse strains we show that NK cells, CD4 T cells, CD8 T cells and antibodies are essential for the clearance of ECTV after post-exposure immunization. Post-exposure immunization with MVA is an effective measure in a murine model of human smallpox. MVA activates innate and adaptive immune parameters and only a combination thereof is able to purge ECTV from its host. These data not only provide a basis for therapeutic vaccinations in the case of the deliberate release of pathogenic poxviruses but possibly also for the treatment of chronic infections and cancer. PMID- 20300180 TI - The extracytoplasmic function sigma factor SigV plays a key role in the original model of lysozyme resistance and virulence of Enterococcus faecalis. AB - BACKGROUND: Enterococcus faecalis is one of the leading agents of nosocomial infections. To cause diseases, pathogens or opportunistic bacteria have to adapt and survive to the defense systems encountered in the host. One of the most important compounds of the host innate defense response against invading microorganisms is lysozyme. It is found in a wide variety of body fluids, as well as in cells of the innate immune system. Lysozyme could act either as a muramidase and/or as a cationic antimicrobial peptide. Like Staphylococcus aureus, E. faecalis is one of the few bacteria that are completely lysozyme resistant. RESULTS: This study revealed that oatA (O-acetyl transferase) and dlt (D-Alanylation of lipoteicoic acids) genes contribute only partly to the lysozyme resistance of E. faecalis and that a specific transcriptional regulator, the extracytoplasmic function SigV sigma factor plays a key role in this event. Indeed, the sigV single mutant is as sensitive as the oatA/dltA double mutant, and the sigV/oatA/dltA triple mutant displays the highest level of lysozyme sensitivity suggesting synergistic effects of these genes. In S. aureus, mutation of both oatA and dlt genes abolishes completely the lysozyme resistance, whereas this is not the case in E. faecalis. Interestingly SigV does not control neither oatA nor dlt genes. Moreover, the sigV mutants clearly showed a reduced capacity to colonize host tissues, as they are significantly less recovered than the parental JH2-2 strain from organs of mice subjected to intravenous or urinary tract infections. CONCLUSIONS: This work led to the discovery of an original model of lysozyme resistance mechanism which is obviously more complex than those described for other Gram positive pathogens. Moreover, our data provide evidences for a direct link between lysozyme resistance and virulence of E. faecalis. PMID- 20300181 TI - Interaction of E2 glycoprotein with heparan sulfate is crucial for cellular infection of Sindbis virus. AB - Cell culture-adapted strains of Sindbis virus (SINV) initially attach to cells by the ability to interact with heparan sulfate (HS) through selective mutation for positively charged amino acid (aa) scattered in E2 glycoprotein (W. B. Klimstra, K. D. Ryman, and R. E. Johnston, J. Virol. 72: 7357-7366, 1998). Here we have further confirmed that interaction of E2 protein with HS is crucial for cellular infection of SINV based on the reverse genetic system of XJ-160 virus, a Sindbis like virus (SINLV). Both SINV YN87448 and SINLV XJ-160 displayed similar infectivity on BHK-21, Vero, or C6/36 cells, but XJ-160 failed to infect mouse embryonic fibroblast (MEF) cells. The molecular mechanisms underlying the selective infectivity of XJ-160 were approached by substituting the E1, E2, or both genes of XJ-160 with that of YN87448, and the chimeric virus was denominated as XJ-160/E1, XJ-160/E2, or XJ-160/E1E2, respectively. In contrast to the parental XJ-160, all chimeric viruses became infectious to wild-type MEF cells (MEF-wt). While MEF-Ext(-/-) cells, producing shortened HS chains, were resistant not only to XJ-160, but also to YN87448 as well as the chimeric viruses, indicating that the inability of XJ-160 to infect MEF-wt cells likely due to its incompetent discrimination of cellular HS. Treatment with heparin or HS-degrading enzyme resulted in a substantial decrease in plaque formation by YN87448, XJ 160/E2, and XJ-160/E1E2, but had marginal effect on XJ-160 and XJ-160/E1, suggesting that E2 glycoprotein from YN87448 plays a more important role than does E1 in mediating cellular HS-related cell infection. In addition, the peptide containing 145-150 aa from E2 gene of YN87448 specifically bound to heparin, while the corresponding peptide from the E2 gene of XJ-160 essentially showed no binding to heparin. As a new dataset, these results clearly confirm an essential role of E2 glycoprotein, especially the domain of 145-150 aa, in SINV cellular infection through the interaction with HS. PMID- 20300182 TI - Plasmid construction using recombination activity in the fission yeast Schizosaccharomyces pombe. AB - BACKGROUND: Construction of plasmids is crucial in modern genetic manipulation. As of now, the common method for constructing plasmids is to digest specific DNA sequences with restriction enzymes and to ligate the resulting DNA fragments with DNA ligase. Another potent method to construct plasmids, known as gap-repair cloning (GRC), is commonly used in the budding yeast Saccharomyces cerevisiae. GRC makes use of the homologous recombination activity that occurs within the yeast cells. Due to its flexible design and efficiency, GRC has been frequently used for constructing plasmids with complex structures as well as genome-wide plasmid collections. Although there have been reports indicating GRC feasibility in the fission yeast Schizosaccharomyces pombe, this species is not commonly used for GRC as systematic studies of reporting GRC efficiency in S. pombe have not been performed till date. METHODOLOGY/PRINCIPAL FINDINGS: We investigated GRC efficiency in S. pombe in this study. We first showed that GRC was feasible in S. pombe by constructing a plasmid that contained the LEU2 auxotrophic marker gene in vivo and showed sufficient efficiency with short homology sequences (>25 bp). No preference was shown for the sequence length from the cut site in the vector plasmid. We next showed that plasmids could be constructed in a proper way using 3 DNA fragments with 70% efficiency without any specific selections being made. The GRC efficiency with 3 DNA fragments was dramatically increased >95% in lig4Delta mutant cell, where non-homologous end joining is deficient. Following this approach, we successfully constructed plasmid vectors with leu1+, ade6+, his5+, and lys1+ markers with the low-copy stable plasmid pDblet as a backbone by applying GRC in S. pombe. CONCLUSIONS/SIGNIFICANCE: We concluded that GRC was sufficiently feasible in S. pombe for genome-wide gene functional analysis as well as for regular plasmid construction. Plasmids with different markers constructed in this research are available from NBRP-yeast (http://yeast.lab.nig.ac.jp/). PMID- 20300183 TI - Does plasminogen activator inhibitor-1 drive lymphangiogenesis? AB - The purpose of this study is to explore the function of plasminogen activator inhibitor-1 (PAI-1) during pathological lymphangiogenesis. PAI-1, the main physiological inhibitor of plasminogen activators is involved in pathological angiogenesis at least by controlling extracellular proteolysis and by regulating endothelial cell survival and migration. Protease system's role in lymphangiogenesis is unknown yet. Thus, based on its important pro-angiogenic effect, we hypothesized that PAI-1 may regulate lymphangiogenesis associated at least with metastatic dissemination of cancer cells. To address this issue, we studied the impact of PAI-1 deficiency in various murine models of tumoral lymphangiogenesis. Wild-type PAI-1 proficient mice were used as controls. We provide for the first time evidence that PAI-1 is dispensable for tumoral lymphangiogenesis associated with breast cancers either induced by mammary carcinoma cell injection or spontaneously appearing in transgenic mice expressing the polyomavirus middle T antigen (PymT) under the control of a mouse mammary tumor virus long-terminal repeat promoter (MMTV-LTR). We also investigated inflammation-related lymphatic vessel recruitment by using two inflammatory models. PAI-1 deficiency did neither affect the development of lymphangioma nor burn-induced corneal lymphangiogenesis. These novel data suggest that vascular remodelling associated with lymphangiogenesis and angiogenesis involve different molecular determinants. PAI-1 does not appear as a potential therapeutic target to counteract pathological lymphangiogenesis. PMID- 20300185 TI - Integrative pathway-centric modeling of ventricular dysfunction after myocardial infarction. AB - BACKGROUND: A significant proportion of myocardial infarction (MI) patients undergo complex, coordinated perturbations at the molecular level that may eventually drive the occurrence of ventricular dysfunction and heart failure. Despite advances in the elucidation of key processes implicated in this condition, traditional methods relying on gene expression data and the identification of individual biomarkers in isolation pose major limitations not only for improving prediction power, but also for model interpretability. Mechanisms underlying clinical responses after MI remain elusive and there is no biomarker with the capacity to accurately predict ventricular dysfunction after MI. This calls for the exploration of system-level modeling of ventricular dysfunction in post-MI patients. Within this discovery framework key perturbations and predictive patterns are characterized by the integrated biological activity levels observed in pathways, rather than in individual genes. METHODOLOGY/PRINCIPAL FINDINGS: Here we report an integrative approach to identifying pathways related with ventricular dysfunction post MI with potential prognostic and therapeutic value. We found that a diversity of pathway-level perturbations can be profiled in samples of patients with ventricular dysfunction post MI, most of which represent major reductions of gene expression. Highly perturbed pathways included those implicated in antigen-dependent B-cell activation and the synthesis of leucine. By analyzing patient-specific samples encoded with information derived from highly-perturbed pathways, it is possible to visualize differential prognostic patterns and to perform computational classification of patients with areas under the receiver operating characteristic curve above 0.75. We also demonstrate how the integration of the outcomes generated by different pathway-based analysis models may improve ventricular dysfunction prediction performance. SIGNIFICANCE: This research offers an alternative, comprehensive view of key relationships and perturbations that may trigger the emergence or prevention of ventricular dysfunction post-MI. PMID- 20300184 TI - Motor neuron synapse and axon defects in a C. elegans alpha-tubulin mutant. AB - Regulation of microtubule dynamics underlies many fundamental cellular mechanisms including cell division, cell motility, and transport. In neurons, microtubules play key roles in cell migration, axon outgrowth, control of axon and synapse growth, and the regulated transport of vesicles and structural components of synapses. Loss of synapse and axon integrity and disruption of axon transport characterize many neurodegenerative diseases. Recently, mutations that specifically alter the assembly or stability of microtubules have been found to directly cause neurodevelopmental defects or neurodegeneration in vertebrates. We report here the characterization of a missense mutation in the C-terminal domain of C. elegans alpha-tubulin, tba-1(ju89), that disrupts motor neuron synapse and axon development. Mutant ju89 animals exhibit reduction in the number and size of neuromuscular synapses, altered locomotion, and defects in axon extension. Although null mutations of tba-1 show a nearly wild-type pattern, similar axon outgrowth defects were observed in animals lacking the beta-tubulin TBB-2. Genetic analysis reveals that tba-1(ju89) affects synapse development independent of its role in axon outgrowth. tba-1(ju89) is an altered function allele that most likely perturbs interactions between TBA-1 and specific microtubule associated proteins that control microtubule dynamics and transport of components needed for synapse and axon growth. PMID- 20300186 TI - Literature review comparing laparoscopic and percutaneous endoscopic gastrostomies in a pediatric population. AB - Objective. This study compares laparoscopic and percutaneous endoscopic gastrostomy (PEG) in a paediatric population to test the hypothesis that there is a difference in the frequency of serious gastrointestinal complications between the two methods. Methods. All reports published between 1995 and 2009 on laparoscopic gastrostomy and PEG in children was included. Prospective and retrospective trials, comparing the two methods or dealing with one of them only were included. Endpoints were accidentally performed gastrointestinal fistula causing an emergency re-operation. The frequency of inadvertent gastroenteric fistulas using the two different techniques was calculated. Results. 822 publications were found when using the search terms: gastrostomy, gastrointestinal complications, and all child: 0-18 years. From these, 54 studies were extracted for this investigation. These studies reported a total of 4331 children undergoing gastrostomy operation, 1027 by using the laparoscopic technique and 3304 using the PEG technique. The number of serious gastrointestinal fistulas to colon or small bowel was 0% and .27%, respectively, P < .05. Conclusions. The results suggest that by performing laparoscopic gastrostomy in children it is possible to avoid the serious intestinal fistula complications caused by a blind puncture through the abdominal cavity when performing the PEG. PMID- 20300187 TI - Correlation between clinicopathology and expression of heat shock protein 72 and glycoprotein 96 in human esophageal squamous cell carcinoma. AB - Heat shock protein 72 (HSP72) and glycoprotein 96 (gp96) are highly expressed in cancer tissues. Recent studies indicate the possible roles of HSP72 and gp96 in the development and progression of gastrointestinal carcinomas but detailed information is still ambiguous. We investigated the correlation between clinicopathology and expression of HSP72 and gp96 in human esophageal squamous cell carcinoma. The expression of HSP72 and gp96 was studied in 120 human esophageal squamous cell carcinomas with or without metastasis as well as in mucous membrane adjacent to cancers by way of immunohistochemistry. HSP72 immunoreactivities were detected in 112 of 120 primary tumors (93.3%) and in 30 of 120 mucous membranes adjacent to cancers (25.0%). Gp96 detected in esophageal squamous cell carcinoma and inmucous membrane adjacent to cancer was 85.0% and 20.0%, respectively. Both HSP72 and gp96 stained in cytoplasm. HSP72 and gp96 expression in esophageal squamous cell carcinomas with metastasis was significantly higher than those with nonmetastasis (P < .05). The results indicate that there exists a significant correlation between the expression of HSP72 and gp96 and the progression of esophageal squamous cell carcinomas. HSP72 and gp96 expression were significantly associated with the presence of tumor infiltration, lymph node, and remote metastasis. PMID- 20300188 TI - Spontaneous tumor lysis syndrome in the setting of B-cell lymphoma. AB - Tumor lysis syndrome (TLS) presenting in absence of chemotherapy is a rare occurrence. One of the true oncological emergencies, it can lead to significant morbidity and mortality. TLS is a phenomena usually associated with tumor cell death after treatment. The etiology of the spontaneous TLS is not well understood, which complicates the diagnosis. TLS is well known to oncologists but physicians outside of this specialty have little or no experience with this condition. Early recognition and treatment are the keys to limiting the sequela of the condition. Spontaneous tumor lysis syndrome is rare but presents added risks to the patient because of the potential for delayed diagnosis and no benefit of pretreatment. Diagnosis may be further delayed because this may be the first symptom of underlying malignancy. Therefore, it is imperative that all clinicians are familiar with the syndrome to assure timely recognition. PMID- 20300190 TI - Characterization of the Melanoma miRNAome by Deep Sequencing. AB - BACKGROUND: MicroRNAs (miRNAs) are 18-23 nucleotide non-coding RNAs that regulate gene expression in a sequence specific manner. Little is known about the repertoire and function of miRNAs in melanoma or the melanocytic lineage. We therefore undertook a comprehensive analysis of the miRNAome in a diverse range of pigment cells including: melanoblasts, melanocytes, congenital nevocytes, acral, mucosal, cutaneous and uveal melanoma cells. METHODOLOGY/PRINCIPAL FINDINGS: We sequenced 12 small RNA libraries using Illumina's Genome Analyzer II platform. This massively parallel sequencing approach of a diverse set of melanoma and pigment cell libraries revealed a total of 539 known mature and mature-star sequences, along with the prediction of 279 novel miRNA candidates, of which 109 were common to 2 or more libraries and 3 were present in all libraries. CONCLUSIONS/SIGNIFICANCE: Some of the novel candidate miRNAs may be specific to the melanocytic lineage and as such could be used as biomarkers to assist in the early detection of distant metastases by measuring the circulating levels in blood. Follow up studies of the functional roles of these pigment cell miRNAs and the identification of the targets should shed further light on the development and progression of melanoma. PMID- 20300191 TI - Tgf-Beta isoform specific regulation of airway inflammation and remodelling in a murine model of asthma. AB - The TGF-beta family of mediators are thought to play important roles in the regulation of inflammation and airway remodelling in asthma. All three mammalian isoforms of TGF-beta, TGF-beta(1-3), are expressed in the airways and TGF-beta(1) and -beta(2) are increased in asthma. However, there is little information on the specific roles of individual TGF-beta isoforms. In this study we assess the roles of TGF-beta(1) and TGF-beta(2) in the regulation of allergen-induced airway inflammation and remodelling associated with asthma, using a validated murine model of ovalbumin sensitization and challenge, and isoform specific TGF-beta neutralising antibodies. Antibodies to both isoforms inhibited TGF-beta mediated Smad signalling. Anti-TGF-beta(1) and anti-TGF-beta(2) inhibited ovalbumin induced sub-epithelial collagen deposition but anti-TGF-beta(1) also specifically regulated airway and fibroblast decorin deposition by TGF-beta(1). Neither antibody affected the allergen-induced increase in sub-epithelial fibroblast-like cells. Anti- TGF-beta(1) also specifically inhibited ovalbumin-induced increases in monocyte/macrophage recruitment. Whereas, both TGF-beta(1) and TGF-beta(2) were involved in regulating allergen-induced increases in eosinophil and lymphocyte numbers. These data show that TGF-beta(1) and TGF-beta(2) exhibit a combination of specific and shared roles in the regulation of allergen-induced airway inflammation and remodelling. They also provide evidence in support of the potential for therapeutic regulation of specific subsets of cells and extracellular matrix proteins associated with inflammation and remodelling in airway diseases such as asthma and COPD, as well as other fibroproliferative diseases. PMID- 20300192 TI - Microenvironment modulates osteogenic cell lineage commitment in differentiated embryonic stem cells. AB - BACKGROUND: Due to their self-renewal, embryonic stem cells (ESCs) are attractive cells for applications in regenerative medicine and tissue engineering. Although ESC differentiation has been used as a platform for generating bone in vitro and in vivo, the results have been unsatisfactory at best. It is possible that the traditional culture methods, which have been used, are not optimal and that other approaches must be explored. METHODOLOGY/PRINCIPAL FINDINGS: ESCs were differentiated into osteoblast lineage using a micro-mass approach. In response to osteogenic differentiation medium, many cells underwent apoptosis, while others left the micro-mass, forming small aggregates in suspension. These aggregates were cultured in three different culture conditions (adhesion, static suspension, and stirred suspension), then examined for osteogenic potential in vitro and in vivo. In adhesion culture, ESCs primed to become osteoblasts recommitted to the adipocyte lineage in vitro. In a static suspension culture, resulting porous aggregates expressed osteoblasts markers and formed bone in vivo via intermembranous ossification. In a stirred suspension culture, resulting non porous aggregates suppressed osteoblast differentiation in favor of expanding progenitor cells. CONCLUSIONS/SIGNIFICANCE: We demonstrate that microenvironment modulates cell fate and subsequent tissue formation during ESC differentiation. For effective tissue engineering using ESCs, it is important to develop optimized cell culture/differentiation conditions based upon the influence of microenvironment. PMID- 20300193 TI - Purification and functional characterisation of rhinocerase, a novel serine protease from the venom of Bitis gabonica rhinoceros. AB - BACKGROUND: Serine proteases are a major component of viper venoms and are thought to disrupt several distinct elements of the blood coagulation system of envenomed victims. A detailed understanding of the functions of these enzymes is important both for acquiring a fuller understanding of the pathology of envenoming and because these venom proteins have shown potential in treating blood coagulation disorders. METHODOLOGY/PRINCIPAL FINDINGS: In this study a novel, highly abundant serine protease, which we have named rhinocerase, has been isolated and characterised from the venom of Bitis gabonica rhinoceros using liquid phase isoelectric focusing and gel filtration. Like many viper venom serine proteases, this enzyme is glycosylated; the estimated molecular mass of the native enzyme is approximately 36 kDa, which reduces to 31 kDa after deglycosylation. The partial amino acid sequence shows similarity to other viper venom serine proteases, but is clearly distinct from the sequence of the only other sequenced serine protease from Bitis gabonica. Other viper venom serine proteases have been shown to exert distinct biological effects, and our preliminary functional characterization of rhinocerase suggest it to be multifunctional. It is capable of degrading alpha and beta chains of fibrinogen, dissolving plasma clots and of hydrolysing a kallikrein substrate. CONCLUSIONS/SIGNIFICANCE: A novel multifunctional viper venom serine protease has been isolated and characterised. The activities of the enzyme are consistent with the known in vivo effects of Bitis gabonica envenoming, including bleeding disorders, clotting disorders and hypotension. This study will form the basis for future research to understand the mechanisms of serine protease action, and examine the potential for rhinocerase to be used clinically to reduce the risk of human haemostatic disorders such as heart attacks and strokes. PMID- 20300194 TI - BTG interacts with retinoblastoma to control cell fate in Dictyostelium. AB - BACKGROUND: In the genesis of many tissues, a phase of cell proliferation is followed by cell cycle exit and terminal differentiation. The latter two processes overlap: genes involved in the cessation of growth may also be important in triggering differentiation. Though conceptually distinct, they are often causally related and functional interactions between the cell cycle machinery and cell fate control networks are fundamental to coordinate growth and differentiation. A switch from proliferation to differentiation may also be important in the life cycle of single-celled organisms, and genes which arose as regulators of microbial differentiation may be conserved in higher organisms. Studies in microorganisms may thus contribute to understanding the molecular links between cell cycle machinery and the determination of cell fate choice networks. METHODOLOGY/PRINCIPAL FINDINGS: Here we show that in the amoebozoan D. discoideum, an ortholog of the metazoan antiproliferative gene btg controls cell fate, and that this function is dependent on the presence of a second tumor suppressor ortholog, the retinoblastoma-like gene product. Specifically, we find that btg-overexpressing cells preferentially adopt a stalk cell (and, more particularly, an Anterior-Like Cell) fate. No btg-dependent preference for ALC fate is observed in cells in which the retinoblastoma-like gene has been genetically inactivated. Dictyostelium btg is the only example of non-metazoan member of the BTG family characterized so far, suggesting that a genetic interaction between btg and Rb predated the divergence between dictyostelids and metazoa. CONCLUSIONS/SIGNIFICANCE: While the requirement for retinoblastoma function for BTG antiproliferative activity in metazoans is known, an interaction of these genes in the control of cell fate has not been previously documented. Involvement of a single pathway in the control of mutually exclusive processes may have relevant implication in the evolution of multicellularity. PMID- 20300196 TI - Plant species and functional group combinations affect green roof ecosystem functions. AB - BACKGROUND: Green roofs perform ecosystem services such as summer roof temperature reduction and stormwater capture that directly contribute to lower building energy use and potential economic savings. These services are in turn related to ecosystem functions performed by the vegetation layer such as radiation reflection and transpiration, but little work has examined the role of plant species composition and diversity in improving these functions. METHODOLOGY/PRINCIPAL FINDINGS: We used a replicated modular extensive (shallow growing- medium) green roof system planted with monocultures or mixtures containing one, three or five life-forms, to quantify two ecosystem services: summer roof cooling and water capture. We also measured the related ecosystem properties/processes of albedo, evapotranspiration, and the mean and temporal variability of aboveground biomass over four months. Mixtures containing three or five life-form groups, simultaneously optimized several green roof ecosystem functions, outperforming monocultures and single life-form groups, but there was much variation in performance depending on which life-forms were present in the three life-form mixtures. Some mixtures outperformed the best monocultures for water capture, evapotranspiration, and an index combining both water capture and temperature reductions. Combinations of tall forbs, grasses and succulents simultaneously optimized a range of ecosystem performance measures, thus the main benefit of including all three groups was not to maximize any single process but to perform a variety of functions well. CONCLUSIONS/SIGNIFICANCE: Ecosystem services from green roofs can be improved by planting certain life-form groups in combination, directly contributing to climate change mitigation and adaptation strategies. The strong performance by certain mixtures of life-forms, especially tall forbs, grasses and succulents, warrants further investigation into niche complementarity or facilitation as mechanisms governing biodiversity-ecosystem functioning relationships in green roof ecosystems. PMID- 20300195 TI - A role for methyl-CpG binding domain protein 2 in the modulation of the estrogen response of pS2/TFF1 gene. AB - BACKGROUND: In human Estrogen Receptor alpha (ERalpha)-positive breast cancers, 5' end dense methylation of the estrogen-regulated pS2/TFF1 gene correlates with its transcriptional inhibition. However, in some ERalpha-rich biopsies, pS2 expression is observed despite the methylation of its TATA-box region. Herein, we investigated the methylation-dependent mechanism of pS2 regulation. METHODOLOGY/PRINCIPAL FINDINGS: We observed interplay between Methyl-CpG Binding Domain protein 2 (MBD2) transcriptional repressor and ERalpha transactivator: (i) the pS2 gene is poised for transcription upon demethylation limited to the enhancer region containing the estrogen responsive element (ERE); (ii) MBD2 binding sites overlapped with the methylation status of the pS2 5' end; (iii) MBD2 depletion elevated pS2 expression and ectopic expression of ERalpha partially overcame the inhibitory effect of MBD2 when the ERE is unmethylated. Furthermore, serial chromatin immunoprecipitation assays indicated that MBD2 and ERalpha could simultaneously occupy the same pS2 DNA molecule; (iv) concomitant ectopic ERalpha expression and MBD2 depletion resulted in synergistic transcriptional stimulation, while the pS2 promoter remains methylated. CONCLUSIONS/SIGNIFICANCE: MBD2 and ERalpha drive opposite effects on pS2 expression, which are associated with specific steady state levels of histone H3 acetylation and methylation marks. Thus, epigenetic silencing of pS2 could be dependent on balance of the relative intracellular concentrations of ERalpha and MBD2. PMID- 20300197 TI - Hypoxia promotes glycogen accumulation through hypoxia inducible factor (HIF) mediated induction of glycogen synthase 1. AB - When oxygen becomes limiting, cells reduce mitochondrial respiration and increase ATP production through anaerobic fermentation of glucose. The Hypoxia Inducible Factors (HIFs) play a key role in this metabolic shift by regulating the transcription of key enzymes of glucose metabolism. Here we show that oxygen regulates the expression of the muscle glycogen synthase (GYS1). Hypoxic GYS1 induction requires HIF activity and a Hypoxia Response Element within its promoter. GYS1 gene induction correlated with a significant increase in glycogen synthase activity and glycogen accumulation in cells exposed to hypoxia. Significantly, knockdown of either HIF1alpha or GYS1 attenuated hypoxia-induced glycogen accumulation, while GYS1 overexpression was sufficient to mimic this effect. Altogether, these results indicate that GYS1 regulation by HIF plays a central role in the hypoxic accumulation of glycogen. Importantly, we found that hypoxia also upregulates the expression of UTP:glucose-1-phosphate urydylyltransferase (UGP2) and 1,4-alpha glucan branching enzyme (GBE1), two enzymes involved in the biosynthesis of glycogen. Therefore, hypoxia regulates almost all the enzymes involved in glycogen metabolism in a coordinated fashion, leading to its accumulation. Finally, we demonstrated that abrogation of glycogen synthesis, by knock-down of GYS1 expression, impairs hypoxic preconditioning, suggesting a physiological role for the glycogen accumulated during chronic hypoxia. In summary, our results uncover a novel effect of hypoxia on glucose metabolism, further supporting the central importance of metabolic reprogramming in the cellular adaptation to hypoxia. PMID- 20300198 TI - Anti-inflammatory effects of licorice and roasted licorice extracts on TPA induced acute inflammation and collagen-induced arthritis in mice. AB - The anti-inflammatory activity of licorice (LE) and roasted licorice (rLE) extracts determined in the murine phorbol ester-induced acute inflammation model and collagen-induced arthritis (CIA) model of human rheumatoid arthritis. rLE possessed greater activity than LE in inhibiting phorbol ester-induced ear edema. Oral administration of LE or rLE reduced clinical arthritis score, paw swelling, and histopathological changes in a murine CIA. LE and rLE decreased the levels of proinflammatory cytokines in serum and matrix metalloproteinase-3 expression in the joints. Cell proliferation and cytokine secretion in response to type II collagen or lipopolysaccharide stimulation were suppressed in spleen cells from LE or rLE-treated CIA mice. Furthermore, LE and rLE treatment prevented oxidative damages in liver and kidney tissues of CIA mice. Taken together, LE and rLE have benefits in protecting against both acute inflammation and chronic inflammatory conditions including rheumatoid arthritis. rLE may inhibit the acute inflammation more potently than LE. PMID- 20300199 TI - GABA(C) Receptors in the Lateral Amygdala: A Possible Novel Target for the Treatment of Fear and Anxiety Disorders? AB - Activation of GABA(A)Rs in the lateral nucleus of the amygdala (LA), a key site of plasticity underlying fear learning, impairs fear learning. The role of GABA(C)Rs in the LA and other brain areas is poorly understood. GABA(C)Rs could be an important novel target for pharmacological treatments of anxiety-related disorders since, unlike GABA(A)Rs, GABA(C)Rs do not desensitize. To detect functional GABA(C)Rs in the LA we performed whole cell patch clamp recordings in vitro. We found that GABA(A)Rs and GABA(B)Rs blockade lead to a reduction of evoked inhibition and an increase increment of excitation, but activation of GABA(C)Rs caused elevations of evoked excitation, while blocking GABA(C)Rs reduced evoked excitation. Based on this evidence we tested whether GABA(C)Rs in LA contribute to fear learning in vivo. It is established that activation of GABA(A)Rs leads to blockage of fear learning. Application of GABA(C) drugs had a very different effect; fear learning was enhanced by activating and attenuated by blocking GABA(C)Rs in the LA. Our results suggest that GABA(C) and GABA(A)Rs play opposing roles in modulation of associative plasticity in LA neurons of rats. This novel role of GABA(C)Rs furthers our understanding of GABA receptors in fear memory acquisition and storage and suggests a possible novel target for the treatment of fear and anxiety disorders. PMID- 20300200 TI - A cognitive training intervention increases resting cerebral blood flow in healthy older adults. AB - Healthy aging is typically accompanied by some decline in cognitive performance, as well as by alterations in brain structure and function. Here we report the results of a randomized, controlled trial designed to determine the effects of a novel cognitive training program on resting cerebral blood flow (CBF) and gray matter (GM) volume in healthy older adults. Sixty-six healthy older adults participated in 8 weeks of either a training program targeting attention and distractibility or an educational control program. This training program produced significantly larger increases in resting CBF to the prefrontal cortex than the control program. Increases in blood flow were associated with reduced susceptibility to distraction after training, but not with alterations in GM volume. These data demonstrate that cognitive training can improve resting CBF in healthy older adults and that cerebral perfusion rates may be a more sensitive indicator of the benefits of cognitive training than volumetric analyses. PMID- 20300201 TI - Mutations in ARX Result in Several Defects Involving GABAergic Neurons. AB - Genetic investigations of X-linked mental retardation have demonstrated the implication of ARX in a wide spectrum of disorders extending from phenotypes with severe neuronal migration defects, such as lissencephaly, to mild or moderate forms of mental retardation without apparent brain abnormalities, but with associated features of dystonia and epilepsy. These investigations have in recent years directed attention to the role of this gene in brain development. Analysis of its spatio-temporal localization profile revealed expression in telencephalic structures at all stages of development, mainly restricted to populations of GABA containing neurons. Furthermore, studies of the effects of ARX loss of function either in humans or in lines of mutant mice revealed varying defects, suggesting multiple roles of this gene during development. In particular, Arx has been shown to contribute to almost all fundamental processes of brain development: patterning, neuronal proliferation and migration, cell maturation and differentiation, as well as axonal outgrowth and connectivity. In this review, we will present and discuss recent findings concerning the role of ARX in brain development and how this information will be useful to better understand the pathophysiological mechanisms of mental retardation and epilepsy associated with ARX mutations. PMID- 20300202 TI - A rapid and reliable method of counting neurons and other cells in brain tissue: a comparison of flow cytometry and manual counting methods. AB - It is of critical importance to understand the numbers and distributions of neurons and non-neurons in the cerebral cortex because cell numbers are reduced with normal aging and by diseases of the CNS. The isotropic fractionator method provides a faster way of estimating numbers of total cells and neurons in whole brains and dissected brain parts. Several comparative studies have illustrated the accuracy and utility of the isotropic fractionator method, yet it is a relatively new methodology, and there is opportunity to adjust procedures to optimize its efficiency and minimize error. In the present study, we use 142 samples from a dissected baboon cortical hemisphere to evaluate if isotropic fractionator counts using a Neubauer counting chamber and fluorescence microscopy could be accurately reproduced using flow cytometry methods. We find greater repeatability in flow cytometry counts, and no evidence of constant or proportional bias when comparing microscopy to flow cytometry counts. We conclude that cell number estimation using a flow cytometer is more efficient and more precise than comparable counts using a Neubauer chamber on a fluorescence microscope. This method for higher throughput, precise estimation of cell numbers has the potential to rapidly advance research in post-mortem human brains and vastly improve our understanding of cortical and subcortical structures in normal, injured, aged, and diseased brains. PMID- 20300203 TI - The IKK complex, a central regulator of NF-kappaB activation. AB - The IKK kinase complex is the core element of the NF-kappaB cascade. It is essentially made of two kinases (IKKalpha and IKKbeta) and a regulatory subunit, NEMO/IKKgamma. Additional components may exist, transiently or permanently, but their characterization is still unsure. In addition, it has been shown that two separate NF-kappaB pathways exist, depending on the activating signal and the cell type, the canonical (depending on IKKbeta and NEMO) and the noncanonical pathway (depending solely on IKKalpha). The main question, which is still only partially answered, is to understand how an NF-kappaB activating signal leads to the activation of the kinase subunits, allowing them to phosphorylate their targets and eventually induce nuclear translocation of the NF-kappaB dimers. I will review here the genetic, biochemical, and structural data accumulated during the last 10 yr regarding the function of the three IKK subunits. PMID- 20300204 TI - Single-molecule and superresolution imaging in live bacteria cells. AB - Single-molecule imaging enables biophysical measurements devoid of ensemble averaging, gives enhanced spatial resolution beyond the diffraction limit, and permits superresolution reconstructions. Here, single-molecule and superresolution imaging are applied to the study of proteins in live Caulobacter crescentus cells to illustrate the power of these methods in bacterial imaging. Based on these techniques, the diffusion coefficient and dynamics of the histidine protein kinase PleC, the localization behavior of the polar protein PopZ, and the treadmilling behavior and protein superstructure of the structural protein MreB are investigated with sub-40-nm spatial resolution, all in live cells. PMID- 20300205 TI - The nuclear envelope. AB - The nuclear envelope (NE) is a highly regulated membrane barrier that separates the nucleus from the cytoplasm in eukaryotic cells. It contains a large number of different proteins that have been implicated in chromatin organization and gene regulation. Although the nuclear membrane enables complex levels of gene expression, it also poses a challenge when it comes to cell division. To allow access of the mitotic spindle to chromatin, the nucleus of metazoans must completely disassemble during mitosis, generating the need to re-establish the nuclear compartment at the end of each cell division. Here, I summarize our current understanding of the dynamic remodeling of the NE during the cell cycle. PMID- 20300206 TI - The isoforms of the p53 protein. AB - p53 is a transcription factor with a key role in the maintenance of genetic stability and therefore preventing cancer formation. It belongs to a family of genes composed of p53, p63, and p73. The p63 and p73 genes have a dual gene structure with an internal promoter in intron-3 and together with alternative splicing, can express 6 and 29 mRNA variants, respectively. Such a complex expression pattern had not been previously described for the p53 gene, which was not consistent with our understanding of the evolution of the p53 gene family. Consequently, we revisited the human p53 gene structure and established that it encodes nine different p53 protein isoforms because of alternative splicing, alternative promoter usage, and alternative initiation sites of translation. Therefore, the human p53 gene family (p53, p63, and p73) has a dual gene structure. We determined that the dual gene structure is conserved in Drosophila and in zebrafish p53 genes. The conservation through evolution of the dual gene structure suggests that the p53 isoforms play an important role in p53 tumor suppressor activity. We and others have established that the p53 isoforms can regulate cell-fate outcome in response to stress, by modulating p53 transcriptional activity in a promoter and stress-dependent manner. We have also shown that the p53 isoforms are abnormally expressed in several types of human cancers, suggesting that they play an important role in cancer formation. The determination of p53 isoforms' expression may help to link clinical outcome to p53 status and to improve cancer patient treatment. PMID- 20300207 TI - Clinical outcomes and correlates of TP53 mutations and cancer. AB - The initial observation that p53 accumulation might serve as a surrogate biomarker for TP53 mutation has been the cornerstone for vast translational efforts aimed at validating its clinical use for the diagnosis, prognosis, and treatment of cancer. Early on, it was realized that accurate evaluation of p53 status and function could not be achieved through protein-expression analysis only. As our understanding of the p53 pathway has evolved and more sophisticated methods for assessment of p53 functional integrity have become available, the clinical and molecular epidemiological implications of p53 abnormalities in cancers are being revealed. They include diagnostic testing for germline p53 mutations, and the assessment of selected p53 mutations as biomarkers of carcinogen exposure and cancer risk and prognosis. Here, we describe the strengths and limitations of the most frequently used techniques for determination of p53 status in tumors, as well as the most remarkable latest findings relating to its clinical and epidemiological value. PMID- 20300208 TI - Auxin and monocot development. AB - Monocots are known to respond differently to auxinic herbicides; hence, certain herbicides kill broadleaf (i.e., dicot) weeds while leaving lawns (i.e., monocot grasses) intact. In addition, the characters that distinguish monocots from dicots involve structures whose development is controlled by auxin. However, the molecular mechanisms controlling auxin biosynthesis, homeostasis, transport, and signal transduction appear, so far, to be conserved between monocots and dicots, although there are differences in gene copy number and expression leading to diversification in function. This article provides an update on the conservation and diversification of the roles of genes controlling auxin biosynthesis, transport, and signal transduction in root, shoot, and reproductive development in rice and maize. PMID- 20300209 TI - Auxin transporters--why so many? AB - Interacting and coordinated auxin transporter actions in plants underlie a flexible network that mobilizes auxin in response to many developmental and environmental changes encountered by these sessile organisms. The independent but synergistic activity of individual transporters can be differentially regulated at various levels. This invests auxin transport mechanisms with robust functional redundancy and added auxin flow capacity when needed. An evolutionary perspective clarifies the roles of the different transporter groups in plant development. Mathematical and functional analysis of elements of auxin transport makes it possible to rationalize the relative contributions of members of the respective transporter classes to the localized auxin transport streams that then underlie both preprogrammed developmental changes and reactions to environmental stimuli. PMID- 20300210 TI - Motor axon pathfinding. AB - Motor neurons are functionally related, but represent a diverse collection of cells that show strict preferences for specific axon pathways during embryonic development. In this article, we describe the ligands and receptors that guide motor axons as they extend toward their peripheral muscle targets. Motor neurons share similar guidance molecules with many other neuronal types, thus one challenge in the field of axon guidance has been to understand how the vast complexity of brain connections can be established with a relatively small number of factors. In the context of motor guidance, we highlight some of the temporal and spatial mechanisms used to optimize the fidelity of pathfinding and increase the functional diversity of the signaling proteins. PMID- 20300211 TI - Molecular and cellular mechanisms of lamina-specific axon targeting. AB - The specificity of synaptic connections is directly related to the functional integrity of neural circuits. Long-range axon guidance and topographic mapping mechanisms bring axons into spatial proximity of target cells and thus limit the number of potential synaptic partners. Synaptic specificity is then achieved by extracellular short-range guidance cues and cell-surface recognition cues. Neural activity may enhance the precision and strength of specific circuit connections. Here, we focus on one of the final steps of synaptic matchmaking: the targeting of synaptic layers and the mutual recognition of axons and dendrites within these layers. PMID- 20300213 TI - The organic composition of carbonaceous meteorites: the evolutionary story ahead of biochemistry. AB - Carbon-containing meteorites provide a natural sample of the extraterrestrial organic chemistry that occurred in the solar system ahead of life's origin on the Earth. Analyses of 40 years have shown the organic content of these meteorites to be materials as diverse as kerogen-like macromolecules and simpler soluble compounds such as amino acids and polyols. Many meteoritic molecules have identical counterpart in the biosphere and, in a primitive group of meteorites, represent the majority of their carbon. Most of the compounds in meteorites have isotopic compositions that date their formation to presolar environments and reveal a long and active cosmochemical evolution of the biogenic elements. Whether this evolution resumed on the Earth to foster biogenesis after exogenous delivery of meteoritic and cometary materials is not known, yet, the selective abundance of biomolecule precursors evident in some cosmic environments and the unique L-asymmetry of some meteoritic amino acids are suggestive of their possible contribution to terrestrial molecular evolution. PMID- 20300212 TI - Human genetic disorders of axon guidance. AB - This article reviews symptoms and signs of aberrant axon connectivity in humans, and summarizes major human genetic disorders that result, or have been proposed to result, from defective axon guidance. These include corpus callosum agenesis, L1 syndrome, Joubert syndrome and related disorders, horizontal gaze palsy with progressive scoliosis, Kallmann syndrome, albinism, congenital fibrosis of the extraocular muscles type 1, Duane retraction syndrome, and pontine tegmental cap dysplasia. Genes mutated in these disorders can encode axon growth cone ligands and receptors, downstream signaling molecules, and axon transport motors, as well as proteins without currently recognized roles in axon guidance. Advances in neuroimaging and genetic techniques have the potential to rapidly expand this field, and it is feasible that axon guidance disorders will soon be recognized as a new and significant category of human neurodevelopmental disorders. PMID- 20300214 TI - SLAM-family receptors: immune regulators with or without SAP-family adaptors. AB - The signaling lymphocytic activation molecule (SLAM) family of receptors and the SLAM-associated protein (SAP) family of intracellular adaptors are expressed in immune cells. By way of their cytoplasmic domain, SLAM-related receptors physically associate with SAP-related adaptors. Evidence is accumulating that the SLAM and SAP families play crucial roles in multiple immune cell types. Moreover, the prototype of the SAP family, that is SAP, is mutated in a human immunodeficiency, X-linked lymphoproliferative (XLP) disease. In the presence of SAP-family adaptors, the SLAM family usually mediates stimulatory signals that promote immune cell activation or differentiation. In the absence of SAP-family adaptors, though, the SLAM family undergoes a "switch-of-function," thereby mediating inhibitory signals that suppress immune cell functions. The molecular basis and significance of this mechanism are discussed herein. PMID- 20300216 TI - Symmetry breaking in biology. AB - Symmetry breaking is essential for cell movement, polarity, and developmental patterning. Amplification of initial asymmetry is key to the conserved mechanisms involved. PMID- 20300215 TI - Signaling to NF-kappaB: regulation by ubiquitination. AB - The NF-kappaB pathway is a ubiquitous stress response that activates the NF kappaB family of transcription factors. Antigen receptors, receptors of the innate immune system, and certain intracellular stressors are potent activators of this pathway. The transcriptional program that is activated is both antiapoptotic and highly proinflammatory. Indeed, any compromise in engagement of the pathway results in immunodeficiency, whereas constitutive activation generates a sustained inflammatory response that may promote malignancy. As such, NF-kappaB activation is under tight regulation by a number of post-translational modifications, including phosphorylation and ubiquitination. This article attempts to synthesize our current knowledge regarding the regulation of NF kappaB signaling by ubiquitination, specifically highlighting the biochemical basis for both positive and negative feedback loops that function in unison to generate coordinated signals that are essential for the viability of metazoan animals. PMID- 20300218 TI - The air liquid-interface, a skin microenvironment, promotes growth of melanoma cells, but not their apoptosis and invasion, through activation of mitogen activated protein kinase. AB - The air-liquid interface (ALI) is a common microenvironment of the skin, but it is unknown whether the ALI affects melanoma cell behaviors. Using a collagen gel invasion assay, immunohistochemistry, and Western blots, here we show that melanoma cell proliferation in cultures with an ALI is higher than melanoma cell proliferation in submerged cultures. Bromodeoxyuridine (BrdU) uptake, an indicator of cell proliferation, of melanoma cells at the ALI was about 3 times that of submerged cells, while ALI and submerged melanoma cells had similar levels of single-stranded DNA (a marker of apoptosis). The ALI enhanced the expression of Raf-1, MEK-1 and pERK-1/2 components of the mitogen-activated protein kinase (MAPK) cascade, in cells more than the submerged condition did. The increases in BrdU uptake and pERK-1/2 expression promoted by ALI was abolished by the MEK inhibitor, PD-98059. ALI-treated and submerged melanoma cells did not infiltrate into the collagen gel, and they showed no significant difference in the expression of the invasion- and motility-related molecules, matrix metalloproteinase-1 and -9, laminin 5, and filamin A. Our data indicate that the ALI, a skin microenvironment, accelerates the growth, but not the apoptosis or invasion, of melanoma cells through MAPK activation. PMID- 20300219 TI - Potential involvement of the stem cell factor receptor c-kit in alopecia areata and androgenetic alopecia: histopathological, immunohistochemical, and semiquantitative investigations. AB - Alopecia areata (AAR) and androgenetic alopecia (AGA) are two major forms of alopecia based on altered hair growth condition. In general, the cell cycle is regulated by several mechanisms including the stem cell factor/c-kit signaling. To assess a role for stem cell activity in alopecia, we performed histopathological, immunohistochemical, and semiquantitative analyses of c-kit as well as Ki-67 in scalp biopsy specimens obtained from 14 patients with AAR, 18 patients with AGA, and 6 age-matched control subjects, using the specific antibodies. Formalin-fixed, paraffin-embedded skin sections were examined. Immunoreactivities for Ki-67 and c-kit were localized in keratinocytes and melanocytes in the outermost layer of hair follicles. The mean length of hair follicles was significantly shorter in the AAR and AGA groups than in the control group. The mean number of Ki-67-immunoreactive cells per follicle was significantly reduced in the AAR and AGA groups as compared with the control group. The mean number of c-kit-immunoreactive cells per follicle was significantly increased in the AAR and AGA groups as compared with the control group. Our results indicate that c-kit is upregulated in the hair follicle cells in these forms of alopecia, and suggest that the upregulation reflects a negative feedback mechanism in response to possible downregulation of the ligand stem cell factor. PMID- 20300217 TI - Chromosome territories. AB - Chromosome territories (CTs) constitute a major feature of nuclear architecture. In a brief statement, the possible contribution of nuclear architecture studies to the field of epigenomics is considered, followed by a historical account of the CT concept and the final compelling experimental evidence of a territorial organization of chromosomes in all eukaryotes studied to date. Present knowledge of nonrandom CT arrangements, of the internal CT architecture, and of structural interactions with other CTs is provided as well as the dynamics of CT arrangements during cell cycle and postmitotic terminal differentiation. The article concludes with a discussion of open questions and new experimental strategies to answer them. PMID- 20300220 TI - Sexual impairment and its effects on quality of life in patients with rectal cancer. AB - BACKGROUND: The effects of rectal surgery on patients' postoperative quality of life (QOL) and sexual function has been little studied to date. The present study aims to address this issue. METHODS: 519 patients who had undergone surgery for rectal cancer from January 1997 to January 2003 were included in the study. The EORTC-QLQ-C-30 questionnaire and an additional, tumor-specific module were administered prospectively multiple times over a 2-year period: before surgery, on discharge from the hospital, and at 3, 6, 12, and 24 months after surgery. Comparisons were made between men and women, different age groups, and different surgical procedures: abdominoperineal resection (APR) versus anterior resection (AR). RESULTS: There were significant differences between men and women on scales of function and symptoms. Women had worse scores for physical function and overall quality of life and higher values for fatigue. Sexual life was impaired in both men and women, but the impairment was significantly more severe in men, and men felt more distressed by it than women did. Physical function and overall quality of life were better in patients aged 69 and younger, while patients aged 70 and older suffered from fatigue. Younger patients had a more severe impairment of sexuality, which, over the time period of the study, led to severe emotional symptoms. Sexuality was more severely impaired in patients who had undergone APR than in those who had undergone AR. CONCLUSION: These findings show that the quality of life is changed by surgery for rectal cancer and is influenced by the patient's sex and age, as well as by the particular surgical approach used. PMID- 20300221 TI - Home telemonitoring in patients with chronic heart failure: a chance to improve patient care? AB - BACKGROUND: Telemonitoring can improve the medical care, quality of life, and prognosis of chronically ill patients. This review article summarizes the current status of health services research on telemonitoring, focusing on patients with chronic congestive heart failure. METHOD: The Medline database was selectively searched for articles appearing from June 2001 to May 2008, with an emphasis on randomized, controlled trials. RESULTS: The available scientific data on vital signs monitoring are limited, yet there is evidence for a positive effect on some clinical endpoints, particularly mortality. Nonetheless, any possible improvement of patient-reported outcomes, such as the quality of life, still remains to be demonstrated. CONCLUSIONS: The data suggest that telemonitoring is effective, yet there is no evidence for superior outcomes with any particular model of care incorporating telemonitoring (i.e., monitoring of vital signs versus structured telephone monitoring). A valid criticism is that the individual components of home telemonitoring have not yet been separately tested in order to compare their individual effects. PMID- 20300223 TI - Correspondence (letter to the editor): Hand hygiene prevents MRSA transmission. PMID- 20300225 TI - Correspondence (letter to the editor): Controlled cyclophotocoagulation. PMID- 20300226 TI - Current trends in mathematical modeling of high-temperature thermal therapies. PMID- 20300227 TI - Considerations for thermal injury analysis for RF ablation devices. AB - BACKGROUND: The estimation of lesion size is an integral part of treatment planning for the clinical applications of radiofrequency ablation. However, to date, studies have not directly evaluated the impact of different computational estimation techniques for predicting lesion size. In this study, we focus on three common methods used for predicting tissue injury: (1) iso-temperature contours, (2) Cumulative equivalent minutes, (3) Arrhenius based thermal injury. METHODS: We created a geometric model of a multi-tyne ablation electrode and simulated thermal and tissue injury profiles that result from three calculation methods after 15 minutes exposure to a constant RF voltage source. A hybrid finite element technique was used to calculate temperature and tissue injury. Time-temperature curves were used in the assessment of iso-temperature thresholds and the method of cumulative equivalent minutes. An Arrhenius-based formulation was used to calculate sequential and recursive thermal injury to tissues. RESULTS: The data demonstrate that while iso-temperature and cumulative equivalent minute contours are similar in shape, these two methodologies grossly over-estimate the amount of tissue injury when compared to recursive thermal injury calculations, which have previously been shown to correlate closely with in vitro pathologic lesion volume measurement. In addition, Arrhenius calculations that do not use a recursive algorithm result in a significant underestimation of lesion volume. The data also demonstrate that lesion width and depth are inadequate means of characterizing treatment volume for multi-tine ablation devices. CONCLUSIONS: Recursive thermal injury remains the most physiologically relevant means of computationally estimating lesion size for hepatic tumor applications. Iso-thermal and cumulative equivalent minute approaches may produce significant errors in the estimation of lesion size. PMID- 20300228 TI - Preliminary Study of Coagulation Monitoring by Antenna for Treatment during Microwave Coagulation Therapy. AB - Microwave coagulation therapy (MCT) has been employed mainly for treatment of small size tumors. In the treatment, thin microwave antenna is inserted into the tumor and microwave energy heats up the tumor up to at least 60 degrees C for generation of enough coagulated volume including the target tumor. During the microwave radiation, reflection coefficient of treatment antenna changes significantly. In this paper, possibility of coagulation monitoring was found observing the reflection coefficient change of the antenna by numerical calculations and measurements. PMID- 20300230 TI - Editors' note. PMID- 20300229 TI - Mathematical modeling of epicardial RF ablation of atrial tissue with overlying epicardial fat. AB - The efficacy of treating atrial fibrillation by RF ablation on the epicardial surface is currently under question due to the presence of epicardial adipose tissue interposed between the ablation electrode and target site (atrial wall). The problem is probably caused by the electrical conductivity of the fat (0.02 S/m) being lower than that of the atrial tissue (0.4-0.6 S/m). Since our objective is to improve epicardial RF ablation techniques, we planned a study based on a two-dimensional mathematical model including an active electrode, a fragment of epicardial fat over a fragment of atrial tissue, and a section of atrium with circulating blood. Different procedures for applying RF power were studied, such as varying the frequency, using a cooled instead of a dry electrode, and different modes of controlling RF power (constant current, temperature and voltage) for different values of epicardial fat thickness. In general, the results showed that the epicardial fat layer seriously impedes the passage of RF current, thus reducing the effectiveness of atrial wall RF ablation. PMID- 20300231 TI - Balloon pulmonary valvotomy as interim palliation for symptomatic young infants with tetralogy of Fallot. AB - OBJECTIVES: To describe the case selection, technique and immediate and short term results of balloon pulmonary valvotomy (BPV) in young infants with tetralogy of Fallot (TOF). BACKGROUND: Symptomatic young infants with TOF can either undergo corrective surgery or Blalock-Taussig (BT) shunt. Corrective surgery in early infancy is associated with significant morbidity and is not a realistic option in many centers. BT shunt carries the risk of branch pulmonary artery distortion and shunt occlusion. METHODS: Infants less than three months with a significant valvar pulmonary stenosis (with or without associated infundibular and annular component) and oxygen saturation G base pair change leads to decrease in the stability of the protein. A reproducible and a cost-effective PCR-RFLP based assay was developed to screen for the SNP among population data. This SNP has been studied in Caucasian, Asian, and African American populations. Till date, no data is available on Indian population. The distribution of M510I NPC1L1 genotype was estimated in the North Western Indian Population as a test case. The allele distribution in Indian Population differs significantly from that of other populations. The methodology thus proved to be robust enough to bring out these differences. PMID- 20300302 TI - Apolipoprotein E gene polymorphism and dyslipidaemia in adult Asian Indians: A population based study from Calcutta, India. AB - AIM: The study was aimed to determine the association of Apolipoprotein E (apo E) gene polymorphisms on lipid levels in Asian Indian population. METHODS: A total of 350 (184 males and 166 females) adult (30 years and above) Asian Indians of Calcutta and suburb participated in the study. Anthropometric measures, lipids profiles, and blood glucose measures were collected. Out of 350 subjects, a sample of 70 individuals was selected randomly for genotyping after adjusting for age and sex. The apo E gene polymorphisms were determined by agarose gel electrophoresis. RESULTS: The apo E polymorphism showed significant association with dyslipidaemia (P=0.0135) with epsilon3/4 combination has had the highest occurrence of dyslipidaemia and metabolic syndrome (MS) followed by epsilon4/4 24 years old, with the same ratio of males to females in both groups. The diagnosis of T1D was made on the basis of ketoacidosis or ketosis with severe symptoms of acute onset at presentation and continuous dependence on insulin. Controls were negative for anti-GAD antibodies and were greater than 24 years of age. Genotyping was performed using single strand conformation polymorphism (SSCP), temperature gradient gel electrophoresis (TGGE), and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). RESULTS: The results demonstrated an association of the C-819T and A+49G SNPs in the CTLA-4 gene with T1D patients (P=0.0047) and (P=0.000575), respectively. Moreover, this association was stratified by gender and age to female patients with age at onset 0-5 years old (P=0.0186) and (P=0.00115) more than male patient with the age at onset 0-5 years old (P= 0.3120) and (P=0.345161), respectively. CONCLUSION: The results support an association of the C-819T and A+49G SNPs in the CTLA-4 gene with Egyptian children, specifically, females of onset age 0-5 years old. PMID- 20300305 TI - Bloom's syndrome in a 12-year-old Iranian girl. AB - BACKGROUND: Bloom's syndrome, an autosomal recessive inherited disorder, belongs to the group of chromosomal breakage syndromes. The clinical diagnosis of BS is confirmed cytogenetically. Its frequency in the general population is unknown but it is common in eastern European Ashkenazi Jews. CASE REPORT: A 12-year-old girl was referred to us because of short stature. She was the second child of the first cousin marriage. She had a slender body frame, short stature, and microcephaly. Her face was long and narrow with prominent nose, and malar and mandibular hypoplasia. The spots of hyper and hypo pigmentation were observed in the trunk and limbs. Telangectasia spots were observed in some areas of the trunk. Additionally, generalized hirsutism was present in the whole body. Cytogenetic findings revealed an abnormality in the structural chromosome. CONCLUSION: This is the first BS case that has been reported in Iranian female population. PMID- 20300306 TI - The Moroccan human mutation database. PMID- 20300307 TI - An optimised method for quantifying glenoid orientation. AB - A robust quantification method is essential for inter-subject glenoid comparison and planning of total shoulder arthroplasty. This study compared various scapular and glenoid axes with each other in order to optimally define the most appropriate method of quantifying glenoid version and inclination.Six glenoid and eight scapular axes were defined and quantified from identifiable landmarks of twenty-one scapular image scans. Pathology independency and insensitivity of each axis to inter-subject morphological variation within its region was tested. Glenoid version and inclination were calculated using the best axes from the two regions.The best glenoid axis was the normal to a least-square plane fit on the glenoid rim, directed approximately medio-laterally. The best scapular axis was the normal to a plane formed by the spine root and lateral border ridge. Glenoid inclination was 15.7 degrees +/- 5.1 degrees superiorly and version was 4.9 degrees +/- 6.1 degrees , retroversion.The choice of axes in the present technique makes it insensitive to pathology and scapular morphological variabilities. Its application would effectively improve inter-subject glenoid version comparison, surgical planning and design of prostheses for shoulder arthroplasty. PMID- 20300308 TI - An electromyographic analysis of shoulder muscle activation during push-up variations on stable and labile surfaces. AB - BACKGROUND: Numerous exercises are used to strengthen muscles around the shoulder joint including the push-up and the push-up plus. An important consideration is the addition of surface instability in the form of swiss ball for rehabilitation and strength. The justification for the use of the swiss ball is based on its potential for increasing muscular demand required to maintain postural stability and for improving joint proprioception. Evidence for this is lacking in literature. PURPOSE OF THE STUDY: To compare the myoelectric amplitude of shoulder muscles during push-ups on labile and stable surface. STUDY DESIGN: Same subject experimental study. MATERIALS AND METHODS: Thirty healthy male subjects in the age group 20-30 years with a mean height of 173.65 cm (+/- SD 2.56) and a mean weight of 69.9 kg (+/-SD 0.2) were taken. Surface electromyogram was recorded from triceps, pectoralis major, serratus anterior and upper trapezius while performing push-up and push-up plus exercises, both on labile and stable surface. RESULTS: Significant increase in muscle activity was observed in pectoralis major and triceps muscle (only during eccentric phase of elbow pushups), while serratus anterior and upper trapezius showed no change in activation level on swiss ball. CONCLUSION: The addition of a swiss ball is capable of influencing shoulder muscle activity during push-up variations, although the effect is task and muscle dependent. PMID- 20300309 TI - Early arthroscopic release in stiff shoulder. AB - PURPOSE: To evaluate the results of early arthroscopic release in the patients of stiff shoulder METHODS: Twenty patients of stiff shoulder, who had symptoms for at least three months and failed to improve with steroid injections and physical therapy of 6 weeks duration, underwent arthroscopic release. The average time between onset of symptoms and the time of surgery was 4 months and 2 weeks. The functional outcome was evaluated using ASES and Constant and Murley scoring systems. RESULTS: All the patients showed significant improvement in the range of motion and relief of pain by end of three months following the procedure. At 12 months, mean improvement in ASES score is 38 points and Constant and Murley score is 4O.5 points. All patients returned to work by 3-5 months (average -4.5 months). CONCLUSION: Early arthroscopic release showed promising results with reliable increase in range of motion, early relief of symptoms and consequent early return to work. So it is highly recommended in properly selected patients. LEVEL OF EVIDENCE: Level IV. PMID- 20300310 TI - Perioperative fracture-dislocation of the humeral head during a resurfacing hemiarthroplasty. AB - We report a case of perioperative fracture-dislocation of the humeral head produced during the reaming for a resurfacing replacement hemiarthroplasty (RRH) in a 79-year old woman. This is a surgical complication not previously described in the literature for this type of prosthesis design. Resurfacing humeral head implant has been noted as a useful treatment for glenohumeral arthropathies, also in elderly people, with a very low incidence of complications. However, as we report, they are possible.It is advisable that conventional stemmed implants could be available when RRH is performed. PMID- 20300311 TI - Modified arthroscopic double row repair of partial thickness tear of the rotator Cuff involving articular and bursal side. AB - Partial thickness of rotator cuff tears is considered as a common cause of shoulder disability. Various techniques for arthroscopic repair of partial thickness tear of rotator cuff have been reported in the literature. These techniques have addressed the articular side partial thickness cuff tear. We present an arthroscopic repair of partial thickness tear of rotator cuff involving both articular and bursal surfaces without converting into a full thickness tear. Each side of the tear was repaired with suture anchors separately. PMID- 20300312 TI - Diclofenac patches for postoperative shoulder pain. PMID- 20300313 TI - Pulmonary embolism following rotator cuff repair. AB - BACKGROUND: Previous studies have provided data on the incidence of pulmonary embolism following shoulder arthroplasty and repair of fractures of the proximal humerus. However, there is no information on the risk of pulmonary embolism following the surgical management of rotator cuff tears. METHODS: We performed a review of 1176 patients who underwent operative procedures for rotator cuff tears between January 1(st), 2001 and December 31(st), 2005 to identify all patients who developed a symptomatic pulmonary embolism postoperatively. RESULTS: Three patients developed pulmonary embolisms that were diagnosed with computed tomography angiography. The overall incidence was calculated to be 0.26%. None of the patients died as a result of the pulmonary embolism. CONCLUSIONS: The data from this review indicates that the risk of pulmonary embolism following surgery for rotator cuff repair is low, but not nonexistent. The most common presenting symptoms of pulmonary embolism were chest pain, shortness of breath, and hypoxia. This study should raise surgeons' awareness about this possible complication following rotator cuff repair surgery. PMID- 20300314 TI - A contribution to the calculation of a safe deltoid split. AB - PURPOSE: Traditional teaching suggests that a safe deltoid split should extend no more than 5 cm from the lateral edge of the acromion. However, there are reports of nerves lying within this distance. Our aim was to redefine the safe maximum split and also to study the influence of arm length and position. MATERIALS AND METHODS: Thirty cadaveric shoulders were dissected using the deltoid-splitting approach and the acromion-axillary nerve distance was measured in the neutral position, in abduction, and in adduction. This was correlated to upper arm length. Deltoid splits were measured at the end of 13 deltoid-splitting shoulder operations. RESULTS: The mean acromion-axillary nerve distance was 6.0 cm (SD 0.6; range 4.5-6.5). Abduction brought the nerve closer by 1.5 cm. There was a strong correlation with upper arm length (r = 0.82) but the presence of high individual variability did not allow calculation of a safe deltoid split. The mean deltoid split in 13 open shoulder operations was 3.4 cm. CONCLUSIONS: Taking the mean acromion-axillary nerve distance minus three standard deviations as the safe deltoid split would protect 99.7% of nerves. Therefore we recommend that the maximum deltoid split should be 4.2 cm; this distance would be sufficient to preserve all nerves in our study as well as all those reported by other authors. Splitting the deltoid in abduction should be avoided. CLINICAL RELEVANCE: The traditional 5-cm deltoid split is probably too generous. We believe 4.2 cm is a safer limit. PMID- 20300316 TI - Giant cell tumor along with secondary aneurysmal bone cyst of scapula: A rare presentation. AB - Giant cell tumor (GCT) is a distinctive lesion characterized by the proliferation of multinucleate giant cells in a stroma of mononuclear cells; it is generally seen in skeletally mature individuals. GCT of bone is usually found in the long bones around the knee or in the distal radius of young adults and is unusual in the flat bones. We report a case of GCT of the acromion of the scapula, with a secondary aneurysmal bone cyst, in a 30-year-old female. Based on our review of the English language medical literature, it appears that the occurrence of a GCT along with a secondary aneurysmal bone cyst in flat bones (e.g.. the scapula) is very rare. PMID- 20300315 TI - Rupture of the intra-articular portion of the long head of the biceps associated with a symptomatic os acromiale. AB - We report the case of a 45-year-old male who presented with a 5-year history of shoulder pain following an injury. Clinical and radiological investigations revealed a ruptured long head of the biceps and a meso-os acromiale. We performed an arthroscopic resection of the intra-articular stump of the long head of the biceps, followed by internal fixation of the mobile os acromiale using a tension band technique. Rupture of the long head of the biceps associated with a symptomatic os acromiale has not been previously described. This case reinforces the importance of routine shoulder arthroscopy in the treatment of symptomatic os acromiale. PMID- 20300317 TI - An unusual variation of deltoid muscle. AB - An unusual anatomic variation of the deltoid muscle was found in a 45-year-old female cadaver during dissection of the right upper extremity. The posterior fibers of the right deltoid muscle were enclosed in a distinct fascial sheet and the deltoid muscle was seen to arise from the middle 1/3 of the medial border of the scapula. There was no accompanying vascular or neural anomaly of the deltoid muscle. To the best of our knowledge, unilateral posterior separation of the deltoid muscle with a distinct fascia has not been described previously. While dissecting deltoid, posterior deltoid, or scapular flaps, the surgeon needs to look out for this variation because it may cause confusion. PMID- 20300318 TI - Nonunion of a scapular spine fracture: Case report and management with open reduction, internal fixation, and bone graft. AB - Fractures of the scapular spine are relatively uncommon. We report a case of a 39 year old male who developed an atrophic non-union scapular spine fracture entering the spino-glenoid notch. We describe our experience with this rare fracture pattern and identify the need for early internal fixation in the young, active and working population. PMID- 20300319 TI - Giant cell tumor of bone with secondary aneurysmal bone cyst. PMID- 20300320 TI - Separate segments within the deltoid muscle: Anatomical variants or wishful thinking? PMID- 20300321 TI - Isolated focal chondral defects in the glenohumeral joint. PMID- 20300322 TI - Microfracture of chondral lesions of the glenohumeral joint. AB - OBJECTIVE: To determine if microfracture is successful in treating chondral lesions of the shoulder. DESIGN: Case series. SETTING: Tertiary referral practice. PATIENTS: From June 2005 to November 2006, eight patients underwent shoulder arthroscopy with arthroscopic microfracture to treat full-thickness chondral lesions of less than 4 cm(2) size. The study group consisted of six men and two women. The mean age at surgery was 37 years (range: 27-55 years). One patient (12.5%) had an isolated chondral defect and seven patients (87.5%) had associated conditions treated simultaneously: two patients had arthroscopic subacromial decompressions, two had capsular plications for multidirectional instability, and three had anterior stabilization done (one with an associated superior labrum anterior to posterior repair and one with repair of a small rotator cuff tear). Five patients had humeral head defects and three had glenoid defects. INTERVENTION: Microfracture. MAIN OUTCOME MEASURES: Constant score and Oxford score. RESULTS: The mean follow-up period was 15.4 months, with a range of 12-27 months. The mean preoperative Constant score was 43.88 (range: 28-70) and at final follow-up the mean Constant score was 90.25 (range: 85-100); this difference was significant (P<0.005). The mean preoperative Oxford score was 25.75 (range: 12-37) and the mean postoperative Oxford score at final follow-up was 17 (range: 11-27); the difference was significant (P<0.005). There were no complications. Two patients underwent reoperation which allowed assessment of the lesion; in both cases the lesions showed good filling with fibrocartilage. CONCLUSION: Microfracture has been shown to be a reliable method of treatment for chondral lesions within the knee. We believe that this technique may also be applied to the shoulder; however, further study is required to assess its efficacy in this joint. LEVEL OF EVIDENCE: IV. PMID- 20300323 TI - Managing chondral lesions of the glenohumeral joint. PMID- 20300324 TI - Full recovery of muscle function after delayed primary repair of deltoid muscle detachment. AB - Detachment of the deltoid muscle and tendon is a rare complication that is reported to result in poor outcome after rotator cuff surgery. We performed a delayed primary repair of the detached deltoid in a 53-year-old female patient who underwent an open acromioplasty procedure. A successful result was achieved after surgical restoration of the deltoid muscle origin back to the acromion. At 25 months' follow-up the patient had recovered almost the full range of motion of the glenohumeral joint and was free of pain. Due to lack of literature on this rare condition, there are no well-defined treatment principles for the management of deltoid muscle detachments that develop as a complication of rotator cuff surgery. This paper describes a repair procedure for the management of deltoid muscle detachments. In addition, it discusses the importance of the guidelines that have to be followed during primary rotator cuff surgery. PMID- 20300325 TI - Dynamic posterior stabilization of shoulder hemiarthroplasty in long-standing neglected posterior dislocation of the glenohumeral joint. AB - Posterior dislocations of the shoulder are rare. They account for less than 3% of all shoulder dislocations. The treatment of neglected bilateral posterior dislocation of the shoulder is controversial. We present a novel operative technique to stabilize a shoulder hemiarthroplasty that we used in the treatment of a chronic posterior dislocation of a shoulder with an acute four-part fracture of the proximal humerus. PMID- 20300326 TI - Complete absence of the suprascapular notch in a Nigerian scapula: A possible cause of suprascapular nerve entrapment. PMID- 20300327 TI - Message from the president. PMID- 20300328 TI - From the Editor's Desk. PMID- 20300329 TI - An evolution of the "golden age" of dermatologic surgery (1958-2008). PMID- 20300330 TI - Botulinum Toxin: Non-cosmetic Indications and Possible Mechanisms of Action. AB - Botulinum toxin (BTX) has gained a great interest in cosmetic dermatology for its effects on hyperkinetic facial lines. Understanding the basic research and analysis of effects of this potent drug can lead to other possible indications of interest for dermatologists. The use of BTX in focal hyperhidrosis is well established, but BTX has also effects on pain perception, itch and inflammation as discussed in this review. PMID- 20300331 TI - Facial lifting with Aptos Methods. AB - Face lift hitherto had been a complicated and elaborate procedure. The introduction of threads to lift skin has been a major advance in lifting sagging skin. These threads which have barbs on their surface have simplified the procedure and have the possibilities of combination with other rejuvenation procedures. The article traces the evolution of threadlift. PMID- 20300332 TI - A review of modern surgical hair restoration techniques. AB - The field of hair restoration has had a chequered history. From the days of punch grafting to the present day techniques of follicular unit hair transplantation, the field has seen a number of new advances. This article reviews these developments. PMID- 20300333 TI - Serial excision of congenital melanocytic nevi. AB - Congenital melanocytic nevus needs to be excised for aesthetic reasons and concerns regarding its malignant potential. Many methods like surgical resection, dermabrasion, curettage, chemical peeling, laser resurfacing, etc., are available for treatment. We hereby report the efficacy of excision of nevi by serial excision. PMID- 20300334 TI - Co(2) laser resurfacing for facial rhytides. AB - Resurfacing of facial rhytides (periorbital crow-feet wrinkles) was performed in three cases by carbon dioxide laser (Sharplan((R)) 1030 machine). Good to excellent results were observed. However, erythema and postinflammatory pigmentation were important side effects. PMID- 20300335 TI - Treatment of unusually large acrochordon by shave excision and electrodesiccation. AB - Acrochordons are usually small in size and are easily treated with electrofulguration under local anaesthesia. Here is a report of a giant acrochordon which posed problems in management. A technique to manage it under local anaesthesia in an office setting is described. PMID- 20300336 TI - Combination treatment of periungual warts. AB - Periungual wart presents challenge for management in view of their frequent recurrence. The case report demonstrates the efficacy of a combination treatment of electrodessication and trichloroacetic acid application. PMID- 20300337 TI - Modified Unna Boot and Pinch Grafting for Chronic Non-healing Venous Leg Ulcer. AB - Venous ulcers cause considerable morbidity. A 45-year-old man reported with non healing ulcer since 15 years. Patch tests revealed multiple sensitivity. Infection was first controlled with antibiotics and antiseptics. Dressing with modified Unna's boot made with zinc oxide 40% and glycerine paste 60% resulted in formation of healthy granulation tissue. Pinch grafting was subsequently done to promote epithelization. We recommend the use of Unna's paste instead of more expensive synthetic and occlusive and semi occlusive dressing to promote granulation tissue and pinch grafting after bed is ready to hasten epithelization. PMID- 20300338 TI - Radiosurgical ablation of solitary trichoepithelioma. AB - Trichoepithelioma presents a challenge for management in view of its location. We describe the use of radiofrequency ablation in the management of this condition. PMID- 20300339 TI - Excision of Basal cell carcinoma with radio frequency ablation. AB - Basal cell carcinoma is usually treated by excision, or by ablative methods such as cryosurgery and laser. We describe treament of basal cell carcinoma by radiofrequency device. PMID- 20300341 TI - Informed consent: an ethical obligation or legal compulsion? AB - Informed consent is a vital document while performing all surgical and aesthetic procedures, particularly in the current day practice. Proper documentation and counseling of patients is important in any informed consent. PMID- 20300340 TI - Split skin grafting for leg ulcers complicating rheumatoid arthritis. AB - Leg ulcers as a complication of rheumatoid arthritis are difficult to heal. We present a case responding to treatment with cyclophosphamide and split skin grafting. PMID- 20300342 TI - Use of Injection Five Fluorouracil (FFU) With or Without Injection Trimacinolone in the Management of Hypertrophic Scars and Keloids. PMID- 20300343 TI - How to make local anesthesia less painful. AB - Most cutaneous surgeries are performed under local anaesthesia. It is important the process of administration of local anaesthetics is pain free. This article suggests simple tips to make local anaestesia less painful. PMID- 20300344 TI - Tumescent liposuction: a review. AB - Liposuction is a cosmetic procedure to remove fat. Liposuction may be performed either under general anaesthesia or under local anaesthesia. The procedure has been reported to be associated with significant morbidity and risk of mortality under general anaesthesia. Since the first description by Jeffrey Klein, dermatologic surgeons have made significant contributions in this field, and tumescent liposuction using microcannuale under local anaesthesia, is regarded as safe and effective. The author has performed over 200 liposuctions in the last four years in India and this article describes the procedure of microcannular tumescent liposuction in the light of her experience. PMID- 20300345 TI - Pharmacological sphincterotomy for chronic anal fissures by botulinum toxin a. AB - Chronic anal fissure is a common proctologic disease. Botulinum toxin (BTX) can be used for temporary chemical denervation to treat this painful disorder. Its application is by intramuscular injections into either the external or internal anal sphincter muscle. The mode of action, application techniques, and possible complications or adverse effects of BTX therapy are discussed in this report. The healing rate is dependent on the BTX dosage. The short-term healing rate ( 1 year). Adverse effects are generally mild, but relapses occur more often than with surgery. Conservative therapy is currently considered as a first-line treatment. With increasing evidence for its efficacy, BTX can now be considered among the first-line nonsurgical treatements. Although, surgical management by lateral sphincterotomy is the most effective treatment, it shows a higher incidence of incontinence and greater general morbidity rate than BTX. BTX is a useful alternative to surgery and in many cases, surgery can be avoided with the use of BTX. PMID- 20300346 TI - Dermal fillers: tips to achieve successful outcomes. AB - Fillers have become a common aesthetic treatment for several cosmetic problems. Several types of fillers are available from different sources and of different longevities. It is important that the treating physician be aware of the different techniques of administration and their possible side effects. This article reviews the available literature on the subject. PMID- 20300347 TI - Teledermatology: its role in dermatosurgery. AB - Dermatologic surgery and aesthetic dermatology are rapidly emerging and expanding specialties in India. However, dermatologists practicing surgeries and aesthetics in India represent a highly selected group and are mostly confined to metros. Dermatologists in the peripheral and remote regions need to reach these specialists for the benefit of their patients and teledermatology is an invaluable tool for this purpose. Video-conference, store and forward, Satellite communication, Hybrid teledermatology, mobile teledermatology, Integration model, nurse-led teledermatology, teledermatology focusing difficult-to-manage cases, screening and triage services are the various teledermatology services developed to suit the needs of dermatology care from a distance. Types of teledermatology service, pattern of net work connectivity and purpose of dermatology service are the three cardinal parameters for management of the dermatoses from a distance. This article reviews the literature, and analyzes the possible options available for a teledermatosurgery practice. PMID- 20300348 TI - Evaluation of Long-pulsed 1064 nm Nd:YAG Laser-assisted Hair Removal vs Multiple Treatment Sessions and Different Hair Types in Indian Patients. AB - BACKGROUND: LONGER WAVELENGTH LASERS SUCH AS ND: YAG are considered to be the best for darker skin phototypes. OBJECTIVES: The aim of this study was to investigate the safety and efficacy of long-pulsed, 1064 nm Nd:YAG laser-assisted hair removal in relation to multiple treatment sessions and different hair types in Indian patients. METHOD: Fifty-nine adult women with skin phototypes IV and V were treated with a long-pulsed Nd: YAG laser (1064 nm, 10 mm spot size, fluence of 30-50 J/cm(2), pulse duration 15-30 ms). Six consecutive treatment sessions were given at 4-6 week intervals. The modified Ferriman Gallway system of scoring was used to grade the hairs before each treatment session and six weeks after the last therapy. Based on this grading, three main hair types were recognised: thin vellus (Grade 1), intermediate (Grade 2), and terminal hair (Grades 3 and 4). Patients were divided into three groups: achievers who converted to thin vellus hair (Grade I), responders who shifted to a lower grade but were short of reaching grade 1, and failures who did not show any change throughout the six laser sessions. RESULTS: Six weeks after six laser treatment sessions, the achievers totaled 56%, responders 23%, and failures 20% of the patient population. At the end of the 3(rd), 4(th), 5(th), and 6(th) sessions, achievers were 5, 15, 25, and 56% respectively of all the patients (P < 0.001, which was statistically significant). Achievers for terminal hair were 57.5% while it was 53.8% for intermediate hair (P = 0.9, nonsignificant). There were no permanent side effects. There were no failures in the terminal group while nearly 50% of the patients were failures in the intermediate group. CONCLUSION: Six multiple laser treatment sessions with a long-pulsed, 1064 nm Nd: YAG laser with contact cooling were found to be safe and effective for hair reduction in Indian patients with both terminal and intermediate hair. The success rate was found to improve with successive sessions. However, terminal hairs responded better than intermediate hairs. PMID- 20300349 TI - QYAG5 Q-switched Nd:YAG Laser Treatment of Nevus of Ota: An Indian Study of 50 Patients. AB - BACKGROUND: Nevus of Ota is very common in Asian patients. The condition is more common in females, with a male-female ratio of 1:4.8. Most patients seek treatment early in life due to the psychological trauma and cosmetic disfigurement. The Q-switched lasers have changed the way we approach the condition and have become the mainstay of therapy. AIMS AND OBJECTIVES: To evaluate long-term safety and efficacy of pigmented lesion laser Palomar QYAG5 Q switched Nd:YAG in 50 Indian patients. MATERIALS AND METHODS: Fifty patients of nevus of Ota underwent multiple treatments (average 6 sessions) carried out over a period of 1year with a Q-switched Nd:YAG laser (QYAG5, Palomar, USA). Of the 50 patients, 2 were males; and the rest, females. Five patients had a bilateral involvement. Skin types treated included phototypes 4 and 5. The response after subsequent treatments was documented through serial photographs that were taken before and after the completion of treatments. Patients were followed up for a period of 1 year after the last session. Response to treatment was graded based on physician's global assessment. RESULTS: Excellent improvement was noted in a majority of the patients at the end of the treatments. Greater-than-60% improvement was seen in 66% of the patients. The remaining patients had moderate clearing of pigmentation (30%-60% improvement). No significant adverse effects were seen immediately after the treatments and on long-term follow-up. Transient post-inflammatory hyperpigmentation was observed in 5 (10%) patients, which cleared with use of sunscreens and bleaching agents within 2 months. No textural change or scarring was seen. Hypopigmentation (guttate type) was observed in 1 (2%) patient, which resolved within 3 months. No recurrence was observed after 1 year of follow-up. CONCLUSION: This study validates the superior efficacy of Q switched Nd:YAG laser when compared to conventional methods for treatment of nevus of Ota. PMID- 20300350 TI - Lymphangioma circumscriptum (microcystic lymphatic malformation): palliative coagulation using radiofrequency current. AB - Lymphangioma circumscriptum (LC, microcystic lymphatic malformation), a hamartomatous lymphatic malformation, is a difficult condition to treat. Different treatments such as surgical excision, lasers, sclerotherapy etc have all been tried with varying success. We report here the efficacy of a radiofrequency current in two patients with lymphangioma circumscriptum. The radiofrequency technique is a safe, economical, and commonly available technique for the treatment of LC; the surgical safety and outcome were satisfactory in our patients. PMID- 20300351 TI - Radiofrequency ablation of adenoma sebaceum. AB - Adenoma sebaceum is one of the diagnostic features of tuberous sclerosis. Histologically, they are angiofibromas that occur over the central part of the face and hence, cause a major cosmetic disfigurement. Different forms of ablative treatments including laser ablation have been used for the treatment of this condition. Laser treatment is expensive and any form of treatment for adenoma sebaceum is not a one-time procedure but is a recurring process as the condition is genetic in aetiology. It is therefore appropriate to use a cheap and easily available modality, particularly in the Indian scenario. We hereby report a case of tuberous sclerosis in whom we ablated the lesions by radiofrequency technique with acceptable results. PMID- 20300352 TI - Hailey-hailey disease: a novel method of management by radiofrequency surgery. AB - Hailey-Hailey disease is a chronic, recurrent disease that causes considerable morbidity to the patient. While the medical line of treatment is only palliative, different surgical modalities have been reported to offer longer lasting remission. We report a case of Hailey-Hailey disease successfully treated with radiofrequency surgery. PMID- 20300353 TI - Radiofrequency in dermatosurgery. PMID- 20300354 TI - Botulinum Toxin Deaths: What is the Fact? PMID- 20300356 TI - Lawrence M Field's article on "An evolution of the 'Golden Age' of dermatological surgery (1958-2008)" and my views. PMID- 20300355 TI - Evaluation of Speakers at CME: Cosmecon 2006, An International Conference on Ageing and Anti-ageing. AB - AIM: To determine what constitutes effective or ineffective lecturing in dermatological conferences and also the utility of a scientific programme for the dermatologists. METHODS AND MATERIALS: Evaluation forms were circulated to delegates attending the Cosmecon conference on ageing and anti-ageing, held in July 2006 at Bangalore. Feedback from the delegates in the form of completed evaluation forms of individual speakers and each session of the 3-day conference Cosmecon (including the live workshop on aesthetic and surgical procedures) were studied. Comments were analysed with the help of a biostatistician to determine the positive and negative responses. RESULTS: On day 1 of the conference, workshop included 14 procedures by different specialists and on the second and third days of the conference, there were a total of 10 sessions, with five on each day. Evaluation forms were handed out to 440 delegates on day 1 and 600 delegates on days 2 and 3. Fifty-five speakers were evaluated by an average 56 delegates out of 440 delegates on day 1 and 600 delegates on the second and third days. The delegate response to completing the evaluation form was poor. Only about 25% of the delegates completed the feedback forms. However, the feedback did give some insight to the scientific programme, on both positive and negative aspects. Most delegates stated that they benefited from the presentations. The main negative response was lack of opportunity to ask questions after a lecture. The main positive comment was that the time keeping in the conference was very good. CONCLUSION: The response of the delegates in providing feedback was poor. Efforts have to be made to educate and encourage delegates to complete the feedback forms. Systematic review of the speakers would provide information to design future CME programmes effectively and to incorporate improvements for effective lecturing and to avoid ineffective lectures. The CME evaluation can also help the organizers to provide training to presenters and to monitor performance. PMID- 20300357 TI - (Great) Grandfatherly Advice for Young(er) Dermatologic Surgeons. PMID- 20300358 TI - Modified subcuticular stitch. PMID- 20300359 TI - Techniques of skin biopsy and practical considerations. AB - Skin biopsy is a safe, easy and out-patient procedure of diagnostic and academic relevance. There are various methods of performing skin biopsy depending on the size of lesion, suspected clinical diagnosis and site of lesion. Although biopsy is usually a safe procedure, complications such as bleeding, infection and scarring may occasionally be encountered while performing biopsy in an out patient with basic infrastructure. This article details the various techniques of skin biopsy, their indications and practical steps to curtail complications arising from the procedure. PMID- 20300360 TI - Use of Lasers for Becker's Nevus and Keratosis Pilaris. PMID- 20300362 TI - Checklists for surgical safety in dermatosurgery. PMID- 20300363 TI - Controversy: botulinum toxin in pregnancy. AB - Botulinum toxin A (BTX-A), a purified protein derived from the bacteria Clostridium botulinum, has been widely used in aesthetic dermatology. Though BTX A was initially used by neurologists extensively for neurological conditions such as blepharospasm, strabismus headaches, dystonia and spasticity, it has become popular among dermatologists and plastic surgeons for its cosmetic indications. Its use in pregnancy has been controversial and this article deals with the issues of use of BTX-A in pregnancy. PMID- 20300364 TI - Blepharoplasty: an overview. AB - Blepharoplasty plays a vital role in facial rejuvenation, with direct aesthetic relation to the brow and the cheek. Upper and lower eyelid blepharoplasty are indicated for the treatment of excess skin and/or orbital fat. Preoperative evaluation should include a thorough medical and ophthalmic history, along with a detailed cutaneous and eye examination. Symptoms of preexisting dry eye should be elicited preoperatively, as they directly correlate with postoperative complications. Physical examination should take into account brow position, eyelid ptosis, lower eyelid position, and cheek projection. Blepharoplasty can be performed by many operative approaches. This review highlights the standard skin only upper blepharoplasty and lower eyelid conservative fat excision or repositioning. PMID- 20300365 TI - Finasteride-its impact on sexual function and prostate cancer. AB - Finasteride, a specific and competitive inhibitor of 5alpha-reductase enzyme Type 2, inhibits the conversion of testosterone to dihydrotestosterone (DHT). In adults, DHT acts as primary androgen in prostate and hair follicles. The only FDA approved dermatological indication of finasteride is androgenetic alopecia. But, apprehension regarding sexual dysfunction associated with finasteride deters dermatologists from prescribing the drug and patients from taking the drug for androgenetic alopecia. Testosterone, through its humoral endocrine and local paracrine effects is relevant in central and peripheral modulation of sexual function than locally acting DHT. Several large population-based long-term placebo-controlled studies, using International Index of Erectile Function-5 questionnaire and objective method (Nocturnal Penile Tumescence) to assess the erectile function have demonstrated no clear evidence of the negative effect of finasteride on erectile function. Reduction in ejaculatory volume is the only established causal relationship between finasteride and sexual dysfunction. Though finasteride causes significant reduction in all the semen parameters except sperm morphology, they did not fall below the threshold levels to interfere with fertility. Therefore, the sexual adverse effects associated with finasteride should be viewed in relation to normal prevalence and natural history of erectile dysfunction in the population, age of the patient, other confounding factors and also nocebo effect. The impact of finasteride on the prevention of prostate cancer has been discussed extensively. Finasteride is found to be effective in significantly reducing the incidence of low-grade prostate cancer. But the paradoxical increase in high-grade cancer in the finasteride group has been attributed to increased sensitivity and improved performance of prostate specific antigen levels to detect all grades of prostate cancer. PMID- 20300366 TI - Peat: a natural source for dermatocosmetics and dermatotherapeutics. AB - In recent years the interest for natural substances in dermatotherapy and cosmetics has increased. Peat is a complex natural source of humic substances that are of potential interest in both dermatology and cosmetology. Humic substances in peat have been partially characterized and pharmacologic and biologic activities have been documented. Possible clinical applications are outlined. PMID- 20300367 TI - Soft tissue augmentation with autologous fat graft: the dissected pouch technique. AB - BACKGROUND: Soft tissue augmentation with autologous fat graft has been increasingly used by plastic surgeons despite unpredictable results. Several techniques have been described to prevent the main setback of this technique, fat graft resorption. However, there is no ideal technique described for this purpose. MATERIALS AND METHODS: Twenty patients with subcutaneous tissue loss, atrophy or hypoplasia were treated with lipofilling. A subcutaneous pouch is dissected at the deformed area and later it is filled with autologous fat graft. RESULTS: Graft maintenance during the postoperative period was satisfactory. Overcorrection was not performed except for the first three cases. Patient, surgeon and layman satisfaction was surveyed. Satisfaction was rated between 0 and 10. The mean score was 7.67 +/- 1.22. CONCLUSION: The authors describe a technique for soft tissue augmentation which effectively corrects contour deformities, provides a low resorption rate and a relatively non-visible scar without causing irregularities. PMID- 20300368 TI - Microneedling therapy in atrophic facial scars: an objective assessment. AB - BACKGROUND: Atrophic facial scars are always a challenge to treat, especially the ones that are deep-seated and/or involve much of the face. Microneedling or dermaroller therapy is a new addition to the treatment armamentarium for such scars that offers a simple and reportedly effective management of these scars. AIMS: The aim of the present study was to perform an objective evaluation of the efficacy of dermaroller treatment in atrophic facial scars of varying etiology. MATERIALS AND METHODS: Thirty-seven patients of atrophic facial scarring were offered multiple sittings of microneedling (dermaroller) treatment and their scars were evaluated and graded clinically and by serial photography at the start as well as at two months after the conclusion of the treatment protocol. Any change in the grading of scars after the end of treatment and follow-up period was noted down. The patients were also asked to evaluate the effectiveness of the treatment received on a 1-10 point scale. The efficacy of dermaroller treatment was thus assessed both subjectively by the patients as well as objectively by a single observer. RESULTS: Overall 36 out of the total of 37 patients completed the treatment schedule and were evaluated for its efficacy. Out of these 36 patients, 34 achieved a reduction in the severity of their scarring by one or two grades. More than 80% of patients assessed their treatment as 'excellent' on a 10 point scale. No significant adverse effects were noted in any patient. CONCLUSIONS: Microneedling therapy seems to be a simple and effective treatment option for the management of atrophic facial scars. PMID- 20300369 TI - Serenoa Repens: Does It have Any Role in the Management of Androgenetic Alopecia? AB - Serenoa repens is one among the many naturally occurring 5 alpha reductase (5aR) inhibitors which has gained popularity as a magical remedy for androgenetic alopecia. It is widely advertised on the web and sold by direct marketing. Used as a self-medication, there is a risk of missing the early detection of prostate cancer. There is little evidence to support its efficacy, warranting larger clinical trials on androgenetic alopecia. PMID- 20300370 TI - Combination technique of radiofrequency ablation with sclerotherapy in acquired lymphangiectasis of the vulva. AB - Aquired lymphangiectasis of the vulva is an uncommon condition and only few cases have been reported following tuberculous lymphadenitis. A case is reported that was successfully treated with a unique combination therapy of radiofrequency ablation and sclerotherapy with polidocanol. There was no recurrence at two years of follow-up. PMID- 20300371 TI - Pilomatrixoma of earlobe. AB - Pilomatrixomas are uncommon in children and are frequently misdiagnosed preoperatively. We report a two-year-old female patient with an unusual localization in the earlobe. The lesion was treated by simple enucleation and in two years of follow-up there has been no evidence of recurrence. The case is being reported in view of its rarity and unusual location. PMID- 20300373 TI - Stability in vitiligo: why such a hullabaloo? PMID- 20300372 TI - Stability in Vitiligo? What's that? PMID- 20300375 TI - Definitions in laser technology. PMID- 20300374 TI - A painless nodule with excessive sweating. PMID- 20300376 TI - Conference Report: ACSICON 2008. PMID- 20300377 TI - Cutaneous vesicles caused by transcutaneous gas-monitoring sensor. PMID- 20300378 TI - The philosophy we believe and the principles we practice. PMID- 20300379 TI - State of the Globe: Yellow Fever is Still Around and Active! PMID- 20300380 TI - Assessing yellow Fever risk in the ecuadorian Amazon. AB - This study reports results of a cross-sectional study based on interviews and seroepidemiological methods to identify risk factors for yellow fever infection among personnel of a military garrison in the Amazonian rainforest. Clinical symptoms and signs observed among yellow fever cases are also described. Humoral immune response to yellow fever, Mayaro, Venezuelan equine encephalitis, Oropouche, and dengue 2 infection was assessed by evaluating IgM and IgG specific antibodies. A yellow fever attack rate of 13% (44/341, with 3 fatal cases) was observed among military personnel. Signs of digestive track bleeding (14.6%) and hematuria (4.9%) were observed among the yellow fever cases. In 32.2% of the cases, we measured high levels of serum glutamic oxaloacetic transaminase and serum glutamic pyruvic transaminase with maximum levels of 6,830 and 3,500, respectively. Signs of bleeding or jaundice were observed in some cases, and high levels of transaminases were seen. The epidemiological and laboratory investigations demonstrated that the military personnel were affected by a yellow fever outbreak. The association between clearing the rainforest and also being at the detachments with yellow fever infection confirms that clearing is the main factor in the jungle model of transmission, which takes place deep in the Amazonian rainforest. PMID- 20300382 TI - HIV Infection, Genital Symptoms and Sexual Risk Behavior among Indian Truck Drivers from a Large Transportation Company in South India. AB - BACKGROUND: Sentinel surveillance conducted in the high Human Immuno-deficiency Virus (HIV) prevalent state of Andhra Pradesh includes sub-populations thought to be at high-risk for HIV, but has not included truck drivers. Novel HIV prevention programs targeting this population increasingly adopt public - private partnership models. There have been no targeted studies of HIV prevalence and risk behavior among truck drivers belonging to the private sector in India. METHODS: A sample of 189 truck drivers, aged between 15 and 56, were recruited from Gati Limited's large trucking depot in Hyderabad, India. A quantitative survey instrument was conducted along with blood collection for HIV 1/2 testing. Multivariate regression models were utilized to determine predictors of HIV infection and risk behavior. RESULTS: 2.1% of subjects were infected with HIV. Older age was protective against self-reported genital symptoms (OR = 0.77; P = 0.03), but these were more likely among those truck drivers with greater income (OR = 1.05; P = 0.02), and those who spent more time away from home (OR = 25.7; P = 0.001). Men with higher incomes also reported significantly more sex partners (OLS coefficient = 0.016 more partners / 100 rupees in monthly income, P = 0.04), as did men who spent a great deal of time away from home (OLS coefficient = 1.30, P = 0.002). Drivers were more likely to report condom use with regular partners if they had ever visited a female sex worker (OR = 6.26; P = 0.002), but married drivers exhibited decreased use of condoms with regular partners (OR = 0.14, P = 0.008). Men who had higher levels of knowledge regarding HIV and HIV preventative practices were also more likely to use condoms with regular partners (OR = 1.22, P = 0.03). CONCLUSION: Time away from home, urban residence, income, and marital status were the strongest correlates of genital symptoms for Sexually Transmitted Infections (STI) and risk behaviors, although none were consistent predictors of all outcomes. Low HIV prevalence might be explained by a cohort that was mostly married, and at home. Novel HIV prevention interventions may be most cost effective when focusing upon young, single, and long-haul truck drivers. PMID- 20300381 TI - Two Highly Immunized Hilly Areas versus Double Measles Outbreak Investigations in District Kangra, Himachal Pradesh, India, in 2006. AB - BACKGROUND: We investigated two sequential outbreaks of measles in seven villages of Kangra, to confirm the diagnosis and to formulate recommendations for prevention and control. METHODS: We defined a case of measles as occurrence of fever with rash in a child aged six months to 17 years during the period 3(rd) September to 23(rd) November 2006. We collected information on age, sex, residence, date of onset, symptoms, signs, treatment taken, traveling history and vaccination status. We described the outbreak by time, place and person. We estimated vaccine coverage and efficacy in the affected villages. We confirmed diagnosis clinically, serologically and through genotyping of the virus. RESULTS: We identified 69 cases. Overall attack rates ranged between 4.2% and 6%. All case patients were between 6 years to 11 years of age. Age-specific attack rate in double outbreaks ranged in between 1.7% and 21.6%, the highest being in the age range 11-17 years. No deaths or complications were reported. The epidemic curve was suggestive of typical propagated pattern. The first outbreak imported virus after an interschool game competition (relative risk, 6.44%; 95% confidence interval, 3.81-10.91); followed by the second outbreak, in which people exchanged foods in the festival in one infected village of the first outbreak (relative risk, 5.3; 95% confidence interval, 1.90-14.77; P <.001). The calculated immunization coverage (93%) coincided nearly with administrative claims. The vaccine efficacies were estimated to be 85% and 81% in the first and second outbreaks respectively. Eleven of the 16 case patients were tested for measles IgM antibodies, while two nasopharyngeal swabs were positive by polymerase chain reaction (PCR) and are genotyped D4 measles strain. Vitamin A supplementations were only given in four villages. CONCLUSION: Measles outbreaks were confirmed in high-immunization-coverage areas. We recommended (i) second dose opportunity for measles in Himachal Pradesh and (ii) vitamin A supplementation to all the case patients. PMID- 20300383 TI - Clinical significance of isolated anti-hbc positivity in cases of chronic liver disease in new delhi, India. AB - BACKGROUND: The presence of anti-HBc IgG in the absence of HBsAg is usually indicative of a past self-limiting HBV infection. But it is frequently associated with co-infection with HCV which can worsen the existing status of chronic liver disease (CLD). OBJECTIVES: The present study was planned to evaluate the significance of isolated HBc IgG positivity in patients of CLD and look for the presence of HCV co-infection in such patients. METHODS: Clinical profiles and biochemical tests were done for all the 77 CLD cases included in the study. Blood samples were taken from these patients and tested by the commercially available EIA for the presence of HBsAg, anti-HBc IgG, anti-HBs and anti-HCV. HBV DNA was detected by amplifying the surface region in all the cases. RESULTS: Isolated anti-HBc IgG positivity defined as the presence of anti-HBc IgG in absence of any other serological markers of HBV infection was detected in 28 patients. Out of 64 patients positive for anti-HBc IgG 36 had the markers of HBV, either HBsAg, HBV DNA or anti-HBs alone or in combination. There was a significant association between isolated anti-HBc IgG positivity and HCV co-infection. CONCLUSION: Anti HBc IgG should be tested in all patients with CLD as it is frequently the only marker of HBV infection in such patients and they should be monitored closely as such patients can develop CLD. Presence of co-infection with HCV should be actively searched for in such patients. PMID- 20300385 TI - The laboratorial diagnosis of dengue: applications and implications. AB - The diagnosis of infection by the dengue virus relies, in most cases, on the clinical judgment of the patient, since only a few major centers have clinical laboratories that offer diagnostic tests to confirm the clinical impressions of an infection. At present, routine laboratory diagnosis is done by different kinds of testing. Among them are the methods of serological research, virus isolation, detection of viral antigens, and detection of viral genomes. The continued development of diagnostic tests, which are cheap, sensitive, specific, easy to perform, and capable of giving early diagnosis of the dengue virus infection is still a need. There are also other obstacles that are not specifically related to the technological development of diagnostic methods. For instance, infrastructure of the laboratories, the training of personnel, and the capacity of research of these laboratories are still limited in many parts of Brazil and the world, where dengue is endemic. Clinical laboratories, especially the ones that serve regions with a high incidence of dengue, should be aware of all the diagnostic methods available for routine these days, and choose the one that best suit their working conditions and populations served, in order to save lives. PMID- 20300384 TI - Association between hepatitis C and hepatocellular carcinoma. AB - Hepatocellular carcinoma (HCC) is the fifth most common cancer, the third most common cause for cancer death in the world, a major cause of death in patients with chronic hepatitis C virus infection, and responsible for approximately one million deaths each year. Overwhelming lines of epidemiological evidence have indicated that persistent infection with hepatitis C virus (HCV) is a major risk for the development of HCC. The incidence of HCC is expected to increase in the next two decades, largely due to hepatitis C infection and secondary cirrhosis, and detection of HCC at an early stage is critical for a favorable clinical outcome. Potential preventive strategies in the development of HCC are being recognized. The natural history of HCC is highly variable and the clinical management choices for HCC can be complex, hence patient assessment and treatment planning have to take the severity of the nonmalignant liver disease into account. This review summarizes the inter-relationship between HCV and liver carcinogenesis. PMID- 20300386 TI - Staphylococcal scalded skin syndrome in a newborn. AB - A six-day-old newborn was admitted with exfoliating erythematous lesions over the face, of two days duration. The lesions spread to the rest of the body during the next two days. A diagnosis of Staphylococcal Scalded Skin Syndrome (SSSS) was made clinically and confirmed by isolation of Staphylococcus aureus from a blood sample. The child responded to Injection vancomycin and no fresh lesions were seen after the next 48 hours. However the child developed severe pneumonia and left against medical advice. PMID- 20300387 TI - Herpes labialis manifesting as recurrent erythema multiforme and solitary ulcer on face. AB - A 65-year-old lady presented with recurrent crusting of lips and ulceration on face since the last three weeks. History revealed recurrent herpes labialis during the previous three years. Examination showed hemorrhagic crusting of lips and a solitary crusted ulcer on the right cheek. The patient showed partial improvement with antiviral therapy. On withdrawal of initial therapy, the patient developed classical lesions of herpes labialis and erythema multiforme. Investigations confirmed herpes simplex infection and erythema multiforme. All the lesions including the ulcer on the face responded to maintenance therapy with antivirals. Though herpes infection has been found to cause ulcers especially in the peri-anal region in immunosuppressed individuals, it is the first time in literature that a facial ulcer has been ascribed to herpes simplex virus that too in an immunocompetent individual. PMID- 20300388 TI - Seasonal influenza: waiting for the next pandemic. AB - With the ongoing cases of H1N1 influenza (aka Swine Flu) occurring around the globe, seasonal influenza has a tendency to be overlooked by the media and general population as a source of illness and death. Yet, these pandemic influenza viruses arise from these seasonal influenza viruses. This article will provide an overview of seasonal influenza, its prevention and treatment, and the global surveillance system in place, used to detect the next influenza pandemic. PMID- 20300389 TI - Approach to a patient with urosepsis. AB - Urinary tract infections can occur in all age groups and produce an exceptionally broad range of clinical syndromes ranging from asymptomatic bacteriuria to acute pyelonephritis with Gram negative sepsis to septic shock. In approximately one quarter of all patients with sepsis, the focus of infection is localized to the urogenital tract. This may lead to substantial morbidity and significant economic implications. We present a review of the current approaches to managing urospesis. PMID- 20300390 TI - Histological diagnosis of madura foot (mycetoma): a must for definitive treatment. AB - Mycetoma, an uncommon chronic infection of skin and subcutaneous tissues in tropical countries is caused by true fungi (eumycetoma) or by filamentous bacteria (actinomycetoma). Since the treatment of these two etiologies is entirely different, a definite diagnosis after histopathological and microbiological examination is mandatory. We hereby present five cases of Madura foot. PMID- 20300391 TI - Fatal Postoperative Candida glabrata Septicemia in a Child with Congenital Heart Disease. AB - The incidence of candidemia has been reported to be high in some cardiovascular surgery units. Congenital heart disease has been considered a risk factor for acquisition of candidemia. This present case is a postoperative Candida glabrata in a child with congenital heart disease. A 3-year-old child, a previously diagnosed case of situs-solitus D loop situs with double outlet right ventricle, ventricular septal defect, pulmonary stenosis and large ostium secundum atrial septal defect, was admitted with history of effort intolerance. A left modified Blalock-Taussig shunt was performed and then the child underwent closure of the ventricular septal defect and the atrial septal defect. On the third day the patient developed fever. Klebsiella pneumoniae was isolated from blood which responded to piperacillin + tazobactam but on the twelfth day, the patient again developed fever spikes. The blood cultures performed at this time showed repeated isolation of Candida glabrata. Amphotericin B was started but still the patient deteriorated and died on the 22(nd) day after operation. The antifungal susceptibility of the isolate performed showed that the isolate was resistant to Amphotericin B. PMID- 20300392 TI - A case of endogenous trichosporon endophthalmitis treated with micafungin and voriconazole. AB - Invasive fungal infections are a significant cause of morbidity and mortality. Endogenous fungal endophthalmitis is a rare intraocular infection with potential vision threatening consequences. Our review of the literature revealed only one other case of Trichosporon endophthalmitis. Ocular fungal infections are difficult to eradicate because of the limited availability of systemic and intravitreal therapeutic agents and poor tissue penetration of current antifungals. Along with systemic antifungal agents, vitrectomy and intravitreal amphotericin B have been suggested as optimal treatments for fungal endophthalmitis. Other antifungals such as flucytosine and triazoles have recently received consideration. Although the current antifungal therapy is not highly successful, there remains a significant potential for more successful treatments in the future, based on the current studies. We report a case of endogenous trichosporon endophthalmitis that was successfully treated with micafungin and voriconazole. This combination has not been previously reported as a successful therapy in literature. More targeted research is required to uncover additional efficacious therapies to combat trichosporon. PMID- 20300393 TI - Cholera outbreaks in iran and duration time of outbreaks. PMID- 20300394 TI - Inducible Clindamycin Resistance in Staphylococcus aureus: Reason for Treatment Failure. PMID- 20300395 TI - Cytomegalovirus infection and unusual early graft dysfunction in a renal transplant recipient. PMID- 20300396 TI - State of the globe: evaluating the existence of extended spectrum Beta lactamases. PMID- 20300397 TI - Extended Spectrum Beta-lactamase Detection in Gram-negative Bacilli of Nosocomial Origin. AB - BACKGROUND: Resistance to third generation cephalosporins by acquisition and expression of extended spectrum beta lactamase (ESBL) enzymes among gram-negative bacilli is on a rise. The presence of ESBL producing organisms significantly affects the course and outcome of an infection and poses a challenge to infection management worldwide. MATERIALS AND METHODS: In the period from June 2007 to 2008, we collected 1489 samples from patients suspected of nosocomial infection. The isolates were identified based on colony morphology and biochemical reaction. Gram negative bacilli resistant to third generation cephalosporins were tested for ESBL by double disc synergy test (DDST- a screening test)and then phenotypic confirmatory test. Antimicrobial susceptibility testing was done by modified Kirby Bauer disc diffusion method. RESULTS: From the sample of 238 gram-negative bacilli, we isolated Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, Citrobacter freundii, Proteus mirabilis, Morganella morganii and Enterobacter cloacae. Following both methods, 34% isolates were ESBL-positive. The ESBL producing isolates were significantly resistant (p < 0.01) to ampicillin, piperacillin, piperacillin/tazobactam, trimethoprim/sulfamethoxazole, tetracycline, ciprofloxacin and gentamicin as compared to non-ESBL producers. Multidrug resistance was significantly (p < 0.01) higher (69.14%) in ESBL positive isolates than non-ESBL isolates (21.66%). CONCLUSION: High prevalence of ESBL in our hospital cannot be ignored. ESBL producers can be detected by DDST and phenotypic confirmatory test with equal efficacy. The sensitivity of screening test improved with the use of more than one antibiotic and addition of one or two antibiotics would not increase cost and labor. We recommend DDST using multiple antibiotics in all microbiology units as a routine screening test. PMID- 20300398 TI - Current Status of HIV/AIDS in South Asia. AB - BACKGROUND: According to the United Nations Joint Program on HIV/AIDS, 33.2 million adults and children are living with the infection worldwide. Of these, two to three million are estimated to be in South Asia. All countries of the region have a low prevalence of human immunodeficiency virus (HIV). However, it is important to review the current epidemiological data to identify the trends of infection as it would have implications on prevention. MATERIALS AND METHODS: We performed a MEDLINE search using phrases 'South Asia' plus 'HIV', 'AIDS', and names of individual countries in South Asia (limits: articles published in last 10 years, in English language). Clinical trials, reviews, meta-analyses, letters, editorials, and practice guidelines were all considered. The following countries were included as belonging to South Asia; Afghanistan, Bangladesh, Bhutan, India, Maldives, Nepal, Pakistan and Sri Lanka. Recent estimates and data on country status, and details of national control programs were obtained from websites of international agencies such as the World Bank and United Nations Joint Program on HIV/AIDS (UNAIDS). RESULTS AND DISCUSSION: This review looks into many aspects of HIV infection in South Asia including country profiles with regard to infection, economic and psychological burden of illness and treatment issues in the South Asian context. PMID- 20300399 TI - Insecticides Susceptibility Status of the Bedbugs (Cimex lectularius) in a Rural Area of Magugu, Northern Tanzania. AB - The recent spread of bedbugs, Cimex lectularius L. (Heteroptera: Cimicidae), has received attention of the public health sector for designing of effective plan of action for control. Several studies have focused on determining the distribution and abundance of bedbug populations in tropical areas. This study establishes baseline information on deltamethrin, permethrin, alphacypermethrin, lambdacypermethrin and K-O tab susceptibility status in a bedbug population collected from Magugu area in northern Tanzania. The evolution of insecticide resistance could be a primary factor in explaining this resurgence of bedbugs in many areas, both rural and urban. Evaluation of the bedbug population from houses in Magugu indicates that the population of bedbugs is susceptible to pyrethroid insecticides, which are commonly used. Without the development of new tactics for bedbug resistance management, further escalation of this public health problem should be expected when resistant gene spreads within the population. These results suggest that although all concentrations kill bedbugs, more evaluations should be done using WHO kits and mechanisms involved in pyrethroid resistance should be evaluated, such as metabolic and knockdown resistance gene, to have a broad picture for better design of control methodologies. PMID- 20300400 TI - Antibiotic Sensitivity and Plasmid Profiles of Escherichia coli Isolated from Pediatric Diarrhea. AB - BACKGROUND: The emergence of drug resistance among diarrheagenic Escherichia coli (E. coli) in the pediatric population is an important cause of morbidity and mortality in developing countries. MATERIAL AND METHODS: Isolation and identification of E. coli strains from stool specimens are carried out according to standard techniques. Antibiotic susceptibility testing was performed using disc-diffusion method. Plasmid profiling and conjugation experiments were done to analyze the antibiotic resistance transfer from one bacterium cell to another through plasmid. RESULTS: Out of 170 pediatric diarrheal samples, 105 (61.76%) E. coli strains were isolated. About 90% of E. coli strains were resistant to most of the antimicrobial agents tested. All the isolates were resistant to ampicillin, imipenem and cotrimoxazole and were sensitive to amikacin. The resistance to antibiotics shows 29 different antibiotic resistance patterns. About 67 (64%) strains of E. coli isolates harbored plasmids, and 51 (76.1%) of them were able to transfer their plasmids. The plasmid sizes ranged from 1.0 to 25 kb, the most common plasmid of size 4.8 kb being detected in all the plasmid harbored E. coli strains. The results of transconjugation show that all the transconjugant colonies were carrying 4.8-kb plasmid and were resistant to ampicillin, imipenem and cotrimoxazole. CONCLUSION: There is an increase in the prevalence of drug resistance among E. coli isolates, and conjugal transfer of plasmids has greatly contributed to the rapid spread of antibiotic resistance among E. coli isolates. PMID- 20300401 TI - Anamnestic immune response to dengue and decreased severity of yellow Fever. AB - A protective immunity against yellow fever, from cross-reactive dengue antibodies, has been hypothesized as an explanation for the absence of yellow fever in Southern Asia where dengue immunity is almost universal. This study evaluates the association between protective immunity from cross-reactive dengue antibodies with yellow fever infection and severity of the disease. The study population consisted of military personnel of a jungle garrison and its detachments located in the Ecuadorian Amazonian rainforest. The cross-sectional study employed interviews as well as seroepidemiological methods. Humoral immune response to yellow fever, Mayaro, Venezuelan equine encephalitis, Oropouche, and dengue 2 infections was assessed by evaluating IgM and IgG specific antibodies. Log-linear regression analysis was used to evaluate age and presence of antibodies, against dengue type 2 virus, as predictors of yellow fever infection or severe disease. During the seroepidemiological survey, presence of dengue antibodies among yellow fever cases were observed in 77.3% cases from the coastal region, where dengue is endemic, 14.3% cases from the Amazon and 16.7 % cases from the Andean region. Dengue cross-reactive antibodies were not significantly associated with yellow fever infection but significantly associated with severity of the disease. The findings of this study suggest that previous exposure to dengue infection may have induced an anamnestic immune response that did not prevent yellow fever infection but greatly reduced the severity of the disease. PMID- 20300402 TI - Mitigation approaches to combat the flu pandemic. AB - Management of flu pandemic is a perpetual challenge for the medical fraternity since time immemorial. Animal to human transmission has been observed thrice in the last century within an average range of 11-39 years of antigenic recycling. The recent outbreak of influenza A (H1N1, also termed as swine flu), first reported in Mexico on April 26, 2009, occurred in the forty first year since last reported flu pandemic (July 1968). Within less than 50 days, it has assumed pandemic proportions (phase VI) affecting over 76 countries with 163 deaths/35,928 cases (as on 15(th) June 2009). It indicated the re-emergence of genetically reassorted virus having strains endemic to humans, swine and avian (H5N1). The World Health Organisation (WHO) member states have already pulled up their socks and geared up to combat such criticalities. Earlier outbreaks of avian flu (H5N1) in different countries led WHO to develop pandemic preparedness strategies with national/regional plans on pandemic preparedness. Numerous factors related to climatic conditions, socio-economic strata, governance and sharing of information/logistics at all levels have been considered critical indicators in monitoring the dynamics of escalation towards a pandemic situation.The National Disaster Management Authority (NDMA), Government of India, with the active cooperation of UN agencies and other stakeholders/experts has formulated a concept paper on role of nonhealth service providers during pandemics in April 2008 and released national guidelines - management of biological disasters in July 2008. These guidelines enumerate that the success of medical management endeavors like pharmaceutical (anti-viral Oseltamivir and Zanamivir therapies), nonpharmaceutical interventions and vaccination development etc., largely depends on level of resistance offered by mutagenic viral strain and rationale use of pharmaco therapeutic interventions. This article describes the mitigation approach to combat flu pandemic with its effective implementation at national, state and local levels. PMID- 20300404 TI - The Case of the Infection that Wasn't ! AB - Eosinophilic esophagitis is an under-recognized inflammatory disorder of the esophagus. It has been frequently diagnosed in pediatric patients; however, over the last few years, there has been an increase in the number of cases recognized in adults as well. Despite this fact, eosinophilic esophagitis (EE) is often a delayed diagnosis in the primary care setting due to the overlapping symptoms it shares with other esophageal and gastrointestinal disorders such as gastroesophageal reflux disease and gastroenteritis, as well as a lack of awareness among physicians who see adult patients. We performed an exhaustive search of the literature, which revealed over 400 articles on EE; however, most were reported in gastroenterology or autoimmune specialty journals. We report a case of eosinophilic esophagitis in a 39-year-old man who presented with persistent epigastric abdominal pain and who was diagnosed via endoscopy and biopsy. PMID- 20300403 TI - The rise of an opportunistic infection called "Invasive Zygomycosis". AB - Invasive zygomycosis is a devastating fungal infection seen mostly in immune compromised patients. We present a case of a 48-year old diabetic man, with aplastic anemia, who developed severe pulmonary mucormycosis that led to his rapid demise despite early diagnosis and treatment with liposomal amphotericin B. We also conducted an extensive review of the pathogenesis of invasive zygomycosis, its history, predisposing factors, clinical aspects, diagnostic modalities, treatment options, morbidity and mortality. PMID- 20300405 TI - Biliary ascariasis on magnetic resonance cholangiopancreatography. AB - A 17-year-old girl presented with features of biliary obstruction. Magnetic resonance cholangi-pancreatography revealed typical linear signals in common bile duct, which appears like Ascaris lumbricoides. The diagnosis was confirmed by endoscopic removal of the worm. PMID- 20300406 TI - Rhabdomyolysis in a Child Secondary to Staphylococcus aureus Endocarditis. AB - Rhabdomyolysis secondary to bacterial infection has only rarely been investigated, and there are case reports of the same mainly in adults. This article describes the first reported case of rhabdomyolysis in a child secondary to Staphylococcus aureus endocarditis. A 12-year-old child presented with myalgia, pyrexia and dark urine and was found to have infective endocarditis due to S. aureus. PMID- 20300407 TI - Periodontitis, a true infection. PMID- 20300408 TI - Urinary tract abscess in nephrectomized renal transplant recipient. PMID- 20300409 TI - Association of urinary tract infection in women with bacterial vaginosis. PMID- 20300410 TI - State of the Globe: Helicobacter pylori and Hepatitis C Together Hamper Health. PMID- 20300411 TI - Helicobacter pylori and Hepatitis C Virus Coinfection in Egyptian Patients. AB - INTRODUCTION: Chronic hepatitis C virus (HCV) infection is a leading cause of end stage liver disease worldwide. It has been shown that Helicobacter pylori (H. pylori) plays an important role in chronic gastritis, peptic ulcer disease and gastric malignancies, and its eradication has been advocated. The association between H. pylori infection and liver cirrhosis in patients with hepatitis C virus has been documented in different parts of the world; nevertheless, no conclusive data is available in Egypt. MATERIALS AND METHODS: In the present study, the status of H. pylori infection was sought in 90 patients with chronic HCV infection and in 66 HCV-free healthy controls. RESULTS: The study showed that the H. pylori positivity was increased significantly (P = 0.03) in the HCV infected patients when compared to that in healthy controls, where H. pylori infection was found in 50 (55.6%) out of 90 of the HCV-infected patients versus 26 (39.4%) out of 66 of the healthy controls. In HCV-infected patients, the prevalence of H. pylori infection was increased significantly (P = 0.04) from chronic active hepatitis to cirrhosis. H. pylori infection was present in 6/18 (33.3%), 10/21 (47.6%), 16/27 (59.3%), 18/24 (75.0%) patients with chronic active hepatitis, Child-Pugh score A, Child-Pugh score B and Child-Pugh score C, respectively. More importantly, the prevalence of H. pylori infection in HCV infected patients was increased very significantly (P = 0.003) with increasing Meld (model for end-stage liver disease) score. The prevalence of H. pylori was documented in 9/28 (32.1%) patients with Meld score >10 and in 41/62 (66.1%) patients with Meld score >10. CONCLUSION: It may be stated that our results collectively reflect a remarkable increase in H. pylori prevalence with advancing hepatic lesions, and the eradication treatment may prove beneficial in those patients with chronic hepatitis C. PMID- 20300412 TI - Reporting Emerging Resistance of Streptococcus pneumoniae from India. AB - BACKGROUND: There are reports of emergence of resistant strains of S. pneumoniae showing resistance to penicillin from all over the world, and now, resistance to multiple drugs (multidrug-resistant strains) has been added to it. However, scanty reports are available so far from India, depicting such resistance. AIMS: The aim of the present study is to look for the prevalence of penicillin resistant pneumococci and also the multidrug-resistant strains among S. pneumoniae, isolated from respiratory specimens, in the coastal part of South India. SETTINGS AND DESIGN: A cross-sectional study was conducted from June 2008 to December 2008, in our tertiary care center. Fifty pathogenic clinical isolates were collected from patients suffering from lower respiratory tract infections. MATERIALS AND METHODS: Penicillin resistance was screened by 1 mug oxacillin disk on Muller-Hinton blood agar followed by Minimum Inhibitory Concentration (MIC) detection by the agar dilution method according to the Clinical Laboratory Standards Institute (CLSI) guidelines. Antibiotic susceptibility for other antibiotics was carried out by the Kirby Bauer disk diffusion method followed by an E-test with HiComb test strips from Hi-media. RESULTS: Out of 50 isolates, 4% (95% Confidence Interval - 1.4, 9.4) showed total resistance to penicillin, whereas, 10% (95% CI; 1.6, 18.3) showed intermediate resistance. These penicillin resistant pneumococci (4%) were also found to be multidrug-resistant (MDR) strains. Maximum resistance was observed for cotrimoxazole and tetracycline (24% each with 95% CI; 12.2, 35.8) followed by erythromycin and ciprofloxacin (14% each with 95%CI; 4.4, 23.6). CONCLUSIONS: Increasing emergence of the resistant strains of S. pneumoniae in the community set up requires continuous monitoring and a restricted use of antibiotics to keep a check on its resistance pattern, for an effective treatment plan. PMID- 20300413 TI - Looking at Complicating Non-Biological Issues in Women with HIV. AB - INTRODUCTION: The increasing number of women acquiring Human Immunodeficiency Virus (HIV) has resulted in a 'feminization' of the epidemic. In this article we are reviewing whether females are disadvantaged in the epidemic, due to factors independent of the biological differences in sexes. MATERIALS AND METHODS: We searched MEDLINE and EMBASE for articles with key words 'Women', 'Gender,' and 'HIV' in any field. The search was restricted to articles published in English within the last 10 years (1999-2009). Data were coded independently by two reviewers from 94 selected sources. The coded data were categorized under five commonly encountered concepts; violence, poverty, gender norms, prevention /treatment-related issues, and Highly Active Anti-Retroviral Treatment (HAART). RESULTS: The link between inter-partner violence (IPV) and HIV risk for women is observed by many authors. In assessing the link between poverty and HIV, indicators such as food insufficiency and income inequality may be better indicators compared to wealth itself. Although women are disadvantaged with male dominated gender norms, evidence suggests that the traditional norms are changing in many societies. A positive association between living in urban communities, education, and better HIV knowledge has been observed in females, although it is not always synonymous with reduced risk behavior. CONCLUSIONS: Women are still disadvantaged in many HIV-related issues such as poverty, violence, and gender norms. At least in Africa, there is evidence of a positive change in spheres of education and gender norms. However, the situation in Asia is largely unexplored. PMID- 20300415 TI - A novel tool for classification of epidemiological data of vector-borne diseases. AB - In this article we present a novel tool that renders efficient classification of epidemiological data of vector-borne diseases. This algorithm has been applied on the data of the Filariasis disease and the results are compared with the well known k-nearest neighbor algorithm. PMID- 20300414 TI - Hepatitis B vaccination status and needlestick injuries among healthcare workers in syria. AB - BACKGROUND: Although a majority of countries in the Middle East show intermediate or high endemicity of hepatitis B virus (HBV) infection, which clearly poses a serious public health problem in the region, the situation in the Republic of Syria remains unclear. The aim of this study is to determine the hepatitis B vaccination status, to assess the number of vaccinations administered, and to estimate the annual incidence of needlestick injuries (NSIs) among healthcare workers (HCWs) in Aleppo University hospitals. MATERIALS AND METHODS: A cross sectional design with a survey questionnaire was used for exploring details of NSIs during 2008, hepatitis B vaccination status, and HBV infection among a random stratified sample of HCWs in three tertiary hospitals in Aleppo (n = 321). RESULTS: Two hundred and forty-six (76.6%) HCWs had sustained at least one NSI during 2008. Nine (2.8%) had HBV chronic infection and 75 HCWs (23.4%) were never vaccinated. Anesthesiology technicians had the greatest exposure risk when compared to office workers [OR = 16,95% CI (2.55-100), P < 0.01], doctors [OR = 10,95% CI (2.1 47.57), P < 0.01], and nurses [OR = 6.75,95% CI (1.56-29.03), P = 0.01]. HCWs under 25 and between the age of 25 and 35 years were at increased risk for NSI when compared to HCWs older than 45 years [OR = 3.12,95% CI (1.19 8.19), P = 0.02] and [OR = 3.05,95% CI (1.42-6.57), P < 0.01], respectively. CONCLUSION: HCWs at Aleppo University hospitals are frequently exposed to blood borne infections. Precautions and protection from NSIs are important in preventing infection of HCWs. Education about the transmission of blood-borne infections, vaccination, and post-exposure prophylaxis must be implemented and strictly monitored. PMID- 20300416 TI - Rural Epidemiology of HIV Positive Tribal Patients from Chhattisgarh in India. AB - OBJECTIVE: The primary objective was to study the epidemiology of Human Immunodeficiency Virus (HIV) positive tribal patients, and the secondary objective was to study the associated comorbidities in a tertiary care hospital in the tribal (Bastar) region of Chhattisgarh, India, between December 2006 and November 2008, and their relation to CD4 counts. MATERIALS AND METHODS: In this study 90 tribal HIV positive subjects were enrolled. Information on demographics, that is, weight, height, age, educational status, sex, clinical finding, and laboratory parameters (CD4 counts) were noted. RESULTS: Among 90 HIV patients, 54 (60%) were males and 36 (40%) were females. Among these, most patients, 37 (41.1%), were in the age group of 30 to 39 years. Among these patients, 79.56% belonged to the lower socioeconomic status, whereas, only 1.45% were from a high socioeconomic status. The largest group was made up of drivers (32.2%), with the second largest group being housewives (27.7%) and laborers (17.7%), respectively. A majority of the patients had a low education, 35.5% were educated only up to the fifth standard and 31.8% up to high school, while 18.8% were illiterate. The predominant mode of transmission was heterosexual contact (78.8%), only one patient (1.1%) was infected through transfusion of infected blood, five (5.5%) patients acquired infection via vertical (mother to child) transmission, and in 13 patients the transmission history was not clear. CONCLUSION: There was a high frequency of behavioral risk factors, together with unawareness, and very little health infrastructure, thus creating an impending risk for the rapid spread of HIV/AIDS (acquired immunodeficiency syndrome). PMID- 20300417 TI - Recommendations for control of East african sleeping sickness in Uganda. AB - East African sleeping sickness, caused by Trypanosoma brucei rhodesiense, is prominent in Uganda and poses a serious public health challenge in the region. This publication attempts to provide key components for designing a strategy for a nationwide initiative to provide insecticide-treatment of the animal reservoir to control T. b. rhodesiense. The contents of this article will focus on insecticide-based vector control strategies, monitoring and evaluation framework, and knowledge gaps required for future initiatives. PMID- 20300419 TI - Oral sex, oral health and orogenital infections. AB - Oral sex is commonly practiced by sexually active male-female and same-gender couples of various ages, including adolescents. The various type of oral sex practices are fellatio, cunnilingus and analingus. Oral sex is infrequently examined in research on adolescents; oral sex can transmit oral, respiratory, and genital pathogens. Oral health has a direct impact on the transmission of infection; a cut in your mouth, bleeding gums, lip sores or broken skin increases chances of infection. Although oral sex is considered a low risk activity, it is important to use protection and safer sex precautions. There are various methods of preventing infection during oral sex such as physical barriers, health and medical issues, ethical issues and oral hygiene and dental issues. The lesions or unhealthy periodontal status of oral cavity accelerates the phenomenon of transmission of infections into the circulation. Thus consequences of unhealthy or painful oral cavity are significant and oral health should be given paramount importance for the practice of oral sex. PMID- 20300418 TI - Revisiting Methicillin-Resistant Staphylococcus aureus Infections. AB - Within less than 50 years, methicillin-resistant Staphylococcus aureus (MRSA) made a tremendous impact worldwide. It is not limited to medical facilities and healthcare institutions anymore. Indeed since two decades, cases of MRSA infections arising from the community among apparently healthy individuals are increasing. In this paper, I will present a case of community-associated MRSA sepsis followed by a comprehensive review about the history, pathogenesis, epidemiology, clinical presentations, diagnostic modalities, therapeutic options, contributing factors, growing cost and other pertinent elements of this newly evolving epidemic of MRSA infections. PMID- 20300420 TI - Cryptococcal osteomyelitis in the ribs. AB - Isolated cryptococcal osteomyelitis, in an immunocompetent, is rare and only a few cases have been reported in literature. We present the case of a 30-year-old man presented with pain on the left side of chest with fever and gradually increasing swelling in left lateral lower aspect of chest. Investigation revealed a lytic lesion in the anterior end of left 6(th) rib with normal CD4 count. He was tested negative for HIV antigen. Excision of the sixth rib, morphologically revealed cryptococcal osteomyelitis and the patient was given anti-fungal treatment for six months. PMID- 20300421 TI - Trigeminal Neuralgia in an HIV Patient. AB - Trigeminal neuralgia is a painful condition affecting face. Its commonest cause is the tortuous vessels in prepontine cistern. There are other causes also, like brainstem lesions and mass lesions, as well as inflammatory causes. We present a case of an HIV patient with marked involvement of trigeminal nerves, which is a unique finding in immunocompromised patients. PMID- 20300422 TI - Enterococcal Cerebellopontine Angle Abscess in a 12-year-old Female. AB - Despite advances in imaging and antibiotic treatment, brain abscess is still encountered occasionally. Various aerobic and anaerobic bacteria have been reported as causative agents of brain abscess but only a few cases of enterococcal brain abscesses have been reported. Here we report a case of brain abscess in a 12-year-old female patient, who presented with a history of fever, chills, headache, convulsions since seven days and history of altered sensorium and aphasia since the last two days. The patient had chronic suppurative otitis media of both ears following trauma and presented with ear discharge. The diagnosis of brain abscess was done by computerized tomography scan and the pus was aspirated by left suboccipital burr hole operation. Enterococcus species was cultured from the aspirated pus sample. The patient responded to surgical drainage and antibiotic treatment. PMID- 20300423 TI - Pharyngeal histoplasmosis presenting as a tumor mass in an immunocompetent host. PMID- 20300424 TI - Tubercular infection presenting as sinus over ankle joint after knee replacement surgery. PMID- 20300425 TI - Acute myocardial infarction in a hospital cohort of malaria. PMID- 20300426 TI - Fulminant nonocclusive mesenteric ischemia just after hip arthroplasty. AB - Nonocclusive mesenteric ischemia (NOMI) is not a rare clinical entity in intensive medicine, and it can be a consequence of several clinical or surgical situations. This pathology results from reduced intestinal microvascular blood supply associated with an acute inflammatory process, culminating with bowel necrosis. This is a case on a female patient who developed immediate postsurgical NOMI following hip arthroplasty and died. Since diagnosis of this potentially fatal condition remains a dilemma, NOMI should always be considered an eventual postoperative complication in high-risk surgical patients such as elderly individuals with previous history of nicotine abuse, congestive heart failure, and essential hypertension. The present paper highlights the importance of early diagnosis and prompt adequate treatment of NOMI in subjects with diminished cardiac output and severe abdominal pain. PMID- 20300428 TI - Intraosseous hemangioma of the inferior turbinate. AB - The nasal cavity harbors an enormous variety of neoplasms, including epithelial and mesenchymal tumors. Hemangioma is an infrequent mesenchymal tumor of the nasal cavity, mostly arising in the mucosa and rarely in the bones. We describe the case of a 73-year-old woman who was referred to our hospital with a tumor in her left nasal cavity. The tumor originated from the left inferior turbinate. Histological examination subsequent to complete excision revealed that the tumor was an intraosseous cavernous hemangioma. To our knowledge, this is the second case of intraosseous hemangioma of the inferior turbinate reported in the English literature. PMID- 20300427 TI - ICAM-1 clustering on endothelial cells recruits VCAM-1. AB - In the initial stages of transendothelial migration, leukocytes use the endothelial integrin ligands ICAM-1 and VCAM-1 for strong adhesion. Upon adhesion of the leukocyte to endothelial ICAM-1, ICAM-1 is clustered and recruited to the adhered leukocyte, promoting strong adhesion. In this study, we provide evidence for the colocalization of VCAM-1 at sites of ICAM-1 clustering. Anti-ICAM-1 antibody-coated beads were used to selectively cluster and recruit ICAM-1 on primary human endothelial cells. In time, co-localization of ICAM-1 and VCAM-1 around the adherent beads was observed. Biochemical pull-down assays showed that ICAM-1 clustering induced its association to VCAM-1, suggesting a physical link between these two adhesion molecules. The association was partly dependent on lipid rafts as well as on F-actin and promoted adhesion. These data show that VCAM-1 can be recruited, in an integrin-independent fashion, to clustered ICAM-1 which may serve to promote ICAM-1-mediated leukocyte adhesion. PMID- 20300430 TI - The Effectiveness of an After-school Program Targeting Urban African American Youth. AB - The present study reports on the effectiveness at one-year follow-up of an after school prevention program targeting 6(th) grade African American youth residing in high-risk urban areas. The program, conducted on-site over the school-year period, involved a group mentoring approach emphasizing remedial education and an appreciation of African American cultural heritage in promoting school bonding, social skills development, and greater academic achievement. Behavioral and adjustment outcome data were obtained from two participating middle-school sites (intervention and comparison, involving 237 and 241 students, respectively) serving essentially equivalent urban communities. Results of the study revealed significant effects for academic achievement and behavior in terms of grade point average and teacher ratings that favored students at the intervention site. At this site, greater participation of parents in the intervention program was found to be positively related to improvement of the children in grade point average. No differential site-related changes in negative behavior were observed. PMID- 20300429 TI - Cytokines and their STATs in cutaneous and visceral leishmaniasis. AB - Cytokines play a critical role in shaping the host immune response to Leishmania infection and directing the development of protective and non-protective immunities during infection. Cytokines exert their biological activities through the activation and translocation of transcription factors into the nucleus whether they drive the expression of specific cytokine-responsive genes. Signal transducer and activator of transcription (STATs) are transcription factors which play a critical role in mediating signaling downstream of cytokine receptors and are important for shaping the host immune response during Leishmania infection. Here we discuss the signature cytokines and their associated STATs involved in the host immune response during cutaneous and visceral leishmaniasis. PMID- 20300431 TI - Who wins and who loses? Public transfer accounts for US generations born 1850 to 2090. AB - Public transfer programs in industrial nations are thought to benefit the elderly through pension and health care programs at the expense of the young and future generations. However, this intergenerational picture changes if public education is also considered as a transfer program. We calculate the net present value (NPV) of benefits received minus taxes paid for US generations born 1850 to 2090. Surprisingly, all generations 1950 to 2050 are net gainers, while many current elderly are losers. Windfall gains from starting Social Security and Medicare partially offset windfall losses from starting public education, roughly consistent with the Becker-Murphy theory. PMID- 20300432 TI - An unusual clinical presentation of merkel cell carcinoma: a case report. AB - Introduction. Merkel cell carcinoma is a rare, aggressive neuroendocrine cell carcinoma arising in the sun-exposed skin of elderly patients. Most of these tumors are located in the dermis. An unusual clinical presentation of such a tumor in the subcutis, if not biopsied, may be easily mistaken as a benign lesion. Case Presentation. An 83-year-old white woman presented with a several month history of a painless 7 mm subcutaneous mass that was initially thought to be a lipoma. A conservative follow-up was planned. At the insistence of the patient, an excisional biopsy of the mass was performed revealing a subcutaneous Merkel cell carcinoma. The tumor cells stained positively for CK 20, chromogranin, and synaptophysin. No other primary or metastatic tumors found after a thorough work-up. The patient was treated with local irradiation. She remains disease free at her six-month follow-up visit. Conclusion. When a new growth is encountered in the sun-exposed skin of elderly patients, a biopsy is warranted even if the lesion clinically appears benign. PMID- 20300433 TI - Endonuclease IV is the main base excision repair enzyme involved in DNA damage induced by UVA radiation and stannous chloride. AB - Stannous chloride (SnCl(2)) and UVA induce DNA lesions through ROS. The aim of this work was to study the toxicity induced by UVA preillumination, followed by SnCl(2) treatment. E. coli BER mutants were used to identify genes which could play a role in DNA lesion repair generated by these agents. The survival assays showed (i) The nfo mutant was the most sensitive to SnCl(2); (ii) lethal synergistic effect was observed after UVA pre-illumination, plus SnCl(2) incubation, the nfo mutant being the most sensitive; (iii) wild type and nfo mutants, transformed with pBW21 plasmid (nfo(+)) had their survival increased following treatments. The alkaline agarose gel electrophoresis assays pointed that (i) UVA induced DNA breaks and fpg mutant was the most sensitive; (ii) SnCl(2)-induced DNA strand breaks were higher than those from UVA and nfo mutant had the slowest repair kinetics; (iii) UVA + SnCl(2) promoted an increase in DNA breaks than SnCl(2) and, again, nfo mutant displayed the slowest repair kinetics. In summary, Nfo protects E. coli cells against damage induced by SnCl(2) and UVA + SnCl(2). PMID- 20300434 TI - Vaccines against human carcinomas: strategies to improve antitumor immune responses. AB - Multiple observations in preclinical and clinical studies support a role for the immune system in controlling tumor growth and progression. Various components of the innate and adaptive immune response are able to mediate tumor cell destruction; however, certain immune cell populations can also induce a protumor environment that favors tumor growth and the development of metastasis. Moreover, tumor cells themselves are equipped with various mechanisms that allow them to evade surveillance by the immune system. The goal of cancer vaccines is to induce a tumor-specific immune response that ultimately will reduce tumor burden by tipping the balance from a protumor to an antitumor immune environment. This review discusses common mechanisms that govern immune cell activation and tumor immune escape, and some of the current strategies employed in the field of cancer vaccines aimed at enhancing activation of tumor-specific T-cells with concurrent reduction of immunosuppression. PMID- 20300435 TI - Extracorporeal immunoglobulin elimination for the treatment of severe myasthenia gravis. AB - Myasthenia gravis (MG) is a neuromuscular disorder leading to fluctuating muscle weakness and fatigue. Rarely, long-term stabilization is not possible through the use of thymectomy or any known drug therapy. We present our experience with extracorporeal immunoglobulin (Ig) elimination by immunoadsorption (adsorbers with human Ig antibodies). Acetylcholine receptor antibodies (AChRAs) were measured during long-term monitoring (4.7 +/- 2.9 years; range 1.1-8.0). A total of 474 samples (232 pairs) were analyzed, and a drop in AChRA levels was observed (P = .025). The clinical status of patients improved and stabilized. Roughly 6.8% of patients experienced clinically irrelevant side effects. The method of Ig elimination by extracorporeal immunoadsorption (IA) is a clinical application of the recent biotechnological advances. It offers an effective and safe therapy for severe MG even when the disease is resistant to standard therapy. PMID- 20300437 TI - Identification of four Entamoeba histolytica organellar DNA polymerases of the family B and cellular localization of the Ehodp1 gene and EhODP1 protein. AB - We report the identification of a family of four active genes (Ehodp1, Ehodp2, Ehodp3, and Ehodp4) encoding putative DNA polymerases in Entamoeba histolytica, the protozoan parasite responsible of human amoebiasis. The four Ehodp genes show similarity to DNA polymerases encoded in fungi and plant mitochondrial plasmids. EhODP polypeptides conserve the 3'-5' exonuclease II and 5'-3' polymerization domains, and they have the I, II, and III conserved boxes that characterize them as DNA polymerases of family B. Furthermore, we found in EhODP polymerases two novel A and B boxes, present also in DNA polymerases encoded in fungi mitochondrial plasmids. By in situ PCR, Ehodp1 gene was located in nuclei and in DNA-containing cytoplasmic structures. Additionally, using polyclonal antibodies against a recombinant rEhODP1-168 polypeptide, and confocal microscopy, EhODP1 was located in cytoplasmic DNA-containing structures. PMID- 20300436 TI - Skeletal muscle insulin resistance in endocrine disease. AB - We summarize the existing literature data concerning the involvement of skeletal muscle (SM) in whole body glucose homeostasis and the contribution of SM insulin resistance (IR) to the metabolic derangements observed in several endocrine disorders, including polycystic ovary syndrome (PCOS), adrenal disorders and thyroid function abnormalities. IR in PCOS is associated with a unique postbinding defect in insulin receptor signaling in general and in SM in particular, due to a complex interaction between genetic and environmental factors. Adrenal hormone excess is also associated with disrupted insulin action in peripheral tissues, such as SM. Furthermore, both hyper- and hypothyroidism are thought to be insulin resistant states, due to insulin receptor and postreceptor defects. Further studies are definitely needed in order to unravel the underlying pathogenetic mechanisms. In summary, the principal mechanisms involved in muscle IR in the endocrine diseases reviewed herein include abnormal phosphorylation of insulin signaling proteins, altered muscle fiber composition, reduced transcapillary insulin delivery, decreased glycogen synthesis, and impaired mitochondrial oxidative metabolism. PMID- 20300438 TI - Enhanced muscle growth by plasmid-mediated delivery of myostatin propeptide. AB - Myostatin is a member of the transforming growth factor beta (TGF-beta) superfamily that functions as a negative regulator of skeletal muscle development and growth. Myostatin blockade therefore offers a strategy for promoting muscle growth in livestock production without resorting to genetic manipulation. In this report, we examined the effect of myostatin inhibition by plasmid-mediated delivery of a mutant myostatin propeptide (MProD76A), a natural inhibitor of myostatin, on the growth performance of mice. A significant increase in skeletal muscle mass was observed after a single intramuscular injection of naked plasmid DNA encoding MProD76A into mice. Enhanced muscle growth occurred because of myofiber hypertrophy, but no cardiac muscle hypertrophy and organomegaly was observed in the mice after myostatin inhibition by plasmid-mediated MProD76A delivery. These results demonstrate a promising approach to enhancing muscle growth that warrants further investigation in domestic animals. PMID- 20300439 TI - Anti-inflammatory effects of Inonotus obliquus in colitis induced by dextran sodium sulfate. AB - A total of 28 male BALB/c mice (average weight 20.7 +/- 1.6 g) were divided into 4 treatment groups and fed a commercial diet (A), a commercial diet + induced colitis by dextran sodium sulfate (DSS) (B), Inonotus obliquus (IO) administration (C), and IO administration + induced colitis by DSS (D). IO treatment (C, D) decreased the expression of tumor necrosis factor (TNF)-alpha and signal transducers and activators of transcription (STAT)1 compared to those of the colitis induced group (B). The expressions of IL-4 and STAT6 were decreased in group D compared to the colitis induced group (B). The serum immunoglobulin (Ig)E level decreased in IO treatment groups (C, D) compared to no IO treatment groups (A and B) although there was no significant difference between the IO treatment groups. Extract from IO itself had a weak cytotoxic effect on murine macrophage cell line (RAW264.7 cells). Extract from IO inhibited lipopolysaccharide- (LPS-) induced, TNF-alpha, STAT1, pSTAT1, STAT6, and pSTAT6 production in RAW264.7 cells. PMID- 20300440 TI - Wealth Accumulation and the Health of Union Army Veterans, 1860-1870. AB - How did the wartime health of Union Army recruits affect their wealth accumulation through 1870? Wounds and exposure to combat had strong negative effects on subsequent savings, as did illnesses while in the service. The impact of poor health was particularly strong for unskilled workers. Health was a powerful determinant of nineteenth-century economic mobility. Infectious diseases' influences on wealth accumulation suggest that the economic gains from the improvement of the disease environment should be enormous. The direct economic costs of the Civil War were probably much greater than previously thought, given the persistent adverse health effects of wartime experiences. PMID- 20300441 TI - SU-8-based immunoisolative microcontainer with nanoslots defined by nanoimprint lithography. AB - Cells can secrete biotherapeutic molecules that can replace or restore host function. The transplantation of such cells is a promising therapeutic modality for the treatment of several diseases including type 1 diabetes mellitus. These cellular grafts are encapsulated in semipermeable and immunoisolative membranes to protect them from the host immune system, while allowing the transport of nutrients and small molecules that are required for cell survival and function. The authors report on SU-8-based biocompatible immunoisolative cuboid microcontainers for cell transplantation. Each microcontainer comprises a 300*300*250 or a 1100*1100*250 MUm(3) SU-8 hollowed cuboid base that houses the cells and an optically transparent SU-8-based nanoporous lid that closes the device. The hollowed cuboid base was formed by conventional optical lithography to have 8 nl (200*200*200 MUm(3)) encapsulation volume for cellular payload. The lid comprises a thick SU-8 slab with an array of cylindrical wells, whose bottom surface is sealed with a thin nanoporous SU-8 membrane. The nanoporous membrane was created from a 100 nm grating (width and spacing) initial silicon mold subjected to a repeated cycle of oxidation and wet etching to achieve a 20 nm wide and 200 nm pitch nano silicon grating. Nanoimprinting and oblique-angle metal deposition, followed by inductively coupled plasma etching were utilized to create 15 nm wide and 350-450 nm deep nanoslots in the thin SU-8 membrane. Isolated mouse islets were encapsulated in the hollowed cuboid base and the nanoporous lid was assembled on top. The penetration of large and small molecules into the microcontainer was observed with fluorescence. PMID- 20300442 TI - Hippocampal amnesia disrupts verbal play and the creative use of language in social interaction. AB - BACKGROUND: While the neural substrates and cognitive components of creativity have received considerable attention in cognitive neuroscience, the creative use of language in social interaction has been less well studied. As part of a broader program of research on language-and-memory-in-use in individuals with hippocampal amnesia, we analyzed verbal play, a creative use of language that is pervasive in everyday communicative interaction. AIMS: To identify instances of creative uses of language in the protocols of social and collaborative interactions, to characterize the qualitative nature, and to determine the frequency of these interactions initiated by participants with hippocampal amnesia vs. comparison participants in order to ascertain whether amnesia impairs this aspect of social communication. METHODS AND PROCEDURES: This study uses quantitative group comparisons and detailed discourse analysis to analyze verbal play in the interactional discourse sessions of 4 participants with hippocampal amnesia and 4 healthy (demographically matched) comparison participants, each interacting with a familiar partner while completing a collaborative referencing task and with a researcher between task trials. RESULTS: All participants used verbal play. However, significantly fewer episodes were initiated in sessions with amnesia participants (312) and by participants with amnesia themselves (187) than in sessions with comparison participants (572) and by comparison participants (395). No significant group differences were observed for interactional forms, resources, or functions. Qualitative differences were also observed in amnesia sessions (e.g., more rotely produced episodes, lack of thematically linked episodes). CONCLUSIONS: These findings suggest that hippocampal amnesia disrupts the creative use of language in social interaction and accord with our previous work pointing to impairments in language-and-memory in-use more broadly. These findings highlight the interdependence of language and memory especially in the interactional aspects of communication. PMID- 20300443 TI - Asymmetric total syntheses of (+)- and (-)-versicolamide B and biosynthetic implications. AB - The Diels-Alder reaction is one of the most well-studied, synthetically useful organic transformations. While a significant number of naturally occurring substances are postulated to arise by biosynthetic Diels-Alder reactions, rigorous confirmation of a mechanistically distinct natural Diels-Alderase enzyme remains elusive. Within this context, several related fungi within the Aspergillus genus produce a number of metabolites of opposite absolute configuration including (+)- or (-)-versicolamide B. These alkaloids are hypothesized to arise via biosynthetic Diels-Alder reactions implying that each Aspergillus species possesses enantiomerically distinct Diels-Alderases. Herein, experimental validation of these biosynthetic proposals via deployment of the IMDA reaction as a key step in the asymmetric total syntheses of (+)- and (-) versicolamide B is described. Laboratory validation of the proposed biosynthetic Diels-Alder construction, coupled with the secondary metabolite profile of the producing fungi, reveals that each Aspergillus species has evolved enantiomerically distinct indole oxidases, as well as enantiomerically distinct Diels-Alderases. PMID- 20300444 TI - A Glimpse into Urban Middle Schools on Probation for "Persistently Dangerous" Status: Identifying Malleable Predictors of Fighting. AB - The No Child Left Behind Act requires state boards of education to identify schools that are unsafe. Schools that are identified by measures such as suspension and expulsion rates are subsequently labeled "persistently dangerous." To our knowledge there is no published research that attempts to characterize fighting behavior among youth who may attend schools designated as "persistently dangerous." Two hundred and thirteen sixth grade African American boys and girls attending two urban middle schools on probation for "persistently dangerous" status were examined to investigate differences in demographic characteristics of gender and age and predictor factors of non-parental adult mentorship, parental acceptance of fighting behavior, and peer fighting. These analyses suggest a relationship between the number of peers who fight, youth who believed their parents endorse fighting, and youth without non parental adult mentorship were more likely to fight. This study also indicates that regardless of school status there are modifiable predictors associated with early adolescent fighting. PMID- 20300445 TI - Nano-imaging with Storm. AB - Multicolour, three-dimensional stochastic optical reconstruction microscopy now makes it possible to image cellular structures with near molecular-scale resolution. PMID- 20300446 TI - Legal Consciousness and Responses to Sexual Harassment. AB - Studies of legal mobilization often focus on people who have perceived some wrong, but rarely consider the process that selects them into the pool of potential "mobilizers." Similarly, studies of victimization or targeting rarely go on to consider what people do about the wrong, or why some targets come forward and others remain silent. We here integrate sociolegal, feminist, and criminological theories in a conceptual model that treats experiencing sexual harassment and mobilizing in response to it as interrelated processes. We then link these two processes by modeling them as jointly determined outcomes and examine their connections using interviews with a subset of our survey respondents. Our results suggest that targets of harassment are selected, in part, because they are least likely to tell others about the experience. Strategies that workers employ to cope with and confront harassment are also discussed. We find that traditional formal/informal dichotomies of mobilization responses may not fully account for the range of ways individuals respond to harassment, and we propose a preliminary typology of responses. PMID- 20300447 TI - Products, Partners & Public Health: Transfer of Biomedical Technologies from the U.S. Government. AB - The United States (U.S.) leads the world in government support for non-military research and development (R&D), especially support for work that directly relates to health and human development. A focal point for such investments to date in biomedical research has been the National Institutes of Health (NIH), receiving $23.3 billion in fiscal year 2002. Whether internal or externally based, the biomedical research performed has led to a large variety of novel basic, and clinical research discoveries - all of which generally require commercial partners in order to develop them into products for hospital, physician or patient use. This article describes the role of the NIH, including ways in which it works with corporate partners or licensees to commercialize its funded research into products in order to help fulfill it mission as a healthcare agency within the U.S. Department of Health and Human Services (DHHS). PMID- 20300448 TI - SEGMENTATION OF 3D DEFORMABLE OBJECTS WITH LEVEL SET BASED PRIOR MODELS. AB - We propose a level set based deformable model for the segmentation of multiple objects from 3D medical images using shape prior constraints. As an extension to the level set distribution model of object shape presented in [1][2][3], this paper evaluates the performance of the level set representation of the object shape by comparing it with the point distribution model(PDM)[4] using the Chi square test. We define a Maximum A Posteriori(MAP) estimation model using level set based prior information to realize the segmentation of the multiple objects. To achieve this, only one level set function is employed as the representation of the multiple objects of interest within the image. We then define the probability distribution over the variations of objects contained in a set of training images. We found the algorithm to be computationally efficent, robust to noise, able to handle multidimensional data, and avoids the need for explicit point correspondences during the training phase. Results and validation from various experiments on 2D/3D medical images are demonstrated. PMID- 20300450 TI - Struct-NB: predicting protein-RNA binding sites using structural features. AB - We analyse sequence and structural features of protein-RNA interfaces using RB 147, a non-redundant dataset of protein-RNA complexes extracted from the PDB. We train classifiers using machine learning algorithms to predict protein-RNA interfaces from sequence and structure-derived features of proteins. Our experiments show that Struct-NB, a Naive Bayes classifier that exploits structural features, outperforms its counterparts that use only sequence features to predict protein-RNA binding residues. PMID- 20300449 TI - Personalizing HER2-targeted therapy in metastatic breast cancer beyond HER2 status: what we have learned from clinical specimens. AB - HER2 is over-expressed in approximately 25% to 30% of human metastatic breast cancers, primarily due to gene amplification. There are currently two HER2 targeted therapies approved for clinical use, the monoclonal HER2 antibody trastuzumab and the EGFR/HER2 dual tyrosine kinase inhibitor lapatinib. Although both agents show clinical benefit in a subset of patients with metastatic breast cancer, many patients with HER2-over-expressing metastatic breast tumors do not respond to these agents. Furthermore, those who do show an initial response generally demonstrate disease progression, on average in less than one year. It has become clear that HER2 expression status alone does not adequately predict response to HER2-targeted therapy. Identification and clinical validation of molecular predictors of response to trastuzumab and lapatinib is critical for further personalizing treatment and improving clinical benefit for patients whose tumors over-express HER2. In this review, we discuss published data describing potential predictors of response or resistance to trastuzumab and lapatinib. While a discussion of the preclinical work is provided, the emphasis is placed on potential predictors that have been studied in clinical specimens such as tumor tissue or serum obtained from patients treated with HER2-targeted therapy. The present analysis and synthesis of the available literature therefore contribute towards an emerging knowledgebase to personalize breast cancer treatment taking into factors including but beyond HER2 expression. PMID- 20300451 TI - High Frequency Measurements of Viscoelastic Properties of Hydrogels for Vocal Fold Regeneration. AB - This report describes a torsional wave experiment used to measure the viscoelastic properties of vocal fold tissues and soft materials over the range of phonation frequencies. A thin cylindrical sample is mounted between two hexagonal plates. The assembly is enclosed in an environmental chamber to maintain the temperature and relative humidity at in vivo conditions. The bottom plate is subjected to small oscillations by means of a galvanometer driven by a frequency generator that steps through a sequence of frequencies. At each frequency, measured rotations of the top and bottom plates are used to determine the ratio of the amplitudes of the rotations of the two plates. Comparisons of the frequency dependence of this ratio with that predicted for torsional waves in a linear viscoelastic material allows the storage modulus and the loss angle, in shear, to be calculated by a best-fit procedure. Experimental results are presented for hydrogels that are being examined as potential materials for vocal fold regeneration. PMID- 20300452 TI - Role of Place of Residence on Drinking and Driving among Students in a Hispanic Serving University. AB - This study describes the role of place of residence on drinking and driving among students in a large Hispanic-serving institution. The National College Health Assessment survey was administered during the fall of 2004. 1130 randomly selected students completed this anonymous questionnaire. Hispanic students were less likely to drive after drinking compared to non-Hispanic white students, but Hispanic students were more likely to live with parents (55%) compared with non Hispanic white students (22%). After adjusting for the place of residence, there were no significant differences in drinking and driving between Hispanics and non Hispanic white students. Therefore, in part, lower levels of driving after drinking among Hispanic students was mediated by current place of residence. However, the impact of living with parents was not significant among heavy alcohol users. PMID- 20300453 TI - Single-Vesicle Fusion Assay Reveals Munc18-1 Binding to the SNARE Core Is Sufficient for Stimulating Membrane Fusion. AB - Munc18, an essential regulatory protein for intracellular membrane fusion mediated by SNAREs, is known for stabilizing the closed conformation of syntaxin through the interaction with the N-terminal Habc domain (amino acids 28-146) of syntaxin. In addition, Munc18 accelerates membrane fusion and its interaction with SNARE core and the N-peptide (amino acids 1-24) of syntaxin is thought to be necessary for this function. Using the recently developed fluorescence resonance energy transfer assay to detect the fusion between two individual vesicles harboring cognate SNARE proteins, we studied the effect of Munc18 on the fusion induced by neuronal SNARE proteins by following the mixing of lipid molecules between the two vesicles. We found that Munc18-1 stimulates neuronal SNARE mediated fusion not only with full-length syntaxin 1A but also with a truncated syntaxin 1A that is missing both the Habc domain and the N-peptide. The electron paramagnetic resonance analysis indicates that the SNARE core/Munc18 interaction is responsible for this stimulatory function and the membrane plays a role for establishing this interaction. PMID- 20300454 TI - Use of alternative tobacco products in multiethnic youth from Jujuy, Argentina. AB - This study examines alternative tobacco use among Latin American youth. A self administered survey in a random sample of 27 schools was administered in 2004 in Jujuy, Argentina (N = 3218). Prevalence of alternative tobacco product use was 24.1%; 15.3% of youth used hand-rolled cigarettes, 7.8% smoked cigars, 2.3% chewed tobacco leaf and 1.6% smoked pipe. Among youth who never smoked manufactured cigarettes, alternative product use was rare (2.9%), except for chewing tobacco (22%). In multivariate logistic regression boys were more likely than girls to smoke pipe (OR = 3.1; 95% CI 1.1-8.7); indigenous language was associated with smoking hand-rolled cigarettes (OR = 1.4; 95% CI-1.1-1.9) and pipe (OR = 2.2; 95% CI 1.5-3.4). Working in tobacco sales was a risk factor for chewing tobacco (OR = 2.9; 95% CI: 1.7-4.9) and smoking hand-rolled cigarettes (OR = 1.4; 95% CI 1.1-1.8). Having friends who smoked was associated with chewing tobacco (OR = 1.8; 95% CI 1.0-3.2) and with smoking cigars (OR = 2.1; 95% CI 1.5 2.9). Current drinking and thrill-seeking orientation were associated with cigars and pipe smoking. Findings highlight the importance of surveillance of alternative tobacco products use and availability among youth and for addressing identified risk factors. PMID- 20300456 TI - N-alkyl-N-(phosphonoethyl) substituted (meth)acrylamides - new adhesive monomers for self-etching self-priming one part dental adhesive. AB - Novel N-alkyl-N-(phosphonoethyl) substituted mono-, bis- and tris(meth)acrylamides 3 were synthesized by two different three-step reactions and characterized by IR, (1)H NMR and (13)C NMR spectroscopy as well as refractive index and viscosity. The phosphonoethyl substituted (meth)acrylamide monomers show improved hydrolytic stability compared to carboxylic esters. The highest stability was found for the phosphonoethyl substituted acrylamide monomers. Acrylamides have a larger polymerization enthalpy ranging from -50 to 70 kJ.mol-1 per double bond compared to methacrylamides which show -8.57 to -25.1 kJ.mol-1 per double bond. Depending on their structure (meth)acrylamides 3 exhibit an adhesion to enamel and dentin up to 19.5 MPa. The monomer 3c shows the highest adhesion values to both substrates, namely 15.3 +/- 3.4 MPa to enamel and 18.5 +/- 2.3 MPa to dentin. PMID- 20300455 TI - Regulation of P-glycoprotein in renal proximal tubule epithelial cells by LPS and TNF-alpha. AB - During endotoxemia, the ATP-dependent drug efflux pump P-glycoprotein (Abcb1/P gp) is upregulated in kidney proximal tubule epithelial cells. The signaling pathway through which lipopolysaccharide (LPS) or tumor necrosis factor-alpha (TNF-alpha) regulates P-gp expression and activity was investigated further in the present study. Exposure of rat kidney proximal tubule cells to TNF-alpha alone or TNF-alpha and LPS increased P-gp gene and protein expression levels and efflux activity, suggesting de novo P-gp synthesis. Upon exposure to TNF-alpha in combination with LPS, P-gp activity in renal proximal tubule cells is increased under influence of nitric oxide (NO) produced by inducible NO synthase. Upon exposure to TNF-alpha alone, P-gp upregulation seems to involve TLR4 activation and nuclear factor kappaB (NF-kappaB) translocation, a pathway that is likely independent of NO. These findings indicate that at least two pathways regulate P gp expression in the kidney during endotoxemia. PMID- 20300457 TI - Ring-alkyl connecting group effect on mesogenic properties of p-carborane derivatives and their hydrocarbon analogues. AB - The effect of the phenyl-alkyl connecting group on mesogenic properties of several series of isostructural compounds containing p-carborane (A and B), bicyclo[2.2.2]octane (C), and benzene (D) was investigated using thermal and optical methods. Results demonstrated that mesophase stability in the series containing A-D follows the order (Alk)CH2CH2- < (Alk)OOC- < (Alk)CH2O- < (Alk)COO . Surprisingly, the connecting groups (Alk)CH2CH2- and (Alk)OOC- destabilize the mesophase significantly stronger for carboranes (A and B) than for carbocyclic derivatives (C and D). Analysis indicates that this effect may have quadrupolar and conformational origin. PMID- 20300458 TI - Low temperature enantiotropic nematic phases from V-shaped, shape-persistent molecules. AB - A series of V-shaped, shape-persistent thiadiazole nematogens, based on an oligo(phenylene ethynylene) scaffold with ester groups connected via alkyloxy spacers, was efficiently prepared by a two-step procedure. Phase engineering results in an optimum of the mesophase range and low melting temperature when the nematogens are desymmetrised with a butoxy and a heptyloxy spacer. The mesophases are enantiotropic and over the whole temperature range nematic. For the optimised mesogen structure, optical investigations by conoscopy monitored a uniaxial nematic phase upon cooling from the isotropic phase to room temperature (DeltaT = 150 degrees C). X-ray studies on magnetic-field-aligned samples of this mesogen family revealed a general pattern, indicating the alignment of two molecular axes along individual directors in the magnetic field. These observations may be rationalised with larger assemblies of V-shaped molecules isotropically distributed around the direction of the magnetic field. PMID- 20300459 TI - [3.3]Dithia-bridged cyclophanes featuring a thienothiophene ring: synthesis, structures and conformational analysis. AB - The synthesis of [3.3]dithia-bridged cyclophanes 7, 9 and 11 incorporating a fused heterocycle, thieno[2,3-b]thiophene is described. The structures are established by 1H NMR analysis and, in the case of 11, also by single crystal X ray crystallography. Conformational analysis by variable temperature NMR suggests that cyclophanes 7, 9 and 11 exhibit conformationally rigid bridges and rings at least up to 130 degrees C. Energy minimization of 11 revealed anti-11 to be the most stable conformation. Although, the computed energy difference between the most stable conformation anti-11 and the next higher energy conformation syn-anti 11 is only 2.98 kJ/mol, it is intriguing that 11 does not exhibit thia-bridge inversion even at elevated temperatures. PMID- 20300460 TI - 1-(4-Alkyloxybenzyl)-3-methyl-1H-imidazol-3-ium organic backbone: a versatile smectogenic moiety. AB - The merger of ionic liquid and liquid crystal fields, obtained by using the imidazolium ring as a common element, has allowed us to tailor a new set of materials which associate specific functionalities. These functionalities are consequences of the original properties of the component, ionic liquids, liquid crystals and their association in a single compound. The study of this interesting association led us to elaborate environment-flexible cationic architectures from which mesomorphic properties emerge. Moreover, we have also explored the influence of different anions on the mesomorphic properties. PMID- 20300461 TI - Influence of spacer chain lengths and polar terminal groups on the mesomorphic properties of tethered 5-phenylpyrimidines. AB - Based on 5-(4-hydroxyphenyl)-2-octylpyrimidine 8, 5-phenylpyrimidine derivatives 3-7, 9 with different spacer chain lengths (C(2) up to C(6)) and different terminal polar groups (Br, Cl, N(3), OH, CN) were synthesized by etherification and nucleophilic substitution. The mesomorphic behaviour of these compounds was investigated by differential scanning calorimetry (DSC), polarizing optical microscopy (POM) and X-ray diffraction (WAXS and SAXS) and revealed smectic A mesophases for bromides, chlorides and azides 3, 4 and 6. For these compounds a maximum phase width was observed for the C(5) spacer regardless of the terminal group, whereas the hydroxy- and cyano-substituted derivatives 5 and 7, respectively, were non mesomorphic and showed only melting transitions. PMID- 20300462 TI - Appetitive and aversive visual learning in freely moving Drosophila. AB - To compare appetitive and aversive visual memories of the fruit fly Drosophila melanogaster, we developed a new paradigm for classical conditioning. Adult flies are trained en masse to differentially associate one of two visual conditioned stimuli (CS) (blue and green light as CS) with an appetitive or aversive chemical substance (unconditioned stimulus or US). In a test phase, flies are given a choice between the paired and the unpaired visual stimuli. Associative memory is measured based on altered visual preference in the test. If a group of flies has, for example, received a sugar reward with green light in the training, they show a significantly higher preference for the green stimulus during the test than another group of flies having received the same reward with blue light. We demonstrate critical parameters for the formation of visual appetitive memory, such as training repetition, order of reinforcement, starvation, and individual conditioning. Furthermore, we show that formic acid can act as an aversive chemical reinforcer, yielding weak, yet significant, aversive memory. These results provide a basis for future investigations into the cellular and molecular mechanisms underlying visual memory and perception in Drosophila. PMID- 20300463 TI - Age-related changes in processing speed: unique contributions of cerebellar and prefrontal cortex. AB - Age-related declines in processing speed are hypothesized to underlie the widespread changes in cognition experienced by older adults. We used a structural covariance approach to identify putative neural networks that underlie age related structural changes associated with processing speed for 42 adults ranging in age from 19 to 79 years. To characterize a potential mechanism by which age related gray matter changes lead to slower processing speed, we examined the extent to which cerebral small vessel disease influenced the association between age-related gray matter changes and processing speed. A frontal pattern of gray matter and white matter variation that was related to cerebral small vessel disease, as well as a cerebellar pattern of gray matter and white matter variation were uniquely related to age-related declines in processing speed. These results demonstrate that at least two distinct factors affect age-related changes in processing speed, which might be slowed by mitigating cerebral small vessel disease and factors affecting declines in cerebellar morphology. PMID- 20300464 TI - Gaze-Direction-Based MEG Averaging During Audiovisual Speech Perception. AB - To take a step towards real-life-like experimental setups, we simultaneously recorded magnetoencephalographic (MEG) signals and subject's gaze direction during audiovisual speech perception. The stimuli were utterances of /apa/ dubbed onto two side-by-side female faces articulating /apa/ (congruent) and /aka/ (incongruent) in synchrony, repeated once every 3 s. Subjects (N = 10) were free to decide which face they viewed, and responses were averaged to two categories according to the gaze direction. The right-hemisphere 100-ms response to the onset of the second vowel (N100m') was a fifth smaller to incongruent than congruent stimuli. The results demonstrate the feasibility of realistic viewing conditions with gaze-based averaging of MEG signals. PMID- 20300466 TI - Similarity Grouping and Repetition Blindness are Both Influenced by Attention. AB - Previous studies have reported seemingly conflicting results regarding how the amount of stimulus similarity between two simultaneously presented target stimuli impacts perceptual performance. There are many reports of 'repetition blindness', where individuals do worse when shown two similar stimuli relative to two different stimuli. On the other hand, there are reports of 'similarity grouping', where participants perform better when identifying two similar objects relative to two different objects. This manuscript posits that repetition blindness and similarity grouping coexist and can be elicited in the same subjects in a single task. This not only explains the previous opposite effects of stimulus similarity on task performance, but also provides a unique opportunity to directly compare these opposite effects of stimulus similarity with respect to susceptibility to a modulating factor. Since previous studies have provided inconclusive results on whether attentional relevance can modulate the effect of stimulus similarity on task performance, the current manuscript aims to compare repetition blindness and similarity grouping with respect to their susceptibility to attentional relevance. The results of the first experiment confirmed that both repetition blindness and similarity grouping can be elicited in the same experiment, suggesting that repetition blindness and similarity grouping coexist. The results of the second experiment suggest that both repetition blindness and similarity grouping can be modulated by attentional relevance. These results support the explanation of repetition blindness as a token individuation failure. Furthermore, these results suggest that supposedly pre-attentional grouping mechanisms might not operate as independently from top-down attentional modulations as traditionally thought. PMID- 20300467 TI - Coordinated scaling of cortical and cerebellar numbers of neurons. AB - While larger brains possess concertedly larger cerebral cortices and cerebella, the relative size of the cerebral cortex increases with brain size, but relative cerebellar size does not. In the absence of data on numbers of neurons in these structures, this discrepancy has been used to dispute the hypothesis that the cerebral cortex and cerebellum function and have evolved in concert and to support a trend towards neocorticalization in evolution. However, the rationale for interpreting changes in absolute and relative size of the cerebral cortex and cerebellum relies on the assumption that they reflect absolute and relative numbers of neurons in these structures across all species - an assumption that our recent studies have shown to be flawed. Here I show for the first time that the numbers of neurons in the cerebral cortex and cerebellum are directly correlated across 19 mammalian species of four different orders, including humans, and increase concertedly in a similar fashion both within and across the orders Eulipotyphla (Insectivora), Rodentia, Scandentia and Primata, such that on average a ratio of 3.6 neurons in the cerebellum to every neuron in the cerebral cortex is maintained across species. This coordinated scaling of cortical and cerebellar numbers of neurons provides direct evidence in favor of concerted function, scaling and evolution of these brain structures, and suggests that the common notion that equates cognitive advancement with neocortical expansion should be revisited to consider in its stead the coordinated scaling of neocortex and cerebellum as a functional ensemble. PMID- 20300468 TI - Noradrenergic modulation of intrinsic and synaptic properties of lumbar motoneurons in the neonatal rat spinal cord. AB - Although it is known that noradrenaline (NA) powerfully controls spinal motor networks, few data are available regarding the noradrenergic (NAergic) modulation of intrinsic and synaptic properties of neurons in motor networks. Our work explores the cellular basis of NAergic modulation in the rat motor spinal cord. We first show that lumbar motoneurons express the three classes of adrenergic receptors at birth. Using patch-clamp recordings in the newborn rat spinal cord preparation, we characterized the effects of NA and of specific agonists of the three classes of adrenoreceptors on motoneuron membrane properties. NA increases the motoneuron excitability partly via the inhibition of a K(IR) like current. Methoxamine (alpha(1)), clonidine (alpha(2)) and isoproterenol (beta) differentially modulate the motoneuron membrane potential but also increase motoneuron excitability, these effects being respectively inhibited by the antagonists prazosin (alpha(1)), yohimbine (alpha(2)) and propranolol (beta). We show that the glutamatergic synaptic drive arising from the T13-L2 network is enhanced in motoneurons by NA, methoxamine and isoproterenol. On the other hand, NA, isoproterenol and clonidine inhibit both the frequency and amplitude of miniature glutamatergic EPSCs while methoxamine increases their frequency. The T13-L2 synaptic drive is thereby differentially modulated from the other glutamatergic synapses converging onto motoneurons and enhanced by presynaptic alpha(1) and beta receptor activation. Our data thus show that the NAergic system exerts a powerful and complex neuromodulation of lumbar motor networks in the neonatal rat spinal cord. PMID- 20300469 TI - Molecular length distribution and the formation of smectic phases. AB - The phase diagrams of two mixtures of chemically similar smectogenic mesogens strongly differing in molecular length were investigated. In these mixtures the nematic phase present in the pure short mesogen disappeared rapidly on the addition of the longer mesogen, while the smectic state was preserved. In the smectic state the smectic A phase was the much more stable phase as the smectic C phase disappeared quite rapidly as well. In these compounds the loss of the smectic C phase is accompanied by a decrease in smectic translational order and very small tilt angles. This leads to a concentration induced smectic C to smectic A transition. Thus smectic A seems to be the most stable phase to accommodate mesogenic molecules of substantially different length. These surprising results are of general interest for the understanding of the structure and dynamics of smectic phases, as the structure of these bidisperse smectics is signified by extensive out-of-layer fluctuations. PMID- 20300465 TI - Premorbid cognitive deficits in young relatives of schizophrenia patients. AB - Neurocognitive deficits in schizophrenia (SZ) are thought to be stable trait markers that predate the illness and manifest in relatives of patients. Adolescence is the age of maximum vulnerability to the onset of SZ and may be an opportune "window" to observe neurocognitive impairments close to but prior to the onset of psychosis. We reviewed the extant studies assessing neurocognitive deficits in young relatives at high risk (HR) for SZ and their relation to brain structural alterations. We also provide some additional data pertaining to the relation of these deficits to psychopathology and brain structural alterations from the Pittsburgh Risk Evaluation Program (PREP). Cognitive deficits are noted in the HR population, which are more severe in first-degree relatives compared to second-degree relatives and primarily involve psychomotor speed, memory, attention, reasoning, and social-cognition. Reduced general intelligence is also noted, although its relationship to these specific domains is underexplored. Premorbid cognitive deficits may be related to brain structural and functional abnormalities, underlining the neurobiological basis of this illness. Cognitive impairments might predict later emergence of psychopathology in at-risk subjects and may be targets of early remediation and preventive strategies. Although evidence for neurocognitive deficits in young relatives abounds, further studies on their structural underpinnings and on their candidate status as endophenotypes are needed. PMID- 20300470 TI - Parasympathetic functions in children with sensory processing disorder. AB - The overall goal of this study was to determine if parasympathetic nervous system (PsNS) activity is a significant biomarker of sensory processing difficulties in children. Several studies have demonstrated that PsNS activity is an important regulator of reactivity in children, and thus, it is of interest to study whether PsNS activity is related to sensory reactivity in children who have a type of condition associated with sensory processing disorders termed sensory modulation dysfunction (SMD). If so, this will have important implications for understanding the mechanisms underlying sensory processing problems of children and for developing intervention strategies to address them. The primary aims of this project were: (1) to evaluate PsNS activity in children with SMD compared to typically developing (TYP) children, and (2) to determine if PsNS activity is a significant predictor of sensory behaviors and adaptive functions among children with SMD. We examine PsNS activity during the Sensory Challenge Protocol; which includes baseline, the administration of eight sequential stimuli in five sensory domains, recovery, and also evaluate response to a prolonged auditory stimulus. As a secondary aim we examined whether subgroups of children with specific physiological and behavioral sensory reactivity profiles can be identified. Results indicate that as a total group the children with severe SMD demonstrated a trend for low baseline PsNS activity, compared to TYP children, suggesting this may be a biomarker for SMD. In addition, children with SMD as a total group demonstrated significantly poorer adaptive behavior in the communication and daily living subdomains and in the overall Adaptive Behavior Composite of the Vineland than TYP children. Using latent class analysis, the subjects were grouped by severity and the severe SMD group had significantly lower PsNS activity at baseline, tones and prolonged auditory. These results provide preliminary evidence that children who demonstrate severe SMD may have physiological activity that is different from children without SMD, and that these physiological and behavioral manifestations of SMD may affect a child's ability to engage in everyday social, communication, and daily living skills. PMID- 20300471 TI - Thematic series on supramolecular chemistry. PMID- 20300472 TI - Solvent-free phase-vanishing reactions with PTFE (Teflon(r)) as a phase screen. AB - In a solvent-free phase-vanishing reaction with PTFE (polytetrafluoroethylene, Teflon(r)) tape as the phase screen, a thermometer adapter is utilized to insert a PTFE-sealed tube into the vapor phase above the substrate. Besides avoiding use of solvents, the experimental design is not dependent upon the densities of the reactants and the procedure generates little or no waste while providing the reaction products in high yield and in high purity. PMID- 20300473 TI - Prediction of reduction potentials from calculated electron affinities for metal salen compounds. AB - The electron affinities (EAs) of a training set of 19 metal-salen compounds were calculated using density functional theory. Concurrently, the experimental reduction potentials for the training set were measured using cyclic voltammetry. The EAs and reduction potentials were found to be linearly correlated by metal. The reduction potentials of a test set of 14 different metal-salens were then measured and compared to the predicted reduction potentials based upon the training set correlation. The method was found to work well, with a mean unsigned error of 99 mV for the entire test set. This method could be used to predict the reduction potentials of a variety of metal-salen compounds, an important class of coordination compounds used in synthetic organic electrochemistry as electrocatalysts. PMID- 20300474 TI - An efficient partial synthesis of 4'-O-methylquercetin via regioselective protection and alkylation of quercetin. AB - An efficient partial 5-step synthesis of 4'-O-methylquercetin from quercetin in 63% yield is reported. This strategy relies on the selective protection of the catechol group with dichlorodiphenylmethane in diphenyl ether as solvent and on the selective protection of the hydroxyl groups at positions 3 and 7 with chloromethyl ether. PMID- 20300475 TI - Whole grain for whom and why? AB - A definition of whole grain is a critical first step in investigating health claims for whole grain and its products. Today, there is no internationally accepted definition of whole grain. Some existing definitions are broad and commodity-based, including grains with similar end uses, while others are more restricted. Scientific knowledge must be the basis for inclusion of certain grains. It is better to start with a restricted list of grains (a precautionary principle) and extend this as more knowledge becomes available. An exact definition of the raw materials (milled, cracked, crushed, rolled, or flaked) and knowledge of the components providing health effects would appear to be crucial issues for the European authorities when approving health claims. It is important that health claims are evidence-based, sustainable, and officially validated. PMID- 20300476 TI - Viscous and gravitational contributions to mixing during vertical brine transport in water-saturated porous media. AB - The transport of fluids miscible with water arises in groundwater contamination and during remediation of the subsurface environment. For concentrated salt solutions, i.e., brines, the increased density and viscosity determine mixing processes between these fluids and ambient groundwater. Under downward flow conditions, gravitational and viscous forces work against each other to determine the interfacial mixing processes. Historically, mixing has been modeled as a dispersive process, as viscous fingering, and as a combination of both using approaches that were both analytical and numerical. A compilation of previously reported experimental data on vertical miscible displacements by fluids with significant density and viscosity contrasts reveals some agreement with a stability analysis presented by Hill (1952). Additional experimental data on one dimensional dispersion during downward displacement of concentrated salt solutions by freshwater and freshwater displacement by brines support the stability analysis and provides an empirical representation for dispersion coefficients as functions of a gravity number and a mobility ratio. PMID- 20300477 TI - Clinical and Microbiological Determinants of Outcome in Staphylococcus aureus Bacteraemia. AB - Staphylococcus aureus bacteraemia (SAB) is commonly complicated by metastatic infection or relapse after treatment. Objectives. The study aim was to determine the role of bacterial, host, and management factors in development of complicated SAB. Methods. A prospectively-conducted observational study gathered data on predisposition, management and outcome of 100 consecutive SAB cases. Antibiotic susceptibilities and genetic lineage of bacterial isolates were determined. Further clinical and microbiological data were gathered on two retrospective series from 1999-2000 (n = 57) and 2004 (n = 116). Results. In the prospective cases, 27% met our definition of complicated disease. Expressed as RR and 95% CI, complicated disease was associated with diabetes (1.58, 1.00-2.48), injecting drug use (5.48, 0.88-33.49), community-onset of symptoms (1.4, 1.02-1.92), and symptom duration >/=48 hours prior to starting effective antibiotic therapy (2.10, 1.22-3.61). Uncomplicated disease was associated with the presence of a central line (0.69, 0.55-0.88) and prompt removal of a primary focus (0.71, 0.57 0.90). Neither methicillin resistance nor genetic lineage was associated with complicated disease, but methicillin resistance was associated with higher mortality. Conclusions. This study demonstrates that clinical rather than microbial factors are the major determinants of SAB outcome and underscores the importance of early treatment. PMID- 20300480 TI - Incubation Environment Affects Immune System Development in a Turtle with Environmental Sex Determination. AB - The developmental environment can have lasting effects on posthatching phenotype in oviparous animals. Innate immune response is one important component of fitness in vertebrates because it provides a generalized defense against infection. In addition, because male vertebrates are at a higher risk of infection than females, males may benefit more from increased innate immunity than females. We determined the effects of incubation temperature on the innate immune response of hatchling map turtles (Graptemys) by incubating eggs at a range of male and female producing-temperatures and assessing plasma complement activity in the resulting hatchlings. We found a significant effect of incubation environment on circulating complement in hatchling Graptemys ouachitensis, with male-producing temperatures yielding the highest innate immune response. Most important, these results demonstrate that immune response is affected by developmental environment in a species with environmental sex determination, potentially resulting in sex differences in the ability to fend off pathogens. PMID- 20300481 TI - Church-Based Social Relationships and Change in Self-Esteem Over Time. AB - This study had two goals. The first goal was to see if church-based social relationships are associated with change in self-esteem. Emotional support from fellow church members and having a close personal relationship with God served as measures of church-based social ties. The second goal was to see whether emotional support from fellow church members is more strongly associated with self-esteem than emotional support from secular social network members. The data came from an ongoing nationwide survey of older adults. The findings revealed that having a close personal relationship with God is associated with a stronger sense of self-esteem at the baseline and follow-up interviews. In contrast, emotional support from fellow church members was not associated with self-esteem at either point in time. However, emotional support from secular social network members was related to self-esteem at the baseline but not the follow-up interview. PMID- 20300479 TI - Inflammatory mediators of hepatic steatosis. AB - Nonalcoholic fatty liver disease (NAFLD) is rapidly becoming a world-wide public health problem. NAFLD represents a spectrum of disease ranging from "simple steatosis", which is considered relatively benign, to nonalcoholic steatohepatitis and to NAFLD-associated cirrhosis and end-stage liver disease. The etiology of NAFLD and its progression is complex and remains incompletely understood. The progression of the disease involves many factors. Apart from the two hits, the accumulation of TG and the development of fibrosis and necroinflammatory processes, exit numerous molecules associated with these two hits. Among them we can highlight the pro-inflammatory molecules and adiponectins. This review focuses on the growing evidence from both experimental and human studies suggesting a central role of cytokines in the pathogenesis of NAFLD. We review the role of cytokines as key regulators of insulin sensitivity and hepatic lipid overloading, liver injury and inflammation, and fibrosis with an emphasis on potential therapeutic implications. PMID- 20300478 TI - PPAR/RXR Regulation of Fatty Acid Metabolism and Fatty Acid omega-Hydroxylase (CYP4) Isozymes: Implications for Prevention of Lipotoxicity in Fatty Liver Disease. AB - Fatty liver disease is a common lipid metabolism disorder influenced by the combination of individual genetic makeup, drug exposure, and life-style choices that are frequently associated with metabolic syndrome, which encompasses obesity, dyslipidemia, hypertension, hypertriglyceridemia, and insulin resistant diabetes. Common to obesity related dyslipidemia is the excessive storage of hepatic fatty acids (steatosis), due to a decrease in mitochondria beta-oxidation with an increase in both peroxisomal beta-oxidation, and microsomal omega oxidation of fatty acids through peroxisome proliferator activated receptors (PPARs). How steatosis increases PPARalpha activated gene expression of fatty acid transport proteins, peroxisomal and mitochondrial fatty acid beta-oxidation and omega-oxidation of fatty acids genes regardless of whether dietary fatty acids are polyunsaturated (PUFA), monounsaturated (MUFA), or saturated (SFA) may be determined by the interplay of PPARs and HNF4alpha with the fatty acid transport proteins L-FABP and ACBP. In hepatic steatosis and steatohepatitis, the omega-oxidation cytochrome P450 CYP4A gene expression is increased even with reduced hepatic levels of PPARalpha. Although numerous studies have suggested the role ethanol-inducible CYP2E1 in contributing to increased oxidative stress, Cyp2e1-null mice still develop steatohepatitis with a dramatic increase in CYP4A gene expression. This strongly implies that CYP4A fatty acid omega-hydroxylase P450s may play an important role in the development of steatohepatitis. In this review and tutorial, we briefly describe how fatty acids are partitioned by fatty acid transport proteins to either anabolic or catabolic pathways regulated by PPARs, and we explore how medium-chain fatty acid (MCFA) CYP4A and long-chain fatty acid (LCFA) CYP4Fomega-hydroxylase genes are regulated in fatty liver. We finally propose a hypothesis that increased CYP4A expression with a decrease in CYP4F genes may promote the progression of steatosis to steatohepatitis. PMID- 20300482 TI - Parents' Union Dissolution and Adolescents' School Performance: Comparing Methodological Approaches. AB - We use data from the National Longitudinal Study of Adolescent Health and the Adolescent Health and Academic Achievement Study to estimate how parents' union dissolution influences changes in adolescents' mathematics course work gains, overall grade point average, and course failure rates during a window of approximately 1 year (N = 2,629). A primary purpose of this study is demonstrating the utility of propensity score matching techniques for studying topics such as ours that pose methodological challenges such as dealing with endogeneity and selection bias. We compare propensity score matching techniques to ordinary least squares (OLS) regression methods to show and discuss comparability of results obtained using these different procedures. Findings suggest that associations between parents' union dissolution and achievement may be causal, regardless of method used. PMID- 20300483 TI - Mexican American Mothers and Fathers' Prenatal Attitudes and Father Prenatal Involvement: Links to Mother-Infant Interaction and Father Engagement. AB - The present study examines the associations between Mexican American mothers' and fathers' pregnancy intentions, fathers' participation in prenatal activities and mother-infant interactions and father engagement with 9 month-old infants in a nationally representative sample of 735 infants and their parents participating in the Early Childhood Longitudinal Study - Birth Cohort. After controlling for a host of variables, multiple regressions revealed that when mothers wanted the pregnancy, fathers engaged in more literacy and caregiving activities than when mothers did not want the pregnancy. When couples disagreed about wanting the pregnancy, fathers engaged in more literacy activities and showed more warmth than when they agreed. Relationship quality significantly moderated the effects of parents' wantedness on mother-infant interactions and fathers' engagement in literacy activities. PMID- 20300484 TI - On the String Averaging Method for Sparse Common Fixed Points Problems. AB - We study the common fixed point problem for the class of directed operators. This class is important because many commonly used nonlinear operators in convex optimization belong to it. We propose a definition of sparseness of a family of operators and investigate a string-averaging algorithmic scheme that favorably handles the common fixed points problem when the family of operators is sparse. The convex feasibility problem is treated as a special case and a new subgradient projections algorithmic scheme is obtained. PMID- 20300485 TI - Semiparametric Inference for ROC Curves with Censoring. AB - Comparison of two samples can sometimes be conducted on the basis of analysis of ROC curves. A variety of methods of point estimation and confidence intervals for ROC curves have been proposed and studied well. We develop smoothed empirical likelihood based confidence intervals for ROC curves when the samples are censored and generated from semiparametric models. The resulting empirical log likelihood function is shown to be asymptotically chi-squared. Simulation studies illustrate that the proposed empirical likelihood confidence interval is advantageous over the normal approximation based confidence interval. A real data set is analyzed using the proposed method. PMID- 20300487 TI - The Doubting Process: A Longitudinal Study of the Precipitants and Consequences of Religious Doubt. AB - Religious doubt arises from a process in which there is a precipitant, the experience of doubt, a coping response, and a health-related outcome. We explore this process by assessing whether social factors precipitate doubt and the coping responses that are invoked to deal with it. Moreover, we evaluate whether these coping responses are, in turn, associated with health. The data reveal that, over time, people who encounter more negative interaction with fellow congregants have more doubts about religion, whereas more spiritual support and greater involvement in prayer groups are associated with less religious doubt. The findings further indicate that people who encounter more negative interaction are more likely to suppress religious doubts, but people who attend Bible study groups are more likely to seek spiritual growth when faced with doubt. Finally, the results suggest that suppressing religious doubt is associated with less favorable health, whereas seeking spiritual growth does not have a significant effect. PMID- 20300488 TI - RanGTPase: A Key Regulator of Nucleocytoplasmic Trafficking. AB - RanGTPase belongs to the Ras superfamily of small GTPases. It possesses a distinctive acidic C-terminal DEDDDL motif and predominantly localizes to the nucleus. RanGTPase is known to regulate nucleocytoplasmic trafficking as well as mitotic spindle and nuclear envelope formation. Ran-directed nucleocytoplasmic trafficking is an energy-dependent directional process that also depends on nuclear import or export signals. Ran-directed nucleocytoplasmic trafficking is also facilitated by several cellular components, including RanGTPase, karyopherins, NTF2 and nucleoporins. GTP-bound Ran is asymmetrically distributed in the nucleus, while GDP-bound Ran is predominantly cytoplasmic. Controlled by RanGEF and RanGAP, RanGTPase cycles between the GDP- and GTP-bound states enabling it to shuttle cargoes in an accurate spatial and temporal manner. RanGTPase plays a role in the nuclear import in such a way that GTP-bound Ran dissociates importin:cargo complex in the nucleus and recycles importin back to cytoplasm. Likewise, RanGTPase plays a role in the nuclear export in such a way that nuclear GTP-bound Ran triggers the aggregation of Ran:exportin:cargo trimeric complex which is then transported to cytoplasm while hydrolysis of RanGTP to RanGDP releases the export cargoes in cytoplasm. RanGTPase has been reported to be essential for cell viability and its over-expression is linked to tumorigenesis. Thus, RanGTPase plays a crucial role in regulating key cellular events and alterations in its expression may lead to cancer development and/or progression. PMID- 20300486 TI - Recent Progress on the Stereoselective Synthesis of Cyclic Quaternary alpha-Amino Acids. AB - The most recent papers describing the stereoselective synthesis of cyclic quaternary alpha-amino acids are collected in this review. The diverse synthetic approaches are classified according to the size of the ring and taking into account the bond that is formed to complete the quaternary skeleton. PMID- 20300489 TI - Patient-Specific Vascular NURBS Modeling for Isogeometric Analysis of Blood Flow. AB - We describe an approach to construct hexahedral solid NURBS (Non-Uniform Rational B-Splines) meshes for patient-specific vascular geometric models from imaging data for use in isogeometric analysis. First, image processing techniques, such as contrast enhancement, filtering, classification, and segmentation, are used to improve the quality of the input imaging data. Then, lumenal surfaces are extracted by isocontouring the preprocessed data, followed by the extraction of vascular skeleton via Voronoi and Delaunay diagrams. Next, the skeleton-based sweeping method is used to construct hexahedral control meshes. Templates are designed for various branching configurations to decompose the geometry into mapped meshable patches. Each patch is then meshed using one-to-one sweeping techniques, and boundary vertices are projected to the lumenal surface. Finally, hexahedral solid NURBS are constructed and used in isogeometric analysis of blood flow. Piecewise linear hexahedral meshes can also be obtained using this approach. Examples of patient-specific arterial models are presented. PMID- 20300491 TI - Unpacking Intuition: A Conjecture. AB - Can intuition be taught? The way in which faces are recognized, the structure of natural classes, and the architecture of intuition may all be instances of the same process. The conjecture that intuition is a species of recognition memory implies that human intuitive decision making can be enormously enhanced by virtual simulation. PMID- 20300492 TI - Bridal Pregnancy and Spouse Pairing Patterns in Japan. AB - In this paper, we examined two aspects of recent increases in marriage preceded by pregnancy (bridal pregnancy) in Japan. Using information on 28,973 respondents to the Japanese National Fertility Surveys, we first demonstrated that increases in bridal pregnancy between 1970 and 2002 were concentrated among women without postsecondary education. We then estimated multinomial logistic regression models to evaluate change over time in the association between bridal pregnancy and patterns of educational pairing. Results indicated that bridal pregnancy is associated with a significantly higher likelihood of nonnormative educational pairing and that this relationship has become more pronounced over time. We concluded by evaluating these results in comparative context and speculating about the implications for subsequent family change in Japan. PMID- 20300493 TI - A Stimulus-Oriented Approach to Memory. AB - Our understanding of short-term recognition memory can be enhanced by careful choice and control of test materials. Theory-driven manipulation of memory test stimuli, including visual textures, human faces, and complex sounds, minimize individual differences and make it possible to predict recognition performance for specific combinations of stimulus items. This stimulus-oriented approach to memory reveals that stimulus similarity plays two different important roles in recognition memory. By exploiting tools used in psychophysics, it is possible to generate mnemometric functions-detailed "snapshots" that capture key features of subjects' memory strength. PMID- 20300494 TI - A Comparison of Some Model Order Reduction Methods for Fast Simulation of Soft Tissue Response using the Point Collocation-based Method of Finite Spheres (PCMFS). AB - In this paper we develop the Point Collocation-based Method of Finite Spheres (PCMFS) to simulate the viscoelastic response of soft biological tissues and evaluate the effectiveness of model order reduction methods such as modal truncation, Hankel optimal model and truncated balanced realization techniques for PCMFS. The PCMFS was developed in [1] as a physics-based technique for real time simulation of surgical procedures. It is a meshfree numerical method in which discretization is performed using a set of nodal points with approximation functions compactly supported on spherical subdomains centered at the nodes. The point collocation method is used as the weighted residual technique where the governing differential equations are directly applied at the nodal points. Since computational speed has a significant role in simulation of surgical procedures, model order reduction methods have been compared for relative gains in efficiency and computational accuracy. Of these methods, truncated balanced realization results in the highest accuracy while modal truncation results in the highest efficiency. PMID- 20300495 TI - Efficient molecular surface rendering by linear-time pseudo-Gaussian approximation to Lee-Richards surfaces (PGALRS). AB - The PGALRS (pseudo-Gaussian approximation to Lee-Richards surfaces) algorithm is discussed. By modeling electron density with unphysical pseudo-Gaussian atoms, the Lee-Richards surface can be approximated by a contour level of that density in time approximately linear in the number of atoms. Having that contour level, the atoms and residues closest to that surface can be identified in average time O[n(2/3)log(n)] using a NearTree-based nearest neighbor search. If a high-quality Lee-Richards surface is required, then, as a final stage, one of the standard Lee Richards algorithms can be used but considering only the previously identified surface residues; the typical cost is thereby reduced to O[n(2/3)log(n)], making the overall average time for all the steps O(n). For very large macromolecules, such a reduction in computational burden may be essential to being able to render a meaningful molecular surface. This approach extends the feasible range of application for existing molecular surface software, such as MSMS, to larger macromolecules, especially to macromolecules with more than 50 000 atoms, and can be used as a starting point for surface-based (as opposed to backbone-based) motif identification, e.g. using ProMol. PMID- 20300496 TI - An expedient and new synthesis of pyrrolo[1,2-b]pyridazine derivatives. AB - The reaction of 2-[2-(4-fluorophenyl)-2-oxo-1-phenylethyl]-4-methyl-3-oxo pentanoic acid phenylamide with tertiary butyl carbazate and subsequent condensation of the resulting carbamate derivative with a chalcone provided a facile new approach to pyrrolo[1,2-b]pyridazine derivatives. PMID- 20300497 TI - An enantiomerically pure siderophore type ligand for the diastereoselective 1 : 1 complexation of lanthanide(III) ions. AB - A facile synthesis of a highly preorganized tripodal enterobactine-type ligand 1a H3 consisting of a chiral C3-symmetric macrocyclic peptide and three tridentate 2 amido-8-hydroxyquinoline coordinating units is presented. Complex formation with various metal ions (Al(3+), Ga(3+), Fe(3+), La(3+) and Eu(3+)) was investigated by spectrophotometric methods. Only in the case of La(3+) and Eu(3+) were well defined 1 : 1 complexes formed. On the basis of CD spectroscopy and DFT calculations the configuration at the metal centre of the La(3+) complex was determined to show Lambda helicity. The coordination compounds [(1a)Ln] presented should be prototypes for further lanthanide(III) complexes with an enterobactine analogue binding situation. PMID- 20300490 TI - Inflammation in adult and neonatal stroke. AB - This chapter will discuss the current knowledge of the contribution of systemic and local inflammation in acute and sub-chronic stages of experimental stroke in both the adult and neonate. It will review the role of specific cell types and interactions among blood cells, endothelium, glia, microglia, the extracellular matrix and neurons - cumulatively called "neurovascular unit" - in stroke induction and evolution. Intracellular inflammatory signaling pathways such as nuclear factor kappa beta and mitogen-activated protein kinases, and mediators produced by inflammatory cells such as cytokines, chemokines, reactive oxygen species and arachidonic acid metabolites, as well as the modifying role of age on these mechanisms, will be reviewed as well as the potential for therapy in stroke and hypoxic-ischemic injury. PMID- 20300498 TI - Versatile supramolecular reactivity of zinc-tetra(4-pyridyl)porphyrin in crystalline solids: Polymeric grids with zinc dichloride and hydrogen-bonded networks with mellitic acid. AB - Crystal engineering studies confirm that the zinc-tetra(4-pyridyl)porphyrin building block reveals versatile supramolecular chemistry. In this work, it was found to be reactive in the assembly of both (a) a 2D polymeric array by a unique combination of self-coordination and coordination through external zinc dichloride linkers and (b) an extended heteromolecular hydrogen-bonded network with mellitic acid sustained by multiple connectivity between the component species. PMID- 20300500 TI - Pd/C-mediated synthesis of alpha-pyrone fused with a five-membered nitrogen heteroaryl ring: a new route to pyrano[4,3-c]pyrazol-4(1H)-ones. AB - Pd/C-mediated alkynylation of 5-iodo-pyrazole-4-carboxylic acid, involving the first regioselective construction of alpha-pyrone ring on a pyrazol moiety via tandem coupling-cyclization process, has been developed to afford pyrano[4,3 c]pyrazol-4(1H)-one in a single pot. PMID- 20300499 TI - Control of stilbene conformation and fluorescence in self-assembled capsules. AB - The extensively studied trans-stilbene molecule is known to give only weak fluorescence in solution and inside loosely-fitting synthetic capsules. However, trans-stilbene has been recently studied in the context of antibody interiors, where binding results in strong blue fluorescence. The present research was undertaken to understand the spatial factors that influence stilbene fluorescence. trans-Stilbene was encapsulated in the snug, self-assembled complex 1.1 and exhibited fluorescence quenching due to the distortion of its ground state geometry. When the complex is elongated by incorporating glycouril spacers, trans-stilbene is allowed to adapt a fully coplanar arrangement and fluorescence returns. PMID- 20300501 TI - Hydroxyapatite supported caesium carbonate as a new recyclable solid base catalyst for the Knoevenagel condensation in water. AB - The Knoevenagel condensation between aromatic aldehydes and malononitrile, ethyl cyanoacetate or malonic acid with hydroxyapatite supported caesium carbonate in water is described. HAP-Cs2CO3 was found to be a highly active, stable and recyclable catalyst under the reaction conditions. PMID- 20300502 TI - A short synthesis of +/--cherylline dimethyl ether. AB - A synthesis of +/--cherylline dimethyl ether is reported. The key steps involved are Michael-type addition, radical azidonation of an aldehyde, Curtius rearrangement, and reduction of an isocyanate intermediate followed by Pictet Spengler cyclization. PMID- 20300503 TI - Can we measure catalyst efficiency in asymmetric chemical reactions? A theoretical approach. AB - Small molecule asymmetric catalysts are often described as being "good" or "bad" but to date there has been no way of comparing catalyst efficiency quantitatively. We define a simple formula, Asymmetric Catalyst Efficiency (ACE), that allows for such a comparison. We propose that a catalyst is more efficient if fewer atoms are utilised to give a product in a required enantiomeric excess. We illustrate this concept by analysing several well-known asymmetric catalytic chemical reactions carried out in academic laboratories, and compare small molecule catalysts with enzymes. We conclude that ACE is a useful descriptor for the comparison of diverse catalytic systems. It is also noteworthy that, despite the relatively short period of investigation into small molecule catalysts, they are competitive with enzymes with regards to this measure of catalytic efficiency. PMID- 20300504 TI - Coaxial electrospinning of liquid crystal-containing poly(vinylpyrrolidone) microfibres. AB - With the relatively new technique of coaxial electrospinning, composite fibres of poly(vinylpyrrolidone) with the liquid crystal 4-cyano-4'-octylbiphenyl in its smectic phase as core material could be produced. The encapsulation leads to remarkable confinement effects on the liquid crystal, inducing changes in its phase sequence. We conducted a series of experiments to determine the effect of varying the relative flow rates of inner and outer fluid as well as of the applied voltage during electrospinning on these composite fibres. From X-ray diffraction patterns of oriented fibres we could also establish the orientation of the liquid crystal molecules to be parallel to the fibre axis, a result unexpected when considering the viscosity anisotropy of the liquid crystal kept in its smectic phase during electrospinning. PMID- 20300505 TI - Enantioselective synthesis of tricyclic amino acid derivatives based on a rigid 4 azatricyclo[5.2.1.0]decane skeleton. AB - An enantioselective route to four tricyclic amino acids and N-tosylamides, composed of a central norbornane framework with a 2-endo,3-endo-annelated pyrrolidine ring and a 5-endo-C1 or -C2 side chain, has been developed. A key intermediate was the chiral, N-Boc-protected ketone (1R,2S,6S,7R)-4 azatricyclo[5.2.1.02,6]decan-8-one, available from inexpensive endo-carbic anhydride in five steps and 47% yield. The rigid scaffold makes these amino acid derivatives promising candidates for beta-turn-inducing building blocks in peptidomimetics and for chiral auxiliaries in asymmetric organocatalysis. PMID- 20300506 TI - Flow through reactors for organic chemistry: directly electrically heated tubular mini reactors as an enabling technology for organic synthesis. AB - Until recently traditional heating in organic chemistry has been done with oil heating baths or using electric heat exchangers. With the advent of microwave equipment, heating by microwaves was rapidly introduced as standard method in organic chemistry laboratories, mainly because of the convenient possibility to operate at high temperature accompanied by accelerated reaction rates. In the present contribution we discuss the method of heating small, continuously operated reactors by passing electric current directly through the reactor wall as an enabling technology in organic chemistry. The benefit of this method is that the heat is generated directly inside the reactor wall. By this means high heating rates comparable to microwave ovens can be reached but at much lower cost for the equipment. A tool for the comparison of microwave heating and traditional heating is provided. As an example kinetic data for the acid catalyzed hydrolysis of methyl formate were measured using this heating concept. The reaction is not only a suitable model but also one of industrial importance since this is the main production process for formic acid. PMID- 20300507 TI - Diastereoselective functionalisation of benzo-annulated bicyclic sultams: Application for the synthesis of cis-2,4-diarylpyrrolidines. AB - The cis-dibromination of unsaturated bicyclic bridgehead sultams 5a and 5b, and experiments designed to understand the cis-stereochemical outcome of these reactions, are described. In the case of 5b, a novel solvent dependent carbocation rearrangement occurs with the formation of 18b. cis-Dibromides 13a and 13b undergo regioselective dehydrobromination, and the participation of the resultant vinyl bromide 24a in lithiation and Pd-coupling chemistry is described. In the case of the latter, hydrogenation of the styryl products afforded a single diastereoisomer. These compounds were then studied under dissolved metal reduction conditions, in which the cleavage of both N-S and C-S bonds takes place to afford cis-2,4-diaryl-substituted pyrrolidines 35-37. PMID- 20300508 TI - Ring strain and total syntheses of modified macrocycles of the isoplagiochin type. AB - Macrocycles of the bisbibenzyl-type are natural products that are found exclusively in bryophytes (liverworts). The molecular framework of the subtype "isoplagiochin" is of substantial structural interest because of the chirality of the entire molecule, which arises from two biaryl axes in combination with two helical two-carbon units in a cyclic arrangement. From a structural as well as a synthetic point of view we report on the total synthesis of compounds which possess more rigid two-carbon biaryl bridges like stilbene (E or Z) or even tolane moieties which were introduced starting with a Sonogashira protocol. The McMurry method proved to be a powerful tool for the cyclization to these considerably ring-strained macrocycles. PMID- 20300509 TI - Three step synthesis of single diastereoisomers of the vicinal trifluoro motif. AB - A three step route to single diastereoisomers of the vicinal trifluoromethyl motif is described. The route starts from either syn- or anti-alpha,beta-epoxy alcohols and takes a direct approach in that each of the three steps introduces a fluorine atom in a regio- and stereo-specific manner. Starting from either the syn- or the anti-alpha,beta-epoxy alcohol, stereospecific reactions generate two separate diastereoisomeric series of this motif. The route is a significant improvement on an earlier six step strategy. PMID- 20300510 TI - Nodular worm infection in wild chimpanzees in Western Uganda: a risk for human health? AB - This study focused on Oeosophagostomum sp., and more especially on O. bifurcum, as a parasite that can be lethal to humans and is widespread among humans and monkeys in endemic regions, but has not yet been documented in apes. Its epidemiology and the role played by non-human primates in its transmission are still poorly understood. O. stephanostomum was the only species diagnosed so far in chimpanzees. Until recently, O. bifurcum was assumed to have a high zoonotic potential, but recent findings tend to demonstrate that O. bifurcum of non-human primates and humans might be genetically distinct. As the closest relative to human beings, and a species living in spatial proximity to humans in the field site studied, Pan troglodytes is thus an interesting host to investigate. Recently, a role for chimpanzees in the emergence of HIV and malaria in humans has been documented. In the framework of our long-term health monitoring of wild chimpanzees from Kibale National Park in Western Uganda, we analysed 311 samples of faeces. Coproscopy revealed that high-ranking males are more infected than other individuals. These chimpanzees are also the more frequent crop-raiders. Results from PCR assays conducted on larvae and dried faeces also revealed that O. stephanostomum as well as O. bifurcum are infecting chimpanzees, both species co-existing in the same individuals. Because contacts between humans and great apes are increasing with ecotourism and forest fragmentation in areas of high population density, this paper emphasizes that the presence of potential zoonotic parasites should be viewed as a major concern for public health. Investigations of the parasite status of people living around the park or working inside as well as sympatric non-human primates should be planned, and further research might reveal this as a promising aspect of efforts to reinforce measures against crop raiding. PMID- 20300511 TI - Modulation of hepatocarcinoma cell morphology and activity by parylene-C coating on PDMS. AB - BACKGROUND: The ability to understand and locally control the morphogenesis of mammalian cells is a fundamental objective of cell and developmental biology as well as tissue engineering research. We present parylene-C (ParC) deposited on polydimethylsiloxane (PDMS) as a new substratum for in vitro advanced cell culture in the case of Human Hepatocarcinoma (HepG2) cells. PRINCIPAL FINDINGS: Our findings establish that the intrinsic properties of ParC-coated PDMS (ParC/PDMS) influence and modulate initial extracellular matrix (ECM; here, type I collagen) surface architecture, as compared to non-coated PDMS substratum. Morphological changes induced by the presence of ParC on PDMS were shown to directly affect liver cell metabolic activity and the expression of transmembrane receptors implicated in cell adhesion and cell-cell interaction. These changes were characterized by atomic force microscopy (AFM), which elucidated differences in HepG2 cell adhesion, spreading, and reorganization into two- or three dimensional structures by neosynthesis of ECM components. Local modulation of cell aggregation was successfully performed using ParC/PDMS micropatterns constructed by simple microfabrication. CONCLUSION/SIGNIFICANCE: We demonstrated for the first time the modulation of HepG2 cells' behavior in relation to the intrinsic physical properties of PDMS and ParC, enabling the local modulation of cell spreading in a 2D or 3D manner by simple microfabrication techniques. This work will provide promising insights into the development of cell-based platforms that have many applications in the field of in vitro liver tissue engineering, pharmacology and therapeutics. PMID- 20300512 TI - NADPH oxidase limits innate immune responses in the lungs in mice. AB - BACKGROUND: Chronic granulomatous disease (CGD), an inherited disorder of the NADPH oxidase in which phagocytes are defective in generating superoxide anion and downstream reactive oxidant intermediates (ROIs), is characterized by recurrent bacterial and fungal infections and by excessive inflammation (e.g., inflammatory bowel disease). The mechanisms by which NADPH oxidase regulates inflammation are not well understood. METHODOLOGY/PRINCIPAL FINDINGS: We found that NADPH oxidase restrains inflammation by modulating redox-sensitive innate immune pathways. When challenged with either intratracheal zymosan or LPS, NADPH oxidase-deficient p47(phox-/-) mice and gp91(phox)-deficient mice developed exaggerated and progressive lung inflammation, augmented NF-kappaB activation, and elevated downstream pro-inflammatory cytokines (TNF-alpha, IL-17, and G-CSF) compared to wildtype mice. Replacement of functional NADPH oxidase in bone marrow derived cells restored the normal lung inflammatory response. Studies in vivo and in isolated macrophages demonstrated that in the absence of functional NADPH oxidase, zymosan failed to activate Nrf2, a key redox-sensitive anti-inflammatory regulator. The triterpenoid, CDDO-Im, activated Nrf2 independently of NADPH oxidase and reduced zymosan-induced lung inflammation in CGD mice. Consistent with these findings, zymosan-treated peripheral blood mononuclear cells from X linked CGD patients showed impaired Nrf2 activity and increased NF-kappaB activation. CONCLUSIONS/SIGNIFICANCE: These studies support a model in which NADPH oxidase-dependent, redox-mediated signaling is critical for termination of lung inflammation and suggest new potential therapeutic targets for CGD. PMID- 20300513 TI - Prospects for the development of odour baits to control the tsetse flies Glossina tachinoides and G. palpalis s.l. AB - Field studies were done of the responses of Glossina palpalis palpalis in Cote d'Ivoire, and G. p. gambiensis and G. tachinoides in Burkina Faso, to odours from humans, cattle and pigs. Responses were measured either by baiting (1.) biconical traps or (2.) electrocuting black targets with natural host odours. The catch of G. tachinoides from traps was significantly enhanced ( approximately 5x) by odour from cattle but not humans. In contrast, catches from electric targets showed inconsistent results. For G. p. gambiensis both human and cattle odour increased (>2x) the trap catch significantly but not the catch from electric targets. For G. p. palpalis, odours from pigs and humans increased (approximately 5x) the numbers of tsetse attracted to the vicinity of the odour source but had little effect on landing or trap-entry. For G. tachinoides a blend of POCA (P = 3-n propylphenol; O = 1-octen-3-ol; C = 4-methylphenol; A = acetone) alone or synthetic cattle odour (acetone, 1-octen-3-ol, 4-methylphenol and 3-n propylphenol with carbon dioxide) consistently caught more tsetse than natural cattle odour. For G. p. gambiensis, POCA consistently increased catches from both traps and targets. For G. p. palpalis, doses of carbon dioxide similar to those produced by a host resulted in similar increases in attraction. Baiting traps with super-normal (approximately 500 mg/h) doses of acetone also consistently produced significant but slight (approximately 1.6x) increases in catches of male flies. The results suggest that odour-baited traps and insecticide-treated targets could assist the AU-Pan African Tsetse and Trypanosomiasis Eradication Campaign (PATTEC) in its current efforts to monitor and control Palpalis group tsetse in West Africa. For all three species, only approximately 50% of the flies attracted to the vicinity of the trap were actually caught by it, suggesting that better traps might be developed by an analysis of the visual responses and identification of any semiochemicals involved in short-range interaction. PMID- 20300514 TI - Wolbachia age-sex-specific density in Aedes albopictus: a host evolutionary response to cytoplasmic incompatibility? AB - BACKGROUND: Wolbachia bacteria have invaded many arthropod species by inducing Cytoplasmic Incompatibility (CI). These symbionts represent fascinating objects of study for evolutionary biologists, but also powerful potential biocontrol agents. Here, we assess the density dynamics of Wolbachia infections in males and females of the mosquito Aedes albopitcus, an important vector of human pathogens, and interpret the results within an evolutionary framework. METHODOLOGY/PRINCIPAL FINDINGS: Wolbachia densities were measured in natural populations and in age controlled mosquitoes using quantitative PCR. We show that the density dynamics of the wAlbA Wolbachia strain infecting Aedes albopictus drastically differ between males and females, with a very rapid decay of infection in males only. CONCLUSIONS/SIGNIFICANCE: Theory predicts that Wolbachia and its hosts should cooperate to improve the transmission of infection to offspring, because only infected eggs are protected from the effects of CI. However, incompatible matings effectively lower the fertility of infected males, so that selection acting on the host genome should tend to reduce the expression of CI in males, for example, by reducing infection density in males before sexual maturation. The rapid decay of one Wolbachia infection in Aedes albopictus males, but not in females, is consistent with this prediction. We suggest that the commonly observed reduction in CI intensity with male age reflects a similar evolutionary process. Our results also highlight the importance of monitoring infection density dynamics in both males and females to assess the efficiency of Wolbachia-based control strategies. PMID- 20300515 TI - High dengue case capture rate in four years of a cohort study in Nicaragua compared to national surveillance data. AB - Dengue is a major public health problem in tropical and subtropical regions; however, under-reporting of cases to national surveillance systems hinders accurate knowledge of disease burden and costs. Laboratory-confirmed dengue cases identified through the Nicaraguan Pediatric Dengue Cohort Study (PDCS) were compared to those reported from other health facilities in Managua to the National Epidemiologic Surveillance (NES) program of the Nicaraguan Ministry of Health. Compared to reporting among similar pediatric populations in Managua, the PDCS identified 14 to 28 (average 21.3) times more dengue cases each year per 100,000 persons than were reported to the NES. Applying these annual expansion factors to national-level data, we estimate that the incidence of confirmed pediatric dengue throughout Nicaragua ranged from 300 to 1000 cases per 100,000 persons. We have estimated a much higher incidence of dengue than reported by the Ministry of Health. A country-specific expansion factor for dengue that allows for a more accurate estimate of incidence may aid governments and other institutions calculating disease burden, costs, resource needs for prevention and treatment, and the economic benefits of drug and vaccine development. PMID- 20300516 TI - Influence of urban landscapes on population dynamics in a short-distance migrant mosquito: evidence for the dengue vector Aedes aegypti. AB - BACKGROUND: Dengue viruses are endemic across most tropical and subtropical regions. Because no proven vaccines are available, dengue prevention is primarily accomplished through controlling the mosquito vector Aedes aegypti. While dispersal distance is generally believed to be approximately 100 m, patterns of dispersion may vary in urban areas due to landscape features acting as barriers or corridors to dispersal. Anthropogenic features ultimately affect the flow of genes affecting vector competence and insecticide resistance. Therefore, a thorough understanding of what parameters impact dispersal is essential for efficient implementation of any mosquito population suppression program. Population replacement and genetic control strategies currently under consideration are also dependent upon a thorough understanding of mosquito dispersal in urban settings. METHODOLOGY AND PRINCIPAL FINDINGS: We examined the effect of a major highway on dispersal patterns over a 2 year period. A. aegypti larvae were collected on the east and west sides of Uriah Butler Highway (UBH) to examine any effect UBH may have on the observed population structure in the Charlieville neighborhood in Trinidad, West Indies. A panel of nine microsatellites, two SNPs and a 710 bp sequence of mtDNA cytochrome oxidase subunit 1 (CO1) were used for the molecular analyses of the samples. Three CO1 haplotypes were identified, one of which was only found on the east side of the road in 2006 and 2007. AMOVA using mtCO1 and nuclear markers revealed significant differentiation between the east- and west-side collections. CONCLUSION AND SIGNIFICANCE: Our results indicate that anthropogenic barriers to A. aegypti dispersal exist in urban environments and should be considered when implementing control programs during dengue outbreaks and population suppression or replacement programs. PMID- 20300517 TI - The suppression of immune system disorders by passive attrition. AB - Exposure to infectious diseases has an unexpected benefit of inhibiting autoimmune diseases and allergies. This is one of many fundamental fitness tradeoffs associated with immune system architecture. The immune system attacks pathogens, but also may (inappropriately) attack the host. Exposure to pathogens can suppress the deleterious response, at the price of illness and the decay of immunity to previous diseases. This "hygiene hypothesis" has been associated with several possible underlying biological mechanisms. This study focuses on physiological constraints that lead to competition for survival between immune system cell types. Competition maintains a relatively constant total number of cells within each niche. The constraint implies that adding cells conferring new immunity requires loss (passive attrition) of some cells conferring previous immunities. We consider passive attrition as a mechanism to prevent the initial proliferation of autoreactive cells, thus preventing autoimmune disease. We see that this protection is a general property of homeostatic regulation and we look specifically at both the IL-15 and IL-7 regulated niches to make quantitative predictions using a mathematical model. This mathematical model yields insight into the dynamics of the "Hygiene Hypothesis," and makes quantitative predictions for experiments testing the ability of passive attrition to suppress immune system disorders. The model also makes a prediction of an anti-correlation between prevalence of immune system disorders and passive attrition rates. PMID- 20300518 TI - Phylogeography and population structure of Glossina fuscipes fuscipes in Uganda: implications for control of tsetse. AB - BACKGROUND: Glossina fuscipes fuscipes, a riverine species of tsetse, is the main vector of both human and animal trypanosomiasis in Uganda. Successful implementation of vector control will require establishing an appropriate geographical scale for these activities. Population genetics can help to resolve this issue by characterizing the extent of linkage among apparently isolated groups of tsetse. METHODOLOGY/PRINCIPAL FINDINGS: We conducted genetic analyses on mitochondrial and microsatellite data accumulated from approximately 1000 individual tsetse captured in Uganda and neighboring regions of Kenya and Sudan. Phylogeographic analyses suggested that the largest scale genetic structure in G. f. fuscipes arose from an historical event that divided two divergent mitochondrial lineages. These lineages are currently partitioned to northern and southern Uganda and co-occur only in a narrow zone of contact extending across central Uganda. Bayesian assignment tests, which provided evidence for admixture between northern and southern flies at the zone of contact and evidence for northerly gene flow across the zone of contact, indicated that this structure may be impermanent. On the other hand, microsatellite structure within the southern lineage indicated that gene flow is currently limited between populations in western and southeastern Uganda. Within regions, the average F(ST) between populations separated by less than 100 km was less than approximately 0.1. Significant tests of isolation by distance suggested that gene flow is ongoing between neighboring populations and that island populations are not uniformly more isolated than mainland populations. CONCLUSIONS/SIGNIFICANCE: Despite the presence of population structure arising from historical colonization events, our results have revealed strong signals of current gene flow within regions that should be accounted for when planning tsetse control in Uganda. Populations in southeastern Uganda appeared to receive little gene flow from populations in western or northern Uganda, supporting the feasibility of area wide control in the Lake Victoria region by the Pan African Tsetse and Trypanosomiasis Eradication Campaign. PMID- 20300519 TI - Genetic variations in HSPA8 gene associated with coronary heart disease risk in a Chinese population. AB - BACKGROUND: There is ample evidence that Hsp70 takes part in the progress of coronary heart disease (CHD). This implies that genetic variants of Hsp70 genes such as HSPA8 (HSC70) gene might contribute to the development of CHD. The present study aimed to investigate whether certain genetic variants of HSPA8 gene are associated with CHD in Han Chinese people. METHODOLOGY/PRINCIPAL FINDINGS: A total of 2006 subjects (1003 CHD cases and 1003 age- and sex- matched healthy controls) were recruited. Genetic variants in the HSPA8 gene were identified by sequencing of the gene in 60 unrelated Chinese. Four tag single nucleotide polymorphisms (tagSNPs) (rs2236659, rs2276077, rs10892958, and rs1461496) were selected and genotyped. The function of the significant SNP was evaluated using luciferase reporter assays in two cell lines. By sequencing the promoter and all exons and introns of the HSPA8 gene, 23 genetic variants were identified. One promoter SNP rs2236659 was associated with susceptibility to CHD. Carriers of the "C" allele of rs2236659 had decreased CHD risk with odds ratio (OR) of 0.78 (95% CI: 0.62, 0.98; P = 0.033) after adjustment for conventional risk factors. Haplotype analyses indicated that haplotype GCGC contributed to a lower CHD risk (OR = 0.78, 95% CI: 0.65, 0.93; P = 0.006) compared with the common haplotype AGGT. In a transfection assay, the C allele of rs2236659 showed a 37-40% increase in luciferase expression of the reporter gene luciferase in endothelial and non endothelial cells compared with the T allele. CONCLUSIONS/SIGNIFICANCE: These findings suggest that genetic variants in HSPA8 gene (especially promoter SNP rs2236659) contribute to the CHD susceptibility by affecting its expression level. PMID- 20300520 TI - Cytoprotective effect of the elongation factor-2 kinase-mediated autophagy in breast cancer cells subjected to growth factor inhibition. AB - BACKGROUND: Autophagy is a highly conserved and regulated cellular process employed by living cells to degrade proteins and organelles as a response to metabolic stress. We have previously reported that eukaryotic elongation factor-2 kinase (eEF-2 kinase, also known as Ca(2+)/calmodulin-dependent protein kinase III) can positively modulate autophagy and negatively regulate protein synthesis. The purpose of the current study was to determine the role of the eEF-2 kinase regulated autophagy in the response of breast cancer cells to inhibitors of growth factor signaling. METHODOLOGY/PRINCIPAL FINDINGS: We found that nutrient depletion or growth factor inhibitors activated autophagy in human breast cancer cells, and the increased activity of autophagy was associated with a decrease in cellular ATP and an increase in activities of AMP kinase and eEF-2 kinase. Silencing of eEF-2 kinase relieved the inhibition of protein synthesis, led to a greater reduction of cellular ATP, and blunted autophagic response. We further showed that suppression of eEF-2 kinase-regulated autophagy impeded cell growth in serum/nutrient-deprived cultures and handicapped cell survival, and enhanced the efficacy of the growth factor inhibitors such as trastuzumab, gefitinib, and lapatinib. CONCLUSION/SIGNIFICANCE: The results of this study provide new evidence that activation of eEF-2 kinase-mediated autophagy plays a protective role for cancer cells under metabolic stress conditions, and that targeting autophagic survival may represent a novel approach to enhancing the effectiveness of growth factor inhibitors. PMID- 20300521 TI - Non-invasive bleaching of the human lens by femtosecond laser photolysis. AB - BACKGROUND: Globally, cataract is the leading cause of blindness and impaired vision. Cataract surgery is an attractive treatment option but it remains unavailable in sufficient quantity for the vast majority of the world population living in areas without access to specialized health care. Reducing blindness from cataract requires solutions that can be applied outside operating theatres. Cataract is a protein conformational disease characterized by accumulation of light absorbing, fluorescent and scattering protein aggregates. The aim of the study was to investigate whether these compounds were susceptible to photobleaching by a non-invasive procedure and whether this would lead to optical rejuvenation of the lens. METHODOLOGY/PRINCIPAL FINDINGS: Nine human donor lenses were treated with an 800 nm infra-red femtosecond pulsed laser in a treatment zone measuring 1x1x0.52 mm. After laser treatment the age-induced yellow discoloration of the lens was markedly reduced and the transmission of light was increased corresponding to an optical rejuvenation of 3 to 7 years. CONCLUSIONS/SIGNIFICANCE: The results demonstrate that the age-induced yellowing of the human lens can be bleached by a non-invasive procedure based on femtosecond laser photolysis. Cataract is a disease associated with old age. At the current technological stage, lens aging is delayed but with a treatment covering the entire lens volume complete optical rejuvenation is expected. Thus, femtosecond photolysis has the potential clinical value of replacing invasive cataract surgery by a non-invasive treatment modality that can be placed in mobile units, thus breaking down many of the barriers impeding access to treatment in remote and poor regions of the world. PMID- 20300522 TI - Exploring eye movements in patients with glaucoma when viewing a driving scene. AB - BACKGROUND: Glaucoma is a progressive eye disease and a leading cause of visual disability. Automated assessment of the visual field determines the different stages in the disease process: it would be desirable to link these measurements taken in the clinic with patient's actual function, or establish if patients compensate for their restricted field of view when performing everyday tasks. Hence, this study investigated eye movements in glaucomatous patients when viewing driving scenes in a hazard perception test (HPT). METHODOLOGY/PRINCIPAL FINDINGS: The HPT is a component of the UK driving licence test consisting of a series of short film clips of various traffic scenes viewed from the driver's perspective each containing hazardous situations that require the camera car to change direction or slow down. Data from nine glaucomatous patients with binocular visual field defects and ten age-matched control subjects were considered (all experienced drivers). Each subject viewed 26 different films with eye movements simultaneously monitored by an eye tracker. Computer software was purpose written to pre-process the data, co-register it to the film clips and to quantify eye movements and point-of-regard (using a dynamic bivariate contour ellipse analysis). On average, and across all HPT films, patients exhibited different eye movement characteristics to controls making, for example, significantly more saccades (P<0.001; 95% confidence interval for mean increase: 9.2 to 22.4%). Whilst the average region of 'point-of-regard' of the patients did not differ significantly from the controls, there were revealing cases where patients failed to see a hazard in relation to their binocular visual field defect. CONCLUSIONS/SIGNIFICANCE: Characteristics of eye movement patterns in patients with bilateral glaucoma can differ significantly from age-matched controls when viewing a traffic scene. Further studies of eye movements made by glaucomatous patients could provide useful information about the definition of the visual field component required for fitness to drive. PMID- 20300523 TI - Human breast cancer cell lines co-express neuronal, epithelial, and melanocytic differentiation markers in vitro and in vivo. AB - Differentiation programs are aberrant in cancer cells allowing them to express differentiation markers in addition to their tissue of origin. In the present study, we demonstrate the multi-lineage differentiation potential of breast cancer cell lines to express multiple neuronal/glial lineage-specific markers as well as mammary epithelial and melanocytic-specific markers. Multilineage expression was detected in luminal (MCF-7 and SKBR3) and basal (MDA-MB-231) types of human breast cancer cell lines. We also observed comparable co-expression of these three cell lineage markers in MDA-MB-435 cells in vitro, in MDA-MB-435 primary tumors derived from parental and single cell clones and in lung metastases in vivo. Furthermore, ectoderm multi-lineage transdifferentiation was also found in human melanoma (Ul-MeL) and glioblastoma cell lines (U87 and D54). These observations indicate that aberrant multi-lineage transdifferentiation or lineage infidelity may be a wide spread phenomenon in cancer. PMID- 20300525 TI - N-octanoyl dopamine, a non-hemodyanic dopamine derivative, for cell protection during hypothermic organ preservation. AB - BACKGROUND: Although donor dopamine treatment reduces the requirement for post transplantation dialysis in renal transplant recipients, implementation of dopamine in donor management is hampered by its hemodynamic side-effects. Therefore novel dopamine derivatives lacking any hemodynamic actions and yet are more efficacious in protecting tissue from cold preservation injury are warranted. We hypothesized that variation of the molecular structure would yield more efficacious compounds avoid of any hemodynamic effects. METHODOLOGY/PRINCIPAL FINDINGS: To this end, we assessed protection against cold preservation injury in HUVEC by the attenuation of lactate dehydrogenase (LDH) release. Modification of dopamine by an alkanoyl group increased cellular uptake and significantly improved efficacy of protection. Further variation revealed that only compounds bearing two hydroxy groups in ortho or para position at the benzene nucleus, i.e. strong reductants, were protective. However, other reducing agents like N-acetyl cysteine and ascorbate, or NADPH oxidase inhibition did not prevent cellular injury following cold storage. Unlike dopamine, a prototypic novel compound caused no hemodynamic side-effects. CONCLUSIONS/SIGNIFICANCE: In conclusion, we demonstrate that protection against cold preservation injury by catecholamines is exclusively governed by strong reducing capacity and sufficient lipophilicity. The novel dopamine derivatives might be of clinical relevance in donor pre-conditioning as they are completely devoid of hemodynamic action, their increased cellular uptake would reduce time of treatment and therefore also may have a potential use for non-heart beating donors. PMID- 20300524 TI - Activation of PPARbeta/delta causes a psoriasis-like skin disease in vivo. AB - BACKGROUND: Psoriasis is one of the most frequent skin diseases world-wide. The disease impacts enormously on affected patients and poses a huge financial burden on health care providers. Several lines of evidence suggest that the nuclear hormone receptor peroxisome proliferator activator (PPAR) beta/delta, known to regulate epithelial differentiation and wound healing, contributes to psoriasis pathogenesis. It is unclear, however, whether activation of PPARbeta/delta is sufficient to trigger psoriasis-like changes in vivo. METHODOLOGY/PRINCIPAL FINDINGS: Using immunohistochemistry, we define the distribution of PPARbeta/delta in the skin lesions of psoriasis. By expression profiling, we confirm that PPARbeta/delta is overexpressed in the vast majority of psoriasis patients. We further establish a transgenic model allowing inducible activation of PPARbeta/delta in murine epidermis mimicking its distribution in psoriasis lesions. Upon activation of PPARbeta/delta, transgenic mice sustain an inflammatory skin disease strikingly similar to psoriasis, featuring hyperproliferation of keratinocytes, dendritic cell accumulation, and endothelial activation. Development of this phenotype requires the activation of the Th17 subset of T cells, shown previously to be central to psoriasis. Moreover, gene dysregulation in the transgenic mice is highly similar to that in psoriasis. Key transcriptional programs activated in psoriasis, including IL1-related signalling and cholesterol biosynthesis, are replicated in the mouse model, suggesting that PPARbeta/delta regulates these transcriptional changes in psoriasis. Finally, we identify phosphorylation of STAT3 as a novel pathway activated by PPARbeta/delta and show that inhibition of STAT3 phosphorylation blocks disease development. CONCLUSIONS: Activation of PPARbeta/delta in the epidermis is sufficient to trigger inflammatory changes, immune activation, and signalling, and gene dysregulation characteristic of psoriasis. PMID- 20300526 TI - A novel analytical framework for dissecting the genetic architecture of behavioral symptoms in neuropsychiatric disorders. AB - BACKGROUND: For diagnosis of neuropsychiatric disorders, a categorical classification system is often utilized as a simple way for conceptualizing an often complex clinical picture. This approach provides an unsatisfactory model of mental illness, since in practice patients do not conform to these prototypical diagnostic categories. Family studies show notable familial co-aggregation between schizophrenia and bipolar illness and between schizoaffective disorders and both bipolar disorder and schizophrenia, revealing that mental illness does not conform to such categorical models and is likely to follow a continuum encompassing a spectrum of behavioral symptoms. RESULTS AND METHODOLOGY: We introduce an analytic framework to dissect the phenotypic heterogeneity present in complex psychiatric disorders based on the conceptual paradigm of a continuum of psychosis. The approach identifies subgroups of behavioral symptoms that are likely to be phenotypically and genetically homogenous. We have evaluated this approach through analysis of simulated data with simulated behavioral traits and predisposing genetic factors. We also apply this approach to a psychiatric dataset of a genome scan for schizophrenia for which extensive behavioral information was collected for each individual patient and their families. With this approach, we identified significant evidence for linkage among depressed individuals with two distinct symptom profiles, that is individuals with sleep disturbance symptoms with linkage on chromosome 2q13 and also a mutually exclusive group of individuals with symptoms of concentration problems with linkage on chromosome 2q35. In addition we identified a subset of individuals with schizophrenia defined by language disturbances with linkage to chromosome 2p25.1 and a group of patients with a phenotype intermediate between those of schizophrenia and schizoaffective disorder with linkage to chromosome 2p21. CONCLUSIONS: The findings presented are novel and demonstrate the efficacy of this approach in detection of genes underlying such complex human disorders as schizophrenia and depression. PMID- 20300527 TI - GSK3 influences social preference and anxiety-related behaviors during social interaction in a mouse model of fragile X syndrome and autism. AB - BACKGROUND: Nearly 1% of children in the United States exhibit autism spectrum disorders, but causes and treatments remain to be identified. Mice with deletion of the fragile X mental retardation 1 (Fmr1) gene are used to model autism because loss of Fmr1 gene function causes Fragile X Syndrome (FXS) and many people with FXS exhibit autistic-like behaviors. Glycogen synthase kinase-3 (GSK3) is hyperactive in brains of Fmr1 knockout mice, and inhibition of GSK3 by lithium administration ameliorates some behavioral impairment in these mice. We extended our studies of this association by testing whether GSK3 contributes to socialization behaviors. This used two mouse models with disrupted regulation of GSK3, Fmr1 knockout mice and GSK3 knockin mice, in which inhibitory serines of the two isoforms of GSK3, GSK3alpha and GSK3beta, are mutated to alanines, leaving GSK3 fully active. METHODOLOGY/PRINCIPAL FINDINGS: To assess sociability, test mice were introduced to a restrained stimulus mouse (S1) for 10 min, followed by introduction of a second restrained stimulus mouse (S2) for 10 min, which assesses social preference. Fmr1 knockout and GSK3 knockin mice displayed no deficit in sociability with the S1 mouse, but unlike wild-type mice neither demonstrated social preference for the novel S2 mouse. Fmr1 knockout mice displayed more anxiety-related behaviors during social interaction (grooming, rearing, and digging) than wild-type mice, which was ameliorated by inhibition of GSK3 with chronic lithium treatment. CONCLUSIONS/SIGNIFICANCE: These results indicate that impaired inhibitory regulation of GSK3 in Fmr1 knockout mice may contribute to some socialization deficits and that lithium treatment can ameliorate certain socialization impairments. As discussed in the present work, these results suggest a role for GSK3 in social behaviors and implicate inhibition of GSK3 as a potential therapeutic. PMID- 20300528 TI - A at single nucleotide polymorphism-358 is required for G at -420 to confer the highest plasma resistin in the general Japanese population. AB - Insulin resistance is a feature of type 2 diabetes. Resistin, secreted from adipocytes, causes insulin resistance in mice. We previously reported that the G/G genotype of single nucleotide polymorphism (SNP) at -420 (rs1862513) in the human resistin gene (RETN) increased susceptibility to type 2 diabetes by enhancing its promoter activity. Plasma resistin was highest in Japanese subjects with G/G genotype, followed by C/G, and C/C. In this study, we cross-sectionally analyzed plasma resistin and SNPs in the RETN region in 2,019 community-dwelling Japanese subjects. Plasma resistin was associated with SNP-638 (rs34861192), SNP 537 (rs34124816), SNP-420, SNP-358 (rs3219175), SNP+299 (rs3745367), and SNP+1263 (rs3745369) (P<10(-13) in all cases). SNP-638, SNP -420, SNP-358, and SNP+157 were in the same linkage disequilibrium (LD) block. SNP-358 and SNP-638 were nearly in complete LD (r(2) = 0.98), and were tightly correlated with SNP-420 (r(2) = 0.50, and 0.51, respectively). The correlation between either SNP-358 (or SNP-638) or SNP-420 and plasma resistin appeared to be strong (risk alleles for high plasma resistin; A at SNP-358, r(2) = 0.5224, P = 4.94x10(-324); G at SNP 420, r(2) = 0.2616, P = 1.71x10(-133)). In haplotypes determined by SNP-420 and SNP-358, the estimated frequencies for C-G, G-A, and G-G were 0.6700, 0.2005, and 0.1284, respectively, and C-A was rare (0.0011), suggesting that subjects with A at -358, generally had G at -420. This G-A haplotype conferred the highest plasma resistin (8.24 ng/ml difference/allele compared to C-G, P<0.0001). In THP-1 cells, the RETN promoter with the G-A haplotype showed the highest activity. Nuclear proteins specifically recognized one base difference at SNP-358, but not at SNP-638. Therefore, A at -358 is required for G at -420 to confer the highest plasma resistin in the general Japanese population. In Caucasians, the association between SNP-420 and plasma resistin is not strong, and A at -358 may not exist, suggesting that SNP-358 could explain this ethnic difference. PMID- 20300529 TI - A monomeric variant of insulin degrading enzyme (IDE) loses its regulatory properties. AB - BACKGROUND: Insulin degrading enzyme (IDE) is a key enzyme in the metabolism of both insulin and amyloid beta peptides. IDE is unique in that it is subject to allosteric activation which is hypothesized to occur through an oligomeric structure. METHODOLOGY/PRINCIPAL FINDINGS: IDE is known to exist as an equilibrium mixture of monomers, dimers, and higher oligomers, with the dimer being the predominant form. Based on the crystal structure of IDE we deleted the putative dimer interface in the C-terminal region, which resulted in a monomeric variant. Monomeric IDE retained enzymatic activity, however instead of the allosteric behavior seen with wild type enzyme it displayed Michaelis-Menten kinetic behavior. With the substrate Abz-GGFLRKHGQ-EDDnp, monomeric IDE retained approximately 25% of the wild type activity. In contrast with the larger peptide substrates beta-endorphin and amyloid beta peptide 1-40, monomeric IDE retained only 1 to 0.25% of wild type activity. Unlike wild type IDE neither bradykinin nor dynorphin B-9 activated the monomeric variant of the enzyme. Similarly, monomeric IDE was not activated by polyphosphates under conditions in which the activity of wild type enzyme was increased more than 50 fold. CONCLUSIONS/SIGNIFICANCE: These findings serve to establish the dimer interface in IDE and demonstrate the requirement for an oligomeric form of the enzyme for its regulatory properties. The data support a mechanism where the binding of activators to oligomeric IDE induces a conformational change that cannot occur in the monomeric variant. Since a conformational change from a closed to a more open structure is likely the rate-determining step in the IDE reaction, the subunit induced conformational change likely shifts the structure of the oligomeric enzyme to a more open conformation. PMID- 20300530 TI - Inefficient complement system clearance of Trypanosoma cruzi metacyclic trypomastigotes enables resistant strains to invade eukaryotic cells. AB - The complement system is the main arm of the vertebrate innate immune system against pathogen infection. For the protozoan Trypanosoma cruzi, the causative agent of Chagas disease, subverting the complement system and invading the host cells is crucial to succeed in infection. However, little attention has focused on whether the complement system can effectively control T. cruzi infection. To address this question, we decided to analyse: 1) which complement pathways are activated by T. cruzi using strains isolated from different hosts, 2) the capacity of these strains to resist the complement-mediated killing at nearly physiological conditions, and 3) whether the complement system could limit or control T. cruzi invasion of eukaryotic cells. The complement activating molecules C1q, C3, mannan-binding lectin and ficolins bound to all strains analysed; however, C3b and C4b deposition assays revealed that T. cruzi activates mainly the lectin and alternative complement pathways in non-immune human serum. Strikingly, we detected that metacyclic trypomastigotes of some T. cruzi strains were highly susceptible to complement-mediated killing in non-immune serum, while other strains were resistant. Furthermore, the rate of parasite invasion in eukaryotic cells was decreased by non-immune serum. Altogether, these results establish that the complement system recognizes T. cruzi metacyclic trypomastigotes, resulting in killing of susceptible strains. The complement system, therefore, acts as a physiological barrier which resistant strains have to evade for successful host infection. PMID- 20300531 TI - Hypoxia inactivates the VHL tumor suppressor through PIASy-mediated SUMO modification. AB - The hypoxic microenvironment contributes to embryonic development and tumor progression through stabilization of the potent transcriptional factor HIFalpha. In normoxia, the tumor suppressor protein VHL acts as an E3 ubiquitin ligase to target HIFalpha for proteolytic destruction. Increasing evidence shows that VHL is a multifunctional adaptor involved in inhibition of HIFalpha-dependent and independent cellular processes. However, the molecular effect of hypoxic stress on VHL functions remains elusive. Here we report that PIASy, a SUMO E3 ligase upregulated in hypoxia, interacts with VHL and induces VHL SUMOylation on lysine residue 171. Moreover, PIASy-mediated SUMO1 modification induces VHL oligomerization and abrogates its inhibitory function on tumor cell growth, migration and clonogenicity. Knockdown of PIASy by small interfering RNA leads to reduction of VHL oligomerization and increases HIF1alpha degradation. These findings reveal a unique molecular strategy for inactivation of VHL under hypoxic stress. PMID- 20300532 TI - Transformation of environmental Bacillus subtilis isolates by transiently inducing genetic competence. AB - Domesticated laboratory strains of Bacillus subtilis readily take up and integrate exogenous DNA. In contrast, "wild" ancestors or Bacillus strains recently isolated from the environment can only be genetically modified by phage transduction, electroporation or protoplast transformation. Such methods are laborious, have a variable yield or cannot efficiently be used to alter chromosomal DNA. A major disadvantage of using laboratory strains is that they have often lost, or do not display ecologically relevant physiologies such as the ability to form biofilms. Here we present a method that allows genetic transformation by natural competence in several environmental isolates of B. subtilis. Competence in these strains was established by expressing the B. subtilis competence transcription factor ComK from an IPTG-inducible promoter construct present on an unstable plasmid. This transiently activates expression of the genes required for DNA uptake and recombination in the host strain. After transformation, the comK encoding plasmid is lost easily because of its intrinsic instability and the transformed strain returns to its wild state. Using this method, we have successfully generated mutants and introduced foreign DNA into a number of environmental isolates and also B. subtilis strain NCIB3610, which is widely used to study biofilm formation. Application of the same method to strains of B. licheniformis was unsuccessful. The efficient and rapid approach described here may facilitate genetic studies in a wider array of environmental B. subtilis strains. PMID- 20300534 TI - In vivo accumulation of Helicobacter pylori products, NOD1, ubiquitinated proteins and proteasome in a novel cytoplasmic structure. AB - Cell internalization and intracellular fate of H. pylori products/virulence factors in vivo by human gastric epithelium, the main target of H. pylori-induced pathologies (i.e., peptic ulcer and cancer), are still largely unknown. Investigating gastric endoscopic biopsies from dyspeptic patients by means of ultrastructural immunocytochemistry, here we show that, in human superficial foveolar epithelium and its metaplastic or dysplastic foci, H. pylori virulence factors accumulated in a discrete cytoplasmic structure characterized by 13-nm thick cylindrical particles of regular punctate-linear substructure resembling the proteasome complex in size and structure. Inside this particle-rich cytoplasmic structure (PaCS) we observed colocalization of VacA, CagA, urease and outer membrane proteins with NOD1 receptor, ubiquitin-activating enzyme E1, polyubiquitinated proteins, proteasome components and potentially oncogenic proteins like SHP2 and ERKs in human gastric epithelium. By means of electron and confocal microscopy, we demonstrate that the in vivo findings were reproduced in vitro by incubating human epithelial cell lines with H. pylori products/virulence factors. PaCSs differed from VacA-induced vacuoles, phagosomes, aggresomes or related bodies. Our data suggest that PaCS is a novel, proteasome-enriched structure arising in ribosome-rich cytoplasm at sites of H. pylori products accumulation. As a site of selective concentration of bacterial virulence factors, the ubiquitin-proteasome system and interactive proteins, PaCS is likely to modulate immune-inflammatory and proliferative responses of the gastric epithelium of potential pathologic relevance. PMID- 20300535 TI - Grip force is part of the semantic representation of manual action verbs. AB - Motor actions and action verbs activate similar cortical brain regions. A functional interference can be taken as evidence that there is a parallel treatment of these two types of information and would argue for the biological grounding of language in action. A novel approach examining the relationship between language and grip force is presented. With eyes closed and arm extended, subjects listened to words relating (verbs) or not relating (nouns) to a manual action while holding a cylinder with an integrated force sensor. There was a change in grip force when subjects heard verbs that related to manual action. Grip force increased from about 100 ms following the verb presentation, peaked at 380 ms and fell abruptly after 400 ms, signalling a possible inhibition of the motor simulation evoked by these words. These observations reveal the intimate relationship that exists between language and grasp and show that it is possible to elucidate online new aspects of sensorimotor interaction. PMID- 20300533 TI - Aptamer antagonists of myelin-derived inhibitors promote axon growth. AB - Myelin of the adult central nervous system (CNS) is one of the major sources of inhibitors of axon regeneration following injury. The three known myelin-derived inhibitors (Nogo, MAG, and OMgp) bind with high affinity to the Nogo-66 receptor (NgR) on axons and limit neurite outgrowth. Here we show that RNA aptamers can be generated that bind with high affinity to NgR, compete with myelin-derived inhibitors for binding to NgR, and promote axon elongation of neurons in vitro even in the presence of these inhibitors. Aptamers may have key advantages over protein antagonists, including low immunogenicity and the possibility of ready modification during chemical synthesis for stability, signaling, or immobilization. This first demonstration that aptamers can directly influence neuronal function suggests that aptamers may prove useful for not only healing spinal cord and other neuronal damage, but may be more generally useful as neuromodulators. PMID- 20300536 TI - Molecular evolution of human H1N1 and H3N2 influenza A virus in Thailand, 2006 2009. AB - BACKGROUND: Annual seasonal influenza outbreaks are associated with high morbidity and mortality. OBJECTIVE: To index and document evolutionary changes among influenza A H1N1 and H3N2 viruses isolated from Thailand during 2006-2009, using complete genome sequences. METHODS: Nasopharyngeal aspirates were collected from patients diagnosed with respiratory illness in Thailand during 2006-2009. All samples were screened for Influenza A virus. A total of 13 H1N1 and 21 H3N2 were confirmed and whole genome sequenced for the evolutionary analysis using standard phylogenetic approaches. RESULTS: Phylogenetic analysis of HA revealed a clear diversification of seasonal from vaccine strain lineages. H3N2 seasonal clusters were closely related to the WHO recommended vaccine strains in each season. Most H1N1 isolates could be differentiated into 3 lineages. The A/Brisbane/59/2007 lineage, a vaccine strain for H1N1 since 2008, is closely related with the H1N1 subtypes circulating in 2009. HA sequences were conserved at the receptor-binding site. Amino acid variations in the antigenic site resulted in a possible N-linked glycosylation motif. Recent H3N2 isolates had higher genetic variations compared to H1N1 isolates. Most substitutions in the NP protein were clustered in the T-cell recognition domains. CONCLUSION: In this study we performed evolutionary genetic analysis of influenza A viruses in Thailand between 2006-2009. Although the current vaccine strain is efficient for controlling the circulating outbreak subtypes, surveillance is necessary to provide unambiguous information on emergent viruses. In summary, the findings of this study contribute the understanding of evolution in influenza A viruses in humans and is useful for routine surveillance and vaccine strain selection. PMID- 20300537 TI - Family structure and well-being at older ages in Japan. AB - The family structure of older Japanese is projected to change dramatically as a result of very low fertility, increasing levels of non-marriage, childlessness, and divorce, and declining intergenerational coresidence. To provide an empirical basis for speculation about the implications of projected increases in single person and couple-only households, we use two sources of data to describe relationships between family structure and the physical and emotional well-being of Japanese men and women age 60 and above. We find that marriage is positively associated with self-rated health and emotional well-being among older men but not women. In contrast to expectations, however, we find only limited evidence that the presence of children contributes to well-being. Taken as a whole, our results suggest that declines in marriage may have negative implications for the well-being of older Japanese men while the implications of declines in fertility and intergenerational coresidence may be less than popularly believed. PMID- 20300538 TI - Emotion regulation in depression: relation to cognitive inhibition. AB - Depression is a disorder of impaired emotion regulation. Consequently, examining individual differences in the habitual use of emotion regulation strategies has considerable potential to inform models of this debilitating disorder. The aim of the current study was to identify cognitive processes that may be associated with the use of emotion regulation strategies and to elucidate their relation to depression. Depression has been found to be associated with difficulties in cognitive control and, more specifically, with difficulties inhibiting the processing of negative material. We used a negative affective priming task to assess the relations among inhibition and individual differences in the habitual use of rumination, reappraisal, and expressive suppression in clinically depressed, formerly depressed, and never-depressed participants. We found that depressed participants exhibited the predicted lack of inhibition when processing negative material. Moreover, within the group of depressed participants, reduced inhibition of negative material was associated with greater rumination. Across the entire sample, reduced inhibition of negative material was related to less use of reappraisal and more use of expressive suppression. Finally, within the formerly depressed group, less use of reappraisal, more use of rumination, and greater expressive suppression were related to higher levels of depressive symptoms. These findings suggest that individual differences in the use of emotion regulation strategies play an important role in depression, and that deficits in cognitive control are related to the use of maladaptive emotion regulation strategies in this disorder. PMID- 20300539 TI - Acculturation and Enculturation Trajectories Among Mexican-American Adolescent Offenders. AB - This study examines changes over time in ethnic affirmation/belonging and ethnic identity achievement, Spanish language use, English language use, Mexican/Mexican American affiliation/identification and Anglo affiliation/identification in a sample of Mexican-American adolescents participating in a longitudinal study of juvenile offenders. The Multigroup Ethnic Identity Measure and the Acculturation Rating Scale for Mexican Americans-II were completed by the Mexican-American adolescents 7 times over a 3-year period. The findings from longitudinal growth modeling analyses and growth mixture modeling analyses indicate that there is heterogeneity in the initial scores and changes over time on these variables that are related to markers for the cultural qualities of the home environment (i.e., generational status and mother's most frequent language use). In contrast to expectations, marginalized or assimilated acculturation trajectories/types were not overrepresented in this sample of adolescent offenders. Implications for our understanding of the nature of acculturation and enculturation processes and the way these processes are studied are discussed. PMID- 20300541 TI - A Short-Term Longitudinal Study of the Relationship between Motivation to Read and Reading Fluency Skill in Second Grade. AB - This short-term longitudinal study investigated the relationships between students' reading self-concept, goals for reading, and reading fluency skill over the course of the second grade year. Second grade children (N=185) were administered the Test of Word Reading Efficiency, the second grade Dynamic Indicators of Basic Early Literacy Skills, and an adapted version of Motivation to Read Profile at the beginning, middle, and end of the school year. Results showed that students' goals for reading were related to reading self-concept, but unrelated to reading fluency. In addition, reading self-concept was significantly related to reading fluency at each time point. Latent-variable path analysis was used to test four potential relationships between students' reading self-concept and reading fluency skill: (a) an independence model; (b) a skill development model; (c) a self-enhancement model; and (d) a reciprocal effects model. Support for a reciprocal model was found between students' reading fluency skill and reading self-concept over the second grade year. This finding also indicated that students' reading self-concept begins to influence their reading achievement earlier than previous research had indicated. Implications for educational practice and future research will also be discussed. PMID- 20300543 TI - A new nonlinear classifier with a penalized signed fuzzy measure using effective genetic algorithm. AB - This paper proposes a new nonlinear classifier based on a generalized Choquet integral with signed fuzzy measures to enhance the classification accuracy and power by capturing all possible interactions among two or more attributes. This generalized approach was developed to address unsolved Choquet-integral classification issues such as allowing for flexible location of projection lines in n-dimensional space, automatic search for the least misclassification rate based on Choquet distance, and penalty on misclassified points. A special genetic algorithm is designed to implement this classification optimization with fast convergence. Both the numerical experiment and empirical case studies show that this generalized approach improves and extends the functionality of this Choquet nonlinear classification in more real-world multi-class multi-dimensional situations. PMID- 20300542 TI - Experimental and theoretical investigation of chain length and surface coverage on fouling of surface grafted polypeptoids. AB - Numerous strategies exist to prevent biological fouling of surfaces in physiological environments; our strategy focuses on the modification of surfaces with poly-N-substituted glycine oligomers (polypeptoids). We previously reported the synthesis and characterization of three novel polypeptoid polymers that can be used to modify titanium oxide surfaces, rendering the surfaces resistant to adsorption of proteins, to adhesion of mammalian and bacterial cells and to degradation by common protease enzymes. In this study, we investigated the effect of polypeptoid chain length on the antifouling properties of the modified surfaces. For these experiments we used poly(N-methoxyethyl) glycines with lengths between ten and fifty repeat units and determined the influence of chain length on coating thickness and density as well as resistance to protein adsorption and cellular adhesion. Short-term protein resistance remained low for all polymers, as measured by optical waveguide lightmode spectroscopy, while fibroblast adhesion after several weeks indicated reduced fouling resistance for the polypeptoid-modified surfaces with the shortest chain length polymer. Experimental observations were compared to predictions obtained from a molecular theory of polymer and protein adsorption. Good agreement was found between experiment and theory for the chain length dependence of peptoid grafting density, and for protein adsorption as a function of peptoid grafting density. The theoretical predictions provide specific guidelines for the surface coverage for each molecular weight for optimal antifouling. The predictions show the relationship between polymer layer structure and fouling. PMID- 20300544 TI - Autoimmune thyroiditis presenting as palmoplantar keratoderma. AB - Palmoplantar keratoderma is a heterogeneous group of hereditary and acquired disorders characterized by abnormal thickening of palms and soles. Hypothyroidism is an unusual cause of palmoplantar keratoderma, rarely reported in the literature. We report a case of a 43-year-old woman presented with a 3-month history of a diffuse palmoplantar hyperkeratosis unresponsive to topical keratolytics and corticosteroids. Her past medical and family histories were unremarkable. She complained of recent asthenia, mood changes and constipation. Laboratory evaluation revealed an autoimmune thyroiditis with hypothyroidism. Other causes of acquired palmoplantar keratoderma were excluded. After hormonal replacement therapy institution, a gradual improvement of skin condition was observed. The diagnosis of underlying causes for acquired palmoplantar keratoderma can be a difficult task; however its recognition is essential for successful treatment results. Although a very rare association, hypothyroidism must be suspected in patients with acquired palmoplantar keratoderma, particularly when it occurs in association with systemic symptoms. PMID- 20300540 TI - Scorpion venom and the inflammatory response. AB - Scorpion venoms consist of a complex of several toxins that exhibit a wide range of biological properties and actions, as well as chemical compositions, toxicity, and pharmacokinetic and pharmacodynamic characteristics. These venoms are associated with high morbility and mortality, especially among children. Victims of envenoming by a scorpion suffer a variety of pathologies, involving mainly both sympathetic and parasympathetic stimulation as well as central manifestations such as irritability, hyperthermia, vomiting, profuse salivation, tremor, and convulsion. The clinical signs and symptoms observed in humans and experimental animals are related with an excessive systemic host inflammatory response to stings and stings, respectively. Although the pathophysiology of envenomation is complex and not yet fully understood, venom and immune responses are known to trigger the release of inflammatory mediators that are largely mediated by cytokines. In models of severe systemic inflammation produced by injection of high doses of venom or venoms products, the increase in production of proinflammatory cytokines significantly contributes to immunological imbalance, multiple organ dysfunction and death. The cytokines initiate a cascade of events that lead to illness behaviors such as fever, anorexia, and also physiological events in the host such as activation of vasodilatation, hypotension, and increased of vessel permeability. PMID- 20300545 TI - Evidence for vertical transmission of HPV from mothers to infants. AB - Few large studies have evaluated concordance based on a broad spectrum of human papillomavirus (HPV) types in oral and genital specimens of mothers and their recently born infants. This information is important in determining whether HPV vaccines administered prior to pregnancy may be useful for preventing vertical transmission. HPV DNA was positive in 30% of mothers and 1.5% of newborns. Maternal/newborn concordance (HPV+/+ or HPV-/-) was 71%. Among HPV DNA+ mothers, only 3% of their infants were DNA+ and only 1 pair had the same HPV type. Among HPV- women, 0.8% of infants were HPV+. HPV DNA detected in hospitalized newborns reflects current infection transmitted to infants during pregnancy or delivery. None of the mother/baby HPV DNA+ concordance pairs detected viral types found in HPV vaccines suggesting that vaccination prior to pregnancy is unlikely to be efficacious in preventing vertical transmission. PMID- 20300546 TI - An appraisal of anatomical and limited hepatectomy for regional hepatolithiasis. AB - AIM: Determination of first line treatment with limited hepatectomy or Anatomical hepatectomy provides better clinical outcome. METHODS: Immediate and long-term outcomes of 106 patients who underwent partial hepatectomy for RH at our institution from January 2001 to February 2005 were analyzed retrospectively. Clinical end-points included time to recovery of hepatic function, residual stones, infection of the liver remnant, bile leakage, recurrent stones, morbidity, and mortality. RESULTS: LH was performed in 59 patients and AH in 47 patients as first-line treatment. The time of hepatic function recovery was not statistically different between the two groups (P > .05). However, Patients in AH group suffered from less residual stones (P < .05), less infection of the raw surface of liver remnant (P < .05), and less bile leakage (P < .05), with a median follow-up of 40.3 +/- 0.8 months (range 3-48), and AH group suffered a less recurrent stone rate (P < .05). No difference in morbidity, and mortality rates between the two groups. CONCLUSION: AH is a safe and effective treatment for RH, with a fair rate of surgical complications, it should be considered as first-line treatment of RH. PMID- 20300547 TI - Environmental exposure to emissions from petrochemical sites and lung cancer: the lower Mississippi interagency cancer study. AB - To investigate potential links between environmental exposure to petrochemical plant emissions and lung cancer, a population-based case-control study (LMRICS) was conducted in eleven Louisiana parishes bordering the Mississippi River. Cases and age, gender, and race-matched controls were interviewed regarding potential risk factors. Residential history was geocoded to provide indices of long-term proximity to industrial sites. Cases were more likely to have lived near a petrochemical site. Models adjusted for other risk factors, however, showed small or no association with lung cancer (odds ratio for residence within a half-mile of a site = 1.10, 95% confidence interval 0.58-2.08). While associations were strongest for exposures exceeding 15 years, none approached statistical significance and there was no clear dose-response across exposure duration, distance categories, or when sites were grouped according to carcinogenicity rating of chemical releases. Residential proximity to petrochemical plants along the lower Mississippi thus showed no significant association with lung cancer. PMID- 20300549 TI - Monoclonal gammopathy of undetermined significance with amyloid deposition in the lung and non-amyloid eosinophilic deposition in the brain: a case report. AB - Background. Monoclonal gammopathy of undetermined significance (MGUS) is rarely complicated by amyloidosis. Case. A 66-year-old white male presented to the emergency room (ER) after an unwitnessed fall and change in mental status. Patient was awake and alert but not oriented. There was no focal deficit on neurological exam. Past medical history (PMH) included hypertension, hypercholesterolemia, aortic valve replacement (nonmetallic), incomplete heart block controlled by a pacemaker and IgG- IgA type Monoclonal Gammopathy of Undetermined Significance. The MGUS was diagnosed 9 months ago on serum protein electrophoresis (SPEP) as patient was referred to the outpatient clinic for hyperglobulinemia on routine blood work. In ER, a head-computed tomography (CT) revealed multiple parenchymal hemorrhagic lesions suspicious for metastases. A CT chest, abdomen and pelvis revealed numerous ground-glass and solid nodules in the lungs. Lower extremity duplex and transesophageal echocardiogram were negative. Serial blood cultures and serologies for cryptococcus and histoplasmosis, antineutrophil cytoplasmic antibody (ANCA), antinuclear antibody (ANA), rheumatoid factor (RF), cryoglobulin, and antiglomerular basement membrane (anti GBM) antibodies were all negative. CT guided lung biopsy was positive for Thioflavin T amyloid deposits. Brain biopsy was positive for eosinophilic material (similar to the lungs) but negative for Thioflavin T stain. The patient's clinical status continued to deteriorate with cold cyanotic fingers developing on day 12 and a health care acquired pneumonia, respiratory failure, and fungemia on day 18. On day 29, family withdrew life support and denied any autopsies. Conclusion. Described is an atypical course of MGUS complicated by amyloidosis of the lung and nonamyloid eosinophilic deposition in the brain. As MGUS might be complicated by diseases such as amyloidosis and multiple myeloma, a scheduled follow-up of these patients is always necessary. Further research is needed in order to better define the optimal treatment and management strategies of MGUS and its complications. PMID- 20300548 TI - The dual role of calcium as messenger and stressor in cell damage, death, and survival. AB - Ca(2+) is an important second messenger participating in many cellular activities; when physicochemical insults deregulate its delicate homeostasis, it acts as an intrinsic stressor, producing/increasing cell damage. Damage elicits both repair and death responses; intriguingly, in those responses Ca(2+) also participates as second messenger. This delineates a dual role for Ca(2+) in cell stress, making difficult to separate the different and multiple mechanisms required for Ca(2+)-mediated control of cell survival and apoptosis. Here we attempt to disentangle the two scenarios, examining on the one side, the events implicated in deregulated Ca(2+) toxicity and the mechanisms through which this elicits reparative or death pathways; on the other, reviewing the role of Ca(2+) as a messenger in the transduction of these same signaling events. PMID- 20300550 TI - Ischemic Stroke of the Artery of Percheron with Normal Initial MRI: A Case Report. AB - The artery of Percheron is a solitary trunk representing an uncommon anatomic variant that provides bilateral arterial supply to the paramedian thalami and the rostral midbrain. Occlusion of this artery results in bilateral thalamic and mesencephalic infarctions. The clinical diagnosis is difficult because the complex anatomy causes large clinical variability. We report a case of a comatose patient with normal early head-computed tomography and magnetic resonance imaging. A bilateral paramedian thalamic infarct due to an occlusion of the artery of Percheron was revealed two days later by a new head computed tomography. To our knowledge, this is the first report in the literature of a symptomatic patient presenting an acute Percheron stroke with normal early brain magnetic resonance imaging. Our case indicates that a normal initial magnetic resonance imaging cannot formally eliminate the diagnosis of acute stroke of the artery of Percheron. We discuss the causes of noncontributive brain magnetic resonance imaging at the onset of this acute Percheron stroke and the alternative diagnosis and therapy methods. PMID- 20300551 TI - Aberrant methylation of thrombospondin-1 and its association with reduced expression in gastric cardia adenocarcinoma. AB - AIM: Investigate the promoter methylation of the Thrombospondin-1 (TSP1) gene in gastric cardia adenocarcinoma (GCA). METHODS: MSP approach, immunohistochemistry method, and RT-PCR were used respectively to examine the promoter methylation of TSP1, its protein and mRNA expression in tumors and corresponding normal tissues. The expression and concentration of TGF-beta1 were examined respectively by immunohistochemistry and ELISA method. The status of T cell immunity was examined by Flow cytometry analysis. RESULTS: TSP1 was methylated in 34/96 (35.4%) tumor specimens, which was significantly higher than that in corresponding normal tissues (P < .001). Protein and mRNA expression of TSP1 in GCA tumor tissues were reduced significantly and were associated with TSP1 methylation. The protein expression of TGF-beta1 was significantly higher in tumor tissues (P < .001) and was associated with TNM stage and histological differentiation. The concentration of active and total TGF-beta1 did not show significant difference between the GCA patients with hypermethylation of TSP1 and without methylation of TSP1 (P > .05). The function of T cell immunity was significantly different between the GCA patients with hypermethylation of TSP1 and without methylation of TSP1. CONCLUSIONS: Epigenetic silencing of TSP1 gene by promoter hypermethylation may play an important role in GCA. PMID- 20300552 TI - Disrupting ovarian cancer metastatic colonization: insights from metastasis suppressor studies. AB - Ovarian cancer affects approximately 25,000 women in the United States each year and remains one of the most lethal female malignancies. A standard approach to therapy is surgical cytoreduction, after which the remaining microscopic residual disease is treated with chemotherapy. The vast majority of patients have disease recurrence, underscoring the crucial need for approaches to control the regrowth, or colonization, of tissues after local treatment. Improved therapies require mechanistic information about the process of metastatic colonization, the final step in metastasis, in which cancer cells undergo progressive growth at secondary sites. Studies of metastasis suppressors are providing insights into events controlling metastatic colonization. This paper reviews our laboratory's approach to the identification, characterization, and functional testing of the JNKK1/MKK4 metastasis suppressor in ovarian cancer metastatic colonization. Specifically, we demonstrate that interaction of ovarian caner cells with the omental microenvironment activates JNKK1/MKK4 resulting in decreased proliferation without affecting apoptosis. The potential role of the omental microenvironment, specifically milky spot structures, is also described. It is our goal to provide this work as a usable paradigm that will enable others to study metastasis suppressors in clinical and experimental ovarian cancer metastases. PMID- 20300553 TI - A Bayesian Maximum Entropy approach to address the change of support problem in the spatial analysis of childhood asthma prevalence across North Carolina. AB - The spatial analysis of data observed at different spatial observation scales leads to the change of support problem (COSP). A solution to the COSP widely used in linear spatial statistics consists in explicitly modeling the spatial autocorrelation of the variable observed at different spatial scales. We present a novel approach that takes advantage of the non-linear Bayesian Maximum Entropy (BME) extension of linear spatial statistics to address the COSP directly without relying on the classical linear approach. Our procedure consists in modeling data observed over large areas as soft data for the process at the local scale. We demonstrate the application of our approach to obtain spatially detailed maps of childhood asthma prevalence across North Carolina (NC). Because of the high prevalence of childhood asthma in NC, the small number problem is not an issue, so we can focus our attention solely to the COSP of integrating prevalence data observed at the county-level together with data observed at a targeted local scale equivalent to the scale of school-districts. Our spatially detailed maps can be used for different applications ranging from exploratory and hypothesis generating analyses to targeting intervention and exposure mitigation efforts. PMID- 20300554 TI - Simulating Monovalent and Divalent Ions in Aqueous Solution Using a Drude Polarizable Force Field. AB - An accurate representation of ion solvation in aqueous solution is critical for meaningful computer simulations of a broad range of physical and biological processes. Polarizable models based on classical Drude oscillators are introduced and parametrized for a large set of monoatomic ions including cations of the alkali metals (Li(+), Na(+), K(+), Rb(+) and Cs(+)) and alkaline earth elements (Mg(2+), Ca(2+), Sr(2+) and Ba(2+)) along with Zn(2+) and halide anions (F(-), Cl(-), Br(-) and I(-)). The models are parameterized, in conjunction with the polarizable SWM4-NDP water model [Lamoureux et al., Chem. Phys. Lett. 418, 245 (2006)], to be consistent with a wide assortment of experimentally measured aqueous bulk thermodynamic properties and the energetics of small ion-water clusters. Structural and dynamic properties of the resulting ion models in aqueous solutions at infinite dilution are presented. PMID- 20300555 TI - Is There a Predisposition Gene for Ewing's Sarcoma? AB - Ewing's sarcoma is a highly malignant tumor of children and young adults. The molecular mechanisms that underlie Ewing's Sarcoma development are beginning to be understood. For example, most cases of this disease harbor somatic chromosomal translocations that fuse the EWSR1 gene on chromosome 22 with members of the ETS family. While some cooperative genetic events have been identified, such as mutations in TP53 or deletions of the CDKN2A locus, these appear to be absent in the vast majority of cases. It is therefore uncertain whether EWS/ETS translocations are the only consistently present alteration in this tumor, or whether there are other recurrent abnormalities yet to be discovered. One method to discover such mutations is to identify familial cases of Ewing's sarcoma and to then map the susceptibility locus using traditional genetic mapping techniques. Although cases of sibling pairs with Ewing's sarcoma exist, familial cases of Ewing's sarcoma have not been reported. While Ewing's sarcoma has been reported as a 2nd malignancy after retinoblastoma, significant associations of Ewing's sarcoma with classic tumor susceptibility syndromes have not been identified. We will review the current evidence, or lack thereof, regarding the potential of a heritable condition predisposing to Ewing's sarcoma. PMID- 20300556 TI - Ureteroiliac artery fistula in a young woman with short bowel syndrome for radiation enteritis. AB - Ureteral-iliac artery fistula is a rare and potentially life-threatening complication, typically occurring after radiation therapy in already surgically treated cancer patients. This case report describes the diagnostic challenges and the successful management, with the positioning of an intra-arterial prosthesis, of a fistula between the internal iliac artery and the left ureter presenting as massive hematuria in a young woman with history of total colectomy and pelvic radiotherapy for rectal cancer and subsequent wide ileal resections and bilateral ureteral stent positioning for radiation enteritis. Ureteroiliac artery fistulas require a prompt diagnosis and intervention, to avoid life threatening clinical events. PMID- 20300557 TI - Combining area-based and individual-level data in the geostatistical mapping of late-stage cancer incidence. AB - This paper presents a geostatistical approach to incorporate individual-level data (e.g. patient residences) and area-based data (e.g. rates recorded at census tract level) into the mapping of late-stage cancer incidence, with an application to breast cancer in three Michigan counties. Spatial trends in cancer incidence are first estimated from census data using area-to-point binomial kriging. This prior model is then updated using indicator kriging and individual-level data. Simulation studies demonstrate the benefits of this two-step approach over methods (kernel density estimation and indicator kriging) that process only residence data. PMID- 20300558 TI - Left Ventricle Segmentation Using Model Fitting and Active Surfaces. AB - A method to perform 4D (3D over time) segmentation of the left ventricle of a mouse heart using a set of B mode cine slices acquired in vivo from a series of short axis scans is described. We incorporate previously suggested methods such as temporal propagation, the gradient vector flow active surface, superquadric models, etc. into our proposed 4D segmentation of the left ventricle. The contributions of this paper are incorporation of a novel despeckling method and the use of locally fitted superellipsoid models to provide a better initialization for the active surface segmentation algorithm. Average distances of the improved surface segmentation to a manually segmented surface throughout the entire cardiac cycle and cross-sectional contours are provided to demonstrate the improvements produced by the proposed 4D segmentation. PMID- 20300559 TI - An evolutionary examination of telemedicine: a health and computer-mediated communication perspective. AB - Telemedicine, the use of advanced communication technologies in the healthcare context, has a rich history and a clear evolutionary course. In this paper, the authors identify telemedicine as operationally defined, the services and technologies it comprises, the direction telemedicine has taken, along with its increased acceptance in the healthcare communities. The authors also describe some of the key pitfalls warred with by researchers and activists to advance telemedicine to its full potential and lead to an unobstructed team of technicians to identify telemedicine's diverse utilities. A discussion and future directions section is included to provide fresh ideas to health communication and computer-mediated scholars wishing to delve into this area and make a difference to enhance public understanding of this field. PMID- 20300560 TI - Computation of nonparametric convex hazard estimators via profile methods. AB - This paper proposes a profile likelihood algorithm to compute the nonparametric maximum likelihood estimator of a convex hazard function. The maximisation is performed in two steps: First the support reduction algorithm is used to maximise the likelihood over all hazard functions with a given point of minimum (or antimode). Then it is shown that the profile (or partially maximised) likelihood is quasi-concave as a function of the antimode, so that a bisection algorithm can be applied to find the maximum of the profile likelihood, and hence also the global maximum. The new algorithm is illustrated using both artificial and real data, including lifetime data for Canadian males and females. PMID- 20300561 TI - Novel mutations in MERTK associated with childhood onset rod-cone dystrophy. AB - PURPOSE: To report the clinical phenotype in patients with a retinal dystrophy associated with novel mutations in the MER tyrosine kinase (MERTK) gene. METHODS: A consanguineous family of Middle Eastern origin was identified, and affected members underwent a full clinical evaluation. Linkage analysis was performed using the Affymetrix 50K chip. Regions of homozygosity were identified. The positional candidate genes protocadherin 21 (PCDH21), retinal G protein-coupled receptor (RGR), and MERTK were polymerase chain reaction (PCR) amplified and sequenced. Long-range PCR was performed to characterize the deletion. Two hundred and ninety-two probands with autosomal recessive, childhood onset, retinal dystrophies were analyzed using the Asper Ophthalmics Leber congenital amaurosis chip to screen for known MERTK mutations. RESULTS: Analysis of a 50K-Affymetrix whole genome scan identified three regions of homozygosity on chromosomes 2 and 10. Screening of the candidate gene MERTK showed a possible deletion of exon 8. Long-range PCR identified a ~9 kb deletion within MERTK that removes exon 8. Screening of DNA from a panel of Saudi Arabian patients with autosomal recessive retinitis pigmentosa identified a second consanguineous family with the same mutation. One patient with a known MERTK mutation (p.R651X) was identified using the Asper Ophthalmics Leber congenital amaurosis chip. Further screening of the gene identified a second novel splice site mutation in intron 1. The phenotype associated with these identified MERTK mutations is of a childhood onset rod-cone dystrophy with early macular atrophy. The optical coherence tomography (OCT) appearance is distinctive with evidence of debris beneath the sensory retina. CONCLUSIONS: Mutations in MERTK are a rare cause of retinal dystrophy. Non homologous recombination between Alu Y repeats near or within disease genes may be an important cause of retinal dystrophies. PMID- 20300562 TI - A monogenic dominant mutation in Rom1 generated by N-ethyl-N-nitrosourea mutagenesis causes retinal degeneration in mice. AB - PURPOSE: To characterize an N-ethyl-N-nitrosourea-induced dominant mouse mutant, M-1156, that exhibits progressive retinal degeneration and to investigate the pathogenesis of the retinal phenotype in the mutant. METHODS: A positional candidate gene approach was used to identify the causative gene in the M-1156 mutant. Funduscopic examination, light microscopy, transmission electron microscopy, and electroretinography were performed to analyze the M-1156 phenotype. Real-time quantitative PCR, immunohistochemistry, and western blotting were also performed. RESULTS: Linkage analysis enabled the mutant gene to be mapped to a region of chromosome 19 containing Rom1, which encodes rod outer segment membrane protein 1. Sequence analysis demonstrated that the mutation consisted of a single base T-->C substitution at position 1,195 in Rom1 (M96760, National Center for Biotechnology Information [NCBI]) and that the mutant allele was expressed. A putative missense mutation designated Rom1(Rgsc1156) that was identified in the M-1156 mutant mouse causes a Trp to Arg substitution at position 182 in the translated protein. Rom1(Rgsc1156) heterozygotes were found to have a mottled retina and narrowed arteries in the fundus oculi. Photomicrographs of the retina revealed significant differences among the genotypes in the thickness of the outer nuclear layer and in the length of the outer segments of the photoreceptors. The alterations were more marked in the homozygotes than in the heterozygotes. Electron micrographs showed that the diameters of the discs varied in the heterozygotes and that the discs were more compactly stacked than in the wild type. There were significant differences among the genotypes in the amplitude of the a-wave in single-flash electroretinograms, but there were no significant differences among the photopic electroretinograms. Real-time quantitative PCR showed that there were no significant differences among the genotypes in Rom1 or peripherin/rds (Prph2) mRNA levels relative to the rhodopsin (Rho) mRNA level. Rom1 and Prph2 immunoreactivity were decreased in the retinas of the Rom1(Rgsc1156) mutants. Semiquantitative western blot analysis of retinas from 3-week-old Rom1(Rgsc1156) mutants demonstrated significant decreases in Rom1, Prph2, and Rho protein levels in all of the genotypes. CONCLUSIONS: The Trp182Arg substitution in Rom1(Rgsc1156) mutants causes retinal degeneration. The results suggested that Trp182Arg mutant Rom1 causes a decrease in the levels of wild-type Prph2 and Rom1, which in turn cause a reduction in the level of Prph2 containing tetramers in the disc rim region and ultimately result in unstable, disorganized outer segments and photoreceptor degeneration. PMID- 20300563 TI - FOXO1 plays an essential role in apoptosis of retinal pericytes. AB - PURPOSE: An early and significant event in diabetic retinopathy is the loss of retinal microvascular pericytes. Studies were performed to investigate pathways through which an advanced glycation endproduct and tumor necrosis factor (TNF) alpha stimulate apoptosis in retinal pericytes through the activation of the pro apoptotic transcription factor Forkhead box O1 (FOXO1). METHODS: Human retinal pericytes were stimulated by carboxymethyllysine (CML)-collagen, an advanced glycation endproduct, or TNF-alpha in vitro. Apoptosis was assessed by measuring cytoplasmic histone-associated DNA. The role of FOXO1 was examined by RNA interference (RNAi), and specific inhibitors were used to investigate the role of p38 and Jun N-terminal kinase mitogen-activated protein kinase (JNK MAP) kinases, Akt, and nuclear factor kappa B (NF-kappaB). Caspase-3 activity was measured with a luminescent substrate, and FOXO1 DNA-binding activity was measured by electrophoretic mobility shift assay (EMSA). RESULTS: TNF-alpha and CML-collagen but not control collagen stimulated apoptosis, caspase-3 activity, and FOXO1 DNA binding activity in pericytes. Silencing FOXO1 by small interfering RNA prevented apoptosis of pericytes in response to both TNF-alpha and CML-collagen. By use of specific inhibitors, we demonstrated that both FOXO1 activation and subsequent apoptosis was mediated, in part, by p38 and JNK MAP kinases. In contrast Akt and NF-kappaB inhibitors had the opposite effect on pericyte apoptosis. CONCLUSIONS: The results demonstrate pathways through which two different mediators, TNF-alpha and an advanced glycation endproduct, can induce pericyte apoptosis through activation of the transcription factor FOXO1. PMID- 20300564 TI - Evaluation of the X-linked modifier loci for Leber hereditary optic neuropathy with the G11778A mutation in Chinese. AB - PURPOSE: To test the association of the X-chromosome regions (Xp21.1-q21.2 and Xq25-27.2) with Leber hereditary optic neuropathy (LHON) in Chinese patients. METHODS: One hundred and seventy-five male LHON patients with the G11778A mutation and 100 unrelated normal males participated. Twelve microsatellite markers and four single-nucleotide polymorphisms (SNPs) were genotyped for patients and controls. A chi(2) or Fisher's exact test was used to compare the frequencies of genotypes as well as haplotypes in the two groups. RESULTS: Significant differences between patients and controls were found in two isolated microsatellite markers (DXS6803: chi(2)=37.17, p=2.45 x 10(-5); DXS984: chi(2)=33.88, p=1.66 x 10(-6)) based on genotype frequencies. However, no significant differences for genotype and haplotype frequencies were found in the other 14 markers located in the two reported regions of Xp21.1-q21.2 and Xq25 27.2. CONCLUSIONS: Our results provide suggestive evidence of X-linked modifiers on the expression of LHON. Further studies are needed to identify the exact nuclear genes that might affect LHON expression. PMID- 20300565 TI - TRPM1 mutations are associated with the complete form of congenital stationary night blindness. AB - PURPOSE: To identify human transient receptor potential cation channel, subfamily M, member 1 (TRPM1) gene mutations in patients with congenital stationary night blindness (CSNB). METHODS: We analyzed four different Japanese patients with complete CSNB in whom previous molecular examination revealed no mutation in either nyctalopin (NYX) or glutamate receptor, metabotropic 6 (GRM6). The ophthalmologic examination included best-corrected visual acuity, refraction, biomicroscopy, ophthalmoscopy, fundus photography, Goldmann kinetic perimetry, color vision tests, and electroretinography (ERG). Exons 2 through 27 and the exon-intron junction regions of human TRPM1 were sequenced. RESULTS: Five different mutations in human TRPM1 were identified. Mutations were present in three unrelated patients with complete CSNB. All three patients were compound heterozygotes. Fundus examination revealed no abnormalities other than myopic changes, and the single bright-flash, mixed rod-cone ERG showed a "negative-type" configuration with a reduced normal a-wave and a significantly reduced b-wave amplitude. Our biochemical and cell biologic analyses suggest that the two identified IVS mutations lead to abnormal TRPM1 protein production, and imply that the two identified missense mutations lead to the mislocalization of the TRPM1 protein in bipolar cells (BCs). CONCLUSIONS: Human TRPM1 mutations are associated with the complete form of CSNB in Japanese patients, suggesting that TRPM1 plays an essential role in mediating the photoresponse in ON BCs in humans as well as in mice. PMID- 20300566 TI - Decreasing the homodimer interaction: a common mechanism shared by the deltaG91 mutation and deamidation in betaA3-crystallin. AB - PURPOSE: Cataracts can be broadly divided into two types: congenital cataracts and age-related cataracts. DeltaG91 is a previously discovered congenital mutation in betaA3-crystallin that impairs protein solubility. On the other hand, the deamidation of beta-crystallin is a significant feature in aged and cataractous lenses. Several deamidation sites were also identified in betaA3 crystallin. The present study is to compare the functional consequence of DeltaG91 mutation and the deamidation of betaA3-crystallin in terms of folding properties and protein-protein interaction. METHODS: Protein secondary structure and hydrophobic properties were investigated by in silica analysis of the wild type and mutants sequences. Full-length betaA3-crystallin was cloned into a mammalian two-hybrid system in order to investigate protein-protein interactions. Deletion and deamidation were introduced by site-directed mutagenesis protocols. Both the Q85 and Q180 deamidation sites were substituted with glutamic acid residues to mimic deamidation. Different combinations of plasmid constructs were transfected in HeLa cells, and changes of protein-protein interactions were analyzed by the luciferase assay. RESULTS: Bioinformatics prediction suggested that DeltaG91 mutation alters both the predicted secondary structure and hydrophobic character of betaA3-crystallin, while deamidation only exhibits minimal effects. Mammalian two-hybrid results indicated that both DeltaG91 mutation and Q85/Q180 deamidation could significantly decrease the interaction of the betaA3-crystallin homodimer. CONCLUSION: Our results provided evidence that both mutations involved in congenital cataracts and deamidation in aged lenses commonly altered protein-protein interaction between human lens betaA3 crystallins, which may lead to protein insolubilization and contribute to cataracts. PMID- 20300567 TI - Alterations in lenticular proteins during ageing and selenite-induced cataractogenesis in Wistar rats. AB - PURPOSE: To determine putative alterations in the major lenticular proteins in Wistar rats of different ages and to compare these alterations with those occurring in rats with selenite-induced cataract. METHODS: Lenticular transparency was determined by morphological examination using slit-lamp biomicroscopy. Alterations in lenticular protein were determined by sodium dodecyl sulfate-PAGE (SDS-PAGE) and confirmed immunologically by western blot. RESULTS: Morphological examination did not reveal observable opacities in the lenses of the rats of different age groups; however, dense nuclear opacities were noted in lenses of rats in the selenite-cataract group. Western blot assays revealed age-related changes in soluble and urea-soluble lenticular proteins. Decreased alphaA- and betaB1-crystallins in the soluble fraction and aggregation of alphaA-crystallin, in addition to the degraded fragment of betaB1-crystallin, in the urea-soluble fraction appeared to occur in relation to increasing age of the rats from which the lenses were taken; similarly, cytoskeletal proteins appeared to decline with increasing age. The lenses from rats in the selenite cataract group exhibited similar changes, except that there was also high molecular weight aggregation of alphaA-crystallin. CONCLUSIONS: The results of this study suggest that there is loss, as well as aggregation, of alphaA crystallin in the aging rat lens, although there is no accompanying loss of lenticular transparency. PMID- 20300568 TI - Mitogen-activated protein kinases in the porcine retinal arteries and neuroretina following retinal ischemia-reperfusion. AB - PURPOSE: The aim of the present study was to examine changes in the expression of intracellular signal-transduction pathways, specifically mitogen-activated protein kinases, following retinal ischemia-reperfusion. METHODS: Retinal ischemia was induced by elevating the intraocular pressure in porcine eyes, followed by 5, 12, or 20 h of reperfusion. The results were compared to those of the sham- operated fellow eye. The retinal arteries and neuroretina were isolated separately and examined. Tissue morphology and DNA fragmentation were studied using histology. Extracellular signal-regulated kinase 1 and 2 (ERK1/2), p38, c junNH(2)-terminal kinases (JNK), and c-jun protein and mRNA expression were examined using immunofluorescence staining, western blot, and real-time PCR techniques. RESULTS: Pyknotic cell nuclei, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)-positive cells, and glial fibrillary acidic protein mRNA expression were increased in ischemia, suggesting injury. Phosphorylated ERK1/2 protein levels were increased in the neuroretina following ischemia, while mRNA levels were unaltered. p38 protein and mRNA levels were not affected by ischemia. Immunofluorescence staining for phosphorylated p38 was especially intense in the retinal blood vessels, while only weak in the neuroretina. Phosphorylated JNK protein and mRNA were slightly decreased in ischemia. Phosphorylated c-jun protein and mRNA levels were higher in the neuroretina after ischemia-reperfusion. CONCLUSIONS: Retinal ischemia-reperfusion alters expression of mitogen-activated protein kinases, particularly ERK1/2, in the neuroretina and retinal arteries. The development of pharmacological treatment targeting these intracellular transduction pathways may prevent injury to the eye following retinal circulatory failure. PMID- 20300569 TI - Informal urban settlements and cholera risk in Dar es Salaam, Tanzania. AB - BACKGROUND: As a result of poor economic opportunities and an increasing shortage of affordable housing, much of the spatial growth in many of the world's fastest growing cities is a result of the expansion of informal settlements where residents live without security of tenure and with limited access to basic infrastructure. Although inadequate water and sanitation facilities, crowding and other poor living conditions can have a significant impact on the spread of infectious diseases, analyses relating these diseases to ongoing global urbanization, especially at the neighborhood and household level in informal settlements, have been infrequent. To begin to address this deficiency, we analyzed urban environmental data and the burden of cholera in Dar es Salaam, Tanzania. METHODOLOGY/PRINCIPAL FINDINGS: Cholera incidence was examined in relation to the percentage of a ward's residents who were informal, the percentage of a ward's informal residents without an improved water source, the percentage of a ward's informal residents without improved sanitation, distance to the nearest cholera treatment facility, population density, median asset index score in informal areas, and presence or absence of major roads. We found that cholera incidence was most closely associated with informal housing, population density, and the income level of informal residents. Using data available in this study, our model would suggest nearly a one percent increase in cholera incidence for every percentage point increase in informal residents, approximately a two percent increase in cholera incidence for every increase in population density of 1000 people per km(2) in Dar es Salaam in 2006, and close to a fifty percent decrease in cholera incidence in wards where informal residents had minimally improved income levels, as measured by ownership of a radio or CD player on average, in comparison to wards where informal residents did not own any items about which they were asked. In this study, the range of access to improved sanitation and improved water sources was quite narrow at the ward level, limiting our ability to discern relationships between these variables and cholera incidence. Analysis at the individual household level for these variables would be of interest. CONCLUSIONS/SIGNIFICANCE: Our results suggest that ongoing global urbanization coupled with urban poverty will be associated with increased risks for certain infectious diseases, such as cholera, underscoring the need for improved infrastructure and planning as the world's urban population continues to expand. PMID- 20300570 TI - A comparative proteomic analysis reveals a new bi-lobe protein required for bi lobe duplication and cell division in Trypanosoma brucei. AB - A Golgi-associated bi-lobed structure was previously found to be important for Golgi duplication and cell division in Trypanosoma brucei. To further understand its functions, comparative proteomics was performed on extracted flagellar complexes (including the flagellum and flagellum-associated structures such as the basal bodies and the bi-lobe) and purified flagella to identify new bi-lobe proteins. A leucine-rich repeats containing protein, TbLRRP1, was characterized as a new bi-lobe component. The anterior part of the TbLRRP1-labeled bi-lobe is adjacent to the single Golgi apparatus, and the posterior side is tightly associated with the flagellar pocket collar marked by TbBILBO1. Inducible depletion of TbLRRP1 by RNA interference inhibited duplication of the bi-lobe as well as the adjacent Golgi apparatus and flagellar pocket collar. Formation of a new flagellum attachment zone and subsequent cell division were also inhibited, suggesting a central role of bi-lobe in Golgi, flagellar pocket collar and flagellum attachment zone biogenesis. PMID- 20300571 TI - Morbid obesity as a risk factor for hospitalization and death due to 2009 pandemic influenza A(H1N1) disease. AB - BACKGROUND: Severe illness due to 2009 pandemic A(H1N1) infection has been reported among persons who are obese or morbidly obese. We assessed whether obesity is a risk factor for hospitalization and death due to 2009 pandemic influenza A(H1N1), independent of chronic medical conditions considered by the Advisory Committee on Immunization Practices (ACIP) to increase the risk of influenza-related complications. METHODOLOGY/PRINCIPAL FINDINGS: We used a case cohort design to compare cases of hospitalizations and deaths from 2009 pandemic A(H1N1) influenza occurring between April-July, 2009, with a cohort of the U.S. population estimated from the 2003-2006 National Health and Nutrition Examination Survey (NHANES); pregnant women and children <2 years old were excluded. For hospitalizations, we defined categories of relative weight by body mass index (BMI, kg/m(2)); for deaths, obesity or morbid obesity was recorded on medical charts, and death certificates. Odds ratio (OR) of being in each BMI category was determined; normal weight was the reference category. Overall, 361 hospitalizations and 233 deaths included information to determine BMI category and presence of ACIP-recognized medical conditions. Among >or=20 year olds, hospitalization was associated with being morbidly obese (BMI>or=40) for individuals with ACIP-recognized chronic conditions (OR = 4.9, 95% CI 2.4-9.9) and without ACIP-recognized chronic conditions (OR = 4.7, 95%CI 1.3-17.2). Among 2-19 year olds, hospitalization was associated with being underweight (BMIor=20 years without ACIP-recognized chronic medical conditions death was associated with obesity (OR = 3.1, 95%CI: 1.5-6.6) and morbid obesity (OR = 7.6, 95%CI 2.1-27.9). CONCLUSIONS/SIGNIFICANCE: Our findings support observations that morbid obesity may be associated with hospitalization and possibly death due to 2009 pandemic H1N1 infection. These complications could be prevented by early antiviral therapy and vaccination. PMID- 20300572 TI - FaaPred: a SVM-based prediction method for fungal adhesins and adhesin-like proteins. AB - Adhesion constitutes one of the initial stages of infection in microbial diseases and is mediated by adhesins. Hence, identification and comprehensive knowledge of adhesins and adhesin-like proteins is essential to understand adhesin mediated pathogenesis and how to exploit its therapeutic potential. However, the knowledge about fungal adhesins is rudimentary compared to that of bacterial adhesins. In addition to host cell attachment and mating, the fungal adhesins play a significant role in homotypic and xenotypic aggregation, foraging and biofilm formation. Experimental identification of fungal adhesins is labor- as well as time-intensive. In this work, we present a Support Vector Machine (SVM) based method for the prediction of fungal adhesins and adhesin-like proteins. The SVM models were trained with different compositional features, namely, amino acid, dipeptide, multiplet fractions, charge and hydrophobic compositions, as well as PSI-BLAST derived PSSM matrices. The best classifiers are based on compositional properties as well as PSSM and yield an overall accuracy of 86%. The prediction method based on best classifiers is freely accessible as a world wide web based server at http://bioinfo.icgeb.res.in/faap. This work will aid rapid and rational identification of fungal adhesins, expedite the pace of experimental characterization of novel fungal adhesins and enhance our knowledge about role of adhesins in fungal infections. PMID- 20300573 TI - Reconstitution of mammary epithelial morphogenesis by murine embryonic stem cells undergoing hematopoietic stem cell differentiation. AB - BACKGROUND: Mammary stem cells are maintained within specific microenvironments and recruited throughout lifetime to reconstitute de novo the mammary gland. Mammary stem cells have been isolated through the identification of specific cell surface markers and in vivo transplantation into cleared mammary fat pads. Accumulating evidence showed that during the reformation of mammary stem cell niches by dispersed epithelial cells in the context of the intact epithelium-free mammary stroma, non-mammary epithelial cells may be sequestered and reprogrammed to perform mammary epithelial cell functions and to adopt mammary epithelial characteristics during reconstruction of mammary epithelium in regenerating mammary tissue in vivo. METHODOLOGY/PRINCIPAL FINDINGS: To examine whether other types of progenitor cells are able to contribute to mammary branching morphogenesis, we examined the potential of murine embryonic stem (mES) cells, undergoing hematopoietic differentiation, to support mammary reconstitution in vivo. We observed that cells from day 14 embryoid bodies (EBs) under hematopoietic differentiation condition, but not supernatants derived from these cells, when transplanted into denuded mammary fat pads, were able to contribute to both the luminal and myoepithelial lineages in branching ductal structures resembling the ductal-alveolar architecture of the mammary tree. No teratomas were observed when these cells were transplanted in vivo. CONCLUSIONS/SIGNIFICANCE: Our data provide evidence for the dominance of the tissue-specific mammary stem cell niche and its role in directing mES cells, undergoing hematopoietic differentiation, to reprogram into mammary epithelial cells and to promote mammary epithelial morphogenesis. These studies should also provide insights into regeneration of damaged mammary gland and the role of the mammary microenvironment in reprogramming cell fate. PMID- 20300574 TI - Predictors of HIV testing among patients with tuberculosis in North West Ethiopia: a case-control study. AB - BACKGROUND: The acceptance of HIV testing among patients with tuberculosis (TB) is low in Ethiopia. The purpose of this study was to assess predictors of acceptance of HIV testing among patients with TB in North Ethiopia. METHODS: A case control study was conducted in eight randomly selected health facilities in North Ethiopia from February 5 to March 11, 2009. A total of 282 participants (188 controls and 94 cases) were included in the study. Cases were TB patients who refused to be tested for HIV. We used quantitative and qualitative methods of data collection. For the quantitative survey, cases and controls were interviewed by trained nurses using a pre-tested and structured questionnaire. In-depth interviews were conducted with 5 nurse counselors and 15 TB patients. Bivariate and multivariate analysis was done using SPSS 16.0 statistical software. RESULTS: The uptake of HIV testing among TB patients in the study health facilities was 70.6%. The rate of TB/HIV co-infection in those who were tested was 36.2%. From the source population, a total of 282 participants were included in the study. TB patients who had formal education [OR = 2.35, (95%CI: 1.33, 4.13)], high awareness about the benefits of HIV counseling and testing [OR = 3.14, 95%CI: 1.77, 5.50)], and a low stigmatized attitude [OR = 3.16, 95%CI: 1.79, 5.59)] were more likely to accept HIV testing. The qualitative study also revealed that low awareness and stigma were the major reasons for non-acceptance of HIV testing. CONCLUSION: "Knowledge and attitude" factors were the major barriers for HIV testing. Tailored training should be given to TB patients and the community concerning the benefits of HIV testing. During counseling sessions, health workers should focus on barriers of uptake of HIV testing such as stigma and discrimination. PMID- 20300575 TI - Lifting without seeing: the role of vision in perceiving and acting upon the size weight illusion. AB - BACKGROUND: Our expectations of an object's heaviness not only drive our fingertip forces, but also our perception of heaviness. This effect is highlighted by the classic size-weight illusion (SWI), where different-sized objects of identical mass feel different weights. Here, we examined whether these expectations are sufficient to induce the SWI in a single wooden cube when lifted without visual feedback, by varying the size of the object seen prior to the lift. METHODOLOGY/PRINCIPAL FINDINGS: Participants, who believed that they were lifting the same object that they had just seen, reported that the weight of the single, standard-sized cube that they lifted on every trial varied as a function of the size of object they had just seen. Seeing the small object before the lift made the cube feel heavier than it did after seeing the large object. These expectations also affected the fingertip forces that were used to lift the object when vision was not permitted. The expectation-driven errors made in early trials were not corrected with repeated lifting, and participants failed to adapt their grip and load forces from the expected weight to the object's actual mass in the same way that they could when lifting with vision. CONCLUSIONS/SIGNIFICANCE: Vision appears to be crucial for the detection, and subsequent correction, of the ostensibly non-visual grip and load force errors that are a common feature of this type of object interaction. Expectations of heaviness are not only powerful enough to alter the perception of a single object's weight, but also continually drive the forces we use to lift the object when vision is unavailable. PMID- 20300577 TI - Enteroaggregative Escherichia coli: An Emerging Enteric Food Borne Pathogen. AB - Enteroaggregative Escherichia coli (EAEC) are quite heterogeneous category of an emerging enteric pathogen associated with cases of acute or persistent diarrhea worldwide in children and adults, and over the past decade has received increasing attention as a cause of watery diarrhea, which is often persistent. EAEC infection is an important cause of diarrhea in outbreak and non-outbreak settings in developing and developed countries. Recently, EAEC has been implicated in the development of irritable bowel syndrome, but this remains to be confirmed. EAEC is defined as a diarrheal pathogen based on its characteristic aggregative adherence (AA) to HEp-2 cells in culture and its biofilm formation on the intestinal mucosa with a "stacked-brick" adherence phenotype, which is related to the presence of a 60 MDa plasmid (pAA). At the molecular level, strains demonstrating the aggregative phenotype are quite heterogeneous; several virulence factors are detected by polymerase chain reaction; however, none exhibited 100% specificity. Although several studies have identified specific virulence factor(s) unique to EAEC, the mechanism by which EAEC exerts its pathogenesis is, thus, far unknown. The present review updates the current knowledge on the epidemiology, chronic complications, detection, virulence factors, and treatment of EAEC, an emerging enteric food borne pathogen. PMID- 20300578 TI - Cytokines and other mediators in alopecia areata. AB - Alopecia areata, a disease of the hair follicles with multifactorial etiology and a strong component of autoimmune origin, has been extensively studied as far as the role of several cytokines is concerned. So far, IFN-gamma, interleukins, TNF alpha, are cytokines that are well known to play a major role in the pathogenesis of the disease, while several studies have shown that many more pathways exist. Among them, MIG, IP-10, BAFF, HLA antigens, MIG, as well as stress hormones are implicated in disease onset and activity. Within the scope of this paper, the authors attempt to shed light upon the complexity of alopecia areata underlying mechanisms and indicate pathways that may suggest future treatments. PMID- 20300579 TI - A Dominant-Negative PPARgamma Mutant Promotes Cell Cycle Progression and Cell Growth in Vascular Smooth Muscle Cells. AB - PPARgamma ligands have been shown to have antiproliferative effects on many cell types. We herein report that a synthetic dominant-negative (DN) PPARgamma mutant functions like a growth factor to promote cell cycle progression and cell proliferation in human coronary artery smooth muscle cells (CASMCs). In quiescent CASMCs, adenovirus-expressed DN-PPARgamma promoted G1-->S cell cycle progression, enhanced BrdU incorporation, and increased cell proliferation. DN-PPARgamma expression also markedly enhanced positive regulators of the cell cycle, increasing Rb and CDC2 phosphorylation and the expression of cyclin A, B1, D1, and MCM7. Conversely, overexpression of wild-type (WT) or constitutively-active (CA) PPARgamma inhibited cell cycle progression and the activity and expression of positive regulators of the cell cycle. DN-PPARgamma expression, however, did not up-regulate positive cell cycle regulators in PPARgamma-deficient cells, strongly suggesting that DN-PPARgamma effects on cell cycle result from blocking the function of endogenous wild-type PPARgamma. DN-PPARgamma expression enhanced phosphorylation of ERK MAPKs. Furthermore, the ERK specific-inhibitor PD98059 blocked DN-PPARgamma-induced phosphorylation of Rb and expression of cyclin A and MCM7. Our data thus suggest that DN-PPARgamma promotes cell cycle progression and cell growth in CASMCs by modulating fundamental cell cycle regulatory proteins and MAPK mitogenic signaling pathways in vascular smooth muscle cells (VSMCs). PMID- 20300580 TI - Music composition from the brain signal: representing the mental state by music. AB - This paper proposes a method to translate human EEG into music, so as to represent mental state by music. The arousal levels of the brain mental state and music emotion are implicitly used as the bridge between the mind world and the music. The arousal level of the brain is based on the EEG features extracted mainly by wavelet analysis, and the music arousal level is related to the musical parameters such as pitch, tempo, rhythm, and tonality. While composing, some music principles (harmonics and structure) were taken into consideration. With EEGs during various sleep stages as an example, the music generated from them had different patterns of pitch, rhythm, and tonality. 35 volunteers listened to the music pieces, and significant difference in music arousal levels was found. It implied that different mental states may be identified by the corresponding music, and so the music from EEG may be a potential tool for EEG monitoring, biofeedback therapy, and so forth. PMID- 20300581 TI - Modeling Cu(II) binding to peptides using the extensible systematic force field. AB - The utility of the extensible systematic force field (ESFF) was tested for copper(II) binding to a 34-amino-acid Cu(II) peptide, which includes five histidine residues and is the putative copper-binding site of lysyl oxidase. To improve computational efficiency, distance geometry calculations were used to constrain all combinations of three histidine ligands to be within bonding distance of the copper and the best results were utilized as starting structures for the ESFF computations. All likely copper geometries were modeled, but the results showed only a small dependence on the geometrical model in that all resulted in a distorted square pyramidal geometry about the copper, some of the imidazole rings were poorly oriented for ligation to the Cu(II), and the copper nitrogen bond distances were too long. The results suggest that ESFF should be used with caution for Cu(II) complexes where the copper-ligand bonds have significant covalency and when the ligands are not geometrically constrained to be planar. PMID- 20300582 TI - A false case of clozapine-resistant schizophrenia. AB - One of the subjects that most concerns physicians is treatment-resistance. About 30%-60% of schizophrenia patients do not respond adequately to antipsychotic treatment and are known as refractory schizophrenia patients. Clozapine has been the drug of choice in such cases. However, approximately 30% of them do not respond to clozapine either. Here, we describe a patient with an initial diagnosis of refractory schizophrenia who had a history of dramatic aggressiveness. However, in this case, "refractoriness" was a wrong diagnosis. A case of psychosis secondary to epilepsy had been treated as schizophrenia for almost 20 years. Reports like this one are important because they remind us of how a thorough investigation can lead to the correct diagnosis and improve the patient's prognosis. PMID- 20300583 TI - Concordance of KRAS/BRAF Mutation Status in Metastatic Colorectal Cancer before and after Anti-EGFR Therapy. AB - Anti-EGFR targeted therapy is a potent strategy in the treatment of metastatic colorectal cancer (mCRC) but activating mutations in the KRAS gene are associated with poor response to this treatment. Therefore, KRAS mutation analysis is employed in the selection of patients for EGFR-targeted therapy and various studies have shown a high concordance between the mutation status in primary CRC and corresponding metastases. However, although development of therapy related resistance occurs also in the context of novel drugs such as tyrosine kinase inhibitors the effect of the anti-EGFR treatment on the KRAS/BRAF mutation status itself in recurrent mCRC has not yet been clarified. Therefore, we analyzed 21 mCRCs before/after anti-EGFR therapy and found a pre-/posttherapeutic concordance of the KRAS/BRAF mutation status in 20 of the 21 cases examined. In the one discordant case, further analyses revealed that a tumor mosaicism or multiple primary tumors were present, indicating that anti-EGFR therapy has no influence on KRAS/BRAF mutation status in mCRC. Moreover, as the preselection of patients with a KRAS(wt) genotype for anti-EGFR therapy has become a standard procedure, sample sets such ours might be the basis for future studies addressing the identification of potential anti-EGFR therapy induced genetic alterations apart from KRAS/BRAF mutations. PMID- 20300584 TI - Pretreatment with Cry1Ac protoxin modulates the immune response, and increases the survival of Plasmodium-infected CBA/Ca mice. AB - Malaria is a major global health problem that kills 1-2 million people each year. Despite exhaustive research, naturally acquired immunity is poorly understood. Cry1A proteins are potent immunogens with adjuvant properties and are able to induce strong cellular and humoral responses. In fact, it has been shown that administration of Cry1Ac protoxin alone or with amoebic lysates induces protection against the lethal infection caused by the protozoa Naegleria fowleri. In this work, we studied whether Cry1Ac is able to activate the innate immune response to induce protection against Plasmodium berghei ANKA (lethal) and P. chabaudi AS (nonlethal) parasites in CBA/Ca mice. Treatment with Cry1Ac induced protection against both Plasmodium species in terms of reduced parasitaemia, longer survival time, modulation of pro- and anti-inflammatory cytokines, and increased levels of specific antibodies against Plasmodium. Understanding how to boost innate immunity to Plasmodium infection should lead to immunologically based intervention strategies. PMID- 20300585 TI - Myonecrosis in sickle cell anemia-overlooked and underdiagnosed. AB - Medical literature detailing muscular complications of sickle cell anemia is sparse and limited to a few case-reports. Features consistent with myositis and myonecrosis are often overlooked and patients are inadequately treated, leading to unforeseen complications. We report an interesting case of sickle cell myonecrosis and review the existing literature on this subject. PMID- 20300586 TI - Differential expression of microRNAs between eutopic and ectopic endometrium in ovarian endometriosis. AB - Endometriosis, defined as the presence of endometrial tissue outside the uterus, is a common gynecological disease with poorly understood pathogenesis. MicroRNAs are members of a class of small noncoding RNA molecules that have a critical role in posttranscriptional regulation of gene expression by repression of target mRNAs translation. We assessed differentially expressed microRNAs in ectopic endometrium compared with eutopic endometrium in 3 patients through microarray analysis. We identified 50 microRNAs differentially expressed and the differential expression of five microRNAs was validated by real-time RT-PCR in other 13 patients. We identified in silico their predicted targets, several of which match the genes that have been identified to be differentially expressed in ectopic versus eutopic endometrium in studies of gene expression. A functional analysis of the predicted targets indicates that several of these are involved in molecular pathways implicated in endometriosis, thus strengthening the hypothesis of the role of microRNAs in this pathology. PMID- 20300587 TI - Successful treatment of Cisplatin overdose with plasma exchange. AB - Accidental cisplatin overdose has been occurring with an increasing frequency due to expanding usage of the agent. However, the optimal strategy to treat such patients remains to be established. Here, we report a case of large cisplatin overdose, successfully managed by plasma exchange, intravenous hydration, granulocyte colony-stimulating factor (G-CSF) administration, and other supportive care. A 67-year-old man with esophageal carcinoma received a large cisplatin overdose of 240 mg/m(2), when he received adjuvant therapy following subtotal esophagectomy. On day 4, he experienced frank cisplatin toxicities and emergency plasma exchange was initiated. With 7 cycles of plasma exchange, the cisplatin concentration decreased from 2,350 to 110 ng/mL. Severe bone marrow suppression with high fever ensued on day 10, which was successfully treated with G-CSF and antibiotics. Despite moderate hearing sense reduction, he recovered without significant complications. Immediate plasma exchange with hydration and other care was efficacious in quickly lowering cisplatin concentrations. PMID- 20300588 TI - Tomatine adjuvantation of protective immunity to a major pre-erythrocytic vaccine candidate of malaria is mediated via CD8+ T cell release of IFN-gamma. AB - The glycoalkaloid tomatine, derived from the wild tomato, can act as a powerful adjuvant to elicit an antigen-specific cell-mediated immune response to the circumsporozoite (CS) protein, a major pre-erythrocytic stage malaria vaccine candidate antigen. Using a defined MHC-class-I-restricted CS epitope in a Plasmodium berghei rodent model, antigen-specific cytotoxic T lymphocyte activity and IFN-gamma secretion ex vivo were both significantly enhanced compared to responses detected from similarly stimulated splenocytes from naive and tomatine saline-immunized mice. Further, through lymphocyte depletion it is demonstrated that antigen-specific IFN-gamma is produced exclusively by the CD8(+) T cell subset. We conclude that the processing of the P. berghei CS peptide as an exogenous antigen and its presentation via MHC class I molecules to CD8(+) T cells leads to an immune response that is an in vitro correlate of protection against pre-erythrocytic malaria. Further characterization of tomatine as an adjuvant in malaria vaccine development is indicated. PMID- 20300589 TI - Orthotopic Liver Transplantation: Is There a Risk for Listeria monocytogenes Infection? AB - Immunosuppression of any kind is a known risk factor for infection with Listeria monocytogenes (L. monocytogenes). Particularly, patients with impaired liver function are at increased risk of developing an aggravated course of infection with this bacterial pathogen (see Nolla-Salas et al.; 2002 and Cabellos et al.; 2008). It is a well-known pathogen in immunocompromised patients, but has only seldom been reported following orthotopic liver transplantation. Invasion of the central nervous system presenting as meningitis or meningoencephalitis and bacteremia are the principal clinical manifestations of listerial infections (see Brouwer et al.; 2006). We present an account of a case of a patient who developed L. monocytogenes meningitis during the early period after liver transplantation. PMID- 20300590 TI - Size of AT(n) insertions in promoter region modulates Gmhsp17.6-L mRNA transcript levels. AB - During earlier experiments, an SSR molecular marker (176 Soy HSP) showing high correlation (70%) with resistance/susceptibility to javanese root-knot nematode Meloidogyne javanica was identified in soybean. After being sequenced, results indicated that the SSR 176 Soy HSP marker was inserted in the promoter region of Gmhsp17.6-L gene. It was also detected in this region that resistant genotypes presented insertions between AT(31) and AT(33) in size and susceptible genotypes, AT(9). Gmhsp17.6-L gene coding region presented a perfect match in amino acid sequence in all soybean genotypes. A ribonuclease protection assay showed that Gmhsp17.6-L gene mRNA transcripts were present in all genotypes. A real-time relative quantification (qPCR) indicated in the resistant individuals higher mRNA transcripts levels, which presented in the sequencing more AT(n) insertions. These results suggest that the number of AT(n) insertions inside this promoter region could modulate up or down gene levels. Those findings can lead to the possibility of manipulating, between some limits, the mRNA transcripts levels using different sizes of AT(n) insertions. PMID- 20300591 TI - Protective effect and mechanisms of radix astragali injection on the intestinal mucosa of rats with obstructive jaundice. AB - OBJECTIVE: To research the protective effects and mechanisms of Radix Astragali injection on the intestinal mucosa of rats with obstructive jaundice (OJ). METHODS: The rats were randomly divided into sham-operated, model control and Radix Astragali treated group. We observed the pathological changes of intestinal mucosa, expression levels of Bax and NF-kappaB proteins, and apoptosis indexes in intestinal mucosa as well as serum NO, MDA and SOD contents, respectively, on 7d, 14d, 21d and 28d after operation. RESULTS: The pathological severity score (on 7d and 14d), apoptotic indexes (on 14d) of the intestinal mucosa and serum MDA content (on 14d) of treated group were significantly lower than those in the model control group (P < .05). The serum SOD contents (on all time points) of treated group were significantly higher than those in the model control group (P < .05). The sham-operated group (on 21d) of the product of staining intensity and positive rate of Bax protein was significantly lower than model control group (P < .05). CONCLUSION: Radix Astragali injection could protect the intestinal mucosa of OJ rats by increasing the content of SOD, reducing the content of MDA, inhibiting the apoptosis and relieving the pathological changes of intestinal mucosa. PMID- 20300592 TI - Development and validation of a spike detection and classification algorithm aimed at implementation on hardware devices. AB - Neurons cultured in vitro on MicroElectrode Array (MEA) devices connect to each other, forming a network. To study electrophysiological activity and long term plasticity effects, long period recording and spike sorter methods are needed. Therefore, on-line and real time analysis, optimization of memory use and data transmission rate improvement become necessary. We developed an algorithm for amplitude-threshold spikes detection, whose performances were verified with (a) statistical analysis on both simulated and real signal and (b) Big O Notation. Moreover, we developed a PCA-hierarchical classifier, evaluated on simulated and real signal. Finally we proposed a spike detection hardware design on FPGA, whose feasibility was verified in terms of CLBs number, memory occupation and temporal requirements; once realized, it will be able to execute on-line detection and real time waveform analysis, reducing data storage problems. PMID- 20300594 TI - Long-term outcomes following laparoscopic and abdominal supracervical hysterectomies. AB - Long-term outcomes, in terms of cervical stump symptoms and overall patient satisfaction, were studied in women both after abdominal (SAH) and laparosocopic (LSH) supracervical hysterectomies. Altogether, 134 women had SAH and 315 women LSH during 2004 and 2005 at our department. The response rate of this retrospective study was 79%. Persistent vaginal bleeding after the surgery was reported by 17% in the SAH group and 24% in the LSH group. Regular bleeding was reported by only 8% in both study groups, and the women rarely found the bleeding bothersome. The women reported a significant pain reduction after the surgery, but women having a hysterectomy because of pain and/or endometriosis should be informed about the possibility of persistent symptoms. The overall patient satisfaction after both procedures was high, but the patients should have proper preoperative information about the possibility of cervical stump symptoms after any supracervical hysterectomy. PMID- 20300593 TI - Alteration of sarcoplasmic reticulum ca release in skeletal muscle from calpain 3 deficient mice. AB - Mutations of Ca(2+)-activated proteases (calpains) cause muscular dystrophies. Nevertheless, the specific role of calpains in Ca(2+) signalling during the onset of dystrophies remains unclear. We investigated Ca(2+) handling in skeletal cells from calpain 3-deficient mice. [Ca(2+)](i) responses to caffeine, a ryanodine receptor (RyR) agonist, were decreased in -/- myotubes and absent in -/- myoblasts. The -/- myotubes displayed smaller amplitudes of the Ca(2+) transients induced by cyclopiazonic acid in comparison to wild type cells. Inhibition of L type Ca(2+) channels (LCC) suppressed the caffeine-induced [Ca(2+)](i) responses in -/- myotubes. Hence, the absence of calpain 3 modifies the sarcoplasmic reticulum (SR) Ca(2+) release, by a decrease of the SR content, an impairment of RyR signalling, and an increase of LCC activity. We propose that calpain 3 dependent proteolysis plays a role in activating support proteins of intracellular Ca(2+) signalling at a stage of cellular differentiation which is crucial for skeletal muscle regeneration. PMID- 20300595 TI - I-131 treatment of graves' disease in an unsuspected first trimester pregnancy; the potential for adverse effects on the fetus and a review of the current guidelines for pregnancy screening. AB - Graves' disease is a thyroid-specific autoimmune disorder in which the body makes antibodies to the thyroid-stimulating hormone receptor leading to hyperthyroidism. Therapeutic options for the treatment of Graves' disease include medication, radioactive iodine ablation, and surgery. Radioactive iodine is absolutely contraindicated in pregnancy as exposure to I-131 to the fetal thyroid can result in fetal hypothyroidism and cretinism. Here we describe a case of a female patient with recurrent Graves' disease, who inadvertently received I-131 therapy when she was estimated to be eight days pregnant. This was despite the obtaining of a negative history of pregnancy and a negative urine pregnancy test less than 24 hours prior to ablation. At birth, the infant was found to have neonatal Graves' disease. The neonatal Graves' disease resolved spontaneously. It was suspected that the fetal thyroid did not trap any I-131 as it does not concentrate iodine until 10 weeks of gestation. PMID- 20300596 TI - Increased Serum PAI-1 Levels in Subjects with Metabolic Syndrome and Long-Term Adverse Mental Symptoms: A Population-Based Study. AB - Depression is an independent risk factor for cardiovascular diseases and is associated with metabolic syndrome (MetS). Levels of plasminogen activator inhibitor-1 (PAI-1), an inhibitor of tissue-type and urokinase-type plasminogen activators, are associated with MetS. To clarify the role of PAI-1 in subjects with long-term adverse mental symptomatology (LMS; including depression) and MetS, we measured circulating PAI-1 levels in controls (n = 111), in subjects with MetS and free of mental symptoms (n = 42), and in subjects with both MetS and long-term mental symptoms (n = 70). PAI-1 increased linearly across the three groups in men. In logistic regression analysis, men with PAI-1 levels above the median had a 3.4-fold increased likelihood of suffering from the comorbidity of long-term adverse mental symptoms and MetS, while no such associations were detected in women. In conclusion, our results suggest that in men high PAI-1 levels are independently associated with long-term mental symptomatology. PMID- 20300597 TI - Sporadic, nontrauma-related, desmoid tumor of the pancreas: a rare disease-case report and literature review. AB - Desmoid tumors (DTs) are neoplasms of fibroblastic origin characterized by lack of a capsule. They are nonmetastatic and locally aggressive. Intraabdominal DTs are often observed in familial adenomatous polyposis and Gardner syndrome or subsequent to localized traumatic injury. Sporadic forms are defined as nontrauma or nongenetic-related DTs. Isolated, sporadic pancreatic DTs have been considered anecdotal, with only 9 cases described in the literature. We report the case of a 68-year-old man with a case of sporadic cystic DT localized to the pancreatic tail. The tumor was discovered incidentally during computerized tomography performed for an unrelated condition. The patient was asymptomatic; however, biopsy was performed on the clinical suspicion of cystic cancer of the pancreas. Pathology analysis showed fibroblastic proliferation, and the diagnosis of DT was confirmed by immunohistochemical staining for beta-catenin. The patient underwent resection with no further treatment and remain disease-free 60 months after surgery. PMID- 20300598 TI - Size functions for the morphological analysis of melanocytic lesions. AB - Size Functions and Support Vector Machines are used to implement a new automatic classifier of melanocytic lesions. This is mainly based on a qualitative assessment of asymmetry, performed by halving images by several lines through the center of mass, and comparing the two halves in terms of color, mass distribution, and boundary. The program is used, at clinical level, with two thresholds, so that comparison of the two outputs produces a report of low-middle high risk. Experimental results on 977 images, with cross-validation, are reported. PMID- 20300599 TI - Rituximab Efficacy during a Refractory Polyarteritis Nodosa Flare. AB - Polyarteritis nodosa (PAN) is a systemic vasculitis whose severe forms are treated with glucocorticoids and cyclophosphamide. Refractory patients are exposed to many complications, notably accelerated atherosclerosis. We report a case report of 71-year-old man followed for polyarteritis nodosa refractory to glucocorticoids and cyclosphosphamide. Systemic vasculitis relapses are followed to accelerated atherosclerosis: severe ischemic lesions led to amputation of lower limbs. Remission of refractory PAN is obtained with rituximab. Disappearance of biological inflammatory is allowed to regression of ischemic lesions in upper limbs. In this situation, we recommend a systematic vascular work-up for patients suffered from refractory vasculitis. On the other hand, therapeutic trials are needed to determine the real efficacy and place of rituximab in the treatment of polyarteritis nodosa. PMID- 20300600 TI - Innate killing of Leishmania donovani by macrophages of the splenic marginal zone requires IRF-7. AB - Highly phagocytic macrophages line the marginal zone (MZ) of the spleen and the lymph node subcapsular sinus. Although these macrophages have been attributed with a variety of functions, including the uptake and clearance of blood and lymph-borne pathogens, little is known about the effector mechanisms they employ after pathogen uptake. Here, we have combined gene expression profiling and RNAi using a stromal macrophage cell line with in situ analysis of the leishmanicidal activity of marginal zone macrophages (MZM) and marginal metallophilic macrophages (MMM) in wild type and gene targeted mice. Our data demonstrate a critical role for interferon regulatory factor-7 (IRF-7) in regulating the killing of intracellular Leishmania donovani by these specialised splenic macrophage sub-populations. This study, therefore, identifies a new role for IRF 7 as a regulator of innate microbicidal activity against this, and perhaps other, non-viral intracellular pathogens. This study also highlights the importance of selecting appropriate macrophage populations when studying pathogen interactions with this functionally diverse lineage of cells. PMID- 20300601 TI - Membrane damage elicits an immunomodulatory program in Staphylococcus aureus. AB - The Staphylococcus aureus HrtAB system is a hemin-regulated ABC transporter composed of an ATPase (HrtA) and a permease (HrtB) that protect S. aureus against hemin toxicity. S. aureus strains lacking hrtA exhibit liver-specific hyper virulence and upon hemin exposure over-express and secrete immunomodulatory factors that interfere with neutrophil recruitment to the site of infection. It has been proposed that heme accumulation in strains lacking hrtAB is the signal which triggers S. aureus to elaborate this anti-neutrophil response. However, we report here that S. aureus strains expressing catalytically inactive HrtA do not elaborate the same secreted protein profile. This result indicates that the physical absence of HrtA is responsible for the increased expression of immunomodulatory factors, whereas deficiencies in the ATPase activity of HrtA do not contribute to this process. Furthermore, HrtB expression in strains lacking hrtA decreases membrane integrity consistent with dysregulated permease function. Based on these findings, we propose a model whereby hemin-mediated over expression of HrtB in the absence of HrtA damages the staphylococcal membrane through pore formation. In turn, S. aureus senses this membrane damage, triggering the increased expression of immunomodulatory factors. In support of this model, wildtype S. aureus treated with anti-staphylococcal channel-forming peptides produce a secreted protein profile that mimics the effect of treating DeltahrtA with hemin. These results suggest that S. aureus senses membrane damage and elaborates a gene expression program that protects the organism from the innate immune response of the host. PMID- 20300602 TI - YfiBNR mediates cyclic di-GMP dependent small colony variant formation and persistence in Pseudomonas aeruginosa. AB - During long-term cystic fibrosis lung infections, Pseudomonas aeruginosa undergoes genetic adaptation resulting in progressively increased persistence and the generation of adaptive colony morphotypes. This includes small colony variants (SCVs), auto-aggregative, hyper-adherent cells whose appearance correlates with poor lung function and persistence of infection. The SCV morphotype is strongly linked to elevated levels of cyclic-di-GMP, a ubiquitous bacterial second messenger that regulates the transition between motile and sessile, cooperative lifestyles. A genetic screen in PA01 for SCV-related loci identified the yfiBNR operon, encoding a tripartite signaling module that regulates c-di-GMP levels in P. aeruginosa. Subsequent analysis determined that YfiN is a membrane-integral diguanylate cyclase whose activity is tightly controlled by YfiR, a small periplasmic protein, and the OmpA/Pal-like outer membrane lipoprotein YfiB. Exopolysaccharide synthesis was identified as the principal downstream target for YfiBNR, with increased production of Pel and Psl exopolysaccharides responsible for many characteristic SCV behaviors. An yfi dependent SCV was isolated from the sputum of a CF patient. Consequently, the effect of the SCV morphology on persistence of infection was analyzed in vitro and in vivo using the YfiN-mediated SCV as a representative strain. The SCV strain exhibited strong, exopolysaccharide-dependent resistance to nematode scavenging and macrophage phagocytosis. Furthermore, the SCV strain effectively persisted over many weeks in mouse infection models, despite exhibiting a marked fitness disadvantage in vitro. Exposure to sub-inhibitory concentrations of antibiotics significantly decreased both the number of suppressors arising, and the relative fitness disadvantage of the SCV mutant in vitro, suggesting that the SCV persistence phenotype may play a more important role during antimicrobial chemotherapy. This study establishes YfiBNR as an important player in P. aeruginosa persistence, and implicates a central role for c-di-GMP, and by extension the SCV phenotype in chronic infections. PMID- 20300604 TI - N-acetylglucosamine induces white to opaque switching, a mating prerequisite in Candida albicans. AB - To mate, the fungal pathogen Candida albicans must undergo homozygosis at the mating-type locus and then switch from the white to opaque phenotype. Paradoxically, opaque cells were found to be unstable at physiological temperature, suggesting that mating had little chance of occurring in the host, the main niche of C. albicans. Recently, however, it was demonstrated that high levels of CO(2), equivalent to those found in the host gastrointestinal tract and select tissues, induced the white to opaque switch at physiological temperature, providing a possible resolution to the paradox. Here, we demonstrate that a second signal, N-acetylglucosamine (GlcNAc), a monosaccharide produced primarily by gastrointestinal tract bacteria, also serves as a potent inducer of white to opaque switching and functions primarily through the Ras1/cAMP pathway and phosphorylated Wor1, the gene product of the master switch locus. Our results therefore suggest that signals produced by bacterial co-members of the gastrointestinal tract microbiota regulate switching and therefore mating of C. albicans. PMID- 20300603 TI - Dynamic imaging of experimental Leishmania donovani-induced hepatic granulomas detects Kupffer cell-restricted antigen presentation to antigen-specific CD8 T cells. AB - Kupffer cells (KCs) represent the major phagocytic population within the liver and provide an intracellular niche for the survival of a number of important human pathogens. Although KCs have been extensively studied in vitro, little is known of their in vivo response to infection and their capacity to directly interact with antigen-specific CD8(+) T cells. Here, using a combination of approaches including whole mount and thin section confocal microscopy, adoptive cell transfer and intra-vital 2-photon microscopy, we demonstrate that KCs represent the only detectable population of mononuclear phagocytes within granulomas induced by Leishmania donovani infection that are capable of presenting parasite-derived peptide to effector CD8(+) T cells. This restriction of antigen presentation to KCs within the Leishmania granuloma has important implications for the identification of new candidate vaccine antigens and for the design of novel immuno-therapeutic interventions. PMID- 20300605 TI - Structural basis of cell wall cleavage by a staphylococcal autolysin. AB - The major autolysins (Atl) of Staphylococcus epidermidis and S. aureus play an important role in cell separation, and their mutants are also attenuated in virulence. Therefore, autolysins represent a promising target for the development of new types of antibiotics. Here, we report the high-resolution structure of the catalytically active amidase domain AmiE (amidase S. epidermidis) from the major autolysin of S. epidermidis. This is the first protein structure with an amidase like fold from a bacterium with a gram-positive cell wall architecture. AmiE adopts a globular fold, with several alpha-helices surrounding a central beta sheet. Sequence comparison reveals a cluster of conserved amino acids that define a putative binding site with a buried zinc ion. Mutations of key residues in the putative active site result in loss of activity, enabling us to propose a catalytic mechanism. We also identified and synthesized muramyltripeptide, the minimal peptidoglycan fragment that can be used as a substrate by the enzyme. Molecular docking and digestion assays with muramyltripeptide derivatives allow us to identify key determinants of ligand binding. This results in a plausible model of interaction of this ligand not only for AmiE, but also for other PGN hydrolases that share the same fold. As AmiE active-site mutations also show a severe growth defect, our findings provide an excellent platform for the design of specific inhibitors that target staphylococcal cell separation and can thereby prevent growth of this pathogen. PMID- 20300606 TI - Homeostatic interplay between bacterial cell-cell signaling and iron in virulence. AB - Pathogenic bacteria use interconnected multi-layered regulatory networks, such as quorum sensing (QS) networks to sense and respond to environmental cues and external and internal bacterial cell signals, and thereby adapt to and exploit target hosts. Despite the many advances that have been made in understanding QS regulation, little is known regarding how these inputs are integrated and processed in the context of multi-layered QS regulatory networks. Here we report the examination of the Pseudomonas aeruginosa QS 4-hydroxy-2-alkylquinolines (HAQs) MvfR regulatory network and determination of its interaction with the QS acyl-homoserine-lactone (AHL) RhlR network. The aim of this work was to elucidate paradigmatically the complex relationships between multi-layered regulatory QS circuitries, their signaling molecules, and the environmental cues to which they respond. Our findings revealed positive and negative homeostatic regulatory loops that fine-tune the MvfR regulon via a multi-layered dependent homeostatic regulation of the cell-cell signaling molecules PQS and HHQ, and interplay between these molecules and iron. We discovered that the MvfR regulon component PqsE is a key mediator in orchestrating this homeostatic regulation, and in establishing a connection to the QS rhlR system in cooperation with RhlR. Our results show that P. aeruginosa modulates the intensity of its virulence response, at least in part, through this multi-layered interplay. Our findings underscore the importance of the homeostatic interplay that balances competition within and between QS systems via cell-cell signaling molecules and environmental cues in the control of virulence gene expression. Elucidation of the fine-tuning of this complex relationship offers novel insights into the regulation of these systems and may inform strategies designed to limit infections caused by P. aeruginosa and related human pathogens. PMID- 20300607 TI - Staphylococcus aureus RNAIII binds to two distant regions of coa mRNA to arrest translation and promote mRNA degradation. AB - Staphylococcus aureus RNAIII is the intracellular effector of the quorum sensing system that temporally controls a large number of virulence factors including exoproteins and cell-wall-associated proteins. Staphylocoagulase is one major virulence factor, which promotes clotting of human plasma. Like the major cell surface protein A, the expression of staphylocoagulase is strongly repressed by the quorum sensing system at the post-exponential growth phase. Here we used a combination of approaches in vivo and in vitro to analyze the mechanism used by RNAIII to regulate the expression of staphylocoagulase. Our data show that RNAIII represses the synthesis of the protein through a direct binding with the mRNA. Structure mapping shows that two distant regions of RNAIII interact with coa mRNA and that the mRNA harbors a conserved signature as found in other RNAIII-target mRNAs. The resulting complex is composed of an imperfect duplex masking the Shine Dalgarno sequence of coa mRNA and of a loop-loop interaction occurring downstream in the coding region. The imperfect duplex is sufficient to prevent the formation of the ribosomal initiation complex and to repress the expression of a reporter gene in vivo. In addition, the double-strand-specific endoribonuclease III cleaves the two regions of the mRNA bound to RNAIII that may contribute to the degradation of the repressed mRNA. This study validates another direct target of RNAIII that plays a role in virulence. It also illustrates the diversity of RNAIII-mRNA topologies and how these multiple RNAIII-mRNA interactions would mediate virulence regulation. PMID- 20300617 TI - Pandemic dynamics and the breakdown of herd immunity. AB - In this note we discuss the issues involved in attempting to model pandemic dynamics. More specifically, we show how it may be possible to make projections for the ongoing H1N1 pandemic as extrapolated from knowledge of seasonal influenza. We derive first-approximation parameter estimates for the SIR model to describe seasonal influenza, and then explore the implications of the existing classical epidemiological theory for the case of a pandemic virus. In particular, we note the dramatic nonlinear increase in attack rate as a function of the percentage of susceptibles initially present in the population. This has severe consequences for the pandemic, given the general lack of immunity in the global population. PMID- 20300608 TI - Direct TLR2 signaling is critical for NK cell activation and function in response to vaccinia viral infection. AB - Natural killer (NK) cells play an essential role in innate immune control of poxviral infections in vivo. However, the mechanism(s) underlying NK cell activation and function in response to poxviruses remains poorly understood. In a mouse model of infection with vaccinia virus (VV), the most studied member of the poxvirus family, we identified that the Toll-like receptor (TLR) 2-myeloid differentiating factor 88 (MyD88) pathway was critical for the activation of NK cells and the control of VV infection in vivo. We further showed that TLR2 signaling on NK cells, but not on accessory cells such as dendritic cells (DCs), was necessary for NK cell activation and that this intrinsic TLR2-MyD88 signaling pathway was required for NK cell activation and played a critical role in the control of VV infection in vivo. In addition, we showed that the activating receptor NKG2D was also important for efficient NK activation and function, as well as recognition of VV-infected targets. We further demonstrated that VV could directly activate NK cells via TLR2 in the presence of cytokines in vitro and TLR2-MyD88-dependent activation of NK cells by VV was mediated through the phosphatidylinositol 3-kinase (PI3K)-extracellular signal-regulated kinase (ERK) pathway. Taken together, these results represent the first evidence that intrinsic TLR signaling is critical for NK cell activation and function in the control of a viral infection in vivo, indicate that multiple pathways are required for efficient NK cell activation and function in response to VV infection, and may provide important insights into the design of effective strategies to combat poxviral infections. PMID- 20300618 TI - Evolutionary constraints acting on DDX3X protein potentially interferes with Rev mediated nuclear export of HIV-1 RNA. AB - Differential host-pathogen interactions direct viral replication in infected cells. In HIV-1 infected cells, nuclear export of viral RNA transcripts into cellular cytoplasm is governed by interaction of HIV-1 Rev, Exportin-1 (CRM-1) and DDX3X. Knock down of DDX3X has been shown to drastically impair HIV replication. Here we show that evolutionary forces are responsible for demarking previously unidentified critical functionally important residues on the surface of DDX3X. Using computational approaches, we show that these functional residues, depending on their location, are capable of regulating ATPase and RNA helicase functions of DDX3X. The potential of these residues in designing better blockers against HIV-1 replication was also assessed. Also, using stepwise docking simulations, we could identify DDX3X-CRM-1 interface and its critical functional residues. Our data would help explain the role of DDX3X in HIV-1 Rev function with potential to design new intervention strategies against HIV-1 replication. PMID- 20300619 TI - Neurotrophins regulate bone marrow stromal cell IL-6 expression through the MAPK pathway. AB - BACKGROUND: The host's response to infection is characterized by altered levels of neurotrophins and an influx of inflammatory cells to sites of injured tissue. Progenitor cells that give rise to the differentiated cellular mediators of inflammation are derived from bone marrow progenitor cells where their development is regulated, in part, by cues from bone marrow stromal cells (BMSC). As such, alteration of BMSC function in response to elevated systemic mediators has the potential to alter their function in biologically relevant ways, including downstream alteration of cytokine production that influences hematopoietic development. METHODOLOGY/PRINCIPAL FINDINGS: In the current study we investigated BMSC neurotrophin receptor expression by flow cytometric analysis to determine differences in expression as well as potential to respond to NGF or BDNF. Intracellular signaling subsequent to neurotrophin stimulation of BMSC was analyzed by western blot, microarray analysis, confocal microscopy and real-time PCR. Analysis of BMSC Interleukin-6 (IL-6) expression was completed using ELISA and real-time PCR. CONCLUSION: BMSC established from different individuals had distinct expression profiles of the neurotrophin receptors, TrkA, TrkB, TrkC, and p75(NTR). These receptors were functional, demonstrated by an increase in Akt phosphorylation following BMSC exposure to recombinant NGF or BDNF. Neurotrophin stimulation of BMSC resulted in increased IL-6 gene and protein expression which required activation of ERK and p38 MAPK signaling, but was not mediated by the NFkappaB pathway. BMSC response to neurotrophins, including the up-regulation of IL-6, may alter their support of hematopoiesis and regulate the availability of inflammatory cells for migration to sites of injury or infection. As such, these studies are relevant to the growing appreciation of the interplay between neurotropic mediators and the regulation of hematopoiesis. PMID- 20300620 TI - Bile acid-induced arrhythmia is mediated by muscarinic M2 receptors in neonatal rat cardiomyocytes. AB - BACKGROUND: Intrahepatic cholestasis of pregnancy (ICP) is a common disease affecting up to 5% of pregnancies and which can cause fetal arrhythmia and sudden intrauterine death. We previously demonstrated that bile acid taurocholate (TC), which is raised in the bloodstream of ICP, can acutely alter the rate and rhythm of contraction and induce abnormal calcium destabilization in cultured neonatal rat cardiomyocytes (NRCM). Apart from their hepatic functions bile acids are ubiquitous signalling molecules with diverse systemic effects mediated by either the nuclear receptor FXR or by a recently discovered G-protein coupled receptor TGR5. We aim to investigate the mechanism of bile-acid induced arrhythmogenic effects in an in-vitro model of the fetal heart. METHODS AND RESULTS: Levels of bile acid transporters and nuclear receptor FXR were studied by quantitative real time PCR, western blot and immunostaining, which showed low levels of expression. We did not observe functional involvement of the canonical receptors FXR and TGR5. Instead, we found that TC binds to the muscarinic M(2) receptor in NRCM and serves as a partial agonist of this receptor in terms of inhibitory effect on intracellular cAMP and negative chronotropic response. Pharmacological inhibition and siRNA-knockdown of the M(2) receptor completely abolished the negative effect of TC on contraction, calcium transient amplitude and synchronisation in NRCM clusters. CONCLUSION: We conclude that in NRCM the TC-induced arrhythmia is mediated by the partial agonism at the M(2) receptor. This mechanism might serve as a promising new therapeutic target for fetal arrhythmia. PMID- 20300621 TI - DNA methylation as a biomarker for cardiovascular disease risk. AB - BACKGROUND: Elevated serum homocysteine is associated with an increased risk of cardiovascular disease (CVD). This may reflect a reduced systemic remethylation capacity, which would be expected to cause decreased genomic DNA methylation in peripheral blood leukocytes (PBL). METHODOLOGY/PRINCIPAL FINDINGS: We examined the association between prevalence of CVD (myocardial infarction, stroke) and its predisposing conditions (hypertension, diabetes) and PBL global genomic DNA methylation as represented by ALU and Satellite 2 (AS) repetitive element DNA methylation in 286 participants of the Singapore Chinese Health Study, a population-based prospective investigation of 63,257 men and women aged 45-74 years recruited during 1993-1998. Men exhibited significantly higher global DNA methylation [geometric mean (95% confidence interval (CI)): 159 (143, 178)] than women [133 (121, 147)] (P = 0.01). Global DNA methylation was significantly elevated in men with a history of CVD or its predisposing conditions at baseline (P = 0.03) but not in women (P = 0.53). Fifty-two subjects (22 men, 30 women) who were negative for these CVD/predisposing conditions at baseline acquired one or more of these conditions by the time of their follow-up I interviews, which took place on average about 5.8 years post-enrollment. Global DNA methylation levels of the 22 incident cases in men were intermediate (AS, 177) relative to the 56 male subjects who remained free of CVD/predisposing conditions at follow-up (lowest AS, 132) and the 51 male subjects with a diagnosis of CVD or predisposing conditions reported at baseline (highest AS 184) (P for trend = 0.0008) No such association was observed in women (P = 0.91). Baseline body mass index was positively associated with AS in both men and women (P = 0.007). CONCLUSIONS/SIGNIFICANCE: Our findings indicate that elevated, not decreased, PBL DNA methylation is positively associated with prevalence of CVD/predisposing conditions and obesity in Singapore Chinese. PMID- 20300622 TI - Time-dependent c-Myc transactomes mapped by Array-based nuclear run-on reveal transcriptional modules in human B cells. AB - BACKGROUND: The definition of transcriptional networks through measurements of changes in gene expression profiles and mapping of transcription factor binding sites is limited by the moderate overlap between binding and gene expression changes and the inability to directly measure global nuclear transcription (coined "transactome"). METHODOLOGY/PRINCIPAL FINDINGS: We developed a method to measure nascent nuclear gene transcription with an Array-based Nuclear Run-On (ANRO) assay using commercial microarray platforms. This strategy provides the missing component, the transactome, to fully map transcriptional networks. ANRO measurements in an inducible c-Myc expressing human P493-6 B cell model reveals time-dependent waves of transcription, with a transactome early after c-Myc induction that does not persist at a late, steady-state phase, when genes that are regulated by c-Myc and E2F predominate. Gene set matrix analysis further uncovers functionally related groups of genes putatively regulated by waves of transcription factor motifs following Myc induction, starting with AP1 and CREB that are followed by EGR1, NFkB and STAT, and ending with E2F, Myc and ARNT/HIF motifs. CONCLUSIONS/SIGNIFICANCE: By coupling ANRO with previous global mapping of c-Myc binding sites by chromatin immunoprecipitation (ChIP) in P493-6 cells, we define a set of transcriptionally regulated direct c-Myc target genes and pave the way for the use of ANRO to comprehensively map any transcriptional network. PMID- 20300624 TI - Genetic heterogeneity of oesophageal cancer in high-incidence areas of southern and northern China. AB - BACKGROUND AND OBJECTIVE: Oesophageal cancer is one of the most common and deadliest cancers worldwide. Our previous population-based study reported a high prevalence of oesophageal cancer in Chaoshan, Guangdong Province, China. Ancestors of the Chaoshan population migrated from the Taihang Mountain region of north-central China, which is another high-incidence area for oesophageal cancer. The purpose of the present study was to obtain evidence of inherited susceptibility to oesophageal cancer in the Chaoshan population, with reference to the Taihang Mountain population, with the eventual goal of molecular identification of the disease genes. METHODS: We conducted familial correlation, commingling, and complex segregation analyses of 224 families from the Chaoshan population and 403 families from the Taihang population using the FPMM program of S.A.G.E. version 5.3.0. A second analysis focused on specific families having large numbers of affected individuals or early onset of the disease. RESULTS: For the general population, moderate sib-sib correlation was noticed for esophageal cancer. Additionally, brother-brother correlation was even higher. Commingling analyses indicated that a three-component distribution model best accounts for the variation in age of onset of oesophageal cancer, and that a multifactorial model provides the best fit to the general population data. An autosomal dominant mode and a dominant or recessive major gene with polygenic inheritance were found to be the best models of inherited susceptibility to oesophageal cancer in some large families. CONCLUSIONS: The current results provide evidence for inherited susceptibility to oesophageal cancer in certain high-risk groups in China, and support efforts to identify the susceptibility genes. PMID- 20300623 TI - A new statistic to evaluate imputation reliability. AB - BACKGROUND: As the amount of data from genome wide association studies grows dramatically, many interesting scientific questions require imputation to combine or expand datasets. However, there are two situations for which imputation has been problematic: (1) polymorphisms with low minor allele frequency (MAF), and (2) datasets where subjects are genotyped on different platforms. Traditional measures of imputation cannot effectively address these problems. METHODOLOGY/PRINCIPAL FINDINGS: We introduce a new statistic, the imputation quality score (IQS). In order to differentiate between well-imputed and poorly imputed single nucleotide polymorphisms (SNPs), IQS adjusts the concordance between imputed and genotyped SNPs for chance. We first evaluated IQS in relation to minor allele frequency. Using a sample of subjects genotyped on the Illumina 1 M array, we extracted those SNPs that were also on the Illumina 550 K array and imputed them to the full set of the 1 M SNPs. As expected, the average IQS value drops dramatically with a decrease in minor allele frequency, indicating that IQS appropriately adjusts for minor allele frequency. We then evaluated whether IQS can filter poorly-imputed SNPs in situations where cases and controls are genotyped on different platforms. Randomly dividing the data into "cases" and "controls", we extracted the Illumina 550 K SNPs from the cases and imputed the remaining Illumina 1 M SNPs. The initial Q-Q plot for the test of association between cases and controls was grossly distorted (lambda = 1.15) and had 4016 false positives, reflecting imputation error. After filtering out SNPs with IQS<0.9, the Q-Q plot was acceptable and there were no longer false positives. We then evaluated the robustness of IQS computed independently on the two halves of the data. In both European Americans and African Americans the correlation was >0.99 demonstrating that a database of IQS values from common imputations could be used as an effective filter to combine data genotyped on different platforms. CONCLUSIONS/SIGNIFICANCE: IQS effectively differentiates well-imputed and poorly imputed SNPs. It is particularly useful for SNPs with low minor allele frequency and when datasets are genotyped on different platforms. PMID- 20300625 TI - Genetic characterization of the influenza A pandemic (H1N1) 2009 virus isolates from India. AB - BACKGROUND: The Influenza A pandemic H1N1 2009 (H1N1pdm) virus appeared in India in May 2009 and thereafter outbreaks with considerable morbidity and mortality have been reported from many parts of the country. Continuous monitoring of the genetic makeup of the virus is essential to understand its evolution within the country in relation to global diversification and to track the mutations that may affect the behavior of the virus. METHODS: H1N1pdm viruses were isolated from both recovered and fatal cases representing major cities and sequenced. Phylogenetic analyses of six concatenated whole genomes and the hemagglutinin (HA) gene of seven more isolates from May-September 2009 was performed with reference to 685 whole genomes of global isolates available as of November 24, 2009. Molecular characterization of all the 8 segments was carried out for known pathogenic markers. RESULTS: The first isolate of May 2009 belonged to clade 5. Although clade 7 was the dominant H1N1pdm lineage in India, both clades 6 and 7 were found to be co-circulating. The neuraminidase of all the Indian isolates possessed H275, the marker for sensitivity to the neuraminidase inhibitor Oseltamivir. Some of the mutations in HA are at or in the vicinity of antigenic sites and may therefore be of possible antigenic significance. Among these a D222G mutation in the HA receptor binding domain was found in two of the eight Indian isolates obtained from fatal cases. CONCLUSIONS: The majority of the 13 Indian isolates grouped in the globally most widely circulating H1N1pdm clade 7. Further, correlations of the mutations specific to clade 7 Indian isolates to viral fitness and adaptability in the country remains to be understood. The D222G mutation in HA from isolates of fatal cases needs to be studied for pathogenicity. PMID- 20300626 TI - Testing the effect of metabolic rate on DNA variability at the intra-specific level. AB - We tested the metabolic rate hypothesis (whereby rates of mtDNA evolution are postulated to be mediated primarily by mutagenic by-products of respiration) by examining whether mass-specific metabolic rate was correlated with root-to-tip distance on a set of mtDNA trees for the springtail Cryptopygus antarcticus travei from sub-Antarctic Marion Island.Using Bayesian analyses and a novel application of the comparative phylogenetic method, we did not find significant evidence that contemporary metabolic rates directly correlate with mutation rate (i.e., root-to-tip distance) once the underlying phylogeny is taken into account. However, we did find significant evidence that metabolic rate is dependent on the underlying mtDNA tree, or in other words, lineages with related mtDNA also have similar metabolic rates.We anticipate that future analyses which apply this methodology to datasets with longer sequences, more taxa, or greater variability will have more power to detect a significant direct correlation between metabolic rate and mutation rate. We conclude with suggestions for future analyses that would extend the preliminary approach applied here, in particular highlighting ways to tease apart oxidative stress effects from the effects of population size and/or selection coefficients operating on the molecular evolutionary rate. PMID- 20300627 TI - The neural correlates of visuospatial perceptual and oculomotor extrapolation. AB - The human visual system must perform complex visuospatial extrapolations (VSE) across space and time in order to extract shape and form from the retinal projection of a cluttered visual environment characterized by occluded surfaces and moving objects. Even if we exclude the temporal dimension, for instance when judging whether an extended finger is pointing towards one object or another, the mechanisms of VSE remain opaque. Here we investigated the neural correlates of VSE using functional magnetic resonance imaging in sixteen human observers while they judged the relative position of, or saccaded to, a (virtual) target defined by the extrapolated path of a pointer. Using whole brain and region of interest (ROI) analyses, we compared the brain activity evoked by these VSE tasks to similar control judgements or eye movements made to explicit (dot) targets that did not require extrapolation. The data show that activity in an occipitotemporal region that included the lateral occipital cortex (LOC) was significantly greater during VSE than during control tasks. A similar, though less pronounced, pattern was also evident in regions of the fronto-parietal cortex that included the frontal eye fields. However, none of the ROIs examined exhibited a significant interaction between target type (extrapolated/explicit) and response type (oculomotor/perceptual). These findings are consistent with a close association between visuoperceptual and oculomotor responses, and highlight a critical role for the LOC in the process of VSE. PMID- 20300628 TI - Anti transglutaminase antibodies cause ataxia in mice. AB - BACKGROUND: Celiac disease (CD) is an autoimmune gastrointestinal disorder characterized by the presence of anti-transglutaminase 2 (TG2) and anti-gliadin antibodies. Amongst the neurological dysfunctions associated with CD, ataxia represents the most common one. METHODS: We analyzed by immunohistochemistry, the anti-neural reactivity of the serum from 20 CD patients. To determine the role of anti-TG2 antibodies in ataxia, two anti-TG2 single chain variable fragments (scFv), isolated from a phage-display IgA antibody library, were characterized by immunohistochemistry and ELISA, and injected in mice to study their effects on motor coordination. We found that 75% of the CD patient population without evidence of neurological involvement, has circulating anti-neural IgA and/or IgG antibodies. Two anti-TG2 scFvs, cloned from one CD patient, stained blood vessels but only one reacted with neurons. This anti-TG2 antibody showed cross reactivity with the transglutaminase isozymes TG3 and TG6. Intraventricular injection of the anti-TG2 or the anti-TG2/3/6 cross-reactive scFv provoked transient, equally intensive ataxia in mice. CONCLUSION: The serum from CD patients contains anti TG2, TG3 and TG6 antibodies that may potentially cause ataxia. PMID- 20300629 TI - Influence of maternal gestational treatment with mycobacterial antigens on postnatal immunity in an experimental murine model. AB - BACKGROUND: It has been proposed that the immune system could be primed as early as during the fetal life and this might have an impact on postnatal vaccination. Therefore, we addressed in murine models whether gestational treatment with mycobacterial antigens could induce better immune responses in the postnatal life. METHODS/FINDINGS: BALB/c mice were treated subcutaneously (s.c.) at the second week of gestation with antigen (Ag)85A or heparin-binding hemagglutinin (HBHA) in the absence of adjuvant. Following birth, offspring mice were immunized intranasally (i.n.) with the same antigens formulated with the adjuvant cholera toxin (CT) at week 1 and week 4. One week after the last immunization, we assessed antigen-specific recall interferon gamma (IFN-gamma) responses by in vitro restimulation of lung-derived lymphocytes. Protection against infection was assessed by challenge with high dose Mycobacterium bovis Bacille Calmette-Guerin (BCG) given i.n. We found that recall IFN-gamma responses were higher in the offspring born to the treated mother compared to the untreated-mother. More importantly, we observed that the offspring born to the treated mother controlled infection better than the offspring born to the untreated mother. Since the gestational treatment was done in absence of adjuvant, essentially there was no antibody production observed in the pregnant mice and therefore no influence of maternal antibodies was expected. We hypothesized that the effect of maternal treatment with antigen on the offspring occurred due to antigen transportation through placenta. To trace the antigens, we conjugated fluorescent nanocrystals with Ag85A (Qdot-ITK-Ag85A). After inoculation in the pregnant mice, Qdot-ITK Ag85A conjugates were detected in the liver, spleen of pregnant females and in all the fetuses and placentas examined. CONCLUSION: The fetal immune system could be primed in utero by mycobacterial antigens transported through the placenta. PMID- 20300630 TI - Levels of 17beta-estradiol receptors expressed in embryonic and adult zebrafish following in vivo treatment of natural or synthetic ligands. AB - The nuclear receptors encompass a group of regulatory proteins involved in a number of physiological processes. The estrogen receptors (ERs), of which one alpha and one beta form exist in mammals function as transcription factors in response to 17beta-estradiol (E2). In zebrafish there are three gene products of estrogen receptors and they are denoted esr1 (ERalpha), esr2a (ERbeta2) and esr2b (ERbeta1). Total RNA of zebrafish early life stages (<3, 6, 12, 24, 48, 72, 96 and 120 hours post fertilization) and of adult fish (liver, intestine, eye, heart, brain, ovary, testis, gill, swim bladder and kidney) were isolated following in vivo exposures. Using specific primers for each of the three zebrafish ERs the expression levels were quantified using real time PCR methodology. It was shown that in absence of exposure all three estrogen receptors were expressed in adult fish. The levels of expression of two of these three ER genes, the esr1 and esr2a were altered in organs such as liver, intestine, brain and testis in response to ligand (E2, diethylstilbestrol or 4 nonylphenol). During embryogenesis two of the three receptor genes, esr1 and esr2b were expressed, and in presence of ligand the mRNA levels of these two genes increased. The conclusions are i) estrogen receptor genes are expressed during early development ii) altered expression of esr genes in response to ligand is dependent on the cellular context; iii) the estrogenic ligand 4 nonylphenol, a manufactured compound commonly found in sewage of water treatment plants, acts as an agonist of the estrogen receptor during development and has both agonist and antagonist properties in tissues of adult fish. This knowledge of esr gene function in development and in adult life will help to understand mechanisms of interfering mimicking endocrine chemicals in vivo. PMID- 20300632 TI - Conversion of phase information into a spike-count code by bursting neurons. AB - Single neurons in the cerebral cortex are immersed in a fluctuating electric field, the local field potential (LFP), which mainly originates from synchronous synaptic input into the local neural neighborhood. As shown by recent studies in visual and auditory cortices, the angular phase of the LFP at the time of spike generation adds significant extra information about the external world, beyond the one contained in the firing rate alone. However, no biologically plausible mechanism has yet been suggested that allows downstream neurons to infer the phase of the LFP at the soma of their pre-synaptic afferents. Therefore, so far there is no evidence that the nervous system can process phase information. Here we study a model of a bursting pyramidal neuron, driven by a time-dependent stimulus. We show that the number of spikes per burst varies systematically with the phase of the fluctuating input at the time of burst onset. The mapping between input phase and number of spikes per burst is a robust response feature for a broad range of stimulus statistics. Our results suggest that cortical bursting neurons could play a crucial role in translating LFP phase information into an easily decodable spike count code. PMID- 20300631 TI - A cluster randomized trial of routine HIV-1 viral load monitoring in Zambia: study design, implementation, and baseline cohort characteristics. AB - BACKGROUND: The benefit of routine HIV-1 viral load (VL) monitoring of patients on antiretroviral therapy (ART) in resource-constrained settings is uncertain because of the high costs associated with the test and the limited treatment options. We designed a cluster randomized controlled trial to compare the use of routine VL testing at ART-initiation and at 3, 6, 12, and 18 months, versus our local standard of care (which uses immunological and clinical criteria to diagnose treatment failure, with discretionary VL testing when the two do not agree). METHODOLOGY: Dedicated study personnel were integrated into public-sector ART clinics. We collected participant information in a dedicated research database. Twelve ART clinics in Lusaka, Zambia constituted the units of randomization. Study clinics were stratified into pairs according to matching criteria (historical mortality rate, size, and duration of operation) to limit the effect of clustering, and independently randomized to the intervention and control arms. The study was powered to detect a 36% reduction in mortality at 18 months. PRINCIPAL FINDINGS: From December 2006 to May 2008, we completed enrollment of 1973 participants. Measured baseline characteristics did not differ significantly between the study arms. Enrollment was staggered by clinic pair and truncated at two matched sites. CONCLUSIONS: A large clinical trial of routing VL monitoring was successfully implemented in a dynamic and rapidly growing national ART program. Close collaboration with local health authorities and adequate reserve staff were critical to success. Randomized controlled trials such as this will likely prove valuable in determining long-term outcomes in resource constrained settings. TRIAL REGISTRATION: Clinicaltrials.gov NCT00929604. PMID- 20300633 TI - Cross-presentation of a spread-defective MCMV is sufficient to prime the majority of virus-specific CD8+ T cells. AB - CD8+ T cells can be primed by peptides derived from endogenous proteins (direct presentation), or exogenously acquired protein (cross-presentation). However, the relative ability of these two pathways to prime CD8+ T cells during a viral infection remains controversial. Cytomegaloviruses (CMVs) can infect professional antigen presenting cells (APCs), including dendritic cells, thus providing peptides for direct presentation. However, the viral immune evasion genes profoundly impair recognition of infected cells by CD8+ T cells. Nevertheless, CMV infection elicits a very strong CD8+ T cell response, prompting its recent use as a vaccine vector. We have shown previously that deleting the immune evasion genes from murine cytomegalovirus (MCMV) that target class I MHC presentation, has no impact on the size or breadth of the CD8+ T cell response elicited by infection, suggesting that the majority of MCMV-specific CD8+ T cells in vivo are not directly primed by infected professional APCs. Here we use a novel spread-defective mutant of MCMV, lacking the essential glycoprotein gL, to show that cross-presentation alone can account for the majority of MCMV-specific CD8+ T cell responses to the virus. Our data support the conclusion that cross presentation is the primary mode of antigen presentation by which CD8+ T cells are primed during MCMV infection. PMID- 20300634 TI - Gene expression profile for predicting survival in advanced-stage serous ovarian cancer across two independent datasets. AB - BACKGROUND: Advanced-stage ovarian cancer patients are generally treated with platinum/taxane-based chemotherapy after primary debulking surgery. However, there is a wide range of outcomes for individual patients. Therefore, the clinicopathological factors alone are insufficient for predicting prognosis. Our aim is to identify a progression-free survival (PFS)-related molecular profile for predicting survival of patients with advanced-stage serous ovarian cancer. METHODOLOGY/PRINCIPAL FINDINGS: Advanced-stage serous ovarian cancer tissues from 110 Japanese patients who underwent primary surgery and platinum/taxane-based chemotherapy were profiled using oligonucleotide microarrays. We selected 88 PFS related genes by a univariate Cox model (p<0.01) and generated the prognostic index based on 88 PFS-related genes after adjustment of regression coefficients of the respective genes by ridge regression Cox model using 10-fold cross validation. The prognostic index was independently associated with PFS time compared to other clinical factors in multivariate analysis [hazard ratio (HR), 3.72; 95% confidence interval (CI), 2.66-5.43; p<0.0001]. In an external dataset, multivariate analysis revealed that this prognostic index was significantly correlated with PFS time (HR, 1.54; 95% CI, 1.20-1.98; p = 0.0008). Furthermore, the correlation between the prognostic index and overall survival time was confirmed in the two independent external datasets (log rank test, p = 0.0010 and 0.0008). CONCLUSIONS/SIGNIFICANCE: The prognostic ability of our index based on the 88-gene expression profile in ridge regression Cox hazard model was shown to be independent of other clinical factors in predicting cancer prognosis across two distinct datasets. Further study will be necessary to improve predictive accuracy of the prognostic index toward clinical application for evaluation of the risk of recurrence in patients with advanced-stage serous ovarian cancer. PMID- 20300635 TI - Cerebral asymmetries: complementary and independent processes. AB - Most people are right-handed and left-cerebrally dominant for speech, leading historically to the general notion of left-hemispheric dominance, and more recently to genetic models proposing a single lateralizing gene. This hypothetical gene can account for higher incidence of right-handers in those with left cerebral dominance for speech. It remains unclear how this dominance relates to the right-cerebral dominance for some nonverbal functions such as spatial or emotional processing. Here we use functional magnetic resonance imaging with a sample of 155 subjects to measure asymmetrical activation induced by speech production in the frontal lobes, by face processing in the temporal lobes, and by spatial processing in the parietal lobes. Left-frontal, right-temporal, and right parietal dominance were all intercorrelated, suggesting that right-cerebral biases may be at least in part complementary to the left-hemispheric dominance for language. However, handedness and parietal asymmetry for spatial processing were uncorrelated, implying independent lateralizing processes, one producing a leftward bias most closely associated with handedness, and the other a rightward bias most closely associated with spatial attention. PMID- 20300636 TI - Serum amyloid P therapeutically attenuates murine bleomycin-induced pulmonary fibrosis via its effects on macrophages. AB - Macrophages promote tissue remodeling but few mechanisms exist to modulate their activity during tissue fibrosis. Serum amyloid P (SAP), a member of the pentraxin family of proteins, signals through Fcgamma receptors which are known to affect macrophage activation. We determined that IPF/UIP patients have increased protein levels of several alternatively activated pro-fibrotic (M2) macrophage-associated proteins in the lung and monocytes from these patients show skewing towards an M2 macrophage phenotype. SAP therapeutically inhibits established bleomycin-induced pulmonary fibrosis, when administered systemically or locally to the lungs. The reduction in aberrant collagen deposition was associated with a reduction in M2 macrophages in the lung and increased IP10/CXCL10. These data highlight the role of macrophages in fibrotic lung disease, and demonstrate a therapeutic action of SAP on macrophages which may extend to many fibrotic indications caused by over exuberant pro-fibrotic macrophage responses. PMID- 20300637 TI - Source partitioning using stable isotopes: coping with too much variation. AB - BACKGROUND: Stable isotope analysis is increasingly being utilised across broad areas of ecology and biology. Key to much of this work is the use of mixing models to estimate the proportion of sources contributing to a mixture such as in diet estimation. METHODOLOGY: By accurately reflecting natural variation and uncertainty to generate robust probability estimates of source proportions, the application of Bayesian methods to stable isotope mixing models promises to enable researchers to address an array of new questions, and approach current questions with greater insight and honesty. CONCLUSIONS: We outline a framework that builds on recently published Bayesian isotopic mixing models and present a new open source R package, SIAR. The formulation in R will allow for continued and rapid development of this core model into an all-encompassing single analysis suite for stable isotope research. PMID- 20300638 TI - Platelet-mediated metabolism of the common dietary flavonoid, quercetin. AB - BACKGROUND: Flavonoid metabolites remain in blood for periods of time potentially long enough to allow interactions with cellular components of this tissue. It is well-established that flavonoids are metabolised within the intestine and liver into methylated, sulphated and glucuronidated counterparts, which inhibit platelet function. METHODOLOGY/PRINCIPAL FINDINGS: We demonstrate evidence suggesting platelets which contain metabolic enzymes, as an alternative location for flavonoid metabolism. Quercetin and a plasma metabolite of this compound, 4' O-methyl quercetin (tamarixetin) were shown to gain access to the cytosolic compartment of platelets, using confocal microscopy. High performance liquid chromatography (HPLC) and mass spectrometry (MS) showed that quercetin was transformed into a compound with a mass identical to tamarixetin, suggesting that the flavonoid was methylated by catechol-O-methyl transferase (COMT) within platelets. CONCLUSIONS/SIGNIFICANCE: Platelets potentially mediate a third phase of flavonoid metabolism, which may impact on the regulation of the function of these cells by metabolites of these dietary compounds. PMID- 20300639 TI - Long-term mortality in patients diagnosed with meningococcal disease: a Danish nationwide cohort study. AB - BACKGROUND: In contrast to the case fatality rate of patients diagnosed with meningococcal disease (MD) the long-term mortality in these patients is poorly documented. METHODOLOGY/PRINCIPAL FINDINGS: We performed a nationwide, population based cohort study including all Danish patients diagnosed with MD from 1977 through 2006 and alive one year after diagnosis. Data was retrieved from the Danish National Hospital Register, the Danish Civil Registration System and the Danish Register of Causes of Death. For each patient four age- and gender-matched individuals were identified from the population cohort. The siblings of the MD patients and of the individuals from the population cohort were identified. We constructed Kaplan-Meier survival curves and used Cox regression analysis, cumulative incidence function and subdistribution hazard regression to estimate mortality rate ratios (MRR) and analyze causes of death. We identified 4,909 MD patients, 19,636 individuals from the population cohort, 8,126 siblings of MD patients and 31,140 siblings of the individuals from the population cohort. The overall MRR for MD patients was 1.27 (95% confidence interval (CI), 1.12-1.45), adjusted MRR, 1.21 (95% CI, 1.06-1.37). MD was associated with increased risk of death due to nervous system diseases (MRR 3.57 (95% CI, 1.82-7.00). No increased mortality due to infections, neoplasms or cardiovascular diseases was observed. The MRR for siblings of MD patients compared with siblings of the individuals from the population cohort was 1.17 (95% CI, 0.92-1.48). CONCLUSIONS: Patients surviving the acute phase of MD have increased long-term mortality, but the excess risk of death is small and stems mainly from nervous system diseases. PMID- 20300640 TI - Deciphering normal blood gene expression variation--The NOWAC postgenome study. AB - There is growing evidence that gene expression profiling of peripheral blood cells is a valuable tool for assessing gene signatures related to exposure, drug response, or disease. However, the true promise of this approach can not be estimated until the scientific community has robust baseline data describing variation in gene expression patterns in normal individuals. Using a large representative sample set of postmenopausal women (N = 286) in the Norwegian Women and Cancer (NOWAC) postgenome study, we investigated variability of whole blood gene expression in the general population. In particular, we examined changes in blood gene expression caused by technical variability, normal inter individual differences, and exposure variables at proportions and levels relevant to real-life situations. We observe that the overall changes in gene expression are subtle, implying the need for careful analytic approaches of the data. In particular, technical variability may not be ignored and subsequent adjustments must be considered in any analysis. Many new candidate genes were identified that are differentially expressed according to inter-individual (i.e. fasting, BMI) and exposure (i.e. smoking) factors, thus establishing that these effects are mirrored in blood. By focusing on the biological implications instead of directly comparing gene lists from several related studies in the literature, our analytic approach was able to identify significant similarities and effects consistent across these reports. This establishes the feasibility of blood gene expression profiling, if they are predicated upon careful experimental design and analysis in order to minimize confounding signals, artifacts of sample preparation and processing, and inter-individual differences. PMID- 20300641 TI - Fatal cardiac arrhythmia and long-QT syndrome in a new form of congenital generalized lipodystrophy with muscle rippling (CGL4) due to PTRF-CAVIN mutations. AB - We investigated eight families with a novel subtype of congenital generalized lipodystrophy (CGL4) of whom five members had died from sudden cardiac death during their teenage years. ECG studies revealed features of long-QT syndrome, bradycardia, as well as supraventricular and ventricular tachycardias. Further symptoms comprised myopathy with muscle rippling, skeletal as well as smooth muscle hypertrophy, leading to impaired gastrointestinal motility and hypertrophic pyloric stenosis in some children. Additionally, we found impaired bone formation with osteopenia, osteoporosis, and atlanto-axial instability. Homozygosity mapping located the gene within 2 Mbp on chromosome 17. Prioritization of 74 candidate genes with GeneDistiller for high expression in muscle and adipocytes suggested PTRF-CAVIN (Polymerase I and transcript release factor/Cavin) as the most probable candidate leading to the detection of homozygous mutations (c.160delG, c.362dupT). PTRF-CAVIN is essential for caveolae biogenesis. These cholesterol-rich plasmalemmal vesicles are involved in signal transduction and vesicular trafficking and reside primarily on adipocytes, myocytes, and osteoblasts. Absence of PTRF-CAVIN did not influence abundance of its binding partner caveolin-1 and caveolin-3. In patient fibroblasts, however, caveolin-1 failed to localize toward the cell surface and electron microscopy revealed reduction of caveolae to less than 3%. Transfection of full-length PTRF CAVIN reestablished the presence of caveolae. The loss of caveolae was confirmed by Atomic Force Microscopy (AFM) in combination with fluorescent imaging. PTRF CAVIN deficiency thus presents the phenotypic spectrum caused by a quintessential lack of functional caveolae. PMID- 20300642 TI - Effects of transcriptional pausing on gene expression dynamics. AB - Stochasticity in gene expression affects many cellular processes and is a source of phenotypic diversity between genetically identical individuals. Events in elongation, particularly RNA polymerase pausing, are a source of this noise. Since the rate and duration of pausing are sequence-dependent, this regulatory mechanism of transcriptional dynamics is evolvable. The dependency of pause propensity on regulatory molecules makes pausing a response mechanism to external stress. Using a delayed stochastic model of bacterial transcription at the single nucleotide level that includes the promoter open complex formation, pausing, arrest, misincorporation and editing, pyrophosphorolysis, and premature termination, we investigate how RNA polymerase pausing affects a gene's transcriptional dynamics and gene networks. We show that pauses' duration and rate of occurrence affect the bursting in RNA production, transcriptional and translational noise, and the transient to reach mean RNA and protein levels. In a genetic repressilator, increasing the pausing rate and the duration of pausing events increases the period length but does not affect the robustness of the periodicity. We conclude that RNA polymerase pausing might be an important evolvable feature of genetic networks. PMID- 20300643 TI - Identification of the regulatory logic controlling Salmonella pathoadaptation by the SsrA-SsrB two-component system. AB - Sequence data from the past decade has laid bare the significance of horizontal gene transfer in creating genetic diversity in the bacterial world. Regulatory evolution, in which non-coding DNA is mutated to create new regulatory nodes, also contributes to this diversity to allow niche adaptation and the evolution of pathogenesis. To survive in the host environment, Salmonella enterica uses a type III secretion system and effector proteins, which are activated by the SsrA-SsrB two-component system in response to the host environment. To better understand the phenomenon of regulatory evolution in S. enterica, we defined the SsrB regulon and asked how this transcription factor interacts with the cis-regulatory region of target genes. Using ChIP-on-chip, cDNA hybridization, and comparative genomics analyses, we describe the SsrB-dependent regulon of ancestral and horizontally acquired genes. Further, we used a genetic screen and computational analyses integrating experimental data from S. enterica and sequence data from an orthologous regulatory system in the insect endosymbiont, Sodalis glossinidius, to identify the conserved yet flexible palindrome sequence that defines DNA recognition by SsrB. Mutational analysis of a representative promoter validated this palindrome as the minimal architecture needed for regulatory input by SsrB. These data provide a high-resolution map of a regulatory network and the underlying logic enabling pathogen adaptation to a host. PMID- 20300644 TI - Detailed simulations of cell biology with Smoldyn 2.1. AB - Most cellular processes depend on intracellular locations and random collisions of individual protein molecules. To model these processes, we developed algorithms to simulate the diffusion, membrane interactions, and reactions of individual molecules, and implemented these in the Smoldyn program. Compared to the popular MCell and ChemCell simulators, we found that Smoldyn was in many cases more accurate, more computationally efficient, and easier to use. Using Smoldyn, we modeled pheromone response system signaling among yeast cells of opposite mating type. This model showed that secreted Bar1 protease might help a cell identify the fittest mating partner by sharpening the pheromone concentration gradient. This model involved about 200,000 protein molecules, about 7000 cubic microns of volume, and about 75 minutes of simulated time; it took about 10 hours to run. Over the next several years, as faster computers become available, Smoldyn will allow researchers to model and explore systems the size of entire bacterial and smaller eukaryotic cells. PMID- 20300645 TI - A multiscale model to investigate circadian rhythmicity of pacemaker neurons in the suprachiasmatic nucleus. AB - The suprachiasmatic nucleus (SCN) of the hypothalamus is a multicellular system that drives daily rhythms in mammalian behavior and physiology. Although the gene regulatory network that produces daily oscillations within individual neurons is well characterized, less is known about the electrophysiology of the SCN cells and how firing rate correlates with circadian gene expression. We developed a firing rate code model to incorporate known electrophysiological properties of SCN pacemaker cells, including circadian dependent changes in membrane voltage and ion conductances. Calcium dynamics were included in the model as the putative link between electrical firing and gene expression. Individual ion currents exhibited oscillatory patterns matching experimental data both in current levels and phase relationships. VIP and GABA neurotransmitters, which encode synaptic signals across the SCN, were found to play critical roles in daily oscillations of membrane excitability and gene expression. Blocking various mechanisms of intracellular calcium accumulation by simulated pharmacological agents (nimodipine, IP3- and ryanodine-blockers) reproduced experimentally observed trends in firing rate dynamics and core-clock gene transcription. The intracellular calcium concentration was shown to regulate diverse circadian processes such as firing frequency, gene expression and system periodicity. The model predicted a direct relationship between firing frequency and gene expression amplitudes, demonstrated the importance of intracellular pathways for single cell behavior and provided a novel multiscale framework which captured characteristics of the SCN at both the electrophysiological and gene regulatory levels. PMID- 20300646 TI - Transcriptome profiling of a toxic dinoflagellate reveals a gene-rich protist and a potential impact on gene expression due to bacterial presence. AB - BACKGROUND: Dinoflagellates are unicellular, often photosynthetic protists that play a major role in the dynamics of the Earth's oceans and climate. Sequencing of dinoflagellate nuclear DNA is thwarted by their massive genome sizes that are often several times that in humans. However, modern transcriptomic methods offer promising approaches to tackle this challenging system. Here, we used massively parallel signature sequencing (MPSS) to understand global transcriptional regulation patterns in Alexandrium tamarense cultures that were grown under four different conditions. METHODOLOGY/PRINCIPAL FINDINGS: We generated more than 40,000 unique short expression signatures gathered from the four conditions. Of these, about 11,000 signatures did not display detectable differential expression patterns. At a p-value < 1E-10, 1,124 signatures were differentially expressed in the three treatments, xenic, nitrogen-limited, and phosphorus-limited, compared to the nutrient-replete control, with the presence of bacteria explaining the largest set of these differentially expressed signatures. CONCLUSIONS/SIGNIFICANCE: Among microbial eukaryotes, dinoflagellates contain the largest number of genes in their nuclear genomes. These genes occur in complex families, many of which have evolved via recent gene duplication events. Our expression data suggest that about 73% of the Alexandrium transcriptome shows no significant change in gene expression under the experimental conditions used here and may comprise a "core" component for this species. We report a fundamental shift in expression patterns in response to the presence of bacteria, highlighting the impact of biotic interaction on gene expression in dinoflagellates. PMID- 20300647 TI - Modeling co-expression across species for complex traits: insights to the difference of human and mouse embryonic stem cells. AB - Complex interactions between genes or proteins contribute substantially to phenotypic evolution. We present a probabilistic model and a maximum likelihood approach for cross-species clustering analysis and for identification of conserved as well as species-specific co-expression modules. This model enables a "soft" cross-species clustering (SCSC) approach by encouraging but not enforcing orthologous genes to be grouped into the same cluster. SCSC is therefore robust to obscure orthologous relationships and can reflect different functional roles of orthologous genes in different species. We generated a time-course gene expression dataset for differentiating mouse embryonic stem (ES) cells, and compiled a dataset of published gene expression data on differentiating human ES cells. Applying SCSC to analyze these datasets, we identified conserved and species-specific gene regulatory modules. Together with protein-DNA binding data, an SCSC cluster specifically induced in murine ES cells indicated that the KLF2/4/5 transcription factors, although critical to maintaining the pluripotent phenotype in mouse ES cells, were decoupled from the OCT4/SOX2/NANOG regulatory module in human ES cells. Two of the target genes of murine KLF2/4/5, LIN28 and NODAL, were rewired to be targets of OCT4/SOX2/NANOG in human ES cells. Moreover, by mapping SCSC clusters onto KEGG signaling pathways, we identified the signal transduction components that were induced in pluripotent ES cells in either a conserved or a species-specific manner. These results suggest that the pluripotent cell identity can be established and maintained through more than one gene regulatory network. PMID- 20300648 TI - Slower visuomotor corrections with unchanged latency are consistent with optimal adaptation to increased endogenous noise in the elderly. AB - We analyzed age-related changes in motor response in a visuomotor compensatory tracking task. Subjects used a manipulandum to attempt to keep a displayed cursor at the center of a screen despite random perturbations to its location. Cross correlation analysis of the perturbation and the subject response showed no age related increase in latency until the onset of response to the perturbation, but substantial slowing of the response itself. Results are consistent with age related deterioration in the ratio of signal to noise in visuomotor response. The task is such that it is tractable to use Bayesian and quadratic optimality assumptions to construct a model for behavior. This model assumes that behavior resembles an optimal controller subject to noise, and parametrizes response in terms of latency, willingness to expend effort, noise intensity, and noise bandwidth. The model is consistent with the data for all young (n = 12, age 20 30) and most elderly (n = 12, age 65-92) subjects. The model reproduces the latency result from the cross-correlation method. When presented with increased noise, the computational model reproduces the experimentally observed age-related slowing and the observed lack of increased latency. The model provides a precise way to quantitatively formulate the long-standing hypothesis that age-related slowing is an adaptation to increased noise. PMID- 20300649 TI - Comparing families of dynamic causal models. AB - Mathematical models of scientific data can be formally compared using Bayesian model evidence. Previous applications in the biological sciences have mainly focussed on model selection in which one first selects the model with the highest evidence and then makes inferences based on the parameters of that model. This "best model" approach is very useful but can become brittle if there are a large number of models to compare, and if different subjects use different models. To overcome this shortcoming we propose the combination of two further approaches: (i) family level inference and (ii) Bayesian model averaging within families. Family level inference removes uncertainty about aspects of model structure other than the characteristic of interest. For example: What are the inputs to the system? Is processing serial or parallel? Is it linear or nonlinear? Is it mediated by a single, crucial connection? We apply Bayesian model averaging within families to provide inferences about parameters that are independent of further assumptions about model structure. We illustrate the methods using Dynamic Causal Models of brain imaging data. PMID- 20300650 TI - Interplay between pleiotropy and secondary selection determines rise and fall of mutators in stress response. AB - Mutators are clones whose mutation rate is about two to three orders of magnitude higher than the rate of wild-type clones and their roles in adaptive evolution of asexual populations have been controversial. Here we address this problem by using an ab initio microscopic model of living cells, which combines population genetics with a physically realistic presentation of protein stability and protein-protein interactions. The genome of model organisms encodes replication controlling genes (RCGs) and genes modeling the mismatch repair (MMR) complexes. The genotype-phenotype relationship posits that the replication rate of an organism is proportional to protein copy numbers of RCGs in their functional form and there is a production cost penalty for protein overexpression. The mutation rate depends linearly on the concentration of homodimers of MMR proteins. By simulating multiple runs of evolution of populations under various environmental stresses--stationary phase, starvation or temperature-jump--we find that adaptation most often occurs through transient fixation of a mutator phenotype, regardless of the nature of stress. By contrast, the fixation mechanism does depend on the nature of stress. In temperature jump stress, mutators take over the population due to loss of stability of MMR complexes. In contrast, in starvation and stationary phase stresses, a small number of mutators are supplied to the population via epigenetic stochastic noise in production of MMR proteins (a pleiotropic effect), and their net supply is higher due to reduced genetic drift in slowly growing populations under stressful environments. Subsequently, mutators in stationary phase or starvation hitchhike to fixation with a beneficial mutation in the RCGs, (second order selection) and finally a mutation stabilizing the MMR complex arrives, returning the population to a non-mutator phenotype. Our results provide microscopic insights into the rise and fall of mutators in adapting finite asexual populations. PMID- 20300651 TI - Neocortical axon arbors trade-off material and conduction delay conservation. AB - The brain contains a complex network of axons rapidly communicating information between billions of synaptically connected neurons. The morphology of individual axons, therefore, defines the course of information flow within the brain. More than a century ago, Ramon y Cajal proposed that conservation laws to save material (wire) length and limit conduction delay regulate the design of individual axon arbors in cerebral cortex. Yet the spatial and temporal communication costs of single neocortical axons remain undefined. Here, using reconstructions of in vivo labelled excitatory spiny cell and inhibitory basket cell intracortical axons combined with a variety of graph optimization algorithms, we empirically investigated Cajal's conservation laws in cerebral cortex for whole three-dimensional (3D) axon arbors, to our knowledge the first study of its kind. We found intracortical axons were significantly longer than optimal. The temporal cost of cortical axons was also suboptimal though far superior to wire-minimized arbors. We discovered that cortical axon branching appears to promote a low temporal dispersion of axonal latencies and a tight relationship between cortical distance and axonal latency. In addition, inhibitory basket cell axonal latencies may occur within a much narrower temporal window than excitatory spiny cell axons, which may help boost signal detection. Thus, to optimize neuronal network communication we find that a modest excess of axonal wire is traded-off to enhance arbor temporal economy and precision. Our results offer insight into the principles of brain organization and communication in and development of grey matter, where temporal precision is a crucial prerequisite for coincidence detection, synchronization and rapid network oscillations. PMID- 20300652 TI - Quantitative comparison of catalytic mechanisms and overall reactions in convergently evolved enzymes: implications for classification of enzyme function. AB - Functionally analogous enzymes are those that catalyze similar reactions on similar substrates but do not share common ancestry, providing a window on the different structural strategies nature has used to evolve required catalysts. Identification and use of this information to improve reaction classification and computational annotation of enzymes newly discovered in the genome projects would benefit from systematic determination of reaction similarities. Here, we quantified similarity in bond changes for overall reactions and catalytic mechanisms for 95 pairs of functionally analogous enzymes (non-homologous enzymes with identical first three numbers of their EC codes) from the MACiE database. Similarity of overall reactions was computed by comparing the sets of bond changes in the transformations from substrates to products. For similarity of mechanisms, sets of bond changes occurring in each mechanistic step were compared; these similarities were then used to guide global and local alignments of mechanistic steps. Using this metric, only 44% of pairs of functionally analogous enzymes in the dataset had significantly similar overall reactions. For these enzymes, convergence to the same mechanism occurred in 33% of cases, with most pairs having at least one identical mechanistic step. Using our metric, overall reaction similarity serves as an upper bound for mechanistic similarity in functional analogs. For example, the four carbon-oxygen lyases acting on phosphates (EC 4.2.3) show neither significant overall reaction similarity nor significant mechanistic similarity. By contrast, the three carboxylic-ester hydrolases (EC 3.1.1) catalyze overall reactions with identical bond changes and have converged to almost identical mechanisms. The large proportion of enzyme pairs that do not show significant overall reaction similarity (56%) suggests that at least for the functionally analogous enzymes studied here, more stringent criteria could be used to refine definitions of EC sub-subclasses for improved discrimination in their classification of enzyme reactions. The results also indicate that mechanistic convergence of reaction steps is widespread, suggesting that quantitative measurement of mechanistic similarity can inform approaches for functional annotation. PMID- 20300653 TI - Non-linear neuronal responses as an emergent property of afferent networks: a case study of the locust lobula giant movement detector. AB - In principle it appears advantageous for single neurons to perform non-linear operations. Indeed it has been reported that some neurons show signatures of such operations in their electrophysiological response. A particular case in point is the Lobula Giant Movement Detector (LGMD) neuron of the locust, which is reported to locally perform a functional multiplication. Given the wide ramifications of this suggestion with respect to our understanding of neuronal computations, it is essential that this interpretation of the LGMD as a local multiplication unit is thoroughly tested. Here we evaluate an alternative model that tests the hypothesis that the non-linear responses of the LGMD neuron emerge from the interactions of many neurons in the opto-motor processing structure of the locust. We show, by exposing our model to standard LGMD stimulation protocols, that the properties of the LGMD that were seen as a hallmark of local non-linear operations can be explained as emerging from the dynamics of the pre-synaptic network. Moreover, we demonstrate that these properties strongly depend on the details of the synaptic projections from the medulla to the LGMD. From these observations we deduce a number of testable predictions. To assess the real-time properties of our model we applied it to a high-speed robot. These robot results show that our model of the locust opto-motor system is able to reliably stabilize the movement trajectory of the robot and can robustly support collision avoidance. In addition, these behavioural experiments suggest that the emergent non-linear responses of the LGMD neuron enhance the system's collision detection acuity. We show how all reported properties of this neuron are consistently reproduced by this alternative model, and how they emerge from the overall opto motor processing structure of the locust. Hence, our results propose an alternative view on neuronal computation that emphasizes the network properties as opposed to the local transformations that can be performed by single neurons. PMID- 20300654 TI - Drosophila Xpd regulates Cdk7 localization, mitotic kinase activity, spindle dynamics, and chromosome segregation. AB - The trimeric CAK complex functions in cell cycle control by phosphorylating and activating Cdks while TFIIH-linked CAK functions in transcription. CAK also associates into a tetramer with Xpd, and our analysis of young Drosophila embryos that do not require transcription now suggests a cell cycle function for this interaction. xpd is essential for the coordination and rapid progression of the mitotic divisions during the late nuclear division cycles. Lack of Xpd also causes defects in the dynamics of the mitotic spindle and chromosomal instability as seen in the failure to segregate chromosomes properly during ana- and telophase. These defects appear to be also nucleotide excision repair (NER) independent. In the absence of Xpd, misrouted spindle microtubules attach to chromosomes of neighboring mitotic figures, removing them from their normal location and causing multipolar spindles and aneuploidy. Lack of Xpd also causes changes in the dynamics of subcellular and temporal distribution of the CAK component Cdk7 and local mitotic kinase activity. xpd thus functions normally to re-localize Cdk7(CAK) to different subcellular compartments, apparently removing it from its cell cycle substrate, the mitotic Cdk. This work proves that the multitask protein Xpd also plays an essential role in cell cycle regulation that appears to be independent of transcription or NER. Xpd dynamically localizes Cdk7/CAK to and away from subcellular substrates, thereby controlling local mitotic kinase activity. Possibly through this activity, xpd controls spindle dynamics and chromosome segregation in our model system. This novel role of xpd should also lead to new insights into the understanding of the neurological and cancer aspects of the human XPD disease phenotypes. PMID- 20300655 TI - Bias and evolution of the mutationally accessible phenotypic space in a developmental system. AB - Genetic and developmental architecture may bias the mutationally available phenotypic spectrum. Although such asymmetries in the introduction of variation may influence possible evolutionary trajectories, we lack quantitative characterization of biases in mutationally inducible phenotypic variation, their genotype-dependence, and their underlying molecular and developmental causes. Here we quantify the mutationally accessible phenotypic spectrum of the vulval developmental system using mutation accumulation (MA) lines derived from four wild isolates of the nematodes Caenorhabditis elegans and C. briggsae. The results confirm that on average, spontaneous mutations degrade developmental precision, with MA lines showing a low, yet consistently increased, proportion of developmental defects and variants. This result indicates strong purifying selection acting to maintain an invariant vulval phenotype. Both developmental system and genotype significantly bias the spectrum of mutationally inducible phenotypic variants. First, irrespective of genotype, there is a developmental bias, such that certain phenotypic variants are commonly induced by MA, while others are very rarely or never induced. Second, we found that both the degree and spectrum of mutationally accessible phenotypic variation are genotype dependent. Overall, C. briggsae MA lines exhibited a two-fold higher decline in precision than the C. elegans MA lines. Moreover, the propensity to generate specific developmental variants depended on the genetic background. We show that such genotype-specific developmental biases are likely due to cryptic quantitative variation in activities of underlying molecular cascades. This analysis allowed us to identify the mutationally most sensitive elements of the vulval developmental system, which may indicate axes of potential evolutionary variation. Consistent with this scenario, we found that evolutionary trends in the vulval system concern the phenotypic characters that are most easily affected by mutation. This study provides an empirical assessment of developmental bias and the evolution of mutationally accessible phenotypes and supports the notion that such bias may influence the directions of evolutionary change. PMID- 20300656 TI - Arginylation-dependent neural crest cell migration is essential for mouse development. AB - Coordinated cell migration during development is crucial for morphogenesis and largely relies on cells of the neural crest lineage that migrate over long distances to give rise to organs and tissues throughout the body. Recent studies of protein arginylation implicated this poorly understood posttranslational modification in the functioning of actin cytoskeleton and in cell migration in culture. Knockout of arginyltransferase (Ate1) in mice leads to embryonic lethality and severe heart defects that are reminiscent of cell migration dependent phenotypes seen in other mouse models. To test the hypothesis that arginylation regulates cell migration during morphogenesis, we produced Wnt1-Cre Ate1 conditional knockout mice (Wnt1-Ate1), with Ate1 deletion in the neural crest cells driven by Wnt1 promoter. Wnt1-Ate1 mice die at birth and in the first 2-3 weeks after birth with severe breathing problems and with growth and behavioral retardation. Wnt1-Ate1 pups have prominent defects, including short palate and altered opening to the nasopharynx, and cranial defects that likely contribute to the abnormal breathing and early death. Analysis of neural crest cell movement patterns in situ and cell motility in culture shows an overall delay in the migration of Ate1 knockout cells that is likely regulated by intracellular mechanisms rather than extracellular signaling events. Taken together, our data suggest that arginylation plays a general role in the migration of the neural crest cells in development by regulating the molecular machinery that underlies cell migration through tissues and organs during morphogenesis. PMID- 20300657 TI - MiR-218 inhibits invasion and metastasis of gastric cancer by targeting the Robo1 receptor. AB - MicroRNAs play key roles in tumor metastasis. Here, we describe the regulation and function of miR-218 in gastric cancer (GC) metastasis. miR-218 expression is decreased along with the expression of one of its host genes, Slit3 in metastatic GC. However, Robo1, one of several Slit receptors, is negatively regulated by miR 218, thus establishing a negative feedback loop. Decreased miR-218 levels eliminate Robo1 repression, which activates the Slit-Robo1 pathway through the interaction between Robo1 and Slit2, thus triggering tumor metastasis. The restoration of miR-218 suppresses Robo1 expression and inhibits tumor cell invasion and metastasis in vitro and in vivo. Taken together, our results describe a Slit-miR-218-Robo1 regulatory circuit whose disruption may contribute to GC metastasis. Targeting miR-218 may provide a strategy for blocking tumor metastasis. PMID- 20300658 TI - HP1 recruitment in the absence of argonaute proteins in Drosophila. AB - Highly repetitive and transposable element rich regions of the genome must be stabilized by the presence of heterochromatin. A direct role for RNA interference in the establishment of heterochromatin has been demonstrated in fission yeast. In metazoans, which possess multiple RNA-silencing pathways that are both functionally distinct and spatially restricted, whether RNA silencing contributes directly to heterochromatin formation is not clear. Previous studies in Drosophila melanogaster have suggested the involvement of both the AGO2-dependent endogenous small interfering RNA (endo-siRNA) as well as Piwi-interacting RNA (piRNA) silencing pathways. In order to determine if these Argonaute genes are required for heterochromatin formation, we utilized transcriptional reporters and chromatin immunoprecipitation of the critical factor Heterochromatin Protein 1 (HP1) to monitor the heterochromatic state of piRNA clusters, which generate both endo-siRNAs and the bulk of piRNAs. Surprisingly, we find that mutation of AGO2 or piwi increases silencing at piRNA clusters corresponding to an increase of HP1 association. Furthermore, loss of piRNA production from a single piRNA cluster results in genome-wide redistribution of HP1 and reduction of silencing at a distant heterochromatic site, suggesting indirect effects on HP1 recruitment. Taken together, these results indicate that heterochromatin forms independently of endo-siRNA and piRNA pathways. PMID- 20300660 TI - Cystic fibrosis is a risk factor for celiac disease. AB - BACKGROUND: The coexistence of cystic fibrosis (CF) and celiac disease (CD) has been reported. To our knowledge there is no study directly comparing the incidence of CD in CF patients to that in the general population at the same time. There is no published data on genetic predisposition to CD in CF patients either. Therefore, in the present study we aimed to assess the genetic predisposition to CD and its incidence in CF patients comparing it to data from the general population. PATIENTS AND METHODS: Two hundred eighty-two CF patients were enrolled in the study. In 230 CF patients the genetic predisposition to CD (the presence of HLA-DQ2/ DQ8) was assessed. In all CF patients, serological screening for CD was conducted. In patients with positive antiendomysial antibodies (EMA) gastroduenoscopy was offered. Intestinal histology was classified according to modified Marsh criteria. The results of serological CD screening in 3235 Polish schoolchildren and HLA-DQ typing in 200 healthy subjects (HS) were used for comparison. RESULTS: Positive EMA was found in 2.84% of the studied CF patients. The incidence of proven CD was 2.13%. The incidence of CD as well as positive serological screening were significantly more frequent in the CF group than in the general population. The frequency of CD-related HLA-DQ alleles in CF and HS did not differ. CONCLUSIONS: Genetic predisposition to celiac disease in cystic fibrosis patients is similar to that of the general population. However, our results suggest that cystic fibrosis is a risk factor for celiac disease development. PMID- 20300659 TI - The human polyoma JC virus agnoprotein acts as a viroporin. AB - Virus infections can result in a range of cellular injuries and commonly this involves both the plasma and intracellular membranes, resulting in enhanced permeability. Viroporins are a group of proteins that interact with plasma membranes modifying permeability and can promote the release of viral particles. While these proteins are not essential for virus replication, their activity certainly promotes virus growth. Progressive multifocal leukoencephalopathy (PML) is a fatal demyelinating disease resulting from lytic infection of oligodendrocytes by the polyomavirus JC virus (JCV). The genome of JCV encodes six major proteins including a small auxiliary protein known as agnoprotein. Studies on other polyomavirus agnoproteins have suggested that the protein may contribute to viral propagation at various stages in the replication cycle, including transcription, translation, processing of late viral proteins, assembly of virions, and viral propagation. Previous studies from our and other laboratories have indicated that JCV agnoprotein plays an important, although as yet incompletely understood role in the propagation of JCV. Here, we demonstrate that agnoprotein possesses properties commonly associated with viroporins. Our findings demonstrate that: (i) A deletion mutant of agnoprotein is defective in virion release and viral propagation; (ii) Agnoprotein localizes to the ER early in infection, but is also found at the plasma membrane late in infection; (iii) Agnoprotein is an integral membrane protein and forms homo-oligomers; (iv) Agnoprotein enhances permeability of cells to the translation inhibitor hygromycin B; (v) Agnoprotein induces the influx of extracellular Ca(2+); (vi) The basic residues at amino acid positions 8 and 9 of agnoprotein key are determinants of the viroporin activity. The viroporin-like properties of agnoprotein result in increased membrane permeability and alterations in intracellular Ca(2+) homeostasis leading to membrane dysfunction and enhancement of virus release. PMID- 20300661 TI - Boric acid as a protector against paclitaxel genotoxicity. AB - Paclitaxel (PAC) is an anticancer drug used for treatments of breast, ovarian and lung cancers. However, little data is available in the literature on its potential genotoxicity on healthy human cells. On the other hand, boron deficiency and supplementation exert important biological effects in human and animal tissues. The biological effects of dietary boron are defined, but its interaction with PAC is not known for therapeutic uses. The aim of the present study was to determine whether boric acid (BA) confer a protection against PAC genotoxicity. After the application of PAC (10 or 20 microg/l) and BA (2.5 or 5 mg/l), the genotoxic effects were assessed by sister chromatid exchange (SCE) and micronucleus (MN) tests in human blood cultures. We also analyzed nuclear division index (NDI) in peripheral lymphocytes. Our results showed that PAC significantly (P<0.05) increased the frequencies of SCEs and the formations of MNs in peripheral lymphocytes as compared to controls. PAC decreased the nuclear division index in lymphocyte cultures. Boric acid did not show cytotoxic or genotoxic effects at the concentrations tested. Furthermore, the PAC-induced increases in the genotoxicity and cytotoxicity indices were diminished by the addition of BA. The present study suggests for the first time that BA can prevent the genotoxicity of PAC on human lymphocytes. PMID- 20300662 TI - N-myc downstream regulated 1 gene and its place in the cellular machinery. AB - The exact function of the protein product of N-myc downstream regulated 1 gene (NDRG1) is unclear. Depending on the tissue type the NDRG1 protein is localized in the cytoplasm, nucleus, mitochondrion or membranes. Moreover, the expression of NDRG1 may be altered by several factors such as hypoxia, heavy metals, DNA damage, hormones, oncogene, and tumor-suppressor genes. A number of studies emphasize the role of NDRG1 in cancerogenesis. Presumably NDRG1 participates in angiogenesis, metastases, and mechanisms leading to anti-cancer drug resistance. This review summarizes current knowledge about the NDRG1 gene and the position of NDRG1 protein in the cellular machinery. The role of NDRG1 in cancer pathogenesis and its possible usefulness as a prognostic factor for patients with cancer is also discussed. PMID- 20300663 TI - Cloning and characterization of the yak gene coding for calpastatin and in silico analysis of its putative product. AB - The calcium-activated neutral proteases, mu- and m-calpain, along with their inhibitor, calpastatin, have been demonstrated to mediate a variety of Ca(2+) dependent processes including signal transduction, cell proliferation, cell cycle progression, differentiation, apoptosis, membrane fusion, platelet activation and skeletal muscle protein degradation. The cDNA coding for yak calpastatin was amplified and cloned by RT-PCR to investigate and characterize the nucleotide/amino-acid sequence and to predict structure and function of the calpastatin. The present study suggests that the yak calpastatin gene encodes a protein of 786 amino acids that shares 99 % sequence identity with the amino-acid sequence of cattle calpastatin, and that the yak protein is composed of an N terminal region (domains L and XL) and four repetitive homologous C-terminal domains (d1-d4), in which several prosite motifs are present including short peptide L54-64 (EVKPKEHTEPK in domain L) and GXXE/ DXTIPPXYR (in subdomain B), where X is a variable amino acid. Our results suggest the existence of other functional sites including potential phosphorylation sites for protein kinase C, cAMP- and cGMP-dependent protein kinase, casein kinase II, as well as N myristoylation and amidation sites that play an important role in molecular regulation of the calpain/calpastatin system. The regulation of the calpain/calpastatin system is determined by the interaction between dIV and dVI in calpains and subdomains A, B, and C in calpastatin. PMID- 20300667 TI - Lost in translation. PMID- 20300668 TI - High-throughput automated droplet microfluidic system for screening of reaction conditions. AB - We demonstrate a new droplet on demand (DOD) technique and an integrated system for scanning of arbitrary combinations of 3 miscible solutions in approximately 1.5 microL droplets at 3 Hz. The DOD system uses standard electromagnetic valves that are external to the microfluidic chip. This feature makes up for modularity, simplicity of assembly and compatibility with virtually any microfluidic chip and yields an on-chip footprint of less than 1 mm(2). A novel protocol for formation of DOD enables generation of an arbitrarily large range of volumes of droplets at a maximum operational frequency of approximately 30 Hz. The integrated system that we demonstrate can be used to scan up to 10,000 conditions of chemical and biochemical reactions per hour using approximately 10 mL of solutions in total. PMID- 20300669 TI - Benchmarking methods of enhanced heavy oil recovery using a microscaled bead pack. AB - A microscaled bead-pack is capable of simulating two-phase fractional flow within porous media and can be applied to simulating interactions between fluids and geological materials under dynamic conditions within the laboratory. PMID- 20300670 TI - A microfluidic chip-compatible bioassay based on single-molecule detection with high sensitivity and multiplexing. AB - Many applications in pharmaceutical development, clinical diagnostics, and biological research demand rapid detection of multiple analytes (multiplexed detection) in a minimal volume. This need has led to the development of several novel array-based sensors. The most successful of these so far have been suspension arrays based on polystyrene beads. However, the 5 microm beads used for these assays are incompatible with most microfluidic chip technologies, mostly due to clogging problems. The challenge, then, is to design a detection particle that has high information content (for multiplexed detection), is compatible with miniaturization, and can be manufactured easily at low cost. DNA is a solid molecular wire that is easily produced and manipulated, which makes it a useful material for nanoparticles. DNA molecules are very information-rich, readily deformable, and easily propagated. We exploit these attributes in a suspension array sensor built from specialized recombinant DNA, Digital DNA, that carries both specific analyte-recognition units, and a geometrically encoded identification pattern. Here we show that this sensor combines high multiplexing with high sensitivity, is biocompatible, and has sufficiently small particle size to be used within microfluidic chips that are only 1 microm deep. We expect this technology will be the foundation of a broadly applicable technique to identify and quantitate proteins, nucleic acids, viruses, and toxins simultaneously in a minimal volume. PMID- 20300671 TI - High-throughput fluorescence detection using an integrated zone-plate array. AB - Microfluidic devices enable massive parallelization of sample manipulation and delivery, but a similarly parallelized and integrated optical detection system does not yet exist. Standard large numerical aperture wide field or scanning optical systems are not capable of the large field of view and detection sensitivity required to collect fluorescence from parallel arrays of microfluidic devices. Instead, we present a fluorescence measurement platform based on a microfabricated zone-plate array integrated into a parallelized microfluidic device. The zone-plate array is orientated so that a single high numerical aperture zone plate is aligned to read out the fluorescence from each of 64 output channels of a drop-making device. The parallelization of microfluidics and optics produces an integrated system capable of analysis of nearly 200,000 drops per second. PMID- 20300672 TI - Optimization of microfluidic single cell trapping for long-term on-chip culture. AB - The poor efficiency of microfluidic single cell trapping is currently restricting the full potential of state-of-the-art single cell analyses. Using fluid dynamics simulations in combination with particle image velocimetry to systematically optimize trap architectures, we present a microfluidic chip with enhanced single cell trapping and on-chip culture performance. Upon optimization of trap geometries, we measured trapping efficiencies of up to 97%. Our device also enables the stable, relatively long-term culture of individual non-adherent mammalian cells in high-throughput without a significant decrease in cell viability. As a first application of this platform we demonstrate the automated separation of the two daughter cells generated upon single cell division. The reliable trapping and re-trapping of mammalian cells should for example provide the fundament for novel types of investigations in stem cell and tumour cell biology, which depend on reliable tracking of genealogical relationships such as in stem cell lineage tracking. PMID- 20300673 TI - Air-stable supported membranes for single-cell cytometry on PDMS microchips. AB - Protein-reinforced supported bilayer membranes (rSBMs) composed of phosphatidylcholine (PC), biotin-PE and Neutravidin were used to coat hybrid microchips composed of polydimethylsiloxane (PDMS) and glass. Since the coatings required a freshly oxidized, hydrophilic substrate, a novel method to rapidly connect reservoirs using plasma oxidation was first developed and found to support up to 5.2 N cm(-2) (1.5 N) pull-off force. rSBMs were then assembled in the oxidized hydrophilic channels. The electroosmotic mobility (mu(eo)) of rSBM coated channels was measured over a 3 h time to evaluate the stability of the coatings for microchip electrophoresis. rSBM-coated microchips with a simple cross-design had excellent properties for microchip separations, yielding efficiencies of up to 700,000 plates m(-1) for fluorescent dyes and peptides. The separation performance of rSBM and PC-coated channels was evaluated after repeatedly drying and rehydrating the channels. The separation efficiency of fluorescein on PC-coated devices decreased by 40% after one dehydration cycle and nearly 75% after 3 cycles. In contrast for rSBM-coated devices there was no significant change in the fluorescein efficiency until the third cycle (10% decreased efficiency). rSBM-coated channels were also markedly more stable when placed in a dehydrated state during long-term storage compared to PC-coated channels, and showed reduced chip failure and no reduction in performance for up to one month of dehydrated storage. Finally, rSBM-coated devices were used to perform single-cell cytometry. Microchips that had been dehydrated, stored two weeks, and rehydrated prior to use demonstrated similar performance to newly coated devices for the separation of fluorescein and carboxyfluorescein from single cells. Thus rSBM-coated devices were rugged withstanding electric fields, prolonged storage under dehydrated conditions, and biofouling by cellular constituents while maintaining excellent separation performance. PMID- 20300674 TI - Numerical modeling and experimental validation of uniform microchamber filling in centrifugal microfluidics. AB - In this paper, a comprehensive approach to numerical and experimental analysis of microchamber filling in centrifugal microfluidics is presented. In the development of micro total analysis systems, it is often necessary to achieve complete, uniform filling of relatively large microchambers, such as those needed for nucleic acid amplification or detection. With centrifugal devices, these large microchambers must often be orientated perpendicularly to the direction of centrifugal force and are usually bounded by materials with varying surface properties. The resulting fluidic flow in such systems can be complex and is not well characterized. To gain further insight into complex fluidic behavior on centrifugal microfluidic platforms, numerical modeling using the Volume of Fluids method is performed to simulate microchamber filling in a centrifugal microfluidic device with integrated sample preparation, amplification, and detection capabilities. Parametric analyses are performed using numerical models to predict microchamber filling behavior for a range of pressure conditions. High speed flow visualization techniques are used to track the liquid meniscus during filling of the microchambers, and comparison to the numerical predictions for experimental validation is achieved by analyzing the liquid volume fraction as a function of the non-dimensional temporal profile during filling. When channel filling profiles are compared, the numerical model predictions utilizing static conditions are in strong agreement with the experimental data. When dynamic modeling conditions are used, the numerical predictions are extremely accurate as compared to the experimental data. PMID- 20300675 TI - Microfluidic lab-on-a-foil for nucleic acid analysis based on isothermal recombinase polymerase amplification (RPA). AB - For the first time we demonstrate a self-sufficient lab-on-a-foil system for the fully automated analysis of nucleic acids which is based on the recently available isothermal recombinase polymerase amplification (RPA). The system consists of a novel, foil-based centrifugal microfluidic cartridge including prestored liquid and dry reagents, and a commercially available centrifugal analyzer for incubation at 37 degrees C and real-time fluorescence detection. The system was characterized with an assay for the detection of the antibiotic resistance gene mecA of Staphylococcus aureus. The limit of detection was <10 copies and time-to-result was <20 min. Microfluidic unit operations comprise storage and release of liquid reagents, reconstitution of lyophilized reagents, aliquoting the sample into < or = 30 independent reaction cavities, and mixing of reagents with the DNA samples. The foil-based cartridge was produced by blow molding and sealed with a self-adhesive tape. The demonstrated system excels existing PCR based lab-on-a-chip platforms in terms of energy efficiency and time to-result. Applications are suggested in the field of mobile point-of-care analysis, B-detection, or in combination with continuous monitoring systems. PMID- 20300676 TI - Biosensor system-on-a-chip including CMOS-based signal processing circuits and 64 carbon nanotube-based sensors for the detection of a neurotransmitter. AB - We developed a carbon nanotube (CNT)-based biosensor system-on-a-chip (SoC) for the detection of a neurotransmitter. Here, 64 CNT-based sensors were integrated with silicon-based signal processing circuits in a single chip, which was made possible by combining several technological breakthroughs such as efficient signal processing, uniform CNT networks, and biocompatible functionalization of CNT-based sensors. The chip was utilized to detect glutamate, a neurotransmitter, where ammonia, a byproduct of the enzymatic reaction of glutamate and glutamate oxidase on CNT-based sensors, modulated the conductance signals to the CNT-based sensors. This is a major technological advancement in the integration of CNT based sensors with microelectronics, and this chip can be readily integrated with larger scale lab-on-a-chip (LoC) systems for various applications such as LoC systems for neural networks. PMID- 20300677 TI - Vacuum membrane distillation by microchip with temperature gradient. AB - A multilayered microchip (25 x 95 mm) used for vacuum distillation is designed, fabricated and tested by rectification of a water-methanol mixture. The polymer chip employs a cooling channel to generate a temperature gradient along a distillation channel below, which is separated into a channel (72 microm deep) for liquid phase and a channel (72 microm deep) for vapor phase by an incorporated microporous poly(tetrafluoroethylene) (PTFE) membrane. The temperature gradient is controlled by adjusting hotplate temperature and flow rate of cooling water to make the temperatures in the stripping section higher than the increasing boiling points of the water-enriched liquids and the temperatures in the rectifying section lower than the decreasing dew points of the methanol-enriched vapors. The effects of temperature gradient, feed composition, feed flow rate and membrane pore size on the micro distillation are also investigated. A theoretical plate number up to 1.8 is achieved at the optimum conditions. PMID- 20300678 TI - Controlled reagent transport in disposable 2D paper networks. AB - Recent reports have demonstrated the multi-analyte detection capability of paper networks with multiple outlets per inlet. In this report, we focus on the capabilities of 2D paper networks with multiple inlets per outlet and demonstrate the controlled transport of reagents within paper devices. Specifically, we demonstrate methods of controlling fluid transport using the geometry of the network and dissolvable barriers. Finally, we discuss the implications for higher sensitivity detection using this type of 2D paper network. PMID- 20300681 TI - A clustering approach to segmenting users of internet-based risk calculators. AB - BACKGROUND: Risk calculators are widely available Internet applications that deliver quantitative health risk estimates to consumers. Although these tools are known to have varying effects on risk perceptions, little is known about who will be more likely to accept objective risk estimates. OBJECTIVE: To identify clusters of online health consumers that help explain variation in individual improvement in risk perceptions from web-based quantitative disease risk information. METHODS: A secondary analysis was performed on data collected in a field experiment that measured people's pre-diabetes risk perceptions before and after visiting a realistic health promotion website that provided quantitative risk information. K-means clustering was performed on numerous candidate variable sets, and the different segmentations were evaluated based on between-cluster variation in risk perception improvement. RESULTS: Variation in responses to risk information was best explained by clustering on pre-intervention absolute pre diabetes risk perceptions and an objective estimate of personal risk. Members of a high-risk overestimater cluster showed large improvements in their risk perceptions, but clusters of both moderate-risk and high-risk underestimaters were much more muted in improving their optimistically biased perceptions. CONCLUSIONS: Cluster analysis provided a unique approach for segmenting health consumers and predicting their acceptance of quantitative disease risk information. These clusters suggest that health consumers were very responsive to good news, but tended not to incorporate bad news into their self-perceptions much. These findings help to quantify variation among online health consumers and may inform the targeted marketing of and improvements to risk communication tools on the Internet. PMID- 20300682 TI - Long-term impact of physician encoding on detail and number of recorded diagnoses. Support by a speciality specific list of diseases. AB - OBJECTIVES: To improve the recording of diagnostic discharge data, pediatricians encoded diagnostic information as part of discharge letter writing supported by a pediatric list of ICD-9-CM-based codes. We evaluated the effect of this new policy on level of detail and number of recorded diagnoses. METHODS: We compared proportions of specific principal diagnoses and numbers of secondary diagnoses of the four years before with the eight years after introduction. RESULTS: Immediately after introduction, half of the diagnoses for which both generic and specific codes existed was coded specific. In later years this proportion remained stable at 0.35 (p <0.05). Diagnoses that fall under the pediatrician's own subspecialty had more often a specific code than diagnoses that do not. The mean number of secondary diagnoses per admission increased from 0.7 before introduction to 1.4 in the third year after introduction (p <0.05) but gradually fell back to 0.7. This increase and decrease was mainly due to diagnoses that did not fall under the pediatrician's own subspecialty. The extra codes in individual discharge summaries had added informational value. CONCLUSIONS: Discharge letter linked encoding by pediatricians supported by a pediatric list of diseases leads initially to increased detail and number of diagnoses with added informational value. When attention diminishes, especially the level of detail and number of secondary diagnoses that do not fall under one's own subspecialty decrease. The level of detail of principal diagnoses remains stable because of the advantage for pediatricians of having specific diagnostic codes falling under their own subspecialty. PMID- 20300683 TI - [Comparison of the effects resulted by modified maxillary oblique plate and Twin block in advancing mandible]. AB - URPOSE: The aim of this study was to evaluate the effects resulted by modified maxillary oblique plate in advancing mandible. METHODS: Twelve Class II division II cases (4 males, 8 females) with mandibular retrusion were selected as group 1 aligned by fixed appliances in the upper arches, and their mandibles were advanced by the modified maxillary oblique plates. Meanwhile, twelve Class II division II cases (5 males, 7 females) with mandibular retrusion were selected as group 2 treated with the Twin-block. The average age was 11 years 8 months in group 1, and 11 years 6 months in group 2. The effects of advancing mandible were compared between the two groups by analyzing cephalometric films before and after treatment with SAS6.0 software package. RESULTS: Mandibular advancement was achieved in the two groups. Mandibular anterior teeth labial tipping was more obvious in group 1 than in group 2, but without significant those(P>0.05). Both mesial and occlusal movements of the lower first molar in group 2 were more significant than those in group 1 (P<0.05). CONCLUSIONS: Based on the results, the modified maxillary oblique plate is an excellent appliance for the advancing mandible in Class II division II cases with the advantages of economics, simplification and effectiveness. PMID- 20300684 TI - [Maxillofacial 3-dimensional morphological analysis for patients with Class III malocclusion and facial asymmetry]. AB - PURPOSE: To investigate the skeletodental factors relating to the chin point deviation of facial asymmetry in skeletal Class III malocclusion patients using three-dimensional computed tomography. METHODS: Forty-one adult female patients with class III malocclusion, who underwent three-dimensional CT examination before orthodontics treatment, were assigned as group of symmetry or group of asymmetry according to the amount of chin point deviation from the facial midline. Midfacial and mandibular variables were measured. The data was analyzed with SPSS13.0 software package. RESULTS: Patients in the group of asymmetry showed higher positions of the upper canine and first molar, shorter ramus height, more superior positioning of gonion on the deviated side, more mesial and frontal inclination of the ramus, medial and frontal positioning of gonion on the opposite side than the group of symmetry. Menton deviation correlated significantly with the difference of ramus height between the 2 sides ramus, ramus height in the deviated side and other skeletodental factors. CONCLUSIONS: Facial asymmetry in Class III patients is due to the overgrowth,frontal and mesial inclination of the ramus in the opposite side. PMID- 20300685 TI - [Investigation of dental manpower in non-public medical units in Shanghai]. AB - PURPOSE: A mass survey on dental manpower was made in non-public medical units in Shanghai in 2007 to analyze the number,structure,composition,distribution,equipment and out-patient departments (OPDs) of dental manpower and to approach the existing problems. The purpose was to provide information for investigating the dental manpower in Shanghai and the reasonable allocation and utilization of the dental manpower in Shanghai. METHODS: A mass survey on dental manpower was made in non-public medical units in Shanghai in 2007 by means of questionnaire investigation, which included direct interview and telephone interview. The survey content included the number,structure,composition,distribution,equipment and out-patient departments(OPDs) of dental manpower in non-public medical units in Shanghai. RESULTS: There were 488 non-public dental units and 1172 dentists, 848 nurses, 79 technicians, 1377 dental units in Shanghai. 86.9% of the dentists were young and middle-aged, 44.88% of them had middle level professional tiles, 51.28% of them had university educational background and the specialty of 89.59% of the dentists was general dentistry. 81.84% of the nurses had primary professional tiles and 75.47% of the nurses' educational background was below the junior college degree. The ratio of the dentists to nurses to technicians was 15:11:1. The non-public dental units and dental manpower resources were concentrated in the downtown with 54.1% of the units, 57.85% of the dentists, 61.57% of the nurses and 79.75% of the technicians there. The total amount of dental out-patient departments DOPDs in non-public medical units in Shanghai in 2007 was 976,650, 61.42% in the downtown. 38.97% of the units thought the DOPDs were few or less while 57.82% considered it was just right. Among them, 20.04% of the units thought their units needed dentists. Among them, 68.09% of the units needed general dentists. CONCLUSIONS: Dental manpower in non-public medical units in Shanghai concentrates in the downtown and Pudong new area. The structure and composition are reasonable. Most of the patients visit the non-public units in the downtown for treatment, many units think their amount of out-patient is small and they need general dentists mostly. PMID- 20300686 TI - [Application of palatal base combined with shield above floor of mouth for restoration of acquired mandibular defect with glossectomy: report of one case]. AB - PURPOSE: To evaluate the prosthetic results of application of palatal base combined with shield above the floor of mouth for restoration of acquired mandibular defect with glossectomy. METHODS: Palatal base with four wrought clasps was designed for the upper prostheses. Shield just above the floor of the mouth and buccal mucosa was fabricated to support the buccal mucosa and muscle. Then the upper and lower prostheses were linked by using thermal curing acrylic resin on the left and right side. RESULTS: Good retention of the prostheses was obtained. The appearance of the patient was remarkably improved. Depression of the lower lip was improved. Oral function was enhanced. CONCLUSIONS: Better prosthetic results could be obtained by using palatal base combined with shield above the floor of mouth for restoration of acquired mandibular defect with glossectomy. PMID- 20300687 TI - [Application of digital photography in color matching of porcelain restoration in special color teeth]. AB - PURPOSE: To evaluate the clinical application of digital photography in special color teeth, and to explore the role and the problems s of digital photos to improve cosmetic effect. METHODS: Digital photography combined visual color matching was applied in 50 cases with special color teeth in ceramic restorations selected randomly. Then the satisfactory degree of the patients and dentists was evaluated and the value of L*a*b* between prosthesis and its neighbors was collected by self-developed software Dental ImgShop. Chroma (C(ab) )and hue (h(ab) degrees ) were calculated according to the value of a and b. The data was analyzed with paired t test using SAS6.12 software package, so as chromatic aberration (deltaE). RESULTS: The satisfactory degree of the patients was 98%, and the satisfaction degree of the dentists was 94%. The range of L, a ,b C(ab), h(ab) degrees of special color teeth was 54.50-92.29, -0.97-8.12,-0.73-20.85,0.85 21.34,29.73-89.20, respectively. There was no significant difference between the prosthesis and their neighbors statistically (P>0.05). The mean value of chromatic aberration (deltaE) was 0.948(0.136-3.45), and only 3 cases were unacceptable (deltaE>/=2). CONCLUSIONS: Digital photography could record and transmit the color information of special color teeth more exactly, and could improve the patients satisfaction and the cosmetic effect in color measuring. Supported by Research Fund of Natural Science for Young Scholars of Minhang Central Hospital. PMID- 20300688 TI - [Ectopic meningioma in oral and maxillofacial region: report of 23 cases]. AB - PURPOSE: To analyse the clinical features and treatment of ectopic meningioma (EM) in oral and maxillofacial region. METHODS: Twenty-three cases of EM in the oral and maxillofacial region from 1990 to 2008 were reviewed. The clinical features, image findings, surgical treatment and follow-up results were analyzed. RESULTS: The median age of these patients was 37 years old and there was no gender predilection, but there were more female patients in the group of over 40 years old. The primary sites of the tumor were parapharyngeal space(13), infratemporal space/ pterygopalatine space(5), temporal region(3),orbital area (1) and buccal mucosa(1). The CT image of EM in the oral and maxillofacial region was similar to that in the brain. All 23 cases underwent surgical treatment, seventeen cases underwent the tumor totally resected and 6 cases underwent partially resected. Twelve cases were followed up, in which 3 cases recurred and 8 cases had a long-term nerve injury. CONCLUSIONS: EM in the oral and maxillofacial region mainly occurs in adolescent, middle-aged patients and females over 40 years old. The predilection site of the tumor is the deep space of oral and maxillofacial region with adherence to the cervical sheath and lower cranial nerves. Preoperative CT scan is helpful for diagnosis. The main choice of treatment is total resection. The main complication is nerve injury. PMID- 20300689 TI - [Investigation of dental manpower in public medical units in Shanghai]. AB - PURPOSE: To provide information for investigating the dental manpower of in the number, composition, distribution, equipment and out-patient departments (OPDs) in Shanghai and the reasonable allocation and utilization of the dental manpower in Shanghai. METHODS: A mass survey on dental manpower was made in public medical units in Shanghai in 2007 by means of questionnaire investigation, which included direct interview and telephone interview. The survey content included the number,structure,composition,distribution,equipment and out-patient departments of dental manpower in public medical units in Shanghai. RESULTS: There were 364 public dental medical units distributing 26 tertiary hospitals, 99 grade 2 hospitals, 239 primary hospitals with 2046 dentists, 634 nurses, 281 technicians and 2010 dental units in Shanghai. 77.17% of the dentists were young and middle aged, 47.85% of them had primary professional tiles, 42.23% of them had university educational background and the specialty of 68.04% of the dentists was general dentistry. 66.88% of the nurses had primary professional tiles and 68.45% of the nurses' educational background was below the junior college degree. The ratio of the dentists to nurses to technicians was 7:2:1. The public dental medical therapy units and dental manpower resources were concentrated in the downtown with 41.48% of the units, 68.23% of the dentists, 79.81% of the nurses and 82.21% of the technicians there. The total amount of dental out-patient departments (DOPDs) in public medical units in Shanghai in 2006 was 5,146,536, 69.23% in the downtown, with 26.95% in the tertiary hospitals. 15.79% of the units thought the DOPDs were too many while 56.23% considered just right. Among them, 27.20% of the units mostly in the downtown thought their units needed dentists. Among them, 66.67% of the units needed general dentists. CONCLUSIONS: Dental manpower in public medical units in Shanghai is not a small amount, but nurses are relatively in shortage. At the same time, its composition and distribution are not reasonable with the public dental manpower concentrating in the downtown and tertiary hospitals. Most of the patients visit the hospitals in the downtown and tertiary hospitals for treatment. PMID- 20300690 TI - [A study of oral health behaviors among 65 to 74 years old people in Shanxi province]. AB - PURPOSE: To assess the oral health behaviors among 65 to 74 years old people in Shanxi province, and provide a base line for oral health service. METHODS: Four hundred and five old people aged from 65 to 74 in Shaanxi province was selected according to the Third National Oral Health Investigation Criteria and the oral health behaviors of them were investigated by questionnaire. SPSS 13.0 software package was used for statistical analysis. RESULTS: Of the participates, 14.3%, 6.6%, 39.5% of old people ate dessert, candy/chocolate, sugar-containing dairy products every day, and 27.5%, 17.0%, 0.7%, 0.5% drank fresh fruit, saccharine, fruit juice, carbonated drinks once daily, respectively. Compared with the rural areas,the proportion of people who drank fresh fruit or ate dessert, sugar containing dairy products once daily was higher in the urban area (P<0.01). The proportion of people who significantly smoked cigarette, drank alcohol, or drank tea every day was 31.4%, 33.8% and 70.6%, respectively. Smoking and tea consumption were more prevalent in the urban area as well as in males(P<0.01). No difference was found between the prevalence of drinking alcohol in the urban and rural area(P>0.05), but more males drank alcohol than females(P<0.01). 55.8% of people brushed their teeth more than one time a day. Among the investigated people, about 80% never used the toothpick;only 0.7% of them used dental floss;About 30% of the investigated people used fluorine-contained toothpaste, more of them in the urban areas (P<0.01). Fluorine toothpaste usage was 29.1%, significant difference was found between in the urban and rural area (P<0.01), but no significant difference was noted between in males and females(P>0.05). CONCLUSION: Oral health behaviors of 65 to 74 years old people in Shanxi province is irrationality, and needs to be adjusted and improved. PMID- 20300691 TI - [A survey on the need of oral treatment on residents in quake-hit areas in Dujiangyan city]. AB - PURPOSE: To survey the need of oral treatment, and to search the regularity of oral diseases occurrence among residents in quake-hit areas in Dujiangyan city. METHODS: Data of 970 residents had been collected from 15 sampling spots by the household oral health interview survey in Dujingyan city.The information was analyzed with FoxPro6.0 and SPSS11.5 software package. According to medical evacuation support,the need of oral treatment was classified into four degrees. RESULTS: The results showed that 3.8% of residents needed no oral treatment, 81.3% needed regular oral treatment, 62.8% needed early oral treatment, and 6.1% needed dental emergencies. CONCLUSIONS: The need of oral treatment in residents is very frequent and general in quake-hit areas. It's suggested that the work of oral health care is to be strengthened, and the order of oral health care is to be established. PMID- 20300692 TI - [A preliminary analysis of the ratio between the upper and lower anterior teeth]. AB - PURPOSE: The widths of anterior teeth are measured and compared to see if there was any specific ratio between the anterior teeth, and to provide some referential data for clinical application in esthetic dentistry. METHODS: Gypsum casts of the maxillary and mandibular arches were made by traditional ways. With the help of dividers and vernier calipers, the widths of anterior teeth were measured. The mean values were gained by doing the measurement several times. SAS6.12 software package was used for grouped t test, paired t test and REG regression. RESULTS: Statistically significant difference(P<0.01) was observed, when comparing the widths of anterior teeth with their ideal golden section(0.618 or 1.618). There were statistically significant differences in the correlation coefficient of anterior teeth(P=0.0001). CONCLUSIONS: The golden section is not found in the anterior teeth. There is some proportional relationships between the upper and lower anterior teeth. PMID- 20300693 TI - [Clinical efficacy of carbarnide peroxide in-home tooth whitening for removal of stains caused by dental fluorosis]. AB - PURPOSE: To evaluate the clinical efficacy of carbarnide peroxide in-home tooth whitening for removal of stains caused by dental fluorosis. METHODS: One hundred and eight teeth,from 24 patients with diffuse opacities on the enamel surfaces due to effects of dental fluorosis, were assigned into mild, medium and heavy groups, and treated with carbarnide peroxide in-home tooth whitening. Before, immediately after bleaching and one year later, CMYK shade guide was used to record the change of color. Bleaching efficacy and course of treatment were calculated, and lightening stability was evaluated. The sensitivity of teeth was recorded during the treatment by Visual analogue scale (VAS).The results were analyzed with SPSS13.0 software package for X(2) text. RESULTS: (1)Mild group had 100% decoloring efficacy after one course. The decoloring efficacy in medium and heavy groups was 94.29% and 86.21%. There was no significant difference among three groups(P>0.05).(2)There was no significant difference on the treatment efficacy between the time of treatment completion and after one year in all three groups(P>0.05).(3) The tooth sensitivity appeared during the treatment and disappeared in 2 to 3 hours after divorced from medicine. The sensitive rate was 56.52%. CONCLUSION: The bleaching efficacy of carbarnide peroxide in-home tooth whitening on dental fluorosis's stains is good, safe and can maintain a period of time. PMID- 20300694 TI - [Effect of enamel matrix proteins on the growth of apatite coating on chemically modified titanium]. AB - PURPOSE: To evaluate the effects of enamel matrix proteins(EMPs) on the growth of apatite coatings on dual thermo-etching or alkali heat-treated pure titanium(Ti). METHODS: EMPs were extracted from porcine tooth germs and identified by SDS-PAGE. Dual thermo-etching treated or alkali-heat treated Ti samples, then, were exposed in a blank or EMPs containing(150microg/mL) modified simulated body fluid(m-SBF) at 37degrees centigrade for 7 days. SEM, EDS, XRD and FTIR were employed to observe or analyze the morphologies, element components and crystal structures of the apatite coatings. RESULTS: In dual thermo-etching-treated groups, almost no calcium-phosphate deposits were found on the titanium surfaces of control group and some amount of calcium-phosphate deposits with the main element components of Ca, P, O and C, however, formed on those of experimental group. But in alkali heat-treated groups, the apatite coatings proved to be carbonate hydroxyapatite formed on the titanium surfaces of both control group and experimental group, and the apatite coatings of the latter were found porous(300-600nm) and uneven. CONCLUSIONS: Alkali heat-treatment is in favor of apatite deposition, and EMPs can promote apatite deposition on both dual thermo-etching and alkali heat treated pure titanium surfaces. PMID- 20300695 TI - [Establishment of xenografted model of oral verrucous carcinoma with focal squamous cell carcinoma metastasizing to the cervical lymph nodes in nude mice]. AB - PURPOSE: To use the excised cervical lymph node tissue from oral verrucous carcinoma patient with focal squamous cell carcinoma subcutaneously to establish a xenografted model in nude mice. METHODS: The xenograft tumors were finally removed for histopathological study and the mice were laparotomized to examine metastatic tumors in livers, kidneys, lungs. RESULTS: The tumor formation rate was 87.5%(7/8),and the appearance of transplanted tumors was like that in human and HE staining showed that the cancer cells of those tumors models and mesenchymal components remained morphologically like the original tumor. The liver, renal, lung and lymph nodes didn't show obvious metastasis. CONCLUSION: The xenografted model is successfully established with a higher formation rate, and the model morphologically resembles the human tumor. PMID- 20300696 TI - [Establishment and evaluation of the in vitro dynamic biofilm model]. AB - PURPOSE: To establish a dynamic model which could simulate the ecologic environment of oral cavity and study the cariogenicity of oral biofilm, continuously observe the formation of oral biofilm. METHODS: The fermental vessel and chemostat were designed according to the purpose of the study. Four strains of oral bacteria, namely Streptococcus mutans, Streptococcus sanguis, Lactobacillus rhamnosus and Actinomyces naeslundii, were inoculated in the fermenter. The hydroxyapatite (HA) discs and glass slides were put in the chemostat. The temperature, oxide pressure, pH, dilution rate, circulation rate and substrate of the chemostat were carefully modulated. Distilled water and 25mM sucrose solution were used to test the stability of the system. At the beginning of the model establishment, the anabiosis bacteria were inoculated in fermenter full of fresh artificial saliva with a dilution rate of 10%. After the growth of bacteria in the fermenter was stable, the four-organism bacterial consortium was inoculated in the chemotat for 24 hours together with fresh artificial saliva (v/v=1:9). The organisms in planktonic phase were examined everyday. When the populations of consortium got stable(about 72 hours), the test solution was pulsed in the chemostat every 12 hours for 5 days. The HA discs and glass slides were observed every 24 hours for five times. The data was analyzed using SPSS 10.0 software package. Dunnet t test was used to compare the difference between the two groups at the level of alpha=0.05. RESULTS: The dynamic model was successfully established on oral biofilm study. With the pulse of sucrose solution, the environment in the chemostat simulated the cariogenic environment in nature, and all data namely the bacteria population, the biofilm microstructure changed with solution pulse. CONCLSUIONS: The model established is proved to be stable and the parameters in the model could be successfully controlled. The model fulfills the dynamic observation of formation of biofilm and caries lesion in vitro. PMID- 20300697 TI - [Role of NF-kappaB pathway in shikonin induced apoptosis in oral squamous cell carcinoma Tca-8113 cells]. AB - PURPOSE: To investigate the role of NF-kappaB signal transduction pathway in apoptosis induced by shikonin in human tongue squamous cell carcinoma Tca-8113 cell line. METHODS: Expression of IkappaBa, phosphatase-IkappaBa, bcl-2 and Bax proteins were detected by Western blot, NF-kappaB DNA-binding activity was detected by electrophoretic mobility shift analysis (EMSA), and activities of caspase 3, caspase 8 and caspase 9 were analyzed by enzyme linked immunosorbent assay(ELISA). The data was analyzed by one-way ANOVA test and t test using SPSS12.0 software package. RESULTS: The expression of phosphatase-IkappaBa protein and the nuclear NF-kappaB DNA-binding activity was significantly decreased in shikonin treated cells by Western and EMSA. Bcl-2 protein expression was also decreased in the process. The activity of all the three proteases was elevated and pancaspase inhibitor Z-Asp-CH2-DCB could protect Tca8113 cells from shikonin-induced apoptosis(P=0.02). CONCLUSIONS: Anti-tumor effects of shikonin in Tca-8113 cells act at least partially through the inactivation of NF-kappaB pathway and subsequent activation of protease caspase family. Pharmacologic inhibition of the NF-kappaB activity by shikonin might be a powerful treatment option for OSCC. PMID- 20300699 TI - [A pilot study of three dimensional printing of human bone marrow stem cells (hBMSCs)]. AB - PURPOSE: To establish a three-dimensional biological printing technique of hBMSCs. METHODS: The hBMSCs were regularly isolated and cultured, and adjusted to the density of 1x10(6)/mL single cell suspension. Then these cells were labeled by PI fluorescence marker, and transferred by rapid prototype biological printer. Deposition spots were 300microm apart at X-axis, 500microm at Y-axis, 50microm at Z-axis, and then observed by laser confocal microscope. RESULTS: This technique could deposit cells with good spatial control. In three-dimensional layer, each "cell ink" drop contained 15-35 hBMSCs post-transfer, and achieved accurate distribution with spots distributed 300microm apart at x-axis, 500microm at y axis and 50microm at Z-axis. CONCLUSIONS: This study indicates that hBMSCs can be effectively delivered by a rapid prototype printer with speed and accuracy. Application of three dimensional printing is of great importance in tissue engineering bone. PMID- 20300698 TI - [Study on cytotoxicity of three kinds of dental ceramic alloys on L929 mouse fibroblasts in vitro]. AB - PURPOSE: To investigate the cytotoxicity in vitro of three kinds of dental ceramic alloys on L929 mouse fibroblasts. METHODS: CCK-8 assay was a quick method to study the cell relative proliferation rate or cytotoxicity. L929 mouse fibroblasts were used to detect the cell relative proliferation rate of the three kinds of dental ceramic alloys(NiCr,CoCr and golden alloys containing 58% of gold) by CCK-8 assay. The DNA damage of L929 mouse fibroblasts was determined by single cell gel electrophoresis(SCGE). The data was statistically analyzed with SAS 9.0 software package. RESULTS: The relative growth rate induced by NiCr, CoCr and golden dental ceramic alloys was (75.9510+/-7.6244)%, (84.8920+/-8.2660)% and (88.5420+/-12.3611)%, respectively. NiCr ceramic alloys caused the most marked cytotoxicity(P<0.05), and there was no difference between CoCr ceramic alloys and 58% golden ceramic alloys(P>0.05). The cytotoxicity of the three kinds of metal ceramic alloys was all grade 1, i.e. mild cytotoxicity. The DNA damage of L929 mouse fibroblasts induced by NiCr ceramic alloys was most serious(P<0.05). There was no difference in the DNA damage between CoCr ceramic alloys and 58% golden ceramic alloys(P>0.05). CONCLUSIONS: NiCr ceramic alloys can suppress the proliferation of the L929 mouse fibroblasts and promote DNA damage. While CoCr ceramic alloys which are similar to 58% golden ceramic alloys show less cytotoxicity than NiCr ceramic alloys. CoCr or 58% golden ceramic alloys should be used as crown and bridge for patients instead of NiCr ceramic alloy clinically. PMID- 20300700 TI - [Nifedipine regulated expression of bcl-2 in human gingival epithelial cells in vitro]. AB - PURPOSE: To investigate the effect of nifedipine(NIF) on transcription of bcl-2 in human gingival epithelial cells(HGECs) in vitro and to study the pathogenesis of epithelial thickening in drug-induced gingival overgrowth(DGO). METHODS: The gingival tissues obtained from periodontal surgeries were digested with enzyme and HGECs were cultured in vitro; HGECs were identified by immunohistochemistry; bcl-2 mRNA levels were quantitated by Real-time PCR 24 hours and 48 hours after cells stimulated by NIF with different concentration (0microg/ml, 1microg/ml,2microg/ml,3microg/ml), in which 0microg/ml NIF as blank control. The data was analyzed by one-way ANOVA using SPSS 11.0 software package. RESULTS: HGECs cultured in vitro showed keratin positive signal and vimentin negative signal; the level of bcl-2 mRNA increased with NIF 3microg/ml after 24 hours treatment, which appeared significant increase compared with blank control (P<0.05); after 48 hours treatment the level of bcl-2 mRNA in the groups of 2microg/ml and 3microg/ml showed significant increase compared with blank control (P<0.05). CONCLUSION: NIF regulates the level of bcl-2 mRNA. PMID- 20300701 TI - [Morphological and histological adaptation after mandibular functional positioning only in vertical dimension]. AB - PURPOSE: To elucidate the role of mandibular vertical functional positioning in condylar adaptive remodeling. METHODS: Forty female Sprague-Dawley rats at the age of 5 weeks were randomly divided into 4 control and experimental groups. All the animals were sacrificed on day 3, 6, 9 and 12 (n=5). Bite plates on upper posterior teeth were fitted on the experimental animals to induce functional repositioning of the mandible. Morphological and histological analysis was carried out to quantitatively analyze the amount of the adaptive changes of condylar cartilage. Independent-samples t test and One-Way ANOVA using SPSS11.0 software package were performed. RESULTS: Twelve days after mandibular vertical functional positioning the condylar height increased. Nine days after mandibular vertical functional positioning the thickness of prechondroblast layer and chondroblast layer increased significantly compared with control groups. However the thickness of hypertrophic layer decreased significantly after 6 days' mandibular repositioning. No change was found in the thickness of mesenchymal layer during the experimental period. CONCLUSIONS: Mandibular vertical functional positioning could enhance the growth of condyle. The resulted adaptive remodeling in condylar cartilage plays an important role in the treatment mechanism of mandibular deficiency via functional appliances. PMID- 20300702 TI - [Observation of the number of molar root canal with X-ray imaging and three dimensional imaging]. AB - PURPOSE: To find a convenient way to reconstruct the morphologic characters of the molar root canal with 3dsmax8.0 software in the laboratory and evaluate the difference of the number of molar root canal between the in vivo X-ray image and three-dimensional image. METHODS: Twelve recently extracted molar roots were studied. In vivo X-ray images were taken before serial section. Starting at the root apex, serial cross sections were taken from each specimen using a saw microtome, and each cross section was photographed under a stereoscopic microscope. All of the digital photos were inputted into the computer to be reconstructed by 3dsmax software. RESULTS: A three-dimensional image of the molar root canal was built successfully. There were 19 molar root canals observed via in vivo X-ray image and 47 molar root canals observed in the three-dimensional image. The number of molar root canal that observed via in vivo X-ray image was less than that from the three-dimensional image. CONCLUSION: Use of saw microtome and 3dsmax software can reconstruct the three-dimensional image of the tooth. PMID- 20300703 TI - [The establishment of three dimensional finite element model of a maxillary impacted canine and its support tissues]. AB - PURPOSE: To establish a three dimensional finite element model of a maxillary impacted canine and its support tissues by means of finite element method (FEM) and spiral CT which can offer digital model for orthodontic traction. METHODS: A patient with a completely bony impacted maxillary canine was chosen. The CAD model of the canine and its surrounding tissues was established using spiral CT equipment, Mimics and Unigraphic. The CAD model was changed to FEM models by MSC. Mentat which could cut nets in CAD models. RESULTS: With the use of spiral CT,Mimics,UG and MSC, FEM model of the maxillary impacted canine and its support tissues and the whole maxilla was constructed and the model was of high geometrical similarity. CONCLUSION: The FEM model of maxillary impacted canine established by spiral CT,Mimics,UG and MSC has high accuracy, integrated constitution and optimized mesh which can be taken into account in the course of the treatment planning prior to starting therapy. PMID- 20300704 TI - [Comparative study on the shaping ability of canals with 2 new nickel- titanium rotary instruments]. AB - PURPOSE: To compare the shaping ability of two nickel-titanium rotary systems: Mtwo and K3. METHODS: Thirty-six mesio-buccal root canals of maxillary first molars were divided into two groups: group A(> or =20> or =) and group B(<20 degrees ),according to the angle of the canal. Then, each group was randomly divided into two subsets and prepared by Mtwo,K3, respectively. All root canals were injected with the contrast medium and digital images of all canals were recorded before and after instrumentation. The computer assistant analyze image software was used to form the geometrical central line of pre-instrumented canals. Then the central line was imaged to the post-instrumented canals. The canal transportation and the decrease of curvature were measured. All the data was analyzed with SPSS11.0 software package. RESULTS: Difference between groups was compared using t test.When the curvature of canal > or =20 degrees ,the transportation at the beginning of the curvature and the decrease of curvature of Mtwo were significantly less than those of K3(P<0.05).When the curvature of canal <20 degrees there was no significant difference between Mtwo and K3 in the transportation and decrease of curvature(P>0.05). CONCLUSIONS: Both Mtwo and K3 systems show good preservation of the original geometry of the root canals, the Mtwo system can better preserve original curvature of canals, when the curvature of canal is larger than 20 degrees . PMID- 20300705 TI - [The influence of temperature and curing light units on the microhardness of composite resin]. AB - PURPOSE: To investigate the effect of different temperature and different light curing units on the hardness of composite resin. METHODS: Specimens were fabricated from Clearfil AP-X composite resin (Kuraray,Japan)and stored at three different temperature(5degrees centigrade,23degrees centigrade,40degrees centigrade).Then they were cured by a quartz tungsten halogen Translux CL or a second generation LED Elipar FreeLight2. The microhardness of the top and bottom surfaces of the specimens were determined using a digital microhardness tester. Statistical analyses were performed using the two-way ANOVA by SPSS 17.0 software package. RESULTS: Whether cured by QTH or LED, the specimens stored at 40degrees centigrade had higher top and bottom hardness value than that stored at the other temperatures(P<0.01). The LED light produced a significantly better hardness on top and bottom surfaces of specimens stored at the three different temperatures(P<0.01). CONCLUSIONS: The use of pre-warmed composite resins might help to increase the composite resin hardness. Second generation LED is more efficient than halogen light unit. PMID- 20300706 TI - [Bilingual teaching in stomatological education in China: problems and future strategies]. AB - Bilingual teaching has been used for several years in many Colleges of Stomatology in China, but there are still some problems be solved in textbooks, training of teachers, methods of teaching, etc. This paper discusses the purpose, manners, problems and strategies of bilingual teaching in stomatology. We believe that the specialties of stomatology and the situations of China should be considered in conducting bilingual teaching. The purposes of bilingual teaching are to use English and/or Chinese to teach basic and clinical knowledge and skill in Stomatology, and enhance the English ability of the students as well. To achieve the purposes and improve the quality of bilingual teaching, a well organized textbook and adequate qualified teachers are demanded, modern teaching medias and methods should be adopted, and a rational teaching quality evaluation system should be established and fulfilled. PMID- 20300707 TI - [A mandibular second molar with three mesial roots: report of one case]. AB - A case of unusual root canal morphology was presented to demonstrate anatomic variations in mandibular second molars. This case report presented the endodontic therapy of a mandibular second molar with three canals in the mesial root. A mesial middle canal was found between the mesiobuccal and mesiolingual canals. This report indicated the importance of looking for additional canals and unusual canal morphology, because knowledge of their existence might occasionally enable clinicians to treat a case successfully that otherwise to fail. PMID- 20300708 TI - [Circadian rhythmicity and addiction]. AB - The chronobiological aspects of addiction constitute a recently developed field of study that has obtained interesting data from both basic and clinical research. Drug consumption has a negative effect on the expression of circadian rhythmicity, since it produces a flattening of the functions and a delay of maximal values, and can even cause a state of desynchronization of endogenous control. Moreover, it has been shown that the clock-genes Clock and Per2 are associated with vulnerability to addiction, the first gene directly regulating dopaminergic activity in the reward system and the second participating in the sensitivity to and abstinence from drugs. The evening circadian typology has also been proposed as an individual difference to be taken into account as a risk factor in the development of drug addiction. Finally, the reorganization of circadian rhythmicity with regular daily schedules adjusted to the cycle of light darkness, exposure to natural or artificial light, and the administration of melatonin may be useful strategies in the treatment of drug addictions. PMID- 20300709 TI - [Prevention of substance abuse: randomised or observational evaluation is absolutely needed]. AB - Prevention programs and interventions in the field of drug abuse are designed to reduce the incidence of onset of substance use, but they can also produce harms. This is the reason why rigorous evaluations are absolutely needed. In Europe, in spite of the large spread of such interventions, they are rarely evaluated with rigorous study designs. For these reasons it is important to promote the evaluation of every program that can be considered of relevance. This would allow the other practitioners to choose the interventions on the base of evidence of effectiveness. But which kind of evaluation prevention programs needed? There is a substantial agreement on the role of the randomized evaluation. Randomization is the only effective way to control for numerous factors that can bias the results. The typical evaluation design associated to most part of intervention programs, the pre-post assessment, cannot produce unbiased estimations. There are however many interventions that cannot be randomised, because they cannot be provided at the individual level (e.g like the price policies for cigarettes). These programs require an observational approach for evaluation, like a cohort or an Interrupted Time Series design. Even if these study designs have a complex methodology, the evaluation is of high relevance in order to allow the development of prevention strategies based on evidence. PMID- 20300710 TI - [Research on etiological aspects of dual pathology]. AB - INTRODUCTION: It is important to assess the interaction between family psychopathologic history (FH), family dynamics (FD), behavior disorders, substance-use disorders and personality disorders (PD). METHODOLOGY: Cross sectional design. The sample was made up of 350 subjects with substance-use disorders who were assessed for FH including alcoholism and substance-use disorders through an interview; for substance use via a questionnaire; for FD; for PD using the International Personality Disorder Examination (IPDE); for behavior problems in adolescence; and for disocial disorder. Correlated variables were included in logistic regression models. RESULTS: Early age of onset for substance use is related to FH of substance use disorders and poorer FD. FH of alcoholism, substance-use disorders and psychiatric disorders are related to poorer FD. Early age of onset for substance use, FH and a disruptive FD are related to behavior problems and disocial disorder. Early age of onset for substance use, FH, disruptive FD, behavior problems and disocial disorder are related to presence of PD. Logistic regression predicted the presence of PD by age of onset for use of methadone (CI(95):1.005/3.222; p=0.048) and of other opiates (CI(95):0.864/0.992;p=0.028). FH score in alcoholism predicted Borderline Personality Disorder (CI(95):1.137- 2.942; p=0.013), and age of onset of cocaine use predicted Antisocial Personality Disorder (CI(95):0.864/0.992; p=0.028). CONCLUSIONS: FH of substance use and own use predict the presence of some PDs. PMID- 20300711 TI - [Myocardial necrosis and severe biventricular dysfunction in the context of chronic ephedrine abuse]. AB - Ephedra is an amphetamine-like compound with a potent sympathomimetic effect. Ephedrine, its active component, is widely used for weight loss, to enhance athletic performance or as component of some drugs. Its cardiovascular effects include tachycardia, increased inotropy, arterial vasoconstriction and hypertension, and these are the effects for which it is used therapeutically. However, it can also cause adverse effects, such as neuropathy, myopathy, psychosis, addiction, stroke, insomnia, myocarditis, arrhythmias, myocardial infarction or sudden death. We present the case of a patient, with pre-existing psychiatric conditions, who developed congestive heart failure and pulmonary oedema in the context of severe biventricular dysfunction and myocardial necrosis secondary to longstanding ephedrine abuse. Secondary causes of dilated myocardiopathy such as alcohol abuse, autoimmunity, hemochromatosis, thyroid alterations, viral or bacterial myocarditis and coronary heart disease, were ruled out. Five years after total cessation of use of the drug containing ephedrine, the patient is symptom-free, with partial recovery of left ventricular ejection fraction. PMID- 20300712 TI - [Validity of the Spanish version of the Hypersensitive Narcissism Scale (HSNS) in subjects attended at an Addiction Treatment Unit]. AB - INTRODUCTION: Narcissistic personality is an important component of personality disorders which are prevalent in those presenting drug abuse or dependence. Assessment instruments usually consider self-esteem, narcissism and covert narcissism, but although Spanish versions of instruments for self-esteem and narcissism are available, there is no available test for covert narcissism. OBJECTIVE. To test the validity of the Spanish version of the Hypersensitive Narcissism Scale (HSNS) in individuals presenting drug abuse or dependence. METHOD: In a sample of 79 outpatients, we assessed reliability by means of Cronbach's alpha and the intraclass correlation coefficient (ICC), construct validity through factor analysis, and concurrent validity by means of the correlation between the HSNS and measures of severity, disability, self-esteem, grandiose narcissism and personality disorders. RESULTS: Reliability of the HSNS total scale score was satisfactory (Cronbach's alpha = 0,73, ICC = 0,67), though some items would require further consideration. Factor analysis showed good construct validity with three factors compatible with the theory of covert narcissism. With regard to concurrent validity, covert narcissism (HSNS) correlated positively with open narcissism, severity and disability due to drug use, and negatively with self-esteem. Highest scores on the HSNS corresponded to borderline, narcissistic and passive-aggressive personality disorders. CONCLUSIONS: The Spanish version of the HSNS could be a valid instrument for the assessment of covert narcissism in those treated for drug abuse or dependence. PMID- 20300713 TI - [Psychometric properties of the Nicotine Dependence Syndrome Scale (NDSS) in a sample of smokers treated for their alcohol dependence]. AB - The assessment of nicotine dependence with brief instruments is of great relevance for the better detection of this disorder. Here we present the results with the Nicotine Dependence Syndrome Scale (NDSS) by Shiffman, Waters and Hickcox (2004) in a sample of 183 patients treated at an Alcohol Dependence Unit who were also cigarette smokers. The results indicate that the general factor which evaluates nicotine dependence (NDSS-T) has good reliability (Cronbach's alpha = 0.80). Factor analysis identifies four of the five factors proposed in the original version, those of drive, priority, continuity and stereotypy. Reliability of the scales derived ranges from very good (0.80) to moderate (0.63). The NDSS-T correlates significantly with the Fagerstrom Tolerance Questionnaire (FTQ), with the DSM-IV criteria for nicotine dependence assessed through the SCID, and with the number of cigarettes smoked per day. The ROC curves indicate an NDSS-T score of 0.80 under the curve (0.70 for the FTND), showing that it adequately predicts nicotine dependence. This study confirms the utility of this new instrument for assessing nicotine dependence in smokers who also abuse or depend upon alcohol. PMID- 20300714 TI - [Relationship between cocaine dependence treatment and personal values of openness to change and conservation]. AB - OBJECTIVE: To analyze the relationship between participation in a drug addiction treatment program and Schwartz's values of Openness to change (Self-direction, Stimulation and Hedonism) and Conservation (Tradition, Conformity and Security) in cocaine users. METHOD: The present quasi-experimental study was carried out on a sample of 411 adult cocaine users, grouped according to whether they had begun treatment more than three months earlier or less than three months earlier or they were not receiving any treatment. Using Schwartz's Personal Values Questionnaire (PVQ), we measured the priority given by each of these groups to the values of Conservation and Openness to change. RESULTS: Participants who had initiated the treatment more than three months earlier tended to score lower in the values of Openness to change than those who were not in treatment, though there were no significant differences in these values between those who were not in treatment and those who had been in treatment for less than three months. On the other hand, it was observed that participants in treatment, regardless of the time spent in treatment, scored higher in values of Conservation than the cocaine users who were not in treatment. DISCUSSION: These results reveal the relationship between attendance on a cocaine-dependence treatment program and personal values, together with their potential importance in treatment and rehabilitation programs for cocaine users. PMID- 20300715 TI - [Treatment dropout in cocaine addicts]. AB - The high rate of dropout from treatment programs is one of the most serious problems in the field of drug dependence. Early identification of predictors of dropout risk can provide useful information on the specific treatment needs of these types of patient. The aim of this study was to identify predictors of premature cessation of an outpatient treatment program for cocaine addicts. The study was carried out at public healthcare units in a Spanish city. Participants were 91 cocaine addicts admitted for treatment for their addiction, assessed by means of interview and various self-report measures. For identifying predictive variables the researchers used a factor analysis, a cluster analysis and a CHAID analysis. The variables that obtained predictive capacity were the MAST scores and the combined alcohol and drugs scores on the EuropASI. These three variables were grouped in a single factor which was called addictive severity. The predictive analysis showed that this factor had some degree of capacity for the prediction of dropout, but that it was not completely determinant. The results suggest the advantage of detecting at the admission stage those patients who might require more attention to their motivational aspects, greater treatment control and intensity, or the provision of complementary interventions. PMID- 20300716 TI - [Psychometric properties of the GHQ-28 in opiate-dependent patients]. AB - OBJECTIVE: To know the psychometric properties of the GHQ-28 when it is applied to a sample of opiate-dependent patients. METHOD: Participants were 138 opiate dependent patients. Reliability was estimated by means of the Cronbach's alpha and Spearman-Brown coefficients. Confirmatory Factor Analysis was applied to check the four-factor structure proposed by Goldberg and Hillier. The sensitivity and specificity of the instrument for the detection of possible psychiatric cases were measured using ROC (Receiver Operating Characteristic) analysis, using as criterion the DSMIV diagnosis from the Mini International Neuropsychiatric Interview. RESULTS: Reliability estimation was adequate. Validity results could not confirm the four-factor structure of GHQ-28 proposed by Goldberg and Hillier. The sensitivity and specificity parameters show optimum values of 60.7 % and 73.7 %, respectively, 65.9 % of the participants being correctly classified. CONCLUSIONS: GHQ-28 shows adequate reliability and appropriate sensitivity and specificity parameters when it is applied to opiate-dependent patients. However, the original factorial structure could not be confirmed. Given these results and those from other validity studies in which the relationships with Severity of Dependence, Physical Health and Health-Related Quality of Life were shown, the GHQ-28 can be considered a useful instrument for screening in clinical practice. PMID- 20300717 TI - [Delay in seeking medical care in patients addicted to psychoactive substances]. AB - INTRODUCTION: Clinical practice shows that addict patients tend to seek attention from health services after a long period of time, and that their relatives do not seek early medical care, despite knowledge of the addiction. OBJECTIVES: To determine the time elapsed between the beginning of patients' substance use and when they first seek specialized medical care (TC) and the time elapsed between relatives perceiving the substance use and when they first seek specialized medical care (TSAM); also, to identify the factors associated with seeking medical care earlier. DESIGN: Observational, descriptive study. A structured survey, validated by experts in the field of addiction, was applied to 113 family members responsible for patients addicted to psychoactive substances in 5 hospitals in the city of Lima. RESULTS: Patients seek specialist medical care for the first time 11.22 years after commencement of substance use, and family members take to 4.69 years to seek medical care from when they perceive of the substance use. Female gender, the concept of addiction as a disease and not waiting for the patient's decision before seeking medical care reduce TC and TSAM in the case of most substances. CONCLUSIONS: Patients addicted to psychoactive substances turn to health services only after long TC and TSAM; moreover, the delay in seeking medical care on the part of relatives means that patients continue to use substances. PMID- 20300718 TI - [The promotion of resilience and protective factors in children of alcoholics and drug addicts]. AB - Children from families of alcoholics and drug addicts are a high-risk group for developing a mental or substance-related disorder. The parental substance-related disorder can cause different effects on the physical, mental, and cognitive health of children in various stages of development, particularly internalizing and externalizing disorders. For the development of the mental health of these children, the promotion of resilience and protective factors play a crucial role. General and specific resilience and protective factors, which are relevant for prevention and intervention for children of alcoholics and substance users, are presented based on empirical studies. Resilience is commonly understood as a mental hardiness of children and adolescents to biological, mental, and psychosocial developmental risks. Important is the multilevel consideration of internal and external protective factors. In doing so, resilience is understood as a process that is subject to fluctuations over the course of life. The "stress strain-coping-support" model is suitable for the theoretical concept of preventive measures for children of alcoholics and drug addicts. PMID- 20300719 TI - [Requirements for hygiene in the medical care of immunocompromised patients. Recommendations from the Committee for Hospital Hygiene and Infection Prevention at the Robert Koch Institute (RKI)]. PMID- 20300721 TI - [Langerhans cell histiocytosis. Solitary facial lesion]. AB - Langerhans cell histiocytosis is the general term for all clinical entities characterized by a proliferation of dendritic cells that are phenotypically identical to the Langerhans cells of the skin. As dendritic cells are present in nearly every tissue of the body, Langerhans cell histiocytosis shows a broad spectrum of clinical manifestations, mostly in the bone (approximately 80%) and skin (approximately 60%). Langerhans cell histiocytosis is basically a disease of the childhood and early youth, but can rarely occur in the elderly. Here, we report on a 70-year-old man presenting with a single facial lesion of Langerhans cell histiocytosis and summarize the most important clinical aspects as well as current therapeutic concepts. PMID- 20300720 TI - [Infantile hemangioma. Successful treatment with propranolol]. AB - We report on an infant, aged four months, suffering from a severe hemangioma of the left labium majus. We induced systemic treatment with propranolol in off label-use over a period of 5 1/2 months. A few weeks after onset of the treatment, the size and color of hemangioma was obviously reduced; finally there was an almost complete regression. This result underlines the role of propranolol in treatment of problematic hemangioma. PMID- 20300722 TI - [Classical and atypical presentations of Galli-Galli disease]. AB - Galli-Galli disease is a rare genodermatosis which classically presents with reticulate hyperpigmentation of the flexures and intertriginous areas. Recently, an atypical clinical presentation of Galli-Galli disease with monomorphic lentigo like maculae and papules has been reported. We describe two cases of Galli-Galli disease, one patient presenting with a classical form and another with atypical skin lesions. In spite of the clinical differences, the histopathological examination - with filiform elongated rete ridges and acantholysis - confirmed the diagnosis of Galli-Galli disease in both cases. PMID- 20300723 TI - [Metastatic Crohn disease. Atypical manifestation]. AB - Crohn disease may be associated with many different typical and atypical cutaneous manifestations, also known as "metastatic Crohn disease". A 33-year-old man presented with generalized erythematous plaques with bullae and pustules. Histological examination revealed dense epidermal and dermal neutrophilic infiltration, as well as dermal edema with signs of vasculitis. The patient recovered with topical and systemic glucocorticosteroids. The lesions healed with both flat and hypertrophic scars. In summary, we present a generalized atypical case of metastatic Crohn disease. PMID- 20300724 TI - [International Classification of Function, Disability and Health (ICF). Basis for cutaneous rehabilitation management]. AB - Functioning and health are central issues in medical rehabilitation. With the International Classification of Functioning, Disability and Health (ICF), the World Health Organization implemented in 2001 a system for the description and classification of functioning that is accepted worldwide. Applying the bio-psycho social perspective, this model based on interdependencies, comprises the components Body Function, Body Structure and Activity and Participation as well as contextual influences of health: the Environmental and Personal factors. The ICF is of prime importance in clinical practice, teaching, and research. It provides a universal language to be used in health care permitting the characterization of the specific functional problems of individuals. The rehabilitation of skin diseases takes advantage on the ICF in rehabilitation management. In this paper we describe the philosophy of the ICF and its implementation in rehabilitation of patients with chronic skin problems on the basis of a case study. PMID- 20300725 TI - Vascular calcification and magnesium. PMID- 20300726 TI - [Artificial sphincter for the treatment of incontinence]. AB - The artificial urinary sphincter (AUS) has been successfully implanted in the last 40 years. Continuous improvement of the AUS and increasing experience with the device has led to its widespread acceptance. The major indication is still post-prostatectomy incontinence. In this collective patient satisfaction was reported in over 90%. In a number of patients with neurogenic bladder dysfunction and congenital or acquired anatomical disorders of the urethra, an AUS can be an alternative to urinary diversion. Nonetheless, complications such as infections and erosions are still a problem, leading to revisions and secondary procedures in up to 20% of the cases. Therefore, operative expertise and precise execution of aseptic rules are basic prerequisites. PMID- 20300727 TI - Mental health services in the health accounts: the Czech Republic. AB - BACKGROUND: Policy makers as well as health services researchers lack information on financial flows within national mental health systems. The studies that are available use different methodologies and hence it is difficult to make any comparisons. The aim of this study was to modify the existing health accounting framework and apply it to describe and analyse the financial flows within a national mental health system. METHODS: Mental health expenditures are classified by the three-dimensional methodology of OECD health accounts that is extended by two other dimensions for the purpose of the study. RESULTS: The framework of five dimensional mental health accounts is introduced and applied to mental health expenditure in the Czech Republic, 2006. Mental health expenditure is estimated to be 4.14% of the total health expenditure. Mental health expenditure is classified based on its source of financing, provider industry, health-care function, cost category and diagnostic group. CONCLUSIONS: Health expenditure estimates present the most detailed information on resource allocation in the mental health system of the Czech Republic. The application of the standardized framework in other countries can improve the quality of international comparisons. On the national level, especially if the time series are available, mental health accounts can serve as a useful tool for strategic resource allocation decisions. This is particularly useful for the countries that plan changes in resource allocation directed from institutional to community-based care. PMID- 20300728 TI - Shortage and underutilization of psychiatric beds in southern Brazil: independent data of Brazilian mental health reform. AB - BACKGROUND: Mental health policies throughout the world are being subjected to several changes due to increased pressure from the public and from health administrators. Mental health policies in the developing world experienced changes following advice and consultation from the World Health Organization (WHO). This was the case with Brazil, which enacted several laws and policies affecting community care and the closure of beds in psychiatric hospitals (the deinstitutionalization movement). Rio Grande do Sul, the southeast state in Brazil, adopted this policy in 1992, but still suffers from a shortage of psychiatric beds in both general hospitals (GHs) and psychiatric hospitals (PHs), despite advances in the provision of community care. As a result, Rio Grande do Sul (RS) can be studied as an example of "what actually happens" in mental health care in the developing world. METHODS: The study analyzed online administrative data from 2000 to 2007 for three main parameters of mental health care (i.e. hospital use rate, length of stay, and hospital bed capacity). These were used to evaluate differences in psychiatric care among GHs and PHs. The number of existing and required psychiatric beds in RS was also calculated. RESULTS: GHs had very low hospital use rates, while PHs had a very high length of stay (200% higher than GH). The number of admissions to GHs grew by 170% over the 8 year period, and psychiatric bed availability was 1.5 per 10,000 inhabitants. CONCLUSIONS: The study provided evidence for the need of 30-50% more psychiatric beds in GHs. Also, additional staff training is needed to increase use rates in GHs and decrease the length of stay in PHs. Additional studies covering national data must be carried out to assess the extent of these problem in other Brazilian mental health care services. PMID- 20300730 TI - Effect of processing on dislodging of cypermethrin residues on brinjal. AB - Brinjal fruits were sprayed with recommended dose (0.001%) of cypermethrin. Effects of processing viz. washing, cooking in water, cooking in oil, microwave cooking, and grilling was studied to dislodge cypermethrin residues on brinjal. Cypermethrin residues remaining in the control and processed samples were analyzed by gas chromatography equipped with ECD. Dislodging of cypermethrin residues was observed more in grilling (50.12%), followed by cooking in oil (45.2%), cooking in water (41.4%), and microwave cooking (40.89%) after 1st day of the treatment. Reduction of residues after washing treatment was minimal. PMID- 20300729 TI - Social dynamics of postpartum depression: a population-based screening in South Eastern Hungary. AB - PURPOSE: To determine contributing psychosocial factors to postnatal depression (PND) in Hungary in 1996 and in 2006. METHODS: In 1996 and 2006, a total of 2,333 and 1,619 women, respectively, were screened for PND in South-Eastern Hungary, based on a Leverton questionnaire (LQ) score of >= 12 at 6-10 weeks after delivery. RESULTS: The LQ scores indicated an increase in PND from 15.0% in 1996 to 17.4% in 2006. The best predictors for PND in a multiple regression analysis were living in an urban environment [adjusted odds ratio (AOR) = 11.26], unstable relationship (AOR = 3.1) and a perceived lack of social support from partner (AOR = 3.65) in 1996, and recent major life events (AOR = 3.38), unstable relationship (AOR = 3.84), self-reported low income (AOR = 1.82), and intention to return to work soon after delivery (AOR = 0.47) in 2006. CONCLUSIONS: A self-defined low socioeconomic status and an intention to return to work have become significant factors in the development of PND. Besides the family factors recognized as salient variables in 1996, economic features came into prominence as newly identified main predictive factors for PND in 2006. PMID- 20300731 TI - Impact of simulation-based learning on medication error rates in critically ill patients. AB - PURPOSE: To compare medication administration error rates before and after the provision of educational sessions using either traditional didactic lecture or simulation-based training. METHODS: A single-center, parallel, controlled, prospective study conducted in adult coronary critical care (CCU) and medical intensive care units (MICU). Twenty-four nurses were observed administering medications. Documentation included drug name, dose, route, time and technique during observation and active medication orders in the patient's chart. A direct observation method was completed at baseline and repeated twice after the interventions. Data obtained during observation were analyzed for medication administration error rates. Interventions were two types of educational sessions with content developed from baseline medication administration error data: simulation-based training for CCU nurses and a didactic lecture for MICU nurses. Quizzes completed before and after the interventions were used to assess knowledge. RESULTS: A total of 880 doses (402 CCU, 478 MICU) were observed. After the simulation-based educational intervention in the CCU, medication administration error rates decreased from 30.8 to 4.0% (p < 0.001) in the initial post-intervention observation and were sustained in the final post-intervention observation (30.8 to 6.2%; p < 0.001). The error rate in the MICU after the didactic lecture intervention was not significantly different from the baseline and increased in the final post-intervention observation from 20.8 to 36.7% (p = 0.002). Mean quiz scores were significantly improved after education sessions in both ICUs. CONCLUSIONS: Simulation-based learning provides a significant advantage to patient care through the reduction of medication administration errors compared to lecture style education. PMID- 20300733 TI - The US FRAX filter: avoiding confusion or hindering progress? PMID- 20300732 TI - The relation between geometry and function of the ankle joint complex: a biomechanical review. AB - This review deals with the relation between the anatomy and function of the ankle joint complex. The questions addressed are how high do the forces in the ankle joint get, where can the joints go (range of motion) and where do they go during walking and running. Finally the role of the ligaments and the articular surfaces is discussed, i.e. how does it happen. The magnitude of the loads on the ankle joint complex are primarily determined by muscle activity and can be as high as four times the body weight during walking. For the maximal range of motion, plantar and dorsiflexion occurs in the talocrural joint and marginally at the subtalar joint. In-eversion takes place at both levels. The functional range of motion is well within the limits of the maximal range of motion. The ligaments do not contribute to the forces for the functional range of motion but determine the maximal range of motion together with the articular surfaces. The geometry of the articular surfaces primarily determines the kinematics. Clinical studies must include these anatomical aspects to better understand the mechanism of injury, recovery, and interventions. Models can elucidate the mechanism by which the anatomy relates to the function. The relation between the anatomy and mechanical properties of the joint structures and joint function should be considered for diagnosis and treatment of ankle joint pathology. PMID- 20300737 TI - Imaging methods for elemental, chemical, molecular, and morphological analyses of single cells. AB - Combining elemental, chemical, molecular, and morphological imaging information from individual cells with a lateral resolution well below 1 x 1 microm(2) is the current technological challenge for investigating the smallest dimensions of living systems. In the race for such analytical performance, several techniques have been successfully developed; some use probes to determine given cellular contents whereas others use possible interactions between cellular matter with light or elements for characterization of contents. Morphological techniques providing information about cell dimensions have, when combined with other techniques, also opened the way to quantitative studies. New analytical opportunities are now being considered in cell biology, combining top-performance imaging techniques, applied to the same biosystem, with microscopy (nm-mum range) techniques providing elemental (micro-X-ray fluorescence, particle-induced X-ray emission, secondary-ion mass spectrometry), chemical (Raman, coherent anti-stokes Raman, Fourier-transform infrared, and near-field), molecular (UV-visible confocal and multiphoton), and morphological (AFM, ellipsometry, X-ray phase contrast, digital holography) information. Dedicated cell-culture methods have been proposed for multimodal imaging in vitro and/or ex vivo. This review shows that in addition to UV-fluorescent techniques, the imaging modalities able to provide interesting information about a cell, with high spatial and time resolution, have grown sufficiently to envisage quantitative analysis of chemical species inside subcellular compartments. PMID- 20300735 TI - Altered parahippocampal functioning in cannabis users is related to the frequency of use. AB - RATIONALE: Converging lines of evidence suggest an association between cannabis use and impaired episodic memory as well as related associative learning. These deficits have been associated with the duration, frequency, and age of onset of cannabis use. However, it remains unclear whether these parameters of use differently impact memory-related hippocampal functioning. METHODS: Forty-two cannabis users were examined by means of functional magnetic resonance imaging while they encoded and retrieved face-profession associations. Region of interest analysis was subsequently used to compare (para-)hippocampal functioning in users with (1) a longer and shorter duration of use, (2) a higher and lower frequency of use, and (3) an earlier and later onset. To further separate the effects of these parameters of use on performance and (para-)hippocampal activity, linear regression analysis was applied. RESULTS: Compared to low-frequency users, high frequency users displayed stronger blood oxygenation level-dependent response during encoding in the left parahippocampal gyrus. No differences were obvious for the groups separated according to duration of use or an earlier and later onset of use. Linear regression analysis confirmed the association between a higher frequency of use and increased activity in the left parahippocampal gyrus. CONCLUSIONS: Our findings suggest that the frequency of use might have a particular critical impact on intact parahippocampal functioning in cannabis users. Increased activity within the encoding-related network might reflect functional compensation to maintain cognitive functioning. PMID- 20300736 TI - Comparison of the mass transfer in totally porous and superficially porous stationary phases in liquid chromatography. AB - The characterization of mass-transfer processes in a chromatographic column during a separation process is essential, since the influence of the mass transfer kinetics on the shape of the chromatographic band profiles and on the efficiency of the separation is crucial. Several sources of mass transfer in a chromatographic bed have been identified and studied: the axial dispersion in the stream of mobile phase, the external mass-transfer resistance, intraparticle diffusion, and the kinetics of adsorption-desorption. We measured and compared the characteristics and performance of a new brand of shell particles and those of a conventional brand of totally porous silica particles. The shell stationary phase was made of 2.7-microm superficially porous particles (a 1.7-microm solid core is covered with a 0.5-microm-thick shell of porous silica). The other material consisted of totally porous particles of conventional 3.5-microm commercial silica. We measured the first and second central moments of the peaks of human insulin over a wide range of mobile phase velocities (from 0.02 to 1.3 mL/min) at 20 degrees C. The plate height equations were constructed and the axial dispersion, external mass transfer, as well as the intraparticle diffusion coefficients were calculated for the two stationary phases. PMID- 20300738 TI - Solution to the beryllium valence challenge. PMID- 20300739 TI - Quantification of nitrotyrosine in nitrated proteins. AB - For kinetic studies of protein nitration reactions, we have developed a method for the quantification of nitrotyrosine residues in protein molecules by liquid chromatography coupled to a diode array detector of ultraviolet-visible absorption. Nitrated bovine serum albumin (BSA) and nitrated ovalbumin (OVA) were synthesized and used as standards for the determination of the protein nitration degree (ND), which is defined as the average number of nitrotyrosine residues divided by the total number of tyrosine residues in a protein molecule. The obtained calibration curves of the ratio of chromatographic peak areas of absorbance at 357 and at 280 nm vs. nitration degree are nearly the same for BSA and OVA (relative deviations <5%). They are near-linear at low ND (< 0.1) and can be described by a second-order polynomial fit up to ND=0.5 (R2>0.99). A change of chromatographic column led to changes in absolute peak areas but not in the peak area ratios and related calibration functions, which confirms the robustness of the analytical method. First results of laboratory experiments confirm that the method is applicable for the investigation of the reaction kinetics of protein nitration. The main advantage over alternative methods is that nitration degrees can be efficiently determined without hydrolysis or digestion of the investigated protein molecules. PMID- 20300740 TI - Validated HPAEC-PAD method for prebiotics determination in synbiotic fermented milks during shelf life. AB - Interest concerning functional food has been growing in recent years, and much attention has been focused on the choice of prebiotic fibers and probiotic microorganisms added to food products with the aim of improving health, producing synbiotic products. In the work reported here, an innovative analytical method performed by high-performance anion-exchange chromatography (HPAEC) with pulsed electrochemical detection has been optimized and validated for application to the study of prebiotic effects in synbiotic fermented milk prepared by addition of probiotics. The proposed method permits the evaluation of fructooligosaccharides and inulooligosaccharides with degrees of polymerization of 6-7 and 4-7, respectively. Quantitative determination was performed on oligosaccharides, whose standards are not commercially available, by employing calibration curves built by adding a known amount of the fiber used as an ingredient to the matrix. The work provides results from a parallel study on simultaneous variations of prebiotics and probiotics during the shelf life of fermented milk samples. The main advantage over time-consuming, classic enzymatic methods, whose results are limited only to average fiber content, is the possibility of dosing each carbohydrate by performing a single HPAEC run. Validation in terms of detection and quantitation limits, linearity, precision, and recovery was carried out. PMID- 20300741 TI - Paracetamol for intravenous use in medium--and intensive care patients: pharmacokinetics and tolerance. AB - PURPOSE: We studied the pharmacokinetics of paracetamol and determine the incidence of hypotension after intravenous administration in medium- (MCU) and intensive care (ICU) patients. METHODS: All patients on the ICU/MCU starting with paracetamol i.v. were included, yielding 38 patients. Blood samples were collected at predetermined time points to determine paracetamol serum concentration. The number of patients with a clinically relevant reduction in systolic blood pressure (SBP) and the number of patients that needed intervention to regain an acceptable blood pressure level were assessed. RESULTS: Overall, pharmacokinetic data were roughly comparable with earlier publications, but differences were noted in the subgroup ICU patients. Also, there was a trend to a larger peak serum concentration (p = 0.052) and a significantly smaller volume of distribution (p = 0.033) in MCU patients compared with ICU patients. Twenty-two percent (22%) and 33% of patients had a clinically relevant reduction in systolic blood pressure (SBP) 15 and 30 min after start of paracetamol infusion, respectively. In six patients (16%), an intervention was needed to correct blood pressure. Overall, SBP was significantly reduced at T = 15 min and 30 min postinfusion (p < 0.003 at both time points) when compared with SBP at the start of paracetamol infusion. CONCLUSIONS: Further research on differences in paracetamol pharmacokinetics between ICU and MCU patients is warranted, as these differences might result in differences in efficacy. Furthermore, administration of paracetamol i.v. as potential cause of hypotension in the critically ill patient must not be overlooked. PMID- 20300742 TI - Norwegian medical students' attitudes towards the pharmaceutical industry. AB - OBJECTIVE: Whereas there is a considerable body of information on the interaction between physicians and the pharmaceutical industry, little is known about the pharmaceutical industry-medical student relationship. We have assessed the extent of contact between Norwegian medical students and the pharmaceutical industry as well as the attitudes of these students towards the pharmaceutical industry. METHODS: A self-assessment questionnaire was distributed to fifth- and sixth-year students attending the four medical schools in Norway and to Norwegian medical students attending selected universities abroad. RESULTS: A total of 65.8% of all eligible students returned a completed questionnaire. Of these, 73.9% had been exposed to various levels of contact with the pharmaceutical industry, but only 17.5% reported having a generally positive attitude towards the industry. The level of exposure did not correlate in students' attitudes; rather, it correlated positively to a feeling of competence in terms of being able to handle such interactions. A majority of students responded that while they would decline accepting monetary gifts, they would welcome receiving reimbursements for meeting expenses, meals and educational material. Students favoured a practice of full disclosure of potential industry-related conflicts of interest among the university teaching staff. There were considerable differences in the students' attitudes between universities, suggesting that medical students are prone to influence from university lecturers. CONCLUSIONS: Norwegian medical students are opinionated, critical and curious with respect to pharmaceutical industry relations. This interest can be explored and probably also modified by educational initiatives. PMID- 20300743 TI - Comparison of plasma, venous and capillary blood levels of piperaquine in patients with uncomplicated falciparum malaria. AB - PURPOSE: Dihydroartemisinin-piperaquine (DP) is a fixed-dose artemisinin-based combination treatment. Field pharmacokinetic studies would be simplified and facilitated by being able to use small volume capillary assays rather than venous blood. The aim of this study was to describe the relationship between piperaquine concentrations measured in capillary blood, venous blood and venous plasma. METHODS: Samples of plasma, whole blood obtained by venesection and capillary blood were taken simultaneously from patients with uncomplicated Plasmodium falciparum malaria treated with DP between 0 and 9 weeks after treatment. Piperaquine concentrations in venous and capillary samples were measured using solid phase extraction and analysis by liquid chromatography with ultraviolet detection. RESULTS: A total of 161 sets of the three measures were obtained from 54 patients. Piperaquine concentrations in the venous blood samples were approximately twofold higher and those in the capillary blood samples were threefold higher than the corresponding venous plasma concentrations. Capillary blood piperaquine concentrations were approximately 1.7-fold higher than venous blood concentrations, and this difference also increased with time. CONCLUSION: Differences in whole blood and plasma levels of piperaquine suggest compartmentalisation of the drug within blood cells, as also occurs with the structurally related quinoline chloroquine. The relationship between piperaquine concentrations in the venous plasma, venous blood and capillary blood is variable and unpredictable at low concentrations. However, within the range of concentrations usually present in patients between 3 and 21 days after treatment with currently recommended doses, the relationship between capillary and venous whole blood is predictable; consequently, capillary blood sampling can be used in field assessments. PMID- 20300745 TI - Toxicity of the insecticide etofenprox to three life stages of the grass shrimp, Palaemonetes pugio. AB - Opportunities for environmental contamination by the insecticide etofenprox are increasing as its uses expand from primarily indoor residential to rice cultivation and mosquito control. To provide toxicity data for sensitive saltwater species, effects of etofenprox were assessed using three life stages of the estuarine grass shrimp, Palaemonetes pugio. Adults, larvae, and embryos were tested in aqueous exposures, while adults and larval shrimp were also tested in the presence of sediment. In addition, sublethal cellular stress biomarkers, glutathione and lipid peroxidation, were examined. Larval shrimp was the most sensitive life stage, with 96-h median lethal concentration (LC(50)) of 0.89 microg/l, compared with 1.26 microg/l for adults and 100 microg/l for embryos. Presence of sediment significantly decreased toxicity of etofenprox to both adult and larval shrimp. Etofenprox exposure (100 micog/l) increased time to hatch in embryos. Lipid peroxidation levels were reduced in adult and larval shrimp after 96 h exposure to etofenprox, while no effect on glutathione was detected. The results of this study provide new information on the toxicity of etofenprox to estuarine invertebrates. These data may prove beneficial to the regulation of this pesticide and management of its uses in coastal areas. PMID- 20300744 TI - Nonenzymatic augmentation of lactate transport via monocarboxylate transporter isoform 4 by carbonic anhydrase II. AB - Monocarboxylate transporters (MCTs) are carriers of high-energy metabolites like lactate and pyruvate, and different MCT isoforms are expressed in a wide range of cells and tissues. Transport activity of MCT isoform 1 (MCT1), heterologously expressed in Xenopus oocytes, has previously been shown to be supported by carbonic anhydrase II (CAII) in a noncatalytic manner. In the present study, we investigated possible interactions of CAII with MCT4, expressed in Xenopus oocytes. MCT4 transport activity is enhanced both by injected and by coexpressed CAII, similar to MCT1, with the highest augmentation at low extracellular pH and low lactate concentrations. CAII-induced augmentation in MCT4 transport activity is independent from the enzyme's catalytic function, as shown by application of the CA inhibitor ethoxyzolamide and by coexpression of MCT4 with the catalytically inactive mutant CAII-V143Y. PMID- 20300746 TI - Therapeutic strategies in children with an isolated unilaterally absent proximal pulmonary artery. AB - Therapeutic strategies for isolated unilateral absence of a proximal pulmonary artery remain unclear. The natural history of the disease, or thrombosis of primary surgical anastomosis, leads to exclusion of the affected lung with increased risk of intrapulmonary bleeding, impaired quality of life, and shortened life expectancy. We herein describe our two-stage approach in a small series of patients starting with interventional catheterization followed by surgical anastomosis. Other medical interventions, such as anticoagulation and pulmonary vasodilatation, are key factors to successfully restore pulmonary circulation in this rare defect. PMID- 20300747 TI - A new coupon design for simultaneous analysis of in situ microbial biofilm formation and community structure in drinking water distribution systems. AB - This study presents a new coupon sampling device that can be inserted directly into the pipes within water distribution systems (WDS), maintaining representative near wall pipe flow conditions and enabling simultaneous microscopy and DNA-based analysis of biofilms formed in situ. To evaluate this sampling device, fluorescent in situ hybridization (FISH) and denaturing gradient gel electrophoresis (DGGE) analyses were used to investigate changes in biofilms on replicate coupons within a non-sterile pilot-scale WDS. FISH analysis demonstrated increases in bacterial biofilm coverage of the coupon surface over time, while the DGGE analysis showed the development of increasingly complex biofilm communities, with time-specific clustering of these communities. This coupon design offers improvements over existing biofilm sampling devices in that it enables simultaneous quantitative and qualitative compositional characterization of biofilm assemblages formed within a WDS, while importantly maintaining fully representative near wall pipe flow conditions. Hence, it provides a practical approach that can be used to capture the interactions between biofilm formation and changing abiotic conditions, boundary shear stress, and turbulent driven exchange within WDS. PMID- 20300748 TI - A novel nitric oxide producing probiotic patch and its antimicrobial efficacy: preparation and in vitro analysis. AB - Microbial and fungal infections are a significant consideration in the etiology of all wounds. Numerous antimicrobial and antifungal formulations have been developed with varying degrees of efficacy and stability. Here, we report a nitric oxide producing probiotic adhesive patch device and investigate its antimicrobial and antifungal efficacy in vitro. This probiotic patch utilizes the metabolic activity of immobilized lactic acid bacteria, glucose, and nitrite salts for the production of gaseous nitric oxide (gNO), which is used as an antimicrobial agent against bacterial and fungal pathogens. Results show that application of gNO-producing probiotic patches to cultures of E. coli, S. aureus, P. aeruginosa, MRSA, T. mentagrophytes, and T. rubrum resulted in complete cell death at between 4 and 8 h, and application to cultures of A. baumannii, resulted in fewer than ten colonies detected per milliliter at 6 h. These results demonstrate that a gNO-producing probiotic patch device containing bacteria, glucose, and nitrite salts can produce sufficient levels of gNO over a therapeutically relevant duration to kill common bacterial and fungal wound pathogens in humans. PMID- 20300749 TI - Impact of peritoneal dialysis versus hemodialysis on incidence of intra-abdominal infection after simultaneous pancreas-kidney transplant. AB - BACKGROUND: Whether peritoneal dialysis is a risk factor for the development of intra-abdominal infection after simultaneous pancreas-kidney (SPK) transplantation is controversial. METHODS: We investigated the incidence of intra abdominal infection and graft survival rates in 100 patients who underwent SPK transplantation. Prior to transplantation, 25 patients received peritoneal dialysis (PD) and 75 received hemodialysis (HD); mean duration of dialysis was 25 +/- 35 months and 17 +/- 10 months, respectively. RESULTS: The two groups displayed similar gender distribution, cold ischemia time, dialysis duration, diabetes duration, and method of exocrine drainage. Intra-abdominal infections developed in 23 patients in the HD group (30%) and in 6 (24%) patients in the PD group (P = 0.41). In the HD group, 61% of patients with intra-abdominal infections had grades 3 and 4 complications requiring surgery, compared with only 33% in the PD group. The 1-year pancreas graft survival rate was 88% for HD and 94% for PD (P = 0.67) (mean follow-up = 55 +/- 38 months). There were no significant intergroup differences in acute rejection episodes, kidney graft survival rates, or length of hospital stay. CONCLUSIONS: In our experience, PD prior to SPK transplantation is not associated with increased incidence of intra abdominal infection compared to HD. PMID- 20300750 TI - Pelvic arterial embolisation in a trauma patient with a pre-existing aortobifemoral graft. AB - Pelvic fractures secondary to blunt trauma are associated with a significant mortality rate due to uncontrolled bleeding. Interventional radiology (IR) can play an important and central role in the management of such patients, offering definitive minimally invasive therapy and avoiding the need for high-risk surgery. Rapid access to whole-body computed tomography has been shown to improve survival in polytrauma patients and allows rapid diagnosis of vascular injury and assessment of suitability for endovascular therapy. IR can then target and treat the specific area of bleeding. Embolisation of bleeding pelvic arteries has been shown to be highly effective and should be the treatment of choice in this situation. The branches of the internal iliac artery (IIA) are usually involved, and these arteries are accessed by way of IIA catheterisation after abdominal aortography. Occasionally these arteries cannot be accessed by way of this conventional route because of recent IIA ligation carried out surgically in an attempt to stop the bleeding or because (in the rare situation we describe here) these vessels are excluded secondary to previous aortoiliac repair. In this situation, knowledge of pelvic arterial collateral artery pathways is important because these will continue to supply pelvic structures whilst making access to deep pelvic branches challenging. We describe a rare case, which has not been previously reported in the literature, in which successful embolisation of a bleeding pelvic artery was carried out by way of the collateral artery pathways. PMID- 20300751 TI - Arterial distribution of calibrated tris-acryl gelatin and polyvinyl alcohol embolization microspheres in sheep uterus. AB - The purpose of this study was to compare, after embolization, the distribution in the uterine arterial vasculature of tris-acryl gelatin microspheres (TGMS) and polyvinyl alcohol microspheres (PVAMS). A limited bilateral uterine artery embolization was performed in six adult sheep under fluoroscopic control by injecting in each uterine artery 0.25 ml of 500- to 700-microm TGMS of PVAMS suspended in 50/50 saline/contrast medium. Sacrifices were performed 1 week after embolization and uteri were analyzed histologically. The number and size of microspheres and vessels were measured, as well as the histological location according to a classification in four zones of the uterus. One hundred sixty-five vessels (69 vessels occluded with TGMS and 96 vessels occluded with PVAMS) were measured. The size of the occluded vessels decreased significantly from proximal to distal zones of the uterine vasculature (P < 0.0001). The location of TGMS and PVAMS within the vasculature was significantly different (P < 0.0001) since PVAMS blocked significantly more distally than TGMS. Deformation of the microspheres within the tissue was greater for PVAMS (18.0% +/- 12.3%) than for TGMS (8.7% +/- 9.2%) (P < 0.0001). In conclusion, PVAMS have a more distal distribution in the sheep uterine vasculature, compared to TGMS. Such differences in partition, already described in the kidney embolization model, can ultimately explain the different clinical outcome reported with these two types of microspheres in uterine fibroid embolization. PMID- 20300752 TI - Screening and evaluating the mimic peptides as a useful serum biomarker of ankylosing spondylitis using a phage display technique. AB - To screen specific serum biomarker for ankylosing spondylitis (AS) using a phage random peptide library. A phage random peptide library of random peptide 12-mers was immunoscreened with purified immunoglobulin (Ig) G from sera of AS patients. Positive clones obtained after three rounds of biopanning were detected with ELISA and sequenced. Reaction of the screened positive clones with sera from AS patients, systemic lupus erythematosus (SLE) patients, rheumatoid arthritis (RA) patients, osteoarthritis (OA) patients and healthy controls was detected using phage ELISA. Correlation among erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and the absorbance value of the positive clone in phage ELISA was examined in AS patients. Seventeen out of twenty randomly selected phage clones exhibited specific reaction with purified sera IgG from AS patients, among them seven coming from the same clone whose inserted peptide sequence was LALPPLAPNHHH (named "AS1"). Phage ELISA results showed that the positive reaction rate of the AS1 clone was 92.0% with AS patients, significantly different (P < 0.01) from those with SLE patients (56.7%), RA patients (50.0%), OA patients (13.3%), and healthy controls (14.0%). Absorbance value of the AS1 clone in phage ELISA was significantly higher than those in the other groups (P < 0.05). In addition, the absorbance value of the AS1 clone showed no statistically significant correlation with ESR and CRP in AS patients, suggesting that AS1 detects AS patients through a unique mechanism other than inflammation. The short peptide AS1 obtained through screening of a phage random peptide library with purified serum IgG from AS patients can specifically react with the sera of AS patients, and thereby may be a candidate of AS-specific serum biomarkers. PMID- 20300753 TI - Polymyalgia rheumatica and vertebral fractures: a 1-year pilot controlled study. AB - No data exist about the possibility that vertebral fracture in PMR patients could be independent of steroid therapy. For this reason, we aimed to investigate this topic by a case cohort study with a 1-year follow-up for each patient. We selected ten consecutive patients who experienced vertebral fractures (VF-group) during the first month of 1-year follow-up period and without any other significant associated condition. As a control group we studied ten control patients, without vertebral fractures and with a follow-up of 1 year, randomly selected among a larger group of patients affected by polymyalgia rheumatica. The following data were analysed: eritrosedimention rate (ESR), visual analogical scale score (VAS), methyprednisolone daily dosage. Each patient had been monthly evaluated by the aforementioned clinical and laboratoristic parameters during the 1-year follow-up period. The VF-group resulted with a higher and statistically significant median corticosteroid 12-month total dosage [mean 3,480 mg (95%CI 2,805-3,030) vs. 2,760 mg (2,666.25-3,247.5)]. The VF-group had statistically significant higher ESR and VAS AUC when compared to control group (median ESR AUC, 484.75 vs. 288.25; P = 0.0001; median VAS AUC, 70.75 vs. 43.5 P < 0.0001); ESR at the baseline (cut-off >80 mm) showed a specificity of 90% (95%CI 56-100) and sensitivity of 70% (95%CI 35-93). VAS difference from first to second month (cut-off 20 IU/ml was defined as positive. 25-OH Vitamin D EIA Kit was used to measure serum 25-OH Vitamin D levels. We found that the mean of the 25-OH D vitamin levels of the patients with RA was not different than that of controls (P = 0.936). We divided patients with RA into three groups according to DAS28 as low activity group (group 1, n = 25), moderate activity group (group 2, n = 25), and high activity group (group 3, n = 15). 25-OH vitamin D levels of the patients in the high activity group (group 3) were found to be the lowest (P < 0.001), and the patients with moderate disease activity had lower levels than those in the mild group (P = 0.033). Serum 25-OH vitamin D levels were significantly negatively correlated with DAS28, CRP, and HAQ (respectively, r = -0.431, P = 0.000, r = -0.276, P = 0.026, and r = -0.267, P = 0.031). Serum vitamin D levels in patients with RA were similar those in the healthy controls, while it significantly decreases in accordance with the disease activity and decreasing functional capacity. PMID- 20300756 TI - Lack of association of FcgammaRIIIb polymorphisms with systemic lupus erythematosus: a meta-analysis. AB - Systemic lupus erythematosus (SLE) is a complex autoimmune disease. Fcgamma receptor genes have been suggested to play an important role in the pathogenesis of SLE and lupus nephritis (LN). This study aims to assess the association between FcgammaRIIIb-NA1/NA2 polymorphism and the susceptibility to SLE and lupus nephritis. Relevant studies were identified from electronic databases. A meta analysis was performed for heterogeneity test and pooled OR calculation. The overall OR of NA2/NA2 homozygous genotype and NA2 allele frequency showed no significant association with SLE and lupus nephritis. Similarly, the association between FcgammaRIIIb-NA1/NA2 polymorphism and SLE and lupus nephritis was not found in European and Asian population. Taken together, our results suggest that FcgammaRIIIb might not be a susceptibility gene for SLE and lupus nephritis. PMID- 20300758 TI - Ventriculosubgaleal shunt procedure and its long-term outcomes in premature infants with post-hemorrhagic hydrocephalus. AB - OBJECTIVE: It is well known that 10-15% of hydrocephalus cases at childhood and 40-50% in premature infants, occur following Germinal matrix hemorrhage (GMH). Such hemorrhages are reported to arise due to the rupture of germinal matrix (GM) vessels as a result of cerebral blood flow changes among infants with <1500 g birth weight and <32 weeks old. Intraventricular hemorrhage (IVH) associated with GMH leads to a disruption in the cerebrospinal fluid (CSF) and ventricular dilatation. Ventriculosubgaleal shunt (VSGS) is preferred in those hydrocephalus cases because it is a simple and rapid method, precludes the need for repetitive aspiration for evacuation of CSF, establishes a permanent decompression without causing electrolyte and nutritional losses, and aims to protect the cerebral development of newborns with GMH. MATERIAL AND METHOD: The present study comprises 25 premature cases, subjected to VSGS and diagnosed with post hemorrhagic hydrocephalus (PHH) arising from IVH associated with GM, and low birth weight (LBW) in the Neurosurgery Department of the Medical Faculty of Erciyes University between July 2002 and September 2006. VSGS surgery was performed on those cases, and their clinical and radiological prognoses were monitored with regard to several parameters. RESULTS: Mortality and morbidity results were found to be lower than those in PPH treatment methods. While prognosis of grade 4 GMHs was poor, grades 2 and 3 GMHs displayed a much better prognosis after VSGS along with complete recovery in some hydrocephalus cases. PMID- 20300759 TI - [Internal medicine and its core topics]. PMID- 20300761 TI - Causes and consequences of 93 fetuses with cardiomegaly in a tertiary center in Thailand. AB - OBJECTIVES: To assess etiology, perinatal mortality and associated factors of fetal cardiomegaly (FC). METHODS: A retrospective study of fetuses with cardiomegaly was conducted. Demographic data, ultrasonographic findings, and outcomes were collected and analyzed. RESULTS: Ninety-three fetuses were analyzed. The causes of FC were cardiac causes 49.5%, Bart's hemoglobinopathies 28%, and non-Bart's anemia 15%. Ascites, pericardial effusion, and hydrops were more prevalent in fetuses with anemia than those with cardiac abnormalities. The overall perinatal mortality was 69.9%. Although all Bart's hydrops died, perinatal mortality of non-Bart's anemia, and structural cardiac defect were 57.1 and 69.7%, respectively. Excluding Bart's anemia, receiver-operating characteristic curve analysis demonstrated that cardiothoracic ratio of >=0.58 best predictive for perinatal mortality. Earlier gestational age at diagnosis, skin edema, and chromosomal abnormality were associated with higher mortality. CONCLUSIONS: Majority causes of FC were cardiac and anemic in origin. It carried high-perinatal mortality depending on the causes. PMID- 20300760 TI - [Osteoarthritis in hereditary metabolic diseases]. AB - Primary osteoarthritis (OA) of peripheral joints is a common disease mainly occurring after the age of 50. It is important to distinguish primary from secondary OA. Younger age at disease onset, rapid progression, unusual disease manifestations and co-morbidities are signs of secondary OA. This review outlines an important group of secondary OA. Hereditary metabolic diseases can exhibit joint involvement. For some of these diseases, correct diagnosis is critical, since appropriate therapy influences not only joint function and quality of life, but can also prevent relevant end-organ damage. PMID- 20300762 TI - Pelvic angiomatosis: an unusual cause of recurrent obstructed labor: a case report and review of literature. AB - BACKGROUND: Pelvic angiomatosis is a very rare cause of obstructive labor. MATERIALS AND METHODS: A 26-year-old P2 L2 had two cesarean sections for recurrent obstructed labor due to a large pelvic mass. Investigations after the first cesarean section suggested a benign nature of the mass for which she was advised surgical resection, but she refused due to social reasons. Tumor had pelvic and extrapelvic part extending through obturator foramen into the right thigh. Resection of the pelvic part by abdominoperineal approach led to a profusely bleeding bed which was managed by ligation of bilateral internal iliac artery. Resection of extrapelvic part was attempted but it was abandoned due to hemodynamic instability of the patient. RESULTS: Patient is asymptomatic and is having a relatively static residual extrapelvic part of pelvic tumor for last 2 years. CONCLUSION: Pelvic angiomatosis is a very rare condition but should be considered and ruled out in case of a pelvic mass of uncertain origin. MRI plays an important role in the initial diagnosis, in surgical planning and in the follow-up in order to detect recurrences. Surgical resection should be as conservative as possible, balancing the need for complete surgical extirpation with the morbidity of the procedure. PMID- 20300763 TI - Olfactory bulb volume and depth of olfactory sulcus in patients with idiopathic olfactory loss. AB - Olfactory loss is considered as idiopathic (IOL) when no cause can be found, neither on the basis of a standardized history nor a thorough clinical evaluation. Olfactory bulb volume (OB) has been shown to be decreased in patients with olfactory loss due to trauma, infections, or sinonasal disease. However, OB volume has not yet been investigated in IOL patients. Twenty-two patients with IOL were compared with 22 controls in terms of olfactory performance and of OB volume assessed with magnetic resonance imaging (MRI). Psychophysical testing confirmed that patients had lower scores than controls: P < 0.001 for threshold (T), discrimination (D), identification (I) and global TDI score. Mean right, left and total OB volumes were significantly smaller for IOL patients as compared to controls. Both for IOL and controls, there was a significant correlation between odor thresholds and total OB volume, respectively. In conclusion, patients with IOL have decreased olfactory function and decreased OB volume when compared with controls. This was previously demonstrated for patients with postinfectious or posttraumatic olfactory dysfunction, but not for patients with uneventful conditions possibly damaging their olfactory apparatus. PMID- 20300764 TI - News on treatment: from antiepileptics in childhood absence epilepsy to improvement of falls in Parkinson's disease by deep brain stimulation. PMID- 20300765 TI - Fundus autofluorescence and spectral-domain optical coherence tomography findings of leopard spots in nanophthalmic uveal effusion syndrome. AB - PURPOSE: To describe fundus autofluorescence (FAF) imaging and spectral domain optical coherence tomography (SD-OCT) findings of leopard spots in nanophthalmic uveal effusion syndrome. METHODS: A 34-year-old man with retinal detachment associated with nanophthalmic uveal effusion syndrome in the right eye underwent sclerotomy three times. After the final surgery, the subretinal fluid resolved gradually. Then, SD-OCT examination, FAF photography, fluorescein angiography (FA), and indocyanine green angiography (ICGA) were performed simultaneously with the spectralis Heidelberg retina angiograph + OCT system. RESULTS: SD-OCT revealed focal thickening of the retinal pigment epithelium (RPE) layer at the same locations as leopard spots, which appeared hypofluorescent on FA and ICGA. These spots showed hyperautofluorescence on FAF imaging. Six months later, focal thickening of the RPE layer became smaller on OCT and hyperautofluorescence was attenuated on FAF imaging. CONCLUSIONS: Simultaneous imaging of the fundus with multiple modalities including OCT, FAF, FA, and ICGA indicates that leopard spots in the fundus of uveal effusion syndrome may show hyperautofluorescence and correspond to focal thickening of the RPE layer by SD-OCT. This imaging method may help elucidate the pathology of various fundus lesions in vivo. PMID- 20300766 TI - Early high-dose intravenous methylprednisolone is effective in preserving retinal nerve fiber layer thickness in patients with neuromyelitis optica. AB - BACKGROUND: Neuromyelitis optica (NMO) is a recurring inflammatory neurological disease characterized by severe optic neuritis and myelitis. The purpose of this study was to determine whether the retinal nerve fiber layer thickness (RNFLT) is correlated with the clinical presentations in patients with NMO and to determine the clinical factors that lead to poor visual outcomes. METHODS: Thirty-five eyes of 18 patients with the NMO spectrum and 28 eyes of 14 patients with multiple sclerosis (MS) were studied. All of the patients had at least one episode of optic neuritis (ON) >6 months before being studied. The eyes were classified into four groups based on an episode of ON: NMO-ON, NMO eyes with at least one episode of ON; NMO-nonON, NMO eyes without an episode of ON; MS-ON, MS eyes with at least one episode of ON; and MS-nonON, MS eyes without an episode of ON. The RNFLT was measured by optical coherence tomography (OCT). The correlations between the RNFLT and the clinical data were determined. RESULTS: The overall RNFL was thinner in patients in the NMO-ON group than in the MS-ON group (63.84 um vs. 84.28 um; p = 0.0006) especially in the superior and inferior quadrants. The overall RNFLT was significantly correlated with the best-corrected visual acuity (BCVA) in both the NMO groups (r = 0.67; p < 0.0001) and the MS groups (r = 0.62; p = 0.0097). The overall RNFLT was negatively correlated with the number of relapses in the NMO group. A receiver operating characteristic (ROC) analysis showed that the cut-off value for a decrease in visual acuity to <20/20 was 71.41 um of the overall RNFLT in the NMO group. The frequency of the ON relapses and the time for beginning the treatment with high-dose intravenous methylprednisolone (HIMP) significantly affected the preservation of the RNFLT. CONCLUSIONS: The overall thinner RNFL in eyes with NMO than in eyes with MS indicates a greater loss of optic nerve axons in eyes with NMO. An early intervention with HIMP and preventing recurrences in NMO are critical for minimizing the axonal loss. Our findings indicate that OCT is an important method of evaluating loss of optic nerve axons in eyes with NMO and MS. PMID- 20300768 TI - Cold-induced vasoconstriction at forearm and hand skin sites: the effect of age. AB - During mild cold exposure, elderly are at risk of hypothermia. In humans, glabrous skin at the hands is well adapted as a heat exchanger. Evidence exists that elderly show equal vasoconstriction due to local cooling at the ventral forearm, yet no age effects on vasoconstriction at hand skin have been studied. Here, we tested the hypotheses that at hand sites (a) elderly show equal vasoconstriction due to local cooling and (b) elderly show reduced response to noradrenergic stimuli. Skin perfusion and mean arterial pressure were measured in 16 young adults (Y: 18-28 years) and 16 elderly (E: 68-78 years). To study the effect of local vasoconstriction mechanisms local sympathetic nerve terminals were blocked by bretylium (BR). Baseline local skin temperature was clamped at 33 degrees C. Next, local temperature was reduced to 24 degrees C. After 15 min of local cooling, noradrenaline (NA) was administered to study the effect of neural vasoconstriction mechanisms. No significant age effect was observed in vasoconstriction due to local cooling at BR sites. After NA, vasoconstriction at the forearm showed a significant age effect; however, no significant age effect was found at the hand sites. [Change in CVC (% from baseline): Forearm Y: -76 +/- 3 vs. E: -60 +/- 5 (P < 0.01), dorsal hand Y: -74 +/- 4 vs. E: -72 +/- 4 (n.s.), ventral hand Y: -80 +/- 7 vs. E: -70 +/- 11 (n.s.)]. In conclusion, in contrast to results from the ventral forearm, elderly did not show a blunted response to local cooling and noradrenaline at hand skin sites. This indicates that at hand skin the noradrenergic mechanism of vasoconstriction is maintained with age. PMID- 20300767 TI - Ten-year follow-up of photorefractive keratectomy for myopia. AB - BACKGROUND: The aim of this study is to evaluate the long-term (10-year) outcome of excimer laser photorefractive keratectomy (PRK) on myopic eyes. METHODS: This retrospective study included 42 eyes of 29 patients (13 male, 16 female; mean age 33.4 years, range 21 to 60) who were treated with myopic PRK at St. Luke's International Hospital, Tokyo, Japan, from May 1 1995 to December 31 1998, and followed up for more than 10 years. The main outcome measures were efficacy, predictability, stability, safety, and complications. We also evaluated the progress of intraocular pressure, corneal thickness, and endothelial cell density after the surgery. The cases of retreatments were excluded from this study. RESULTS: Ten years after the surgery, 17 eyes (40%) had 20/20 vision or better, and 35 eyes (81%) had 20/40 or better. With regard to the refractive predictability, 55 percent of the eyes were within +/- 1.0D and 76% were within +/- 2.0D, 10 years after the surgery. There was myopic regression with a mean change in refraction of-0.51 +/- 1.78D. Best spectacle-corrected visual acuity (BCVA) was unchanged or improved in 95%, and only two eyes lost 1 line of BCVA. The mean corneal haze score was 0.19 +/- 0.40, and the decreasing rate of endothelial cell was 8.30 +/- 9.94% at 10 years, which was slightly higher than the spontaneous decreasing rate with age. CONCLUSIONS: PRK is safe and effective in refraction even 10 years after surgery; however, further long-term follow-up is needed to evaluate the decreasing of endothelial cells. PMID- 20300769 TI - Exercise training-induced enhancement in myocardial mechanics is lost after 2 weeks of detraining in rats. AB - Exercise training is assumed to improve myocardial function; however, the role of detraining and its effect on myocardial parameters are still unclear. The aim of the present study was to evaluate the effect of detraining on ventricular remodeling and myocardial mechanical parameters after an 8 week (5 days/week, 60 min/day) swimming training period. Forty-three female Wistar rats were distributed into six groups: trained (T, n = 9), detrained 2 weeks (D2, n = 8), detrained 4 weeks (D4, n = 8) and their respective controls: untrained (U, n = 5), untrained 2 weeks (U2, n = 5) and untrained 4 weeks (U4, n = 5). Detrained rats underwent training and then remained sedentary (i.e., "detraining") for 2 or 4 weeks. After training, the T group demonstrated increased physical capacity, left ventricular (LV) posterior wall thickness, and LV end-diastolic diameter, along with decreased heart rate, as evaluated by echocardiogram. In addition, the inotropism and lusitropism parameters studied on papillary muscles showed improvement in the T group (P < 0.05). However, after just 2 weeks of detraining, all parameters regressed back to values which were similar to those of the untrained groups. In conclusion, our results confirmed that exercise training is capable of inducing myocardial remodeling and improving contractile performance; however, these changes are completely lost after a short period of detraining. PMID- 20300770 TI - Successful evaluation of a new animal model using mice for esophageal adenocarcinoma. AB - INTRODUCTION: For the better understanding of the pathophysiological events occurring in the sequence inflammation-metaplasia-carcinoma in esophageal adenocarcinoma, an animal model would be desirable. In the past, several rat models have been used yielding conflicting results. Some demonstrated a sequence similar to the human situation whereas others failed to initiate true esophageal adenocarcinoma or even Barrett's metaplasia. For the study of the molecular events involved in the carcinogenesis of Barrett's carcinoma, a mouse model would be much more promising since most of the genetically altered animals are mice. However, as of now no such model exists, in the past predominately due to the high mortality involved with the surgical procedure to create a mixed duodenogastric reflux. METHODS: Forty BALB-C mice weighing between 22 and 25 g underwent an esophagojejunostomy. The animals were sacrificed at 3, 4, and 5 months. Pathological evaluation was performed with HE staining. RESULTS: Overall mortality was 17%. However, mortality within the first ten animals was 30%. Reasons were technical problems with the anastomosis, opening of the pleural cavity, or bleeding events. All animals had a severe esophagitis regardless of the time. Intestinal metaplasia could be found in 60% of the animals after 4 months and esophageal adenocarcinoma in 55% after 5 months. One animal showed multiple lung metastases. CONCLUSION: After a certain learning curve esophagojejunostomy is feasible in mice with an acceptable mortality rate and leads to esophageal adenocarcinoma. PMID- 20300771 TI - Identification and optimization of tyrosine hydroxylase activity in Mucuna pruriens DC. var. utilis. AB - Tyrosine hydroxylase, an iron containing tetrahydrobiopterin dependent monooxygenase (tyrosine 3-monooxygenase; EC 1.14.16.2), catalyzes the rate limiting step in which L: -dopa is formed from the substrate L-tyrosine. L-Dopa concentration and activity of L-tyrosine hydroxylase enzyme were measured in roots, stem, leaves, pods, and immature seeds of Mucuna pruriens. Immature seeds contained maximum L-dopa content and mature leaves possessed maximum catalytic activity of tyrosine hydroxylase. Tyrosine hydroxylase from leaf homogenate was characterized as a 55 kDa protein by SDS-PAGE and Western-blot analysis with monoclonal mouse IgG2a tyrosine hydroxylase antibody. The conditions for maximum tyrosine hydroxylase activity from the leaf extract were optimized with respect to temperature, pH, cofactor 6-MPH(4), and divalent metal ions. The tyrosine hydroxylase from leaf extract possessed a K (m) value of 808.63 microM for L tyrosine at 37 degrees C and pH 6.0. The activity of the enzyme was slightly inhibited at 2,000 microM L-tyrosine. Higher concentrations of the cofactor 6 MPH(4), however, completely inhibited the synthesis of L-dopa. Tyrosine hydroxylase converted specific monophenols such as L-tyrosine (808.63 microM) and tyramine (K (m) 1.1 mM) to diphenols L-dopa and dopamine, respectively. Fe(II) activated the enzyme while higher concentration of other divalent metals reduced its activity. For the first time, tyrosine hydroxylase from M. pruriens is being reported in this study. PMID- 20300772 TI - Sporadic hybrid oncocytic/chromophobe tumor of the kidney: a clinicopathologic, histomorphologic, immunohistochemical, ultrastructural, and molecular cytogenetic study of 14 cases. AB - Hybrid oncocytic/chromophobe tumors (HOCT) of the kidney have been described in patients with Birt-Hogg-Dube syndrome (BHD) and in association with renal oncocytosis without BHD. HOCT in patients without evidence of BHD or renal oncocytosis is exceedingly rare, and these cases have been poorly characterized. We have identified and studied 14 cases of HOCT from previously diagnosed renal oncocytomas (398 cases) and chromophobe renal cell carcinomas (351 cases) without evidence of BHD or renal oncocytosis. Immunohistochemical, ultrastructural, and molecular genetic studies analyzing numerical chromosomal changes, loss of heterozygosity for chromosome 3p, and mutation status of VHL, c-kit, PDGFR, and folliculin (FLCN) genes were performed. HOCTs were identified in nine men and five women (age range 40-79 years). The size of tumors ranged from 2 to 11 cm. All tumors displayed a solid alveolar architecture and were composed of cells with abundant granular eosinophilic oncocytic cytoplasm with perinuclear halos. Occasional binucleated neoplastic cells were present, but irregular, hyperchromatic, wrinkled (raisinoid) nuclei were absent. The cytoplasm contained numerous mitochondria of varying sizes, but only sparse microvesicles with amorphic lamellar content were found. Tumors were positive for CK7 (12/14), AE1 AE3 (14/14), anti-mitochondrial antigen (14/14), E-cadherin (11/13), parvalbumin (12/14), and epithelial membrane antigen (14/14). Tumors were generally negative for racemase, CK20, CD10, and carboanhydrase IX. Interphase fluorescence in situ hybridization revealed multiple chromosomal losses and gains with a median of four (range 1-9) chromosomal aberrations per case. Monosomy of chromosome 20 was common and found in 7 of 14 cases. Monosomy of chromosomes 6 and 9 was present in 4 of 14 cases each, of which two cases displayed monosomy for both chromosomes 6 and 9. Polysomy of chromosomes 10, 21, and 22 was found in 4/14 cases each, of which one case displayed polysomy for all these three chromosomes. No pathogenic mutations were found in the VHL, c-kit, PDGFR, and folliculin (FLCN) genes. (1) We have shown that hybrid oncocytic/chromophobe tumors of the kidney do occur, albeit rarely, outside the Birt-Hogg-Dube syndrome and without associated renal oncocytosis. (2) These tumors constitute a relatively homogenous group with histomorphologic features of both chromophobe renal cell carcinoma and renal oncocytoma. (3) Sporadic hybrid oncocytic/chromophobe renal tumors are characterized by multiple numerical aberrations (both mono- and polysomies) of chromosomes 1, 2, 6, 9, 10, 13, 17, 21, and 22 and lack of mutations in the VHL, c-kit, PDGFRA, and FLCN genes. (4) The tumors seem to behave indolently as no evidence of malignant behavior was documented in our series, although admittedly, the follow-up was too short to fully elucidate the biological nature of this rare neoplasm. At worst, these tumors could have a low malignant potential, which only can be found out with longer follow-up. PMID- 20300773 TI - Co-expression of CD173 (H2) and CD174 (Lewis Y) with CD44 suggests that fucosylated histo-blood group antigens are markers of breast cancer-initiating cells. AB - Histo-blood group antigens CD173 (H2) and CD174 (Lewis Y) are known to be developmentally regulated carbohydrate antigens which are expressed to a varying degree on many human carcinomas. We hypothesized that they might represent markers of cancer-initiating cells (or cancer stem cells, CSC). In order to test this hypothesis, we examined the co-expression of CD173 and CD174 with stem cell markers CD44 and CD133 by flow cytometry analysis, immunocytochemistry, and immunohistochemistry on cell lines and tissue sections from breast cancer. In three breast cancer cell lines, the percentage of CD173(+)/CD44(+) cells ranged from 17% to >60% and of CD174(+)/CD44(+) from 21% to 57%. In breast cancer tissue sections from 15 patients, up to 50% of tumor cells simultaneously expressed CD173, CD174, and CD44 antigens. Co-expression of CD173 and CD174 with CD133 was also observed, but to a lesser percentage. Co-immunoprecipitation and sandwich ELISA experiments on breast cancer cell lines suggested that CD173 and CD174 are carried on the CD44 molecule. The results show that in these tissues CD173 (H2) and CD174 (LeY) are associated with CD44 expression, suggesting that these carbohydrate antigens are markers of cancer-initiating cells or of early progenitors of breast carcinomas. PMID- 20300774 TI - Preschoolers' and parents' asthma education trial (P2AET)--a randomized controlled study. AB - We aimed to evaluate a family-oriented psycho-educational asthma training program for the age group of 2-5 years, involving both parents and children. Children were included after having at least 3 obstructive episodes in their life plus chronic or recurrent wheeze in the 6 months before the start of the study. In the multicenter randomized trial we had (1) a waiting group (WG), (2) an instruction group (IG) trained in a structured way according to the national asthma guideline, and (3) an education group (EG), having a standardized multiprofessional psycho-educational program, according to the national licensed asthma education for the age group of 6-18 years. All were assessed after 6 months. A subgroup analysis was performed on those being on regular inhaled corticosteroids at study entry (74.3%). A total of 338 children were randomized, and 288 (85%) completed the study. In the asthma emergency management, test scores increased most in EG, less in IG, and not in WG. For emergency visits the risk ratio for EG was 0.68 compared to IG: Patients regularly inhaling corticosteroids (74.3%) had an increased risk for emergency visits when having only an instruction (OR 3.99 [1.89-8.40]) or had been waiting (OR 2.5 [1.16 5.37]) when compared to those having an asthma education. We conclude that in the German health system, the family oriented psycho-educational program provided in a standardized manner by a multiprofessional team is effective also in the age group of 2-5 years. It should be made accessible to each asthmatic child. PMID- 20300775 TI - PTEN mutation spectrum in breast cancers and breast hyperplasia. AB - PURPOSE: Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) is one of the most frequently mutated human tumor suppressor genes. The present study aims to investigate the role of PTEN mutation in breast carcinogenesis by analyzing PTEN mutation spectrum and the protein expression in breast cancers, adjacent hyperplastic lesions, benign breast lesions and normal breast tissues. METHODS: All 9 exons of PTEN gene were amplified by PCR with DNA extracted from 50 of human breast cancers and corresponding adjacent breast hyperplasia tissues, adjacent normal breast tissues, as well as 50 breast benign lesions residing in or around Yunnan, China, respectively. PCR products were then sequenced for mutation screening. And we also proved the effect of mutations on the expression of PTEN protein by immunohistochemistry. RESULTS: PTEN mutations were detected in 11 of 50 (22%) breast cancers and 4 of 50 (8%) adjacent ductal hyperplasia, all of which were atypical ductal hyperplasia and same PTEN mutation were detected in the corresponding cancer tissues. No PTEN mutation was detected in all adjacent normal breast tissues and 50 cases of breast benign lesions. The mutation sites concentrated at exon 3, 4, 5 and 7; no mutation was detected in exon 1, 2, 6, 8, or 9 and splicing sites of all introns. The hottest mutation spots were exon 5 with missense mutations. Immunohistochemical analysis showed that 24 of 50 (48%) breast cancers and 6 of 50 (12%) adjacent breast hyperplasia demonstrated negative immuno-staining of PTEN (loss of PTEN protein expression). All the 4 adjacent breast tissues harbored PTEN mutations and 9 of 11 breast cancers with PTEN mutation were loss of PTEN expression. Statistical analysis revealed that PTEN gene mutations were correlated with the PTEN expression. CONCLUSIONS: The incidence of PTEN mutations is relatively high in patients with sporadic breast cancer in the region of Yunnan, China and exists at the early stage of breast cancer development. The PTEN mutations have significant effect on the expression silencing of PTEN protein indicating the important role of PTEN mutation in carcinogenesis of breast cancers. PMID- 20300776 TI - Plasticity in response to phosphorus and light availability in four forest herbs. AB - The differential ability of forest herbs to colonize secondary forests on former agricultural land is generally attributed to different rates of dispersal. After propagule arrival, however, establishing individuals still have to cope with abiotic soil legacies from former agricultural land use. We focused on the plastic responses of forest herbs to increased phosphorus availability, as phosphorus is commonly found to be persistently bioavailable in post-agricultural forest soils. In a pot experiment performed under field conditions, we applied three P levels to four forest herbs with contrasting colonization capacities: Anemone nemorosa, Primula elatior, Circaea lutetiana and Geum urbanum. To test interactions with light availability, half of the replicas were covered with shade cloths. After two growing seasons, we measured aboveground P uptake as well as vegetative and regenerative performance. We hypothesized that fast-colonizing species respond the most opportunistically to increased P availability, and that a low light availability can mask the effects of P on performance. All species showed a significant increase in P uptake in the aboveground biomass. The addition of P had a positive effect on the vegetative performances of two of the species, although this was unrelated to their colonization capacities. The regenerative performance was affected by light availability (not by P addition) and was related to the species' phenology. Forest herbs can obviously benefit from the increased availability of P in post-agricultural forests, but not all species respond in the same way. Such differential patterns of plasticity may be important in community dynamics, as they affect the interactions among species. PMID- 20300777 TI - Simulating phenological shifts in French temperate forests under two climatic change scenarios and four driving global circulation models. AB - After modeling the large-scale climate response patterns of leaf unfolding, leaf coloring and growing season length of evergreen and deciduous French temperate trees, we predicted the effects of eight future climate scenarios on phenological events. We used the ground observations from 103 temperate forests (10 species and 3,708 trees) from the French Renecofor Network and for the period 1997-2006. We applied RandomForest algorithms to predict phenological events from climatic and ecological variables. With the resulting models, we drew maps of phenological events throughout France under present climate and under two climatic change scenarios (A2, B2) and four global circulation models (HadCM3, CGCM2, CSIRO2 and PCM). We compared current observations and predicted values for the periods 2041 2070 and 2071-2100. On average, spring development of oaks precedes that of beech, which precedes that of conifers. Annual cycles in budburst and leaf coloring are highly correlated with January, March-April and October-November weather conditions through temperature, global solar radiation or potential evapotranspiration depending on species. At the end of the twenty-first century, each model predicts earlier budburst (mean: 7 days) and later leaf coloring (mean: 13 days) leading to an average increase in the growing season of about 20 days (for oaks and beech stands). The A2-HadCM3 hypothesis leads to an increase of up to 30 days in many areas. As a consequence of higher predicted warming during autumn than during winter or spring, shifts in leaf coloring dates appear greater than trends in leaf unfolding. At a regional scale, highly differing climatic response patterns were observed. PMID- 20300778 TI - Effect of intraoperative acetated Ringer's solution with 1% glucose on glucose and protein metabolism. AB - PURPOSE: To investigate the effects of the intraoperative administration of Ringer's solution with 1% glucose on the metabolism of glucose, lipid and muscle protein during surgery. METHODS: Thirty-one adult patients, American Society of Anesthesiologists physical status I or II, undergoing elective otorhinolaryngeal, head and neck surgeries were randomly assigned to one of two patient groups: those receiving acetated Ringer's solution with 1% glucose (Group G) or those receiving acetated Ringer's solution without glucose (Group R) throughout the surgical procedure. Plasma glucose was measured at anesthetic induction (T0), artery 1 h (T1), 2 h (T2), 3 h after anesthetic induction (T3) and at the end of surgery (T4). Plasma ketone bodies, insulin and 3-methylhistidine were measured at T0 and T4. RESULTS: The intravenous infusion for patients in Group G and R was 6.1 + or - 0.8 and 6.3 + or - 1.7 ml/kg/h, respectively, with Group G patients receiving a dose of 4.1 g/h glucose. Plasma glucose levels were significantly higher in Group G than in Group R patients at T1, T2, T3 and T4; however, plasma glucose remained <150 mg/dl in both groups. The plasma concentration of ketone bodies was significantly higher (P < 0.05) in Group R than in Group G patients at T4. Changes in plasma 3-methylhistidine concentration was significantly lower in Group G than in Group R patients. These results indicate that acetated Ringer's solution with 1% glucose decreased protein catabolism without hyperglycemia among the Group G patients. CONCLUSION: The infusion of a small dose of glucose (1%) during minor otorhinolaryngeal, head and neck surgeries may suppress protein catabolism without hyperglycemia and hypoglycemia. PMID- 20300780 TI - Cardiac arrest in the left lateral decubitus position and extracorporeal cardiopulmonary resuscitation during neurosurgery: a case report. AB - Cardiopulmonary resuscitation (CPR) in the lateral position during noncardiac surgery has been described in only a few reports in the past. Here, we report a case of cardiac arrest in a 61-year-old man undergoing microvascular decompression surgery for trigeminal neuralgia in the left lateral decubitus position. During the initial 5 min of CPR, chest compression was performed in this position by two rescuers; one from the chest and the other from the back, pushing simultaneously. Because ventricular arrhythmia was refractory to conventional CPR even after placing the patient back to the supine position, extracorporeal life support was introduced in the operating room by using the femoro-femoral approach (right atrio-femoral veno-arterial bypass). This alternative CPR markedly decreased the frequency of ventricular arrhythmia. Subsequent coronary angiogram detected 99% stenosis of the right coronary artery. Ventricular arrhythmia ceased after coronary revascularization, and the patient was successfully weaned from the extracorporeal bypass circuit. The patient was discharged alive with minimal neurological impairment. We suggest that chest compression in the lateral position by two rescuers is an efficient resuscitation maneuver, and if an electrical storm is refractory to conventional CPR, extracorporeal life support should be considered in the operating-room setting. PMID- 20300779 TI - Colforsin-induced vasodilation in chronic hypoxic pulmonary hypertension in rats. AB - PURPOSE: Colforsin, a water-soluble forskolin derivative, directly activates adenylate cyclase and thereby increases the 3',5'-cyclic adenosine monophosphate (cAMP) level in vascular smooth muscle cells. In this study, we investigated the vasodilatory action of colforsin on structurally remodeled pulmonary arteries from rats with pulmonary hypertension (PH). METHODS: A total of 32 rats were subjected to hypobaric hypoxia (380 mmHg, 10% oxygen) for 10 days to induce chronic hypoxic PH, while 39 rats were kept in room air. Changes in isometric force were recorded in endothelium-intact (+E) and -denuded (-E) pulmonary arteries from the PH and control (non-PH) rats. RESULTS: Colforsin-induced vasodilation was impaired in both +E and -E arteries from PH rats compared with their respective controls. Endothelial removal did not influence colforsin induced vasodilation in the arteries from control rats, but attenuated it in arteries from PH rats. The inhibition of nitric oxide (NO) synthase did not influence colforsin-induced vasodilation in +E arteries from controls, but attenuated it in +E arteries from PH rats, shifting its concentration-response curve closer to that of -E arteries from PH rats. Vasodilation induced by 8-bromo cAMP (a cell-permeable cAMP analog) was also impaired in -E arteries from PH rats, but not in +E arteries from PH rats, compared with their respective controls. CONCLUSIONS: cAMP-mediated vasodilatory responses without beta adrenergic receptor activation are impaired in structurally remodeled pulmonary arteries from PH rats. In these arteries, endothelial cells presumably play a compensatory role against the impaired cAMP-mediated vasodilatory response by releasing NO (and thereby attenuating the impairment). The results suggest that colforsin could be effective in the treatment of PH. PMID- 20300781 TI - Camptocormia: the bent spine syndrome, an update. AB - Camptocormia, also referred to as bent spine syndrome (BSS) is defined as an abnormal flexion of the trunk, appearing in standing position, increasing during walking and abating in supine position. BSS was initially considered, especially in wartime, as a psychogenic disorder. It is now recognized that in addition to psychiatric syndromes, many cases of reducible BSS have a somatic origin related to a number of musculo-skeletal or neurological disorders. The majority of BSS of muscular origin is related to a primary idiopathic axial myopathy of late onset, appearing progressively in elderly patients. Diagnosis of axial myopathy first described by Laroche et al. is based upon CT/MRI examination demonstrating massive fatty infiltration of paravertebral muscles. The non-specific histological aspect includes an extensive endomysial fibrosis and fat tissue with irregular degenerated fibers. Weakness of the paravertebral muscles can be secondary to a wide variety of diseases generating diffuse pathologic changes in the muscular tissue. BSS can be the predominant and sometimes revealing symptom of a more generalized muscular disorder. Causes of secondary BSS are numerous. They must be carefully assessed and ruled out before considering the diagnosis of primary axial myopathy. The principal etiologies include on the one hand inflammatory myopathies, muscular dystrophies of late onset, myotonic myopathies, endocrine and metabolic myopathies, and on the other hand neurological disorders, principally Parkinson's disease. Camptocormia in Parkinsonism is caused by axial dystonia, which is the hallmark of Parkinson's disease. There is no specific pharmacologic treatment for primary axial myopathy. General activity, walking with a cane, physiotherapy, and exercises should be encouraged. Treatment of secondary forms of BSS is dependent upon the variety of the disorder generating the muscular pathology. Pharmacologic and general management of camptocormia in Parkinson's disease merge with that of Parkinsonism. Levodopa treatment, usually active on tumor rigidity and akinesia, has poor or negative effect on BSS. PMID- 20300783 TI - Protection against HIV-envelope-induced neuronal cell destruction by HIV attachment inhibitors. AB - We demonstrate that HIV attachment inhibitors (AIs) prevent HIV envelope-induced destruction of two neuronal cell lines (SH-SY5Y and BE(2)-M17) at low nanomolar concentrations. The fusion inhibitor enfuvirtide and the CCR5 inhibitors UK427,857 and TAK779 do not display protection activity, suggesting the involvement of Env/cell interaction site(s) distinct from the sites involved in the viral entry process. We surmise that by inducing conformation changes in the envelope, AIs likely obstruct novel interactions with a neuronal cell factor(s) required for induction of apoptosis. This antiretroviral class may therefore have the potential to inhibit HIV-induced neuron damage, thereby curtailing the increasing incidence of HIV-associated cognitive impairment. PMID- 20300782 TI - Spinal decompensation in degenerative lumbar scoliosis. AB - Due to the aging population, degenerative scoliosis is a growing clinical problem. It is associated with back pain and radicular symptoms. The pathogenesis of degenerative scoliosis lies in degenerative changes of the spinal structures, such as the intervertebral disc, the facet joints and the vertebrae itself. Possibly muscle weakness also plays a role. However, it is not clear what exactly causes the decompensation to occur and what determines the direction of the curve. It is known that in the normal spine a pre-existing rotation exists at the thoracic level, but not at the lumbar level. In this retrospective study we have investigated if a predominant curve pattern can be found in degenerative scoliosis and whether symptoms are predominantly present at one side relative to the curve direction. The lumbar curves of 88 patients with degenerative scoliosis were analyzed and symptoms were recorded. It was found that curve direction depended significantly on the apical level of the curve. The majority of curves with an apex above L2 were convex to the right, whereas curves with an apex below L2 were more frequently convex to the left. This would indicate that also in degenerative scoliosis the innate curvature and rotational pattern of the spine plays a role in the direction of the curve. Unilateral symptoms were not coupled to the curve direction. It is believed that the symptoms are related to local and more specific degenerative changes besides the scoliotic curve itself. PMID- 20300784 TI - Low prevalence of DNA viruses in the human endometrium and endometriosis. AB - The chronic female disease endometriosis causes debilitating pain and lowered fertility. The aetiology is unknown, but indications of an infectious agent are present. This study investigates the possible involvement of a pathogenic virus in endometriosis patients and controls. DNA was purified from biopsies and subjected to highly sensitive PCR tests detecting human papillomavirus (HPV) types, the herpes family viruses HSV-1 and -2, CMV, and EBV, and the polyomaviruses SV40, JCV, BKV, KIV, WUV, and MCV. The prevalence of pathogenic DNA viruses in the human endometrium was generally low (0-10%). The virus prevalence was found to vary slightly when comparing the endometrium of healthy women and women with endometriosis. However, these were not significant differences, and no viruses were identified in endometriotic lesions. These results do not point towards any evidence that endometriosis is caused by these viruses. PMID- 20300785 TI - Codon usage bias and recombination events for neuraminidase and hemagglutinin genes in Chinese isolates of influenza A virus subtype H9N2. AB - The representative complete neuraminidase sequences (NA) of 138 Chinese isolates and hemagglutinin sequences (HA) of 128 Chinese isolates of influenza A virus subtype H9N2 were analyzed to reveal codon usage bias and recombination events. A plot of the effective number of codons (ENC) against G + C context at the third position of the codons (ENC-plot) and correlation analysis demonstrated that mutational pressure is the main factor determining the codon usage bias in the H9N2 subtype. The high ENC values (51.31 for NA and 48.83 for HA) indicated that the codon usage bias in Chinese H9N2 isolates was very low. Plots of correspondence analysis and an ENC plot indicated that the HA and NA genes had different codon usage bias. Recombination analysis revealed two possible recombination events for HA and NA gene sequences in the Chinese isolates. Subsequent phylogenetic analysis further supported the validity of these recombination events. In addition, one false-positive recombinant for HA gene was found, which may have been derived from contamination during PCR amplification. PMID- 20300786 TI - Tanshinone IIA enhances BMP-2-stimulated commitment of C2C12 cells into osteoblasts via p38 activation. AB - In this study, we demonstrate a stimulatory effect of tanshinone IIA isolated from the root of Salvia miltiorrhiza on the commitment of bi-potential mesenchymal precursor C2C12 cells into osteoblasts in the presence of bone morphogenetic protein (BMP)-2. At low concentrations, tanshinone IIA enhanced BMP 2-stimulated induction of alkaline phosphatase (ALP), an early phase biomarker of osteoblast differentiation, and mRNA expression of BMPs. ALP induction was inhibited by the BMP antagonist noggin, suggesting that tanshinone IIA enhances the osteogenic activity of BMP signaling. Furthermore, considering the tanshinone IIA-mediated enhancement of BMP-2-stimulated Smad-Runx2 activities, tanshinone IIA could enhance the osteogenic activity of BMP-2 via acceleration of Smad-Runx2 activation. Additionally, pharmacologic inhibition studies suggest the possible involvement of p38 in the action of tanshinone IIA. The p38 inhibitor SB202190 strongly and dose-dependently inhibited tanshinone IIA-enhanced ALP induction. SB202190 also dose-dependently inhibited the tanshinone IIA-induced p38 activation and combined tanshinone IIA-BMP-2-induced Smad activation. In conclusion, tanshinone IIA enhances the commitment of C2C12 cells into osteoblasts and their differentiation through synergistic cross talk between tanshinone IIA-induced p38 activation and BMP-2-induced Smad activation. These activations could subsequently induce the activation of Runx2, which induces osteogenesis via regulation of the osteogenic factors BMP and ALP expression. PMID- 20300787 TI - Utilization of amino acids by bacteria from the pig small intestine. AB - This study determined the utilization of amino acids (AA) by bacteria from the lumen of the pig small intestine. Digesta samples from different segments of the small intestine were inoculated into media containing 10 mmol/L each of select AA (L-lysine, L-threonine, L-arginine, L-glutamate, L-histidine, L-leucine, L isoleucine, L-valine, L-proline, L-methionine, L-phenylalanine or L-tryptophan) and incubated for 24 h. The previous 24-h culture served as an inoculum for a subsequent 24-h subculture during each of 30 subcultures. Results of the in vitro cultivation experiment indicated that the 24-h disappearance rates for lysine, arginine, threonine, glutamate, leucine, isoleucine, valine or histidine were 50 90% in the duodenum, jejunum or ileum groups. After 30 subcultures, the 24-h disappearance rates for lysine, threonine, arginine or glutamate remained greater than 50%. The denaturing gradient gel electrophoresis analysis showed that Streptococcus sp., Mitsuokella sp., and Megasphaera elsdenii-like bacteria were predominant in subcultures for utilizing lysine, threonine, arginine and glutamate. In contrast, Klebsiella sp. was not a major user of arginine or glutamate. Furthermore, analysis of AA composition and the incorporation of AA into polypeptides indicated that protein synthesis was a major pathway for AA metabolism in all the bacteria studied. The current work identified the possible predominant bacterial species responsible for AA metabolism in the pig small intestine. The findings provide a new framework for future studies to characterize the metabolic fate of AA in intestinal microbes and define their nutritional significance for both animals and humans. PMID- 20300788 TI - Gluten T cell epitope targeting by TG3 and TG6; implications for dermatitis herpetiformis and gluten ataxia. AB - Transglutaminase 2 (TG2) is well characterized as the main autoantigen of celiac disease. The ability of TG2 to deamidate and crosslink gluten peptides is essential for the gluten-dependent production of TG2 specific autoantibodies. In patients with primarily extraintestinal manifestation of gluten sensitivity the repertoire of autoantibodies may be different. In dermatitis herpetiformis (DH), TG3 appears to be the target autoantigen whereas in gluten ataxia (GA) autoantibodies reactive with TG6 are present. A functional role for TG3 and TG6 in these diseases has yet to be described. It is also not known whether these enzymes can use gluten peptides implicated in the pathology as substrates. We here report that similar to TG2, TG3 and TG6 can specifically deamidate gluten T cell epitopes. However, the fine specificities of the enzymes were found to differ. TG2 can form covalent complexes with gluten by iso-peptide and thioester bonds. We found that both TG3 and TG6 were able to complex with gluten peptides through thioester linkage although less efficiently than TG2, whereas TG6 but not TG3 was able to form iso-peptide linked complexes. Our findings lend credence to the notion that TG3 and TG6 are involved in the gluten-induced autoimmune responses of DH and GA. PMID- 20300789 TI - Use of the Burrows-Wheeler similarity distribution to the comparison of the proteins. AB - In this paper, we present an approach based on Burrows-Wheeler transform to compare the protein sequences. The strings representing amino acid sequences do not reflect the chemical physical properties better, and it is very hard to extract any key features by reading these long character strings directly. The use of the Burrows-Wheeler similarity distribution needs a suitable representation which can reflect some interesting properties of the proteins. For the comparison of the primary protein sequences we convert the protein sequences into digital codes by the Ponnuswamy hydrophobicity index, and for the comparison of the structure of the proteins we adjust the topology of protein structure strings, which are simple but useful representation of the secondary structure of proteins to match the Burrows-Wheeler similarity distribution. At last, some experiments show that the approach proposed in this paper is a powerful and useful tool for the comparison of proteins. PMID- 20300791 TI - Inter-individual and age differences in exploration, neophobia and problem solving ability in a Neotropical raptor (Milvago chimango). AB - Animal innovations have far-reaching ecological and evolutionary consequences. The occurrence and persistence of an innovation require several processes, including exploration, social and asocial learning, and low neophobia. In addition, the identity of the innovator may determine how these new behaviours are socially transmitted. Taking into account inter-individual and age differences, we investigated three correlates of animal innovation: object exploration, neophobia level and novel problem-solving ability in an opportunistic generalist raptor, the Chimango Caracara (Milvago chimango). Eighteen individuals (7 adults and 11 juveniles) were caught during the non breeding period and housed in individual cages in outdoor aviaries. Each bird was given three tests: exploration, neophobia and problem-solving. Individuals differed in their response to novel situations both within and between age groups. Most of the juveniles were more explorative and had a lower neophobic response to a strange object than adult birds, but both age groups were able to solve a novel problem when given a food reward. In juveniles, neophobia level and problem-solving performance were inversely related; however, we found no relationship between these behaviours in adults. Exploration did not correlate with neophobia or problem-solving ability for either age group. This research is one of the few studies exploring the inter-individual and age differences in behavioural innovation and their correlates in a bird of prey. The explorative tendency, low neophobia and ability to innovate showed by M. chimango may be advantageous for this generalist and opportunistic raptor and might be some of the factors underlying its ecological success. PMID- 20300790 TI - Inhibition of osteoclastogenesis by prolyl hydroxylase inhibitor dimethyloxallyl glycine. AB - Studies examining the effects of hypoxia upon osteoclast biology have consistently revealed a stimulatory effect; both osteoclast differentiation and resorption activity have been shown to be enhanced in the presence of hypoxia. In the present study we examined the effects of the hypoxia mimetics dimethyloxallyl glycine (DMOG) and desferrioxamine (DFO) upon osteoclastogenesis. In contrast to hypoxia, our studies revealed a dose-dependent inhibition of osteoclast formation from macrophages treated with DMOG and DFO. Moreover, expression of a constitutively active form of hypoxia-inducible factor 1alpha (HIF-1alpha) did not enhance osteoclastogenesis and actually attenuated the differentiation process. DMOG did not affect cell viability or receptor activator of nuclear factor kappaB ligand (RANKL)-dependent phosphorylation of mitogen-activated protein (MAP) kinases. However, RANKL-dependent transcription of tartrate resistant acid phosphatase (TRAP) was reduced in the presence of DMOG. Additionally, DMOG promoted transcription of the pro-apoptotic mediator B-Nip3. These studies suggest that a hypoxia-responsive factor other than HIF-1alpha is necessary for enhancing the formation of osteoclasts in hypoxic settings. PMID- 20300792 TI - The spectrum of GNE mutations: allelic heterogeneity for a common phenotype. AB - Hereditary inclusion body myopathy (IBM2) was mainly reported in Middle Eastern Jewish patients. Distal myopathy with rimmed vacuoles has been described as a worldwide distributed distal myopathy. Both diseases are caused by mutations of the UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase (GNE) gene. Herein we report two patients: an Egyptian Muslim patient with the "common" Middle Eastern mutation (M712T), rarely described in non-Jewish patients; and an Italian patient carrying a novel GNE mutation (L179F) in the epimerase domain. Our patients share common clinical and histopathological features, with some interesting aspects. The first patient presented a clinical deterioration during her first pregnancy confirming that an increased requirement of sialic acid during pregnancy may trigger a clinical worsening. The second patient showed a slowly progressive deterioration, different from other patients carrying mutations in the epimerase domain, who had a severe and rapid progression. PMID- 20300793 TI - Subacute cognitive disorders as initial presentation of intravascular lymphoma: a case report and review of literature. AB - Intravascular lymphoma is a rare subtype of diffuse large B cell lymphoma, characterized by proliferation of mature B cells within the lumina of small and medium vessels of many organs, without parenchymal involvement. The clinical phenotype is extremely variegated; moreover, neurological symptoms such as encephalopathy and focal neurological deficits occur and often coincide with disease's debut. We described the clinical course of a patient with intravascular diffuse large B cell lymphoma presented with subacute cognitive decline without focal signs, later associated to aspecific general symptoms that rapidly evolved to a severe inexplicable encephalopathy accompanied to systemic failure. PMID- 20300795 TI - The trend of drug-resistant Streptococcus pneumoniae from nasopharynx of children. AB - We investigated the trend of the carriage of drug-resistant Streptococcus pneumoniae in nasopharynx of children. The 202 isolates from pediatric outpatients and their previous antibiotic use was investigated from 2004 to 2006. The total rate of patients medicated with antibiotics was 47.5%, a 6.9% decrease compared with our previous study performed from 2001 to 2003. There were 56 (27.7%) penicillin-susceptible, 83 (41.1%) penicillin-intermediate, and 63 (31.2%) penicillin-resistant strains by the susceptibility breakpoints used during the previous study period. There were 196 (97%) susceptible, 5 (2.5%) intermediate, and 1 (0.5%) resistant strains by breakpoints in this study, which were introduced in 2008 by the Clinical Laboratory and Standards Institute. The rate of strains with a single altered pbp gene was 21.8% (44), with 2 altered pbp genes was 21.8% (31), and with 3 altered pbp genes was 53.5% (108). The total rate of strains with altered pbp gene(s) was 90.1% (183). We found the emergence of strains with pbp1a and 2b and the higher rate of strains with pbp2x. There was obvious association between amoxicillin use and the carriage of altered pbp gene(s). These results might suggest that amoxicillin was not a safe alternative to prevent the emergence of resistant strains. We need to reassess a beneficial approach for the treatment of pediatric outpatients. PMID- 20300794 TI - Nervous system and Fabry disease, from symptoms to diagnosis: damage evaluation and follow-up in adult patients, enzyme replacement, and support therapy. AB - The X-linked genetic Fabry disease causes multiorgan lesions due to intracellular storage of the substrate globotriaosylceramide. Neurological involvement ranges from painful, small fiber neuropathy to cerebrovascular disorders to multifocal aggressive forms. Disease identification through proper differential diagnosis and timely assessment of organ damage should guide a careful treatment planning. Mainstay treatment, include enzyme replacement and support therapy. Neurologists have a pivotal role in early instrumental and clinical detection of organ damage. A panel of experts has developed a set of consensus recommendations to guide the approach of neurologists to Fabry disease. PMID- 20300796 TI - The target hemoglobin in non-dialysis CKD: still a matter for debate? PMID- 20300797 TI - Detecting columnar deformations in a supermesogenic octapode by proton NMR relaxometry. AB - We used proton ( (1)H nuclear magnetic relaxation (NMR) dispersions to study the molecular dynamics in the isotropic phase and mesophases (nematic and columnar hexagonal) of a supermesogenic octapode formed by laterally connecting calamitic mesogens to an inorganic silsesquioxane cube through flexible spacers. The dispersions of the spin-lattice relaxation time (T(1)) are interpreted through relaxation mechanisms used for the study of molecular dynamics in low-molar-mass liquid crystals but adapted to the case of liquid crystalline supermolecules. At high frequencies (above 10MHz) the behaviour of the T(1) with the Larmor frequency is similar for all phases and is ascribed to local reorientations and/or rotations. At intermediate and low frequencies (below 10MHz) our results show notable differences in the T(1) behaviour with respect to the mesophases. The nematic (N) and isotropic (Iso) phases' low-frequency results are similar and are interpreted for both phases in terms of order director fluctuations (ODF), revealing that even in the isotropic phase local nematic order is detected by proton NMR relaxometry. Local nematic order in the Iso phase is interpreted in terms of the presence of nematic cybotactic clusters induced by the interdigitation of mesogens that is promoted by the silsesquioxane octapode molecular structure. In the columnar hexagonal (Col (h) phase, the T(1) dispersions show that elastic columnar deformations (ECD) dominate the nuclear magnetic relaxation below 10MHz. This result shows that the columnar packing of the octapode clearly restricts the collective fluctuations of the mesogenic units inspite of their local nematic order. PMID- 20300798 TI - Autonomic failure in a HIV-infected patient. AB - We present a case report of severe autonomic failure in a 43-year-old well controlled HIV patient. Clinical and pharmacological autonomic function testing supported the diagnosis of peripheral autonomic failure. Simple physiological manoeuvres substantially improved symptoms. PMID- 20300799 TI - The social determinants of what? PMID- 20300800 TI - Causal connections between water quality and land use in a rural tropical island watershed: rural tropical island watershed analysis. AB - We examined associations between riparian canopy cover, presence or absence of cattle, rainfall, solar radiation, month of year, dissolved oxygen, turbidity, salinity, and Enterococcus concentrations in riparian surface soils with Enterococcus geometric mean in-stream water concentrations at Waipa watershed on the north side of the Hawaiian island Kaua'i. Each 1% decrease in riparian canopy cover was associated with a 4.6 most probable number (MPN)/100 ml increase of the geometric mean of Enterococcus in stream water (P < 0.05). Each unit decrease in salinity (ppt) was associated with an increase of Enterococcus by 68.2 MPN/100 ml in-stream water geometric mean concentrations (P < 0.05). Month of year was also associated with increases in stream water Enterococcus geometric mean concentrations (P < 0.05). Reducing riparian canopy cover is associated with Enterococcus increases in stream water, suggesting that decreasing riparian vegetation density could increase fecal bacteria surface runoff. PMID- 20300801 TI - Performance of the IEF-MST solvation continuum model in the SAMPL2 blind test prediction of hydration and tautomerization free energies. AB - The IEF-MST continuum solvation model is used to predict the hydration free energies and tautomeric preferences of a set of multifunctional compounds compiled as a blind test for computational solvation methods in the SAMPL2 contest. Computations of hydration free energies was performed using both HF/6 31G(d) and B3LYP/6-31G(d) versions of the IEF-MST model. For tautomeric preferences, the IEF-MST data was combined with the gas phase free energy differences predicted at different levels of theory ranging from MP2/6-31+G(d) to MP2/CBS+[CCSD-MP2/6-31+G(d)] levels. Comparison with the experimental data provided for hydration free energies yields a root-mean square deviation (rmsd) close to 2.3 kcal/mol, which is quite remarkable, especially considering the reduced set of training compounds used in the parametrization of the IEF-MST method. With regard to tautomerism, the lowest error in the prediction of the relative stabilities between tautomers in solution is obtained by combining MP2/CBS+[CCSD-MP2/6-31+G(d)] results with IEF-MST hydration free energies, yielding a rmsd of ca. 3.4 kcal/mol. The results illustrate the delicate balance that must be kept between the intrinsic relative stabilities in the gas phase and the differential hydration preferences in order to obtain an accurate description of the prototropic tautomerism in bioorganic compounds. PMID- 20300803 TI - pH-sensitive multi-PEGylated block copolymer as a bioresponsive pDNA delivery vector. AB - PURPOSE: A reversibly-PEGylated diblock copolymer, poly(aspartate-hydrazide poly(ethylene glycol))-block-poly(aspartate-diaminoethane) (p[Asp(Hyd-PEG)]-b p[Asp(DET)]) was reported here for enhanced gene transfection and colloidal stability. The diblock copolymer possessed a unique architecture based on a poly(aspartamide) backbone. The first block, p[Asp(Hyd)], was used for multi-PEG conjugations, and the second block, p[Asp(DET)], was used for DNA condensation and endosomal escape. METHODS: p[Asp(Hyd-PEG)]-b-p[Asp(DET)] was synthesized and characterized by (1)H-NMR. Polyplexes were formed by mixing the synthesized polymers and pDNA. The polyplex size, zeta-potential, and in vitro transfection efficiency were determined by dynamic light scattering, zeta-potential measurements, and luciferase assays, respectively. pH-dependent release of PEG from the polymer was monitored by cationic-exchange chromatography. RESULTS: The polyplexes were 70-90 nm in size, and the surface charge was effectively shielded by a PEG layer. The transfection efficiency of the reversibly PEGylated polyplexes was confirmed to be comparable to that of the non-PEGylated counterparts and 1,000 times higher than that of the irreversibly PEGylated polyplexes. PEG release was demonstrated to be pH-sensitive. Fifty percent of the PEG was released within 30 min at pH 5, while the polymer incubated at pH 7.4 could still maintain 50% of PEG after 8 h. CONCLUSION: The reversibly PEGylated polyplexes were shown to maintain polyplex stability without compromising transfection efficiency. PMID- 20300802 TI - Two-layered dissolving microneedles for percutaneous delivery of peptide/protein drugs in rats. AB - PURPOSE: Feasibility study of two-layered dissolving microneedles for percutaneous delivery of peptide/proteins using recombinant human growth hormone (rhGH) and desmopressin (DDAVP). METHODS: Two-layered dissolving microneedles were administered percutaneously to the rat skin. Plasma rhGH and DDAVP concentrations were measured by EIA and LC/MS/MS. In vivo dissolution and diffusion rates of drugs in the skin were studied using tracer dyes, lissamine green B (LG) for rhGH and evans blue (EB) for DDAVP. Diffusion of drugs vertically into the skin was studied using FITC-dextran (MW = 20 kDa)-loaded dissolving microneedles. Stability experiments were performed at -80 degrees C and 4 degrees C. RESULTS: The absorption half-lives, t (1/2a), of rhGH and DDAVP from dissolving microneedles were 23.7 +/- 4.3-28.9 +/- 5.2 and 14.4 +/- 2.9-14.1 +/- 1.1 min; the extents of bioavailability were 72.8 +/- 4.2-89.9 +/- 10.0% and 90.0 +/- 15.4-93.1 +/- 10.3%, respectively. LG and EB disappeared from the administered site within 2 h and 3 h after administration. Five green fluorescein spots were detected at 15 s and enlarged transversally at 30 s. FITC-dextran was delivered into the microcapillaries at 5 min and 10 min. The rhGH and DDAVP were stable in dissolving microneedles for one month at -80 degrees C and 4 degrees C. CONCLUSIONS: Results suggest that the two-layered dissolving microneedles are useful as an immediate-release transdermal DDS for peptide/protein drugs. PMID- 20300804 TI - Multi-component polymeric system for tumour cell-specific gene delivery using a universal bungarotoxin linker. AB - PURPOSE: A new universal tool for specific, non-covalent and non-destructive attachment of a recombinant antibody fragment to a polymer-modified adenovirus has been utilised to regulate the tropism of adenoviral gene delivery vector. METHODS: We have prepared a multivalent reactive N-(2 hydroxypropyl)methacrylamide-based copolymer (PHPMA) bearing an alpha bungarotoxin-binding peptide (BTXbp). The copolymer was used for covalent surface modification of adenoviral vectors (Ad). The alpha-bungarotoxin protein (BTX) has a nanomolar binding affinity for BTXbp, allowing non-covalent linkage of BTX fusion proteins. A single chain variable fragment of anti-PSMA antibody bearing BTX (scFv-BTX) binding to the prostate-specific membrane antigen (PSMA) was conjugated with the copolymer-coated adenovirus to enable specific infection of prostate cancer cells via PSMA receptors. RESULTS: As shown by ELISA, the copolymer-coated virus exhibited much reduced binding to anti-Ad antibodies. Infection of PC-3 and LNCaP prostate cancer cells was ~100-fold less efficient with copolymer-coated Ad than with un-modified Ad. Conjugation of scFv-BTX with Ad-PHPMA-BTXbp led to 5-10-fold restoration of infection in PSMA-positive LNCaP cells. In PSMA-negative PC-3 cells, the conjugation of scFv-BTX with Ad-PHPMA BTXbp gave no enhancement of infection. CONCLUSIONS: We have shown that the presented Ad-PHPMA-BTXbp/scFv-BTX system can be used as a universal tool for a receptor-specific virotherapy. PMID- 20300806 TI - Suppression of microRNA accumulation via RNA interference in Arabidopsis thaliana. AB - MicroRNAs (miRNAs) are key regulatory molecules in plants. These small RNAs are processed in the nucleus from longer precursor transcripts that form distinct secondary structures. The miRNAs target specific messenger RNAs (mRNAs) and consequently down-regulate gene expression. The importance of these regulatory molecules is wide-ranging, however, few loss-of-function mutants have been identified in miRNA genes and understanding the biology of miRNA-target pairings has largely depended upon creating alterations in the sequences of the target genes. Here we demonstrate using Arabidopsis thaliana, that it is possible to use RNA interference (RNAi) to suppress accumulation of miRNAs. Significantly reduced accumulation of miR163 and miR171a was achieved using hairpin RNAi constructs that were designed to target both the primary miRNA transcripts and their promoters. The presence of DNA methylation in the targeted promoter regions suggests that inhibition of transcription of the miRNA precursors is responsible. Reduction of miRNA accumulation resulted in an increase in accumulation of the mRNA targets of these miRNAs. This demonstrates that knock-down of miRNA expression can be achieved, thereby providing a straightforward approach for disrupting miRNA-target pairings and studying miRNA functions. PMID- 20300805 TI - PCS-based structure determination of protein-protein complexes. AB - A simple and fast nuclear magnetic resonance method for docking proteins using pseudo-contact shift (PCS) and (1)H(N)/(15)N chemical shift perturbation is presented. PCS is induced by a paramagnetic lanthanide ion that is attached to a target protein using a lanthanide binding peptide tag anchored at two points. PCS provides long-range (approximately 40 A) distance and angular restraints between the lanthanide ion and the observed nuclei, while the (1)H(N)/(15)N chemical shift perturbation data provide loose contact-surface information. The usefulness of this method was demonstrated through the structure determination of the p62 PB1-PB1 complex, which forms a front-to-back 20 kDa homo-oligomer. As p62 PB1 does not intrinsically bind metal ions, the lanthanide binding peptide tag was attached to one subunit of the dimer at two anchoring points. Each monomer was treated as a rigid body and was docked based on the backbone PCS and backbone chemical shift perturbation data. Unlike NOE-based structural determination, this method only requires resonance assignments of the backbone (1)H(N)/(15)N signals and the PCS data obtained from several sets of two-dimensional (15)N heteronuclear single quantum coherence spectra, thus facilitating rapid structure determination of the protein-protein complex. PMID- 20300807 TI - Impaired antigen processing and presentation machinery is associated with immunotolerant state in chronic hepatitis B virus infection. AB - BACKGROUND AND AIMS: The mechanism of hepatitis B virus (HBV)-specific T cell hyporesponsiveness in hepatitis Be antigen (HBeAg)-positive subjects is not well understood. Inefficient antigen processing and transport to major histocompatibility complex class I molecules, namely due to low molecular weight protein (LMP) 2 and 7 and transporter associated with antigen processing (TAP) 1 and 2 genes could be playing a role. PATIENTS AND METHODS: Forty patients with chronic hepatitis B (CHB) infection, hepatitis B surface antigen, and HBeAg positive; 26 with raised (Gr. I) and 14 with persistently normal ALT levels (Gr. II) and 11 healthy controls (Gr. III) were studied. Total RNA was isolated from peripheral blood mononuclear cells and mRNA expression of TAP1, TAP2, LMP2, and LMP7 genes was analyzed by semi-quantitative reverse transcriptase-polymerase chain reaction method. Gamma interferon (IFN-gamma) and tumor necrosis factor alpha (TNF-alpha) levels were quantified by enzyme-linked immunosorbent assay (ELISA) using log-log and linear graphs, respectively. RESULTS: Group II CHB patients had significantly lower mRNA expression for TAP1 (p = 0.003) and LMP2 (p = 0.002) genes as compared to Gr. I patients. The mRNA expression of TAP2 and LMP7 genes was comparable between the groups. However, expression of TAP1 (p = 0.02), TAP2 (p = 0.035), and LMP2 (p = 0.041) was found to be significantly higher in Gr. III subjects compared to Gr. I and Gr. II patients. In Gr. I and II, the IFN-gamma {s54.2{9.4-165} pg/ml), (59.5{28.5-110} pg/ml)}, and TNF-alpha {12.0 (8.0-23.2)},{10.8(6.2-20.8)} pg/ml levels were comparable but were significantly (p = 0.00,0.004, respectively) higher than Gr. III subjects. CONCLUSIONS: Low expression of TAP1 and LMP2 suggests an important role of these genes in defective viral antigen processing in immune tolerant state of CHB patients. Higher IFN-gamma and TNF-alpha production in CHB are probably enough to potentiate liver injury but not enough to clear the chronic HBV infection. These novel observations could pave way for new therapeutic strategies for immune restoration in CHB infected patients. PMID- 20300808 TI - Utilization of the Native American Talking Circle to teach incident command system to tribal community health representatives. AB - The public health workforce is diverse and encompasses a wide range of professions. For tribal communities, the Community Health Representative (CHR) is a public health paraprofessional whose role as a community health educator and health advocate has expanded to become an integral part of the health delivery system of most tribes. CHRs possess a unique set of skills and cultural awareness that make them an essential first responder on tribal land. As a result of their distinctive qualities they have the capability of effectively mobilizing communities during times of crisis and can have a significant impact on the communities' response to a local incident. Although public health emergency preparedness training is a priority of federal, state, local and tribal public health agencies, much of the training currently available is not tailored to meet the unique traits of CHRs. Much of the emergency preparedness training is standardized, such as the Federal Emergency Management Agency (FEMA) Training Programs, and does not take into account the inherent cultural traditions of some of the intended target audience. This paper reports on the use of the Native American Talking Circle format as a culturally appropriate method to teach the Incident Command System (ICS). The results of the evaluation suggest the talking format circle is well received and can significantly improve the understanding of ICS roles. The limitations of the assessment instrument and the cultural adaptations at producing changes in the understanding of ICS history and concepts are discussed. Possible solutions to these limitations are provided. PMID- 20300809 TI - Peer knowledge and roles in supporting access to care and treatment. AB - People living with HIV (PLWHIV) have been involved in the continuum of HIV care since the early days of the epidemic providing education and prevention services. There is a growing interest in utilizing HIV positive peers to support access to care and treatment, but little is known about the range of roles these peers perform and what they need to know to do this work. This study of 186 HIV positive peers currently providing community health services in eight states found that peers perform a wide range of roles, including assistance with care and treatment, emotional support, and service referrals. Over 80% discussed medications with clients. On average, experienced peers provided correct responses to 73% of questions about HIV and AIDS, and 65% of questions about the appropriate role of a peer. Peers living with HIV for more than 5 years, in paid employment with more than a high school education had higher HIV knowledge scores than volunteers. Higher education, length of time living with HIV, age and speaking English as the primary language were associated with higher peer knowledge scores. This study suggests that we cannot assume that peers already working in the field are fully knowledgeable about HIV care and treatment or peer roles. It is important to address gaps in knowledge through continuing education and to create common standards for the training and skills that peers who work in community health settings need to have. PMID- 20300810 TI - Hepatitis B prevalence among Asian Americans in Michigan: an assessment to guide future education and intervention strategies. AB - Free HBV (hepatitis B virus) screening was offered at 8 health fairs to Asian Americans in Southeast and West Michigan for two and a half years as a community service to study the prevalence of hepatitis B among Asian Americans in Michigan as a first step in reducing the incidence of hepatitis B. The screening included a 4 ml blood sample and a questionnaire assessing demographics and family history of hepatitis B; tests included the HBV surface antigen and antibody. 567 people participated in the study. About 6% of the participants had chronic hepatitis B (HBV carriers), 54% had the antibody (either had the disease before or were vaccinated) and 40% had no antibody or antigen (never infected by HBV and should be vaccinated to get protection). More than 95% of the participants were immigrants. Participants indicated in the family history that 10% had relatives with hepatitis B, 5% with liver cirrhosis, and 3% with liver cancer. Results of our screening supported our hypothesis that prevalence of hepatitis B among Asian Americans in Michigan would be similar to that in Asian Americans on the East and West coasts. We need to develop a strategy in Michigan to address this disease. In conducting this study, it was noticed that there was still resistance by Asian Americans to participate in clinical studies. An education intervention that is delivered in native Asian languages and in a culturally sensitive manner is needed to effectively raise awareness of hepatitis B among Asian Americans. PMID- 20300811 TI - Production of reactive oxygen species by the mitochondrial electron transport chain in Drosophila melanogaster. AB - Mitochondrial free radicals and in particular mitochondrial Reactive Oxygen Species (mtROS) are considered to be totally or partially responsible for several different diseases including Parkinson, diabetes or cancer. Even more importantly, mtROS have also been proposed as the main driving force behind the aging process. Thus, in the last decade, there has been a growing interest in the role of free radicals as signalling molecules. Collectively this makes understanding mechanisms controlling free radical production extremely important. There is extensive published literature on mammalian models (essentially rat, mouse and guinea pig) however; this is not the case in Drosophila melanogaster. Drosophila is an excellent model to study different physiological and pathological processes. Additionally a robust method to study mtROS is extremely useful. In the present article, we describe a simple--but extremely sensitive- method to study mtROS production in Drosophila. We have performed various experiments to determine which specific respiratory complexes produce free radicals in the electron transport chain of Drosophila melanogaster. Complex I is the main generator of ROS in Drosophila mitochondria, leaking electrons either in the forward or reverse direction. The production of ROS during reverse electron transport can be prevented either by rotenone or by the oxidation of NADH by complex I. These results clearly show that Drosophila mitochondria function in a very similar way to mammalian mitochondria, and therefore are a very relevant experimental model for biochemical studies related to ageing. PMID- 20300812 TI - Effects of Ginkgo biloba extract on heart and liver mitochondrial functions: mechanism(s) of action. AB - Though extracts of Ginkgo biloba leaves (GBE) have a wide pharmacological application, little is known about GBE effects on mitochondria. In this work, effects of ethanolic GBE on the respiration of isolated rat heart and liver mitochondria were investigated. We found that GBE stimulates the pyruvate + malate-dependent State 2 respiration of heart mitochondria and decreases mitochondrial membrane potential. Uncoupling effect of GBE was found to be due to its protonophoric action and is likely to be mediated by the ATP/ADP-translocator and uncoupling proteins. The effect of GBE was less in liver than in heart mitochondria. State 3 respiration of heart mitochondria was slightly stimulated at low and depressed at higher GBE concentrations. Inhibition of State 3 respiration of heart mitochondria was not relieved by uncoupler indicating that GBE may inhibit the respiratory chain complexes or the substrate transport. However, Complex IV of the respiratory chain was not inhibited by GBE. H(2)O(2) generation was attenuated by low concentration of GBE probably due to mild uncoupling. The data suggest that mild but not severe uncoupling activity of GBE may be important in providing pharmacological protection of cellular functions in pathological situations. PMID- 20300813 TI - Perinatal depression and birth outcomes in a Healthy Start project. AB - Given the risk of adverse perinatal outcomes associated with a depressive disorder, the Health Resources and Services Administration's (HRSA) Maternal and Child Health Bureau (MCHB) from 2001-2005 devoted resources through the Federal Healthy Start Initiative to screen pregnant women for depression and link them with services. In this report, we present the evaluation of a program that screened for depression and provided services for women with depressive symptoms or psychiatric distress in pregnancy to assess whether the program was associated with a reduction in babies born low birth weight, small for gestational age, or preterm. The program impact was examined among 1,100 women in three cohorts enrolled from 2001-2005 that included: (1) subjects recruited prior to the inception of the Healthy Start Initiative; (2) subjects enrolled in the Healthy Start Initiative; and (3) a comparison group recruited during the project period but not enrolled in the Healthy Start Initiative. After adjustment for covariates, women with probable depression were over one and a half times more likely to give birth to a preterm baby than non depressed women. Neither adjusted nor unadjusted risks for delivery of preterm, low birth weight or small for gestational age infants were significantly lower for women enrolled in Healthy Start as compared to women not enrolled in Healthy Start. However, regardless of enrollment in Healthy Start, women who delivered babies after the Healthy Start program began were 85% less likely to deliver preterm babies than women giving birth before the program began. Depression status conferred increased risk of adverse birth outcomes, results that were not altered by participation in the Healthy Start program. We cannot exclude the possibility that the community activities of the Healthy Start program promoted increased attention to health issues among depressed women and hence enhance birth outcomes. PMID- 20300814 TI - The effect of parity on cause-specific mortality among married men and women. AB - The objective of this study was to examine mortality differentials among men and women by parity for deaths from cardio-vascular disease (CVD), cancer and other causes. The census-based Israel Longitudinal Mortality Study II (1995-2004) was used to identify 71,733 married men and 62,822 married women (45-89 years). During the 9-year follow-up period, 19,347 deaths were reported. Cox proportional hazard models adjusted for age, origin, and social class were used. A non-linear association between parity and CVD mortality was detected for men and women. Excess CVD mortality risks were observed among middle-aged women with no children (hazard ratio [HR] 2.43, 95% confidence interval [CI] 1.49, 3.96) and among middle-aged women and men with 8+ children (HR(women) 1.64, CI 1.02, 2.65; HR(men) 1.40, CI 1.01, 1.93) compared to those with two children. No clear pattern of association between cancer mortality and parity was apparent for men. Elderly women with 8+ children showed reduced mortality risks from reproductive cancers (HR 0.22, CI 0.05, 0.91). Similar parity-related mortality patterns were observed for men and women for deaths from CVD and other causes indicating biosocial pathways. The association between parity and cancer mortality differed by gender, age and type of cancer. PMID- 20300815 TI - Effects of oral glucocorticoid therapy on CD4+CD25+CD127- and CD4+CD25high T cell levels in asthmatic patients. AB - Our purpose was to evaluate the effects of short-term oral glucocorticoid (GC) treatment on frequencies of T cells with putative regulatory phenotype (namely, CD4+CD25+CD127- and CD4+CD25high) in patients with asthma exacerbations. In addition, we sought to determine frequencies of above T cell subsets in adult asthmatic patients in relation to disease severity and different treatment regimens. The analysis was performed in 62 patients with different stages of asthma and ten healthy controls. Polychromatic flow cytometry was applied to delineate T cells with CD4+CD25+CD127- and CD4+CD25high phenotype. Exhaled nitric oxide analysis was used to assess allergic airway inflammation. Levels of neither CD4+CD25+CD127- nor CD4+CD25high T cells were significantly altered after 7-day oral GC treatment. Importantly, there were no detectable differences in frequencies of those cells among studied groups of asthmatics with different severity of disease and healthy controls. Moreover, levels of CD4+CD25+CD127- and CD4+CD25high T cells in asthmatic patients were not correlated to exhaled nitric oxide concentrations. Our data indicate that neither effects of average doses of oral GC treatment nor disease severity are related to changes in frequencies of CD4+CD25+CD127- and CD4+CD25high T cells in adult asthmatic patients. PMID- 20300816 TI - The cognitive interview for eyewitnesses with autism spectrum disorder. AB - The cognitive interview (CI) is one of the most widely accepted forms of interviewing techniques for eliciting the most detailed, yet accurate reports from witnesses. No research, however, has examined its effectiveness with witnesses with autism spectrum disorder (ASD). Twenty-six adults with ASD and 26 matched typical adults viewed a video of an enacted crime, and were then interviewed with either a CI, or a structured interview (SI) without the CI mnemonics. Groups did not differ on the quantity or quality of their reports when interviewed with a SI, however, when interviewed with a CI the ASD group was significantly less accurate. Findings indicate that investigative professionals should be cautious in relying on the CI to interview witnesses with ASD. PMID- 20300817 TI - Memory awareness for faces in individuals with autism. AB - Little is known regarding metacognition in individuals with autism. Specifically, it is unclear how individuals with autism think about their own mental states. The current study assessed memory awareness during a facial recognition task. High-functioning children (M = 13.1 years, n = 18) and adults (M = 27.5 years, n = 16) with autism matched with typically developing children (M = 14.3 years, n = 13) and adults (M = 26.9 years, n = 15) were tested. Children with autism demonstrated less accurate memory awareness for faces and less reliable differentiation between their confidence ratings compared to typically developing children. Subtle impairments in memory awareness for faces were also evident in adults with autism. Results indicate that broader metacognitive deficits may exist in individuals with autism, possibly contributing to other known impairments. PMID- 20300818 TI - Does parental education have a moderating effect on the genetic and environmental influences of general cognitive ability in early adulthood? AB - Hereditary influences account for a substantial proportion of the variance in many cognitive abilities. However, there is increasing recognition that the relative importance of genetic and environmental influences may vary across different socioeconomic levels. The overall goal of the present study was to examine whether parental education has a moderating effect on genetic and environmental influences of general cognitive ability in early adulthood (age 19.6 +/- 1.5). Participants were 5,955 male twins from the Vietnam Era Twin (VET) Registry. Significant effects of parental education on mean level of general cognitive ability scores were found, but a model without moderating effects of parental education on genetic or environmental influences on cognitive scores proved to be the best fitting model. Some, but not all, previous studies have found significant moderating effects; however, no consistent pattern emerged that could account for between-study differences regarding moderating effects on genetic and environmental influences. PMID- 20300819 TI - First same-sex partner and the internet. AB - The present study examined the first episode of anal intercourse of young gay and bisexual men (YGBM) who were in the midst of their coming-out. Cross-sectional data regarding the first episode of anal intercourse were extracted from Outcomes, a longitudinal study on coming-out and sexual behavior of YGBM in the Netherlands. Overall, 45% of respondents reported unprotected anal intercourse (UAI) with their first same-sex partner. Rates of UAI did not significantly differ between meeting place (offline vs. online) and partner status (steady, regular or casual). PMID- 20300820 TI - Barriers to pharmacy-based syringe purchase among injection drug users in Tijuana, Mexico: a mixed methods study. AB - Injection drug users (IDUs) may be denied purchase of sterile syringes even where purchase without a prescription is legal. This study examined barriers to over the-counter (OTC) syringe purchase among IDUs in Tijuana, Mexico. A quantitative survey and subsequent focus groups were used to quantify barriers to purchase, identify their correlates and provide in-depth exploration of syringe purchase experiences. Of 627 IDUs, 81% purchased a syringe in the past 6 months and 16% were refused or overcharged. Factors independently associated with refusal/overcharging were homelessness, receptive syringe sharing, >5 uses per syringe, and number of lifetime abscesses. Few pharmacies sold syringes to IDUs, who adapted by limiting purchase attempts to pharmacies known to sell syringes consistently. Failed purchases occurred when drug withdrawal required purchase at unusual times or locations, often following release from jail. IDUs reported syringe sharing, syringe reuse, and searching through unsecured medical waste for syringes in response to failed purchase attempts. Interventions to expand OTC syringe sales to IDUs, particularly near detention facilities, will facilitate safer injection practices. PMID- 20300822 TI - Inside the black box: assessing and improving quality in youth programs. AB - Over the past decade, structured programming for children and youth during the non-school hours has expanded exponentially. A confluence of recent research studies and program evaluations backs the publicly perceived notion that after school programs can positively influence important developmental and learning outcomes. The rapid expansion of the field and the potential of programs to contribute to child and youth development have made defining what high quality programs look like and learning how to improve program quality key challenges facing the field. This paper describes what is known about the relation between youth program quality and youth developmental outcomes, summarizes different quality assessment tools being used in the field, and discusses how such tools are being used to drive systemic quality improvement efforts. PMID- 20300821 TI - Examining the potential of community-based after-school programs for Latino youth. AB - Results are presented from two pilot studies examining the potential influence of community-based after-school programs (ASPs) on regionally diverse Latino youth of varying ages. Study 1 examined relations between dimensions of ASP attendance and content, and ethnic identity development, and self-worth in urban Latino adolescents. In this study, higher ratings of the ASP's emphasis on ethnic socialization were associated with a more developed ethnic identity, while greater intensity of ASP participation and perceptions of ASP quality were associated with higher levels of self-worth. Study 2 examined relations between ASP participation and development of concentration and emotion regulation skills in rural Latino grade-school youth. In this study, youth who regularly attended the ASP demonstrated significantly better concentration and regulation skills than those who did not regularly attend, if they exhibited preexisting concentration and regulation problems. Findings illustrate how ASPs with varying strategies, activities, and assessment tools can be evaluated in the interest of designing future large-scale investigations into ASPs and Latino positive youth development. PMID- 20300823 TI - More than attendance: the importance of after-school program quality. AB - A central theme of the articles featured in this issue is the need to improve the quality of after-school programs. In this commentary, we discuss why student engagement, program characteristics and implementation, staff training, and citywide policy are key considerations in the effort to define and achieve high quality programs for youth. PMID- 20300824 TI - Dilemmas of practice: challenges to program quality encountered by youth program leaders. AB - To create and sustain high quality youth development programs it is important to understand the challenging situations and dilemmas that emerge in program leaders' daily work with youth. In this research the experiences of leaders in 12 programs were followed over a 2-9 month period, which led to the identification of 250 dilemma situations. Qualitative analyses identified 5 categories and 12 subcategories of dilemmas that reflected distinct types of considerations (e.g., youth's personalities, relationships with the community). The analyses also found that the experienced leaders in the study typically responded to these dilemmas in ways that were youth-centered and that balanced multiple considerations. It is argued that researchers need to go beyond identifying features of high quality programs, and more fully examine how effective leaders create and sustain high quality in response to the challenging situations of practice. PMID- 20300825 TI - A meta-analysis of after-school programs that seek to promote personal and social skills in children and adolescents. AB - A meta-analysis of after-school programs that seek to enhance the personal and social skills of children and adolescents indicated that, compared to controls, participants demonstrated significant increases in their self-perceptions and bonding to school, positive social behaviors, school grades and levels of academic achievement, and significant reductions in problem behaviors. The presence of four recommended practices associated with previously effective skill training (SAFE: sequenced, active, focused, and explicit) moderated several program outcomes. One important implication of current findings is that ASPs should contain components to foster the personal and social skills of youth because youth can benefit in multiple ways if these components are offered. The second implication is that further research is warranted on identifying program characteristics that can help us understand why some programs are more successful than others. PMID- 20300826 TI - Current evidence on the relationship between three polymorphisms in the FGFR2 gene and breast cancer risk: a meta-analysis. AB - In this article, inconsistency of the association of polymorphisms of fibroblast growth factor receptor 2 (FGFR2) with breast cancer is noted. Three commonly studied FGFR2 polymorphisms including rs1219648 (A > G), rs2420946 (C > T), and rs2981582 (C > T) were selected to explore their association with risk of development of breast cancer by meta-analysis of published case-control studies. The results showed that all these three polymorphisms were significantly associated with altered breast cancer risk in any model (co-dominant, dominant, or recessive model) and in stratification based on ethnicity and study design. In the subgroup analyses for postmenopausal women, significantly increased risks were found for rs1219648 and rs2420946 in any model. This meta-analysis suggests that FGFR2 is likely an important genetic marker contributing to susceptibility of breast cancer. We recommend that these single nucleotide polymorphisms to be included in future association studies and functional assays. PMID- 20300827 TI - Stimulation of retinoic acid-induced functional sodium iodide symporter (NIS) expression and cytotoxicity of 131I by carbamazepine in breast cancer cells. AB - The sodium iodide symporter (NIS) mediates the active iodide uptake in the thyroid gland as well as lactating breast tissue. Recently, we reported significant stimulation of all-trans retinoic acid (atRA)-induced NIS expression in the estrogen-receptor positive human breast cancer cell line MCF-7 by dexamethasone (Dex) in vitro and in vivo, which might offer the potential to image and treat breast cancer with radioiodine. In this study, based on its known interaction with the pregnane-X-receptor (PXR) forming a heterodimer with the retinoid-X-receptor (RXR), we examined the effect of carbamazepine (CBZ), a potent activator of PXR, on atRA-induced NIS expression and therapeutic efficacy of (131)I in MCF-7 cells. For this purpose, functional NIS expression in MCF-7 cells was examined by iodide uptake assay, quantitative real-time PCR as well as Western blot analysis, followed by investigation of (131)I cytotoxicity in vitro after incubation with CBZ (4, 25, 100 MUM) in the presence of atRA (1 MUM) with or without Dex (100 nM). Incubation with CBZ stimulated atRA-induced iodide accumulation up to twofold in a concentration-dependent manner, while atRA/Dex stimulated iodide uptake was further stimulated up to 1.5-fold by additional CBZ treatment based on significantly increased NIS mRNA and protein levels. This stimulatory effect of CBZ was shown to be dependent on the PI3K-Akt pathway without involvement of mTOR. In contrast, treatment with CBZ alone had no effect on functional NIS expression. Moreover, selective cytotoxicity of (131)I was significantly increased from approximately 20% in MCF-7 cells treated with atRA alone to 50% after treatment with CBZ in the presence of atRA, which was further enhanced to 90% after combined treatment with atRA/Dex/CBZ. In conclusion, CBZ represents another potent stimulator of atRA-induced functional NIS expression resulting in an enhanced selective killing effect of (131)I in MCF-7 breast cancer cells. PMID- 20300828 TI - Metformin inhibits aromatase expression in human breast adipose stromal cells via stimulation of AMP-activated protein kinase. AB - AMP-activated protein kinase (AMPK) is recognized as a master regulator of energy homeostasis. In concert with the AMPK-kinase LKB1, it has been shown to provide a molecular link between obesity and postmenopausal breast cancer via its actions to inhibit aromatase expression, hence estrogen production, within the breast. The anti-diabetic drug metformin is known to increase the activity of AMPK and was therefore hypothesized to inhibit aromatase expression in primary human breast adipose stromal cells. Results demonstrate that metformin significantly decreases the forskolin/phorbol ester (FSK/PMA)-induced expression of aromatase at concentrations of 10 and 50 muM. Consistent with the hypothesized actions of metformin to increase AMPK activity, treatment with 50 muM metformin results in a significant increase in phosphorylation of AMPK at Thr172. Interestingly, metformin also causes a significant increase in LKB1 protein expression and promoter activity, thereby providing for the first time an additional mechanism by which metformin activates AMPK. Furthermore, metformin inhibits the nuclear translocation of CRTC2, a CREB-coactivator known to increase aromatase expression which is also a direct downstream target of AMPK. Overall, these results suggest that metformin would reduce the local production of estrogens within the breast thereby providing a new key therapeutic tool that could be used in the neoadjuvant and adjuvant settings and conceivably also as a preventative measure in obese women. PMID- 20300829 TI - The PHSCN dendrimer as a more potent inhibitor of human breast cancer cell invasion, extravasation, and lung colony formation. AB - The alpha5beta1 integrin fibronectin receptor is an attractive therapeutic target in breast cancer because it plays key roles in invasion and metastasis. While its inactive form is widely expressed, activated alpha5beta1 occurs only on tumor cells and their associated vasculature. The PHSCN peptide has been shown to bind activated alpha5beta1 preferentially, thereby blocking invasion in vitro, and inhibiting growth, metastasis and tumor recurrence in preclinical models. Moreover in a recent Phase I clinical trial, systemic PHSCN monotherapy was well tolerated, and metastatic disease failed to progress for 4-14 months in 38% of patients receiving it. A significantly more potent PHSCN derivative, the PHSCN polylysine dendrimer (Ac-PHSCNGGK-MAP) has recently been developed. We report that it is 1280- to 6700-fold more potent than the PHSCN peptide at blocking alpha5beta1 mediated SUM-149 PT and MDA-MB-231 human breast cancer cell invasion of naturally occurring basement membranes in vitro. Chou-Talalay analysis of these data suggested that invasion inhibition by the PHSCN dendrimer was highly synergistic. We also report that, consistent with its enhanced invasion inhibitory potency, the PHSCN dendrimer is 700- to 1100-fold more effective than the PHSCN peptide at preventing SUM-149 PT and MDA-MB-231 extravasation in the lungs of athymic, nude mice. Our results also show that many extravasated SUM-149 PT and MDA-MB-231 cells go on to develop into metastatic colonies, and that pretreatment with the PHSCN dendrimer is more than 100-fold more effective at reducing lung colony formation. Since many patients newly diagnosed with breast cancer already have locally advanced or metastatic disease, the availability of a well-tolerated, nontoxic systemic therapy that can prevent metastatic progression by blocking invasion could be very beneficial. PMID- 20300830 TI - Accumulation and remobilization of metals in superficial sediments in Tianjin, China. AB - The concentrations of Cr, Ni, Cu, Zn, Cd, and Pb in superficial sediment samples collected from three representative sites (Yuqiao Reservoir, Haihe River, and Haihe River Estuary) in Tianjin, North China, were analyzed using various single extraction and sequential extraction procedures to determine their remobilization, extractability, and distribution patterns. Sediments from the Haihe River had higher metal concentrations and geo-accumulation indices, especially for Cd and Zn, than sediments from the other two sites, suggesting that the Haihe River has been heavily influenced by anthropogenic activities. In addition, over 31% and 28.2% of the total Cd in the Haihe River and the Yuqiao Reservoir, respectively, and 18.2% of the total Zn in the Haihe River were found to be associated with the exchangeable form, indicating the significant remobilization of Cd and Zn when compared with Cr and Ni. However, over 98% of the Ni and 78% of the Cr were most closely associated with the residue and oxidizable fractions, which resulted in their becoming environmentally immobile. Based on the Environmental Protection Agency method 3050B, Cd and Zn had the greatest extraction efficiency when a single extraction procedure using 0.5-mol L(-1) HCl, 0.43-mol L(-1) HAcO, and 0.05-mol L(-1) ethylene-diamine-tetra-acetic acid was conducted, with extraction yields of up to 72%, 68%, and 56% for Cd and 50%, 49%, and 29% for Zn, respectively, being obtained for the Haihe River sediments. This was followed by the yields of Cu and Pb and, finally, those of unpolluted metals such as Cr and Ni. HCl and acetic acid extraction provided equivalent information for predicting Cd and Zn mobility in the sediments studied and produced suitable results for quick screening. PMID- 20300831 TI - Study of heavy metal pollution in seawater of Kepez harbor of Canakkale (Turkey). AB - In this work, the heavy metals cadmium and lead in Kepez harbor were studied with regard to the determination of the environmental pollution levels. Seawater samples of the Dardanelles (Canakkale Strait) were collected from the nearest station to Kepez harbor in July 2007. Then, the concentrations of these metals were determined after simple pretreatment of samples by the proposed inductively coupled plasma-atomic emission spectrometry (ICP-AES) method. The analysis of a given sample is completed in about 15 min by the ICP-AES method, and the concentrations of Cd and Pb were found to be 73.80 mg L(-1) (relative standard deviation [RSD], 1.07%) and 9.39 mg L(-1) (RSD, 0.70%), respectively. The accuracy of the applied ICP technique was checked by recovery studies, and good recoveries were obtained. The pollution levels of Cd and Pb recorded in this study were compared with those in other studies to analyze the water sample in Kepez harbor. PMID- 20300832 TI - PAHs in soils and estimated air-soil exchange in the Pearl River Delta, South China. AB - In this study, 74 soil samples collected from the Pearl River Delta were analyzed for polycyclic aromatic hydrocarbons (PAHs). The PAH mixture in the soils is mainly of low molecular weight compounds, with naphthalene (21.4%) and phenanthrene (21.8%) being dominant. Soil PAH levels from the Pearl River Delta are relatively low (28-711 ng/g, averaged 192 ng/g) compared to those from urban soils in temperate regions. The mean concentration of SigmaPAHs generally decrease with increasing distance from the city center, with SigmaPAHs of paddy soils>crop soil>natural soil. PAHs in the air were measured during a year-round sampling campaign using semipermeable membrane devices, and the transfer of chemicals between the soil and air compartments were estimated. Soil-air fugacity quotient calculations showed a highly uncertain equilibrium position of PAHs, with net volatilization of naphthalene and fluorene, whereas net deposition of phenanthrene, fluoranthene, and pyrene, indicating a capacity for the air to supply the soil with more substances. PMID- 20300833 TI - Airborne pollen of ornamental tree species in the NW of Spain. AB - This study analyzed airborne pollen counts for the tree taxa most widely used for ornamental purposes in the northwestern Iberian Peninsula (Platanus, Cupressaceae, Olea, Myrtaceae, Cedrus, and Casuarina) at four sites (Vigo, Ourense, Santiago, and Lugo), using aerobiological data recorded over a long period (1993-2007). The abundance and the temporal and spatial distribution of these pollen types were analyzed, and the influence of weather-related factors on airborne pollen counts was assessed. Platanus (in Ourense) and Olea (in Vigo) were the taxa contributing most to pollen counts. In general terms, the results may be taken as indicators of potential risk for pollen-allergy sufferers and therefore used in planning future green areas. PMID- 20300834 TI - Stagnant surface water bodies (SSWBs) as an alternative water resource for the Chittagong metropolitan area of Bangladesh: physicochemical characterization in terms of water quality indices. AB - The concern over ensuing freshwater scarcity has forced the developing countries to delve for alternative water resources. In this study, we examined the potential of stagnant surface water bodies (SSWBs) as alternative freshwater resources in the densely populated Chittagong metropolitan area (CMPA) of Bangladesh--where there is an acute shortage of urban freshwater supply. Water samples were collected at 1-month intervals for a period of 1 year from 12 stations distributed over the whole metropolis. Samples were analyzed for pH, water temperature (WTemp), turbidity, electrical conductivity (EC), total dissolved solids, total solids, total hardness, dissolved oxygen (DO), chloride, orthophosphates, ammonia, total coliforms (TC), and trace metal (Cd, Cr, Cu, Pb, As, and Fe) concentrations. Based on these parameters, different types of water quality indices (WQIs) were deduced. WQIs showed most of CMPA-SSWBs as good or medium quality water bodies, while none were categorized as bad. Moreover, it was observed that the minimal water quality index (WQIm), computed using five parameters: WTemp, pH, DO, EC, and turbidity, gave a reliable estimate of water quality. The WQIm gave similar results in 72% of the cases compared with other WQIs that were based on larger set of parameters. Based on our finding, we suggest the wider use WQIm in developing countries for assessing health of SSWBs, as it will minimize the analytical cost to overcome the budget constraints involved in this kind of evaluations. It was observed that except turbidity and TC content, all other quality parameters fluctuated within the limit of the World Health Organization suggested standards for drinking water. From our findings, we concluded that if the turbidity and TC content of water from SSWBs in CMPA are taken care of, they will become good candidates as alternative water resources all round the year. PMID- 20300835 TI - Heavy metal concentrations in groundwaters and soils of Thane Region of Maharashtra, India. AB - Thane district is one of the most industrialized districts in Maharashtra. The heavy industrialization and the increasing urbanization are responsible for the rapidly increasing stress on the water and soil environment of the area. Therefore, an attempt has been made through comprehensive study on the groundwater contamination and soil contamination due to heavy metals in Thane region of Maharashtra. The area undertaken for the study was Thane and its suburbans Kalwa, Divajunction, Dombivali, Kalyan, and Ulhasnagar. Industrialization and urbanization lead to generation of large volumes of wastewater from domestic, commercial, industrial, and other sources, which discharged in to natural water bodies like river and creek in this region. Groundwater samples and soil samples were collected from residential, commercial, agriculture, and industrial areas. Groundwater samples were analyzed for various water quality parameters. The analytical data shows very high concentration of total dissolved solids, total hardness, total alkalinity, chemical oxygen demand, chloride etc. Groundwater and soil samples were analyzed for ten heavy metals by inductively coupled plasma (ICPE-9000) atomic emission spectroscopy. The analytical data reveal that, very high concentration level of arsenic, cadmium, mercury, and nickel throughout the industrial area. The random dumping of hazardous waste in the industrial area could be the main cause of the groundwater and soil contamination spreading by rainwater and wind. In the residential areas the local dumping is expected to be the main source for heavy metals. A comparison of the results of groundwater with WHO guidelines show that most of the groundwater sampling station are heavily contaminated with organic matter and heavy metals. Groundwater samples are heavily contaminated by arsenic, cadmium, mercury, and nickel. Similarly, the results of heavy metals in soil compared with Swedish soil guideline values for polluted soil show that soil samples collected from residential, commercial and industrial areas are heavily contaminated by arsenic, cadmium, mercury, and nickel. PMID- 20300836 TI - Analysis of the environmental impact on a stream: is only tannery to blame? AB - The contribution of wastewater from a tannery industry to the pollution of a stream was investigated. The main parameters studied were biochemical oxygen demand, chemical oxygen demand, chromium, dissolved oxygen, fecal and total coliforms, nitrogen, oils and greases, pH, phosphorous, sulfides, suspended solids, turbidity, and volatile solids. Three sampling points were located: (1) at the discharge point of tannery wastewater, (2) 50 m upstream, and (3) 80 m downstream of discharge point. Also was investigated the pollution at the stream source. PMID- 20300837 TI - Nitrate levels modulate denitrification activity in tropical mangrove sediments (Goa, India). AB - A study to examine the short-term effect of nitrate and organic carbon addition on denitrification activity was carried out on sediments from a mangrove ecosystem prone to anthropogenic activities (Divar, Goa, India). Laboratory microcosms were prepared using sediment sectioned at every 2-cm-depth interval from the surface to 10 cm. The incubations were subjected to varying nitrate amendments at concentrations ranging from 0, 5, 10, 20, 40 to 60 MUmol l(-1) (up to three times more than measured in field). Nitrous oxide production rates increased significantly (n=15; p<0.001) on addition of the nutrient at all depths investigated indicating that denitrification in mangrove sediments was NO[Formula: see text] limited. Incubations amended with organic carbon were prepared using glucose as a substrate with concentrations ranging from 0%, 0.1%, 0.3%, 0.5%, 0.75% to 1%. No significant increase in N2O production was observed on organic C addition. When both the substrates were in excess (1 mmol KNO3+1 mmol glucose), potential denitrification rates decreased with depth and were up to 38 times higher than the in situ denitrification activity varying from 81.26 to 304.09 MUmol N2O-N m(-2) h(-1). These results reveal that mangrove sediments could act as a sink for nitrate and microbially mediated denitrification could effectively reduce N load controlling any adverse environmental impact in the adjoining estuarine system. PMID- 20300838 TI - Water quality decline in coastal aquifers under anthropic pressure: the case of a suburban area of Dakar (Senegal). AB - In recent years, the unregulated increase of the population in coastal areas of developing countries has become source of concern for both water supply and quality control. In the region of Dakar (Senegal), approximately 80% of water resources come from groundwater reservoirs, which are increasingly affected by anthropogenic pressures. The identification of the main sources of pollution, and thus the aquifer vulnerability, is essential to provide a sound basis for the implementation of long-term geochemically based water management plans in this sub-Saharan area. With this aim, a hydrochemical and isotopic survey on 26 wells was performed in the so-called Peninsula of Cap-Vert. Results show that seawater intrusion represents the main process affecting groundwater chemical characteristics. Nitrates often exceed the World Health Organization drinking water limits: stable isotopes of dissolved nitrate (delta15N and delta18O) indicate urban sewage and fertilizers as a major source of contamination. Results depict a complex situation in which groundwater is affected by direct and indirect infiltration of effluents, mixing with seawater and freshening processes from below. Besides the relevance of the investigation at a regional level, it represents a basis for decision-making processes in an integrated water resources management and in the planning of similar monitoring strategies for other urban coastal regions. PMID- 20300839 TI - Water quality of a tributary of the Pearl River, the Beijiang, Southern China: implications from multivariate statistical analyses. AB - Water quality information of Beijiang River, a tributary of Pearl River in Guangdong, China, was analyzed to provide an overview of the hydrochemical functioning of a major agricultural/rural area and an industrial/urban area. Eighteen water quality parameters were surveyed at 13 sites from 2005 to 2006 on a monthly basis. A bivariate correlation analysis was carried out to evaluate the regional correlations of the water quality parameters, while the principal component analysis (PCA) technique was used to extract the most influential variables for regional variations of river water quality. Six principal components were extracted in PCA which explained more than 78% and 84% of the total variance for agricultural/rural and industrial/urban areas, respectively. Physicochemical factor, organic pollution, sewage pollution, geogenic factor, agricultural nonpoint source pollution, and accumulated pesticide usage were identified as potential pollution sources for agricultural/rural area, whereas industrial wastewaters pollution, mineral pollution, geogenic factor, urban sewage pollution, chemical industrial pollution, and water traffic pollution were the latent pollution sources for industrial/urban area. A multivariate linear regression of absolute principal component scores (MLR-APCS) technique was used to estimate contributions of all identified pollution sources to each water quality parameter. High coefficients of determination of the regression equations suggested that the MLR-APCS model was applicable for estimation of sources of most water quality parameters in the Beijiang River Basin. PMID- 20300840 TI - Scaffold-directed and traceless synthesis of tricyclic quinoxalinone imidazoles under microwave irradiation: for SCS-09 special issue-combinatorial approaches to drug discovery. AB - Traceless synthesis of 2-aminoimidazoquinoxalinones has been performed on soluble polymer support under open-vessel microwave dielectric heating. The reaction progression is monitored directly by the conventional proton NMR which indicated no release of the substrate from the support. Fmoc-deprotected amino acid polymer conjugates react with 1,5-difluoro-2,4-dinitro benzene to yield polymer bound dinitro fluoro amines, which are further substituted by various primary amines to yield PEG-immobilized dinitrodiamines. Simultaneous reduction of aromatic meta dinitro group leads to the traceless release of 2-quinoxalinones, followed by N hetero cyclization with various isothiocyanates in the presence of mercury(II)chloride to furnish 2-aminoimidazoquinolinone rings with three points of diversity at rapid pace. PMID- 20300842 TI - Vulnerable sites and changes in mucin in the rat small intestine after non steroidal anti-inflammatory drugs administration. AB - BACKGROUND AND AIMS: The location of mucosal damage and changes in mucin content in the rat small intestine following administration of non-steroidal anti inflammatory drugs (NSAIDs) have not been well elucidated. METHODS: After subcutaneous administration of loxoprofen sodium (10-40 mg/kg), the small intestinal mucosa of male Wistar rats was evaluated macroscopically, histologically, and immunohistochemically by measuring the total mucin content and immunoreactivity for anti-mucin monoclonal antibody, HCM31, 1, 3, 7, and 14 days later. Changes in the number of enterobacteria invading the mucosa around the lesions were also determined. RESULTS: Loxoprofen sodium induced erosions and ulcers along the mesenteric margin of the distal jejunum. Early (<=6 h) mucosal lesions were small and round, located between the branches of the mesenteric arteries. In the jejunum, there was a transient increase in the total mucin content, and HCM31-positive mucin in the mucosa around the ulcers increased significantly on days 3 and 7, but in the ileum there were no marked changes and few ulcers. Bacterial translocation following loxoprofen sodium administration significantly increased, according to the site of the intestinal lesions. CONCLUSIONS: Vascularly compromised sites along the jejunal mesenteric margin are vulnerable to NSAIDs-induced damage and show increased numbers of enterobacteria in the NSAIDs-treated mucosa. Increased sialomucin content in the mucus around the lesions may play an important role in the healing of NSAIDs-induced intestinal lesions. PMID- 20300841 TI - Esophageal adenocarcinoma: treatment modalities in the era of targeted therapy. AB - Esophageal adenocarcinoma is an aggressive malignancy with a poor outcome, and its incidence continues to rise at an alarming rate. Current treatment strategies combining chemotherapy, radiation, and surgery are plagued with high rates of recurrence and metastasis. Multiple molecular pathways including the epidermal growth factor receptor, vascular endothelial growth factor, v-erb-b2 erythroblastic leukemia viral oncogene homolog (ERBB2), and Aurora kinase pathways are activated in many esophageal adenocarcinomas. In many cases, these pathways have critical roles in tumor progression. Research on the mechanisms by which these pathways contribute to disease progression has resulted in numerous biologic agents and small molecules with the potential to improve outcome. The promise of targeted therapy and personalized medicine in improving the clinical outcome is now closer than it has ever been. PMID- 20300843 TI - Is BRAF mutation associated with interval colorectal cancers? AB - INTRODUCTION: Colon cancers diagnosed in the interval after a complete colonoscopy may occur due to limitations of colonoscopy or due to rapid tumor growth. The aim of this study was to compare the association of BRAF V600E mutation in interval versus non-interval colorectal cancers and to determine the relationship between BRAF mutation and 5-year survival. METHODS: We searched our institution's cancer registry for interval cancers, defined as colon cancers that developed within 5 years of a complete colonoscopy. These were frequency matched to patients with non-interval cancers. Archived cancer specimens were tested for BRAF V600E mutation and MSI. RESULTS: There were 63 interval and 131 non-interval cancers. BRAF mutation was present in 28% of interval cancers compared to 19% of non-interval cancers (P = 0.18). In a multivariable logistic regression model, proximal location (OR 1.85; 95% CI 1.01-3.8) and MSI (OR 2.7; 95% 1.1-6.8) were independently associated with interval cancers while BRAF mutation was not (OR 0.93; 95% CI 0.36-2.38). BRAF mutation portended a poor 5-year survival, particularly among microsatellite stable cancers. CONCLUSIONS: BRAF mutation is not associated with interval cancers but is a marker of poor prognosis, particularly in microsatellite stable cancers. PMID- 20300844 TI - Increased prevalence of reduced estimated glomerular filtration rate in chronic hepatitis C patients. AB - BACKGROUND: To investigate the prevalence and severity of reduced estimated glomerular filtration rate (eGFR) in patients with chronic hepatitis C (CHC). METHODS: Medical record review of 831 consecutive CHC patients seen in our clinic between July 2000 and August 2003; eGFR was estimated using the abbreviated Modification of Diet in Renal Disease (aMDRD) equation. The stage of kidney disease was determined based on eGFR expressed in milliliters per minute per 1.73 m(2): stage 1 (signs of kidney damage but normal or elevated (eGFR >or= 90), stage 2 (eGFR 60-89), stage 3 (30-59), stage 4 (eGFR 15-29), stage 5 (eGFR < 15 or dialysis-dependent). RESULTS: A total of 522 patients had available data with using the aMDRD equation, 51% had abnormal eGFR (stage 1, 4.6%; stage 2, 36.4%; stage 3 or 4, 6.1%; stage 5, 3.8%). Of 190 patients with stage 2 kidney disease, 189 patients (99.5%) had normal serum creatinine and only one patient (0.5%) had elevated creatinine concentrations (>1.4 mg/dl). Of the 32 patients with stage 3 or 4 disease, 20 (62.5%) had a normal serum creatinine concentration. Of 349 patients without diseases known to cause renal insufficiency, 38% had stage 2-4 renal disease. In a subset of these patients, 95/522 (18%) the measured creatinine clearance showed good correlation with their aMDRD (R = 0.47, (p < 0.0001). CONCLUSIONS: In CHC patients, a normal serum creatinine concentration does not assure normal kidney function. Estimation of eGFR with the aMDRD equation is a more accurate method of identifying patients with chronic kidney disease and reduced eGFR. Therefore, CHC patients should be screened more rigorously for chronic kidney disease because of the high prevalence of reduced eGFR. Lastly, in all CHC patients, the aMDRD eGFR should be used in each encounter with these patients when assessing their renal function irrespective of their serum creatinine. PMID- 20300845 TI - Abnormal small-intestinal endocrine cells in patients with irritable bowel syndrome. AB - BACKGROUND: General disturbances in gastrointestinal motility have been reported in patients with irritable bowel syndrome (IBS). The gastrointestinal tract hormones play an important role in regulating gastrointestinal motility. AIMS: To investigate a possible abnormality in the small intestinal endocrine cells of IBS patients. METHODS: Included in the study were 41 patients with irritable bowel syndrome according to Rome Criteria III and 42 healthy controls. Duodenal biopsies were obtained from both patients and controls during gastroscopy. The biopsies were immunostained by avidin-biotin-complex method for secretin, CCK, GIP, somatostatin, and serotonin cells. The cell densities were quantified by computerized image analysis. RESULTS: The density of secretin- and CCK immunoreactive cells in patients with IBS was significantly reduced. The reduction in secretin and CCK cells occurred only in IBS-diarrhea patients, but not in IBS-constipation subtype. Both GIP and somatostatin cell densities were reduced in the duodenum of IBS patients. There was no statistical difference between the subtypes of IBS patients, regarding secretin, CCK, GIP, or somatostatin cell densities. Serotonin cell density was not affected in patients with IBS. CONCLUSIONS: The low densities of secretin and CCK cells in IBS diarrhea patients may cause a functional pancreatic insufficiency as well as inadequate gall emptying, as these hormones stimulate pancreatic bicarbonate and enzyme secretion and CCK stimulates as well gall bladder contraction. Low densities of secretin, GIP, and somatostatin cells in IBS patients might result in a high secretion of gastric acid, as secretin, GIP, and somatostatin inhibit gastric acid secretion. PMID- 20300846 TI - Electromagnetically controlled biological assembly of aligned bacterial cellulose nanofibers. AB - We have developed a new biofabrication process in which the precise control of bacterial motion is used to fabricate customizable networks of cellulose nanofibrils. This article describes how the motion of Acetobacter xylinum can be controlled by electric fields while the bacteria simultaneously produce nanocellulose, resulting in networks with aligned fibers. Since the electrolysis of water due to the application of electric fields produces the oxygen in the culture media far from the liquid-air boundary, aerobic cellulose production in 3D structures is readily achievable. Five separate sets of experiments were conducted to demonstrate the assembly of nanocellulose by A. xylinum in the presence of electric fields in micro- and macro-environments. This study demonstrates a new concept of bottom up material synthesis by the control of a biological assembly process. PMID- 20300847 TI - The effect of stent porosity and strut shape on saccular aneurysm and its numerical analysis with lattice Boltzmann method. AB - The analysis of a flow pattern in cerebral aneurysms and the effect of stent strut shapes are presented in this article. The treatment of cerebral aneurisms with a porous stent has recently been proposed as a minimally invasive way to prevent rupture and favor coagulation mechanism inside the aneurism. The efficiency of stent is related to several parameters, including porosity and stent strut shapes. The goal of this article is to study the effect of the stent strut shape and porosity on the hemodynamic properties of the flow inside an aneurysm using a numerical analysis. In this study, we use the concept of flow reduction to characterize the stent efficiency. Also, we use the lattice Boltzmann method (LBM) of a non-Newtonian blood flow. To resolve the characteristics of a highly complex flow, we use an extrapolation method for the wall and stent boundary. To ease the code development and facilitate the incorporation of new physics, a scientific programming strategy based on object oriented concepts is developed. Reduced velocity, smaller average vorticity magnitude, smaller average shear rate, and increased viscosity are observed when the proposed stent shapes and porosities are used. The rectangular stent is observed to be optimal and to decrease the magnitude of the velocity by 89.25% in the 2D model and 53.92% in the 3D model in the aneurysm sac. Our results show the role of the porosity and stent strut shape and help us to understand the characteristics of stent strut design. PMID- 20300848 TI - Peptide interfacial biomaterials improve endothelial cell adhesion and spreading on synthetic polyglycolic acid materials. AB - Resorbable scaffolds such as polyglycolic acid (PGA) are employed in a number of clinical and tissue engineering applications owing to their desirable property of allowing remodeling to form native tissue over time. However, native PGA does not promote endothelial cell adhesion. Here we describe a novel treatment with hetero bifunctional peptide linkers, termed "interfacial biomaterials" (IFBMs), which are used to alter the surface of PGA to provide appropriate biological cues. IFBMs couple an affinity peptide for the material with a biologically active peptide that promotes desired cellular responses. One such PGA affinity peptide was coupled to the integrin binding domain, Arg-Gly-Asp (RGD), to build a chemically synthesized bimodular 27 amino acid peptide that mediated interactions between PGA and integrin receptors on endothelial cells. Quartz crystal microbalance with dissipation monitoring (QCMD) was used to determine the association constant (K (A) 1 x 10(7) M(-1)) and surface thickness (~3.5 nm). Cell binding studies indicated that IFBM efficiently mediated adhesion, spreading, and cytoskeletal organization of endothelial cells on PGA in an integrin-dependent manner. We show that the IFBM peptide promotes a 200% increase in endothelial cell binding to PGA as well as 70-120% increase in cell spreading from 30 to 60 minutes after plating. PMID- 20300849 TI - Direct electrical stimulation using a battery-operated device for induction and modulation of colonic contractions in pigs. AB - Direct electrical stimulation of the colon offers a promising approach for the induction of propulsive colonic contractions by using an implantable device. The objective of this study was to assess the feasibility to induce colonic contractions using a commercially available battery-operated stimulator (maximum pulse width of 1 ms and maximum amplitude of 10 V). Three pairs of pacing electrodes were inserted into the cecal seromuscular layer of anesthetized pigs. During a first set of in vivo experiments conducted on six animals, a pacing protocol leading to cecum contractions was determined: stimulation bursts with 1 ms pulse width, 10 V amplitude (7-15 mA), 120 Hz frequency, and 30-s burst duration, repeated every 2-5 min. In a second testing phase, an evaluation of the pacing protocol was performed in four animals (120 stimulation bursts in total). By using the battery-operated stimulator, contractions of the cecum and movement of contents could be induced in 92% of all stimulations. A cecal shortening of about 30% and an average intraluminal pressure increase of 10.0 +/- 6.0 mmHg were observed. PMID- 20300850 TI - Computational tools for quantitative breast morphometry based on 3D scans. AB - Quantitative analysis of breast morphometry is critical to breast plastic surgery. Recently, three-dimensional (3D) photography has emerged as a strong new alternative for breast morphometry analysis in comparison to other existing techniques. 3D photography enables the capture of the entire breast surface topology virtually in a single snapshot and without any direct contact with the patient, thus causing minimal discomfort. In this paper, we present a set of computational tools for the quantitative analysis of two key morphological properties of the breast that are of interest to breast plastic surgery based on 3D scans, namely breast shape and volume. The breast shape is modeled using a compact geometric model capable of capturing the global shape of the breast with very few parameters. Specifically, the shape model is deduced by applying a set of five global deformations to a geometric primitive. These deformations, defined using very intuitive parameters, closely model the key shape variables that surgeons inherently use to describe the overall shape of the breast. Patient specific parameters of the breast shape model are automatically recovered by fitting a generic breast shape model to the 3D scan of the patient's breast using a physics-based deformable model framework. The mean error of fit between the automatically fitted shape model and the actual breast surface for 12 subjects varied between 0.9 and 2.6 mm. These results are very encouraging considering the fact that only 17 parameters are used to determine the shape of the breast. The breast volume is estimated automatically by first localizing the breast on a 3D scan of the patient's torso and then computing the volume enclosed between an interpolated breast-less torso surface and the actual breast. The volume estimated by the proposed method was found to be within the intra-operator variability among five segmentation trials performed manually by an expert on 3D torso scans of three subjects. PMID- 20300851 TI - Mapping the spatiotemporal dynamics of calcium signaling in cellular neural networks using optical flow. AB - An optical flow gradient algorithm was applied to spontaneously forming networks of neurons and glia in culture imaged by fluorescence optical microscopy in order to map functional calcium signaling with single pixel resolution. Optical flow estimates the direction and speed of motion of objects in an image between subsequent frames in a recorded digital sequence of images (i.e., a movie). Computed vector field outputs by the algorithm were able to track the spatiotemporal dynamics of calcium signaling patterns. We begin by briefly reviewing the mathematics of the optical flow algorithm, and then describe how to solve for the displacement vectors and how to measure their reliability. We then compare computed flow vectors with manually estimated vectors for the progression of a calcium signal recorded from representative astrocyte cultures. Finally, we applied the algorithm to preparations of primary astrocytes and hippocampal neurons and to the rMC-1 Muller glial cell line in order to illustrate the capability of the algorithm for capturing different types of spatiotemporal calcium activity. We discuss the imaging requirements, parameter selection and threshold selection for reliable measurements, and offer perspectives on uses of the vector data. PMID- 20300852 TI - Large neutral amino acids in daily practice. AB - At the Kennedy Centre for Phenylketonuria, Denmark, large neutral amino acids (LNAAs) are being used to treat adult and adolescent patients who are nonadherent to dietary treatment for phenylketonuria (PKU). At the start of treatment, a patient must undergo dietary analysis and regular blood sampling to measure plasma amino acid (AA) concentrations. The aim of this analysis and treatment is that the patient receives 25-30% of the daily protein requirement from LNAA supplementation and the remaining 70-75% from natural, low-phenylalanine proteins (although some patients have difficulties in maintaining this level of protein intake). Patients are therefore able to follow a more "normal" diet than those adhering to a PKU diet with AA supplementation (in which only 20% of the daily protein requirement is provided from the diet and 80% from AA supplementation). LNAAs have also been used to treat older patients with untreated/late-diagnosed PKU who show profound intellectual, psychological, and behavioral impairments. Treatment with LNAAs has been shown to improve measures of concentration and awareness of external stimuli in some of these patients and thus enhance their socialization, emotionality, frustration tolerance, and mood. PMID- 20300854 TI - Rapid detection of pathogens using antibody-coated microbeads with bioluminescence in microfluidic chips. AB - Detection of pathogens was demonstrated in a polydimethylsiloxane (PDMS)/glass microfluidic chip with which microbead-based immunoseparation platform and the bioluminescence technology were integrated. Escherichia coli (E. coli) O157:H7 was used as the model bacteria. The microchamber in microfluidic chip was filled with glass beads coated with antibodies which could capture specific organism, and the capture efficiency of the chip for the bacteria was about 91.75% approximately 95.62%. Then the concentration of bacteria was determined by detecting adenosine triphosphate (ATP) employing bioluminescence reaction of firefly luciferin-lucifera-ATP on chip. The method allowed reliable detection of E. coli O157:H7 concentrations from 3.2 x 10(1) cfu/microL to 3.2 x 10(5) cfu/microL within 20 min. This research demonstrated excellent reproducibility, stability, and specificity, and could accurately detect the pathogenic bacteria in food samples. The microfluidic chip and the equipments used in this method are easy to miniaturize, thus the method has great potential to be developed to a portable device for rapid detection of pathogens. PMID- 20300853 TI - Fatal cerebral edema associated with serine deficiency in CSF. AB - Two young girls without a notable medical history except for asthma presented with an acute toxic encephalopathy with very low serine concentrations both in plasma and cerebrospinal fluid (CSF) comparable to patients with 3 phosphoglycerate dehydrogenase (3-PGDH) deficiency. Clinical symptoms and enzyme measurement (in one patient) excluded 3-PGDH deficiency. Deficiencies in other serine biosynthesis enzymes were highly unlikely on clinical grounds. On basis of the fasting state, ketone bodies and lactate in plasma, urine and CSF, we speculate that reduced serine levels were due to its use as gluconeogenic substrate, conversion to pyruvate by brain serine racemase or decreased L-serine production because of a lack of glucose. These are the first strikingly similar cases of patients with a clear secondary serine deficiency associated with a toxic encephalopathy. PMID- 20300855 TI - Mitochondria-targeting photosensitizer-encapsulated amorphous nanocage as a bimodal reagent for drug delivery and biodiagnose in vitro. AB - The use of ceramic nano-carriers containing anti-cancer drugs for targeted delivery that span both fundamental and applied research has attracted the interest of the scientific community. In this paper, a hydrophobic photodynamic therapy drug, hypocrellin A (HA), was successfully encapsulated in water-soluble amorphous silica nanocage (HANC) by an improved sol-gel method. These nanocages are of ultrasmall size, highly monodispersed, stable in aqueous suspension, and retain the optical properties of HA. Moreover, these nanocages can be effectively delivered, subsequently taken up by cancer cells and finally targeted to mitochondria. In addition, incubation time dependent photodynamic efficacy difference between HANC and HA was investigated for the first time. Especially, the nanocages, owning extremely high stable fluorescence comparing with free HA, also have potentials as efficient probes for optical biodiagnose in vitro. All these properties of HANC could possibly make it especially promising to be used as a bimodal reagent for photodynamic therapy and biodiagnose. PMID- 20300856 TI - Compressed collagen gel as the scaffold for skin engineering. AB - Collagen gel scaffolds can potentially be utilized as cell seeded systems for skin tissue engineering. However, its dramatic contraction after being mixed with cells and its mechanical weakness are the drawbacks for its application to skin engineering. In this study, a compressed collagen gel scaffold was fabricated through the rapid expulsion of liquid from reconstituted gels by the application of 'plastic compression'(PC) technique. Both compressed and uncompressed gels were characterized with their gel contraction rate, morphology, the viability of seeded cells, their mechanical properties and the feasibility as a scaffold for constructing tissue-engineered skin. The results showed that the compression could significantly reduce the contraction of the collagen gel and improve its mechanical property. In addition, seeded dermal fibroblasts survived well in the compressed gel and seeded epidermal cells gradually developed into a stratified epidermal layer, and thus formed tissue engineered skin. This study reveals the potential of using compressed collagen gel as a scaffold for skin engineering. PMID- 20300857 TI - A computational and experimental study inside microfluidic systems: the role of shear stress and flow recirculation in cell docking. AB - In this paper, microfluidic devices containing microwells that enabled cell docking were investigated. We theoretically assessed the effect of geometry on recirculation areas and wall shear stress patterns within microwells and studied the relationship between the computational predictions and experimental cell docking. We used microchannels with 150 microm diameter microwells that had either 20 or 80 microm thickness. Flow within 80 microm deep microwells was subject to extensive recirculation areas and low shear stresses (<0.5 mPa) near the well base; whilst these were only presented within a 10 microm peripheral ring in 20 microm thick microwells. We also experimentally demonstrated that cell docking was significantly higher (p < 0.01) in 80 microm thick microwells as compared to 20 microm thick microwells. Finally, a computational tool which correlated physical and geometrical parameters of microwells with their fluid dynamic environment was developed and was also experimentally confirmed. PMID- 20300858 TI - Microfluidic perifusion and imaging device for multi-parametric islet function assessment. AB - A microfluidic islet perifusion device was developed for the assessment of dynamic insulin secretion of multiple pancreatic islets and simultaneous fluorescence imaging of calcium influx and mitochondrial potential changes. The fanned out design of the second generation device optimized the efficient mixing and uniform distribution of rapid alternating solutions in the perifusion chamber and allowed for the generation of reproducible glucose gradients. Simultaneous imaging of calcium influx and mitochondrial potential changes in response to glucose stimulation showed high signal-noise ratio and spatial-temporal resolution. These results suggest that this system can be used for detailed study of the endocrine function of pancreatic islets with simultaneous imaging of intracellular ion fluxes and mitochondrial membrane potential changes. This tool can be used for quality assessment of islets preparation before transplantation and for in vitro studies of islet function. PMID- 20300859 TI - Serum testosterone in females exposed to natural sour gas with respect to polymorphisms of XRCC1, GSTM1, and GSTT1. AB - The present study was done to determine the modulation effect(s) of polymorphisms of XRCC1, GSTM1, and GSTT1 on concentration of serum testosterone in females exposed to natural sour gas. Also we examine whether chronic exposure to natural gas containing sulfur compounds act as natural selection force on XRCC1 polymorphisms. The present study was performed on 68 healthy unrelated female students living in polluted areas of MIS. Also for investigating the effect of natural selection on XRCC1 polymorphism, a study was performed on two groups of healthy individuals of MIS citizens. The first and second groups including 94 (age range 30-85 years) and 187 individuals (age range 5-20 years), respectively. First and second groups were born and were not born in contaminated areas of the MIS, respectively. There was no significant difference between genotypes of XRCC1 for concentration of serum testosterone. Although GSTT1-null genotype had higher level of serum testosterone in comparison with the present genotype (t=2.392, df=66, P=0.023), a borderline difference between genotypes of GSTM1 for serum testosterone was observed (t=1.928, df=66, P=0.058). Analysis of variance revealed significant difference between combination genotypes of GSTM1 and GSTT1 for serum testosterone (F=4.167; df=3, 64; P=0.009). The Duncan post hoc test indicated that the combination genotype of "present GSTM1/null GSTT1" had significant higher level of testosterone. There is no evidence that XRCC1 polymorphisms have advantage/disadvantage when population exposed to natural sour gas. The polymorphisms of GSTM1 and GSTT1 modulate serum testosterone concentration in young females exposed to natural sour gas. PMID- 20300860 TI - Identification of candidate genes associated with CBB resistance in common bean HR45 (Phaseolus vulgaris L.) using cDNA-AFLP. AB - Common bacterial blight (CBB), incited by Xanthomonas axonopodis pv. phaseoli (Xap), is a serious seed-borne disease of common bean (Phaseolus vulgaris L.) in both temperate and tropical production zones. The line HR45 is highly resistant to Xap infection on leaves and pods in both field and greenhouse. To understand the molecular mechanisms underlying CBB resistance in HR45, cDNA-amplified fragment length polymorphism (AFLP) technique was used to identify the genes that are differentially expressed in the leaves of HR45 at different time-periods after inoculation. Selective amplifications with 34 primer combinations allowed the visualization of 2,448 transcript-derived fragments (TDFs) in infected leaves, and 259 (10.6%) of them were differentially expressed TDFs (DE-TDFs). Seventy-seven of the DE-TDFs were cloned and sequenced. Thirty-nine of the 77 (50.6%) DE-TDFs representing bean transcripts were not previously reported in any EST database. The expression patterns of 10 representative DE-TDFs were further confirmed by real-time RT-PCR. BLAST analysis suggested that 40% (31 of 77) of the DE-TDFs were homologous to the genes related to metabolism, photosynthesis, and cellular transport, whereas 28% (22 of 77) of the DE-TDFs showed homology to the genes involved in defence response, response to stimulus, enzyme regulation, and transcription regulation. Thus, the 22 pathogenesis-related DE-TDFs were selected as potential functional candidate genes (FCGs) in association with CBB resistance. Meanwhile, six of the DE-TDFs (1FCG and five other DE-TDFs) were in silico mapped to the distal region of the bean linkage group B6 (the genomic location containing the major CBB resistance QTL in HR45) and, therefore, were considered as positional candidate genes (PCGs). This study represents a first step towards the discovery of bean genes expressed upon Xap infection. This information will be useful for elucidating the molecular basis of the resistance response process and identifying the genes that underlie the CBB-resistance. PMID- 20300861 TI - Loss of heterozygosity of the tumor suppressor gene Tg737 in the side population cells of hepatocellular carcinomas is associated with poor prognosis. AB - Analysis of loss of heterozygosity (LOH) is a useful method for finding genetic alterations in tumor and precancerous lesion tissues. In this study, we analyzed LOH of the tumor suppressor gene Tg737 in side population cells of human hepatocellular carcinomas. Side population cells were sorted and identification by flow cytometry from suspensions of hepatocarcinoma or normal liver cells generated from 95 hepatocellular carcinoma and normal tissues, respectively. DNA was extracted from the two groups of side population cells and peripheral blood specimens. Five microsatellite markers on the Tg737 gene were used to analyze the frequency of loss of heterozygosity in the side population cells of the hepatocellular carcinoma. Twenty-four (25.30%) tumor samples had a large deletion in more than three microsatellite markers. The highest frequency of loss of heterozygosity was observed with the G64212 marker (78.75%) and the SHGC-57879 marker (75.95%). Statistical analysis of the correlation between loss of heterozygosity of Tg737 and clinicopathological features indicated a strong correlation between the two markers associated with the highest frequency of loss of heterozygosity and survival. The results indicate that loss of heterozygosity of the tumor suppressor gene Tg737 may play an important role in the carcinogenetic mechanism of liver cancer stem cells. In addition, the independent association between loss of heterozygosity at the SHGC-57879 and G64212 markers and worsened short-term survival in patients could be used as a novel prognostic predictor. Further studies of side population cells may contribute to the establishment of novel therapeutic strategies for hepatocellular carcinoma. PMID- 20300862 TI - Polymorphisms of BMPR-IB gene and their relationship with litter size in goats. AB - The bone morphogenetic protein receptor IB (BMPR-IB) gene was studied as a candidate gene for the prolificacy of goats. According to mRNA sequence of ovine BMPR-IB gene, ten pairs of primers were designed to detect single nucleotide polymorphisms (SNPs) of exon 1, exon 2, exon 6 to exon 10 and 3' untranslated region (UTR) of the BMPR-IB gene in both high prolificacy breed (Jining Grey goat) and low prolificacy breeds (Wendeng Dairy and Inner Mongolia Cashmere goats) by polymerase chain reaction (PCR)-single strand conformation polymorphism (SSCP) method. Only the products amplified by primers P8 and P10 of the 3'UTR displayed polymorphisms. For primer P8, three genotypes (AA, AB and BB) were detected in Jining Grey and Wendeng Dairy goats, two genotypes (AA and AB) were in Inner Mongolia Cashmere goats. Sequencing revealed one mutation (71C->T) of the BMPR-IB gene in genotype BB compared with AA. The differences of least squares mean (LSM) for litter size between genotypes AA, AB and BB were non significant (P > 0.05) in Jining Grey goats. For primer P10, three genotypes (CC, CD and DD) were detected in Jining Grey and Wendeng Dairy goats and one genotype (CC) in Inner Mongolia Cashmere goats. Sequencing revealed one mutation (130T->C) of the BMPR-IB gene in genotype DD compared with CC. The differences of LSM for litter size between genotypes CC, CD and DD were non-significant (P > 0.05) in Jining Grey goats. These results preliminarily showed that the detected loci of the BMPR-IB gene had no significant effect on prolificacy of Jining Grey goats. PMID- 20300863 TI - Interleukin-8-251A/T polymorphism and Helicobacter pylori infection influence risk for the development of gastric cardiac adenocarcinoma in a high-incidence area of China. AB - Polymorphisms in cytokine genes may contribute to increased susceptibility to different cancers. The aim of this paper is to investigate the association of IL 8-251A/T polymorphism and Helicobacter pylori (H. pylori) infection with the risk of developing gastric cardiac adenocarcinoma (GCA) in the south of Taihang Mountain, a high-incidence area of esophageal cancer in China. The IL-8-251 A/T polymorphism was genotyped in 519 cases of GCA and 504 healthy controls. The H. pylori infection in GCA patients and controls was detected by rapid urease test (RUT), histopathology or (14)C-urea breath test ((14)C-UBT). The results showed that family history of upper gastrointestinal cancer (UGIC) and H. pylori infection significantly increased the risk of developing GCA. The overall genotype and allelotype distributions of IL-8 promoter SNPs in GCA patients were significantly different from those in healthy controls. Compared with TT genotype, AA genotype significantly elevated the risk of developing GCA. The stratification analysis revealed that, compared with the TT genotype, the AA genotype significantly elevated the risk of developing GCA in both positive family history of UGIC and H. pylori infection subgroups. This study provides evidence to support a relationship of increased susceptibility to GCA in individuals of the south Taihang Mountain region with IL-8 251 AA genotype, especially for those individuals who have family history of UGIC or H. pylori infection. PMID- 20300864 TI - Investigation of porcine FABP3 and LEPR gene polymorphisms and mRNA expression for variation in intramuscular fat content. AB - Porcine chromosome 6 (SSC6) has been reported to have QTL affecting intramuscular fat content (IMF) in multiple populations. The objective of this study was to investigate the effect of FABP3 and LEPR genetic variations as well as their mRNA expression on the IMF trait in a three-generation of Korean native pig and Yorkshire crossed animals. Several polymorphisms of the FABP3 (HinfI, HaeIII and HinfI*) were significantly associated with moisture, tenderness and flavor score (P < 0.05), and were used to construct haplotypes: haplotype 1 (-TCT-) increased the marbling and intramuscular fat content, however, haplotype 2 (-CCT-) decreased tenderness. The LEPR AvaII polymorphism showed significant association with moisture, intramuscular fat, cholesterol and flavor score (P < 0.05). The linkage analyses with six microsatellites mapped FABP3 gene in the interval between the markers Sw1129 and S0228 (Sw1129--11.7 cM--FABP3-9.1 cM--S0228), and the LEPR gene between the markers S0121 and Sw322 (S0121--7.5 cM--LEPR--28.5 cM- Sw322). QTL mapping suggested a significant QTL affecting Moisture (83 cM) and IMF (84 cM) located close to marker S0228. The gene expression results showed that in the loin muscle, both of the FABP3 and LEPR genes showed significantly higher expression in pigs with higher IMF%, however, in the backfat, only FABP3 showed differential expression between these two groups of pigs (significantly higher expression in pigs with lower IMF%) (P < 0.05). In the liver, both of these two genes did not show any difference between the high and low IMF% groups. PMID- 20300865 TI - Characterization of two cotton (Gossypium hirsutum L) invertase genes. AB - Two cotton vacuolar-invertase genes were identified and sequenced. Both genes had seven exons, including an unusually small second exon typical of acid invertases. These genes encode peptides with many features shared by acid invertases from other species including, leader sequences that probably target the peptide to the vacuole, active site motifs and substrate binding motifs. Expression analyses indicated that one of the genes was expressed in roots during the starch filling stage of development. However, expression of the same gene fluctuated during the starch utilization stage of development. Therefore this gene was unlikely to play a role in determining sink strength of this tissue. Both genes were expressed in elongating fibers where they were likely to play a role in cell expansion. The invertase gene uniquely expressed in fiber had a simple sequence repeat (SSR) in the third intron that was polymorphic among various cotton species. An EST was identified with an expansion of the SSR that included the third intron indicating this SSR is associated with a splice variant. The polymorphic SSR may be useful in investigating the function of this gene in fiber development. PMID- 20300866 TI - Quality-of-life measures in Taiwanese adults with symptomatic gallstone disease. AB - PURPOSE: The objective of this study was to investigate the association of quality-of-life status with baseline laboratory findings among Taiwanese adults having symptomatic gallstone disease. METHODS: A prospective quality-of-life survey was administered at a tertiary referral medical center among 102 consecutive adults with symptomatic gallstone disease. Patients underwent regular laboratory testing at admission and were evaluated using the 36-Item Short-Form Health Survey (SF-36) and the Gastrointestinal Quality of Life Index (GIQLI). Correlation and regression models were used to investigate quality-of-life predictors. RESULTS: Compared with the general Taiwanese adult population, patients having symptomatic gallstone disease had significantly poorer performance on all eight SF-36 subscales (P < 0.001). Total GIQLI showed moderate to strong correlation with all eight SF-36 subscale scores (gamma = 0.29 ~ 0.62, P < 0.05). In multivariate analysis, serum levels of direct bilirubin (beta = 32.6, P = 0.001) and alkaline phosphatase (beta = -13.6, P = 0.032) were predictive of worse total GIQLI (adjusted R (2) = 0.183). CONCLUSIONS: Symptomatic gallstone disease may considerably affect patient quality of life in terms of general health status and gastrointestinal-specific measures. Before gallstone surgery, serum levels of direct bilirubin and alkaline phosphatase significantly correlated with quality-of-life measures and can be used to evaluate patient well-being at admission. PMID- 20300867 TI - Novel one-stop multidisciplinary follow-up clinic significantly improves cancer risk management in BRCA1/2 carriers. AB - The purpose of this study is to measure the impact of a multidisciplinary one stop follow-up clinic (MDOSC) on breast and ovarian surveillance, risk reducing surgery and enrolment in clinical trials in BRCA1/2 carriers. All BRCA1/2 carriers in our region were invited and chose which specialists to see in our MDOSC offering best practice using clinical protocols based on national guidelines and published data. Uptake was evaluated over 24 months recording numbers of individuals undergoing breast and ovarian surveillance, risk reducing surgery, newly diagnosed cancers, their method of detection and participation in clinical trials. 172 (60%) of invited BRCA1/2 carriers chose to attend the MDOSC. Breast surveillance was initiated in 88% and screening frequency altered in 14% of women to comply with national guidelines. Risk reducing salpingo-oophorectomy was chosen by 47% of women and an additional 39% were considering it. The rate of failure to remove fallopian tubes fell from 15 to 3% of procedures (P < 0.01) and peritoneal washings and serial sectioning of tubes and ovaries rose from 25% and 14% before, to 67% (P < 0.001) and 63% (P < 0.001) procedures, respectively, after initiation of our MDOSC. 24% of women considered and 18% decided to undergo risk reducing mastectomy during the follow-up period. Participation in clinical trials increased significantly from 51 to 229 enrolments (P < 0.001). Our novel MDOSC designed to devise an individually tailored cancer risk management strategy had a high uptake amongst our BRCA1/2 carriers. Attendance resulted in improved breast and ovarian cancer risk management. PMID- 20300868 TI - Elevated blood lead levels and cytogenetic markers in buccal epithelial cells of painters in India: genotoxicity in painters exposed to lead containing paints. AB - BACKGROUND, AIM, AND SCOPE: Lead, a major contaminant, is highly used in paint manufacturing due to its anticorrosive properties. Recent reports indicated high lead content among Indian paints used for commercial purposes. Painters are continuously exposed to these lead containing paints during painting of both commercial as well as residential buildings. Lead is well-known for its genotoxicty in occupational workers; however, in Indian painters the genotoxic effects of lead have not been reported to date. Therefore we aimed to study the genotoxic end points in painters due to their long-term exposure to these high lead-containing Indian paints. MATERIALS AND METHODS: Study group selection was made after a questionnaire administration, which included questions about lifestyle and medical history to exclude exposure to the other potential sources of genotoxics. Blood and buccal cell samples were obtained from 30 male painters and from a similar number of age-matched controls of same location with no occupational exposure to lead. Blood lead levels (Pb-B) were measured in painters and controls. Micronucleus (MN) frequencies and nuclear changes, i.e., karyorrhexis, karyolysis, broken egg, and binucleated, were investigated in buccal epithelial cells. RESULTS: Painters had significantly (P < 0.01) greater lead levels in blood than the control group. MN frequencies and nuclear changes in buccal epithelial cells were also significantly (P < 0.01) elevated in painters as compared with control subjects. Regression analysis also revealed significant (P < 0.01) association of Pb-B with all the genotoxic endpoints in painters. Cytogenetic damage was significantly associated with Pb-B as no other co-founding factors (smoking, alcohols) showed significant difference between both groups. DISCUSSION: Lead is widely used in paints which may serve as potential source of exposure among painters due to their long-term engagement with paints. Our results clearly demonstrated genotoxicity among the exposed population as evident from increase micronucleus frequencies, frequent nuclear changes, and apoptosis. Many studies had previously related nuclear change events in buccal epithelial cells with the progression of different carcinomas. Furthermore in-depth investigations with larger sample size are needed to provide evidence to this effect. CONCLUSIONS: Here, we report cytogenetic toxicity to the exposed population by the high lead containing paints from India for the first time. Frequent, high and unregulated use of lead in paints may cause genetic mutation and may accelerate cytogenetic damage which may further lead to different carcinomas in painters. These findings need to be considered and necessary steps should be taken to protect the occupational workers engaged with these high lead-containing paints. RECOMMENDATIONS: The use of lead in paints is completely unregulated in India and routine surveillance of paints for lead content is still lacking. These paints are readily available in markets and are also used in other products (jewelry, miniblinds) which could be exported to other countries including United States and Europe. Serious consideration should be given to the inclusion of regulations and bans on the use of lead in paints. Moreover, attention should also be paid towards the use of various protective measures (face-masks, hand gloves, and separate clothes) by the workers as safe work practices during working periods. PMID- 20300869 TI - Body burdens of polybrominated diphenyl ethers in childbearing-aged women at an intensive electronic-waste recycling site in China. AB - BACKGROUND, AIM AND SCOPE: This study is the first to investigate PBDE body burden with regard to the concurrent analyses of multiple human matrices, namely milk, placenta, and hair, collected from a group of childbearing-aged women at an electronic waste (e-waste) recycling site to determine the partitioning of PBDEs in these different human matrices and the possible health risks imposed to infants at the e-waste recycling site. METHODS AND METHODS: Five sets of milk, placenta, and hair samples were collected from an e-waste site (Taizhou, Zhejiang Province) and a reference site (Lin'an city, Zhejiang Province; 245 km away from Taizhou) in China. The concentrations of total PBDEs in different human tissues were analyzed according to US EPA standard methods. RESULTS: PBDE body burdens of women from the e-waste site (milk 117 +/- 191, 8.89-457 ng/g fat, placenta 19.5 +/- 29.9, 1.28-72.1 ng/g fat, hair 110 +/- 210, 8.47-486 ng/g dry wt.) showed significantly higher levels than those from the reference site (milk 2.06 +/- 0.94, 1.0-3.56 ng/g fat, placenta 1.02 +/- 0.36, 0.59-1.42 ng/g fat, hair 3.57 +/ 2.03, 1.56-5.61 ng/g dry wt.) and were higher than those reported in other studies, due to e-waste recycling operations, especially open burning. On a dry weight basis, the following trend was found for PBDE among the samples from Taizhou: hair>>milk>placenta. Among the donors, the body burden of an e-waste worker ranked second. Higher brominated BDEs (hepta-BDEs) contributed a significantly greater proportion to total PBDEs in hair of the Taizhou women (20%) than that in milk (2.9%) and in placenta (2.6%). The estimated intake of PBDEs of 6-month-old breastfed infants living at the e-waste site was 572 +/- 839 ng/kg body wt/day, which was 57 times higher than that of infants from the reference site (10.1 +/- 4.60 ng/kg body wt/day). Moreover, the maximum calculated value (2,240 ng/kg body wt/day) exceeded the chronic oral reference dose for penta-BDE (2,000 ng/kg/day) of US EPA. DISCUSSION: BDE-47 was the dominant congener accounting for 20-30% in all the individual samples, while higher-brominated congeners, for example, BDE-183 and BDE-190, contributed between 2% and 20%. The presence of hepta-BDE congeners (BDE-181, BDE-190) in hair of the women in Taizhou suggest that thermal degradation of Deca-BDE from the open burning of e-waste may have been their source because these congeners are not found in either Penta-BDE or Octa-BDE technical products. Of the three types of samples analyzed, it was also suspected that hair may be more favorable to higher-brominated compounds which might explain why the hair samples contained the highest total PBDE concentrations and the highest proportion of higher brominated BDEs (hepta-BDEs). CONCLUSION: This study provides evidence that primitive e-waste recycling in China leads to high PBDE body burdens in local residents and can potentially threaten the health of infants. RECOMMENDATIONS AND PERSPECTIVES: Control measures should be imposed to minimize the level of pollutants resulting from e-waste processing operations to the environment and to humans. In-depth investigations on epidemiological studies of health impacts caused by e-waste recycling operations should be conducted. It is recommended that further measurements of PBDE levels in local food (e.g., fish, shellfish, dairy products, meat, fruits, and vegetables), dust, air, water, and human specimens be collected from a larger sample size at the e-waste processing site for the determination of human exposure pathways to PBDEs. PMID- 20300870 TI - Characterization of phenol degradation by high-efficiency binary mixed culture. AB - BACKGROUND, AIM, AND SCOPE: Two new high phenol-degrading strains, Micrococcus sp. and Alcaligenes faecalis JH 1013, were isolated. The two isolates could grow aerobically in mineral salts medium containing phenol as a sole carbon source at concentration of 3,000 mg L(-1). It was found that the binary mixed culture of the two isolates possessed good potential for phenol removal. MATERIAL AND METHODS: Phenol biodegradation using the binary mixed culture of the two isolates was studied. The optimal conditions were determined to be temperature 32 degrees C, pH 7.0, inoculum size 10.0%, and agitation rate 150 rpm in the synthetic wastewater. In addition, the kinetics of the cell growth and phenol degradation by the binary mixed culture were also investigated using Haldane model over a wide range of initial phenol concentrations from 20 to 2,400 mg L(-1). RESULTS: The experimental data indicated that the binary mixed culture had pretty high phenol degradation potential, which could thoroughly degrade the phenol in the synthetic wastewater containing phenol 2,400 mg L(-1) within 72 h under aerobic condition. Under the optimal conditions, the phenol concentration was reduced speedily from 1,000 to below 0.28 mg L(-1) in the presence of the binary mixed culture, and the phenol degradation rate reached 99.97% after 16 h. It was well below the standard value 0.28 mg L(-1) as described by Chinese Environmental Protection Agency. It was clear that the Haldane kinetic model adequately described the dynamic behavior of phenol degradation by the binary mixed culture with kinetic constants of q (max) = 0.45 h(-1), K (sq) = 64.28 mg L(-1), and K (iq) = 992.79 mg L(-1). The phenol concentration to avoid substrate inhibition had been inferred theoretically to be 252.62 mg L(-1). CONCLUSIONS: Phenol, as the only carbon source, could be degraded by the binary mixed culture at high initial phenol concentrations. Phenol exhibited inhibitory behavior, and the growth kinetics of the binary mixed culture could be correlated well by the simple Haldane's inhibitory model. The kinetics parameters were invariably required for the design and simulation of batch and continuous bioreactor treating phenolic wastewaters. PMID- 20300872 TI - Cardiogoniometric parameters for detection of coronary artery disease at rest as a function of stenosis localization and distribution. AB - Cardiogoniometry (CGM), a spatiotemporal electrocardiologic 5-lead method with automated analysis, may be useful in primary healthcare for detecting coronary artery disease (CAD) at rest. Our aim was to systematically develop a stenosis specific parameter set for global CAD detection. In 793 consecutively admitted patients with presumed non-acute CAD, CGM data were collected prior to elective coronary angiography and analyzed retrospectively. 658 patients fulfilled the inclusion criteria, 405 had CAD verified by coronary angiography; the 253 patients with normal coronary angiograms served as the non-CAD controls. Study patients--matched for age, BMI, and gender--were angiographically assigned to 8 stenosis-specific CAD categories or to the controls. One CGM parameter possessing significance (P < .05) and the best diagnostic accuracy was matched to one CAD category. The area under the ROC curve was .80 (global CAD versus controls). A set containing 8 stenosis-specific CGM parameters described variability of R vectors and R-T angles, spatial position and potential distribution of R/T vectors, and ST/T segment alterations. Our parameter set systematically combines CAD categories into an algorithm that detects CAD globally. Prospective validation in clinical studies is ongoing. PMID- 20300871 TI - Zinc tolerance and uptake by Arabidopsis halleri ssp. gemmifera grown in nutrient solution. AB - BACKGROUND, AIM, AND SCOPE: Zinc is an essential micronutrient element but its concentrations found in contaminated soils frequently exceed those required by the plant and soil organisms, and thus create danger to animal and human health. Phytoremediation is a technique, often employed in remediation of contaminated soils, which aims to remove heavy metals or other contaminants from soils or waters using plants. Arabidopsis (A.) halleri ssp. gemmifera is a plant recently found to be grown vigorously in heavy metal contaminated areas of Japan and it contained remarkably high amount of heavy metals in its shoots. However, the magnitude of Zn accumulation and tolerance in A. halleri ssp. gemmifera need to be investigated for its use as a phytoremediation plant. MATERIALS AND METHODS: A. halleri ssp. gemmifera was grown for 3 weeks into half-strength nutrient solution with Zn (as ZnSO(4)) levels ranging from 0.2 to 2,000 microM. The harvested plants were separated into shoots and roots, dried in the oven, and ground. The plant tissue was digested with nitric-perchloric acid, and the Zn concentration in the digested solution was measured by atomic absorption spectrophotometer. RESULTS AND DISCUSSION: The results showed no reduction in shoot and root dry weight when plants were grown at 0.2 to 2,000 microM Zn in the solution. The highest Zn concentration measured in the shoots was 26,400 mg kg( 1) at 1,000 microM Zn, while in the roots, it was 71,000 mg kg(-1) at 2,000 microM Zn treatment. Similar to the Zn concentration in plant parts, maximum Zn accumulation of 62 mg plant(-1) in the shoots and 22 mg plant(-1) in the roots was obtained at 1,000 and 2,000 microM Zn in the solution. The percentage of Zn translocation in shoot varied from 69% to 90% of the total Zn, indicating that the shoot was the major sink of Zn accumulation in this plant. CONCLUSIONS: The results of this study indicate that the growth of A. halleri ssp. gemmifera was not affected by the Zn level of up to 2,000 microM in the nutrient solution. The concentration of Zn found in shoot indicated that A. halleri ssp. gemmifera has an extraordinary ability to tolerate and accumulate Zn and hence a good candidate for the phytoremediation of Zn-polluted soil. RECOMMENDATIONS AND OUTLOOK: Based on the results presented in this study and earlier hydroponics, and field study, A. halleri ssp. gemmifera seems to be a potential heavy metals hyperaccumulator, and could be recommended to use for phytoremediation of Cd- and Zn-contaminated soils. PMID- 20300874 TI - Family caregivers, patients, and physicians. PMID- 20300873 TI - A method for continuously assessing the autonomic response to music-induced emotions through HRV analysis. AB - Interest in therapeutic applications of music has recently increased, as well as the effort to understand the relationship between music features and physiological patterns. In this study, we present a methodology for characterizing music-induced effects on the dynamics of the heart rate modulation. It consists of three steps: (i) the smoothed pseudo Wigner-Ville distribution is performed to obtain a time-frequency representation of HRV; (ii) a parametric decomposition is used to robustly estimate the time-course of spectral parameters; and (iii) statistical population analysis is used to continuously assess whether different acoustic stimuli provoke different dynamic responses. Seventy-five healthy subjects were repetitively exposed to pleasant music, sequences of Shepard tones with the same tempo as the pleasant music and unpleasant sounds overlaid with the same sequences of Shepard tones. Results show that the modification of HRV parameters are characterized by an early fast transient phase (15-20 s), followed by an almost stationary period. All kinds of stimuli provoked significant changes compared to the resting condition, while during listening to pleasant music the heart and respiratory rates were higher (for more than 80% of the duration of the stimuli, p < 10(-5)) and the power of the HF modulation was lower (for more than 70% of the duration of the stimuli, p < 0.05) than during listening to unpleasant stimuli. PMID- 20300875 TI - Lasting sunrise. PMID- 20300876 TI - Fundoplication after laparoscopic Heller myotomy for esophageal achalasia: what type? AB - Because of the high success rate of minimally invasive surgery, a radical shift in the treatment algorithm of esophageal achalasia has occurred. Today, a laparoscopic Heller myotomy is the preferred treatment modality for achalasia. This remarkable change is due to the recognition by gastroenterologists and patients that a laparoscopic Heller myotomy gives better and more durable results than pneumatic dilatation and intrasphincteric injection of botulinum toxin injection, while it is associated to a short hospital stay and a fast recovery time. While there is agreement about the need of a fundoplication in conjunction to the myotomy, some questions still remain about the type of fundoplication: Should the fundoplication be total or partial, and in case a partial fundoplication is chosen, should it be anterior or posterior? The following review describes the data present in the literature in order to identify the best procedure that can achieve prevention or control of gastroesophageal reflux after a myotomy without impairing esophageal emptying. PMID- 20300877 TI - Periampullary and duodenal neoplasms in neurofibromatosis type 1: two cases and an updated 20-year review of the literature yielding 76 cases. AB - BACKGROUND: Patients with neurofibromatosis type 1 (NF1) are at increased risk to develop tumors throughout the gastrointestinal tract, including neuromas, gastrointestinal stromal tumors (GIST), and periampullary somatostatin-rich carcinoids. Here, we briefly describe two male patients with NF1 and review the recent literature on this topic. METHODS: Databases for PubMed and MEDLINE were searched for English-language articles since 1989 using a list of keywords, as well as references from review articles. RESULTS: The results generated by the search yielded 50 articles and 74 cases. Patients most commonly presented with jaundice, weight loss, GI bleeding, or anemia. The mean age at presentation was 47.9 years, with 59% of patients being female. Mean tumor size was 3.8 cm (range 0.9-27 cm). Tumor location was the duodenum (60%), ampulla (31%), pancreas (5%), or bile duct/gallbladder (4%). Tumor type was reported as somatostatinoma (40%), GIST (34%), adenocarcinoma (8%), carcinoid (6%), neurofibroma (5%), schwannoma (4%), or gangliocytic paraganglioma (3%). Treatment included classic Whipple procedure (42%), local excision (25%), pylorus-preserving pancreaticoduodenectomy (17%), and other resection (6%). Mean follow-up was 31 months postresection (range 0-99 months): 75% of patients were alive with no evidence of disease. CONCLUSIONS: These results underscore the importance of a thorough evaluation for tumors in NF1 patients with gastrointestinal symptoms, as well as subsequent surgical management when findings suggest a tumor in the periampullary region, as resection remains the mainstay of treatment. PMID- 20300878 TI - Regression of immunoproliferative small intestinal disease after eradication of Helicobacter pylori. AB - A 20-year-old male presented with low-grade fever, abdominal pain, anorexia, and weight loss of 4-month duration. On examination, he was emaciated. Barium meal follow-through examination showed extensive nodularity and thickening of duodenal and jejunal folds. Contrast-enhanced computed tomography of the abdomen revealed extensive proximal small-bowel thickening with mesenteric lymphadenopathy. Upper gastrointestinal endoscopy and enteroscopy revealed thickening of folds with multiple small superficial ulceration involving antrum, duodenum, and jejunum. The duodenal and jejunal biopsy was suggestive of immunoproliferative small intestinal disease, stage 0 (Salem) or stage A (Galian). Antral biopsy showed presence of Helicobacter pylori infection. He underwent H. pylori eradication following which he had significant clinical improvement; repeat evaluation at 6 months showed dramatic improvement in his clinical, radiological, and histological parameters. PMID- 20300879 TI - Selective outcome reporting: telling and detecting true lies. The state of the science. PMID- 20300880 TI - Endoleak accidentally discovered in congestive heart failure patient. PMID- 20300881 TI - Trichoplusia ni cells (High Five) are highly efficient for the production of influenza A virus-like particles: a comparison of two insect cell lines as production platforms for influenza vaccines. AB - Virus-like particles (VLPs) consisting of the influenza A virus proteins haemagglutinin (HA) and matrix protein (M1) represent a new alternative approach for vaccine design against influenza virus. Influenza VLPs can be fast and easily produced in sufficient amounts in insect cells using the baculovirus expression system. Up to now, influenza VLPs have been produced in the Spodoptera frugiperda cell line Sf9. We compared VLP production in terms of yield and quality in two insect cell lines, namely Sf9 and the Trichoplusia ni cell line BTI-TN5B1-4 (High Five). Additionally we compared VLP production with three different HAs and two different M1s from influenza H1 and H3 strains including one swine-origin pandemic H1N1 strain. Comparison of the two cell lines showed dramatic differences in baculovirus background as well as in yield and particle density. Taken together, we consider the establishment of the BTI-TN5B1-4 cell line advantageous as production cell line for influenza VLPs. PMID- 20300882 TI - Characterization of a monoclonal antibody cell culture production process using a quality by design approach. AB - The goal of quality by design (QbD) in cell culture manufacturing is to develop manufacturing processes which deliver products with consistent critical quality attributes (CQAs). QbD approaches can lead to better process understanding through the use of process parameter risk ranking and statistical design of experiments (DOE). The QbD process starts with an analysis of process parameter risk with respect to CQAs and key performance indicators (KPIs). Initial DOE study designs and their factor test ranges are based on the outcomes of the process parameter risk ranking exercises. Initial DOE studies screen factors for significant influences on CQAs as well as characterize responses for process KPIs. In the case study provided here, multifactor process characterization studies using a scale-down model resulted in significant variation in charge heterogeneity of a monoclonal antibody (MAb) as measured by ion-exchange chromatography (IEC). Iterative DOE studies, using both screening and response surface designs, were used to narrow the operating parameter ranges so that charge heterogeneity could be controlled to an acceptable level. The data from the DOE studies were used to predict worst-case conditions, which were then verified by testing at those conditions. Using the approach described here, multivariate process parameter ranges were identified that yield acceptable CQA levels and that still provide operational flexibility for manufacturing. PMID- 20300883 TI - Utilization of site-specific recombination for generating therapeutic protein producing cell lines. AB - The AttSite Recombinase Technology from Intrexon, Blacksburg, VA, utilizes specific DNA sequences and proprietary recombinase enzymes to catalyze the insertion of a gene of interest at a specific location in the host cell genome. Using this technology, we have developed Chinese Hamster Ovary (CHO) cell lines that have incorporated attB recombination sites at highly transcriptionally active loci or 'hot spots' within the cell genome. Subsequently, these attB site containing host cell lines could then be used for the expression of future Centocor products. Candidate production cell lines would be generated by a simple recombination event. Since the therapeutic gene of interest would preferentially integrate into the pre-selected high-expressing attB site, candidate cell lines would consistently express high levels of the gene of interest. We have been able to demonstrate that the AttSite Recombinase Technology could be a valid approach for the development of high-expressing production cell lines. PMID- 20300885 TI - Comparative studies of various artificial microRNA expression vectors for RNAi in mammalian cells. AB - Artificial microRNA (amiRNA) has recently become an important RNA interference (RNAi) technology for gene therapy and gene function studies. Here nine expression strategies were employed to construct plasmid vectors expressing amiRNA (amiR-Fluc) against firefly luciferase (Fluc). Our results indicate that all nine vectors can successfully produce mature amiR-Fluc and specifically suppress the expression of Fluc, although the RNAi efficiency in different mammalian cells displays obvious differences. Among these nine vectors, three can efficiently co-express DsRed reporter gene linked with amiR-Fluc cassette. Moreover, the recommended number of concatenated amiRNAs in a multi-amiRNA expression vector should not be more than four, and the relative position of an amiRNA in the multi-amiRNA expression vector has no apparent influence on its RNAi activity. In summary, all these results described here provide valuable information for the rational design and application of amiRNA expression vector. PMID- 20300886 TI - Characterization of enzymes in the oxidation of 1,2-propanediol to D: -(-)-lactic acid by Gluconobacter oxydans DSM 2003. AB - Although Gluconobacter oxydans can convert 1,2-propanediol to D: -(-)-lactic acid, the enzyme(s) responsible for the conversion has remain unknown. In this study, the membrane-bound alcohol dehydrogenase (ADH) of Gluconobacter oxydans DSM 2003 was purified and confirmed to be essential for the process of D: -(-) lactic acid production by gene knockout and complementation studies. A 25 percent decrease in D: -(-)-lactic acid production was found for the aldehyde dehydrogenase (ALDH) deficient strain of G. oxydans DSM 2003, indicating that this enzyme is involved in the reaction but not necessary. It is the first report that reveals the function of ADH and ALDH in the biooxidation of 1,2-propanediol to D: -(-)-lactic acid by G. oxydans DSM 2003. PMID- 20300884 TI - Structure and basal transcription complex of RNA polymerase II core promoters in the mammalian genome: an overview. AB - The mammalian core promoter is a sophisticated and crucial component for the regulation of transcription mediated by the RNA polymerase II. It is generally defined as the minimal region of contiguous DNA sequence that is sufficient to accurately initiate a basal level of gene expression. The core promoter represents the ultimate target for nucleation of a functional pre-initiation complex composed of the RNA polymerase II and associated general transcription factors. Among the more than 40 distinct proteins assembling the basal transcription complex, TFIID plays a central role in recognizing and binding specific core promoter elements to support creating an environment that facilitates transcription initiation. Several common DNA motifs, like the TATA box, initiator region, or the downstream promoter element, are found in a subset of core promoters present in various combinations. Another class of promoters that is usually absent of a TATA box is constituted by the so-called CpG islands, which are associated with the majority of protein-coding genes within the mammalian genome. PMID- 20300887 TI - Stem/precursor cell-based CNS therapy: the importance of circumventing immune suppression by transplanting autologous cells. AB - Stem/precursor cell (SPC) therapy for neurodegeneration and neurotrauma has enormous therapeutic potential, but despite ongoing research efforts the success of clinical trials remains limited. Therapies that utilize immune suppression in combination with SPC transplantation have thus far failed to consider the beneficial role of the immune system in central nervous system (CNS) recovery. Systemic immune suppression may prevent neural repair, and in some cases exacerbate the underlying disorder. Until about a decade ago, immunosuppression for CNS disorders was viewed as a therapeutic target, based on the perception that all immune activity in the CNS was destructive. However, recent studies show that the infiltration of blood-borne immune cells into the CNS following neurotrauma and during chronic neurodegeneration promote CNS protection and regeneration. In the context of SPC therapies, although immune suppression prevents rejection of non-autologous cell grafts, it also prevents the restorative immune response by eliminating the immune mediated guidance cues that are required for SPCs to migrate to the location they are needed, and preventing SPC-mediated immunomodulation. This article argues in favor of transplanting autologous SPCs, particularly bone marrow derived cells. The therapeutic use of autologous SPCs for neural repair circumvents the need for concomitant immune suppression, exploits the immunomodulatory capacity of these cells, and maintains the immune niche that supports neural repair and is required to guide these cells to their appropriate locations. Overall, such an approach accommodates the requirements for translational therapeutics, and provides a standardized platform for reconciling the inherent controversies in the science. PMID- 20300889 TI - The use of commercial alcohol products to sterilize bones prior to DNA sampling. AB - In disaster situations it is not always possible to maintain an adequate supply of standard equipment and sterilizing solutions. We have compared bone samples from cadavers cleaned in commercial white alcohol to samples from the same individuals cleaned with 95% surgical spirit. We have found that it is possible to use a commercial, white spirit to clean specimens taken from human cadavers femoral diaphysis collected for DNA analysis. PMID- 20300890 TI - 1H, 13C and 15N assignment of the C-terminal domain of GNA2132 from Neisseria meningitidis. AB - GNA2132 (Genome-derived Neisseria Antigen 2132) is a surface-exposed lipoprotein discovered by reverse vaccinology and expressed by genetically diverse Neisseria meningitidis strains (Pizza et al. 2000). The protein induces bactericidal antibodies against most strains of Meningococccus and has been included in a multivalent recombinant vaccine against N. meningitidis serogroup B. Structure determination of GNA2132 is important for understanding the antigenic properties of the protein in view of increased efficiency vaccine development. We report practically complete (1)H, (13)C and (15)N assignment of the detectable spectrum of a highly conserved C-terminal region of GNA2132 (residues 245-427) in micellar solution, a medium used to improve the spectral quality. The first 32 residues of our construct up to residue 277 were not visible in the spectrum, presumably because of line broadening due to solvent and/or conformational exchange. Secondary structure predictions based on chemical shift information indicate the presence of an all beta-protein with eight beta strands. PMID- 20300888 TI - Risks and mechanisms of oncological disease following stem cell transplantation. AB - Unique biological properties of stem cells make them a precious source of cell material for treatment of a number of pathological conditions. Among issues inhibiting transition of stem cell technologies to the clinics, the risk of oncological complications of stem cell-based therapies is the most critical. A massive amount of clinical and experimental data demonstrates that both hematological (including acute and chronic myeloid leukemia) and non hematological (including teratoma and non-teratoma tumors) malignancies could arise from donor stem cells of different types. A wide spectrum of mechanisms could underlie the development of oncological disease in recipients, including: i) blast transformation of proliferating donor stem cells under persistent action of certain factors in the recipient, thus causing de novo malignancies; ii) contamination of donor cell material with malignant cells; iii) transmission of particular viral subtypes with donor stem cells, combined with immunosuppression therapy effects; iv) uncontrollable proliferation of residual undifferentiated stem cells of various plasticity; and v) karyotypic instability in stem cells following prolonged culturing/expansion in vitro. Potential preventive strategies are diverse and include i) high-throughput cell sorting-based strategies; ii) introduction of suicide genes into the donor stem cell genome; iii) application of apoptosis-inducing epigenetic factors; and some other options. PMID- 20300891 TI - Backbone 1H, 13C, and 15N resonance assignments for lysozyme from bacteriophage lambda. AB - Lysozyme from lambda bacteriophage (lambda lysozyme) is an 18 kDa globular protein displaying some of the structural features common to all lysozymes; in particular, lambda lysozyme consists of two structural domains connected by a helix, and has its catalytic residues located at the interface between these two domains. An interesting feature of lambda lysozyme, when compared to the well characterised hen egg-white lysozyme, is its lack of disulfide bridges; this makes lambda lysozyme an interesting system for studies of protein folding. A comparison of the folding properties of lambda lysozyme and hen lysozyme will provide important insights into the role that disulfide bonds play in the refolding pathway of the latter protein. Here we report the (1)H, (13)C and (15)N backbone resonance assignments for lambda lysozyme by heteronuclear multidimensional NMR spectroscopy. These assignments provide the starting point for detailed investigation of the refolding pathway using pulse-labelling hydrogen/deuterium exchange experiments monitored by NMR. PMID- 20300892 TI - Assignment of the orphan nuclear receptor Nurr1 by NMR. AB - The orphan nuclear receptor Nurr1 has been implicated in a number of conditions including Parkinson's disease and Schizophrenia. As such, it is of interest to study its interactions with other proteins, possibly mediated by small molecules, considering possible use as a drug target. We produced (2)H, (15)N, (13)C labelled-Nurr1 to generate the backbone amide NH, carbonyl C', C(alpha) and C(beta) assignments. About 84.0% of residues could be assigned. Most of the 37 missing assignments fall in 3 regions of the protein. Two of these surround a putative ligand-binding region of Nurr1, suggesting that this region of the protein is flexible, despite the ligand-binding pocket being filled with hydrophobic side-chains from residues surrounding the ligand binding pocket. PMID- 20300893 TI - Validity of a power law approach to model tablet strength as a function of compaction pressure. AB - Designing quality into dosage forms should not be only based on qualitative or purely heuristic relations. A knowledge space must be generated, in which at least some mechanistic understanding is included. This is of particular interest for critical dosage form parameters like the strength of tablets. In line with this consideration, the scope of the work is to explore the validity range of a theoretically derived power law for the tensile strength of tablets. Different grades of microcrystalline cellulose and lactose, as well as mixtures thereof, were used to compress model tablets. The power law was found to hold true in a low pressure range, which agreed with theoretical expectation. This low pressure range depended on the individual material characteristics, but as a rule of thumb, the tablets having a porosity of more than about 30% or being compressed below 100 MPa were generally well explained by the tensile strength relationship. Tablets at higher densities were less adequately described by the theory that is based on large-scale heterogeneity of the relevant contact points in the compact. Tablets close to the unity density therefore require other theoretical approaches. More research is needed to understand tablet strength in a wider range of compaction pressures. PMID- 20300894 TI - Evaluation of chitosan/alginate beads using experimental design: formulation and in vitro characterization. AB - Bovine serum albumin-loaded beads were prepared by ionotropic gelation of alginate with calcium chloride and chitosan. The effect of sodium alginate concentration and chitosan concentration on the particle size and loading efficacy was studied. The diameter of the beads formed is dependent on the size of the needle used. The optimum condition for preparation alginate-chitosan beads was alginate concentration of 3% and chitosan concentration of 0.25% at pH 5. The resulting bead formulation had a loading efficacy of 98.5% and average size of 1,501 mum, and scanning electron microscopy images showed spherical and smooth particles. Chitosan concentration significantly influenced particle size and encapsulation efficiency of chitosan-alginate beads (p < 0.05). Decreasing the alginate concentration resulted in an increased release of albumin in acidic media. The rapid dissolution of chitosan-alginate matrices in the higher pH resulted in burst release of protein drug. PMID- 20300895 TI - A review of multi-responsive membranous systems for rate-modulated drug delivery. AB - Membrane technology is broadly applied in the medical field. The ability of membranous systems to effectively control the movement of chemical entities is pivotal to their significant potential for use in both drug delivery and surgical/medical applications. An alteration in the physical properties of a polymer in response to a change in environmental conditions is a behavior that can be utilized to prepare 'smart' drug delivery systems. Stimuli-responsive or 'smart' polymers are polymers that upon exposure to small changes in the environment undergo rapid changes in their microstructure. A stimulus, such as a change in pH or temperature, thus serves as a trigger for the release of drug from membranous drug delivery systems that are formulated from stimuli-responsive polymers. This article has sought to review the use of stimuli-responsive polymers that have found application in membranous drug delivery systems. Polymers responsive to pH and temperature have been extensively addressed in this review since they are considered the most important stimuli that may be exploited for use in drug delivery, and biomedical applications such as in tissue engineering. In addition, dual-responsive and glucose-responsive membranes have been also addressed as membranes responsive to diverse stimuli. PMID- 20300896 TI - Modulation of tramadol release from a hydrophobic matrix: implications of formulations and processing variables. AB - In the present investigation, hydrogenated cottonseed oil (HCSO) was evaluated as a sustained release matrix for a freely soluble drug, tramadol. Hydrophobic matrix tablets of tramadol, was evaluated by compression of physical mixture of drug and wax, dispersion of drug in HCSO by hot fusion or solubilisation techniques. The method of preparation of tablet had a significant effect on drug release with higher release observed from direct compression matrices and slower release from matrix prepared by dispersion (hot-fused matrices). Influence of addition of hydroxypropylmethyl cellulose, sodium carboxymethyl cellulose, polyethylene glycol 4000 and surfactants like sodium lauryl sulphate and polysorbate 20 to HCSO matrix on drug release was investigated. The added excipients exhibited a propensity to enhance drug release from the HCSO matrix. NaCMC was effective at a lower ratio (<10% w/w) and when incorporated at higher level made HCSO matrix to erode and disintegrate in a short period. PMID- 20300897 TI - The effects of rosuvastatin on the serum cortisol, serum lipid, and serum mevalonic acid levels in the healthy Indian male population. AB - In this open-label, balanced, randomized, placebo-controlled, parallel study, healthy male volunteers were randomly divided into two groups. Each group received either a single oral dose of rosuvastatin 20 mg or placebo. Estimations were done at predose on day 1 of dosing (baseline) and 24 h postdose after days 7 and 14. Serum cortisol and serum lipid levels were estimated using enzyme-linked immunosorbent assay kits and serum mevalonic acid (MVA) levels were measured using validated liquid chromatography-tandem mass spectrometry method. Rosuvastatin produced a statistically significant (P < 0.05) decrease in total cholesterol, low-density lipoprotein cholesterol, very low-density lipoprotein cholesterol, and triglycerides. However, the increase in high-density lipoprotein cholesterol and decrease in cortisol and MVA were not statistically significant when compared to the placebo-treated group. The study showed that rosuvastatin at a dose of 20 mg/day for a period of 14 days was very potent as cholesterol lowering agent, without any significant change in serum cortisol level in the healthy Indian male population. PMID- 20300898 TI - Buccal drug delivery of pravastatin sodium. AB - The purpose of this study was to develop and optimize formulations of mucoadhesive bilayered buccal tablets of pravastatin sodium using carrageenan gum as the base matrix. The tablets were prepared by direct compression method. Polyvinyl pyrrolidone (PVP) K 30, Pluronic(R) F 127, and magnesium oxide were used to improve tablet properties. Magnesium stearate, talc, and lactose were used to aid the compression of tablets. The tablets were found to have good appearance, uniform thickness, diameter, weight, pH, and drug content. A 2(3) full factorial design was employed to study the effect of independent variables viz. levels of carrageenan gum, Pluronic F 127 and PVP K30, which significantly influenced characteristics like in vitro mucoadhesive strength, in vitro drug release, swelling index, and in vitro residence time. The tablet was coated with an impermeable backing layer of ethyl cellulose to ensure unidirectional drug release. Different penetration enhancers were tried to improve the permeation of pravastatin sodium through buccal mucosa. Formulation containing 1% sodium lauryl sulfate showed good permeation of pravastatin sodium through mucosa. Histopathological studies revealed no buccal mucosal damage. It can be concluded that buccal route can be one of the alternatives available for the administration of pravastatin sodium. PMID- 20300899 TI - Case report: Spinal anesthesia by mini-laminotomy for a patient with ankylosing spondylitis who was difficult to anesthetize. AB - BACKGROUND: Orthopaedic surgeons frequently encounter patients with ankylosing spondylitis who would benefit from various types of lower limb operations; however, some of these patients present challenges for anesthesiologists. CASE DESCRIPTION: We report the case of a 65-year-old patient with a fractured femoral component 30 years after a cemented THA. The patient had severe tracheal stenosis and ankylosing spondylitis making general endotracheal and conventional neuraxial anesthesia nearly impossible. LITERATURE REVIEW: Possible alternative anesthetic approaches described in the literature include awake fiberoptic bronchoscopic guided intubation, laryngeal mask airway, and caudal anesthesia. PURPOSES AND CLINICAL RELEVANCE: We achieved successful anesthesia using spinal laminotomy with the patient under local anesthesia followed by insertion of a spinal catheter and injection of an anesthetic agent. The loosened component was revised to a cementless THA. PMID- 20300900 TI - Routine surveillance of modular PFC TKA shows increasing failures after 10 years. AB - BACKGROUND/RATIONALE: A 10-year survivorship of 100% was reported for patients with PFC cruciate-retaining prostheses. Beyond 10 years, we observed additional polyethylene wear likely related to thin liners gamma-irradiated in air and were concerned this wear might predispose to implant construct failure. QUESTIONS/PURPOSES: We therefore determined (1) the functional scores at a minimum of 15 years followup, (2) rates of radiographic failure, (3) overall revision rates, and (4) mode of failure after 10 years and the fate of the revised implants. METHODS: We retrospectively reviewed 75 patients with 101 press fit condylar posterior cruciate-retaining prostheses. At a minimum followup of 15 years, 35 patients (47 knees) were living and evaluated clinically. No patients were lost to followup. RESULTS: There were no revisions during the first 11 years and six reoperations subsequently were performed in five patients (6% overall rate of revision but 12.8% in patients who survived more than 15 years). Three of six revisions had concerning liner wear at 10 years and all six were revised for polyethylene wear. Polyethylene exchange was performed in four of the five patients who underwent revisions, all of whom were doing well at an average of 7.2 years (range, 4.7-9.1 years) after the revision procedure. CONCLUSIONS: At long-term followup, the overall revision rate remained low (6%). For patients surviving 15 years or more, the rate of revision was 12.8% and all revisions were secondary to aseptic sequelae of polyethylene wear. All revisions occurred more than 10 years after the initial procedures. LEVEL OF EVIDENCE: Level IV, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence. PMID- 20300901 TI - Synovial fluid biomarkers for periprosthetic infection. AB - BACKGROUND: We have previously described a unique gene expression signature exhibited by synovial fluid leukocytes in response to bacterial infection, identifying a number of potential biomarkers for infection. However, the diagnostic performance of these potential biomarkers in an immunoassay format is unknown. QUESTIONS/PURPOSES: We therefore evaluated the sensitivity, specificity, and accuracy of several potential synovial fluid biomarkers for infection, and compared them to current standards of testing for periprosthetic infection. METHODS: We prospectively collected synovial fluid from 14 patients classified as having a periprosthetic infection and 37 patients classified as having an aseptic failure. The synovial fluid samples were tested for 23 potential biomarkers for periprosthetic infection. We then determined differences in biomarker levels between infected and aseptic groups, then computed the sensitivity, specificity, positive predictive value, negative predictive value and accuracy for select biomarkers, and finally compared those to current standard tests for infection. RESULTS: Twelve synovial fluid biomarkers had substantially higher average levels in the synovial fluid of infected versus aseptic patients. Synovial fluid levels of IL-1 were a mean of 258 times higher in patients with a periprosthetic infection compared to patients having revision for aseptic diagnoses. Synovial fluid IL-1 and IL-6 levels correctly classified all patients in this study with a sensitivity, specificity, positive predictive value, negative predictive value and accuracy equal to 1. Several markers tested in this study outperformed the ESR and CRP tests. CONCLUSIONS: Patients with a periprosthetic infection have elevated levels of numerous synovial fluid biomarkers, when compared to patients with aseptic diagnoses. Several of these biomarkers exhibited nearly ideal sensitivity, specificity, and accuracy in this study, suggesting that synovial fluid biomarkers could be a valuable tool for diagnosing periprosthetic infection. LEVEL OF EVIDENCE: Level III, prognostic study. See Guidelines for Authors for a complete description of levels of evidence. PMID- 20300902 TI - Case report: Mesenchymal chondrosarcoma of the lumbar spine in a child. AB - BACKGROUND: Chondrosarcomas of the spine constitute 4% to 10% of all primary spinal bone tumors and approximately 70% of the cases occur during the second or third decade of life. Mesenchymal chondrosarcoma is a rare aggressive variant of chondrosarcoma. The prognosis of mesenchymal chondrosarcoma is usually poor with a tendency for late local recurrence and metastasis. CASE DESCRIPTION: We describe a case of primary mesenchymal chondrosarcoma affecting the L5 vertebra of a 9-year-old girl. The patient underwent a staged circumferential resection of the tumor after three rounds of neoadjuvant chemotherapy. The patient had additional chemotherapy and radiation therapy as an intralesional margin was achieved during the procedure. At 9 years followup, the patient was asymptomatic, neurologically intact, and remained in remission. LITERATURE REVIEW: We identified only four previously published cases of spinal mesenchymal chondrosarcoma in childhood, two of which had relatively early recurrence and poor survival, and two survived but with only short followup. PURPOSES AND CLINICAL RELEVANCE: As the clinical and radiographic findings of mesenchymal chondrosarcoma are nonspecific, the diagnosis of this rare tumor requires careful histopathologic review of the specimens. We suggest the differential diagnosis of every primary intraspinal tumor include tumors of mesenchymal origin. The prognosis is apparently not uniformly poor. PMID- 20300903 TI - Two-stage exchange knee arthroplasty: does resistance of the infecting organism influence the outcome? AB - BACKGROUND: Periprosthetic joint infection after TKA is a challenging complication. Two-stage exchange arthroplasty is the accepted standard of care, but reported failure rates are increasing. It has been suggested this is due to the increased prevalence of methicillin-resistant infections. QUESTIONS/PURPOSES: We asked the following questions: (1) What is the reinfection rate after two stage exchange arthroplasty? (2) Which risk factors predict failure? (3) Which variables are associated with acquiring a resistant organism periprosthetic joint infection? METHODS: This was a case-control study of 102 patients with infected TKA who underwent a two-stage exchange arthroplasty. Ninety-six patients were followed for a minimum of 2 years (mean, 34.5 months; range, 24-90.1 months). Cases were defined as failures of two-stage exchange arthroplasty. RESULTS: Two stage exchange arthroplasty was successful in controlling the infection in 70 patients (73%). Patients who failed two-stage exchange arthroplasty were 3.37 times more likely to have been originally infected with a methicillin-resistant organism. Older age, higher body mass index, and history of thyroid disease were predisposing factors to infection with a methicillin-resistant organism. CONCLUSIONS: Innovative interventions are needed to improve the effectiveness of two-stage exchange arthroplasty for TKA infection with a methicillin-resistant organism as current treatment protocols may not be adequate for control of these virulent pathogens. LEVEL OF EVIDENCE: Level IV, prognostic study. See Guidelines for Authors for a complete description of levels of evidence. PMID- 20300905 TI - Exploring the role of the built and social neighborhood environment in moderating stress and health. AB - BACKGROUND: Health researchers have explored how different aspects of neighborhood characteristics contribute to health and well-being, but current understanding of built environment factors is limited. PURPOSE: This study explores whether the association between stress and health varies by residential neighborhood, and if yes, whether built and social neighborhood environment characteristics act as moderators. METHODS: This study uses multilevel modeling and variables derived from geospatial data to explore the role of neighborhood environment in moderating the association of stress with health. Individual-level data (N = 4,093) were drawn from residents of 45 neighborhoods within Philadelphia County, PA, collected as part of the 2006 Philadelphia Health Management Corporation's Household Health Survey. RESULTS: We find that the negative influence of high stress varied by neighborhood, that residential stability and affluence (social characteristics) attenuated the association of high stress with health, and that the presence of hazardous waste facilities (built environment characteristics) moderated health by enhancing the association with stress. CONCLUSIONS: Our findings suggest that neighborhood environment has both direct and moderating associations with health, after adjusting for individual characteristics. The use of geospatial data could broaden the scope of stress-health research and advance knowledge by untangling the intertwined relationship between built and social environments, stress, and health. In particular, future studies should integrate built environment characteristics in health-related research; these characteristics are modifiable and can facilitate health promotion policies. PMID- 20300906 TI - Impact of weight on long-term survival among patients without known coronary artery disease and a normal stress SPECT MPI. AB - BACKGROUND: While obesity has been shown to be associated with a worse mortality, an "obesity paradox"--lower mortality in obese patients--has been noted among many patients with coronary artery disease (CAD). The extent to which an obesity paradox operates among patients with only suspected CAD, is not well determined. METHODS AND RESULTS: A total of 3,673 patients (60 +/- 13 years, 36% males) with no history of heart disease and a normal stress SPECT were included in this study. Normal weight was defined as BMI of 18.5-24.9 kg x m(2); overweight 25 29.9 kg . m(2), obese >30 kg x m(2). The baseline clinical risk factors were recorded for each patient. The end point of the study was all-cause mortality. Of patients 942 (26%) were normal weight, 1,261 (34%) were overweight, and 1,470 (40%) were obese. Mean patient follow-up was 7.5 +/- 3 years. When compared to normal weight patients (event rate 3.2%/year), there was a lower incidence of death in the overweight (event rate 1.5%/year, P < .0001) and the obese (event rate 1.2%/year, P < .0001) groups. After controlling for baseline risk factors, using a reference HR = 1 for normal weight patients, there was a lower risk of death in the overweight (HR = .54, 95% CI .43-.7) and the obese groups (HR = .49, 95% CI .38-.63). CONCLUSION: In patients without known cardiac disease and a normal stress SPECT, overweight and obese patients had a lower rate of all-cause mortality compared to normal weight patients over long-term follow-up. This study substantially extends the spectrum of patients in whom the obesity paradox is present. PMID- 20300908 TI - Is preoperative opioid utilization an important factor in predicting phantom limb pain? PMID- 20300907 TI - Relation of left-ventricular dyssynchrony by phase analysis of gated SPECT images and cardiovascular events in patients with implantable cardiac defibrillators. AB - BACKGROUND: Left-ventricular (LV) dyssynchrony could be measured by gated SPECT myocardial perfusion imaging (MPI). This study examined the relation between the degree of dyssynchrony and outcome in patients with implantable cardiac defibrillators (ICDs). METHODS AND RESULTS: We studied 70 patients with ICD and LV ejection fraction (EF) <.40 by gated MPI (performed within 6 weeks of the device implantation). The images were re-processed using phase analysis to derive phase standard deviation (SD) and histogram bandwidth. All-cause mortality and appropriate ICD shocks were identified as the primary endpoint. There were 87% men, aged 62 +/- 11 years. The EF was 26 +/- 8% (range 12%-39%). The phase SD was 51 degrees +/- 20 degrees (range 12 degrees -99 degrees ) and the histogram bandwidth was 157 degrees +/- 72 degrees (range 21 degrees -327 degrees ). The SD and bandwidth were significantly greater than corresponding values in patients with normal EF (15.8 +/- 11.8 degrees and 42.0 +/- 28.4 degrees , respectively, P < .0001, each). At 1 year, 8 patients (11%) died or had shocks. The patients with events had higher phase SD than those without events (60 +/- 5 degrees vs 50 +/- 21 degrees , P = .002). The histogram bandwidth was also higher in those with events (185 +/- 37 vs 154 +/- 75, P = .07). All patients with event had a phase SD >or= 50 degrees , while none of the patients with a phase SD < 50 degrees (N = 26) had an event (P = .02). CONCLUSIONS: The severity of LV dyssynchrony by phase analysis in patients with LV dysfunction, and ICD is associated with increased risk of death and appropriate ICD shock; a phase SD < 50 degrees was associated with no events at 1 year. PMID- 20300910 TI - The impact of a primetime cancer storyline: from individual knowledge and behavioral intentions to policy-level changes. AB - We assessed the educational impact of a primetime network TV storyline that addressed cancer patient navigators. An online survey was administered after the episode aired. Exposed respondents saw the episode (n = 336); unexposed respondents did not (n = 211). Exposed respondents were more likely to report they would recommend a patient navigator (61% vs. 48%, p = 0.01). Clips of the episode were shown to raise awareness of patient navigators in a Congressional Committee meeting before the Patient Navigator Act was signed into law (2005). Entertainment education can have a positive impact on cancer knowledge and can contribute to policy-level decisions. PMID- 20300909 TI - Physical exercise attenuates MPTP-induced deficits in mice. AB - Two experiments were performed to investigate the effects of physical exercise upon the hypokinesia induced by two different types of MPTP administration to C57/BL6 mice. In the first, mice were administered either the standard MPTP dose (2 * 20 or 2 * 40 mg/kg, 24-h interval) or vehicle (saline, 5 ml/kg); and over the following 3 weeks were given daily 30-min period of wheel running exercise over five consecutive days/week or placed in a cage in close proximity to the running wheels. Spontaneous motor activity testing in motor activity test chambers indicated that exercise attenuated the hypokinesic effects of both doses of MPTP upon spontaneous activity or subthreshold L: -Dopa-induced activity. In the second experiment, mice were either given wheel running activity on four consecutive days (30-min period) or placed in a cage nearby and on the fifth day, following motor activity testing over 60 min, injected with either MPTP (1 * 40 mg/kg) or vehicle. An identical procedure was maintained over the following 4 weeks with the exception that neither MPTP nor vehicle was injected after the fifth week. The animals were left alone (without either exercise or MPTP) and tested after 2- and 4-week intervals. Weekly exercise blocked, almost completely, the progressive development of severe hypokinesia in the MPTP mice and partially restored normal levels of activity after administration of subthreshold L: -Dopa, despite the total absence of exercise following the fifth week. In both experiments, MPTP-induced loss of dopamine was attenuated by the respective regime of physical exercise with dopamine integrity more effectively preserved in the first experiment. The present findings are discussed in the context of physical exercise influences upon general plasticity and neuroreparative propensities as well as those specific for the nigrostriatal pathway. PMID- 20300911 TI - Multilayer and multimetric quality control: the Supercourse. AB - Cancer-related presentations are rapidly communicated through thousands of Websites, chat rooms, newsgroups, list servers, newsletters, YouTube, and e mails, with no specific attention to the validity of the reported findings. Quality control (QC) of cancer education lectures on the Web is an important concern, just like the quality assessment of all information found on the Web. This paper discusses the Supercourse, a global library of 3,600 online lectures available at www.pitt.edu/~super1 and several alternative quality control approaches that are being developed as part of this global effort. Peer review may not be optimal for the review of online lectures because it is labor intensive and has low throughput. To our knowledge, we are among the first to begin a multilayer and multimetric evaluation approach toward QC (MQC) of PowerPoint lectures on the Web. We hope that future scientific research on peer review as well as on emerging multilayer QC methodologies will help us to determine best measures of QC, especially in the field of rapidly developing cancer education. PMID- 20300912 TI - Educational intervention among barbers about liver cancer-inducing viruses: a pilot study from a developing country. AB - Liver cancer is among the most prevalent cancers in the world and it is mainly related to the hepatitis B virus (HBV) and hepatitis C virus (HCV). This study evaluated the effectiveness of educational intervention on knowledge and practices regarding hepatitis B and hepatitis C among barbers. After completion of baseline interviews of 70 barbers in Karachi, Pakistan, a 30-min educational session was conducted. The same sessions were repeated twice for all barbers at an interval of 1 month each for reinforcement. Post-intervention interviews were conducted after 1 month of the last session. Before intervention, only 11.4% of the study participants had scored "good" about the knowledge of HBV, which improved to 74.3% after intervention (p < 0.001). Similarly, for HCV, significant improvement was observed after intervention. Regarding the safe practices to prevent HBV and HCV infections, <2% had scored to the level of "good" at baseline, which improved to 48.6% after intervention (p < 0.001). Educational interventions to prevent cancer-induced viruses are highly effective even in illiterate/low-educated people. PMID- 20300913 TI - Development and validation of a nutritional education pamphlet for low literacy pediatric oncology caregivers in Central America. AB - A culturally appropriate nutrition education pamphlet was developed and validated for low-literacy caregivers in Honduras, El Salvador, and Guatemala. The pamphlet was developed after a preliminary survey of pediatric oncology nurses in the 3 countries to assess the need for education materials, caregiver literacy levels, and local eating habits. Experts in nutrition and low-literacy patient education and pediatric oncology nurses validated the pamphlet's content and design. The pamphlet was validated positively and has been circulated to pediatric oncology caregivers in Central America. PMID- 20300914 TI - Breast screening navigator programs within three settings that assist underserved women. AB - Medically underserved women in the Greater Denver Metropolitan Area had low rates of routine repeat mammograms in the latter 1990s. "Increasing Mammography Adherence among Medically Underserved Women" was designed to increase annual rescreening among medically underserved populations living in this area. Four community-based organizations collaborated to implement this 5-year study. A culturally modified navigator model including both face-to-face and telephone formats was used to facilitate mammography for African Americans, Latinas, Native Americans, and poor White women who had not been rescreened in more than 18 months. The navigator-implemented intervention was statistically significant at the 0.05 level for increasing rescreening. PMID- 20300915 TI - African American's self-report patterns using the National Cancer Institute Colorectal Cancer Screening questionnaire. AB - Studies that examine colorectal cancer screening (CRCS) behaviors and correlates rely on self-reports of screening status. Self-reports of CRCS may be more biased than other self-reported cancer screening because of multiple screening options, tests may be offered in combination, and screening schedules differ for each test. The National Cancer Institute (NCI) sponsored the development of a core set of questions to measure self-reported CRCS that are consistent with current guidelines, the NCI Colorectal Cancer Screening questionnaire (NCI CRCS). Several studies support the validity and reliability of this measure; however, none of the existing studies have described African American (AA) responses to items that might be important to clinical decision making and research related to screening adherence. This paper addresses the limited descriptions of AA response patterns to items that comprise the NCI CRCS. The NCI CRCS was administered to 439 AAs 50 to 75 years, participating in the baseline survey of a Center for Excellence in Cancer Communication CRC study. The survey measured self-reported CRCS, factors associated with screening, and response patterns to items that might affect estimates of screening and screening adherence. AA participants reported on CRCS, the test used, and time interval since last screening. Except for queries related to month and year of screening, few participants reported uncertainty in response to items. Two thirds of participants reported receiving CRCS; however, less than half of participants were adherent to guidelines. Less than half reported healthcare provider recommendations to screen. AA participants responded to items on the NCI CRCS as developed. Until new strategies or items are available, interval since last screening appears to be the most appropriate item to estimate AA self-reported CRCS adherence. Strategies are needed to increase physician recommendation to screen. PMID- 20300916 TI - Seeking to bridge two cultures: the Wisconsin Hmong cancer experience. AB - Compared to white non-Hispanics, Hmong report higher incidence rates of certain cancers and present at an advanced stage. Using a community-based participatory research approach, Hmong leaders partnered with academic researchers to assess the Wisconsin Hmong population's readiness to address cancer. Using the Colorado Tri-Ethnic Center's Community Readiness Assessment, face-to-face interviews were conducted with eight Hmong leaders. The stage of readiness to address cancer was "Vague Awareness". Six thematic areas provided insight into this stage and recommendations for effective intervention. Results emphasize the need for a bridge between Hmong and mainstream communities to provide basic, culturally appropriate education on the US healthcare system and cancer. PMID- 20300917 TI - MMP-7 overexpression is an independent prognostic marker in gastric cancer. AB - To enable cancer to invade and to metastasize, the surrounding stroma must be degraded. Matrix metalloproteinase-7 (MMP-7) is capable of degrading many extracellular matrix proteins and cellular adhesions, is overexpressed in many malignancies, and plays a role in tumour progression. The purpose of this study was to evaluate the association between MMP-7 tissue expression and patients' prognosis in gastric cancer. From 264 patients who underwent surgery for gastric cancer, surgical specimens were collected on tissue array blocks and stained by immunohistochemistry for MMP-7. In 27 (10.2%) of the specimens, immunopositivity was found as high, in 50 (18.9%) as moderate and in 51 (19.3%) as weak. In 136 cases (51.5%), the immunopositivity was negative. A statistically significant correlation appeared between high MMP-7 expression and poor survival. In conclusion, our results suggest that MMP-7 expression may prove helpful in evaluating gastric cancer prognosis. PMID- 20300920 TI - [Training palliative care in Austria - empathy combined with science - the 3rd intensive course of palliative medicine]. PMID- 20300918 TI - Brain damage in a large cohort of solvent abusers. AB - The neuropathology of solvent inhalation consists of patchy myelin loss with white matter macrophages that contain granular inclusions. It has been described only in a small number of cases. We sought to characterize the abnormalities in greater detail. In a retrospective study from 1995 to 2009, we encountered 88 autopsy cases with documented history of solvent abuse by inhalation and 1 with industrial exposure. Among these are 6 fetuses and infants with maternal exposure, 23 children (12-17 years), and 60 adults (18-66 years). Available brain samples from 75 cases were stained with solochrome cyanein (to demonstrate myelin) and periodic acid-Schiff (PAS) (to highlight the inclusions). Forty brains of ethanol and/or illicit drug exposed individuals and ten cases of multiple sclerosis were examined as controls. We found that 16 cases (age 23-49, median 37 years) had well-established leukoencephalopathy with multifocal myelin loss and abundant macrophages that stain with PAS and which contain birefringent inclusions. Six cases (age 15-55, median 27 years) had early leukoencephalopathy with scattered macrophages but no obvious myelin changes. Clusters of PAS staining but non-birefringent macrophages were seen in 2/10 cases of (active) multiple sclerosis and in none of the ethanol/drug exposed brains. Ultrastructurally, inclusions from solvent cases differed from multiple sclerosis cases. Although exposure to solvents is impossible to quantify, there appears to be a duration-dependent effect. Brain damage related to solvent abuse can begin within only a few years of the onset. In the context of substance abuse, the changes are relatively specific for solvent inhalation and do not appear to result from demyelination alone. Interaction with ethanol cannot be excluded as a compounding risk factor. PMID- 20300921 TI - [Meaningfullness and duration of palliative chemotherapy with regard to the quality of life of palliative patients]. AB - I am reporting on a 74-year-old female patient with primary pulmonary and hepatic metastatic colon cancer. In the course of three-and-a-half years the patient decided to receive multiple cycles of palliative chemotherapy, irradiation of the liver and of the upper body. As a result of the extended anti-tumour therapy, remissions of the advanced cancer disease could be achieved repeatedly, which lead to a substantial increase of the patient's quality of life. This case shows that even in an advanced palliative situation the goal of a multimodal treatment is to curb disease progression and to extend the life and increase quality of life of the patient. PMID- 20300922 TI - [Invasive tumor pain therapy in the final stage of a cervix cancer patient]. AB - Cancer disease is associated with a lot of very burdening symptoms. Pain is with dyspnea and emesis in the first time in a rate of about 50%, in the terminal stage up to 90% the most tormenting symptom. For more than 90% of patients the 3 step-WHO-regimen for cancer pain is able to relieve pain successfully. But a little group of cancer patients need invasive measures and methods to relieve pain sufficiently. This would be the 4th step, according to the enlarged WHO regimen. Intravenous or intrathecal applications, eventually regional blockades should be considered. The following case-report shows the steps of a difficult cancer pain therapy in a regional general hospital. It is sometimes not evidence based, on the one hand because of necessary organizational, staff-related, or other makeshifts in daily clinical practice, on the other hand because of the lack of appropriate EBM-guidelines. The pressure to reduce the pain effectively and as simple as possible produces sometimes polypragmatic, retrospective not always satisfying measures. PMID- 20300923 TI - [Radiotherapy of singular brain metastases]. AB - Single cerebral metastases in malignant disease pose a particular therapeutic challenge. The options consist of surgical resection, stereotactic radiation, and total brain irradiation. No significant therapeutic advantage for any of these methods has as yet been demonstrated in the literature. We present the case of a young patient with a single brain metastasis of a sigmoidal carcinoma, in stable general condition. We present our therapeutic regimen and discuss the various pros and cons of the different therapies. PMID- 20300924 TI - [Nutritional therapy in a rapid progressive course of malignant disease]. AB - On the basis of experience with a patient, the problems encountered in the inducement of a proper and timely nutritional therapy in the case of a rapidly advancing malignant disease are shown. The report addresses the issue of criteria for determining malnutrition as well as the difference between enteral nutrition and parenteral nutrition. PMID- 20300925 TI - ["Surgical intermediate care unit" outcomes, facts and experiences after 5 years]. AB - The increasing economic pressure has resulted in strategies to use efficient treatment forms. The aim of our study was to evaluate to which extent the intermediate care unit (IMC-unit) relieves the intensive care unit and the wards. We analyzed: patient population, age, gender, admission criteria and the rate of patients with intensive nursing procedures between January 1, 2005 and December 31, 2007. The level of care was calculated according to the standard patient categories. The mean age amounted to 58.9 years. Intensive care patients made up 43.6% and patients from the emergency ward 36.6% of the total IMC-allocation. After IMC care 54.3% of all IMC-patients could be taken over by wards. The confused patients amounted to 27.5% and isolated patients 4.3%. The average care intensity amounted to 4.5 hours per patient daily and the mean length of stay in hospital was 9 days. Particularly the relief of nursing intensity and the possibility of primary treatment of severely injured persons reflect the requirements of IMC. PMID- 20300926 TI - First described case of human granulocytic anaplasmosis in a patient in Eastern Austria. AB - A 64-year-old otherwise healthy patient presented with high fever, thrombocytopenia, elevated liver enzymes and an erythema on the belly. The patient remembered a tick bite four weeks ago when walking with his dog before the specific symptoms started. A meningococcal disease or hematological illness was excluded. The serological results for tick-borne diseases showed a high IgG antibody titer for Anaplasma phagocytophila. All symptoms and laboratory parameters normalized after one week of hospitalization. The patient received no treatment and recovered completely. This is the first confirmed case of human granulocytic anaplasmosis (HGA) in Eastern Austria. PMID- 20300928 TI - [Pelvic ring injuries in the elderly]. PMID- 20300927 TI - Tick-borne encephalitis in the age of general mobility. AB - The 11th meeting of the International Scientific Working Group on Tick-borne Encephalitis (ISW-TBE) was conducted under the title of, "From childhood to golden age: increased mobility - increased risk of contracting TBE?" Participants from 26 countries, including the United States of America and China, presented reports on the latest developments and trends in local TBE cases, vaccination coverage and risk factors. In particular, the situation of children and the elderly (the "golden agers") was discussed. As the current evidence suggests, the location and extension of endemic areas for TBE have changed over the last few years, along with global warming and the shift of infected ticks to higher altitudes. The increased mobility of the human population adds to the heightened exposure; outdoor activities and international travel are on the rise also, and especially, amongst the 50+ generation, who are already per se at higher risk of disease manifestation, complications and case fatality. Most Europeans travel within Europe, often without sufficient awareness of endemic areas. Only high immunization rates can ensure low disease rates in the long run. To achieve this goal, public education is the sole effective approach for raising the level of awareness. Overall, the risk of any given person to contract TBE should not be regarded as a fixed entity, but rather it must be estimated individually, on the basis of knowledge of the TBE virus endemic areas and risk factors. PMID- 20300929 TI - [Patellar fracture after patellar stabilization]. AB - We report on a 20-year-old female patient with a fracture of the patella after she fell on"black ice" 2 months after medial patellofemoral ligament (MPFL) reconstruction for patellar instability. For reconstruction of the MPFL, a single hamstring tendon graft was passed through the medial intermuscular septum and was fixed to the superomedial pole of the patella. The fracture was reduced by wire cerclage. Intraoperatively it was shown that the fracture line went through the patellar drill hole. No complications occurred during the further postoperative period. The literature contains only a few case reports describing fractures of the patella after MPFL reconstruction without any specific trauma. In this case, an interruption in blood supply with resulting avascular necrosis was suspected as a causal factor. PMID- 20300930 TI - Left hand, but not right hand, reaching is sensitive to visual context. AB - Recently, it has been reported that grasping with the left hand is more vulnerable to visual size illusions than grasping with the right hand. The present study investigated whether this increased sensitivity of the left hand for visual context extends to reaching. Left- and right-handed participants reached for targets embedded in two different visual contexts with either left or right hands. Visual context was manipulated by presenting targets either in a blank field or within an array of placeholders marking possible target locations. Regardless of handedness, the presence of placeholders affected left hand, but not right hand, reaching by improving end-point accuracy and reducing movement speed. Furthermore, left hand reaching was more accurate for far than near targets, whereas right hand reaching showed the opposite pattern. We discuss two possible hemispheric lateralization accounts of these findings. PMID- 20300931 TI - Somatotopic dominance in tactile temporal processing. AB - The sense of touch is initiated by stimulation of peripheral mechanoreceptors, and then the spatio-temporal pattern of the receptors' activation is interpreted by central cortical processing. To explore the tactile central processing, we psychophysically studied human judgments of the temporal relationships between two tactile events occurring at different skin locations. We examined four types of two-point temporal judgments-simultaneity, temporal order, apparent motion, and inter-stimulus interval-which differ from one another in time scale and task requirement. To perform any of the four temporal judgment tasks, the brain has to integrate spatially separated inputs. The main focus of the present study is to examine how the spatial separation affects the temporal judgment tasks. Two spatial coordinates can be defined in touch: the somatotopic coordinate, defined by cortical topography, and the spatiotopic coordinate, defined in the environment. In our experiments, the somatotopic distance was manipulated by stimulating the middle and index fingers of the same hand or different hands (ipsilateral vs. bilateral conditions), while the spatiotopic distance was manipulated by increasing the stimulators' separation under bilateral conditions (bilateral-near vs. bilateral-far conditions). Our results clearly demonstrated that all four of the temporal judgments were significantly affected by the somatotopic distance, but only slightly by the spatiotopic distance. The present results, together with the previous findings, suggest that tactile temporal judgments in a wide range of time scale, from several to several 100 ms, primarily reflect processing at the level of somatotopic representation unless the performance is further constrained by spatial processing. PMID- 20300932 TI - Widespread translocation from autosomes to sex chromosomes preserves genetic variability in an endangered lark. AB - Species that pass repeatedly through narrow population bottlenecks (<100 individuals) are likely to have lost a large proportion of their genetic variation. Having genotyped 92 Raso larks Alauda razae, a Critically Endangered single-island endemic whose world population in the Cape Verdes over the last 100 years has fluctuated between about 15 and 130 pairs, we found variation at 7 of 21 microsatellite loci that successfully amplified, the remaining loci being monomorphic. At 6 of the polymorphic loci variation was sex-linked, despite the fact that these microsatellites were not sex-linked in the other passerine birds where they were developed. Comparative analysis strongly suggests that material from several different autosomes has been recently transferred to the sex chromosomes in larks. Sex-linkage might plausibly allow some level of heterozygosity to be maintained, even in the face of persistently small population sizes. PMID- 20300933 TI - Association of inflammation of the left anterior descending coronary artery with cardiovascular risk factors, plaque burden and pericardial fat volume: a PET/CT study. AB - PURPOSE: Measurements of [(18)F]fluorodeoxyglucose (FDG) uptake as a potential marker of the inflammatory activity of the vessel wall could be useful to identify vulnerable atherosclerotic plaques. The purpose of this study was to correlate the FDG uptake in the left anterior descending coronary artery (LAD) with cardiovascular risk factors, pericardial fat volume (PFV) and calcified plaque burden (CPB). METHODS: A total of 292 consecutive tumour patients were examined by whole-body FDG PET and contrast-enhanced CT. The blood pool-corrected standardized uptake value (target to background ratio, TBR) was measured in the LAD, and the contrast-enhanced CT images were used to measure the PFV and the CPB. The Spearman correlation coefficient and the unpaired t test were used for statistical comparison between image-based results and cardiovascular risk factors. RESULTS: Vascular FDG uptake could be measured for 161 of 292 (55%) patients without myocardial uptake, but the vessel uptake could not be distinguished in the other patients, due to pervasive myocardial uptake. The TBR of the LAD showed significant correlations with hypertension (R = 0.18; p < 0.05), coronary heart disease (R = 0.19; p < 0.05), body mass index (BMI) (R = 0.19; p < 0.05), CPB (R = 0.36; p < 0.001) and PFV (R = 0.20; p < 0.05), but not with other risk factors. Patients with a TBR in the upper tertile had a larger CPB and a higher PFV than patients with a TBR in the lower tertile (9.1 vs 3.5; p < 0.001 for CPB and 92.2 vs 71.5 mm(3); p < 0.05 for PVF). CONCLUSION: FDG uptake measurement in the LAD correlates with hypertension, coronary heart disease, BMI, PFV and CPB. However, due to myocardial FDG uptake these measurements are only feasible in one half of the patients. PMID- 20300934 TI - Anticipating forest and range land development in central Oregon (USA) for landscape analysis, with an example application involving mule deer. AB - Forest policymakers, public lands managers, and scientists in the Pacific Northwest (USA) seek ways to evaluate the landscape-level effects of policies and management through the multidisciplinary development and application of spatially explicit methods and models. The Interagency Mapping and Analysis Project (IMAP) is an ongoing effort to generate landscape-wide vegetation data and models to evaluate the integrated effects of disturbances and management activities on natural resource conditions in Oregon and Washington (USA). In this initial analysis, we characterized the spatial distribution of forest and range land development in a four-county pilot study region in central Oregon. The empirical model describes the spatial distribution of buildings and new building construction as a function of population growth, existing development, topography, land-use zoning, and other factors. We used the model to create geographic information system maps of likely future development based on human population projections to inform complementary landscape analyses underway involving vegetation, habitat, and wildfire interactions. In an example application, we use the model and resulting maps to show the potential impacts of future forest and range land development on mule deer (Odocoileus hemionus) winter range. Results indicate significant development encroachment and habitat loss already in 2000 with development located along key migration routes and increasing through the projection period to 2040. The example application illustrates a simple way for policymakers and public lands managers to combine existing data and preliminary model outputs to begin to consider the potential effects of development on future landscape conditions. PMID- 20300935 TI - Effect of classification procedure on the performance of numerically defined ecological regions. AB - Ecological regionalizations define geographic regions exhibiting relative homogeneity in ecological (i.e., environmental and biotic) characteristics. Multivariate clustering methods have been used to define ecological regions based on subjectively chosen environmental variables. We developed and tested three procedures for defining ecological regions based on spatial modeling of a multivariate target pattern that is represented by compositional dissimilarities between locations (e.g., taxonomic dissimilarities). The procedures use a "training dataset" representing the target pattern and models this as a function of environmental variables. The model is then extrapolated to the entire domain of interest. Environmental data for our analysis were drawn from a 400 m grid covering all of Switzerland and consisted of 12 variables describing climate, topography and lithology. Our target patterns comprised land cover composition of each grid cell that was derived from interpretation of aerial photographs. For Regionalization 1 we used conventional cluster analysis of the environmental variables to define 60 hierarchically organized levels comprising from 5 to 300 regions. Regionalization 1 provided a base-case for comparison with the model based regionalizations. Regionalization 2, 3 and 4 also comprised 60 hierarchically organized levels and were derived by modeling land cover composition for 4000 randomly selected "training" cells. Regionalization 2 was based on cluster analysis of environmental variables that were transformed based on a Generalized Dissimilarity Model (GDM). Regionalization 3 and 4 were defined by clustering the training cells based on their land cover composition followed by predictive modeling of the distribution of the land cover clusters using Classification and Regression Tree (CART) and Random Forest (RF) models. Independent test data (i.e. not used to train the models) were used to test the discrimination of land cover composition at all hierarchical levels of the regionalizations using the classification strength (CS) statistic. CS for all the model-based regionalizations was significantly higher than for Regionalization 1. Regionalization 3 and 4 performed significantly better than Regionalization 2 at finer hierarchical levels (many regions) and Regionalization 4 performed significantly better than Regionalization 3 for coarse levels of detail (few regions). Compositional modeling can significantly increase the performance of numerically defined ecological regionalizations. CART and RF-based models appear to produce stronger regionalizations because discriminating variables are able to change at each hierarchic level. PMID- 20300936 TI - Spatial differentiation of landscape values in the Murray River region of Victoria, Australia. AB - This research advances the understanding of the location of perceived landscape values through a statistically based approach to spatial analysis of value densities. Survey data were obtained from a sample of people living in and using the Murray River region, Australia, where declining environmental quality prompted a reevaluation of its conservation status. When densities of 12 perceived landscape values were mapped using geographic information systems (GIS), valued places clustered along the entire river bank and in associated National/State Parks and reserves. While simple density mapping revealed high value densities in various locations, it did not indicate what density of a landscape value could be regarded as a statistically significant hotspot or distinguish whether overlapping areas of high density for different values indicate identical or adjacent locations. A spatial statistic Getis-Ord Gi* was used to indicate statistically significant spatial clusters of high value densities or "hotspots". Of 251 hotspots, 40% were for single non-use values, primarily spiritual, therapeutic or intrinsic. Four hotspots had 11 landscape values. Two, lacking economic value, were located in ecologically important river red gum forests and two, lacking wilderness value, were near the major towns of Echuca-Moama and Albury-Wodonga. Hotspots for eight values showed statistically significant associations with another value. There were high associations between learning and heritage values while economic and biological diversity values showed moderate associations with several other direct and indirect use values. This approach may improve confidence in the interpretation of spatial analysis of landscape values by enhancing understanding of value relationships. PMID- 20300937 TI - Four pathogenic Candida species differ in salt tolerance. AB - The virulence of Candida species depends on many environmental conditions, including extracellular pH and concentration of alkali metal cations. Tests of the tolerance/sensitivity of four pathogenic Candida species (C. albicans, C. dubliniensis, C. glabrata, and C. parapsilosis) to alkali metal cations under various growth conditions revealed significant differences among these species. Though all of them can be classified as rather osmotolerant yeast species, they exhibit different levels of tolerance to different salts. C. parapsilosis and C. albicans are the most salt-tolerant in general; C. dubliniensis is the least tolerant on rich YPD media and C. glabrata on acidic (pH 3.5) minimal YNB medium. C. dubliniensis is relatively salt-sensitive in spite of its ability to maintain as high intracellular K(+)/Na(+) ratio as its highly salt-tolerant relative C. albicans. On the other hand, C. parapsilosis can grow in the presence of very high external NaCl concentrations in spite of its high intracellular Na(+) concentrations (and thus lower K(+)/Na(+) ratio) and thus resembles salt-tolerant (halophilic) Debaryomyces hansenii. PMID- 20300938 TI - One novel homozygous mutation of SLC39A4 gene in a Chinese patient with acrodermatitis enteropathica. AB - Acrodermatitis enteropathica, a rare autosomal recessive disease, manifests as periorificial and symmetrical acral dermatitis, alopecia, and diarrhea due to insufficient zinc uptake by the intestine. Recent research revealed that mutations in the SLC39A4 gene are responsible for acrodermatitis enteropathica. This gene encodes one member of a human zinc transporter-like protein, also known as ZIP4. We detected one novel homozygous mutation c.1115T > G in the human SLC39A4 gene in one Chinese patient, which leading to p.L372R of the ZIP4. Homology analysis shows Leu372 in ZIP4 is conserved in Eutheria. PMID- 20300939 TI - Two new mutations of the ADAR1 gene associated with dyschromatosis symmetrica hereditaria. AB - Dyschromatosis symmetrica hereditaria (DSH) is a pigmentary genodermatosis of autosomal dominant inheritance characterized by a mixture of hyperpigmented and hypopigmented macules distributed on the dorsal aspects of the hands and feet. Genetic studies have identified mutations in ADAR1 gene to be responsible for this disorder. We detected two mutations in two families with DSH, which include a heterozygous g-->a transversion at the first base of the 3'-acceptor splice site of intron 5 (c. 2080-1g>a, IVS5-1g>a) and a transition c.3076C>T. IVS5-1g>a should prevent proper splicing of the transcript while c.3076C>T leading to a missense mutation p.R1026W of the ADAR1 gene. Our study suggests that splice site mutation IVS5-1g>a and missense mutation p.R1026W are new mutations of ADAR1 gene, which should be useful in genetic counseling and prenatal diagnosis for the affected families and expanding the database on ADAR1 gene mutations in DSH. PMID- 20300940 TI - Validation of adequate endogenous reference genes for the normalisation of qPCR gene expression data in human post mortem tissue. AB - Gene expression analyses based on messenger RNA (mRNA) profiling require accurate data normalisation. When using endogenous reference genes, these have to be validated carefully. Therefore, we examined the transcript stability of 10 potential reference genes using quantitative real-time polymerase chain reaction: beta actin, 18S rRNA, glyceraldehyde-3-phosphate dehydrogenase, TATA box-binding protein, hypoxanthine phosphoribosyl-transferase I, beta-2-microglobulin, hydroxymethylbilane synthase, succinate dehydrogenase complex, subunit A, cyclophilin A and ubiquitin C. The aim of the current study was to assess which reference genes show stable mRNA levels in human post mortem cardiac muscle, skeletal muscle and brain tissue. Considering cardiac muscle tissue, CYCA and TBP were identified as the most stable while in skeletal muscle tissue, SDHA and TBP, and in brain tissue, SDHA and HMBS turned out to be the most stable. Furthermore, we recommend a minimum of four carefully validated endogenous control genes for reliable data normalisation in human post mortem tissue. Parameters influencing the stability of transcript amounts were found to be mainly the post mortem interval in cardiac muscle and skeletal muscle tissue and the donor's cause of death in skeletal muscle and brain samples. Further parameters like gender, age at death and body mass index were found to influence mRNA quantities in skeletal muscle only. The set of stable control genes identified in this study may be used in further studies if the composition of the samples is similar to the one used here. PMID- 20300941 TI - Center-of-mass alterations and visual illusion of extent. AB - In the present communication, we have developed a computational model related to the conception of positional coding via centers-of-masses (centroids) of the objects' luminance distributions. The model predictions have been tested by the results of our psychophysical study of geometrical illusion of extent evoked by a modified Brentano figure consisting of three separate spots clusters. In experiments, the centroids of the clusters were manipulated by varying the positions of additional non-target spots flanking the stimulus terminators. A good correspondence between the model predictions and the illusion magnitude changes provided convincing evidences in favor of "centroid" explanation of origin of the illusion investigated. PMID- 20300942 TI - Simulated visual homing in desert ant natural environments: efficiency of skyline cues. AB - Desert ants, foraging in cluttered semiarid environments, are thought to be visually guided along individual, habitual routes. While other navigational mechanisms (e.g. path integration) are well studied, the question of how ants extract reliable visual features from a complex visual scene is still largely open. This paper explores the assumption that the upper outline of ground objects formed against the sky, i.e. the skyline, provides sufficient information for visual navigation. We constructed a virtual model of the ant's environment. In the virtual environment, panoramic images were recorded and adapted to the resolution of the desert ant's complex eye. From these images either a skyline code or a pixel-based intensity code were extracted. Further, two homing algorithms were implemented, a modified version of the average landmark vector (ALV) model (Lambrinos et al. Robot Auton Syst 30:39-64, 2000) and a gradient ascent method. Results show less spatial aliasing for skyline coding and best homing performance for ALV homing based on skyline codes. This supports the assumption of skyline coding in visual homing of desert ants and allows novel approaches to technical outdoor navigation. PMID- 20300943 TI - Keeping an eye on the violinist: motor experts show superior timing consistency in a visual perception task. AB - Common coding theory states that perception and action may reciprocally induce each other. Consequently, motor expertise should map onto perceptual consistency in specific tasks such as predicting the exact timing of a musical entry. To test this hypothesis, ten string musicians (motor experts), ten non-string musicians (visual experts), and ten non-musicians were asked to watch progressively occluded video recordings of a first violinist indicating entries to fellow members of a string quartet. Participants synchronised with the perceived timing of the musical entries. Results revealed significant effects of motor expertise on perception. Compared to visual experts and non-musicians, string players not only responded more accurately, but also with less timing variability. These findings provide evidence that motor experts' consistency in movement execution-a key characteristic of expert motor performance-is mirrored in lower variability in perceptual judgements, indicating close links between action competence and perception. PMID- 20300944 TI - The Sos-recruitment system as a tool to analyze cellular localization of plant proteins: membrane localization of Arabidopsis thaliana PEPINO/PASTICCINO2. AB - We have explored a modified cytosolic yeast-two-hybrid Sos-recruitment system (SRS) in order to test for membrane localization of a protein. In this system, membrane localization is assessed by rescue of a yeast strain carrying a temperature-sensitive mutation in the CDC25 gene (cdc25-2) at restrictive temperature. The homologous human Sos (hSos) is capable to replace cdc25-2 provided that it is attached to the membrane because only then hSos is functional. This can be achieved when hSos is artificially fused to a protein containing trans-membrane domains (Tms). GFP/YFP fusion construct analyses of the Arabidopsis thaliana PEPINO/PASTICCINO2 (PEP/PAS2) protein have previously shown disparate cellular localizations although this protein possesses clear Tms. Analysis of N-terminal and C-terminal hSos-PEP/PAS2 fusions respectively suggests, that PEP/PAS2 is an integral membrane protein with cytosolic N- and C termini. This implies that the protein has an even number of Tms and that the first Tm, a signal peptide, is not cleaved off. Our study shows that SRS is suitable to test for protein membrane localization and possibly for more detailed topological analysis of membrane proteins. PMID- 20300945 TI - Clinical usefulness of AGEs as a biomarker for the attenuation of NASH. PMID- 20300946 TI - A giant fusiform aneurysm of the external carotid artery branch in an infant. PMID- 20300947 TI - Detection of bone erosion in early rheumatoid arthritis: ultrasonography and conventional radiography versus non-contrast magnetic resonance imaging. AB - Nowadays, there is a trend toward early diagnosis and treatment of rheumatoid arthritis (RA) especially in patients with early signs of bone erosion which can be detected by magnetic resonance imaging (MRI). The aim of following study is to compare the sensitivity and specificity of ultrasonography (US) and conventional radiography (CR) compared to MRI for early detection of bone erosion in RA patients. In 12 patients with RA diagnosis, 120 first to fifth metacarpophalangeal joints and 96 second to fifth proximal interphalangeal joints were examined. Non-contrast MRI, US and CR were performed for bone erosion evaluation. For further analysis, the patients were divided in two equal groups according to disease activity score (DAS28). The overall sensitivity and specificity of US compared to MRI in detecting bone erosion were 0.63 and 0.98, respectively with a considerable agreement (kappa = 0.68, p < 0.001). Sensitivity and specificity of CR compared to MRI in detecting bone erosion were 0.13 and 1.00, respectively (kappa = 0.20, p < 0.001). In patients with more active disease, the sensitivity and specificity were 0.67 and 0.99 (kappa = 0.74, p < 0.001) compared to 0.59 and 0.97 (kappa = 0.61, p < 0.001) for the rest of patients according to DAS28. Conclusively, these findings reveal an acceptable agreement between US and MRI for detection of bone erosion in patients with early RA but not CR. US might be considered as a valuable tool for early detection of bone erosion especially when MRI is not available or affordable. Besides, it seems the US could be more reliable when the disease is more active. PMID- 20300948 TI - An evaluation of the usefulness of Staphylococcus aureus serodiagnosis in clinical practice. PMID- 20300949 TI - Eradication of the commensal intestinal microflora by oral antimicrobials interferes with the host response to lipopolysaccharide. AB - The host components and commensal microorganisms of the intestinal microenvironment play roles in the development and maintenance of the host defence. Recent observations have suggested that toll-like receptors (TLRs) are involved in the recognition of innate immunity against intestinal microbes. However, little is known regarding the role of TLR in the maintenance of systemic host defence by intestinal microorganisms. We studied the expression and function of TLR4 and TLR2 on alveolar and peritoneal macrophages in mice after 3 weeks of oral administration of streptomycin and cefotaxime. After active treatment, the intestinal microorganisms were nearly completely eradicated, and the surface expression of TLR4 and TLR2 on the peritoneal macrophages was prominently downregulated. When the actively treated mice were challenged with lipopolysaccharide (LPS), a TLR4 ligand, the host response was markedly impaired. Our results suggest that the oral administration of antimicrobials downregulates the expression of surface TLR on the peritoneal macrophages and modulates the host immune responses against LPS by modifying the intestinal environment. PMID- 20300950 TI - A model for arterial adaptation combining microstructural collagen remodeling and 3D tissue growth. AB - Long-term adaptation of soft tissues is realized through growth and remodeling (G&R). Mathematical models are powerful tools in testing hypotheses on G&R and supporting the design and interpretation of experiments. Most theoretical G&R studies concentrate on description of either growth or remodeling. Our model combines concepts of remodeling of collagen recruitment stretch and orientation suggested by other authors with a novel model of general 3D growth. We translate a growth-induced volume change into a change in shape due to the interaction of the growing tissue with its environment. Our G&R model is implemented in a finite element package in 3D, but applied to two rotationally symmetric cases, i.e., the adaptation towards the homeostatic state of the human aorta and the development of a fusiform aneurysm. Starting from a guessed non-homeostatic state, the model is able to reproduce a homeostatic state of an artery with realistic parameters. We investigate the sensitivity of this state to settings of initial parameters. In addition, we simulate G&R of a fusiform aneurysm, initiated by a localized degradation of the matrix of the healthy artery. The aneurysm stabilizes in size soon after the degradation stops. PMID- 20300951 TI - Aurora kinase A induces miR-17-92 cluster through regulation of E2F1 transcription factor. AB - Aurora kinase A (AURKA) is an essential mitotic serine/threonine kinase and its abnormal expression is observed in many malignancies, yet the exact role for AURKA in tumorigenesis still remains elusive. Here, through a transcription factor array, we show that the transcription activity of E2F1 was increased by AURKA overexpression. Meanwhile, the E2F1 protein level was found to be upregulated and a correlation between AURKA and E2F1 expression was observed in cancer specimens. Further analysis revealed that AURKA increased E2F1 protein stability by inhibiting proteasome-dependent degradation of this protein. Additionally, a microRNA cluster, miR-17-92, was found to be upregulated upon AURKA overexpression, and this stimulation was largely repressed by E2F1 knockdown. Chromatin immunoprecipitation further demonstrated that AURKA enhanced E2F1 occupancy to the promoter of the miR-17-92 cluster. These data reveal a novel link between AURKA and microRNAs via the regulation of E2F1, providing new clues for understanding the role of AURKA in tumorigenesis. PMID- 20300953 TI - Hydroxyapatite nanoparticles as a controlled-release carrier of BMP-2: absorption and release kinetics in vitro. AB - Recently, nanoparticles have been extensively developed as controlled-release carriers; however, there has been little research on hydroxyapatite nanoparticles (HANPs) and their potential applications. In this study, HANPs were investigated as a controlled-release carrier of bone morphogenetic protein-2 (BMP-2), the absorption and release kinetics of which were analyzed in vitro. Different concentrations of BMP-2 solution were used to evaluate the adsorptive properties of HANPs. It was observed that the amount of BMP-2 adsorbed onto HANPs could be as high as 70 mug/mg and that adsorption rate was highly correlated with the concentration of BMP-2 solution used. After absorption, the suspension of HANPs absorbed BMP-2 (HANPs/BMP-2) was incubated at 37 degrees C for 15 days and the release kinetics of BMP-2 from HANPs/BMP-2 was determined daily. The release profile showed sustained release of BMP-2 over the period of the investigation. Collectively, these results suggest that HANPs has the potential to function as a carrier for drug delivery systems and as a scaffold material in bone tissue engineering. PMID- 20300954 TI - In vivo study of ethyl-2-cyanoacrylate applied in direct contact with nerves regenerating in a novel nerve-guide. AB - Stitch suture is still the most recommended method to hold a nerve-guide in place but stitch suture is a well known cause of local inflammatory response. Glues of several kinds have been proposed as an alternative but they are not easy to apply in a real surgical setting. In 2006 authors developed a new concept of nerve guide termed "NeuroBox" which is double-halved, not-degradable and rigid, and allows the use of cyanoacrylic glues. In this study, Authors analyzed histologically the nerve-glue interface. Wistar rats were used as animal model. In group 1, animals were implanted a NeuroBox to promote the regeneration of an experimentally produced 4 mm gap in the sciatic nerve. In group 2, the gap was left without repair ("sham-operated" group). Group 3 was assembled by harvesting 10 contralateral intact nerves to document the normal anatomy. Semi-thin sections for visible light microscopy and ultra-thin sections for Transmission Electron Microscopy were analyzed. Results showed that application of ethyl-2 cyanoacrylate directly to the epineurium produced no significative insult to the underlining nerve fibers nor impaired nerve regeneration. No regeneration occurred in the "sham-operated" group. PMID- 20300952 TI - Centrioles: active players or passengers during mitosis? AB - Centrioles are cylinders made of nine microtubule (MT) triplets present in many eukaryotes. Early studies, where centrosomes were seen at the poles of the mitotic spindle led to their coining as "the organ for cell division". However, a variety of subsequent observational and functional studies showed that centrosomes might not always be essential for mitosis. Here we review the arguments in this debate. We describe the centriole structure and its distribution in the eukaryotic tree of life and clarify its role in the organization of the centrosome and cilia, with an historical perspective. An important aspect of the debate addressed in this review is how centrioles are inherited and the role of the spindle in this process. In particular, germline inheritance of centrosomes, such as their de novo formation in parthenogenetic species, poses many interesting questions. We finish by discussing the most likely functions of centrioles and laying out new research avenues. PMID- 20300955 TI - Raising the stakes: assessing the human service response to the advent of a casino. AB - This article reports the findings of one county's human service network's readiness to treat gambling related problems in anticipation of the opening of a new casino. Using a cross-sectional survey design, questionnaires were mailed to executive directors of all mental health, family counseling, drug and alcohol, and faith-based, addiction-related organizations in the county (N = 248); 137 (55.2%) agency directors responded to the questionnaire. The survey requested information about agency demographics, training, screening, treatment, and public awareness/education. Descriptive statistics and bivariate analyses were used to summarize the findings. The analyses revealed a lack of human service response to the impending start of casino gambling. More than three-quarters of respondents had not sent staff for training in screening or treating gambling disorders, did not screen for problem gambling, did not treat problem gambling, and did not refer clients to other agencies for treatment of gambling-related problems. The most common reason offered for not engaging in prevention and treatment activities was that problem gambling is not considered an issue for the agency. There were differences between mental health and/or substance abuse focused agencies and other service providers. Based on the findings of this study, specific strategies to enhance the service delivery network's capacity to address problem gambling are suggested. PMID- 20300956 TI - What do genetic counselors learn on the job? A qualitative assessment of professional development outcomes. AB - Professional development is an important goal for professionals in human service fields such as counseling, teaching, and nursing. However, there are relatively few published papers on this topic specific to genetic counselors, and no studies systematically examine the outcomes of their professional development. This study was designed to investigate genetic counselors' perceptions of their post-degree learning and to compare themes in their learning to those of psychotherapist professional development models. Two hundred ninety-three genetic counselors completed the demographics portion of an anonymous online survey, and of these, 185 also responded to at least one of two open-ended items: What is the most important thing you have learned about yourself in your practice as a genetic counselor? and What advice would you give to genetic counseling students just starting their career? An interpretative content-analysis method was used to extract three major themes: Intrapersonal lessons, Interpersonal lessons, and Professional lessons. Training and practice implications and research recommendations are provided. PMID- 20300957 TI - Morphologically accurate reduced order modeling of spiking neurons. AB - Accurately simulating neurons with realistic morphological structure and synaptic inputs requires the solution of large systems of nonlinear ordinary differential equations. We apply model reduction techniques to recover the complete nonlinear voltage dynamics of a neuron using a system of much lower dimension. Using a proper orthogonal decomposition, we build a reduced-order system from salient snapshots of the full system output, thus reducing the number of state variables. A discrete empirical interpolation method is then used to reduce the complexity of the nonlinear term to be proportional to the number of reduced variables. Together these two techniques allow for up to two orders of magnitude dimension reduction without sacrificing the spatially-distributed input structure, with an associated order of magnitude speed-up in simulation time. We demonstrate that both nonlinear spiking behavior and subthreshold response of realistic cells are accurately captured by these low-dimensional models. PMID- 20300958 TI - A Validation of Blanchard's typology: comment on Nuttbrock et al. (2010). PMID- 20300959 TI - Colchicine-induced apoptosis was prevented by glycogen synthase kinase-3 inhibitors in PC12 cells. AB - The purpose of this study was to examine whether glycogen synthase kinase-3 (GSK 3) is involved in colchicine-induced cell death in PC12 cells by using GSK inhibitors. Colchicine increased apoptotic cell death with morphological changes characterized by cell shrinkage and nuclear condensation or fragmentation. GSK-3 inhibitors such as alsterpaullone, SB216763, and AR-A014418 prevented colchicine induced cell death and caspase-3 activation. These results suggest that colchicine induces caspase-dependent apoptotic cell death and that GSK-3 activation is involved in cell death in PC12 cells. PMID- 20300960 TI - Predictors of interobserver agreement in breast imaging using the Breast Imaging Reporting and Data System. AB - The Breast Imaging Reporting and Data System (BI-RADS) was introduced in 1993 to standardize the interpretation of mammograms. Though many studies have assessed the validity of the system, fewer have examined its reliability. Our objective is to identify predictors of reliability as measured by the kappa statistic. We identified studies conducted between 1993 and 2009 which reported kappa values for interpreting mammograms using any edition of BI-RADS. Bivariate and multivariate multilevel analyses were used to examine associations between potential predictors and kappa values. We identified ten eligible studies, which yielded 88 kappa values for the analysis. Potential predictors of kappa included: whether or not the study included negative cases, whether single- or two-view mammograms were used, whether or not mammograms were digital versus screen-film, whether or not the fourth edition of BI-RADS was utilized, the BI-RADS category being evaluated, whether or not readers were trained, whether or not there was an overlap in readers' professional activities, the number of cases in the study and the country in which the study was conducted. Our best multivariate model identified training, use of two-view mammograms and BI-RADS categories (masses, calcifications, and final assessments) as predictors of kappa. Training, use of two-view mammograms and focusing on mass description may be useful in increasing reliability in mammogram interpretation. Calcification and final assessment descriptors are areas for potential improvement. These findings are important for implementing policies in BI-RADS use before introducing the system in different settings and improving current implementations. PMID- 20300962 TI - Present at the creation: the clinical pastoral movement and the origins of the dialogue between religion and psychiatry. AB - The contemporary dialogue between religion and psychiatry has its roots in what is called the clinical pastoral movement. The early leaders of the clinical pastoral movement (Anton Boisen, Elwood Worcester, Helen Flanders Dunbar, and Richard Cabot) were individuals of talent, even genius, whose lives and work intersected one another in the early decades of the twentieth century. Their legacy endures in the persons they inspired and continue to inspire and in the professional organizations and academic programs that profit from their pioneering work. To understand them and the era of their greatest productivity is to understand some of what psychiatry and religion have to say to each other. Appreciating their legacy requires attention to the context of historical movements and forces current in America at the end of the nineteenth and the beginning of the twentieth century that shaped religious, psychiatric, and cultural discourse. This essay attempts to provide an introduction to this rich and fascinating material. This material was first presented as a Grand Rounds lecture at The New York Presbyterian Hospital, Payne Whitney Westchester in the Department of Psychiatry, Weill Cornell Medical College. PMID- 20300963 TI - Cancer survivors' spiritual well-being and use of complementary methods: a report from the American Cancer Society's Studies of Cancer Survivors. AB - We examined associations between spiritual well-being and CAM use among 4,139 cancer survivors. We also explored the classification of religious/spiritual practices (R/S) as CAMs and alternative subscale structures of the Functional Assessment of Chronic Illness Therapy--Spiritual Well-being (FACIT-Sp). We evaluated three aspects of spirituality, Faith, Peace, and Meaning, and use of 19 CAMs in 5 domains. Mind-body methods were subdivided into R/S and non-R/S. All FACIT-Sp factors were associated with CAM use, but in different directions: Meaning and Faith were positively associated; Peace was negatively associated. Peace was negatively associated with R/S CAMs, but not non-R/S CAMs. The prevalence of CAM use dropped from 79.3 to 64.8% when R/S items were excluded. These findings confirm an association between spiritual well-being and CAM use, including some non-R/S CAMs, and provide evidence of the benefits of using the three-factor FACIT-Sp solution and treating R/S CAMs as a separate category. PMID- 20300964 TI - On defining "mental disorder": purposes and conditions of adequacy. AB - All definitions of mental disorder are backed up by arguments that rely on general criteria (e.g., that a definition should be consistent with ordinary language). These desiderata are rarely explicitly stated, and there has been no systematic discussion of how different definitions should be assessed. To arrive at a well-founded list of desiderata, we need to know the purpose of a definition. I argue that this purpose must be practical; it should, for example, help us determine who is entitled to publicly funded health care. I then propose eight conditions of adequacy that can be used to assess competing definitions (e.g., the ordinary language condition, the coherence condition, and the condition of normative adequacy). These conditions pull in different directions, however, and we must decide which are most important. I also suggest that there is no single definition that can help us deal with all the relevant practical issues. PMID- 20300965 TI - 2010 TNM staging system for cutaneous melanoma...and beyond. PMID- 20300966 TI - Sentinel node identification rate and nodal involvement in the EORTC 10981-22023 AMAROS trial. AB - BACKGROUND: The randomized EORTC 10981-22023 AMAROS trial investigates whether breast cancer patients with a tumor-positive sentinel node biopsy (SNB) are best treated with an axillary lymph node dissection (ALND) or axillary radiotherapy (ART). The aim of the current substudy was to evaluate the identification rate and the nodal involvement. METHODS: The first 2,000 patients participating in the AMAROS trial were evaluated. Associations between the identification rate and technical, patient-, and tumor-related factors were evaluated. The outcome of the SNB procedure and potential further nodal involvement was assessed. RESULTS: In 65 patients, the sentinel node could not be identified. As a result, the sentinel node identification rate was 97% (1,888 of 1,953). Variables affecting the success rate were age, pathological tumor size, histology, year of accrual, and method of detection. The SNB results of 65% of the patients (n = 1,220) were negative and the patients underwent no further axillary treatment. The SNB results were positive in 34% of the patients (n = 647), including macrometastases (n = 409, 63%), micrometastases (n = 161, 25%), and isolated tumor cells (n = 77, 12%). Further nodal involvement in patients with macrometastases, micrometastases, and isolated tumor cells undergoing an ALND was 41, 18, and 18%, respectively. CONCLUSIONS: With a 97% detection rate in this prospective international multicenter study, the SNB procedure is highly effective, especially when the combined method is used. Further nodal involvement in patients with micrometastases and isolated tumor cells in the sentinel node was similar-both were 18%. PMID- 20300967 TI - Ratio of metastatic to resected lymph nodes as a prognostic factor in node positive colorectal cancer. AB - BACKGROUND: This study was designed to assess the prognostic value of the ratio of metastatic to resected lymph nodes (lymph node ratio [LNR]) in patients with node-positive colorectal cancer (CRC). METHODS: From May 1998 to December 2007, data from a total of 514 patients who underwent curative surgery for CRC with proven lymph node metastases were analyzed. Patients were categorized into four groups on the basis of quartiles: LNR1 (<0.09), LNR2 (between 0.09 and 0.18), LNR3 (>0.18 and <0.34), and LNR4 (>=0.34). RESULTS: The median numbers of resected and metastatic nodes were 14 (range, 2-67) and 2 (range, 1-31), respectively. With a median follow-up period of 48.5 months, the 5-year overall survival rates of patients with LNR1, LNR2, LNR3, and LNR4 were 79, 72, 62, and 55%, respectively (P < 0.001); the 5-year disease-free survival rates of patients with LNR1, LNR2, LNR3, and LNR4 were 73, 67, 54, and 42%, respectively (P < 0.001). In the multivariate analysis, the LNR was an independent prognostic factor for both overall (P = 0.012) and disease-free survival (P = 0.009), as were pT and pN category. LNR remained statistically significant both in patients with <12 and with >12 nodes retrieved. CONCLUSIONS: In addition to the conventional pT and pN categories, the LNR was a predictor of both the overall and disease-free survival in patients with node-positive CRC. It may compensate for an inadequate lymph node dissection in surgery for CRC. PMID- 20300968 TI - A contemporary update on scleroderma. PMID- 20300969 TI - ADAM-17 over-expression in gallbladder carcinoma correlates with poor prognosis of patients. AB - The ADAMs is a multi-functional gene family of membrane proteins possessing a disintegrin and metalloprotease domain. They have potential implications for the metastasis of human tumor cells via cell adhesion and protease activities. However, no studies have yet comprehensively examined the expression of ADAMs in gallbladder carcinoma. The aim of this study was to test the hypothesis that ADAM 17 (otherwise known as tumor necrosis factor-alpha converting enzyme) is involved in the progression of gallbladder carcinoma. Two hundreds samples of gallbladder carcinoma and sixty non-cancerous gallbladder samples were used to measure the expression of total ADAM-17 by enzyme-linked immunosorbent assay, and the precursor and active forms by western blotting analysis. Expression of ADAM-17 was significantly increased in tumors with high histological grade and pT stage compared with low histological grade and pT stage tumors and was not associated with patients' gender, age, histological type, and resection margin involvement. Patients with high expression of ADAM-17 had a significantly shorter overall survival compared with those with low expression. Significantly, the prognostic impact of ADAM-17 was independent of conventional prognostic factors for gallbladder carcinoma. The current study demonstrated that the over-expression of ADAM-17 in patients with gallbladder carcinoma was linked closely with histological grade, pT stage and prognosis, and thus provides further impetus for exploiting ADAM-17 as new target for the treatment of gallbladder carcinoma. PMID- 20300970 TI - Painless acute pancreatitis associated with sorafenib treatment: a case report. AB - Sorafenib is a multikinase inhibitor that is used for the treatment of metastatic renal-cell carcinoma. We report the case of a patient with painless acute pancreatitis associated with sorafenib treatment. The patient was a 71-year-old man who had undergone surgery for left renal carcinoma and tumor thrombus in the inferior vena cava and right atrium (IVC-RA). After a follow-up period of 3 years, he developed right adrenal metastasis and received interferon (IFN)-alpha treatment. One year later, progression of the adrenal metastasis was observed, and he was admitted to a hospital for treatment with sorafenib, which was administered at a dose of 800 mg/day. Two weeks later, he developed painless acute pancreatitis associated with sorafenib treatment. Thereafter, sorafenib treatment was discontinued, and he was treated with conservative therapy. Three weeks later, he was discharged. Even though painless acute pancreatitis associated with sorafenib treatment is rare, the possible development of painless acute pancreatitis in patients undergoing sorafenib treatment must be kept in mind. PMID- 20300971 TI - The protective effects of intratympanic dexamethasone and vitamin E on cisplatin induced ototoxicity are demonstrated in rats. AB - Cisplatin ototoxicity is a major dose-limiting factor in the treatment of several neoplasms. Dexamethasone and vitamin E are two slow-acting free radical cleaners, and they have been shown to ameliorate nephrotoxicity and endothelial cell damage in animals receiving cisplatin. The purpose of the study was to determine the effectiveness of vitamin E and dexamethasone as an otoprotectant intratympanically. Prospective, randomized controlled trial in the rat model. Wistar rats were sedated using 50 mg/kg intraperitoneal ketamine and 7.5 mg/kg xylazine. Baseline auditory brainstem response (ABR) testing was performed in response to clicks and 4.8-, 12-, 16-kHz tone bursts. After auditory thresholds were determined, the animals received intraperitoneal drug administration according to one of the four groups. The rat groups received (group I) % 09 NaCl solution intratympanically (IT), (group II) cisplatin (20 mg/kg) only intraperitoneally (IP), (group III) dexamethasone (0.1-0.3 ml) IT and (group IV) vitamin E solution (0.1-0.3 ml) IT followed after 30 min by 20 mg/kg cisplatin. After the 3-day follow-up, ABR testing was performed and threshold changes were recorded. Group II animals showed marked hearing loss with average threshold shifts of 39.7 +/- 1.4 dB for clicks, 7.3 +/- 2.6 dB at 4 kHz, 8.4 +/- 1.6 dB at 8 kHz, 71.1 +/- 4.2 dB at 12 kHz and 71.9 +/- 5.9 dB at 16 kHz. No significant loss was observed in group III with shifts of 1.60 +/- 1.3 dB, 4.75 +/- 2.4 dB, 8.7 +/- 3.4 dB, and 4.3 +/- 2.1 dB for clicks and tone bursts at 4.8, 12, and 16 kHz, respectively. And similar findings were observed in group IV with shifts of 3.3 +/- 1.4 dB, 7.2 +/- 2.1 dB, 10.8 +/- 2 dB, and 13.3 +/- 3.1 dB for clicks and tone bursts at 4.8, 12, and 16 kHz, respectively. Significant protection was seen in group III and IV animals compared with group II animals. There is no side effect in IT administration of vitamin E and dexamethasone for hearing functions and two of them appear to have a easier, safer, usable protective effect against cisplatin ototoxicity. PMID- 20300972 TI - beta-Catenin overexpression in malignant glioma and its role in proliferation and apoptosis in glioblastma cells. AB - beta-Catenin, a core component of Wnt/beta-catenin signaling, has been shown to be a crucial factor in a broad range of tumors, while its role in glioma is not well understood. In this study, the expression of beta-catenin in astrocytic glioma tissues with different grade and human normal cerebral tissues was examined using reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry. We found a higher expression level of beta-catenin in astrocytic glioma patients with high grade in comparison with the normal controls. Additionally, siRNA was transfected into human U251 glioblastoma cells by liposome after the design of siRNA was confirmed to effectively inhibit the expression of beta-catenin by RT-PCR. Compared to the control siRNA group, siRNA mediated knockdown of beta-catenin in human U251 cells inhibited cell proliferation, resulted in cell apoptosis, and arrested cell cycle in G0/G1. Additionally, downregulation of beta-catenin decreased the expression level of cyclin D1, c-Myc and c-jun. Taken together, these results indicate that overexpression of beta-catenin may be an important contributing factor to glioma progression. PMID- 20300973 TI - Astrocyte-elevated gene-1 overexpression is associated with poor prognosis in gastric cancer. AB - Astrocyte-elevated gene-1 (AEG-1) plays an important role in diverse cancers and its up-regulation is associated with poor survival of patients. However, the status of AEG-1 expression and its significance in gastric cancer are still unclear. In this study, the expression of AEG-1 was studied in different gastric cancer cell lines and gastric cancer tissues. Expression of AEG-1 was significantly higher in gastric cancer tissues than that in normal tissues. Overexpression of AEG-1 was found in 62.9% of gastric cancers and significantly associated with TNM stage and Ki-67 proliferation index (P < 0.01). For survival study, overexpression of AEG-1 was significantly associated with poor survival (P < 0.01). Further multivariate analysis suggested that AEG-1 overexpression was an independent prognostic factor for the disease. We demonstrated that inhibition of AEG-1 expression by specific siRNA clearly inhibited SGC-7901 cell growth and enhanced cell apoptosis (P < 0.01). Inhibition of AEG-1 reduced phosphorylation of AKT and glycogen synthase kinase (GSK)-3beta (Ser 9) and decreased the level of beta-catenin, lymphoid enhancer binding factor 1 (LEF1), and Cyclin D1. This indicated that AEG-1 may play a role in Wnt/beta-catenin-mediated cancer progression. Taken together, overexpression of AEG-1 could be a useful prognostic factor in patients with gastric cancer. Targeted inhibition of AEG-1 may provide a novel therapeutic strategy for gastric cancer. PMID- 20300974 TI - Growth inhibitory effects of DJ-1-small interfering RNA on laryngeal carcinoma Hep-2 cells. AB - Cancer of the larynx is the commonest head and neck squamous cell carcinoma. The DJ-1 gene is a novel mitogen-dependent oncogene. Survivin is a structurally unique member of the inhibitors of apoptosis proteins. DJ-1 and survivin play important roles in carcinogenesis. The function of DJ-1, and the relationship between DJ-1 and survivin in laryngeal carcinoma, has never been explored. Small interfering RNAs (siRNAs) directed against the DJ-1 gene were initially transfected into laryngeal carcinoma Hep-2 cells with liposome. The viability of Hep-2 cells was then detected by the MTT assay. The changes in cell-cycle distribution were monitored by flow cytometry. Finally, changes in DJ-1 and survivin genes mRNA and protein levels were evaluated by semi-quantitative RT-PCR and Western blotting, respectively. Blocking expression of the DJ-1 gene with DJ 1-siRNA significantly suppressed the viability of Hep-2 cells. Treatment with DJ 1-siRNA resulted in a G2/M accumulation. Expressions of DJ-1 and survivin gene mRNA and protein levels were suppressed by DJ-1-siRNA in a dose-dependent manner. These data indicate, for the first time, that the DJ-1 gene may have an important role in the carcinogenesis of laryngeal carcinoma. PMID- 20300975 TI - The invasive malignancy from peritoneal epithelial cell: a report of four cases and review of literature. AB - To analyze the clinical characteristics, diagnosis and treatment of primary peritoneal carcinoma (PPC) and to review the literature, so as to raise the awareness of the disease. Four cases of PPC diagnosed in our department from March 2005 to September 2007 were retrospectively analyzed. Four cases were all treated with platinum-based chemotherapy. They were treated with intraperitoneal chemohyperthermia (IPCH) with cisplatin, carboplatin or oxaliplatin with a closed sterile circuit of 1,000 ml physiologic saline and inflow temperature is 43 degrees C, while they were receiving high-intensity focused microwave hyperthermia (HIFMH) concomitantly. Intravenous paclitaxel or docetaxel was used in three patients, while cyclophosphamide and adriamycin injection in another patient. After two cycles of chemotherapy, ascites decreased significantly or even disappeared. Up to 6 January 2010, the four cases had survived for 38, 51, 33 and 29 months, respectively. PPC is a group of invasive malignancy derived from the peritoneal epithelium, it is common in women and is homogeneous with ovarian cancer in pathology. Diagnosis relies mainly on postoperative pathologic diagnosis and cytology after ruling out ovarian cancer and gastrointestinal cancer. Platinum-containing chemotherapy, IPCH and the administration of taxanes can improve the overall response rate and long-term survival. PMID- 20300976 TI - Rho kinase inhibitor fasudil suppresses migration and invasion though down regulating the expression of VEGF in lung cancer cell line A549. AB - Rho and Rho-associated kinase play an important role in focal adhesion, stress fiber formation and cell motility. Fasudil is a kind of Rho kinase inhibitor. The effect and precise molecular mechanism of fasudil on the biology behavior of lung cancer cell A549 remains unclear. The cytotoxic effect of fasudil on A549 cell was measured by 3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Wound-healing assay was used to evaluate the effect of fasudil on migration activity of A549 cells. The invasion activity of A549 cells was detected by transwell chamber assay. The expression of MMPs was measured by gelatin zymography. RT-PCR and western blot were used to investigate the molecular change of A549 cells after treated with fasudil. Fasudil-inhibited proliferation of A549 cells in a concentration-dependent manner, decreased the migration and invasion activity. After treated with fasudil, the expression of MMP-2 and MMP-9 was significantly inhibited compared with the control group. Furthermore, the expression of RhoA and VEGF of A549 cell treated with fasudil was significantly down-regulated. Our findings indicate that fasudil might have a therapeutic potential for lung cancer though inhibiting cell proliferation, migration, invasion, MMPs activity and down-regulating the expression of RhoA and VEGF. PMID- 20300977 TI - Pathobiologic implications of methylation and expression status of Runx3 and CHFR genes in gastric cancer. AB - Runx3 and CHFR genes were defined as tumor suppressor genes in gastric cancer (GC) recently. This paper was to investigate the roles of methylation and expression status of Runx3 and CHFR genes in GC patients. Methylation-specific polymerase chain reaction (MSP) and bisulfite DNA sequencing (BSP) were used to detect methylation status of Runx3 and CHFR genes in GC patients. The expression of Runx3 and CHFR in GC patients was analyzed by reverse transcription polymerase chain reaction (RT-PCR) and immunohistochemical analysis. The expression of the protein and mRNA decreased remarkably in the patients with aberrant promoter methylation of Runx3 and CHFR genes. The methylation status of Runx3 and CHFR were inversely related to the tumor size, tumor invasion depth and tumor differentiation in GC patients. Moreover, the protein expression of Runx3 and CHFR were significantly correlated with tumor invasion depth and tumor differentiation, respectively. Aberrant promoter methylation of Runx3 and CHFR genes may be involved in the carcinogenesis and development of GC and may provide useful clues for the prediction of the malignant behaviors of GC. PMID- 20300978 TI - Gemcitabine and cisplatin in patients with carcinoma of unknown primary site. AB - The optimal therapy for carcinoma of unknown primary site (CUPS) is still under investigation. In this retrospective trial, we reported the response rates and overall and progression free survival of 23 CUPS patients that were treated with gemcitabine and cisplatin. The mean age of the patients was 54.95 (32-77). Sixteen (69.6%) of them were males and 7(30.4%) females. Totally 109 cycles with a mean of 6 were administered. Thirteen of 23 patients (56.5%) presented with only one metastatic site, and the liver is the most frequent metastatic site (39.1%). Histologic types were adenocarcinoma in 14 patients (60.8%), squamous carcinoma in 1 patient (4.8%), epithelioid cancer in 3 patients (13%) and undifferentiated cancer in 5 patients (21.7%). Three patient achieved a CR (13%), 4 patients achieved a PR (17.4%) and 8 patients had SD (34.8%) with an overall 30.4% response rate. However, 8 patients had progressive disease with a percentage of 34.8%. The median follow-up time was 10 months (3-42 months). The mean and median survival was 12.5 (3-42) months and 10 months (range, 3-42 months) and progression free survival was 5.5 months (range, 0-23 months). Gemcitabine plus cisplatin may be an effective treatment of CUPS. Therefore additional trials are needed especially with new chemotherapeutics. PMID- 20300979 TI - Expression of indoleamine 2,3-dioxygenase in acute myeloid leukemia and the effect of its inhibition on cultured leukemia blast cells. AB - Indoleamine 2,3-dioxygenase (IDO), a catabolizing enzyme of tryptophan, is a novel immunosuppressive agent blocking T-cell activation in neoplastic cells, including acute myeloid leukemia (AML) cells. IDO inhibitors as 1-methyl tryptophan (1MT) can abrogate IDO enzymatic activity and may result in an effective immune response. Mononuclear cells (MNCs) were separated from peripheral blood of 25 AML patients and 25 normal adults. IDO expression was detected by RT-PCR and its enzymatic activity by a colorimetric method. MNCs were cultured and the effects of Adriamycin, 1MT and a mixture of both on blast and lymphocyte cell counts after 24 and 72 h were detected. IDO mRNA and activity were detected in 52% of patients and absent in normal subjects. There was a significant correlation between IDO mRNA expression and its enzymatic activity in AML. IDO activity was correlated positively with patient's ages and negatively with hemoglobin levels. There was a significant inhibition of blast cells proliferation with Adriamycin and more inhibition when combined with 1MT. The inhibition was more after 72 h more than 24 h of culture. However, using 1MT alone showed no significant inhibitory effect on blast cells, with a significant increase in lymphocyte counts. Our study confirms the role of indoleamine 2,3 dioxygenase in tumor-induced immune tolerance and points to the possible benefit of 1-methyl tryptophan as immunotherapeutic enhancing the anticancer effects of traditional chemotherapeutics. PMID- 20300980 TI - Clinical significance of the ratio between the alpha 2 plasmin inhibitor-plasmin complex and the thrombin-antithrombin complex in advanced non-small cell lung cancer. AB - The aims of this study are to: (a) confirm the prognostic significance of the procoagulant molecules D dimer, thrombin-antithrombin complex (TAT), and plasmin alpha2-plasmin inhibitor complex (PIC); (b) to evaluate hemostatic activation in patients with advanced non-small cell lung cancer (NSCLC); and (c) to delineate the relationships between markers of hemostasis and other clinical characteristics. In this study, a low PIC/TAT ratio and poor PS were significant independent negative prognostic factors for survival in patients with advanced NSCLC. The PIC/TAT ratio may become a surrogate marker for treatment with anticoagulants in the future. PMID- 20300981 TI - Activated protein C resistance in the Japanese population due to homozygosity for the factor V R2 haplotype. PMID- 20300982 TI - Separation of antileukemic effects from graft-versus-host disease in MHC haploidentical murine bone marrow transplantation: participation of host immune cells. AB - Allogeneic hematopoietic stem cell transplantation (HSCT) is associated with both graft-versus-host disease (GVHD) and graft-versus-leukemia (GVL) effects. In clinical studies of HLA-mismatched HSCT, strong GVL effects have been reported. In the present study, we addressed the mechanism of the GVL and GVH response using MHC-haploidentical murine bone marrow transplantation (BMT) models. Recipient BDF1 (H-2(b/d)) mice received T cell-depleted bone marrow and spleen cells from B6C3F1 (H-2(b/k)) or C57BL/6 (H-2(b)) mice with or without P815 mastocytoma cells (H-2(d)) after receiving lethal total body irradiation. B6C3F1 -> BDF1 (hetero-to-hetero type) recipients showed more powerful antileukemic effects with less severe GVHD than C57BL/6 --> BDF1 (parent-to-F1 type) recipients. Compared with C57BL/6 --> BDF1 recipients, significantly higher in vitro cytotoxic activity against P815 cells was observed in B6C3F1 --> BDF1 recipients. Significantly lower CXCR3 expression on donor T cells and higher interferon (IFN)-gamma expression were considered to be associated with strong antileukemic effects with less severe GVHD in B6C3F1 --> BDF1 recipients. Furthermore, host immune cells, especially natural killer cells and CD8(+) T cells, were found to contribute remarkably to high IFN-gamma production in B6C3F1 --> BDF1 recipients. Thus, in MHC-haploidentical HSCT, host immune cells may change the balance between GVH and GVL response through IFN-gamma production. PMID- 20300984 TI - The prevalence of fentanyl in drug-related deaths in Philadelphia 2004-2006. AB - Fentanyl is an increasingly common drug of abuse. The Philadelphia Medical Examiner's Office reported 252 drug-related deaths in Philadelphia that tested positive for fentanyl during the year 2006 in comparison to 22 and 19 in 2005 and 2004, respectively. We reviewed the data from 2004 to 2006 from the Philadelphia Medical Examiner's office. Key words such as fentanyl, drug, cocaine, ethanol, medic (medication), tox (intoxication), or poison were used as search words. In comparison to 2004 and 2005 data, there was a statistically significant increase in number of drug-related deaths (DRDs) and the percentage of DRDs that tested positive for fentanyl in 2006. We postulate that the increase in DRDs in 2006 may be related to increase use or abuse of fentanyl, lack of general public awareness that fentanyl is a potent opioid, inadequate dose of naloxone and/or the surge of clandestinely manufactured fentanyl. PMID- 20300983 TI - Plasma levels of Hsp70 and anti-Hsp70 antibody predict risk of acute coronary syndrome. AB - Although immune reactions against heat shock proteins have been implicated in the pathogenesis of atherosclerosis, conflicting associations between Hsp70, anti Hsp70 antibody and coronary heart disease (CHD) have been reported. This study assessed whether there is a significant association between extracellular human Hsp70, anti-Hsp70 antibody and acute coronary syndrome (ACS) and stable angina (SA), and examined dynamic changes in Hsp70 and anti-Hsp70 antibody levels induced by acute myocardial infarction (AMI). Plasma Hsp70 and anti-Hsp70 antibody levels in 291 patients with ACS (179 AMI, 112 unstable angina), 126 patients with SA and 417 age and sex-matched healthy subjects, and in 40 patients after admission for AMI, and on day 2, 3, and 7 after the onset of AMI were determined using enzyme-linked immunosorbent assays. Hsp70 levels were significantly higher in ACS and SA and anti-Hsp70 antibody levels were only markedly lower in ACS than controls. After adjustment for traditional CHD risk factors, increasing levels of Hsp70 were significantly associated with an increased risk and severity of ACS (P for trend < 0.001), whereas increasing levels of anti-Hsp70 antibody were associated with a decreased risk of ACS (P for trend = 0.0003). High levels of Hsp70 combined with low levels of anti-Hsp70 antibody had a joint effect on the risk of ACS (OR, 5.14, 95% CI, 3.00-8.79; P < 0.0001). In patients with AMI, Hsp70 levels decreased rapidly from days 1-7 after onset, whereas anti-Hsp70 antibody levels increased in patients with AMI. These findings suggest that higher Hsp70 levels or lower anti-Hsp70 antibody levels are independently associated with a higher risk of ACS. Higher Hsp70 levels and lower anti-Hsp70 antibody levels combine to further increase this risk. PMID- 20300985 TI - Hypothermia and Fever after organophosphorus poisoning in humans--a prospective case series. AB - There have been many animal studies on the effects of organophosphorus pesticide (OP) poisoning on thermoregulation with inconsistent results. There have been no prospective human studies. Our aim was to document the changes in body temperature with OP poisoning. A prospective study was conducted in a rural hospital in Polonnaruwa, Sri Lanka. We collected data on sequential patients with OP poisoning and analyzed 12 patients selected from 53 presentations who had overt signs and symptoms of OP poisoning and who had not received atropine prior to arrival. All patients subsequently received specific management with atropine and/or pralidoxime and general supportive care. Tympanic temperature, ambient temperature, heart rate, and clinical examination and interventions were recorded prospectively throughout their hospitalization. Initial hypothermia as low as 32 degrees C was observed in untreated patients. Tympanic temperature increased over time from an early hypothermia (<35 degrees C in 6/12 patients) to later fever (7/12 patients >38 degrees C at some later point). While some of the late high temperatures occurred in the setting of marked tachycardia, it was also apparent that in some cases fever was not accompanied by tachycardia, making excessive atropine or severe infection an unlikely explanation for all the fevers. In humans, OP poisoning causes an initial hypothermia, and this is followed by a period of normal to high body temperature. Atropine and respiratory complications may contribute to fever but do not account for all cases. PMID- 20300986 TI - Investigation of source position uncertainties & balloon deformation in MammoSite brachytherapy on treatment effectiveness. AB - The MammoSite breast high dose rate brachytherapy is used in treatment of early stage breast cancer. The tumour bed volume is irradiated with high dose per fraction in a relatively small number of fractions. Uncertainties in the source positioning and MammoSite balloon deformation will alter the prescribed dose within the treated volume. They may also expose the normal tissues in balloon proximity to excessive dose. The purpose of this work is to explore the impact of these two uncertainties on the MammoSite dose distribution in the breast using dose volume histograms and Monte Carlo simulations. The Lyman-Kutcher and relative seriality models were employed to estimate the normal tissues complications associated with the MammoSite dose distributions. The tumour control probability was calculated using the Poisson model. This study gives low probabilities for developing heart and lung complications. The probability of complications of the skin and normal breast tissues depends on the location of the source inside the balloon and the volume receiving high dose. Incorrect source position and balloon deformation had significant effect on the prescribed dose within the treated volume. A 4 mm balloon deformation resulted in reduction of the tumour control probability by 24%. Monte Carlo calculations using EGSnrc showed that a deviation of the source by 1 mm caused approximately 7% dose reduction in the treated target volume at 1 cm from the balloon surface. In conclusion, accurate positioning of the (192)Ir source at the balloon centre and minimal balloon deformation are critical for proper dose delivery with the MammoSite brachytherapy applicator. On the basis of this study, we suggest that the MammoSite treatment protocols should allow for a balloon deformation of < or = 2 mm and a maximum source deviation of < or = 1 mm. PMID- 20300987 TI - Single cell RT-PCR on mouse embryos: a general approach for developmental biology. AB - Preimplantation development is a complicated process, which involves many genes. We have investigated the expression patterns of 17 developmentally important genes and isoforms in early mouse embryos as well as in single cells of the mouse embryo. The comparison is an excellent example for showing the importance of studying heterogeneity among cell populations on the RNA level, which is being increasingly addressed in basic research and medical sciences, particularly with a link to diagnostics (e.g. the analysis of circulating tumor cells and their progenitors). The ubiquitously expressed histone variant H3f3a and the transcription factor Pou5f1 generated mRNA-derived products in all analyzed preimplantation embryos (up to the morula stage) and in all analyzed blastomeres from 16-cell embryos, indicating a rather uniform reactivation of pluripotency gene expression during mouse preimplantation development. In contrast, genes that have been implicated in epigenetic genome reprogramming, such as DNA methyltransferases, methylcytosine-binding proteins, or base excision repair genes revealed considerable variation between individual cells from the same embryo and even higher variability between cells from different embryos. We conclude that at a given point of time, the transcriptome encoding the reprogramming machinery and, by extrapolation, genome reprogramming differs between blastomeres. It is tempting to speculate that cells expressing the reprogramming machinery have a higher developmental potential. PMID- 20300988 TI - Poly(A) cDNA real-time PCR for indicator gene measurement in cancer. AB - Microarray gene expression profiling has identified gene signatures or "Indicator" genes predictive of outcome in many cancer types including lymphoma, and more recently pancreatic cancer. This has identified novel and powerful diagnostic and prognostic and generically applicable markers, promising more specific diagnosis and treatment, together with improved understanding of pathobiology. There is now an urgent need to translate these signatures to clinical use. However, gene microarrays rely on relatively large amounts of fresh starting tissue obviating measurement of Indicator genes in routine practice, and there is a need for development of another, simple, robust, relatively inexpensive and sensitive method for their translation to clinical use. We have piloted the use of real-time PCR measurement of specific prognostic genes, so called "Indicator" genes, in globally amplified polyA cDNA for this purpose. Poly(A) PCR coordinately amplifies cDNA copies of all polyadenylated mRNAs, thereby generating a PCR product (polyA cDNA) whose composition reflects the relative abundance of all expressed genes in the starting sample. Poly(A) PCR enables global mRNA amplification from picogram amounts of RNA and has been routinely used to analyse expression in small samples including single cells. The poly(A) cDNA pool generated is also indefinitely renewable and as such represents a "molecular block". Real-time PCR measurement, using gene-specific primers and probes, of the expression levels of specific Indicator genes then allows gene signatures to be detected within the poly(A) cDNA, thereby enabling expression profiling of very small amounts of starting material. This chapter details this method as applied to fresh and paraffin embedded tissue and to pancreatic juice. In this chapter, we have concentrated on application of the method to pancreatic cancer, but the generic nature of the method renders it applicable to any cancer type, thereby representing a novel platform for cancer diagnosis across all tumour types. PMID- 20300989 TI - Transcriptome profiling of host-microbe interactions by differential display RT PCR. AB - In recent years, DNA microarray has become increasingly popular as a tool to investigate global expression patterns compared to differential display RT-PCR. Although differential display RT-PCR can be labour-intensive, it has its own merits over those of DNA microarray. While the latter usually consists of a well defined set of species-specific genes, differential display RT-PCR allows the investigation of host-microbe interactions without bias towards any mRNA transcripts. This means that the regulated transcript expression of both host and pathogen can be analysed simultaneously. In addition, novel transcripts and alternate splicing variants pertaining to the infection can also be discovered. We have investigated the response of rhabdomyosarcoma cells to infection with a neurovirulent strain of enterovirus 71 (EV71) at different time-points during the infection process compared with uninfected cells. Using differential display RT PCR, we identified mRNAs that were up- or down-regulated. Less than half of the clones match known genes including those involved in mediating the cytoskeleton, cell cycle, cell death, protein translational machinery and cellular transport. The rest of the clones do not match any known genes, of which several are novel genes. Noteworthy is the discovery of an alternate splicing form of TRIP7, which is down-regulated during EV71 infection. The differential display technique has potentially wide applicability to elucidate the gene expression or transcriptomic profiles of host-microbe interactions, which can provide a better understanding of microbial pathogenesis. PMID- 20300990 TI - Quantitative RT-PCR methods for mature microRNA expression analysis. AB - This chapter describes two methods to measure expression of mature miRNA levels using qRT-PCR. The first method uses stem-loop RT primers to produce cDNA for specific miRNAs, a technique that our laboratory has modified to increase the number of miRNAs being reverse transcribed within a single RT reaction from one (as suggested by the manufacturer) to five. The second method uses a modified oligo(dT) technique to reverse transcribe all transcripts within an RNA sample; therefore, target miRNA and normalizing mRNA can be analyzed from the same RT reaction. We examined the level of miRNA-132, a miRNA known to be upregulated in granulosa cells following hCG treatment, using both of these methods. Data were normalized to GAPDH or snU6 and evaluated by DeltaDeltaCt and standard curve analysis. There was no significant difference (P > 0.05) in miRNA-132 expression between the stem-loop and modified oligo(dT) RT methods indicating that both are statistically equivalent. However, from a technical point of view, the modified oligo(dT) method was less time consuming and required only a single RT reaction to reverse transcribe both miRNA and mRNA. PMID- 20300992 TI - Detection and identification of CD46 splicing isoforms by nested RT-PCR. AB - CD46 (Membrane Cofactor Protein, MCP) is a transmembrane glycoprotein, which is expressed by all nucleated human cells whose purpose is to protect against autologous complement attack. In addition, CD46 can serve as a receptor for several viruses and bacteria and as a potent regulator of the inflammatory response by affecting T cell differentiation. Multiple isoforms of CD46 exist due to alternative splicing and are coexpressed in human cells in various patterns and expression levels. However, specific diseases have not been associated with isoform coexpression. We applied a nested RT-PCR method to investigate the coexpression pattern of CD46 splicing variants in otosclerotic and normal stapes footplate specimens. Using this method, we detected an altered isoform expression pattern and identified four novel CD46 splicing variants overexpressed in otosclerotic bone. This study is the first comprehensive report to provide evidence for disease associated alternative splicing of CD46. PMID- 20300991 TI - Detection of influenza A virus neuraminidase and PB2 gene segments by one step reverse transcription polymerase chain reaction. AB - We describe a single step reverse transcription polymerase chain reaction protocol that can be used to amplify part of the neuraminidase gene segment (segment 6) from all nine subtypes of influenza A virus. The method has also been applied to amplify gene segment 1 of influenza A, which encodes the basic polymerase protein 2 (PB2). The method combines the use of mixed base primers with a "touchdown" thermal cycling program and is applicable to a wide range of nucleic acid targets in which there is genetic variability in the regions complementary to the PCR primers. PMID- 20300993 TI - Simultaneous detection of bluetongue virus RNA, internal control GAPDH mRNA, and external control synthetic RNA by multiplex real-time PCR. AB - Bluetongue is an insect-borne disease of domestic and wild ruminants that requires strict monitoring by sensitive, reproducible and robust methods. Real time reverse transcription polymerase chain reaction (RT-qPCR) analysis has become the method of choice for routine viral diagnosis. As false-negative test results can have serious implications; an internal/external control system should be incorporated in each analysis to detect RT-qPCR failure due to poor sample quality, improper nucleic acid extraction and/or PCR inhibition. To increase the diagnostic capacity and reduce costs, it is recommended to use a multiplex strategy which enables the amplification of multiple targets in a single reaction. This chapter describes the application of a triplex RT-qPCR for the simultaneous detection of bluetongue viral RNA, an internal control and an external control. The primer and probe sequences of the BTV RT-qPCR were taken from Toussaint et al. (J Virol Methods 140:115-123, 2007), whereas the internal and external RT-qPCRs were specifically designed to detect endogenous glyceraldehyde-3-phosphate dehydrogenase mRNA and a synthetic RNA, respectively. To maximize the sensitivity of the assay, the primer concentrations of the internal/external control reactions were limited and the amount of Taq DNA polymerase was increased. A comparison of the singleplex versus triplex RT-qPCR indicated that the triplex RT-qPCR exhibits a higher analytical sensitivity. Due to the incorporation of the internal/external control system, the triplex RT-qPCR allows an even more reliable and rapid diagnosis of bluetongue than the previously described singleplex RT-qPCR (J Virol Methods 140:115-123, 2007). PMID- 20300994 TI - Detection of West Nile viral RNA from field-collected mosquitoes in tropical regions by conventional and real-time RT-PCR. AB - West Nile virus (WNV) is an emerging mosquito-borne flavivirus, which has rapidly spread and is currently widely distributed. Therefore, efforts for WNV early detection and ecological surveillance of this disease agent have been increased around the world. Although virus isolation is known to be the standard method for detection and identification of viruses, the use of RT-PCR assays as routine laboratory tests provides a rapid alterative suitable for the detection of viral RNA on field-collected samples. A method for WNV RNA genome detection in field collected mosquitoes is presented in this chapter. This method has been designed for virus surveillance in tropical regions endemic for other flaviviruses. Reverse Transcriptase-PCR (RT-PCR) assays, both standard and real time, to detect WNV and other flaviviruses are described. A first screening for flavivirus RNA detection is performed using a conventional RT-PCR with two different sets of flavivirus consensus primers. Mosquito samples are then tested for WNV RNA by a real-time (TaqMan) RT-PCR assay. Sample preparation and RNA extraction procedures are also described. PMID- 20300995 TI - Detection of antisense RNA transcripts by strand-specific RT-PCR. AB - Comprehensive genome annotation requires extensive cDNA analysis. This analysis has identified natural antisense transcripts (NATs), which are distinct from the microRNAs, siRNAs, and piRNAs, in a number of diverse eukaryotes. This wide conservation supports the possibility of an important role for NATs in regulating cellular processes. Investigating their roles requires the confirmation of expressed sequence tag (EST) data and the detection of antisense transcripts in distinct cellular backgrounds. This chapter describes the use of a reverse transcription polymerase chain reaction (RT-PCR) method for the detection of antisense transcripts. The protocol was designed to reduce the number of first strand synthesis reactions during screening for antisense transcripts through the utilization of antisense directed primers and oligo dT to prime first strand synthesis. These results are further confirmed using sense and antisense directed primers in first strand synthesis. Results indicate that optimization of the screens requires proper controls to confirm removal of gDNA contamination and to rule out self-priming as a source of first strand products. PMID- 20300996 TI - RT-PCR amplification and cloning of large viral sequences. AB - A long reverse transcription polymerase chain reaction (LRP) protocol is described for the amplification of large RNA sequences. The amplification of near full-length hepatitis C virus (HCV) genome from serum samples is used as an example to detail each step in LRP procedure, including primer design, RNA extraction, reverse transcription, and PCR. The protocol for efficient cloning of such large amplicons is also presented. Since HCV represents a difficult template in terms of its near full-length amplification due to extensive secondary structures and low titers in clinical samples, methods described in this chapter should be applicable for other RNA viruses and cellular RNA templates. PMID- 20300997 TI - One-step RT-LATE-PCR for mRNA and viral RNA detection and quantification. AB - LATE-PCR is an optimized form of asymmetric PCR that efficiently generates high levels of single-stranded DNA amplicons. Single-stranded amplicons are advantageous because, as shown in this chapter, they can be probed at low temperature(s) with one or more probes. Based on its properties, LATE-PCR is also useful for constructing multiplex assays. Viral RNA or RNA present in cells can be detected and quantified using LATE-PCR preceded by a reverse transcription (RT) step that converts RNA into cDNA. According to the conventional two-step approach, RT is primed using nonspecific random oligonucleotides prior to performing PCR amplification in a separate step. Recently, however, the so-called "one-step" RT-PCR strategy has gained increasing popularity because all reagents needed for both reactions are added together in a single mix, thus reducing the possibility of contamination, a consideration particularly relevant to viral samples analysis. We describe below two protocols using RT-LATE-PCR and provide specific guidelines for the general application of this technique. The first protocol is devised to quantify mRNA from mouse embryos by real-time PCR; the second protocol employs end-point analysis to detect a number of different viral like sequences in a multiplex reaction. PMID- 20300998 TI - Changes in gene expression of caveolin-1 after inflammatory pain using quantitative real-time PCR. AB - This chapter will take the reader through the steps involved in obtaining a gene expression profile using real-time PCR. Real-time PCR is an end-point measure of changes in gene expression that have occurred after a physiological event. It specifically describes the process by which real-time PCR was used to measure caveolin-1 gene expression after an inflammatory pain insult. The method outlines the initial stage of total RNA extraction from the starting material through the main steps involved in producing a gene expression profile including primer design, RNA quantification and cDNA production by reverse transcription and of course the real-time PCR. The caveolin-1 gene measured here is the main component of specialised domains found in the plasma membrane with a primary function described as signal transduction 'hot spots'. The result of this experiment shows that there was a twofold increase in caveolin-1 gene expression in rat dorsal root ganglions 24 h after Complete Freund's Adjuvant administration and a decrease at 48 h. PMID- 20300999 TI - Real-time quantitative reverse transcriptase polymerase chain reaction. AB - The real-time quantitative reverse transcriptase polymerase chain reaction (RQ PCR) has become the method of choice for the quantification of specific mRNAs. This method is fast, extremely sensitive, and accurate, requires only very small amounts of input RNA, and is relatively simple to perform. These characteristics have made it the method of choice for minimal residual disease monitoring such as in chronic myelogenous leukemia (CML). CML comprises approximately 20% of all leukemias and is characterized by a balanced (9;22) chromosomal translocation that results in the formation of a chimeric gene comprised of the BCR (breakpoint cluster region) gene and the ABL oncogene (BCR-ABL fusion gene). The chimeric gene encodes a fusion protein with constitutively increased tyrosine kinase activity, resulting in growth factor-independent proliferation. This kinase is the target for current CML therapy, and BCR-ABL fusion gene levels are monitored to determine the effectiveness of this therapy. This chapter uses BCR-ABL transcript detection to illustrate an example for the RQ-PCR and describes a RQ PCR method to detect the most common form of the BCR-ABL fusion transcript in CML, known as p210 BCR-ABL. PMID- 20301000 TI - The use of comparative quantitative RT-PCR to investigate the effect of cysteine incubation on GPx1 expression in freshly isolated cardiomyocytes. AB - Intracellular cysteine availability is one of the major rate limiting factors that regulate the synthesis of the major antioxidant, glutathione. Little is known, however, about the effect of cysteine upon glutathione-associated enzymes in isolated heart cells. Such knowledge is important if a full understanding and exploitation of cysteine's cardioprotective potential is to be achieved. Therefore, this study describes the use of a comparative quantitative reverse transcription polymerase chain reaction (RT-PCR) assay to investigate the effect of incubation of freshly isolated rat cardiomyocytes for 2 h at 37 degrees C with or without 0.5 mM cysteine on the expression of cellular glutathione peroxidase (GPx1). The main analytical method is the conventional RT-PCR in a standard thermal cycler followed by electrophoresis and scanning densitometry using the expression of the housekeeping gene, glyceraldehyde-3-phosphate dehydrogenase (GAPDH), for normalising purposes. Each step of this straight-forward and relatively inexpensive method is explained in detail to facilitate its adoption by the reader for experiments investigating the effects of any compound on any gene in any cell population. The results of the current investigation show that cysteine incubation significantly increases the expression of GPx1 in freshly isolated cardiomyocytes compared to control, suggesting the possibility of a new beneficial role for cysteine in myocardial protection. PMID- 20301001 TI - The renaissance of competitive PCR as an accurate tool for precise nucleic acid quantification. AB - Here, we report a detailed procedure for the exact quantification of minute amounts of nucleic acids by competitive PCR. This technique entails the co amplification of a target DNA or cDNA in a biological sample together with a known quantity of a target-specific standard, the competitor, which is added exogenously to the sample and is almost identical to the DNA region to be amplified. Competitive PCR offers the advantage to render the PCR reaction independent of the number of amplification cycles, since any intra-assay variation has the same effect on both target and competitor. Since the final ratio between target and competitor amplification products exactly reflects the initial ratio between the two species, and being the amount of added competitor known, competitive PCR allows the determination of the exact number of molecules of target, with an accuracy that is still unsurpassed by any other alternative procedure, including real-time PCR. The protocols described in this chapter cover most of the possible applications of competitive PCR, including the quantification of an mRNA transcript and the simultaneous determination of multiple targets. PMID- 20301002 TI - Skeletal muscle RNA extraction in preparation for RT-PCR. AB - Extraction of high quality RNA is paramount to successful RT-PCR, and here, a method proven optimal for skeletal muscle is described. While this method described is for use with skeletal muscle, it could be suitable for other types of mammalian tissue also. This method describes an approach to extract high quality RNA with minimal degradation and the subsequent analysis of that RNA in preparation for RT-PCR. Two separate methods of RNA quantification and analysis are described in this chapter and regardless of the method chosen for quantitation and analysis, it is imperative that the integrity of the sample be established before proceeding to RT-PCR. PMID- 20301003 TI - Reverse transcription of the ribonucleic acid: the first step in RT-PCR assay. AB - Reverse transcription (RT) is the synthesis of complementary deoxyribonucleic acids (DNA) from single-stranded ribonucleic acid (RNA) templates. This process is catalyzed by the reverse transcriptase enzyme, which is the replicating enzyme of retroviruses. Reverse transcriptase was discovered in 1970, and since then, it has played an instrumental role in the advancement of molecular biology and biotechnology research. In the presence of all four deoxynucleotides (dNTP: dATP, dCTP, dGTP, and dTTP) and under well-defined salt and pH conditions, the reverse transcriptase extends a primer complementary to the RNA to produce a complementary DNA (cDNA) for the RNA template. In this chapter, a simple method of reverse transcription of total cellular RNA into cDNA is described using Superscript II reverse transcriptase (Invitrogen); the resulting cDNA can be used in polymerase chain reaction (PCR). PMID- 20301004 TI - Primer design for RT-PCR. AB - Primer design is a crucial initial step in any experiment utilizing PCR to target and amplify a known nucleotide sequence of interest. Properly designed primers will increase PCR amplification efficiency as well as isolate the targeted sequence of interest with higher specificity. Many factors that may limit the success of a primer pair can be detected a priori with computational methods. For example, primer dimer detection, amplification of alternative products, stem loop interference, extreme melting temperatures, and genotype-specific variations in the target sequence can all be considered computationally to minimize subsequent PCR failures. The use of computational sequence analysis tools to select the best primer pair from the available candidates will not only reduce experimental rates of failure but also avoid the generation of misleading results arising from the amplification of alternative products. PMID- 20301005 TI - Hot start PCR. AB - Hot Start activation approaches are increasingly being used to improve the performance of PCR. Since the inception of Hot Start as a means of blocking DNA polymerase extension at lower temperatures, a number of approaches have been developed that target the essential reaction components such as magnesium ion, DNA polymerase, oligonucleotide primers, and dNTPs. Herein, five different Hot Start activation protocols are presented. The first method presents the use of barriers as a means of segregating key reaction components until a Hot Start activation step. The second and third protocols demonstrate Hot Start approaches to block DNA polymerase activity through the use of anti-DNA polymerase antibodies and accessory proteins, respectively. The fourth and fifth protocols utilize thermolabile chemical modifications to the oligonucleotide primers and dNTPs. The results presented demonstrate that all protocols significantly improve the specificity of traditional thermal cycling protocols. PMID- 20301006 TI - Real-time RT-PCR for automated detection of HIV-1 RNA during blood donor screening. AB - Real-time RT-PCR has become the method of choice for automated detection of viral RNA target sequences in the clinical laboratory. Besides commercially available certified test systems, a variety of so-called in-house methods have been described in the literature. Generally, appropriate validation and continuous quality control are mandatory if these in-house-developed assays are used in clinical diagnostics. In this chapter, an in-house HIV-1 real-time RT-PCR assay for blood donor screening is described. The procedure includes the pooling of plasma samples, viral RNA isolation, and subsequent detection of amplification in real-time one-step RT-PCR. The validation considers the specificity, the sensitivity on HIV-1 genomic variants, and the robustness of the assay. PMID- 20301007 TI - Appraisal of memory functioning and memory performance in healthy ageing and early-stage Alzheimer's disease. AB - BACKGROUND/AIMS: To compare memory evaluations in healthy older people and people with Alzheimer's disease (AD) and present standardised individual and dyadic methods for classifying degree of memory awareness in the participants with dementia. METHODS: Cross-sectional study evaluating awareness of memory functioning and performance and providing normative data for healthy individuals and couples, together with comparison data from people with AD. RESULTS: As a group, older people are reasonably accurate raters of their own memory functioning and performance, although considerable individual differences can be observed, and control dyads show good comparative accuracy. Comparing normative data from the control group to data from participants with AD confirms that significant overestimation is a frequent feature among people with dementia, with approximately two-thirds showing this pattern, although significant under estimation is also reliably observed in a small proportion of people with dementia. Different types of measure elicit different profiles of memory awareness in participants with dementia. CONCLUSION: Normative data from older individuals and couples provides useful percentile-based indices for determining level of memory awareness in people with dementia. PMID- 20301008 TI - Impact of exposure to community violence, Hurricane Katrina, and Hurricane Gustav on posttraumatic stress and depressive symptoms among school age children. AB - This study examined the relationship between exposure to Hurricane Gustav and distress among 122 children (ages 7-12) to determine whether that relationship was moderated by prior experiences with Hurricane Katrina and exposure to community violence (ECV). Measures of hurricane experiences, ECV, posttraumatic stress (PTS) symptoms, and depression were administered. Assessments occurred after the third anniversary of Katrina, which coincided with the landfall of Gustav. Results indicated that the relation between exposure to Gustav and PTS was moderated by prior experiences. There was a positive association between Gustav exposure and PTS for children who experienced high Katrina exposure and low ECV, with a similar trend for children with high ECV and low Katrina exposure. There was no relationship between Gustav exposure and PTS for children with low Katrina and low ECV or for children with high Katrina and high ECV. The relationship between exposure to Gustav and depression was not moderated by children's prior experience. However, there was a relationship between Katrina exposure and depression for children with high ECV. Results suggest that prior trauma may amplify the relationship between hurricane exposure and distress, but children with high cumulative trauma may remain highly symptomatic regardless of disaster exposure. PMID- 20301010 TI - Event-based prospective memory in children with sickle cell disease: effect of cue distinctiveness. AB - Event-based prospective memory (EB-PM) is the formation of an intention and remembering to perform it in response to a specific event. Currently, EB-PM performance in children with sickle cell disease (SCD) is unknown. In this study, we designed a computer-based task of EB-PM; No-Stroke, Silent-Infarct, and Overt Stroke groups performed significantly below the demographically similar control group without SCD. Cue distinctiveness was varied to determine if EB-PM could be improved. All groups, with the exception of the Overt-Stroke group, performed significantly better with a perceptually distinctive cue. Overall, these results suggest that EB-PM can be improved significantly in many children with SCD. PMID- 20301009 TI - Toddlers with elevated autism symptoms show slowed habituation to faces. AB - We explored social information processing and its relation to social and communicative symptoms in toddlers with Autism Spectrum Disorder (ASD) and their siblings. Toddlers with more severe symptoms of autism showed slower habituation to faces than comparison groups; slower face learning correlated with poorer social skills and lower verbal ability. Unaffected toddlers who were siblings of children with ASD also showed slower habituation to faces compared with toddlers without siblings with ASD. We conclude that slower rates of face learning may be an endophenotype of ASD and is associated with more severe symptoms among affected individuals. PMID- 20301011 TI - Health benefits of whole grain phytochemicals. AB - A whole grain consists of the intact, ground, cracked, or flaked caryopsis, whose principal anatomical components--the starchy endosperm, germ, and bran--are present in the same relative proportions as they exist in the intact caryopsis. Whole grain food products can be intact, consisting of the original composition of bran, germ, and endosperm, throughout the entire lifetime of the product, or reconstituted, in which one or more of the original components of a whole grain is recombined to the relative proportion naturally occurring in the grain kernel. Increased consumption of whole grains has been associated with reduced risk of major chronic diseases including cardiovascular disease, type II diabetes, and some cancers. Whole grain foods offer a wide range of phytochemicals with health benefits that are only recently becoming recognized. The unique phytochemicals in whole grains are proposed to be responsible for the health benefits of whole grain consumption. In this paper, whole grain phytochemicals and the health benefits associated with their consumption are reviewed. PMID- 20301012 TI - Implications of salt and sodium reduction on microbial food safety. AB - Excess sodium consumption has been cited as a primary cause of hypertension and cardiovascular diseases. Salt (sodium chloride) is considered the main source of sodium in the human diet, and it is estimated that processed foods and restaurant foods contribute 80% of the daily intake of sodium in most of the Western world. However, ample research demonstrates the efficacy of sodium chloride against pathogenic and spoilage microorganisms in a variety of food systems. Notable examples of the utility and necessity of sodium chloride include the inhibition of growth and toxin production by Clostridium botulinum in processed meats and cheeses. Other sodium salts contributing to the overall sodium consumption are also very important in the prevention of spoilage and/or growth of microorganisms in foods. For example, sodium lactate and sodium diacetate are widely used in conjunction with sodium chloride to prevent the growth of Listeria monocytogenes and lactic acid bacteria in ready-to-eat meats. These and other examples underscore the necessity of sodium salts, particularly sodium chloride, for the production of safe, wholesome foods. Key literature on the antimicrobial properties of sodium chloride in foods is reviewed here to address the impact of salt and sodium reduction or replacement on microbiological food safety and quality. PMID- 20301013 TI - Intake of added sugars and selected nutrients in the United States, National Health and Nutrition Examination Survey (NHANES) 2003-2006. AB - In the Institute of Medicine (IOM) macronutrient report the Committee recommended a maximal intake of < or = 25% of energy from added sugars. The primary objectives of this study were to utilize National Health and Nutrition Examination Survey (NHANES) to update the reference table data on intake of added sugars from the IOM report and compute food sources of added sugars. We combined data from NHANES with the United States Department of Agriculture (USDA) MyPyramid Equivalents Database (MPED) and calculated individual added sugars intake as percent of total energy then classified individuals into 8 added sugars percent energy categories, calculated usual intake with the National Cancer Institute (NCI) method, and compared intakes to the Dietary Reference Intakes (DRIs). Nutrients at most risk for inadequacy based on the Estimated Average Requirements (EARs) were vitamins E, A, C, and magnesium. Nutrient intake was less with each 5% increase in added sugars intake above 5-10%. Thirteen percent of the population had added sugars intake > 25%. The mean g-eq added sugars intake of 83.1 g-eq/day and added sugars food sources were comparable to the mid 1990s. Higher added sugars intakes were associated with higher proportions of individuals with nutrient intakes below the EAR, but the overall high calorie and the low quality of the U.S. diet remained the predominant issue. With over 80% of the population at risk for select nutrient inadequacy, guidance may need to focus on targeted healthful diet communication to reach the highest risk demographic groups for specific life stage nutrient inadequacies. PMID- 20301014 TI - Policosanols as nutraceuticals: fact or fiction. AB - Policosanols (PC) are very long chain aliphatic alcohols derived from the wax constituent of plants. In the early 1990s, researchers at Dalmer Laboratories in La Habana Cuba isolated and produced the first PC supplement from sugarcane wax. The original PC supplement has been approved as a cholesterol-lowering drug in over 25 countries throughout the Caribbean and South America. Cuban studies claim that 1 to 20 mg/day of the original PC supplement are effective at producing significant reductions in total cholesterol (TC) and low density lipoprotein cholesterol (LDL-C). These studies also show that PC supplements are potent antioxidants, promote proper arterial endothelial cell function, inhibit platelet aggregation and thrombosis, and serve as effective treatments for intermittent claudication. However, for the most part, those studies reporting therapeutic efficacy of PC were carried out by one research group situated in Cuba. Conversely, research groups outside of Cuba have failed to validate the cholesterol-lowering and antioxidant efficacy of PC. Cuban researchers, however, continue to claim that the efficacy is attributed to the unique purity and composition of the original PC preparation, a mixture not found in PC products used by external research groups. The absence of independent and external studies confirming the therapeutic benefits of PC in disease prevention and treatment raises questions regarding their true efficacy. PMID- 20301015 TI - Coenzyme Q10 contents in foods and fortification strategies. AB - Coenzyme Q10 (CoQ(10)) is an effective natural antioxidant with a fundamental role in cellular bioenergetics and numerous known health benefits. Reports of its natural occurrence in various food items are comprehensively reviewed and critically evaluated. Meat, fish, nuts, and some oils are the richest nutritional sources of CoQ(10), while much lower levels can be found in most dairy products, vegetables, fruits, and cereals. Large variations of CoQ(10) content in some foods and food products of different geographical origin have been found. The average dietary intake of CoQ(10) is only 3-6 mg, with about half of it being in the reduced form. The intake can be significantly increased by the fortification of food products but, due to its lipophilicity, until recently this goal was not easily achievable particularly with low-fat, water-based products. Forms of CoQ(10) with increased water-solubility or dispersibility have been developed for this purpose, allowing the fortification of aqueous products, and exhibiting improved bioavailability; progress in this area is described briefly. Three main fortification strategies are presented and illustrated with examples, namely the addition of CoQ(10) to food during processing, the addition of this compound to the environment in which primary food products are being formed (i.e. animal feed), or with the genetic modification of plants (i.e. cereal crops). PMID- 20301016 TI - Clostridium botulinum in cattle and dairy products. AB - The use of plastic-wrapped and nonacidified silage as cattle feed has led to an increasing number of botulism outbreaks due to Clostridium botulinum Groups I-III in dairy cattle. The involvement of Groups I and II organisms in cattle botulism has raised concern of human botulism risk associated with the consumption of dairy products. Multiplication of C. botulinum in silage and in the gastrointestinal tract of cattle with botulism has been reported, thus contamination of the farm environment and raw milk, and further transmission through the dairy chain, are possible. The standard milk pasteurization treatment does not eliminate spores, and the intrinsic factors of many dairy products allow botulinal growth and toxin production. Although rare, several large botulism outbreaks due to both commercial and home-prepared dairy products have been reported. Factors explaining these outbreaks include most importantly temperature abuse, but also unsafe formulation, inadequate fermentation, insufficient thermal processing, post-process contamination, and lack of adequate quality control for adjunct ingredients were involved. The small number of outbreaks is probably explained by a low incidence of spores in milk, the presence of competitive bacteria in pasteurized milk and other dairy products, and growth-inhibitory combinations of intrinsic and extrinsic factors in cultured and processed dairy products. PMID- 20301017 TI - Aloe vera as a functional ingredient in foods. AB - The main scientific discoveries on Aloe vera published mainly in the last three decades are presented in this work. After describing Aloe from a botanical point of view, the papers related with the chemical composition of different parts of the leaf of Aloe, particularly those in which the gel is described and are presented in a synthetic manner. The chemical analyses reveal that Aloe gel contains mannose polymers with some glucose and other sugars, among which the most important is Acemannan. Besides these, other components such as glycoproteins, enzymes, amino acids, vitamins, and minerals are described. Different factors also affecting the chemical composition of the gel, such as species and variety, climatic and soil conditions, cultivation methods, processing and preservation, are enumerated and discussed. On the other hand, the main therapeutic applications have been revised and the possible damaging effects of Aloe are also commented upon. A special emphasis is placed on the biologically active compounds or groups of compounds responsible for the therapeutic applications and which are their action mechanisms. The paper concludes that more research is needed to confirm the therapeutic and beneficial effects and to definitively clarify the myth surrounding Aloe vera. A general view on the problem of the commercialization and establishment of the quality and safety of Aloe products in the food industry has been offered here. The main points and European regulations that need to be considered regarding the quality control of prepared Aloe products are presented in this paper. PMID- 20301018 TI - Reliability and maintainability analysis of bread production line. AB - The statistical analysis of the bread production line of the failure and repair data at machine and line levels was displayed. The experiment covers a period of twenty-five months. The best fit of the failure data between the common theoretical distributions was found and its parameters were computed. The reliability and hazard rate modes for all machines and the entire production line were calculated as well. The models could prove to be a useful tool to assess the current conditions, and to predict the reliability for upgrading the maintenance policy of the production line. It was pointed out that (a) the availability of the bread production line is 90.74% and went down to 86.76% because the equipment's failures cause an additional production gap in the line, (b) the 53.5% of all failures occurred at the bread machine, cooling tower machine, and volumetric-divider machine, and (c) the machines of the bread production line that displayed increasing hazard rate functions were identified. This analysis will be very useful in terms of identifying the occurring and latent problems in manufacturing process of bread and improve it. PMID- 20301019 TI - Modeling thermophysical properties of food under high pressure. AB - A set of well-known generic models to predict the thermophysical properties of food from its composition at atmospheric conditions was adapted to work at any pressure. The suitability of the models was assessed using data from the literature for four different food products, namely tomato paste, potato, pork, and cod. When the composition of the product considered was not known, an alternative was proposed if some thermal data at atmospheric conditions were available. Since knowledge on the initial freezing point and ice content of food are essential for the correct prediction of its thermal properties, models for obtaining these properties under pressure were also included. Our results showed that good predictions under pressure, accurate enough for most engineering calculations can be made, either from composition data or using known thermal data of the food considered at atmospheric conditions. All the equations and coefficients needed to construct the models are given throughout the text, thus readers can compose their own routines. However, these routines can also be downloaded free at http://www.if.csic.es/programas/ifiform.htm as executable programs running in Windows. PMID- 20301020 TI - Contextual factors influencing HIV risk behaviour in Central Asia. AB - Central Asia has experienced a rapid increase in HIV. HIV interventions and prevention programmes are needed that adequately appreciate and account for the ways that ongoing cultural, political and economic changes in this region affect HIV risk reduction efforts. Drawing on relevant literature, this paper provides a contextual foundation to better understand the impact of context on HIV risk behaviour in the countries of Central Asia and to begin the conversation on the contextual factors of Islam and polygamy. PMID- 20301021 TI - Comparison of long-term results of drug-eluting stent and bare metal stent implantation in heart transplant recipients with coronary artery disease. AB - BACKGROUND: Transplanted heart coronary artery disease (TxCAD) may occur in a significant proportion of patients following cardiac transplantation. Drug eluting stents (DES) have been successfully used in patients with CAD, but their efficacy in TxCAD patients has not been well established. AIM: To compare long term results of intracoronary implantation of DES and BMS in patients suffering from TxCAD. METHODS: We performed a retrospective analysis of all intracoronary stent implantations for TxCAD with at least one control coronary angiography performed during follow-up. We identified 28 DES (all sirolimus-eluting stents, SES) and 28 BMS implantations in 23 patients. The mean follow-up time was 410+/ 58 days after DES, and 572+/-434 days after BMS implantation (p=0.004). We compared the occurrence of in-stent restenosis (ISR) in DES and BMS, and survival of patients in the context of risk factors that were identified for each stent implantation separately. RESULTS: There were 2 (7%) ISR revealed in DES patients (mean time from PCI to restenosis 492+/-58 days) vs. 17 (61%) ISR in BMS patients (mean time from PCI to restenosis 475+/-345 days) (p<0.001). There were 3 (18%) deaths in patients with DES, 4 (31%) in patients with BMS, and 1 (14%) in a patient with DES and BMS (NS). The risk factor profile was comparable, except for higher age at the time of transplantation (46+/-7 vs. 41+/-6 years, p=0.011) and stent implantation (54+/-7 vs. 49+/-6 years, p<0.001) for DES. CONCLUSION: Favourable long-term results of DES compared with BMS implantation for TxCAD suggest the preferential use of DES in heart transplant recipients. PMID- 20301022 TI - The combined pharmacological stress echocardiography protocol for predicting viability in territories supplied by coronary arteries at varying degrees of obstruction. AB - BACKGROUND: Pharmacological stress echocardiography has gained wide acceptance for identification of myocardial viability. AIM: We sought to explore the diagnostic accuracy of the combined pharmacological stress echocardiography protocol to predict viability of myocardial segments supplied by arteries at varying degrees of stenosis/occlusion. METHODS: We enrolled 100 consecutive patients with significant coronary stenosis/occlusion, prior myocardial infarction, and regional wall motion abnormality in the distribution of the affected artery. All patients underwent assessment of global and regional left ventricular systolic function. Patients underwent 3 pharmacological stress echocardiography protocols: low dose dobutamine, infra-low dose dipyridamole, and combined protocols. They underwent thereafter successful coronary revascularisation either by percutaneous coronary angioplasty, or by surgical bypass grafting. Follow-up echocardiography was performed 8 weeks later. Segments were subdivided according to the severity of stenosis/occlusion of the supplying artery into 3 subgroups, namely: those supplied by totally occluded, critically stenosed, or subcritically stenosed arteries. Predicted recovery by any of the 3 protocols for each category of segments was compared with real contractility improvement after revascularisation. RESULTS: The combined protocol had a significantly higher sensitivity for predicting contractile recovery in all segment categories compared with the other 2 protocols. In addition, it had a similar specificity in segments supplied by subcritically stenosed arteries, though with a lower specificity in segments supplied by totally occluded and critically stenosed arteries when compared with the other two protocols. CONCLUSION: The combined pharmacological stress protocol would better predict viability, as compared to the low dose dobutamine and the infra-low dose dipyridamole protocols, particularly in segments supplied by subcritically stenosed arteries. PMID- 20301023 TI - Determinants of physical fitness in males with systolic heart failure. AB - BACKGROUND: Heart failure (HF) is a systemic disease which affects mainly older adults. The main symptom of HF is exercise intolerance which in the course of disease can cause limitations in independent functioning. So far no study on the impact of HF on physical fitness in men, regardless of disease severity, has been reported. AIM: To evaluate physical fitness in men with HF independently of age, HF severity, concomitant diseases and pharmacological treatment. METHODS: The study group consisted of 228 men with stable systolic dysfunction (age 60+/-11, left ventricular ejection fraction--LVEF 29+/-9%, NYHA class I/II/III/IV- 17/44/35/4%). In order to assess physical fitness the Functional Fitness Test by Rikli and Jones for older adults was used. RESULTS: The level of physical fitness decreased with age. Patients with greater severity of HF had worse aerobic endurance, agility and muscular endurance in comparison with men in NYHA classes I-II. A lower level of agility and dynamic balance was found in patients with higher concentration of NT-proBNP and lower levels of haemoglobin and eGFR. Coexisting atrial fibrillation and diabetes mellitus were associated with decreased physical fitness. No relationship between flexibility and clinical parameters or concomitant diseases was found in the study group. CONCLUSIONS: The most important determinants of physical fitness in men with HF were age and NYHA class. Additional factors which decreased physical fitness were atrial fibrillation and diabetes mellitus. Higher level of NT-proBNP and lower levels of haemoglobin were associated with a reduction of upper body strength and aerobic endurance. PMID- 20301024 TI - The clinical course of acute ST-elevation myocardial infarction in patients with hypertension. AB - BACKGROUND: Arterial hypertension has been documented as one the cardiovascular risk factors. The issue whether hypertension worsens the clinical course and short-term prognosis of patients with acute ST-elevation myocardial infarction (STEMI) has been addressed by several studies, however, the results were not uniform. AIM: To compare the clinical course and short-term prognosis in STEMI patients with or without hypertension. METHODS: The study group consisted of 366 patients with STEMI, of whom 234 (63.9%) had a history of hypertension (150 males, mean age 58.5+/-11.2 years) whereas 132 (100 males, mean age 60.3+/-11.9) did not. All patients underwent primary angioplasty with stent implantation. Details from medical history, cardiovascular risk factors, clinical course and in hospital complications were recorded and compared between patients with and without hypertension. RESULTS: There were differences between both study groups in the prevalence of cardiovascular risk factors. Patients with hypertension had more frequently history of coronary artery disease (56 vs. 37%, p<0.01), BMI>25 kg/m2 (90 vs. 85%, p<0.01), type 2 diabetes (27 vs. 14%, p<0.05), hyperlipidaemia (56 vs. 43%, p<0.05), and renal disease (11 vs. 5%, p<0.05). Clinical course of MI was more complicated in patients with hypertension who had more often cardiogenic shock (10 vs. 6%, p<0.05), pulmonary oedema (12 vs. 4%, p<0.05), sinus tachycardia>90 beats/min on admission (12 vs. 4%, p<0.05), ventricular tachycardia or fibrillation (20 vs. 11%, p<0.01) and complete atrioventricular block (11 vs. 4%, p<0.01). In-hospital deaths occurred in 18 (7.7%) patients with hypertension and 7 (5.3%) patients without hypertension (NS). Multivariate analysis identified age>65 years, symptoms of heart failure, atrial fibrillation, elevated blood glucose level and creatinine level as independent prognostic factors of adverse outcome in both groups whereas history of stroke, increased while cell blood count, urea level and two-vessel disease where independent prognostic variables in patients with hypertension. Ventricular tachycardia or fibrillation had prognostic significance only in STEMI patients without hypertension. CONCLUSION: Patients with STEMI and hypertension have more cardiovascular risk factors and more complicated in-hospital course of MI than normotensive patients. PMID- 20301025 TI - Off-pump coronary artery bypass surgery can be completed safely in high risk patients. AB - BACKGROUND: Off-pump coronary artery bypass (OPCAB) grafting has the potential to reduce morbidity and mortality, compared to on-pump cardiac surgery. AIM: We compared the early results of OPCAB lateral and posterior wall revascularisations in 'low', 'intermediate' and 'high' risk patients as defined by the EuroSCORE system. METHODS: Eighty-nine patients who underwent OPCAB with lateral and posterior wall revascularisation from January 2006 to December 2008 were included in this study. Patients were allocated to one of the three risk groups according to the EuroSCORE system: low, moderate and high risk groups. Perioperative and early postoperative results of the three groups were compared. RESULTS: Significantly fewer patients required prolonged ICU stay in the low risk group, compared to moderate (19.4 vs. 50%) and high risk groups (19.4 vs. 36.7%). In addition, prolonged mechanical ventilation was more common in moderate (39.3 vs. 9.7%) and high risk groups (36.7 vs. 9.7%), compared to the low risk group. However, the groups did not differ in terms of mortality or other perioperative outcomes. CONCLUSIONS: Our results suggest that in patients who are considered high risk on the basis of the EuroSCORE model and have diseased vessels on the lateral and/or posterior walls of the heart suitable for grafting, the early outcomes with OPCAB are similar to those in medium or low EuroSCORE risk category. The EuroSCORE model may overestimate the risk for OPCAB procedures. PMID- 20301026 TI - Evaluation of safety and the success rate of cryoballoon ablation of the pulmonary vein ostia in patients with atrial fibrillation--a preliminary report. AB - BACKGROUND: Cryoballon isolation of the pulmonary veins has recently emerged as a promissing technique for ablation of atrial fibrillation (AF). AIM: To present our initial experience in cryoballon isolatin of the pulmonary veins in patients with AF. METHODS: Eight patients (5 males; age 59+/-2 years) with AF: 2 with persistent and 6 with paroxysmal (5 of them after unsuccessful RF ablation) with >or=6 month follow-up after the procedure were included. One patient after myocardial infarction was treated with primary angioplasty with stent implantation. Another one had biatrial pacemaker. The procedure was performed with cryobaloon with 28 mm diameter (Arctic Front--Cryocath). After transseptal puncture mapping of the pulmonary vein ostia was performed with Lasso catheter (Johnson and Johnson). At each pulmonary vein ostium with pulmonary vein potentials 2 cryoapplications of 300 s duration was performed. Correct balloon placement before cryoapplication was checked using contrast injection into the pulmonary veins. During cryoapplication in the right pulmonary vein ostia permanent pacing of the phrenic nerve 30 beats per minute was performed to prevent its paralysis. After cryoapplications in all veins remapping with Lasso catheters was performed. In the absence of pulmonary vein potentials the procedure was finished, otherwise next cryoapplications were performed. During follow-up ECG was performed if any palpitations occurred, and 24-hour Holter monitoring was performed 1, 2 ,4, 6, 8, 10 and 12 months after the procedure. A 2 month blanking period after the procedure was used. The lack of symptomatic AF and the absence of AF>30 s on Holter ECG monitoring were defined as successful procedure. An improvement was defined as reduction of frequency/duration of AF paroxysm and reduction of the EHRA index>or=1. RESULTS: During 8 procedures isolation of 31 pulmonary vein was performed. Procedure duration was 3.5+/-0.85 h, fluoroscopy time--33.55+/-15.44 min, and total cryoapplication time--38.33+/ 4.1 min. There were no complications. After the follow-up of 8.5+/-0.99 months 6 (75%) patients were free from arrhythmia, including the patient after myocardial infarction and one patient with permanent AF prior ablation. In another patient an improvement was observed (EHRA score II/III to I) whereas in one patient with permanent AF the procedure was unsuccessful. CONCLUSION: Cryoballoon ablation of pulmonary vein ostia is effective and safe, and can be an alternative to RF ablation. Easier procedure technique make possible shortening of the learning curve and increase the number of treated patients. PMID- 20301027 TI - 'Sandwich patch technique' to repair multiple trabecular ventricular septal defects--a case report. AB - In the case of multiple trabecular ventricular septal defects, it is difficult to identify the exact locations and margins because of trabeculations of the right ventricle. It is also well known that ventriculotomy for closure of ventricular septal defects sometimes causes postoperative ventricular dysfunction or arrhythmia. To overcome these problems, we used the 'sandwich patch technique' to repair multiple trabecular ventricular septal defects. PMID- 20301028 TI - [Patient with Ebstein anomaly treated by Carpentier's technique tricuspid valve repair--a case report]. AB - Ebstein anomaly is a congenital tricuspid valve and right ventricle malformation characterised by posterior and/or septal leaflet deformation that are malpositioned. The target of surgical intervention is to restore tricuspid valve function with right ventricle preservation but also to decrease the risk of cardiac arrhythmias. We present a case of a 56-year-old female patient with type C Ebstein anomaly. She underwent successful procedure of tricuspid valve repair with biodegradable ring. PMID- 20301029 TI - [Effective treatment of recurrent infective endocarditis. Is it always in compliance with the guidelines?]. AB - We present a case of recurrent infective endocarditis (IE) in a 36-year-old man, localised on native congenital bicuspid aortic valve and an acquired membranous ventricular septal defect with vegetations extending to the right ventricle. Patient was successfully treated with standard therapy for IE due to staphylococci MSSA followed by aortic valve replacement and closure of ventricular septal defect. PMID- 20301030 TI - [Acute aortic dissection type A in a 28-year-old woman 10 days after delivery]. AB - A case of a 28-year-old women, with acute aortic dissection type B, ten days after childbirth is described. The pregnancy was ended by cesarean section. The patient underwent successful stent grafting. A subsequent one-month follow-up period was uneventful. Diagnosis and treatment of acute aortic dissection are discussed. PMID- 20301031 TI - [Sleep apnea syndrome or atrio-ventricular block and hypertension?]. AB - A case of hypertensive patient with obstructive sleep apnea syndrome is presented. The third degree atrio-ventricular block was detected during diagnostic procedure and treatment of blood pressure in patient with obstructive sleep apnea. A heart pacemaker has been implanted. After this procedure the sleep apnea signs have not been detected. PMID- 20301032 TI - [The role of DNA methylation in etiopathology of coronary heart diseases]. PMID- 20301033 TI - [The role of cardiovascular magnetic resonance imaging in dilated cardiomyopathy]. PMID- 20301034 TI - [Acute coronary syndrome in a patient with Wolff-Parkinson-White syndrome--a case report]. AB - A case of a 59-year-old man with acute coronary syndrome and ECG features of WPW syndrome is described. The typical chest pain and release of myocardial necrosis markers were accompanied by ECG signs of preexcitation. Angiography revealed significant lesions in coronary arteries. Difficulties in ECG diagnosis of acute myocardial infaction in the presence of preexicitation are disscussed. PMID- 20301035 TI - Isolated cardiac hydatidosis--a case report. AB - Cardiac hydatidosis is rarely encountered. A case of isolated cardiac hydatid cyst of the left ventricle in a young woman is described. The diagnosis was suggested by echocardiography and was confirmed later by pathological evaluation. Serological tests were negative. The patient underwent a successful operation for cyst resection. PMID- 20301036 TI - [Percutaneous revascularisation of subacute occlusion of the left subclavian artery manifesting as acute coronary syndrome in a patient after coronary artery bypass grafting]. AB - A case of subacute occlusion of the left subclavian artery (LSA) manifesting as acute coronary syndrome and associated with coronary-subclavian steal syndrome (CSSS) in a 56-year-old man following coronary artery bypass grafting (CABG) is presented. Complex percutaneous angioplasty with stenting of the LSA and left vertebral artery were successfully performed. In this article, the clinical management of unstable post-CABG patients with occlusion of the subclavian artery is discussed. PMID- 20301037 TI - [Contribution of atrioventricular node inputs on orthodromic atrioventricular reentrant tachycardia cycle length]. AB - We describe a 21-year-old woman with a previous history of orthodromic AVRT and overt preexcitation. Electrophysiological study revealed the presence of a left sided accessory pathway. During an orthodromic AVRT a spontaneous sudden change in heart rate (141 to 202 beats/min) without any change of the QRS morphology was noted due to a decrease in AH interval (from AH=227 ms to AH=100 ms). We explained this phenomenon as the sudden change of the inferior inputs to superior in the AV node. PMID- 20301038 TI - [The 6-minute walking test--clinical usefulness and limitations]. PMID- 20301039 TI - [The role of gerontology in the diagnosis and treatment of cardiovascular diseases]. PMID- 20301040 TI - [Bosenten and sildenafil in the treatment of Eisenmenger syndrome]. PMID- 20301041 TI - [Transcatheter closure of left atrial appendage with the Amplatzer Cardiac Plug in patients with atrial fibrillation and high risk of thromboembolic events- early experience]. AB - BACKGROUND: Atrial fibrillation is the most common arrhythmia in patients beyond 65 years of age. Several of those patients have contraindications to coumadin treatment. Ninety percent of atrial thrombi related to atrial fibrillation are found in the left atrial appendage. AIM: We present our early experience with the left atrial appendage transcatheter closure using the Amplatzer Cardiac Plug. METHODS: Transcatheter closure was performed in general anaesthesia and under transoesophageal echocardiography control in three patients aged 69, 73 and 61 years (two female). All had atrial fibrillation with high risk of thromboembolic events (CHADS2 score 2 points). In all of them coumadin treatment was contraindicated. RESULTS: The procedure time was 112, 109 and 60 min (fluoroscopy time: 25, 29 and 12.5 min). The Amplatzer Cardiac Plugs of 24, 26 and 22 mm were implanted successfully and without complications. The day after, transthoracic echocardiogram revealed proper position of the implant and complete occlusion of the appendage in all patients. The patients were discharged on antiplatelet treatment. CONCLUSION: Transcatheter left atrial appendage closure with the Amplatzer Cardiac Plug may be a promising therapeutic option for patients with atrial fibrillation-related high risk of thromboembolic events and with contraindications to anti-vitamin K treatment. PMID- 20301042 TI - Activity profile in elite Italian soccer team. AB - The purpose of this study was to analyse the activity profile of players in a top class team in the Italian national football league over the course of a season (n=388). The effect of playing position and the two halves on the number and duration of short, intense bursts of effort and recovery phases was studied. The main results show that midfielders cover significantly more distance than players in other positions (p<0.001). For midfielders, the number of displacements of 2 40 m and the number of sprints covering between 2 and 9 m and between 30 and 40 m are considerably greater than for other positions (p<0.05). The distances covered in the second half compared to the first half are significantly lower for all categories of run (p<0.05). In the second half, the distance covered at very high intensity is significantly lower (p<0.01), whilst the number of recovery times greater than 120 s increases significantly compared to the first half (p<0.01). This study provides data which could be used as a basis for the work of scientists as well as football professionals. PMID- 20301043 TI - Knee proprioception after exercise-induced muscle damage. AB - The purpose of the present study was to investigate whether exercise-induced quadriceps muscle damage affects knee proprioception such as joint position sense (JPS), force sense and the threshold to detect passive movement (TTDPM). Fourteen young men performed sets of eccentric quadriceps contractions at a target of 60% of the maximal concentric peak torque until exhaustion; the exercise was interrupted whenever the subject could not complete two sets. Muscle soreness, JPS, the TTDPM and force sense were examined before the exercise as well as one, 24, 48, 72 and 96 h after exercise. The results were compared using one-way repeated-measure ANOVA. Plasma CK activity, collected at the same times, was analyzed by the Friedman's test to discriminate differences between baseline values and each of the other assessment moments (p<0.05). Relative to the proprioception assessment, JPS at 30 and 70 degrees of knee flexion and force sense were significantly decreased up to 48 h, whereas TTDPM decreased significantly at only one hour and 24 h after exercise, at 30 and 70 degrees of the knee flexion, respectively. The results allow the conclusion that eccentric exercise leading to muscle damage alters joint proprioception, suggesting that there might be impairment in the intrafusal fibres of spindle muscles and in the tendon organs. PMID- 20301044 TI - Bone mass in prepubertal tennis players. AB - To assess if exercise before puberty affects bone mineral content (BMC) and bone mineral density (BMD) we determined BMC and BMD in the dominant arm (DA) and non dominant arm (NDA), lumbar spine and femoral neck in 25 tennis players (TP), 21 soccer players (SP) and 22 physically active controls (CG). All of them were under 12 years of age and prepubertal. In TP the DA was heavier than the NDA (7.5+/-0.8%), due to a greater lean mass (10.2+/-1.2%) and BMC (16.3+/-2.2%). The increased BMC is due to a greater DA bone area (11.1+/-1.9%) and BMD (4.1+/ 0.7%). BMC inter-arm asymmetry was 50-75% of that previously observed in professional TP. Inter-arm asymmetry in lean mass, BMC, BMD and bone area was significantly higher in TP than in SP and CG. Lumbar spine BMC and BMD were similar across groups. TP and CG had similar femoral neck BMDs, whilst SP had higher femoral neck BMD than TP. In conclusion, tennis participation before puberty is associated with increased lean mass and bone mass, due to an enhanced bone size and areal BMD in the playing arm. PMID- 20301045 TI - Examining the accumulated oxygen deficit method in front crawl swimming. AB - The present study investigated the Accumulated Oxygen Deficit (AOD) method in front crawl swimming with the aims to assess the robustness of the oxygen uptake/swimming velocity regression line and to quantify the precision of the AOD. Twenty-nine male swimmers performed two swimming tests in different days, with a 24 h recovery between tests: a graded test and an all-out test. The all out test was performed either in 100 m (n=11), 200 m (n=13) or 400 m (n=5). Through all testing expired gases were collected breath by breath and analysed with a K4b2 Gas Analyser (Cosmed, Rome, Italy) connected to an AquaTrainer Valve (Cosmed, Rome, Italy). The error of oxygen uptake/swimming velocity regression lines was approximately 4-5 ml x kg (-1) x min (-1)) and the regressions allowed an extrapolation of the energy cost to higher intensities with a standard error of prediction of approximately 3-4 ml x kg (-1) x min (-1). However, the data variability was considerable (95% confidence intervals of the linear extrapolation larger than 13 ml x kg (-1) x min (-1)). The AOD imprecision varied among the three distance events from approximately 3-13 ml x kg (-1). These absolute errors are small, considering the time that subjects took to cover the three distances, but relative to the AOD values that were estimated they can be considered high, especially in the 400 m bout. PMID- 20301046 TI - The power profile predicts road cycling MMP. AB - Laboratory tests of fitness variables have previously been shown to be valid predictors of cycling time-trial performance. However, due to the influence of drafting, tactics and the variability of power output in mass-start road races, comparisons between laboratory tests and competition performance are limited. The purpose of this study was to compare the power produced in the laboratory Power Profile (PP) test and Maximum Mean Power (MMP) analysis of competition data. Ten male cyclists (mean+/-SD: 20.8+/-1.5 y, 67.3+/-5.5 kg, V O (2 max) 72.7+/-5.1 mL x kg (-1) x min (-1)) completed a PP test within 14 days of competing in a series of road races. No differences were found between PP results and MMP analysis of competition data for durations of 60-600 s, total work or estimates of critical power and the fixed amount of work that can be completed above critical power (W'). Self-selected cadence was 15+/-7 rpm higher in the lab. These results indicate that the PP test is an ecologically valid assessment of power producing capacity over cycling specific durations. In combination with MMP analysis, this may be a useful tool for quantifying elements of cycling specific performance in competitive cyclists. PMID- 20301047 TI - Effects of repetitive training at low altitude on erythropoiesis in 400 and 800 m runners. AB - Classical altitude training can cause an increase in total hemoglobin mass (THM) if a minimum "dose of hypoxia" is reached (altitude >or=2,000 m, >or=3 weeks). We wanted to find out if repetitive exposure to mild hypoxia during living and training at low altitude (<2,000 m) for several weeks, often performed by elite athletes, might also have significant effects on erythropoiesis. THM, erythropoietin (EPO), soluble transferrin receptor (sTfR) and ferritin were determined in 8 elite runners before and after each of 2 training camps at low altitude interspersed by 3 weeks of sea-level training and at the same time points in a control group (CG) of 5 well-trained runners. EPO, sTfR and ferritin were also repeatedly measured during the altitude training camps. Repeated measures ANOVA revealed significant increases in EPO- and sTfR-levels during both training camps and a significant decrease in ferritin indicating enhanced erythropoietic stimulation during living and training at low altitude. Furthermore, significant augmentation of THM by 5.1% occurred in the course of the 2 altitude training camps. In conclusion, repetitive living and training at low altitude leads to a hypoxia-induced increase in erythropoietic stimulation in elite 400 m and 800 m runners and, apparently, might also cause a consecutive augmentation of THM. PMID- 20301048 TI - Resistance exercise intensity progression in older men. AB - Our purpose was to examine possible influences of age on resistance exercise (RE) intensity progression in men. Twenty-four men, divided in young sedentary (YS; n=10; 25.9+/-3.7 years), older sedentary (OS; n=7; 67.4+/-5.2 years), and older runners (OR; n=7; 71.3+/-3.0 years), underwent a 2 times-a-week RE program for 13 weeks. Muscle strength was assessed before and after training by 1-repetition maximum test. RE workloads were recorded for each exercise session, and increases of 5-10% were made whenever adaptation occurred. Muscle strength improved similarly in all groups after RE (P<0.001). Relative RE intensity progression was not significantly different between YS and OS, except for a greater increase in calf raise relative workload observed in YS (P<0.05). In contrast, OR displayed greater relative workload increase in 7 and 6 exercises than YS and OS, respectively (P<0.05). The RE was safe as no injuries or major muscle pain were observed in either group. These results suggest that healthy sedentary older men are capable to exercise and increase RE intensity in the same way as young men, while physically active older men are capable to increase RE intensity in greater way than sedentary young and older men. PMID- 20301049 TI - Changes in the salivary biomarkers induced by an effort test. AB - Physical exercise induces biochemical changes in the body that modify analytes in blood and saliva among other body fluids. This study analyzed the effect of an incremental effort test on the salivary protein profile to determine whether any specific protein is altered in response to such stress. We also measured thresholds of salivary alpha amylase, total salivary protein and blood lactate and searched for correlations among them. Twelve male cyclists underwent a progressive test in which blood and saliva samples were collected simultaneously at each stage. The salivary total protein profile revealed that physical exercise primarily affects the polypeptide corresponding to salivary alpha-amylase, the concentration of which increased markedly during the test. We observed thresholds of salivary alpha-amylase (sAAT), total salivary protein (PAT) and blood lactate (BLT) in 58%, 83% and 100% of our sample, respectively. Pearson's correlation indicates a strong and significant association between sAAT and BLT (r= 0.84, P<0.05), sAAT and PAT (r= 0.83, P<0.05) and BLT and PAT (r= 0.90, P<0.05). The increased expression of the salivary alpha-amylase (sAA) polypeptide suggests that sAA is the main protein responsible for the increase in total protein concentration of whole saliva. Therefore, monitoring total protein concentration is an efficient tool and an alternative noninvasive biochemical method for determining exercise intensity. PMID- 20301050 TI - [Retraumatization--a conceptional approach]. AB - Characteristics of posttraumatic stress disorder (PTSD) may be influenced by newly experienced traumata or confrontation with trauma-associated stimuli. Terms like reactivation or retraumatization are used either to describe slightly, temporary or severe and permanent increase in PTSD symptoms. Trigger, duration and intensity of a potential increase in symptoms have not been consistently defined yet. The purpose of this overview is to operationalize the term retraumatization on the background of empirical studies and to deduce a standardized definition. Furthermore implications for research and clinical practice are discussed. PMID- 20301051 TI - [Chronic obstructive pulmonary disease (COPD): spouses' quality of life and burden during the course of disease]. AB - Little is known about the effect of chronic diseases like COPD on the well-being of caring partners. The aim of the present study was the prospective longitudinal evaluation of quality of life as well as psychological distress with consideration to further psychosocial variables. Therefore a group of 143 consecutive COPD-outpatients and their spouses (n=105) were followed-up over a period of 3 years to assess changes in quality of life (EuroQol), psychological distress (SCL-90-R) and social support (F-SozU). Complete data were available in 64 couples. Spouses showed reduced quality of life and nearly one out of four reported increased psychological distress. Among others, initial social distress predicted quality of life and psychological distress. Given the results, it is time to take action in order to prevent caring spouses to become dependent on care themselves. PMID- 20301052 TI - From congenital dermal sinus tract to extensive epidural abscess of the spine. PMID- 20301053 TI - Early course of Berardinelli-Seip congenital lipodystrophy (BSCL). AB - Berardinelli-Seip congenital lipodystrophy (BSCL) is a very rare autosomal recessive disease. In the described patient diagnostic relevant symptoms developed at 3 week age. PMID- 20301054 TI - [Skin abscesses in kindergarten children: severe courses due to Panton-Valentine leukocidin producing S. aureus]. PMID- 20301055 TI - Apparently no sedative benzoflavone moiety in passiflorae herba. AB - Due to the fact that an Indian group had reported a benzoflavone moiety (BZF) as an active principle in the herb of Passiflora incarnata L. (Passifloraceae), this study was performed to isolate the compound for analytical purposes. In Passiflorae herba from three different origins (cultivations in India, Italy and France) a compound with the published TLC characteristics was detected in trace amounts only in the Italian material. No traces of the substance were found in the drugs from India and France. In a commercial extract two compounds with the respective TLC characteristics were detected. One was identified as a phytol isomer. Due to the very small amounts of the second compound its structure elucidation was not successful. The amount of extract for the isolation corresponded to approximately the 10-fold amount of the drug, from which the isolation of 332 mg "BZF" had been reported. The detection of only trace amounts of a BZF-like compound in one of three commercial samples of Passiflorae herba and in an extract suggests for the first time that BZF is not the active principle in this drug and should not serve as an active marker. PMID- 20301056 TI - Enhancement of artemisinin content through four cycles of recurrent selection with relation to heritability, correlation and molecular marker in Artemisia annua L. AB - Due to the high demand and low yield of the anti-malarial drug artemisinin in natural populations of Artemisia annua (Quinghao), an attempt has been made to enhance the artemisinin content through 4 cycles of recurrent selection (C(0) C(3)) using selected genotypic and phenotypic traits. Based on their phenotypic and genotypic characteristics, the top 5% plants of each cycle were selected, and their seedlings were planted in poly-cross block to produce seeds for the subsequent generation. A significant increase in the artemisinin content (0.15% in C (0) to 1.16% in C (3), i.e., about 40% genetic gain over the generation) was observed. This enhancement was directly correlated with the plant height and branching intensity in all four cycles. Similarly, the PCV (phenotypic coefficient of variation) and GCV (genotypic coefficient of variation) have been observed to have a higher value for artemisinin content. The DNA marker (MAP 12) with relation to artemisinin was also identified for high yielding genotypes in all four cycles of selection. Over the four cycles of recurrent selection, the plant developed an oval appearance (Variety: CIM-Arogya) and a high artemisinin content (1.16%). PMID- 20301057 TI - Anti-adipogenic activities of Alnus incana and Populus balsamifera bark extracts, part I: sites and mechanisms of action. AB - Obesity is an epidemic in most developed countries and novel therapeutic approaches are needed. In the course of a screening project of medicinal plants used by the Eastern James Bay Cree of Canada and having potential for the treatment of diabetes, we have identified several products that inhibit adipogenesis, suggesting potential antiobesity activities. The inhibitory activity of two of these, the extract of the inner bark of the deciduous trees Alnus incana ssp. rugosa (Speckled Alder) and Populus balsamifera L. (Balsam Poplar), was analyzed using the 3T3-L1 cell model of adipogenesis. Intracellular triglyceride accumulation, pre-adipocyte proliferation, and PPAR- gamma activity were measured. Alnus incana extracts acted early in the differentiation process but did not affect clonal expansion of pre-adipocytes nor the morphological transformation from fibroblast-like to rounded fat-laden cells. Alnus incana extracts were found to act as partial agonists toward PPAR- gamma activity. In contrast, Populus balsamifera extracts completely abrogated adipogenesis, severely limited clonal expansion of pre-adipocytes and generally maintained cells in an undifferentiated fibroblast-like morphology. Populus balsamifera extracts exerted antagonistic action against PPAR- gamma activity. It is concluded that, through their actions on the adipocyte, these plant products may be useful for the treatment of obesity and related metabolic diseases. PMID- 20301058 TI - Anti-adipogenic activities of Alnus incana and Populus balsamifera bark extracts, part II: bioassay-guided identification of actives salicortin and oregonin. AB - Among modern day metabolic diseases, obesity has reached epidemic proportions worldwide and novel therapeutic support strategies are urgently needed. Adipocytes are interesting targets in this context. Using ethnobotanical and bioassay screening techniques, we have identified two Boreal Forest plants used by the James Bay Cree that potently inhibit adipogenesis, namely ALNUS INCANA ssp. RUGOSA (Speckled Alder) and POPULUS BALSAMIFERA (Balsam Poplar). The mode of action of this inhibitory activity was reported in a companion paper. The current study report the results of a classical bioassay-guided fractionation approach aimed at identifying the active principles responsible for the inhibition of adipogenesis, as measured using triglyceride accumulation in the 3T3-L1 adipocyte model cell line. The glycosides oregonin and salicortin were isolated and identified as the respective active principles for ALNUS INCANA and POPULUS BALSAMIFERA. These compounds thus offer promise as novel agents to mitigate the incidence or the progression of obesity. PMID- 20301059 TI - Antitrypanosomal activity of a diterpene and lignans isolated from Aristolochia cymbifera. AB - Bioguided fractionation of extract from the leaves of Aristolochia cymbifera led to the isolation of the furofuran lignans fargesin, epieudesmin, and sesamin; the dibenzylbutyrolactone lignans hinokinin and kusunokinin; and an ENT-labdane diterpene named copalic acid. Our data demonstrated that copalic acid and kusunokinin were the most active compounds against trypomastigotes of Trypanosoma cruzi. Additionally, copalic acid demonstrated the highest parasite selectivity as a result of low toxicity to mammalian cells, despite a considerable hemolytic activity at higher concentrations. Among the isolated compounds, kusunokinin could be considered the most promising candidate, as it displayed significant activity against intracellular amastigotes (IC(50) = 17 uM) and trypomastigotes (IC(50) = 51 uM) without hemolytic activity. Fargesin, hinokinin, epieudesmin, and sesamin were also effective against trypomastigotes, but these compounds were highly toxic to mammalian cells and no parasite selectivity could be identified. The need for novel drugs for American trypanosomiasis is evident, and these secondary metabolites from A. cymbifera represent a useful tool for drug design. PMID- 20301061 TI - [Pay for performance: payment determined by outcome]. PMID- 20301060 TI - Anatomical and technical tips for use of the superficial inferior epigastric artery (SIEA) flap in breast reconstructive surgery. AB - Techniques for autologous breast reconstruction have evolved to minimize donor site morbidity and reduce flap-specific complications. When available, the superficial inferior epigastric artery (SIEA) flap represents the optimal method to achieve the former. However, many microsurgeons have been reluctant to adopt this procedure due to technical challenges inherent to the surgery, as well as concerns with the intrinsic capacity of the superficial vessel system to adequately support this flap. This article sets forth a simple approach to the SIEA flap harvest and demonstrates that favorable results may be achieved even for small caliber vessels. A total of 46 patients underwent 53 SIEA breast reconstructions over a 6-year period using a modified approach for pedicle dissection and arterial inclusion criteria solely on the basis of presence of a palpable pulse. Average pedicle length harvested for all SIEA flaps was 6.07 cm; and mean arterial (0.96 mm) and venous (2.27 mm) diameters represent the lowest published values. Three flaps (5.7%) demonstrated fat necrosis or partial flap necrosis, with one (1.9%) complete flap loss. These results compare favorably with those of previous SIEA series employing diameter-based selection criteria, suggesting that the presence of a palpable arterial pulse may be sufficient to permit successful utilization of this flap. PMID- 20301062 TI - "So what?". PMID- 20301063 TI - Influenza pandemic: a perspective. PMID- 20301064 TI - Evidence-based decision-making (part II): applications in disaster relief operations. AB - Recognized limitations to data in disaster management have led to dozens of initiatives to strengthen data gathering and decision-making during disasters. These initiatives are complicated by fundamental problems of definitions of terms, ambiguity of concepts, lack of standardization in methods of data collection, and inadequate attempts to strengthen the analytic capability of field organizations. Cross-cutting issues in needs assessment, coordination, and evaluation illustrate additional recurring challenges in dealing with evidence in humanitarian assistance. These challenges include lack of agency expertise, dyscoordination at the field level, inappropriate reliance on indicators that measure process rather than outcome, flawed scientific inference, and erosion of the concept of minimum standards. Decision-making in disaster management currently places a premium on expert or eminence-based decisions. By contrast, scientific advances in disaster medicine call for evidence-based decisions whose strength of evidence is established by the methods of data acquisition. At present, disaster relief operations may be data driven, but that does not mean that they are soundly evidence-based. Options for strengthening evidence-based activities include rigorously adhering to evidenced-based interventions, using evidence-based tools to identify new approaches to problems of concern, studying model programs as well as failed ones to identify approaches that deserve replication, and improving standards for evidence of effectiveness in disaster science and services. PMID- 20301065 TI - Health impact of the 2004 Andaman Nicobar earthquake and tsunami in Indonesia. AB - BACKGROUND: The human impact of the tsunami that occurred on 26 December 2004 was enormous, with Indonesia bearing a huge proportion of the losses. The aftermath brought predictions of communicable disease outbreaks and widespread fear of epidemics. However, evidence from previous disasters due to natural hazards does not support all of these predictions. The objectives of this study were to: (1) describe the relative importance of infectious diseases and injuries as a consequence of a disaster due to natural hazards; and (2) identify key recommendations for the improvement of control and surveillance of these diseases during and after disasters. METHODS: A team from the Center for Research on the Epidemiology of Disasters visited Jakarta and Banda Aceh from 11-23 January 2005, and collected data from the Central and Provincial Ministries of Health (MOH), the World Health Organization (WHO), and a field hospital from the International Committee of the Red Cross in Banda Aceh. The epidemiological profiles of diseases before and after the tsunami were compared. Cholera, tetanus, wounds and wound infections, acute respiratory infections, malaria, and dengue were included in this analysis. RESULTS: Certain diseases (e.g., cholera, malaria, dengue) are not always an immediate priority post-disaster. Rates of disaster-related health conditions requiring emergency response fell by half, and became negligible around four weeks after the precipitating events. Some conditions, such as aspiration pneumonia and tetanus, which normally are rare, require special preparedness for emergency personnel. In addition, resistant and rare pathogens are associated with disasters due to natural hazards in the tropics and require specialized knowledge for the rapid and successful treatment of related infections. CONCLUSIONS: Within the first four weeks of a disaster, international humanitarian agencies in the health sector should start working with the MOH. The WHO surveillance system established immediately after the tsunami offers lessons for developing a prototype for future emergencies. Guidelines for tetanus and aspiration pneumonia should be included in disaster medicine handbooks, and humanitarian aid groups should be prepared to provide emergency obstetrics and post-natal services. Relief funding after naturally occurring disasters should consider funding sustainability. Donors should know when to stop providing emergency relief funds and transition to recovery/development strategies. PMID- 20301066 TI - Public health preparedness of post-Katrina and Rita shelter health staff. AB - INTRODUCTION: During 2005, Hurricanes Katrina and Rita struck the US Gulf Coast, displacing approximately two million people. With >250,000 evacuees in shelters, volunteers from the American Red Cross (ARC) and other nongovernmental and faith based organizations provided services. The objective of this study was to evaluate the composition, pre-deployment training, and recognition of scenarios with outbreak potential by shelter health staff. METHODS: A rapid assessment using a 36-item questionnaire was conducted through in-person interviews with shelter health staff immediately following Hurricanes Katrina and Rita. Data were collected by sampling at shelters located throughout five ARC regions in Texas. The survey focused on: (1) public health capacity; (2) level of public health awareness among staff; (3) public health training prior to deployment; and (4) interest in technical support for public health concerns. In addition, health staff volunteers were asked to manage 11 clinical scenarios with possible public health implications. RESULTS: Forty-three health staff at 24 shelters were interviewed. Nurses comprised the majority of shelter health volunteers and were present in 93% of shelters; however, there were no public health providers present as staff in any shelter. Less than one-third of shelter health staff had public health training, and only 55% had received public health information specific to managing the health needs of evacuees. Only 37% of the shelters had a systematic method for screening the healthcare needs of evacuees upon arrival. Although specific clinical scenarios involving case clusters were referred appropriately, 60% of the time, 75% of all clinical scenarios with epidemic potential did not elicit proper notification of public health authorities by shelter health staff. In contrast, clinical scenarios requiring medical attention were correctly referred >90% of the time. Greater access and support from health and public health experts was endorsed by 93% of respondents. CONCLUSIONS: Public health training for sheltering operations must be enhanced and should be a required component of pre-deployment instruction. Development of a standardized shelter intake health screening instrument may facilitate assessment of needs and appropriate resource allocation. Shelter health staff did not recognize or report the majority of cases with epidemic potential to public health authorities. Direct technical support to shelter health staff for public health concerns could bridge existing gaps and assist surveillance efforts. PMID- 20301067 TI - Sheltering the sheltered: protecting the public health and educating the workforce. PMID- 20301068 TI - Evaluation of a pandemic preparedness training intervention of emergency medical services personnel. AB - INTRODUCTION: Emergency medical services (EMS) personnel play an integral role during the national response to a pandemic event. To help ensure their health and safety, especially during the early stages of an outbreak, knowledge and adherence with personal protective equipment (PPE) and infection control strategies will be essential. OBJECTIVES: The objective of this study was to assess the effectiveness of a multi-method, pandemic preparedness training intervention using a pre-/post-test design. METHODS: A convenience sample of 129 EMS personnel participated in a training program on pandemic preparedness. Training consisted of an educational intervention with a focus on the routes of transmission of the influenza virus, proper use of respiratory PPE, agency policies regarding infection control practices, and seasonal influenza vaccination. This was followed by a skill-based drill on respirator fit-checking and proper respirator donning and doffing procedures. RESULTS: Pre-/post-test results indicate a significant increase in knowledge and behavioral intentions with respect to respirator use, vaccination with seasonal influenza vaccine, and willingness to report to duty during a pandemic. CONCLUSIONS: This method was effective in increasing knowledge and compliance intentions in EMS healthcare personnel. Further research should focus on whether training results in behavior modification. PMID- 20301069 TI - Is there an association between risk perception and disaster preparedness in rural US hospitals? AB - INTRODUCTION: This study examined disaster preparedness, risk perception, and their association in rural hospitals in the United States. The focus of disaster preparedness largely has been centered on urban areas, in part because of the perception that more concentrated areas have an increased risk of a disastrous event. Therefore, it was hypothesized that risk perception may be a contributing factor for adequate preparedness in rural areas. This research was a component of a larger study of rural hospital preparedness. The objective of this study was to describe the perceived risk of disaster events and the status of disaster preparedness in rural hospitals. It was hypothesized that there is a positive association between risk perception and preparedness. METHODS: Secondary data analysis was conducted using the National Study of Rural Hospitals (2006-2007) from Johns Hopkins University. The study, based on a regionally stratified, random sample of rural hospitals, consisted of a mailed questionnaire and a follow-up telephone interview with each hospital's Chief Executive Officer (n = 134). A model of disaster preparedness was utilized to examine seven elements of preparedness. Risk perception was examined through seven perceived risk threats. RESULTS: The results indicated that rural hospitals were moderately prepared, overall, (78% prepared on average), with higher preparedness in education/training (89%) and isolation/decontamination (91%); moderate preparedness in administration/planning (80%), communication/notification (83%), staffing/support (66%, and supplies/pharmaceuticals/laboratory support (70%); and lower preparedness in surge capacity (64%). The respondents reported greater perceived risk from disasters due to natural hazards (79% reported moderate to high risk) and vehicular accidents (77%) than from humanmade disasters (23%). Results obtained from logistic regression models indicated that there was no statistically significant difference in the odds of a hospital being prepared overall when comparing high versus low risk perception (OR = 0.61; 95% CI = 0.26 1.44). Positive associations were identified only between higher perceived risk overall and the subcategory of education/training preparedness (OR = 1.24; 95% CI = 1.05-1.27). CONCLUSIONS: Rural hospitals reported being moderately prepared in the event of a disaster with a low perception of risk for human-made disasters. Further research should be conducted to identify predictors of preparedness in rural hospitals in order to optimize readiness for potential disaster events. PMID- 20301070 TI - Moral experience of Canadian healthcare professionals in humanitarian work. AB - INTRODUCTION: Expatriate healthcare professionals frequently participate in international relief operations that are initiated in response to disasters due to natural hazards or humanitarian emergencies in low resource settings. This practice environment is significantly different from the healthcare delivery environment in the home countries of expatriate healthcare professionals. Human rights, public health, medicine, and ethics intersect in distinct ways as healthcare professionals provide care and services in communities affected by crisis. PURPOSE: The purpose of this study was to explore the moral experience of Canadian healthcare professionals during humanitarian relief work. METHODS: This is a qualitative study with 18 semi-structured individual interviews based on Interpretive Description methodology. There are two groups of participants: (1) 15 healthcare professionals (nine doctors, five nurses, and one midwife) with more than three months experience in humanitarian work; and (2) three individuals who have experience as human resource or field coordination officers for humanitarian, non-governmental organizations. Participants were recruited by contacting non-governmental organizations, advertisement at the global health interest group of a national medical society, word of mouth, and a snowball sampling approach in which participants identified healthcare professionals with experience practicing in humanitarian settings who might be interested in the research. RESULTS: Five central themes were identified during the analysis: (1) examination of motivations and expectations; (2) the relational nature of humanitarian work; (3) attending to steep power imbalances; (4) acknowledging and confronting the limits of what is possible in a particular setting; and (5) recognition of how organizational forms and structures shape everyday moral experience. DISCUSSION: Humanitarian relief work is a morally complex activity. Healthcare professionals who participate in humanitarian relief activities, or who are contemplating embarking on a humanitarian project, will benefit from carefully considering the moral dimensions of this work. Humanitarian organizations should address the moral experiences of healthcare professionals in staff recruitment, as they implement training prior to departure, and in supporting healthcare professionals in the field. PMID- 20301071 TI - Personal protection during resuscitation of casualties contaminated with chemical or biological warfare agents--a survey of medical first responders. AB - INTRODUCTION: The threat of mass casualties caused by an unconventional terrorist attack is a challenge for the public health system, with special implications for emergency medicine, anesthesia, and intensive care. Advanced life support of patients injured by chemical or biological warfare agents requires an adequate level of personal protection. The aim of this study was to evaluate the personal protection knowledge of emergency physicians and anesthetists who would be at the frontline of the initial health response to a chemical/biological warfare agent incident. METHODS: After institutional review board approval, knowledge of personal protection measures among emergency medicine (n = 28) and anesthetics (n = 47) specialty registrars in the South Thames Region of the United Kingdom was surveyed using a standardized questionnaire. Participants were asked for the recommended level of personal protection if a chemical/biological warfare agent(s) casualty required advanced life support in the designated hospital resuscitation area. RESULTS: The best awareness within both groups was regarding severe acute respiratory syndrome, and fair knowledge was found regarding anthrax, plague, Ebola, and smallpox. In both groups, knowledge about personal protection requirements against chemical warfare agents was limited. Knowledge about personal protection measures for biological agents was acceptable, but was limited for chemical warfare agents. CONCLUSIONS: The results highlight the need to improve training and education regarding personal protection measures for medical first receivers. PMID- 20301072 TI - Paramedic knowledge, attitudes, and training in end-of-life care. AB - INTRODUCTION: Paramedics often are asked to care for patients at the end of life. To do this, they must communicate effectively with family and caregivers, understand their legal obligations, and know when to withhold unwanted interventions. The objectives of this study were to ascertain paramedics' attitudes toward end-of-life (EOL) situations and the frequency with which they encounter them; and to compare paramedics' preparation during training for a variety of EOL care skills. METHODS: A written survey was administered to a convenience sample of paramedics in two cities: Denver, Colorado and Los Angeles, California. Questions addressed: (1) attitudes toward EOL decision-making in prehospital settings; (2) experience (number of EOL situations experienced in the past two years); (3) importance of various EOL tasks in clinical practice (pronouncing and communicating death, ending resuscitation, honoring advance directives (ADs)); and (4) self-assessed preparation for these EOL tasks. For each task, importance and preparation were measured using a four-point Likert scale. Proportions were compared using McNemar chi-square statistics to identify areas of under- or over-preparation. RESULTS: Two hundred thirty-six paramedics completed the survey. The mean age was 39 years (range 22-59 years), and 222 (94%) were male. Twenty percent had >20 years of experience. Almost all participants (95%; 95% CI = 91-97%) agreed that prehospital providers should honor field ADs, and more than half (59%; 95% CI = 52-65%) felt that providers should honor verbal wishes to limit resuscitation at the scene. Ninety-eight percent of the participants (95% CI = 96-100%) had questioned whether specific life support interventions were appropriate for patients who appeared to have a terminal disease. Twenty-six percent (95% CI = 20-32%) reported to have used their own judgment during the past two years to withhold or end resuscitation in a patient who appeared to have a terminal disease. Significant discrepancies between the importance in practice and the level of preparation during training for the four EOL situations included: (1) understanding ADs (75% very important vs. 40% well prepared; difference 35%: 95% CI = 26-43%); (2) knowing when to honor written ADs (90% very important vs. 59% well-prepared; difference 31%: 95% CI = 23-38%); and (3) verbal ADs (75% very important vs. 54%well-prepared, difference 21%: 95% CI = 12-29%); and (4) communicating death to family or friends (79% very important vs. 48% well prepared, difference 31%: 95% CI = 23 39%). Paramedics' preparation in EOL skills was significantly lower than that for clinical skills such as endotracheal intubation or defibrillation. CONCLUSIONS: There is a need to include more training in EOL care into prehospital training curricula, including how to verify and apply ADs, when to withhold treatments, and how to discuss death with victims' family or friends. PMID- 20301073 TI - The October 2005 earthquake in Northern Pakistan: patterns of injuries in victims brought to the Emergency Relief Hospital, Doraha, Mansehra. AB - OBJECTIVE: Knowledge of injuries of earthquake victims is important to plan relief efforts. This cross-sectional study was conducted following the 08 October 2005 earthquake in Northern Pakistan to determine the pattern of injuries sustained and their relationship with age and gender in order to identify the medical needs in an earthquake-affected zone. METHODS: The study was conducted between 13 October and 23 October 2005 at the Emergency Relief Hospital, Doraha, Mansehra. From the 1,700 patients registered in the hospital, 310 were sampled randomly for the study. Demography and details of the patients' injuries were noted by history and physical examination. Twelve cases were omitted due to incomplete data. RESULTS: Of the cases, 54% were female. Children less than or equal to 10 years old formed the largest age group. Isolated bone injuries were present in 41%, soft tissue injuries in 36%, and mixed injuries in 23% of the patients. The most common bone injury was lower limb fracture (52%), while the most common non-bone injury was non-infected, soft tissue wounds on the limbs (33%). Among patients with soft tissue injuries, gangrenous wounds were present in 9%, and grossly infected wounds in 30% (20% on limbs and 10% on rest of the body). CONCLUSIONS: The population injured during the earthquake showed a higher proportion of females and children less than or equal to 10 years old, and lower limb bone injuries. The data highlight the need to address orthopedic, pediatric, and women's health issues, and for logistic arrangement of relevant diagnostic and therapeutic facilities at the initial stages of relief activities after earthquakes. PMID- 20301074 TI - Editorial comments--October 2005 earthquake in Northern Pakistan: patterns of injuries in victims brought to the Emergency Relief Hospital, Doraha, Mansehra. PMID- 20301075 TI - Disaster relief and recovery after a landslide at a small, rural hospital in Guatemala. AB - INTRODUCTION: Though many reports have assessed hospital emergency responses during a disaster that affected the facility's operations, relatively little work has been dedicated to identifying factors that aid or impede the recovery of such hospitals. PROBLEM: On 05 October 2005, Hurricane Stan triggered landslides that buried an impoverished Mayan community in Santiago Atitlan, Guatemala. The six bed Hospitalito Atitlan also was in the landslide's path. Though opened just months earlier, the institution maintained 24-hour services until reopening in a new facility only 15 days after the landslides. METHODS: This qualitative study examined the Hospitalito Atitlan's disaster recovery using unstructured interviews with key hospital personnel and community members. Participant observation provided information about institutional and cultural dynamics affecting the hospital's recovery. Data were collected retrospectively during June-September 2006 and June 2007. RESULTS: The Hospitalito's emergency responses and recovery were distinct endeavors that nonetheless overlapped in time. The initial 12 hours of disorganized emergency relief work was quickly succeeded by an organized effort by the institution to provide inpatient and clinic-based care to the few severely injured and many worried-well patients. As international aid started arriving 2-3 days post-landslide, the Hospitalito's 24-hour clinical services made it an integral organization in the comprehensive health response. Meanwhile, a subset of the Hospitalito's non-clinical staff initiated rebuilding efforts by Day 2 after the event, joined later by medical staff as outside aid allowed them to hand off clinical duties. Effective use of the Internet and conventional media promoted donations of money and supplies, which provided the raw materials used by a group determined to reopen their hospital. CONCLUSIONS: Early work by a recovery-focused team coupled with a shared understanding of the Hospitalito as an institution that transcended its damaged building drove the hospital's rapid post-emergency revival. Encouraging a similar sense of mission, emulating the Hospitalito's handling of funding and material procurement, and conducting rebuilding and relief efforts in parallel may aid recovery at other health facilities. PMID- 20301076 TI - Large-scale air-medical transport from a peripheral hospital to level-1 trauma centers after remote mass-casualty incidents in Israel. AB - INTRODUCTION: Mass-casualty incidents (MCIs) result in the evacuation of many patients to the nearest medical facility. However, an overwhelming number of patients and the type and severity of injuries may demand rapid, mass airmedical transport to more advanced medical centers. This task may be challenging, particularly after a MCI in a neighboring country. The Israeli Air Force Rescue and Airmedical Evacuation Unit (RAEU) is the main executor of airmedical transport in Israel, including MCIs. PROBLEM: The available data on airmedical transport from remote MCIs are limited.The objective of this study was to evaluate the airmedical transport from a rural hospital after two remote MCIs. METHODS: The study was retrospective and reviewed descriptive records of airmedical transports. RESULTS: The RAEU was involved in airmedical transports from a peripheral hospital shortly after two remote MCIs that occurred in the Sinai desert near the Egyptian-Israeli border. Nineteen (22.4%) and 25 (100%) of the treated trauma patients from each event were airmedically transported to Level-1 Trauma Centers in Israel within hours of the dispatch.The rapid dispatch and accumulation of medical personnel and equipment was remarkable. The airmedical surge capacity was broad and sufficient. Cooperation with local authorities and a tailored boarding procedure facilitated a quality outcome. CONCLUSIONS: The incorporation of a large-scale airmedical transport program with designated multidisciplinary protocols is an essential component to a remote disaster preparedness plan. PMID- 20301077 TI - Establishing disaster medical assistance teams in Japan. AB - INTRODUCTION: The large number casualties caused by the 1995 Great Hanshin and Awaji Earthquake created a massive demand for medical care. However, as area hospitals also were damaged by the earthquake, they were unable to perform their usual functions. Therefore, the care capacity was reduced greatly. Thus, the needs to: (1) transport a large number of injured and ill people out of the disaster-affected area; and (2) dispatch medical teams to perform such wide-area transfers were clear. The need for trained medical teams to provide medical assistance also was made clear after the Niigata-ken Chuetsu Earthquake in 2004. Therefore, the Japanese government decided to establish Disaster Medical Assistance Teams (DMATs), as "mobile, trained medical teams that rapidly can be deployed during the acute phase of a sudden-onset disaster". Disaster Medical Assistance Teams have been established in much of Japan. The provision of emergency relief and medical care and the enhancement and promotion of DMATs for wide-area deployments during disasters were incorporated formally in the Basic Plan for Disaster Prevention in its July 2005 amendment. RESULTS: The essential points pertaining to DMATs were summarized as a set of guidelines for DMAT deployment. These were based on the results of research funded by a Health and Labour Sciences research grant from the, Labour and Welfare (MHLW) of the Ministry of Health. The guidelines define the basic procedures for DMAT activities-for example: (1) the activities are to be based on agreements concluded between prefectures and medical institutions during non-emergency times; and (2) deployment is based on requests from disaster-affected prefectures and the basic roles of prefectures and the MHLW. The guidelines also detail DMAT activities at the disaster scene of the, support from medical institutions, and transportation assistance including "wide-area" medical transport activities, such as medical treatment in staging care units and the implementation of medical treatment onboard aircraft. CONCLUSIONS: Japan's DMATs are small-scale units that are designed to be suitable for responding to the demands of acute emergencies. Further issues to be examined in relation to DMATs include expanding their application to all prefectures, and systems to facilitate continuous education and training. PMID- 20301078 TI - A fundamental, national, medical disaster management plan: an education-based model. AB - During disasters, especially following earthquakes, health systems are expected to play an essential role in reducing mortality and morbidity. The most significant naturally occurring disaster in Iran is earthquakes; they have killed >180,000 people in the last 90 years. According to the current plan in 2007, the disaster management system of Iran is composed of three main work groups: (1) Prevention and risk management, (2) Education, and (3) Operation. This organizational separation has resulted in lack of necessary training programs for experts of specialized organizations, e.g., the Ministry of Health and Medical Education (MOHME).The National Board of MOHME arranged a training program in the field of medical disaster management. A qualified training team was chosen to conduct this program in each collaborating center, based on a predefined schedule. All collaborating centers were asked to recall 5-7 experts from each member university. Working in medical disaster management field for greater than or equal to 2 years was an inclusion criterion. The training programs lasted three days, consisted of all relevant aspects of medical disaster management, and were conducted over a six-month period (November 2007-April 2008). Pre-test and post-tests were used to examine the participants' knowledge regarding disaster management; the mean score on the pretest was 67.1 +/-11.6 and 88.1 +/-6.2, respectively. All participants were asked to hold the same training course for their organizations in order to enhance knowledge of related managers, stakeholders, and workers, and build capacity at the local and provincial levels. The next step was supposed to be developing a comprehensive medical disaster management plan for the entire country. Establishing nine disaster management regional collaborating centers in the health system of Iran has provided an appropriate base for related programs to be rapidly and easily accomplished throughout the country. This tree-shaped model is recommended as a cost-benefit and rapid approach for conducting training programs and developing a disaster management plan in the health system of a developing country. PMID- 20301079 TI - Just-in-time public health training and networking in Farsi-speaking countries: Influenza A (H1N1) experience. PMID- 20301080 TI - Genomic damage in endothelial progenitor cells from uremic patients in hemodialysis. AB - INTRODUCTION: End stage renal disease (ESRD) is associated with a high incidence of cardiovascular disease and cancer. Patients undergoing hemodialysis show a reduced number and an impaired function of endothelial progenitor cells (EPCs), which in physiological conditions contribute to repair the vascular damage. In patients with ESRD, massive oxidative genome damage has been demonstrated but the role of HD in causing it is still a controversial issue. The aim of our study was to analyze the effects of a single HD session on the number of cells marked with CD34 (including sub-type cells known to be EPCs); we then evaluated the genomic damage in these cells using COMET assay. PATIENTS AND METHODS: We quantified CD34(+) cells in blood samples in 30 patients in hemodiafiltration treatment for 3.5 to 4 hours 3 times/week and in 30 healthy volunteers. In HD patients, blood samples were drawn at different time intervals: start of dialysis (T(0)), at the end of the treatment (T(end)) and 24 hours afterwards in the interdialytic day (T(inter)). Staining and analysis was performed using the ISHAGE (International Society of Hematotherapy and Graft Engineering) guidelines. EPCs count was conducted using a multiparameter flow cytometric lyse no-wash method. Genomic damage was evaluated by Comet assay. RESULTS: The number of CD34(+) cells in the HD patients at the beginning of the dialysis session (T(0)) was significantly lower than in healthy controls. HD patients showed a significant increase in CD34 number at the end of the session (T(end)) with respect to T(0). In the interdialytic period (T(int)), the number of CD34(+) cells was significantly reduced with respect to T(end). COMET assay performed on CD34(+) cells showed a higher basal level of genomic damage in HD patients than in controls; it increased in a statistically significant manner after the hemodialysis session, while in the interdialytic period it came back to T(0) level. CONCLUSIONS: Uremic status is characterized by lower levels of circulating EPCs, which increase after a single session of HD together with genomic damage to the CD34(+) cells. PMID- 20301081 TI - The effects of vitamin E-coated dialysis membranes on serum paraoxonase activity in hemodialysis patients. AB - BACKGROUND: Hemodialysis patients are exposed to oxidative stress, which can lead to several complications. We therefore sought to evaluate the effect of using vitamin E-coated dialysis membranes for a period of 3 months on serum paraoxonase activity and oxidative stress markers. METHODS: Twenty patients and 25 healthy controls were included in this study. Hemodialysis patients were evaluated before and after 3 months of treatment with vitamin E-coated dialysis membranes. Plasma malondialdehyde (MDA) levels, as well as the oxidizability of red blood cells (RBCs) and apolipoprotein B-containing lipoproteins (expressed as RBC-MDA and DeltaMDA, respectively) were determined in order to investigate the patients' oxidative status. Plasma vitamin E and vitamin C levels, serum total carotenoid levels and paraoxonase activity were measured to investigate the patients' antioxidative defenses. RESULTS: After 3 months of treatment with vitamin E coated membranes, vitamin E levels were significantly increased and the oxidizability of RBCs was significantly reduced in the hemodialysis patients. However, there were not any differences from baseline in serum paraoxonase activity, plasma MDA levels or the oxidizability of apolipoprotein B-containing lipoproteins in these patients. CONCLUSIONS: Despite promising improvements in vitamin E levels and the oxidizability of RBCs, the results of this study do not support a satisfactory antioxidative effect of vitamin E-coated dialysis membranes. Further studies are needed to identify antioxidative treatments for hemodialysis patients. PMID- 20301082 TI - Severe reversible acute renal failure in idiopathic nephrotic syndrome. AB - BACKGROUND: Only few cases of acute renal failure (ARF) requiring dialysis have been reported in patients with idiopathic nephrotic syndrome (NS). This study aims to better define the clinical outcome and treatment of this condition. METHODS: A pilot enquiry regarding the occurrence of ARF requiring dialysis in patients with NS and biopsy proven minimal changes (MC) or focal segmental glomerulosclerosis (FSGS) was conducted among 5 nephrology centers. RESULTS: From 1996-2006, 6 patients with idiopathic NS (4 MC, 2 FSGS) developed ARF requiring dialysis early after onset of NS. At presentation all but 1 patient had elevated blood pressure. Patients were treated with dialysis from 7-40 days. All achieved complete or partial remission after 4-8 weeks of steroids. Recovery of renal function paralleled with the reduction of proteinuria. At renal biopsy proximal tubules showed a large amount of protein droplets, flattening of epithelial cells, and focal detachment of cells from the basal membrane. After a follow-up of 24-60 months, 5 patients had a relapse. Of these 4 were responsive to steroids, while one progressed to dialysis after an episode of hemolytic uremic syndrome related to cyclosporine treatment. ARF did not recur. CONCLUSION: ARF requiring dialysis is a rare and unexpected complication of idiopathic NS occurring in most cases early after presentation. These patients are sensitive to steroids that should be administered as promptly as possible in view of the potential noxious effect of protein overload on proximal tubular cells. PMID- 20301083 TI - Serum parathyroid hormone and phosphate influence the levels of circulating CD34+ cells in uremia. AB - BACKGROUND: Parathyroid hormone (PTH) is an active stimulator of bone marrow osteoblasts; it is involved in the niche organization, ie the bone marrow microenvironment which controls the turnover and the fate of endothelial progenitor cells (EPCs). PTH stimulates EPC production; this action can be measured by counting the number of circulating CD34+ cells. METHODS: This observational cross-sectional study aimed to verify this effect in 3 groups of hemodialysis patients with different serum PTH levels. The first group consisted of 11 patients affected by secondary hyperparathyroidism (SHPTH group, serum PTH levels >500 pg/ml); the second group consisted of 10 patients with serum PTH levels between 150 and 500 pg/ml (TargetPTH group); the third group consisted of 10 patients with serum PTH levels below the treatment target after parathyroidectomy (PTx group, serum PTH levels <150 pg/ml). Serum PTH, calcium (Ca), phosphorus (P), alkaline phosphatases (ALP), urea nitrogen, albumin and hemoglobin were measured. Flow cytofluorimetry with CD45+ sequential gating was effected; therefore, CD34+ cells could be analyzed. RESULTS: The SHPTH group showed significantly higher values of serum PTH, P and ALP (respectively, p<0.0001, p<0.033 and p<0.0001), and significantly lower values of circulating CD34+ cells (both in absolute and percent terms) in the SHPTH and in the TargetPTH groups (for both, p<0.0001). Two models of multiple regression analysis built with circulating CD34+ cells (expressed as percentage in the first one and as absolute values in the second one) as dependent variables showed that only serum PTH and P values were inversely associated with both. CONCLUSIONS: Our data suggest that an inverse relationship exists in uremic patients among circulating CD34+ cells and serum P and PTH levels. The count of circulating CD34+ cells might represent a novel biomarker for the assessment of the cardiovascular risk for dialysis patients. PMID- 20301084 TI - Do statins delay the incidence of ESRD in diabetic patients with moderate CKD? AB - BACKGROUND: There is little information on whether statins and LDL cholesterol are associated with the onset of end-stage renal disease (ESRD) in at-risk populations. METHODS: In a retrospective, single-center study of 156 patients with diabetes and CKD, we evaluated disease progression and incidence of ESRD in patients treated or not treated with statins. RESULTS: There were 81 and 75 patients in statin and no-statin groups respectively. Participants were followed for a median of 28 months (95% CI 19 to 34). Total cholesterol and LDL levels decreased significantly in the statin group and were associated with a significant decrease in the rate of eGFR decline (-6.0 vs. -9.8 mL/min/1.73m(2)/year, p=0.01). However, this difference was not statistically significant after consideration of propensity scores (p=0.43). Kaplan-Meier survival analyses demonstrated that the incidence of ESRD was significantly greater in the no-treatment group (HR=2.21, 95% CI 1.45-3.81, p=0.0007). LDL cholesterol, statins, eGFR, mean arterial pressure and ACE-I/ARB were significant predictors of ESRD in univariate analyses. However, stepwise Cox regression analyses using propensity scores only retained LDL and baseline eGFR as independent predictors of ESRD. CONCLUSIONS: Only LDL cholesterol but not statins were associated with ESRD progression in diabetic patients with moderate CKD after data adjustment for propensity scores. Prospective studies are needed to determine if LDL cholesterol mediates the effect of statins on disease progression in these patients. PMID- 20301085 TI - Pedometers as a means to increase spontaneous physical activity in chronic hemodialysis patients. AB - BACKGROUND: Pedometers are simple devices which measure spontaneous physical activity. In nonrenal disease populations, pedometers were successfully used to encourage patients to increase their habitual physical activity through self monitoring of its intensity. Our aim was to investigate how an awareness of using pedometers helps in increasing daily spontaneous physical activity in patients on hemodialysis. METHODS: We studied 33 hemodialysis patients (16 women, 17 men; mean age 58.3 +/- 10.1 years; mean dialysis vintage 41.4 +/- 28.6 months). Daily walking activity was measured by pedometers 7 times over 4 months during 5 midweek interdialysis periods and 2 dialysis-free weekends. During the study, patients recorded their activities and pedometer readings. Blood count, serum albumin, electrolytes, lipids, C-reactive protein (CRP), interdialytic weight gain and erythropoiesis-stimulating agent dosages were also measured. Body composition was estimated with multifrequency phase-sensitive bioimpedance. The patients also filled in the SF-36 questionnaire. RESULTS: Total number of steps counted between 2 midweek dialysis sessions increased from a mean 9,337 +/- 5,317 to 11,921 +/- 5,909 (p=0.001). Number of steps during dialysis-free days increased, from 3,766 +/- 1,963 to 4,978 +/- 2,495 (p=0.0005). Total number of steps between midweek dialysis and dialysis after dialysis-free weekend break tended to increase from 20,974 +/- 10,696 to 22,080 +/- 11,631 (p=0.06). At study end, the number of steps taken during weekend days was greater than during between midweek dialysis sessions. Bioimpedance did not reveal significant changes of body composition. The patients had similar scores on physical functioning, general health and mental health perception and total SF-36 at the end of the study. CONCLUSION: Pedometers could serve as a simple means to increase spontaneous physical activity in patients on chronic hemodialysis. PMID- 20301086 TI - Evaluation of visual evoked potentials in chronic renal failure patients with different treatment modalities. AB - BACKGROUND: Uremia causes central nervous system (CNS) dysfunction. Modern diagnostic methods are useful for the recognition of CNS complications in uremic patients. Data concerning visual evoked potentials (VEPs) of chronic renal failure (CRF) patients is limited. OBJECTIVE: In this study, we aimed to assess and compare VEPs abnormalities in CRF patients managed by only medical therapy (pre-dialysis) or medical therapy plus renal replacement therapy (continuous ambulatory peritoneal dialysis (CAPD) or hemodialysis (HD)). MATERIALS AND METHODS: Fifty-nine patients diagnosed with CRF of various etiologies were divided into 3 groups according to the treatment modalities used to manage CRF; pre-dialysis group, HD group and CAPD group. For the comparison of VEPs parameters, an age matched control group was formed with 10 healthy subjects. RESULTS: Bilateral N2 latency (p<0.001), bilateral P2 latency (p=0.003), right N2 latency (p=0.006) and left VEP N2 latency (p=0.002) in the HD group was significantly higher than the control group. The CAPD group had significantly increased bilateral N2 latency (p<0.001), right eye VEP N2 latency (p=0.004), right eye P2 latency (p=0.001), left eye N2 latency (p=0.005) and left eye P2 latency (p=0.001) levels than the control group. There was no significant difference between VEPs of the CAPD and HD groups. CONCLUSION: The renal replacement treatments that we evaluated have similar effects on VEPs. Diminished VEPs indicating visual neuronal system damage were observed, when CRF progresses. CNS dysfunctions can be diagnosed and additional therapeutic approaches could be followed using VEPs during the treatment of CRF. PMID- 20301087 TI - Qualitative screening for volatile organic compounds in human blood using solid phase microextraction and gas chromatography-mass spectrometry. AB - A fast and simple screening procedure using solid-phase microextraction and gas chromatography-mass spectrometry (SPME-GC-MS) in full-scan mode for the determination of volatile organic compounds (VOC) is presented. The development of a fast and simple screening technique for the simultaneous determination of various volatiles is of great importance, because of their widespread use, frequent occurrence in forensic toxicological questions and the fact that there is often no hint on involved substances at the crime scene. To simulate a screening procedure, eight VOC with different chemical characteristics were chosen (isoflurane, halothane, hexane, chloroform, benzene, isooctane, toluene and xylene). To achieve maximum sensitivity, variables that influence the SPME process, such as type of fiber, extraction and desorption temperature and time, agitation and additives were optimized by preliminary studies and by means of a central composite design. The limits of detection and recoveries ranged from 2.9 microg/l (xylene) to 37.1 microg/l (isoflurane) and 7.9% (chloroform) to 61.5% (benzene), respectively. This procedure can be used to answer various forensic and toxicological questions. The short time taken for the whole analytical procedure may make its eventual adoption for routine analysis attractive. PMID- 20301088 TI - Structural identification of hindered amine light stabilisers in coil coatings using electrospray ionisation tandem mass spectrometry. AB - Hindered amine light stabilisers (HALS) are the most effective antioxidants currently available for polymer systems in post-production, in-service applications, yet the mechanism of their action is still not fully understood. Structural characterisation of HALS in polymer matrices, particularly the identification of structural modifications brought about by oxidative conditions, is critical to aid mechanistic understanding of the prophylactic effects of these molecules. In this work, electrospray ionisation tandem mass spectrometry (ESI MS/MS) was applied to the analysis of a suite of commercially available 2,2,6,6 tetramethylpiperidine-based HALS. Fragmentation mechanisms for the [M + H](+) ions are proposed, which provide a rationale for the product ions observed in the MS/MS and MS(3) mass spectra of N-H, N-CH(3), N-C(O)CH(3) and N-OR containing HALS (where R is an alkyl substituent). A common product ion at m/z 123 was identified for the group of antioxidants containing N-H, N-CH(3) or N-C(O)CH(3) functionality, and this product ion was employed in precursor ion scans on a triple quadrupole mass spectrometer to identify the HALS species present in a crude extract from of a polyester-based coil coating. Using MS/MS, two degradation products were unambiguously identified. This technique provides a simple and selective approach to monitoring HALS structures within complex matrices. PMID- 20301089 TI - Treating the aged in rural communities: the application of cognitive-behavioral therapy for depression. AB - Many rural communities are experiencing an increase in their older adult population. Older adults who live in rural areas typically have fewer resources and poorer mental and physical health status than do their urban counterparts. Depression is the most prevalent mental health problem among older adults, and 80% of the cases are treatable. Unfortunately, for many rural elders, depressive disorders are widely under-recognized and often untreated or undertreated. Psychotherapy is illustrated with the case of a 65-year-old rural married man whose presenting complaint was depressive symptoms after a myocardial infarction and loss of ability to work. The case illustrates that respect for rural elderly clients' deeply held beliefs about gender and therapy, coupled with an understanding of their limited resources, can be combined with psychoeducational and therapeutic interventions to offer new options. PMID- 20301090 TI - Synthesis, 1H and 13C NMR assignment and electrochemical properties of novel thiophene-thiazolothiazole oligomers and polymers. AB - Novel hexyl-substituted bisthiophene compounds containing a thiazolothiazole(5,4 d) unit have been explored. The molecules are soluble in common organic solvents, which would enhance their chance of possible integration in printable electronics. Synthesis and complete elucidation of the chemical structures by detailed 1D/2D NMR spectroscopy are described. This provides interesting input for chemical shift prediction software, because few experimental data on this type of compounds are available. Furthermore, the potential n-type character of these derivatives is verified using electrochemical measurements. In addition, the low-bandgap character of conjugated polymers containing the thiazolothiazole unit is demonstrated by performing an electropolymerization. PMID- 20301091 TI - Quantification, confirmation and screening capability of UHPLC coupled to triple quadrupole and hybrid quadrupole time-of-flight mass spectrometry in pesticide residue analysis. AB - The potential of three mass spectrometry (MS) analyzers (triple quadrupole, QqQ; time of flight, TOF; and quadrupole time of flight, QTOF) has been investigated and compared for quantification, confirmation and screening purposes in pesticide residue analysis of fruit and vegetable samples. For this purpose, analytical methodology for multiresidue determination of 11 pesticides, taken as a model, has been developed and validated in nine food matrices for the three mass analyzers coupled to ultra high pressure liquid chromatography. In all cases, limits of quantification around 0.01 mg/kg were reached, fulfilling the most restrictive case of baby-food analysis. Regarding absolute sensitivity, the lower limits of detection were obtained, as expected, for QqQ (100 fg), whereas slightly higher limits (300 fg) were obtained for both TOF and QTOF. Confirmative capacity of each analyzer was studied for each analyte based on the identification points (IPs) criterion, useful for a comprehensive comparison. QTOF mass analyzer showed the highest confirmatory capacity, although QqQ normally led to sufficient number of IPs, even at lower concentration levels. The potential of TOF MS was also investigated for screening purposes. To this aim, around 50 commercial fruits and vegetables samples were analyzed, searching for more than 400 pesticides. TOF MS proved to be an attractive analytical tool for rapid detection and reliable identification of a large number of pesticides thanks to the full spectrum acquisition at accurate mass with satisfactory sensitivity. This process is readily boosted when combined with specialized software packages, together with theoretical exact mass databases. Several pesticides (e.g. carbendazim in citrus and indoxacarb in grape) were detected in the samples. Further unequivocal confirmation of the identity was performed using reference standards and/or QTOF MS/MS experiments. PMID- 20301092 TI - On the use of a dual-scale model to improve understanding of a pharmaceutical freeze-drying process. AB - The evolution of product temperature and of residual ice content in the various vials of a batch during a freeze-drying process can be significantly affected by local conditions around each vial. In fact, vapor fluid dynamics in the drying chamber determines the local pressure that, taking into account the heat flow from the shelf and, eventually, radiation from chamber surfaces, is responsible for the sublimation rate and product temperature. These issues have to be taken into account when using mathematical simulation to predict the evolution of the product as a consequence of the operating conditions (recipe design), as well as during the scale-up of a recipe obtained in a small-scale equipment to a large scale unit. In this framework, a dual-scale model can significantly improve the understanding for pharmaceuticals freeze-drying processes: it couples a three dimensional model, describing the fluid dynamics in the chamber, and a second mathematical model, either mono- or bi-dimensional, describing the drying of the product in each vial. Thus, it can be profitably used to gain knowledge about process dynamics, and to improve the design of the equipment, as well as the performance of the control system of the process. PMID- 20301093 TI - 1H and 13C NMR spectral data of bioactive cage-like polycyclic compounds. AB - Bioactive cage-like polycyclic compounds have attracted the attention of several research groups because of their unique appearance and their biological activities. Their structures were established on the basis of (1)H NMR and (13)C NMR spectroscopic data. The (1)H and (13)C signal assignments and most homonuclear hydrogen coupling constants were assigned by use of techniques such as 1D (1)H and (13)C NMR and 2D gCOSY, non-edited gHSQC and gHMBC. The gNOESY experiments proved the endo-stereochemistry. PMID- 20301094 TI - There is a steady-state transcriptome in exponentially growing yeast cells. AB - The growth of yeast cells in batches in glucose-based media is a standard condition in most yeast laboratories. Most gene expression experiments are done by taking this condition as a reference. Presumably, cells are in a stable physiological condition that can be easily reproduced in other laboratories. With this assumption, however, it is necessary to consider that the average amount of the mRNAs per cell for most genes does not change during exponential growth. That is to say, there is a steady-state condition for the transcriptome. However, this has not been rigorously demonstrated to date. In this work we take several cell samples during the exponential phase growth to perform a kinetic study using the genomic run-on (GRO) technique, which allows simultaneous measurement of the amount of mRNA and transcription rate variation at the genomic level. We show here that the steady-state condition is fulfilled for almost all the genes during most exponential growth in yeast extract-peptone-dextrose medium (YPD) and, therefore, that simultaneous measures of the transcription rates and the amounts of mRNA can be used for indirect mRNA stability calculations. With this kinetic approach, we were also able to determine the relative influence of the transcription rate and the mRNA stability changes for the mRNA variation for those genes that deviate from the steady state. PMID- 20301095 TI - Novel graph distance matrix. AB - We have introduced novel distance matrix for graphs, which is based on interpretation of columns of the adjacency matrix of a graph as a set of points in n-dimensional space, n being the number of vertices in the graph. Numerical values for the distances are based on the Euclidean distance between n points in n-dimensional space. In this way, we have combined the traditional representation of graphs (drawn as 2D object of no fixed geometry) with their representation in n-dimensional space, defined by a set of n-points that lead to a representation of definite geometry. The novel distance matrix, referred to as natural distance matrix, shows some structural properties and offers novel graph invariants as molecular descriptors for structure-property-activity studies. One of the novel graph descriptors is the modified connectivity index in which the bond contribution for (m, n) bond-type is given by 1/ radical(m + n), where m and n are the valence of the end vertices of the bond. The novel distance matrix (ND) can be reduced to sparse distance-adjacency matrix (DA), which can be viewed as specially weighted adjacency matrix of a graph. The quotient of the leading eigenvalues of novel distance-adjacency matrix and novel distance matrix, as illustrated on a collection of graphs of chemical interest, show parallelism with a simple measure of graph density, based on the quotient of the number of edges in a graph and the maximal possible number of edges for graphs of the same size. PMID- 20301096 TI - Making the diagnosis with only two levels of nongynecologic cell blocks as opposed to three is more cost effective. AB - Two hundred forty-three of 246 cases in phase I (98.8%) and 246 of 247 cases in phase II (99.6%) had adequate or the same material present on the level two cell blocks. Sixty-nine cases were malignant (28.1%), 20 were atypical (8.1%), 157 were benign (63.8), and 16 were signed out on the cell block only (6.5%) in phase I. In phase II, 69 (27.9%) cases were malignant, 22 (8.9%) were atypical, 156 (63.2%) were benign, and 18 (7.3%) were signed out based on material present in the cell block. Fifteen cases in phase I (6.1%) and 17 (6.9%) in phase II needed immunohistochemical staining for further evaluation. Twenty-four upper urinary tract (UUT) cases were signed out as malignant (49.0%), 10 were atypical (20.4%), and 15 were benign (30.6%) in phase I. In phase II, 18 (56.3%) UUT were malignant, 8 (25.0%) were atypical, and 6 (18.7%) were benign. In phase I, 13 (26.5%) and in phase II, 18 (56.3%) were graded on the cell block only. On comparing the two phases, there was no significant difference in the amount of diagnostic material present between the level three and level two cell blocks (98.8% and 99.6%, respectively) or the number of cases diagnosed based on the cell block (6.5% and 7.3%, respectively). Cases signed out as malignant, atypical, and benign were similar in both phases. Likewise, the cases that required immunohistochemical staining to aid in the diagnosis between phase one and phase two were similar (6.1% and 6.9%, respectively). respectively). PMID- 20301097 TI - Generation of functional hepatocytes from human embryonic stem cells under chemically defined conditions that recapitulate liver development. AB - Generation of hepatocytes from human embryonic stem cells (hESCs) could represent an advantageous source of cells for cell therapy approaches as an alternative to orthotopic liver transplantation. However, the generation of differentiated hepatocytes from hESCs remains a major challenge, especially using a method compatible with clinical applications. We report a novel approach to differentiate hESCs into functional hepatic cells using fully defined culture conditions, which recapitulate essential stages of liver development. hESCs were first differentiated into a homogenous population of endoderm cells using a combination of activin, fibroblast growth factor 2, and bone morphogenetic protein 4 together with phosphoinositide 3-kinase inhibition. The endoderm cells were then induced to differentiate further into hepatic progenitors using fibroblast growth factor 10, retinoic acid, and an inhibitor of activin/nodal receptor. After further maturation, these cells expressed markers of mature hepatocytes, including asialoglycoprotein receptor, tyrosine aminotransferase, alpha1-antitrypsin, Cyp7A1, and hepatic transcription factors such as hepatocyte nuclear factors 4alpha and 6. Furthermore, the cells generated under these conditions exhibited hepatic functions in vitro, including glycogen storage, cytochrome activity, and low-density lipoprotein uptake. After transduction with a green fluorescent protein-expressing lentivector and transplantation into immunodeficient uPA transgenic mice, differentiated cells engrafted into the liver, grew, and expressed human albumin and alpha1-antitrypsin as well as green fluorescent protein for at least 8 weeks. In addition, we showed that hepatic cells could be generated from human-induced pluripotent cells derived from reprogrammed fibroblasts, demonstrating the efficacy of this approach with pluripotent stem cells of diverse origins. CONCLUSION: We have developed a robust and efficient method to differentiate pluripotent stem cells into hepatic cells, which exhibit characteristics of human hepatocytes. Our approach should facilitate the development of clinical grade hepatocytes for transplantation and for research on drug discovery. PMID- 20301099 TI - Gas-fragmentation study of the novel synthetic zwitterionic drug 3-methyl-9-(2 oxa-2lambda5-2H-1,3,2-oxazaphosphorine-2-cyclohexyl)-3,6,9 triazaspiro[5,5]undecane chloride (SLXM-2) by electrospray ionization tandem mass spectrometry. AB - The zwitterionic drug 3-methyl-9-(2-oxa-2lambda5-2H-1,3,2-oxazaphosphorine-2 cyclohexyl)-3,6,9-triazaspiro[5,5]undecane chloride (SLXM-2) is a novel synthetic compound which has shown anticancer activity and low toxicity in vivo. In this study, the various gas-phase fragmentation routes were analyzed by electrospray ionization mass spectrometry (positive ion mode) in conjunction with tandem mass spectrometry (ESI-MS(n)) for the first time. In ESI-MS the fragment ion at m/z 289 (base peak) was formed by loss of the chlorine anion from the zwitterionic precursor SLXM-2. The fragment ion at m/z 232 was formed from the ion at m/z 289 by loss of 1-methylaziridine. The detailed gas-phase collision-induced dissociation (CID) fragmentation mechanisms obtained from the various precursor ions extracted from the zwitterionic SLXM-2 drug was obtained by tandem mass spectrometry analyses. PMID- 20301100 TI - Release kinetics of actives from chewing gums into saliva monitored by direct analysis in real time mass spectrometry. AB - Direct analysis in real time mass spectrometry (DART-MS) was used to monitor the release kinetics of a taste-refreshing compound from chewing gums into the saliva of subjects. A new DART-MS sample probe was designed which was about four times more sensitive than the current benchmark probe. This decreased the impact of the dilution of the saliva samples that was required to minimize ion suppression effects and make quantitative analyses without an internal standard possible. The new probe was also about three times more reproducible, which allowed quantitative measurements to be conducted manually without requiring the enhanced precision provided by an automatic sample positioner. The accuracy of analyses performed by DART-MS was verified by comparing the results obtained from saliva samples analyzed both by DART-MS and by a more classical liquid chromatography/mass spectrometry (LC/MS) method. This investigation showed good agreement between the two techniques. DART-MS could then be used to objectively demonstrate the efficiency of a granular carbohydrate-based delivery system to boost for a few minutes the release of a lipophilic flavor raw material with a high octanol/water partition coefficient, cyclohexanecarboxamide, N-ethyl-5 methyl-2-(1-methylethyl) (WS-3), from chewing gum into saliva. PMID- 20301101 TI - Direct quantification of 11-nor-Delta(9)-tetrahydrocannabinol-9-carboxylic acid in urine by liquid chromatography/tandem mass spectrometry in relation to doping control analysis. AB - An accurate and precise method for the quantification of 11-nor-Delta(9) tetrahydrocannabinol-9-carboxylic acid (THCA) in urine by liquid chromatography/tandem mass spectrometry (LC/MS/MS) for doping analysis purposes has been developed. The method involves the use of only 200 microL of urine and the use of D(9)-THCA as internal standard. No extraction procedure is used. The urine samples are hydrolysed using sodium hydroxide and diluted with a mixture of methanol/glacial acetic acid (1:1). Chromatographic separation is achieved using a C8 column with gradient elution. All MS and MS/MS parameters were optimised in both positive and negative electrospray ionisation modes. For the identification and the quantification of THCA three product ions are monitored in both ionisation modes. The method is linear over the studied range (5-40 ng/mL), with satisfactory intra-and inter-assay precision, and the relative standard deviations (RSDs) are lower than 15%. Good accuracy is achieved with bias less than 10% at all levels tested. No significant matrix effects are observed. The selectivity and specificity are satisfactory, and no interferences are detected. The LC/MS/MS method was applied for the analysis of 48 real urine samples previously analysed with a routine gas chromatography/mass spectrometry (GC/MS) method. A good correlation between the two methods was obtained (r(2) > 0.98) with a slope close to 1. PMID- 20301102 TI - Stable ion complexes of vitamin A species (retinol) in solution as detected by mass spectrometry. AB - Mechanisms of retinol (ROL) transport in plasma alternative to that involving the Retinol-Binding Protein (RBP) have been hypothesized after RBP-knockout mice were shown to be viable and fertile. Accordingly, the possibility of a ROL fraction circulating free in plasma has been suggested. In this study, stable complex formation between ROL and the physiological relevant ions Na(+), Li(+), and K(+) was investigated by using mass spectrometry and assessed in regard to the aforementioned alternative mechanism. The ROL-Na complex was found to be kinetically favoured with respect to the ROL-Li and ROL-K complexes. Fragmentation of the [ROL-Na](+) adduct rendered the carbocation [ROL+H-H(2)O](+) (m/z 269) and NaOH as neutral loss. In consonance with these results, it is hypothesized on the possibility of the complex [ROL-Na](+) being an alternative way of ROL transport to cells, as well as an intermediate in cis/trans isomerism. PMID- 20301103 TI - Analysis of benzofuran derivatives using electrospray ionization ion trap and electrospray ionization quadrupole time-of-flight mass spectrometry. PMID- 20301104 TI - Surface-activated chemical ionization time-of-flight mass spectrometry and labeling-free approach: two powerful tools for the analysis of complex plant functional proteome profiles. AB - Surface-activated chemical ionization (SACI) has been widely used in recent years to analyze a range of different compounds (e.g., peptides, street drugs, amino acids). The main benefits of this technology are its high sensitivity and its effectiveness under different chromatographic conditions. Here, we used SACI in conjunction with a highly selective quadrupole time-of-flight mass analyzer to characterize a complex proteome pattern after separation by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). The data obtained were compared with those obtained using the micro-electrospray ionization (ESI) approach, which showed that using SACI strongly increased the number of detectable proteins. The higher sensitivity is mainly due to the ability of SACI to selectively produce singly charged species of high intensity under full-scan conditions and doubly charged species for tandem mass spectrometric (MS/MS) peptide characterization by simply changing the ionization conditions during data acquisition. PMID- 20301105 TI - Comprehensive plasma-screening for known and unknown substances in doping controls. AB - Occasionally, doping analysis has been recognized as a competitive challenge between cheating sportsmen and the analytical capabilities of testing laboratories. Both have made immense progress during the last decades, but obviously the athletes have the questionable benefit of frequently being able to switch to new, unknown and untested compounds to enhance their performance. Thus, as analytical counteraction and for effective drug testing, a complementary approach to classical targeted methods is required in order to implement a comprehensive screening procedure for known and unknown xenobiotics. The present study provides a new analytical strategy to circumvent the targeted character of classical doping controls without losing the required sensitivity and specificity. Using 50 microL of plasma only, the method potentially identifies illicit drugs in low ng/mL concentrations. Plasma provides the biological fluid with the circulating, unmodified xenobiotics; thus the identification of unknown compounds is facilitated. After a simple protein precipitation, liquid chromatographic separation and subsequent detection by means of high resolution/high accuracy orbitrap mass spectrometry, the procedure enables the determination of numerous compounds from different classes prohibited by the World Anti-Doping Agency (WADA). A new hyphenated mass spectrometry technology was employed without precursor ion selection for higher collision energy dissociation (HCD) fragmentation experiments. Thus the mass spectra contained all the desired information to identify unknown substances retrospectively. The method was validated for 32 selected model compounds for qualitative purposes considering the parameters specificity, selectivity, limit of detection (<0.1-10 ng/mL), precision (9-28%), robustness, linearity, ion suppression and recovery (80-112%). In addition to the identification of unknown compounds, the plasma samples were simultaneously screened for known prohibited targets. PMID- 20301106 TI - In situ probing of cholesterol in astrocytes at the single-cell level using laser desorption ionization mass spectrometric imaging with colloidal silver. AB - Mass spectrometric imaging has been utilized to localize individual astrocytes and to obtain cholesterol populations at the single-cell level in laser desorption ionization (LDI) with colloidal silver. The silver ion adduct of membrane-bound cholesterol was monitored to detect individual cells. Good correlation between mass spectrometric and optical images at different cell densities indicates the ability to perform single-cell studies of cholesterol abundance. The feasibility of quantification is confirmed by the agreement between the LDI-MS ion signals and the results from a traditional enzymatic fluorometric assay. We propose that this approach could be an effective tool to study chemical populations at the cellular level. PMID- 20301107 TI - High-throughput analysis of in vitro cytochrome p450 inhibition samples using mass spectrometry coupled with an integrated liquid chromatography/autosampler system. PMID- 20301108 TI - Production and isolation of ligated metal(IV)-oxo ions by tandem mass spectrometry. AB - High valent metal(IV)-oxo species, [M(==O)(MeIm)(n)(OAc)](+) (M = Mn-Ni, MeIm = 1 methylimidazole, n = 1-2), which are relevant to biology and oxidative catalysis, were produced and isolated in gas-phase reactions of the metal(II) precursor ions [M(MeIm)(n)(OAc)](+) (M = Mn-Zn, n = 1-3) with ozone. The precursor ions [M(MeIm)(OAc)](+) and [M(MeIm)(2)(OAc)](+) were generated via collision-induced dissociation of the corresponding [M(MeIm)(3)(OAc)](+) ion. The dependence of ozone reactivity on metal and coordination number is discussed. PMID- 20301109 TI - Determination of elemental compositions by gas chromatography/time-of-flight mass spectrometry using chemical and electron ionization. AB - Many metabolomic applications use gas chromatography/mass spectrometry (GC/MS) under standard 70 eV electron ionization (EI) parameters. However, the abundance of molecular ions is often extremely low, impeding the calculation of elemental compositions for the identification of unknown compounds. On changing the beam steering voltage of the ion source, the relative abundances of molecular ions at 70 eV EI were increased up to ten-fold for alkanes, fatty acid methyl esters and trimethylsilylated metabolites, concomitant with 2-fold absolute increases in ion intensities. We have compared the abundance, mass accuracy and isotope ratio accuracy of molecular species in EI with those in chemical ionization (CI) with methane as reagent gas under high-mass tuning. Thirty-three peaks of a diverse set of trimethylsilylated metabolites were analyzed in triplicate, resulting in 342 ion species ([M+H](+), [M-CH(3)](+) for CI and [M](+.), [M-CH(3)](+.) for EI). On average, CI yielded 8-fold more intense molecular species than EI. Using internal recalibration, average mass errors of 1.8 +/- 1.6 mm/z units and isotope ratio errors of 2.3 +/- 2.0% (A+1/A ratio) and 1.7 +/- 1.8% (A+2/A ratio) were obtained. When constraining lists of calculated elemental compositions by chemical and heuristic rules using the Seven Golden Rules algorithm and PubChem queries, the correct formula was retrieved as top hit in 60% of the cases and within the top-3 hits in 80% of the cases. PMID- 20301110 TI - The P-value illusion: how to improve (psychiatric) genetic studies. AB - There is an emerging appreciation that genome-wide association studies (GWAS) have failed to live up to expectations and deliver major advances to date. A "surge" strategy, of pooling resources and increasing number of subjects tested, is underway. We argue that, while useful, it will not be enough by itself. Complementary approaches are needed to mine these large datasets. We describe a series of problems, opportunities, and offer a potential comprehensive solution. PMID- 20301111 TI - Wide-angle light-scattering differentiation of organelle-size particle distributions in whole cells. AB - A finite-difference time-domain (FDTD) method is used to study the multiple scattering from many organelle-size particles distributed in a biological cell. Conventional flow cytometry, where the small-angle forward scatter (FSC) intensity and side scatter (SSC) intensity are used for cell characterizations, may have difficulties to differentiate the organelle distributions in biological cells. Based on the FDTD simulations, a light-scattering methodology is proposed here to overcome such a problem. This method differentiates the dense and sparse distributions of organelle-size particles in a cell, by counting the peak numbers in both large-angle FSC and wide-angle SSC, with the multiple scattering effects being considered. Implemented with a wide-angle microfluidic cytometer, the approach demonstrated in this theoretical study may find potential applications in clinics for label-free cell physiological study. PMID- 20301114 TI - Impact of chemotherapy on quality of life in patients with metastatic esophagogastric cancer. AB - BACKGROUND: Health-related quality of life (HRQoL) is a key issue in patients with metastatic esophagogastric cancer, a disease associated with survival times rarely exceeding 10 months. The objective of the current review was to evaluate the effects of chemotherapy on the HRQoL of patients with metastatic or locally advanced, inoperable esophagogastric cancer. METHODS: A systematic MEDLINE search was performed to address a predefined question list: Does chemotherapy improve or maintain HRQoL? Do available data favor a particular chemotherapy? What relation exists between HRQoL and the efficacy and tolerability of therapy? RESULTS: The majority of studies, including large randomized studies, indicated no significant improvements in mean HRQoL scores versus baseline after chemotherapy. However, scores were maintained and symptomatic relief or improved performance status was observed in many patients. HRQoL was maintained in approximately 50% of patients for up to 6 months but deteriorated in the remaining patients. In randomized phase 3 trials, only cisplatin/fluorouracil plus either docetaxel or epirubicin were found to provide superior HRQoL versus comparators. Between-regimen differences in HRQoL scores appeared to correspond to differences in the efficacy rather than the toxicity of treatment regimens. CONCLUSIONS: Chemotherapy maintained HRQoL in a substantial proportion of patients with advanced esophagogastric cancer. This effect appeared to correspond to the efficacy of the treatment. PMID- 20301112 TI - Increased fructose consumption is associated with fibrosis severity in patients with nonalcoholic fatty liver disease. AB - The rising incidence of obesity and diabetes coincides with a marked increase in fructose consumption. Fructose consumption is higher in individuals with nonalcoholic fatty liver disease (NAFLD) than in age-matched and body mass index (BMI)-matched controls. Because fructose elicits metabolic perturbations that may be hepatotoxic, we investigated the relationship between fructose consumption and disease severity in NAFLD. We studied 427 adults enrolled in the NASH Clinical Research Network for whom Block food questionnaire data were collected within 3 months of a liver biopsy. Fructose consumption was estimated based on reporting (frequency x amount) of Kool-aid, fruit juices, and nondietary soda intake, expressed as servings per week, and classified into none, minimum to moderate (<7 servings/week), and daily (> or =7 servings/week). The association of fructose intake with metabolic and histological features of NAFLD was analyzed using multiple linear and ordinal logistic regression analyses with and without controlling for other confounding factors. Increased fructose consumption was univariately associated with decreased age (P < 0.0001), male sex (P < 0.0001), hypertriglyceridemia (P < 0.04), low high-density lipoprotein (HDL) cholesterol (<0.0001), decreased serum glucose (P < 0.001), increased calorie intake (P < 0.0001), and hyperuricemia (P < 0.0001). After controlling for age, sex, BMI, and total calorie intake, daily fructose consumption was associated with lower steatosis grade and higher fibrosis stage (P < 0.05 for each). In older adults (age > or = 48 years), daily fructose consumption was associated with increased hepatic inflammation (P < 0.05) and hepatocyte ballooning (P = 0.05). CONCLUSION: In patients with NAFLD, daily fructose ingestion is associated with reduced hepatic steatosis but increased fibrosis. These results identify a readily modifiable environmental risk factor that may ameliorate disease progression in patients with NAFLD. PMID- 20301115 TI - Does MC1R genotype convey information about melanoma risk beyond risk phenotypes? AB - BACKGROUND: A study was carried out to describe associations of MC1R variants and melanoma in a US population and to investigate whether genetic risk is modified by pigmentation characteristics and sun exposure measures. METHODS: Melanoma patients (n = 960) and controls (n = 396) self-reported phenotypic characteristics and sun exposure via structured questionnaire and underwent a skin examination. Logistic regression was used to estimate associations of high- and low-risk MC1R variants and melanoma, overall and within phenotypic and sun exposure strata. A meta-analysis of results from published studies was undertaken. RESULTS: Carriage of 2 low-risk or any high-risk MC1R variants was associated with increased risk of melanoma (odds ratio [OR], 1.7; 95% confidence interval [CI], 1.0-2.8; and OR, 2.2; 95% CI, 1.5-3.0, respectively). However, risk was stronger in or limited to individuals with protective phenotypes and limited sun exposure, such as those who tanned well after repeated sun exposure (OR, 2.4; 95% CI, 1.6-3.6), had dark hair (OR, 2.4; 95% CI, 1.5-3.6), or had dark eyes (OR, 3.2; 95% CI, 1.8-5.9). We noted this same pattern of increased melanoma risk among persons who did not freckle, tanned after exposure to first strong summer sun, reported little or average recreational or occupational sun exposure, or reported no sun burning events. Meta-analysis of published literature supported these findings. CONCLUSIONS: These data indicate that MC1R genotypes provide information about melanoma risk in those individuals who would not be identified as high risk based on their phenotypes or exposures alone. PMID- 20301117 TI - Human mesenchymal stem cells and their use in cell-based therapies. AB - The human population is increasingly facing various diseases, including types of cancer, that cannot be cured with conventional drugs. Advanced drug targeting of tumor cells is also often impossible when treating highly invasive and infiltrative tumors such as glioblastoma or pulmonary cancer, because of tumor cells' high migration and invasiveness. Pluripotent human mesenchymal stem cells (hMSCs) have been extensively studied, and strategies are being proposed for treating "incurable" cancers and injury/disease-affected organs. Because of their own intrinsic properties, involving homing and immunomodulatory potency, hMSCs could be used as an excellent cell/drug delivery vehicle in those cell-based therapies. Their unprecedented use has been shadowed, however, by their spontaneous transformation, which links them to cancer-initiating cells during tumor development. How malignant initiation proceeds in vivo, and what are the exact characteristics of the cancer-initiating cells, still remain to be investigated. In the present review, the authors summed up the most recent knowledge about hMSC characteristics, their malignant transformation, and outlined the possibilities of their safe use in novel cell-based therapies. PMID- 20301118 TI - Effect of GroEL on thermal aggregation of glycogen phosphorylase b from rabbit skeletal muscle. AB - The suppression of the thermal aggregation of glycogen phosphorylase b (Phb) from rabbit skeletal muscle by the chaperonin GroEL is studied using dynamic light scattering. It is shown that the decrease in the rate of Phb aggregation under the action of GroEL is due to the transition of the aggregation process from the kinetic regime, wherein the rate of aggregation is limited by diffusion of the interacting particles, to a regime where the sticking probability for the colliding particles becomes lower than one (reaction-limited cluster-cluster aggregation). The analytical-ultracentrifugation data show that elevated temperatures induce dissociation of the dimeric Phb. The formation of a complex between the denatured monomeric form of Phb and the dissociated forms of GroEL is detected during heating at 46 degrees C. PMID- 20301119 TI - Improving the heat resistance of ribonuclease A by the addition of poly(N,N diethylaminoethyl methacrylate)-graft-poly(ethylene glycol) (PEAMA-g-PEG). AB - Poly(N,N-diethylaminoethyl methacrylate)-graft-poly(ethylene glycol) (PEAMA-g PEG) has previously been used as a novel additive to improve the heat resistance of lysozyme, which has a positive net charge and a negatively charged active site. In the present study, we show that PEAMA-g-PEG prevents heat inactivation of ribonuclease A (RNase A), which has a positive net charge and a positively charged active site. After treatment at 98 degrees C for 10 min, the enzymatic activity of RNase A complexed with PEAMA-g-PEG was maintained at up to 75% of the level of the native RNase A. The extents of inactivation of RNase A and the complex of RNase A with PEAMA-g-PEG were strongly dependent upon the heating temperature and incubation time. Circular dichroism (CD) spectral analysis revealed that heat-induced irreversible inactivation was largely suppressed when RNase A was complexed with PEAMA-g-PEG. These findings suggest that the heat resistance of RNase A is improved by the external addition of PEAMA-g-PEG. PMID- 20301120 TI - Response of human corneal fibroblasts on silk film surface patterns. AB - Transparent, biodegradable, mechanically robust, and surface-patterned silk films were evaluated for the effect of surface morphology on human corneal fibroblast (hCF) cell proliferation, orientation, and ECM deposition and alignment. A series of dimensionally different surface groove patterns were prepared from optically graded glass substrates followed by casting poly(dimethylsiloxane) (PDMS) replica molds. The features on the patterned silk films showed an array of asymmetric triangles and displayed 37-342 nm depths and 445-3 582 nm widths. hCF DNA content on all patterned films were not significantly different from that on flat silk films after 4 d in culture. However, the depth and width of the grooves influenced cell alignment, while the depth differences affected cell orientation; overall, deeper and narrower grooves induced more hCF orientation. Over 14 d in culture, cell layers and actin filament organization demonstrated that confluent hCFs and their cytoskeletal filaments were oriented along the direction of the silk film patterned groove axis. Collagen type V and proteoglycans (decorin and biglycan), important markers of corneal stromal tissue, were highly expressed with alignment. Understanding corneal stromal fibroblast responses to surface features on a protein-based biomaterial applicable in vivo for corneal repair potential suggests options to improve corneal tissue mimics. Further, the approaches provide fundamental biomaterial designs useful for bioengineering oriented tissue layers, an endemic feature in most biological tissue structures that lead to critical tissue functions. PMID- 20301121 TI - Manipulating CD4+ T cells by optical tweezers for the initiation of cell-cell transfer of HIV-1. AB - Cell-cell interactions through direct contact are very important for cellular communication and coordination - especially for immune cells. The human immunodeficiency virus type I (HIV-1) induces immune cell interactions between CD4(+) cells to shuttle between T cells via a virological synapse. A goal to understand the process of cell-cell transmission through virological synapses is to determine the cellular states that allow a chance encounter between cells to become a stable cell-cell adhesion. We demonstrate the use of optical tweezers to manipulate uninfected primary CD4(+) T cells near HIV Gag-iGFP transfected Jurkat T cells to probe the determinants that induce stable adhesion. When combined with fast 4D confocal fluorescence microscopy, optical tweezers can be utilized not only to facilitate cell-cell contact, but also to simultaneously track the formation of a virological synapse, and ultimately to probe the events that precede virus transfer. PMID- 20301122 TI - Optical micromanipulations in the non-diffractive regime. AB - The ever-evolving topic of optical micromanipulation has established itself as a discipline over the last three decades, and is of much interest to a wide research community due to constantly emerging new applications across the various key disciplines. Performing optical manipulation using evanescent waves is termed near-field optical manipulation, which is essentially the manipulation of particles in the non-diffractive regime. The concept of the breaking of diffraction limit is the spur driving near-field optics studies, as opposed to all far field optical applications where light cannot be focused to a spot smaller than the diffraction limited value, which is about half the wavelength of light in the medium. The authors present a review of the various near-field optical manipulation techniques and then report on the observation of erythrocyte pearl chains by a near-field optical tweezer. PMID- 20301123 TI - Optofluidic chip for single cell trapping and stretching fabricated by a femtosecond laser. AB - The authors present the design and optimization of an optofluidic monolithic chip, able to provide optical trapping and controlled stretching of single cells. The chip is fabricated in a fused silica glass substrate by femtosecond laser micromachining which can produce both optical waveguides and microfluidic channels with great accuracy. A new fabrication procedure adopted in this work allows the demonstration of microchannels with a square cross-section, thus guaranteeing an improved quality of the trapped cell images. Femtosecond laser micromachining emerges as a promising technique for the development of multifunctional integrated biophotonic devices that can be easily coupled to a microscope platform, thus enabling a complete characterization of the cells under test. PMID- 20301124 TI - Real time characterization of hydrodynamics in optically trapped networks of micro-particles. AB - The hydrodynamic interactions of micro-silica spheres trapped in a variety of networks using holographic optical tweezers are measured and characterized in terms of their predicted eigenmodes. The characteristic eigenmodes of the networks are distinguishable within 20-40 seconds of acquisition time. Three different multi-particle networks are considered; an eight-particle linear chain, a nine-particle square grid and, finally, an eight-particle ring. The eigenmodes and their decay rates are shown to behave as predicted by the Oseen tensor and the Langevin equation, respectively. Finally, we demonstrate the potential of using our micro-ring as a non-invasive sensor to the local environmental viscosity, by showing the distortion of the eigenmode spectrum due to the proximity of a planar boundary. PMID- 20301125 TI - Particle trapping using dielectrophoretically patterned carbon nanotubes. AB - This study presents the dielectrophoretic (DEP) assembly of multi-walled carbon nanotubes (MWCNTs) between curved microelectrodes for the purpose of trapping polystyrene microparticles within a microfluidic system. Under normal conditions, polystyrene particles exhibit negative DEP behaviour and are repelled from microelectrodes. Interestingly, the addition of MWCNTs to the system alters this situation in two ways: first, they coat the surface of particles and change their dielectric properties to exhibit positive DEP behaviour; second, the assembled MWCNTs are highly conductive and after the deposition serve as extensions to the microelectrodes. They establish an array of nanoelectrodes that initiates from the edge of microelectrodes and grow along the electric field lines. These nanoelectrodes can effectively trap the MWCNT-coated particles, since they cover a large portion of the microchannel bottom surface and also create a much stronger electric field than the primary microelectrodes as confirmed by our numerical simulations. We will show that the presence of MWCNT significantly changes performance of the system, which is investigated by trapping sample polystyrene particles with plain, COOH and goat anti-mouse IgG surfaces. PMID- 20301126 TI - Continuous dielectrophoretic separation of particles in a spiral microchannel. AB - Particle separation is a fundamental operation in the areas of biology and physical chemistry. A variety of force fields have been used to separate particles in microfluidic devices, among which electric field may be the most popular one due to its general applicability and adaptability. So far, however, electrophoresis-based separations have been limited primarily to batchwise processes. Dielectrophoresis (DEP)-based separations require in-channel micro electrodes or micro-insulators to produce electric field gradients. This article introduces a novel particle separation technique in DC electrokinetic flow through a planar double-spiral microchannel. The continuous separation arises from the cross-stream dielectrophoretic motion of particles induced by the non uniform electric field inherent to curved channels. Specifically, particles are focused by DEP to one sidewall of the first spiral, and then dielectrophoretically deflected toward the other sidewall of the second spiral at a particle-dependent rate, leading to focused particle streams along different flow paths. This DEP-based particle separation technique is demonstrated in an asymmetric double-spiral microchannel by continuously separating a mixture of 5/10 microm particles and 3/5 microm particles. PMID- 20301127 TI - Pumpless dispensing of a droplet by breaking up a liquid bridge formed by electric induction. AB - Dispensing uniform pico-to-nanoliter droplets has become one of essential components in various application fields from high-throughput bio-analysis to printing. In this study, a new method is suggested and demonstrated for dispensing a droplet on the top plate with an inverted geometry by using electric field. The process of dispensing droplets consists of two stages: (i) formation of liquid bridge by moving up the charged fluid mass using the electrostatic force between the charges on the fluid mass and the induced charges on the substrate and (ii) its break-up by the motion of the top plate. Different from conventional electrohydrodynamic methods, electric induction enables the droplets to be dispensed on various surfaces including non-conducting substrate. The use of capillarity with an inverted geometry removes the need of external pumps or elaborates control for constant flow feed. The droplet diameter has been characterized as a function of the nozzle-to-plate distance and the plate moving velocity. The robustness of the present method is shown in terms of nozzle length and applied voltage. Finally, its practical applicability is confirmed by rendering a 19 by 24 array of highly uniform droplets with only 1.8% size variation without use of any active feedback control. PMID- 20301129 TI - Ultrahigh-energy-density microbatteries enabled by new electrode architecture and micropackaging design. PMID- 20301130 TI - Controlling electronic States and transport properties at the level of single molecules. AB - Since molecular electronics has been rapidly growing as a promising alternative to conventional electronics towards the ultimate miniaturization of electronic devices through the bottom-up strategy, it has become a long-term desire to understand and control the transport properties at the level of single molecules. In this Research News article it is shown that one may modify the electronic states of single molecules and thus control their transport properties through designing and fabrication of functional molecules or manipulating molecules with scanning tunneling microscopy. The rectifying effect of single molecules can be realized by designing a donor-barrier-acceptor architecture of Pyridine-sigma C(60) molecules to achieve the Aviram-Ratner rectifier and by modifying electronic states through azafullerene C(59)N molecules. The effect of the negative differential resistances can be realized by appropriately matching the molecular orbital symmetries between a cobalt phthalocyanine (CoPc) molecule and a Ni electrode. The electronic states and transport properties of single molecules, such as CoPc and melamine molecules, can be altered through manipulation or modifying molecular structures, leading to functionalized molecular devices. PMID- 20301132 TI - Seed-mediated synthesis of truncated gold decahedrons with a AuCl/oleylamine complex as precursor. PMID- 20301133 TI - Gold-based hybrid nanocrystals through heterogeneous nucleation and growth. PMID- 20301134 TI - Iso-structural phase transitions in BiFeO3. PMID- 20301131 TI - Glyconanomaterials: synthesis, characterization, and ligand presentation. AB - Glyconanomaterials, nanomaterials carrying surface-tethered carbohydrate ligands, have emerged and demonstrated increasing potential in biomedical imaging, therapeutics, and diagnostics. These materials combine the unique properties of nanometer-scale objects with the ability to present multiple copies of carbohydrate ligands, greatly enhancing the weak affinity of individual ligands to their binding partners. Critical to the performance of glyconanomaterials is the proper display of carbohydrate ligands, taking into consideration of the coupling chemistry, the type and length of the spacer linkage, and the ligand density. This article provides an overview of the coupling chemistry for attaching carbohydrate ligands to nanomaterials, and discusses the need for thorough characterization of glyconanomaterials, especially quantitative analyses of the ligand density and binding affinities. Using glyconanoparticles synthesized by a versatile photocoupling chemistry, methods for determining the ligand density by colorimetry and the binding affinity with lectins by a fluorescence competition assay are determined. The results show that the multivalent presentation of carbohydrate ligands significantly enhances the binding affinity by several orders of magnitude in comparison to the free ligands in solution. The effect is sizeable even at low surface ligand density. The type and length of the spacer linkage also affect the binding affinity, with the longer linkage promoting the association of bound ligands with the corresponding lectins. PMID- 20301135 TI - Characterization of complex assemblages of organic acids in geological samples by negative electrospray ionization mass spectrometry using a double-focusing magnetic sector field mass spectrometer. AB - Four different geological sample types (a crude oil, a crude oil asphaltene, a reservoir core extract and a reservoir core asphaltene) have been characterized by negative ionization electrospray mass spectrometry at low and high mass resolution using a double-focusing magnetic sector field mass spectrometer. The mass range, shape of the spectra and the signal distribution of the acidic constituents as well as the average molecular weights, the total ion abundance and signal intensity in the spectra were compared for the different sample types. Nominal mass classes have been evaluated and Kendrick mass plots were generated in order to identify homologous series. For the crude oil sample, accurate mass assignments were made by high-resolution double-focusing magnetic sector field mass spectrometry (DFMSFMS) and were compared with those obtained by negative ion electrospray ionization (ESI) Fourier transform ion cyclotron resonance mass spectrometry (FTICRMS). With both instrument types, compounds with the molecular composition C(n)H(2n+z)O(2), among which carboxylic acids predominated, were the main acidic compound class detectable in negative ESI mass spectra. Good agreement was achieved for the double bond class distribution and the carbon number distribution of the O(2) class. In addition, minor compound classes could be identified using FTICRMS. PMID- 20301136 TI - Exploring rearrangements along the fragmentation of glutaric acid negative ion: a combined experimental and theoretical study. AB - Glutaric acid, a common short-chain aliphatic dicarboxylic acid, was investigated in the negative ion mode by subjecting its [M-H](-) ion to collision-induced dissociation (CID) experiments in an infinity ion cyclotron resonance (ICR) cell coupled to a hexapole-quadrupole-hexapole ion guide. A 12 Tesla magnet was used for high-resolution measurements. Two distinctive main pathways were observed in the MS/MS spectrum. The fragmentation pathways were also thoroughly investigated in a density functional theory (DFT) study involving a B3LYP/6 311+G(2d,p)//B3LYP/6-311+G(d,p) level of theory. Elimination of CO(2) from the [M H](-) ion of the dicarboxylic acid takes place in a concerted mechanism, by which a 1,5 proton shift occurs from the intact carboxyl group to the methylene moiety located in the alpha position relative to the deprotonated carboxyl group. This concerted mechanism stabilizes the terminal negative charge and deprotonates the second carboxylic acid group. Water elimination from the [M-H](-) ion does not take place by means of a simple proton removal from the alpha methylene group - and OH(-) release from the carboxylate group to abstract an additional alpha proton thus leading to the formation of a deprotonated ketene anion. In the case of this dicarboxylic acid, a new mechanism was found for water elimination, which differs from that known for aliphatic monocarboxylic acids. An intramolecular interaction between the deprotonated and the intact carboxyl groups plays a key role in making a new energetically favourable mechanism. The DFT study also reveals that a combined loss of CO2 and H2O in the form of H2CO3 is possible. PMID- 20301137 TI - Social group norms, school norms, and children's aggressive intentions. AB - This study examined whether the effect of social group norms on 7- and 10-year old children's aggression can be moderated or extinguished by contrary school norms. Children (n=384) participated in a simulation in which they were assigned membership in a social group for a drawing competition against an outgroup. Participants learnt that their group had a norm of inclusion, exclusion, or exclusion-plus-relational aggression, toward non-group members, and that the school either had a norm of inclusion, or no such norm. Findings indicated that group norms influenced the participants' direct and indirect aggressive intentions, but that the school norm moderated the group norm effect, with the school's norm effect tending to be greater for indirect vs. direct aggression, males vs. females, and younger vs. older participants. Discussion focused on how school norms can be developed, endorsed, and presented so that they have their most lasting effect on children. PMID- 20301138 TI - Local attitudes and perceptions toward crop-raiding by orangutans (Pongo abelii) and other nonhuman primates in northern Sumatra, Indonesia. AB - Human-wildlife conflicts, such as crop-raiding, increase as people expand their agricultural activities into wildlife habitats. Crop-raiding can reduce tolerance toward species that are already threatened, whereas potential dangers posed by conflicts with large-bodied species may also negatively influence local attitudes. Across Asia, wild pigs and primates, such as macaques, tend to be the most commonly reported crop raiders. To date, reports of crop-raiding incidents involving great apes have been less common, but incidents involving orangutans are increasingly emerging in Indonesia. To investigate the interplay of factors that might explain attitudes toward crop-raiding by orangutans (Pongo abelii), focal group discussions and semi-structured interviews were conducted among 822 farmers from 2 contrasting study areas in North Sumatra. The first study area of Batang Serangan is an agroforest system containing isolated orangutans that crop raid. In contrast, the second area of Sidikalang comprises farmlands bordering extensive primary forest where orangutans are present but not reported to crop raid. Farmers living in Batang Serangan thought that orangutans were dangerous, irrespective of earlier experience of crop-raiding. Farmers placed orangutans as the third most frequent and fourth most destructive crop pest, after Thomas' leaf monkey (Presbytis thomasi), wild boar (Sus scrofa), and long-tailed macaque (Macaca fascicularis). Although most (57%) farmers across both study areas were not scared of wildlife species, more than a quarter (28%) of the farmers' feared orangutans. Farmers in Batang Serangan were generally more tolerant toward crop raiding orangutans, if they did not perceive them to present a physical threat. Most (67%) Batang Serangan farmers said that the local Forestry Department staff should handle crop-raiding orangutans, and most (81%) said that these officials did not care about such problems. Our results suggest that efforts to mitigate human-orangutan conflict may not, per se, change negative perceptions of those who live with the species, because these perceptions are often driven by fear. PMID- 20301139 TI - Time course of vocal modulation during isolation in common marmosets (Callithrix jacchus). AB - Common marmosets vocalize phee calls as isolation calls, which seem to facilitate their reunion with family groups. To identify multiple acoustic properties with different time courses, we examined acoustic modulations of phees during different social contexts of isolation. Subject marmosets were totally isolated in one condition, were visually isolated and could exchange vocalizations in another condition, and were visually isolated and subsequently totally isolated in a third condition. We recorded 6,035 phees of 10 male-female marmoset pairs and conducted acoustic analysis. The marmosets frequently vocalized phees that were temporally elongated and louder during isolation, with varying time courses of these changes in acoustic parameters. The vocal rates and sound levels of the phees increased as soon as the marmosets saw their pair mates being taken away, and then gradually calmed down. The phee duration was longer in conditions during which there were no vocal responses from their pair mates. Louder vocalizations are conspicuous and seem to be effective for long-distance transmission, whereas shorter call duration during vocal exchanges might avoid possible vocal overlap between mates. PMID- 20301140 TI - The use of fluid boluses to safely perform extracorporeal photopheresis (ECP) in low-weight children: a novel procedure. AB - Apheresis procedures in small children are technically challenging and require special planning with attention to extracorporeal volume. Discontinuous procedures such as extracorporeal photopheresis (ECP) require additional consideration. Alternative methods to perform ECP have been utilized in small children that require manipulation of mononuclear cells outside the standard closed-loop system. We present a safe and feasible alternative to the procedure for children who weigh less than 40 Kg, while maintaining a closed loop, sterile system utilizing the UVAR XTS device. A retrospective chart review was performed analyzing the use of fluid boluses (normal saline in those between 20 and 40 Kg, 5% albumin in those under 20 Kg) before ECP. Eleven patients underwent 334 ECP procedures for acute and chronic graft-versus-host disease (n = 9), and for prevention of graft-versus-host disease (n = 2). Volumes of fluid boluses were calculated based on the expected extracorporeal volume during the first draw cycle. Treatments consisted of at least three draw cycles using the 125 mL bowl. The median weight was 28.5 Kg (range 19 to 39); nine of 11 required red cell transfusions to maintain adequate hematocrit. Complications attributed to ECP included tachycardia, dizziness, nausea, and hypotension; these occurred either in combination or isolation in 31% of the procedures and resolved following additional fluid boluses. Only three (0.8%) required early photoactivation due to these complications. The median time to completion of treatment was 2 h and 58 min (range 1:30 to 5:03). ECP is well tolerated in low-weight pediatric patients if hematocrit and hydration are carefully maintained. PMID- 20301142 TI - Cyclometalated Ir(III) complexes with substituted 1,10-phenanthrolines: a new class of efficient cationic organometallic second-order NLO chromophores. AB - Cyclometalated cationic Ir(III) complexes with substituted 1,10-phenanthrolines (1,10-phen), such as [Ir(ppy)(2)(5-R-1,10-phen)]Y (ppy=cyclometalated 2 phenylpyridine; R=NO(2), H, Me, NMe(2); Y(-)=PF(6) (-), C(12)H(25)SO(3) (-), I( )) and [Ir(ppy)(2)(4-R,7-R-1,10-phen)]Y (R=Me, Ph) are characterized by a significant second-order optical non linearity (measured by the electrical field induced second harmonic generation (EFISH) technique). This nonlinearity is controlled by MLCT processes from the cyclometalated Ir(III), acting as a donor push system, to pi* orbitals of the phenanthroline, acting as an acceptor pull system. Substitution of cyclometalated 2-phenylpyridine by the more pi delocalized 2-phenylquinoline (pq) or benzo[h]quinoline (bzq) or by the sulfur containing 4,5-diphenyl-2-methyl-thiazole (dpmf) does not significantly affect the mubeta absolute value, which instead is affected by the nature of the R substituents on the phenanthroline, the higher value being associated with the electron-withdrawing NO(2) group. By using a combined experimental (the EFISH technique and (1)H and (19)F PGSE NMR spectroscopy) and theoretical (DFT, time dependent-DFT (TDDFT), sum over states (SOS) approach) investigation, evidence is obtained that ion pairing, which is controlled by the nature of the counterion and by the concentration, may significantly affect the mubeta values of these cationic NLO chromophores. In CH(2)Cl(2), concentration-dependent high absolute values of mubeta are obtained for [Ir(ppy)(2)(5-NO(2)-1,10-phen)]Y if Y is a weakly interacting anion, such as PF(6) (-), whereas with a counterion, such as C(12)H(25)SO(3) (-) or I(-), which form tight ion-pairs, the absolute value of mubeta is lower and quite independent of the concentration. This mubeta trend is partially due to the perturbation of the counterion on the LUMO pi* levels of the phenanthroline. The correlation between the mubeta value and dilution shows that the effect of concentration is a factor that must be taken into careful consideration. PMID- 20301143 TI - The effect of the equatorial environment on oxo-group silylation of the uranyl dication: a computational study. AB - A theoretical investigation of the reductive oxo-group silylation reaction of the uranyl dication held in a Pacman macrocylic environment has been carried out. The effect of the modeling of the Pacman ligand on the reaction profiles is found to be important, with the dipotassiation of a single oxo group identified as a key component in promoting the reaction between the Si-X and uranium-oxo bonds. This reductive silylation reaction is also proposed to occur in an aqueous environment but was found not to operate on bare ions; in this latter case, substitution of a ligand in the equatorial plane was the most likely reaction. These results demonstrate the importance of the presence but not the identity of the equatorial ligands upon the silylation of the uranyl U-O bond. PMID- 20301144 TI - Increasing the sensitivity and single-base mismatch selectivity of the molecular beacon using graphene oxide as the "nanoquencher". AB - Here, we report a novel, highly sensitive, selective and economical molecular beacon using graphene oxide as the "nanoquencher". This novel molecular beacon system contains a hairpin-structured fluorophore-labeled oligonucleotide and a graphene oxide sheet. The strong interaction between hairpin-structured oligonucleotide and graphene oxide keep them in close proximity, facilitating the fluorescence quenching of the fluorophore by graphene oxide. In the presence of a complementary target DNA, the binding between hairpin-structured oligonucleotide and target DNA will disturb the interaction between hairpin-structured oligonucleotide and graphene oxide, and release the oligonucleotide from graphene oxide, resulting in restoration of fluorophore fluorescence. In the present study, we show that this novel graphene oxide quenched molecular beacon can be used to detect target DNA with higher sensitivity and single-base mismatch selectivity compared to the conventional molecular beacon. PMID- 20301145 TI - From a network of computed reaction enthalpies to atom-based thermochemistry (NEAT). AB - A simple and fast, weighted, linear least-squares refinement protocol and code is presented for inverting the information contained in a network of quantum chemically computed 0 K reaction enthalpies. This inversion yields internally consistent 0 K enthalpies of formation for the species of the network. The refinement takes advantage of the fact that the accuracy of computed enthalpies depends strongly on the quantum-chemical protocol employed for their determination. Different protocols suffer from different sources of error; thus, the reaction enthalpies computed by them have "random" residual errors. Since it is much more natural for quantum-chemical energy and enthalpy results, including reaction enthalpies, to be based on the electronic ground states of the atoms and not on the historically preferred elemental states, and since these two possible protocols can be converted into each other straightforwardly, it is proposed that first-principles thermochemistry should employ the ground electronic states of atoms. In this scheme, called atom-based thermochemistry (AT), the enthalpy of formation of a gaseous compound corresponds simply to the total atomization energy of the species; it is always positive, and it reflects the bonding strength within the molecule. The inversion protocol developed and based on AT is termed NEAT, which represents the fact that the protocol proceeds from a network of computed reaction enthalpies toward atom-based thermochemistry, most directly to atom-based enthalpies of formation. After assembling a database that consisted of 361 ab initio reactions and reaction enthalpies involving 188 species, collected from 31 literature sources, the following dependable 0 K atom-based enthalpies of formation, Delta(f)${H{{{?rm AT}?hfill ?atop 0?hfill}}}$, all in kJ mol(-1), have been obtained by means of NEAT: H(2)=432.07(0), CH=334.61(15), NH=327.69(25), OH=425.93(21), HF=566.13(31), CO=1072.08(28), O(2)=493.51(34), CH(2)=752.40(21), H(2)O=918.05(20), HO(2)=694.53(32), CO(2)=1597.77(40), CH(3)=1209.64(29), NH(3)=1157.44(33), C(2)H(2)=1625.78(40), and CH(4)=1641.68(40), in which the uncertainty values given in parentheses represent 95 % confidence intervals. The average deviation of these values from the well established active thermochemical tables (ATcT) values is a mere 0.25 kJ mol(-1), with a maximum deviation of 0.7 kJ mol(-1). This shows that the use of a large number of ab initio reaction enthalpies within a NEAT-type protocol has considerable advantages over the sequential utilization of the ab initio information. PMID- 20301146 TI - Rhenium(I)-catalyzed cyclization of silyl enol ethers containing a propargyl carboxylate moiety: versatile access to highly substituted phenols. PMID- 20301147 TI - Asymmetric retro- and transfer-aldol reactions catalyzed by a simple chiral primary amine. AB - One stone four birds: A single chiral primary amine was found to catalyze unprecedented asymmetric retro-aldol and transfer-aldol reactions, leading to four different chiral aldol adducts from one common chiral source with up to 99:1 d.r. and 99 % ee (see scheme). PMID- 20301148 TI - Competitive hydrogen-atom abstraction versus oxygen-atom and electron transfers in gas-phase reactions of [X4O10].+ (X = P, V) with C2 H4. AB - Why so different? The comparison of the reaction of "bare" [P4O10](.+) and [V4O10](.+) with ethene by mass-spectrometric and computational studies permits insight into mechanistic aspects of the competition between C-H bond activation and oxygen-atom and electron transfers. Whereas [P4O10](.+) reacts by homolytic C H bond cleavage and electron transfer, the isostructural [V4O10](.+) shows only oxygen-atom transfer (see picture). PMID- 20301149 TI - Sub-mol % catalyst loading and ligand-acceleration in the copper-catalyzed coupling of aryl iodides and terminal alkyenes. PMID- 20301150 TI - Small-molecule affinity ligands for protein purification: combined computational enrichment and automated in-line screening of an optically encoded library. PMID- 20301151 TI - Synthesis and properties of a fifteen-coordinate complex: the thorium aminodiboranate [Th(H3BNMe2BH3)4]. PMID- 20301152 TI - Enantioselective adsorption in achiral zeolites. PMID- 20301153 TI - Modular inorganic nanocomposites by conversion of nanocrystal superlattices. AB - Inorganic nanocomposites have been prepared by assembling colloidal nanocrystals and then replacing the organic ligands with precursors to an inorganic matrix phase. Separate synthesis and processing of the nanocrystal and matrix phases allows complete compositional modularity and retention of the superlattice morphologies for sphere (see scheme; top) or rod (bottom) assemblies. PMID- 20301154 TI - The ouroborand: a cavitand with a coordination-driven switching device. PMID- 20301155 TI - Sensitive detection of native proteins using extractive electrospray ionization mass spectrometry. PMID- 20301157 TI - Tunable bromomagnesium thiolate Tishchenko reaction catalysts: intermolecular aldehyde-trifluoromethylketone coupling. PMID- 20301158 TI - Concise synthesis of (-)-nakadomarin A. AB - The beautiful orchestration of new methods and synthesis design was instrumental to the very efficient synthesis of the manzamine alkaloid (-)-nakadomarin A. In only six operations, the two relatively simple compounds shown were converted into the hexacyclic natural product. PMID- 20301159 TI - Direct, one-pot sequential reductive alkylation of lactams/amides with Grignard and organolithium reagents through lactam/amide activation. PMID- 20301160 TI - Substrate conformations set the rate of enzymatic acrylation by lipases. AB - Acrylates represent a class of alpha,beta-unsaturated compounds of high industrial importance. We investigated the influence of substrate conformations on the experimentally determined reaction rates of the enzyme-catalysed transacylation of methyl acrylate and derivatives by ab initio DFT B3LYP calculations and molecular dynamics simulations. The results supported a least motion mechanism upon the sp(2) to sp(3) substrate transition to reach the transition state in the enzyme active site. This was in accordance with our hypothesis that acrylates form productive transition states from their low-energy s-sis/s-trans conformations. Apparent k(cat) values were measured for Candida antarctica lipase B (CALB), Humicola insolens cutinase and Rhizomucor miehei lipase and were compared to results from computer simulations. More potent enzymes for acryltransfer, such as the CALB mutant V190A and acrylates with higher turnover numbers, showed elevated populations of productive transition states. PMID- 20301161 TI - RNA-cleaving deoxyribozyme sensor for nucleic acid analysis: the limit of detection. AB - Along with biocompatibility, chemical stability, and simplicity of structural prediction and modification, deoxyribozyme-based molecular sensors have the potential of an improved detection limit due to their ability to catalytically amplify signal. This study contributes to the understanding of the factors responsible for the limit of detection (LOD) of RNA-cleaving deoxyribozyme sensors. A new sensor that detects specific DNA/RNA sequences was designed from deoxyribozyme OA-II [Chiuman, W.; Li, Y. (2006) J. Mol. Biol. 357, 748-754]. The sensor architecture allows for a unique combination of high selectivity, low LOD and the convenience of fluorescent signal monitoring in homogeneous solution. The LOD of the sensor was found to be approximately 1.6 x 10(-10) M after 3 h of incubation. An equation that allows estimation of the lowest theoretical LOD using characteristics of parent deoxyribozymes and their fluorogenic substrates was derived and experimentally verified. According to the equation, "catalytically perfect" enzymes can serve as scaffolds for the design of sensors with the LOD not lower than approximately 2 x 10(-15) M after 3 h of incubation. A new value termed the detection efficiency (DE) is suggested as a time independent characteristic of a sensor's sensitivity. The expressions for the theoretical LOD and DE can be used to evaluate nucleic acid and protein enzymes for their application as biosensing platforms. PMID- 20301162 TI - RNA grooves can accommodate disulfide-bridged bundles of alpha-helical peptides. PMID- 20301163 TI - Endoscopic resection of early gastric cancer treated by guideline and expanded National Cancer Centre criteria. AB - BACKGROUND: Criteria for endoscopic resection in patients with early gastric cancer (EGC) have been expanded recently by the National Cancer Centre (NCC). This study compared long-term outcomes in patients with EGC who underwent endoscopic treatment according to guideline criteria with those treated according to expanded criteria. METHODS: Baseline and outcome data from patients undergoing curative endoscopic resection for EGC between January 1999 and December 2005 were collected from electronic medical records. Survival time hazard ratios and 95 per cent confidence intervals were calculated using the Cox proportional hazards model. RESULTS: Of 1485 patients who had a curative resection, 635 (42.8 per cent) underwent resection according to traditional criteria and 625 (42.1 per cent) according to expanded criteria. There was no significant difference in overall survival between the groups. CONCLUSION: Patients who have treatment following the expanded criteria have similar long-term survival and outcomes to those treated according to guideline criteria. PMID- 20301164 TI - Mechanisms of RNA degradation by the eukaryotic exosome. PMID- 20301165 TI - Outcome of elderly patients with oesophageal squamous cell carcinoma after surgery. AB - BACKGROUND: Oesophagectomy may have morbidity and mortality rates that severely compromise long-term survival in elderly patients. The aim of this study was to compare clinical outcomes in elderly patients with oesophageal squamous cell carcinoma (SCC) with those of younger controls. METHODS: Elderly patients at least 70 years old with oesophageal SCC were matched 1 : 1 with controls aged less than 70 years according to sex, tumour stage, tumour location, histological grade, surgical approach, completeness of resection and surgical period. Co morbidities, surgical complications, surgical mortality and long-term survival were compared. RESULTS: One hundred and thirty-six patients were included in each group. Surgical mortality was greater in the elderly group (5.9 versus 0.7 per cent; P = 0.036). Overall and disease-specific 5-year survival rates were worse among patients aged at least 70 years (30.0 versus 41.8 per cent, and 31.5 versus 44.7 per cent respectively), as were 10-year rates (13.7 versus 26.4 per cent, and 20.2 versus 29.0 per cent). Disease-free survival rates after 5 years (24.0 versus 35.5 per cent) and 10 years (12.3 versus 24.3 per cent) were not statistically significant (P = 0.076). CONCLUSION: Poor functional status may account for higher morbidity and mortality rates in elderly patients with oesophageal SCC. Acceptable perioperative mortality rates and substantial long term survival can still be achieved. Elderly patients should not be denied oesophagectomy. PMID- 20301167 TI - MicroRNA profiling of Barrett's oesophagus and oesophageal adenocarcinoma. AB - BACKGROUND: The genetic changes that drive metaplastic progression from squamous oesophageal mucosa toward intestinal metaplasia and adenocarcinoma are unclear. The aberrant expression of microRNAs (miRNAs) is involved in the development of cancer. This study examined whether miRNAs play a role in the development of oesophageal adenocarcinoma. METHODS: RNA was extracted from mucosa of normal oesophageal squamous epithelium, normal gastric epithelium, Barrett's oesophagus with intestinal metaplasia and oesophageal adenocarcinoma obtained from 16 individuals. Expression profiles of 377 human miRNAs were determined by microarray analysis and selected miRNAs were analysed further using real-time reverse transcription-polymerase chain reaction (RT-PCR) in tissues from 32 individuals. RESULTS: Microarray analyses identified 44 miRNAs likely to have altered expression between various mucosal samples. Of these, miR-21, miR-143, miR-145, miR-194, miR-203, miR-205 and miR-215 were chosen for validation by real time RT-PCR. Tissue-specific expression profiles were observed, with miR-21, miR 143, miR-145, miR-194 and miR-215 significantly upregulated in columnar tissues compared with normal squamous epithelium. Expression of miR-143, miR-145 and miR 215 was lower in oesophageal adenocarcinoma than in Barrett's oesophagus. Levels of miR-203 and miR-205 were high in normal squamous epithelium and low in columnar epithelia. MiR-205 levels were lower in gastric epithelium than in both Barrett's oesophagus and adenocarcinoma. CONCLUSION: Expression of miRNA might define disease states in oesophageal epithelium. Dysregulation of specific miRNAs could contribute to metaplastic and neoplastic processes in the oesophageal mucosa. PMID- 20301168 TI - Images come to life. PMID- 20301166 TI - Photocaged t7 RNA polymerase for the light activation of transcription and gene function in pro- and eukaryotic cells. AB - A light-activatable bacteriophage T7 RNA polymerase (T7RNAP) has been generated through the site-specific introduction of a photocaged tyrosine residue at the crucial position Tyr639 within the active site of the enzyme. The photocaged tyrosine disrupts polymerase activity by blocking the incoming nucleotide from reaching the active site of the enzyme. However, a brief irradiation with nonphototoxic UV light of 365 nm removes the ortho-nitrobenzyl caging group from Tyr639 and restores the RNA polymerase activity of T7RNAP. The complete orthogonality of T7RNAP to all endogenous RNA polymerases in pro- and eukaryotic systems allowed for the photochemical activation of gene expression in bacterial and mammalian cells. Specifically, E. coli cells were engineered to produce photocaged T7RNAP in the presence of a GFP reporter gene under the control of a T7 promoter. UV irradiation of these cells led to the spatiotemporal activation of GFP expression. In an analogous fashion, caged T7RNAP was transfected into human embryonic kidney (HEK293T) cells. Irradiation with UV light led to the activation of T7RNAP, thereby inducing RNA polymerization and expression of a luciferase reporter gene in tissue culture. The ability to achieve spatiotemporal regulation of orthogonal RNA synthesis enables the precise dissection and manipulation of a wide range of cellular events, including gene function. PMID- 20301169 TI - Direct analysis of lipids in mouse brain using electrospray droplet impact/SIMS. AB - Electrospray droplet impact (EDI)/secondary ion mass spectrometry (SIMS) is a new desorption/ionization technique for mass spectrometry in which highly charged water clusters produced from the atmospheric-pressure electrospray are accelerated in vacuum by 10 kV and impact the sample deposited on the metal substrate. EDI/SIMS was shown to enhance intact molecular ion formation dramatically compared to conventional SIMS. EDI/SIMS has been successfully applied to the analysis of mouse brain without any sample preparation. Five types of lipids, i.e. phosphatidylcholine (PC), phosphatidylserine, phosphatidylinositol (PI), galactocerebroside (GC) and sulfatide (ST), were readily detected from mouse brain section. In addition, by EDI/SIMS, six different regions of the mouse brain (cerebral cortex, corpus callosum, striatum, medulla oblongata, cerebellar cortex and cerebellar medulla) were examined. While GCs and STs were found to be rich in white matter, PIs were rich in gray matter. PMID- 20301170 TI - Assembly of gold nanoparticles on a molecular ultrathin film: tuning the surface plasmon resonance. AB - A number of methodologies for immobilizing metal nanoparticles in 2-dimensional aggregate structures on various substrates, some with concomitant tuning of the surface plasmon resonance (SPR), have been reported. Many of them involve special functionalization of the nanoparticles, multiple fabrication steps or lengthy procedures. The present study demonstrates that monolayer Langmuir-Blodgett (LB) film of a hemicyanine-based amphiphile with cationic headgroup is an easily fabricated platform for harnessing citrate-stabilized gold nanoparticles. It is shown that a single immersion step can be used to immobilize the nanoparticles uniformly on large area films and that systematic variation of the immersion time from 10 min to 6 h leads to controlled assembly of the particles and tuning of the SPR band over approximately 100 nm. A model for the structural reorganization in the LB film that facilitates the assembly of nanoparticles is presented and the advantages of the current methodology over earlier protocols are pointed out. The versatility of LB films in terms of the molecular level control of fabrication it enables and the variety of film structures that can be realized, point to the wide scope for future explorations, expanding upon the present observations. PMID- 20301171 TI - Hydride transfer reactions via ion-neutral complex: fragmentation of protonated N benzylpiperidines and protonated N-benzylpiperazines in mass spectrometry. AB - An ion-neutral complex (INC)-mediated hydride transfer reaction was observed in the fragmentation of protonated N-benzylpiperidines and protonated N benzylpiperazines in electrospray ionization mass spectrometry. Upon protonation at the nitrogen atom, these compounds initially dissociated to an INC consisting of [RC(6)H(4)CH(2)](+) (R = substituent) and piperidine or piperazine. Although this INC was unstable, it did exist and was supported by both experiments and density functional theory (DFT) calculations. In the subsequent fragmentation, hydride transfer from the neutral partner to the cation species competed with the direct separation. The distribution of the two corresponding product ions was found to depend on the stabilization energy of this INC, and it was also approved by the study of substituent effects. For monosubstituted N-benzylpiperidines, strong electron-donating substituents favored the formation of [RC(6)H(4)CH(2)](+), whereas strong electron-withdrawing substituents favored the competing hydride transfer reaction leading to a loss of toluene. The logarithmic values of the abundance ratios of the two ions were well correlated with the nature of the substituents, or rather, the stabilization energy of this INC. PMID- 20301172 TI - Adsorption of proline and glycine on the TiO2(110) surface: a density functional theory study. AB - The optimal adsorption modes for the amino acids glycine and proline on the ideal TiO(2)(110) surface are investigated by using density functional theory (PBE) applying periodic boundary conditions. Binding modes with anionic acid moieties bridging two titanium atoms after transferring a proton to the surface are the most stable configurations for both molecules investigated-similar to previous results for carboxylic acids. In contrast to the latter compounds, amino acids can form hydrogen bonds via the amino group towards the surface-bound proton; this provides an additional stabilisation of 15-20 kJ mol(-1). Zwitterionic binding modes are less stable (by 10-20 kJ mol(-1)) and are less important for proline. Neutral modes are energetically even less favourable. Calculations of vibrational frequencies and core-level shifts complement the adsorption study and provide guidance for future experimental investigations. Control of the computational parameters is crucial for the derivation of accurate results. The layout and thickness of the slab model used are also shown to be decisive factors. Calculations with a different GGA-functional (PW91) provide very similar relative energies, although the absolute energies change by about 20 kJ mol(-1). Results derived with the hybrid functional PBE0 show an even greater stabilisation of the anionic binding modes with respect to the zwitterionic modes. A previously observed discrepancy between experimental and theoretical results for glycine could be solved, although the experimentally proposed free rotation of the C-C bond could not be reproduced. PMID- 20301173 TI - Determination of the vibrational density of states and emission spectrum of lutetium monoxide. PMID- 20301174 TI - In situ video-STM studies of adsorbate dynamics at electrochemical interfaces. AB - The dynamic behavior of individual adsorbates at electrochemical interfaces was studied directly by in situ high-speed scanning tunneling microscopy, using sulfur adsorbed on Cu(100) electrodes in 0.01 M HCl solution as an example. By dosing from diluted Na(2)S solutions S(ad) coverages of a few percent can be prepared, with the sulfur adsorbates occupying positions within the c(2x2) lattice of coadsorbed chloride. S(ad) tracer diffusion occurs via hopping between neighboring c(2x2) lattice sites at considerably higher rates than those of sulfur on Cu(100) under UHV conditions, indicating a pronounced influence of the electrochemical environment on the adsorbate surface dynamics. The diffusion barrier linearly increases by 0.5 eV per V with potential and is strongly affected by neighboring S(ad) and surface defects. The S(ad)-S(ad) interactions extend over approximately 7 A. They are repulsive between nearest-neighbor and attractive between next-nearest-neighbor sites, respectively, and result in significantly reduced diffusion barriers. S(ad) on the upper terrace side of steps are transiently trapped and exhibit lower diffusion rates, leading to the formation of small metastable p(2x2) domains. Attractive interactions between S(ad) and domain boundaries in the c(2x2) adlayer result in boundary pinning as well as transient trapping and enhanced diffusion of S(ad) along the boundary. PMID- 20301175 TI - Intermediates in the catalytic cycle of [NiFe] hydrogenase: functional spectroscopy of the active site. AB - The [NiFe] hydrogenase from the anaerobic sulphate reducing bacterium Desulfovibrio vulgaris Miyazaki F is an excellent model for constructing a mechanism for the function of the so-called 'oxygen-sensitive' hydrogenases. The present review focuses on spectroscopic investigations of the active site intermediates playing a role in the activation/deactivation and catalytic cycle of this enzyme as well as in the inhibition by carbon monoxide or molecular oxygen and the light-sensitivity of the hydrogenase. The methods employed include magnetic resonance and vibrational (FTIR) techniques combined with electrochemistry that deliver information about details of the geometrical and electronic structure of the intermediates and their redox behaviour. Based on these data a mechanistic scheme is developed. PMID- 20301176 TI - The conformations of amino acids on a gold(111) surface. AB - The interactions of amino acids with inorganic surfaces are of interest for biologists and biotechnologists alike. However, the structural determinants of peptide-surface interactions have remained elusive, but are important for a structural understanding of the interactions of biomolecules with gold surfaces. Molecular dynamics simulations are a tool to analyze structures of amino acids on surfaces. However, such an approach is challenging due to lacking parameterization for many surfaces and the polarizability of metal surfaces. Herein, we report DFT calculations of amino acid fragments in vacuo and molecular dynamics simulations of the interaction of all amino acids with a gold(111) surface in explicit solvent, using the recently introduced polarizable gold force field GolP. We describe preferred orientations of the amino acids on the metal surface. We find that all amino acids preferably interact with the gold surface at least partially with their backbone, underlining an unfolding propensity of gold surfaces. PMID- 20301177 TI - Site-specific DNA-controlled fusion of single lipid vesicles to supported lipid bilayers. AB - We investigate the Ca(2+)-triggered fusion of lipid vesicles site-selectively tethered to a DNA-modified supported lipid bilayer array, with the DNA strands designed such that hybridization occurs in a zipperlike fashion. Prior to the addition of Ca(2+), which is observed to induce docking and subsequent fusion (within 200 ms), the vesicles display lateral mobility determined by the number of tethers. Fusion is observed to require around ten DNA strands per vesicle, but does not occur at higher DNA coverage. However, despite the fact that fusion was restricted to occurring for vesicles tethered with around ten DNA strands, there is no correlation between single-vesicle diffusivity and fusogenicity. A possible scenario for the DNA-induced fusion machinery, consistent with these observations, is that prior to Ca(2+)-induced docking, the vesicles diffuse with a small number (2-4) of DNA tethers. Upon addition of Ca(2+), the vesicles dock, presumably due to bridging of lipid head groups. Fusion then occurs under conditions where 10-16 DNA tethers form and rearrange at the rim of the contact region between a docked vesicle and the SLB. The time required for this rearrangement, which may include both DNA hybridization and dehybridization during zipping, is expected to represent the observed docking and fusion time of less than 200 ms. PMID- 20301178 TI - Spatial distribution of acoustic cavitation bubbles at different ultrasound frequencies. AB - Images of sonoluminescence, sonophotoluminescence and sonochemiluminescence are recorded in order to semi-quantitatively compare the spatial distribution of the cavitation activity at three different ultrasound frequencies (170 kHz, 440 kHz and 700 kHz) and at various acoustic amplitudes. At all ultrasound frequencies investigated, the sonochemically active cavitation zones are much larger than the cavitation zones where sonoluminescence is observed. Also, the sonochemically active bubbles are observed at relatively lower acoustic amplitudes than that required for sonoluminescence bubbles to appear. The acoustic power required for the observation of the initial cavitation bubbles increases with an increase in the ultrasound frequency. The cavitation bubbles are observed relatively uniformly throughout the reactor at 170 kHz whereas they are located away from the transducer at the higher frequencies used in this study. While these observations highlight the complexities involved in acoustic cavitation, possible reasons for the observed results are discussed. PMID- 20301179 TI - Unusual chiral transfer in radical copolymerization of vinyl monomers bearing side-on p-terphenyl pendants. AB - Radical copolymerization of a chiral monomer, (+)-2,5-bis[4'-((S)-2 methylbutoxy)phenyl]styrene and an achiral monomer, 2,5-bis(4' hexyloxyphenyl)styrene, is carried out in anisole at 90 degrees C with benzoyl peroxide as the initiator. The resultant optically active helical copolymers show an unusual linear relationship between optical activity and composition, in sharp contrast with Green's "sergeants-and-soldiers" and "majority" rules. Analysis of the polarimetry, circular dichroism, and chain extension results suggest that the weak steric interaction between the propagation helical radical and the incoming monomer drove the copolymer chain to grow in a specific direction. Moreover, the helical macroinitiator is successfully used to induce the helix-sense-selective atom transfer radical polymerization of an achiral analogous monomer to yield optically-active block copolymers, which indicate a convenient way to prepare helical polymers with an excess screw sense from an achiral monomer by means of radical polymerization. PMID- 20301180 TI - A continuous-flow method for the generation of hydrogen from formic acid. PMID- 20301181 TI - Dealloying shows the way to new catalysts. PMID- 20301182 TI - Molecular dynamics simulations of MALDI: laser fluence and pulse width dependence of plume characteristics and consequences for matrix and analyte ionization. AB - Molecular dynamics simulations of matrix-assisted laser desorption/ionization were carried out to investigate laser pulse width and fluence effects on primary and secondary ionization process. At the same fluence, short (35 or 350 ps) pulses lead to much higher initial pressures and ion concentrations than longer ones (3 ns), but these differences do not persist because the system relaxes toward local thermal equilibrium on a nanosecond timescale. Higher fluences accentuate the initial disparities, but downstream differences are not substantial. Axial velocities of ions and neutrals are found to span a wide range, and be fluence dependent. Total ion yield is only weakly dependent on pulse width, and consistent with experimental estimates. Secondary reactions of matrix cations with analyte neutrals are efficient even though analyte ions are ablated in clusters of matrix. PMID- 20301183 TI - The kinematics of locomotion in caecilians: effects of substrate and body shape. AB - Caecilians are limbless amphibians that have radiated extensively in the tropics, and have evolved distinct cranial and postcranial specializations associated with a burrowing lifestyle. Some species are recognized as being surface active, whereas others are dedicated burrowers. Previous authors have demonstrated that some caecilians use a hydrostatic mechanism to generate burrowing forces which is dependent on the existence of skin-vertebral independence. It has been hypothesized that skin-vertebral independence may be lost in extremely elongated species, thus affecting their ability to burrow. Here, we use X-ray video to study the kinematics of locomotion in five species of caecilian differing in their degree of body elongation. Animals were filmed moving in or across different substrates imposing different functional demands on the locomotor system. Our data demonstrate that all species have the ability to perform internal concertina locomotion, but indicate differences between species in the kinematics of locomotion with more elongate species showing a smaller degree of skin-vertebral independence. In all species, locomotion was dependent on the substrate and species switched from using lateral undulation on the surface substrates to the use of whole body or internal concertina in wide and narrow tunnels, respectively. When burrowing in soil, all species used a combination of whole-body and internal concertina locomotion. Additional studies on the ability of different species to generate forces are needed to test whether the reduced skin-vertebral independence in elongate forms has resulted in a decreased ability to generate burrows. PMID- 20301185 TI - A study of the cesium cation bonding to carboxylate anions by the kinetic method and quantum chemical calculations. AB - Collision-induced dissociation (CID) of the Cs(+) heterodimer adducts of the nitrate anion (NO(3)(-)) and a variety of substituted benzoates (XBenz(-)) [(XBenz(-))(Cs(+))(NO(3)(-))](-) produces essentially nitrate and benzoate ions. A plot of the natural logarithm of their intensity ratio, ln[I (NO(3)( ))/I(XBenz(-))], versus the calculated cesium cation affinity (DFT B3LYP) of the substituted benzoate ions (equivalent to the enthalpy of heterolytic dissociation of the salt) is reasonably linear. This suggests that the kinetic method can be used as a source of data on the intrinsic interaction between the anionic and the cationic moieties in a salt. PMID- 20301184 TI - Mass spectrometry of fluorocarbon-labeled glycosphingolipids. AB - A method for generation of novel fluorocarbon derivatives of glycosphingolipids (GSLs) with high affinity for fluorocarbon phases has been developed, and their potential applications to mass spectrometry (MS)-based methodologies for glycosphingolipidomics have been investigated. Sphingolipid ceramide N-deacylase (SCDase) is used to remove the fatty acid from the ceramide moiety, after which a fluorocarbon-rich substituent (F-Tag) is incorporated at the free amine of the sphingoid. In initial trials, a neutral GSL, globotriaosylceramide (Gb(3)Cer), three purified bovine brain gangliosides, and four fungal glycosylinositol phosphorylceramides (GIPCs) were de-N-acylated, derivatized by prototype F-Tags, and recovered by solid phase extraction on fluorocarbon-derivatized silica (F SPE). The efficacy of SCDase treatment of GIPCs was here demonstrated for the first time. Compatibility with subsequent per-N,O-methylation was established for the F-tagged Gb(3) Cer and purified gangliosides, and extensive mass spectra (MS(1) and MS(2)) consistent with all of the expected products were acquired. The potential use of F-tagged derivatives for a comprehensive MS based profiling application was then demonstrated on a crude ganglioside mixture extracted from bovine brain. Finally, a simple trial in microarray format demonstrated fixation of F-tagged G(M1) ganglioside to a fluorous glass surface, with the glycan intact and available for interaction with a fluorescent derivative of cholera toxin B chain. The methods described thus provide a new avenue for rapid GSL recovery or cleanup, potentially compatible with a variety of platforms for mass spectrometric profiling and structure analysis, as well as parallel analysis of functional interactions. PMID- 20301189 TI - Abstracts of the Society of Hospital Medicine Annual Meeting. April 8-11, 2010. Washington, DC, USA. PMID- 20301192 TI - Atomic force microscopy study on chlorpromazine-induced morphological changes of living HeLa cells In Vitro. AB - Chlorpromazine (CPZ)-induced morphological changes of living human cervical carcinoma cells were investigated by atomic force microscopy in near physiological condition. The results showed that the cell morphology changed visibly with time in the presence of CPZ (>21 microM). The cell membrane shrank gradually and detached finally from the substrate. After being treated with CPZ for 50 min, the cell volume increased by about 27.6% while its projective area (cell adhered to the substrate) decreased by about 12%. The mechanism was also discussed. PMID- 20301193 TI - Activation of human bronchial epithelial cells by inflammatory cytokines IL-27 and TNF-alpha: implications for immunopathophysiology of airway inflammation. AB - Interleukin (IL)-27 is a member of IL-6/IL-12 family cytokines produced by antigen-presenting cells in immune responses. IL-27 can drive the commitment of naive T cells to a T helper type 1 (Th1) phenotype and inhibit inflammation in later phases of infection. Human bronchial epithelial cells have been shown to express IL-27 receptor complex. In this study, we investigated the in vitro effects of IL-27, alone or in combination with inflammatory cytokine tumor necrosis factor (TNF)-alpha on the pro-inflammatory activation of human primary bronchial epithelial cells and the underlying intracellular signaling mechanisms. IL-27 was found to enhance intercellular adhesion molecule 1 (ICAM-1) expression on the surface of human bronchial epithelial cells, and a synergistic effect was observed in the combined treatment of IL-27 and TNF-alpha on the expression of ICAM-1. Although IL-27 did not alter the basal IL-6 secretion from bronchial epithelial cells, it could significantly augment TNF-alpha-induced IL-6 release. These synergistic effects on the up-regulation of ICAM-1 and IL-6 were partially due to the elevated expression of TNF-alpha receptor (p55TNFR) induced by IL-27. Further investigations showed that the elevation of ICAM-1 and IL-6 in human bronchial epithelial cells stimulated by IL-27 and TNF-alpha was differentially regulated by phosphatidylinositol 3-OH kinase (PI3K)-Akt, p38 mitogen-activated protein kinase, and nuclear factor-kappaB pathways. Our results therefore provide a new insight into the molecular mechanisms involved in airway inflammation. PMID- 20301195 TI - Lipophilic cationic drugs increase the permeability of lysosomal membranes in a cell culture system. AB - Lysosomes accumulate many drugs several fold higher compared to their extracellular concentration. This mechanism is believed to be responsible for many pharmacological effects. So far, uptake and release kinetics are largely unknown and interactions between concomitantly administered drugs often provoke mutual interference. In this study, we addressed these questions in a cell culture model. The molecular mechanism for lysosomal uptake kinetics was analyzed by live cell fluorescence microscopy in SY5Y cells using four drugs (amantadine, amitriptyline, cinnarizine, flavoxate) with different physicochemical properties. Drugs with higher lipophilicity accumulated more extensively within lysosomes, whereas a higher pK(a) value was associated with a more rapid uptake. The drug induced displacement of LysoTracker was neither caused by elevation of intra lysosomal pH, nor by increased lysosomal volume. We extended our previously developed numerical single cell model by introducing a dynamic feedback mechanism. The empirical data were in good agreement with the results obtained from the numerical model. The experimental data and results from the numerical model lead to the conclusion that intra-lysosomal accumulation of lipophilic xenobiotics enhances lysosomal membrane permeability. Manipulation of lysosomal membrane permeability might be useful to overcome, for example, multi-drug resistance by altering subcellular drug distribution. PMID- 20301194 TI - Sorafenib combined vitamin K induces apoptosis in human pancreatic cancer cell lines through RAF/MEK/ERK and c-Jun NH2-terminal kinase pathways. AB - Apoptosis has been shown to be induced by many agents, including the clinically useful Sorafenib and K vitamins (VKs). Since few agents have activity against pancreas cancer cell growth, we evaluated the role of naturally occurring K vitamins and Sorafenib both independently and together on the growth in culture of pancreas adenocarcinoma cell lines, including PL-5, PANC-1, and MIA PaCa-2. We found that when a K vitamin was combined with Sorafenib, the dose of Sorafenib required for growth inhibition was substantially reduced. Furthermore, growth could be inhibited at doses of each VK plus Sorafenib in combination that were ineffective when used alone. This effect was seen using vitamins K1, K2, and K5. The combination of VK1 plus Sorafenib-induced apoptosis, as determined by both FACS and TUNEL staining. Phospho-ERK and Bcl-2 levels were decreased, but not levels of other bcl-2 family members. Cleavage of caspases 3 and 8, PARP and Bid were all induced by this combination. Vitamin K1 plus Sorafenib combination also resulted in elevated levels of activated c-Jun N-terminal kinase (JNK) and its substrates c-Jun and FasL. JNK inhibition partly antagonized the induction of apoptosis. Thus, combination VK1 plus Sorafenib strongly induced growth inhibition and apoptosis in pancreas cancer cells, involving both inhibition of the RAF/MEK/ERK pathway as well as activation of the JNK, c-Jun and FasL apoptotic pathway. Since both agents are available for human use, the combination is attractive for evaluation against pancreas cancer growth in vivo. PMID- 20301197 TI - Estrogen regulated expression of the p21 Waf1/Cip1 gene in estrogen receptor positive human breast cancer cells. AB - The cyclin-dependent kinase inhibitor protein p21(Waf1/Cip1) is a potent tumor suppressor. Here, we demonstrate that estradiol regulates the p21(Waf1/Cip1) gene. Estradiol induces p21(Waf1/Cip1) mRNA expression within 30-60 min independent of new protein synthesis in the estrogen receptor alpha (ER alpha) positive human breast cancer cell line MCF-7. Similar to other estradiol responsive promoters, the p21(Waf1/Cip1) upstream promoter region has several estrogen response element (ERE) half-sites nestled in AP-1 binding sites, which are positioned upstream to Sp1 binding sites. Using the chromatin immunoprecipitation (ChIP) assay, we show that estradiol stimulation resulted in the recruitment of transcription factors ER alpha, Sp1, and Sp3 to the p21(Waf1/Cip1) upstream promoter element. The Sp1 inhibitor mithramycin A abrogated Sp1, and to a lesser extent Sp3 binding, and markedly reduced the estradiol stimulated p21(Waf1/Cip1) gene expression. However, ER alpha binding was not affected in the mithramycin A and estradiol treated cells. On closer examination of the half-site ERE/AP-1 sites upstream to the Sp1 sites in a separate ChIP experiment, we found a pronounced association of ER alpha upon estradiol treatment compared to almost negligible binding of Sp1 or Sp3. Together these studies provide evidence that ER alpha is recruited to the half-site ERE/AP 1 sites in the p21(Waf1/Cip1) upstream promoter element. Although Sp1/Sp3 is not involved in the recruitment of ER alpha to the promoter, Sp1 is necessary for estrogen-induced p21(Waf1/Cip1) promoter activity. PMID- 20301198 TI - Protein-protein interactions involving IKKgamma (NEMO) that promote the activation of NF-kappaB. AB - Inhibitor of kappaB kinase (IKK) gamma (IKKgamma), also referred to as nuclear factor kappaB (NF-kappaB) essential modulator (NEMO), is an important regulatory component of the IKK complex. The IKK complex is a signalosome that catalyzes the inducible phosphorylation of IkappaB proteins, which is a key step that leads to the activation of NF-kappaB. The exact functions of IKKgamma (NEMO) as part of the IKK complex have not yet been fully elucidated. This mini-review covers 16 proteins that have been reported to bind to IKKgamma and lead to the enhancement of the activities of the IKK complex, thus resulting in NF-kappaB activation. The major mechanisms by which these interactions are mediated involve the recognition of ubiquitinated upstream signaling components by IKKgamma or the modification of IKKgamma itself by ubiquitination. Additional mechanisms include the sumoylation or phosphorylation of IKKgamma and the modification of the tertiary or quaternary structure of IKKgamma. PMID- 20301196 TI - Promotion of cell spreading and migration by vascular endothelial-protein tyrosine phosphatase (VE-PTP) in cooperation with integrins. AB - Vascular endothelial-protein tyrosine phosphatase (VE-PTP) is a receptor-type protein tyrosine phosphatase with a single catalytic domain in its cytoplasmic region and multiple fibronectin type III-like domains in its extracellular region. VE-PTP is expressed specifically in endothelial cells and is implicated in regulation of angiogenesis. The molecular basis for such regulation by VE-PTP has remained largely unknown, however. We now show that forced expression of VE PTP promoted cell spreading as well as formation of lamellipodia and filopodia in cultured fibroblasts plated on fibronectin. These effects of VE-PTP on cell morphology required its catalytic activity as well as activation of integrins and Ras. In addition, VE-PTP-induced cell spreading and lamellipodium formation were prevented by inhibition of Src family kinases or of Rac or Cdc42. Indeed, forced expression of VE-PTP increased the level of c-Src phosphorylation at tyrosine 416. Moreover, the VE-PTP-induced changes in cell morphology were suppressed by expression of dominant negative forms of FRG or Vav2, both of which are guanine nucleotide exchange factors for Rho family proteins and are activated by tyrosine phosphorylation. Forced expression of VE-PTP also enhanced fibronectin-dependent migration of cultured fibroblasts. Conversely, depletion of VE-PTP by RNA interference in human umbilical vein endothelial cells or mouse endothelioma cells inhibited cell spreading on fibronectin. These results suggest that VE-PTP, in cooperation with integrins, regulates the spreading and migration of endothelial cells during angiogenesis. PMID- 20301199 TI - Facial synkinesis after experimental compression of the facial nerve comparing intratemporal and extratemporal lesions. AB - OBJECTIVES/HYPOTHESIS: The anatomical configuration of the facial nerve differs greatly between the intratemporal and extratemporal portions. The purpose of this study was to investigate the incidence of facial synkinesis and misdirection on clamping the facial nerve at the intratemporal or extratemporal portion of the facial nerve in guinea pigs. STUDY DESIGN: Experimental study. METHODS: In 16 guinea pigs, the facial nerve was clamped with microsurgical needle forceps at either the extratemporal (group A) or intratemporal (group B) segment. Facial nerve function was evaluated 1 week postoperatively using electroneurography (ENoG), and the incidence of facial synkinesis was evaluated 15 weeks postoperatively using an evoked blink reflex test. Fifteen weeks postoperatively, two retrograde fluorescent tracers (Dil [1-1'-dioctodecyl-3,3,3',3'-tetramethyl indocarbocyanine perchlorate] and True Blue) were injected into the facial muscles to observe reorganization of the facial nucleus. RESULTS: No significant difference in the ENoG threshold was observed between groups A and B. In group A, none of the animals developed facial synkinesis and the somatotopic organization of the facial nucleus was not disturbed. In contrast, synkinesis occurred and the somatotopic organization was disturbed in group B. CONCLUSIONS: A lack of funicular structure within the intratemporal facial nerve increases the possibility of misdirected regenerating axons and synkinesis. PMID- 20301200 TI - PHR1 is a vesicle-bound protein abundantly expressed in mature olfactory neurons. AB - OBJECTIVES/HYPOTHESIS: To characterize the role of Phr1, a gene highly expressed in primary sensory neurons where it encodes an integral membrane protein with an N-terminal pleckstrin homology domain and a C-terminal transmembrane domain, in the olfactory system. METHODS: We studied the immunelocalization of the PHR1 protein in mouse olfactory epithelium both at steady state and during regeneration following methyl bromide (MeBr) exposure using scanning confocal microscopy. Additionally, we examined the electrophysiologic role of Phr1 in olfaction and short-term olfactory adaptation. RESULTS: We found that PHR1 is abundantly and specifically expressed in olfactory neurons. It is widely distributed in punctate, vesiculated organelles throughout the cell bodies, axons, and glomeruli of primary olfactory neurons but is specifically excluded from the olfactory cilia. In the regenerating olfactory epithelium, PHR1 expression appears at 14 days following MeBr ablation coinciding with the onset of olfactory neuron maturity. Despite the abundant and specific expression throughout the olfactory neurons, mice lacking Phr1 did not exhibit differences in the distribution of the components of olfactory signal transduction system, the rate of olfactory regeneration following MeBr exposure, olfactory function, or short-term adaptation to odors. CONCLUSIONS: Phr1 is widely and abundantly expressed throughout mature olfactory neurons and other primary sensory neurons, but its absence does not appear to affect olfactory morphology, regeneration, sensory function, or adaptation. The exact function of Phr1 remains to be discovered. PMID- 20301202 TI - First trimester maternal serum placental growth factor in trisomy 21 pregnancies. AB - OBJECTIVE: To examine placental growth factor (PlGF) levels in first trimester maternal serum in trisomy 21 pregnancies and to investigate the potential value of PlGF in a first trimester screening test. METHODS: First trimester maternal serum from 70 trisomy 21 cases and 375 euploid controls were retrospectively analyzed for PlGF using a DELFIA Xpress immunoassay platform. Results were expressed as multiples of medians (MoM) for comparison. RESULTS: PlGF levels were significantly decreased in pregnancies with trisomy 21, 0.76 MoM versus 0.98 MoM in controls. Inclusion of PlGF into the first trimester combined test [maternal age, pregnancy associated plasma protein-A (PAPP-A), free-beta human chorionic gonadotrophin (beta-hCG) and nuchal translucency] would increase the detection rate by 0.5% at a 5% false positive rate. CONCLUSION: PlGF at 11 weeks to 13 weeks 6 days has the potential to be included as a marker for the detection of pregnancies with trisomy 21. PMID- 20301201 TI - Epitope mapping of function-blocking monoclonal antibody CM6 suggests a "weak" integrin binding site on the laminin-332 LG2 domain. AB - Laminin-332 (Ln-332) is an extracellular matrix molecule that regulates cell adhesion, spreading, and migration by interaction with cell surface receptors such as alpha3beta1 and alpha6beta4. Previously, we developed a function-blocking monoclonal antibody against rat Ln-332, CM6, which blocks hemidesmosome assembly induced by Ln-332-alpha6beta4 interactions. However, the location of its epitope on Ln-332 has remained unclear. In this study, we show that the CM6 epitope is located on the laminin G-like (LG)2 module of the Ln-332 alpha3 chain. To specify the residues involved in this epitope, we produced a series of GST-fused alpha3 LG2 mutant proteins in which rat-specific acids were replaced with human acids by a site-directed mutagenesis strategy. CM6 reactivity against these proteins showed that CM6 binds to the (1089)NERSVR(1094) sequence of rat Ln-332 LG2 module. In a structural model, this sequence maps to an LG2 loop sequence that is exposed to solvent according to predictions, consistent with its accessibility to antibody. CM6 inhibits integrin-dependent cell adhesion on Ln-332 and inhibits cell spreading on both Ln-332 and recombinant LG2 (rLG2; but not rLG3), suggesting the presence of an alpha3beta1 binding site on LG2. However, we were unable to show that rLG2 supports adhesion in standard assays, suggesting that LG2 may contain a "weak" integrin binding site, only detectable in spreading assays that do not require washes. These results, together with our previous findings, indicate that binding sites for alpha3beta1 and alpha6beta4 are closely spaced in the Ln-332 LG domains where they regulate alternative cell functions, namely adhesion/migration or hemidesmosome anchoring. PMID- 20301203 TI - Trifluoromethylated (tetrahydropyrrolo) quinazolinones by a new three-component reaction and facile assignment of the regio- and stereoisomers formed by NMR spectroscopy. AB - A new three-component cyclisation reactions of methyl 3,3,3-trifluoropyruvate, 2 aminobenzylamine and oxo compounds afforded tetrahydropyrroloquinazolinones of the types 4 and 5 as mixtures of regio- and stereoisomers. Whereas standard 1D NMR spectroscopy was used for a facile assignment of the cyclization regioisomers, a combination of homo (proton-proton) and heteronuclear (proton fluorine) NOE experiments allowed the determination of the relative configuration on stereogenic centres. The structure of some compounds was also confirmed by the X-ray diffraction. Adaptation of the 1D double-pulsed field-gradient spin-echo NOE for a heteronuclear case is presented. PMID- 20301204 TI - Successful photocoagulation on both sides of inter-twin membrane for twin-twin transfusion syndrome in a case of iatrogenic septostomy after an amnioreduction. PMID- 20301205 TI - Glycolysis links p53 function with NF-kappaB signaling: impact on cancer and aging process. AB - In 1930, Otto Warburg observed that cancer cells produce an increased amount of their energy through aerobic glycolysis and subsequently, this was called the Warburg effect. During aging, the capacity for mitochondrial respiration clearly declines and aerobic glycolysis appears to compensate for the deficiency in oxidative metabolism. This shift in energy production, both in aging and cancer, could protect from the toxic effects of oxygen free radicals whereas increased glycolysis can have adverse effects. It was recently demonstrated that the glycolysis-linked protein O-glycosylation can potentiate the catalytic activity of IKK beta and subsequently trigger NF-kappaB signaling. It seems that tumor suppressor oncogene p53 has an important role in the regulation of protein O glycosylation since p53 is a potent inhibitor of glycolysis, for example, via TIGAR protein expression. Aging is known to repress the function of p53 and this could enhance glycolysis and NF-kappaB signaling. We will discuss the role of p53 in the regulation of glycolysis-dependent activation of NF-kappaB signaling in both cancer and aging process. PMID- 20301206 TI - Hepatitis B virus replication in primary macaque hepatocytes: crossing the species barrier toward a new small primate model. AB - The development of new anti-hepatitis B virus (HBV) therapies, especially immunotherapeutic approaches, has been limited by the lack of a primate model more accessible than chimpanzees. We have previously demonstrated that sylvanus and cynomolgus macaques are susceptible to in vivo HBV infection after intrahepatic HBV DNA inoculation. In this study, we evaluated the susceptibility of primary macaque hepatocytes (PMHs) to HBV infection with a highly efficient HBV genome-mediated transfer system via a recombinant baculovirus (Bac-HBV). Freshly prepared PMHs, isolated from macaque liver tissue by collagenase perfusion, were transduced with Bac-HBV, and intermediates of replication were followed for 9 days post-transduction. Evidence of HBV replication (hepatitis B surface antigen secretion, viral DNA, RNA, and covalently closed circular DNA) was detected from day 1 to day 9 post-transduction. HBV markers were dose dependent and still detectable at a multiplicity of infection of 10. Importantly, transduced PMHs secreted all typical forms of HBV particles, as evidenced by a cesium chloride gradient as well as transmission electron microscopy. Furthermore, the Toll-like receptor 9 (TLR9) ligand was used to stimulate freshly prepared macaque peripheral blood mononuclear cells to generate TLR9-induced cytokines. We then demonstrated the antiviral effects of both TLR9-induced cytokines and nucleoside analogue (lamivudine) on HBV replication in transduced PMHs. CONCLUSION: Baculovirus-mediated genome transfer initiated a full HBV replication cycle in PMHs; thus highlighted both the baculovirus efficiency in crossing the species barrier and macaque susceptibility to HBV infection. Moreover, our results demonstrate the relevance of thus system for antiviral compound evaluations with either nucleoside analogues or inhibitory cytokines. Cynomolgus macaques are readily available, are immunologically closely related to humans, and may therefore represent a promising model for the development of new immunotherapeutic strategies. PMID- 20301207 TI - Cytological diagnosis of actinomycosis and eumycetoma: a report of two cases. AB - Mycetoma and actinomycosis are common in tropical countries and are increasingly diagnosed in other parts of the world due to rapid mobilization of the population. They are usually diagnosed on histopathology. There is very limited data on the role of fine-needle aspiration cytology (FNAC) in diagnosing these lesions. We report here two cases: one of eumycetoma and the other of an actinomycosis that were reliably diagnosed with FNAC. The cytological features were similar to histopathology features and differentiated eumycetoma and actinomycosis. FNAC is a rapid, simple and inexpensive outpatient procedure that helps in rapid diagnosis. PMID- 20301208 TI - Intrathyroidal oncocytic parathyroid adenoma: a diagnostic pitfall on fine-needle aspiration. AB - Oncocytic parathyroid adenoma is a rarely seen benign neoplasm of the parathyroid and intrathyroidal location of this lesion is also uncommon. It can be easily misdiagnosed as Hurthle cell thyroid neoplasm on fine-needle aspiration (FNA). Here, an intrathyroidal oncocytic parathyroid adenoma in a 32-year-old male is reported. Ultrasonography showed a nodule 2 cm in largest diameter in the left thyroid lobe. FNA revealed cellular smears containing monotonous oncocytic cells arranged in monolayered sheets, pseudopapillary structures and clusters within a rich vascular network. The case was reported as "suspicious for Hurthle cell thyroid neoplasm" on FNA. Frozen section examination showed intrathyroidal oncocytic parathyroid adenoma with a rim of normal parathyroid tissue. The diagnosis was also confirmed with immunohistochemical stains (TTF-1, PTH, thyroglobulin) performed on permanent sections. Cytopathologic features of oncocytic parathyroid adenoma and Hurthle cell thyroid neoplasm are similar. It is important to keep oncocytic parathyroid adenoma in mind in the differential diagnosis of Hurthle cell thyroid neoplasm. Prior knowledge of clinical, radiological and laboratory data will avoid wrong cytopathologic diagnosis. PMID- 20301209 TI - Cytopathological features of warty (condylomatous) carcinoma of the penis: a case report and distinction from other verruciform penile tumors. AB - Warty (condylomatous) carcinoma (WC) is a rare specific variant of invasive squamous cell carcinoma that shows hybrid features of condyloma with invasive cell carcinoma. As compared with conventional squamous cell carcinoma, WC tends to run a less aggressive clinical course. A case is presented here in which squash smears of a penile foreskin tumor in a 65-year-old male revealed small cohesive clusters and sheets of tumor cells in papillary configurations. The neoplastic cells were polygonal to elongated and contained oval nuclei, coarse chromatin pattern, and distinct nucleoli. Nuclear pleomorphism and loss of nuclear polarity were observed. Characteristically, there were also many koilocytes demonstrating mild to moderate nuclear atypia and perinuclear cytoplasmic halos. A cytologic diagnosis of a verruciform penile tumor was suggested. Histologic examination of the tumor showed a hyper-parakeratotic arborizing papillomatous growth with thin fibrovascular cores and the tips were variably rounded or tapered. Obvious koilocytic cytopathic change, nuclear pleomorphism, and focal stromal invasion were observed. Immunohistochemically, the tumor cells showed diffuse and strong membranous staining for cytokeratin (AE1/AE3) while the MIB-1 and p53 immunoreactive cells were confined to the basal areas of the papillae. No lymphovascular invasion was detected in D2-40 or elastic Van-Gieson stains. On the basis of the overall features, we confirmed a final diagnosis of penile WC. We demonstrated here for the first time the cytopathological features of penile WC with emphasis on differential diagnostic considerations. PMID- 20301210 TI - Large pulmonary cryptococcoma and cryptococcal meningitis in an immunocompetent patient: a case report. AB - Pulmonary cryptococcoma is a life threatening mycosis and is an unusual disease for immunocompetent individuals. Herein we report a case of large pulmonary cryptococcoma associated with cryptococcal meningitis, presenting radiologically as a lung mass in right upper lobe, in a previously healthy, HIV negative, immunocompetent young individual. Since cryptococcosis continues to be an important infection in HIV negative patients and is associated with substantial overall and cause-specific mortality, the need for consideration of this entity in the differential diagnosis of a lung mass is emphasized. PMID- 20301211 TI - Elevated expression of SOX9 is related with the progression of gastric carcinoma. AB - To investigate the SOX9 expression and its effects on promoting invasion and metastasis in the primary gastric adenocarcinomas. One hundred and eighty six patients with primary gastric adenocarcinomas who underwent surgery between 2002 and 2006 were classified as low, intermediate, and high SOX9 expression groups by immunohistochemistry (IHC). Our IHC performance showed that SOX9 was lowly expressed in lower crypt of the normal epithelium adjacent to the tumor, and SOX9 expression was also observed in the intestinal metaplastic epithelium, but no SOX9 expression was detected in the surface epithelium. The stronger SOX9 expression was observed in the T3-T4 group than in the T1-T2 group, and there was a significant difference between the two groups (P < 0.0005). The SOX9 expression was correlated with the lymph node metastasis, and it showed significant between N0, N1, N2, and N3 groups (P < 0.0005). Similar to the lymph node metastasis classification, the SOX9 expression was also related to the tumor staging. From the stage Ia-Ib to stage II-IIIa and stage IIIb-IV, the SOX9 expression was elevated and the difference was significant (P < 0.0005). On the contrary, the SOX9 expression was not related to the histological classification (P > 0.05). Also the SOX9 expression showed no significance in patient age (P > 0.05). The SOX9 is overexpressed in the advanced stage of gastric carcinoma. SOX9 is related to the tumor progression though promoting invasion and metastasis, probably via enhancing the adhesion between the tumor cells and matrix or vessels which facilitates the tumor cells metastasis. PMID- 20301212 TI - Papanicolaou stain may not be necessary in majority of head and neck fine-needle aspirations: evidence from a correlation study between Diff-Quik-based onsite diagnosis and final diagnosis in 287 head and neck fine-needle aspirations. AB - Fine-needle aspiration (FNA) is a useful tool for immediate assessment of palpable lesions, especially in the head and neck region. The objective of this study is to evaluate the degree of correlation between Diff-Quik-based onsite diagnosis (OD) and final diagnosis (FD) and further improve the efficiency of FNA practice. Two hundred and eighty-seven cytopathologist-performed FNAs from the head and neck region were evaluated. Number of passes, number and type of slides and correlation (agreement, modified final diagnosis and disagreement) between OD and FD were evaluated. Among 287 FNAs, the average number of passes per FNA case was 2 (range, 1-5&.rpar;). The mean number of slides reviewed per case was 5 including 2 Diff-Quik (D-Q)-stained slides, 2 Papanicolaou (Pap)-stained slides, and 1 cell block (CB)/1 cytospin (Cy). 247 of 287 (86%) cases showed agreement between OD and FD. FD on 36 out of 287 cases (12.5%) was slightly modified or refined after reviewing additional slides. A major diagnostic discrepancy was noted in four cases (1.5%), three of which were classified as squamous cell carcinoma on final diagnosis, and confirmed on surgical follow-up. Accurate diagnosis can be achieved in the majority (86%) of head and neck FNAs based on immediate examination of D-Q stained slides alone. In a small number of cases (12.5%), reviewing additional slides may refine the final diagnosis. In rare cases, especially cystic squamous lesions, Pap-stained slides appeared to be helpful. It is plausible to use D-Q-stained slides alone with most head and neck FNAs in order to provide more cost effective and efficient triaging and patient management. PMID- 20301213 TI - Cytological findings of mixed squamous cell and glandular papilloma in the lung. AB - Pulmonary mixed squamous cell and glandular papilloma is an extremely rare neoplasm. This is the first cytological report of such a rare neoplasm. A 59-year old Japanese man was admitted to the hospital complaining of a persistent cough and bloody sputum. A bronchial endoscopic examination revealed an endobronchial polypoid tumor. Upon bronchial brush cytology by Papanicolaou stain, squamous dysplasia showing mild atypia was suspected. The smears showed moderate cellularity with singly scattered cells or loose clusters of cells, consisting of squamous cells and a few columnar cells. Nuclei of the squamous cells showed mild atypia, but there was no nuclear atypia of the columnar cells. Upon intraoperative pathological examination by frozen section, pulmonary mixed squamous cell and glandular papilloma was suspected. Intraoperative imprint cytology by Ultrafast Papanicolaou stain showed a few differences in comparison with bronchial brush cytology, which were thought to be due to differences in obtaining cytological specimens or the steps prior to the staining. The patient underwent a segmentectomy of the left lung. Histopathological diagnosis confirmed a mixed squamous cell and glandular papilloma. The postoperative course has been uneventful for 5 years after surgery. It was thought that cytology was diagnostically inadequate on its own in the present case. However, mixed squamous cell and glandular papilloma must be considered as another type of pulmonary tumor in cytological preparations, especially in a case showing endobronchial papillary growth by bronchoscopy. PMID- 20301214 TI - beta-Sheet aggregation of kisspeptin-10 is stimulated by heparin but inhibited by amphiphiles. AB - The murine 10-residue neurohormone kisspeptin (YNWNSFGLRY) is an important regulator of reproductive behavior and gonadotrophin secretion. It is known to form a random coil in solution, but undergoes a structural change in the presence of membranes although the nature of this change is not fully determined. The peptide's conformational versatility raises the question whether it is also able to form ordered aggregates under physiological conditions, which might be relevant as a storage mechanism. Here we show that heparin induces kisspeptin to form beta-sheet rich amyloid aggregates both at neutral (pH 7.0) and slightly acidic (pH 5.2) conditions. Addition of heparin leads to aggregation after a certain lag phase, irrespective of the time of addition of heparin, indicating that heparin is needed to facilitate the formation of fibrillation nuclei. Aggregation is completely inhibited by submicellar concentrations of zwitterionic and anionic surfactants. Unlike previous reports, our NMR data do not indicate persistent structure in the presence of zwitterionic surfactant micelles. Thus kisspeptin can aggregate under physiologically relevant conditions provided heparin is present, but the process is highly sensitive to the presence of amphiphiles, highlighting the very dynamic nature of the peptide conformation and suggesting that kisspeptin aggregation is a biologically regulatable process. PMID- 20301215 TI - Conformations and properties of the L-tryptophyl-containing peptides in solution, depending on the pH--theoretical study vs. experiments. AB - The conformational preference and electronic properties of three L-tryptophyl containing dipeptides, i.e., glycyl-L-tryptophane (H-Gly-Trp-OH), L-alanyl-L tryptophane (H-Ala-Trp-OH), and L-methionyl-L-tryptophane (L-Met-Trp-OH) in solution depending on the pH of the media are studied both theoretically and experimentally. The effect of the protonation of the COO(-) and deprotonation of the NH3+ as well as the alkaline hydrolysis of the amide fragment in a strong basic media on the electronic spectra are discussed. Ab initio and density functional theory (DFT) methods as well as the time-dependent DFT (TD-DFT) method as a function of the basis set are performed with a view to obtain the geometry and electronic properties of all of the species as well as the intermediate, obtained in the alkaline hydrolysis mechanism. PMID- 20301216 TI - Widespread distribution of knockdown resistance mutations in the bed bug, Cimex lectularius (Hemiptera: Cimicidae), populations in the United States. AB - We previously reported high deltamethrin resistance in bed bugs, Cimex lectularius, collected from multiple areas of the United States (Romero et al., 2007). Recently, two mutations, the Valine to Leucine mutation (V419L) and the Leucine to Isoleucine mutation (L925I) in voltage-gated sodium channel alpha subunit gene, had been identified to be responsible for knockdown resistance (kdr) to deltamethrin in bed bugs collected from New York (Yoon et al., 2008). The current study was undertaken to investigate the distribution of these two kdr mutations in 110 bed bug populations collected in the United States. Out of the 17 bed bug populations that were assayed for deltamethrin susceptibility, two resistant populations collected in the Cincinnati area and three deltamethrin susceptible lab colonies showed neither of the two reported mutations (haplotype A). The remaining 12 populations contained L925I or both V419L and L925I mutations in voltage-gated sodium channel alpha-subunit gene (haplotypes B&C). In 93 populations that were not assayed for deltamethrin susceptibility, 12 contained neither of the two mutations (haplotype A) and 81 contained L925I or V419L or both mutations (haplotypes B-D). Thus, 88% of the bed bug populations collected showed target-site mutations. These data suggest that deltamethrin resistance conferred by target-site insensitivity of sodium channel is widely spread in bed bug populations across the United States. PMID- 20301217 TI - Heparan sulfate in lung morphogenesis: The elephant in the room. AB - Heparan sulfate (HS) is a structurally complex polysaccharide located on the cell surface and in the extracellular matrix, where it participates in numerous biological processes through interactions with a vast number of regulatory proteins such as growth factors and morphogens. HS is crucial for lung development; disruption of HS synthesis in flies and mice results in a major aberration of airway branching, and in mice, it results in neonatal death as a consequence of malformed lungs and respiratory distress. Epithelial-mesenchymal interactions governing lung morphogenesis are directed by various diffusible proteins, many of which bind to, and are regulated by HS, including fibroblast growth factors, sonic hedgehog, and bone morphogenetic proteins. The majority of research into the molecular mechanisms underlying defective lung morphogenesis and pulmonary pathologies, such as bronchopulmonary dysplasia and pulmonary hypoplasia associated with congenital diaphragmatic hernia (CDH), has focused on abnormal protein expression. The potential contribution of HS to abnormalities of lung development has yet to be explored to any significant extent, which is somewhat surprising given the abnormal lung phenotype exhibited by mutant mice synthesizing abnormal HS. This review summarizes our current understanding of the role of HS and HS-binding proteins in lung morphogenesis and will present in vitro and in vivo evidence for the fundamental importance of HS in airway development. Finally, we will discuss the future possibility of HS-based therapeutics for ameliorating insufficient lung growth associated with lung diseases such as CDH. PMID- 20301219 TI - Extracellular matrix provides an optimal niche for the maintenance and propagation of mesenchymal stem cells. AB - Relatively little is known about the cellular and molecular mechanisms underlying the control of mesenchymal stem cell (MSC) proliferation, differentiation, and survival. This presents difficulties in following and characterizing cells along the lineage because of our inability to isolate and obtain a sufficient number of homogeneous MSCs using current culture systems for in vitro expansion. Adjusting the cellular machinery to allow greater proliferation can lead to other unwanted outcomes, such as unmanageable precancerous changes, or differentiation down an undesired pathway. Recently, it has become increasingly evident that the extracellular matrix (ECM) is an important component of the cellular niche in a tissue, supplying critical biochemical and physical signals to initiate and sustain cellular functions. Indeed, it is very doubtful that the intricate and highly ordered nature of the ECM could be reproduced with synthetic or purified components. This review cites evidence that supports an alternative approach for maintenance of MSCs by simulating in vitro the bone marrow ECM, where MSCs reside in vivo, and discusses the potential mechanisms whereby the ECM regulates the exposure of cells to growth factors that subsequently control MSC replication and differentiation, and also how the ECM provides unique cues that govern the lineage specification and differentiation of MSCs. PMID- 20301220 TI - Basement membranes in development and disease. AB - Basement membranes (BMs) are specializations of the extracellular matrix that act as key mediators of development and disease. Their sheet like protein matrices typically serve to separate epithelial or endothelial cell layers from underlying mesenchymal tissues, providing both a biophysical support to overlying tissue as well as a hub to promote and regulate cell-cell and cell-protein interactions. In the latter context, the BM is increasingly being recognized as a mediator of growth factor interactions during development. In this review, we discuss recent findings regarding the structure of the BM and its roles in mediating the normal development of the embryo, and we examine congenital diseases affecting the BM which impact embryonic development and health in later life. PMID- 20301221 TI - The role of mechanical signals in regulating chondrogenesis and osteogenesis of mesenchymal stem cells. AB - It is becoming increasingly clear that mesenchymal stem cell (MSC) differentiation is regulated by mechanical signals. Mechanical forces generated intrinsically within the cell in response to its extracellular environment, and extrinsic mechanical signals imposed upon the cell by the extracellular environment, play a central role in determining MSC fate. This article reviews chondrogenesis and osteogenesis during skeletogenesis, and then considers the role of mechanics in regulating limb development and regenerative events such as fracture repair. However, observing skeletal changes under altered loading conditions can only partially explain the role of mechanics in controlling MSC differentiation. Increasingly, understanding how epigenetic factors, such as the mechanical environment, regulate stem cell fate is undertaken using tightly controlled in vitro models. Factors such as bioengineered surfaces, substrates, and bioreactor systems are used to control the mechanical forces imposed upon, and generated within, MSCs. From these studies, a clearer picture of how osteogenesis and chondrogenesis of MSCs is regulated by mechanical signals is beginning to emerge. Understanding the response of MSCs to such regulatory factors is a key step towards understanding their role in development, disease and regeneration. PMID- 20301218 TI - Tissue-dependent induction of apoptosis by matrix metalloproteinase stromelysin-3 during amphibian metamorphosis. AB - Matrix metalloproteinases (MMPs) are a superfamily of Zn(2+)-dependent proteases that are capable of cleaving the proteinaceous component of the extracellular matrix (ECM). The ECM is a critical medium for cell-cell interactions and can also directly signal cells through cell surface ECM receptors, such as integrins. In addition, many growth factors and signaling molecules are stored in the ECM. Thus, ECM remodeling and/or degradation by MMPs are expected to affect cell fate and behavior during many developmental and pathological processes. Numerous studies have shown that the expression of MMP mRNAs and proteins associates tightly with diverse developmental and pathological processes, such as tumor metastasis and mammary gland involution. In vivo evidence to support the roles of MMPs in these processes has been much harder to get. Here, we will review some of our studies on MMP11, or stromelysin-3, during the thyroid hormone-dependent amphibian metamorphosis, a process that resembles the so-called postembryonic development in mammals (from a few months before to several months after birth in humans when organ growth and maturation take place). Our investigations demonstrate that stromelysin-3 controls apoptosis in different tissues via at least two distinct mechanisms. PMID- 20301222 TI - Therapeutic potential of the immunomodulatory activities of adult mesenchymal stem cells. AB - Adult mesenchymal stem cells (MSCs) include a select population of resident cells within adult tissues, which retain the ability to differentiate along several tissue-specific lineages under defined media conditions and have finite expansion potential in vitro. These adult progenitor populations have been identified in various tissues, but it remains unclear exactly what role both transplanted and native MSCs play in processes of disease and regeneration. Interestingly, increasing evidence reveals a unique antiinflammatory immunomodulatory phenotype shared among this population, lending support to the idea that MSCs play a central role in early tissue remodeling responses where a controlled inflammatory response is required. However, additional evidence suggests that MSCs may not retain infinite immune privilege and that the context with which these cells are introduced in vivo may influence their immune phenotype. Therefore, understanding this dynamic microenvironment in which MSCs participate in complex feedback loops acting upon and being influenced by a plethora of secreted cytokines, extracellular matrix molecules, and fragments will be critical to elucidating the role of MSCs in the intertwined processes of immunomodulation and tissue repair. PMID- 20301223 TI - Laying the groundwork for growth: Cell-cell and cell-ECM interactions in cardiovascular development. AB - Cardiac development is reliant upon the spatial and temporal regulation of both genetic and chemical signals. Central to the communication of these signals are direct interactions between cells and their surrounding environment. The extracellular matrix (ECM) plays an integral role in cell communication and tissue growth throughout development by providing both structural support and chemical signaling factors. The present review discusses elements of cell-cell and cell-ECM interactions involved in cardiogenesis, and how disruption of these interactions can result in numerous heart defects. Examining the relationships between cells and their immediate environment has implications for novel and existing therapeutic strategies to combating congenital disorders. PMID- 20301224 TI - Molecular characterization of two novel deltamethrin-inducible P450 genes from Liposcelis bostrychophila Badonnel (Psocoptera: Liposcelididae). AB - Two novel P450 genes, CYP6CE1 and CYP6CE2 (GenBank accession number: EF421245 and EF421246), were cloned and characterized from psocid, Liposcelis bostrychophila. CYP6CE1 and CYP6CE2 contain open reading frames of 1,581 and 1,563 nucleotides that encode 527 and 521 amino acid residues, respectively. The putative proteins of CYP6CE1 and CYP6CE2 show predicted molecular weights of 60.76 and 59.83 kDa with a theoretical pI of 8.58 and 8.78, respectively. CYP6CE1 and CYP6CE2 share 74% identity with each other, and the deduced proteins are typical microsomal P450s sharing signature sequences with other insect CYP6 P450s. Both CYP6CE1 and CYP6CE2 share the closest identities with Hodotermopsis sjoestedti CYP6AM1 at 48% among the published sequences. Phylogenetic analysis showed a closer relationship of CYP6CE1 and CYP6CE2 with CYP6 members of other insects than with those from other families. Quantitative real-time RT-PCR showed that both CYP6CE1 and CYP6CE2 are expressed at all developmental stages tested. Interestingly, CYP6CE2 transcripts decreased from the highest in 1st nymph to the lowest in adults, which seemed to suggest developmental regulation. However, neither CYP6CE1 nor CYP6CE2 were stage specific. The CYP6CE1 and CYP6CE2 transcripts in adults increased significantly after deltamethrin exposure. Recombinant protein expression studies are needed to determine the real functions of these proteins. PMID- 20301225 TI - The venlafaxine "heart revenge:" a short report. AB - A 40-year-old white woman with a history of venlafaxine abuse was admitted to our emergency department within 3 days after attempting suicide. On admission, blood pressure was 140/85 mm Hg with 70 beats per minute. The resting 12-lead ECG showed a significant ST-segment elevation in the anterolateral leads consistent with acute anterolateral myocardial infarction (anterolateral AMI). Noninvasive monitoring of blood oxygen saturation showed 97% while she was breathing room air. Laboratory findings showed the increase of troponin I up to 16 microg/L (normal range, 0-0.05 microg/L) and creatine kinase MB subunit levels up to 166 U/L (normal range, 0-25 U/L). An emergency coronary angiogram was normal. Venlafaxine is generally prescribed for the treatment of major depression, as well as, generalized and social anxiety. This is the first time in the literature that we describe an association between myocardial infarction and an overdose with venlafaxine. PMID- 20301226 TI - A large family from Argentina with prekallikrein deficiency due to a compound heterozygosis (T insertion in intron 7 and Asp558Glu in exon 15): prekallikrein Cordoba. PMID- 20301227 TI - A literature review regarding the management of varicella-zoster virus. AB - Chickenpox and shingles (varicella-zoster virus [VZV]) pose a threat to individuals who are immunosuppressed and/or have rheumatoid arthritis or another inflammatory musculoskeletal condition. In this paper we present a literature review of the condition, management and prevention. PMID- 20301228 TI - Teaching medical students about chronic disease: patient-led teaching in rheumatoid arthritis. AB - OBJECTIVES: To evaluate the effectiveness of patient-led teaching compared with doctor-led teaching, regarding the impact of chronic disease (rheumatoid arthritis [RA]). METHODS: A set of learning objectives regarding the impact of RA on patient and family was designed. Students (n = 42) attached to the academy for their musculoskeletal diseases module were randomized to teaching either by a doctor or a patient. Outcome was assessed using a knowledge test, feedback forms and qualitative written interview. RESULTS: In the knowledge test, the groups performed equally. The patient-taught group scored 24.5 +/- 3.5 (max 35); the doctor-taught group scored 24.6 +/- 4.1 (p > 0.05; NS). Feedback was completed by 40/42 students. Mean scores for the overall grading of teaching (1-5, where 1 = worst, 5 = best) were: patient teaching 4.36 (95% confidence interval [CI] 4.11, 4.61); doctor teaching 3.69 (95% CI 3.52, 3.92).The difference between the average scores was 0.42 (p = 0.005). Qualitative feedback showed recurring themes that students appreciated the personal nature of the patient's teaching, enabling them to understand the impact of the disease on patients and their families. The doctors' teaching was also appreciated, particularly the interactive style and opportunity to participate in role play. CONCLUSIONS: We have demonstrated that our patient was at least as good as a doctor at teaching about the impact of chronic disease on patients. Furthermore, this experience is valued by students who appreciate the personal insight that a patient can offer. PMID- 20301793 TI - [EPI-CLIN 3rd French-speaking Conference of Clinical Epidemiology, Fes, Morocco, 7-8 May 2009. Abstracts]. PMID- 20301229 TI - A non-functioning vitamin D receptor predisposes to leukaemoid reactions in mice. AB - The vitamin D hormone 1,25-dihydroxyvitamin D(3) [1,25(OH)(2) D(3) ], the biologically active form of vitamin D, is not only essential for mineral metabolism but may have important functions beyond calcium homoeostasis. By gene targeting, we have recently generated mice expressing a functionally inactive mutant vitamin D receptor (VDR). After a change in environmental conditions from specific pathogen free (SPF) conditions to a modified barrier system, a high percentage of aged mutant, but not wild-type, mice developed a haematological disorder characterized by splenomegaly, granulocytosis, thrombocytosis and dysplastic changes with displacement of erythropoiesis in bone marrow during the following months. All cases were associated with very high serum levels of the acute phase reaction protein serum amyloid A (SAA). Serological testing of affected mice revealed antibodies against murine hepatitis virus (MHV). However, electron microscopy of spleen and bone marrow cells did not reveal virus particles, and clinical signs of infectious diseases were absent. We hypothesize that a non-functioning VDR is associated with a latent defect in the regulation of myeloid cell differentiation and proliferation. Under the conditions of environmental stress, this latent defect may predispose to a deregulation of myelopoiesis in the form of a leukaemoid reaction accompanied by dysplastic changes. Thus, 1,25(OH)(2) D(3) may be an important inhibitory factor in the onset and progression of myeloproliferative and myelodysplastic diseases. PMID- 20301794 TI - The explant can safely remove cemented acetabular components. PMID- 20301795 TI - Niacin compared with ezetimibe. PMID- 20301796 TI - Niacin compared with ezetimibe. PMID- 20301797 TI - Niacin compared with ezetimibe. PMID- 20301798 TI - Platelet inhibition with cangrelor. PMID- 20301799 TI - Papillary fibroelastoma of an anomalous mitral valve chorda. AB - Cardiac papillary fibroelastoma (CPF) is a rare primary cardiac tumour. This tumour constitutes about 10-15% of all primary cardiac tumours. We report here a case of CPF of an anomalous mitral valve chorda. PMID- 20301800 TI - Dabigatran versus warfarin for venous thromboembolism. PMID- 20301801 TI - Continuing medical education--limiting industry's influence. PMID- 20301802 TI - Continuing medical education--limiting industry's influence. PMID- 20301803 TI - Knee arthroscopy: viewing the posterior horn of the medial meniscus. PMID- 20301804 TI - An alternative use of Foley catheters in Ilizarov external fixation. PMID- 20301805 TI - Pre-contouring plates using synthetic bone models as a template to aid minimal access fracture fixation. PMID- 20301806 TI - A simple technique for in situ renal artery perfusion during abdominal aortic aneurysm repair. PMID- 20301807 TI - Suction retractor: a useful aid for deep plane dissections. PMID- 20301808 TI - 'Boot' as a 'collar' - a simple solution to shunt slippage. PMID- 20301809 TI - The use of Goldfinger(TM)(Ethicon Endo Surgery) to facilitate laparoscopic distal pancreatectomy. PMID- 20301810 TI - Use of a K-wire as an aid to ensuring an accurate neck cut during hip hemi arthroplasty. PMID- 20301811 TI - Dual-eligibles: a better way. PMID- 20301812 TI - Application of SYPRO Ruby- and Flamingo-stained polyacrylamide gels to Western blot analysis. AB - Western blots are widely used for analysis of the expression levels of specific proteins. Blotting is conducted after sodium dodecyl sulfate or native polyacrylamide gel electrophoresis without staining the gel. However, when it is necessary to analyze the gel, duplicate polyacrylamide gels (one of which is stained) usually must be prepared, leading to the consumption of precious sample. Thus, we have developed a convenient and efficient Western blot method using a stained gel. This simple modification should be beneficial for the analysis of samples that are limited in quantity and/or samples for which the stained gel serves as the loading control. PMID- 20301813 TI - Environmental effects of ozone depletion and its interactions with climate change: progress report, 2009. AB - The parties to the Montreal Protocol are informed by three panels of experts. One of these is the Environmental Effects Assessment Panel (EEAP), which deals with UV radiation and its effects on human health, animals, plants, biogeochemistry, air quality and materials. Since 2000, the analyses and interpretation of these effects have included interactions between UV radiation and global climate change. When considering the effects of climate change, it has become clear that processes resulting in changes in stratospheric ozone are more complex than believed previously. As a result of this, human health and environmental problems will likely be longer-lasting and more regionally variable. Like the other panels, the EEAP produces a detailed report every four years; the most recent was that for 2006 (Photochem. Photobiol. Sci., 2007, 6, 201-332). In the years in between, the EEAP produces a less detailed and shorter progress report, as is the case for this present one for 2009. A full quadrennial report will follow for 2010. PMID- 20301814 TI - Winds of change: growing demands for transparency in the relationship between doctors and the pharmaceutical industry. PMID- 20301815 TI - Culture care meanings, beliefs, and practices in Rural Dominican Republic. AB - PURPOSE: This ethnonursing study explored the meanings, beliefs, and practices of care for rural Dominicans in the Dominican Republic. DESIGN: Leininger's culture care diversity and universality theory, ethnonursing, and four-phase analysis method guided the study. Interviews were conducted with 19 general and 10 key informants. FINDINGS: Analysis of interviews revealed three main themes: (a) family presence is essential for meaningful care experiences and care practices, (b) respect and attention are central to the meaning of care and care practices, and (c) rural Dominicans value and use both generic (folk) and professional care practices. DISCUSSION AND CONCLUSION: Implications and recommendations for nursing practice, education, and research are described. PMID- 20301816 TI - Providing care for migrant farm worker families in their unique sociocultural context and environment. AB - This article highlights the Farm Worker Family Health Program's (FWFHP) strategies for providing care to migrant farm workers residing within a unique social and cultural context. The care provided by health professions students from a variety of disciplines extends and augments the work of the local migrant farm worker clinic that is pushed beyond capacity during peak growing and harvest times. Nursing's social responsibility to care for underserved populations is a guiding principle of the FWFHP and shapes how the work is translated into action. The FWFHP is a community-academic partnership that began in the rural southeastern United States in 1993. Challenges facing migrant farm worker families include access to health care, language, health literacy, housing and sanitation, family and community integrity, and workplace safety. The nursing practice strategies used to address these health challenges may be adapted to strengthen health programs serving other populations who live in poverty or reside in low-resource settings. PMID- 20301817 TI - Case studies of Hispanic caregivers of persons with dementia: reconciliation of self. AB - An interpretive phenomenology perspective is used to explore the lived experience of two Hispanic caregivers and the phenomenon of mastery. The analysis showed how theses caregivers derive meaning of their experience through a process of reconciliation of self between the roles of parental caretaker, respectful daughter, and caregiver. This reconciliation of self is a form of mastery, and the process of reconciliation is grounded in cultural values of intergenerational reciprocity and familism. Nurses have the unique opportunity to support a caregiver in his or her interaction with the person with dementia. The implications for practice include the need for nurses to acknowledge, validate, and support caregiver's experience of reconciling self as a form of health promotion. PMID- 20301818 TI - Incorporating cultural competence content into graduate nursing curricula through community-university collaboration. AB - Health professionals are reorienting workforce education to better prepare students for working with increasingly diverse populations. The authors describe a community-based curriculum deliberation process in which community leaders and health workers deliberated with faculty and students to make recommendations about a graduate nursing curriculum. There were five areas of competencies recommended for graduate nursing to improve care of diverse populations: self awareness, basic knowledge of culture and identity, attitudes that promote cross cultural communication, cross-cultural clinical skills, and advocacy skills. The school now is in the process of phasing in recommendations gained from the deliberation. PMID- 20301819 TI - Ultrasound-guided continuous femoral nerve block for analgesia after total knee arthroplasty: catheter perpendicular to the nerve versus catheter parallel to the nerve. AB - BACKGROUND AND OBJECTIVES: This study tested the hypothesis that, in continuous femoral nerve block (CFNB) under ultrasound guidance, placing a catheter perpendicular to the nerve can shorten the time of catheter insertion while providing a similar quality of analgesia compared with placing a catheter parallel to the nerve. METHODS: Fifty patients undergoing total knee arthroplasty were randomly assigned to receive ultrasound-guided CFNB either with the catheter parallel to the nerve technique (parallel group, n = 25) or with the catheter perpendicular to the nerve technique (perpendicular group, n = 25). Patient controlled morphine analgesia pumps were available to all the patients after surgery. The time of catheter insertion, failure rates, pain scores, morphine consumption, nausea and vomiting, and maximal degree of knee flexion were recorded. RESULTS: The time of catheter insertion was shorter in the perpendicular group than in the parallel group (12 +/- 3 versus 22 +/- 6 mins, P < 0.01). Failed catheter insertion occurred in 3 (12%) of 25 patients in the parallel group and in none of 25 patients in the perpendicular group (P = 0.2347). There were no significant differences in pain scores, opioid consumption, incidence of nausea and vomiting, and maximal degree of knee flexion between the 2 groups. CONCLUSIONS: In CFNB under ultrasound guidance, using the catheter perpendicular to the nerve technique can shorten the time of catheter insertion while providing a similar quality of analgesia after total knee arthroplasty as compared with the catheter parallel to the nerve technique. PMID- 20301820 TI - Safety of high volume lipid emulsion infusion: a first approximation of LD50 in rats. AB - BACKGROUND: Lipid infusion reverses systemic local anesthetic toxicity. The acceptable upper limit for lipid administration is unknown and has direct bearing on clinical management. We hypothesize that high volumes of lipid could have undesirable effects and sought to identify the dose required to kill 50% of the animals (LD(50)) of large volume lipid administration. METHODS: Intravenous lines and electrocardiogram electrodes were placed in anesthetized, male Sprague-Dawley rats. Twenty percent lipid emulsion (20, 40, 60, or 80 mL/kg) or saline (60 or 80 mL/kg), were administered over 30 mins; lipid dosing was assigned by the Dixon "up-and-down" method. Rats were recovered and observed for 48 hrs then euthanized for histologic analysis of major organs. Three additional rats were administered 60 mL/kg lipid emulsion and euthanized at 1, 4, and 24 hrs to identify progression of organ damage. RESULTS: The maximum likelihood estimate for LD(50) was 67.72 (SE, 10.69) mL/kg. Triglycerides were elevated immediately after infusion but returned to baseline by 48 hrs when laboratory abnormalities included elevated amylase, aspartate aminotransferase, and serum urea nitrogen for all lipid doses. Histologic diagnosis of myocardium, brain, pancreas, and kidneys was normal at all doses. Microscopic abnormalities in lung and liver were observed at 60 and 80 mL/kg; histopathology in the lung and liver was worse at 1 hr than at 4 and 24 hrs. CONCLUSIONS: The LD(50) of rapid, high volume lipid infusion is an order of magnitude greater than doses typically used for lipid rescue in humans and supports the safety of lipid infusion at currently recommended doses for toxin-induced cardiac arrest. Lung and liver histopathology was observed at the highest infused volumes. PMID- 20301821 TI - Spinal Anesthesia and Intrathecal Clonidine Decrease the Hypnotic Requirement of Propofol. AB - BACKGROUND AND OBJECTIVES: Spinal anesthesia and intrathecal clonidine are known to have hypnotic effects. We investigated the effect of spinal anesthesia and intrathecal clonidine on the requirement of propofol for sedation. METHODS: Sixty adult patients scheduled for stripping and ligation of varicose veins under local or spinal anesthesia were enrolled in this study. Group 1 included patients given local anesthesia, group 2 included patients given spinal anesthesia, and group 3 included patients given spinal anesthesia with 75 microg of clonidine. Target controlled infusion of propofol was started to achieve a target concentration of 1 and 1.5 microg/mL, and the mean bispectral index (BIS) for 1 min was checked after an effect site concentration (Ce) of 1 and 1.5 microg/mL propofol was reached. In addition, the Ce of propofol was documented when the mean BIS for 1 min reached 80 and 70 for the 3 groups, respectively, during the observation period. RESULTS: The BIS at 1 microg/mL propofol Ce was 87 (group 1), 80 (group 2), and 69 (group 3). The BIS at 1.5 microg/mL propofol Ce was 76, 64, and 51, respectively. The Ce of propofol when the BIS first reached 80 was 1.4, 1.1, and 0.7 microg/mL, respectively. The Ce of propofol when the BIS first reached 70 was 1.7, 1.4, and 0.9 microg/mL, respectively. CONCLUSIONS: Spinal anesthesia and intrathecal clonidine might reduce the requirement of propofol for sedation. Our study showed target concentrations of propofol for sedation of 1.4 to 1.7 using local anesthesia only, 1.1 to 1.4 using spinal anesthesia with bupivacaine, and 0.7 to 0.9 microg/mL using spinal anesthesia with bupivacaine and 75 microg of clonidine PMID- 20301822 TI - Pulsed radiofrequency for the treatment of occipital neuralgia: a prospective study with 6 months of follow-up. AB - BACKGROUND AND OBJECTIVES: Occipital neuralgia is a paroxysmal nonthrobbing, stabbing pain in the area of the greater or lesser occipital nerve caused by irritation of these nerves. Although several therapies have been reported, no criterion standard has emerged. This study reports on the results of a prospective trial with 6 months of follow-up in which pulsed radiofrequency treatment of the greater and/or lesser occipital nerve was used to treat this neuralgia. METHODS: Patients presenting with clinical findings suggestive of occipital neuralgia and a positive test block of the occipital nerves with 2 mL of local anesthetic underwent a pulsed radiofrequency procedure of the culprit nerves. Mean scores for pain, quality of life, and medication intake were measured 1, 2, and 6 months after the procedure. Pain was measured by the visual analog and Likert scales, quality of life was measured by a modified brief pain questionnaire, and medication intake was measured by a Medication Quantification Scale. RESULTS: During a 29-month period, 19 patients were included in the study. Mean visual analog scale and median Medication Quantification Scale scores declined by 3.6 units (P = 0.002) and 8 units (P = 0.006), respectively, during 6 months. Approximately 52.6% of patients reported a score of 6 (pain improved substantially) or higher on the Likert scale after 6 months. No complications were reported. CONCLUSIONS: Pulsed radiofrequency treatment of the greater and/or lesser occipital nerve is a promising treatment of occipital neuralgia. This study warrants further placebo-controlled trials. PMID- 20301823 TI - Models and mechanisms of local anesthetic cardiac toxicity: a review. AB - Cardiovascular collapse, even death, may occur after intoxication with bupivacaine or related amide local anesthetic agents. The problem has been studied in myriad laboratories for more than 20 years. Nevertheless, there is consensus neither regarding which animal model best mimics this clinical catastrophe nor as to which ion channel, enzyme, or other local anesthetic binding site represents the point of initiation for the process. This review aimed to define the various credible mechanisms that have been proposed to explain cardiovascular collapse and death after administration of local anesthetics, particularly after bupivacaine and related agents. PMID- 20301824 TI - Clinical presentation of local anesthetic systemic toxicity: a review of published cases, 1979 to 2009. AB - The classic description of local anesthetic systemic toxicity (LAST) generally described in textbooks includes a series of progressively worsening neurologic symptoms and signs occurring shortly after the injection of local anesthetic and paralleling progressive increases in blood local anesthetic concentration, culminating in seizures and coma. In extreme cases, signs of hemodynamic instability follow and can lead to cardiovascular collapse. To characterize the clinical spectrum of LAST and compare it to the classic picture described above, we reviewed published reports of LAST during a 30-year period from 1979 to 2009. Ninety-three cases were identified and analyzed with respect to onset of toxicity and the spectrum of signs and symptoms. Sixty percent of cases followed the classic pattern of presentation. However, in the remainder of cases, symptoms were substantially delayed after the injection of local anesthetic, or involved only signs of cardiovascular compromise, with no evidence of central nervous system toxicity. Although information gained from retrospective case review cannot establish incidence, outcomes, or comparative efficacies of treatment, it can improve awareness of the clinical spectrum of LAST and, theoretically, the diagnosis and treatment of affected patients. The analytic limitations of our method make a strong case for developing a prospective, global registry of LAST as a robust alternative for educating practitioners and optimizing management of LAST. PMID- 20301825 TI - Wound spread of radiolabeled saline with multi- versus few-hole catheters. AB - BACKGROUND AND OBJECTIVES: Continuous wound infusion of local anesthetics is effective in postoperative pain management and may be useful in major joint arthroplasty, but the optimal technique for postoperative administration of local anesthetics in the wound awaits trials evaluating the optimal type of catheter (single-, few-, or multiholed catheters). METHODS: Sixteen patients undergoing total hip arthroplasty were randomized to intraoperative subfascial placement of a triple-orifice epidural catheter or a 15-cm multiholed catheter. Twenty milliliters of technetium Tc 99m diethylenetriaminepentaacetic acid-labeled saline was injected postoperatively and wound spread for 10 mins was recorded with a double-head gamma camera. RESULTS: Mean (SD) wound spread (cm(2)) was the same with administration through a multiholed catheter versus the epidural catheter in both anterior (89 [15] versus 82 [20], P = 0.4) and lateral (68 [19] versus 60 [11], P = 0.3) projections. CONCLUSIONS: Wound spread of a bolus injection through 15-cm multiholed catheters versus triple-orifice epidural catheters is similar with subfascial catheter placement in total hip arthroplasty. Procedure-specific trials are required to evaluate the analgesic efficacy of postoperative administration of local anesthetic in the wound with different types of catheter before general recommendations can be made. PMID- 20301826 TI - Sonographic identification of needle tip by specialists and novices: a blinded comparison of 5 regional block needles in fresh human cadavers. AB - BACKGROUND AND OBJECTIVES: Needle visibility using ultrasound remains problematic at steep insertion angles. Despite modified techniques, steep approaches are still needed, particularly in the obese, neuraxial anesthesia or pain blocks around the spine. We describe a novel technique for objective assessment of needle-tip identification and present data on a new needle. METHODS: Five needles were compared for accuracy of tip position identification. Pajunk facet-tipped, Tuohy-tipped, Polymedic Ultrasound, Hakko EchoStim, and a new intermittently textured needle (T). Static ultrasound images were obtained of the needles in first-thaw, unembalmed cadavers at shallow, moderate and steep angles. Actual tip position was defined. Images were presented in blinded, random order to 10 experienced and 10 novice anesthetists who estimated tip position. Distance between true tip position and estimated position was measured ("tip error"). Secondary objectives included subjective measures of visibility and differences between needles at shallower insertion angles and between novice and expert observers. RESULTS: At steep angles, study needles varied significantly with regard to tip error (P < 0.0001). Needle T scored highest for confidence and subjective visibility at moderate and steep angles. There was no significant difference between novice and experienced anesthetists for tip error or visibility. Experts were more confident in their estimates. CONCLUSIONS: Needle T demonstrated good properties even at steep insertion angles. Tip location was accurate, and observers rated it highly visible. Ability to identify needle-tip position can be objectively assessed. PMID- 20301827 TI - In-plane ultrasound-guided thoracic paravertebral block: a preliminary report of 36 cases with radiologic confirmation of catheter position. AB - BACKGROUND AND OBJECTIVES: Thoracic paravertebral block (TPVB) can be used for unilateral surgical procedures. Modifications of the classic approach have been proposed to minimize the risk of pleural puncture. In this study, we evaluated the feasibility and success rate of a transverse in-plane ultrasound (US)-guided TPVB with radiologic confirmation of catheter position. METHODS: A total of 36 patients scheduled for unilateral surgery with a TPVB catheter were included in this prospective study. Ultrasonographically, the transverse process of the thoracic vertebra and rib were identified at the appropriate thoracic level. The transducer was moved cranially until an intercostal US view was obtained, indicated by visualization of the parietal pleura. An in-plane needle insertion approach from lateral to medial was used, and a total of 20 mL ropivacaine 0.75% was injected through the needle and a subsequently threaded catheter, while the spread of local anesthetic was observed. Sensory spread of the block was evaluated by loss of cold sensation in the dermatomes. Catheter position was radiologically evaluated with radiopaque dye. RESULTS: Block success rate was 100%. In all patients, correct radiologic thoracic paravertebral catheter position was confirmed; 1 patient also showed additional epidural spread. The median number of total dermatomal segments with loss of cold sensation was 6. No pneumothorax or contralateral loss of cold sensation occurred. CONCLUSION: An in plane transverse US-guided TPVB using the described technique is feasible and has a high success rate. In all patients, correct catheter position in the thoracic paravertebral space was radiologically confirmed. PMID- 20301828 TI - Ultrasound does not improve the success rate of a deep peroneal nerve block at the ankle. AB - BACKGROUND: The deep peroneal nerve is 1 of 5 nerves anesthetized when performing an ankle block. Multiple techniques of blocking the deep peroneal nerve have been described, but little evidence exists to delineate the efficacy of any one technique. We hypothesized that ultrasound would increase both the success rate and the quality of a deep peroneal nerve block at the ankle. METHODS: Eighteen healthy volunteers participated in this randomized, controlled, prospective study. Each subject was randomly assigned to receive an ultrasound-guided deep peroneal nerve block of either the right or the left ankle. The deep peroneal nerve on the opposite side was blocked using a conventional landmark technique. Subjects were blinded to the technique used. All blocks were preformed with 5 mL of 3% 2-chloroprocaine. We evaluated both sensory and motor blocks at 10-min intervals for 60 mins. RESULTS: Blocks were maximal in both groups at 20 to 30 mins. There was a statistically significant difference in temperature sensation and motor function at 10 mins favoring the ultrasound group. There was no statistical difference in motor function, temperature, or pinprick sensation between 20 and 60 mins. CONCLUSIONS: The use of ultrasound seems to improve the onset of deep peroneal nerve block at the ankle but does not improve the overall quality of the block. PMID- 20301829 TI - Special anniversary volume - issue 6: replacement - focus on the testing of chemicals and products. Preface. PMID- 20301830 TI - Mail-order versus local pharmacies on adherence: study methods make for unfair comparison. PMID- 20301831 TI - Case law update: a review of recent rulings of interest to risk managers. Harrison v. Binnion, No. 34731(Idaho, July 7, 2009). PMID- 20301832 TI - Case law update: a review of recent rulings of interest to risk managers. Vazquez Rivera v. Hospital Episcopal San Lucas, Civil No. 08-2223 (JP) (D.P.R. May 25, 2009). PMID- 20301833 TI - Case law update: a review of recent rulings of interest to risk managers. Jones v HealthSouth Treasure Valley Hospital, 206 P.3d 473 (Idaho 2009). PMID- 20301834 TI - [Q & A. An emergency case admitted with hematemesis followed by exacerbation of abdominal pain]. PMID- 20301835 TI - [New aspects of tumor pathobiology]. AB - Several biological principles such as epigenetic changes, RNA interference, epithelial-mesenchymal transition, and cancer stem cell formation have been recently connected to the pathobiology of tumors. All these phenomena have, along with genetic changes, a significant impact on the neoplastic transformation and/or tumor progression. Authors report a review of the above mentioned "nongenetic" processes and their effect on the neoplastic transformation, and the appearance, behavior, prognosis, and therapy of tumors. Future diagnostic and therapeutic perspectives are also discussed. PMID- 20301836 TI - [What is your diagnosis? Composite pheochromocytoma with a ganglioneuroma component]. PMID- 20301837 TI - [Detection of regulatory protein p16/INK4A in the dysplastic cervical squamous cell epithelium is a diagnostic tool for carcinoma prevention]. AB - Parallel sections from 423 randomly selected blocks representing biopsies of 178 women with the diagnosis of cervical dysplasia and/or erosion were stained for p16 polypeptide. The p16/INK4A (inhibitory kinase 4) protein is a cellular division regulator, expression of which increases in the presence of oncoprotein E7, encoded by human papillomavirus (HPV). Expression of p16 protein was seen in the nuclei and cytoplasm of dysplastic squamous epithelium cells as well as in carcinoma cells. In 16.6% of erosion cases, the p16 antigen was present in the basal and suprabasal layer of the surrounding squamous epithelium revealing features of CIN I/LSIL. In CIN I/LSIL as classified by HE staining, the p16 antigen was found in 65 out of 80 (81%) cases. The p16 protein was typically seen in dysplastic basal and suprabasal cells encompassing a confluent layer in the lowest third segment of stratified epithelium. In CIN II and CIN III grouped as HSIL, the positive rate of p16 antigen presence was 95% (in 45 cases out of 47) and/or 100% (in each of 27 cases), respectively. The typical sign of p16 antigen distribution in HSIL was its staining over two thirds and/or throughout the whole dysplastic epithelium. Extensive staining for p16 antigen was registered within nuclei as well as cytoplasm of neoplastic cells in all 6 cervical squamous cell carcinomas, which were examined in many sections when being used as positive controls. Based on our experience, we consider the p16 antigen staining a helpful tool indicating dysplastic cells and estimating their extent. PMID- 20301838 TI - Mammaglobin immunostaining in the differential diagnosis between cutaneous apocrine carcinoma and cutaneous metastasis from breast carcinoma. AB - The differential diagnosis between cutaneous apocrine carcinoma (CAC) and cutaneous metastases from breast carcinoma is commonly difficult. Many times, clinical information is crucial in the final diagnosis, because help that can be obtained from immunohistochemistry is usually limited concerning this subject. We used the antibody mammaglobin in order to study 10 cases of cutaneous metastasis of ductal breast carcinoma, and 2 cases of CAC. One of the CAC cases showed only scattered positive cells, while the other did not show any positivity. Four cases of metastatic breast carcinoma also showed scattered positive cells. In other five metastatic cases, positive cells were abundant, representing up to 60% of the tumoral cells. One case of metastatic breast carcinoma did not show any expression of mammaglobin at all. Although, more cases of CAC should probably be studied in the future before any categorical conclusion can be obtained, our results seem to indicate that a pattern of immunostaining with expression of mammaglobin in many cells would favor a metastatic origin of the tumor. PMID- 20301840 TI - [Congenital granular cell epulis: a case report]. AB - Congenital granular cell epulis is a rare benign lesion occuring exclusively in newborns as a solitary or multiple swelling of alveolar mucosa of either maxilla or mandible. A case of a female newborn who presented with multiple swellings of both maxillary and mandibular alveolar mucosa measuring up to 10 mm is presented. On 24th postnatal day, the lesions were under general anesthesia excised and sent for microscopic examination, which revealed congenital granular cell epulis. Immunohistochemically, granular cells showed expression of both vimentin and PGP 9.5, whereas the proof of S100 protein and inhibin was negative. The postoperative course was uneventful and follow-up for 8 months showed no local recurrence. PMID- 20301839 TI - [Unusual clinical presentation of hepatic yolk sac tumour in periappendical region. A case report and review of the literature]. AB - Primary hepatic yolk sac tumour (YST) is a very rare neoplasm. The authors present a case of a 20-year-old woman with fever and pain in the epigastrium, clinically resembling acute appendicitis along with high levels of serum alpha fetoprotein. From laparoscopic appendectomy there was bioptically verified a diagnosis of YST. Consequently, there was discovered a tumor in the liver and the patient underwent right hemihepatectomy, hemicolectomy and ovariectomy, from which the YST was disclosed in the liver and in the coecum with spread into regional lymph nodes. While the gonadal, mediastinal and central nervous system origin of the YST was excluded, the diagnosis of the primary hepatic YST could have been established. The exact etiology of primary hepatic YST is still unclear. It has been suggested that these YSTs might originate from the germ cells that escaped during migration course from the yolk sac to the genital ridge during embryogenesis with subsequent malignant transformation or from persistent pluripotent embryonic cells in the liver, which escaped from the influence of differentiation during embryogenesis. This tumour is aggressive with ability to spread into distant sites, where it can lead to the first clinical presentation. PMID- 20301841 TI - Necker in Scotch perspective. PMID- 20301842 TI - Measuring the Breathing Light Illusion by means of induced simultaneous contrast. AB - By blurring the margins of a surface, both its brightness and the perceived contrast against a superimposed figure with sharp boundaries increase. Also, if one approaches a blurred white spot on a grey background, this spot will appear wider and brighter: this phenomenon is known as the Breathing Light Illusion (BLI) (Gori and Stubbs, 2006 Perception 35 1573-1577). We studied the increment of the achromatic contrast of a grey sharp-boundary disk when it was superimposed on the BLI. This augmentation of the perceived contrast in the dynamic presentation of the BLI was significantly stronger than the effect that Agostini and Galmonte (2002a Psychonomic Bulletin and Review 9 264-269) obtained in static presentation. Our study leads to an indirect quantification of the BLI. Two control experiments showed that the increment of the achromatic contrast depends on the blurred spot and is independent of the dynamic increment in angular size. These results argue for a causal relationship between the increase in brightness due to the BLI and the darkening of the superimposed disk. PMID- 20301843 TI - Spatial distortions induced by dotted patterns. AB - Prolonged steady fixation of parallel, radial, or concentric lines positioned close to each other generates phenomena of illusory oscillation, waving, and shimmering. Purkinje reported a first observation of these phenomena almost two centuries ago (review by Wade, 1977 Perception 6 407-433). Here we show that illusory waving and oscillation phenomena arise at first glance when dotted lines are either interposed between continuous lines, or positioned very close to straight edges. Phenomenological and individual observations indicate that dotted and linear patterns are independent sources of different illusory effects: the former of waving, the latter of shimmering/scintillating. The two effects enhance each other when dotted and continuous lines are alternated. Possible accounts of the phenomena are discussed. Waving is likely to originate from the perceived alteration of dot spacing, which in turn gives rise to depth cues and the consequent illusory deviation in depth. Shimmering and scintillating are attributed to imperfect binocular fusion, which can cause phenomena of brightness induction. A theory of the combination of the two illusory effects is put forward. PMID- 20301844 TI - Sensitivity to reflection and translation is modulated by objectness. AB - The salience of a transformation between a pair of contours depends on the type of transformation (eg a reflection or a translation) and also on figure-ground organisation. Reflection is most salient when both contours belong to the same surface, and translation is most salient when they do not connect a surface. These findings are based on reaction time (RT). Here I replicate and extend them by measuring both RT and sensitivity. The figure-ground relations were changed unambiguously by using stereograms. I compared reflection and translation when they were present within a surface or across surfaces (experiment 1), and within an object or a hole (experiments 2-4). Holes are interesting because they are not objects, but their presence does not increase the number of total objects in the scene. The within-surface advantage for reflection was present in all experiments. There was a between-surface advantage for translation in experiment 1 but there was no hole advantage for translation in experiments 2-4. Thus the effect of context, ie objectness, on detection of regularity is a robust and general phenomenon present in every experiment, but the type of interaction differs for reflection and translation. PMID- 20301845 TI - The effect of cognitive distraction on saccadic latency. AB - Saccadic initiation is increasingly being studied as a surrogate for more general neural mechanisms of decision-making. Visual 'decision-making' is thought to be controlled by higher cortical functions. Lower areas such as the superior colliculus are thought to be involved with more primitive optomotor reflexes that can generate short-latency saccades. It is now well established that imposition of fronto-executive load on subjects performing a saccadic task which, in particular, involves suppression of saccades (the no-go saccadic task), increases the number of errors made. It is theorised that a weakening of cortical control of the superior colliculus is responsible for the increase in error rate. One way to test this theory is to measure the latency of incorrect saccades made in a no go saccadic task in relation to error rate under different conditions of fronto executive load. A high error rate combined with an increased number of short latency saccades in the range of express or early saccades would indicate that subjects have an inability to inhibit these short-latency more reflexive saccades, which seem to originate in the superior colliculus. Hence the normal cortical control of the superior colliculus is weakened. We used a saccadic go/no go task under fronto-executive load and found that the proportion of short latency saccades increased with audio-verbal interference, in conjunction with an increase in error rate. These findings provide strong empirical evidence to support the theory that maintenance of cortical functions is key to the control of saccadic responses. Under conditions of fronto-executive loading such cortical control is weakened, leaving subjects with a reduced ability to inhibit short latency more reflexive saccades. PMID- 20301846 TI - Deciphering faces: quantifiable visual cues to weight. AB - Body weight plays a crucial role in mate choice, as weight is related to both attractiveness and health. People are quite accurate at judging weight in faces, but the cues used to make these judgments have not been defined. This study consisted of two parts. First, we wanted to identify quantifiable facial cues that are related to body weight, as defined by body mass index (BMI). Second, we wanted to test whether people use these cues to judge weight. In study 1, we recruited two groups of Caucasian and two groups of African participants, determined their BMI and measured their 2-D facial images for: width-to-height ratio, perimeter-to-area ratio, and cheek-to-jaw-width ratio. All three measures were significantly related to BMI in males, while the width-to-height and cheek to-jaw-width ratios were significantly related to BMI in females. In study 2, these images were rated for perceived weight by Caucasian observers. We showed that these observers use all three cues to judge weight in African and Caucasian faces of both sexes. These three facial cues, width-to-height ratio, perimeter-to area ratio, and cheek-to-jaw-width ratio, are therefore not only related to actual weight but provide a basis for perceptual attributes as well. PMID- 20301847 TI - Interactions among the effects of head orientation, emotional expression, and physical attractiveness on face preferences. AB - Previous studies have shown that preferences for direct versus averted gaze are modulated by emotional expressions and physical attractiveness. For example, preferences for direct gaze are stronger when judging happy or physically attractive faces than when judging disgusted or physically unattractive faces. Here we show that preferences for front versus three-quarter views of faces, in which gaze direction was always congruent with head orientation, are also modulated by emotional expressions and physical attractiveness; participants demonstrated preferences for front views of faces over three-quarter views of faces when judging the attractiveness of happy, physically attractive individuals, but not when judging the attractiveness of relatively unattractive individuals or those with disgusted expressions. Moreover, further analyses indicated that these interactions did not simply reflect differential perceptions of the intensity of the emotional expressions shown in each condition. Collectively, these findings present novel evidence that the effect of the direction of the attention of others on attractiveness judgments is modulated by cues to the physical attractiveness and emotional state of the depicted individual, potentially reflecting psychological adaptations for efficient allocation of social effort. These data also present the first behavioural evidence that the effect of the direction of the attention of others on attractiveness judgments reflects viewer-referenced, rather than face-referenced, coding and/or processing of gaze direction. PMID- 20301848 TI - Time to learn: evidence for two types of attentional guidance in contextual cueing. AB - Repetition of the same spatial configurations of a search display implicitly facilitates performance of a visual-search task when the target location in the display is fixed. The improvement of performance is referred to as contextual cueing. We examined whether the association process between target location and surrounding configuration of distractors occurs during active search or at the instant the target is found. To dissociate these two processes, we changed the surrounding configuration of the distractors at the instant of target detection so that the layout where the participants had searched for the target and the layout presented at the instant of target detection differed. The results demonstrated that both processes are responsible for the contextual-cueing effect, but they differ in the accuracies of attentional guidance and their time courses, suggesting that two different types of attentional-guidance processes may be involved in contextual cueing. PMID- 20301849 TI - Memory for time distinguishes between perception and action. AB - Our experience of time is unlike that of other features of the sensory world such as colour, movement, touch, or sound because there is no unique receptor system through which it is received. However, since time can be perceived, remembered, estimated, and compared in a way analogous to other sensory experiences, it should perhaps be subject to some of the same architectures or principles that have advanced understanding in these other domains. By adapting a task designed to test visual memory within a perception/action framework we investigated whether memory for time is affected by the use to which temporal information is put. When remembering a visual or auditory duration for subsequent motor production, storage is biased by a delay of up to 8 s. When the same duration is remembered for subsequent perception, however, there is no such effect of delay on memory. The results suggest a distinction in temporal memory that parallels the perception/action dichotomy in vision. PMID- 20301850 TI - Light location influences the perceived locations of internal sounds. AB - Numerous studies have shown that visual stimuli can bias the perceived location of auditory stimuli. Here, we sought to determine if a visual stimulus can also bias the perceived location of multiple internal auditory stimuli. Fifty subjects were presented with a train of eight binaural click-pairs over headphones while a single flash of light was presented either to the left or to the right side of a central fixation point on an otherwise black CRT screen. A no-flash baseline was also implemented, as was a no-fixation control. The subjects used a rating scale to indicate the perceived location of each of the eight click-pairs within their heads. The results showed that the flash of light significantly influenced the perceived location of the click-pairs, biasing them in the same direction as the flash of light. This suggests that, even without perceptual correspondence, cross modal interactions can occur. PMID- 20301851 TI - The phantom in the mirror: a modified rubber-hand illusion in amputees and normals. AB - The bodily boundaries in amputees may seem to be more malleable than in non amputees, given the propensity for a phantom limb to embody a mirror-reflected hand. However, in the present investigation, in which phantom-limb illusions within body space are induced and manipulated, we found that perceiving phantom sensations and illusory embodiment does not require amputation. Surprisingly, in the present modified rubber-hand illusion, we found that simultaneous stroking or stimulation of the participant's target hand was not necessary to induce illusions of embodiment and corresponding perceptual illusions. We tested this upper-limb paradigm in fourteen upper-limb amputees and twenty-six controls (including fourteen lower-limb amputees). We propose a model for embodiment of a rubber or real hand passively observed in a mirror. In this model, passive observation of the hand in the mirror triggers body representations (body image and body schema), most likely through activation of the posterior parietal cortex and temporo-parietal junction. Activity in these regions heightens awareness of peripersonal space and increases tactile sensitivity, and may subsequently enhance perception of illusory touch and embodiment. Furthermore, sense of embodiment may be more apparent to the participant when the hand is threatened; however, embodiment may even be strengthened when the motor system is engaged, evoking motor schemata to support the more easily induced perceptual embodiment via body image. PMID- 20301852 TI - Long-term adaptation to neck/shoulder pain and perceptual performance in a hand laterality motor imagery test. AB - The effect of neck/shoulder pain on the performance in a hand laterality motor imagery test was studied. Responses to the Cooper and Shepard (1975, Journal of Experimental Psychology: Human Perception and Performance 104 48-56) hand laterality test were explored in twenty-four individuals with chronic non specific neck pain and twenty-one subjects with chronic neck pain of traumatic origin (whiplash-associated disorder). Twenty-two controls were also included in the study. Digitalised right- or left-hand stimuli were presented at five different stimulus angles (0 degrees, 45 degrees laterally, 90 degrees laterally, 135 degrees laterally, and 180 degrees). The experimental task was to decide the laterality as fast and accurately as possible. The performance, both reaction time (RT) and accuracy, of the two experimental groups was contrasted with that of the control group. The main results revealed that the subjects afflicted with whiplash injury on the average exhibited a faster response pattern than symptom free healthy controls. Despite their musculoskeletal deficits and experience of pain these volunteers also exhibited a preserved speed-accuracy tradeoff. Longer duration of time with symptoms of neck pain was, moreover, associated with progressively faster RTs. These results point to perceptual learning and may reflect different stages of adaptation to neck pain. PMID- 20301853 TI - "She's a waterfall": motion aftereffect and perceptual design in video games involving virtual musicianship. AB - A particularly unpleasant version of motion aftereffect was revealed after extensively playing proprietary video games in which the task is to co-ordinate spatially distributed responses in time with music. During playing, key musical and rhythmic phrases descend as coloured shapes from the top of the screen. After playing, static text is presented that appears to slide upwards, reflecting a neural reaction contrary to the falling shapes. The game both serves as a contemporary example of motion aftereffect and also highlights certain cross modal associations between space, time, and sound in the design of stimulus response relations. PMID- 20301854 TI - Forcing free fusion of stereograms. AB - n order to read articles that either are on stereopsis, or use stereopsis as a tool, it is virtually inescapable to learn to fuse stereograms without the help of a stereoscope or special glasses (free fusion). For a few, this is easy. For many, it is frustratingly difficult, leading some to turn their backs on stereopsis altogether. Here, we show how presenting a stereogram on a transparency-rather than on paper-with a fixation cross behind it (for uncrossed fusion), or presenting a fixation cross on a transparency with a paper stereogram behind it (for crossed fusion), can force free fusion towards greater success. PMID- 20301855 TI - Why are mixed-race people perceived as more attractive? AB - Previous, small scale, studies have suggested that people of mixed race are perceived as being more attractive than non-mixed-race people. Here, it is suggested that the reason for this is the genetic process of heterosis or hybrid vigour (ie cross-bred offspring have greater genetic fitness than pure-bred offspring). A random sample of 1205 black, white, and mixed-race faces was collected. These faces were then rated for their perceived attractiveness. There was a small but highly significant effect, with mixed-race faces, on average, being perceived as more attractive. This result is seen as a perceptual demonstration of heterosis in humans-a biological process that may have implications far beyond just attractiveness. PMID- 20301856 TI - Social determinants of cardiovascular health and disease. PMID- 20301857 TI - Duty to warn and genetic disease. AB - In this clinical column, we discuss the ambiguous distinction between genetic research and clinical genetics, particularly for Mendelian diseases with high recurrence risk, high morbidity and/or mortality and the possible amelioration of such diseases by screening or treatment. We use arrhythmogenic right ventricular cardiomyopathy as an example of a lethal Mendelian disorder, which prompted the discussion contained in this column. Working with such diseases may mean that genetic researchers have some responsibility for both immediate research subjects and their extended families, as they obtain molecular genetic information. For some diseases, therefore, a willingness to accept genetic research results should be an inclusion criterion, and it may be considered unethical for research ethics boards to approve genetic studies unless measures to ensure clinical follow-up have been established. We recommend managing the tensions between genetic research and clinical practice by using disease-based genetic registers, organized within a clinical genetic service. PMID- 20301858 TI - Validity and reliability of a Swedish version of the Relationship Assessment Scale (RAS): a pilot study. AB - BACKGROUND: There is a need for a short and easily administered scale, in the Swedish language, for assessing partner relationships in the health care of persons with cardiac disease. PURPOSE: To establish the reliability and validity of the Swedish version of the Relationship Assessment Scale (RAS). DESIGN: The present pilot study has a methodological design. FINDINGS: Content validity has been tested for relevance, clarity and readability. The scale was tested for construct validity with explorative factor analysis. The reliability was tested by internal consistency and test-retest analysis. The result showed a two-factor solution, which does not correspond to the original proposed one-factor solution. The factor analyses revealed two quite distinct factors of RAS, labelled "Relationship built on expectations and satisfaction of needs" and "Relationship built on love and devotion". CONCLUSIONS: The scale has satisfactory psychometric properties in terms of content validity, construct validity, homogeneity and stability in a population of persons with cardiac disease. Wider evaluations of the RAS for other populations and settings are recommended. PMID- 20301859 TI - Did you know ? ...NPO after midnight is not best practice. PMID- 20301860 TI - The art of medicine. PMID- 20301861 TI - Health care reform--one doctor/citizen's opinion. PMID- 20301862 TI - Nursing care partnership program: project summaries. PMID- 20301864 TI - Moulding the next generation of researchers. PMID- 20301863 TI - In conversation about nursing research. PMID- 20301865 TI - Opening new doors. PMID- 20301866 TI - Finding a niche in research. PMID- 20301867 TI - Nursing research wants its due. PMID- 20301868 TI - Some early thoughts on Spring. PMID- 20301869 TI - Pregnancy: a stress test for future health. PMID- 20301870 TI - First-trimester genetic diagnosis: a series of six cases. AB - A first-trimester screen consists of a nuchal translucency (NT) ultrasound measurement as well as maternal serum testing for pregnancy-associated plasma protein-A (PAPP-A) and human chorionic gonadotropin (hCG). An increased nuchal translucency (NT) thickness at 11 to 14 weeks gestational age is a common finding for Down syndrome, Trisomy 18 and cardiac defects. We present a series of six patients, four with NT measurements greater than the 95th centile, and two additional cases where the NT was normal, but maternal serum biochemical markers were unusual. All six of these cases had a chromosome anomaly or another genetic condition: Noonan syndrome, triploidy, Down syndrome, Trisomy 18, Turner syndrome and a rare chromosome abnormality known as Ring 18-Monosomy 18. Our series underlines the fact that it is important to explore other genetic and chromosome abnormalities, in addition to Down syndrome and Trisomy 18, when there is an abnormality on a first-trimester screen. PMID- 20301871 TI - Nonunion of a distal tibial stress fracture associated with vitamin D deficiency: a case report. AB - Nonunions of fractures occur infrequently and can be multifactorial. Some predisposing factors include fracture instability, poor vascularity and inadequate fracture reduction. The role of metabolic bone disease and endocrine abnormalities in nonunions is often overlooked. This article reports a case of a tibial nonunion associated with vitamin D deficiency. The diagnosis and treatment of the nonunion and endocrine abnormality is discussed. This case illustrates the importance of a multidisciplinary approach in this increasingly common endocrine condition. PMID- 20301872 TI - Examining patient beliefs: a step in physician-patient communication about medicines. PMID- 20301874 TI - Quality focus: Physicians remain the foundation of health improvement. PMID- 20301873 TI - Extenuating circumstances: The white coat ceremony--symbolism and promise. PMID- 20301875 TI - Scope of practice: overly cautious or professional vigilance? PMID- 20301876 TI - Movie smoking, movie horror, and urge to smoke. AB - It is known that exposure to smoking cues increases urge to smoke (UTS), but little is known about other media factors that might also increase UTS. We hypothesized that horror/ thriller movies might also increase UTS by increasing negative affect. We surveyed 536 movie patrons who were smokers aged 18 years or older. Subjects had exited 26 movies, of which 12 contained smoking and two were horrorfilms, one with and one without smoking. We used random effects regression to assess the association between exposure to movie smoking, movie horror, both and UTS, controlling for confounding factors. Median age was 26 years and 52% were female. Mean UTS was 5.9, 6.6, 6.6, and 8.7 for smokers exiting movies without smoking, with smoking, horror without smoking and horror with smoking respectively. Smoking in movies was associated with a significantly higher UTS (0.63 [95% CI 0.31-0.94]). Horror with smoking increased UTS by 2.8 points (95% C.I. 2.3, 3.5); the horror without smoking estimate was 0.88, but not statistically significant. This short report offers preliminary evidence that movie horror as one factor besides visual smoking cues that could increase UTS in a community setting. PMID- 20301877 TI - [Clinical condition of the newborn versus tobacco smoke exposure during fetal life]. AB - The aim of this work was the assessment of the clinical condition, birth weight, frequency of premature birth and incidence of intrauterine growth restriction (IUGR) of the newborns whose mothers were active and passive smokers. This was a prospective study conducted in a group of 147 newborns born during the years 2003 2004 in the Princess Anna Mazowiecka Hospital, Warsaw, and hospitalized in the Neonatal and Intensive Care Department of Warsaw Medical University. Based on a questionnaire identifying the exposure to tobacco smoke and cotinine concentration in the mother's urine, the newborns were assigned to three groups: the newborns whose mothers were active smokers, the newborns whose mothers were passive smokers and the newborns of non-smoking mothers. There were no statistically significant differences in the Apgar score assessment at the 1st and 5th minute between the three groups of the newborns. Acid-base balance parameters (pH, BE) were also similar. The birth weight of the newborns of mothers who were active smokers was 325g lower than the birth weight of the newborns of non-smoking mothers. This difference was statistically significant p = 0.033. Maternal smoking in pregnancy was associated with an increased risk of deficit in birth weight 2.6 (1.0-6.9, CI 95%). In the group of the newborns whose mothers were active smokers, the incidence of lower birth weight (< 2500g) was also statistically significantly higher p = 0.01. There were no statistically significant differences in the incidence of premature birth and intrauterine growth restriction (IUGR). PMID- 20301878 TI - [Prenatal and postnatal child exposure to environmental tobacco smoke]. AB - The aim of the study was to evaluate the prenatal and postnatal child exposure to environmental tobacco smoke. The study population consisted of 83 women from Lodz, Poland among which detail questionnaire was conducted three times during pregnancy period. From all women included into the study the saliva sample was collected to verify smoking status in pregnancy. One year after delivery the second questionnaire was performed and urine sample from all children was collected. The cotinine level in saliva and urine was analyzed using Liquid Chromatography with Tandem Mass Spectrometry (LC-MS/MS ESI+). About 22% of the children were expose to ETS during prenatal and 46% in postnatal period. Cotinine level in children's urine statistically differentiated children from smoking mothers (Geometric Mean (GM) 11.4 ng/ml; 95% CI 7.1-18.3) and exposed homes (GM 7.3 ng/ml; 95% CI 3.6-15.0) compared with non-exposed homes (GM 1.3 ng/ml; 95% CI 0.9-1.7) (p < 0.001). Children should be more protected from ETS exposure in prenatal and postnatal period. PMID- 20301879 TI - [Preconceptional cigarette smoking and other risk factors for giving birth to a child with orofacial cleft]. AB - Evidence suggests an association between orofacial clefts and maternal smoking, common cold, and stressful life events. 247 mothers of children with an orofacial cleft completed a self-administered survey with questions concerning obstetric history. Of these, 29.6% were smokers in pre-conceptional period. 6.3%, 5.2% and 25.2% of participants reported working exposure to solvents, stressful life events, and common cold in the early pregnancy, respectively. Differences were seen between smokers and non-smokers for preconceptional folic acid supplementation (5.6% vs. 19.9%), multivitamin use (2.8% vs. 6.4%), pre conceptional health care utilization (15.3% vs. 30.4%), and late enrollment for prenatal care (> 12 weeks of gestation; 6.2% vs. 1.9%). Improved lifestyles of women of childbearing age is required. PMID- 20301880 TI - [The effect of tobacco smoking on clinimetric evaluation of stroke patients]. AB - Tobacco smoking is recognized as the risk factor of stroke, however its effect on the risk of recurrent cerebrovascular events is not well clarified. THE AIM OF THE STUDY: To evaluate the effect of tobacco smoking on results of clinimetric scoring of stroke patients and association with results of routine laboratory tests. The study included 431 stroke patients (409--ischemic stroke, 22--with hemorrhagic transformation of ischemic stroke). After admission to Emergency Room all stroke patients were examined clinically and scored according to National Institute of Health Stroke Scale (NIHSS). Then, 7 days after stroke onset NIHSS scoring was repeated and patients were scored in Rankin and GOS scales (Glasgow Outcome Scale). Everyday activity was assessed in Barthel scale 30, 90, 180 and 360 days after stroke onset. Moreover, computer tomography scans and laboratory tests were performed including hematology, glucose, fibrinogen, CRP and D-dimers concentrations. In smokers with ischemic stroke we have found trend (p = 0.0695) in decreasing of NIHSS scoring in comparison with non-smokers. The assessment in Rankin scale performed 7 days after stroke onset showed better neurological state of smokers with stroke (p < 0.01) in comparison with non-smokers and in ex smokers with ischemic stroke (p < 0.05) comparing to non-smokers. Smokers with stroke (ischemic and with hemorrhagic transformation) had higher (p < 0.01) scoring in GOS 7 days after onset of symptoms in comparison with non-smokers. Ex smokers with ischemic stroke had higher (p < 0.05) scores in GOS than nonsmokers. Tobacco smoking had no effect on clinimetric evaluation of patients with hemorrhagic transformation of ischemic stroke. Smoking was associated with lower levels of glucose, fibrinogen and D-dimers and higher hematocrit in ischemic stroke patients. CONCLUSIONS: The clinical course of the early phase of ischemic stroke was benign in smokers comparing to non-smokers. Better results of clinimetric evaluation and lower mortality of smokers with ischemic stroke may be related to lower levels of glucose, fibrinogen and D-dimers. Tobacco smoking had no effect on long-term clinimetric evaluation of patients both with ischemic stroke and hemorrhagic transformation. In smokers with hemorrhagic transformation higher mortality was associated with increased D-dimers concentration. PMID- 20301881 TI - [The smokers voice self assessment based on Voice Handicap Index (VHI)]. AB - Complex voice assessment due to European Laryngeal Society proposals (2000) contains voice self estimation based on the Polish version of the Voice Handicap Index (VHI). This study focuses on the relation between voice handicap and smoking in dysphonic patients, who are using voice professionally. Thirty outpatient (25 female and 5 male, aged 40 to 55 years) voice department attendees suffering from professional dysphonia took part in this study. All patients after phoniatric examination completed the Polish version of the Voice Handicap Index (VHI). The questions concern functional, emotional and physical complains due to dysphonia. Most of smokers did not complain of dysphonia related problems comparing to non smokers. Even the scores of functional and emotional scales of VHI in smokers shown better results (less handicap) than in nonsmokers. Smoking does not affect patients handicap due to dysphonia measured in the Voice Handicap Index. PMID- 20301882 TI - [Impact of cigarette smoking on the clinical outcome of Crohn's disease]. AB - Cigarette smoking is a well known independent risk factor for a more severe course of Crohn's disease, but individual factors determining this impact are poorly known and it is not evident if smoking cessation is associated with an improvement in the disease activity. The aim of our study was to assess the factors determining the harmful impact of smoking in individuals with Crohn's disease. A total of 148 consecutive patients with Crohn's disease and Crohn's disease activity index < 200 were enrolled in a prospective 12-18 month study. Patients were classified into three groups as: current smokers, former smokers, and nonsmokers. Body mass index, alcohol consumption, oral contraceptive use and blood lipid levels were also recorded. The main outcome measure was the rate of fare-up. We observed the flare-up developement in 38% current smokers, versus 21% non-smokers and 26% former smokers. The relative risk of flare-up adjusted for confounding factors was 1.37 (1.09 +/- 1.96) in current smokers. Obesity, dyslipidaemia, and alcohol consumption had no significant effect. Current smoking, particularly heavy smoking, significantly increases the risk of flare-up in Crohn's disease patients. Former smokers have a risk similar to that of non smokers. PMID- 20301883 TI - [Does spironolactone use at arterial hypertension therapy protect endothelium also in smoking patients?]. AB - The aim of the study was evaluation of spironolactone effect on concentration of endothelin-1 (ET-1 - vasoconstrictive substance produced by endothelial cells) and aldosterone (Ald) and plasma renin activity (PRA) in patients with primary arterial hypertension (AH): group A--smoking patients (11 individuals) in comparison with group B--non-smoking ones (12 individuals). ET-1, Ald and PRA were assessed before treatment (examination 1) and after 20 days of spironolactone therapy in dose 25 mg/day (examination 2). We observed: In group A significant elevation of: ET-1 ((Me +/- S exam.1 - 45.55 +/- 12.95 vs. exam.2 - 63.41 +/- 12.71 pg/ml, p = 0,009) PRA (Me +/- S exam.1 - 1.8 +/- 0.78 vs. exam.2 3.0 +/- 1.41 ng/ml/h, p = 0,012). In group B: significant decrease of ET-1 (Me +/- S exam.1- 61.58 +/- 12.15 vs. exam.2 - 43.48 +/- 14.37 pg/ml, p = 0.0028) significant elevation of PRA (Me +/- S exam1 - 1.20 +/- 1,91 vs. exam2 - 2.51 +/- 1.78 ng/ ml/h, p = 0.028).In our investigation different action of spironolactone on ET-1 in the two groups was observed. In group B spironolactone decreased ET-1 but in group A we noticed elevated ET-1 concentration. These results indicate advantageous endothelial effect of spironolactone only in non-smoking patients with AH. PMID- 20301884 TI - [Smoking and periodontal disease of adolescents--results of an epidemiological survey]. AB - A questionnaire concerning oral health designed for young people aged between 15 and 18 and based on one produced by Tokyo University entitled Medical Outcome Study (MOS) and Oral Health Score (OHS) 8020, was submitted to a group of Polish citizens. One of the 10 questions in the OHS part of the questionnaire concerned smoking habits. 296 persons (157 girls and 139 boys) living in west Poland, took part. For a clearer evaluation of the health habits in this group, a comparison was made between the youngest (15 y old) and oldest (18 y old) groups. The Oral health Score (with a possible maximum 20 points) for the examined group was 14.4 which is one of the lowest among evaluated European countries. Smoking was most frequent among the 18 year olds (20.1%) whereas among the respondents in the younger group it was this value (16.5%). Moreover, in age 15 group, boys (29%) were more often smokers than girls (5.5%); 22% of 18 year old girls and 19.8% of boys smoked. Comparing the answers relating to oral health with the frequency of smoking revealed a connection between this habit and the presence of periodontal disease. Smoking increases a risk of developing periodontal disease. According to the results there is a need to increase an oral health education and identification of risk factors such smoking among Polish adolescents. PMID- 20301885 TI - [State of dentition and the index of dental decay treatment in smokers and non smokers]. AB - The aim of the study was evaluation of the state of dentition and the efficiency of dental decay treatment in smokers and non-smokers as well as defining whether dentists and family doctors inform their patients about the negative influence of tobacco smoking on their health state. The studies were conducted among 64 people, 35 men (54.69%) and 29 women (45.31%). Cigarette smoking was reported by 26 people (40.63%). The mean age of nonsmokers was 37.87 and smokers 39.04%. In the smokers group the value of mean number D denoting the number of carious teeth was 6.23; the mean number M denoting the number of missing teeth had the value of 9.85, in non-smokers 4.66 and 6.29 respectively. In smokers the value of mean number F denoting the number of filled teeth was 4.46 and in non-smokers 7.39 (p< 0,01). The mean number DMF in smokers had the value of 20.54, in non-smokers 18.34. The state of dentition in smokers was distinguished by greater number of carious and missing teeth and smaller number of filled teeth. In non-smoking patients the efficiency of dental decay treatment was higher in comparison with the group of non-smoking people (p < 0.05). Dentists informed 35.94% of the surveyed about the harmfulness of cigarette smoking whereas family doctors informed 29.69% of them. It is necessary to conduct thorough studies to define the influence of cigarette smoking on oral health as well as to inform all patients about the negative influence of cigarette smoking on their health state. PMID- 20301886 TI - [The influence of tobacco smoking on the state of dentition and the effect of the chronic periodontitis conservative treatment in periodontology clinic patients at the Chair and Department of Periodontology of the Medical University in Lublin]. AB - Tobacco smoking is a serious health and social problem. The aim of the study was investigation of the influence of tobacco smoking on the state of dentition and effects of conservative treatment of the chronic, moderately advanced periodontitis by comparison of API, SBI, PPD and CAL indices before and after the treatment in smoking and non-smoking patients. Smokers group consisted of 30 people aged 30-48 including 15 men and 15 women who had smoked for more than 10 years, with the intensity of smoking of more than 10 cigarettes a day. The control group constituted 30 non-smoking people aged 30-50; 15 men and 15 women. The SBI index of bleeding from periodontal pockets in smokers is essentially statistically lower than in non-smokers, with similar hygiene indices. Shallowing of periodontal pockets depth (PPD) after the treatment is smaller than in smokers. Reconstruction of alveolodental ligament measured with CAL index in smokers seems to be smaller than in non-smokers. PMID- 20301887 TI - [Functional and health conditions of elderly smokers]. AB - Research conducted for many years, on smoking harm has revealed a connection between using nicotine and numerous disorders affecting human beings. Nowadays 33% of Poles smoke, 11-25% of the elderly smoke. There are plentiful anti-smoking campaigns aimed at the young and those in their reproductive years. Such campaigns addressed to the elderly are a seldom occurrence. The aim of this work was to analyze the actual functioning and health of smokers aged 65 and more living in various surroundings. The research involved a group of 300 individuals aged more than 65: older people home residents--100 individuals, veteran home residents--100 individuals and the University of the Third Age students--100 individuals. The tool utilized in the course of the research was a questionnaire concerning smoking, diseases affecting the subjects, medication taken and personal information. Assessment of a functional state, physical activity, mental state and health was carried out with the help of General Geriatric Assessment questionnaires. In the researched group, the frequency of smoking was 11.3%, 18.1% among men, 9.2% among women. The average age of the smokers was 70.6 +/- 5.6, the average age of the non-smokers was 75.5 +/- 7.0 .The average number of cigarettes smoked was 11.3 +/- 7.3 a day. The older the subjects of the research, the smaller percentage of the smokers among them as well as the fewer cigarettes smoked. The smokers indicated a substantially higher MMSE result, Tinetti, lower BMI, lower percentage of fat, lower frequency of being affected by cataract or urinary incontinence and a larger number of lung conditions. In the researched groups both in the older people home and veteran home residents, the smokers are younger, better educated, more fit, better nourished, possessing a larger mental capacity and hand strength as compared to the other members of a given community. Among the University of the Third Age students no significant differences between the smokers and non-smokers were observed. The smallest percentage of the smokers is among the University of the Third Age students (9%), the largest among the older people home residents (14%). The most cigarettes are smoked by the University of the Third Age students, the fewest by the older people home and the veteran home residents. Women smokers constitute majority among the University of the Third Age students whereas there are more men smokers among the older people home and the veteran home residents. There is a distinct need of organizing anti smoking campaigns aimed at the elderly taking into account the area of their functioning. PMID- 20301888 TI - [Changes in tracheal ciliated epithelium of rats exposed to environmental tobacco smoke--experimental studies]. AB - It has been already proved in many experimental studies that tobacco smoke has multiple toxic effects on respiratory tract cells. Alterations in ciliary epithelium of rats trachea after short exposition to high tobacco smoke concentrations in inhaled air were been determinate in current study. Morphological evaluation revealed in lining epithelium voluminous exudate located between epithelium and lamina propria cells with evidently larger number of mast cells. PMID- 20301889 TI - [Development of analytical method for determination nicotine metabolites in urine]. AB - The assay of biomarkers in biological material is the most popular and reliable method in estimate exposure to tobacco smoke. Nicotine and its metabolites qualify to the most specific biomarkers for tobacco smoke. Currently the most often used are cotinine and trans-3'-hydroxycotinine. The aim of this study was development of easy and quick method of determining nicotine and its main metabolites with high performance liquid chromatography--available in most laboratories. Nicotine and its metabolites in urine (cotinine, trans-3' hydroxycotinine, nornicotine and nicotine N-oxide) was determined by means of high performance liquid chromatography with spectrometry detection (HPLC-UV). The determined compounds were extracted from urine by means of the liquid-liquid technique, before analysed by the HPLC method. Developed technique of high performance liquid chromatography proved to be useful to assessment nicotine and its four metabolites in smokers, though further research are necessary. The further modification of procedure is required, because of the interferences of cotinine N-oxide with matrix, which prevent determination. Increasing the efficiency of extraction nicotine and nornicotine could enable the determination in people exposed on environmental tobacco smoke (ETS). This study confirm other authors' observations that 3'-hydroxycotinine might be equivalent with cotinine predictor of tobacco smoke exposure, however further studies are required. PMID- 20301890 TI - [Impact of tobacco smoking on biologic background of laryngeal squamous cell carcinoma]. AB - The most common risk factors related to the occurrence of laryngeal cancer is related to tobacco smoking. It is interlinked to the presence of chemical substance in tobacco smoke. These substances are mutagenic factors and they are carcinogens. These substances penetrate cell, they penetrate cellular nucleus and in consequence, it causes damage to the genetic material. Accumulation of mutations enables cells to conduct local invasion, and it initiates tumor invasion and metastasis. We used tissue samples from 11 patients that were selected from all head and neck specimens and diagnosed at Department of Clinical Pathology in Bydgoszcz in 2008. We have made immunohistochemical staining in order to describe localization of MMP-2. Furthermore, the expression of proliferative antigens: PCNA and Ki-67 in laryngeal carcinoma and their relations to tumor invasion and metastasis were measured. We divided patients into two groups: people who smoke less than 20 cigarettes a day and people who smoke over 20 cigarettes a day. All patients were diagnosed with a squamous cell carcinoma with histological grade G2. Tumors were staged according to the TNM classification. Studied patients were classified ranging T2 - T4, N0 - N3 and all were M0. We found out similarities in expression of analyzing antigens in individual groups of patients. We observed decreased expression of MMP-2, PCNA and Ki-67 amongst patients who smoke less than 20 cigarettes a day in comparison with patients who smoke more than 20 cigarettes a day. We noticed such trend in tumor cells and in dysplastic cells. We certify differences between levels of expression of researched markers according they intensity of exposure on tobacco smoking. Probably those differences may represent different levels of cell damage. PMID- 20301891 TI - [Mutations of tumor suppressor gemne TP53 in tobacco smoke-associated tumors]. AB - Tumour suppressor gene TP53 is a subject of frequent lesions and mutations in a majority of cancer types that is followed by its dysfunction in regulation of cell proliferation, apoptosin and DNA repair. Mutation profile reflects the presence of mutagen-vulnerable sites (including tobacco smoke carcinogens) in its structure. A number of mutations in tobacco smoke-associated cancers are higher than in other types. Particularly, G > T mutation is recognized a signature to benzo(a)pyrene exposure. Further, a mutation profile is dependent on cancer anatomic localization and histological type. There were put forward suggestions concerning estimation of cancer risk and disease prognosis basing of TP53 gene status and expression. The protocols of gene therapy involving TP53 gene are still not satisfactory. PMID- 20301892 TI - [Significance of Arg554Lys AHR gene polymorhism an survival of in squamous cell carcinoma laryngeal cancer in relation to tobacco smoking--preliminary study]. AB - Initiation and progression of laryngeal cancer is associated with tobacco smoking and abusing of strong alcoholic beverages. A significance of genetic factor, although not defined sufficiently yet has been raised as well. The studies were focused on an influence of AHR gene polymorphism on survival of squamous cell carcinoma laryngeal subjects. The study material was 65 archival DNA samples analyzed by RLP-PCR. The samples varying with electrophoretic mobility were DNA sequenced. In the study group 9 heterozygotic variants Arg554Lys (codon 554) were detected. One case was a carrier of two other mutations in codon: 490 (1468 A > G) and 570 (1708 G > A). Survival time, metastasis and occurrence of second primary tumors were compared in carriers of wild type and Arg554Lys variant AHR. Preliminary results indicate for a necessity of further studies as until now the study group is too small to find a conclusive association. PMID- 20301893 TI - [The effect of cigarette smoking on serum concentration of conjugated dienes in stroke patients]. AB - Exposition to tobacco smoke as a source of free radicals leads to stimulation of lipids peroxidation. Oxidation of low-density lipoproteins (LDL) increases the risk of stroke. Aim of the study was to evaluate the effect of cigarette smoking on the serum concentration of conjugated dienes as markers of peroxidation of fatty acids. In the study participated 431 subsequent stroke patients (ischemic and with hemorrhagic transformation) hospitalized in Department of Neurology in Poznan in a period from February 2007 to may 2008. The control group consisted of 16 healthy, non-smoking volunteers. The concentration of conjugated dienes (CD) in patients' sera was estimated by spectrophotometric methods. Furthermore, lipid profile, glucose level, concentration of C-reactive protein and white blood cells count were analysed. We have also calculated waist- to hip ratio. Serum concentrations of conjugated dienes were increased both in smoking and non smoking patients with ischemic stroke. We noticed negative correlation between conjugated dienes levels and tobacco smoking duration in patients with ischemic stroke (Kendall's tau = -0.154, p = 0.0474). Moreover, conjugated dienes concentration correlated positively with triacylglycerides levels in smokers with ischemic stroke (rSpearman = 0.198, p = 0.0452; Kendall's tau = 0.135, p = 0.0428). The abnormalities in concentrations of conjugated dienes in ischemic stroke patients resulted rather from disturbances of cerebral circulation, than from cigarette smoking itself. Hypertriglyceridemia in smokers with ischemic stroke causes up-regulation of lipids peroxidation. The rate of production of conjugated dienes is associated with distribution of adipose tissue reflected by waist to hip ratio. PMID- 20301894 TI - [The effect of cigarette smoking on serum activities of paraoxonase and arylesterase in stroke patients]. AB - Cigarette smoking is one of most important modifiable risk factors of stroke. Lipids peroxidation remains crucial among pathomechanisms leading to increased risk of stroke in tobacco smokers. AIM OF THE STUDY: To evaluate the effect of cigarette smoking on the activity of paraoxonase and arylesterase as enzymes involved in protection against oxidation of low-density lipoproteins. We have included in the study 431 subsequent stroke patients hospitalized in Department of Neurology in Poznan in a period from February 2007 to May 2008. The control group consisted of 16 healthy, nonsmoking volunteers. The activity of paraoxonase (PON) and arylesterase (ARE) in patients' sera was estimated by spectrophotometric methods. All patients admitted to emergency room underwent clinical examination. General examination, neurological examination and clinimetric assessment with the use of GCS (Glasgow Coma Scale) and NIHSS (National Institute of Health Stroke Scale) scales were performed. RESULTS: The group of ischemic stroke patients consisted of 26.7% current smokers, 31.3%--ex smokers, and 42% never-smokers. Among patients with hemorrhagic transformation of ischemic stroke 13.6 % actively smoked cigarettes, 22.7% were ex-smokers, and 63.7%--never-smokers. The statistical analysis of age of patients in all studied groups showed the younger onset of stroke in smokers (p < 0.0001). The activity of arylesterase was significantly disturbed by cigarette smoking in patients with ischemic stroke. In smokers with ischemic stroke ARE activity correlated negatively with number of cigarettes smoked daily (r = -0.2133; p = 0.0322). We have showed positive correlation of duration of smoking with ARE activity (r = 0.2573; p = 0.0239). In non-smoking ischemic stroke patients PON activity increased significantly (p < 0.01) comparing to controls. Tobacco smoking caused impairment of enzymatic antioxidant mechanisms related to paraoxonase activity, because there was no significant (p > 0.05) up-regulation of PON activity in smokers with ischemic stroke. The activity of arylesterase is modified by tobacco smoking in ischemic stroke patients. Smoking causes disturbances in paraoxonase- associated enzymatic antioxidant effects in ischemic stroke patients. Abnormalities of activities of antioxidant enzymes may cause earlier onset of stroke in tobacco smokers. PMID- 20301895 TI - [Lack of association between metabolic and antioxidant gene polymorphisms (GSTM1, GSTT1, CAT, MnSOD, GPX1) and maternal quitting of smoking in pregnancy- preliminary results]. AB - A number of genetic studies have been performed to find susceptibility genes for smoking behavior. Recently the polymorphism Mspl in CYP1A1 was reported to facilitate quitting of smoking during pregnancy. We aimed to determine whether polymorphisms of CAT (-330C > T), MnSOD2 (c. 47T > C), GPX1 (c599C > T), the null GSTM1 and GSTT1 are associated with smoking behavior in pregnant women. We found no significant differences in genotypes distribution between women who quit smoking in the first trimester of pregnancy and persistent smokers. Analyzed polymorphisms seems to not influence susceptibility to smoking in the investigated group of women. PMID- 20301896 TI - [Tobacco smoking by patients treat for alcohol addiction--interaction of psychoactive substances]. AB - Alcohol and tobacco addictions are often joined. There are biological and environmental reasons of the co-addiction. Active compounds present in the substances can interact in different ways, for example in biotransformation reactions. The aim of the paper was to describe differences of ethanol and nicotine metabolites concentrations in biological fluids. The material was blood and urine collected from alcohol and tobacco addicted patients treated in The Detoxication Department, Toxicology Clinic in Krakow. Acetaldehyde and volatile substances were determined in blood by GC-FID. Cotinine was determined in urine by HPLC-UV. Most (91.3%) of alcohol addicted patients were tobacco smokers. In the group 76.3% patients smoked more than 11 cigarettes per day. Tobacco addiction was usually longer or lasted the same time as alcohol addiction. Mean cotinine urine concentrations in the group of alcohol addicted smoking patients were lower than in group of smoking patients not alcohol addicted (p < 0.05). Differences between mean acetaldehyde blood concentrations in group of alcohol addicted smoking patients and alcohol addicted non smoking patients were not significant (p > 0.05). PMID- 20301897 TI - [Exposure to respirable suspended particles in smoking and non-smoking sections of pubs in southern Poland]. AB - Particulate matter (PM), including fine particulate matter (PM2.5), is one of the main pollutant which it damages of human health seriously. Tobacco smoke is significant source of PM2.5 in indoor microenvironments. New bill of complete smoking ban in all public places in Poland is currently under consideration in polish parliament. Proposed maximum allowed concentration of PM2.5 for all non smoking sections is 0.03 mg/m3. Concentrations of tobacco-specific fine particulate matter (PM2.5) were monitored in thirteen pubs located in southern part of Poland during winter season. All examined pubs had two types of sections: smoking and non-smoking. PM2.5 concentrations were monitored during one hour in each section using DustTrak monitor (TSI Inc., USA). The Wilcoxon matched pair test was used to compare pollutant concentrations in smoking vs. non-smoking sections. Average 1-hour PM2.5 concentration in smoking sections was 1.25 +/- 1.85 mg/ m3 and varied from 0.18 do 7.21 mg/ m3. Average 1-hour PM2.5 concentration in non-smoking sections was 0.35 +/- 0.29 mg/m3 and varied from 0.056 to 1.01 mg/m3. The highest temporary PM2.5 concentration of 25.5 mg/m3 was found in a pub located in cellar storey were with volume of 60 m3, 13 smokers and no air-condition. There was little difference in PM2.5 levels between smoking and non-smoking section. PMID- 20301898 TI - [Evaluation of the indication of carbon monoxide in exhaled air]. AB - In spite of intensified antitobacco campaigns and decrease in social acceptance for smoking it is still an important issue. In prevention there is a need to make smokers and non-smoking people aware of a level of exposure to tobacco smoke. One of the objective methods to evaluate this exposition is to measure a concentration of the carbon monoxide in exhaled air. The aim of our study was to evaluate the indication of carbon monoxide in exhaled air. The research was based on examination of 67 patients admitted to admission room in SP CSK, Warsaw. The level of carbon monoxide was measured with Smokerlyzer device in 56 cases (34 women, 22 men). Everyone in this group answered questions concerning a reason of admission to hospital, concomitant diseases, and addiction to smoking and ways of fight against the addiction as far as smokers are concerned. Current smokers answered also questions about their attitude to smoking and filled in Fagerstrom and Schneider tests. In a group of 67 patients 11 were not able to proceed the test with Smokerlyzer, 5 (45.5%) due to dyspnea, 4 (36.4%) due to lack of a verbal contact. In the group of 56 investigated patients 20 (35.7%) have never smoked, 32 (57.1%) were ex-smokers and 4 (7.1%) were current smokers. 3 (75%) of the smokers have tried to give up smoking 3 times on average. In the Fagerstrom test their mean came to 3.5 points, what indicates a low level of addiction. The Schneider test averaged out 8 points, what indicates a good motivation to give up smoking. The average of concentration of carbon monoxide in exhaled air came to 8 ppm (1.87% Hb) in this group. In the group of non-smoking patients the level of carbon monoxide came to 1.4 ppm (0.67%Hb). In the group of nonsmoking patients exposed to the tobacco smoke, the level of carbon monoxide came to 3 ppm (1.15%), but the difference was not statistically significant (p > 0.05). The increased CO level in exhaled air is usually caused by smoking cigarettes and exposure to ETS. All the smokers acknowledged the addiction. Routine use of Smokerlyzer in the admission room is limited, mainly by the dyspnea. Despite the practicality of CO level measurement, taking medical history of smoking is still the most important. PMID- 20301900 TI - [Electrophoretic pattern of alpha-amylase isoenzymes in serum of non-smoking and smoking normal persons and patients with pancreatitis]. AB - Recent epidemiological studies have shown the significant role of tobacco smoking in the development of chronic pancreatitis. It has been demonstrated that nicotine may also alter normal exocrine pancreatic function. However, the mechanism of development of these changes has not been fully recognised. In this pilot study we used a electrophoresis to compare the serum amylase patterns of healthy smokers and non-smokers. Amylase isoenzymes, separated into the pancreatic types by electrophoresis in agarose gel. Sample volume was 20 mL. The electrophoresis was at 4 degrees C temperature for 2 to 2.5 h. Amylase isoenzymes on agarose gels was localized by staining using the visualization system Phadebas Amylase Test. In serum normal non-smokers, I and II-type isoenzymes were predominant. III type izoenzyme was found in serum of smoking patients with pancreatitis. Total amylase activity in serum of smokers was slightly above normal. The isoenzymogram shows the presence of II and III-type isoenzyme, increase of isoenzymes activity. Earlier study III-type isoenzyme was found only in serum from cases of acute pancreatitis. In electrophoretic pattern of alpha amylase isoenzymes in serum of smoking normal persons and patients with pancreatitis was affirmed the additional form of izoenzmes of amylase, that provide damaging influence tobacco smoking on pancreas. PMID- 20301899 TI - [Estimation of optimal levels of tobacco biomarkers to distinguish active and passive smokers using ROC analysis]. AB - Many epidemiological studies on health consequences of tobacco smoke exposure require classification of examined subjects either as active or passive smokers. Receiver operating characteristics (ROC) curves are useful for organizing cut-off values of tobacco biomarkers and visualizing their performance. The cut-off values might be applied to distinguish cigarette smokers and persons involuntary exposed to second-hand tobacco smoke (SHS). Aim of the study was estimation of optimal levels of three biomarkers (cotinine, 1-hydroxypyren, and carboxyhemoglobin) to distinguish active and passive smokers using ROC curves. 98 subjects (62% females) were qualified to the study. Mean age was 40 +/- 12 years. Active smokers (n = 38) had an average smoking history of 9 +/- 8 years and declared smoking at least 5 cigarettes per day (mean 17 +/- 7). Passive smokers (n = 60) declared being exposed to environmental tobacco smoke either at home or work (n = 18) or other indoor microenvironments, where they spent some time during their daily activity (n = 42). Cut-off values were determined for each biomarker using ROC curves. Optimal cut-off values were: 327 microg/g creatinine for cotinine, 47 ng/g creatinine for hydroxypyren, and 1.27% HbCO for carboxyhemoglobin. Among three studied biomarkers, cotinine showed the best sensitivity of 97.4% and specificity of 90.0%. Carboxyhemoglobin showed sensitivity of 89.5% and specificity of 93.3%, whereas 1-hydroxypyren 76.3% and 78.3%, respectively. Analysis of ROC curves appears to be a way to distinguish active and passive smokers using various tobacco biomarkers. PMID- 20301901 TI - [Concentrations of serum bone turnover markers in smoking pregnant women and in umbilical cord blood of newborns]. AB - Smoking is proved to be harmful to many aspects of human health. In many papers lower bone mineral density and differences in bone metabolism in patients who smoke were shown. However, little is known about biochemical bone formation and resorption markers in women who smoke during pregnancy as well as in their newborn. The aim of the study was to assess whether the smoking during pregnancy has an effect on the serum levels of bone metabolism markers in maternal and umbilical cord blood. The study consisted of 43 pregnant women under surveillance at the Obstetrics and Gynecology Clinic of the Institute of Mother and Child in Warsaw. They were divided into two groups: smoking (n = 22) and nonsmoking (n = 21) pregnant women. The serum concentration of bone turnover markers (osteocalcin -OC and C-terminal telopeptide of type I collagen--CTX) were determined by immunoenzymatic method in maternal and umbilical cord blood obtained at the time of delivery. In the whole studied group concentration of bone metabolism markers were significantly higher in umbilical cord blood than in maternal blood. In umbilical cord blood mean concentration of osteocalcin was: 70.4 +/- 19.3 ng/ml whereas in maternal serum it was 16.6 +/- 5.8 ng/ml (p < 0.0001). Moreover, the level of the resorption marker CTX was 1.02 +/- 0.28 ng/ml and 0.71 +/- 0.24 ng/ml (p < 0.0001), respectively. In serum of both smoking and non-smoking mothers similar values of osteocalcin (17.9 +/- 7.1 ng/ml versus 15.3 +/- 3.8 ng/ml) and CTX (0.69 +/- 0.21 ng/ml versus 0.64 +/- 0.27 ng/ml) were observed. However, in umbilical cord blood of smokers, the concentration of OC was about 2 fold lower (p < 0.0001), while the CTX level was slightly higher than in the non smoking group. In both groups significant correlation (p < 0.0001) between concentration of CTX in mothers and their newborns were found. Our results indicate the negative influence of smoking during pregnancy on the fetal's bone formation process. This is reflected in lower osteocalcin level in umbilical cord blood and might be one of the causes of bone metabolism disturbances later during childhood and even in adult life. PMID- 20301902 TI - [The effect of tobacco smoking on nitric oxide serum concentration in pregnant women and umbilical cord blood]. AB - The aim of the study was to estimate the effect of tobacco smoking on serum nitric oxide (NO) concentration in pregnant women and umbilical cord blood and birth weight. We also examined the relation between serum NO and number of cigarettes consumed by mother. Forty healthy pregnant women patients of Clinical Department of Obstetrics and Gynecology, Institute of Mother and Child were divided into two groups: smoking and tobacco abstinent according to questionnaire declaration. The current smokers were defined as those who had smoked 5 cigarettes per day for 2 years before conception and continued smoking during pregnancy. Serum concentrations of nitric oxide were determined by colorimetric method using a commercially available kit Nitric Oxide NonEnzymatic Assay (Oxis International Inc, USA). We observed that the mean concentrations of nitric oxide in serum were similar on the beginning and the end of pregnancy. In group of smoking women these values decreased during pregnancy and were lower 10% in I and 20% in III trimester (p < 0.01) than in tobacco abstinent. In umbilical cord blood of infants born to smoking women level of nitric oxide was slightly lower than in non-smoking ones. In both studied groups the mean concentrations of nitric oxide in umbilical cord blood were higher than these observed in mothers in third trimester (in smoking 46% and in nonsmoking 17% respectively; p < 0.01). In smoking group we observed positive correlation between concentrations of NO in serum of mothers and cord blood of their newborns (r = 0.74; p < 0.01). Our analysis revealed negative correlation between number of cigarettes consumed and serum nitric oxide in smoking women (r = -0.52 in I trimester and r = -0.47; p < 0.05 in III trimester) as well as in their children (r = - 0.35; p < 0.05). Birth weight in infants born of smoking mothers was lower in average by 260 g as compared with non-smoking ones (p < 0.05). Our results indicate that tobacco smoking during pregnancy reduced serum nitric oxide concentrations in mothers and their children and correlated with number of cigarettes daily consumed. In smoking women lower concentrations of NO co-exist with smaller birth weight than in tobacco abstinent which may suggest correlation between these parameters. Further studies will be continued in larger group of matched maternal-cord pairs to confirm of this association. PMID- 20301903 TI - [Concentration of calcium ions in the saliva and the value of the pH of the saliva in female and male smokers]. AB - Dental decay is a pathological process of extrasomatic origin which leads to demineralization and proteolytic degradation of hard surfaces of a tooth susceptible to this disease. Saliva composition, including calcium ion concentration and its pH value, is of importance in the development of the carious process. Tobacco smoke contains toxic compounds which negatively influence oral health. The aim of the study was evaluation of the selected saliva components: protein concentration, Ca2+ concentration, pH value both in male and female smokers. The investigated group included 65 patients reporting for the treatment to the Department of Conservative Dentistry of Medical University in Lublin. In the investigated group male smokers constituted 15.38%, female smokers -20.00%, male nicotine abstinents 21.54% and female nicotine abstinent 43.08%. The study included both survey examinations of patients and biochemical examinations of the saliva. Mixed, non-stimulated saliva was used as a material for biochemical examinations. Ca2+ concentration and pH of the saliva were assayed with the use of Rapidlab 348 analyzer. Protein in the saliva was assayed with calorimetric method according to Lowry. Saliva was collected from smokers 10 120 minutes after smoking of several cigarettes. It was stated that Ca2+ and protein concentration as well as pH of the saliva were not correlated with sex and cigarette smoking or non-smoking. PMID- 20301904 TI - [Effect of combined exposure to ethanol and tobacco smoke on lipid peroxidation in rats]. AB - Usually, alcohol addicted persons smokes cigarettes. In the study, the effect of combined exposure to alcohol and tobacco smoke in alcohol addicted rats on liver peroxidation was evaluated. Alcohol abuse and its presence in blood did not influence the cotinine level, what indicates the lack of the importance of this factor in nicotine metabolism. Similarly, enzymatic markers of liver damage (AspAT, AIAT, ALP) did not change, what showed lack of hepatotoxic effect studied compounds in applied model of alcohol addiction and tobacco smoke exposure. Combined exposure to alcohol and tobacco smoke increases the level of lipid peroxidation in brain, liver and lungs however decreases in serum. In kidneys the results are not unambiguous. PMID- 20301905 TI - [Influence of age in content of trace elements in pharyngeal tonsils from exposure and unexposure children]. AB - This project is aimed to estimate the effect of passive smoke on the levels of selected trace elements (Ca, Mg, K, Na) in pharyngeal tonsils of children in several group of age (2-5 years, 6-9 years, 10-15 years). This trace elements were determined using ICP-AES method. It was concluded that the exposure to the cigarette smoke in pharyngeal tonsils is a factor producing the changes in the levels of essential elements: geometric mean of Ca was the highest in pharyngeal tonsils of children in 10-15 years old unexposure to ETS (410 microg/g). The least level of Ca - 281 microg/g was observed in this samples in the same group of age, but in children exposure by ETS. High levels of K was observed in pharyngeal tonsils of children exposure to passive smoking in all of group of age to comparison to unexposure by ETS. The greatest content - 27479 microg/g was in pharyngeal tonsils in exposure to ETS in 6-9 years old was observed, but the least - 16478 microg/g in 10-15 years old. Change of content of Mg was from 764 to 784 microg/g in samples from children exposure by ETS to comparison 720-744 microg/g in children unexposure by ETS. High level of Na was observed in pharyngeal tonsils from children exposure to ETS in all of group of age to comparison to unexposure. This study showed that the kind of interaction dependent on age and exposed by ETS. The changes of given elements were different for children passive smoking and no passive smoking in several group of age. PMID- 20301906 TI - [Trace elements concentration in pharyngeal tonsils from exposed and unexposed to ETS children in refer to sex and places of living]. AB - The aim of this study was investigation influence sex and place living (industrial region or village) to concentration of: Ca, K, Mg and Na in pharyngeal tonsils (n = 84) from children exposed and unexposed to tobacco smoke and analysis kind of interactions between trace elements. Determination of these elements contents were performed by ICP-AES. It was found higher concentrations of Ca and Na in pharyngeal tonsils from boys (389 microg//g) and girls (356 microg/g) unexposed to tobacco smoke to comparison to expose to ETS boys (304 microg/g) and girls (298 microg/g). Higher concentrations of Ca and Na was found in this samples from children unexposed on ETS, living in industrial area to comparison to unexposed to ETS children living in village region. Higher concentration of K and Mg was found in exposed to ETS girls and boys in comparison to unexposed to ETS children, and higher level of these metals were found in exposed to tobacco smoke children living in industrial region and village. PMID- 20301907 TI - [The important mean of passive smoking for lead and chromium content in deciduous teeth]. AB - In this work the changes of lead (Pb) and chromium (Cr) content in deciduous children teeth exposed on environmental tobacco smoking were presented. As the control group were given deciduous children teeth nonexposed on tobacco smoking in home. The content of lead in deciduous teeth was higher in non-exposed population (13.81 microg/g) than in passive-smoking population (12.28 microg/g) p < or = 0.005. The passive smoking has effect to less chromium content in deciduous teeth. The quotient of lead and chromium contents was higher in passive smoking boys and girls and different kind of deciduous teeth. PMID- 20301908 TI - [The influence of tobacco smoking on the occurrence of copper in hydroxiapatites of gallstones]. AB - The studies were carried out on the changes in copper content in concretions of gallstones which were taken from 146 women (49 smoking and 97 no smoking) and 24 men (11 smoking and 13 no smoking), respectively. The elemental composition of gallstones was determined with ICP-AES method (Inductively Coupled Plasma - Atomic Emission Spectroscopy). Studies on copper occurrence in concretions of gallstones showed the presence of its higher concentrations in case of smoking women (9.59 microg/g) and men (8.99 microg/g) in comparison with no smoking women (7.02 microg/g) and men (7.66 microg/ g). It was shown differences in pattern of changes of copper concentration in gallstones in case of smoking and no smoking women and men. PMID- 20301909 TI - [The assessment of exposure on passive smoking in obese children]. AB - The aim of this study was to assess the an exposure on passive smoking in 50 obese children (29 girls and 21 boys) aged 9-16 years. We use questionnaire and personal interview method to complete data about smoking style, time of external exposure on tobacco smoke, number of family members whose are smoked, and the pinion of children about smoking generally. In the all subjects only one - 15 years old girl, was smoked active. 34% of children had non-smoking parents, 24% of children had one smoking parent, both in 20%, three members of family were smoked in 10% of children, and 12% had four and more. Inside sub-group of children with smoking parent 30% of them declared that their parents never smoke in children present, 15% sometimes. More than 50% of parents always smoked in children companion. The mean time of exposure on tobacco smoke was assess on 4.4 +/- 3.7 hour per day. We found positive significant correlation between BMI and daily time of exposure on tobacco smoke in obese children (r = 0.30, p < 0.05). There are necessary to complete more data about the comparison of passive smoking and obesity especially in children and their health. PMID- 20301910 TI - [Tobacco smoking among girls in Poland between 1998 and 2008]. AB - There are numerous researches referring to tobacco smoking among girls in Poland. Unfortunately comparing their results and trends tracking is prevented by methodological differences, such as: sample selection, use of different research tools, way of conducting researches and analyzing their results. In this paper, on the basis of data collected from periodical studies conducted in Poland in the years 1998-2009 on the representative samples of adolescents, the estimation of tobacco smoking frequency among girls at the age of 15-18 years in Poland was performed. Moreover, the general trend referring to smoking among this group was analyzed. In this article the results were used form such a research projects as: HBSC (Heath Behavior in School-aged Children. A WHO Cross-national Collaborative Study); ESPAD (The European School Survey Project on Alcohol and Other Drugs) and "Mokotowskie Research", leaded by Institute of Psychiatry and Neurology. PMID- 20301911 TI - [Analysis of the phenomenon and the knowledge of smoking cigarettes among pupils and students]. AB - The aim of presented study was to comparison analysis the attitude related to smoking habit among pupils and students. Data was collected through questionnaire which was filled individually and independently by each respondent and additionally anonymity was guaranteed. Research covered group of 135 elementary school pupils, 131--high school, 106--grammar school and 294 students. The questionnaire covered such topics as: beginning and reasons for cigarettes smoking, the environment of surveyed and knowledge about diseases connected with smoking, trials to break smoking cigarettes. PMID- 20301912 TI - [Does elitism of school influence the smoking-related health behaviour among grammar school students?]. AB - The aim of the study was connected with smoking health behaviour estimation among public (SZP) and nonpublic (SZN) grammar school students. The analysis of 156 anonymous questionnaires was made. Questionnaires contained questions of parents' education, material situation of family, physical education, social relations with family and peers and positive or negative perception of smoking. In total trial we observed a strong positive correlation between style of smoking or number of smoked cigarettes and positive perception of smoking (r = 0.62 or r = 0.36 respectively). The latter correlated significantly with family presence of smoking (r = 0.18). Percentages of smoking students of SZP and SZN differed and amounted 22% and 18% respectively. Within I/II SZP classes the smoking depended on material position of family (r = 0.28) and positive perception of smoking (r = 0.68). Among students of III SZP classes the dependence on material situation was stronger (r = 0.49), while students of III SZN classes became to perceive smoking more positive (r = 0.82). Social relations of students of I/II SZN classes were inversely proportional to prevalence of smoking in their families. Smoking students of III SZN classes worked out much more variously in comparison with pupils of SZP. The main motivation of smoking within school students was the positive perception of smoking. The differences of smoking prevalence within both types of school probably formed in the families and observed in I/II classes pupils, vanished during the time of III class of studying. Elitism of school do not protect the student from smoking: during the time of III SZN class the smoking receives clearly positive appearance and became established. Probably existing antinicotinic school programs should much more decidedly deliver the negative appearance of health effects of smoking. PMID- 20301913 TI - [The prevalence of tobacco smoking and psychoactive substances use among teenagers from the secondary school--pilot study]. AB - The main of the study was to describe psychoactive substances abuse among teenagers from secondary school and recognition the reasons of tobacco smoking, alcohol drinking and drugs taking. Tobacco smoking was declared by 24% pupils. The main reasons of tobacco smoking, in pupil's opinion, were: addicted influences of nicotine and relaxing effects of smoking. According of the results of the study 16% pupils drank alcohol, on average one teenager of the ninth had or have contact with the drugs. The most famous drugs were: marijuana (66.7%) and amphetamine (33.3%). PMID- 20301914 TI - Popularizing smoking among academic youth during the first years of studies. AB - For several years there have been systematic organization and educational activities carried out in many countries, also in Poland, aimed at large groups of people in order to limit the frequency of smoking. Living in environment free from tobacco smoke is a condition of maintaining good health of an individual and human population. The results of research show that it is very difficult to free oneself from smoking. Therefore, preventive actions among high school and academic youth must be particularly intensified. Health behaviour of post graduates of medical departments who will take up work in health centers in the future will be particularly under scrutiny, and there will be many followers among patients, too. The aim of this work was to establish participation of the smoking people among the first year students, during the first two months of 2008. In March 2008 all of the students of the first year of stationary and non stationary divisions of the Department of Health Science at the Medical University of Lodz took part in the research, using an auditory survey. In total, there were 512 people on students lists. 479 of them took part in the research (93.5%). Among the 479 respondents, 34.2% (164) of the tested admitted to smoking and 65.8% (315 people) answered that in January and February 2008 they did not smoke a single cigarette. Among 308 stationary female and male students, those who smoked (88 people) made up for 28.6%, whereas among the 171 of the non stationary tested students, those who smoked made up for 44.4% (76 people). In the group of smokers 53.7% (88 people) were the stationary students and 46.3% (76 people) were the non-stationary ones. Participation of smoking students in January and February 2008 among all of the students at the Department of Health Science was very high--tobacco smoke was inhaled by every third student. PMID- 20301915 TI - [Spreading of smoking habit among students of the Public Medical Higher Professional School in Opole in 2006-2009]. AB - Smoking is the most widespread addiction and for years is a basic addiction hazard among youngsters. The beginning of nicotine addiction is occult, during time runs as habit and biological nicotine addiction. The health consequences are seen after time. Children have their first contact with cigarettes in their own families and the problem of smoking is the consequence of following adults' example. The risk of smoking addiction rises because of negative influence of background and because of the need of being approved among men of the same age. The objective of the study was the analysis of spreading of smoking among students of PMWSZ in Opole during years 2006-2009.688 students of nursery and obstetrics faculty were investigated. Among them 175 (25.4%) were smokers and 513 (74.6%) were non-smokers. More than half of smokers (61.2%) started smoking in secondary grammar school. 110 (62.9%) of them tried to overcome their addiction. These failed attempts confirm the necessity of multi-aspect anti-nicotine help given by health professionals: doctors, psychologists, addiction therapeutics and pedagogues. PMID- 20301916 TI - [Prevalence of tobacco smoking university students and health locus of control]. AB - Global spread of diseases of civilization, such as cardiovascular disease, metabolic diseases, cancers, caused, that individual or group healthy behaviours, have become, for practitioners and researches, a basic area of interest. Healthy behaviours are the effect of shaped attitude against health, and particular against a sense of responsibility for owns health and co-responsibility for others health. Health Locus of Control theory indicates, that there exist relations between owns health locus of control and providing pro-health activities, for example reduce tobacco smoking. The aim of the study was the assessment of relation between prevalence of tobacco smoking among university students and health locus of control. The study was carried out among 457 university students from Podkarpackie Region- University of Rzeszow PWSZ Krosno and PWSZ Sanok. The survey was conducted by means of diagnostic survey with the use of questionnaire and Multidimensional Health Locus of Control Scale Form B- MHCL-B. The Spearman's rank correlation coefficient and chi-square test were used in statistic analyzes. The study proved that the majority of students has never smoked and does not smoke. Place of residence turned out to be a differentiation factor of tobacco smoking, and there were more smokers among students living in cities. There were observed no characteristic differences in the group of smokers and non-smokers and health locus of control. Internal control, in the opinion of studied group, was recognized to be the most important factor, more less role was attributed to the impact of others and a chance. Faculty of study turned out to different the assessment of importance of internal control and a chance for health state. Internal control was the least emphasized by nursing students, and a chance by obstetrics students. PMID- 20301917 TI - [Competence of pharmacy students of the Jagiellonian University Medical College, Department of Pharmacy in Cracow in the problem of tobacco addiction]. AB - Over 1.2 billion people in the world are addicted to tobacco products. Tobacco smoke contributes to increased risk cardiovascular diseases, respiratory diseases and development of cancers. A survey carried out in lines of medical students was assessed prevalence of smoking and attitudes toward the problem of smoking. This research has never been carried out with departments of pharmaceutical students. The aim of this work was to assess the level of knowledge of students Pharmaceutical Faculty of the Jagiellonian University in Krakow addiction from smoking cigarettes, the harmfulness of smoking, knowledge of preparations used in the course of emergence from addiction and move topic dependence on tobacco smoking during the study. Carried a voluntary and anonymous survey, allow for verify and compare the knowledge of issues related to smoking, as well as some idea of how many students smoke cigarettes. The study was performed in the group of 485 students, including 378 from the Pharmaceutical Faculty and 107 from Medical Laboratory Department from all years. As is clear from the survey conducted students from higher years to cope better with questions about carcinogens, diseases caused by tobacco smoking and have bigger knowledge about antinicotine preparations. Among students from IV and V years is also the most people claiming that they can provide anti-smoking advice. It was found the largest proportion of smoking students on the IV and V year. The greatest knowledge of tobacco dependence Faculty of Pharmacy students acquired in class with toxicology, physiology and biology. Universities have a huge scope for action in conducting antinicotine programs. PMID- 20301918 TI - [Level of tobacco smoking amongst 6th year students of Wroclaw Medical University]. AB - Prevention of tobacco smoking amongst youths and young adult could limit deaths because of illness tobacco related to 2050. The assessment of the level of smoking was the aim of examinations amongst medical students. An anonymous questionnaire containing questions on the subject of tobacco smoking was carried amongst 6th year students of the Medical Department of Wroclaw Medical University in the academic year 2008/2009. Two hundreds then students took part in the study. 62% of examined came from the provincial capital, the 11.4% from the town with the population above 100 hundred of inhabitants, 22.4% of towns with the population below 100 hundred of inhabitants and 3.8% of students--from country centers. 14.8 % respondents admitted to smoking cigarettes, 75.2% were non smoking persons, 10% were smokers but ceased smoking cigarettes in the sequence of a few last years. Amongst smokers--the most (59% of students and 71% of students) is smoking to 5 cigarettes per day. The most students (56% of women and 60% of men) began smoking in the secondary school. In studied group 67.6% (142) examined is claiming that the anti-tobacco advice should give family doctors, and 43% thinks that a patient which isn't able to cease the smoking in spite of strong motivation should be seen by a family doctor. The percentage of smokers amongst medical students didn't take turns in the sequence of two last years, however amongst smokers--biggest percentage is smoking to 5 cigarettes per day. The students most often begin smoking in the secondary school. The straight majority of the medical students is paying attention, that family doctors should take up giving the anti-tobacco advice and helping patients which isn't able to cease the smoking in spite of strong motivation. The ones smoking the small number of cigarettes and which began smoking in the secondary school are predominating amongst smokers. Overbalancing percentage of examined is located anti-tobacco therapy into competence of a family doctor. PMID- 20301919 TI - [Comparison the phenomenon of smoking cigarettes among cosmetology students and personnel beauty salon from Podlaskie county]. AB - The aim of the study was to learn the attitude towards tobacco smoking of cosmetology students and personnel of beauty salon. This study was one of the results of the Preventive Medicine Program implemented at the University of Cosmetology and Health Care in Bialystok. Data was collected through questionnaire which was filled individually and independently by each respondent and additionally anonymity was guaranteed. Research covered group of 98 students and 100 women working in beauty salons. PMID- 20301920 TI - [Occurrence of cigarette smoking among pregnant women]. AB - Life-style is defined as any set of human behavioural patterns, either conducive or detrimental to health. It is the most important factor influencing health. Cigarette smoking is emphasised as one of its determinants, as far as behavioural patterns detrimental to health are concerned. The article chiefly focuses on presenting the occurrence of cigarette smoking among pregnant women. The intermediate objectives were to identify the behavioural patterns discussed, concerning the immediate social surroundings of the future mothers. The study was conducted in the Province of Wielkopolska in 2009. It included 105 pregnant women. A diagnostic survey was applied; the tool: a questionnaire. It was established that the majority of the pregnant respondents assessed favourably both their own health and the preparation to their future role as mothers, 60.95% and 68.57%, respectively. All women participating in the study did not smoke, in contrast to their immediate family members, the majority of whose smoked. Pregnancy requires maintaining a proper life-style from a concerned woman: it influences her and her child's well-being. One of the main tasks of public health specialists is to provide young women with information set, concerning health promotion and shaping of desirable attitudes, conducive to health. Education concerning such a life-style should be directed not only at pregnant women but also at their spouses. PMID- 20301921 TI - [Cigarette smoking and alcohol consumption in patients with oral cancer]. AB - The study aim was to analyse the frequency of simultaneous smoking and alcohol consumption in 142 patients with oral cancer and in the control group. A connection between the prevalence of these habits and epidemiological traits of the patients and features of malignant lesions was evaluated. Statistical analysis revealed that simultaneous smoking and alcohol abuse were significantly more frequent in the cases group. A strong influence of these habits on the development of oral squamous cell carcinoma was noted. PMID- 20301922 TI - [Tobacco smoking among hospitalised patients with coronary arterial disease]. AB - The impact of tobacco smoking on the development of cardio-vascular diseases, including coronary arterial disease (CAD) is very well known by now. More than 1/3 of the Polish adult population are affected which roughly corresponds with WHO accepted percentage of smokers world-wide (over 30%, over 15 years of age). Smokers with cardio-vascular problems are, naturally, even more dramatically affected. The article focuses on selected consequences of tobacco smoking among patients with coronary arterial disease. One hundred patients, already diagnosed with CAD, and hospitalised because of it, formed the studied group (71 male, 29 female). A survey questionnaire was employed as a tool, to inquire the subjects on elements of their life-style, encompassing both declared, acquired knowledge on behavioural patterns conducive to health and its implementation in every-day life. The life-style patterns included, for example, proper diet, physical activity and tobacco smoking. The study results showed that 97% of the group were well aware of the negative influence of smoking on their health (the remaining 3% left the question unanswered). None of the respondents was convinced of the alleged positive aspects of tobacco smoking. At the same time, 17% of the subjects with CAD still smoked, 56% ceased smoking, and the remaining 27% never smoked. The study revealed moreover that the very realisation that nicotinism influenced the CAD progress was instrumental in ceasing smoking by the 56% of former tobacco addicts. Tobacco smoking remains an issue among persons with diagnosed coronary arterial disease. A clear discrepancy was noted, between the almost 100% awareness of the habit's harmful consequences and reality of every day life. PMID- 20301923 TI - [Cigarette smoking in selected group of primary hypertension outpatients]. AB - Primary hypertension belongs to the major health risk factors affecting mostly populations in developed countries. One of the risk factors responsible for cardio-vascular diseases morbidity, including primary hypertension is cigarette smoking. The aim of this study was to assess the prevalence of cigarette smoking in a group of 33 primary hypertension outpatients and 29 healthy individuals. If was found that in the past primary hypertension outpatients smoked cigarettes more frequently, in higher quantity per day and for a longer period of time, in comparison with the healthy subjects. Besides, currently over 20% of outpatients declared cigarettes smoking which, may diminish the efficacy of antihypertensive drug therapy. PMID- 20301924 TI - [The occurrence of tobacco smoking and obesity in schizophrenia women]. AB - The aim of this study was to assess the occurrence of tobacco smoking and obesity in 58 schizophrenia women aged 45.1 +/- 9.9 years. 72% of women declared tobacco dependence as well as 14% smoked dependently on mood and 14% didn't smoke. There were statistically significant differences between women whose smoke or not in the case of BMI. The smoking women had significant higher BMI than non-smoking women (27.81 +/- 3.51 vs. 22.35 +/- 4.29, respectively). We didn't observe such comparisons between period smoking women and smoking women as well as non-smoking women. In the case of frequency distribution of schizophrenia women according to BMI we observed significant differences in this parameter. In the little underweight women (BMI below 20, n = 5) 60% didn't smoke. In the group of normal weight women (BMI = 21-25, n = 14) 64% smoked and 22% didn't. In the groups of overweight women (BMI = 26-30, n = 28) and obese women (BMI > 30) most of them were smoked. In the first of those groups 79% were smoking women and only 7% nonsmoking as well as in the second--all of women were smoked. These results show that the tobacco dependence and obesity could strongly correlate in schizophrenia and we need more studies in this case. PMID- 20301925 TI - [Degree of nicotine dependence in the Gastroenterology Ward of Clinical Hospital number 4 in Lublin]. AB - It is common knowledge that smoking badly influences people's health. Amount of toxic chemical substances delivered to the human organism is directly proportional to the number of smoked cigarettes. Tobacco smoking increases the number of ill people and accelerates death. The problem of nicotine addiction has both social and medical aspects. The aim of the work was to assess the tobacco smoking among patients hospitalized in the Gastroenterology Clinic in SPSK 4 in Lublin. We found that smoking prevalence in the investigated group considerably exceeds the average values for Polish population. PMID- 20301926 TI - [Polish nurses' smoking behavior and environmental tobacco smoke exposure]. AB - The aim of the study was to evaluate the nurses' exposure to active and passive smoking. The study population consisted of 299 nurses. Among the study population detailed questionnaire was conducted incusing sociodemographic characteristic, smoking profile and environmental tobacco smoke exposure. About 18% of nurses indicated current tobacco smoking and 25% smoking in the past. Only 13% of the study population declared complete ban of tobacco smoking in their homes and 20% indicated exposure to tobacco smoke in the workplaces. The women were most frequently exposed to inhaling tobacco smoke in bars and pubs (97%), restaurants (65%) and in private cars (64%). PMID- 20301927 TI - [Socio-demographic factors and the prevalence of tobacco smoking in the workplace]. AB - Tobacco smoking constitutes to be the main cause of health risk in Poland and is one of the most harmful elements of human's lifestyle. Workplace was recognized as a major source of tobacco smoke exposure for others. There should be keep in mind, that in present, it is a task of both employers and employees to create and maintain a safe work environment. The aim of the paper is to assess the prevalence of tobacco smoke among employees of one of the biggest works in Podkarpackie Region, with regard to age, gender, education and performed function. The study was carried out between January and March 2008 in the biggest works on Podkarpackie Region, within the programme "Smoke-free workplace". On the first stage of the study the prevalence of tobacco smoking was assessed, and the opinions of employees of 1291 about the problem of tobacco smoking were known. The survey was conducted by means of diagnostic survey with the use of questionnaire. The chi-square test was used in statistic analyzes. It results from the study, that the majority of studied employees never has smoked and do not smoke. The problem of tobacco smoking among studied group in general did not considered women. A large group of studied employees (smokers and non-smokers) indicated, that only occasionally is exposured on passive smoking, or this problem did not consider them at all. It was stated, that there are differences in gender, age, education and tobacco smoking. More than a half of studied men do not smoke, and represents younger and better educated group. A position also differentiated studied employees in the scope of tobacco smoking. People on high managing positions smoked slightly more frequent. PMID- 20301928 TI - [Detection of nicotine dependence in different age groups]. AB - The work discusses the usefulness of different diagnostics tests helpful in nicotine dependence diagnosis in relation to patients age. The Hooked on Nicotine Checklist (HONC) test proved to be the most useful for the group of teenagers whereas for adults the CAGE questionnaire, the Four C test, the Fagerstrom Test for Nicotine Dependence (FTND) and Heaviness of Smoking Index (HIS) gave the best results. In the elderly people age group the limits of FTND and HIS test were pointed out. PMID- 20301929 TI - [Smoking among the unemployed: impact of structural factors on lifestyle]. AB - In times of economic crisis, questions arise about its relationship to the state of public health. One of the responses might be to investigate health behaviors of people who suffer most from the crisis, which is the unemployed. This study focuses on the many links between smoking among the jobless and other aspects of their lifestyle as well as selected social factors. In our research, we used statistical methods and a questionnaire. based survey. The research was conducted in 2007 and it covered 1,068 unemployed persons registered with the District Employment Office in Poznan. The prevalence of smoking among the unemployed is higher than the national average and is associated with their socio-economic status, gender and such lifestyle aspects as the amount of alcohol consumed, the amount of free time, body mass index, the number of meals consumed, the number of persons the unemployed can rely on, and the amount of time devoted to exercise. PMID- 20301930 TI - [Cigarette smoking among the unemployed registered with Poznan District Employment Office]. AB - The aim of this paper was to present the incidence and causes of smoking among those currently unemployed, and to show changes, if any, resulting from their continued joblessness. The analysis was based on the results of 1,068 surveys taken in 2007 among the unemployed registered with the District Employment Office in Poznan. It was found that cigarette smoking among the unemployed remains high and is associated with the respondents' gender, educational background, economic status and duration of unemployment. Severity of smoking increased more often for those unemployed on a short-term basis, with a number of smoked cigarettes per day more likely to decrease for those in medium- and long-term unemployment. Respondents quoted two equivalent reasons for smoking: wanting to have a cigarette and frustration. PMID- 20301931 TI - [Tobacco smoking in small communes of Lodz province]. AB - Tobacco smoking sill remains a dominating, single and variable risk factor of circulatory system diseases (CSD) morbidity and mortality. The population studies conducted over the last years in Poland makes the monitoring of CSD risk factors, including smoking frequency, possible, however mainly in urban populations. The purpose of the study was to determine the tobacco smoking frequency in rural population of Lodz province depending on such demographic-social features as: sex, age, marital status, education level, professional activity and income. The study, which is a part of the Multi-Center Representative Nationwide Health Survey of Population (WOBASZ), included 324 inhabitants of two randomly chosen, small (up to 8.000 inhabitants) communes in Lodz province - Zloczew and Ostrowek. The tobacco smoking frequency (regular and occasional) in the investigated group was 24.7%, among men--34.7%, among women--16.1%. Women who smoke cigarettes were usually aged under 34 whereas men-smokers were most frequently under 55. Regular smokers smoked on average 14.6 +/- 7.23 cigarettes per day (men constitute significantly larger statistical group than women). The average duration of regular smoking was 21.8 +/- 13.01 years. Persons who had never smoked constituted 62.3% of the investigated group (50.0% of men and 73.0% of women). Among the inhabitants of small communes of Lodz province, persons with a low level of education (vocational education) and higher (or incomplete university) education smoked most frequently. In the latter education-level category, only a small group of men smoked (0.15) and as many as ? of women. No statistically characteristic dependence between tobacco smoking and professional activity, education level, marital status or month income was found (although men-smokers were most frequently unemployed and least frequently farmers). PMID- 20301932 TI - [Smoking from the perspective of positive psychology]. AB - Cigarette smoking remains a significant problem on a global scale. Positive psychology is blazing new trails in researching the mutual relation between health and disease, stressing the promotion of positive factors supporting health. The crucial point in this perspective is examining the factors, that assists healthy behaviours. The paper is an introduction to the research on the sense of happiness and emotionality in the currently cigarette addicted, never smokers and past smokers. Studies clearly show that in people who threw smoking level of happiness and awareness of owns emotions are the highest compared to those never smokers and smokers. PMID- 20301933 TI - [The relationship between tobacco smoking and risk behaviour syndrome among 15 year-old adolescents in Poland and other European countries]. AB - In most of studies on the multiple risk behaviour syndrome, tobacco smoking is consider as one of the main components. In this paper smoking was excluded from this syndrome. On the contrary, a set of behaviours that includes: alcohol abuse, cannabis use and aggressive behaviours (bullying, fighting) was described and its association with smoking related behaviours was evaluated. Data were collected from 15-year-old students (N = 50618) from 28 countries participating in Health Behaviour in School-aged Children (HBSC) survey in 2005/06. Representative samples of pupils completed a standardised questionnaire during school hours in each country. Risk Behaviour Syndrome (RBS) was measured on the scale ranged 0-12 points, categorized into 3 levels. We tried to answer the following questions: 1) is early tobacco onset related with the higher risk of being involved in multiple problem behaviours; 2) what is the prevalence of regular tobacco smoking among adolescents reporting multiple problem behaviours; 3) in what extent gender modifies above relationships; 4) are similar patterns observed in Poland and combined international sample. The results have shown, that in Poland 22.6% of boys and 5.0% of girls reported high level of RBS (6 points or more). The prevalence of every day smoking was equal to 14.9% and 10,1%, in boys and girls, respectively. This percentage increased to 38.8% and 61.0% in the group of boys and girls reporting high score on RBS scale. More boys than girls started to smoke at age 13 yrs or earlier (38.6% vs. 27.1%). Adolescents who begun smoking earlier, were more likely to be regular smokers at age 15, and more likely to report multiple risk behaviors. In all countries the influence of early tobacco onset on the RBS is more evident among girls. PMID- 20301935 TI - [Smokers' motivation to quit smoking]. AB - Smoking is a commonly recognized risk factor of civilization diseases. The number of damaging compounds, including carcinogenetic, inhaled by a smoker and exhaled, is directly proportional to a number of smoked cigarettes. Currently 32% of the Polish adult population smoke tobacco (38% males and 26% females), which is a serious social and healthy issue. The aim of study was to recognition opinions about smoking and motivations to quit. Altogether 384 adults participated in the survey. 207 were smokers and 177 people who had quit. Author contrasted two groups of the respondents to find out the differences. For the both groups the most important motivations to smoking cessatiom were healthy reasons independent of sex, age and education. PMID- 20301934 TI - [Knowledge about influence of smoking tobacco on health condition and developing fetus of the patients of women health center in urban and rural areas]. AB - Chemical compounds that are present in tobacco smoke negatively affect the health of everyone, but most of all it damages the organism of the developing and young bodies. Both passive and active smoking is harmful. The level of knowledge in the society concerning smoking increases systematically. However, many people choose to ignore warnings and prohibitions concerning smoking. From the findings it results that 60% of the pregnant women is threatened with inhaling tobacco smoke at work place or at home, and almost every third pregnant woman smokes. The aim of the research was to recognize the knowledge about the influence of smoking tobacco on the developing fetus of the patients of health centers in Lodz and in Opoczno. Between 1st and 15th April 2007, there were studies carried out using an auditory survey among 240 female patients who came for advice at the health center. One health center in Lodz was chosen at random and one in Opoczno. Subsequently, people queuing to the doctor's were asked to fill the survey, until 120 patients completed it. Collected material was then analysed statistically. The questionnaire consisted in total of 28 questions, including 11 concerning patients' knowledge about the influence of smoking tobacco on health. Almost 21% of the questioned was of a mistaken opinion that not everyone can quit smoking. Over 16% of them did not know that smoking may lead to vascular diseases and 2% of women did not see the connection between smoking and respiratory system diseases, 11% of the surveyed did not know that smoking is harmful and over 10% did not know that passive smoking has negative effect on the developing fetus. Defects in knowledge concerning influence of smoking, particularly passive smoking on the frequency of illnesses occurrence and the development of fetus, among some of the respondents, requires the increase of didactic activities of health care workers. PMID- 20301936 TI - [Health behaviors of nicotine addicts]. AB - Nicotine addiction is a huge social problem and at the same time it is one of the most popular and well-known risk factor in many diseases which can be eliminated. The aim of the study was to asses differences in the health behaviours from regard on type the dependence of from nicotine. In the study participated 221 (males and females) persons dependent on nicotine. In this study applied: Inventory of Health Behaviour--IZZ by Juczynski and Fagerstrom Test for Nicotine Dependence. Received results show that health behaviours are practiced more often by women and it is not dependent on the level of their addiction. Among men the type of nicotine addiction differentiates the frequency of applying the healthy behaviours. Pharmacological addicts have fewer tendencies to behave in healthy way. PMID- 20301937 TI - [Pro health of attitudes of elderly persons with regards to addiction of smoking at the present transformation time]. AB - The aim of the research is a subjective health assessment by the old and their level of health awareness about tobacco smoking. The research was carried out by means of the FACIT survey (abridged version) done to examine 80 elderly people (45 women, 36 men) The FACIT scale was employed to evaluate health condition in the area of physical efficiency, psychosocial functions and patients' general opinions about their health. Most of the examined were people with low health self-assessment and low level of knowledge about tobacco smoking. The insufficient health awareness level of the examined elderly people indicated a necessity of implementation of education programmes and easy access to health promotion institutions. PMID- 20301938 TI - [The police officers' knowledge about the health consequences of smoking tobacco]. AB - Smoking tobacco by the public service workers is a serious health and social problem as its consequences may restrict their efficiency. The aim of the test was assessing police officers' knowledge about smoking affecting health condition. The research tool was a questionnaire that included questions about knowledge on health consequences of smoking. The research included 102 police officers of District Police Headquarters in Tomaszow Mazowiecki. The average age was 36.0 +/- 7.36 years. The frequency of smoking in the group was 66.7%, the regular smokers constituted 56.9%. The level of knowledge among smokers and non smokers was diverse. The smokers knew less than the nonsmokers, especially in the area of the influence of smoking on cardiovascular system and physical efficiency. The police officers knew about the influence of smoking on sense organs the least. It is recommended to implement systematic educational actions to increase the knowledge level about the health consequences of smoking tobacco. PMID- 20301939 TI - [Knowledge and behaviour concerning smoking tobacco among police officers]. AB - Job of a policeman belongs to the group of jobs with highest factor of psychological load. Working under high stress results in police officers reaching out for a cigarette, regardless of their knowledge about how harmful it is, believing--quite wrongly--that this will lower the stress level. The aim of the research was to determine the behaviour of policemen concerning smoking tobacco and evaluating their knowledge about its influence on health. In Poland in March and April 2008, there was research carried out using an auditory survey among 315 police officers of City Police Station in a city of almost 80 thousand people. The survey was completed by 102 people, which makes up for 32.4% of the total number of employed. Among the respondents there were 86 men (84.3%) and 16 women (15.7%). Age average of the surveyed was 37. The highest number, 76 people (74.5%) were graduates of high schools. Majority, 50 people (56.9%) had been in police service for over 15 years. Answering the questions included in the survey, concerning smoking cigarettes during two months prior to the questionnaire, 40 people (39.2%) admitted to smoking. This number included 28 people (27.4% of the total number of the studied cases) who claimed they had smoked every day, seven people (6.9%) responded they smoked almost every day and 5 people (4.9%) smoked from time to time. In the group of 30 smoked men, majority, that is 16 people answered they had smoked everywhere they wished to, disregarding signs prohibiting smoking. Evaluating the influence of smoking on health, 88 people (86.3%) claimed it was very harmful. Vast majority of the studied cases, that is 78 people (76.5%) thought their knowledge about negative effects of smoking was high enough, but almost half of the studied cases, that is 48 people (47.1%) claimed they had never heard about actions or antinicotine campaigns in Poland. Popularizing smoking among police officers who agreed to take part grounds to claim that police officers who did not agree to take part in completing the survey also smoked cigarettes. Majority of police officers who smoked, inhaled tobacco smoke disregarding their knowledge about the damaging effect of smoking. PMID- 20301940 TI - [The opinions of employees about smoking in the workplace]. AB - Smoking is now a serious social problem in Poland and abroad. Unfortunately, adverse effects also affect the businesses in which the crews smoke tobacco. For several years a wide-ranging measures aimed at reducing the population of smoking employees can be observed, unfortunately their results are significantly below expectations. What must be noted is that the effectiveness of these projects to a large extent is determined by the opinion of the smoking part of the crew about the problem of smoking in the workplace. The aim of this work was to analyze the opinions of employees about smoking in the workplace. The selection of study group was expedient. The people tested were permanent employees of a large plant in Rzeszow. The research materials were the answers to the questions given to an anonymous survey. The survey contained 21 questions about their opinions to smokers and 17 questions about their opinions to non-smokers. The perception of risks arising from the smoking of tobacco by smokers and non-smokers was asked for, and their expectations towards the company. They were asked also the willingness to join special programs helping in quitting the addiction of smoking. The individuals who smoke at least one cigarette a day were recognized as daily smokers of tobacco (as defined by WHO). Those who used to smoke every day in the past or occasionally were considered as ex-smokers. (less than one cigarette per day). 4200 surveys were distributed in the plant. The filled - in forms with replies were received from 1412 workers, representing 33.6% of questionnaires distributed. All the surveys were put in order and checked on its merits. 1291 were classified as correct, what represented 30.7% of questionnaires distributed. The latest version of the program Statistica 8.0 was used for the statistical calculations. Test results show that 14.9% of employees smoke tobacco, and every third smoker is worried about the consequences of smoking. As far as opinions on the presence of smoking in the workplace are concerned, most workers believe (94.3%) that the employer should do everything to protect the non smokers from having to inhale tobacco smoke. Only one in ten believes (11.4%) that talking about the harmfulness of smoking is the attack on the freedom of smokers, and argues that there is a lot of exaggeration in speaking about the harmfulness of smoking. As for the negative effects of smoking the most frequently mentioned are health consequences (36.6%). In a population of smokers 17.9% want to quit smoking very much and one in ten do not consider such possibility. What is comforting, however, is that 48.9% of respondents expressed opinions about joining the pro-health program which goal is to help in quitting smoking. The study shows that the vast majority of staff believes that the employer should protect the non-smokers from inhaling tobacco smoke and help the smoking employees in quitting smoking. More than half of all workers considered that the employer should help the employees to quit smoking addiction. Smokers worry about the health consequences resulting from tobacco smoking. Almost half of respondents expressed their willingness to join a program helping in releasing from the addiction of smoking, but a large group of smokers has not shown such an interest. Age and level of education do not affect the motivation to release from the addiction of smoking among smoking employees. PMID- 20301941 TI - [Opinions about smoking bans and e-cigarettes among inhabitants of Poznan--the results of a pilot study]. AB - The aim of the pilot study was to assess the opinions about smoking bans and e cigarettes among inhabitants of Poznan. In this research we used inquiry-sheet public opinion tool verifying acquaintance of problem. Opinions in that survey were different among men and women. Most women declared support for smoke-free policies. The highest level of support was for smoke-free public transport. Majority of respondents believed that polish smokers do not respect smoke-free regulations. E-cigarettes have not a big chance to be popular in Poland. PMID- 20301942 TI - [Opinions of the participants of 'Quit and Win' competition concerning prizes motivating to refrain from smoking]. AB - Big antinicotine campaigns both in Poland and worldwide, are finished with a competition with prizes of different value. Psychologists say that a prize significantly motivates a person to certain kinds of behaviour. During educational activities carried out in the time of campaign, it is recommended to use techniques of psychological interaction that would release motives most beneficial to health. The aim of the work was to recognize frequency of being influenced mostly by the possibility of winning a prize before making a decision about quitting smoking and joining the competition, and learning the opinions of prize laureates concerning efficiency of 'Quit and Win' competitions. Empirical material comes from two sources. The first one is the selected fragments of a survey study carried out at Social and Preventive Medicine Department among 1700 participants of 'Quit and Win' competition that finished the 2nd International Antinicotine Campaign in Poland. The correctly filled survey was sent by 1285 people, that is 75.6%. The second source is a fragment of a survey study carried out in 2003 among 54 laureates of 'Quit and Win' competition in Poland. The completed survey was sent by majority of the laureates, that is 34 people (f = 0.63). Possibility of winning a prize as the most important reason for taking up the attempt to stop smoking and joining the competition was pointed to by 56 respondents (4.4%), whereas the remaining people chose other reasons as the most important ones. In the group of 34 respondents who were the laureates of competitions, majority, that is 22 people (f = 0.65) claimed the competition with prizes as a very effective method of reducing smoking. Half of the surveyed (17 people) claimed the possibility of winning a few prizes of high value would be more motivating than winning one of many prizes of smaller value. As the least attractive, prize gifts were pointed to. A prize in the form of a trip or holiday was considered very popular, as much as money prize. A chance to win a prize was considered the most important motive in undertaking the attempt to refrain from smoking by a small number of participants of 'Quit and Win' competition. In the opinion of majority of the respondents who were laureates of competitions as chosen at random, competitions with prizes organized at the end of campaigns are an effective method of antinicotine prevention. PMID- 20301943 TI - [The students of Public Higher Medical Professional School in Opole spreading anti-tobacco advice]. AB - Smoking tobacco in our society is the primary risk factor in the emergence of many diseases, including cardiovascular and cancer, elevating the risk of mortality before 65 years of age. Very important is the fact that this is a removable, which can be completely eliminated. The smoker health could be in better conditions and also other people from his environment. A man who is messed up is the sick man who, while having the motivation to stop smoking, need a comprehensive and specialized medical treatment. Respondents nursing and midwifery students in Opole PMWSZ most important in providing advice to patients students choose family doctors (34.1%) and internists (17.9%). According to the respondents, patients who, despite a strong motivation to stop smoking can not, should find help in specialized anti-tobacco clinic (27.8%), substance abuse treatment clinic (16.5%), and psychological counseling (11.4%). Half of the surveyed students (51.35%) declared the ability to advice patients, while only 18.7% of respondents correctly answered the question what is the minimum intervention of tobacco control, 56% of respondents claimed that it is information to the patient of the consequences of smoking. Important in reducing the health effects of smoking is to prepare health workers to diagnose the problem of addiction and comprehensive professional treatment. PMID- 20301944 TI - [Practical anti-tobacco intervention in education ability of undergraduates of medical faculty]. AB - Minimal anti-tobacco intervention (MIA) is an efficient and inexpensive method of smoking cessation intervention. The ability for practical use of MIA could be acquired by a majority of physicians-practitioners in Poland and other European Union countries. The objective of the work was to establish a practical knowledge in the scope of anti-tobacco strategies of senior students of the Medical Faculty of the Medical University of Bialystok after six-year education. We also assessed the prevalence of tobacco smoking among students of Medical Faculty. The percentage of tobacco smokers between the last course students of Medical Faculty average at 15% of women and 29% of men. Only 3 of all woman and half of men think they could effectively help in smoking cessation, but most of the assessed students have not acquired sufficient knowledge for an anti-tobacco intervention as well as they don't know practical tools like Fagerstom Test for Nicotine Dependence or Schneider's Smoker Complaint Scale. PMID- 20301945 TI - [Acting in the framework of the nicotine addiction prevention--the level of knowledge amongst 6th year students of Wroclaw Medical University]. AB - It was stated explicitly that smoking was increasing the risk of the death about 25-40% because of cardiovascular diseases, about 30-40% because of malignant tumors and is causing about 70% of deaths from illness of the respiratory system (no cancerous). It was also proved that basic means increasing the effectiveness of taken attempts to limit the smoking were useful and easy to apply by every doctor independently of the medical specialty. An anonymous questionnaire containing questions on the subject of the realization of problems connected with the tobacco addiction in the route of medical studies was carried amongst 6th year students of the Medical Department of Wroclaw Medical University in the academic year 2008/2009. 210 students took part in the study. 62% of examined came from the provincial capital, the 11.4% from the town with the population above 100 hundred of inhabitants, 22.4% of towns with the population below 100 hundred of inhabitants and 3.8% of students--from country centers. Only 78% of students is claiming that problems concerning nicotinism were being brought up on the university. 56.7% of examined is judging that he is able to give an anti smoking advice to a patient. The correct answer in the question about the Fagerstroma test and describing physical addiction gave 47% of students, only 39.5% examined--in the question about the assessment of motivation test (the Schneider scale), and 37.2% of students responded to the question what is consists in minimum anti-tobacco intervention. An insufficient frequency of bringing up the problem of smoking on medical studies is visible harmfulness, a consequence is a lowering knowledge amongst students. Little over 3 of students is confirming students that problems concerning the nicotinism were being brought up during studies (mainly during classes in the field of internal medicine), however every sixth of examined students is declaring the knowledge in the case of the patient addicted to the nicotine and every fourth has the knowledge. The preparing graduates of the Medical Faculty for the participation in realization of basic schedules of the promotion of the health and the diseases prevention is developing unusually pessimistically towards above data, the fight against the nicotine addiction is filling one of the essential positions, independently on the medical specialty. PMID- 20301946 TI - Comparison assessment methods of smoking consequences use in primary care. AB - Cigarette smoking is an independent factor influences on development of smoke related diseases (for example COPD, emphysema). The aim of the study was to check correlation between the changes in respiratory tract and use additional tests such as: a spirometric test, a chest radiogram and measurement of exhaled carbon monoxide among subjects. In the study took part 398 people: 182 active smokers, 145 ex-smokers and 71 never smokers. Average age of participants was 49.3 +/- 14.7 years, and number of years smoked cigarettes was 28 among men and 22 among women (p < 0.001). COPD has been diagnosed at 110 women (36-32.7% active smokers, 44-40% never smokers and 30-27.3% former smokers) and at 108 men (53-40.8% active smokers, 52-23.9% never smokers and 77-35.3% former smokers). Emphysema has been diagnosed at 22 women (11-50% active smokers, 3-13.6% never smokers, 8-36.4% former smokers) and at 54 men (23-42.6% active smokers, 1-1.9% never smokers, 30 55.6% former smokers). The measurement of carbon monoxide in exhaled air was noted at 122 active smokers, 2 never smokers and 31 former smokers. In comparison to the chest radiogram, the spirometric test (COPD and emphysema) with the level of CO exhaled by subjects showed strong dependence for emphysema ( = 8.655; p < 0.004; C = 0.207) and for COPD ( = 10.522; p < 0.002; C = 0.228). The same statistically significant correlation showed results among active smokers for emphysema (= 6.919; p = 0.008528; C = 0.272) and for COPD ( = 43.512; p < 0.001; C = 0.633). The research showed that there are strong dependence between gender and tobacco smoking, and also correlation between respiratory tests used in this paper and changes which appeared as results of tobacco smoking. PMID- 20301947 TI - [Effectiveness of smoking cessation in group-based behavioral treatment in association to health status and motivation of participants--own research findings]. AB - The efficacy and cost-effectiveness of behavioral treatments compare favorably with the pharmacotherapies and community-based interventions. Group-based behavioral programs have been scientifically proven as the effective smoking cessation intervention. Aim of the study was identifying predictors of the efficacy of smoking cessation in health factors: health status and motivation and doctor's advice. Program is a multicomponent group-based behavioral intervention with the elements recommended by the US Public Health Service as the most effective. 517 smokers were included into the program in the outpatient clinic setting in years 2001-2007. A point prevalence abstinence (PPA) was estimated by self-reported smoking cessation. Three homogeneous groups of patients according to their status health were established: participants with tobacco-related diseases n = 182, with psychiatric disorders n = 101 and healthy ones n = 150. 59.6% of participants stopped smoking during four-week program. Program was effective in smoking cessation both for sick and healthy participants. Motivational factors, among others health motivation did not distinguish for whole population as well as for participants with tobacco-related diseases. Lack of doctor's advice increased efficacy of smoking cessation both for the whole population and for group with tobacco-related diseases. Nor health status and motivation neither doctor's advice were predictors of behavioral group-based treatment for tobacco smokers. PMID- 20301948 TI - [Assessment of the effectiveness of pharmacists' activities in treatment of tobacco-addicted patients in the context of pharmacists' counselling in Cracow's pharmacies]. AB - Tobacco-related diseases killed 100 millions people in 20th century and unless urgent action is taken, it is predicted that 1 billion people in total will be killed by smoking in this century. Pharmacists as health-care professionals should support the healthy lifestyle campaign and motivate smokers to quit smoking especially as they have the theoretical basis for such counselling. The aims of the study were: 1. to evaluate the readiness of pharmacists employed in public pharmacies to manage patients who would like to stop smoking; 2. to assess the pharmacists' current knowledge of the harmfulness of smoking and methods of treatment of this addiction. The pharmacists were interviewed for readiness to help addicted people and for knowledge of health promotion problems. A study was carried out do determine pharmacists counselling skills. Investigator (monitor) visited pharmacies passing him(her)self off as a smoker who would like to quit smoking and enquired about methods of the addiction cessation. Next the investigator filled in questionnaires according to the pharmacists' answers. Sixty pharmacists were interviewed. The results showed that pharmacists were willing to help tobacco-addicted patients and although they strongly recommended smoking cessation, their knowledge of methods of tobacco-addiction treatment was restricted. The strongest interest and most extensive knowledge of smoking cessation problems was observed in pharmacists ranging in age from 30 to 50 whereas pharmacists over 50 showed the worst results. The reason of this result was due to imperfect factual knowledge and unawareness of the value of pharmaceutical care in the oldest group of pharmacists. Insufficient education of pharmacists may influence the effectiveness of counseling. PMID- 20301949 TI - [Evaluation of nurses' knowledge about heath effects of active and passive smoking and their attitude towards providing smoking cessation activities]. AB - The aim of the study was to evaluate the nurses' knowledge about health effects of active and passive smoking and their attitude towards providing smoking cessation activities. The study population consisted of 299 nurses. About 57% of the women thought that some kind of cigarettes can be less dangerous than other. Almost all of the nurses indicated that tobacco smoking may lead to addiction. Unfortunately only 67% of study population thought that sidestream smoke contains substances dangerous for health. All nurses indicated that tobacco smoking causes lung cancer and 77% of them that it can cause cardio-vascular diseases and only 26% that it increases the risk of bladder cancer. Almost all women indicated that environmental tobacco smoke exposure is dangerous for pregnant women and the faetus. The nurses were educated about health effects of active and passive smoking but they have limited knowledge about the methods used in antismoking counseling. PMID- 20301950 TI - [Smoke-free environment--nurse attitudes towards smoke-free regulations]. AB - The aim of the study was to analyze the nurse attitudes towards smoke-free regulations in public places. The study population consisted of 299 nurses. Among the study population questionnaire was conducted including socio-demographic characteristic, smoking and ETS profile, knowledge about health effects of smoking and abilities for conduction of antismoking counseling. Detail information was collected about nurse opinion on smoke-free public places such as offices, other workplaces, health and educational buildings, restaurants and bars. About 18% of study participants declared current tobacco smoking and 25% were former smokers. Almost all participating in the study women (85%-98%) are in favor of smoking ban in offices, health and educational buildings. 75% supported smoking ban in workplaces but 15% of them were somewhat opposed. Most of the nurses were in favor of smoke-free restaurants (64%) but they were less likely to support smoke-free bars, pubs and clubs (45%). Unfortunately 63% of interview women do not accept smoking ban in private cars. The percentage of women who support total ban of smoking in the presence of pregnant women was 93% and in the presence of children 79%. It is important to conduct educational and informational activities to increase public awareness on health consequences of active and passive smoking and the ways of elimination of such exposures. PMID- 20301951 TI - [Tobacco and health in the activity of the State Sanitary Inspectorate]. AB - This paper presents the activity of the Department of the Health Education and Health Promotion in the Sanitary Inspectorate in area of nicotinism prevention, undertaking during the implementation of the National Program of the Reducing the Health Effects of the Smoking in Poland. The local sections of the health education and health promotion on Mazovia use different forms of activity to encourage quitting smoking: education in schools, working places' monitoring, distribution of the educational leaflets and flyers, public actions for local communities on smoking prevention, etc. Cooperation with a lot of the governmental and non-governmental institutions guarantees the high quality of the health education's activities in this field. PMID- 20301952 TI - Developing of LC/MS method with microwave assisted extraction for determination of methadone and it major metabolite (EDDP) in the blood of patients of methadone maintenance treatment. AB - Opium derivatives as the addictive substances cause many medical and social problems. In treatment of opiates addiction except psychotherapy a long time pharmacotherapy with methadone or buprenorphine are apply. In a recent study both moderate- and high-dose methadone treatment resulted in reductions in illicit opioid use. The aim of the study was develop fast high sensitive liquid chromatography coupled with mass spectrometry for determination of methadone and EDDP after microwave assisted extraction. Developed method for methadone and EDDP determination were linear over the range 5 to 1000 ng/ml for methadone and its metabolite. The method exhibit a good intra and inter day precision, the microwave assisted extraction was also satisfactory with recovery superior to 80%. The mean concentration of methadone in plasma of patients receiving 40 mg of drug per day was 194 ng/ml but in second group (receiving 90 mg of methadone/day) 263 ng/ml. The ratio of the doses was 2.25 but for methadone concentration only 1.36. The much higher ratio (3.25) of concentrations was noticed for EDDP. This observation can support opinion other authoress about polymorphism of methadone pharmacokinetics and pharmacodynamics. PMID- 20301953 TI - [Acute dextromethorphan poisoning based on the records of the Department of Toxicology and Internal Diseases in Poznan]. AB - The recreational usage of dextrometorphan, the popular antitussive medicine, has become alarming in Poland. The euphoric and hallucinogenic activity of this drug manifests after high doses, usually ranging from 225 to 1500 mg that may lead to acute poisoning. Currently, dextrometh-orphan is considered as addictive substance. In this article we describe the symptoms of acute dextrometorphan poisoning that have been observed in 11 patients, aged between 16 and 31 years that have been treated in the Department of Toxicology and Internal Diseases Raszeja Hospital in Poznan. In the course of intoxication the most frequent symptom was balance disturbation (12.50%), impaired motoric coordination (11.36%), confusion (11.36%) and papillary dilation (11.36%). Agitation (9.09%), tachycardia (7.95%), hallucinations (6.82%), disartria (5.68%) and hypertension (4.55%) were less common. The doses of dextromethorphan ranged from 4.28 to 16.67 mg/kg. All the patients were treated symptomatically. They recovered without sequelae and were discharged after 1-3 days of hospitalization. PMID- 20301954 TI - [Confounding variables in observational studies and their influence on obtained results]. AB - In estimating the influence of one variable on another one we must ensure that observed effect is not caused by factors other than these under investigation. These last, called confounders of analyzed variables, influencing simultaneously both analyzed quantities may generate spurious non existing in reality relationships or change direction of these really existing. PMID- 20301955 TI - [Speed drugs]. AB - Until recently "speed drugs" have not awake higher social emotions. Usually they associate with Red Bull, allowed driving long time, and workaholic from modern enterprise to regenerate before next task. Currently on the base of new regulation on the list of controlled substances benzylpyperazine, its related compounds and 17 plants products were added. The article discussed the sources and biological action of these psychoactive substances, which are illegal in Poland. PMID- 20301956 TI - [Cigarette and coffee--pharmacokinetics interaction between nicotine and caffeine]. AB - Coffee drinking and tobacco smoking stand nicotine and caffeine the number one licit psychoactive substances. Many people inseparably combine a cup of coffee with cigarette. The two most important compounds in these products, nicotine and caffeine can influence on there concentration and pharmacodynamics activity in the body. The changes of the level of these compounds can be caused by changes of the pharmacokinetics on the way of enzyme induction by other chemical individuals content in the coffee and tobacco smoke. PMID- 20301957 TI - [Exposition of pregnant women and their children on toxic effect of lead from tobacco smoke]. AB - Presented work is a review of scientific literature regarding mechanisms of adverse effect of lead exposure on pregnancy and child development. The authors discuss lead metabolism in human body and also determine the mechanism of toxic lead effect with a special emphasis placed on its trans-placental transport and the resulting detrimental effects for the fetus. We also discuss the results of studies indicating a correlation between the lead exposition of pregnant women and developmental deficits in the infant. PMID- 20301958 TI - [Cigarette smoking and cardiovascular disease]. AB - Clinical and experimental studies indicate that either active or passive cigarette smoke exposure promotes vasomotor dysfunction, atherogenesis, and thrombosis in multiple vascular beds. Although the precise mechanisms responsible remain undetermined, free radical-mediated oxidative stress appears to play a central role in cigarette smoking mediated athero-thrombotic diseases. These free radicals could potentially arise directly from cigarette smoke and indirectly from endogenous sources as well. Furthermore, potentiated by multiple prothrombotic and antifibrynolytic effects, intravascular thrombosis is the predominant cause of acute cardiovascular events. Epidemiologic, clinical, and experimental data also suggest that the pathophysiologic effects of cigarette smoke exposure on cardiovascular function may be nonlinear. PMID- 20301959 TI - [Tobacco addiction in pregnant women and parturients--anesthetic considerations]. AB - A global increase in addictions also affects pregnant women. In mothers-to be most frequent is tobacco dependence, despite broad spread of information on negative influence of smoking on the mother and infant. Other substance misuse as ethanol but also illicit drugs may additionally coexist in pregnancy. Smoking cigarettes underlies complications of pregnancy and parturition and babies of smoking mothers present with lower birthweight. As a disorder involving a number of pathologies tobacco dependence in pregnant women and parturients implicates an increased peripoerative risk, especially for respiratory and cardiac complications. Anesthetic management of choice is neuraxial blockades, both for labor analgesia and surgery. On contact with tobacco dependent pregnant and parturient patient an anesthetist should also take an advantage for smoking cessation consulting. PMID- 20301960 TI - Smoking and thyroid disease--review of literature. AB - Smoking has multiple effects on the thyroid gland, which is associated with important clinical implications such as the increased risk and severity of autoimmune thyroid disorders especially Graves disease. The influence of tobacco smoking is mainly associated with pharmacological action of nicotine and also with toxins such as thiocyanate. The present review of the relevant literature concentrates on the effect of smoking on the Graves ophthalmopathy and autoimmune thyroid disorders such as Hashimoto disease. The effect of passive smoking on children and the influence of smoking on foetus are also shown. In contrast, the protective influence of tobacco on the thyroid cancer is also widely noticed. Finally, our study describes observations related to the psychological and legal aspects of smoking. PMID- 20301961 TI - [Influence of natural active compounds on the skin in tobacco smokers]. AB - Tobacco smoking is one of the main factors which negatively influence on the skin, and accelerate the process of skin ageing. Skin damaged by smoking appears grey, slack and dry. Oxidative stress is possible mechanism consistent with negative effects of smoking that activate skin premature wrinkling. This paper presents some of natural active compounds as polyphenols or unsaturated fatty acids which can reduce negative effect of smoking on the skin. PMID- 20301962 TI - [History of cigarette smoking. The effect of tobacco smoking on women's health]. AB - History of cigarette smoking started on XV century, when Columb imported tobacco to Europe. Popular using of tobacco we are indebted Jaen Nicot Villeman, the name of nicotine originate from his surname. Tobacco first was exploited like a drug, however now it is a very harmful stimulant. Cigarette smoking is still an actual problem and increased risk of many diseases. Very toxic components of smoke get inside all the organs and upsetting their activities and proper running of the life processes. It is common knowledge that smoking badly influences women's health. Nicotine makes the negative influence on function of ovaries metabolism of hormones and state of osseous tissue. Maternal smoking during pregnancy is associated with obstetrical and pediatrician complication with fetus, newborn and child. The aim of the article is to summarize the role of tobacco smoking on women's health. PMID- 20301963 TI - [Global Adult Tobacco Survey (GATS)--implementation process in Poland]. AB - In the Framework Convention on Tobacco Control ( FCTC) is stated a need to develop national, regional and global program of control, mechanisms, determinant factors, consequences of using tobacco products and inhaling tobacco smoke. One of crucial elements of global control system of tobacco use--Global Tobacco Surveillance System (GTSS) is Global Adult Tobacco Survey (GATS). Poland is amongst several countries which were invited to conduct GATS. The aim of his work s to describe the objectives, aims, and implementation GATS Project in our country. It will base on current experience of WHO Country Office in Poland. GATS is a representative households survey created to systematically monitor various types usage of tobacco products including smoking but also other forms of usage amongst adults (over 15 years of age). The main objective of GATS is diagnosis of current state and reasons for development of the tobacco epidemic amongst adults Poles. This diagnosis is necessary to determine actions in health and socio- economic policy priorities in order to minimize the usage of tobacco products. Researches in GATS Project are to be completed by the end of 209 and data analysis and final report in 2010. PMID- 20301964 TI - [In vitro cultures of tobacco and their impact on development of plant biotechnology]. AB - Tobacco (Nicotiana tabacum) and related species had played a pioneer role in the development of plant biotechnology. Already in thirties of the XX century, aseptic in vitro cultures were established as one of the first plant tissue in vitro cultures. In the next decade the tobacco cultures served for investigations of organogenesis--formation of advetitiuos shoots and roots--the process important for micropropagation. In 60-ties of the previous century, the totipotency of plant cells, i.e. ability for regeneration of the full plant from single cell, has been unequivocally proved on the basis of experiments with tobacco cell cultures. Moreover, thanks to the tobacco in vitro cultures, the medium for performance of plant in vitro cultures was elaborated in 1962, which is the most frequently used medium till now. Tobacco was the first plant regenerated from a protoplast, as well as the first somatic hybrid and chimera in vitro were derived from tobacco cultures (the 70-ies). Tobacco was also one of the first transgenic plants and for its formation in vitro culture has been necessary to carry out transformation of tissue and regeneration of shoots and roots. Simultaneously preformed cell suspension culture of tobacco exhibited, on one hand, exceptional utility for studies of plant cell biology, and on the other hand, appeared applicable for performing controlled biosynthesis of useful metabolites and biotransformation (bioconversion), that is directed chemical modification of foreign compounds introduced to such culture. Tobacco has played the role of the model plant in investigations of biology and biotechnological applications of plants. PMID- 20301965 TI - [New role for tobacco--production of biopharmaceuticals]. AB - Over one hundred of biopharmaceuticals present on the pharmaceutical market- among them mainly therapeutically peptides and proteins such as hormones, enzymes, interferons, blood factors, monoclonal antibodies, vaccines, growth factors and fusion proteins, are manufactured through recombinant DNA technology in cultures of transgenic bacterial (Escherichia coli), yeast (Saccharomyces cerevisiae) and mammalian cells (CHO, BHK) and rarely insect cells or insects (Bombyx mori). High costs of their manufacturing with simultaneous increased demand for existing and new biopharmaceuticals prompt for the search of cheaper methods of production by using transgenic domestic animals and, in particular, in transgenic crop plants. Among many plant species investigated for ability to produce biopharmaceuticals, such like cereals, legumes, oil plants, vegetables and fruit plants, aquatic plants and mosses, the outstanding features posses two tobacco species--Nicotiana tabacum and Nicotiana benthamiana. Foreign proteins can be expressed in those plants not only in nuclear genome, but also easily in chloroplast genome, through transient transformation and propagation of transgenic plant virus--e.g. tobacco mosaic virus (TMV). Tobacco was shown to be useful to produce various therapeutical proteins, even such complex ones as antibodies including secretory immunoglobulin A (sIgA), with partial humanization of N-glycans. Especially important is possibility of rapid preparation, even within a week, vaccines and monoclonal antibodies for clinical tests or personalized anticancer therapy through transient transformation or infection with transgenic virus. Tobacco with foreign gene may be employed for manufacture in two ways--either in field or green-house cultivation or in the form of in vitro suspension cell culture. Among many biopharmaceuticals expressed in tobacco, several vaccines and antibodies are in advanced stages of development, in clinical evaluations and probably close to application in medicine. PMID- 20301966 TI - Annual report: surveillance of adverse events following immunisation in Australia, 2008. AB - This report summarises Australian passive surveillance data for adverse events following immunisation (AEFI) reported to the Therapeutic Goods Administration (TGA) for 2008, and describes reporting trends over the 9-year period 2000 to 2008. There were 1,542 AEFI records for vaccines administered in 2008. This was an annual AEFI reporting rate of 7.2 per 100,000 population, a 5% decrease compared with 2007. The majority of AEFI reports described non-serious events while 10% (n = 152) were classified as serious. Two deaths temporally associated with immunisation were reported; there was no evidence to suggest a causal association. The most commonly reported reactions were injection site reaction, allergic reaction, fever and headache. AEFI reporting rates in 2008 were 2.7 events per 100,000 administered doses of influenza vaccine for adults aged > or = 18 years, 18.9 per 100,000 administered doses of pneumococcal polysaccharide vaccine for those aged > or = 65 years, and 17.2 per 100,000 administered doses of scheduled vaccines for children aged < 7 years. Reports for infants increased in 2008, mainly related to gastrointestinal system events temporally associated with receipt of rotavirus vaccine in the 1st full year of the rotavirus immunisation program, while there was a substantial decrease in AEFI reports for human papilIoma virus vaccine in adolescents compared with 2007 when the program commenced. Increases in reports in children and adults were also partly attributed to the implementation of enhanced passive surveillance in Victoria. The consistently low reporting rate of serious AEFI highlights the safety of vaccines in Australia and illustrates the value of the national TGA database as a surveillance tool for monitoring AEFIs nationally. PMID- 20301967 TI - Australian Rotavirus Surveillance Program annual report, 2008/2009. AB - The Australian Rotavirus Surveillance Program together with collaborating laboratories Australia-wide, conducts a laboratory based rotavirus surveillance program. This report describes the genotypes of rotavirus strains responsible for the hospitalisation of children with acute gastroenteritis during the period 1 July 2008 to 30 June 2009, the second year of surveillance following introduction of rotavirus vaccine into the National Immunisation Program. Five hundred and ninety-two faecal samples from across Australia were examined for G and P genotype using hemi-nested multiplex reverse transcription-polymerase chain reaction assays. Of the 445 confirmed as rotavirus positive, genotype G2P[4] was the dominant type nationally, representing 50.3%, followed by genotype G1P[8] (22.5%). Genotypes G3P[8], G4P[8] and G9P[8] each represented less than 5% of circulating strains nationally. Uncommon rotavirus genotype combinations, including G1P[4] (n = 6), G4P[4] (n = 2) and single strains of G1P[6] and G3P[6] were identified during this study period. The national dominance of G2P[4] was associated with a large outbreak of severe gastroenteritis in Alice Springs in early 2009. This is the first report to describe G2P[4] as the dominant genotype nationally. Whether vaccine pressure has resulted in emergence of this genotype is not yet known. PMID- 20301969 TI - Outbreak of Salmonella Typhimurium 44 related to egg consumption. AB - ACT Health investigated an outbreak of gastroenteritis associated with a local restaurant in December 2008. The infecting agent was Salmonella serotype Typhimurium phage type 44. A case control study was conducted to identify the source of infection. A total of 22 cases and 9 controls were recruited to take part in the study. Both poached eggs (odds ratio [OR] 42.00) and hollandaise sauce (OR 19.00) had elevated odds ratios that were statistically significant. The major limitation of the study was the small sample size and small number of controls. Despite this, a strong association with illness and consumption of eggs and hollandaise sauce was detected and this was further supported by environmental evidence. The investigation concluded that the cause of the outbreak was putatively contaminated eggs, either on their own or as an ingredient used in hollandaise sauce. The investigation and control measures led to an improvement in hygiene practices at the restaurant and contributed to the voluntary recall of the contaminated batch of eggs from the Australian Capital Territory. The results of the study also build upon other evidence that egg related salmonellosis is now common in Australia and attention to commercial practices at production and processing is overdue. PMID- 20301968 TI - Monitoring the incidence and causes of diseases potentially transmitted by food in Australia: annual report of the OzFoodNet Network, 2008. AB - In 2008, OzFoodNetsites reported 25,260 notifications of 9 diseases or conditions that are commonly transmitted by food. The most frequently notified infections were Campylobacter (15,535 notifications) and Salmonella (8,310 notifications). Public health authorities provided complete serotype and phage type information on 94% of all Salmonella infections in 2008. The most common Salmonella serotype notified in Australia during 2008 was Salmonella Typhimurium, and the most common phage type was S. Typhimurium 135. During 2008, OzFoodNet sites reported 1,545 outbreaks of gastrointestinal illness; affecting 25,555 people and resulting in 691 people being hospitalised. There were 99 deaths during these outbreaks. The majority (83%, 1,276/1,545) of outbreaks were due to person-to-person spread, but 7% (104/1,545) were transmitted by contaminated food. Foodborne outbreaks affected 1,454 persons including 96 hospitalisations. Eleven deaths were reported during these outbreaks. For these foodborne outbreaks, Salmonella was the most common aetiological agent and restaurants were the most common setting where foods were prepared. Twenty of these foodborne outbreaks were related to the consumption of eggs; the majority (n = 18) of these outbreaks were due to various phage types of S. Typhimurium. This report summarises the incidence of disease potentially transmitted by food in Australia and details outbreaks associated with various food vehicles in 2008. These data assist agencies to identify emerging disease, develop food safety policies, and prevent foodborne illness. PMID- 20301970 TI - Outbreaks of Salmonella Typhimurium phage type 197 of multiple genotypes linked to an egg producer. AB - This paper describes outbreaks of Salmonella Typhimurium phage type 197 (STm197) linked to eggs from the farm of a single egg producer. Epidemiological and microbiological investigations (genotyping by multiple locus variable number tandem repeats analysis [MLVA]) identified outbreaks of STm197 with the same or closely-related MLVA profiles in a series of restaurants across Brisbane over 2 months. Environmental health investigations revealed that these restaurants were supplied with eggs from the same egg producer and that cross-contamination may have contributed to the outbreak. Environmental swabs taken from restaurant kitchens and the farm of the egg producer identified a number of salmonellas including STm197, many with MLVA profiles matching or closely related to the human strains from outbreak cases. A case-to-case comparison study showed a significant association between illness with 1 MLVA type and attending a restaurant during the 5 days before onset of illness (odds ratio [OR] 8.1, 95% confidence interval [CI] 1.8, 35.4). MLVA has become a valuable tool for S. Typhimurium surveillance and outbreak investigation. This outbreak further justifies the Commonwealth Government's decision to develop a draft national primary production and processing standard for eggs and egg products to address food safety risks posed by cracked and dirty eggs. PMID- 20301972 TI - Communicable diseases surveillance. PMID- 20301971 TI - OzFoodNet quarterly report, 1 July to 30 September 2009. PMID- 20301973 TI - Being and the death drive: the quality of Green's thinking. PMID- 20301974 TI - Sources and vicissitudes of being in D. W. Winnicott's work. AB - The author questions the reasons for the appearance of the concept of being in Winnicott's work four years before his death. Winnicott illustrated his concept of being by describing a patient in whom he found a complete dissociation of male and female elements. Insisting on the role of the environment and the part played by the mother, Winnicott considered that the pure female element relates to the breast or the mother, in the sense that the baby is becoming the breast. He opined that instinct or drive has nothing to do with this. The present paper discusses this viewpoint at length, comparing Winnicott's and Freud's positions. It is noted that Winnicott introduced his concept of being at a time when he felt threatened by his own mortality. PMID- 20301976 TI - Rethinking pathological mourning: multiple types and therapeutic approaches. AB - Different types of pathological mourning are discussed, with the idea that refining psychoanalytic nosology in this sector can contribute to the enhancement of interventions more suitable for each. Primary fixation to the object--extant before the loss--is differentiated from secondary fixation, which occurs when suffering in the present leads to idealization of an object that is only then felt to be actually lost. The role of narcissism, guilt feelings, and paranoid anxieties in the process of pathological mourning is considered. Clinical material illustrates some of these conditions. PMID- 20301975 TI - Reality testing in place of interpretation: a phase in psychoanalytic work with descendants of Holocaust survivors. AB - Repetition of experience endured by the first generation has frequently been observed in descendants of Holocaust survivors. Such repetitions are associated with an erosion of the ability, in the area of the trauma, to distinguish more or less reliably between external and internal reality. This in turn results from the defensive need, in the affected families, to dissociate from such extreme traumatic experiences. Clinical material is presented to show that, at a certain phase in psychoanalytic work with patients belonging to subsequent generations, interpretive activity may need to be temporarily suspended in order to facilitate reality testing and the recognition of the Shoah as an objective historical fact. PMID- 20301977 TI - The mind as a complex internal object: inner estrangement. AB - The psyche is not a passive container (of emotions, memories, representations, objects, structures, drives, defenses, etc.), and not just an object-seeking organism; it acts on itself as the object of its own scrutiny, which can take many forms. Emphasis on the role of interpersonal object relations has sometimes tended to reduce our working model of the psyche to its internalizations and how these shape personality. This essay uses illustrative clinical vignettes and metapsychological reasoning to explore the mind's relationship to itself and its capacity to act upon itself, arguing that attention to this aspect of clinical material is vital to the psychoanalytic process, fostering what might be described as the growth of internal intersubjectivity. PMID- 20301978 TI - Copies without originals: the psychodynamics of cosmetic surgery. AB - The use of cosmetic surgery and procedures has sharply increased in recent years. This paper outlines an object-relational framework for understanding the unconscious fantasies that may drive the pursuit of body modification and proposes three categories of such fantasies. For some individuals, the pursuit of "beauty" through cosmetic surgery provides a psychic retreat from the reality of dependency as the self retreats into believing that it can create itself (the self-made fantasy). For others, it is a means for creating a felt-to-be ideal self, thereby averting the pain of the loss of an object that would love and desire the self (the perfect-match fantasy). For still others, it may be the only means of expelling an object felt to be alien or polluting that is unconsciously identified with the body (the reclaiming fantasy). PMID- 20301979 TI - Like drives, cultural products exert a "demand on the mind for work": an introduction to two exemplary essays. PMID- 20301980 TI - Computing the unconscious. AB - This essay examines the unconscious as modeled by cognitive science and compares it to the psychoanalytic unconscious. In making this comparison, the author underscores the important but usually overlooked fact that computational psychology and psychoanalytic theory are both varieties of posthumanism. He argues that if posthumanism is to advance a vision for our future that is no longer fixated on a normative image of the human, then its own normative claims about the primacy of Darwinian functioning must be disrupted and undermined through a renewed emphasis on its Freudian heritage. PMID- 20301981 TI - Menu cards in time of famine: on psychoanalysis and politics. AB - The author interrogates the limits of psychoanalytic practice and psychoanalytically inclined political theory. The limits of psychoanalytically inclined political theory are read for what they can tell us about the lasting eclipse of the political, and so, inversely, for what they can tell us about what a viable political culture requires, just as the limits of the political efficacy of psychoanalytic practice are read for what they can tell us about what would be required for its successful realization. PMID- 20301982 TI - Whimsy. PMID- 20301983 TI - A randomized double-blind study comparing the efficacy and safety of orlistat versus placebo in obese patients with mild to moderate hypercholesterolemia. AB - INTRODUCTION: Obesity is a chronic disease and a serious health problem that leads to increased prevalence of diabetes, hypertension, dyslipidemia and gallbladder disease. OBJECTIVE: To evaluate the efficacy of orlistat for weight loss and improved lipid profile compared to placebo in obese patients with hypercholesterolemia, treated over a period of 6 months. METHODOLOGY: In a 6 month, multicenter (10 centers in Portugal), double-blind, parallel, placebo controlled study, 166 patients, aged 18-65 years, body mass index (BMI) > or = 27 kg/m2, LDL cholesterol > 155 mg/dl, were randomized to a reduced calorie diet (600 kcal/day deficit) plus orlistat three times a day or placebo. Exclusion criteria included triglycerides > 400 mg/dl, severe cardiovascular disease, uncontrolled hypertension, type 1 or 2 diabetes under pharmacological treatment, and gastrointestinal or pancreatic disease. RESULTS: The mean difference in weight from baseline was 5.9% (5.6 kg) in the orlistat group vs. 2.3% (2.2 kg) in the placebo group. In the orlistat group 49% of patients achieved 5-10% weight loss and 8.8% achieved > 10%. The orlistat group showed a significant reduction in total and LDL cholesterol, with similar changes for HDL in both treatment groups. The frequency of gastrointestinal adverse events was slightly higher in the orlistat group than in the placebo group, leading to discontinuation in 7 patients. CONCLUSION: Treatment with orlistat plus a reduced calorie diet for 6 months achieved significant reductions in weight, BMI and lipid parameters. PMID- 20301984 TI - Results of the routine use of 4F catheters for diagnostic catheterization in a cath lab. AB - INTRODUCTION: Complications at the site of vascular access are the most common adverse events in cardiac catheterization. The use of small gauge catheters may reduce this risk and allow earlier ambulation, the main disadvantage according to some authors being inferior image quality. The aim of our study was to evaluate the safety and image quality of 4 French diagnostic catheters. METHODS: We performed a retrospective study of 1656 patients who underwent diagnostic cardiac catheterization with 4F catheters via the femoral artery between January 2006 and December 2007, and analyzed the complications during and immediately after the procedure. The quality of the films was assessed in 125 consecutive patients from this group, who were also followed up on average one month after hospital discharge. RESULTS: Cardiac catheterization with 4F catheters was technically possible in all cases. Patients were able to ambulate and were discharged from hospital on average four and six hours respectively after the procedure. Complications during or immediately after the procedure occurred in 5.8% of cases. In the subgroup with clinical follow-up, there was minor bleeding at the access site in 16.4% and hematoma in 14.4%; in the latter group, only one patient had major hematoma requiring therapeutic intervention. No other major complications were recorded and the patients resumed their daily activities on average 7 days after discharge. Image analysis revealed that most of the films were of good quality. CONCLUSION: The use of 4F catheters for diagnostic cardiac catheterization via the femoral approach enables rapid hemostasis and early ambulation, with a low incidence of complications at the access site. This type of catheter provides good quality images and there were no problems in their handling. 4F catheters are therefore a good option to consider for cardiac catheterization, especially when no therapeutic procedures are expected. PMID- 20301985 TI - "Toll-free" access. PMID- 20301986 TI - Hemoptysis in a single lung Fontan: percutaneous approach. AB - BACKGROUND: The Fontan procedure is sometimes the last palliative surgery for complex congenital heart disease with single-ventricle physiology. According to some authors, atrial-baffle fenestrations with right-to-left shunts have improved the surgical outcome of the Fontan operation. Percutaneous fenestration closure at a later stage may increase saturations and reduce the risk of embolic complications. A case could be made that the fenestration should be left patent if the patient, having lost the continuity of the pulmonary artery to one lung, only has a single functional lung. CASE REPORT: The case of an 11-year-old boy with a severe form of Ebstein anomaly is reported. He had undergone a fenestrated Fontan procedure and had lost the continuity to the left pulmonary artery. Further intervention was discouraged at other centers but he was eventually referred to our institution due to increasing cyanosis and severe hemoptysis. Several right-sided arteriovenous pulmonary malformations and collateral arteries were embolized percutaneously; a major right-to-left shunt at the fenestration in the atrial baffle was also occluded with an Amplatzer device. His saturation rose from 78 to 94% and his exercise tolerance increased, without further hemoptysis. PMID- 20301987 TI - From the discovery of the circulation of the blood to the first steps in hemorheology: part 2. AB - In the second and last part of this article, the contributions of two more brilliant figures are described in two sections, A and B, respectively Marcello Malpighi and Antonie van Leeuwenhoek. Through the originality of their work, both confirmed the pioneer William Harvey's observations and went on to add important details. Malpighi applied the optical microscope, until then used almost exclusively as a mere curiosity, to the in vitro study of the body tissues of various species. Outstanding among these pioneering observations was the visualization, for the first time, of capillary structures and blood corpuscles, on the basis of which he defined the composition of blood and, also for the first time, the concept of its fluidity. Furthermore, Malpighi confirmed the structural and functional continuity of the systemic circulation, which Harvey had been unable to demonstrate. Although van Leeuwenhoek lacked an academic education, he was able to see, through lenses he built himself, the microscopic details of the organic and inorganic world around him. Among numerous detailed observations of all types of substances, particularly important were the insights that he obtained into the nature of blood and red blood cells, to which he attributed the color of arterial and venous blood. He calculated the size of erythrocytes with striking accuracy. He was able to distinguish arterial from venous blood, confirmed the heart's function as the force behind the propulsion of the blood through the arteries and of the rhythmic nature of the pulse, and elucidated the return of the blood to the heart by different vessels, the veins. He visualized the bifurcation of the arteries into increasingly narrow vessels until they gave way to capillary networks, which in turn became successively wider venous channels. Van Leeuwenhoek demonstrated the existence of arterial-venous anastomoses. He discovered erythrocyte sedimentation and deformability (their shape varying from the original discoid or oval form, observed in larger vascular segments, to flat forms, adapted to the diameter of narrower vessels). In the process he defined the characteristics of red cell circulation and the alterations that follow blood coagulation, and was thus a perceptive pioneer of the concepts of hemorheology applied to medicine. PMID- 20301988 TI - Bilateral papillary muscle infarction in a chagasic patient. AB - We report a case of a 59-year-old patient diagnosed with chagasic cardiomyopathy, who manifested sudden heart failure while hospitalized, evolving to death due to cardiogenic and septic shock. Anatomical-pathological studies revealed infarction of the papillary muscles together with histological changes compatible with 48 to 72 hours of evolution. Pulmonary edema was considered the cause of death, probably related to mitral regurgitation of ischemic nature. The cause of the papillary muscle infarction was not elucidated by study of the coronary tree, which presented no signs of recent thrombosis. Explanation for the papillary muscle infarction in this patient may be related to the presence of alterations in microcirculation represented by vasodilation and the consequent phenomenon of "stealing" of blood flow in this territory to the detriment of other areas, or due to the fact that the papillary muscles may represent convergence zones of two distinct coronary circulations. PMID- 20301989 TI - Cardiomyopathy in Churg-Strauss syndrome. AB - The authors present the case of a 56-year-old man, admitted to the hospital twice in ten days for acute coronary syndrome with normal coronary angiograms. In the second hospitalization, the patient had anginal crises that did not respond to anti-ischemic therapy, associated with cough and wheezing. The echocardiogram revealed worsening left ventricular systolic dysfunction. He had no cardiovascular risk factors but there was a history of bronchial asthma, allergic rhinitis and peripheral neuropathy of the left upper limb with paresthesias. Laboratory studies showed eosinophilia, detected in previous blood tests, although more marked than before. Chest X-rays showed non-fixed pulmonary infiltrates and bronchoalveolar lavage revealed increased lymphocytes and eosinophils, suggesting Churg-Strauss syndrome with the probable cardiac manifestation of coronary vasospasm. A cardiac MRI was also performed but was inconclusive due to the patient's intolerance of the exam. PMID- 20301990 TI - Coronary perforation following stent implantation. PMID- 20301991 TI - Arrhythmogenic biventricular dysplasia? PMID- 20301992 TI - Portuguese Registry of Acute Coronary Syndromes: seven years of activity. AB - BACKGROUND: The Portuguese Registry of Acute Coronary Syndromes was established in 2002, with the goal of gathering data on the clinical characteristics, treatment and prognosis of Portuguese patients with acute coronary syndromes (ACS). OBJECTIVE: To report the information collected during the seven years of activity of the Portuguese Registry of ACS (from January 1, 2002 to December 31, 2008). METHODS: The Portuguese Registry of ACS is an observational, prospective and continuous registry, which started on January 1, 2002 and involved 45 Portuguese hospitals. Patients with ST-segment elevation myocardial infarction (STEMI), non-ST segment elevation myocardial infarction (NSTEMI) and unstable angina (UA) were included. Information was collected on 188 variables, including data on clinical presentation, treatment and prognosis of patients with ACS. RESULTS: The registry included 22,482 patients (mean age 66 +/- 13 years, 70% male), distributed as follows: 45.4% STEMI, 41.4% NSTEMI and 13.1% UA. Reperfusion therapy was used in 63% of STEMI patients, ris- ing from 60% in 2002 to 75% in 2008, with an increasing proportion of primary angioplasty relative to fibrinolysis. Aspirin, low molecular weight heparin and glycoprotein IIb/IIIa inhibitors were used in respectively 97%, 88% and 26% of the patient population. A combination of dual antiplatelets, beta-blockers, angiotensin-converting enzyme inhibitors and statins was used in 32% of patients during hospitalization, in 26% on discharge and in 16% six months after the acute event. Coronary angiography was performed in the majority of patients (62%), followed by a coronary revascularization procedure in about a third (38%). Coronary angiography was increasingly used during the period under analysis, with a concomitant increase in revascularization procedures. In-hospital mortality was 5.2% in the overall population (7.7% in STEMI, 3.9% in NSTE-MI and 0.7% in UA), declining significantly over time. Cumulative mortality six months after the acute event was 7.5% (10.2% in STEMI, 6.6% in NSTEMI and 1.5% in UA). CONCLUSION: The Portuguese Registry of ACS has collected crucial information on the clinical characteristics, treatment and prognosis of ACS in Portugal. The reported results reveal discrepancies between the guidelines for ACS treatment and their application in clinical practice. Analysis of the results has identified several issues that require particular attention and future intervention in order to improve ACS treatment and prognosis. PMID- 20301993 TI - Intrapartum ultrasonogram for the determination of fetal occiput position and risk of cesarean section. AB - OBJECTIVE: To evaluate the value of intrapartum ultrasonographically determined occiput position and risk of cesarean section. MATERIAL AND METHOD: Between August 1, 2008 and May 31, 2009, 330 singleton pregnant women, GA 37-42 weeks with cephalic presentation who were in early active phase of labor at Thammasat University hospital were recruited. The fetal occiput position was determined by transabdominal ultrasonography. The occiput posterior defined as cases and non occiput posterior defined as controls. Perinatal outcomes and delivery methods were recorded. Independent sample t-test, Chi-square and multivariable regression were applied for analysis. RESULTS: The incidence of occiput posterior was 29.7%. The abnormal cervical dilatation, cesarean delivery, and newborn weight were statistically significantly higher in cases. 44.9% of cases underwent cesarean section compared to 14.7% of controls. CONCLUSION: Fetal occiput posterior presentation determined in early stage of active labor by ultrasonography was a significant independent risk of cesarean section. PMID- 20301994 TI - Reference centile chart for fetal nuchal translucency, maternal serum PAPP-A and free beta hCG. AB - OBJECTIVE: To create reference centile chart of fetal nuchal translucency maternal serum pregnancy associated plasma protein-A (PAPP-A) and maternal serum free beta human chorionic gonadotropin (beta-hCG) in order to predict preliminarily Down syndrome in Thai fetuses during 10-14 weeks of gestation. MATERIAL AND METHOD: This was a prospective, descriptive cohort study. From 1 January 2004 to 31 December 2006, a total of 1,000 pregnant women during 10-14 weeks of gestation were participated in the present study. Pregnancy outcomes were reviewed from the records. The excluded cases were chromosomal and major structural abnormalities, twin pregnancy and cases resulting in miscarriage or intrauterine death. All women had a scan for nuchal translucency (NT) and had blood taken for measurement of maternal serum PAPP-A and free beta-hCG level. RESULTS: The mean NT was 1.6 +/- 0.8 mm (range 0.3-14 mm). The 5th, 50th and 95th centile of PAPP-A and free beta-hCG during 11-14 weeks of gestation were 1.54-69, 14-28, 51-57 and 24.8-17, 78-47, 181.6-126.5 mIU/mL, respectively. The distribution and the 5% and 95%, lower and upper limits of NT, PAPP-A and free beta-hCG was presented. CONCLUSION: The present study shows that NT measurements increase with increasing gestational age. The mean serum PAPP-A rises and the mean serum-free beta hCG decreases from 10 to 14 weeks of gestation in normal Thai fetuses. These results can be used for reference value to predict fetal Down Syndrome. PMID- 20301995 TI - Antibacterial activity of carbapenem-based combinations againts multidrug resistant Acinetobacter baumannii. AB - BACKGROUND: Multidrug-resistant (MDR) Acinetobacter baumannii are increasingly encountered and frequently susceptible only to colistin with their MIC values close to resistance breakpoint. Antibacterial activity of two carbapenem-based combinations were explored in order to overcome the bacterial resistance. MATERIAL AND METHOD: Thirty clinical isolates of MDRA. baumannii were employed to assess in vitro antibacterial activity of two carbapenem-based regimens. Imipenem combined with colistin and meropenem combined with colistin and sulbactam were the first and second regimens, respectively. All isolates were resistant to imipenem (MIC range: 8-128 microg/ml) and meropenem (MIC range: 64-256 microg/ml) but still susceptible to colistin (MIC range: 0.5-2 microg/ml). The MIC range of sulbactam was 4-64 microg/ml. None of the isolates produced metallo-beta lactamase. RESULTS: Synergistic antibacterial effect of imipenem combined with colistin was observed against 100 percent of A. baumannii isolates by the checkerboard microdilution panel method. In a subsequent time kill study, the most active concentration of this regimen was the combination of imipenem at the fixed concentration of 32 microg/ml and colistin at the 1/4 of the MIC values of each isolate that exerted significantly higher bactericidal activity than imipenem at 32 microg/ml alone and colistin alone at the 1/4 of the MIC values. The scanning electron micrographs demonstrated major cell morphological change and cell wall destruction after 2-hour exposure to this combination. The triple combinations of meropenem, sulbactam and colistin showed synergy against 96.7 percent of MDR A. baumannii while double combinations of either meropenem and sulbactam, meropenem and colistin, and sulbactam and colistin showed synergy effects of 70%, 73.3% and 53.3%, respectively The time kill study using ten isolates also showed better killing effect by the triple combination than any of the double combinations. CONCLUSION: Antibacterial activity against MDR A. baumannii of imipenem plus colistin was superior over any single of the two agents. The addition of sulbactam to meropenem and colistin may further improve their antibacterial activity. The double or triple carbapenem-based combinations offer promising alternatives in the treatment of infections due to MDR A. baumannii. PMID- 20301996 TI - Comparison of continuous infusion versus intermittent infusion of vancomycin in patients with methicillin-resistant Staphylococcus aureus. AB - OBJECTIVE: To compare the pharmacokinetics of vancomycin administration by continuous infusion and intermittent infusion. MATERIAL AND METHOD: A prospective, randomized, two-way crossover study of 12 patients with methicillin resistant Staphylococcus aureus infections was conducted. All patients were randomized to receive vancomycin in both regimens consecutively: (i) infusion of 15 mg/kg of vancomycin as a loading dose for 1 h followed by 30 mg/kg of vancomycin as a continuous infusion over 24 h for 48 h; and (ii) intermittent infusion of 15 mg/kg of vancomycin for 1 h every 12 h for 48 h. Vancomycin pharmacokinetic studies were carried out during hours 24-48 after the start of both regimens. RESULTS: For the continuous infusion regimen, the mean highest steady-state concentration was 24.88 +/- 12.75 microg/ml and the mean lowest steady-state concentration was 19.89 +/- 10.15 microg/ml. For the intermittent infusion regimen, the mean peak and trough serum concentrations were 55.02 +/- 17.36 and 12.43 +/- 12.86 microg/ml, respectively. After 10 days of vancomycin treatment, the MRSA infections were eradicated in all patients. Moreover, during both methods of infusion, no adverse events related to the use of vancomycin were observed. CONCLUSION: Either continuous infusion or intermittent infusion can be used as an effective mode of vancomycin administration to achieve bactericidal activity. PMID- 20301997 TI - Metabolic syndrome and atherosclerotic risk factors as determinants of blood sugar control in diabetic patients: a retrospective cohort study. AB - OBJECTIVE: To examine the effects of metabolic syndrome and atherosclerotic risk factors on blood sugar control in diabetic patients. MATERIAL AND METHOD: This present retrospective cohort study of two hundreds of medical records of diabetes patients treated at the outpatient internal medicine department during the year 2006-2007. Data were collected using a case record form containing biochemical profile characteristics of patients and metabolic components by the World Health Organization (WHO) criteria. The affecting factors to optimal treatment were analyzed to give descriptive (percent = %, mean, SD, median, range) and inferential statistics (odds ratio = OR). RESULTS: There were 200 diabetic patients included in the present study with males of 30.5% and females of 69.5%. Patients who have a higher number of components of criteria of metabolic syndrome tend to have difficulties in controlling their blood sugar (OR for 4 vs. < 3 components: 4.78 95% CI = 1.14-19.97). Patients with younger age groups are more likely to fail to control their blood sugar with OR of 3.87 (95% CI = 1.53-9.76). CONCLUSION: Diabetic patients who have higher components of metabolic syndrome and younger age tend to have difficulties in controlling their blood sugar. However, the association between having atherosclerotic risk factors and outcome of blood sugar control is inconclusive and needs further studies with a larger sample size. PMID- 20301998 TI - Accuracy of the distance between suprasternal notch and superior iliac spine to determine umbilical arterial catheter length. AB - OBJECTIVE: The present study aimed to validate the SSSL in pre-determinating the insertional length between the sixth and tenth thoracic vertebrae (T6-T10) and examine repeatability property. MATERIAL AND METHOD: A prospective recruitment of 52 babies who were placed the umbilical arterial catheter in the NICU, Thammasat University Hospital was performed. Insertional length of the distance between suprasternal notch and superior iliac spine (SSSL) were performed. The catheter tips were verified against anatomical points on chest and abdominal radiograph. The SSSL was measured twice on each patient to indicate repeatability property. RESULTS: All babies (100 percent accuracy) were correctly placed the catheter tips at high placement (T6 to T10) at the first attempt. Repeatability coefficient for repeating measure of the SSSL was 0.7 centimeters. CONCLUSION: The SSSL is repeatable, simple, and perfectly accurate for pre-determination of the umbilical arterial catheter length to position the catheter tip at T6-T10. PMID- 20301999 TI - Boosted p24 antigen assay for early diagnosis of perinatal HIV infection. AB - OBJECTIVE: The authors evaluated the accuracy of in-house boosted-p24 antigen assay for diagnosis of perinatal HIV infection. MATERIAL AND METHOD: The author has retrospectively reviewed the medical records of infants born to HIV-positive mothers. The infants were tested for boosted-p24 antigen assay at the age of 1-2 months and 4-6 months. HIV infection was defined as positive anti-HIV at the age 18 months or older, or had positive HIV-PCR with clinical signs and symptoms compatible with HIV/AIDS. RESULTS: There were 168 infants included in this review and six were HIV-infected. The boosted-p24 antigen assay had the sensitivity, specificity, positive predictive value, and negative predictive value of 33.33%, 98.27%, 50%, and 95.8%, respectively at 1-2 month-old, and 100%, 98.27%, 71.43%, and 100%, respectively at 4-6 month-old. CONCLUSION: Boosted-p24 antigen assay could be a cheaper alternative test to help diagnosis of perinatal HIV infection in infants. The test was very accurate when performed at 4-6 months. PMID- 20302000 TI - Outcomes of very low birth weight infants in Songklanagarind Hospital. AB - OBJECTIVE: To determine the mortality and morbidity rates of very low birth weight (VLBW) infants in Songklanagarind Hospital. MATERIAL AND METHOD: A retrospective study of all infants with birth weight < 1,500 g admitted to the neonatal intensive care unit between January 2003 and December 2006. RESULTS: A total of 178 VLBW infants, met the enrollment criteria, with mean (+/- standard deviation-SD) birth weight and gestational age of 1,123 +/- 273 g and 29 +/- 3 weeks, respectively. Forty-two (23.6%) were referred from other hospitals. The overall mortality rate was 27.0%. Perinatal risk factors of mortality were birth weight < 1,000 g (p < 0.01), congenital anomalies (p < 0.01), and Apgar score at 1 minute < or = 5 (p < 0.01). Among the 130 (73.0%) survivors to discharge, 92 (70.8%) survived without major morbidity. The major morbidities were moderate/severe bronchopulmonary dysplasia, retinopathy of prematurity stage 3, necrotizing enterocolitis stage > or = 2 and intraventricular hemorrhage grade > or = III in 31 (23.8%), 12 (9.2%), 4 (3.1%) and 2 (1.5%) infants, respectively. CONCLUSION: The mortality rate of VLBW infants in Songklanagarind Hospital was similar to other developing countries, although greater than in developed countries. Among survivors, the major morbidity rates were acceptable. PMID- 20302001 TI - A comparison of open and percutaneous pulley release in trigger digits. AB - OBJECTIVE: To compare the results of open surgery with those of percutaneous surgery in patients with trigger digits. MATERIAL AND METHOD: One hundred forty two patients with 160 trigger fingers and thumbs were prospectively randomized to either open (70 patients, 80 digits) or percutaneous (72 patients, 80 digits) surgeries at Ratchaburi Hospital. The operations were performed by one surgeon between May 1, 2007 and Dec 31, 2008. Operative time, postoperative range of motion of the finger proximal interphalangeal joint (PIP) or thumb interphalangeal joint (IP), patient satisfaction score, patient pain score, and surgical complications were assessed at weeks 1, 2, 3, 4, 6, and 8. RESULTS: Trigger digits were successfully treated in eighty digits (100%) of the patients who underwent open surgery and in seventy-nine digits (98.75%) of the patients who underwent percutaneous surgery. Mean operative time, mean postoperative range of motion of the finger PIP or thumb IP, mean postoperative satisfaction score, and mean postoperative patient pain score were not significantly different between the groups. No serious complications were observed in either group. One patient in the percutaneous surgery group underwent open surgery two months later due to pain and locking. CONCLUSION: Percutaneous trigger digit surgery using the full handle knife 45 degrees is effective and safe, and results functional outcomes equal to those with open trigger digit surgery. PMID- 20302002 TI - Comparative mechanical axis deviation after TKA between conventional and CAS procedure. AB - OBJECTIVE: The purpose of the present study was to report the results of radiographic comparisons made between CAS-TKA and conventional TKA. MATERIAL AND METHOD: The authors retrospectively compared 102 knee radiographs from conventional TKA to 84 knees from CAS-TKA. RESULTS: The mean mechanical axis deviation was 2.77 degrees for conventional TKA and 1.80 degrees for CAS-TKA (p = 0.0002). For conventional TKA 42.2% of the results were considered to be outliers versus only 14.3% outlier frequency among the CAS-TKA procedures (p < 0.0001). Only 54.4% of scanograms were proper for the presented analysis due to improper anterior-posterior positioning. Implementation of a corrective standing block eliminated this issue. CONCLUSION: CAS-TKA significantly reduces both margins of error in knee alignment and frequency of outlier compared with conventional TKA. Further investigation to compare long-term results of CAS-TKA with conventional TKA is recommended. PMID- 20302003 TI - One year results of selective laser trabeculoplasty in the treatment of primary open angle glaucoma. AB - OBJECTIVE: To evaluate the efficacy and safety of selective laser trabeculoplasty (SLT) as a treatment of primary open angle glaucoma (POAG). MATERIAL AND METHOD: In a prospective clinical study, 21 eyes suffering from POAG were treated with SLT over inferior 180 degrees of trabecular meshwork. The intraocular pressure (IOP) was measured before and 1 hour, 1 week, and 1, 3, 6, and 12 months after the treatment. The glaucoma medications were continued on the same regimen during the study period. RESULTS: The mean preoperative IOP was 18.6 mmHg (SD 2.2). The mean IOP reduction were 4.9 mmHg (26.3%) 1 hour after SLT, 2.6 mmHg (14.0%) 1 week after SLT, 4.0 mmHg (21.5%) 1 month after SLT, 3.5 mmHg (18.8%) 3 months after SLT, 3.7 mmHg (19.9%) 6 months after SLT, and 3.3 mmHg (17.7%) 12 months after SLT. There were minimal adverse reactions including conjunctival injection and mild anterior chamber reaction. CONCLUSION: SLT is a safe and effective procedure to reduce IOP in POAG patients. PMID- 20302004 TI - Clinical assessment of levocetirizine and budesonide in treatment of persistent allergic rhinitis regarding to symptom severity. AB - OBJECTIVE: To compare effectiveness of levocetirizine and budesonide in treatment of persistent allergic rhinitis (PER) in patients with high and low total symptom scores (TSS). MATERIAL AND METHOD: Randomized, parallel-group study. Patients with PER were randomized to receive levocetirizine 5 mg (n = 50) or budesonide 256 microg (n = 50) daily for 4 week and were followed-up for another 4 weeks post-treatment. TSS combining itching, sneezing, rhinorrhea, daytime and nighttime nasal congestion was recorded daily during and after treatment for an entire period of 8 weeks. Efficacy variables included area under curves depicting reduction and increase in TSSs over time relative to baselines and time to response and symptom relapses. RESULTS: Symptoms were categorized as high and low using a median TSS of 8 as cutoff. Levocetirizine was as effective in control of high and low symptoms except for time to achieve maximum effect (2 days versus 1 week, respectively, p = 0.002) but was more effective in preventing relapses of high symptoms (p = 0.001). Budesonide was more effective against high than low symptoms (p < 0.001) but showed no difference in preventing relapses. Typical response rate of levocetirizine and budesonide were demonstrated in treatment of high symptoms. Levocetirizine achieved its full effectiveness in 2 days while budesonide required 2 weeks. Budesonide at full effect (after 2 weeks) was superior to levocetirizine (p = 0.004) but comparable for the entire treatment of 4 weeks (p =.059) and was inferior to in preventing relapses (p = 0.001). No such difference could be observed between these drugs in control of low symptoms. CONCLUSION: The effectiveness of the drug treatment in the present study is dependent of symptom severity. Levocetirizine bases on its rate of response and relapse was superior to budesonide in treatment of the high symptom group and is comparable in the low symptom group. PMID- 20302005 TI - Digit span and verbal fluency tests in patients with mild cognitive impairment and normal subjects in Thai-community. AB - BACKGROUND: Far too little attention has been paid to the difference of Digit Span test and category verbal fluency test (CVFT) between normal and mild cognitive impairment (MCI) subjects. OBJECTIVE: To investigate the difference of Digit Span test and CVFT between normal subjects and patients with MCI and study the influence of age, gender, and education on the task performance. MATERIAL AND METHOD: The authors collected data of 77 participants diagnosed with amnestic MCI (from 517 participants screened) and 30 normal subjects aged 50 or over enrolled from communities in Bangkok. The Digit Span test and CVFT (semantic fluency and Controlled word association test for letter fluency) were used to evaluate the subjects. RESULTS: MCI patients had significantly lower digit span score, in both Digits Forward and Digits Backward, poorer performance on semantic fluency for animals and fruits and letter fluency test. The logistic regression model of MCI diagnosis showed that only Digits Backward score was a predictor of MCI diagnosis (OR 0.643 for each increment of 1 digit, p = 0.009, 95% confidence interval 0.462 0.896). The cut-off point of Digit Backward score was 4 and yielded sensitivity of 77% and specificity of 57%. Females had lower scores than males in every test except semantic fluency for fruits. The digit span and semantic fluency scores decreased as age increased but letter fluency increased correspondently with age. The digit span and CVFT scores increased in parallel with the increase of education. CONCLUSION: MCI patients had poorer performance on the Digit Span and CVFT tests than normal age and education matched subjects. Digits Backward test can predict the MCI diagnosis. Age, gender and education have an impact on the performance of the tests. PMID- 20302006 TI - Cadmium-exposed population in Mae Sot district, Tak province: 3. Associations between urinary cadmium and renal dysfunction, hypertension, diabetes, and urinary stones. AB - OBJECTIVE: To study the associations between urinary cadmium and renal dysfunction, hypertension, diabetes, and urinary stones in an adult population living in cadmium-contaminated areas in Mae Sot District, Tak Province, Thailand. MATERIAL AND METHOD: Seven hundred ninety five cadmium-exposed adults were screened for urinary cadmium, renal dysfunction, hypertension, diabetes, and urinary stones in 2005. Six selected markers of renal function in the present study were urinary excretion of beta2-microglobulin (beta2-MG), N-acetyl-beta-D glucosaminidase (NAG), total protein and calcium, serum creatinine, and glomerular filtration rate (GFR). RESULTS: The mean age of the study persons was 50-years-old. The overall prevalence rates of hypertension, diabetes, and urinary stones were 33.3%, 6.2%, and 8.9% respectively. The prevalence of increased proteinuria was greatest in those with urinary cadmium levels > or = 15 microg/g creatinine. Urinary excretion of beta2-MG, NAG, and total protein significantly increased with increasing urinary cadmium levels, after adjusting for other co variables by multiple linear regression analysis. However, urinary cadmium was not significantly associated with urinary calcium, serum creatinine, and GFR. The prevalence rates of hypertension, diabetes, and urinary stones did not significantly increase with increasing urinary cadmium levels. Hypertension, diabetes, and urinary stones were also significant predictors of impaired renal function. CONCLUSION: In this population, increasing levels of urinary cadmium are associated with increasing urinary excretion of beta2-MG, NAG, and total protein. Risk for hypertension, diabetes, and urinary stones remains uncertain in relation to cadmium exposure. PMID- 20302007 TI - The evaluation of primary care unit of Mahasarakham Hospital. AB - OBJECTIVE: To evaluate the one-year performance outcome of Community Medical Care Unit (CMU) in Mahasarakham Hospital. MATERIAL AND METHOD: This cross-sectional descriptive study used the CIPP model. The target population was divided into two groups. The first group consisted of the executive committee of Mahasarakham Hospital including one director, five Vice-directors, and 16 CMU paramedical personnel and public health administrators. The second group consisted of 281 randomized people in the service area of CMU, Mahasarakham Hospital. RESULTS: The overall outcome evaluation of both groups was high with mean of 3.53 and 3.86, respectively. The evaluation of context, input, and output was ranked high in both groups while the process ranking was moderate in the first group and high in the other group. The present study proposed that project guidelines be explicit policies, improvement in behavioral service, appropriate workload, adequate parking lot, and network sharing of hospital data bank. CONCLUSION: The quality and efficiency of CMU project are dependent upon explicit policy, well-planned structure of organization, efficient-informative systems, good development plan, and adequate manpower. The personnel should plan the project process and continuously improve the system. CMU project would be neither successful nor beneficial for the development ofpublic health care system if it lacked the participation of the people in the community and associated networks. The results of the present study might be the useful data for improving and developing the pattern of community healthcare service in urban area. PMID- 20302008 TI - Vaginal vault rupture with evisceration of small intestine during coitus. AB - In 2009, a 41-year-old Thai woman who had undergone abdominal hysterectomy 4 months earlier was admitted because of bleeding per vagina without pain during coitus for 1 day. She had undergone pelvic examination that disclosed small intestine in vagina and scanty bleeding of vaginal vault. Closure of the rupture of the vaginal vault during laparotomy was completed, resulting in satisfactory condition. Vaginal vault rupture is a rare condition. Prompt surgical and medical intervention are required to prevent complications. Incidence, risk factors, and management for rupture of the vaginal vault that occurs after total abdominal hysterectomy are discussed. PMID- 20302009 TI - Subungual squamous cell carcinoma masquerading as chronic common infection. AB - Subungual squamous cell carcinoma is a rare disease that has been frequently misdiagnosed as benignity due to lack of awareness among doctors. The author reports a typical case of subungual squamous cell carcinoma in a 49-year-old Thai farmer who presented with a 4-year history of chronic persistent discharging ulcer at the nail bed of the left middle finger after experiencing a minor trauma to the hyponychium. Initially, he was treated as benign infection but the condition did not improve. The nail bed was biopsied and subungual squamous cell carcinoma was finally diagnosed. One small left epitrochlear lymph node and one large left axillary lymph node were palpable. He underwent amputation of the neck of the middle phalanx of the left middle finger and biopsy of ipsilateral epitrochlear lymph node and dissection of the affected axillary tissue. The histological examination confirmed the diagnosis of subungual squamous cell carcinoma with left epitrochlear and axillary lymph node metastasis. Radiotherapy was planned. PMID- 20302010 TI - Presacral fibrosarcoma in childhood: a case report. AB - Presacral fibrosarcoma is a rare malignant tumor in childhood. Because of its rarity in the presacral region, it is often missed from the differential diagnosis of presacral mass in childhood. The authors present a case of large presacral fibrosarcoma involving spinal canal, with an initial presentation of back pain and abnormal gaiting. PMID- 20302011 TI - Immune reconstitution inflammatory syndrome in HIV-infected patients with tuberculosis. AB - Tuberculosis (TB) remains an important problem in patients with human immunodeficiency virus (HIV) infection and acquired immune deficiency syndrome (AIDS). Concomitant administration therapy of both TB and HIV is fraught with difficulties. Despite the fact that the use of highly active antiretroviral therapy (HAART) led to significant improve quality of life and decrease morbidity including mortality-associated to HIV/AIDS, adverse drug effects lead to interruptions in both HIV and TB therapy. In addition, an important problem when HAART is initiated in patients with TB is the possibility of developing immune reconstitution inflammatory syndrome (IRIS). A six-month regimen consisting of isoniazid, rifampicin, pyrazinamide, and ethambutal for two months followed by isoniazid and rifampicin for four months is a standard regimen for the treatment of known or presumed drug-susceptible TB disease. The following strategy may minimize the risk of IRIS. Patients with CD4 cell counts < 100 cells/mm3, efavirenz-based HAART regimen is recommended and should be initiated as soon as the patients can tolerate TB treatment. Patients with CD4 cell counts 100-350 cells/mm3, HAART should be started at two months after TB treatment initiation. HAART should be deferred with closed follow-up of CD4 cell counts if patients have CD4 cell counts > 350 cells/mm3. PMID- 20302012 TI - [Analysis of expression of vesicular transport genes in avesicular cells of the microsporidium Paranosema (Antonospora) locustae]. AB - Long adaptation of microsporidia, a large group fungi-related protozoa, to intracellular lifestyle has resulted in a drastic minimization of parasite cell. Ultrastructural analysis has shown that the Golgi complex of the microsporidia Paranosema (Antonospora) grylli and P. locustae appears as branching or varicose networks of thin tubules. These tubular networks are connected to endoplasmic reticulum, plasma membrane and forming polar tube but have no vesicles. Vesicles were not found even if ultra-fast cryofixation and membrane fusion/uncoating inhibition were used. However, a limited number of genes involved in vesicular transport were found in microsporidia genomes. In this study we used RT-PCR to analyze the content of mRNA transcripts encoding beta and beta' subunits COPI coatomer complex, Sec13 and Sec31 subunits COPII, SNARE-proteins synaptobrevin and syntaxin-like member of SFT family in P. locustae intracellular stages. The level of expression of studied genes was comparable with that of gene encoding alternative oxidase, enzyme envolved in microsporidia core metabolism. Moreover, polyclonal antibodies raised against recombinant Sec13 subunit COPII, expressed in B Escherichia coli, has shown accumulation of the protein is spores and stages of intracellular development as well as its association with membranes. The presence of components of vesicular transport machinery in avesicular microsporidia cells requires their functional analysis. PMID- 20302013 TI - [Cultivation of cells on a surface covered by microspheres with coupled histones]. AB - The use of histones for modification of the surface intended for cultivation of cells was studied. The work was carried out on the cell line 293 of human embryonic kidney transformed by adenovirus (Ad5) and on the cell line BALB/3T3 clone A31 of mouse spontaneous transformed embryonic fibroblasts. We analyzed interaction of cells with histones of different types put on a hydrophobic surface or on dextran microspheres with diameters of 1.0 microm. It was shown, that all histones studied possessed adhesive ability, but their complexes consisting of total and core histones rendered the best influence on adhesion, morphology and growth of the cells in culture. Thus, cross-linked conjugates of histones immobilized on microspheres promoted in a greater degree formation of a network of cellular structures due to formation of intracellular contacts and simultaneous interaction of cells with several microspheres. Comparing with BALB/3T3 clone A31 the cell line 293 showed significant increase in proliferative activity in 11 days of cultivation on microspheres covered with cross-linked conjugates of histones. Our investigations have shown that the microspheres covered with cross-linked conjugates of histones can be used in the further at creation of the three-dimensional porous matrices intended for in vitro formation of tissue-like cellular structures in them. PMID- 20302014 TI - [Nitric oxide in the mechanisms of afferent innervations of arteries of the brain]. AB - Structural elements of afferent innervations of brain arteries in rats such as receptors and nervous fibers, neurons of ganglia jugularis unit and the nucleus of a single way were investigated with the help of histochemical and electron cytochemical methods. The presence of three types of receptors and afferent fibers has been established in vessels. Neurons with positive reaction to NADPH diaphorase have been allocated in the ganglia jugularis unit and the nucleus of a single way (17.4 and 24.5% accordingly). PMID- 20302015 TI - [Interchromatin granule clusters of mouse preovulatory oocytes, organization, molecular composition and possible functions]. AB - At the diplotene stage of meiotic prophase, the nucleus of mouse preovulatory oocytes contains multiple interchromatin granule clusters (IGC). These nuclear compartments are universal and evolutionary conserved and enriched in pre-mRNA splicing factors. Nowadays, IGCs are believed to play an important role in gene expression events and contain different molecular components that allow coupling of many processes from transcription to mRNA export. We obtained the data on the distributions of poly(A)+RNA, hnRNPS A/B, and NXF1/TAP factor of mRNA export. These factors were found to associate with IGCs of mouse preovulatory oocytes. In the present study, we have demonstrated for the first time the dynamics of large IGCs after specific phosphorilation of SR-proteins with okadaic acid, an inhibitor of protein phosphatases. Using electron microscopy, conventional fluorescent and confocal microscopies, as well as microinjections of olygonucleotide probes in mouse oocytes, some features of structural organization and molecular compositions of IGCs in the nuclei of mouse oocyte from antral follicles were established. Possible roles of IGCs in pre-mRNA metabolism and the participation of these structures in mRNA export are discussed. PMID- 20302016 TI - [Comparative research of normal and transformed fibroblast spreading. The role of microfilament polymerization and actin-myosin contractility]. AB - Polymerization of microfilaments and their subsequent rearrangements under control of actin-myosin interactions are two main processes underlined morphogenetic reactions of cells. We studied their role during spreading of normal and transformed REF52tetRas fibroblasts with adjustable ras oncogene expression. Treatment with inhibitors of cell contractility (Y27532 or blebbistatin) led to disappearance of actin bundles and focal adhesions, but both normal and transformed cells preserved high pseudopodial activity. Spreading was considerably accelerated in normal cells and less accelerated in ras-transformed cells under these conditions. When actin polymerization was suppressed with low concentrations of latrunculin A, stress-fibrills and focal contacts were preserved, but lamellipodial activity was lost in normal cells, so spreading was dramatically inhibited. In the case of transformed fibroblasts, actin bundles and focal adhesions virtually disappeared, but pseudopofial activity was not lost and spreading was suppressed to a lesser extent. Therefore, the most essential process in regulation of cell spreading and polarization is microfilament polymerization at the leading edge. Incidentally, ras-transformed cells are less sensitive to inhibitors affecting cytoskeletal structure than non-transformed ones. Possible mechanisms underlying these diversities are discussed. PMID- 20302017 TI - [Somatic polyploidy associated metabolic changes revealed by modular biology]. AB - Excessive somatic polyploidy usually accompanies physiologic and pathologic overload and it is generally accepted as a symptom of pathology. At the same time, polyploidy cells exist in most fungal, plant, mollusk, fish, bird and mammalian tissues confirming their great evolutionary success. The secret of this success remains enigmatic. Since transcriptome rearrangements usually start with metabolic flux redistribution, we decided to investigate firstly the effects of polyploidy on cell metabolism. Using multitest approach of modular biology and databases Entrez Gene, RefSeq, GNF SymAtlas, Gene Ontology, KEGG, BioCarta; MsigDb, Reactome, GenMAPP, and HumanCyc, we performed detailed comparison of metabolic genes expression in human and mouse organs with reciprocal pattern of polyploidy (i. e. in the heart and in the liver). Pairwise criss-cross comparison of diploid vs. polyploid organs allowed removing species- and tissue-specific effects. From our results, polyploidy is associated with rearrangements of main metabolic pathways. We found deep depression of mitochondrial processes, features of autophagia, and increased carbohydrate degradation and lipid biosynthesis. Taken together, these changes pointed to the energy and oxygen deprivation. We also found clear indications of enhanced oxidative stress protection. The major of them are triggering of pentose-phosphate pathway, depression of mitochondria cytoplasm electron shuttles, and impartment of electron flows across 1 (NADH dehydrogenase) and IV (cytochrome c-oxydase) breath complexes. We suggest that all these changes are necessary for the increase in metabolic plasticity and for the protection of replicating DNA from oxidative damage. PMID- 20302018 TI - [Comparison of crude lysate pellets of isogenic strains of yeast with different prion composition: identification of a set of prion-associated proteins]. AB - A new approach: comparative analysis of proteins of the pellets of crude cell lysates of isogenic strains of Saccharomyces cerevisiae differing by their prion composition permitted to identify a large group of prion-associated proteins in yeast cells. 2D-electrophoresis followed by MALDI-analysis of a recipient [psi-] strain and of [PSI+] cytoductant led to identification of 35 proteins whose aggregation state responded to a shift of prion(s) content. Approximately half of these proteins belonged to functional groups of chaperones and enzyme involved in glucose metabolism. Notable were also proteins involved in translation, in oxidative stress response and in protein degradation. The data obtained are compared with the results of other groups who used other approaches to detecting proteins involved in prion aggregates. PMID- 20302020 TI - Considering the revised recommendations for antibiotic prophylaxis in patients with valvular disease. PMID- 20302019 TI - [The effect of red pigment on amyloidization of yeast proteins]. AB - Amyloid bound thioflavine T fluorescence was studied in the lysates of yeast strains carrying mutations in genes ADE1 or ADE2 and accumulating red pigment, a result of polymerization of aminoimidazoleribotide (an intermediate of adenine biosynthesis). The fluorescence is drastically enhanced in the case of cells grown in media containing high concentration of adenine (100 mg/l) that blocks accumulation of red pigment. Blocks at first stages of purine biosynthesis de novo also impede red pigment and lead to the same effect on thioflavine fluorescence. At the same time induction of mutations in genes ADE1 or ADE2 in originally white prototrophic strains leads to considerable drop of fluorescence. A fraction of protein polymers was studied by agarose gel electrophoresis and this permitted to conclude that lowering of fluorescence intensity is indeed connected with the decrease of amyloid amount in cells accumulating red pigment. Model experiments with insulin fibers demonstrate that red pigment binds fibrils and blocks their interaction with Thioflavine T. 2D-electrophoretic comparison of pellet proteins of red and white isogenic strains, followed by MALDI, allowed identification of 23 pigment-dependent proteins. These proteins mostly belong to functional classes of chaperones and proteins, involved in glucose metabolism, closely corresponding to prion-dependent proteins characterized in our previous work. We suppose that, binding amyloid fibrils, red pigment hinders formation of prion aggregates and also, blocking fibril contact with chaperones, impedes prion propagation. PMID- 20302021 TI - What's in your patient's mouth? How lifestyle, disease, and the environment affect the oral cavity. PMID- 20302022 TI - Retroperitoneal fibrosis and obstructive uropathy due to actinomycosis: case report of a treatment approach. AB - An actinomycotic retroperitoneal infection usually occurs in the presence of an intrauterine device (IUD). It can result in pelvic inflammatory disease and diffuse retroperitoneal fibrosis. A 39-year-old patient was admitted to the emergency unit with left flank pain. A computed tomography scan of the abdomen showed bilateral hydroureteronephrosis and a retroperitoneal malignant mass. Other tumors were excluded with a colonoscopy and an upper gastrointestinal endoscopy. Results of a fine needle aspiration biopsy showed fibrosis compatible with retroperitoneal mesenteritis. Double-J stents were placed in both ureters, and immunosuppressive therapy was started. The patient had clinical and radiologic responses to the therapy. A bilateral ureterolysis and sigmoid colon resection were done. The pathology report showed fibrosis and Actinomyces israelii infection. Parenteral and oral penicillins were administered. The probability of an Actinomyces infection in patients with retroperitoneal fibrosis should be kept in mind, especially in cases in which the patient has an intrauterine device. PMID- 20302023 TI - Squamous cell deep carcinoma after abdominal dermolipectomy: a case report. AB - We present a rare case of squamous cell carcinoma that arose deeply in the abdominal wall, 10 years after abdominal dermolipectomy and wall repair by dermal adipose graft was performed. The patient presented a 10-cm-diameter subcutaneous tumor that was ulcerated on its superficial aspect, adherent to deep tissues. After histologic examination, we tried to remove the neoplastic mass in a radical way. The surgical defect was repaired with a bilateral tensor fasciae latae flap. The extension, aggressiveness, and deep localization of the malignancy led to the patient's death. In this article, we also analyze a different hypothesis about the origin of squamous cell deep carcinomas and the related literature. PMID- 20302024 TI - Lethal perianal infection with septic shock: how should we manage this critical condition? AB - Some patients with perianal infection fall into a critical condition with severe sepsis and septic shock (lethal perianal infection). The objective of this study is to clarify the clinicopathological characteristics of, and treatment strategies for, lethal perianal infection. The clinical records of 7 patients with lethal perianal infection were examined. For two rapidly dying cases (within 3 days), we performed resection of the rectum or local anal drainage as a primary management of damage control. These patients were transferred to our center because of septic shock and multiple organ dysfunction syndrome (MODS) and had received insufficient fluid resuscitation in the previous hospital. Another nonsurviving case who died on the 16th day was transferred without MODS and underwent perianal drainage but could not recover from shock, even after repeated surgical procedures were performed. To prevent a perianal infection from becoming lethal, it should be managed as early as possible with sufficient fluid resuscitation with adequate drainage. PMID- 20302025 TI - Retrospectively comparative evaluation of the first- and second-line chemotherapy with campto and oxaliplatin combined with oral tegafur/uracil (UFT)/leucovorin (LV) in patients with metastatic colorectal cancer. AB - Oral tegafur/uracil (UFT), like an intravenous drip with 5-fluorouracil (5 FU)/leucovorin (LV), has been regarded as an active regimen in the treatment of advanced colorectal cancer. In this clinical trial, we evaluate the toxicity and efficacy of regimens containing oral UFT/LV, instead of an intravenous drip with 5-FU/LV, in the treatment of metastatic colorectal cancer. A phase II study involving 39 patients with metastatic colorectal cancer (CRC) who received UFT/LV plus irinotecan (Group A)/oxaliplatin (Group B) alternated with UFT/LV plus oxaliplatin (Group A)/irinotecan (Group B) was evaluated. The overall tumor control rate (CR + PR + SD) was approximately 64%, and median overall survival was approximately 12 months. Of the 547 doses the 39 patients received, 6 events (1.10%) of neutropenia, 5 events (0.91%) of diarrhea, 2 events (0.37%) of stomatitis, and 2 events (0.37%) of anemia were observed. The alternating regimen seems to be effective and well tolerated for patients with metastatic CRC. PMID- 20302026 TI - Clinical importance of vitamin D receptor gene polymorphism in invasive ductal carcinoma. AB - In this study, we aimed to investigate the clinical importance of the vitamin D receptor gene polymorphism in invasive ductal breast cancer. All patients included in the study had clinical T1-2, N0-M0 invasive ductal carcinoma. Patients' demographics, axillary metastasis status, metastatic lymph nodi/total dissected lymph nodes from axilla, histopathologic characteristics of tumors, local recurrences, and survival ratio were assessed. Vitamin D receptor B genotype frequencies in the patient group (P > 0.05) were as follows: B/b, 43 (77%); B/B, 13 (23%). In conclusion, the vitamin D receptor gene B allele does not seem to be related to local recurrence and distant metastasis of invasive ductal cancer of the breast. PMID- 20302027 TI - Intestinal endometriosis: role of laparoscopy in diagnosis and treatment. AB - Endometriosis is a disease in women in which endometrial tissue is found in abnormal sites, frequently in the peritoneum and pelvic viscera. Endometriosis may therefore affect the genital organs, particularly the left ovary, or it may occur elsewhere in the abdomen, principally the digestive tract in the sigmoid rectum. The difficulty of prompt diagnosis of nongenital endometriotic lesions, whose symptoms are usually nonspecific, and the inadequacy of traditional diagnostic approaches mean the disease has time to progress. A case report is used here to show the use of laparoscopy with immediate histologic examination for the prompt diagnosis and intraoperative treatment of intestinal endometriosis. For patients with extragenital endometriosis, laparoscopic resection offers immediate postoperative advantages but also gives gradual relief of symptoms and in some cases improves reproductive capacity; there is also less formation of adhesions in this disease, which by definition tends to cause them, often making a second look indispensable. PMID- 20302028 TI - FDG PET/CT in the detection of recurrent rectal cancer. AB - The purpose of this study was to assess the additional value of combined fluorine 18 (18F)-fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) in the follow-up of rectal cancer after surgery. Forty-eight examinations in 30 patients were evaluated retrospectively. CT and PET components were interpreted separately, and this was followed by a consensus reading. Sites of increased FDG uptake as well as PET/CT findings were categorized as benign (1), equivocal (2), or malignant (3). The standard of reference was histology or clinical and imaging follow-up for at least 6 months. Sensitivity, specificity, positive and negative predictive values, and accuracy for differentiating benign (14/31) from malignant (17/31) uptake sites in the small pelvis were 100%, 64%, 77%, 100%, and 84% for PET/CT, and 100%, 29%, 63%, 100%, and 68% for PET, respectively. Regarding extrapelvic abnormalities, PET/CT was able to distinguish benign (31/88) from malignant (57/88) with a sensitivity, specificity, positive and negative predictive values, and accuracy of 100%, 87%, 93%, 100%, and 95%, compared with 96%, 68%, 85%, 91%, and 86% for PET. The rare case of an FDG uptake of adrenal adenoma is documented. PET/CT is valuable in the staging of rectal cancer, particularly for excluding recurrent disease suspected by PET interpretation alone in a considerable number of patients. PMID- 20302029 TI - Malignancy rates in operated patients with hyperthyroidism in an area of endemic goiter. AB - We aimed to evaluate the incidence of thyroid cancer in Turkish patients with hyperthyroidism who had undergone thyroid surgery. The data of 344 patients who had been operated on for hyperthyroidism between 1998 and 2006 at our center were evaluated retrospectively. Sixty-five of the subjects had single toxic adenomas, 223 had toxic multinodular goiter, and 56 had Graves' disease. In 35 of 344 patients (10.1%), papillary carcinoma was diagnosed. Other forms of thyroid carcinomas were not observed. The rate of carcinoma was found to be 11.6% in patients with toxic multinodular goiter, 7.7% in patients with single toxic adenomas, and 7.1% in patients with Graves' disease. Occult papillary carcinoma was found in 62.9% of all malignancy diagnoses. The primary aim in the surgical treatment of hyperthyroidism should be to abolish the hyperthyroid state. However, the probability of malignancy, especially occult carcinoma, should always be considered. PMID- 20302030 TI - Laparoscopic reoperation with total fundoplication for failed Heller myotomy: is it a possible option? Personal experience and review of literature. AB - Laparoscopic Heller myotomy with antireflux procedure seems the procedure of choice in the treatment of patients with esophageal achalasia. Persistent or recurrent symptoms occur in 10% to 20% of patients. Few reports on reoperation after failed Heller myotomy have been published. No author has reported the realization of a total fundoplication in these patient groups. The aim of this study is to evaluate the efficacy of laparoscopic reoperation with the realization of a total fundoplication after failed Heller myotomy for esophageal achalasia. From 1992 to December 2007, 5 out of a series of 242 patients (2.1%), along with 2 patients operated elsewhere, underwent laparoscopic reintervention for failed Heller myotomy. Symptoms leading to reoperation included persistent dysphagia in 3 patients, recurrent dysphagia in another 3, and heartburn in 1 patient. Mean time from the first to the second operation was 49.7 months (range, 4-180 months). Always, the intervention was completed via a laparoscopic approach and a Nissen-Rossetti fundoplication was realized or left in place after a complete Heller myotomy. Mean operative time was 160 minutes (range, 60-245 minutes). Mean postoperative hospital stay was 3.1 +/- 1.5 days. No major morbidity or mortality occurred. At a mean follow-up of 16.1 months, reoperation must be considered successful in 5 out of 7 patients (71.4%). The dysphagia DeMeester score fell from 2.71 +/- 0.22 to 0.91 +/- 0.38 postoperatively. The regurgitation score changed from 2.45 +/- 0.34 to 0.68 +/- 0.23. Laparoscopic reoperation for failed Heller myotomy with the realization of a total fundoplication is safe and is associated with good long-term results if performed by an experienced surgeon in a center with a long tradition of esophageal surgery. PMID- 20302031 TI - Case of Bochdalek hernia in the elderly: success with laparotomy. AB - Bochdalek hernia is usually diagnosed in pediatric patients and not in the elderly. In adults, there are some cases resulting in misdiagnosis of pneumonia, pleural effusion, congenital bulla, and pneumothorax by chest roentgenogram. We present here a rare case of Bochdalek hernia in an elderly patient who suffered from sudden back pain and had the hernia repaired with laparotomy. PMID- 20302032 TI - Rationale for selective neck dissection in N+ oral cancer. AB - The most significant prognostic factor is the presence of regional metastasis in patients with oral squamous cell carcinoma (SCC). The radical neck dissection has been the preferred therapeutic modality to neck metastasis for one century. The objective of this study was to analyze the feasibility of selective neck dissection for SCC of the lower sites of the mouth. The charts of a series of 460 cases of SCCs of the inferior floor of the mouth treated in Hospital Heliopolis, Brazil, between 1978 and 2002, were retrospectively reviewed. The pattern of metastatic spread was analyzed in the radical neck dissection according to N stage. In the radical neck dissections, the metastatic spread index for levels IV and V were 5.8% and 4.6%, respectively, for cN0 patients and 9.9% and 5.9%, respectively, for cN+ patients. When level I was the only site of metastasis, this index was 11% and 5.5%, respectively. The indication of a selective neck dissection including levels I-IV is oncologically safe for SCCs of the inferior mouth when level I is clinically compromised. PMID- 20302033 TI - Intestinal obstructions: what has changed so far? AB - The aim of this study is to evaluate the changing factors related to surgery in intestinal obstruction. The surgical records of patients who were operated for intestinal obstruction at Hacettepe University Medical School during the years 1980-1985 and 2000-2005 were evaluated retrospectively. There were 92 patients in group I and 185 patients in group II. The cause of intestinal obstruction was adhesions in 41.30% of the patients in group I and tumors in 45.95% of the patients in group II (P = 0.0001). Patients with peritoneal carcinomatosis constituted 3.26% of the patients in group I and 27.03% of the patients in group II (P = 0.0001). Abdominal computed tomography was not used in the first group and was used in 60.54% of those in the second group (P = 0.0001). Complications were seen in 40.54% of patients in the second group and in 26.08% of patients in the first group (P = 0.01). During the past 20 years, changes have occurred that were related to causes, diagnostic tools, and nutritional support for patients undergoing surgery for intestinal obstruction. Despite these changes, no changes in length of hospital stay or mortality have been reported. Intestinal obstruction due to peritoneal carcinomatosis seems to be a growing problem. PMID- 20302034 TI - The genetics of abdominal aortic aneurysms: a comprehensive meta-analysis involving eight candidate genes in over 16,700 patients. AB - Abdominal aortic aneurysms (AAAs) are thought to be multifactorial in etiology. A variety of susceptibility genes have been associated, but definitive conclusions have been difficult to draw and are partly hampered by the small number of patients in each study. We undertook a comprehensive meta-analysis on any gene that was investigated in a case-control model of AAA. A comprehensive, genetic meta-analysis of all genes investigated by using an allelic-association, case control model in AAA was conducted. Electronic databases were searched through July 2009 for any candidate gene in AAA. Odds ratio (OR) and 95% confidence intervals (CIs) were determined for each gene-disease association by using fixed- and random-effect models. Twenty studies in 7 candidate genes were analysed among 16,748 individuals (i.e., 7891 patients and 8857 controls). Of the 8 genes studied, 5 genes were associated with AAA. The angiotensin-1 converting enzyme (ACE) insertion/deletion polymorphism (I/D) showed a significant association in both a dominant model (OR, 1.35; 95% CI, 1.17 to 1.56; P < 0.0001) and a recessive model (OR 1.24; 95% CI, 1.08 to 1.42; P < 0.00001). The pooled ORs for the C677T variant of 5,10-methyltetrahydrofolate reductase (MTHFR) were 1.34 (95% CI, 1.08 to 1.65; P = 0.007) for the dominant model and 1.16 (95% CI, 0.81 to 1.67; P = 0.41) for a recessive model. There was also significance in the dominant model of the angiotensin-1 receptor polymorphism (AT1R) A1166C (OR, 1.94; 95% CI, 1.66 to 2.28; P < 0.00001) and in the dominant (95% CI, 1.18 to 2.11; P = 0.002) and recessive (OR, 1.51; 95% CI, 1.13 to 2.02; P = 0.006) models of the interleukin-10 1082 polymorphism. The MMP-3 nt-1612 polymorphism was also significant in the dominant (OR, 1.4; 95% CI, 1.12 to 1.76; P = 0.003) and recessive (OR 1.3; 95% CI, 1.05 to 1.61; P = 0.02) models. In conclusion, there is a genetic basis to sporadic aortic aneurysms. Patients with the ACE/D and MTHFR/677T, AT1R/C, IL-10/A, and MMP-3 nt-1612 polymorphisms are at an increased risk of developing this condition. PMID- 20302035 TI - Initial ultrasonographic assessment for blunt abdominal trauma: is it a reliable diagnostic modality for emergency laparotomy? AB - Abdominal ultrasound has been proposed as a tool for the evaluation of blunt abdominal trauma. The aim of this study was to evaluate ultrasound's ability to identify intraabdominal injuries that require surgical treatment. Data from 1463 patients were examined retrospectively during a 2-year time period, which were ultrasonographically evaluated for blunt abdominal injury. Hemoperitoneum and abdominal visceral injury were correctly detected by ultrasound with 88% sensitivity and 96.8% specificity. The results are in accordance with the international literature. PMID- 20302036 TI - Open and laparoscopic repair of Spigelian hernia. AB - Spigelian hernia is an uncommon ventral wall hernia. Because of the infrequent occurrence of a Spigelian hernia, the optimal surgical repair technique is not patently established in the surgical literature. A series of 4 consecutive patients who underwent surgical repair of a Spigelian hernia is reported with complete long-term follow-up. Each patient was referred for evaluation of point tenderness of the lower abdominal wall. A hernia bulge was found in the Spigelian hernia belt during physical examination of each patient. Clinical awareness of the Spigelian hernia by physical examination occurred best by palpation of the abdominal wall with the patient coughing or straining while in the standing position. The first Spigelian hernia was surgically repaired by an open procedure with primary fascial closure of the hernia defect reinforced with an onlay mesh. A laparoscopic transabdominal preperitoneal mesh repair was performed in the remaining 3 patients. No recurrence of the Spigelian hernia occurred in any of the patients in this series, who were evaluated yearly by physical examination after the hernia repair. The open Spigelian hernia primary fascial repair with onlay mesh and the laparoscopic transabdominal preperitoneal Spigelian hernia mesh repair were uncomplicated surgical procedures that required customary and normal surgical technical skill. PMID- 20302037 TI - Visceral fat volume and surgical outcomes of colorectal resection. AB - As the impact of visceral fat volume on surgical outcomes in colorectal resection had not previously been assessed, this study was designed to compare the surgical outcomes of colorectal resection in obese and nonobese patients. From 2004 to 2007, 79 operative patients with colorectal cancer were examined. Of these, 25 were obese (i.e., greater than 100 cm2 visceral fat volume), and 54 were nonobese. Mean operating time was significantly longer in obese than in nonobese patients (P < 0.01). Mean blood loss was significantly greater in obese than in nonobese patients (P < 0.01). Mean blood loss/h was significantly greater in obese than nonobese patients (P < 0.01). Surgical site infection was more common in obese than in nonobese patients, but this difference was not statistically significant. In conclusion, this study suggested that a visceral fat volume of greater than 100 cm2 may be one of the risk factors in colorectal resection. PMID- 20302038 TI - Enhancement effect of ethanol on lipopolysaccharide-induced procoagulant status in human umbilical endothelial cells. AB - In spite of the inhibitory effects of ethanol (EtOH) on platelet function, soft blood clots are often observed in cadaveric blood in cases of sudden death after alcohol ingestion. In order to resolve this discrepancy, we have focused on the role of vascular endothelial cells. We tried to investigate the effects of EtOH and LPS on endothelial cells from various perspectives; thrombogenic factor (Von Willebrand factor, VWF), fibrinolytic factor (tissue plasminogen activator, tPA) and inflammatory factor (Interleukin-6, IL-6). Human umbilical vein endothelial cells (HUVECs) were incubated with various concentrations of EtOH (0-160 mM) with or without LPS. Treatment with EtOH and LPS increased VWF release from HUVECs without enhancement mRNA expression. Treatment with 40 mM of EtOH also increased IL-6 release from HUVECs without enhancement mRNA expression. Although EtOH inhibited LPS-induced IL-6 mRNA expression, 20 mM of EtOH still had an increasing effect on the release of IL-6. These doses of EtOH are consistent with a moderate drunkenness level in a normal person. On the other hand, mRNA expression and release reaction of tPA were not affected by EtOH and LPS addition. In conclusion, EtOH enhances procoagulant status via VWF release and IL-6 production cooperation with LPS and may contribute to soft blood clot formation in cadaveric blood. PMID- 20302039 TI - Collaboration between medical examiner and toxicologist-analyst. AB - Negative effects of the increasing number of toxic substances in the external environment affecting the human organism are highly reflected in everyday forensic practice. In parallel with new circumstances also the methods enabling identification of heterogeneous substances have been developing. Demonstrating evidence is more challenging and sophisticated particularly in cases with proving several xenobiotics including metabolites and their possible interaction. Poison intoxications of unknown origin can represent a diagnostic problem. Consequently close collaboration between involved forensic professionals i.e. medical examiner and forensic toxicologist-analyst is inevitable. The data provided by police investigators are significant as well--investigated circumstances, testimonies and in case of hospitalization detailed data from clinicians. In everyday forensic practice the shortage of medical examiners specialised in toxicology and knowledgeable toxicologists-analysts has been increasingly experienced. The urgent requirement for more specialists arises more frequently not only in suspected fatal poisonings but also in assessing of analysis results particularly in cases of persons directly involved in road traffic accidents, work-related injuries, etc. The number of cases requiring detecting psychoactive substances is also increasing. On the other hand recent experience demands expanding the spectrum and increasing the number of indications of toxicological analyses from medical examiners involved in performing autopsies. At present the Slovak forensic workplaces are in the process of being equipped with instrumentation designed for expanding the spectrum of toxicological analyses and improving their quality. There hence emerges a need for developing the contemporary concept of Slovak forensic toxicology with respect to both organizational and methodological aspects focused on better interaction of activities carried out by medical examiners and toxicologist-analysts. The essential part of developing the coordination of both expert groups is also postgraduate education with an emphasis on improving mutual recognition principles of their work. PMID- 20302040 TI - [Impact of acute alcoholism on the women's mortality in the northern region of Slovak Republic]. AB - Problem of women's alcoholism doesn't belong among main topics of Slovak or Czech public discussions. Though everyone meeting the phenomenon of women's alcoholism can feel the fatal consequences of this mistake, our society used to perceive alcoholism as a men's problem. The authors performed the complex analysis of the mortuary files with particular focusing on the cases of women's deaths caused by alcohol intoxication, and the cases of deaths where an alcohol played the dominating role, in the northern regions of Slovak republic. Submitted article is author's next referring to urgent need of public discussion concerning the alcohol consumption in Slovakia, the phenomenon being widely tolerated by the society. PMID- 20302041 TI - [[Determination and evaluation of the influence of addictive drugs on drivers of motor vehicles in Germany]]. PMID- 20302042 TI - Childbirth in the land of Utopia. PMID- 20302043 TI - Stop TV portraying childbirth as dangerous. PMID- 20302044 TI - Humanising birth in Brazil. PMID- 20302045 TI - Time to make midwifery matter in Ireland. PMID- 20302046 TI - Hope for Grace Kodindo. PMID- 20302047 TI - Birthing the creative mother. PMID- 20302048 TI - Phenomenological qualitative interviewing and the novice researcher. PMID- 20302049 TI - Midwives and mental health: the need for postnatal clarity. Part 2: the midwife's role. PMID- 20302050 TI - The importance of interprofessional learning. PMID- 20302051 TI - Reaching out in Milton Keynes. PMID- 20302052 TI - Research unwrapped: Diagnosing active labour. PMID- 20302053 TI - Midwifery basics: understanding research (4). Data collection methods and measurement. PMID- 20302054 TI - A medical mystery. PMID- 20302056 TI - Children's trusts look set to improve with new legislation. PMID- 20302057 TI - Online directory aims to prevent cases slipping through the net. PMID- 20302058 TI - Philosophical shift. PMID- 20302059 TI - Nurse-facilitated discharge for children and their families. AB - This article explores the introduction of nurse-facilitated discharge in one children's day care unit. It highlights how a need for change to the discharge procedure was established and how the practice was developed, successfully introduced and subsequently reviewed. The author concludes that the process has improved patients' experience with families no longer waiting hours for a consultant to discharge them. It has relieved bed pressures and empowered staff to extend the process to inpatient children's wards. PMID- 20302060 TI - Caring for young people with chronic illness: a case study. AB - This article is a case study of a 16-year-old female with congenital muscular dystrophy. It aims to raise awareness of some of the issues associated with complex illness during adolescence, particularly the transition from child to adult services. To improve care it is argued that the needs and values of the young person should be respected and interventions planned locally with the young person and their family where appropriate. PMID- 20302061 TI - Cardiovascular assessment in children: assessing pulse and blood pressure. AB - Cardiovascular assessment is an important nursing skill in the assessment and management of acutely ill children and children with chronic conditions. This article outlines the differences in the cardiovascular systems of infants, children and adults, and explains how to provide circulatory assessment in children, focusing on assessing pulse and blood pressure. PMID- 20302062 TI - Medical school curriculum review. PMID- 20302063 TI - Medication use patterns in elderly South Dakota Medicare patients. AB - Optimizing medication use through the evaluation of Potentially Inappropriate Medications (PIMs) has been the focus of a great deal of research. The Centers for Medicare & Medicaid Services (CMS) has created its own definition of PIMs from a variety of existing criteria and has contracted with each state's Quality Improvement Organization (South Dakota Foundation for Medical Care in South Dakota) to work on reducing PIM rates. In South Dakota, 16.4 percent of Medicare beneficiaries who filled a prescription (April 1, 2008, through September 30, 2008) received a PIM. Of the patients receiving PIMs, 13.6 percent received PIMs from two or more categories, and 88.3 percent filled a prescription for at least one of the five most common PIM categories. These five PIM categories were propoxyphene, skeletal muscle relaxants (select agents), nitrofurantoin, oral estrogens and antihistamines (select agents). While there may be rare occasions when these agents are justified, safer or more effective alternatives exist. PMID- 20302064 TI - Medication reconciliation: need for a team approach. PMID- 20302065 TI - Extenuating circumstances: indoor tanning: the preventable epidemic. PMID- 20302066 TI - Striving to become more heart-healthy. PMID- 20302067 TI - [Experimental investigation of atmosphere and water vapor with laser induced breakdown spectroscopy]. AB - The present article investigated the laser induced breakdown spectra of atmosphere molecules as background spectrum for the measurement of airborne particles. The authors detailedly analyzed the spectral lines of oxygen, nitrogen and hydrogen in the laser induced breakdown spectra of atmosphere molecules corresponding to the National Institute of Standards and Technology atomic spectroscopy database line data. In addition, the authors studied the intensity of emitted spectral lines induced by laser breakdown process at different time delays and signal integration width As a result, the authors obtained the conclusion that the intensity of signal depends on variations of delay time strongly, and with a delay time more than 7 micros the interference resulting from the presence of atmosphere molecule can be reduced effectively in the application of laser induced breakdown spectroscopy. Also, the variations in signal integration width have few effects while it is longer than the instrument minimum of 1.1 ms. Besides, this paper investigated the relative intensities of spectral lines of oxygen, nitrogen and hydrogen in the condition of different contents of water vapor in atmosphere, and the authors observed that the intensities of atomic emission line of hydrogen have a linear trend varying with the moisture in atmosphere. These results can be useful for the further application of laser induced breakdown spectroscopy in detecting and monitoring of airborne particles in the air. PMID- 20302068 TI - [Analysis of spectral intensity of fermi resonance of molecules]. AB - Raman spectra of liquid carbon disulfide (CS) and carbon tetrachloride (CCl4) were measured. And the spectral intensity was analyzed using the J. F. Bertran theory and the group theory. The rule about Fermi resonance was obtained from the Raman spectra of carbon disulfide (CS) and carbon tetrachloride (CCL4): (1) The energy can transfer between a fundamental and an overtone frequency about Fermi resonance; the two spectra have the same intensity. The spectral intensity of the two spectra was equal (R=1) about Fermi resonance, when the difference between fundamental of Fermi resonance and overtone of Fermi resonance was very small. (2) The intensity of overtone is stronger than that of fundamental's. (3) The spectrum of Fermi resonance was observed, but the fundamental frequency was not. This article has very good reference value for the assignments in the molecular structure and the research of contents. PMID- 20302069 TI - [Measurement of the cross section in Li(2P)+H2-->LiH+H reaction]. AB - At a Li density of approximately 10(13) cm(-3), the lithium vapor was irradiated in a five-arm stainless steel heat pipe oven containing Li and H2 with pulses of radiation from a N2-laser-pumped dye laser, populating Li(2P) state by the Li(2S- >2P) resonance transition at 670.8 nm. Typical operating pressure of H2 was 60 300 Pa. The cross section for Li(2P)+H2-->LiH+H reaction was measured using method of atomic fluorescence. The decay signal of the time-resolved fluorescence from the 2P-->2S transition was monitored. The decay curve of the Li(2P) can be treated as a single exponential function. The effective lifetimes of the 2P state was obtained. According to the Stern-Volmer equation, a plot of reciprocal of effective lifetimes of the 2P state quenched by H2 against its densities yielded a slope that indicated the total cross section for deactivation and an intercept (at which the H2 pressure is zero) that provided the information about the radiative lifetime of the state. The total quenching (reactive+nonreactive) cross section for deactivation of the 2P state by means of collisions with H2 is (25.1 +/- 4.0) x 10(-16) cm2. The reactive cross section could be obtained using results of the recording of the fluorescence signals with rapid rise in transient regime (<10 ns) Li(2P-->2S) at the different H2 densities. The authors fitted a two-state rate equation model to obtain the cross section sigma (Li(2P)+H2- >LiH+H) = (0.2 +/- 0.1) x 10(-16) cm2. The authors' results imply that reactive collisions occur on average 1/125 as often as quenching collisions. The cross section for reaction is small but not negligible. PMID- 20302070 TI - [Photo-induced electron transfer effects of poly(2-methoxy-5-octyloxy)-p phenylene vinylene/Y2O3:Eu3+ nano-composites]. AB - The photoelectric nano-composites of poly(2-methoxy-5-octyloxy)-p-phenylene vinylene/Y2O3:Eu3+ (PMOCOPV/Y2O3:Eu3+) were prepared by dehydrochlorination in situ polymerization. The result of Fourier transform infrared spectroscopy indicates that PMOCOPV is coated on the surface of Y2O3:Eu3+. Compared with PMOCOPV, the absorption of PMOCOPV/Y2O3:Eu3+ is strengthened, and a red shift of the absorption peak can be clearly observed in the UV-Vis spectrum. Photoluminescence spectroscopy indicates that the maximum emission wavelength of the PMOCOPV/Y2O3:Eu3+ is red-shifted and the intensity of photoluminescence increases in comparison with PMOCOPV. PMOCOPV/Y2O3:Eu3+ shows fluorescence increasing, which involved the inter-molecular photo-induced charge transfer process. The optical band gap of PMOCOPV/Y2O3:Eu3+ decreases. The third-order optical nonlinear susceptibility of PMOCOPV/Y2O3:Eu3+ nano-composites was measured by degenerate four wave mixing. The results show that the third-order nonlinear optical responses of PMOCOPV/Y2O3:Eu3+ nano-composites are enhanced in comparison with PMOCOPV, which can be attributed to inter-molecular photo-induced electron transfer and delocalized pi electron coupling between PMOCOPV and Y2O3:Eu3+. PMID- 20302071 TI - [Study of spectra characteristics of Dy3+ -activated LiSrBO3 phosphor]. AB - The LiSrBO3:Dy3+ phosphor was synthesized by solid-state method. SrCO2 (99.9%), Li2CO3 (99.9%), H3BO3 (99.9%) and Dy2O3 (99.9%) were used as starting materials. After these individual materials were blended and grounded thoroughly in an agate mortar, the homogeneous mixture was heated at 700 degrees C for 2 h in air, and LiSrBO3:Dy3+ phosphors were obtained. The phase present of the samples was characterized by powder X-ray diffraction (XRD) (D/max-rA, Cu Kalpha, 40 kV, 40 mA, lamda = 0.15406 nm). The excitation and emission spectra of these phosphors were measured by a RF-540 photoluminescence spectrophotometer. The emission spectrum of LiSrBO3:Dy3+ phosphor shows several bands at 486, 578 and 668 nm, respectively. The excitation spectrum for 578 nm emission has several excitation bands at 331, 368, 397, 433, 462 and 478 nm, respectively. The effect of Dy3+ concentration on the emission intensity of LiSrBO3:Dy3+ was investigated, and the result shows that the emission intensity of LiSrBO3:Dy3+ phosphor firstly increases with increasing Dy2+ concentration, then decreases, viz. the concentration quenching exists. And the Dy3+ concentration corresponding to the maximal emission intensity is 3 mol%, and the concentration quenching mechanisms are the d-d interaction by Dexter theory. PMID- 20302072 TI - [Preparation and luminescent properties of CaMoO4:Tb3+]. AB - The precursor of the sample CaMoO4:Tb3+ was prepared by the coprecipitation method. TG-DTA spectra show that there is, at 850 degrees C, an energy absorption peak, suggesting that the sample reaches the activation spot of its response. The XRD pattern of the roasted sample shows that CaMoO4:Tb3+, in the single phase, is a representative scheelite structure of CaMoO4, but the peaks shift toward right, implying that tiny crystal defect in the crystal is produced. The defect is likely to be formed by the formation of the holes as two Tb3+ replace three Ca2+ in a cell. The excitation and emission spectra of the sample were investigated and revealed that the defect structure of the sample is in favor of the energy transfer of the characteristic peak (488 nm) of the MoO4(2-) effectively to Tb3+, and makes the 4f electrons of the Tb3+ transit, especially the (7)F6-->(5)D4 electronic transition (488 nm) of the Tb3+, to be greatly strengthened. As a result, the emission spectra with lamdaex=488 nm show that the emission intensity of the spontaneously activated fluorescence MoO4(2-) is greatly weakened, while the green light luminescence intensity of the (5)D4-->(7)F5 transition (544 nm) of the Tb3+ is greatly enhanced. This suggests that the sample CaMoO4:Tb3+ will become the luminescence material with potentially great application value. PMID- 20302073 TI - [Synthesis and properties of nanorod-long afterglow BaAl2O4:Eu2+, Dy3+ phosphor]. AB - The present paper mainly reports a new method to synthesize long afterglow photoluminescent material BaAl2O4:Eu2+, Dy3+. Al(NO3)3.9H2O, Ba(NO3)2, urea, RE(NO3) 3(RE==Eu, Dy) were employed as raw materials, the admixture of H2O/n butanol and H2O/n-butanol/SBS were used as medium, then BaAl2O4:Eu2+, Dy3+ phosphor was achieved by calcining the precursor, which was synthesized by hydrothermal method, at 130 degrees C under reduction atmosphere. The TEM and SEM were used to analyse the morphology and BaAl2O4:Eu2+, Dy3+ synthesized by annealing at 1300 degrees C are all nanorods. The excitation and emission spectra of the phosphor indicated that all of them are broad band, and the main emission peak is around 498 nm, which is due to 5d-->4f transition of Eu2+. The state solid synthesis of the long afterglow phosphor BaAl2O4:Eu2+, Dy3+ generally requires a high calcination temperature, so the products are easily agglomerated, and in this paper the hydrothermal solvothermal synthesis was used, so the synthesized products calcined at 130 degrees degrees C still present well dispersed rod structure, need not milling, and display well luminescence performance. The authors compared the two different conditions of experiment, and found that under the condition without surfactant the authors can still get well dispersed rod structure of BaAl2O4:Eu2+, Dy3+. The method is hopeful to be used in synthesizing other alkali-earth aluminate and silicate and other luminescent materials. PMID- 20302074 TI - [The application of Fourier transform infrared technology in biomedical sphere]. AB - The authors systemically reviewed the development of FTIR technology and its innovative advances during the past fifty years. FTIR technique was once abandoned after initial exploration in biomedical fields, which could not confirm its reliability and credibility. After technological innovation and refined numerical analysis methods, FTIR technique has been applied to a wide range of fields, from single cellular to the complex biomedical tissue components. Nowadays, mature and advanced FTIR technology, such as FTIR microspectrometer and FTIR imaging system, with the aid of pattern recognition and tissue microarray, greatly facilitated the large parallel scale investigation of molecular structure. The recent development of FTIR spectroscopic imaging has enhanced our capability to examine, on a microscopic scale, the spatial distribution of vibrational spectroscopic signatures of materials spanning the physical and biomedical disciplines. The integration of instrumentation development, theoretical analyses to provide guidelines for imaging practice, novel data processing algorithms, and the introduction of the technique to new fields. FTIR technique has helped analyze the complex components of bile stones, which persisted to be a vexing problem and causing high death rate in China. Besides, FTIR technology could provide reliable information in discriminating benign and malignancy. It has been used in detecting thyroid nodules, mammary gland, gastrointestinal tract, cardiovascular and prostate diseases, and parotid gland tissue in combination with ATR detecting device, and has broad clinical application prospects. Till now, FTIR technology has achieved the fast and accurate diagnosis for freshly dissected tissues such as discriminating thyroid carcinoma from nodular goiter intraoperatively. However, further investigations need to be done in this sphere to achieve greater accomplishments. PMID- 20302075 TI - [FTIR study on the synthesis of poly(propylene fumarate) and its copolymer]. AB - Poly(propylene fumarate) (PPF) is one kind of linear biodegradable polyester and the unsaturated double bonds along its main chain can be crosslinked with other olefinic monomers to form three-dimensional networks, and the networks can support tissues. In the present paper, firstly, the intermediate oligomer-bis (2 hydroxypropyl) fumarate (PFP) was synthesized, and then the unsaturated linear polyester PPF was synthesized with the oligomer PFP through melting condensation process. Additionally, on the base of the process, the oligomer bis(2 hydroxypropyl) sebacate (PSP) was synthesized by similar method and then a kind of new copolymer named poly(propylene fumarate-co-propylene sebacate) [P(PF-co PS)] that comprised bis(2-hydroxypropyl) sebacate segments was synthesized with PFP and PSP by melting condensation. During the synthesis process, the structures of bis(2-hdroxypropyl) fumarate, bis(2-hydroxypropyl) sebacate, PPF and P(PF-co PS) were characterized by FTIR The results shows that with the polymerization going along, oligomer bis (2-hydroxypropyl) fumarate and bis(2-hydroxypropyl) sebacate converted to PPF or P(PF-co-PS) gradually. PMID- 20302076 TI - [Study on esterified modification of anthocyanins by FTIR]. AB - Anthocyanins are relatively abundant in vegetables and fruits, which have potential positive health effects. The role of anthocyanins as food coloring agents becomes very important because they can provide attractive bright color of many food products. Nevertheless, the instability of natural anthocyanins was a big obstacle for its usage in food as colorants. The stability of the red radish anthocyanins is significantly improved by modified esterification of the colorant. Usually, the red radish anthocyanins was composed of several components of similar structures. The major methods for determining the structures of anthocyanin colorants involve chromatographic techniques such as TLC, HPLC and HPLC-MS, which are very useful in separation and identification of the components of anthocyanins However, compared to the spectroscopic method, the chromatographic methods are usually complicated and time-consuming during separation and analysis. In the present paper, the authors seek to establish a new, rapid and economic method for the analysis of structural change before and after esterified modification of anthcyanins in view of unique macro-fingerprint characteristics of infrared spectroscopy, which could reflect the whole change of complicated mixture system. The anthocyanins from red radish was esterification modified by reacting with succinic anhydride, and the natural and modified anthocyanins were detected by FTIR The results showed that carbonyl of succinic anhydride was connected with the hydroxyl in glucosyl rings of anthocyanins to form new esterified anthocyanins, which are more stable than the natural one and present attractive bright color as usual. PMID- 20302077 TI - [Study on rapid identification of Cornu saigae tataricae and Cornu antelopis block by Fourier transform infrared spectroscopy]. AB - In the present paper, Fourier transform infrared (FTIR) spectroscopy was used to study the chemical characterizations of cornu saigae tataricae, cornu antelopis block and the mixed sample of them. The results show that there are significant differences between FTIR characterizations of cornu saigae tataricae and cornu antelopes block. The infrared spectra of cornu saigae tataricae are mainly composed of the absorption bands of protein, but in cornu antelopis block the absorption bands of Ca3 (PO4)2 are observed beside protein. And other obvious differences were detected in the FTIR spectra of the two samples: amide bands, C- O stretching vibration bands, and CH stretching vibration bands. The drug of cornu saigae tataricae, cornu antelopis block, and the mixed sample of them could be identified rapidly according to the differences. This experiment gave the scientific data for the researches on chemical components and quality evaluation system of cornu saigae tataricae, and provides the identification method of cornu saigae tataricae and cornu antelopis block. PMID- 20302078 TI - [Comparative study on the infrared fingerprint of Abrus cantoniensis based on the methods of sequential analysis of dual-indexes and cluster analysis]. AB - The methods of sequential analysis of dual-indexes and cluster analysis were utilized to investigate the infrared fingerprints of A. cantoniensis planted in different years and different places in Guangxi, China. The results showed that 6 samples were able to be completely separated only through 13 point smoothing, when the dual-indexes analysis was applied in the present research, and the accurate relationship between these samples could be inspected and expressed by quantitative relationships under 6-dimensional spaces; however, the effect of cluster was bad only through 13 point smoothing of raw spectra, and it was very difficult to find out the regular sequences while the cluster analysis was applied. Furthermore, the 6 samples were able to be completely separated if raw spectra were dealed with 1st derivative after 13 point smoothing, and the clustering effects were more obvious and 6 samples of A. cantoniensis were completely separated. The above two methods could be used to evaluate the quality of Chinese medicinal materials easily when the sample was not excessive quantitatively, but the method of dual-indexes analysis was more difficult than the clustering analysis if the sample size was too large, since a mass of data such as common peak ratio and variation peak ratio of the IR fingerprint spectra were processed and analyzed statistically, while this method could accurately find out the closest relationship between any samples through comparing the quantitative relationships of common peak ratio and variation peak ratio of each sample under 6-dimensional space; the precision of cluster analysis was less than dual-indexes analysis, but it was more convenient than dual-indexes analysis when large sample data were analysed. Finally the above two methods all showed that the chemical composition of the A. cantoniensis was similar in the same cultivated area, but the difference in chemical composition of A. cantoniensis in different years was distinct even they were in the same place. PMID- 20302079 TI - [Research on the effective signal extraction in the noninvasive blood glucose sensing by near infrared spectroscopy]. AB - Diabetes seriously endanger human health, and noninvasive glucose sensing is the expectation of both doctors and patients. Physiological background is complicated, volatile and mixed with a variety of tissue information, resulting in direct measurement of the body's near infrared spectra difficult to truly reflect the concentration change in glucose. As a matter of fact, blood volume is always changing, but human tissue background and the concentration of blood components are constant in a short period. Taking advantage of this, subtracted blood volume spectrometry is propounded, which could eliminate the interference of human tissue background and obtain effective spectrum information of blood. To verify the effectiveness of the method, a experimental system was developed. The system noise is better than 20 microAU, and the signal to noise ratio of the effective spectrum signal at 1250 nm is 20,000:1. Finally, the feasibility and advantages of subtracted blood volume spectrometry are clarified in clinical application of near infrared non-invasive glucose sensing. PMID- 20302080 TI - [Analysis and comparison of daxueteng and their extracts by FTIR]. AB - The present study is to compare and analyze Sargentodora cuneata (oliv) Rehd. etwils herbs, the aqueous, anthraquinone extracts and residue in Jiang Xi and An Hui quickly and undamagedly by Fourier transform infrared spectroscopy(FTIR) and two-dimensional correlation spectroscopy. In the spectra of DaXueTeng, there are two strong peak areas at about 1400-1620 cm(-1) and 1000-1200 cm(-1), and it was concluded that DaXueTeng contains much glycoside and anthraquinone. Anthraquinone extracts only exhibit strong peaks of 1400-1620 cm(-1) which were stronger than that of 1000-1200 cm(-1), and this illustrated that this method was adapted to extracting anthraquinone; then aqueous only show powerful peaks of 1000-1200 cm( 1), so the authors know that the craftwork was suitable for extracting glycoside; finally, the authors also found that the residue of DaXueTeng contained much calcium oxalate. All of these illustrated that FTIR could not only analyze and identify traditional Chinese medicine (TCM) and extract components, but also discriminate contents of different extracts of TCM. The authors developed the new method to analyze and evaluate the DaXueTeng and their pharmacodynamic extracts successfully. PMID- 20302081 TI - [Assessment of cerebral oxygen saturation using near infrared spectroscopy under driver fatigue state]. AB - The objective of the present study is to assess the cerebral saturation under driver fatigue based on the near infrared spectroscopy (NIRS) signals. Twenty healthy male subjects were randomly divided into two groups: A-group (study group) and B-group (control group). All subjects were required to be well rested before the experiment. In A-group the subjects were required to perform the simulated driving task for 3 hours. Cerebral oxygenation signal was monitored for 20 minutes prior to and after the prescribed task period from the left frontal lobe. The results show that cerebral oxygen saturation was found to be significantly lower following 3-hour driving in the task group compared to that in the control group (F = 15.92, p < 0.001). Also a significant difference in selective reaction time was observed between the task group and control group during the post task period (p = 0.021). These findings showed that the cerebral blood oxygen saturation was closely related to the driver fatigue. The decline of the cerebral oxygen saturation might indicate a reduced cerebral oxygen delivery. This suggests that NIRS could provide a non-invasive method to detect driver fatigue. PMID- 20302082 TI - [Geographical origin discrimination of Auricularia auricula using variable selection method of modeling power]. AB - Near infrared (NIR) spectroscopy combined with variable selection method of modeling power was investigated for the fast and accurate geographical origin discrimination of auricularia auricula. A total of 240 samples of auriculari auricula were collected in the market, and the spectra of all samples were scanned within the spectral region of 1100-2500 nm. The calibration set was composed of 180 (45 samples for each origin) samples, and the remaining 60 samples were employed as the validation set. The optimal partial least squares (PLS) discriminant model was achieved after performance comparison of different preprocessing (Savitzky-Golay smoothing, standard normal variate, 1-derivative, and 2-derivative). The effective wavelengths, which were selected by modeling power (MP) and used as input data matrix of least squares-support vector machine (LS-SVM), were employed for the development of modeling power-least squares support vector machine (MP-LS-SVM) model. Radial basis function (RBF) kernel was applied as kernel function. Three threshold methods for variable selection by modeling power were applied in MP-LSSVM models, and there were the values of modeling power higher than 0.95, higher than 0.90, and higher than 0.90 combined with peak location (0.90+Peak). The correct recognition ratio in the validation set was used as evaluation standards. The absolute error of prediction was set as 0.1, 0.2 and 0.5, which showed the wrong recognition threshold value. The results indicated that the MP-LS-SVM (0.90+Peak) model could achieve the optimal performance in all three absolute error standards (0.1, 0.2 and 0.5), and the correct recognition ratio was 98.3%, 100% and 100%, respectively. The variable selection threshold (0.90+Peak) was the most suitable one in the application of modeling power. It was concluded that modeling power was an effective variable selection method, and near infrared spectroscopy combined with MP-LS-SVM model was successfully applied for the origin discrimination of auricularia auricula, and an excellent prediction precision was also achieved. PMID- 20302083 TI - [Noninvasive detection of the concentrations of pigments in pork tissue using near infrared spectroscopy]. AB - Based on the absorption spectra of hemoglobin and myoglobin in the near infrared band, the concentrations of these pigments in the biological tissues can be obtained using near infrared spectroscopy (NIRS) by detecting the intensity attenuation of the emitted light compared with the incident light. Based on the steady-state spatially resolved NIRS, the prototype for detecting the concentrations of tissue hemoglobin and myoglobin was independently developed by our group. The probe consisted of an LED light source which could emit three different wavelengths in the near infrared band, and two detectors which were placed on the same line with and at the distances of 30/40 mm to the LED. The pigment concentrations of two pieces of pork, one from the erector spinae and the other from the rectus femoris, were detected using this prototype. The total concentrations of hemoglobin and myoglobin (c(total)) were (6.42 + 1.51) micromol x L(-1) in the erector spinae, and (15.48 +/- 4.54) micromol x L(-1) in the rectus femoris, respectively. The myoglobin was dominant in both of the results. These were consistent with the recent empirical reports. In summary, the NIRS method and prototype are authentic in detecting the pigment concentrations of pork tissue non-invasively, real-time, directly and conveniently. PMID- 20302084 TI - [Determination of hard rate of licorice (Glycyrrhiza uralensis F.) seeds using near infrared reflectance spectroscopy]. AB - With 112 licorice seed samples with different hard rates ranging from 0.3% to 99.3%, harvested in different years from 2002 to 2007 and from different locations of China including Xinjiang municipality, Ningxia province, Inner Mongolia municipality, Gansu province, Shanxi province and Heilongjiang province, a model for determining hard rate of licorice seeds was tried to be built by near infrared reflectance spectroscopy with quantitative partial least squares (QPLS). All the seeds samples were divided into two groups: calibration set (including 84 samples) and validation set (including 28 samples). The influences of different spectral regions, different main components and different calibration samples on the prediction results were compared. The result indicated that the spectral regions of 4000-8000, 5000-9000, 5000-8000, 5000-7000 and 5000-6000 cm(-1) all had satisfied and similar prediction results, then 5000-6000 cm(-1) was regarded as the optimum spectral region for building the model because of its faster operation speed. The model with 6 main components had better relative high determination coefficient (R2) and low standard errors and absolute errors. With the spectral range from 5000 to 6000 cm(-1) and 6 main components, there was a better fitting between the predictive value and true value. Determination coefficients (R2) of calibration and validation sets are 90.23% and 91.24%, the coefficients of correlation are 0.9532 and 0.9579, the standard errors are 10.31 and 9.72, and the average absolute errors are 8.01% and 7.45% respectively. Even with different calibration samples, the models have high determination coefficient (R2 over 90%), low standard errors (about 10.00) and low absolute errors (about 7.90%). The building of NIR model for determining hard rate of licorice seeds could promote the application of hard seeds in cultivation. PMID- 20302085 TI - [Quickly determination of titanium dioxide content in juice based on Vis/NIR spectroscopy technique]. AB - In order to quickly and accurately detect the content of titanium dioxide in the juice, a method combining chemometrics and Vis/NIR spectroscopy technique was used in the present study. First, the content of titanium dioxide in the juice sample was determined by using spectrophotometer and standard curve of titanium dioxide. Then, different amount of pure titanium dioxide was adulterated into the juice collected from the market to prepare eight different content samples. A total of 320 juice samples were studied. Two hundred samples (25 samples for each content) were randomly selected from the 320 samples to be the calibration set while the other 120 samples (15 samples for each content) were selected as the validation set. The spectra of juice were within near infrared (NIR) and mid infrared (MIR). First six different preprocessing methods were compared, such as standard normal variate (SNV), moving average, derivative and multivariate scatter correction (MSC). The optimal partial least squares(PLS)was built after the performance comparison of different preprocessing methods. Another algorithm, principal component-artificial neural network (PC-ANN), was also used: first, the original spectral date was processed using principal component analysis, the best number of principal components (PCs) was selected, and the scores of these PCs would be taken as the input of the artificial neural network (ANN). The PC-ANN was trained with samples in the calibration collection and the samples in prediction set were predicted. After comparison, MSC was found to be the most appropriate spectral preprocessing method and the best number of PCs is 7. The correlation coefficients (R2) between the real values and predicted ones by discriminant analysis model were 0.9008 (PLS) and 0.8684 (PC-ANN) respectively. The root mean standard errors of prediction (RMSEP) by PLS and PC-ANN were 0.05 (PLS) and 0.04 (PC-ANN) respectively. The result indicated that the content of titanium dioxide in the juice powder to be quickly detected by nondestructive determination method was very feasible and laid a solid foundation for setting up the titanium dioxide content forecasting model of juice powder. PMID- 20302086 TI - [Study on the identification of ganoderma by multi-steps infrared macro fingerprint method]. AB - Ganoderma lucidum, ganoderma atrum, ganderma tsugae Murr. and ganoderma lipsiense can be discriminated and identified by using multi-steps infrared macro fingerprint method. The 1D-1R spectra, based on the peaks intensity at 1153 and 1078 cm(-1), which are the fingerprint characteristic peaks of glucoside compounds, show that the content of glucoside compounds of them was in the order of: ganoderma lucidum>ganoderma atrum>ganderma tsugae Murr. >ganoderma lipsiense. Generally, the second derivative IR spectra can clearly enhance the spectra resolution. In the range of 1600-1720 cm(-1), the position and sharpness of characteristics peaks were very different, and it's proved that amino acid peptide compounds of them were different. In the 2D-IR spectra, four of them have the same autopeak at 1100 cm(-1), which is the autopeaks of glucoside, but the number of autopeaks of ganoderma lucidum was 4 and its strongest autopeak was 1040 cm(-1), while 5 autopeaks, 4 autopeaks and 5 autopeaks were for ganoderma atrum, ganderma tsugae Murr. and ganoderma lipsiense respectively, and their strongest autopeaks were 1040, 1139, 1140 and 1134 cm(-1) respectively. The multi steps infrared maro-fingerprint identification testified that the contents of glucoside compounds and amino acid peptide compounds in these four kinds of ganoderma are different. It's proved that multi-steps infrared maro-fingerprint method can be used to analyze and distinguish ganoderma lucidum, ganoderma atrum, ganderma tsugae Murr. and ganoderma lipsiense. PMID- 20302087 TI - [Raman spectra of monkey cerebral cortex tissue]. AB - Monkey cerebral cortex, an important part in the brain to control action and thought activities, is mainly composed of grey matter and nerve cell. In the present paper, the in situ Raman spectra of the cerebral cortex of the birth, teenage and aged monkeys were achieved for the first time. The results show that the Raman spectra for the different age monkey cerebral cortex exhibit most obvious changes in the regions of 1000-1400 and 2800-3000 cm(-1). With monkey growing up, the relative intensities of the Raman bands at 1313 and 2885 cm(-1) mainly assigned to CH2 chain vibrational mode of lipid become stronger and stronger whereas the relative intensities of the Raman bands at 1338 and 2932 cm( 1) mainly assigned to CH3 chain vibrational mode of protein become weaker and weaker. In addition, the two new Raman bands at 1296 and 2850 cm(-1) are only observed in the aged monkey cerebral cortex, therefore, the two bands can be considered as a character or "marker" to differentiate the caducity degree with monkey growth In order to further explore the changes, the relative intensity ratios of the Raman band at 1313 cm(-1) to that at 1338 cm(-1) and the Raman band at 2885 cm(-1) to that at 2 932 cm(-1), I1313/I1338 and I2885/I2932, which are the lipid-to-protein ratios, are introduced to denote the degree of the lipid content. The results show that the relative intensity ratios increase significantly with monkey growth, namely, the lipid content in the cerebral cortex increases greatly with monkey growth. So, the authors can deduce that the overmuch lipid is an important cause to induce the caducity. Therefore, the results will be a powerful assistance and valuable parameter to study the order of life growth and diagnose diseases. PMID- 20302088 TI - [IR and Raman spectroscopic studies on the derivatives of butylphthalide]. AB - dl-NBP is a potentially beneficial and promising drug for treatment of ischemic stroke with multiple actions that affect different pathophysiologic processes, such as improving microcirculation, decreasing brain infarct volume, regulating energy metabolism, and especially inhibiting platelet aggregation and reducing thrombus formation. However, NBP is limited to use in the clinic by other side effects, such as elevated aminotransferase, abnormal liver function and digestive response. Some derivates of NBP were synthesized with the halides (F, Cl and Br) on the 6-position, and their IR and Raman spectra were measured. They proved the complemental information for deducing their structure. By comparing the spectra of the NBP, the band of disubstituted benzene disappeared in the derivatives, and the band of trisubstituted benzenes were observed. The stretching vibrational band of C--H was detected in the Raman spectra, but was not observed in IR. In the low frequency region, the deformation vibration band of --C--C--C--C was also observed in the Raman spectra. PMID- 20302090 TI - [Application of in situ cryogenic Raman spectroscopy to analysis of fluid inclusions in reservoirs]. AB - Identification of salts is a principal problem for analysis of fluid inclusions in reservoirs. The fluid inclusions from deep natural gas reservoirs in Minfeng sub-sag were analyzed by in situ cryogenic Raman spectroscopy. The type of fluid inclusions was identified by Raman spectroscopy at room temperature. The Raman spectra show that the inclusions contain methane-bearing brine aqueous liquids. The fluid inclusions were analyzed at -180 degrees C by in situ cryogenic Raman spectroscopy. The spectra show that inclusions contain three salts, namely NaCl2, CaCl2 and MgCl2. Sodium chloride is most salt component, coexisting with small calcium chloride and little magnesium chloride. The origin of fluids in inclusions was explained by analysis of the process of sedimentation and diagenesis. The mechanism of diagenesis in reservoirs was also given in this paper. The results of this study indicate that in situ cryogenic Raman spectroscopy is an available method to get the composition of fluid inclusions in reservoirs. Based on the analysis of fluid inclusions in reservoirs by in situ cryogenic Raman spectroscopy with combination of the history of sedimentation and diagenesis, the authors can give important evidence for the type and mechanism of diagenesis in reservoirs. PMID- 20302089 TI - [Adsorption of methylene blue on colloidal silver--a surface-enhanced Raman spectroscopy study combined with density functional theory calculations]. AB - Surface-enhanced Raman spectra of methylene blue (MB) at different concentrations in silver colloid were obtained. The results indicate that the physical adsorption is dominant at high concentration while the chemical adsorption is the main fashion at relatively low concentration; there are different adsorption orientations at different concentration: MB+ molecule is perpendicular to the surface of silver nanoparticle at high concentration and adopts a parallel orientation on the surface of nanoparticle at low concentration. The effect of adsorbing time of MB molecule in Ag colloid was investigated and the adsorption dynamics study shows that the parallel orientation at low concentration does not change with the adsorbing time increasing. Density functional theory (DFT) calculations at the level of B3LYP/6-311+G * (for C, S, N, H)/LANL2DZ (for Ag) were employed to optimize the structures and predict Raman frequencies of MB+ and various MB+ -Ag complexes. The results of experiments and calculations suggest that the silver atom prefers to be bound to N and S atoms in the aromatic ring, and thus two different complexes are formed, i.e., conformer N-Ag and conformer S Ag. Moreover, the Mulliken charge population analysis indicates that N atom in the aromatic ring prefers to interact with Ag than S atom does. Finally, the Raman frequencies observed in the experiments and their vibrational modes were tentatively assigned and discussed. PMID- 20302091 TI - [Investigation of hydrophobic effect on the hydrogen-bond formation of 1,1,3,3 tetramethylurea by Raman methods]. AB - The binary systems of 1,1,3,3-tetramethylurea (TMU) with water, TMU with methanol, TMU with ethanol and N,N-dimethylformamide(DMF) with water were measured by Raman method. With the analysis of the frequency changes of stretching vibration of carboxyl with concentration the authors found that the frequency shift underwent two processes: first, the frequency of stretching vibration of carboxyl down shifts with the increase in hydrogen-bond acceptor concentration; secondly, when the concentration of binary system surpasses a critical value, the wave number remains almost constant, and only the rela tive intensity changes. Through this critical volume ratio, the authors found that the large self-associated water molecule was in volved in the TMU aqueous binary system; while the small self-associated molecule or dimer formation was present in other binary systems. PMID- 20302092 TI - [SERS spectra of serum from rash]. AB - The SERS spectra of serums from the healthy persons and rash patients were measured. In the serum of rash, the band of amide I appeared at 1648 cm(-1), while this peak vanished in healthy serums. The relative intensity of 637 cm(-1) assigned to the gauche conformation of C S increased 23% and the band at 725 cm( 1) corresponding to anti-conformation decreases 60%. These indicate that the structure of the protein has changed in serums from the rash patients. The relative intensity at 1449 cm(-1) assigned to the lipids increased nearly one time. The band at 1099 cm(-1) assigned to the Man-D vanished, indicating that the contents of lipids, glucide and protein increased in rash patients. These results may offer a powerful experiment basis for rash diagnosis and biochemistry mechanism study. The multivariae ura statistical methods of principal component analysis (PCA) were also used to analyze the SERS of the serums from healthy persons and rash patients, it can be seen that the regional distribution of rash is wider than healthy volunteers, showing that these serums can be discriminated by PCA. PMID- 20302093 TI - [Raman spectra of carbon fibers during electrochemical treatment]. AB - Laser Raman spectroscopy was employed to characterize the microstructure variations of polyacrylonitrile-based carbon fibers during electrochemical treatment, and the characteristics of first-order Raman spectra of carbon fibers with different treatment time were investigated in the present paper. The results indicate that the Raman spectra of the carbon fibers can be fitted into four bands, named as D (or D1) band, G band, D2 band and D3 band, respectively. The Raman parameters to characterize surface microstructure variations of carbon fibers mainly include R(I(D2)) / I(G), area ratio of D band and G band), I(D2) / I(G) (area ratio of D2 band and G band), I(D3) / I(G) (area ratio of D3 band and G band), and I(D(S))/ I(G) (area ratio of all the disordered structure and G band). The peak separation between D band and G band becomes large after electrochemical treatment. R increases, which indicates that the surface disordered degree of carbon fibers increases. I(D3) / I(G) increases, which is caused by organic molecules, fragments or functional groups; decreases which is caused by the break of the aliphatic structures. With increasing treatment time, I(D(S)) / I(G) increases continuously, and the change trend of l(D(S)) / I(G) is consistent with that of R value, which can be used to comprehensively explain the variation of the surface structure of carbon fibers. So, the variety rules of the structure of carbon fibers can be investigated by laser Raman spectroscopy during electrochemical treatment. PMID- 20302094 TI - [Investigation on photooxidative degradation of polypropylene/organomontmorillonite nanocomposites]. AB - Photooxidation degradation of polypropylene (PP)/organomontmorillonite (OMMT) nanocomposites was studied under UV irradiation at wavelength 365 nm. The OMMT was dispersed homogeneously in the PP matrix. The structural variation induced by photooxidation was detected by FTIR spectroscopy. It can be seen that the evolution of PP and nanocomposites PP/OMMT on irradiation is an increase in absorbance in the hydroxyl and carbonyl absorption regions. Carbonyl index was used to characterize the rate of photooxidative degradation. At the early stage of irradiation (shorter than 11 hours), the rate of photooxidative degradation of PP/OMMT nanocomposites was much faster than that of pure PP. With the increase in the irradiation time, the rate of photooxidative degradation of PP/OMMT nanocomposites became slower than that of pure PP. On the other hand, the OMMT content can also influence the photooxidative degradation rate. The variation in the photooxidative degradation rate is proposed to originate from the competition between the light shielding effect and accelerating photo-oxidative degradation effect of organomontmorillonite. These two effects play roles in the photooxidation process of PP simultaneously. At the early stage of irradiation, the accelerating photooxidative degradation effect dominates. With the increase in the irradiation time, the active sites such as SiOH, --OH etc and transition metal ions (Fe2+, Fe3+ etc) in the OMMT which can accelerate photooxidation are gradually consumed, and then the light shielding effect may play the main role. The method of curve-fitting was used to characterize the influence of organomontmorillonite on the photooxidative degradation products. Compared with pure PP, the content of products of carboxylic acid and anhydride were found to increase, whereas that of ester decreases in PP/OMMT nanocomposites. PMID- 20302095 TI - [Spectrum recovery method for interferometric data]. AB - The interferometric data acquired by Fourier transform spectrometer was a betweenness which couldn't be used directly. For the successful application of the interferometric data, spectrum recovery processing must be adopted. The conventional method based on inverse Fourier transform was frequently used for spectrum recovery. According to the principle analysis of the interferometric data, the mixing model was induced, and the spectrum recovery method based on the mixing model of the interferometric data was presented. Finally, the computer simulation for these two methods mentioned above was implemented, and the recovered spectra were compared with the standard spectrum. The simulation results indicated that the spectral precision of the new method was better than the conventional method, which provided a new scheme for spectrum recovery. PMID- 20302096 TI - [Preparation of GSH capped CdSe/CdS core-shell QDs and labeling of human T lymphocyte]. AB - Two kinds of L-glutathione capped highly fluorescent CdSe/CdS core-shell quantum dots (QDs) emitting green and orange fluorescence at 350 nm excitation were firstly prepared by an aqueous approach and used as fluorescent labels, to link mouse anti-human CD3 which was expressed on human T-lymphocyte. UV-Vis absorption and fluorescence emission spectra of the as-prepared CdSe/CdS core-shell QDs were studied. Compared with the CdSe QDs, a remarkable enhancement in the emission intensity and a red shift of emission wavelength of CdSe/CdS core-shell QDs was observed for the two kinds of QDs emitting green and orange fluorescence. The TEM results showed that the as prepared CdSe and CdSe/CdS QDs dispersed well in aqueous solution, and their shape was approximately spherical, and the CdSe/CdS QDs nano particles emitting green fluorescence are of about 5 nm in diameter. The two kinds of CdSe/CdS QDs were linked with mouse anti-human CD3 to image human T lymphocyte. The fluorescent microscopical images of human T-lymphocyte labeled with CdSe/CdS QDs-CD3 and FITC-CD3 demonstrated that the fluorescent CdSe/CdS QDs exhibited much better photo stability and brighter fluorescence than FITC, showing a good application potential in the immuno-labeling of cells. PMID- 20302097 TI - [Study on the structure and constituents of polysaccharide from ganoderma lucidum]. AB - Ganoderma lucidum polysaccharides were extracted by boiling water from the fruiting bodies of red ganoderma lucidum, then protein was removed by Sevage reagent, with ethanol precipitation, run water dialysis, centrifugation and freeing-drying. Monosaccharides were acetylated and quantified by external standard, and the polysaccharides the amount of total carbohydrates was determined by phenol-sulfuric acid method. The monosaccharide constituents, structure and Mw distribution were analyzed by UV-Vis, IR, GC, GC-MS and HPSEC with ELSD. The results demonstrated that ganoderma lucidum polysaccharides were beige, the yield was about 2%, and the content > or = 43%. IR spectrometry showed that the structure of ganoderma lucidum polysaccharide was pyranoid glucan with beta-glycosidic bond. The quantitative result of external standards indicated that the monosaccharide constituents were mainly composed of glucose, at about 89% percent, and contained a small amount of D-arabinose, D-xylose, D-mannose and D-galactose. It was a homogeneous polysaccharide with the amorphous structure, attributed to biological macromolecules, its Mw distribution was at 80-2000 Kda, and a primary Mw at 2000 Kda. PMID- 20302098 TI - [Optical and spectral parameters in Ce3+ -doped gadolinium gallium aluminum garnet glass-ceramics]. AB - The crystalline phases of Ce3+ -doped gadolinium gallium aluminum garnet (GGAG) glass-ceramics were investigated by X-ray diffraction, and the fluorescence spectra were recorded under the pumping of blue light-emitting diode (LED) using an integrating sphere of 10-inch in diameter, which connected to a CCD detector. The spectral power distribution of the glass-ceramics was obtained from the measured spectra first, and then the quantum yield was derived based on the photon distribution. The quantum yield of Ce3+ emission in GGAG glass-ceramics is 29.2%, meanwhile, the color coordinates and the correlated color temperature (CCT) of combined white light were proved to be x = 0.319, y = 0.349 and 6086 K, respectively. Although the quantum yield is a little smaller than the value in Ce3+ -doped YAG glass-ceramics, the CCT of the combined white light is much smaller than that in the latter. The optical behavior of GGAG glass-ceramics provides new vision for developing comfortable LED lighting devices. PMID- 20302099 TI - [Preparation, characterization and specific biological labeling of silica coated upconversion fluorescent nanocrystals]. AB - The authors synthesized a kind of upconversion nanocrystals NaYF4:Yb3+, Er3+ via the hydrothermal assisted homogeneous precipitation method, and then the nanocrystal was coated with silica. The SEM image demonstrated that the as prepared samples were uniform in size distribution with ca. 25 nm before and ca. 250 nm after silica coating, respectively. The upconversion spectra and photoluminescence lifetime measurement showed that the silica shell had hardly effect on the properties of fluorescence of the NaYF4:Yb3+, Er3+ nanocrystals. At the same time, the naked eye-visible green upconversion fluorescence pattern was acquired from the as-prepared upconversion nanoparticles in the PBS buffer (2 wt%) excited by 980 nm laser at room temperature. These water-soluble nanoparticles were linked to the antibodies using the coupling reagents glutaraldehyde. The circular dichroism (CD) spectra of antibody and upconversion nanoparticles-antibody conjugates were very similar to each other, indicating that the secondary structure of antibody remained largely intact after the conjugation. Finally, antigen-antibody recognition reaction was performed on the surface of a silicon slide. The immunofluorescence in vitro indicated that the upconversion nanoparticles-antibody bioconjugates had excellent species-specific detection ability with hardly non-specific binding. Based on the present results, it is anticipated that the silica-coated upconversion nanoparticles are suitable for use as biolabeling materials. PMID- 20302100 TI - [Study on quantitative model for suspended sediment concentration in Taihu Lake]. AB - The complicated compositions of Case II waters result in the complex properties of spectral curves. The present paper analyzed the in situ measurements data of spectral curves, and further realized the relationships between the properties of spectral curves and suspended sediment concentration. The study found that the max peak of spectral curves was moving to the direction of shortwavelength as increasing suspended sediment concentration, namely the blue shift of wavelength; the area enclosed by spectral curve and coordinate axis in the range of sensitive bands had preferably linear relationship with the suspended sediment concentration (curve area model); the trapezoidal area model which was an approximation of curve area model could also excellently reflect those relationships, and be greatly suitable for multi-spectral satellite imagery retrieval such as LandSat/TM, MODIS and so on. The inversion results of trapezoidal area model for LandSat/TM imagery on October 27, 2003 in Taihu Lake showed that the suspended sediment concentration ranged from 30 to 80 mg x L(-1), the distribution pattern was higher in the west, south and central lake and lower in the east lake; compared with the in situ measurements in the regions, and the relative error of retrieval model was 6.035%. PMID- 20302101 TI - [Modeling and simulation of effect of optical distortion on the large aperture static imaging spectrometer]. AB - As a new type Fourier transform imaging spectrometry, large aperture static imaging spectrometry (LASIS) has come forth in recent years, which has many advantages such as simple principle, high stability and so on. However, the requirement for the optical system design of LASIS was very harsh. As one of the optical aberrations, optical distortion degrades the data quality acquired by LASIS, consequently limits its applications. According to the analysis of the data acquisition principle of LASIS, the data model with the effect of optical distortion was presented, which could be used for LASIS performance pre evaluation. Finally, the computer simlulation of the data model was achieved with supposed parameters. The simulation results indicated that the relative error more than 5% was induced in the recovery spectrum, and approximate 8 nm spectral line deviation was occurred at the long wavelength region. The results show that the 4% optical distortion was inapplicable for LASIS although it is acceptant for common optical imaging system. PMID- 20302102 TI - [Study on the interaction of L-cysteine dipeptide with DNA]. AB - In the present paper the interaction mechanism and mode of biologically active cysteine dipeptide (Cys-Cys) with DNA was studied by UV-Vis spectrophotometry and fluorescence spectroscopy using ethidium bromide as a fluorescence probe. The results showed that in the buffer solution of Tris-HCl (pH 7.20), at low concentration of Cys-Cys, the ultraviolet spectrum of DNA-Cys-Cys system produced hypochromic effect with increasing the concentration of Cys-Cys. When the concentration of Cys-Cys increased to some high extent, the ultraviolet spectrum of DNA-Cys-Cys system produced hyperchromic effect. Salt-effect experiment showed that the interaction is liable to be affected by the ionic strengths, suggesting the existence of electrostatic binding between Cys-Cys and DNA. The fluorescence of EB-DNA had quenching effect with increasing the concentration of Cys-Cys, and the Stern-Volmer equation indicated that the quenching process was a static one. According to the Lineweaver-Burk equation the binding constant was determined to be 1.640 x 10(4) L x mol(-1). From the above results it can be concluded that the interaction mode of Cys-Cys with DNA was mainly electrostatic binding. These findings could contribute to further investigation on the mechanism of oligopeptides interaction with DNA. PMID- 20302103 TI - [Non-invasive measurement of human hemoglobin concentration by dynamic spectrum method]. AB - For non-invasively measurement of the components of human blood, dynamic spectrum method was used to measure hemoglobin concentration of volunteers for the first time. In-vivo measurements were carried out on 34 healthy volunteers, and their dynamic spectra were collected. To ensure the dynamic spectrum data to be valid, a number of experiments were carried out on the dynamic spectrum data. BP artificial neural network was used to establish the calibration model of subjects' hemoglobin concentration values against dynamic spectrum data. Among 34 swatches, 19 swatches were taken as calibration set and the other 15 as prediction set. For calibration set and prediction set, the correlation coefficient was 0.9831 and 0.9365 respectively. The biggest relative error of prediction is 7.5%, and the average relative error is 3.04%. The accuracy of measurement results can satisfy the demand for clinical application. Measurement results show that the influences of measuring conditions on spectra can be decreased effectively by dynamic spectrum method and this method can be applied to accurate non-invasive measurement of human hemoglobin concentration. It can be a good method for non-invasive blood analysis. PMID- 20302104 TI - [A novel spectral surface plasmon resonance 2-D sensing technique and its applications in DNA microarrays]. AB - The authors have previously proposed a novel refractive index two-dimensional sensing technique named "parallel scan spectral surface plasmon resonance imaging". In the technique, with a line-shaped light illumination, an image acquired with CCD detector could provide both SPR wavelength information and one dimensional spatial distribution, and then provide one-dimensional distribution of refractive index with further calculation. Thus, two-dimensional distribution of refractive index of the entire sensing area can be obtained with one dimensional optical line parallel scan. The technique offers advantages of both high sensitivity and high throughput, and could have potential applications in microarray analysis. In the present paper, the authors improve the data processing methods of the technique. The authors use the refractive index of air as a reference to get over the problem of precision of the incident angle. The authors also sense a manually dotted Legionella pneumophila mip DNA probe array with this technique and prove the feasibility of sensing microarrays by this highly sensitive and label-free technique. The relation between the equivalent refractive indices and the concentrations of the dotted Legionella pneumophila mip DNA probes is obtained, which has important reference value for further study. PMID- 20302105 TI - [Characterization of insoluble polyamide-6,T by MALDI-TOF MS]. AB - Five different sample solvents (trifluoroacetic acid, tetrahydrofuran, formic acid, acetonitrile, 60% acetonitrile /5% trifluoroacetic acid) and two kinds of sample preparation methods were chosen for characterizing the structure, mole mass and mass distribution of insoluble polymer of polyamide-6, T (PA6T) by matrix assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). It was shown that the spectra with wide mole mass and high signal to-noise (S/N) ratio were obtained, when using 60% acetonitrile /5% trifluoroacetic acid as solvent, and solvent sample preparation with one step droplet method was better than non-solvent sample preparation. The main chain structure of PA6T polymerized in ionic liquid was analyzed, which was linear without the presence of cyclic polymer. Three structures of end groups were obtained, carboxyl group or amino group at both ends or carboxyl group at one end and amino group at the other. The mean mole mass and mass distribution were obtained by MALDI-TOF MS and size-exclude chromatography (SEC). It was shown that the mean mole mass by MALDI-TOF MS is lower than that by SEC and the mass distribution was narrower than that by SEC method, which resulted from the default of low mass fraction when calculated by exploring data and high mass fraction hardly detected for the difficulty of ionization. MALDI-TOF MS is a suitable method for the characterization of the structure and mole mass of insoluble poly(aromatic amide). PMID- 20302106 TI - [Relationship between simulated acid rain stress and leaf reflectance]. AB - Acid rain is a worldwide environmental problem. Serious acid rain pollution in subtropical China has constituted a potential threat to the health of the local forest. In the present paper, the changing properties of the chlorophyll concentration and spectral reflectance at the visible wavelengths for the six subtropical broad-leaved tree species leaves under simulated acid rain (SAR) treatment with different pH levels were studied. With the increasing strength of the SAR, the chlorophyll concentrations of the experimental species under pH 2.5 and pH 4.0 treatment were higher than that under pH 5.6; the spectral reflectance at the visible wavelengths for pH 2.5 and pH 4.0 were lower than that for pH 5.6 in general; while there weren't significant differences between pH 2.5 and pH 4.0. After the treatment with different levels of SAR, the differences in spectral reflectance at the visible wavelengths mainly focused around the green peak and red edge on the reflectance curve. The subtropical broad-leaved tree species studied were relatively not sensitive to acid rain stresses; some stronger acid rain may accelerate the growth of the tree species used here to some extent. PMID- 20302107 TI - [New highly phosphorescent heteroleptic tris-cyclometalated iridium (III) complexes: synthesis and photophysical characterization]. AB - New heteroleptic tris-cyclometalated iridium(III) complexes (ppy)2 Ir(LX) (ppy==2 phenylpyridine, LX==Sal (salicylic acid), Msal (4-methylsalicylic acid), FSal(4 trifluoro methyl salicylic acid)) was synthesized and characterized. The molecular structure, photophysical properties and thermal stability were tested and analyzed. The results show that the absorption peaks were located around 270, 370, 450 and 484 nm respectively at room temperature. The two former peaks at 270 and 370 nm should belong to 1pi--pi* transition at ppy and transition from salicylic acid ligands to 2-phenylpyridine; The peaks around 450 and 484 nm can be assigned to the charge transfer transition from Ir to ligand (1MLCT and 3MLCT) and 3pi--pi* transition respectively. The PL emission peaks were located at 520, 522, and 510 nm, respectively. The emission of (ppy), Ir(Sal) and (ppy), Ir (MSal) was mainly ascribed to the radiation transition of triple state 3MLCT, while the emission of (ppy)2 Ir(FSal) was mainly from the radiation transition between Sal and ppy, partly from the radiation transition of single state 1MLCT and triple state 3MLCT. The quantum efficiencies of these complexes were 0.37, 0.33 and 0.29 respectively. The thermal decomposition temperature was from 306 to 328 degrees C. (ppy)2 Ir(LX), being a series of efficient phosphorescent materials with good thermal stability, can be used in the organic electroluminescent devices. PMID- 20302108 TI - [Structural and spectral study of a novel rare-earth and 3-bi-pyridine acid polymer]. AB - A novel zero-dimension coordination polymer Gd2 (In)6 (H2O)4 (1) (In = 3 bipyridine acid) was synthesized under hydrothermal condition. By the analysis of single-crystal X-ray diffraction, the structure of the compound is that two Gd atoms connect with zero-dimension bi- nucleus cluster by the bridged carboxylate of four Ins. Based on the determination of the structure, the 2D correlation FTIR spectra with the perturbations of magnetism and thermal was applied. Under the perturbations of temperature, the vibration of the carboxylate has the very strong response, which is related with the strong coordinating ability of the carboxylate. At the same time, due to the different coordinated mode of the carboxylate with Gd, the response of Gd--O bonds is different under the temperature perturbations. Under the perturbations of magnetism, the vibration of the carboxylate has also the very strong response, which may be related with one negetive charge of the carboxylate. The 2D correlation ultraviolet spectral with the perturbation of magnetism were investigated. Compared with one-dimension ultraviolet spectral, the transition of the pi electrons in bi-pyridine ring and the charge transition from ligand to the metal have the very strong response. At the same time, the fluorescence spectral and TGA were studied. PMID- 20302109 TI - [Effect of sand-stabilization engineering on soil humus and components by analysis by several spectroscopy methods]. AB - After the potassium bichromate-strong sulfuric acid hot process, the ultraviolet spectrophotometer was used on the contrast with the traditional titrimetric method to analyze soil (51 years, 43 year, 32 year, 20 year vegetations restores in the Tenggeli sand) humus and the humus components content. At the same time, the infrared spectrum was used to discuss their structure change during restoring process. The result indicated that using the visible spectroscopy method for the determination of the humus and the humus component is feasible. The spectroscopy method determination of organic matter is better (coefficient of variation at most is 7.26%) than the traditional titrimetric method, as it is accurate, fast and simple, and favors large quantities. The result indicated that humus content presents increasing tendency along with restoring ages. Change is big in early restore time, and tends to be stable in the later period. Infrared spectrum shape is similar, but the characteristic peak intensity has obvious difference. Compared with the wind-drift sand, little molecule saccharides decrease and aryl groups increase. PMID- 20302110 TI - [Monitoring stripe rust of winter wheat using PHI based on sensitive bands]. AB - Forty six points representing different severity degree of stripe rust were established in winter wheat field. The canopy reflectance was collected by an ASD hand-held spectrometer at each point. Meanwhile, the diseases index was investigated. These data were used for the following analysis. Firstly, the relationships between diseases index and reflectance of bands in the range of 300 1500 nm were analyzed. The sensitive bands were selected for stripe rust detecting. Secondly, considering the character of PHI image, red bands (620-718 nm) and near infrared bands (770-805 nm) were assigned as the best bands. Finally, the mean reflectance of red bands (620-718 nm) and near infrared bands (770-805 nm) was calculated respectively to construct the reverse model with the observed diseases indexes: DI = 19.241 R1 - 2.20667 R2 + 12.2744. With this model, the severity degree of stripe rust of winter wheat was monitored successfully in PHI image. PMID- 20302111 TI - [Study of building quantitative analysis model for chlorophyll in winter wheat with reflective spectrum using MSC-ANN algorithm]. AB - Preprocess method of multiplicative scatter correction (MSC) was used to reject noises in the original spectra produced by the environmental physical factor effectively, then the principal components of near-infrared spectroscopy were calculated by nonlinear iterative partial least squares (NIPALS) before building the back propagation artificial neural networks method (BP-ANN), and the numbers of principal components were calculated by the method of cross validation. The calculated principal components were used as the inputs of the artificial neural networks model, and the artificial neural networks model was used to find the relation between chlorophyll in winter wheat and reflective spectrum, which can predict the content of chlorophyll in winter wheat. The correlation coefficient (r) of calibration set was 0.9604, while the standard deviation (SD) and relative standard deviation (RSD) was 0.187 and 5.18% respectively. The correlation coefficient (r) of predicted set was 0.9600, and the standard deviation (SD) and relative standard deviation (RSD) was 0.145 and 4.21% respectively. It means that the MSC-ANN algorithm can reject noises in the original spectra produced by the environmental physical factor effectively and set up an exact model to predict the contents of chlorophyll in living leaves veraciously to replace the classical method and meet the needs of fast analysis of agricultural products. PMID- 20302112 TI - [The spectral characteristics and chlorophyll content at winter wheat growth stages]. AB - The canopy spectral reflectance and chlorophyll content of winter wheat were measured and analyzed in the whole growing season. The characteristics of canopy spectral reflectance indicated that the canopy spectral reflectance changed signifi cantly at different stages. It decreased first and increased later with growth progress in the visible region (400-750 nm) after jointing stage, then the reflectance was lowest at booting stage. In near-infrared region (750-1000 nm) the spectral reflectance climbed sharply. The canopy reflectance was declined at booting stage and rose to the highest point at flowering stage. It dropped to minimum level subsequently at milk-ripe stage. However, the spectral reflectance characteristics at jointing stage and booting stage were used to detect the chlorophyll content. High correlation was observed between the canopy spectral reflectance and chlorophyll content. The positive correlation of canopy spectral reflectance with chlorophyll content was found at jointing stage and booting stage. Because the plant spectral reflectance was effected by chlorophyll greatly in visible region, the correlation coefficient reached 0.89 at 552 nm in booting stage. On the contrary, there was a negative correlation at flowering stage. Meanwhile, the red edge inflection point as one of the most important spectral parameters was analyzed at winter wheat growth stages based on the first derivative of reflectance spectra. The relation between the red edge inflection point and chlorophyll content was observed in each plot and the analysis results illustrated that the red edge inflection points could help detect the chlorophyll content at jointing stage and booting stage. The linear model of chlorophyll content with red edge inflection points was built at jointing stage (R2 = 0.92). High correlation was found between thered edge inflection point and chlorophyll content at booting stage. It was showed that the binomial model (R2 = 0.91) was better than linear model (R2 = 0.73). It was indicated that using spectral analysis to detect the winter wheat chlorophyll content non-destructively was feasible. The obtained conclusions also provided theoretical basis for further researches on measuring methods of chlorophyll content in the field. PMID- 20302113 TI - [Retrieval model for subtle variation of contamination stressed maize chlorophyll using hyperspectral data]. AB - Chlorophyll content is an important indicator of photosynthesis activity, stress and nutritional state. In the present paper, the hyperspectral data, foliar chlorophyll content and heavy metal contents in foliar and soil were measured for the maize growing in three natural fields. In most previous research, the contamination stress was controlled artificially in laboratory by adding chromium, zinc or copper pollutant etc. to the soil, and the pollutant concentration added was much higher than that in natural environment. The three sample fields were under different heavy mental contamination level, but all located at the Changchun region, Northeast China, where is called Golden Maize Belts in the world. After continuum removal (400-800 nm), ten spectral indices were computed including max absorption position, normalized reflectance at max absorption position, absorption depth, green peak, normalized reflectance at green peak, red edge, normalized reflectance at red edge, red peak, absorption width, and asymmetry degree. The physics meaning of the above indices and their correlation with maize foliar chlorophyll content were analyzed. It was found that there were close relationships between these indices and foliar chlorophyll content except max absorption position, green edge and asymmetry degree. Besides the asymmetry degree, five indices were selected in the stepwise multiple linear regression for estimating chlorophyll content and its determination coefficient (R2) is 0.7027. Furthermore, in order to measure the weak change information of foliar chlorophyll content under the contamination stress, the BP artificial neural network (ANN-BP) was used. Several ANN-BP models were built and tried with different structure, namely five nodes, seven nodes or ten nodes in input layer, one hidden layer or two hidden layer, and different nodes number in hidden layers. It was found that the highest accuracy of estimates was obtained by the model with two hidden layers, ten nodes in input layer, seven nodes in first hidden layer and 4 nodes in second hidden layer (R2 = 0.9758). PMID- 20302114 TI - [Detection of the expression of transgene in rice plant based on hyperspectral remote sensing technique]. AB - The present study aims to identify the expression of transgene in given rice plant samples in certain conditions. To avoid external noise caused by temperature change and water-loss, field spectrum was collected with ASD field spectrometer in natural state. The study calculated the mean spectrum of samples as main data set analyzed which were controlled by inner clustering coefficient to ensure data quality. By mean spectrum, the noise from random distinctions in few individual cultivators, which could not be expressed in the class stably, could be weakened even with filtering. With the help of parameters, such as red edge and green peak, this study gave qualitative spectral differences between transgenic samples and their parents. The results show that the transgenes in rice plant were expressed and influenced the samples. Moreover, it was found that the parameters of area are more suitable for describing the differences/changes of the samples, while PRI and SR-PRI are more sensitive to indicate them. Most of the above results could be found on the continuum-removal spectrum curve of samples. These conclusive results demonstrate that hyperspectral remote sensing technique has good prospects and application potential in transgene expression detection and monitoring, especially in plant breeding process. PMID- 20302115 TI - [Effects of pulsed electric fields on phenols and colour in young red wine]. AB - The effects of pulsed electric fields (PEFs) applied on the 2 phenolic acids and 3 flavan-3-ols in young red wine, as well as the changes in colour intensity and colour hue, were investigated using a parallel treatment chamber. High performance liquid chromatography (HPLC) coupled with UV-visible detector was used to analyze the contents of these two phenols. The high voltage pulse generator in this experiment designed and produced by Tsinghua University can generate exponential decay pulses. The chambers of this experiment were parallel plate treatment chambers with interelectrode distances of 0.5 cm. The experimental results show that after PEF treatment (energy density: 24.5, 40.5, 60.5 J x mL(-1)) the concentration of most phenolic compounds changed significantly. Moreover, the energy density of 60. 5 J x mL(-1) was chosen as the optimal parameter. PMID- 20302116 TI - [Nitrogen content testing and diagnosing of cucumber leaves based on multispectral imagines]. AB - Using CCD camera and special filters, the growth parameters of cucumber plants, the nitrogen content and the area of leaves, were investigated in an experimental greenhouse. In order to make nutrient stress to the plants, different nitrogen levels were prepared. The basic nitrogen content was 0.067 kg x L(-1) and four different levels of nitrogen contents were made to be 2, 1, 0.5, and 0.2 N, respectively. The genetic and water-segment methods were used to separate IR and R2 images from the background. It was found that the result of water-segment is better. It has clearer boundary, less noise and closer result to the original image. After the reflectance information of cucumber leaves was obtained, the vegetation indexes, RVI, NDVI and GNDVI, were calculated and then the correlation coefficients between each vegetation index and nitrogen content or leave area were analyzed. The result shows that there is an obvious linear correlation between NDVI and nitrogen content of leaves or leave area and the R2 are 0.8209 and 0.7017, respectively. The high correlations were also observed between GNDVI and nitrogen content of leaves or leave area, and the R2 are 0.7625 and 0.6762, respectively. The reason is that the reflectance of IR is mainly affected by reflectivity and the canopy structure of cucumber leaves. As biomass and area of leaves increase with the nitrogen content, the reflectivity of leaves becomes stronger. And the gap among cells of high nitrogen content leaves is large. Cell wall has more water, which has a strong effect on the reflectivity of NIR At visible wavelength, the reflectance of cucumber leaves decreases as nitrogen content increases since the chlorophyll content increases as nitrogen content increases. The trend of correlation between RVI and nitrogen content disagreed with that of the correlation between RVI and leave area. There is an obvious linear correlation between RVI and leave area, and the R2 is 0.8577. However, the correlations between RVI and nitrogen content exhibit a nonlinear relationship, and R2 is only 0.5988. It is because as cucumbers grow older, the reflectance of canopy increases at visible wavelength but decreases at near infrared wavelength. The experimental result proves that CCD camera and special filters can be used as a good method for diagnosing nitrogen content of cucumber plants. PMID- 20302117 TI - [Leaf characteristics extraction of rice under potassium stress based on static scan and spectral segmentation technique]. AB - The timing, convenient and reliable method of diagnosing and monitoring crop nutrition is the foundation of scientific fertilization management. However, this expectation cannot be fulfilled by traditional methods, which always need excessively work on sampling, detection and analysis and even exhibit lagging timing. In the present study, stable images for potassium-stressed leaf were acquired using stationary scanning, and object-oriented segmentation technique was adopted to produce image objects. Afterwards, nearest neighbor classifier integrated the spectral, shape and topologic information of image objects to precisely identify characteristics of potassium-stressed features. Diagnosing with image, the 3rd expanded leaves are superior to the 1st expanded leaves. In order to assess the result, 250 random samples and an error matrix were applied to undertake the accuracy assessment of identification. The results showed that the overall accuracy and kappa coefficient was 96.00% and 0.9453 respectively. The study offered an information extraction method for quantitative diagnosis of rice under potassium stress. PMID- 20302118 TI - [DNA nanosensor fluorescence imaging microscopy]. AB - Quantum dots have many excellent optical properties such as high quantum yield, long fluorescence lifetime, wide excitation spectrum and narrow emission spectrum, tunable emission wavelength and so on, thus have become a newpopular type of fluorescence probes in these years. Quantum-dot-based DNA nanosensor comprising streptavidin-conjugated quantum dots, capture probes with biotin and reporter probes with Cy5 was designed to detect DNA or RNA segments. Capture probes and reporter probes were connected by the target DNA or RNA segments so that quantum dots and Cy5s could be together and FRET (fluorescence resonance energy transfer) could be detected. In the present work, quantum-dot-based DNA nanosensor was combined with ICCD fluorescence microscopy imaging system through the authors' experiments. Using the total internal reflection fluorescence (TIRF), FRET between quantum dots and Cy5s was recorded by ICCD showing that segments of singlestranded target DNA with 30-base length were detected in solution using DNA nanosensor. When Cy5-ssDNA-Biotins were added into streptavi din-conjugated quantum dots in solution, by real time recording, the FRET efficiency was found to increase with time, which indicated the process of streptavidin-conjugated quantum dots capturing Cy5-ssDNA-Biotins. It was also observed that streptavidin-conjugated quantum dots and Cy5-ssDNA-Biotins could both enter living Chinese hamster ovary cells and have FRET. The process of streptavidin-conjugated quantum dots capturing Cy5-ssDNA-Biotins was detected in the cells as well and Cy5s were photobleached after a long time of irradiation. It has been proved that detecting DNA or RNA segments in living cells with DNA nanosensor is possible. PMID- 20302119 TI - [Synthesis of the CaCO3:Eu3+ red phosphor by microwave method]. AB - The red phosphor of CaCO3 doped with Eu3+ was synthesized with the microwave method in the aqueous solution and characterized with electron microscope (SEM), X-ray diffraction (XRD), and photoluminescence and photoluminescence excitation (PL-PLE) spectrum. Also under investigation was the influence of microwave power on luminescence properties. The results showed that the synthesized CaCO3:Eu+ particles were the mixture of various particles in the forms of vaterite with flower-flake, calcite with cubic shape and aragonite with needle-like, which were evenly dispersed. The Eu3+ ion as the luminescent center inhabited the site of Ca3+ in mixed phases of CaCO3:Eu3+. This feature was mainly characterized by the intense charge transfer band range from 200 to 300 nm in the PLE spectrum, which was the wide band excitation. Moreover, the narrow excitation peaks at 319, 395, 465, 535 nm and so on could be detected in the PLE spectrum. For the mixed phase, the magnetic-dipole transition (5)D0 to (7)F1 emission was split into two sublevels at about 589 and 593 nm by the crystal field. The mainly emission peaks were located in the vicinity of 614 and 620 nm, corresponding to the electric dipole transition (1)D0-->(7)F2 of Eu3+ ions that was the pure red emission. Moreover, with the improvement of the microwave power, the emission intensity was on rise for the morphology and phase of the sample changed from the flower-flake vaterite to the needle-like aragonite, coupled with the intensity of red light emission. PMID- 20302120 TI - [Technology of advanced glycation endproducts fluorescence measurement and precorrection]. AB - The necessity to measure advanced glycation endproducts (AGE) was analyzed in the present paper, and the apparatus for measuring skin autofluorescence was also designed making use of the special excitation spectrum and emission spectrum. A portion of tissue at the volar side of the arm of individuals (11 diabetes and 19 control subjects) was illuminated with excitation light, i.e., monochromatic light around 370 nm, and the emission spectrum was detected on the skin of control subjects and diabetic patients respectively. All measurements were performed at room temperature in a semi-dark environment. It can be seen that different sites of an individual could lead to different results, and the color can also affect the results. The technology of fluorescence precorrection was applied in order to get rid of the influence of noise, different site of skin, the color of skin etc. The result indicates that the technology of precorrection is of avail and the repetitiveness is well. PMID- 20302121 TI - [Study of the fluorescence characteristics of DOM from the Yangtze River and Jialing River around Chongqing's urban areas]. AB - The fluorescence emission and excitation emission matrix (EEM) technologies were used to characterize the dissolved organic matter (DOM) in the water body of the Yangtze River and Jialing River around the Chongqing urban areas from April to August 2008. Concerning about the accidents of the Wenchuan's Earthquake in May and Tangjiashan Yansaihu's effects in June, and the high water period time in the summer in two months of July and August, from the EEM obtained from each sampling station and time, the composition, distribution and their changing features of the DOM in the two rivers were investigated as combined with the water samples' environmental parameters such as pH, DO, DOC with EEM's fingerprint features, f(450/500) etc; finally the bio-environment behavior effects of the three types of fluorescence peaks were elaborated, where humic-like, fulvic-like, and protein like from the five sampling stations' EEMs during the five months were given detailed representation. From the experimental results obtained, the fluorescence peaks are mainly composed of two types of fluorophores: humic-like and protein like in the two rivers around the Chongqing urban areas during the investigation in five months, the protein-like's peaks value in Jialing River is higher than the values in the Yangtze River, and all the fluorescence peaks in the two Rivers' water body decrease more or less after the two Rivers join in Chun Tan sampling station; the protein-like peak is notably higher after the "5 x 12" earthquake period time including May and June and high water period time, which mainly originated from terrestrial sources, but its intensities decreased observably while the water bodies of the two rivers joining together in the Chao Tianmen and Chun Tan's sampling station. PMID- 20302122 TI - [Quantitative determination of melamine by fluorescence spectroscopy and radial basis function neural networks]. AB - Based on the experimental study, it was found that melamine solution excited by UV light can generate a strong fluorescence. The fluorescence spectrum is within a range from 310 to 600 nm, the peak wavelength of the fluorescence is about 420 nm, and the relationship between fluorescence intensity and melamine solution concentration is nonlinear. A method for the determination of melamine solution concentration was presented, which was based on fluorescence spectroscopy and radial basis function neural networks. For each sample, 30 emission wavelength values were selected, the fluorescence intensity corresponding to the selected wavelength was used as the network data, and a radial basis function neural network was trained and constructed. The trained radial basis function neural network was employed to predict the melamine solution concentration in five kinds of samples, and the relative errors of the results were 0.93%, 0.09%, 0.31%, 1.55% and 4.61%, respectively. The results show that this method can determine the content of melamine quickly and accurately. The whole research outcomes will provide a new method for determining the content of melamine and food safety supervision. PMID- 20302123 TI - [Application of three-dimensional fluorescence spectra technique to discrimination of distilled spirits based on support vector machines]. AB - In order to study the identifying and classification method of distilled spirits, about 100 kinds of normative distilled spirits were selected as the laboratory samples and their fluorescence spectra induced by ultraviolet light were measured by Roper-Scientific SP-2558 respectively. Then, using the statistics and plot software Origin 7.5, the authors composed the three-dimensional fluorescence spectra of the distilled spirits. In the meanwhile, the three-dimensional fluorescence spectra of the dis tilled spirits were also studied respectively. The authros compared the three-dimensional fluorescence spectra of different distilled spirits with the same brands and that of different spirits with the same brands. The authors are very confident that there must be some typical parameters, by which the authors can distinguish different kinds of distilled spirits with different brands effectively. And the authors found that while the three-dimensional fluorescence spectra of different distilled spirits with different brands are definitely different by their three typical parameters including the number of the major summit, position of the major summit and optimum wavelength, the three typical parameters of the three-dimensional fluorescence spectra of different distilled spirits with the same brand are very similar. Finally, the authors extracted the three typical parameters that are the number of the major summit, position of the major summit and optimum wavelength. Then, the data were processed by computer for emulation. As a result, the authors found that, using the three characteristic parameters, different kinds of distilled spirits can be classified ac curately by the algorithm of LS-SVM (least squares support vector machine). The outcomes of the data emulated by different algorithms were obtained seriatim. The authors compared the outcomes, and the fact proved that more accurate outcome of identifying and classification can be obtained by LS-SVM. PMID- 20302124 TI - [Rapid method for determination of furfural and 5-hydroxymethyl furfural in pre extraction stream of biomass using UV spectroscopy]. AB - The present paper reports a rapid method for the determination of furfural (F) and 5-hydroxymethyl furfural (HMF) in pre-extraction liquors of lignocellulosic biomass based on UV spectroscopy. In a concentrated acetic acid medium, F and HMF have an isosbestic point at 276 nm. It was found that the acidic soluble lignin in the pre-extraction sample is the major interference species in the F and HMF spectroscopic quantification However, only acidic soluble lignins have the absorption at the wavelengths above 325 nm. Based on the absorption of the acidic soluble lignins at 325 nm, their absorptions at either F or HMF absorbed wavelengths can be determined. Thus, with a simple triple-wavelength technique, both F and HMF in the pre-extraction liquors of lignocellulosic biomass can be quantified based on the spectroscopic measurement at the isosbestic point wavelength (276 nm), maximum absorption wavelength of F (272 nm) and the acid soluble lignin absorbed wavelength (325 nm). The present method does not require the hazardous organic compounds (such as phenolic compounds etc.) acting as a color reagent in the experiment. It is not only simple and rapid, but also has a good measurement precision and accuracy, with the relative standard deviations of 3.02% and 2.72%, and recoveries of 95%-107% and 96%-101%, respectively, in the F and HMF quantification. The present method is suitable for use in the research on pre-extraction hemicellulose of the lignocellulosic biomass in bio-refinery area in order to achieve a high selective sugar conversion. PMID- 20302125 TI - [Qualitative and quantitative analysis of various elements in chromite ore by ICP AES]. AB - Kind of the elements in chromite ore was firstly determined by ICP-AES. Twenty nine elements, such as Cr, Fe, Al, Mg, Zn, Ca and Ni, were contained in the chromite sample based on the qualitative analysis. Then the contents of main elements Cr, Fe, Al, Mg, Ca, T, Si, Mn and V were measured. The chromite samples processing procedures have two steps, the first is decomposition by nitrate carbonate and sodium tetraborate at 950 degrees C for 30 min, then leaching by dilute hydrochloric acid at 80 degrees C for 10 min. The method showed satisfactory precision and accuracy with the RSDs between 0.48% and 2.05% and the recovery rates between 90.5% and 111.3%. PMID- 20302126 TI - [Determination of metal elements in paper sludges by ICP-AES]. AB - Metal elements, especially the heavy metal element, need to be considered for resource utilization of paper sludge. Seventeen kinds of metal elements were determined by ICP-AES method, which were form two kinds of paper sludge from Anhui Shanying paper mill, one kind of paper sludge from Fujian Qingshan paper mill, and one kind of paper sludge from Fujian Zhongzhu paper mill. The results show that there are different amounts of metal elements in the 4 kinds of paper sludge including poisonous metal elements, such as Cr, etc, metal element which is poisonous when excessive, such as Fe, etc, and P and K which are beneficial for plant growth Al and Ca contents are maximal. The recovery ratio for Fujian Zhongzhu paper mill obtained by standard addition method is 94.4%-107.3%. Heavy metal elements content lower than the national standard GB/4284-84 "Control standards for pollutions in sludge form agricultural use". The order of heavy metal elements content is paper sludge from Fujian Zhongzhu paper mill0.05) and between BS and RTL (R2= 0.038) was observed. The results suggested that there was no significant correlation between the HLT and RTL with the BS of the self-etching adhesive to dentin. PMID- 20302217 TI - Observation of tags and hybrid layer of a single bottle conventional adhesive system and a self-etching adhesive system, on sound dentin. AB - This experimental light microscopy study investigated the formation of a hybrid layer and resin tags on sound dentin, after utilization of conventional and self etching adhesive systems. After restorative procedures, the specimens were decalcified in a formic acid and sodium citrate solution, embedded in paraffin, sectioned at 6-microm thickness and stained by the Brown & Brenn method for analysis and measurement by light microscopy (AXIOPHOT) (400x). The results were statistically analyzed by analysis of variance, at a significance level of 5%. Based on the results, it could be concluded that the conventional adhesive allowed the formation of a thicker hybrid layer than the self-etching adhesive, with similar penetration into the dentinal tubules (resin tags). PMID- 20302218 TI - A comparison of the film thickness of two adhesive luting agents and the effect of thermocycling on their microTBs to feldspathic ceramic. AB - The aim of the present study was to evaluate the effect of thermocycling (TC) on the microtensile bond strength (microTBS) of two luting agents to feldspathic ceramic and to measure their film thickness (FT). For the microTBS test, sixteen blocks (6.4 x 6.4 x 4.8 mm) were fabricated using a feldspathic ceramic, etched with 10% hydrofluoric acid, rinsed and treated with the silane agent. The ceramic blocks were divided into two groups (n= 8): Gr1: dual-cured resin cement and Gr2: flowable resin. The luting agents were applied on the treated surfaces. Microsticks (1 +/-0. 1mm2) were prepared and stored under two conditions: dry, specimens immediately submitted to the microTBS test, and TC (6,000 cycles; 5 degrees C-55 degrees C). The microTBS was evaluated using a universal testing machine (1 mm/min). The microTBS data (MPa) were submitted to two-way ANOVA and Tukey' test (5%). For the FT test (ISO 4049), 0.05 ml of each luting agent (n=8) was pressed between two Mylar-covered glass plates (150 N) for 180 seconds and light polymerized. FT was measured using a digital paquimeter (Model 727-2001). The data (mm) were submitted to one-way ANOVA. The luting cement did not influence the microTBS results (p= 0.4467). Higher microtensile bond values were found after TC (20.5 +/- 8.6 MPa) compared to the dry condition (13.9 +/- 4. 7MPa), for both luting agents. The luting agents presented similar film thicknesses: Gr1- 0.052 +/- 0.016 mm; Gr2-0.041 +/- 0.003 mm. The luting agents presented similar film thickness and microTBS values, in dry and TC conditions and TC increased the bond strength regardless of the luting agent. PMID- 20302219 TI - The effect of smoking on gingival crevicular fluid volume during the treatment of gingivitis. AB - Smoking is detrimental to periodontal tissues, and periodontal destruction is greater among smokers. Paradoxically, smokers seem to have less gingival bleeding than never-smokers with comparable supragingival plaque. There is scarce information about the impact of smoking on gingival crevicular fluid (GCF) volume. This single-arm study clinical trial assessed the effect of smoking on GCF volume during the treatment of gingivitis. The sample included 24 never smokers (47.3 +/-6.7years old, 41.7% males) and 21 smokers (45.8 +/- 5.1 years old; 55% males; 19.6 +/- 11.8 cigarettes/day; 24.1 +/- 8.7 years of smoking) with gingivitis and chronic periodontitis. After baseline supragingival scaling, patients received oral hygiene instructions weekly for 180 days. Particqants were examined at baseline, 30, 90 and 180 days, and gingival bleeding index (GBI), bleeding on prob-ing (BOP), periodontal probing depth (PPD) and GCF volume were recorded. Statistical analysis was performed using linear models (Wald test, p<0.05%). Smokers had significantly smaller GCF volumes than never-smokers. This finding was not attributed to GBI, BOP or PPD. Higher volumes of GCF were significantly associated with deeper pockets. GCF was significantly reduced throughout the study for both smokers and never-smokers, and the largest reductions were seen at 30 days. Smoking affected the GCF crevicular fluid volume independently of the presence of gingival bleeding, BOP and PPD. Smoking status and PPD should be taken into account when GCG volume and components are under investigation. PMID- 20302220 TI - Dye diffusion in instrumented root canals irrigated with different solutions. AB - Success in endodontics depends largely on the activity of the irrigation solutions used during canal cleaning and shaping. Sometimes the irrigation solutions should act deep within the dentin, particularly in cases of chronic infectious lesions, in which it has been found that germs can lodge in the depths of the dentinal tubules. The aim of this study was to compare the penetration of methylene blue in root dentin in instrumented teeth irrigated with different solutions, considering the apical, middle and cervical thirds. Single-rooted teeth were instrumented, irrigated, flooded with 2% methylene blue, washed and cut into thirds. Dye penetration in the dentin was measured by means of two procedures. Linear measurement: maximum dye penetration was recorded towards the four surfaces of each third. Area measurement: the stained surface of each third was measured on digitalized images. On analyzing the data with Friedman and Kruskall Wallis tests, it was found that there was greater penetration of methylene blue in the coronary third in all experimental groups, followed by middle and apical thirds. The mean values for the different groups using the linear method were EDTA 17%: 71.69% - 60.10% - 34.55%. NaOCl 2.5%: 54.04% - 41.79% - 27.53%. CHX 0.2%: 44.28%, 37.58%, 17.80%; and using the area method the mean values were: 17% EDTA: 61.52%, 45.44%, 27.08%. 2.5% NaOCl: 38.15%, 30.77%, 14.60%. 0.2% CHX: 40.95%, 35.46%, 12.27%,for the cervical, middle and coronary thirds respectively. Dye penetration was greatest with 17% EDTA, followed by 2.5% NaOCl and 0.2% CHX, whereas none was observed when distilled water was used. PMID- 20302221 TI - The use of topical subgingival gels of non-steroidal anti-inflammatory drugs (NSAIDs) as an adjunct to non-surgical management of chronic periodontitis. AB - The treatment of chronic periodontitis consists of conventional mechanical debridement and removal of plaque and calculus'. Topical NSAIDs could be used to complement the therapy as an adjunct to resolve the inflammatory process and clinical signs of the disease more rapidly. A randomized clinical trial was performed on 33 systemically healthy patients diagnosed with chronic periodontitis, aged 21 to 40 years. All patients underwent scaling and root planing on one quadrant per week, and sub-gingival gel was applied 48 hours after each session. Patients were grouped into 4 treatment protocols with gels containing: (1) placebo, (2) 1% acetyl-salicylic acid (ASA), (3) 1% ketoprofen (KTP) and (4) 2% ketoprofen. The clinical variables studied were: probing depth, attachment level, tooth mobility, plaque index, gingival index and bleeding on probing. All protocols (groups 1, 2, 3 and 4) induced a reduction of probing depths, plaque and gingival indices and bleeding on probing. The 1% ASA and 2% KTP protocols (groups 2 and 4) significantly reduced the probing depth variable (ANOVA p<0.05). PMID- 20302222 TI - Overjet and overbite analysis during the eruption of the upper permanent incisors. AB - ABSTRACT The purpose of this study was to analyze the overjet and overbite behavior during eruption of the upper permanent incisors. Fourth-eight plaster casts of 16 patients from ages 6-13 years were appraised longitudinally. It was found that the overjet remains constant, starting at the eruption of the upper permanent central incisors until eruption of the upper permanent canine teeth, while the overbite increases after eruption of the upper permanent lateral incisors and remains constant with the eruption of the canine teeth. PMID- 20302223 TI - Effects of thermocycling on mechanical properties of soft lining materials. AB - Soft linings are materials used to reduce the tension and forces of mastication, forming all or part of the fitting surface of a denture. This study evaluated the effect of thermocycling on water absorption, solubility, Shore A hardness and color stability of permanent soft liner materials. MATERIAL AND METHODS: Two chemically activated soft liner materials (Sofreliner S; GC Reline Ultrasoft) were tested. Twenty cylindrical specimens (30.0 x 1.0 mm) were prepared for measuring water absorption and solubility and another twenty (30.0 x 3 mm) for analyzing Shore A hardness and color stability. Color was measured by a spectrophotometer before and after 2000 thermocycles. A one-way ANOVA test and Tukey test at a 5% confidence level (p<0.05) were performed. RESULTS: The results did not show statistical differences for water absorption, solubility or color stability. The post-thermocycling Shore A hardness values were significantly higher than those before the treatment. CONCLUSION: Thermocycling of soft liner materials increased Shore A hardness. PMID- 20302224 TI - Malignant oral-maxillary neoplasm in children and adolescents. A retrospective analysis from the biopsy service at a school of dentistry in Argentina. AB - There are few studies on oral-maxillary lesions in children and adolescents, and reports on malignant neoplasms are scarce. Comparison of available data is difficult due to the different criteria and racial-ethnic origin of the populations in each study. The aim of this work was to perform a retrospective study of malignant oral neoplasms in patients aged up to 20 years diagnosed at a center specialized in histopathological diagnosis of oral diseases between 1990 and 2005. The 24 retrieved cases accounted for 0.9% (n: 2434) of total biopsies in this age group during that period, and for 8.4% (n: 236) of the tumors. Mean age of the whole population was 9.2 years with even distribution according to sex. The most frequent tumor types were extranodal non-Hodgkin lymphoma (7 cases), osteosarcoma (4 cases) and Ewing sarcoma (3 cases). These data can be considered representative of our population of children and adolescents and serve as a basis for recognition and presumptive diagnosis in clinical practice. PMID- 20302225 TI - We all need a net. PMID- 20302226 TI - Mayo Clinic was first. PMID- 20302227 TI - Net work. Minnesota's two largest safety-net hospitals are waging an online campaign to save GAMC. PMID- 20302228 TI - Rural delivery. A new fellowship prepares family physicians to do much-needed obstetrics work in rural communities. PMID- 20302229 TI - Caring collaborative. How residents of one Minnesota county joined forces to provide free medical services. PMID- 20302230 TI - Weighing reform. PMID- 20302231 TI - Community service. PMID- 20302232 TI - Reflections on reform. Fix the bill: a call for future bipartisan health care reform. PMID- 20302233 TI - Reflections on reform. A question of value. PMID- 20302234 TI - Eating an elephant. A sampling of the plateful of proposals in the Senate health care reform bill. PMID- 20302235 TI - A net worth saving. Minnesota's health care safety net is a needed now more than ever. PMID- 20302236 TI - America's safety net and health care reform--what lies ahead? Even if the nation reforms its health care system, we will still need to tend to our tattered safety net. PMID- 20302237 TI - The insurance safety net. Minnesota's public and private programs. AB - More than 725,000 people in Minnesota get their health insurance coverage through safety-net programs.This article describes the four safety-net insurance programs operating in Minnesota--Medical Assistance, MinnesotaCare, General Assistance Medical Care, and the Minnesota Comprehensive Health Association-their eligibility guidelines, coverage limitations, and financing mechanisms. PMID- 20302238 TI - The addicted physician. A rational response to an irrational disease. AB - Physicians are as likely to experience drug and alcohol addiction as anyone in the general population. They are more likely than others, however, to abuse prescription medications. Dealing with an impaired colleague is a difficult, emotionally charged job for physician leaders and hospital administrators, who've often had little training on how to handle such a situation. In addition to describing a case of an addicted physician, this article reviews data about the incidence of addiction among physicians and the challenges associated with confronting such a problem. It also describes the legal reporting requirements and resources such as the Minnesota Health Professionals Services Program and Physicians Serving Physicians that can help physicians get into treatment programs designed specifically for health care professionals. Physicians who go through such treatment programs and subsequent monitoring have been found to have remarkable recovery rates. PMID- 20302239 TI - Forgiveness denied, healing delayed. A young doctor learns that wounds of the "heart" can be as damaging as injuries to the body. PMID- 20302240 TI - A sweet solution? And a major philatelic error. PMID- 20302241 TI - This issue: childhood obesity. PMID- 20302242 TI - A 10-year-old girl being evaluated for cardiomegaly. PMID- 20302243 TI - Treatment of molluscum contagiosum with cantharidin: a practical approach. AB - Molluscum contagiosum is very common. In this article we discuss the use of cantharidin as a treatment option for molluscum contagiosum and give detailed information about distribution sources, how to apply it, and caveats regarding its use.Molluscum contagiosum is a common viral disease of childhood caused by a poxvirus, which presents with small, firm, dome-shaped, umbilicated papules. It is generally benign and self-limited, with spontaneous resolution within 6 months to several years. Watchful waiting can often be an appropriate management strategy; however, some patients either desire or require treatment. Reasons for actively treating molluscum contagiosum may include alleviation of discomfort and itching (particularly in patients where an eczematous eruption - the so-called "molluscum eczema" - is seen in association) or in patients with ongoing atopic dermatitis where more lesions are likely to be present. Other reasons for treatment include limitation of spread to other areas and people, prevention of scarring and superinfection, and elimination of the social stigma of visible lesions. No one treatment is uniformly effective.Treatment options include destructive therapies (curettage, cryotherapy, cantharidin, and keratolytics, among others), immunomodulators (imiquimod, cimetidine, and Candida antigen), and antivirals (cidofovir). In this article we discuss and describe our first-line treatment approach for those molluscum needing treatment - cantharidin. PMID- 20302244 TI - Childhood obesity and the built environment. PMID- 20302245 TI - Metabolic and respiratory comorbidities of childhood obesity. PMID- 20302246 TI - Practical application of the nutrition recommendations for the prevention and treatment of obesity in pediatric primary care. PMID- 20302247 TI - Motivational interviewing (patient-centered counseling) to address childhood obesity. PMID- 20302248 TI - The importance of exercise: know how to say 'go'. PMID- 20302249 TI - Psychological complications of obesity. PMID- 20302251 TI - Embracing technology. PMID- 20302254 TI - Herpes zoster in older adults. AB - Herpes zoster (HZ) is a common condition among older adults, manifested by pain and the classic presentation of a unilateral rash that follows a dermatomal distribution and does not cross the midline of the body. It is caused by reactivation of the virus that caused chickenpox during an earlier infection. In many cases, acute HZ is followed by a severe and disabling complication known as postherpetic neuralgia (PHN), characterized by pain that persists for months or even years after the HZ rash heals. Using an individual example, this article provides information on the clinical manifestations, evidence-based treatment recommendations for, and prevention of HZ and PHN through use of the zoster vaccine Zostavax, licensed in the United States in 2006. PMID- 20302256 TI - The Maisonneuve injury: a comprehensive review. PMID- 20302257 TI - Sharing decisions with patients. PMID- 20302260 TI - Clip & save: drug chart. FDA-approved drugs to treat ADHD. PMID- 20302261 TI - Responding to restraint issues. PMID- 20302262 TI - Occupational therapy should be part of conversion disorder treatment. PMID- 20302265 TI - A closer look at caregiving. PMID- 20302267 TI - How to help when disaster strikes. AB - Nurses aligned with a specific disaster relief system maximize their opportunities to participate "on the ground" when a disaster strikes. Nurses can align with many excellent governmental and nongovernmental organizations in preparation for local, state, national, or international emergency relief responses. This article discusses some of the primary health care-related disaster relief organizations, how to connect with them, and the considerations in preparing for deployment. PMID- 20302266 TI - The professional association and practice excellence. PMID- 20302268 TI - Establishing an incident review committee. AB - A well-defined incident review committee may prevent losses, identify areas for corrective action, and promote overall safety in an organization. A multidisciplinary committee will involve employees in the safety process and heighten safety awareness. Reviewing injuries, incidents, occupational illnesses, and workers' compensation claims assists in root cause analysis and enables an organization to be proactive in preventing further employee incidents and injuries. PMID- 20302269 TI - A biopsychosocial perspective on the management of work-related musculoskeletal disorders. AB - This article provides an overview of current literature about workplace-related musculoskeletal disorders from a biopsychosocial perspective. The authors conclude that disability management and early intervention efforts can only be meaningful within the context of targeted interventions, including mechanisms for psychosocial screening. In addition, they suggest that return to work should be considered an integral, rather than superficial, contribution to the rehabilitative process. PMID- 20302271 TI - Nursing compact. AB - A nursing licensure compact is an agreement between two or more states that the licensing of a nurse in one place will be valid in the other. This is especially critical for the occupational health nurse, who may practice in more than one state. PMID- 20302272 TI - N-aryl chromophore ligands for bright europium luminescence. AB - Sterically hindered N-aryl-benzimidazole pyridine-2-carboxylic acids (aryl = phenyl, 4-biphenyl, 2-naphthyl) readily form homoleptic, neutral, nine-coordinate europium complexes which display efficient sensitized luminescence in solid state and in dichloromethane solution with quantum yields reaching 59% and have monoexponential and nearly temperature-independent lifetimes as long as 2.7 ms. The ligand-centered absorption band with a maximum at 321-342 nm and intensity (50-56) x 10(3) M(-1)cm(-1) ensures efficient harvesting of excitation light by the complexes. Variation of N-aryl chromophore enhances the ligand absorption at 250-350 nm without changing its triplet state energy which amounts to (19.2-21.3) x 10(3) cm(-1). Photophysical properties of europium complexes benefit from adequate protection of the metal by the ligands against non-radiative deactivation and efficient ligand-to-metal energy transfer exceeding 70%. A correlation is observed between the sensitized luminescence quantum yields of europium and the ligand triplet state energy; in certain cases it points to the presence of a second-sphere quenching of Eu(III) by co-crystallized water in the solid state. PMID- 20302273 TI - The importance of precursor and successor complex formation in a bimolecular proton-electron transfer reaction. AB - The transfer of a proton and an electron from the hydroxylamine 1-hydroxyl 2,2,6,6-tetramethylpiperidine (TEMPOH) to [Co(III)(Hbim)(H(2)bim)(2)](2+) (H(2)bim = 2,2'-biimidazoline) has an overall driving force of DeltaG degrees = 3.0 +/- 0.4 kcal mol(-1) and an activation barrier of DeltaG(degrees) = 21.9 +/- 0.2 kcal mol(-1). Kinetic studies implicate a hydrogen-bonded "precursor complex" at high [TEMPOH], prior to proton-electron (hydrogen-atom) transfer. In the reverse direction, [Co(II)(H(2)bim)(3)](2+) + TEMPO, a similar "successor complex" was not observed, but upper and lower limits on its formation have been estimated. The energetics of formation of these encounter complexes are the dominant contributors to the overall energetics in this system: DeltaG degrees ' for the proton-electron transfer step is only -0.3 +/- 0.9 kcal mol(-1). Thus, formation of the precursor and successor complexes can be a significant component of the thermochemistry for intermolecular proton-electron transfer, particularly in the low-driving-force regime, and should be included in quantitative analyses. PMID- 20302274 TI - Synthesis, structure, and two-photon absorption studies of a phosphorus-based tris hydrazone ligand (S)P[N(Me)N=CH-C6H3-2-OH-4-N(CH2CH3)2]3 and its metal complexes. AB - A phosphorus-supported multidentate ligand (S)P[N(Me)N=CH-C(6)H(3)-2-OH-4-N(CH (2)CH(3))(2)](3) (1) has been used to prepare mononuclear complexes LM [M = Fe (2) Co (3)] and trinuclear complexes L(2)M(3) [M = Mn (4), Ni (5), Zn (6), Mg (7), Cd (8)]. In both 2 and 3 the ligand binds the metal ion in a facial coordination mode utilizing three imino nitrogen (3N) and three phenolic oxygen (3O) atoms. The molecular structures of L(2)Mn(3), L(2)Ni(3), L(2)Zn(3), L(2)Mg(3), and L(2)Cd(3) (4-8) are similar; two trihydrazone ligands are involved in coordination to hold the three metal ions in a linear fashion. Each of the trishydrazone ligands behaves as a trianionic hexadentate ligand providing three imino and three phenolic oxygen atoms for coordination to the metal ions. The coordination environment around the two terminal metal ions is similar (3N, 3O) while the central metal ion has a 6O coordination environment. Third-order non linear optical properties of these compounds as measured by their two-photon absorption (TPA) cross section reveals that while 1 does not possess obvious TPA activity, complexes 2 (3213 GM) and 4 (3516 GM) possess a large TPA cross section at 770 nm. PMID- 20302275 TI - Photovoltaic devices with an active layer from a stamping transfer technique: single layer versus double layer. AB - In this study, organic photovoltaic devices with single or double-layered active film were prepared from a stamping transfer technique. A P3HT/PCBM single-layered active layer and a ratio-controlled P3HT/PCBM double-layered active can be successfully fabricated with the help of ultraviolet curable polycarbonate films via a stamping transfer technique. The maximum conversion efficiency values 2.85 for a single active layer transferred device and 3.24% for an optimized double active layer transferred device. Even though transferred double layers should have a sharp interface boundary, an intermixed zone with a concentration gradient was generated by the interpenetration of a donor-rich layer and an acceptor-rich layer in a thermal annealing process. The generation of the intermixed zone is confirmed by Auger electron spectroscopy. The enhanced conversion efficiency levels are attributed to the increased efficiency of the carrier transporting process, which is due to the fact that the concentration gradient is combined with the efficient charge generation from the bulk heterojunction layers. PMID- 20302276 TI - Relating interactions of dye molecules with chitosan to adsorption kinetic data. AB - The scope of the present work is the study of the adsorption behavior of two dyes of different nature/class on several chitosan derivatives. The adsorbents used were grafted with different functional groups (carboxyl, amido, sulfonate, N vinylimidazole) to increase their adsorption capacity and cross-linked to improve their mechanical resistance. This complete kinetic analysis was realized at 25, 45, and 65 degrees C to observe the effect of temperature on adsorption rates for each adsorbent-adsorbate system. Activated carbon was also used as an adsorbent for reference/comparison. The experimental equilibrium data were successfully fitted to the Langmuir-Freundlich (L-F) isotherms, presenting high correlation coefficients (R(2) approximately 0.998). A detailed pore-surface diffusion with local adsorption-desorption model has been developed to describe the adsorption kinetics in chitosan adsorbents. The existence of kinetic data in several temperatures assists in recognizing the diffusion mechanism in the adsorbent particles. The findings on diffusion mechanisms and the corresponding coefficients, from using the model to match the experimental data, are compatible with the expected adsorbent-dye interactions based on their chemical structure. PMID- 20302277 TI - One-step dry method for the synthesis of supported single-crystalline organic nanowires formed by pi-conjugated molecules. AB - We present for the first time a general vacuum process for the growth of supported organic nanowires formed by pi-conjugated molecules, including metalloporphyrins, metallophthalocyanines, and perylenes. This methodology consists on a one-step physical vapor deposition of the pi-conjugated molecules. The synthesis is carried out at controlled temperature on substrates with tailor morphology which allows the growth of organic nanowires in the form of squared nanofibers and nanobelts. The study of the nanowires by electron diffraction and HRTEM combining with the results of a theoretical analysis of the possible arrangement of the pi-conjugated molecules along the nanowires reveals that the nanowires show a columnar structure along the fiber axis consisting of pi-stacked molecules having a herringbone-like arrangement. The formation of these nanowires on different substrates demonstrates that the growth mechanism is independent of the substrate chemical composition. An in-depth phenomenological study of the formation of the nanowires drives us to propose a growth mechanism based on a crystallization process. Furthermore, the growth method allows the fabrication of two particular 1D heterostructures: binary and open core@shell organic nanofibers. PMID- 20302278 TI - Role of solubilized water in micelles formed by Triton X-100 in 1-butyl-3 methylimidazolium ionic liquids. AB - We demonstrate here the aggregation behavior of a nonionic surfactant Triton X 100 in two 1-butyl-3-methylimidazolium ionic liquids (the hydrophilic IL [bmim][BF(4)] and the hydrophobic IL [bmim][PF(6)]) by surface tension measurements. The effects of added water on the microstructure of Triton X-100 in ILs micelles are investigated. When small amounts of water are added to Triton X 100 in [bmim][PF(6)] micelles, the water molecules are first bound to the ethylene oxide (EO) units of Triton X-100 and then form the water pool in the core of the microemulsion. When water molecules are added to the Triton X-100 in [bmim][BF(4)] micelles, there is no microemulsion formed; these water molecules are first solubilized in [bmim][BF(4)]. When the solubilization is saturated, the water molecules start to bind to the EO group of Triton X-100; these results are confirmed by UV-vis, FTIR, and (1)H NMR spectra. PMID- 20302279 TI - Rupture mechanism of aromatic systems from graphite probed with molecular dynamics simulations. AB - Intermolecular interactions involving aromatic rings are of pivotal importance in many areas of chemistry, biology and materials science. Mimicking recent atomic force microscopy (AFM) experiments that measured the adhesion forces of single pi pi complexes, here interactions between pyrene/coronene and graphite have been probed by force-probe molecular dynamics (FPMD) simulations. The pyrene or coronene molecule was connected to a virtual spring through a flexible poly(ethylene glycol) (PEG) linker and was pulled away from graphite in water under constant velocity. Pyrene and coronene showed similar unbinding pathways featuring four states, with a transition and an intermediate state connecting the bound and unbound states in terms of distance and interplanar angles. Transient conformations with tilted orientations (approximately 40 degrees) and with one side of the aromatic structure still in contact with the graphite surface (approximately 70 degrees) were identified as the transition and intermediate states, respectively, similar to previously observed perpendicularly stacked benzene dimers. The distance to transition state x(tr) was determined to be 0.23 +/- 0.03 nm both for pyrene/graphite and coronene/graphite. The complexes share similar unbinding pathways, but coronene binds to graphite more strongly than to pyrene. PMID- 20302281 TI - Orientation controlled Schottky barrier formation at Au nanoparticle-SrTiO3 interfaces. AB - In this paper, the electrical transport of Au nanoparticle/SrTiO(3) nanointerfaces has been studied. The fabrication method detailed creates atomically smooth SrTiO(3) substrate and controlled Au nanoparticle morphologies to create two unique interfaces. The two interfaces are identifiable in atomic force microscope images allowing us to compare variations in the electronic structure using scanning force spectroscopy. By combining AC imaging with scanning force spectroscopy, the interfaces are effectively probed and left undisturbed. The ideality factor and Schottky barrier height are obtained and compared with one orientation exhibiting deviations from thermionic emission theory while the other showing strong similarities to large area Schottky contacts. It is thus shown that controlling the interface structure is of utmost importance to controlling nanoscale Schottky barriers. PMID- 20302280 TI - Quantitative spreading kinetics of a three molecular layer liquid patch. AB - The late stage kinetics of the spreading of a smectic nanodrop on a solid surface was investigated by direct and real time imaging of a three molecular layer patch using the SEEC microscopy. Experimental data do not conform to the only available theory, which covers only weakly stratified liquids. A new model is proposed, in remarkable agreement with experiments, in which the spreading mechanism appears to be a quasi-static process ruled by solid/liquid interactions, 2D Laplace pressure, and separate edge and surface permeation coefficients. PMID- 20302282 TI - Highly stereoselective 7-endo-trig/ring contraction cascade to construct pyrrolo[1,2-a]quinoline derivatives. AB - With the cooperation of Cram's phenonium ion, a novel cascade reaction was illustrated to construct pyrrolo[1,2-a]quinolines as a sole diastereoisomer in good to excellent yields. Preliminary mechanistic studies revealed that the gamma lactam ring and electron-rich arene are important driving forces for ring contraction. PMID- 20302283 TI - Longitudinal surface plasmon resonance based gold nanorod biosensors for mass spectrometry. AB - A "strategy" for analyte capture/ionization based on chemical derivatization of gold nanorods and infrared laser desorption ionization (IR-LDI) is described. This is the first example of laser desorption/ionization of biomolecules using gold nanorods irradiated with an IR laser. LDI is performed at wavelengths (1064 nm) that overlap with the longitudinal surface plasmon resonance (LSPR) mode of gold nanorods. The absorbed energy from the laser facilitates desorption and ionization of the analyte. The wavelength of the LSPR band can be tuned by controlling the aspect ratio (length-to-diameter) of the nanorod. For example, the SPR band for Au nanorods having an aspect ratio of 5:1 is centered at approximately 840 nm, and this band overlaps with the 1064 nm output of a Nd:YAG laser. We show that a variety of biomolecules can be efficiently desorbed and ionized by 1064 nm irradiation of nanorods. We also show that analyte capture can be controlled by surface chemistry of the nanorods. The results of these studies are important for designing nanomaterial-based capture assays for mass spectrometry and interfacing nanomaterials with imaging/spatial profiling mass spectrometry experiments. PMID- 20302284 TI - Synthesis of necklace-like magnetic nanorings. AB - Necklace-like magnetite and maghemite nanorings, composed of magnetic nanoparticles (NPs) with average size about 40 nm, have been prepared via a solvothermal process in a colloidal solution by a self-assembly process. The composition, phase, and morphology of these nanorings have been characterized by X-ray diffraction, X-ray absorption, and transmission electron microscopy. In this paper, we discuss the influence of reaction conditions on the formation of nanorings structure including the amount of PVP in starting materials, reaction time, and temperature. On the basis of experimental observation, we supposed that magnetite NPs may first assemble into chains by magnetic dipole-dipole interactions. These dipolar chains, which are metastable structures relative to necklace-like nanorings, then produced the rings. So, the stability of chains may determine the yield, size, and morphologies of necklace-like nanorings. PMID- 20302285 TI - Surface reaction of sulfur-containing amino acids on Cu(110). AB - Adsorption behaviors of sulfur-containing amino acids, cysteine, methionine, and cystine molecules on Cu(110) surface were studied by core level photoelectron spectroscopy using synchrotron radiation. We found the following through the systematic comparisons of core level peaks such as S 2p, N 1s, and O 1s from different amino acids. At low coverage regimes, all the molecules form two distinct thiolate species, and their S 2p binding energy difference was about 0.9 eV. The relative populations of the two thiolates were different for different molecules and their coverage, which is due to the different bond strength of the sulfur-containing functional groups. At high coverage regimes, only cysteine molecules form zwitterionic state, which is related to the molecular ordering on Cu(110) surface. PMID- 20302286 TI - CHF2OCHF2 (HFE-134): IR spectrum and kinetics and products of the chlorine-atom initiated oxidation. AB - Smog chamber/FTIR techniques were used to measure k(Cl + CHF(2)OCHF(2)) = (5.7 +/ 1.5) x 10(-16) cm(3) molecule(-1) s(-1) in 700 Torr of N(2)/O(2) diluent at 296 +/- 1 K. This result is 100 times lower than the previous literature value. The chlorine-atom-initiated atmospheric oxidation of CHF(2)OCHF(2) gives COF(2) in a molar yield of (185 +/- 22) %. The IR spectrum was recorded, and a radiative efficiency of 0.44 W m(-2) ppb(-1) was determined. The results are discussed with respect to the atmospheric chemistry and environmental impact of CHF(2)OCHF(2). PMID- 20302287 TI - Viscosity of polyelectrolytes solutions in nanofilms. AB - We use a thin film pressure balance to probe the rheological properties of thin liquid films. These films are made from mixed aqueous solutions of surfactants and polyelectrolytes. They drain under applied pressure in a noncontinuous way due to a stratification process of the polyelectrolytes network. The stratification kinetics was studied for films stabilized by different surfactants. Using a theoretical model, it is possible to examine the effect of both the surfactant and the film thickness on the local dissipation. On one hand, it was observed that dissipation depends on the polyelectrolyte concentration only, regardless whether the surfactant is neutral or bears electric charges opposite to those of the polyelectrolyte. On the other hand, it was found that dissipation is stronger in thinner films. PMID- 20302288 TI - Poly(N-isopropylacrylamide)-tethered silicate platelets for colloidal dispersion of conjugated polymers with thermoresponsive and photoluminescence properties. AB - Poly(N-isopropylacrylamide)-tethered nanosilicate platelets (NSP-PNiPAAm) have been synthesized by covalently bonding the polymer onto the surfaces of silicate platelets of nanometer dimension, and this class of nanohybrids has proved to be effective for dispersing water-insoluble conjugated polymers (CPs). Simple pulverization of poly[2-methoxy-5-(2'-ethylhexyloxy)-1,4-phenylenevinylene] (MEH PPV) with NSP-PNiPAAm rendered the powder material dispersible in water, whereupon it displayed thermoresponsive properties at 37.5 degrees C and CP particle size variation between ca. 50 and 100 nm by SEM observation. The same dispersion had a maximum UV-vis absorption at 524 nm and PL emission at 605 nm. The PL emission was significantly higher at 4 degrees C than at 45 degrees C. Being coated as a film, it showed an orange emission under an ultraviolet lamp, consistent with the PL measurement. The water-borne process of dispersing the CP in aqueous media by the presence of NSP-PNiPAAm and followed by film formation to demonstrate a unique method of manipulating hydrophobic conjugated polymers in a facile manner. PMID- 20302289 TI - Nanoscale free-carrier profiling of individual semiconductor nanowires by infrared near-field nanoscopy. AB - We report quantitative, noninvasive and nanoscale-resolved mapping of the free carrier distribution in InP nanowires with doping modulation along the axial and radial directions, by employing infrared near-field nanoscopy. Owing to the technique's capability of subsurface probing, we provide direct experimental evidence that dopants in interior nanowire shells effectively contribute to the local free-carrier concentration. The high sensitivity of s-SNOM also allows us to directly visualize nanoscale variations in the free-carrier concentration of wires as thin as 20 nm, which we attribute to local growth defects. Our results open interesting avenues for studying local conductivity in complex nanowire heterostructures, which could be further enhanced by near-field infrared nanotomography. PMID- 20302290 TI - Boron dipyrromethene (Bodipy) phosphorescence revealed in [Ir(ppy)(2)(bpy C[triple bond]C-bodipy)](+). AB - The synthesis, structural characterization, electrochemistry, and molecular photophysics of [Ir(ppy)(2)(bpy-C[triple bond]C-Bodipy)](PF(6)), where ppy is 2 phenylpyridine and bpy-C[triple bond]C-Bodipy is 5-ethynyl-2,2'-bipyridine-8 phenyl-1,3,5,7-tetramethyl-4,4-bis(2,5-dioxaoct-7-ynyl)-4-bora-3a,4a-diaza-s indacene (4), is presented. Static and dynamic photoluminescence and absorption measurements in conjunction with cyclic voltammetry were employed to elucidate the nature of the intramolecular energy transfer processes occurring in the excited state of the title chromophore. Parallel studies were performed on appropriate model chromophores (2 and 3) intended to represent the photophysics of the isolated molecular subunits, that is, triplet metal-to-ligand-charge transfer ((3)MLCT) and triplet Bodipy intraligand ((3)IL) excited states, respectively. Upon charge transfer excitation of the title chromophore, the (3)MLCT based phosphorescence readily observed in 2 (Phi(em) = 0.027, tau = 243 ns) is quantitatively quenched resulting from production of the (3)Bodipy excited state through intramolecular triplet-triplet energy transfer. The formation of the (3)Bodipy-localized excited state is confirmed by features in the transient absorption difference spectrum, extended excited-state lifetime (tau = 25 micros), as well the observation of (3)IL Bodipy-based phosphorescence detected at 730 nm at 77 K. The low temperature Bodipy phosphorescence is readily produced in 4 as a result of the internal Ir(III) heavy atom. PMID- 20302291 TI - Stabilized (111)in-labeled sCCK8 analogues for targeting CCK2-receptor positive tumors: synthesis and evaluation. AB - Radiolabeled cholecystokinin-8 (CCK8) peptide analogues can be used for peptide receptor radionuclide imaging and therapy for tumors expressing CCK2/gastrin receptors. Earlier findings indicated that sulfated CCK8 (sCCK8, Asp-Tyr(OSO(3)H) Met-Gly-Trp-Met-Asp-Phe-NH(2)) may have better characteristics for peptide receptor radionuclide therapy (PRRT) than gastrin analogues. However, sCCK8 contains an easily hydrolyzable sulfated tyrosine residue and two methionine residues which are prone to oxidation. Here, we describe the synthesis of stabilized sCCK8 analogues, resistant to hydrolysis and oxidation. Hydrolytic stability was achieved by replacement of the Tyr(OSO(3)H) moiety by a robust isosteric sulfonate, Phe(p-CH(2)SO(3)H). Replacement of methionine by norleucine (Nle) or homopropargylglycine (HPG) avoided undesired oxidation side-reactions. The phenylalanine analogue Phe(p-CH(2)SO(3)H) of l-tyrosine, synthesized by a modification of known synthetic routes, was incorporated in three peptides: sCCK8[Phe(2)(p-CH(2)SO(3)H),Met(3,6)], sCCK8[Phe(2)(p-CH(2)SO(3)H),Nle(3,6)], and sCCK8[Phe(2)(p-CH(2)SO(3)H),HPG(3,6)]. All peptides were N-terminally conjugated with the macrocyclic chelator DOTA (1,4,7,10-tetraazacyclododecane-N,N',N'',N''' tetraacetic acid) and radiolabeled with In-111. In vitro binding assays on CCK2R expressing HEK293 cells revealed that all three peptides showed specific binding and receptor-mediated internalization, with binding affinity values (IC(50)) in the nanomolar range. In vitro oxidation studies demonstrated that peptides with Nle or HPG indeed were resistant to oxidation. In vivo targeting studies in mice with AR42J tumors showed that tumor uptake was highest for (111)In-DOTA-sCCK8 and (111)In-DOTA-sCCK8[Phe(2)(p-CH(2)SO(3)H),Nle(3,6)] (4.78 +/- 0.64 and 4.54 +/- 1.15%ID/g, respectively, 2 h p.i.). The peptide with the methionine residues replaced by norleucine ((111)In-DOTA-sCCK8[Phe(2)(p-CH(2)SO(3)H), Nle(3,6)]) showed promising in vivo characteristics and will be further investigated for radionuclide imaging and therapy of CCK2R-expressing tumors. PMID- 20302292 TI - Phosphinite thioethers derived from chiral epoxides. Modular P,S-ligands for Pd catalyzed asymmetric allylic substitutions. AB - A new family of modular P,S-ligands has been prepared from enantiopure arylglycidols. These ligands have been iteratively optimized with respect to four different structural parameters for use in Pd-catalyzed allylic substitutions. As a final output, highly active and enantioselective ligands for these synthetically important transformations have been developed, and the factors controlling their catalytic behavior have been rationalized. From a methodological point of view, a convenient procedure for the regioselective ring opening of cis-glycidic esters with bulky thiols to yield the corresponding beta alkylthio-alpha-hydroxy carboxylic acids has been developed. PMID- 20302293 TI - Vertical distributions of plutonium and 137Cs in lacustrine sediments in northwestern china: quantifying sediment accumulation rates and source identifications. AB - We investigated the vertical distributions of 239+240Pu and 137Cs activities and 240Pu/239Pu atom ratios in two lakes in northwestern China. The 240Pu/239Pu atom ratio from the Chinese nuclear test (CNT) site at Lop Nor is too complicated to identify the regional fallout source. However, radionuclides from the test site may be resolved mainly by the vertical distribution of radionuclides because there is no overlap between the global fallout peak and the local fallout peak. We analyzed Pu isotopes and 137Cs in sediments from two lakes (Sugan and Shuangta) located in northwestern China, near the CNT, and Lake Sihailongwan located in northeastern China to date recent lacustrine sediments and resolve global/local fallout sources. The apparently low 240Pu/239Pu atom ratio of 0.103 +/- 0.010 at Lake Sugan was likely representative of the fallout from the Lop Nor site. Our results also demonstrated that the 239+240Pu activity was more useful for recent chronology of lacustrine sediments, compared to 137Cs. Sediment accumulation rates of 0.651, 0.058-0.061, and 0.015 g x cm(-2) x a(-1) for sediment cores of Lake Shuangta, Lake Sugan and Lake Sihailongwan, respectively, were obtained by using the 239+240Pu fallout peak as a discrete time marker for 1964. The respective contributions of 137Cs and 239+240Pu from the CNT were estimated to be about 40 and 27% for Lake Sugan and 36 and 20% for Lake Shuangta. Plutonium isotopes in lacustrine sediments were proven to be useful for quantifying sediment accumulation rates and for source identification of the radioactive contamination. PMID- 20302294 TI - Palladium-catalyzed reductive homocoupling of aromatic halides and oxidation of alcohols. AB - Palladium-catalyzed reductive homocoupling of aromatic halides can be performed in alcohol solutions without any auxiliary reducing reagents. Pd(dppf)Cl(2) [dppf = 1,1'-bis(diphenylphosphino)ferrocene] has been shown as the most effective catalyst among the palladium catalysts screened for the model reductive homocoupling of iodobenzene in alcoholic solutions. The reduction of iodobenzene is stoichiometrically coupled with the oxidation of solvent alcohol (3-pentanol). The X-ray photoelectron spectroscopic (XPS) studies clearly indicate that the oxidation of solvent alcohol molecules is involved with the in situ regeneration of the reductive Pd(0)(dppf) active species, indicating that the solvent alcohol also reacts as a reducing reagent for the reductive homocoupling of aromatic halides. Elimination of the external reducing reagents will simplify the product separation and purification. Base is essential for the success of the Pd(dppf)Cl(2)-catalyzed redox reaction as 2 molar equiv of base is needed to neutralize the acid byproduct formed. Biaryls are the predominant products for the Pd(dppf)Cl(2)-catalyzed reductions of the unsubstituted aromatic halides in 3 pentanol solution, whereas the dehalogenation products are predominant for the Pd(dppf)Cl(2)-catalyzed reductions of the substituted aromatic halides. The reaction mechanisms have been discussed for the palladium-mediated concomitant reduction of aromatic halides and oxidation of alcohols without any auxiliary reductants and oxidants. PMID- 20302295 TI - The low-temperature inflection observed in neutron scattering measurements of proteins is due to methyl rotation: direct evidence using isotope labeling and molecular dynamics simulations. AB - There is increasing interest in the contribution of methyl groups to the overall dynamics measured by neutron scattering experiments of proteins. In particular an inflection observed in atomic mean square displacements measured as a function of temperature on high resolution spectrometers (approximately 1 microeV) was explained by the onset of methyl group rotations. By specifically labeling a non methyl-containing side-chain in a native protein system, the purple membrane, and performing neutron scattering measurements, we here provide direct experimental evidence that the observed inflection is indeed due to methyl group rotations. Molecular dynamics simulations reproduce the experimental data, and their analysis suggests that the apparent transition is due to methyl group rotation entering the finite instrumental resolution of the spectrometer. Methyl group correlation times measured by solid state NMR in the purple membrane, taken from previous work, support the interpretation. PMID- 20302296 TI - A stable 1,2-disilacyclohexene and its 14-electron palladium(0) complex. AB - A novel stable cyclic disilene, 1,2-diphenyl-3,3,6,6-tetrakis(trimethylsilyl)-1,2 disilacyclohexene (1), was synthesized via the reaction of the corresponding 1,4 dilithiobutane with phenylchlorosilane. This new strategy would be applicable to the synthesis of stable cyclic disilenes having rather small residual substituents on unsaturated silicon atoms. A stable tricoordinate Y-shaped disilene palladium complex, 2, that was synthesized by the reaction of 1 with bis(tricyclohexylphosphine)palladium was found to have the strongest pi-complex character among known disilene palladium complexes. PMID- 20302297 TI - A highly tunable stereoselective olefination of semistabilized triphenylphosphonium ylides with N-sulfonyl imines. AB - The Wittig reaction involving direct olefination of triphenylphosphonium ylides (Ph(3)P horizontal lineCHR) with aldehydes is arguably the most often used method for alkene synthesis, but in general it yields mixtures of Z- and E-alkenes for semistabilized triphenylphosphonium ylides (R = aryl or vinyl). We have developed a simple and efficient protocol to improve the stereoselectivity significantly by replacing the aldehydes used in the Wittig reaction with N-sulfonyl imines, which possess distinct electronic and steric properties relative to aldehydes. A broad range of aromatic, alpha,beta-unsaturated, and aliphatic imines bearing appropriate N-sulfonyl groups smoothly undergo olefination reaction with various benzylidenetriphenylphosphoranes or allylidenetriphenylphosphoranes under mild reaction conditions to afford an array of both Z- and E-isomers of conjugated alkenes in good to excellent yields and with greater than 99:1 stereoselectivity. Moreover, this tunable protocol has been successfully applied to the highly stereoselective synthesis of two anticancer agents, DMU-212 and its Z-isomer. PMID- 20302298 TI - pH-Responsive quantum dots via an albumin polymer surface coating. AB - Multifunctional peptide-polymer hybrid materials have been applied as efficient and biocompatible quantum-dot coating materials. Significant pH responsiveness (e.g., an influence of the pH on the quantum yields of the peptide-polymer/QDs) was found and is attributed to conformational rearrangements of the peptide backbone. PMID- 20302299 TI - An active-site phenylalanine directs substrate binding and C-H cleavage in the alpha-ketoglutarate-dependent dioxygenase TauD. AB - Enzymes that cleave C-H bonds are often found to depend on well-packed hydrophobic cores that influence the distance between the hydrogen donor and acceptor. Residue F159 in taurine alpha-ketoglutarate dioxygenase (TauD) is demonstrated to play an important role in the binding and orientation of its substrate, which undergoes a hydrogen atom transfer to the active site Fe(IV)=O. Mutation of F159 to smaller hydrophobic side chains (L, V, A) leads to substantially reduced rates for substrate binding and for C-H bond cleavage, as well as increased contribution of the chemical step to k(cat) under steady-state turnover conditions. The greater sensitivity of these substrate-dependent processes to mutation at position 159 than observed for the oxygen activation process supports a previous conclusion of modularity of function within the active site of TauD (McCusker, K. P.; Klinman, J. P. Proc. Natl. Acad. Sci. U.S.A. 2009, 106, 19791-19795). Extraction of intrinsic deuterium kinetic isotope effects (KIEs) using single turnover transients shows 2- to 4-fold increase in the size of the KIE for F159V in relation to wild-type and F159L. It appears that there is a break in behavior following removal of a single methylene from the side chain of F159L to generate F159V, whereby the protein active site loses its ability to restore the internuclear distance between substrate and Fe(IV)=O that supports optimal hydrogenic wave function overlap. PMID- 20302300 TI - Cyclic sulfones as novel P3-caps for hepatitis C virus NS3/4A (HCV NS3/4A) protease inhibitors: synthesis and evaluation of inhibitors with improved potency and pharmacokinetic profiles. AB - HCV infection affects more than 170 million people worldwide and many of those patients will reach the end stage complications of the disease which include hepatocarcinoma and liver failure. The success rate for treatment of patients infected with genotype-1 is about 40%. Therefore, novel treatments are needed to combat the infection. The HCV NS3 protease inhibitor Boceprevir (1) was reported by our research group and efforts continue for the discovery of more potent compounds with improved pharmacokinetic profiles. A new series of HCV NS3 protease inhibitors having a cyclic sulfone P3-cap have been discovered. Compounds 43 and 44 showed K(i)* values in the single-digit nM range and their cellular potency was improved by 10-fold compared to 1. The pharmacokinetic profiles of 43 and 44 in rats and monkeys were also improved to achieve higher plasma levels after oral administration. PMID- 20302302 TI - (1S)-1,5-anhydro-1-[5-(4-ethoxybenzyl)-2-methoxy-4-methylphenyl]-1-thio-D glucitol (TS-071) is a potent, selective sodium-dependent glucose cotransporter 2 (SGLT2) inhibitor for type 2 diabetes treatment. AB - Derivatives of a novel scaffold, C-phenyl 1-thio-D-glucitol, were prepared and evaluated for sodium-dependent glucose cotransporter (SGLT) 2 and SGLT1 inhibition activities. Optimization of substituents on the aromatic rings afforded five compounds with potent and selective SGLT2 inhibition activities. The compounds were evaluated for in vitro human metabolic stability, human serum protein binding (SPB), and Caco-2 permeability. Of them, (1S)-1,5-anhydro-1-[5-(4 ethoxybenzyl)-2-methoxy-4-methylphenyl]-1-thio-D-glucitol (3p) exhibited potent SGLT2 inhibition activity (IC(50) = 2.26 nM), with 1650-fold selectivity over SGLT1. Compound 3p showed good metabolic stability toward cryo-preserved human hepatic clearance, lower SPB, and moderate Caco-2 permeability. Since 3p should have acceptable human pharmacokinetics (PK) properties, it could be a clinical candidate for treating type 2 diabetes. We observed that compound 3p exhibits a blood glucose lowering effect, excellent urinary glucose excretion properties, and promising PK profiles in animals. Phase II clinical trials of 3p (TS-071) are currently ongoing. PMID- 20302301 TI - Structure-activity relationships in toll-like receptor-2 agonistic diacylthioglycerol lipopeptides. AB - The N-termini of bacterial lipoproteins are acylated with a (S)-(2,3 bisacyloxypropyl)cysteinyl residue. Lipopeptides derived from lipoproteins activate innate immune responses by engaging Toll-like receptor 2 (TLR2) and are highly immunostimulatory and yet without apparent toxicity in animal models. The lipopeptides may therefore be useful as potential immunotherapeutic agents. Previous structure-activity relationships in such lipopeptides have largely been obtained using murine cells, and it is now clear that significant species specific differences exist between human and murine TLR responses. We have examined in detail the role of the highly conserved Cys residue as well as the geometry and stereochemistry of the Cys-Ser dipeptide unit. (R) Diacylthioglycerol analogues are maximally active in reporter gene assays using human TLR2. The Cys-Ser dipeptide unit represents the minimal part-structure, but its stereochemistry was found not to be a critical determinant of activity. The thioether bridge between the diacyl and dipeptide units is crucial, and replacement by an oxoether bridge results in a dramatic decrease in activity. PMID- 20302304 TI - Oxygen-isotope exchange rates for three isostructural polyoxometalate ions. AB - We compare oxygen-isotope exchange rates for all structural oxygens in three polyoxoniobate ions that differ by systematic metal substitutions of Ti(IV) --> Nb(V). The [H(x)Nb(10)O(28)]((6-x)-), [H(x)TiNb(9)O(28)]((7-x)-), and [H(x)Ti(2)Nb(8)O(28)]((8-x)-) ions are all isostructural yet have different Bronsted properties. Rates for sites within a particular molecule in the series differ by at least approximately 10(4), but the relative reactivities of the oxygen sites rank in nearly the same relative order for all ions in the series. Within a single ion, most structural oxygens exhibit rates of isotopic exchange that vary similarly with pH, indicating that each structure responds as a whole to changes in pH. Across the series of molecules, however, the pH dependencies for isotope exchanges and dissociation are distinctly different, reflecting different contributions from proton- or base-enhanced pathways. The proton enhanced pathway for isotope exchange dominates at most pH conditions for the [H(x)Ti(2)Nb(8)O(28)]((8-x)-) ion, but the base-enhanced pathways are increasingly important for the [H(x)TiNb(9)O(28)]((7-x)-) and [H(x)Nb(10)O(28)]((6-x)-) structures at higher pH. The local effect of Ti(IV) substitution could be assessed by comparing rates for structurally similar oxygens on each side of the [H(x)TiNb(9)O(28)]((7-x)-) ion and is surprisingly small. Interestingly, these nanometer-size structures seem to manifest the same general averaged amphoteric chemistry that is familiar for other reactions affecting oxides in water, including interface dissolution by proton- and hydroxyl-enhanced pathways. PMID- 20302305 TI - A new class of surfactants with multinuclear, inorganic head groups. AB - The main ability of amphiphilic molecules is to alter the energy of interfaces. They aid in the formation of various materials characterized by a high surface to volume ratio. Furthermore, amphiphiles tend to self-organize into structures of higher complexity. In the current study anionic surfactants containing a purely inorganic multinuclear head group of the polytungstate type R-[PW(11)O(39)](3-) were synthesized. Alkyl chains of different length were attached to the head group via siloxy bridges. Furthermore, the counterions could be varied. Ultimately, a heteropolyacid surfactant (H(+) as the counterion) could be prepared. The self-assembly behavior of the polyoxometalate surfactants into micelles and even lyotropic phases was studied. For instance, the formation of a phase with P6/mm symmetry containing hexagonally packed cylinders has been observed. Finally, it was possible to extend the functionality of classical amphiphiles. The polyoxometalate amphiphiles have been used for the emulsification of and, at the same time, as the initiator for the cationic polymerization of styrene. As a result, interesting organic-inorganic hybrid polymer latexes with surfaces containing heteropolyacid entities were prepared. PMID- 20302303 TI - Targeted delivery of paclitaxel to tumor cells: synthesis and in vitro evaluation. AB - We previously reported a novel drug delivery system, drug-linker-Phe-Phe-Arg methylketone (FFR-mk)-factor VIIa (fVIIa). The method utilizes tissue factor (TF), which is aberrantly and abundantly expressed on many cancer cells. The advantage of this delivery system is its ability to furnish a potent anticancer drug specifically to the tumor vasculature and cancer cells. In this paper, we describe the synthesis of paclitaxel (PTX)-Phe-Phe-Arg-chloromethyl ketone (FFR ck), followed by coupling with fVIIa to form PTX-FFR-mk-fVIIa. FFRck was separately linked to the OH groups at the C2' or C7 positions of PTX (C2'- or C7 PTX-FFRck), the C2' analogue exhibiting better activity against human head and neck squamous KB 3-1 cells. The activity order against PTX-sensitive KB 3-1 cells is C2'-PTX-FFRmk-fVIIa > PTX > C2'-PTX-FFRck. The C2' complex shows an IC(50) of 12 nM against the PTX-sensitive cell line and 130 nM against PTX-resistant cells. PMID- 20302307 TI - Electrostatic polarization makes a substantial contribution to the free energy of avidin-biotin binding. AB - Avidin-biotin is one of the strongest protein-ligand binding systems, with broad applications in biomedical science. Here we report a quantum-based computational study to help elucidate the mechanism of binding avidin to biotin (BTN1) and its close analogue, 2'-iminobiotin (BTN2). Our study reveals that electronic polarization of protein plays a critical role in stabilizing the beta sheet (Thr113-Arg122) at the binding site and makes a substantial contribution to the free energy of avidin-biotin binding. The current finding is in contradiction to the previous notion that electrostatic interaction has no effect on or makes an unfavorable contribution to the free energy of avidin-biotin binding. Our calculations also show that the difference in binding free energy of avidin to BTN1 and BTN2 is almost entirely due to the contribution of electrostatic interaction resulting from polarization-induced stabilization of a hydrogen bond between avidin and BTN1. The current result provides strong evidence that protein polarization accounts for the electrostatic contribution to binding free energy that was missing in previous studies of avidin-biotin binding. PMID- 20302308 TI - Intercalation of ethylene glycol into yttrium hydroxide layered materials. AB - Intercalation of ethylene glycol into layered yttrium hydroxide containing nitrate counterions was accomplished by heating the reagents in a methanol solution of sodium methoxide under autogenous pressure at 413 K for 20 h. The resulting crystalline material had an expanded interlayer distance of 10.96 A, confirming the intercalation of an ethylene glycol derived species. Characterization of the material by FT-IR spectroscopy, thermogravimetric analysis, and the catalytic transesterification of tributyrin with methanol was consistent with direct bonding of ethylene glycolate anions (O(2)C(2)H(5)(-)) to the yttrium hydroxide layers, forming Y-O-C bonds. The layers of the material are proposed to be held together by H-bonding between the hydroxyls of grafted ethylene glycol molecules attached to adjacent layers. Glycerol can also be intercalated into yttrium hydroxide layered materials by a similar method. PMID- 20302306 TI - Molecular basis for enantioselectivity in the (R)- and (S) hydroxypropylthioethanesulfonate dehydrogenases, a unique pair of stereoselective short-chain dehydrogenases/reductases involved in aliphatic epoxide carboxylation. AB - (R)- and (S)-2-hydroxypropyl-CoM (R-HPC and S-HPC) are produced as intermediates in bacterial propylene metabolism from the nucleophilic addition of coenzyme M to (R)- and (S)-epoxypropane, respectively. Two highly enantioselective dehydrogenases (R-HPCDH and S-HPCDH) belonging to the short-chain dehydrogenase/reductase family catalyze the conversion of R-HPC and S-HPC to 2 ketopropyl-CoM (2-KPC), which undergoes reductive cleavage and carboxylation to produce acetoacetate. In the present study, one of three copies of S-HPCDH enzymes present on a linear megaplasmid in Xanthobacter autotrophicus strain Py2 has been cloned and overexpressed, allowing the first detailed side by side characterization of the R-HPCDH and S-HPCDH enzymes. The catalytic triad of S HPCDH was found to consist of Y156, K160, and S143. R211 and K214 were identified as the amino acid residues coordinating the sulfonate of CoM in S-HPC. R211A and K214A mutants were severely impaired in the oxidation of S-HPC or reduction of 2 KPC but were largely unaffected in the oxidation and reduction of aliphatic alcohols and ketones. Kinetic analyses using R- and S-HPC as substrates revealed that enantioselectivity in R-HPCDH (value, 944) was dictated largely by differences in k(cat) while enantioselectivity for S-HPCDH (value, 1315) was dictated largely by changes in K(m). S-HPCDH had an inherent high enantioselectivity for producing (S)-2-butanol from 2-butanone that was unaffected by modulators that interact with the sulfonate binding site. The tertiary alcohol 2-methyl-2-hydroxypropyl-CoM (M-HPC) was a competitive inhibitor of R-HPCDH-catalyzed R-HPC oxidation, with a K(is) similar to the K(m) for R-HPC, but was not an inhibitor of S-HPCDH. The primary alcohol 2-hydroxyethyl-CoM was a substrate for both R-HPCDH and S-HPCDH with identical K(m) values. The pH dependence of kinetic parameters suggests that the hydroxyl group is a larger contributor to S-HPC binding to S-HPCDH than for R-HPC binding to R-HPCDH. It is proposed that active site constraints within the S-HPCDH prevent proper binding of R-HPC and M-HPC due to steric clashes with the improperly aligned methyl group on the C2 carbon, resulting in a different mechanism for controlling substrate specificity and enantioselectivity than present in the R-HPCDH. PMID- 20302309 TI - Stepwise and selective carborane substitution in the B(3,6) positions of a 16e CpCo half-sandwich complex containing a chelating ortho-carborane-1,2-dithiolate ligand. AB - The reactions of the 16e half-sandwich complex, CpCo(S(2)C(2)B(10)H(10)) (1), with alkynones at ambient temperature lead to complexes CpCo(S(2)C(2)B(10)H(9))(CH=CH-C(O)R) (R = Ph (2), 2-naphthyl (3)). Both 2 and 3 are still 16e half-sandwich complexes containing a B(3)-substituted ortho carborane-1,2-dithiolate ligand. Treatment of 2 with excess alkynes R(1)C[triple bond]CR(2) (R(1) = H, R(2) = Ph, C(O)Ph, CO(2)Me; R(1) = R(2) = CO(2)Me) affords five complexes, CpCo(S(2)C(2)B(10)H(8))(CH(2)CPh)(CH=CH-C(O)Ph) (4), CpCo(S(2)C(2)B(10)H(8))(CH=CH-C(O)Ph)(2) (5), CpCo(S(2)C(2)B(10)H(8))(CH=CH CO(2)Me)(CH=CH-C(O)Ph) (6), CpCo(S(2)C(2)B(10)H(9))(MeO(2)C-C=C-CO(2)Me)(CH=CH C(O)Ph) (7), and CpCo(S(2)C(2)B(10)H(9))(MeO(2)C-C=C-CO(2)Me)(2)(CH=CH-C(O)Ph) (8). Complex 4 is an 18e complex bearing a B-CH(2) unit. Both 5 and 6 retain a 16e half-sandwich structure but contain a B(3,6)-disubstituted ortho-carborane 1,2-dithiolate ligand. However, in 7 and 8 one or two alkynes are inserted into one of the Co-S bonds to generate 18e species, respectively. Heating 7 leads to the 16e complex, CpCo(S(2)C(2)B(10)H(8))(MeO(2)C-C=CH-CO(2)Me)(CH=CH-C(O)Ph) (9), having a B(3,6)-disubstituted ortho-carborane-1,2-dithiolate ligand as in 5 and 6. All complexes were fully characterized by spectroscopic techniques and elemental analysis. The solid-state structures of 2 and 3 and 5-9 were further characterized by X-ray structural analysis. PMID- 20302310 TI - Synthesis, structure, and electrochemistry of the dicluster molecular pincer [Pt(3)(mu-PBu(t)(2))(3)(CO)(2)](2)(mu-1',1'''-diethynylbiferrocene). AB - The CuI catalyzed dehydro-halogenation of 1',1'''-diethynylbiferrocene and {Pt(3)}Cl [{Pt(3)} = Pt(3)(mu-PBu(t)(2))(3)(CO)(2)] (1:2 molar ratio) in diethylamine gives in high yields the bicluster derivative [{Pt(3)}CC-(eta(5) C(5)H(4))Fe(eta(5)-C(5)H(4))](2), 3, in which two platinum triangles are connected by a diethynylbiferrocene spacer. In the structure of 3, confirmed by a diffractometric study, the two {Pt(3)} fragments lie, perfectly eclipsed, on the same side of the biferrocenyl moiety; this folded structure is also preferred in solution, as suggested by NMR Diffusion Ordered Spectroscopy (DOSY) and 1D Rotating-frame Overhauser Enhancement (ROE) measurements. Compound 3 exhibits a rich redox behavior, with a crowded sequence of six one-electron oxidation processes, the electrode potentials of which have been evaluated by digital simulations. On the basis of a spectroelectrochemical study, the first two oxidations are assigned to the iron centers of the diferrocenyl unit and the subsequent four electrons are removed from the {Pt(3)} units. PMID- 20302311 TI - Direct ab initio MD study on the electron capture dynamics of hydroperoxy radical (HOO)-water complexes. AB - The electron capture dynamics of hydroperoxy radical-water complexes have been investigated by means of direct density functional theory (DFT) molecular dynamics (MD) method to elucidate the solvation (hydration) effect on the reaction mechanism. The complexes composed of HOO and one to four water molecules, HOO(H(2)O)(n) (n = 1-4), were considered to be the hydrated HOO system. After the electron capture of n = 1, only solvent reorientation of H(2)O around HOO(-) occurred, and a stable complex (HOO(-)-H(2)O) was formed within 100 300 fs. In the case of n = 2-4, a proton of H(2)O was transferred from H(2)O to OOH(-), whereas H(2)O(2) and OH(-)(H(2)O)(n-1) were found as products. It was suggested that the HOO radical adsorbed on water cluster is efficiently converted in the H(2)O(2) without activation barrier after the electron capture of HOO. Time scales of proton transfer were calculated to be 200-300 fs. The mechanism of electron capture of HOO in polar stratospheric cloud was discussed on the basis of theoretical results. PMID- 20302312 TI - Computational study on nitronium and nitrosonium oxalate: potential oxidizers for solid rocket propulsion? AB - The enthalpies of formation for solid ionic nitrosonium oxalate, [NO](2)[O(2)C CO(2)], nitronium oxalate, [NO(2)](2)[O(2)C-CO(2)], as well as covalent bis(nitroso)oxalic acid, ON-O(2)C-CO(2)-NO, and oxalic acid dinitrate ester, O(2)N-O(2)C-CO(2)-NO(2), were calculated using the complete basis set (CBS-4M) method of Petersson and coworkers to obtain very accurate energies. For the nitrosonium species, the ionic form ([NO](2)[O(2)C-CO(2)]) was identified as the more stable isomer, whereas for the nitrosonium compound, the covalently bound dinitrate ester (O(2)N-O(2)C-CO(2)-NO(2)) was found to be more stable. The combustion parameters with respect to possible use as ingredients in solid rocket motors for both stable species were calculated using the EXPLO5 and the ICT code. The performance of an aluminized formulation with covalently bound dinitrate ester (O(2)N-O(2)C-CO(2)-NO(2)) was shown to be comparable to that of ammonium perchlorate/aluminum. This makes oxalic acid dinitrate ester a potentially interesting perchlorate-free and environmentally benign oxidizer for solid rocket propulsion. PMID- 20302313 TI - Platinum(II) and phosphorus MM3 force field parametrization for chromophore absorption spectra at room temperature. AB - Platinum(II) and phosphine MM3 force field parameters are derived from fits to the ground state potential energy surface at the level of Kohn-Sham density functional theory with employment of the B3LYP exchange-correlation functional. The parametrization includes bond stretch, angle bend, and torsional parameters for a planar platinum(II) center with phosphine and ethynyl ligands. The force field is used to study the dynamics of a fifth-generation dendrimer-coated platinum(II)organic compound in tetrahydrofurane solution at room temperature, and, based on a selection of conformations from the molecular dynamics simulation, the averaged linear absorption spectrum is determined with use of the CAM-B3LYP functional. The main absorption peak in the theoretical absorption spectrum is found at a transition wavelength of 325 nm with a full-width at half maximum of 26 nm due to conformational broadening. PMID- 20302315 TI - Electronic delocalization, energetics, and optical properties of tripalladium ditropylium halides, [Pd(3)(C(7)H(7))(2)X(3)](1-) (X = Cl(-), Br(-), and I(-)). AB - Here we report relativistic electronic structure calculations employing all electron density functional theory (DFT) including scalar and spin-orbit interaction, on the multimetallic sandwich compound [Pd(3)(C(7)H(7))(2)X(3)](1-) (X = Cl(-) (1), Br(-) (2), and I(-) (3)), which can be considered as a [Pd(3)X(3)](3-) fragment flanked by two ring-ligands [(C(7)H(7))(2)](2+). The calculations suggest that the [Pd(3)X(3)](3-)-ligand interaction is mainly arising from electrostatic contributions, where the formally zerovalent Pd atoms allows backdonation of charge from the halide X(1-) atoms to the [(C(7)H(7))(2)](2+) ligands, resulting in a net charge of about +0.4 for each Pd atoms that decreases from 1 to 3. The electronic delocalization estimated via the NICS indexes and the ELF function allows us to describe a significant stabilizing sigma-aromaticity at the center of the Pd(3) triangle, which decreases from [Pd(3)Cl(3)](3-) to [Pd(3)I(3)](3-) (1 to 3) due to the softer character of the iodine counterpart, that donates extra charge to the ligands. The calculated electronic transitions via TD-DFT are in reasonable agreement with the experimental data obtained in CH(2)Cl(2) solution, indicating that the most intense transition involves a core-centered [Pd(3)X(3)](3) transition toward the [(C(7)H(7))(2)](2+) ligands, with mainly X(1-) character in the former molecular spinor that is responsible for the variation of the observed lambda(max) according to the variation of X(1-). PMID- 20302314 TI - Ladder polyether synthesis via epoxide-opening cascades directed by a disappearing trimethylsilyl group. AB - Epoxide-opening cascades offer the potential to construct complex polyether natural products expeditiously and in a manner that emulates the biogenesis proposed for these compounds. Herein we provide a full account of our development of a strategy that addresses several important challenges of such cascades. The centerpiece of the method is a trimethylsilyl (SiMe(3)) group that serves several purposes and leaves no trace of itself by the time the cascade has come to an end. The main function of the SiMe(3) group is to dictate the regioselectivity of epoxide opening. This strategy is the only general method of effecting endo selective cascades under basic conditions. PMID- 20302316 TI - Calorimetric and diffractometric evidence for the sequential crystallization of buffer components and the consequential pH swing in frozen solutions. AB - Sequential crystallization of succinate buffer components in the frozen solution has been studied by differential scanning calorimetry and X-ray diffractometry (both laboratory and synchrotron sources). The consequential pH shifts were monitored using a low-temperature electrode. When a solution buffered to pH < pK(a)(2) was cooled from room temperature (RT), the freeze-concentrate pH first increased and then decreased. This was attributed to the sequential crystallization of succinic acid, monosodium succinate, and finally disodium succinate. When buffered to pH > pK(a)(2), the freeze-concentrate pH first decreased and then increased due to the sequential crystallization of the basic (disodium succinate) followed by the acidic (monosodium succinate and succinic acid) buffer components. XRD provided direct evidence of the crystallization events in the frozen buffer solutions, including the formation of disodium succinate hexahydrate [Na(2)(CH(2)COO)(2).6H(2)O]. When the frozen solution was warmed in a differential scanning calorimeter, multiple endotherms attributable to the melting of buffer components and ice were observed. When the frozen solutions were dried under reduced pressure, ice sublimation was followed by dehydration of the crystalline hexahydrate to a poorly crystalline anhydrate. However, crystalline succinic acid and monosodium succinate were retained in the final lyophiles. The pH and the buffer salt concentration of the prelyo solution influenced the crystalline salt content in the final lyophile. The direction and magnitude of the pH shift in the frozen solution depended on both the initial pH and the buffer concentration. In light of the pH-sensitive nature of a significant fraction of pharmaceuticals (especially proteins), extreme care is needed in both the buffer selection and its concentration. PMID- 20302318 TI - Modeling the rovibrationally excited C2H4OH radicals from the photodissociation of 2-bromoethanol at 193 nm. AB - This study photolytically generates, from 2-bromoethanol photodissociation, the 2 hydroxyethyl radical intermediate of the OH + ethene reaction and measures the velocity distribution of the stable radicals. We introduce an impulsive model to characterize the partitioning of internal energy in the C(2)H(4)OH fragment. It accounts for zero-point and thermal vibrational motion to determine the vibrational energy distribution of the nascent C(2)H(4)OH radicals and the distribution of total angular momentum, J, as a function of the total recoil kinetic energy imparted in the photodissociation. We render this system useful for the study of the subsequent dissociation of the 2-hydroxyethyl radical to the possible asymptotic channels of the OH + ethene reaction. The competition between these channels depends on the internal energy and the J distribution of the radicals. First, we use velocity map imaging to separately resolve the C(2)H(4)OH + Br((2)P(3/2)) and C(2)H(4)OH + Br((2)P(1/2)) photodissociation channels, allowing us to account for the 10.54 kcal/mol partitioned to the Br((2)P(1/2)) cofragment. We determine an improved resonance enhanced multiphoton ionization (REMPI) line strength for the Br transitions at 233.681 nm (5p (4)P(1/2) <-- 4p (2)P(3/2)) and 234.021 nm (5p (2)S(1/2) <-- 4p (2)P(1/2)) and obtain a spin-orbit branching ratio for Br((2)P(1/2)):Br((2)P(3/2)) of 0.26 +/- 0.03:1. Energy and momentum conservation give the distribution of total internal energy, rotational and vibrational, in the C(2)H(4)OH radicals. Then, using 10.5 eV photoionization, we measure the velocity distribution of the radicals that are stable to subsequent dissociation. The onset of dissociation occurs at internal energies much higher than those predicted by theoretical methods and reflects the significant amount of rotational energy imparted to the C(2)H(4)OH photofragment. Instead of estimating the mean rotational energy with an impulsive model from the equilibrium geometry of 2-bromoethanol, our model explicitly includes weighting over geometries across the quantum wave function with zero, one, and two quanta in the harmonic mode that most strongly alters the exit impact parameter. The model gives a nearly perfect prediction of the measured velocity distribution of stable radicals near the dissociation onset using a G4 prediction of the C-Br bond energy and the dissociation barrier for the OH + ethene channel calculated by Senosiain et al. (J. Phys. Chem. A 2006, 110, 6960). The model also indicates that the excited state dissociation proceeds primarily from a conformer of 2 bromoethanol that is trans across the C-C bond. We discuss the possible extensions of our model and the effect of the radical intermediate's J distribution on the branching between the OH + ethene product channels. PMID- 20302319 TI - Electrophilic aromatic substitution: the role of electronically excited states. AB - Electrophilic aromatic substitutions (EAS), one of the most extensively studied organic reactions, can be considered under certain circumstances as a photochemical reaction without light. Thermochemical considerations show that in the gas phase, the reaction system (electrophile plus aromatic neutral) is often found initially in an electronically excited state, whereas the reaction products are formed on the ground state potential energy surface (PES). The crossing to the ground state is usually very rapid, so that the rate-determining steps take place on the ground state surface. It is shown that after the crossing (through a conical intersection (CI)), the system can be found on different parts of the ground state potential surface. In particular, the CI is connected without a barrier to all moieties assumed to be important in the reaction (pi complex, radical pair, and sigma complex). In some cases, due to a relatively low electron affinity of the electrophile and bond reorganization, the reaction starts on the ground state PES; a conical intersection exists in these cases, but is not accessed by the reactants. The topology of the reaction surface due to the avoided crossing is reminiscent of that in which an actual crossing takes place. The paper provides a comprehensive model for several EAS reactions. The CIs are located computationally, and an energy level diagram is proposed for some representative EAS reactions. PMID- 20302320 TI - Reaction rates and mechanism of the ascorbic acid oxidation by molecular oxygen facilitated by Cu(II)-containing amyloid-beta complexes and aggregates. AB - A forefront of the research on Alzheimer's disease (AD) is the interaction of amyloid beta (Abeta) peptides with redox metal ions (e.g., Cu(II), Fe(III), and Fe(II)) and the biological relevance of the Abeta-metal complexes to neuronal cell loss and homeostasis of essential metals and other cellular species. This work is concerned with the kinetic and mechanistic studies of the ascorbic acid oxidation reaction by molecular oxygen that is facilitated by Cu(II) complexes with Abeta(1-16), Abeta(1-42), and aggregates of Abeta(1-42). The reaction rate was found to linearly increase with the concentrations of Abeta-Cu(II) and dissolved oxygen and be invariant with high ascorbic acid concentrations. The rate constants were measured to be 117.2 +/- 15.4 and 15.8 +/- 2.8 M(-1) s(-1) at low (<100 muM) and high AA concentrations, respectively. Unlike free Cu(II), in the presence of AA, Abeta-Cu(II) complexes facilitate the reduction of oxygen by producing H(2)O(2) as a major product. Such a conclusion is drawn on the basis that the reaction stoichiometry between AA and O(2) is 1:1 when the Abeta concentration is kept at a much greater value than that of Cu(II). A mechanism is proposed for the AA oxidation in which the oxidation states of the copper center in the Abeta complex alternates between 2+ and 1+. The catalytic activity of Cu(II) toward O(2) reduction was found to decrease in the order of free Cu(II) > Abeta(1-16)-Cu(II) > Abeta(1-42)-Cu(II) > Cu(II) complexed by the Abeta oligomer/fibril mixture > Cu(II) in Abeta fibrils. The finding that Cu(II) in oligomeric and fibrous Abeta aggregates possesses considerable activity toward H(2)O(2) generation is particularly significant, since in senile plaques of AD patients the coexisting copper and Abeta aggregates have been suggested to inflict oxidative stress through the production of reactive oxygen species (ROS). Although Cu(II) bound to oligomeric and fibrous Abeta aggregates is less effective than free Cu(II) and the monomeric Abeta-Cu(II) complex in producing ROS, in vivo the Cu(II)-containing Abeta oligomers and fibrils might be more biologically relevant given their stronger association with cell membranes and the closer proximity of ROS to cell membranes. PMID- 20302321 TI - Computational backbone mutagenesis of Abeta peptides: probing the role of backbone hydrogen bonds in aggregation. AB - Using replica exchange molecular dynamics (REMD) and united atom implicit solvent model we examine the role of backbone hydrogen bonds (HBs) in Abeta aggregation. The importance of HBs appears to depend on the aggregation stage. The backbone HBs have little effect on the stability of Abeta dimers or on their aggregation interface. The HBs also do not play a critical role in initial binding of Abeta peptides to the amyloid fibril. Their elimination does not change the continuous character of Abeta binding nor its temperature. However, cancellation of HBs forming between incoming Abeta peptides and the fibril disrupts the locked fibril like states in the bound peptides. Without the support of HBs, bound Abeta peptides form few long beta-strands on the fibril edge. As a result, the deletion of peptide-fibril HBs is expected to impede fibril growth. As for the peptides bound to Abeta fibril the deletion of interpeptide HBs reduces the beta propensity in the dimers making them less competent for amyloid assembly. These simulation findings together with the backbone mutagenesis experiments suggest that a viable strategy for arresting fibril growth is the disruption of interpeptide HBs. PMID- 20302323 TI - Organic-inorganic composite nanocoatings with superhydrophobicity, good transparency, and thermal stability. AB - Superhydrophobic, highly transparent, and stable organic-inorganic composite nanocoating is successfully prepared by a simple sol-gel dip-coating method. This method involves control of the aggregation of inorganic colloid particles by polymerization and ultrasonic vibration to create the desired micro/nanostructure in the coating. Superhydrophobicity and transparency of the coating can be controlled by adjusting the initial concentration of monomer and the size of aggregates in the sol-gel. Thus, superhydrophobicity and high transparency can be concurrently achieved in a single coating. The prepared coating also possesses good thermal stability. Its superhydrophobicity can be maintained from 20 to 90 degrees C. PMID- 20302324 TI - Expeditious synthesis of benzopyrans via Lewis acid-catalyzed C-H functionalization: remarkable enhancement of reactivity by an ortho substituent. AB - An expeditious construction of a benzopyran skeleton via Lewis acid-catalyzed C-H functionalization was achieved. In this process, a [1,5] hydride shift and 6-endo cyclization successively occurred to give benzopyrans. The presence of substituents ortho to the alkoxy group significantly enhanced the reactivity, affording the desired compounds in excellent chemical yields with short reaction times. PMID- 20302325 TI - Selective synthesis of allenes and alkynes through ligand-controlled, palladium catalyzed decarboxylative hydrogenolysis of propargylic formates. AB - Ligand-controlled regioselective palladium-catalyzed decarboxylative hydrogenolysis of propargylic formates is described. A wide range of allenes and alkynes were obtained by using either 1,2-diphenylphosphinoethane (DPPE) or 1,6 bisdiphenylphosphinohexane (DPPH) as a catalyst ligand. PMID- 20302326 TI - Metabonomics in ulcerative colitis. AB - A recent publication in the Journal of Proteome Research applied metabolic profiling ("metabonomics") to ulcerative colitis; several different biosamples were investigated ( J. Proteome Res. 2010 , 9 , 954 - 962 ). Comparing urinary profiles, no differences were found between cases and controls; in a previously published study ( Am. J. Gastroenterol. 2009 , 104 , 1435 - 1444 ), we had found significant differences. In this correspondence, the reasons for our experimental and analytical approach are explained, and the negative results of the Journal of Proteome Research study are discussed. PMID- 20302328 TI - Proteomic analysis of plasma from patients undergoing coronary artery bypass grafting reveals a protease/antiprotease imbalance in favor of the serpin alpha1 antichymotrypsin. AB - We used proteomics to identify systematic changes in the plasma proteins of patients undergoing coronary artery bypass grafting (CABG) by means of cardiopulmonary bypass surgery. It is known that, after CABG, a complex systemic inflammatory responses ensues that favors the occurrence of adverse postoperative complications frequently recognizing inflammation itself and/or thrombosis as the underlying mechanism. We found a marked and persistent postoperative increase in the levels of the serpin-protease inhibitor alpha(1)-antichymotrypsin (alpha(1) ACT) that fully maintains the inhibitory activity blunting its protease substrate cathepsin G. An intraoperative increase followed by a rapid decline in proteases activation was documented, accompanied by a substantial induction of leucine-rich alpha-2-glycoprotein, a protein involved in neutrophilic granulocyte differentiation. Finally, a time-dependent alteration in the expression of haptoglobin, transthyretin, clusterin, and apoE was observed. In conclusion, we showed that after CABG, a protease/antiprotease imbalance occurs with early cathepsin G activation and a more delayed increase in alpha(1)-ACT. As cathepsin G is a serpin involved both in inflammation and coagulation activation, this confirms and expands the concept of a marked dysregulation of both inflammatory and hemostatic balances occurring after CABG. The pharmacologic modulation of this imbalance may be a new therapeutic target to reduce postoperative complications. PMID- 20302329 TI - Insight into the cellular uptake mechanism of a secondary amphipathic cell penetrating peptide for siRNA delivery. AB - Delivery of siRNA remains a major limitation to their clinical application, and several technologies have been proposed to improve their cellular uptake. We recently described a peptide-based nanoparticle system for efficient delivery of siRNA into primary cell lines: CADY. CADY is a secondary amphipathic peptide that forms stable complexes with siRNA and improves their cellular uptake independently of the endosomal pathway. In the present work, we have combined molecular modeling, spectroscopy, and membrane interaction approaches in order to gain further insight into CADY/siRNA particle mechanism of interaction with biological membrane. We demonstrate that CADY forms stable complexes with siRNA and binds phospholipids tightly, mainly through electrostatic interactions. Binding to siRNA or phospholipids triggers a conformational transition of CADY from an unfolded state to an alpha-helical structure, thereby stabilizing CADY/siRNA complexes and improving their interactions with cell membranes. Therefore, we propose that CADY cellular membrane interaction is driven by its structural polymorphism which enables stabilization of both electrostatic and hydrophobic contacts with surface membrane proteoglycan and phospholipids. PMID- 20302330 TI - Enantioselective synthesis of (+)-estrone exploiting a hydrogen bond-promoted Diels-Alder reaction. AB - Starting from Dane's diene and methylcyclopentenedione, (+)-estrone is synthesized along the Quinkert-Dane route in 24% total yield. The key step is an enantioselective Diels-Alder reaction promoted by an amidinium catalyst as efficiently as by a traditional Ti-TADDOLate Lewis acid. PMID- 20302333 TI - Temperature dependence of Henry's law constant for hydrogen cyanide. Generation of trace standard gaseous hydrogen cyanide. AB - Primary data for the temperature dependent solubility of HCN in water do not presently exist for low concentrations of HCN at environmentally or physiologically relevant temperatures. Henry's Law constant (K(H), M/atm) for the vapor-solution equilibrium of HCN was determined in 0.1 M sodium phosphate buffer (adjusted to pH 9.00 +/- 0.03 at 296.6 +/- 0.1 K) from 287-311 K. Stable gas phase concentrations of HCN are generated by established techniques, via air equilibration of aqueous cyanide partitioned by a microporous membrane. The effluent gaseous HCN, in equilibrium with the constant temperature aqueous cyanide, was collected in dilute NaOH and determined by a spectrophotometrically using cobinamide. The K(H) of HCN may be expressed as ln K(H) (M/atm) = (8205.7 +/- 341.9)/T - (25.323 +/- 1.144); r(2) = 0.9914) where T is the absolute temperature in K. This corresponds to 9.02 and 3.00 M/atm at 25 and 37.4 degrees C, respectively, compared to actual measurements of 9.86 and 3.22 at 25.0 and 37.8 degrees C, respectively. The technique also allows for convenient generation of trace levels of HCN at ppbv-ppmv levels that can be further diluted. PMID- 20302334 TI - Considering time in LCA: dynamic LCA and its application to global warming impact assessments. AB - The lack of temporal information is an important limitation of life cycle assessment (LCA). A dynamic LCA approach is proposed to improve the accuracy of LCA by addressing the inconsistency of temporal assessment. This approach consists of first computing a dynamic life cycle inventory (LCI), considering the temporal profile of emissions. Then, time-dependent characterization factors are calculated to assess the dynamic LCI in real-time impact scores for any given time horizon. Although generally applicable to any impact category, this approach is developed here for global warming, based on the radiative forcing concept. This case study demonstrates that the use of global warming potentials for a given time horizon to characterize greenhouse gas emissions leads to an inconsistency between the time frame chosen for the analysis and the time period covered by the LCA results. Dynamic LCA is applied to the US EPA LCA on renewable fuels, which compares the life cycle greenhouse gas emissions of different biofuels with fossil fuels including land-use change emissions. The comparison of the results obtained with both traditional and dynamic LCA approaches shows that the difference can be important enough to change the conclusions on whether or not a biofuel meets some given global warming reduction targets. PMID- 20302335 TI - Investigating lyophilization of lipid nanocapsules with fluorescence correlation spectroscopy. AB - This paper describes characterization of lyophilized lipid nanocapsules loaded with Alexa 488 by fluorescence correlation spectroscopy (FCS). Fluorimetry analysis of nanocapsules containing self-quenching concentrations of 5- and 6 carboxyfluorescein was performed to establish a point of reference for FCS. FCS results complemented the results obtained by fluorimetry for a bulk nanocapsule solution and provided additional information about the size and dye retention by individual nanocapsules. Using this method, we determined that nanocapsules composed of the thiol-functionalized lipids showed the best dye retention and the most consistent results. Dye retention, size, and photolysis efficiency of these thiol-functionalized nanocapsules doped with a far-red photosensitizer did not change substantially upon lyophilization and storage at -20 degrees C for up to 2 months, making lyophilization a suitable method for the long-term storage of nanocapsules with the appropriate lipid composition. PMID- 20302336 TI - SnO2-based dye-sensitized hybrid solar cells exhibiting near unity absorbed photon-to-electron conversion efficiency. AB - Improving the solar light harvesting and photon-to-electron conversion efficiency for hybrid, organic-inorganic photovoltaics are critical challenges. Titania based solid-state hybrid solar cells are moderately efficient at converting visible photons to electrons, but major electrical losses still remain. A material based paradigm shift is required to dramatically enhance the performance of these devices. Here, we present an investigation into solid-state dye sensitized solar cells (SDSCs) incorporating a molecular hole-transporter and mesoporous tin oxide electrodes, in place of titania usually employed. We investigate the influence of treating the surface of the SnO(2) with different oxides and find that MgO "passivated" SnO(2) electrodes demonstrate an unprecedented absorbed photon-to-electron conversion efficiency of near unity across a broad spectral range. A dual surface treatment of TiO(2) followed by MgO enables tuning of the solar cell photovoltage, fill factor, and efficiency with visible light absorbing cells delivering 3% solar-to-electrical full sun power conversion efficiency. PMID- 20302337 TI - Quantum confinement, surface roughness, and the conduction band structure of ultrathin silicon membranes. AB - We report direct measurements of changes in the conduction-band structure of ultrathin silicon nanomembranes with quantum confinement. Confinement lifts the 6 fold-degeneracy of the bulk-silicon conduction-band minimum (CBM), Delta, and two inequivalent sub-band ladders, Delta(2) and Delta(4), form. We show that even very small surface roughness smears the nominally steplike features in the density of states (DOS) due to these sub-bands. We obtain the energy splitting between Delta(2) and Delta(4) and their shift with respect to the bulk value directly from the 2p(3/2)-->Delta transition in X-ray absorption. The measured dependence of the sub-band splitting and the shift of their weighted average on degree of confinement is in excellent agreement with theory, for both Si(001) and Si(110). PMID- 20302338 TI - Enantioselective alkenylation via nickel-catalyzed cross-coupling with organozirconium reagents. AB - A new family of organometallic compounds, organozirconium reagents, are shown to serve as suitable partners in cross-coupling reactions of (activated) secondary alkyl electrophiles. Thus, the first catalytic method for coupling secondary alpha-bromoketones with alkenylmetal reagents has been developed, specifically, a mild, versatile, and stereoconvergent carbon-carbon bond-forming process that generates potentially labile beta,gamma-unsaturated ketones with good enantioselectivity. PMID- 20302339 TI - Kinetics of yttrium-ligand complexation monitored using hyperpolarized (89)Y as a model for gadolinium in contrast agents. AB - Hyperpolarization by dissolution dynamic nuclear polarization (DNP) enhances (89)Y spin magnetization by 3 to 4 orders of magnitude and provides a way to monitor yttrium-ligand complexation "on the fly" by means of (89)Y NMR. In this communication, we show an example of free yttrium Y(3+) being complexed with 1,4,7,10-tetrakis(acetamido)-1,4,7,10-tetraazacyclododecane (DOTAM) to form [Y(DOTAM)(H(2)O)](3+) as a model for gadolinium in contrast agents. PMID- 20302340 TI - Functionally relevant interplay between the Fe(4)S(4) cluster and CN(-) ligands in the active site of [FeFe]-hydrogenases. AB - [FeFe]-hydrogenases are highly efficient H(2)-evolving metalloenzymes that include cyanides and carbonyls in the active site. The latter is an Fe(6)S(6) cluster (the so-called H-cluster) that can be subdivided into a binuclear portion carrying the CO and CN(-) groups and a tetranuclear subcluster. The fundamental role of cyanide ligands in increasing the basicity of the H-cluster has been highlighted previously. Here a more subtle but crucial role played by the two CN( ) ligands in the active site of [FeFe]-hydrogenases is disclosed. In fact, QM/MM calculations on all-atom models of the enzyme from Desulfovibrio desulfuricans show that the cyanide groups fine-tune the electronic and redox properties of the active site, affecting both the protonation regiochemistry and electron transfer between the two subclusters of the H-cluster. Despite the crucial role of cyanides in the protein active site, the currently available bioinspired electrocatalysts generally lack CN(-) groups in order to avoid competition between the latter and the catalytic metal centers for proton binding. In this respect, we show that a targeted inclusion of phosphine ligands in hexanuclear biomimetic clusters may restore the electronic and redox features of the wild type H-cluster. PMID- 20302341 TI - A clomazone immunoassay to study the environmental fate of the herbicide in rice (Oryza sativa) agriculture. AB - The environmental impact of rice agriculture is poorly studied in developing countries, mainly due to limitations of the analytical capacity. Here, we report the development of a clomazone enzyme-linked immunosorbent assay as a fast and cost-effective tool to monitor the dissipation of this herbicide along the harvest. Antibodies were prepared using different strategies of hapten conjugation, and the best hapten/antibody pair was selected. It proved to be a reliable tool to measure the herbicide in the 2.0-20 ng/mL range in field samples, with excellent correlation with high-performance liquid chromatography results. The assay was used to study the dissipation of the herbicide in the floodwater of experimental rice paddies in Uruguay. Large differences in the residual amounts of herbicide were observed depending on the flooding practices. Because of its robustness and simplicity, the assay may be useful to delineate and monitor management practices that can contribute to minimizing the release of the herbicide in the environment. PMID- 20302342 TI - Systematic analysis of the content of 502 polyphenols in 452 foods and beverages: an application of the phenol-explorer database. AB - Considerable information on polyphenol content in foods is scattered in up to 1000 peer-reviewed publications and is therefore not easily exploited. Over 60000 food composition data have been collected from this literature and stored in the new Phenol-Explorer database ( www.phenol-explorer.eu ). Thirty-seven thousand data were selected after evaluation and aggregated separately according to 5 categories of analytical methods to generate mean content values for 502 compounds (glycosides, esters, or aglycones) in 452 foods. These data are exploited here in a first systematic analysis of the content in foods of these 502 polyphenols. These data will be useful for epidemiologists to determine polyphenol intake and associations with health and diseases in populations and for food scientitsts and food manufacturers to develop new products with optimized properties. PMID- 20302343 TI - Enrichment of armchair carbon nanotubes via density gradient ultracentrifugation: Raman spectroscopy evidence. AB - We have used resonant Raman scattering spectroscopy to fully analyze the relative abundances of different (n,m) species in single-walled carbon nanotube samples that are metallically enriched by density gradient ultracentrifugation. Strikingly, the data clearly show that our density gradient ultracentrifugation process enriches the metallic fractions in armchair and near-armchair species. We observe that armchair carbon nanotubes constitute more than 50% of each (2n + m) family. PMID- 20302344 TI - Structure of the ethylammonium nitrate surface: an X-ray reflectivity and vibrational sum frequency spectroscopy study. AB - X-ray reflectivity and vibrational sum frequency spectroscopy are used to probe the structure of the ethylammonium nitrate (EAN)-air interface. X-ray reflectivity reveals that the EAN-air interface is structured and consists of alternating nonpolar and charged layers that extend 31 A into the bulk. Vibrational sum frequency spectroscopy reveals interfacial cations have their ethyl moieties oriented toward air, with the CH(3) C(3) axis positioned approximately 36.5 degrees from interface normal. This structure is invariant between 15 and 51 degrees C. On account of its molecular symmetry, the orientation of the nitrate anion cannot be determined with certainty. PMID- 20302346 TI - Zinc chloride promoted formal oxidative coupling of aromatic aldehydes and isocyanides to alpha-ketoamides. AB - Reaction of aromatic aldehydes and isocyanides in the presence of N methylhydroxyamine, acetic acid, and zinc chloride affords the aryl alpha ketoamides in moderate to good yields. PMID- 20302345 TI - Porous polymer monolithic column with surface-bound gold nanoparticles for the capture and separation of cysteine-containing peptides. AB - A new porous polymer monolithic capillary column modified with gold nanoparticles that enables the selective capture of cysteine-containing peptides has been developed to reduce the complexity of peptide mixtures generated in bottom-up proteomic analysis. The column is prepared from a poly(glycidyl methacrylate-co ethylene dimethacrylate) monolith through reaction of some of its epoxide moieties with cysteamine to afford a monolith rich in surface thiol groups. In situ reduction of chloroauric acid within the column is then used to form gold nanoparticles attached to the surface of the pores of the monolith. This process preserves the excellent hydrodynamic properties of the monolithic column while providing a means to selectively retain cysteine-containing peptides from an analyte due to their high affinity for gold. Release of the retained peptides is subsequently achieved with an excess of 2-mercaptoethanol. The loading capacity determined for l-cysteine using frontal elution is 2.58 mumol/m. Since the gold thiol link is less stable at elevated temperatures, the adsorption capacity is recovered by washing the column at 80 degrees C for 2 h. While regeneration is easy, the multiplicity of bonds between the monolithic support and the gold nanoparticles prevents their elution even under harsh conditions such as treatment with pure 2-mercaptoethanol or treatment with boiling water for 5 h. Application of the gold modified monolith in tandem with a packed C18 capillary column is demonstrated with baseline separation of a peptide mixture achieved in a two step process. The first involves retention of cysteine-containing peptides in monolith with reversed phase separation of all other peptides, while the retained peptides are released from monolith and separated in the second step. PMID- 20302347 TI - Systematic electron crystallographic studies of self-assembled binary nanocrystal superlattices. AB - Multicomponent nanocrystal assemblies have received great attention due to their fundamental role in the study of self-assembly and novel physical properties arising from particle interactions. Here, we report the formation of the first binary nanocrystal superlattices (BNSLs) consisting of different-sized Fe3O4 nanocrystals. We establish a framework to systematically study the structure of BNSLs using a dual-axis tomography TEM holder. The tilt series obtained not only allows us to map the three-dimensional (3D) structure of icosahdedral AB(13) (ico AB(13)) and AlB(2)-type BNSLs but also uncovers the structural differences among the projections of ico-AB(13), cuboctahedral AB(13) (cub-AB(13)), and AlB(2). This structural characterization method is general and is important for further exploration of structural diversity in BNSLs and in the development of rigorous structure-property relationships in BNSLs. The formation of ico-AB(13) and AlB(2) BNSLs from electrostatically neutral Fe3O4 nanoparticles is consistent with the space-filling principles and further supports entropy as the dominant factor during the growth of these BNSLs. PMID- 20302348 TI - An unprecedented biogenetic-type chemical synthesis of 1(15-->11) abeotaxanes from normal taxanes. AB - A one-pot chemical process using BF(3).Et(2)O for the synthesis of a new class of 1(15-->11) abeotaxanes from normal taxanes has been developed. The chemical structures of rearranged 1(15-->11) abeotaxane were established by extensive 2D NMR spectroscopic data. PMID- 20302349 TI - Kinetics of chemical degradation in monoclonal antibodies: relationship between rates at the molecular and peptide levels. AB - This article describes a method to analyze the kinetics of monoclonal antibody degradation and to determine the quantitative relationship between the degradation rates observed at the molecular and peptide levels. The proposed model can be applied to any degradation pathway that can be well approximated by a first order reaction; if several pathways exist, the model assumes that they are independent. Three examples are presented to illustrate the benefits of this approach. For each case, the calculated fractions of species were compared to one or more data sets to demonstrate the good agreement between experimental results and model prediction. This method can serve as a valuable tool in interpreting chromatograms of degraded samples and predicting the population of species present at the molecular level when only data from degradation observed at the peptide level is available. This method further demonstrates how deviations from predictions of simple models can be used to unravel additional, unforeseen reactions. PMID- 20302350 TI - Controlled storage of ferrocene derivatives as redox-active molecules in dendrimers. AB - Dendritic polyphenylazomethines (DPA) could encapsulate ferroceniums by complexation of the electron-donating skeleton of the DPA imines. Upon addition of ferroceniums to a series of dendritic polyphenylazomethines (DPAGX, where X is the generation number, X = 1-4), the UV-vis spectra showed changes in a manner similar to that observed for the complexation of metal ions with DPAGX. Stepwise shifts in the isosbestic point were consistently observed with the number of imine groups in the first and second layers of the generation-4 dendrimer (DPAG4). DPAG2 and DPAG3 were also found to trap 6 equiv of ferroceniums. To investigate the complexation, UV-vis spectroscopy, (57)Fe Mossbauer spectroscopy, electrospray ionization-mass spectroscopy (ESI-MS), cyclic voltammetry (CV), and fluorescence spectroscopy were performed. We confirmed that neutral ferrocenes cannot complex with the imine group while ferroceniums can. Utilizing the redox property of ferrocenes, we were able to electrochemically control the encapsulation and release of ferrocenes into the DPA in a manner similar to redox responsive proteins such as ferritin. In addition to ferrocenes, oligoferrocenes could also be trapped in the DPA. The biferrocene cation(1+) was particularly suitable for electrochemical switching due to its stable mixed valence condition. The terferrocene dication(2+) encapsulated into DPAG4 could be fabricated into a thin film, which exhibited the near-infrared absorption of an intervalence charge transfer (IV-CT) band, pointing the way toward the use of such systems in material science. PMID- 20302351 TI - xComb: a cross-linked peptide database approach to protein-protein interaction analysis. AB - We developed an informatic method to identify tandem mass spectra composed of chemically cross-linked peptides from those of linear peptides and to assign sequence to each of the two unique peptide sequences. For a given set of proteins the key software tool, xComb, combs through all theoretically feasible cross linked peptides to create a database consisting of a subset of all combinations represented as peptide FASTA files. The xComb library of select theoretical cross linked peptides may then be used as a database that is examined by a standard proteomic search engine to match tandem mass spectral data sets to identify cross linked peptides. The database search may be conducted against as many as 50 proteins with a number of common proteomic search engines, e.g. Phenyx, Sequest, OMSSA, Mascot and X!Tandem. By searching against a peptide library of linearized, cross-linked peptides, rather than a linearized protein library, search times are decreased and the process is decoupled from any specific search engine. A further benefit of decoupling from the search engine is that protein cross-linking studies may be conducted with readily available informatics tools for which scoring routines already exist within the proteomic community. PMID- 20302353 TI - Metabolomic patterns in glioblastoma and changes during radiotherapy: a clinical microdialysis study. AB - We employed stereotactic microdialysis to sample extracellular fluid intracranially from glioblastoma patients, before and during the first five days of conventional radiotherapy treatment. Microdialysis catheters were implanted in the contrast enhancing tumor as well as in the brain adjacent to tumor (BAT). Reference samples were collected subcutaneously from the patients' abdomen. The samples were analyzed by gas chromatography-time-of-flight mass spectrometry (GC TOF MS), and the acquired data was processed by hierarchical multivariate curve resolution (H-MCR) and analyzed with orthogonal partial least-squares (OPLS). To enable detection of treatment-induced alterations, the data was processed by individual treatment over time (ITOT) normalization. One-hundred fifty-one metabolites were reliably detected, of which 67 were identified. We found distinct metabolic differences between the intracranially collected samples from tumor and the BAT region. There was also a marked difference between the intracranially and the subcutaneously collected samples. Furthermore, we observed systematic metabolic changes induced by radiotherapy treatment among both tumor and BAT samples. The metabolite patterns affected by treatment were different between tumor and BAT, both containing highly discriminating information, ROC values of 0.896 and 0.821, respectively. Our findings contribute to increased molecular knowledge of basic glioblastoma pathophysiology and point to the possibility of detecting metabolic marker patterns associated to early treatment response. PMID- 20302354 TI - Galactosylated poly(2-(2-aminoethyoxy)ethoxy)phosphazene/DNA complex nanoparticles: in vitro and in vivo evaluation for gene delivery. AB - To achieve efficient gene delivery to the tumor after intravenous administration, biodegradable poly(2-(2-aminoethyoxy)ethoxy)phosphazene (PAEP) was modified by lactobionic acid, bearing a galactose group as a targeting ligand. Galactosylated poly(2-(2-aminoethyoxy)ethoxy)phosphazene (Gal-PAEP) with 4.9% substitution degree of galactose could condense pDNA into nanoparticles with a size around 130 nm at the polymer/DNA ratio (N/P) of 2-40. For BEL-7402 cells, the in vitro transfection efficiency of gal-PAEP/DNA complex nanoparticles (gal-PACNs) was much higher than that of the PAEP/DNA complex nanoparticles (PACNs). MTT assay indicated that the cytotoxicity of PACNs significantly decreased after conjugating with the galactose moiety. Gal-PACNs displayed the selective gene expression in the tumor and liver with relatively low gene expression in the lung or other organs compared with PACNs. These results suggested that gal-PACNs could be a promising targeting gene carrier to deliver a therapeutic gene in future. PMID- 20302352 TI - Critical role of the isoform-specific region in alpha1-Na,K-ATPase trafficking and protein Kinase C-dependent regulation. AB - The isoform-specific region (ISR) is a region of structural heterogeneity among the four isoforms of the catalytic alpha-subunit of the Na,K-ATPase and an important structural determinant for isoform-specific functions. In the present study, we examined the role of a potential dileucine clathrin adaptor recognition motif [DE]XXXL[LI] embedded within the alpha1-ISR. To this end, a rat alpha1 construct where leucine 499 was replaced by a valine (as found in the alpha2 isoform sequence) was compared to wild-type rat alpha1 after stable expression in opossum kidney cells. Total Na,K-ATPase expression, activity, or in situ (86)Rb(+) transport was not affected by the L499V mutation. However, surface Na,K ATPase expression was nearly doubled. This increase was associated with a reduced rate of internalization from the cell surface of about 50% after a 4 h chase and became undetectable if clathrin-coated pit-mediated trafficking was blocked with chlorpromazine. Further, PKC-induced stimulation of Na,K-ATPase-mediated (86)Rb(+) uptake was doubled in mutant-expressing cells, comparable to the chimera containing the intact alpha2-ISR. Similar results were observed when the potential motif was disrupted by means of an E495S mutation. These findings suggest that a dileucine motif embedded within the Na,K-ATPase alpha1-ISR plays a critical role in the surface expression of Na,K-ATPase alpha1 polypeptides at steady state and in the response to PKC activation. PMID- 20302355 TI - Isocyano analogues of [Co(CO)(4)](n): a tetraisocyanide of cobalt isolated in three states of charge. AB - The encumbering m-terphenyl isocyanide ligand, CNAr(Mes2) (Mes = 2,4,6 Me(3)C(6)H(2)), is used to stabilize homoleptic tetraisocyanide complexes of cobalt in the 1-, 0, and 1+ charge state. Most importantly, these complexes serve as isolable analogues of the binary carbonyl complexes [Co(CO)(4)](-), Co(CO)(4), and [Co(CO)(4)](+). Sodium amalgam reduction of CoCl(2) in the presence of CNAr(Mes2) provides the salt Na[Co(CNAr(Mes2))(4)], which can be oxidized with 1 equiv of ferrocenium triflate (FcOTf) to the neutral complex, Co(CNAr(Mes2))(4). X-ray diffraction, FTIR spectroscopy, and low-temperature EPR spectroscopy reveal that Co(CNAr(Mes2))(4) modulates between D(2d)- and C(2v)-symmetric forms. DFT calculations are used to rationalize this structural modulation in terms of thermal access to low-energy b(2)-symmetric C-Co-C bending modes. Treatment of Na[Co(CNAr(Mes2))(4)] with 2 equiv of FcOTf, followed by addition of Na[BAr(F)(4)], provides the salt [Co(CNAr(Mes2))(4)]BAr(F)(4), which contains a diamagnetic, square planar monovalent cobalt center. The molecular and electronic structures of [Co(CNAr(Mes2))(4)]BAr(F)(4) are compared and contrasted to the reported properties of the carbonyl cation, [Co(CO)(4)](+). PMID- 20302356 TI - Is [FeO](2+) the active center also in iron containing zeolites? A density functional theory study of methane hydroxylation catalysis by Fe-ZSM-5 zeolite. AB - Arguments are put forward that the active alpha-oxygen site in the Fe-ZSM-5 catalyst consists of the FeO(2+) moiety. It is demonstrated that this zeolite site for FeO(2+) indeed obeys the design principles for high reactivity of the FeO(2+) moiety proposed earlier: a ligand environment consisting of weak equatorial donors (rather oxygen based than nitrogen based) and very weak or absent trans axial donor. The alpha-oxygen site would then owe its high reactivity to the same electronic structure features that lends FeO(2+) its high activity in biological systems, as well as in the classical Fenton chemistry. PMID- 20302357 TI - Formation and properties of organo-phosphatase complexes by abiotic and biotic polymerization of pyrogallol-phosphatase mixtures. AB - In this paper, the catalytic efficacy of peroxidase and manganese oxide, both commonly present in soil, to catalyze the formation of pyrogallol-phosphatase complexes was compared. The influence of several factors (e.g., the concentration of pyrogallol, the amount of catalysts, the nature of manganese oxide, birnessite, or pyrolusite, the incubation time, and the pH) on the transformation of pyrogallol and the characteristics and properties of the pyrogallol phosphatase interaction products were investigated. The pyrogallol transformation mediated by both catalysts was very fast and increased by increasing the catalyst concentration. The nature of the catalyst also influenced the size and the molecular mass of the formed complexes. When polymerization of pyrogallol occurred with high intensity, a loss of phosphatase activity occurred, and it strongly depended on the pH at which the process was carried out and the catalyst. In particular, with peroxidase, the phosphatase activity was much lower in either suspensions or supernatants and not measurable in the insoluble complexes as compared to that measured in the presence of manganese oxides. PMID- 20302358 TI - Antioxidant activity of wines determined by a polarographic assay based on hydrogen peroxide scavenge. AB - Antioxidant (AO) activity of various red and white wines of different origin as well as some individual phenolic compounds present in wine has been assessed using a polarographic assay. Direct current polarography has been used to survey hydrogen peroxide scavenge (HPS) upon gradual addition of tested samples. Results expressed as reciprocal value of wine volume required for 50% decrease of anodic limiting current of hydrogen peroxide have been validated through correlation with Folin-Ciocalteau and DPPH assays. All wines exhibit HPS activity analogous with total phenolic content and DPPH scavenge. Reliability and accuracy, low cost, and rapid and direct experimental procedure open a wide area for application of this assay, making it a good alternative to standard, widely accepted AO assays. PMID- 20302359 TI - Intramolecular anodic olefin coupling reactions: using competition studies to probe the mechanism of oxidative cyclization reactions. AB - A competition experiment was designed so that the relative rates of anodic cyclization reactions under various electrolysis conditions can be determined. Reactions with ketene dithioacetal and enol ether-based substrates that use lithium methoxide as a base were shown to proceed through radical cation intermediates that were trapped by a sulfonamide anion. Results for the oxidative coupling of a vinyl sulfide with a sulfonamide anion using the same conditions were consistent with the reaction proceeding through a nitrogen-radical. PMID- 20302360 TI - A straightforward three-component synthesis of alpha-amino esters containing a phenylalanine or a phenylglycine scaffold. AB - A range of alpha-amino esters has been synthesized in good to high yields using a straightforward three-component reaction among preformed or in situ generated aromatic or benzylic organozinc reagents, primary or secondary amines, and ethyl glyoxylate. The procedure, which is characterized by its simplicity, allows the concise synthesis of esters bearing a phenylglycine or a phenylalanine scaffold. PMID- 20302361 TI - Asymmetric acid-catalyzed Meerwein-Ponndorf-Verley-Aldol reactions of enolizable aldehydes. AB - A highly, stereo- and regioselective Meerwein-Ponndorf-Verley-Aldol etherification process of enolizable aldehydes is described. This new transformation is catalyzed by trifluoroacetic acid. The method also allows cross aldol reactions with alpha-branched enolizable aldehydes and thus provides access to defined configured quaternary stereogenic centers. PMID- 20302362 TI - Synthesis of polysubstituted furans based on a stepwise Sonogashira coupling of (Z)-3-iodoalk-2-en-1-ols with terminal propargylic alcohols and subsequent Au(I)- or Pd(II)-catalyzed cyclization-aromatization via elimination of H2O. AB - Recently, we have developed highly regio- and stereoselective carbometalation of 2-alkynols and 2,3-allenols. The organometallacyclic intermediates may be trapped with I(2) to afford 3-iodoalk-2-en-1-ols. These 3-iodoalk-2-en-1-ols may readily undergo the Sonogashira coupling with terminal propargyl alcohols to form 4-alkyn 2-ene-1,6-diols. Subsequent cycloisomerization in DMA or CH(2)Cl(2) with Au(PPh(3))Cl and AgOTf as the catalyst would afford polysubstituted 2-(1 alkenyl)furans; with PdCl(2) as the catalyst and the reaction in DMA in the presence of allylic bromides, the same substrates afforded polysubstituted 2-(1,4 alkadienyl)furans. In both types of catalyzed cyclization reactions, the elimination of H(2)O promoted the aromatization to form the furan ring. Different alkyl or aryl groups could be introduced into different positions of furans due to the substituent-loading capability of 3-iodoalkenols and diversity of the terminal propargyl alcohols and allylic bromides. PMID- 20302363 TI - Forecasting global generation of obsolete personal computers. AB - Electronic waste (e-waste) has emerged as a new policy priority around the world. Motivations to address e-waste include rapidly growing waste streams, concern over the environmental fate of heavy metals and other substances in e-waste, and impacts of informal recycling in developing countries. Policy responses to global e-waste focus on banning international trade in end-of-life electronics, the premise being that e-waste is mainly generated in the developed world and then exported to the developing world. Sales of electronics have, however, been growing rapidly in developing nations, raising the question of whether informal recycling in developing countries driven by international trade or domestic generation. This paper addresses this question by forecasting the global generation of obsolete personal computers (PCs) using the logistic model and material flow analysis. Results show that the volume of obsolete PCs generated in developing regions will exceed that of developed regions by 2016-2018. By 2030, the obsolete PCs from developing regions will reach 400-700 million units, far more than from developed regions at 200-300 million units. Future policies to mitigate the impacts of informal recycling should address the domestic situation in developing countries. PMID- 20302364 TI - Chlorine monoxide (Cl(2)O) and molecular chlorine (Cl(2)) as active chlorinating agents in reaction of dimethenamid with aqueous free chlorine. AB - HOCl is often assumed to represent the active oxidant in solutions of free available chlorine (FAC). We present evidence that Cl(2)O and Cl(2) can play a greater role than HOCl during chlorination of the herbicide dimethenamid. Reaction orders in [FAC] were determined at various solution conditions and ranged from 1.10 +/- 0.13 to 1.78 +/- 0.22, consistent with the concurrent existence of reactions that appear first-order and second-order in [FAC]. Solution pH, [Cl(-)], [FAC], and temperature were systematically varied so that the reactivity and activation parameters of each FAC species could be delineated. Modeling of kinetic data afforded calculation of second-order rate constants (units: M(-1) s(-1)) at 25 degrees C: k(Cl2O) = (1.37 +/- 0.17) x 10(6), k(Cl2) = (1.21 +/- 0.06) x 10(6), and k(HOCl) = 0.18 +/- 0.10. Under conditions typical of drinking water chlorination, Cl(2)O is the predominant chlorinating agent of dimethenamid. To the extent that Cl(2)O represents the active species in reactions with other disinfection byproduct (DBP) precursors, the influence of [FAC] and pH on DBP precursor reaction rates is different than if HOCl were the principal oxidant. Moreover, these findings call into question the validity of apparent rate constants (k(app)) commonly reported in the chlorination literature. PMID- 20302365 TI - s-Tetrazines as building blocks for new functional molecules and molecular materials. PMID- 20302366 TI - How PCBs are like grasshoppers. PMID- 20302367 TI - Environmental assessment of the CIESOL solar building after two years operation. AB - Life cycle assessment is applied to assess the environmental benefits and trade offs of a solar-assisted heating, ventilating, and air-conditioning (HVAC) system installed in the CIESOL building in Almeria (southeastern Spain). The environmental performance of this system is compared to that of a conventional HVAC system using a heat pump. The study evaluates these systems from cradle to grave, and the impact assessment includes, in addition to the CML2001 method, an impact category dealing with impacts on freshwater resources. The results show that the solar-assisted HVAC involves lower impacts in many impact categories, achieving, as an example, a reduction of 80% in greenhouse-gas emissions. On the other hand, key weak points of this system are the production of capital goods, but specially water use for cooling, due to its high impact on freshwater resources. Minimization of water requirements should be a priority for further development of this promising technology. PMID- 20302368 TI - The active species in drinking water chlorination: the case for Cl(2)O. PMID- 20302369 TI - Effects of chitosan and rosmarinate esters on the physical and oxidative stability of liposomes. AB - Liposomes have substantial potential to deliver bioactive compounds in foods. However, the oxidative degradation and physical instability of liposomes limit their utilization. This research evaluated the ability of chitosan and rosmarinic acid and its esters to increase the physical and oxidative stability of liposomes. Particle size analysis studies showed that the physical stability of liposomes was enhanced by depositing a layer of cationic chitosan onto the negatively charged liposomes. The combination of octadecyl rosmarinate (40 microM) and chitosan coating resulted in significantly greater inhibition of lipid oxidation in the liposomes compared to chitoson or octadecyl rosmarinate alone. Increasing the concentrations of octadecyl rosmarinate to a concentration of 40 microM in the chitosan-coated liposomes decreased lipid oxidation. Only butyl rosmarinate exhibited stronger antioxidant activity than free rosmarinic acid. Eicosyl rosmarinate (20 carbons) had lower antioxidant activity than all other rosmarinic acid derivatives. These results suggest that by combining the inclusion of appropriate antioxidants such as rosmarinic acid and the deposition of a chitosan coating onto the surface of liposomes may significantly increase the oxidative and physical stability of liposomes. PMID- 20302370 TI - Phenolic compounds in cherry ( Prunus avium ) heartwood with a view to their use in cooperage. AB - The phenolic and tannic composition of heartwood extracts from Prunus avium , commonly known as cherry tree, before and after toasting in cooperage were studied using HPLC-DAD and HPLC-DAD/ESI-MS. Nonflavonoid (16 compounds) and flavonoid (27 compounds) polyphenols were identified, 12 of them in only a tentative way. The nonflavonoids found were lignin constituents, and their pattern is different compared to oak, since they include compounds such as protocatechuic acid and aldehyde, p-coumaric acid, methyl vanillate, methyl syringate, and benzoic acid, but not ellagic acid, and only a small quantity of gallic acid. In seasoned wood we found a great variety of flavonoid compounds which have not been found in oak wood for cooperage, mainly, in addition to the flavan-3-ols (+)-catechin, a B-type procyanidin dimer, and a B-type procyanidin trimer, the flavanones naringenin, isosakuranetin, and eriodictyol and the flavanonols aromadendrin and taxifolin. Seasoned and toasted cherry wood showed different ratios of flavonoid to nonflavonoid compounds, since toasting results in the degradation of flavonoids, and the formation of nonflavonoids from lignin degradation. On the other hand, the absence of hydrolyzable tannins in cherry wood, which are very important in oak wood, is another particular characteristic of this wood that should be taken into account when considering its use in cooperage. PMID- 20302371 TI - Pharmacokinetics of adenosine and cordycepin, a bioactive constituent of Cordyceps sinensis in rat. AB - Cordycepin is a bioactive constituent of Cordyceps sinensis that has been shown to regulate homeostatic function. As an adenosine analogue, it is possible cordycepin goes through a similar metabolic pathway to that of adenosine. To investigate this hypothesis, a sensitive liquid chromatography with photodiode array detector (HPLC-PDA) coupled to a microdialysis sampling system was developed to monitor cordycepin and adenosine in rat blood and liver. Other endogenous nucleosides were simultaneously measured to further understand the downstream metabolic pathway. The experiments were divided into six parallel groups for drug administration: (1) normal saline vehicle, (2) adenosine, (3) cordycepin, (4) normal saline + erythro-9-(2-hydroxy-3-nonyl)adenine (EHNA; a potent adenosine deaminase inhibitor), (5) adenosine + EHNA, and (6) cordycepin + EHNA. The pharmacokinetic results suggest that the levels of both adenosine and cordycepin decreased rapidly in blood around 30 min after drug administration. When adenosine was given, the concentrations of adenosine metabolites, hypoxanthinosine and hypoxanthine, increased in rat blood. This phenomenon was inhibited by EHNA pretreatment. An unidentified peak was observed in the blood and liver samples after cordycepin administration. The decline of this unidentified peak paralleled the decreased of the concentration of cordycepin, and it was not observed in the presence of the adenosine deaminase inhibitor. It is concluded that adenosine and cordycepin had short elimination half-lives and high rates of clearance and their biotransformation was suppressed by EHNA. PMID- 20302372 TI - Fractionation of alkali-solubilized hemicelluloses from delignified Populus gansuensis: structure and properties. AB - The dewaxed cell walls of Populus gansuensis were delignified with NaClO(2) and then sequentially extracted with 0.25, 0.5, and 1.0 M KOH under a solid to liquid ratio of 1: 25 (g mL(-1)) at 25 degrees C for 10 h. The successive treatments together resulted in the dissolution of 83.7% of original hemicelluloses. The solubilized hemicellulosic fractions were further fractionated into six hemicellulosic subfractions by an iodine-complex precipitation technique. Their chemical and physical characteristics were determined by HPAEC, GPC, FT-IR, and (1)H and (13)C NMR spectroscopy. Neutral sugar composition and molecular weight analysis showed that, for each extract, the hemicellulosic subfractions that precipitated with aqueous potassium iodide-iodine had lower overall uronic acid/xylose (Uro/Xyl) ratios and higher molecular weights (M(w)) than those remaining in the solution. FT-IR, (1)H, and (13)C NMR spectroscopy analysis indicated that the alkali-soluble hemicelluloses of Populus gansuensis had a structure composed of the (1 --> 4)-linked beta-D-xylopyranosyl backbone with 4-O methyl-alpha-D-glucuronic acid attached to O-2 of the xylose residues. PMID- 20302373 TI - Neurotrophic and cytoprotective action of luteolin in PC12 cells through ERK dependent induction of Nrf2-driven HO-1 expression. AB - Luteolin (3',4',5,7-tetrahydroxyflavone), a food-derived flavonoid, has been reported to possess antioxidant, anti-inflammatory, and anticancer activities. In this work, we assessed whether luteolin has neurotrophic activity, namely, the ability to induce neurite outgrowth and to attenuate serum withdrawal-induced cytotoxicity in PC12 cells. Our results show that luteolin significantly induced neurite outgrowth along with increased expression of the differentiation marker, growth-associated protein-43 (GAP-43), in PC12 cells dose-dependently. Incubation of serum-deprived PC12 cells with luteolin prevented apoptosis, increased the expression of heme oxygenase-1 (HO-1) mRNA and protein levels, and enhanced the binding of nuclear factor E2-related factor 2 (Nrf2) to antioxidant response element (ARE), which works as an enhancer sequence in the HO-1 promoter. Addition of zinc protoporphyrin (Znpp), a selective HO-1 competitive inhibitor, significantly reduced the cytoprotective ability of luteolin, indicating the vital role of HO-1. Luteolin also persistently activated extracellular signal regulated protein kinase 1/2 (ERK1/2); while the addition of U0126, a pharmacological MEK/ERK inhibitor, attenuated luteolin-induced Nrf2 binding activity, HO-1 expression, cytoprotective effect, and neurite outgrowth. Taken together, the above findings suggest that luteolin induces neurite outgrowth and augments cellular antioxidant defense capacity, at least in part, through the activation of the ERK signaling pathway. PMID- 20302374 TI - Effects of management factors on the concentration of a high molecular weight polysaccharide fraction from log-grown shiitake mushrooms (Lentinula edodes (Berk.) Pegler). AB - Shiitake mushrooms have a reputation as a healthy food. Growers may be able to use the presence of health-promoting constituents as a marketing tool to promote sales of their products for premium prices. There are few reports on the effects of management protocols for log-grown shiitakes on the concentrations of constituents to guide growers. This paper summarizes several studies that examined the effects of shiitake strains, mushroom cap development, and length of saprophytic association on the concentrations of a high molecular weight polysaccharide fraction that includes lentinan (HMWP). Concentrations of HMWP in mushrooms varied as much as 8-fold during fruiting among the 12 strains tested in these studies. Results also indicate that the concentrations of HMWP in shiitake mushrooms are influenced by the fungal phenotype and the characteristics of the environment. General trends showed that (1) mushrooms harvested at more immature stages of development (during bud break or before veil break) tended to have higher concentrations of HMWP and (2) the initial harvests of mushrooms from an inoculated log tend to have higher concentrations of HMWP than subsequent harvests. Results suggest that growers interested in maximizing the HMWP content of their mushrooms should use shiitake strains NN-430 and 569-430. PMID- 20302375 TI - The impact of genotype and salinity on physiological function, secondary metabolite accumulation, and antioxidative responses in lettuce. AB - Salinity inhibits plant growth due to osmotic and ionic effects. However, little is known about the impact of genotype and salinity on biochemical and molecular processes in the leafy vegetable lettuce. We report here evaluations of two lettuce types, Verte (NaCl tolerant) and Romaine (NaCl sensitive), under iso osmotic 100 mM NaCl and 77 mM Na(2)SO(4) treatments. As compared to Romaine, NaCl treated Verte displayed better growth, contained lower levels of inorganic cations in leaves, and possessed superior antioxidative capacity due to enhanced carotenoid and phenolics biosynthesis and more active antioxidative enzymes resulting in reduced membrane damage. Both genotypes had relatively similar growth patterns under Na(2)SO(4) treatment, but Romaine showed enhanced root lignification, greater malondialdehyde formation, and suppressed Fe-superoxide dismutase expression in roots as compared with Verte. PMID- 20302377 TI - Lipoic acid: an immunomodulator that attenuates glycinin-induced anaphylactic reactions in a rat model. AB - The purpose of this study was to evaluate the attenuation effects of consuming a small dose of lipoic acid on soybean glycinin-induced hypersensitivity using a rat model. Sensitized by gavage with glycinin, weaned rats were orally supplemented with the diet containing 12.5 mug of lipoic acid/g (per diet). Results showed that untreated, sensitized rats demonstrated an increase in the level of serum IgE, the level of histamine release, and incidence of diarrhea and reduced growth performance compared with the controls (P < 0.05). Lipoic acid significantly (P < 0.05) improved growth performance while reducing mast cell numbers, the level of serum IgE, and the level of histamine release. Lipoic acid supplementation altered the balance of cytokines, attenuated the Th2-type immune response, and amended the ratio of CD4(+) to CD8(+) T cells (P < 0.05). Our results suggest that a small dose of lipoic acid has the potential to be an immunomodulator to prevent soybean-induced allergies. PMID- 20302378 TI - Comparison of different strategies for soybean antioxidant extraction. AB - Three extraction strategies including Soxhlet extraction, conventional solid liquid extraction, and ultrasonic-assisted extraction (UAE) were compared for their efficiency to extract phenolic antioxidants from Virginia-grown soybean seeds. Five extraction solvents were evaluated in UAE and the conventional extraction. The soybean extracts were compared for their total phenolic contents (TPC), oxygen radical absorbance capacity (ORAC), and 2,2-diphenyl-1 picrylhydrazyl radical (DPPH(*)) scavenging activities. The results showed that UAE improved the extraction of soybean phenolic compounds by >54% compared to the conventional and Soxhlet extractions. Among the tested solvents, 50% acetone was the most efficient for extracting soybean phenolic compounds. There was no significant correlation between the TPC and antioxidant activities of the soybean extracts. The extracts prepared by 70% ethanol had the highest ORAC values. Overall, UAE with 50% acetone or 70% ethanol is recommended for extracting soybean antioxidants on the basis of the TPC and ORAC results. PMID- 20302376 TI - First principles insight into the alpha-glucan structures of starch: their synthesis, conformation, and hydration. PMID- 20302379 TI - Direct chiral resolution of metalaxyl and metabolite metalaxyl acid in aged mobile phases: the role of trace water. AB - The separation of chiral transformation products greatly complements the understanding of the stereochemistry of chiral pollutants. In this study, direct enantiomeric resolution of metalaxyl and its main degradation product metalaxyl acid, often co-occurring in the environment, was carried out in normal-phase high performance liquid chromatography with a Chiralcel OJ-H column. (R)-Metalaxyl acid and (S)-metalaxyl, which were almost parallel bonding to the chiral stationary phase, tended to separate, started to overlap, coeluted, and separated again with subtle changes of the mobile phase consisting of n-hexane, 2-propanol, acetic acid, and trace water. Their competition above hampered an acceptable direct separation in fresh mobile phases. Aged mobile phases with a storage period of 3-5 days, however, significantly improved their separation, in which trace water from moisture air diffusion was found to play a major role. Trace water differentially affected peak width and retention times and then induced enhanced peak separation, confirmed by deliberate addition of water to fresh mobile phases. Furthermore, none of the studied factors, involving temperature, concomitant analytes, and trace water, could cause changes of the configuration of the chiral stationary phase. Simultaneous enantiomeric separation of both compounds was achieved in aged or fresh mobile phases with adventitious or added water and gave satisfactory peak separation, all with Rs values of more than 1.20 in environmental samples. PMID- 20302380 TI - Contribution of chlorogenic acids to the inhibition of human hepatic glucose-6 phosphatase activity in vitro by Svetol, a standardized decaffeinated green coffee extract. AB - Glucose-6-phosphatase (Glc-6-Pase) is a multicomponent system that exists primarily in the liver and catalyzes the terminal step in gluconeogenesis and glycogenolysis. Several studies have attempted to identify synthetic or natural compounds that inhibit this enzyme complex for therapeutic use in regulating blood glucose and type 2 diabetes. For this paper an in vitro structure-activity relationship study of several natural chlorogenic acids was conducted, and the active components of the natural decaffeinated green coffee extract Svetol were identified. Glucose-6-phosphate (Glc-6-P) hydrolysis was measured in the presence of Svetol or chlorogenic acids in intact human liver microsomes. Svetol significantly inhibited Glc-6-P hydrolysis in intact human liver microsomes in a competitive manner, and it was determined that chlorogenic acids (caffeoylquinic acids and dicaffeoylquinic acids) were the chief compounds mediating this activity. In addition, the structure-activity analysis showed that variation in the position of the caffeoyl residue is an important determinant of inhibition of Glc-6-P hydrolysis. This inhibition by Svetol contributes to its antidiabetic, glucose-lowering effects by reducing hepatic glucose production. PMID- 20302381 TI - Total synthesis of proposed auranthine. AB - Starting from CBz-protected glutamic anhydride and Boc-protected o-aminobenzyl amine, the first total synthesis of proposed structure of auranthine has been reported. An intramolecular aza-Wittig reaction involving a lactam carbonyl group that delivered the diazepine core unit was the key step in the synthesis. PMID- 20302382 TI - Facile synthesis of 3-nitro-2-substituted thiophenes. AB - A new approach to 3-nitro-2-substituted thiophenes has been developed. Exposure of commercially available 1,4-dithane-2,5-diol to nitroalkenes in the presence of 20% triethylamine results in a tandem Michael-intramolecular Henry reaction to form the corresponding tetrahydrothiophene. Subsequent microwave irradiation on acidic alumina in the presence of chloranil effects the solvent free dehydration and aromatization to form 3-nitro-2-substituted thiophenes cleanly and rapidly. A simple workup procedure removes the requirement for purification by chromatography in most cases. PMID- 20302383 TI - Effect of solvent and temperature on the lithium-bromine exchange of vinyl bromides: reactions of n-butyllithium and t-butyllithium with (E)-5-bromo-5 decene. AB - The outcome of reactions of (E)-5-bromo-5-decene (1), a representative vinyl bromide, with t-BuLi or n-BuLi at 0 degrees C and room temperature, respectively, in a variety of solvent systems has been investigated. Vinyl bromide 1 does not react with t-BuLi in pure heptane; however, the presence of even small quantities of an ether in a predominantly heptane medium resulted in virtually complete consumption of 1 at 0 degrees C, resulting in nearly the same distribution of products, including 60-80% of (Z)-5-decenyllithium, regardless of the solvent composition. Vinyl bromide 1 reacts slowly with n-BuLi at room temperature in a variety of ether and heptane-ether mixtures to afford a mixture of products including significant quantities of recovered starting material. The results of these experiments demonstrate that lithium-bromine exchange between a vinyl bromide and either t-BuLi or n-BuLi at temperatures significantly above -78 degrees C is not an efficient method for the generation of a vinyllithium. PMID- 20302384 TI - Self-assembly behavior of colistin and its prodrug colistin methanesulfonate: implications for solution stability and solubilization. AB - Colistin is an amphiphilic antibiotic that has re-emerged into clinical use due to the increasing prevalence of difficult-to-treat Gram-negative infections. The existence of self-assembling colloids in solutions of colistin and its derivative prodrug, colistin methanesulfonate (CMS), was investigated. Colistin and CMS reduced the air-water interfacial tension, and dynamic light scattering (DLS) studies showed the existence of 2.07 +/- 0.3 nm aggregates above 1.5 mM for colistin and of 1.98 +/- 0.36 nm aggregates for CMS above 3.5 mM (mean +/- SD). Above the respective critical micelle concentrations (CMC) the solubility of azithromycin, a hydrophobic antibiotic, increased approximately linearly with increasing surfactant concentration (5:1 mol ratio colistin:azithromycin), suggestive of hydrophobic domains within the micellar cores. Rapid conversion of CMS to colistin occurred below the CMC (60% over 48 h), while conversion above the CMC was less than 1%. The formation of colistin and CMS micelles demonstrated in this study is the proposed mechanism for solubilization of azithromycin and the concentration-dependent stability of CMS. PMID- 20302385 TI - The impact of telemedicine on quality of life in rural areas: the Extremadura model of specialized care delivery. AB - BACKGROUND: Referrals from rural health centers to urban hospitals join waiting lists as outpatients for hospital admission and hospital treatment. This influences quality of life (QoL) of the rural population and retired people who require medical attention without traveling, provided no risks are involved. For this reason, a rural region of Spain has adopted a strategy to deliver telemedicine (TM) specialized care (Extremadura model) as a political decision. OBJECTIVES: The present study aimed at objectively assessing QoL on aspects of health and well-being for citizens benefiting from this system. METHODS: We performed a randomized study of 800 primary care patients referred for specialized care: 420 regular face-to-face hospital referrals and 380 referred to a hospital specialist at a distance by TM. The study used two questionnaires: a modified version of the classical SF-12v2 short form questionnaire for health and well-being and a specific author-elaborated questionnaire. The latter focused on major patient concerns such as (1) discomfort and pain relief, (2) swift diagnosis, (3) swift treatment, (4) swift decision on hospital admission or not, (5) avoidance of traveling, (6) avoidance of red tape, and (7) personal attention. QoL was assessed twice: before referral to a hospital specialist and 6 months after referral to the same. The results were statistically compared. RESULTS: Both groups showed comparable health status with added advantages for TM referrals such as (1) less traveling (p = 0.0001) and (2) faster diagnosis, health examination, and treatment (p = 0.0001). CONCLUSION: Telemedicine care by a hospital specialist through videoconferencing was comparable to hospital referral for face-to-face medicine. Teleconsultations managed by nurses had a positive impact on the QoL of rural patients. They did not have to travel and thus diagnoses and examinations to start treatment were initiated faster. PMID- 20302387 TI - Refractory cytopenia with unilineage dysplasia: analysis of prognostic factors and survival in 126 patients. AB - According to the revised WHO classification of 2008, dysplasia in > or = 10% of one bone marrow lineage and one cytopenia constitutes the low-risk category of unilineage cytopenia and unilineage dysplasia (UCUD). We retrospectively reclassified, according to WHO, low-risk MDS from our database and found 126 subjects with these features at diagnosis: 79 patients were categorized as refractory anemia (RA), 23 patients as refractory neutropenia (RN), and 24 as refractory thrombocytopenia (RT). We did not find differences between the three subgroups as regards sex, median age, and cytogenetic aberrations. Lower PMN count (0.8 x 10(9)/L) was observed in the RN category, as well as lower platelet count in the RT category (51 x 10(9)/L). Moreover, we found a lower rate of patients requiring RBC transfusions, during the disease course, in the RT category (45.8%) as compared to RA (62%) and RN (69%) groups (p = 0.05); a lower incidence of infections at diagnosis in the RT category (20.8%) compared to RA (32%) and RN (43%) categories (p = 0.03); and a higher incidence of hemorrhagic symptoms at diagnosis in the RT category (41.6%) and RN category (26%) as compared to the RA group (5%) (p = 0.001). Application of different scoring systems (Bournemouth and Spanish scores, WPSS) revealed a low OS in high-risk patients within the RT category, compared to RA and RN categories, although unlikely to reflect the consequences of low OS found in the former category. Statistically significant differences were also evidenced in the incidence of acute myeloid leukemia (AML) evolution and overall survival: 7/79 (8%) patients with the RA category evolved to AML in a median time of 89 months, whereas 4/23 (17%) of the RN category and 1/24 (4%) of the RT category experienced disease progression, in a median time of 33.8 and 12.8 months, respectively (p = 0.03). The RT category had a lower overall survival (15.9 months) as compared to RA (48.2 months) and RN (35.9 months) categories (p < 0.001). In conclusion, in our study, application of the revised 2008 WHO classification confirmed the importance of separating patients with unilineage dysplasia for prognostic disease assessment; from our results it seems that the RT category has a worse outcome. PMID- 20302386 TI - Treatment of autoimmune cytopenia complicating progressive chronic lymphocytic leukemia/small lymphocytic lymphoma with rituximab, cyclophosphamide, vincristine, and prednisone. AB - Treatment of autoimmune cytopenia complicating progressive chronic lymphocytic leukemia (CLL) is constrained by intolerance of myelosuppression and the risk of exacerbation of autoimmune cytopenia by purine analogs particularly when used as single agents. We report on 20 such patients treated with rituximab, cyclophosphamide, vincristine, and prednisone (R-CVP). Autoimmune cytopenia responded in 19 patients (14 complete remissions (CR), five partial remissions (PR)) with a median time to next treatment (TTT) for autoimmune cytopenia of 21.7 months. Progressive CLL responded in 17 patients (nine CR/complete clinical response, eight PR) with a median TTT of 27.7 months. Five patients have not required any re-treatment at 15-30 months. Grade 3-4 toxicities were infections (n = 3) and drug-induced pneumonitis (n = 1). No patient required blood cell transfusions after cycle 1 of therapy. We conclude that R-CVP is effective and tolerable therapy for autoimmune cytopenia complicating progressive CLL, but the duration of response is suboptimal. PMID- 20302388 TI - Dasatinib and nilotinib in imatinib-resistant Philadelphia-positive chronic myelogenous leukemia: a 'head-to-head comparison'. AB - Imatinib has revolutionized the treatment of patients with chronic myeloid leukemia (CML). However, some patients may experience resistance or intolerance to imatinib over time. For these patients, two excellent therapeutic options are available. Dasatinib, approved in 2006 for the treatment of patients with CML in all phases who experience imatinib resistance or intolerance, has displayed significant efficacy, with a 2-year follow-up showing durable hematologic and cytogenetic responses, as well as prolonged progression-free and overall survival. Nilotinib was approved in 2007 for the treatment of patients with CML in chronic phase or CML in accelerated phase, resistant or intolerant to prior therapy including imatinib, based on strong efficacy as well as a favorable safety profile. Several factors, including mutation status, patient history, and existing comorbidities can impact the decision to use dasatinib or nilotinib, or pursue other options such as allogeneic stem cell transplant. The purpose of this review article is to shed light on a further consideration when deciding which agent to use, based on the efficacy and safety of dasatinib and nilotinib. This consideration involves the differences in both the imatinib-resistant and intolerant patients enrolled in the pivotal studies for each agent, as well as other trial criteria. PMID- 20302389 TI - Editorial. Brainstem cavernomas. PMID- 20302390 TI - Factors predicting language lateralization in patients with perisylvian vascular malformations. Clinical article. AB - OBJECT: The authors conducted a study to determine the factors associated with right-sided language dominance in patients with cerebrovascular malformations. METHODS: Twenty-two patients with either arteriovenous malformations (AVMs [15 cases]) or cavernous malformations (7 cases) underwent functional MR (fMR) imaging studies of language function; a 3.0-T head-only unit was used. Lateralization indices were calculated separately for Broca and Wernicke areas. Lesion size, Spetzler-Martin grade, and the distance between the lesion and anatomically defined language cortex were calculated for each patient. RESULTS: Right-sided language dominance occurred in 5 patients, all of whom had AVMs within 10 mm of canonical language areas. Three patients had right-sided language dominance in the Wernicke area alone whereas 2 had right-sided language dominance in both Broca and Wernicke areas. Wada testing and intraoperative electrocortical stimulation were performed as clinically indicated to corroborate fMR imaging findings. CONCLUSIONS: The primary factor associated with right-sided language dominance was the AVM being within 10 mm of anatomically defined language areas. The lesion size and the Spetzler-Martin grade were not significant factors. Anomalous fMR imaging laterality was typically confined to the language area proximate to the lesion, with the distal language area remaining in the left hemisphere dominant. This study emphasizes the need to map each case individually in patients with left perisylvian AVMs. Assumptions about eloquent cortex based on anatomical landmarks (a key component of Spetzler-Martin grading) may have to be reconsidered. PMID- 20302391 TI - Prognostic significance of contrast-enhancing anaplastic astrocytomas in adults. AB - OBJECT: Patients harboring anaplastic astrocytomas (AAs) typically have a poor prognosis, with median survival times of approximately 3 years following resection. However, a significant variability in individual outcomes remains, with some patients surviving for a few months and others for several years. The ability to predict patient outcomes based on preoperative variables would help prognosticate survival and may also guide treatment strategies. The prognostic implications of a preoperative contrast-enhancing AA remain poorly understood. METHODS: The medical records of all patients who underwent a craniotomy for a hemispheric AA from 1996 to 2006 at a single institution were retrospectively reviewed. Multivariate proportional hazards regression analysis was used to identify independent associations with recurrence and survival. The Kaplan-Meier method and log-rank analysis were used to plot and compare outcomes for patients with and without preoperative contrast enhancement. RESULTS: One hundred sixty five patients were available for analysis. The AAs were contrast enhancing in 102 patients (62%), and nonenhancing in 63 patients (38%). There were no significant differences in clinical and treatment-related variables between patients with and without contrast enhancement. After multivariate analysis, contrast enhancement was independently associated with decreased survival (p = 0.02) and increased recurrence (p = 0.04). The 5-year overall survival rates for patients with contrast-enhancing versus nonenhancing tumors were 31 and 38.5%, respectively. The 3-year rates of progression-free survival for patients with contrast enhancing versus nonenhancing tumors were 32 and 56%, respectively. Interestingly, heterogeneously enhancing tumors appear to result in poorer outcomes as compared with other types of enhancement (such as ring enhancing, nodular, and others). Among patients with contrast-enhancing AAs, gross-total resection significantly delayed recurrence (p = 0.05) but did not significantly prolong survival (p = 0.52). CONCLUSIONS: This study may provide insights into risk-stratifying patients with AAs, and most specifically those with AAs that enhance with contrast administration. PMID- 20302392 TI - Regional vascular relationships to the foramen ovale: an anatomical study with application to approaches to the external skull base with an emphasis on transcutaneous procedures for the treatment of trigeminal neuralgia. AB - OBJECT: The foramen ovale and its neighboring vascular structures may be seen via external approaches to the skull base. More commonly, however, transcutaneous approaches to the foramen ovale are performed. Although complications with this latter technique are uncommon, studies of the distances to the surrounding extracranial vascular structures are lacking in the literature. The present study aimed to elucidate such anatomical relationships. METHODS: Twenty adult cadavers (40 sides) underwent dissection of the region surrounding the foramen ovale at the external skull base. Measurements between the external surface of the foramen ovale and surrounding vascular structures were made. RESULTS: From the nearest aspect of the undersurface of the foramen ovale, the authors found that the mean distances to the middle meningeal artery, maxillary artery, superior bulb of the internal jugular vein, and internal carotid artery at its entrance to and exit from the carotid canal were 3, 19, 20, 9, and 12 mm, respectively. Distances tended to be shorter in females, but this did not reach statistical significance. On the basis of these data, the authors also determined a safe zone while approaching the undersurface of the foramen ovale. CONCLUSIONS: Additional knowledge of the neurovascular relationships surrounding the foramen ovale may be useful to the neurosurgeon and may help decrease the potential for complications. PMID- 20302393 TI - Quality of life in neurooncology--age matters. AB - OBJECT: Due partly to therapeutic improvements and prolonged patient survival, the field of neurooncology is gradually undergoing a philosophical shift, progressively moving toward a more functional approach to patient welfare. This shift includes, as one of its defining objectives, the promotion of elevated levels of quality of life (QOL) and quality of health (QOH) for patients of all ages. Unfortunately, an adult life-stage perspective has never been used to study the long-lasting impact of age on well-being in neurooncology patients. METHODS: In this study, the authors assessed and compared the QOL and QOH scores of 42 younger adults (< or = 40 years of age) and 88 older adults (> 40 years of age) presenting with a primary supratentorial tumor. RESULTS: After having controlled for biomedical and treatment-related factors, the authors discovered that older adults reported lower functional well-being and poorer neurocognitive functioning than younger adults. This age difference appeared earlier than expected (developing as early as middle age), suggesting an accelerated effect of disease on the aging process. Importantly, it was also found that the variables that predict QOL and QOH differed depending on patient age. For example, support from friends was a significant predictor of QOL for younger adults, whereas the capacity to continue enjoying life was a significant predictor for older adults. Moreover, the presence of a high-grade tumor and increased physical pain had a negative impact on the QOH of younger adults, whereas increased difficulty with concentration negatively impacted the QOH of older adults. CONCLUSIONS: These age differences clearly warn against consolidating the QOL or QOH scores of younger and older adults, and instead suggest that age at diagnosis is essential when considering patient perspective, and when establishing tailored support programs. PMID- 20302394 TI - The presigmoid approach to anterolateral pontine cavernomas. Clinical article. AB - OBJECT: Anterolateral cavernomas of the pons have been surgically removed via a variety of approaches, commonly retrosigmoid or transventricular. The goal in this study was to evaluate the presigmoid approach as an alternative. METHODS: Clinical data were reviewed in 9 patients presenting with anterolateral pontine cavernomas between 1999 and 2007. RESULTS: All patients were treated via a presigmoid approach, which provided a nearly perpendicular trajectory to the anterolateral pons. The brainstem was entered through a "safe zone" between the trigeminal nerve and the facial/vestibulocochlear nerve complex. Complete resection was achieved in all cases. No patient experienced recurrent events during follow-up (1-24 months). The patients' modified Rankin Scale score improved within 1 year of surgery (1.7 +/- 0.4) compared with baseline (2.6 +/- 0.2; p < 0.05). Only one patient experienced a new deficit (decreased hearing), which was corrected with a hearing aid. CONCLUSIONS: The presigmoid approach is recommended for the resection of anterolateral pontine cavernomas. With this approach, the need for cerebellar retraction is nearly eliminated. The lateral "presigmoid" entry point creates a trajectory that allows complete resection of even deep lesions at this level, or anterior to the internal acoustic meatus. PMID- 20302395 TI - Skin-derived precursors differentiating into dopaminergic neuronal cells in the brains of Parkinson disease model rats. AB - OBJECT: In the authors' previous study, they observed that amino acids 157-171 of von Hippel-Lindau protein (VHL peptide) induced neuronal differentiation of skin derived precursors. They also noted that transplantation of these differentiated cells into the striata of a Parkinson disease (PD) rat model reduced apomorphine induced rotations. In the present study, they investigated if these cells produce dopamine in the striatum. METHODS: Skin-derived precursors were differentiated into neurons using VHL peptide and transplanted into the striata of a PD model of rats. Four weeks after transplantation, a probe was inserted into rat striata and extracellular dopamine was extracted by microdialysis. Dopamine levels were measured by high-pressure liquid chromatography. Brain sections were assessed by immunohistochemical analysis for the presence of tyrosine hydroxylase and dopamine transporter. RESULTS: Increased dopamine levels in the striata of the rats were observed after transplantation (p < 0.01), and these were correlated with a reduction in the number of apomorphine-induced rotations (p < 0.05). Skin derived precursors observed along the tract of transplantation were positive for tyrosine hydroxylase and dopamine transporter. CONCLUSIONS: This study suggests that transplantation of skin-derived precursors, differentiated into neuronal cells using VHL peptide, can improve PD-like symptoms by enabling production of dopamine in the striata in a PD model of rats. PMID- 20302396 TI - Methylated N-(4-N,N-dimethylaminocinnamyl) chitosan enhances paracellular permeability across Caco-2 cells. AB - The effect of methylated N-(4-N,N-dimethylaminocinnamyl) chitosan (TM-CM-CS) was investigated on paracellular permeability and its toxicity towards Caco-2 cells. Fluorescein isothiocyanate dextran 4,400 (FD-4) was used as the model compound for paracellular transport. The factors, i.e. the degree of quaternization (DQ) and the extent of N-substitution (ES) of the derivatives, were studied for the effect on transepithelial electrical resistance (TEER) and permeability. The results revealed that at pH 7.4, TM-CM-CS appeared to increase cell permeability in a dose-dependent manner, and the effect was relatively reversible at lower doses of 0.05-0.5 mM. The difference of the DQ and the ES of TM-CM-CS slightly affected the decrease of TEER values and the FD-4 permeability. The cytotoxicity of TM-CM-CS was concentration-dependent and did not cause an acute cytotoxic effect as analyzed by the MTT assay. These studies demonstrated that this novel modified chitosan has the potential to be used as an intestinal absorption enhancer of therapeutic macromolecules. PMID- 20302399 TI - Measurement of coronary flow response to cold pressor stress in asymptomatic women with cardiovascular risk factors using spiral velocity-encoded cine MRI at 3 Tesla. AB - BACKGROUND: Coronary sinus (CS) flow in response to a provocative stress has been used as a surrogate measure of coronary flow reserve, and velocity-encoded cine (VEC) magnetic resonance imaging (MRI) is an established technique for measuring CS flow. In this study, the cold pressor test (CPT) was used to measure CS flow response because it elicits an endothelium-dependent coronary vasodilation that may afford greater sensitivity for detecting early changes in coronary endothelial function. PURPOSE: To investigate the feasibility and reproducibility of CS flow reactivity (CSFR) to CPT using spiral VEC MRI at 3 Tesla in a sample of asymptomatic women with cardiovascular risk factors. MATERIAL AND METHODS: Fourteen asymptomatic women (age 38 years +/- 10) with cardiovascular risk factors were studied using 3D spiral VEC MRI of the CS at 3 T. The CPT was utilized as a provocative stress to measure changes in CS flow. CSFR to CPT was calculated from the ratio of CS flow during peak stress to baseline CS flow. RESULTS: CPT induced a significant hemodynamic response as measured by a 45% increase in rate-pressure product (P<0.01). A significant increase in CS volume flow was also observed (baseline, 116 +/- 26 ml/min; peak stress, 152 +/- 34 ml/min, P=0.01). CSFR to CPT was 1.31 +/- 0.20. Test-retest variability of CS volume flow was 5% at baseline and 6% during peak stress. CONCLUSION: Spiral CS VEC MRI at 3 T is a feasible and reproducible technique for measuring CS flow in asymptomatic women at risk for cardiovascular disease. Significant changes in CSFR to CPT are detectable, without demanding pharmacologic stress. PMID- 20302402 TI - The "mini tarsal strip" lateral canthopexy for lower eyelid laser-assisted blepharoplasty-indications, technique and complications in 614 cases. AB - The aim of this article is to describe the "mini tarsal strip procedure", a form of lateral canthal tendon plication to tighten the lower lid and give a better apposition of the lower eyelid to the globe. We describe this procedure in the context of transconjunctival lower lid blepharoplasty. PMID- 20302401 TI - The use of pericranial flaps for reconstruction and elevation of the lower eyelid. AB - PURPOSE: We present the novel approach of using pericranial flaps to reconstruct posterior lamellar eyelid defects or to achieve lower eyelid elevation. This technique has been employed in patients where standard tarso-conjunctival flaps are not an option and free posterior lamellar grafts cannot be supported due to the lack of viable anterior lamellar flaps. METHODS: Pericranial flap, comprising inferiorly based forehead periosteum and the overlying loose areolar tissue, is constructed using a vertical paramedian forehead incision. Flaps are tunnelled subcutaneously to emerge at the proximal aspect of the eyelid defect and extend to the lateral orbital rim. They are secured with absorbable sutures. An overlying full-thickness free skin-graft or flap is used for the anterior lamella. RESULTS: Eight patients underwent reconstruction or lower lid elevation. All patients achieved the predicted lower eyelid height with good cosmesis. Median follow-up 7.5 months (6-24 months). Indications were lower lid scarring/retraction (4), facial palsy (1), post BCC reconstruction (2), and exposed keratoprosthesis (1). In 2 (of 5) patients who had free skin-grafting, the overlying free skin-graft did not survive but acted as a biological dressing. All such patients still had good outcomes after epithelialisation of the flap. The posterior aspect of the pericranial flaps seems to act as an ideal substrate for conjunctivalisation, with little detrimental effect on the cornea. The robustness of the flap prevents the development of lid laxity over time. CONCLUSION: The pericranial flap is a versatile and robust flap that yields good cosmetic and functional outcomes when used in the reconstruction of posterior lamellar eyelid deficits. It is likely that, even when not viable, overlying free skin-grafts act as an excellent biological dressing until epithelialisation occurs. PMID- 20302404 TI - Age-based comparison of successful probing in Nepalese children with nasolacrimal duct obstruction. AB - PURPOSE: To compare the success rates of probing in Nepalese children younger than 2 years versus children older than 2 years with nasolacrimal duct obstruction (NLDO), and to identify factors associated with successful probing. MATERIALS AND METHODS: Data was collected and analyzed retrospectively on children who underwent probing under general anesthesia for NLDO at Tilganga Eye Centre, Nepal, from May 2004 to October 2008. We compared successful probing rates in children less than or equal to 2 years old (group 1) versus children greater than 2 years old (group 2), and analyzed whether various clinical factors were associated with successful probing. Successful probing was defined as complete resolution of all clinical signs (discharge, epiphora or increased tear lake) at the outcome visit one month following surgery. RESULTS: Data on 84 children (109 eyes) was reviewed. The mean age of children in group 1 and group 2 was 15.3 months and 37.3 months, respectively. The success rate of probing for the overall sample was 82.6% (90/109 eyes). The success rate in group 1 was 90.2% (55/61 eyes), and 72.9% (35/48 eyes) in group 2 (p=0.018). Increased age at time of probing (p=0.031) and duration of symptoms (p=0.027) were associated with decreased probing success. CONCLUSION: Early treatment of NLDO with probing, ideally prior to 2 years, is associated with better outcomes. Age appropriate intervention may reduce the incidence of complications from NLDO, which is highly prevalent in the low-lying areas of Nepal, including Kathmandu. PMID- 20302403 TI - Pathogenesis of primary acquired nasolacrimal duct obstruction. AB - PURPOSE: To assess the factors assumed to be contributed in pathogenesis of primary acquired nasolacrimal duct obstruction (PANDO). METHODS: In a prospective, controlled, interventional case series, 87 patients with symptomatic PANDO (case), 7 with traumatic nasolacrimal duct obstruction (NLDO) (control), 2 with congenital NLDO (control), and 70 asymptomatic females (control) were enrolled. Frequency of putting eye make-up (PANDO versus normal females), level of sexual hormones consisting of follicular stimulating hormone (FSH), luteal hormone (LH), estradiol, progesterone and testosterone (standard laboratory level), lacrimal sac biopsy for inflammation and fibrosis and immunohistochemistry for herpes simplex virus (HSV) type 1 and 2, and human papilloma virus were recorded. RESULTS: Severity of inflammation and fibrosis were not significantly different between case and control groups (P = 0.69), and between smokers and nonsmokers with PANDO (P = 0.15). Patients with severe preoperative symptoms showed significantly more lacrimal sac fibrosis (P = 0.018). No lacrimal sac pathology was found. Frequency of putting eye make-up was not significantly different between case and control group (0.596). Immunohistochemistry was negative for the viruses in all cases. There was no abnormal sexual hormone level in any case in this series. CONCLUSION: This study did not find any evidence in favor of the role of viral infection (HSV1, HSV2, HPV), eye make-up, and sex hormones in pathogenesis of PANDO. No abnormal pathology was found in lacrimal sac biopsy of patients with PANDO. PMID- 20302405 TI - Myocutaneous pedicle flap combined with a free skin graft for upper eyelid reconstruction. AB - PURPOSE: Repair of large upper eyelid defects can be accomplished by both 1-stage and 2-stage techniques some of which are complicated and time consuming. I here present a simple 1-stage technique for upper eyelid reconstruction. METHODS: The records and the peroperative and postoperative photographs of two patients who underwent reconstruction of large full-thickness upper eyelid defects after tumor removal were reviewed. The posterior lamella was reconstructed with lip mucosa in one patient and with a hard palate graft in the other. The anterior lamella was reconstructed with a myocutaneous pedicle flap from the remaining upper eyelid with its base medially or laterally. The resulting skin defect under the eyebrow was covered by a free skin graft from the contra lateral upper eyelid. RESULTS: In both patients the flap healed without necrosis or any other complications. In the case where the posterior lamella was reconstructed with lip mucosa the cosmetic appearance was excellent, and the cornea remained unaffected throughout the postoperative period. In the case where a hard palate graft was used the cosmetic appearance was good, but the corneal epithelium developed an edema and a soft contact lens was needed. The visual acuity was 20/20 and 20/40, respectively, 3 months postoperatively. CONCLUSION: Large upper eyelid defects can successfully be reconstructed by a pedicle flap from the infra brow area, which subsequently is covered by a free skin graft. PMID- 20302406 TI - Outcomes of 9 mm balloon-assisted endoscopic dacryocystorhinostomy: retrospective review of 97 cases. AB - OBJECTIVE: To retrospectively analyze the success rate of endoscopic dacryocystorhinostomy procedures performed by a single surgeon utilizing a novel 9mm endonasal balloon. METHODS: A retrospective clinical study was performed on 78 adult patients, 97 cases in total. All patients presented with nasolacrimal duct obstruction and underwent an endoscopic dacryocycstorhinostomy utilizing a 9 mm endonasal ballon. All patients completed follow-up from February 2003 to February 2009. Surgical success was defined as relief of epiphora and a patent surgical ostium demonstrated by free irrigation of saline through the nasolacrimal system 1 month after tube removal. RESULTS: Surgical success was achieved in 89 of the 97 cases (92%) following the primary surgery. Only 3 cases had revision surgery following the primary procedure. One of the 3 was successful. CONCLUSION: Endoscopic dacryocystorhinostomy utilizing a 9mm endonasal balloon has several advantages: it requires minimal instrumentation, does not require power drills or burrs, is quick with minimal bleeding, has a low complication rate, and a high success rate. Endoscopic balloon dacryocystorhinostomy offers a simpler endoscopic approach for the treatment of nasolacrimal duct obstruction, and is easily mastered by the Ophthalmic surgeon. PMID- 20302408 TI - Review of orbital exenteration from an eye care centre in Western India. AB - PURPOSE: Indications for orbital exenteration performed over a 10-year period from a tertiary eye care center in Western India. METHOD: Retrospective review of medical records of all patients who underwent exenteration of orbit over a period from January 1999 to April 2009, at a tertiary eye care center in western India. RESULT: Out of total 236 major orbital surgeries performed, 15 (6%) underwent orbital exenteration. Age ranged from 19 years to 75 years. Of these 9 were male and 6 female. Except for one case all exenteration were for malignant neoplasm. Lesions originated from eyelid in 8 (54%) cases, orbit in 5 (33%) cases and bulbar conjunctiva in 2 (13%) cases. Histopathological classification of the neoplasm were sebaceous carcinoma (4 cases), basal cell carcinoma (3 cases), squamous cell carcinoma (3 cases), adenoid cystic carcinoma (1 case), transitional cell carcinoma (1 case), malignant fibrous histiocytoma (1 case), lymphoma (1 case) and mucormycosis (1 case). CONCLUSION: Majority of exenterations performed were for neglected ocular or adnexal malignant lesions that could have been avoided provided patients reported earlier for treatment. Exenterations can be reduced by aggressive patient education about eye malignancy. PMID- 20302407 TI - Levator plication versus resection in congenital ptosis - a prospective comparative study. AB - PURPOSE: To compare levator plication with resection in congenital ptosis. METHODS: Prospective comparative randomized trial involving 20 eyes of 20 patients with age > 4 yrs, simple mild-to-moderate congenital ptosis with good-to fair amount of levator action were included. Patients were randomized to either levator resection or plication. Outcome was compared in terms of eyelid height and course of postoperative events. Data was compared using the paired and unpaired t-test. RESULTS: The mean M.R.D. 1 at the end of 3 months in Group A was 2.8 +/- 1.23 mm and in Group B was 1.12 +/- 0.83 mm (p value = 0.001). Plication did not improve levator action much. Resection lead to more alterations in Bell's, lid lag, lagophthalmos and persisting edema (3 cases). CONCLUSION: In 70% cases of congenital ptosis, good cosmetic outcome can be achieved with levator resection. With levator plication there are greater chances of drooping from fourth week onwards. The technique of plication, though simpler in approach failed to correct dystrophic muscle in congenital ptosis. PMID- 20302409 TI - Penetrating ocular trauma from trampoline spring. AB - The case is presented of a 12-year old boy who sustained severe penetrating ocular trauma while playing on a domestic trampoline. A main spring broke under tension and the hook had struck the eye at high velocity and penetrated the sclera. Primary repair was undertaken but on review it became apparent the eye could not be salvaged. Evisceration was carried out and an orbital implant was placed. Post-operative cosmesis is acceptable. This type of injury has not been reported before. Adult supervision of children on trampolines is recommended to minimise the chance of serious injury. PMID- 20302410 TI - Orbital apex syndrome from blunt ocular trauma. AB - Orbital apex syndrome (OAS) is a rare condition due to a range of pathological processes around the optic nerve foramen and the superior orbital fissure causing characteristic functional loss. It is a rare complication of trauma and results from penetrating injuries as well as those involving bony fractures. We present a case of OAS from non-penetrating ocular trauma without bony involvement. PMID- 20302411 TI - Orbital cavitary rhabdomyosarcoma: a diagnostic dilemma. AB - The authors present a rare form of orbital cavitary rhabdomyosarcoma in which lymphangioma was mistakenly diagnosed on the basis of echography and MRI. Rhabdomyosarcoma can usually be differentiated from lymphangioma by echographic and MR imaging, because cavitation is very rare in orbital rhabdomyosarcoma, but rhabdomyosarcoma should be suspected whenever the clinical presentation of a rapidly progressive unilateral exophthalmos is observed in a child. PMID- 20302412 TI - The challenge of orbital decompression in a patient with multiple autoimmune diseases and graves' orbitopathy: a case report and review of literature. AB - The association between multiple autoimmune diseases can make management of the ocular proptosis very difficult and challenging for the orbit surgeon. We report an interesting case of a patient affected by Stiff person syndrome, type-1 diabetes and Graves' disease with Graves' orbitopathy, who underwent orbital decompression. Anaesthesiologic problems, as well as factors affecting the post operative result, are discussed in detail; pertinent literature review was performed and discussed. PMID- 20302413 TI - Two different presentations of orbital echinococcosis: a report of two cases and review of the literature. AB - PURPOSE: To report two patients with different presentations of orbital echinococcosis, namely hydatid and alveolar cysts and to compare their clinical, imaging and histopathologic findings and treatment. METHODS: This retrospective study includes two young rural children who were referred because of progressive proptosis. RESULTS: Orbital imaging in both cases revealed cystic intraorbital lesions. With a clinical suspicion of hydatid and alveolar cysts, both patients underwent intact surgical excision. Histopathologic evaluation confirmed the diagnoses. CONCLUSIONS: Clinical findings and imaging can help in the preoperative diagnosis of patients with orbital echinococcosis. Knowledge of the nature of cystic orbital lesions is important in preventing complications. Alveolar cysts are more invasive than hydatid cysts and their treatment is more complicated. PMID- 20302414 TI - Mid line craniofacial defects and morning glory disc anomaly with clinical anophthalmos-a distinct clinical entity. AB - Morning glory syndrome (MGS) is a congenital optic disc dysplasia often associated with craniofacial anomalies, especially basal encephalocele. We report a case of a 4-month-old male baby, who was referred to our institute with the complaints of decreased vision. This is the first report from Northeastern part of India as per our knowledge. PMID- 20302415 TI - Optic nerve compression by an intraorbital megadolichoectatic ophtalmic artery. AB - A 47-year-old woman, physically active, presented with a history of progressive isolated right eye visual loss (20/200). Ophtalmological examination with Goldmann's perimetry showed a Marcus Gunn pupil, an optic disc temporal pallor and a central scotoma on the affected eye. CT scan and cerebral angiography demonstrated an abnormally wide and elongated (megadolichoectatic) intraorbital ophthalmic artery responsible for optic nerve compression in the optic canal. Pulse steroid therapy was chosen and allowed recuperation of right eye visual acuity to 20/20. A 3-months' follow-up was decided and to date, 1 year later, she fell back to 20/40 with a normal right eye visual field. The authors compare these clinical and radiological findings with intraorbital aneurysms and discuss the therapeutic options for this extremely rare form of vascular disease. PMID- 20302416 TI - Bilateral necrotising fasciitis of the ocular adnexa secondary to Pseudomonas aeruginosa septicaemia in a HIV-positive child. PMID- 20302417 TI - Real-time elderly activity monitoring system based on a tri-axial accelerometer. AB - PURPOSE: The purpose of this study is to develop an automatic human movement classification system for the elderly using single waist-mounted tri-axial accelerometer. METHODS: Real-time movement classification algorithm was developed using a hierarchical binary tree, which can classify activities of daily living into four general states: (1) resting state such as sitting, lying, and standing; (2) locomotion state such as walking and running; (3) emergency state such as fall and (4) transition state such as sit to stand, stand to sit, stand to lie, lie to stand, sit to lie, and lie to sit. To evaluate the proposed algorithm, experiments were performed on five healthy young subjects with several activities, such as falls, walking, running, etc. RESULTS: The results of experiment showed that successful detection rate of the system for all activities were about 96%. To evaluate long-term monitoring, 3 h experiment in home environment was performed on one healthy subject and 98% of the movement was successfully classified. CONCLUSIONS: The results of experiment showed a possible use of this system which can monitor and classify the activities of daily living. For further improvement of the system, it is necessary to include more detailed classification algorithm to distinguish several daily activities. PMID- 20302418 TI - Perceptions of health care workers prescribing augmentative and alternative communication devices to children. AB - PURPOSE: Access to assistive devices is critical for most children with disabilities to function in society. Despite this, there remain high levels of unmet needs and an underutilisation of augmentative and alternative communication (AAC) devices. Yet, relatively little is known about the challenges that clinicians encounter in prescribing AAC devices. METHOD: In-depth qualitative semi-structured interviews were conducted with 11 speech language pathologists and occupational therapists who are current authorisers for AAC devices. RESULTS: The findings suggest that there are several barriers (technical, social and political) influencing clinicians' decision to prescribe AAC devices. Technical challenges include the complexity of devices and viewing technology as a cure. Social barriers involve socio-demographic differences, readiness to use a device, social acceptance, attitudes, family's view of technology, and the priority of communication. Finally, several political barriers such as a shortage of speech pathologists, a complex prescription review process, inconsistent follow-up procedures, limitations of the consultative model, and gaps in funding and policy influenced clinicians' ability to prescribe AAC devices. Differences in philosophy of technology also influenced health providers' decision to prescribe AAC devices. CONCLUSIONS: Service providers and policy makers should be cognizant of the contextual factors influencing health provider's decision to prescribe AAC devices. PMID- 20302419 TI - An affordable, computerised, table-based exercise system for stroke survivors. AB - PURPOSE: Loss of hand function as a result of upper limb paresis after a stroke leads to reduced independence. Robotic-assisted therapy with virtual reality leads to improvements in motor function, but there is a need to improve the cost benefit ratio of these therapies. This case series study investigated augmented reality computer games which provided a rewarded, goal-directed task to upper limb rehabilitation via a gravity supported reaching task. METHODS: A computer game was developed to motivate chronic stroke survivors to undertake gravity supported reaching tasks performed on a table, and a focus group study investigated the application of this device for rehabilitation. From the focus group, a simple device was developed to improve the quality of the exercise and a further focus group study investigated a variety of computer games to determine motivations for undertaking rehabilitation exercises. RESULTS: Of the four participants in the case study, two showed improvement in ability to play the game and in arm function. Participants enjoyed playing a range of computer games and felt that the system provided a worthwhile exercise. Motivation for undertaking exercise with the system included: intellectual stimulation during game play, feedback such as game score, gaining physical benefits from the exercise, the system tolerating varying levels of disability, ability to relate to the game and ability to use the system in social groups. CONCLUSIONS: A low cost device has been developed which increases the exercise of gravity supported reaching movements, provides goal-directed tasks with rewards and motivates the user to undertake extended rehabilitation. PMID- 20302420 TI - Leveraging retained physical capabilities to improve quality of life as assessed by persons with severe motor impairments. AB - PURPOSE: The main objective of this article is to present an alternative method of interacting with a computer which empowers persons with very severe motor impairments to leverage retained capabilities in order to independently control parts of their daily lives. The input strategy is based on tiny intentional contractions of a single muscle of choice (requiring a minimum of physical contribution only) which are used as selection markers in the context of scanning. METHOD: To demonstrate the usefulness of the idea, two applications (combined in a single software system) have been implemented (initially): a module turning the PC into a Universal Remote Control and a Text-To-Speech module. The system has finally been supplemented by a third application offering to effortlessly make telephone calls. RESULTS: A simple experiment requesting the speed of the scanning scheme shows that the theoretical concept really works. Furthermore, the usability by novice users from the target population is proven in a user study focusing on the telephony application. CONCLUSIONS: It is concluded that the approach has a large potential for persons with severe physical disabilities, meaning that the resulting system is indeed able to improve its users' quality of life. PMID- 20302421 TI - Cannibals in space: the coevolution of cannibalism and dispersal in spatially structured populations. AB - The propensity for cannibalism varies considerably both within and between species. Currently we have little understanding of both the causes of this variation and its evolutionary consequences for other life-history traits. We examine how different levels of spatial structure affect the evolution of cannibalism and how cannibalism in turn drives the evolution of dispersal. Using pair approximations and simulations, we show that cannibalism can easily evolve in spatially structured populations as long as some dispersal exists. Furthermore, for a wide range of intermediate levels of spatial structure, we find the possibility of evolutionary branching leading to polymorphism in cannibalism. We also show that cannibalism itself can have important evolutionary consequences and select for increased dispersal rates, thus helping to determine the spatial structure of populations. The coevolution of cannibalism and dispersal results in the evolution of various alternative life-history strategies with different dispersal and cannibalism regimes. Which strategy evolves depends on the environmental conditions that determine initial cannibalism rates. Our results therefore suggest that differences in spatial structure could explain variation in the propensity for cannibalism and cannibalistic polyphenism. Furthermore, results emphasize that cannibalism can drive the evolution of other life-history traits and determine the spatial structure of natural populations. PMID- 20302423 TI - Temporal variation in the carrying capacity of a perennial grass population. AB - Density dependence and, therefore, K (carrying capacity, equilibrium population size) are central to understanding and predicting changes in population size (N). Although resource levels certainly fluctuate, K has almost always been treated as constant in both theoretical and empirical studies. We quantified temporal variation in K by fitting extensions of standard population dynamic models to 16 annual censuses of a population of the perennial bunchgrass Bouteloua rigidiseta. Variable-K models provided substantially better fits to the data than did models that varied the potential rate of population increase. The distribution of estimated values of K was skewed, with a long right tail (i.e., a few "jackpot" years). The population did not track K closely. Relatively slow responses to changes in K combined with large, rapid changes in K sometimes caused N to be far from K. In 13%-20% of annual intervals, K was so much larger than N that the population's dynamics were best described by geometric growth and the population was, in effect, unregulated. Explicitly incorporating temporal variation in K substantially improved the realism of models with little increase in model complexity and provided novel information about this population's dynamics. Similar methods would be applicable to many other data sets. PMID- 20302422 TI - Animals that randomly reorient at cues left by correlated random walkers do the Levy walk. AB - For many years, correlated random walks have been the dominant conceptual models used in describing nonoriented animal movements. Here it is shown that Levy walk movement patterns will arise from animals that randomly reorient on detection of odor trails and/or scent marks left by correlated random walkers. The emergent Levy walk movement patterns are advantageous when one is randomly searching for sparsely distributed resources. Consequently, there will be strong selection pressures for the aforementioned reorientation process when resources are sparsely distributed within unpredictable environments inhabited by correlated random walkers. This selection pressure may drive the evolution of Levy walk strategies in these landscapes. The mechanism may account for the Levy walk movement patterns of microzooplankton in the presence of mobile phytoplankton and those of a species of African jackal that scavenges within landscapes inhabited by other animal species. These findings show that Levy walks and fractal scaling do not exist outside of the correlated random-walk paradigm, as is widely thought, but are instead natural consequences of it. PMID- 20302424 TI - The condition dependence and heritability of signaling and nonsignaling color traits in paper wasps. AB - Research on quality signal development typically focuses on signals with production costs; less is known about signals that lack production costs (conventional signals). Here, I test the condition dependence and heritability of the facial patterns that function as a conventional signal of quality in Polistes dominulus wasps. Two aspects of facial patterns are compared: (1) amount of black pigment (no signal value) and (2) disruption in the black pigment's distribution (quality signal). When colonies received the same diet, they produced offspring with similar facial patterns and both traits were heritable. However, experimental diet manipulation substantially influenced quality signal development. Wasps fed unlimited caterpillars developed more disrupted facial patterns than wasps fed a restricted diet. Further, signal heritability was obscured following the diet treatment. In contrast, the nonsignaling trait was not influenced by the diet treatment and remained heritable. Overall, the quality signal in P. dominulus is condition dependent and heritable, but its heritability may be obscured by environmental variance. The nonsignaling aspect of wasp facial patterns is not condition dependent and is more consistently heritable across environments. Therefore, the information a signal conveys may be influenced by its developmental properties rather than its honesty-ensuring cost or the pigments that constitute it. PMID- 20302425 TI - When and why do territorial coalitions occur? Experimental evidence from a fiddler crab. AB - Neighboring territory owners are often less aggressive toward each other than to strangers ("dear enemy" effect). There is, however, little evidence for territorial defense coalitions whereby a neighbor will temporarily leave his/her own territory, enter that of a neighbor, and cooperate in repelling a conspecific intruder. This is surprising, as theoreticians have long posited the existence of such coalitions and the circumstances under which they should evolve. Here we document territorial defense coalitions in the African fiddler crab Uca annulipes, which lives in large colonies wherein each male defends a burrow and its surrounding area against neighbors and "floaters" (burrowless males). Fights between a resident and a floater sometimes involve another male who has left his territory to fight the floater challenging his neighbor. Using simple experiments, we provide the first evidence of the rules determining when territorial coalitions form. Our results support recent models that suggest that these coalitions arise from by-product mutualism. PMID- 20302426 TI - Differential response to circularly polarized light by the jewel scarab beetle Chrysina gloriosa. AB - Circularly polarized light is rare in the terrestrial environment, and cuticular reflections from scarab beetles are one of the few natural sources. Chrysina gloriosa LeConte 1854, a scarab beetle found in montane juniper forests of the extreme southwestern United States and northern Mexico, are camouflaged in juniper foliage; however, when viewed with right circularly polarizing filters, the beetles exhibit a stark black contrast. Given the polarization-specific changes in the appearance of C. gloriosa, we hypothesized that C. gloriosa can detect circularly polarized light. We tested for phototactic response and differential flight orientation of C. gloriosa toward different light stimuli. Chrysina gloriosa exhibited (a) positive phototaxis, (b) differential flight orientation between linear and circularly polarized light stimuli of equal intensities, and (c) discrimination between circularly polarized and unpolarized lights of different intensities consistent with a model of circular polarization sensitivity based on a quarter-wave plate. These results demonstrate that C. gloriosa beetles respond differentially to circularly polarized light. In contrast, Chrysina woodi Horn 1885, a close relative with reduced circularly polarized reflection, exhibited no phototactic discrimination between linear and circularly polarized light. Circularly polarized sensitivity may allow C. gloriosa to perceive and communicate with conspecifics that remain cryptic to predators, reducing indirect costs of communication. PMID- 20302427 TI - The effects of temporal resolution on species turnover and on testing metacommunity models. AB - Patterns of low temporal turnover in species composition found within paleoecological time series contrast with the high turnover predicted by neutral metacommunity models and thus have been used to support nonneutral models. However, these predictions assume temporal resolution on the scale of a season or year, whereas individual fossil assemblages are typically time averaged to decadal or centennial timescales. We simulate the effects of time averaging by building time-averaged assemblages from local dispersal-limited, nonaveraged assemblages and compare the predicted turnover with observed patterns in mollusk and ostracod fossil records. Time averaging substantially reduces temporal turnover such that neutral predictions converge with those of trade-off and density-dependent models, and it tends to decrease species dominance and increase the proportion of rare species. Observed turnover rates are comparable to an appropriately scaled neutral model: patterns of high community stability can be produced or reinforced by time averaging alone. The community attributes of local time-averaged assemblages approach those of the metacommunity. Time-averaged assemblages are thus unlikely to capture attributes arising from processes operating at small spatial scales, but they should do well at capturing the turnover and diversity of metacommunities and thus will be a valuable basis for analyzing the large-scale processes that determine metacommunity evolution. PMID- 20302428 TI - Economic burden of ventilator-associated pneumonia based on total resource utilization. AB - OBJECTIVES: To characterize the current economic burden of ventilator-associated pneumonia (VAP) and to determine which services increase the cost of VAP in North American hospitals. DESIGN AND SETTING: We performed a retrospective, matched cohort analysis of mechanically ventilated patients enrolled in the North American Silver-Coated Endotracheal Tube (NASCENT) study, a prospective, randomized study conducted from 2002 to 2006 in 54 medical centers, including 45 teaching institutions (83.3%). METHODS: Case patients with microbiologically confirmed VAP (n = 30)were identified from 542 study participants with claims data and were matched by use of a primary diagnostic code, and subsequently by the Acute Physiology and Chronic Health Evaluation II score, to control patients without VAP (n = 90). Costs were estimated by applying hospital-specific cost-to charge ratios based on all-payer inpatient costs associated with VAP diagnosis related groups. RESULTS: Median total charges per patient were $198,200 for case patients and $96,540 for matched control patients (P < .001); corresponding median hospital costs were $76,730 for case patients and $41,250 for control patients (P = .001). After adjusting for diagnosis-related group payments, median losses to hospitals were $32,140 for case patients and $19,360 for control patients (P = .151). The median duration of intubation was longer for case patients than for control patients (10.1 days vs 4.7 days; P < .001), as were the median duration of intensive care unit stay (18.5 days vs 8.0 days; P < .001) and the median duration of hospitalization (26.5 days vs 14.0 days; P < .001). Examples of services likely to be directly related to VAP and having higher median costs for case patients were hospital care (P < .05) and respiratory therapy (P < .05). CONCLUSIONS: VAP was associated with increased hospital costs, longer duration of hospital stay, and a higher number of hospital services being affected, which underscores the need for bundled measures to prevent VAP. TRIAL REGISTRATION: NASCENT study ClinicalTrials.gov Identifier: NCT00148642. PMID- 20302429 TI - Cataract surgery rates in latin america: a four-year longitudinal study of 19 countries. AB - PURPOSE: To collect cataract surgery rates data in 19 Latin American countries over a 4-year period as data published to date have been limited. METHODS: Cataract surgery rates were obtained from National Society of Ophthalmology, National VISION 2020/Prevention of Blindness Committee and Ministry of Health representatives for each country for 2005 to 2008. Economic (gross national income per capita) and other data were collected from publicly available databases. Linear and power correlations between gross national incomes and cataract surgery rates were calculated. RESULTS: Over the study period, most countries increased their cataract surgery rates, with the largest increases observed for Venezuela (186%), Nicaragua (183%), Costa Rica (100%), Uruguay (97%), and Peru (88%). Mean cataract surgery rates for 2005, 2006, 2007, and 2008 for the ensemble of countries were 1545, 1684, 1660, and 1822 per million population, respectively, with a growth over the study period of 17.9%, concurrent with an increase of 57 million (11.5%) in the population. A good correlation between cataract surgery rate and gross national income per capita was found (P < .001). CONCLUSIONS: Although progress is being made in the region, the cataract surgery rates represent only one parameter. When they are examined in the context of cataract surgical coverage it is clear that substantial proportions of bilaterally blind persons are still not receiving surgery. PMID- 20302430 TI - The prevalence of blindness and cataract surgery in rautahat district, Nepal. AB - PURPOSE: The Gaur Eye Hospital, which provides eye care services to the people in Rautahat and adjacent districts, completed 9 years of operation in 2006. Over 14,000 cataract surgeries were performed during this period. This study aimed to ascertain the impact of the hospital services by estimating the prevalence of blindness, visual impairment and cataract surgical coverage among the older adult population of the Rautahat district. METHODS: People aged 50 years and older were enrolled in this study that used a stratified cluster design. Subjects in 32 randomly selected clusters were identified through door-to-door visits, presenting and corrected visual acuities measurement, and clinical examination by ophthalmologists were conducted at a centrally located site. RESULTS: Of the 5,533 identified subjects, 85.3% were examined. Blindness was defined as presenting with visual acuity < 6/60 in both eyes. Blindness was found in 17.4% (95% Confidence Interval: 15.1 to 19.7); however, 55.6% of individuals examined had vision < 6/18 in one or both eyes. Cataracts were the principal cause of blindness in 82.1%, and were associated with elder age, illiteracy and female gender. Surgical coverage was found to be 37.3%. CONCLUSION: The findings suggest that despite 9 years of hospital and community eye care services the prevalence of blindness in this area is still challengingly high and the cataract surgical coverage unacceptably low. Community outreach awareness programs and accessibility for the Nepali cataract blind to the hospital need to be upgraded. PMID- 20302431 TI - Prevalence and causes of severe visual impairment and blindness among children in the lorestan province of iran, using the key informant method. AB - PURPOSE: To estimate the prevalence and causes of severe visual impairment and blindness among children in Lorestan province of Iran, and to assess the feasibility of the Key Informant Method in this setting. METHODS: Potential cases were identified using the Key Informant Method, in 3 counties of Lorestan province during June through August 2008, and referred for examination. Causes of severe visual impairment/blindness were determined and categorized using standard World Health Organization methods. RESULTS: Of 123 children referred for examination, 27 children were confirmed to have severe visual impairment/blindness or blindness. The median age was11 years (interquartile range 6-13), and 59% were girls. After adjusting for non-attenders, the estimated prevalence of severe visual impairment/blindness was 0.04% (0.03-0.05). The main site of abnormality was retina (44%), followed by disorders of the whole eye (33%). The majority of causes had a hereditary etiology (70%), which was associated with a family history of blindness (P = 0.002). Potentially avoidable causes of severe visual impairment/blindness were found in 14 children (52%). Almost all children with severe visual impairment/blindness had a history of parental consanguinity (93%). CONCLUSIONS: Our findings suggest a moderate prevalence of childhood blindness in the Lorestan province of Iran, a high proportion of which may be avoidable, given improved access to ophthalmic and genetic counselling services in rural areas. The Key Informant Method is feasible in Iran; future research is discussed. PMID- 20302432 TI - Travel and implications for the elimination of trachoma in ethiopia. AB - PURPOSE: Trachoma is the leading infectious cause of blindness. The World Health Organization has set a goal of reducing the trachoma disease burden to a level where it is no longer a public health concern by the year 2020. Some investigators feel that local elimination of ocular chlamydia infection is possible, but little has been done to study the likelihood of reintroduction of infection from neighboring areas. Mass administration of azithromycin has been shown to dramatically reduce the prevalence of infection in many villages in central Ethiopia. However, after treatment is discontinued, infection returns. Reintroduction of infection could occur from the few remaining infected cases in a treated community or from outside the community. People traveling between villages might be responsible thus complicating the elimination of trachoma. METHODS: We conducted a survey to assess the travel pattern of the Gurage zone residents in Ethiopia. Seven hundred and seventeen households with at least one child aged 1-5 years in 48 villages were surveyed to collect the details of travel in 1 month prior to the survey. RESULTS: Seventy-eight percent of the surveyed households had at least one traveler, with the majority being women. Pre school children, the main reservoir of clinically active infection, rarely traveled. Most travel was to the market or to school, and most for less than 1 day. CONCLUSIONS: Travel routinely takes place in these villages. Trachoma control programs in this area might consider treating areas with the same markets and schools in the same period to increase the efficacy of mass treatment. PMID- 20302433 TI - Prevalence of pseudoexfoliation syndrome among adult Spanish in the Salnes eye Study. AB - PURPOSE: To estimate the prevalence of Pseudoexfoliation syndrome (PXF) and to investigate its relationship with systemic and ocular diseases and lifestyle factors in a general adult population in north-western Spain. METHODS: An age stratified random sample of 1155 subjects was drawn from the population aged 40 years and over of O Salnes (Spain). From 937 eligible subjects, 619 (66.1%) participated (mean age (Standard Deviation [SD]): 63.4 (14.5) years, range: 40 96, 37.0% males). An interview to collect past history of ocular and systemic diseases and lifestyle details, and a comprehensive ophthalmic evaluation were performed. Study subjects with typical pseudoexfoliative material on the anterior capsule or in the pupil margin were labelled as having PXF. A design based analysis was performed and all calculations were weighted to give unbiased estimates. RESULTS: The prevalence of PXF was 6.5% (95% confidence interval [CI]:4.9-8.1). PXF rates increased significantly with age (P = 0.000). No cases of PXF were detected in subjects between 40 and 60 years. Prevalence of PXF was 8.0% (95% C I5.4-11.6) in men and 5.4% (95% CI 3.8-7.6) in women (P = ns). The prevalence of glaucoma in subjects with PXF was 19.6% (95% CI 8.2-40.0). After controlling for age and sex, glaucoma, cataract surgery, rose bengal staining and diabetes were associated with PXF but only glaucoma and rose bengal staining associations remained significant in a multivariate model. CONCLUSIONS: PXF is common among older individuals in north-western Spain. Subjects with pseudoexfoliation have a significantly higher prevalence of glaucoma than subjects without. An abnormal ocular surface detected by rose bengal staining is highly prevalent among subjects with pseudoexfoliation. PMID- 20302434 TI - Geographical distribution of ophthalmologists before and after the new postgraduate training program in Japan. AB - PURPOSE: To assess the geographical distribution of ophthalmologists in Japan before and after the start of a new postgraduate training program, which was suggested to exacerbate the uneven distribution of physicians. METHODS: The number of physician per million population was calculated for ophthalmologists by using adjusted municipal boundaries and the data from physician censuses performed in 1996 and 2006, as well as the population censuses performed in 1995 and 2005, respectively. The Gini coefficients, income inequality measure that ranges from 0 (perfect equality) to 1 (perfect inequality), and 95% confidence intervals (95%CIs) were computed from the Lorenz curves for the 2 periods. RESULTS: The total number of ophthalmologists increased from 10,982 to 12,362 over the last decade. The Gini coefficient (95%CI) for ophthalmologists was 0.405 (0.314-0.496) and 0.353 (0.272-0.434) in 1996 and 2006, respectively. CONCLUSIONS: The geographical distribution of ophthalmologists in 2006 was better than that in 1996, although there was no statistically significant change. There is no evidence that the new postgraduate training program encouraged an imbalance in the geographical distribution of ophthalmologists. PMID- 20302435 TI - Selecting healthcare information systems provided by third-party vendors: a mind map beyond the manuals. AB - The selection of a new healthcare information system (HIS) has always been a daunting process for clinicians, health care providers and policy makers. The objective of this study is to present the lessons learned and the main findings from several relevant case studies to support this process. Data were collected by retrospectively reviewing the summative results of three well-established systems, acquiring feedback from two E.U. projects, and conducting semi structured interviews with a number of collaborators involved in electronic healthcare interventions. Selection issues were identified and classified into the following five categories: (i) data creation, (ii) data management, (iii) data sharing, (iv) data presentation and (v) modules management. A mind map was also structured to provide a more manageable list of issues concerning the most common electronic clinical technologies (e-CT). The vendor manual is intended as an overview of the merchandise e-CT and therefore has limited potential in supporting effectively the selection process of a new HIS. The present classification and the mind map - based on lessons learned - provide a ready-to use toolkit for supporting the HIS selection process when healthcare organisations are unable to employ research development groups to lay the groundwork for building a new HIS from scratch. PMID- 20302436 TI - Measuring the impact of the computer on the consultation: an open source application to combine multiple observational outputs. AB - A diverse range of tools and techniques can be used to observe the clinical consultation and the use of information technology. These technologies range from transcripts; to video observation with one or more cameras; to voice and pattern recognition applications. Currently, these have to be observed separately and there is limited capacity to combine them. Consequently, when multiple methods are used to analyse the consultation a significant proportion of time is spent linking events in one log file (e.g. mouse movements and keyboard use when prescribing alerts appear) with what was happening in the consultation at that time. The objective of this study was to develop an application capable of combining and comparing activity log-files and with facilities to view simultaneously all data relating to any time point or activity. Interviews, observations and design prototypes were used to develop a specification. Class diagram of the application design was used to make further development decisions. The application development used object-orientated design principles. We used open source tools; Java as the programming language and JDeveloper as the development environment. The final output is log file aggregation (LFA) tool which forms part of the wider aggregation of log files for analysis (ALFA) open source toolkit ( www.biomedicalinformatics.info/alfa/ ). Testing was done using sample log files and reviewed the application's utility for analysis of the consultation activities. Separation of the presentation and functionality in the design stage enabled us to develop a modular and extensible application. The application is capable of converting and aggregating several log files of different formats and displays them in different presentation layouts. We used the Java Media Framework to aggregate video channels. Java extensible mark-up language (XML) package facilitated the conversion of aggregated output into XML format. Analysts can now move easily between observation tools and find all the data related to an activity. The LFA application makes new analysis tasks feasible and established tasks much more efficient. Researchers can now store multiple log file data as a single file isolate and investigate different doctor computer-patient interaction. PMID- 20302437 TI - Determinants of the frequency of online health information seeking: results of a web-based survey conducted in France in 2007. AB - In the general population, social disparities in Internet practices have been less described than disparities in health information access. Aim is to determine whether there are differences in the frequency of Internet use for health information among health seekers. We conducted an Internet-based survey from November 2006 to March 2007. We considered the 3720 residents of France who had searched for health information during the previous 12 months. This study reveals different uses of the Internet for health information seeking (HIS) between men and women and between the general population and people who work in the health sector. Health status, taking care of somebody who is sick, and active Internet use were associated with higher frequencies of online HIS to varying degrees. The effects of age and level of education were not clear or were not significant. Greater health concerns and some issues in the physician-patient relationship were associated with higher frequencies of Internet use for HIS in the general population. Considering that this increasing use of online tools for HIS is consistent with current public health policies that promote the development of the 'informed patient', one should remain cautious about these social disparities in online HIS practices. PMID- 20302438 TI - Use of the LIFE-H in stroke rehabilitation: a structured review of its psychometric properties. AB - PURPOSE: To perform a structured review of the psychometric properties specific to the stroke population of the Assessment of Life Habits (LIFE-H). This tool measures quality of social participation, an important but under-evaluated aspect of stroke recovery. METHOD: A structured review of publications at MEDLINE; Embase, CINAHL, and the Cochrane Library using the following terms: LIFE-H, life habits, psychometric properties, measurement properties, reliability, repeatability, validity, responsiveness, appropriateness, ceiling effects, and floor effects. RESULTS: Eleven studies were identified specific to stroke. Test retest reliability was excellent (Intraclass correlation coefficients [ICCs] ranging from 0.80 to 0.95). Inter-rater reliability ranged from adequate to excellent (r = 0.64-0.91) as well as agreement between responses of clients with stroke and their proxies (ICC ranging from 0.73 to 0.82). Convergent validity was adequate to excellent (r = 0.57-0.91) between the LIFE-H and two measures of functional independence. Two studies, one using patients and one using caregivers, suggest the LIFE-H is able to detect change over time. CONCLUSIONS: The LIFE-H is a psychometrically sound measure of quality of social participation for use in post-stroke assessment and is responsive to change. PMID- 20302439 TI - Lung transplant recipients' views on the integration of their new organs. AB - AIM: Although donorship issues and the integration of the new organs are the most distinguishing aspects of lung transplantation (LTx) compared to other kinds of 'high-tech' medicine, there is a paucity of papers on that matter. Therefore, we aimed to evaluate these aspects in young adult LTx recipients with at least 1 year survival. METHODS: Semi-structured interviews; content analysis of specific parts of the interviews; frequency distributions of resulting categories. SAMPLE: Forty-five adults aged 18-42 years (mean: 32 +/- 5.5 years). Post-transplant survival ranged from 1 to 11 years. RESULTS: The majority of recipients (60%) fulfilled criteria of denial towards the foreign organ and/or the donor. However, they were rather sensitive towards the ethical and psychological impact of the upcoming option of living donorship in LTx. Also, the majority of recipients (79%) understood that there might as well be good reason not to opt for a LTx. CONCLUSIONS: LTx recipients appeared at first sight 'pragmatic' towards the gift of life, but they remained sensitive to its ethical and psychological challenges. PMID- 20302440 TI - Pain prevalence and its impact on the quality of life in a sample of Turkish children with cerebral palsy. AB - PURPOSE: To investigate the measurement properties of the Pain Evaluation Scale (PES), to estimate the prevalence of pain based on the PES data, and to evaluate the impact of pain on the quality of life (QoL) in a sample of Turkish children with CP. METHOD: A total of 346 children with CP participated in a cross sectional study. The Gross Motor Function Classification System (GMFCS), PES, Wong-Baker FACES Pain Rating Scale, and the Child Health Questionnaire (CHQ-PF50) were used as the assessment tools. RESULTS: The Cronbach's alpha coefficient was 0.90 for the PES. The PES score was moderately correlated with the bodily pain subscale score, and very weekly with the mental health subscale score of the CHQ PF50. For the threshold value of 2 on the PES, sensitivity and specificity were 91.1% and 100%, respectively. Overall, apparent prevalence and true prevalence of pain were 69.1% and 75.9%, respectively. There was a significant negative effect of pain on the QoL of subjects. The pain also negatively affected parent's personal time and caused limitations in family activities. CONCLUSIONS: The PES is valid and reliable pain assessment tool for children with CP. Pain is a frequent health problem and has severe consequences both on the cerebral palsied children's QoL and their family. PMID- 20302441 TI - Experiences of psychosocial adjustment within 18 months of amputation: an interpretative phenomenological analysis. AB - PURPOSE: To explore participants' experiences of psychosocial adjustment within 18-months following amputation in a manner that can inform further research and clinical practice. METHOD: Transcript data from eight semi-structured interviews were analysed using Interpretative Phenomenological Analysis. RESULTS: Three super-ordinate themes emerged from the analysis: (1) pre-amputation decision making process and control, (2) renegotiation of self-identity and the struggle to accept a new 'disabled' identity, and (3) adjustment as a social process. CONCLUSION: This research furthers understanding of pre-acute, acute and post acute adjustment processes from the insider-perspective of individuals who have experienced amputation. A picture emerged in which individuals adjusted to amputation and its sequelae through a process of renegotiation of self-identity that was mediated through a wide range of decisional, informational and social factors. Suggestions for clinical practice and further research are discussed. PMID- 20302442 TI - Project Shake-It-Up: using health promotion, capacity building and a disability studies framework to increase self efficacy. AB - PURPOSE: Project Shake-It-Up provided a health promotion and capacity building program for individuals with spinal cord injury, multiple sclerosis, and related neurological impairments. Major research aims were to evaluate changes in participants' self-efficacy, ability to set/achieve goals, and perceived independent-living status. METHODS: Participants completed self-efficacy measures at baseline, program completion, 6- and 12-month follow-up, and set health and/or independent living goals. Progress toward goal attainment was monitored periodically and assessed qualitatively. RESULTS: There was a statistically significant difference in the change in self-efficacy scores for intervention participants compared to non-participants. Participants gained independent-living skills and confidence in their abilities to set and achieve a variety of goals, in the areas of education, employment, housing, transportation, accessing community resources and activities, participation in sports and leisure, and health promotion. CONCLUSIONS: Researchers evaluated results using a disability studies framework of empowerment which recognizes the role of environment, gender, race/ethnicity, and social status in the experience of disability. Participants reported increased independence, community access, and participation. They took action in multiple arenas with changes observed and reported in areas of intrapersonal, interpersonal, and behavioral functioning that indicated greater personal empowerment. PMID- 20302443 TI - Exploring older peoples' experiences of nocturia: a poorly recognised urinary condition that limits participation. AB - PURPOSE: This study sought to understand the experience of living and coping with nocturia, from the perspective of community-living older men and women. METHOD: Individual semi-structured interviews were undertaken with 32 older people with self-reported nocturia of twice nightly or more. RESULTS: Four key characteristics of nocturia were identified. Nocturia was described as simultaneously debilitating, frustrating, distressing and puzzling. It impacted on sleep patterns and quality, personal relationships and increased the fear of falling among older people when rising to use the toilet at night. Previously unrecognised variability and unpredictability in the condition were highlighted features. Nocturia was not prioritised for health intervention. There were gender differences in initial help-seeking however once prostate disease was eliminated, self-management strategies to cope with the effects of nocturia were the norm. CONCLUSIONS: . This study indicates that nocturia has a widespread and profound influence on older people's quality of life and participation, despite being regarded as a relatively benign condition by both older people and health professionals. Several features of the condition, which have the potential for great impact, are poorly recognised in particular its variability and unpredictability. PMID- 20302444 TI - Perceived spasticity in chronic spinal cord injured patients: associations with psychological factors. AB - PURPOSE: To explore the association between perceived spasticity and psychological factors (pain sensations, coping strategies, and illness cognitions) in chronic spinal cord injured (SCI) patients. METHODS: Cross sectional study using a set of questionnaires was designed for chronic complete patients with SCI and with self-reported leg spasticity. Outcome measures were Visual Analogue Scale for average perceived leg spasticity (VAS(Spasticity)), VAS(Pain) for average perceived pain sensations in the leg, Utrecht Coping List (UCL) including its seven subscales, and Illness Cognition Questionnaire (ICQ) with its three subscales. Psychological factors with a bivariate correlation with VAS(Spasticity) of p < 0.2 were selected for regression analyses. RESULTS: Nineteen patients with SCI (response rate 86%) participated. Bivariate correlations of p < 0.2 were found between VAS(Spasticity) and VAS(Pain), UCL(Active approach), UCL(Seeking social support), UCL(Reassuring thoughts), ICQ(Acceptation), and ICQ(Helplessness). Only UCL(Reassuring) (thoughts) (Beta 0.59, p = 0.01) and ICQ(Helplessness) (Beta 0.50, p = 0.02) were retained in the multivariate model, explaining 44% of the variance in VAS(Spasticity) (R(2)(adjusted)). CONCLUSIONS: Perceived spasticity appeared associated with psychological factors in complete patients with SCI: Those with higher levels of reassuring thoughts and lower levels of helplessness reported relatively lower levels of perceived spasticity. Large prospective cohort studies are recommended. PMID- 20302445 TI - A description and evaluation of an innovative rural rehabilitation programme in South Eastern Australia. AB - PURPOSE: To describe and evaluate the effectiveness of an innovative model of rehabilitation designed to meet the needs of a sparsely populated rural area in South Eastern Australia. METHOD: Five rural health services collaborated to establish a rehabilitation programme. Evaluation included comparing length of stay (LOS) and improvement in the Modified Barthel Index (BI) with the Victorian State average for Level 2 (non-specialist) rehabilitation. Surveys were conducted with staff, clients and carers in the programme. RESULTS: An inpatient rehabilitation programme was successfully established through cooperation between five health services. Clients admitted to the programme improved functionally at least as well as the Victorian State average for similar client groups (BI change 26.5 compared with 22.3 points, p < 0.001), with a shorter LOS (13.8 compared with 22.3 days) but more were discharged to residential aged care (16.1% compared with 6%). CONCLUSIONS: The programme was successful in meeting its stated aims. The model described could be adopted in rural areas sharing similar characteristics. Key enablers to the success of the programme included: collaboration between hospitals; a skilled and enthusiastic leader; recruitment of allied health staff; consistent medical leadership; access to training and support from a major regional rehabilitation centre; and access to funding to enable the programme to establish itself and demonstrate outcomes for clients. PMID- 20302446 TI - Enhanced production of red blood cells in suspension by electrostatic interactions with culture plates. AB - Enucleation of erythroblasts, a critical step in the generation of red blood cells (RBCs), occurs at a low rate without cocultured stromal cells. Previously, the surface properties of the cell culture plate were not considered in the enucleation process, because the cells exist in suspension. Here, we show that a significantly higher rate of enucleation of erythroblasts occurred on the positively charged plates than on the negatively charged surfaces or the both negatively and positively charged plates. Also, the negatively and positively charged plate group showed a significantly higher enucleation than did the hydrophobic plates. Therefore, the plates fully coated with amine groups generated 1.88 times more enucleated RBCs than did the hydrophobic plates. This study suggests an important insight into the effect of surface characteristics of cell culture plates on suspension cell culture. Further, this simple and inexpensive procedure could contribute to a more efficient RBC production system, eliminating the need for robust and expensive coculture procedures. PMID- 20302447 TI - Modern bone regeneration instead of bone transplantation: a combination of recombinant human bone morphogenetic protein-2 and platelet-rich plasma for the vertical augmentation of the maxillary bone-a single case report. AB - This publication describes the clinical case of a 75-year-old woman. She suffered from total alveolar ridge atrophy due to 20 years of wearing dentures. Bone transplantation, including harvesting of the iliac crest, was rejected by another clinic due to various existing diseases and risk of blood loss on donor side. Moreover, the minimal residual alveolar ridge did not allow bone fixation using screws nor did it allow osteodistraction. Before deciding which bone tissue engineering techniques should best be employed in this surgical treatment, cardiological and internistic consultations and treatments were carried out. In addition, anesthetic preparations were made. The surgical treatment was performed implementing special bridge flap techniques to preserve the periosteum. Tricalcium phosphate blocks soaked with recombinant human bone morphogenetic protein-2 and platelet-rich plasma were implanted on the narrow alveolar ridge. They were attached by tightening the soft tissue, including the periosteum. Four months later, after complication-free wound healing and bone regeneration, six dental implants were inserted into the new alveolar ridge. The histology of all bone samples showed vital lamellar bone. Three months after implantation, a new dental structure was fixed on the implants. The patient's quality of life improved significantly with this new situation. PMID- 20302448 TI - Relationship between competency in activities, injury severity, and post concussion symptoms after traumatic brain injury. AB - OBJECTIVE: To determine to what extent injury severity and post-concussion symptoms after 3 months predict ability in activities 12 months after traumatic brain injury (TBI) and assess the frequency of problems in daily activities. METHODS: A one-year cohort of 63 persons with mild to severe TBI was assessed on admission, after three and 12 months. Injury severity was assessed using the Glasgow Coma Scale, Abbreviated Injury Scale for the head and Injury Severity Score. Post-concussion symptoms were reported using the Rivermead Post Concussion Symptoms Questionnaire after three months. The Patient Competency Rating Scale (PCRS), a self-rating scale of ability in activities, was applied 12 months post injury. The PCRS consists of the domains interpersonal/emotional and cognitive competency, and instrumental ADL. Multiple backward regression models were performed with the three subscales of PCRS as dependent variables. RESULTS: Activity problems at 12 months were related to perceived cognitive and interpersonal/emotional competency. Post-concussion symptoms reported at three month follow-up were main predictors of cognitive and interpersonal/emotional competency at 12 months. Injury severity predicted only cognitive competency. CONCLUSION: Symptoms evolving after the trauma seem to be the strongest predictor of perceived ability in activities in this population. This underlines the need for follow-up after TBI to identify persons at risk of developing long-term activity limitations. PMID- 20302449 TI - Judicial developments in the US Hatch-Waxman infringement safe harbor. AB - Life science companies often seek guidance on whether certain current or proposed activities fall within the Hatch-Waxman safe harbor, which exempts from infringement the making, using, offering to sell or sale within the US, or the importation into the US, of "a patented invention ... solely for uses reasonably related to the development and submission of information under a Federal law which regulates the manufacture, use, or sale of drugs ...". In 2005, the US Supreme Court provided some clarity as to the scope of this safe harbor. In Merck KGaA v. Integra Lifesciences I, Ltd, the Court held that the exemption from infringement can reach certain preclinical experiments, outlining one test by which such preclinical experiments can be shown to be sufficiently 'reasonably related' to FDA submission as to qualify for the safe harbor. On remand of the case from the Supreme Court, the Court of Appeals added further explanatory detail. In late 2008, however, much of that hard-won clarity was lost when the Court of Appeals, in Proveris Scientific Corp. v. Innovasystems, Inc., addressed the 'patented invention' language of the statutory exemption, and articulated a two part test that is, in the opinion of the authors, unnecessary, unwarranted and unworkable. PMID- 20302450 TI - Estrogen receptor beta selective nonsteroidal estrogens: seeking clinical indications. AB - IMPORTANCE OF THE FIELD: Nonsteroidal estrogens have been known since the 1930s. However, the relatively recent (1996) discovery of estrogen receptor subtype beta (ERbeta) suggested a possible paradigm shift away from SERM-like selectivity. Selective ERbeta agonism would potentially allow expansion of estrogenic targeting into new indications (discussed herein) currently precluded by the thrombogenic and hyperproliferative effects of nonselective estrogens. AREAS COVERED IN THIS REVIEW: ERbeta agonist design has been very successful. Pharmacophores for ERbeta selective nonsteroidal estrogens are generally diphenolic compounds that achieve an inter-phenolic distance and geometry similar to 17beta-estradiol with few restraints on the nature of the element linking the phenols (or phenol mimetics). The tremendously chemodiverse ERbeta agonist patent literature is reviewed, segregating the agonists into structurally similar compounds based on their interphenolic linking elements. WHAT THE READER WILL GAIN: A comprehensive understanding of the chemotype landscape of this field and an assessment of its maturation. TAKE HOME MESSAGE: Subtype selective ERbeta agonist therapy seems very promising. However, more clinical testing is needed to firmly establish its therapeutic potential. At this point, ERbeta is a promising target in search of an indication. PMID- 20302451 TI - Liver X receptor modulators: a review of recently patented compounds (2007 - 2009). AB - IMPORTANCE OF THE FIELD: Liver X receptors (LXRs) are ligand activated transcription factors involved in cholesterol metabolism, glucose homeostasis, inflammation and lipogenesis. With the important physiological role of LXRs in reverse cholesterol transport (RCT), atherosclerosis is the best investigated therapeutic indication. While atherosclerosis is not yet clinically validated, Wyeth's LXRalpha/beta agonist LXR-623 indicated the key LXR target genes involved in RCT (ABCA1 and ABCG1) are upregulated in peripheral blood cells in a dose dependent manner. While discontinued for CNS safety concerns, investigation of LXR-623 supports atherosclerosis as a clinical indication, and the possibility of identifying LXR agonists with profiles that avoid the strong lipogenic effects of full LXRalpha/beta agonists. AREAS COVERED IN THIS REVIEW: Patents for LXR agonists from late 2006 up to August 2009 with emphasis on chemical matters and relationship to earlier disclosures, the biological data associated with selected analogues and therapeutic indications. WHAT THE READER WILL GAIN: An overview of the majority of LXR scaffolds with representative structure activity relationships as well as the companies that are the chief players in the field. TAKE HOME MESSAGE: The future application of LXR agonists depends upon the discovery of LXR agents without lipogenic effects. Limiting activation of LXRalpha is a popular strategy. PMID- 20302452 TI - Small molecules for bone diseases. AB - IMPORTANCE OF THE FIELD: Bones play many roles in the body, providing structure, protecting organs, anchoring muscles and storing calcium. Over 100 million people worldwide suffer from bone diseases, mainly osteoporosis, cancer-related bone loss, osteoarthritis and inflammatory arthritis. Osteoporosis itself has no specific symptoms, and the main consequence is the increased risk of bone fractures. Therefore, the prevention of bone diseases is important to maintain the quality of life in the human society. However, treatment options are still insufficient. AREAS COVERED IN THIS REVIEW: This review article gives a summary of the low molecular mass modulators of bone diseases targets disclosed in patent applications and articles, mainly during the last 5 years. WHAT THE READER WILL GAIN: Readers will rapidly gain an overview of these modulators not only for historical targets, but also of emerging and re-visited targets. Readers will also be able to see the current research trend and the main players in this field. TAKE HOME MESSAGE: Drug discovery for bone diseases has made progress in the last years. The research area has dynamically shifted from historical targets (bisphosphonate, parathyroid hormone and calcitonin) to newly confirmed targets or targets re-visited which were biologically validated in the past. Cathepsin K inhibitors should be very close to launching in the market. PMID- 20302454 TI - Cytomegalovirus vaccines and methods of production (WO20009049138): the emerging recognition of the importance of virus neutralization at the epithelial/endothelial interface. AB - Human cytomegalovirus (CMV) is the most common cause of congenital viral infection in the developed world. Approximately 40,000 congenitally infected infants are born in the US each year. Congenital CMV infection is responsible for a wide range of neurodevelopmental disabilities and is the most common infectious cause of hearing loss in children. The significant public health impact of congenital CMV has led the Institute of Medicine to rank development of a CMV vaccine as a top priority. Vaccine development has been ongoing; however, there is no licensed CMV vaccine currently available. Before vaccines can be optimized, a better understanding of how CMV infects the host is required. Recently, it has been demonstrated that CMV enters epithelial and endothelial cells by different pathways than those used for entry into fibroblasts, and that a recently described complex of CMV proteins, the gH/gL/UL128/130/131 complex, is essential for this process to occur. This discovery has allowed identification of a novel, heretofore unexplored, potential CMV vaccine targets, and provides the basis for the patent, 'Cytomegalovirus Vaccines and Methods of Production - WO2009049138.' In this patent evaluation, the basis for this patent is reviewed. The potential application of this discovery for future CMV vaccine design is discussed. PMID- 20302455 TI - Effect of plant structure on searching strategy and searching efficiency of Trichogramma turkestanica. AB - When searching for hosts on a plant, female parasitoids use strategies to maximize efficiency. Searching strategies include the expressed behaviors, the time budget associated with each behavior, the time allocated to the different plant parts and the exploration sequence of plant parts. Searching efficiency refers to the time taken to find the first egg, the number of eggs found per foraging time unit and the re-encountering frequency of eggs during a foraging period. This study examines the effect of artificial simple (few leaves and connections) and complex plant structures (more leaves and connections) on searching strategy and searching efficiency of the egg parasitoid Trichogramma turkestanica Meyer (Hymenoptera: Trichogrammatidae). Analyses of frequency and duration of behaviors associated with searching on artificial plants of different complexities were performed. Plant structure had no effect on time associated with locomotion behaviors such as walking, standing and flying. However, it had an impact on the area searched, which was significantly greater on simple plant structure. Also, time spent on a leaf without encountering an egg was greater on complex plant structure compared to simple one. No significant differences were found between simple and complex plant structures regarding time spent walking on the different plant parts such as twigs, limbs, leaf perimeters, and limbs of inferior and superior leaf sides. Results showed that female parasitoids spent less time actively exploring complex than simple plants. Encountering and re encountering frequencies of eggs were significantly greater on simple than on complex plant structure. Plant structure had no effect on handling time of eggs. This study demonstrates that plant structure can modulate activities inherent to searching and ovipositing, which in turn affects area searched per foraging time unit and therefore host finding success. PMID- 20302456 TI - The effects of hydration on growth of the house cricket, Acheta domesticus. AB - Maintenance of biochemical gradients, membrane fluidity, and sustained periods of activity are key physiological and behavioral functions of water for animals living in desiccating environments. Water stress may reduce the organism's ability to maintain these functions and as such, may reduce an organism's growth. However, few studies have examined this potential effect. The effects of altered hydration state of the house cricket, Acheta domesticus L. (Orthoptera: Gryllidae) on individual growth were studied under laboratory conditions. Crickets were permitted access to water for three different durations each day, resulting in significant differences in hydration state (32% greater hydration for maximum than minimum duration of water availability). Growth was 59% and 72% greater in dry mass and length, respectively, between the lowest and highest hydration state treatments. These findings may be representative for a variety of animal species and environments and could have important ecological implications. PMID- 20302457 TI - Army ants as research and collection tools. AB - Ants that fall prey to the raids of army ants commonly respond by evacuating their nests. This documented behavior has been underexploited by researchers as an efficient research tool. This study focuses on the evacuation response of the southwestern desert ant Aphaenogaster cockerelli Andre (Hymenoptera: Formicidae) to the army ant Newamyrmex nigrescens Cresson. It is shown that army ants can be used to collect mature colonies of ants. The applicability of this tool to ecologically meaningful areas of research is discussed. PMID- 20302458 TI - Host plant record for the fruit flies, Anastrepha fumipennis and A. nascimentoi (Diptera, Tephritidae). AB - The first host plant record for Anastrepha fumipennis Lima (Diptera: Tephritidae) in Geissospermum laeve (Vell.) Baill (Apocynaceae) and for A. nascimentoi Zucchi found in Cathedra bahiensis Sleumer (Olacaceae) was determined in a host plant survey of fruit flies undertaken at the "Reserva Natural da Companhia Vale do Rio Doce". This reserve is located in an Atlantic Rain Forest remnant area, in Linhares county, state of Espirito Santo, Brazil. The phylogenetic relationships of Anastrepha species and their hosts are discussed. The occurrence of these fruit fly species in relation to the distribution range of their host plants is also discussed. PMID- 20302459 TI - Critical feeding periods for last instar nymphal and pharate adults of the whiteflies, Trialeurodes vaporariorum and Bemisia tabaci. AB - A critical feeding period is the time after which 50% of a given species of insect can be removed from its food source and complete development by undergoing adult eclosion. The critical feeding period was determined for the greenhouse white fly, Trialeurodes vaporariorum, and the sweet potato whitefly, Bemisia tabaci (Biotype B) (Homptera/Hemiptera: Aleyrodidae). Fourth (last) instar and pharate adult whiteflies were removed from green bean leaves, staged, placed on filter paper in small Petri dishes containing drops of water, and observed daily for eclosion. For T. vaporariorum reared at 25 degrees C and L:D 16:8, 55 and 80% adult eclosion were observed when whiteflies were removed at stages 4 (0.23-0.26 mm in body depth) and 5 (> or = 0.27 mm in body depth), respectively, so that at least 50% eclosion was only achieved in this species of whitefly when adult eye development had already been initiated (in Stage 4), and 80% eclosion when adult wing development had been initiated (Stage 5). In contrast, 63% of B. tabaci emerged as adults if removed from the leaf at Stage 3 (0.18-0.22 mm in body depth), and 80% emerged if removed at Stage 4/5, stages in which adult formation had not yet been initiated. The mean number of eggs laid by experimental (those removed at Stages 4-5, 6-7 or 8-9) and control (those that remained on the leaf prior to eclosion) whiteflies, and the mean percent hatch of these eggs were not significantly different in experimental and control groups. Stages 7, 8 and 9 are characterized by a light red adult eye, medium red bipartite adult eye and dark red or red-black bipartite adult eye, respectively. Mean adult longevity also was not significantly different between experimental and control groups. However, for all groups of T. vaporariorum, adult female longevity was significantly (at least 2 times) greater than male longevity. Our results identify the critical feeding periods for last instar/pharate adults of two important pest species of whitefly. Since in both species of whitefly the critical feeding period is achieved when weight gain reaches a plateau, it appears that the critical feeding period is more closely correlated with the attainment of a critical weight than with either the time that ecdsyteroid titers first peak or the time when adult development is initiated. PMID- 20302460 TI - Humidity detection and hygropreference behavior in larvae of the tobacco hornworm, Manduca sexta. AB - Water is a critical resource for any terrestrial animal, especially for a soft bodied insect such as larvae of the tobacco hornworm, Manduca sexta L. (Lepidoptera: Sphingidae). Strategies for coping with a dry environment might include seeking out regions of high relative humidity that reduce desiccative stress, or to find and imbibe liquid water. Desiccated larvae placed in a linear arena with a humidity gradient preferred the humid end, whereas un-desiccated larvae did not. This behavior was not affected by temperature. Ablation or occlusion of the antennae showed that they are required to mediate this behavior. A series of experiments showed that control larvae oriented towards and imbibed liquid water whereas those whose antennae had been occluded with wax did not. Electrophysiological recordings from the lateral basiconic sensillum of the second antennal segment revealed the presence of at least one hygroreceptive unit that greatly increased its firing rate in response to moist air, decreased firing rates in response to dry air, and showed mild post-stimulatory inhibition. PMID- 20302461 TI - The basic helix-loop-helix transcription factor family in the honey bee, Apis mellifera. AB - The basic helix-loop-helix (bHLH) transcription factors play important roles in a wide range of developmental processes in higher organisms. bHLH family members have been identified in a dozen of organisms including fruit fly, mouse and human. In this study, we identified 51 bHLH sequences in silico in the honey bee, Apis mellifera L. (Hymenoptera: Apidae), genome. Phylogenetic analyses revealed that they belong to 38 bHLH families with 21, 11, 9, 1, 8 and 1 members in high order groups A, B, C, D, E and F, respectively. Using phylogenetic analyses, all of the 51 bHLH sequences were assigned to their corresponding families. Genes that encode ASCb, NeuroD, Oligo, Delilah, MyoRb, Figa and Mad were not found in the honey bee genome. The present study provides useful background information for future studies using the honey bee as a model system for insect development. PMID- 20302462 TI - Distribution of neuropeptide F-like immunoreactivity in the Eastern Subterranean termite, Reticulitermes flavipes. AB - The nervous system and gut of worker, soldier and alate castes of the eastern subterranean termite, Reticulitermes flavipes Kollar (Isoptera: Rhinotermitidae) were examined for immunoreactivity to an antiserum to Helicoverpa zea (Boddie) (Leipidoptera: Noctuidae) MP-I (QAARPRF-NH(2)), a truncated form of neuropeptide F. More than 145 immunostained axons and cell bodies were seen in the brain and all ganglia of the ventral nerve cord. Immunoreactive axons exiting the brain projected anteriorly to the frontal ganglion and posteriorly to the corpora cardiaca and corpora allata. In the stomatogastric nervous system, immunoreactive axons were observed over the surface of the foregut, salivary glands, midgut and rectum. These axons originated in the brain and from 15-25 neurosecretory cells on the foregut. Staining patterns were consistent between castes, with the exception of immunostaining observed in the optic lobes of alates. At least 600 immunoreactive endocrine cells were evenly distributed in the midguts of all castes with higher numbers present in the worker caste. Immunostaining of cells in the nervous system and midgut was blocked by preabsorption of the antiserum with Hez MP-I but not by a peptide having only the RF-NH(2) in common. This distribution suggests NPF-like peptides coordinate feeding and digestion in all castes of this termite species. PMID- 20302463 TI - Anthropogenic impacts on aquatic insects in six streams of South Western ghats. AB - Diversity patterns of aquatic insects among sampling sites lying with!c the unprotected and protected areas of Western Ghats were studied. This study primarily emphasizes whether anthropogenic influence is the prime cause for the presence of aquatic insects especially of pollution-sensitive organisms belonging to the orders Ephemeroptera, Plecoptera and Trichoptera, or to factors such as the physico-chemical features of the water, or sampling methods. Six streams were sampled quantitatively, of which three streams (Abbifalls, Monkey falls and Silver Cascade) were within protected areas and the remaining three streams (Kumbakarai, Shenbagadevi and Manimutharu falls) were in unprotected areas. A total of 3,209 individual aquatic insects belonging to 25 genera, 18 families and 7 orders were collected. The highest species richness and abundance was observed in Monkey falls followed by Kumbakkarai falls. Large numbers of more habitat sensitive organisms such as Ecdyonurus sp., Epeorus sp., Thalerosphyrus sp., Euthraulus sp., and Nathanella sp., were found in Monkey falls. Though the species assemblage was somewhat different, pollution-sensitive taxa were also observed in Kumbakkarai falls. Shenbagadevi and Manimutharu falls had a lower diversity of aquatic insects. The likely causes of these differences are discussed. PMID- 20302464 TI - Rearing the cotton bollworm, Helicoverpa armigera, on a tapioca-based artificial diet. AB - The impact of a tapioca-based artificial diet on the developmental rate, life history parameters, and fertility was examined over five consecutive generations for the cotton bollworm, Helicoverpa armigera Hubner (Lepidoptera: Noctuidae), a highly polyphagous pest of many agricultural crops. The study showed that when fed the tapioca-based artificial diet during larval stage, larval and pupal developmental period, percent pupating, pupal weight, emergence rate of male and female, longevity, fecundity and hatching were non-significantly different than that of the control agar-based artificial diet. Moreover, the cost to rear on tapioca-based diet approached 2.13 times less than the cost of rearing on the agar-based artificial diet. These results demonstrate the effectiveness and potential cost savings of the tapioca-based artificial diet for rearing H. armigera. PMID- 20302511 TI - Plasminogen hydrolysis by cathepsin S and identification of derived peptides as selective substrate for cathepsin V and cathepsin L inhibitor. AB - Plasminogen is a glycoprotein implicated in angiogenesis and fibrin clot degradation associated with the release of angiostatin and plasmin activation, respectively. We have recently reported that cathepsin V, but not cathepsins L, B, and K, can release angiostatin-like fragments from plasminogen. Here, we extended the investigation to cathepsin S which has been implicated in angiogenesis and tumor cell proliferation. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis of plasminogen hydrolysis by cathepsin S revealed generation of two fragments (60 and 38 kDa). Amino-terminal sequencing indicated that cleavage occurs at the Leu469-Leu470 peptide bond. In contrast to cathepsin V, which possesses antiangiogenic activity, cathepsin S plasminogen cleavage products were not capable of inhibiting angiogenesis on endothelial cells. Moreover, we explored the different selectivities presented by cathepsins V and S towards plasminogen and synthesized fluorescence resonance energy transfer peptides encompassing the hydrolyzed peptide bonds by both enzymes. The peptide Abz-VLFEKKQ-EDDnp (Abz=ortho-aminobenzoic acid; EDDnp= N-[2,4 dinitrophenyl]ethylenediamine), hydrolyzed by cath-epsin V at the Phe-Glu bond, is a selective substrate for the enzyme when compared with cathepsins B, L, and S, whereas Abz-VLFEKKVYLQ-EDDnp is an efficient cathepsin L inhibitor. The demonstrated importance of the S(3)'-P(3)' interaction indicates the significance of the extended subsites for enzyme specificity and affinity. PMID- 20302512 TI - Differential role of cathepsins B and L in autophagy-associated cell death induced by arsenic trioxide in U87 human glioblastoma cells. AB - Arsenic trioxide (arsenite) was the first chemotherapeutic drug to be described and is now being rediscovered in cancer treatment, including glioblastoma multiforme. Arsenite toxicity triggers autophagy in cancer cells, although final stages of the process involve executive caspases, suggesting an interplay between autophagic and apoptotic pathways that awaits to be explained at a molecular level. We evaluated the contribution of the lysosomal cathepsins (Cat) L and B, which are upregulated in glioblastomas, in the mechanism of arsenite toxicity in human glioblastoma cells. Arsenite treatment induced autophagosome formation and permeabilization of mitochondria, followed by caspase 3/7-mediated apoptosis. The autophagy inhibitor 3-methyladenine protected from arsenite toxicity, whereas bafilomycin A1 did not. Furthermore, arsenite significantly decreased CatB levels and selectively inhibited its cellular and recombinant protein activity, while not affecting CatL. However, downregulation of CatL greatly enhanced apoptosis by arsenite. Our results show that arsenite toxicity involves a complex interplay between autophagy and apoptosis in human glioblastoma cells and is associated with inhibition of CatB, and that this toxicity is highly exacerbated by simultaneous CatL inhibition. The latter points to a synergy that could be used in clinical treatment to lower the therapeutic dose, thus avoiding the toxic side effects of arsenite in glioblastoma management. PMID- 20302513 TI - Detection and in-cell selectivity profiling of the full-length West Nile virus NS2B/NS3 serine protease using membrane-anchored fluorescent substrates. AB - Flaviviral NS2B/NS3 heterocomplex serine proteases are a primary target for anti flavivirus drug discovery. To gain insights into the enzymatic properties and molecular determinants of flaviviral NS2B/NS3 protease substrate specificity in host cells, we developed and applied a novel series of membrane-anchored red shifted fluorescent protein substrates to detect West Nile virus (WNV) NS2B/NS3 endoproteolytic activity in human cells. The substrate consists of a fluorescent reporter group (DsRed) tethered to the endoplasmic reticulum membrane by a membrane-anchoring domain. Between the two domains is a specific peptide linker that corresponds to the NS2A/NS2B, NS2B/NS3, NS3/NS4A, and NS4B/NS5 protein junctions within the WNV polyprotein precursor. When the protease cleaves the peptide linker, the DsRed reporter group is released, changing its localization in the cell from membrane-bound punctate perinuclear to diffuse cytoplasmic. This change in protein location can be monitored by fluorescent microscopy, and cleavage products can be quantified by Western blotting. Our data demonstrate the robustness of our trans-cleavage fluorescence assay to capture single-cell imaging of membrane-associated WNV NS2B/NS3 endoproteolytic activity and to perform in-cell selectivity profiling of the NS2B/NS3 protease. Our study is the first to provide cellular insights into the biological and enzymatic properties of a prime target for inhibitors of WNV replication. PMID- 20302514 TI - Zinc supplement greatly improves the condition of parkin mutant Drosophila. AB - Parkinson's disease (PD) is a progressive neurodegenerative disorder in which oxidative stress is implicated as a major causative factor. Mutations in the gene encoding Parkin, a ubiquitin ligase, are responsible for a familial form of PD. In a Drosophila disease model lacking Parkin (park(25) null mutant), we tested the effect of zinc supplementation. Zinc is an essential trace metal and a component of many enzymes and transcriptional regulators. Unlike copper and iron, zinc is not redox-active and under most conditions serves as an antioxidant. We find that the condition of parkin mutants raised on zinc-supplemented food is greatly improved. At zinc concentrations where controls begin to show adverse effects as a result of the metal supplement, parkin mutants perform best, as manifested in a higher frequency of reaching adulthood, extended lifespan and improved motoric abilities. PMID- 20302515 TI - The molecular biology of moenomycins: towards novel antibiotics based on inhibition of bacterial peptidoglycan glycosyltransferases. AB - Moenomycins are phosphoglycolipid antibiotics and the only known natural product inhibitors of peptidoglycan glycosytransferases (PGTs). Techniques that would allow facile diversification of the moenomycin structure would facilitate the development of novel antibiotics, which are urgently needed in the wake of multidrug resistant bacterial infections. The cloning and initial characterization of the moenomycin biosynthetic genes has already redefined the minimal moenomycin pharmacophore and now opens the door for the biocombinatorial generation of bioactive moenomycin fragments. Here, we highlight the importance of research on the genetic mechanisms that regulate moenomycin biosynthesis and that confer moenomycin resistance to bacteria in the development of novel anti infectives based on PGT inhibition. PMID- 20302516 TI - Role of N-acetyl-N-nitroso-tryptophan as nitric oxide donor in the modulation of HIF-1-dependent signaling. AB - N-Acetyl-N-nitroso-tryptophan (NANT) is well known for its capacity to generate nitric oxide (NO)-releasing compounds. It is unknown, however, whether NANT can be successfully applied as a precursor of NO in a complex biological environment such as a cell culture system. NO donors can be useful to induce the transcription factor hypoxia-inducible factor 1 (HIF-1) that coordinates the protection of cells and tissues from the lack of oxygen, termed hypoxia. HIF-1 degradation is controlled by prolyl hydroxylase 2 (PHD2) which needs to be inhibited for HIF-1 accumulation. Here, the effects of NANT in inhibiting recombinant PHD2 and up-regulating of HIF-1 and HIF-1-mediated carboanhydrase-9 (CA9) mRNA expression were compared in living cells with the NO donors N nitrosomelatonin (NOMela) and S-nitrosoglutathione (GSNO) under normoxic and hypoxic conditions. In contrast to GSNO, NANT was similar to NOMela being highly effective in inhibiting recombinant PHD2. NANT-mediated activation of HIF-1 in oxygenated cells was comparable to hypoxic activation of HIF-1 in all cases. In contrast, under hypoxia NANT was able to boost hypoxic cellular HIF-1 levels by further reducing the activity of cellular PHD2. The strong increase of HIF dependent CA9 mRNA expression demonstrated that NANT-induced HIF-1 was transcriptionally active. Finally, the efficacy of NANT to increase both HIF-1 and CA9 mRNA did not depend on the absolute conformation of the tryptophan moiety. In conclusion, NANT appears to be an excellent NO donor for cells in culture and l-NANT should be useful for in vivo animal studies. PMID- 20302517 TI - Interdependence of kallikrein-related peptidases in proteolytic networks. AB - Human kallikrein-related peptidases (KLKs) are 15 homologous serine proteases involved in several (patho)physiological processes, including cancer. Secreted as precursors, they are activated upon proteolytic release of a short pro-peptide. We searched for interconnection of KLKs within extracellular proteolytic networks leading to activation of protease zymogens and found that (i) pro-KLK activation by other KLKs is scarce, with the exception of pro-KLK11, which is efficiently activated by KLK4 and 5; (ii) pro-KLK4 is activated by matrix metalloproteinase 3; and (iii) trypsin-like KLKs efficiently activate the serine protease urokinase. Our observations provide new insights into the regulation of these important tumor-associated proteases. PMID- 20302518 TI - Kallikrein-related peptidase genes as promising biomarkers for prognosis and monitoring of human malignancies. AB - Tissue kallikrein (KLK1) and the kallikrein-related peptidase (KLK2-15) genes encode for a subgroup of 15 homologous secreted serine proteases possessing numerous physiological roles, such as the regulation of blood pressure, hormone processing and tissue remodeling. The expression of KLKs is detected in a broad spectrum of human tissues where it has been found to be regulated mainly by steroids hormones. The aberrant expression of KLKs, presented in many human malignancies, highlights the significance of this gene family for early diagnosis, prognosis and monitoring of cancer patients, as it is strongly emphasized by the routine use of PSA (KLK3) for prostate cancer management. Here, we review the presently known data regarding the role of KLKs as cancer biomarkers, giving emphasis on novel information about the subject. PMID- 20302519 TI - The role of salivary histatin and the human cathelicidin LL-37 in wound healing and innate immunity. AB - Antimicrobial peptides are multifunctional in innate immunity and wound repair of multicellular organisms. We were the first to discover that histatins, a family of salivary antimicrobial peptides, enhance epithelial cell migration, suggesting a role in oral wound healing. It is unknown whether histatins display innate immunity activities, similar to other antimicrobial peptides such as LL-37. Therefore, we compared the effect of Histatin-2 and LL-37 on several activities within the context of wound healing and innate immunity. We found that Histatin-2 enhances fibroblast migration, but only weakly induces proliferation. LL-37 enhances both fibroblast migration and proliferation, but only at a narrow concentration optimum (approximately 1 microm). At higher concentrations LL-37 causes cell death, whereas Histatin-2 is not cytotoxic. Both peptides do not alter fibroblast-to-myofibroblast differentiation. Histatin-2 does not alter interleukin-8 (IL-8) expression and lipopolysaccharide (LPS)-elevated cytokine and chemokine expression. In contrast, LL-37 induces IL-8 expression, but dampens the LPS-induced immune response. Neither Histatin-2 nor LL-37 affects human neutrophil migration. Histatins are, unlike other antimicrobial peptides, not cytotoxic or proinflammatory. It seems that they are important for the initial stage of wound healing in which fast wound coverage is important for healing without infection, inflammation, or fibrosis development. Interestingly, these characteristics are more typical for the mouth than for skin. PMID- 20302520 TI - Chaperone-assisted degradation: multiple paths to destruction. AB - Molecular chaperones are well known as facilitators of protein folding and assembly. However, in recent years multiple chaperone-assisted degradation pathways have also emerged, including CAP (chaperone-assisted proteasomal degradation), CASA (chaperone-assisted selective autophagy), and CMA (chaperone mediated autophagy). Within these pathways chaperones facilitate the sorting of non-native proteins to the proteasome and the lysosomal compartment for disposal. Impairment of these pathways contributes to the development of cancer, myopathies, and neurodegenerative diseases. Chaperone-assisted degradation thus represents an essential aspect of cellular proteostasis, and its pharmacological modulation holds the promise to ameliorate some of the most devastating diseases of our time. Here, we discuss recent insights into molecular mechanisms underlying chaperone-assisted degradation in mammalian cells and highlight its biomedical relevance. PMID- 20302521 TI - Performance of host-races of the fruit fly, Tephritis conura on a derived host plant, the cabbage thistle Cirsium oleraceum: implications for the original host shift. AB - The thistle-infesting fruit fly Tephritis conura Loew (Diptera: Tephritidae) forms host races on the melancholy thistle, Cirsium hetewphyllum (L.) Hill (Asterales: Asteraceae) and the cabbage thistle, Cirsium olemceum (L.). Scop. Previous research indicates that the host shift occurred from C. hetewphyllum to C. oleraceum. In this paper we address whether the host shift involved physiological adaptations by studying oviposition acceptance and survival of the two host races on the derived host C. oleraceum. Performance differed significantly between host races. T. conura originating from C. oleraceum produced adults in 75% of all egg-laying trials in contrast to only 6.6% in T. conura originating from C. hetewphyllum. Population fitness components measured as a function of life-stage was linear decreasing for T. conura on C. oleraceum but stepwise for T. conura on C. heterophyllum. Low performance of T. conura on C. hetewphyllum was determined by low plant acceptance and high mortality during the larval stage, whereas hatching (at least one larva per batch) and pupae survival were not affected. PMID- 20302522 TI - Heat treatment of the Adzuki bean borer, Ostrinia scapulalis infected with wolbachia gives rise to sexually mosaic offspring. AB - A maternally inherited intracellular bacterium, Wolbachia, causes reproductive alterations in its arthropod hosts. In the adzuki bean borer, Ostrinia scapulalis (Walker) (Lepidoptera: Crambidae), naturally-occurring Wolbachia selectively kills male progeny. This Wolbachia strain appears to have a feminizing effect, since antibiotic treatment of infected female moths gives rise to male progeny with sexually mosaic phenotypes. It is proposed that male-specific death occurs through the feminizing effect, and sexual mosaics are produced when this effect is incompletely exerted. Here we examined whether the treatment of infected female moths with high temperatures (34 degrees C, 36 degrees C, or 38 degrees C), which is likely to suppress the activity of Wolbachia, induces sexually mosaic progeny. It was found that eggs laid within 24 h after treatment of Wolbachia-infected mothers at 36 degrees C gave rise to seven sexual mosaics along with 54 normal females. The time lag between treatment and the appearance of mosaic progeny was much shorter with heat treatment than antibiotic treatment, suggesting that heat treatment is more useful for spotting developmental timing when Wolbachia exerts its feminizing effect on O. scapulalis embryos. PMID- 20302523 TI - FMRFamide-like immunoreactivity in the central nervous system and alimentary tract of the non-hematophagous blow fly, Phormia regina, and the hematophagous horse fly, Tabanus nigrovittatus. AB - FMRFamide-related peptides (FaRPs) are a diverse and physiologically important class of neuropepeptides in the metazoa. In insects, FaRPs function as brain-gut neuropeptides and have been immunolocalized throughout the nervous system and alimentary tract where they have been shown to affect feeding behavior. The occurrence of FMRFamide-like immunoreactivity (FLI) was examined in the central nervous system and alimentary tract of non-hematophagous blow fly, Phormia regina Meigen (Diptera: Calliphoridae), and the hematophagous horse fly, Tabanus nigrovittatus Macquart (Diptera:Tabanidae). Although the central nervous system and alimentary anatomy differ between these two dipteran species, many aspects of FLI remain similar. FLI was observed throughout the central and stomatogastric nervous systems, foregut, and midgut in both flies. In the central nervous system, cells and processes with FLI occurred in the brain, subesophageal ganglion, and ventral nerve cord. FLI was associated with neurohemal areas of the brain and ventral nerve cord. A neurohemal plexus of fibers with FLI was present on the dorsal region of the thoracic central nervous system in both species. In the gut, processes with FLI innervated the crop duct, crop and anterior midgut. Endocrine cells with FLI were present in the posterior midgut. The distribution of FLI in these two flies, in spite of their different feeding habits, further supports the role of FaRPs as important components of the braingut neurochemical axis in these insects and implicates FaRPs as regulators of insect feeding physiology among divergent insect taxa. PMID- 20302524 TI - Cloning and phylogenetic analysis of sid-1-like genes from aphids. AB - Abstract The sid-1 (systemic interference defective) gene encodes a transmembrane protein that is an important participator in the systemic RNAi pathway and has been reported in several organisms. In insects, sid-1-like genes were described from Tribolium castaneum, Apis mellifera, Bombyx mori and Schistocerca americana, but were not found in Drosophila melanogaster and Anopheles gambiae. To investigate whether this gene occurs in aphid species, RT-PCRs were performed using degenerate primers designed using the conserved motif of sid-1-like genes. An sid-1-like full-length transcript was amplified from the cotton/melon aphid, Aphis gossypii Glover (Homopera: Aphididae), and a fragment was amplified from the grain aphid, Sitobion avenae (F.). The transcript from A. gossypii was 3067 bp long, with an open reading frame encoding 766 amino acids. Sequence analysis indicated that this transcript shares highest similarity with the reported sid-1 like gene in Schistocerca americana (53%, fragment), followed by A. mellifera (44%), T. castaneum (32-44%), B. mori (38-42%) and Caenorhabditis elegans (25%). Analysis of the transmembrane protein topological structure indicated that the protein encoded by this gene has a similar structure to SID-1 of C. elegans. A phylogenetic tree with all available sid-1-like genes suggests that sid-1-like genes may have had a long evolutionary history. Considering its importance in the RNAi pathway, the absence of a sid-1-like gene in D. melanogaster and A. gambiae is worthy of further investigation. PMID- 20302525 TI - Habitat preferences of butterflies in the Bumbuna Forest, Northern Sierra Leone. AB - The habitat preferences of the butterfly fauna were studied in the Bumbuna Forest Reserve in northern Sierra Leone. The intact forest reserve and a secondary forest regrowth, disturbed as a result of slash-and-burn agriculture, were compared to savanna habitats. Of the 290 specimens collected, 195 butterfly species were included, of which significant proportion were Nymphalidae. Of the 147 forest species, 111 (75.5%) showed preferences for the forest habitats, while 70 (47.6%) and 34 (23.1%) preferred disturbed and savannah habitats, respectively. Numerically, a comparable proportion of savannah species were recorded in the 18 disturbed (73.9%) and 16 savannah habitats (63.2%). Accumulated species richness and diversity indices were lower in the disturbed habitats compared to the forest reserve, but lowest in the savanna habitats. However, a large proportion of forest species, especially those with either a more restricted geographic range or species for which no information on geographic distribution was available, were exclusively captured in the forest patches. The survey indicated the presence of a rich butterfly fauna, which should be systematically collected for further research and study in order to build a good taxonomic database for Sierra Leone. PMID- 20302526 TI - Trophic interactions between two herbivorous insects, Galerucella calmariensis and Myzus lythri, feeding on purple loosestrife, Lythrum salicaria, and two insect predators, Harmonia axyridis and Chrysoperla carnea. AB - The effects of two herbivorous insects, Galerucella calmariensis Duftschmid and Myzus lythri L. (Coleoptera: Chrysomelidae), feeding on purple loosestrife, Lythrum salicaria L. (Myrtiflorae: Lythraceae), were measured in the presence of two insect predators, Harmonia axyridis Pallas (Coleoptera: Coccinellidae) and Chrysoperla carnea (Stephens) (Neuroptera: Chrysopidae). A greenhouse cage experiment examined the direct effects of these predators on these herbivores, and indirect effects of predation on aboveground biomass, defoliation, number of leaves, and internode length. Eight treatment combinations with G. calmariensis, M. lythri, H. axyridis and C. carnea were applied to caged L. salicaria. The experiment ended when G. calmariensis adults were observed, 11 to 13 days after release of first instar G. calmariensis. G. calmariensis larvae alone removed significant amounts of leaf tissue and reduced the number of L. salicaria leaves. Predators did not reduce levels of defoliation by G. calmariensis. C. carnea had no effect on G. calmariensis survival, but H. axyridis reduced G. calmariensis survival in the presence of M. lythri. Both predators reduced the survival of M. lythri. This short duration greenhouse study did not demonstrate that predator prey interactions altered herbivore effects on L. salicaria. PMID- 20302527 TI - 7th International Workshop on the Molecular Biology and Genetics of the Lepidoptera August 20-26, 2006, Orthodox Academy of Crete, Kolympari, Crete, Greece. PMID- 20302528 TI - Phylogenetic relationships of tribes within Harpalinae (Coleoptera: Carabidae) as inferred from 28S ribosomal DNA and the wingless gene. AB - Harpalinae is a large, monophyletic subfamily of carabid ground beetles containing more than 19,000 species in approximately 40 tribes. The higher level phylogenetic relationships within harpalines were investigated based on nucleotide data from two nuclear genes, wingless and 28S rDNA. Phylogenetic analyses of combined data indicate that many harpaline tribes are monophyletic, however the reconstructed trees showed little support for deeper nodes. In addition, our results suggest that the Lebiomorph Assemblage (tribes Lebiini, Cyclosomini, Graphipterini, Perigonini, Odacanthini, Lachnophorini, Pentagonicini, Catapiesini and Calophaenini), which is united by a morphological synapomorphy, is not monophyletic, and the tribe Lebiini is paraphyletic with respect to members of Cyclosomini. Two unexpected clades of tribes were supported: the Zuphiitae, comprised of Anthiini, Zuphiini, Helluonini, Dryptini, Galeritini, and Physocrotaphini; and a clade comprised of Orthogoniini, Pseudomorphini, and Graphipterini. The data presented in this study represent a dense sample of taxa to examine the molecular phylogeny of Harpalinae and provide a useful framework to examine the origin and evolution of morphological and ecological diversity in this group. PMID- 20302530 TI - Screwworms, Cochliomyia hominivorax, reared for mass release do not carry and spread foot-and-mouth disease virus and classical swine fever virus. AB - Experiments were done to determine if transporting live screwworms Cochliomyia hominivorax Coquerel (Diptera: Calliphoridae) for developing new strains from countries where foot-and-mouth disease and classical swine fever are endemic, to the mass rearing facilities in Mexico and Panama, may introduce these exotic diseases into these countries. Are screwworms capable of harboring and spreading foot-and-mouth disease virus (FMDV) and classical swine fever virus (CSFV) when they are grown in virus-inoculated larval rearing medium? In one experiment, screwworm larvae were reared in a FMDV-inoculated artificial medium containing either 0.1 % formaldehyde or antibiotics as an antimicrobial agent. In another experiment, larvae were similarly reared in a CSFV-inoculated artificial medium containing 0.1% formaldehyde. In each experiment, samples of larvae and the rearing media were collected daily until pupation occurred. The presence of FMDV was assayed by observing cytopathic effects on cell cultures and a conventional reverse transcription-polymerase chain reaction (RT-PCR); CSFV was assayed using an avidin-biotin complex assay and a conventional RT-PCR. For media containing antibiotics, FMDV was detected in a larval sample collected on day 1 and in media samples on days 1, 2 and 3. No FMDV was detected from larval and media samples collected on all other days. For media containing formaldehyde, FMDV and CSFV were not detectable in larval or media samples collected on all sampling days. These results indicate that FMDV and CSFV cannot survive in rearing medium containing formaldehyde as an antimicrobial agent. Therefore, insects collected in endemic regions and reared using formaldehyde-containing medium for at least one generation at the collection site should be free of FMDV and CSFV and can be transported safely to a strain development/mass rearing facility. PMID- 20302531 TI - Short-term dynamics of behavioral thermoregulation by adults of the grasshopper Melanoplus sanguinipes. AB - The short-term behavioral responses of adult grasshoppers, Melanoplus sanguinipes (F.) (Orthoptera: Acrididae), were examined after they experienced changes in microclimate when beingforced to change positions in their habitat. It was also determined if and when behavioral tactics allowed adults to achieve body temperatures within their preferred range. The preferred or set-point range, here taken as the interquartile range of temperatures selected on a laboratory thermal gradient, was estimated to be 37.4-40.5 degrees C. In the field, adults progressed through a relatively consistent daily sequence of behaviors, basking on the soil early in the day, but moving onto vegetation as temperatures increased. Although basking allowed grasshoppers to maximize body temperature within the available range, as much as 7 degrees C in excess of air temperature, they could not attain preferred body temperatures until soil surface temperatures reach about 35 degrees C. Basking was more effective in grazed than ungrazed pastures due to a lower degree of shading of the soil surface. As soil surface temperatures exceeded 35 degrees C, grasshoppers could achieve body temperatures within the preferred range by moving to the appropriate height on vegetation. These results illustrate the advantage of assessing behavior in the field in relation to preferred body temperatures determined in the laboratory. PMID- 20302532 TI - Gender perspective on quality of life, comparisons between groups 4-5.5 years after unsuccessful or successful IVF treatment. AB - OBJECTIVE: To describe and compare quality of life in men and women who had in vitro fertilization (IVF) within the Swedish public health system 4-5.5 years previously, either unsuccessfully and were subsequently living without children, or successfully, having children aged 4-5.5 years. These groups were compared to a control group of men and women with children born at the same time as in the successful group. DESIGN: Cross-sectional study. SETTING: Reproductive Unit, Sahlgrenska University Hospital, Gothenburg, Sweden. SAMPLE: Twenty-six men and 37 women in the unsuccessful group, 135 men and 154 women in the successful group and 93 men and 118 women in the control group. METHODS: Questionnaire study. The respective gender differences were studied in the control and study groups. MAIN OUTCOME MEASURES: Psychological general well-being (PGWB), sense of coherence (SOC), experience of infertility, demographic-socio-economic, and health characteristics. RESULTS: Men in the unsuccessful IVF group scored lower in total PGWB and SOC indices than the successful group men. They reported more depression, lower PGWB and lower SOC than the control group men. Women in the unsuccessful IVF group reported more anxiety, depression, and lower SOC than the successful group women and more depression and lower SOC indices than control group women. Men and women in the unsuccessful IVF group did not differ in any of the parameters. Men in the successful IVF group had higher PGWB, less signs of depression and more self-confidence than women in that group. CONCLUSION: Quality of life in men seems more negatively affected by involuntary infertility than reported in earlier studies. PMID- 20302533 TI - The effectiveness of adapted, best practice guidelines for smoking cessation counseling with disadvantaged, pregnant smokers attending public sector antenatal clinics in Cape Town, South Africa. AB - AIM AND OBJECTIVES: To evaluate the effect of a smoking cessation intervention, based on best practice guidelines on the quit rates of disadvantaged, pregnant women in Cape Town, South Africa. DESIGN: Quasi-experimental using a natural history cohort as a control group, consisting of women attending antenatal care in 2006 and an intervention cohort, attending the same clinics a year later. SETTING: Four, public sector antenatal clinics in Cape Town staffed and managed by midwives. POPULATION: Pregnant women of low socio-economic status. METHODS: The natural history cohort received usual care, whilst the intervention cohort was offered self-help quit materials in the context of brief counseling by midwives and peer counselors. Smoking behavior was measured in early, mid and late pregnancy. The equivalence of the groups in terms of smoking profile, self reported smoking and demographic variables was assessed at baseline. MAIN OUTCOME MEASURES: Quit rates measured by urinary cotinine towards the end of pregnancy (36-39 weeks gestation). RESULTS: The two cohorts were comparable at baseline. The difference in quit rates between the two cohorts in late pregnancy was 5.3% (95% CI: 3.2-7.4%, p < 0.0001) in an intention to treat analysis. There was also a significant difference in reduction of smoking of 11.8% (95% CI: 5.0-18.4%, p = 0.0006). CONCLUSION: A smoking cessation intervention based on best practice guidelines was effective among high risk, pregnant smokers in South Africa. PMID- 20302534 TI - Rebound acid hypersecretion. PMID- 20302535 TI - Terlipressin-induced hyponatremic seizure. AB - Terlipressin is a splanchnic constrictor that is used to control variceal bleeding and is considered to have a very good safety profile compared to vasopressin. However, side effects such as hyponatremia and seizure, although very rare, can occur. Recently, the authors have experienced a case of hyponatremia induced by infusion of terlipressin which resulted in generalized seizure. On admission, the patient's sodium level was 141 mmol/l but, 4 days after the initiation of terlipressin, it plummeted to 114 mmol/l, with serum osmolality also having fallen to 243 mOsm/kg. Hyponatremia could not be corrected despite correction with hypertonic saline but, after withdrawal of terlipressin, the serum sodium level showed a dramatic increase almost to the normal range the following day. Therefore, it is necessary to carefully monitor patients' electrolyte levels during the course of terlipressin therapy. PMID- 20302536 TI - The life cycle of the root borer, Oryctes agamemnon, under laboratory conditions. AB - The root borer, Oryctes agamemnon Burmeister (Coleoptera: Scarabaeidae), has become a serious pest of date palm trees in southwest Tunisia. Under natural conditions, mated females lay eggs in different parts of palm tree: between the hairy roots, all along the stem at the leaf axils and at the base of cut branches. Larvae bore into targeted places of the plant and were never seen outside. Pupation takes place in the plant and emergence of the adults begins in June. Larval feeding causes extensive damage to the respiratory roots. To examine the life cycle more closely, the O. agamemnon life cycle was studied under laboratory conditions. Different larval stages were collected from infested oases in Tozeur and placed in plastic boxes with natural food that was collected from the oases. After emergence, adults were paired in opaque plastic boxes for mating with the same food substrate which also served as an oviposition site. Eggs were collected daily and isolated in new boxes. Hatched eggs were recorded. The number of larval instars was determined by measuring the width of cephalic capsules. Under laboratory conditions (23 +/- 2'C and 55 +/- 6% RH)embryogenesis took 14.3 +/- 1.42 days and the first, second and third larval instars were 33.1 +/- 2.69, 63.88 +/- 6.6 and 118.3 +/- 13.38 days respectively. The pupal period lasted 24.1 +/- 3.02 days and the adult 65.27 +/- 9.48 days. These facts indicated that O. agamemnon is univoltine. PMID- 20302537 TI - Toxicity of thiamethoxam against Philippine subterranean termites. AB - Thiamethoxam (ACTARA 25WG) was evaluated for its termiticidal properties against three species of economically important subterranean termites (Isoptera: Termitidae) in the Philippines: Nasutitermes luzonicus Oshima, Macrotermes gilvus Hagen, and Microcerotermes losbanosensis Oshima. Results of the study indicated that exposure to soil or ingestion of paper treated with thiamethoxam at concentration above 0.41 ppm may provide an adequate chemical barrier or induce high mortality against N. luzonicus, M. gilvus and M. losbanosensis after 5-9 days. Feeding bioassays showed that thiamethoxam was not repellent to M. gilvus and M. losbanosensis but had an anti-feeding effect on N. luzonicus. PMID- 20302538 TI - Influence of temperature and humidity on the efficacy of spinosad against four stored-grain beetle species. AB - In the present work, we examined the insecticidal effect of spinosad, against adults of the lesser grain borer, Rhyzopertha dominica (F.) (Coleoptera: Bostrychidae), the rice weevil, Sitophilus oryzae (L.) (Coleoptera: Curculionidae), the confused flour beetle, Tribolium confusum Jacquelin du Val (Coleoptera: Tenebrionidae) on wheat and the larger grain borer, Prostephanus truncatus (Horn) (Coleoptera: Bostrychidae) on maize. The dose rates used were 0.01, 0.1, 0.5 and 1 ppm. The bioassays were carried out at three temperatures, 20, 25 and 30 degrees C and two relative humidity levels, 55 and 75%. Mortality of R. dominica and S. oryzae was high even at 0.01 ppm of spinosad, reaching 100% at 55% relative humidity and 30 degrees after 21 days of exposure. Generally, mortality of R. dominica, increased with temperature while for S. oryzae mortality increased with temperature and with the decrease of relative humidity. Moreover, for S. oryzae, mortality was low at 20 degrees C. In the case of T. confusum, mortality was low at doses between 0.01 and 0.5 ppm even after 21 days of exposure. At 1 ppm, mortality exceeded 90% only at 30 degrees C and only after 21 days of exposure. Mortality of P. truncatus was low on maize treated with 0.01 ppm, but increasing the dose to 0.1 ppm resulted in > 87% mortality after 14 days of exposure. In several combinations tested, spinosad efficacy notably varied according to the temperature and humidity regimes. Of the species tested, R. dominica and P. truncatus were very susceptible to spinosad, followed by S. oryzae, while T. confusum was the least susceptible. PMID- 20302539 TI - Transmission of two viruses that cause Barley Yellow Dwarf is controlled by different loci in the aphid, Schizaphis graminum. AB - Clonal populations of the aphid, Schizaphis graminum, have been separated into biotypes based on host preference and their ability to overcome resistance genes in wheat. Recently, several biotypes were found to differ in their ability to transmit one or more of the viruses that cause barley yellow dwarf disease in grain crops, and vector competence was linked to host preference. The genetics of host preference has been studied in S. graminum, but how this may relate to the transmission of plant viruses is unknown. Sexual morphs of a vector and nonvector S. graminum genotype were induced from parthenogenetic females and reciprocal crosses made. Eighty-nine hybrids were generated and maintained by parthenogenesis. Each hybrid was evaluated for its ability to transmit Barley yellow dwarf virus-PAV and Cereal yellow dwarf virus-RPV, and for its ability to colonize two wheat genotypes each expressing a different gene that confers resistance to S. graminum. The F1 genotypes were genetically variable for their ability to transmit virus and to colonize the aphid resistant wheat, but these traits were not genetically correlated. Individual F1 genotypes ranged in transmission efficiency from 0-100% for both viruses, although the overall mean transmission efficiency was similar to the transmission competent parent, indicating directional dominance. The direction of the cross did not significantly affect the vector competency for either virus, suggesting that maternally inherited cytoplasmic factors, or bacterial endosymbionts, did not contribute significantly to the inheritance of vector competency in S. graminum. Importantly, there was no genetic correlation between the ability to transmit Barley yellow dwarf virus and Cereal yellow dwarf virus-RPV in the F1 genotypes. These results taken together indicate that multiple loci are involved in the circulative transmission, and that the successful transmission of these closely related viruses is regulated by different sets of aphid genes. PMID- 20302540 TI - Occurrence of treehoppers (Hemiptera: Membracidae: Smiliinae) on oaks in delaware water gap national recreation area, 2004-2006. AB - A total of 870 treehoppers and 24 species from the tribe Smiliini (Hemiptera: Membracidae: Smiliinae) were collected from various oaks in the Delaware Water Gap National Recreation Area in 2006 using yellow sticky cards. Combining all years and collecting methods, 27 species were found in the park. A majority of the specimens collected in 2006 were males of Cyrtolobus vau and Ophiderma pubescens, as in previous years. Most of the treehoppers were caught in mid to late June, comparable to 2004 and 2005. It appears that many species are segregated either temporally or by oak group; some treehopper species show preference for either the red or white oak group rather than for one species of oak. Color photographs for 27 treehopper species (many including both sexes) are included. PMID- 20302541 TI - A new species and new synonym in Heptagenia walsh (Ephemeroptera: Heptageniidae: Heptageniinae) based on molecular and morphological evidence. AB - A new mayfly species, Heptagenia whitingi Webb & McCafferty n.sp. is described from larvae, a male subimago, a female adult, and eggs collected from large rivers in the west-central portion of North America. Larvae are differentiated from other North American Heptagenia Walsh by a pair of large, rectangular pale markings on abdominal tergum 4, and the combination of having the posterior margin of the abdominal terga with bluntly pointed spines less than half the length of the fine setae, small blunt spines on the posterior margin of the caudal filaments, and numerous rows of setae laterally on the ventral surface of the labrum. A 630 bp partial sequence of the mitochondrial gene cytochrome oxidase 1 (COI) from three specimens of H. whitingi n.sp. was compared with those of 12 specimens representing eight other North American species of Heptagenia. Intraspecific sequence divergences based on Kimura-2-parameter (K2P) distance ranged from 0-1.1%. Interspecific sequence divergence based on K2P distance ranged from 8.9-20.0%. Heptagenia whitingi n.sp. differed from its sister taxon H. flavescens (Walsh) by 11.7%. Heptagenia diabasia Burks and H. elegantula (Eaton) differed from each other by only 1.1%; these two alleged species show a clinal pattern in larval abdominal coloration and there are no structural differences between the semaphorants. On this basis, H. diabasia is placed as a junior subjective synonym of H. elegantula, n.syn. PMID- 20302542 TI - Porphobilinogen synthase from the butterfly, Pieris brassicae: purification and comparative characterization. AB - Porphobilinogen represents a key building block of tetrapyrroles serving as functional ligands of many vitally important proteins. Here we report the first purification of porphobilinogen synthase (PBGS) from whole insects by sequentially employing two modes of native electrophoresis on polyacrylamide gels subsequent to more conventional procedures. Using adults of Pieris brassicae L. (Lepidoptera: Pieridae) we achieved approximately 10,000-fold purification with final yields of up to 25% of electrophoretically pure PBGS with a specific activity of approximately 160 micromol PBG h(-1) mg(-1) at 37 degrees C and an affinity of 0.36 mM to its substrate 5-aminolevulinic acid. Enzyme activity was inhibited by the substrate mimics, levulinic acid and succinylacetone, and by chelating agents. PBGS behaved as a relatively heat-stable octameric complex of 292.3 kDa composed of 36.5 kDa subunits. Most general features of this insect PBGS were comparable to those published for other animal PBGS enzymes, while remarkable differences were found to the reported recombinant Drosophila enzyme. Moreover, rabbit antiserum directed against purified Pieris PBGS revealed significant immunological differences among insect PBGS enzymes from a wide range of orders contrasting to the overall evolutionary conserved features of this enzyme. PMID- 20302543 TI - Potentially hygroreceptive sensilla on the anal stylus of the glassy-winged sharpshooter, Homalodisca vitripennis. AB - Abstract This study begins to elucidate the cues and mechanisms by which the glassy-winged sharpshooter, Homalodisca vitripennis (Germar) (Hemiptera: Cicadellidae), select host plants for feeding and oviposition. The electrophysiological response of the anal styli of male and female H. vitripennis to water vapor was examined using a modified electroantennography (EAG) device (stylogram). A strong electrophysiological response of the anal stylus to water vapor was found. Scanning electron microscopic examination of the anal stylus revealed the presence of long mechanosensory hairs, many small coeloconic-type sensilla, and masses of secretory granules termed brochosomes. Each coeloconic sensillum is located in a pit from which protrude finger-like projections. The pit is often blocked by masses of brochosomes and an unidentified dense material. Based on the electrophysiological response of the anal stylus to water vapor, we hypothesize that the coeloconic sensilla on the stylus may be hygroreceptors. H. vitripennis are xylem feeders and may use the sensilla to assist in host selection for the purpose of feeding or oviposition based on detected plant water status. Furthermore, H. vitripennis oviposit into the leaf epidermis, and may use these sensilla to evaluate moisture content to determine host suitability for both oviposition and subsequent feeding of emerged progeny. Understanding the cues and underlying mechanisms of host selection is an important consideration for predicting the movement of H. vitripennis between crops and disease epidemiology. PMID- 20302544 TI - Reproductive tactics of sexes and fitness in the dragonfly, Diastatops obscura. AB - The sexual selection strategies of territorial Odonata that do not present courtship behavior is still not completely understood, especially the role of the females. Diastatops obscura Fabricius (Odonata: Libellulidae) females participate in mate selection in a passive manner, allowing copulation with the first male that captures them and afterwards choosing whether to oviposit or not. This study introduces the idea of female passive choice as an adaptative tactic in intersexual selection. Also discussed is the adaptative value of this tactic and its flexibility according to environmental conditions and reproductive strategies adopted by the males. A natural population of Diastatops obscura was observed in the Pitimbu River of northeast Brazil. Focal continuous and ad libitum techniques were used to record attempted copulation, copulation, and oviposition behavior, in addition to registering male territoriality. An estimate of individual reproductive success (IRS) was obtained by recording 187 reproductive events. Territorial males, mainly occupying areas near the river margin, achieved greater copulation and oviposition success (IRS = 0.371) than did satellite males (IRS = 0.028). Females that copulated with territorial males experienced, for the most part, only one copulation and oviposition event, while those that copulated with satellite males fled or performed a second copulation with a territorial male. Thus, the best tactic adopted by the D. obscura males was to occupy a territory providing the greatest access to females, while the females used passive choice for fitness optimization. PMID- 20302545 TI - Descriptive study of damage caused by the rhinoceros beetle, Oryctes agamemnon, and its influence on date palm oases of Rjim Maatoug, Tunisia. AB - Oryctes agamemnon (Burmeister 1847) (Coleoptera, Scarabaeidae) was accidentally introduced in the southwestern oases of Tunisia (Tozeur) around 1980 and spread to the Rjim Maatoug region. In these areas O. agamemnon was specific to date palm trees causing severe damage that can result in potential danger due to collapse of the tree. This study was conducted from April 2004 to March 2006 in 4 sites in the region of Rjim Maatoug. Different levels of palm tree attack were determined, ovioposition sites were identified, and pest damage was described in detail to specify their relative importance and to indicate factors governing palm tree attack. Eggs were individually oviposited in the attacked parts. Dead parts of palm trees were the main target of O. agamemnon including the respiratory roots, tough, trunk bark, dry petiole and the periphery of the crown. The crown itself was not attacked. Feeding by larvae caused significant damage. The biggest danger occurred when heavy attacks of larvae invaded the respiratory roots at the level of the soil, and secondarily on the periphery of the crown, which can result in fungal diseases. Several cases of Deglet Nour date palm tree collapse were caused by this pest in Rjim Maatoug. Attacks on other parts of the tree were without danger for the palm tree. In the absence of pest management, application of a quarantine program combined with field cultivation techniques could help farmers significantly decrease attack of O. agamemnon on palm trees. PMID- 20302546 TI - Gynomorphic mandible morphology in the dobsonfly, Corydalus cornutus. AB - Two aberrant males of Corydalus cornutus (L.) (Insecta: Megaloptera), which exhibit unusually short mandibles with discrete dentition, are recorded from a locality in Missouri. Morphological details of the specimens, as well as implications for the overall morphological variation of the genus and species are discussed. The term gynomorphic is suggested as the best descriptor of this case, given that little explanatory information is available to classify these specimens as true gynandromorphs. PMID- 20302547 TI - Rapid diagnosis of tuberculous pericarditis by ELISPOT assay. AB - We describe a case in which the rapid diagnosis of tuberculous pericarditis was made using the Mycobacterium tuberculosis (MTB)-specific enzyme-linked immunospot (ELISPOT) assay on pericardial effusion mononuclear cells (PEMCs). The analysis of MTB-specific T-cells in PEMCs by ELISPOT may be useful for rapid decision making in anti-tuberculous treatment. PMID- 20302548 TI - Prognostic value of germ cells in the ejaculate: a case study. AB - The first approach to assessing male fertility is to study a spermiogram, where special attention is given to sperm count, motility and morphology, while less attention is given to other cells in the ejaculate. Normal spermatogenesis requires a balance between cell death and proliferation; therefore, the number of germ cells (GC) in the ejaculate is less than the number of sperm. We propose a new index for altered spermatogenesis, i.e., the rate GC/sperm. We investigated a patient with oligozoospermia and a GC/sperm ratio greater than one, which indicated that spermatogenesis had been damaged. Complementary cytological tests were employed to characterized GC status: Papanicolaou stain, transmission electronic microscopy (TEM), vitality test, AgNOR and TUNEL assay. We also correlated cell morphology with ultrastructure studies that showed apoptosis. Nuclear apoptosis is characterized by vacuolization, misshapen nuclei, and "half moon," dispersed, uncondensed, disrupted and smudged chromatin. Cytoplasmic apoptosis is characterized by vacuolization, cytoplasmic protrusions, lamellar bodies, and swollen endoplasmic reticulum and mitochondria. To date, only testicular biopsy has been used to diagnose complete or incomplete testicular arrest. Our investigation is the first to determine a cytological feature in semen samples that could be used as a biological marker for abnormal spermatogenesis and for predicting the transition from oligospermia to azoospermia. PMID- 20302549 TI - Cryptococcus neoformans and Cryptococcus gattii genes preferentially expressed during rat macrophage infection. AB - Cryptococcus neoformans and Cryptococcus gattii are encapsulated yeast agents of cryptococcosis and facultative intracellular pathogens. The interaction of these yeasts with macrophages is essential for containing the infection. However, Cryptococcus spp. overcome this initial host defense barrier using a unique pathogenic strategy involving intracellular replication and cytoplasmic accumulation of polysaccharide-containing vesicles. Here, we employed representational difference analysis (RDA) to identify C. neoformans and C. gattii genes differentially expressed during intracellular growth in rat peritoneal macrophages. The upregulated transcripts of C. neoformans during macrophage interaction were related to ATP-binding cassette (ABC) transporters, intra-golgi transport, chaperone activity, ribosomal maintenance, NAD metabolism, histone methylation, stress response, and monosaccharide metabolism. In contrast, with C. gattii, upregulated genes were associated with cell growth, aerobic respiration, protein binding, microtubule nucleation, monosaccharides and nitrogen metabolism, inositol or phosphatidylinositol phosphatase activity, cellular signaling, and stress response. Our findings reveal new genes that may be necessary for the intracellular parasitism of C. neoformans and C. gattii. PMID- 20302550 TI - Fonsecaea nubica sp. nov, a new agent of human chromoblastomycosis revealed using molecular data. AB - A new species of Fonsecaea, Fonsecaea nubica, morphologically similar to F. pedrosoi and F. monophora, is described using multilocus molecular data including AFLP profiles, sequences of the ribosomal internal transcribed spacers (ITS), and partial sequences of the cell division cycle (cdc42), beta-tubulin (tub1) and actin (act1) genes. A phylogenetic approach was used to evaluate species delimitation. Topologies of the trees were concordant. Fonsecaea strains could be classified into three major entities, i.e., one representing Fonsecaea pedrosoi isolates, another consisting of strains of F. monophora, and a third, unnamed group comprising isolates mostly recovered from cases of chromoblastomycosis in South America and China. F. nubica is part of this latter group. Based on strains analyzed thus far, we have found that the pathologies of these three Fonsecaea species are somewhat different in that F. pedrosoi and F. nubica are preponderantly associated with chromoblastomycosis, while F. monophora may also act as a systemic opportunist in cases involving brain infections. The latter species is also the most frequently recovered of the three from environmental samples. PMID- 20302551 TI - Efficacy of vitamin D3 supplementation in preventing fractures in elderly women: a meta-analysis. AB - BACKGROUND: The efficacy of vitamin D(3) in preventing fractures and falls has been explored in a number of clinical trials. However, recent evidence revealed new questions about the adequate doses of vitamin D(3) supplementation and its efficacy in fracture prevention independent of calcium supplements for various types of fractures. OBJECTIVE: To conduct a meta-analysis to estimate the effectiveness of 800 IU daily vitamin D(3) supplementation for increasing bone mineral density (BMD) and preventing fractures in postmenopausal women. METHODS: Medline and EMBASE were searched for controlled trials comparing the effectiveness of cholecalciferol (vitamin D(3)) against placebo with or without background calcium supplementation in the treatment of postmenopausal women. RESULTS: Eight controlled trials evaluating the effect of vitamin D(3) supplementation with or without calcium were assessed. Of 12 658 women included in a Bayesian meta-analysis, 6089 received vitamin D(3) (with or without calcium) and 6569 received placebo (with or without calcium). Compared to placebo, vitamin D(3) with calcium supplementation showed beneficial effects on the incidence of non-vertebral (odds ratio [OR] 0.77, 95% credibility limit [CL] 0.6-0.93) and hip (OR 0.70, 95% CL 0.53-0.90) fractures, while the effects on non-vertebral-non-hip fractures (OR 0.84, 95% CL 0.67-1.04) % point increase) were associated with more uncertainty. Vitamin D(3) supplementation showed a 70% probability of being a better treatment than placebo for the prevention of non-vertebral fractures, hip fractures, and non-vertebral, non-hip fractures. Compared to calcium supplementation, vitamin D(3) plus calcium reduced non-vertebral fractures (OR 0.68, 95% CL 0.43-1.01) and non-vertebral, non-hip fractures (OR 0.64, 95% CL 0.38-0.99), but did not reduce hip fractures (OR 1.03, 95% CL 0.39-2.25). Key limitations to this analysis include a small number of studies and heterogeneity in the study populations. CONCLUSIONS: This meta-analysis supports the use of vitamin D3 of 800 IU daily to reduce the incidence of osteoporotic non-vertebral, hip, and non-vertebral-non-hip fractures in elderly women. Vitamin D(3) with calcium appears to achieve benefits above those attained with calcium supplementation alone for non-vertebral and non-vertebral-non-hip fractures. PMID- 20302552 TI - Evidence for the efficacy of ARBs across the cardiovascular continuum. AB - INTRODUCTION: Angiotensin II receptor blockers (ARBs) are antihypertensive agents with considerable evidence of efficacy and safety for the reduction of cardiovascular (CV) disease risk in numerous patient populations from one end of the CV continuum (i.e., primary prevention among patients with CV risk factors) to the other (i.e., secondary prevention in the post-MI setting). There are several agents within the ARB class, all of which have contributed to various degrees to this evidence base. SCOPE: This review presents the design and main results of large, well designed studies examining the CV risk-reducing properties of ARBs. The authors searched major literature databases (Embase, Medline, PubMed) for randomized, controlled studies published between January, 1995 and October, 2009 that compared ARBs with placebo or active controls and reported major CV outcomes (e.g., myocardial infarction, stroke) and/or mortality as the primary study endpoint(s). LIMITATIONS: Although many trials evaluating similar agents are presented, between-trial comparisons are inappropriate. The results of each study stand on their own merits and weaknesses, but do not provide any additional insight into the results of the other studies. RESULTS: Agents in the ARB class have demonstrated efficacy in reducing CV events and/or mortality in a number of different patient populations, from primary prevention studies in patients with pre-specified risk factors (e.g., hypertension and left-ventricular hypertrophy in the LIFE study) to secondary prevention (i.e., post-MI patients in the VALIANT study). Some studies have also demonstrated the statistical equivalence of ARBs to ACE inhibitors in certain populations (e.g., among post-MI patients in VALIANT and among a broad population of patients with vascular disease or diabetes in the ONTARGET). There are several major studies currently underway that will provide further information on the risk-reducing properties of ARBs in additional populations (e.g., patients with impaired glucose tolerance in the NAVIGATOR study). CONCLUSIONS: ARBs have demonstrated efficacy in reducing CV morbidity and mortality in a broad spectrum of CV disease states across the CV continuum. Ongoing research continues to provide additional evidence, with ongoing trials investigating their role in additional patient populations. PMID- 20302553 TI - Biosimilars: controversies as illustrated by rhGH. AB - Abstract Background and scope: Similar biological medicinal products, also called 'biosimilars', are copies of biopharmaceutical products whose patent has expired. Whether biosimilars are truly comparable and interchangeable with their reference biopharmaceutical products in terms of quality, efficacy and tolerability, is still a matter of debate. This review discusses the controversies related to the criteria for regulatory approval of biosimilars. These concerns are illustrated using recombinant human growth hormone (rhGH) biosimilars as an example. METHODS: Publications on the regulatory approval of biosimilars in general and rhGH biosimilars in particular were searched in MEDLINE by exploding and combining the medical subject heading terms 'human growth hormone', 'efficacy' or 'safety' and the free-text words 'biosimilar', 'biopharmaceutical', 'similar biological medicinal product', 'follow-up biologic' or 'biogeneric'. Searches were limited to full-text English-language articles. The websites from the European Medicines Agency (EMA) and from the American Food and Drug Administration were also consulted. Regulatory status: To obtain regulatory approval of a biosimilar product by EMA, demonstration of comparability with an approved reference biopharmaceutical product in terms of quality, efficacy and tolerability is needed. Thus, comparative quality studies, non-clinical and clinical efficacy and tolerability studies are required. However, in contrast to the reference product, comparative non-clinical pharmacokinetics, safety pharmacology, reproduction toxicology, mutagenicity and carcinogenicity studies are not mandatory to obtain approval of a biosimilar. In addition, comparable efficacy and tolerability only needs to be established by one study in a single population during a limited time interval (12 months) and often allows extrapolation to all other approved indications of the reference product. Consequently, for the currently approved rhGH biosimilars, long-term efficacy and tolerability in all indications has not been proven to the same degree as for the reference products. CONCLUSIONS: The validity of the current criteria for comparability and interchangeability of biosimilars and their reference products remains controversial. The authors conclude that long-term clinical investigations and systematic monitoring of the efficacy and tolerability of rhGH biosimilars in all indications are needed. In addition, the medico-economical environment should allow physicians to take a free and informed decision about the type of rhGH to be prescribed. PMID- 20302554 TI - Can we obtain hyaline cartilage with currently available techniques? PMID- 20302555 TI - Is osteoarthritis a disease involving only cartilage or other articular tissues? AB - Osteoarthritis (OA) is a progressive and disabling disease resulting from a combination of risk factors, including advancing age, genetics, trauma, knee malalignment, increased biomechanical loading of joints through obesity, augmented bone density and an imbalance in physiological processes resulting in catabolic cascades on a molecular level. This review will highlight the involvement early in the disease process of not only the cartilage but also the synovial membrane and subchondral bone and the pathophysiological mechanisms of each of these tissues that lead to joint degeneration. We will summarize the current pathological mechanisms that occur in the abovementioned articular tissues, and briefly discuss their interconnections during OA. PMID- 20302556 TI - Intermediate-term results after uncemented total hip arthroplasty for the treatment of developmental dysplasia of the hip. AB - OBJECTIVES: We aim to evaluate the restoration of the hip and limb length in patients with osteoarthritis secondary to developmental dysplasia of the hip (DDH) using total hip arthroplasty (THA). PATIENTS AND METHODS: Between February 1996 and September 2001, 65 hips in 55 patients (2 males, 53 females; mean age 48.6 years; range 37 to 60 years) with advanced osteoarthritis secondary to DDH underwent uncemented THA. According to the Hartofilakidis classification, 20, 27, and 18 hips were evaluated types I (dysplasia), II (subluxation), and III (dislocation), respectively. All of the acetabular cups were reconstructed in the original anatomic location. Structural autografts were used in seven hips to supplement the acetabular coverage. We evaluated all patients clinically and radiographically. RESULTS: All of the patients were followed up for 7-12 years. Preoperatively, the Harris score averaged 52.5, 48.41, and 45.28 in types I to III, respectively. At the final follow-up, the Harris score averaged 89.65, 87.44, and 83.28, respectively. The difference between the pre- and postoperative scores was significant (p=0.0001). Preoperatively, 26 patients (47.27%) had slight limps (length difference <1 cm), eight (14.55%) had moderate limps (length difference 1-3 cm), and 21 (38.18%) had severe limps (length difference >3 cm). At their final follow-up, four (7.27%) had severe limps. The limps of all of the patients improved significantly (McNemar's test p=0.0001). We observed aseptic loosening and subsidence in six hips. In seven hips, we used a femoral head autograft for the superior acetabular defect. We performed femoral shortening osteotomies only for two (3.07%) type III hips. CONCLUSION: In addition to the standard procedure, structural bone autografting, medialization of the cup, and placing the acetabular component in the true acetabulum are important factors for successful intermediate-term results. PMID- 20302557 TI - [Parallelism of vibration sense with proprioception sense in patients with patellofemoral pain syndrome: a pilot study]. AB - OBJECTIVES: The purpose of the study was to evaluate the utility of vibration sense as a proprioceptive test in patients with a clinical diagnosis of patellofemoral pain syndrome. PATIENTS AND METHODS: Nineteen patients with a clinical diagnosis of patellofemoral pain syndrome and 10 healthy volunteers were included in the study. Patients and volunteers underwent a joint position sense test and a vibration sense test. A digital goniometer and 128 Hz frequency tuning fork were used for the measurements. The results of the pathologic knees were compared with the results of both their contralateral knees and the normal knees of the volunteers. T-test, Mann Whitney U and Pearson correlation tests were used for statistical analysis. RESULTS: The amount of time to perceive the vibration was 7.2+/-1.3 sec for the symptomatic knees, whereas it was 9.1+/-1.5 sec for the contralateral knees (p<0.05), each in the extended position. Joint position sense testing also showed deterioration of proprioception in accordance with the vibration testing. Similar differences were obtained between the symptomatic knees and the normal knees of volunteers (p<0.05). No differences were found in vibration sense measurements done at a 90 degrees flexion position of the knee (p>0.05). CONCLUSION: The results of the study show that the amount of time a vibration could be perceived is diminished in the symptomatic knees of the patients as compared to symptomatic knees. It is possible to extrapolate from these findings that vibration perception may be used for proprioceptive measurement. PMID- 20302558 TI - [Unicondylar knee arthroplasty in medial unicompartmental osteoarthritis: technical faults and difficulties]. AB - OBJECTIVES: The aim of this study is to evaluate both the technical problems of surgery and the clinical and radiologic outcomes of patients treated with unicondylar knee arthroplasty. PATIENTS AND METHODS: Forty-one unicondylar knee prosthesis were performed in 40 patients (3 males, 37 females; mean age 58.2 years; range 44 to 76 years) diagnosed with unicompartmental knee osteoarthritis. Technical problems encountered during surgery were noted. For evaluation of clinical outcomes, the Hospital for Special Surgery (HSS) knee score and WOMAC score were used. Radiologic evaluations were performed using the Oxford Knee Group criteria. RESULTS: The radiologic evaluation determined there was more than 10 degrees varus-valgus malposition in eight patients, more than 2 mm medial tibial overhang in seven patients, the insertion of a femoral component in extension in one patient, and joint distraction in one patient. The patient with joint distraction underwent a total knee replacement after six months because of progressive pain. The mean HSS knee score improved 21 points; perfect results were obtained in 33 patients and good results in seven patients. The mean postoperative WOMAC score was reduced by 18 points, with perfect results in 33 patients, good results in six patients and a moderate result in one patient. The mean follow-up was 19 months (range 9-42). CONCLUSION: Unicondylar knee arthroplasty is a surgical treatment method with a long-term recovery and high frequency of technical faults. Minor errors diagnosed on radiographs do not have an effect on early clinical results. Unicondylar knee arthroplasty is a good alternative surgical technique for appropriately selected patients with medial unicompartmental knee osteoarthritis. PMID- 20302559 TI - The three portal (including transpatellar tendon portal) versus two portal technique in the arthroscopic menisectomy procedure for isolated medial bucket handle type meniscal tears. AB - OBJECTIVES: The aim of this study is to evaluate the efficacy of the central (transpatellar tendon) portal technique for the treatment of isolated medial bucket-handle type meniscal tears with the arthroscopic menisectomy procedure. PATIENTS AND METHODS: In this study, fifty patients with isolated medial bucket handle type meniscal tears were evaluated. They were divided into two groups with 25 patients in each group. In the first group, the three portal (including central portal) technique was used and in the second group, the two portal technique was used. The results of the two groups were compared in terms of (i) operation times; (ii) changes in Insall-Salvati ratios postoperatively; (iii) postoperative Cincinatti scores; (iv) quadriceps muscle strengths; (v) the presence of anterior knee pain and; (vi) complication rates, in order to determine the significance of adding a central portal to the standard anterolateral and anteromedial portals in the menisectomy procedure. RESULTS: There was no significant difference between the two groups in terms of Cincinnati clinical scores, quadriceps muscle strenghts and complication rates. However, the operation time values of the first group were significantly shorter than the second group (p<0.001). The postoperative changes in Insall-Salvati ratio values were significantly higher in the first group than the second group (p<0.002). This results show us that the first group had a significant decrease in patellar tendon length whereas the second group had no change in size postoperatively. CONCLUSION: We suggest that the use of the central portal for viewing and instrumentation is a safe and quick technique in the menisectomy procedure for medial bucket-handle type meniscal tears, due to its unexpected lower complication rates and shorter operation times. While it causes patellar tendon shortening, this does not effect the clinical outcomes. PMID- 20302560 TI - Double plate osteosynthesis provides better biomechanical stabilization than double tension band technique in distal humerus fractures. AB - OBJECTIVES: In this study we evaluated the stability and effectiveness of the double tension band osteosynthesis technique compared to the double plate osteosynthesis technique used for fixation of distal humerus fractures. MATERIALS AND METHODS: The study was performed on two groups, and in each group eight cadaveric, elderly (mean age 70-80) human humeri was used. An osteotomy was performed in the supracondylar region using a manual saw. The first group (group 1) was fixed with double 3.5 mm reconstruction plates, while the second group (group 2) was fixed with the double tension band technique, using crossing Kirschner wires. The osteotomy was designed so that the distal fragment would allow only a single screw per plate. The constructs were evaluated using a material testing machine. A linear non-cyclic load was applied until the failure of the constructs. The force which produced a 3 mm gap (3 mm gap strength), as detected visually with the aid of operating loupes, and the maximum load prior to failure of the fixation (maximum force) were measured from all tests. RESULTS: The mean value for the 3 mm gap strength was 1356.29+/-226.97 N for group 1 and 882.63+/-305.21 N for group 2. The mean value of the maximum load strength was 1487.13+/-298 N for group 1 and 1232+/-107.62 N for group 2. There were significant differences in 3 mm gap strengths of the two groups (p=0.005). There was also a significant difference in the maximum load between the two groups (p=0.016). CONCLUSION: Double plate osteosynthesis technique is superior to double tension band osteosynthesis for the fixation of distal humerus fractures. PMID- 20302561 TI - [Age-related changes in light microscopy with Sirius red technique in rat Achilles tendon]. AB - OBJECTIVES: In this study, age-related morphological changes in intact rat Achilles tendon was investigated. MATERIALS AND METHODS: Thirty Wistar albino rats of 2-3 weeks, six months and 12 months old groups 10 animal in each group were examined with Sirius red light microscobic staining. RESULTS: The Sirius red light microscobic staining revealed that red stained collagen fibers have a decreased waviness with more rounded appearence of tenocyte nuclei, extracellular matrix along a increased vascularity and the number of tenocytes decreased with age was statistically meaningfull. CONCLUSION: The possible causes of the spontaneously Achilles tendon rupture in adult ages group was investigated with Sirius red light microscopic technique. In this age group, initiation of the degenerative changes are decreasing the elasticity thus function of this tendon. PMID- 20302562 TI - Insufficiency femoral fractures in patients undergoing prolonged alendronate therapy. AB - A 76-year-old woman complaining of pain and swelling in her right thigh was admitted to our clinic. She had been undergoing alendronate therapy for more than 10 years. Physical examination revealed a mild swelling, pathologic motion and pain in her right thigh. Radiograms showed a transverse fracture with a medial spike in the area of thickened cortices of femoral diaphysis. She received surgical stabilization. The patient is now pain-free and she has walked with full weight bearing without any complications since the first postoperative day. Dual energy X-ray absorptiometry revealed a T-score for the lumbal spine of -2.89 and for the hip of -3.55. We stopped alendronate treatment. However the patient is receiving only calcium and vitamin D. PMID- 20302563 TI - Between bench and bed side: PI3K inhibitors. AB - The PI3K pathway constitutes an important pathway for regulating the signaling of multiple essential biological processes for which deregulation might contribute to cancer. As such, the PI3K pathway is one of the most frequently altered pathways in human tumors, providing constitutive pathway activation. The evidence indicates that the PI3K pathway is a potential target for cancer chemotherapy. Indeed, many companies and academic laboratories have initiated a variety of approaches to inhibit the pathway at different points. These proteins are kinases, which are very "druggable" targets a priori and, according to the "addiction hypothesis," cancer cells with this pathway activated will be more dependent upon this pathway for their survival. In this work, we will focus on PI3K protein as a major target for therapeutic intervention. We thoroughly review the clinical achievements and major concerns raised by the pharmacological intervention of PI3Ks. PMID- 20302564 TI - Activation of sphingosine kinase-1 in cancer: implications for therapeutic targeting. AB - Sphingolipid metabolites are critical to the regulation of a number of fundamental biological processes including cancer. Whereas ceramide and sphingosine mediate and trigger apoptosis or cell growth arrest, sphingosine 1 phosphate promotes proliferation, cell survival and angiogenesis. The delicate equilibrium between the intracellular levels of each of these sphingolipids is controlled by the enzymes that either produce or degrade these metabolites. Sphingosine kinase-1 is a crucial regulator of this two-pan balance, because its produces the pro-survival and pro-angiogenic sphingosine 1-phosphate and decreases the amount of both ceramide and sphingosine, the pro-apoptotic sphingolipids. Moreover, its gene is oncogenic, its mRNA is overproduced in several solid tumors, its overexpression protects cells from apoptosis, and its activity is down-regulated by anti-cancer treatments. Therefore, the sphingosine kinase-1/sphingosine 1-phosphate signaling pathway appears to be a target of interest for therapeutic manipulation. PMID- 20302565 TI - Potential role of acrolein in neurodegeneration and in Alzheimer's disease. AB - Lipid peroxidation leads to the formation of a number of aldehydes by-products, including acrolein. The most abundant aldehydes are 4-hydroxy-nonenal (4-HNE) and malondialdehyde (MDA) while acrolein is the most reactive. In Alzheimer's brain, acrolein was found to be elevated in hippocampus and temporal cortex where oxidative stress is high. In late onset Alzheimer's disease (AD), a 2-fold increase in levels of acrolein/guanosine adducts in nDNA were isolated from the hippocampus of AD as compared to age-matched control. These adducts are biologically relevant in that they may promote DNA-DNA and DNA-protein cross linking while 4-HNE/guanosine adduct in nDNA was not elevated in AD. In AD, the activity of the glutathione-S-transferase, the main enzyme responsible for the detoxification of acrolein is significantly decreased in hippocampus. On neuronal primary culture from hippocampus, acrolein caused cell death and its toxicity is higher than 4-hydroxynonenal. Acrolein could modulate tau phosphorylation through different pathways. Acrolein has been shown to inhibit the mitochondrial activity. Due to its high reactivity, acrolein is not only a marker of lipid peroxidation but also an initiator of oxidative stress by adducting cellular nucleophilic groups found on proteins, lipids, and nucleic acid. As a strong electrophile molecule, acrolein can react about 110-150 times faster with the thiol group of cysteine than with 4-hydroxynonenal and decrease the level of the antioxidant glutathione. Taken together, these reactions suggest that acrolein could play a role in the pathophysiology of AD. In this review, we will summarize some mechanisms implicated in the toxicity of this by-product of lipid peroxidation in brain and their implication in AD. PMID- 20302567 TI - Oxidative biotransformation of fatty acids by cytochromes P450: predicted key structural elements orchestrating substrate specificity, regioselectivity and catalytic efficiency. AB - In view of the pivotal role played by the diversity of fatty acid-derived oxy products in a vast array of physiological processes, precise knowledge about the molecular principles dictating substrate specificity and regioselectivity in P450 catalyzed oxidative attack on the distinctly structured carbon chains of the monocarboxylic acids is of paramount importance. Based on a general, CYP102A1 related construct, the majority of prospective key determinants participating in fatty acid recognition/binding were found to cluster near the distal heme face made up by the helical B', F, G and I tetrad as well as the B'-C interhelical loop and certain beta-sheet segments. Most of the contact sites examined show a frequency of conservation <10%, hinting at the requirement of some degree of conformational flexibility. Some decisive elements may also have a function in maintaining active-site integrity, governing substrate access to the catalytic centre, and steering the redox machinery to efficiently promote fatty acid oxidations. Physico-chemical factors imposing constraints on orientation of the fatty acid molecules towards the iron-oxene core focus on the variably expressed polarity profile of the diverse docking regions and bulkiness of critical amino acid side chains, acting as selectivity filters for the substrate homologues. Also, dynamic fluctuations of certain contact sites located in the distal backbone of P450s may impact fatty acid positioning. Genetic engineering to introduce versatile properties into fatty acid hydroxylases may give an impetus to biotechnological exploitation of the tailored enzymes in the production of fine chemicals and therapeutic agents. PMID- 20302568 TI - An integrated metabolomics and pharmacokinetics strategy for multi-component drugs evaluation. AB - The treatment of common multi-factorial, system-wide diseases using multi component therapeutics, such as herbal medicines, can be regarded as a "system to system" therapeutic approach. The pharmacokinetics (PK) of multi-component therapeutics is a great technical challenge, which has led to significant limitations in understanding the efficacies and toxicities of combination drugs and herbal medicines. Metabolomics has clearly demonstrated its value in elucidating the interaction of the biological system's genome with its environments, and recently been used in the PK analysis of drugs, xenobiotics and several nutrients. The metabolomics strategy can also be used in pharmacokinetic study of plant derived agents to demonstrate their biological fates, thereby linking the plant metabolome to human/animal metabolome, and bridging the gap between multi-component agents and molecular pharmacology. This paper reviews the current progress of metabolomics based PK studies, presents the potentials and challenges of such a strategy for herbal medicines, as well as looks into the future of the role of metabolomics in the relationship between PK, PD and TOX of herbal medicines. PMID- 20302569 TI - Pharmacogenetics of target genes across doxorubicin disposition pathway: a review. AB - Increased understanding of the molecular mechanisms of tumor heterogeneity combined with rapid advances in the field of pharmacogenetics and pharmacogenomics have fuelled studies on individualizing anticancer therapy. Doxorubicin (Adriamycin), is an anthracycline glycoside antibiotic originally produced by Streptomyces peucetius var. caesius, and is widely used either as a single agent or in combination with other chemotherapeutic regimens for curative, adjuvant, and palliative treatment in cancer patients. The pharmacogenetics of doxorubicin has not been well characterized. The polygenic influence of functional candidate gene variants across doxorubicin biochemical pathway is hypothesized to contribute to its heterogeneity in disposition, influencing the efficacy of treatment and occurrence of adverse effects like cardiomyopathy in patients undergoing doxorubicin based adjuvant and neo-adjuvant chemotherapy. The pharmacogenetics of Asian population differs from that of other ethnic groups, particularly from Caucasian and African populations, and indicates an important role of ethnicity in determining predictive end points during chemotherapy and in individualizing treatment. This review comprehensively examines the pharmacogenetics of the regulatory nuclear receptor Pregnane-X Receptor (PXR), influx (SLC22A16) and efflux drug transporters (ABCB1, ABCG2, ABCC5, ABCB5 and RLIP76) and drug metabolizing enzymes (CBR1, CBR3) across the biochemical pathway of doxorubicin in Asian breast cancer patients receiving doxorubicin based adjuvant chemotherapy. The influence of functional genetic variants on the inter individual variability in pharmacokinetics of doxorubicin and its major metabolite are also discussed. The incorporation of non-genetic factors and subsequent validation of these findings in different patient and population groups will be valuable in tailoring doxorubicin dosage regimens to an individual to maximize therapeutic efficacy and minimize adverse reactions, leading to improved clinical outcomes. PMID- 20302570 TI - Iron-binding activity of human iron-sulfur cluster assembly protein hIscA1. AB - A human homologue of the iron-sulfur cluster assembly protein IscA (hIscA1) has been cloned and expressed in Escherichia coli cells. The UV-visible absorption and EPR (electron paramagnetic resonance) measurements reveal that hIscA1 purified from E. coli cells contains a mononuclear iron centre and that the iron binding in hIscA1 expressed in E. coli cells can be further modulated by the iron content in the cell growth medium. Additional studies show that purified hIscA1 binds iron with an iron association constant of approx. 2x1019 M-1, and that the iron-bound hIscA1 is able to provide the iron for the iron-sulfur cluster assembly in a proposed scaffold protein, IscU of E. coli, in vitro. The complementation experiments indicate that hIscA1 can partially substitute for IscA in restoring the cell growth of E. coli in the M9 minimal medium under aerobic conditions. The results suggest that hIscA1, like E. coli IscA, is an iron-binding protein that may act as an iron chaperone for biogenesis of iron sulfur clusters. PMID- 20302571 TI - Langerhans cell histiocytosis: a case study suggesting a reactive aetiology. PMID- 20302566 TI - Update information on drug metabolism systems--2009, part II: summary of information on the effects of diseases and environmental factors on human cytochrome P450 (CYP) enzymes and transporters. AB - The present paper is an update of the data on the effects of diseases and environmental factors on the expression and/or activity of human cytochrome P450 (CYP) enzymes and transporters. The data are presented in tabular form (Tables 1 and 2) and are a continuation of previously published summaries on the effects of drugs and other chemicals on CYP enzymes (Rendic, S.; Di Carlo, F. Drug Metab. Rev., 1997, 29(1-2), 413-580., Rendic, S. Drug Metab. Rev., 2002, 34(1-2), 83 448.). The collected information presented here is as stated by the cited author(s), and in cases when several references are cited the latest published information is included. Inconsistent results and conclusions obtained by different authors are highlighted, followed by discussion of the major findings. The searchable database is available as an Excel file, for information about file availability contact the corresponding author. PMID- 20302572 TI - Frequency of aquagenic palmoplantar keratoderma in cystic fibrosis: a new sign of cystic fibrosis? AB - BACKGROUND: Aquagenic palmoplantar keratoderma (APPK), also known as aquagenic wrinkling of the palms, is characterized by oedema of palms and/or soles, whitish papules, hyperwrinkling and sometimes pruritus or pain after water immersion. Its frequency in the general population is unknown. About 40 cases have been reported to date, including some among patients with cystic fibrosis (CF) or CF heterozygotes. OBJECTIVES: To determine the frequency of APPK among patients with CF. METHODS: Twenty-seven patients from the Centre of Competence on Cystic Fibrosis of Roscoff were examined by a dermatologist after immersion of the palms in water for 2-3 min. RESULTS: The frequency of APPK was 41% (11 of 27 patients). Some patients had not previously noticed the lesions. The frequency was higher among inpatients than outpatients. We suspect that occlusion (caused by the gloves worn by inpatients) can explain this difference. The number of patients included in this study is not sufficient to draw any conclusions concerning the type of CF mutation and its impact on the frequency of APPK. CONCLUSIONS: APPK is frequent among patients with CF and, thus, should be considered a sign of CF. APPK is underdiagnosed because physicians usually do not look for it. CF screening should be considered for any patient presenting with these symptoms, followed by genetic counselling if necessary. PMID- 20302573 TI - Targeted phototherapy of plaque-type psoriasis using ultraviolet B-light-emitting diodes. AB - BACKGROUND: One of the major technological breakthroughs in the last decade is represented by the diversified medical applications of light-emitting diodes (LEDs). LEDs emitting in the ultraviolet (UV) B spectrum might serve as a more convenient alternative for targeted delivery of phototherapy in inflammatory skin diseases such as psoriasis. OBJECTIVES: We investigated the efficacy and safety of a new UVB-LED phototherapeutic device in chronic plaque-type psoriasis. METHODS: Twenty patients with stable plaque-type psoriasis were enrolled into a prospective, right-left comparative, open study. Symmetrical lesions located on extremities or trunk were chosen; one lesion was treated with the study device, whereas the other lesion served as an untreated control. Two treatment regimens were used in the study, one with an aggressive dose escalation similar to those used for outpatient treatment and one with slow increase in dose, similar to those used for treatment at home. RESULTS: Patients in both groups responded rapidly to the UVB-LED therapy. Early disease resolution was observed in 11 patients (seven in the first group and four in the second group). Overall improvement at end of therapy was 93% in the high-dose group and 84% in the low dose group. Four patients from the high-dose group and five from the low-dose group were still in remission at the 6-month follow-up visit. CONCLUSIONS: These results suggest that this innovative UVB-LED device is effective in the treatment of localized psoriasis and may be useful in other UV-responsive skin diseases. PMID- 20302575 TI - The effect of visible light and near-infrared radiation on constitutive pigment of patients with vitiligo. PMID- 20302576 TI - Thyrotropin-releasing hormone and oestrogen differentially regulate prolactin and prolactin receptor expression in female human skin and hair follicles in vitro. AB - BACKGROUND: Human skin and scalp hair follicles are both a nonclassical target and an extrapituitary source of prolactin (PRL), which is a potent hair growth modulator. However, how the expression of PRL and PRL receptor (PRLR) is regulated in human skin is unknown. OBJECTIVES: To investigate whether two key stimulators of pituitary PRL secretion, thyrotropin-releasing hormone (TRH) and oestrogen, also regulate cutaneous PRL and PRLR expression. METHODS: Female scalp skin and/or microdissected hair follicles were treated for 6 days in serum-free organ culture with oestrogen (100 nmol L(-1)), TRH (1-10 ng mL(-1), 3-30 nm) or vehicle control. Quantitative immunohistomorphometry of skin and hair follicle sections was complemented with quantitative polymerase chain reaction for PRL and PRLR in cultured hair follicles and/or female human outer root sheath (ORS) keratinocytes. RESULTS: Oestrogen treatment significantly upregulated PRL and PRLR immunoreactivity in selected skin and hair follicle compartments, at the gene and protein level (P < 0.05). TRH significantly increased PRL immunoreactivity and transcription in hair follicles (P < 0.05); however, while it also increased PRLR transcription in hair follicles, it downregulated PRLR immunoreactivity in the hair follicle ORS (P < 0.05). CONCLUSIONS: Our pilot study shows that two key endocrine controls of pituitary PRL secretion, oestrogen and TRH, also regulate PRL and PRLR expression in human skin. This provides novel insights into the regulation of extrapituitary PRL and PRLR expression, and invites exploration of oestrogen and TRH as novel therapeutic agents in the management of skin and hair diseases characterized by aberrant PRLR-mediated signalling. PMID- 20302577 TI - No clinical benefit of preoperative fluorescence diagnosis of basal cell carcinoma localized in the H-zone of the face. AB - BACKGROUND: Basal cell carcinoma (BCC) is the most common malignant skin carcinoma. Fluorescence diagnosis (FD) has been suggested as a promising method for noninvasive detection of subclinical tumour cell dissemination in BCC. OBJECTIVES: In this prospective study, we evaluated the clinical performance of a preoperative definition of the lateral borders of BCC by FD in comparison with its definition by purely clinical diagnosis (CD). The fluorescence intensity on the skin was recorded using a digital light-emitting diode-based fluorescence imaging system. METHODS: Twenty-six patients with BCC (22 with nodular subtype) of the H-zone were included. The tumour area was determined 3 h after application of methyl aminolaevulinate by inspection and photographic documentation (CD) and FD. Subsequently, BCCs were excised according to the complete area defined by CD and FD with a security margin of 3 mm; surgical specimens were sectioned horizontally and subjected to meticulous histological mapping. The tumour areas as determined by FD, CD and histology were superimposed to map the entire lateral tumour margin. RESULTS: The tumour area could be visualized by FD in 24 of 26 patients. The mean tumour area as determined by FD was significantly smaller than the tumour area as determined by CD [80 mm(2) , 95% confidence interval (CI) 50 110 mm(2) vs. 101 mm(2) , 95% CI 76-125 mm(2) ; P < 0.012]. The superimposition of FD and histology showed in 10 of 26 patients a complete detection of the tumour margin by FD; thus sensitivity of FD was calculated as 38.5%. In only three of 26 patients FD revealed a tumour extent greater than determined by CD. Specificity of FD was calculated as 88.4%. CONCLUSIONS: On aggregate, this study suggests that preoperative FD of nodular BCC localized in the H-zone offers no additional benefit to define subclinical tumour infiltration compared with CD alone. PMID- 20302578 TI - Lethal acantholytic epidermolysis bullosa due to a novel homozygous deletion in DSP: expanding the phenotype and implications for desmoplakin function in skin and heart. AB - Desmoplakin is the major linker in desmosomes in epithelia and myocardium, anchoring intermediate filaments by the C-terminus to plakoglobin and plakophilin in the desmosomal plaque. Mutations in the gene DSP encoding desmoplakin have been associated with various phenotypes affecting skin and/or heart. One of these phenotypes, lethal acantholytic epidermolysis bullosa (LAEB), is characterized by extensive postnatal shedding of epidermis leading to early demise and is caused by recessive mutations in the gene DSP resulting in truncation of the desmoplakin C-terminus. Here we describe two infants born to the same consanguinous parents who suffered extensive epidermal dislodgment and died shortly after birth. In addition, universal alopecia, anonychia, malformed ears and cardiomyopathy were observed. As the clinical diagnosis was LAEB, DSP mutation analysis was performed. A homozygous deletion (c.2874del5) abrogating the donor splice site of exon 20 was found. The deletion is predicted to cause read-through in intron 20 with subsequent recognition of a premature termination codon, resulting in desmoplakin lacking its rod domain and C-terminus (p.Lys959MetfsX5). Electron microscopic analysis of skin biopsies showed absence of the desmosomal inner dense plaque and lack of tonofilament insertion. This is the second report of LAEB. These findings suggest DSP mutations as the aetiology of LAEB and cardiomyopathy as part of the phenotype. Furthermore, they indicate that in addition to the desmoplakin C-terminus, the rod domain is dispensable for intrauterine development but is essential for the inner dense plaque of desmosomes. PMID- 20302579 TI - Lethal autosomal recessive epidermolytic ichthyosis due to a novel donor splice site mutation in KRT10. AB - Epidermolytic ichthyosis (EI; MIM 113800), previously named bullous congenital ichthyosiform erythroderma or epidermolytic hyperkeratosis, is a rare and clinically variable defect of cornification characterized by generalized erythema, erosions, scaling and easily breaking blisters that become less frequent later in life while hyperkeratosis increases. EI is caused by dominant mutations in either KRT1 or KRT10, encoding keratin 1 (K1) and keratin 10 (K10), respectively. Usually, mutations are missense substitutions into the highly conserved alpha-helical rod domains of the proteins. However, three inbred pedigrees in which EI is transmitted as a recessive trait due to KRT10 null mutations have been described. PMID- 20302580 TI - Topical calcitriol restores the impairment of epidermal permeability and antimicrobial barriers induced by corticosteroids. AB - BACKGROUND: The active form of vitamin D(3) , calcitriol, is widely used for the treatment of psoriasis, with or without topical corticosteroids. Topical corticosteroids are known to disrupt permeability and antimicrobial barriers, even with short-term use. Yet, the effect of topical calcitriol on epidermal permeability and antimicrobial barriers disrupted by topical corticosteroids has not been determined. OBJECTIVES: To examine the effect of calcitriol on epidermal permeability and antimicrobial barrier function that has been impaired by corticosteroids, as well as to elucidate the mechanism of improvement. MATERIAL AND METHODS: Topical calcitriol or the control vehicle was applied to each flank of hairless mice 20 min after treatment with topical clobetasol propionate and repeated every 12 h for 3.5 days. Barrier function assessment, Nile red staining, electron microscopy, immunohistochemistry, Western blotting, and real-time reverse transcriptase-polymerase chain reaction studies were performed 24 h after the last application. RESULTS: Epidermis co-treated with topical calcitriol showed an improvement of stratum corneum integrity and barrier recovery, more intense fluorescence staining with Nile red, and an increase in lamellar body (LB) maturation and density, as well as upregulation of major epidermal lipid synthesis-related enzymes (3-hydroxy-3-methylglutaryl-CoA, serine-palmitoyl transferase and fatty acid synthase), mouse beta-defensin 3, cathelin-related antimicrobial peptide and vitamin D receptor. CONCLUSIONS: We found that topical calcitriol restored both the epidermal permeability and antimicrobial barrier that had been impaired by corticosteroids. This restoration was mediated by both an activation of the cutaneous vitamin D pathway and an increase of epidermal lipids and antimicrobial peptides, promoted by the formation of the LB and the activity of epidermal lipid synthesis-related enzymes. PMID- 20302581 TI - Treatment of so-called idiopathic follicular mucinosis with hydroxychloroquine. AB - There exists no treatment of choice for follicular mucinosis (FM). Historically two distinct entities of FM have been proposed: FM of children and young adults not associated with other diseases ('idiopathic' FM), and FM in elderly patients associated with mycosis fungoides and Sezary syndrome ('lymphoma-associated' FM). Nowadays it is suggested that 'idiopathic' FM might represent a localized form of cutaneous T-cell lymphoma. Six patients with 'idiopathic' FM were treated with hydroxychloroquine (HCQ) at a dose of 200 mg three times daily for 10 days followed by a dose adjusted to the ideal body weight, usually 200 mg twice daily. All patients showed an improvement of 'idiopathic' FM already after 6 weeks and a complete remission with full hair regrowth after 2-5 months of HCQ therapy. In all patients no relapse occurred during follow up of between 3 and 23 years and no patient developed lymphoma. We conclude that HCQ is a highly effective therapy without significant side-effects in the treatment of so-called 'idiopathic' FM. PMID- 20302582 TI - High-concentration (20 MUg g-1 ) tacalcitol ointment in the treatment of facial psoriasis: an 8-week open-label clinical trial. AB - BACKGROUND: Facial psoriasis gives rise to considerable concern because of associated cosmetic problems and psychosocial distress. It requires a treatment approach other than topical corticosteroids, which bear a risk of cutaneous adverse reactions. Recently, topical tacalcitol has been shown to be effective in psoriasis. OBJECTIVES: The aim of this open-label single-centre study is to investigate the efficacy and safety of high-concentration (20 MUg g-1) ) tacalcitol ointment (Bonalfa-high((r)) , Teijin Pharma, Tokyo, Japan) in patients with facial psoriasis and to evaluate clinical response according to the distribution of facial psoriatic lesions. PATIENTS AND METHODS: Thirty-seven patients were enrolled to this clinical trial. Tacalcitol 20 MUg g-1 ointment was applied once daily to psoriatic lesions of the face over an 8-week period. Patients were also categorized into three subtypes according to facial lesion distribution. Efficacy was evaluated by the facial Psoriasis Area and Severity Index (facial PASI) and the Physician's Global Assessment (PGA) score at weeks 2, 4 and 8. The Subjective Global Assessment (SGA) was also determined at the end of the study. RESULTS: Thirty-three patients completed the clinical trial. Mean facial PASI of 33 patients at baseline was 9.58 and after 8 weeks of treatment the mean facial PASI decreased significantly to 3.88. By using PGA, patients showed the following responses to treatment: clearance (n = 1); excellent (6); good (16); fair (4); slight (5); no change (1). The response rate among the three facial psoriasis types showed no difference. Using the SGA, 27 (82%) of the patients presented excellent (15%) or good (67%) effect with tacalcitol 20 MUg g 1 ointment. No serious adverse reactions were observed. CONCLUSIONS: This is the first clinical study reporting a relevant therapeutic effect and favourable safety profile of tacalcitol 20 MUg g-1 ointment in facial psoriasis. These results suggest that tacalcitol 20 MUg g-1 ointment can be used as the first-line treatment in patients with facial psoriasis. PMID- 20302583 TI - Mechanisms of the sensory effects of tacrolimus on the skin. AB - BACKGROUND: Tacrolimus is an immunosuppressant drug currently used for the treatment of atopic dermatitis and pruritus. This topical therapy is effective and safe, but transient burning, stinging and itch are frequently reported. OBJECTIVES: To understand the mechanisms underlying these burning sensations. METHODS: We examined the impact of tacrolimus on substance P (SP) release in an in vitro model of cutaneous neurogenic inflammation. Because phosphorylation of TRPV1 (transient receptor potential subtype vanilloid 1) plays a role in the induction of pain, we investigated whether tacrolimus regulates the phosphorylation state of TRPV1. Finally, we used a macropatch to evaluate the impact of tacrolimus on voltage-gated calcium currents of sensory neurons. RESULTS: Tacrolimus was able to induce initial SP release by extracellular calcium influx and inhibited SP release induced by capsaicin after 1, 24 and 72 h of pretreatment. Analysis of TRPV1 phosphorylation by Western blot confirmed the capacity of tacrolimus to favour phosphorylation. An electrophysiological study showed inhibitory effects on calcium currents. CONCLUSIONS: The efficacy of tacrolimus in pruritus, as well as the sensory side-effects, could be explained by a direct effect on neurons through an effect on calcineurin, possibly by a desensitization of TRPV1 and calcium currents through the PIP(2) regulation pathway. PMID- 20302585 TI - Guidelines for the management of Helicobacter pylori infection in Japan: 2009 revised edition. AB - BACKGROUND: Over the past few years, the profile of Helicobacter pylori infection has changed in Japan. In particular, the relationship between H. pylori and gastric cancer has been demonstrated more clearly. Accordingly, the committee of the Japanese Society for Helicobacter Research has revised the guidelines for diagnosis and treatment of H. pylori infection in Japan. MATERIALS AND METHODS: Four meetings of guidelines preparation committee were held from July 2007 to December 2008. In the new guidelines, recommendations for treatment have been classified into five grades according to the Minds Recommendation Grades, while the level of evidence has been classified into six grades. The Japanese national health insurance system was not taken into consideration when preparing these guidelines. RESULTS: Helicobacter pylori eradication therapy achieved a Grade A recommendation, being useful for the treatment of gastric or duodenal ulcer, for the treatment and prevention of H. pylori-associated diseases such as gastric cancer, and for inhibiting the spread of H. pylori infection. Levels of evidence were determined for each disease associated with H. pylori infection. For the diagnosis of H. pylori infection, measurement of H. pylori antigen in the feces was added to the tests not requiring biopsy. One week of proton-pump inhibitor based triple therapy (including amoxicillin and metronidazole) was recommended as second-line therapy after failure of first-line eradication therapy. CONCLUSION: The revised Japanese guidelines for H. pylori are based on scientific evidence and avoid the administrative restraints that applied to earlier versions. PMID- 20302584 TI - Immunosuppressive effect of prolactin-induced protein: a new insight into its local and systemic role in chronic allergic contact dermatitis. AB - BACKGROUND: Prolactin-induced protein (PIP) has been shown to bind to CD4 and is speculated to block CD4-HLA-DR interaction. However, the immunomodulatory effect of PIP on chronic allergic contact dermatitis (ACD) remains to be elucidated. OBJECTIVES: To define the role of PIP during the immunoresponse. METHODS: Using a low-dose oxazolone-induced mouse chronic ACD model, expression of PIP was examined immunohistologically. Furthermore, effects of continued exposure to a peptide mimicking the major binding site of PIP (amino acids 106-132) for CD4 was examined in a mouse chronic ACD model. RESULTS: We clarified that keratinocytes, dermal infiltrating cells and spleen infiltrating mononuclear cells are positively stained with anti-PIP antibody. The PIP peptide significantly downregulated oxazolone-induced mouse ACD compared with controls. We also found that inflammation of the control ear, to which the PIP peptide had not been applied, was also suppressed in a synchronized manner in the late phase of ACD. CONCLUSIONS: These findings suggest that PIP might have a local and systemic immunosuppressive effect in mouse chronic ACD. PMID- 20302586 TI - High level of antimicrobial resistance in French Helicobacter pylori isolates. AB - BACKGROUND: Helicobacter pylori is a human pathogen responsible for serious diseases including peptic ulcer disease and gastric cancer. The recommended triple therapy included clarithromycin but increasing resistance has undermined its effectiveness. It is therefore important to be aware of the local prevalence of antimicrobial resistance to adjust treatment strategy. MATERIALS AND METHODS: Overall, 530 biopsies were collected between 2004 and 2007. The antimicrobial susceptibility of H. pylori was determined by E-test and molecular methods. RESULTS: Among these, 138/530 (26%) strains were resistant to clarithromycin, 324/530 (61%) to metronidazole and 70/530 (13.2%) to ciprofloxacin. Whereas no resistance against amoxicillin and tetracycline was observed, only one strain was resistant to rifampicin. Compared to the patients never treated for H. pylori infection, the prevalence of resistance was significantly higher in patients previously treated (19.1% vs 68% for clarithromycin; 13.2% vs 53.3% for both clarithromycin and metronidazole). The trend analysis revealed an increase of primary resistance to ciprofloxacin between 2004 and 2005 (7.3%) vs 2006-2007 (14.1%) (p = .04) and the secondary resistance reached 22.7% in 2007. Interestingly, 27 biopsies (19.6%) contained a double population of clarithromycin-susceptible and -resistant strains. CONCLUSIONS: The reported high prevalence of clarithromycin and multiple resistances of H. pylori suggest that the empiric therapy with clarithromycin should be abandoned as no longer pretreatment susceptibility testing has assessed the susceptibility of the strain. As culture and antibiogram are not routinely performable in most clinical laboratories, the use of molecular test should be developed to allow a wide availability of pretreatment susceptibility testing. PMID- 20302587 TI - A "screen-and-treat" approach for Helicobacter pylori infection: a population based study in Vammala, Finland. AB - BACKGROUND: To accelerate the decline of Helicobacter pylori infection, and to study the significance of the possible risk factors for H. pylori infection in Finland, we started a voluntary H. pylori"screen-treat-retest-and-retreat" program for all young adults at primary health care in Vammala, Finland after a pilot study in 1994 including 504 subjects aged 15-75. MATERIALS AND METHODS: A total of 3326 aged 15-40 in 1996, and 716 aged 15 and 584 aged 45 in 1997-2000 were screened for H. pylori using serology. Helicobacter pylori positive were treated, cure was verified by serology. RESULTS: The eradication rates were 93.8%, 82.2%, and 77.6% per protocol in pilot study in 1994, in subjects invited in 1996 and 1997-2000, respectively. Helicobacter pylori seroprevalence rates were calculated to have decreased from 36% to 14% in pilot study, from 12% to 4% among subjects invited in 1996, from 3% to 2% among subjects aged 15 and from 27% to 12% among subjects aged 45 in 1997-2000. An epidemiologic questionnaire in 1996 revealed that crowding in the childhood household, low education of the mother, current smoking and alcohol consumption, unfavorable housing conditions, and sick leaves due to dyspepsia were independently associated with H. pylori infection. CONCLUSIONS: This intervention with high participation rates resulted in a significant decline in calculated H. pylori seroprevalence rates. Although the low prevalence of H. pylori infection may limit the cost efficiency of the program, the intervention is expected to reduce the burden of H. pylori associated diseases. PMID- 20302588 TI - Bismuth-containing quadruple therapy as second-line treatment for Helicobacter pylori infection: effect of treatment duration and antibiotic resistance on the eradication rate in Korea. AB - BACKGROUND: The eradication rate of first-line Helicobacter pylori treatment is only 70-85% and has been decreasing due to the increase in antibiotic resistance. The aim of this study was to evaluate the efficacy of bismuth-containing quadruple therapy as second-line treatment for H. pylori infection based on treatment duration. METHODS: We prospectively enrolled 227 patients that were found to have persistent H. pylori infection after first-line proton-pump inhibitor-clarithromycin-amoxicillin triple therapy. Patients were randomized to 1-week (112 patients) and 2-week (115 patients) quadruple therapy with tripotassium dicitrate bismuthate 300 mg q.i.d., metronidazole 500 mg t.i.d., and tetracycline 500 mg q.i.d. and esomeprazole 20 mg b.i.d. The eradication rate, drug compliance, and adverse events were compared based on treatment duration. RESULTS: The eradication rates were 72/112 (64.3%, 95% CI: 0.504-0.830) and 71/92 (77.2%, 0.440-0.749) with 1-week group, and 95/115 (82.6%, 1.165-2.449) an 88/94 (93.6%, 1.213-5.113) with 2-week group by intention-to-treat therapy (p = .002) and per-protocol analysis (p = .001), respectively. The adverse events increased as the treatment durations increased from 7 to 14 days (20.0 and 42.5%, respectively, p < .001). However, there was no significant difference in the patient compliance or the rate of major adverse events between the 1- and 2-week groups (6.3 and 12.5%, respectively, p = .133). CONCLUSION: Two-week bismuth containing quadruple therapy was more effective than the 1-week treatment, and should be considered for second-line treatment in Korea. PMID- 20302589 TI - Helicobacter pylori reinfection in Brazilian patients with peptic ulcer disease: a 5-year follow-up. AB - BACKGROUND: The Helicobacter pylori reinfection seems to be higher in developing countries, than in developed ones. The aim of the study was to determine the annual recurrence rate of H. pylori, in Brazilian patients with peptic ulcer disease, in a 5-year follow-up. METHODS: Patients, with peptic ulcer disease diagnosed by upper digestive endoscopy (UDE) and H. pylori infection verified by histological analysis, rapid urease test, polymerase chain reaction, and urea breath test (UBT), were treated for bacterial eradication. The cure of the infection was verified using the same tests, 3 months after. Clinical evaluation and UBT were performed after sixth and ninth month. After 1 year of follow-up, UBT and UDE were repeated. Up to the fifth year, patients were assessed twice a year and an UBT was performed annually. The patients included and all the reinfected were tested for 15 different genes of the H. pylori. RESULTS: One hundred and forty-seven patients were followed: 19 for 1 year, eight for 2 years, four for 3 years, five for 4 years, and 98 for 5 years, totaling 557 patients/years. Recurrence did not occur in the first year. In the second year, two patients were reinfected; in the third, four patients; in the fourth, three patients; and in the fifth, one patient. The total of reinfected patients was 10. The annual reinfection rate was 1.8%. CONCLUSION: Brazil presents a low prevalence of H. pylori reinfection, similar to the developed countries. PMID- 20302590 TI - Helicobacter pylori cagA gene polymorphism affects the total antioxidant capacity of human saliva. AB - BACKGROUND: We aimed to evaluate the total antioxidant capacity (TAC) of saliva in healthy Helicobacter pylori-positive and negative saliva individuals. MATERIALS AND METHODS: A total of 102 human saliva samples were checked for the presence of H. pylori DNA (ureA and cagA gene fragments). TAC of saliva was estimated by ABTS radical cation (ABTS( +)) decolorization assay. RESULTS: PCR analysis revealed that 36 subjects were ureA-/cagA-, 24 were ureA+/cagA- and 42 were ureA+/cagA+. Smoking habits had no evident effect on H. pylori infection. We found that TAC of the ureA-/cagA- material, after 10 seconds reaction reflecting fast-reacting antioxidants, was significantly higher than of ureA+/cagA- and ureA+/cagA+ samples (p < .01 and p < .001, respectively). Similar results were obtained for reaction time of 3 minutes measuring slow-reacting antioxidants (p < .001). We also estimated ureA+/cagA- and ureA+/cagA+ samples alone and reported a statistically significant decrease in the TAC(3 min) value of ureA+/cagA+ compared with ureA+/cagA- samples (p < .05). CONCLUSIONS: Our data demonstrated that altered redox equilibrium may be associated with more frequent occurrence of H. pylori in the saliva samples. PMID- 20302591 TI - Characterization of multiple Helicobacter bizzozeronii isolates from a Finnish patient with severe dyspeptic symptoms and chronic active gastritis. AB - BACKGROUND: Helicobacter pylori is the primary cause of gastritis and peptic ulceration in humans. In a minority of patients with upper gastrointestinal symptoms, long tightly coiled spiral bacteria, provisionally named "Helicobacter heilmannii," are observed in gastric biopsies. These bacteria are extremely fastidious and only one previous study has succeeded in obtaining an isolate in vitro. MATERIALS AND METHODS: We used two different selective media to isolate "H. heilmannii" from the gastric mucosa of a Finnish patient presenting with severe dyspeptic symptoms. The isolates were characterized by testing for urease and catalase activity, by using light and electron microscopy, and by sequencing of the partial 16S rRNA and ureAB genes. Single-enzyme amplified fragment length polymorphism (sAFLP) was used to analyze the genetic diversity among the isolates. RESULTS: We obtained 15 isolates from different gastric biopsies prior and three after unsuccessful treatment of the patient. The isolates were identified as Helicobacter bizzozeronii. Eradication therapy was unsuccessful most probably due to high level of resistance to metronidazole. Persistent colonization by the same H. bizzozeronii clone was confirmed by sAFLP, however, small differences between the profiles suggested long-term colonization of the patient. CONCLUSIONS: Helicobacter bizzozeronii remains the only "H. heilmannii" species isolated from human gastric mucosa although it has been an infrequent observation among "H. heilmannii"-infected patients in PCR-based screening studies. The relevance of H. bizzozeronii and other potentially zoonotic gastric Helicobacter spp. in human disease remains to be determined. PMID- 20302592 TI - Gastric Infection with Kazachstania heterogenica influences the outcome of a Helicobacter suis infection in Mongolian gerbils. AB - BACKGROUND: The Mongolian gerbil model is often used to investigate the interactions between different gastric Helicobacter species and the gastric tissue. A preliminary screening of a gerbil population intended for use in Helicobacter suis infection studies revealed a natural yeast infection in the stomach of these animals. After identification, we have investigated the effect of the gastric yeast infection on the outcome of an experimental H. suis infection in Mongolian gerbils. MATERIALS AND METHODS: Yeast cells were isolated from the stomachs of Mongolian gerbils. Identification was done by Internally Transcribed rRNA Spacer 2 Region PCR fragment length analysis. To investigate a possible pathologic role of this yeast, Mongolian gerbils were infected experimentally with this yeast. Co-infection with the newly isolated H. suis was performed to investigate possible interactions between both micro-organisms. RESULTS: Kazachstania heterogenica was found colonizing the stomach of Mongolian gerbils, mainly in the antrum. Few pathologic changes were seen in the stomachs of infected animals. Experimental co-infection of gerbils with this yeast and the newly isolated H. suis showed a significant increase in inflammation in animals infected with both micro-organisms compared to animals infected only with H. suis. CONCLUSIONS: K. heterogenica colonizes the stomach of Mongolian gerbils in exactly the same regions as gastric Helicobacter species. The uncontrolled presence of this yeast in the gerbil stomach can lead to an overestimation of the inflammation caused by Helicobacter in this animal model. PMID- 20302593 TI - Molecular alterations in fibroblasts exposed to Helicobacter pylori broth culture filtrate: a potential trigger of autoimmunity? PMID- 20302595 TI - Splenectomy improves survival by increasing arterial blood supply in a rat model of reduced-size liver. AB - Prevention of acute portal hyperperfusion in small-for-size livers by inflow modulation results in beneficial postoperative outcome. The objective of this study was to unravel the underlying mechanism, emphasizing the intimate relationship between portal venous (PV) and hepatic arterial (HA) blood flow (BF). Rats underwent partial hepatectomy (pHx), splenectomy before pHx or splenectomy and ligation of the A. hepatica before pHx. Portal venous blood flow (PVBF), hepatic arterial blood flow (HABF), and tissue pO2 were assessed during stepwise resection from 30% to 90%. Hepatic regeneration and hypoxia-responsive gene expression were analyzed in each group after nonlethal 85% pHx. 90% pHx caused a fourfold rise in PVBF, a slight decrease in HABF with a 50% reduction in pO2, and high mortality. Splenectomy before pHx reduced the PVBF and caused a rise in HABF with doubling in tissue pO2. An attenuation of hypoxia-responsive gene expression turned into enhanced hepatocellular regeneration and improved survival. A. hepatica ligation abolished the beneficial effect of splenectomy on tissue oxygenation, proliferation, and outcome. In conclusion, the beneficial effect of splenectomy in small-for-size livers can be attributed to a rise in HABF with sufficient oxygen supply rather than to a reduced portal venous hyperperfusion to the remnant liver. PMID- 20302596 TI - Comparison between VDR analogs and current immunosuppressive drugs in relation to CXCL10 secretion by human renal tubular cells. AB - During kidney allograft rejection, CXC chemokine ligand 10 (CXCL10)-CXC chemokine receptor 3 (CXCR3) trafficking between peripheral blood and tissues initiates alloresponse and perpetuates a self-inflammatory loop; thus, CXCL10-CXCR3 axis could represent a pharmacologic target. In this perspective, immunosuppressors targeting graft-resident cells, beside immune cells, could be very advantageous. Vitamin D receptor (VDR) agonists exhibit considerable immunomodulatory properties. This study aimed to investigate whether elocalcitol and BXL-01-0029 could decrease the expression of CXCL10 in activated renal tubular cells in vitro and thus be useful in kidney allograft rejection treatment. Experiments were performed in human tubular renal cells stimulated with interferon-gamma + tumor necrosis factor-alpha with and without VDR agonists, tacrolimus, sirolimus, hydrocortisone, methylprednisolone, cyclosporin A and mycophenolate mofetil. CXCL10 protein secretion and gene expression were measured by ELISA and by quantitative PCR. Specific inhibitors were used to investigate intracellular pathways involved in tubular cells activation. For IC(50) determination and comparison, dose-response curves with VDR agonists, tacrolimus and mycophenolic acid were performed. Elocalcitol and BXL-01-0029 inhibited CXCL10 secretion by renal cells, without affecting cell viability, while almost all the immunosuppressors were found to be ineffective, except for tacrolimus and mycophenolate mofetil. BXL-01-0029 was the most potent drug and, notably, it was found to be capable of allowing reduction in tacrolimus-inhibitory doses. Our data suggest that BXL-01-0029 could potentially be a dose-reducing agent for conventional immunosuppressors in kidney rejection management. PMID- 20302597 TI - A method for release and multiple strand amplification of small quantities of DNA from endospores of the fastidious bacterium Pasteuria penetrans. AB - AIMS: To establish a reliable protocol to extract DNA from Pasteuria penetrans endospores for use as template in multiple strand amplification, thus providing sufficient material for genetic analyses. To develop a highly sensitive PCR-based diagnostic tool for P. penetrans. METHODS AND RESULTS: An optimized method to decontaminate endospores, release and purify DNA enabled multiple strand amplification. DNA purity was assessed by cloning and sequencing gyrB and 16S rRNA gene fragments obtained from PCR using generic primers. Samples indicated to be 100%P. penetrans by the gyrB assay were estimated at 46% using the 16S rRNA gene. No bias was detected on cloning and sequencing 12 housekeeping and sporulation gene fragments from amplified DNA. The detection limit by PCR with Pasteuria-specific 16S rRNA gene primers following multiple strand amplification of DNA extracted using the method was a single endospore. CONCLUSIONS: Generation of large quantities DNA will facilitate genomic sequencing of P. penetrans. Apparent differences in sample purity are explained by variations in 16S rRNA gene copy number in Eubacteria leading to exaggerated estimations of sample contamination. Detection of single endospores will facilitate investigations of P. penetrans molecular ecology. SIGNIFICANCE AND IMPACT OF THE STUDY: These methods will advance studies on P. penetrans and facilitate research on other obligate and fastidious micro-organisms where it is currently impractical to obtain DNA in sufficient quantity and quality. PMID- 20302598 TI - Mechanism of killing of spores of Bacillus cereus and Bacillus megaterium by wet heat. AB - AIMS: To determine the mechanism of wet heat killing of spores of Bacillus cereus and Bacillus megaterium. METHODS AND RESULTS: Bacillus cereus and B. megaterium spores wet heat-killed 82-99% gave two bands on equilibrium density gradient centrifugation. The lighter band was absent from spores that were not heat treated and increased in intensity upon increased heating times. These spores lacked dipicolinic acid (DPA) were not viable, germinated minimally and had much denatured protein. The spores in the denser band had viabilities as low as 2% of starting spores but retained normal DPA levels and most germinated, albeit slowly. However, these largely dead spores outgrew poorly if at all and synthesized little or no ATP following germination. CONCLUSIONS: Wet heat treatment appears to kill spores of B. cereus and B. megaterium by denaturing one or more key proteins, as has been suggested for wet heat killing of Bacillus subtilis spores. SIGNIFICANCE AND IMPACT OF THE STUDY: This work provides further information on the mechanisms of killing of spores of Bacillus species by wet heat, the most common method for spore inactivation. PMID- 20302599 TI - Inhibition of Orientia tsutsugamushi infection by a truncated recombinant 56-kDa outer membrane protein. AB - AIMS: The objective of this study was to evaluate recombinant 56-kDa outer membrane protein as a potential inhibitor to infection from Orientia tsutsugamushi. METHODS AND RESULTS: The 56-kDa protein was cloned and expressed in an Escherichia coli system, and the degree of target cell attachment to immobilized 56-kDa protein was measured in a cell adhesion assay. The results showed that the 56-kDa protein has an ability to attach HeLa cells. Furthermore, treatment of target cells with a truncated 56-kDa 1-418 (amino acid residues) protein inhibited target cell infection by O. tsutsugamushi, demonstrated with an indirect immunofluorescence antibody assay. CONCLUSIONS: The truncated 56-kDa protein (a.a. 1-418) plays an important role in O. tsutsugamushi infection, and the 56-kDa protein could be useful and effective in the inhibition of O. tsutsugamushi attachment and infection. SIGNIFICANCE AND IMPACT OF THE STUDY: The attachment of the 56-kDa protein to target cells was directly determined by in vitro adherence test, and the invasion of target cells by O. tsutsugamushi was inhibited by treating the target cells with a truncated 56-kDa protein. PMID- 20302600 TI - Differences in Rubisco content and its synthesis in leaves at different positions in Eucalyptus globulus seedlings. AB - The dynamics of ribulose 1.5-bisphosphate carboxylase/oxygenase (Rubisco) content and turnover during leaf development are not well understood in woody plants. Rubisco synthesis, N influx and the mRNA levels of Rubisco-encoding genes were determined as a function of leaf position in 4.5-month-old Eucalyptus globulus seedlings. Rubisco concentration was slightly higher in the top leaves as leaf expansion progressed and was almost maximal in the uppermost fully expanded leaves. Rubisco concentration remained almost constant in the fully expanded leaves at the top and middle positions and then became slightly low at the lowest positions. Rubisco synthesis was active only in the top leaves. These results suggest that Rubisco turnover rate is low in the middle leaves, leading to the maintenance of Rubisco contents, and that Rubisco degradation primarily occurs in the lowest leaves. Changes in the RBCS and rbcL mRNA levels were roughly parallel with Rubisco synthesis, but N influx was more closely correlated with Rubisco synthesis. These results suggest that N influx rather than the transcript abundance of Rubisco-encoding genes is of primary importance in regulating the rate of Rubisco synthesis. Additionally, expression of RBCS multigene family in E. globulus leaves was discussed. PMID- 20302601 TI - Changes in diurnal patterns within the Populus transcriptome and metabolome in response to photoperiod variation. AB - Changes in seasonal photoperiod provides an important environmental signal that affects the timing of winter dormancy in perennial, deciduous, temperate tree species, such as hybrid aspen (Populus tremula x Populus tremuloides). In this species, growth cessation, cold acclimation and dormancy are induced in the autumn by the detection of day-length shortening that occurs at a given critical day length. Important components in the detection of such day-length changes are photoreceptors and the circadian clock, and many plant responses at both the gene regulation and metabolite levels are expected to be diurnal. To directly examine this expectation and study components in these events, here we report transcriptomic and metabolomic responses to a change in photoperiod from long to short days in hybrid aspen. We found about 16% of genes represented on the arrays to be diurnally regulated, as assessed by our pre-defined criteria. Furthermore, several of these genes were involved in circadian-associated processes, including photosynthesis and primary and secondary metabolism. Metabolites affected by the change in photoperiod were mostly involved in carbon metabolism. Taken together, we have thus established a molecular catalog of events that precede a response to winter. PMID- 20302602 TI - Patterns of PIP gene expression in Populus trichocarpa during recovery from xylem embolism suggest a major role for the PIP1 aquaporin subfamily as moderators of refilling process. AB - Embolism and the refilling of xylem vessels are intrinsic to the ability of plants to handle the transport of water under tension. Although the formation of an embolized vessel is an abiotic process, refilling against the pressure gradient requires biological activity to provide both the energy and the water needed to restore xylem transport capacity. Here, we present an analysis of the dynamics of embolism and refilling in Populus trichocarpa and follow temporal dynamics of co-occurring changes in expression level of aquaporins. Under mesic conditions, we found that the percent loss of conductance (PLC) varied diurnally by as much as 20%, suggesting a continuous embolism/refilling cycle. An increase in water stress tilted the balance between the two processes and increased the PLC to as much as 80%. Subsequent re-watering resulted in the reversal of water stress and recovery of PLC to pre-stress levels. Stem parenchyma cells responded to drought stress with considerable up-regulation of the PIP1 subfamily of water channels but not the PIP2 subfamily. Even more significant was the finding that PoptrPIP1.1 and PoptrPIP1.3 genes were up-regulated in response to embolism, but not to water stress, and were down-regulated after embolism removal, suggesting a local ability of plants to sense an embolism presence. PMID- 20302603 TI - Exploring genetic and expression differences between physiologically extreme ecotypes: comparative genomic hybridization and gene expression studies of Kas-1 and Tsu-1 accessions of Arabidopsis thaliana. AB - Recent studies have documented remarkable genetic variation among Arabidopsis thaliana accessions collected from diverse habitats. Of particular interest are accessions with putatively locally adapted phenotypes - that is, accessions with attributes that are likely adaptive at their sites of origin. These genotypes may provide insight into the genetic basis of adaptive evolution as well as allow the discovery of genes of ecological importance. We studied the physiology, genome content and gene expression of two physiologically extreme accessions (Tsu-1 from Tsushima, Japan and Kas-1 from Kashmir, India). Our study was conducted under two levels of soil moisture and accompanied by physiological measurements to characterize early responses to soil drying. Genomic hybridizations identified 42,503 single feature polymorphisms (SFP) between accessions, providing an initial screen for genetic differences. Transcript profiling identified a large number (5996) of genes exhibiting constitutive differences in expression including genes involved in many biological pathways. Mild soil drying resulted in only subtle physiological responses but resulted in gene expression changes in hundreds of transcripts, including 352 genes exhibiting differential responses between accessions. Our results highlight the value of genomic studies of natural accessions as well as identify a number of candidate genes underlying physiological differences between Tsu-1 and Kas-1. PMID- 20302604 TI - Rice leaf growth and water potential are resilient to evaporative demand and soil water deficit once the effects of root system are neutralized. AB - Rice is known to be sensitive to soil water deficit and evaporative demand, with a greatest sensitivity of lowland-adapted genotypes. We have analysed the responses of plant water relations and of leaf elongation rate (LER) to soil water status and evaporative demand in seven rice genotypes belonging to different species, subspecies, either upland- or lowland-adapted. In the considered range of soil water potential (0 to -0.6 MPa), stomatal conductance was controlled in such a way that the daytime leaf water potential was similar in well-watered, droughted or flooded conditions (isohydric behaviour). A low sensitivity of LER to evaporative demand was observed in the same three conditions, with small differences between genotypes and lower sensitivity than in maize. The sensitivity of LER to soil water deficit was similar to that of maize. A tendency towards lower sensitivities was observed in upland than lowland genotypes but with smaller differences than expected. We conclude that leaf water status and leaf elongation of rice are not particularly sensitive to water deficit. The main origin of drought sensitivity in rice may be its poor root system, whose effect was alleviated in the study presented here by growing plants in pots whose soil was entirely colonized by roots of all genotypes. PMID- 20302605 TI - Root herbivores and detritivores shape above-ground multitrophic assemblage through plant-mediated effects. AB - 1. Indirect effects mediated by changes in plant traits are the main mechanism by which above- and below-ground herbivores affect each other and their enemies. Only recently the role of decomposers in the regulation of such plant-based systems has been considered. We hypothesized that: (i) below-ground organisms, both herbivores (negative effect on plants) and detritivores (positive effect on plants), will have a profound effect on the interactions among above-ground arthropods; (ii) floral herbivores will negatively affect other above-ground herbivores associated with the plant; and (iii) not only above- and below-ground herbivores, but also detritivores will affect the production of secondary metabolites, i.e. glucosinolates, in the plants. 2. We manipulated the presence of above-ground herbivores, below-ground herbivores and below-ground detritivores on the Brassicaceae Moricandia moricandioides in the field to disentangle their individual and combined effects on other organism groups. We also investigated their effects on the plant's chemical defence to evaluate potential mechanisms. 3. Our results show that not only above- and below-ground herbivores, but also detritivores affected other herbivores and parasitoids associated with the host plant. Most effects were not additive because their strength changed when other organisms belonging to different functional groups or food web compartments were present. Moreover, below-ground herbivore and detritivore effects on above-ground fauna were related to changes in glucosinolate concentrations and in quantity of resources. 4. This study indicates that multitrophic interactions in plant-based food webs can dramatically change by the action of below-ground organisms. One of the most important and novel results is that detritivores induced changes in plant metabolites, modifying the quality and attractiveness of plants to herbivores and parasitoids under field conditions. PMID- 20302606 TI - Expression, regulation and clinical significance of soluble and membrane CD14 receptors in pediatric inflammatory lung diseases. AB - BACKGROUND: Inflammatory lung diseases are a major morbidity factor in children. Therefore, novel strategies for early detection of inflammatory lung diseases are of high interest. Bacterial lipopolysaccharide (LPS) is recognized via Toll-like receptors and CD14. CD14 exists as a soluble (sCD14) and membrane-associated (mCD14) protein, present on the surface of leukocytes. Previous studies suggest sCD14 as potential marker for inflammatory diseases, but their potential role in pediatric lung diseases remained elusive. Therefore, we examined the expression, regulation and significance of sCD14 and mCD14 in pediatric lung diseases. METHODS: sCD14 levels were quantified in serum and bronchoalveolar lavage fluid (BALF) of children with infective (pneumonia, cystic fibrosis, CF) and non infective (asthma) inflammatory lung diseases and healthy control subjects by ELISA. Membrane CD14 expression levels on monocytes in peripheral blood and on alveolar macrophages in BALF were quantified by flow cytometry. In vitro studies were performed to investigate which factors regulate sCD14 release and mCD14 expression. RESULTS: sCD14 serum levels were specifically increased in serum of children with pneumonia compared to CF, asthma and control subjects. In vitro, CpG induced the release of sCD14 levels in a protease-independent manner, whereas LPS-mediated mCD14 shedding was prevented by serine protease inhibition. CONCLUSIONS: This study demonstrates for the first time the expression, regulation and clinical significance of soluble and membrane CD14 receptors in pediatric inflammatory lung diseases and suggests sCD14 as potential marker for pneumonia in children. PMID- 20302608 TI - Control of disseminated intravascular coagulation in Klippel-Trenaunay-Weber syndrome using enoxaparin and recombinant activated factor VIIa: a case report. AB - INTRODUCTION: Vascular malformation is associated with coagulopathies, especially when hemostasis is challenged. CASE PRESENTATION: We present the case of an 11 year-old Hispanic girl with Klippel-Trenaunay-Weber syndrome that developed disseminated intravascular coagulation after minor surgery, which was controlled by blood product transfusions and enoxaparin to address an ongoing consumptive coagulopathy. The patient, however, developed bacteremia and liver trauma that resulted in severe bleeding. To the best of our knowledge, we report here the first known instance of administering recombinant coagulation factor VIIa to control acute bleeding in a patient with Klippel-Trenaunay-Weber syndrome. CONCLUSIONS: This case illustrates the concept of enoxaparin maintenance to suppress an ongoing consumptive coagulopathy and the use of recombinant coagulation factor VIIa to control its potentially fatal severe bleeding episodes. PMID- 20302607 TI - Cortico-cerebral histogenesis in the opossum Monodelphis domestica: generation of a hexalaminar neocortex in the absence of a basal proliferative compartment. AB - BACKGROUND: The metatherian Monodelphis domestica, commonly known as the South American short-tailed opossum, is an appealing animal model for developmental studies on cortico-cerebral development. Given its phylogenetic position, it can help in tracing evolutionary origins of key traits peculiar to the eutherian central nervous system. The capability of its pup to regenerate damaged cortico spinal connections makes it an ideal substrate for regenerative studies. Recent sequencing of its genome and the ex utero accessibility of its developing cerebral cortex further enhance its experimental interest. However, at the moment, a comprehensive cellular and molecular characterization of its cortical development is missing. RESULTS: A systematic analysis of opossum cortico cerebral development was performed, including: origin of cortical neurons; migration of these neurons from their birthplaces to their final layer destinations; and molecular differentiation of distinct neocortical laminae. We observed that opossum projection neurons and interneurons are generated by pallial and subpallial precursors, respectively, similar to rodents. A six layered cortex with a eutherian-like molecular profile is laid down, according to the inside-out rule. However, neocortical projection neurons are generated by apical neural precursors and almost no basal progenitors may be found in the neuronogenic neopallial primordium. In the opossum neocortex, Tbr2, the hallmark of eutherian basal progenitors, is transiently expressed by postmitotic progenies of apical precursors prior to the activation of more mature neuronal markers. CONCLUSIONS: The neocortical developmental program predates Eutheria-Methatheria branching. However, in metatherians, unlike eutherians, a basal proliferative compartment is not needed for the formation of a six-layered neuronal blueprint. PMID- 20302609 TI - Acute mercury poisoning: a case report. AB - BACKGROUND: Mercury poisoning can occur as a result of occupational hazard or suicide attempt. This article presents a 36-year-old case admitted to emergency department (ED) due to exposure to metallic mercury. CASE PRESENTATION: A 36-year old woman presented to the ED with a three-day history of abdominal pain, diarrhea and fever. One week ago her daughter had brought mercury in the liquid form from the school. She had put it on the heating stove. One day later, her 14 month old sister baby got fever and died before admission to the hospital. Her blood pressure was 134/87 mmHg; temperature, 40.2 degrees C; heart rate 105 bpm and regular; respiration, 18 bpm; O2 saturation, 96%. Nothing was remarkable on examination and routine laboratory tests. As serine or urinary mercury levels could not be tested in the city, symptomatic chelation treatment with N-acetyl cysteine (NAC) was instituted with regard to presumptive diagnosis and history. At the 7th day of admission she was discharged without any sequelae or complaint. At the discharge day blood was drawn and sent for mercury levels which turned out to be 30 microg/dL (normal range: 0-10 microg/dL). CONCLUSION: Public education on poisoning and the potential hazards of mercury are of vital importance for community health. PMID- 20302611 TI - A case of high-grade leiomyosarcoma of the bladder with delayed onset and very poor prognosis. AB - Mesenchymal tumors represent a small number of bladder cancer cases. Leiomyosarcoma is the most common histology with over 100 cases reported in the whole literature. This tumor is been historically considered as highly aggressive and showing a poor prognosis. Despite very low survival rates showed in older reports, some authors indicate that some patients could have a better outcome. We report a review of the literature and a case of high-grade LMS of the bladder in a 68 years old woman. Diagnosis was delayed and disease was locally advanced. Symptoms and imaging of our case first oriented to a gynecologic condition with an adnexal or uterine origin of the mass, and, a genitourinary origin could be unveiled only intra-operatively. PMID- 20302610 TI - Differential effects of Paclitaxel on dendritic cell function. AB - BACKGROUND: The potential utility of dendritic cells (DC) as cancer vaccines has been established in early trials in human cancers. The concomitant administration of cytotoxic agents and DC vaccines has been previously avoided due to potential immune suppression by chemotherapeutics. Recent studies show that common chemotherapy agents positively influence adaptive and innate anti-tumour immune responses. RESULTS: We investigated the effects of paclitaxel on human DC biology in vitro. DCs appear to sustain a significant level of resistance to paclitaxel and maintain normal viability at concentrations of up to 100 micromol. In some cases this resistance against paclitaxel is significantly better than the level seen in tumour cell lines. Paclitaxel exposure led to a dose dependent increase in HLA class II expression equivalent to exposure to lipopolysaccharide (LPS), and a corresponding increase in proliferation of allogeneic T cells at the clinically relevant doses of paclitaxel. Increase in HLA-Class II expression induced by paclitaxel was not blocked by anti TLR-4 antibody. However, paclitaxel exposure reduced the endocytic capacity of DC but reduced the expression of key pro-inflammatory cytokines such as IL-12 and TNFalpha. Key morphological changes occurred when immature DC were cultured with 100 micromol paclitaxel. They became small rounded cells with stable microtubules, whereas there were little effects on LPS-matured DC. CONCLUSIONS: The effect of paclitaxel on human monocyte derived DC is complex, but in the clinical context of patients receiving preloaded and matured DC vaccines, its immunostimulatory potential and resistance to direct cytotoxicity by paclitaxel would indicate potential advantages to co administration with vaccines. PMID- 20302612 TI - DNIC-mediated analgesia produced by a supramaximal electrical or a high-dose formalin conditioning stimulus: roles of opioid and alpha2-adrenergic receptors. AB - BACKGROUND: Diffuse noxious inhibitory controls (DNIC) can be produced by different types of conditioning stimuli, but the analgesic properties and underlying mechanisms remain unclear. The aim of this study was to differentiate the induction of DNIC analgesia between noxious electrical and inflammatory conditioning stimuli. METHODS: First, rats subjected to either a supramaximal electrical stimulation or an injection of high-dose formalin in the hind limb were identified to have pain responses with behavioral evidence and spinal Fos immunoreactive profiles. Second, suppression of tail-flick latencies by the two noxious stimuli was assessed to confirm the presence of DNIC. Third, an opioid receptor antagonist (naloxone) and an alpha2-adrenoreceptor antagonist (yohimbine) were injected, intraperitoneally and intrathecally respectively, before conditioning noxious stimuli to test the involvement of descending inhibitory pathways in DNIC-mediated analgesia. RESULTS: An intramuscular injection of 100 microl of 5% formalin produced noxious behaviors with cumulative pain scores similar to those of 50 microl of 2% formalin in the paw. Both electrical and chemical stimulation significantly increased Fos expression in the superficial dorsal horns, but possessed characteristic distribution patterns individually. Both conditioning stimuli prolonged the tail-flick latencies indicating a DNIC response. However, the electrical stimulation-induced DNIC was reversed by yohimbine, but not by naloxone; whereas noxious formalin-induced analgesia was both naloxone- and yohimbine-reversible. CONCLUSIONS: It is demonstrated that DNIC produced by different types of conditioning stimuli can be mediated by different descending inhibitory controls, indicating the organization within the central nervous circuit is complex and possibly exhibits particular clinical manifestations. PMID- 20302613 TI - Physicochemical property distributions for accurate and rapid pairwise protein homology detection. AB - BACKGROUND: The challenge of remote homology detection is that many evolutionarily related sequences have very little similarity at the amino acid level. Kernel-based discriminative methods, such as support vector machines (SVMs), that use vector representations of sequences derived from sequence properties have been shown to have superior accuracy when compared to traditional approaches for the task of remote homology detection. RESULTS: We introduce a new method for feature vector representation based on the physicochemical properties of the primary protein sequence. A distribution of physicochemical property scores are assembled from 4-mers of the sequence and normalized based on the null distribution of the property over all possible 4-mers. With this approach there is little computational cost associated with the transformation of the protein into feature space, and overall performance in terms of remote homology detection is comparable with current state-of-the-art methods. We demonstrate that the features can be used for the task of pairwise remote homology detection with improved accuracy versus sequence-based methods such as BLAST and other feature based methods of similar computational cost. CONCLUSIONS: A protein feature method based on physicochemical properties is a viable approach for extracting features in a computationally inexpensive manner while retaining the sensitivity of SVM protein homology detection. Furthermore, identifying features that can be used for generic pairwise homology detection in lieu of family-based homology detection is important for applications such as large database searches and comparative genomics. PMID- 20302614 TI - Breast and cervical cancer screening among women in metropolitan areas of the United States by county-level commuting time to work and use of public transportation, 2004 and 2006. AB - BACKGROUND: Commuting times and behaviors have been associated with a variety of chronic disease outcomes and health behaviors. We examined the relationships between ecologic measures of commuting time and use of public transportation in relation to breast and cervical cancer screening among women in U.S. metropolitan areas who participated in the 2004 and 2006 Behavioral Risk Factor Surveillance System (BRFSS) surveys. METHODS: Self-reported county of residence was used to classify respondents as residents of metropolitan statistical areas (MSAs). Only BRFSS respondents who resided in the 39 MSAs with a population of > or = 1.5 million in 2007--representing a total of 337 counties--were included in this analysis. A total of 76,453 women aged > or = 40 years were included in analyses on mammography. Analyses on Pap testing were limited to women aged > or =18 years with no history of hysterectomy (n = 80,959). Area-based measures of socio economic status (SES) were obtained by utilizing county-level information from the 2000 U.S. Census. RESULTS: With adjustment for age, no important associations were observed between receipt of a recent mammogram and either a county-level measure of commute time or residence in an area where more residents had access to a car. Similarly, women living in counties where at least four percent of the residents used public transportation were as likely to have had a recent mammogram or Pap test compared with women in areas where less than four percent of residents used public transportation. However, women living in counties where < 2% of residents had no access to a car were somewhat more likely to have had a Pap test in the past 3 years than women in areas where > or = 3% of the residents had no access to a car (87.3% versus 84.5%; p-value for test for trend < 0.01). In multivariate analysis, living in a county with a median commute time of at least 30 minutes was not significantly associated with having had a Pap test in the past 3 years (adjusted odds ratio (OR) = 1.1, 95% CI 0.9-1.2, p = .50), or with having had a mammogram in the past 2 years (adjusted OR = 0.9, 95% CI 0.9 1.1, p = .28). A weak positive association was observed between residence in a county with less use of public transportation and having had a Pap test in the past 3 years, which was of borderline significance (adjusted OR 1.2, 95% CI 1.0 1.4, p = .05). CONCLUSIONS: In large U.S. metropolitan areas, transportation issues may play a role in whether a woman obtains cancer screening along with other factors (e.g., Hispanic ethnicity, low income, and no physician visit in the past year). In this contextual analysis, a longer commute time was not associated with breast and cervical cancer screening. PMID- 20302616 TI - Genetic heterogeneity of residual variance - estimation of variance components using double hierarchical generalized linear models. AB - BACKGROUND: The sensitivity to microenvironmental changes varies among animals and may be under genetic control. It is essential to take this element into account when aiming at breeding robust farm animals. Here, linear mixed models with genetic effects in the residual variance part of the model can be used. Such models have previously been fitted using EM and MCMC algorithms. RESULTS: We propose the use of double hierarchical generalized linear models (DHGLM), where the squared residuals are assumed to be gamma distributed and the residual variance is fitted using a generalized linear model. The algorithm iterates between two sets of mixed model equations, one on the level of observations and one on the level of variances. The method was validated using simulations and also by re-analyzing a data set on pig litter size that was previously analyzed using a Bayesian approach. The pig litter size data contained 10,060 records from 4,149 sows. The DHGLM was implemented using the ASReml software and the algorithm converged within three minutes on a Linux server. The estimates were similar to those previously obtained using Bayesian methodology, especially the variance components in the residual variance part of the model. CONCLUSIONS: We have shown that variance components in the residual variance part of a linear mixed model can be estimated using a DHGLM approach. The method enables analyses of animal models with large numbers of observations. An important future development of the DHGLM methodology is to include the genetic correlation between the random effects in the mean and residual variance parts of the model as a parameter of the DHGLM. PMID- 20302615 TI - Staying well after depression: trial design and protocol. AB - BACKGROUND: Depression is often a chronic relapsing condition, with relapse rates of 50-80% in those who have been depressed before. This is particularly problematic for those who become suicidal when depressed since habitual recurrence of suicidal thoughts increases likelihood of further acute suicidal episodes. Therefore the question how to prevent relapse is of particular urgency in this group. METHODS/DESIGN: This trial compares Mindfulness-Based Cognitive Therapy (MBCT), a novel form of treatment combining mindfulness meditation and cognitive therapy for depression, with both Cognitive Psycho-Education (CPE), an equally plausible cognitive treatment but without meditation, and treatment as usual (TAU). It will test whether MBCT reduces the risk of relapse in recurrently depressed patients and the incidence of suicidal symptoms in those with a history of suicidality who do relapse. It recruits participants, screens them by telephone for main inclusion and exclusion criteria and, if they are eligible, invites them to a pre-treatment session to assess eligibility in more detail. This trial allocates eligible participants at random between MBCT and TAU, CPE and TAU, and TAU alone in a ratio of 2:2:1, stratified by presence of suicidal ideation or behaviour and current anti-depressant use. We aim to recruit sufficient participants to allow for retention of 300 following attrition. We deliver both active treatments in groups meeting for two hours every week for eight weeks. We shall estimate effects on rates of relapse and suicidal symptoms over 12 months following treatment and assess clinical status immediately after treatment, and three, six, nine and twelve months thereafter. DISCUSSION: This will be the first trial of MBCT to investigate whether MCBT is effective in preventing relapse to depression when compared with a control psychological treatment of equal plausibility; and to explore the use of MBCT for the most severe recurrent depression--that in people who become suicidal when depressed. PMID- 20302617 TI - Local impact of temperature and precipitation on West Nile virus infection in Culex species mosquitoes in northeast Illinois, USA. AB - BACKGROUND: Models of the effects of environmental factors on West Nile virus disease risk have yielded conflicting outcomes. The role of precipitation has been especially difficult to discern from existing studies, due in part to habitat and behavior characteristics of specific vector species and because of differences in the temporal and spatial scales of the published studies. We used spatial and statistical modeling techniques to analyze and forecast fine scale spatial (2000 m grid) and temporal (weekly) patterns of West Nile virus mosquito infection relative to changing weather conditions in the urban landscape of the greater Chicago, Illinois, region for the years from 2004 to 2008. RESULTS: Increased air temperature was the strongest temporal predictor of increased infection in Culex pipiens and Culex restuans mosquitoes, with cumulative high temperature differences being a key factor distinguishing years with higher mosquito infection and higher human illness rates from those with lower rates. Drier conditions in the spring followed by wetter conditions just prior to an increase in infection were factors in some but not all years. Overall, 80% of the weekly variation in mosquito infection was explained by prior weather conditions. Spatially, lower precipitation was the most important variable predicting stronger mosquito infection; precipitation and temperature alone could explain the pattern of spatial variability better than could other environmental variables (79% explained in the best model). Variables related to impervious surfaces and elevation differences were of modest importance in the spatial model. CONCLUSION: Finely grained temporal and spatial patterns of precipitation and air temperature have a consistent and significant impact on the timing and location of increased mosquito infection in the northeastern Illinois study area. The use of local weather data at multiple monitoring locations and the integration of mosquito infection data from numerous sources across several years are important to the strength of the models presented. The other spatial environmental factors that tended to be important, including impervious surfaces and elevation measures, would mediate the effect of rainfall on soils and in urban catch basins. Changes in weather patterns with global climate change make it especially important to improve our ability to predict how inter-related local weather and environmental factors affect vectors and vector-borne disease risk.Local impact of temperature and precipitation on West Nile virus infection in Culex species mosquitoes in northeast Illinois, USA. PMID- 20302619 TI - Efficacy of osteopathic manipulation as an adjunctive treatment for hospitalized patients with pneumonia: a randomized controlled trial. AB - BACKGROUND: The Multicenter Osteopathic Pneumonia Study in the Elderly (MOPSE) is a registered, double-blinded, randomized, controlled trial designed to assess the efficacy of osteopathic manipulative treatment (OMT) as an adjunctive treatment in elderly patients with pneumonia. METHODS: 406 subjects aged >/= 50 years hospitalized with pneumonia at 7 community hospitals were randomized using concealed allocation to conventional care only (CCO), light-touch treatment (LT), or OMT groups. All subjects received conventional treatment for pneumonia. OMT and LT groups received group-specific protocols for 15 minutes, twice daily until discharge, cessation of antibiotics, respiratory failure, death, or withdrawal from the study. The primary outcomes were hospital length of stay (LOS), time to clinical stability, and a symptomatic and functional recovery score. RESULTS: Intention-to-treat (ITT) analysis (n = 387) found no significant differences between groups. Per-protocol (PP) analysis (n = 318) found a significant difference between groups (P = 0.01) in LOS. Multiple comparisons indicated a reduction in median LOS (95% confidence interval) for the OMT group (3.5 [3.2 4.0] days) versus the CCO group (4.5 [3.9-4.9] days), but not versus the LT group (3.9 [3.5-4.8] days). Secondary outcomes of duration of intravenous antibiotics and treatment endpoint were also significantly different between groups (P = 0.05 and 0.006, respectively). Duration of intravenous antibiotics and death or respiratory failure were lower for the OMT group versus the CCO group, but not versus the LT group. CONCLUSIONS: ITT analysis found no differences between groups. PP analysis found significant reductions in LOS, duration of intravenous antibiotics, and respiratory failure or death when OMT was compared to CCO. Given the prevalence of pneumonia, adjunctive OMT merits further study. PMID- 20302618 TI - Review of Journal of Cardiovascular Magnetic Resonance 2009. AB - There were 56 articles published in the Journal of Cardiovascular Magnetic Resonance in 2009. The editors were impressed with the high quality of the submissions, of which our acceptance rate was about 40%. In accordance with open access publishing, the articles go on-line as they are accepted with no collating of the articles into sections or special thematic issues. We have therefore chosen to briefly summarise the papers in this article for quick reference for our readers in broad areas of interest, which we feel will be useful to practitioners of cardiovascular magnetic resonance (CMR). In some cases where it is considered useful, the articles are also put into the wider context with a short narrative and recent CMR references. It has been a privilege to serve as the Editor of the JCMR this past year. I hope that you find the open-access system increases wider reading and citation of your papers, and that you will continue to send your quality manuscripts to JCMR for publication. PMID- 20302620 TI - Osteopathic manipulative treatment for pneumonia. AB - The pneumonias due to infection continue to be a meaningful threat to the health and viability of persons, particularly those in high risk groups: children, the aged and the debilitated. Noll and colleagues provide us with the results of a well-designed and well-executed multi-institutional controlled clinical trial to evaluate the efficacy of osteopathic manipulative treatment (OMT) in the treatment of pneumonia. The data obtained indicate that by intention-to-treat analysis, the addition of OMT to conventional care did not improve the designated outcomes when compared to conventional care only. A disappointing but important finding. However, by per-protocol analysis, the addition of OMT or of light touch decreased length of hospital stay, the duration of intravenous antibiotics and the incidence of respiratory failure and death relative to conventional care only. Further study is called for to explain these surprising results.Meeting the need for randomized clinical trials of the role and efficacy of OMT is a responsibility of high priority for the osteopathic profession in this age of evidence-based medicine. The American Osteopathic Association (AOA) needs to consider reinstating a dues-generated financial set-aside both to increase its support of osteopathic research and to initiate a program of physician investigator career development awards to recruit and help establish osteopathic clinical investigators in a career in translational and clinical research. PMID- 20302621 TI - Ubiquitin carboxy-terminal hydrolase L1 (UCHL1) S18Y polymorphism in Alzheimer's disease. AB - Alzheimer's disease (AD) is characterized by protein aggregates, i.e. senile plaques and neurofibrillary tangles. The ubiquitin-proteasome system has been proposed a role in proteolytic removal of these protein aggregates. Ubiquitin carboxy-terminal hydrolase L1 (UCHL1) is a de-ubiquitinating enzyme with important functions in recycling of ubiquitin. The S18Y polymorphism of the UCHL1 gene confers protection against Parkinson's disease. In this study, the genotype and allele frequencies of the UCHL1 S18Y polymorphism were investigated in 452 AD patients and 234 control subjects, recruited from four memory clinics in Sweden. Using a binary logistic regression model including UCHL1 allele A and APOE epsilon4 allele positivity, age and sex as covariates with AD diagnosis as dependent variable, an adjusted OR of 0.82 ([95% CI 0.55-1.24], P = 0.35) was obtained for a positive UCHL1 allele A carrier status. The present study thus do not support a protective effect of the UCHL1 S18Y polymorphism against AD. PMID- 20302623 TI - Swimming suppresses hepatic vitellogenesis in European female silver eels as shown by expression of the estrogen receptor 1, vitellogenin1 and vitellogenin2 in the liver. AB - BACKGROUND: When European silver eels (Anguilla anguilla) venture into the Atlantic Ocean for their 6,000 km semelparous spawning run to the Sargasso Sea, they are still in a prepubertal stage. Further sexual development appears to be blocked by dopaminergic inhibition of hypothalamus and pituitary activity. Recently, we found that swimming for several weeks in freshwater stimulated the incorporation of fat droplets in the oocytes. So, it was hypothesized that long term swimming in seawater would release the inhibition further and would also stimulate the production of vitellogenin by the liver. METHODS: For this study a swim-flume was constructed to allow simulated migration of migratory female silver eels for 3 months (1,420 km) in natural seawater at 20 degrees C. Primers were designed for polymerase chain reactions to measure the mRNA expression of estrogen receptor 1 (esr1), vitellogenin1 (vtg1) and vitellogenin2 (vtg2) genes in the liver of European female silver eels. RESULTS: In comparison to resting eels, swimming eels showed a diminished expression of esr1, vtg1 and vtg2 in the liver. They also had lower plasma calcium (Ca; indicative of vitellogenin) levels in their blood. This showed that vitellogenesis is more strongly suppressed in swimming than in resting eels. However, when eels were subsequently stimulated by 3 weekly carp pituitary extract injections, the expression of the same genes and plasma levels of Ca strongly increased in both groups to similar levels, thus equalizing the initial differences between resting and swimming. CONCLUSIONS: It is concluded that vitellogenesis remains suppressed during resting and even more during swimming. The fact that swimming stimulates fat deposition in the oocytes but suppresses vitellogenesis indicates that these events are separated in nature and occur sequentially. Swimming-suppressed vitellogenesis may imply that in nature eels undergo vitellogenesis and final maturation near or at the spawning grounds. PMID- 20302622 TI - Genetic evidence supports linguistic affinity of Mlabri--a hunter-gatherer group in Thailand. AB - BACKGROUND: The Mlabri are a group of nomadic hunter-gatherers inhabiting the rural highlands of Thailand. Little is known about the origins of the Mlabri and linguistic evidence suggests that the present-day Mlabri language most likely arose from Tin, a Khmuic language in the Austro-Asiatic language family. This study aims to examine whether the genetic affinity of the Mlabri is consistent with this linguistic relationship, and to further explore the origins of this enigmatic population. RESULTS: We conducted a genome-wide analysis of genetic variation using more than fifty thousand single nucleotide polymorphisms (SNPs) typed in thirteen population samples from Thailand, including the Mlabri, Htin and neighboring populations of the Northern Highlands, speaking Austro-Asiatic, Tai-Kadai and Hmong-Mien languages. The Mlabri population showed higher LD and lower haplotype diversity when compared with its neighboring populations. Both model-free and Bayesian model-based clustering analyses indicated a close genetic relationship between the Mlabri and the Htin, a group speaking a Tin language. CONCLUSION: Our results strongly suggested that the Mlabri share more recent common ancestry with the Htin. We thus provided, to our knowledge, the first genetic evidence that supports the linguistic affinity of Mlabri, and this association between linguistic and genetic classifications could reflect the same past population processes. PMID- 20302624 TI - Quality of life measurement in women with cervical cancer: implications for Chinese cervical cancer survivors. AB - BACKGROUND: Women with cervical cancer now have relatively good 5-year survival rates. Better survival rates have driven the paradigm in cancer care from a medical illness model to a wellness model, which is concerned with the quality of women's lives as well as the length of survival. Thus, the assessment of quality of life among cervical cancer survivors is increasingly paramount for healthcare professionals. The purposes of this review were to describe existing validated quality of life instruments used in cervical cancer survivors, and to reveal the implications of quality of life measurement for Chinese cervical cancer survivors. METHODS: A literature search of five electronic databases was conducted using the terms cervical/cervix cancer, quality of life, survivors, survivorship, measurement, and instruments. Articles published in either English or Chinese from January 2000 to June 2009 were searched. Only those adopting an established quality of life instrument for use in cervical cancer survivors were included. RESULTS: A total of 11 validated multidimensional quality of life instruments were identified from 41 articles. These instruments could be classified into four categories: generic, cancer-specific, cancer site-specific and cancer survivor-specific instruments. With internal consistency varying from 0.68-0.99, the test-retest reliability ranged from 0.60-0.95 based on the test of the Pearson coefficient. One or more types of validity supported the construct validity. Although all these instruments met the minimum requirements of reliability and validity, the original versions of these instruments were mainly in English. CONCLUSION: Selection of an instrument should consider the purpose of investigation, take its psychometric properties into account, and consider the instrument's origin and comprehensiveness. As quality of life can be affected by culture, studies assessing the quality of life of cervical cancer survivors in China or other non-English speaking countries should choose or develop instruments relevant to their own cultural context. There is a need to develop a comprehensive quality of life instrument for Chinese cervical cancer survivors across the whole survivorship, including immediately after diagnosis and for short- (less than 5 years) and long-term (more than 5 years) survivorship. PMID- 20302625 TI - High ANC coverage and low skilled attendance in a rural Tanzanian district: a case for implementing a birth plan intervention. AB - BACKGROUND: In Tanzania, more than 90% of all pregnant women attend antenatal care at least once and approximately 62% four times or more, yet less than five in ten receive skilled delivery care at available health units. We conducted a qualitative study in Ngorongoro district, Northern Tanzania, in order to gain an understanding of the health systems and socio-cultural factors underlying this divergent pattern of high use of antenatal services and low use of skilled delivery care. Specifically, the study examined beliefs and behaviors related to antenatal, labor, delivery and postnatal care among the Maasai and Watemi ethnic groups. The perspectives of health care providers and traditional birth attendants on childbirth and the factors determining where women deliver were also investigated. METHODS: Twelve key informant interviews and fifteen focus group discussions were held with Maasai and Watemi women, traditional birth attendants, health care providers, and community members. Principles of the grounded theory approach were used to elicit and assess the various perspectives of each group of participants interviewed. RESULTS: The Maasai and Watemi women's preferences for a home birth and lack of planning for delivery are reinforced by the failure of health care providers to consistently communicate the importance of skilled delivery and immediate post-partum care for all women during routine antenatal visits. Husbands typically serve as gatekeepers of women's reproductive health in the two groups - including decisions about where they will deliver- yet they are rarely encouraged to attend antenatal sessions. While husbands are encouraged to participate in programs to prevent maternal-to-child transmission of HIV, messages about the importance of skilled delivery care for all women are not given emphasis. CONCLUSIONS: Increasing coverage of skilled delivery care and achieving the full implementation of Tanzania's Focused Antenatal Care Package in Ngorongoro depends upon improved training and monitoring of health care providers, and greater family participation in antenatal care visits. PMID- 20302626 TI - ASB9 interacts with ubiquitous mitochondrial creatine kinase and inhibits mitochondrial function. AB - BACKGROUND: The ankyrin repeat and suppressor of cytokine signalling (SOCS) box proteins (Asbs) are a large protein family implicated in diverse biological processes including regulation of proliferation and differentiation. The SOCS box of Asb proteins is important in a ubiquitination-mediated proteolysis pathway. Here, we aimed to evaluate expression and function of human Asb-9 (ASB9). RESULTS: We found that a variant of ASB9 that lacks the SOCS box (ASB9DeltaSOCS) was naturally detected in human cell lines but not in peripheral blood mononuclear cells or normal hepatocytes. We also identified ubiquitous mitochondrial creatine kinase (uMtCK) as a new target of ASB9 in human embryonic kidney 293 (HEK293) cells. The ankyrin repeat domains of ASB9 can associate with the substrate binding site of uMtCK in a SOCS box-independent manner. The overexpression of ASB9, but not ASB9DeltaSOCS, induces ubiquitination of uMtCK. ASB9 and ASB9DeltaSOCS can interact and colocalise with uMtCK in the mitochondria. However, only expression of ASB9 induced abnormal mitochondrial structure and a decrease of mitochondrial membrane potential. Furthermore, the creatine kinase activities and cell growth were significantly reduced by ASB9 but not by ASB9DeltaSOCS. CONCLUSIONS: ASB9 interacts with the creatine kinase system and negatively regulates cell growth. The differential expression and function of ASB9 and ASB9DeltaSOCS may be a key factor in the growth of human cell lines and primary cells. PMID- 20302627 TI - A novel approach to investigate tissue-specific trinucleotide repeat instability. AB - BACKGROUND: In Huntington's disease (HD), an expanded CAG repeat produces characteristic striatal neurodegeneration. Interestingly, the HD CAG repeat, whose length determines age at onset, undergoes tissue-specific somatic instability, predominant in the striatum, suggesting that tissue-specific CAG length changes could modify the disease process. Therefore, understanding the mechanisms underlying the tissue specificity of somatic instability may provide novel routes to therapies. However progress in this area has been hampered by the lack of sensitive high-throughput instability quantification methods and global approaches to identify the underlying factors. RESULTS: Here we describe a novel approach to gain insight into the factors responsible for the tissue specificity of somatic instability. Using accurate genetic knock-in mouse models of HD, we developed a reliable, high-throughput method to quantify tissue HD CAG repeat instability and integrated this with genome-wide bioinformatic approaches. Using tissue instability quantified in 16 tissues as a phenotype and tissue microarray gene expression as a predictor, we built a mathematical model and identified a gene expression signature that accurately predicted tissue instability. Using the predictive ability of this signature we found that somatic instability was not a consequence of pathogenesis. In support of this, genetic crosses with models of accelerated neuropathology failed to induce somatic instability. In addition, we searched for genes and pathways that correlated with tissue instability. We found that expression levels of DNA repair genes did not explain the tissue specificity of somatic instability. Instead, our data implicate other pathways, particularly cell cycle, metabolism and neurotransmitter pathways, acting in combination to generate tissue-specific patterns of instability. CONCLUSION: Our study clearly demonstrates that multiple tissue factors reflect the level of somatic instability in different tissues. In addition, our quantitative, genome-wide approach is readily applicable to high-throughput assays and opens the door to widespread applications with the potential to accelerate the discovery of drugs that alter tissue instability. PMID- 20302629 TI - Identification of a deep intronic mutation in the COL6A2 gene by a novel custom oligonucleotide CGH array designed to explore allelic and genetic heterogeneity in collagen VI-related myopathies. AB - BACKGROUND: Molecular characterization of collagen-VI related myopathies currently relies on standard sequencing, which yields a detection rate approximating 75-79% in Ullrich congenital muscular dystrophy (UCMD) and 60-65% in Bethlem myopathy (BM) patients as PCR-based techniques tend to miss gross genomic rearrangements as well as copy number variations (CNVs) in both the coding sequence and intronic regions. METHODS: We have designed a custom oligonucleotide CGH array in order to investigate the presence of CNVs in the coding and non-coding regions of COL6A1, A2, A3, A5 and A6 genes and a group of genes functionally related to collagen VI. A cohort of 12 patients with UCMD/BM negative at sequencing analysis and 2 subjects carrying a single COL6 mutation whose clinical phenotype was not explicable by inheritance were selected and the occurrence of allelic and genetic heterogeneity explored. RESULTS: A deletion within intron 1A of the COL6A2 gene, occurring in compound heterozygosity with a small deletion in exon 28, previously detected by routine sequencing, was identified in a BM patient. RNA studies showed monoallelic transcription of the COL6A2 gene, thus elucidating the functional effect of the intronic deletion. No pathogenic mutations were identified in the remaining analyzed patients, either within COL6A genes, or in genes functionally related to collagen VI. CONCLUSIONS: Our custom CGH array may represent a useful complementary diagnostic tool, especially in recessive forms of the disease, when only one mutant allele is detected by standard sequencing. The intronic deletion we identified represents the first example of a pure intronic mutation in COL6A genes. PMID- 20302630 TI - Prevalence of Helicobacter pylori vacA, cagA, iceA and oipA genotypes in Tunisian patients. AB - BACKGROUND: Distinct virulence factors of H. pylori have been described: the vaculating cytotoxin (vacA), the cytotoxin associated gene (cagA), the induced by contact with epithelium factor Antigen (iceA gene) and the outer membrane protein oipA. In Tunisia, there are no data regarding the pattern of H. pylori genotypes; therefore, this prospective and multicentre study was the first to be done in Tunisia and aimed to investigate the prevalence of the vacA, cagA, iceA and oipA genotypes of H. pylori isolates from Tunisian patients with peptic ulceration, gastric cancer, MALT lymphoma and gastritis. METHODS: H. pylori was cultured from endoscopic biopsies obtained from 281 Tunisian patients. The vacA alleles, cagA, iceA and oipA genotypes were determined by PCR. RESULTS: The vacA s1m1, s1m2 and s2m2 were respectively found in 10.7%, 12.5% and 45.6% of strains. The s2m1 genotype was not detected in our study. The cagA was found in 61.6% of isolates. The iceA1 and the iceA2 genotypes were respectively isolated in 60.2% and in 16% of strains. The oipA genotype was detected in 90.8% of strains. Considering the vacA and iceA genotypes, the presence of multiple H. pylori strains in a single biopsy specimen was found respectively in 31.4% and 23.8%. The comparison between strains isolated from antrum and fundus showed that Tunisian patients were infected with two or more strains of different cagA, vacA, iceA and oipA genotypes and the discordance was respectively in 9.6%, 4.6%, 8.9% and 8.5% of strains. CONCLUSION: Our results showed that in 46% (131 strains among 281), the H. pylori strains were highly virulent in relation of the three or four virulent factors they could carry. These finding were described before in the literature. Tunisian patients were colonized by one or multiple strains of H. pylori in the same time in relation of presence of vacA m1/m2 and iceA1/iceA2 in the same biopsy. The discordance between strains isolated from antrum and fundus was high, and it is in favour of multicolonization. PMID- 20302631 TI - Analysing time course microarray data using Bioconductor: a case study using yeast2 Affymetrix arrays. AB - BACKGROUND: Large scale microarray experiments are becoming increasingly routine, particularly those which track a number of different cell lines through time. This time-course information provides valuable insight into the dynamic mechanisms underlying the biological processes being observed. However, proper statistical analysis of time-course data requires the use of more sophisticated tools and complex statistical models. FINDINGS: Using the open source CRAN and Bioconductor repositories for R, we provide example analysis and protocol which illustrate a variety of methods that can be used to analyse time-course microarray data. In particular, we highlight how to construct appropriate contrasts to detect differentially expressed genes and how to generate plausible pathways from the data. A maintained version of the R commands can be found at http://www.mas.ncl.ac.uk/~ncsg3/microarray/. CONCLUSIONS: CRAN and Bioconductor are stable repositories that provide a wide variety of appropriate statistical tools to analyse time course microarray data. PMID- 20302628 TI - A focus on intra-abdominal infections. AB - Complicated intra-abdominal infections are an important cause of morbidity and are frequently associated with poor prognosis, particularly in higher risk patients.Well defined evidence-based recommendations for intra-abdominal infections treatment are partially lacking because of the limited number of randomized-controlled trials.Factors consistently associated with poor outcomes in patients with intra-abdominal infections include increased illness severity, failed source control, inadequate empiric antimicrobial therapy and healthcare acquired infection.Early prognostic evaluation of complicated intra-abdominal infections is important to select high-risk patients for more aggressive therapeutic procedures.The cornerstones in the management of complicated intra abdominal infections are both source control and antibiotic therapy.The timing and the adequacy of source control are the most important issues in the management of intra-abdominal infections, because inadequate and late control of septic source may have a negative effect on the outcomes.Recent advances in interventional and more aggressive techniques could significantly decrease the morbidity and mortality of physiologically severe complicated intra-abdominal infections, even if these are still being debated and are yet not validated by limited prospective trials.Empiric antimicrobial therapy is nevertheless important in the overall management of intra-abdominal infections. Inappropriate antibiotic therapy may result in poor patient outcomes and in the appearance of bacterial resistance.Antimicrobial management is generally standardised and many regimens, either with monotherapy or combination therapy, have proven their efficacy. Routine coverage especially against Enterococci and candida spp is not always recommended, but can be useful in particular clinical conditions. A de escalation approach may be recommended in patients with specific risk factors for multidrug resistant infections such as immunodeficiency and prolonged antibacterial exposure.Therapy should focus on the obtainment of adequate source control and adequate use of antimicrobial therapy dictated by individual patient risk factors. Other critical issues remain debated and more controversies are still open mainly because of the limited number of randomized controlled trials. PMID- 20302632 TI - Dynamics of serum antibodies to and load of porcine circovirus type 2 (PCV2) in pigs in three finishing herds, affected or not by postweaning multisystemic wasting syndrome. AB - BACKGROUND: Despite that PMWS commonly affects pigs aged eight to sixteen weeks; most studies of PMWS have been conducted during the period before transfer to finishing herds. This study focused on PCV2 load and antibody dynamics in finishing herds with different PMWS status. METHODS: Sequentially collected blood samples from 40 pigs in each of two Swedish (A and B) and one Norwegian (C) finishing herds were analysed for serum PCV2-load and -antibodies and saliva cortisol. The two Swedish herds differed in PMWS status, despite receiving animals from the same sow pool (multi-site production). However, the PMWS-deemed herd (A) had previously also received pigs from the spot market. RESULTS: The initial serum PCV2 load was similar in the two Swedish herds. In herd A, it peaked after two weeks in the finishing herd and a high number of the pigs had serum PCV2 levels above 107 per ml. The antibody titres increased continually with exception for the pigs that developed PMWS, that had initially low and then declining antibody levels. Pigs in the healthy herd B also expressed high titres of antibodies to PCV2 on arrival but remained at that level throughout the study whereas the viral load steadily decreased. No PCV2 antibodies and only low amounts of PCV2 DNA were detected in serum collected during the first five weeks in the PMWS-free herd C. Thereafter a peak in serum PCV2 load accompanied by an antibody response was recorded. PCV2 from the two Swedish herds grouped into genotype PCV2b whereas the Norwegian isolate grouped into PCV2a. Cortisol levels were lower in herd C than in herds A and B. CONCLUSIONS: The most obvious difference between the Swedish finishing herds and the Norwegian herd was the time of infection with PCV2 in relation to the time of allocation, as well as the genotype of PCV2. Clinical PMWS was preceded by low levels of serum antibodies and a high load of PCV2 but did not develop in all such animals. It is notable that herd A became affected by PMWS after errors in management routine, emphasising the importance of proper hygiene and general disease-preventing measures. PMID- 20302633 TI - Effect of hyperbaric oxygen on mesenchymal stem cells for lumbar fusion in vivo. AB - BACKGROUND: Hyperbaric oxygen (HBO) therapy has been proved in improving bone healing, but its effects on mesenchymal stem cells (MSCs) in vivo is not clear. The aims of this study are to clarify whether the HBO therapy has the same enhancing effect on MSCs with regard to bone formation and maturation and to ascertain whether the transplanted MSCs survive in the grafted area and contribute to new bone formation. METHODS: Twenty-three adult rabbits underwent posterolateral fusion at L4-L5 level. The animals were divided into three groups according to the material implanted and subsequent treatment: (1) Alginate carrier (n = 6); (2) Alginate-MSCs composite (n = 11); and (3) Alginate-MSCs composite with HBO therapy (n = 6). After 12 weeks, spine fusion was examined using radiographic examination, manual testing, and histological examination. Using a PKH fluorescence labeling system, whether the transplanted MSCs survived and contributed to new bone formation in the grafted area after HBO therapy was also examined. RESULTS: The bilateral fusion areas in each animal were evaluated independently. By radiographic examination and manual palpation, union for the Alginate, Alginate-MSCs, and Alginate-MSCs-HBO groups was 0 of 12, 10 of 22, and 6 of 12 respectively. The difference between the Alginate-MSCs and Alginate-MSCs HBO groups was not significant (P = 0.7997). The fluorescence microscopy histological analysis indicated that the transplanted PKH67-labeled MSCs survived and partly contributed to new bone formation in the grafted area. CONCLUSIONS: This study demonstrated that the preconditioned MSCs could survive and yield bone formation in the grafted area. HBO therapy did not enhance the osteogenic ability of MSCs and improve the success of spine fusion in the rabbit model. Although there was no significant effect of HBO therapy on MSCs for spine fusion, the study encourages us to research a more basic approach for determining the optimal oxygen tension and pressure that are required to maintain and enhance the osteogenic ability of preconditioned MSCs. Further controlled in vivo and in vitro studies are required for achieving a better understanding of the effect of HBO treatment on MSCs. PMID- 20302634 TI - A Canadian naturalistic study of a community-based cohort treated for bipolar disorder. AB - BACKGROUND: Bipolar illness is associated with significant psychosocial morbidity and health resource utilization. Second generation antipsychotics, used alone or in combination with mood stabilizers are effective in treating acute mania in community settings. This study was designed to compare the change in clinical parameters and resource utilization at one month in a group of patients who required treatment intervention for exacerbation of mania. The clinical response at one year was also evaluated. METHODS: 496 patients were enrolled at 75 psychiatric practices across Canada. The Olanzapine cohort (n = 287) included patients who had olanzapine added to their medication regimen or the dose of olanzapine increased. The Other cohort (n = 209) had a medication other than olanzapine added or the dose adjusted. Changes from baseline in the Young Mania Rating Scale (YMRS), Montgomery Asberg Depression Rating Scale, Beck Anxiety Inventory and SF-12 Health Survey were compared at one month using ANCOVA. Categorical variables at one month for health resource utilization, employment status, abuse/dependency, and the number of suicide attempts were compared using Fisher's Exact test. Patients were followed for one year and a subgroup was evaluated. RESULTS: At one month, patients in the Olanzapine cohort recorded a mean reduction in the YMRS of 11.5, significantly greater than the mean reduction in the Other cohort of 9.7 (ANCOVA P = 0.002). The Olanzapine cohort was significantly improved compared to the Other cohort on the scales for depression and anxiety and did not experience the deterioration in physical functioning seen in the Other cohort. No significant differences were detected in health-related quality-of-life measures, employment status, drug abuse/dependency, number of suicide attempts, mental functioning, emergency room visits or inpatient psychiatric hospitalizations. In a subgroup treated for 12 months with a single second generation antipsychotic, improvements in illness severity measures were maintained with no evidence of significant differences among the antipsychotics. CONCLUSIONS: Patients with bipolar disorder requiring treatment intervention for exacerbation of mania in the community setting responded to olanzapine at one month. In a subset analysis, second generation antipsychotic treatment continued to be beneficial in reducing bipolar symptoms at one year. PMID- 20302635 TI - Microrna profiling analysis of differences between the melanoma of young adults and older adults. AB - BACKGROUND: This study represents the first attempt to perform a profiling analysis of the intergenerational differences in the microRNAs (miRNAs) of primary cutaneous melanocytic neoplasms in young adult and older age groups. The data emphasize the importance of these master regulators in the transcriptional machinery of melanocytic neoplasms and suggest that differential levels of expressions of these miRs may contribute to differences in phenotypic and pathologic presentation of melanocytic neoplasms at different ages. METHODS: An exploratory miRNA analysis of 666 miRs by low density microRNA arrays was conducted on formalin fixed and paraffin embedded tissues (FFPE) from 10 older adults and 10 young adults including conventional melanoma and melanocytic neoplasms of uncertain biological significance. Age-matched benign melanocytic nevi were used as controls. RESULTS: Primary melanoma in patients greater than 60 years old was characterized by the increased expression of miRs regulating TLR MyD88-NF-kappaB pathway (hsa-miR-199a), RAS/RAB22A pathway (hsa-miR-204); growth differentiation and migration (hsa-miR337), epithelial mesenchymal transition (EMT) (let-7b, hsa-miR-10b/10b*), invasion and metastasis (hsa-miR-10b/10b*), hsa miR-30a/e*, hsa-miR-29c*; cellular matrix components (hsa-miR-29c*); invasion cytokinesis (hsa-miR-99b*) compared to melanoma of younger patients. MiR-211 was dramatically downregulated compared to nevi controls, decreased with increasing age and was among the miRs linked to metastatic processes. Melanoma in young adult patients had increased expression of hsa-miR-449a and decreased expression of hsa-miR-146b, hsa-miR-214*. MiR-30a* in clinical stages I-II adult and pediatric melanoma could predict classification of melanoma tissue in the two extremes of age groups. Although the number of cases is small, positive lymph node status in the two age groups was characterized by the statistically significant expression of hsa-miR-30a* and hsa-miR-204 (F-test, p-value < 0.001). CONCLUSIONS: Our findings, although preliminary, support the notion that the differential biology of melanoma at the extremes of age is driven, in part, by deregulation of microRNA expression and by fine tuning of miRs that are already known to regulate cell cycle, inflammation, Epithelial-Mesenchymal Transition (EMT)/stroma and more specifically genes known to be altered in melanoma. Our analysis reveals that miR expression differences create unique patterns of frequently affected biological processes that clearly distinguish old age from young age melanomas. This is a novel characterization of the miRnomes of melanocytic neoplasms at two extremes of age and identifies potential diagnostic and clinico-pathologic biomarkers that may serve as novel miR-based targeted modalities in melanoma diagnosis and treatment. PMID- 20302636 TI - Genotype networks in metabolic reaction spaces. AB - BACKGROUND: A metabolic genotype comprises all chemical reactions an organism can catalyze via enzymes encoded in its genome. A genotype is viable in a given environment if it is capable of producing all biomass components the organism needs to survive and reproduce. Previous work has focused on the properties of individual genotypes while little is known about how genome-scale metabolic networks with a given function can vary in their reaction content. RESULTS: We here characterize spaces of such genotypes. Specifically, we study metabolic genotypes whose phenotype is viability in minimal chemical environments that differ in their sole carbon sources. We show that regardless of the number of reactions in a metabolic genotype, the genotypes of a given phenotype typically form vast, connected, and unstructured sets -- genotype networks -- that nearly span the whole of genotype space. The robustness of metabolic phenotypes to random reaction removal in such spaces has a narrow distribution with a high mean. Different carbon sources differ in the number of metabolic genotypes in their genotype network; this number decreases as a genotype is required to be viable on increasing numbers of carbon sources, but much less than if metabolic reactions were used independently across different chemical environments. CONCLUSIONS: Our work shows that phenotype-preserving genotype networks have generic organizational properties and that these properties are insensitive to the number of reactions in metabolic genotypes. PMID- 20302638 TI - Assisted injection in outdoor venues: an observational study of risks and implications for service delivery and harm reduction programming. AB - BACKGROUND: Assisted injection and public injection have both been associated with a variety of individual harms including an increased risk of HIV infection. As a means of informing local IDU-driven interventions that target or seek to address assisted injection, we examined the correlates of receiving assistance with injecting in outdoor settings among a cohort of persons who inject drugs (IDU). METHODS: Using data from the Vancouver Injection Drug Users Study (VIDUS), an observational cohort study of IDU, generalized estimating equations (GEE) were performed to examine socio-demographic and behavioural factors associated with reports of receiving assistance with injecting in outdoor settings. RESULTS: From January 2004 to December 2005, a total of 620 participants were eligible for the present analysis. Our study included 251 (40.5%) women and 203 (32.7%) self identified Aboriginal participants. The proportion of participants who reported assisted injection outdoors ranged over time between 8% and 15%. Assisted injection outdoors was independently and positively associated with being female (Adjusted Odds Ratio (AOR) = 1.74, 95% Confidence Intervals (CI): 1.21-2.50), daily cocaine injection (AOR = 1.70, 95% CI: 1.29-2.24), and sex trade involvement (AOR = 1.44, 95% CI: 1.00-2.06) and was negatively associated with Aboriginal ethnicity (AOR = 0.58, 95% CI: 0.41-0.82). CONCLUSIONS: Our findings indicate that a substantial proportion of local IDU engage in assisted injecting in outdoor settings and that the practice is associated with other markers of drug-related harm, including being female, daily cocaine injecting and sex trade involvement. These findings suggest that novel interventions are needed to address the needs of this subpopulation of IDU. PMID- 20302637 TI - Antimicrobial peptide-like genes in Nasonia vitripennis: a genomic perspective. AB - BACKGROUND: Antimicrobial peptides (AMPs) are an essential component of innate immunity which can rapidly respond to diverse microbial pathogens. Insects, as a rich source of AMPs, attract great attention of scientists in both understanding of the basic biology of the immune system and searching molecular templates for anti-infective drug design. Despite a large number of AMPs have been identified from different insect species, little information in terms of these peptides is available from parasitic insects. RESULTS: By using integrated computational approaches to systemically mining the Hymenopteran parasitic wasp Nasonia vitripennis genome, we establish the first AMP repertoire whose members exhibit extensive sequence and structural diversity and can be distinguished into multiple molecular types, including insect and fungal defensin-like peptides (DLPs) with the cysteine-stabilized alpha-helical and beta-sheet (CSalphabeta) fold; Pro- or Gly-rich abaecins and hymenoptaecins; horseshoe crab tachystatin type AMPs with the inhibitor cystine knot (ICK) fold; and a linear alpha-helical peptide. Inducible expression pattern of seven N. vitripennis AMP genes were verified, and two representative peptides were synthesized and functionally identified to be antibacterial. In comparison with Apis mellifera (Hymenoptera) and several non-Hymenopteran model insects, N. vitripennis has evolved a complex antimicrobial immune system with more genes and larger protein precursors. Three classical strategies that are likely responsible for the complexity increase have been recognized: 1) Gene duplication; 2) Exon duplication; and 3) Exon-shuffling. CONCLUSION: The present study established the N. vitripennis peptidome associated with antimicrobial immunity by using a combined computational and experimental strategy. As the first AMP repertoire of a parasitic wasp, our results offer a basic platform for further studying the immunological and evolutionary significances of these newly discovered AMP-like genes in this class of insects. PMID- 20302639 TI - Anticentromere antibody positive Sjogren's Syndrome: a retrospective descriptive analysis. AB - INTRODUCTION: A subgroup of patients with primary Sjogren's Syndrome (SS) and positive anticentromere antibodies (ACA) were recognized as having features intermediate between SS and systemic sclerosis (SSc). Our goal was to describe this group clinically and serologically and define its tendency to evolve to full blown SSc. METHODS: Among 535 patients with primary SS we identified 20 ACA positive (ACA+/SS). We compared them to 61 randomly selected ACA negative SS patients (ACA-/SS), 31 ACA positive SSc patients with sicca manifestations [SSc/(+) sicca] and 20 ACA positive SSc patients without sicca manifestations [SSc/(-) sicca]. RESULTS: Prevalence of ACA among SS patients was 3.7%. Cases and controls did not differ in sex ratio and age at disease onset. ACA+/SS patients had a lower prevalence of dry eyes, hypergammaglobulinaemia, anti-Ro and anti-La antibodies and a higher prevalence of Raynaud's phenomenon and dysphagia compared to ACA-/SS patients. They also had lower prevalence of telangiectasias, puffy fingers, sclerodactyly, Raynaud's phenomenon, digital ulcers and gastroesophageal reflux in comparison to both of the SSc subgroups and a lower prevalence of dyspnoea and lung fibrosis compared to the SSc/(+) sicca subgroup. Two patients originally having ACA+/SS evolved to full blown SSc. Four deaths occurred, all among SSc patients. Kaplan Meier analysis showed a significant difference between cases and controls in time from disease onset to development of gastroesophageal reflux, telangiectasias, digital ulcers, arthritis, puffy fingers, xerostomia, hypergammaglobulinaemia and dysphagia. CONCLUSIONS: ACA+/SS has a clinical phenotype intermediate between ACA-/SS and SSc and shows little tendency to evolve to SSc. PMID- 20302640 TI - Early limited nitrosamine exposures exacerbate high fat diet-mediated type 2 diabetes and neurodegeneration. AB - BACKGROUND: Type 2 diabetes mellitus (T2DM) and several types of neurodegeneration, including Alzheimer's, are linked to insulin-resistance, and chronic high dietary fat intake causes T2DM with mild neurodegeneration. Intra cerebral Streptozotocin, a nitrosamine-related compound, causes neurodegeneration, whereas peripheral treatment causes DM. HYPOTHESIS: Limited early exposures to nitrosamines that are widely present in the environment, enhance the deleterious effects of high fat intake in promoting T2DM and neurodegeneration. METHODS: Long Evans rat pups were treated with N nitrosodiethylamine (NDEA) by i.p. injection, and upon weaning, they were fed with high fat (60%; HFD) or low fat (5%; LFD) chow for 8 weeks. Cerebella were harvested to assess gene expression, and insulin and insulin-like growth factor (IGF) deficiency and resistance in the context of neurodegeneration. RESULTS: HFD +/- NDEA caused T2DM, neurodegeneration with impairments in brain insulin, insulin receptor, IGF-2 receptor, or insulin receptor substrate gene expression, and reduced expression of tau and choline acetyltransferase (ChAT), which are regulated by insulin and IGF-1. In addition, increased levels of 4-hydroxynonenal and nitrotyrosine were measured in cerebella of HFD +/- NDEA treated rats, and overall, NDEA+HFD treatment reduced brain levels of Tau, phospho-GSK-3beta (reflecting increased GSK-3beta activity), glial fibrillary acidic protein, and ChAT to greater degrees than either treatment alone. Finally, pro-ceramide genes, examined because ceramides cause insulin resistance, oxidative stress, and neurodegeneration, were significantly up-regulated by HFD and/or NDEA exposure, but the highest levels were generally present in brains of HFD+NDEA treated rats. CONCLUSIONS: Early limited exposure to nitrosamines exacerbates the adverse effects of later chronic high dietary fat intake in promoting T2DM and neurodegeneration. The mechanism involves increased generation of ceramides and probably other toxic lipids in brain. PMID- 20302641 TI - B-lymphocyte stimulator/a proliferation-inducing ligand heterotrimers are elevated in the sera of patients with autoimmune disease and are neutralized by atacicept and B-cell maturation antigen-immunoglobulin. AB - INTRODUCTION: B-lymphocyte stimulator (BLyS) and a proliferation-inducing ligand (APRIL) are members of the tumor necrosis factor (TNF) family that regulate B cell maturation, survival, and function. They are overexpressed in a variety of autoimmune diseases and reportedly exist in vivo not only as homotrimers, but also as BLyS/APRIL heterotrimers. METHODS: A proprietary N-terminal trimerization domain was used to produce recombinant BLyS/APRIL heterotrimers. Heterotrimer biologic activity was compared with that of BLyS and APRIL in a 4-hour signaling assay by using transmembrane activator and CAML interactor (TACI)-transfected Jurkat cells and in a 4-day primary human B-cell proliferation assay. A bead based immunoassay was developed to quantify native heterotrimers in human sera from healthy donors (n = 89) and patients with systemic lupus erythematosus (SLE; n = 89) or rheumatoid arthritis (RA; n = 30). Heterotrimer levels were compared with BLyS and APRIL homotrimer levels in a subset of these samples. RESULTS: The recombinant heterotrimers consisted mostly of one BLyS and two APRIL molecules. Heterotrimer signaling did not show any significant difference compared with APRIL in the TACI-Jurkat assay. Heterotrimers were less-potent inducers of B-cell proliferation than were homotrimeric BLyS or APRIL (EC(50), nMol/L: BLyS, 0.02; APRIL, 0.17; heterotrimers, 4.06). The soluble receptor fusion proteins atacicept and B-cell maturation antigen (BCMA)-immunoglobulin (Ig) neutralized the activity of BLyS, APRIL, and heterotrimers in both cellular assays, whereas B-cell activating factor belonging to the TNF family receptor (BAFF-R)-Ig neutralized only the activity of BLyS. In human sera, significantly more patients with SLE had detectable BLyS (67% versus 18%; P < 0.0001), APRIL (38% versus 3%; P < 0.0002), and heterotrimer (27% versus 8%; P = 0.0013) levels compared with healthy donors. Significantly more patients with RA had detectable APRIL, but not BLyS or heterotrimer, levels compared with healthy donors (83% versus 3%; P < 0.0001). Heterotrimer levels weakly correlated with BLyS, but not APRIL, levels. CONCLUSIONS: Recombinant BLyS/APRIL heterotrimers have biologic activity and are inhibited by atacicept and BCMA-Ig, but not by BAFF-R-Ig. A novel immunoassay demonstrated that native BLyS/APRIL heterotrimers, as well as BLyS and APRIL homotrimers, are elevated in patients with autoimmune diseases. PMID- 20302642 TI - Uses, traditional management, perception of variation and preferences in ackee (Blighia sapida K.D. Koenig) fruit traits in Benin: implications for domestication and conservation. AB - BACKGROUND: Blighia sapida is a woody perennial multipurpose fruit tree species native to the Guinean forests of West Africa. The fleshy arils of the ripened fruits are edible. Seeds and capsules of the fruits are used for soap-making and all parts of the tree have medicinal properties. Although so far overlooked by researchers in the region, the tree is highly valued by farmers and is an important component of traditional agroforestry systems in Benin. Fresh arils, dried arils and soap are traded in local and regional markets in Benin providing substantial revenues for farmers, especially women. Recently, ackee has emerged as high-priority species for domestication in Benin but information necessary to elaborate a clear domestication strategy is still very sketchy. This study addresses farmers' indigenous knowledge on uses, management and perception of variation of the species among different ethnic groups taking into account also gender differences. METHODS: 240 randomly selected persons (50% women) belonging to five different ethnic groups, 5 women active in the processing of ackee fruits and 6 traditional healers were surveyed with semi-structured interviews. Information collected refer mainly to the motivation of the respondents to conserve ackee trees in their land, the local uses, the perception of variation, the preference in fruits traits, the management practices to improve the production and regenerate ackee. RESULTS: People have different interests on using ackee, variable knowledge on uses and management practices, and have reported nine differentiation criteria mainly related to the fruits. Ackee phenotypes with preferred fruit traits are perceived by local people to be more abundant in managed in-situ and cultivated stands than in unmanaged wild stands, suggesting that traditional management has initiated a domestication process. As many as 22 diseases have been reported to be healed with ackee. In general, indigenous knowledge about ackee varies among ethnic and gender groups. CONCLUSIONS: With the variation observed among ethnic groups and gender groups for indigenous knowledge and preference in fruits traits, a multiple breeding sampling strategy is recommended during germplasm collection and multiplication. This approach will promote sustainable use and conservation of ackee genetic resources. PMID- 20302644 TI - Steroidogenic factor-1 (SF-1) gene mutation as a frequent cause of primary amenorrhea in 46,XY female adolescents with low testosterone concentration. AB - BACKGROUND: Primary amenorrhea due to 46,XY disorders of sex differentiation (DSD) is a frequent reason for consultation in endocrine and gynecology clinics. Among the genetic causes of low-testosterone primary amenorrhea due to 46,XY DSD, SRY gene is reported to be frequently involved, but other genes, such as SF1 and WT1, have never been studied for their prevalence. METHODS: We directly sequenced SRY, SF1 and WT1 genes in 15 adolescent girls with primary amenorrhea, low testosterone concentration, and XY karyotype, to determine the prevalence of mutations. We also analyzed the LH receptor gene in patients with high LH and normal FSH concentrations. RESULTS: Among the 15 adolescents with primary amenorrhea and low testosterone concentration, we identified two new SRY mutations, five new SF1 mutations and one new LH receptor gene mutation. Our study confirms the 10-15% prevalence of SRY mutations and shows the high prevalence (33%) of SF1 abnormalities in primary amenorrhea due to 46,XY DSD with low plasma testosterone concentration. CONCLUSIONS: The genetic analysis of low testosterone primary amenorrhea is complex as several factors may be involved. This work underlines the need to systematically analyze the SF1 sequence in girls with primary amenorrhea due to 46,XY DSD and low testosterone, as well as in newborns with 46,XY DSD. PMID- 20302643 TI - Adhesion of monocytes to type I collagen stimulates an APP-dependent proinflammatory signaling response and release of Abeta1-40. AB - BACKGROUND: Amyloid precursor protein (APP) is a ubiquitously expressed cell surface protein reported to be involved in mediating cell-cell or cell-matrix interactions. Prior work has demonstrated that APP co-localizes with beta1 integrin in different cell types. METHODS: In an effort to determine the function of APP on monocytic lineage cells, in particular, the human monocyte cell line, THP-1, was used to assess the role of APP during adhesion to the extracelluar matrix component type I collagen. RESULTS: Pull-down assays demonstrated that THP 1 adhesion to collagen stimulated a tyrosine kinase-associated signaling response which included subsequent phosphorylation of p38 MAP kinase and increased association of APP with alpha2beta1 integrin, specifically. In addition, cell adhesion was dependent upon APP expression since APP siRNA knockdown attenuated THP-1 adhesion to collagen compared to mock transfected controls. One consequence of the tyrosine kinase-dependent signaling response was increased secretion of interleukin-1beta (IL-1beta) and Abeta1-40 but not the Abeta1-42 fragment of APP. Increased secretion of IL-1beta was dependent upon p38 MAP kinase activity while Abeta1-40 secretion required Src family kinase activity since the specific p38 inhibitor, SB202190, and the Src family kinase inhibitor, PP2, attenuated IL 1beta and Abeta1-40 secretion, respectively. CONCLUSIONS: These data demonstrate that APP is involved in classic integrin-dependent tyrosine kinase-associated adhesion and activation of peripheral monocytic cells. Moreover, divergent APP dependent signaling is required for increased secretion of both IL-1beta and Abeta1-40 as a component of the adhesion-dependent change in phenotype. This suggests that APP may have a broad role in not only mediating cell-matrix adhesion but also in the function of peripheral immune cells. PMID- 20302645 TI - Probing the folding of mini-protein Beta3s by two-dimensional infrared spectroscopy; simulation study. AB - We propose to use infrared coherent two-dimensional correlation spectroscopy (2DCS) to characterize the folding mechanism of the mini-protein Beta3s. In this study Beta3s was folded by molecular dynamics (MD) simulation and intermediate conformational ensembles were identified. The one and two-dimensional correlation spectrum was calculated for the intermediate and native states of the mini protein. A direct structure-spectra relationship was determined by analysis of conformational properties and specific residue contributions. We identified the structural origin of diagonal and off-diagonal peaks in the 2DCS spectra for the native and intermediate conformational ensembles in the folding mechanism. This work supports the implementation of computational techniques in conjunction with experimental 2DCS to study the folding mechanism of proteins. In addition to exploring the folding mechanism the work presented here can be applied in combination with experiment to refine and validate current molecular dynamics force fields.PACS Codes: 87.15.Cc, 87.15.hm, 87.15.hp. PMID- 20302646 TI - No effect of 14 day consumption of whole grain diet compared to refined grain diet on antioxidant measures in healthy, young subjects: a pilot study. AB - BACKGROUND: Epidemiological evidence supports that a diet high in whole grains is associated with lowered risk of chronic diseases included coronary heart disease, obesity, type 2 diabetes, and some types of cancer. One potential mechanism for the protective properties of whole grains is their antioxidant content. The aim of this study was to compare differences in antioxidant measures when subjects consumed either refined or whole grain diets. METHODS: Twenty healthy subjects took part in a randomized, crossover dietary intervention study. Subjects consumed either a refined grain or whole grain diet for 14 days and then the other diet for the next 14 days. Male subjects consumed 8 servings of grains per day and female subjects consumed 6 servings of grains per day. Blood and urine samples were collected at the end of each diet. Antioxidant measures included oxygen radical absorbance capacity (ORAC) in blood, and isoprostanes and thiobarbituric acid reactive substances (TBARS) in urine. RESULTS: The whole grain diet was significantly higher in dietary fiber, vitamin B6, folate, selenium, copper, zinc, iron, magnesium and cystine compared to the refined grain diet. Despite high intakes of whole grains, no significant differences were seen in any of the antioxidant measures between the refined and whole grain diets. CONCLUSIONS: No differences in antioxidant measures were found when subjects consumed whole grain diets compared to refined grain diets. PMID- 20302647 TI - OST-HTH: a novel predicted RNA-binding domain. AB - BACKGROUND: The mechanism by which the arthropod Oskar and vertebrate TDRD5/TDRD7 proteins nucleate or organize structurally related ribonucleoprotein (RNP) complexes, the polar granule and nuage, is poorly understood. Using sequence profile searches we identify a novel domain in these proteins that is widely conserved across eukaryotes and bacteria. RESULTS: Using contextual information from domain architectures, sequence-structure superpositions and available functional information we predict that this domain is likely to adopt the winged helix-turn-helix fold and bind RNA with a potential specificity for dsRNA. We show that in eukaryotes this domain is often combined in the same polypeptide with protein-protein- or lipid- interaction domains that might play a role in anchoring these proteins to specific cytoskeletal structures. CONCLUSIONS: Thus, proteins with this domain might have a key role in the recognition and localization of dsRNA, including miRNAs, rasiRNAs and piRNAs hybridized to their targets. In other cases, this domain is fused to ubiquitin-binding, E3 ligase and ubiquitin-like domains indicating a previously under-appreciated role for ubiquitination in regulating the assembly and stability of nuage-like RNP complexes. Both bacteria and eukaryotes encode a conserved family of proteins that combines this predicted RNA-binding domain with a previously uncharacterized domain (DUF88). We present evidence that it is an RNAse belonging to the superfamily that includes the 5'->3' nucleases, PIN and NYN domains and might be recruited to degrade certain RNAs. PMID- 20302648 TI - A community-based study of hypertension and cardio-metabolic syndrome in semi urban and rural communities in Nigeria. AB - BACKGROUND: The prevalence of cardio-metabolic syndrome (CMS) is increasing worldwide. In people of African descent, there is higher prevalence of hypertension and complications than other races. Bearing in mind these facts, we looked at the CMS in the general population and the population with hypertension. Using the new International Diabetes Federation (IDF) definitions of CMS, we studied its prevalence in semi-urban and rural communities in South-east Nigeria in relation to hypertension. METHOD: This is a cross sectional population based study involving 1458 adults aged from 25 to 64 years. Diagnosis of CMS was based on the new IDF criteria using the anthropometric measurements for Europids as there is none yet for blacks. Hypertension was defined according to the WHO/ISH criteria. RESULTS: The overall prevalence of CMS was 18.0% in the semi-urban community as against 10.0% in the rural community increasing to 34.7% and 24.7% respectively in the population with hypertension. The prevalence of co morbidities - hyperglycaemia, abdominal obesity, and hypertriglceridaemia were 13.9%, 41.1% and 23.9% while in the hypertensive populations they were 21.2%, 55.0% and 31.3% in the general population in both communities combined. Except for low HDL cholesterol, every other co-morbidity was higher in hypertensive population than the general population. CONCLUSION: The high prevalence of CMS in the semi-urban population especially for the population with hypertension underscores the double burden of disease in developing countries. The lesson is while infections and infestations are being tackled in these countries the non communicable diseases should not be neglected. PMID- 20302649 TI - Clients of sex workers in Switzerland: it makes sense to counsel and propose rapid test for HIV on the street, a preliminary report. AB - BACKGROUND: Clients of street sex workers may be at higher risk for HIV infection than the general population. Furthermore, there is a lack of knowledge regarding HIV testing of clients of sex workers in developed countries. METHOD: This pilot study assessed the feasibility and acceptance of rapid HIV testing by the clients of street-based sex workers in Lausanne, Switzerland. For 5 evenings, clients in cars were stopped by trained field staff for face-to-face interviews focusing on sex-related HIV risk behaviors and HIV testing history. The clients were then offered a free anonymous rapid HIV test in a bus parked nearby. Rapid HIV testing and counselling were performed by experienced nurse practitioners. Clients with reactive tests were offered confirmatory testing, medical evaluation, and care in our HIV clinic. RESULT: We intercepted 144 men, 112 (77.8%) agreed to be interviewed. Among them, 50 (46.6%) had never been tested for HIV. A total of 31 (27.7%) rapid HIV tests were performed, 16 (51.6%) in clients who had not previously been tested. None were reactive. Initially, 19 (16.9%) additional clients agreed to HIV testing but later declined due to the 40-minute queue for testing. CONCLUSION: This pilot study showed that rapid HIV testing in the red light district of Lausanne was feasible, and that the clients of sex workers accepted testing at an unexpectedly high rate. This setting seems particularly appropriate for targeted HIV screening, since more than 40% of the clients had not previously been tested for HIV even though they engaged in sex-related HIV risk behaviour. PMID- 20302650 TI - Prenatal exposure to serotonin reuptake inhibitors: a case report. AB - Two premature twins (33 weeks gestation) were born to a woman who had used paroxetine during pregnancy for an anxiety-depression disorder. They were admitted to the NICU, where they showed prolonged RDS, cardiovascular malformations, and facial dysmorphisms. Soon after birth, they also presented abnormal neurobehavioral and motor signs, which partially disappeared during the following weeks, although alterations of tone persisted even at discharge. Selective serotonin reuptake inhibitor (SSRI) antidepressants are considered the primary treatments for depression and anxiety in pregnancy. Since intrauterine exposure to these drugs has been associated with poor neonatal adaptation, low birth weight, RDS, neurobehavioural symptoms, and potential teratogenic effects, further studies are needed to assess risks and mechanism of action of SSRIs. Meanwhile, it is advisable to evaluate for each patient the real risk/benefit ratio of continuing or suspending treatment during pregnancy. PMID- 20302651 TI - Prevalence of inflammatory bowel disease in two districts of Sri Lanka: a hospital based survey. AB - BACKGROUND: Inflammatory bowel disease (IBD) is being increasingly diagnosed in Asia. However there are few epidemiological data from the region. METHODS: To determine prevalence and clinical characteristics of IBD, a hospital-based survey was performed in the Colombo and Gampaha districts (combined population 4.5 million) in Sri Lanka. Patients with established ulcerative colitis (UC) and Crohn's disease (CD), who were permanent residents of these adjoining districts, were recruited from hospital registries and out-patient clinics. Clinical information was obtained from medical records and patient interviews. RESULTS: There were 295 cases of IBD (UC = 240, CD = 55), of which 34 (UC = 30, CD = 4) were newly diagnosed during the study year. The prevalence rate for UC was 5.3/100,000 (95% CI 5.0-5.6/100,000), and CD was 1.2/100,000 (95% CI 1.0 1.4/100,000). The incidence rates were 0.69/100,000 (95% CI 0.44-0.94/100,000) for UC and 0.09/100,000 (95% CI 0.002-0.18/100,000) for CD. Female:male ratios were 1.5 for UC and 1.0 for CD. Mean age at diagnosis was (males and females) 36.6 and 38.1y for UC and 33.4 and 36.2y for CD. Among UC patients, 51.1% had proctitis and at presentation 58.4% had mild disease. 80% of CD patients had only large bowel involvement. Few patients had undergone surgery. CONCLUSIONS: The prevalence of IBD in this population was low compared to Western populations, but similar to some in Asia. There was a female preponderance for UC. UC was mainly mild, distal or left-sided, while CD mainly involved the large bowel. PMID- 20302652 TI - Effects of external irradiation of the neck region on intima media thickness of the common carotid artery. AB - BACKGROUND: Several studies have shown that common carotid intima-media thickness (IMT) is increased after radiotherapy (RT) to the head and neck. However, further studies are needed to define the exact mechanism of radiation-induced injury in large vessels, investigate the relationship between radiation dose and large vessel injury and evaluate the rate of progress of atherosclerosis in irradiated vessels. OBJECTIVES: To investigate whether external irradiation to the carotid area has any effect on IMT of the common carotid artery in a group of patients who received RT vs control group matched for age, gender and race. METHODS: We studied 19 patients (10 male; 47.8 +/- 17.4 years) during a 5-month period (January 2009-July 2009); they had completed RT with a mean of 2.9 years before (range: 1 month-6 years) The mean radiation dose to the neck in the irradiated patients was 41.2 +/- 15.6 Gy (range: 25-70 Gy). Common carotid IMT was measured with echo-color Doppler. Nineteen healthy adult patients (10 male; 47.8 +/- 17.6) were recruited as a control group. RESULTS: IMT was not significantly higher in patients when compared to the control group (0.59 +/- 0.16 vs 0.56 +/- 0.16 mm, p = 0.4). There was no significant difference between the two groups in relation to the absence (p = 0.7) or presence (p = 0.6) of vascular risk factors. Although the difference did not reach statistical significance (p = 0.1), the irradiated young patients (age < or = 52 years) had IMT measurements higher (0.54 +/- 0.08 mm) than the non-irradiated young patients (0.49 +/- 0.14 mm). The mean carotid IMT increased with increasing doses of radiation to the neck (p = 0.04). CONCLUSION: This study shows that increased IMT of the common carotid artery after RT is radiation-dose-related. Therefore it is important to monitor IMT, which can be used as an imaging biomarker for early diagnosis of cerebrovascular disease in patients who have had radiotherapy for treatment of cancer of the head and neck and who are at increased risk for accelerated atherosclerosis in carotid arteries. PMID- 20302653 TI - Donor-host mitochondrial compatibility improves efficiency of bovine somatic cell nuclear transfer. AB - BACKGROUND: The interaction between the karyoplast and cytoplast plays an important role in the efficiency of somatic cell nuclear transfer (SCNT), but the underlying mechanism remains unclear. It is generally accepted that in nuclear transfer embryos, the reprogramming of gene expression is induced by epigenetic mechanisms and does not involve modifications of DNA sequences. In cattle, oocytes with various mitochondrial DNA (mtDNA) haplotypes usually have different ATP content and can further affect the efficiency of in vitro production of embryos. As mtDNA comes from the recipient oocyte during SCNT and is regulated by genes in the donor nucleus, it is a perfect model to investigate the interaction between donor nuclei and host oocytes in SCNT. RESULTS: We investigated whether the in vitro development of reconstructed bovine embryos produced by SCNT would be influenced by mtDNA haplotype compatibility between the oocytes and donor cells. Embryos from homotype A-A or B-B showed significantly higher developmental ability at blastocyst stages than the heterotype A-B or B-A combinations. Post implantation development ability, pregnancy rate up to day 90 of gestation, as well as percent of term births were higher in the homotype SCNT groups than in the heterotype groups. In addition, homotype and heterotype SCNT embryos showed different methylation patterns of histone 3-lysine 9 (H3K9) genome-wide and at pluripotency-related genes (Oct-4, Sox-2, Nanog). CONCLUSION: Both histone and DNA methylation show that homotype SCNT blastocysts have a more successful epigenetic asymmetry pattern than heterotype SCNT blastocysts, which indicates more complete nuclear reprogramming. This may result from variability in their epigenetic patterns and responses to nuclear reprogramming. This suggests that the compatibility of mtDNA haplotypes between donor cells and host oocytes can significantly affect the developmental competence of reconstructed embryos in SCNT, and may include an epigenetic mechanism. PMID- 20302654 TI - Genotypes and haplotypes in the insulin-like growth factors, their receptors and binding proteins in relation to plasma metabolic levels and mammographic density. AB - BACKGROUND: Increased mammographic density is one of the strongest independent risk factors for breast cancer. It is believed that one third of breast cancers are derived from breasts with more than 50% density. Mammographic density is affected by age, BMI, parity, and genetic predisposition. It is also greatly influenced by hormonal and growth factor changes in a woman's life cycle, spanning from puberty through adult to menopause. Genetic variations in genes coding for hormones and growth factors involved in development of the breast are therefore of great interest. The associations between genetic polymorphisms in genes from the IGF pathway on mammographic density and circulating levels of IGF1, its binding protein IGFBP3, and their ratio in postmenopausal women are reported here. METHODS: Samples from 964 postmenopausal Norwegian women aged 55 71 years were collected as a part of the Tromso Mammography and Breast Cancer Study. All samples were genotyped for 25 SNPs in IGF1, IGF2, IGF1R, IGF2R, IGFALS and IGFBP3 using Taqman (ABI). The main statistical analyses were conducted with the PROC HAPLOTYPE procedure within SAS/GENETICS (SAS 9.1.3). RESULTS: The haplotype analysis revealed six haploblocks within the studied genes. Of those, four had significant associations with circulating levels of IGF1 or IGFBP3 and/or mammographic density. One haplotype variant in the IGF1 gene was found to be associated with mammographic density. Within the IGF2 gene one haplotype variant was associated with levels of both IGF1 and IGFBP3. Two haplotype variants in the IGF2R were associated with the level of IGF1. Both variants of the IGFBP3 haplotype were associated with the IGFBP3 level and indicate regulation in cis. CONCLUSION: Polymorphisms within the IGF1 gene and related genes were associated with plasma levels of IGF1, IGFBP3 and mammographic density in this study of postmenopausal women. PMID- 20302655 TI - Epidermal growth factor receptor regulates beta-catenin location, stability, and transcriptional activity in oral cancer. AB - BACKGROUND: Many cancerous cells accumulate beta-catenin in the nucleus. We examined the role of epidermal growth factor receptor (EGFR) signaling in the accumulation of beta-catenin in the nuclei of oral cancer cells. RESULTS: We used two strains of cultured oral cancer cells, one with reduced EGFR expression (OECM1 cells) and one with elevated EGFR expression (SAS cells), and measured downstream effects, such as phosphorylation of beta-catenin and GSK-3beta, association of beta-catenin with E-cadherin, and target gene regulation. We also studied the expression of EGFR, beta-catenin, and cyclin D1 in 112 samples of oral cancer by immunostaining. Activation of EGFR signaling increased the amount of beta-catenin in the nucleus and decreased the amount in the membranes. EGF treatment increased phosphorylation of beta-catenin (tyrosine) and GSK-3beta(Ser (9), resulting in a loss of beta-catenin association with E-cadherin. TOP-FLASH and FOP-FLASH reporter assays demonstrated that the EGFR signal regulates beta catenin transcriptional activity and mediates cyclin D1 expression. Chromatin immunoprecipitation experiments indicated that the EGFR signal affects chromatin architecture at the regulatory element of cyclin D1, and that the CBP, HDAC1, and Suv39h1 histone/chromatin remodeling complex is involved in this process. Immunostaining showed a significant association between EGFR expression and aberrant accumulation of beta-catenin in oral cancer. CONCLUSIONS: EGFR signaling regulates beta-catenin localization and stability, target gene expression, and tumor progression in oral cancer. Moreover, our data suggest that aberrant accumulation of beta-catenin under EGFR activation is a malignancy marker of oral cancer. PMID- 20302656 TI - Histone deacetylase inhibitor, butyrate, attenuates lipopolysaccharide-induced acute lung injury in mice. AB - BACKGROUND: Histone deacetylase (HDAC) inhibitors, developed as promising anti tumor drugs, exhibit their anti-inflammatory properties due to their effects on reduction of inflammatory cytokines. OBJECTIVE: To investigate the protective effect of butyrate, a HDAC inhibitor, on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice. METHODS: ALI was induced in Balb/c mice by intratracheally instillation of LPS (1 mg/kg). Before 1 hour of LPS administration, the mice received butyrate (10 mg/kg) orally. The animals in each group were sacrificed at different time point after LPS administration. Pulmonary histological changes were evaluated by hematoxylin-eosin stain and lung wet/dry weight ratios were observed. Concentrations of interleukin (IL)-1beta and tumor necrosis factor (TNF)-alpha in bronchoalveolar lavage fluid (BALF) and concentrations of nitric oxide (NO) and myeloperoxidase (MPO) activity in lung tissue homogenates were measured by enzyme-linked immunosorbent assay (ELISA). Expression of nuclear factor (NF)-kappaB p65 in cytoplasm and nucleus was determined by Western blot analysis respectively. RESULTS: Pretreatment with butyrate led to significant attenuation of LPS induced evident lung histopathological changes, alveolar hemorrhage, and neutrophils infiltration with evidence of reduced MPO activity. The lung wet/dry weight ratios, as an index of lung edema, were reduced by butyrate administration. Butyrate also repressed the production of TNF-alpha, IL-1beta and NO. Furthermore, the expression of NF kappaB p65 in nucleus was markedly suppressed by butyrate pretreatment. CONCLUSIONS: Butyrate had a protective effect on LPS-induced ALI, which may be related to its effect on suppression of inflammatory cytokines production and NF kappaB activation. PMID- 20302657 TI - Role of interferon-gamma release assays in the diagnosis of pulmonary tuberculosis in patients with advanced HIV infection. AB - BACKGROUND: T-cell interferon-gamma release assays (IGRAs) may have a role in the diagnosis of active tuberculosis when evaluating patients for whom standard microbiology has limited sensitivity. Our objective was to examine the accuracy of a commercial IGRA for diagnosis of active tuberculosis in HIV-infected persons. METHODS: We enrolled HIV-infected patients admitted to Mulago Hospital in Kampala, Uganda with cough > or = 2 weeks. All patients underwent standard medical evaluation. We collected peripheral blood specimens at enrollment and performed a commercial, ELISPOT-based IGRA according to the manufacturer's recommendations. IGRA sensitivity and specificity were determined using mycobacterial culture results as the reference standard. RESULTS: Overall, 236 patients were enrolled. The median CD4+ T-lymphocyte count was 49 cells/microl and 126 (53%) patients were diagnosed with active pulmonary tuberculosis. IGRAs were not performed in 24 (10%) patients due to insufficient mononuclear cell counts. In the remaining 212 patients, results were indeterminate in 54 (25%). IGRAs were positive in 95 of 158 (60%) patients with interpretable results. The proportion of positive test results was similar across CD4+ count strata. IGRA sensitivity was 73% and specificity 54%. IGRA results did not meaningfully alter the probability of active tuberculosis in patients with negative sputum smears. CONCLUSIONS: An ELISPOT-based IGRA detected a high prevalence of latent tuberculosis infection in a hospitalized population of tuberculosis suspects with advanced HIV/AIDS but had limited utility for diagnosis of active tuberculosis in a high prevalence setting. Further research is needed to identify stronger and more specific immune responses in patients with active tuberculosis. PMID- 20302658 TI - Nitroprusside modulates pulmonary vein arrhythmogenic activity. AB - BACKGROUND: Pulmonary veins (PVs) are the most important sources of ectopic beats with the initiation of paroxysmal atrial fibrillation, or the foci of ectopic atrial tachycardia and focal atrial fibrillation. Elimination of nitric oxide (NO) enhances cardiac triggered activity, and NO can decrease PV arrhythmogenesis through mechano-electrical feedback. However, it is not clear whether NO may have direct electrophysiological effects on PV cardiomyocytes. This study is aimed to study the effects of nitroprusside (NO donor), on the ionic currents and arrhythmogenic activity of single cardiomyocytes from the PVs. METHODS: Single PV cardiomyocytes were isolated from the canine PVs. The action potential and ionic currents were investigated in isolated single canine PV cardiomyocytes before and after sodium nitroprusside (80 muM,) using the whole-cell patch clamp technique. RESULTS: Nitroprusside decreased PV cardiomyocytes spontaneous beating rates from 1.7 +/- 0.3 Hz to 0.5 +/- 0.4 Hz in 9 cells (P < 0.05); suppressed delayed after depolarization in 4 (80%) of 5 PV cardiomyocytes. Nitroprusside inhibited L-type calcium currents, transient outward currents and transient inward current, but increased delayed rectified potassium currents. CONCLUSION: Nitroprusside regulates the electrical activity of PV cardiomyocytes, which suggests that NO may play a role in PV arrhythmogenesis. PMID- 20302659 TI - Yeast functional screen to identify genetic determinants capable of conferring abiotic stress tolerance in Jatropha curcas. AB - BACKGROUND: Environmentally inflicted stresses such as salinity and drought limit the plant productivity both in natural and agricultural system. Increasing emphasis has been directed to molecular breeding strategies to enhance the intrinsic ability of plant to survive stress conditions. Functional screens in microorganisms with heterologous genes are a rapid, effective and powerful tool to identify stress tolerant genes in plants. Jatropha curcas (Physic nut) has been identified as a potential source of biodiesel plant. In order to improve its productivity under stress conditions to benefit commercial plantations, we initiated prospecting of novel genes expressed during stress in J. curcas that can be utilized to enhance stress tolerance ability of plant. RESULTS: To identify genes expressed during salt tolerance, cDNA expression libraries were constructed from salt-stressed roots of J. curcas, regulated under the control of the yeast GAL1 system. Using a replica based screening, twenty thousand yeast transformants were screened to identify transformants expressing heterologous gene sequences from J. curcas with enhanced ability to tolerate stress. From the screen we obtained 32 full length genes from J. curcas [GenBank accession numbers FJ489601-FJ489611, FJ619041-FJ619057 and FJ623457-FJ623460] that can confer abiotic stress tolerance. As a part of this screen, we optimized conditions for salt stress in J. curcas, defined parameters for salt stress in yeast, as well as isolated three salt hypersensitive yeast strains shs-2, shs-6 and shs-8 generated through a process of random mutagenesis, and exhibited growth retardation beyond 750 mM NaCl. Further, we demonstrated complementation of the salt sensitive phenotypes in the shs mutants, and analyzed the expression patterns for selected J. curcas genes obtained from the screen in both leaf and root tissues after salt stress treatments. CONCLUSIONS: The approach described in this report provides a rapid and universal assay system for large scale screening of genes for varied abiotic stress tolerance within a short span of time. Using this screening strategy we could isolate both genes with previously known function in stress tolerance as well as novel sequences with yet unknown function in salt stress tolerance from J. curcas. The isolated genes could be over-expressed using plant expression system to generate and evaluate transgenic plants for stress tolerance as well as be used as markers for breeding salt stress tolerance in plants. PMID- 20302660 TI - Single feature polymorphism (SFP)-based selective sweep identification and association mapping of growth-related metabolic traits in Arabidopsis thaliana. AB - BACKGROUND: Natural accessions of Arabidopsis thaliana are characterized by a high level of phenotypic variation that can be used to investigate the extent and mode of selection on the primary metabolic traits. A collection of 54 A. thaliana natural accession-derived lines were subjected to deep genotyping through Single Feature Polymorphism (SFP) detection via genomic DNA hybridization to Arabidopsis Tiling 1.0 Arrays for the detection of selective sweeps, and identification of associations between sweep regions and growth-related metabolic traits. RESULTS: A total of 1,072,557 high-quality SFPs were detected and indications for 3,943 deletions and 1,007 duplications were obtained. A significantly lower than expected SFP frequency was observed in protein-, rRNA-, and tRNA-coding regions and in non-repetitive intergenic regions, while pseudogenes, transposons, and non coding RNA genes are enriched with SFPs. Gene families involved in plant defence or in signalling were identified as highly polymorphic, while several other families including transcription factors are depleted of SFPs. 198 significant associations between metabolic genes and 9 metabolic and growth-related phenotypic traits were detected with annotation hinting at the nature of the relationship. Five significant selective sweep regions were also detected of which one associated significantly with a metabolic trait. CONCLUSIONS: We generated a high density polymorphism map for 54 A. thaliana accessions that highlights the variability of resistance genes across geographic ranges and used it to identify selective sweeps and associations between metabolic genes and metabolic phenotypes. Several associations show a clear biological relationship, while many remain requiring further investigation. PMID- 20302661 TI - Exploring cross-sectional associations between common childhood illness, housing and social conditions in remote Australian Aboriginal communities. AB - BACKGROUND: There is limited epidemiological research that provides insight into the complex web of causative and moderating factors that links housing conditions to a variety of poor health outcomes. This study explores the relationship between housing conditions (with a primary focus on the functional state of infrastructure) and common childhood illness in remote Australian Aboriginal communities for the purpose of informing development of housing interventions to improve child health. METHODS: Hierarchical multi-level analysis of association between carer report of common childhood illnesses and functional and hygienic state of housing infrastructure, socio-economic, psychosocial and health related behaviours using baseline survey data from a housing intervention study. RESULTS: Multivariate analysis showed a strong independent association between report of respiratory infection and overall functional condition of the house (Odds Ratio (OR) 3.00; 95%CI 1.36-6.63), but no significant association between report of other illnesses and the overall functional condition or the functional condition of infrastructure required for specific healthy living practices. Associations between report of child illness and secondary explanatory variables which showed an OR of 2 or more included: for skin infection--evidence of poor temperature control in the house (OR 3.25; 95%CI 1.06-9.94), evidence of pests and vermin in the house (OR 2.88; 95%CI 1.25-6.60); for respiratory infection--breastfeeding in infancy (OR 0.27; 95%CI 0.14-0.49); for diarrhoea/vomiting--hygienic state of food preparation and storage areas (OR 2.10; 95%CI 1.10-4.00); for ear infection- child care attendance (OR 2.25; 95%CI 1.26-3.99). CONCLUSION: These findings add to other evidence that building programs need to be supported by a range of other social and behavioural interventions for potential health gains to be more fully realised. PMID- 20302662 TI - Psychometric evaluation of a radio electric auricular treatment for stress related disorders: a double-blinded, placebo-controlled controlled pilot study. AB - BACKGROUND: The aim of this double-blind randomized study is to test the efficacy of a radio electric stimulator device using an auricular reflex therapy protocol for stress-related symptoms. METHODS: The study has been carried out on 200 subjects (138 females, 62 males) that voluntarily came to our Institute declaring to "feel stressed".The participants were randomly allocated with a computerized procedure: 150 were treated with auricular therapeutic protocol with radio electric stimulator device (REAC) and 50 were treated with an inactivated, placebo REAC. Psychological stress was evaluated trough the self-administered questionnaire Psychological Stress Measure (PSM). Assessment data were collected at 2 time points: before the treatment (T0) and immediately after the therapy cycle of 18 sessions about 4 weeks later (T1). RESULTS: In the group treated with REAC, the psychometric evaluation after the therapy's cycle showed a significant reduction of PSM total scores, from 107.8 +/- 23,13 at T0 to 87.1 +/- 16,21 at T1 (p < 0.5), while in the control group no significant variation in decreasing stress-related symptomatology has been noted (107.86 +/- 25,80 at T0 and 106.32 +/- 25,88 at T1 (p = NS). CONCLUSIONS: The protocol of the auricular treatment with REAC seems to reduce the subjective perception of stress, as "psychometrically" demonstrated by the significant reduction in PSM test total score. This therapeutical procedure also provides a non invasive, not painful and very simple innovative approach to treat the widely diffused stress related disorders. TRIAL REGISTRATION: This trial has been registered in the Australian New Zealand Clinical Trials Registry (ANZCTR) with the number: ACTRN12607000529448. PMID- 20302664 TI - LCP external fixation--external application of an internal fixator: two cases and a review of the literature. AB - The locking compression plate (LCP) is an angle-stable fixator intended for intracorporeal application. In selected cases, it can be applied externally in an extracorporeal location to function as a monolateral external fixator. We describe one patient with Schatzker V tibial plateau fracture and one patient with Gustillo IIIB open tibia shaft fracture treated initially with traditional external fixation for whom exchange fixation with externally applied LCPs was performed. The first case went on to bony union while the second case required bone grafting for delayed union. Both patients found that the LCP external fixators facilitated mobilization and were more manageable and aesthetically acceptable than traditional bar-Schanz pin fixators. PMID- 20302663 TI - A prostacyclin analogue, iloprost, protects from bleomycin-induced pulmonary fibrosis in mice. AB - BACKGROUND: Metabolites of arachidonic acid such as prostacyclin (PGI2) have been shown to participate in the pathogenesis of pulmonary fibrosis by inhibiting the expression of pro-inflammatory and pro-fibrotic mediators. In this investigation, we examined whether iloprost, a stable PGI2 analogue, could prevent bleomycin induced pulmonary inflammation and fibrosis in a mouse model. METHODS: Mice received a single intratracheal injection of bleomycin with or without intraperitoneal iloprost. Pulmonary inflammation and fibrosis were analysed by histological evaluation, cellular composition of bronchoalveolar lavage (BAL) fluid, and hydroxyproline content. Lung mechanics were measured. We also analysed the expression of inflammatory mediators in BAL fluid and lung tissue. RESULTS: Administration of iloprost significantly improved survival rate and reduced weight loss in the mice induced by bleomycin. The severe inflammatory response and fibrotic changes were significantly attenuated in the mice treated with iloprost as shown by reduction in infiltration of inflammatory cells into the airways and pulmonary parenchyma, diminution in interstitial collagen deposition, and lung hydroxyproline content. Iloprost significantly improved lung static compliance and tissue elastance. It increased the expression of IFNgamma and CXCL10 in lung tissue measured by RT-PCR and their levels in BAL fluid as measured by ELISA. Levels of TNFalpha, IL-6 and TGFbeta1 were lowered by iloprost. CONCLUSIONS: Iloprost prevents bleomycin-induced pulmonary fibrosis, possibly by upregulating antifibrotic mediators (IFNgamma and CXCL10) and downregulating pro-inflammatory and pro-fibrotic cytokines (TNFalpha, IL-6, and TGFbeta1). Prostacyclin may represent a novel pharmacological agent for treating pulmonary fibrotic diseases. PMID- 20302665 TI - Distinguishing between hot-spots and melting-pots of genetic diversity using haplotype connectivity. AB - We introduce a method to help identify how the genetic diversity of a species within a geographic region might have arisen. This problem appears, for example, in the context of identifying refugia in phylogeography, and in the conservation of biodiversity where it is a factor in nature reserve selection. Complementing current methods for measuring genetic diversity, we analyze pairwise distances between the haplotypes of a species found in a geographic region and derive a quantity, called haplotype connectivity, that aims to capture how divergent the haplotypes are relative to one another. We propose using haplotype connectivity to indicate whether, for geographic regions that harbor a highly diverse collection of haplotypes, diversity evolved inside a region over a long period of time (a "hot-spot") or is the result of a more recent mixture (a "melting-pot"). We describe how the haplotype connectivity for a collection of haplotypes can be computed efficiently and briefly discuss some related optimization problems that arise in this context. We illustrate the applicability of our method using two previously published data sets of a species of beetle from the genus Brachyderes and a species of tree from the genus Pinus. PMID- 20302666 TI - Library of molecular associations: curating the complex molecular basis of liver diseases. AB - BACKGROUND: Systems biology approaches offer novel insights into the development of chronic liver diseases. Current genomic databases supporting systems biology analyses are mostly based on microarray data. Although these data often cover genome wide expression, the validity of single microarray experiments remains questionable. However, for systems biology approaches addressing the interactions of molecular networks comprehensive but also highly validated data are necessary. RESULTS: We have therefore generated the first comprehensive database for published molecular associations in human liver diseases. It is based on PubMed published abstracts and aimed to close the gap between genome wide coverage of low validity from microarray data and individual highly validated data from PubMed. After an initial text mining process, the extracted abstracts were all manually validated to confirm content and potential genetic associations and may therefore be highly trusted. All data were stored in a publicly available database, Library of Molecular Associations http://www.medicalgenomics.org/databases/loma/news, currently holding approximately 1260 confirmed molecular associations for chronic liver diseases such as HCC, CCC, liver fibrosis, NASH/fatty liver disease, AIH, PBC, and PSC. We furthermore transformed these data into a powerful resource for molecular liver research by connecting them to multiple biomedical information resources. CONCLUSION: Together, this database is the first available database providing a comprehensive view and analysis options for published molecular associations on multiple liver diseases. PMID- 20302667 TI - Management of giant pseudomeningoceles after spinal surgery. AB - BACKGROUND: Pseudomeningoceles are a rare complication after spinal surgery, and studies on these complex formations are few. METHODS: Between October 2000 and March 2008, 11 patients who developed symptomatic pseudomeningoceles after spinal surgery were recruited. In this retrospective study, we reported our experiences in the management of these complex, symptomatic pseudomeningoceles after spinal surgery. A giant pseudomeningocele was defined as a pseudomeningocele >8 cm in length. We also evaluated the risk factors for the formation of giant pseudomeningoceles. RESULTS: All patients were treated successfully with a combined treatment protocol of open revision surgery for extirpation of the pseudomeningoceles, repair of dural tears, and implantation of a subarachnoid catheter for drainage. Surgery-related complications were not observed. Recurrence of pseudomeningocele was not observed for any patient at a mean follow up of 16.5 months. This result was confirmed by magnetic resonance imaging. CONCLUSIONS: We conclude that a combined treatment protocol involving open revision surgery for extirpation of pseudomeningoceles, repair of dural tears, and implantation of a subarachnoid catheter for drainage is safe and effective to treat giant pseudomeningoceles. PMID- 20302668 TI - Measuring physical activity among pregnant women using a structured one-week recall questionnaire: evidence for validity and reliability. AB - BACKGROUND: Accurate measurement of the components of physical activity during pregnancy can aid in our understanding of the dose response relationships between physical activity and corresponding perinatal outcomes. The aim of this study was to develop and evaluate a one-week recall questionnaire to assess moderate to vigorous physical activity during pregnancy. METHODS: To assess concurrent related validity, 177 pregnant women (median 18 weeks' gestation, interquartile range (IQR) 15 -23) kept a structured diary and wore an accelerometer (Actigraph) for one week. At the conclusion of the week, they completed the Pregnancy Infection and Nutrition 3 (PIN3) physical activity questionnaire over the telephone. To assess evidence for test-retest reliability, 109 pregnant women (median 19 weeks' gestation, IQR 18-27) completed the questionnaire twice over the telephone, within 48 hours apart, recalling the same two time periods. Spearman correlation coefficients (SCC) and intraclass correlation coefficients (ICC) were used to assess evidence for validity and reliability, respectively. RESULTS: Comparison of the questionnaire to the structured diary was moderate to substantial (SCC 0.47 to 0.69) for several measures of moderate or vigorous physical activity using either perceived or absolute intensity. Comparison of moderate to vigorous physical activity from the questionnaire (absolute intensity using MET-hours/week) to the accelerometer ranged from 0.12 to 0.23 using SCC for absolute intensity (MET-hours/week) and 0.28 to 0.34 using relative intensity (hours/week) (n = 177). Test-retest reliability was moderate to almost perfect for moderate to vigorous physical activity, with the ICC ranging from 0.56 to 0.82 for both perceived and absolute intensities. CONCLUSIONS: The PIN3 one-week recall questionnaire assessed moderate to vigorous physical activity in the past week with evidence for reliability and validity. PMID- 20302669 TI - Patients' knowledge and perception on optic neuritis management before and after an information session. AB - BACKGROUND: Patients' understanding of their condition affect the choice of treatment. The aim of this study is to evaluate patients' understanding and treatment preferences before and after an information session on the treatment of acute optic neuritis. METHODS: Participants were asked to complete a questionnaire consisting of 14 questions before and after an information session presented by a neuro-ophthalmologist. The information session highlighted the treatment options and the treatment effects based on the Optic Neuritis Treatment Trial in plain patient language. The information session stressed the finding that high dose intravenous steroid therapy accelerated visual recovery but does not change final vision and that treatment with oral prednisone alone resulted in a higher incidence of recurrent optic neuritis. RESULTS: Before the information session, 23 (85%) participants knew that there was treatment available for ON and this increased to 27 (100%) after the information session. There were no significantly change in patients knowledge of symptoms of ON and purpose of treatment before and after the information session. Before the information session, 4 (14%) respondents reported they would like to be treated by oral steroid alone in the event of an optic neuritis and 5 (19%) did not respond. After the education session, only 1 patient (4%) indicated they would undergo treatment with oral steroid alone but 25 (92%) indicated they would undergo treatment with intravenous steroid treatment, alone or in combination with oral treatment. Results indicated that there were significant differences in the numbers of participants selecting that they would undergo treatment with a steroid injection (n = 22, p = 0.016). CONCLUSIONS: In this study, patients have shown good understanding of the symptoms and signs of optic neuritis. The finding that significant increases in the likelihood of patients engaging in best practice can be achieved with an information session is very important. This suggests that patient knowledge of available treatments and outcomes can play an important role in implementing and adopting guideline recommendations. PMID- 20302670 TI - Identification and evaluation of new reference genes in Gossypium hirsutum for accurate normalization of real-time quantitative RT-PCR data. AB - BACKGROUND: Normalizing through reference genes, or housekeeping genes, can make more accurate and reliable results from reverse transcription real-time quantitative polymerase chain reaction (qPCR). Recent studies have shown that no single housekeeping gene is universal for all experiments. Thus, suitable reference genes should be the first step of any qPCR analysis. Only a few studies on the identification of housekeeping gene have been carried on plants. Therefore qPCR studies on important crops such as cotton has been hampered by the lack of suitable reference genes. RESULTS: By the use of two distinct algorithms, implemented by geNorm and NormFinder, we have assessed the gene expression of nine candidate reference genes in cotton: GhACT4, GhEF1alpha5, GhFBX6, GhPP2A1, GhMZA, GhPTB, GhGAPC2, GhbetaTUB3 and GhUBQ14. The candidate reference genes were evaluated in 23 experimental samples consisting of six distinct plant organs, eight stages of flower development, four stages of fruit development and in flower verticils. The expression of GhPP2A1 and GhUBQ14 genes were the most stable across all samples and also when distinct plants organs are examined. GhACT4 and GhUBQ14 present more stable expression during flower development, GhACT4 and GhFBX6 in the floral verticils and GhMZA and GhPTB during fruit development. Our analysis provided the most suitable combination of reference genes for each experimental set tested as internal control for reliable qPCR data normalization. In addition, to illustrate the use of cotton reference genes we checked the expression of two cotton MADS-box genes in distinct plant and floral organs and also during flower development. CONCLUSION: We have tested the expression stabilities of nine candidate genes in a set of 23 tissue samples from cotton plants divided into five different experimental sets. As a result of this evaluation, we recommend the use of GhUBQ14 and GhPP2A1 housekeeping genes as superior references for normalization of gene expression measures in different cotton plant organs; GhACT4 and GhUBQ14 for flower development, GhACT4 and GhFBX6 for the floral organs and GhMZA and GhPTB for fruit development. We also provide the primer sequences whose performance in qPCR experiments is demonstrated. These genes will enable more accurate and reliable normalization of qPCR results for gene expression studies in this important crop, the major source of natural fiber and also an important source of edible oil. The use of bona fide reference genes allowed a detailed and accurate characterization of the temporal and spatial expression pattern of two MADS-box genes in cotton. PMID- 20302672 TI - High survival and treatment success sustained after two and three years of first line ART for children in Cambodia. AB - BACKGROUND: Long-term outcomes of antiretroviral therapy (ART) in children remain poorly documented in resource-limited settings. The objective of this study was to assess two-and three-year survival, CD4 evolution and virological response among children on ART in a programmatic setting in Cambodia. METHODS: Children treated with first-line ART for at least 24 months were assessed with viral load testing and genotyping. We used Kaplan-Meier analysis for survival and Cox regression to identify risk factors associated with treatment failure. RESULTS: Of 1168 registered HIV-positive children, 670 (57%) started ART between January 2003 and December 2007. Survival probability was 0.93 (95% CI: 0.91-0.95) and 0.91 (95% CI: 0.88-0.93) at 24 and 36 months after ART initiation, respectively. Median CD4 gain for children aged over five years was 704 cells/mm3 at 24 months and 737 at 36 months. Median CD4 percentage gain for children under five years old was 15.2% at 24 months and 15% at 36 months. One hundred and thirty children completed at least 24 months of ART, and 138 completed 36 months: 128 out of 268 (48%) were female. Median age at ART initiation was six years.Overall, 22 children had viral loads of >1000 copies/ml (success ratio = 86% on intention-to treat-analysis) and 21 of 21 presented mutations conferring resistance mostly to lamivudine and non-nucleoside reverse transcriptase inhibitors. Risk factors for failure after 24 and 36 months were CD4 counts below the threshold for severe immunosupression at those months respectively. Only two out of 22 children with viral loads of >1000 copies/ml met the World Health Organization immunological criteria for failure (sensitivity = 0.1). CONCLUSIONS: Good survival, immunological restoration and viral suppression can be sustained after two to three years of ART among children in resource-constrained settings. Increased access to routine virological measurements is needed for timely diagnosis of treatment failure. PMID- 20302671 TI - Obstacles to researching the researchers: a case study of the ethical challenges of undertaking methodological research investigating the reporting of randomised controlled trials. AB - BACKGROUND: Recent cohort studies of randomised controlled trials have provided evidence of within-study selective reporting bias; where statistically significant outcomes are more likely to be more completely reported compared to non-significant outcomes. Bias resulting from selective reporting can impact on meta-analyses, influencing the conclusions of systematic reviews, and in turn, evidence based clinical practice guidelines.In 2006 we received funding to investigate if there was evidence of within-study selective reporting in a cohort of RCTs submitted to New Zealand Regional Ethics Committees in 1998/99. This research involved accessing ethics applications, their amendments and annual reports, and comparing these with corresponding publications. We did not plan to obtain informed consent from trialists to view their ethics applications for practical and scientific reasons. In November 2006 we sought ethical approval to undertake the research from our institutional ethics committee. The Committee declined our application on the grounds that we were not obtaining informed consent from the trialists to view their ethics application. This initiated a seventeen month process to obtain ethical approval. This publication outlines what we planned to do, the issues we encountered, discusses the legal and ethical issues, and presents some potential solutions. DISCUSSION AND CONCLUSION: Methodological research such as this has the potential for public benefit and there is little or no harm for the participants (trialists) in undertaking it. Further, in New Zealand, there is freedom of information legislation, which in this circumstance, unambiguously provided rights of access and use of the information in the ethics applications. The decision of our institutional ethics committee defeated this right and did not recognise the nature of this observational research. Methodological research, such as this, can be used to develop processes to improve quality in research reporting. Recognition of the potential benefit of this research in the broader research community, and those who sit on ethics committees, is perhaps needed. In addition, changes to the ethical review process which involve separation between those who review proposals to undertake methodological research using ethics applications, and those with responsibility for reviewing ethics applications for trials, should be considered. Finally, we contend that the research community could benefit from quality improvement approaches used in allied sectors. PMID- 20302674 TI - Mapping malaria incidence distribution that accounts for environmental factors in Maputo Province--Mozambique. AB - BACKGROUND: The objective was to study if an association exists between the incidence of malaria and some weather parameters in tropical Maputo province, Mozambique. METHODS: A Bayesian hierarchical model to malaria count data aggregated at district level over a two years period is formulated. This model made it possible to account for spatial area variations. The model was extended to include environmental covariates temperature and rainfall. Study period was then divided into two climate conditions: rainy and dry seasons. The incidences of malaria between the two seasons were compared. Parameter estimation and inference were carried out using MCMC simulation techniques based on Poisson variation. Model comparisons are made using DIC. RESULTS: For winter season, in 2001 the temperature covariate with estimated value of -8.88 shows no association to malaria incidence. In year 2002, the parameter estimation of the same covariate resulted in 5.498 of positive level of association. In both years rainfall covariate determines no dependency to malaria incidence. Malaria transmission is higher in wet season with both covariates positively related to malaria with posterior means 1.99 and 2.83 in year 2001. For 2002 only temperature is associated to malaria incidence with estimated value 2.23. CONCLUSIONS: The incidence of malaria in year 2001, presents an independent spatial pattern for temperature in summer and for rainfall in winter seasons respectively. In year 2002 temperature determines the spatial pattern of malaria incidence in the region. Temperature influences the model in cases where both covariates are introduced in winter and summer season. Its influence is extended to the summer model with temperature covariate only. It is reasonable to state that with the occurrence of high temperatures, malaria incidence had certainly escalated in this year. PMID- 20302673 TI - Anterior cervical discectomy with fusion in patients with cervical disc degeneration: a prospective outcome study of 258 patients (181 fused with autologous bone graft and 77 fused with a PEEK cage). AB - BACKGROUND: Anterior cervical discectomy with fusion (ACDF) is challenging with respect to both patient selection and choice of surgical procedure. The aim of this study was to evaluate the clinical outcome of ACDF, with respect to both patient selection and choice of surgical procedure: fusion with an autologous iliac crest graft (AICG) versus fusion with an artificial cage made of polyetheretherketone (PEEK). METHODS: This was a non-randomized prospective single-center outcome study of 258 patients who underwent ACDF for cervical disc degeneration (CDD). Fusion was attained with either tricortical AICG or PEEK cages without additional anterior plating, with treatment selected at surgeon's discretion. Radicular pain, neck-pain, headache and patient satisfaction with the treatment were scored using the visual analogue scale (VAS). RESULTS: The median age was 47.5 (28.3-82.8) years, and 44% of patients were female. 59% had single level ACDF, 40% had two level ACDF and 1% had three-level ACDF. Of the patients, 181 were fused with AICG and 77 with a PEEK-cage. After surgery, the patients showed a significant reduction in radicular pain (DeltaVAS = 3.05), neck pain (DeltaVAS = 2.30) and headache (DeltaVAS = 0.55). Six months after surgery, 48% of patients had returned to work: however 24% were still receiving workers' compensation.Using univariate and multivariate analyses we found that high preoperative pain intensity was significantly associated with a decrease in pain intensity after surgery, for all three pain categories. There were no significant correlations between pain relief and the following patient characteristics: fusion method (AICG or PEEK-cage), sex, age, number of levels fused, disc level fused, previous neck surgery (except for neck pain), previous neck trauma, or preoperative symptom duration. Two hundred out of the 256 (78%) patients evaluated the surgical result as successful. Only 27/256 (11%) classified the surgical result as a failure. Patient satisfaction was significantly associated with pain relief after surgery. CONCLUSIONS: ACDF is an effective treatment for radicular pain in selected patients with CDD after six months follow up. Because of similar clinical outcomes and lack of donor site morbidity when using PEEK, we now prefer fusion with PEEK cage to AICG. Lengthy symptom duration was not a negative prognostic marker in our patient population. The number of patients who returned to work 6 months after surgery was lower than expected. PMID- 20302675 TI - Case of a sigmoid colon cancer with metachronous metastases to the mesorectum and the abdominal wall. AB - BACKGROUND: Sigmoid colon cancer metachronous metastases commonly occur in the liver and lungs with sporadic reports also to the spleen, stomach, thyroid gland, abdominal wall and upper urinary tract. This is a rare case of metachronous metastases invading the mesorectum and the abdominal wall. CASE PRESENTATION: A 72-year-old female underwent sigmoidectomy for stage I (T2N0 M0) sigmoid colon cancer in May 2008. In June 2009, an abdominal computed tomography scan revealed a tumor 2 cm in size at the lower anterior mesorectum and a second mass 2 cm in size at the anterior abdominal wall midline. Total colonoscopy showed no mucosal lesion. The serum carcinoembryonic antigen level was normal. A biopsy of the mesorectum tumor showed similar histologic characteristics with the primary tumor. Since no other site of recurrence was identified, an abdominoperineal resection was attempted. During the operation and after the removal of the incision recurrence, sinus bradycardia and signs of myocardial ischemia were noticed. A loop transverse colostomy was immediately perfomed and the operation was terminated. Postoperative cardiologic examination revealed an acute myocardium infract. Chemo-radiation of the mesorectum tumor and re-evaluation for surgical excision was decided. CONCLUSION: Metachronous metastasis of the mesorectum from sigmoid colon cancer is extremely rare. Although patterns of lymphatic spread from rectal cancer to sigmoid colon have recently been demonstrated, there is no evidence of metachronous mesorectum invasion from sigmoid colon cancer. This could be the issue for future trials. PMID- 20302676 TI - An R2R3 MYB transcription factor associated with regulation of the anthocyanin biosynthetic pathway in Rosaceae. AB - BACKGROUND: The control of plant anthocyanin accumulation is via transcriptional regulation of the genes encoding the biosynthetic enzymes. A key activator appears to be an R2R3 MYB transcription factor. In apple fruit, skin anthocyanin levels are controlled by a gene called MYBA or MYB1, while the gene determining fruit flesh and foliage anthocyanin has been termed MYB10. In order to further understand tissue-specific anthocyanin regulation we have isolated orthologous MYB genes from all the commercially important rosaceous species. RESULTS: We use gene specific primers to show that the three MYB activators of apple anthocyanin (MYB10/MYB1/MYBA) are likely alleles of each other. MYB transcription factors, with high sequence identity to the apple gene were isolated from across the rosaceous family (e.g. apples, pears, plums, cherries, peaches, raspberries, rose, strawberry). Key identifying amino acid residues were found in both the DNA binding and C-terminal domains of these MYBs. The expression of these MYB10 genes correlates with fruit and flower anthocyanin levels. Their function was tested in tobacco and strawberry. In tobacco, these MYBs were shown to induce the anthocyanin pathway when co-expressed with bHLHs, while over-expression of strawberry and apple genes in the crop of origin elevates anthocyanins. CONCLUSIONS: This family-wide study of rosaceous R2R3 MYBs provides insight into the evolution of this plant trait. It has implications for the development of new coloured fruit and flowers, as well as aiding the understanding of temporal spatial colour change. PMID- 20302678 TI - Protocol for a randomised controlled trial investigating the effectiveness of an online e health application for the prevention of Generalised Anxiety Disorder. AB - BACKGROUND: Generalised Anxiety Disorder (GAD) is a highly prevalent psychiatric disorder. Effective prevention in young adulthood has the potential to reduce the prevalence of the disorder, to reduce disability and lower the costs of the disorder to the community. The present trial (the WebGAD trial) aims to evaluate the effectiveness of an evidence-based online prevention website for GAD. METHODS/DESIGN: The principal clinical question under investigation is the effectiveness of an online GAD intervention (E-couch) using a community-based sample. We examine whether the effect of the intervention can be maximised by either human support, in the form of telephone calls, or by automated support through emails. The primary outcome will be a reduction in symptoms on the GAD-7 in the active arms relative to the non active intervention arms. DISCUSSION: The WebGAD trial will be the first to evaluate the use of an internet-based cognitive behavioural therapy (CBT) program contrasted with a credible control condition for the prevention of GAD and the first formal RCT evaluation of a web-based program for GAD using community recruitment. In general, internet-based CBT programs have been shown to be effective for the treatment of other anxiety disorders such as Post Traumatic Stress Disorder, Social Phobia, Panic Disorder and stress in clinical trials; however there is no evidence for the use of internet CBT in the prevention of GAD. Given the severe shortage of therapists identified in Australia and overseas, and the low rates of treatment seeking in those with a mental illness, the successful implementation of this protocol has important practical outcomes. If found to be effective, WebGAD will provide those experiencing GAD with an easily accessible, free, evidence-based prevention tool which can be promoted and disseminated immediately. PMID- 20302677 TI - A plant natriuretic peptide-like molecule of the pathogen Xanthomonas axonopodis pv. citri causes rapid changes in the proteome of its citrus host. AB - BACKGROUND: Plant natriuretic peptides (PNPs) belong to a novel class of peptidic signaling molecules that share some structural similarity to the N-terminal domain of expansins and affect physiological processes such as water and ion homeostasis at nano-molar concentrations. The citrus pathogen Xanthomonas axonopodis pv. citri possesses a PNP-like peptide (XacPNP) uniquely present in this bacteria. Previously we observed that the expression of XacPNP is induced upon infection and that lesions produced in leaves infected with a XacPNP deletion mutant were more necrotic and lead to earlier bacterial cell death, suggesting that the plant-like bacterial PNP enables the plant pathogen to modify host responses in order to create conditions favorable to its own survival. RESULTS: Here we measured chlorophyll fluorescence parameters and water potential of citrus leaves infiltrated with recombinant purified XacPNP and demonstrate that the peptide improves the physiological conditions of the tissue. Importantly, the proteomic analysis revealed that these responses are mirrored by rapid changes in the host proteome that include the up-regulation of Rubisco activase, ATP synthase CF1 alpha subunit, maturase K, and alpha- and beta tubulin. CONCLUSIONS: We demonstrate that XacPNP induces changes in host photosynthesis at the level of protein expression and in photosynthetic efficiency in particular. Our findings suggest that the biotrophic pathogen can use the plant-like hormone to modulate the host cellular environment and in particular host metabolism and that such modulations weaken host defence. PMID- 20302679 TI - Renal cell cancer without a renal primary. AB - Renal cell carcinoma has been increasing in incidence over the past two decades. Men are affected more than women and metastatic disease at presentation occurs in up to one third of patients. Metastasis can occur to virtually any organ, and involvement of multiple organs is not uncommon. To date, no reports have been found of metastatic disease without a renal primary. We present a case of renal cell cancer initially presenting as a subcutaneous mass with subsequent pancreatic and parotid gland metastases in absence of a primary renal source. PMID- 20302680 TI - Prevalence of various human papillomavirus (HPV) genotypes among women who subjected to routine Pap smear test in Bushehr city (south west of Iran) 2008 2009. AB - BACKGROUND: Some genotypes of human papillomaviruses can infect the genital tract and they are important infectious agents which their oncogenicity is regardable. Thus the aim of this study was to determine the prevalence of various genital human papillomaviruses (HPV) among women being subjected to routine pap smear test in Bushehr city of Iran. RESULTS: Based on the collected data, 11(5.5%) samples were detected positive for HPV DNA and 189(94.5%) samples out of 200 samples were detected negative for HPV DNA. Meanwhile 4(2%) samples detected positive for HPV DNA by PCR were detected positive for HPV by pap smear test as well. On the other hand 5 samples which were detected positive for HPV by pap smear test didn't have HPV DNA after being tested by PCR method. Among the 11 positive samples 7 samples were identified as HPV-16, 3 samples were HPV-18 and one was HPV-53. CONCLUSION: Regarding the prevalence of highly carcinogen genotypes of HPV in our study determination of genital HPV prevalence among the normal population of women of Bushehr city is recommended. PMID- 20302681 TI - Sensitivity of methods for estimating breeding values using genetic markers to the number of QTL and distribution of QTL variance. AB - The objective of this simulation study was to compare the effect of the number of QTL and distribution of QTL variance on the accuracy of breeding values estimated with genomewide markers (MEBV). Three distinct methods were used to calculate MEBV: a Bayesian Method (BM), Least Angle Regression (LARS) and Partial Least Square Regression (PLSR). The accuracy of MEBV calculated with BM and LARS decreased when the number of simulated QTL increased. The accuracy decreased more when QTL had different variance values than when all QTL had an equal variance. The accuracy of MEBV calculated with PLSR was affected neither by the number of QTL nor by the distribution of QTL variance. Additional simulations and analyses showed that these conclusions were not affected by the number of individuals in the training population, by the number of markers and by the heritability of the trait. Results of this study show that the effect of the number of QTL and distribution of QTL variance on the accuracy of MEBV depends on the method that is used to calculate MEBV. PMID- 20302682 TI - Quercetin, the active phenolic component in kiwifruit, prevents hydrogen peroxide induced inhibition of gap-junction intercellular communication. AB - We evaluated the effects of the two main kiwifruit cultivars (gold kiwifruit (GOK) and green kiwifruit (GRK)) and their active phenolic compound, quercetin, on H2O2-induced inhibition of gap-junction intercellular communication (GJIC) in WB-F344 rat liver epithelial cells. We found that both GOK and GRK protect WB F344 cells from H2O2-induced inhibition of GJIC. The extracellular signal regulated protein kinase 1/2 (ERK1/2)-connexin 43 (Cx43) signalling pathway is crucial for the regulation of GJIC, and both GOK and GRK blocked the H2O2-induced phosphorylation of Cx43 and ERK1/2 in WB-F344 cells. Quercetin alone attenuated the H2O2-mediated ERK1/2-Cx43 signalling pathway and consequently reversed H2O2 mediated inhibition of GJIC in WB-F344 cells. A free radical-scavenging assay using 1,1-diphenyl-2-picrylhydrazyl showed that the scavenging activity of quercetin was higher than that of a synthetic antioxidant, butylated hydroxytoluene, per mol, suggesting that the chemopreventive effect of quercetin on H2O2-mediated inhibition of ERK1/2-Cx43 signalling and GJIC may be mediated through its free radical-scavenging activity. Since the carcinogenicity of reactive oxygen species such as H2O2 is attributable to the inhibition of GJIC, GOK, GRK and quercetin may have chemopreventive potential by preventing the inhibition of GJIC. PMID- 20302683 TI - Evaluation of olopatadine hydrochloride nasal spray, 0.6%, used in combination with an intranasal corticosteroid in seasonal allergic rhinitis. AB - The combination of intranasal antihistamines and intranasal corticosteroids results in superior relief of seasonal allergic rhinitis (SAR) symptoms compared with monotherapy. This study was designed to evaluate the safety and efficacy of olopatadine hydrochloride nasal spray, 0.6% (OLO), administered in combination with fluticasone nasal spray, 50 micrograms (FNS), relative to azelastine nasal spray, 0.1% (AZE), administered in combination with FNS in the treatment of SAR. This was a multicenter, double-blind, randomized, parallel-group comparison of OLO + FNS versus AZE + FNS administered for 14 days to patients > or =12 years of age with histories of SAR. Efficacy assessments recorded by patients in a daily diary included nasal symptom scores. Safety was evaluated based on adverse events (AEs). Pretreatment values for reflective total nasal symptoms scores (rTNSS) were similar for both treatment groups. The mean (SD) 2-week average rTNSS was 4.28 (2.63) for OLO + FNS and 4.15 (2.63) for AZE + FNS; these scores were not statistically different between treatment groups. No significant differences (p > 0.05) between OLO + FNS and AZE + FNS were observed for the average 2-week percent changes from baseline in rTNSS or in the individual nasal symptoms (nasal congestion, rhinorrhea, itchy nose, and sneezing). Compared with baseline, both groups had statistically significant improvement in rTNSS (p < 0.05). No serious AEs were reported in either group during the study period. Overall, 19 AEs were reported in the OLO + FNS group and 29 AEs were reported in the AZE + FNS group. OLO, when administered adjunctively with FNS, is effective, safe, and well tolerated in patients with SAR. PMID- 20302684 TI - Alberta Aboriginal Head Start in Urban and Northern Communities: longitudinal study pilot phase. AB - Aboriginal Head Start in Urban and Northern Communities (AHSUNC) is a federally funded, national, early childhood intervention strategy that addresses the needs of Aboriginal preschool children and their families. A pilot study, based on principles of community-based research, evaluated an Alberta Aboriginal Head Start (AHS) program offered off-reserve in Alberta. Overall, the results pertaining to children having followed an AHS program are positive. This phase 1 of a broader longitudinal evaluation study of all AHS sites in Alberta has led to the creation of several recommendations, which reinforce this type of evaluation and look to mitigate the limitations encountered in phase 1 (around available data, tools and context). PMID- 20302685 TI - The comorbidity burden of the treated asthma patient population in British Columbia. AB - To date there has been little investigation of the prevalence of comorbid conditions in asthma patients. Using 1996/97 cross-sectional health services administrative data for British Columbia, we compared the prevalence of comorbid conditions in treated adult asthma patients with the general adult population using a standardized comorbidity identification methodology, the Adjusted Clinical Group (ACG) Case-Mix System. We also profiled the comorbidity burden of pediatric asthma patients. Adults with asthma were significantly more likely to have a range of comorbidities, including respiratory infections, allergic rhinitis and 8 high impact/high prevalence chronic conditions (HIHPCCs). One in 4 adults with asthma had depression, the most prevalent HIHPCC. Children with asthma had a lower comorbidity burden than adults, but 12.6% had a stable or unstable chronic medical condition, with the most prevalent HIHPCC also depression. Adults with asthma had a high and complex comorbidity burden, particularly in terms of multiple chronic conditions. We discuss the implications for services planning and delivery. PMID- 20302686 TI - Gender, social relationships and depressive disorders in adults aged 65 and over in Quebec. AB - The objective of this study was to examine if social relationships have a differential association with the presence of depression in men and women aged 65 and over. Data came from a survey of a representative sample of 2670 community dwelling older adults in Quebec. Depressive disorders were measured using DSM-IV criteria. The prevalence of depression was 17.8% for women and 7.6% for men. Men reported a greater diversity of ties but less support than women. Having a confidant and/or being engaged in a good marital relationship was negatively associated with depression in both men and women. Compared with married people in general, widowhood was associated with a considerably higher risk of depression in men than in women. Compared with non-volunteers in general, men who volunteer were at considerably lower risk of depression than women who volunteer. This exploratory study could serve as a basis for future longitudinal studies on the impact of community activities and volunteering on the incidence and remission of depression in older men and women in Canada. PMID- 20302687 TI - [Hypertension Control in Communities (HCC): evaluation result of blood pressure management among hypertensive]. AB - OBJECTIVE: To determine the effects related to community-based standardized blood pressure management programs on the control of hypertension. METHODS: A protocol of community-based standardized blood pressure management was developed based on the current Chinese guideline for prevention, treatment of hypertension. Grass roots caretakers from community health service centers across China were trained using this protocol and required to manage hypertensive patients according to the protocol. Patients were treated on therapeutic life style change or/and medication, and followed up based on the criteria of risk stratification. The control rate of hypertension was evaluated after 1 year. Effect of intervention (EI) was estimated as '1 year rate (mean)' minus the number showed at the baseline. RESULTS: By the end of 2008, a total of 29 411 hypertensive patients (47.2% for male, mean age 61.4 +/- 10.9 years) with full information had been under management for one year according to the protocol. Among all patients, 8.9% were classified as under low risk, 50.8% as moderate risk and 40.3% as high and very high risk showed in baseline data. After standardized management, the EI of smoking, drinking and systolic/diastolic blood pressure were -7.1% (P < 0.05), 7.3% (P < 0.05), and -14.8-8.3 mm Hg (P < 0.05), respectively. However, EI of overweight/obesity was 0.3% (P > 0.05). For all patients, the control rate rose to 74.7%, with EI as 53.1%, and all of the sub-groups, including age, risk stratification, had significant increases. The longer the management was under, the higher the control rate was seen. Results from the multivariate logistic regression showed that older age, male and having higher blood level were adverse factors for the undertaking the control and management programs of hypertension. CONCLUSION: Results from our study showed that standardized management could significantly improve the program on the control of hypertension at the community level, in China. PMID- 20302688 TI - [A prospective study on the association between lipid accumulation product or body mass index and diabetes]. AB - OBJECTIVE: To measure the association between lipid accumulation product (LAP) or body mass index (BMI) and diabetes. METHODS: In this prospective study, subjects were recruited and followed up for more than five years from the program "Prevention of Multiple Metabolic Disorders and MS in Jiangsu Province" (PMMJS). A total number of 3598 people participating in the follow-up program, with complete information. Incidence rates of diabetes and relative risk in different levels of LAP and BMI were compared and analyzed. Areas under the receiver operation characteristic curve for obesity indicators such as LAP, BMI, waist circumference (WC), waist-to-hip ratio (WHR) in predicting diabetes of cohort population were calculated. RESULTS: The number and the cumulative incidence of diabetes increased with the LAP levels in both men and women. After adjusting for age and other traditional risk factors on diabetes, the adjusted risk ratios (aRR) value of diabetes were 4.33 (1.34 - 14.01) for men and 5.04 (2.06 - 12.34) for women, between the highest and the lowest level of LAP groups. When further adjusted for BMI, the aRR value decreased to 3.15 (1.13 - 8.80) for men and 4.84 (2.16 - 10.84) for women. The number and the cumulative incidence of diabetes also increased with the BMI levels in both men and women but not significantly as the LAP showed, and the aRR values were 1.34 (0.61 - 2.93) for men and 1.69 (0.91 - 3.06) for women in the highest level of BMI group, when compared with the lowest level group. Again, when further adjusted for LAP, the aRR values decreased to 1.23 (0.59 - 2.69) for men and 1.39 (0.74 - 2.60) for women. The area under the ROC curve (AUC) for the four kinds of obesity indicators in predicting diabetes in the descending order were LAP, WHR, WC, BMI in both men and women. CONCLUSION: LAP seemed more associated to diabetes than to BMI. When comparing with weight gain, diabetes might be more closely associated with the lipid accumulation product. PMID- 20302689 TI - [Impact of psychosocial factors on suicide attempts in high school and college students, data from eight cities of China]. AB - OBJECTIVE: This paper aimed to report the rate of suicide attempts among adolescent and young students of eight cities in China, and to examine the impact of related psychosocial factors on suicide attempts. METHODS: The investigation was obtained in senior and junior high school and college students in eight cities of China. All of the 17 622 participants were recruited to complete anonymous questionnaires regarding their experiences of suicide attempts and related psychosocial factors. RESULTS: Overall, 2.2 percent of the respondents reported that they had experienced attempted suicide during the previous year. Scores on high anxiety (OR = 2.61, 95%CI: 1.64 - 4.16), high depression (OR = 2.05, 95%CI: 1.35 - 3.10), suicide idea (OR = 14.21, 95%CI: 9.88 - 20.43), suicide plan (OR = 3.50, 95%CI: 2.59 - 4.73) were revealed as common risk factors while the whole time span being accompanied by mothers during juvenile years (OR = 0.38, 95%CI: 0.20 - 0.74) seemed to be protective factor for suicide attempts through multivariate logistic regression analysis. CONCLUSION: Our results showed that emotional symptom, idea and plans for suicide were statistically associated with suicide attempted in high school and college students. PMID- 20302690 TI - [Status of 'internet addiction disorder' (IAD) and its risk factors among first grade junior students in Wuhan]. AB - OBJECTIVE: To understand the epidemiological characteristics and influential factors on internet addiction disorder (IAD) among first-grade junior students in Wuhan city. METHODS: An anonymous questionnaire survey was carried out on 1219 first-grade junior students through stratified cluster sampling in 4 middle schools in Wuhan city. RESULTS: The internet use rate (IUR) of first-grade junior students was 96.43%, with the average of primary surfer age as 8.93 +/- 1.95. The internet addiction tendency (IAT) rate and the IAD rate were 10.87% and 7.71% respectively. The IAT and the IAD detection rates among male students were significantly higher than in female students (chi(2) = 13.04, P < 0.01). By ordinal logistic regression analysis, the relative factors mainly involved 6 aspects in IAD, including sex, poor academic performance, the surfer number of times, the surfer time, the surfer place and the surfer expense. CONCLUSION: The prevalence rates of IAT and IAD were quite high in the first-grade junior students in Wuhan. School authorities, teachers and guardians should collaboratively working together to guide the students in using the network correctly, and to carry out effective interventions to reduce the incidence of internet addiction. PMID- 20302691 TI - [Study on the relationship between childhood non-intentional injury and socio economic status in Jiangxi province]. AB - OBJECTIVE: To understand the relationship between childhood non-intentional injury and socio-economic status (SES) in Jiangxi province. METHODS: Nearly 100 000 households were selected by PPS sampling method, in Jiangxi province. All children aged 0 - 17 years in selected households were surveyed using an 'injury questionnaire'. SES was calculated under the World Bank method. RESULTS: 98 335 children were surveyed and the identified number of non-intentional injury cases was 5429 and with 52 fatal cases. The morbidity was 5.52% and mortality was 52.88/100 000. The mortality of children with higher SES was lower than that of other groups but without statistical significance. The morbidity of moderate injury increased with the increasing SES, also without statistical significance. However, the morbidity of severe injury in male children decreased with the increasing SES. Rates of moderate injury morbidities of fall and road traffic injury also increased with the increasing SES. Moderate injury morbidity caused by animals decreased with the increasing SES. Severe injury morbidity of fall decreased with the increasing SES. CONCLUSION: The morbidity of injury in children was affected by the SES and the relationship between injury and SES varied along with the results of different types of injuries. PMID- 20302692 TI - [Evaluation on the health education program regarding prevention of non-fatal drowning among school-aged children in Lianping county, Guangdong province]. AB - OBJECTIVE: To evaluate the outcome of health education program on drowning prevention among primary and secondary school children in rural areas. METHODS: A township was selected and all the students from grade 3 to 5, grade 7 to 8, and grade 10 to 11 were selected to take part in the program. Twelve intervention measures on natural water safety and drowning prevention were carried out for one year. Information was collected using the same questionnaire before and after the intervention program. RESULTS: One year after the intervention was carried out, children's knowledge on drowning prevention improved significantly (13.21, 95%CI: 12.51 - 13.90), and a positive effect was also noticed among boys (12.77, 95%CI: 11.77 - 13.77), girls (13.80, 95%CI: 12.82 - 14.78), and among primary school children(15.51, 95%CI: 14.30 - 16.72), senior high school children (10.78, 95%CI: 9.50 - 12.05) and junior high school children (12.77, 95%CI: 11.84 - 13.71). Overall rates on risk behaviors dropped from 41.4% to 32.2% (by 22.2%) including 15.6% for boys, 35.2% for girls and 13.8%, 29.3%, 26.3% for primary school children, senior high school children, junior high school children, respectively. The incidence rates for non-fatal drowning decreased by 58.9% (from 5.6% to 2.3%). The person-times for treatment on sight, in emergency settings, in outpatient clinic or in the hospitals had a reduction from 399, 78, 36 to 175, 32, 14, respectively. CONCLUSION: Health education program could improve children's perception on water safety, and reduce their risk behaviors as well as on the incidence of non-fatal drowning in the rural areas. PMID- 20302693 TI - [A matched case-control study on risk factors related to sports injuries in primary and secondary school students in Guangzhou]. AB - OBJECTIVE: To investigate the risk factors and to provide evidence for prevention and reduction of sports injuries in primary and secondary school students in Guangzhou. METHODS: 1:1 case-control study was conducted on both 349 cases and controls under the same distribution of sex, age and grade. Conditional univariate and multivariate logistic regression were used to explore the relationships between risk factors and injuries. RESULTS: Severe soles wear (OR = 7.20, 95%CI: 2.37 - 21.84), tiredness (OR = 14.34, 95%CI: 2.29 - 89.66) or sickness (OR = 1.96, 95%CI: 1.29 - 3.06) when participating in sports at a high frequency and history of previous injuries (OR = 2.11, 95%CI: 1.41 - 3.96) were risk factors related to sports injury while guidance by teachers and physical education provided by teachers during training (OR = 0.46, 95%CI: 0.26 - 0.79), appropriate protection (OR = 0.36, 95%CI: 0.20 - 0.64) as well as warming-up exercise (OR = 0.31, 95%CI: 0.14 - 0.67) at a high frequency were protective factors for sports injury. CONCLUSION: Prevention and control on sports injury need to improve the awareness on sports safety for students and teachers in order to develop positive behavior on sports safety. PMID- 20302695 TI - [Body vitamin D content and its relationship with body composition of children in Huairou district of Beijing]. AB - OBJECTIVE: To analyze vitamin D concentration and its association with body composition of children in Huairou district of Beijing, to provide evidence for evaluation and improvement of nutritional status of vitamin D in children. METHODS: Totally, 381 children aged 7 - 11 years were recruited in Huairou district of Beijing (40.3 degrees N). Samples of overnight fasting venous blood (drawn between 0630 and 0900) were obtained in late March. Serum 25 hydroxyvitamin D [25(OH)D]concentration was determined by ELISA kits (IDS Ltd, UK). Body composition indices of the whole body, the distal and proximal forearm were measured using dual-energy X-ray absorptiometry (DEXA, Norland, USA). RESULTS: The average serum 25(OH)D concentration of all subjects was (44.4 +/- 12.5) nmol/L. The percentage of vitamin D insufficient [serum 25(OH)D < / = 50 nmol/L] reached as high as 68.5% (261 people). The 25(OH)D concentration of boys (46.3 nmol/L +/- 13.3 nmol/L)was significantly higher than that of girls (42.0 nmol/L +/- 11.1 nmol/L), (t = 3.38, P < 0.01). Between the serum 25(OH)D concentration and lean body mass of proximal forearm, distal forearm, whole body, and four limbs, significant positive correlations (r = 0.13 - 0.19, P < 0.05)were observed. After age, gender, height and weight were under controlled for, correlations between the serum 25(OH)D concentration and lean body mass at proximal forearm, and the two lower limbs still existed (r = 0.12-0.14, P < 0.05). The serum 25(OH)D concentration, the percentage of body fat at proximal forearm, and distal forearm were negatively correlated (r = -0.14, P < 0.05; r = 0.11, P < 0.05). However, after adjusting for confounding effects, this correlation disappeared. No significant correlation between the serum 25(OH)D concentration and body fat was observed at any position. CONCLUSION: Vitamin D deficiency was common in children of suburb area of Beijing. Vitamin D status was positively associated with the lean body mass. PMID- 20302694 TI - [A prospective study on the current status of repeated injuries and its risk factors in middle school and college students]. AB - OBJECTIVE: To examine the epidemiological features and relative risk factors of repeated injuries among middle, high and college students in Ma'anshan city of Anhui province. METHODS: A prospective study on repeated injuries for 1-year follow-up period was carried out among 1494 students from 3 middle schools or colleges. Risk factors for repeated injuries were analyzed with multivariate logistic regression model. RESULTS: 799 students suffered 1639 episodes of injuries, with an incidence rate of 53.48%. The repeated group consisted of 200 students who suffered 854 injuries, accounted for 52.10% among the total injuries. RESULTS: from Multi-normal logistic regression analysis showed that male, number of family members of 4 or over, extraversion of character trait, and upper quartile of self-rating anxiety symptoms were the risk factors for the occurrence of repeated injuries. Moderate or well-of family income, mothers with senior high school education, and upper quartile of self-rating depression symptoms were protective factors for repeated injuries. CONCLUSION: Socio demographic factors and emotional status may predict the occurrence of repeated injuries that called for further study. PMID- 20302696 TI - [Tracing the sources of newly reported HIV infections in Dehong prefecture of Yunnan province]. AB - OBJECTIVE: To trace and provide HIV-testing among those having contacts with HIV infected individuals at various levels in Dehong prefecture, Yunnan province and to evaluate the effectiveness and feasibility of such investigation as a supplemental strategy for HIV testing and control. METHODS: Newly reported HIV infections from August throughout October in Dehong prefecture, in 2008 were asked to provide contact information of persons whom they had high risk contacts with. Persons having had risk contacts with HIV-infected cases were here of interviewed and their blood tested on the sero-status of HIV. RESULTS: A total of 335 HIV cases were newly reported during this three-month period. A total of 309 cases of them and 148 HIV infections identified thereafter from their risk contacts were under informed consent, to participate in this study. A total number of 3395 risk contacts were reported, of whom only 20.7% (704/3395) had 'contact information' and 51.3% (361/704) were successfully located and interviewed, including 117 previously confirmed HIV infections and 244 people with unknown HIV status. The majority of them (203 or 83.2% of 244) were then tested for HIV and 56 (27.6% of 203) were tested positive for HIV. The proportion of having detailed contact information and the proportion of being traced or followed among reported risk contacts of HIV infections were 68.8% and 68.2% for spouses of HIV patients, respectively, which were much higher than those among commercial sex partners (1.2% and 16.7%), casual sex partners (37.3% and 22.3%) and peers who sharing needles (34.1% and 56.4%). CONCLUSION: Newly reported HIV infections reported a large number of risk contacts and new HIV infections were identified among them. It was extremely difficult to trace commercial sex partners or casual sex partners on their HIV infection status. Nevertheless, tracing the risk contacts of newly reported HIV infections seemed to be helpful in identifying new HIV infections and in understanding the nature of transmission towards controlling the HIV epidemics. PMID- 20302697 TI - [An epidemiological study on the norovirus detected in the field environment after an outbreak of norovirus gastroenteritis]. AB - OBJECTIVE: To study the status of norovirus in environment of the patient's residence and water samples after a norovirus gastroenteritis outbreak, to provide evidences for the development of strategies for prevention and control of the disease. METHODS: After a norovirus gastroenteritis outbreak, anus swabs from the patient, swabs from the household environment and the water samples were collected to detect the norovirus by RT-PCR methods. Sequencing analysis was conducted on those positive specimens. RESULTS: Three specimens of the anus swabs from 9 patients and 2 samples of the 46 house environment swabs were positive to the virus. The latter were from the surface of water-closets of two families that the illness were asymptomatic. Among 5 water samples, only one was positive, which was the rivulet water that the feces of the villagers evacuated directly. RESULTS: showed that the sequences of the virus detected from the anus swabs of the patients, the swabs from the household environment and the samples of the rivulet water belonged to the same species. CONCLUSION: It is necessary to strengthen activities as supervision and disinfection to the feces of the patients, especially on monitoring the feces that might have contaminated the water during the norovirus gastroenteritis outbreak. PMID- 20302699 TI - [Etiologic and molecular characteristics of Vibrio parahaemolyticus strains isolated from diarrheal patients in Shenzhen, in 2007 - 2008]. AB - OBJECTIVE: To study the infection status and the molecular characteristics of Vibrio parahaemolyticus isolated from diarrheal patients in Shenzhen, in 2007 to 2008 and to provide evidence for the prevention and control of diarrheal diseases caused by Vibrio parahaemolyticus. METHODS: More than 80 fecal specimens from four sentinel surveillance hospitals were collected and cultured each month. A total of 361 isolates of Vibrio parahaemolyticus were sero-typed and examined by real-time PCR for the presence of two major virulence genes, tdh and trh. Of 361 strains, 60 O3: K6 strains isolated from six suspected outbreaks in August, 2007 and in September, 2008 were typed by pulsed-field gel electrophoresis (PFGE). RESULTS: 4384 stool samples were detected in four sentinel surveillance hospitals and with 361 Vibrio parahaemolyticus strains isolated that belonged to 28 serotypes. Serotype O3:K6, O4:K8 and O1:KUT accounted for 67.90%, 7.50% and 6.10%, respectively. Of 361 strains, 337 strains belonged to tdh+trh-, 11 strains were tdh-trh- and 13 strains were tdh+trh+. The most prevalent serotype which caused diarrheal diseases was tdh+trh in Shenzhen. The 60 isolates were discriminated into twenty different PFGE patterns, which belonged to three clones. Among the 60 isolates, most of the PFGE patterns of isolates from the suspected outbreak locations were identical and some strains isolated from different year were different. CONCLUSION: Vibrio parahaemolyticus isolates in Shenzhen were dominated by O3:K6 strains. Most of these isolates carried tdh gene and few carried trh gene. Meanwhile, the identical patterns of isolates from 6 suspected outbreaks locations demonstrated that Vibrio parahaemolyticus outbreaks occurred in July 2007 and in September 2008 in Shenzhen. However, the dominated strains' PFGE patterns were different each year, indicating that the sources of Vibrio parahaemolyticus had a multiplex nature and the multiplex sources such as water, sea food and pickled products should be integrated monitored. Laboratory based surveillance of diarrheal diseases could contribute in establishing early warning system for the better prevention and control of diarrheal diseases. PMID- 20302698 TI - [Hepatitis E virus (HEV) genotype and the prevalence of anti-HEV in 8 species of animals in the suburbs of Beijing]. AB - OBJECTIVE: To investigate the prevalence of anti-hepatitis E virus (HEV) and genotypes of hepatitis E virus in 8 species of animals including swine, cattle, sheep, horse, donkey, dog, chicken and duck in the suburb of Beijing. METHODS: Serum samples were collected from the 8 species of animals, and fecal samples of younger swine were collected from 2 stock farms. Anti-HEV was detected by Double Antigen Sandwich Assay. HEV RNA from fecal samples was detected by a reverse transcription nested polymerase chain reaction (RT-nPCR). Parts of the PCR products were cloned and sequenced. The swine HEV sequences were analyzed genetically. RESULTS: The positive rates of anti-HEV in serum specimens of swine, cattle, horse, donkey, sheep, dog, duck and chicken were 80.43% (481/598), 15.02% (52/346), 14.29% (40/280), 0 (0/26), 9.88% (33/334), 0 (0/21), 3.03% (7/231) and 2.53% (8/316), respectively. The anti-HEV prevalence of adult swine (>/= 6 months) and younger swine ( < / = 3 months) were 87.86% (369/420) and 62.92% (112/178) respectively. 74 of 111 (66.67%) pig faces were positive for HEV RNA. Sequence analysis on these positive samples showed that there were 6 groups of HEV designated as bjsw1, bjsw2, bjsw3, bjsw4, bjsw5 and bjsw6. The 6 strains of HEV shared 94.5% - 99.6% sequence identity of partial HEV ORF2 nucleotide with each other. The identities of HEV ORF2 nucleotide sequences between the 6 strains and genotype 1, 2, 3 and 4 were 75.6% - 78.6%, 75.6% - 76.2%, 77.1% - 80.7% and 83.7% - 94.5%, respectively. The sequence identity between the 6 strains and human HEV genotype 4d was 90.0% - 94.5%. CONCLUSION: HEV infection was seen in swine, cattle, horse, sheep, duck and chicken in the suburbs of Beijing. The anti HEV positive rate appeared the highest in swine and the lowest in dog and donkey. The six strains of HEV isolated from younger swine belonged to genotype 4d. PMID- 20302700 TI - [Study on the characteristics of major mosquito-borne infectious diseases in Three Gorges Reservoir Area from 1997 to 2008]. AB - OBJECTIVE: Characteristics and tendency of mosquito and major mosquito-borne diseases (including epidemic encephalitis B and malaria) were analyzed in the Three Gorges Reservoir Area from 1997 to 2008. METHODS: Information on surveillance data related to mosquito-borne infectious diseases and on mosquito density and category, from 1997 to 2008 was collected from Health Surveillance System in Three Gorges Reservoir Area. Data regarding meteorological factors and construction of Three Gorges Reservoir was also collected. Pearson and Poisson models were used. RESULTS: From 1997 to 2008, in the Three Gorges Reservoir Area, the incidence rates of epidemic encephalitis B and malaria were decreasing. Positive correlations were shown between indoor and outdoor mosquito density as well with temperature with coefficient as 0.281 and 0.355 respectively. Correlations of mosquito-borne diseases with indoor and outdoor mosquito density were positive, with correlation coefficient as 0.340 and 0.328 respectively. CONCLUSION: There seemed lack of evidence to prove that negative influences had occurred on the incidence of mosquito-borne infectious diseases or the mosquito density after the Three Gorges Reservoir water storage came into being in 2003, however, long-time surveillance program needs to be carried out to gather information on this issue. PMID- 20302701 TI - [Comparative analysis of three diarrhea-household-surveys in Guangxi]. AB - OBJECTIVE: To study the epidemiological characteristics and the effects of control measurements in Guangxi by comparing the results from diarrhea-household surveys conducted in the three different periods of time and to develop control strategies. METHODS: Data on the incidence, health care seeking and treatment of diarrhea from three household surveys conducted in 1988, 1995 and 2007 was analyzed using SPSS (version 13.0). RESULTS: The incidence rates of diarrhea over the three periods of time were 0.562, 0.456 and 0.221 per person-year, respectively (P < 0.001). No significant difference was found in the incidence between males and females. The disease mainly attacked young age groups and those with lower educational levels. In recent years, longer durations of disease but less severe were observed in patients with diarrhea. The patients mainly visited first line health services with a health care seeking rate of 28.3%. Antibiotics were used by most of the patients (49.8% - 90.2%), while the rate of using oral rehydration salts (ORS) was only 1.4% - 11.5% but the use of traditional Chinese medicines has increased. Intake of untreated water, contaminated foods and contact with patients were important risk factors on diarrhea. CONCLUSION: The prevalence of diarrhea in Guangxi had declined and the health seeking rate was low in the past two decades. It is necessary to further regulate the treatment, in order to strengthen the health education programs to the general population, in order to improve the accessibility of health services and to increase both the health care seeking rate and effective diagnosis rate. PMID- 20302702 TI - [Identification and phylogenic analysis of Coxsackie-virus B5 during an outbreak of aseptic meningitis in Shandong]. AB - OBJECTIVE: To identify the pathogen that caused an outbreak of aseptic meningitis in Shandong province in 2005. Phylogenic analysis was carried out on Coxsackie virus B5 (CVB5) which was isolated during this outbreak. METHODS: 78 stool and 58 cerebrospinal fluids (CSF) specimens were collected from some inpatients during this outbreak. Virus isolation and reverse transcription-polymerase chain reaction (RT-PCR) was then performed. Phylo-genetic trees based on entire and partial VP1 sequences were constructed among CVB5 isolates and others published in GenBank. RESULTS: The isolation rates of stool and CSF specimens were 38.5% (30/78) and 48.3% (28/58) respectively. Among the results of serotype identification and molecular typing of 58 positive isolates, 54 were identified as CVB5, 2 as ECHO24, 1 as CVB3 and 1 as CVA9. Results from viral investigation showed that CVB5 was the main pathogen causing this outbreak. Data from homological comparisons indicated that Shandong strains had the highest nucleotide acid identity with the Zhejiang/12/02 strain (97.5% - 97.8%), and lower identity (78.3% - 78.6%) with the prototype strain (Faulkner strain). Phylogenic tree in VP1 region showed that CVB5 could be separated into four genotypes. Isolates of this outbreak belonged to genotype D. CONCLUSION: CVB5 was the major etiological agent correlated with this outbreak. The shift of predominant genotype might serve as one of the causes that associated with the outbreaks of aseptic meningitis. PMID- 20302703 TI - [Clone expression of the caf1 gene of Yersinia pestis and immunological evaluation on recombinant F1 antigen]. AB - OBJECTIVE: To get recombinant F1 antigen (rF1) and to construct the detection dipstick of plague antibody. METHODS: The caf1 gene removing the signal peptide coding sequence was cloned into plasmid pET32a(+) by double-digested sites of BamHI and Not I. Recombinant plasmid caf1-pET32a(+) was transformed into BL21 (DE3) and the rF1 was expressed. Expression products were purified by affinity chromatography. Dual detection dipstick of plague antibody was constructed with purified rF1 and natural F1, and evaluated with 528 human serum samples of Zhejiang province. RESULTS: The fusion protein rF1 of 35.5 KD was expressed by BL21 strains containing caf1-pET32a(+). The sensitivity of rF1 showed equivalent to or higher than the natural F1 antigen in detecting plague antibody. It seemed that there was a better consistency of 97.9% (kappa = 0.466) when 528 human sera was detected by rF1 and natural F1. CONCLUSION: We successfully extracted the rF1 with good immunological activity that might be used to detecting Yersinia pestis. PMID- 20302704 TI - [Sequencing and analyses on glycoprotein gene of rabies viruses isolated in Zhejiang province, China]. AB - OBJECTIVE: Based on sequencing the genomes of glycoprotein (GP) gene of rabies viruses isolated in Zhejiang, we analyzed the properties of rabies viruses genetic variation in molecular level, and to compare with those of other representative vaccine strains and street virus strains, get the information about rabies viruses variation. METHODS: Suckling mice against rabies virus were selected. Overlapped fragments were amplified by RT-PCR and full-length genomes were assembled to analyze the nucleotide and deduced protein similarities and phylogenetic analyses of the GP genes. RESULTS: The fourteen full-length genomes were completely sequenced and they had the same genetic structure with 1575 nts and deduced protein with 524 aa. Genetic analysis revealed that the nucleotide and amino acid homologies of GP gene from Zhejiang strains and other vaccine strains or street virus strains were 82.3% - 99.9% and 85.1% - 99.8%. The fourteen strains were genotype 1 according to the phylogenetic analyses. The GP amino acids of Zhejiang strains rabies virus strains without any recombination occurred in GP and no larger variation appeared in the major antigenic sites. CONCLUSION: The comprehensive analysis based on the first-level structure of GP demonstrated that it was possible that some advantageous antigenic epitopes existed in certain areas and potential antigenic determinants. It was evident that the GP gene of Zhejiang strains appear to be stable and their sequence similarity with the representative strains of street virus in China were higher than those of other vaccine strains. Some differences showed in the genetic structure and evolution relationship among Zhejiang strains, other street strains in other regions and vaccine strains. PMID- 20302705 TI - [Detection of circulating antigen of Angiostrongylus cantonensis by 12D5 and 21B7 monoclonal antibodies]. AB - OBJECTIVE: To detect the rate of Angiostrongylus cantonensis infection and to study the effects of treatment so as to prepare monoclonal antibodies (McAbs), and gold immunochromatography assay (GICA) with 12D5 and 21B7 McAbs could be prepared in advance. METHODS: Two McAbs (12D5 and 21B7) were applied to detect the circulating antigen (CAg) in the sera of rats infected with A. cantonensis and angiostrongyliasis patients respectively by double antibody sandwich ELISA. Either 12D5 or 21B7 McAbs was used as antibody and protein A was conjugated with colloid gold as the detection marker. A special pad for GICA was designed according to the reaction procedure, and CAg were detected by GICA in the sera of rats infected with A. cantonensis and angiostrongyliasis patients respectively. RESULTS: 12D5 McAb was identified as IgG1 and 21B7 McAb was IgM. Results from Western blotting showed that two McAbs could be used to identified 55 KD protein of adult worms of A. cantonensis. The detection rates of CAg in the sera of infected rats was 100% (48/48) and the detection rates of CAg in the sera of angiostrongyliasis patients was 100% (32/32). No cross-reaction to sera of patients with other infection of parasites, such as clonorchiasis, fasciolopsiasis, ancylostomiasis, ancylostomiasis, anisakiasis as well as schistosomiasis wee seen and normal sera did not react with 12D5 and 21B7 McAbs. CONCLUSION: Results from sandwich ELISA and GICA with 12D5 and 21B7 McAbs showed high specificity and acting as detecting CAg of A. cantonensis in sera of infected animals and patients. We noticed that GICA with 12D5 and 21B7 was not only rapid and simple that without requirement of special instrument, but also rather sensitive and specific for the detection of current infection with A. cantonensis. PMID- 20302706 TI - [Association between methylthioadenosine phosphorylase gene single nucleotide polymorphisms and myocardial infarction in Chinese Han ethnicity]. AB - OBJECTIVE: To investigate the association between methylthioadenosine phosphorylase (MTAP) gene single nucleotide polymorphisms (SNP) and myocardial infarction (MI) in the Chinese Han ethnicity. METHODS: 432 patients suffered from myocardial infarction and 430 controls were involved for case and control groups, respectively. Nine tag SNPs in MTAP gene were selected and genotyped. RESULTS: We found no significant association of selected tag SNPs with MI in all of the samples. However, in stratified analysis, significant association was observed at rs7027989 in male subjects. The risk of MI increased by 26% (P = 0.005) for male subjects of minor allele carriers in a dominant model. The increased risk of MI at rs7027989 remained significant after adjusting for confounding factors. CONCLUSION: MTAP gene might be involved in the etiology of MI in Chinese Han ethnicity. PMID- 20302707 TI - [Covariance analysis on the change of quality of life affected by percutaneous coronary intervention for patients with coronary heart disease]. AB - OBJECTIVE: To compare changes of quality of life at 3 months from baseline among patients who underwent and did not undergo percutaneous coronary intervention (PCI). METHODS: Sixty one patients with coronary artery disease, who were hospitalized in Cardiology Department in March 2008, were followed-up for 3 months after being discharged. SF-36 and QOL-35 were administered before PCI and at 3 months. Patients were divided into 2 groups according to whether they underwent PCI. Changes of quality of life scores between PCI and non-PCI groups were compared using analysis of covariance. RESULTS: There were 24 cases in non PCI group and 37 in PCI group. Baseline characteristics were well balanced between PCI and non-PCI groups except gender (67.6% vs. 28.6% for male, P = 0.005), history of angina (56.8% vs. 23.8%, P = 0.015), smoking history (51.4% vs.23.8%, P = 0.037) and Judkins classification of coronary artery (P = 0.001). Multivariate analysis of covariance showed that the change of life quality between non-PCI group and PCI group in 3-months after discharge had statistical differences in total scores (P = 0.044) and mental health scores (P = 0.003) of SF-36, total scores (P = 0.039) and social function scores (P = 0.007) of QOL-35. CONCLUSION: PCI can improve life quality in patients with coronary artery disease. PMID- 20302708 TI - [Retrospective seroepidemiology study of Toxoplasma gondii infection in the population of recruits]. PMID- 20302709 TI - [Application of 'stepped-wedge design' methodology in randomized controlled trials]. AB - In this article, two research cases are employed to show the rationale of the stepped-wedge design, under what situations that such a design is desirable, and how it can be implemented. Stepped-wedge design seems to suit to randomized controlled trials in which the entire study population will receive intervention programs as they would "provide more advantages than harm". When intervention can not be given to all the targets simultaneously due to limited resources, this design is particularly useful. The stepped-wedge design is also relevant when there is a hope to detect or control the time trend effect on the effectiveness of the intervention strategy. On the other hand, however, this design requires longer trial duration and presents a number of statistical challenges. Hence, careful planning and monitoring are essential to ensure that a robust evaluation is undertaken. PMID- 20302710 TI - [Application of flexible matching strategy to detect gene-environment interactions for increasing the study power]. AB - INTRODUCTION: Flexible matching has recently been proposed as a method of improving interactions efficiency. In this study, the concept of flexible matching has been introduced, and the applicability of this strategy has also been described based on the power calculation of interaction between HER-2 polymorphism and smoking with breast cancer. A large-sample approximation method is used to estimate the power and efficiency of gene-environment interactions. In the basic scenario, power of interaction between HER-2 polymorphism and smoking of unmatched case-control study appears to be 30% while in the frequency matching case-control study it is 56%. However, when increasing the smoking prevalence in controls, greater power can be obtained (power = 74%). CONCLUSIONS: Flexible matching strategies can increase the power and efficiency of case-control studies to detect and estimate the gene-environment interactions when compared with traditional frequency matching and it is especially useful under those scenarios when low environmental exposure of population, adverse gene-environment interactions or less paired controls are seen. Optimal matching design should be made available by weighing the benefits and loss due to flexible matching. PMID- 20302711 TI - [The epidemiological characteristics and risk factors of child pedestrian injury.]. PMID- 20302712 TI - [Molecular epidemiology of rotavirus in children with acute diarrhea in Shanghai port area]. PMID- 20302713 TI - [Analysis on the hemagglutinin genetic characteristics of 2009 novel influenza A (H1N1) virus in Changsha, Hunan province]. PMID- 20302714 TI - [Sequence analysis of 3 virulence factors from Streptococcus suis serotype 2 isolates in Zhejiang province]. PMID- 20302715 TI - [Analysis of human coronavirus NL63 in 690 children with acute respiratory infection in Shanton]. PMID- 20302716 TI - [Study on the prevalence and genotype of commensal Escherichia coli producing AmpC beta-lactamase isolated from health chicken]. PMID- 20302717 TI - [A strain of Klebsiella pneumoniae harboring four kinds of beta-lactamases]. PMID- 20302718 TI - [Comparison of AIDS related high risk behavior between college students and the same age non-college students in men who have sex with men]. PMID- 20302719 TI - [Association between hemoglobin levels before pregnancy and during pregnancy]. PMID- 20302720 TI - [Epidemiological study on injuries among primary and secondary school students in Guangzhou]. PMID- 20302722 TI - [The retrospective study of transjugular intrahepatic portosystemic shunt with covered or uncovered stents in patients with portal hypertension]. AB - OBJECTIVE: To retrospectively compare the clinical outcome in patients with portal hypertension treated with transjugular intrahepatic portosystemic shunt (TIPS) using Fluency stent-graft (PTFE-covered stents) or bare stents. METHODS: Approval of study and treatment protocol and waiver of informed consent for the retrospective study were obtained from institutional review board. Informed consent was obtained from each patient before procedure. Sixty consecutive patients with portal hypertension treated with TIPS from April 2007 to April 2009 were included. TIPS creation was performed with Fluency stent-graft in 30 patients (group A) and with bare stents in 30 patients (group B). Liver function, TIPS patency and clinical outcome were evaluated every 3 months. RESULTS: During hospitalization, there was no hepatic encephalopathy and recurrency of variceal bleeding.Acute shunt occlusion was observed in one patient with group A and another patient with group B.Follow-up was performed with average time of (6.2 +/ 3.9) months in group A and (8.3 +/- 4.4) months in group B. The rates of recurrent bleeding, acute shunt occlusion, hepatic encephalopathy and death were 3.3% and 20.0%, 0 and 30.0%, 16.7% and 20.0%, 0 and 13.3% in group A and B. The rates of recurrent bleeding, acute shunt occlusion and death in group A was lower than those in group B. There was no difference of hepatic encephalopathy between group A and B. The decrease of portal pressure and portosystemic pressure gradient, and the increase of portal flow and shunt flow in group A were higher than those in group B. There were no difference of liver function, ammonia and MELD between group A and B. CONCLUSIONS: Fluency stent-graft is safe and effective in TIPS creation, with high patency rate. Covered-stent can improve the clinical outcome of portal hypertension. PMID- 20302723 TI - [Impact of diabetes mellitus on clinicopathological factors and prognosis of patients with colorectal cancer.]. AB - OBJECTIVE: To analyze the impact of diabetes mellitus on the clinicopathological factors and prognosis of patients with colorectal cancer. METHODS: A total of 599 patients with colorectal cancer treated between January 2000 and June 2007 were collected retrospectively. The patients were divided into diabetes mellitus (DM) group and non-diabetes mellitus (NDM) group. The pathologic factors data was compared between the two groups, and the Logistic multivariable analysis was performed. The Cox regression model analysis of prognosis data was applied in 402 patients who underwent radical surgery without preoperative neoadjuvant therapy. RESULTS: A total of 58 cases (9.7%) developed diabetes mellitus. Significant differences was found in the body-weight, age, hypertension between the two groups (P < 0.05), while no significant differences in the pathologic factors, such as tumor differentiation, invasion depth, lymph node involvement, TNM stage and lymphovascular invasion was found between the two groups (P > 0.05). There was no significant correlation between diabetes mellitus and the pathologic factors on the Logistic analysis (P > 0.05). Among the patients underwent radical surgery directly, neither disease progression curve (P = 0.521) nor overall survival curve (P = 0.909) presented significant differences between the two groups. It's not shown that diabetes mellitus was significantly associated with the prognosis of patients with colorectal cancer by using Cox regression analysis (P = 0.991). CONCLUSIONS: Diabetes mellitus does not significantly influence the clinicopathological factors and the prognosis of colorectal cancer in patients receiving radical surgery, and it requires more investigation. PMID- 20302724 TI - [Efficacy of anticoagulation on patency post-permanent inferior vena caval filter placements]. AB - OBJECTIVE: To discuss the efficacy of anticoagulation on patency post-permanent inferior vena caval filter (IVCF) placements. METHODS: The patients with deep vein thrombosis (DVT) of the lower extremity who were accepted permanent IVCF placement from December 2001 to December 2007 were reviewed retrospectively. Data on vital status, filter thromboembolism, anticoagulation time, and so on were obtained through follow-up. One hundred and thirty eight patients (75 male and 63 female) with a mean age of 65 years were enrolled in the study. All the patients were divided into non-anticoagulation group, anticoagulation group A with taking warfarin less than 6 months, or anticoagulation group B with taking warfarin more than 6 months. chi(2) test, t test, Kaplan-Meier survival curve, Log-rank test were used for statistics analysis. RESULTS: Sixteen patients died, and 1 of them died of pulmonary embolism. Including the 1 patient mentioned before, there were 19 patients (13.8%) suffered from filter thromboembolism. Upon chi(2) test, there were no significant differences (P = 0.288) on the patency rates between non anticoagulation, anticoagulation group A and anticoagulation group B (87.8%, 75.0%, and 88.3% respectively). Upon Kaplan-Meier survival analysis, there were still no significant differences (P = 0.227) on the mean patency time and the cumulate rates of patency at the 1st or 3rd year between the 3 groups (87.1%, 80.0%, 94.8% and 87.1%, 74.3%, 85.4% respectively). CONCLUSION: Anticoagulation has no efficacy on patency post-permanent IVCF placements. PMID- 20302725 TI - [Clinical features and surgical treatment of thoracic Castleman's disease]. AB - OBJECTIVE: To explore the clinical features and surgical treatment of thoracic Castleman's disease. METHODS: The clinical symptoms, pathological, laboratory, CT findings and results of surgery in 32 patients with Castleman's disease from June 1996 to November 2008 were evaluated. Among the 32 patients, there were 14 male and 18 female, aged from 16 to 48 years old with a mean age of 34.2 years old. Thirteen cases had symptoms including short of breath, irritable cough, or chest pain, while 14 cases had no symptoms. Mediastinal or hilar tumors were found by CT examination. RESULTS: Tumor was surgically removed in all the 32 patients except one died with anesthetic accident. Castleman's disease was conformed by pathology. Five cases were diagnosed as with paraneoplastic pemphigus, 3 of them were attacked by bronchiolitis obliterans. All 5 cases were failed by the use of prednisone. The signs of PNP were dissolved after operation, but pulmonary lesions failed to improve. There was no recurrence in all cases. CONCLUSIONS: PNP and lung abnormalities are the rare and severe complications of thoracic Castleman's disease. Surgical resection of the tumor is the first choice for treatment. PMID- 20302726 TI - [Positron emission tomography with special tracers in pulmonary abnormalities]. AB - OBJECTIVE: To assess the value of positron emission tomography (PET) with (11)C choline (CH), (11)C-methionine (MET), (18)F-fluorothymidine (FLT), and (11)C acetate (AC) in diagnosis of pulmonary abnormalities and the features of pulmonary abnormalities in PET. METHODS: From June 2002 to June 2007, 100 patients with pulmonary nodules or masses confirmed by CT scans received PET with special tracers. Fifty-eight patients received CH-PET, 16 patients received MET PET, 22 patients received FLT-PET, 4 patients received AC-PET. PET data was analyzed by visual method and semiquantitative method with standard uptake value (SUV). Diagnoses were compared with pathology and follow-up survey. RESULTS: For identification of pulmonary neoplasms with CH-PET, the sensitivity, specificity and accuracy were 84.2% (32/38), 57.9% (11/19) and 75.4% (43/57). In cancer cases, SUV had no correlation with tumor size or age. For identification of pulmonary neoplasms with MET-PET, the sensitivity, specificity and accuracy were 6/7, 6/9 and 75.0% (12/16). In cancer cases, SUV had not correlation with tumor size or age. For identification of pulmonary neoplasms with FLT-PET, the sensitivity, specificity and accuracy were 85.7% (12/14), 2/8 and 63.6% (14/22). In cancer cases, SUV had not correlation with tumor size or age. In AC-PET, only 1 case of pulmonary metastasis of kidney clear cell carcinoma showed acetate avid. Two squamous cell carcinoma and 1 adenocarcinoma didn't appear abnormal in AC-PET. CONCLUSION: CH, MET, FLT, AC are valuable in diagnosing but also lead to false positive and false negative. PMID- 20302727 TI - [Risk factors of recurrence after transurethral resection of the prostate due to benign prostate hyperplasia]. AB - OBJECTIVES: To review the clinic data of benign prostate hyperplasia (BPH) cases, and to find the risk factors of recurrence in post transurethral resection of the prostate (TURP) patients. METHODS: From November 2002 to November 2007, 1471 cases were reviewed, including 41 patients of recurrence after TURP. Record the data include onset age, course of disease, age of surgery, LUTS, PSA, blood serum creatinine, size of the prostate in transabdomen ultrasonography, data of urodynamic examination, weight of resected tissue, persistence time of the resection, length of stay, score of inflammation of the pathologic sample, experience of the operator, routine blood examination, routine urine examination and so on. Statistical analysis was performed using univariate and multivariate unconditional Logistic regression analysis for evaluation of the data. RESULTS: In the univariate analysis, onset age (t = 2.292, P = 0.086), PVR (t = 2.181, P = 0.03), size of the prostate in transabdomen ultrasonography (t = -1.987, P = 0.047), experience of the operator (Z = 10.13, P = 0.0015) and the symptom that bladder does not feel completely empty right after urinating (chi(2) = 9.240, P = 0.002) had statistical significance. In the multivariate unconditional Logistic regression analysis, Odds ratio (OR) of the factors were investigated, the symptom that bladder does not feel completely empty right after urinating (OR = 0.557), the score for inflammation (OR = 0.905) and experience of the operator (OR = 0.393) had statistical significance. CONCLUSIONS: The risk factors for elevating the incidence of post-TURP recurrence are the lower score for inflammation, younger onset age, having the symptom that bladder does not feel completely empty right after urinating, bigger size of prostate in transabdomen ultrasonography, lower post void residual urine volume and poor experience of the operator. PMID- 20302728 TI - [The effect of preoperative factors on the function of the cervical spine after cervical artificial disc replacement: a minimal 3 years follow-up]. AB - OBJECTIVE: To evaluate the effect of preoperative factors on the function of the cervical spine after Bryan artificial disc replacement. METHODS: Fifty patients who underwent cervical disc replacement from December 2003 to January 2006 were investigated. The preoperative factors such as long course of disease, lose of motion or disc height at the operation level were evaluated for their effects on the motion of the operated disc and clinical results at the time of final follow up. There were 35 males and 15 females. Thirty-nine patients received one-level disc replacement, 11 patients received two-level disc replacement. The age of patients was from 25 to 73 years, average was 49 years. RESULTS: Until January 2009, 50 cases of all the 53 patient who got operation for more than 3 years were followed up. The follow up period was from 36.0 to 55.6 months, which showed a skewed distribution, with a median of 41.9 months. The patients, who got neural syndrome for more than 3 years, would have worse JOA recovery rate through the surgery compared with the patients who got neural syndrome less than 3 month. As for radiographic results, the preoperative range of movement (ROM) at the implanted disc spaces was 10.4 degrees +/- 5.0 degrees which had significant correlation with the most recent follow-up ROM which was 8.6 degrees +/- 4.8 degrees (r = 0.325, P < 0.05). The group which height ratio of the operative disc and the adjacent discs was less than 0.87 would have worse JOA recovery rate and range of motion at operated level at the most recent follow-up than the group more than 0.87 with statistical significance. CONCLUSIONS: For the patients with cervical spondylosis or cervical disc herniation who get nervous syndrome for more than 3 years, will have worse JOA recovery rate through the surgery, so the patient should get the operation in time to achieve better improvement. When the operated level is severe degenerated, the motion of the replaced disc and the clinical results is dissatisfied at the time of final follow-up, so it is the relative contraindications for the cervical disc replacement. PMID- 20302729 TI - [Exploratory development of titanium mesh with bone allograft in treatment of cervical spinal tuberculosis]. AB - OBJECTIVE: To evaluate the exploratory development of bone graft by titanium mesh with bone allograft in treatment of cervical spinal tuberculosis. METHODS: Thirty two cases of cervical spinal tuberculosis treated with anterior radical debridement, decompression and inter fixation from January 2002 to January 2007 were included (at least two years follow-up). 18 male and 14 female, age from 18 to 72, mean 41.3 years old. 0.5 - 15.0 months before visit, mean 6.9 months. There were 13 cases in initial treatment group and 19 cases in retreatment group. All cases were divided into two groups (group A and group B) by resource of bone graft. Group A, titanium mesh with bone allograft, 17 cases. Group B, autograft with ilium, 15 cases. Operation time, blood loss, curing conditions, cervical curvature (absolute rotation angle, ARA), function of spinal cord and the rate for bone graft fusions in two groups were compared. The mean follow-up was 3.5 years (range 2 - 5 years). RESULTS: The primary healing rate of incisions was 93.8% (30/32), and total healing rate was 96.9% (31/32). There were no significant differences in operation time or in blood loss between two groups (P > 0.05). Operation time and blood loss, 72 min/121 ml in group A and 90 min/198 ml in group B, there were significant differences between two groups (P < 0.05). In each group, there were significant differences in the function of spinal cord between preoperative and immediately post operative, between preoperative and follow-up, and between immediately post operative and follow-up (P < 0.05), and there were significant differences in ARA between preoperative and immediately post operative, and between preoperative and follow-up (P < 0.05), and there were no significant differences between immediately post operative and follow-up (P > 0.05). On preoperative, immediately post operative and follow-up, there were no significant differences in the function of spinal cord or in ARA between two groups (P > 0.05). CONCLUSION: For cervical spinal tuberculosis followed by effective individual chemotherapy, a good effect can be obtained by treated with radical debridement and bone allograft with titanium mesh. PMID- 20302730 TI - [Analysis of middle-term outcome of the imaging characteristics after the percutaneous laser disc decompression]. AB - OBJECTIVE: To study the imaging findings outcome of the percutaneous laser disc decompression (PLDD) and evaluate the middle-term safety and efficacy of PLDD. METHODS: The imaging data of 22 cases suffered cervical spondylosis or lumbar spondylosis and treated by PLDD more than 3 years were retrospectively reviewed. To observe the intervertebral space of the invasive disc and the intervertebral disc hernia before and after the operation on the lateral projection of X-ray and the axial view of the MRI. To make a statistical analysis of the data. RESULTS: There was no obvious change of disc height involving the anterior disc height, the intermediate disc height and the posterior disc height after the PLDD at the final follow-up (P > 0.05). At last time follow-up, the Sagittal Index (SI) are 0.10 - 0.54 and 0.06 - 0.39 before and after the PLDD in the treatment of cervical vertebra. The statistical difference were significant (P < 0.05). In lumbar vertebra, the SI is 0 - 0.71 and 0 - 0.48 disc before and after the PLDD. The statistical difference were very significant (P < 0.01). CONCLUSIONS: The PLDD will not destroy the intervertebral space of the cervical and lumbar vertebra obviously; moreover, it can effectively reduce the disk hernia. The PLDD is a safe and effective Mini-invasive surgery for cervical vertebra and lumbar vertebra diseases. PMID- 20302731 TI - [One-stage total en bloc spondylectomy by anterior and posterior approaches for lumbar vertebral tumors]. AB - OBJECTIVE: To investigate the surgical results of one stage total en bloc spondylectomy (TES) by anterior and posterior approaches for lumbar vertebral tumors and evaluate its benefit for these tumors. METHODS: A total of 21 patients with the lumbar vertebral tumor treated with on stage TES by posterior and anterior approaches from April 2003 to August 2007 were reviewed, which included 14 males and 7 females with an average age of 47.6 years. Thirteen patients were suffered with the primary lumbar vertebral tumors and 8 patients were diagnosed for the lumbar vertebral metastasis tumors. There were 8 of S3, 3 of I A and 2 of II according to Ennekinng stage system. And there were 1 of Grade B, 4 of Grade C, 8 of Grade D, and 6 of Grade E according to Frankel grade system. The spinal reconstruction was obtained by titanium mesh filled with autograft for benign and low-grade malignant tumors and methylmethacrylate-filled titanium mesh for malignant tumors. The spinal stability was enhanced by posterior internal fixation with rod-screw system. RESULTS: The operation time was 250 min and bleed loss was 2100 ml on average. The follow-up period lasted from 1.0 to 5.5 years. All cases had pain before operation, among which 14 cases obtained complete relief and 7 cases obtained partly relief after operation. In all cases with neurological deficit, they improved neurologically by more than one grade using the Frankel grading system. Up to now, 1 patient had be local recurrence after operation and 4 patients were dead on the following time. The others still are alive and no local recurrence. CONCLUSION: One-stage TES by anterior and posterior approaches for lumbar vertebral tumor is feasible, safe and effective to lumbar vertebral tumor resection and stability reconstruction, which has many advantages such as controlling local recurrence, spinal cord decompression thoroughly, relieving the pain, improving the life quality and prolonging the lifetime. PMID- 20302732 TI - [A preliminary study of melatonin signaling transduction pathway in BMSCs from adolescent idiopathic scoliosis patients]. AB - OBJECTIVE: To investigate the melatonin signaling transduction pathway in BMSCs from adolescent idiopathic scoliosis patients. METHODS: Twenty-four volunteers aged 12 - 18 years were divided into two groups: AIS group was 15 and control group was 9. The human bone marrow anticoagulated by heparin was obtained from anterior superior iliac spine, and the BMSCs were isolated by density gradient centrifuge from the mononuclear cells, and then were cultivated and serial subcultivated in vitro. P3 cultures were analyzed by the flow cytometry to determine the surface antigens. P3 BMSCs were used to detect the melatonin signaling transduction pathway. The cellular cAMP was elevated using forskolin, and then the BMSCs were treated with melatonin to inhibit the cellular cAMP levels. RESULTS: Mononuclear cells were cultivated and subcultivated to P3 culture in vitro, which were analyzed by the flow cytometry, and demonstrated that the expanded mononuclear cells expressed mesenchymal cell markers. The basal cAMP levels of the two groups were very low, after the stimulation of forskolin, cellular cAMP levels increased rapidly in all the patients, but after the stimulation of melatonin at physiological dose or even at pharmacological dose, there was no statistical difference of the inhibition of cAMP between AIS group and control (P > 0.05). CONCLUSION: Melatonin signaling transduction pathway may be normal in BMSCs from AIS patients. PMID- 20302733 TI - [An experimental study of gemcitabine inducing pancreatic cancer cell apoptosis potentiated by nuclear factor-kappa B P65 siRNA]. AB - OBJECTIVE: To investigate the effect and mechanism of NF-kappaB P65 gene silencing by small interference RNA on the apoptosis of human pancreatic cancer cells induced by gemcitabine in vitro and in vivo. METHODS: Human pancreatic cancer cells (BxPC-3 and PANC-1) were cultured and respectively divided into five groups: blank control group, negative control siRNA group, gemcitabine group, NF kappaB P65 siRNA group and gemcitabine + P65 siRNA group. The ability of cell proliferation was analyzed by MTT; the expression of NF-kappaB P65 and the apoptosis related proteins were examined by Western blot assay; the apoptosis was evaluated by the flow cytometry and laser scanning confocal microscopy analysis stained with Annexin V-FITC/PI; the DNA binding activity of NF-kappaB was examined by electrophoretic mobility shift assay. BxPC-3 cells were injected subcutaneously into nude mice to establish pancreatic xenograft tumors. The tumor volume was monitored and TUNEL assay was used to assess the apoptosis index in tumor tissue after treatment. RESULTS: At 72 h after transfection, the combination with gemcitabine and p65 siRNA significantly decreased the cell viability index (P < 0.05), and down-regulated the expression of Bcl-2 and procaspase-3 and up-regulated the expression of Bax compared with other groups. The combined treatment significantly increased the rate of apoptosis compared with other groups (P < 0.05). EMSA assay indicated that the DNA binding activity of NF-kappaB significantly decreased in NF-kappaB P65 siRNA group and gemcitabine+P65 siRNA group compared with Control group. The combined therapy inhibited the growth of pancreatic xenograft tumors by apoptosis induction in nude mice (P < 0.01). CONCLUSIONS: The effect of gemcitabine inducing cell apoptosis may be potentiated through inhibiting the DNA binding activity of NF kappaB and regulating the expression of apoptosis related proteins by NF-kappaB P65 siRNA, which can activate the mitochondria apoptosis pathway in pancreatic cancer in vitro and in vivo. PMID- 20302734 TI - [Expression and its significance of retinoic acid receptor-beta in colorectal cancer]. AB - OBJECTIVE: To investigate the expression and its significance of retinoic acid receptor-beta (RAR-beta) in colorectal cancer. METHODS: RAR-beta was detected by immunohistochemistry methods and carcino-embryonic antigen (CEA) was tested by chemiluminescence immunoassay methods in normal tissues, paracancerous tissues and colorectal cancer tissues of 60 patients with colorectal cancer treated from January 2006 to January 2007. Above-mentioned data, together with the clinicopathological data of these 60 patients, were analyzed to figure out the expression and its significance of RAR-beta in colorectal cancer. RESULTS: The expression rate of RAR-beta in tumor tissues (48%) was significantly lower than those in both normal tissues (87%) and paracancerous tissues (87%) (P < 0.05). And its expression was also significant lower in patients with lymph node metastasis (32%) and patients with advanced cancer (TNM stage III and IV) (29%) than in those without lymph nodes metastasis (60%) and those with early stage cancer (stage I and II) (69%). There was no significant differences among well, mildly and poorly differentiated cancer tissues. The CEA level rose in 20 patients, and its rising rate was remarkably higher in patients with lymph node metastasis (48%) and in patients with advanced cancer (52%) than those without lymph node metastasis (23%) and in early stage(14%). CONCLUSIONS: The expression of RAR-beta decreases significantly in cancer tissues in patients with colorectal cancer, which may be related to the carcinogenesis of colorectal cancer; and its decreasing degree is correlated negatively with the lymph node metastasis and advanced clinicopathological stage. The expression level of RAR-beta may be a new prognostic indication of patients with colorectal cancer. PMID- 20302735 TI - [The effects of the autologous venous external stents on intimal hyperplasia of the vein grafts in rabbits]. AB - OBJECTIVE: To assess the effect of the autologous venous external stents on intimal hyperplasia of the vein grafts in rabbits. METHODS: Thirty-six male New Zealand white rabbits, aged 5 months and weighing 2.8 to 3.0 kg, were randomly divided into 3 groups: group A, group B and group C, with 12 rabbits in each group. First, a section about 6 cm long of vein was cut from the right external jugular vein of each rabbit and severed to have 3 equal-length segments. Next, each distal segment prepared for anastomosis. The proximal segment invaginating middle segment in group A and only middle segment in group B were used for the external stent. Later, the left common carotid artery was separated from surrounding tissue, from it a section about 0.5 cm long was cut away. Finally, the vein graft was inverted and end-to-end anastomosed to the two ends of the artery with a 9-0 suture. After bloodstream re-established, the diameter of each vein graft was measured. At 2 and 4 weeks postoperative, the graft veins were cut off and histologically examined by the means of HE staining and Masson staining. The smooth muscle cells (SMC) proliferation was studied by the immunohistochemical detection of proliferating cell nuclear antigen. RESULTS: After bloodstream re-established, the diameters of vein graft of group A and group B and group C were (1.6 +/- 0.3) mm, (2.2 +/- 0.4) mm and (2.6 +/- 0.6) mm respectively (P < 0.05). At 4 weeks postoperative, the data of the ratio of intima to media thickness and the index of the proliferating cells of the intima were as follow: group A (1.01 +/- 0.07 and 6.84 +/- 1.98), group B (1.32 +/- 0.08 and 11.01 +/- 2.61), group C (1.55 +/- 0.03 and 14.96 +/- 4.14). Both the data of group A were obviously less than that in group B, and that of group B was less than group C (P < 0.05). CONCLUSION: The autologous venous two-layer external stents inhibit intimal hyperplasia of the vein grafts. PMID- 20302736 TI - [Effect of diazoxide on oxygen free radicals and cell apoptosis in brain tissue after deep hypothermia cerebral ischemia reperfusion injury in young rats]. AB - OBJECTIVE: To determine the effects of diazoxide on oxygen free radicals and cell apoptosis in brain tissue after deep hypothermia cerebral ischemia reperfusion injury in young rats. METHODS: Fifty-four 3-week-old Sprague-Dawley rats were randomly and equitably divided into sham-operated group, model group and diazoxide group respectively (n = 18). The model of hypothermia cerebral ischemia reperfusion injury was made. After 24 hours of operation, the brains of rats were removed and preserved. The content of superoxide dismutase (SOD) and malonaldehyde (MDA) in brain tissue were detected. Cytosolic C release of cytochrome was confirmed by Western Blot. The protein expression of Caspase-3 was determined by immunohistochemistry. RESULTS: In the model group, the content of SOD was (198 +/- 41) U/mg, lower than the sham-operated group's (321 +/- 36) U/mg (P < 0.01). The content of MDA was (212 +/- 21) nmol/mg, was higher than the sham operated group's (100 +/- 23) nmol/mg (P < 0.01), and the expressions of cytochrome C (0.72 +/- 0.09) and Caspase-3 (83 +/- 10) were all significantly higher than those in the sham-operated group (0.17 +/- 0.02 and 115 +/- 9) (P < 0.01). Compared with the model group, the content of SOD in the diazoxide group [(264 +/- 34) U/mg] was markedly increased (P < 0.05). In addition, diazoxide provided significant reductions in the content of MDA [(174 +/- 19) nmol/mg] and the expressions of cytochrome C (0.41 +/- 0.05) and Caspase-3 (99 +/- 11) (P < 0.05). CONCLUSIONS: The neuroprotective effects of diazoxide against brain injury induced by deep hypothermia cerebral ischemia reperfusion through inhibiting oxygen free radicals and cell apoptosis. Diazoxide may become a new neuroprotective drug after infant complicated congenital cardiac operation. PMID- 20302745 TI - [Clinical analysis of 45 cases with pulmonary thromboembolism after surgical procedures]. AB - OBJECTIVE: To analyze the occurrence of pulmonary thromboembolism (PTE) after surgical procedures to attract more attention to the prevention, diagnosis and treatment of this disease. METHODS: Retrospectively analyze the clinical data of the hospitalized patients with post-surgical PTE from June 2004 to February 2009. The average age of the 45 cases was (60 +/- 16) years old, 35 cases received anticoagulant therapy and 6 cases received thrombolytic therapy, the other 4 cases only received emergency medical treatment. Analyze the data about the surgery category, duration, anaesthetic way, risk factors, clinical symptoms, auxiliary examinations, diagnosis, treatment and turnover of these patients. RESULTS: Among the total 45 cases of post-surgical PTE, 37 cases (82.2%) occurred within 2 weeks, it accounted for 13.2% (45/341) of the hospitalized PTE patients during that period. PTE was often seen in patients after major surgical operation such as general (35.6%), gynecological (13.3%), orthopedic (13.3%) and chest surgery, especially the surgery related to malignant tumor (57.8%). The average surgical duration was (220 +/- 124) min, 37 cases (82.2%) was given general anaesthesia. The clinical manifestations and auxiliary examinations results of post-surgical PTE were not typical. Thirty-six cases improved after treatment, 9 cases died and the case fatality ratio was 20.0% (9/45). CONCLUSIONS: Surgical procedure is an important risk factor of PTE. The prevention diagnosis and treatment of post-surgical PTE should be paid more attention to. PMID- 20302746 TI - [Diagnosis and treatment of 193 cases under 45 years old with peripheral arterial disease]. AB - OBJECTIVE: To analyze the etiology, characteristics, and treatment outcomes of peripheral arterial disease (PAD) in patients under 45 years old. METHODS: One hundred and ninety-three cases under 45 years old with PAD were included from January 1999 to January 2009. The demography, etiology, surgical data, treatment outcomes of these patients were evaluated and analyzed. Among these patients, males are 171 cases. The age was 13 to 44 years old (average age 35 years old) and the average time between onsets of PAD to admission was 3.6 months. In the 138 patients who underwent surgical interventions, 30 patients had serologically proven thrombophilia, 50 patients without thrombophilia had other definite reasons but not Burger's disease. A total of 116 cases underwent open operations, 17 cases were received endovascular interventions and 5 cases underwent combinative treatments. RESULTS: Among the 193 patients, 140 cases (72.5%) had definite reasons. Forty patients (28.6%) were diagnosed with congenital or acquired hypercoagulability in the 140 cases. The thrombophilia group had poorer primary patency (70.0% vs. 92.0%, P = 0.010) and secondary patency (83.3% vs. 98.0%, P = 0.016) than non-thrombophilia group and more likely to underwent second revascularization because of recurrent thrombosis within 30 days after operations. After 16 months follow-up, the patients with thrombophilia had lower primary patency (65.0% vs. 75.7%, P = 0.392) and secondary patency (80.0% vs. 91.9%, P = 0.192) than the ones without thrombophilia and the rate of amputation was higher in thrombophilia group (15.0% vs. 5.4%, P = 0.222) but, these didn't achieve statistical significance. CONCLUSIONS: A high prevalence rate of thrombophilia is found in patients less than 45 years old with PAD requiring revascularization. Thrombophilia may have contributed to early postoperative thrombosis of the vascular procedure. So the screening and medical therapy to thrombophilia in young adults with PAD should be reinforced before surgical treatment. PMID- 20302747 TI - [Single-stage replacement of total aorta for type I dissection with renal failure]. AB - OBJECTIVE: To investigate the feasibility of one-stage replacement of total aorta for patient with renal failure. METHODS: The patient was male, 43 years old. The type I aortic dissection was secondary to type III aortic dissection 4 months after endovascular treatment of descending aorta using stented graft 1 year ago. All important branches from aorta were irrigated by false lumen of dissection except left renal artery. The patient has been dialyzed because of renal failure before 5 months with low platelets. Single-stage replacement of total aorta from ascending aorta to iliac artery was successful under deep hypothermia and cardiopulmonary bypass. The operation lasted 12 h. Blood loss during operation was 9000 ml and infusion of blood and blood plasma 7300 ml (including 1500 ml of blood retrieval) and blood platelet 800 ml. RESULTS: Autonomic activity of four limbs was recovered 2 d after operation, and mind recovered 4 d after surgery. The intubation of trachea was extracted 1 week after operation. Re-check through CT showed all vascular prostheses and reconstructed visceral arteries and intercostal arteries were patent though no recovery of renal function. CONCLUSION: One-stage replacement of total aorta for patient with renal failure is feasible. PMID- 20302748 TI - [Influence of preoperative thoracic kyphosis on the sagittal profile of the lumbar spine in idiopathic thoracic scoliosis following selective thoracic fusion]. AB - OBJECTIVE: To analyze the influence of thoracic kyphosis on the sagittal compensatory mode of the spine in idiopathic thoracic scoliosis after the selective thoracic fusion. METHODS: Ninety AIS patients (mean age 14.5 years old) who received selective thoracic fusion from February 1999 to December 2005 in one institution with at least 24-month follow-up were evaluated. Forty-one patients underwent anterior spinal fusion and forty-nine patients underwent posterior spinal fusion. And then the patients were divided into two subgroups according to the magnitude of preoperative thoracic kyphosis (TK): Group A, TK less than 10 degrees ; and Group B, TK more than 10 degrees . The radiological parameters were measured including: thoracic and lumbar curve magnitude, TK, lumbar lordosis (LL), thoracolumbar junction kyphosis (T(10)-L(2), TJK), distal junctional kyphosis (DJK), sagittal vertical axis (SVA). RESULTS: At final follow-up, TK, TJK and DJK increased significantly compared with preoperative Cobb angle in subgroup A patients who underwent anterior spinal fusion (P < 0.05). Generally, there was a lordosis loss of TJK and DJK during follow-up. While in subgroup B, TJK at final follow-up increased apparently compared with preoperative Cobb angle (P < 0.05). And there was a increased trend of DJK in spite of no significant difference, however, there was no obvious change of TK in subgroup B. At the final follow-up, TK and TJK increased significantly in subgroup A patients who underwent posterior spinal fusion (P < 0.05). And there was a increased tendency of DJK during follow-up, although there was no significant difference. And there was no obvious change of TK, TJK and DJK in subgroup B. There was a increased trend of LL in spite of no significant difference in group A patients who underwent anterior or posterior spinal fusion. The sagittal balance maintained well during follow-up in both groups. CONCLUSIONS: For AIS patients with thoracic hypokyphosis, normal TK and LL could be achieved during follow-up with selective thoracic instrumentation. However, the increase of DJK and TJK may occur during the follow-up, and the risk factors may be the anterior short segmental fusion and the reconstruction of the sagittal profile in the hypokyphosis patients. PMID- 20302749 TI - [Surgical treatment of multilevel lumbar degenerative spondylolisthesis]. AB - OBJECTIVE: To discuss the surgical treatment of multilevel lumbar degenerative spondylolisthesis. METHODS: From March 2005 to September 2008, 25 cases of multilevel lumbar degenerative spondylolisthesis were treated with total laminectomy, reduction of spondylolisthesis and 360 degrees circumferential fusion through interbody (PLIF), transverse process (PLF) and pedicle screw fixation. All cases were followed up for 0.5 - 4 years. The Lenke grading system was used to assess the spinal fusion and Henderson grading system was used to assess the clinical outcomes. RESULTS: Complete reduction of spondylolisthesis was achieved in all cases. The bone fusion was grade A in 23 cases, grade B in 2 cases. The clinical outcome was excellent in 16 cases, good in 6 cases and poor in 3 cases. CONCLUSIONS: The pathogenesis of lumbar degenerative multilevel spondylolisthesis is different from that of single-level spondylolisthesis. Complete decompression, reduction of spondylolisthesis sufficient fusion and reliable pedicle screw fixation can provide successful interbody fusion and satisfactory clinical results.It's crucial to reduce multilevel spondylolisthesis by proper techniques based on different types of listhesis. PMID- 20302750 TI - [Indication of fusion for degenerative lumbar spinal stenosis treated by "windows technique" laminoforaminotomy]. AB - OBJECTIVE: To explore the indications of fusion for degenerative lumbar spinal stenosis treated by "windows technique". METHODS: From December 1999 to December 2005, 145 consecutive patients who were treated by primary decompression with "windows technique" laminoforaminotomy for degenerative lumbar spinal stenosis, a retrospective study, were divided into 3 groups (A and B and C) by preoperative lumbar conditions and surgical methods. In group A, 39 patients with spinal instability or degenerative lumbar spondylolisthesis or scoliosis underwent decompression and fusion; in group B, 31 patients with spinal instability or degenerative lumbar spondylolisthesis or scoliosis underwent decompression alone; In group C, 75 patients without spinal instability or degenerative lumbar spondylolisthesis or scoliosis were treated by decompression without fusion. On hospital medical records to review, they were followed up by telephone and out patient referral. Statistics the duration of hospitalization, operative time, estimated blood loss; Observed recrudescence and reoperation and complication; and using Oswestry Disability Index and Visual Analog Scale and satisfaction rate for efficacy assessment, application SPSS 13.0 software. RESULTS: All 145 patients had at least a 3-year follow-up (ranging 37 to 108 months). In the group C, the duration of hospitalization less than in the group A or B (P < 0.05); In the group A, the operative time and estimated blood loss greater than in the group B or C (P < 0.05); The group B treated by decompression alone in the presence of instability or spondylolisthesis or scoliosis showed the worst results by the Oswestry Disability Index or Visual Analog Scale or ate of satisfaction (P < 0.05). The same good results can be obtained in the group A and C. There were not different about recrudescence or reoperation or complication in the three groups. CONCLUSIONS: Fusion should be performed on patients with instability or degenerative lumbar spondylolisthesis or scoliosis after primary decompression with "windows technique" laminoforaminotomy. The patient with simple lumbar spinal stenosis undergone primary surgery does not require fusion. PMID- 20302751 TI - [The clinical study of reconstruction of traumatic brachial plexus root avulsion injury in children]. AB - OBJECTIVE: To observe the primary result of finger flexion reconstruction in the procedure of direct anastomosis of contralateral C(7) transferred through the prespinal route with lower trunk in children suffered traumatic brachial plexus root avulsion injury. METHODS: On the healthy side, the C(7) nerve root was identified anatomically and transected at the level of division by dissecting its anterior and posterior division as far distal as possible up to the level where the nerve fibers interweaving with other division, then the contralateral C(7) nerve root was dissected proximally up to the neuroforamina. The contralateral C(7) nerve root was transferred to contralateral side through the prespinal route. The entire brachial plexus of suffered side was exposed through the union incision superior and inferior to the clavicle, The lower trunk was identified and dissected proximally to the C(8) and T(1) nerve root which were severed at the lateral margin of anterior scalenus, and then the dorsal division and anterior medial pectoral nerve of lower trunk were severed. The median nerve, ulnar nerve and medial antebrachial cutaneous nerve were identified from the origin and dissected distally continue to the midpoint of upper arm, and lateral head of the median nerve was severed so that the lower trunk, medial cord and median nerve, ulnar nerve and medial antebrachial cutaneous nerve can be fully mobilized. Anteriorly flexion and adduction of the should at 0 degrees and flexion elbow at 90 degrees , this could allow considerable length to be gained when pulling the lower trunk proximally, direct anastomosis of contralateral C(7) with lower trunk was performed. If there was any tension exist, the appropriate humerus shorten osteotomy should be performed. From August 2004 to December 2008, 20 children including 13 cases with total brachial plexus nerve root avulsion injury and 7 cases with middle and lower trunk avulsion injury were repaired by this procedure. Twenty cases including 16 males and 4 females, the average age was 13 years with a range of 5 to 18 years. The interval from injury to operation ranged 1 to 11 months with a mean of 4.6 months. Eleven patients were performed the humeral shorten osteotomy, the length of the humeral shorten was 2.0 - 4.5 cm, with the mean of (3.1 +/- 0.7) cm. RESULTS: The follow up period was 12 to 51 months, with the average of 26 months. The muscle strength of finger flexion attained M 4 in 18 cases, M 2 in 2 cases. The motor function of thumb flexion gained M 4 in 10 cases, M 3 in 8 cases, M2 in 2 cases. Of the 2 cases achieved motor function of intrinsic muscles of the hand of M3. CONCLUSIONS: The direct anastomosis of contralateral C(7) with lower trunk in children with traumatic brachial plexus avulsion injury can improve the effect of reconstructing the function of finger flexion because it reduces one never anastomosis site and decreases the distance of nerve regeneration compared with the traditional method. With this modified procedure, the functional recovery of intrinsic muscles of the hand in children with traumatic brachial plexus avulsion injury is becoming possible. PMID- 20302752 TI - [Estimated glomerular filtration rate as a risk factor for long-term survival in Chinese renal insufficiency patients after isolated coronary artery bypass graft surgery]. AB - OBJECTIVE: To investigate the eGFR as a risk factor for long-term (4-year) outcome in Chinese renal insufficiency patients after isolated coronary artery bypass grafting (CABG) at our institution. METHODS: From January 1999 to September 2003, 3371 consecutive patients who underwent isolated CABG were retrospectively reviewed. Of these patients, 549 (16.29%) patients were female, 1979 (58.71%) patients with hypertension, 866 (25.69%) patients with diabetes, 1130 (33.52%) patients with hyperlipidemia, 1011 (29.99%) patients with left main stenosis > 50%, and 1150 (34.11%) patients undergoing off-pump procedures. The mean age was (60 +/- 9) years old. Estimated GFR was calculated using the Cockcroft-Gault formula. The main outcomes were in-hospital mortality, in hospital morbidity and long-term mortality. COX analysis was used in this study. RESULTS: There were 649 patients with glomerular filtration rate estimates < 60 ml/(min.1.73 m(2)) and 2722 patients with glomerular filtration rate estimates > 60 ml/(min.1.73 m(2)). The in-hospital mortality and follow-up mortality was higher in the estimated glomerular filtration rate < 60 ml/(min.1.73 m(2)) group (2.77% vs. 0.77%, P < 0.01), (6.81% vs. 2.63%, P < 0.01). The COX analysis result confirmed eGFR < 60 ml/(min.1.73 m(2)), derived using the Cockcroft-Gault formula (HR: 1.948, 95%CI: 1.357 to 2.797, P < 0.01) was an independent risk factor for long-term mortality in patients after coronary artery bypass grafting surgery. CONCLUSIONS: The estimated glomerular filtration rate < 60 ml/(min.1.73 m(2)) derived using the Cockcroft-Gault formula is an independent risk factor for long term mortality in patients after coronary artery bypass grafting surgery. PMID- 20302753 TI - [An ex vivo study on the vaporization ratio of the prostatic tissue lased by the 2 micron laser]. AB - OBJECTIVES: To observe the vaporesection efficiency of the 2 micron laser to the prostatic gland in benign prostatic hyperplasia, and investigate the method of estimating the amount of the vaporesected prostatic tissues during transurethral vaporesection of the prostate using the 2 micron laser system in the treatment of benign prostatic hyperplasia. METHODS: Total 9 fresh prostatic gland specimens were obtained from patients with BPH under open surgical procedures, and vaporesected under a simulated transurethral environment with the 2 micron laser system immediately after weighted. Energies and time consumptions were noted, collections of vaporesected tissue specimens and the remnants of the prostatic glands were weighted after the procedures. The ratios of the vaporized tissues and the collected tissues to the whole vaporesected tissues were calculated respectively. The vaporesection efficiency of the 2 micron laser to the prostatic tissues was also calculated. RESULTS: Among the total lost tissues, about (65.6 +/- 1.5) percent of which were that of vaporized, and nearly (34.5 +/- 1.5) percent were resected. Linear correlation between the weight of collected prostatic tissue(x) and the weight of prostatic gland specimens(y) could be defined as a formula of [y = 3.245x - 6.475 (t = 15.097, P = 0.000)]. CONCLUSION: The amounts of the whole prostatic tissues removed by the 2 micron laser could be calculated from the collected resected prostatic specimens under a simulated transurethral surgical procedure. PMID- 20302754 TI - [Experience of the diagnosis and treatment of primary small intestine lymphoma]. AB - OBJECTIVE: To report the experiences of the diagnosis and treatment of primary lymphoma of the small intestine (PSIL). METHODS: The clinical data of 15 patients with PSIL treated from January 2003 to July 2007 was investigated retrospectively. Of the 15 cases, 9 patients were male and 6 were female, the average age was 51.6 years (range, 18 - 73 years). Data of gender, age, clinical manifestation, laboratory examination, imageology examination, diagnosis and treatment of the patients was reviewed. RESULTS: The most common clinical manifestations were as follow: abdominal pain, abdominal lump, bowel obstruction, gastrointestinal hemorrhage and athrepsy. Serum tumor markers were checked normal. All the 15 cases were found with tumor by spiral CT, and 12 cases were diagnosed as PSIL. Eleven cases were given Ba-meal examinations, and positive results was found in 4 cases, and only 1 case was considered to be PSIL. All the 15 patients received operation. All the patients were diagnosed as non-Hodgkin lymphoma (NHL) by postoperative pathology (8 patients as diffuse large B-cell lymphoma, 5 as mucosa associated lymphoid tissue type B cell lymphoma and 2 as enteropathy-type intestinal T cell lymphoma). No perioperative death occurred. Ten patients received adjuvant chemotherapy with the regimen of CHOP (cyclophosphamide + epirubicin + vincristine + prednisone) after the operation. Fourteen cases were followed-up for a mean time of 30 months (range, 6 - 52 months). The 1- and 3-years survival rate was 85.7% and 57.1%, respectively. CONCLUSIONS: PSIL has no specific clinical manifestations, the diagnostic rate with barium study is low, spiral CT scan is a promising diagnostic method for PSIL. Operation combined with chemotherapy is important for PSIL. PMID- 20302755 TI - [Morphologic and functional characteristics of the immortalized human liver sinusoidal endothelial cell line]. AB - OBJECTIVE: To investigate the morphologic and functional characteristics of the immortalized human liver sinusoidal endothelial cell line (LSEC line). METHODS: Immunofluorescence staining and fluorescence microscopy were used to detect the classic endothelial cell markers in LSEC line, and flow cytometry was used to analyze the purity of the human LSEC line. The morphology (including W-P bodies and surface fenestrations) and phagocytotic capacity of the human LSEC line were observed by transmission and scanning electron microscope. The proliferation curve of the human LSEC line was analyzed by MTT assay. The functional differences between the human LSEC line and human primary LSEC in expression of ELAM-1 and ICAM-1, activities of fibrinolysis (PAI-1, t-PA, u-PA), releasing of IL-6 and IL-8 were compared respectively by enzyme linked immunosorbent assay. Comparison of the susceptibility to hypoxia-reoxygenation induced apoptosis between the human LSEC line and human primary LSEC were investigated by TUNEL. RESULTS: The established human LSEC line maintained a high proliferative ability and has been passaged for more than 80 times in the absence of any growth factors. Immunofluorescence staining showed that the human LSEC line could express classic endothelial cell marks including von Willebrand Factor (vWF), and could take up acetylated low-density lipoproteins (Ac-LDL). The purity of the human LSEC line was confirmed over 95% by flow cytometric analysis. The W-P bodies and the phagocytosis of Dynabeads was demonstrated by transmission electron microscope. And fenestrations could be found cellular surface with scanning electron microscopy. When compared with human primary LSEC, the human LSEC line has an equivalent responsiveness to tumor necrosis factor in up regulation of ELAM-1 and ICAM-1. The human LSEC line can also release PAI-1, t PA, u-PA but can not release IL-6 and IL-8 to TNF-alpha. In contrast, human primary LSEC could release IL-6. The human LSEC line showed higher susceptibility to hypoxia-reoxygenation-induced apoptosis, and the percentage of apoptotic cells was as high as (38.4 +/- 6.7)%, while (28.6 +/- 4.5)% and (7.8 +/- 1.2)% respectively in primary LSEC and in human umbilical vein endothelial cells. CONCLUSIONS: The established human LSEC line maintains the special phenotypes and the major functional characteristics, and especially maintains the high susceptibility to hypoxia-reoxygenation-induced apoptosis. Therefore it is feasible to use this cell line for the study of liver ischemia-reperfusion injury. PMID- 20302756 TI - [Expression of EphA7 protein in primary hepatocellular carcinoma and its clinical significance]. AB - OBJECTIVE: To investigate the expression and clinical significance of EphA7 protein in primary hepatocellular carcinoma. METHODS: Immunohistochemistry and Western blot were used to detect the expression of EphA7 protein in 40 cases of primary hepatocellular carcinoma, their corresponding adjacent liver tissues and 10 cases of normal liver tissues. The relations with its clinical pathological parameters were analyzed too. RESULTS: Expression of EphA7 protein was mainly located in the cytoplasm and the blood vessels of the septa, which was found in hepatocellular carcinoma tissues, their corresponding adjacent liver tissues and normal liver tissues. Western blot analysis showed that the expression level of EphA7 protein in hepatocellular carcinoma (0.58 +/- 0.26) was greater than that in corresponding adjacent liver tissues (0.40 +/- 0.22, P < 0.05) and normal liver tissues (0.32 +/- 0.16, P < 0.05). But it had no significant difference between corresponding adjacent liver tissues and normal liver tissues (P > 0.05). EphA7 protein expression was correlated with histological differentiation, tumor thrombi in portal vein, lymph node metastasis and high AFP level (P < 0.05). CONCLUSIONS: EphA7 protein expression is significantly correlated with the biological behavior of primary hepatocellular carcinoma. The high expression of EphA7 protein may play an important role in the malignancy transformation, invasion progression and metastasis of primary hepatocellular carcinoma. PMID- 20302758 TI - [Protective role of MMP-9 inhibitor batimastat in acute lung injury after cardiopulmonary bypass]. AB - OBJECTIVE: To investigate the protective effect of exogenous inhibitor of matrix metalloproteinases-9 (MMP-9), batimastat, in the lung injury induced by cardiopulmonary bypass (CPB) in dogs. METHODS: Thirty healthy mongrel puppies were randomly divided into 3 groups: control group, low-dose group [batimastat 10 mg/(kg.d) for 3 days before operation] and high-dose group [batimastat 30 mg/(kg.d) for 3 days before operation]. The off-pump puppies' model of acute lung injury was established, and hemodynamic and respiratory parameters were monitored. The preoperative and postoperative alveolar-arterial oxygen difference (A-aDO(2)) and respiratory index (RI) were calculated. From the beginning of surgery, blood samples were taken at the time 0, 60, 120, and 270 min. Plasma concentrations of MMP-9 were measured by ELISA, and blood MMP-9 mRNA expressions were determined by RT-PCR. The myeloperoxidase (MPO) activity of centrifugal bronchoalveolar lavage fluid were measured by Colorimetry. And MMP-9 activity was determined by Gelatin zymography. Light and electronic microscope were used to observe the morphological changes of lung tissue. A small piece of left lung tissue was taken, weighed and baked to calculate the wet weight (W/D) index. RESULTS: After cardiopulmonary bypass, the concentrations of MMP-9 and mRNA expressions of the control group were increased significantly, and lung injury was apparent. At 270 min, the MMP-9 plasma concentration of high-dose group (17.36 +/- 1.18) microg/L was significant reducing than control group (30.47 +/- 2.22) microg/L (P < 0.05). After operation, A-aDO(2) and RI of high-dose group were significantly improved than control group (P < 0.05). The W/D index of the high-dose group (2.8 +/- 0.48) was significantly lower than that of control group (4.7 +/- 0.6) (P < 0.05). And the pathological changes of lung tissue were significantly improved in the high-dose group. However, there was no significant difference in the MMP-9 mRNA expression in three groups. CONCLUSIONS: Batimastat plays a role in the protection of the lung injury of CBP by reducing the concentration and activity of MMP-9, the degradation of the cell membrane and pulmonary neutrophil infiltration and reduction of pulmonary edema. PMID- 20302759 TI - [Study on the effect of CD4+CD25+ regulatory T cell adoptive transfusion on humoral immune function in rat composite tissue allotransplantation model]. AB - OBJECTIVE: To approach the effect of the donor antigenic specificity CD4+CD25+ regulatory T cell (Treg) on cellular immune tolerance function in rat composite tissue allotransplantation (CTA). METHODS: Use the method of immunomagnetic beads to separate CD4+CD25+ Treg, (1 x 10(6))CD4+CD25+ Treg was transfused to rat CTA model. Collected peripheral blood 30 days after operation, and used nylon wool column to separate B cell and T cell. With the stimulation of IgM, detected B cell proliferation and the level of IgG and IgA in serum. Observed the effect of CD4+CD25+ Treg on B cell and T cell function and the survival of allotransplants, and analyzed the data by statistics. RESULTS: The purity of separated CD4+CD25+ Treg was 95.6%. The CPM of T cell of normal control group, topical intervention group, systemic intervention group and non-intervention group were (2436 +/- 358), (2273 +/- 136), (2338 +/- 228) and (3749 +/- 245). The CPM of B cells of normal control group, topical intervention group, systemic intervention group and non-intervention group were (2418 +/- 348), (2252 +/- 127), (2315 +/- 218) and (3720 +/- 224), there was a significant difference in these groups (P < 0.01). The serum level of IgG and IgA of topical intervention group and systemic intervention group were (12.56 +/- 1.30), (2.38 +/- 0.21), (13.48 +/- 1.23) and (2.86 +/- 0.24) g/L, and of normal control group was (12.35 +/- 1.28), (2.36 +/- 0.12) g/L, had no significant difference (P > 0.05). But Treg of non-intervention group was (16.58 +/- 1.12), (3.75 +/- 0.37) g/L, there was a significant difference in the non-intervention group and the three above groups (P < 0.01). The survival time of CTA in intervention of local and systemic groups were (97 +/ 13) and (63 +/- 10) d, which were significant longer than the non-intervention group [(22 +/- 8) d, P < 0.01]. CONCLUSIONS: Donor antigen specific CD4+CD25+ Treg has significantly inhibited B cell and T cell function. It can induce immune tolerance and extend the survival time of CTA; as well local application is better than systemic. PMID- 20302766 TI - [FLT3 gene mutation and its prognostic implication in patients with acute leukemia.]. AB - OBJECTIVE: To evaluate the prevalence of FLT3 mutation in different subtypes of acute leukemia (AL) patients diagnosed by WHO criteria and its significance in prognosis. METHODS: Polymerase chain reaction (PCR) was used to detect internal tandem duplication of FLT3 gene (FLT3-ITD) and D835 mutation in 468 firstly diagnosed AL patients and analyzed their prognosis by Kaplan-Meier and log-rank test. RESULTS: In 468 AL patients, there were 374 acute myeloid leukemia (AML) cases (79.9%) and 83 acute lymphoblastic leukemia (ALL) cases (17.7%). In AML patients, FLT3-ITD mutation was present in 59 cases (15.9%) while D835 mutation in 15 cases (4.0%); and in ALL patients, none for FLT3-ITD while D835 mutation in 2 cases (2.4%). FLT3-ITD mutation might adversely affect clinical outcome in AML patients (excluding APL) with a lower CR rate (52.3% vs 71.2%) and a shorter median survival (9 months vs 18 months). For APL FLT3-ITD mutation had no effect on CR rate, but with a shorter DFS and OS. There was no evidence that FLT3-D835 affected the prognosis. CONCLUSION: FLT3 mutation is more frequently present in AML and FLT3-ITD is associated with lower CR rate and shorter median survival time while FLT3-D835 has no such effect. PMID- 20302767 TI - [Clinical features and prognosis of acute myeloid leukemia-M(4).]. AB - OBJECTIVE: To investigate factors that affect survival and prognosis of acute myeloid leukemia (AML)-M(4). METHODS: Seventy AML-M(4) patients were divided into three groups, neither eosinophilia nor inv(16)?[Eos(-)?], eosinophilia with inv (16)?[Eos(+) inv(16)(+)?], and eosinophilia with no inv(16)?[Eos(+) inv(16)(-)?]. Clinical features, immunophenotype, chromosome karyotype, overall survival (OS) and relapse-free survival (RFS) were analyzed. RESULTS: The total complete remssion (CR) rate was 85.7%, CR rate after the first course of induction therapy was 71.4%. The median OS was 20 (1.2 - 162.4) months, and median RFS 78.0 (1.2 - 129.5) months. The 3 and 5 year OS rates were 42% and 42%, and 3 and 5 year RFS rates were 59% and 54%, respectively. The CR rate, CR after the first course of induction therapy and the median OS for the Eos(-) group were 76.9%, 61.5% and 11.2 (1.2 - 162.4) months; for the Eos(+) group were 96.8%, 89.6% and did not reach; for the Eos(+)inv16(+) group were 100%, 94.4% and did not reach; and for the Eos(+) inv(16)(-) group were 91.7%,69.2% and 14.3 months respectively. The statistical assay showed significant difference between Eos(+)inv(16)(-) and Eos(+)inv(16)(+) groups in OS. The Eos(+) patients present with early onset and low count of platelets. CONCLUSION: Eosinophilia emerged as a favorable prognostic factor, and the concomitant presence of both eosinophilia and inv(16) is associated with a significantly favorlable prognosis. PMID- 20302769 TI - [In Process Citation]. PMID- 20302768 TI - [Nilotinib treatment for imatinib resistant or intolerant chronic myelogenous leukemia.]. AB - OBJECTIVE: To evaluate the safety and efficacy of nilotinib in chronic myelogenous leukemia (CML) patients with resistance or intolerance to imatinib. METHODS: Thirty-five CML patients after imatinib failure or intolerance received oral administration of 400 mg nilotinib twice daily. The overall survival, hematologic and cytogenetic responses, as well as adverse events were evaluated. RESULTS: The median duration of nilotinib therapy was 11 (1 - 23) months, with a median follow-up of 19 months. Nonhematologic adverse events were mostly of grade 1-2. The most common ones possibly related to nilotinib were increase of bilirubin (76%) and rash (46%). Grade 3-4 hematologic adverse events includes thrombocytopenia (37%), neutropenia (26%) and anemia (26%). Nilotinib was proved to be well-tolerated in this study. Grade 3-4 hematologic adverse events happened more frequently in advanced phase CML. The rate of major cytogenetic response in chronic phase (CP) CML was much higher than those in advanced CML (38.5% vs 22.2%). The median time to major cytogenetic response was 3 months. The estimated overall survival at 18 months was (93.5 +/- 1.0)%. CONCLUSION: Nilotinib is a more effective and safe treatment option for imatinib-resistant or -intolerant CML-CP patients. PMID- 20302770 TI - [A clinical and laboratory study of TCF3-PBX1 positive adult acute lymphoblastic leukemia.]. AB - OBJECTIVE: To explore the morphology, immunophenotype, cytogenetics and clinical features of TCF3-PBX1 fusion gene positive adult acute lymphoblastic leukemia (ALL). METHODS: R banding was used to analyze conventional cytogenetics (CC), interphase fluorescence in situ hybridization (iFISH) and RT-PCR to detect the TCF3-PBX1 fusion gene, and flow cytometry to immunophenotype. The clinical and laboratory features and long-term follow-up of the patients were analyzed. RESULTS: The incidence of 19 TCF3-PBX1-positive adult ALL was 3.13% of total ALL patients. Of them, 12 and 7 cases were diagnosed as L(1) and L(2) morphology respectively; 7 cases with balanced translocation of chromosome 1 and 19; 10 with der(19) t(1;19) formed from unbalanced translocation and 2 with normal karyotypes. TCF3-PBX1 fusion gene was detected by RT-PCR in 9 cases, and by iFISH in 17. 16 cases were B-phenotype and the other 2 T-phenotype; 17 cases had lymph node, spleen or liver infiltration. Of 18 patients received chemotherapy, 17 (94.7%) achieved complete remission (CR); the median relapse-free survival (RFS) and median overall survival was 3.2 months and 7.2 months, respectively. CONCLUSIONS: TCF3-PBX1-positive adult ALL had unique clinical and pathological features with high remission rate, high relapse rate and short survival time and should be considered to receive intensified treatment strategies. iFISH combined with CC and RT-PCR can increase the detection rate of t(1;19)/TCF3-PBX1 fusion gene. PMID- 20302771 TI - [In Process Citation]. PMID- 20302772 TI - [An epidemiological survey of acute lymphocytic leukemia from 2002 to 2006 in Shanghai.]. AB - OBJECTIVE: To analyse the epidemiological data of acute lymphoblastic leukemia (ALL) in Shanghai. METHODS: ALL cases in Shanghai from 2002 to 2006 were retrospectively investigated. RESULTS: All together there were 544 newly diagnozed ALL cases. The yearly incidence of ALL was 0.81/10(5), which was slightly higher in men (0.86/10(5)) than in women (0.75/10(5)). The age stratified incidence showed 2.31/10(5) in patients (pts) 60 y. The incidences in Chongming County was 0.60/10(5), being the lowest in all districts. The morphological types of ALL was L(1) (26.2%), L(2) (57.4%) and L(3) (16.4%); the immunophenotype was B (80.1%) and T (19.5%). The incidence of ALL with myeloid antigen expression was 20.2%. Genetic examination revealed that chromosome aberration of t(9;22) was the most common one. CONCLUSIONS: The incidence of ALL in Shanghai is 0.81/10(5). Compared with the national standard (1986 - 1998), the incidence in adolescents is obviously increased. Chongming County has the lowest incidence, indicating a role of environment factor in ALL incidence. PMID- 20302774 TI - [In Process Citation]. PMID- 20302773 TI - [Unexplained multiple effusions as a manifestation of chronic graft-versus-host disease after allogeneic hematopoietic transplantation.]. AB - OBJECTIVE: To analyze the presentations and treatments of unexplained multiple effusions after allogeneic hematopoietic transplantation (allo-HSCT) and their relationships with chronic graft-versus-host disease (cGVHD). METHODS: The data of 1385 allo-HSCT patients from Jan.1999 to Nov. 2008 in our institute were reviewed retrospectively. RESULTS: cGVHD occurred in 911 patients, including 327 (35.8%) limited cGVHD, and 198 (21.7%) extensive cGVHD. Effusions were identified in 28 patients. Nine cases were from infections and two tumor relapses. Cirrhosis and hypoproteinemia caused ascites in 6 patients. The small amount pericardial effusions occurred in 7 patients, which were related to the toxicity of drugs. The remaining 4 patients had large and recurrent sterile effusions involving peritoneal, pericardial, pleural cavities and/or testicular sheath cavity. These 4 cases were all middle aged men and received transplantation from HLA identical siblings. The effusions had an insidious onset and were or were proved to be transudate. Examinations of the effusions for bacteria, virus and yeast were negative. The only diagnoses of the patients were cGVHD. All of the patiants responded to low dose steroid and alive, but only one achieved complete remission. CONCLUSION: The unexplained recurrent multiple effusions after allo HSCT might be a rare manifestation of chronic GVHD. PMID- 20302776 TI - [In Process Citation]. PMID- 20302775 TI - [Expression and function of TRAF1 in Hodgkin's lymphoma cells.]. AB - OBJECTIVE: To investigate the function of tumor necrosis factor receptor associated factor 1 (TRAF1) and CD30-TRAF1 signaling in Hodgkin's lymphoma. METHODS: Endogenous and CD30 ligand-induced TRAF1 expression at mRNA and protein levels were examined by quantitative RT-PCR and Western blot analyses, respectively. RNA interference was performed to silence the expression of TRAF1 in L428 cells and examine its effect on cell survival. ELISA-based NF-kappaB family transcription factor activity assay was performed to quantify the kappaB DNA-binding activity in nuclear extracts. The expression of JunB was measured by Western blot. RESULTS: TRAF1 expression was detected at both mRNA and protein levels in B cell-derived lymphoma cell lines (L428 and KM-H2). CD30 activation via binding to CD30 ligand induced the TRAF1 expression, the relative mRNA expression was increased to 7.26 +/- 0.23 from 3.50 +/- 0.20, the relative protein expression was increased to 4.53 +/- 0.55 from 2.31 +/- 0.35. The apoptosis rate was increased to (27.7 +/- 5.8)% in TRAF1-silenced L428 cells compared to (5.7 +/- 1.2)% in control cells. The p50 and RelA DNA-binding activity were decreased in TRAF1-silenced L428 cells. The expression of JunB upon CD30 ligand stimulation was not changed in TRAF1-silenced L428 cells. CONCLUSIONS: TRAF1 is overexpressed in B cell-derived Hodgkin's lymphoma cells, which is regulated by CD30 signaling pathway. TRAF1 is a crucial molecule mediating the activation of the classical NF-kappaB activity, which further facilitates the anti-apoptosis. PMID- 20302777 TI - [Correlation of Bcl-2 with immunological subtype and prognosis in diffuse large B cell lymphoma.]. AB - OBJECTIVE: To investigate the Bcl-2 protein and gene expression in diffuse large B-cell lymphoma (DLBCL), and analyze its correlation with immunosubtype and prognosis. METHODS: Seventy-three cases of DLBCL were performed immunohistochemistry analysis with a panel of antibodies CD3, CD10, CD20, Bcl-6, Bcl-2 and MUM-1, and classified into germinal center B-cell (GCB) type and non GCB type. Fluorescence in situ hybridization (FISH) was employed to detect bcl-2 gene expression in 57 cases with chromosome translocation t (14;18). RESULTS: The percentages of tumor cells expressed CD10, Bcl-6, MUM-1 and Bcl-2 were 15.1%, 38.4%, 71.2% and 79.2%, respectively. 16 cases (21.9%) were GCB type and the rest (78.1%) were non-GCB type. 16 of 57 cases (28.1%) were t (14; 18), including 5 of GCB type (31.2%) and 11 of non-GCB type (68.2%). The expression of Bcl-2 protein was correlated with immunological subtype (P = 0.035), but not with survival time (P = 0.253). Between the t(14;18) positive and negtive groupes, there was significant difference for survival time (P = 0.022), but no difference for immunological subtype (P = 0.340). There was no correlation between Bcl-2 protein and t(14;18). CONCLUSIONS: GCB type DBLBCL with expression of Bcl-2 protein had a poor prognosis. t(14; 18) positive BLBCL had poor prognosis. The expression of Bcl-2 protein and t(14; 18) are usually discordant. PMID- 20302778 TI - [microRNA-21 and microRNA-30b expression in multiple myeloma.]. AB - OBJECTIVE: To investigate the expression of miR-21 and miR-30b in multiple myeloma (MM). METHODS: Peripheral blood mononuclear cells from patients with MM were cultured at 2.5 x 10(6) cells/ml in alpha-MEM supplemented with 10% of fetal bovine serum, antibiotics, RANKL (50 ng/ml), and macrophage colony-stimulating factor (25 ng/ml) for 10 to 14 days to obtain osteoclasts with bone-resorbing activity. Primary myeloma cells were purified from 12 MM patients. Of them, 8 samples were cocultured with osteoclasts and 4 as noncocultured control. The expression of miR-21 and miR-30b was detected by real-time PCR. RESULTS: The viability of MM cells recovered from cocultures was higher than those of noncocultured control. After cocultured with osteoclasts, primary myeloma cells from eight patients exhibited a 1.3- 5.9-fold increase in miR-21 expression and 1.38- 4.32-fold decrease in miR-30b expression compared with controls. In highly purified plasma cells from 3 healthy subjects, 12 MM patients and 11 MM cell lines, the expression of miR-21 was 1.9 +/- 0.8, 6.5 +/- 4.9 and 35.1 +/- 36.2, respectively; the expression of miR-30b was 13.6 +/- 1.8, 7.2 +/- 6.3 and 4.5 +/- 1.9, respectively. CONCLUSIONS: miR-21 acts as an oncogene and miR-30b a tumor suppressor gene in MM. PMID- 20302780 TI - [In Process Citation]. PMID- 20302779 TI - [Effect of bortezomib and arabinoside on proliferation and apoptosis of K562 cell.]. AB - OBJECTIVE: To investigate the effect of bortezomib (Bor) alone and in combination with arabinoside (Ara-C) on proliferation and apoptosis of leukemia cell line K562. METHODS: K562 cells were treated with 20 nmol/L Bor and 0.2 microg/ml Ara-C alone and in combination for 48 h. MTT was used to study the inhibitory effects on cell growth and the apoptosis rate was analysed by flow cytometry. After K562 cells treated with 20 nmol/L Bor or 0.2 microg/ml Ara-C for 6 h, the activity of NF-kappaB was analyzed by SP immunohistochemistry and cell cycle by flow cytometry. RESULTS: The inhibition and apoptosis rates of K562 cells in combination groups were higher than those in the two single treatment groups (P < 0.01), especially in the combined treatment group in which K562 cells were treated first with Ara-C for 6 h then with Bor combined,the inhibition and apoptosis rates were the highest [(81.5 +/- 4.0)% and (29.2 +/- 3.1)%, respectively] (P < 0.01). In the other two combined groups in which the cells were treated with Bor for 6 h then with Ara-C combined, or treated with the two drugs simultaneously, the inhibition and apoptosis rates were (54.1 +/- 4.2)% and (18.7 +/- 3.5)%, and (66.2 +/- 2.8)% and (21.1 +/- 2.2)%, respectively. Treatment of K562 cells with 20 nmol/L Bor for 6 h, the activity of NF-kappaB was decreased significantly, and the cells were apparently arrested in G(2)/M phase, and treatment with 0.2 microg/ml Ara-C in the same manner, the activity of NF-kappaB was increased significantly, and the cells were apparently arrested in G(1) phase. CONCLUSIONS: Bor can effectively inhibit K562 cell proliferation, and induced its apoptosis. This effect was enhanced significantly when in combination with Ara-C. Pretreatment of K562 cells with Ara-C lead to the increased activity of NF-kappaB and the fraction of G(1) phase cells. PMID- 20302781 TI - [In Process Citation]. PMID- 20302782 TI - [In Process Citation]. PMID- 20302784 TI - [In Process Citation]. PMID- 20302783 TI - [In Process Citation]. PMID- 20302785 TI - [In Process Citation]. PMID- 20302786 TI - [In Process Citation]. PMID- 20302788 TI - [In Process Citation]. PMID- 20302787 TI - [In Process Citation]. PMID- 20302790 TI - [In Process Citation]. PMID- 20302789 TI - [In Process Citation]. PMID- 20302791 TI - [Quantitative monitoring of mononucleated cell Epstein-Barr virus (EBV)-DNA for predicting EBV associated lymphoproliferative disorders after stem cell transplantation.]. AB - OBJECTIVE: To monitor blood cells EBV-DNA copies by quantitative Epstein-Barr virus (EBV) polymerase chain reaction after hematopoietic stem cell transplantation (HSCT) and to evaluate its implication. METHODS: EBV-DNA copies of peripheral blood mononucleated cells (PBMNCs) were detected by fluorescence quantitative PCR once a week since conditioning regimen from fifty one patients received HSCT. Correlation between development of lymphoproliferative disorders (LPD) and EBV-DNA copies and influence factors of EBV reactivation were analyzed. RESULTS: The cumulative incidence of EBV viremia was 58.8%. EBV reactivation occurred (39.6 +/- 23.5) days after HSCT, later than that of cytomegalovirus (CMV) reactivation (25.0 +/- 15.1) days (P < 0.01). HLA mismatch (P < 0.01), use of antithymocyte globulin (ATG) (P < 0.01), age less than twenty (P < 0.001) were factors for EBV reactivation, (93.3% vs 48.1%, 92.3% vs 18.7%, and 100% vs 53.1%, respectively). EBV related post-transplant lymphoproliferative disorders (EBV PTLD) occurred only in 4 out of 30 (13.3%) EBV reactivation patients, whose EBV DNA load maintained over 10(6) copies/ml for at least two weeks (4 out of 13 cases). The median survival time of EBV-PTLD patients was 19.5 (11 - 75) days. CONCLUSIONS: EBV reactivation occurs frequently after HSCT, especially in those received HLA mismatch grafts, used antithymocyte globulin or aged under twenty. Patients with EBV loads over 10(6) copies/ml, especially lasting over two weeks, appear to have an increased risk for PTLD, and pre-emptive therapy may be of clinical useful. PMID- 20302792 TI - [Reduced intensity conditioning regimen for related and unrelated allogeneic peripheral blood hematopoietic stem cell transplantation in chronic myeloid leukemia.]. AB - OBJECTIVE: To evaluate the overall efficacy and transplant-related mortality (TRM) of related and unrelated allogeneic peripheral blood hematopoietic stem cell transplantation (allo-PBSCT) in chronic myeloid leukemia (CML) patients conditioned with fludarabine-busulfan (FB) reduced intensity regimen. METHODS: Forty-four patients received FB (Flud 30 mgxm(-2)xd(-1) x 5 d, BU 4 mgxkg(-1)xd( 1) x 3 d) conditioning followed by allo-PBSCT. Of them, 29 patients were transplanted with related donor and 15 unrelated donor (URD). All patients received mycophenolate mofetil (MMF), CsA and MTX for acute GVHD (aGVHD) prophylaxis. 5 mg/kg rabbit-antithymocyte globulin (ATG-Fresenius) was incorporated in 15 URD recipients. RESULTS: All patients were successfully engrafted. The median times to ANC above 0.5 x 10(9)/L in related (RG) and unrelated groups (URG) were 13.7 (9 - 18) d and 13.6 (12 - 17) d, and PLT above 20 x 10(9)/L were 15.3 (9 - 20) d and 14.7 (10 - 26) d, respectively. Two patients in RG. 1 in URG developed graft rejection 5 - 8 months after transplantation. One of the two patients in RG received second transplantation and engrafted. The cumulative incidence of aGVHD and cGVHD were 13.8% (4/29) and 46.4% (13/28) in RG, and were 33.3% (5/15) and 57.1% (8/14) in URG respectively. Two patients in RG relapsed after transplantation, and obtained CR again after donor stem cell infusion (DSI). Median time of follow-up was 34.7 (2 - 73) months. Thirty-four patients were alive and 10 died. The main causes of death were IP, GVHD, graft rejection and infection. The 5-year overall survival (OS) probability was 77.0%, and the disease-free-survival (DFS) was 73.9%, of which, 79.0% and 74.1% were in RG, and 73.3% and 73.3% in URG, respectively. CONCLUSIONS: Fludarabine-busulfan based reduced intensity conditioning for allo PBSCT with either related or unrelated donors is a safe, less toxic and curative approach to CML. PMID- 20302793 TI - [Establishment of murine allogeneic umbilical cord blood cell transplantation model and study on the mechanism of keratinocyte growth factor enhancing immune reconstitution after transplantation.]. AB - OBJECTIVE: To explore the impact and mechanism of keratinocyte growth factor (KGF) on immune reconstitution post murine allogeneic umbilical cord blood transplantation (UCBT). METHODS: Perpheral blood (PB) from 19.5-day embryos post conception (E 19.5 d) mice was used as umbilical cord blood (UCB) graft. Thirty two BALB/c mice were randomly assigned to 4 groups with 8 mice each in the first cohort UCBT. Mice were infused with PBS (control group) or 1 x 10(6) (group 1A), 2 x 10(6) (group 1B), 3 x 10(6) UCB mononuclear cells (MNCs) (group 1C), respectively. Twenty-four BALB/c mice were randomly assigned to 3 groups with 8 mice each in the second cohort UCBT. Mice were injected with 1 x 10(6) (group 2A), 2 x 10(6) (group 1B) or 3 x 10(6) (UCB) MNCs (group 2C). All mice received platelet transfusion on +8d. Sixteen BALB/c mice were randomly assigned to 2 groups with 8 mice each in the third cohort UCBT. Mice were injected s.c. with KGF (group 3) or PBS (control group) before TBI. All mice were injected with 2 x 10(6) UCB MNCs and were supported with platelet transfusion on +8 d. The survival time, splenic lymphoid cell subsets, sjTREC assay were observed after UCBT. RESULTS: The 100-day survival of mice were 2, 3 and 3 in group 1A, 1B, 1C and 7, 8, 8 in group 2A, 2B, 2C, respectively. The splenic T, NKT, NK and B cell counts on +35 d were (9.57 +/- 0.74) x 10(6), (0.64 +/- 0.06) x 10(6), (1.43 +/- 0.10) x 10(6) and (19.13 +/- 1.50) x 10(6) in control group, respectively; while were (13.47 +/- 0.74) x 10(6), (0.89 +/- 0.03) x 10(6), (1.79 +/- 0.04) x 10(6) and (20.50 +/- 0.91) x 10(6) in group 3, respectively, being significantly higher than in control group. The sjTREC level was 182.2 +/- 10.7copies per 10(5) cells in control group; while was 224.2 +/- 9.6 copied per 10(5) cells in group 3, being significantly higher than in control group (P = 0.019). CONCLUSIONS: Peripheral blood from E19.5d is rich in hematopoietic stem cells. A murine allogeneic UCBT model with platelet support on +8 d is established. KGF treatment can enhance thymic output and improve T cell immune reconstitution after UCBT. PMID- 20302794 TI - [Effects of HMGB1 on human cord blood CD34(+) hematopoietic stem cells proliferation and differentiation in vitro.]. AB - OBJECTIVE: To study both the release of HMGB1 from irradiation-treated mesenchymal stem cells (MSCs) and the effects of HMGB1 on human cord blood CD34(+) hematopoietic progenitor cell proliferation and differentiation. METHODS: MSCs were obtained from human bone marrow. HMGB1 released by the MSCs after treatment with 12 Gy gamma-ray irradiation was determined by enzyme linked immunosorbent assay (ELISA). CD34(+) cells were positively selected with a MACS CD34 isolation kit. The freshly isolated CD34(+) cells were cultured in the presence of HMGB1 for 6 days. Phenotype of cultured cells surface molecules (CD13, CD14, CD11c, CD41 and CD71) were analyzed by flow cytometry. The proliferation and differentiation capacities of cord blood HSCs were assayed by colony forming cell assay. The receptors of HMGB1 (RAGE, TLR2 and TLR4) on cord blood CD34(+) cells were detected by flow cytometry. RESULTS: HMGB1 level in the supernatant ?[(4.3 +/- 0.9) ng/ml?] of the irradiated MSC was significantly higher than that in control ?[(0.4 +/- 0.2) ng/ml?] (P < 0.01). Human cord blood CD34(+) cells expressed the HMGB1 receptors RAGE, TLR2 and TLR4. The HMGB1 treated CD34(+) cells contained higher proportions of CD13(+) ?[(32.6 +/- 5.9)% vs (18.4 +/- 3.8)%?], CD14(+)?[(25.4 +/- 4.4)% vs (12.6 +/- 2.7)%?], CD11c(+) ?[(20.3 +/- 3.9)% vs (9.8 +/- 2.1)%?], CD71(+) ?[(47.1 +/- 7.4)% vs (26.6 +/- 4.6)%?] cells compared with control group did. But HMGB1 did not induce the generation of CD41(+) cells ?[(1.3 +/- 0.5)% vs (1.1 +/- 0.4)%?]. Furthermore, HMGB1 profoundly induced the growth of BFU-E, CFU-GM and total CFU in a dose dependent manner, and this effect was partially inhibited by TLR2 and TLR4 antibodies. CONCLUSION: Human MSC treated with gamma-ray irradiation can release HMGB1, which can induce the proliferation and differentiation of human cord CD34(+) cells. PMID- 20302795 TI - [A novel single nucleotide polymorphism-based method for quantitative assessment of chimerism after allogeneic stem cell transplantation.]. AB - OBJECTIVE: To develop a novel single nucleotide polymorphism (SNP)-PCR based method for quantitative detection of chimerism after allogeneic haemopoietic stem cell transplantation (allo-HSCT), and to explore its feasibility, accuracy and superiority. METHODS: 18 SNP loci were sereened to identify informative markers for detecting chimerism in each donor/recipient pair before transplantation. Then the chimerism rate of each informative marker was analyzed by real-time quantitative PCR (RQ-PCR). The accuracy and sensitivity were verified by multiple proportion dilution and analogy chimerism compared with quantitative detection of short tandem repeat (STR)-PCR, fluorescence in situ hybridization (FISH) and fusion gene. RESULTS: (1) The average slope of the 17 time amplications of the internal control plasmid was -3.39, the average intercept was 39.97, correlation coefficients were more than 0.995, which was close to the theoretical level. The intra- and interassay variability was 0.50% and 1.1%, respectively, which were both in the allowed ranges. A linear correlation with artificial mixed chimerism is above 0.99 and a sensitivity of 0.01% proved reproducible. (2) At least one informative marker could be found in over 95% of 40 donor/recipient pairs. The results of the chimerisms derived from SNP-PCR were consistent with that from STR PCR (96.7%), FISH and fusion gene analasis (P > 0.05); the quantitative results of special fusion gene transcripts were negtive in complete chimerism samples, and positive in mixed chimerism samples. CONCLUSIONS: This new assay which overcome the PCR competition and plateau biases of STR-PCR provides an accurate, reliable and rapid quantitative assessment of mixed chimerism after allo transplantation. It is highly promising for of clinical application and may take the place of STR-PCR in the conventional chimerisim assessment. PMID- 20302796 TI - [Evaluation of polymorphic post-allotransplant lymphoproliferative disorder by flow cytometry.]. AB - OBJECTIVE: To study the role of flow cytometry (FCM) in detection of polymorphic post-transplant lymphoproliferative disorders (PTLD). METHODS AND RESULTS: Two patients presented with fever and multiple lymphadenopathy on day 46 and day 50 respectively after successful allogeneic hematopoietic stem cell transplantation (allo-HSCT). The symptoms couldn't be controlled by antibiotics. The polymorphic PTLD was diagnosed based on the elevation of bone marrow EB virus DNA and detection of subsets of light chain restricted B cells and/or plasma cells in peripheral blood (PB) samples. The lymphocyte immunophenotypes from PB and/or bone marrow (BM) samples were serially tested by FCM after lowering the dose of immunosupressive agents and treating with antivirus drugs, anti-CD20 antibodies, and cytotoxic T cell infusion. B cells were undetable in two patient, but monoclonal plasma cells appeared or maintained. One patient died after two weeks. Another patient was still on treatment. B cells and plasms cells couldn't be detected in her PB, but there were monoclonal plasma cells in her BM. FCM have a prominent advantage in detect polymorphic PTLD, since it can effectively recognize different cell groups in blood and identify monoclonal subsets. Besides, the immunophenotype of plasma cells in polymorphic PTLD might be different from that in typical plasma cell myeloma. CONCLUSION: Polymorphic PTLD can be detected and followed up by FCM. BM is more suitable than PB for monitoing the disease. Besides lymph node biopsy, B cell abnormaliity could be detected in PB in allo-HSCT patients. PMID- 20302797 TI - [Distribution of WHO subtypes, initial treatment outcomes and prognosis study of 623 unselected adult patients with acute myeloid leukaemia in Shanghai.]. AB - OBJECTIVE: To investigate the current status of acute myeloid leukemia (AML) treatment in Shanghai. METHODS: From 2003 to 2007, a total of successive 623 patients with adult AML were diagnosed and classified according to WHO criteria. Survival rate or median survival was analysed by Kaplan-Meier curve and COX regression model and to compare the differences in treatment effectiveness with those reported in developed countries and in Shanghai from 1984 to 1994. RESULTS: Total CR rate was 66.5%, median survival time was 18 months and estimated survival at 3 year was 30.8%. The 3-year relapse rate was 55.1%. The CR rate was similar to that in developed countries, but long-term survival was worse. The CR rate and survival were increased markedly compared with data collected from 1984 to 1994 in Shanghai. Induction regimens based on idarubicin, daunorubicin or homoharringtonine had similar CR rates and survivals. Karyotype was the most important prognostic factor. The CR rate was 87.3% (68/79), 61.8% (189/306) and 42.9% (48/112) in favorable (excluding APL), intermediate and adverse cytogenetic risk groups, respectively. The CR rate of APL was 91.3%. Multilineage dysplasia in de novo AML was not an independent prognostic factor after adjusted by cytogenetics, age and WBC count. Poor karyotype, old age and high WBC count were the most important prognostic factors. CONCLUSIONS: The CR rate and survival of AML were improved in the past 20 years. The short-term treatment outcome of AML was comparable to that in developed countries, while the long-term one was worse. Improvement in the long-term treatment outcome in China is an important challenge. PMID- 20302799 TI - [In Process Citation]. PMID- 20302798 TI - [The role of marrow derived mesenchymal stem cells in the prevention and treatment of acute graft-versus-host in mice.]. AB - OBJECTIVE: To observe the prevention and treatment of acute graft-versus-host disease (aGVHD) by murine marrow mesenchymal stem cells (MSCs) in vivo. METHODS: Allogeneic aGVHD model was established with lethally irradiated BALB/c recipients receiving allogeneic BM (BMC) and spleen cells (SP) from C57BL/6 with or without mMSCs at different dose and different time posttransplantation. Six groups were set up, group 1 (irradiation control group); group 2 (i.v. BMC only); group 3 (i.v. SP+ BMC); group 4 (i.v. SP + BMC + 1 x 10(5) mMSC at day 0); group 5 (i.v. SP + BMC +5 x 10(5) mMSC at day 0); group 6 (i.v. SP + BMC +1 x 10(5) mMSC at day 7). The survival was monitored daily. mMSCs infected with adenoviral vector (Ad GFP) were injected into aGVHD model to observe the distribution of MSCs in vivo. RESULTS: (1) Addition of donor mMSCs significantly controlled the lethal GVHD. The survival time (day) in group 1 was 13.5 +/- 2.6, group 3 11.1 +/- 4.0, group 4 26.4 +/- 7.7, group 5 22.7 +/- 9.2, group 6 22.9 +/- 8.2, respectively. The difference between groups 4-6 and group 3 was statistically significant (P < 0.01), but there was no difference among groups 4-6 (P = 0.28); There was less lymphocyte infiltration and architectural disruption in the intestine and spleen of groups 4-6 than that of group 3; (2) mMSCs significantly reduced IFN-gamma and TNF-alpha in the serum of recipient mouse; the levels of IFN-gamma in groups 3, 4, 5, 6 were (607.9 +/- 157.1), (143.6 +/- 37.5), (117.0 +/- 77.8), (131.4 +/- 63.4) ng/L, respectively. And of TNF-alpha were (52.31 +/- 17.95), (6.02 +/- 3.99), (5.21 +/- 0.28), (22.39 +/- 18.21) ng/L, respectively. mMSCs had no effect on allogeneic T cell proliferation in GVHD model but increased apoptosis of allogeneic T cells. The percentage of CD3(+) Annexin V(+)PI(-) in each group were (10.3 +/- 6.6)%, (13.5 +/- 13.8)%, (19.7 +/- 6.0)%, (16.6 +/- 7.3)%, respectively. (3) After intravenous infusion, large numbers of GFP-MSCs lodged in lungs and intestines while small numbers in the liver, spleen and kidney. CONCLUSIONS: MSCs has no effect on proliferation but induce apoptosis of allo reactive T cells; MSCs can inhibit the second activation of allogeneic T cells, significantly reduce the secretion of IFN-gamma and TNF-alpha; MSCs might be able to repair GVHD target tissues by extensive distribution to lungs, intestines, and liver of the animals. PMID- 20302800 TI - [In Process Citation]. PMID- 20302801 TI - [In Process Citation]. PMID- 20302803 TI - [In Process Citation]. PMID- 20302802 TI - [In Process Citation]. PMID- 20302804 TI - [In Process Citation]. PMID- 20302805 TI - [In Process Citation]. PMID- 20302807 TI - [In Process Citation]. PMID- 20302806 TI - [In Process Citation]. PMID- 20302809 TI - [In Process Citation]. PMID- 20302808 TI - [In Process Citation]. PMID- 20302810 TI - [In Process Citation]. PMID- 20302811 TI - North of England and Scotland Study of Tonsillectomy and Adeno-tonsillectomy in Children(NESSTAC): a pragmatic randomised controlled trial with a parallel non randomised preference study. AB - OBJECTIVES: To examine the clinical effectiveness and cost-effectiveness of tonsillectomy/adeno-tonsillectomy in children aged 4-15 years with recurrent sore throats in comparison with standard non-surgical management. DESIGN: A pragmatic randomised controlled trial with economic analysis comparing surgical intervention with conventional medical treatment in children with recurrent sore throats (trial) and a parallel non-randomised cohort study (cohort study). SETTING: Five secondary care otolaryngology departments located in the north of England or west of Scotland. PARTICIPANTS: 268 (trial: 131 allocated to surgical management; 137 allocated to medical management) and 461 (cohort study: 387 elected to have surgical management; 74 elected to have medical management) children aged between 4 and 15 years on their last birthday with recurrent sore throats. Participants were stratified by age (4-7 years, 8-11 years, 12-15 years). INTERVENTIONS: Treatment was tonsillectomy and adeno-tonsillectomy with adenoid curettage and tonsillectomy by dissection or bipolar diathermy according to surgical preference within 12 weeks of randomisation. The control was non surgical conventional medical treatment only. MAIN OUTCOME MEASURES: The primary clinical outcome was the reported number of episodes of sore throat in the 2 years after entry into the study. Secondary clinical outcomes included: the reported number of episodes of sore throat; number of sore throat-related GP consultations; reported number of symptom-free days; reported severity of sore throats; and surgical and anaesthetic morbidity. In addition to the measurement of these clinical outcomes, the impact of the treatment on costs and quality of life was assessed. RESULTS: Of the 1546 children assessed for eligibility, 817 were excluded (531 not meeting inclusion criteria, 286 refused) and 729 enrolled to the trial (268) or cohort study (461). The mean (standard deviation) episode of sore throats per month was in year 1 - cohort medical 0.59 (0.44), cohort surgical 0.71 (0.50), trial medical 0.64 (0.49), trial surgical 0.50 (0.43); and in year 2 - cohort medical 0.38 (0.34), cohort surgical 0.19 (0.36), trial medical 0.33 (0.43), trial surgical 0.13 (0.21). During both years of follow-up, children randomised to surgical management were less likely to record episodes of sore throat than those randomised to medical management; the incidence rate ratios in years 1 and 2 were 0.70 [95% confidence interval (CI) 0.61 to 0.80] and 0.54 (95% CI 0.42 to 0.70) respectively. The incremental cost-effectiveness ratio was estimated as 261 pounds per sore throat avoided (95% confidence interval 161 pounds to 586 pounds). Parents were willing to pay for the successful treatment of their child's recurrent sore throat (mean 8059 pounds). The estimated incremental cost per quality-adjusted life-year (QALY) ranged from 3129 pounds to 6904 pounds per QALY gained. CONCLUSIONS: Children and parents exhibited strong preferences for the surgical management of recurrent sore throats. The health of all children with recurrent sore throat improves over time, but trial participants randomised to surgical management tended to experience better outcomes than those randomised to medical management. The limitations of the study due to poor response at follow-up support the continuing careful use of 'watchful waiting' and medical management in both primary and secondary care in line with current clinical guidelines until clear-cut evidence of clinical effectiveness and cost-effectiveness is available. TRIAL REGISTRATION: Current Controlled Trials ISRCTN47891548. PMID- 20302812 TI - Genetic animal models for schizophrenia: advantages and limitations of genetic manipulation in drosophila, zebrafish, rodents, and primates. AB - Schizophrenia is a debilitating mental illness in which major initial risks of the disease during neurodevelopment may disturb postnatal brain maturation, which results in onset after puberty. Family, twin, and adoption studies have suggested an important role for genetic factors in the etiology of schizophrenia. To address the etiology-associated mechanisms and disease course, use of genetic models, that is, manipulation of genetic susceptibility factors, is currently considered to be a powerful tool for biological studies. In this manuscript, advantages and possible limitations in manipulating genetic susceptibility factors for schizophrenia toward modeling the disease are discussed. In addition to mouse models, the potential to use drosophila, zebrafish, and primates is underscored. PMID- 20302813 TI - Animal models for schizophrenia via in utero gene transfer: understanding roles for genetic susceptibility factors in brain development. AB - Genetic disturbances of brain development may underlie the pathophysiology of schizophrenia. Recent advances in molecular neurobiology suggest that some genetic risk factors for schizophrenia have multiple roles in various brain regions depending on the developmental stage. Furthermore, these factors are likely to act synergistically or epistatically in common molecular pathways, possibly contributing to disease pathology. Thus, a technique that can manipulate the expression of more than one gene simultaneously in animal models is necessary to address such molecular pathways. To produce such animal models, in utero gene transfer technique is one useful method. Given that plasmid-based cell-type specific and inducible gene expression systems are now available, combining these technologies and in utero gene transfer opens a new window to examine the functional role of genetic risk factors for schizophrenia by conducting multiple gene targeting in a spatial and temporal manner. The utility of animal models produced by in utero gene transfer will also be expected to be evaluated in terms of functional and behavioral outcomes after puberty, which may be associated with schizophrenia pathology. PMID- 20302814 TI - Gene manipulation with stereotaxic viral infection for psychiatric research: spatiotemporal components for schizophrenia. AB - Schizophrenia (SZ) is a highly polygenic disease with strong genetic predisposition. Although genetic susceptibility factors for SZ are likely to have an influence in some brain regions and related neural circuits during neurodevelopment, direct proof for spatiotemporal causality in the development of SZ, and the alteration of what gene function at what brain region during what developmental stage, remains to be elucidated. Gene manipulation by viral vector stereotaxically injected into a specific brain region is now becoming available for psychiatric research. This technique has several advantages, e.g., the exceptional spatiotemporal control, simultaneous manipulation of multiple genes, and its simple protocol. These properties can make this technique one of the most valuable approaches for research in SZ, which is a complex brain disorder with multifactorial, genetic, and developmental features. This review summarizes the benefits and actual use of this technique together with discussion of spatiotemporal aspect for SZ. PMID- 20302815 TI - ENU-induced mutant mice for a next-generation gene-targeting system. AB - By the N-ethyl-N-nitrosourea (ENU)-based gene-driven mutagenesis, it is now possible to obtain allelic series of mutant mouse strains, each of which carries a different base substitution in any target gene. This new reverse genetic tool has become available based on the ENU mutant mouse library. The ENU mutant mouse library consists of dual archives of frozen sperm and corresponding genomic DNA derived from Generation-1 (G1) male mice, each of which carries thousands of ENU induced base substitutions. Firstly, ENU-induced mutations in the target gene are screened from the genomic DNA archive by using one of the high-throughput mutation discovery systems. The identified mutations are then revived as live mice by the in vitro fertilization (IVF) and embryo transfer (ET) technology. Just like the knockout (KO) mouse system, the revived mutant strains are finally subjected to the three-generation scheme to reveal the gene function(s) of the target gene. This new reverse genetics or "next-generation gene-targeting system" allows us to elucidate the biological roles of the mouse genome in terms of single base-pair effects not only for the protein-coding sequences but also for any genomic sequences. PMID- 20302816 TI - Inducible and conditional transgenic mouse models of schizophrenia. AB - Schizophrenia is a devastating disorder. Despite the advance in research techniques in the last couple of decades, the pathogenesis of the disorder still remains poorly understood. Given the lack of pathognomonic feature of the disease and difficulty to analyze molecular pathways in patients, animal models have been instrumental in advancing our understanding of the disease. Recent progress in genetics has identified candidate susceptibility genes for schizophrenia, and generation of new genetic animal models has begun to provide valuable insights into the disease development. However, the complex neurodevelopmental and heterogeneous nature of schizophrenia still poses tremendous challenges for creating credible mouse models. In this review, we will discuss how current genetic systems of temporal and conditional regulation of gene expression have shed lights on the functions of the candidate genes in mouse models of schizophrenia. We also consider the strength and weaknesses of each model. We will argue that further development of more sophisticated genetic animal models is crucial for clarifying the unknowns of schizophrenia. PMID- 20302817 TI - NR1 knockdown mice as a representative model of the glutamate hypothesis of schizophrenia. AB - N-methyl d-aspartate (NMDA) receptor subunit NR1 knockdown (NR1-KD) mice have a global reduction of NMDA receptors, enabling their use as a genetic model to study the role of NMDA receptors in the pathophysiology of schizophrenia. This targeted mutation results in a spectrum of altered behaviors that are similar to those induced by NMDA receptor antagonists, which have long been used to model schizophrenia in animals. NR1-KD mice serve as a complementary tool to pharmacological models, providing insight into the consequences of sustained NMDA receptor dysfunction in early brain development and throughout the life of the animal. Though in many respects the phenotype of NR1-KD mice mimics that of acute NMDA receptor antagonism, there are also notable differences. In this chapter we highlight some of the molecular, behavioral, and neurophysiological phenotypes of NR1-KD mice and compare these to pharmacological models of NMDA receptor dysfunction. Through the study of these models, our improved understanding of how the brain adapts to persistent NMDA receptor hypofunction may eventually suggest new therapeutic strategies for schizophrenia. PMID- 20302818 TI - Modeling excess striatal D2 receptors in mice. AB - Dopaminergic hyperactivity in the striatum has been one of the most replicated physiological findings in patients with schizophrenia. To study the consequences of increased D2 receptor density in the striatum, as it has been observed in patients with schizophrenia, D2 receptors have been selectively over-expressed in the mouse striatum. Here, the analysis of this mouse model is summarized and discussed in the context of the dopamine hypothesis of schizophrenia. PMID- 20302819 TI - Differential function of phosphodiesterase families in the brain: gaining insights through the use of genetically modified animals. AB - Phosphodiesterases (PDEs) are the only known enzymes to degrade cAMP and cGMP, intracellular signaling molecules key to numerous cellular functions. There are 11 PDE families identified to date, and each is expressed in a unique pattern across brain regions. Here, we review genetic mouse models in which PDEs are either directly manipulated (e.g., genetically deleted) or are changed in a compensatory manner due to the manipulation of another target. We believe these genetic mouse models have contributed to our understanding of how the PDE1, PDE4, and PDE10 families contribute uniquely to overall brain function. PMID- 20302820 TI - Gene models of schizophrenia: DISC1 mouse models. AB - Disrupted in Schizophrenia-1 (DISC1) is one of the most likely susceptibility genes for schizophrenia (SZ). DISC1 is being established as a hub protein with various functions in the pre- and postnatal development of the nervous system. Since generation of a knockout (KO) mouse has proved challenging, various alternative approaches have been taken. Seven DISC1 mouse models have been described to date. All of them display neuroanatomical and behavioral abnormalities relevant to SZ, although most of them have not been fully characterized yet, requiring further analysis. NRG1 and ErbB4, also highly promising susceptibility genes for SZ, share many features with DISC1. They are involved in various aspects of pre- and postnatal neurodevelopment. The NRG1 and ErbB4 mouse models also display neuroanatomical and behavioral abnormalities similar to the DISC1 mouse models. In the future, four main directions need further study. First, further characterization of the seven DISC1 mouse models, especially in light of basic research findings. Second, more extensive employment of the inducible models. Third, generation of a DISC1 KO. Fourth, combination of the DISC1 mouse models with other risk factors: crossing with other genetic models such as NRG1/ErbB4 mutants and exposure to environmental risk factors. PMID- 20302822 TI - Zebrafish: a model system to examine the neurodevelopmental basis of schizophrenia. AB - Schizophrenia is a devastating disorder caused by both genetic and environmental factors that disrupt brain development and function. It is distinguished as a neurodevelopmental disorder in part due to early cognitive impairments, behavioral dysfunction in childhood and adolescence, and abnormalities in central nervous system development. Zebrafish are recognized as an important vertebrate model for human development and disease. There are many advantages of using zebrafish as a model, such as low cost to maintain, rapid life cycle, optical clarity and rapid external embryonic development. Furthermore, multiple molecular genetic techniques have been developed to readily study gene function during development. In this review, we will discuss the advantages of using the zebrafish model system to study schizophrenia. PMID- 20302821 TI - The sandy (sdy) mouse: a dysbindin-1 mutant relevant to schizophrenia research. AB - Dysbindin-1 reductions appear to be common in dysfunctional brain areas of schizophrenia cases. In the absence of a dysbindin-1 knockout, sandy (sdy) mice provide our only means of studying the potential contribution of this protein to clinical features of schizophrenia in live animals. Our knowledge of sandy mice is reviewed here. These mice have a deletion mutation that arose spontaneously in DBA/2J mice in the gene encoding dysbindin-1 (Dtnbp1). This null protein mutation (Dtnbp1(sdy)) leads to an absence of dysbindin-1 in homozygotes, as well as reductions in several direct and indirect binding partners of dysbindin-1 that contribute to the protein assembly known as BLOC-1. Studies of sdy mice on the original DBA/2J background and on a C57BL/6J background indicate that the Dtnbp1(sdy) mutation does not affect viability, basic sensory or motor functions, or measures of anxiety and motivation. Such studies do indicate, however, that the mutation affects several biological functions, including adrenal neurosecretion and pre- and postsynaptic aspects of dopaminergic, glutamatergic, and GABAergic transmission. These effects and those on prepulse inhibition, social interaction, and diverse aspects of spatial memory suggest that homozygous sdy mice may model various features of schizophrenia. PMID- 20302823 TI - Modeling schizophrenia in flies. AB - Schizophrenia is a debilitating mental illness that affects 1% of the population worldwide. Although its molecular etiology remains unclear, recent advances in human psychiatric genetics have identified a large number of candidate genetic risk factors involved in schizophrenia. Modeling the disease in genetically tractable animals is thus a challenging but increasingly important task. In this review, I discuss the potential problems and perspectives associated with modeling schizophrenia in fruit flies, and briefly review the recent studies analyzing the molecular and cellular functions of Disrupted-In-Schizophrenia-1 (DISC1) in transgenic flies. PMID- 20302825 TI - Preface. PMID- 20302824 TI - Primate models of schizophrenia: future possibilities. AB - Schizophrenia is a disorder of the association cortices, with especially prominent structural and functional deficiencies in the dorsolateral prefrontal cortex (PFC). True dorsolateral PFC is found only in higher primates, and is characterized by highly elaborate pyramidal cells with extensive recurrent connections. The development of the primate PFC also involves distinct developmental and genetic pathways. Thus, primate models may be particularly important in determining the functional impact of genetic changes in patients with schizophrenia. Genes involved with pyramidal cell network connectivity may be especially important to study in primates, as their effects may be magnified in the extensively connected primate neurons. Adeno-associated virus technology appears particularly promising for studying the impact of genetic insults on the structure and function of the primate association cortex. PMID- 20302826 TI - Chapter 1 - Drug delivery to the brain using colloidal carriers. AB - Many neurodegenerative diseases, cancer, and infections of the brain become more prevalent as populations become older. Despite major advances in neuroscience, the blood-brain barrier (BBB) ensures that many potential therapeutics cannot reach the central nervous system (CNS). The BBB is formed by the complex tight junctions between the endothelial cells of the brain capillaries and their low endocytic activity. It results in the capillary wall that behaves as a continuous lipid bilayer and prevents the passage of polar substances. Drug delivery to the brain has remained one of the most vexing problems in translational neuroscience research, because of the difficulties posed by the BBB. Several strategies for delivering drugs to the CNS have been developed. This review rationalizes the strategies to target drugs to the brain by using different colloids. PMID- 20302827 TI - Chapter 2 - Quantum dot nanotechnologies for neuroimaging. AB - Functionalized quantum dot nanocrystals provide an opportunity for high signal-to noise ratio specific labeling of cells with micron-scale spatial resolution, and extend the cellular imaging toolbox available to the cellular neurobiologist. In this review we discuss previous work from our group aimed at optimizing quantum dot labeling protocols specific to neurons and neural glial cells, labeling and imaging of intact neural retinal tissue sections in a rat model of retinal degeneration focused on the formation of the glial scar following focal reactive gliosis, and on the characterization and estimation of the number of functionally available antibodies for biological binding conjugated to quantum dots following two popular conjugation schemes. PMID- 20302828 TI - Chapter 3 - Colloidal systems for CNS drug delivery. AB - The pharmaceutical treatment of central nervous system (CNS) disorders is the second largest area of therapy, following cardiovascular diseases. Nowadays, noninvasive drug delivery systems for CNS are actively studied. The development of these new delivery systems started with the discovery that properly surface engineered colloidal vectors, and in particular liposomes and polymeric nanoparticles, with a diameter approximately 200nm, were shown to be able to cross the blood-brain barrier (BBB) without apparent damage, and to deliver drugs or genetic materials into the brain. However, even if this ability was confirmed by confocal microscopy and measured by biodistribution experiments or by means of the pharmacological effect exerted by the embedded drugs, a clear understanding of the main characteristics of the colloidal systems that are important for BBB crossing is still lacking. It is also shown that the presence of the drug is able to modify the surface of these systems, with unpredictable results on the colloidal systems biodistribution; thus, the results obtained in the absence of the loaded drug have to be taken cautiously. Moreover, since the loaded drug is only a fraction of the colloidal system that is administered, the presence of the carrier in the body and into CNS, especially in the case of long-term therapies, might cause adverse effects not yet fully understood. Thus, even if promising results have been obtained, and some colloidal systems loaded with a drug are the US Food and Drug Administration (FDA) approved for human use (but not for brain targeting), a long way of research has to be done in order to use these drug delivery systems for the treatment of CNS pathologies. PMID- 20302829 TI - Chapter 4 - Applications of nanotechnology in molecular imaging of the brain. AB - Rapid advances in the field of nanotechnology promise revolutionary improvements in the diagnosis and therapy of neuroinflammatory disorders. An array of iron oxide nano- and microparticle agents have been developed for in vivo molecular magnetic resonance imaging (mMRI) of cerebrovascular endothelial targets, such as vascular cell adhesion molecule-1 (VCAM-1), E-selectin, and the glycoprotein receptor GP IIb/IIIa expressed on activated platelets. Molecular markers of glioma cells, such as matrix metalloproteinase-2 (MMP-2), and markers for brain tumor angiogenesis, such as alpha (v) beta (3) integrin (alpha(v)beta(3)), have also been successfully targeted using nanoparticle imaging probes. This chapter provides an overview of targeted, iron oxide nano- and microparticles that have been applied for in vivo mMRI of the brain in experimental models of multiple sclerosis (MS), brain ischemia, cerebral malaria (CM), brain cancer, and Alzheimer's disease. The potential of targeted nanoparticle agents for application in clinical imaging is also discussed, including multimodal and therapeutic approaches. PMID- 20302830 TI - Chapter 5 - Development of iron chelator-nanoparticle conjugates as potential therapeutic agents for Alzheimer disease. AB - Oxidative stress is known to play a key role in the initiation and promotion of the neurodegeneration that characterizes the pathogenesis of Alzheimer disease (AD). An accumulation of redox active transition metals, including iron and copper, is likely a major generator of reactive oxidative species and other free radicals and is thought to induce a detrimental cycle of oxidative stress, amyloid-beta aggregation, and neurodegeneration. As such, metal chelators may provide an alternative therapeutic approach to sequester redox active metals and prevent the onslaught of oxidative damage. Unfortunately, however, metal chelation approaches are currently limited in their potential, since many cannot readily pass the blood-brain barrier (BBB), due to their hydrophilicity, and many are neurotoxic at high concentrations. To circumvent such issues, here we describe the development of iron chelator-nanoparticle conjugation that allows delivery of target chelator to the brain in the absence of neurotoxicity. Such nanoparticle delivery of iron chelators will likely provide a highly advantageous mode of attack on the oxidative stress that plagues AD as well as other conditions characterized by excess metal accumulation. PMID- 20302831 TI - Chapter 6 - Carbon nanotubes as substrates/scaffolds for neural cell growth. AB - Carbon nanotubes (CNTs) due to their unique properties have sparked interest for their use in biomedical applications in recent years. In particular, the use of CNTs as substrates/scaffolds for neural cell growth has been an area of active research over the past decade. CNTs, either native or functionalized with various chemical groups, are biocompatible with neuronal cell adhesion and growth. Functionalized CNTs can modulate the neuronal growth in graded manner; positively charged CNTs promoted neurite outgrowth of hippocampal neurons in culture to a greater extent than when these cells were grown on neutral or negatively charged CNTs. Conductivity and mechanical properties of CNTs have been shown to affect neuronal morphology as well. Other neural cells, such as stem and glial cells, can also be successfully grown on CNT substrates. While currently the acute toxicity of CNTs is considered comparable to that of other forms of carbon, the long-term exposures limits need to be established in order to use these materials as neural prosthesis. Nonetheless, accumulating data support the use of CNTs as a biocompatible and permissive substrate/scaffold for neural cells and such application holds great potential in biomedicine. PMID- 20302832 TI - Chapter 7 - Neuromodulation: Deep brain stimulation, sensory neuroprostheses, and the neural-electrical interface. AB - Although neuromodulation with implanted brain electrodes (deep brain stimulation, DBS) has been increasingly effective in treating many patients with movement disorders (e.g., advanced Parkinson's disease) over the past 20 years, the techniques have changed little for more than 50 years. After summarizing the current state of DBS, this chapter considers (1) the advances being offered by computational analysis techniques as well as (2) the benefits of monitoring and modulating brain chemical activity in addition to brain electrical activity. A review of the current state of sensory neuroprostheses follows, with consideration of emerging data on the optimal configuration of micron-sized retinal prostheses as well as on the optimal site for stimulation of cells in the retina. Very recent findings on nanotechniques to enhance charge transfer from prosthesis to cell (neuronal or glial), that is, enhancement of the neural electrical interface, are then reviewed. The final section summarizes areas of potential cross-fertilization between those centers developing sensory neuroprostheses and those centers developing nanotechniques for DBS. PMID- 20302833 TI - Chapter 8 - Nanoparticles: Transport across the olfactory epithelium and application to the assessment of brain function in health and disease. AB - The exciting advances within nanotechnology are beginning to be harnessed by the medical field. Nanoparticles have been used for drug delivery into the brain and have been explored for imaging, sensing, and analytical purposes. The science of nanoparticles encompasses a vast array of biological, chemical, physical, and engineering research, different aspects of which are specifically addressed in each of the chapters of this volume. Nanomaterials such as nanospheres, nanotubes, nanowires, fullerene derivatives (buckyballs), and quantum dots (Qdots) are at the forefront of scientific attention, as they provide new consumer products and advance the scientific development of novel analytical tools in medicine and in the physical sciences. This chapter will briefly survey some aspects of nanoparticle biology focusing on the following: (1) the role of olfactory nanoparticle transport into the central nervous system (CNS), both as a potential route for effective drug delivery and as a route for the passage of noxious substances into the brain proper; (2) nanoparticles as sensors of cell function and toxicity; and (3) some adverse effects of nanoparticles on the dysregulation of brain redox status. PMID- 20302834 TI - Chapter 9 - Nanoparticles influence pathophysiology of spinal cord injury and repair. AB - Spinal cord injury (SCI) is a serious clinical problem for which no suitable therapeutic strategies have been worked out so far. Recent studies suggest that the SCI and its pathophysiological responses could be altered by systemic exposure to nanoparticles. Thus, SCI when made in animals intoxicated with engineered nanoparticles from metals or silica dust worsened the outcome. On the other hand, drugs tagged with titanium (TiO(2)) nanoparticles or encapsulated in liposomes could enhance their neuroprotective efficacy following SCI. Thus, to expand our knowledge on nanoparticle-induced alterations in the spinal cord pathophysiology further research is needed. These investigations will help to develop new strategies to achieve neuroprotection in SCI, for example, using nanodrug delivery. New results from our laboratory showed that nanoparticle induced exacerbation of cord pathology following trauma can be reduced when the suitable drugs tagged with TiO(2) nanowires were administered into the spinal cord as compared to those drugs given alone. This indicates that nanoparticles depending on the exposure and its usage could induce both neurotoxicity and neuroprotection. This review discusses the potential adverse or therapeutic utilities of nanoparticles in SCI largely based on our own investigations. In addition, possible mechanisms of nanoparticle-induced exacerbation of cord pathology or enhanced neuroprotection following nanodrug delivery is described in light of recently available data in this rapidly emerging field of nanoneurosciences. PMID- 20302835 TI - Chapter 10 - Solid lipid nanoparticles and microemulsions for drug delivery The CNS. AB - The chapter examined solid lipid nanoparticles (SLN) and microemulsions, chosen as carriers of drugs, administered in vivo to be transported to the central nervous system. Drugs of different structures and for different therapies have been studied such as doxorubicin SLN stealth and nonstealth administered in rats by intravenous route, apomorphine SLN administered in rats by duodenal route, melatonin SLN administered by transdermal and oral routes in humans, and apomorphine microemulsion administered by transdermal route in Parkinson's patients. The pharmacokinetics of the drug, followed in most studies, put in evidence that the many important pharmacokinetic parameters were notably improved versus the drug alone or in a commercial formulation. PMID- 20302836 TI - Chapter 11 - Solid lipid nanoparticles for brain tumors therapy: State of the art and novel challenges. AB - Malignant gliomas, despite aggressive multimodal therapies and adequate supportive care, still maintain poor prognosis. Solid lipid nanoparticles (SLN) are colloidal carriers that could be regarded as a highly flexible platform for brain tumor imaging and therapeutical purposes. In this chapter we will first describe brain tumors characteristics and conventional therapeutical approaches. In the subsequent sections, we will analyze SLN properties, effectiveness, and future perspectives in both imaging and targeted treatment of malignant gliomas. PMID- 20302838 TI - Trinucleotide repeat system for sequence specificity analysis of RNA structure probing reagents. AB - Chemical and enzymatic structural probes have been used for decades to obtain rapid and comprehensive information regarding the molecular architecture of various RNAs. Despite their widespread use, the sequence specificity of these RNA structural probing reagents has not yet been thoroughly characterized. In this study, we revisited the properties of commonly used structural probes such as Pb(II) ions, ribonuclease V1, ribonuclease T2, and the S1 and mung bean nucleases by testing them on highly regular triplet repeat sequences representing phosphodiester bonds with every possible combination of 3' and 5' adjacent nucleotides. We show that Pb(II) ions preferentially cleave after pyrimidines and that S1 nuclease possesses a previously overlooked specificity toward phosphodiester bonds following G residues. We also observed that mung bean nuclease shows a preference for cleaving ApN bonds and that RNase V1 mainly recognizes U residues in both single- and double-stranded RNAs. These data are important for accurate interpretation of the results of structure probing experiments and for assignment of the correct structure to individual RNA molecules. The triplet repeat transcript system described here may be considered as a reliable platform for determining the sequence specificity of other reagents used to probe RNA structure. PMID- 20302837 TI - Chapter 12- Brain as an HIV sequestered site: Use of nanoparticles as a therapeutic option. AB - Patients infected with human immunodeficiency virus (HIV) are at increased risk to develop neurocognitive problems. HIV crosses the blood-brain barrier (BBB) through a variety of means. Once within the brain tissue, HIV stimulates immunoactivation and inflammation that lead to neuronal loss. This review discusses the pathophysiology of HIV within the brain and the treatment modalities used to prevent neurocognitive problems from developing. Modalities that prevent antiretroviral drugs from crossing into the central nervous system and reducing viral load are also discussed. Finally, since drug penetration across the BBB is reduced, the use of nanoparticles as a treatment modality to increase BBB penetration may be an option worth further exploration. PMID- 20302839 TI - Fluorescence anisotropy assay for pharmacological characterization of ligand binding dynamics to melanocortin 4 receptors. AB - Fluorescence anisotropy assay was implemented for characterization of ligand binding dynamics to melanocortin 4 (MC(4)) receptors. This approach enables on line monitoring of reactions that is essential for estimation of more correct binding parameters, understanding of ligand binding and its regulation mechanisms, and design of new drugs with desirable properties. Two different red shifted fluorophore-labeled peptide ligands, Cy3B-NDP-alpha-MSH and TAMRA-NDP alpha-MSH, were used and compared in assays that monitored their binding to MC(4) receptors in membranes of Sf9 insect cells. The Cy3B dye-labeled ligand exhibited improved performance in assays when compared with the TAMRA-labeled ligand, having higher photostability, insensitivity to buffer properties, and better signal/noise ratio. The binding of both ligands to membranes of Sf9 cells expressing MC(4) receptors was saturable and with high affinity. All studied MC(4) receptor-specific nonlabeled ligands displaced fluoroligands' binding in a concentration-dependent manner with potencies in agreement with their pharmacological activities. On-line monitoring of the reactions revealed that equilibrium of peptide binding was not reached even after 3h. Real-time monitoring of ligand binding dynamics enabled us to find optimal experimental conditions for each particular ligand and an improved estimate of their binding parameters. PMID- 20302840 TI - Lipid clustering by three homologous arginine-rich antimicrobial peptides is insensitive to amino acid arrangement and induced secondary structure. AB - Three Arg-rich nonapeptides, containing the same amino acid composition but different sequences, PFWRIRIRR-amide (PR-9), RRPFWIIRR-amide (RR-9) and PRFRWRIRI amide (PI-9), are able to induce segregation of anionic lipids from zwitterionic lipids, as shown by changes in the phase transition properties of lipid mixtures detected by differential scanning calorimetry and freeze fracture electron microscopy. The relative Minimal Inhibitory Concentration (MIC) of these three peptides against several strains of Gram positive bacteria correlated well with the extent to which the lipid composition of the bacterial membrane facilitated peptide-induced clustering of anionic lipids. The lower activity of these three peptides against Gram negative bacteria could be explained by the retention of these peptides in the LPS layer. The membrane morphologies produced by PR-9 as well as by a cathelicidin fragment, KR-12 that had previously been shown to induce anionic lipid clustering, was directly visualized using freeze fracture electron microscopy. This work shows the insensitivity of phase segregation to the specific arrangement of the cationic charges in the peptide sequence as well as to their tendency to form different secondary structures. It also establishes the role of anionic lipid clustering in the presence of zwitterionic lipids in determining antimicrobial selectivity. PMID- 20302841 TI - GUV preparation and imaging: minimizing artifacts. AB - The components of biological membranes are present in a physical mixture. The nonrandom ways that the molecules of lipids and proteins mix together can strongly influence the association of proteins with each other, and the chemical reactions that occur in the membrane, or that are mediated by the membrane. A particular type of nonrandom mixing is the separation of compositionally distinct phases. Any such phase separation would result in preferential partition of some proteins and lipids between the coexisting phases, and thus would influence which proteins could be in contact, and whether a protein could find its target. Phase separation in a plasma membrane would also influence the binding of molecules from outside the cell to the membrane, including recognition proteins on viruses, bacteria, and other cells. The concept of these and other events associated with membrane phase separation are sometimes grouped together as the "raft model" of biological membranes. Several types of experiments are aimed at detecting and characterizing membrane phase separation. Visualizing phase separation has special value, both because the immiscibility is so decisively determined, and also because the type of phase can often be identified. The fluorescence microscope has proven uniquely useful for yielding images of separated phases, both in certain cell preparations, and especially in models of cell membranes. Here we discuss ways to prepare useful model membranes for image studies, and how to avoid some of the artifacts that can plague these studies. PMID- 20302842 TI - Crystal structure and functional insight of HP0420-homolog from Helicobacter felis. AB - Helicobacter pylori infect more than half of the world's population and are considered a cause of peptic ulcer disease and gastric cancer. Recently, hypothetical gene HP0421 was identified in H. pylori as a cholesterol alpha glucosyltransferase, which is required to synthesize cholesteryl glucosides, essential cell wall components of the bacteria. In the same gene-cluster, HP0420 was co-identified, whose function remains unknown. Here we report the crystal structure of HP0420-homolog of H. felis (HF0420) to gain insight into the function of HP0420. The crystal structure, combined with size-exclusion chromatography, reveals that HF0420 adopts a homodimeric hot-dog fold. The crystal structure suggests that HF0420 has enzymatic activity that involves a conserved histidine residue at the end of the central alpha-helix. Subsequent biochemical studies provide clues to the function of HP0420 and HF0420. PMID- 20302843 TI - The role of oxidized low-density lipoprotein in breaking peripheral Th17/Treg balance in patients with acute coronary syndrome. AB - Oxidized low-density lipoprotein (ox-LDL) is an instrumental factor in atherogenesis, however, the effects of ox-LDL on the balance of Th17/Treg in acute coronary syndrome [ACS, including unstable angina (UA) and acute myocardial infarction (AMI)] is still unclear. CD4(+)CD25(+) regulatory T (Treg) cells and Th17 cells, subsets of T-helper cells, play important roles in peripheral immunity and their imbalance leads to the development of tissue inflammation and autoimmune diseases. However, few studies have explored the effect of Th17/Treg balance in plaque destabilization and the onset of ACS. To explore the shift of Th17/Treg balance in ACS patients and the effect of ox-LDL on the balance, we examined the frequencies of Th17 and Treg cells, key transcription factors and relevant cytokines in patients with AMI, UA, stable angina (SA) and controls. We analysed the correlations of serum ox-LDL to Th17/Treg frequency, and the effects of ox-LDL on Th17/Treg cells in vitro. Our study demonstrated that ACS patients have shown a significant increase of Th17 frequency, RORgammat expression and serum Interleukin 17 (IL-17), and a obvious decline of Treg frequency, Foxp3 expression, suppressive function, and serum IL-10. Serum ox-LDL positively correlated with the frequency of Th17 cells and negatively correlated with the frequency of Treg cells. In vitro incubation of peripheral blood mononuclear cells from controls with ox-LDL resulted in a significant reduction of Treg cells and a significant elevation of Th17 cells in a dose- and time-dependant manner. Treg and Th17 cells from ACS patients were significantly more susceptible to ox LDL-mediated alterations. Th17/Treg numerical and functional imbalance exists in ACS patients, and ox-LDL has a direct effect on Th17/Treg imbalance which may contribute to the occurrence of ACS. PMID- 20302844 TI - Flow cytometric analysis of the contributing factors for antimicrobial activity enhancement of cell-penetrating type peptides: case study on engineered apidaecins. AB - Contributing factors for the antimicrobial activity enhancement of N-terminally engineered mutants of cell-penetrating apidaecins were analyzed based on their cell-penetration efficiency. The flow cytometric analysis of the engineered apidaecins labeled with carboxyfluorescein (FAM) revealed their enhanced cell penetrating efficiencies into Escherichia coli that should be one of key factors causing the enhanced antimicrobial activity. It is noteworthy that, for one mutant, the enhancement in antimicrobial activity (18-fold higher than wild type) was greater than that of cell penetration (5.9-fold), suggesting that the N terminal mutation may reinforce both interaction with unidentified intracellular target(s) and cell-penetration efficiency. PMID- 20302845 TI - Isolated tumor endothelial cells maintain specific character during long-term culture. AB - Tumor angiogenesis is necessary for solid tumor progression and metastasis. Increasing evidence indicates that tumor endothelial cells (TECs) are more relevant to the study of tumor angiogenesis than normal endothelial cells (NECs) because their morphologies and gene expression are different from NECs. However, it is challenging to isolate and culture large numbers of pure ECs from tumor tissue since the percentage of ECs is only about 1-2% and tumor cells and fibroblasts easily overgrow them. In addition, there has been concern that isolated TECs may lose their special phenotype once they are dissociated from tumor cells. In this study, we have successfully purified murine TECs from four different human tumor xenografts and NECs from murine dermal tissue. Isolated ECs expressed endothelial markers, such as CD31, VE-cadherin (CD144), and endoglin (CD105), for more than 3 months after isolation. TECs maintained tumor endothelial-specific markers, such as tumor endothelial marker 8 (TEM8) and aminopeptidase N (APN), as in tumor blood vessels in vivo. In addition, TECs were more proliferative and motile than NECs. TECs showed a higher response to VEGF and higher expression of VEGF receptors-1 and -2 than NECs did. Stem cell antigen 1 was up-regulated in all four TECs, suggesting that they have a kind of stemness. Cultured TECs maintain distinct biological differences from NECs as in vivo. In conclusion, it was suggested that TECs are relevant material for tumor angiogenesis research. PMID- 20302846 TI - Development of small-molecule inhibitors of the group I p21-activated kinases, emerging therapeutic targets in cancer. AB - The p21-activated kinases (PAKs), immediate downstream effectors of the small G proteins of the Rac/cdc42 family, are critical mediators of signaling pathways regulating cellular behaviors and as such, have been implicated in pathological conditions including cancer. Recent studies have validated the requirement for PAKs in promoting tumorigenesis in breast carcinoma and neurofibromatosis. Thus, there has been considerable interest in the development of inhibitors to the PAKs, as biological markers and leads for the development of therapeutics. While initial approaches were based on screening for competitive organic inhibitors, more recent efforts have focused on the identification of allosteric inhibitors, organometallic ATP-competitive inhibitors and the use of PAK1/inhibitor crystal structures for inhibitor optimization. This has led to the identification of highly selective and potent inhibitors, which will serve as a basis for further development of inhibitors for therapeutic applications. PMID- 20302847 TI - HMBA depolymerizes microtubules, activates mitotic checkpoints and induces mitotic block in MCF-7 cells by binding at the colchicine site in tubulin. AB - 10-[(3-Hydroxy-4-methoxybenzylidene)]-9(10H)-anthracenone (HMBA), a synthetic compound, has been reported to have a potent antitumor activity. In this study, we found that HMBA depolymerized microtubules in MCF-7 cells and produced aberrant spindles in the MCF-7 cells. It also reduced the distance between the centrosomes and activated the mitotic checkpoint proteins BubR1 and Mad2. Further, HMBA inhibited the progression of MCF-7 cells in mitosis and induced apoptotic cell death involving p53 pathway. In vitro, HMBA bound to purified brain tubulin with a dissociation constant of 4.1+/-0.9 microM. It inhibited microtubule assembly and increased the GTP hydrolysis rate of microtubule assembly. The compound did not alter the binding of 2'(or 3')-O-(trinitrophenyl) guanosine 5'-triphosphate (TNP-GTP), a fluorescent analogue of GTP, to tubulin suggesting that it did not inhibit the binding of GTP to tubulin. However, we obtained evidence indicating that HMBA perturbed the conformation of the GTP binding site in tubulin. In addition, an analysis of the modified Dixon plot suggested that HMBA competitively inhibited the binding of colchicine to tubulin. A computational analysis of the binding of HMBA to tubulin supported the finding that HMBA shared its binding site with colchicine in tubulin and indicated that the binding of HMBA to tubulin was primarily stabilized through hydrogen bonding. PMID- 20302848 TI - Exploring death receptor pathways as selective targets in cancer therapy. AB - A recent and innovative strategy in cancer therapy is the activation of apoptosis in tumour cells specifically expressing death receptors (DR) belonging to the tumour necrosis factor (TNF) receptor superfamily and including several members known since the early '90. Among these, those largely studied for clinical purpose are TNF, CD95, and TRAIL receptors. Promising results are expecting from ongoing phases I/II clinical trials proving the therapeutic efficacy of DR agonistic antibodies and/or recombinant proteins alone or in association to classic and novel chemotherapeutic drugs. However, two key issues need extensive studies, before clinical and safe applications of DRs as effective anticancer drugs can be accepted: i. DR-based cancer therapy must be selective and effective against a broad range of cancers and reduce excessive systemic toxicity toward normal cells and tumour resistance after recurrent treatments; ii. an improved knowledge of mechanisms of alternative signalling triggered by DR ligands and leading to cell survival and apoptotic resistance. Activation of survival pathways regulated by key factors, such as NF-kappaB, JNK, p38, ERK and PI(3)K are the focus of several studies revealing the dark side of DR signalling. The present review focuses on new insights in the signalling and clinical application of TNF, CD95 and TRAIL receptors. PMID- 20302849 TI - Role of midbrain periaqueductal gray P2X3 receptors in electroacupuncture mediated endogenous pain modulatory systems. AB - Extracellular ATP facilitates pain transmission at peripheral and spinal sites via the P2X receptors and the P2X3 subtype is an important candidate for this effect. Electroacupuncture (EA) has been clinically utilized to manage chronic pain. In this study, with neuropathic pain model of Sprague-Dawley (SD) rats, the P2X3 receptor protein level and expression location in the midbrain periaqueductal gray (PAG), a crucial site in endogenous pain modulatory system, were evaluated by Western blotting and immunohistochemistry. The results showed (1) pain thresholds were decreased while P2X3 receptor expression was up regulated in the lateral PAG (lPAG) when neuropathic pain occurred. When the lPAG was pretreated with P2X3 receptors, antagonist A-317491 attenuated the antinociceptive effect produced by intra-lPAG injection of alpha,beta-methylene ATP (alpha, beta-meATP), an agonist for P2X3 receptor. (2) Multiple EA treatments begot enhanced pain thresholds and increased P2X3 receptor immunoreactivity in the lPAG in neuropathic pain rats. Conversely, the down-regulated P2X3 receptor expression in the lPAG with antisense oligodeoxynucleotide (ODN) for P2X3 gene significantly attenuated the antinociceptive effect of EA treatment. These results suggest that P2X3 receptors in the lPAG play an inhibitory role in pain modulation and EA exerts a marked therapeutic effect in relieving neuropathic pain in CCI rats, which may be related to its regulative effect on the expression of P2X3 receptors in the lPAG. In conclusion, P2X3 receptors in the lPAG are involved in the supraspinal antiociception effect of EA treatment. PMID- 20302850 TI - Hippocampal expression and distribution of CB1 receptors in the Amazonian rodent Proechimys: an animal model of resistance to epilepsy. AB - Proechimys, a rodent living in the Amazon region, has shown resistance to developing chronic epilepsy when submitted to different experimental models. Recently, many studies have attributed a potent anticonvulsant action to cannabinoid receptor CB1. This study investigated the distribution and expression of the CB1 receptor in the hippocampal formation of Proechimys using immunohistochemistry and Western blotting techniques. Results were compared with values obtained from adult Wistar rats. The immunoreactivity for CB1 was evident throughout the Ammon's horn and in the hilar region of both animal species. However, the distribution of these receptors was higher in the stratum lucidum of CA3 and in the hilar region of Proechimys. In addition, higher expression of CB1 receptors was observed in the Proechimys hippocampus. These data could explain, at least partially, the natural resistance of this animal species to developing spontaneous seizures following epileptogenic precipitating events. PMID- 20302851 TI - Tumor promotion by copper-overloading and its enhancement by excess iron accumulation involving oxidative stress responses in the early stage of a rat two stage hepatocarcinogenesis model. AB - To investigate liver tumor promotion mechanisms of copper (Cu)- and iron (Fe) overloading, immunolocalization of metal-related biomolecules and lipid peroxidation end products was examined in preneoplastic liver cell foci that expressed glutathione S-transferase placental form (GST-P) in early-stage tumor promotion over 6 weeks in a rat two-stage hepatocarcinogenesis model. Gene expression and concentrations of thiobarbituric acid-reactive substance (TBARS) in the liver were also analyzed. Cu-overloading alone exerted a weak promoting activity, which was enhanced by Fe-overloading. By Cu-overloading, GST-P(+) foci that co-expressed transferrin receptors or downregulated ceruloplasmin increased, suggesting preneoplastic lesion-specific enhancement of oxidative cellular stress. Cu-overloading also increased transcripts of antioxidant enzymes (Gstm3 and Gst Yc2 subunit), cell proliferation, and numbers of single liver cells expressing GST-P or heme oxygenase-1 (HO-1) in the liver, suggesting that oxidative stress induces single-cell toxicity, with the ensuing regeneration contributing to tumor promotion. Fe-overloading increased liver TBARS and HO-1 expressing Kupffer cells, the latter suggesting protection against inflammatory stimuli causing fluctuating proinflammatory cytokine mRNA levels. By co overloading of Cu and Fe, Cu-overload-related single liver cell toxicity and regeneration increased, as did cytokine imbalances involving increased cyclooxygenase-2-producing Kupffer cells and accumulation of malondialdehyde within GST-P(+) foci. These results suggest an involvement of oxidative stress responses in Cu-induced tumor promotion and Fe-induced enhancement by increasing cytokine imbalances and GST-P(+) foci-specific lipid peroxidation. PMID- 20302852 TI - Melatonin protects the cytochrome P450 system through a novel antioxidant mechanism. AB - Melatonin, an endogenous hormone, is used as an antioxidant drug in doses quite higher than the endogenous circulating levels of this hormone. Hepatic endoplasmic reticulum contains the cytochrome P450 (CYP450) system, which catalyzes one biotransformation pathway of melatonin; this organelle is also one of the main sources of reactive oxygen species in cells. Therefore, we proposed that the antioxidant activity of this hormone may have a biological relevance in the organelle where it is biotransformed. To evaluate this postulate, we used Fe(3+)/ascorbate, an oxygen free radical generating system that leads to lipid peroxidation, loss of protein-thiol content, and activation of UDP glucuronyltransferase in rat liver microsomes. We found that mM concentrations of melatonin prevented all these oxidative phenomena. We also found that Fe(3+)/ascorbate leads to structural alterations in the CYP450 monooxygenase, the enzyme that binds the substrate in the CYP450 system catalytic cycle, probably through direct oxidation of the protein, and also inhibited p-nitroanisole O demethylation, a reaction catalyzed by the CYP450 system. Notably, melatonin prevented both phenomena at microM concentrations. We provide evidence suggesting that melatonin may be oxidized by oxygen free radicals. Thus, we postulate that melatonin may be acting as an oxygen free radical scavenger, and Fe(3+)/ascorbate modified melatonin would be directly protecting the CYP450 system through an additional specific mechanism. Pharmacological relevance of this phenomenon is discussed. PMID- 20302853 TI - Redox status of the liver and kidney of 2,2-dichlorovinyl dimethyl phosphate (DDVP) treated rats. AB - The effect of 2,2-dichlorovinyl dimethyl phosphate on redox homeostasis in male rats was investigated. Rats were grouped into four: A, B, C and D where A (the control) received orally 1 ml of distilled water; B, C and D (test groups) received orally 2.5, 5 and 10mg/kg body weight of DDVP respectively for 28 days. DDVP administration significantly reduced (P<0.05) the alkaline phosphatase activity in the liver and kidney with corresponding increases in the serum. Acid phosphatase activity increased significantly (P<0.05) in liver and kidney, while there was no significant change (P>0.05) in the serum acid phosphatase activity. There was also a significant decrease (P<0.05) in the activities of superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase in the liver and kidney. Liver and kidney levels of GSH, vitamins C and E were also significantly reduced (P<0.05). Serum malonidialdehyde and lipid hydroperoxide also increased significantly (P<0.05) in all DDVP treated groups. The available data from this study revealed that DDVP brings about its toxicity through depletion of the antioxidant systems and thus exposing the cells and cellular macromolecules to oxidative attacks by reactive oxygen species generated either from its metabolites or other in vivo means. PMID- 20302854 TI - Mycophenolic acid inhibits the phosphorylation of NF-kappaB and JNKs and causes a decrease in IL-8 release in H2O2-treated human renal proximal tubular cells. AB - Ischaemia-reperfusion injury is a common occurrence in renal transplantation and may affect the long-term survival of the allograft. Oxidative stress may play a crucial role in this, with reactive oxygen species formed during reperfusion causing direct cellular damage as well as activating pro-inflammatory pathways. A human proximal tubule cell line (HK-2) was subjected to hydrogen peroxide (H(2)O(2)) stress that resulted in phosphorylation of c-jun N-terminal kinases (JNKs) and the transcription factor NF-kappaB at Ser276, both of which have been associated with inflammation. Interleukin (IL)-8 production also increased upon H(2)O(2) stimulation. Pre-incubation of the cells with mycophenolic acid (MPA) resulted in reduced phosphorylation of both JNKs and NF-kappaB, and reduced IL-8 release in H(2)O(2)-stimulated HK-2 cells. MPA also reduced the H(2)O(2)-induced phosphorylation of p38 MAP (mitogen-activated protein) kinase, the extracellular signal regulated kinase 1/2 (ERK1/2), Akt kinase and the transcription factor CREB (cyclic AMP response element binding protein). In rat kidneys subjected to ischaemia-reperfusion, an increase in both pJNK1/2 and pNF-kappaB was observed, which was reduced in kidneys obtained from mycophenolate mofetil (MMF)-treated rats. These results suggest that MPA may inhibit pro-inflammatory responses in the kidney by inhibiting activation of pro-inflammatory molecules in both the kidney and human renal proximal tubular cells subjected to oxidative stress. PMID- 20302855 TI - Ubiquitin specific proteases USP24 and USP40 and ubiquitin thiolesterase UCHL1 polymorphisms have synergic effect on the risk of Parkinson's disease among Taiwanese. AB - BACKGROUND: Impaired ubiquitin-proteasome system function may contribute to the pathogenesis of Parkinson's disease (PD). METHODS: We conducted a case-control study in a cohort of 517 PD cases and 518 ethnically matched controls to investigate the association of ubiquitin specific proteases USP24 rs487230 C>T, USP40 rs1048603 C>T, and ubiquitin thiolesterase UCHL1 rs5030732 A>C polymorphisms with the risk of PD. RESULTS: No significant difference in the genotype or allele distribution was found between PD and controls. After stratification by age, the genotype and allele frequencies of USP24 rs487230 are significantly different between PD and controls >or=60 years of age (P=0.035 and 0.013, respectively). Multivariable logistic regression with adjusting for onset age and sex showed that, in a dominant model, USP24 T-carrying genotype was associated with risk reduction in developing PD in individuals >or=60 years of age (OR=0.61; 95% CI=0.41-0.90, P=0.010). This is also true for T allele (OR=0.64; 95% CI=0.44-0.91, P=0.023). When examining the interaction between genes on PD risk without age stratification, the protective effect of USP24 CT/TT genotype on PD risks was strengthened by the USP40 T-carrying genotype (OR=0.42; 95% CI=0.22-0.81, P=0.009) and UCHL1 C-carrying genotype (OR=0.67; 95% CI=0.47 0.97, P=0.032). CONCLUSIONS: Our results suggest that USP24 alone plays a role in PD susceptibility among Taiwanese people >or=60 years of age, or acting synergistically with USP40 and UCHL1 in the total subjects. PMID- 20302856 TI - Endocannabinoids and pregnancy. AB - Acylethanolamides such as anandamide (AEA), and monoacylglycerols like 2 arachidonoylglycerol are endocannabinoids that bind to cannabinoid, vanilloid and peroxisome proliferator-activated receptors. These compounds, their various receptors, the purported membrane transporter(s), and related enzymes that synthesize and degrade them are collectively referred to as the "endocannabinoid system (ECS)". Poorly defined cellular and molecular mechanisms control the biological actions of the ECS. Over the last decade evidence has been emerging to suggest that the ECS plays a significant role in various aspects of human reproduction. In this review, we summarize our current understanding of this role especially the involvement of AEA and related ECS elements in regulating oogenesis, embryo oviductal transport, blastocyst implantation, placental development and pregnancy outcomes, and sperm survival, motility, capacitation and acrosome reaction. Additionally, the possibility that plasma and tissue AEA and other cannabinoids may represent reliable diagnostic markers of natural and assisted reproduction and pregnancy outcomes in women will be discussed. PMID- 20302858 TI - Characterization of various promoter regions of the human DNA helicase-encoding genes and identification of duplicated ets (GGAA) motifs as an essential transcription regulatory element. AB - DNA helicases are important in the regulation of DNA transaction and thereby various cellular functions. In this study, we developed a cost-effective multiple DNA transfection assay with DEAE-dextran reagent and analyzed the promoter activities of the human DNA helicases. The 5'-flanking regions of the human DNA helicase-encoding genes were isolated and subcloned into luciferase (Luc) expression plasmids. They were coated onto 96-well plate and used for co transfection with a renilla-Luc expression vector into various cells, and dual Luc assays were performed. The profiles of promoter activities were dependent on cell lines used. Among these human DNA helicase genes, XPB, RecQL5, and RTEL promoters were activated during TPA-induced HL-60 cell differentiation. Interestingly, duplicated ets (GGAA) elements are commonly located around the transcription start sites of these genes. The duplicated GGAA motifs are also found in the promoters of DNA replication/repair synthesis factor genes including PARG, ATR, TERC, and Rb1. Mutation analyses suggested that the duplicated GGAA motifs are necessary for the basal promoter activity in various cells and some of them positively respond to TPA in HL-60 cells. TPA-induced response of 44-bp in the RTEL promoter was attenuated by co-transfection of the PU.1 expression vector. These findings suggest that the duplicated ets motifs regulate DNA-repair associated gene expressions during macrophage-like differentiation of HL-60 cells. PMID- 20302857 TI - Regulation of EGFR and Notch signaling by distinct isoforms of D-cbl during Drosophila development. AB - Cells receive and interpret extracellular signals to regulate cellular responses such as proliferation, cell survival and differentiation. However, proper inactivation of these signals is critical for appropriate homeostasis. Cbl proteins are E3-ubiquitin ligases that restrict receptor tyrosine kinase (RTK) signaling, most notably EGFR (Epidermal Growth Factor Receptor), via the endocytic pathway. Consistently, many mutant phenotypes of Drosophila cbl (D-cbl) are due to inappropriate activation of EGFR signaling. However, not all D-cbl phenotypes can be explained by increased EGFR activity. Here, we report that D Cbl also negatively regulates Notch activity during eye and wing development. D cbl produces two isoforms by alternative splicing. The long isoform, D-CblL, regulates the EGFR. We found that the short isoform, D-CblS, preferentially restricts Notch signaling. Specifically, our data imply that D-CblS controls the activity of the Notch ligand Delta. Taken together, these data suggest that D-Cbl controls the EGFR and Notch/Delta signaling pathways through production of two alternatively spliced isoforms during development in Drosophila. PMID- 20302859 TI - Remodeling of nuclear architecture by the thiodioxoxpiperazine metabolite chaetocin. AB - Extensive changes of higher order chromatin arrangements can be observed during prometaphase, terminal cell differentiation and cellular senescence. Experimental systems where major reorganization of nuclear architecture can be induced under defined conditions, may help to better understand the functional implications of such changes. Here, we report on profound chromatin reorganization in fibroblast nuclei by chaetocin, a thiodioxopiperazine metabolite. Chaetocin induces strong condensation of chromosome territories separated by a wide interchromatin space largely void of DNA. Cell viability is maintained irrespective of this peculiar chromatin phenotype. Cell cycle markers, histone signatures, and tests for cellular senescence and for oxidative stress indicate that chaetocin induced chromatin condensation/clustering (CICC) represents a distinct entity among nuclear phenotypes associated with condensed chromatin. The territorial organization of entire chromosomes is maintained in CICC nuclei; however, the conventional nuclear architecture harboring gene-dense chromatin in the nuclear interior and gene-poor chromatin at the nuclear periphery is lost. Instead gene dense and transcriptionally active chromatin is shifted to the periphery of individual condensed chromosome territories where nascent RNA becomes highly enriched around their outer surface. This chromatin reorganization makes CICC nuclei an attractive model system to study this border zone as a distinct compartment for transcription. Induction of CICC is fully inhibited by thiol dependent antioxidants, but is not related to the production of reactive oxygen species. Our results suggest that chaetocin functionally impairs the thioredoxin (Trx) system, which is essential for deoxynucleotide synthesis, but in addition involved in a wide range of cellular functions. The mechanisms involved in CICC formation remain to be fully explored. PMID- 20302860 TI - Heparin II domain of fibronectin mediates contractility through an alpha4beta1 co signaling pathway. AB - In the trabecular meshwork (TM) of the eye, regulation of tissue contractility by the PPRARI sequence within the Heparin II (HepII) domain of fibronectin is believed to control the movement of aqueous humor and dictate the level of intraocular pressure. This study shows that the HepII domain utilizes activated alpha4beta1 integrin and collagen to mediate a co-signaling pathway that down regulates contractility in TM cells. siRNA silencing of alpha4beta1 integrin blocked the actin disrupting effects of both PPRARI and the HepII domain. The down-regulation of the actin cytoskeleton and contractility did not involve syndecan-4 or other heparan sulfate proteoglycans (HSPGs) since siRNA silencing of syndecan-4 expression or heparitinase removal of cell surface HSPGs did not prevent the HepII-mediated disruption of the actin cytoskeleton. HepII-mediated disruption of the cytoskeleton depended upon the presence of collagen in the extracellular matrix, and cell binding studies indicated that HepII signaling involved cross-talk between alpha4beta1 and alpha1/alpha2beta1 integrins. This is the first time that the PPRARI sequence in the HepII domain has been shown to serve as a physiological alpha4beta1 ligand, suggesting that alpha4beta1 integrin may be a key regulator of tissue contractility. PMID- 20302861 TI - Choroidal blood flow compensation in rats for arterial blood pressure decreases is neuronal nitric oxide-dependent but compensation for arterial blood pressure increases is not. AB - Choroidal blood flow (ChBF) compensates for changes in arterial blood pressure (ABP) and thereby remains relatively stable within a +/-40 mmHg range of basal ABP in rabbits, humans and pigeons. In the present study, we investigated if ChBF can compensate for increases and decreases in ABP in rats. ChBF was continuously monitored using laser Doppler flowmetry in anesthetized rats, and ABP measured via the femoral artery. At multiple intervals over a 2-4 h period during which ABP varied freely, ChBF and ABP were sampled and the results compiled across rats. We found that ChBF remained near baseline over an ABP range from 40 mmHg above basal ABP (90-100 mmHg) to 40 mmHg below basal ABP, but largely followed ABP linearly below 60 mmHg. Choroidal vascular resistance increased linearly as BP increased above 100 mmHg, and decreased linearly as BP declined from basal to 60 mmHg, but resistance declined no further below 60 mmHg. Inhibition of nitric oxide (NO) formation by either a selective inhibitor of neuronal nitric oxide synthase (NOS) (N(omega)-propyl-L-arginine) or a nonselective inhibitor of both neuronal NOS and endothelial NOS (N(omega)-nitro-l-arginine methyl ester) did not affect compensation above 100 mmHg ABP, but did cause ChBF to linearly follow declines in BP below 90 mmHg. In NOS-inhibited rats, vascular resistance increased linearly with BP above 100 mmHg, but remained at baseline below 90 mmHg. These findings reveal that ChBF in rats, as in rabbits, humans and pigeons, compensates for rises and/or declines in arterial blood pressure so as to remain relatively stable within a physiological range of ABPs. The ChBF compensation for low ABP in rats is dependent on choroidal vasodilation caused by neuronal NO formation but not the compensation for elevated BP, implicating parasympathetic nervous system vasodilation in the ChBF compensation to low ABP. PMID- 20302863 TI - Confocal microscopy of giant vesicles supports the absence of HIV-1 neutralizing 2F5 antibody reactivity to plasma membrane phospholipids. AB - The broadly neutralizing anti-HIV-1 2F5 monoclonal antibody recognizes a gp41 epitope proximal to the viral membrane. Potential phospholipid autoreactivity at cell surfaces has raised concerns about the use of this antibody for development of vaccines or immunotherapy. In this study, confocal microscopy of giant unilamellar vesicles (GUVs) was used to assess 2F5 reactivity with phospholipids assembled into bilayers with surface charge and curvature stress approximating those of the eukaryotic plasma membranes. Antibody partitioning into lipid bilayers required the specific recognition of membrane-inserted epitope, indicating that 2F5 was unable to directly react with GUV phospholipids, even under fluid phase segregation conditions. Our results thus support the feasibility of raising 2F5-like neutralizing responses through vaccination, and the medical safety of mAb infusions. PMID- 20302864 TI - Phospholipid scramblase: an update. AB - The best understood consequence of the collapse of lipid asymmetry is exposure of phosphatidylserine (PS) in the external leaflet of the plasma membrane bilayer, where it is known to serve at least two major functions: providing a platform for development of the blood coagulation cascade and presenting the signal that induces phagocytosis of apoptotic cells. Lipid asymmetry is collapsed by activation of phospholipid scramblase(s) that catalyze bidirectional transbilayer movement of the major classes of phospholipid. The protein corresponding to this activity is not yet known. Observations on cells from patients with Scott syndrome, a rare hereditary bleeding disorder resulting from impaired lipid scrambling, have shown that there are multiple activation pathways that converge on scramblase activity. PMID- 20302862 TI - Task-specificity vs. ceiling effect: step-training in shallow water after spinal cord injury. AB - While activity-based rehabilitation is one of the most promising therapeutic approaches for spinal cord injury, the necessary components for optimal locomotor retraining have not yet been determined. Currently, a number of different activity-based approaches are being investigated including body weight-supported treadmill training (with and without manual assistance), robotically-assisted treadmill training, bicycling and swimming, among others. We recently showed, in the adult rat, that intensive rehabilitation based on swimming brought about significant improvements in hindlimb performance during swimming but did not alter the normal course of recovery of over-ground walking (Smith et al., 2006a,b, 2009). However, swimming lacks the phasic limb-loading and plantar cutaneous feedback thought to be important for weight-supported step training. So, we are investigating an innovative approach based on walking in shallow water where buoyancy provides some body weight support and balance while still allowing for limb-loading and appropriate cutaneous afferent feedback during retraining. Thus, the aim of this study is to determine if spinal cord injured animals show improved overground locomotion following intensive body weight-supported locomotor training in shallow water. The results show that training in shallow water successfully improved stepping in shallow water, but was not able to bring about significant improvements in overground locomotion despite the fact that the shallow water provides sufficient body weight support to allow acutely injured rats to generate frequent plantar stepping. These observations support previous suggestions that incompletely injured animals retrain themselves while moving about in their cages and that daily training regimes are not able to improve upon this already substantial functional improvement due to a ceiling effect, rather than task-specificity, per se. These results also support the concept that moderately-severe thoracic contusion injuries decrease the capacity for body weight support, but do not decrease the capacity for pattern generation. In contrast, animals with severe contusion injuries could not support their body weight nor could they generate a locomotor pattern when provided with body weight support via buoyancy. PMID- 20302866 TI - Genome-wide association studies: present status and future directions. PMID- 20302867 TI - Understanding differences in the guidelines for colorectal cancer screening. AB - In this issue of Gastroenterology, the editors present 2 expert perspectives on the colorectal screening guidelines published in the May 2008 issue of the journal. PMID- 20302871 TI - Characterization of a novel octopamine receptor expressed in the surf clam Spisula solidissima. AB - We have cloned and sequenced a cDNA from the surf clam (Spisula solidissima, a pelecypod mollusc) that encodes an octopamine receptor which we have named Spi OAR. The sequence of Spi-OAR shares many similarities with two Aplysia and three Drosophila octopamine receptors belonging to a sub-group of beta-adrenergic-like octopamine receptors. Using an expression vector and transient transfections of Spi-OAR into HEK 293 cells, we observed an increase of cAMP upon addition of octopamine and, to a lesser extent, of tyramine, but not after addition of dopamine, serotonin, or histamine. Using a battery of known agonists and antagonists for octopamine receptors, we observed a rather unique pharmacological profile for Spi-OAR through measurements of cAMP. Spi-OAR exhibited some constitutive activity in HEK 293 cells and no Ca(2+) responses could be detected following addition of octopamine to Spi-OAR-transfected cells. RT-PCR analysis revealed ubiquitous expression of Spi-OAR mRNA in all adult tissues, oocytes and early embryos examined. While addition of serotonin to isolated clam oocytes resulted in meiotic activation, similar additions of octopamine had no effect, suggesting that its potential role in clam reproductive physiology differs significantly from that of serotonin. This work identifies Spi-OAR as a novel mollusc octopamine receptor closely related to other invertebrate beta-adrenergic like octopamine receptors, with possible reproductive and other physiological functions. This initial characterization of Spi-OAR makes possible further investigations and comparisons with more studied and familiar insect or gastropod mollusc octopamine receptors. PMID- 20302872 TI - Psychopathic personality traits and cortisol response to stress: the role of sex, type of stressor, and menstrual phase. AB - Previous research indicates that psychopathic personality traits are associated with lower cortisol secretion in response to stress in men but not in women. The current study explored whether prior null results for women were related to the latency of the cortisol stress response to two different types of stressors. Additionally, accuracy of self-reported menstrual phase was explored via salivary progesterone levels. A mixed-sex sample of 145 participants characterized by high (36 men, 37 women) and low (34 men, 38 women) scores on a screening measure of psychopathic personality traits were randomly assigned to either a performance based stressor task or a social rejection stressor task. Salivary hormone samples were taken just prior to task onset (baseline) and at 0, 20, 40, and 60 min post stressor. Results indicated that both men and women characterized by psychopathic personality traits exhibited lower stress-induced cortisol levels to the performance-based task in comparison with controls at 20 min post-stressor. The social rejection task produced a cortisol response 20 min post-stressor in the male controls only. Removal of women with low progesterone from the analyses strengthened the psychopathy group differences. Results could suggest that deficient cortisol production in response to stress might be another important neurobiological feature associated with psychopathic traits, and that biological verification of menstrual phase is an important aspect to obtaining accurate cortisol results in women. PMID- 20302873 TI - A new ELISA plate based microtiter well assay for mycobacterial topoisomerase I for the direct screening of enzyme inhibitory monoclonal antibody supernatants. AB - Antigen specific monoclonal antibodies present in crude hybridoma supernatants are normally screened by ELISA on plates coated with the relevant antigen. Screening for inhibitory monoclonals to enzymes would require the evaluation of purified antibodies or antibody containing supernatants for their inhibition of enzyme activity in a separate assay. However, screening for inhibitory antibodies against DNA transacting enzymes such as topoisomerase I (topo I) cannot be done using hybridoma supernatants due to the presence of nucleases in tissue culture media containing foetal calf serum which degrade the DNA substrates upon addition. We have developed a simple and rapid screening procedure for the identification of clones that secrete inhibitory antibodies against mycobacterial topo I using 96 well ELISA microtiter plates. The principle of the method is the selective capture of monoclonal antibodies from crude hybridoma supernatants by topo I that is tethered to the plate through the use of plate-bound polyclonal anti-topo I antibodies. This step allows the nucleases present in the medium to be washed off leaving the inhibitor bound to the tethered enzyme. The inhibitory activity of the captured antibody is assessed by performing an in situ DNA relaxation assay by the addition of supercoiled DNA substrate directly to the microtiter well followed by the analysis of the reaction products by agarose gel electrophoresis. The validity of this method was confirmed by purification of the identified inhibitory antibody and its evaluation in a DNA relaxation assay. Elimination of all enzyme-inhibitory constituents of the culture medium from the well in which the inhibitory antibody is bound to the tethered enzyme may make this method broadly applicable to enzymes such as DNA gyrases, restriction enzymes and other DNA transaction enzymes. Further, the method is simple and avoids the need of prior antibody purification for testing its inhibitory activity. PMID- 20302874 TI - An optimized assay for the enumeration of antigen-specific memory B cells in different compartments of the human body. AB - OBJECT: In the framework of our current study we set out to develop an optimized assay for the quantification of antigen-specific B cells in different compartments of the human body. METHODS: Mononuclear cells (MNC) derived from the peripheral blood, bone marrow (BM), or human tonsils were incubated with different combinations of stimuli. The stimulated cells and culture supernatants were then applied to IgG-ELISPOT and ELISA read-out assays and tetanus toxoid (TT)-specific B cell responses were quantified. RESULTS: We found that a combination of CD40L, CpG, and IL21 was optimal for the induction of TT-specific IgG-producing cells from memory B cell (mBc) precursors. This cocktail of stimuli led to a proliferation-dependent induction of CD19(intermediate)CD38(high)CD138(high)IgD(negative) terminally differentiated plasma cells. Applying our optimized methodology we were also able to quantify mBc specific for cytomegalovirus and influenza virus A. Most importantly, the same method proved useful for the comparison of mBc frequencies between different compartments of the body and, accordingly, we were able to demonstrate that TT specific mBc preferably reside within tonsillar tissue. CONCLUSION: Here, we optimized an assay for the quantification of antigen-specific B cells in different human tissues demonstrating, for example, that TT-specific mBc preferably reside in human tonsils but not in the BM or the peripheral blood. We suggest that our approach can be used for the enumeration of mBc specific for a wide variety of Ag (microbial, tumor-related, auto-antigens), which will lead to significant improvements regarding our knowledge about the biology of humoral immunity. PMID- 20302875 TI - The human CASQ2 mutation K206N is associated with hyperglycosylation and altered cellular calcium handling. AB - Mutations in the human cardiac calsequestrin gene (CASQ2) are linked to catecholaminergic polymorphic ventricular tachycardia (CPVT-2). This inherited disorder is characterized by life-threatening arrhythmias induced by physical and emotional stress in young patients. Here we identified a novel heterozygous missense mutation (K206N) in the CASQ2 gene in a symptomatic family in which one member died of cardiac arrest. The functional properties of CSQ(K206N) were investigated in comparison to the wild-type form of CASQ2 (CSQ(WT)) by expression in eukaryotic cell lines and neonatal mouse myocytes. The mutation created an additional N-glycosylation site resulting in a higher molecular weight form of the recombinant protein on immunoblots. The mutation reduced the Ca(2+) binding capacity of the protein and exhibited an altered aggregation state. Consistently, CSQ(K206N)-expressing myocytes exhibited an impaired response to caffeine administration, suggesting a lower Ca(2+) load of the sarcoplasmic reticulum (SR). The interaction of the mutated CSQ with triadin and the protein levels of the ryanodine receptor were unchanged but the maximal specific [(3)H]ryanodine binding was increased in CSQ(K206N)-expressing myocytes, suggesting a higher opening state of the SR Ca(2+) release channel. Myocytes with expression of CSQ(K206N) showed a higher rate of spontaneous SR Ca(2+) releases under basal conditions and after beta-adrenergic stimulation. We conclude that CSQ(K206N) caused a reduced Ca(2+) binding leading to an abnormal regulation of intracellular Ca(2+) in myocytes. This may then contribute to the increased propensity to trigger spontaneous Ca(2+) transients in CSQ(K206N)-expressing myocytes. PMID- 20302876 TI - Differential regulation of TNF receptors by vagal nerve stimulation protects heart against acute ischemic injury. AB - Vagal nerve stimulation (VS) has been reported to improve the survival after both acute and chronic myocardial infarction through the release of neurotransmitter ACh. However, the precise mechanism behind its beneficial effect is still unknown. In this study, we demonstrate the upregulation of tumor necrosis factor alpha (TNF-alpha) and its cell survival TNF receptor-2 (TNFR2) as the mechanism behind VS induced myocardial protection. We investigated the effects of efferent VS on myocardial ischemic injury with in vivo and in vitro mouse models. In in vivo hearts VS significantly increased the expression of TNF-alpha both at the messenger and protein level after 3-hours of myocardial ischemia. In the in vitro studies ACh treatment before hypoxia, induced a significant upregulation of TNF alpha compared to the untreated cardiomyocytes. Immunofluorescence analysis confirmed the synthesis of TNF-alpha by cardiomyocytes both in vivo and in vitro. VS also significantly reduced the myocardial infarct size (23.9+/-5.7% vs. 56+/ 1.9%) and activated the cell survival Akt cascade system. Further, ACh upregulated the cell survival TNFR2 expression, while downregulating the cell destructive TNF receptor 1 (TNFR1) expression. These results were confirmed using the TNF receptors deficient mice, where the VS mediated protection was lost both in vivo and in vitro in TNFR2 (TNFR2(-/-)) and TNF receptors double knock out (TNFR1(-/-)2(-/-)) mice. VS and ACh protects the heart against acute ischemia or hypoxic injury by differentially regulating the TNF receptor subtypes. PMID- 20302877 TI - NMR solution structure and DNA-binding model of the DNA-binding domain of competence protein A. AB - Competence protein A (ComA) is a response regulator protein involved in the development of genetic competence in the Gram-positive spore-forming bacterium Bacillus subtilis, as well as the regulation of the production of degradative enzymes and antibiotic synthesis. ComA belongs to the NarL family of proteins, which are characterized by a C-terminal transcriptional activator domain that consists of a bundle of four helices, where the second and third helices (alpha 8 and alpha 9) form a helix-turn-helix DNA-binding domain. Using NMR spectroscopy, the high-resolution 3D solution structure of the C-terminal DNA-binding domain of ComA (ComAC) has been determined. In addition, surface plasmon resonance and NMR protein-DNA titration experiments allowed for the analysis of the interaction of ComAC with its target DNA sequences. Combining the solution structure and biochemical data, a model of ComAC bound to the ComA recognition sequences on the srfA promoter has been developed. The model shows that for DNA binding, ComA uses the conserved helix-turn-helix motif present in other NarL family members. However, the model reveals also that ComA might use a slightly different part of the helix-turn-helix motif and there appears to be some associated domain re orientation. These observations suggest a basis for DNA binding specificity within the NarL family. PMID- 20302878 TI - Structural and functional analysis of the engineered type I DNA methyltransferase EcoR124I(NT). AB - The Type I R-M system EcoR124I is encoded by three genes. HsdM is responsible for modification (DNA methylation), HsdS for DNA sequence specificity and HsdR for restriction endonuclease activity. The trimeric methyltransferase (M(2)S) recognises the asymmetric sequence (GAAN(6)RTCG). An engineered R-M system, denoted EcoR124I(NT), has two copies of the N-terminal domain of the HsdS subunit of EcoR124I, instead of a single S subunit with two domains, and recognises the symmetrical sequence GAAN(7)TTC. We investigate the methyltransferase activity of EcoR124I(NT), characterise the enzyme and its subunits by analytical ultracentrifugation and obtain low-resolution structural models from small-angle neutron scattering experiments using contrast variation and selective deuteration of subunits. PMID- 20302879 TI - Key amino acid residues involved in multi-point binding interactions between brazzein, a sweet protein, and the T1R2-T1R3 human sweet receptor. AB - The sweet protein brazzein [recombinant protein with sequence identical with the native protein lacking the N-terminal pyroglutamate (the numbering system used has Asp2 as the N-terminal residue)] activates the human sweet receptor, a heterodimeric G-protein-coupled receptor composed of subunits Taste type 1 Receptor 2 (T1R2) and Taste type 1 Receptor 3 (T1R3). In order to elucidate the key amino acid(s) responsible for this interaction, we mutated residues in brazzein and each of the two subunits of the receptor. The effects of brazzein mutations were assayed by a human taste panel and by an in vitro assay involving receptor subunits expressed recombinantly in human embryonic kidney cells; the effects of the receptor mutations were assayed by in vitro assay. We mutated surface residues of brazzein at three putative interaction sites: site 1 (Loop43), site 2 (N- and C-termini and adjacent Glu36, Loop33), and site 3 (Loop9 19). Basic residues in site 1 and acidic residues in site 2 were essential for positive responses from each assay. Mutation of Y39A (site 1) greatly reduced positive responses. A bulky side chain at position 54 (site 2), rather than a side chain with hydrogen-bonding potential, was required for positive responses, as was the presence of the native disulfide bond in Loop9-19 (site 3). Results from mutagenesis and chimeras of the receptor indicated that brazzein interacts with both T1R2 and T1R3 and that the Venus flytrap module of T1R2 is important for brazzein agonism. With one exception, all mutations of receptor residues at putative interaction sites predicted by wedge models failed to yield the expected decrease in brazzein response. The exception, hT1R2 (human T1R2 subunit of the sweet receptor):R217A/hT1R3 (human T1R3 subunit of the sweet receptor), which contained a substitution in lobe 2 at the interface between the two subunits, exhibited a small selective decrease in brazzein activity. However, because the mutation was found to increase the positive cooperativity of binding by multiple ligands proposed to bind both T1R subunits (brazzein, monellin, and sucralose) but not those that bind to a single subunit (neotame and cyclamate), we suggest that this site is involved in subunit-subunit interaction rather than in direct brazzein binding. Results from this study support a multi-point interaction between brazzein and the sweet receptor by some mechanism other than the proposed wedge models. PMID- 20302880 TI - Aging-related hyperinflammation in endotoxemia is mediated by the alpha2A adrenoceptor and CD14/TLR4 pathways. AB - AIMS: Sepsis is a major cause of morbidity and mortality in the elderly population. In prior studies, we have shown that in vivo, the inflammatory response in aged animals is exaggerated as compared to young animals and that this response likely accounts for the increased morbidity and mortality. Part of this uncontrolled inflammatory response in sepsis is due to the innate immune response. However, recent studies have shown that the pathogenesis of sepsis is much more complex. The adrenergic autonomic nervous system is now thought to play a key role in modulating the inflammatory response in sepsis. In this study, we hypothesize that not only is the innate immune response enhanced in response to lipopolysaccharide (LPS) in aged animals, but that the adrenergic nervous system also plays a role in the release of excess inflammatory cytokines. MAIN METHODS: Male Fischer-344 rats (young: 3 months; aged: 24 months) were used. Endotoxemia was induced by intravenous injection of lipopolysaccharide (LPS, 15 mg/kg BW). Splenic tissues were harvested and mRNA and protein were extracted. The protein expression of CD14 and TLR4, key mediators of LPS in the innate response, as well as alpha-2A adrenergic receptor (alpha(2A)-AR) and phosphodiesterase 4D (PDE4D), as the means by which the autonomic nervous system exerts its effects were analyzed. KEY FINDINGS: Splenic tissue concentrations of alpha(2A)-AR, PDE4D, CD14, and TLR4 were significantly increased in septic aged rats as compared to aged sham rats and septic young rats. The increased expression of alpha(2A)-AR in septic aged rats was further confirmed by immunohistochemical staining of splenic tissues. SIGNIFICANCE: These data support the hypothesis that not only is the innate immune response increased in aged animals during sepsis, but that there is also an upregulated response of the adrenergic autonomic nervous system that contributes to excess proinflammatory cytokine release. PMID- 20302881 TI - Hyperglycemia attenuates acute permeability response to advanced glycation end products in retinal microvasculature. AB - Increased microvascular permeability contributes to the development of diabetic retinopathy and is associated with hyperglycemia and accumulation of advanced glycation end products (AGEs). The isolated perfused retina preparation was used to investigate the effects of hyperglycemia (HG) on the permeability response to AGEs. Retinae were dissected from rats, and the vasculature perfused with sulforhodamine B fluorescent dye and permeability of venular capillaries was determined from the rate of decrease of fluorescence gradient across a vessel during stasis. The resting permeability was very high in streptozotocin treated and some obese Zucker fatty diabetic rats, but low in others. The permeability response to glycated albumin (which is free radical-dependent) in these animals was reduced for a range of concentrations compared to the lean controls. The effects of 15 min 25 mM glucose (HG) superfusion on the retinal microvascular permeability response to 5 microM AGE-BSA was studied in non-diabetic Wistar rats. HG itself had no effect on permeability, but reduced the response to AGE BSA from 1.02+/-0.08x10(-6) cm s(-1) to 0.31+/-0.07x10(-6) cm s(-1). The response to bradykinin (also free radical-dependent) was not affected by HG. This suggests that chronic exposure to HG down-regulates the signalling pathways activated in response to RAGE stimulation. PMID- 20302882 TI - Extinction with varenicline and nornicotine, but not ABT-418, weakens conditioned responding evoked by the interoceptive stimulus effects of nicotine. AB - The interoceptive stimulus effects of nicotine acquire control over behavior. This observation, among others, suggests that the stimulus effects of nicotine are important in the development and tenacity of tobacco dependence. Despite this importance, there has been little research examining whether non-reinforced presentations (extinction) of a ligand that share stimulus effects of nicotine will weaken responding controlled by nicotine. Rats were trained to discriminate nicotine (0.4 mg/kg) from saline using a discriminated goal-tracking task in which nicotine signaled intermittent access to sucrose; sucrose was withheld on saline sessions. Experiment 1 examined substitution for nicotine by ABT-418, nornicotine, epibatidine, varenicline, or cytisine in 4-min extinction tests. Experiments 2-5 [low-dose nicotine (0.05 mg/kg), ABT-418, nornicotine, or varenicline, respectively] examined whether substitution for nicotine would persist if extinction tests were increased to 20 min and repeated daily for 6 days. Finally, generalization of this extinction back to the nicotine training stimulus was assessed. Full substitution in brief 4-min extinction tests was seen for ABT-418, nornicotine, epibatidine, varenicline, and cytisine. Low-dose nicotine, ABT-418, nornicotine, and varenicline, evoked only a partial 'nicotine like' response in the first 20-min extinction test. With repeated extinction, only low-dose nicotine, nornicotine, and varenicline continued to substitute. Extinction with nornicotine and varenicline transferred back to nicotine as indicated by a partial conditioned response to the training stimulus. Interpretations regarding 'nicotine-like' effects of a ligand depend on the nature of the test. Understanding the processes mediating transfer of extinction learning with potential pharmacotherapies may reveal new treatment targets. PMID- 20302883 TI - Synthesis of 17 alpha-substituted ethynylestradiols: potential ligands for drug vectors. AB - 17alpha-substituted ethynylestradiols, derived from estrone, were converted to their corresponding 17 alpha-(bromo- or iodo-propargyl)estrone intermediates. Nucleophilic substitution onto these moieties with malonate diester followed by hydrolysis and complexation with cis-Pt(Me(2)en)I(2) (Me(2)en=N,N dimethylethylenediamine) gave cis-Pt(Me(2)en)(2-(3-(17beta-estradiol-17 alpha-yl) prop-2-ynyl)malonato) 7, thus demonstrating that these estrogen-derived compounds can be used to synthesize stable Pt(II) complexes. The 3-(17beta-estradiol-17 alpha-yl)-prop-2-ynyl-1-sulfanylethylthiol 23 was also prepared. PMID- 20302884 TI - 2nd German-French DNA repair meeting - DNA damage and repair in ageing and degenerative diseases, Konstanz, Germany, September 20-23, 2009. AB - In September 2009, the French Society of Genetic Toxicology and the German Society for Research on DNA Repair jointly organized the '2nd German-French DNA repair meeting - DNA damage and repair in ageing and degenerative diseases', which was held in Konstanz, Germany. Here we summarize the content of the oral presentations given in the various scientific sessions and of prize-winning posters. PMID- 20302885 TI - Single particle reconstruction of membrane proteins: a tool for understanding the 3D structure of disease-related macromolecules. AB - Membrane proteins play important roles in cell functions such as neurotransmission, muscle contraction, and hormone secretion, but their structures are mostly undetermined. Several techniques have been developed to elucidate the structure of macromolecules; X-ray or electron crystallography, nuclear magnetic resonance spectroscopy, and high-resolution electron microscopy. Electron microscopy-based single particle reconstruction, a computer-aided structure determination method, reconstructs a three-dimensional (3D) structure from projections of monodispersed protein. A large number of particle images are picked up from EM films, aligned and classified to generate two-dimensional (2D) averages, and, using the Euler angle of each 2D average, reconstructed into a 3D structure. This method is challenging due to the necessity for close collaboration between classical biochemistry and innovative information technology, including parallel computing. However, recent progress in electron microscopy, mathematical algorithms, and computational ability has greatly increased the subjects that are considered to be primarily addressable using single particle reconstruction. Membrane proteins are one of these targets to which the single particle reconstruction is successfully applied for understanding of their structures. In this paper, we will introduce recently reconstructed channel-related proteins and discuss the applicability of this technique in understanding molecular structures and their roles in pathology. PMID- 20302886 TI - 2,3,7,8-Tetrachlorodibenzo-p-dioxin induces apoptosis in neural growth factor (NGF)-differentiated pheochromocytoma PC12 cells. AB - 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a potent toxicant that alters normal brain development and produces cognitive disability and motor dysfunction. However, after decades of intense study, the molecular mechanisms of TCDD-induced neurotoxicity, the signaling pathways involved and its molecular targets in neurons still remain unknown. TCDD acts as an exogenous ligand of the aryl hydrocarbon receptor (AhR) that becomes a key signaling molecule in the regulation of the toxic and carcinogenic properties of TCDD. We have used NGF differentiated pheochromocytoma (dPC12) cells to determine the type of cell death that takes place by TCDD toxicity. TCDD induced cell death in dPC12 cultures with an EC(50) of 218+/-24 nM, similar to that obtained in undifferentiated PC12 cells, 171+/-31 nM. Nuclear fragmentation was observed after TCDD incubation in parallel to an increase in caspase-3 activity. Staurosporine, which readily induced apoptosis in dPC12 cells, showed a similar increase in caspase-3 activity and the characteristic pattern of nuclear fragmentation. Flow cytometry measurements showed that dPC12 cells in the presence of TCDD were positive for annexin V labeling but negative for propidium iodide staining. In addition, TCDD increased the area of the peak corresponding to hypodiploid (apoptotic) DNA content. All together these results support the hypothesis that TCDD toxicity in dPC12 cells takes place mainly through an apoptotic process. PMID- 20302887 TI - The antiretroviral potency of emtricitabine is approximately 3-fold higher compared to lamivudine in dual human immunodeficiency virus type 1 infection/competition experiments in vitro. AB - The increasing number of antiretroviral drugs leads to mounting possibilities of combinations for the antiretroviral therapy (ART) of HIV-1 infected patients. Thus, it is of interest to determine the most potent combination of antiretroviral drugs for the first ART to delay the development of drug resistance. We have investigated the differences in the inhibitory potencies of the nucleoside reverse transcriptase inhibitors (NRTI) lamivudine (3TC) and emtricitabine (FTC) using an in vitro model based on simultaneous infection of T cells with drug-sensitive and drug-resistant viruses. Changes of frequencies in these virus populations have been measured by allele-specific real-time PCR allowing simultaneous quantification of different HIV-1 variants in the same sample. We show that the suppression of drug-sensitive viruses is significantly enhanced by FTC compared to 3TC. Mathematical modeling of the distinct rates of suppression of drug-sensitive viruses revealed an approximately 3-fold higher antiretroviral potency for FTC compared to 3TC. PMID- 20302888 TI - Biochemical and immunopathological changes in experimental neurotoxocariasis. AB - Toxocariasis is a widespread soil-transmitted parasitic disease. Toxocara canis larvae migrate through the tissues with a special predilection for the central nervous system. Recently, neurotoxocariasis is being diagnosed in humans with increasing frequency due to improved diagnostic tools. The present study aimed at exploring the biochemical and immunopathological alterations in the brain in experimental T. canis infection. For this purpose, 75 Toxocara-infected mice were sacrificed at 2, 5, and 16 weeks post-infection. The brains were removed and assayed for total larval count, pro-inflammatory cytokines (TNF-alpha, IL-6), and central neurotransmitters (gamma-aminobutyric acid, glutamate, dopamine, norepinephrine, and serotonin). Brain sections were also stained for histopathological study, and for assessment of the expression of inducible nitric oxide synthase (iNOS), and glial fibrillary acidic protein (GFAP) by immunohistochemical methods. We found that larval recovery showed progressive increase over the course of infection. Furthermore, the infected mice displayed increased expression of pro-inflammatory cytokines and iNOS, as well as significant disturbances in neurotransmitter profile. Astrocytic activation, evidenced by enhanced expression of GFAP, was also manifest in infected animals. These changes were maximal in the chronic stage of infection or intensified over time. In conclusion, experimental neurotoxocariasis is associated with significant biochemical, immunological, and pathological changes. PMID- 20302889 TI - Selection of reference genes for mRNA quantification in Trypanosoma brucei. AB - Internal normalization is an established procedure that is necessary for accurate and reliable quantification of differentially regulated mRNAs. The profound changes of gene expression in parasitic life cycles pose a particular challenge on selection of appropriate reference genes for normalization, most importantly when using quantitative real time PCR (qPCR). Here we use the ranking algorithm implemented in the geNorm application to identify suitable Trypanosoma brucei reference genes for comparisons between the bloodstream and procyclic developmental stages and for analysis of mRNA induction by environmental conditions. For these conditions, the TERT gene is a good choice for valid normalization of qPCR and is clearly superior to some other reference genes reported in the literature. For comparison of other conditions, the ranking algorithm is recommended to verify a reliable and valid normalization that is instrumental to quantitative analysis of gene expression. PMID- 20302890 TI - Identification and profiling of volatile metabolites of the biocontrol fungus Trichoderma atroviride by HS-SPME-GC-MS. AB - In the present study we describe a method, which is based on solid phase microextraction (SPME) coupled to gas chromatography-mass spectrometry (GC-MS) and which can be used for the profiling of microbial volatile organic compounds (MVOCs) in the headspace (HS) of cultures of filamentous fungi. The method comprises the following successive steps: 1. growth of the fungus on a solid culture medium directly in headspace vials, 2. measurement of volatiles by HS SPME-GC-MS, 3. deconvolution of mass spectra, 4. identification of volatiles by comparison of measured, deconvoluted mass spectra and linear temperature programmed retention indices (LTPRI) on two stationary GC phases with database entries and LTPRI published in the literature, and 5. profiling of the identified MVOCs. The developed method was successfully applied to cultures of the biocontrol fungus Trichoderma atroviride. An in-house library consisting of mass spectra and LTPRI values of fungal VOCs was established and used to study the profiles of MVOCs of this fungus. In total, 25 different MVOCs were identified by applying strict criteria (spectral match factor at least 90% and a maximum relative deviation of LTPRI of +/-2% from literature values). The MVOCs were assigned to the compound classes of alcohols, ketones, alkanes, furanes, pyrones (mainly the bioactive 6-pentyl-alpha-pyrone), mono- and sesquiterpenes, 13 of which have never been reported to be produced by Trichoderma spp. before. Eleven of these volatiles have been additionally confirmed using authentic standards. Finally, time course experiments and cultivation of T. atroviride in the presence of the mycotoxin fusaric acid demonstrated the potential of the method to study the dynamics of MVOC profiles as well as the effect of different environmental/biological conditions on the expression of MVOCs of filamentous fungi. PMID- 20302891 TI - Physical training and the dynamics of the cardiac baroreflex: a comparison when blood pressure rises and falls. AB - In the analysis of baroreceptor reflex sensitivity (BRS) through the sequence method, spontaneous cardiac sequences are sought in which systolic blood pressure (SBP) increases are accompanied by an increase in inter-beat interval (IBI) ("up" sequences), or in which a decrease in SBP is accompanied by a decrease in IBI ("down" sequences). The regression line between the SBP and the IBI values produces an estimate of BRS in ms/mm Hg. The "up" sequences are mainly associated with vagal activation and the "down" sequences with vagal inhibition. This study evaluated the effect of regular exercise on BRS assessed differentially for the "up" and "down" sequences. Thirty two regular exercisers and 27 sedentary students performed a serial arithmetic task after a baseline period. Results show that BRS in the "up" sequences was greater for the physically active group than for the sedentary group. For the physically active group, BRS in the "up" sequences was higher than BRS in the "down" sequences. The arithmetic task produced a significant BRS decrease in the "up" sequences for the physically active group but not for the sedentary group. These results show that regular exercise modulates the dynamics of the cardiac baroreflex. The differences between the "up" and "down" sequences suggest that the physically active group displays high parasympathetic cardiac control and autonomic cardiac adjustment to stressful conditions in which vagal withdrawal plays a key role in the cardiac response. PMID- 20302892 TI - Binding of dopamine and 3-methoxytyramine as l-DOPA metabolites to human alpha(2) adrenergic and dopaminergic receptors. AB - The ability of l-3,4-dihydroxyphenylalanine (l-DOPA), l-DOPA-methyl ester and their major metabolites, dopamine, dihydroxyphenylacetic acid (DOPAC), homovanillic (HVA), 3-O-methyldopa and 3-methoxytyramine (3-MT) to bind to alpha(2) adrenergic and D1 and D2 dopamine receptors was assessed by radioligand binding to cloned human receptors expressed in cell lines. As anticipated, dopamine bound with high affinity to D1 (IC(50) 1.1 + or - 0.16 microM) and D2 (IC(50) 0.7 + or - 0.3 microM) dopamine receptors. However, dopamine also bound with high affinity to alpha(2A) (IC(50) was 2.6 + or - 0.5 microM), alpha(2C) (IC(50) 3.2 + or - 0.7 microM). 3-MT bound to alpha(2A) with high affinity (IC(50), 3.6 + or - 0.2 microM) though moderate affinity to alpha(2)c, D1 and D2 receptors (values of IC(50) were 55 + or - 14, 121 + or - 43, 36 + or - 14 microM, respectively). l-DOPA-methyl ester bound with high affinity to alpha(2) (IC(50) 17-36 microM) but not dopamine receptors (IC(50) 0.9-2.5 mM). l-DOPA, 3-O methyldopa and DOPAC had no observable effect on binding to any of the receptors tested. These data suggest that the effects of l-DOPA in Parkinson's disease may result from actions of its metabolites dopamine and 3-MT on both dopaminergic and non-dopaminergic receptors. These findings may provide explanations for the differences between l-DOPA and dopamine receptor agonists in mediating anti parkinsonian effects and propensity to be associated with dyskinesia and motor complications such as wearing-off and on-off. PMID- 20302893 TI - Orosensory deprivation alters taste-elicited c-Fos expression in the parabrachial nucleus of neonatal rats. AB - In the present study we examined the effects of neonatal orosensory deprivation on taste-elicited gustatory activity in the rat parabrachial nucleus (PBN) using the functional anatomical marker c-Fos. Animals in three groups (GG, GO and GM) received gastric cannula implantation surgery on postnatal day 9 (P9). Animals in the fourth group (MR) did not receive any surgery. GG rats were fed by infusion of artificial milk directly into the stomach. GO rats were fed by intraoral infusion of artificial milk. GM and MR rats were reared by their mother with free access to mother's milk, water and rat chow. Rats from all groups were similar in body weight and length by P21. On P21 rats in all groups were intraorally presented with 0.5M sucrose solution and the brains were extracted and processed for c-Fos immunohistochemistry. Taste-elicited c-Fos expression in both the gustatory waist area, and the external lateral subnucleus of the PBN in rats in the GG group was significantly more robust than in the other three groups. These findings suggest a substantial alteration in orosensory-evoked neuronal response in this nucleus, due to sensory or motor deprivation during a critical developmental stage. PMID- 20302894 TI - Ca(2+)-dependent activator protein for secretion 2 and autistic-like phenotypes. AB - Ca(2+)-dependent activator protein for secretion 2 (CAPS2 or CADPS2) regulates dense-core vesicle (DCV) exocytosis. We found that CAPS2 is involved in the secretion of brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3) and that CAPS2 KO mice not only have deficits in neuronal development and survival but also exhibit abnormal behaviors, including impaired social interaction, hyperactivity, an abnormal sleep-wake rhythm and increased anxiety in unfamiliar environments. Moreover, we identified increased expression of a rare CAPS2 splice variant in autism patients that specifically lacks exon 3 and that is not transported to axons when exogenously expressed in mouse cortical neurons. Moreover, non-synonymous SNPs have been identified in some autistic patients. These results implicate CAPS2 in autism susceptibility. Therefore, CAPS2 KO mice will be a useful animal model to study the aspects of the neuropathology and behavior characteristics of neurodevelopmental disorders. PMID- 20302895 TI - Purification and characterization of a viral chitinase active against plant pathogens and herbivores from transgenic tobacco. AB - The Autographa californica nucleopolyhedrovirus chitinase A (AcMNPV ChiA) is a chitinolytic enzyme with fungicidal and insecticidal properties. Its expression in transgenic plants enhances resistance against pests and fungal pathogens. We exploited tobacco for the production of a biologically active recombinant AcMNPV ChiA (rChiA), as such species is an alternative to traditional biological systems for large-scale enzyme production. The protein was purified from leaves using ammonium sulfate precipitation followed by anion exchange and gel-filtration chromatography. Transgenic plants produced an estimated 14 mg kg(-1) fresh leaf weight, which represents 0.2% of total soluble proteins. The yield of the purification was about 14% (2 mg kg(-1) fresh leaf weight). The comparison between the biochemical and kinetic properties of the rChiA with those of a commercial Serratia marcescens chitinase A indicated that the rChiA was thermostable and more resistant at basic pH, two positive features for agricultural and industrial applications. Finally, we showed that the purified rChiA enhanced the permeability of the peritrophic membrane of larvae of two Lepidoptera (Bombyx mori and Heliothis virescens) and inhibited spore germination and growth of the phytopatogenic fungus Alternaria alternata. The data indicated that tobacco represents a suitable platform for the production of rChiA, an enzyme with interesting features for future applications as "eco-friendly" control agent in agriculture. PMID- 20302896 TI - Protein A33 responsible for antibody-resistant spread of Vaccinia virus is homologous to C-type lectin-like proteins. AB - Protein A33 is a type II membrane protein present in the outer envelope of extracellular as well as cell-associated Vaccinia virus particles. A33 has been implicated in mediating cell-to-cell virus spread in an antibody-resistant manner. Here, using state-of-the-art structure prediction methods and structural modeling, we show that A33 has most likely evolved from a C-type lectin-like protein. Comparison of the three-dimensional A33 model to the X-ray structures of distant cellular homologues revealed that A33 retained the key residues required for adopting the C-type lectin-like fold. Our results provide insights into the structure and origin of protein A33. PMID- 20302897 TI - Patterns of gene expression in swine macrophages infected with classical swine fever virus detected by microarray. AB - Infection of domestic swine with highly virulent, classical swine fever virus (CSFV) strain Brescia, causes lethal disease in all infected animals. However, the molecular mechanisms involved in modulating the host cellular processes and evasion of the immune response have not been clearly established. To gain insight into, the early host response to CSFV, we analyzed the pattern of gene expression in infected swine macrophages, using custom designed swine microarrays. Macrophages, the target cell for CSFV infection, were isolated from primary cultures of peripheral blood mononuclear cells, allowing us to utilize identical uninfected macrophages at the same time points as CSFV-infected macrophages, allowing only genes induced by CSFV to be identified. First, microarray probes were optimized by screening 244,000 probes for hybridization with RNA from infected and uninfected macrophages. Probes that hybridized and passed quality control standards were used to design a 44,000 probe microarray for this study. Changes in expression levels of 79 genes (48 up- and 31 down-regulated) during the first 48h post-infection were observed. As expected many of the genes with an altered pattern of expression are involved in the development of an innate immune response. Several of these genes had differential expression in an attenuated strain NS4B.VGIv, suggesting that some of these differences are responsible for virulence. The observed gene expression profile might help to explain the immunological and pathological changes associated with infection of pigs with CSFV Brescia. PMID- 20302898 TI - Inactivation of avian influenza virus H1N1 by photocatalyst under visible light irradiation. AB - A novel photocatalyst - ILUMIO (platinum-loaded tungsten oxide) - was evaluated for its anti-influenza virus activity with the avian isolate A/northern pintail/Miyagi/1472/08 (H1N1). Under a fluorescent lamp of 1000lx in the absence of ultraviolet light, the virus was inactivated to below the detection limit i.e. >5.3log inactivation within 2h. This photocatalyst can be used for coating walls, tables, and other surfaces to decrease virus infectivity associated with surfaces. This would be desirable to reduce transmission of infection due to indirect contact, because self-inoculation of the nasal mucosa by contaminated hands is a major transmission mode of influenza viruses from human to human, alongside with transmissions via aerosols and droplets. PMID- 20302899 TI - Efficient delivery of VEGF via heparin-functionalized nanoparticle-fibrin complex. PMID- 20302900 TI - Glial cells as sources and targets of natriuretic peptides. AB - Natriuretic peptides and their receptors are widely expressed in mammalian CNS and increasing evidence implicates them in the regulation of neural development, synaptic transmission and processing of information, and neuroprotection. Although the peptides have been mainly localized in neuronal populations they are also produced in glial cells. Astroglia and microglia also express functional natriuretic peptide receptors that can regulate important physiological responses. In this article we review evidence on the localization of natriuretic peptides and their receptors in astroglial and microglial cells and summarize data supporting the participation of this signalling system in neuron-glia and glia-brain blood vessel communication relevant to CNS function. PMID- 20302901 TI - Impaired MMN/P3a complex in first-episode psychosis: cognitive and psychosocial associations. AB - Mismatch negativity (MMN) is a neurophysiological indicator of the brain's ability to extract relevant information from an irrelevant background. The P3a orienting response often accompanies MMN in deviance detection paradigms. Both MMN and P3a have been described as reliable biomarkers of schizophrenia. MMN/P3a impairments are associated with deficits in verbal memory and attentional switching, reflecting dysfunctions in the temporal and frontal systems, respectively. It remains unresolved whether MMN/P3a are robust biomarkers of psychosis in first-episode patients. Thirty-four young people (18 to 30years) were assessed in this study; 17 first-episode psychosis (FEP) patients were compared to 17 healthy controls. To elicit MMN/P3a, a two-tone passive auditory oddball paradigm with 8% duration deviants was used; event-related potentials were recorded at frontal, central and temporal (mastoid) sites. Neuropsychological assessments included processing speed, attentional switching, simple attention, and verbal learning and memory. Social functioning and quality of life measures were also obtained. The FEP group showed significantly reduced MMN amplitudes compared to controls. The FEP group also showed significantly reduced P3a amplitudes at frontal and central sites compared with controls. As expected, the FEP group also showed significant deficits in attention and verbal learning/memory. Correlational analyses found strong associations between fronto central MMN/P3a peak amplitude and cognitive/psychosocial functioning. This study provides evidence of early neurobiological markers in young people with FEP. These findings suggest that MMN/P3a impairments are present at early stages of psychosis and that fundamental pre-attentive/deviance detection deficits may mark the beginning of progressive underlying changes with illness onset. Such deficits in FEP appear to have important links with higher-order cognitive and psychosocial functioning. PMID- 20302902 TI - Increased serum levels of high mobility group box 1 protein in patients with autistic disorder. AB - BACKGROUND: High mobility group box 1 (HMGB1) is a highly conserved, ubiquitous protein that functions as an activator for inducing the immune response and can be released from neurons after glutamate excitotoxicity. The objective of the present study was to measure serum levels of HMGB1 in patients with autistic disorder and to study their relationship with clinical characteristics. METHODS: We enrolled 22 adult patients with autistic disorder (mean age: 28.1+/-7.7 years) and 28 age- and gender-matched healthy controls (mean age: 28.7+/-8.1 years). Serum levels of HMGB1 were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: Compared with healthy subjects, serum levels of HMGB1 were significantly higher in patients with autistic disorder (10.8+/-2.6 ng/mL versus 5.6+/-2.5 ng/mL, respectively, P<0.001). After adjustment for potential confounders, serum HMGB1 levels were independently associated with their domain A scores in the Autism Diagnostic Interview-Revised, which reflects their impairments in social interaction. CONCLUSIONS: These results suggest that HMGB1 levels may be affected in autistic disorder. Increased HMGB1 may be a biological correlate of the impaired reciprocal social interactions in this neurodevelopmental disorder. PMID- 20302903 TI - Development of experimental HEMA-free three-step adhesive system. AB - OBJECTIVE: To evaluate the influence of Bis-EMA 30 on the resin-to-dentin microtensile bond strength (microTBS) and structural reliability of the experimental three-step etch-and-rinse adhesive systems. METHODS: Five experimental primers containing different dimethacrylate monomer concentrations (0, 10, 20, 40, 60 wt% of the Bis-EMA 30, P0.P60) added to acid monomer and solvents (ethanol/water), and a resin bond (Bis-GMA/TEGDMA, 50/50 wt%) were formulated. The adhesive system Scotchbond MultiPurpose (SBMP, 3M ESPE) was tested as commercial reference. Sixty bovine incisors were randomly separated into six groups, and their superficial coronal dentin was exposed. After acid etching and rinsing, the excess water was removed from the surface with absorbent paper. Each experimental primer was actively applied (30 s), followed by a mild air stream (10 s). The experimental adhesive resin was applied and light activated for 20 s. Resin composite restorations were incrementally built up. The restored teeth were stored in distilled water at 37 degrees C for 24 h, and then sectioned to obtain sticks with a cross-sectional area of approximately 0.5 mm(2), after which 24 specimens per group were subjected to the microTBS test. Data (MPa) were analyzed by One-way ANOVA, Tukey test (alpha=0.05) and Weibull analysis. RESULTS: The P40 group showed microTBS means similar to those of the control (SBMP), whereas both had statistically higher values when compared with the other groups (p<0.001). Moreover, P40 showed higher structural reliability, represented by the high Weibull modulus and characteristic strength values. The lowest microTBS was observed in the P0, P10 and P20 groups, which also had low structural reliability. SIGNIFICANCE: Bis-EMA 30 is a promising monomer to be considered as a substitute for HEMA in adhesive system compositions. PMID- 20302904 TI - Extrinsic energy sources affect hardness through depth during set of a glass ionomer cement. AB - OBJECTIVE: To investigate the effect of various energy sources on the upper and lower surface hardness of a setting glass ionomer with various thicknesses. METHOD: Cylindrical specimens (4 mm diameter by 1, 2 or 4 mm thickness) of a glass-ionomer cement were prepared with no applied energy source (control), by preheating GIC capsules in a waterbath prior to mixing, application of light with high irradiance or ultrasonic excitation with a scaler tip. The upper and lower surface hardness was measured 0.5 h, 4 h and 1 week following material mixing. The increase in temperature towards the lower surface of each specimen was monitored throughout the first 5 min of setting. RESULTS: No significant differences in hardness between upper and lower surfaces or varying thicknesses were identified for control and preheated samples at any post-mix time (p>0.05). At 0.5 h post-mix, the upper surface hardness of preheated, light and ultrasonic treatments was significantly increased compared with that of the control groups. Following 4 h post-mix, the overall hardness of preheated samples was significantly greater (p<0.001) than other sample groups, which were not statistically different (p=0.684). No significant differences in hardness between test groups were identified following 1 week (p>0.05). CONCLUSIONS: Preheating GIC capsules prior to mixing resulted in superior hardness values through depth up to and including 4 h post-mix compared with specimen surfaces treated with light irradiation or with an ultrasonic scaler tip. PMID- 20302905 TI - Glutathione reductase plays an anti-apoptotic role against oxidative stress in human hepatoma cells. AB - The cellular roles of glutathione reductase (GR) in the reactive oxygen species (ROS)-induced apoptosis were studied using the HepG2 cells transfected with GR. The overexpression of GR caused a marked enhancement in reduced and oxidized glutathione (GSH/GSSG) ratio, and significantly decreased ROS levels in the stable transfectants. Hydrogen peroxide (H(2)O(2)), under the optimal condition for apoptosis, significantly decreased cellular viability and total GSH content, and rather increased ROS level, apoptotic percentage and caspase-3 activity in the mock-transfected cells. However, hydrogen peroxide could not largely generate these apoptotic changes in cellular viability, ROS level, apoptotic percentage, caspase-3 activity and total GSH content in the cells overexpressing GR. Taken together, GR may play a protective role against oxidative stress. PMID- 20302906 TI - Cortisol response to the Trier Social Stress Test in obese and reduced obese individuals. AB - Impact of body weight loss, body fat distribution and the nutritional status on the cortisol response to the Trier Social Stress Test (TSST) was investigated in this study. Fifty-one men (17 non-obese, 20 abdominally obese and 14 reduced obese) and 28 women (12 non-obese, 10 peripherally obese and 6 reduced obese) were subjected to the TSST in fed and fasted states. The TSST response was determined using salivary cortisol measurements. The nutritional status (being fed or fasted) had no effect on the cortisol levels during and following the TSST. Reduced obese men exhibited lower cortisol levels than non-obese men. Cortisol levels in obese men were not different from those of non-obese and reduced obese subjects. In women, there was no significant difference between groups. These finding suggest that weight status in men influences cortisol reactivity to a psychological stress and the different responses seen among genders could be linked to the different fat distributions that characterize men and women. PMID- 20302907 TI - Hodgkin-Huxley type modelling and parameter estimation of GnRH neurons. AB - In this paper a simple one compartment Hodgkin-Huxley type electrophysiological model of GnRH neurons is presented, that is able to reasonably reproduce the most important qualitative features of the firing pattern, such as baseline potential, depolarization amplitudes, sub-baseline hyperpolarization phenomenon and average firing frequency in response to excitatory current. In addition, the same model provides an acceptable numerical fit of voltage clamp (VC) measurement results. The parameters of the model have been estimated using averaged VC traces, and characteristic values of measured current clamp traces originating from GnRH neurons in hypothalamic slices. The resulting parameter values show a good agreement with literature data in most of the cases. Applying parametric changes, which lead to the increase of baseline potential and enhance cell excitability, the model becomes capable of bursting. The effects of various parameters to burst length have been analyzed by simulation. PMID- 20302908 TI - 6 Iodo-delta-lactone reproduces many but not all the effects of iodide. AB - BACKGROUND: Iodide has direct effects on thyroid function. Several iodinated lipids are biosynthesized by the thyroid and they were postulated as intermediaries in the action of iodide. Among them 6 iodo-delta-lactone (IL delta) has been identified and proposed to play a role in thyroid autoregulation. The aim of this study was to compare the effect of iodide and IL-delta on several thyroid parameters. METHODS: Thyroid bovine follicles were incubated with the different compounds during three days. RESULTS: KI and IL-delta inhibited iodide uptake, total protein and Tg synthesis but only KI had an effect on NIS and Tg mRNAs levels. Both compounds inhibited Na+/K+ ATPase and deoxy-glucose uptake. As PAX 8, FOXE 1 and TITF1 are involved in the regulation of thyroid specific genes their mRNA levels were measured. While iodide inhibited the expression of the first two, the expression of TITF1 was stimulated by iodide and IL-delta had no effect on these parameters. CONCLUSION: These findings indicate that IL-delta reproduces some but not all the effects of excess iodide. These observations apply for higher micromolar concentrations of iodide while no such effects could be demonstrated at nanomolar iodide concentrations. PMID- 20302910 TI - Genetics and phenomics of hypothyroidism and thyroid dys- and agenesis due to PAX8 and TTF1 mutations. AB - Thyroid dysgenesis (TD) is the most common cause of congenital hypothyroidism (CH), a relatively frequent endocrine disease in newborns (1 in 3000-4000 live births). TD is a defect in the organogenesis of the gland resulting in hypoplastic, ectopic or absent-thyroid gland. TD is usually sporadic but mutations in transcription factors (PAX8, TTF1, FOXE1 and NKX2-5) involved in thyroid development have been shown to cause a minority of cases transmitted as Mendelian diseases. This review focuses on the genetics and phenomics of hypothyroidism and TD due to PAX8 and TTF1 mutations. PMID- 20302909 TI - Estrogen receptor alpha 46 is reduced in tamoxifen resistant breast cancer cells and re-expression inhibits cell proliferation and estrogen receptor alpha 66 regulated target gene transcription. AB - Resistance to endocrine therapy is a major clinical problem in breast cancer. The role of ERalpha splice variants in endocrine resistance is largely unknown. We observed reduced protein expression of an N-terminally truncated ERalpha46 in endocrine-resistant LCC2, LCC9, and LY2 compared to MCF-7 breast cancer cells. Transfection of LCC9 and LY2 cells with hERalpha46 partially restored growth inhibition by TAM. Overexpression of hERalpha46 in MCF-7 cells reduced estradiol (E(2))-stimulated endogenous pS2, cyclin D1, nuclear respiratory factor-1 (NRF 1), and progesterone receptor transcription. Expression of oncomiR miR-21 was lower in TAM-resistant LCC9 and LY2 cells compared to MCF-7 cells. Transfection with ERalpha46 altered the pharmacology of E(2) regulation of miR-21 expression from inhibition to stimulation, consistent with the hypothesis that hERalpha46 inhibits ERalpha activity. Established miR-21 targets PTEN and PDCD4 were reduced in ERalpha46-transfected, E(2)-treated MCF-7 cells. In conclusion, ERalpha46 appears to enhance endocrine responses by inhibiting selected ERalpha66 responses. PMID- 20302911 TI - Auditory-evoked masseter inhibitory reflex. AB - We aimed to investigate auditory-evoked masseter inhibitory reflex and discuss possible auditory-trigeminal pathways in brainstem. Our study population consisted of 21 healthy volunteers (age-matched 7 males and 14 females). Bilateral electrical blink reflex (BR), auditory blink reflexes (ABR) and electrical MIR (MIR) were studied. After obtaining normal potentials, auditory MIR (AMIR) was studied. Electrical blink reflexes had two components as R1 and R2, and ABR had one evoked potential in all volunteers. There was no significant difference between gender, nor between right- and left-sided BR and ABR. The mean latency of ABR responses were shorter than latencies of R2 phase of BR (p=0.013 for left-sided responses, p=0.035 for right-sided responses). Electrical stimulation revealed two suppression periods (SP1 and SP2) in MIR responses bilaterally in all volunteers. Auditory stimulation evoked typical two suppression periods only in 11 subjects (5 males, 6 females). The mean latency of SP1 component of AMIR was significantly longer than those of MIR bilaterally in both males and females, while the SP2 component had a shorter onset. The durations of SP1, SP2 and total SP were always shorter than those obtained in MIR with smaller degree of suppressions. None of the MIR or AMIR responses showed significance difference between sexes. We assume that auditory-evoked MIR might share the similar interneurons as with other electrical or nociceptive stimulation, which connects cochlear-trigeminal neurons via pontine reticular system to premotor area for masseter muscle. PMID- 20302912 TI - Combining spatial and temporal information to explore resting-state networks changes in abstinent heroin-dependent individuals. AB - Majority of previous heroin fMRI studies focused on abnormal brain function in heroin-dependent individuals. However, few fMRI studies focused on the resting state abnormalities in heroin-dependent individuals and assessed the relationship between the resting-state functional connectivity changes and duration of heroin use. In the present study, discrete cosine transform (DCT) was employed to explore spatial distribution of low frequency BOLD oscillations in heroin dependent individuals and healthy subjects during resting-state; meanwhile resting-state functional connectivity analysis was used to investigate the temporal signatures of overlapping brain regions obtained in DCT analysis among these two groups. Main finding of the present study is that the default mode network (DMN) and rostral anterior cingulate cortex (rACC) network of heroin dependent individuals were changed compared with healthy subjects. More importantly, these changes negatively correlated with duration of heroin use. These resting-state functional abnormalities in heroin-dependent individuals provided evidence for abnormal functional organization in heroin-dependent individuals, such as functional impairments in decision-making and inhibitory control. PMID- 20302913 TI - Individual differences in cocaine-induced locomotor activity of male Sprague Dawley rats are not explained by plasma corticosterone levels. AB - Humans differ in their initial response to, and subsequent abuse of, addictive drugs like cocaine. Rodents also exhibit marked individual differences in responsiveness to cocaine. Previously, we classified male Sprague-Dawley rats as either low or high cocaine responders (LCRs or HCRs, respectively), based on their acute low-dose cocaine-induced locomotor activity, and found that with repeated drug exposure LCRs exhibit greater cocaine locomotor sensitization, reward and reinforcement than HCRs. Differential cocaine-induced increases in striatal dopamine help to explain the LCR/HCR phenotypes. Differential levels of stress and/or anxiety could also contribute but have not been explored. Here we measured open-field activity and plasma corticosterone levels both pre- and post cocaine treatment in LCRs, HCRs, and saline-treated controls. The three groups did not differ in baseline locomotor activity or corticosterone levels. Importantly, LCR/HCR differences in corticosterone levels were also not observed following acute cocaine (10mg/kg, i.p.), when cocaine induced approximately 3.5 fold greater locomotor activity in HCRs than LCRs. Additionally, there were no LCR/HCR differences in plasma corticosterone levels following 5 days of once daily cocaine, during which time LCRs developed locomotor sensitization such that their cocaine-induced locomotor activity no longer differed from that of HCRs. Likewise, there were no group activity differences in any of four concentric zones within the open-field chamber. In summary, neither plasma corticosterone levels nor thigmotaxis-type anxiety appears to be a factor that contributes to the observed cocaine-induced LCR/HCR behavioral differences. PMID- 20302914 TI - Functional connectivity in fronto-subcortical circuitry during the resting state in obsessive-compulsive disorder. AB - Obsessions and compulsions mediated by cognitive inflexibility might be associated with abnormal resting state functional connectivity in the default mode network (DMN) that represents intrinsically generated neuronal activity. It was hypothesized that decreased functional connectivity in the DMN would occur in components of fronto-subcortical circuits in patients with obsessive-compulsive disorder (OCD). Twenty-two unmedicated OCD patients and 22 age- and sex-matched healthy controls received resting state functional scanning runs. The posterior cingulate cortex (PCC) region was chosen as the seed region for the connectivity analysis. Correlations between temporal connectivity with the seed region and scores on clinical measures and obsessive-compulsive symptom dimensions were also assessed. OCD patients demonstrated less functional connectivity within the DMN in the anterior cingulate cortex, middle frontal gyrus, and putamen compared to controls. The functional connectivity to the PCC seed region in OCD patients was in the direction opposite to that in the prefrontal areas with regard to scores on cleaning and obsessions/checking dimensions of OCD. These data provide evidence for fronto-subcortical dysfunction in OCD. Results from this study also support the notion that OCD is a heterogeneous disorder mediated by distinct circuits. PMID- 20302915 TI - Assessing the role of the medial preoptic area in ethanol-induced hypothermia. AB - Administration of ethanol produces hypothermia. The preoptic area/anterior hypothalamus (POA/AH) contains warm- and cold-sensitive neurons that are important for temperature regulation. The present study evaluated the effect of ethanol on Fos immunoreactivity (Fos-ir) in the medial preoptic area (MPOA) and the effect of lesions to the MPOA on ethanol-induced hypothermia. Rats receiving 1.5-g/kg ethanol showed an increase in Fos-ir in the MPOA. However, lesions to the MPOA did not affect core body temperature. These findings indicate that ethanol increases neural activity in the MPOA, but this increased activity does not influence ethanol-induced changes in core body temperature. PMID- 20302916 TI - The potential role of ubiquitin c-terminal hydrolases in oncogenesis. AB - Deubiquitinating enzymes (DUBs), capable of removing ubiquitin (Ub) from protein substrates, are involved in numerous biological processes. The ubiquitin C terminal hydrolases (UCHs) subfamily of DUBs consists of four members: UCH-L1, UCH-L3, UCH37 and BRCA1-associated protein-1 (BAP1). UCH-L1 possesses deubiquitinating activity and dimerization-dependent ubiquitin ligase activity, and functions as a mono-ubiquitin stabilizer; UCH-L3 does both deubiquitinating and deneddylating activity, except dimerization or ligase activity, and unlike UCH-L1, can interact with Lys48-linked Ub dimers to protect it from degradation and in the meanwhile to inhibit its hydrolase activity; UCH37 is responsible for the deubiquitinating activity in the 19S proteasome regulatory complex, and as indicated by the recent study, UCH37 is also associated with the human Ino80 chromatin-remodeling complex (hINO80) in the nucleus and can be activated via transient association of 19S regulatory particle- or proteasome-bound hRpn13 with hINO80; BAP1, binding to the wild-type BRCA1 RING finger domain, is regarded as a tumor suppressor, but for such suppressing activity, as demonstrated otherwise, both deubiquitinating activity and nucleus localization are required. There is growing evidence that UCH enzymes and human malignancies are closely correlated. Previous studies have shown that UCH enzymes play a crucial role in some signalings and cell-cycle regulation. In this review, we provided an insight into the relation between UCH enzymes and oncogenesis. PMID- 20302917 TI - Bursts and hyperexcitability in non-myelinated axons of the rat hippocampus. AB - Strict control over the initiation of action potentials is the primary task of a neuron. One way to lose proper spike control is to create several spikes, a burst, when only one should be initiated. We describe a new site for burst initiation in rat hippocampal CA3 neurons: the Schaffer collateral axons. These axons lack myelin, are long, extremely thin, and form synapses along their entire paths, features typical for many, if not most cortical axons in the mammalian brain. We used hippocampal slices and recorded from individual Schaffer collateral axons. We found that single action potentials were converted into bursts of two to six action potentials after blocking 4-aminopyridine (4-AP) sensitive K(+) channels. The CA3 somata and initial part of their axons were surgically removed in these experiments, leading to the conclusion that the bursts were initiated far out in the axons. This conclusion was supported by two additional kinds of experiments. First, local application of 4-AP to one out of two stimulated axonal branches of the same neuron showed bursting only at the 4 AP exposed branch. Second, intracellular recordings from CA3 somata showed that some spontaneously occurring bursts were resistant to somatic hyperpolarization. We then investigated a hyperexcitable period that follows individual spikes in the Schaffer collaterals. With extracellular excitability testing, we showed that the time course of this hyperexcitability was compatible with that of the bursts, so this hyperexcitability could be the underlying cause of the bursts. Furthermore, the hyperexcitability was enhanced by low doses of 4-AP (20 microM), alpha-dendrotoxin (alpha-DTX) or margatoxin (MgTX). Kv1.2 containing channels may therefore dampen the hyperexcitability, but because bursting was observed only at high 4-AP concentration (1 mM), other channels may be needed to prevent axonal bursting. PMID- 20302919 TI - Acetyl-L-carnitine increases artemin level and prevents neurotrophic factor alterations during neuropathy. AB - Damages to the nervous system are the primarily cause of neuropathy and chronic pain. Current pharmacological treatments for neuropathic pain are not able to prevent or revert morphological and molecular consequences of tissue injury. On the other hand, many neurotrophins, like nerve growth factor (NGF), paired off restorative effects with hyperalgesia. Interestingly, the glial cell line-derived neurotrophic factors GDNF and Artemin (ARTN) seem to support neuron survival and to normalize abnormal pain behaviour. In the present research protein levels of NGF, GDNF and ARTN were evaluated in a rat model of peripheral neuropathy, the chronic constriction injury (CCI). NGF was increased by CCI in the ipsilateral dorsal root ganglia (DRG), in the spinal cord and in the periaqueductal grey matter (PAG). On the contrary, ARTN was decreased bilaterally in DRG, spinal cord and PAG. GDNF levels decreased in ipsilateral DRG, whereas the constriction did not modify its expression in the central nervous system districts. Repeated treatments with the antihyperalgesic and neuroregenerative compound acetyl-l carnitine (ALCAR; 100 mgkg(-1) i.p. twice daily for 15 days) was able to prevent the increase of NGF levels. In conditions of pain relief ALCAR normalized peripheral and central alterations of GDNF and ARTN levels. Characteristically, sham animals that underwent the same ALCAR treatment, showed increased levels of ARTN both in the DRG and in the spinal cord. These data offer a new point of view on the mechanism of the antihyperalgesic as well as the neuroprotective effect of ALCAR. PMID- 20302918 TI - Effects of age on axon terminals forming axosomatic and axodendritic inhibitory synapses in prefrontal cortex. AB - Much of the cognitive decline shown by aging primates can be attributed to dysfunction of prefrontal cortex and, as shown previously, about 30% of asymmetric (excitatory) and symmetric (inhibitory) axodendritic synapses are lost from the neuropil of layer 2/3 in prefrontal area 46 with age [Peters A, Sethares C, Luebke JI (2008) Neuroscience 152:970-981]. Whether there is a similar loss of inhibitory axosomatic synapses from this cortex has not been determined, but a study in primate motor cortex suggests that axosomatic synapses are not lost with age [Tigges J, Herndon JG, Peters A (1992) Anat Rec 232:305-315]. The present study is focused upon whether the remaining axon terminals forming inhibitory synapses in old monkeys hypertrophy to compensate for any age-related loss. Analysis of electron micrographs show that in layer 2/3 of area 46 in both young and old monkeys, axon terminals forming axosomatic synapses are significantly larger and contain more mitochondria than those forming axodendritic synapses and both axodendritic and axosomatic terminals become larger with age. However, while mitochondria in axodendritic terminals do not change in either size or amount with age, the mitochondria in axosomatic terminals become larger. Similarly, in terminals forming axodendritic synapses, the mean numbers of synaptic vesicle profiles is the same in young and old monkeys, whereas in terminals forming axosomatic synapses there is an increase in the numbers of synaptic vesicles with age. We also show that among these age-related changes, only the numbers of synaptic vesicles in axosomatic synapses are significantly correlated with the cognitive impairment indices displayed by the same monkeys. In summary, the data provide original evidence that axosomatic axon terminals increase in size and in their content of mitochondria and synaptic vesicles. Furthermore, based on our and previously published results, we speculate that these changes are linked to age-related cognitive decline. PMID- 20302920 TI - The essential oil of Eucalyptus tereticornis, and its constituents alpha- and beta-pinene, potentiate acetylcholine-induced contractions in isolated rat trachea. AB - The effects of the essential oil of Eucalyptus tereticornis (EOET), especially the effects of its constituents alpha- and beta-pinene, were studied on rat trachea in vitro. In tracheal rings, EOET, alpha- or beta-pinene potentiated the contractions induced by acetylcholine (ACh). Contractions induced by K(+) (60mM) were also potentiated by alpha- and beta-pinene, but were reduced by EOET. Our findings show that EOET has myorelaxant effects on rat airways, but potentiates ACh-induced contractions. Monoterpenes alpha- and beta-pinene are involved in its potentiating actions, but are not responsible for its myorelaxant effects. A putative inhibition of the acetylcholinesterase enzyme is involved. PMID- 20302921 TI - Chemical constituents of the Vietnamese liverwort Porella densifolia. AB - From the ether extract of Porella densifolia, the first liverwort collected and chemically investigated in Vietnam, a kaurane diterpenoid, ent-kauren-15-one (1) and two sesquiterpene norpinguisone (2) and norpinguisone methyl ester (3) have been purified. Their structures were elucidated by spectroscopic analysis. In addition, an X-ray crystal structure of norpinguisone was obtained, allowing to determine its stereochemistry. Furthermore, the inhibitory activity of nitric oxide (NO) production in RAW 264.7 cells stimulated by lipopolysaccharide (LPS) of compounds 1-3 was examined with their IC(50) values of 69.4, 45.5 and 1.68 microM, respectively. PMID- 20302922 TI - A new 7-oxygenated coumarin from Clausena suffruticosa. AB - A new coumarin, 7-[(2'E,6'E)-7'-carboxy-5'(zeta)-hydroxy-3'-methylocta-2',6' dienyloxy]-coumarin, was isolated from the leaf of Clausena suffruticosa. Its structure was established by means of spectroscopic data analyses, including mass spectrometry and both 1D and 2D NMR spectroscopy. PMID- 20302923 TI - Chitin disaccharide (GlcNAc)2 induces natural competence in Vibrio cholerae through transcriptional and translational activation of a positive regulatory gene tfoXVC. AB - A pathogenic marine bacterium Vibrio cholerae shows natural competence for genetic transformation in the presence of chitin, a polymer of N acetylglucosamine (GlcNAc). In this study, we extensively analyzed the regulatory mechanisms of tfoX(VC), encoding an activator protein for the chitin-induced competence. Using a chromosomal tfoX(VC)-lacZ reporter system, we showed that a disaccharide of chitin, (GlcNAc)(2), at least was needed to activate both the transcription and translation of tfoX(VC). This activation was moderate at the transcriptional level but was strong at the translational level. We also identified two sequence elements, one for transcription and another for translation. The transcriptional control element (TCE) included a 34-bp potential transcriptional operator overlapped by the tfoX(VC) promoter, while the translational control element (TLE) consisted of a 42-bp sequence located within the 5'-untranslated region. Deletion of either TCE or TLE still resulted in (GlcNAc)(2)-dependent competence for exogenous DNA. However, the deletion in both elements induced competence for transformation at high efficiency regardless of the presence or absence of (GlcNAc)(2). These results suggested the dual activation of tfoX(VC) expression to be essential to induce competence. The highly transformable strain created here should aid the study of natural competence in V. cholerae. PMID- 20302924 TI - Preliminary assessment of COSII gene diversity in lulo and a relative species: initial identification of genes potentially associated with domestication. AB - Among the Solanum genus, Solanum quitoense Lam. (lulo) is a promising species of Neotropical Solanaceae to become a premium crop in international markets. Wild relatives of S. quitoense are a source of desirable characteristics to be exploited for genetic improvement. To enhance the understanding of and access to the genetic diversity in landrace and wild relatives of lulo, we estimated the relative sequence diversity among them and their wild relative Solanum hirtum. With the use of COSII markers, we established that diversity of cultivated lulo (S. quitoense) is significantly lower than that of its wild relative S. hirtum. In the same way, we found that diversity of lulo is similar to that previously reported for tomato, while the diversity of S. hirtum is comparable to that of other wild relatives of cultivated plants. Our results suggest that high variability of some genes associated to abiotic stress response and pathogen resistance has been favored in wild and cultivated lulo plants. PMID- 20302925 TI - The advantages of a novel CoQ10 delivery system in skin photo-protection. AB - Skin photo-ageing induced by ultraviolet (UV) radiation is mainly ascribed to oxidative stress and reactive oxygen species (ROS). Coenzyme Q10 (CoQ10) has been reported as a powerful antioxidant in plasma. However, CoQ10 was barely satisfactory in topical drug delivery because of its lipid solubility. To improve the anti-oxidative efficiency of CoQ10 in skin photo-ageing, the present research prepared a novel CoQ10 nano-structured lipid carrier (CoQ10-NLC) and characterised it by size and freeze-fracture transmission electron microscopy (FF TEM). In UVA-irradiated fibroblasts, the protection of CoQ10-NLC was more effective than the CoQ10-emulsion as demonstrated by cell viability and morphological changes of the cell body and nucleus. In addition, malondialdehyde (MDA, the product of lipid peroxidation) concentration decreased by 61.5% in the group treated with CoQ10-NLC compared to the group subjected to general CoQ10 emulsion. In the presence of CoQ10-NLC, the activities of the anti-oxidative enzymes superoxide dismutase (SOD) and glutathione peroxidase (GSH-px) were reinstated to 81% and 75%, respectively, of the control group. In vivo, the CoQ10 NLC displayed a stronger capability to penetrate the stratum corneum and permeate the dermis after a topical skin application. These results reveal that CoQ10-NLC has greater antioxidant properties and topical skin penetration than the CoQ10 emulsion. PMID- 20302926 TI - Preparation and cytotoxic activity of hydroxycamptothecin nanosuspensions. AB - Hydroxycamptothecin is a promising anticancer agent that possesses the ability to inhibit the growth of a wide range of human tumors. Owing to its poor solubility and instability, the pharmaceutical development and clinical utilization of hydroxycamptothecin have been limited. In the present study, a novel precipitation-combined high-pressure homogenization (PCH) technique was used to prepare hydroxycamptothecin nanosuspensions. Based on the homogenization pressure and number of cycles, the process with 10 cycles at 18,000 psi of homogenization pressure was found to be the most efficient method to achieve consistent particle size reduction. It was used to prepare nanosuspensions for characterization and evaluation of the formulation performance. Lyophilization of hydroxycamptothecin nanosuspensions, the shape and crystal form of the drug, and antiproliferative activity were also studied. The mean particle size (z-ave) of the reconstituted freeze-dried powder was small and uniform. The freeze-dried powder might be a good choice for intravenously administrating poorly soluble hydroxycamptothecin, which proved to have higher cytotoxicity against the cancer cells than hydroxycamptothecin injections (p<0.001). Overall, these studies have demonstrated that the PCH technique can be used successfully to prepare hydroxycamptothecin nanosuspensions. PMID- 20302928 TI - Importance of lactobacilli in food and feed biotechnology. AB - The genus Lactobacillus is a heterogeneous group of lactic acid bacteria (LAB) with important implications in food fermentation. The ability to colonize a variety of habitats is a direct consequence of the wide metabolic versatility of this group of LAB. Consequently, lactobacilli have been used for decades in food preservation, as starters for dairy products, fermented vegetables, fish and sausages as well as silage inoculants. Lactobacilli have also been proposed as probiotics and microbial cell factories for the production of nutraceuticals. However, a wide range of applications of lactobacilli in food biotechnology remains potential, whereas a number of important strains still need to be discovered and characterized. This article provides an overview of the taxonomy of lactobacilli and describes four of the most significant case studies on the application of this group of LAB in food and feed biotechnology, including their use as probiotics, dairy starters, silage inoculants, and microbial cell factories. The importance of access to and exchange of biological material within and between different strain collections as a crucial step in expanding the range of different biotechnological applications of lactobacilli is also emphasized. PMID- 20302927 TI - Oxidative stress modulates PPAR gamma in vascular endothelial cells. AB - The peroxisome proliferator-activated receptor gamma (PPAR gamma) plays an important role in vascular regulation. However, the impact of oxidative stress on PPAR gamma expression and activity has not been clearly defined. Human umbilical vein endothelial cells (HUVECs) were exposed to graded concentrations of H(2)O(2) for 0.5-72h, or bovine aortic endothelial cells (BAECs) were exposed to alterations in extracellular thiol/disulfide redox potential (E(h)) of the cysteine/cystine couple. Within 2h, H(2)O(2) reduced HUVEC PPAR gamma mRNA and activity and reduced the expression of two PPAR gamma-regulated genes without altering PPAR gamma protein levels. After 4h H(2)O(2) exposure, mRNA levels remained reduced, whereas PPAR gamma activity returned to control levels. PPAR gamma mRNA levels remained depressed for up to 72 h after exposure to H(2)O(2), without any change in PPAR gamma activity. Catalase prevented H(2)O(2)-induced reductions in PPAR gamma mRNA and activity. H(2)O(2) (1) reduced luciferase expression in HUVECs transiently transfected with a human PPAR gamma promoter reporter, (2) failed to alter PPAR gamma mRNA half-life, and (3) transiently increased expression and activity of c-Fos and phospho-c-Jun. Treatment with the AP1 inhibitor curcumin prevented H(2)O(2)-mediated reductions in PPAR gamma expression. In addition, medium having an oxidized E(h) reduced BAEC PPAR gamma mRNA and activity. These findings demonstrate that oxidative stress, potentially through activation of inhibitory redox-regulated transcription factors, attenuates PPAR gamma expression and activity in vascular endothelial cells through suppression of PPAR gamma transcription. PMID- 20302929 TI - Glutaric aciduria type I and methylmalonic aciduria: simulation of cerebral import and export of accumulating neurotoxic dicarboxylic acids in in vitro models of the blood-brain barrier and the choroid plexus. AB - Intracerebral accumulation of neurotoxic dicarboxylic acids (DCAs) plays an important pathophysiological role in glutaric aciduria type I and methylmalonic aciduria. Therefore, we investigated the transport characteristics of accumulating DCAs - glutaric (GA), 3-hydroxyglutaric (3-OH-GA) and methylmalonic acid (MMA) - across porcine brain capillary endothelial cells (pBCEC) and human choroid plexus epithelial cells (hCPEC) representing in vitro models of the blood brain barrier (BBB) and the choroid plexus respectively. We identified expression of organic acid transporters 1 (OAT1) and 3 (OAT3) in pBCEC on mRNA and protein level. For DCAs tested, transport from the basolateral to the apical site (i.e. efflux) was higher than influx. Efflux transport of GA, 3-OH-GA, and MMA across pBCEC was Na(+)-dependent, ATP-independent, and was inhibited by the OAT substrates para-aminohippuric acid (PAH), estrone sulfate, and taurocholate, and the OAT inhibitor probenecid. Members of the ATP-binding cassette transporter family or the organic anion transporting polypeptide family, namely MRP2, P-gp, BCRP, and OATP1B3, did not mediate transport of GA, 3-OH-GA or MMA confirming the specificity of efflux transport via OATs. In hCPEC, cellular import of GA was dependent on Na(+)-gradient, inhibited by NaCN, and unaffected by probenecid suggesting a Na(+)-dependent DCA transporter. Specific transport of GA across hCPEC, however, was not found. In conclusion, our results indicate a low but specific efflux transport for GA, 3-OH-GA, and MMA across pBCEC, an in vitro model of the BBB, via OAT1 and OAT3 but not across hCPEC, an in vitro model of the choroid plexus. PMID- 20302930 TI - Menage a trois: aldosterone, sodium and nitric oxide in vascular endothelium. AB - Aldosterone, a mineralocorticoid hormone mainly synthesized in the adrenal cortex, has been recognized to be a regulator of cell mechanics. Recent data from a number of laboratories implicate that, besides kidney, the cardiovascular system is an important target for aldosterone. In the endothelium, it promotes the expression of epithelial sodium channels (ENaC) and modifies the morphology of cells in terms of mechanical stiffness, surface area and volume. Additionally, it renders the cells highly sensitive to small changes in extracellular sodium and potassium. In this context, the time course of aldosterone action is pivotal. In the fast (seconds to minutes), non-genomic signalling pathway vascular endothelial cells respond to aldosterone with transient swelling, softening and insertion of ENaC in the apical plasma membrane. In parallel, nitric oxide (NO) is released from the cells. In the long-term (hours), aldosterone has opposite effects: The mechanical stiffness increases, the cells shrink and NO production decreases. This leads to the conclusion that both the physiology and pathophysiology of aldosterone action in the vascular endothelium are closely related. Aldosterone, at concentrations in the physiological range and over limited time periods can stabilize blood pressure and regulate tissue perfusion while chronically high concentrations of this hormone over extended time periods impair sodium homeostasis promoting endothelial dysfunction and the development of tissue fibrosis. PMID- 20302931 TI - Vitamin D as an inducer of cathelicidin antimicrobial peptide expression: past, present and future. AB - Vitamin D was discovered as the preventive agent of nutritional rickets, a defect in bone development due to inadequate uptake of dietary calcium. However, a variety of studies over the last several years has revealed that vitamin D controls much more than calcium homeostasis. For example, recent research has underlined the key role of vitamin D signaling in regulation of innate immunity in humans. Vitamin D is converted to 25-hydroxyvitamin D (25D), its major circulating form, and then to hormonal 1,25-dihydroxyvitamin D (1,25D) in target cells. We now know that when cells of the immune system such a macrophages sense a bacterial infection they acquire the capacity to convert circulating 25D into 1,25D. Moreover, 1,25D thus produced is a direct inducer of expression of genes encoding antimicrobial peptides, in particular cathelicidin antimicrobial peptide (CAMP). Antimicrobial peptides such as CAMP are vanguards of innate immune responses to bacterial infection and can act as signaling molecules to regulate immune system function. This review covers what we have learned in the past few years about the expression and function of CAMP under physiological and pathophysiological conditions, and addresses the potential future applications of vitamin D analogues to therapeutic regulation of CAMP expression. PMID- 20302932 TI - Human T lymphocytes are direct targets of 1,25-dihydroxyvitamin D3 in the immune system. AB - Besides its actions on minerals and bone, the bioactive vitamin D metabolite, 1,25-dihydroxyvitamin D3 (1,25(OH)2D3), has important immunomodulatory properties. Within the immune system, dendritic cells represent key targets for this hormone and 1,25(OH)2D3-induced changes in their phenotype and function ultimately affects T lymphocytes. However, the presence of vitamin D receptors (VDR) in activated T cells proposes additional mechanisms for 1,25(OH)2D3 to directly regulate T cell responses. Here, we investigated the expression and kinetics of vitamin D-related genes in human activated T lymphocytes. Different activation stimuli elicited increased VDR- and 1-alpha-hydroxylase expression, with a highly similar kinetic pattern. Addition of 1,25(OH)2D3 effectively triggered VDR signaling, as evidenced by 24-hydroxylase induction, but only when introduced to T lymphocytes expressing high levels of VDR. This enhanced degree of VDR signaling correlated with a stronger inhibition of cytokines (IFN-gamma, IL-10) and modulation of homing receptor expression (CCR10, CLA) in long-term T cell cultures. Importantly, chronic 1,25(OH)2D3-exposure further amplified VDR signaling and the concomitant T cell modulating effects. In conclusion, we validate T cells as direct targets for 1,25(OH)2D3 and provide this optimized in vitro model to improve our understanding of the role of vitamin D as a direct regulator of T cell responses. PMID- 20302934 TI - A new marker for early diagnosis of 21-hydroxylase deficiency: 3beta,16alpha,17alpha-trihydroxy-5alpha-pregnane-7,20-dione. AB - In neonates with 21-hydroxylase deficiency the specific marker 11-oxo pregnanetriol is at low levels in the first days of life and this drives the search for alternatives. We describe the structural characterisation of a new early marker, 3beta,16alpha,17alpha-trihydroxy-5alpha-pregnane-7,20-dione. Urine samples from 87 untreated and 11 recently treated newborns with 21-hydroxylase deficiency (42 males and 56 females) between birth and 40 days of age and control samples from 7 healthy neonates (4 males, 3 females) were compared. Steroids were analyzed as methyloxime-trimethylsilyl ether derivatives by GC-MS and GC-MS/MS, after extraction and enzymatic conjugate hydrolysis. Microchemical methods and deuterated derivatives were used. The new steroid was identified by comparison with 3beta,16alpha,17alpha-trihydroxy-preg-5-en-20-one and 3beta-hydroxy-5alpha pregnane-7,20-dione standards. It was present for the first 4 weeks after birth (with a maximum around day 4) and showed a marked inter-individual variability. No effect of treatment was evident and levels were much higher than for 11-oxo pregnanetriol in the first days of life. Only traces were found in controls. The likely involvement of oxysterol 7alpha-hydroxylase (CYP7B1) from the 'acidic' pathway of bile acid synthesis and 11beta-hydroxysteroid dehydrogenase-1 in the generation of the 7-oxo group is discussed. We conclude that this steroid is a useful early marker of 21-hydroxylase deficiency. PMID- 20302933 TI - Seasonal 25-hydroxyvitamin D changes in British postmenopausal women at 57 degrees N and 51 degrees N: a longitudinal study. AB - The UK has insufficient intensity of sunlight at wavelengths 290-315 nm to enable cutaneous synthesis of vitamin D from October to April. There are regional differences in UVB strength throughout the UK but whether this translates to differences in vitamin D status is not known. We have reported seasonal variations in a cross-sectional study of over 3000 Scottish women in Aberdeen. The aim of this longitudinal study was to compare the seasonal variation of serum 25-hydroxyvitamin D [25(OH)D] in postmenopausal women residing in Aberdeen (57 degrees N) and Surrey (51 degrees N). Women attended 3-monthly visits over 12 months, starting summer 2006. In Aberdeen, 338 Caucasian women (mean age+/-SD, 61.7+/-1.5 years); and at Surrey, 138 Caucasian women (61.4+/-4.5 years) and 35 Asian women (59.9+/-6.4 years) had serum 25(OH)D measured by IDS enzyme immunoassay. In winter/spring none of the Caucasian women living in Surrey had 25(OH)D<20 nmol/L, but nearly a quarter of women in Aberdeen were vitamin D deficient. This number decreased to 4.2% in summer/autumn. For the Asian women 17.1% were vitamin D-deficient in summer, increasing to 58.1% in winter. Using higher 25(OH)D deficiency cut-offs, the percentage of women affected was much higher. These longitudinal data show clear differences in vitamin D status between the north and south of the UK, and marked ethnic differences. They are consistent with our previous data and with cross-sectional data from the 1958 birth cohort. The low vitamin D status may have implications for bone health and other health outcomes, which is currently being investigated in this publication group. The extent of vitamin D deficiency in Asian women residing in the South of England is of concern. PMID- 20302935 TI - Standardization of testosterone measurements in humans. AB - Testosterone levels are used primarily for the diagnosis of hypogonadism in men and androgen excess in women. Current studies suggest that serum testosterone measurements may be indicated in a wide range of diseases and conditions. Translation of testosterone levels outside of the reference ranges into clinical treatment, appropriate cut offs for clinical guidelines and epidemiological studies with public health impact pose challenges due to the measurement variability among assays and in assay sensitivity. While introducing mass spectrometry technology can overcome some of these challenges and help to improve measurements, it faces variability issues similar to those observed with immunoassays that need to be addressed. To overcome these problems in testosterone testing, the Centers for Disease Control and Prevention, National Center for Environmental Health, Division of Laboratory Sciences (CDC/NCEH/DLS) started a steroid hormone standardization project. Their objective was to create testosterone measurement results that are traceable to one accuracy basis, thus allowing measurements to be comparable across methods, time, and location. CDC/NCEH/DLS conducts activities to standardize and improve testosterone assays and laboratory measurements by establishing metrological traceability to a higher order reference method and material. In addition, the standardization effort includes pre- and post-analytical challenges, such as test selection, interpretation, and establishing reference ranges to improve the translation of standardized results into clinical guidelines and public health assessments. CDC is conducting these standardization activities in collaboration with the clinical, laboratory, and research communities. PMID- 20302936 TI - Highly sensitive and specific analysis of sterol profiles in biological samples by HPLC-ESI-MS/MS. AB - High-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) is a powerful method for the microanalysis of compounds in biological samples. Compared with gas chromatography-mass spectrometry (GC-MS), this method is more broadly applicable to various compounds and usually does not require a derivatization step before analysis. However, when neutral sterols are analyzed, the sensitivities of usual HPLC-MS/MS method are not superior to those of GC-MS because the sterols are relatively resistant to ionization. In this review, we introduce the recent development of HPLC-MS/MS analysis for the quantification of non-cholesterol sterols. By adding an effective derivatization step to the conventional procedure, sterol analysis by HPLC-MS/MS surpassed that obtained by GC-MS in sensitivity. In addition, sufficient specificity of this method was achieved by selected reaction monitoring (SRM) and thorough chromatographic separation of each sterol. PMID- 20302937 TI - Preclinical challenges in steroid analysis of human samples. AB - Preclinical challenges in the analysis of steroid hormones are primarily determined by biological factors involved in the physiology and pathophysiology of hormone secretion. Major biologically influencing factors like age, sex, pubertal stage, pregnancy, phase of the menstruation, and diurnal rhythm have to be considered in the definition of reference ranges for steroids and their clinical interpretation. Hitherto, in clinical routine laboratories steroids were mainly determined by direct immunoassays applied on automated platforms, which are simple, rapid and cheap if a high number of samples are measured. However, technical factors like cross-reactivity of related steroid metabolites or limited analytical ranges have to be taken in account and may impair accuracy and precision of these direct methods. The actual development of mass spectrometry based analytical platforms for the determination of single steroid or steroid patterns seems to be an alternative analytical approach combining multi parametric analysis, high sensitivity and specificity as well simple sample pre treatment, robustness and low running costs for steroid analysis. This short review will give an overview about biological influencing factors and technical disturbing factors of routinely used immunoassay for the analysis of steroids. The application of LC-MS/MS as an alternative routine high-throughput platform for steroid analysis and its perspective role in the standardization and harmonisation of steroid measurements in clinical routine application will be discussed. PMID- 20302938 TI - Proficiency testing of 25-hydroxyvitamin D (25-OHD) assays. AB - The Vitamin D External Quality Assessment Scheme (DEQAS) has been monitoring 25 OHD assay performance since 1989. The scheme has expanded rapidly in recent years and has 670 participants in 35 countries (July 2009). Five samples of human serum are distributed quarterly and the results analyzed to give an All-Laboratory Trimmed Mean (ALTM) and SD. Each participant has internet access to a preliminary report after submission of results and, following the results deadline, a final report is e-mailed to designated staff in each laboratory. The last 15 years has seen an improvement in mean inter-laboratory imprecision (CV), from 32.0% (1994) to 15.3% (2009) and most major methods are now giving results within plus or minus 7.4% of the ALTM (2009). DEQAS has regularly conducted and reported on a number of investigations into the performance of 25-OHD methods. A gas chromatography-mass spectrometry (GC-MS) reference method for 25-OHD is under development and will be used to assess whether the ALTM remains the most appropriate target for DEQAS samples. PMID- 20302939 TI - Alzheimer's disease and tauopathy studies in flies and worms. AB - Progressive dementias like Alzheimer's Disease (AD) and other tauopathies are an increasing threat to human health worldwide. Although significant progress has been made in understanding the pathogenesis of these diseases using cell culture and mouse models, the complexity of these diseases has still prevented a comprehensive understanding of their underlying causes. As with other neurological diseases, invertebrate models have provided novel genetic approaches for investigating the molecular pathways that are affected in tauopathies, including AD. This review focuses on transgenic models that have been established in Drosophila melanogaster and Caenorhabditis elegans to investigate these diseases, and the insights that have been gained from these studies. Also included are a brief description of the endogenous versions of human "disease genes" (like tau and the Amyloid Precursor Protein) that are expressed in invertebrates, and an overview of results that have been obtained from animals lacking or overexpressing these genes. These diverse models can be used to advance our knowledge about how these proteins acquire a pathogenic function and how disrupting their normal functions may contribute to neurological pathologies. They also provide powerful assays for identifying molecular and genetic interactions that are important in developing or preventing the deleterious effects. PMID- 20302941 TI - A novel TWO-STEP renaturation procedure for efficient production of recombinant BMP-2. AB - Bone morphogenetic proteins (BMPs) stimulate bone formation and thus constitute important protein therapeutics. Here, a novel procedure is presented which allows fast and efficient production of biologically active BMP-2 via a TWO-STEP procedure: the conditions are designed such that the first step favors formation of monomeric species with the correct intramolecular disulfide bridges, the conditions of the second folding reaction stimulate the formation of the intermolecular disulfide bridge. The short processing times and increased yields compared to previously published procedures allow low-cost production of this important protein drug. PMID- 20302942 TI - High-yield expression of human vascular endothelial growth factor VEGF(165) in Escherichia coli and purification for therapeutic applications. AB - Vascular endothelial growth factor (VEGF(165)) is a potent mitogen that induces angiogenesis and vascular permeability in vivo and has demonstrated potential in therapeutic applications for accelerating wound healing. An industrial production method that provides high yield as well as high purity, quality, and potency is needed. The process described in this report involves a bacterial expression system capable of producing approximately 9g of rhVEGF per liter of broth and a downstream purification process consisting of protein refolding and three chromatography steps prior to formulation of the drug substance. A high cell density (HCD) fed-batch fermentation process was used to produce rhVEGF in periplasmic inclusion bodies. The inclusion bodies are harvested from the cell lysate and subjected to a single-step protein solubilization and refolding operation to extract the rhVEGF for purification. Overall recovery yields observed during development, including refolding and chromatography, were 30+/ 6%. Host cell impurities are consistently cleared below target levels at both laboratory and large-scale demonstrating process robustness. The structure of the refolded and purified rhVEGF was confirmed by mass spectrometry, N-terminal sequencing, and tryptic peptide mapping while product variants were analyzed by multiple HPLC assays. Biological activity was verified by the proliferation of human umbilical vein derived endothelial cells. PMID- 20302943 TI - Synthesis of human renalase1 in Escherichia coli and its purification as a FAD containing holoprotein. AB - Renalase is a protein ubiquitous in vertebrates, which has been proposed to modulate blood pressure and heart rate, and whose downregulation might result in hypertension. Despite its potential relevance for human health, the biochemical characterization of renalase is still lacking, possibly due to difficulties in obtaining it in recombinant form. By expressing two different gene constructs, we found that the major isoform of human renalase, renalase1, is mainly produced in Escherichia coli in inclusion bodies. However, by optimizing the expression conditions, significant amounts of soluble products were obtained. Both soluble renalase forms have been purified to homogeneity exploiting their N-terminal His tag. Linking of the protein of interest to the SUMO protein did not improve solubility, but yielded untagged renalase1 after proteolytic processing of the fusion product. The two recombinant renalase forms displayed the same molecular properties. They bind equimolar amounts of FAD and appear to be correctly folded by various criteria. The procedures for the production and isolation of recombinant renalase1 here reported are expected to boost the much awaited biochemical studies on this remarkable protein. PMID- 20302940 TI - Molecular insights and therapeutic targets for blood-brain barrier disruption in ischemic stroke: critical role of matrix metalloproteinases and tissue-type plasminogen activator. AB - Blood-brain barrier (BBB) disruption, mediated through matrix metalloproteinases (MMPs) and other mechanisms, is a critical event during ischemic stroke. Tissue plasminogen activator (tPA) is the only FDA-approved thrombolytic therapy for acute ischemic stroke, but the efficacy and safety of its therapeutic application are limited by narrow treatment time windows and side effects. Thus, there is a pressing need to develop combinational therapy that could offset tPA side effects and improve efficacy in clinical practice. Recent experimental studies indicate that tPA has previously unidentified functions in the brain beyond its well established thrombolytic activity, which might contribute to tPA-related side effects through MMPs (mainly MMP-9) and several signaling pathways involved in LDL receptor-related protein (LRP), activated protein C (APC) and protease activated receptor 1 (PAR-1), platelet-derived growth factor C (PDGF-C), and N methyl-d-aspartate (NMDA) receptor. Therapeutic targeting of MMPs and/or tPA related signaling pathways might offer promising new approaches to combination therapies for ischemic stroke. This review provides an overview of the relationship between structural components and function of the BBB/neurovascular unit with respect to ischemic stroke. We discuss how MMPs and tPA contribute to BBB disruption during ischemic stroke and highlight recent findings of molecular signaling pathways involved in neurotoxicity of tPA therapy. PMID- 20302945 TI - Neural basis of extraordinary empathy and altruistic motivation. AB - A central evolutionary challenge for social groups is uniting a heterogeneous set of individuals towards common goals. One means by which social groups form and endure is by endowing group members with extraordinary prosocial proclivities, such as ingroup love, towards other group members. Here we examined the neural basis of extraordinary empathy and altruistic motivation in African-American and Caucasian-American individuals using functional magnetic resonance imaging. Our results indicate that empathy for ingroup members is neurally distinct from empathy for humankind, more generally. People showed greater response within anterior cingulate cortex and bilateral insula when observing the suffering of others, but African-American individuals additionally recruit medial prefrontal cortex when observing the suffering of members of their own social group. Moreover, neural activity within medial prefrontal cortex in response to pain expressed by ingroup relative to outgroup members predicted greater empathy and altruistic motivation for one's ingroup, suggesting that neurocognitive processes associated with self identity underlie extraordinary empathy and altruistic motivation for members of one's own social group. Taken together, our findings reveal distinct neural mechanisms of empathy and altruistic motivation in an intergroup context and may serve as a foundation for future research investigating the neural bases of intergroup prosociality, more broadly construed. PMID- 20302946 TI - Decreased activation of lateral orbitofrontal cortex during risky choices under uncertainty is associated with disadvantageous decision-making and suicidal behavior. AB - Decision-making impairment has been linked to orbitofrontal cortex lesions and to different disorders including substance abuse, aggression and suicidal behavior. Understanding the neurocognitive mechanisms of these impairments could facilitate the development of effective treatments. In the current study, we aimed to explore the neural and cognitive basis of poor decision-making ability associated with the vulnerability to suicidal behavior, a public health issue in most western countries. Twenty-five not currently depressed male patients, 13 of whom had a history of suicidal acts (suicide attempters) and 12 of whom had none (affective controls), performed an adapted version of the Iowa Gambling Task during functional Magnetic Resonance Imaging. Task-related functional Regions-of Interest were independently defined in 15 male healthy controls performing the same task (Lawrence et al., 2009). In comparison to affective controls, suicide attempters showed 1) poorer performance on the gambling task 2) decreased activation during risky relative to safe choices in left lateral orbitofrontal and occipital cortices 3) no difference for the contrast between wins and losses. Altered processing of risk under conditions of uncertainty, associated with left lateral orbitofrontal cortex dysfunction, could explain the decision-making deficits observed in suicide attempters. These impaired cognitive and neural processes may represent future predictive markers and therapeutic targets in a field where identification of those at risk is poor and specific treatments are lacking. These results also add to our growing understanding of the role of the orbitofrontal cortex in decision-making and psychopathology. PMID- 20302944 TI - Phonetically irregular word pronunciation and cortical thickness in the adult brain. AB - Accurate pronunciation of phonetically irregular words (exception words) requires prior exposure to unique relationships between orthographic and phonemic features. Whether such word knowledge is accompanied by structural variation in areas associated with orthographic-to-phonemic transformations has not been investigated. We used high-resolution MRI to determine whether performance on a visual word-reading test composed of phonetically irregular words, the Wechsler Test of Adult Reading (WTAR), is associated with regional variations in cortical structure. A sample of 60 right-handed, neurologically intact individuals were administered the WTAR and underwent 3T volumetric MRI. Using quantitative, surface-based image analysis, cortical thickness was estimated at each vertex on the cortical mantle and correlated with WTAR scores while controlling for age. Higher scores on the WTAR were associated with thicker cortex in bilateral anterior superior temporal gyrus, bilateral angular gyrus/posterior superior temporal gyrus, and left hemisphere intraparietal sulcus. Higher scores were also associated with thinner cortex in left hemisphere posterior fusiform gyrus and central sulcus, bilateral inferior frontal gyrus, and right hemisphere lingual gyrus and supramarginal gyrus. These results suggest that the ability to correctly pronounce phonetically irregular words is associated with structural variations in cortical areas that are commonly activated in functional neuroimaging studies of word reading, including areas associated with grapheme-to phonemic conversion. PMID- 20302948 TI - Purely endogenous capture of attention by task-defining features proceeds independently from spatial attention. AB - Attention can be focused voluntarily and effectively on spatial locations in order to enhance the processing of task-relevant events. However, work on 'attentional capture' has demonstrated that spatial biases can be temporarily reset by transient and salient stimuli, especially if they share defining characteristics with the targets of a task goal. In the current study, we investigated whether the appearance of stimuli containing task-defining features at an unattended location was sufficient to capture attention, even when these were not perceptually salient. We used event-related-potential (ERP) markers to test whether the selection of task-defining features was modulated by top-down spatial attention, and to test whether the appearance of 'unattended targets' transiently disrupted the spatial bias. Surprisingly, the results revealed that ERP markers of selection of task-defining features were equivalent for stimuli appearing at spatially attended and unattended locations. In addition, the presentation of task-defining stimuli at the spatially unattended location induced a short-lived redistribution of the pre-established spatial attention bias toward the 'capture' side. These findings show that task-defining features of a stimulus are automatically processed independently from spatial attention, and suggest the co-existence of multiple sources of top-down biasing signals, which might in part sustain the capture mechanism. PMID- 20302947 TI - Brain activity during bladder filling is related to white matter structural changes in older women with urinary incontinence. AB - Evidence from longitudinal studies in community-dwelling elderly links complaints of urgency and urinary incontinence with structural white matter changes known as white matter hyperintensities (WMH). How WMH might lead to incontinence remains unknown, since information about how they relate to neural circuits involved in continence control is lacking. The aim of this study was to investigate the role of WMH in altered brain activity in older women with urgency incontinence. In a cross-sectional study, we measured WMH, globally and in specific white matter tracts, and correlated them with regional brain activity measured by fMRI (combined with simultaneous urodynamic monitoring) during bladder filling and reported 'urgency'. We postulated that increase in global WMH burden would be associated with changes (either attenuation or reinforcement) in responses to bladder filling in brain regions involved in bladder control. Secondly, we proposed that such apparent effects of global WMH burden might be specifically related to the burden in a few critical white matter pathways. The results showed that regional activations (e.g. medial/superior frontal gyrus adjacent to dorsal ACG) and deactivations (e.g. perigenual ACG adjacent to ventromedial prefrontal cortex) became more prominent with increased global WMH burden, suggesting that activity aimed at suppressing urgency was augmented. Secondary analyses confirmed that the apparent effect of global WMH burden might reflect the presence of WMH in specific pathways (anterior thalamic radiation and superior longitudinal fasciculus), thus affecting connections between key regions and suggesting possible mechanisms involved in continence control. PMID- 20302949 TI - Predicting variations of perceptual performance across individuals from neural activity using pattern classifiers. AB - Within the past decade computational approaches adopted from the field of machine learning have provided neuroscientists with powerful new tools for analyzing neural data. For instance, previous studies have applied pattern classification algorithms to electroencephalography data to predict the category of presented visual stimuli, human observer decision choices and task difficulty. Here, we quantitatively compare the ability of pattern classifiers and three ERP metrics (peak amplitude, mean amplitude, and onset latency of the face-selective N170) to predict variations across individuals' behavioral performance in a difficult perceptual task identifying images of faces and cars embedded in noise. We investigate three different pattern classifiers (Classwise Principal Component Analysis, CPCA; Linear Discriminant Analysis, LDA; and Support Vector Machine, SVM), five training methods differing in the selection of training data sets and three analyses procedures for the ERP measures. We show that all three pattern classifier algorithms surpass traditional ERP measurements in their ability to predict individual differences in performance. Although the differences across pattern classifiers were not large, the CPCA method with training data sets restricted to EEG activity for trials in which observers expressed high confidence about their decisions performed the highest at predicting perceptual performance of observers. We also show that the neural activity predicting the performance across individuals was distributed through time starting at 120ms, and unlike the face-selective ERP response, sustained for more than 400ms after stimulus presentation, indicating that both early and late components contain information correlated with observers' behavioral performance. Together, our results further demonstrate the potential of pattern classifiers compared to more traditional ERP techniques as an analysis tool for modeling spatiotemporal dynamics of the human brain and relating neural activity to behavior. PMID- 20302950 TI - Size and probability of rewards modulate the feedback error-related negativity associated with wins but not losses in a monetarily rewarded gambling task. AB - Feedback error-related negativity (fERN) has been referred to as a negative deflection in the event related potential (ERP), which distinguishes between wins and losses in terms of expected and unexpected outcomes. Some studies refer to the "expected outcome" as the probability to win vs. to lose, and others as expected size of rewards. We still do not know much about whether these alternative interpretations of "expected outcome" affect the fERN in a different manner, nor do we know the effect of their interaction in an expected value fashion. We set a gambling task with four game categories; two had the same expected value, while the other two categories were equivalent to the first ones, but alternatively in the size or probability of the offered rewards. Results show that fERN preceded by a P200, and followed by a Pe-like wave differentiates between losing in the category with a higher expected value and the rest of the experimental conditions. fERN differentiates between wins and losses, but changes in the size and probability of rewards impact the fERN amplitude only in win conditions. Results also show greater positivity following win feedback when the size and/or probability of the outcome rewards were higher, so that the higher the expected value the greater the positivity following win feedback. Our findings support the notion that both the probability and size of the offered rewards modulate the motivational value for the win feedback, this being also true for their interaction in an expected value fashion. PMID- 20302951 TI - Recomposing a fragmented literature: how conditional and relational arguments engage different neural systems for deductive reasoning. AB - Deductive reasoning is traditionally viewed as a unitary process involving either rule-based or visuo-spatial mechanisms. However, there is a disagreement in the neuroimaging literature on whether the data support one alternative over the other. Here we test the hypothesis that discrepancies in the literature result from the reasoning materials themselves. Using functional magnetic resonance imaging, we measure brain activity of participants while they integrate the premises of conditional arguments (primarily Modus Tollens: If P then Q; not-Q) and Relational Syllogisms (i.e., linear arguments of the sort P is to the left of Q; Q is to the left of R). We find that reasoning with Modus Tollens activates the left inferior frontal gyrus to a greater extent than the Relational Syllogisms. In contrast, the Relational Syllogisms engage the right temporo parieto-occipital junction more than conditional arguments. This suggests that conditional reasoning relies more on so-called syntactic processes than relational reasoning, while relational reasoning may rely on visuo-spatial processes and mental imagery more than conditional reasoning. This investigative approach, together with its results, clarifies some apparently inconsistent findings in this literature by showing that the nature of the logical argument, whether it is relational or conditional, determines which neural system is engaged. PMID- 20302952 TI - Identification of new molecular markers for assembling the eukaryotic tree of life. AB - Six eukaryotic supergroups have been proposed based on both morphological and molecular data. However, some of these supergroups are contentious and the deep relationships among them are poorly resolved. This is due to a limited number of morphological characters and few molecular markers in current use. The lack of resolution in most multigene analyses, including phylogenomic analyses, necessitates a search for additional, appropriate molecular markers to enable targeted sampling of taxa in key phylogenetic positions. We evaluated the phylogenetic signal of 860 proteins obtained from the Clusters of Orthologous Groups of proteins (COGs) database. We report a total of 17 markers that resulted in well-resolved topologies that are congruent with well-established components of the eukaryotic tree. To establish their utility, we designed universal degenerate primers for six markers, some of which showed promising results in unicellular eukaryotes. Finally, we present phylogenetic informativeness profiles for seven selected markers, revealing that the markers contain phylogenetic signal that spans the whole tree including the deeper branches. PMID- 20302953 TI - Erosion of phylogenetic signal in tunicate mitochondrial genomes on different levels of analysis. AB - The molecular phylogenetic position of Tunicata and internal interrelationship of higher tunicate taxa is controversial. High substitution rates and extreme gene order variability hamper phylogenetic analyses. We describe the sequence and organization of the mitochondrial genome of the aplousobranch ascidian Clavelina lepadiformis and use mitochondrial genomes to investigate phylogenetic information content on different molecular levels of comparison. Despite agreement in phylogenetic analyses of nucleotide and amino acid sequences, split analyses revealed little phylogenetic signal. Split analyses on molecular data sets deemed increasingly conservative, demonstrated that the lack of signal pervades all levels and that it is Tunicata the taxon of interest that introduces noise in the data sets. The strongest signal present in our molecular data sets as revealed by split analyses is not present in the optimal cladograms and supports a sister group relationship between cephalochordates and craniates. Phylogenetic analysis of gene order using common interval algorithms shows that phylogenetic signal is also eroded in respect of gene positions. Even functional constraints, such as partial gene overlap as exemplified in the case of the commonly observed adjacency between cox2 and cytb are subjected to homoplasy. However, rare phylogenetic events like this hold some promise to retain phylogenetic information even in such cases of extreme variability. We therefore caution to rely on sequence analysis alone and recommend investigation into the signal content of molecular data sets in order to assess the strength of phylogenetic signal. PMID- 20302954 TI - Towards an assessment of character interdependence in avian RNA phylogenetics: a general secondary structure model for the avian mitochondrial 16S rRNA. PMID- 20302955 TI - Phylogeographic analysis and environmental niche modeling of the plain-bellied watersnake (Nerodia erythrogaster) reveals low levels of genetic and ecological differentiation. AB - Species that exhibit geographically defined phenotypic variation traditionally have been divided into subspecies. Subspecies based on phenotypic features may not comprise monophyletic groups due to selection, gene flow, and/or convergent evolution. In many taxonomic groups the number of species once designated as widespread is dwindling rapidly, and many workers reject the concept of subspecies altogether. We tested whether currently recognized subspecies in the plain-bellied watersnake Nerodia erythrogaster are concordant with relationships based on mitochondrial markers, and whether it represents a single widespread species. The range of this taxon spans multiple potential biogeographic barriers (especially the Mississippi and Apalachicola Rivers) that correspond with lineage breaks in many species, including other snakes. We sequenced three mitochondrial genes (NADH-II, Cyt-b, Cox-I) from 156 geo-referenced specimens and developed ecological niche models using Maxent and spatially explicit climate data to examine historical and ecological factors affecting variation in N. erythrogaster across its range. Overall, we found little support for the recognized subspecies as either independent evolutionary lineages or geographically circumscribed units and conclude that although some genetic and niche differentiation has occurred, most populations assigned to N. erythrogaster appear to represent a single, widespread species. However, additional sampling and application of nuclear markers are necessary to clarify the status of the easternmost populations. PMID- 20302956 TI - Mitochondrial phylogeography of the Bedriaga's rock lizard, Archaeolacerta bedriagae (Reptilia: Lacertidae) endemic to Corsica and Sardinia. AB - Archaeolacerta bedriagae is a rock-dwelling lizard endemic to the Corso-Sardinian insular system. We investigated the phylogeography of the species by using the mitochondrial ND4 and flanking tRNAs genes from 94 specimens belonging to 19 populations. Phylogenetic, Barrier, and SAMOVA analyses revealed a highly structured pattern characterized by two levels of discontinuities in the geographical distribution of mtDNA diversity: (i) a deep phylogeographic break in Northern Corsica between Lineage A, restricted to northernmost Corsica, and Lineage B widespread all over the remaining range of the species, and (ii) some minor phylogeographic discontinuities within lineage B, which is sub-structured into six closely related haplotype clades with remarkable concordance with geography. The first evolutionary event concerning the split between the two main lineages from an ancestral population occurred in the Upper Pliocene (5.87-3.68 mya), while the divergence within lineage B would have started from the Upper Pleistocene (2.5-1.6 mya), between Corsican and Sardinian populations. Somewhat later (1.7-1.1 mya), the Sardinian ancestral population underwent fragmentation into population groups inhabiting North, Central, and South Sardinia. As inferred from previous allozyme surveys, the divergence among population groups would be driven by allopatric fragmentation, while the discrepancy concerning the major partition into two lineages inferred from mtDNA but not apparent in analysis of allozymes needs further investigation. PMID- 20302957 TI - Phylogenetic relationships of megophryid frogs of the genus Leptobrachium (Amphibia, Anura) as revealed by mtDNA gene sequences. AB - By investigating genealogical relationships, we estimated the phylogenetic history and biogeography in the megophryid genus Leptobrachium (sensu lato, including Vibrissaphora) from southern China, Indochina, Thailand and the Sundaland. The genealogical relationships among the 30 named and unnamed taxa were estimated using 2009 bp of sequences from the mitochondrial DNA genes 12S rRNA, tRNA(val), and 16S rRNA using maximum parsimony, maximum likelihood, and Bayesian inference methods. The genus Leptobrachium was a well-supported monophyletic group that contained two major clades. One clade had three subclades primarily from disjunct regions including Borneo, Peninsular Malaysia and Java, and Thailand. The Bornean subclade included one species each from the Philippines and Sumatra. The other major clade consisted of two subclades, one from Indochina and the other from southern China (Vibrissaphora). Divergence times estimated an old evolutionary history of each subclade, one that could not be explained by the geohistory of Southeast Asian major landmasses. PMID- 20302958 TI - Donor KIR Genes 2DL5A, 2DS1 and 3DS1 are associated with a reduced rate of leukemia relapse after HLA-identical sibling stem cell transplantation for acute myeloid leukemia but not other hematologic malignancies. AB - Stem cell transplantation (SCT) from a healthy donor can be curative for patients with hematologic malignancies resistant to other treatments. Elimination of malignant cells through a graft-versus-leukemia (GVL) effect involves donor T and natural killer (NK) cells, but their relative contribution to this process is poorly defined. NK cell alloreactivity and GVL effects are controlled by the nature of the interaction of NK activation receptors and killer-immunoglobulin like-receptors (KIR) with major histocompatibility locus class I antigens on the target cell. We performed KIR-genotyping of HLA-identical sibling donors in 246 T cell-depleted SCTs to identify genetic factors affecting transplant outcome (treatment-related mortality [TRM], leukemic relapse, and survival). Univariate and multivariate analysis of transplant-related risk factors and KIR genotyping was performed to identify independent variables predictive of outcome for different forms of leukemia. Further to confirming known predictive factors for TRM and survival (CD34 cell dose, patient age, disease stage), statistical analysis revealed that 3 donor B haplotype KIR genes, 2DL5A, 2DS1, and 3DS1, were associated with significantly less relapse in patients with acute myelogenous leukemia (AML) (13% versus 57%) but not in patients with other myelogenous or lymphoid malignancies. AML patients receiving SCT from donors with these KIR genes relapsed 4 times less frequently than patients transplanted from donors with other KIR genotypes. These findings suggest specific, genetically determined, interactions between NK cells and AML cells that facilitate the GVL effect, and have implications for donor selection for AML patients. PMID- 20302959 TI - Favorable outcomes in patients surviving 5 or more years after allogeneic hematopoietic stem cell transplantation for hematologic malignancies. AB - Allogeneic hematopoietic stem cell transplantation (HSCT) is a curative treatment for some hematologic malignancies. As the overall number of survivors continues to increase, studies systematically examining outcomes in long-term survivors are needed. We studied the clinical and quality-of-life outcomes in HSCT recipients surviving 5 or more years from HSCT. Since 1993, 262 patients with hematologic malignancies received a T cell-depleted myeloablative HSCT from an HLA-identical sibling at a single center. Ninety-two survived beyond 5 years from HSCT (median follow-up 9.4 years, range: 5.1-15.3). Median age at transplantation was 35 years (range: 10-56). Twenty-two (24%) received a bone marrow transplant, and 70 (76%) received a peripheral blood HSCT. Of the 92 survivors, 60 completed quality-of life measures. The main outcomes examined were chronic graft-versus-host-disease, disease relapse, survival, health-related quality-of-life (HRQL) (Functional Assessment of Cancer Therapy-General), physical and mental health (SF-36), and symptom experience (Rotterdam Symptom Checklist). Seventy-five (82%) of 92 survivors no longer required systemic immunosuppressive treatment. Four (4.3%) relapsed with leukemia at a median of 8.5 years (range: 6.2-14.0) after HSCT. Four (4.3%) died between 7.4 and 13.4 years post-HSCT (1 relapse, 1 lung cancer, 1 pneumonia, 1 brain hemorrhage). Most survivors beyond 5 years had an excellent performance status with no difference in physical and mental health and higher HRQL scores (P = .02) compared with population norms. Although physical and psychologic symptom distress was low, those with higher symptom distress experienced inferior HRQL. These results show that 5 or more years after T cell depleted HSCT for hematologic malignancy most individuals survive disease free with an excellent performance status, preserved physical and psychological health, and excellent HRQL. PMID- 20302960 TI - Reduced-intensity conditioning regimens for allogeneic transplantation in children with acute lymphoblastic leukemia. AB - Reduced-intensity conditioning regimens have been used extensively in adults with hematologic malignancies. To address whether this is a feasible approach for children with acute lymphoblastic leukemia, we evaluated transplant outcomes in 38 recipients transplanted from 1995-2005 for whom this was their first transplant. The median age at transplant was 12 years, and 47% had performance scores <90%. Disease status was first complete remission (CR) in 13%, > or =CR2 in 60% of patients, and 22% had active disease at transplantation. Matched related donors were available for a third of patients, about half of whom received bone marrow (BM) and the others, peripheral blood progenitor cells. Sixty percent of unrelated donor transplant recipients received peripheral blood progenitor cells. The day-100 probability of grade II-IV acute graft-versus-host disease was 37% and the 3-year probability of chronic graft-versus-host disease, 26%. At 3 years, the probability of treatment-related mortality was 40%, relapse 37%, and disease-free survival 30%. These data indicate long-term DFS can be achieved using reduced-intensity conditioning regimens in children with acute lymphoblastic leukemia. Given the relatively small cohort, these findings must be validated in a larger population. PMID- 20302961 TI - Unmanipulated HLA-mismatched/haploidentical blood and marrow hematopoietic stem cell transplantation. AB - Extensive ex vivo T cell-depleted or unmanipulated haploidentical transplantation provides benefits of rapid and near universal donor availability for patients without HLA-identical sibling donors or those who urgently need transplant. However, CD34 selected haplotype mismatched transplantation was limited by delayed immune reconstitution (IR), although this protocol has now been an acceptable approach. Recently, Peking University researchers developed a novel approach to HLA-mismatched/haploidentical blood and marrow transplantation without in vitro T cell depletion (GIAC protocol). This review summarizes transplant outcomes, and factors correlating with transplant outcomes following the GIAC protocol. Moreover, future challenges in improving posttransplant IR and finding the best approach reducing the incidence and severity of GVHD, whereas preserving graft-versus-leukemia effect to prevent the recurrence of underlying malignancy, are also discussed. PMID- 20302962 TI - Time to consider HPV vaccination after allogeneic stem cell transplantation. AB - Squamous cell carcinoma (SCC) is among the most common secondary cancers after allogeneic stem cell transplantation (allo-SCT). Several types of human papillomavirus (HPV) are causally linked with SCC of the genital tract and head and neck, and the incidence of these cancers is higher among immunosuppressed patients compared to immunocompetent patients. In June 2006, a quadrivalent HPV vaccine was approved by the Food and Drug Administration (FDA) for females aged 9 to 26 years to prevent cervical warts and vulvar, vaginal, and cervical cancer. FDA approval was granted in October 2009 for males aged 9 to 26 years to prevent genital warts. The quadrivalent HPV vaccine is now available for off-label use, and may be beneficial to patients after allo-SCT. It is time to evaluate the immunogenicity and efficacy in preventing HPV-related squamous cell carcinoma in this population. PMID- 20302963 TI - Corticosteroid dose as a risk factor for avascular necrosis of the bone after hematopoietic cell transplantation. AB - Exposure to corticosteroids increases the risks of avascular necrosis (AVN) of the bone after hematopoietic cell transplantation (HCT). However, whether this effect is dependent on the dose of corticosteroids is not well known. We conducted a case-controlled study, which included 74 recipients of autologous or allogeneic HCT with AVN and 147 controls without AVN that were matched by age, sex, and year of HCT to cases. Cases with AVN included 8 autologous HCT recipients, 58 myeloablative allogeneic HCT recipients, and 8 recipients of non myeloablative allogeneic HCT. Corticosteroid exposure was expressed as cumulative doses of prednisone. Cases received higher cumulative doses of prednisone than controls, and among allogeneic HCT recipients, cases were more likely to have developed acute and chronic graft-versus-host disease (aGVHD, cGVHD). Cumulative dose of prednisone was an independent risk factor for AVN. Compared to no corticosteroid exposure, exposure to <3870 mg cumulative dose of prednisone was associated with 4.0 (95% confidence intervals, 1.5-11.2) times higher risk, 3870 9735 mg with 5.6 (2.1-15.2) times higher risk and >9735 with 8.6 (3.2-23.5) times higher risk of AVN. Exposure to higher doses of corticosteroids increases the risk of AVN in HCT recipients. PMID- 20302964 TI - Frequency of CD4(+)CD25(hi)FOXP3(+) regulatory T cells has diagnostic and prognostic value as a biomarker for acute graft-versus-host-disease. AB - The relationship between regulatory T cells (Tregs) and acute graft-versus-host disease (aGVHD) in clinical allogeneic bone marrow transplantation (BMT) recipients is not well established. We conducted a prospective analysis of peripheral blood Tregs as determined by the frequency of CD4(+)CD25(hi)FOXP3(+) lymphocytes in 215 BMT patients. Autologous BMT patients (N = 90) and allogeneic BMT patients without GVHD (N = 65) had similar Treg frequencies, whereas allogeneic patients with GVHD (N = 60) had Treg frequencies that were 40% less than those without GVHD. Treg frequencies decreased linearly with increasing grades of GVHD at onset, and correlated with eventual maximum grade of GVHD (P < .001). In addition, frequency of Tregs at onset of GVHD predicted the response to GVHD treatment (P = .003). Patients with Treg frequencies less than the median had higher nonrelapse mortality (NRM) than patients with Tregs greater than the median, but experienced equivalent relapse mortality, resulting in an inferior survival at 2 years (38% versus 63%, P = .03). Treg frequency may therefore have important prognostic value as a biomarker of aGVHD. PMID- 20302965 TI - Visualization of F-actin localization and dynamics with live cell markers in Neurospora crassa. AB - Filamentous actin (F-actin) plays essential roles in filamentous fungi, as in all other eukaryotes, in a wide variety of cellular processes including cell growth, intracellular motility, and cytokinesis. We visualized F-actin organization and dynamics in living Neurospora crassa cells via confocal microscopy of growing hyphae expressing GFP fusions with homologues of the actin-binding proteins fimbrin (FIM) and tropomyosin (TPM-1), a subunit of the Arp2/3 complex (ARP-3) and a recently developed live cell F-actin marker, Lifeact (ABP140 of Saccharomyces cerevisiae). FIM-GFP, ARP-3-GFP, and Lifeact-GFP associated with small patches in the cortical cytoplasm that were concentrated in a subapical ring, which appeared similar for all three markers but was broadest in hyphae expressing Lifeact-GFP. These cortical patches were short-lived, and a subset was mobile throughout the hypha, exhibiting both anterograde and retrograde motility. TPM-1-GFP and Lifeact-GFP co-localized within the Spitzenkorper (Spk) core at the hyphal apex, and were also observed in actin cables throughout the hypha. All GFP fusion proteins studied were also transiently localized at septa: Lifeact-GFP first appeared as a broad ring during early stages of contractile ring formation and later coalesced into a sharper ring, TPM-1-GFP was observed in maturing septa, and FIM-GFP/ARP3-GFP-labeled cortical patches formed a double ring flanking the septa. Our observations suggest that each of the N. crassa F-actin binding proteins analyzed associates with a different subset of F-actin structures, presumably reflecting distinct roles in F-actin organization and dynamics. Moreover, Lifeact-GFP marked the broadest spectrum of F-actin structures; it may serve as a global live cell marker for F-actin in filamentous fungi. PMID- 20302966 TI - Acute effects of 2-methoxyestradiol on endothelial aortic No release in male and ovariectomized female rats. AB - The endogenous metabolites of 17beta-estradiol are thought to have protective vascular effects, especially in males and estrogen-deprived females. The present study evaluated the acute in vitro effects of the active metabolite 2 methoxyestradiol on endothelial NO release from ovariectomized female and intact male and female rat aortas. NO was measured electrochemically by differential normal pulse amperometry using carbon fiber microsensors, and also by fluorescence microscopy using 4,5-diaminofluorescein diacetate. 2 Methoxyestradiol alone induced a maintained increase in endothelial NO release in male and ovariectomized rats that was reduced by pretreatment with L-NAME. NO release induced by calcium ionophore alone (A23187) was lower in aortas from ovariectomized rats than from intact females, indicating that estrogen deprivation induces endothelial dysfunction. Pretreatment of aortas with 2 methoxyestradiol potentiated significantly the A23187-induced-NO release in ovariectomized as well as in males, but not in intact females. This potentiation was reduced or abolished by L-NAME. 2-Methoxyestradiol potentiated the vasodilatory effect of A23187 on intestinal arterioles, and also increased intestinal tissular laser-Doppler blood flow signal. These results demonstrate that 17beta-estradiol and its active metabolite 2-methoxyestradiol increase basal aortic endothelial NO production and also cause a potentiation of the calcium ionophore-stimulated NO release in male and ovariectomized, while it has no effects on intact females. 2-Methoxyestradiol appears to be a promising pharmacological agent capable of improving endothelial function in men and postmenopausal women. PMID- 20302967 TI - Inhibition by ethyl pyruvate of the nuclear translocation of nuclear factor kappaB in cultured lung epithelial cells. AB - Tumor necrosis factor alpha (TNFalpha) is a cytokine inducing inflammatory responses. It has been reported that ethyl pyruvate has anti-inflammatory actions through inhibition of the transcription mediated by nuclear factor-kappa B (NF kappaB). By reporter gene assay, we first confirmed that TNFalpha activated the NF-kappaB pathway in cultured alveolar epithelial cells, A549 cells. This activation was strongly inhibited by ethyl pyruvate in a concentration-dependent manner. Treatment of the cells with TNFalpha-induced phosphorylation and degradation of IkappaBalpha within 15 min. The level of IkappaBalpha protein was increased from 30 min, suggesting an increase in the NF-kappaB-mediated transcription of IkappaBalpha. Ethyl pyruvate did not affect the changes in IkappaBalpha within 15 min, but strongly inhibited the increase in the IkappaBalpha protein level from 30 min. An immunoblot analysis revealed that ethyl pyruvate inhibited the nuclear translocation of RelA from 5 min of the treatment with TNFalpha. These results strongly suggested that ethyl pyruvate inhibited the NF-kappaB pathway through inhibition of the nuclear translocation of RelA. Ethyl pyruvate may be a good therapeutic drug for inflammation in which activation of the NF-kappaB pathway is involved. PMID- 20302968 TI - Identification of flux control in metabolic networks using non-equilibrium thermodynamics. AB - A method is presented to identify flux controlling reactions in metabolic networks using experimentally determined flux distributions. The method is based on the application of Ziegler's principle for the maximization of entropy production. According to this principle a metabolic network tends to maximize the entropy production rate while satisfying mass balances and maximal rate constraints. Experimental flux data corresponding to four different metabolic states of Saccharomyces cerevisiae were used to identify the corresponding flux controlling reactions. The bottleneck nature of several of the identified reactions was confirmed by earlier studies on over-expression of the identified target genes. The method also explains the failure of all the previous trials of increasing the glycolysis rate by direct over-expression of several glycolytic enzymes. These findings point to a wider use of the method for identification of novel targets for metabolic engineering of microorganisms used for sustainable production of fuels and chemicals. PMID- 20302969 TI - Preservatives in eyedrops: the good, the bad and the ugly. AB - There is a large body of evidence from experimental and clinical studies showing that the long-term use of topical drugs may induce ocular surface changes, causing ocular discomfort, tear film instability, conjunctival inflammation, subconjunctival fibrosis, epithelial apoptosis, corneal surface impairment, and the potential risk of failure for further glaucoma surgery. Subclinical inflammation has also been described in patients receiving antiglaucoma treatments for long periods of time. However, the mechanisms involved, i.e., allergic, toxic, or inflammatory, as well as the respective roles of the active compound and the preservative in inducing the toxic and/or proinflammatory effects of ophthalmic solutions, is still being debated. The most frequently used preservative, benzalkonium chloride (BAK), has consistently demonstrated its toxic effects in laboratory, experimental, and clinical studies. As a quaternary ammonium, this compound has been shown to cause tear film instability, loss of goblet cells, conjunctival squamous metaplasia and apoptosis, disruption of the corneal epithelium barrier, and damage to deeper ocular tissues. The mechanisms causing these effects have not been fully elucidated, although the involvement of immunoinflammatory reactions with the release of proinflammatory cytokines, apoptosis, oxidative stress, as well as direct interactions with the lipid components of the tear film and cell membranes have been well established. Preservative-induced adverse effects are therefore far from being restricted to only allergic reactions, and side effects are often very difficult to identify because they mostly occur in a delayed or poorly specific manner. Care should therefore be taken to avoid the long-term use of preservatives, otherwise a less toxic alternative to BAK should be developed, as this weakly allergenic but highly toxic compound exerts dose- and time-dependent effects. On the basis of all these experimental and clinical reports, it would be advisable to use benzalkonium-free solutions whenever possible, especially in patients with the greatest exposure to high doses or prolonged treatments, in those suffering from preexisting or concomitant ocular surface diseases, and those experiencing side effects related to the ocular surface. Indeed, mild symptoms should not be underestimated, neglected, or denied, because they may very well be the apparent manifestations of more severe, potentially threatening subclinical reactions that may later cause major concerns. PMID- 20302970 TI - Regulation of angiogenesis by a small GTPase Rap1. AB - Small GTPase Rap1 has been extensively studied in vitro and shown to regulate multiple basic cellular processes. Until recently, the best studied aspect of Rap1 function in endothelial cells involved its role in regulation of cell-cell junction formation and remodeling. These in vitro studies have increased understanding of the molecular players regulating Rap1 activity, including mechanisms through which Rap1 regulates endothelial permeability. Several recent reports provide emerging evidence that Rap1 function in endothelial cells is not limited to promoting barrier but that it also regulates basic endothelial responses to angiogenic stimulation and that Rap1 may act as a positive regulator of angiogenesis in vivo. This article provides an overview of these findings in the context of the existing knowledge of the function of the two Rap1 isoforms, followed by speculation regarding potential mechanisms through which Rap1 proteins may be regulating angiogenesis. PMID- 20302971 TI - Cell adhesion glycoprotein vitronectin during Xenopus laevis embryogenesis. AB - Vitronectin (vn) is a cell-adhesive glycoprotein present in blood and extracellular matrix of all vertebrates. In the present study we reported the cDNA cloning of Xenopus laevisvitronectin and its spatial and temporal expression pattern during the embryonic development of this important model organism. The deduced amino acid sequence of Xenopus laevis vn showed 49%, 47% and 43% identity with human, chicken and zebrafish orthologs, respectively, whereas the comparison with Xenopus tropicalis vn presented 85% identity. The structural organization consisting of a somatomedin B domain and two hemopexin-like domains was similar to higher vertebrate vitronectins. The vn transcripts were detected from stage 28 onward. At tadpole stages, vn is expressed in heart, gut derivatives and in the notochord. The protein was detected in heart, liver, foregut, pronephros and notochord at stages 43 and 47 of Xenopus embryos. Our results suggest that vitronectin is developmentally regulated and could participate in embryo organogenesis. PMID- 20302972 TI - Conserved sequence of the TgsGP gene in Group 1 Trypanosoma brucei gambiense. AB - The trypanosome responsible for the majority of cases of human trypanosomiasis in Africa is Group 1 Trypanosoma brucei gambiense. Currently the most reliable test for the parasite is based on a single gene, which encodes a 47kDa receptor-like T. b. gambiense-specific glycoprotein, TgsGP, expressed in the flagellar pocket of bloodstream forms. Although TgsGP has been demonstrated in T. b. gambiense throughout its geographic range, similar genes have been demonstrated in other T. brucei sspp. isolates, and there are no data on the extent of sequence variation in TgsGP. Here we have carried out a comparison of TgsGP sequences in a range of Group 1 T. b. gambiense isolates and compared the gene to homologues in other T. brucei sspp. in order to provide information to support the use of this gene as the key identification target for Group 1 T. b. gambiense. We demonstrate that the sequence of TgsGP is well conserved in Group 1 T. b. gambiense across the endemic range of gambian human trypanosomiasis and confirm that this gene is a suitable target for specific detection of this parasite. The TgsGp-like genes in some isolates of T. b. brucei, T. b. rhodesiense and Group 2 T. b. gambiense are closely similar to VSG Tb10.v4.0178, which may be the ancestral gene from which TgsGP was derived. PMID- 20302973 TI - Genetic characterization of Indian type O FMD virus 3A region in context with host cell preference. AB - The 3A region of foot-and-mouth disease virus has been implicated in host range and virulence. For example, amino acid deletions in the porcinophilic strain (O/TAW/97) at 93-102aa of the 153 codons long 3A protein have been recognized as the determinant of species specificity. In the present study, 18 type O FMDV isolates from India were adapted in different cell culture systems and the 3A sequence was analyzed. These isolates had complete 3A coding sequence (153aa) and did not exhibit growth restriction in cells based on species of origin. The 3A region was found to be highly conserved at N-terminal half (1-75aa) but exhibited variability or substitutions towards C-terminal region (80-153). Moreover the amino acid substitutions were more frequent in recent Indian buffalo isolates but none of the Indian isolates showed deletion in 3A protein, which may be the reason for the absence of host specificity in vitro. Further inclusive analysis of 3A region will reveal interesting facts about the variability of FMD virus 3A region in an endemic environment. PMID- 20302974 TI - Should patients be screened for 12S rRNA mutations before treatment with aminoglycosides? PMID- 20302975 TI - Structure of a premicellar complex of alkyl sulfates with the interfacial binding surfaces of four subunits of phospholipase A2. AB - The properties of three discrete premicellar complexes (E1#, E2#, E3#) of pig pancreatic group-IB secreted phospholipase A2 (sPLA2) with monodisperse alkyl sulfates have been characterized [Berg, O. G. et al., Biochemistry 43, 7999-8013, 2004]. Here we have solved the 2.7 A crystal structure of group-IB sPLA2 complexed with 12 molecules of octyl sulfate (C8S) in a form consistent with a tetrameric oligomeric that exists during the E1# phase of premicellar complexes. The alkyl tails of the C8S molecules are centered in the middle of the tetrameric cluster of sPLA2 subunits. Three of the four sPLA2 subunits also contain a C8S molecule in the active site pocket. The sulfate oxygen of a C8S ligand is complexed to the active site calcium in three of the four protein active sites. The interactions of the alkyl sulfate head group with Arg-6 and Lys-10, as well as the backbone amide of Met-20, are analogous to those observed in the previously solved sPLA2 crystal structures with bound phosphate and sulfate anions. The cluster of three anions found in the present structure is postulated to be the site for nucleating the binding of anionic amphiphiles to the interfacial surface of the protein, and therefore this binding interaction has implications for interfacial activation of the enzyme. PMID- 20302976 TI - Vascular differentiation of bone marrow stem cells is directed by a tunable three dimensional matrix. AB - Microenvironmental cues are critical in regulating cell behavior and fate. The roles that matrix mechanical signals play in regulating cell behavior have recently been elucidated. An artificial matrix that can maintain the appropriate characteristics for transplanted stem cells is therefore needed to achieve a desired cell phenotype. The objective of this study was to develop a three dimensional (3-D) matrix with tunable physical and mechanical properties and investigate their effects on mesenchymal stem cell (MSC) differentiation towards vascular cell types. In this study we developed an extracellular microenvironment by modifying fibrinogen with various polyethylene glycol (PEG) derivatives. We hypothesized that adjusting the type of PEG derivative to modify the resultant physical and mechanical characteristics of fibrin would allow us to create a tunable system for use in culture or in vivo in conjunction with a regenerative medicine strategy. Human MSC (hMSC) were entrapped into PEGylated fibrin matrices at a density of 50,000 cells ml(-1). Cell phenotypes were confirmed by immunofluorescent staining as well as the use of oligonucleotide arrays. Vascular phenotypes were correlated with measured mechanical properties and fiber diameters of the PEGylated fibrin matrices. Blocking studies were performed to identify mechanistic factors controlling MSC differentiation through selected blocking of matrix degradation or cell contraction. Cell-matrix interactions were also examined in vivo. Our results demonstrate that transdifferentiation of MSC towards an endothelial cell phenotype is profoundly affected by the 3-D matrix microenvironment. Our work provides a predictive road map for the creation of fibrin-based matrices that support robust endothelial cell gene expression and tubulogenesis. PMID- 20302977 TI - Effects of a surface topography composite with puerariae radix on human STRO-1 positive stem cells. AB - Human skeletal stem cells (STRO-1 positive/STRO-1+) respond to different topographical features in various ways. On a flat surface these cells spread and tend to develop a fibroblast-like morphology. On a microgrooved surface enriched skeletal stem cell populations prefer to stretch along the grooves, which affects their cellular structure and differentiation, a phenomenon known as contact guidance. Growth factors, hormones and chemicals can also stimulate cell differentiation. A traditional Chinese medicine, puerariae radix, has previously been observed to stimulate bone formation. The active ingredients have been identified as isoflavones with estrogen-like bioactivity. This study combined the effects of microgrooved topology and hormone-like isoflavones in the biodegradable polymer polycaprolactone (PCL). Human osteogenic cells (STRO-1+) were cultured on flat PCL, grooved PCL and puerariae powder-impregnated grooved PCL for 5 weeks. Coomassie staining indicated that cell growth and survival was similar on flat PCL, grooved PCL and grooved PCL impregnated with 1 wt.% or 2 wt.% puerariae powder. Grooved PCL impregnated with 2 wt.% puerariae powder was observed to have an influence on protein expression, as observed by positive osteocalcin staining. Protein expression profiles were analyzed by difference gel electrophoresis to identify proteins that showed modulation of expression in response to these different environments. Overall, our results suggest that puerariae powder has an additive effect, along with microgrooved topographical stimulation, to promote changes in the STRO-1+ proteome that affect cell phenotype. PMID- 20302978 TI - Pain after surgery: can protective analgesia reduce pain? A randomised clinical trial. AB - AIM: To improve the patients postoperative pain experience using protective analgesia for patients undergoing third molar surgery under day case general anaesthesia. MATERIAL AND METHODS: Patients were randomly allocated to a protective analgesia (1.6g modified release ibuprofen) or conventional analgesia (400mg conventional ibuprofen) orally 2h preoperatively. Surgical model was third molar surgery. Postoperative outcomes of interest were pain intensity at 30 min, 1, 6, 24 and 48 h. The time to rescue analgesia, overall assessment of pain control, safety and tolerability profiles were also recorded. RESULTS: 122 patients entered the study providing 98 evaluable patients for analysis. Patients in the protective analgesia group reported more pain than those in the conventional group at 30 min, 1, 6 and 48 h following surgery, although this difference was only statistically significant at the 30 min time point. 62.2% of patients required rescue analgesia within 6h after surgery. The median time for patients who had to take rescue analgesia was 3.1h. Patients in the protective analgesia group reported a longer time to rescue analgesia compared with those in conventional analgesia group. Overall, 91.7% of patients were at least satisfied with their pain control. CONCLUSION: There was no difference in the protective analgesia group compared with conventional analgesia group in improving postoperative pain experience. A different protective analgesia regime may be necessary, which employs a more aggressive and multimodal strategy for postoperative pain management. PMID- 20302979 TI - Investigation of gene dosage imbalances in patients with Noonan syndrome using multiplex ligation-dependent probe amplification analysis. AB - The RAS-MAPK syndromes are a group of clinically and genetically related disorders caused by dysregulation of the RAS-MAPK pathway. A member of this group of disorders, Noonan syndrome (NS), is associated with several different genes within the RAS-MAPK pathway. To date, mutations in PTPN11, SOS1, KRAS, RAF1 and SHOC2 are known to cause NS and a small group of patients harbour mutations in BRAF, MEK1 or NRAS. The majority of the mutations are predicted to cause an up regulation of the pathway; hence they are gain-of-function mutations. Despite recent advances in gene identification in NS, the genetic aetiology is still unknown in about 1/4 of patients. To investigate the contribution of gene dosage imbalances of RAS-MAPK-related genes to the pathogenesis of NS, a multiplex ligation-dependent probe amplification (MLPA) assay was developed. Two probe sets were designed for seven RAS-MAPK-syndrome-related candidate genes: PTPN11, SOS1, RAF1, KRAS, BRAF, MEK1 and MEK2. The probe sets were validated in 15 healthy control individuals and in glioma tumour cell lines. Subsequently, 44 NS patients negative for mutations in known NS-associated genes were screened using the two probe sets. The MLPA results for the patients revealed no gene dosage imbalances. In conclusion, the present results exclude copy number variation of PTPN11, SOS1, RAF1, KRAS, BRAF, MEK1 and MEK2 as a common pathogenic mechanism of NS. The validated and optimised RAS-MAPK probe sets presented here enable rapid high throughput screening of further patients with RAS-MAPK syndromes. PMID- 20302980 TI - Sperm FISH analysis in two healthy infertile brothers with t(15;18) unbalanced translocation: Implications for genetic counselling and reproductive management. AB - Numerous studies have shown that balanced reciprocal or Robertsonian translocations and inversions are associated with reduced or absent sperm production. In contrast, a similar association has been rarely reported for unbalanced translocations. An unbalanced translocation, 45,XY, 15,der(18)t(15;18)(q11.2;q23), was found in two healthy infertile brothers who were referred to our hospital together with their partners for infertility. At least two routine semen analyses and karyotyping were done for each of the brothers. Sperm meiotic segregation was studied for both with a three-color FISH assay using locus-specific probes. Semen analyses showed a severe oligo-astheno teratozoospermia with remarkably similar profiles in the two brothers. The unbalanced translocation had a deletion of 15pter-15q11.2 as well as a deletion of 18q23-18qter. The meiotic segregation was similar in the two brothers with a prevalence of alternate segregation mode. However, no phenotypic effect in the offspring can be expected only if the normal chromosomes 15 and 18 are transmitted to progeny. According to the sperm FISH results, the theoretical probability of this happening is about 25%. Based on the overall results, genetic and reproductive counselling was offered to both couples. Finally, both couples chose the alternative of donor insemination rather than preimplantation genetic diagnosis. The present study helps delineating a phenotypically silent CNV at the distal part of chromosome 18 long arm and illustrates the advantages of an integrated multidisciplinary genetic, reproductive and psychological approach to give the best possible assistance to couples who are faced with a complex and distressing genetic cause of infertility. PMID- 20302981 TI - Arterial steal in brachiocephalic arteriovenous fistula: could it be prevented? PMID- 20302982 TI - Depression in hospitalized and stable heart failure patients in an urban Nigerian teaching hospital: a cautionary comment. PMID- 20302983 TI - Psychiatric manifestations in systemic lupus erythematosus mimic psychotic prodrome: a case report. PMID- 20302985 TI - Correlates of symptoms of depression and anxiety in chronic hemodialysis patients. AB - OBJECTIVE: Little is known about the demographic, clinical and laboratory variables which may be correlated with symptoms of depression and anxiety in hemodialysis (HD) patients. The present study aimed at evaluating such correlation in HD patients treated at a single HD center in a Mediterranean country. METHODS: Eighty HD patients were assessed for depression and anxiety with the Beck Depression Inventory (BDI) and the Hamilton Anxiety Rating Scale (HARS). The scores of BDI and HARS were correlated with demographic, clinical and laboratory variables. RESULTS: Based on the Beck Depression Inventory, 38 patients had no symptoms of depression and 42 had symptoms of depression. Based on the HARS, three patients had no symptoms of anxiety and 38 had mild symptoms of anxiety, whereas moderate or severe symptoms of anxiety were present in 39 patients. In univariate analysis, BDI score correlated significantly with age, the Charlson Comorbidity Index, SF-36 Vitality Subscale, Mini-Mental Status Examination, creatinine, albumin, plasma 25-hydroxy vitamin D and interleukin-6 (IL-6) levels. HARS score correlated significantly with age, Charlson Comorbidity Index, SF-36 Vitality Subscale and parathyroid hormone (PTH) levels. In the multivariate analysis, a direct and an inverse correlation between BDI and IL-6 [P=.042, OR=1.31 (95% CI=1.01-1.71)] and creatinine [P=.050, OR=0.73 (95% CI=0.54 1.00)] was observed. With regard to HARS, only a direct correlation with Charlson Comorbidity Index [P<.001, OR=1.55 (95% CI=1.22-1.96)] was found. CONCLUSION: Although numerous demographic, clinical and laboratory variables correlated with BDI and HARS in univariate analysis, the multivariate regression analysis showed only a direct correlation between BDI and IL-6 [P=.042, OR=1.31 (95% CI=1.01 1.71)] and an inverse correlation between BDI and creatinine [P=.050, OR=0.73 (95% CI=0.54-1.00)] and a direct correlation between HARS and the Charlson Comorbidity Index [P<.001, OR=1.55 (95% CI=1.22-1.96)]. PMID- 20302986 TI - Do mental disorders and eating patterns affect long-term weight loss maintenance? AB - OBJECTIVE: This study aimed to assess the impact of mental disorders on weight loss maintenance among initially successful weight losers who participated in a very-low-calorie diet program. METHOD: A total of 251 obese individuals were assessed in a prospective longitudinal study over a period of 4 years. Mental disorders and eating patterns were assessed by structured interviews at baseline and by standardized questionnaires at baseline (T(1)), after 1 year (T(2)) and on 3-year follow-up (T(3)). Analyses were performed with an intention-to-treat method. RESULTS: Based on the intention-to-treat sample, 166 successful weight losers at T(2) (weight loss > or = 10%) were identified. Of those, 47 (28.3%) maintained a weight loss of > or = 5% of their pretreatment weight, whereas 119 (71.7%) maintained a loss of less than 5% of their pretreatment weight at T(3). History of substance abuse/dependence disorder and grazing prior to treatment increased the likelihood of successful weight loss maintenance. High levels of cognitive control, low levels of disinhibition on 3-year follow-up and initial body mass index also were associated with successful weight loss maintenance. CONCLUSION: Strategies that helped individuals overcome earlier mental disorders might help to establish better self-regulation and maintain high cognitive control of eating and subsequently increase the possibility of maintaining weight loss in the long run. PMID- 20302984 TI - Association of major depression and mortality in Stage 5 diabetic chronic kidney disease. AB - OBJECTIVES: Depression is the most common psychiatric disorder in patients with chronic kidney disease (CKD). We sought to determine the association of major depression with mortality among diabetic patients with late stage CKD. METHOD: The Pathways Study is a longitudinal, prospective cohort study initiated to determine the impact of depression on outcomes among primary care diabetic patients. Subjects were followed from 2001 until 2007 for a mean duration of 4.4 years. Major depression, identified by the Patient Health Questionnaire-9, was the primary exposure of interest. Stage 5 CKD was determined by dialysis codes and estimated glomerular filtration rate (<15 ml/min). An adjusted Cox proportional hazards multivariable model was used to determine the association of baseline major depression with mortality. RESULTS: Of the 4128 enrolled subjects, 110 were identified with stage 5 CKD at baseline. Of those, 34 (22.1%) had major depression. Over a period of 5 years, major depression was associated with 2.95 fold greater risk of death (95% CI=1.24-7.02) compared to those with no or few depressive symptoms. CONCLUSION: Major depression at baseline was associated with a 2.95-fold greater risk of mortality among stage 5 CKD diabetic patients. Given the high mortality risk, further testing of targeted depression interventions should be considered in this population. PMID- 20302987 TI - Quality of end-of-life care for dementia patients during acute hospital admission: a retrospective study in Ireland. AB - OBJECTIVES: To examine the quality of end-of-life care received by patients with and without dementia on acute medical wards during their final hospitalization. METHODS: A retrospective clinical case note review of patients aged over 65 who had died on acute medical wards within a 6-month period in a general hospital in Dublin was conducted. Seventy-five multidisciplinary clinical notes were available for scrutiny in order to identify cognitive status, measure the frequency of invasive procedures undertaken and examine the quality of palliative care as benchmarked with the Liverpool Care Pathway for the Dying Patient (LCP) program. Comparison between patients with and without dementia was made. RESULTS: Eighteen (24.0%) subjects had dementia, 32 (42.7%) subjects were described as "cognitively intact" and 25 subjects did not have reference to cognitive status. Of the 50 patients with known cognitive status, 27 (54.0%) had had a Mini Mental State Examination (MMSE) conducted (10 dementia vs. 17 nondementia). Patients were equally subjected to invasive interventions regardless of their cognitive status. However, dementia patients were significantly less likely to be referred to palliative care interventions (P=.007), to be prescribed palliative drugs (P=.017) and to have carers involved in decision making (P=.006). CONCLUSION: Individuals with dementia may be receiving different end-of-life care from those without. The effective delivery of robust multidisciplinary frameworks for the palliation of symptoms of hospitalized dementia patients remains an important clinical goal. PMID- 20302988 TI - Risk factors for depression and anxiety in survivors of acute respiratory distress syndrome. AB - OBJECTIVE: Depression and anxiety are common morbidities of critical illness. We assessed risk factors of depression and anxiety in Acute Respiratory Distress Syndrome (ARDS) survivors at 1 and 2 years post-hospital discharge. METHOD: Risk factors for depression and anxiety at 1 and 2 years were assessed using stepwise multiple regression analyses, with and without 1-year outcomes. RESULTS: ARDS survivors had depression (16% and 23%) and anxiety (24% and 23%) at 1 and 2 years, respectively. Predictors of depression at 1 year were alcohol dependence, female gender and younger age (P=.006). Predictors of anxiety were ratio of arterial oxygen tension to inspired oxygen fraction and duration of mechanical ventilation (P<.005). Predictors of depression at 2 years were depression at 1 year and the presence of cognitive sequelae (P<.0001). Predictors of anxiety at 2 years was anxiety at 1 year (P<.0001). CONCLUSIONS: Medical variables that predicted depression or anxiety at 1 year no longer predicted depression and anxiety at 2 years. Medical variables appear to have a short-term effect on psychiatric outcomes. At 2 years lifestyle behaviors including history of smoking along with cognitive sequelae, depression and anxiety at 1 year predict depression and anxiety. PMID- 20302989 TI - Hospital admissions due to physical disease in people with schizophrenia: a national population-based study. AB - OBJECTIVES: To examine nonpsychiatric hospitalizations in people with schizophrenia and to describe the epidemiological features of these admissions. METHODS: We analyzed the 2000-2004 Spanish National Hospital Discharge Registry, identified records coded for schizophrenia (295.xx), selected admissions due to non-psychiatric causes and characterized the physical diseases using the International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) system and the Deyo-Charlson Index. RESULTS: From all 2000-2004 hospitalizations in subjects with schizophrenia, 21 484 records (34%) were eligible for analysis. The mean age was 53 years, 61% were men. The mean number of ICD-9-CM codes was 2.3. The main diagnoses at discharge were injury-poisoning (19%) and respiratory (15%), digestive (14%) and circulatory diseases (12%), but there were significant age and gender-related differences. Inhospital mortality was 6.9% and the mean age of death was 63 years. Circulatory, respiratory diseases and neoplasms accounted for 21%, 18% and 17% of deaths, respectively. Inhospital mortality significantly correlated with age, the Deyo-Charlson Index and some specific processes. CONCLUSIONS: Hospitalizations due to physical disease are frequent among people with schizophrenia and associated with a substantial burden and in-hospital mortality in Spain. This information may prove useful for the design and application of preventive and therapeutic programs in the early and silent phases of the most prevalent physical diseases. PMID- 20302990 TI - Prevalence of idiopathic and secondary restless legs syndrome in Korean Women. AB - OBJECTIVE: The aim of this study was to identify the prevalence of idiopathic and secondary restless legs syndrome (RLS) and to compare them among Korean women. METHODS: A total of 1000 women aged 40-69 years from the general population were included in the study. The questionnaire used to gather data included modified International Restless Legs Syndrome Study Group (IRLSSG) criteria, and questions related to RLS. RESULTS: Of the entire cohort, 65 subjects were diagnosed as having RLS according to IRLSSG criteria. The overall prevalence of RLS was thus 6.5%. Of those subjects with symptoms of RLS, 81.5% complained of insomnia. The age at the onset of RLS was 38.9 +/- 8.6 years. RLS symptoms were experienced every day by 18.5% of affected subjects. None of the RLS subjects revealed in this study had previously been diagnosed or treated for their RLS problems. CONCLUSION: The prevalence of RLS reported herein is low compared with that reported for Western countries. Our study provides further evidence for low prevalence of RLS in Asian populations and supports the view that RLS is poorly recognized by both physicians and the general population, resulting in suboptimal management of the disorder. PMID- 20302991 TI - Increased fear of progression in cancer patients with recurrence. AB - OBJECTIVE: This study investigated the fear of progression (FoP) in cancer patients and the discriminant ability of the Fear of Progression Questionnaire (FoP-Q) against the Hospital Anxiety and Depression Scale (HADS), while also examining relationships between FoP, satisfaction outcomes and supportive needs. METHOD: The FoP-Q and HADS were administered to 112 cancer patients in Korea during June and July 2006. The FoP-Q totals and subscales, and the HADS scores were compared across three groups (patients with recurrence, patients with metastases and controls experiencing neither). RESULTS: Comparison of the FoP-Q total score to HADS anxiety (HADS-A) and depression (HADS-D) scores showed higher FoP in the recurrence group compared to the control group (P=.009). Subscale score comparisons revealed a heightened "affective reaction" (P=.003) to cancer progression and fear of "loss of autonomy" (P=.011) in recurrence patients. FoP-Q score showed a moderate association with HADS-A (r=.54, P=.000) and a significant association with treatment satisfaction (r=-.26, P=.007), medical staff and communication (r=-.31, P=.001), and supportive needs (r=.41, P=.000). CONCLUSION: The importance of providing supportive interventions tailored to the specific emotional concerns of cancer patients, assessed via appropriate, disease-specific instruments, and the need to pay special attention to the concerns of recurrence patients are suggested. PMID- 20302992 TI - Incidence and correlates of delirium in a West African mental health clinic. AB - OBJECTIVE: To determine the incidence of delirium in those patients presenting to a psychiatric clinic in Nigeria and to examine if any demographic or clinical variables were correlated with this diagnosis. METHOD: A prospective survey design; 264 consecutive new referrals to a psychiatric clinic in Nigeria were assessed for the presence of delirium using a standardised diagnostic scale. Data was analysed for normality and appropriate statistical test employed to examine the relationships between the presence of delirium and demographic and clinical variables. RESULTS: Of individuals presenting to the mental health clinics, 18.2% had delirium. No demographic variable was significant regarding the presence or absence of delirium. With regard to clinical variables duration of current symptoms, referral source and the presence of comorbid physical illness were significantly associated with the presence of delirium. Most delirium was due to infections. Nearly all patients with delirium were prescribed psychotropic medication (95.2%), and most attributed their symptoms to a spiritual cause. CONCLUSION(S): Delirium presents more commonly to psychiatry services in the less developed world compared to the West. Development efforts should focus on recognition and management of delirium to improve outcomes and maximise resources. PMID- 20302993 TI - Addressing stigma of depression in Latino primary care patients. AB - OBJECTIVES: To develop a validated stigma checklist to assist physicians in addressing depression in Latino patients. METHOD: Two hundred low-income, Spanish speaking, Latino patients in primary care clinics were screened for depression using Patient Health Questionnaires (PHQ-2 and PHQ-9), and medical records were reviewed. With the use of a wide pool of stigma items, empirical methods were used to develop a stigma checklist from this primary care sample and patient information was used to demonstrate construct validity. RESULTS: Patients reporting higher levels of perceived stigma using the stigma checklist were less likely to disclose their depression diagnosis to their family and friends (P<.05) and also less likely to be taking depression medication (OR=.78; 95% CI, .62 .99). Patients with stigma were less likely to be able to manage their depression (OR=.79; 95% CI, .65-.96) and more likely to have missed scheduled appointment visits (OR=1.44; 95% CI, 1.03-2.02). CONCLUSION: Given the strong relationship between stigma and care of depression, primary care clinicians should be aware of and address stigma among their depressed Latino patients. The stigma checklist presented for treating Spanish-speaking Latino patients in primary care may be used to assess depressed patients for stigma to help inform clinical management of patients. PMID- 20302994 TI - Prevalence and rates of recognition of anxiety disorders in internal medicine outpatient departments of 23 general hospitals in Shenyang, China. AB - OBJECTIVE: Assess the prevalence, risk factors and treating clinicians' rates of recognition of anxiety disorders in internal medicine departments of different types of general hospitals in Shenyang, China. METHOD: A two-stage screening process using an expanded Chinese version of the 12-item General Health Questionnaire (GHQ) and the Structured Clinical Interview for DSM-IV-TR Axis I Disorders (SCID) identified 457 persons 15 years of age or older with current anxiety disorders from among 5312 consecutive attendees at the outpatient internal medicine departments of 23 randomly selected general hospitals. Clinical charts were reviewed to determine whether or not the treating internist had made a diagnosis of anxiety or prescribed anxiolytic medications. RESULTS: The 1-month prevalence of any type of anxiety disorder was 9.8% (95% CI=9.0-10.8%). The prevalences of the three most common disorders: anxiety disorder not otherwise specified, generalized anxiety disorder and anxiety disorder due to a general medical condition, were 6.3% (5.6-7.1%), 2.4% (2.0-2.9%), and 0.6% (0.4-0.8%), respectively. Multivariate logistic regression analysis identified the following independent predictors of having a current anxiety disorder: every being married (OR=3.5, 95% CI=2.3-5.4), prior treatment for psychological problems (3.3, 1.8 6.0), having religious beliefs (1.9, 1.3-2.9), low family income (1.5, 1.2-1.9) and never having attended college (1.3, 1.02-1.8). Among the 402 patients with anxiety disorders for whom the clinical chart was reviewed only 16 (4.0%, CI=2.3 6.3%) were diagnosed with an anxiety condition or treated with anxiolytic medications. CONCLUSION: The prevalence of anxiety in internal medicine outpatients in urban China is lower than that reported in most western countries and the profile of risk factors is somewhat different. The very low rate of recognition of these disorders by internists is related both to the low rates of care-seeking for psychological problems in the general population and to the high volume collective model of care delivery in the outpatient departments of Chinese general hospitals. Steps to increase the recognition and treatment of anxiety disorders in Chinese general hospitals must focus both on changing attitudes of patients and clinicians and, more importantly, on altering the structure of care delivery. PMID- 20302995 TI - Is major depression adequately diagnosed and treated by general practitioners? Results from an epidemiological study. AB - OBJECTIVES: The aim of this study was to (1) to explore the validity of the depression diagnosis made by the general practitioner (GP) and factors associated with it, (2) to estimate rates of treatment adequacy for depression and factors associated with it and (3) to study how rates of treatment adequacy vary when using different assessment methods and criteria. METHODS: Epidemiological survey carried out in 77 primary care centres representative of Catalonia. A total of 3815 patients were assessed. RESULTS: GPs identified 69 out of the 339 individuals who were diagnosed with a major depressive episode according to the Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-I) (sensitivity 0.22; kappa value: 0.16). The presence of emotional problems as the patients' primary complaint was associated with an increased probability of recognition. Rates of adequacy differed according to criteria: in the cases detected with the SCID-I interview, adequacy was 39.35% when using only patient self-reported data and 54.91% when taking into account data from the clinical chart. Rates of adequacy were higher when assessing adequacy among those considered depressed by the GP. CONCLUSION: GPs adequately treat most of those whom they consider to be depressed. However, they fail to recognise depressed patients when compared to a psychiatric gold standard. Rates of treatment adequacy varied widely depending on the method used to assess them. PMID- 20302996 TI - Iatrogenic delusional parasitosis: a case of physician-patient folie a deux. AB - This report presents a patient incorrectly diagnosed first with parasitic infestation and then with primary delusional parasitosis (DP). Neither diagnosis was correct. As she traveled from doctor to doctor, however, the primary DP label gained credibility via repetition, with her ongoing symptoms seen as proof of its truth. PMID- 20302997 TI - Is pregnancy associated with mood and anxiety disorders? A cross-sectional study. AB - OBJECTIVE: To compare current prevalence of mood and anxiety disorders in pregnant and nonpregnant women. METHOD: The study sample included 309 pregnant women and 107 control subjects. Mood and anxiety disorders were determined by structured clinical interviews. RESULTS: The rate of any mood or anxiety disorder was 19.4% in the pregnant women. Major depression (5.5%) and obsessive-compulsive disorder (5.2%) were the most common diagnoses in the pregnant women. There was no significant difference between pregnant and nonpregnant women with respect to the prevalence rate of mood and anxiety disorders. CONCLUSION: The results suggest that pregnancy is not a risk factor for the development of mood and anxiety disorders. PMID- 20302998 TI - Bupropion, a brief history of seizure risk. PMID- 20302999 TI - Screening for suicidality in cancer patients using Item 9 of the nine-item patient health questionnaire; does the item score predict who requires further assessment? AB - OBJECTIVE: To determine whether a higher score on Item 9 of the Patient Health Questionnaire-9 (range zero to three) was more likely to indicate suicidality as determined at subsequent clinical interview in cancer outpatients. METHOD: Analysis of anonymized data (with ethical approval) obtained from the routine clinical administration of self-report questionnaires and telephone interviews to patients attending a cancer centre in the UK. RESULTS: Complete data were available on 330 patients. Those with higher scores on the item were more likely to be suicidal at interview. However, a substantial number of those (54/235; 23%) who scored only one on the item were also found to be suicidal. CONCLUSIONS: A higher score on Item 9 of the PHQ-9 indicates a greater likelihood that the patient is suicidal. However, even patients who score only 1 may be suicidal and consequently also require further assessment. PMID- 20303000 TI - The successful treatment of disinhibition due to a possible case of non-human immunodeficiency virus neurosyphilis: a proposed pathophysiological explanation of the symptoms and treatment. AB - The psychiatric presentation of advanced neurosyphilis is well documented, yet there is no set protocol to treat these occurrences. This report indexes a 61 year-old African-American male with no known psychiatric history but with a pertinent medical history of neurosyphilis (non-human immunodeficiency virus). He developed an acute episode of disinhibition involving violence and poor executive judgment. The authors' propose that this patient's symptoms of disinhibition may have resulted from syphilitic invasion of frontal-subcortical structures, resulting in either top-down or bottom-up dysregulation and deterioration of social behavior. His episode resolved with administration of monotherapy carbamazepine. PMID- 20303001 TI - Psychiatric manifestations preceding fetal death in antiphospholipid syndrome. AB - OBJECTIVES: Antiphosholipid syndrome (APS) is a systemic autoimmune disorder characterized by a combination of thrombotic events, pregnancy morbidity and antiphospholipid antibodies. The objective of this report is to sensitize mental health professionals to the psychiatric manifestations of APS during pregnancy. To our knowledge, this is the first report on this matter. CASE SUMMARY: A 34 year-old pregnant woman, with no previous medical, obstetrical or psychiatric history, at the 18th week of pregnancy, acutely developed depressed mood, feelings of anxiety and insomnia with a strong premonition that "the fetus would die." Actual fetal loss ensued a few days later. During induced labor, the patient had an agitated delirium. Symptoms of depression, slowed mentation and apprehension persisted for at least 2 months after fetal demise and required pharmacological treatment. APS diagnosis was established based on clinical events and persistent findings of antiphosholipid antibodies as well as multiple high density foci in the subcortical white matter of the frontal lobes in brain magnetic resonance imaging. CONCLUSIONS: Psychiatric symptomatology, as well as a premonitory sense of upcoming loss of pregnancy, preceded actual fetal loss and APS diagnosis in the presented case, indicating that psychiatric symptoms may present during pregnancy, perhaps as an early sign. PMID- 20303002 TI - Restless legs syndrome with carbamazepine-induced osteomalacia: causal or casual association. AB - Restless legs syndrome (RLS) is a sensorimotor sleep-related disorder which can be idiopathic or secondary. Secondary RLS is associated with a variety of conditions. Here we report a 16-year-old girl with RLS secondary to vitamin D deficiency (VDD) caused by chronic administration of carbamazepine. We also speculate on the possible mechanisms for the development of RLS in patient with VDD. PMID- 20303003 TI - A presumed case of phantom limb pain treated successfully with duloxetine and pregabalin. AB - Phantom limb pain (PLP) may occur in nearly 80% of amputation patients. Current research has highlighted several changes that occur in the nociception pathway post amputation. With this knowledge, novel therapies were found that could decrease PLP. Two such drugs are duloxetine and pregabalin, each effecting unique steps in the nociception pathway. We also review the neurobiology and efficacy of this treatment strategy. PMID- 20303004 TI - Marfan syndrome and schizophrenia: a case report and literature review. AB - INTRODUCTION: Marfan Syndrome (MFS), a disease of microfibril dysfunction, has been associated with schizophrenia in multiple case reports. CASE REPORT: We present one case and review the literature that suggests these conditions may share a common etiologic pathway. DISCUSSION: A possible underlying mechanism of both schizophrenia and MFS is the abnormal expression of growth factors and signaling cascades. CONCLUSION: MFS patients should be monitored for psychiatric symptoms and patients with signs of MFS should be referred for appropriate medical care. Also, by understanding shared mechanisms, we may develop better understanding and treatments. PMID- 20303006 TI - "Hospital length of stay for children and adolescents diagnosed with depression: is primary payer an influencing factor?" by Sclar et al. PMID- 20303008 TI - VEGFA +936C>T polymorphism and cancer risk: a meta-analysis. AB - Vascular endothelial growth factor A (VEGF-A), a major driver of physiological and pathological angiogenesis, plays important roles in the etiology and metastasis of cancers. The +936C>T polymorphism in the 3'-untranslated region of the VEGFA gene has been implicated in cancer risk and is related to VEGF-A protein production; however, published data have been conflicting. To derive a more precise estimation of the relationship, a meta-analysis was performed of 13,293 cancer cases and 12,308 control subjects from 29 published case-control studies. Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated to assess the association between +936C>T polymorphism and cancer risk. The meta analysis indicated that individuals with the +936 T had increased risk of oral cancer (OR = 1.39, 95% CI = 1.03-1.88), although no association was found in the contrast of T versus C (OR = 1.00, 95% CI = 0.91-1.10) in the pooled analyses. This meta-analysis supports the idea that VEGFA + 936 T is associated with increased risk of oral cancer. To draw comprehensive and true conclusions, further prospective studies with larger numbers of participants worldwide are needed to examine associations between VEGFA + 936C>T polymorphism and cancer risk. PMID- 20303007 TI - Oligonucleotide array outperforms SNP array on formalin-fixed paraffin-embedded clinical samples. AB - Compromised quality of formalin-fixed paraffin-embedded (FFPE)-derived DNA has compounded the use of archival specimens for array-based genomic studies. Recent technological advances have led to first successes in this field; however, there is currently no general agreement on the most suitable platform for the array based analysis of FFPE DNA. In this study, FFPE and matched fresh-frozen (FF) specimens were separately analyzed with Affymetrix single nucleotide polymorphism (SNP) 6.0 and Agilent 4x44K oligonucleotide arrays to compare the genomic profiles from the two tissue sources and to assess the relative performance of the two platforms on FFPE material. Genomic DNA was extracted from matched FFPE FF pairs of normal intestinal epithelium from four patients and were applied to the SNP and oligonucleotide platforms according to the manufacturer-recommended protocols. On the Affymetrix platform, a substantial increase in apparent copy number alterations was observed in all FFPE tissues relative to their matched FF counterparts. In contrast, FFPE and matched FF genomic profiles obtained via the Agilent platform were very similar. Both the SNP and the oligonucleotide platform performed comparably on FF material. This study demonstrates that Agilent oligonucleotide array comparative genomic hybridization generates reliable results from FFPE extracted DNA, whereas the Affymetrix SNP-based array seems less suitable for the analysis of FFPE material. PMID- 20303009 TI - The A61G EGF polymorphism is associated with development of extraaxial nervous system tumors but not with overall survival. AB - Epidermal growth factor can activate several signaling pathways, leading to proliferation, differentiation, and tumorigenesis of epithelial tissues by binding with its receptor. The EGF protein is involved in nervous system development, and polymorphisms in the EGF gene on chromosome band 4q25 are associated with brain cancers. The purpose of this study was to investigate the association between the single-nucleotide polymorphism of EGF+61G/A and extraaxial brain tumors in a population of the southeast of Brazil. We analyzed the genotype distribution of this polymorphism in 90 patients and 100 healthy subjects, using the polymerase chain reaction-restriction fragment length polymorphism technique. Comparison of genotype distribution revealed a significant difference between patients and control subjects (P < 0.001). The variant genotypes of A/G and G/G were associated with a significant increase of the risk of tumor development, compared with the homozygote A/A (P < 0.0001). When the analyses were stratified, we observed that the genotype G/G was more frequent in female patients (P=0.021). The same genotype was observed more frequently in patients with low-grade tumors (P=0.001). Overall survival rates did not show statistically significant differences. Our data suggest that the EGF A61G polymorphism can be associated with susceptibility to development of these tumors. PMID- 20303010 TI - Association of angiotensin converting enzyme gene insertion/deletion polymorphism with lung cancer in Turkey. AB - Angiotensin-converting enzyme (ACE) plays an important role in the physiological control of blood pressure and inflammation. We investigated an insertion/deletion (I/D) polymorphism of the gene for ACE in relation to cardiovascular, cerebrovascular, neurodegenerative, and inflammatory diseases. The purpose of the present study was to investigate a possible association between lung cancer and insertion/deletion polymorphism of the ACE gene. A total of 125 patients with lung cancer and 165 control subjects were enrolled in the present study. ACE I/D genotypes were determined by polymerase chain reaction. Allelic frequencies and genotype distribution of the ACE I/D polymorphism in the patient group were significantly different from control subjects (ACE II genotype 29.6 vs. 17.6%, P = 0.011; ACE I allele 49.6 vs. 39.4%, P =0.009). Our data suggest that the ACE I/D polymorphism could be a risk factor for patients with lung cancer. PMID- 20303011 TI - Genomic alterations of chromosome region 11p as predictive marker by array comparative genomic hybridization in lung adenocarcinoma patients. AB - Array comparative genomic hybridization (aCGH) provides a method to quantitatively measure the changes of DNA copy number with an extremely high resolution and to map them directly onto the complete linear genome sequences. In this study, we used aCGH to compare genomic alterations in fresh-frozen lung cancer tissues of 21 adenocarcinomas (AdCCs) (11 early relapse and 10 nonrelapse) and identified genomic alterations that showed significant by different frequency between early relapse and nonrelapse AdCCs. Twelve clones were identified by the false discovery rate (FDR) test, and Kaplan-Meier analyses were selected as predictive markers. The significant gain clones were found in 11p (11p15.4, 11p15.1, and 11p13). When the cutoff value was 2, study of the association between candidate clones and relapse prediction revealed that early relapse and nonrelapse groups were most effectively separated. To further validate the gain of chromosome 11p region that was identified by array CGH, fluorescence in situ hybridization (FISH) was performed. To further confirm the results of aCGH, copy number changes of cancer-related candidate genes in AdCC patients were compared by real-time quantitative polymerase chain reaction. Array CGH and real-time quantitative polymerase chain reaction data were found to correspond to delineated DNA copy number changes. Genomic alterations of chromosome 11p region in AdCC patients were observed with aCGH, and a relapsable marker was identified in the nonrelapse group. This marker could be useful in stratifying patient groups according to likelihood of relapse for adjuvant treatment after surgical resection. PMID- 20303012 TI - KRAS and BRAF mutations in prostate carcinomas of Chinese patients. AB - Aberrance in the RAS/RAF/MEK/MAPK pathway is reportedly important in many tumor types, including prostate carcinoma. Continuous activation of the pathway can be caused by mutations of upstream targets such as KRAS and BRAF. However, rates of KRAS and BRAF mutations in prostate carcinoma are reported to vary in different populations. To date, there has been no such report in Chinese patients. In this study, we examined 121 samples of prostate carcinoma in Chinese subjects for mutations at codons 12 and 13 of KRAS and codon 600 of BRAF by means of the mutant-enriched polymerase chain reaction-coupled sequencing method. The identified KRAS and BRAF mutations were analyzed for association with tumor differentiation and clinical stage. The result showed that KRAS mutations were detected in 9.1% (11 of 121) of prostate carcinomas, while no BRAF mutation was found in any case studied. No association was found between KRAS mutation and clinicopathological characteristics of the tumors. Our study suggests that mutations of KRAS, not BRAF, may play a role in the pathogenesis of prostate carcinoma in Chinese patients. PMID- 20303013 TI - Glutathione-S-transferase genotypes influence the risk of chemotherapy-related toxicities and prognosis in Korean patients with diffuse large B-cell lymphoma. AB - Polymorphisms in detoxification enzymes of the glutathione S-transferase (GST) family are associated with treatment response, resistance, and drug-related toxicity, all of which affect final clinical outcome. In this study, we investigated the influence of the genetic polymorphisms GSTM1, GSTT1, and GSTP1 on treatment response in 94 Korean patients with de novo diffuse large B-cell lymphoma, who had received rituximab plus cyclophosphamide/doxorubicin/vincristine/prednisone (R-CHOP) as a front-line regimen. Deletions of the GSTM1 and GSTT1 genes were detected using a multiplex polymerase chain reaction technique, and the functional GSTP1 polymorphism, Ile(105)Val, was genotyped using the TaqMan assay. The treatment response rate did not differ according to GST polymorphisms. Patients with the GSTT1-null genotype, however, showed more frequent grade III-IV chemotherapy-related toxicities, including leukocytopenia [odds ratio (OR)=3.1; 95% confidence interval (95%CI), 1.2-8.0; P=0.025], fever (OR=5.3; 95% CI, 1.4-19.7; P=0.009), and mucositis (OR=4.6; 95% CI, 1.4-15.1; P=0.012). Patients with the GSTM1/T1 double-null genotype had more grade III-IV thrombocytopenia (OR=7.8; 95% CI, 1.5 41.1; P=0.002) compared to those with other genotypes. In male patients, the GSTM1/T1 double-null genotype was associated with a shorter event-free survival period (P=0.02). This study suggests that GSTT1 deletion may significantly increase the risk of drug-related toxicity after R-CHOP chemotherapy in patients with DLBCL, and is associated with worse prognosis in males. PMID- 20303014 TI - High chromosomal instability in brain metastases of colorectal carcinoma. AB - Information on structural chromosomal changes in brain metastases (BM) of colorectal carcinoma (CRC) is very limited. Therapeutic and diagnostic strategies to reduce the risk of BM have potential impact on cancer mortality. By using comparative genomic hybridization, the primary CRC of 11 patients and their corresponding 13 BM were analyzed. BM showed significantly more mean chromosomal aberrations than the primary CRC (13.6+/-2.1 vs. 7.9+/-1.9, P=0.03), significantly more chromosomal gains (7.2+/-0.9 vs. 3.5+/-0.9, P=0.01), and tended to have also more losses (6.1+/-1.4 vs. 4.0+/-1.1, P=0.29). Changes that occurred significantly more often in BM than in primary CRC were gains of 8q, 12p, 12q, and 20p, as well as losses of 5q. BM of CRC show a significantly higher chromosomal instability in comparison to primary tumors. The prevalently altered genomic regions in the metastases of this study are likely to harbor genes that play an important role in the genesis of brain-specific metastasis. PMID- 20303015 TI - Prognostic and predictive value of 16p12.1 and 16q22.1 copy number changes in human breast cancer. AB - The present study investigated DNA copy number changes mapping to the p and q arms of chromosome 16 in breast cancer with the goal to determine their potential in identifying breast cancer patients with poor prognosis. We identified the minimal overlapping regions on chromosome 16 that are commonly deleted and amplified in breast tumors. Fluorescence in situ hybridization was used to screen a custom-made breast carcinoma tissue microarray representing all tumor grades, in order to detect DNA copy number changes mapping to 16p12.1 and 16q22.1. We generated 16q/16p ratios for each patient and examined the correlation between DNA copy number alterations and the patients' clinical and pathological parameters. We observed lower q/p ratios in grade I invasive carcinomas, compared with grade III carcinomas, which consistently showed high q/p ratios (P < 0.0091 and 0.0075). In addition, age adjusted for grade analysis revealed that tumors from younger patients (<45 yr) had significantly higher q/p ratios, suggesting that in younger individuals those tumors might be more aggressive (P < 0.0001). The finding that higher q/p ratios occur in younger patients offers a tool to identify high-risk individuals most likely to proceed to high grade. PMID- 20303016 TI - Segmental amplification of MLL gene associated with high expression of AURKA and AURKB genes in a case of acute monoblastic leukemia with complex karyotype. AB - We report a case of acute monoblastic leukemia showing a jumping translocation with the MLL gene in a 17-year-old male. Classic cytogenetic and spectral karyotyping revealed a complex karyotype, and fluorescence in situ hybridization (FISH) demonstrated amplification of the MLL gene followed by translocation to chromosomes 15q, 17q, and 19q. In addition, molecular analyses showed a high expression of AURKA and AURKB genes. It is already known that overexpression of Aurora kinases is associated with chromosomal instability and poor prognosis. The formation of jumping translocations is a rare cytogenetic event and there is evidence pointing toward preferential involvement of the heterochromatin region of donor chromosomes and the telomere ends of recipient chromosomes. Jumping translocation with the MLL gene rearrangement is an uncommon phenomenon reported in leukemia cytogenetics. PMID- 20303017 TI - Translocation (6;13)(p21;q14.1) as a rare nonrandom cytogenetic abnormality in chronic lymphocytic leukemia. AB - Chronic lymphocytic leukemia (CLL) is associated with recurrent cytogenetic abnormalities that are important prognostic indicators and may influence treatment choices. Nonetheless, several chromosome abnormalities have not yet been completely determined, because of the low mitotic in vitro activity of B-CLL cells. Now, novel technologies such as stimulation of CLL cells with new B-cell mitogens have helped to overcome this problem. We present here a novel conventional and molecular cytogenetic study of a CLL patient with t(6;13)(p21;q14.1), a rare chromosomal aberration. The findings contribute to the identification of rare recurrent aberrations and of any prognostic effect in CLL that could be used for prognostic and therapeutic purposes. The present study demonstrates that t(6;13)(p21;q14.1) as a secondary event to the interstitial deletion in 13q14 region, resulting in the loss of RB1, is a rare but nonrandom abnormality in CLL, resistant to the current treatment CLL protocols with a rather favorable or intermediate prognosis but definitely not an adverse prognosis. Further studies in more CLL patients are required to delineate the prognostic value of t(6;13)(p21;q14.1) and to identify any candidate genes with potential role in the pathogenesis of the disease. PMID- 20303018 TI - Detection of cryptic and variant IGH-MYC rearrangements in high-grade non Hodgkin's lymphoma by fluorescence in situ hybridization: implications for cytogenetic testing. AB - In recent years it has become increasingly evident that MYC rearrangements are not confined to classical Burkitt lymphoma (BL), but also occur in diffuse large B-cell lymphoma (DLBCL) and in the new subtype, "B-cell lymphoma, unclassifiable, with features intermediate between DLBCL and BL" (BCLU), which was recently described in the 2008 revision of the World Health Organization classification. The accurate identification of MYC rearrangements in these three subtypes of high grade lymphoma is becoming increasingly critical both in terms of diagnosis of classical BL and in light of the prognostic implications in cases of DLBCL and BCLU. We describe three cases of high-grade lymphoma in which cryptic insertion events, resulting in clinically significant IGH-MYC rearrangements, were detectable using an IGH/MYC three-color, dual-fusion fluorescence in situ hybridization (FISH) probe set, but were not detected using break-apart MYC FISH probes, thus highlighting the limitations of using break-apart probes as a stand alone test, particularly with the increased use of interphase FISH analysis of formalin-fixed, paraffin-embedded tissue sections in the diagnostic work-up of these patients. PMID- 20303019 TI - Training standards and imaging: will these have any impact on turf wars affecting radiologists? PMID- 20303020 TI - Cardiac computed tomography: a team approach? PMID- 20303021 TI - Canadian Association of Radiologists / Canadian Cardiovascular Society consensus training standards for cardiac computed tomography. PMID- 20303022 TI - Answer to case of the month #161. Internal hernia through the foramen of Winslow. PMID- 20303023 TI - Answer to case of the month #162. Emphysematous infection of the liver parenchyma. PMID- 20303024 TI - An objection to the New England Journal of Medicine vertebroplasty articles. PMID- 20303025 TI - Impact of pain and symptom burden on the health-related quality of life of hemodialysis patients. AB - CONTEXT: Dialysis patients experience tremendous symptom burden and substantial impaired health-related quality of life (HRQL). OBJECTIVES: We determined the association between symptom burden and HRQL in 591 hemodialysis patients. METHODS: Patients completed the modified Edmonton Symptom Assessment System and the Kidney Dialysis Quality of Life Short Form at baseline and after six months. RESULTS: There were no demographic, serological, or dialysis-related predictors for either HRQL or symptom burden. Pain, tiredness, lack of well-being, and depression were the only independent predictors of mental HRQL, accounting for 42.5% of the variation in the baseline mental health composite (MHC). Pain, fatigue, lack of well-being, and shortness of breath were the only independent predictors of physical HRQL, accounting for 38.5% of the variation in the baseline physical health composite (PHC). After follow-up, only changes in depression, anxiety, tiredness, and lack of appetite were independently associated with a change in MHC score, accounting for 48.7% of the variability. Only changes in pain, tiredness, and lack of appetite were independently associated with a change in PHC, accounting for 44.6% of the variability in the final multivariate regression model. No change in biochemical parameters predicted a change in either the MHC or the PHC. CONCLUSION: Symptom burden in end-stage renal disease was substantial and had a tremendous negative impact on all aspects of hemodialysis patients' HRQL. These patients, therefore, would likely benefit from the institution of programs to reduce symptom burden. PMID- 20303026 TI - Reducing patient barriers to pain and fatigue management. AB - CONTEXT: Pain and fatigue are recognized as critical symptoms that impact the quality of life of cancer patients. The barriers to pain and fatigue relief have been classified into three categories: patient, professional, and system barriers. OBJECTIVES: The overall objective of this trial as to test the effects of the "Passport to Comfort" intervention on reducing barriers to pain and fatigue management for ambulatory care cancer patients. METHODS: This quasi experimental, comparative study uses a Phase 1 control group of usual care followed sequentially by a Phase 2 intervention group in which educational and system-change efforts were directed toward improved pain and fatigue management. A sample of 187 cancer patients with breast, lung, colon, or prostate cancers, and a pain and/or fatigue rating of 4 or more (moderate to severe), were recruited. Patients in the intervention group received four educational sessions on pain/fatigue assessment and management, whereas patients in the control group received usual care. Pain and fatigue barriers and patient knowledge were measured at baseline, one month, and three months post-accrual. RESULTS: Patients in the intervention group experienced significant improvements in pain and fatigue measures immediately postintervention, and these improvements were sustained over time. CONCLUSION: The "Passport to Comfort" intervention was effective in reducing patient barriers to pain and fatigue management as well as in increasing patient knowledge regarding pain and fatigue. This intervention demonstrates innovation by translating the evidence-based guidelines for pain and fatigue as developed by the National Comprehensive Cancer Network into practice. PMID- 20303027 TI - Got volunteers? Association of hospice use of volunteers with bereaved family members' overall rating of the quality of end-of-life care. AB - CONTEXT: Volunteers are a key component of hospice, and they are required by Medicare conditions of participation in the United States. Yet, little is known about the impact of volunteers in hospice. OBJECTIVES: The goal of this study was to characterize whether bereaved family members in hospice programs with increased use of volunteer hours per patient day report higher overall satisfaction with hospice services. METHODS: A secondary analysis of the 2006 Family Evaluation of Hospice Care data repository with hospice organization data regarding the number of volunteer hours in direct patient care and the total number of patient days served. A multivariate model examined the association of institutional rate of bereaved family members stating end-of-life care was excellent with that of hospices' rate of volunteer hours per patient day, controlling for other organizational characteristics. RESULTS: Three hundred five hospice programs (67% freestanding and 20.7% for profit) submitted 57,353 surveys in 2006 (54.2% female decedents and 47.4% with cancer). Hospice programs reported on average 0.71 hours per patient week (25th percentile: 0.245 hours per patient week; 75th percentile: 0.91 volunteer hours per patient week; and 99 th percentile: 3.3 hours per patient week). Those hospice programs in the highest quartile of volunteer usage had higher overall satisfaction compared with those in the lowest-quartile usage of volunteers (75.8% reported excellent overall quality of care compared with 67.8% reporting excellent in the lowest quartile. After adjustment for hospice program characteristics, hospice programs in the highest quartile had highest overall rating of the quality of care (coefficient=0.06, 95% confidence interval=0.04, 0.09). CONCLUSION: In this cross sectional study, hospice programs with higher use of volunteers per patient day were associated with bereaved family member reports that the hospice program quality of care was excellent. PMID- 20303029 TI - The experience of breathlessness: the social course of chronic obstructive pulmonary disease. AB - CONTEXT: There is a trend toward extending palliative care to nonmalignant diseases. There is no evidence that chronic obstructive pulmonary disease (COPD) requires its own model. OBJECTIVES: The aim of this study was to investigate how the experience of breathlessness in COPD influences patients' attitudes toward the end of life and their quality of life. METHODS: Eighteen patients were purposively sampled. Data were collected through in-depth interviews and participant observation during outpatient consultations. Narrative methods were used to analyze the data. RESULTS: Treatment-seeking in COPD deviated from prototypical trajectories. Contact with health care was postponed to crisis point. Treatment did not follow diagnosis because of how the diagnosis was given. Help was sought when the symptom had acquired meaning in a person's life. The future did not feature in the interviews. CONCLUSION: Good communication practices are fundamental in the care for COPD patients. Particularly, diagnosis and prognosis need to be rethought in a model to suit the condition of COPD. PMID- 20303028 TI - A comparison of two spirituality instruments and their relationship with depression and quality of life in chronic heart failure. AB - Spirituality is a multifaceted construct related to health outcomes that remains ill defined and difficult to measure. Spirituality in patients with advanced chronic illnesses, such as chronic heart failure, has received limited attention. We compared two widely used spirituality instruments, the Functional Assessment of Chronic Illness Therapy-Spiritual Well-Being (FACIT-Sp) and the Ironson-Woods Spirituality/Religiousness Index (IW), to better understand what they measure in 60 outpatients with chronic heart failure. We examined how these instruments related to each other and to measures of depression and quality of life using correlations and principal component analyses. The FACIT-Sp measured aspects of spirituality related to feelings of peace and coping, whereas the IW measured beliefs, coping, and relational aspects of spirituality. Only the FACIT-Sp Meaning/Peace subscale consistently correlated with depression (r=-0.50, P<0.0001) and quality of life (r=0.41, P=0.001). Three items from the depression measure loaded onto the same factor as the FACIT-Sp Meaning/Peace subscale (r=0.43, -0.43, and 0.71), whereas the remaining 12 items formed a separate factor (Cronbach's alpha=0.82) when combined with the spirituality instruments in a principal component analysis. The results demonstrate several clinically useful constructs of spirituality in patients with heart failure and suggest that psychological and spiritual well-being, despite some overlap, remain distinct phenomena. PMID- 20303030 TI - Single- vs. multiple-item instruments in the assessment of quality of life in patients with advanced cancer. AB - Although multidimensional instruments are usually used to measure quality of life in advanced cancer patients, recent research suggests that single-item assessments can provide a reliable measure. Using the Functional Assessment of Cancer Therapy-General (FACT-G) instrument as a gold standard, we assessed the performance of the Edmonton Symptom Assessment System "feeling of well-being" (ESAS WB) item. We reviewed the data from 213 patients enrolled in six clinical trials. We determined the association between baseline ESAS WB and FACT-G total and subscale domain scores (Physical Well-being [PWB], Social/Family Well-being [SWB], Emotional Well-being [EWB], and Functional Well-being [FWB]. We also calculated the association between baseline (T1) and second (T2) observations of ESAS WB and of FACT-G total score. In addition, we predicted the change in FACT-G predicted by the ESAS WB score using regression analysis. Mean age was 60 (SD 12) years and 48% were female. The Spearman correlation coefficient of ESAS WB and FACT-G was -0.48 (P<0.0001). Correlations with FACT-G subscale domains were also highly significant, except for the SWB domain (P=0.08). The Pearson correlation coefficient for T1-T2 in ESAS WB and FACT-G for 146 patients was -0.36 (P<0.0001). The change in ESAS WB corresponding to FACT-G published minimally important difference was -0.24 for 3, -1.55 for 5, and -2.87 for 7, respectively. These results suggest that the single-item measure ESAS WB best reflects the total score on the FACT-G and PWB, EWB, and FWB domains but not on the SWB domain. PMID- 20303032 TI - Parent pain responses as predictors of daily activities and mood in children with juvenile idiopathic arthritis: the utility of electronic diaries. AB - The present study used electronic diaries to examine how parent responses to their child's pain predict daily adjustment of children with juvenile idiopathic arthritis (JIA). Nine school-aged children with JIA along with one of their parents completed thrice-daily assessments of pain-related variables, activity participation, and mood using handheld computers (Palm pilots) for 14 days, yielding a potential of 42 child and parent assessments for each dyad. Children provided information on current pain level, mood, and participation in social, physical, and school activities. Parents independently rated their own mood as well as their behavioral responses to their child's pain at the same time points using a separate handheld computer. Results of multilevel modeling analyses demonstrated that use of "protective" pain responses by parents significantly predicted decreases in child activity and positive mood, with an even stronger inverse relationship between protective pain response and positive mood observed in children with higher than average disease severity. Protective pain responses were not found to be significantly predictive of daily negative mood in children. The use of "distracting" responses by parents significantly predicted less child activity restrictions but only in children having higher disease severity. There also was an unexpected trend in which parent use of more distracting pain responses tended to be associated with lower child positive mood. These preliminary findings suggest the importance of the parent in influencing adjustment in children with JIA and lend support to the incorporation of parents into comprehensive pain management approaches. The potential benefits of using electronic daily diaries as a strategy to examine pain and adjustment in children with JIA pain are discussed. PMID- 20303031 TI - Psychometric and clinical assessment of the 10-item reduced version of the Fatigue Scale-Child instrument. AB - Fatigue is one of the most debilitating conditions associated with cancer and anticancer therapy. The lack of reliable and valid self-report instruments has prevented accurate assessment of fatigue in pediatric oncology patients. The purpose of this study was to identify the most sensitive and specific score, that is, the "cut score," on the Fatigue Scale-Child (FS-C) to identify those children with high cancer-related fatigue in need of clinical intervention. We first used Rasch methods to identify the items on the FS-C that distinguished children with high cancer-related fatigue from other children; our findings indicated that the FS-C needed to be reduced from 14 items to 10 items. We then assessed the 10-item FS-C for its psychometric properties and applied the receiver operating characteristics curve analysis to the FS-C responses from 221 children (aged 7-12 years) receiving anticancer treatment. The cut score identified with 75% sensitivity and 73.5% specificity was 12; 73 (33%) patients scored 12 or higher. Findings from this validated instrument provide a needed guide for clinicians to interpret fatigue scores and provide clinical interventions for this debilitating condition to their pediatric patients with cancer. PMID- 20303033 TI - Dying tax free: the modern advance directive and patients' financial values. AB - Advance directives are often used to help patients articulate their end-of-life treatment preferences and guide proxy decision makers in making health care decisions when patients cannot. This case study and commentary puts forth a situation in which a palliative care consultation team encountered a patient with an advance directive that instructed her proxy decision maker to consider estate tax implications when making end-of-life decisions. Following presentation of the case, the authors focus on two ethical issues: 1) the appropriateness of considering patients' financial goals and values in medical decision making and 2) whether certain kinds of patient values should be considered more or less relevant than others as reasons for expressed treatment preferences. Clinicians are encouraged to accept a wide range of patient values as relevant to the clinical decision-making process and to balance the influence of those values with more traditional notions of clinical harm and benefit. PMID- 20303034 TI - Blood still kills: six strategies to further reduce allogeneic blood transfusion related mortality. AB - After reviewing the relative frequency of the causes of allogeneic blood transfusion-related mortality in the United States today, we present 6 possible strategies for further reducing such transfusion-related mortality. These are (1) avoidance of unnecessary transfusions through the use of evidence-based transfusion guidelines, to reduce potentially fatal (infectious as well as noninfectious) transfusion complications; (2) reduction in the risk of transfusion-related acute lung injury in recipients of platelet transfusions through the use of single-donor platelets collected from male donors, or female donors without a history of pregnancy or who have been shown not to have white blood cell (WBC) antibodies; (3) prevention of hemolytic transfusion reactions through the augmentation of patient identification procedures by the addition of information technologies, as well as through the prevention of additional red blood cell alloantibody formation in patients who are likely to need multiple transfusions in the future; (4) avoidance of pooled blood products (such as pooled whole blood-derived platelets) to reduce the risk of transmission of emerging transfusion-transmitted infections (TTIs) and the residual risk from known TTIs (especially transfusion-associated sepsis [TAS]); (5) WBC reduction of cellular blood components administered in cardiac surgery to prevent the poorly understood increased mortality seen in cardiac surgery patients in association with the receipt of non-WBC-reduced (compared with WBC-reduced) transfusion; and (6) pathogen reduction of platelet and plasma components to prevent the transfusion transmission of most emerging, potentially fatal TTIs and the residual risk of known TTIs (especially TAS). PMID- 20303035 TI - Is there a role for autologous/placental red blood cell transfusions in the anemia of prematurity? AB - Because most extremely preterm infants with birth weight less than 1000 g need red blood cell transfusions, many attempts have been made to collect, process, and store placental blood (ie, umbilical cord blood) for autologous transfusions. Although it is feasible to do this, multiple problems in doing so including insufficient volumes collected, clotting, hemolysis, bacterial contamination, failure to significantly supplant need for allogeneic transfusions, and high costs have led many to question whether, on balance, autologous/placental red blood cell transfusion offers clinically significant benefits. PMID- 20303036 TI - Optimization of leukocyte collection and monocyte isolation for dendritic cell culture. AB - Leukapheresis is the method of choice to collect monocytes for dendritic cell (DC) culture. Improvement of cell separators and cell collection software have enabled the collection of 10(9) monocytes for the generation of monocyte-derived DCs, which is sufficient to prepare a DC vaccine series. However, leukapheresis works with the technique of differential centrifugation which is not applicable to selectively collect mononuclear cells of similar density. After leukapheresis, thus, additional preparation steps are required to isolate and enrich the desired monocyte population. The cell isolation and cultivation techniques depend on the quality of the original leukocyte harvest due to the monocyte yield and the content of residual erythrocytes and platelets. Monocyte elutriation from the leukapheresis product shows a high monocyte recovery of 80%. However, only 30% of the isolated monocytes can be developed into mature DCs. The factors responsible for DC maturation and the development of different DC subsets are the subject of current research. PMID- 20303037 TI - A strategic approach to the problems of providing rhesus D-negative blood transfusion in geographic areas with low RhD negativity: a Nigerian perspective. AB - In contrast to the white prevalence, the frequency of rhesus D (RhD) negativity in the Nigerian population ranges from less than 1% to about 6% in the different ethnic population groups across the country. Consequently, there is often a severe scarcity of RhD-negative blood in Nigeria, leading to undue delay in transfusing RhD-negative patients. This situation has led to the prolongation of hospital stays as well as increased morbidity and mortality in affected patients. The problem is compounded by the general unavailability of donor RhD-negative blood, which is partially related to a suboptimal national blood transfusion service. This situation has thus relegated the responsibilities of donor recruitment and blood collection to individual hospital blood banks. This has led to the necessity of finding a variety of ways to mitigate the daunting problem of the provision of RhD-negative donor blood in Nigeria. In this article, we review the roles, advantages, and disadvantages of various methods including the use of autologous donations, D(u) testing, inter-blood bank transfers, voluntary RhD negative donor recall, family donations, and cryopreservation to ameliorate the problem. The real need is nonetheless to optimize the functional capacity of the Nigerian National Blood Transfusion Service. PMID- 20303038 TI - Arnault Tzanck, MD (1886-1954). AB - Arnault Tzanck's name is attached to an apparatus he invented that was widely used for transfusing blood in France between the wars, as well a simple test he devised using the microscopic analysis of scrapings from skin cancer lesions, different ganglia, and some forms of dermatitis especially pemphigus. The Tzanck smear is still widely used as a test for herpes, among other diseases. He also experimented with different methods of preserving blood and blood substitutes. Tzanck's most lasting contribution was in the organization of blood transfusion in France that eventually resulted in the creation of the Centre National de Transfusion Sanguine (National Blood Transfusion Center), which was established in 1949 with Tzanck as its first director. In the process, Tzanck educated a whole generation of serologists and immunologists, including Jean Dausset, Marcel Bessis, and Jean Pierre Soulier. PMID- 20303039 TI - The usefulness of pathogen inactivation during an outbreak of the new strain of influenza (H1N1). PMID- 20303040 TI - Clinical and radiographic outcomes of implants immediately placed in fresh extraction sockets. AB - OBJECTIVE: The objective of this study was to examine the clinical and radiographic results of implants placed in fresh extraction sockets for 2 years of function. STUDY DESIGN: Ten patients were presented a treatment protocol involving the extraction of their remaining mandibular teeth and immediate placement of 4 implants (2 in fresh extraction sockets; test group (TG, n = 20), 2 in mature bone; control group (CG, n = 20). Descriptive statistics for the differences between baseline and follow-up values were assessed by chi-square test. RESULTS: None of the implants lost osseointegration. The MPI Score 0 was 80.3% in SG, 82.7% in CG, and MPI Score 1 was 13.4% in SG and 14.9% in CG at the end of 1 year, and remained stable after 2 years. No significant difference in MPI, MBI, KMW, and PPD were observed between the baseline examination and controls. Chances in MBL in CG were slightly higher in SG. CONCLUSION: Placement of implants in fresh extraction sockets is a reliable treatment alternative. PMID- 20303041 TI - Long-term treatment of Langerhans cell histiocytosis of the mandibular condyle with indomethacin. AB - Langerhans cell histiocytosis (LCH) most commonly occurs as a localized solitary bone lesion and appears predominantly in pediatric patients. LCH is characterized by the proliferation and accumulation of Langerhans cells which may cause pain and adjacent soft-tissue swelling. This disease is of clinical importance to dental professionals because LCH commonly involves the oral and maxillofacial region and early symptoms can be manifested in the jaw and, when overlooked, may result in extensive destruction of the involved structures. Considering the fact that this is a relatively rare entity, close investigation of the cases that are encountered are warranted. Herein we report a case of LCH occurring in the left condyle of an 11-year-old boy that initially showed clinical symptoms mimicking an abscess of the temporomandibular joint. The clinical and radiographic features, differential diagnosis, treatment, and long-term follow-up of this patient with indomethacin are presented. PMID- 20303042 TI - Metastatic renal cell carcinoma to the oral cavity and clear cell mucoepidermoid carcinoma: comparative clinicopathologic and immunohistochemical study. AB - BACKGROUND: Metastatic clear cell renal cell carcinoma (CCRCC) should be considered in differential diagnosis of intraoral clear cell tumors, including mucoepidermoid carcinoma (MEC). OBJECTIVE AND STUDY DESIGN: We compared the clinical, histologic, histochemical, and immunohistochemical characteristics of 9 oral metastatic CCRCCs and 8 intraoral clear cell MECs. RESULTS: Oral metastatic CCRCC affected salivary-gland containing tissues in 7 cases (78%). Microscopically, oral metastasis revealed a proliferation of neoplastic clear cells arranged in an alveolar pattern with central blood vessels, features that were not seen in any intraoral clear cell MEC. Mucicarmine staining was positive only in clear cell MEC. Immunohistochemistry showed similarities in cytokeratin expression; vimentin and CD10 were expressed in all oral metastatic CCRCCs but in only 1 clear cell MEC each. CONCLUSIONS: Besides clinical history, the alveolar pattern, vessel distribution, absence of mucicarmine staining, and vimentin and CD10 immunoexpression are useful in histologic differential diagnosis of CCRCC and clear cell MEC. PMID- 20303043 TI - A salivary gland adenocarcinoma mimicking a microcystic adnexal carcinoma. AB - The microcystic adnexal carcinoma (MAC) is a rare, slow-growing but locally aggressive neoplasm arising in the midface and lips of middle-aged adults. The MAC is histologically characterized by deeply infiltrating nests and islands of basaloid or squamous cells forming cysts and ductal structures, proliferating in a dense sclerotic stroma and occasionally exhibiting perineural invasion. We describe a salivary gland adenocarcinoma arising in the lower lip, characterized by ductal structures and cords, 3-5 cell layers in thickness, set in a dense fibrous stroma and also invading nerves, thus mimicking a MAC in both its clinical and its histopathologic appearance. The diagnostic dilemma presented by this lesion is discussed, along with a differential diagnosis and brief review of the literature. PMID- 20303044 TI - A case of primary combined neuroendocrine carcinoma with squamous cell carcinoma in the upper gingiva. AB - Neuroendocrine carcinoma is a rare neoplasm that occurs widely in various organs and tissues. The biological behavior of this tumor in the oral region remains poorly understood. We encountered an extremely rare case of combined neuroendocrine carcinoma with squamous cell carcinoma, occurring at the buccal gingiva in a 62-year-old woman. Left partial maxillectomy was performed. Histological examinations revealed solid nests with extensive necrosis and nuclear palisading at the periphery. The tumor also showed areas of stratified neoplastic squamous differentiation. Immunohistochemically, tumor nests stained positive for synaptophysin, chromogranin, N-CAM (CD56), and neuron-specific enolase. Strong positivity was seen for K14 and K17 in the squamous component and for K7 in the neuroendocrine component. Both components showed K19 staining. Cells with squamous differentiation and K14 staining occasionally expressed p63. The patient showed no evidence of disease as of 23 months postoperatively. Given the aggressive characteristics of neuroendocrine carcinoma, strict follow-up has been performed. PMID- 20303045 TI - Calcifying odontogenic cyst with odontogenic keratocyst: a case report and review of the literature. AB - The calcifying odontogenic cyst (COC), first identified as a separate and distinct lesion by Gorlin et al. in 1962, is an uncommon benign lesion, consisting of a proliferation of odontogenic epithelium and scattered nests of ghost cells and calcifications that may form the lining of a cyst or present as a solid mass. The COC occurs alone or occasionally with odontomas or other odontogenic tumors, and it is this variable histology and clinical behavior that has raised the question of whether or not it is a cyst or a true neoplasm. The odontogenic keratocyst (OKC) is a locally aggressive odontogenic cyst lined by parakeratinizing epithelium that also exhibits characteristics of a neoplasm, including rapid growth, a high rate of recurrence when treated conservatively, and the presence of a gene mutation. We describe a patient diagnosed with an OKC of the mandible that arose simultaneously with a COC of the anterior maxilla. The occurrence of 2 "cystic neoplasms" in the same patient is an occurrence which to our knowledge has not been previously reported. We discuss the significance of the case and review the current literature regarding these lesions. PMID- 20303046 TI - Canine transmigration: comprehensive literature review and report of 4 new Australian cases. AB - Canine transmigration is a rare dental anomaly unique to the mandibular arch, involving intraosseous migration of the unerupted tooth across the midline. Currently, there is a lack of consensus on the definition of transmigration. This report suggests a unified definition of transmigration, that being when a canine has crossed the midline by more than half its length. Numerous publications reporting mandibular canine transmigration therefore cannot be considered as being truly transmigrated. Here we undertake a comprehensive review of the literature, and report 4 new cases of transmigrated mandibular canines, 2 of which present with unique features. One case shows a vertically positioned transmigrated canine, whereas the other shows a horizontally transmigrated canine underlying an impacted canine. Furthermore, this cohort is the first to be reported in an Australian population. PMID- 20303047 TI - Carotid body paraganglioma manifesting as a malignant solitary mass on imaging: a case report. AB - A 58-year-old woman presented with a lump on the left side of the neck. Investigations by ultrasound-guided fine needle aspiration, magnetic resonance imaging, and positron emission tomography were all indicative of a diagnosis of a solitary malignant mass with no primary lesion identified. The patient underwent a level I-V leftside selective neck dissection. The histology results reported the mass as a carotid body paraganglioma. These are highly vascular lesions. Paragangliomas have characteristic features on the different imaging modalities; in this case they were atypical. This article reviews the main imaging modalities of paragangliomas and cytologic findings of the fine needle aspiration, which is not often performed for these cases owing to their high vascularity. PMID- 20303049 TI - Barodontalgia: what have we learned in the past decade? AB - This article reviews the current knowledge regarding barodontalgia, a barometric pressure-related oral (dental and other) pain. Contemporary classification, prevalence, and incidence, features, etiology, and diagnosis of this entity are presented regarding flight and diving conditions. Summarizing the past decade data, three-fourths of episodes were described as severe, sharp, and localized pain. Barodontalgia affects 11.9% of divers and 11.0% of military aircrews with a rate of 5 episodes/1,000 flight-years. Upper and lower dentitions were affected equally in flight, but more upper than lower dentition were affected in diving. The most prevalent etiologic pathologies for in-flight dental pain were faulty dental restorations (including dental barotrauma) and dental caries without pulp involvement (29.2%), necrotic pulp/periapical inflammation (27.8%), vital pulp pathology (13.9%), recent dental treatment (11.1%), and barosinusitis (9.7%). This review refutes 3 generally accepted conventions: According to the results, the current in-flight barodontalgia incidence is similar to the incidence in the first half of the 20th century, the weighted incidence of barodontalgia among aircrews are similar to the weighted incidence among divers, and the role of facial barotrauma in the etiology of in-flight barodontalgia is minor. PMID- 20303048 TI - Human pulp responses to in-office tooth bleaching. AB - OBJECTIVE: To evaluate and compare the responses of human incisor and premolar pulps after bleaching. STUDY DESIGN: A bleaching agent with 38% hydrogen peroxide (H(2)O(2)) was applied on the buccal surface of 10 sound lower teeth (G1: 6 premolars; G2: 4 incisors) for 45 minutes. Three premolars and 3 incisors that received only rubber/pumice prophylaxis were used as control groups G3 and G4, respectively. Two days after the bleaching procedure, the teeth were extracted and processed for histologic evaluation. RESULTS: Only in G2 (4 incisors) were any changes in the pulp detected. In the coronal pulp there was a large zone of coagulation necrosis. The radicular pulp showed mild inflammatory changes manifested as an accumulation of mononuclear cells around congested and dilated blood vessels. No pulpal damage was seen in either of the control groups (G3 and G4) or in group G1. CONCLUSION: Bleaching with 38% H(2)O(2) for 45 minutes causes irreversible pulp damage in lower incisors but not in premolars. PMID- 20303050 TI - Transdentinal protective role of sodium ascorbate against the cytopathic effects of H2O2 released from bleaching agents. AB - OBJECTIVES: The objectives of this study were to evaluate the transdentinal cytotoxicity of 10% and 16% carbamide peroxide gel (CP), as well as the ability of the antioxidant, 10% sodium ascorbate (SA), to protect the odontoblasts in culture. STUDY DESIGN: Human dentin discs of 0.5-mm thickness were obtained and were placed into artificial pulp chambers. MDPC-23 odontoblastlike cells were seeded on pulp surface of the discs and the following groups were established: G1 No Treatment (control), G2-10% SA/6hs, G3-10%/CP6hs, G4-10%SA/6hs+10%CP/6hs, G5 16%CP/6hs, and G6-10%SA/6hs+16%CP/6hs. The cell viability was measured by the MTT assay. RESULTS: In groups where 16% CP was used, decreased cell viability was observed. Conversely, the application of 10% SA on the dentin discs, before the use of the CP, reduced the cytotoxic effects of these products on cells. CONCLUSIONS: The 16% CP cause a significant decrease in MDPC-23 cell viability and 10% SA was able to partially prevent the toxic effects of CP. PMID- 20303051 TI - Morphological assessment of dentine and cementum following apicectomy with Zekrya burs and Er:YAG laser associated with direct and indirect Nd:YAG laser irradiation. AB - OBJECTIVES: This study aimed to assess the apical surface morphology of maxillary central incisors resected 3.0 mm from the tooth apex using Zekrya burs or Er:YAG laser, with or without subsequent direct Nd:YAG laser irradiation (apical and buccal surfaces) and indirect irradiation (palatal surface). STUDY DESIGN: Forty maxillary central incisors were instrumented and obturated. The roots were divided into 4 groups according to the root resection method (Zekrya bur or Er:YAG laser - 1.8 W, 450 mJ, 4 Hz, 113 J/cm(2)) and further surface treatment (none or Nd:YAG laser - 2.0 W, 100 mJ, 20 Hz, 124 J/cm(2)). The teeth were prepared for SEM analysis. Scores ranging from 1 to 4 were attributed to cut quality and morphological changes. The data were analyzed by the Kruskal-Wallis test and by Dunn's test. RESULTS: SEM images showed irregular surfaces on the apical portions resected with Zekrya burs, with smear layer and grooves in the resected dentine and slight gutta-percha displacement and plasticization. On the other hand, apicectomies carried out with Er:YAG laser showed morphological changes compatible with ablated dentine, with rough surfaces and craters. In spite of the presence of plasticized gutta-percha, with the presence of bubbles, an irregular adaptation of the filling material to the root walls was also observed. Direct Nd:YAG laser irradiation of the apical and buccal surfaces of the resected roots resulted in areas of resolidification and fusion in the dentine and cementum, with a vitrified aspect; indirect Nd:YAG laser irradiation of the palatal surfaces yielded a lower number of changes in the cementum, with irregular resolidification areas. CONCLUSIONS: There were no differences in terms of cut quality between the use of burs and Er:YAG laser or between the 2 surfaces (apical and buccal) treated with Nd:YAG laser with direct irradiation. However, morphological changes were significantly less frequent on surfaces submitted to indirect irradiation (palatal) when compared with those directly irradiated. PMID- 20303052 TI - Neuropathic orofacial pain after dental implant placement: review of the literature and case report. AB - Persistent and chronic pain is more common in the head and neck region than in any other part of the body; therefore, dentists are more likely to encounter these rather complex cases in their practices. In this report, we present a brief review of neuropathic orofacial pain (NOP) that can begin after deafferentation of trigeminal nerve fibers after root canal treatment, apicoectomy, tooth extraction, or implant placement or idiopathically. A case of NOP occurring after a surgical implant procedure in a 62-year-old woman is presented. Continuous pain started 6 months after the placement of 8 dental implants in the maxilla, at the time of positioning the prosthesis on her implants. After being subjected to a physical examination and relevant complementary radiologic imaging, the patient was diagnosed with an NOP secondary to nerve impingement due to dental implant placement as well as myofascial head and neck pain. PMID- 20303054 TI - Cystic lymphoid hyperplasia of the parotid gland in HIV-positive and HIV-negative patients: quantitative immunopathology. AB - BACKGROUND: Benign lymphoepithelial lesions of the parotid include a spectrum of disorders ranging from lymphoepithelial sialadenitis (LESA) of Sjogren syndrome to lymphoepithelial cysts (LEC) and both human immunodeficiency virus (HIV) related and -unrelated cystic lymphoid hyperplasia (CLH). They share a common microscopic appearance characterized by epimyoepithelial islands and/or epithelial lined cysts in a lymphoid stroma. However, they differ greatly regarding their etiology, clinical presentation, and management. OBJECTIVE: The purpose of this study was to establish specific immunophenotypic profiles for these diverse disease entities. STUDY DESIGN: Four cases of HIV+ CLH, 5 cases of HIV- CLH, 3 cases of LESA of Sjogren syndrome, and 3 cases of sporadic LEC were quantitatively analyzed for distribution of lymphoreticular cell subpopulations, using antibodies against CD20, CD45RO, CD4, CD8, CD57, and CD68. RESULTS: The cystic lesions in both the HIV+ and HIV- cases were microscopically analogous. However, a marked decrease in the interfollicular CD4:CD8 ratio was observed in all HIV+ CLH cases, which was statistically significant when compared with the HIV- cases (P = .02) and cases of LESA of Sjogren syndrome (P = .03). No significant differences regarding the distribution of CD20+ B lymphocytes in epithelial cyst lining or the interfollicular or follicular distribution of CD20+, CD45RO+, CD57+, and CD68+ cells were present among the different groups. CONCLUSION: Analysis of the interfollicular CD4:CD8 ratio may offer a simple immunophenotypic approach in the distinction of HIV+ from other lymphoepithelial lesions of the parotid gland, when HIV status is unknown and p24 immunohistochemistry is not readily available. PMID- 20303053 TI - Molecular methodology to assess the impact of cancer chemotherapy on the oral bacterial flora: a pilot study. AB - OBJECTIVE: This pilot study determined the profile of the oral bacterial flora in an outpatient cancer population before and after chemotherapy using molecular techniques. STUDY DESIGN: We recruited 9 newly diagnosed breast cancer patients scheduled for induction chemotherapy. All were seen immediately before chemotherapy, and 7 to 14 days later. At both visits, we performed oral evaluations and obtained mucositis grading (with the World Health Organization [WHO] scale), absolute neutrophil counts (ANC), and bacterial samples from the buccal mucosa. Bacterial DNA was isolated, and 16S ribosomal RNA gene clonal libraries were constructed. Sequences of genes in the library were used to determine species identity by comparison to known sequences. RESULTS: After chemotherapy, WHO scores of 0 and 1 were in 3 and 6 patients, respectively, and mean ANC (+/-SD) dropped from 3326 +/- 463 to 1091 +/- 1082 cells/mm(3). From pre and post-chemotherapy samples, 41 species were detected, with a predominance of Gemella haemolysans and Streptococcus mitis. More than 85% of species have not been previously identified in chemotherapy patients. Seven species appeared exclusively before chemotherapy and 25 after chemotherapy. After chemotherapy, the number of species per patient increased by a mean of 2.6 (SD = 4.7, P = .052). CONCLUSION: We identified species not previously identified in chemotherapy patients. Our results suggest a shift to a more complex oral bacterial profile in patients undergoing cancer chemotherapy. PMID- 20303055 TI - Survivin as a potential early marker in the carcinogenesis of oral submucous fibrosis. AB - OBJECTIVE: Oral submucous fibrosis (OSF) is a chronic precancerous condition. Survivin is one of the inhibitors of apoptosis protein, and is focused on owing to its unique therapeutic and prognostic potential. STUDY DESIGN: To determine the potential involvement of survivin in the carcinogenesis of OSF, we analyzed the relationship between the survivin and clinical characteristic. RESULTS: Immunohistochemistry was used to show that survivin expression levels were significantly higher in the oral squamous cell carcinoma transformed from OSF group compared with normal group (P < .01) and OSF group (P < .01). In the different stages of OSF, survivin expression exhibited difference as well. Furthermore, Western blotting and reverse-transcription polymerase chain reaction analysis confirmed the increased expression of survivin in the carcinogenesis of OSF. CONCLUSION: These results suggest that survivin plays an important role during the malignant transformation of OSF and may provide an indication to early prevention and diagnosis in the progression of OSF. PMID- 20303056 TI - Metastases in odontogenic cysts: literature review and case presentation. AB - Malignant tumors in the oral cavity are relatively rare. About 5% of all malignant growths in the body are localized in the oral cavity. The vast majority of oral malignancies are primary tumors with squamous cell carcinoma being the most frequent and sarcomas occurring very seldom. Secondary tumors caused by hematogenous spread arising from a tumor localized elsewhere in the body are extremely rare. About 1% of all oral cancers are metastases to the jawbones and the surrounding soft tissues. Metastases to the jaws are mainly caused by malignant tumors of the breast, lung, kidney, bone, and colon. They occur in the late state of the disease and are regularly detected by staging examinations including scintigraphy. Even more rare are metastases into odontogenic cysts. Odontogenic cysts include dentigerous cysts, periapical or radicular cysts, and the keratocysts-nowadays declared as keratocystic odontogenic tumor. The incidence of odontogenic cysts is about 10% to 15% of all oral biopsies and therefore general dentists are frequently faced with these types of lesions. The aim of this study was to review the literature regarding metastasis into odontogenic cysts and to further highlight this rare entity with the help of a clinical case. PMID- 20303057 TI - Oral metastasis of alveolar soft-part sarcoma: a case report and review of literature. AB - Alveolar soft-part sarcoma (ASPS) is a rare malignant neoplasm with uncertain histogenesis and with a distinctive morphology. It has been described in the oral cavity, but this is the first report of ASPS metastasizing to the maxillary tuber region. A 27-year-old male patient, who was under chemotherapy treatment for ASPS of the thigh, presented in our dental clinic with a painless and pedunculated nodule on the right tuber maxillae. The nodule was erythematous with smooth and lobular surface, measuring 3 cm in maximum diameter. An incisional biopsy was performed and the diagnosis of metastatic ASPS was made. Histologically, the tumor was characterized by a proliferation of polyhedral cells in pseudoalveolar pattern. Tumor cells were large, showing granular cytoplasm, periodic acid-Schiff positive diastase-resistant intracytoplasmic material, and vesicular nuclei with prominent nucleoli. Unfortunately, the patient died 2 months after the diagnosis of the oral metastasis. Metastases of ASPS to the mouth are very rare and indicate a poor prognosis. PMID- 20303058 TI - A comparison of nickel-titanium rotary instruments manufactured using different methods and cross-sectional areas: ability to resist cyclic fatigue. AB - OBJECTIVE: This study examined the effect of the manufacturing methods (ground, electropolished, and twisted) and the cross-sectional area (CSA) of nickel titanium (NiTi) rotary instruments on their cyclic fatigue resistance. STUDY DESIGN: A total of 80 NiTi rotary instruments (ISO 25/.06 taper) from 4 brands (K3, ProFile, RaCe, and TF) were rotated in a simulated root canal with pecking motion until fracture. The number of cycles to failure (NCF) was calculated. The CSA at 3 mm from the tip of new instruments of each brand was calculated. The correlation between the CSA and NCF was evaluated. All fractured surfaces were analyzed using a scanning electron microscope to determine the fracture mode. RESULTS: The TF instruments were the most resistant to fatigue failure. The resistance to cyclic failure increased with decreasing CSA. All fractured surfaces showed the coexistence of ductile and brittle properties. CONCLUSION: The CSA had a significant effect on the fatigue resistance of NiTi rotary instruments. PMID- 20303059 TI - Use of computerized tomography for diagnosis and follow-up after endodontic surgery: clinical case report with 8 years of follow-up. AB - Computerized tomography (CT) is a valuable tool for diagnosis and planning in conventional and surgical endodontic therapy. This case report describes the use of CT in the diagnosis of a periapical lesion undetected by periapical radiography in the mandibular molar area. The CT also showed a possible mesial root perforation associated with the lesion. Following CT, surgical planning, periradicular curettage, and sealing of the root perforation were performed. Eight years after surgery, cone beam CT revealed periapical bone repair. Computerized tomography can be an important resource for diagnosis and planning in conventional and surgical endodontic therapy, as well as for evaluation of post-treatment bone repair. PMID- 20303060 TI - Endodontic photoactivated disinfection using a conventional light source: an in vitro and ex vivo study. AB - OBJECTIVE: The antimicrobial effect of photoactivated disinfection (PAD) using toluidine blue and an LED lamp was tested on endodontic pathogens in planktonic suspension and after inoculation into extracted teeth. Irradiation time was limited to 30 seconds. STUDY DESIGN: The effect of PAD on planktonic suspensions of Escherichia coli, Candida albicans, Enterococcus faecalis, Fusobacterium nucleatum, and Streptococcus intermedius was analyzed using Poisson regression. Moreover, cultures of S. intermedius were inoculated into prepared root canals of extracted molars. The effect of PAD performed immediately after inoculation or after overnight bacterial incubation was determined by a 2-sample t test. RESULTS: Photoactivated disinfection yielded significant reductions (P < .001) in the viable counts of all organisms in planktonic suspension. The PAD treatment of S. intermedius in root canals yielded a mean log10 reduction of 2.60 (P < .001) immediately after inoculation and of 1.38 (P < .001) after overnight incubation. CONCLUSION: Photoactivated disinfection using a conventional light source strongly reduces the number of viable endodontic pathogens in planktonic suspension and in root canals. PMID- 20303061 TI - Analysis of heavy metal contents in gray and white MTA and 2 kinds of Portland cement: a preliminary study. AB - OBJECTIVE: The levels of 10 heavy metals (arsenic, bismuth, cadmium, chromium, copper, iron, lead, manganese, nickel, and zinc) in gray Portland cement (GPC), white Portland cement (WPC), gray MTA (GMTA), and white MTA (WMTA) were analyzed by inductively coupled plasma-atomic emission spectrometry (ICP-AES). STUDY DESIGN: One gram of each material was digested with 80 degrees C "aqua-regia" (7 mL of 60% HNO3 and 21 mL of 35% HCl), filtered, and analyzed by ICP-AES. The analysis was performed 6 times and the data were analyzed statistically. RESULTS: Arsenic and lead concentrations were the highest in GPC (P < .05). GPC had much more of 7 heavy metals than the other 3 cements (P < .05). GMTA and WMTA had higher purity than GPC and WPC (P < .05), particularly when arsenic content was considered. CONCLUSION: If a clinician is considering using Portland cement versus MTA, the differences in purity may be considered. PMID- 20303062 TI - A variant in LIN28B is associated with 2D:4D finger-length ratio, a putative retrospective biomarker of prenatal testosterone exposure. AB - The ratio of the lengths of an individual's second to fourth digit (2D:4D) is commonly used as a noninvasive retrospective biomarker for prenatal androgen exposure. In order to identify the genetic determinants of 2D:4D, we applied a genome-wide association approach to 1507 11-year-old children from the Avon Longitudinal Study of Parents and Children (ALSPAC) in whom 2D:4D ratio had been measured, as well as a sample of 1382 12- to 16-year-olds from the Brisbane Adolescent Twin Study. A meta-analysis of the two scans identified a single variant in the LIN28B gene that was strongly associated with 2D:4D (rs314277: p = 4.1 x 10(-8)) and was subsequently independently replicated in an additional 3659 children from the ALSPAC cohort (p = 1.53 x 10(-6)). The minor allele of the rs314277 variant has previously been linked to increased height and delayed age at menarche, but in our study it was associated with increased 2D:4D in the direction opposite to that of previous reports on the correlation between 2D:4D and age at menarche. Our findings call into question the validity of 2D:4D as a simplistic retrospective biomarker for prenatal testosterone exposure. PMID- 20303063 TI - High-resolution detection of identity by descent in unrelated individuals. AB - Detection of recent identity by descent (IBD) in population samples is important for population-based linkage mapping and for highly accurate genotype imputation and haplotype-phase inference. We present a method for detection of recent IBD in population samples. Our method accounts for linkage disequilibrium between SNPs to enable full use of high-density SNP data. We find that our method can detect segments of a length of 2 cM with moderate power and negligible false discovery rate in Illumina 550K data in Northwestern Europeans. We compare our method with GERMLINE and PLINK, and we show that our method has a level of resolution that is significantly better than these existing methods, thus extending the usefulness of recent IBD in analysis of high-density SNP data. We survey four genomic regions in a sample of UK individuals of European descent and find that on average, at a given location, our method detects IBD in 2.7 per 10,000 pairs of individuals in Illumina 550K data. We also present methodology and results for detection of homozygosity by descent (HBD) and survey the whole genome in a sample of 1373 UK individuals of European descent. We detect HBD in 4.7 individuals per 10,000 on average at a given location. Our methodology is implemented in the freely available BEAGLE software package. PMID- 20303064 TI - Common variants of large effect in F12, KNG1, and HRG are associated with activated partial thromboplastin time. AB - Activated partial thromboplastin time (aPTT) is associated with risk of thrombosis and coagulation disorders. We conducted a genome-wide association study for aPTT and identified significant associations with SNPs in three coagulation cascade genes, F12 (rs2731672, combined p = 2.16 x 10(-30)), KNG1 (rs710446, combined p = 9.52 x 10(-22)), and HRG (rs9898, combined p = 1.34 x 10( 11)). These three SNPs explain approximately 18% of phenotypic variance in aPTT in the Lothian Birth Cohorts. PMID- 20303065 TI - Development of deciduous and permanent dentitions in the upper jaw of the house shrew (Suncus murinus). AB - The diphyodont tooth replacement in mammals is characterized by a single replacement of a deciduous dentition by a permanent dentition. Despite its significance in mammalian biology and paleontology, little is known about the developmental mechanisms regulating the diphyodont replacement. Because the mouse never replaces its teeth, this study used the house shrew, Suncus murinus, as a model to investigate the control of the diphyodont replacement of a deciduous dentition by successions and additions of permanent teeth. Using morphological and gene expression analyses of serial sections, we have demonstrated the development of the upper dentition of the house shrew. In this species, the deciduous tooth germs are formed but soon become vestigial, whereas the successional and accessional (molar) germs are subsequently formed and developed. There are distinct Shh expression domains in the deciduous, successional, and accessional tooth germs, and those of the latter two germs are identified from the appearance of their primary enamel knots. The developmental sequence of tooth germs in the house shrew indicates that two adjacent primary enamel knots of the successional and accessional germs do not develop simultaneously, but with a constant time lag. We suggest that this mode of tooth succession and accession can be explained by a sequential inhibitory cascade model in which the timing of initiation and the spacing of tooth development are determined by the inhibition from the primary enamel knots of developmentally preceding adjacent tooth germs. PMID- 20303066 TI - Voxelwise meta-analysis of gray matter abnormalities in bipolar disorder. AB - BACKGROUND: We conducted a meta-analysis of gray matter abnormalities in bipolar disorder (BD) using voxel-based morphometry studies to help clarify the structural abnormalities underpinning this condition. METHODS: A systematic review was conducted for voxel-based morphometry studies of patients with BD. Meta-analyses of gray matter differences between BD and control subjects were undertaken using "signed differential mapping," a novel method that, in contrast to previously used techniques, allows inclusion of negative findings and ensures that single studies do not exert undue influence on the results. Meta-regression and subgroup analyses were used to examine the effect of moderator variables on gray matter abnormalities. RESULTS: A total of 21 studies comparing gray matter volumes of 660 BD patients and 770 healthy control subjects were included. Gray matter reduction in left rostral anterior cingulate cortex (ACC) and right fronto insular cortex was associated with BD. Fronto-insular cortex abnormality was not evident in early phases of the illness. In chronic patients, longer duration of illness was associated with increased gray matter in a cluster that included basal ganglia, subgenual ACC, and amygdala. Lithium treatment was associated with enlargement of ACC gray matter volumes, which overlapped with the region where gray matter was reduced in BD. CONCLUSIONS: The most robust gray matter reductions in BD occur in anterior limbic regions, which may be related to the executive control and emotional processing abnormalities seen in this patient population. Clinical factors such as illness duration and lithium treatment also impact on case-control comparisons of gray matter volume. PMID- 20303067 TI - Reward and punishment processing in depression. AB - Depression is a complex and heterogeneous disorder whose cause is poorly understood. Theories on the mechanisms of the disease have often focused on either its neurobiology or its cognitive and behavioral manifestations. Recently, studies exploring how depressed patients process reward and punishment have linked these two facets together. It has been suggested that individuals with a dysfunction in a specialized network of brain regions are unable to exploit affective information to guide behavior. Deficits in this ability might predispose such individuals to develop depression, whereas subsequent restoration of this ability--whether through pharmacological or behavioral treatments--might enable recovery from the disorder. Here we review behavioral, neuroimaging, and computational findings relevant to this hypothesis. There is good evidence that depressed patients exhibit abnormal behavioral responses to rewards and punishments and that these tendencies correspond to aberrant function in frontostriatal systems modulated by the monoamine systems. Furthermore, computational studies have generated testable predictions for how these neural signaling and neurochemical abnormalities might contribute to the symptoms of depression. Combining these approaches--as well as molecular and behavioral work in animals--provides great promise for furthering our understanding of this common and debilitating disease. PMID- 20303068 TI - A novel transgenic mouse for gene-targeting within cells that express corticotropin-releasing factor. AB - Corticotropin-releasing factor (CRF) orchestrates the mammalian endocrine, autonomic, and behavioral stress response and has been implicated in the pathophysiology of illnesses ranging from irritable bowel syndrome to mood and anxiety disorders. CRF is produced and released from a variety of cell types, making it difficult to distinguish the specific role of CRF from other neurotransmitters with which it colocalizes. To clarify the basic biology of the CRF neuron, we must be able to manipulate selectively CRFergic cells. Here we describe a novel transgenic mouse using 3.0 kb of the CRF promoter to drive expression of Cre-recombinase (CRFp3.0Cre). Crossing CRFp3.0Cre with a fluorescent reporter strain results in Cre-dependent green fluorescent protein expression within CRF-producing cells. Thus, CRF cells can be identified for single-cell polymerase chain reaction and electrophysiological procedures. Furthermore, the CRFp3.0Cre transgenic can be combined with other available mouse strains containing a "floxed" gene of interest to allow unparalleled detailed analysis of the CRF system. PMID- 20303069 TI - Induction of depressed mood disrupts emotion regulation neurocircuitry and enhances pain unpleasantness. AB - BACKGROUND: Depressed mood alters the pain experience. Yet, despite its clear clinical relevance, little is known about the cognitive and neural mechanisms underlying this phenomenon. We tested an experimental manipulation to unravel the interaction between depressed mood and pain. We hypothesized that dysregulation of the neural circuitry underlying emotion regulation is the mechanism whereby pain processing is affected during depressed mood. METHODS: Using functional magnetic resonance imaging, we compared the effects of sad and neutral cognitive mood inductions on affective pain ratings, pain-specific cognitions, and central pain processing of a tonic noxious heat stimulus in 20 healthy volunteers. RESULTS: The increase in negative pain-specific cognitions during depressed mood predicted the perceived increase in pain unpleasantness. Following depressed mood induction, brain responses to noxious thermal stimuli were characterized by increased activity in a broad network including prefrontal areas, subgenual anterior cingulate cortex, and hippocampus, as well as significantly less deactivation when compared with pain responses in a neutral mood. The participants who reported the largest increase in pain unpleasantness after the sad mood induction showed greater inferior frontal gyrus and amygdala activation, linking changes in emotion regulation mechanisms with enhancement of pain affect. CONCLUSIONS: Our results inform how depressed mood and chronic pain co-occur clinically and may serve to develop and translate effective interventions using pharmacological or psychological treatment. PMID- 20303070 TI - No neural evidence of statistical learning during exposure to artificial languages in children with autism spectrum disorders. AB - BACKGROUND: Language delay is a hallmark feature of autism spectrum disorders (ASD). The identification of word boundaries in continuous speech is a critical first step in language acquisition that can be accomplished via statistical learning and reliance on speech cues. Importantly, early word segmentation skills have been shown to predict later language development in typically developing (TD) children. METHODS: Here we investigated the neural correlates of online word segmentation in children with and without ASD with a well-established behavioral paradigm previously validated for functional magnetic resonance imaging. Eighteen high-functioning boys with ASD and 18 age- and IQ-matched TD boys underwent functional magnetic resonance imaging while listening to two artificial languages (containing statistical or statistical + prosodic cues to word boundaries) and a random speech stream. RESULTS: Consistent with prior findings, in TD control subjects, activity in fronto-temporal-parietal networks decreased as the number of cues to word boundaries increased. The ASD children, however, did not show this facilitatory effect. Furthermore, statistical contrasts modeling changes in activity over time identified significant learning-related signal increases for both artificial languages in basal ganglia and left temporo-parietal cortex only in TD children. Finally, the level of communicative impairment in ASD children was inversely correlated with signal increases in these same regions during exposure to the artificial languages. CONCLUSIONS: This is the first study to demonstrate significant abnormalities in the neural architecture subserving language-related learning in ASD children and to link the communicative impairments observed in this population to decreased sensitivity to the statistical and speech cues available in the language input. PMID- 20303071 TI - Structure of calcium and zinc pectinate films investigated by FTIR spectroscopy. AB - Calcium and zinc pectinate gels were prepared using a method which allowed calcium or zinc to diffuse from the cross-linking solution through a dialysis membrane to form a gel with amidated low-methoxyl pectin. The gel thus obtained was then dried, and the film structure was studied using FTIR spectroscopy as a function of the cation content (0%, 5%, 10%, and 15% w/v). Important consideration was given to the three functional groups (amide, carboxyl ester, and carboxylate groups) present in the pectin. When the zinc content was increased, the three wavenumber values corresponding to these three functional groups did not change significantly, while for calcium pectinate, the three wavenumber values were shifted profoundly when the amount of calcium ions changed. These results confirm that calcium ions could form stable interactions with carboxylate groups as described by the eggbox model [Grant, G.T.; Morris, E.R.; Rees, D.A.; Smith, P.J.C.; Tho, D. FEBS Lett.1973, 32, 195-198] while the lower coordination number of zinc does not permit a structured gel to develop. PMID- 20303072 TI - Synthetic UDP-furanoses inhibit the growth of the parasite Leishmania. AB - The chemical synthesis of UDP-6-NHAc-6-deoxy-Galf was performed and it led to the isolation of both pure anomers. They were then evaluated together with the previously prepared UDP-furanoses for their anti-parasitic properties against Leishmania donovani promastigotes, one of the agents responsible for visceral leishmaniasis. Amongst them, the unnatural 1,2-trans UDP-6-NHAc-Galf demonstrated a high potency in inhibiting the growth of the parasite. PMID- 20303073 TI - Effect of a serine-to-aspartate replacement on the recognition of chitin oligosaccharides by truncated hevein. A 3D view by using NMR. AB - The interaction of a synthetically prepared mutant peptide of hevein (a well known chitin-binding lectin) Hev32S19D with chitin oligosaccharides (and chitosan analogues) has allowed us to estimate their affinity constants and associated thermodynamic data. The mutant peptide is able to bind chitin oligomers, but with significant decreases in the association constants with chito-oligosaccharides. The determination of the three-dimensional structure of the peptide mutant, by using NMR, has permitted us to deduce that the topology of the backbone is very similar to that of the parent Hev32 peptide. The same is true regarding the orientations of the key aromatic residues Trp21, Trp23, and Tyr30. The decrease in the association constants can be attributed to the different topological orientation of key side chains and to the importance of protein-sugar intermolecular essential hydrogen bonds and CH-pi stacking interactions. The analysis has permitted us to infer the free energy of binding associated with these interactions as well as to estimate the corresponding binding enthalpy. PMID- 20303074 TI - IL-1beta and TNF-alpha alter the glycophenotype of primary human chondrocytes in vitro. AB - Despite the significance of glycoproteins for extracellular matrix assembly in cartilage tissue, little is known about the regulation of the chondrocyte glycophenotype under inflammatory conditions. The present study aimed to assess the effect of IL-1beta and TNF-alpha on specific features of the glycophenotype of primary human chondrocytes in vitro. Using LC-MS, we found that both cytokines increased overall sialylation of N- and O-glycans and induced a shift towards alpha-(2-->3)-linked sialic acid residues in chondrocyte glycoproteins. These results were supported by quantitative PCR showing increased expression of alpha (2-->3) sialyltransferases in treated cells. Moreover, we found that both IL 1beta and TNF-alpha induced a considerable shift from oligomannosidic glycans towards complex-type N-glycans. In contrast, core alpha-(1-->6)-fucosylation of chondrocyte N-glycans was found to be reduced particularly by TNF-alpha. In summary, inflammatory conditions induce specific alterations of the chondrocyte glycophenotype which might affect cell-matrix interactions or the function of endogenous lectins. PMID- 20303075 TI - Concentration-dependent effect of fibrinogen on IgG-specific antigen binding and phagocytosis. AB - In this paper, we aim to characterize fibrinogen-IgG interactions, and explore how fibrinogen alters IgG-mediated phagocytosis. Using enzyme-linked binding assays, we found that fibrinogen binding to IgG is optimized for surfaces coated with high levels of IgG. Using a similar method, we have shown that for an antigen unable to specifically bind fibrinogen, fibrinogen enhances binding of antibodies towards that antigen. For binding of IgG antibodies to cells expressing Fc receptors, we found a bimodal binding response, where low levels of fibrinogen enhance binding of antibody to Fc receptors and high levels reduce it. This corresponds to a bimodal effect on phagocytosis of IgG-coated particles, which is inhibited in the presence of excess IgG during coating of the particles with antibodies and fibrinogen. We conclude that fibrinogen can modulate phagocytosis of IgG-coated particles in vitro by changing IgG binding behavior, and that high fibrinogen levels could negatively affect phagocytosis. PMID- 20303076 TI - Implementation of a novel interpolating method to epicardial potential mapping for atrial fibrillation study. AB - Epicardial potential mapping is an efficient way to visualize the potential distribution on the epicardial surface. We found in our previous study, that the traditional linear interpolation used for the epicardial mapping may cause errors and distortions in reconstruction of the electric activities on the epicardial surface especially during the atrial fibrillation. In this study, we devoted on the implementation of a 3D interpolating method, and verified it in comparison with another interpolating method as well as studying of the mechanism of vagal atrial fibrillation (AF). In case studying, we analyzed the epicardial data from seven canine cardiac models using this method and found the macro-re-entry during the sustainable AF is more likely due to the dispersion of refractoriness in the myocardium and does not demonstrated the focal patterns at the beginning of AF. This indicated that the electrophysiological characteristics of myocardium might have been changed during the paroxysmal atrial fibrillation (PAF). PMID- 20303077 TI - Sewage sludge and liquid pig manure as possible sources of antibiotic resistant bacteria. AB - Within the last decades, the environmental spread of antibiotic resistant bacteria has become a topic of concern. In this study, liquid pig manure (n=305) and sewage sludge (n=111) - used as agricultural fertilizers between 2002 and 2005 - were investigated for the presence of Escherichia coli, Enterococcus faecalis and Enterococcus faecium. Bacteria were tested for their resistance against 40 chemotherapeutics including several "reserve drugs". E. coli (n=613) from pig manure were at a significantly higher degree resistant to streptomycin, doxycycline, spectinomycin, cotrimoxazole, and chloramphenicol than E. coli (n=116) from sewage sludge. Enterococci (Ent. faecalis, n=387, and Ent. faecium, n=183) from pig manure were significantly more often resistant to high levels of doxycycline, rifampicin, erythromycin, and streptomycin than Ent. faecalis (n=44) and Ent. faecium (n=125) from sewage sludge. Significant differences in enterococcal resistance were also seen for tylosin, chloramphenicol, gentamicin high level, fosfomycin, clindamicin, enrofloxacin, moxifloxacin, nitrofurantoin, and quinupristin/dalfopristin. By contrast, aminopenicillins were more effective in enterococci from pig manure, and mean MIC-values of piperacillin+tazobactam and third generation cefalosporines were significantly lower in E. coli from pig manure than in E. coli from sewage sludge. 13.4% (E. coli) to 25.3% (Ent. faecium) of pig manure isolates were high-level multiresistant to substances from more than three different classes of antimicrobial agents. In sewage sludge, high level-multiresistance reached from 0% (Ent. faecalis) to 16% (Ent. faecium). High rates of (multi-) resistant bacteria in pig manure emphasize the need for a prudent - cautious - use of antibiotics in farm animals. PMID- 20303078 TI - Robust stabilizing first-order controllers for a class of time delay systems. AB - In this paper, stabilizing regions of a first-order controller for an all poles system with time delay are computed via parametric methods. First, the admissible ranges of one of the controller's parameters are obtained. Then, for a fixed value of this parameter, stabilizing regions in the remaining two parameters are determined using the D-decomposition method. Phase and gain margin specifications are then included in the design. Finally, robust stabilizing first-order controllers are determined for uncertain plants with an interval type uncertainty in the coefficients. Examples are given to illustrate the effectiveness of the proposed method. PMID- 20303079 TI - Pronation and supination after forearm fractures in children: Reliability of visual estimation and conventional goniometry measurement. AB - BACKGROUND: Forearm fractures are common amongst children and often result in limited rotational function. In daily practice, pronation and supination of the arm are often visually estimated or measured using a conventional goniometer. The aim of this study was to compare the reliability of these two methods in paediatric patients who had previously sustained a forearm fracture. METHODS: Intra- and interrater reliability of visual estimation and conventional goniometry were determined in 47 children who had previously sustained a forearm fracture. RESULTS: Intra- and interrater reliability of visual estimation and conventional goniometry was fair to excellent, with intraclass correlation coefficients (ICCs) ranging between 0.75 and 0.94. In addition, the overall goniometer data consistently showed lower smallest detectable differences (SDDs) compared to the visual estimation data, also indicating better reliability for the goniometer method. CONCLUSIONS: A conventional goniometer is an easy, fast and reliable method to determine the pronation and supination in a child who had sustained a forearm fracture. If an uncooperative child hinders the measurement, visual estimation is a good second choice. Measurements are more reliable when repeated by the same professional. PMID- 20303080 TI - Patient perceptions of nurse-delivered cardiovascular prevention: cross-sectional survey within a randomised trial. AB - BACKGROUND: Studies have shown that in general patients are positive about cardiovascular prevention delivered by general practitioners. Further, it has been found that care by nurses for the chronically ill leads to even greater patient satisfaction. OBJECTIVE: The aim of this survey was to answer the following questions: How do patients perceive cardiovascular prevention delivered by the practice nurse? Are patient characteristics and personal health status associated with experiences of received nurse-led care? DESIGN: A cross-sectional survey after completion of a randomised trial. SETTING: Six primary health care centres in the Netherlands (25 general practitioners, 6 practice nurses, 30,000 patients). PARTICIPANTS: Included in the randomised trial were 701 patients with at least a 10% risk of fatal cardiovascular disease within 10 years. Patients who visited a cardiovascular specialist more often than once a year and patients with diabetes were excluded from the study. In 90% of the patients it concerned secondary prevention. Half of the patients received nurse-delivered care and half received care by the general practitioner. METHOD: A questionnaire was sent by post to all patients after having received one year of cardiovascular prevention. A dual moderator focus group study was held for the development of the questionnaire. FINDINGS: The response rate was 69%. Patients were more satisfied with nurse-delivered cardiovascular prevention compared to standard care by general practitioners. The majority of patients agreed with positive statements regarding received nurse-led care. Patient characteristics such as age, educational level and gender were significantly associated with patients experiences. Furthermore, a significant association between experiences and personal health status was found. In comparison with patients who did not smoke, smokers would recommend the practice nurse less to others (X(2)=4.0, p=0.047), felt more 'rapped on their knuckles' (X(2)=11.5, p=0.003), found the consultation more 'awkward' (X(2)=8.3, p=0.016) and thought the nurse less understanding of their personal situation (X(2)=6.4, p=0.041) and less able to explain clearly (X(2)=6.5, p=0.039). CONCLUSIONS: The majority of patients responded positively to nurse-delivered cardiovascular prevention. Further improvement could be gained by paying more attention to motivational interviewing. Nurses should approach high risk patients more specifically according to the type of risk factor to be treated. PMID- 20303081 TI - Relationship of job satisfaction with perceived organizational support and quality of care among South Korean nurses: a questionnaire survey. AB - BACKGROUND: The International Hospital Outcomes Study found that organizational/managerial support for nursing has a pronounced effect on nurses' job dissatisfaction, burnout and quality of care. However, these findings have not been validated in non-Western countries using the same study method and instrument. OBJECTIVES: The objectives of this study were to: (a) examine associations between job satisfaction and burnout, organizational support and quality of care reported by South Korean nurses, (b) identify the best predictors of job satisfaction among South Korean nurses through multivariate modeling and (c) compare findings of this study with those from the International Hospital Outcomes Study. RESEARCH METHOD: This replication study used a cross-sectional survey design. The Pennsylvania Registered Nurse Survey used in the International Hospital Outcomes Study (IHOS) was administered to 496 registered nurses working at 23 acute hospitals in South Korea. A statistical model of job satisfaction was developed using logistic regression. RESULTS: Job dissatisfaction was positively correlated to total burnout scores (r=.42, p<.001) and lack of organizational support (r=.36, p<.001). Multivariate analysis found that job satisfaction was significantly associated at the level of 0.05 with total burnout scores, amount of organizational support and satisfaction with nurse identity, with odds ratios of .92 (p<.001), 1.04 (p<.01) and 11.93 (p<.001), respectively. Korean nurses reported low quality of care in their practice setting and were less confident in their patients' ability of self-management after discharge. Yet despite a high patient-to-nurse ratio (22 patients per nurse), Korean nurses had a higher job satisfaction rate (68.8%) and lower burnout scores (35.7) than their counterparts in the International Hospital Outcomes Study. CONCLUSION: The high patient-to nurse ratio allows South Korean nurses to focus on more technical tasks that give less stress and have higher job satisfaction because of it. However, this also leads to the South Korean nurses having less confidence in their patient's ability to take care of themselves upon discharge. South Korean nurses should also be given opportunity to advance themselves professionally and be recognized for their abilities while being given more responsibility for the clinical decision making in their patient's care. PMID- 20303084 TI - Transdifferentiation of bone marrow-derived endothelial progenitor cells into the smooth muscle cell lineage mediated by tansforming growth factor-beta1. AB - OBJECTIVE: The aim of this study was to investigate the transdifferentiation of bone marrow (BM)-derived endothelial progenitor cells (EPCs) into the smooth muscle cell (SMC) lineage in vitro and in vivo. METHODS AND RESULTS: EPCs were obtained from BM of rats and cultured on fibronectin-coated dishes for 15 days. Treatment of EPCs with transforming growth factor (TGF)-beta1 for 7 days changed morphology of EPCs, reduced the expression of endothelial markers in EPCs, induced the expression of SMC markers, and enhanced their proliferation. EPCs expressed TGF-beta receptor type II (TGF-beta RII) and TGF-beta1 induced the phosphorylation of Smad 2 in EPCs. TGF-beta1-induced transdifferentiation was specifically inhibited by neutralizing antibody against TGF-beta and gene silencing of TGF-beta RII. Local transplantation of autologous EPCs enhanced intimal hyperplasia of the balloon-injured artery on day 28. Transplanted EPCs were localized near the endothelial layer on day 14 but widely distributed within the hypertrophic neointima on day 28 differentiating toward SMC lineage. Neither expression of growth factors such as TGF-beta1 nor early inflammatory reactions within the denuded arteries were promoted by transplantation of EPCs. CONCLUSIONS: TGF-beta1 induced the transdifferentiation of BM-derived EPCs toward SMC lineage mediated by TGF-beta RII. The augmentation of intimal hyperplasia by transplantation of EPCs was probably due to the transdifferentiation and proliferation of EPCs induced by TGF-beta1. PMID- 20303085 TI - The sensitivity of endpoint forces produced by the extrinsic muscles of the thumb to posture. AB - This study utilizes a biomechanical model of the thumb to estimate the force produced at the thumb-tip by each of the four extrinsic muscles. We used the principle of virtual work to relate joint torques produced by a given muscle force to the resulting endpoint force and compared the results to two separate cadaveric studies. When we calculated thumb-tip forces using the muscle forces and thumb postures described in the experimental studies, we observed large errors. When relatively small deviations from experimentally reported thumb joint angles were allowed, errors in force direction decreased substantially. For example, when thumb posture was constrained to fall within +/-15 degrees of reported joint angles, simulated force directions fell within experimental variability in the proximal-palmar plane for all four muscles. Increasing the solution space from +/-1 degrees to an unbounded space produced a sigmoidal decrease in error in force direction. Changes in thumb posture remained consistent with a lateral pinch posture, and were generally consistent with each muscle's function. Altering thumb posture alters both the components of the Jacobian and muscle moment arms in a nonlinear fashion, yielding a nonlinear change in thumb-tip force relative to muscle force. These results explain experimental data that suggest endpoint force is a nonlinear function of muscle force for the thumb, support the continued use of methods that implement linear transformations between muscle force and thumb-tip force for a specific posture, and suggest the feasibility of accurate prediction of lateral pinch force in situations where joint angles can be measured accurately. PMID- 20303086 TI - Determination of pharmaceuticals in environmental and biological matrices using pressurised liquid extraction--are we developing sound extraction methods? AB - Pressurised liquid extraction (PLE) is now a well established and extensively applied extraction technique in environmental analysis for pollutants such as persistent organic pollutants (POPs). During the past decade, an emerging group of environmentally interesting analytes are pharmaceuticals that are continuingly released into the environment. This class is comprised with compounds of various properties. As the field of the analysis of these compounds grows, an increasing number of PLE methods for pharmaceuticals of varying quality are developed and published. This review summarises the critical PLE parameters during PLE method development and highlight them with examples from recently published papers utilising pressurised liquid extraction for the determination of pharmaceuticals in environmental and biological matrices. These recent methods are summarised and critically discussed with the aim to provide important reflections to alleviate in future PLE development for pharmaceuticals in environmental matrices. PMID- 20303087 TI - Separation of alkanes and aromatic compounds by packed column gas chromatography using functionalized multi-walled carbon nanotubes as stationary phases. AB - In the present work, we show a novel application of pristine and functionalized Multi-Walled Carbon Nanotubes (MWCNTs) as stationary phase in low-cost packed columns for the gas chromatographic separation of alkanes and aromatic hydrocarbons. The MWCNTs were deeply investigated by means of physical and chemical methods, like thermal analysis, IR and atomic force microscopy, and Inverse Gas Chromatography (IGC) in order to correlate the adsorption process and surface properties with the material purity level and functionalization degree. The derivatization process of the pristine nanotubes was a key factor to achieve a successful separation of both the light n-alkanes (C3-C5) and the related isomers (C4-C5 branched alkanes). Satisfactory results were similarly obtained in the case of separation of aromatic hydrocarbons (BTX). PMID- 20303088 TI - Weak anion-exchange hypercrosslinked sorbent in on-line solid-phase extraction liquid chromatography coupling to achieve automated determination with an effective clean-up. AB - A mixed-mode polymeric sorbent was on-line coupled to liquid chromatography (LC) for the first time and applied to the selective solid-phase extract a group of pharmaceuticals in complex environmental water samples. The mixed-mode polymeric sorbent is a high-specific surface area hypercrosslinked polymer resin (HXLPP) in the form of monodisperse microspheres further modified with 1,2-ethylenediamine (EDA) moieties. These properties allow its application as a weak anion-exchange (WAX) sorbent in the on-line solid-phase extraction (SPE) coupling. The on-line SPE-LC method developed using the HXLPP-WAX sorbent was successfully applied to percolate a large volume of ultrapure (500 ml), river (250 ml) and effluent sewage (100 ml) water samples. In all the cases, the HXLPP-WAX resin provided near total recoveries of the most acidic compounds studied and clean chromatograms. This is because the ion-exchange interactions enable a washing step to be added to the SPE protocol that removes the compounds with weak acidic, neutral and basic properties from the sample matrix. PMID- 20303089 TI - Application of high performance liquid chromatography coupled to on-line solid phase extraction-nuclear magnetic resonance spectroscopy for the analysis of degradation products of V-class nerve agents and nitrogen mustard. AB - The detection and identification of the degradation products of nitrogen mustard and nerve agent VX by high performance liquid chromatography coupled to on-line solid-phase extraction-nuclear magnetic resonance spectroscopy (HPLC-UV-SPE-NMR) were demonstrated. The analytes selected for the study were N,N dimethylaminoethanol (DMAE), N,N-diethylaminoethanol (DEAE), N,N diisopropylaminoethanol (DIAE) and triethanolamine (TEA). Offline solid-phase extraction (SPE) followed by derivatization was applied to eliminate the interferents and make the analytes amenable for UV detection. Thereafter, chromatographically separated derivatives were trapped on on-line SPE cartridges. They were subsequently eluted and 1H NMR and COSY spectra were obtained. The overall detection limits of the LC-UV-SPE-NMR method for the mentioned analytes were found to be 18, 23, 25, and 32 mg/L respectively. Applicability of the method to real samples was demonstrated by the analysis of samples provided during the 22nd OPCW official proficiency test. The method gave reproducible NMR spectra devoid of intense background signals. PMID- 20303090 TI - Basic rules for the interpretation of atmospheric pressure ionization mass spectra of small molecules. AB - This review summarizes the basic rules for the interpretation of atmospheric pressure ionization (API) mass spectra of small molecules written with the style primarily intended for beginners and low-experienced researchers with the mass spectra interpretation. The first and basic step in any interpretation of mass spectra is always the determination of molecular weight, which is relatively easy in case of soft ionization techniques due to the limited extend of fragmentation and the prevailing presence of (de)protonated molecules in the full scan mass spectra. These [M+H](+) and [M-H](-) ions are often accompanied by low abundant molecular adducts, which can be used as the supplementary information for the unambiguous determination of molecular weights. In certain cases, adduct ions may dominate the spectra. The subsequent interpretation of full scan and tandem mass spectra is more complicated due to a high number of possible functional groups, structural subunits and their combinations resulting in numerous competitive fragmentation pathways. Typical neutral losses and the effect of individual functional groups on the fragmentation are discussed in detail and illustrated with selected examples. Modern mass analyzers have powerful features for the structural elucidation, for example high resolving power, high mass accuracy, multistage tandem mass spectrometry, dedicated softwares for the interpretation of mass spectra and prediction of their fragmentation. Background information on differences among individual ionization techniques suitable for the HPLC-MS coupling and basic types of mass analyzers with consequences for the data interpretation is briefly discussed as well. Selected examples illustrate that the right optimization of chromatographic separation and the use of other than mass spectrometric detectors can bring valuable complementary information. PMID- 20303091 TI - Separation of structurally similar nocathiacin analogues by reversed phase chromatography. AB - The complete separation of structurally similar compounds has been a challenge due mainly to their similarity on physical and chemical properties. In the present study, a simple and effective chromatographic method to separate and purify nocathiacin acid from its structural analogue nocathiacin I was developed. After evaluating mobile phase compositions on the retention characteristics by reversed phase high-performance liquid chromatography (HPLC), the elution order of nocathiacin I and nocathiacin acid was completely reversed, and the resolution value between the two analogues was improved, by varying pH value and ionic strength, to greater than 10 from merged peaks under initial conditions. In addition, a preparative isolation of nocathiacin acid was performed by reversed phase column chromatography under the guidance of the HPLC study. This chromatographic method resulted in an efficient process to obtain pure nocathiacin acid with a recovery rate of 83%. The present approach offers a new methodology for the separation of structurally closely related secondary metabolites. PMID- 20303092 TI - Development of a simple extraction and clean-up procedure for determination of organochlorine pesticides in soil using gas chromatography-tandem mass spectrometry. AB - A procedure based on QuEChERS extraction and a simultaneous liquid-liquid partition clean-up was developed. The procedure involved extraction of hydrated soil samples using acetonitrile and clean-up by liquid-liquid partition into n hexane. The hexane extracts produced were clean and suitable for determination using gas chromatography-tandem mass spectrometry (GC-MS/MS). The method was validated by analysis of soil samples, spiked at five levels between 1 and 200 microg kg(-1). The recovery values were generally between 70 and 100% and the relative standard deviation values (%RSDs) were at or below 20%. The procedure was validated for determination of 19 organochlorine (OC) pesticides. These were hexachlorobenzene (HCB), alpha-HCH, beta-HCH, gamma-HCH, heptachlor, heptachlor epoxide (trans), aldrin, dieldrin, chlordane (trans), chlordane (cis), oxychlordane, alpha-endosulfan, beta-endosulfan, endosulfan sulfate, endrin, p,p' DDT, o,p'-DDT, p,p'-DDD and p,p'-DDE. The method achieved low limits of detection (LOD; typically 0.3 microg kg(-1)) and low limits of quantification (LOQ; typically 1.0 microg kg(-1)). The method performance was also assessed using five fortified soil samples with different physico-chemical properties and the method performance was consistent for the different types of soil samples. The proposed method was compared with an established procedure based on Soxtec extraction. This comparison was carried out using six soil samples collected from regions of Pakistan with a history of intensive pesticide use. The results of this comparison showed that the two procedures produced results with good agreement. The proposed method produced cleaner extracts and therefore led to lower limits of quantification. The proposed method was less time consuming and safer to use. The six samples tested during this comparison showed that soils from cotton growing regions contained a number of persistent OC residues at relatively low levels (<10 microg kg(-1)). These residues were alpha-HCH, gamma-HCH, heptachlor, chlordane (trans), p,p'-DDT, o,p'-DDT, p,p'-DDD, p,p'-DDE, beta-endosulfan and endosulfan sulfate. PMID- 20303093 TI - Determination of pesticides in seaweeds by pressurized liquid extraction and programmed temperature vaporization-based large volume injection-gas chromatography-tandem mass spectrometry. AB - A rapid method for the simultaneous identification and quantification of pesticide residues in edible seaweed has been developed. Target analytes were three pyrethroid, a carbamate and two organophosphorus pesticides. The procedure consists of a pressurized liquid extraction (PLE) with integrated clean-up, followed by gas chromatography coupled to tandem mass spectrometry. Five PLE parameters were investigated using a screening design: temperature, static extraction time, number of cycles, percent of flush volume and quantitative composition of the n-hexane/ethyl acetate extraction solvent. The effect of the in-cell clean-up with Florisil and graphitized carbon black adsorbents was investigated using a Doehlert response surface design. Large volumes of sample extracts were injected using a programmed-temperature vaporizer (PTV-LVI) to improve both sensitivity and selectivity of measurements. Quantification was carried by the internal standard method with surrogate deuterated standards. The method showed excellent linearity (R2>0.999) and precision (relative standard deviation, RSD < or = 8%) for all compounds, with detection limits ranging from 0.3 pg g(-1) for chlorpyrifos-ethyl, to 3.0 pg g(-1) for carbaryl (23.1 pg g(-1) for deltamethrin). Recoveries in real seaweed samples were within the range 82 108%. The method was satisfactory validated for the analysis of wild and cultivated edible seaweeds. The presence of pyrethroid and organophosphorus pesticides in some of the samples was evidenced. PMID- 20303094 TI - Deformation of a long elastic particle undergoing electrophoresis. AB - The motion and deformation of a long elastic particle undergoing electrophoresis has been studied numerically and analytically. The particle is elliptical in shape and is initially aligned with its major axis perpendicular to the direction of a uniformly applied electric field. The particle tends to curl up at its ends and arches in the middle as it moves. The deformation of the particle is due to the viscous stress acting on the particle surface. The results from the simulation are explained by evaluating the surface force distribution on a long thin object under similar conditions. The pressure due to the inertia of the flow has a negligible effect on this deformation. PMID- 20303095 TI - Central nervous system findings on functional magnetic resonance imaging in patients before and after treatment with anticholinergic medication. AB - PURPOSE: Anticholinergic medications are commonly used to treat urinary urgency and frequency. Muscarinic receptors are located in areas beyond the detrusor muscle. In this study we measured changes in central nervous system activity in patients with lower urinary tract symptoms treated with tolterodine or a placebo. MATERIALS AND METHODS: A total of 20 female patients with urinary frequency were randomized to 4 weeks of treatment with tolterodine or a placebo. Functional magnetic resonance imaging based on blood oxygenation level dependant imaging of the brain during bladder filling was performed before and after treatment. For each patient the bladder was filled by a urethral catheter and emptied 5 times. RESULTS: Multiple brain areas showed significant activation with bladder filling compared to the empty state and many areas also showed deactivation. Overall brain activation with bladder filling was decreased after treatment in both groups. After treatment 2 areas of the parietal cortex (precuneus and postcentral gyrus) showed significantly greater activity in patients treated with tolterodine vs placebo. Two areas of the cerebellum (anterior lobe and culmen) showed significantly greater activity in the placebo group, and these were also areas of significant deactivation in the tolterodine group. CONCLUSIONS: Brain activity changes as well as the areas of activation after treatment of lower urinary tract symptoms in patients with an anticholinergic medication or placebo are different in the 2 groups. Whether this finding represents action at the central nervous system or the bladder level is not known. PMID- 20303096 TI - The inadequacy of urinary dipstick and microscopy as surrogate markers of urinary tract infection in urological outpatients with lower urinary tract symptoms without acute frequency and dysuria. AB - PURPOSE: Diagnosing urinary infection in patients with chronic lower urinary tract symptoms without dysuria is a critical step. In this study we scrutinize the sensitivity and specificity of dipstick urinalysis and microscopic pyuria (10 or more white blood cells per microl) to identify infection in such patients. MATERIALS AND METHODS: This was a prospective, blinded, observational cohort study of urological outpatients with painless lower urinary tract symptoms. Midstream and catheter urine samples were analyzed. A total of 508 midstream urine samples were used to compare leukocyte esterase, nitrite dipstick and urine microscopy with cultures seeking 10(5) cfu/ml. Similarly 470 catheter urine samples were used to compare the same surrogates with 10(5) cfu/ml and with an enhanced culture method seeking 10(2) cfu/ml. A comparison of leukocyte esterase against microscopic pyuria was made using the 508 midstream and 470 catheter specimens of urine. Midstream urine specimens were provided by 42 normal volunteers for comparison. RESULTS: For a midstream urine culture at 10(5) cfu/ml leukocyte esterase was 56% sensitive, nitrite was 10% sensitive and microscopic pyuria was 56% sensitive. Specificities were 66%, 99% and 72%, respectively. For a catheter specimen of urine culture at 10(5) cfu/ml leukocyte esterase was 59% sensitive, nitrite was 20% sensitive and microscopic pyuria was 66% sensitive. Specificities were 84%, 97% and 73%, respectively. The enhanced culture of catheter specimen of urine at 10(2) cfu/ml was positive in 29% of patients vs 15% at 10(5) cfu/ml. CONCLUSIONS: Despite official guidelines and widespread use these tests cannot be considered appropriate for diagnosing urinary tract infection in patients with lower urinary tract symptoms, and should be abandoned in this context. PMID- 20303097 TI - The relationship between children with voiding problems and their parents. AB - PURPOSE: We determined whether parents of children with overactive bladder and dysfunctional voiding had had similar symptoms in childhood. MATERIALS AND METHODS: A case-control study was done in parents with and without children with overactive bladder or dysfunctional voiding. All were recruited from an outpatient clinic. Diagnoses in children were made according to the International Children's Continence Society standardization report. Childhood symptoms in parents were assessed by a 19-item questionnaire and current urogenital symptoms were assessed by the Urogenital Distress Inventory. Comparisons between groups were made with categorical and interval statistics. RESULTS: A total of 173 cases and 98 controls were entered in the study. Statistically significantly more mothers of children with overactive bladder or dysfunctional voiding reported having had similar symptoms in childhood than mothers of children without lower urinary tract symptoms. Overactive bladder symptoms of childhood persisted into adulthood. No association between childhood dysfunctional voiding symptoms and adult emptying disorders was noted. Fathers of children with overactive bladder reported to have stopped bed-wetting at a significantly later age than control fathers. CONCLUSIONS: Results reveal an association between overactive bladder symptoms in children and their parents. To a lesser extent this finding also holds true for dysfunctional voiding symptoms. PMID- 20303098 TI - Urethroplasty with abdominal skin grafts for long segment urethral strictures. AB - PURPOSE: Buccal derived graft tissue has been proven to be useful in urethral reconstruction. However, nonbuccal sources are often needed for long segment strictures or for those with prior buccal harvest. We describe a technique using full-thickness abdominal skin grafts for long segment urethroplasty and present the short-term outcomes. MATERIALS AND METHODS: A total of 21 men underwent urethroplasty for strictures of an average of 11 cm (range 4 to 24) using abdominal wall skin. Prior urethroplasty was performed in 52% of patients and multistage repair was conducted in 48%. RESULTS: The recurrence rate following urethroplasty was 19%, with 9.5% requiring revision after first stage urethroplasty. Complications included hair from the skin graft during the early part of the series (14.5%), glans dehiscence (9.5%), urethrocutaneous fistula (9.5%) and periurethral abscess (1 patient). Histological evaluation at 6 months demonstrated excellent uptake of grafts with minimal keratinization. CONCLUSIONS: In men with significant penile scarring, lichen sclerosis and long segment urethral strictures the use of abdominal skin limits donor site morbidity, and provides a useful alternative graft source for urethroplasty when buccal mucosa or genital skin are not available or sufficient. Grafts should be harvested from nonhair bearing areas to minimize the risk of urethral hair development. PMID- 20303099 TI - Development, validation and testing of an epidemiological case definition of interstitial cystitis/painful bladder syndrome. AB - PURPOSE: No standard case definition exists for interstitial cystitis/painful bladder syndrome for patient screening or epidemiological studies. As part of the RAND Interstitial Cystitis Epidemiology study, we developed a case definition for interstitial cystitis/painful bladder syndrome with known sensitivity and specificity. We compared this definition with others used in interstitial cystitis/painful bladder syndrome epidemiological studies. MATERIALS AND METHODS: We reviewed the literature and performed a structured, expert panel process to arrive at an interstitial cystitis/painful bladder syndrome case definition. We developed a questionnaire to assess interstitial cystitis/painful bladder syndrome symptoms using this case definition and others used in the literature. We administered the questionnaire to 599 women with interstitial cystitis/painful bladder syndrome, overactive bladder, endometriosis or vulvodynia. The sensitivity and specificity of each definition was calculated using physician assigned diagnoses as the reference standard. RESULTS: No single epidemiological definition had high sensitivity and high specificity. Thus, 2 definitions were developed. One had high sensitivity (81%) and low specificity (54%), and the other had the converse (48% sensitivity and 83% specificity). These values were comparable or superior to those of other epidemiological definitions used in interstitial cystitis/painful bladder syndrome prevalence studies. CONCLUSIONS: No single case definition of interstitial cystitis/painful bladder syndrome provides high sensitivity and high specificity to identify the condition. For prevalence studies of interstitial cystitis/painful bladder syndrome the best approach may be to use 2 definitions that would yield a prevalence range. The RAND Interstitial Cystitis Epidemiology interstitial cystitis/painful bladder syndrome case definitions, developed through structured consensus and validation, can be used for this purpose. PMID- 20303100 TI - Quality of life after open or robotic prostatectomy, cryoablation or brachytherapy for localized prostate cancer. AB - PURPOSE: Health related quality of life concerns factor prominently in prostate cancer management. We describe health related quality of life impact and recovery profiles of 4 commonly used operative treatments for localized prostate cancer. MATERIALS AND METHODS: Beginning in February 2000 all patients treated with open radical prostatectomy, robot assisted laparoscopic prostatectomy, brachytherapy or cryotherapy were asked to complete the UCLA-PCI questionnaire before treatment, and at 3, 6, 12, 18, 24, 30 and 36 months after treatment. Outcomes were compared across treatment types with statistical analysis using univariate and multivariate models. RESULTS: A total of 785 patients treated between February 2000 and December 2008 were included in the analysis with a mean followup of 24 months. All health related quality of life domains were adversely affected by all treatments and recovery profiles varied significantly by treatment type. Overall urinary function and bother outcomes scored significantly higher after brachytherapy and cryotherapy compared to open radical prostatectomy and robotic assisted laparoscopic radical prostatectomy. Brachytherapy and cryotherapy had a 3-fold higher rate of return to baseline urinary function compared to open radical prostatectomy and robotic assisted laparoscopic radical prostatectomy. Sexual function and bother scores were highest after brachytherapy, with a 5-fold higher rate of return to baseline function compared to cryotherapy, open radical prostatectomy and robotic assisted laparoscopic radical prostatectomy. All 4 treatments were associated with relatively transient and less pronounced impact on bowel function and bother. CONCLUSIONS: In a study of sequential health related quality of life assessments brachytherapy and cryotherapy were associated with higher urinary function and bother scores compared to open radical prostatectomy and da Vinci prostatectomy. Brachytherapy was associated with higher sexual function and bother scores compared to open radical prostatectomy, robotic assisted laparoscopic radical prostatectomy and cryotherapy. PMID- 20303101 TI - Progression of lower urinary tract symptoms in older men: a community based study. AB - PURPOSE: Lower urinary tract symptom progression in community dwelling older men is not well described. MATERIALS AND METHODS: We evaluated 5,697 participants in Osteoporotic Fractures in Men, a prospective cohort study of community dwelling men 65 years old or older. We characterized lower urinary tract symptoms using the American Urological Association symptom index at 2 time points, including at study entry and at 2-year followup. Progression was examined in the overall cohort and within baseline symptom strata (symptom index 7 or less and 8 or greater) using descriptive statistics. RESULTS: At baseline mean +/- SD age was 73.5 +/- 5.8 years and mean symptom index score was 8.3 +/- 6.3 points. Mean and median total symptom index increased during followup by 1.1 +/- 5.0 and 1.0 points, respectively. Of the 3,092 men with a symptom index of 7 points or less at baseline 883 (29%) reported lower urinary tract symptoms progression (8 points or greater) at followup. The incidence of lower urinary tract symptom progression increased with advancing baseline age. Of the 2,605 men with a symptom index of 8 points or greater at baseline 622 (24%) reported progression of at least 4 points at followup. Of the 2,200 men with a baseline symptom index of 7 points or less and no history of benign prostatic hyperplasia or lower urinary tract symptom treatment 94% remained untreated, 2% reported benign prostatic hyperplasia surgery and 4% reported medication use at followup. CONCLUSIONS: Up to 29% of community dwelling older men with no or mild lower urinary tract symptoms will have clinically significant lower urinary tract symptoms within 2 years. These data help elucidate the natural history of lower urinary tract symptoms in the community and provide useful data to design clinical trials of lower urinary tract symptom prevention. PMID- 20303103 TI - Tumor volume in radical prostatectomy specimens assessed by digital image analysis software correlates with other prognostic factors. AB - PURPOSE: Digital image analysis software to review histopathology specimens is advancing uropathology by objectivity and reproducibility. Subjective pathologist assessed prostate tumor volume calculations correlate with known prognostic factors at radical prostatectomy. We ascertained whether image analysis software calculations of prostate tumor volume correlate with such prognostic factors, particularly positive surgical margins. MATERIALS AND METHODS: Prostate tumor volume was calculated using digital image analysis software in 851 sequential radical prostatectomy specimens. Results were correlated with clinicopathological data by logistic regression. RESULTS: Median prostate tumor volume was 2.2 cc (IQR 0.9-3.8). Median peripheral and transition zone tumor volume was 1.9 and 0.6 cc, respectively. Transition zone tumors were noted in 236 specimens (27.8%) and positive surgical margins occurred in 244 (28.7%). Tumors with extensive positive surgical margins had larger image analysis software assessed prostate tumor volume (p = 0.029) and peripheral zone volume (p = 0.007) than those with only focal positive surgical margins. On univariate analysis positive surgical margin tumors were larger and had seminal vesicle invasion, extraprostatic extension, perineural invasion and higher preoperative prostate specific antigen than those without positive surgical margins (each p <0.001). A linear relationship existed between image analysis software determined prostate tumor volume, and increasing tumor stage, Gleason score and prostate specific antigen (p for trend <0.001). On multivariate analysis tumor volume and tumor volume as a percent of prostate volume predicted positive surgical margins. CONCLUSIONS: Prostate tumor volume determined objectively by image analysis software correlates with positive surgical margins, as do prognostic variables such as extraprostatic extension, seminal vesicle invasion, perineural invasion, peripheral zone volume and Gleason score greater than 7. Objective digital image analysis software assessment appears to be a valid form to determine prostate tumor volume at radical prostatectomy. It is a useful adjunct to other histopathological analyses. PMID- 20303102 TI - Update of AUA guideline on the surgical management of female stress urinary incontinence. AB - PURPOSE: We updated the 1997 American Urological Association guideline on female stress incontinence. MATERIALS AND METHODS: MEDLINE searches of English language publications from 1994 and new searches of the literature published between December 2002 and June 2005 were performed using identified MeSH terms. Articles were selected for the index patient defined as the otherwise healthy woman who elected to undergo surgery to correct stress urinary incontinence or the otherwise healthy woman with incontinence and prolapse who elected to undergo treatment for both conditions. RESULTS: A total of 436 articles were identified as suitable for inclusion in the meta-analysis, and an additional 155 articles were suitable for complications data only due to insufficient followup of efficacy outcomes in the latter reports. Surgical efficacy was defined using outcomes pre-specified in the primary evidence articles. Urgency (resolution and de novo) was included as an efficacy outcome due to its significant impact on quality of life. The primary efficacy outcome was resolution of stress incontinence measured as completely dry (cured/dry) or improved (cured/improved). Complications were analyzed similarly to the efficacy outcomes. Subjective complications (pain, sexual dysfunction and voiding dysfunction) were also included as a separate category. CONCLUSIONS: The surgical management of stress urinary incontinence with or without combined prolapse treatment continues to evolve. New technologies have emerged which have impacted surgical treatment algorithms. Cystoscopy has been added as a standard component of the procedure during surgical implantation of slings. PMID- 20303105 TI - Editorial comment. PMID- 20303104 TI - Preoperative prostate specific antigen doubling time is not a useful predictor of biochemical progression after radical prostatectomy. AB - PURPOSE: Postoperative prostate specific antigen doubling time may be used as a surrogate for prostate cancer specific mortality in patients with biochemical recurrence after radical prostatectomy. Less is known about the usefulness of preoperative prostate specific antigen doubling time for the initial prediction of prostatectomy outcomes. MATERIALS AND METHODS: Preoperative prostate specific antigen doubling time was calculated in 1,208 men from a large prostate cancer screening study who were treated with radical prostatectomy. We examined the relationship of prostate specific antigen doubling time with tumor features and biochemical progression-free survival. RESULTS: Overall prostate specific antigen doubling time was associated with nonorgan confined disease (OR 0.996, 95% CI 0.992-0.999, p = 0.013) but not with biochemical progression (HR 1.000, 95% CI 0.998-1.001, p = 0.66). Using previously published 18 and 36-month thresholds for prostate specific antigen doubling time there was no significant relationship between doubling time and specific adverse pathological features or biochemical progression. Using the concordance index prostate specific antigen doubling time did not enhance the prediction of biochemical progression beyond that achieved by a model with prostate specific antigen, clinical stage and biopsy Gleason score. CONCLUSIONS: In our series of men with newly diagnosed, clinically localized prostate cancer shorter preoperative prostate specific antigen doubling time was associated with nonorgan confined disease but not with biochemical progression after radical prostatectomy. All calculations of prostate specific antigen kinetics may not be equivalent. Caution should be exercised when using prostate specific antigen doubling time in the pretreatment setting. PMID- 20303106 TI - Editorial comment. PMID- 20303107 TI - Advanced penile verrucous carcinoma treated with intra-aortic infusion chemotherapy. AB - PURPOSE: Traditional treatment for advanced penile verrucous carcinoma is penectomy. This mostly leads to remarkable psychosexual problems and greatly affects quality of life, especially in young patients. To preserve the penis we used intra-aortic infusion chemotherapy for advanced verrucous carcinoma. MATERIALS AND METHODS: From 1991 to 2009 we treated 6 men with penile verrucous carcinoma with continuous intra-aortic infusion of 50 mg methotrexate every 24 hours (average 550 mg, range 400 to 800). Citrovorum factor (6 mg) was given intramuscularly every 6 hours during methotrexate infusion. After continuous methotrexate infusion no further anticancer drug was given to complete responders. Partial responders subsequently received long-term, intermittent, intra-aortic infusion of 50 mg methotrexate or 2 mg mitomycin C plus 250 mg 5 fluorouracil every 1 to 2 weeks until tumors disappeared and all wounds healed. RESULTS: After treatment 4 patients achieved a complete response and were disease free 3 years 9 months to 17 years 10 months (median 11 years 3 months) after therapy. Two patients had a partial response. The patient with a shaft tumor subsequently underwent total penectomy due to unbearable penile pain 4 years after infusion with various drugs without an appreciable response. He has survived 12 years 5 months after initial treatment. The other patient with glans and prepuce tumors had progression with bilateral inguinal metastases despite 1 1/2 years of infusion therapy. Total penectomy was done. Histological examination of the glans mass revealed moderately differentiated squamous cell carcinoma. Patient condition progressed rapidly and he died 11 months after penectomy. CONCLUSIONS: Intra-aortic infusion chemotherapy is a simple, effective method to treat penile verrucous carcinoma with the uniqueness of preserving the anatomical structure and sexual function in complete responders. For penile verrucous carcinoma, especially in younger patients, intra-aortic infusion chemotherapy may be considered organ sparing treatment before penectomy. PMID- 20303108 TI - Initial experience with 50 laparoendoscopic single site surgeries using a homemade, single port device at a single center. AB - PURPOSE: We report our technique of and initial experience with 50 patients who underwent laparoendoscopic single site surgery using a homemade single port device at a single institution. MATERIALS AND METHODS: Between December 2008 and August 2009 we performed 50 laparoendoscopic single site surgeries using the Alexis wound retractor, which was inserted at the umbilical incision. A homemade single port device was made by fixing a size 7 1/2 surgical glove to the retractor outer ring and securing the glove fingers to the end of 3 or 4 trocars with a tie and a rubber band. A prospective study was performed in 50 patients to evaluate outcomes. RESULTS: Of 50 patients 34 underwent conventional laparoendoscopic single site surgery, including radical and simple nephrectomy, and cyst decortication in 8 each, nephroureterectomy in 3, partial nephrectomy and adrenalectomy in 2 each, and partial cystectomy, ureterectomy and ureterolithotomy in 1 each, while 16 underwent robotic laparoendoscopic single site surgery, including partial nephrectomy in 11, nephroureterectomy in 3, and simple and radical nephrectomy in 1 each. Mean patient age was 52 years, mean body mass index was 23.4 kg/m(2), mean operative time was 201 minutes and mean estimated blood loss was 201 ml. Four intraoperative complications occurred, including 2 bowel serosal tears, diaphragm partial tearing and conversion to open radical nephrectomy. One case of postoperative bleeding was managed by transfusion. Surgical margins were negative in the 13 patients who underwent partial nephrectomy. Mean hospital stay was 4.5 days (range 1 to 16). CONCLUSIONS: Our homemade single port device is cost-effective, provides adequate range of motion and is more flexible in port placement for laparoendoscopic single site surgery than the current multichannel port. PMID- 20303109 TI - Editorial comment. PMID- 20303110 TI - Urethrotomy has a much lower success rate than previously reported. AB - PURPOSE: We evaluated the success rate of direct vision internal urethrotomy as a treatment for simple male urethral strictures. MATERIALS AND METHODS: A retrospective chart review was performed on 136 patients who underwent urethrotomy from January 1994 through March 2009. The Kaplan-Meier method was used to analyze stricture-free probability after the first, second, third, fourth and fifth urethrotomy. Patients with complex strictures (36) were excluded from the study for reasons including previous urethroplasty, neophallus or previous radiation, and 24 patients were lost to followup. RESULTS: Data were available for 76 patients. The stricture-free rate after the first urethrotomy was 8% with a median time to recurrence of 7 months. For the second urethrotomy stricture free rate was 6% with a median time to recurrence of 9 months. For the third urethrotomy stricture-free rate was 9% with a median time to recurrence of 3 months. For procedures 4 and 5 stricture-free rate was 0% with a median time to recurrence of 20 and 8 months, respectively. CONCLUSIONS: Urethrotomy is a popular treatment for male urethral strictures. However, the performance characteristics are poor. Success rates were no higher than 9% in this series for first or subsequent urethrotomy during the observation period. Most of the patients in this series will be expected to experience failure with longer followup and the expected long-term success rate from any (1 through 5) urethrotomy approach is 0%. Urethrotomy should be considered a temporizing measure until definitive curative reconstruction can be planned. PMID- 20303111 TI - Editorial comment. PMID- 20303112 TI - Editorial comment. PMID- 20303114 TI - Experience with 750 consecutive laparoscopic donor nephrectomies--is it time to use a standardized classification of complications? AB - PURPOSE: Laparoscopic living donor nephrectomy offers patients the benefits of decreased morbidity and improved cosmesis, while maintaining equivalent graft outcomes and complication rates similar to those of open donor surgery. With expressed concern for donor safety, using a standardized complication scale would allow combining data in a donor registry so potential donors could be adequately followed and counseled. We present the largest series to our knowledge of laparoscopic living donor nephrectomy by a single surgeon. MATERIALS AND METHODS: The institution's initial 750 laparoscopic living donor nephrectomies were included in the study, and a retrospective and prospective chart and database analysis was performed. RESULTS: Mean donor age was 40.5 years and average body mass index was 25.7 kg/m(2). There were 175 patients (23%) with 2 or more renal arteries while 161 (21.5%) had early arterial bifurcations. There were 3 open conversions (0.4%) and the overall complication rate was 5.46%. Median hospital stay was 1 day and the readmission rate was 1.2%. There were 5 reoperations (0.67%), none of which was for the control of bleeding. No patients required a blood transfusion and there were no mortalities. Using a modified Clavien classification of complications for living donor nephrectomy 65.8% were grade 1, 31.7% grade 2 (12.2% grade 2a, 14.6% grade 2b, 4.9% grade 2c) and 2.4% grade 3. There were no grade 4 complications. CONCLUSIONS: With appropriate patient selection and operative experience, laparoscopic living donor nephrectomy is a safe procedure associated with low morbidity. The use of a standardized complication system specific for this procedure is encouraged and could aid in counseling potential donors in the future. PMID- 20303116 TI - Spiral multidetector computerized tomography evaluation of adjustable continence therapy implants. AB - PURPOSE: ProACT is an adjustable continence therapy implant for post prostatectomy incontinence. We evaluated the exact device location in clinical success and failed implant cases using spiral multidetector computerized tomography. MATERIALS AND METHODS: We evaluated 18 consecutive patients postoperatively using pelvic spiral multidetector computerized tomography. Of the patients 11 (61%) were dry or improved and 7 (39%) had not improved despite multiple balloon adjustments. Thin pelvic collimated scans with bone algorithm were obtained, completed by multiplanar reformatting and a volume rendering technique. The computerized tomography technique is described. RESULTS: Multidetector computerized tomography showed device sites compared to local anatomical structures. In 64% of dry or improved patients the devices were above the urogenital diaphragm and adjacent to the urethral wall (the correct position) while in the remaining 36% of cured patients only 1 device was positioned correctly. Of nonimproved patients 86% had balloons that were not adjacent to the urethra. The scout view did not show malpositioning in any of these cases. Only multiplanar reformatting with the volume rendering technique revealed misplacement. CONCLUSIONS: Multidetector computerized tomography data shows that a poor outcome in most failed cases results from poor device positioning. In a few failed cases an unsuccessful result is probably caused by excessive tissue sclerosis. To our knowledge we report for the first time how continence can be determined by the action of only 1 device. PMID- 20303117 TI - Editorial comment. PMID- 20303115 TI - Effect of amitriptyline on symptoms in treatment naive patients with interstitial cystitis/painful bladder syndrome. AB - PURPOSE: Amitriptyline is frequently used to treat patients with interstitial cystitis/painful bladder syndrome. The evidence to support this practice is derived mainly from a small, single site clinical trial and case reports. MATERIALS AND METHODS: We conducted a multicenter, randomized, double-blind, placebo controlled clinical trial of amitriptyline in subjects with interstitial cystitis/painful bladder syndrome who were naive to therapy. Study participants in both treatment arms received a standardized education and behavioral modification program. The drug dose was increased during a 6-week period from 10 up to 75 mg once daily. The primary outcome was a patient reported global response assessment of symptom improvement evaluated after 12 weeks of treatment. RESULTS: A total of 271 subjects were randomized and 231 (85%) provided a global response assessment at 12 weeks of followup. Study participants were primarily women (83%) and white (74%), with a median age of 38 years. In an intent to treat analysis (271) the rate of response of subjects reporting moderate or marked improvement from baseline in the amitriptyline and placebo groups was 55% and 45%, respectively (p = 0.12). Of the subgroup of subjects (207) who achieved a drug dose of at least 50 mg, a significantly higher response rate was observed in the amitriptyline group (66%) compared to placebo (47%) (p = 0.01). CONCLUSIONS: When all randomized subjects were considered, amitriptyline plus an education and behavioral modification program did not significantly improve symptoms in treatment naive patients with interstitial cystitis/painful bladder syndrome. However, amitriptyline may be beneficial in persons who can achieve a daily dose of 50 mg or greater, although this subgroup comparison was not specified in advance. PMID- 20303119 TI - Tolerability of 5 mg solifenacin once daily versus 5 mg oxybutynin immediate release 3 times daily: results of the VECTOR trial. AB - PURPOSE: Although antimuscarinic treatment is indicated for overactive bladder, many patients discontinue it because of dry mouth. Of available antimuscarinics oxybutynin is associated with the highest dry mouth rate. We compared the safety and tolerability of 5 mg solifenacin vs 15 mg oxybutynin immediate release. MATERIALS AND METHODS: At 12 Canadian centers a total of 132 patients with overactive bladder symptoms (greater than 1 urgency episode per 24 hours, and 8 or greater micturitions per 24 hours) were randomized to 5 mg solifenacin once daily or 5 mg oxybutynin 3 times daily for 8 weeks. The primary end point was the incidence and severity of dry mouth reported after direct questioning. Efficacy end points (3-day diary documented changes in urgency, frequency, incontinence, nocturia and voided volume), and changes on the Patient Perception of Bladder Condition scale and the Overactive Bladder Questionnaire were evaluated secondarily. RESULTS: Of patients on solifenacin vs oxybutynin immediate release 35% vs 83% reported dry mouth (p <0.0001). Of patients reporting dry mouth severity was graded moderate by 13% and 42% of those on solifenacin and oxybutynin immediate release, and severe by 13% and 28%, respectively (p = 0.001). Patients in each group showed improvements in efficacy end points, and Patient Perception of Bladder Condition scale and Overactive Bladder Questionnaire scores from baseline to treatment end. CONCLUSIONS: Significantly fewer patients on 5 mg solifenacin once daily reported dry mouth vs those receiving 5 mg oxybutynin immediate release 3 times daily. Significantly fewer patients on solifenacin reported moderate/severe dry mouth. Significantly fewer patients on solifenacin withdrew from study due to dry mouth and there were significantly fewer overall adverse events. Solifenacin and oxybutynin immediate release were efficacious in decreasing efficacy end points, and improved Patient Perception of Bladder Condition scale and Overactive Bladder Questionnaire results from baseline to treatment end. PMID- 20303120 TI - Editorial comment. PMID- 20303121 TI - [Asymptomatic Brugada syndrome unmasked by influenza virus subtype H1N1 infection]. PMID- 20303122 TI - [Comorbidity and multimorbidity indexes in the elderly patients]. AB - This article was written to reflect the importance of a correct quantification of the complexity of the elderly patient and its potential possibilities in clinical practice. From the decision to perform a laboratory test to the decision of the benefits of a determinate surgery through adjusting pathologies in several studies, most of our decisions depend on the complexity of our patients. Our decisions should be based on objective criteria that categorize the patients who may benefit from our decisions. One way is with comorbidity indexes. Another objective of this article was to review available methods to measure comorbidity and to assess its validity in the elderly. A search was made, with the keywords comorbidity, multi-morbidity and complexity associated with the elderly patient. The different methods were compared and different indexes are offered depending on our study's patients. PMID- 20303123 TI - [Harlequin syndrome]. PMID- 20303124 TI - The anorexigenic effects of metformin involve increases in hypothalamic leptin receptor expression. AB - Metformin demonstrates anorectic effects in vivo and inhibits neuropeptide Y expression in cultured hypothalamic neurons. Here we investigated the mechanisms implicated in the modulation of feeding by metformin in animals rendered obese by long-term high-fat diet (diet-induced obesity [DIO]) and in animals resistant to obesity (diet resistant [DR]). Male Long-Evans rats were kept on normal chow feeding (controls) or on high-fat diet (DIO, DR) for 6 months. Afterward, rats were treated 14 days with metformin (75 mg/kg) or isotonic sodium chloride solution and killed. Energy efficiency, metabolic parameters, and gene expression were analyzed at the end of the high-fat diet period and after 14 days of metformin treatment. At the end of the high-fat diet period, despite higher leptin levels, DIO rats had higher levels of hypothalamic neuropeptide Y expression than DR or control rats, suggesting a central leptin resistance. In DIO but also in DR rats, metformin treatment induced significant reductions of food intake accompanied by decreases in body weight. Interestingly, the weight loss achieved by metformin was correlated with pretreatment plasma leptin levels. This effect was paralleled by a stimulation of the expression of the leptin receptor gene (ObRb) in the arcuate nucleus. These data identify the hypothalamic ObRb as a gene modulated after metformin treatment and suggest that the anorectic effects of the drug are potentially mediated via an increase in the central sensitivity to leptin. Thus, they provide a rationale for novel therapeutic approaches associating leptin and metformin in the treatment of obesity. PMID- 20303125 TI - Insulin resistance and lower plasma adiponectin increase malignancy risk in nondiabetic continuous ambulatory peritoneal dialysis patients. AB - End-stage renal disease patients have a higher risk for developing cancer. Although several causes for this increased risk have been proposed, the risk factors for cancer development in this population have not been elucidated. The aim of this study was to determine whether metabolic derangements, including insulin resistance and altered adipokines, increase the risk of developing malignancies in peritoneal dialysis (PD) patients, who are vulnerable to metabolic disorders because of excessive glucose absorbed from the dialysate. Study subjects comprised 106 nondiabetic PD patients who had been on PD for a minimum of 3 months with no overt malignancy. Baseline anthropometry, fasting glucose, insulin, and adiponectin were measured. The development of malignancy was evaluated during the follow-up period. During the mean follow-up of 47.0 +/- 23.7 months, malignancy occurred in 15 patients (14.2%). The most common site of cancer was the kidney (26.7%), followed by thyroid (13.3%) and stomach (13.3%). Baseline insulin levels and homeostasis model assessment of insulin resistance were significantly higher, whereas plasma adiponectin levels were significantly lower, in patients who developed malignancy. Cox proportional hazards analysis revealed that insulin levels, homeostasis model assessment of insulin resistance, and lower adiponectin were independent predictors of malignancy. These findings demonstrate that insulin resistance and lower adiponectin levels could be risk factors for malignancy in nondiabetic PD patients. PMID- 20303126 TI - Dietary glycemic index, glycemic load, and intake of carbohydrate and rice in relation to risk of mortality from stroke and its subtypes in Japanese men and women. AB - We assessed the relationship of the dietary glycemic index (GI), glycemic load (GL), and intake of carbohydrate and rice, and risk of mortality from stroke and its subtypes. The cohort consisted of 12,561 men and 15,301 women residing in Takayama, Japan, in 1992. At the baseline, a food frequency questionnaire was administered; and the dietary GI, GL, and intake of carbohydrates and rice were estimated. Deaths from stroke occurring in the cohort were prospectively noted until 1999 with data from the office of the National Vital Statistics. The risk of mortality from stroke was assessed with a Cox proportional hazard model after adjusting for age; body mass index; smoking status; physical activity; history of hypertension; education; and intake of total energy, alcohol, dietary fiber, salt, and total fat. The risk of stroke subtypes was assessed in the age-adjusted model. The hazard ratios of total stroke comparing the highest vs the lowest quartiles of the dietary GI were 0.78 (95% confidence interval [CI], 0.41-1.47) with P(trend) = .50 in men and 2.09 (95% CI, 1.01-4.31) with P(trend) = .10 in women. Among women, the association was also significant with the risk of ischemic stroke (hazard ratio = 2.45; 95% CI, 1.01-5.92; P(trend) = .03); and a significant positive trend was also observed between dietary GL and mortality from hemorrhagic stroke (P(trend) = .05). The current study implies that diets with a high dietary GI increase the risk of mortality from stroke among Japanese women. PMID- 20303127 TI - Effect of niacin on prebeta-1 high-density lipoprotein levels in diabetes. AB - Prebeta-1 high-density lipoprotein (HDL) is an acceptor of peripheral free cholesterol and thus a participant in reverse cholesterol transport. Because patients with diabetes may have defects in reverse cholesterol transport, we hypothesized that (1) prebeta-1 HDL might be decreased in diabetes and (2) because niacin improves reverse cholesterol transport and may stimulate prebeta-1 HDL maturation, niacin would further decrease steady-state levels of prebeta-1 HDL in diabetes. Absolute levels of prebeta-1 HDL mass were measured using an isotopic dilution-ultrafiltration assay that measures apolipoprotein (apo) A-I after physically isolating prebeta-1. Plasma apo A-I concentration and routine lipids were also evaluated in 11 diabetic patients. Diabetic subjects have a nearly 50% reduction of circulating levels of prebeta-1 HDL to 36 +/- 22 (1 SD) MUg/mL compared with our previously published values of 73 +/- 44 MUg/mL in 136 healthy subjects. After niacin therapy, there was a further 17% reduction of prebeta-1 HDL levels to 30 +/- 26 MUg/mL (P < .026) compared with baseline. The percentage of prebeta-1 HDL in diabetic patients, as a percentage of total apo A I, was about half of the normal value of 6.1% +/- 3.6%; after niacin in diabetic patients, the percentage further decreased from 3.3% +/- 2.1% to 2.3% +/- 1.9% (P < .003). Absolute levels of apo A-I were similar in diabetic patients (1.14 +/- 0.29) and healthy subjects (1.24 +/- 0.24), and were unchanged by niacin in diabetic patients. We conclude with the novel observations that diabetes is associated with significantly reduced levels of prebeta-1 HDL and that, after niacin treatment, a further lowering of prebeta-1 HDL levels occur. Several altered mechanisms of RCT in diabetes are consistent with low levels of prebeta-1 HDL both before and after niacin treatment. PMID- 20303129 TI - Contribution of APOA5-1131C allele to the increased susceptibility of diabetes mellitus in association with higher triglyceride in Korean women. AB - Apolipoprotein A5 (APOA5) -1131C allele is associated with higher triglyceride, an independent cardiovascular risk factor and a commonly recognized lipid abnormality in diabetes mellitus (DM). We investigated the association of APOA5 1131T>C or S19W with DM. Study subjects were all women and categorized into metabolically healthy controls (n = 2033) and DM subjects (n = 304). Association of APOA5 -1131T>C with DM was calculated by odds ratio (OR). Anthropometric parameters, fasting glucose, and lipid profiles were measured. C carriers, particularly those with CC homozygote, had higher triglyceride and lower high density lipoprotein cholesterol in both healthy controls (P < .001 and P < .001) and DM patients (P = .002 and P = .006) after the adjustment for age, body mass index, menopause, smoking, and drinking. APOA5 -1131C allele was associated with an increased risk of DM (OR, 1.61 [95% confidence interval {CI}, 1.23-2.10]; P < .001) after adjustment for the above confounders. Further adjustment for fasting triglyceride or/and high-density lipoprotein cholesterol attenuated a little bit, but still significantly increased the risk of DM in C carriers (OR(2), 1.36 [95% CI, 1.02-1.80]; P = .035 and OR(3), 1.36 [95% CI, 1.032-1.79]; P = .029, respectively). Interestingly, C allele carriers in DM patients showed a positive correlation between fasting glucose and triglyceride after the adjustment (r = 0.172, P = .035). On the other hand, this significant correlation was not observed in healthy women. Regarding S19W, minor allele was not found in our study population from prescreening test. In conclusion, APOA5 -1131C allele may contribute to the increased susceptibility of DM in Korean women. In addition, positive correlation between fasting glucose and triglyceride in C carriers of DM patients suggested that C allele in hyperglycemic states may be more susceptible to the risk of cardiovascular disease. PMID- 20303130 TI - [Lacrimal gland epithelial tumors]. AB - Epithelial tumors of the lacrimal gland account for 50% of the expansive lesions of the lacrimal fossa. Pleomorphic adenomas have a good prognosis if surgery achieves en bloc removal distant from the tumoral capsule. Nevertheless, despite more severe treatment, the average survival remains limited for adenocarcinomas and cylindromas. PMID- 20303128 TI - Widespread effects of nicotinic acid on gene expression in insulin-sensitive tissues: implications for unwanted effects of nicotinic acid treatment. AB - Nicotinic acid (NA; or niacin) has been used as a hypolipidemic agent for more than 4 decades. However, the mechanisms underlying the effects of NA treatment (wanted and unwanted) are still poorly understood. In the present study, we discovered that NA infusion in rats resulted in dephosphorylation (ie, activation) of the forkhead transcription factor FOXO1 in insulin-sensitive tissues such as skeletal and cardiac muscles, liver, and adipose tissue. These NA effects were opposite to the effects of insulin to increase FOXO1 phosphorylation. To test whether NA alters gene expression in these tissues, rats were infused for 7 hours with NA (30 MUmol/h) and/or insulin (5 mU/[kg min]); and gene expression was evaluated using a microarray analysis. Nicotinic acid had widespread effects on gene expression in all of the tissues studied, and the number of genes affected by NA greatly exceeded that of genes affected by insulin. A systematic (or strategic) analysis of the microarray data revealed that there were numerous genes whose expression was regulated inversely by insulin and NA in correlation with FOXO1 phosphorylation, representing potential FOXO1 target genes. We also identified a group of genes whose expression was altered by NA exclusively in adipose tissue, presumably because of stimulation of the NA receptor in this tissue. Finally, there were genes whose expression was altered by both NA and insulin, likely via lowering plasma free fatty acid levels, including lipoprotein lipase and adenosine triphosphate-binding cassette A1, which play a major role in the regulation of circulating lipids. Thus, our data suggest that NA alters gene expression in insulin-sensitive tissues by various mechanisms. Some of the NA-induced changes in gene expression are discussed as potential mechanisms underlying wanted and unwanted effects of NA treatment. PMID- 20303131 TI - [Orbitotemporal facial involvement in type 1 neurofibromatosis (NF1)]. AB - Plexiform neurofibromas of the orbit, sometimes extending to the temporal region and the face, are considered to be a rare but devastating and disfiguring complication of neurofibromatosis type 1. The first symptoms appear in infancy and the involvement of the orbit and the face is present in nearly all children after the age of 5. The disease is unilateral in most cases but can exceptionally involve both sides of the face. Progressive deformation of the orbital frame due to the expanding plexiform neurofibroma and buphthalmos occurs in a large proportion of cases. The associated sphenoidal dysplasia, which is thought to be, according to the most recent hypothesis, genetically determined, will inescapably increase the burden to the orbital content, cause pulsating proptosis and will endanger noble structures, finally resulting in loss of vision. Using the Jackson classification, the authors report their personal series of 22 cases (19 operated). Until now, there has been no effective medical treatment for plexiform neurofibroma and surgery remains the standard care for these patients. Controversies remain about the timing of the first operation and today most multidisciplinary teams involving plastic, maxillofacial, ophthalmologic, and neurosurgeons favor early intervention to try to minimize the secondary deformation of the orbital and facial skeleton. A number of cases of plexiform neurofibromas are illustrated within the three Jackson groups and treatment results of the rare elephantiasis neuromatosa cases are presented. Special techniques such as preoperative embolization of heavily vascularized plexiform neurofibroma are also discussed. PMID- 20303132 TI - Analysis of 1-deoxy-D-xylulose 5-phosphate synthase activity in Grey poplar leaves using isotope ratio mass spectrometry. AB - Deoxy-xylulose phosphate synthase (DXS) catalyzes the first step of the methylerythritol phosphate (MEP) pathway and it might regulate the metabolic flux in plastidic isoprenoid biosynthesis. We developed a sensitive assay suitable for plant extracts that is based on the decarboxylation of labeled pyruvate (1-(13)C) PYR and detection of (13)CO(2) by isotope ratio mass spectrometry. We tested our method investigating the DXS activity in poplar leaves. Apparent DXS activity showed Michaelis constants of 111 and 158 microM for glyceraldehyde phosphate and pyruvate, respectively; pH and temperature optima were found at pH 8.6 and 45 degrees C. DXS activity was inhibited when the competitive inhibitor beta fluoropyruvate was added to the reaction mixture. DXS activity strongly depended on leaf development with higher activity in young leaves and correlated fairly well with leaf isoprene emission potential. In mature poplar leaves, isoprene emission is the main metabolic sink of plastidic isoprenoid intermediates. Consequently, we found lower DXS activity in non-isoprene-emitting lines of poplar than in emitting plants as indicator of a lower demand of metabolic flux within the MEP pathway. PMID- 20303133 TI - Identification of JAK-STAT pathways as important for the anti-inflammatory activity of a Hypericum perforatum fraction and bioactive constituents in RAW 264.7 mouse macrophages. AB - Hypericum perforatum extracts have been used to treat diseases, including mild-to moderate depression and inflammatory conditions. It is particularly important to identify which constituents present in the H. perforatum extracts are responsible for its anti-inflammatory activity since consumers are taking H. perforatum preparations to treat inflammation. We used a combination of four putative bioactive constituents, called the 4-component-system that interacted synergistically to explain the light-activated anti-inflammatory activity of an H. perforatum fraction in RAW 264.7 mouse macrophages. We also combined the constituents at concentrations detected in the fraction to identify key molecular targets. LPS was used to model an inflammatory response, and the 4-component system and H. perforatum fraction were used as treatments that inhibited LPS induced prostaglandin E(2) (PGE(2)) production in RAW 264.7 mouse macrophages in the studies of gene expression profiles. We used Affymetrix genechips, statistical analysis, and quantitative real-time PCR to identify key gene targets of the 4-component-system and the sub-fraction from an H. perforatum ethanol extract. The H. perforatum sub-fraction, with or without LPS stimulation, affected far more genes than the 4-component-system with and without LPS. Genes involved in Janus kinase, as well as a signal transducer and activator of transcription (JAK-STAT) and eicosanoid pathways were identified that could account for the reduction in PGE(2) observed with both treatments in LPS stimulated macrophages. Ten genes may be particularly important targets for activity of the 4-component-system and the fraction with LPS stimulation and these genes were involved in inflammatory signaling pathways, namely the JAK-STAT and eicosanoid pathways. PMID- 20303134 TI - Factors affecting the occurrence, duration of hospitalization and final outcome in canine parvovirus infection. AB - The objectives of this matched case-control study in a veterinary teaching hospital were to investigate the influence of signalment and historical data on the odds of occurrence of canine parvovirus (CPV) enteritis and the potential usefulness of the clinical signs and clinicopathologic abnormalities recorded on admission as prognostic indicators of mean duration of hospitalization (DOH) and outcome of the disease. Ninety-four puppies with natural CPV enteritis and 188 age-matched controls were studied. The odds to develop CPV enteritis were higher in purebreds compared to mixed-breed puppies. Vomiting and depression at the time of admission were associated with a prolongation of DOH by 2 and 1.75 days, respectively. The lymphopenic and hypoalbuminemic dogs were hospitalized for 1.9 and 2.5 more days, respectively, compared to those without these abnormalities. The odds of non-survival were higher in those puppies with evidence of systemic inflammatory response syndrome (SIRS) at the time of admission. PMID- 20303136 TI - Simultaneous nitrification, denitrification and carbon removal in microbial fuel cells. AB - Microbial fuel cells (MFCs) can use nitrate as a cathodic electron acceptor, allowing for simultaneous removal of carbon (at the anode) and nitrogen (at the cathode). In this study, we supplemented the cathodic process with in situ nitrification through specific aeration, and thus obtained simultaneous nitrification and denitrification (SND) in the one half-cell. Synthetic wastewater containing acetate and ammonium was supplied to the anode; the effluent was subsequently directed to the cathode. The influence of oxygen levels and carbon/nitrogen concentrations and ratios on the system performances was investigated. Denitrification occurred simultaneously with nitrification at the cathode, producing an effluent with levels of nitrate and ammonium as low as 1.0+/-0.5 mg N L(-1) and 2.13+/-0.05 mg N L(-1), respectively, resulting in a nitrogen removal efficiency of 94.1+/-0.9%. The integration of the nitrification process into the cathode solves the drawback of ammonium losses due to diffusion between compartments in the MFC, as previously reported in a system operating with external nitrification stage. This work represents the first successful attempt to combine SND and organics oxidation while producing electricity in an MFC. PMID- 20303135 TI - Lambda and alpha interferons inhibit hepatitis B virus replication through a common molecular mechanism but with different in vivo activities. AB - The type III interferons (IFN-lambda1, 2, and 3) induce an antiviral response similar to IFN-alpha/beta, but mediate their activity through a unique receptor. We found that like IFN-alpha/beta, IFN-lambda prevents the assembly of HBV capsids, demonstrating convergence of the two signaling pathways through a single antiviral mechanism. In contrast to IFN-lambda, the structurally related cytokine interleukin (IL)-22 only minimally reduced HBV replication. The transcriptional program activated by IL-22 displayed little similarity to that induced by IFN lambda, but instead resembled the response elicited by IL-6. We also found that murine IFN-lambda2 had only weak antiviral activity against HBV in the liver of transgenic mice, and that human IFN-lambda2 activity in serum correlated with the sensitivity of the cytokine to proteases. These results demonstrate that the IFN alpha/beta and IFN-lambda anti-HBV responses operate through a single molecular mechanism, and support the notion that IFN-lambda plays a local, rather than systemic, role in antiviral immunity. PMID- 20303137 TI - Electrical field: a historical review of its application and contributions in wastewater sludge dewatering. AB - Electric field-assisted dewatering, also called electro-dewatering, is a technology in which a conventional dewatering mechanism such a pressure dewatering is combined with electrokinetic effects to realize an improved liquid/solids separation, to increase the final dry solids content and to accelerate the dewatering process with low energy consumption compared to thermal drying. Electro-dewatering is not a new idea, but the practical industrial applications have been limited to niche areas in soil mechanics, civil engineering, and the ceramics industry. Recently, it has received great attention, specially, in the fields of fine-particle sludge, gelatinous sludge, sewage sludge, pharmaceutical industries, food waste and bull kelp, which could not be successfully dewatered with conventional mechanical methods. This review focuses on the scientific and practical aspects of the application of an electrical field in laboratory/industrial dewatering, and discusses this in relation to conventional dewatering techniques. A comprehensive bibliography of research in the electro-dewatering of wastewater sludges is included. As the fine particle suspensions possess a surface charge, usually negative, they are surrounded by a layer with a higher density of positive charges, the electric double layer. When an electric field is applied, the usually negative charged particles move towards the electrode of the opposite charge. The water, commonly with cations, is driven towards the negative electrode. Electro-dewatering thus involves the well-known phenomena of electrophoresis, electro-osmosis, and electromigration. Following a detailed outline of the role of the electric double layer and electrokinetic phenomena, an analysis of the components of applied voltage and their significance is presented from an electrochemical viewpoint. The aim of this elementary analysis is to provide a fundamental understanding of the different process variables and configurations in order to identify potential improvements. Also discussed herein is the investigation of the electrical behaviour of a porous medium, with particular emphasis on porous medium conductivity determination. PMID- 20303138 TI - Removal of sulfadiazine, sulfamethizole, sulfamethoxazole, and sulfathiazole from aqueous solution by ozonation. AB - The removal of sulfadiazine, sulfamethizole, sulfamethoxazole, and sulfathiazole from aqueous solution by ozonation was studied. The study was conducted experimentally in a semi-batch reactor under different experimental conditions, i.e., varying influent ozone gas concentration, bicarbonate ion concentration, and pH. The results of the study indicated that ozonation could be used to effectively remove the sulfonamides from water. The sulfonamides exhibited moderate reactivity towards aqueous ozone, k(O)(3) >2 x 10(4) M(-1)s(-1) at pH of 2 and 22 degrees C. The mol of ozone absorbed by the solution per mol of sulfonamides removed varied in the range of 5.5-12.0 with lower ranges representing ozone absorption by the solution at the beginning of the ozonation process whereas higher ratios correspond to >99.9% removal of the target sulfonamides. The removal rate of the sulfonamides improved with bicarbonate ion concentration up to 8mM but further increase in bicarbonate ion decreased removal efficiency. It was also observed that increasing the pH from 2.0 to 10.0 resulted in enhanced removal of the sulfonamides. PMID- 20303139 TI - Detection of Dechlorane Plus in fish from urban-industrial rivers. AB - A highly chlorinated flame retardant, Dechlorane Plus (DP), was measured in five fish species collected in 2008 from 22 river sites across South Korea. The sites consisted of 15 urban-industrial areas, three rural-industrial areas, and four rural rivers. Both syn- and anti-DP isomer were consistently detected in all fish samples regardless of sampling sites and fish species. DP has become a widespread environmental pollutant in South Korea. Concentrations of summation operatorDP isomers ranged from 0.61 to 126ngg(-1) lipid, with a mean concentration of 24.5ngg(-1) lipid. The mean summation operatorDP concentrations in the 15 urban sites (36.1+/-35.3ngg(-1) lipid) were approximately 25 times greater than those measured in the rural sites (1.4+/-1.0ngg(-1) lipid). The summation operatorDP concentrations in this study exceeded those determined in fish from the Great Lakes. DP exposure to fish is related to urbanization activity. Specific urban areas could be significant source areas of DP exposure, even in the absence of a local DP manufacturing facility. Concentrations of syn- and anti-DP isomer ranged from 0.17 to 30ngg(-1) lipid and 0.44 to 97ngg(-1) lipid, respectively. The anti DP isomer was dominant in all samples. However, the mean f(anti) value for urban industrial samples (0.67+/-0.060) was significantly lower than that of the technical DP standard (f(anti)=0.75; p=0.032). This observation supports that DP isomers exhibit different bioaccumulation behaviors and that syn-DP isomer more easily accumulates in biota samples than anti-DP isomer does. PMID- 20303140 TI - Epidermal growth factor receptor in glioblastomas: correlation between gene copy number and protein expression. AB - Epidermal growth factor receptor is a transmembrane receptor involved in oncogenesis, including the development of glioblastoma. We studied the prognostic significance of epidermal growth factor receptor amplification as determined by fluorescence in situ hybridization, quantitative polymerase chain reaction, and protein expression by immunohistochemistry. Ninety-nine patients exhibiting glioblastoma were included. Immunohistochemistry was performed on microarray blocks with clone 25, which recognizes both epidermal growth factor receptor wild type and vIII, and scored using a semiquantitative approach. Quantitative polymerase chain reaction and fluorescence in situ hybridization techniques were performed on frozen section: 29.3% of cases had a high epidermal growth factor receptor immunohistochemistry score (score >/=200); and of these cases, 96.5% had gene amplification by fluorescence in situ hybridization and quantitative polymerase chain reaction. Conversely, of cases with a low immunohistochemistry score, 72.9% had normal karyotype or polysomy 7 by fluorescence in situ hybridization technique; but around 25% had gene amplification by fluorescence in situ hybridization and quantitative polymerase chain reaction. In the case of protein overexpression, quantitative polymerase chain reaction and fluorescence in situ hybridization could be avoided in first intention because their positive predictive value for amplification is 97%. In multivariate analysis, there was a trend toward an association between shorter overall survival time and epidermal growth factor receptor amplification as determined by fluorescence in situ hybridization analysis. However, cases with an immunohistochemistry score less 200 require further testing by fluorescence in situ hybridization or quantitative polymerase chain reaction. PMID- 20303141 TI - Mitogenic cardiomyopathy: a lethal neonatal familial dilated cardiomyopathy characterized by myocyte hyperplasia and proliferation. AB - Pediatric cardiomyopathies are a heterogenous group of conditions of which dilated cardiomyopathies are the most common clinicomorphologic subtype. However, the etiology and pathogenesis of many cases of dilated cardiomyopathies remain unknown. We describe a series of 5 cases of a rare but clinically and histologically distinctive dilated cardiomyopathy that was uniformly lethal in early infancy. The 5 cases include 2 pairs of siblings. There was parental consanguinity in 1 of the 2 pairs of siblings. Death occurred in early infancy (range, 22-67 days; mean, 42 days) after a short history of general lethargy, decreased feeding, respiratory distress, or cyanosis. There was no specific birth or early neonatal problems. Autopsy revealed congestive cardiac failure and enlarged, dilated hearts with ventricular dilatation more pronounced than atrial dilatation, and endocardial fibroelastosis. Histology showed prominent hypertrophic nuclear changes of cardiac myofibers and markedly increased myocyte mitotic activity including occasional atypical mitoses. Immunohistochemical staining for Mib1 showed a markedly increased proliferative index of 10% to 20%. Ancillary investigations, including molecular studies, did not reveal a primary cause for the cardiomyopathies. This distinctive dilated cardiomyopathy characterized by unusual histologic features of myocyte nuclear hypertrophy and marked mitotic activity is lethal in early infancy. Its occurrence in 2 pairs of siblings suggests familial inheritance. Although the underlying molecular pathogenesis remains to be elucidated, it is important to recognize this distinctive entity for purposes of genetic counseling. PMID- 20303142 TI - Morphometrics and phylogenetics: principal components of shape from cranial modules are neither appropriate nor effective cladistic characters. PMID- 20303143 TI - Cultural conservatism and variability in the Acheulian sequence of Gesher Benot Ya'aqov. AB - The Acheulian Technocomplex exhibits two phenomena: variability and conservatism. Variability is expressed in the composition and frequencies of tool types, particularly in the varying frequencies of bifaces (handaxes and cleavers). Conservatism is expressed in the continuous presence of bifaces along an immense time trajectory. The site of Gesher Benot Ya'aqov (GBY) offers a unique opportunity to study aspects of variability and conservatism as a result of its long cultural-stratigraphic sequence containing superimposed lithic assemblages. This study explores aspects of variability and conservatism within the Acheulian lithic assemblages of GBY, with emphasis placed on the bifacial tools. While variability has been studied through a comparison of typological frequencies in a series of assemblages from the site, evidence for conservatism was examined in the production modes expressed by the reduction sequence of the bifaces. We demonstrate that while pronounced typological variability is observed among the GBY assemblages, they were all manufactured by the same technology. The technology, size, and morphology of the bifaces throughout the entire stratigraphic sequence of GBY reflect the strong conservatism of their makers. We conclude that the biface frequency cannot be considered as a chrono/cultural marker that might otherwise allow us to distinguish between different phases within the Acheulian. The variability observed within the assemblages is explained as a result of different activities, tasks, and functions, which were carried out at specific localities along the shores of the paleo-Hula Lake in the early Middle Pleistocene. PMID- 20303144 TI - Lower Paleolithic hominin ecology at the fringe of the desert: Faunal remains from Bizat Ruhama and Nahal Hesi, Northern Negev, Israel. AB - The Southern Levant is a pivotal area for the study of hominin paleoecology during the Lower Paleolithic, because of its location on the out-of-Africa dispersal route and its significant ecological diversity. Important information has been gained by archaeofaunal studies, which usually reveal that exploitation of diverse Mediterranean environments with woodlands, marshes and lake margins, represents a dominant subsistence strategy for Lower Paleolithic hominins. Here, we present new taxonomic and taphonomic data from two sites in the southern coastal plain of the Southern Levant, at the fringe of the Negev Desert: Bizat Ruhama (Early Pleistocene) and Nahal Hesi (Middle Pleistocene). The sites preserve anthropogenic faunas, with the former signaling a marrow-exploitation strategy, perhaps related to scavenging from carnivore kills, and the latter showing evidence for primary access to fleshed ungulate carcasses. The species composition of these Northern Negev sites is unique for the Levantine Lower Paleolithic in that these sites lack typical woodland and riparian species, probably indicating an open, relatively uniform environment with patchy water sources and trees, much like this semiarid region today. Bizat Ruhama and Nahal Hesi are among the only Levantine Lower Paleolithic faunas associated with such a setting, thereby widening the known spectrum of environments exploited by hominins in the region. It is suggested that the two sites, coupled with the nearby Late Pleistocene evidence, reflect a largely stable semiarid environment on the northwestern fringe of the Negev Desert throughout much of the Pleistocene. PMID- 20303145 TI - Bioaccumulation of silver in ectomycorrhizal and saprobic macrofungi from pristine and polluted areas. AB - Macrofungi are effective accumulators of Ag. This study provides a comprehensive review of this phenomenon supported by original data on the Ag concentrations of macrofungi from pristine and Ag-polluted areas. In pristine areas, the median Ag concentrations of ectomycorrhizal (ECM) and saprobic (SAP) macrofungi were 0.79 and 2.94 mg kg(-1), respectively. In these areas, hyperaccumulation thresholds for Ag in ECM and SAP macrofungi are proposed as 100 and 300 mg kg(-1), respectively. In a Ag-polluted area, the Ag concentrations in macrofungi (ECM and SAP) were significantly elevated with the median value of 24.7 mg kg(-1) and the highest concentrations in Amanita spp. of the section Vaginatae (304-692 mg kg( 1)). The intracellular speciation of Ag in fruit-bodies of the Ag-accumulator Amanita submembranacea was inspected by size exclusion chromatography followed by sulfhydryl-specific fluorimetric assays of ligands using reverse phase high performance liquid chromatography and improved polyacrylamide gel electrophoresis. Virtually all Ag was found to be intracellular and sequestered in the major 7 kDa and minor 3.3 kDa complexes. The lack of glutathione and phytochelatins and the presence of a single 3 kDa sulfhydryl-containing peptide in the isolated Ag-complexes suggest that detoxification of Ag in A. submembranacea may rely on metallothionein. Vertical distribution of Ag in a polluted forest soil profile has shown substantial enrichment in organic horizons; in polluted technosol, the highest Ag concentrations were found in surface layers. Standardized EDTA extraction of Ag in both the investigated soil profiles showed relatively low Ag extractibility, generally within the range of 2.2-7.7% of total Ag content. PMID- 20303146 TI - Presence and fate of priority substances in domestic greywater treatment and reuse systems. AB - A wide range of household sources may potentially contribute to contaminant loads in domestic greywater. The ability of greywater treatment systems to act as emission control barriers for household micropollutants, thereby providing environmental benefits in addition to potable water savings, have not been fully explored. This paper investigates the sources, presence and potential fate of a selection of xenobiotic micropollutants in on-site greywater treatment systems. All of the investigated compounds are listed under the European Water Framework Directive as either "Priority Substances" (PS) or "Priority Hazardous Substances" (PHS). Significant knowledge gaps are identified. A wide range of potential treatment trains are available for greywater treatment and reuse but treatment efficiency data for priority substances and other micropollutants is very limited. Geochemical modelling indicates that PS/PHS removal during treatment is likely to be predominantly due to sludge/solid phase adsorption, with only minor contributions to the water phase. Many PS/PHS are resistant to biodegradation and as the majority of automated greywater treatment plants periodically discharge sludge to the municipal sewerage system, greywater treatment is unlikely to act as a comprehensive PS/PHS emission barrier. Hence, it is important to ensure that other source control options (e.g. eco-labeling, substance substitution, and regulatory controls) for household items continue to be pursued, in order that PS/PHS emissions from these sources are effectively reduced and/or phased out as required under the demands of the European Water Framework Directive. PMID- 20303147 TI - Radical retropubic prostatectomy and robotic-assisted laparoscopic prostatectomy: likelihood of positive surgical margin(s). AB - OBJECTIVES: To evaluate whether the surgical approach influenced the likelihood of a positive surgical margin (PSM) adjusting for known preoperative predictors of PSM, year of radical prostatectomy, body mass index, use of nerve sparing, and patient age at radical prostatectomy. METHODS: The study cohort comprised 950 consecutively treated men with clinically localized prostate cancer who underwent open radical retropubic (RRP, n = 346) or robotic-assisted (RALP, N = 604) prostatectomy by a single surgeon (J.P.R., J.C.H.) at the Brigham and Women's Hospital from 2005 to 2008 and had complete information on baseline patient and tumor characteristics. Univariate and multivariate logistic regression analyses were performed to identify clinical factors significantly associated with the likelihood of a PSM. RESULTS: Men undergoing RALP compared with RRP were more likely to have a PSM (adjusted odds ratio 1.9; 95% confidence interval: 1.2-3.1, P = .0095). Significant interaction (P = .0085) was noted between the type of surgical approach and whether nerve sparing was performed on the likelihood of a PSM. Specifically, a significantly lower PSM rate was observed for men undergoing nerve sparing and RRP compared with nerve sparing and RALP (7.6% vs 13.5%, P = .007), whereas opposite trend was noted (P = .09) for men undergoing a non-nerve sparing approach. CONCLUSIONS: Men undergoing RALP compared with RRP seem to have a greater likelihood of a PSM. Further study is needed to delineate whether this increase is due to an intrinsic limitation of RALP or unknown confounders. PMID- 20303148 TI - Benign lesions after partial nephrectomy for presumed renal cell carcinoma in masses 4 cm or less: prevalence and predictors in Korean patients. AB - OBJECTIVES: To investigate the prevalence and predictors associated with benign lesions in Korean patients after partial nephrectomy for presumed renal cell carcinoma (RCC) for lesions measuring <= 4 cm. METHODS: We retrospectively investigated the medical records of 376 patients who underwent partial nephrectomy for presumed RCC with renal masses of size <= 4 cm between June 1997 and December 2008. Demographic and clinicopathologic parameters were compared between benign lesions and RCC. Logistic regression was done to identify parameters associated with benign lesions. RESULTS: In the 376 patients, 81 tumors (21.5%) were benign, including 35 angiomyolipomas (9.3%), 26 complicated cysts (6.9%), 11 oncocytomas (2.9%), and 9 others (2.4%). Univariate analysis showed that time of surgery, female sex, younger age, and normal body mass index (body mass index (BMI) < 23 kg/m(2)) were associated with benign pathologic findings. On multiple logistic regression analysis, female sex (OR, 4.91; 95% CI, 2.76-08.75; P < .001), age (OR, 0.97; 95% CI, 0.95-0.99; P = .009), and time of surgery (OR, 0.33; 95% CI, 0.11-0.95; P = .040) were independent predictors of benign histologic features. Tumor size, incidental diagnosis, and BMI were not significant predictors (P > .05). CONCLUSIONS: Our study with a large cohort of Asian patients showed that the prevalence of benign lesions was similar to previously reported Western studies. However, the most common benign lesion was angiomyolipoma, compared with oncocytoma in Western countries. The results of this study may help clinicians counsel female and younger patients recently diagnosed with small renal masses and decide the most appropriate treatment, including renal biopsies and close observation. PMID- 20303149 TI - Single-site laparoscopic orchidopexy in an infant. AB - We describe a laparoscopic orchidopexy performed on an 18-month-old child through a single infraumbilical site. PMID- 20303150 TI - A review: the application of minimally invasive surgery to pediatric urology: lower urinary tract reconstructive procedures. AB - This paper is one-half of a 2 part review on minimally-invasive procedures in pediatric urology. This article focuses on lower tract procedures, including ureteroureterostomy, anti-reflux surgeries, creation of continent catheterizable channels, and augmentation cystoplasty. We note important articles on pure laparoscopic as well as robotic-assisted laparoscopic lower urinary tract surgeries, concentrating on their techniques and outcomes. PMID- 20303151 TI - A review: the application of minimally invasive surgery to pediatric urology: upper urinary tract procedures. AB - This paper is one-half of a 2 part review on minimally-invasive procedures in pediatric urology. This article focuses on upper tract procedures, including complete nephrectomy, partial nephrectomy, pyeloplasty, and ureterocalicostomy. We note important articles on pure laparoscopic as well as robotic-assisted laparoscopic upper urinary tract surgeries, concentrating on their techniques and outcomes. PMID- 20303152 TI - Detection rates of nonpalpable prostate cancer in Korean men with prostate specific antigen levels between 2.5 and 4.0 ng/mL. AB - OBJECTIVE: To evaluate the detection rate and pathology of cancer in Korean men with low levels of prostate-specific antigen (PSA), 2.5-4.0 ng/mL. METHODS: We examined 1097 patients with PSA level of 2.5-10.0 ng/mL, who underwent transrectal ultrasonography-guided prostate needle biopsies between January 2008 and March 2009. Of the 1097 biopsy patients, 815 met our criteria of benign findings by digital rectal examination and the absence of cancerous lesions by TRUS. Clinical characteristics and detection rates of prostate cancer, as well as the pathology of specimens obtained by needle biopsies and prostatectomies, were evaluated in these patients. RESULTS: Of the 815 patients, 349 had group 1 (PSA level, 2.5-4.0 ng/mL) and 466 had group 2 (PSA level, 4.0-10.0 ng/mL). The percentage of patients diagnosed with prostate cancer was not statistically different between the 2 groups (21.8% in group 1, and 20.2% in group 2). In group 1, 70.7% of patients had a pathologic Gleason score of 7 or higher and 91.4% had organ-confined tumors (pT2). The pathologic characteristics, including Gleason score, pathologic stage, and percentage of insignificant cancer were similar in prostatectomy specimens between group 1 and group 2. CONCLUSIONS: Detection rates of nonpalpable prostate cancer in Korean men were 21.8% in group 1 and 20.2% in group 2 without statistically significant difference. Pathologic characteristics of prostatectomy specimens also were similar between group 1 and group 2. These results suggest that a lower PSA level might be considered as an indication for prostate biopsy. PMID- 20303153 TI - How do young residents practice laparoscopic surgical skills? AB - OBJECTIVES: To investigate whether a training system using a dry box is feasible for training young urologists. Despite laparoscopic surgery being widely indicated for several urological diseases, a laparoscopic training system for young urologists has not been fully established yet. However, the learning curve for laparoscopic surgery has not yet been ascertained. METHODS: We continued to test 11 sixth-year residents (postgraduate year: PGY6) and third-year residents (PGY3) in our department in terms of surgical skills using a dry box. We gave them several tasks (cutting and suturing) and let them practice until task completion. We continued to test all participants by these tasks for 16 weeks. RESULTS: At the beginning of the present study, the PGY6 residents achieved significantly better scores than the PGY3 residents. However, the difference between the 2 groups became insignificant over time. Furthermore, statistical analysis revealed that a practice time of 100 minutes per week was the only significant factor affecting the last test score. For the final test, the mean practice time for all participants was 79.1 minutes per week. CONCLUSIONS: These results suggest that laparoscopic surgical skills can definitely be polished by adequate voluntary practice. PMID- 20303154 TI - Extracellular matrix degradation and reduced neural density in children with intrinsic ureteropelvic junction obstruction. AB - OBJECTIVES: To investigate the extracellular matrix microenvironment and nerve supply of ureteropelvic junctions (UPJs) in children with intrinsic UPJ obstruction. Congenital UPJ obstruction is the most common cause of neonatal hydronephrosis. Although many studies investigating the molecular changes within this segment have been performed, the underlying mechanisms of UPJ obstruction are still unclear. METHODS: Specimens were obtained from 21 children with a mean age of 103.2 months undergoing dismembered pyeloplasty. Control samples included 9 archival specimens from age-matched children without any history of urologic disease. Paraffin-embedded sections were immunostained to detect matrix metalloproteinase 2 (MMP-2), tenascin C (TN-C), and S-100 (for the neuronal supply). Expression patterns were investigated using semiquantitative high-power field magnification analyses, and the MMP-2 and TN-C immunoreactivity were scored. Differences between the 2 groups were examined statistically. RESULTS: All UPJ specimens displayed a resolved muscular coat and replacement of smooth muscle cells by connective tissue. The degree of MMP-2 expression representing matrix turnover was statistically significantly elevated. Similarly, TN-C expression was found to be higher in obstructed specimens. Additionally, the mean S-100 staining was lower than in controls. Although S-100-positive nerve-fibers were more predominant in the adventitia with minimal submucosal and absent intramuscular staining in patient specimens, they were abundant in both adventitia and submucosa with minimal intramuscular staining in the controls. CONCLUSIONS: In intrinsic UPJ obstruction samples, a dissolved smooth muscular coat and an overexpression of extracellular matrix proteins, together with depleted nerve supply, was demonstrable. PMID- 20303155 TI - Salvage therapy with bicalutamide 150 mg in nonmetastatic castration-resistant prostate cancer. AB - OBJECTIVES: To evaluate the rate and duration of prostate-specific antigen (PSA) response to high-dose bicalutamide (150 mg) in nonmetastatic castration-resistant prostate cancer patients and its impact on metastasis-free survival. METHODS: This single center, prospective study included 38 prostate cancer patients surgically or medically castrated who had PSA increases above their nadir after previous antiandrogen manipulation and in absence of bone metastases. Patients were given daily dose of bicalutamide 150 mg. Clinical evaluations and serum PSA testing were performed every 3 months. Response was defined according to PSA decline from baseline as if >= 50% or >= 85%. The duration of response was the time from entering into study until PSA increased >= 25% or >= 2 ng/ml from the nadir. Bone scintigraphy was repeated at PSA increase or at symptom appearance. RESULTS: The mean follow-up was 34.5 months (range, 3-75.2). A PSA decline was observed in 17 of 38 patients (44.7%): 7 (18.4%) >= 85% and 10 (26.3%) >= 50 but < 85% responders. The median duration of response was 18.5 months for partial and 37.4 months for complete responders. The median time to metastasis was 52.5 months for responders and 15.7 months for nonresponders (Log-Rank test 9.3, P = .002). CONCLUSIONS: High-dose bicalutamide can induce a second response in almost half of castration-resistant prostate cancer patients without metastasis. The duration of response is more than 1.5 years on average and responders have prolonged metastasis-free survival. PMID- 20303156 TI - Overcoming the barriers to HPV vaccination in high-risk populations in the US. AB - OBJECTIVES: To review populations of women in the United States at high risk for cervical cancer, assess known reasons for existing outcome disparities, and discuss potential strategies to reduce barriers to HPV vaccination and current strategies for cervical cancer prevention. METHODS: An expert forum conducted September 12-13, 2008, by the Society of Gynecologic Oncologists including 56 experts in cervical cancer and titled "Future strategies of cervical cancer prevention: what do we need to do now to prepare?" RESULTS: Although epidemiological data is useful and necessary to identify populations at high risk for cervical cancer, an understanding of the knowledge and attitudes regarding HPV and cervical cancer prevention of racial/ethnic groups and sub-groups within racial/ethnic categories is critical for the implementation of effective targeted and effective educational efforts. Inequities in cervical cancer screening, diagnosis and treatment and HPV vaccination may arise from a number of barriers including access to healthcare, cultural beliefs, and limited awareness of options. CONCLUSIONS: Initiatives to promote uptake of prophylactic HPV vaccination that target high-risk women need to be implemented before existing disparities widen. Although acceptability of HPV vaccination is promising, uptake is still low among low-income populations and specific racial/ethnic minorities. To address limited vaccine uptake it may be beneficial to establish national/state guidelines as well as culturally relevant interventions at the individual and community levels. The successful implementation of multiple integrated initiatives on HPV awareness, knowledge, and vaccination will diminish existing disparities in cervical cancer incidence and mortality. PMID- 20303158 TI - Second messenger-mediated adjustment of bacterial swimming velocity. AB - Bacteria swim by means of rotating flagella that are powered by ion influx through membrane-spanning motor complexes. Escherichia coli and related species harness a chemosensory and signal transduction machinery that governs the direction of flagellar rotation and allows them to navigate in chemical gradients. Here, we show that Escherichia coli can also fine-tune its swimming speed with the help of a molecular brake (YcgR) that, upon binding of the nucleotide second messenger cyclic di-GMP, interacts with the motor protein MotA to curb flagellar motor output. Swimming velocity is controlled by the synergistic action of at least five signaling proteins that adjust the cellular concentration of cyclic di-GMP. Activation of this network and the resulting deceleration coincide with nutrient depletion and might represent an adaptation to starvation. These experiments demonstrate that bacteria can modulate flagellar motor output and thus swimming velocity in response to environmental cues. PMID- 20303157 TI - Molecular and cellular approaches for diversifying and extending optogenetics. AB - Optogenetic technologies employ light to control biological processes within targeted cells in vivo with high temporal precision. Here, we show that application of molecular trafficking principles can expand the optogenetic repertoire along several long-sought dimensions. Subcellular and transcellular trafficking strategies now permit (1) optical regulation at the far-red/infrared border and extension of optogenetic control across the entire visible spectrum, (2) increased potency of optical inhibition without increased light power requirement (nanoampere-scale chloride-mediated photocurrents that maintain the light sensitivity and reversible, step-like kinetic stability of earlier tools), and (3) generalizable strategies for targeting cells based not only on genetic identity, but also on morphology and tissue topology, to allow versatile targeting when promoters are not known or in genetically intractable organisms. Together, these results illustrate use of cell-biological principles to enable expansion of the versatile fast optogenetic technologies suitable for intact systems biology and behavior. PMID- 20303159 TI - Interactive effect of indenter size and specimen thickness in Hertzian indentation test. AB - OBJECTIVE: To investigate the effect of indenter size on the failure mode of amalgam and its interaction with thickness. METHODS: Dental silver amalgam (Lojic+, SDI) discs, 10 mm diameter, thickness h=0.4-8.0 mm, were stored in air at 37 degrees C for 7 days before testing in 'Hertzian contact', resting freely on a 30% glass fibre-reinforced nylon 6,6 substrate (E: 10GPa) at 23 degrees C in air at a crosshead speed of 0.2 mm/min. The load at the first crack, detected acoustically, was recorded. Two series of tests were conducted. In the first, a 3 or 20 mm diameter hard steel ball was used to apply the load to discs with h=0.4 8.0 mm. The second was performed on discs with h=2.0 and 5.0 mm with indenter diameters D=2-40 mm. RESULTS: The failure loads for these two groups were substantially different, with most values for D=3 mm being lower than those for D=20 mm. The transitions of the main failure mode with increasing thickness were similar, i.e., from RC-dominant for h small to CC-dominant for h large, except that this occurred over a greater range for the larger indenter. For h=2 mm, failure load was constant for D=2-40 mm; all specimens consistently failed from bottom RC. For h=5 mm, failure load increased with D with a quadratic relationship up to about 10 mm (r(2)=0.85), after that, values were near constant; the failure mode gradually changed with D from PD- or CC-prevailing for D small (< or =5 mm) to RC-prevailing for D very large (30 and 40 mm). SIGNIFICANCE: The failure mode of amalgam is dependent on the indenter size; indenter size and coating thickness have reciprocal effects. PMID- 20303160 TI - Mechanical strength and subcritical crack growth under wet cyclic loading of glass-infiltrated dental ceramics. AB - OBJECTIVES: Evaluate the flexural strength (sigma) and subcritical crack growth (SCG) under cyclic loading of glass-infiltrated alumina-based (IA, In-Ceram Alumina) and zirconia-reinforced (IZ, In-Ceram Zirconia) ceramics, testing the hypothesis that wet environment influences the SCG of both ceramics when submitted to cyclic loading. METHODS: Bar-shaped specimens of IA (n=45) and IZ (n=45) were fabricated and loaded in three-point bending (3P) in 37 degrees C artificial saliva (IA(3P) and IZ(3P)) and cyclic fatigued (F) in dry (D) and wet (W) conditions (IA(FD), IA(FW), IZ(FD), IZ(FW)). The initial sigma and the number of cycles to fracture were obtained from 3P and F tests, respectively. Data was examined using Weibull statistics. The SCG behavior was described in terms of crack velocity as a function of maximum stress intensity factor (K(Imax)). RESULTS: The Weibull moduli (m=8) were similar for both ceramics. The characteristic strength (sigma(0)) of IA and IZ was and 466MPa 550MPa, respectively. The wet environment significantly increased the SCG of IZ, whereas a less evident effect was observed for IA. In general, both ceramics were prone to SCG, with crack propagation occurring at K(I) as low as 43-48% of their critical K(I). The highest sigma of IZ should lead to longer lifetimes for similar loading conditions. SIGNIFICANCE: Water combined with cyclic loading causes pronounced SCG in IZ and IA materials. The lifetime of dental restorations based on these ceramics is expected to increase by reducing their direct exposure to wet conditions and/or by using high content zirconia ceramics with higher strength. PMID- 20303161 TI - Brief report: the number of sexual partners and race-related stress in African American adolescents: preliminary findings. AB - The current study examined the association between the number of lifetime sexual partners and race-related stress among African American 201 high school juniors and seniors at two urban high schools in the Southeastern region of the country. Students completed the Index of Race-Related Stress-Brief (IRRS-B) and the Youth Risk Behavior Survey (YRBS). African American male adolescents reported higher race-related stress and a higher number of sexual partners compared to African American females. Controlling for gender and age of first intercourse, race related stress significantly predicted the number of sexual partners for African American adolescents. Preliminary findings indicate that the role of race-related stress may prove critical in decreasing risky sexual behavior among African American adolescents. PMID- 20303162 TI - The psychological impact of peer victimization: exploring social-cognitive mediators of depression. AB - Although the association between peer victimization and depression is well established (Hawker & Boulton, 2000; Nansel et al., 2001), little research has examined the processes whereby victimization may lead to depression. This study examined the social-cognitive processes that mediate the relationship between peer victimization and depression. A questionnaire measuring peer victimization, depression, depression rumination, self efficacy to enlist support, and collective school efficacy to stop peer aggression at two time points during one school year was completed by 1167 secondary school children. Rumination, collective school efficacy and self efficacy to enlist support from a friend partially mediated the relationship between victimization and depression. Children who were victimized ruminated more, which lead to increased levels of depression. Victims were also less likely to believe that students and teachers could work together to stop peer aggression, which impacted their propensity to access the support of friends leading to higher depression. PMID- 20303163 TI - Glycyrrhetinic acid-modified chitosan/poly(ethylene glycol) nanoparticles for liver-targeted delivery. AB - A liver-targeted drug delivery carrier, composed of chitosan/poly(ethylene glycol)-glycyrrhetinic acid (CTS/PEG-GA) nanoparticles, was prepared by an ionic gelation process, in which glycyrrhetinic acid (GA) acted as the targeting ligand. The formation and characterization of these nanoparticles were confirmed by FT-IR, dynamic light scattering (DLS) and zeta potential measurements. The biodistribution of the nanoparticles was assessed by single-photon emission computed tomography (SPECT), and the cellular uptake was evaluated using human hepatic carcinoma cells (QGY-7703 cells). The anti-neoplastic effect of the doxorubicin.HCl-loaded nanoparticles (DOX-loaded nanoparticles) was also investigated in vitro and in vivo. The results showed that the CTS/PEG-GA nanoparticles were remarkably targeted to the liver, and keep at a high level during the experiment. The accumulation in the liver was 51.3% at 3 h after injection; this was nearly 2.6 times that obtained with the CTS/PEG nanoparticles. The DOX-loaded nanoparticles were greatly cytotoxic to QGY-7703 cells, and the IC(50) (50% inhibitory concentration) for the free doxorubicin.HCl (DOX.HCl) and the DOX-loaded CTS/PEG-GA nanoparticles were 47 and 79 ng/mL, respectively. Moreover, the DOX-loaded CTS/PEG-GA nanoparticles could effectively inhibit tumor growth in H22 cell-bearing mice. PMID- 20303164 TI - Effects of cleavable PEG-cholesterol derivatives on the accelerated blood clearance of PEGylated liposomes. AB - The "accelerated blood clearance" (ABC) phenomenon describes a syndrome whereby the circulation time of a second dose of injected liposomes is substantially reduced, while the hepatic and splenic accumulations increase. To avoid this unexpected immune response, we have modified liposomes with cleavable PEG-lipid derivatives (PEG-CHEMS and PEG-CHMC). The ABC phenomenon was induced by repeated injection of conventional PEG-DSPE-liposomes in rat body and was accompanied by a greatly increased uptake in the liver. In contrast, only a slight ABC phenomenon was induced by repeated injection of PEG-CHMC-liposomes and was accompanied by increased uptake in the liver. Repeated injection of PEG-CHEMS-liposomes did not induce either an ABC phenomenon or an increase in liver accumulation. Repeated injection of the cleavable PEG-lipid modified vesicles (tris (hydroxymethyl) aminomethane salt of cholesteryl hemisuccinate(CHST)) showed similar results to those found with the cleavable PEG-lipid modified liposomes. These cleavable PEG lipid derivatives could lessen or eliminate the ABC phenomenon produced by repeated injection of PEGylated liposomes or vesicles. Consequently, these two cleavable PEG-lipid derivatives may not only prolong the circulation time of nanoparticles, but may also represent a solution to the ABC phenomenon. PMID- 20303165 TI - Imaging and inhibition of multi-drug resistance in cancer cells via specific association with negatively charged CdTe quantum dots. AB - Photoluminescent semiconductor quantum dots (QDs) have received significant attention in biological and biomedical fields because of their attractive properties. In this contribution, we have explored and evaluated the utilization of water-soluble nanocrystal CdTe quantum dots (QDs) capped with negatively charged 3-mercapitalpropionic acid (MPA)-QDs to enhance the drug uptake into the target cancer cells and the efficiency of the biomarker and cancer treatments, by using the cytotoxicity evaluation, total internal reflection fluorescence microscopy, electrochemistry and UV-Vis absorption spectroscopy. Our results illustrate that the MPA-CdTe QDs could effectively facilitate the interaction of anticancer agent daunorubicin (DNR) with leukemia cells and the efficiency of biolabeling in cancer cells. Therefore, the present study affords a new potential method for simultaneous cellular inhibition and imaging of cancer cells. PMID- 20303166 TI - Nucleic acid transfer with hemifluorinated polycationic lipids. AB - In this study, the ability of synthetic fluorinated lipospermines to bind DNA and siRNA was investigated and the transfection efficiency and toxicity of the resulting lipoplexes in cell lines were evaluated. Three lipopolyamines displaying fluorous tags close to their cationic polar head ("HFP" polyamines) were synthesized. Their ability to condense pDNA and siRNA, and to form nanoparticles were characterized. Lipoplex stability was investigated in the presence of different surface active compounds and was shown to be significantly improved due to the presence of the fluorous tags. Transfection efficiencies were studied in HepG2 and 911 cell lines, and compared to that of DOGS, DOTAP, and Lipofectamine 2000. Also, the ability of these compounds to deliver nucleic acids into cells in the presence of high concentration of serum was quantified. By incorporating two fluorous tags in the direct vicinity of the polycationic head group of the lipospermines, we show efficient pDNA and siRNA formulation, and delivery to cultured cells. Fluorinated lipoplexes exhibit improved stability in the presence of amphiphilic compounds and retain high transfection efficiency in the presence of 50-75% serum. These results demonstrate that lipospermines displaying fluorous tags close to their cationic polar head bind to and deliver pDNA and siRNA with high cell viability in different cell lines. They are efficient non-viral vectors that exhibit remarkable serum compatibility. PMID- 20303167 TI - Mesoporous carbide-derived carbon for cytokine removal from blood plasma. AB - Porous carbons can be used for purification of bio-fluids due to their excellent biocompatibility with blood. Since the ability to adsorb a range of inflammatory cytokines within the shortest possible time is crucial to stop the progression of sepsis, the improvement of the adsorption rate is a key factor to achieving efficient removal of cytokines. Here, we demonstrate the effect of synthesis temperatures (from 600 degrees C to 1200 degrees C), carbon particle sizes (from below 35 microm to 300 microm), and annealing conditions (Ar, NH(3), H(2), Cl(2), and vacuum annealing) that determine the surface chemistry, on the ability of carbide-derived carbons (CDCs) to remove cytokines TNF-alpha, IL-6, and IL-1 beta from blood plasma. Optimization of CDC processing and structure leads to up to two orders of magnitude increase in the adsorption rate. Mesoporous CDCs that were produced at 800 degrees C from Ti(2)AlC with the precursor particle size of <35 microm and annealed in NH(3), displayed complete removal of large molecules of TNF-alpha in less than an hour, with >85% and >95% TNF-alpha removal in 5 and 30 min, respectively. This is a very significant improvement compared to the previously published results for CDC (90% TNF-alpha removal after 1h) and activated carbons. Smaller interleukin IL-6 and IL-1 beta molecules can be completely removed within 5 min. These differences in adsorption rates show that carbons with controlled porosity can also be used for separation of protein molecules. PMID- 20303168 TI - The role of cyclic AMP in normalizing the function of engineered human blood microvessels in microfluidic collagen gels. AB - Nearly all engineered tissues must eventually be vascularized to survive. To this end, we and others have recently developed methods to synthesize extracellular matrix-based scaffolds that contain open microfluidic networks. These scaffolds serve as templates for the formation of endothelial tubes that can be perfused; whether such microvascular structures are stable and/or functional is largely unknown. Here, we show that compounds that elevate intracellular concentrations of the second messenger cyclic AMP (cAMP) strongly normalize the phenotype of engineered human microvessels in microfluidic type I collagen gels. Cyclic AMP elevating agents promoted vascular stability and barrier function, and reduced cellular turnover. Under conditions that induced the highest levels of cAMP, the physiology of engineered microvessels in vitro quantitatively mirrored that of native vessels in vivo. Computational analysis indicated that cAMP stabilized vessels partly via its enhancement of barrier function. PMID- 20303170 TI - In vivo study of an injectable poly(acrylonitrile)-based hydrogel paste as a bulking agent for the treatment of urinary incontinence. AB - Urinary incontinence can be treated by endoscopic injection of bulking agents, however, no optimal therapeutic effect has been achieved upon this treatment yet. In the present study, the development of a injectable poly(acrylonitrile) hydrogel paste is described, and its efficacy and histological behavior, once injected into the submucosal space of the minipig bladder, are evaluated. A device was developed to mix poly(acrylonitrile) hydrogel powder with glycerin, used as carrier, prior to injection into the submucosal space of the bladder. Several paste deposits, depending on the size of the bladder, were injected per animal. The implants were harvested at days 7, 14, 21, 28, 84 and 168 and analyzed morphologically and by histology. The persistence of the implants was demonstrated. However, at later time points the implants were split up and surrounded by granulomatous tissue, which was gradually replaced by histiocytes and adipocytes. Transitory focal urothelial metaplasia was observed only at day 7 and moderate foreign body reaction was detected predominantly between the second and fifth week. This study demonstrated the feasibility to develop an injectable paste of poly(acrylonitrile) hydrogel thought to provide the expected bulking effect, necessary for the treatment of urinary incontinence. PMID- 20303171 TI - Egr-1-A Ca(2+)-regulated transcription factor. AB - The biosynthesis of the zinc finger transcription factor Egr-1 is stimulated by many extracellular signaling molecules including hormones, neurotransmitters, growth and differentiation factors. The Egr-1 gene represents a convergence point for many intracellular signaling cascades. An increase of the intracellular Ca(2+) concentration, by activating ionotropic or Galpha(q/11)-coupled receptors or voltage-gated L-type Ca(2+) channels, is often the prerequisite for enhanced Egr-1 gene transcription. This increase has been observed following stimulation with extracellular signaling molecules including ATP, glutamate, thrombin, carbachol, gonadotropin-releasing hormone, or glucose. Egr-1 is thus a Ca(2+) regulated transcription factor - similar to CREB, NFAT, NF-kappaB and others. This review also discusses the importance of the cytoplasmic and nuclear Ca(2+) concentration in transcriptional regulation of the Egr-1 gene. PMID- 20303172 TI - Successful treatment of imatinib-resistant hypereosinophilic syndrome with nilotinib. PMID- 20303173 TI - A distinct expression of various gene subsets in CD34+ cells from patients with early and advanced myelodysplastic syndrome. AB - Gene expression profiles of CD34+ cells were compared between 51 MDS patients and 7 controls. The most up-regulated genes in patients included HBG2, HBG1, CYBRD1, HSPA1B, ANGPT, and MYC, while 13 genes related to B-lymphopoiesis showed down regulation. We observed in advanced MDS patients decreased expression of genes involved in cell cycle control, DNA repair and increased expression of proto oncogenes, angiogenic and anti-apoptic genes. The results suggest that increased cell proliferation and resistance to apoptosis together with a loss of cell cycle control, damaged DNA repair and altered immune response may play an important role in malignant clone expansion in MDS. PMID- 20303169 TI - Bioactive modification of poly(ethylene glycol) hydrogels for tissue engineering. AB - In this review, we explore different approaches for introducing bioactivity into poly(ethylene glycol) (PEG) hydrogels. Hydrogels are excellent scaffolding materials for repairing and regenerating a variety of tissues because they can provide a highly swollen three-dimensional (3D) environment similar to soft tissues. Synthetic hydrogels like PEG-based hydrogels have advantages over natural hydrogels, such as the ability for photopolymerization, adjustable mechanical properties, and easy control of scaffold architecture and chemical compositions. However, PEG hydrogels alone cannot provide an ideal environment to support cell adhesion and tissue formation due to their bio-inert nature. The natural extracellular matrix (ECM) has been an attractive model for the design and fabrication of bioactive scaffolds for tissue engineering. ECM-mimetic modification of PEG hydrogels has emerged as an important strategy to modulate specific cellular responses. To tether ECM-derived bioactive molecules (BMs) to PEG hydrogels, various strategies have been developed for the incorporation of key ECM biofunctions, such as specific cell adhesion, proteolytic degradation, and signal molecule-binding. A number of cell types have been immobilized on bioactive PEG hydrogels to provide fundamental knowledge of cell/scaffold interactions. This review addresses the recent progress in material designs and fabrication approaches leading to the development of bioactive hydrogels as tissue engineering scaffolds. PMID- 20303174 TI - The role of trauma symptoms in the development of behavioral problems in maltreated preschoolers. AB - OBJECTIVE: This study assessed the mediating role of trauma symptoms in the relation between child maltreatment and behavioral problems. It is based on the postulate that child maltreatment is a severe form of chronic relational trauma that has damaging consequences on the development of children's behavioral regulation. METHOD: Participants were 34 maltreated and 64 non-maltreated children (mean age=60 months; range: 46 to 72 months), all from economically disadvantaged families. Maltreated children were recruited from the Child Protection Agencies. Behavioral problems and trauma symptoms were evaluated by the preschool teacher with the Internalizing and the Externalizing scales of the Child Behavior Checklist-Teacher Report Form (CBCL-TRF) and the posttraumatic stress score of the Trauma Symptoms Checklist for Young Children respectively (TSCYC). RESULTS: Baron and Kenny's mediational procedure was conducted using structural equation modeling. Mediational analyses revealed that trauma symptoms fully mediated the association between maltreatment and both internalizing and externalizing behaviors. CONCLUSIONS: Results were consistent with the literature on developmental trauma research and provide empirical support to the idea that trauma-related symptoms resulting from early maltreatment may constitute a mechanism in the development of psychosocial problems in preschoolers. PRACTICE IMPLICATIONS: These findings underline the importance of understanding psychosocial maladjustment of maltreated children not only from the perspective of problematic behavior, but also by taking into account the traumatic reactions that might develop in response to chronic and intense stress associated with abuse and neglect. PMID- 20303175 TI - Beneficial effect of pine honey on trichlorfon induced some biochemical alterations in mice. AB - Forty-eight male BALB/c mice, weighing 30-35 g, were used in the study, and were divided into groups of 12 each. The four groups established in the study included one control group and three experimental groups. The first group served as the control group, while Groups 2, 3 and 4 were administered 1g/kg bw/day pine honey, 180 mg/kg bw/day trichlorfon ( approximately 1/5LD(50)) and 1g/kg bw/day pine honey plus 180 mg/kg bw/day trichlorfon, respectively, by the oral route using a catheter for 21 days. At the end of 21 days post-administration, blood and tissue (liver, kidney, brain and heart) samples were collected. Serum levels/activities of total protein, albumin, glucose, cholesterol, triglyceride, BUN, creatine, uric acid, magnesium, sodium, potassium, chloride, total bilirubin, GGT, LDH, AST, ALT and ALP were determined. Furthermore, tissue MDA levels and CAT, SOD and GSH-Px activities were analyzed. According to the data obtained, when administered at the indicated dose and for the indicated time period, trichlorfon was determined to lead to negative alterations in most of the biochemical parameters investigated. The administration of pine honey was determined to alleviate this effect. PMID- 20303176 TI - Challenges and strategies in applying performance measurement to federal public health programs. AB - Performance measurement is widely accepted in public health as an important management tool supporting program improvement and accountability. However, several challenges impede developing and implementing performance measurement systems at the federal level, including the complexity of public health problems that reflect multiple determinants and involve outcomes that may take years to achieve, the decentralized and networked nature of public health program implementation, and the lack of reliable and consistent data sources and other issues related to measurement. All three of these challenges hinder the ability to attribute program results to specific public health program efforts. The purpose of this paper is to explore these issues in detail and offer potential solutions that support the development of robust and practical performance measures to meet the needs for program improvement and accountability. Adapting performance measurement to public health programs is both an evolving science and art. Through the strategies presented here, appropriate systems can be developed and monitored to support the production of meaningful data that will inform effective decision making at multiple levels. PMID- 20303177 TI - Decision-makers' perspectives on the use of bioaccessibility for risk-based regulation of contaminated land. AB - Information on contaminant bioaccessibility has been recognized by researchers, legislators and regulators as a decision-support tool for contaminated land assessment and has been subject to interest and discussion at both national and international levels. A sustainable, proportionate and risk-based approach to contaminated land management has been adopted by contaminated land regimes throughout the world. While this approach guides national and international priorities, its practical implementation in many countries, including the United Kingdom, is reliant upon local authorities. Here, we present an investigation into the views of local authorities in England and Wales regarding the practical application of bioaccessibility and constraints associated with its implementation. The research involved an online survey followed by semi structured interviews with selected respondents. A majority of survey respondents (70%) perceived bioaccessibility to be a useful tool that facilitates contaminated land management. However, 76% of participants indicated a need for more information regarding bioaccessibility as well as emphasising a need for more research into polycyclic aromatic hydrocarbons. Lack of statutory guidance was indicated by 78% of respondents as the main factor hampering the use of bioaccessibility data in regulatory decision-making. Divergence of policy-maker and local regulator perceptions of bioaccessibility was also indicated by the respondents. This research brings the voice of front-line regulators for contaminated land into the on-going discussion between policy-makers and scientists on the uses of bioaccessibility. This study concludes by proposing action priorities both for the research community and for policy-makers, which are transferable to risk-based regimes elsewhere. PMID- 20303178 TI - Uranium isotopes in the Balkan's environment and foods following the use of depleted uranium in the war. AB - Immediately after the Balkan's war in 1999, there has been widespread international concern about the environmental contamination with depleted uranium (DU) from ammunitions used in the conflict. Exposure of military staff and local populations to uranium metal and to its ionizing radiation were feared as potential causes for leukemia and other diseases in that region. In January 2001 a scientific mission was carried out by Portugal to evaluate those issues. A large number of environmental and food samples collected in Kosovo and Bosnia Herzegovina, such as soils, water, aerosols, vegetables, bread, and meat were analyzed by radiochemistry and alpha spectrometry. Results of the analyses for total uranium and individual uranium isotopes are presented. Uranium in agriculture soils in Kosovo and Bosnia-Herzegovina averaged 1.8+/-0.8mgkg(-)(1) and 3+/-1mgkg(-)(1), while concentrations in drinking water from public supplies averaged 0.5+/-0.2microgL(-)(1) and 0.4+/-0.3microgL(-)(1), respectively. Results on soils indicated also that environmental contamination by DU was much localized and confined to the areas of ammunition impact. Concentrations of uranium in most of the environmental and food samples were comparable to concentrations of uranium measured in other European regions, such as Portugal and United Kingdom, and uranium isotopic ratios were in general compatible with isotopic ratios typical of natural uranium. However, a few samples displayed modified uranium isotopic ratios and could have been contaminated by DU. Implications of DU in radiation exposure of the population and in environmental contamination are discussed. PMID- 20303179 TI - TCR gene-engineered T cell: limited T cell activation and combined use of IL-15 and IL-21 ensure minimal differentiation and maximal antigen-specificity. AB - Clinical TCR gene therapy of melanoma represents a feasible and promising treatment rationale yet is currently challenged by objective response rates that stay behind those observed with conventional adoptive T cell therapy. Here, the phenotype and function of TCR-transduced T cells, considered to determine the efficacy of TCR gene therapy, were studied in relation to T cell activation and cytokine treatments. We observed that the lectin Concanavalin A (ConA), and to a lesser extent anti-CD3 and CD28 mAbs (soluble CD3/CD28), resulted in functional surface expression of the TCRalphabeta transgenes and enhanced fractions of CD62L(hi), CD44(lo) naive T cells. T cell functions and limited T cell differentiation were most significant when T cells were treated with a combination of IL-15 and IL-21 rather than IL-2. In comparison, anti-CD3 and CD28 mAbs coated to either latex or polystyrene beads (polystyrene or latex CD3/CD28) resulted in improved TCR expression levels and enhanced T cell differentiation irrespective of cytokine treatment, with effects most pronounced for polystyrene CD3/CD28. T cells demonstrated enhanced cytotoxic activity and IFNgamma production when activated with CD3/CD28 beads and treated with IL-15 and IL-21, but at the same time displayed non-specific T cell responses. In contrast, ConA and soluble CD3/CD28 activations resulted in antigen-specific T cell responses. In short, we show that retroviral TCR engineering of primary T cells benefits from activation with ConA or soluble CD3/CD28 rather than immobilized anti-CD3 and CD28 mAbs with respect to T cell differentiation and antigen-specificity of T cell responses. PMID- 20303180 TI - Alexithymia is associated with anxiety among adolescents. AB - BACKGROUND: The aim of this study was to explore the possible association between alexithymia and anxiety in a non-clinical sample of late adolescents. METHODS: The questionnaire was sent to 935 adolescents of whom 729 (78%) responded, thus forming the final sample. The mean age of the subjects was 19 years (range 17-21 years). The Finnish versions of the following scales were used: the 20-item Toronto Alexithymia Scale (TAS-20) was used to assess alexithymia, and anxiety symptoms were measured using the State-Trait Anxiety Inventory (STAI). Alcohol consumption was assessed using the Alcohol Use Disorders Identification Test (AUDIT), and depression symptoms were evaluated using the short form of the Beck Depression Inventory, as modified by Raitasalo (RBDI). RESULTS: The prevalence of alexithymia in the sample was 8.2%, with no statistically significant gender difference. The alexithymic subjects had significantly (p<0.001) higher mean STAI scores than the non-alexithymic subjects. A vast majority of the alexithymic subjects were highly anxious, in contrast to the low proportion among the non alexithymic subjects. The highly anxious alexithymic subjects differed statistically and significantly from the highly anxious non-alexithymic subjects, with higher scores both in the AUDIT and the RBDI. LIMITATIONS: The results are based on self-reported material alone and the cross-sectional design used in this study precludes the assessment of causal links. CONCLUSIONS: The results suggest that anxiety symptoms are independently associated with alexithymia among late adolescents in general population. PMID- 20303181 TI - Depression in Asian-American and Caucasian undergraduate students. AB - BACKGROUND: Depression is a serious and often under-diagnosed and undertreated mental health problem in college students which may have fatal consequences. Little is known about ethnic differences in prevalence of depression in US college campuses. This study compares depression severity in Asian-American and Caucasian undergraduate students at the University of California San Diego (UCSD). METHODS: Participants completed the nine item Patient Health Questionnaire and key demographic information via an anonymous online questionnaire. RESULTS: Compared to Caucasians, Asian-Americans exhibited significantly elevated levels of depression. Furthermore, Korean-American students were significantly more depressed than Chinese-American, other minority Asian-American, and Caucasian students. In general, females were significantly more depressed than males. Results were upheld when level of acculturation was considered. LIMITATIONS: The demographic breakdown of the student population at UCSD is not representative to that of the nation. CONCLUSIONS: These findings suggest that outreach to female and Asian-American undergraduate students is important and attention to Korean-American undergraduates may be especially worthwhile. PMID- 20303182 TI - Expression of the avian-specific toll-like receptor 15 in chicken heterophils is mediated by gram-negative and gram-positive bacteria, but not TLR agonists. AB - Toll-like receptors (TLRs) are a critical component of the innate immune response of mammalian and avian species. While most mammalian TLRs have been well characterized, the chicken-specific TLR15 has not been extensively studied. We recently demonstrated that TLR15 is differentially expressed between Salmonella susceptible-and-resistant chickens, indicating a potential role in the innate immune response to infection with Salmonella. The aim of the present study was to gain better insight into the nature of the ligand for TLR15 by characterizing gene expression patterns of TLR15 by heterophils in response to numerous bacterial-derived TLR agonists LPS, flagellin, CpG oligodeoxynucleotides, lipotechoic acid (LTA), peptidoglycan (PGN), and Pam3CSK4 (PAM), stimulation with live Salmonella enterica serovar Enteritidis (SE-used as a positive control), chicken isolates of Escherichia coli (EC) and Enterococcus gallinarum (EG), the equine-specific pathogen Rhodococcus equi, and stimulation with heat-killed, and formalin-killed SE, EC, and EG. TLR15 expression increased significantly in response to stimulation with live, heat-killed and formalin-killed SE, EC, and EG, but was unaffected by stimulation with known TLR agonists and R. equi. Overall, these observations demonstrate that the individual TLR agonists are not the ligand for TLR15, and that TLR15 recognizes a unique, non-secreted, heat stabile component of both Gram-negative and Gram-positive bacteria commonly found in and/or capable of causing disease in chickens. PMID- 20303184 TI - Changes in serum IGF-1 and IGFBP-3 levels and growth in children following adenoidectomy, tonsillectomy or adenotonsillectomy. AB - OBJECTIVE: The aim of this study is to determine the effect of adenoidectomy, tonsillectomy or adenotonsillectomy on growth. For this purpose, we prospectively reviewed the postoperative changes in serum levels of insulin-like growth factor 1 (IGF-1) and insulin-like growth factor binding protein-3 (IGFBP-3), weight and height in children that underwent adenoidectomy, tonsillectomy or adenotonsillectomy. METHODS: Ninety-six children with symptoms of sleep disordered breathing (SDB) or recurrent adenotonsillitis were enrolled to study. Blood samples were taken preoperatively and repeated at 6 months following operation to determine the changes in serum IGF-1 and IGFBP-3 levels, pre- and postoperative values of weight and height were recorded for each operation. RESULTS: Thirty-six patients underwent adenoidectomy, 52 patients underwent adenotonsillectomy and 8 patients underwent tonsillectomy. Seventy of the operations were performed for SDB and 26 were performed for recurrent adenotonsillitis. The mean serum levels of IGF-1 increased by 26%, from 126.74+/ 112.13 ng/ml to 159.82+/-122.91 ng/ml (p<0.001) and IGFBP-3 levels increased by 7%, from 3.34+/-1.17 microg/l to 3.57+/-1.16 microg/l (p<0.05) 6 months after operation. The increase was independent from the preoperative diagnosis. There was a significant increase both in patients with SDB and in children with recurrent infections (p<0.001 for IGF-1, p<0.05 for IGFBP-3). Their Z scores (standard deviation scores) for body weights (mean Z score from -0.06+/-0.98 to 0.118+/-1.18, p<0.001) and heights (mean Z score from 0.30+/-0.98 to 0.42+/-0.88, p<0.001) were significantly higher 6 months after the operation compared to preoperative period. CONCLUSIONS: We found a significant increase in weight, height, and IGF-1 and IGFBP-3 levels of children with SDB or recurrent infections postoperatively. These results suggest that upper airway obstruction may not be the only mechanism that causes retardation on growth in children. PMID- 20303183 TI - Absence of PI3Kgamma leads to increased leukocyte apoptosis and diminished severity of experimental autoimmune encephalomyelitis. AB - Phosphatidylinositol-3-kinase gamma (PI3Kgamma) plays an important role in the motility of leukocytes in several models of inflammation. In this work, the role of PI3Kgamma in experimental autoimmune encephalomyelitis (EAE) was investigated. EAE was induced in wild-type and PI3Kgamma deficient mice (PI3Kgamma(-)(/)(-)). WT animals had a peak of clinical symptoms around day 14 post-induction (p.i.). PI3Kgamma(-)(/)(-) animals developed milder EAE signs and peak of disease was noticed only on day 21 p.i. Better clinical outcome correlated with the absence of perivascular cuffs on day 14 p.i. and with decreased levels of CCL2 and CCL5 in brain of PI3Kgamma(-)(/)(-) mice. There was increased leukocyte rolling and adhesion in pial vessels, as assessed by intravital microscopy, at day 14 after EAE induction in WT mice. The latter parameters were unaltered in PI3Kgamma( )(/)(-) mice subjected to EAE. Moreover, the PI3Kgamma inhibitor AS-605240 given just before the intravital microscopy failed to affect leukocyte rolling or adhesion. Finally, there was a significant increase in the number of apoptotic cells in the CNS of EAE-induced PI3Kgamma(-/-) mice. Our results suggest that PI3Kgamma is involved in EAE and plays a more important role in mediating leukocyte survival than leukocyte adhesion in this experimental model of multiple sclerosis. PMID- 20303185 TI - Threshold prediction in children with sensorioneural hearing loss using the auditory steady-state responses and tone-evoked auditory brain stem response. AB - OBJECTIVE: The purpose of this study was to compare ASSRs to tone-evoked ABR and to behavioral thresholds obtained on follow-up audiometry at 500, 1000, 2000, and 4000 Hz in infants and young children. METHODS: The study included 17 infants and young children ages between 2 months and 3 years old, with sensorineural hearing loss. The ASSRs thresholds were compared with the tone-evoked ABR thresholds, and with the behavioral thresholds obtained on follow-up audiometry. RESULTS: The correlation of tone-evoked ABR and ASSRs thresholds at 500, 1000, 2000 and 4000 Hz was 0.91, 0.76, 0.81, 0.89, respectively. ASSRs and behavioral hearing thresholds obtained on follow-up were highly correlated, with Pearson r values exceeding 0.94 at each of the test frequencies. CONCLUSIONS: Multiple ASSRs have strong correlations to tone-evoked ABR and to behavioral thresholds obtained during follow-up in hearing impaired infants and young children. These results might be useful in order to provide further evidence for the use of multiple ASSRs, as an alternative tool to tone-evoked ABR, although further data are still required. PMID- 20303186 TI - Signaling by internalized G-protein-coupled receptors. AB - G-protein-coupled receptors (GPCRs) are cell surface receptors and are generally assumed to signal to second messengers such as cyclic AMP (cAMP) exclusively from the plasma membrane. However, recent studies indicate that GPCRs can continue signaling to cAMP after internalization together with their agonists. Signaling from inside the cell is persistent and appears to trigger specific downstream effects. Here, we will review these recent data, which form the basis for a novel concept of intracellular GPCR signaling and suggest new and intriguing scenarios for the functions of GPCRs in the endocytic compartment. We propose that current models of GPCR signaling should be revised to accommodate the ability of receptors to change their signaling properties depending on their subcellular localization. PMID- 20303188 TI - Assessment of uptake and toxicity of fluorescent silica nanoparticles in zebrafish (Danio rerio) early life stages. AB - In this study, we determined uptake and toxicity of fluorescent core-shell silica nanoparticles (FSNP) in early life stages of zebrafish. For this purpose fluorescent Ru@SiO2 nanoparticles with average size of ~200 nm encapsulating [Ru(bpy)3](2+)Cl2 dye (excitation wavelength lambda(exci)=488 nm), and Cy5.5@SiO2 with average size of ~60 nm (lambda(exci)=700 nm) were synthesized. The FSNP were highly luminescent. Field emission SEM analysis showed monodispersed dual-shell Ru@SiO2 nanoparticles of ~200 nm size. Zebrafish embryos were exposed less than 6h post-fertilization (hpf) to the ~60 and ~200 nm FSNP at concentrations between 0.0025 and 200mg/L in 24-well plates for up to 96 hpf. The concentrations were analysed using an Fourier transform infra-red (FTIR) technique. Uptake of FSNP by embryos was monitored using transmission and confocal fluorescence microscopy. Toxicity was assessed by mortality, hatching time and success, and by morphological alterations. The ~60 and ~200 nm-sized FSNP and/or aggregates were adsorbed on the chorion of eggs. Uptake and translocation in embryos was not observed, but nanoparticle uptake not detectable by confocal microscopy may have occurred. Hatching time and hatching success were not affected. No mortality or deformities occurred. These nanoparticles and/or aggregates mainly accumulate on the chorion of embryos and exhibit no overt embryotoxicity. PMID- 20303189 TI - Percutaneous aortic valve in severe valvular regurgitation caused by infective endocarditis. AB - Recently, the feasibility and safety of percutaneous aortic valve replacement (PAVR) have been reported in the treatment of degenerative aortic valve stenosis in patients at high-risk for surgical aortic valve replacement (AVR). However, so far this therapy has been limited to patients with severe stenosis of the native valve. We report the case of an 84 year old patient with severe aortic regurgitation caused by infective endocarditis who was successfully treated by implantation of a CoreValve (CoreValve Inc, Irvine. Calif) prosthesis with a totally percutaneous approach. PMID- 20303187 TI - Spatially restricting gene expression by local translation at synapses. AB - mRNA localization and regulated translation provide a means of spatially restricting gene expression within each of the thousands of subcellular compartments made by a neuron, thereby vastly increasing the computational capacity of the brain. Recent studies reveal that local translation is regulated by stimuli that trigger neurite outgrowth and/or collapse, axon guidance, synapse formation, pruning, activity-dependent synaptic plasticity, and injury-induced axonal regeneration. Impairments in the local regulation of translation result in aberrant signaling, physiology and morphology of neurons, and are linked to neurological disorders. This review highlights current advances in understanding how mRNA translation is repressed during transport and how local translation is activated by stimuli. We address the function of local translation in the context of fragile X mental retardation. PMID- 20303191 TI - Diagnostic sampling strategies for virulent ovine footrot: simulating detection of Dichelobacter nodosus serogroups for bivalent vaccine formulation. AB - Dichelobacter nodosus is a slow-growing anaerobic bacterium that is the causative agent of virulent ovine footrot. Vaccination targeted at up to two specific serogroups can eliminate those serogroups from infected flocks, but requires identification of serogroups present in infected flocks. Serogroups can be identified using slide agglutination or polymerase chain reaction (PCR) methods. The objectives of this project were to use stochastic simulation modeling to estimate the efficacy of sampling strategies encompassing 5-40 sheep per flock and 2-4 colonies per sheep, and to compare efficacies based on slide agglutination or multiplex PCR test results. Foot swabs collected from sheep in 12 flocks were used as the basis for a sampling strategy simulation model. None of the evaluated sampling strategies identified the two most common serogroups in the flock, or all serogroups present in the flock, in 95% of iterations. However, a simulated sample of 22 sheep/flock and 2 colonies/sheep resulted in a simulated vaccine that protected 95% of the sheep that could be protected by a single bivalent vaccine, while a sample of 24 sheep/flock and 2 colonies/sheep resulted in a series of simulated bivalent vaccines that protected 95% of diseased infected sheep. The difference in outcome was due to the distribution and frequency of serogroups within certain flocks where some serogroups were uncommon and others dominant. A sampling strategy (>40 sheep/flock, 4 colonies/sheep) that will identify the two most common serogroups in a flock 95% of the time may not be cost effective. Evaluating efficacy based on the expected effect on the flock may be more useful than one which seeks to determine the most common serogroups. These findings are broadly applicable to diseases where more than one strain or type of pathogen may be present and must be represented in a vaccine. PMID- 20303190 TI - Lipoprotein(a) is strongly associated with coronary artery calcification in type 2 diabetic women. AB - BACKGROUND: Lp(a), implicated in both atherogenesis and thrombosis pathways, varies significantly by demographic and metabolic factors, providing challenges for its use in Coronary Heart Disease (CHD) risk. The purpose of this study was to investigate whether type-2 diabetic subjects, relative to non-diabetics, might benefit more from Lp(a) measurement in the prediction of CHD risk, as measured by coronary artery calcium (CAC). METHODS: We performed cross sectional analyses in two community-based studies: the Penn Diabetes Heart Study [N = 1299 with type-2 diabetes] and the Study of Inherited Risk of Coronary Atherosclerosis [N = 860 without diabetes]. RESULTS: Blacks had 2-3 fold higher Lp(a) levels than whites in diabetic and non-diabetic samples. There was significant difference by gender (interaction p<0.001), but not race, in the association of Lp(a) with CAC in type 2 diabetic subjects. In age and race adjusted analysis of diabetic women, Lp(a) was associated with CAC [Tobit regression ratio 2.76 (95% CI 1.73-4.40), p<0.001]. Adjustment for exercise, medications, Framingham risk score, metabolic syndrome, BMI, CRP and hemoglobin A1c attenuated this effect, but the association of Lp(a) with CAC remained significant [2.25, (1.34-3.79), p = 0.002]. This relationship was further maintained in women stratified by race, or by the use of HRT or lipid lowering drugs. In contrast, Lp(a) was not associated with CAC in diabetic men, nor in non-diabetic men and women. CONCLUSIONS: Lp(a) is a strong independent predictor of CAC in type-2 diabetic women, regardless of race, but not in men. Lp(a) does not relate to CAC in men or women without type-2 diabetes. PMID- 20303192 TI - Evaluation of suspension array analysis for detection of egg yolk antibodies against Salmonella Enteritidis. AB - Salmonella enterica serovar Enteritidis (SE) is an important source of food related diarrhoea in humans, and table eggs are considered the primordial source of contamination of the human food chain. Using eggs collected at egg-packing stations as samples could be a convenient strategy to detect colonization of layer flocks. The aim of this study was to evaluate egg yolk anti-Salmonella antibody detection using suspension array analysis. An egg yolk panel from contact-infected and non-colonized laying hens was used for the evaluation. Receiver Operating Characteristic (ROC) curves were generated to define a cut-off value and to assess the overall accuracy of the assay. The diagnostic sensitivity and specificity were estimated by maximum likelihood. Sensitivity was quantified on hen level and on sample level, and also quantified as a function of time since colonization. The area under the ROC curve was estimated at 0.984 (se 0.006, P<0.001). Of all colonized contact-infected hens, 67.6% [95% CI: 46.8, 100] developed an antibody response, which was detectable 17.4 days [14.3, 26.9] after colonization. In total, 98% [95.4, 99.4] of the 'immunopositive' hens had test positive eggs. The overall sensitivity of the immunological test was 66.7% [45.9, 98.7] and the specificity was 98.5% [97.8, 99.1]. This study provided essential parameters for optimizing surveillance programs based on detection of antibodies, and indicates that immunology based on examination of egg yolk gives important information about the Salmonella status of the flock. PMID- 20303193 TI - Rectal dose variation during the course of image-guided radiation therapy of prostate cancer. AB - BACKGROUND AND PURPOSE: To investigate the change in rectal dose during the treatment course for intensity-modulated radiotherapy (IMRT) of prostate cancer with image-guidance. MATERIALS AND METHODS: Twenty prostate cancer patients were recruited for this retrospective study. All patients have been treated with IMRT. For each patient, MR and CT images were fused for target and critical structure delineation. IMRT treatment planning was performed on the simulation CT images. Inter-fractional motion during the course of treatment was corrected using a CT on-rails system. The rectum was outlined on both the original treatment plan and the subsequent daily CT images from the CT-on-rails by the same investigator. Dose distributions on these daily CT images were recalculated with the isocenter shifts relative to the simulation CT images using the leaf sequences/MUs based on the original treatment plan. The rectal doses from the subsequent daily CTs were compared with the original doses planned on the simulation CT using our clinical acceptance criteria. RESULTS: Based on 20 patients with 139 daily CT sets, 28% of the subsequent treatment dose distributions did not meet our criterion of V(40) < 35%, and 27% did not meet our criterion of V(65) < 17%. The inter-fractional rectal volume variation is significant for some patients. CONCLUSIONS: Due to the large inter-fractional variation of the rectal volume, it is more favorable to plan prostate IMRT based on an empty rectum and deliver treatment to patients with an empty rectum. Over 70% of actual treatments showed better rectal doses than our clinical acceptance criteria. A significant fraction (27%) of the actual treatments would benefit from adaptive image-guided radiotherapy based on daily CT images. PMID- 20303194 TI - Differentiation between probiotic and wild-type Bacillus cereus isolates by antibiotic susceptibility test and Fourier transform infrared spectroscopy (FT IR). AB - Animal feed often contains probiotic Bacillus strains used as feed additives. Spores of the non-pathogenic B. cereus var. toyoi (product name Toyocerin) are used. Distinguishing between toxic wild-type Bacillus cereus strains and this probiotic strain is essential for evaluating the quality and risk of feed. Bacillus cereus CIP 5832 (product name Paciflor was used as probiotic strain until 2001. The properties of the two probiotic strains are quite similar. Differentiating between probiotic strains and wild-type B. cereus strains is not easy. ss-lactam antibiotics such as penicillin and cefamandole exhibit an inhibition zone in the agar diffusion test of probiotic B. cereus strains which are not seen for wild-type strains. Therefore, performing the agar diffusion test first may make sense before FT-IR testing. When randomly checking these strains by Fourier transform infrared spectroscopy (FT-IR), the probiotic B. cereus strains were separated from wild-type B. cereus/B. thuringiensis/B. mycoides/B. weihenstephanensis strains by means of hierarchical cluster analysis. The discriminatory information was contained in the spectral windows 3000-2800 cm(-1) ("fatty acid region"), 1200-900 cm(-1) ("carbohydrate region") and 900-700 cm(-1) ("fingerprint region"). It is concluded that FT-IR spectroscopy can be used for the rapid quality control and risk analysis of animal feed containing probiotic B. cereus strains. PMID- 20303195 TI - Genetic analysis of the plantaricin EFI locus of Lactobacillus plantarum PCS20 reveals an unusual plantaricin E gene sequence as a result of mutation. AB - Lactobacillus plantarum strains produce a variety of chromosomally encoded bacteriocins and often multiple bacteriocins are encoded by a single strain. In this study, the genetic loci for bacteriocin production of L. plantarum strains BFE 5092 and PCS20 were studied. These strains were investigated for their possible application as protective cultures in food preservation. The bacteriocin locus of strain BFE 5092 showed remarkable similarity to the plantaricin loci previously described for L. plantarum strains C11 and WCFS1. However, the locus of the L. plantarum PCS20 strain was unusual in that it showed an interesting mutation as a result of deletions within the plnE gene. These deletions led to a hypothetically produced peptide which is 2 amino acids shorter than plantaricin E. Furthermore, it differs by 24 amino acids, while it shares 30 identical amino acids i.e., 15 at the amino end and 15 at the carboxyl end of the hypothetical peptide. As a consequence, the amino acid sequence is changed such that a double glycine-type leader peptide would not be encoded. This raises the question whether a functional peptide is being produced, even though RT-PCR studies showed that the plnE gene is obviously expressed. Furthermore, a transposase gene was located upstream of the plnEFI gene cluster and was inserted into a bacteriocin regulatory gene, the histidine protein kinase gene. Taken together, these facts indicate a loss of plantaricin gene function in L. plantarum PCS20 as a result of transposition and mutation. PMID- 20303196 TI - Attitudes towards mandatory national premarital screening for hereditary hemolytic disorders. AB - BACKGROUND: A compulsory national premarital screening (PMS) program for hereditary hemoglobinopathies was established in the Kingdom of Saudi Arabia (KSA) in February 2004. Termination of pregnancy of affected fetuses is not widely acceptable. Many couples decide to get married regardless of the result. A trend towards coercive interference with this decision is emerging. OBJECTIVES: To examine the attitude of young educated individuals regarding the national PMS program and its implementation. METHODS: Eight hundred university students (aged 18-29) filled in a self-administered structured questionnaire. Data were analyzed using the EPI Info Statistical Package version 6. A P-value <0.05 was considered significant. RESULTS: Most students favor the PMS program but there were concerns regarding mandating the testing and interference with individual decision making. Significantly more women favored testing and coercive interference with the decision to marry. CONCLUSIONS: Further public education and wide spread genetic counseling prior to testing is essential for the success of the program. Screening singles on admission to university prior to any commitment may be preferable than screening immediately before the marriage certificate is issued. PMID- 20303197 TI - Transcriptome profile analysis of floral sex determination in cucumber. AB - Cucumber has been widely studied as a model for floral sex determination. In this investigation, we performed genome-wide transcriptional profiling of apical tissue of a gynoecious mutant (Csg-G) and the monoecious wild-type (Csg-M) of cucumber in an attempt to isolate genes involved in sex determination, using the Solexa technology. The profiling analysis revealed numerous changes in gene expression attributable to the mutation, which resulted in the down-regulation of 600 genes and the up-regulation of 143 genes. The Solexa data were confirmed by reverse transcription polymerase chain reaction (RT-PCR) and real-time quantitative RT-PCR (qRT-PCR). Gene ontology (GO) analysis revealed that the differentially expressed genes were mainly involved in biogenesis, transport and organization of cellular component, macromolecular and cellular biosynthesis, localization, establishment of localization, translation and other processes. Furthermore, the expression of some of these genes depended upon the tissue and the developmental stage of the flowers of gynoecious mutant. The results of this study suggest two important concepts, which govern sex determination in cucumber. First, the differential expression of genes involved in plant hormone signaling pathways, such as ACS, Asr1, CsIAA2, CS-AUX1 and TLP, indicate that phytohormones and their crosstalk might play a critical role in the sex determination. Second, the regulation of some transcription factors, including EREBP-9, may also be involved in this developmental process. PMID- 20303198 TI - Treating headache recurrence after emergency department discharge: a randomized controlled trial of naproxen versus sumatriptan. AB - STUDY OBJECTIVE: Multiple parenteral medications are used to treat migraine and other acute primary headaches in the emergency department (ED). Regardless of specific headache diagnosis, no medication eliminates the frequent recurrence of primary headache after ED discharge. It is uncertain which medication primary headache patients should be given on discharge from an ED. The aim of this study is to compare the efficacy of oral sumatriptan with naproxen for treatment of post-ED recurrent primary headache. METHODS: This was a randomized, double-blind efficacy trial. We randomized patients to either naproxen 500 mg or sumatriptan 100 mg for headache recurrence after ED discharge. Patients were eligible if they received parenteral therapy for an acute exacerbation of a primary headache in the ED. Patients who met established criteria for migraine without aura were designated a priori as a homogenous subgroup of interest. We followed all patients by telephone 48 hours after ED discharge. The primary endpoint was the between-group difference in change in pain intensity during the 2-hour period after ingestion of either 500 mg naproxen or 100 mg sumatriptan. This difference was measured on a validated 11-point (0 to 10) verbal numeric rating scale (NRS). Satisfaction with the medication and adverse effects were also assessed. Patients who met criteria for migraine without aura were analyzed twice according to a priori design: once as a homogenous subgroup and then again combined with all other primary headaches. RESULTS: Of 410 patients randomized, 383 (93%) had outcome data available for analysis. Two hundred eighty (73%; 95% confidence interval [CI] 68% to 77%) reported headache post-ED discharge and 196 (51%; 95% CI 44% to 58%), including 88 with migraine, took the investigational medication provided to them. The naproxen group improved by a mean of 4.3 NRS points, whereas the sumatriptan group improved by 4.1 points (95% CI for difference of 0.2 points: -0.7 to 1.1 points). Findings were virtually identical among the migraine subset (4.3 versus 4.2 NRS points; 95% CI for difference of 0.1 points: 1.3 to 1.5 points). Seventy-one percent (95% CI 62% to 80%) of naproxen patients and 75% (95% CI 66% to 84%) of sumatriptan patients would want to take the same medication the next time. Adverse effect profiles were also comparable. CONCLUSION: In this trial, nearly three quarters of patients reported headache recurrence within 48 hours of ED discharge. Naproxen 500 mg and sumatriptan 100 mg taken orally relieve post-ED recurrent primary headache and migraine comparably. Clinicians should be guided by medication costs, contraindications, and a patient's previous experience with the medication. PMID- 20303199 TI - Identifying the minimum clinically significant difference in acute pain in the elderly. AB - STUDY OBJECTIVE: To identify the minimum clinically significant difference in pain in elderly emergency department (ED) patients. METHODS: This was an observational, prospective study of a convenience sample of patients aged 65 years or older with acute pain. Patients rated their pain on an 11-point numeric rating scale (NRS) on entering the study and every 30 minutes for 2 hours. The arithmetic minimum clinically significant difference was defined as the mean difference between current and preceding NRS scores when the subject described his or her pain as "a little less pain" or "a little more pain." The proportional minimum clinically significant difference was change in NRS in a 30-minute interval divided by the NRS at the beginning of the interval. We used generalized estimating equations to adjust for nonindependence of pain scores and to test trend over time. RESULTS: One hundred ninety-five patients were enrolled (mean age 74 years; 73% women; 51% Hispanic; 33% black). The arithmetic minimum clinically significant difference averaged over all periods was 1.5 (95% confidence interval 1.3 to 1.6), the proportional minimum clinically significant difference was 25% (95% confidence interval 20% to 29%). The arithmetic minimum clinically significant difference unexpectedly decreased over time: 2.1 from baseline to 30 minutes, 1.4 from 30 to 60 minutes, 1.3 from 60 to 90 minutes, and 1.0 from 90 to 120 minutes (P<.001). In contrast, the proportional differences were more stable: 27% from baseline to 30 minutes, 22% from 30 to 60 minutes, 22% from 60 to 90 minutes, and 28% from 90 to 120 minutes (P=.89). CONCLUSION: The arithmetic minimum clinically significant difference in older ED patients was 1.5 NRS units and decreased over time, whereas the proportional change was 25% and more stable. PMID- 20303200 TI - The recidivism characteristics of an emergency department observation unit. AB - STUDY OBJECTIVE: We describe the recidivism characteristics of an adult emergency department (ED) observation unit population and determine whether rates differ according to demographic or clinical features. METHODS: This prospective observational cohort study of a protocol-driven ED observation unit reviewed all discharged ED observation unit patients who returned within 14 days of discharge for an unscheduled ED visit or direct inpatient admission to the study hospital, or a proximate affiliated hospital, during 6 consecutive months. Age, sex, initial ED observation unit diagnosis, ED observation unit length of stay, and return visit disposition were determined from hospital databases and confirmed by chart review. All return visits were classified as related or unrelated to the index visit. RESULTS: There were 55,727 ED visits, with 4,348 patients admitted to the ED observation unit, of whom 80.7% (3,509) were discharged. Patients with or without a return visit were similar in terms of age (56.9 years [standard deviation (SD) 19.5 years]), percentage of male patients (40.0%), or initial ED observation unit length of stay (15.0 hours [SD 6.0 hours]). Of discharged ED observation unit patients, 375 (10.8%) had a return visit, of which 277 (7.9%) were related. Of return visits, 86.3% of patients had only 1 return visit, 11.6% had 2, and 2.1% had 3 or more; 4.2% of returns occurred at an affiliated hospital. Time to first return visit was clustered within the first week for related visits, with a mean time to return of 4.5 days (SD 3.9 days). On return visit, 40.2% of patients were treated and discharged from the ED, 36.2% were treated in the ED and admitted, 14.4% were treated in the ED and then the ED observation unit and discharged home, 12.3% were directly admitted to the hospital, and 2.5% were treated in the ED and then the ED observation unit and admitted. Among common conditions, related return visit rates were highest for headache (16.1%), back pain (13.8%), and abdominal pain (12.7%) and lowest for chest pain (3.6%). As a group, therapeutic protocols, and specifically painful conditions, had significantly higher related return visit rates than diagnostic protocols (10.8% versus 5.1%). CONCLUSION: Patients who return after an ED observation unit visit are similar to patients who do not return in terms of age, sex, or initial length of stay. However, ED observation unit recidivism rates do differ according to observation category, with painful conditions showing the highest recidivism rates. PMID- 20303201 TI - Impact of Modernising Medical Careers on basic surgical training and experience of oral and maxillofacial higher surgical trainees. AB - Modernising Medical Careers (MMC) is a programme for change that aims to improve the quality of patients' care through improvement in postgraduate medical education and training. Its introduction had far reaching affects and many shortcoming due to its failure to take into account the craft specialties. The aim of this paper is to illustrate the impact of MMC on oral and maxillofacial surgical (OMFS) training. An online questionnaire was distributed to OMFS trainees, and data were gathered about current position, year of training, duration and specialties worked during basic surgical training, stage of completion of examinations and courses, and overall satisfaction with training. Comparisons were made between those who had been trained before and after MMC was introduced. Ninety-five trainees (68%) responded. Of these 66 (69%) had basic surgical training before the introduction of MMC and 29 (31%) afterwards. MMC shortened overall time spent on basic surgical training of OMFS trainees by half, to only 1 year. There were similarities between the two groups in terms of the range of specialties experienced. MMC also resulted in more trainees starting higher surgical training without their Membership of the Royal College of Surgeons. There was greater satisfaction with BST for the pre-MMC group than the post-MMC group. It is hoped that the recent changes to training that were implemented after this study will address some of the shortcomings that we have identified. PMID- 20303203 TI - Do disability pensioners have a higher mortality rate than non-pensioners? Adjusting for potential confounding: a commentary on Hult, Stattin, Janlert and Jarvholm. PMID- 20303204 TI - Resisting blame and managing emotion in general practice: the case of patient suicide. AB - UK Governing bodies are imposing increased forms of regulation on General Practitioners (GPs). This paper explores one example of such governance - the audit of GP practice through Critical Incident Reviews (CIRs) following patient suicide. Drawing on interviews with 16 GPs about their involvement in a CIR of a patient's suicide, we found that the review process initially provoked strong emotions of sadness and guilt as well as fear of blame. Ultimately, however, most GPs felt comforted by the CIRs because their findings confirmed that they were not responsible for the suicide. At the same time, the GPs indicated that such comfort was tenuous due to the broader blame culture and because they foresaw many future audits as part of an inflationary spiral of surveillance and risk management. While the GPs adopted strategies to manage and resist surveillance, the effects of CIRs on patient care may be mixed, with the potential both to improve clinical practice and contribute to adverse outcomes. We argue that CIRs paradoxically contain and create anxieties about suicide among GPs and society more broadly. PMID- 20303205 TI - The impact of subjective and objective social status on psychological distress among men and women in Japan. AB - From around 1990s, social disparity issues and their effects on mental health have been gaining increasing attention in Japanese society. Findings from previous studies on socioeconomic status (SES) and mental health in Japan are inconsistent. Subjective Social Status (SSS) has been proposed and tested as a stronger predictor of mental health than measures such as education, income and occupation in the UK and US, but this has not been tested enough in countries with a different social and cultural background such as Japan. In the present study, a cross-sectional questionnaire survey was conducted in 2006 among a nationally representative community-based random sample of residents in Japan aged 20-74 years. A total of 1237 participants completed the questionnaire, with the overall response rate of 61.9%. After excluding 42 respondents, data from 1195 respondents (574 men and 621 women) were analyzed. SSS, household income, and education level of respondents were measured using single-item questions. Those with a K6 score of 5 or greater were defined as having psychological distress. A multiple logistic regression model was used to examine the effects of SSS, household income, and education on psychological distress. Among men, the prevalence of psychological distress, after adjusting for age and marital status, differed significantly across groups classified based on SSS, household income, and education. Among women, only SSS was significantly associated with psychological distress after adjusting for age and marital status. However, when all three variables were simultaneously entered into the model, SSS and household income were significantly associated with psychological distress, with the low SSS group having a higher odds ratio of psychological distress. In summary, SSS seems to be a stronger predictor of psychological distress among both men and women in the Japanese community than traditional measures of SES. PMID- 20303206 TI - Transverse reduction genioplasty to reduce width of the chin: indications, technique, and results. PMID- 20303207 TI - Oral function after oncological intervention in the oral cavity: a retrospective study. AB - PURPOSE: To assess self-perceived oral function of patients with oral cavity cancer at different stages of treatment, ie, before oncologic intervention, 5 weeks after intervention, and 5 years after intervention. PATIENTS AND METHODS: A cohort of 158 patients with malignancy in the oral cavity treated by surgery in 1999 or 2000 was included. From this cohort we interviewed 69 patients by telephone in 2005 and collected data on dental status, disorders of chewing and swallowing, xerostomia, preference of food consistency, tube nutrition, weight loss, and speech for different stages of treatment. RESULTS: For patients treated in the maxilla region we observed a significant (P < .05) recovery of perceived chewing ability after 5 years to the level experienced before oncologic intervention. Patients treated in the mandible region reported a deteriorated dental state, chewing ability, lip competence, and xerostomia after 5 years. Patients treated in the tongue and mouth-floor region experienced deterioration for dental state, chewing ability, and xerostomia after 5 years compared with the level before the oncologic intervention. CONCLUSIONS: Our telephone interview on oral function provided supplementary information on how patients experienced their problems with oral function during various phases of oncologic treatment. A retrospective interview may thus help to add information to incomplete retrospective data. PMID- 20303208 TI - Management of in-flight medical emergencies. PMID- 20303209 TI - Open versus closed treatment of unilateral subcondylar and condylar neck fractures: a prospective, randomized clinical study. AB - PURPOSE: The purpose of the present study was to compare closed treatment with open reduction and internal fixation for displaced unilateral subcondylar and condylar neck fractures. MATERIALS AND METHODS: A total of 32 patients with displaced unilateral condylar fractures were included in the present study. Of the 32 patients, 27 were men and 5 were women. The patients were divided into 2 groups. The group I patients were treated with closed treatment and rigid maxillomandibular fixation, and group II patients were treated with open reduction and internal fixation. The patients were assessed for maximal interincisal opening, protrusive movements, lateral excursion movements on the fractured and nonfractured sides, anatomic reduction of the condyle on radiography, pain in the temporomandibular joint, and malocclusion. Parameters such as the maximal interincisal opening, protrusive movements, and lateral excursion movements on the fractured and nonfractured sides between the 2 groups were compared statistically using an independent t test. Parameters such as anatomic reduction of the condyle, pain in the temporomandibular joint, and malocclusion between the 2 groups were compared statistically using the chi(2) test. RESULTS: No significant difference was found between the 2 groups in the maximal interincisal opening, protrusion, lateral excursion movement, malocclusion, and temporomandibular joint pain; however, a statistically significant difference was seen in the anatomic reduction of the condyle. CONCLUSIONS: The results of the present study have shown that no significant clinical difference exists between patients undergoing closed treatment and rigid maxillomandibular fixation or open reduction and internal fixation. However, a radiographically better anatomic reduction of the condylar process was seen in the patients treated with open reduction and internal fixation. PMID- 20303210 TI - Prevalence and risk factors for early postpartum anemia. AB - OBJECTIVE: To assess the prevalence and evaluate the most important risk factors for early postpartum anemia. STUDY DESIGN: The perinatal process data of 43,807 women delivering between 1993 and 2008 (90.1% of all deliveries) in the largest university obstetric department in Germany were analyzed, and the associations of Hb<8 g/dl with maternal characteristics, pregnancy risks, delivery mode and estimated delivery blood loss were calculated. Multivariable logistic regression models were applied to compute odds ratios. Additionally, the impact of these risk factors for delivery blood loss was estimated with multivariable linear regression analysis. RESULTS: Twenty-two percent of mothers had Hb<10 g/dl, and 3% had Hb<8 g/dl. The adjusted odds ratios (OR) for Hb<8 g/dl were 4.8 (p=0.001) for placenta previa, 2.9 (p<0.001) for mothers of African origin, 2.7 (p<0.001) for diagnosed anemia in pregnancy, 2.2 (p<0.001) for multiple pregnancy, and 2.1 (p=0.021) for bleeding in late pregnancy. However, the delivery blood loss was the most important risk factor for postpartum anemia. The adjusted OR for an estimated blood loss of 500-1000 ml was 15.3 (p<0.001), and for a loss of >1000 ml was 74.7 (p<0.001). CONCLUSION: The estimated obstetric blood loss is the most important risk factor for severe postpartum anemia, and the volume of blood lost is especially high in cesarean deliveries, which should be considered when electing delivery procedures. Also, measures to boost iron stores in pregnancy should be established. PMID- 20303211 TI - Prevalence of cysts in epithelial ovarian cancer. AB - OBJECTIVE: Ovarian carcinomas mostly appear as large cystic masses. However, the exact prevalence of cysts in epithelial ovarian cancer (EOC) has never been documented as well as the tumor factors that are related to the presence of cysts. Demonstrating the prevalence of cysts in EOC is essential for research focused on predictive and prognostic biomarkers in ovarian cyst fluid. STUDY DESIGN: From 233 patients with primary EOC who underwent surgery, pathological data were collected from pathology reports. Univariate and multivariate logistic regression were used to analyze the relationship between the presence of cysts and other tumor characteristics. RESULTS: Cysts in EOC were present in 83.7% of the patients and were mostly (61%) multilocular. The most common histological subtypes (serous, mucinous, endometrioid, clear cell) contained cysts in more than 85% of the cases. In univariate regression analysis, early FIGO stage, low tumor grade and a large tumor size were significantly associated with the presence of cysts (OR (95% CI)=5.312 (1.81-15.57), 6.906 (2.31-20.66) and 1.169 (1.08-1.27), respectively). In multivariate regression analysis, apart from tumor size, only tumor grade was independently associated with the presence of cysts (adjusted OR (95% CI)=4.234 (1.36-13.22)). CONCLUSIONS: The large majority of all EOCs contained cysts. Histological subtype, FIGO stage, tumor necrosis and age were not associated with the presence of cystic EOC. In contrast, tumor grade and tumor size were independently related to the presence of cystic EOC. This means that cystic EOCs represent a subgroup of larger and more well-differentiated tumors. The evident relationship between the presence of cysts and differentiation grade is interesting from a clinical point of view as grading is especially important for the prognosis and treatment of patients with stage I EOC. PMID- 20303213 TI - Laryngeal plexiform schwannoma as first symptom in a patient with neurofibromatosis type 2. AB - Neurofibromatosis type 2 (NF2) is an autosomal dominant disorder characterized by bilateral vestibular schwannomas. The initial symptoms of NF2 are usually hearing loss and tinnitus caused by vestibular schwannomas. Although other intracranial, spinal, or skin tumors also occur in NF2, laryngeal lesions are very rare. We report a rare case of NF2 with laryngeal plexiform schwannoma as first symptom. A 38-year-old man presented with a smooth-surfaced submucosal supraglottic mass. Two round masses in the left chest wall and left supraclavicular fossa were noted incidentally during investigation of the laryngeal mass. Magnetic resonance imaging (MRI) findings for these masses were identical to those of the laryngeal mass. No typical symptoms related to NF2 were identified. Histologically, the laryngeal tumor represented plexiform schwannoma. We thus considered that the two round masses in the left chest wall and left supraclavicular fossa might also represent plexiform schwannomas. NF2 was suspected, as a high incidence of multiple plexiform schwannomas has been suggested for patients with NF2. MRI of brain lesions demonstrated bilateral vestibular schwannomas and multiple meningiomas. Finally, NF2 with laryngeal plexiform schwannoma was diagnosed. Recognizing that multiple plexiform schwannomas could be associated with NF2 is important. PMID- 20303214 TI - Application of modified nano-alumina as a solid phase extraction sorbent for the preconcentration of Cd and Pb in water and herbal samples prior to flame atomic absorption spectrometry determination. AB - The first study on the high efficiency of nanometer-sized gamma-alumina coated with sodium dodecyl sulfate-1-(2-pyridylazo)-2-naphthol (SDS-PAN) as a new sorbent solid phase extraction (SPE) has been reported. A microcolumn packed with modified nanometer-sized alumina was used to preconcentrate and separate Cd and Pb in water and herbal samples. The metals were eluted with 2 mL HNO(3) directly and detected with the detection system flame atomic absorption spectrometry (FAAS). Various influencing parameters on the separation and preconcentration of trace metals, such as pH, flow rate, sample volume, amount of sorbent, and concentration of eluent, were studied. Under the optimized operating conditions, the sorption capacities of the modified nano-gamma-alumina for Cd and Pb were 11.1 and 16.4 mg g(-1) respectively. With 500.0 mL sample an enrichment factor of 250 was obtained. The detection limits of this method for Cd and Pb were 0.15 and 0.17 microg L(-1) and the R.S.D.s were 2.8 and 3.2% (n=10), respectively. The proposed method has been applied to the determination of these metal ions at trace levels in certified reference materials and real samples with satisfactory results. PMID- 20303215 TI - Three-channel false colour AFM images for improved interpretation of complex surfaces: a study of filamentous cyanobacteria. AB - Imaging signals derived from the atomic force microscope (AFM) are typically presented as separate adjacent images with greyscale or pseudo-colour palettes. We propose that information-rich false-colour composites are a useful means of presenting three-channel AFM image data. This method can aid the interpretation of complex surfaces and facilitate the perception of information that is convoluted across data channels. We illustrate this approach with images of filamentous cyanobacteria imaged in air and under aqueous buffer, using both deflection-modulation (contact) mode and amplitude-modulation (tapping) mode. Topography-dependent contrast in the error and tertiary signals aids the interpretation of the topography signal by contributing additional data, resulting in a more detailed image, and by showing variations in the probe surface interaction. Moreover, topography-independent contrast and topography dependent contrast in the tertiary data image (phase or friction) can be distinguished more easily as a consequence of the three dimensional colour-space. PMID- 20303216 TI - Detection of human serum albumin on protein array using scanning tunneling microscopy. AB - Electrical detection of biological binding events, such as protein-protein interaction and DNA hybridization, has emerged as an alternative method to conventional colorimetric and fluorescence based methods. In this study, we demonstrate an electrical detection technique of protein array which can be simply extended for multifunctional measurements and detection of biological binding events on micro-scale array. Micro-contact technique was used for the fabrication of protein chip. The fabricated protein array on Au substrate was characterized by fluorescence microscopy and scanning tunneling microscopy (STM). The chip was designed to investigate immunocomplexes comprised of our model protein, human serum albumin (HSA), corresponding antibody fragments, and Au nanoparticle-antibody conjugates. The peak-like pulse obtained by electrical tunneling current between these complexes and the STM tip varies on the surface density of the bound complexes. Using the electrical detection technique based on STM, 100fg/mL of HSA could be successfully detected by STM. Importantly, the proposed concept of measurement could allow multiple analyses of analytes at nano scale array, which is difficult to be analyzed by conventional fluorescence based method. PMID- 20303217 TI - The cost-effectiveness of particle therapy in non-small cell lung cancer: exploring decision uncertainty and areas for future research. AB - PURPOSE: To review and synthesize all available evidence in order to explore the cost-effectiveness of particle therapy (carbon-ions, protons) compared to the best current treatments for non-small-cell lung cancer (NSCLC), and the value of additional research. The present study focuses on stage I NSCLC, as no data is available for more advanced stages. METHODS: A probabilistic decision-analytic Markov model was constructed to synthesize all available evidence. Comparative treatments were carbon-ions, protons, conventional radiotherapy (CRT) and stereotactic radiotherapy (SBRT) for inoperable stage I NSCLC; and carbon-ions and SBRT for operable stage I NSCLC. The expected value of perfect information (EVPI) was calculated to support research decisions. RESULTS: For inoperable stage I NSCLC, carbon-ion therapy costed euro 67.257 per quality-adjusted-life year gained compared to SBRT. Both treatments dominated protons and CRT. Considerable uncertainty surrounded these results, resulting in a high EVPI. For operable stage I NSCLC SBRT dominated carbon-ion therapy. CONCLUSIONS: Due to the considerable uncertainty in stage I NSCLC, and the lack of data on more advanced stages, it is recommended not to adopt particle therapy as standard treatment in NSCLC yet. More evidence is needed to reduce the decision uncertainty and to support evidence-based treatment decisions. It might be worthwhile to invest in a particle facility for clinical research. Future research should also weigh the investment risk, value of information and costs of delay. PMID- 20303218 TI - To be, or not to be obese - that's the challenge: a hypothesis on the cortical inhibition of the hypothalamus and its therapeutical consequences. AB - Today, obesity is the most urgent unsolved medical problem, with the threat of a decreased life expectancy rate for the first time in medical history. Many obese subjects try to lose weight by dieting and exercising, without success on a long term basis. The only therapy with some effect is bariatric surgery with the impact of sustainable adverse effects only suitable in morbid obesity. Why are the therapies to treat obesity not working? Within the last years, we have become more aware of the role of the brain in energy homeostasis. The three main players within the brain controlling our weight are the cortex for cognition, hypothalamus for vital body functions and limbic-reward system for emotions. One hypothesizes that the failure of the cortex to inhibit the hypothalamus is the main cause of obesity. The evolutionary old hypothalamus constantly seeks for a positive energy balance, always in endeavor to avoid any energy shortage in the future. The hypothalamus is executing its tasks in a parallel mode. It can coordinate a set of vital routines independently, yet simultaneously. For e.g., energy balance, salt balance, body temperature and sleep are executed even in a coma. The hypothalamus is primitive but stable. The cortex in humans is, compared to rodents, much bigger and more complex, while the hypothalamus bears more similarities between these two species. The cortex in humans is evolutionary younger and represents higher cognition, an unique human feature. In contrast to the hypothalamus, the cortex focuses on one problem at a time, thus functioning on an attention-based manner. Due to this serial mode, the cortex uses a large part of its capacity for one problem at a time. Therefore, it can solve more complex calculations than the hypothalamus by thinking about one problem after another. It is even strong enough to veto the hypothalamus, if necessary. If the concentration on weight loss is distorted, the hypothalamus is free of inhibition by the cortex, and the subject will gain weight again. It is suggested that this is why diets do not work in the long term. In anorexic patients, the cortex is fully occupied to control the hypothalamus resulting in extreme weight loss. In obese subjects, the cortex is less disciplined and the hypothalamus will take control again to stimulate positive energy balance. From this viewpoint, the limbic-reward system interacts both with the hypothalamus and the cortex to achieve demands by emotional motivation. The last part of this paper describes a therapeutic strategy based on this hypothesis. We propose a dual approach to fight obesity. First, interventions should be implemented that remind the cortex to control the hypothalamus and second, to stimulate physiological feedback to the hypothalamus. PMID- 20303219 TI - Lymphangiogenesis may explain adrenal selectivity in lung cancer metastases. AB - The 'seed and soil' hypothesis of organ selectivity in cancer metastasis dated back to the 1870s. A century later, a review of significant selectivity data revealed that the adrenals featured in 11 of 12 classes of it, thus promoting these two organs for research. Fortunately, two discoveries have also occurred, namely, (a) that cancer stimulates lymph vessel formation, i.e., lymphangiogenesis, and (b) that lymph and blood vessels are differentially stainable. Accordingly, these interesting ideas should be exploited with a hypothesis. Therefore, it is proposed that, at autopsy in lung cancer cases, the tissues between the primary lung tumor and the adrenal secondary should be meticulously serially sectioned and disjunctively stained because they must reveal what naturally occurs in this zone during life. It is predicted that this maneuver will identify lymphangiogenesis as the phenomenon responsible for the age-old puzzle of adrenal selectivity. Indeed, it may explain other puzzles such as intracranial lymphatic connectivity. PMID- 20303220 TI - Cerebellar neurocognition and Korsakoff's syndrome: an hypothesis. AB - In literature, the cerebellum is given a substantial role in cognitive processes, in addition to traditional views on cerebellar function of regulating motor behaviour. The phenomenon of cerebellar damage causing impairments in memory and executive functioning was observed in various cerebellar disorders. Cerebellar cognitive dysfunction can be interpreted as a disturbance of cerebello-cerebral connections to areas of the cerebral cortex involved in cognitive processing, but the exact nature of the cognitive dysregulation is not known. Memory and executive dysfunction are important clinical features of Korsakoff's syndrome. We hypothesize that the Korsakoff syndrome might be an example of cerebellar neurocognitive dysfunctioning, caused by cerebello-cerebral pathways being disconnected in brain areas that are classically affected in Wernicke's encephalopathy. Further research is needed to support the possibility of cerebellar neurocognitive disturbances in Korsakoff's syndrome. If correct, this hypothesis may contribute to a better understanding of the clinical and neuropsychological profile of Korsakoff's syndrome. PMID- 20303221 TI - Predictors of crack cocaine initiation among Montreal street youth: a first look at the phenomenon. AB - BACKGROUND: Crack cocaine use is increasing in Montreal. However, initiation risk factors among street youth are unknown. The goal of this project is to estimate the incidence of first crack cocaine use among these youth and to identify the associated risk factors. METHODS: A prospective cohort study of HIV and hepatitis C incidence was conducted among street youth from 2001 to 2005. A questionnaire on sexual and drug use behaviours was administered every 6 months. Incidence was estimated (a) for youth who had never used crack cocaine at recruitment (n=203) and, among them, (b) for those who had snorted cocaine before (n=122). The risk factors for initiation of crack use as well for initiation into a new route of cocaine administration among youth who had snorted cocaine before were determined using Cox regression. RESULTS: Incidence rates for crack cocaine use were (a) 136.6/1000 person-years (p-y) (95% confidence interval [CI]: 104.5-175.5) and (b) 205.8/1000 p-y (95% CI: 150.2-275.3). The number of substance types used recently increased the risk of initiating crack use (adjusted hazard ratio [AHR]=1.84 per substance type, 95% CI: 1.55-2.18), whereas having a parent with a substance abuse problem decreased that risk (AHR=0.48, 95% CI: 0.26-0.89). The risk factors were identical among youth who had snorted cocaine before. CONCLUSIONS: Our analyses show a high incidence of crack use among street youth. It is important to delve more deeply into the phenomenon of initiation if we wish to develop effective prevention measures for these young people. PMID- 20303222 TI - Sexuality and intimacy after gynecological cancer. AB - Matters of sexuality and intimacy greatly impact quality of life of patients with gynecologic cancers. Vast amount of evidence exists showing that cancer dramatically impacts woman's sexuality, sexual functioning, intimate relationships and sense of self. Sexual functioning can be affected by illness, pain, anxiety, anger, stressful circumstances and medications. There is a growing acknowledgement that these needs are not being appropriately addressed by providers. With improvements in early detection, surgery and adjuvant therapy for gynecologic cancer, long term survival and cure are becoming possible. Quality of life is thus becoming a major issue for patients. Patients suffer from hot flashes, difficulty sleeping, loss of libido and intimacy, all resulting in significant morbidity and loss of quality of life. Using hormone replacement therapy in gynecologic cancer survivors is a topic a great debate. While limited studies are available to date, retrospective cohort reviews show no reported differences in overall or disease-free survival in patients using hormone replacements vs. controls in patients with ovarian cancer, endometrial cancer, cervical, vaginal or vulva cancer. Since safety of using HRT remains controversial and prospective studies are lacking, providers need to be able to provide alternatives to HRT. Centrally acting agents such as antiseizure agent gabapentin and selective serotonine re-uptake inhibitors, such as venlafaxine and fluoxitine have been demonstrated to show effectiveness in treating vasomotor symptoms and are easily tolerated. To address cardiovascular and osteoporosis risks of post-menopausal status, exercise, healthy diet, bisphosphonates, raloxifen and statins have been found to be effective. Psychotherapy plays an essential part in management of these issues. Review of the literature reveals recent trends among health psychologists to utilize psychoeducational interventions that include combined elements of cognitive and behavioral therapy with education and mindfulness training. Intervention studies have found positive effects from this approach, particularly within the areas of arousal, orgasm, satisfaction, overall well-being, and decreased depression. Many of patients' issues are easy to address with either hormonal, non-hormonal or psychotherapy modifications. The essential part of success is the providers appreciation of this serous problem and willingness and comfort in addressing it. PMID- 20303223 TI - INTERPOL DVI best-practice standards--An overview. AB - A description of the International Criminal Police Organization and its role in disaster victim identification is provided along with a summary of the standards developed and circulated to responders in INTERPOL member countries (188 throughout the world) to insure evidence-based DVI practices. Following the INTERPOL-mediated DVI response in 2005 to the SE Asia tsunami, many lessons learned have been recorded. Based on these current standards, INTERPOL's approach to DVI reflects a modern approach and philosophy. PMID- 20303224 TI - Sequential neuroradiological and neurophysiological studies in a Japanese girl with merosin-deficient congenital muscular dystrophy. AB - We describe the early manifestation and sequential assessment of the central and peripheral nervous system in a Japanese girl with merosin-deficient congenital muscular dystrophy. She showed severe hypotonia (''floppy infant") and suffered mild respiratory failure postnatally. Serum creatine kinase was elevated to 11,487 IU/L. The muscle biopsy showed dystrophic changes with negative expression of merosin (laminin alpha2), thereby confirming merosin-deficient congenital muscular dystrophy. Her motor milestones were severely delayed, but she could sit without support at the age of 3 years. After 3 years, her motor ability deteriorated and by the age of 5 years, she could not sit and control her neck. Magnetic resonance imaging (MRI) at 2 months of age revealed patterns that were appropriate for her age. At 1 year of age, the T2 weighted images showed diffuse high signal intensities throughout the centrum semiovale, and periventricular and subcortical white matter of the frontal and occipital lobes, while the U fibers, the corpus callosum and the internal capsule were spared. At the age of 7 years, these white matter abnormalities decreased. MR spectroscopy (MRS) revealed normal values of N-acetylaspartate (NAA)/creatine (Cr) and choline (Cho)/Cr metabolite ratios as well as slightly increased myoinositol (mI)/Cr metabolite ratios. Neurophysiological motor nerve conduction velocity (MCV) and compound muscle action potential (CMAP) of the median nerve were in the normal range at the age of 2 months. After the child reached 1 year of age, the MCV and CMAP lagged behind those of healthy controlled children. The sensory nerve conduction velocity of the median nerve demonstrated a mild delay at the age of 15 months. It improved to normal range at the age of 6 years but decreased at 7 years of age. These sequential findings suggest not only that muscular degeneration and dysmyelination had occurred but also that various other factors, including demyelination and the vasogenic system, may influence the pathology of MDC1A. PMID- 20303225 TI - Treatments for pediatric achalasia: Heller myotomy or pneumatic dilatation? AB - AIM: The treatment of achalasia consists of reducing distal esophageal obstruction by either Heller myotomy surgery or endoscopic pneumatic dilatation. The aim of the present study was to evaluate the short- and middle-term results of these procedures in children. METHODOLOGY: For technical reasons, children under six years old (n=8) were treated by surgery only, whereas patients over six years old (n=14) were treated by either Heller myotomy or pneumatic dilatation. RESULTS: Of the children aged under six years, 75% were symptom-free at six months and 83% at 24 months of follow-up. Of the patients aged over six years, complete remission was achieved by Heller myotomy in 44.5% vs. 55.5% by pneumatic dilatation after six months, and in 40% vs. 65%, respectively, after 24 months. Both pneumatic dilatation and Heller myotomy showed significant rates of failure. CONCLUSION: These results suggest that pneumatic dilatation may be considered a primary treatment in children over six years old. Also, where necessary, Heller myotomy and pneumatic dilatation may be used as complementary treatments. PMID- 20303226 TI - Intracranial solitary fibrous tumor: imaging findings. AB - OBJECTIVE: To study the neuroimaging features of intracranial solitary fibrous tumors (ISFTs). MATERIALS AND METHODS: Retrospective study of neuroimaging features of 9 consecutive histopathologically proven ISFT cases. Location, size, shape, density, signal intensity and gadolinium uptake were studied at CT and MRI. Data collected from diffusion-weighted imaging (DWI) (3 patients), perfusion imaging and MR spectroscopy (2 patients), and DSA (4 patients) were also analyzed. RESULTS: The tumors most frequently arose from the intracranial meninges (7/9), while the other lesions were intraventricular. Tumor size ranged from 2.5 to 10 cm (mean=6.6 cm). They presented multilobular shape in 6/9 patients. Most ISFTs were heterogeneous (7/9) with areas of low T2 signal intensity that strongly enhanced after gadolinium administration (6/8). Erosion of the skull was present in about half of the cases (4/9). Components with decreased apparent diffusion coefficient were seen in 2/3 ISFTs on DWI. Spectroscopy revealed elevated peaks of choline and myo-inositol. MR perfusion showed features of hyperperfusion. CONCLUSION: ISFT should be considered in cases of extra-axial, supratentorial, heterogeneous, hypervascular tumor. Areas of low T2 signal intensity that strongly enhance after gadolinium injection are suggestive of this diagnosis. Restricted diffusion and elevated peak of myo inositol may be additional valuable features. PMID- 20303227 TI - Imaging the olfactory tract (cranial nerve #1). AB - This review paper browses pros and cons of the different radiological modalities for imaging the olfactory tract and highlights the potential benefits and limitation of more recent advances in MR and CT technology. A systematic pictorial overview of pathological conditions affecting olfactory sense is given. Techniques for collecting quantitative data on olfactory bulb volume and on olfactory sulcus depth are described. At last, insights into functional imaging of olfactory sense are shown. PMID- 20303228 TI - Fast healthcare: brief communication, traps and opportunities. AB - Resource considerations have meant that brevity in health care interventions is a high priority, and have led to a constant striving after ever more impressive time efficiency. The UK's National Health Service may be described as a kind of 'fast healthcare', where everyone is task busy, time is money, bed spaces are frenetically shuffled so as to accommodate the most needy and there appears to be 'no time to talk'. Indeed, a great many health care encounters are taking place in short 'blips' often of 5min or less across a range of sites and involving a vast number of practitioners. In this paper we explore how brief communication can both alienate and be therapeutic for patients. We theorise brief interactions by considering a number of traditions of work in anthropology, linguistics and sociology and conclude that health care providers need to invest much more in the skills and strategies for how best to communicate briefly if it to retain its core tradition of caring for others. PMID- 20303229 TI - Optimizing patient education for people with obesity: possible use of the autobiographical approach. AB - OBJECTIVE: To review recent results of the current approaches to the education of obese people, focusing on the motivation for healthy behaviors, and to present the narrative-autobiographical approach as a possible tool in the education of obese people. METHODS: Our overview will necessarily be partial, and limited to some studies that succeeded in improving the motivation for healthy lifestyles in people with overweight or obesity. We will also describe the use of the autobiographical approach in the "Io-muovo-la-mia-vita" project. RESULTS: Many studies have induced relevant behavioral changes, mainly by using intensive interventions. Weight loss maintenance has been difficult and usually has required pro-active follow-up interventions. The use of self-writing may allow overweight and obese people to reveal their inner feelings to themselves and to peers, and may reinforce their motivation for self-care. CONCLUSIONS: The association of weight loss with intensive interventions, and the need for follow up pro-active interventions to maintain results make one wonder whether the inner motivation of participants is usually fostered as recommended. PRACTICE IMPLICATIONS: The narrative-autobiographical approach appears to be a proper way to patient centered care, but for an effective practice, the human and relational attitudes of healthcare professionals should be integrated with specific educational skills. PMID- 20303230 TI - A course for nurses to handle difficult communication situations. A randomized controlled trial of impact on self-efficacy and performance. AB - OBJECTIVE: to evaluate the impact of a communication skills course for nurses on how to handle difficult communication situations in their daily work. METHODS: a 7-h course was developed using a construct of "Awareness, Feelings, Listen, Solve" (AFLS). A pedagogy of experiential, learner-centered learning was adopted. The course evaluation used a randomized controlled design with pre- and post measures of self-efficacy and performance. RESULTS: forty-one nurses volunteered and thirty-three nurses completed all assigned parts of the study. On self assessment, there was significant improvement for self-efficacy (F=24.43, p<0.001), but not for emotional awareness. On performance, there was no significant improvement between intervention and control groups (F=3.46, p=0.073). CONCLUSION: a short course for nurses on handling difficult communication situations achieved significant improvements in self-efficacy but not in performance. PRACTICE IMPLICATIONS: teaching communication skills in community-based settings is important for the safety and effectiveness of patient care. Sponsoring organizations should weigh trade-offs between feasibility and achievement of measurable improvements in performance. One possible approach is to focus on specific communication skills rather than a full suite of skills. PMID- 20303231 TI - Treatment of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), a multisystem disease, should target the pathophysiological aberrations (inflammatory and oxidative and nitrosative stress pathways), not the psychosocial "barriers" for a new equilibrium. PMID- 20303232 TI - Barriers and enablers in the implementation of a provider-based intervention to stimulate culturally appropriate hypertension education. AB - OBJECTIVE: to identify barriers and enablers influencing the implementation of an intervention to stimulate culturally appropriate hypertension education (CAHE) among health care providers in primary care. METHODS: the intervention was piloted in three Dutch health centers. It consists of a toolkit for CAHE, training, and feedback meetings for hypertension educators. Data were collected from 16 hypertension educators (nurse practitioners and general practice assistants) during feedback meetings and analyzed using qualitative content analysis. RESULTS: perceived barriers to the implementation of the intervention fell into three main categories: political context (health care system financing); organizational factors (ongoing organizational changes, work environment, time constraints and staffing) and care provider-related factors (routines, attitudes, computer and educational skills, and cultural background). Few barriers were specifically related to the delivery of CAHE (e.g. resistance to registering ethnicity). Enabling strategies addressing these barriers consisted of reorganizing practice procedures, team coordination, and providing reminders and additional instructions to hypertension educators. CONCLUSION AND PRACTICE IMPLICATIONS: the adoption of a tool for CAHE by care providers can be accomplished if barriers are identified and addressed. The majority of these barriers are commonly associated with the implementation of health care innovations in general and do not indicate resistance to providing culturally appropriate care. PMID- 20303234 TI - [Periostitis in systemic necrotizing vasculitides: Study of the 4 cases identified among the 1762 patients of the FVSG database and review of the literature]. AB - BACKGROUND: Periostitis (periosteal new bone formation) is a rare manifestation of systemic necrotizing vasculitis. PATIENTS AND METHODS: We searched the French Vasculitis Study Group (FVSG) database, established in 1980 and containing the data on 1762 patients with a systemic necrotizing vasculitis, i.e., polyarteritis nodosa (PAN), microscopic polyangiitis, Churg-Strauss syndrome or Wegener's granulomatosis, for those with periostitis. Herein, we describe their characteristics and outcomes. RESULTS: Only 4 patients with periostitis were identified. All had limited and localized PAN-like vasculitis, without poor prognosis factors. Periostitis was painful and localized to the lower limbs in all of them and associated with local myositis in 2. Pain and inflammation resolved under corticosteroids in all, but relapses or corticosteroid-dependence ultimately required the adjunction of an immunosuppressant for 3. With a median follow-up of 10 [range: 4-11] years, only 1 developed peripheral neuropathy and none progressed to a more systemic form of vasculitis, i.e., with severe visceral involvement. DISCUSSION AND CONCLUSIONS: Physicians should be aware that periostitis, usually localized, is a potential manifestation of systemic necrotizing vasculitis, especially polyarteritis nodosa. The overall long-term outcome of these patients is good, but relapses or corticosteroid-dependence is frequent. PMID- 20303236 TI - Fat-free milk as a therapeutic approach for constipation and the effect on serum motilin and ghrelin levels. AB - OBJECTIVE: This study explores the effects of fat-free milk supplementation on individuals with chronic constipation with regard to levels of motilin and acylated and des-acylated ghrelin (which affect intestinal motility) and compares them with data from control subjects given whole milk supplementation. METHODS: The investigation was designed according to the constipation severity test of individuals whose ages and body mass indexes were comparable. Individuals with mild constipation (n=10) were supplemented with 400 mL of fat-free milk daily; moderate constipation cases (n=10) were supplemented with 600 mL, and severe constipation cases (n=10) were supplemented with 800 mL of fat-free milk daily. Healthy control subjects were administered 400 mL of fat-free milk (group 1), which was followed a month later by administration of 400 mL of whole milk for 3 days (group 2). Blood samples were collected from the subjects before and after milk supplementation for hormone analyses. Motilin and acylated and des-acylated ghrelin were quantified with ELISA assay. RESULTS: Supplementation of fat-free milk significantly increased levels of circulating motilin and ghrelin in all groups, including the control subjects, but whole milk supplementation led to a decrease in these hormone levels in the control subjects. CONCLUSION: Drinking fat-free milk might be a new way of solving constipation. PMID- 20303237 TI - Early secondary closure of alveolar clefts with mandibular symphyseal bone grafts and beta-tri calcium phosphate (beta-TCP). AB - Alveolar reconstruction of bony defects in cleft lip and palate patients is a widely accepted treatment regimen for which multiple donor sites can be used. For 25 years, autogeneous bicortical mandibular symphyseal bone grafts have been used at the authors' centre. In cases in which the alveolar defect was too large to match the volume of the mandibular symphyseal bone transplant, beta-TCP granules were packed against the bone transplant to fill the defect completely. In a retrospective study, 18 patients, who were treated with mandibular symphyseal bone wrapped in beta-TCP granules, were compared with 29 patients, who were treated with mandibular symphyseal bone only. To assess alveolar height, occlusal radiographs were taken directly postoperatively and 1 year later. Mean alveolar bone loss was calculated and compared between groups using Student's t-test and linear regression analysis. No statistically significant difference in alveolar height was found between the two groups. It was concluded that mandibular symphyseal bone grafts enriched with beta-TCP granules can be used successfully in cases in which the alveolar cleft is too large to be grafted with mandibular symphyseal bone alone. PMID- 20303238 TI - Cystic change in alveolar bone graft. AB - The authors report a cystic lesion within a previous unilateral cleft lip and alveolus bone graft site in a 15-year-old girl, 5 years after the secondary bone graft. The cyst comprised respiratory epithelial lining, which is thought to be a remnant of the nasal mucosal lining of the primary cleft. PMID- 20303239 TI - Syndromic micrognathia and peri-natal management with the ex-utero intra-partum treatment (EXIT) procedure. AB - Many advances in healthcare are built on advances in technology. In the case of fetal medicine, technology has availed an entirely new patient population. The authors report a case of severe micrognathia and Pierre Robin Sequence that was diagnosed prenatally. Antenatal planning and treatment were instituted via the Fetal Diagnosis/Treatment Team to avoid loss of the neonate's airway. An EXIT procedure was utilized to ensure a secure airway. The benefits of team care for these types of deformities are highlighted including the importance of craniomaxillofacial specialists. PMID- 20303240 TI - The impact of a family history of psychosis on age-at-onset and positive and negative symptoms of schizophrenia: a meta-analysis. AB - The results of research on the relation of family history (FH) of psychosis with clinical presentation in schizophrenia have been mixed. To date, there have been no comprehensive reviews that have examined this body of research. The current review quantitatively evaluates research on the relation of FH with two aspects of schizophrenia, age-at-onset and symptom presentation. Studies investigating the influence of a FH on age-at-onset (N=15 studies), age-at-onset and sex (N=12 studies), and/or positive (N=11 studies) and negative symptoms (N=12 studies) in patients with schizophrenia were included in the meta-analyses. Results showed that FH has a small but significant impact on age-at-onset as well as negative symptoms. Of most interest was the finding that sex differences in age-at-onset are not observed in samples with a FH. Furthermore, there was a significant interaction between FH and sex with respect to negative symptoms. The findings of the current review are discussed in light of the diathesis-stress model. Theoretical assumptions and empirical research are reviewed to support the notion that FH influences susceptibility and presentation through similar mechanisms. Implications of the current findings, limitations of the review, and directions for future research are highlighted. PMID- 20303241 TI - Reduced NGF serum levels and abnormal P300 event-related potential in first episode schizophrenia. AB - Nerve growth factor (NGF) plays a crucial role in central nervous system neuron plasticity. Low levels of serum NGF in schizophrenic patients suggest that the neurotrophin contributes to the pathogenesis of the disease. NGF is also thought to alter characteristics of event-related brain potential (ERP) components. The auditory-evoked P300 ERP component, considered an index of brain activity, has reduced amplitude in acute and chronic schizophrenia. This study evaluated the relationship among serum NGF levels, P300 characteristics, and Positive and Negative Symptom Scale (PANSS) scores in first episode, neuroleptic naive schizophrenic patients (N=30) and healthy controls (N=28). Serum NGF was measured by ELISA and P300 elicited using auditory oddball paradigm. Compared to control subjects, schizophrenic patients had significantly reduced serum NGF (p<0.001) and lower P300 amplitudes at Fz (p=0.003). Additionally, there was a positive correlation between serum NGF serum and P300 amplitude at Fz. No correlation was found between serum NGF or P300 characteristics and PANSS scores. These results suggest that the effects of NGF in schizophrenia are related not only to regulation of neurodevelopment, but also to the electrophysiological characteristics of nerve growth factor. PMID- 20303242 TI - Antagonists of retinoic acid and BMP4 affect fetal mouse osteogenesis and odontoblast differentiation. AB - Retinoic acid and bone morphogenetic protein (BMP4) are endogenous factors indispensable for the physiological development of vertebrates. The proximate aim of the present study was to investigate whether the natural compound citral (a retinoic acid synthesis inhibitor) and a monoclonal, anti-BMP4 antibody, administered to pregnant mice affect in the fetuses cranial osteogenesis and odontoblast differentiation. The present investigation was motivated by the fact that, retinoic acid inhibitors and BMP4 neutralizers may frequently contact human tissues (both intentional and unintentional, and/or unconsciously) inducing unanticipated effects. Our ultimate goal is the prevention of side effects and, future clinical implementation of the results. To this end, pregnant, white mice (balb-c Mus musculus) were intra-abdominally injected with either citral or anti BMP4 antibody at the 9th gestational day. Newborns were processed within 5h, postnatal. Results were evaluated (a) macroscopically, (b) stereoscopically, following histochemical double staining of cartilage and osseous tissues and, (c) microscopically after (c(1)) histological staining of paraffin sections, and, (c(2)) immunohistochemical detection of apoptosis. Data indicate that in vivo administration of citral (biomimicking hypovitaminosis A) caused restriction/retardation of cranial chondrogenesis and osteogenesis. Apoptosis was not detected in teeth tissues. In vivo administration of anti-BMP4 antibody resulted in a transitory interference with the normal course of odontoblast differentiation and the production of pre-dentin, whereas, delay in the ossification also included the alveoli. Animals inspected in adulthood displayed a fairly normal phenotype. It is concluded that those two substances, under their concentrations experienced, are quite safe for the public. PMID- 20303243 TI - [Palliative care in the neonatal period]. PMID- 20303244 TI - [Cholelithiasis associated with portal cavernoma in children: 2 case reports]. AB - The association of cholelithiasis and portal cavernoma is rarely described in adult or pediatric patients. We report 2 cases of gallstone associated with portal cavernoma in 2 girls. The first one suffered from Evans syndrome associated with congenital immune deficiency. The portal cavernoma was discovered with gallstone after splenectomy indicated because of high steroid dependence. In the second case, the cavernoma complicated neonatal umbilical catheterism. The gallstone was asymptomatic and discovered on annual ultrasonography. Septicemia, profound thrombocytopenia, and acute anaemia led to rapid death in the first case. However, the progression was favourable under celioscopic treatment in the second one. Our original observations suggest systematically searching for gallstone in children with portal cavernoma. PMID- 20303245 TI - Intelligent visualization and exploration of time-oriented data of multiple patients. AB - OBJECTIVE: Clinicians and medical researchers alike require useful, intuitive, and intelligent tools to process large amounts of time-oriented multiple-patient data from multiple sources. For analyzing the results of clinical trials or for quality assessment purposes, an aggregated view of a group of patients is often required. To meet this need, we designed and developed the VISualizatIon of Time Oriented RecordS (VISITORS) system, which combines intelligent temporal analysis and information visualization techniques. The VISITORS system includes tools for intelligent retrieval, visualization, exploration, and analysis of raw time oriented data and derived (abstracted) concepts for multiple patient records. To derive meaningful interpretations from raw time-oriented data (known as temporal abstractions), we used the knowledge-based temporal-abstraction method. METHODS: The main module of the VISITORS system is an interactive, ontology-based exploration module, which enables the user to visualize raw data and abstract (derived) concepts for multiple patient records, at several levels of temporal granularity; to explore these concepts; and to display associations among raw and abstract concepts. A knowledge-based delegate function is used to convert multiple data points into one delegate value representing each temporal granule. To select the population of patients to explore, the VISITORS system includes an ontology-based temporal-aggregation specification language and a graphical expression-specification module. The expressions, applied by an external temporal mediator, retrieve a list of patients, a list of relevant time intervals, and a list of time-oriented patients' data sets, by using an expressive set of time and value constraints. RESULTS: Functionality and usability evaluation of the interactive exploration module was performed on a database of more than 1000 oncology patients by a group of 10 users-five clinicians and five medical informaticians. Both types of users were able in a short time (mean of 2.5+/ 0.2min per question) to answer a set of clinical questions, including questions that require the use of specialized operators for finding associations among derived temporal abstractions, with high accuracy (mean of 98.7+/-2.4 on a predefined scale from 0 to 100). There were no significant differences between the response times and between accuracy levels of the exploration of the data using different time lines, i.e., absolute (i.e., calendrical) versus relative (referring to some clinical key event). A system usability scale (SUS) questionnaire filled out by the users demonstrated the VISITORS system to be usable (mean score for the overall group: 69.3), but the clinicians' usability assessment was significantly lower than that of the medical informaticians. CONCLUSIONS: We conclude that intelligent visualization and exploration of longitudinal data of multiple patients with the VISITORS system is feasible, functional, and usable. PMID- 20303246 TI - Practical aspects of implementation of helical tomotherapy for intensity modulated and image-guided radiotherapy. AB - AIMS: Image-guided radiotherapy (IGRT) and intensity-modulated radiotherapy (IMRT) represent two important technical developments that will probably improve patient outcome. Helical tomotherapy, provided by the TomoTherapy HiArt system, provides an elegant integrated solution providing both technologies, although others are available. Here we report our experience of clinical implementation of daily online IGRT and IMRT using helical tomotherapy. MATERIALS AND METHODS: Methods were needed to select patients who would probably benefit. Machine specific commissioning, a quality assurance programme and patient-specific delivery quality assurance were also needed. The planning target volume dose was prescribed as the median dose, with the added criterion that the 95% isodose should cover 99% of the target volume. Although back-up plans, for delivery on conventional linear accelerators, were initially prepared, this practice was abandoned because they were used very rarely. RESULTS: In the first 12 months, 114 patients were accepted for treatment, and 3343 fractions delivered. New starts averaged 2.6 per week, with an average of 17.5 fractions treated per day, and the total number capped at 22. This has subsequently been raised to 24. Of the first 100 patients, 96 were treated with radical intent. Five were considered to have been untreatable on our standard equipment. IGRT is radiographer led and all patients were imaged daily, with positional correction made before treatment, using an action level of 1mm. A formal training programme was developed and implemented before installation. The in-room time fell significantly during the year, reflecting increasing experience and a software upgrade. More recently, after a couch upgrade in April 2009, the mean in-room time fell to 18.6 min. CONCLUSIONS: Successful implementation of tomotherapy was the result of careful planning and effective teamwork. Treatment, including daily image guidance, positional correction and intensity-modulated delivery, is fast and efficient, and can be integrated into routine service. This should encourage the adoption of these technologies. PMID- 20303247 TI - Combining tiotropium and salmeterol in COPD: Effects on airflow obstruction and symptoms. AB - BACKGROUND: Clinical information on 24-h spirometric efficacy of combining tiotropium and salmeterol compared to single-agent therapy is lacking in patients with COPD. METHODS: A randomized, double-blind, four-way crossover study of 6 week treatment periods comparing combination therapy of tiotropium 18 microg plus qd or bid salmeterol 50 microg versus single-agent therapy. Serial 24-h spirometry (FEV(1), FVC), effects on dyspnea (TDI focal score) and rescue salbutamol use were evaluated in 95 patients. RESULTS: Tiotropium plus qd salmeterol was superior to tiotropium or salmeterol alone in average FEV(1) (0 24h) by 72 mL and 97 mL (p<0.0001), respectively. Compared to this qd regimen, combination therapy including bid salmeterol provided comparable daytime (0-12h: 12 mL, p=0.38) bronchodilator effects, but significantly more bronchodilation during the night-time (12-24h: 73 mL, p<0.0001). Clinically relevant improvements in TDI focal score were achieved with bronchodilator combinations including salmeterol qd or bid (2.56 and 2.71; p<0.005 versus components). Symptom benefit of combination therapies was also reflected in less need for reliever medication. All treatments were well tolerated. CONCLUSION: Compared to single-agent therapy, combination therapy of tiotropium plus salmeterol in COPD provided clinically meaningful improvements in airflow obstruction and dyspnea as well as a reduction in reliever medication. PMID- 20303248 TI - Cardiovascular risk factors in men and women with obstructive sleep apnoea syndrome. AB - We wished to evaluate the prevalence of cardiovascular (CV) risk factors in patients with obstructive sleep apnoea syndrome (OSAS) before initiation of continuous positive airway pressure (CPAP), and without any declared or diagnosed pre-existing CV disorder. We wanted to compare the prevalence of these CV risk factors between men and women in an observational study. A questionnaire concerning CV risk factors was submitted to the patients, by a respiratory home care technician at the time of installation of the CPAP treatment. PATIENTS: The study population consisted of 1117 patients; 834 men, 283 women. RESULTS: The prevalence of arterial hypertension (HT), diabetes, obesity, active smoking, hyperlipidemia and family history of coronary heart disease was 54.1%, 22.8%, 65.8%, 18.3%, 33.8% and 20%, respectively. Women had significantly more HT (62.1 vs 51.4%), diabetes (29.9 vs 20.4%), obesity (77 vs 62%) and family history of coronary disease (25.1 vs 18.2%). The prevalence of active smoking was significantly higher in men (20.4 vs 12%). The prevalence of hyperlipidemia was not different between men and women (34.5 vs 31.8%). Stepwise logistic regression showed that HT and diabetes were both independently associated with BMI and age, while diabetes and not HT was independently associated with female gender. The prevalence of classical CV risk factors was very high in this population with OSAS requiring CPAP, especially in women. There is thus a very elevated CV risk level independent of that directly related to OSAS. It is important to screen for and treat classical CV risk factors in this population. PMID- 20303249 TI - Actin-related proteins in the nucleus: life beyond chromatin remodelers. AB - Since their discovery in the mid-1990s, nuclear actin-related proteins (ARPs) have gained attention for their roles as structural components of ATP-dependent chromatin-remodeling complexes. These remodelers can move nucleosomes along the DNA, evict them from chromatin, and exchange histone variants to alter chromatin states locally. Chromatin-remodeling facilitates DNA-templated processes such as transcription regulation, DNA replication, and repair. Consistent with a role for ARPs in shaping chromatin structure, recent genetic studies show that they affect developmental and cell-type specific transcriptional programming. Here, we focus on recent results that suggest a specific contribution of ARPs to long-range interactions in the nucleus, and review evidence indicating that some ARPs may act independently of chromatin-remodeling machines. PMID- 20303250 TI - Abiotic hydrogen production in fresh and altered MSWI-residues: texture and microstructure investigation. AB - Long-term hydrogen generation was observed in a Bavarian mono-landfill for municipal solid waste incineration (MSWI) residues. Hydration reactions of non noble metals, especially aluminum, predominantly produce hydrogen at alkaline reaction conditions. Microscopic investigations show that aluminum metal may occur in different forms: as larger single grains, as small particles embedded in a vitrified matrix or less frequently in blowholes together with metallic silica. Four types of corrosion texture were observed, indicating different reaction mechanisms: aluminum hydroxide rims caused by hydration reactions at alkaline reaction conditions (reaction type 1) and multiphase rims with ettringite and hydrocalumite due to the reaction of aluminum hydroxide with sulfate and chloride ions which are solved in the pore water (reaction type 2). Galvanic corrosion textures due to the electric potential difference between aluminum and embedded intermetallic Fe- or Cu-rich exsolution phases lead to two further corrosion textures: Strong hydration effects of aluminum except a border of aluminum remnant directly beside the Fe- or Cu-rich segregations were only observed in fresh samples (reaction type 3). The reaction type 4 shows a network of Al hydroxide veins occurring along the embedded intermetallic Fe- or Cu-rich exsolution segregation pattern within the metallic aluminum grain. Metal particles enclosed in vitrified particles offers the potential for future corrosion processes. The occurrence of corrosion types 1, 2 and 3 in fresh bottom ashes indicates that these reaction mechanisms predominate during the first reaction period in the presence of chlorine in an alkaline solution. Corrosion type 4, however, was additionally observed in aged samples. Here aluminum acts as sacrificed anode implying electrochemical reaction due to electrolytic pore water. Chloride in the system keeps the reaction alive as Al-hydroxide is solved which normally builds a protection shield around the aluminum metal particles. Due to field observations and experimental results we have reasonable indications that after an initial strong formation of hydrogen the reaction time for hydrogen production in the landfill is lengthened for several decades by the presence of chloride in the alkaline pore water. PMID- 20303251 TI - Changes in enzymatic activities and microbial properties in vermicompost of water hyacinth as affected by pre-composting and fungal inoculation: a comparative study of ergosterol and chitin for estimating fungal biomass. AB - In this experiment, three different fungal species, viz. Trichoderma viridae, Aspergillus niger and Phanerochaete chrysosporium, were inoculated in 7 day and 15 day partially decomposed water hyacinth to study their effect on enzymatic activities, microbial respiration and fungal biomass of the final stabilized product. The results suggested that increasing the duration of pre-composting from 7 days to 15 days did not show any significant effect on the activities of hydrolytic enzymes. Inoculation of fungi significantly (P < or = 0.05) increased cellulase, protease and acid and alkaline phosphatase activities. The highest value of ergosterol was recorded in A. niger-inoculated vermicomposts. Inoculation of P. chrysosporium in initial organic waste registered the highest chitin content in vermicompost. A comparison of fungal biomass and chitin content revealed a conversion factor of 2.628 with a standard deviation of 0.318. Due to significant correlation (r = 0.864), this conversion factor allows for the calculation of fungal biomass from chitin, which is comparatively more stable than ergosterol. PMID- 20303252 TI - Exploitation of olive mill wastewater and liquid cow manure for biogas production. AB - Co-digestion of organic waste streams is an innovative technology for the reduction of methane/greenhouse gas emissions. Different organic substrates are combined to generate a homogeneous mixture as input to the anaerobic reactor in order to increase process performance, realize a more efficient use of equipment and cost-sharing by processing multiple waste streams in a single facility. In this study, the potential of anaerobic digestion for the treatment of a mixture containing olive mill wastewater (OMW) and liquid cow manure (LCM) using a two stage process has been evaluated by using two continuously stirred tank reactors (CSTRs) under mesophilic conditions (35 degrees C) in order to separately monitor and control the processes of acidogenesis and methanogenesis. The overall process was studied with a hydraulic retention time (HRT) of 19 days. The digester was continuously fed with an influent composed (v/v) of 20% OMW and 80% LCM. The average removal of dissolved and total COD was 63.2% and 50%, respectively. The volatile solids (VS) removal was 34.2% for the examined mixture of feedstocks operating the system at an overall OLR of 3.63 g CODL(reactor)(-1)d(-1). Methane production rate at the steady state reached 0.91 L CH(4)L(reactor)(-1)d(-1) or 250.9L CH(4) at standard temperature and pressure conditions (STP) per kg COD fed to the system. PMID- 20303253 TI - Functionalised ZnO-nanorod-based selective electrochemical sensor for intracellular glucose. AB - In this article, we report a functionalised ZnO-nanorod-based selective electrochemical sensor for intracellular glucose. To adjust the sensor for intracellular glucose measurements, we grew hexagonal ZnO nanorods on the tip of a silver-covered borosilicate glass capillary (0.7 microm diameter) and coated them with the enzyme glucose oxidase. The enzyme-coated ZnO nanorods exhibited a glucose-dependent electrochemical potential difference versus an Ag/AgCl reference microelectrode. The potential difference was linear over the concentration range of interest (0.5-1000 microM). The measured glucose concentration in human adipocytes or frog oocytes using our ZnO-nanorod sensor was consistent with values of glucose concentration reported in the literature; furthermore, the sensor was able to show that insulin increased the intracellular glucose concentration. This nanoelectrode device demonstrates a simple technique to measure intracellular glucose concentration. PMID- 20303254 TI - Prefrontal control of fear: more than just extinction. AB - Although fear research has largely focused on the amygdala, recent findings highlight cortical control of the amygdala in the service of fear regulation. In rodent models, it is becoming well established that the infralimbic (IL) prefrontal cortex plays a key role in extinction learning, and recent findings are uncovering molecular mechanisms involved in extinction-related plasticity. Furthermore, mounting evidence implicates the prelimbic (PL) prefrontal cortex in the production of fear responses. Both IL and PL integrate inputs from the amygdala, as well as other structures to gate the expression of fear via projections to inhibitory or excitatory circuits within the amygdala. We suggest that dual control of the amygdala by separate prefrontal modules increases the flexibility of an organism's response to danger cues. PMID- 20303255 TI - Synchronous neural activity and memory formation. AB - Accumulating evidence suggests that the synchronization of neuronal activity plays an important role in memory formation. In particular, several recent studies have demonstrated that enhanced synchronous activity within and among medial temporal lobe structures is correlated with increased memory performance in humans and animals. Modulations in rhythmic synchronization in the gamma frequency (30-100 Hz) and theta-frequency (4-8 Hz) bands have been related to memory performance, and interesting relationships have been described between these oscillations that suggest a mechanism for inter-areal coupling. Neuronal synchronization has also been linked to spike timing-dependent plasticity, a cellular mechanism thought to underlie learning and memory. The available evidence suggests that neuronal synchronization modulates memory performance as well as potential cellular mechanisms of memory storage. PMID- 20303256 TI - Top-down control of visual attention. AB - Top-down visual attention improves perception of selected stimuli and that improvement is reflected in the neural activity at many stages throughout the visual system. Recent studies of top-down attention have elaborated on the signatures of its effects within visual cortex and have begun identifying its causal basis. Evidence from these studies suggests that the correlates of spatial attention exhibited by neurons within the visual system originate from a distributed network of structures involved in the programming of saccadic eye movements. We summarize this evidence and discuss its relationship to the neural mechanisms of spatial working memory. PMID- 20303257 TI - Translational research in brain metastasis is identifying molecular pathways that may lead to the development of new therapeutic strategies. AB - Central nervous system (CNS) or brain metastasis is an emerging area of interest in organ-specific metastasis research. Lung and breast cancers are the most common types of primary tumors to develop brain metastases. This disease complication contributes significantly to the morbidity and mortality of both of these common cancers; as such, brain metastasis is designated an unmet medical need by the US Food and Drug Administration (FDA). Recently, an increase in incidence of CNS disease has been noted in the literature for breast cancer, while it has been an ongoing major complication from lung cancer. Progress in treating brain metastases has been hampered by a lack of model systems, a lack of human tissue samples, and the exclusion of brain metastatic patients from many clinical trials. While each of those is significant, the major impediment to effectively treating brain metastatic disease is the blood-brain barrier (BBB). This barrier excludes most chemotherapeutics from the brain and creates a sanctuary site for metastatic tumors. Recent findings on the biology of this disease and translational leads identified by molecular studies are discussed in this article. PMID- 20303258 TI - The KISS1 metastasis suppressor: a good night kiss for disseminated cancer cells. AB - Re-expression of KISS1 in tumor cell lines allows all antecedent steps of metastasis, but prevents colonization of secondary sites. Because tumor cells have already disseminated by the time of cancer diagnosis, KISS1 may represent a new opportunity for therapeutic intervention. Moreover, numerous clinical reports demonstrate that a loss or reduction of KISS1 expression in different human cancers inversely correlates with tumor progression, metastasis, and survival. Taken together, these observations compel the hypothesis that KISS1 could be of tremendous utility in controlling metastasis in a therapeutic context. In this review, we highlight some key findings from preclinical and clinical studies and discuss strategies whereby KISS1 may be exploited clinically to treat metastases. PMID- 20303259 TI - Cancer stemness and metastasis: therapeutic consequences and perspectives. AB - The transient and dynamic nature of cancer cells that underlie metastasis cannot only be explained by the progressive accumulation of irreversible genetic changes occurring in the primary tumour. The capacity of cells to switch between different cellular identities, as in epithelial to mesenchymal (EMT) and mesenchymal to epithelial transitions (MET), allows them to respond to different cellular environments, thus efficiently disseminating from the primary mass to eventually colonise distant organs. These more dynamic stem-like cancer cells are earmarked by the ability to self-renew and de-/re-differentiate, and eventually recapitulate the heterogeneous composition of the primary tumour in a distant organ site. This dynamic concept of metastasis has profound consequences and implications for cancer diagnostics, prognostics and therapy. Many of the characteristics that define stem cells, like dormancy, active DNA repair, the expression of several drug transporters, and resistance to apoptosis may underlie the capacity of migrating cancer cells to survive conventional therapeutic protocols based on genotoxic agents targeting active proliferating cells. Accordingly, signal transduction pathways that regulate the balance between self renewal and differentiation are likely to represent future targets in the development of tailor-made intervention strategies. Also, specific stem cell features, such as the capacity to migrate to diseased areas (pathotropism), open novel avenues towards the development of cell vehicles capable of tracking and delivering anti-cancer compounds to disseminated metastatic lesions. PMID- 20303260 TI - A novel microtubule-modulating agent induces mitochondrially driven caspase dependent apoptosis via mitotic checkpoint activation in human prostate cancer cells. AB - Hormone-refractory prostate cancer, its skeletal metastasis and complications remain a therapeutic challenge. Here we show that treatment with (S)-3-((R)-9 bromo-4-methoxy-6-methyl-5,6,7,8-tetrahydro-[1,3]dioxolo[4,5-g]isoquinolin-5-yl) 6,7-dimethoxyiso-benzofuran-1(3H)-one (EM011), the brominated analogue of a plant derived non-toxic antitussive alkaloid, noscapine, achieved significant inhibition of hormone-refractory human prostate cancer implanted intratibially in the bone as shown by non-invasive, real-time bioluminescent imaging of tumour growth in nude mice. Mechanistically, in vitro data suggested that the antiproliferative and proapoptotic effects of EM011 in human prostate cancer cell lines were through blockade of cell-cycle progression by impairing the formation of a bipolar spindle apparatus. The G2/M arrest was accompanied by activation of the mitotic checkpoint, a pre-requisite for induction of optimal apoptosis. Attenuation of mitotic checkpoint by siRNA duplexes led to a reduction in mitotic arrest and subsequent apoptosis. Our results further demonstrated participation of an intrinsic mitochondrially mediated apoptotic pathway that ultimately triggered caspase-driven EM011-induced apoptosis. EM011 did not exert any detectable toxicity in normal tissues with frequently dividing cells such as the gut and bone marrow. Thus, these data warrant further evaluation of EM011 for the management of prostate cancer. PMID- 20303262 TI - Optimization of volatile fatty acid production with co-substrate of food wastes and dewatered excess sludge using response surface methodology. AB - Central-composite design (CCD) and response surface methodology (RSM) were used to optimize the parameters of volatile fatty acid (VFA) production from food wastes and dewatered excess sludge in a semi-continuous process. The effects of four variables (food wastes composition in the co-substrate of food wastes and excess sludge, hydraulic retention time (HRT), organic loading rate (OLR), and pH) on acidogenesis were evaluated individually and interactively. The optimum condition derived via RSM was food wastes composition, 88.03%; HRT, 8.92 days; OLR, 8.31 g VSS/ld; and pH 6.99. The experimental VFA concentration was 29,099 mg/l under this optimum condition, which was well in agreement with the predicted value of 28,000 mg/l. PMID- 20303261 TI - Experimental treatment of oestrogen receptor (ER) positive breast cancer with tamoxifen and brivanib alaninate, a VEGFR-2/FGFR-1 kinase inhibitor: a potential clinical application of angiogenesis inhibitors. AB - PURPOSE: Tamoxifen, a selective oestrogen receptor modulator (SERM), and brivanib alaninate, a vascular endothelial growth factor receptor 2 (VEGFR-2) inhibitor, are two target specific agents that result in a substantial decrease in tumour growth when given alone. Tamoxifen activates SERM stimulated breast and endometrial tumour growth. Tamoxifen and brivanib alaninate have side-effects that can affect therapeutic outcomes. The primary goal of the current study was to evaluate the therapeutic effects of lower doses of both agents when given in combination to mice with SERM sensitive, oestrogen stimulated tumour xenografts (MCF-7 E2 tumours). Experiments were conducted to evaluate the response of SERM stimulated breast (MCF-7 Tam, MCF-7 Ral) and endometrial tumours (EnCa 101) to demonstrate the activity of brivanib alaninate in SERM resistant models. EXPERIMENTAL DESIGN: In the current study, tumour xenografts were minced and bi transplanted into the mammary fat pads of athymic, ovariectomised mice. Preliminary experiments were conducted to determine an effective oral dose of tamoxifen and brivanib alaninate that had minimal effect on tumour growth. Doses of 125 microg of tamoxifen and 0.05 mg/g of brivanib alaninate were evaluated. An experiment was designed to evaluate the effect of the two agents together when started at the time of tumour implantation. An additional experiment was done in which tumours were already established and then treated, to obtain enough tumour tissue for molecular analysis. RESULTS: Brivanib alaninate was effective at inhibiting tumour growth in SERM sensitive (MCF-7 E2) and SERM stimulated (EnCa 101, MCF-7 Ral, MCF-7 Tam) models. The effect of the low dose drug combination as an anti-tumour strategy for SERM sensitive (MCF-7 E2) in early treatment was as effective as higher doses of either drug used alone. In established tumours, the combination is successful at decreasing tumour growth, while neither agent alone is effective. Molecular analysis revealed a decreased phosphorylation of VEGFR-2 in tumours that were treated with brivanib alaninate and an increase in VEGFA transcription to compensate for the blockade of VEGFR-2 by increasing the transcription of VEGFA. Tamoxifen increases the phosphorylation of VEGFR-2 and this effect is abrogated by brivanib alaninate. There was also increased necrosis in tumours treated with brivanib alaninate. CONCLUSION: Historically, tamoxifen has a role in blocking angiogenesis as well as the blockade of the ER. Tamoxifen and a low dose of an angiogenesis inhibitor, brivanib alaninate, can potentially be combined not only to maximise therapeutic efficacy but also to retard SERM resistant tumour growth. PMID- 20303263 TI - Novel benzofuran-3-one indole inhibitors of PI3 kinase-alpha and the mammalian target of rapamycin: hit to lead studies. AB - A series of benzofuran-3-one indole phosphatidylinositol-3-kinases (PI3K) inhibitors identified via HTS has been prepared. The optimized inhibitors possess single digit nanomolar activity against p110alpha (PI3K-alpha), good pharmaceutical properties, selectivity versus p110gamma (PI3K-gamma), and tunable selectivity versus the mammalian target of rapamycin (mTOR). Modeling of compounds 9 and 32 in homology models of PI3K-alpha and mTOR supports the proposed rationale for selectivity. Compounds show activity in multiple cellular proliferation assays with signaling through the PI3K pathway confirmed via phospho-Akt inhibition in PC-3 cells. PMID- 20303264 TI - Heterocyclic fused pyridone carboxylic acid M(1) positive allosteric modulators. AB - The phenyl ring in a series of quinolone carboxylic acid M(1) positive allosteric modulators was replaced with a variety of heterocycles in order to reduce protein plasma binding and enhance CNS exposure. PMID- 20303266 TI - Theta-coupled periodic replay in working memory. AB - Working memory allows information from transient events to persist as active neural representations that can be used for goal-directed behaviors such as decision making and learning. Computational modeling based on neuronal firing patterns in animals suggests that one putative mechanism enabling working memory is periodic reactivation (henceforth termed "replay") of the maintained information coordinated by neural oscillations at theta (4-8 Hz) and gamma (30-80 Hz) frequency. To investigate this possibility, we trained multivariate pattern classifier decoding algorithms on oscillatory brain responses to images depicting natural scenes, recorded with high temporal resolution via magnetoencephalography. These classifiers were applied to brain activity recorded during the subsequent five second maintenance of the scenes. This decoding revealed replay during the entire maintenance interval. Replay was specific to whether an indoor or an outdoor scene was maintained and whether maintenance centered on configural associations of scene elements or just single scene elements. Replay was coordinated by the phase of theta and the amount of theta coordination was correlated with working memory performance. By confirming the predictions of a mechanistic model and linking these to behavioral performance in humans, these findings identify theta-coupled replay as a mechanism of working memory maintenance. PMID- 20303267 TI - Human-monkey gaze correlations reveal convergent and divergent patterns of movie viewing. AB - The neuroanatomical organization of the visual system is largely similar across primate species, predicting similar visual behaviors and perceptions. Although responses to trial-by-trial presentation of static images suggest that primates share visual orienting strategies, these reduced stimuli fail to capture key elements of the naturalistic, dynamic visual world in which we evolved. Here, we compared the gaze behavior of humans and macaques when they viewed three different 3-minute movie clips. We found significant intersubject and interspecies gaze correlations, suggesting that both species attend a common set of events in each scene. Comparing human and monkey gaze behavior with a computational saliency model revealed that interspecies gaze correlations were driven by biologically relevant social stimuli overlooked by low-level saliency models. Additionally, humans, but not monkeys, tended to gaze toward the targets of viewed individual's actions or gaze. Together, these data suggest that human and monkey gaze behavior comprises converging and diverging informational strategies, driven by both scene content and context; they are not fully described by simple low-level visual models. PMID- 20303268 TI - Membrane targeting of Bazooka/PAR-3 is mediated by direct binding to phosphoinositide lipids. AB - Cell polarity in higher animals is controlled by evolutionarily conserved protein complexes, which localize to the cytocortex in a polarized manner. The PAR-3/PAR 6/atypical protein kinase C (aPKC) complex is the first to become asymmetrically localized, and it controls the localization of additional complexes functioning further downstream in the regulation of cell polarity. The first component of the PAR-3/PAR-6/aPKC complex that is localized to the cortex is Bazooka/PAR-3 (Baz), a large scaffolding protein. In most cell types analyzed, loss of Baz function leads to loss of cell polarity. Here we present a structure-function analysis of Baz focusing on its subcellular localization and function in four different polarized Drosophila cell types: the embryonic ectodermal epidermis, the follicular epithelium, embryonic neuroblasts, and the oocyte. We show that the PDZ domains of Baz are dispensable for its correct localization, whereas a conserved region in the C-terminal part of Baz to which no function had been assigned so far is required and sufficient for membrane localization. This region binds to phosphoinositide membrane lipids and thus mediates cortical localization of Baz by direct interaction with the plasma membrane. Our findings reveal a mechanism for the coupling of plasma membrane polarity and cortical polarity. PMID- 20303269 TI - Ajuba LIM proteins are negative regulators of the Hippo signaling pathway. AB - The mammalian Ajuba LIM proteins (Ajuba, LIMD1, and WTIP) are adaptor proteins that exhibit the potential to communicate cell adhesive events with nuclear responses to remodel epithelia. Determining their role in vivo, however, has been challenging due to overlapping tissue expression and functional redundancy. Thus, we turned to Drosophila, where a single gene, CG11063 or djub, exists. Drosophila lacking the djub gene or depleted of dJub by RNA interference identify djub as an essential gene for development and a novel regulator of epithelial organ size as a component of the conserved Hippo (Hpo) pathway, which has been implicated in both tissue size control and cancer development. djub-deficient tissues were small and had decreased cell numbers as a result of increased apoptosis and decreased proliferation, due to downregulation of DIAP1 and cyclin E. This phenocopies tissues deficient for Yorkie (Yki), the downstream target of the Hippo pathway. djub genetically interacts with the Hippo pathway, and epistasis suggests that djub lies downstream of hpo. In mammalian and Drosophila cells, Ajuba LIM proteins/dJub interact with LATS/Warts (Wts) and WW45/Sav to inhibit phosphorylation of YAP/Yki. This work describes a novel role for the Ajuba LIM proteins as negative regulators of the Hippo signaling pathway. PMID- 20303265 TI - The role of recently derived FT paralogs in sunflower domestication. AB - Gene duplication provides an important source of genetic raw material for phenotypic diversification, but few studies have detailed the mechanisms through which duplications produce evolutionary novelty within species. Here, we investigate how a set of recently duplicated homologs of the floral inducer FLOWERING LOCUS T (FT) has contributed to sunflower domestication. We find that changes in expression of these duplicates are associated with differences in flowering behavior between wild and domesticated sunflower. In addition, we present genetic and functional evidence demonstrating that a frameshift mutation in one paralog, Helianthus annuus FT 1 (HaFT1), underlies a major QTL for flowering time and experienced a selective sweep during early domestication. Notably, this dominant-negative allele delays flowering through interference with action of another paralog, HaFT4. Together, these data reveal that changes affecting the expression, sequence, and gene interactions of HaFT paralogs have played key roles during sunflower domestication. Our findings also illustrate the important role that evolving interactions between new gene family members may play in fostering phenotypic change. PMID- 20303270 TI - Sensor fusion in identified visual interneurons. AB - Animal locomotion often depends upon stabilization reflexes that use sensory feedback to maintain trajectories and orientation. Such stabilizing reflexes are critically important for the blowfly, whose aerodynamic instability permits outstanding maneuverability but increases the demands placed on flight control. Flies use several sensory systems to drive reflex responses, and recent studies have provided access to the circuitry responsible for combining and employing these sensory inputs. We report that lobula plate VS neurons combine inputs from two optical sensors, the ocelli and the compound eyes. Both systems deliver essential information on in-flight rotations, but our neuronal recordings reveal that the ocelli encode this information in three axes, whereas the compound eyes encode in nine. The difference in dimensionality is reconciled by tuning each VS neuron to the ocellar axis closest to its compound eye axis. We suggest that this simple projection combines the speed of the ocelli with the accuracy of the compound eyes without compromising either. Our findings also support the suggestion that the coordinates of sensory information processing are aligned with axes controlling the natural modes of the fly's flight to improve the efficiency with which sensory signals are transformed into appropriate motor commands. PMID- 20303272 TI - A new formulation of the coefficient of multiple correlation to assess the similarity of waveforms measured synchronously by different motion analysis protocols. AB - Different 3D motion analysis protocols are currently available, but little is known regarding the level of similarity of their outcomes, e.g. whether a joint angle waveform from one protocol can be interchanged with that measured by another protocol. Similarity assessments are therefore urgent to ease the comparison of results. In this context, a major issue is how to quantify the similarity between waveforms measured synchronously through different protocols, within each of many movement-cycles (e.g. gait-cycle), when the effect of protocols on waveforms similarity is the only of interest. For this purpose we developed a new formulation of the statistical index called coefficient of multiple correlation (CMC). The CMC measures the overall similarity of waveforms taking into account the concurrent effects of differences in offset, correlation, and gain. The within-day CMC originally proposed by Kadaba et al. [7], was firstly reinterpreted in terms of "excluded factors". Then, the new formulation was set to assess the inter-protocol similarity, removing the between-gait-cycle variability. An example showing the effectiveness of the new formulation is presented regarding the pelvis-trunk and ankle kinematics. PMID- 20303273 TI - The association between personality, pain threshold and a single nucleotide polymorphism (rs3813034) in the 3'-untranslated region of the serotonin transporter gene (SLC6A4). AB - In 181 healthy Japanese volunteers we examined the relationship between personality, sensitivity to pain and a single nucleotide polymorphism (rs3813034) in the 3' untranslated region (3' UTR) of the serotonin transporter (5-HTT) gene (SLC6A4). Pain sensitivity was assessed by using cold and pressure thresholds. Personality was assessed by the Temperament and Character Inventory (TCI). Males without the T allele (G/G) showed a significantly higher spiritual acceptance (ST3) score than those who had the T allele (T/T and T/G). Females with the T allele (T/T and T/G) showed significantly higher transpersonal identification (ST2) and self-transcendence (ST) scores than those without the T allele (G/G). As for pain sensitivity and its relationship with TCI, we found a low negative correlation between cold water stimulation, disorderliness (NS4) and novelty seeking (NS) in males, whereas in females we found a low positive correlation between cold water stimulation, self-acceptance (SD4) and pure-hearted principles (C5), as well as pressure stimulation and SD4. It is possible that the 5-HTT 3' UTR gene polymorphism affects the character dimensions of Cloniger's theory, and that there might be a low correlation between pain and a part of the personality. PMID- 20303271 TI - Acidic calcium stores open for business: expanding the potential for intracellular Ca2+ signaling. AB - Changes in cytosolic calcium concentration are crucial for a variety of cellular processes in all cells. It has long been appreciated that calcium is stored and released from intracellular calcium stores such as the endoplasmic reticulum. However, emerging evidence indicates that calcium is also dynamically regulated by a seemingly disparate collection of acidic organelles. In this paper, we review the defining features of these 'acidic calcium stores' and highlight recent progress in understanding the mechanisms of uptake and release of calcium from these stores. We also examine the nature of calcium buffering within the stores, and summarize the physiological and pathophysiological significance of these ubiquitous organelles in calcium signaling. PMID- 20303274 TI - Outcomes of gamma knife treatment for solid intracranial hemangioblastomas. AB - The aim of this study was to examine the results of gamma knife radiosurgery for 13 patients with residual/recurrent or newly diagnosed solid hemangioblastomas. The 13 patients had 34 solid hemangioblastomas, and all patients underwent gamma knife radiosurgery. Seven patients had von Hippel-Lindau disease and six had sporadic disease. When individual lesions were considered, the overall mean dose at the tumor periphery was 15.8 Gy (range: 12-25 Gy) and the average maximum tumor dose was 31.6 Gy (range: 24-50 Gy). The mean duration of follow-up with MRI was 50.2 months. At the last follow-up evaluation, growth control was achieved for all tumors (partial remission in three tumors [8.8%] and no change in 31 tumors [91.2%]). No radiation-related complications were encountered. Our findings reinforce the view that gamma knife radiosurgery is effective and safe for the management of solid hemangioblastomas with a diameter less than 3 cm, whether they are sporadic or associated with von Hippel-Lindau disease. The high response rate and lack of any radiation-induced side-effects confirms the suitability of the doses used in the present study. PMID- 20303276 TI - Effect of knee flexion angle on ground reaction forces, knee moments and muscle co-contraction during an impact-like deceleration landing: implications for the non-contact mechanism of ACL injury. AB - Investigating landing kinetics and neuromuscular control strategies during rapid deceleration movements is a prerequisite to understanding the non-contact mechanism of ACL injury. The purpose of this study was to quantify the effect of knee flexion angle on ground reaction forces, net knee joint moments, muscle co contraction and lower extremity muscles during an impact-like, deceleration task. Ground reaction forces and knee joint moments were determined from video and force plate records of 10 healthy male subjects performing rapid deceleration single leg landings from a 10.5 cm height with different degrees of knee flexion at landing. Muscle co-contraction was based on muscle moments calculated from an EMG-to-moment processing model. Ground reaction forces and co-contraction indices decreased while knee extensor moments increased significantly with increased degrees of knee flexion at landing (all p<0.005). Higher ground reaction forces when landing in an extended knee position suggests they are a contributing factor in non-contact ACL injuries. Increased knee extensor moments and less co contraction with flexed knee landings suggest that quadriceps overload may not be the primary cause of non-contact ACL injuries. The results bring into question the counterbalancing role of the hamstrings during dynamic movements. The soleus may be a valuable synergist stabilizing the tibia against anterior translation at landing. Movement strategies that lessen the propagation of reaction forces up the kinetic chain may help prevent non-contact ACL injuries. The relative interaction of all involved thigh and lower leg muscles, not just the quadriceps and hamstrings should be considered when interpreting non-contact ACL injury mechanisms. PMID- 20303275 TI - Quadriceps strength is not related to gait impact loading in knee osteoarthritis. AB - Joint loading has been implicated in the pathogenesis of knee osteoarthritis (OA). While compartment-specific measures such as the knee adduction moment have received much attention in the literature, less is known about other measures of dynamic loading in this patient population. This cross-sectional study assessed strength and walking patterns of 204 individuals with radiographically confirmed medial tibiofemoral OA and varus malalignment. Pearson product moment correlations and regression analyses were used to determine the bivariate and multivariate relationships amongst measures of impact loading (rate of loading and heelstrike transient occurrence) with demographic, clinical (in particular, radiographic disease severity, lower limb alignment, and self-reported pain and function), and biomechanical variables (maximum voluntary isometric quadriceps strength and gait kinematics). While maximum voluntary isometric quadriceps strength was significantly correlated with rate of loading (r>0.27) when walking at a freely chosen speed, multiple regression analyses indicated that rate of loading was primarily dictated by walking speed (p<0.001), and the effect of quadriceps strength was insignificant when accounting for all other included variables. Individuals who exhibited a heelstrike transient in their vertical ground reaction force profile were significantly more varus malaligned and were more likely to demonstrate severe radiographic degeneration than those who did not exhibit heelstrike transients. These results demonstrate higher impact loading during walking in those with knee OA with faster self-selected walking speeds, though the relationship with quadriceps strength is less clear. Importantly a potential association between disease characteristics, such as malalignment and disease severity, and higher impact loading was also observed. PMID- 20303277 TI - Discovery of inhibitors of brassinin oxidase based on the scaffolds of the phytoalexins brassilexin and wasalexin. AB - Inhibitors of brassinin oxidase (BOLm), a unique phytoalexin detoxifying enzyme produced by the plant pathogenic fungus Leptosphaeria maculans (asexual stage Phoma lingam), were designed based on scaffolds of the phytoalexins brassilexin and wasalexin. Evaluation of these compounds using purified BOLm established that the inhibitory effect of brassilexin and derivatives decreased as follows: 6 chlorobrassilexin approximately 6-bromobrassilexin>5-bromobrassilexin approximately 5-chlorobrassilexin approximately 6-fluorobrassilexin>8 methylbrassilexin>brassilexin approximately 5-fluorobrassilexin. 6 Chlorobrassilexin was determined to be the best competitive inhibitor of BOLm discovered to date, with a K(i)=31microM. Importantly, brassilexin and derivatives did not appear to induce BOLm in fungal cultures. Overall, these results suggest that the brassilexin scaffold is a good lead for further development of paldoxins against L. maculans, as it inhibits competitively BOLm without apparent induction. PMID- 20303278 TI - Synthesis and anticancer activity evaluation of 2(4-alkoxyphenyl)cyclopropyl hydrazides and triazolo phthalazines. AB - A series of new 2(4-alkoxyphenyl)cyclopropyl hydrazide- and triazolo-derivatives were synthesized starting from 4-hydroxycinnamic acid (1) in a clean, mild, efficient and straightforward synthetic protocol. These compounds consisting of different alkoxy substitution, phenylcyclopropyl backbone and different heterocyclic groups were evaluated for in vitro anticancer activity against 4 cell lines displaying certain levels of resistance to pro-apoptotic stimuli and 2 cell lines sensitive to pro-apoptotic compounds. Compounds 7f and 8e were most active and displaying moderate in vitro cytostatic effect through different mechanisms. Significantly, chemically modified derivatives could be obtained in order to develop novel types of compounds aiming to combat apoptosis-resistant cancers, for example, those cancers associated with dismal prognoses. PMID- 20303279 TI - Cranial trauma in ancient Greece: from Homer to classical authors. AB - This article presents literary evidence on traumatic cranio-cerebral injuries in ancient Greece from about 900 B.C. to 100 B.C. The main sources of information are epic and classic Greek texts of that period. Homer provides the first literary source of head trauma, which he portrayed in his epic poems The Iliad and The Odyssey. He describes 41 injuries of the head, face and cervical spine, of which all but two were fatal. Subsequently, other classical authors like Plato, Plutarch and others illustrate cases of cranial trauma that occurred mainly in the battlefields, during athletic games or in unusual accidents. They describe some interesting cases of head trauma in prominent men, such as the poet Aeschylos, the kings Pyrrhos and Kyros and Alexander the Great. Most of these descriptions show that the ancient Greeks possessed very good knowledge of the anatomy of the head and neck region and also of the pathophysiological consequences of trauma in the region. PMID- 20303280 TI - Traumatic arteriovenous fistula of the upper lip: a case report. AB - Traumatic arteriovenous fistula (AVF) is often challenging to diagnose and manage. Those involving the external carotid artery or its branches occur relatively rarely. We present a case of a vascular mass of the upper lip at the right side with a previous history of blunt trauma. AVF of the upper lip can be successfully managed with the preservation of lip function and the cosmetic appearance through surgical excision without embolisation if there is good local access to the lesion. PMID- 20303281 TI - Internal carotid dissection after Le Fort III distraction in Apert syndrome: a case report. AB - A 10-year-old girl with Apert syndrome underwent a Le Fort III osteotomy with the positioning of internal and external distraction devices. The operation was straightforward with no intraoperative complications. Very soon after completion of surgery an anisocoria (unilateral dilation of a pupil) was noticed. This was followed by intracranial oedema which was fatal. The aetiology was dissection of the right internal carotid artery is reported. The complications of Le Fort osteotomies are discussed regarding patients with complex syndromal craniosynostosis and midface hypoplasia, such as Apert syndrome. PMID- 20303282 TI - Virtual dental surgery as a new educational tool in dental school. AB - PURPOSE: The virtual environment of the Voxel-Man simulator that was originally designed for virtual surgical procedures of the middle ear has been adapted to intraoral procedures. To assess application of the simulator to dentistry, virtual apicectomies were chosen as the pilot-test model. METHODS: A group of 53 dental students provided their impressions after virtual simulation of apicectomies in the Voxel-Man simulator. RESULTS: Fifty-one of the 53 students recommended the virtual simulation as an additional modality in dental education. The students indicated that the force feedback (e.g. simulation of haptic pressure), spatial 3D perception, and image resolution of the simulator were sufficient for virtual training of dental surgical procedures. CONCLUSION: The feedback from dental students involved in this pilot-test has encouraged our interdisciplinary group to continue further development of the simulator with the goal of creating new training strategies in dental and medical education. PMID- 20303283 TI - A classification and construction of congenital lateral facial clefts. AB - BACKGROUND: The repair of the lateral or transverse facial cleft is a surgical challenge on the account of the abnormal positioning and appearance of the cleft. MATERIALS AND METHODS: Over a twenty-seven year period, 22 lateral facial cleft cases were evaluated at a cleft lip (CL) and palate clinic and seven children underwent reconstruction of the lateral CL. RESULTS: Twenty-two of 3187 (0.69%) cases presented with a lateral CL. Five of these 22 cases (23%) had a bilateral, eight (36%) had a right-sided and nine (41%) had a left-sided cleft. The evaluation of these cases resulted in a new classification (namely an extension of the Tessier 7 cleft) classification for the cutaneous and muscle involvement: a superior (T7.1), middle (T7.2), inferior (T7.3) and agenetic (T7.4) lateral CL. The altered surgical construction: an internal mucosal straight-line closure, a curved cutaneous-mucosal red-lip/vermilion-lined flap for the lip commissure, muscle reconstruction at the modiolus and a positional cutaneous z-plasty for the rare lateral cutaneous cleft. CONCLUSION: The paper introduced a new classification for the lateral CL, as well as an altered surgical reconstructive technique for the most natural functioning of the lateral part of the face. PMID- 20303284 TI - Association of proinflammatory cytokines with end stage renal disease. AB - CONTEXT: Cytokines play an important role in the pathogenesis of kidney disease and its progression to ESRD. Macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine that is released by macrophages and lymphocytes and interferon-gamma (IFN-gamma) plays an important pathogenetic role in several inflammatory diseases. OBJECTIVES: We have explored the role of MIF -173 G/C, INF gamma +874 A/T and INF-gamma CA repeat microsatellite gene polymorphisms as a susceptibility for ESRD. PARTICIPANTS AND METHODS: We genotyped MIF and IFN-gamma gene polymorphisms in 258 patients with ESRD and 569 healthy controls free of any renal disease using PCR-RFLP, gene sequencing and gene scanning methods. RESULTS: The frequency of high producer MIF -173 CC genotype was higher (10.1%) in ESRD than in controls (1.2%) (p=0.0001, OR=8.9; 95%CI=3.8-21.0). It was observed that there was significant differences in the genotype frequencies of the IFN-gamma +874 A/T at genotypic as well as at allelic level (p=0.0023 and p=0.001) among patients and controls. A significant difference was found in the frequency distribution between the two groups at IFN-gamma CA microsatellite polymorphism (p=0.0001) (CA(17))/(CA(17)). Combined analysis revealed a higher risk ( approximately 9-fold) in ESRD patients with high MIF -173 G/C and high INF-gamma +874 A/T protein producing phenotypes. CONCLUSIONS: These results highlight the role of MIF and IFN-gamma in ESRD disease. PMID- 20303286 TI - Automatic detection of surface EMG activation timing using a wavelet transform based method. AB - The problem of the identification of the muscle contraction timing by using surface electromyographic signal is addressed. The timing detection of the muscular activation in dynamic conditions has a real clinical diagnostic impact. Widely used single threshold methods still rely on the experience of the operator in manually setting that threshold. A new approach to detect the muscular activation intervals, that is based on discontinuities detection in the wavelet domain, is proposed. Accuracy and precision of the algorithm were assessed by using a set of simulated signals obtaining values lower than 11.0 and 8.7 ms for biases and standard deviations of the estimation, respectively. Moreover an experimental application of the algorithm was carried out recruiting a population of 10 able-bodied subjects and processing the myoelectric signals recorded from the lower limb during an isokinetic exercise. The algorithm was able to reveal correctly the timing of muscular activation with performance comparable to the state-of-the-art methods. The detection algorithm is automatic and user independent, it manages the detection of both onset and offset activation, it can be fruitfully applied even in presence of noise and, therefore, it can be used also by unskilled operators. PMID- 20303285 TI - Structural characterization of intact proteins is enhanced by prevalent fragmentation pathways rarely observed for peptides. AB - While collisionally activated dissociation (CAD) pathways for peptides are well characterized, those of intact proteins are not. We systematically assigned CAD product ions of ubiquitin, myoglobin, and bovine serum albumin generated using high-yield, in-source fragmentation. Assignment of >98% of hundreds of product ions implies that the fragmentation pathways described are representative of the major pathways. Protein dissociation mechanisms were found to be modulated by both source declustering potential and precursor ion charge state. Like peptides, higher charge states of proteins fragmented at lower energies next to Pro, via mobile protons, while lower charge states fragmented at higher energies after Asp and Glu, via localized protons. Unlike peptides, however, predominant fragmentation channels of proteins occurred at intermediate charge states via non canonical mechanisms and produced extensive internal fragmentation. The non canonical mechanisms include prominent cleavages C-terminal to Pro and Asn, and N terminal to Ile, Leu, and Ser; these cleavages, along with internal fragments, led to a 45% increase in sequence coverage, improving the specificity of top-down protein identification. Three applications take advantage of the different mechanisms of protein fragmentation. First, modulation of declustering potential selectively fragments different charge states, allowing the source region to be used as the first stage of a low-resolution tandem mass spectrometer, facilitating pseudo-MS(3) of product ions with known parent charge states. Second, development and integration of automated modulation of ion funnel declustering potential allows users access to a particular fragmentation mechanism, yielding facile cleavage on a liquid chromatography timescale. Third, augmentation of a top-down search engine improved protein characterization. PMID- 20303287 TI - Single-row versus double-row arthroscopic rotator cuff repair in small- to medium sized tears. AB - HYPOTHESIS: Double-row rotator cuff repair leads to superior cuff integrity and clinical results compared with single-row repair. MATERIALS AND METHODS: The study enrolled 68 patients with a full-thickness rotator cuff tear who were divided into 2 groups of 34 patients according to repair technique. The patients were followed-up for at least 2 years. The results were evaluated by Constant score. DISCUSSION: Despite the biomechanical studies and cadaver studies that proved the superiority of double-row fixation over single-row fixation, our clinical results show no difference in functional outcome between the two methods. It is evident that double-row repair is more technically demanding, expensive, and time-consuming than single-row repair, without providing a significant improvement in clinical results. RESULTS: Comparison between groups did not show significant differences. At the final follow-up, the Constant score was 82.2 in the single-row group and 78.8 in the double-row group. Functional outcome was improved in both groups after surgery, but the difference between the 2 groups was not significant. CONCLUSIONS: At long-term follow-up, arthroscopic rotator cuff repair with the double-row technique showed no significant difference in clinical outcome compared with single-row repair in small to medium tears. PMID- 20303288 TI - Quality of life and functional outcome after a 2-part proximal humeral fracture: a prospective cohort study on 50 patients treated with a locking plate. AB - BACKGROUND: The aim of the study was to report the 2-year outcome after a displaced 2-part fracture of the proximal humerus in elderly patients treated with a locking plate, including an assessment of the health-related quality of life (HRQoL). MATERIAL AND METHODS: We included 50 patients, mean age 75 (range, 55-93) years with 80% women. The fracture inclusion criteria were a displacement of the shaft of >50% of its width and/or >45 degrees of angulation. Follow-up examinations were performed at 4, 12, and 24 months. The main outcome measures were the Constant and DASH scores and HRQoL according to the EQ-5D. RESULTS: Eight patients (16%) were re-operated upon during the study period. At the final follow-up the mean Constant score was 61 and the mean DASH score 32. The EQ-5D (index) score decreased from 0.86 before the fracture to 0.62 at 4 months. At 12 months the EQ-5D (index) score was 0.65 and at 24 months 0.68. The values at all follow-ups were significantly lower than before the fracture (P < .001 in all 3 comparisons). CONCLUSION: Locking plates appear to be a good treatment alternative in elderly patients with a displaced 2-part fracture of the surgical neck of the proximal humerus with an acceptable complication rate and an acceptable functional outcome; however, rigorous attention has to be paid to avoid screw penetration. Despite the overall acceptable functional outcome, the patients reported a substantial negative effect upon their HRQoL. PMID- 20303289 TI - The effect of medical comorbidity on self-reported shoulder-specific health related quality of life in patients with shoulder disease. AB - BACKGROUND: The purpose of this study was to investigate further the effect of medical comorbidity on a patient reported shoulder specific health related quality of life (HRQoL) measure. We investigated which types of comorbidities have a detrimental effect upon shoulder specific HRQoL. We hypothesized that general medical comorbidity would not negatively affect shoulder specific HRQoL questionnaires, but that comorbidities specific to the chest region would, when properly controlling for other patient factors. METHODS: A cohort of 173 consecutive patients who underwent shoulder surgery for osteoarthritis and/or rotator cuff repair was extracted from a clinical outcomes database. Their health related quality of life (HRQoL) was evaluated with the University of Pennsylvania (PENN) shoulder score and the Short Form-36 (SF-36). Nonadjusted and multivariate risk-adjusted models were built to investigate the effect of medial comorbidity on shoulder specific HRQoL and were tested using linear modeling. RESULTS: Nonadjusted models showed patients with more total comorbidities (P=.01) and more chest-related comorbidities (P=.006) had lower PENN scores. But, when risk adjusting for other patient factors, the PENN scores decreased with an increase in the number of chest comorbidities (P=.008), but not the number of total comorbidites (P=.391) or other (nonchest) comorbidities (P=.163). CONCLUSION: Shoulder specific HRQoL measures are joint specific, but they are influenced by disease or conditions that affect the chest region. This may be important in understanding why patients with certain comorbid diseases report worse shoulder pain and function and may respond differently to treatment over time. PMID- 20303290 TI - Posterior sternoclavicular fracture-dislocation: a case report and novel treatment method. PMID- 20303291 TI - Optimization of glenoid fixation in reverse shoulder arthroplasty using 3 dimensional modeling. AB - BACKGROUND: Reverse shoulder fixation complications may be related to how much glenoid bone is removed and how the fixation screws are located in the glenoid. The purpose of this study was to determine how much bone volume and surface area are lost with incremental reaming and to evaluate screw fixation. METHODS: A contemporary reverse shoulder implant was virtually implanted into models of 6 different shoulders following initial and then after additional incremental reaming was performed. Changes in the glenoid bone surface area and volume available for fixation were statistically evaluated using repeated measures ANOVAs. RESULTS: The total bone volume, the amount of reamed glenoid surface area available for an implant baseplate, and the actual amount of the glenoid in contact with a baseplate decreased with increasing amounts of reaming. With 5 mm of reaming, the total volume decreased by 2810 mm(3), the reamed glenoid surface area decreased by 28%, and the amount of the glenoid in contact with the baseplate decreased by 27%. The amount of engagement of anterior and posterior screws was much less than that of the superior and inferior screws. CONCLUSION: Careful reaming of the glenoid surface is critical, because as little as 1 extra millimeter of bone removal decreases the amount of bone available for implant fixation. After reaming there may not be enough bone to accommodate anterior and posterior screws with the design used in this study. PMID- 20303292 TI - Contact between the coracoacromial arch and the rotator cuff tendons in nonpathologic situations: a cadaveric study. AB - HYPOTHESIS: A recent ultrasound study has shown that impingement phenomenon was observed in healthy shoulders. We hypothesized that nonpathologic contact beneath the coracoacromial arch occurs in normal shoulders. MATERIALS AND METHODS: Seven fresh-frozen cadaveric shoulders were studied. Each specimen was attached to a custom-designed shoulder-positioning device. A 22-N force was applied to the humeral head to keep it centered in the glenoid fossa. Contact pressure beneath the coracoacromial arch was measured by a flexible force sensor during flexion, abduction, internal and external rotation, extension, and horizontal abduction motions. Bending deformation of the coracoacromial ligament was measured by a linear variable differential transducer sensor. Data were recorded with the arm from 0 degrees to maximum range of motion with 10 degrees increments. RESULTS: Contact pressure with the coracoacromial ligament and acromion was not zero in the neutral position and increased during particular motions, such as flexion, abduction, horizontal abduction, and extension, whereas it was almost constant during internal and external rotation. Bending deformation of the coracoacromial ligament during flexion, abduction, and horizontal abduction motions was also shown to be greater than that during internal and external rotation. DISCUSSION: It is possible that repetitive contact of the coracoacromial ligament may cause degenerative changes, and a ridge of proliferative acromial spurs may be the result of nonpathologic contact. CONCLUSIONS: Contact phenomenon of the coracoacromial arch was observed during all motions. Nonpathologic contact beneath the coracoacromial arch may be present in normal shoulders. PMID- 20303293 TI - Diabetes mellitus impairs tendon-bone healing after rotator cuff repair. AB - INTRODUCTION: Studies have demonstrated a significant decrease in skeletal mass, bone mineral density, and impaired fracture healing in the diabetic population. However, the effect of sustained hyperglycemia on tendon-to-bone healing is unknown. MATERIALS AND METHODS: Forty-eight male, Lewis rats underwent unilateral detachment of the supraspinatus tendon followed by immediate anatomic repair with transosseous fixation. In the experimental group (n = 24), diabetes was induced preoperatively via intraperitoneal injection of streptozotocin (STZ, 65 mg/kg) and confirmed with both pre- and post-STZ injection intraperitoneal glucose tolerance tests (IPGTT). Animals were sacrificed at 1 and 2 weeks postoperatively for biomechanical, histomorphometric, and immunohistochemical analysis. Serum hemoglobin A1c (HbA1c) levels were measured at 2 weeks postoperatively. Statistical comparisons were performed using Student t tests with significance set at P < .05. RESULTS: IPGTT analysis demonstrated a significant impairment of glycemic control in the diabetic compared to control animals (P < .05). Mean HbA1c level at 2 weeks postoperatively was 10.6 +/- 2.7% and 6.0 +/- 1.0% for the diabetic and control groups, respectively (P < .05). Diabetic animals demonstrated significantly less fibrocartilage and organized collagen, and increased AGE deposition at the tendon-bone interface (P < .05). The healing enthesis of diabetic animals demonstrated a significantly reduced ultimate load to-failure (4.79 +/- 1.33 N vs 1.60 +/- 1.67 N and 13.63 +/- 2.33 N vs 6.0 +/- 3.24 N for control versus diabetic animals at 1 and 2 weeks, respectively) and stiffness compared to control animals (P < .05). DISCUSSION: Sustained hyperglycemia impairs tendon-bone healing after rotator cuff repair in this rodent model. These findings have significant clinical implications for the expected outcomes of soft tissue repair or reconstructive procedures in diabetic patients with poor glycemic control. PMID- 20303294 TI - Acromion osteolysis and fracture after hook plate fixation for acromioclavicular joint dislocation: a case report. PMID- 20303295 TI - Astrocyte-restricted ablation of interleukin-17-induced Act1-mediated signaling ameliorates autoimmune encephalomyelitis. AB - Interleukin-17 (IL-17) secreted by T helper 17 (Th17) cells is essential in the development of experimental autoimmune encephalomyelitis (EAE). However, it remains unclear how IL-17-mediated signaling in different cellular compartments participates in the central nervous system (CNS) inflammatory process. We examined CNS inflammation in mice with specific deletion of Act1, a critical component required for IL-17 signaling, in endothelial cells, macrophages and microglia, and neuroectoderm (neurons, astrocytes, and oligodendrocytes). In Act1 deficient mice, Th17 cells showed normal infiltration into the CNS but failed to recruit lymphocytes, neutrophils, and macrophages. Act1 deficiency in endothelial cells or in macrophages and microglia did not substantially impact the development of EAE. However, targeted Act1 deficiency in neuroectoderm-derived CNS-resident cells resulted in markedly reduced severity in EAE. Specifically, Act1-deficient astrocytes showed impaired IL-17-mediated inflammatory gene induction. Thus, astroctyes are critical in IL-17-Act1-mediated leukocyte recruitment during autoimmune-induced inflammation of the CNS. PMID- 20303297 TI - Fate mapping reveals separate origins of T cells and myeloid lineages in the thymus. AB - The cellular differentiation pathway originating from the bone marrow leading to early T lymphocytes remains poorly understood. The view that T cells branch off from a lymphoid-restricted pathway has recently been challenged by a model proposing a common progenitor for T cell and myeloid lineages. We generated interleukin-7 receptor alpha (Il7r) Cre recombinase knockin mice and traced lymphocyte development by visualizing the history of Il7r expression. Il7r fate mapping labeled all T cells but few myeloid cells. More than 85% of T cell progenitors were Il7r reporter(+) and, hence, had arisen from an Il7r-expressing pathway. In contrast, the overwhelming majority of myeloid cells in the thymus were derived from Il7r reporter(-) cells. Thus, lymphoid-restricted progenitors are the major route to T cells, and distinct origins of lymphoid and myeloid lineages represent a fundamental hallmark of hematopoiesis. PMID- 20303296 TI - The NLRP3 inflammasome protects against loss of epithelial integrity and mortality during experimental colitis. AB - Decreased expression of the Nlrp3 protein is associated with susceptibility to Crohn's disease. However, the role of Nlrp3 in colitis has not been characterized. Nlrp3 interacts with the adaptor protein ASC to activate caspase-1 in inflammasomes, which are protein complexes responsible for the maturation and secretion of interleukin-1beta (IL-1beta) and IL-18. Here, we showed that mice deficient for Nlrp3 or ASC and caspase-1 were highly susceptible to dextran sodium sulfate (DSS)-induced colitis. Defective inflammasome activation led to loss of epithelial integrity, resulting in systemic dispersion of commensal bacteria, massive leukocyte infiltration, and increased chemokine production in the colon. This process was a consequence of a decrease in IL-18 in mice lacking components of the Nlrp3 inflammasome, resulting in higher mortality rates. Thus, the Nlrp3 inflammasome is critically involved in the maintenance of intestinal homeostasis and protection against colitis. PMID- 20303299 TI - Predictive value of group I oral lesions for HIV infection. AB - OBJECTIVES: Attendees presenting for treatment of acute illness at primary health care facilities in South Africa were assessed to determine the prevalence of human immunodeficiency virus (HIV) infection and the predictability of group I oral lesions (GOLs) for HIV infection. METHODS: This was a cross-sectional analytical study. Patients >18 years of age were recruited and underwent an oral examination and a HIV test. RESULTS: A total of 522 attendees were examined and the HIV prevalence was 40%. None of them were taking antiretroviral drugs. GOLs were diagnosed in 53% of HIV patients, with pseudomembranous and erythematous candidiasis being the most common (38% and 24%, respectively). The average odds and likelihood ratios for multiple lesions were high (32 and 30, respectively) and showed a strong correlation between GOLs and a positive HIV status. CONCLUSION: The prevalence of HIV (40%) and GOLs (53%) was high. GOLs were useful markers of HIV infection, with multiple lesions being highly predictive of HIV infection. PMID- 20303298 TI - Interferon-gamma regulates intestinal epithelial homeostasis through converging beta-catenin signaling pathways. AB - Inflammatory cytokines have been proposed to regulate epithelial homeostasis during intestinal inflammation. We report here that interferon-gamma (IFN-gamma) regulates the crucial homeostatic functions of cell proliferation and apoptosis through serine-threonine protein kinase AKT-beta-catenin and Wingless-Int (Wnt) beta-catenin signaling pathways. Short-term exposure of intestinal epithelial cells to IFN-gamma resulted in activation of beta-catenin through AKT, followed by induction of the secreted Wnt inhibitor Dkk1. Consequently, we observed an increase in Dkk1-mediated apoptosis upon extended IFN-gamma treatment and reduced proliferation through depletion of the Wnt coreceptor LRP6. These effects were enhanced by tumor necrosis factor-alpha (TNF-alpha), suggesting synergism between the two cytokines. Consistent with these results, colitis in vivo was associated with decreased beta-catenin-T cell factor (TCF) signaling, loss of plasma membrane-associated LRP6, and reduced epithelial cell proliferation. Proliferation was partially restored in IFN-gamma-deficient mice. Thus, we propose that IFN-gamma regulates intestinal epithelial homeostasis by sequential regulation of converging beta-catenin signaling pathways. PMID- 20303300 TI - Tumor-infiltrating lymphocytes, particularly the balance between CD8(+) T cells and CCR4(+) regulatory T cells, affect the survival of patients with oral squamous cell carcinoma. AB - OBJECTIVE: The objective of this study was to clarify the prognostic significance of tumor-infiltrating lymphocytes (TILs) in oral squamous cell carcinoma (OSCC); the present study analyzed various TIL-related parameters. STUDY DESIGN: Immunohistochemistry was performed in 87 patients with OSCC for the following TIL related parameters: nest-CD8(+) T cells, stromal CD8(+) T cells, CD4(+) T cells, total regulatory T cells (Tregs), CCR4(+) Tregs, ratio of nest CD8(+) T cells/CCR4(+) Tregs, and ratio of stromal CD8(+) T cells/CCR4(+) Tregs. RESULTS: In univariate analyses, the following parameters were associated with decreased survival: few nest- and stromal CD8(+) T cells and more stromal CCR4(+) Tregs, but not total Tregs. Low ratios of nest and stromal CD8(+) T cell/CCR4(+) Treg were associated with worse survival. In multivariate analysis, the stromal CD8(+) T cell/CCR4(+) Treg ratio was an independent prognostic factor. CONCLUSION: Host immune responses in the stroma of OSCC affect the survival of the patients. The in situ balance between effector T cells and regulatory T cells is the most important factor predicting survival. PMID- 20303301 TI - Use of cone-beam computerized tomography for evaluation of bisphosphonate associated osteonecrosis of the jaws. AB - BACKGROUND AND OBJECTIVE: Bisphosphonate-associated osteonecrosis of the jaws (BONJ) is characterized by exposed nonvital maxillary or mandibular bone. Cone beam computerized tomography (CBCT) is an attractive modality for 3-dimensional imaging of the jaws. The purpose of this study was to compare the clinical and radiographic features of a series of 7 subjects with BONJ who were evaluated by both CBCT and digital panoramic radiography. STUDY DESIGN: Seven subjects with BONJ were evaluated by clinical examination, CBCT, and digital panoramic radiography. RESULTS: Radiographic findings included sclerosis, cortical irregularity, lucency, mottling, fragmentation/sequestra formation, sinus communication, and persistent sockets. There was high correlation between the anatomic location of clinical and radiographic findings. In nearly all cases, CBCT demonstrated a greater extent and quality of changes compared with panoramic radiography. CONCLUSIONS: Cone-beam CT is superior to panoramic radiography in its ability to characterize the nature and extent of radiographic changes in BONJ. Use of CBCT should be strongly considered when radiographic evaluations are included in prospective research investigations of BONJ. However, in the majority of cases of BONJ the clinical significance of improved imaging remains unclear, and therefore specific guidelines for routine clinical care cannot be recommended at this time. PMID- 20303303 TI - Emergency patients: who has the ultimate duty to provide care? PMID- 20303302 TI - Effects of mandibular advancement on upper airway dimension and collapsibility in patients with obstructive sleep apnea using dynamic upper airway imaging during sleep. AB - OBJECTIVES: The objective of this study was to evaluate the effects of mandibular advancement on oropharyngeal dimension and collapsibility and reveal the predominate site of change produced by mandibular advancement in patients with obstructive sleep apnea (OSA). STUDY DESIGN: Sixteen adults (13 males and 3 females) with symptomatic mild to severe OSA participated. Custom-made silicone mandibular positioners were used to keep the mandible at 67% of maximum advancement. Changes in the oropharyngeal size and collapsibility with mandibular advancement were evaluated using ultrafast computed tomography taken during wakefulness and midazolam-induced sleep. Cross-sectional areas were assessed using electron beam tomography at 4 levels: high retropalatal (HRP), low retropalatal (LRP), high retroglossal (HRG), and low retroglossal (LRG). RESULTS: During sleep, the minimum cross-sectional areas decreased 36.5%, 67.8%, 75.5%, and 65.8% at each level of HRP, LRP, HRG, and LRG respectively, as compared with those measured during wakefulness. Mandibular advancement during sleep increased 75.7%, 141.3%, 128.1%, and 119.9% at each level. The oropharynx showed 70.3%, 110.4%, 140.3%, and 156.9% increase in the Collapsibility Indices during sleep at each level of HRP, LRP, HRG, and LRG, respectively, compared with wakefulness. However, collapsibility indices decreased 29.1%, 23.2%, 21.4%, and 34.1% at each level with mandibular advancement. CONCLUSION: Mandibular advancement increases oropharyngeal diameter and decreases oropharyngeal collapsibility during midazolam-induced sleep respiration at the retropalatal as well as the retroglossal region in most patients with OSA. PMID- 20303304 TI - G244E in the canine factor IX gene leads to severe haemophilia B in Rhodesian Ridgebacks. AB - Haemophilia B in Rhodesian Ridgebacks is currently the most important canine haemophilia in Germany. The aim of this study was to define the underlying genetic defect. Genetic studies were performed including six phenotypically affected male dogs (factor IX activity: approximately 1%), four suspected carriers (factor IX activity 48-69%, one confirmed by affected offspring), and 12 healthy dogs. Comparison of the entire coding region of the canine factor IX DNA sequences and exon-intron junctions from affected dogs with the wild type canine factor IX DNA revealed a G-A missense mutation in exon 7. This mutation results in a glycine (GGA) to glutamic acid (GAA) exchange in the catalytic domain of the haemophilic factor IX. All affected dogs were hemizygous for the detected mutation and carriers were heterozygous, whereas none of the Rhodesian Ridgebacks with normal factor IX activity showed the mutation. No further alterations in the sequences between affected dogs and the healthy control group could be observed. None of the Rhodesian Ridgebacks with undefined haemophilia B status (n=30) and no individual of three other dog breeds (Doberman Pinscher: n=20; German Wire haired Pointer: n=20; Labrador: n=25) showed the presence of the mutation. Amino acid sequence alignment and protein structural modelling analysis indicate that the detected mutation causes a relevant functional defect. The results of this study suggest that the detected mutation is responsible for a severe form of haemophilia B in Rhodesian Ridgebacks. PMID- 20303305 TI - Validation of the Warwick-Edinburgh Mental Well-being Scale (WEMWBS) as an overall indicator of population mental health and well-being in the UK veterinary profession. AB - The Warwick-Edinburgh Mental Well-being Scale (WEMWBS) was evaluated as an indicator of mental health and well-being within the veterinary profession in a cross-sectional study among a representative sample of 3200 veterinary surgeons practising in the UK. The WEMWBS mean score for the sample was 48.85 (95% confidence interval 48.43-49.28). The score showed a negative correlation with anxiety and depressive symptoms and a positive correlation with favourable psychosocial working conditions. A 1 unit increase in score was associated with reduced odds of reporting having experienced suicidal thoughts in the previous 12 months, and reduced odds of reporting depressive or anxiety symptoms of clinical significance. The results support the validity of the scale as an overall indicator of population mental health and well-being for this occupational group. PMID- 20303306 TI - Gentle mechanical skin stimulation inhibits the somatocardiac sympathetic C reflex elicited by excitation of unmyelinated C-afferent fibers. AB - The effects of gentle mechanical skin stimulation on reflex discharges in cardiac sympathetic nerve evoked by somatic afferent stimulation were studied in anesthetized rats. Mass discharges were recorded from cardiac sympathetic efferent nerve while somatocardiac sympathetic A- and C-reflexes were elicited by single electrical stimuli to myelinated A- and unmyelinated C-afferent fibers of the tibial nerve. Continuous touch was applied to inner thigh skin with a force of 0.12 N for 10 min periods by a soft elastomer "brush" (1.1cm in diameter with 417 microcones). When touch was applied ipsilateral to the stimulated tibial nerve, the C-reflex was inhibited by up to 40% of its pre-touch amplitude, whereas the A-reflex was unaffected. Inhibition of the C-reflex started during the touch period and lasted for 15 min after cessation of touching. Contralateral touch did not inhibit the C-reflex. The opioid receptor antagonist naloxone attenuated the C-reflex inhibition, but did not abolish it. The C-reflex inhibition was abolished after severing cutaneous nerves innervating inner thigh. We recorded unitary afferent activity from thigh branches of the saphenous nerve and found fibers excited by touch were low-threshold mechanoreceptive Abeta, Adelta and C fibers that have rapidly or slowly adapting properties. In all units tested, average discharge rates during touch period were less than 4 Hz. The results suggest that touch-induced excitation of low threshold cutaneous mechanoreceptive fibers inhibits nociceptive transmission conveyed by C-primary afferents, via the release of both opioid and non-opioid inhibitory mediators. PMID- 20303307 TI - Enhanced sensitivity current density imaging. AB - One of the major weaknesses of current density imaging (CDI) is its poor sensitivity and therefore a need for the use of high voltage in CDI. In this work, a new CDI technique with enhanced sensitivity (ES-CDI) is presented. The ES CDI sequence overcomes the sensitivity problem in samples with a long T(2) relaxation time that allows the use of a long current encoding period. As successful CDI detection is conditioned by a sufficiently large product of current and its application time a longer current encoding period enables the use of lower current and also lower voltage therefore significantly reducing any sample damage. In addition, the ES-CDI sequence also uses fast image signal acquisition and so enables heavy signal averaging and with it associated additional CDI sensitivity increase within the experiment time of the conventional CDI experiment. The feasibility of the ES-CDI sequence was tested on a model sample filled with physiological solution. Voltage of just 1 V and current application time of 800 ms were sufficient to detect current density of 20A/m(2) with a detection limit of 0.7A/m(2). PMID- 20303310 TI - [Use of the pedicled superficial temporoparietal fascial flap for reconstructing soft tissue defects of oral cavity]. AB - INTRODUCTION: The temporoparietal fascial flap is rarely described for the treatment of oral cavity loss of substances. In our experience, it is can a good alternative for the reconstruction of the lateral part of the oral cavity. The aim of this study is to describe the anatomical basis of this technique and to report our recent experience of this flap in this indication. MATERIAL AND PATIENTS: Three fresh cadavers have been dissected in order to determine the maximal length of the flap and the best technique to pass the flap in the oral cavity. Two patients have been operated after surgical resection of an oral epidermoid carcinoma. In one case, the flap has been used to cover a loss of substance of the retromolar and internal cheek areas and in the second case to cover a lateral floor of the mouth loss of substance. RESULTS: The anatomical study showed that the feasibility of the flap was good, the surface of the flap was 12 x 12 centimetres, and the temporal ramus of the facial nerve was easy to preserve if the dissection was prudent in the anterior part of the flap. The clinical results were good, no necrosis of the flap and no facial paralysis were observed. DISCUSSION: In our opinion, this flap can be proposed to cover the lateral loss of substance of the oral cavity. The main advantages of this flap are the absence of visible scar of the donor site, this is a regional flap possible to harvest in the same surgical field, it is independent from the movements of the head and it can be a sensitive flap when the auriculo-temporalis nerve is harvested. PMID- 20303309 TI - (99m)Tc-DTPA diuretic renal scintigraphy in cats with nephroureterolithiasis. AB - The purpose of this study was to evaluate results of diuretic renal scintigraphy in 32 feline kidneys with nephroureterolithiasis and variable degrees of renal pelvis/ureteral dilation. Six kidneys showed a non-obstructive scintigraphic pattern, with a downward slope of time-activity curves (TAC) and a median excretion half-time of radiopharmaceutical (T((1/2))) of 6.09 (5.08-8.43) min. Eight kidneys showed an obstructive pattern, with a continuous rise of TAC and median T((1/2)) of -7.91 (-43.13-0.00) min. In one kidney with presumptive partial obstruction scintigraphic results were equivocal. Seventeen kidneys, most of which had an individual kidney glomerular filtration rate below 0.5ml/min/kg, had non-diagnostic studies. Diuretic renal scintigraphy may be a useful adjunct modality in the diagnosis of ureteral obstruction in some cats if renal function is maintained. However, the large number of non-diagnostic studies in animals with decreased renal function represents a clear limitation of the technique. PMID- 20303311 TI - [Anatomic study and CT angiography with 3D reconstructions of the pulmonary arterial tree]. AB - AIM OF THE STUDY: To prove in vivo and on cadaveric lungs, the constancy of the collateral type of distribution for the right and left pulmonary arteries as described in classical books and modern studies; to estimate the frequency of the main branches observed and define an arterial tree of reference set up with the most common branches for reading the CT pulmonary angiographies. PATIENTS AND METHODS: Sixty three-dimensional reconstructions of pulmonary arterial trees (right: 30; left: 30) using the Volume Rendering Technique (VRT) performed from CT angiographic studies of 30 patients without bronchial, arterial or pulmonary pathology. Dissection of 16 pulmonary arteries from eight fresh cadavers injected with latex. Finally, 76 pulmonary arteries (right: 38; left: 38) were examined. RESULTS: The most common division of the pulmonary artery is a collateral distribution but in seven cases from 38 (18.4%) at right and one case from 38 (2.6%) at left the artery ended in two or three terminal lobar trunks which provided the segmental arteries. The mediastinal artery for the upper right lobe was always found, with a complementary scissural artery in 89.5% of cases; a middle lobar trunk was observed in 22 of the 38 right lungs (57.9%). On the left tree, four different but usually not coexisting mediastinal arteries were identified for the upper lobe, three for the culmen and one for the lingula; six various scissural arteries were noted, three for the culmen and three for the lingula; the segment 6 received one or two segmental arteries, exceptionally three. An arterial tree of reference could be defined for both sides. CONCLUSION: The division in terminal lobar trunks of the pulmonary arteries is a variation demonstrated for the first time. The data obtained from 3D reconstruction imaging in vivo are in conformity with the results of studies performed on injected cadaveric lungs for this point and to define the arterial tree of reference. PMID- 20303308 TI - Gonadal mosaicism of a TAZ (G4.5) mutation in a Japanese family with Barth syndrome and left ventricular noncompaction. AB - TAZ (G4.5) was initially identified as the gene associated with Barth syndrome and left ventricular noncompaction (LVNC). The purpose of this study was to investigate patients with LVNC for disease-causing mutations in TAZ. In 124 Japanese patients, including 50 families, mutation analysis of TAZ was performed using DNA sequencing. A splice donor mutation was identified in two brothers with Barth syndrome and LVNC, and a sister who was asymptomatic. However, the variant was not identified in either parent or the maternal grandparents, all of whom were asymptomatic. Due to the recurrent inheritance of this variant by each of the children we concluded that this was evidence of gonadal mosaicism in the obligate carrier mother, the first reported occurrence of this in Barth syndrome. PMID- 20303312 TI - [Michel Latarjet (1913-1999), surgeon explorer!]. AB - In 1954, Michel Latarjet, anatomist and surgeon of Lyon, developed an original surgical technique to treat the unstable shoulder . This technique since kept his name: "Latarjet". He was a character in 1000 facets: highly skilled anatomist, skillful surgeon, talented sportsman, accomplished musician, big traveler, and many others... An eclectic life, symbol of an abundant XXth century. PMID- 20303313 TI - [Non-vascularized fibular graft as salvage technique for forearm reconstruction]. AB - Authors report a case of a reconstruction of a large bone defect in the forearm with a free fibular graft occurring a good incorporation of the graft. Authors discuss the interest of fibula graft in reconstruction of large bone defect of the forearm. PMID- 20303314 TI - Synthesis of biodiesel from waste cooking oil using sonochemical reactors. AB - Investigation into newer routes of biodiesel synthesis is a key research area especially due to the fluctuations in the conventional fuel prices and the environmental advantages of biodiesel. The present work illustrates the use of sonochemical reactors for the synthesis of biodiesel from waste cooking oil. Transesterification of used frying oil with methanol, in the presence of potassium hydroxide as a catalyst has been investigated using low frequency ultrasonic reactor (20 kHz). Effect of different operating parameters such as alcohol-oil molar ratio, catalyst concentration, temperature, power, pulse and horn position on the extent of conversion of oil have been investigated. The optimum conditions for the transesterification process have been obtained as molar ratio of alcohol to oil as 6:1, catalyst concentration of 1 wt.%, temperature as 45 degrees C and ultrasound power as 200 W with an irradiation time of 40 min. The efficacy of using ultrasound has been compared with the conventional stirring approach based on the use of a six blade turbine with diameter of 1.5 cm operating at 1000 rpm. Also the purification aspects of the final product have been investigated. PMID- 20303315 TI - Finite element model creation and stability considerations of complex biological articulation: The human wrist joint. AB - The finite element method has been used with considerable success to simulate the behaviour of various joints such as the hip, knee and shoulder. It has had less impact on more complicated joints such as the wrist and the ankle. Previously published finite element studies on these multi-bone joints have needed to introduce un-physiological boundary conditions in order to establish numerical convergence of the model simulation. That is necessary since the stabilizing soft tissue mechanism of these joints is usually too elaborate in order to be fully included both anatomically and with regard to material properties. This paper looks at the methodology of creating a finite element model of such a joint focussing on the wrist and the effects additional constraining has on the solution of the model. The study shows that by investigating the effects each of the constraints, a better understanding on the nature of the stabilizing mechanisms of these joints can be achieved. PMID- 20303316 TI - Environmental justice in the therapeutic inner city. AB - Vancouver's Downtown Eastside (DTES) has long been characterized as Canada's skid row within public narratives that raise concerns about communicable diseases, open drug use, survival sex work, and homelessness. This stigmatizing gaze has bolstered a deficit-oriented philosophy that emphasizes measures to mitigate these threats, ostensibly by erasing the moral and environmental depravity from the landscape. However, such measures threaten to further marginalize DTES residents by perpetuating public sentiments of fear and disgust toward the inner city. In this paper, we challenge this orientation by reporting the results of a research process in which DTES residents chronicled their impressions of the neighbourhood. Our findings reveal a paradoxical therapeutic response to environmental injustice in the inner city, one that enables society's most marginalized people to find support, solidarity, and acceptance in their everyday struggles to survive, even thrive, amidst the structural and physical violence of the urban margins. PMID- 20303317 TI - The importance of being parsimonious: reliability of a brief community walkability assessment instrument. AB - This research presents the Leyden Walkability Instrument (LWI), a brief survey checklist designed to measure the perceived walkability of a neighborhood or community where a respondent lives. The reliability of this instrument was tested using the intra-class correlation and found to be moderately substantially reliable (Landis-Koch rating) in every survey item (ranging from .54 to .76 and ranging in observed agreement from 72.8% to 93.9% with an overall instrument score of .71 and an observed agreement of 81.6%). The LWI is discussed in the context of other survey instruments designed to measure perceived walkability and found to be a useful addition because of its brevity and ease of use. PMID- 20303318 TI - Automatic cerebral and cerebellar hemisphere segmentation in 3D MRI: adaptive disconnection algorithm. AB - This paper describes the automatic Adaptive Disconnection method to segment cerebral and cerebellar hemispheres of human brain in three-dimensional magnetic resonance imaging (MRI). Using the partial differential equations based shape bottlenecks algorithm cooperating with an information potential value clustering process, it detects and cuts, first, the compartmental connections between the cerebrum, the cerebellum and the brainstem in the white matter domain, and then, the interhemispheric connections of the extracted cerebrum and cerebellum volumes. As long as the subject orientation in the scanner is given, the variations in subject location and normal brain morphology in different images are accommodated automatically, thus no stereotaxic image registration is required. The modeling of partial volume effect is used to locate cerebrum, cerebellum and brainstem boundaries, and make the interhemispheric connections detectable. The Adaptive Disconnection method was tested with 10 simulated images from the BrainWeb database and 39 clinical images from the LONI Probabilistic Brain Atlas database. It obtained lower error rates than a traditional shape bottlenecks algorithm based segmentation technique (BrainVisa) and linear and nonlinear registration based brain hemisphere segmentation methods. Segmentation accuracies were evaluated against manual segmentations. The Adaptive Disconnection method was also confirmed not to be sensitive to the noise and intensity non-uniformity in the images. We also applied the Adaptive Disconnection method to clinical images of 22 healthy controls and 18 patients with schizophrenia. A preliminary cerebral volumetric asymmetry analysis based on these images demonstrated that the Adaptive Disconnection method is applicable to study abnormal brain asymmetry in schizophrenia. PMID- 20303319 TI - Musculoskeletal MRI segmentation using multi-resolution simplex meshes with medial representations. AB - The automatic segmentation of the musculoskeletal system from medical images is a particularly challenging task, due to its morphological complexity, its large variability in the population and its potentially large deformations. In this paper we propose a novel approach for musculoskeletal segmentation and registration based on simplex meshes. Such discrete models have already proven to be efficient and versatile for medical image segmentation. We extend the current framework by introducing a multi-resolution approach and a reversible medial representation, in order to reduce the complexity of geometric and non penetration constraints computation. Our framework allows both inter and intra patient registration (involving both rigid and elastic matching). We also show that the introduced representations facilitate morphological analysis. As a case study, we demonstrate that muscles, bones, ligaments and cartilages of the hip and the thigh can be registered at an interactive frame rate, in a time-efficient way (<30min), with a satisfactory accuracy ( approximately 1.5mm), and with a minimal amount of manual tasks. PMID- 20303321 TI - Sucrose transporters of higher plants. AB - Recent advances have provided new insights into how sucrose is moved from sites of synthesis to sites of utilisation or storage in sink organs. Sucrose transporters play a central role, as they orchestrate sucrose allocation both intracellularly and at the whole plant level. Sucrose produced in mesophyll cells of leaves may be effluxed into the apoplasm of mesophyll or phloem parenchyma cells by a mechanism that remains elusive, but experimentally consistent with facilitated transport or energy-dependent sucrose/H(+) antiport. From the apoplasm, sucrose/H(+) symporters transport sucrose across the plasma membrane of cells making up the sieve element/companion cell (SE/CC) complex, the long distance conduits of the phloem. Phloem unloading of sucrose in key sinks such as developing seeds involves two sequential transport steps, sucrose efflux followed by sucrose influx. Besides plasma membrane specific sucrose transporters, sucrose transporters on the tonoplast contribute to the capacity for elevated sucrose accumulation in storage organs such as sugar beet roots or sugarcane culms. Except for several sucrose facilitators from seed coats of some leguminous plants all sucrose transporters cloned to date, including recently identified vacuolar sucrose transporters, have been characterised as sucrose/H(+) symporters. Transporters functioning to efflux sucrose into source or sink apoplasms as well as those supporting sucrose/H(+) antiport on tonoplasts, remain to be identified. Sucrose transporter expression and activity is tightly regulated at the transcriptional, post-transcriptional as well as post-translational levels. Light quality and phytohormones play essential regulatory roles and the sucrose molecule itself functions as a signal. PMID- 20303320 TI - Privileged scaffolds for library design and drug discovery. AB - This review explores the concept of using privileged scaffolds to identify biologically active compounds through building chemical libraries. We hope to accomplish three main objectives: to provide one of the most comprehensive listings of privileged scaffolds; to reveal through four selected examples the present state of the art in privileged scaffold library synthesis (in hopes of inspiring new and even more creative approaches); and also to offer some thoughts on how new privileged scaffolds might be identified and exploited. PMID- 20303322 TI - A fully resolved phylogeny of the social amoebas (Dictyostelia) based on combined SSU and ITS rDNA sequences. AB - The dictyostelids possess a complex life cycle including aggregative and multicellular stages. They also include one of the most widely studied protistan model organisms, Dictyostelium discoideum. The current molecular phylogeny of dictyostelids is based largely on SSU (18S) rDNA sequences and shows a deep taxon consisting of four major groups, none of which correspond to the three traditional morphologically-defined genera. However, due to the generally slowly evolving nature of SSU rDNA, these data fail to resolve the majority of branches within the four groups. Given the highly morphologically mixed nature of the dictyostelid groups, it is important to resolve relationships within them. We have determined sequences for the internal transcribed spacers (ITS) of rDNA for nearly all species in the original dictyostelid global phylogeny. Phylogenetic analyses of these data, in combination with the previously determined SSU rDNA sequences, confidently resolve nearly all branches in the tree. This now fully resolved phylogeny confirms the utility of ITS for dictyostelid systematics and lays the ground work for further evolutionary study of the group. PMID- 20303323 TI - Prospective investigation of serum anti-Mullerian hormone concentration in ovulatory intrauterine insemination patients: a preliminary study. AB - This preliminary prospective study investigated serum anti-Mullerian hormone (AMH) through correlations to other basal parameters (123 patients) and according to ovarian response to 75 IU recombinant follicle-stimulating hormone (rFSH)/day (62 patients) in ovulatory patients' first rFSH treatment cycle before intrauterine insemination. Mean age of the patients was 33 years. Serum AMH significantly correlated to age (r=-0.38), antral follicle count (AFC) (r=0.68), ovarian volume (r=0.40), FSH (r=-0.31), (P<0.001) and cycle length (r=0.26, P=0.004). Serum AMH median (interquartile range; IQR) was 8.5 pmol/l (1.9-15.1) in hyporesponders (one mature follicle) versus 10.7 (7.3-17.3) in normal responders (2-3 follicles, with a maximum of two follicles 18 mm and no need for dose reduction) and 13.4 (4.4-24.2) in hyperresponders (>2-3 mature follicles or dose reduction). There was a significant trend over response groups for body weight (P=0.005), body mass index (P=0.035), AFC (P=0.031) and FSH (P=0.001). Serum AMH median (IQR) was 10.6 pmol/l (6.9-18.2) in the 23 patients who achieved an ongoing pregnancy versus 10.5 (5.9-17.2) in the 100 non-pregnant women. Serum AMH may not be the best marker of the ovarian response in these patients. PMID- 20303324 TI - Analysis of factors associated with durable remission of diabetes after Roux-en-Y gastric bypass. AB - BACKGROUND: Data on the durability of remission of type 2 diabetes mellitus (T2DM) after gastric bypass are limited. Our purpose was to identify the rate of long-term remission of T2DM and the factors associated with durable remission. METHODS: A total of 177 patients with T2DM who had undergone Roux-en-Y gastric bypass from 1993 to 2003 had 5-year follow-up data available. T2DM status was determined by interview and evaluation of the diabetic medications. Patients with complete remission or recurrence of T2DM were identified. RESULTS: Follow-up ranged from 5 to 16 years. Of the 177 patients, 157 (89%) had complete remission of T2DM with a decrease in their mean body mass index from baseline (50.2 +/- 8.2 kg/m(2)) to 31.3 +/- 7.2 kg/m(2) postoperatively (mean percentage of excess weight loss 70.0% +/- 18.6%). However, 20 patients (11.3%) did not have T2DM remission despite a mean percentage of excess weight loss of 58.2% +/- 12.3% (P <.0009). Of the 157 patients with initial remission of their T2DM, 68 (43%) subsequently developed T2DM recurrence. Remission of T2DM was durable in 56.9%. Durable (>5-year) resolution of T2DM was greatest in the patients who originally had either controlled their T2DM with diet (76%) or oral hypoglycemic agents (66%). The rate of T2DM remission was more likely to be durable in men (P = .00381). Weight regain was a statistically significant, but weak predictor, of T2DM recurrence. CONCLUSION: Early remission of T2DM occurred in 89% of patients after Roux-en-Y gastric bypass. T2DM recurred in 43.1%. Durable remission correlated most closely with an early disease stage at gastric bypass. PMID- 20303325 TI - Simplified method for the chemical diagnosis of organic aciduria using GC/MS. AB - GC/MS is widely used for the analysis of urinary organic acids for the chemical diagnosis of organic acidurias such as methylmalonic acidemia, propionic acidemia, isovaleric acidemia, glutaric aciduria type I, and multiple carboxylase deficiency. In this study, a rapid and simple preparation method for this analysis was developed in order to improve the laboratory productivity and the working environment. The solvent extraction and trimethylsilyl derivatization steps of the conventional method were improved by reducing the volume of urine sample and extraction solvent and by applying the flash-heater derivatization, respectively. The new method was successfully applied to the chemical diagnoses of five organic acidurias. PMID- 20303326 TI - Determination of the quaternary ammonium compound trospium in human plasma by LC MS/MS: application to a pharmacokinetic study. AB - A highly sensitive, specific and evaporation free SPE extraction, LC-MS/MS method has been developed for the estimation of trospium in human plasma using trospium d8 as an internal standard (IS). The analyte was separated using isocratic mobile phase on reverse phase column and analyzed by MS/MS in the multiple reaction monitoring mode using the respective [M(+)] cations, m/z 392-164 for trospium and m/z 400-172 for the IS. The total run time was 3.50 min and the elution of trospium and trospium-d8 (IS) occurred at 2.8 min. The developed method was validated in human plasma with a lower limit of quantification of 0.05 ng/mL. A linear response function was established for the range of concentrations 0.05-10 ng/mL (r>0.998) for trospium in human plasma. The intra- and inter-day precision values for trospium met the acceptance as per FDA guidelines. Trospium was stable in the battery of stability studies viz., bench-top, auto-sampler, dry extracts and freeze/thaw cycles. The developed assay method was applied to an oral pharmacokinetic study in humans. PMID- 20303327 TI - Characterization of ecdysteroids in Drosophila melanogaster by enzyme immunoassay and nano-liquid chromatography-tandem mass spectrometry. AB - Ecdysteroids are polyhydroxylated steroids that function as molting hormones in insects. 20-Hydroxyecdysone (a 27C-ecdysteroid) is classically considered as the major steroid hormone of Drosophilamelanogaster, but this insect also contains 28C-ecdysteroids. This arises from both the use of several dietary sterols as precursors for the synthesis of its steroid hormones, and its inability to dealkylate the 28C-phytosterols to produce cholesterol. The nature of Drosophila ecdysteroids has been re-investigated using both high-performance liquid chromatography coupled to enzyme immunoassay and a particularly sensitive nano liquid chromatography-mass spectrometry methodology, while taking advantage of recently available ecdysteroid standards isolated from plants. In vitro incubations of the larval steroidogenic organ, the ring-gland, reveals the synthesis of ecdysone, 20-deoxy-makisterone A and a third less polar compound identified as the 24-epimer of the latter, while wandering larvae contain the three corresponding 20-hydroxylated ecdysteroids. This pattern results from the simultaneous use of higher plant sterols (from maize) and fungal sterols (from yeast). The physiological relevance of all these ecdysteroids, which display different affinities to the ecdysteroid receptors, is still a matter of debate. PMID- 20303328 TI - Are we still publishing our presented abstracts from the British Association of Plastic and Reconstructive Surgery (BAPRAS)? PMID- 20303329 TI - Aesthetic aspects of reconstructive clitoroplasty in females with bladder exstrophy-epispadias complex. AB - BACKGROUND: Genital anomalies in females born with classic bladder exstrophy epispadias complex (EEC) include a bifid clitoris and anterior displacement of vagina. The aesthetic aspects of the genitals acquire greater significance with age and may affect self-esteem. We review our experience with clitoral reconstruction in an EEC population with an emphasis on aesthetic outcomes. METHODS: The study group had 26 female patients; three patients with isolated epispadias and 23 with bladder exstrophy. The patients were separated into four separate groups based on reconstructive technique. Group 1 (n=3) had tubularisation of skin between clitoral bodies for urethral reconstruction; group 2 (n=12) underwent staged exstrophy reconstruction; group 3 (n=8) had initial surgery elsewhere and were referred for secondary reconstructive surgery with clitoroplasty accompanied by puboplasty to reconstruct the fourchette; and group 4 (n=3) had total urogenital sinus mobilisation. The aesthetic outcome was assessed subjectively by the surgeon, parent and age-appropriate patient during follow-up. RESULTS: A total of 33 clitoroplasties were performed. Primary clitoroplasty was performed in 18 patients, while a secondary clitoroplasty was done in 15. The follow-up ranged from 3 months to 31 years. Three patients had partial clitoral atrophy and in one patient the gap between clitoral bodies was widely separated and incapable of being joined. Twenty-three of the26 patients (88%) had a satisfactory or excellent aesthetic outcome following clitoroplasty. CONCLUSIONS: Excellent aesthetic outcomes can be achieved by clitoroplasty in EEC patients by using a variety of surgical techniques. We recommend a 'second look' reassessment near puberty to identify poor cosmesis and offer secondary clitoroplasty to improve aesthetic outcome. PMID- 20303330 TI - Maxillomandibular distraction osteogenesis for Marshall-Smith syndrome. AB - The Marshall-Smith syndrome is a very rare disorder with early overgrowth and was first reported by Marshall et al. in 1971. Patients with the Marshall-Smith syndrome have characteristic facial features and systemic congenital abnormalities. In many cases, patients die early in the postnatal period due to respiratory disorders. We treated a male child with this syndrome with plastic surgery to improve facial features - the first effort of its kind in the world. We report good results from the surgery. The treatment included bilateral mandibular distraction osteogenesis for micrognathia and tracheostomy weaning. Six months later, LeFort III maxillary distraction osteogenesis was performed for maxillary hypoplasia. The clinical course was uneventful after both surgeries. At the time of this report, facial appearance and occlusal conditions have improved markedly, although the tracheal stoma could not be closed. The patient is a long term survivor of this condition. After considering quality-of-life issues for the patient, surgical treatment was offered for facial dysmorphism. This type of effort has not yet been reported in the literature. For patients with the Marshall-Smith syndrome who are expected to survive long, surgical treatment should be strongly considered to improve the quality of life of the affected child. PMID- 20303331 TI - Impact of medical discipline and observer gender on cosmetic outcome evaluation in breast reconstruction using transverse rectus abdominis myocutaneous (TRAM) flap and radiotherapy. AB - BACKGROUND: Despite the complication rate, the majority of studies report a satisfactory cosmetic outcome in patients undergoing transverse rectus abdominis myocutaneous (TRAM) flap breast reconstruction both before and after radiotherapy (RT). The lack of a universal agreement on the use of a validated scale for cosmetic assessment in clinical practise leads to subjective criteria of evaluation and causes a great deal of interobserver variability. This study investigates whether there is any difference in the evaluation of cosmesis according to gender and specialisation of the observer. METHODS: Fifty-two photographs of the patients who had undergone TRAM reconstruction for breast cancer, divided into three groups according to the treatment (TRAM only, TRAM >RT, RT->TRAM), were evaluated by 21 specialists, 10 male and 11 female from radiotherapy, breast surgery and plastic reconstructive surgery. Cosmetic outcome was classified using the four-category Harvard scale: a score of excellent/good was considered acceptable. RESULTS: The overall rate of good/excellent ratings was 66.6%, which was lower than the score reported in the literature. A significantly worse score was registered in the TRAM->RT group compared with the other groups. The probability for male physicians to award a positive judgement is 24% higher than that of female ones. In general, there is a decent agreement among the judgement raters. CONCLUSIONS: No statistically significant difference in cosmetic evaluation was noted overall between male physicians and female ones. However, within each specialisation, the difference between the two genders was great. Breast surgeons gave the worst opinion, and among them female surgeons judged most severely, whereas plastic surgeons gave the best opinion, and among them females provided the highest favourable judgement. PMID- 20303332 TI - Quantified proarrhythmic potential of selected human embryonic stem cell-derived cardiomyocytes. AB - To improve proarrhythmic predictability of preclinical models, we assessed whether human ventricular-like embryonic stem cell-derived cardiomyocytes (hESC CMs) can be selected following a standardized protocol. Also, we quantified their arrhythmogenic response and compared this to a contemporary used rabbit Purkinje fiber (PF) model. Multiple transmembrane action potentials (AP) were recorded from 164 hESC-CM clusters (9 different batches), and 12 isolated PFs from New Zealand White rabbits. AP duration (APD), early afterdepolarizations (EADs), triangulation (T), and short-term variability of repolarization (STV) were determined on application of the I(Kr) blocker E-4031 (0.03/0.1/0.3/1 muM). Isoproterenol (0.1 muM) was used to assess adrenergic response. To validate the phenotype, RNA isolated from atrial- and ventricular-like clusters (n=8) was analyzed using low-density Taqman arrays. Based on initial experiments, slow beating rate (<50 bpm) and long APD (>200 ms) were used to select 31 ventricular like clusters. E-4031 (1 muM) prolonged APD (31/31) and induced EADs only in clusters with APD90>300 ms (11/16). EADs were associated with increased T (1.6+/ 0.2 vs 2.0+/-0.3) and STV (2.7+/-1.5 vs 6.9+/-1.9). Rabbit PF reacted in a similar way with regards to EADs (5/12), increased T (1.3+/-0.1 vs 1.9+/-0.4), and STV (1.2+/-0.9 vs 7.1+/-5.6). According to ROC values, hESC-CMs (STV 0.91) could predict EADs at least equivalent to PF (STV 0.69). Isoproterenol shortened APD and completely suppressed EADs. Gene expression analysis revealed that HCN1/2, KCNA5, and GJA5 were higher in atrial/nodal-like cells, whereas KCNJ2 and SCN1B were higher in ventricular-like cells (P<0.05). Selection of hESC-CM clusters with a ventricular-like phenotype can be standardized. The proarrhythmic results are qualitatively and quantitatively comparable between hESC-CMs and rabbit PF. Our results indicate that additional validation of this new safety pharmacology model is warranted. PMID- 20303333 TI - Conditional deletion of Stat3 promotes neurogenesis and inhibits astrogliogenesis in neural stem cells. AB - Although signal transducer and activator of transcription 3 (Stat3) plays crucial roles in the determination of neural stem cell (NSC) fate, Stat3 has multiple roles in NSC function. Moreover, Stat3 plays important roles in neuronal survival and tumorigenesis. To investigate the overall effects of Stat3 on NSC fate, NSC were isolated from Stat3(flox/flox) mouse embryos (E14-15d), in which both Stat3 alleles are flanked by LoxP sites. Isolated NSC was inoculated with an adenovirus vector expressing Cre recombinase (Ad.nCre) or a control adenovirus vector expressing beta-galactosidase (Ad.nLz). Three days later, quantitative real-time PCR (qPCR) analysis revealed that treatment with Ad.nCre eliminated stat3 mRNA expression in NSC. Promoter assay confirmed that overexpression of nCre inhibited transactivation of acute responsive element (APRE) and blocked Stat3 function in NSC. Moreover, Western blot analysis and immunocytochemical analysis revealed that elimination of Stat3 in NSC promoted neurogenesis and inhibited astrogliogenesis. In addition, we investigated the effects of Stat3 elimination in NSC on the mRNA expression of Notch family members and bHLH factors. Consequently, qPCR analysis showed that elimination of Stat3 in NSC promoted neurogenesis and inhibited astrogliogenesis through down-regulation of notch1, notch2 and hes5, but not hes1 mRNA expression. PMID- 20303334 TI - DNA-PK/Ku complex binds to latency-associated nuclear antigen and negatively regulates Kaposi's sarcoma-associated herpesvirus latent replication. AB - During latent infection, latency-associated nuclear antigen (LANA) of Kaposi's sarcoma-associated herpesvirus (KSHV) plays important roles in episomal persistence and replication. Several host factors are associated with KSHV latent replication. Here, we show that the catalytic subunit of DNA protein kinase (DNA PKcs), Ku70, and Ku86 bind the N-terminal region of LANA. LANA was phosphorylated by DNA-PK and overexpression of Ku70, but not Ku86, impaired transient replication. The efficiency of transient replication was significantly increased in the HCT116 (Ku86 +/-) cell line, compared to the HCT116 (Ku86 +/+) cell line, suggesting that the DNA-PK/Ku complex negatively regulates KSHV latent replication. PMID- 20303335 TI - Biochemical characterization of the binding of cyclic RGDyK to hepatic stellate cells. AB - Activated hepatic stellate cells (HSCs) play a crucial role in the development of liver fibrosis. Noninvasive monitoring of the activation of HSCs has been challenging due to the lack of specific receptors or motifs on the cells. The present study provides the evidence that integrin alpha v beta 3 expressed on HSCs is a biomarker reflecting the activation of HSCs. Solid-phase synthesis of cRGDyK (Arg-Gly-Asp-(D)Tyr-Lys) peptide and FAM-conjugated peptide were employed for binding to integrin alpha v beta 3. The increased expression of integrin alpha v and beta 3 at mRNA and protein levels was detected during HSC activation. The affinity of cRGDyK to integrin alpha v beta 3 was examined by both radioligand binding assay and FAM-conjugated peptide binding measurements. Quantitative RT-PCR and Western blotting showed a less dramatic, but significant increase in alpha v and beta 3 integrin mRNA and protein expression following activation of rat HSCs. Radioiodinated cRGDyK binds to both purified and membrane bound integrin alpha v beta 3 with high affinity in a dissociable manner. FAM conjugated cRGDyK was coupled to activated HSCs in a time- and dose-dependent, receptor-mediated manner. Activated HSCs express sufficient number of integrin alpha v beta 3 receptor. cRGDyK peptide binds to both purified and membrane-bound integrin alpha v beta 3 with high affinity in a reversible fashion. Thus, the cRGDyK peptide represented a new agent potentially useful for the diagnosis of liver fibrosis. PMID- 20303336 TI - The signalling role of action potential depolarization in insulin secretion: metabolism-dependent dissociation between action potential increase and secretion increase by TEA. AB - The K(+) channel blocker, TEA is known to increase action potential amplitude and insulin secretion of mouse beta-cells when added to a nutrient secretagogue. In the presence of a maximally effective sulfonylurea concentration (2.7 microM glipizide) the nutrient secretagogue alpha-ketoisocaproic acid (KIC, 10mM) strongly increased insulin secretion (about elevenfold). Instead of enhancing the effect of KIC, TEA reduced the KIC-induced secretion by more than 50%. Also, the secretion rate produced by 2.7 microM glipizide alone was significantly reduced by TEA. In contrast, TEA enhanced the insulinotropic effect of glipizide when a basal glucose concentration (5mM) was present. In the presence as well as in the absence of glucose glipizide produced a plateau depolarization with superimposed action potentials. Under both conditions, TEA increased the glipizide-induced action potential amplitude and further elevated the cytosolic free calcium concentration ([Ca(2+)](i)) with an oscillatory characteristic. These effects depended on the activity of L-type Ca(2+) channels, even though the effect of TEA differed from that of 1 microM of the Ca(2+) channel opener, Bay K8644, which primarily increased action potential duration. TEA did not negatively affect parameters of beta-cell energy metabolism (NAD(P)H fluorescence and ATP/ADP ratio), rather, it slightly increased NAD(P)H fluorescence. Apparently, TEA inhibits insulin secretion in the absence of glucose in spite of a persistent ability to block K(+) ion conductance. Thus, the signalling role of action potential depolarization in insulin secretion may require reconsideration and ion conductance-independent actions of K(+) channels may be involved in this paradox effect of TEA. PMID- 20303337 TI - Glycine transporter 1 (GlyT1) inhibitors exhibit anticonvulsant properties in the rat maximal electroshock threshold (MEST) test. AB - Glycine can act as either an inhibitory neurotransmitter or as a potentiator of NMDA-dependent excitatory neurotransmission. There is some evidence that glycine can have both pro- and anticonvulsant properties in various rodent models of epilepsy. In the present study we tested several glycine transporter 1 (GlyT1) inhibitors including NFPS, SSR 504734, Lu AA21279, Org 25935, SB-710622, GSK931145, as well as the glycine agonist d-serine, in the maximal electroshock threshold (MEST) test in the rat. In a series of experiments, male Sprague-Dawley rats (n=12/group) were pre-treated with a compound of interest and then received an electric shock delivered via corneal electrodes. A cohort of satellite animals (n=3/group) was also used to measure blood and brain levels of Org 25935. All GlyT1 inhibitors increased seizure thresholds dose-dependently, indicative of anticonvulsant activity. SB-710622 and GSK931145 had lower minimum effective doses (MEDs) in the MEST test than other GlyT1 inhibitors. At estimated t(max), increases in dose administered were paralleled by increases in blood and brain concentrations of Org 25935. Thus, increasing extracellular concentration of glycine via inhibition of its uptake protects from electroshock-induced seizures in the rat. Whether strychnine-sensitive or strychnine-insensitive glycine binding sites are involved in this effect remains to be determined. PMID- 20303338 TI - Effects of quercetin on the sleep-wake cycle in rats: involvement of gamma aminobutyric acid receptor type A in regulation of rapid eye movement sleep. AB - The bioflavonoid quercetin is widely found in plants and exerts a large number of biological activities such as anti-hypertensive and anti-inflammatory properties. However, the effect of quercetin on the sleep-wake cycle has not been investigated. In the present study, we investigated the effect of quercetin on sleep-wake regulation. Intraperitoneal administration of quercetin (200mg/kg) significantly increased non-rapid eye movement (non-REM) sleep during dark period in rats, while it significantly decreased REM sleep. The decrease in REM sleep induced by quercetin was blocked by intracerebroventricular (i.c.v.) injection of bicuculline, a GABA(A) receptor antagonist. In contrast, the increase in non-REM sleep induced by quercetin was not affected by i.c.v. injection of bicuculline. Therefore, the present results suggest that quercetin alters the sleep-wake cycle partly through activation of GABA(A) receptors. PMID- 20303339 TI - Characterizing iron deposition in Parkinson's disease using susceptibility weighted imaging: an in vivo MR study. AB - Brain-iron deposition has been proposed to play an important role in the pathophysiology of Parkinson's disease (PD). The aim of this study was to evaluate the feasibility of characterizing iron deposition in PD using susceptibility-weighted imaging (SWI), and to investigate the correlation of brain-iron accumulation with the clinical status in patients with PD. Forty patients with PD without dementia and 26 age- and sex-matched healthy controls underwent high-resolution susceptibility-weighted magnetic resonance (MR) imaging. The phase shift values of the bilateral red nucleus (RN), substantia nigra (SN), caudate nucleus (CA), globus pallidus (GP), putamen (PU), thalamus (TH) and frontal white matter (FWM) were examined for their relationship with the clinical status. The iron concentrations of the regions involved in PD, such as the SN, increased more significantly, while those in other regions of interest (ROI) did not elevate significantly. No correlation between the increase of the iron concentrations of the SN and duration of PD was observed. PD, however, was closely associated with the Unified Parkinson's Disease Rating Scale motor score (UPDRS-III). No significant differences were found between earlier-onset and later-onset PD patients in terms of the iron concentrations of the SN. Brain-iron concentration can be evaluated by SWI. Also, the brain-iron concentration in the SN correlated with UPDRS motor score, indicating that iron concentration can function as an in vivo biomarker to objectively evaluate the status of PD. PMID- 20303340 TI - Interhemispheric difference in susceptibility to epileptogenesis: evidence from the audiogenic kindling model in Wistar rats. AB - Audiogenic kindling (AK) represents a model of naturally occurring epileptogenesis in which intensification of repeatedly induced audiogenic seizures results from propagation of epileptic activity from the brainstem to forebrain. Previously it has been shown that unilateral cortical spreading depression (SD) is a reliable earliest manifestation of mild AK produced by repetition of minimal audiogenic seizures (running) in Wistar rats. The unilateral triggering SD suggests the existence of asymmetry in the forebrain recruitment during the kindling and the present study examined whether epileptogenesis produced by this mild AK paradigm is a lateralized process. Twenty five running episodes were induced by brief sound stimulation in Wistar rats susceptible to audiogenic seizures. Behavioral and EEG correlates of AK development were assessed. Running behavior elicited by brief sound stimulation had an asymmetrical pattern with profound preference for one direction. Most rats expressing leftward running displayed full kindling development whereas the majority of rats with rightward running were resistant to AK. The EEG marker of AK, a cortical epileptiform discharge, was recorded only in rats with leftward running and the first discharge appeared in the left cortex. Cortical SD was recorded after repeated running seizures in all rats with reproducible audiogenic response irrespective of the running lateralization and propensity to kindling. Until the late kindling stages, SD was triggered unilaterally in the cortex ipsilateral to the running direction. These findings indicate intrinsically determined lateralization of epileptogenic process in the mild AK model and enhanced vulnerability of the left hemisphere to epileptogenesis. PMID- 20303341 TI - Characterizing the persistent CA3 interneuronal spiking activity in elevated extracellular potassium in the young rat hippocampus. AB - Seizures coincide with an increase in extracellular potassium concentrations [K(+)](e) yet little information is available regarding this phenomenon on the firing pattern, frequency and neuronal properties of inhibitory neurons responsible for modulating network excitability. Therefore, we investigated the effects of elevating [K(+)](e) from 2.5 to 12.5mM on CA3 rat hippocampal interneurons in vitro using whole-cell patch-clamp recordings. We found that the majority of interneurons (21/25) in artificial cerebral spinal fluid (aCSF) exhibited spontaneous tonic spiking activity. As the [K(+)](e) increased to 12.5mM, interneurons exhibited a tonic, irregular, burst firing activity, or a combination of these. The input resistance decreased significantly to 59+/-18% at 7.5mM K(+) and did not further change at higher [K(+)](e) while the amount of K(+)-induced depolarization significantly increased from 5 to 12.5mM K(+) perfusion; a depolarization block occurred in 4 of the 12 interneurons at 12.5mM. Also, as [K(+)](e) increased, a transition from lower (1.3+/-0.6Hz) to higher dominant peak frequency (15.0+/-5.0Hz) was observed. We found that non-fast spiking (NFS) interneurons represented the majority of cells recorded and exhibited mostly tonic firing activity in raised K(+). Fast spiking (FS) interneurons predominately had a tonic firing pattern with very few exhibiting bursting activity in elevated K(+). In conclusion, we report that raised [K(+)](e) in amounts observed during seizures increases hippocampal CA3 interneuronal activity and suggests that a loss or impairment of inhibitory function may be present during these events. PMID- 20303344 TI - Diagnostic accuracy of sTREM-1 to identify infection in critically ill patients with systemic inflammatory response syndrome. AB - OBJECTIVES: To assess the accuracy of plasma levels of soluble Triggering Receptor Expressed on Myeloid cells (sTREM)-1 to diagnose infection in critical patients with systemic inflammatory response syndrome (SIRS). DESIGN AND METHODS: We prospectively studied 114 patients with SIRS criteria. The patients' plasma levels of sTREM-1 were measured within 24h of admission to the intensive care unit. The final diagnosis of infection was made independently by two investigators, who were blinded to the levels of sTREM-1. RESULTS: The area under the ROC curve of sTREM-1 for the diagnosis of sepsis was 0.62 (95% confidence interval [95% CI] 0.51-0.72). The diagnostic odds ratio of sTREM-1 after adjusting for the Infection Probability Score and procalcitonin plasma levels was 1.81 (95% CI 0.66-4.98; p=0.2508). CONCLUSIONS: In critical patients admitted with SIRS, sTREM-1 has poor discriminative power to identify patients with infection, and sTREM-1 levels do not add diagnostic information to that provided by other routinely available clinical tests. PMID- 20303343 TI - The relationship between transient zinc ion fluctuations and redox signaling in the pathways of secondary cellular injury: relevance to traumatic brain injury. AB - A major obstacle that hampers the design of drug therapy for traumatic brain injury is the incomplete understanding of the biochemical pathways that lead to secondary cellular injury and contribute to cell death. One such pathway involves reactive species that generate potentially cytotoxic zinc ion fluctuations as a major executor of neuronal, and possibly glial, cell death. Whether zinc ions released during traumatic brain injury are toxic or protective is controversial but can be approached by investigating the exact concentrations of free zinc ions, the thresholds of compromised zinc buffering capacity, and the mechanism of cellular homeostatic control of zinc. Rapidly stretch-injured rat pheochromocytoma (PC12) cells express cellular zinc ion fluctuations that depend on the production of nitric oxide. Chelation of cellular zinc ions after rapid stretch injury, however, increases cellular reactive oxygen species. In a rat model of traumatic brain injury, parasagittal fluid percussion, analysis of the metal load of metallothionein was used as an indicator of changes in cellular zinc ion concentrations. The combined results from the cellular and in vivo investigations caution against interpreting zinc ion fluctuations in the early phase (24h) after injury as a primarily cytotoxic event. PMID- 20303342 TI - MicroRNA dysregulation in psychiatric disease. AB - MicroRNAs (miRNAs) are small regulatory RNAs that individually regulate up to several hundred genes, and collectively may regulate as much as two-thirds of the transcriptome. Recent evidence supports a role for miRNA dysregulation in psychiatric and neurological disorders, including schizophrenia, bipolar disorder, and autism. Small changes in miRNA expression can fine-tune the expression of multiple genes within a biological network, suggesting that miRNA dysregulation may underlie many of the molecular changes observed in psychiatric disease, and that therapeutic regulation of miRNA levels may represent a novel treatment option. PMID- 20303345 TI - Additive and global functions of HoxA cluster genes in mesoderm derivatives. AB - Hox genes encode transcription factors that play a central role in the specification of regional identities along the anterior to posterior body axis. In the developing mouse embryo, Hox genes from all four genomic clusters are involved in range of developmental processes, including the patterning of skeletal structures and the formation of several organs. However, the functional redundancy observed either between paralogous genes, or among neighboring genes from the same cluster, has hampered functional analyses, in particular when synergistic, cluster-specific functions are considered. Here, we report that mutant mice lacking the entire HoxA cluster in mesodermal lineages display the expected spectrum of postnatal respiratory, cardiac and urogenital defects, previously reported for single gene mutations. Likewise, mild phenotypes are observed in both appendicular and axial skeleton. However, a striking effect was uncovered in the hematopoietic system, much stronger than that seen for Hoxa9 inactivation alone, which involves stem cells (HSCs) as well as the erythroid lineage, indicating that several Hoxa genes are necessary for normal hematopoiesis to occur. Finally, the combined deletions of Hoxa and Hoxd genes reveal abnormalities in axial elongation as well as skin morphogenesis that are likely the results of defects in epithelial-mesenchymal interactions. PMID- 20303346 TI - The cyclic pattern of blood alcohol levels during continuous ethanol feeding in rats: the effect of feeding S-adenosylmethionine. AB - S-adenosylmethionine (SAMe), the major methyl donor for DNA and histone methylation was fed with ethanol for 1month in order to modify the effects of ethanol on rat liver. The following parameters were studied to determine the effects of SAMe; liver histology, the blood alcohol cycle (BAL), changes in gene expression mined from microarray analysis, changes in histone methylation, changes in liver SAMe levels and its metabolites and ADH. SAMe changed the type of fatty liver, reduced liver ALT levels and prevented the BAL cycle caused by intragastric ethanol feeding. Microarray analysis showed that SAMe feeding prevented most of the changes in gene expression induced by ethanol feeding, presumably by inducing H3K27me3 and gene silencing. H3K27me3 was significantly increased by SAMe with or without ethanol feeding. It is concluded that SAMe feeding stabilized global gene expression so that the changes in gene expression involved in the blood alcohol cycle were prevented. PMID- 20303347 TI - Acute intrastriatal administration of quinolinic acid provokes hyperphosphorylation of cytoskeletal intermediate filament proteins in astrocytes and neurons of rats. AB - In the present study we investigated the effect of in vivo intrastriatal injection of quinolinic acid (QA) on cytoskeletal proteins in astrocytes and neurons of young rats at early stage (30 min) after infusion. QA (150 nmoles/0.5 microL) significantly increased the in vitro phosphorylation of the low molecular weight neurofilament subunit (NFL) and the glial fibrillary acidic protein (GFAP) of neurons and astrocytes, respectively. This effect was mediated by cAMP dependent protein kinase A (PKA), protein kinase C (PKC) and Ca(2+)/calmodulin dependent protein kinase II (PKCaMII). In contrast, mitogen activated protein kinases were not activated by QA infusion. Furthermore, the specific N-methyl-D aspartate (NMDA) antagonist MK-801 (0.25 mg/kg i.p), the antioxidant L-NAME (60 mg?kg?day), and diphenyldisselenide (PheSe)(2) (0.625 mg?kg?day) injected prior to QA infusion totally prevented QA-induced cytoskeletal hyperphosphorylation. We also observed that QA-induced hyperphosphorylation was targeted at the Ser55 phosphorylating site on NFL head domain, described as a regulatory site for NF assembly in vivo. This effect was fully prevented by MK801, by the PKA inhibitor H89 and by (PheSe)(2), whereas staurosporine (PKC inhibitor) only partially prevented Ser55 phosphorylation. The PKCaMII inhibitor (KN93) and the antioxidant L-NAME failed to prevent the hyperphosphorylation of Ser55 by QA infusion. Therefore, we presume that QA-elicited hyperphosphorylation of the neural cytoskeleton, and specially of NFLSer55, achieved by intrastriatal QA injection could represent an early step in the pathophysiological cascade of deleterious events exerted by QA in rat striatum. Our observations also indicate that NMDA mediated Ca(2+) events and oxidative stress may be related to the altered protein cytoskeleton hyperphosphorylation observed with important implications for brain function. PMID- 20303348 TI - Hyperammonemia induces neuroinflammation that contributes to cognitive impairment in rats with hepatic encephalopathy. AB - BACKGROUND & AIMS: Hyperammonemia and inflammation cooperate to induce neurological alterations in hepatic encephalopathy. Recent studies in animal models suggest that chronic hyperammonemia and neuroinflammation impair learning ability by the same mechanism. Chronic hyperammonemia might induce inflammatory factors in the brain that impair cognitive function. We sought to determine whether hyperammonemia itself induces neuroinflammation, whether ammonia-induced neuroinflammation mediates cognitive impairment, and whether neuroinflammation also occurs in rats with bile duct ligation (BDL rats)-a model of chronic liver injury that results in hyperammonemia and hepatic encephalopathy. METHODS: Chronic moderate hyperammonemia was induced by feeding male Wistar rats an ammonium-containing diet or performing BDL. Rats that received a standard diet or a sham operation were used as controls. Neuroinflammation was assessed by measuring activation of microglia and inflammatory factors. Brain samples were collected from hyperammonemic and BDL rats; microglial activation was determined by immunohistochemistry and quantification of inflammatory markers (ie, inducible nitric oxide synthase, interleukin-1beta, and prostaglandin E2). Learning ability and motor activity were assessed in hyperammonemic and BDL rats given ibuprofen as an anti-inflammatory agent. RESULTS: Chronic moderate hyperammonemia or BDL activated the microglia, especially in cerebellum; increased inducible nitric oxide synthase, interleukin-1beta, and prostaglandin E2 levels; and impaired cognitive and motor function, compared with controls. Ibuprofen reduced microglial activation and restored cognitive and motor functions in the hyperammonemic and BDL rats. CONCLUSIONS: Chronic hyperammonemia is sufficient to induce microglial activation and neuroinflammation; these contribute to the cognitive and motor alterations that occur during hepatic encephalopathy. PMID- 20303349 TI - A novel role for the dioxin receptor in fatty acid metabolism and hepatic steatosis. AB - BACKGROUND & AIMS: The aryl hydrocarbon receptor (AhR) also known as the dioxin receptor or xenobiotic receptor is a member of the basic helix-loop-helix/period AhR nuclear translocator single minded family. The goal of this study was to determine the endobiotic role of AhR in hepatic steatosis. METHODS: Wild-type, constitutively activated AhR transgenic, AhR null and CD36/fatty acid translocase null mice were used to investigate the role of AhR in steatosis and the involvement of CD36 in the steatotic effect of AhR. The promoters of the mouse and human CD36 genes were cloned and their regulation by AhR was analyzed. RESULTS: Activation of AhR induced spontaneous hepatic steatosis characterized by the accumulation of triglycerides. The steatotic effect of AhR likely is owing to the combined up-regulation of CD36 and fatty acid transport proteins, suppression of fatty acid oxidation, inhibition of hepatic export of triglycerides, increase in peripheral fat mobilization, and increased hepatic oxidative stress. Promoter analysis established CD36 as a novel transcriptional target of AhR. Activation of AhR in liver cells induced CD36 gene expression and enhanced fatty acid uptake. The steatotic effect of an AhR agonist was inhibited in CD36-/- mice. CONCLUSIONS: Our study reveals a novel link between AhR-induced steatosis and the expression of CD36. Industrial or military exposures to dioxin and related compounds have been linked to increased prevalence of fatty liver in human beings. Results from this study may help to establish AhR and its target CD36 as novel therapeutic and preventive targets for fatty liver disease. PMID- 20303350 TI - Dasatinib inhibits the development of metastases in a mouse model of pancreatic ductal adenocarcinoma. AB - BACKGROUND & AIMS: Pancreatic ductal adenocarcinoma (PDAC) is a highly invasive and metastatic disease for which conventional treatments are of limited efficacy. A number of agents in development are potential anti-invasive and antimetastatic agents, including the Src kinase inhibitor dasatinib. The aim of this study was to assess the importance of Src in human PDAC and to use a genetically engineered mouse model of PDAC to determine the effects of dasatinib on PDAC progression. METHODS: Src expression and activity was measured by immunohistochemistry in 114 human PDACs. Targeting expression of Trp53(R172H) and Kras(G12D) to the mouse pancreas results in the formation of invasive and metastatic PDAC. These mice were treated with dasatinib, and disease progression monitored. Cell lines were derived from mouse PDACs, and in vitro effects of dasatinib assessed. RESULTS: Src expression and activity were up-regulated in human PDAC and this correlated with reduced survival. Dasatinib inhibited the migration and invasion of PDAC cell lines, although no effects on proliferation were seen at concentrations that inhibited Src kinase activity. In addition, dasatinib significantly inhibited the development of metastases in Pdx1-Cre, Z/EGFP, LSL-Kras(G12D/+), LSL Trp53(R172H/+) mice. However, there was no survival advantage in the dasatinib treated animals owing to continued growth of the primary tumor. CONCLUSIONS: This study confirms the importance of Src in human PDAC and shows the usefulness of a genetically engineered mouse model of PDAC for assessing the activity of potential antimetastatic agents and suggests that dasatinib should be evaluated further as monotherapy after resection of localized invasive PDAC. PMID- 20303351 TI - Dissociation between intrahepatic triglyceride content and insulin resistance in familial hypobetalipoproteinemia. AB - BACKGROUND & AIMS: Hepatic steatosis is associated with insulin resistance, but it is not clear whether increased intrahepatic triglyceride (IHTG) content causes the resistance or is a marker. Subjects with familial hypobetalipoproteinemia (FHBL) have high levels of IHTG because of a genetic defect in hepatic export of triglycerides, and provide a unique cohort to study the relationship between steatosis and insulin sensitivity. METHODS: One group of lean subjects with normal IHTG content (2.2% +/- 0.6% of liver volume) (n = 6), and 3 groups of overweight and obese subjects matched for body mass index, were studied: (1) normal IHTG content (3.3% +/- 0.5%; n = 6), (2) high IHTG content (21.4% +/- 2.6%) due to nonalcoholic fatty liver disease (NAFLD; n = 6), and (3) high IHTG content (18.1% +/- 2.2%) due to FHBL (n = 3). A hyperinsulinemic-euglycemic clamp procedure, in conjunction with glucose tracer infusion, was used to determine multiorgan insulin sensitivity. RESULTS: Hepatic insulin sensitivity (reciprocal of glucose rate of appearance [micromol x kg fat-free mass(-1) x min(-1)] x insulin [mU/L]) was greatest in the Lean group (2.0 +/- 0.4); it was the same among subjects with FHBL (0.8 +/- 0.1) and the group with normal IHTG content, matched for body mass index (0.7 +/- 0.1), but greater than the NAFLD group (0.3 +/- 0.1) (P < .01). Muscle insulin sensitivity (percent increase in glucose uptake during insulin infusion) was greatest in the Lean group (576% +/- 70%). Muscle insulin sensitivity was similar in subjects with FHBL and those with normal IHTG (319% +/- 77%, 326% +/- 27%, respectively), but greater than the NAFLD group (145% +/- 18%) (P < .01). CONCLUSIONS: Steatosis is dissociated from insulin resistance in FHBL, which suggests that increased IHTG content is a marker, not a cause, of metabolic dysfunction. PMID- 20303352 TI - Ribavirin improves early responses to peginterferon through improved interferon signaling. AB - BACKGROUND & AIMS: The therapeutic mechanisms of ribavirin for hepatitis C are unclear. Microarray analyses have shown that ribavirin increases induction of interferon-stimulated genes. We evaluated viral kinetics, serum cytokine expression, and viral mutagenesis during early stages of peginterferon therapy with and without ribavirin. METHODS: Fifty patients with chronic hepatitis C virus (HCV) infection genotype 1 were randomly assigned to groups that were given peginterferon alpha-2a, with or without ribavirin, for 4 weeks; all patients then received an additional 44 weeks of combination therapy. First- and second-phase viral kinetics were evaluated. Serum levels of interferon-gamma-inducible protein 10 (IP10), monokine induced by interferon-gamma, and monocyte chemoattractant protein 1 were quantified as measures of the interferon-stimulated genes response. NS5A and NS5B were partially sequenced, and mutation rates were calculated. RESULTS: The first-phase decrease in HCV RNA was similar between groups. Patients who received ribavirin had a more rapid second-phase decrease, compared with patients who did not receive ribavirin-particularly those with an adequate first-phase decrease (0.61 vs 0.35 log10 IU/mL/week; P = .018). At 12 hours, fold induction of serum IP10 was higher in patients given the combination therapy than those given peginterferon only (7.6- vs 3.8-fold; P = .01); however, the difference was greatest in patients with an adequate first-phase decrease in HCV RNA. IP10-induction correlated with first- and second-phase kinetics and with ribavirin serum concentrations on day 3. HCV mutation rates were similar between groups. CONCLUSIONS: Ribavirin improves the kinetics of the early response to therapy in patients with an adequate initial response to peginterferon. Induction of interferon-stimulated cytokines correlates with viral kinetics following ribavirin therapy, suggesting that ribavirin promotes interferon signaling. PMID- 20303353 TI - Helicobacter pylori CagL activates ADAM17 to induce repression of the gastric H, K-ATPase alpha subunit. AB - BACKGROUND & AIMS: Infection with Helicobacter pylori represses expression of the gastric H, K-adenosine triphosphatase alpha-subunit (HKalpha), which could contribute to transient hypochlorhydria. CagL, a pilus protein component of the H pylori type IV secretion system, binds to the integrin alpha(5)beta1 to mediate translocation of virulence factors into the host cell and initiate signaling. alpha(5)beta1 binds a disintegrin and metalloprotease (ADAM) 17, a metalloenzyme that catalyzes ectodomain shedding of receptor tyrosine kinase ligands. We investigated whether H pylori-induced repression of HKalpha is mediated by CagL activation of ADAM17 and release of heparin-binding epidermal growth factor (HB EGF). METHODS: HKalpha promoter and ADAM17 activity were measured in AGS gastric epithelial cells transfected with HKalpha promoter-reporter constructs or ADAM17 specific small interfering RNAs and infected with H pylori. HB-EGF secretion was measured by enzyme-linked immunosorbent assay analysis, and ADAM17 interaction with integrins was investigated by coimmunoprecipitation analyses. RESULTS: Infection of AGS cells with wild-type H pylori or an H pylori cagL-deficient isogenic mutant that also contained a wild-type version of cagL (P12DeltacagL/cagL) repressed HKalpha promoter-Luc reporter activity and stimulated ADAM17 activity. Both responses were inhibited by point mutations in the nuclear factor-kappaB binding site of HKalpha or by infection with P12DeltacagL. Small interfering RNA-mediated silencing of ADAM17 in AGS cells inhibited the repression of wild-type HKalpha promoter and reduced ADAM17 activity and HB-EGF production, compared to controls. Coimmunoprecipitation studies of AGS lysates showed that wild-type H pylori disrupted ADAM17 alpha5beta1 complexes. CONCLUSIONS: During acute H pylori infection, CagL dissociates ADAM17 from the integrin alpha(5)beta1 and activates ADAM17 dependent, nuclear factor-kappaB-mediated repression of HKalpha. This might contribute to transient hypochlorhydria in patients with H pylori infection. PMID- 20303354 TI - Acid and bile salt-induced CDX2 expression differs in esophageal squamous cells from patients with and without Barrett's esophagus. AB - BACKGROUND & AIMS: It is not clear why only a minority of patients with gastroesophageal reflux disease (GERD) develop Barrett's esophagus. We hypothesized that differences among individuals in molecular pathways activated when esophageal squamous epithelium is exposed to reflux underlie the development of Barrett's metaplasia. METHODS: We used esophageal squamous cell lines from patients who had GERD with Barrett's esophagus (normal esophageal squamous [NES] B3T and NES-B10T) and without Barrett's esophagus (NES-G2T and NES-G4T) to study effects of acid and bile salts on expression of the CDX2 gene. Bay 11-705, Ad5 inhibitor kappaB(IkappaB)alpha-SR, and site-directed mutagenesis were used to explore effects of nuclear factor-kappaB (NF-kappaB) inhibition on CDX2 promoter activity; DNA binding of the NF-kappaB subunits p50 and p65 was assessed by chromatin immune-precipitation. RESULTS: Acid and bile salts increased CDX2 messenger RNA (mRNA), protein, and promoter activity in NES-B3T and NES-B10T cells, but not in NES-G2T or NES-G4T cells. Inhibition of NF-kappaB abolished the increase in CDX2 promoter activity. Increased CDX2 promoter activity was associated with nuclear translocation of p50, which bound to the promoter. We found CDX2 mRNA in 7 of 10 esophageal squamous biopsy specimens from patients with Barrett's esophagus, but in only 1 of 10 such specimens from patients who had GERD without Barrett's esophagus. CONCLUSIONS: Acid and bile salts induce CDX2 mRNA and protein expression in esophageal squamous cells from patients with Barrett's esophagus, but not from GERD patients without Barrett's esophagus. We speculate that these differences in acid- and bile salt-induced activation of molecular pathways may underlie the development of Barrett's metaplasia. PMID- 20303355 TI - Serotonin signaling is altered in irritable bowel syndrome with diarrhea but not in functional dyspepsia in pediatric age patients. AB - BACKGROUND & AIMS: In adults, irritable bowel syndrome (IBS) and functional dyspepsia (FD) are chronic conditions that often start during childhood. We investigated mucosal serotonin (5-HT) signaling in children with the idea that data from subjects with a shorter history may improve our understanding of underlying pathophysiological mechanisms. METHODS: Ninety-eight children undergoing gastroscopy or colonoscopy were studied prospectively. Biopsy specimens were evaluated for inflammation, enterochromaffin cell numbers, 5-HT content, and messenger RNA (mRNA) levels for the synthetic enzyme, tryptophan hydroxylase 1, and the serotonin transporter (SERT) were assessed by quantitative real-time reverse-transcription polymerase chain reaction. RESULTS: Data from 12 children with IBS and 17 with FD were compared with age-matched controls (12 with rectal biopsies and 12 with gastric biopsies) and with subjects with organic disorders. In patients with FD, a small number of immune cells were observed in the gastric mucosa in half of the patients, but no abnormalities with respect to the 5-HT pathway were identified. In patients with IBS, no differences were detected between patients and controls regarding intraepithelial lymphocytes and CD3+ cells in the lamina propria although all patients showed at least a slight inflammatory infiltrate. In the IBS samples, higher 5-HT content (P < .01) and lower SERT mRNA (P < .05) were detected as compared with controls. Severe inflammation in the colonic mucosa had a high impact on 5-HT signaling with a significant decrease in enterochromaffin cells (P < .01) and 5-HT content (P < .01) and a high SERT mRNA expression (P < .01). CONCLUSIONS: These results confirm the role of 5-HT signaling in IBS in children and argue against such a role in FD. PMID- 20303356 TI - Human risk allele HLA-DRB1*0405 predisposes class II transgenic Ab0 NOD mice to autoimmune pancreatitis. AB - BACKGROUND & AIMS: Autoimmune pancreatitis (AIP) underlies 5%-11% of cases of chronic pancreatitis. An association between AIP and the human leukocyte antigen (HLA)-DRB1*0405/DQB1*0401 haplotype has been reported, but linkage disequilibrium has precluded the identification of predisposing HLA gene(s). We studied the role of single HLA genes in the development of AIP in transgenic mice. METHODS: CD4(+) T-cell-negative I-Abeta chain(-/-) (Ab0) mice develop AIP spontaneously, likely due to dysregulation of CD8(+) T- cell responses. We generated Ab0 nonobese diabetic (NOD) mice transgenic for HLA-DR*0405, leading to rescue of CD4(+) T cells; we compared their susceptibility to AIP with HLA-DQ8 or HLA-DR*0401 (single) transgenic, or HLA-DR*0405/DQ8 (double) transgenic mice. RESULTS: CD4(+) T-cell-competent HLA-DR*0405 transgenic Ab0 NOD mice develop AIP with high prevalence after sublethal irradiation and adoptive transfer of CD90(+) T cells, leading to complete pancreatic atrophy. HLA-DR*0405 transgenic mice can also develop unprovoked AIP, whereas HLA-DR*0401, HLA-DQ8, and HLA-DR*0405/DQ8 transgenic Ab0 NOD controls all remained normal, even after irradiation and adoptive transfer of CD90(+) T cells. Pancreas histology in HLA-DR*0405 transgenic mice was characterized by destructive infiltration of the exocrine tissue with CD4(+) and CD8(+) T cells, B cells, and macrophages. Mice with complete pancreatic atrophy lost weight, developed fat stools, and had reduced levels of serum lipase activity. CONCLUSIONS: Because HLA-DR*0405 expression fails to protect mice from AIP, the HLA-DRB1*0405 allele appears to be an important risk factor for AIP on the HLA-DRB1*0405/DQB1*0401 haplotype. This humanized mouse model should be useful for studying immunopathogenesis, diagnostic markers, and therapy of human AIP. PMID- 20303357 TI - Behavioral and physiological plasticity: rapid changes during social ascent in an African cichlid fish. AB - In many vertebrates, reproduction is regulated by social interactions in which dominant males control access to females and food. Subordinate males that displace dominant individuals must rapidly adopt behavioral and physiological traits of the higher rank to gain reproductive success. To understand the process of phenotypic plasticity during social ascent, we analyzed the temporal expression pattern of dominance behaviors and circulating androgen levels when socially-suppressed males of an African cichlid fish Astatotilapia burtoni ascended in status. These experiments tested a prediction of the 'challenge hypothesis' that, during periods of social instability, male androgen levels are higher than during socially stable times. We found that socially and reproductively suppressed males perform territorial and reproductive behaviors within minutes of an opportunity to ascend in status, and that animals switch from initial expression of territorial behaviors to more reproductive behaviors during territory establishment. Following this rapid response, social stability may be achieved within 1-3 days of social ascent. Consistent with predictions of the 'challenge hypothesis', circulating 11-ketotestosterone (11-KT) levels were elevated within 30 min following social opportunity, coincident with increased aggressive behavior. However, territorial behaviors and serum 11-KT levels were then dissociated by 72h after social ascent, suggesting either rapid social stability and/or increased physiological potential for androgen production. This behavioral and physiological plasticity in male A. burtoni suggests that perception of social opportunity triggers a suite of quick changes to facilitate rapid transition towards reproductive success, and reveals important features of social ascent not previously recognized. PMID- 20303358 TI - Innovation in gene regulation: the case of chromatin computation. AB - Chromatin regulation is understood to be one of the fundamental modes of gene regulation in eukaryotic cells. We argue that the basic proteins that determine the chromatin architecture constitute an evolutionary ancient layer of transcriptional regulation common to all three domains of life. We explore phylogenetically, sources of innovation in chromatin regulation, focusing on protein domains related to chromatin structure and function, demonstrating a step wise increase of complexity in chromatin regulation. Building upon the highly conserved use of variants of chromosomal architectural proteins to distinguish chromosomal states, Eukarya secondarily acquired mechanisms for "writing" chemical modifications onto chromatin that constitute persistent signals. The acquisition of reader domains enabled decoding of these complex, signal combinations and a decoupling of the signal from immediate biochemical effects. We show how the coupling of reading and writing, which is most prevalent in crown group Eukarya, could have converted chromatin into a powerful computational device capable of storing and processing more information than pure cis regulatory networks. PMID- 20303359 TI - Pharmacology of the human skin microcirculation. PMID- 20303360 TI - Effect of metallothionein core promoter region polymorphism on cadmium, zinc and copper levels in autopsy kidney tissues from a Turkish population. AB - Metallothioneins (MTs) are metal-binding, low molecular weight proteins and are involved in pathophysiological processes like metabolism of essential metals, metal ion homeostasis and detoxification of heavy metals. Metallothionein expression is induced by various heavy metals especially cadmium, mercury and zinc; MTs suppress toxicity of heavy metals by binding themselves to these metals. The aim of this study was to investigate the association between the -5 A/G metallothionein 2A (MT2A) single nucleotide polymorphism (SNP) and Cd, Zn and Cu levels in the renal cortex from autopsy cases. MT2A core promoter region -5 A/G SNP was analyzed by PCR-RFLP method using 114 autopsy kidney tissues and the genotype frequencies of this polymorphism were found as 87.7% homozygote typical (AA), 11.4% heterozygote (AG) and 0.9% homozygote atypical (GG). In order to assess the Cd, Zn and Cu levels in the same autopsy kidney tissues, a dual atomic absorption spectrophotometer system was used and the average levels of Cd, Zn and Cu were measured as 95.54+/-65.58 microg/g, 181.20+/-87.72 microg/g and 17.14+/ 16.28 microg/g, respectively. As a result, no statistical association was found between the -5 A/G SNP in the MT2A gene and the Zn and Cu levels in the renal cortex (p>0.05), but considerably high accumulation of Cd was monitored for individuals having AG (151.24+/-60.21 microg/g) and GG genotypes (153.09 microg/g) compared with individuals having AA genotype (87.72+/-62.98 microg/g) (p<0.05). These results show that the core promoter region polymorphism of metallothionein 2A increases the accumulation of Cd in human renal cortex. PMID- 20303361 TI - Cardiac cell modelling: observations from the heart of the cardiac physiome project. AB - In this manuscript we review the state of cardiac cell modelling in the context of international initiatives such as the IUPS Physiome and Virtual Physiological Human Projects, which aim to integrate computational models across scales and physics. In particular we focus on the relationship between experimental data and model parameterisation across a range of model types and cellular physiological systems. Finally, in the context of parameter identification and model reuse within the Cardiac Physiome, we suggest some future priority areas for this field. PMID- 20303363 TI - Mechanism-based approaches to treating fragile X. AB - Fragile X is the leading inherited cause of mental retardation and autism. Recent advances in our mechanistic understanding of the disease have led to the identification of the metabotropic glutamate receptor (mGluR) as a therapeutic target for the disease. These studies have revealed that core defects in multiple animal models can be corrected by down regulation of mGluR5 signaling. Although it remains to be seen if mGluR5 antagonists or related approaches will succeed in humans with fragile X, the progress in fragile X stands as a strong testament to the power of applying knowledge of basic neurobiology to understand pathophysiology in a genetically validated model of human psychiatric disease. These breakthroughs and several of the resulting drug development efforts are reviewed. PMID- 20303362 TI - Predictors of reported influenza vaccination in HIV-infected women in the United States, 2006-2007 and 2007-2008 seasons. AB - OBJECTIVE: To estimate the cumulative incidence of self-reported influenza vaccination ("vaccination coverage") and investigate predictors in HIV-infected women. METHODS: In an ongoing cohort study of HIV-infected women in five US cities, data from two influenza seasons (2006-2007 n=1209 and 2007-2008 n=1161) were used to estimate crude and adjusted prevalence ratios (aPR) and 95% confidence intervals ([,]) from Poisson regression with robust variance models using generalized estimating equations (GEE). RESULTS: In our study, 55% and 57% of HIV-infected women reported vaccination during the 2006-2007 and 2007-2008 seasons, respectively. Using data from both seasons, older age, non-smoking status, CD4 T-lymphocyte (CD4) count > or =200 cells/mm(3), and reporting at least one recent healthcare visit was associated with increased vaccination coverage. In the 2007-2008 season, a belief in the protection of the vaccine (aPR=1.38 [1.18, 1.61]) and influenza vaccination in the previous season (aPR=1.66 [1.44, 1.91]) most strongly predicted vaccination status. CONCLUSION: Interventions to reach unvaccinated HIV-infected women should focus on changing beliefs about the effectiveness of influenza vaccination and target younger women, current smokers, those without recent healthcare visits, or a CD4 count <200 cells/mm(3). PMID- 20303364 TI - Morphological correlates of MAO A VNTR polymorphism: new evidence from cortical thickness measurement. AB - A functional variant in the mono-amine oxidase A (MAO A) gene has been shown to impact neural function related to cognitive and affective processing and increase risk for conduct disorders. However, whether MAO A could be a candidate gene for structural variation in the human brain remains to be clarified. This study is the first to investigate the effect of this genotype on brain morphology by measuring cortical thickness. We genotyped 59 healthy male subjects (36 carrying the MAO A High-activity allele and 23 the MAO A Low-activity allele) who underwent structural MRI at 3T. Models of the grey-white and pial surfaces were generated for each individual's cortices, and the distance between these two surfaces was used to compute cortical thickness within a priori regions of interest of the orbitofrontal and cingulate cortices. Surface-based analysis of the cortical mantle showed that the MAO A genotype was associated with structural differences in the orbitofrontal cortex bilaterally, where the MAO A High activity group showed the highest cortical thickness value and the MAO A Low activity group the lowest. Otherwise, no significant difference was detected within the cingulate cortex. Thus, we confirm the hypothesis that the MAO A genotype has a specific impact on human brain morphology. In particular, thickness measurement of the orbitofrontal cortex provides new evidence about the biological impact of the MAO A genotype on neural systems relevant to the pathophysiology of behavioural disorders. PMID- 20303365 TI - Herpesviruses: hijacking the Ras signaling pathway. AB - Cancer is the final result of the accumulation of several genetic alterations occurring in a cell. Several herpesviruses and especially gamma-herpesviruses have played an important role in Cancer Biology, contributing significantly to our comprehension of cell signaling and growth control pathways which lead to malignancy. Unlike other infectious agents, herpesviruses persist in the host by establishing a latent infection, so that they can reactivate periodically. Interestingly, some herpesviruses are able to either deliver or induce the expression of cellular oncogenes. Such alterations can result in the derailment of the normal cell cycle and ultimately shift the balance between continuous proliferation and programmed cell death. Herpesvirus infection employs key molecules of cellular signaling cascades mostly to enhance viral replication. However, most of these molecules are also involved in essential cellular functions, such as proliferation, cellular differentiation and migration, as well as in DNA repair mechanisms. Ras proteins are key molecules that regulate a wide range of cellular functions, including differentiation, proliferation and cell survival. A broad field of medical research is currently focused on elucidating the role of ras oncogenes in human tumor initiation as well as tumor progression and metastasis. Upon activation, Ras proteins employ several downstream effector molecules such as phosphatidylinositol 3-kinase (PI3-K) and Raf and Ral guanine nucleotide-dissociation stimulators (RALGDS) to regulate a cascade of events ranging from cell proliferation and survival to apoptosis and cellular death. In this review, we give an overview of the impact that herpesvirus infection has on the host-cell Ras signaling pathway, providing an outline of their interactions with the key cascade molecules with which they associate. Several of these interactions of viral proteins with member of the Ras signaling pathway may be crucial in determining herpesviruses' oncogenic potential or their oncomodulatory behavior. The questions that emerge concern the potential role of these molecules as therapeutic targets both for viral infections and cancer. Understanding the means by which viruses may cause oncogenesis would therefore provide a deeper knowledge of the overall oncogenic process. PMID- 20303367 TI - A simple but accurate method for histological reconstruction of the large-sized brain tissue of the human that is applicable to construction of digitized brain database. AB - Research on the human brain has undoubted significance, but our knowledge on its detailed morphology is still limited. We have developed a simple method for reconstruction of large-sized brain tissues of the human. Fixed brains were cut into blocks (maximum size 7 cm x 7 cm x 1 cm), embedded and postfixed in gelatin just one overnight before obtaining complete serial sections with a vibrating microtome. Quality of stained materials was sufficient to create three dimensional histological maps, where digital reconstructions from adjoining blocks could be accurately combined. The present method will facilitate both direct examination of the human brain and construction of its histological database. PMID- 20303366 TI - ErbB4 regulates the timely progression of late fetal lung development. AB - The ErbB4 receptor has an important function in fetal lung maturation. Deletion of ErbB4 leads to alveolar hypoplasia and hyperreactive airways similar to the changes in bronchopulmonary dysplasia (BPD). BPD is a chronic pulmonary disorder affecting premature infants as a consequence of lung immaturity, lung damage, and abnormal repair. We hypothesized that proper ErbB4 function is needed for the timely progression of fetal lung development. An ErbB4 transgenic cardiac rescue mouse model was used to study the effect of ErbB4 deletion on fetal lung structure, surfactant protein (SP) expression, and synthesis, and inflammation. Morphometric analyses revealed a delayed structural development with a significant decrease in saccular size at E18 and more pronounced changes at E17, keeping these lungs in the canalicular stage. SP-B mRNA expression was significantly down regulated at E17 with a subsequent decrease in SP-B protein expression at E18. SP-D protein expression was significantly decreased at E18. Surfactant phospholipid synthesis was significantly decreased on both days, and secretion was down regulated at E18. We conclude that pulmonary ErbB4 deletion results in a structural and functional delay in fetal lung development, indicating a crucial regulatory role of ErbB4 in the timely progression of fetal lung development. PMID- 20303368 TI - Beta-alanyl peptide synthesis by Streptomyces S9 aminopeptidase. AB - Synthesis of beta-alanine (beta-Ala) containing dipeptide using S9 aminopeptidase from Streptomyces thermocyaneoviolaceus NBRC14271 (S9AP-St) was demonstrated with beta-Ala-benzyl ester (-OBzl) and various L-aminoacyl derivatives. For synthesis of beta-Ala-containing dipeptide, beta-Ala-OBzl was used preferentially as the acyl donor for S9AP-St, producing synthesized dipeptides having beta-Ala-Xaa structure. In contrast, engineering of S9AP-St into "transaminopeptidase" by substitution of catalytic Ser with Cys--designated as aminolysin-S--produced only dipeptides having Xaa-beta-Ala structure. Investigation of the specificity of S9AP-St toward acyl acceptors showed that S9AP has a broad substrate specificity toward various aminoacyl derivatives. Furthermore, S9AP-St produced carnosine methyl ester (-OMe) with a conversion ratio of beta-Ala-OBzl to carnosine-OMe that was greater than 30%. PMID- 20303369 TI - CASOP: a computational approach for strain optimization aiming at high productivity. AB - The identification of suitable intervention strategies increasing the productivity of microorganisms is a central issue in metabolic engineering. Here, we introduce a computational framework for strain optimization based on reaction importance measures derived from weighted elementary modes. The objective is to shift the natural flux distribution to synthesis of the desired product with high production rates thereby retaining the ability of the host organism to produce biomass precursors. The stoichiometric approach allows consideration of regulatory/operational constraints and takes product yield and network capacity- the two major determinants of (specific) productivity--explicitly into account. The relative contribution of each reaction to yield and network capacity and thus productivity is estimated by analyzing the spectrum of available conversion routes (elementary modes). A result of our procedure is a reaction ranking suggesting knockout and overexpression candidates. Moreover, we show that the methodology allows for the evaluation of cofactor and co-metabolite requirements in conjunction with product synthesis. We illustrate the proposed method by studying the overproduction of succinate and lactate by Escherichia coli. The metabolic engineering strategies identified in silico resemble existing mutant strains designed for the synthesis of the respective products. Additionally, some non-intuitive intervention strategies are revealed. PMID- 20303370 TI - Inhibition of hepatitis B virus replication by the internal fragment of hepatitis B core protein. AB - The nucleocapsids formation is a pivotal step of hepatitis B virus (HBV) life cycle. The inhibition of HBV nucleocapsids assembly is a promising strategy for the anti-HBV treatment. HBc78-117 is an internal fragment of hepatitis B core protein (HBc). In this study, we used lentiviral vector to deliver HBc78-117 cDNA sequence into HepG2.2.15 cells and examined the effect of HBc78-117 on HBV replication. We confirmed by immunoprecipitation analysis that HBc78-117 interacted with full-length HBc in HepG2.2.15 cells. The nucleocapsids and HBV DNA replication intermediates were markedly reduced in the cells expressing HBc78 117, although HBV pregenome RNA was not affected. The level of HBV DNA was also significantly reduced in culture supernatant. These suggest that HBc78-117 can inhibit HBV DNA replication by interfering with nucleocapsids assembly. PMID- 20303371 TI - Effects of stevia, aspartame, and sucrose on food intake, satiety, and postprandial glucose and insulin levels. AB - Consumption of sugar-sweetened beverages may be one of the dietary causes of metabolic disorders, such as obesity. Therefore, substituting sugar with low calorie sweeteners may be an efficacious weight management strategy. We tested the effect of preloads containing stevia, aspartame, or sucrose on food intake, satiety, and postprandial glucose and insulin levels. DESIGN: 19 healthy lean (BMI=20.0-24.9) and 12 obese (BMI=30.0-39.9) individuals 18-50 years old completed three separate food test days during which they received preloads containing stevia (290kcal), aspartame (290kcal), or sucrose (493kcal) before the lunch and dinner meal. The preload order was balanced, and food intake (kcal) was directly calculated. Hunger and satiety levels were reported before and after meals, and every hour throughout the afternoon. Participants provided blood samples immediately before and 20min after the lunch preload. Despite the caloric difference in preloads (290kcal vs. 493kcal), participants did not compensate by eating more at their lunch and dinner meals when they consumed stevia and aspartame versus sucrose in preloads (mean differences in food intake over entire day between sucrose and stevia=301kcal, p<.01; aspartame=330kcal, p<.01). Self reported hunger and satiety levels did not differ by condition. Stevia preloads significantly reduced postprandial glucose levels compared to sucrose preloads (p<.01), and postprandial insulin levels compared to both aspartame and sucrose preloads (p<.05). When consuming stevia and aspartame preloads, participants did not compensate by eating more at either their lunch or dinner meal and reported similar levels of satiety compared to when they consumed the higher calorie sucrose preload. PMID- 20303372 TI - Matrix metalloproteinase-9 activity increased by two different types of epileptic seizures that do not induce neuronal death: a possible role in homeostatic synaptic plasticity. AB - Matrix metalloproteases (MMPs) degrade or modify extracellular matrix or membrane bound proteins in the brain. MMP-2 and MMP-9 are activated by treatments that result in a sustained neuronal depolarization and are thought to contribute to neuronal death and structural remodeling. At the synapse, MMP actions on extracellular proteins contribute to changes in synaptic efficacy during learning paradigms. They are also activated during epileptic seizures, and MMP-9 has been associated with the establishment of aberrant synaptic connections after neuronal death induced by kainate treatment. It remains unclear whether MMPs are activated by epileptic activities that do not induce cell death. Here we examine this point in two animal models of epilepsy that do not involve extensive cell damage. We detected an elevation of MMP-9 enzymatic activity in cortical regions of secondary generalization after focal seizures induced by 4-aminopyridine (4-AP) application in rats. Pro-MMP-9 levels were also higher in Wistar Glaxo Rijswijk (WAG/Rij) rats, a genetic model of generalized absence epilepsy, than they were in Sprague-Dawley rats, and this elevation was correlated with diurnally occurring spike-wave-discharges in WAG/Rij rats. The increased enzymatic activity of MMP-9 in these two different epilepsy models is associated with synchronized neuronal activity that does not induce widespread cell death. In these epilepsy models MMP-9 induction may therefore be associated with functions such as homeostatic synaptic plasticity rather than neuronal death. PMID- 20303373 TI - Association analysis of myosin IXB and type 1 diabetes. AB - To date, seven studies have provided evidence for an association between the gene encoding for myosin IXB (MYO9B) and celiac disease (CD), and inflammatory bowel diseases, including single nucleotide polymorphisms (SNPs) rs2305767, rs1457092, and rs2305764. We investigated whether MYO9B is associated with T1D. The three SNPs were genotyped in Dutch samples from 288 T1D patients and 1615 controls. The A allele of SNP rs2305767A>G showed some evidence of association with T1D (nominal p for genotype = 0.06; OR carrier = 1.51, 95% CI = 1.04-2.19), but not in British samples from 4301 case patients and 4706 controls (p = 0.53), or when the Dutch and UK data were pooled (N patients = 4582, N controls= 6224; Mantel Hansel p = 0.83). Furthermore, the nonsynonymous rs1545620 C>A SNP that has been associated with the inflammatory bowel disease, showed no association with T1D in British case-control set (p = 0.57). We conclude that MYO9B might not be a strong determinant of T1D, although there was some association in our initial Dutch study. Further studies are needed to evaluate the role of MYO9B in T1D. PMID- 20303374 TI - Estimation of nicotine and tar yields from human-smoked cigarettes before and after the implementation of the cigarette ignition propensity regulations in Canada. AB - In 2005, Human-Smoked (HS) tar and nicotine yields from commercial Canadian cigarettes were determined using a part filter analysis method to obtain estimates representative of human smoking behavior. In 2006, new cigarette designs were introduced to ensure compliance with the Canadian Low Ignition Propensity (LIP) regulations. It was not known how the changes in product design would affect HS yields. To assess the impact of the cigarette design modifications on HS yields, a further group of Canadian smokers was recruited for smoking the modified version of 10 products previously assessed. No differences in estimated HS tar yields were found between products following product modification. The HS nicotine yield was different for one product. In general, HS yields were higher than ISO machine yields while Canadian intense machine yields were more representative of the maximum HS yields. The same product ranking order was obtained for HS yields and the two machine yields but differences between the mean HS yields and ISO yields were smaller as the product ISO yields increased. Higher HS yields were measured when products were smoked by male smokers. The methodology used in this study showed the wide range of HS yields obtained by smokers as well as a good degree of stability in average HS yields just before and after the introduction of LIP regulations. PMID- 20303376 TI - Derivation of a reference dose and drinking water equivalent level for 1,2,3 trichloropropane. AB - In some US potable water supplies, 1,2,3-trichloropropane (TCP) has been present at ranges of non-detect to less than 100 ppb, resulting from past uses. In subchronic oral studies, TCP produced toxicity in kidneys, liver, and other tissues. TCP administered by corn oil gavage in chronic studies produced tumors at multiple sites in rats and mice; however, interpretation of these studies was impeded by substantial premature mortality. Drinking water equivalent levels (DWELs) were estimated for a lifetime of consumption by applying biologically based safety/risk assessment approaches, including Monte Carlo techniques, and with consideration of kinetics and modes of action, to possibly replace default assumptions. Internationally recognized Frameworks for human relevance of animal data were employed to interpret the findings. Calculated were a reference dose (=39 microg/kg d) for non-cancer and Cancer Values (CV) (=10-14 microg/kg d) based on non-linear dose-response relationships for mutagenicity as a precursor of cancer. Lifetime Average Daily Intakes (LADI) are 3130 and 790-1120 microg/person-d for non-cancer and cancer, respectively. DWELs, estimated by applying a relative source contribution (RSC) of 50% to the LADIs, are 780 and 200-280 microg/L for non-cancer and cancer, respectively. These DWELs may inform establishment of formal/informal guidelines and standards to protect public health. PMID- 20303375 TI - Food allergy: stakeholder perspectives on acceptable risk. AB - We have reached a point where it is difficult to improve food allergy risk management without an agreement on levels of acceptable risk. This paper presents and discusses the perspectives of the different stakeholders (allergic consumers, health professionals, public authorities and the food industry) on acceptable risk in food allergy. Understanding where these perspectives diverge and even conflict may help develop an approach to define what is acceptable. Uncertainty about food allergy, its consequences and how to manage them is the common denominator of the stakeholders' views. In patients, uncertainty is caused by the unpredictability of reactions and the concern about whether avoidance strategies will be effective enough. Variability of symptoms and the lack of markers do not allow stratification of patients according to their reactivity, and force health professionals to give the same advice to all patients despite the fact that the risk to each is not identical. Regulators and the food industry struggle with the fact that the lack of management thresholds forces them to make case-by-case decisions in an area of uncertainty with penalties for under- or over-prediction. As zero risk is not a realistic possibility, consensus on acceptable risk will be needed. PMID- 20303377 TI - Genotoxic and antimutagenic activities of extracts from pseudocereals in the Salmonella mutagenicity assay. AB - Extracts of amaranth (Amaranthus L.), sorghum (Sorghum bicolor L.) and Japanese millet (Echinochloa frumentacea L.) were evaluated for mutagenicity in Salmonella typhimurium strains TA98, TA100 and TA102. All three pseudocereal extracts were also assessed for their antimutagenic properties against the direct mutagens 2 nitrofluorene (2NF) for strain TA98, 3-(5-nitro-2-furyl)acrylic acid (5NFAA) for TA100 and H(2)O(2) for TA102 strain and against the indirect mutagen aflatoxin B(1) (AFB(1)). No mutagenicity was induced by any of the pseudocereal extracts when tested at concentrations as high as 50mg/ml. All three extracts showed similar antimutagenicity against 5NFAA and no antimutagenicity against 2NF. The number of revertants induced by H(2)O(2) extract was inhibited in order amaranth>Japanese milet>sorghum. All extracts were effective in the inhibition of mutagenic activity of aflatoxin B(1). The total polyphenol content as well as the amount of the flavonoids and phenolic acids as main component of polyphenolics were also determined. PMID- 20303378 TI - Humor attenuates the cortisol awakening response in healthy older men. AB - This study examined the impact of an important factor contributing to successful aging, humor, on post-awakening cortisol levels among a group of 45 older men whose ages ranged from 64 years to 86 years (mean=73.6 years). Four saliva samples were collected from the participants for 2 days immediately after waking and every 15 min thereafter for three times. Cortisol data of the 2 days were aggregated for analysis. Two separate indices of cortisol awakening response reflecting the mean level of secretion and the rise from immediately to 45 min post-awakening, AUC(G) and AUC(I), were computed using the trapezoid formula. The relation of these two indices to humor (operationalized as coping) was examined in a multiple regression analysis while controlling for the effect of age, socioeconomic status, and self-esteem. Results indicated that higher humor scores were associated with lower AUC(G) but had no relation with AUC(I). Findings of the present study suggest that the hypothalamic-pituitary-adrenocortical axis is the major pathway whereby positive psychological dispositions, such as humor, exert their health effects in the aging population. Moreover, cortisol levels in the awakening period may be particularly sensitive to the influences of psychosocial factors. PMID- 20303379 TI - Platelet-activating factor and acute myelogenous leukemia. PMID- 20303380 TI - Dynamic regulation of Gata1 expression during the maturation of conventional dendritic cells. AB - OBJECTIVES: To identify the regulatory sequences driving Gata1 expression in conventional dendritic cells (cDC). MATERIALS AND METHODS: The number and expression levels of Gata1, Gata1-target genes and hypersensitive site (HS) 2 (the eosinophil-specific enhancer)-driven green fluorescent protein (GFP) reporter of cDCs from mice lacking HS1 (the erythroid/megakaryocytic-specific enhancer, Gata1(low) mutation) and wild-type littermates, as well as the response to lipopolysaccharide of ex vivo-generated wild-type and Gata1(low) DCs were investigated. RESULTS: cDC maturation was associated with bell-shaped changes in Gata1 expression that peaked in cDCs precursors from blood. The Gata1(low) mutation did not affect Gata1 expression in cDC precursors and these cells expressed the HS2-driven reporter, indicating that Gata1 expression is HS2-driven in these cells. By contrast, the Gata1(low) mutation reduced Gata1 expression in mature cDCs and these cells did not express GFP, indicating that mature cDCs express Gata1 driven by HS1. In blood, the number of cDC precursors expressing CD40/CD80 was reduced in Gata1(low) mice, while CD40(pos)/CD80(pos) cDC precursors from wild-type mice expressed the HS2-GFP reporter, suggesting that Gata1 expression in these cells is both HS1- and HS2-driven. In addition, the antigen and accessory molecules presentation process induced by lipopolysaccharide in ex vivo-generated wild-type DC was associated with increased acetylated histone 4 occupancy of HS1, while ex vivo-generated Gata1(low) cDCs failed to respond to lipopolysaccharide, suggesting that HS1 activation is required for cDC maturation. CONCLUSION: These results identify a dynamic pattern of Gata1 regulation that switches from an HS1 to an HS2-dependent phase during the maturation of cDCs associated with the antigen-presentation process in the blood. PMID- 20303382 TI - Fibrocytes in health and disease. AB - Fibrocytes are circulating mesenchymal progenitor cells that participate in tissue responses to injury and invasion. Accumulating knowledge from animal models regarding the differentiation, trafficking, and function of these cells implicates them in the development of diseases characterized by chronic inflammation and excessive collagen deposition. Recent data obtained from the clinical setting suggests that the enumeration of circulating fibrocytes may be a biomarker for disease progression in chronic lung diseases including asthma and pulmonary fibrosis. A greater understanding of the immunologic mediators that influence fibrocyte biology suggests new opportunities for therapeutic manipulation of these cells in fibrogenesis. This review integrates new developments in the cellular and molecular biology of fibrocytes with current concepts regarding the etiopathogenesis of fibrosing disorders. PMID- 20303383 TI - Design of Ad5F35 vectors for coordinated dual gene expression in candidate human hematopoietic stem cells. AB - OBJECTIVE: Adenoviral vector-mediated gene expression is an attractive approach to manipulate or report gene expression in human hematopoietic stem cells (HSC) when transient gene expression is preferred. Previous studies have demonstrated that fiber-retargeted Ad5F35 vectors can mediate efficient gene transfer into human HSCs. In this study, we investigated the potential of bi-directional promoter-controlled Ad5F35 vector for coordinated dual gene expression in candidate HSCs. MATERIALS AND METHODS: We have engineered Ad5F35-DeltaLNGFR-BiDp encoding kinase domain deleted low-affinity NGF receptor (DeltaLNGFR) and green fluorescent protein (GFP) expression cassette controlled by a synthetic bi directional promoter, which is composed of human phosphoglycerate kinase promoter and minimal core promoter from human cytomegalovirus. The expression pattern of DeltaLNGFR and GFP following Ad5F35-DeltaLNGFR-BiDp gene transfer in various cell types, including candidate HSCs, was compared to Ad5F35-DeltaLNGFR-IRES vector encoding phosphoglycerate kinase promoter-controlled bicistronic expression cassette for DeltaLNGFR and GFP. RESULTS: Using Ad5F35-DeltaLNGFR-BiDp, we demonstrated a coordinated, high-level dual gene expression in leukemic cells and cord blood CD34(+) cells. However, the ability of Ad5F35-DeltaLNGFR-BiDp-GFP for coordinated dual gene expression varied significantly between repopulating progenitor cells. In nonobese diabetic severe combined immune deficient mice bone marrow transplantation assay, sorted CD34(+)/DeltaLNGFR(+)/GFP(+) cells following infection with Ad5F35-DeltaLNGFR-BiDp showed predominantly myeloid lineage reconstitution with limited lymphoid lineage differentiation capacity, whereas the CD34(+)/DeltaLNGFR(+)/GFP(-) cells exhibited both myeloid and lymphoid reconstitution. CONCLUSIONS: This study indicates that bi-directional promoter controlled Ad5F35 vector, such as Ad5F35-DeltaLNGFR-BiDp, can be particularly useful for manipulation of myeloid progenitor cells and potentially in myeloid lineage leukemic cells as well. PMID- 20303385 TI - DNA-based random number generation in security circuitry. AB - DNA-based circuit design is an area of research in which traditional silicon based technologies are replaced by naturally occurring phenomena taken from biochemistry and molecular biology. This research focuses on further developing DNA-based methodologies to mimic digital data manipulation. While exhibiting fundamental principles, this work was done in conjunction with the vision that DNA-based circuitry, when the technology matures, will form the basis for a tamper-proof security module, revolutionizing the meaning and concept of tamper proofing and possibly preventing it altogether based on accurate scientific observations. A paramount part of such a solution would be self-generation of random numbers. A novel prototype schema employs solid phase synthesis of oligonucleotides for random construction of DNA sequences; temporary storage and retrieval is achieved through plasmid vectors. A discussion of how to evaluate sequence randomness is included, as well as how these techniques are applied to a simulation of the random number generation circuitry. Simulation results show generated sequences successfully pass three selected NIST random number generation tests specified for security applications. PMID- 20303384 TI - Interferon-alpha targets JAK2V617F-positive hematopoietic progenitor cells and acts through the p38 MAPK pathway. AB - OBJECTIVE: Interferon-alpha (IFNalpha) therapy leads to hematological remissions and a reduction of the JAK2V617F allele burden in patients with polycythemia vera (PV). In this study, the cellular target by which IFNalpha affects hematopoiesis in PV patients was evaluated. MATERIALS AND METHODS: CD34(+) cells were isolated from normal bone marrow and the peripheral blood of patients with PV and were treated in vitro with each of the three commercially available forms of IFNalpha: IFNalpha 2b, pegylated IFNalpha 2a (Peg-IFNalpha 2a), and pegylated IFNalpha 2b (Peg-IFNalpha 2b). RESULTS: Each form of IFNalpha was equally potent in suppressing hematopoietic colony formation by normal CD34(+) cells, but Peg IFNalpha 2a and IFNalpha 2b were more effective than Peg-IFNalpha 2b in inhibiting burst-forming unit erythroid-derived colony formation by PV CD34(+) cells. In addition, exposure of PV CD34(+) cells to equal doses of Peg-IFNalpha 2a and IFNalpha 2b resulted in a 38% to 40% reduction in the proportion of JAK2V617F-positive hematopoietic progenitor cells (HPC), while equivalent doses of Peg-IFNalpha 2b did not reduce the number of malignant HPC. Further studies explored the mechanism by which IFNalpha induced PV HPC growth inhibition. Treatment of Peg-IFNalpha 2a increased the rate of apoptosis of PV CD34(+) cells and the phosphorylation/activation of p38 mitogen-activated protein kinase in PV CD34(+) cells, while the p38-specific inhibitor SB203580 reversed the growth inhibition and apoptosis induced by Peg-IFNalpha 2a. CONCLUSION: These data suggest that low doses of IFNalpha selectively and directly suppress PV JAK2V617F HPC and that these agents act through the p38 mitogen-activated protein kinase pathway. PMID- 20303386 TI - Kupffer-cell activity is essential for thyroid hormone rat liver preconditioning. AB - We studied the role of Kupffer cell functioning in T3 liver preconditioning against ischemia-reperfusion (IR) injury using the macrophage inactivator gadolinium chloride (GdCl3) previous to T3 treatment. Male Sprague-Dawley rats given a single i.p. dose of 0.1 mg T3/kg were subjected to 1 h ischemia followed by 20 h reperfusion, in groups of animals pretreated with 10 mg GdCl3/kg i.v. 72 h before T(3) or with the respective vehicles. IR resulted in significant enhancement of serum aspartate aminotransferase (3.3-fold increase) and tumor necrosis factor-alpha (93% increase) levels, development of liver damage, and diminished nuclear factor-kappaB DNA binding over control values. These changes, which were suppressed by the T3 administration prior to IR, persisted in animals given GdCl3 before T3 treatment, under conditions of complete elimination of ED2+ Kupffer cells achieved in a time window of 72 h. It is concluded that Kupffer cell functioning is essential for T3 liver preconditioning, assessed in a warm IR injury model by hepatic macrophage inactivation. PMID- 20303387 TI - Clinical application and consequences of molecular genetics of thyroid diseases. PMID- 20303388 TI - Oxytocin receptor (OXTR) does not play a major role in the aetiology of autism: genetic and molecular studies. AB - Oxytocin (OXT) has been hypothesized to play a role in aetiology of autism based on a demonstrated involvement in the regulation of social behaviours. It is postulated that OXT reduces activation of the amygdala, inhibiting social anxiety, indicating a neural mechanism for the effects of OXT in social cognition. Genetic variation at the oxytocin receptor gene (OXTR) has been reported to be associated with autism. We examined 18 SNPs at the OXTR gene for association in three independent autism samples from Ireland, Portugal and the United Kingdom. We investigated cis-acting genetic effects on OXTR expression in lymphocytes and amygdala region of the brain using an allelic expression imbalance (AEI) assay and by investigating the correlation between RNA levels and genotype in the amygdala region. No marker survived multiple correction for association with autism in any sample or in a combined sample (n=436). Results from the AEI assay performed in the lymphoblast cell lines highlighted two SNPs associated with relative allelic abundance in OXTR (rs237897 and rs237895). Two SNPs were found to be effecting cis-acting variation through AEI in the amygdala. One was weakly correlated with total gene expression (rs13316193) and the other was highlighted in the lymphoblast cell lines (rs237895). Data presented here does not support the role of common genetic variation in OXTR in the aetiology of autism spectrum disorders in Caucasian samples. PMID- 20303389 TI - Effects of moderate exercise on cigarette smoke exposure-induced hippocampal oxidative stress values and neurological behaviors in mice. AB - The objective of the present study was to investigate the effects of exercise training on behavior and neurochemical parameters in mice exposed to cigarette smoke. To this aim, mice (C57 BL6) male (30-35 g) were exposed to cigarette smoke 60 consecutive days three times a day and they were subjected to treadmill training 8 weeks for 5 days/week. For behavior assessment, mice were tested in the open-field and forced to a swim test. The superoxide anion, thiobarbituric acid reactive substances and protein carbonyl formation were measured as markers of oxidative stress in hippocampus of mice. In addition, the brain-derived neurotrophic factor (BDNF) levels were measured in the hippocampus samples. Cigarette smoke group and cigarette smoke plus exercise group, increased immobility time in forced swimming test in rats compared to the control group, without affecting spontaneous locomotor activity. There was an increase in the levels of superoxide, TBARS and of protein carbonyl and a decreased in BDNF levels in the hippocampus of rats exposed to cigarette smoke and cigarette smoke plus exercise. Exercise alone did not change any of the parameters evaluated in this study. In conclusion, we observed that physical training improves the oxidative stress parameters, but does not alter depressive-like behavior neither prevent the decreases in BDNF levels in hippocampus induced by cigarette smoke. PMID- 20303390 TI - Electrophysiological characteristics of identified kidney-related neurons in adult rat spinal cord slices. AB - Whole-cell patch-clamp recordings were made from kidney-related neurons in the intermediolateral cell column (IML) in horizontal slices of thoracolumbar spinal cord from adult rats. Kidney-related neurons were identified in vitro subsequent to inoculation of the kidney with a fluorescent, retrograde, transynaptic pseudorabies viral label (i.e., PRV-152). Kidney-related neurons detected in the IML expressed choline acetyltransferase, characteristic of spinal preganglionic motor neurons. Their mean resting potential was -51+/-4 mV and input resistance was 448+/-39 MOmega. Both spontaneous inhibitory and excitatory post-synaptic currents (i.e., sIPSCs and sEPSCs) were observed in all neurons. The mean frequency for sEPSCs (3.1+/-1 Hz) was approximately 2.5 times that for sIPSCs (1.4+/-0.3 Hz). Application of the glycine and GABA(A) receptor-linked Cl(-) channel blocker, picrotoxin (100 microM) blocked sIPSCs, while the ionotropic glutamate receptor antagonist, kynurenic acid (1 mM) blocked all sEPSCs, indicating they were mediated by GABA/glycine and glutamate receptors, respectively. Thus, using PRV-152 labeling allowed whole-cell patch-clamp recording of neurons in the adult spinal cord, which were kidney-related. Excitatory glutamatergic input dominated synaptic responses in these cells, the membrane characteristics of which resembled those of immature IML neurons. Combined PRV-152 pre-labeling and whole-cell patch-clamp recordings may allow more effective analysis of synaptic plasticity seen in adult models of injury or chronic disease. PMID- 20303391 TI - Changes of AMPA receptors in MPTP monkeys with levodopa-induced dyskinesias. AB - Overactivity of glutamate neurotransmission is suspected to be implicated in Parkinson's disease and levodopa-induced dyskinesia. The fast glutamatergic transmission in the striatum from the cortex is mediated mainly by non-n-methyl-d aspartate (non-NMDA) receptors. Animal models of Parkinson's disease reveal conflicting data concerning striatal glutamate AMPA receptors. The present study thus sought to shed light on the relationship of striatal AMPA receptors to the development of levodopa-induced dyskinesia. [(3)H]Ro 48-8587, a highly potent and selective-specific antagonist ligand for AMPA receptors, was used to investigate, by autoradiography, striatal AMPA receptors in 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine (MPTP)-lesioned monkeys treated for 1 month with levodopa alone, levodopa+CI-1041 (NMDA receptor antagonist) or levodopa+cabergoline (D2 receptor agonist). Levodopa-treated MPTP monkeys developed dyskinesias while those that received levodopa+CI-1041 or levodopa+cabergoline did not. In the anterior caudate nucleus and putamen, specific binding of [(3)H]Ro 48-8587 was reduced in all MPTP-treated monkeys compared to control monkeys, but no significant effect of MPTP was measured in the posterior striatum. In dyskinetic monkeys, specific binding of [(3)H]Ro 48-8587 was elevated in subregions of the posterior caudate nucleus and putamen as compared to saline-treated MPTP monkeys. Levodopa+CI-1041 treatment left unchanged specific binding of [(3)H]Ro 48-8587 whereas levodopa+cabergoline treatment reduced it in subregions of the posterior caudate nucleus and putamen compared to control and levodopa-treated MPTP monkeys. Specific binding of [(3)H]Ro 48-8587 was low in the globus pallidus and remained unchanged following both lesion and treatments. In conclusion, the elevated values of AMPA receptors in dyskinetic monkeys (and their prevention through treatments) were only observed in subregions of the striatum. PMID- 20303392 TI - Verbal memory retrieval engages visual cortex in musicians. AB - As one major line of research on brain plasticity, many imaging studies have been conducted to identify the functional and structural reorganization associated with musical expertise. Based on previous behavioral research, the present study used functional magnetic resonance imaging to identify the neural correlates of superior verbal memory performance in musicians. Participants with and without musical training performed a verbal memory task to first encode a list of words auditorily delivered and then silently recall as many words as possible. They performed in separate blocks a control task involving pure tone pitch judgment. Post-scan recognition test showed better memory performance in musicians than non musicians. During memory retrieval, the musicians showed significantly greater activations in bilateral though left-lateralized visual cortex relative to the pitch judgment baseline. In comparison, no such visual cortical activations were found in the non-musicians. No group differences were observed during the encoding stage. The results echo a previous report of visual cortical activation during verbal memory retrieval in the absence of any visual sensory stimulation in the blind population, who are also known to possess superior verbal memory. It is suggested that the visual cortex can be recruited to serve as extra memory resources and contributes to the superior verbal memory in special situations. While in the blind population, such cross-modal functional reorganization may be induced by sensory deprivation; in the musicians it may be induced by the long term and demanding nature of musical training to use as much available neural resources as possible. PMID- 20303393 TI - Distribution of optokinetic sensitivity across the retina of mice in relation to eye orientation. AB - We examined the effects of stimulus size and location on the mouse optokinetic response (OKR). To this end, we recorded initial OKRs elicited by a brief presentation of horizontally moving grating patterns of different vertical widths and locations in the visual field. Large-field stimuli generated large sustained OKRs, whereas visual stimuli of narrower vertical widths elicited weaker sustained responses at the later period (400-500 ms after the onset of stimulus motion). However, even stimuli of only 5 degrees vertical width elicited detectable transient responses at the initial open-loop period (100-200 ms after the onset of stimulus motion). Presenting 5 degrees -width stimuli at different vertical locations (-10 degrees to +35 degrees relative to the horizon) revealed the spatial distribution of optokinetic sensitivity across the retina. The most sensitive part of the visual field was located at +25 degrees . In addition, we examined the vertical orientation of the eye under our stereotaxic set-up. We observed the optic disc using a hand-held fundus camera and determined the ocular orientation. All eye orientations were distributed in the range of +20-30 degrees relative to the horizon (25.2+/-2.5 degrees ). Thus, the direction of the most sensitive visual field matched the angle of eye orientation. These findings indicate that the spatial distribution of visual field sensitivity to optokinetic stimuli coincides with the distribution of retinal ganglion cell density. PMID- 20303395 TI - Expressions of 5-HT/5-HT(2A) receptors and phospho-protein kinase C theta in the pre-Botzinger complex in normal and chronic intermittent hypoxic rats. AB - The pre-Botzinger complex (pre-BotC), a functionally defined subregion in the ventrolateral medulla oblongata, is a presumed kernel of normal respiratory rhythmogenesis. However, less is known about the pre-BotC's contribution to respiratory neuroplasticity. The most frequently studied model for respiratory neuroplasticity is episodic hypoxia-induced phrenic long-term facilitation, which is 5-HT(2A) receptors (5-HT(2A)R)-dependent. We hypothesized that preconditioning with chronic intermittent hypoxic (CIH) would activate the 5-HT/5-HT(2A)R system and the downstream protein kinase C (PKC) pathway in the pre-BotC. Animals were exposed to alternating 5 min of hypobaric hypoxia and 5 min of normoxia for 10 h/day for 7 days. Hypobaric hypoxia was achieved by continuous air evacuation to reach a pressure of 210-220 mm Hg, corresponding to an altitude of 9000-10000 m. In contrast to the CIH model, a group of animals were pretreated with chronic sustaining hypoxia (CSH), a protocol of continuous hypobaric hypoxia at 360 mm Hg, corresponding to an altitude of about 6000 m, for 10 h/day for 7 days. Immunoreactivity of 5-HT and 5-HT(2A)R was examined in the pre-BotC, identified by the presence of neurokinin-1 receptor (NK1R). We found that 15.5% of 5-HT immunoreactive (ir) terminals were in contact with NK1R-ir neurons. Asymmetric synapses could be identified between them. 38.7% of NK1R-ir dendrites were also immunoreactive for 5-HT(2A)R, which was distributed along the inner surface of the plasma membrane in control animals. CIH challenge increased the expressions of 5-HT and 5-HT(2A)R in the pre-BotC, an increase in the expressed 5-HT(2A)R that was not detected in this region in CSH animals. Specifically, 5-HT(2A)R was distributed not only along the inner surface, but also along the outer surface, or directly on the plasma membrane, a pattern not detectable in control animals. 5-HT(2A)R was also detectable in the invaginations of the plasma membrane, where receptor endocytosis or exocytosis might occur, indicating CIH-induced higher trafficking of 5-HT(2A)R. Concurrently, there was an up-regulation of phospho-PKC theta (P-PKCtheta) in the pre-BotC, suggesting a 5-HT/5-HT(2A)R-activated PKC mechanism that may contribute to hypoxia-induced respiratory neuroplasticity in the pre-BotC. The close association of P-PKCtheta with the postsynaptic density implicates a postsynaptic mechanism mediating respiratory neuroplasticity in the pre-BotC. PMID- 20303394 TI - Differential effects of exercise and dietary docosahexaenoic acid on molecular systems associated with control of allostasis in the hypothalamus and hippocampus. AB - Given the robust influence of diet and exercise on brain plasticity and disease, we conducted studies to determine their effects on molecular systems important for control of brain homeostasis. Studies were centered on a battery of proteins implicated in metabolic homeostasis that have the potential to modulate brain plasticity and cognitive function, in rat hypothalamus and hippocampus. Adult male rats were exposed to a docosahexaenoic acid (DHA) enriched diet (1.25% DHA) with or without voluntary exercise for 14 days. Here we report that the DHA diet and exercise influence protein levels of molecular systems important for the control of energy metabolism (primarily phospho-AMPK, silent information regulator type 1), food intake (primarily leptin and ghrelin receptors), stress (primarily glucocorticoid receptors), and 11beta-hydroxysteroid dehydrogenase 1 (11betaHSD1). Exercise or DHA dietary supplementation had differential effects on several of these class proteins, and the concurrent application of both altered the pattern of response elicited by the single applications of diet or exercise. For example, exercise elevated levels of glucocorticoids receptors in the hypothalamus and the DHA diet had opposite effects, while the concurrent application of diet and exercise suppressed the single effects of diet or exercise. In most of the cases, the hypothalamus and the hippocampus had a distinctive pattern of response to the diet or exercise. The results harmonize with the concept that exercise and dietary DHA exert specific actions on the hypothalamus and hippocampus, with implications for the regulations of brain plasticity and cognitive function. PMID- 20303397 TI - Group-movement 'initiation' and state-dependent decision-making. PMID- 20303396 TI - Two populations of neurokinin 1 receptor-expressing projection neurons in lamina I of the rat spinal cord that differ in AMPA receptor subunit composition and density of excitatory synaptic input. AB - Lamina I of the spinal cord contains many projection neurons that express the neurokinin 1 receptor (NK1r). It has been reported that these cells can undergo long-term potentiation (LTP), which may result from insertion of AMPA-type glutamate receptors (AMPArs) containing GluA1 or GluA4 subunits. We therefore investigated synaptic AMPAr expression on these cells with immunocytochemistry following antigen-retrieval. We also examined their density of glutamatergic input (by analysing AMPAr synaptic puncta and contacts from glutamatergic boutons), and phosphorylation of extracellular signal-regulated kinases (pERKs) following noxious stimulation. Our results indicate that there are two populations of NK1r-expressing projection neurons: large GluA4(+)/GluA1(-) cells with a high density of glutamatergic input and small GluA1(+)/GluA4(-) cells with a much lower input density. Results from pERK experiments suggested that the two groups may not differ in the types of noxious stimulus that activate them. Glutamatergic synapses on distal dendrites of the large cells were significantly longer than those on proximal dendrites, which presumably compensates for the greater attenuation of distally-generated excitatory postsynaptic currents (EPSCs). Both types of cell received contacts from peptidergic primary afferents, however, on the large cells these appeared to constitute over half of the glutamatergic synapses, and were often associated with elongated AMPAr puncta. This suggests that these afferents, which probably contain substance P, provide a powerful, secure synaptic input to large NK1r-expressing projection neurons. These results demonstrate the importance of GluA4-containing AMPArs in nociceptive transmission and raise the possibility that different forms of LTP in lamina I projection neurons may be related to differential expression of GluA1/GluA4. PMID- 20303398 TI - NG peptides: a novel family of neurophysin-associated neuropeptides. AB - Neurophysins are prohormone-derived polypeptides that are required for biosynthesis of the neurohypophyseal hormones vasopressin and oxytocin. Accordingly, mutations in the neurophysin domain of the human vasopressin gene can cause diabetes insipidus. The association of neurophysins with vasopressin/oxytocin-type peptides dates back to the common ancestor of bilaterian animals and until recently it was thought to be unique. This textbook perspective on neurophysins changed with the discovery of a gene in the sea urchin Strongylocentrotus purpuratus (phylum Echinodermata) encoding a precursor protein comprising a neurophysin domain in association with NGFFFamide, a myoactive neuropeptide that is structurally unrelated to vasopressin/oxytocin type neuropeptides (Elphick, M.R., Rowe, M.L., 2009. NGFFFamide and echinotocin: structurally unrelated myoactive neuropeptides derived from neurophysin containing precursors in sea urchins. J. Exp. Biol. 212, 1067-1077). What is not known, however, is when and how the association of neurophysin with NGFFFamide like neuropeptides originated. Here I report the discovery of genes encoding proteins comprising a neurophysin domain in association with putative NGFFFamide like peptides in the hemichordate Saccoglossus kowalevskii (NGFWNamide and NGFYNamide) and in the cephalochordate Branchiostoma floridae (SFRNGVamide). Together with NGFFFamide, these peptides constitute a novel family of neuropeptides in invertebrate deuterostomes that are derived from neurophysin containing precursors and that have the sequence motif NG - "NG peptides". Genes encoding NG peptides in association with neurophysin were not found in protostomes, urochordates or vertebrates. Interestingly, however, SFRNGVamide is identical to the N-terminal region of neuropeptide S, a peptide that modulates arousal and anxiety in mammals, whilst NGFFFamide shares sequence similarity with SIFamide (AYRKPPFNGSIFamide), a neuropeptide that regulates sexual behaviour in Drosophila. Collectively, these data indicate that in an ancestor of extant deuterostomes a remarkable and unique event in the evolution of neuropeptide signalling systems occurred when a neurophysin-encoding exon(s) derived from a vasopressin/oxytocin-type neuropeptide gene became transcriptionally linked with another family of neuropeptides - NG peptides. PMID- 20303399 TI - Intra-myocardial delivery of mesenchymal stem cells ameliorates left ventricular and cardiomyocyte contractile dysfunction following myocardial infarction. AB - Although mesenchymal stem cells (MSCs) transplantation may improve the overall heart function, the heterogeneity of myocardial cells makes it difficult to determine the nature of cells benefited from transplantation. This study evaluated the effect of intra-myocardial MSC transplantation on myocardial function following MI. Enhanced green fluorescent protein (EGFP)-expressing donor MSCs from C57BL/6-Tg (UBC-GFP) 30Scha/J mice were transplanted into LV free wall in the region bordering an infarct in C57 recipient mice following ligation of left main coronary artery (MI+MSC group). Ten days after MI, LV function was assessed using echocardiography. Cardiomyocyte contractility and intracellular Ca(2+) transients were measured in cells from the area-at-risk surrounding the infarct scar. The EGFP donor cells were traced in the MSC recipient mice using fluorescence microscopy. TUNEL, H&E and Masson trichrome staining were used to assess apoptosis, angiogenesis and myocardial fibrosis, respectively. MI dilated LV as evidenced by increased end-diastolic and end-systolic diameters. MI significantly reduced fractional shortening, cardiomyocyte peak shortening, and maximal velocity of shortening and relengthening, all of which were attenuated or abrogated by MSC therapy. MI also reduced resting intracellular Ca(2+), intracellular Ca(2+) rise and decay rate, which were reconciled by MSC. MSC therapy attenuated MI-induced apoptosis and decreased angiogenesis but not myocardial fibrosis in the peri-infarct area. Taken together, our results demonstrated that MSC therapy significantly improved both LV and cardiomyocyte function possibly associated with its beneficial role in apoptosis and angiogenesis, indicating a key role for cardiomyocytes in stem cell tissue engineering. PMID- 20303400 TI - Round window delivery of dexamethasone ameliorates local and remote hearing loss produced by cochlear implantation into the second turn of the guinea pig cochlea. AB - Application of dexamethasone to the round window has been shown to ameliorate high frequency hearing loss resulting from the trauma of cochlear implantation in experimental animals, but elucidation of the factors influencing protection of the high frequencies has been confounded by the local trauma from electrode array insertion. In this experiment, a second turn cochleostomy and implantation was performed on guinea pigs, to examine protection in the basal turn without the confounding effect of local trauma, as well as to test the efficacy of hearing protection in the second cochlear turn. The implantation resulted in an increase in hearing thresholds across all frequencies examined (2-32 kHz). Local delivery of dexamethasone to the round window prior to implantation protected hearing across frequencies from 2 to 32 kHz. Auditory thresholds improved over the first week after surgery, and then remained stable for the month of the experiment. The protection of hearing in the basal turn increased with longer periods of drug application prior to implantation. The level of hearing protection in the second turn was similar irrespective of the time that the drug was applied, but was greater when a higher steroid concentration was used. It was concluded that steroids protect hearing in the basal turn of the cochlea even when there was no local trauma. The level of hearing protection in the second turn exceeded that expected from models of steroid diffusion through the cochlea, suggesting that inner ear surgery alters the distribution of dexamethasone within the cochlea. PMID- 20303401 TI - Heritability of audiometric shape parameters and familial aggregation of presbycusis in an elderly Flemish population. AB - This study describes the heritability of audiometric shape parameters and the familial aggregation of different types of presbycusis in a healthy, otologically screened population between 50 and 75 years old. About 342 siblings of 64 families (average family-size: 5.3) were recruited through population registries. Audiometric shape was mathematically quantified by objective parameters developed to measure size, slope, concavity, percentage of frequency-dependent and frequency-independent hearing loss and Bulge Depth. The heritability of each parameter was calculated using a variance components model. Logistic regression models were used to estimate the odds ratios (ORs). Estimates of sibling recurrence risk ratios (lambda(s)) are also provided. Heritability estimates were generally higher compared to previous studies. ORs and lambda(s) for the parameters Total Hearing Loss (size), Uniform Hearing Loss (percentage of frequency-dependent hearing loss) and Bulge Depth suggest a higher heredity for severe types of presbycusis compared to moderate or mild types. Our results suggest that the separation of the parameter 'Total Hearing Loss' into the two parameters 'Uniform Hearing Loss' and 'Non-uniform Hearing Loss' could lead to the discovery of different genetic subtypes of presbycusis. The parameter 'Bulge Depth', instead of 'Concavity', seemed to be an important parameter for classifying subjects into 'susceptible' or 'resistant' to societal or intensive environmental exposure. PMID- 20303402 TI - Timing is everything: temporal processing deficits in the aged auditory brainstem. AB - This summary article reviews the literature on neural correlates of age-related changes in temporal processing in the auditory brainstem. Two types of temporal processing dimensions are considered, (i) static, which can be measured using a gap detection or forward masking paradigms, and (ii) dynamic, which can be measured using amplitude and frequency modulation. Corresponding data from physiological studies comparing neural responses from young and old animals using acoustic stimuli as silent gaps-in-noise, amplitude modulation, and frequency modulation are considered in relation to speech perception. Evidence from numerous investigations indicates an age-related decline in encoding of temporal sound features which may be a contributing factor to the deficits observed in speech recognition in many elderly listeners. PMID- 20303403 TI - Effect of an overground walking training on gait performance in healthy 65- to 80 year-olds. AB - The aim of this study was to examine the effect of an individualized overground walking interval training on gait performance [i.e., speed and energy cost (C(w))] in healthy elderly individuals. Twenty-two older adults were assigned to either a training group (TG; n=12, 73.4+/-3.9yr) or a non-training control group (CG; n=10, 70.9+/-9.6yr). TG participated in a 7-week individualized walking interval training at intensities progressing from 50 to 100% of ventilatory threshold (T (VE)). Aerobic fitness [maximal oxygen uptake (V O(2max)) and T (VE)], preferred walking speed (PWS), gross and net C(w) (GC(w) and NC(w), respectively) and relative effort (%V O(2max)) at PWS measured before training (PWS(1)) were assessed prior and following the intervention. All outcomes were measured on a treadmill. Significant improvements in GC(w) (-8%; P=0.007), NC(w) (-12%; P=0.003), relative effort (%V O(2max): -12%; P<0.001) and PWS (+12%; P<0.001) were observed in TG but not in CG (P>0.71). V O(2max) and T (VE) remained unchanged in both groups (P>0.57). Changes in GC(w) at PWS(1) (difference between GC(w) at PWS(1) measured pre and post intervention) were inversely correlated with changes in PWS (difference between pre and post PWS; r= 0.67; P=0.02). The decreased C(w) at PWS(1), with no concomitant improvement in aerobic fitness, represents the main contributing factor for the reduction of the relative effort at this speed. This also allows elderly people to increase their PWS post training. Therefore, the present walking training may be an effective way to improve walking performance and delay mobility impairment in older adults. PMID- 20303404 TI - Preservation of eccentric strength in older adults: Evidence, mechanisms and implications for training and rehabilitation. AB - Overall reductions in muscle strength typically accompany the aging process. However, older adults show a relatively preserved capacity of producing eccentric strength. The preservation of eccentric strength in older adults is a well established phenomenon, occurring indiscriminately across different muscle groups, independent of age-related architectural changes in muscle structure and velocity of movement. The mechanisms for the preservation of eccentric strength appear to be mechanical and cellular in origin and include both passive and active elements regulating muscle stiffness. The age-related accumulation of non contractile material in the muscle-tendon unit increases passive stiffness, which might offer mechanical advantage during eccentric contractions. In addition, the preserved muscle tension and increased instantaneous stiffness of old muscle fibers during stretch increase active stiffness, which might enhance eccentric strength. The fact that the preservation of eccentric strength is present in people with chronic conditions when compared to age-matched healthy controls indicates that the aging process per se does not exclusively mediate the preservation of eccentric strength. Physical inactivity, which is common in elderly and people with chronic conditions, is a potential factor regulating the preservation of eccentric strength. When compared to concentric strength, the magnitude of preservation of eccentric strength in older adults ranges from 2% to 48% with a mean value of 21.6% from all studies. This functional reserve of eccentric strength might be clinically relevant, especially to initiate resistance training and rehabilitation programs in individuals with low levels of strength. PMID- 20303406 TI - Gene and protein expression of Drosophila Starvin during cold stress and recovery from chill coma. AB - In Drosophila melanogaster, the sole member of the Bcl-2-associated anthanogene (BAG)-family proteins, called Starvin (Stv), has only been recently described. BAG proteins regulate a large range of physiological processes including life/death cell balance and stress response. The role of Stv has been poorly studied in the context of abiotic stress and particularly during and after cold stress. In this study we investigated the temporal expression of Stv gene and protein in adult flies during both the cold stress (up to 9 h at 0 degrees C) and the subsequent recovery phase (up to 8 h at 25 degrees C). Because BAG proteins can regulate positively and negatively the function of Hsp70/Hsc70, we also checked whether Stv expression was related to Hsp70 and Hsc70. Stv mRNA and Stv protein both showed a similar expression pattern: no modulation during the cold period followed by a significant up-regulation during the recovery period. A coordinated response of Stv and Hsp70 mRNA was observed, but not for Hsc70. Our findings indicate that Stv expression is part of a stress-induced program in D. melanogaster. It probably acts as a co-chaperone modulating the activity of Hsp70 chaperone machinery during recovery from cold stress. Finally our results support the suggestion that Stv and human BAG3 may be functional homologs. PMID- 20303405 TI - Sex-specific social regulation of inflammatory responses and sickness behaviors. AB - In many mammals, the availability of familiar conspecifics in the home environment can affect immune function and morbidity. Numerous sex differences exist in immune responses, but whether the social environment impacts the immune system differently in males and females is not fully understood. This study examined behavioral and physiological responses to simulated bacterial infection in adult male and female Wistar rats housed either with three same-sex non siblings (Group) or alone (Isolate). Rats were injected with bacterial lipopolysaccharide (Escherichia coli LPS; 150 microg/kg, i.p.), and behavioral (orectic, locomotor, and social) and physiological (thermoregulatory, cytokine, and corticosterone) inflammatory responses were measured. Among males, LPS induced fever, suppressed locomotor activity, and inhibited feeding behavior and the magnitude of these responses were greater in Isolate relative to Group housed individuals. In contrast, among females group housing exacerbated behavioral and physiological symptoms of simulated infection. LPS treatments elicited IL-1beta production in all groups, but plasma IL-1beta concentrations were higher and peaked earlier in Isolate relative to Group males, and in Group relative to Isolate females. Furthermore, plasma concentrations of TNFalpha and IL-2 were higher in Group relative to Isolate males. Plasma corticosterone concentrations did not vary as a function of social housing conditions. Together, the data indicate that the social environment markedly influences innate immune responses. Group housing exacerbates inflammatory responses and sickness behaviors in females, but attenuates these responses in males. These sex differences are mediated in part by differential effects of the social environment on pro- and anti-inflammatory cytokine production. PMID- 20303407 TI - Co-expression of ferrochelatase allows for complete heme incorporation into recombinant proteins produced in E. coli. AB - Over-expression of heme binding proteins in Escherichia coli often results in sub optimal heme incorporation and the amount of heme-bound protein produced usually varies with the protein of interest. Complete heme incorporation is important for biochemical characterization, spectroscopy, structural studies, and for the production of homogeneous commercial proteins with high activity. We have determined that recombinant proteins expressed in E. coli often contain less than a full complement of heme because they rather are partially incorporated with free-base porphyrin. Porphyrin-incorporated proteins have similar spectral characteristics as the desired heme-loaded targets, and thus are difficult to detect, even in purified samples. We present a straightforward and inexpensive solution to this problem that involves the co-expression of native ferrochelatase with the protein of interest. The method is shown to be effective for proteins that contain either Cys- or His-ligated hemes. PMID- 20303409 TI - Neurophysiological predictor of SMR-based BCI performance. AB - Brain-computer interfaces (BCIs) allow a user to control a computer application by brain activity as measured, e.g., by electroencephalography (EEG). After about 30years of BCI research, the success of control that is achieved by means of a BCI system still greatly varies between subjects. For about 20% of potential users the obtained accuracy does not reach the level criterion, meaning that BCI control is not accurate enough to control an application. The determination of factors that may serve to predict BCI performance, and the development of methods to quantify a predictor value from psychological and/or physiological data serve two purposes: a better understanding of the 'BCI-illiteracy phenomenon', and avoidance of a costly and eventually frustrating training procedure for participants who might not obtain BCI control. Furthermore, such predictors may lead to approaches to antagonize BCI illiteracy. Here, we propose a neurophysiological predictor of BCI performance which can be determined from a two minute recording of a 'relax with eyes open' condition using two Laplacian EEG channels. A correlation of r=0.53 between the proposed predictor and BCI feedback performance was obtained on a large data base with N=80 BCI-naive participants in their first session with the Berlin brain-computer interface (BBCI) system which operates on modulations of sensory motor rhythms (SMRs). PMID- 20303408 TI - Dissociable responses to punishment in distinct striatal regions during reversal learning. AB - Adaptive behavior depends on the ability to flexibly alter our choices in response to changes in reward and punishment contingencies. One brain region frequently implicated in such behavior is the striatum. However, this region is functionally diverse and there are a number of apparent inconsistencies across previous studies. For instance, how can significant BOLD responses in the ventral striatum during punishment-based reversal learning be reconciled with the frequently demonstrated role of the ventral striatum in reward processing? Here we attempt to address this question by separately examining BOLD responses during reversal learning driven by reward and during reversal learning driven by punishment. We demonstrate simultaneous valence-specific and valence-nonspecific signals in the striatum, with the posterior dorsal striatum responding only to unexpected reward, and the anterior ventral striatum responding to both unexpected punishment as well as unexpected reward. These data help to reconcile conflicting findings from previous studies by showing that distinct regions of the striatum exhibit dissociable responses to punishment during reversal learning. PMID- 20303410 TI - Comparative mouse brain tractography of diffusion magnetic resonance imaging. AB - Diffusion magnetic resonance imaging (dMRI) tractography can be employed to simultaneously analyze three-dimensional white matter tracts in the brain. Numerous methods have been proposed to model diffusion-weighted magnetic resonance data for tractography, and we have explored the functionality of some of these for studying white and grey matter pathways in ex vivo mouse brain. Using various deterministic and probabilistic algorithms across a range of regions of interest we found that probabilistic tractography provides a more robust means of visualizing both white and grey matter pathways than deterministic tractography. Importantly, we demonstrate the sensitivity of probabilistic tractography profiles to streamline number, step size, curvature, fiber orientation distribution threshold, and wholebrain versus region of interest seeding. Using anatomically well-defined corticothalamic pathways, we show how projection maps can permit the topographical assessment of probabilistic tractography. Finally, we show how different tractography approaches can impact on dMRI assessment of tract changes in a mouse deficient for the frontal cortex morphogen, fibroblast growth factor 17. In conclusion, probabilistic tractography can elucidate the phenotypes of mice with neurodegenerative or neurodevelopmental disorders in a quantitative manner. PMID- 20303411 TI - The role of multi-area interactions for the computation of apparent motion. AB - Apparent motion (AM) is a robust visual illusion, in which fast displays of static objects in successively different positions elicit the perception of object motion. Neurons in higher order areas 21 and 19 compute object motion under such conditions and send feedback to early visual areas 18 and 17, which is instrumental in eliciting computation of motion in those very areas. To explore the computational dynamics of AM, we made a neural field model consisting of two one-dimensional rings of simple neurons expressing firing rates, one for areas 17/18 and one for areas 19/21. The model neurons, without any orientation or direction selectivity, computed apparent motion for the range of space-timings of stimuli associated with short- and long-range AM in humans. The computation of long-range AM in 17/18 required two model areas and the presence of feedback and conduction/computation delays between those areas. As in the in vivo experiments of long-range AM, the stationary stimuli were initially mapped as stationary in model area 17/18, but after the feedback also these lower areas computed AM. The dynamics of the two-area network produces short-range and long-range apparent motion for a large range of feedback strengths and a small range of lateral excitation near the bifurcation to an amplitude instability. The computation of AM in higher order areas was due to the neurons in these areas having large receptive fields as a consequence of divergent feed-forward connectivity. This implies that these areas compute long-range AM when early areas 17 and 18 do not, and therefore higher order areas must enslave lower order areas to compute the same, if the whole network is to arrive at a coherent perceptual solution. PMID- 20303412 TI - NO synthase: structures and mechanisms. AB - Production of NO from arginine and molecular oxygen is a complex chemical reaction unique to biology. Our understanding of the chemical and regulation mechanisms of the NO synthases has developed over the past two decades, uncovering some extraordinary features. This article reviews recent progress and highlights current issues and controversies. The structure of the enzyme has now been determined almost in entirety, although it is as a selection of fragments, which are difficult to assemble unambiguously. NO synthesis is driven by electron transfer through FAD and FMN cofactors, which is controlled by calmodulin binding in the constitutive mammalian enzymes. Many of the unique structural features involved have been characterised, but the mechanics of calmodulin-dependent activation are largely unresolved. Ultimately, NO is produced in the active site by the reaction of arginine with activated heme-bound oxygen in two distinct cycles. The unique role of the tetrahydrobiopterin cofactor as an electron donor in this process has now been established, but the subsequent chemical events are currently a matter of intense speculation and debate. PMID- 20303413 TI - Tumor necrosis factor-alpha converting enzyme: Implications for ocular inflammatory diseases. AB - Tumor necrosis factor-alpha (TNF-alpha) converting enzyme (TACE), a member of the family of metalloproteinase disintegrin proteins, is responsible for the conversion of inactive TNF-alpha precursor form to active mature form. TNF-alpha is a pleiotropic cytokine that contributes to cellular immunity and inflammatory response in wide range of inflammatory pathologies. Although a large number of studies indicate the use of TACE inhibitors, which prevents processing of TNF alpha as potential therapeutic drugs for the treatment of inflammatory diseases including rheumatoid arthritis, Crohn's disease and cancer, very few studies indicate its use in ocular pathologies. It is still not clearly understood how the TACE-mediated shedding of cytokines and growth factors in various ocular tissues plays a critical role in the cytotoxic signals causing tissue dysfunction and damage leading to blindness. Regulation of TACE activity is likely to have wide implications for ocular immunology and inflammatory diseases. Specifically, since anti-TNF-alpha therapies have been used to prevent ocular inflammatory complications, the use of TACE inhibitors could be a novel therapeutic approach for ocular inflammatory diseases especially uveitis. PMID- 20303414 TI - Malaria: could its unusual epigenome be the weak spot? AB - The epigenetic contribution to the regulation and maintenance of gene expression patterns by histone modifications is well established in eukaryotes. In Plasmodium falciparum, the mechanisms and factors regulating gene expression during progression through its infected red blood cell cycle (iRBC) and underlying mutually exclusive expression of antigenic variation genes involved in immune evasion are far from understood. Recently, the first comprehensive analyses of the P. falciparum chromatin landscape at different iRBC stages have been performed. These studies uncovered the existence of well-defined heterochromatic regions within a generally euchromatic epigenome. Notably, silencing of genes encoding for virulence determinants such as var genes, appears to be orchestrated by the concerted action of the Sir2 and HP1 orthologs and the presence of the histone mark, H3K9me3. Epigenetic speciation could make the parasite exquisitely vulnerable to epigenetic drug treatment, unless this deadly parasite still has a number of tricks up his sleeves. PMID- 20303416 TI - Underdiagnosis of Lynch syndrome involves more than family history criteria. AB - BACKGROUND & AIMS: Physicians' cancer-related family history assessment for Lynch syndrome is often inadequate. Furthermore, the extent to which clinicians recognize non-family history-related clues for Lynch syndrome is unclear. We reviewed an integrated electronic health record (EHR) to determine diagnostic evaluation for Lynch syndrome in patients diagnosed with colorectal cancer (CRC). METHODS: We conducted a retrospective cohort study of consecutive patients with CRC, newly diagnosed at a tertiary care Veterans Affairs facility, between 1999 and 2007. A detailed review of the EHR was conducted to evaluate the presence of family history-related and non-family history-related criteria of the Bethesda guidelines. Patient outcomes (identification in clinical practice and referral for genetic testing) were also determined. RESULTS: We identified a total of 499 patients (mean age, 65.4 years; 98.6% male; 51.1% non-Hispanic white). At least 1 of the Bethesda criteria was met for 57 patients (11.4%), none was met for 198 (39.7%), and there was uncertainty for 244 (48.9%) because of inadequate family history documentation and/or the patient was unsure about their family history. Forty-nine patients met criteria unrelated to family history. Only 4 of 57 patients (7%) who met the Bethesda guidelines had documentation of counseling. Among 244 patients with uncertainty, a suspicion for Lynch syndrome was documented in the EHR of 6 patients (2.5%); 3 received counseling. CONCLUSIONS: Lynch syndrome is under-recognized, even when patients have clear criteria unrelated to family history. Multifaceted strategies focused on reducing providers' cognitive errors and harnessing EHR capabilities to improve recognition of Lynch syndrome are needed. PMID- 20303415 TI - Membrane rafts in Alzheimer's disease beta-amyloid production. AB - Alzheimer's disease (AD), the most common age-associated dementing disorder, is pathologically manifested by progressive cognitive dysfunction concomitant with the accumulation of senile plaques consisting of amyloid-beta (Abeta) peptide aggregates in the brain of affected individuals. Abeta is derived from a type I transmembrane protein, amyloid precursor protein (APP), by the sequential proteolytic events mediated by beta-site APP cleaving enzyme 1 (BACE1) and gamma secretase. Multiple lines of evidence have implicated cholesterol and cholesterol rich membrane microdomains, termed lipid rafts in the amyloidogenic processing of APP. In this review, we summarize the cell biology of APP, beta- and gamma secretases and the data on their association with lipid rafts. Then, we will discuss potential raft targeting signals identified in the secretases and their importance on amyloidogenic processing of APP. PMID- 20303417 TI - Rabeprazole is effective in treating laryngopharyngeal reflux in a randomized placebo-controlled trial. AB - BACKGROUND & AIMS: There is controversy about the efficacy of treating patients with laryngopharyngeal reflux (LPR) using proton pump inhibitors (PPIs). We assessed the effects of high doses of the PPI rabeprazole in patients with LPR. METHODS: Patients with LPR symptoms were assigned randomly to receive rabeprazole (20 mg, twice daily, n = 42) or placebo (n = 40) for 12 weeks. All patients completed symptom questionnaires; these provided demographic information and the reflux symptom index before, during, and 6 weeks after cessation of treatment. Videolaryngostroboscopy was used to document the laryngeal findings and determine the reflux finding score. RESULTS: Twenty-four patients (57.1%) in the rabeprazole group and 27 patients (67.5%) in the placebo group had pH-documented LPR. The total reflux symptom index score decreased significantly in the group given rabeprazole, compared with patients given placebo, at weeks 6 and 12, but not at week 18. However, there were no significant differences in reflux finding scores between the rabeprazole and placebo groups at any of the time points. CONCLUSIONS: Twelve weeks of treatment with rabeprazole (20 mg, twice daily) significantly improved reflux symptoms, compared with placebo, in patients with LPR. Relapse of symptoms was observed 6 weeks after stopping PPI therapy, indicating the requirement for longer treatment duration in patients with LPR. PMID- 20303418 TI - Differential pacing for confirming mitral isthmus block: is the mitral isthmus completely blocked? PMID- 20303419 TI - Chemosensitivity recovery in Ondine's curse syndrome under treatment with desogestrel. AB - Congenital central hypoventilation syndrome (CCHS), or Ondine's curse syndrome, is a rare genetic disorder associated with mutations of the PHOX2B gene. It is characterized by sleep-related life-threatening hypoventilation that requires mechanical ventilation. The ventilatory response to hypercapnia and hypoxia is absent or dramatically reduced. Spontaneous or pharmacologically induced recovery has never been reported. We have fortuitously observed a case of CO(2) chemosensitivity recovery in a woman with CCHS who took a progestin contraceptive - desogestrel. We hypothesized that the desogestrel could be responsible for this effect. We tested this hypothesis in a second adult patient. Her lack of CO(2) chemosensitivity was documented 5 months before she was prescribed desogestrel. Three weeks after initiation of the treatment she exhibited a ventilatory and sensory response to hypercapnia. This response persisted 3 weeks later. This is the first documented case of pharmacologically restored chemosensitivity in CCHS. It suggests that a very potent progestin such as desogestrel could unveil latent chemosensitive neural circuits. PMID- 20303420 TI - Apatite content of collagen materials dose-dependently increases pre-osteoblastic cell deposition of a cement line-like matrix. AB - Bone matrix, mainly composed of type I collagen and apatite, is constantly modified during the bone remodeling process, which exposes bone cells to various proportions of mineralized collagen within bone structural units. Collagen mineralized substrates have been shown to increase osteoblast activities. We hypothesized that such effects may be explained by a rapid secretion of specific growth factors and/or deposition of specific matrix proteins. Using MC3T3-E1 seeded for 32h on collagen substrates complexed with various apatite contents, we found that pre-osteoblasts in contact with mineralized collagen gave rise to a dose-dependent deposit of Vascular Endothelial Growth Factor-A (VEGF-A) and RGD containing proteins such as osteopontin (OPN) and fibronectin (FN). This RGD matrix deposition reinforced the cell adhesion to collagen-mineralized substrates. It was also observed that, on these substrates, this matrix was elaborated concomitantly to an increased cell migration, allowing a homogeneous coverage of the sample. This particular surface activation was probably done firstly to reinforce cell survival (VEGF-A) and adhesion (OPN, FN) and secondly to recruit and prepare surfaces for subsequent bone cell activity. PMID- 20303421 TI - The effects of axial displacement on fracture callus morphology and MSC homing depend on the timing of application. AB - The local mechanical environment and the availability of mesenchymal stem cells (MSC) have both been shown to be important factors in bone fracture healing. This study was designed to investigate how the timing of an applied axial displacement across a healing fracture affects callus properties as well as the migration of systemically introduced MSC. Bilateral osteotomies were created in male, Sprague Dawley rats. Exogenous MSC were injected via the tail vein, and a controlled micro-motion was applied to one defect starting 0, 3, 10, or 24 days after surgery. The results showed that fractures stimulated 10 days after surgery had more mineral, less cartilage, and greater mechanical properties at 48 days than other groups. Populations of MSC were found in osteotomies 48 days after surgery, with the exception of the group that was stimulated 10 days after surgery. These results demonstrate that the timing of mechanical stimulation affects the physical properties of the callus and the migration of MSC to the fracture site. PMID- 20303422 TI - Potential cost-effectiveness of denosumab for the treatment of postmenopausal osteoporotic women. AB - Denosumab has recently been shown to be safe and to significantly reduce the risk of vertebral, hip and non-vertebral fractures in the "Fracture REduction Evaluation of Denosumab in Osteoporosis every 6Months" (FREEDOM) Trial. Besides the clinical profile of a new drug, it becomes increasingly important to assess whether the drug represents good value for money. This study aims to examine the potential cost-effectiveness of denosumab in the treatment of postmenopausal osteoporotic women. An updated version of a validated Markov microsimulation model was used to estimate the cost (euro2009) per quality-adjusted life-year (QALY) gained of a 3-year denosumab treatment compared with no treatment. The model was populated with cost and epidemiological data for Belgium from a health care perspective and the base-case population was defined from the FREEDOM Trial. The effect of denosumab after treatment cessation was conservatively assumed to decline linearly over 1year. Uncertainty was investigated using one-way and probabilistic sensitivity analyses. In particular, additional analyses were performed in populations (over 60 years) where osteoporosis medications are currently reimbursed in many European countries, i.e. with bone mineral density (BMD) T-score < or = -2.5 or prevalent vertebral fracture. In the base-case analysis, the cost per QALY gained of denosumab compared with no treatment was estimated at euro28,441. This value decreased to euro15,532 and to euro11,603 for women with a BMD T-score of -2.5 or prevalent vertebral fracture, respectively. Additional analyses showed that the cost-effectiveness of denosumab fall below commonly accepted threshold of euro 30,000per QALY gained for women with a BMD T score < or = -2.5 or prevalent vertebral fracture, over the entire age range examined (60-80 years). The results were robust under a wide range of plausible assumptions. In conclusion, this study suggests, on the basis of currently available data, that denosumab is cost-effective compared with no treatment for postmenopausal Belgian women with low bone mass and who are similar to patients included in the FREEDOM Trial. In addition, denosumab was found to be cost effective in population currently reimbursed in Europe with T-score < or = -2.5 or prevalent vertebral fracture, aged 60 years and above. Additional data are needed on the relative cost-effectiveness compared with other anti-osteoporotic agents and on the long-term safety of denosumab. PMID- 20303423 TI - Correspondence to Sand et Al. "Critical reappraisal of a catechol-o methyltransferase transversion variant in schizophrenia". PMID- 20303425 TI - Disambiguating inhibitory dysfunction in attention-deficit/hyperactivity disorder: toward the decomposition of developmental brain phenotypes. PMID- 20303435 TI - The global pediatrician: is there such a person, or can there be? PMID- 20303436 TI - Central nervous system connectivity after extreme prematurity: understanding autistic spectrum disorder. PMID- 20303437 TI - If your placenta doesn't have it, chances are your lungs don't have it either: the "vascular hypothesis" of bronchopulmonary dysplasia starts in utero. PMID- 20303443 TI - A young girl with weather-beaten, waxy knuckles. PMID- 20303444 TI - Booster vaccination after neonatal priming with acellular pertussis vaccine. AB - After a birth dose of acellular pertussis (aP) and diphtheria (DT)aP-hepatitis B virus (HBV)-inactivated polio vaccine (IPV)/Haemophilus influenza type b (Hib) at 2, 4, and 6 months, a booster dose of DTaP-HBV-IPV/Hib at 12 to 23 months induced strong anti-pertussis booster responses. Thus, neonatal aP priming did not lead to immune tolerance to pertussis antigens. However, it elicited bystander interference on HBV, Hib, and diphtheria responses. PMID- 20303445 TI - Bifidobacterium septicemia associated with postoperative probiotic therapy in a neonate with omphalocele. AB - We report the one case of sepsis caused by Bifidobacterium breve administered as probiotic therapy. Probiotics can be a potential cause of an invasive disease and should be used with care in vulnerable patients. PMID- 20303447 TI - Self-neglect: a challenge and a dilemma. PMID- 20303448 TI - Challenges and struggles: lived experiences of individuals with co-occurring disorders. AB - Approximately 20 million people have substance abuse disorder in a given year, and approximately 7-10 million of them will have co-occurring disorders (CODs) of both mental illness and substance abuse. Individuals with COD have higher rates of other chronic health problems (i.e., diabetes) and multiple rehospitalizations and overutilize emergent services. Despite their elevated risk for physical morbidities, there is a dearth of literature that focuses on the impact for those with COD of having multiple physical health disorders. The purpose of this interpretive study was to understand, describe, and illustrate the social and structural barriers that individuals with COD of mental illness, substance abuse, and general medical conditions encounter in regard to their health care. A purposive sampling of 20 individuals with COD (11 men and 9 women; 65% African American) were recruited from community treatment centers and supportive housing sites. Social and structural barriers to managing medical health conditions while living with COD were identified in three realms: (a) in having interpersonal relationships with health care providers, (b) in negotiating an arduous health care "system," and (c) in trying to manage health conditions while living in unstable shelter. PMID- 20303449 TI - Predictors of mental health, subjective burden, and rewards in family caregivers of patients with chronic liver disease. AB - Patients with chronic liver disease (CLD) often experience severe symptoms that cause functional impairment and necessitate assistance from a family caregiver. Few studies investigate family caregivers of patients with CLD. This descriptive correlation study described demographic characteristics, depressive and anxiety symptom levels, and prevalence of hazardous drinking, rewards, and subjective burden and explicated predictors of subjective burden and mental health status for a convenience sample of 73 family caregivers of persons with CLD. Interventions are needed to offset decreased income reported by caregivers and to treat depressive symptoms; clinically significant levels were present, and clinical referrals were warranted in this study sample. PMID- 20303450 TI - A naturalistic inquiry of registered nurses' perspectives and expectations of psychodynamic therapeutic care in acute psychiatric inpatient facilities. AB - Within contemporary inpatient mental health nursing practice, the psychodynamic model of care considered previously to be central to the nurse-patient relationship now seems a radical concept. It appears to exist only within primary care facilities and public health care practice settings. This naturalistic inquiry aimed to explicate mental health nurses' perspectives and expectations of providing psychodynamic therapeutic care in acute inpatient psychiatric facilities. Ten registered nurses working in acute inpatient mental health facilities were interviewed. Five themes emerged: a career for life, relating in a psychodynamic manner, swimming against the current, adopting a position of difference, and hopeful expectancy. PMID- 20303451 TI - Challenging normative orthodoxies in depression: Huxley's Utopia or Dante's Inferno? AB - Although there appears to be a widespread consensus that depression is a ubiquitous human experience, definitions of depression, its prevalence, and how mental health services respond to it have changed significantly over time, particularly during recent decades. Epistemological limitations notwithstanding, it is now estimated that approximately 121 million people experience depression. At the same time, it should be acknowledged that the last two decades have seen the widespread acceptance of depression as a chemical imbalance and a massive corresponding increase in the prescription of antidepressants, most notably of selective serotonin reuptake inhibitors (SSRIs). However, questions have been raised about the effectiveness and iatrogenic side effects of antidepressants; related questions have also been asked about whose interests are served by the marketing and sales of these drugs. Accordingly, this article attempts to problematize the normative orthodoxy concerning depression and creates a "space" in which an alternative can be articulated and enacted. In so doing, the article finds that the search for a world where the automatic response to depression is a pharmacological intervention not only ignores the use of alternative efficacious treatment options but may also inhibit the persons' chance to explore the meaning of their experience and thus prevent people from individual growth and personal development. Interestingly, in worlds analogous to this pharmacologically induced depression-free state, such as utopias like that in Huxley's Brave New World, no "properly conditioned citizen" is depressed or suicidal. Yet, in the same Brave New World, no one is free to suffer, to be different, or crucially, to be independent. PMID- 20303452 TI - Health-training intervention for community-dwelling elderly in the SeniorWISE Study. AB - This article describes the outcomes of a psychosocial intervention that tested whether health training could improve health and functional ability in a group of community-residing elderly persons. The health-training intervention consisted of eight 90-minute lecture and discussion classes conducted twice a week for 1 month. In 3 months following the posttest, an additional four booster sessions were delivered once per week for 1 month. Participants received a total of 20 hours of health training. The National Institutes of Health-funded SeniorWISE (Wisdom is Simply Exploration) study was advertised in the community as a program to learn strategies for successful aging. We describe the health curriculum and the health and functional outcomes for a 6-month period at preintervention, postintervention, and postbooster sessions. Complete data were available for 110 individuals. There was a statistically significant change on the Direct Assessment of Functional Status, F(2, 107) = 4.69, P < .012. Health variables remained stable over time. This intervention demonstrated that health training has the potential for noticeable improvement in Instrumental Activities of Daily Living function. PMID- 20303453 TI - Recovery paradigm: confession of the unenlightened. PMID- 20303454 TI - Looking in, looking out-increasing awareness of intentional self-harm in community populations. PMID- 20303455 TI - Updated principles and clinical caveats in the management of infection in renal transplant recipients. AB - Renal transplantation is now considered the treatment of choice for patients with end-stage renal disease. In transplant recipients, infection and rejection are entwined and are unavoidable tribulations unless clinical tolerance becomes a reality. Although rejection rates have significantly decreased with the introduction of newer immunosuppressive agents, infections remain a major cause of morbidity and mortality, and the magnitude of the problem is on the rise. Newer infections are emerging and patterns of known infections are changing. The continuous evolution of donor and recipient characteristics also alters the landscape of infections. In clinical practice, establishing a definite diagnosis of infection in a timely manner remains a challenge in transplant recipients as compared to immunocompetent individuals. Hence a comprehensive knowledge of the principles of management of infections in renal transplant recipients is very essential. In this review, we would like to provide an overview of some of the key principles that we believe are essential in the management of infectious complications in renal transplant recipients with no focus on any individual infection. PMID- 20303456 TI - Treatment with calcimimetics in kidney transplantation. AB - Graft and patient survival in renal transplantation has increased with better immune suppression treatment, leading to the appearance of new complications such as posttransplant bone disease. After renal transplantation and the recovery of renal function, mineral metabolism disorders secondary to renal failure could be expected to normalize. However, both immediately after transplantation and later, and even with good renal graft function, we see bone disorders associated to renal osteodystrophy, a high incidence of osteopenia, persistent hyperparathyroidism, hypercalcemia, hypophosphoremia, and less commonly, aseptic bone necrosis. The causes potentially responsible for these disorders have basically been identified as different degrees of renal insufficiency in the graft, persistent posttransplant secondary hyperparathyroidism, and negative impact of immunosuppression treatment, particularly corticosteroids. The most important factor in the evolution of metabolic and bone disorders after renal transplantation, however, is pretransplant bone status. Special attention should be paid to other osteoarticular complications such as loss of bone mass and fractures, leading to significant morbidity. In the therapeutic approach to these patients, as well as encouraging physical exercise and advice about diet or other habits, the use of drugs such as calcium and vitamin D supplements, bisphosphonates, and more recently, calcimimetics have made significant improvements in the prevention and treatment of bone-mineral metabolism. It has been shown that calcimimetic agents can control the parathyroid hormone, reduce episodes of hypercalcemia, and improve hypophosphatemia. Their properties have to be assessed in broader studies to establish the basis for their widespread use among renal transplant recipients. PMID- 20303457 TI - Posttransplant anemia in solid organ recipients. AB - Posttransplantation anemia (PTA) is a prevalent sequela of solid organ transplantation and a potential independent risk factor for cardiovascular morbidity and mortality in kidney transplant recipients. There are multiple causes of PTA, some of which are associated with early phase anemia (<6 months), whereas others more often induce anemia in the late posttransplant phase (>6 months). Although impaired kidney function contributes to PTA, it is only one of many factors that result in anemia in transplant recipients. Other causes include iron deficiency, medications, infections, acute rejection, inflammation, and erythropoietin deficiency. Unlike in the predialysis chronic kidney disease population, the impact of anemia after kidney transplantation outcomes is unknown. This is in large part due to the absence of controlled trials that address whether correction of anemia improves allograft function or patient morbidity and mortality. Current guidelines recommend evaluation for hemoglobin level of less than 12 g/dL and treatment when the value falls less than 11 g/dL and a target of 11 to 12 g/dL. Additional treatments may entail removing the cause of the anemia, nutritional supplementation, and/or an erythrocyte stimulating agent. PMID- 20303459 TI - Cost effectiveness analysis of hemiarthroplasty and total shoulder arthroplasty. AB - BACKGROUND: Total shoulder arthroplasty (TSA) and hemiarthroplasty (HA) are two viable surgical treatment options for glenohumeral osteoarthritis. Recent systematic reviews and randomized trials suggest that TSA, while more costly initially, may have superior outcomes with regard to pain, function and quality of life with lower revision rates. This study compared the cost-effectiveness of TSA with HA. METHODS: A Markov decision model was constructed for a cost-utility analysis of TSA compared to HA in a cohort of 64-year-old patients. Outcome probabilities and effectiveness were derived from the literature. Costs were estimated from the societal perspective using the national average Medicare reimbursement for the procedures in 2008 US dollars. Effectiveness was expressed in quality-adjusted life years (QALYs) gained. Principal outcome measures were average incremental costs, incremental effectiveness, incremental QALYs, and net health benefits. RESULTS: In the base case, HA resulted in a lower number of average QALYs gained at a higher average cost to society and was, therefore, dominated by the TSA strategy for the treatment of glenohumeral osteoarthritis. The cost effectiveness ratio for TSA and HA were $957/QALY and $1,194/QALY respectively. Sensitivity analysis revealed that if the utility of TSA is equal to, or revision rate lower than HA, TSA continues to be a dominant strategy. CONCLUSION: Total shoulder arthroplasty with a cemented glenoid is a cost effective procedure, resulting in greater utility for the patient at a lower overall cost to the payer. These findings suggest that TSA is the preferred treatment for certain populations from both a patient and payer perspective. PMID- 20303460 TI - The Disabilities of the Arm, Shoulder, and Hand questionnaire in intercollegiate athletes: validity limited by ceiling effect. AB - HYPOTHESIS: The Disabilities of the Arm, Shoulder, and Hand (DASH) questionnaire has been validated as an effective upper extremity specific outcome measure. Normative scores have not been established for young athletes. This study was conducted to establish normative DASH scores for intercollegiate athletes. We hypothesized that DASH scores in intercollegiate athletes differ from published values obtained from the general population. MATERIALS AND METHODS: The DASH questionnaire was administered to 321 athletes cleared for full participation in intercollegiate sports. Their scores were compared with normative values in the general population and 2 other age-matched cohorts. RESULTS: Intercollegiate athletes had significantly better upper extremity function compared with the general population (1.37 +/- 2.96 vs 10.10 +/- 14.68, P < .001) and an age matched cohort of employed adults (1.37 +/- 2.96 vs 5.40 +/- 7.57, P < .0001). The DASH was 0 for 65.1%. Within this cohort, men reported better upper extremity function than women (0.98 vs 1.82, P = .010). Athletes participating in overhead sports reported worse upper extremity function than nonoverhead athletes (1.81 vs 0.98, P = .042). DISCUSSION: We report normative DASH values for a group of intercollegiate athletes and show a significant difference between the scores of these athletes and the general population. Within our cohort of competitive athletes, overhead sports and female gender are associated with significantly lower DASH scores and sports module scores. The utility of using these results are limited by a substantial ceiling effect in this population of competitive athletes. Differences within our cohort and differences between our cohort and other populations are minimized by this ceiling effect. Various upper extremity outcome measures may be similarly limited by a ceiling effect and should be examined for appropriateness before use. CONCLUSION: Intercollegiate athletes report significantly greater upper extremity function than the general population; however, validity of the DASH in these athletes is limited and population differences may be minimized by a substantial ceiling effect. PMID- 20303461 TI - Failure of the hinge mechanism in total elbow arthroplasty. AB - HYPOTHESIS: Total elbow arthroplasty (TEA) has become an accepted means of dealing with intractable elbow arthritis. The Coonrad-Morrey elbow prosthesis has become the workhorse for management of elbow arthropathy. Its successful initial use in rheumatoid patients has evolved, as has its design, to allow use in osteoarthritic patients and patients with posttraumatic arthritis. More active patients with elbow arthropathy are also treated using TEA. Prior design flaws led to central bushing failure and resulted in a redesign of the implant. However, the newer design has been noted to demonstrate a new mode of failure that appears to be more prevalent in active patients with osteoarthritis and posttraumatic arthritis. The authors hypothesize that the mechanical properties of the second generation hinge mechanism are inadequate to resist the high stresses placed upon it by some active patients treated for osteo- and post traumatic arthritis. MATERIALS AND METHODS: Since 2000, 2 senior surgeons at Cleveland Clinic performed 82 TEAs, 64 in osteoarthritic or posttraumatic patients. Outcomes are reviewed. RESULTS: Five patients demonstrated failure of the central locking and bushing components, with instability and dissociation requiring revision surgery. Two of these patients had secondary failure and required repeat revision using a more substantial central axis with lock washer and set screw. DISCUSSION: The mode of failure and radiographic and clinical findings demonstrate that younger patients with a more active lifestyle are at risk for central axis and bushing failure. It is recommended that younger, more active patients be monitored indefinitely at 6-month intervals and counseled about the risk of potential failure and the need to limit forces across the reconstructed elbow. RESULTS: These failures indicate the need for alternative designs in younger, active patients. PMID- 20303462 TI - Health-related quality of life in Hispanics with chronic kidney disease. AB - Health-related quality of life (HRQOL) is an important patient-reported outcome that has gained attention in research and clinical practice. In recent years, reports of chronic kidney disease (CKD) have increased. However, not much information is available for Hispanics with CKD, a group whose rates of incidents are on the rise. This review discusses the measurement of HRQOL in CKD, with a particular focus on issues pertaining to Hispanics. Future research directions also are discussed. PMID- 20303463 TI - Telomeres and type 2 diabetes. PMID- 20303464 TI - Mean leukocyte telomere length shortening and type 2 diabetes mellitus: a case control study. AB - Recent data have implicated leukocyte telomere length shortening as a potential risk predictor for type 2 diabetes mellitus (T2DM) and its associated phenotypes. However, to date, epidemiologic data are scarce. Using a case-control study from a community-based population sample of the Boston metropolitan area (all whites: 424 controls and 432 cases), we examined the relationship of mean leukocyte telomere repeat copy number to single gene copy number (TSR) and T2DM. Associations of log(e)-transformed TSR with age, race, sex, body mass index (BMI), current smoking status, fasting insulin levels, fasting glucose levels, and hemoglobin A1c (HbA1c) were examined by multivariable linear regression analysis. A logistic regression analysis was performed to evaluate the association of log(e)-transformed TSR with T2DM with or without adjustment for potential confounders. The log(e)-transformed TSR was significantly shorter in the white cases than the white controls (P=0.003). In a multivariable linear regression analysis, an inverse association of log(e)-transformed TSR with BMI was observed (P=0.04). Furthermore, in a multivariable logistic regression analysis, decreased log(e)-transformed TSR was significantly associated with T2DM (adjusted odds ratio=1.748; 95% confidence interval [CI]=1.015-3.012; P=0.044). In summary, the current investigation has shown an association of mean leukocyte telomere length shortening with T2DM in white subjects. If corroborated in other studies, our findings suggest the potential importance of telomere biology in T2DM. PMID- 20303466 TI - Cholesterol in pleural exudates depends mainly on increased capillary permeability. AB - Pleural fluid (PF) cholesterol is a useful parameter to differentiate between pleural transudates and exudates, although the pathophysiologic mechanisms for its increase in exudates are not fully understood. We aim to elucidate the cause of this increase by analyzing the levels of cholesterol-high-density lipoproteins (HDLs), low-density lipoproteins (LDLs), apolipoprotein A (ApoA), and apolipoprotein B (ApoB)-in PF and blood as well as the number of leucocytes and red cells in the PF. We studied 259 patients with pleural effusion (57 transudates and 202 exudates). The correlations of the pleural and serum (S) levels of these parameters were analyzed, with the pleural cholesterol fractions as the dependent variables and their levels in blood and the pleural/serum protein ratio (P/S prot ratio) as the independent variables. The pleural fluid cholesterol levels (PFCHOL) correlated with their blood levels and the capillary permeability (r=0.885). No significant differences were found between the percentage of LDL, with regard to total cholesterol in the serum [SCHOL], and the same percentage in the exudates, between the PF/S LDL ratio (0.46) and the PF/S CHOL ratio (0.48), or between the PF/S ApoB ratio and the PF/S LDL ratio. The percentage of PF cholesterol bound to HDL and LDL was significantly higher (91.9%) than in the blood (90%). No significant correlations were found between any of the lipids studied and the number of erythrocytes and leucocytes. In conclusion, the PFCHOL may be predicted from the SCHOL, and the capillary permeability may be reflected by the PF/S prot ratio. PMID- 20303465 TI - Nuclear factor-kappa B (NFkappaB) component p50 in blood mononuclear cells regulates endothelial tissue factor expression in sickle transgenic mice: implications for the coagulopathy of sickle cell disease. AB - Sickle cell anemia is accompanied by the activation of coagulation and thrombosis. We have studied the abnormal expression of tissue factor (TF) by the pulmonary vein endothelium of the mild-phenotype NY1DD sickle transgenic. As detected by immunofluorescence microscopy, this occurs only after the NY1DD mouse is exposed to hypoxia/reoxygenation (H/R), which actually causes ischemia/reperfusion in the sickle cell disease-but not the normal-mouse model. We tested the hypothesis that the nuclear factor-kappa B (NFkappaB)-activating inflammation that develops in post-H/R NY1DD mice is responsible for this phenotype switch. Various NFkappaB inhibitors (including p50-specific andrographolide) demonstrated that endothelial TF positivity is NFkappaB dependent. Several systemic inflammatory stimulators (tumor necrosis factor [TNFalpha], lipopolysaccharide, thioglycollate, and carageenan) given to control mice showed that the inflammatory promotion of TF expression by only pulmonary vein endothelium is not specific to the sickle cell disease model. We bred the NFkappaB(p50)-/- state into the NY1DD mouse. Combined with marrow transplantation, this allowed the creation of NY1DD mice that were NFkappaB(p50) /- only in peripheral blood cells (and marrow) versus only in vessel walls (and tissues). This process revealed that endothelial TF expression in the NY1DD mouse is highly dependent on NFkappaB(p50) in peripheral blood mononuclear cells-but not in the vessel wall. In confirmation, the infusion of post-H/R sickle mouse blood mononuclear cells into naive NY1DD mice stimulated endothelial TF expression; the infusion of such cells from unstimulated sickle cell disease mice at ambient air did not stimulate TF expression. We conclude that peripheral blood mononuclear cells indirectly promote endothelial TF expression via a NFkappaB(p50)-dependent mechanism. This approach may be relevant to the role of coagulopathy in clinical sickle cell disease. PMID- 20303467 TI - The role of ATP-binding-cassette-transporter-A1 (ABCA1) gene polymorphism on coronary artery disease risk. AB - ATP-binding cassette transporter A1 (ABCA1) plays a pivotal role in intracellular cholesterol removal and exerts a protective effect against atherosclerosis. The role of genetic factors in susceptibility to coronary artery disease (CAD) is not clear. The aim of this study was to evaluate for the first time the possible association between R219K gene polymorphism and coronary artery disease in an Iranian adult population. A total of 207 consecutive patients with CAD (group A) and 94 patients without CAD (group B) were studied. We determined the presence of the R219K variant in the ABCA1 gene by polymerase chain reaction (PCR) and restriction analysis in 301 patients with and without CAD. The distribution of genotypes among the 2 groups was significantly different (P=0.009). In univariate analysis (with genotype AA as reference), the GG genotype was associated with a significantly increased risk of CAD (P=0.002; odds ratio [OR]=2.761; 95% confidence interval [CI]=1.418-5.374), but the GA genotype did not show a significant association (P=0.234) (data not shown). A multivariate logistic regression analysis (using sex as clinically significant variable, and using age, diabetes mellitus, low-density lipoprotein cholesterol [LDL-C], high-density lipoprotein [HDL], smoking, body mass index [BMI], and genotype as statistically significant variables) was used to determine independent associations and adjusted ORs. The GG genotype (compared with the AA genotype) was an independent predictor of CAD (OR=2.856, 95% CI=1.307-6.241; P=0.009), followed by BMI (P=0.034; OR=1.100; 95% CI=1.007-1.200). The GG genotype in the ABCA1 gene is independently associated with CAD in Iranian patients. PMID- 20303468 TI - Foreign body-induced granulation tissue is a source of adult stem cells. AB - In the current study, we have cultured and propagated the cells obtained from the granulation tissue that forms around perforated polyvinyl tubes placed in the subcutaneous space of normal rats. We found that these cells (called granulation tissue-derived stem cells [GTSCs]) expressed markers of embryonic pluripotent cells (Oct-4 and Nanog) and of adult stem cells (CXCR4 and Thy1.1) as well as produced high levels of vascular endothelial growth factor (VEGF) for up to 10 passages. By fluorescence-activated cell-sorting (FACS) analysis, GTSCs were positive for stem-cell surface markers CD90, CD59, and CD44 and were negative for CD45, which suggests that they were of mesenchymal origin and not of hematopoietic lineage. When incubated in specific differentiation medium, these cells transformed into adipogenic, osteogenic, and chondrogenic lineages, which shows that they were multipotent. Furthermore, after systemic injection, these cells were found in the vicinity of an injured site created in the liver but not in normal areas of the liver, which indicates their propensity to seek and engraft to an injured area in the body. We conclude that granulation tissue induced by a large foreign body is a convenient source of adult stem cells that can be maintained in culture and can be used to repair and regenerate injured tissue. PMID- 20303469 TI - Type 1 von Willebrand disease due to reduced von Willebrand factor synthesis and/or survival: observations from a case series. AB - It may be difficult to diagnose type 1 von Willebrand disease (VWD) because of its heterogeneous and sometimes elusive nature. To evaluate the contribution of a shorter von Willebrand factor (VWF) survival in modulating VWD phenotype, the VWF half-life was assessed in 45 type 1 VWD patients using a 24-h 1-desamino-8-d arginine vasopressin (DDAVP) test. A shorter VWF survival was observed in patients with C1130F mutations (T(1/2) elimination [T(1/2)el]=4.6+/-1.0h vs normal=15.8+/-2.3h, P<0.0001), in those with other missense mutations investigated (T(1/2)el=9.5+/-0.9h, P<0.02), and in patients not carrying VWF mutations (T(1/2)el=7.0+/-0.7h, P<0.001); the decrease mainly depended on a greater VWF clearance. VWF survival and clearance were normal in patients who carried nonsense mutations. The VWF-propeptide-to-VWF-antigen (VWF:Ag) ratio (VWFpp ratio) was higher in patients with a shorter VWF survival, and the values were inversely correlated with the VWF half-life (P<0.01). The response of VWF to DDAVP administration, which is useful to explore the synthesis and storage of VWF, was normal in patients with no mutations, whereas it decreased in patients with missense and nonsense mutations. Three scenarios, thus, are recognizable in type 1 VWD; one is associated mainly with a shorter survival of VWF, another is associated with its reduced synthesis and release, and a third is characterized by a combination of the two. The shorter VWF half-life found in patients with no VWF mutations suggests that mechanisms other than VWF might be involved in the pathogenesis of type 1 VWD. PMID- 20303471 TI - Laboratory stressors in clinically anxious and non-anxious individuals: the moderating role of mindfulness. AB - OBJECTIVE: Mindfulness forms the basis for multiple clinical interventions and has been induced in laboratory settings. However, few studies have examined the effects of dispositional or trait mindfulness. The purpose of this study was to investigate the relationship of trait mindfulness to laboratory stressor responding across fear-based anxiety disorder and non-anxious samples. We hypothesized that trait mindfulness would be associated with diminished stressor responding above and beyond the contribution of anxiety and depression-related variables, and to a greater extent in high anxiety than low anxiety individuals. METHODS: 90 participants, including 46 with anxiety disorders and 44 non-anxious controls, were assessed on hyperventilation and relaxation stressors. The relationship of trait mindfulness to stressor-related anxiety, negative affect, and duration was investigated in a hierarchical multiple regression model. RESULTS: Trait mindfulness predicted stressor responding in over 80% of measured outcomes, and predicted to a greater extent among high anxiety individuals in 50% of outcomes. CONCLUSIONS: Trait mindfulness was associated with diminished responses to laboratory stressors in clinically anxious and non-anxious samples. Implications for emotion regulation and clinical interventions are discussed. PMID- 20303470 TI - The lipid triad, or how to reduce residual cardiovascular risk? AB - Since the first interventional studies on cholesterol, many large prospective trials have demonstrated that the statins can reduce the risk of a major cardiovascular event by 25 to 35%. But, in spite of the overall decrease in LDL cholesterol in the general population over the last 20 years and treatments with statins, the persistence of a high residual vascular risk is observed in some patients. This residual risk is observed mainly in patients with atherogenic dyslipidaemia with low HDL-cholesterol, elevated triglycerides and a preponderance of small and dense LDL-cholesterol particles, a profile frequently found in patients with non-insulin dependent diabetes mellitus (NIDDM), obesity or metabolic syndrome and which has been called the "lipid triad". The frank increase in the prevalence of these metabolic abnormalities in populations worldwide casts doubt on the benefits acquired over the last few years in cardiovascular prevention. Not only does it appear essential to improve the treatment of all risk factors (hypertension, smoking, etc.), but it now seems necessary to manage all lipid parameters by decreasing LDL and also triglycerides and by increasing HDL. The development of new pathways of research and the introduction of novel compounds, which have demonstrated their clinical effectiveness, with regard to HDL in particular, are awaited. PMID- 20303472 TI - Child abuse and negative explicit and automatic self-associations: the cognitive scars of emotional maltreatment. AB - Individuals reporting Childhood Abuse (CA) (i.e., emotional neglect, emotional-, physical- and sexual-abuse) are marked by increased explicit (i.e. self-reported) negative self-associations, and an increased risk to develop depression or anxiety disorders. Automatic self-associations might play an important role in the development and maintenance of affective disorders after exposure to CA, since automatic associations are assumed to be involved in uncontrolled (spontaneous) affective behavior. This study examined whether individuals reporting a history of CA show stronger automatic (and explicit) self-depression and/or self-anxiety associations than individuals who report no CA in a large cohort study (Netherlands Study of Depression and Anxiety (NESDA), n = 2981). The Implicit Association Test (IAT) was utilized to assess automatic self-depression and self-anxiety associations. We found that CA was associated with enhanced automatic (and explicit) self-depression and self-anxiety associations. Additionally, when compared to physical- and sexual-abuse, Childhood Emotional Maltreatment (CEM; emotional abuse and emotional neglect) had the strongest link with enhanced automatic (and explicit) self-depression and self-anxiety associations. In addition, automatic and explicit negative self-associations partially mediated the association between CEM and depressive or anxious symptomatology. Implications regarding the importance of CA, and CEM in particular will be discussed. PMID- 20303473 TI - Are obsessive-compulsive tendencies related to reliance on external proxies for internal states? Evidence from biofeedback-aided relaxation studies. AB - This article presents two studies that examine the hypothesis that obsessive compulsive (OC) tendencies are associated with a general deficiency in subjective conviction, which leads to seeking and reliance on external proxies to compensate for that deficiency. We examined this hypothesis using a biofeedback-aided relaxation procedure. In Study 1 low OC participants performed better on a relaxation task than high OC participants. More importantly, viewing the biofeedback monitor (an external proxy for the internal state of relaxation) had a different effect on the two groups: Whereas high OC participants performed better, low OC participants did not. In addition, when given the opportunity, high OC participants requested the biofeedback monitor more than did the low OC participants. In Study 2 high OC participants were more affected by false biofeedback when judging their level of relaxation compared to low OC participants. Real relaxation level differences between the two false biofeedback phases among the two groups were not found. These results provide preliminary support for the hypothesis that obsessive-compulsive disorder is associated with deficient subjective conviction in internal states and increased reliance on external proxies. Implications for the understanding of OCD-related rules and rituals as well as for cognitive therapy for OCD are discussed. PMID- 20303474 TI - The N-methyl-D-aspartate receptor co-agonist D-cycloserine facilitates declarative learning and hippocampal activity in humans. AB - BACKGROUND: The N-methyl-D-aspartate receptor (NMDAR) is critical for learning related synaptic plasticity in amygdala and hippocampus. As a consequence, there is considerable interest in drugs targeting this receptor to help enhance amygdala- and hippocampus-dependent learning. A promising candidate in this respect is the NMDAR glycine-binding site partial agonist D-cycloserine (DCS). Accumulating clinical evidence indicates the efficacy of DCS in the facilitation of amygdala-dependent fear extinction learning in patients with phobic, social anxiety, panic, and obsessive-compulsive disorder. An important unresolved question though is whether the use of DCS can also facilitate hippocampus dependent declarative learning in healthy people as opposed to being restricted to the fear memory domain. METHODS: In the present study, we investigated whether or not DCS can facilitate hippocampus-dependent declarative learning. We have therefore combined functional magnetic resonance imaging with two different declarative learning tasks and cytoarchitectonic probabilistic mapping of the hippocampus and its major subdivisions in 40 healthy volunteers administered either a 250 mg single oral dose of DCS or a placebo. RESULTS: We found that DCS facilitates declarative learning as well as blood-oxygen level dependent activity levels in the probabilistically defined cornu ammonis region of the hippocampus. The absence of activity changes in visual control areas underscores the specific action of DCS in the hippocampal cornu ammonis region. CONCLUSIONS: Our findings highlight NMDAR glycine-binding site partial agonism as a promising pharmacological mechanism for facilitating declarative learning in healthy people. PMID- 20303475 TI - Epileptic feeling of multiple presences in the frontal space. AB - We describe the case of a patient who during a simple focal epileptic seizure due to vascular cerebral sequelae, reported the paroxysmal convincing feeling of the presence of several familiar persons in her peripersonal and extrapersonal space. Because the patient reported sensing multiple presences and recognizing them as family members, her case appears to contradict the hypothesis that the feeling of a non-existent human presence is an autoscopic phenomenon involving the neural "reduplication of the body". As an alternative hypothesis, I propose that the feeling of a non-existent presence may be only a hallucination of an ordinary "perception of the presence of another". Otherwise, the closest presence was felt in front of the patient, without lateralization in one hemispace, suggesting the importance to take into account other spatial dimensions than the left/right dimension, such as the front/back dimension, in the feeling of a presence. Illusory perceptive phenomena could participate in future in better understanding brain regions involved in the front/back dimension of the space perceptive representation. PMID- 20303476 TI - Testicular microlithiasis and neoplastic lesions in wild eland (Tragelaphus oryx): possible effects of exposure to environmental pollutants? AB - The purpose of the study was to compare wildlife in the proximity and away from the sources of known industrial pollution. Macroscopic, focal, gritty areas that appeared white were observed in the testes of all 24 South African eland (Tragelaphus oryx) culled in the Rietvlei Nature Reserve (RNR; n=17) between 2001 and 2003 and Suikerbosrand Nature Reserve (SNR; n=7) in 2004. Histopathological evaluation of testes showed multiple intratubular dystrophic calcifications, focal areas of sperm stasis and interstitial chronic cell infiltrates with fibrosis. Spermatogenesis was generally impaired; a few atypical germ cells were also encountered. Sertoli cell vacuolization and sloughing of the seminiferous epithelium were evident. Adenomatous changes of the rete testis, reflective of possible chronic estrogenic exposure, were found. In testes collected from three reference eland in 2007 from the Molopo Nature Reserve (MNR) in the Kalahari/Kgalagadi Desert, except for one focal area of sperm stasis and another with microcalcification, the seminiferous epithelium as well as collecting/rete tubules were normal. Analyses of fat tissue for environmental pollutants showed that 11 out of 17 RNR eland contained a detectable estrogenic chemical p nonylphenol (mean+/-SD: 184.8+/-24.6 microg/kg fat); no organochlorine chemicals or polychlorinated biphenyls were detected. Of the 7 SNR eland, 5 had detectable octylphenol residues (50.2+/-30.9 microg/kg fat), 3 had detectable p-nonylphenol (137.8+/-77.9 microg/kg fat), 3 had o-p'-DDT (114.9+/-31.1 microg/kg fat), 3 had p-p'-DDT (127.3+/-49.9 microg/kg(79.5+/-30.4 microg/kg fat) and 5 contained o-p' DDE (27.7+/-9.9 microg/kg fat). One eland from the MNR contained one 70.6 microg o-p'-DDT/kg fat and another p-p'-DDE 61.3 microg/kg fat. Therefore, in eland with testicular abnormalities, significant amounts of various estrogenic chemicals were bioaccumulated in fat samples. It therefore seems likely that the lesions found in RNR and SNR were associated with the relatively high body-burden of environmental pollutants (phenols), although the possibility of systemic infections cannot be ruled out. No testicular abnormalities were found in reference eland. These findings are the first indication of mammalian wildlife being affected by environmental pollution of endocrine disrupting chemicals in South Africa. PMID- 20303477 TI - Endocannabinoid system regulates migration of endometrial stromal cells via cannabinoid receptor 1 through the activation of PI3K and ERK1/2 pathways. AB - OBJECTIVE: To evaluate the effects of the cannabinoid system on the regulation of endometrial stromal cell (ESCs) dynamic behavior. DESIGN: ESC migration, electrical signal generated by K(+) channels, and cytoskeletal-actin dynamics were evaluated in response to treatment with the synthetic endocannabinoid methanandamide. Selective agonists and antagonists were used to identify both the receptor and the biochemical pathways involved. SETTING: Molecular research institution. PATIENT(S): Endometrial tissues were obtained from 40 reproductive age women undergoing laparoscopy for benign pathologies. INTERVENTIONS: ESCs were treated with methanadamide and with selective agonist (ACEA) and antagonist (AM251) of the cannabinoid receptor 1. MAIN OUTCOME MEASURES: Cellular migration was evaluated by means of chemotaxis experiments in a Boyden chamber. Electric signal generated by K(+) channels was evaluated by patch clamp experiments Cellular morphology and cytoskeletal-actin dynamics were evaluated by immunofluorescence. RESULT(S): Methanandamide enhanced ESC migration via cannabinoid receptor I (CNR1) through the activation of PI3K/Akt and ERK1/2 pathways. The increased ESC migration was associated with cytoskeleton reorganization identified by the dissolution of F-actin stress fibers and the presence of stress fiber arcs and with increased electrical signal generated by K(+) channels. CONCLUSION(S): In physiologic conditions, the cannabinoid system has a central role in regulating endometrial cell migration. The involvement of ERK1/2 and PI3-K/Akt pathways points to a potential role of endocannabinoids in some pathologic conditions characterized by enhanced endometrial cell invasiveness. PMID- 20303479 TI - Microdose flare versus antagonist for poor responders. PMID- 20303480 TI - Effect of vitrification and beta-mercaptoethanol on reactive oxygen species activity and in vitro development of oocytes vitrified before or after in vitro fertilization. AB - OBJECTIVE: To investigate the effect of vitrification and beta-mercaptoethanol (beta-ME) on reactive oxygen species (ROS) activity and in vitro development of oocytes vitrified before or after in vitro fertilization (IVF). DESIGN: Randomized prospective study. SETTING: University-based assisted reproductive technology laboratory. ANIMALS(S): Abattoir-derived porcine ovaries. INTERVENTIONS(S): Oocytes were vitrified either before or 4 hours after the end of IVF by solid surface vitrification (SSV) without centrifugation and/or delipation procedure. beta-ME was used to inhibit ROS activity. MAIN OUTCOME MEASURES(S): Viability was evaluated by membrane integrity and esterase enzyme activity using fluorescein diacetate staining while ROS activity was assessed by 2',7'-dichlorofluorescein assay. RESULT(S): Vitrification increased the ROS activity and decreased the viability and in vitro development of vitrified oocytes. Addition of beta-ME to vitrification and culture medium partially annihilated the ROS activity but did not improve the viability of vitrified warmed oocytes. Furthermore, beta-ME had no effect on improving the fertilization ability of oocytes vitrified at metaphase II stage but significantly increased their ability to cleave. beta-ME also increased the rate of cleavage and blastocyst formation ability of oocytes vitrified 4 hours after the end IVF. CONCLUSION(S): Vitrification increases ROS activity in oocytes that can be partially annihilated by beta-ME to obtain enhanced embryonic development. PMID- 20303481 TI - Mechanism underlying transient gestational-onset hypothyroidism-induced impairment of posttesticular sperm maturation in adult rats. AB - OBJECTIVE: To understand the mechanism underlying gestational-onset hypothyroidism-induced male infertility. DESIGN: Controlled laboratory study. SETTING: Research laboratory in a university department of endocrinology. ANIMAL(S): Wistar rat. INTERVENTION(S): Pregnant rats were exposed to methimazole from embryonic days 9 to 14, 18, and 21, covering specific fetal periods of differentiation and development of male reproductive tract organs. MAIN OUTCOME MEASURE(S): Fertility of male rats was assessed by testing sperm count, forward motility, and in vivo fertilizing ability. Secretory activity of the epididymis was evaluated by quantifying sialic acid, carnitine, and glycerylphosphorylcholine. Bioavailability of androgens was assessed by quantifying testosterone in serum and testicular interstitial fluid and epididymal 5alpha-reductase activity/mRNA expression. Androgen receptor (AR) status in the epididymis was tested by detecting the expression levels of its mRNA and protein, as well as ligand binding activity. Data were analyzed statistically by one-way analysis of variance. RESULT(S): Gestational exposure to methimazole decreased sperm forward motility, in vivo fertilizing ability, bioavailability of androgens, AR status, and secretory activity of the epididymis in adult rats. CONCLUSION(S): Transient gestational-onset hypothyroidism affects male fertility by impairing posttesticular sperm maturation process in the epididymis, owing to subnormal androgen(s) bioavailability, AR expression, and AR functional activity. PMID- 20303482 TI - Aberrant DNA methylation of imprinted H19 gene in human preimplantation embryos. AB - DNA methylation patterns of the H19 differentially methylated region were successfully determined in 32 of 50 human day 3 embryos produced and discarded after assisted reproductive technology procedures. We found methylation patterns similar to those of somatic cells in 81.3% of embryos and demethylation or hypomethylation patterns in 18.7% of embryos. PMID- 20303483 TI - Live babies born per oocyte retrieved in a subpopulation of oocyte donors with repetitive reproductive success. AB - OBJECTIVE: To investigate the oocyte-to-baby rate when controlled ovarian stimulation was performed on a highly successful donor population and to evaluate whether they produce a higher proportion of reproductively competent oocytes compared with standard donors. DESIGN: Retrospective analysis of clinical and embryological database. SETTING: University center. PATIENT(S): A total of 191 oocyte donation cycles were analyzed from 53 donors (28 best-prognosis donors and 23 standard donors). INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Total number of oocytes collected, the number of embryos transferable (fresh and frozen). and corresponding oocyte to live baby born (LBB) rates. In patients with remaining frozen embryos, the final LBB rate was estimated according to our reported rates. RESULT(S): A total of 130 oocyte retrievals from the best-prognosis donors yielded 2,470 oocytes. The total LBB per oocyte retrieved and LBB per embryo transferred was 7.3% and 24.6%, respectively. A total of 61 oocyte retrievals from the standard donors yielded 1,044 oocytes. The total LBB per oocyte and LBB per embryo transferred was 5.0% and 16.6%, respectively. This is significantly different from the best-prognosis donor group. Success rates were also analyzed after grouping donors based on the number of oocytes retrieved per cycle. In the best-prognosis group, the oocyte use rate increased significantly when fewer oocytes were retrieved, whereas the oocyte-to-baby rate was similar regardless of the number of oocytes for the standard donor group. CONCLUSION(S): This retrospective analysis revealed the existence of a subset of good-prognosis donors who produce a higher oocyte-to-baby rate that is indicative of a more biologically efficient reproductive system. Their identification, albeit a posteriori, has clinical implications for safety, by reducing ovarian hyperstimulation syndrome and multiple pregnancies, as well as for assisted reproductive technology success. PMID- 20303484 TI - Amenorrhea and "man hands". AB - A 36-year-old multiparous woman presented with amenorrhea and hyperhidrosis of 6 months' duration. Physical examination revealed large, stubby fingers and toes with soft tissue thickening. Serum growth hormone and insulin-like growth factor 1 (IGF-1) levels were elevated and a pituitary macroadenoma was found on computerized tomography (CT). PMID- 20303485 TI - Clinical and endocrine characteristics of the main polycystic ovary syndrome phenotypes. AB - OBJECTIVE: To evaluate the clinical and endocrine differences between main polycystic ovary syndrome (PCOS) phenotypes. DESIGN: To evaluate clinical and hormone parameters in a large group of consecutive women with PCOS diagnosed according Rotterdam criteria and divided according their phenotype. SETTING: University department of medicine. PATIENT(S): Three hundred eighty-two consecutive women with PCOS and 85 ovulatory controls. INTERVENTION(S): Evaluation of clinical and hormone parameters. MAIN OUTCOME MEASURE(S): Blood levels of gonadotropins, testosterone, sex-hormone-binding globulin, dehydroepiandrosterone sulfate, 17alpha-hydroxyprogesterone, progesterone, glucose, and insulin, and calculation of the free androgen index and insulin sensitivity. RESULT(S): The severe PCOS phenotype (hyperandrogenism, chronic anovulation, and polycystic ovaries: type I classic PCOS) was the most common phenotype in 53.9% of the patients. The phenotype of 8.9% of patients was characterized by hyperandrogenism and chronic anovulation but normal ovaries (type II classic PCOS). The two phenotypes of classic PCOS had similar clinical and endocrine characteristics, but the patients with polycystic ovaries had a higher luteinizing hormone/follicle-stimulating hormone (LH/FSH) ratio. Ovulatory PCOS was relatively common (28.8% of PCOS patients) and presented milder clinical and endocrine alterations than the classic PCOS phenotypes. The normoandrogenic phenotype was relatively uncommon. These patients had a normal body mass index, insulin sensitivity, and free androgen index but showed increased levels of LH and LH/FSH ratio. CONCLUSION(S): Ovulatory PCOS represents the mild form of classic PCOS, but the normoandrogenic phenotype, although part of the spectrum, may represent a different disorder or have a different pathogenetic pathway. PMID- 20303486 TI - Long-term outcomes of transvestibular vaginoplasty with pelvic peritoneum in 182 patients with Rokitansky's syndrome. AB - OBJECTIVE: To evaluate the technical feasibility and anatomical and functional outcomes of one-stage transvestibular vaginoplasty with pelvic peritoneum for the patients with Mayer-Rokitansky-Kuster-Hauser (MRKH) syndrome. DESIGN: A retrospective review of prospectively collected data. SETTING: A university hospital. PATIENT(S): A total of 182 women with MRKH syndrome. INTERVENTION(S): Undergoing transvestibular vaginoplasty with pelvic peritoneum. MAIN OUTCOME MEASURE(S): The perioperative results, complications, and anatomical and functional outcomes of transvestibular vaginoplasty with pelvic peritoneum. RESULT(S): The mean operative time was 72.2 minutes (range 55-150 minutes). Average blood loss was 78.5 mL (range 40-170 mL). The only perioperative complication was one case of rectal-vaginal fistula. Thirty-four patients had vault granulation at the neovagina, which healed after trimming and the mean length of the neovagina was 9 cm (range 7-12 cm) without any shrinkage at the follow-up of 3 months after operation. The neovaginal introitus admitted two fingers in width in all patients. Good functional outcomes were found in the patients at follow-up 15 years after surgery with 80% of the cumulative proportion of sexual satisfactory activity. CONCLUSION(S): Transvestibular vaginoplasty with pelvic peritoneum is an effective and feasible approach for women with MRKH syndrome. The procedure has satisfactory long-term anatomical and functional results. PMID- 20303487 TI - Septic shock due to Klebsiella pneumoniae after medical abortion with misoprostol only regimen. AB - OBJECTIVE: To report a case of a healthy woman who was admitted to the hospital with septic shock caused by a common uropathogen after self-administration of misoprostol for pregnancy termination. DESIGN: Case report. SETTING: Tertiary hospital. PATIENT(S): A 38-year-old woman, gravida 5, para 3, who developed septic shock after medical termination of pregnancy. INTERVENTION(S): Suction curettage, antibiotic treatment, plasma and platelet transfusions. MAIN OUTCOME MEASURE(S): Klebsiella pneumoniae was isolated from blood samples. RESULT: Ten days after her admission she was discharged home in good condition on oral antibiotics. CONCLUSION(S): Severe infections leading to septic shock from common pathogen bacteria can occur after medical termination of pregnancy, independently of the regimen used. PMID- 20303488 TI - Duodenal squamous cell carcinoma derived from the hypopharynx: immunohistochemical assessment of metastatic mechanisms. PMID- 20303489 TI - Therapeutic EUS-assisted endoscopic retrograde pancreatography after failed pancreatic duct cannulation at ERCP. AB - BACKGROUND: Cannulation of the pancreatic duct (PD) during endoscopic retrograde pancreatography (ERP) can fail even in experienced hands. A technique for therapeutic EUS-assisted rendezvous ERP has been described in a few case reports. OBJECTIVE: To investigate the efficacy and safety of therapeutic EUS-assisted ERP. DESIGN: Retrospective study. SETTING: Tertiary-care medical center. PATIENTS: This study involved 21 patients after failed ERP. INTERVENTION: EUS guided transgastric pancreatography by using a mixture of contrast media and methylene blue was attempted. If that was successful, ERP was attempted by using methylene blue flow as an indicator of the PD orifice or by a rendezvous technique using a wire passed into the PD and the small bowel through the EUS needle. MAIN OUTCOME MEASUREMENTS: Technical success rate and complications. RESULTS: The PD was of a normal diameter in 7 patients and was dilated in 14 patients. EUS-guided pancreatography was successfully done in all patients with a dilated PD but only in 4 of 7 patients (57%) with normal-diameter PDs. In 6 patients, ERP was successfully performed by using methylene blue flow as an indicator of the PD orifice. The rendezvous technique was successful in 4 of 12 cases (33%), and reasons for failure were either a tight stricture (n = 5) or a suboptimal angle of EUS needle insertion (n = 3). Overall, EUS-assisted ERP was successful in 10 of 21 patients (48%). Complications included peripancreatic abscess in 1 patient and mild pancreatitis in 1 patient. LIMITATIONS: Retrospective study, small sample size. CONCLUSION: EUS-assisted ERP is a complex procedure that can provide access to the PD in selected cases after failed standard ERP. PMID- 20303490 TI - Post-traumatic stress disorder among Chinese women survivors of intimate partner violence: a review of the literature. AB - BACKGROUND: Post-traumatic stress disorder is one of the most prevalent mental health sequelae of intimate partner violence, and as a result, it has been extensively documented in Western literature. However, whether abused women from non-Western cultures experience similar post-traumatic responses to intimate partner violence is less documented. OBJECTIVES: The objectives of this paper were (1) to review the literature for information about post-traumatic stress disorder among Chinese women survivors of intimate partner violence; (2) to provide a synthesis of the literature on post-traumatic stress disorder among abused Chinese women; and (3) to identify implications for practice and to suggest directions for research relating to post-traumatic stress disorder among abused Chinese women. DESIGN: A systematic review of the literature. DATA SOURCES: Following a systematic search for relevant literature in computerized databases and manual searches of English and Chinese language publications, five papers reporting on four studies conducted in China, Taiwan, Malaysia, and the United States were included in the review. REVIEW METHODS: Abstracts meeting the inclusion criteria were reviewed independently by two of the authors and any discrepancies were resolved by discussion. Full papers for selected abstracts were then retrieved and assessed independently by the same reviewers. RESULTS: The present literature review revealed a paucity of information relating to post traumatic stress disorder symptoms or diagnoses in abused Chinese women. Nevertheless, a link between post-traumatic stress disorder and intimate partner violence was demonstrated by the reviewed papers. CONCLUSIONS: Caution should be exercised when making comparison of the findings across the four studies because of the inherent methodological differences. Also, as the assessment tools have not been validated for culture-bound interpretation of trauma and symptom manifestation, comparisons of findings for Chinese women to women in Western literature should be undertaken with due consideration. Implications for practice and recommendations for future research are discussed. PMID- 20303491 TI - Soluble TWEAK is markedly upregulated in patients with ST-elevation myocardial infarction and related to an adverse short-term outcome. AB - OBJECTIVE: Soluble TWEAK has recently been introduced as a potential mediator of cardiovascular disease. In this retrospective pilot study we thus sought to evaluate serum levels of soluble TWEAK (sTWEAK) patients with acute ST-elevation myocardial infarction (STEMI). METHODS: Blood samples of 173 patients admitted to our hospital with acute STEMI (<24 h after symptom onset) were evaluated for their sTWEAK serum levels immediately at the time of admission and compared to those of patients with stable coronary artery disease (CAD) and healthy controls. Moreover, patients with STEMI were analyzed for their 30-day short-term outcome after acute STEMI. Adverse events were defined as the combined endpoint of cardiovascular death, resuscitation>24 h after reperfusion, cardiogenic shock or need for vasopressor therapy, repeated target vessel revascularization/myocardial infarction and stroke/TIA. RESULTS: Patients with STEMI showed significantly higher levels of sTWEAK on admission compared to control patients or patients with chronic stable coronary artery disease (p<0.0001). Moreover, sTWEAK levels were higher in female patients. Additionally, sTWEAK levels were related to C reactive protein levels and inversely correlated with the time between symptom onset and admission. Soluble TWEAK levels above the ROC-defined cutoff (>1286 pg/ml) significantly predicted an adverse short-term outcome in patients with STEMI after 30 days (p=0.0032). In this pilot study there was no significant relation between serum levels of sTWEAK and common risk factors like diabetes, hypertension, active smoking and age, white blood count or indices of myocardial function and damage like ejection fraction and infarct size in STEMI patients. Moreover, no significant relation was found between peak troponin T levels and sTWEAK on admission. CONCLUSION: Our retrospective pilot study shows for the first time that sTWEAK is significantly elevated in patients with acute myocardial infarction compared to healthy controls and patients with stable coronary artery disease. Moreover, in our study sTWEAK levels on admission were associated with an adverse short-term outcome in STEMI patients. Further work is needed to precisely define the potential role of sTWEAK as a prognostic marker in myocardial infarction. PMID- 20303492 TI - The impact of postadmission glycemia on stroke outcome: Glucose normalisation is associated with better survival. AB - BACKGROUND: Hyperglycemia on admission increases the risk of death in patients with acute stroke. It remains unclear whether glucose normalisation after admission is associated with improved survival. The goal of the study was to determine the relationship between postadmission glucose levels and mortality in stroke patients with and without admission hyperglycemia. METHODS: 302 patients with first-ever ischemic stroke and without prior diagnosis of diabetes mellitus were enrolled. Random plasma glucose level was measured on admission and fasting glucose on day 1, 2, 3, 5 and 7. Hyperglycemia on admission was defined as glucose level > or = 7.8 mmol/L. Postadmission hyperglycemia was diagnosed if mean postadmission fasting glucose level was > or = 6.1 mmol/L. RESULTS: After multivariable adjustment, postadmission hyperglycemia was associated with higher risk of death regardless of admission glucose levels (HR: 1.80, 95%CI: 1.39-2.86, P<0.01). Postadmission hyperglycemia increases risk of death in both patients with admission hyperglycemia (HR: 4.83, 95%CI: 1.93-12.06, P<0.01) and those with admission normoglycemia (HR: 1.64, 95%CI: 1.06-2.54, P=0.03). In patients with admission hyperglycemia glucose normalisation after admission was associated with reduced risk of death compared to those with persistent hyperglycemia (HR: 0.21, 95%CI: 0.08-0.52). The patients who were normoglycemic on day 1 and developed hyperglycemia on next days had increased risk of death compared to persistent normoglycemic patients (HR: 1.55, 95%CI: 1.01-2.39, P=0.04). CONCLUSIONS: Postadmission, but not admission, hyperglycemia is associated with increased risk of death. Glucose normalisation after admission is associated with better survival. PMID- 20303493 TI - Mutation of the protein kinase A phosphorylation site influences the anti proliferative activity of mitofusin 2. AB - OBJECTIVE: Mitofusin 2 (Mfn2) is an important suppressor of vascular smooth muscle cell (VSMC) proliferation. It contains a protein kinase A (PKA) phosphorylation site at serine 442 (S442) and can be phosphorylated by PKA. This study examined the role of phosphorylating specific sites on the regulation of Mfn2 protein activity in vitro and in vivo. METHODS AND RESULTS: We introduced two mutations at S442 in rat Mfn2, and investigated their effects using cultured rat VSMCs and the balloon injury model. Our results indicated that, in VSMCs, Mfn2 expression and mitochondrial morphology are affected by adenoviral-mediated overexpression of the two Mfn2 mutant proteins in the same way as the wild-type Mfn2 protein. Specifically, overexpression of the protein harboring the phospho deficient mutation Mfn2-S442A (serine replaced by alanine at residue 442) increased the inhibitory effects of Mfn2 on proliferation of VSMCs in culture, and neointimal hyperplasia and restenosis in the rat carotid artery balloon injury model at days 14 after injury. On the other hand, the phospho-mimetic mutation Mfn2-S442D (serine replaced by aspartic acid at residue 442) led to loss of growth suppressor activity. CONCLUSIONS: These results suggest that this specific PKA phosphorylation site plays a key role in Mfn2-mediated suppression of VSMC growth, which is independent of its effects on modulation of mitochondrial morphology. PMID- 20303494 TI - Apolipoprotein CIII bound to apoB-containing lipoproteins is associated with small, dense LDL independent of plasma triglyceride levels in healthy men. AB - OBJECTIVE: Plasma levels of both apolipoprotein CIII (apoCIII) and small, dense LDL particles are associated with plasma triglyceride (TG) concentrations, and are markers for cardiovascular disease (CVD) risk. We tested whether there is an association of apoCIII with small, dense LDL levels that is independent of plasma TG level. METHODS: For study I, concentrations of blood lipids, apolipoproteins, and LDL subfractions (analytical ultracentrifugation, AnUC) were measured in 141 healthy middle-aged males. In study II (n=14), density gradient ultracentrifugation of plasma was performed, and 3 fractions in the LDL density range (1.019-1.063 g/ml) were collected. RESULTS: In study I, plasma levels of apoCIII in apoB-containing lipoproteins (LpB:CIII) were associated positively with concentrations of LDL3 (p<0.001) and LDL4 (p<0.001) and negatively with LDL peak particle size (p<0.05) with adjustment for plasma TG. Stepwise multiple regression analysis showed that LpB:CIII was significantly associated with small, dense LDL (LDL3+LDL4) levels after adjusting for age, BMI, plasma levels of TG, apoB, and HDL-cholesterol. In study II, the molar ratio of apoCIII to apoB in the LDL fraction of highest density (1.049-1.064 g/ml) was found to be significantly greater (p<0.001) than that in each of two LDL fractions of lower density (1.033 1.038 g/ml; p<0.001 and 1.038-1.049 g/ml; p<0.001). CONCLUSIONS: Increased apoCIII content may contribute to metabolic and pathologic properties of small, dense LDL particles. PMID- 20303495 TI - Fast determination of synthetic polycyclic musks in sewage sludge and sediments by microwave-assisted headspace solid-phase microextraction and gas chromatography-mass spectrometry. AB - One-step in situ microwave-assisted headspace solid-phase microextraction (MA-HS SPME) followed by gas chromatography-mass spectrometry (GC-MS) analysis is presented as a fast and solvent-free technique to determine synthetic polycyclic musks in sewage sludge and sediment samples. Six synthetic polycyclic musks (galaxolide (HHCB), tonalide (AHTN), celestolide (ADBI), traseolide (ATII), cashmeran (DPMI) and phantolide (AHMI)) were selected in the method development and validation. The effects of extraction parameters for the quantitative extraction of these analytes by one-step MA-HS-SPME were systematically investigated. The dewatered solid sample mixed with 20-mL deionized water (containing 3 g of NaCl in a 40-mL sample-vial) was efficiently extracted by a polydimethylsiloxane-divinylbenzene (PDMS-DVB) fiber placed in the headspace when the extraction slurry was microwave irradiated at 80 W for 5 min. The limits of detection (LODs) ranged from 0.04 to 0.1 ng/g, and the limits of quantification (LOQs) ranged from 0.1 to 0.3 ng/g (fresh weight). A preliminary analysis of sludge and sediment samples revealed that HHCB and AHTN were the two most commonly detected synthetic polycyclic musks; using a standard addition method, their total concentrations were determined to range from 0.3 to 10.9 ng/g (fresh weight) with relative standard deviation (RSD) ranging from 4% to 10%. PMID- 20303496 TI - Sensitive determination of rhodamine 110-labeled monosaccharides in glycoprotein by capillary electrophoresis with laser-induced fluorescence detection. AB - Rhodamine 110 (Rho110) has been used in the highly sensitive analysis of monosaccharides, as it reacts with the reducing carbonyl group of the saccharides. The monosaccharide derivatives were investigated by capillary electrophoresis with laser-induced fluorescence detection. The derivatization was performed at 90 degrees C for 30 min for all monosaccharides. The derivatized monosaccharides were separated using 200 mM borate (pH 10.5) as running buffer within 20 min. The fluorescence intensities of Rho110-derivatives were significantly decreased by the presence of excess reducing agent, but were greatly increased by the addition of potassium hexacyanoferrate(III). The concentration and mass detection limits for monosaccharides were in the range of 1.4-2.8 nM and 36-70 amol, respectively. We have applied this derivatization method to the analysis of the composition of monosaccharides in glycoproteins (ribonuclease B, fetuin, and erythropoietin) following their subjection to strong acid hydrolysis. The results from these analyses were in good agreements with the reported values established previously. PMID- 20303497 TI - Separation of alpha-cyclohexylmandelic acid enantiomers using biphasic chiral recognition high-speed counter-current chromatography. AB - This work concentrates on a chiral separation technology named biphasic recognition applied to resolution of alpha-cyclohexylmandelic acid enantiomers by high-speed counter-current chromatography (HSCCC). The biphasic chiral recognition HSCCC was performed by adding lipophilic (-)-2-ethylhexyl tartrate in the organic stationary phase and hydrophilic hydroxypropyl-beta-cyclodextrin in the aqueous mobile phase, which preferentially recognized the (-)-enantiomer and (+)-enantiomer, respectively. The two-phase solvent system composed of n-hexane methyl tert-butyl ether-water (9:1:10, v/v/v) with the above chiral selectors was selected according to the partition coefficient and separation factor of the target enantiomers. Important parameters involved in the chiral separation were investigated, namely the types of the chiral selectors (CS); the concentration of each chiral selector; pH of the mobile phase and the separation temperature. The mechanism involved in this biphasic recognition chiral separation by HSCCC was discussed. Langmuirian isotherm was employed to estimate the loading limits for a given value of chiral selectors. Under optimum separation conditions, 3.5-22.0 mg of alpha-cyclohexylmandelic acid racemate were separated using the analytical apparatus and 440 mg of racemate was separated using the preparative one. The purities of both of the fractions including (+)-enantiomer and (-)-enantiomer from the preparative CCC separation were over 99.5% determined by HPLC and enantiomeric excess reached 100% for the (+/-)-enantiomers. Recovery for the target compounds from the CCC fractions reached 85-88% yielding 186 mg of (+) enantiomer and 190 mg of (-)-enantiomer. The overall experimental results show that the HSCCC separation of enantiomer based on biphasic recognition, in which only if the CSs involved will show affinity for opposite enantiomers of the analyte, is much more efficient than the traditional monophasic recognition chiral separation, since it utilizes the cooperation of both of lipophilic and hydrophilic chiral selectors. PMID- 20303498 TI - The rheology of concentrated suspensions of arbitrarily-shaped particles. AB - We propose an improved effective-medium theory to obtain the concentration dependence of the viscosity of particle suspensions at arbitrary volume fractions. Our methodology can be applied, in principle, to any particle shape as long as the intrinsic viscosity is known in the dilute limit and the particles are not too elongated. The procedure allows to construct a continuum-medium model in which correlations between the particles are introduced through an effective volume fraction. We have tested the procedure using spheres, ellipsoids, cylinders, dumbells, and other complex shapes. In the case of hard spherical particles, our expression improves considerably previous models like the widely used Krieger-Dougherty relation. The final expressions obtained for the viscosity scale with the effective volume fraction and show remarkable agreement with experiments and numerical simulations at a large variety of situations. PMID- 20303499 TI - Effect of annealing on the phase structure and the properties of the film formed from P(St-co-BA)/P(MMA-co-BA) composite latex. AB - Composite latex of P(St-co-BA)/P(MMA-co-BA) was prepared by two-step semi continuous emulsion polymerization under starved conditions. Optical properties, water resistance and heat aging process of the film formed by the composite latex were examined. It was revealed that annealing temperature played an important role on the structure of the composite latex film. The surface of the film prepared at room temperature was very rough. Many micro-cracks were observed both on the surface and inside of the film. Increase of annealing temperature assisted film formation. There was a critical temperature at which the film properties, such as water resistance and transparency, were significantly improved. However, it was worth to note that phase rearrangement had occurred when the annealing temperature was higher than critical temperature. Micro-pinholes and micro-cracks were detected on the surface of the film. Meanwhile, the properties of the film, such as transparency and water adsorption, became remarkable deteriorated. PMID- 20303501 TI - Structure of the SDS/1-dodecanol surfactant mixture on a graphite surface: a computer simulation study. AB - Molecular dynamics simulations of mixtures of sodium dodecyl sulfate (SDS) and 1 dodecanol molecules on a graphite surface were carried out at low and high concentration to investigate the formation of aggregates on the solid plate. The simulations showed that at low concentration the surfactants were well adsorbed on the surface by forming layers structures or a hemicylinder aggregate for a slightly higher surfactant concentration whereas at the highest concentration the surfactants formed monolayer-like structures localized away from the graphite surface with a water bin between the monolayer and the graphite plate. Therefore, we obtained different arrays of those observed in recent simulations of pure SDS adsorbed on graphite at the same concentration reported in the literature. The unexpected water layer between the 1-dodecanol and the graphite surface, at the highest concentration, was explained in terms of the Hamaker constants. The present results suggest that the formation of aggregates on solid surfaces is a combined effect not only of the surfactant-surfactant and the surfactant-wall interactions but also of the surfactant concentration. PMID- 20303500 TI - Direct electrochemistry and electrocatalysis of myoglobin immobilized on Fe2O3 nanoparticle-sodium alginate-ionic liquid composite-modified electrode. AB - A biocomposite material composed of sodium alginate (SA), Fe(2)O(3) nanoparticles, and ionic liquid 1-decyl-3-methylimidazolium bromide ([DMIM]Br) was fabricated and used for the immobilization of myoglobin (Mb) on the surface of a carbon ionic liquid electrode (CILE). The CILE was fabricated by mixing graphite powder with ionic liquid N-butylpyridinium hexafluorophosphate (BPPF(6)) together. UV-Vis absorption and FTIR spectroscopic results indicated that Mb retained its native structure in the composite material. A pair of well-defined redox peaks appeared on the cyclic voltammogram in pH 7.0 phosphate buffer solution (PBS) with the formal peak potential (E(0')) at -0.256 V (versus SCE), which was the typical electrochemical behavior of Mb heme Fe(III)/Fe(II) redox couples. The Mb-modified electrode showed good electrocatalytic activity to the reduction of trichloroacetic acid (TCA) and NaNO(2) with wide linear range, good sensitivity, and reproducibility. The calibration range for TCA detection was between 0.6 and 12.0 mmol L(-1) with the linear regression equation as Iss (MUA)=42.44C (mmol L(-1))+50.57 and a detection limit of 0.4 mmol L(-1) (3sigma). The Mb-modified electrode also applied to NaNO(2) determination in the concentration range from 4.0 to 100.0 mmol L(-1) with a detection limit of 1.3 mmol L(-1) (3sigma). So the proposed electrode has potential applications as third-generation biosensors. PMID- 20303502 TI - SAXS exploration of the synthesis of ultra monodisperse silica nanoparticles and quantitative nucleation growth modeling. AB - The production of highly monodisperse nanoparticles of precisely controlled size is a very important research field. It has important applications notably for the optical properties of nanoparticles (e.g. quantum dot) or nanoparticle assemblies (e.g. photonic band gap crystals) and for electromagnetic properties (e.g. information storage). Understanding monodisperse nanoparticle synthesis mechanism is based mostly on the Classical Nucleation Theory (CNT). It has been shown in the literature and in this work that CNT is able to predict the nanoparticle concentration and average size correctly. However, until recently only a few models based on CNT were able to predict the size distribution of the synthesized objects. In this work, we show that a CNT based model is not able to predict the size distribution of silica nanoparticles formed in a pure La Mer like nucleation growth process. Reasons for this discrepancy are discussed and should be taken into account to develop more complete models able to predict the size distribution especially if it is desired to use them as tools to optimize monodispersity. PMID- 20303503 TI - Charging of silver bromide aqueous interface: evaluation of interfacial equilibrium constants from surface potential data. AB - A single crystal silver bromide electrode (SCr-AgBr) was used to measure the inner surface potential (Psi(0)) at the silver bromide aqueous electrolyte interface as a function of the activities of Br(-) and Ag(+). Absolute values of the surface potential were calculated from electrode potentials of SCr-AgBr using the value of point of zero charge (pBr(pzc)=6.9 [H.A. Hoyen, R.M. Cole, J. Colloid Interface Sci. 41 (1972) 93.]) as the value of point of zero potential. Measurements were performed in potassium nitrate aqueous solutions. The Psi(0)(pBr) function was linear and slightly dependent on the ionic strength. The reduction values of the slope with respect to the Nernst equation, expressed by the alpha coefficient, were 0.880,0.935, and 0.950 at ionic strengths of 10(-4), 10(-3), and 10(-2) mol dm(-3), respectively. The results were successfully interpreted by employing the surface complexation model, developed originally for metal oxides and adapted for silver halides. The thermodynamic ("intrinsic") equilibrium constants for binding of bromide (K(n)(?)) and silver (K(p)(?)) ions on the corresponding sites at the silver bromide surface were evaluated as lgK(n)(?)=3.98; lgK(p)(?)=2.48. Symmetrical counterion surface association was assumed and equilibrium constants were obtained as lgK(NO(3)( ))(?)=lgK(K(+))(?)=4.30. PMID- 20303504 TI - Prevalence of Proteus mirabilis in skin abscesses of the axilla. AB - Gram-positive organisms are the most common infectious etiologic agents in skin abscesses. Empiric antimicrobial treatment choices are influenced by this knowledge. In this report, we describe a high prevalence of Proteus mirabilis, a Gram-negative bacillus, in skin abscesses of the axilla, which has potential implications for selection of antimicrobial therapy. PMID- 20303505 TI - Qualitative analysis of beliefs and perceptions about sudden infant death syndrome in African-American mothers: implications for safe sleep recommendations. AB - OBJECTIVE: To investigate, by using qualitative methods, perceptions about sudden infant death syndrome (SIDS) in African-American parents and how these influence decisions. STUDY DESIGN: Eighty-three mothers participated in focus groups or individual interviews. Interviews probed reasons for decisions about infant sleep environment and influences affecting these decisions. Data were coded, and themes were developed and revised in an iterative manner as patterns became more apparent. RESULTS: Themes included lack of plausibility, randomness, and vigilance. Many mothers believed that the link between SIDS and sleep position was implausible. Because the cause of SIDS was unknown, they did not understand how certain behaviors could be defined as risk factors. This confusion was reinforced by perceived inconsistency in the recommendations. Most mothers believed that SIDS occurred randomly ("God's will") and that the only way to prevent it was vigilance. CONCLUSIONS: Many African-American mothers may not understand the connection between SIDS and sleep behaviors or believe that behavior (other than vigilance) cannot affect risk. These beliefs, if acted on, may affect rates of safe sleep practices. Efforts to explain a plausible link between SIDS and safe sleep recommendations and to improve consistency of the message may result in increased adherence to these recommendations. PMID- 20303507 TI - Anticoagulation management during cardiopulmonary bypass: a survey of 54 North American institutions. PMID- 20303506 TI - Prevalence of extreme obesity in a multiethnic cohort of children and adolescents. AB - OBJECTIVE: To estimate the prevalence of extreme obesity in a large, multiethnic contemporary cohort of children and adolescents. STUDY DESIGN: In a cross sectional study, measured weight and height were extracted from electronic medical records of 710,949 patients aged 2 to 19 years (87.8% of eligible patients) who were enrolled in an integrated prepaid health plan in 2007 and 2008. Prevalence of extreme obesity was defined as body mass index (BMI)-for age>or=1.2 times 95th percentile or BMI>or=35 kg/m2. RESULTS: Extreme obesity was observed in 7.3% of boys and 5.5% of girls. The prevalence peaked at 10 years of age in boys and at 12 years of age with a bimodal distribution in girls (second peak at 18 years; P value for sex x age interaction=.036). The prevalence of extreme obesity varied in ethnic/racial and age groups, with the highest prevalence in Hispanic boys (as high as 11.2%) and African-American girls (as high as 11.9%). CONCLUSION: Extreme obesity in Southern California youth is frequently observed at relatively young ages. The shift toward extreme body weights is likely to cause an enormous burden of adverse health outcomes once these children and adolescents grow older. PMID- 20303508 TI - Is early antithrombotic therapy necessary in patients with bioprosthetic aortic valves in normal sinus rhythm? AB - OBJECTIVE: Current American Heart Association/American College of Cardiology guidelines recommend anticoagulation and antiplatelet therapy during the first 90 postoperative days; however, there is wide variability in the administration of antithrombotic therapy after bioprosthetic aortic valve replacement. We sought to determine whether early antithrombotic therapy was necessary in patients undergoing isolated bioprosthetic aortic valve implantation and who were discharged in normal sinus rhythm. METHODS: From December 2001 to October 2008, 1131 patients underwent isolated bioprosthetic aortic valve implantation at Brigham and Women's Hospital. After exclusion of patients who underwent concomitant operations (n = 138, 12%), patients who were anticoagulated preoperatively (n = 4, 0.4%), and patients who experienced postoperative refractory atrial fibrillation requiring anticoagulation at discharge (n = 128, 11%), our study base consisted of 861 patients. Patients were followed for 90 days postoperatively for the occurrence of thromboembolism, including stroke, transient ischemic attack, or peripheral thromboembolic events and bleeding complications. RESULTS: Of the 861 patients included in this study, 133 (15%) were anticoagulated with warfarin sodium (AC+) postoperatively and 728 (85%) were not (AC-). Patients who received postoperative anticoagulation were older; had a higher incidence of hypertension, cerebrovascular accident, and pulmonary vascular disease; and were more symptomatic at presentation. The 90-day risk of thromboembolism (cerebrovascular accident, transient ischemic attack, or peripheral thromboembolism) after surgery was 5% (n = 6) in those who were anticoagulated and 5% (n = 39) in those who were not (P = .67). Independent predictors of thromboembolism were found to be increasing age (odds ratio, 1.03; P = .03), female gender (odds ratio, 2.23; P = .005), short stature (odds ratio, 0.97; P = .002), smoking status (P = .05), New York Heart Association III/IV (odds ratio 1.77, P = .04), and a 19-mm bioprosthetic aortic valve prosthesis (odds ratio, 2.22; P = .03). Evaluation of each predictor with postoperative acetylsalicylic acid+ and AC+ interaction terms revealed that female patients (odds ratio, 0.75; P = .03 AC+; odds ratio, 0.66; P = .02 acetylsalicylic acid+) and patients with a 19-mm bioprosthetic aortic valve (odds ratio, 0.65; P = .02 AC+; odds ratio, 0.36; P = .01 acetylsalicylic acid+) had a reduction in the incidence of thromboembolism when administered acetylsalicylic acid or warfarin sodium. Patients who were in New York Heart Association III/IV also had a reduction of thromboembolism when given vitamin K antagonist (odds ratio, 0.73; P = .04); a similar trend was observed in patients given acetylsalicylic acid (odds ratio, 0.34; P = .06). CONCLUSION: Early anticoagulation after isolated bioprosthetic aortic valve replacement in patients in normal sinus rhythm does not seem to reduce the risk of thromboembolism except in high-risk groups. Current recommendations should be revisited, because the only patients who may benefit from anticoagulation are female, those who are highly symptomatic, and those with a small aortic prosthesis. PMID- 20303510 TI - Squamous cell carcinoma of the renal pelvis. PMID- 20303512 TI - Optical coherence tomography of human kidney. AB - PURPOSE: To determine histopathological status of living human kidneys in real time and a noninvasive fashion would be a significant advancement in renal disease diagnosis. Recently we reported that optical coherence tomography has the requisite high spatial resolution to noninvasively determine histopathological changes in rodent kidneys with microm scale resolution. We established whether optical coherence tomography could 1) effectively penetrate the connective tissue capsule surrounding human kidneys, 2) provide a global survey of the human renal surface and 3) determine histopathological changes in human renal microstructure. MATERIALS AND METHODS: Using a high speed optical coherence tomography system equipped with a frequency swept laser light source (1.3 microm wavelength) we obtained cross-sectional images of 4 ex vivo human kidneys. All scanned sections underwent subsequent conventional light microscopic histological analysis, allowing direct comparisons. RESULTS: Optical coherence tomography enabled characterization of the tubules, glomeruli and cortical vessels with a penetration depth of up to 2 mm and 10 microm spatial resolution. We surveyed and imaged an entire human kidney within minutes in a noninvasive fashion. Acquired optical coherence tomography images documented histopathological changes in the tubules, glomeruli and interstitium that closely matched the conventional histological observations. CONCLUSIONS: Optical coherence tomography resolution and low cost, and the versatility of the probes required for imaging acquisition make this optical technology a promising modality to diagnose renal pathology. PMID- 20303514 TI - Re: Radical prostatectomy findings in patients in whom active surveillance of prostate cancer fails. A. S. Duffield, T. K. Lee, H. Miyamoto, H. B. Carter and J. I. Epstein. J Urol 2009; 182: 2274-2278. PMID- 20303515 TI - Cost-benefit analysis of scrotal ultrasound in treatment of adolescents with varicocele. AB - PURPOSE: Varicoceles are a major cause of male factor infertility, although management of adolescent varicoceles is controversial. Most clinicians advocate repair if there is a persistent testicular size discrepancy of greater than 20%. Using previously published data, we performed a cost-benefit analysis of testicular ultrasound vs orchidometry to evaluate for this size difference. MATERIALS AND METHODS: We performed a PubMed search using the terms "adolescent varicocele," "ultrasound and varicocele," and "testis size and varicocele." Using the data from the relevant studies and Medicare reimbursement data from our region, we determined the cost of missing a persistent testicular size difference of greater than 20%. RESULTS: Approximately 25% of adolescents with varicocele have a persistent size discrepancy of greater than 20%. Approximately 40% of this group would be identified as having a size discrepancy with conventional orchidometry. The annual cost of ultrasound for every adolescent male with a varicocele would be $364 million if the imaging were done in an office based setting. If the testing were done at a hospital, the annual cost would be $795 million. The cost per case of missed persistent size discrepancy spanning 3 years is approximately $5,597 for office ultrasound and $12,226 for hospital ultrasound. CONCLUSIONS: There is limited evidence that adolescent varicocele repair improves paternity in adulthood. In an era of increasing health care costs the expense of ultrasound to evaluate for size discrepancy is significant and should be thoughtfully evaluated. PMID- 20303516 TI - Editorial comment. PMID- 20303517 TI - Urinary neutrophil-gelatinase associated lipocalin is a potential noninvasive marker for renal scarring in patients with vesicoureteral reflux. AB - PURPOSE: Renal scarring is a serious complication that often occurs with chronic pyelonephritis in the presence of vesicoureteral reflux. In a previous study we established a rat model of renal scarring in which we found the up-regulation of neutrophil-gelatinase associated lipocalin at the mRNA and protein levels. In this study we evaluated urinary neutrophil-gelatinase associated lipocalin as a potential biomarker for progression of renal scarring in patients with vesicoureteral reflux. MATERIALS AND METHODS: A total of 34 patients diagnosed with vesicoureteral reflux without evidence of current urinary tract infection and 28 normal healthy children were enrolled in this study. Renal scars were evaluated by (99m)technetium dimercapto-succinic acid renal scan in 24 of the reflux cases. Urinary neutrophil-gelatinase associated lipocalin levels were monitored by ELISA. RESULTS: In normal subjects urinary neutrophil-gelatinase associated lipocalin was high during infancy, decreased rapidly within the following year and reached a low stable level from age 3 years onward. Urinary neutrophil-gelatinase associated lipocalin levels, normalized to age matched standards, were significantly increased in patients with vesicoureteral reflux compared to controls. These levels did not correlate with reflux grade, but were significantly higher in patients with radiological evidence of renal scarring irrespective of reflux grade. CONCLUSIONS: Estimation of urinary neutrophil gelatinase associated lipocalin may be useful as a noninvasive diagnostic or prognostic biomarker for renal scarring. PMID- 20303518 TI - Outcome of transcatheter arterial embolization for bladder and prostate hemorrhage. AB - PURPOSE: We evaluated the efficacy and outcomes of transcatheter arterial embolization for intractable bladder or prostate bleeding after failed conservative treatment. MATERIALS AND METHODS: We retrospectively studied the records of 2 women and 18 men with a mean +/- SD age of 73 +/- 17.2 years referred between 1999 and 2008 for selective pelvic angiography after failed conventional therapy. Embolization was feasible in 18 patients, including bilateral and unilateral embolization in 13 and 5, respectively. It consisted of superselective distal particulate or glue embolization of the vesical or prostatic arteries in 11 patients, selective proximal coil or gelatin sponge particle occlusion of the anterior division of the internal iliac artery in 2, the 2 techniques in 3 and coil blockade in 2. Clinical bleeding control and post embolization angiography findings were used to assess outcomes. RESULTS: The technical success rate was 90% (18 of 20 cases). Bleeding was controlled after the first procedure in 15 of 18 patients (83.3%) and after a repeat procedure in the remaining 3. The periprocedural mortality rate was 20% (4 of 20 patients) and all deaths were related to underlying conditions. No major complications related to catheterization occurred. Late bleeding recurrence was reported in 4 of the 14 survivors (28.6%). Mean post-embolization followup was 16 months (range 15 days to 56 months). During followup 6 more patients died, including 2 of repeat bleeding. CONCLUSIONS: Selective angiographic embolization is safe and effective to control refractory, life threatening bladder or prostate bleeding. This procedure should be considered the treatment of choice since it usually obviates the need for emergency surgery in these severely ill patients. PMID- 20303519 TI - Readability of health related quality of life instruments in urology. AB - PURPOSE: The average American adult reads at a fifth to eighth-grade level, with wide variability, presenting challenges for the assessment of self-reported health related quality of life. We identified the health related quality of life instruments used in patients with urological diseases and evaluated their readability. MATERIALS AND METHODS: We focused on the most burdensome urological diseases, based on total expenditures in the United States. We then identified disease specific instruments by systematically searching PubMed, the Cochrane Database of Systematic Reviews, Google, Google Scholar, the Patient Reported Outcome and Quality of Life Instruments Database (Mapi Research Institute, Lyon, France) and Yahoo! for health related quality of life studies in patients with these urological conditions. Where disease specific instruments were lacking, we noted the general health related quality of life measures most commonly used. For each instrument, we calculated the median Flesch-Kincaid grade level, the proportion of questionnaire items below an eighth-grade reading level, the mean Flesch Reading Ease, and the mean number of words per sentence and characters per word, all of which are validated measures of readability. RESULTS: The average +/ SD of the median Flesh-Kincaid reading levels was 6.5 +/- 2.1 (range 1.0 to 12.0). Of the 76 instruments 61 (80%) were at or below an eighth-grade reading level. The mean reading ease was greater than 30 for each of the 76 questionnaires and greater than 60 for 66 (87%). Urinary tract infection, the costliest urological disease, has only 1 disease specific health related quality of life measure. Urolithiasis, the second costliest, has none. CONCLUSIONS: The reading level of health related quality of life questionnaires in urology is appropriate for the reading ability of most adults in the United States. However, the most burdensome urological diseases lack disease specific health related quality of life instruments. PMID- 20303520 TI - The EGFR polymorphism rs884419 is associated with freedom from recurrence in patients with resected prostate cancer. AB - PURPOSE: Prognostic biomarkers are needed to optimize treatment decisions for prostate cancer. Single nucleotide polymorphisms participate in the individual genetic background modulating risk and clinical outcomes of cancer. We tested whether EGFR polymorphisms are associated with prostate cancer clinical outcomes. MATERIALS AND METHODS: The study population consisted of 212 patients with clinically localized prostate cancer treated with radical prostatectomy from 1997 to 1999. Resected prostatic tissues were genotyped with allele specific probes for 9 haplotype tagging single nucleotide polymorphisms, which were located in intronic, exonic and flanking regions of linkage disequilibrium in the EGFR gene. Correlations between alleles, and recurrence and survival data were investigated using univariate and multivariate genetic analysis models. RESULTS: There was a statistically significant association between the single nucleotide polymorphism rs884419 and prostate cancer recurrence, as defined in the study by at least prostate specific antigen biochemical recurrence (log rank test p <0.001). The incidence of the recurrence risk enhancing genotype A/A was 3.1% vs 17.4% and 80% for the risk decreasing genotypes A/G G/G, respectively. Based on Cox proportional hazard regression modeling patients carrying G/G and A/G genotypes were associated with a decreased risk of prostate cancer recurrence compared to those with the A/A genotype (HR 0.10, 95% CI 0.02-0.41 and 0.13, 95% CI 0.04 0.46, respectively, p <0.002). CONCLUSIONS: These data suggest that a polymorphism flanking the EGFR gene is an independent prognostic genetic biomarker that predicts prostate cancer biochemical recurrence after radical prostatectomy. PMID- 20303521 TI - High incidence of vesicoureteral reflux in mice with Fgfr2 deletion in kidney mesenchyma. AB - PURPOSE: Mice with Fgfr2 conditional deletion in metanephric mesenchyma (Fgfr2(Mes-/-)) have ureteral bud induction abnormalities. We determined whether Fgfr2(Mes-/-) mutants developed abnormally positioned ureters predisposing to vesicoureteral reflux. MATERIALS AND METHODS: We measured common nephric duct length and assayed for apoptosis in embryonic day 11.5 mice. We performed 3 dimensional reconstruction of, and real-time polymerase chain reaction and whole mount in situ hybridization for Fgfr2 in urinary tracts in embryonic day 15.5 embryos. We also performed cystograms followed by 3-dimensional reconstruction in postnatal animals. RESULTS: Compared with controls Fgfr2(Mes-/-) embryos had increased common nephric duct length with no difference in apoptosis, indicating cranially displaced ureteral buds. Three-dimensional reconstruction at embryonic day 15.5 showed low ureteral insertion into the bladder near the bladder neck in Fgfr2(Mes-/-) mice. Postnatal Fgfr2(Mes-/-) mutants had a high rate of vesicoureteral reflux compared with controls (47.4% vs 4.0%, p = 0.00006). In postnatal mutants with unilateral reflux the refluxing ureters inserted closer to the bladder neck than nonrefluxing ureters. External ureteral insertional angles at the outer bladder wall formed by the ureteral insertion points and the bladder neck were greater in mutant refluxing ureters than in contralateral nonrefluxing ureters or control ureters. At embryonic day 15.5 Fgfr2 was decreased in Fgfr2(Mes-/-) kidneys compared with that in controls but not statistically different in ureters or bladders. CONCLUSIONS: Fgfr2(Mes-/-) mice have ureteral induction abnormalities associated with abnormal ureteral insertion in the bladder and subsequent vesicoureteral reflux, consistent with the Mackie and Stephens hypothesis. PMID- 20303522 TI - TRPA1 receptor induced relaxation of the human urethra involves TRPV1 and cannabinoid receptor mediated signals, and cyclooxygenase activation. AB - PURPOSE: We studied whether TRPA1 agonists interact with sensory and inflammatory signals to relax human urethral smooth muscle. MATERIALS AND METHODS: Urethral specimens were obtained perioperatively from 19 patients, and prepared for immunohistochemistry and functional experiments. The effects of allyl isothiocyanate, cinnamaldehyde and NaHS were studied in phenylephrine activated preparations combined with capsaicin, capsazepine, N omega-nitro-L-arginine, indomethacin or CP55940. RESULTS: TRPA1, cannabinoid 1 and cannabinoid 2 immunoreactivity was colocalized in nerve fibers of the human urethra. All TRPA1 agonists produced relaxation of phenylephrine contracted urethral preparations. Capsaicin increased relaxant responses to all TRPA1 agonists. It increased the mean +/- SEM -logIC50 of cinnamaldehyde and NaHS from 4.91 +/- 0.26 to 5.15 +/- 0.22 and 3.27 +/- 0.14 to 3.79 +/- 0.35, and the -logIC30 of allyl isothiocyanate from 3.11 +/- 0.24 to 3.41 +/- 0.26 (each p <0.05). Capsazepine in 5 preparations, indomethacin in 6 and CP55940 in 5 decreased cinnamaldehyde mediated relaxation by up to 39%, 88% and 89%, respectively. Nomega-nitro-L arginine and urothelial removal had no effect on relaxation by cinnamaldehyde in 5 preparations. CONCLUSIONS: Relaxation to TRPA1 agonists in human urethral preparations seem to work in cooperation with TRPV1 mediated signals, are negatively coupled via cannabinoid receptor activation and involve cyclooxygenase products. Urothelial TRPA1 signals may not be important to regulate normal human urethral smooth muscle tone. This does not exclude a role in the initiation of afferent activity normally and in disease states. PMID- 20303523 TI - Establishment and characterization of transplantable, luminescence labeled rat renal cell carcinoma cell lines. AB - PURPOSE: Since renal cell carcinoma is considered an immunogenic tumor, testing therapeutic strategies has been impeded by the lack of relevant tumor models in immunocompetent animals. Recent advances in bioluminescence imaging permit sensitive in vivo detection and quantification of cells emitting light. Thus, we established bioluminescent rat renal cell carcinoma cell lines for immunocompetent rats. MATERIALS AND METHODS: The rat renal cell carcinoma cell line ACI-RCC stemming from chemically induced renal cell carcinoma in syngeneic ACI rats was stably transfected with a recombinant retroviral vector encoding luciferase genes derived from fireflies (ACI-RCC-ffLuc) or click beetles (ACI-RCC cbLuc). Cell line growth patterns were characterized by bioluminescence imaging. RESULTS: Linear correlations noted observed between cell number and photon counts in each cell type. ACI-RCC-cbLuc emitted light about 500-fold higher than ACI-RCC ffLuc. When transplanted subcutaneously, only ACI-RCC-ffLuc grew, possibly because of less antigenicity. ACI-RCC-ffLuc photon emission correlated significantly with subcutaneous tumor size. Orthotopic tumor growth and subsequent metastatic spread were monitored with time by increased photon intensity on bioluminescence imaging. Based on ACI-RCC-cbLuc bioluminescent intensity the in vitro screening test allowed the identification of several anticancer agents, including molecules related to human renal cell carcinoma progression. CONCLUSIONS: The new in vivo rat renal cell carcinoma model with luciferase labeled tumor cells allowed us to monitor tumor growth noninvasively and semiquantitatively by bioluminescence imaging. This model system coupled with in vitro screening permits precise evaluation of tumor behavior in intact animals and determination of the therapeutic efficacy of anticancer agents for renal cell carcinoma. PMID- 20303525 TI - Emphysematous prostatitis in a diabetic patient. PMID- 20303526 TI - Compliance with antibiotic prophylaxis in children with vesicoureteral reflux: results from a national pharmacy claims database. AB - PURPOSE: Antibiotic prophylaxis is commonly used for medical management of vesicoureteral reflux. Little information exists on compliance with antibiotic prophylaxis in patients with vesicoureteral reflux. MATERIALS AND METHODS: We queried the i3 Innovus (Ingenix) pharmacy claims 2002 to 2007 database for patients 18 years old or younger with vesicoureteral reflux (ICD-9 code 593.7 plus claim for cystogram) and analyzed those with at least 1 year of followup data. Criteria for management with antibiotic prophylaxis were 2 or more 30-day supplies of antibiotic prescriptions, or 4 or more 14-day supplies of prescriptions if the antibiotic was a penicillin or cephalosporin. Antibiotic prophylaxis compliance was determined using a medication possession ratio, an estimate of the proportion of time that patients have a prescribed drug available for use. Compliance was established as a medication possession ratio of 80% or greater, meaning coverage with antibiotic prophylaxis for 80% of the year or more. RESULTS: Of 9,496 patients with vesicoureteral reflux 5,342 (56.3%) were treated with antibiotic prophylaxis. Most patients were female (81%) and 5 years old or younger (79%). Trimethoprims/sulfonamides were most commonly prescribed (62%) and antiseptics were next (24%). Of patients prescribed antibiotic prophylaxis 40% were compliant. Compliance was lower for 6 to 10-year-olds (OR 0.71, 95% CI 0.61-0.83) and 11 to 18-year-olds (OR 0.56, 95% CI 0.41-0.79) compared to younger children (5 years or less). Increased compliance was associated with 1 or more hospitalizations (OR 1.70, 95% CI 1.48-1.97) and 1 or more urologist visits (OR 1.41, 95% CI 1.25-1.58). CONCLUSIONS: Among patients with vesicoureteral reflux who are prescribed prophylactic antibiotics 40% are compliant with treatment. Young age, frequent hospitalization and specialist visits are associated with compliance. This knowledge may help to develop effective interventions to improve compliance and underscores the importance of reporting compliance in clinical studies evaluating the usefulness of antibiotic prophylaxis in vesicoureteral reflux management. PMID- 20303527 TI - Is staging beneficial for Fowler-Stephens orchiopexy? A systematic review. AB - PURPOSE: Fowler and Stephens showed that by dividing the spermatic vessels a high intra-abdominal testis could be placed in the scrotum. Testicular atrophy is a potential complication of this technique. We conducted a systematic review to determine whether single or 2-stage Fowler-Stephens orchiopexy results in better testicular viability. MATERIALS AND METHODS: We searched electronic databases, clinical trial registries and gray literature. We included reports describing boys younger than 18 years with a primary outcome of "testicular viability and position." We performed a meta-analysis using random effects models. Heterogeneity was assessed using forest plot and I(2) statistic. RESULTS: We identified 1,807 citations and included 61 articles. Single stage Fowler-Stephens orchiopexy was discussed in 9 articles, a 2-stage procedure in 36 and both approaches in 16. There were no randomized controlled trials, and most studies were cohort or case series. The pooled estimate of success rates was 80% for single stage Fowler-Stephens orchiopexy (95% CI 75 to 86) and 85% for 2-stage Fowler-Stephens orchiopexy (95% CI 81 to 90). The pooled odds ratio of single stage vs 2-stage Fowler-Stephens orchiopexy was 2.0 (95% CI 1.1 to 3.9) favoring the 2-stage procedure. There was no difference in the success rate between laparoscopic and open techniques in either single or 2-stage Fowler-Stephens orchiopexy. There was no evidence of asymmetry on the funnel plot. There were no complications reported with single stage, while ileus, hematoma and infection were the most common complications with 2-stage Fowler-Stephens orchiopexy. CONCLUSIONS: Both techniques have a fairly high success rate but 2-stage Fowler Stephens orchiopexy appears to carry a higher rate of success than the single stage approach (85% vs 80%, OR 2 in favor of 2-stage). Laparoscopic and open techniques had the same success rate. However, the level of evidence of the studies was low, and a study of a more robust design, such as a randomized controlled trial, should be performed. PMID- 20303528 TI - Editorial comment. PMID- 20303529 TI - Investigating contamination of phytotherapy products for benign prostatic hyperplasia with alpha-blockers and 5alpha-reductase inhibitors. AB - PURPOSE: Complementary and alternative medicine, including phytotherapeutic agents, or those derived from plant or herb extracts to treat symptoms, is widely accepted in the community. Men with bothersome lower urinary tract symptoms due to benign prostatic hyperplasia increasingly use such preparations. Phytotherapeutic agent quality is unregulated and in most instances the contents are unknown while erectile dysfunction and prostate cancer treatments have shown contamination with standard pharmaceuticals. Since trial results for benign prostatic hyperplasia phytotherapeutic agents are inconsistent, they may also be contaminated. Thus, we determined whether pharmacological doses of alpha-blockers and/or 5alpha-reductase inhibitors were present in a sample of phytotherapeutic agents for benign prostatic hyperplasia. MATERIALS AND METHODS: We analyzed 15 phytotherapeutic products marketed for benign prostatic hyperplasia. Only oral tablets or capsules were considered with teas, tonics and foods excluded from study. We made random purchases from shop front health stores and Internet retailers. All batches of commercial phytotherapy were analyzed by high performance liquid chromatography. Analysis was semiquantitative using extracts from alfuzosin, doxazosin, terazosin, tamsulosin, dutasteride and finasteride. RESULTS: In the 15 batches of different phytotherapeutic agents tested no interference secondary to contamination with alpha-blockers or 5alpha-reductase inhibitors was observed. CONCLUSIONS: All phytotherapeutic agents for benign prostatic hyperplasia in this study tested negative for alpha-blockers and 5alpha reductase inhibitors. Inconsistent results in trials using phytotherapeutic agents are probably not explained by the presence of standard pharmaceuticals. PMID- 20303531 TI - Medical malpractice claims risk in urology: an empirical analysis of patient complaint data. AB - PURPOSE: Patient complaints are associated with physician risk management experience, including medical malpractice claims risk, and small proportions of physicians account for disproportionate shares of claims. We investigated whether patient complaint experience differs among urologists, and whether urological subspecialists generate distinct quantities and types of complaints. MATERIALS AND METHODS: This retrospective study examined 1,516 unsolicited patient complaints filed against 268 urologists. Patient complaint and urological subspecialty data were collected from January 1, 2004 through December 31, 2007 for 15 geographically diverse health systems. The cohort urologists were assigned medical malpractice claims risk scores and complaint type profiles. A weighted sum algorithm produced risk scores from 4 consecutive years of complaint data and complaint type profiles were generated using a standardized coding system. Statistical analyses tested the associations among risk score, complaint type profile and urological subspecialty. Complaint type profile and subspecialty distribution were assessed for urologists in the cohort top decile for risk scores. RESULTS: Overall 125 (47%) urologists were associated with 0 patient complaints, while 30 (11%) urologists were associated with 758 (50%) of the patient complaints. Subspecialty and distribution of risk scores were significantly associated (p <0.001). Calculi and oncology subspecialist distributions suggest greater overall risk. Complaint types also varied among subspecialists (p = 0.02). There was no association between top decile urologists and complaint type profile (p = 0.19). CONCLUSIONS: Unsolicited patient complaints were nonrandomly distributed among urologists and urological subspecialties. Monitoring patient complaints may allow for early identification of and intervention with high risk urologists before malpractice claims accumulate. PMID- 20303530 TI - Expression of pluripotent stem cell reprogramming factors by prostate tumor initiating cells. AB - PURPOSE: We identified a discrete population of stem cell-like tumor cells expressing 5 essential transcription factors required to reprogram pluripotency in prostate tumor cell lines and primary prostate cancer tissue. MATERIALS AND METHODS: DU145 and PC3 human prostate cancer cell lines (ATCC), tumor tissue from patients with prostate cancer and normal prostate tissue were evaluated for the reprogramming factors OCT3/4 (Cell Signaling Technology), SOX2, Klf4 (Santa Cruz Biotechnology, Santa Cruz, California), Nanog (BioLegend) and c-Myc (Cell Signaling) by semiquantitative reverse transcriptase-polymerase chain reaction, histological and immunohistochemical analysis. Stem cell-like tumor cells were enriched by flow cytometric cell sorting using E-cadherin (R&D Systems) as a surface marker, and soft agar, spheroid and tumorigenicity assays to confirm cancer stem cell-like characteristics. RESULTS: mRNA expression of transcription factors OCT3/4 and SOX2 highly correlated in primary prostate tumor tissue samples. The number of OCT3/4 or SOX2 expressing cells was significantly increased in prostate cancer tissue compared to that in normal prostate or benign prostate hyperplasia tissue (p <0.05). When isolated from the DU145 and PC3 prostate cancer cell lines by flow cytometry, stem cell-like tumor cells expressing high OCT3/4 and SOX2 levels showed high tumorigenicity in immunodeficient mice. In vivo growth of the parental DU145 and PC3 prostate cancer cell lines was inhibited by short hairpin RNA knockdown of OCT3/4 or SOX2. CONCLUSIONS: Data suggest that prostate tumor cells expressing pluripotent stem cell transcription factors are highly tumorigenic. Identifying such cells and their importance in prostate cancer growth could provide opportunities for novel targeting strategies for prostate cancer therapy. PMID- 20303532 TI - Six-transmembrane epithelial antigen of the prostate as an immunotherapeutic target for renal cell and bladder cancer. AB - PURPOSE: T-cell based immunotherapy for renal cell and bladder cancer is one of the most promising therapeutic approaches. STEAP is a novel cell surface protein that is over expressed in various cancers, including renal cell and bladder cancer. Recently we induced STEAP specific helper T lymphocytes that recognize the naturally processed STEAP peptide epitopes STEAP(102-116) and STEAP(192-206) arising from STEAP expressing tumor cells. Thus, STEAP may be a useful tumor associated antigen for designing T-cell based immunotherapy. We determined whether STEAP could induce anti-cellular immune responses to urological cancer. MATERIALS AND METHODS: We selected 2 previously described STEAP derived epitope peptides, STEAP(102-116) and STEAP(192-206), and examined their ability to elicit helper T-lymphocyte responses by in vitro vaccination of CD4 T lymphocytes from healthy individuals and patients with cancer. RESULTS: STEAP peptides induced helper T-lymphocyte responses using lymphocytes from healthy individuals that directly recognized STEAP expressing, DR positive renal cell and bladder cancer cells, and autologous dendritic cells pulsed with STEAP expressing tumor cell lysates in a major histocompatibility complex class II restricted manner. These peptides also stimulated T-cell responses in patients with renal cell or bladder cancer. Each STEAP peptides behaved as a promiscuous T-cell epitope, in that they stimulated T cells in the context of multiple major histocompatibility complex class II alleles. CONCLUSIONS: Results show that STEAP helper T-lymphocyte epitopes could be used to optimize T-cell based immunotherapy against STEAP expressing renal cell and bladder cancer. PMID- 20303534 TI - Percutaneous cystolithotomy for calculi in reconstructed bladders: initial UCLA experience. AB - PURPOSE: Following bladder augmentation, patients are at significant risk for bladder calculi. We present our experience with a minimally invasive treatment approach using endoscopically assisted percutaneous cystolithotomy. MATERIALS AND METHODS: A retrospective chart review identified 74 patients who underwent percutaneous cystolithotomy following bladder augmentation between 2002 and 2009. Cystogram was performed to determine the ideal location for percutaneous bladder access and a guidewire was inserted in the bladder through a bile needle. A balloon dilator was used to place a 30Fr sheath. Rigid cystoscopy with a 26Fr nephroscope allowed stone treatment by basketing and ultrasonic lithotripsy. A suprapubic 22Fr catheter was then placed. Patients were seen on postoperative day 14 and abdominal ultrasound was performed. If no significant residual calculi were visualized, the suprapubic tube was removed. RESULTS: Mean +/- SD patient age at operation was 20 +/- 10.7 months (range 4 to 40). Mean +/- SD time between bladder augmentation and percutaneous cystolithotomy was 4.8 +/- 2.05 years. Of the patients 38 (51%) were male and 36 (49%) were female. Mean +/- SD number of stones per patient was 4.6 +/- 7.8 (range 1 to 60). Ultrasonic lithotripsy was performed in 49 cases (66%). In 25 cases (34%) only stone basketing was performed. A total of 70 patients (95%) were stone-free on abdominal plain film at 14 days. Of the procedures 24 (32%) were performed on an outpatient basis and 50 were performed on an inpatient basis with a mean +/- SD hospital stay of 1.3 +/- 2.7 days (range 1 to 21). There were 9 minor complications noted (12%). CONCLUSIONS: Endoscopic percutaneous cystolithotomy offers a safe and effective treatment option for bladder calculi in reconstructed bladders and is the preferred method at our institution. PMID- 20303535 TI - Editorial comment. PMID- 20303536 TI - Minimizing pain during vasectomy: the mini-needle anesthetic technique. AB - PURPOSE: We describe pain scores for a modified anesthesia technique for no scalpel vasectomy using a 1-inch 30 gauge mini-needle. MATERIALS AND METHODS: A prospective study was performed in 277 patients who received anesthesia using a 3 cc syringe filled with approximately 2 cc 2% lidocaine without epinephrine and a 1-inch 30 gauge needle. Local anesthesia was given directly to the vas at the expected surgical site on each side. RESULTS: Mean +/- SD pain intensity score on the 10 cm visual analog scale was 1.5 +/- 1.6 (95% CI 1.3-1.7) during the anesthesia and 0.6 +/- 1.0 (95% CI 0.5-0.7) during the procedure. Patients experienced less pain during anesthesia and the procedure than they expected before vasectomy (average 3.1 +/- 1.8, 95% CI 2.8-3.3). CONCLUSIONS: The mini needle technique provides excellent anesthesia for no-scalpel vasectomy. It compares favorably to the standard vasal block and other anesthetic alternatives with the additional benefit of minimal equipment and less anesthesia. PMID- 20303537 TI - Value of ultrasound in evaluation of infants with first urinary tract infection. AB - PURPOSE: We evaluated the role of ultrasound in diagnosing and treating infants with a first urinary tract infection with a focus on important structural abnormalities. MATERIALS AND METHODS: In a setting of limited prenatal ultrasound screening this population based, prospective, 3-year study included 161 male and 129 female infants. Ultrasound and dimercapto-succinic acid scintigraphy were performed as initial investigations and voiding cystourethrography was conducted within 2 months. RESULTS: Ultrasound revealed dilatation in 15% of patients and increased kidney length in 28%. Sensitivity for detecting scintigraphic abnormality was 48%. Renal length was significantly correlated to inflammatory parameters, including scintigraphic abnormalities. Important structural abnormalities were detected in 40 cases, with 30 on ultrasound, while 10 of 27 cases of dilating reflux (mostly grade III) were missed. Outside the study there were 28 additional cases of structural abnormality, of which 15 were detected prenatally. CONCLUSIONS: Ultrasound detected most structural abnormalities except grade III reflux. Since it is noninvasive, ultrasound has a place in the evaluation of infants with urinary tract infection, especially in the absence of prenatal ultrasound during late pregnancy. Kidney length in infants with acute infection correlated with inflammatory parameters, and the clinical importance of this finding needs to be studied further. PMID- 20303538 TI - Clinical implications of TMPRSS2-ERG gene fusion expression in patients with prostate cancer treated with radical prostatectomy. AB - PURPOSE: Molecular prognostic factors may be useful tools for prostate cancer that complement classic clinicopathological factors. Genetic rearrangements between TMPRSS2 and ETS have been described for prostate cancer but their clinical significance is still unclear. We analyzed the association of the TMPRSS2-ERG fusion gene with prostate cancer outcome in patients treated with radical prostatectomy. MATERIAL AND METHODS: We analyzed prostate cancer samples from 226 patients treated with radical prostatectomy from 1996 to 2002 with a median followup of 84 months (range 9 to 153). TMPRSS2-ERG fusion gene expression was determined by reverse transcriptase-polymerase chain reaction. Clinicopathological and molecular variables were related to biochemical and clinical progression-free survival by the Kaplan-Meier proportional risk log rank test. A Cox proportional hazards model using stepwise selection was used to identify independent predictors of poor outcome. RESULTS: TMPRSS2-ERG fusion was detected in 114 cases (50.4%). We noted no association between fusion gene status and prostate cancer clinicopathological characteristics. However, when patients were grouped by TMPRSS2-ERG fusion gene status, different clinicopathological prognostic factors defined each group for biochemical and clinical progression free survival. Prostate specific antigen, specimen Gleason score and margin status were independent prognostic factors in patients with prostate cancer expressing the fusion gene. In the nonexpressing TMPRSS2-ERG group the prognostic factors were cT, Gleason score and margins. CONCLUSIONS: TMPRSS2-ERG fusion gene status classifies patients with prostate cancer treated with radical prostatectomy into groups defined by different prognostic factors. This could be the basis for designing more refined treatment strategies. PMID- 20303539 TI - Hypertrophic lagoon management by sediment disturbance. AB - Experimental control of eutrophication in a small coastal lagoon was attempted by means of sediment disturbance. A specially designed boat was used to resuspend the top 3 cm of sediment by a jets of air-water directed towards the bottom. This disturbance was carried out for 3 months in each of two areas with a surface area of 24 and 20 hectares respectively. In a total of 80 stations in these two areas and in two undisturbed areas of 16 and 20 ha, organic matter, porosity, density and redox potential were monitored in sediment bimonthly and free sulphides were monitored in water close to the bottom. Before, during and after disturbance, the impact of daily sediment resuspension on the water column was monitored monthly, as ammonium nitrogen (N-NH4), soluble reactive phosphorus (SRP), dissolved oxygen (DO) and pH. In the whole lagoon, sediment texture was determined at the start and at the end of the experiment in 120 stations, and seaweed (mainly Chaetomorpha linum and Lophosiphonia subadunca) and seagrass (Ruppia cirrhosa) biomasses were estimated in 42 stations every month. The results showed a stable organic matter content in disturbed areas and an increase in undisturbed areas, as well as an increase in seaweed in areas distant from disturbed areas. No significant effect of sediment resuspension on water column N-NH4, SRP, DO or pH was found. PMID- 20303540 TI - Does ecological energetics lead to trophic competition in juvenile fish? A case study from the Vistula Lagoon (southern Baltic Sea). AB - Production, respiration, egestion of faeces and excretion of ammonia were measured in competing early developmental stages of fish species (herring, smelt, perch and stickleback) to calculate their daily energy (food) requirements in the Vistula Lagoon, southern Baltic Sea. The highest consumption (per capita and per unit body mass) was found in perch and European smelt, and the lowest in herring. However, young herring had the highest contribution to the exploitation of food resources because of their dominance in the Lagoon. The coefficient of assimilation efficiency U(-1) and coefficient of the utilization of assimilated energy for growth K2 also had the highest values in this species. PMID- 20303541 TI - [Multiple chemical sensitivity: epidemiological, clinical and prognostic differences between occupational and non-occupational cases]. AB - BACKGROUND AND OBJECTIVE: The progressive increase in cases of multiple chemical sensitivity (MCS) syndrome and the lack of studies which associate the syndrome with possible occupational origins means that further research in this field is required. The objective of this study was to compare the epidemiological, clinical and prognostic aspects of cases of MCS of occupational and non occupational origin. PATIENTS AND METHOD: Observational study of patients diagnosed with MCS by the toxicology outpatients clinic of the Hospital Clinic of Barcelona between 2002 and 2007. The occupational and non-occupational origin of MCS was considered as an independent variable. The dependant variables were occupational activity, triggering agents of MCS, chemical agents associated with the development of clinical manifestations, severity of the symptoms, comorbidities and work disability. Percentages were compared between groups. RESULTS: A total of 165 patients were included: The mean age was 47.7 years and 90.9% were women. There were significant differences between patients of occupational and non-occupational origin with respect to comorbidities such as chronic fatigue syndrome (68.1% versus 88.5%; p=0.002) and fibromyalgia (49.3% versus 73.9%; p=0.002), temporary disability (60.9% versus 39.6%; p=0.006) and permanent disability (8.7% versus 22.9%; p=0.006). CONCLUSIONS: Cases of MCS attributed to an occupational origin had fewer comorbidities and less permanent disability than those of non-occupational origin. PMID- 20303542 TI - [Quality of the antiretrovirals drug interactions database]. AB - BACKGROUND AND OBJECTIVE: To identify antiretrovirals drug interaction databases (ADID) and evaluate its structural quality. MATERIAL AND METHOD: A literature search in Medline and a grey literature search were conducted. The identified ADID underwent scrutiny based on exclusion criteria and structural quality (4 minimum quality criteria: stratification by level of severity, classification by level of evidence, bibliographic data, description of the clinical management) and 11 criteria that provide the relative importance (specific weight). We analyzed the degree of compliance of the criteria in each ADID and the degree of compliance of each criterion in all ADID. RESULTS: We identified 81 databases but only 8 of them were included for the analysis. Only 3 of them reached the minimum criteria: HIV-Drug interactions, Clinical Care Options HIV (The Drug-Drug Interactions Tool) and InteraccionesHIV.com. All the databases included are presented on computerized support, organized by active drug and describe clinical management; 7 of them inform about the interaction mechanism of action and have multicheck structure that speeds up the search; 4 declare they have no conflict of interest and stratifies by level of severity; 5 contain bibliographic reference; none of them classifies by level of evidence. CONCLUSIONS: There are many antiretroviral interaction databases available. The knowledge about their quality structure will help provide appropriate information. PMID- 20303543 TI - [Black hairy tongue]. PMID- 20303544 TI - [New human retrovirus]. PMID- 20303545 TI - [Treatment guidelines for hyperglycaemia in type 2 diabetes patients with stable chronic heart failure or ischemic cardiomyopathy without heart failure]. PMID- 20303546 TI - [Analysis of the implementation of a Joint Accreditation Committee of the International Society for Cellular Therapy and European Group for Blood and Marrow Transplantation acreditation in a clinical program of hematopoietic progenitor cell transplantation]. PMID- 20303547 TI - [Butterfly cutaneous lesion]. PMID- 20303548 TI - [Descriptive anatomy of the orbit]. AB - Anatomical description of the orbit is essential for an accurate understanding of its related tumoral pathologies. Numerous cadaveric pictures illustrate this chapter, which contains the description of the bony walls of the orbit and its muscular nerve, and vascular structures. PMID- 20303549 TI - [Conclusion]. PMID- 20303550 TI - [Malignant extraconal tumors of the orbit in childhood]. AB - Malignant extraconal orbital tumors are very rare during childhood and must be referred as soon as possible to a highly specialized center to be managed by a multidisciplinary team. They are often referred on an emergency basis. Both diagnosis and treatment must be undertaken as soon as possible. The course of these malignant tumors can be acute and can jeopardize the function of the eye or be life-threatening, especially in the event of metastatic locations. Extra-axial proptosis is by far the most frequent revealing symptom. Local and general examinations are of utmost importance. Sometimes diagnosis should be clear with the association of an orbital tumor and deterioration of the general health status favoring metastatic disease. Most metastatic neuroblastomas present such clinical symptoms in young children. Today both CT and MRI are highly valuable in assessing the diagnosis and starting the management of these tumors. Biopsy is mandatory to confirm the diagnosis. It can be reinforced by molecular biology. Among the primitive tumors, soft tissue sarcomas, especially rhabdomyosarcomas, are the most frequent. The diagnosis is suggested when the onset of the disease is acute and the course is rapid. Most respond to neoadjuvant chemotherapy. In the event of a residual tumor, local treatment is indicated so that surgery and/or radiotherapy are used as second-line treatment. Prognosis is closely related to histology. It can be satisfactory (Langerhans' cell histiocytosis, lymphoma, meningioma, infantile fibrosarcoma) or poor (metastatic tumor, rhabdoid tumor). PMID- 20303551 TI - [Congenital orbital tumors in adults (dermoid cysts)]. AB - The most frequent intraorbital congenital tumors are dermoid cysts, which account for 2-9% of all orbital tumors. Teratomas are also congenital tumors but occur only in children. The revealing clinical sign is a subcutaneous mass along the superior orbital rim if the cyst is superficial or proptosis if the cyst is deep. Neuroradiological work-up provides the preoperative diagnosis. The treatment is solely surgical. PMID- 20303552 TI - [Primary bone tumors of the orbit]. AB - Primary orbital bone tumors account for 0.6-2% of all orbital tumors. This is a heterogeneous group of tumors arising from osseous, cartilaginous, fibrous, and vascular tissues. The two most commonly encountered lesions are fibrous dysplasia and osteoma. Treatment of the primitive orbital bone tumors is generally surgical. PMID- 20303553 TI - [Optic nerve glioma in children]. AB - Optic pathway gliomas are rare tumors accounting for 3-5% of brain tumors in children; 90% are observed in children. They account for 4% of orbital tumors in children. Association with NF 1 is classical and the incidence of NF 1 in patients with optic pathway gliomas is estimated at 30-58%. Usually these tumors are pilocytic astrocytomas and their regression, particularly in patients with NF 1, has been described. Exophthalmos and loss of visual acuity or blindness are the usualpresentation in progressive disease. CT and above all MRI study of the orbit and the brain are necessary to make a complete evaluation of the disease. Gross total removal of the tumor provides 100% cure, but surgery can be proposed only for growing tumor with severe exophthalmos and no useful field of view or blindness. Chemotherapy must be proposed as first-line treatment for growing tumor with moderate exophthalmos and useful vision when the tumor is strictly confined in the orbit. The place of radiotherapy for pure intraorbital gliomas has not been defined and proton beam therapy has to be evaluated. PMID- 20303554 TI - [Vascular tumors of the orbit]. AB - Vascular tumors of the orbit include capillary hemangioma, cavernous hemangioma, hemolymphangioma, hemangiopericytoma and a few rare tumors. Capillary hemangioma and hemolymphangioma, occurring mainly in children, are covered in the chapter devoted to childhood tumors. In this chapter, cavernous hemangioma and hemangiopericytoma are discussed as well as rare vascular tumors. Although orbital varix is not a tumor, it is also considered because of the diagnostic problems and the close correlation of orbital varix with a true tumor: hemolymphangioma. PMID- 20303555 TI - [Orbital tumors in children: clinical examination, imaging, specific progression]. AB - "Orbital tumors (OT) are neoplasms of the bony orbit and contents except for the eyeball." Given this definition, we exclude the retinoblastomas, which are the most frequent tumors of this anatomical area in the pediatric population. Although these tumors are rare, there is a great variety of etiologies. Among them, the most frequent OTs in childhood are rhabdomyosarcomas and metastatic tumors: metastatic neuroblastomas and leukemias (chloromas). Moreover, adult and pediatric varieties of OT are made up of two clusters of distinctive histological entities. Examination must be careful: measurement, direction of proptosis, impairment of ocular motility, compressive optic neuropathy, strabismus, etc. Age at onset as well as unilateral or bilateral proptosis are important features. Benign tumors such as dermoid cysts or hemangiomas grow slowly, whereas rapid growth suggests a malignant tumor. Fundi and visual acuity should be checked. The general examination focuses especially on cutaneous abnormalities such as cafe au lait spots and subcutaneous nodules in neurofibromatosis type 1 (NF1), a hemangioma that often involves the cutaneous portion of the eyelid. When a metastatic tumor is suspected, abdominal palpation and ultrasonography must be performed. Ultrasonography leaves the posterior third of the orbit inaccessible to exploration. The depth to which it can penetrate the orbit is limited (20mm). Most of the time, standard x-rays, CT, and MR imaging allow for an adequate assessment and usually provide a diagnosis. In children, CT and MRI sometimes require anesthesia to be properly performed. PMID- 20303556 TI - [Neurosurgical approaches to the orbit]. AB - Surgical approaches to the orbit differ depending on the surgical specialty. Neurosurgical approaches consider the posterior two-thirds of the orbit and can be summed up as the superior, lateral, and superolateral approaches. Orbital rim removal enlarges the exposure when necessary. Each neurosurgical approach is described in this chapter. Schematically, subfrontal approaches are used to reach the inner quadrant orbital tumors and the others to access external quadrant tumors. Nevertheless, the choice of the approach is discussed regarding to the presumed pathologic preoperative diagnosis. PMID- 20303557 TI - [Sphenoorbital meningiomas]. AB - Sphenoorbital meningiomas account for 20% of all orbital tumors treated by neurosurgeons. Proptosis is the main clinical sign but this can be reduced with accurate surgical management. Complete tumor removal is often difficult considering the frequent extensions of the meningioma to the superior orbital fissure, the cavernous sinus, and the periorbita. PMID- 20303558 TI - [Orbital tumors: the ophthalmologist's point of view (biopsies - approaches - exenteration)]. AB - This publication details the indications and contraindications of orbital tumor biopsies and surgical removal. Until now biopsies of pleomorphic adenomas were contraindicated. This management is now being reconsidered. Contrary to past convention, for suspected malignant tumors, a biopsy is essential. Great caution is required in surgery of inflammatory pseudotumors. Surgery is not recommended in lymphomas. PMID- 20303559 TI - [Diagnostic imaging of liposclerosing myxofibrous tumor of bone]. AB - Liposclerosing myxofibrous tumor of bone is a benign lesion with a complex histologic structure. Its origin is uncertain, although it seems to be related to intraosseous lipomas and fibrous dysplasia, and it is sometimes impossible to distinguish from these two entities. It is usually located in the intertrochanteric region of the femur. Radiologically, it is a well-defined lytic lesion with sclerotic margins and high signal intensity in T2- weighted MR images. We present two cases with radiologic characteristics and location compatible with liposclerosing myxofibrous tumor of bone. In one case, PET studies suggested a malignant lesion. The diagnosis can be established on the basis of the radiological characteristics and location of the lesion: PET and histologic examination can sometimes lead to the wrong diagnosis. PMID- 20303560 TI - Chagas' disease and HIV co-infection in patients without effective antiretroviral therapy: prevalence, clinical presentation and natural history. AB - The objectives of this study were to establish the prevalence of Chagas' disease among HIV seropositive patients and to define the clinical profile of co-infected cases. Cross-sectional study: the prevalence of co-infected subjects was 1.3% and there was no significant difference between co-infected and non co-infected patients relative to race, birthplace, home address and CD4 T cells. The co infected group comprised predominantly women and mean age and median viral load were higher. Longitudinal study: included 20 patients (12 women) and described the clinical presentation and natural history of concomitant infections. The mean follow-up time was 35.8 months, mean age was 43+/-8.7 years and 60% of patients were white. During the follow-up, a total of 113 serological tests for Chagas' disease were performed: 89 (78.8%) were reactive/positive, 21 (18.6%) were doubtful and three (2.6%) were non-reactive/negative. Positive results for xenodiagnosis were high (81%). At the baseline evaluation, thirteen patients had the indeterminate form of Chagas' disease and seven cardiopathy. One patient developed from indeterminate to digestive form, three had a reactivation of Chagas' disease in the central nervous system, all had parasitological confirmation and received specific treatment. There were 11 deaths. Thus, HIV infected patients should be tested for Chagas' disease when epidemiologically relevant. PMID- 20303561 TI - Identification of light and dark hypertrophic chondrocytes in mouse and rat chondrocyte pellet cultures. AB - Hypertrophic "light" and "dark" chondrocytes have been reported as morphologically distinct cell types in growth cartilage during endochondral ossification in many species, but functional differences between the two cell types have not been described. The aim of the current study was to develop a pellet culture system using chondrocytes isolated from epiphyseal cartilage of neonatal mice and rats, for the study of functional differences between these two cell types. Hypertrophic chondrocytes resembling those described in vivo were observed by light and electron microscopy in sections of pellets treated with triiodothyronine, 1% fetal calf or mouse serum, 10% fetal calf serum or 1.7MPa centrifugal pressure at day 14, and in pellets cultured with insulin or 0.1% fetal calf or mouse serum at day 21. A mixed population of light and dark chondrocytes was found in all conditions leading to induction of chondrocyte hypertrophy. This rodent culture system allows the differentiation of light and dark chondrocytes under various conditions in vitro and will be useful for future studies on tissue engineering and mechanisms of chondrocyte hypertrophy. PMID- 20303564 TI - Modelling reactive CAH transport using batch experiment degradation kinetics. AB - Models describing transport of degradable organic substances in a porous medium require parameters of the biodegradation kinetics that can be obtained from batch degradation assays. It is rarely assessed if liquid batch biodegradation rates allow extrapolation to reactive transport in a porous medium, i.e. if the cell specific activity in a porous medium with flow-through is identical to that of pelagic cells in liquid cultures. Failure of model predictions can be used to identify the rate-limiting processes in the reactive transport. Column data of anaerobic trichloroethene (TCE) transport and degradation at three flow rates were predicted with a model using biodegradation kinetics derived from a liquid culture. The extent of dechlorination at the column outlet was very well predicted within a factor 1.4 if the specific microbial biomass in the columns was used as an input parameter. This suggests that potential mass transfer limitations in biofilms or differences in microbial ecology between batch and column had minor effects on dechlorination. The model was subsequently extended with Monod kinetics to predict both biomass growth and chlorinated aliphatic hydrocarbon (CAH) degradation in the columns using liquid batch data. These models largely overestimated CAH dechlorination unless microbial transport with cell elution was included and unless a slight batch to column adjustment was made to better predict microbial biomass. With 4 adjustable parameters the model succeeded in predicting the microbial numbers within a factor 4.3 and the extent of dechlorination within a factor 1.2. Our analysis validates the batch to column extrapolation for this dedicated set-up provided that the microbial biomass in columns is well predicted. The sensitivity analysis shows that the extent of dechlorination in the reactive transport is most sensitive to the parameters of TCE degradation kinetics, including microbial growth followed by the residence time. PMID- 20303562 TI - Correction of a carboxyl terminal simian immunodeficiency virus Nef frameshift mutation restores virus replication in macaques. AB - Previous studies demonstrated that the nef gene is a critical determinant of the pathogenicity of simian immunodeficiency virus (SIV) in macaques. In the present study, we evaluated the effect of a spontaneous frameshift mutation in the C terminus of the nef gene of the minimally pathogenic SIVsmH4i clone. This clone exhibited a single nucleotide deletion in the nef gene relative to pathogenic SIV clones that resulted in a frameshift and addition of 46 amino acids to the C terminus of Nef. We generated a corrected version of this clone, SIVsmH4i Nef+ that restored Nef protein expression. Inoculation of macaques with SIVsmH4i resulted in delayed and low levels of peak viremia. This contrasted with improved kinetics and robust peak viremia in macaques inoculated with the corrected version. Despite the restoration of in vivo replication ability, neither clone resulted in memory CD4+ T cell loss or disease in a period of two years. PMID- 20303563 TI - Substitution of lysine at 627 position in PB2 protein does not change virulence of the 2009 pandemic H1N1 virus in mice. AB - A lysine at the 627 position (627K) of PB2 protein of influenza virus has been recognized as a determinant for host adaptation and a virulent element for some influenza viruses. While seasonal influenza viruses exclusively contained 627K, the pandemic (H1N1) 2009 possessed a glutamic acid (627E), even after circulation in humans for more than 6months. To explore the potential role of E627K substitution in PB2 in the pandemic (H1N1) 2009 virus, we compared pathogenicity and growth properties between a recombinant virus containing 627K PB2 gene and the parental A/California/4/2009 strain containing 627E. Our results showed that substitution of 627K in PB2 gene does not confer higher virulence and growth rate for the pandemic (H1N1) 2009 virus in mice and cell culture respectively, suggesting 627K is not required for human adaptation of the pandemic (H1N1) 2009 virus. PMID- 20303565 TI - Combined (alkaline+ultrasonic) pretreatment effect on sewage sludge disintegration. AB - The individual effects of alkaline (pH 8-13) and ultrasonic (3750-45,000kJ/kg TS) pretreatments on the disintegration of sewage sludge were separately tested, and then the effect of combining these two methods at different intensity levels was investigated using response surface methodology (RSM). In the combined pretreatment, ultrasonic treatment was applied to the alkali-pretreated sludge. While the solubilization (SCOD/TCOD) increase was limited to 50% in individual pretreatments, it reached 70% in combined pretreatment, and the results clearly showed that preconditioning of sludge at high pH levels played a crucial role in enhancing the disintegration efficiency of the subsequent ultrasonic pretreatment. By applying regression analysis, the disintegration degree (DD) was fitted based on the actual value to a second order polynomial equation: Y= 172.44+29.82X(1)+5.30x10(-3)X(2)-7.53x10(-5)X(1)X(2)-1.10X(1)(2)-1.043x10( 7)X(2)(2), where X(1), X(2), and Y are pH, specific energy input (kJ/kg TS), and DD, respectively. In a 2D contour plot describing the tendency of DD with respect to pH and specific energy input, it was clear that DD increased as pH increased, but it seemed that DD decreased when the specific energy input exceeded about 20,000kJ/kg TS. This phenomenon tells us that there exists a certain point where additional energy input is ineffective in achieving further disintegration. A synergetic disintegration effect was also found in the combined pretreatment, with lower specific energy input in ultrasonic pretreatment yielding higher synergetic effect. Finally, in order to see the combined pretreatment effect in continuous operation, the sludge pretreated with low intensity alkaline (pH 9)/ultrasonic (7500kJ/kg TS) treatment was fed to a 3 L of anaerobic sequencing batch reactor after 70 days of control operation. CH(4) production yield significantly increased from 81.9+/-4.5mL CH(4)/g COD(added) to 127.3+/-5.0mL CH(4)/g COD(added) by pretreatment, and this enhanced performance was closely related to the solubilization increase of the sludge by pretreatment. However, enhanced anaerobic digestion resulted in 20% higher soluble N concentration in the reactor, which would be an additional burden in the subsequent nitrogen removal system. PMID- 20303566 TI - Total and methyl mercury transformations and mass loadings within a wastewater treatment plant and the impact of the effluent discharge to an alkaline hypereutrophic lake. AB - Concerns over the fate and bioaccumulation of mercury (Hg) inputs to Onondaga Lake, a hypereutrophic lake in central New York, prompted an investigation into the concentrations and fluxes of Hg discharge from the Onondaga County Metropolitan Wastewater Treatment Plant (METRO WWTP). Discharge of methyl Hg (MeHg) is of concern because it is the form of Hg that readily bioaccumulates along the aquatic food chain. This study incorporated clean protocols for sampling and Hg analysis to evaluate: seasonal patterns in the concentrations of total Hg (THg) and MeHg in the WWTP unit processes; the production of MeHg within the unit processes of the WWTP; the overall fate of THg and MeHg within the WWTP; and the relative impact of the Hg discharged from the WWTP to Onondaga Lake. Concentrations of THg (range: 80-860 ng/L) and MeHg (0.7-17 ng/L) in raw sewage were highly variable, with higher concentrations observed in the summer months. The dynamics of THg though the WWTP were correlated with total suspended solids (TSS). As a result, the majority of the THg removal (55%) occurred during primary treatment. Overall, about 92% of the THg entering the plant was removed as sludge, with volatilization likely a minor component of the overall Hg budget. The transformation of MeHg through the plant differed from THg in that MeHg was not correlated with TSS, and displayed strong seasonal differences between winter (November to April) and summer (May-October) months. During the summer months, substantial net methylation occurred in the activated sludge secondary treatment, resulting in higher MeHg concentrations in secondary effluent. Net demethylation was the dominant mechanism during tertiary treatment, resulting in removal of substantial MeHg from the secondary effluent. The overall MeHg removal efficiency through the plant was about 70% with more efficient removal during summer months. Sediment trap collections made below the epilimnion of Onondaga Lake indicated average deposition rates of 12 microg/m(2)-day for THg and 0.33 microg/m(2)-day for MeHg. These deposition rates are more than an order of magnitude higher than the thermocline area normalized external loads from METRO effluent (0.85 microg/m(2)-day for THg, 0.05 microg/m(2)-day for MeHg). Our findings indicate that the impact of the discharge from METRO is relatively small, contributing about 10-15% of Hg to the total gross Hg input to the hypolimnion of the lake. PMID- 20303567 TI - In situ remediation of metal-contaminated soils with organic amendments: role of humic acids in copper bioavailability. AB - The purposes of this study were to determine the Cu(II) binding behavior of humic acids (HAs) isolated from biosolid compost (BI), leonardite (LE), a metal contaminated soil, and the soil remediated with either BI or LE in relation to their structural properties, and to explore the role exerted by the HA fractions in controlling soil Cu(II) bioavailability. Potentiometric titrations at pH 5 and ionic strength 0.1M and the Langmuir model were used to obtain the Cu(II) complexing capacity of the HAs examined and the conditional stability constant of the Cu(II)-HA complexes. The Cu(II) complexing capacity increased as the content of acidic ligands, especially COOH groups, aromaticity, and humification degree increased, following the order BI-HA -2.0). Zoledronic acid infusion was well tolerated and without substantial renal toxicity. CONCLUSIONS: Zoledronic acid improves BMD in men with M0 CaP on ADT with severe osteopenia or osteoporosis (T scores < 2.0). This novel finding identifies a high-risk patient population that can potentially benefit from bisphosphonate therapy. PMID- 20303575 TI - A survey of primary care physician practices in the diagnosis and management of women with interstitial cystitis/painful bladder syndrome. AB - OBJECTIVES: To describe the practice patterns among primary care physicians' (PCPs) managing patients with symptoms suggestive of interstitial cystitis/painful bladder syndrome (IC/PBS). METHODS: We developed a clinical vignette describing a woman with typical IC/PBS symptoms to elicit questions about etiology, management strategies, and familiarity with this syndrome. We mailed the questionnaire to 556 PCPs, including academicians and community physicians, in Boston, Los Angeles, and Chicago. RESULTS: We received 290 completed questionnaires (response rate, 52%). Nineteen percent of respondents reported they had "never" seen a patient like the one described in the vignette. Two-thirds of respondents correctly identified the hallmark symptom of IC/PBS (bladder pain/pressure). Regarding etiology, 90% correctly indicated that IC/PBS was a noninfectious disease, 76% correctly reported that it was not caused by a sexually transmitted infection, and 61% correctly indicated that it was not caused by a psychiatric illness. Common treatments included antibiotics and nonsteroidal anti-inflammatory agents. Referrals were often made to a specialist. CONCLUSIONS: Although most PCPs indicate familiarity with IC/PBS, they manage the condition infrequently. They also appear to have significant knowledge deficits about the clinical characteristics of IC/PBS, and they indicate variable practice patterns in the diagnosis and treatment of the condition. Educational efforts directed at PCPs will likely improve the care of patients with IC/PBS. PMID- 20303576 TI - Surgical reconstruction of the male urethral diverticulum. AB - OBJECTIVES: To describe the outcomes and reconstructive techniques used for men with symptomatic urethral diverticula in an attempt to standardize treatment based on the length of the urethral defect after diverticulum excision and the type of repair used. Urethral diverticula are rare in men and may be either congenital or acquired. METHODS: Between 2003 and 2008, 13 men were treated surgically for symptomatic urethral diverticula at a single institution by a single surgeon (C.M.G.). A total of 6 (46.2%) patients had urethral defects of < 4 cm and underwent excision of the diverticulum with primary anastomosis. Substitution urethroplasty using either penile skin or buccal mucosa was used in 7 (53.8%) patients with urethral defects of >or= 4 cm. Demographic and preoperative characteristics were compared among patients according to the length of the urethral defect. RESULTS: The mean age of men at the time of surgery was 38.4 years (+/- 13.0; range, 20.4-63.7), with a median follow-up time of 21.7 (+/ 29.0; range, 0.9-84.0) months. Neither age at the time of surgery, length of follow-up, or diverticulum volume was significantly different between men who underwent primary repair vs substitution urethroplasty. The overall success rate was 92% (12/13) with an overall complication rate of 42% at intermediate follow up. CONCLUSIONS: Outcomes after excision and primary anastomosis for diverticula associated with defects of < 4 cm were similar to outcomes after diverticulum excision and substitution urethroplasty for defect of >or= 4 cm. PMID- 20303577 TI - The role of uroflowmetry biofeedback and biofeedback training of the pelvic floor muscles in the treatment of recurrent urinary tract infections in women with dysfunctional voiding: a randomized controlled prospective study. AB - OBJECTIVES: To evaluate the efficacy of a training program with uroflowmetry biofeedback and pelvic floor relaxation biofeedback on urodynamic and voiding parameters in women with dysfunctional voiding. METHODS: Eighty-six women with recurrent urinary tract infections (UTIs) and dysfunctional voiding were randomly assigned to receive a treatment schedule as follows: uroflowmetry biofeedback (group 1), biofeedback training of the pelvic floor muscles (group 2), uroflowmetry biofeedback combined to biofeedback training of the pelvic floor muscles (group 3), no treatment (group 4). Patients were regularly evaluated by American Urological Association Symptom Index and urodynamics during the study period. All the patients were followed up for 1 year with monthly urine cultures. A further evaluation was done at month 24 by American Urological Association Symptom Index and free uroflowmetry with measurement of residual urine. RESULTS: The prevalence of storage and emptying symptoms decreased significantly at 3, 6, and 12 months in the groups 1, 2, and 3, and remained stable during the study period. Mean flow rate, flow time, voiding volume increased significantly, whereas postvoid residual urine decreased. The prevalence of UTI decreased significantly in groups 1, 2, and 3. At month 24, storage and emptying symptoms and voiding patterns were similar to the baseline values in all the patients. The incidence of UTIs was similar to baseline values in groups 1, 2, and 3. CONCLUSIONS: Training the voluntary control of the pelvic floor seems essential in obtaining control over the bladder function. These results reinforce the importance of pelvic floor therapy in the resolution of UTIs. PMID- 20303578 TI - Sentence context affects the brain response to masked words. AB - Historically, language researchers have assumed that lexical, or word-level processing is fast and automatic, while slower, more controlled post-lexical processes are sensitive to contextual information from higher levels of linguistic analysis. Here we demonstrate the impact of sentence context on the processing of words not available for conscious report by recording ERPs as sentences ended congruously or incongruously. Sentence final words were either masked to prevent their conscious identification, or were unmasked. For both masked and unmasked words, congruous completions elicited less negative ERPs than incongruous ones between 300 and 500ms after word onset (N400). Relative to the unmasked words, congruity effects in masked words were much smaller, began slightly later, and displayed a more anterior distribution. Results suggest contextual priming effects indexed by the N400 component reflect both automatic and controlled processes. Data are interpreted as suggesting a link between the neural generators of the N400 and conceptual short-term memory, a dynamic process for conceptual activation and structuring that is triggered by perceptual input. PMID- 20303579 TI - A review of heat transfer in human tooth--experimental characterization and mathematical modeling. AB - With rapid advances in modern dentistry, high-energy output instruments (e.g., dental lasers and light polymerizing units) are increasingly employed in dental surgery for applications such as laser assisted tooth ablation, bleaching, hypersensitivity treatment and polymerization of dental restorative materials. Extreme high temperature occurs within the tooth during these treatments, which may induce tooth thermal pain (TTP) sensation. Despite the wide application of these dental treatments, the underlying mechanisms are far from clear. Therefore, there is an urgent need to better understand heat transfer (HT) process in tooth, thermally induced damage of tooth, and the corresponding TTP. This will enhance the design and optimization of clinical treatment strategies. This paper presents the state-of-the-art of the current understanding on HT in tooth, with both experimental study and mathematical modeling reviewed. Limitations of the current experimental and mathematical methodologies are discussed and potential solutions are suggested. Interpretation of TTP in terms of thermally stimulated dentinal fluid flow is also discussed. PMID- 20303580 TI - Internet use and video gaming predict problem behavior in early adolescence. AB - In early adolescence, the time spent using the Internet and video games is higher than in any other present-day age group. Due to age-inappropriate web and gaming content, the impact of new media use on teenagers is a matter of public and scientific concern. Based on current theories on inappropriate media use, a study was conducted that comprised 205 adolescents aged 10-14 years (Md = 13). Individuals were identified who showed clinically relevant problem behavior according to the problem scales of the Youth Self Report (YSR). Online gaming, communicational Internet use, and playing first-person shooters were predictive of externalizing behavior problems (aggression, delinquency). Playing online role playing games was predictive of internalizing problem behavior (including withdrawal and anxiety). Parent-child communication about Internet activities was negatively related to problem behavior. PMID- 20303581 TI - Brief report: behaviorally induced insufficient sleep syndrome in older adolescents: prevalence and correlates. AB - The aim of the present study was to investigate the prevalence of "behaviorally induced insufficient sleep syndrome (BIISS)" which is a newly defined hypersomnia, among adolescents. BIISS is characterized by excessive daytime sleepiness, short habitual sleep duration and sleeping considerably longer than usual during weekend/vacations. The study was conducted in the Hordaland County, Norway using a cluster sampling procedure. In all, 1285 high school students (aged 16-19 years) participated by completing self-report questionnaires on a computer. The estimated prevalence of BIISS was 10.4%. The results from logistic regression analyses showed that use of alcohol and living in an urban area were positively related to BIISS, whereas a high level of education in mothers was negatively related to BIISS. BIISS was associated with poor grades and symptoms of anxiety and depression. PMID- 20303582 TI - Hydroxyapatite nucleation and growth mechanism on electrospun fibers functionalized with different chemical groups and their combinations. AB - Controlled nucleation and growth of hydroxyapatite (HA) crystals on electrospun fibers should play important roles in fabrication of composite scaffolds for bone tissue engineering, but no attempt has been made to clarify the effects of chemical group densities and the cooperation of two and more groups on the biomineralization process. The aim of the current study was to investigate into HA nucleation and growth on electrospun poly(dl-lactide) fibers functionalized with carboxyl, hydroxyl and amino groups and their combinations. Electrospun fibers with higher densities of carboxyl groups, combination of hydroxyl and carboxyl groups with the ratio of 3/7, and combination of amino, hydroxyl and carboxyl groups with the ratio of 2/3/5 were favorable for HA nucleation and growth, resulting in higher content and lower crystal size of formed HA. Carboxyl groups were initially combined with calcium ions through electrostatic attraction, and the introduction of hydroxyl groups could modulate the distance between carboxyl groups. The introduction of amino groups may lead to the inner ionic bonding with carboxyl groups, but can accelerate phosphate ions to form HA through a chelate ring with the calcium ion and carbonyl oxygen. The biological evaluation indicated that the mineralized scaffolds acted as an excellent cell support to maintain desirable cell-substrate interactions, to provide favorable conditions for cell proliferation and to stimulate the osteogenic differentiation. PMID- 20303583 TI - The effect of a laminin-5-derived peptide coated onto chitin microfibers on re epithelialization in early-stage wound healing. AB - Considerable effort has been directed towards regenerating defective tissues using tissue-engineering methods. Recently, peptides have been recognized as a valuable scientific tool in the field of tissue-engineering. The PPFLMLLKGSTR motif of the human laminin-5 alpha3 chain has been previously reported to promote keratinocyte survival; however, the in vivo effects of the PPFLMLLKGSTR motif have not yet been studied. These studies raised the hypothesis that a laminin-5 derived peptide can promote wound healing by accelerating re-epithelialization in vivo. To examine this hypothesis, we applied chitin microfibrous matrices coated with the PPFLMLLKGSTR motif in both rat and rabbit full-thickness cutaneous wound models. Compared with vehicle-treated and peptide-treated cutaneous wounds, the application significantly promoted early-stage wound healing by accelerating re epithelialization, notably reduced inflammatory cell infiltration, and prominently enhanced fibroblast proliferation. These findings support our hypothesis that the PPFLMLLKGSTR motif acts as a very effective wound healing accelerator by enhancing re-epithelialization. PMID- 20303584 TI - The synergistic effects of 3-D porous silk fibroin matrix scaffold properties and hydrodynamic environment in cartilage tissue regeneration. AB - Autologous cell-based tissue engineering using three-dimensional porous scaffolds has provided a good option for the repair of cartilage defects. Silk fibroin based scaffolds are naturally degradable materials with excellent biocompatibility and robust mechanical properties, indicating potential applications in cartilage tissue engineering. In this study, silk fibroin scaffolds prepared by freeze-drying (FD) and salt-leaching (SL300 and SL500) were fully characterized and used to study the effects of silk fibroin scaffold properties on chondrocyte attachment, proliferation and differentiation. The synergistic effects of scaffold properties and hydrodynamic environment generated by in vitro rocking culture were also investigated using static cultures as control. FD scaffolds with small pore size and lower porosity increased cell attachment but inhibited cell penetration and limited cell proliferation and differentiation. In contrast, SL scaffolds displaying a bigger pore size, higher porosity and crystallinity resulted in homogenous cell distribution, increasing cell proliferation and advanced chondrocyte differentiation in terms of their spherical morphology, predominant chondrogenic gene expression and abundant cartilaginous extracellular matrix production. A hydrodynamic environment was beneficial to chondrocyte proliferation, differentiation, and integrin gene expression in a pore size dependent manner with superior cartilage matrix production but limited hypertrophic differentiation obtained using chondrocyte seeded SL500 scaffolds. Integrin alpha5beta1 might mediate these effects. Chondrocyte/SL500 silk fibroin constructs obtained under in vitro rocking culture might serve as an excellent implant for in vivo cartilage defect reparation. PMID- 20303585 TI - Injectable PLGA based colloidal gels for zero-order dexamethasone release in cranial defects. AB - Bone fillers have emerged as an alternative to the invasive surgery often required to repair skeletal defects. Achieving controlled release from these materials is desired for accelerating healing. Here, oppositely-charged Poly (D,L lactic-co-glycolic acid) (PLGA) nanoparticles were used to create a cohesive colloidal gel as an injectable drug-loaded filler to promote healing in bone defects. The colloid self-assembled through electrostatic forces resulting in a stable 3-D network that may be extruded or molded to the desired shape. The colloidal gel demonstrated shear-thinning behavior due to the disruption of interparticle interactions as the applied shear force was increased. Once the external force was removed, the cohesive property of the colloidal gel was recovered. Similar reversibility and shear-thinning behavior were also observed in colloidal gels loaded with dexamethasone. Near zero-order dexamethasone release was observed over two months when the drug was encapsulated in PLGA nanoparticles and simply blending the drug with the colloidal gel showed similar kinetics for one month. Surgical placement was facilitated by the pseudoplastic material properties and in vivo observations demonstrated that the PLGA colloidal gels stimulated osteoconductive bone formation in rat cranial bone defects. PMID- 20303586 TI - Mesenchymal stem cell seeded knitted silk sling for the treatment of stress urinary incontinence. AB - Stress urinary incontinence remains a worldwide problem affecting patients of all ages. Implantation of suburethral sling is the cornerstone treatment. Current slings have inherent disadvantages. This study aims to develop a tissue engineered sling with bone marrow derived mesenchymal stem cell seeded degradable silk scaffold. The mesenchymal stem cells were obtained from Sprague-Dawley rats and were characterized in vitro. Layered cell sheets were formed after two weeks of culture and were labeled with carboxyfluorescein diacetate. Forty female rats were divided into four groups: Group A (n=5) had sham operation; other three groups underwent bilateral proximal sciatic nerve transection and were confirmed with stress urinary incontinence by the leak-point pressure measurement at 4 weeks after operation. Then, Group B (n=5) had no sling placed; Group C (n=15) was treated with a silk sling; and Group D (n=15) was treated with the tissue engineered sling. Histology and the leak-point pressure measurements were done at 4 and 12 weeks after the sling implantation while collagen content and mechanical testing were done at 12 weeks. The results showed that Group B had a significantly lower leak-point pressure (24.0+/-4.2 cmH(2)O) at 4 weeks (P<0.05), while Group C (38.0+/-3.3 cmH(2)O) and Group D (36.3+/-3.1 cmH(2)O) almost reached to the normal level shown by Group A (41.6+/-3.8 cmH(2)O) (p>0.05). At 12 weeks, tissue engineered sling of group D has higher collagen content (70.84+/ 14.49 microg/mg) and failure force (2.436+/-0.192 N) when compared those of Group C (38.94+/-7.05 microg/mg and 1.521+/-0.087 N) (p<0.05). Both the silk sling and tissue engineered sling showed convincing functional effects for the treatment of stress urinary incontinence in a rat model. And the better ligament-like tissue formation in the tissue engineered sling suggested potential long-term function. PMID- 20303587 TI - Differential expression and distribution of placental glutathione peroxidases 1, 3 and 4 in normal and preeclamptic pregnancy. AB - Preeclampsia is a pregnancy-specific condition affecting 2-7% of women and a leading cause of perinatal and maternal morbidity and mortality; it may also predispose the mother and fetus to increased risks of adult cardiovascular disease. The selenoprotein glutathione peroxidases (GPxs) have critical roles in regulating antioxidant status. OBJECTIVES, STUDY DESIGN AND MAIN OUTCOME MEASURES: Immunohistochemical measurements of GPx1, GPx3 and GPx4 protein expression were performed on samples taken from three standardised sampling sites between the cord insertion and the periphery of the placenta from 12 normotensive, and 12 preeclamptic women to establish if their expression differed between sampling sites. Total GPx activities were also examined from the three sampling sites of these placentae. RESULTS: There were highly significant reductions in overall immunohistochemical staining of all 3 GPxs in the preeclampsia compared to normotensive placentae (GPx1: P=0.016; GPx3: P=0.003; GPx4: P<0.001). Furthermore, graded differences in expression between the standardised placental sampling sites were also found for GPx3 (higher in the inner region, P=0.05) and GPx4 (higher in the periphery, P=0.02) but not GPx1. Placental GPx enzyme activity was also significantly reduced in tissue from preeclamptic women as compared to normotensive women (P=0.007; the difference was more pronounced nearest the cord insertion). CONCLUSIONS: We have shown highly significant reductions in expression of all three major classes of GPx in placentae from women with preeclampsia, and distribution gradients in activity, which may relate to the differential oxygenation of regions of the placenta. PMID- 20303588 TI - Placental characteristics of selective birth weight discordance in diamniotic monochorionic twin gestations. AB - Up to 21% of diamniotic-monochorionic twin pregnancies are complicated by severe birth weight discordance in the absence of twin-to-twin transfusion syndrome, a serious condition termed 'selective' birth weight discordance. While its pathogenesis remains incompletely understood, the development of selective intertwin growth discordance, related to fetal growth restriction of one twin, is generally attributed to aberrant placental characteristics. The aim of this study was to characterize the placental markers of selective birth weight discordance, with special emphasis on the choriovascular architecture. A prospective cohort of 319 consecutive diamniotic/monochorionic twin placentas was examined at Women and Infants Hospital between 2001 and 2009. After exclusion of placentas from pregnancies complicated by twin-to-twin transfusion syndrome (TTTS), monoamniotic, multiple and disrupted placentas, 216 placentas (36 birth weight (BW)-discordant and 180 BW-concordant) formed the subject of this study. Following dye injection, the anatomic characteristics and choriovascular anastomotic patterns of BW-discordant and BW-concordant placentas were compared. The BW-discordant placentas showed significantly higher frequencies of velamentous cord insertion (22% versus 8%, P < 0.001) and uneven placental sharing (56% versus 19%, P < 0.0001) compared with BW-concordant placentas. The frequencies of intertwin AA, VV and AV anastomoses, the net number of AV anastomoses, and the net cross-sectional area of AV anastomoses were similar in both groups. There was no correlation between the frequency of velamentous cord insertion and degree of placental sharing or patterns of choriovascular anastomoses in either group. In conclusion, velamentous cord insertion and uneven placental sharing are the two major placental determinants of selective birth weight discordance in diamniotic-monochorionic twins. The role of the intertwin anastomoses, even when unbalanced, is likely negligible. Elucidation of the mechanisms whereby velamentous cord insertion affects fetal growth may lead to more focused and effective therapeutic strategies for twin and singleton pregnancies complicated by dysregulated fetal growth. PMID- 20303590 TI - Prognostic classification of patients with acute lymphoblastic leukemia by using gene copy number profiles identified from array-based comparative genomic hybridization data. AB - The development of risk-adapted therapy has improved the treatment results of acute lymphoblastic leukemia (ALL) especially in children. However, more accurate risk classifiers are warranted. In this study we aimed at defining a prognostic classifier based on DNA copy number alterations of adolescent and young adult (AYA) (10-25 yrs) ALL patients (n=60) determined by microarray CGH and the relapse status of the patients. As a result of prognostic model identification procedure, we got a model of four genes: BAK1, CDKN2C, GSTM1, and MT1F, the copy number profile combinations of which differentiated AYA ALL patients at diagnosis depending on their risk of relapse. The performance of the model was poorer on other age groups. We suggest that this kind of approach produces models simple and accurate enough for potential use in ALL routine classification. PMID- 20303589 TI - Effect of genetic deletion of the vanilloid receptor TRPV1 on the expression of Substance P in sensory neurons of mice with adjuvant-induced arthritis. AB - The neuropeptide Substance P (SP), expressed by nociceptive sensory afferents in joints, plays an important role in the pathogenesis of arthritis. Capsaicin causes neurons in the dorsal root ganglia (DRG) to release SP from their central and peripheral axons, suggesting a functional link between SP and the capsaicin receptor, the transient receptor potential vanilloid 1 (TRPV1). The expression of both TRPV1 and SP have been reported to increase in several models of arthritis but the specific involvement of TRPV1-expressing articular afferents that can release SP is not completely understood. We here wanted to ascertain whether the increase in the number of SP-positive primary afferents in arthritis may be affected by genetic deletion of TRPV1. For this, we used immunohistochemistry to quantify the expression of SP in primary afferent neurons in wild-type mice (WT) vs. TRPV1-knockout (KO) mice with adjuvant-induced arthritis (AIA). We found that the expression of SP in DRG (1) increased significantly over naive level in both WT and KO mice 3 weeks after AIA, (2) was significantly higher in KO mice than in WT mice in naive mice and 2-3 weeks after AIA, (3) was significantly higher on the side of AIA than on the contralateral, vehicle-injected side at all time points in WT mice, but not in KO mice, and (4) increased predominantly in small size neurons in KO mice and in small- and medium-size neurons in WT mice. Since the size distribution of SP-positive DRG neurons in arthritic TRPV1-KO mice was not significantly different from that in naive mice, we speculate that the increased expression of SP is unlikely to reflect recruitment of A-fiber primary afferents and that the higher expression of SP in KO mice may represent a plastic change to compensate for the missing receptor in a major sensory circuit. PMID- 20303591 TI - Results of a multifaceted Intimate Partner Violence training program for pediatric residents. AB - OBJECTIVE: To evaluate the efficacy of a multifaceted Intimate Partner Violence (IPV) intervention on knowledge, attitudes, and screening practices of pediatric residents. METHODS: The intervention included: an on-site IPV counselor, IPV training for attending physicians, residents and social workers, and screening prompts. Evaluation included baseline and post-training surveys of residents, assessing their knowledge, attitudes, and comfort with IPV screening, patient chart reviews at baseline, 3 months, and 8 months for documentation of IPV screening, and review of the IPV counselor's client charts. RESULTS: Baseline chart review showed screening rates of less than 1%. Screening rates were 36.2% at 3 months and 33.1% at 8 months. After training, residents were more likely to know: IPV screening questions (47.1% vs. 100%); referral sources (34.3% vs. 82.9%); and the relationship between child abuse and IPV (52.9% vs. 97.1%). At baseline, barriers to IPV screening included time (50%), lack of knowledge of how to screen (26.5%) and where to refer (23.5%). Post-training, barriers were time (44%), presence of children (25.9%) or other adults (18.5%) in the room, and inappropriate location (18.5%). Post-training, none of the residents listed "lack of knowledge" or "lack of referral sources" as barriers to IPV screening. After 12 months, 107 victims of IPV were identified; most referred from inpatient units and subspecialty clinics. CONCLUSION: A multifaceted IPV intervention increased identification of IPV victims and markedly improved attitudes, comfort, and IPV screening practices of pediatric residents. IPV screening rates were sustainable with minimal ongoing training. PRACTICE IMPLICATIONS: Consideration should be given to the training and practice supports necessary to encourage IPV screening in the pediatric setting. Educational efforts that familiarize pediatricians with the content surrounding the risk and potential impact of IPV to children and families along with practice supports that make incorporating screening for IPV as easy as possible have the potential to increase the identification of this problem and promote referrals to IPV agencies for follow-up and intervention where needed. PMID- 20303592 TI - Stabilizing group treatment for Complex Posttraumatic Stress Disorder related to childhood abuse based on psycho-education and cognitive behavioral therapy: a pilot study. AB - OBJECTIVE: This study tests a Stabilizing Group Treatment protocol, designed for the management of the long-term sequelae of child abuse, that is, Complex Posttraumatic Stress Disorder (Complex PTSD). Evidence-based treatment for this subgroup of PTSD patients is largely lacking. This stabilizing treatment aims at improving Complex PTSD using psycho-education and cognitive behavioral interventions. METHOD: Thirty-six patients with a history of childhood abuse, Complex PTSD and severe co-morbidity entered a 20-week treatment with pre-, post , and follow-up-assessments. RESULTS: Improvement was found for PTSD and borderline symptoms. Post-treatment 64% and after 6 months 78% of patients no longer met criteria for Complex PTSD. CONCLUSIONS: This open study indicates both the feasibility of investigating treatment outcome and the initial efficacy of stabilizing group treatment in severely ill patients with Complex PTSD related to childhood abuse. PMID- 20303593 TI - Metal embryotoxicity from urban particles in Sao Paulo city: an experimental study in chicken embryos. AB - Chicken eggs were inoculated with suspensions of ambient air particles (16 for two consecutive weeks and meeting DSM-IV criteria for major depressive disorder. RESULTS: The cumulative probability of remission onset was 0.62 (SE=0.05) and 0.80 (SE=0.05) at 3 and 6 months following study entry. The relapse risk was 0.28 (SE=0.05) at 6 months post remission onset; 53% of those relapsing did so in the first 2 months post remission onset. Predictors of longer times to remission onset included: longer illness length, higher anxiety scores and unemployment; higher anxiety scores predicted relapse. The course pattern is similar to that reported previously. LIMITATIONS: These findings apply to inpatients only. Course was not rated blind to all of the participants' baseline data. CONCLUSIONS: Defining remission onset and relapse using this model is associated with a replicable course pattern. A singular clinical advantage of the model is the identification of those participants at highest risk of relapse 2 months post remission onset. PMID- 20303601 TI - Influence of age on the efficacy of electroconvulsive therapy in major depression: a retrospective study. AB - BACKGROUND: Several variables have been studied as possible predictors for the efficacy of ECT, results from the few studies assessing the influence of age on the efficacy of ECT were inconsistent. In older patients suffering from severe depression, ECT is often the treatment of choice, therefore, investigating the influence of age on ECT response is considered relevant. METHOD: At two depression units, 141 patients meeting DSM-IV criteria for major depression and scores of at least 18 on the 17-item Hamilton Rating Scale for Depression (HAM-D) were treated with bilateral ECT, twice weekly. Clinical evaluation of depressive symptoms was performed each week; scores on the HAM-D were obtained 1-3 days prior to ECT and 1-3 days after termination of the ECT course. The primary outcome criterion was defined a priori as the mean change on the HAM-D score. The influence of age on mean change on the HAM-D score was analyzed with multiple linear regression analysis, adjusted for three covariables: center, duration of the index episode and presence of psychotic features. RESULTS: Age as a continuous variable had no significant effect on the efficacy of ECT as measured by mean change on the HAM-D score (SE 0.057, p=0.84). LIMITATIONS: The disproportionate distribution of patients among the three age groups appears to be the major limitation of the present study. CONCLUSION: This study suggests that the efficacy of ECT in elderly depressed patients is at least equal to that in younger depressed patients. PMID- 20303602 TI - CD40 is a regulator for vascular endothelial growth factor in the tumor microenvironment of glioma. AB - CD40 is expressed in many tumor cells, however, its role in tumor biology is yet to be demonstrated. In the present study, we investigated the role of CD40 in gliomas. In vivo, we evaluated CD40 expression in 95 glioma tissues and 10 non tumorous brain tissues and investigated the relationship between histopathological parameters, vascular density, and vascular endothelial growth factor (VEGF) expressions. In vitro, we aimed to understand the biological relevance of CD40 and VEGF in glioma cell lines. The results clearly demonstrated that CD40 expression, including membranous and cytoplasmic staining, was significantly higher in poorly differentiated and well differentiated gliomas than in the non-tumorous brain tissues (P=0.045 and P=0.043, respectively). In gliomas, the expression of CD40 was significantly correlated with tumor size, VEGF expressions and microvessel density (MVD) (P=0.022, P=0.023 and P=0.0316, respectively). In the in vitro study, stimulation of human glioma cells by CD40 ligation induced the expression and secretion of VEGF and was blocked by anti CD40 monoclonal antibody. These observations provide evidence that CD40 ligation supports the expression and secretion of VEGF and may be involved in neovascularization of gliomas, they also suggest that CD40 and VEGF may be useful biomarkers for evaluating the risk of developing gliomas, and may also be used as a target for therapy. PMID- 20303603 TI - Endoscopic treatment of pharyngo-esophageal diverticulum in child. AB - Pharyngo-esophageal diverticula are extremely rare among children. Treatment in adults usually consists of endoscopic resection of the crico-pharyngeal muscle but application of this surgical procedure in children has not been reported before. We report the case of a 5-year-old boy whose recurrent pulmonary infection and chronic low weight led to diagnosis of a pharyngeal diverticulum. The diverticulum was removed by endoscopic CO(2) laser surgery. No relapse occurred during the 4-year follow-up period after surgery. PMID- 20303605 TI - The impact of novel exercise criteria and indices for the diagnostic and prognostic ability of exercise testing. AB - Exercise testing (ET) stands as one of the most easy, affordable, cost effective, non invasive methods for diagnosing coronary heart disease. Its sensitivity, specificity and prognostic value, especially in the prime era of its implementation in the cardiac diagnostic procedure, is relatively limited. Novel exercise criteria and indices based either on ST segment changes or ST segment independent parameters, such as "Athens QRS score", have greatly improved the diagnostic ability and accuracy of ET. Complex ECG-derived indices linked to ST changes along with the use of right-sided precordial leads have also enhanced the diagnostic accuracy of ET with respect to the extent of ischemic heart disease and the detection of specific culprit vessels. ET contains also a prognostic value, since several ET-derived parameters have been associated with adverse outcome, including ST changes, blood pressure and heart rate response to exercise and duration of exercise. PMID- 20303604 TI - The universal newborn hearing screening in Brazil: from identification to intervention. AB - OBJECTIVE: The objective of the study is to investigate the results of the newborn hearing screening program carried out in a Public Hospital in Brazil, in the first 3 years regarding: (1) the prevalence of hearing impairment; (2) the influence of the universal hearing screening program on the age at which the diagnosis of hearing loss is defined; (3) the cost effectiveness of the program; (4) the outcomes, in terms of the age in which the hearing rehabilitation started. METHODS: A descriptive study of the first 3 years after starting the universal newborn hearing screening in a Public Hospital of Bauru, Sao Paulo state, Brazil. The screening method consists of a two-stage screening approach with transient otoacoustic emissions (TOAE), conducted by an audiologist. If the outcome in the second-stage screening is REFER, the infant is submitted to diagnostic follow-up testing and intervention at the Audiology and Speech Pathology Clinic at the University of Sao Paulo, campus of Bauru. The evaluation of the costs of the universal newborn hearing screening program per each screened newborn (around 4000/year) was done based on a proposal by the National Center for Hearing Assessment and Management, of the Utah State University, United States of America. RESULTS: 11,466 newborns were submitted to hearing screening, corresponding to 90.52% of the living newborns. The prevalence of sensorineural hearing loss was 0.96:1000. Of the 11 children with sensorineural hearing loss, eight children received hearing aids and five started the therapeutic process before the age of 1. Currently, four children between the ages of 11 months and 2 years old were submitted to cochlear implant surgery. The cost of hearing screening was US$7.00 and the annual cost of the universal newborn hearing screening program was US$26,940.47. CONCLUSION: The hospital-based universal newborn hearing screening carried out through the Brazilian National Health System is viable, with promising results. However, in a country such as Brazil, which presents large socio-economic differences, the same type of analyses should be performed in several regions, so as to take into account specific aspects, to implement the newborn hearing screening along with the Public System. PMID- 20303606 TI - Low energy biphasic cardioversion of atrial flutter: results from a pilot trial. AB - A pilot study was performed to determine the efficacy of low energy biphasic external cardioversion in common type atrial flutter. In the majority of patients (70%) successful cardioversion was achieved with low energy levels of 20 or 30 J; however a considerable number of patients (15%) were initially cardioverted to atrial fibrillation, needing an additional cardioversion with an even higher energy level. PMID- 20303607 TI - Increased serum neopterin in patients with nonrheumatic aortic valve stenosis. AB - BACKGROUND: Inflammation and immunity play an intrinsic role in the pathogenesis of NR-AS. Neopterin is mainly produced by activated macrophages. METHODS: We examined serum neopterin levels in 51 patients undergoing valve replacement surgery [37 NR-AS and 14 aortic regurgitation (AR)]. RESULTS: Serum neopterin levels were significantly higher in patients with NR-AS than in those with AR and age matched controls, whereas serum high-sensitivity C-reactive protein (hs-CRP) levels did not differ among three groups. Moreover, serum neopterin levels were not different between NR-AS patients with and without coronary artery disease. CONCLUSIONS: Serum neopterin levels appear to be a useful maker in patients with NR-AS. PMID- 20303608 TI - Development of stress resistance in Staphylococcus aureus after exposure to sublethal environmental conditions. AB - The ability of Staphylococcus aureus to develop stress resistance responses was investigated. Exponential growth phase cells of S. aureus CECT 4459 were exposed to sublethal conditions (acid and alkaline pH, hydrogen peroxide, and heat) and then the acquisition of resistance to acid (pH 2.5), alkali (pH 12.0), hydrogen peroxide (50mM), and heat (58 degrees C) was determined. Conditions resulting in the maximum development of homologous resistance (tolerance to the same stress), while preventing lethal effects in the population, were pH 4.5 (2h), pH 9.5 (30 min), 0.05 mM H(2)O(2) (30 min), and 45 degrees C (2h). Under these adaptation conditions, times for the first decimal reduction (TFDC) to a lethal treatment at acid pH, alkaline pH, hydrogen peroxide, and heat were increased by a factor of 1.6, 2, 2, and 6, respectively. The presence of chloramphenicol or rifampicin in the adaptation medium completely abolished the increase in homologous resistance to acid pH and to hydrogen peroxide. By contrast, the development of homologous resistance to alkaline pH resulted independently of the presence of either chloramphenicol or rifampicin. S. aureus heat resistance increased in the presence of the inhibitors during the heat shock, but only partially. In some cases, the exposure to a given stress induced cross-protection against other agents. Protective combinations of sublethal stress and lethal agents were: acid pH-heat, acid pH-hydrogen peroxide, alkaline pH-hydrogen peroxide, heat-acid pH, and heat-hydrogen peroxide. These combinations of agents applied sequentially should be avoided in food-processing environments. PMID- 20303609 TI - Carotenoid production in Lactobacillus plantarum. AB - Eighteen strains of Lactobacillus plantarum from different origins were screened for carotenoid production, as many of them exhibited a deep yellow pigmentation when cultured as isolated colonies on MRS-agar plates. We found that most of them produced significative amounts of the yellow C(30) carotenoid 4,4' diaponeurosporene in the range 1.8 to 54 mg/kg of dry cell weight. Although some of the strains produced just trace amounts of this carotenoid, PCR studies showed that all of them harbored the genes crtM and crtN which, inferred from homology, had been predicted in the three L. plantarum complete genome sequences currently available. Our results suggest the full functionality of a C(30) carotenoid biosynthesis pathway in this species, driven by the operon crtNM. DNA sequencing of the entire crtNM operon in the maximum carotenoid-producing strain found in this study, i.e. L. plantarum CECT7531, was accomplished. Genes crtM and crtN were annotated as dehydrosqualene synthase and dehydrosqualene desaturase, respectively, in this strain. PMID- 20303610 TI - Inhibition of multifunctional dipeptidyl peptidase-IV: is there a risk of oncological and immunological adverse effects? AB - Inhibitors of dipeptidyl peptidase-IV (DPP-IV) are a novel class of anti-diabetes drugs; inhibiting the breakdown of incretins, they increase their biological availability and decrease thus blood glucose levels. However, in addition to regulating glucose homeostasis, DPP-IV has many diverse functions, such as modulating cell growth, differentiation and transformation and immune function. Within the immune system, DPP-IV exerts mainly stimulating effects, while its relation to malignancies is highly variable. Therefore, long-term inhibition of this enzyme could have serious side effects including immune dysregulation or increased risk of cancer. Although the data on the effects of DPP-IV inhibitors in humans are scarce, the increased risk of infections and the tendency towards a higher incidence of some tumours fall in line with experimental evidence suggesting the possibility of their adverse immunological and oncological effects. Further research is obviously needed to clarify the effector mechanisms of DPP-IV inhibitors on immune function and tumour biology. Most important, however, is obtaining reassuring safety data from adequately powered, long-term trials of DPP-IV inhibitors in humans. In the meantime, all the potential risks of DPP-IV inhibitors should be kept in mind, and this class of drugs needs to be regarded with some degree of caution. PMID- 20303611 TI - Extracellular production of reactive oxygen species during seed germination and early seedling growth in Pisum sativum. AB - Extracellularly produced reactive oxygen species (ROS) play key roles in plant development, but their significance for seed germination and seedling establishment is poorly understood. Here we report on the characteristics of extracellular ROS production during seed germination and early seedling development in Pisum sativum. Extracellular superoxide (O2(.-)) and hydrogen peroxide (H2O2) production and the activity of extracellular peroxidases (ECPOX) were determined spectrophotometrically, and O2(.-) was identified by electron paramagnetic resonance. Cell wall fractionation of cotyledons, seed coats and radicles was used in conjunction with polyacrylamide gel electrophoresis to investigate substrate specificity and molecular masses of O2(.-)-producing enzymes, and the forces that bind them to the cell wall. Seed imbibition was accompanied by an immediate, transient burst of redox activity that involved O2(. ) and other substances capable of oxidizing epinephrine, and also H2O2. At the final stages of germination, coinciding with radicle elongation, a second increase in O2(.-) but not H2O2 production occurred and was correlated with an increase in extracellular ECPOX activity. Electrophoretic analyses of cell wall fractions demonstrated the presence of enzymes capable of O2(.-) production. The significance of extracellular ROS production during seed germination and early seedling development, and also during seed aging, is discussed. PMID- 20303612 TI - Discordance in the histopathologic diagnosis of melanoma at a melanoma referral center. AB - BACKGROUND: Histopathologic analysis remains the gold standard for the pathologic diagnosis of melanoma. Numerous histologic criteria are used to diagnose melanoma, but none alone are sufficient to establish this diagnosis. Therefore, differentiating between benign pigmented lesions and melanoma may be controversial. Although several studies have examined the interobserver variability in the pathological diagnosis of melanoma, the prevalence of discordant diagnoses of melanocytic neoplasms is unknown. OBJECTIVE: We sought to examine the discordance rate of melanoma diagnoses referred to our pigmented lesion clinic, a subset of the University of California, San Francisco (UCSF) Department of Dermatology and Comprehensive Cancer Center Melanoma Center during a 2-year period. METHODS: A total of 392 new patients given a diagnosis of thin melanoma (melanoma in situ, stage IA, stage IB) or benign nevus were referred in 2006 and 2007, with initial diagnoses rendered by an outside dermatopathologist or surgical pathologist. Subsequently, these specimens were re-evaluated by routine histopathologic examination at the UCSF Dermatopathology Service and a distinct diagnosis was rendered. The two available diagnoses were compared, and discordance was defined as the lack of agreement between two pathologists when rendering a benign versus malignant versus ambiguous diagnosis. RESULTS: The discordance rate of melanomas and nevi between the referring centers and UCSF was 14.3%. LIMITATIONS: This review was limited in that there were few patients with benign pigmented lesions referred to the pigmented lesion clinic at UCSF. CONCLUSION: The level of discordance in the routine histopathologic interpretation of melanocytic neoplasms can be high. PMID- 20303613 TI - New World cutaneous leishmaniasis: updated review of current and future diagnosis and treatment. AB - BACKGROUND: Cutaneous leishmaniasis (CL) has traditionally been underrecognized and underreported. Improved awareness is warranted as the number of cases has increased as a result of increased travel to endemic countries, the HIV/AIDS pandemic, and the larger number of military and contract workers deployed overseas. OBJECTIVE: We sought to present a systematic review of evidence from a gamut of research trials on the treatment efficacy of different regimens and aggregate this knowledge for use as a guide for clinical practice decisions. METHODS: We performed a comprehensive search of print and electronic sources to identify the accumulated research information on New World CL. RESULTS: Topical treatment of New World CL lesions is generally not recommended. Findings support the systemic administration of pentavalent antimonials as first-line treatment. Exception to this is infection with L guyanensis in French Guiana where systemic pentamidine is suggested as first-line treatment. LIMITATIONS: The reliability of the findings of this review of research evidence is dependent on the individual quality and potential bias in its component principal trials. There was a conscious attempt to only include evidence derived from randomized controlled studies, with adequate randomization, adequate patient numbers, and complete follow-up information. However, because of the relatively small number of such studies on New World CL, evidence from nonrandomized studies and case series studies was also considered. CONCLUSIONS: The pentavalent antimony compounds remain the first-line treatment choice for the treatment of New World CL. Concerns with cost, availability, poor compliance, and systemic toxicity, however, may compel clinicians to opt for alternative treatment modalities. Some advances in the development of an antileishmanial vaccine have been made but none is yet available for clinic use. The increase, over recent years, in the incidence of CL warrants an enhanced effort to increase awareness of the disease, assure timely diagnosis, and implement effective management and treatment strategies. PMID- 20303614 TI - Application of a fluorescent dual stain to assess decontamination of tissue protein and prion amyloid from surgical stainless steel during simulated washer disinfector cycles. AB - Current World Health Organization guidelines pertaining to the reprocessing of surgical instruments in the face of potential iatrogenic transmission of Creutzfeldt-Jakob disease (iCJD) are incompatible for the vast majority of devices. This has led to the advent of a range of new decontamination measures. Even without the implementation of these new procedures, the incidence of proven iCJD through surgery remains low. In this study, existing decontamination processes in sterile service departments have been evaluated using simulated washer-disinfector cycles on surgical grade stainless steel wires inoculated with ME7 scrapie homogenate. The consequence of varying the soil drying times and choice of cycle pre-treatment on prion removal were evaluated. Assessment of residual contamination at each cycle phase was carried out with the application of a sensitive fluorescent staining procedure to identify both total protein and prion-associated amyloid. The study confirmed that immediate reprocessing following contamination was beneficial during the pre-treatment phase with either an enzymatic or pre-soak wetting agent. Final total protein levels at the end of the cycles, were not significantly different from those where the soil was allowed to dry. In addition, cycles involving a pre-treatment with either an enzymatic cleaner or pre-soak, whether the soil was allowed to dry or not, showed complete removal of detectable prion amyloid. The results suggest that current decontamination procedures, combined with immediate processing of surgical instruments, have the potential to be highly effective alone at reducing the risk of surgical transmission of CJD. PMID- 20303615 TI - Patterns of resolution of infectious parameters in multidrug-resistant Acinetobacter baumannii ventilator-associated pneumonia. PMID- 20303616 TI - European Centre for Disease Prevention and Control swine flu guidelines: 'cough hygienically' into your sleeve? PMID- 20303617 TI - Emergence of an extreme-drug-resistant (XDR) Acinetobacter baumannii carrying blaOXA-23 in a patient with acute necrohaemorrhagic pancreatitis. PMID- 20303618 TI - Assessment of peripheral arterial catheters as a source of sepsis in the critically ill: a narrative review. AB - Intravascular devices (IVDs) are essential in the management of critically ill patients; however, IVD-related sepsis remains a major complication. Arterial catheters (ACs) are one of the most manipulated IVDs in critically ill patients. When bloodstream infection (BSI) is suspected in a patient with an IVD in situ, clinicians have focused their attention on the central venous catheter (CVC) while largely ignoring the AC. Although it would be routine for the CVC to be cultured and replaced if necessary for suspected IVD or catheter-related sepsis, the AC may not be treated in the same manner. The reasons for this may in part relate to the patient groups studied. In lower acuity patients with short dwell times, AC sepsis rates are indeed low. In the higher acuity patient, earlier studies suggested that ACs had an infective potential at least equal to short term CVCs, a finding that has translated poorly into clinical practice. It has been estimated that there may be up to 48,000 BSIs per year arising from ACs in the USA alone, suggesting a significant clinical problem. Recent evidence now shows that the infective potential of the AC is comparable with that in short term CVCs regarding both colonisation (which precedes BSI) and BSI, consolidating earlier studies. In critically ill patients suspected of catheter-related bloodsteam infection it is suggested that both the AC and CVC must now be assessed together. PMID- 20303619 TI - Working awareness of healthcare workers regarding sterilisation, disinfection, and transmission of bloodborne infections and device-related infections at a tertiary care referral centre in north India. PMID- 20303620 TI - Olfactory and gustatory hallucinations presenting as partial status epilepticus because of glioblastoma multiforme. AB - Olfactory and gustatory hallucinations are not often encountered in the acute care setting but may represent the subtle presenting features of a significant underlying disease process. We describe a patient whose most striking presenting symptoms were of olfactory and gustatory hallucinations and in whom the diagnosis and treatment of a new brain tumor and partial status epilepticus occurred entirely in the emergency department. The lesion was subsequently identified as glioblastoma multiforme involving the hippocampus and amygdala. PMID- 20303621 TI - Reducing error in the emergency department: a call for standardization of the sign-out process. PMID- 20303622 TI - [Barium aspiration pneumonitis in an elderly patient under investigation for progressive dysphagia]. PMID- 20303623 TI - [The dawn of a pandemic. Description of an influenza A outbreak seen in a Health Centre in Leganes (Madrid) during the months of May to July 2009]. PMID- 20303624 TI - [Urgent urinary incontinence due to taking troxerutine sachets]. PMID- 20303625 TI - Synthesis, X-ray structures and cytotoxic activity of platinum(II), palladium(II) and copper(II) complexes with chelating ligands. AB - Here we present the synthesis of the new chelating ligands 1-benzothiazol-2-yl-5 (2-hydroxyphenyl)-3-methyl-1H-pyrazole-4-carboxylic acid methyl ester (2a) and 1 (6-chloropyridazin-3-yl)-5-(2-hydroxyphenyl)-3-methyl-1H-pyrazole-4-carboxylic acid methyl ester (2b), obtained in the reaction of 2-methyl-4-oxo-4H-chromene-3 carboxylic acid methyl ester (1) with hydrazine derivatives. These ligands 2a and 2b create solid complexes with Pt(II) (4a, 4b), Pd(II) (5a, 5b) and Cu(II) (6a, 7a, 8a, 8b and 9b) metal ions or can be cyclized to 1-benzothiazol-2-yl-3-methyl 1H-chromeno[4,3-c]pyrazol-4-one (3a) or 1-(6-chloropyridazin-3-yl)-3-methyl-1H chromeno[4,3-c]pyrazol-4-one (3b). The crystal and molecular structures of ligand 2a, its Cu(II) complexes 6a and 7a were determined by X-ray diffraction method. Cytotoxic activity of the ligands 2a and 2b and their complexes 4a, 4b, 5a, 5a, 6a, 8a, 8b and 9b, and modulation of expression of BAX and P53 genes are also shown. PMID- 20303626 TI - Design and synthesis of 1,4-dihydropyridine derivatives as BACE-1 inhibitors. AB - BACE-1 has been shown to be an attractive therapeutic target in Alzheimer's disease (AD). Using a 1,4-dihydropyridine (DHP) scaffold, we synthesized new inhibitors of BACE-1 by modifying the known BACE inhibitor 2 containing a hydroxyethylamine (HEA) motif. Using structure-based drug design based on computer-aided molecular docking, the isophthalamide ring of 2 was replaced with a 1,4-dihydropyridine ring as a brain-targeting strategy. Several of the new dihydropyridine derivatives were synthesized and their BACE-1-inhibitory activities were evaluated using a cell-based, reporter gene assay system that measures the cleavage of alkaline phosphatase (AP)-APP fusion protein by BACE-1. Most of the 1,4-DHP analogs showed BACE-1-inhibitory activities with IC50 values in the range 8-30 microM, suggesting that the 1,4-DHP skeleton may be utilized to develop brain-targeting BACE-1 inhibitors. PMID- 20303627 TI - [Hypereosinophilic syndromes: pathogenic and therapeutic up-to-date]. AB - The hypereosinophilic syndromes (HES), defined by an unexplained and sustained hypereosinophilia, can be associated with heterogeneous hematological conditions. Several molecular mechanisms underlying the eosinophilia, which remained indeterminate for a long time, have been recently identified. These recent advances allowed a better classification of the various forms of HES and the development of targeted therapies. The role of tyrosine kinases, especially PDGFRA, and the efficacy of tyrosine kinases inhibitors dramatically improved the diagnosis and the treatment of myeloproliferative variant of HES. On the other side, eosinophilia can be driven by IL-5 secreting abnormal and often clonal T cell subsets (lymphocytic variant of HES). The crucial role of this cytokine in eosinophil development, activation and survival leads to the assessment of anti IL-5 monoclonal antibodies which have recently shown to provide a significant corticosteroid sparing effect in FIP1L1-PDGFRA negative HES patients. Despite these major advances, half of HES remains unexplained (idiopathic HES). Some FIPL1-PDGFRA negative patients respond to imatinib, suggesting the role of other tyrosine kinases (or other partners than FIP1L1 in a fusion gene implicating PDGFRA). Development of new biomarkers is needed to help physicians in the diagnosis, classification of HES and in the choice of a targeted therapy. PMID- 20303628 TI - Radon mapping by retrospective measurements - an approach based on CDs/DVDs. AB - This article points out the ability to map retrospective (222)Rn concentrations by home stored CDs/DVDs. The method employs the high radon absorption ability of the polycarbonate material of CDs and DVDs and their track-etch properties. The principle steps for the application of the method are addressed. The possibility for individual a posteriori calibration is studied, demonstrating that better than 10% accuracy in retrospective measurements is potentially achievable. Results from retrospective measurements in three different regions are shown, demonstrating the potential of the method for large-scale radon mapping. Comparison with independently evaluated retrospective (222)Rn concentrations in places with known radon history was made and very good correspondence was observed. The experience indicates that the method can be used for large scale retrospective radon mapping and its applications can be expanded towards mapping of radon concentrations in water and soil gas. PMID- 20303629 TI - Recent 137Cs deposition in sediments of Admiralty Bay, Antarctica. AB - Cesium-137, radium-226 and lead-210 profiles of a 25 cm sediment core give an indication of recent changes in land-ocean interactions at a polar coastal environment (Admiralty Bay, King George Island, Antarctica). The linear sedimentation accumulation rate at the study site calculated from the unsupported (210)Pb profile was 6.7 mm/year from 1965 to 2005. A 3.5-fold increase in (137)Cs concentrations was observed in the top layer of this sediment core. This sharp increase seems to indicate a recent redistribution of fallout radionuclides previously deposited on soil, vegetation and snow. These results imply enhanced land-ocean interactions at this site likely as a result of climate change. Because our results are based on a single core, additional investigations are needed to confirm our observations. PMID- 20303630 TI - Natural radionuclide concentrations in two phosphate ores of east Algeria. AB - Ore is considered as an important source of many elements such as the iron, phosphorus, and uranium. Concerning the natural radionuclides, their concentrations vary from an ore to other depending on the chemical composition of each site. In this work, two phosphate ores found in East of Algeria have been chosen to assess the activity concentration of natural radionuclides represented mainly by three natural radioactive series (238)U, (235)U and (232)Th, and the primordial radionuclide (40)K where they were determined using ultra-low background, high-resolution gamma-ray spectroscopy. The measured activity concentrations of radioactive series ranged from 6.2 +/- 0.4 to 733 +/- 33 Bq.kg( 1) for the (232)Th series, from 249 +/- 16 to 547 +/- 39 Bq.kg(-1) for the (238)U series, around 24.2 +/- 2.5 Bq.kg(-1) for the (235)U series, and from 1.4 +/- 0.2 to 6.7 +/- 0.7 Bq.kg(-1) for (40)K. To assess exposure to gamma radiation in the two ores, from specific activities of (232)Th, (40)K and (226)Ra, three indexes were determined: Radium equivalent (Ra(eq)), external and internal hazard indexes (H(ex) and H(in)), their values ranged from 831 +/- 8 to 1298 +/- 14 Bq.kg(-1) for Ra(eq), from 2.2 +/- 0.4 to 3.5 +/- 0.7 Bq.kg(-1) for H(ex), and from 4.2 +/- 0.7 to 4.5 +/- 0.7 Bq.kg(-1) for H(in). PMID- 20303632 TI - Lowering postdialysis plasma sodium (conductivity) to increase sodium removal in volume-expanded hemodialysis patients: a pilot study using a biofeedback software system. AB - BACKGROUND: Extracellular fluid expansion is common in hemodialysis patients. Aggressive fluid removal may lead to intradialytic complications. High dialysate sodium concentrations may lessen complications, but may increase extracellular volume. We hypothesized that decreasing plasma sodium concentration during dialysis will increase sodium removal and decrease extracellular volume. STUDY DESIGN: Pilot clinical trial. SETTING & PARTICIPANTS: 16 patients with end-stage kidney disease treated using thrice-weekly hemodialysis at a university teaching hospital hemodialysis unit. INTERVENTION: Stepwise decrease in postdialysis plasma sodium level (calculated as end-of-session plasma conductivity) over 4 phases effected by dialysate conductivity measurement cells and a biofeedback software system (Diacontrol; Hospal, www.hospal.it) that allowed alteration of dialysate inlet conductivity and calculation of plasma conductivity. OUTCOMES: Decrease in postdialysis plasma sodium (conductivity) levels, sodium removal, redistribution of body water, and effect of these on interdialytic weight gain and blood pressure. MEASUREMENTS: Plasma sodium and conductivity values (the latter measured in millisiemens per centimeter); ionic mass balance (sodium removal); bioelectrical impedance analysis measurements of body-water compartments and phase angle; interdialytic weight gain; and blood pressure. RESULTS: Plasma sodium concentrations at the end of dialysis were decreased from 137.8 (phase 1) to 135.6 mmol/L (phase 4) and end-of-session plasma conductivity values were decreased from 14.0 (phase 1) to 13.5 mS/cm (phase 4; all mean values). Ionic mass balance increased from 383 to 480 mmol. Extracellular water was significantly decreased, phase angle was increased, and blood pressure and interdialytic weight gain were decreased. Plasma sodium levels correlated significantly with plasma conductivity; thus, changes in postdialysis plasma sodium levels can be inferred from changes in end-of-session plasma conductivity values. LIMITATIONS: Small number of patients. No information for dietary sodium intake. CONCLUSION: To decrease extracellular volume, it may be necessary to add diffusive to convective sodium losses. PMID- 20303631 TI - Cementless fixation of radial head implants is affected by implant stem geometry: an in vitro study. AB - BACKGROUND: Metal radial head implants are widely used for the management of unreconstructible fractures. However, the effect of implant stem design on initial fixation and stability is unknown. This study determined the effects of radial head stem geometry on the initial stability of the uncemented implant. It was hypothesized that cortical contact and hence increased fixation would be achieved with an increased stem diameter, stem length and a tapered shape. METHODS: Eleven radii received five implants with differing stem geometries: short and long undersized, short and long optimally sized and short tapered. Inferiorly-directed compressive loads were applied successively to the anterior, posterior, medial and lateral edges of the implants. Maximum contralateral radial head "lift-off" was quantified by the distance between bone and implant surface markers. FINDINGS: The short and long undersized implants experienced greater micromotion with approximately 100 microm and 160 microm more lift-off respectively (P<0.02). The remaining optimally sized and tapered implants averaged 50 microm. There was greater motion for the undersized implants loaded at the lateral position (P0.005). INTERPRETATION: This study shows that filling the diameter of the medullary canal is more important than filling the length of the canal. The taper did not offer any additional advantages compared to the straight stem, suggesting that reaming of bone to accept the taper did not produce enhanced initial purchase. If rigid initial implant fixation is desired with an uncemented radial head implant, a canal-filling stem reduces initial implant micromotion to less than 50 microm which may enhance bone ingrowth. PMID- 20303633 TI - Acute kidney injury in critically ill patients infected with 2009 pandemic influenza A(H1N1): report from a Canadian Province. AB - BACKGROUND: 2009 pandemic influenza A(H1N1) has led to a global increase in severe respiratory illness. Little is known about kidney outcomes and dialytic requirements in critically ill patients infected with pandemic H1N1. STUDY DESIGN: Prospective observational study. SETTING & PARTICIPANTS: 50 patients with pandemic H1N1 admitted to any of 7 intensive care units in Manitoba, Canada, were prospectively followed. OUTCOME & MEASUREMENTS: Outcomes were kidney injury and kidney failure defined using RIFLE (risk, injury, failure, loss, end-stage disease) criteria or need for dialysis therapy. RESULTS: The pandemic H1N1 group was composed of 50 critically ill patients with pandemic H1N1 with severe respiratory syndrome (47 confirmed cases, 3 probable). Kidney injury, kidney failure, and need for dialysis occurred in 66.7%, 66%, and 11% of patients, respectively. Mortality was 16%. Kidney failure was associated with increased death (OR, 11.29; 95% CI, 1.29-98.9), whereas the need for dialysis was associated with an increase in length of stay (RR, 2.38; 95% CI, 2.13-25.75). LIMITATIONS: Small population studied from single Canadian province; thus, limited generalizability. CONCLUSIONS: In critically ill patients with pandemic H1N1, kidney injury, kidney failure, and the need for dialysis are common and associated with an increase in mortality and length of intensive care unit stay. PMID- 20303634 TI - Decreased kidney function and crystal deposition in the tubules after kidney transplant. AB - Adenine phosphoribosyltransferase (APRT) deficiency is an autosomal recessive purine enzyme defect that results in the inability to utilize adenine, which consequently is oxidized by xanthine dehydrogenase to 2,8-dihydroxyadenine (2,8 DHA), an extremely insoluble substance eventually leading to crystalluria, nephrolithiasis, and kidney injury. We describe a case of APRT deficiency not diagnosed until the evaluation of a poorly functioning kidney transplant in a 67 year-old white woman. After the transplant, there was delayed transplant function, urine specimens showed crystals with unusual appearance, and the transplant biopsy specimen showed intratubular obstruction by crystals identified as 2,8-DHA using infrared spectroscopy. APRT enzymatic activity was undetectable in red blood cell lysates, and analysis of the APRT gene showed 1 heterozygous sequence variant, a duplication of T at position 1832. The patient was treated with allopurinol, 300 mg/d, and transplant function progressively normalized. Because patients with undiagnosed APRT deficiency who undergo kidney transplant may risk losing the transplant because of an otherwise treatable disease, increased physician awareness may hasten the diagnosis and limit the morbidity associated with this disease. PMID- 20303635 TI - Predicting violence in romantic relationships during adolescence and emerging adulthood: a critical review of the mechanisms by which familial and peer influences operate. AB - For three decades, researchers have sought to gain a greater understanding of the developmental antecedents to later perpetration or victimization of violence in romantic relationships. Whereas the majority of early studies focused on family of-origin factors, attention in recent years has turned to additional ecologies such as peer relationships. This review highlights accomplishments of both family and peer studies that focus on violent romantic relationships in an effort to summarize the current state of knowledge. Attention is given to epidemiology and developmental family and peer factors, with special attention given to mechanisms that mediate and/or moderate the relation between family and peer factors and later participation in violent relationships. A critical approach is taken throughout the review in order to identify limitations of previous studies, and to highlight key findings. A case is made for viewing these developmental antecedents as a result of multiple developmental ecologies that is perhaps best summarized as a culture of violence. PMID- 20303636 TI - Is flanker-based inhibition related to age? Identifying specific influences of individual differences on neurocognitive variables. AB - Researchers frequently attempt to identify the specific neurocognitive processes that might be responsible for differences in performance associated with neurological status or other individual difference characteristics by administering two or more conditions of an experimental task to different groups of participants, and focusing on the group-by-condition interaction as the primary outcome of interest. Three limitations of this approach are discussed, and an alternative analytical method is proposed to overcome the limitations. The method is demonstrated in analyses of data from 10 cognitive tasks in two independent studies, including two flanker tasks which are often used to assess aspects of inhibition. PMID- 20303637 TI - [The Archivos archive, 2009]. PMID- 20303638 TI - [Permissive and non-permissive hypercapnia: mechanisms of action and consequences of high carbon dioxide levels]. AB - Acute lung injury is a disease with high incidence of mortality and its treatment is still controversial. Increasing the levels of CO2 beyond the physiological range has been proposed as a potential protective strategy for patients on mechanical ventilation, as it could moderate the inflammatory response. In this article we review the published evidence on the role of CO2 during acute lung injury. We conclude that although there are reports suggesting benefits from hypercapnia, more recent evidence suggests that hypercapnia could be deleterious, contributing to worsening of the lung injury. PMID- 20303639 TI - Cardiac arrest centres make sense. PMID- 20303640 TI - Impact of transport to critical care medical centers on outcomes after out-of hospital cardiac arrest. AB - BACKGROUND: Post-resuscitation care has emerged as an important predictor of survival from out-of-hospital cardiac arrest (OHCA). In Japan, selected hospitals are certified as Critical Care Medical Centers (CCMCs) based on their ability and expertise. HYPOTHESIS: Outcome after OHCA is better in patients transported to a CCMC compared a non-critical care hospital (NCCH). MATERIALS AND METHODS: Adults with OHCA of presumed cardiac etiology, treated by emergency medical services systems, and transported in Osaka from January 1, 2005 to December 31, 2007 were registered using a prospective Utstein style population cohort database. Primary outcome measure was 1 month neurologically favorable survival (CPC< or =2). Outcomes of patients transported to CCMC were compared with patients transported to NCCH using multiple logistic regressions and stratified on the basis of stratified field ROSC. RESULTS: 10,383 cases were transported. Of these, 2881 were transported to CCMC and 7502 to NCCH. Neurologically favorable 1-month survival was greater in the CCMC group [6.7% versus 2.8%, P<0.001]. Among patients who were transported to hospital without field ROSC, neurologically favorable outcome was greater in the CCMC group than the NCCH group [1.7% versus 0.5%; adjusted odds ratio (OR), 3.39; 95% confidence interval (CI), 2.17-5.29; P<0.001]. In the presence of field ROSC, survival was similar between the groups [43% versus 41%; adjusted OR, 1.09; 95% CI, 0.82-1.45; P=0.554]. CONCLUSIONS: Survival after OHCA of presumed cardiac etiology transported to CCMCs was better than those transported to NCCHs. For OHCA patients without field ROSC, transport to a CCMC was an independent predictor for a good neurological outcome. PMID- 20303641 TI - A pilot study comparing efficacy of a cervical intraepithelial neoplasia Excisor with loop electrosurgical excision procedure. AB - OBJECTIVE: To determine whether the proportion of incomplete resection of cervical intraepithelial neoplasia (CIN 1-3) may be reduced by CIN Excisor compared with loop excision of the transformation zone (LLETZ). STUDY DESIGN: A prospective trial during a 2-year period at a district general hospital in London, United Kingdom, including 420 women scheduled for treatment due to CIN, after colposcopy guided biopsy results. This study was expected to demonstrate a statistically significant difference (p<0.05) in the proportion of women with clear histopathological resection margins after treatment with CIN Excisor compared with LLETZ. Chi-square or Fisher's exact test were used to compare histopathological resection margins in the CIN Excisor and LLETZ groups. RESULTS: Overall, there is strong evidence of a difference in the proportion of histopathological specimens with clear resection margins for the CIN Excisor group, compared with the LLETZ group (201/210, 95.7% versus 180/210, 85.7%: p<0.001). Sub-analysis within the two groups, of the proportion of histopathological specimens with clear resection margins in relation to CIN grades, revealed a statistically significant difference in favour of the CIN Excisor group for CIN 1 (99/103, 96.1% versus 82/95, 86.3%: p=0.01), and CIN 2 (73/77, 94.8% versus 68/80, 85%: p=0.04). There is a numerical difference in the proportion of clear resection margins in favour of the CIN Excisor for CIN 3 (29/30, 96.7% versus 30/35, 85.7%), but this difference was not statistically significant (p=0.21). Perioperative complications were similar between the two groups. CONCLUSION: CIN Excisor achieved better results than LLETZ for treatment of CIN 1-3 with respect to clear histopathological resection margins. However, further studies including a larger number of women treated for CIN 3 are needed before firm conclusions are drawn. PMID- 20303642 TI - Coagulation versus excision of primary superficial endometriosis: a 2-year follow up. AB - OBJECTIVE: Even the common mild forms of endometriosis can strongly affect quality of life due to dysmenorrhea, dyspareunia, dyschezia, or subfertility. We compared the effectiveness of the two laparoscopic methods, coagulation versus excision, for intraperitoneal superficial endometriosis with regard to recurrence and symptom control. STUDY DESIGN: In a retrospective analysis we evaluated the postoperative follow-up of 79 patients, aged 16-42, with superficial manifestation of endometriosis (median rASRM score 9.2) operated on in the Department of Gynecology and Obstetrics at the Jena University Hospital. Forty three patients were treated by electrocoagulation and 36 underwent sharp excision. Therapy success was evaluated by using a questionnaire after a mean follow-up of 29 months. Patients were interviewed about pain associated with endometriosis such as dysmenorrhea, dyspareunia, dyschezia and possible medical treatment after surgery. We evaluated the number of surgically proven relapses and questionnaire results using a pain score on an ordinal scale (1-5) for the three categories dysmenorrhea, dyspareunia, and dyschezia. RESULTS: Both treatment methods resulted in a low number of endometriosis-related symptoms after surgical intervention and in recurrences of 2.8% in the coagulation group and 18.6% in the excision group. The recurrence rate in the coagulation group was lower (p=0.001). The coagulation group was also presented with a significantly lower postoperative pain score at our long-term follow-up (p=0.0067). CONCLUSION: In cases of superficial endometriosis, laparoscopic surgery achieved low recurrence rates and good symptom control. Compared to sharp excision the use of bipolar electrocoagulation might result in fewer endometriosis-related symptoms as well as fewer relapses with need for surgical re-intervention after a more than 2-year interval. Due to the retrospective, non-randomized character of this study the results should be interpreted carefully. Further prospective studies are needed to assess the value of both surgical approaches in the treatment of endometriosis. PMID- 20303643 TI - Isolated torsion of the fallopian tube in a patient with polycystic ovarian syndrome (PCOS). PMID- 20303644 TI - Signal relay from sensory rhodopsin I to the cognate transducer HtrI: assessing the critical change in hydrogen-bonding between Tyr-210 and Asn-53. AB - Sensory rhodopsin I (SRI) from Halobacterium salinarum mediates both positive and negative phototaxis in a light-dependent manner. SRI photoactivation elicits extensive structural changes which are transmitted to the cognate transducer (HtrI). The atomic structure of the SRI-HtrI complex has not been solved yet and, therefore, details on the interaction which define the binding site between receptor and transducer are missing. The related complex SRII-HtrII from Natronobacterium pharaonis exhibits a hydrogen bond between the receptor Y199 and transducer N54. This bond has been suggested to mediate signal relay in the SRII HtrII system. Our previous results on the SRI-HtrI complex indicated that HtrI N53 forms a hydrogen bond at the cytoplasm-proximity of the membrane. Here, based on kinetic and spectroscopic data, we demonstrate that Y210 of SRI is functionally significant for the signal relay in the SRI-HtrI complex. Each of the tyrosine residues Y197, Y208, Y210 and Y213 were conservatively exchanged for phenylalanine but only the Y210F mutation led to the disappearance of the infrared band of the terminal amide C=O of N53. From this FT-IR spectroscopic result, we conclude that Y210 of SRI and N53 of HtrI interact via a hydrogen bond which is crucial for the signal transfer from the light receptor to the transducer. PMID- 20303645 TI - Progenitor cells harvested from bovine follicles become endothelial cells. AB - Hematopoietic-like colonies develop in post-confluent granulosa cell cultures derived from bovine antral follicles. Previously, we had shown that these colonies gave rise to macrophages. In the present study, we validated the presence of somatic KIT-positive (KIT(+)) progenitor cells in colony-containing granulosa cell cultures. The cultures expressed the progenitor cell markers Sox 2, Oct 3/4, KIT, and alkaline phosphatase in western blot analysis. The successful double immunofluorescence localization of KIT and CD14, CD45, CD133, or VEGF-R2 revealed a specific subpopulation of progenitor cells. Flow cytometry showed that cells doubly positive for KIT and CD14 or CD45 comprised less than 10% of the population. The KIT(+) cells were purified by magnetic selection and differentiated with the hanging drop technique using haematopoietic differentiation medium. Pure cultures of either granulosa cells or endothelial cells were obtained. The spindle-shaped and epithelioid phenotypes indicated endothelial cell heterogeneity of microvascular source. We conclude that progenitor cells are obtained from the follicle harvest, which differentiate into endothelial cells. The cells are relevant for findings to angiogenesis and luteinization of the corpus luteum. PMID- 20303646 TI - Impact of routine second transurethral resection on the long-term outcome of patients with newly diagnosed pT1 urothelial carcinoma with respect to recurrence, progression rate, and disease-specific survival: a prospective randomised clinical trial. AB - BACKGROUND: Transurethral resection (TUR) of bladder tumours is not only mandatory for adequate staging but also crucial in delaying or preventing tumour recurrence and progression. OBJECTIVE: To evaluate the impact of routine second TUR on the long-term outcome of patients with newly diagnosed pT1 urothelial carcinoma. DESIGN, SETTING, AND PARTICIPANTS: Two hundred ten newly diagnosed T1 bladder cancer patients were prospectively randomised to two groups between January 2001 and January 2005. Second TUR was performed within 2-6 wk after the initial resection for the patients of group 1. Second TUR was not done in group 2. All patients (groups 1 and 2) received the first instillation of intravesical chemotherapy within 24h after the initial resection. Urine cytology and follow-up cystoscopy were performed at 3-mo intervals for the first year, biannually for the second year, and annually thereafter. All patients were followed until death or a minimum of 54 mo. MEASUREMENTS: This study recorded recurrence, progression rate, and disease-specific survival. RESULTS AND LIMITATIONS: The mean follow-up period was 66.1 mo without a significant difference between the groups. Residual tumour was detected histopathologically in 35 of 105 patients in group 1. Of these patients, eight had upper-stage (pT2) disease. Recurrence was observed in 37 of the 93 patients in group 1 and 70 of the 98 patients in group 2. Median recurrence-free survival was 47 mo for group 1 compared with 12 mo for group 2. Progression was observed in 6.5% of patients for group 1 compared to 23.5% of patients for group 2 (p=0.001). Median progress-free survival was 73 mo for group 1 compared to 53.5 mo for group 2. The overall survival rate was 67.7% and 64.3% in groups 1 and 2, respectively (log-rank test result: 0.363). Only 5 of the 30 patients in group 1 died of cancer compared to 11 of the 35 patients in group 2 (p=0.038). CONCLUSIONS: We have clearly shown that second TUR, which is performed only after complete first TUR, has significantly decreased the recurrence and progression rates in patients with newly diagnosed T1 disease compared to patients with T1 disease but with no second TUR. This study once more underscores the effect of TUR, which is usually underappreciated. PMID- 20303647 TI - The relationship between actigraphically defined sleep disturbance and REM sleep behaviour disorder in Parkinson's Disease. AB - AIM: In this study, we sought to evaluate the utility of actigraphy for examining symptoms of rapid eye movement sleep behaviour disorder (RSBD). METHODS: Twenty two patients with idiopathic Parkinson's Disease (mean age=63.4 years, SD=7.5) underwent neurological assessment and completed sleep diaries, self-report sleep questionnaires and 2-weeks of actigraphy. They also completed the rapid eye movement sleep behavior disorder questionnaire and were classified as screening negative (RSBD-, n=9) or positive (RSBD+, n=13) for RSBD according to published criteria. Key outcome data were the number of wake bouts and duration of arousals during the sleep interval as determined by actigraphy. RESULTS: Patients classified as RSBD+ demonstrated a higher number of wake bouts than those who were RSBD- (p=0.011). CONCLUSIONS: These results suggest that actigraphy may be a viable tool to assist in the early identification of RSBD. In turn, this could guide early intervention approaches. PMID- 20303648 TI - Downregulation of RhoB GTPase confers resistance to cisplatin in human laryngeal carcinoma cells. AB - Acquired resistance to cisplatin represents a major obstacle to an efficient chemotherapy. We found downregulation of RhoB expression in cisplatin-resistant tumor cell lines from different origin. In cisplatin-resistant laryngeal carcinoma subline overexpression of farnesylated or geranylgeranylated RhoB increased cisplatin-induced cell death, while silencing of RhoB expression diminished sensitivity of parental HEp-2 cells via decreased cellular accumulation of cisplatin. However, since RhoB silencing in additional tumor cell lines did not alter their sensitivity to cisplatin, we can assume that RhoB downregulation does not provide general protective role in cell response to cisplatin. Nevertheless, gene therapy involving restoration of RhoB expression might improve the efficiency of cisplatin treatment, especially in patients with laryngeal carcinoma that acquired resistance to this chemotherapeutic drug. PMID- 20303650 TI - A tandem scFv-based fusion protein and its enediyne-energized analogue show intensified therapeutic efficacy against lung carcinoma xenograft in athymic mice. AB - Gelatinases play important roles in tumor progression and are abundantly expressed in a variety of malignant tumors. Antibody targeting gelatinases is a possible avenue to fight against cancer. However, antibody alone can not achieve curative efficacy. Herein, we demonstrated the intensified targeting therapy of a tandem scFv-based fusion protein and its enediyne-energized analogue against gelatinases-overexpressed tumor. A fusion protein dFv-LDP, comprising a tandem scFv of anti-gelatinases linked to the apoprotein (LDP) of lidamycin, was generated and showed strong tumor targeting capability in three different tumor xenografts. In PG-BE1 lung carcinoma xenograft, the tumor inhibition rate was 77.5% by dFv-LDP versus 94.2% by dFv-LDP-AE, the product of dFv-LDP assembled with the active enediyne chromophore (AE) of lidamycin. Moreover, the combination of dFv-LDP with dFv-LDP-AE further augmented the therapeutic efficacy, producing initial tumor shrinkage in five of six mice. The microvessel density (P<0.05) and proliferation index (P<0.05) were also stepwise decreased in groups of dFv-LDP, dFv-LDP-AE and the combination. In conclusion, our results demonstrated that the antibody-based therapy against gelatinases was stepwise intensified in use of dFv LDP, dFv-LDP-AE and dFv-LDP plus dFv-LDP-AE, and indicated that the combination of an antibody with its drug-armed analogue might be of interest as a new approach to augment antitumor efficacy. PMID- 20303651 TI - Occurrence and risks of triclosan and triclocarban in the Pearl River system, South China: from source to the receiving environment. AB - We investigated two commonly used antimicrobial agents triclosan (TCS) and triclocarban (TCC) in the Pearl River system in China (i.e., Liuxi, Zhujiang and Shijing Rivers) and four sewage effluents during dry and wet seasons. The median values for TCS and TCC were the highest in the surface water and sediments of the Shijing River, followed by the Zhujiang River and Liuxi River. Screening level risk assessment using the risk quotient (RQ) method showed that TCS and TCC in surface water posed median risks in the Zhujiang and Liuxi Rivers (RQs: 0.28-0.62 for TCS, and 0.15-0.80 for TCC) and high risks in the Shijing River (RQs: 5.15 9.55 for TCS, and 3.32-5.83 for TCC). Higher risks (RQs: 3.63-28.47 for TCS, and 3.13-24.54 for TCC) were found in the sediments than in surface water of the Pearl River system. The four sewage effluents and Shijing River as well as other urban streams in Guangzhou metropolitan area were identified as the sources of the two compounds in the main river Zhujiang River. The mass inventories of TCS and TCC in the Pearl River system indicate that the sediments are not only an important sink but also a potential source for the two compounds in surface water. PMID- 20303649 TI - MUC4 down-regulation reverses chemoresistance of pancreatic cancer stem/progenitor cells and their progenies. AB - The present study was undertaken to estimate the therapeutic benefit to down regulate the MUC4 mucin for reversing chemoresistance of pancreatic cancer (PC) stem/progenitor cells and their progenies. The results have revealed that MUC4 mucin is overexpressed in CD133(+) and CD133(-) pancreatic cells (PCs) detected in patient's adenocarcinoma tissues while no significant expression was seen in normal pancreatic tissues. The gain- and loss-of-function analyses have indicated that the overexpression of MUC4 in PC lines is associated with a higher resistance to the anti-proliferative, anti-invasive and apoptotic effects induced by gemcitabine. Importantly, the treatment of the MUC4-overexpressing CD18/HPAF Src cells with gemcitabine resulted in an enrichment of the side population (SP) cells expressing CD133 while the total PC cells including non-SP cells detected in MUC4 knockdown CD18/HPAF-shMUC4 cells were responsive to the cytotoxic effects induced by gemcitabine. These data suggest that the MUC4 down-regulation may constitute a potential therapeutic strategy for improving the efficacy of gemcitabine to eradicate the total PC cell mass, and thereby preventing disease relapse. PMID- 20303652 TI - Study of organic matter during coagulation and electrocoagulation processes: application to a stabilized landfill leachate. AB - Organic matter contained in leachates appears to be a relevant indicator of waste evolution. Among the physico-chemical treatments applied to stabilize leachates, coagulation-flocculation is considered a classical process and electrocoagulation can be developed. Electrocoagulation tests were carried out in a laboratory pilot using aluminium plates and compared to classical coagulation-flocculation with aluminium ions and to electrolysis alone. The leachate used in this study came from the landfill of Crezin (Limoges, France) and it presented low biodegradability and high concentration of macromolecules. To assess the efficiency of the chemical and electrochemical processes, we specifically studied Organic Matter (OM) by using two protocols: adsorption on XAD resins and fractionation by ultrafiltration. Biodegradable Dissolved Organic Carbon (BDOC) measurements were applied to the fractions extracted by XAD resins and were also used as an indicator of the efficiency of the treatments. Residual organic matter concentration was the same for the two processes but its composition appeared different after electrocoagulation: a higher percentage of small hydrophilic organic molecules which seemed to be less biodegradable than the initial organic matter was observed. PMID- 20303653 TI - Experimental design approach applied to the elimination of crystal violet in water by electrocoagulation with Fe or Al electrodes. AB - An experimental design methodology was applied to evaluate the decolourization of crystal violet (CV) dye by electrocoagulation using iron or aluminium electrodes. The effects and interactions of four parameters, initial pH (3-9), current density (6-28 A m(-2)), substrate concentration (50-200 mg L(-1)) and supporting electrolyte concentration (284-1420 mg L(-1) of Na(2)SO(4)), were optimized and evaluated. Although the results using iron anodes were better than for aluminium, the effects and interactions of the studied parameters were quite similar. With a confidence level of 95%, initial pH and supporting electrolyte concentration showed limited effects on the removal rate of CV, whereas current density, pollutant concentration and the interaction of both were significant. Reduced models taking into account significant variables and interactions between variables have shown good correlations with the experimental results. Under optimal conditions, almost complete removal of CV and chemical oxygen demand were obtained after electrocoagulation for 5 and 30 min, using iron and aluminium electrodes, respectively. These results indicate that electrocoagulation with iron anodes is a rapid, economical and effective alternative to the complete removal of CV in waters. Evolutions of pH and residual iron or aluminium concentrations in solution are also discussed. PMID- 20303655 TI - Removal of Cd(II) from aqueous solution with activated Firmiana Simplex Leaf: behaviors and affecting factors. AB - Cadmium pollution is known to cause severe public health problems. This study is intended to examine the effect of an activated Firmiana Simplex Leaf (FSL) on the removal of Cd(II) from aqueous solution. Results showed that the active Firmiana Simplex Leaf could efficiently remove Cd(II) from wastewater due to the preservation of beneficial groups (amine, carboxyl, and phosphate) at a temperature of 250 degrees C. The adsorbent component, dosage, concentration of the initial solute, and the pH of the solution were all found to have significant effects on Cd(II) adsorption. The kinetic constants were predicted by pseudo first-order kinetics, and the thermodynamic analysis revealed the endothermic and spontaneous nature of the adsorption. FT-IR and XRD analyses confirmed the strong adsorption between beneficial groups and cadmium ions, and the adsorption capacity was calculated to be 117.786 mg g(-1) according to the Langmuir isotherm. PMID- 20303654 TI - Removal of malachite green from aqueous solution by activated carbon prepared from the epicarp of Ricinus communis by adsorption. AB - The use of low-cost, locally available, highly efficient and eco-friendly adsorbents has been investigated as an ideal alternative to the current expensive methods of removing dyes from wastewater. This study investigates the potential use of activated carbon prepared from the epicarp of Ricinus communis for the removal of malachite green (MG) dye from simulated wastewater. The effects of different system variables, adsorbent dosage, initial dye concentration, pH and contact time were investigated and optimal experimental conditions were ascertained. The results showed that as the amount of the adsorbent increased, the percentage of dye removal increased accordingly. Optimum pH value for dye adsorption was 7.0. Maximum dye was sequestered within 50 min of the start of every experiment. The adsorption of malachite green followed the pseudo-second order rate equation and fits the Langmuir, Freundlich, Dubinin-Radushkevich (D-R) and Tempkin equations well. The maximum removal of MG was obtained at pH 7 as 99.04% for adsorbent dose of 1 g 50 mL(-1) and 25 mg L(-1) initial dye concentration at room temperature. Activated carbon developed from R. communis can be an attractive option for dye removal from diluted industrial effluents since test reaction made on simulated dyeing wastewater showed better removal percentage of MG. PMID- 20303656 TI - Genotoxicity effect of nitrobenzene on soybean (Glycine max) root tip cells. AB - Nitrobenzene is a synthetic compound widely used in industry which can lead to environmental pollution. While the toxicity and carcinogenicity of nitrobenzene on humans and animals have been studied, less is known about its genotoxicity to plants. In this study, the genotoxic effects of nitrobenzene were investigated with growing soybean seedlings in solution culture. Compared with the control, the growth of soybean seedlings (taproot length, longest lateral root length and lateral roots number) decreased and showed statistics difference at nitrobenzene test concentration of 50 and 100mg/L. Micronucleus, chromosomal bridge and others chromosomal aberrations were observed in soybean root tip cells exposed to nitrobenzene. Frequency of chromosomal aberrations increased linearly with nitrobenzene test concentration between 5 and 50mg/L and decreased at 100mg/L which showed significant difference between control and 25mg/L or higher test concentration. Results of the present study suggest that nitrobenzene has genotoxicity on soybean root tip cells. The mechanism of genotoxicity of NB needs further study. It is concluded that high environmental levels of nitrobenzene in rivers, lakes and dam waters are hazardous to aquatic species and to irrigated plants. PMID- 20303657 TI - Biosorption of Cr(VI) by coconut coir: spectroscopic investigation on the reaction mechanism of Cr(VI) with lignocellulosic material. AB - In this study, the removal mechanism of Cr(VI) from water by coconut coir (CC) was investigated using X-ray photoelectron spectroscopy (XPS), Cr K-edge X-ray absorption near edge structure (XANES) and FTIR spectroscopy. The results showed that, upon reaction with CC at pH 3, Cr(VI) was reduced to Cr(III), which was either bound to CC or released back into solution. As revealed by the FTIR spectra of CC before and after reacting with Cr(VI), the phenolic methoxyl and hydroxyl groups of lignin in CC are the dominant drivers of Cr(VI) reduction, giving rise to carbonyl and carboxyl groups on CC. These functional groups can subsequently provide binding sites for Cr(III) resulting from Cr(VI) reduction. In conjunction with forming complexes with carbonyl and carboxyl groups, the formation of Cr(III) hydroxide precipitate could also readily occur as revealed by the linear combination fitting of the Cr K-edge XANES spectrum using a set of reference compounds. The phenolic groups in lignin are responsible for initiating Cr(VI) reduction, so lignocellulosic materials containing a higher amount of phenolic groups are expected to be more effective scavengers for removal of Cr(VI) from the environment. PMID- 20303658 TI - Removal of arsenate from water by using an Fe-Ce oxide adsorbent: effects of coexistent fluoride and phosphate. AB - The Langmuir two-site equation, X-ray photoelectron spectroscopy, and extended X ray absorption fine structure spectroscopy have been employed to study the competitive behaviors of fluoride (F) and phosphate (P) in relation to arsenate adsorption on an Fe-Ce adsorbent as well as the mechanisms involved. The two-site isotherm revealed the presence of two kinds of adsorption sites with different binding affinities for arsenate. Both the total and low-binding-energy maximum adsorption capacities (Q and Q(1)) of arsenate decreased significantly even at a molar ratio of As/P=1:0.1. The coexistence of F, only influenced the total Q of arsenate at high simultaneous F concentrations. The fact that Fe-Ce released 0.15 0.24 mmol sulfate for every mmol arsenate adsorbed suggested that, while sulfate groups might have played a role for adsorption, surface hydroxyl groups should be the major active sites. The XPS results indicated that arsenate and P are mainly adsorbed through the substitution of Fe surface active sites, while F is mainly adsorbed through substitution of Ce surface active sites. The As k-edge EXAFS data show that the second peak of Fe-Ce after arsenate adsorption is As-Fe shell, which further supported that arsenate adsorption occurs mainly at the Fe surface active sites. PMID- 20303659 TI - Bioadsorption of methyl violet from aqueous solution onto Pu-erh tea powder. AB - Chinese unique Pu-erh tea powder (PTP), with leached active ingredients, was used here to adsorb methyl violet (MV), a cationic dye. The effects of several variables on the removal of methyl violet were studied at 25 degrees C, including pH value, contact time, quantity of the adsorbent, initial concentration, and particle size of the adsorbent. The results showed that the particle size of the adsorbent significantly affected the adsorption process, and the nano-sized PTP particles had the best adsorption efficiency. The equilibrium data was analyzed using Langmuir, Freundlich, and Tempkin isotherms models. The pseudo-second-order kinetics model best explained the MV adsorption by PTP of any particle size. The intra-particle diffusion model was also used to analyze the adsorption process, and it was found that smaller adsorbent particles had a bigger boundary layer effect. PMID- 20303660 TI - Electron-accepting potential of solvents determines photolysis rates of polycyclic aromatic hydrocarbons: experimental and density functional theory study. AB - Photochemical behaviour of polycyclic aromatic hydrocarbons (PAHs) is strongly dependent on the physical and chemical nature of the media in/on which they exist. To understand the media effects, the photolysis of phenanthrene (PHE) and benzo[a]pyrene (BaP) in several solvents was investigated. Distinct photolysis rate constants for PHE and BaP in the different solvents were observed. Some theoretical parameters reflecting the solvent properties were computed and employed to explain the solvent effects. Acetone competitively absorbed light with PHE and BaP, and the excited acetone molecules played different roles for the photodegradation of PHE and BaP. The photolysis rate constants of PHE and BaP in hexane, isopropanol, ethanol, methanol, acetonitrile and dichloromethane were observed to correlate with the electron-accepting potential of the solvent molecules. Absolute electronegativity of the solvents linearly correlated with the photolytic activity (log k) of the PAHs significantly. The results are important for better understanding the photodegradation mechanism of PAHs in different media. PMID- 20303661 TI - Pretreatment of petrochemical wastewater by coagulation and flocculation and the sludge characteristics. AB - In the present study, coagulation-flocculation was investigated as a pretreatment process for the treatment of purified terephthalic acid (PTA) wastewater. The effect of various inorganic and organic coagulants on the treatment of wastewater collected from flow equalization tank of an effluent treatment plant was studied. The settling and filtration characteristics of the sludge were also studied. The jar tests revealed that the wastewater was best treated when 3000 mg l(-1) of ferric chloride was dosed at pH 5.6. At optimum conditions, COD of the wastewater was reduced by 75.5%. The results of the gravity filtration of the treated wastewater showed that the addition of cationic polyacrylamide (175 mg l(-1)) to ferric chloride coagulation improved the filtration characteristics and reduced the specific cake resistance. Scanning electron microscopy and energy dispersive spectroscopy studies were also conducted to know the sludge structure and composition, respectively. Thermal analysis of the sludge showed that the oxidation of the sludges in the present study is a three step process. However, with the addition of C-PAA to ferric chloride coagulation system, the oxidation was found to be a two step process. PMID- 20303662 TI - Adsorption property and mechanism of composite adsorbent PMAA/SiO2 for aniline. AB - In this paper, functional monomer methacrylic acid (MAA) was grafted onto the surface of silica gel particles using 3-methacryloxypropyl trimethoxysilane (MPS) as intermedia, and grafting particles PMAA/SiO(2) were prepared. The adsorption properties and mechanism of PMAA/SiO(2) towards aniline were researched through batch and column adsorption methods. The experimental results showed that PMAA/SiO(2) possesses strong adsorption ability for aniline with interaction of hydrogen bond. The saturated adsorption amount could reach up to 140 mg g(-1). The empirical Langmuir isotherm was found to agree well with the equilibrium adsorption data. pH and temperature were found to have great influence on the adsorption amount. Finally, PMAA/SiO(2) was observed to possess excellent reusability properties as well. PMID- 20303663 TI - Enhancing the sorption capacity of CTMA-bentonite by simultaneous intercalation of cationic polyacrylamide. AB - The saturated level of cationic exchange capacity (CEC) of bentonite by organic cations can significantly influence the sorption capacity of the resulting organobentonites. In this work cationic polyacrylamide (CPAM) was applied to saturate part of the CEC of the cetyltrimethylammonium (CTMA) modified bentonite, with the aim to enhance their sorption capacity. XRD was applied to investigate the basal spacings of the organobentonites with and without CPAM, and the sorption characteristics of the organobentonites towards phenol and nitrobenzene to CTMA-bentonite was also studied. The XRD characterization results showed that the resulting organobentonites (C/P-Bt) had larger basal spacings than the CTMA modified bentonite (C-Bt), which indicated that both CPAM and CTMA could intercalate into the interlayer spaces of C/P-Bt. The saturated CEC of C/P-Bt increased with the intercalated amounts of CPAM. The sorption coefficients (K(d)) of phenol and nitrobenzene on C/P-Bt were shown to first increase with the saturated CEC until the maximum, and then began to decrease as the saturated CEC further increased. The maximum increase of K(d) reached 41% and 23% for phenol and nitrobenzene, respectively, which could be ascribed to the enhanced affinity of the adsorbed CTMA aggregates towards the sorbates. Results of this work showed that the simultaneous intercalation of CPAM could be a novel method to enhance the sorption capacity of the traditional organobentonites. PMID- 20303664 TI - Influence of ZrO2 properties on catalytic hydrodechlorination of chlorobenzene over Pd/ZrO2 catalysts. AB - Pd/ZrO(2) catalysts using different ZrO(2) as supports were prepared using the deposition-precipitation method and were characterized by X-ray diffraction, transmission electron microscopy, X-ray photoelectron spectroscopy, N(2) adsorption, temperature programmed reduction, H(2) chemisorption and measurement of surface hydroxyl group. Catalytic hydrodechlorination (HDC) of chlorobenzene was used to evaluate the activity and stability of the catalyst. The results showed that ZrO(2) support calcined at 300 degrees C was amorphous in nature, whereas ZrO(2) supports calcined at 500 and 600 degrees C consisted of both monoclinic and tetragonal phases. In addition, increasing calcination temperature led to the decrease of specific surface area and surface hydroxyl group content of the ZrO(2) support. For temperature programmed reduction of PdO/ZrO(2) samples, two H(2) consumption peaks with varied reduction temperature were distinctly observed, implying the existence of different Pd species in Pd/ZrO(2) catalysts. In addition, Pd/ZrO(2) catalyst with ZrO(2) calcined at 500 degrees C had a relatively higher content of Pd species with strong metal-support interaction than other catalysts. For catalytic HDC of chlorobenzene, Pd/ZrO(2) catalyst with ZrO(2) support calcined at 500 degrees C exhibited a higher initial activity and stability as compared to other catalysts, indicative of a strong dependence of the catalytic behavior of the Pd/ZrO(2) catalyst on the support properties for catalytic HDC of chlorobenzene. PMID- 20303666 TI - Identification of magnetic properties of few nm sized FePt crystalline particles by characterizing the intrinsic atom order using aberration corrected S/TEM. AB - Hard-magnetic nanomaterials like nanoparticles of FePt are of great interest because of their promising potential for data storage applications. The magnetic properties of FePt structures strongly differ whether the crystal phases are face centered cubic (fcc) or face centered tetragonal (fct). We evaluated aberration corrected HRTEM, electron diffraction and aberration corrected HAADF-STEM as methods to measure the chemical degree of order S that describes the ordering of Pt and Fe atoms within the crystals unit cells. S/TEM experiments are accompanied by image calculations. The findings are compared with results obtained from X-ray diffraction on a FePt film. Our results show that STEM is a reasonable fast approach over HRTEM and electron diffraction to locally determine the chemical degree of order S. PMID- 20303665 TI - How do changes in pain severity levels correspond to changes in health status and function in patients with painful diabetic peripheral neuropathy? AB - The current analysis compares changes in pain with changes in function and health status in individuals with painful diabetic peripheral neuropathy (DPN). The post hoc analysis is based on a 12week, multinational, placebo-controlled trial of pregabalin in which 401 patients were randomized to treatment. Study measures included the Brief Pain Inventory short-form (BPI-sf), EQ-5D and other patient reported outcomes. Cutpoints were derived on the BPI-sf 0-10 average pain numeric rating scale [NRS] to classify pain grades of "mild" (1-3), moderate (4-6) and severe (7-10), adjusting for geographical regions where data were collected. Two different metrics were used to classify the importance of change in pain severity from baseline to 12weeks: changes in pain severity grades (defined by cutpoint categories) and percent reduction in the NRS (categories ranging from 0-9% to 50%). An improvement in one pain grade or a 30% reduction in the NRS served as determinants of a clinically important difference. Patients with a one-grade reduction in pain severity, either from "severe-to-moderate" or "moderate-to mild," had a 3-point improvement the BPI-sf Pain Interference Index (PII; a composite measure of function); a reduction from "severe-to-mild" pain corresponded to a 6-point improvement in the PII. Similarly, a reduction in the NRS of 30% and 50% corresponded to a 3-point and a 5-point improvement in the PII, respectively. Changes in pain were also associated with changes in health status. Results suggest that patients whose pain is not reduced to a mild level of severity can still experience clinically important changes in function and health status. PMID- 20303667 TI - Acaricidal activity of Satureja thymbra L. essential oil and its major components, carvacrol and gamma-terpinene against adult Hyalomma marginatum (Acari: Ixodidae). AB - The acaricidal activity of a volatile essential oil hydrodistillate of Satureja thymbra L. (Lamiaceae) and its major constituents, carvacrol and gamma-terpinene, were evaluated against field-collected unfed adult Hyalomma marginatum. The distillate was tested against this tick species at 5, 10, 20, and 40 microL/L while the two major components were each tested at 10 microL/L. Generally, tick mortality to the S. thymbra distillate increased with concentration and exposure time. Ticks exposed to vapors from cotton wicks containing at least 40 microL/L resulted in complete (100%) mortality at 3h. The lower concentrations provided >or=90% mortality at 3h post treatment with complete mortality at 24h. Knockdown was observed only in the carvacrol and gamma-terpinene treatments. Ticks exposed to carvacrol-treated wicks produced >93% knockdown at 3h but at 24h approximately 57% were dead. The gamma-terpinene treatment produced >or=90% knockdown at 105 min through 3h but at 24h only about 87% of the ticks were dead. PMID- 20303668 TI - An intraoral neurocranial vertical distractor appliance provides unique treatment for Tourette's syndrome and resolves comorbid neurobehavioral problems of obsessive compulsive disorder. AB - Evidence has existed for many years that individuals with Tourette's syndrome (T.S.) have associated neurobehavioral comorbid disorders. Though these disorders are not necessary to give a definitive diagnosis for Tourette's syndrome, many patients present with clinical signs of additional problems. Many believe that Tourette's is a neuropsychiatric disorder with symptoms originating from the brain or basal ganglia. Some of these coexisting conditions include attention deficit hyperactive disorder (ADHD), obsessive compulsive disorder (OCD), depression, sleep disorders, and enuresis. We hypothesize that an intraoral device can be utilized to eliminate these associated comorbid neurobehavioral signs and symptoms. Use of this device, called a neurocranial vertical distractor (NCVD), results in the elimination of unwanted neurobehavioral disorders via normally existing trigeminoreticular fibers and tracts (Fig. 1). PMID- 20303669 TI - Gene-environment mismatch in decompression sickness and air embolism. AB - Decompression sickness causes injury and death in SCUBA divers when air bubbles obstruct the flow of blood. Platelets aggregate in response to gas and promote inflammation. Inflammation in decompression sickness may have its origin in the innate immune system's response to pathogens. Bubbles are often found in tissues during gas-forming infections and in infection-prone states. In these diseases, intravascular gas offers a signal of infection to immune cells. Platelet activation by gas may often accompany a beneficial immune response to pathogens. Pathologic bubble-platelet interaction in decompression illness may be an example of gene-environment mismatch. PMID- 20303670 TI - Role of radiation dose in the risk of secondary leukemia after a solid tumor in childhood treated between 1980 and 1999. AB - PURPOSE: The purpose of this study was to estimate the risk of secondary leukemia as a function of radiation dose, taking into account heterogeneous radiation dose distribution. METHODS AND MATERIALS: We analyzed a case-control study that investigated the risk of secondary leukemia and myelodysplasia after a solid tumor in childhood; it included 61 patients with leukemia matched with 196 controls. Complete clinical, chemotherapy, and radiotherapy histories were recorded for each patient in the study. Average radiation dose to each of seven bone marrow components for each patient was incorporated into the models, and corresponding risks were summed up. Conditional maximum likelihood methods were used to estimate risk parameters. RESULTS: Whatever the model, we failed to evidence a role for the radiation dose to active bone marrow in the risk of later leukemia, myelodysplasia, or myeloproliferative syndrome, when adjusting for epipodophyllotoxin and anthracycline doses. This result was confirmed when fitting models that included total dose of radiation delivered during radiotherapy, when fitting models taking into account dose per fraction, and when restricting the analysis to acute myeloid leukemia. CONCLUSIONS: In contrast to results found in similar studies that included children treated before the use of epipodophyllotoxins, this study failed to show a role for radiotherapy in the risk of secondary leukemia after childhood cancer in children treated between 1980 and 1999. This discrepancy was probably due to a competitive mechanism between these two carcinogens. PMID- 20303671 TI - Keeping the memory of influenza viruses. AB - Protection against pathogens is mediated by both humoral responses (neutralizing antibodies) and cellular immunity, both CD4+ and CD8+ cells. In the case of influenza viruses, circulating strains contain both variable and conserved T and B cell epitopes that are challenged after vaccination and/or infection. During infection, the role of T cells is to prevent viral dissemination in the organism by killing the infected cells and helping B cell antibody production to neutralize the virus. The threat of influenza virus increases the preparedness of protective immunity to pandemic and seasonal infection by vaccination. Several questions remain that need to be further addressed for the future development of innovative and rapidly efficient vaccines strategies. Firstly, what are the correlates of long-term protection (antibodies and/or T cells) against variant strains of influenza? How does the individual factors (age, natural immunity, vaccination and/or infection history) influence the generation and maintenance of memory cells? What are the factors allowing the maintenance of immune memory (regular contact with the pathogen or re-vaccination)? Secondly, what is the nature and quality (function / phenotype / location) of memory B and T cells? Finally, is it necessary to induce and maintain immunological memory against conserved proteins and/or to re-vaccinate against viral variants? What would be the consequences of repeated vaccination? These questions remain a subject of debate that will be further discussed. Since immunological memory is the cornerstone of vaccination, it is essential that we have a better understanding of its generation and maintenance over time as well as its contribution to recall responses during pandemics or after vaccination. PMID- 20303672 TI - Predictive factors of severe disease secondary to falciparum malaria among travelers. AB - OBJECTIVES: To identify independent risk factors of severe falciparum malaria among travelers to endemic regions. MATERIALS AND METHODS: A retrospective study on imported malaria into metropolitan France. The World's Health Organization severity criteria were used to classify malarial episodes. RESULTS: Nine hundred and twenty-one malarial cases were studied; 81 were severe. Independent risk factors of severe malaria were aged above 40 years, high level of parasitized erythrocytes (more than 4%), parasite acquisition in the south-eastern asian region, infection with a chloroquine resistant Plasmodium falciparum (P. falciparum) phenotype and a self administered antimalarial treatment. CONCLUSION: This study points out two particularly interesting results: severe malaria is significantly associated with the infection by a chloroquine resistant P. falciparum phenotype and with the parasite's acquisition in the south-eastern asian region. PMID- 20303673 TI - [Influenza viruses: short symposium]. PMID- 20303674 TI - A 2010 update on occult hepatitis B infection. AB - Occult hepatitis B virus infection is a challenging issue whose virological and clinical relevance has been a source of long-lasting debate. By definition, OBI is characterized by the persistence of HBV-DNA in the liver tissue (and in some cases also in the serum) in absence of HBsAg. According to the HBV serological profile, OBI may be antibody (anti-HBc alone or together with anti-HBs) positive (seropositive OBI) or antibody negative (seronegative OBI). OBI is a complex biological entity with possible relevant clinical implications, mainly related to the intrahepatic persistence of viral cccDNA and to a strong suppression of viral replication and gene expression. Clinical observations suggest that OBI carriers may be a source of HBV transmission through blood transfusion or orthotopic liver transplantation (OLT). The state of suppression of viral replication and gene expression may be discontinued when an immunosuppressive status occurs, leading to typical hepatitis B with severe - and some times - fulminant course. The long lasting persistence of the virus in the liver may provoke a very mild but continuing necro-inflammation that (if other causes of liver damage cohexist) may contribute over time to the progression of the chronic liver damage towards cirrhosis. In addition, OBI is supposed to be an important risk factor to HCC development since it maintains the pro-oncogenic properties typical of the overt infection. PMID- 20303675 TI - [Interspecies transmission, adaptation to humans and pathogenicity of animal influenza viruses]. AB - The emergence in 2009 of a novel A(H1N1)v influenza virus of swine origin and the regular occurrence since 2003 of human cases of infection with A(H5N1) avian influenza viruses underline the zoonotic and pandemic potential of type A influenza viruses. Influenza viruses from the wild aquatic birds reservoir usually do not replicate efficiently in humans. Domestic poultry and swine can act as intermediate hosts for the acquisition of determinants that increase the potential of transmission and adaptation to humans, through the accumulation of mutations or by genetic reassortment. The rapid evolution of influenza viruses following interspecies transmission probably results from the selection of genetic variations that favor optimal interactions between viral proteins and cellular factors, leading to an increased multiplication potential and a better escape to the host antiviral response. Whereas influenza viruses usually cause asymptomatic infections in wild aquatic birds, they may be highly pathogenic in other species. Molecular determinants of host-specificity and pathogenesis have been identified in most viral genes, notably in genes that encode viral surface glycoproteins, proteins involved in the viral genome replication, and proteins that counteract the host immune response. However, our knowledge of these numerous and interdependant determinants remains incomplete, and the molecular mechanisms involved are still to be understood. PMID- 20303676 TI - [Seasonal flu]. AB - Seasonal flu is caused by influenza viruses A and B. These enveloped viruses have a genome made up of seven or eight RNA fragments. The different subtypes are determined by the nature of the two surface glycoproteins HA and NA. Seasonal flu is an epidemic wintertime illness occurring in temperate climate zones. Its epidemiology is linked to the great variability of the virus in time, necessitating an alert system that detects dominating circulating variants each year and that determines the vaccination composition. Clinical flu symptoms are not sufficiently specific to allow for diagnosis with virological tests. This is especially true during non-epidemic periods as well as in subjects older than 65 and younger than five. Children are especially vulnerable to influenza virus infections. Hospitalization occurs more frequently, the younger the child. In children younger than two years, the infection can be pauci-symptomatic and is sometimes detected from non-respiratory symptoms such as lethargy, convulsions, and dizziness. In all cases of respiratory syndrome compatible with influenza virus infection in hospitalized subjects, virological flu diagnosis is of utmost interest. Several tools are available to allow for direct viral detection in respiratory specimens: cell culture isolation, antigenic detection, RNA molecular detection. Choice of method is based on the characteristics of the test: sensibility, specificity, speed and ease of realization, and cost. PMID- 20303677 TI - [Role of neuraminidase inhibitors for the treatment of influenza A virus infections]. AB - Oseltamivir and zanamivir are two neuraminidase inhibitors (NAIs) active on A and B influenza viruses. These analogues have been developed from the structure of sialic acid, the neuraminidase (NA) substrate. Resistance to NAIs have been detected. They are mainly associated to mutations located on the NA gene. The use of these antiviral drugs remains low in the context of seasonal flu, even the duration of symptoms can be reduced of one day if an antiviral treatment is started within 48 hours after disease onset. NAIs also present a significant effect when used in postexposition prophylaxis. Resistance, mainly to oseltamivir, have been detected but remained rare until the spontaneous emergence in 2007-2008 winter of a seasonal A(H1N1) variant resistant to this drug. NAIs are also interesting for the treatment of severe flu infections, specially those associated to A(H5N1). Finally, because of the pandemic A(H1N1)2009 virus, NAIs use has largely increased for prophylactic and therapeutic treatment of severe and non severe infections. This large use may be associated to an increased risk of selection of resistant viruses. Up to now, this phenomenon remains fortunately limited but has to be closely monitored. PMID- 20303678 TI - Pituitary gland volume among heroin users stabilised on substitution pharmacotherapy. AB - While long-term heroin addiction is associated with hypothalamus-pituitary adrenal (HPA) axis dysregulation, few studies have used in vivo brain imaging to examine the impact on pituitary gland volume (PGV) or its relationship with substitution pharmacotherapy. We examined 28 heroin users stable on methadone or buprenorphine and 28 healthy controls. Heroin users exhibited larger PGVs than healthy controls, and this was particularly evident among the buprenorphine treated group. These findings indicate that substitution pharmacotherapy may have differential effects on normalising HPA axis activity. PMID- 20303679 TI - Acceptability of a safer injection facility among injection drug users in San Francisco. AB - OBJECTIVE: Research has shown that safer injection facilities (SIFs) are successful at reducing public nuisance and enhancing public health. Since 2007 support for implementation of a SIF in San Francisco has been building. The objective of this study is to assess the acceptability of a SIF among injection drug users (IDUs) in San Francisco. METHODS: IDUs were recruited in San Francisco using targeted sampling and interviewed using a quantitative survey (N=602). We assessed the prevalence of willingness to use a SIF as well as correlates of willingness among this group. RESULTS: Eighty-five percent of IDUs reported that they would use a SIF, three quarters of whom would use it at least 3 days per week. In multivariate analysis, having injected in public and having injected speedballs were associated with intent to use a SIF. The majority of IDUs reported acceptability of many potential rules and regulations of a pilot SIF, except video surveillance, and being required to show identification. CONCLUSIONS: Building on the success of SIFs in various international settings, IDUs in San Francisco appear interested in using a SIF should one be implemented. PMID- 20303680 TI - Localization of avian bornavirus RNA by in situ hybridization in tissues of psittacine birds with proventricular dilatation disease. AB - Proventricular dilatation disease (PDD) of psittacine birds is caused by a number of different genotypes of a novel viral species, avian bornavirus (ABV). Here we present an in situ hybridization (ISH) procedure using digoxigenin-labeled RNA probes for localizing viral genomic and mRNA of ABV-2 and ABV-4 in tissues of affected birds. Out of eleven immunohistochemically positive birds ISH signals were only found in seven. Partial sequencing of the viral genome had shown that four of them were infected with ABV-2, two with ABV-4 and one had a mixed infection with ABV-2 and ABV-4. ISH signals were present in the brain, in the vegetative nerve system, glandular epithelia and smooth muscle cells of the intestinal tract and in cardiomyocytes. Hybridization signals for viral genome were more abundant than signals for mRNA. As the probes were not strictly genotype-specific, four of the birds had hybridization signals with both, the ABV 2 and ABV-4 probes. The signals achieved with the homologous probes were more intense and more abundant than those resulting from heterologous probes. Taken together, the results of this study show that ISH can be used as a tool for localizing ABV sequences in tissues of birds with PDD and confirm the causative role of ABVs by showing viral replication in affected tissues. PMID- 20303681 TI - Herpesviruses and immunity: the art of evasion. AB - Herpesviruses have evolved several effective strategies to counter the host immune response. Chief among these is inhibition of the host MHC class I antigen processing and presentation pathway, thereby reducing the presentation of virus derived epitopes on the surface of the infected cell. This review summarizes the mechanisms used by herpesviruses to achieve this goal, including shut-down of MHC class I molecule synthesis, blockage of proteasome-mediated peptide generation and prevention of TAP-mediated peptide transport. Furthermore, herpesvirus proteins can retain MHC class I molecules in the endoplasmic reticulum, or direct their retrograde translocation from the endoplasmic reticulum or endocytosis from the plasma membrane, with subsequent degradation. The resulting down-regulation of cell surface MHC class I peptide complexes thwarts the ability of cytotoxic T lymphocytes to recognize and eliminate virus-infected cells. The subversion of the natural killer cell response by herpesvirus proteins and microRNAs is also discussed. PMID- 20303682 TI - Viral protein expression and phenotyping of inflammatory responses in the central nervous system of phocine distemper virus-infected harbor seals (Phoca vitulina). AB - The central nervous system (CNS) represents an important target organ of the phocine distemper virus (PDV). The aim of the present study was to characterize pathological changes in the CNS of harbor seals suffering from natural PDV infection. The distribution of virus protein and mRNA was investigated by immunohistochemistry (IHC) and in situ hybridization, respectively. In addition, inflammatory and glial cells were characterized by IHC. Polioencephalitis with glial activation, neuronal death and perivascular mononuclear infiltrations in the cerebral cortex was the main histopathological finding. Inflammatory responses, dominated by CD3(+) T-cells and activated microglia/macrophages were associated with a prominent MHC-II upregulation within the CNS. Viral protein was found predominantly in neurofilament-expressing neurons within inflamed areas as demonstrated by immunohistochemical double-labeling. Morbillivirus nucleo-, phospho-, matrix-, fusion- and hemagglutinin-proteins were found in CNS-lesions. The expressions of viral matrix- and fusion-proteins were reduced in severely inflamed plaques. Comparison of viral protein and mRNA expression revealed a diminished amount of viral phosphoprotein preferentially associated with perivascular inflammation. In summary, CNS-lesions in PDV-infected seals are similar to canine distemper virus-induced acute polioencephalitis in dogs and measles virus inclusion body polioencephalitis in men, respectively. PMID- 20303683 TI - Differential expression of mRNAs encoding BMP/Smad pathway molecules in antral follicles of high- and low-fecundity Hu sheep. AB - The Hu sheep is world-famous for its hyper-prolificacy and the bone morphogenetic protein (BMP)/Smad pathway and several other closely related molecules (GDF9, TGF betaRI) have been shown to have a close relationship with reproduction in sheep. In order to investigate the mechanism of high fecundity in Hu sheep and its relationship with the BMP/Smad pathway, 147 Hu sheep were blood sampled for detection of the FecB mutation (A746G) in the BMPRIB gene by PCR-SSCP, and sixteen adult Hu ewes classified as either high-fecundity (HF) or low-fecundity (LF) animals were sacrificed for tissue and antral follicle sampling. The tissue distribution patterns of mRNAs encoding BMP/Smad pathway molecules including BMPs (BMP2, BMP4, BMP6, BMP7 and BMP15), BMP receptors (BMPRIA, BMPRIB and BMPRII), intracellular transducers (Smad1, Smad5 and Smad4) and closely related molecules (GDF9 and TGF-betaRI) were detected by RT-PCR and the gene expression levels in antral follicles were investigated by real-time PCR. The results showed that all experimental animals were homozygous for the BMPRIB (A746G) mutation, and all detected genes related to the BMP/Smad pathway and GDF9 and TGF-betaRI were expressed in the ovary. In addition, BMP4, BMPRIB, BMPRII, Smad4, GDF9 and TGF betaRI mRNAs were more abundant in the antral follicles of HF animals than those of LF animals (P<0.05), but BMP15 mRNA was less abundant (P<0.01). This suggests that there could be an unidentified genetic mutation in BMPRIB, or other unidentified genes and unknown factors, which controls ovarian number by changing the expression patterns of genes known to regulate ovulation rate via the BMP/Smad pathway and closely related molecules (GDF9 and TGF-betaRI). PMID- 20303684 TI - Caution! All data are not created equal: The hazards of using National Weather Service data for calculating accumulated degree days. AB - An increasing number of anthropological decomposition studies are utilizing accumulated degree days (ADD) to quantify and estimate the post-mortem interval (PMI) at given decompositional stages, or the number of ADD required for certain events, such as tooth exfoliation, to occur. This study addresses the utility of retroactively applying temperature data from the closest National Weather Service (NWS) station to these calculations as prescribed in the past. Hourly temperature readings were collected for 154 days at a research site in Farmington, AR between June 30 and December 25, 2008. These were converted to average daily temperatures by calculating the mean of the 24 hourly values, following the NWS reporting procedure. These data were compared to comparable data from the Owl Creek and Drake Field NWS stations, the two closest to the research site, located 5.7 and 9.9km away, respectively. Paired samples t-tests between the research site and each of the NWS stations show significant differences between the average daily temperature data collected at the research station, and both Owl Creek (2.0 degrees C, p<0.001) and Drake Field (0.6 degrees C, p<0.001). When applied to a simulated recovery effort, the further NWS station also proved to represent the better model for the recovery site. Using a published equation for estimating post-mortem interval using ADD and total body decomposition scores (Megyesi et al., 2005 [1]), the Drake Field data produced estimates of PMI more closely mirroring those of the research site than did Owl Creek. This demonstrates that instead of automatically choosing the nearest NWS station, care must be taken when choosing an NWS station for retroactively gathering temperature data for application of PMI estimation techniques using accumulated degree days to ensure the station adequately reflects temperature conditions at the recovery site. PMID- 20303686 TI - Risk factors for recurrence of small hepatocellular carcinoma after long-term follow-up of percutaneous radiofrequency ablation. AB - Radiofrequency ablation (RFA) as a local therapy for liver cancer is widely used. The study is to evaluate the therapeutic efficacy of RFA on hepatocellular carcinoma (HCC) and identify the risk factors for recurrence. Clinical records of 124 patients with 135 small HCC with percutaneous RFA as a first-line treatment modality were evaluated in Liver Cancer Institute, Zhongshan Hospital from October 2001 to December 2006. With a median follow-up period of 46 months after RFA therapy, the 1-, 2-, 3-, 4-, and 5-year cumulative survival rates and disease free survival rates were 91, 70, 61, 48 and 40% and 64, 44, 31, 24 and 24%, respectively. The total recurrence and metastasis rates were 50 and 6.5%, respectively. Independent risk factors for recurrence after RFA included tumor with diameter more than 3 cm, located near the intrahepatic blood vessels, subcapsular locations and PT prolonged more than 3s. Severe complications occurred in 2 cases (1.6%), including biliary tract hemorrhage and subphrenic effusion. RFA appears to be a safe and effective treatment for HCC. It will benefit the efficacy of RFA therapy if those risk factors are considered during the clinical practice. PMID- 20303685 TI - Recommendations for bone and joint prosthetic device infections in clinical practice (prosthesis, implants, osteosynthesis). Societe de Pathologie Infectieuse de Langue Francaise. PMID- 20303687 TI - Breast surgical specimen radiographs: how reliable are they? AB - Radiography of the excised surgical specimen following wire guided localisation of impalpable breast lesions is standard surgical practice. The aims of the study were to establish the reliability of the breast specimen radiograph (SR) in determining lesion excision and to determine whether the radiographic margin correlated with the histological margin. The clinical, imaging, SR and pathological details of 106 patients with a pre-operative diagnosis of breast cancer were retrospectively reviewed. The reliability of orientation was estimated and the appearance and distance from the mammographic abnormality to each radial margin were measured and correlated with surgical histological findings. The overall accuracy of the specimen radiograph in determining whether the mammographic lesion was present was 99%. The SR could be orientated "very reliably" or "reliably" in 80% of patients however in only 48% of patients did the closest margin on the SR correspond with the same nearest margin at final histology. A maximum measurement of 11 mm or more from the lesion to the specimen edge was associated with a 77% likelihood of having a clear final histological margin (taken as 5mm or more) and if <11 mm a 58% chance of having involved final histological margins. There was however a wide overlap in the results with patients having an apparently wide SR margin but histologically involved margins and vice versa. The SR is reliable at determining whether the target lesion has been removed. The correlation of SR margin orientation and measurement with final histological measurement is however far less reliable. PMID- 20303688 TI - Arsenic-resistant bacteria associated with roots of the wild Cirsium arvense (L.) plant from an arsenic polluted soil, and screening of potential plant growth promoting characteristics. AB - A rhizobacterial community, associated with the roots of wild thistle Cirsium arvense (L.) growing in an arsenic polluted soil, was studied by fluorescence in situ hybridization (FISH) analysis in conjunction with cultivation-based methods. In the bulk, rhizosphere, and rhizoplane fractions of the soil, the qualitative picture obtained by FISH analysis of the main phylogenetic bacterial groups was similar and was predominantly comprised of Alphaproteobacteria, Betaproteobacteria, and Gammaproteobacteria. The arsenic-resistant isolates belonged to 13 genera, the most abundant being those of Bacillus, Achromobacter, Brevundimonas, Microbacterium, and Ochrobactrum. Most bacteria grew in the presence of high arsenic concentrations (over 100mM arsenate and 10mM arsenite). Most strains possessed the ArsC, ArsB and ACR3 genes homologous to arsenate reductase and to the two classes of arsenite efflux pumps, respectively, peculiar to the ars operon of the arsenic detoxification system. ArsB and ACR3 were present simultaneously in highly resistant strains. An inconsistency between 16S rRNA phylogenetic affiliations and the arsenate reductase sequences of the strains was observed, indicating possible horizontal transfer of arsenic resistance genes in the soil bacterial community. Several isolates were able to reduce arsenate and to oxidise arsenite. In particular, Ancylobacter dichloromethanicum strain As3-1b possessed both characteristics, and arsenite oxidation occurred in the strain also under chemoautotrophic conditions. Some rhizobacteria produced siderophores, indole acetic acid and 1-amino-cyclopropane 1-carboxylic acid deaminase, thus possessing potential plant growth-promoting traits. PMID- 20303689 TI - Development and validation of a GC/IT-MS method for simultaneous quantitation of para and meta-synephrine in biological samples. AB - After the FDA's ban of ephedrine-containing supplements, Citrus aurantium appeared as an alternative to ephedra in herbal weight loss products. Synephrine, the most abundant active component of C. aurantium, exists in three different structural or positional isomeric forms (ortho-o-, meta-m-, and para-p-). Dietary supplements contain m- and p-synephrine, both alpha-adrenergic agonists,while the m-isoform is the most potent at alpha(1)-adrenoreceptors. In spite of the pharmacokinetic and toxicological interest in the study of these compounds, adequate methods for their quantification in biological samples are yet to be developed. Thus, in the present study, a sensitive gas chromatography-ion trap mass spectrometry (GC/IT-MS) method was developed and validated for the simultaneous quantitation of m- and p-synephrine in a cellular matrix after solid phase extraction (SPE). The validation of the method was performed through the evaluation of the following parameters: selectivity, linearity, specificity, precision, accuracy, limit of detection, limit of quantification, and recovery. The method's applicability was studied in two different biological matrices by evaluating p- and m-synephrine uptake in Caco-2 cells and also in freshly isolated cardiomyocytes from adult rat. The developed GC/IT-MS method was shown to be selective, accurate, precise, and valid for simultaneous determination of p and m-synephrine in biological samples. PMID- 20303690 TI - Quantitative determination of potent alpha-glucosidase inhibitors, salacinol and kotalanol, in Salacia species using liquid chromatography-mass spectrometry. AB - A practical HPLC-MS method for the quantitative determination of salacinol (1) and kotalanol (2), potent alpha-glucosidase inhibitors from Salacia species (Hippocrateaceae) as a specific remedy for diabetes in Ayurvedic system, was developed. The optimum conditions of separation and detection of these two constituents were achieved on a Asahipak NH2P-50 column (5 mcirom particle size, 2.0 mm i.d. x 150 mm) with a CH(3)CN-H(2)O mobile phase, associated with MS using electrospray ionization source. The overall recoveries of 1 (85.8-112.6%) and 2 (99.7-106.1%), and relative standard deviation values of intra- and inter-day precision were lower than 6.8 and 8.5%, respectively. The detection (S/N=3) and quantitation limits (S/N=10) were established to be 0.015 and 0.050 ng for 1, and 0.030 and 0.10 ng for 2, respectively. The correlation coefficients of all the calibration curves showed good linearity within test ranges. The extraction process was also optimized as 2 h immersion in water under reflux. The method was applied to evaluate extracts of three kinds of Salacia species, i.e. S. reticulata, S. oblonga, and S. chinensis, and those of four different parts, i.e. roots, stems, leaves and fruits of the same material, revealing that the extract from the roots of S. reticulata had the highest contents of these compounds. The results indicated that the assay was reproducible and precise and could be readily utilized for the evaluation of Salacia species. PMID- 20303691 TI - Physician practice patterns of obesity diagnosis and weight-related counseling. AB - METHODS: we analyzed cross-sectional clinical encounter data. Obese adults were obtained from the 2005 National Ambulatory Medical Care Survey (N=2458). RESULTS: a third of obese adults received an obesity diagnosis (28.9%) and approximately a fifth received counseling for weight reduction (17.6%), diet (25.2%), or exercise (20.5%). Women (OR=1.54; 95% CI: 1.14, 2.09), young adults ages 18-29 (OR=2.61; 95% CI: 1.37, 4.97), and severely/morbidly obese individuals (class II: OR 2.08; 95% CI: 1.53, 2.83; class III: OR 4.36; 95% CI: 3.09, 6.16) were significantly more likely to receive an obesity diagnosis. One of the biggest predictors of weight-related counseling was an obesity diagnosis (weight reduction: OR=5.72; 95% CI: 4.01, 8.17; diet: OR=2.89; 95% CI: 2.05, 4.06; exercise: OR=2.54; 95% CI: 1.67, 3.85). Other predictors of weight-related counseling included seeing a cardiologist/other internal medicine specialist, a preventive visit, or spending more time with the doctor (p<0.05). CONCLUSIONS: most obese patients do not receive an obesity diagnosis or weight-related counseling. PRACTICE IMPLICATIONS: preventive visits may provide a key opportunity for obese patients to receive weight-related counseling from their physician. PMID- 20303692 TI - Primary suture-anastomosis of the Viabahn endoprosthesis to a native artery. AB - We describe the case of a ruptured woven polyester common femoral-to-popliteal artery bypass graft, in which the lack of a suitable proximal landing zone precluded a totally endovascular approach to revascularization. The patient was treated with Viabahn endoprostheses (W. L. Gore & Associates, Flagstaff, Ariz), with the proximal end of the proximal Viabahn emerging from a graft arteriotomy and sutured directly end-to-side to the native common femoral artery. We believe this is the first reported case of a sutured anastomosis of the Viabahn endoprosthesis to a native vessel. The surgical technique is illustrated, and potential indications are discussed. PMID- 20303693 TI - Treatment of complex coarctation and coarctation with cardiac lesions using extra anatomic aortic bypass. AB - BACKGROUND: Coarctation of the aorta with cardiac lesions or complex coarctation is a formidable challenge for cardiac surgeons. Extra-anatomic bypass allows simultaneous intracardiac repair or an alternative approach for patients with complex coarctation. METHODS: Between July 1997 and March 2008, 43 patients with coarctation of the aorta underwent extra-anatomic bypass grafting, including 10 ascending-to-descending aorta bypasses and 33 ascending aorta-to-infrarenal abdominal aorta bypasses. Forty patients had additional cardiovascular disorders and concomitant procedures performed including aortic valve replacement, mitral valve replacement, coronary artery bypass grafting, closure of ventricular septal defect and patent ductus arteriosus, ascending aorta repair, and the Bentall procedure. The other three patients had complex coarctation of the aorta, including a long-segment coarctation in two cases, and descending aortic aneurysm in one. RESULTS: Two patients died perioperatively: one due to air embolism during the cardiopulmonary bypass; one due to septic shock. There were no late deaths. Complications included laparotomy for mechanical ileus in one and re exploration for bleeding in one case. There were no strokes or paraplegia and no grafted-related complication during follow-up period. Systolic blood pressure dropped from 160 +/- 27 mm Hg before surgery to 114 +/- 16 mm Hg postoperatively. Only two patients with mild hypertension postoperatively needed oral medicine. CONCLUSIONS: Extra-anatomic aortic bypass via median sternotomy or median sternotomy-laparotomy can be performed with low morbidity and mortality. It is a preferable single-stage approach for patients with concomitant complex coarctation and cardiovascular disorders. PMID- 20303694 TI - Open surgery remains a valid option for the treatment of recurrent carotid stenosis. AB - OBJECTIVE: The choice between open surgery (OS) and transluminal carotid angioplasty with stenting (CAS) for the treatment of primary carotid stenosis remains controversial. However, CAS is considered a valid option for selected cases, such as recurrent carotid stenosis (RCS). Tertiary RCS seems to be a concerning issue after CAS but few large reports focused on the durability of CAS and OS. We report our early and long-term results with OS for RCS. METHODS: From 1989 to 2006, perioperative data regarding 4245 consecutive surgical carotid reconstructions was prospectively collected. Patients whose indication was RCS were subjected to further analysis. Indications for surgery were symptomatic RCS >50% or asymptomatic RCS >80%. Freedom from neurologic event was defined as the absence of any ipsilateral symptom at any time after the procedure. Kaplan-Meier analysis was used to estimate freedom from reintervention, freedom from restenosis >50% and occlusion, freedom from neurologic event and survival. RESULTS: A total of 119 patients (2.8%) with RCS underwent OS. The average time from the primary OS was 59.4 +/- 54.5 months (range, 2-204). Forty-nine patients (41%) were symptomatic. In 103 patients (87%), the technique did not differ from a primary approach. Postoperative (<30 days) combined stroke and death rate was 3.3%. Cranial nerve injury occurred in 5 cases (4.2%). With a mean follow-up of 53 +/- 48 months (range, 1-204), 3 patients had an ipsilateral stroke (including one hemorrhagic stroke) and 7 were diagnosed with a tertiary RCS >50%. At 5 years, Kaplan-Meier estimates of freedom from reintervention, freedom from restenosis and occlusion, freedom from neurologic event, and survival were 99%, 91%, 89%, and 91%, respectively. CONCLUSION: OS for RCS is not a high-risk procedure and provides excellent long-term results, with low rates of tertiary RCS and reinterventions. The comparison between OS and CAS in this indication suffers from the absence of standardized follow-up paradigms after primary OS and the lack of prospective randomized trial comparing the two techniques. Despite these limitations in the available data, we conclude that OS should remain the first line therapy when treatment of RCS is indicated. PMID- 20303695 TI - Outcomes of the endovascular management of aortic arch aneurysm: implications for management of the left subclavian artery. AB - BACKGROUND: This study was conducted to define the outcomes of treating aortic aneurysms involving the arch vessels with a hybrid approach using extra-anatomic reconstruction and endovascular repair with nonfenestrated stents. METHODS: A single-center review was done of arch aneurysm endovascular repairs during an 8 year period. Data were collected for patient demographics and aneurysm pathology. Any revascularization procedures performed were analyzed to detect differences between groups and through fitting a logistic regression model. The outcome measures were postoperative death, stroke, and paraplegia. RESULTS: Between 2001 and 2009, 78 patients (65% men; mean age, 65 years) underwent endovascular repair of aortic arch aneurysms. Coverage of the left subclavian artery (LSA) was necessary in all patients to access an adequate proximal landing zone. An Ishimaru zone 0 proximal landing zone was present in 9 patients, 17 had zone 1, and 52 had zone 2. Fifty patients (64%) underwent elective endografting with an in-hospital mortality rate of 4%, and 28 patients (36%) underwent emergency procedures with a mortality rate of 14.3%. The LSA was revascularized in 31 elective (62%) and 4 emergency patients (14%). LSA revascularization was associated with significantly better outcomes for the combined measure of death, stroke, and paraplegia (odds ratio [OR], 15.6; 95% confidence interval [CI], 1.83 142; P = .012). Patients with an atherosclerotic aneurysm had worse outcomes than those with aortic dissection (OR, 5.52; 95% CI 1.26-24.4; P = .024), with dissections having preponderance toward emergency procedures (OR, 2.92; 95% CI, 1.12-7.58; P = .035). CONCLUSION: Aneurysms involving the aortic arch vessels can be effectively treated by staged endovascular-surgical hybrid procedures with good outcomes that can be further improved through prior revascularization of the LSA. PMID- 20303697 TI - [Classification of new medical students and their outcome at the National Ranking Examination]. PMID- 20303699 TI - Penile and scrotal skin necrosis after injection of crushed buprenorphine tablets. PMID- 20303700 TI - [Restless legs syndrome: a genetic disease?]. AB - Restless legs syndrome (RLS) is characterized by an unpleasant sensation in the lower limbs and an urge to move, occurring during periods of rest, in the evening and during the night and improved by movement. There are two different phenotypes of RLS: an early-onset form, starting before 36 years old with mostly a familial history, being mostly severe and highly genetically determined, with a high dependence to iron brain levels; a delayed-onset form, starting after 36 years old, mostly secondary, without familial history, with a rapid evolution in two or three years, and with frequent low ferritine serum levels. The primary form of RLS is associated with a familial history in 40 to 92 % of the patients. Monozygotic twins have a 54 to 83 % concordance rate for RLS phenotype. Linkage association studies have identified eight loci involved in the familial transmission of the disease. Genetic association studies have identified allelic variants responsible for a 50 % increased risk to develop RLS in the general population. Proteins coded by some implicated genes are involved in the development of spinal motor neurons and spinal dorsal horns, and in brain iron homeostasis. PMID- 20303703 TI - Thrombosis in acquired hyposplenism associated with Crohn disease. PMID- 20303704 TI - [Management of restless legs syndrome]. AB - The first step in the management of restless legs syndrome (RLS) is to identify, and if possible to treat any condition which might cause or worsen RLS, such as iron deficiency or some drug treatments. The patients suffering from RLS should be prompted to keep a healthy sleep schedule. Drug treatment should be restricted to patients with a clear clinical diagnosis, decided on an individual basis, when the clinical impact is serious. Four drug classes are central to the treatment of RLS: dopaminergic agents, some antiepileptics, opioids, and benzodiazepines. Dopaminergic agonists are the treatment of choice, especially when daily treatment is indicated, or if the symptoms are severe. Two dopaminergic agonists are licensed in France for the treatment of RLS: ropinirole (Adartrel) and pramipexole (Sifrol). After initiation of treatment, the patients should benefit from a regular follow-up in order to evaluate the efficacy of treatment and to identify possible side-effects. Special care should be given to the detection of augmentation, a phenomenon characterized by a paradoxical worsening of the symptoms with treatment. Some particular conditions, such as RLS comorbid with renal insufficiency, during pregnancy, and in the child are discussed. PMID- 20303706 TI - [Placenta accreta: Frequency, prenatal diagnosis and management]. AB - In the last 30 years, incidence of placenta accreta has dramatically increased to reach an alarming rate of more than one in 2500 deliveries. The rate of placenta accreta increased in conjunction with cesarean deliveries. 2D-ultrasonography is an useful tool to diagnose placenta accreta. The most reliable sign is the presence of abnormal placental lacunae. The lack of visualization of the echolucent area between the placenta and the myometrium with no other ultrasound finding has a poor sensitivity and positive predictive value. 3D power Doppler is useful to increase the diagnostic performance of 2D-ultrasonography. The presence of at least two ultrasound findings decreases the number of false-positive diagnosis and increases the performance of both 2D-ultrasonography and 3D power Doppler. Magnetic resonance imaging in cases with inconclusive ultrasound features optimizes diagnostic accuracy. In cases of prenatal diagnosis of placenta accreta, extirpative method should be to date abandoned. Advantages and disadvantages of both cesarean-hysterectomy and conservative treatment should be clearly explained to the patient and her partner, who have to be involved in the decision process. Currently, it seems to be reasonable to propose a cesarean hysterectomy to multiparous patients with no desire of future pregnancy. In young women who want the option of future pregnancy and who agree to close follow-up monitoring, conservative treatment should be preferred. When placenta accreta is diagnosed during the delivery, the two options remain possible only if attempts of removal of the placenta are stopped before the occurrence of a severe postpartum hemorrhage. In cases of placenta percreta with bladder involvement, conservative treatment may be the optimal management. PMID- 20303708 TI - Visual feedback and weight reduction of a grip strength dynamometer do not increase reliability in healthy children. AB - STUDY DESIGN: Test-retest reliability study on grip strength in children. INTRODUCTION: Measuring grip strength in children is difficult because of the weight and size of the instrument, brief attention span, and possible lack of task understanding. Therefore, adaptations to the measurement protocols to improve reliability would be very important for research and clinical evaluation. PURPOSE: In this study, we compared the reliability of a grip strength dynamometer (Lode dynamometer, Lode BV, Groningen, The Netherlands) using three different protocols. METHODS: Test-retest reliability of the American Society of Hand Therapists protocol in 104 healthy children (4-12 years) was compared with the reliability in 63 healthy children of a visual feedback protocol and a suspension protocol reducing weight of the instrument. RESULTS: For the total group, intraclass correlation coefficients for the dominant and nondominant hands were 0.95-0.97 for all protocols, indicating that all three protocols were reliable. CONCLUSION: No statistically significant difference was found among the reliability of the different protocols, but the suspension protocol produced small but significantly higher force levels. LEVEL OF EVIDENCE: Not applicable. PMID- 20303709 TI - A prospective global measure, the Punum Ladder, provides more valid assessments of quality of life than a retrospective transition measure. AB - OBJECTIVES: We assessed the reliability and validity of two measures of change, one retrospective (the Global Rating of Change Scale [GRCS]) and one prospective (the Punum Ladder), and the relative utility of the two methods of assessing change and establishing the minimal important difference (MID) of the Cough Quality of Life Questionnaire (CQLQ), a reliable and valid cough-specific quality of-life (QoL) instrument. STUDY DESIGN AND SETTING: A prospective, longitudinal study assessing the change in cough-related QoL over 6 months in participants with chronic cough was carried out in a tertiary care cough clinic. Before seeing a physician, subjects completed eight Punum Ladders and the CQLQ. At 1 and 6 months, eight Punum Ladders, the CQLQ, and seven GRCSs were completed. Punum Ladders and GRCSs were psychometrically tested, and MIDs were calculated. RESULTS: Reliability and validity of GRCSs and Punum Ladders were acceptable. However, closer analysis of the relation between change scores and CQLQ pretest and posttest scores showed that the GRCS was only related to patient's present state, whereas the Punum Ladder was associated with both initial and present states. This compromises the validity of the GRCS. Crosstab comparisons revealed that GRCS ratings made more liberal estimates of change in the CQLQ than the Punum Ladder; this is reflected in their respective MIDs (10.58+/-10.63 vs. 21.89+/-15.38). CONCLUSION: The prospective Punum Ladder is likely to be more useful, because it reflects the actual change in QoL over time in a less biased and more accurate way than the retrospective GRCS. PMID- 20303710 TI - Community controls were preferred to hospital controls in a case-control study where the cases are derived from the hospital. AB - OBJECTIVE: Cases and controls should be chosen from the same base population to reduce selection bias in case-control studies. For hospital cases, we examined how inferences drawn from a case-control study can differ by choice of hospital- vs. community-based controls. STUDY DESIGN AND SETTINGS: We used data from a case control study that assessed risk factors for community-acquired pneumonia (CAP) hospitalization in Hamilton, Ontario, and Edmonton, Alberta, Canada. Multiple logistic regression was used to identify risk factors for hospitalization with CAP by simultaneously fitting two regression models. Binary logistic regression was used to directly compare the distributions of such risk factors in hospital and community controls. RESULTS: The use of hospital controls did not identify any additional risk factors for hospitalization that were not identified using community-based controls. Distributions of potential risk factors differed significantly between hospital and community control groups. We observed weaker or null estimates of associations with hospital controls compared with community controls. CONCLUSION: Inferences differed depending on the source of control groups. The use of hospital controls tended to produce no or weaker associations than those using community controls. If a high response rate can be attained, the best choice of controls may be from the community. PMID- 20303711 TI - The likelihood of participation in clinical trials can be measured: the Clinical Research Involvement Scales. AB - OBJECTIVE: We developed the Clinical Research Involvement Scales (CRIS) to assess the willingness to participate in a clinical trial. STUDY DESIGN AND SETTING: Diverse populations (N=919) aged 18 years or older from Atlanta, Georgia, were included in comprehensive testing of the 41-item CRIS instrument. The formative phase focused on item content for the new measures (n=54). Questionnaires from potential vaccine trial participants (n=865), collected at multiple time points, resulted in the evaluation of scale reliability and validity (i.e., attitudes, behavioral and normative beliefs, perceived social support for clinical research participation, social norm compliance, perceptions of the clinical research organization, and perceived relevance of the research endeavor). RESULTS: Qualitative testing revealed adequate comprehension and content validity of the initial item set. The subjective norms domain (n=3) initially exhibited poor internal consistency in pilot testing (Cronbach's alpha=0.525); yet, rewording of the items resulted in consistently stable measurement improvement (Cronbach's alpha=0.850). Each of the CRIS subscales demonstrated extremely high reliability, ranging from 0.734 to 0.918. Confirmatory factor analysis verified item-factor relationships and determined construct and convergent validity (root mean square error of approximation=0.068; comparative fit index=0.835). CONCLUSIONS: CRIS is a reliable instrument for measuring community attitudes toward participation in biomedical research studies. Results of this study support the use of these scales to recruit diverse populations to clinical trials. PMID- 20303713 TI - Dysfunctional gamma-band activity during face structural processing in schizophrenia patients. AB - This study investigated gamma-band activity (GBA) and its phase synchrony in schizophrenia patients viewing human faces. Twenty-five schizophrenia patients were compared with 25 normal controls. Event-related potentials were recorded from all participants while they were viewing emotionally neutral faces. The spectral power and phase synchrony in the frequency band from 30 to 55 Hz were analyzed in midline electrodes (FCz, Cz, CPz, Pz, and POz). Three windows of interest, which showed discernable GBA differences between schizophrenia patients and normal controls, were selected by visual inspection: 0-100 ms (30-33 Hz), 250 300 ms (34-38 Hz), and 700-800 ms (40-45 Hz). And the phase synchrony of gamma band was analyzed. Repeated-measures ANOVA revealed that the GBA was lower in schizophrenia patients than in normal controls. Also there were significant location and time differences in GBA. GBA was significantly lower in the schizophrenia patients than in the normal controls at around 700-800 ms at the FCz electrode. The frontal (FCz) and central (Cz) GBA were significantly correlated with the number of hospitalization, and the negative symptoms of schizophrenia, respectively. The phase synchronization was significantly lower at 200-300 ms in the schizophrenia patients than in the normal controls. These findings suggest that the schizophrenia patients have impaired GBA and gamma-band synchronization during face perception. Furthermore, our results also suggest that the decreased GBA observed at the midline cortex of schizophrenia patients is closely related to their negative symptoms and disease progress. PMID- 20303712 TI - Tg.2098 is a major human thyroglobulin T-cell epitope. AB - An HLA-DR variant containing Arginine at position 74 of the DRbeta1 chain confers a strong genetic susceptibility to autoimmune thyroid diseases (AITD), Graves' disease (GD) and Hashimoto's thyroiditis (HT), while Glutamine at position DRbeta1-74 is protective. We hypothesized that the DRbeta1-Arg74 variant is able to present pathogenic thyroglobulin (Tg) peptides to T-cells more efficiently, thereby triggering thyroid autoimmunity. Indeed, we have previously identified 4 human Tg (hTg) peptides that bind specifically to DRbeta1-Arg74 with much weaker binding to the protective variant DRbeta1-Gln74. The aim of our study was to examine in vivo whether an hTg peptide that binds strongly and specifically to DRbeta1-Arg74 is capable of stimulating T-cells during the induction of thyroiditis in a "humanized" mouse expressing human DR3, and in patients positive for Tg antibodies. Sequencing of exon 2 of the DR transgene in the DR3 mice, null for endogenous MHC II molecules, confirmed that they expressed the disease associated DRbeta1-Arg74 variant, thus making them an ideal in vivo model to test the presentation of hTg peptides by DRbeta1-Arg74 HLA-DR. Induction of EAT in the DR3 mice lead to T-cell stimulation and proliferation to Tg.2098, a strong and specific DRbeta1-Arg74 binder, while a non-binding control peptide, Tg.2766 did not induce this response. Moreover, Tg.2098 stimulated T-cells from 4 individuals who were positive for thyroglobulin antibodies, demonstrating that Tg.2098 is an immunogenic peptide capable of being presented in vivo and activating T-cells in EAT and AITD. Energetic analysis of the complex formed by Tg.2098 and DRbeta Arg74 has shown that the origin of the affinity was determined by residues 1, 7 and 9 in the peptide, while the selectivity of the peptide for the MHC was determined by the Asp in position 4. The disease-protective substitution R74Q, leads to reduction in affinity due to changes in local interaction with D4 as well as non-local interaction with other residues. The electrostatic potential on the surface of the DRbeta-Arg74-Tg.2098 complex has a unique signature which may be recognized by T-cell receptors leading to autoimmune thyroiditis. Taken together these findings suggest that Tg.2098, a strong and specific binder to the disease-associated HLA-DRbeta-Arg74, is a major human T-cell epitope and participant in the pathoetiology of AITD. PMID- 20303714 TI - Substance use disorder comorbidity with schizophrenia in families of Mexican and Central American ancestry. AB - OBJECTIVES: The aims of this study were to estimate the frequency and course of substances use disorders in Latino patients with schizophrenia and to ascertain risk factors associated with substance use disorders in this population. METHOD: We studied 518 subjects with schizophrenia recruited for a genetic study from the Southwest United States, Mexico, and Central America (Costa Rica and Guatemala). Subjects were assessed using structured interviews and a best estimate consensus process. Logistic regression, chi(2), t test, Fisher's exact test, and Yates' correction, as appropriate, were performed to assess the sociodemographic variables associated with dual diagnosis. We defined substance use disorder as either alcohol or substance abuse or dependence. RESULTS: Out of 518 patients with schizophrenia, 121 (23.4%) had substance use disorders. Comorbid substance use disorders were associated with male gender, residence in the United States, immigration of Mexican men to the United States, history of depressive syndrome or episode, and being unemployed. The most frequent substance use disorder was alcohol abuse/dependence, followed by marijuana abuse/dependence, and solvent abuse/dependence. CONCLUSION: This study provides data suggesting that depressive episode or syndrome, unemployment, male gender, and immigration of Mexican men to the United States were factors associated with substance use disorder comorbidity in schizophrenia. Binary logistic regression showed that country of residence was associated with substance use disorder in schizophrenic patients. The percentage of subjects with comorbid substance use disorders was higher in the Latinos living in the United States compared with subjects living in Central America and Mexico. PMID- 20303715 TI - Subjective rating of working memory is associated with frontal lobe volume in schizophrenia. AB - BACKGROUND: Patients with schizophrenia commonly show deficits in working memory on objective neuropsychological measures, and brain imaging studies have documented neural abnormalities during performance of working memory tasks. It remains unclear to what extent such patients are able to accurately gauge the integrity of their working memory in their daily lives. AIMS: We evaluated the relationship between subjective rating of working memory integrity in daily life and volumes of the frontal, temporal, and parietal lobes in patients with schizophrenia. METHODS: Participants included 29 patients with schizophrenia and 26 healthy comparison subjects. Participants completed a structural magnetic resonance imaging (MRI) scan, the Self Report form of the Behavioral Rating Inventory of Executive Function - Adult version (BRIEF-A), and Digit Span Backwards as an objective measure of working memory. Lobar volumes were obtained using an automated processing package and adjusted for total intracranial volume. RESULTS: The patient group reported worse working memory in daily life, and performed worse on Digit Span Backwards, than the comparison group. Within the patient group, poorer working memory in daily life was associated with smaller left and right frontal lobe volumes. Shorter backwards digit span was associated with smaller left frontal and left and right temporal lobe volumes. CONCLUSIONS: The significant relationship between frontal lobe volumes and subjective working memory in daily life provides some support for the validity of self report measures of cognitive functioning in patients with schizophrenia, and provides further evidence for a contribution of frontal lobe abnormality to executive dysfunction in the illness. PMID- 20303716 TI - Comparative efficacy of novobiocin and amoxicillin in experimental sepsis caused by beta-lactam-susceptible and highly resistant pneumococci. AB - Therapeutic alternatives are needed against infections caused by highly multidrug resistant Streptococcus pneumoniae. Novobiocin, an old antibiotic, was tested in vitro and in a murine sepsis model against one amoxicillin-susceptible and three amoxicillin-resistant strains [minimum inhibitory concentrations (MICs) 8-64 mg/L]. Novobiocin MICs for all strains were 0.25-0.5 mg/L. In sepsis, novobiocin and amoxicillin were evaluated at 25, 50, 100 and 200 mg/kg given at 1, 5, 24 and 48 h post bacterial challenge. The most effective regimens in animals infected with the amoxicillin-susceptible strain were 200 mg/kg novobiocin and 25 mg/kg amoxicillin, achieving 100% survival and undetectable organisms in the peritoneum. Among mice infected with amoxicillin-resistant S. pneumoniae, 200 mg/kg novobiocin gave the highest protection (90-100% survivors), followed by 200mg/kg amoxicillin (60-100%), 100 mg/kg novobiocin (50-87.5%) and 50 mg/kg amoxicillin (14.3-25%). The killing effect of antibiotics in the peritoneum (mean Deltalog(10) colony-forming units/mL between treated and control mice) was as follows: 200 mg/kg novobiocin (-6.6)>200 mg/kg amoxicillin (-5.6)>100 mg/kg novobiocin (-3.7) > 50 mg/kg amoxicillin (-0.7). Total plasma and ultrafiltrate pharmacokinetics of novobiocin (200 mg/kg, single dose) in non-infected mice showed, respectively, half-lives of 151 min and 215 min, area under the concentration-time curves (AUCs) of 945.0 mgh/L and 136.6 mgh/L and maximal concentrations of 147 mg/L and 18 mg/L. Novobiocin may be a promising agent for therapy of highly beta-lactam-resistant pneumococcal infections. PMID- 20303717 TI - Morphological and molecular characterization of Aspidisca hongkongensis spec. nov. (Ciliophora, Euplotida) from the South China Sea. AB - The morphology and infraciliature of a new ciliate, Aspidisca hongkongensis spec. nov., a large marine form isolated from the coastal waters near Hong Kong, were investigated. It differs from the congeners by the combination of cell size (about 90 x 60 microm in vivo), 9-11 conspicuous dorsal ridges, one fine and seven strong frontoventral cirri, six membranelles in anterior portion of adoral zone, and 17-23 membranelles in posterior portion of adoral zone. The comparison with similar congeners clearly supports the distinction of this new species based on morphological and small subunit (SSU) rRNA gene sequence studies. The SSU rRNA gene sequence similarity within the genus is about 75.3-92.1% which indicates that this is a distinct form. Phylogenetic trees based on SSU rRNA gene information show that A. hongkongensis groups with A. leptaspis. PMID- 20303718 TI - Adjuvant radiotherapy with 50 Gy after limb-sparing surgery for soft-tissue sarcoma--West of Scotland experience. PMID- 20303719 TI - Sub-clinical organ damage in hypertension and obesity. AB - BACKGROUND: The development of sub-clinical organ damage precedes and predicts the occurrence of cardiovascular (CV) events in hypertensive as well as in obese patients. AIM AND METHODS: We investigated the prevalence and clinical correlates of organ damage (OD), namely carotid atherosclerosis (US scan) and urine albumin to creatinine ratio (three non-consecutive first morning samples) in a group of 164 obese patients and in an age- and gender-matched group of non-obese hypertensive patients. RESULTS: There was a significantly greater prevalence and severity of OD in obese patients as compared to non-obese hypertensive patients. In particular obese patients more frequently had microalbuminuria (16 vs 7%, chi(2) 5.8, P=0.0157) and carotid abnormalities (53 vs 10%, chi(2) 69.5, P<0.0001) as well as higher urinary albumin excretion rate (-0.05 +/- 0.52 vs 0.28 +/- 0.43log ACR, P<0.0001) and carotid intima-media thickness (0.955 +/- 0.224 vs 0.681 +/- 0.171, <0.0001). Notably, the coexistence of hypertension and obesity did not entail a greater prevalence and severity of OD. Moreover, after adjusting for potentially confounding factors including blood pressure levels, diagnosis of diabetes, and lipid profile, morbidly obese patients showed a 5 fold, and 22-fold higher risk of having microalbuminuria, and carotid atherosclerosis, respectively. CONCLUSIONS: Sub-clinical OD is highly prevalent in obese patients, even in the absence of high blood pressure. Hypertension and obesity seem to exert an independent, possibly non-additive role on the occurrence of organ damage. PMID- 20303720 TI - Olive oil and health: summary of the II international conference on olive oil and health consensus report, Jaen and Cordoba (Spain) 2008. AB - Olive oil (OO) is the most representative food of the traditional Mediterranean Diet (MedDiet). Increasing evidence suggests that monounsaturated fatty acids (MUFA) as a nutrient, OO as a food, and the MedDiet as a food pattern are associated with a decreased risk of cardiovascular disease, obesity, metabolic syndrome, type 2 diabetes and hypertension. A MedDiet rich in OO and OO per se has been shown to improve cardiovascular risk factors, such as lipid profiles, blood pressure, postprandial hyperlipidemia, endothelial dysfunction, oxidative stress, and antithrombotic profiles. Some of these beneficial effects can be attributed to the OO minor components. Therefore, the definition of the MedDiet should include OO. Phenolic compounds in OO have shown antioxidant and anti inflammatory properties, prevent lipoperoxidation, induce favorable changes of lipid profile, improve endothelial function, and disclose antithrombotic properties. Observational studies from Mediterranean cohorts have suggested that dietary MUFA may be protective against age-related cognitive decline and Alzheimer's disease. Recent studies consistently support the concept that the OO rich MedDiet is compatible with healthier aging and increased longevity. In countries where the population adheres to the MedDiet, such as Spain, Greece and Italy, and OO is the principal source of fat, rates of cancer incidence are lower than in northern European countries. Experimental and human cellular studies have provided new evidence on the potential protective effect of OO on cancer. Furthermore, results of case-control and cohort studies suggest that MUFA intake including OO is associated with a reduction in cancer risk (mainly breast, colorectal and prostate cancers). PMID- 20303721 TI - Cardioprotective effect of Sida rhomboidea. Roxb extract against isoproterenol induced myocardial necrosis in rats. AB - The present study investigates cardioprotective effect of Sida rhomboidea. Roxb (SR) extract on heart weight, plasma lipid profile, plasma marker enzymes, lipid peroxidation, endogenous enzymatic and non-enzymatic antioxidants and membrane bound ATPases against isoproterenol (IP) induced myocardial necrosis (MN) in rats. Rats treated with IP (85 mg/kg, s.c.) recorded significant (p<0.05) increment in heart weight, plasma lipid profile, plasma marker enzymes of cardiac damage, cardiac lipid peroxidation (LPO) and activity levels of Ca(+2) ATPase whereas there was significant (p<0.05) decrease in plasma HDL, cardiac endogenous enzymatic and non-enzymatic antioxidants, Na(+)-K(+) ATPase and Mg(+2) ATPase. Pre-treatment with SR extract (400 mg/kg per day, p.o.) for 30 consecutive days followed by IP injections on days 29th and 30th, showed significant (p<0.05) decrease in heart weight, plasma lipid profile, plasma marker enzymes of cardiac damage, cardiac lipid peroxidation, Ca(+2) ATPase and significant increase in plasma HDL, cardiac endogenous enzymatic and non-enzymatic antioxidants, Na(+) K(+) ATPase and Mg(+2) ATPase compared to IP treated group. Hence, this study is the first scientific report on cardioprotective effect of SR against IP induced MN in rats. PMID- 20303722 TI - Current Opinion in Immunology. Editorial overview. PMID- 20303723 TI - Alpha-1 antitrypsin deficiency. AB - OBJECTIVE: To review the topic of alpha-1 antitrypsin (AAT) deficiency. METHOD: Narrative literature review. RESULTS: Much work has been carried out on this condition with many questions being answered but still further questions remain. DISCUSSION AND CONCLUSIONS: AAT deficiency is an autosomal co-dominantly inherited disease which affects the lungs and liver predominantly. The clinical manifestations, prevalence, genetics, molecular pathophysiology, screening and treatment recommendations are summarised in this review. PMID- 20303724 TI - Do obstructive and restrictive lung diseases share common underlying mechanisms of breathlessness? AB - This review tries to answer two main questions: (i) What are the neurophysiological underpinnings of the most commonly selected cluster descriptors which define the qualitative dimension of dyspnea in patients? (ii) How do mechanical constraints affect dyspnea? (iii) Do obstructive and restrictive lung diseases share some common underlying mechanisms? Qualitative dimensions of dyspnea, which allude to increased respiratory work/effort breathing, reflect a harmonious coupling between increased respiratory motor output and lung volume displacement in healthy subjects. Descriptors that allude to unsatisfied inspiration are the dominant qualitative descriptors in patients with a variety of respiratory diseases. It is possible that sensory feedback from a multitude of mechanoreceptors throughout the respiratory system (in the muscle, chest wall, airways and lung parenchyma) collectively convey information to the consciousness that volume/flow or chest wall displacement is inadequate for the prevailing respiratory drive. The data would lend support to the idea that: (i) an altered afferent proprioceptive peripheral feedback signals that ventilatory response is inadequate to the prevailing motor drive, reflecting neuromechanical uncoupling (NMU), (ii) mechanical constraints on volume expansion (dynamic restriction) play a pivotal role in dyspnea causation in patients with a variety of either obstructive or restrictive respiratory disorders, and (iii) all of the physiological adaptations that optimize neuromechanical coupling in obstructive and restrictive disorders are seriously disrupted so that an NMU underpins cluster descriptors of dyspnea which are similar in obstructed and in restricted patients. PMID- 20303725 TI - Trends in bronchiectasis mortality in England and Wales. AB - BACKGROUND: To provide information on the burden of bronchiectasis in England and Wales, we have examined trends in mortality using death certificate data available from the Office of National Statistics. METHODS: We extracted data on deaths due to non-cystic fibrosis bronchiectasis for 2001-2007 inclusive and stratified deaths by sex and age group. We used Poisson regression to compare mortality rates. RESULTS: Between 2001 and 2007, 5745 bronchiectasis related deaths were registered in England and Wales. When standardized to the 2007 population, this showed a rise in absolute numbers from 797 (2001) to 908 (2007). Statistical analyses suggested that the mortality rate is currently increasing at 3%/year (p < 0.001). Mortality rates were similar between men and women but there was a strong statistical interaction between age group and year (p < 0.001) Rates were increasing in the two oldest age groups but falling in the three youngest groups. DISCUSSION: Currently just under 1000 people die from bronchiectasis each year in England and Wales. We found the number of deaths to be increasing at 3% per year. Although overall mortality was increasing, rates were increasing in older groups but falling in the younger groups. These mortality rates may underestimate the burden of disease from bronchiectasis as lack of knowledge about the disease may lead to underreporting. These are also mortality rather than incidence data and may reflect improvements in treatment. Bronchiectasis therefore remains a significant concern. Clinical provision will potentially need to increase in order to care for this patient group. PMID- 20303727 TI - Involvement of nucleophosmin/B23 in the cellular response to curcumin. AB - Nucleophosmin (NPM/B23) is a nucleolar phosphoprotein involved in cellular response to many different stimuli. Herein, we studied the molecular mechanism of NPM/B23 induction by curcumin, a natural AP-1 inhibitor with antitumor properties. Exposure to 5-30 MUM curcumin significantly and dose-dependently increased the level of NPM/B23 in non-transformed NIH 3T3 cells but not HeLa cells and F9 cells. Besides, the transformed F9 and HeLa cells are more sensitive to curcumin-induced cell death and growth inhibition than NIH 3T3 cells. Overexpression of c-Jun, but not c-Fos, decreased ~40% of NPM/B23 and enhanced the sensitivity of NIH 3T3 cells to 30 MUM curcumin. Furthermore, down-regulation of NPM/B23 by transfection with NPM/B23 antisense plasmid enhanced the sensitivity to curcumin-induced cell death and growth inhibition. These results indicated that NPM/B23 expression regulates cellular sensitivity to curcumin. Besides, NPM/B23 knockdown may facilitate as a novel strategy to promote the sensitivity of cancer cells to curcumin. PMID- 20303726 TI - Down the rabbit hole of centromere assembly and dynamics. AB - The centromere is perhaps the most iconic feature on a eukaryotic chromosome. An amateur enthusiast equipped with a light microscope can easily identify the center of each metacentric chromosome, marking the spot responsible for accurate genome segregation. This review will highlight findings that provide novel insights into how centromeres are assembled and disassembled, the role centromeric proteins play in repair, epigenetic features uniquely found at the centromere, and the three dimensional organization of centromeres caught in the act of mitosis. These advances have unveiled a veritable wonderland of non canonical features that drive centromere function. PMID- 20303728 TI - Integrated hepatic transcriptome and proteome analysis of mice with high-fat diet induced nonalcoholic fatty liver disease. AB - Nonalcoholic fatty liver disease (NAFLD) is the most common form of liver disease in the US and refers to a wide spectrum of liver damage, including simple steatosis, steatohepatitis, fibrosis and cirrhosis. The goal of the present study was to achieve a more detailed understanding of the molecular changes in response to high fat-induced liver steatosis through the identification of a differentially expressed liver transcriptome and proteome. Male C57/BL6 mice fed a high-fat lard diet for 8 weeks developed visceral obesity and hepatic steatosis characterized by significantly increased liver and plasma free fatty acid and triglyceride levels and plasma alanine aminotransferase activities. Transcriptome analysis demonstrated that, compared to the control diet (CD), high-fat diet changed the expression of 309 genes (132 up- and 177 down-regulated; by a twofold change and more, P<.05). Multiple genes encoding proteins involved in lipogenesis were down-regulated, whereas genes involved in fatty acid oxidation were up regulated. Proteomic analysis revealed 12 proteins which were differentially expressed. Of these, glutathione S-transferases mu1 and pi1 and selenium-binding protein 2 were decreased at both the gene and protein levels. This is the first study to perform a parallel transcriptomic and proteomic analysis of diet-induced hepatic steatosis. Several key pathways involving xenobiotic and lipid metabolism, the inflammatory response and cell-cycle control were identified. These pathways provide targets for future mechanistic and therapeutic studies as related to the development and prevention of NAFLD. PMID- 20303729 TI - Emulsified lipids increase endotoxemia: possible role in early postprandial low grade inflammation. AB - Low-grade inflammation is a risk factor for the onset of atherosclerosis. Little is known about the involvement of endotoxin absorption from the gut during the digestion of lipids. In the present study, we first investigated in humans the impact of a mixed meal containing dispersed lipids on postprandial endotoxemia and inflammation. We then investigated the effect of (i) oil emulsification in vivo in rats and (ii) fatty acid amounts in vitro using Caco-2 cells on postprandial endotoxemia. In humans, postprandial endotoxemia increased early after the meal. Moreover, we evidenced that the endotoxin receptor sCD14 increased during digestion and that chylomicrons could contribute to absorbed endotoxin transport. This could explain the significant peak of inflammatory cytokine IL-6 that we observed 2 h after the mixed meal. Interestingly, in rats, the emulsion led to both higher endotoxemia and hypertriglyceridemia than oil and compared to a control saline load. In vitro, incubation of Caco-2 cells with increasing fatty acid concentrations enhanced epithelial absorption of endotoxin. To our knowledge, this is the first study evidencing in healthy humans that, following a mixed meal containing lipids, increased endotoxemia is associated with raised sCD14 and a peak of IL-6. On a repeated basis, this may thus be a triggering cascade for the onset of atherosclerosis. In this respect, optimizing both dietary fat amount and structure could be a possible strategy to limit such low-grade endotoxemia and inflammation by the control of postprandial lipemia. PMID- 20303730 TI - mRNA transcripts as molecular biomarkers in medicine and nutrition. AB - In medicine, mRNA transcripts are being developed as molecular biomarkers for the diagnosis and treatment of a number of diseases. These biomarkers offer early and more accurate prediction and diagnosis of disease and disease progression, and ability to identify individuals at risk. Use of microarrays also offers opportunity to identify orthogonal (uncorrelated) biomarkers not known to be linked with conventional biomarkers. Investigators are increasingly using blood as a surrogate tissue for biopsy and analysis; total RNA isolated from whole blood is predominantly from erythroid cells, and whole blood mRNA shares more than 80% of the transcriptome with major tissues. Thus blood mRNA biomarkers for individualized disease prediction and diagnosis are an exciting area in medicine; mRNA biomarkers in nutrition have potential application that parallels these opportunities. Assessment of selenium (Se) status and requirements is one area where tissue mRNA levels have been used successfully. Selenoprotein-H and selenoprotein-W as well as glutathione peroxidase-1 (Gpx1) mRNAs are highly down regulated in Se deficiency in rat liver, and the minimum dietary Se requirement is 0.06-0.07 microg Se/g based on these biomarkers, similar to requirements determined using conventional biomarkers. Blood Gpx1 mRNA can also be used to determine Se requirements in rats, showing that blood mRNA has potential for assessment of nutrient status. Future research is needed to develop mRNA biomarker panels for all nutrients that will discriminate between deficient, marginal, adequate and supernutritional individuals and populations, and differentiate between individuals who will benefit vs. be adversely affected by nutrient supplementation. PMID- 20303731 TI - Postnatal early overfeeding induces hypothalamic higher SOCS3 expression and lower STAT3 activity in adult rats. AB - Postnatal early overnutrition (EO) is a risk factor for future obesity and metabolic disorders. Rats raised in small litters (SLs) develop overweight, hyperphagia, hyperleptinemia, hyperinsulinemia and hypertension when adults. As obesity is related to hyperleptinemia, leptin resistance and metabolic syndrome, we aimed to investigate body composition, plasma hormone levels, glucose tolerance and the leptin signaling pathway in hypothalamus from early overfed animals at weaning and adulthood. To induce postnatal EO, we reduced litter size to three pups/litter (SL), and the groups with normal litter size (10 pups/litter) were used as control. Rats had free access to standard diet and water postweaning. Body weight and food intake were monitored daily, and offspring were killed at 21 (weaning) and 180 days old (adulthood). Postnatal EO group had higher body weight and total and visceral fat mass at both periods. Lean mass and serum high-density lipoprotein cholesterol (HDL-C) were higher at 21 days and lower at 180 days. Small litter rats presented higher levels of globulins at both periods, while albumin levels were higher at weaning and lower at adulthood. There was higher leptin, insulin and glucose serum concentrations at 21 days old, while no glucose intolerance was observed in adulthood. Leptin signaling pathway was unaffected at weaning. However, postnatal EO induced lower JAK2 and p-STAT3, and higher SOCS3 expression in adult animals, indicating central leptin resistance in adulthood. In conclusion, postnatal EO induces obesity, higher total and visceral fat mass, lower HDL-C and central leptin resistance in adult life. PMID- 20303732 TI - Modelling of slaughterhouse solid waste anaerobic digestion: determination of parameters and continuous reactor simulation. AB - A model based on the work of Angelidaki et al. (1993) was applied to simulate the anaerobic biodegradation of ruminal contents. In this study, two fractions of solids with different biodegradation rates were considered. A first-order kinetic was used for the easily biodegradable fraction and a kinetic expression that is function of the extracellular enzyme concentration was used for the slowly biodegradable fraction. Batch experiments were performed to obtain an accumulated methane curve that was then used to obtain the model parameters. For this determination, a methodology derived from the "multiple-shooting" method was successfully used. Monte Carlo simulations allowed a confidence range to be obtained for each parameter. Simulations of a continuous reactor were performed using the optimal set of model parameters. The final steady-states were determined as functions of the operational conditions (solids load and residence time). The simulations showed that methane flow peaked at a flow rate of 0.5-0.8 Nm(3)/d/m(reactor)(3) at a residence time of 10-20 days. Simulations allow the adequate selection of operating conditions of a continuous reactor. PMID- 20303733 TI - Fuzzy multicriteria disposal method and site selection for municipal solid waste. AB - The use of fuzzy multiple criteria analysis (MCA) in solid waste management has the advantage of rendering subjective and implicit decision making more objective and analytical, with its ability to accommodate both quantitative and qualitative data. In this paper a modified fuzzy TOPSIS methodology is proposed for the selection of appropriate disposal method and site for municipal solid waste (MSW). Our method is superior to existing methods since it has capability of representing vague qualitative data and presenting all possible results with different degrees of membership. In the first stage of the proposed methodology, a set of criteria of cost, reliability, feasibility, pollution and emission levels, waste and energy recovery is optimized to determine the best MSW disposal method. Landfilling, composting, conventional incineration, and refuse-derived fuel (RDF) combustion are the alternatives considered. The weights of the selection criteria are determined by fuzzy pairwise comparison matrices of Analytic Hierarchy Process (AHP). It is found that RDF combustion is the best disposal method alternative for Istanbul. In the second stage, the same methodology is used to determine the optimum RDF combustion plant location using adjacent land use, climate, road access and cost as the criteria. The results of this study illustrate the importance of the weights on the various factors in deciding the optimized location, with the best site located in Catalca. A sensitivity analysis is also conducted to monitor how sensitive our model is to changes in the various criteria weights. PMID- 20303735 TI - Detection of hybridization of single-strand DNA PCR products in temperature change process by a novel metal-clamping piezoelectric sensor. AB - Oligonucleotide probes on the sensor surface can be hybridized with single-strand DNA (ssDNA) that is formed from PCR products in ice bath after degeneration. Thus, detection of PCR products by piezoelectric sensors requires the participation of ssDNA PCR products in ice bath. When PCR products in ice bath are added into the buffer of the sensor well at room temperature, there will be a temperature change process during mixing. However, it still remains unclear whether the temperature change affects the frequency baseline stability of the sensor and the result judgment, which is the basic condition for detecting hybridization of nucleic acid. In this study, we detected the hybridization of HPV PCR products during temperature change process by a self-designed adjustable metal-clamping piezoelectric sensor. The study mainly involves sensor adjustment, probe immobilization and ice bath sample addition (at different concentrations and different volumes). The response curve of basic frequency in temperature change process showed three stages, i.e., increase, decrease to baseline, and continuous decrease to stability. The early increase of frequency and duration of the time can reach 55+/-7.4 Hz and 39 min when 40 microL sample (0-1 degrees C) was added into 110 microL buffer (25 degrees C). The frequency increase effect caused by temperature difference at early stage depends on the volume ratio of two liquids and on the temperature difference. The results indicate that we should pay more attention to possibly small volume of PCR products in ice bath and minor temperature difference of two liquids in operation. PMID- 20303736 TI - Ternary mixed monolayers for simultaneous DNA orientation control and surface passivation for label free DNA hybridization electrochemical sensing. AB - Target recognizing ternary mixed monolayer is constructed by simple sequential adsorption of thiol caped single stranded DNA (HS-ssDNA), 6-mercapto-1-hexanol (MCH) and 3-mercaptopropionic acid (MPA) diluents (abbreviated as HS ssDNA/MPA/MCH) and applied for detection of DNA hybridization sequence by electrochemical method. The method is more reliable and reproducible on both conventional wire electrode and 100 nm scale gold-coated silicon chips. Detection limit of 10 pM is observed constantly on all types of electrodes. This ternary layer approach provides 60-80% discrimination effect between the hybridized and un-hybridized surfaces compared to the binary mixed monolayers HS-ssDNA/MCH and HS-ssDNA/MPA that showed 20-30% only. Characterization by impedance spectroscopy, X-ray photoelectron spectroscopy and surface Fourier Transform Infrared (FT-IR) techniques reveals 'head-to-head' anisotropic hydrogen bonding between MPA and MCH diluents that controls the HS-ssDNA orientation and enhancing the electrostatic blockade for K3[Fe(CN)6]. This is the first report characterizing the ternary layer for DNA molecular affinity sensing. Results provided unprecedented insight onto the label free electrochemical sensing and understanding of the complex sensing mechanism to develop sensors that is more reliable. PMID- 20303737 TI - Photobiological production of hydrogen gas as a biofuel. AB - Solar energy can be converted into chemical energy in the form of hydrogen gas using oxygenic and anoxygenic photosynthetic microbes. Laboratory-scale measurements suggest that photobiological hydrogen production rates could yield more energy than current crop-based biofuel productivities. Major challenges, such as inhibitory amounts of oxygen produced during oxygenic photosynthesis and inhibition of H(2)-producing nitrogenase by ammonia, are being overcome through genetic engineering. Further advances are expected as the metabolic and regulatory aspects behind photobiological hydrogen production are revealed. Genetic engineering, coculturing, and bioreactor designs making use of immobilized cells have the potential to increase conversion efficiencies of light energy to H(2) and to decrease the land area needed for photobiological H(2) production. PMID- 20303738 TI - Predisposition alleles for Testicular Germ Cell Tumour. AB - For some time, it has been known that there is a substantial genetic component to testicular germ cell tumour susceptibility, supported by several pieces of evidence, including the significantly increased familial risk and differential risk among races. However, despite extensive linkage searches on available families, no high penetrance genes have been identified. Recently genome-wide association studies have revealed three candidate loci, which confer up to a four fold risk of developing TGCT. The genome-wide association studies for this cancer are noteworthy, because of the high effect sizes demonstrated at each loci and the biological plausibility of the genes at or near the associated SNPs, particularly KITLG. PMID- 20303740 TI - Designing ensembles in conformational and sequence space to characterize and engineer proteins. AB - Computational protein design - the search for amino acids that adopt defined structures and functions - has achieved significant successes in recent years. Design is often approached from the perspective of targeting the design objective one structure-sequence pair at a time. Here we summarize studies that take an alternate approach, considering design solutions from the perspective of conformational and sequence ensembles. We argue that this strategy both more closely mimics the properties of naturally occurring proteins and drives progress in engineering. We discuss benchmarks for evaluating design methods, highlight recent advances, and project how the evolving capabilities of gene sequencing, gene synthesis, and genome editing may change the design field. PMID- 20303739 TI - Heterogeneous reward signals in prefrontal cortex. AB - Neurons encode upcoming rewards throughout frontal cortex. Recent papers have helped to determine that these signals play different roles in different frontal regions. Neurons in orbitofrontal cortex (PFo) appear to be responsible for calculating the specific value of an expected reward, information that can help efficiently guide decision-making. Similar signals are also present in the cingulate sulcus (PFcs). By contrast, reward signals in lateral prefrontal cortex (PFl) are consistent with a role in using reward to guide other cognitive processes, such as the allocation of attentional resources and using value information to guide learning other relationships in the environment such as arbitrary stimulus-response mappings. A remaining issue for future work is to specify the precise roles of PFo and PFcs. These two areas show very different patterns of connectivity with other brain areas, and it is currently unclear how this effects their contribution to decision-making. PMID- 20303742 TI - CD44, a therapeutic target for metastasising tumours. AB - Members of the CD44 family of transmembrane glycoproteins, in particular CD44v6 isoforms, were shown to be metastatic determinants of rat pancreatic tumour cells back in the early 1990s. Furthermore, the expression of several CD44 proteins correlates with aggressive stages of various human cancers. Because of the frequent and homogeneous expression of CD44v6 isoforms in squamous cell carcinoma, antibodies recognising these proteins were used in clinical trials for patients suffering from head and neck squamous cell carcinoma (HNSCC). Although the phase I clinical trials looked promising, the studies were abruptly ended after the death of a patient. Despite the termination of the trials, CD44 certainly remains a valid target for anti-cancer therapy. In this review, alternative strategies targeting CD44 functions are presented. These functions include the binding to hyaluronan (HA), the collaboration with osteopontin and the contribution of CD44 isoforms to receptor tyrosine kinase (RTKs) activation. These new attempts led to the development of peptides that interfere for example with HA binding and that might be used to induce apoptosis in mammary carcinoma or to prevent homing of leukaemia stem cells. Other peptides block RTK activation and thereby inhibit tumour angiogenesis and metastatic spread. PMID- 20303741 TI - Targeting the HGF/Met signalling pathway in cancer. AB - Under normal conditions, hepatocyte growth factor (HGF)-induced Met tyrosine kinase (TK) activation is tightly regulated by paracrine ligand delivery, ligand activation at the target cell surface, and ligand activated receptor internalisation and degradation. Despite these controls, HGF/Met signalling contributes to oncogenesis and tumour progression in several cancers and promotes aggressive cellular invasiveness that is strongly linked to tumour metastasis. The prevalence of HGF/Met pathway activation in human malignancies has driven rapid growth in cancer drug development programmes. Pathway inhibitors can be divided broadly into biologicals and low molecular weight synthetic TK inhibitors; of these, the latter now outnumber all other inhibitor types. We review here the basic properties of HGF/Met pathway antagonists now in preclinical and clinical development as well as the latest clinical trial results. The main challenges facing the effective use of HGF/Met-targeted antagonists for cancer treatment include optimal patient selection, diagnostic and pharmacodynamic biomarker development, and the identification and testing of optimal therapy combinations. The wealth of basic information, analytical reagents and model systems available concerning HGF/Met oncogenic signalling will continue to be invaluable in meeting these challenges and moving expeditiously toward more effective disease control. PMID- 20303743 TI - Doubling time of serum CA125 is an independent prognostic factor for survival in patients with ovarian cancer relapsing after first-line chemotherapy. AB - INTRODUCTION: Confirmed doubling of CA125 value is one definition of progression in ovarian cancer patients. If asymptomatic, the management of these patients is unclear. To provide information which may assist in therapeutic decision making, we set out to determine the independent prognostic significance for the rate of rise in CA125 during surveillance in ovarian cancer patients as measured by CA125 doubling time. PATIENT AND METHODS: Clinical information was obtained through a 2 staged chart review of ovarian cancer patients treated in our department from 1994 to 2003. We searched for patients who met criteria for CA125 progression and doubling during surveillance following first-line therapy. RESULTS: A total of 296 patients were initially identified. During surveillance, the median doubling time of CA125 was 40 d and the median survival for patients with a CA125 doubling time of 40 d was 10.6 months compared to 22.1 months for those with doubling time>40 d. In a univariate analysis, age, high-grade, suboptimal cytoreduction, short CA125 doubling time, short time to progression and high CA125 at progression were significantly associated with poor survival, but in a multivariate analysis, a short CA125 doubling time of 2M NaCl, grew also in media with salinities ranging between 1 and 4M NaCl, with optimum growth between 1 and 2M NaCl. With the exception of the two archaeal genera, all isolates could grow in a nitrogen-free medium. The total rhizospheric and phyllospheric microbial consortia could attenuate crude oil in complete (nitrogen-containing) medium, but also equally well in a nitrogen-free medium. It was concluded that H. strobilaceum could be a valuable halophyte for phytoremediation of oil-polluted hypersaline environments via rhizosphere technology. PMID- 20303748 TI - Field scale molecular analysis for the monitoring of bacterial community structures during on-site diesel bioremediation. AB - A diesel contaminated groundwater site was surveyed using 16S rRNA gene based analyses to investigate the effect of bioaugmentation on the bacterial communities present. The analyses included the use of denaturing gradient gel electrophoresis (DGGE) to profile microbial community structure and the construction and sequencing of clone libraries in order to identify the organisms present. Community analyses revealed a high degree of similarity in the inoculated compartments during bioaugmentation, not observed once inoculation had ceased. However, it was also shown that there was very little community similarity between the inoculum and the inoculated samples. Instead, the similarity seen during the application of the bioaugmentation treatment was thought to be due to nutrient addition applied along with the inoculum. Furthermore, once the bioaugmentation treatment had ceased the communities around the site became more diverse, suggesting that the hierarchical structure seen during treatment was due to the stimulation of a group of opportunistic indigenous organisms by the nutrients added. The findings not only highlight the importance of monitoring the fate of inocula used in bioaugmentation but also how crucial the process of the selection of species and the culture conditions used in the construction of these consortia. PMID- 20303747 TI - Competitive biosorption of Yellow 2G and Reactive Brilliant Red K-2G onto inactive aerobic granules: simultaneous determination of two dyes by first-order derivative spectrophotometry and isotherm studies. AB - This study focused on the competitive biosorption of Yellow 2G (Y2G) and Reactive Brilliant Red K-2G (RBR) by inactive aerobic granules in binary solutions. A first-order derivative spectrophotometric method for the simultaneous determination of Y2G and RBR in binary solutions was developed. Dubinin Raduskevich (D-R) isotherm successfully predicted the biosorption of Y2G and RBR in both single and binary solutions. However, none of the tested binary adsorption isotherms could realistically represent the biosorption equilibrium data. Maximum biosorption capacity calculated from D-R isotherm for Y2G and RBR in single solution was 58.50 and 66.18 mg g(-1), respectively; in binary solutions, for Y2G it decreased to 40.38 mg g(-1), but for RBR it increased to 171.21 mg g(-1), showing their synergism and antagonistic interactions. The FTIR results indicated the main functional groups on aerobic granules for biosorption of Y2G and RBR would be amine, hydroxyl, carboxyl and either. PMID- 20303749 TI - Lignocellulosic bioethanol: current status and perspectives. PMID- 20303750 TI - Agro-industrial residues as low-price feedstock for diesel-like fuel production by thermal cracking. AB - Pyrolysis of industrial fatty wastes (soybean soapstock, beef tallow, and poultry industry waste) was carried out in the absence of catalysts. In all cases, organic mixtures of hydrocarbons and oxygenated compounds were obtained. These mixtures were distilled and diesel-like fractions were isolated and characterized by GC-FID, GC-MS and FT-IR, showing the formation of olefins, paraffins, and some oxygenated compounds such as carboxylic acids and esters. The main physical chemical properties of those isolated diesel-like fuels (density, viscosity, distillation curve, carbon residue, copper corrosion test, cetane index, cold finger plugging point, acid index and heating value) were determined using ASTM standard methods and matched the Brazilian specification for diesel fuel. PMID- 20303751 TI - Conformationally-restricted amino acid analogues bearing a distal sulfonic acid show selective inhibition of system x(c)(-) over the vesicular glutamate transporter. AB - A panel of amino acid analogs and conformationally-restricted amino acids bearing a sulfonic acid were synthesized and tested for their ability to preferentially inhibit the obligate cysteine-glutamate transporter system x(c)(-) versus the vesicular glutamate transporter (VGLUT). Several promising candidate molecules were identified: R/S-4-[4'-carboxyphenyl]-phenylglycine, a biphenyl substituted analog of 4-carboxyphenylglycine and 2-thiopheneglycine-5-sulfonic acid both of which reduced glutamate uptake at system x(c)(-) by 70-75% while having modest to no effect on glutamate uptake at VGLUT. PMID- 20303752 TI - 1,7-Disubstituted oxyindoles are potent and selective EP(3) receptor antagonists. AB - A series of novel 1,7-disubstituted oxyindoles were shown to be potent and selective EP(3) receptor antagonists. Variation of substitution pattern at the C 3 position of indole enhanced in vitro metabolic stability of the resulting derivatives. Series 27a-c showed >1000-fold selectivity over a panel of prostanoid receptors including IP, FP, EP(1), EP(2) and EP(4). These agents also featured low CYP inhibition and good activity in the functional rat platelet aggregation assay. PMID- 20303753 TI - A novel D-glucose derivative radiolabeled with technetium-99m: synthesis, biodistribution studies and scintigraphic images in an experimental model of Ehrlich tumor. AB - A d-glucose-MAG(3) derivative was successfully synthesized and radiolabeled in high labeling yield. Biodistribution studies and scintigraphic images in Ehrlich tumor-bearing mice were performed. This compound showed high accumulation in tumor tissue with high tumor-to-muscle ratio. Thus, d-glucose-MAG(3) could be considered as agent for tumor diagnosis. PMID- 20303754 TI - Praziquantel analogs with activity against juvenile Schistosoma mansoni. AB - Six amide and four urea derivatives of praziquantel were synthesized and tested for antischistosomal activity against juvenile and adults stages of Schistosoma mansoni in infected mice. Only one of these had significant activity against adult worms, but, unlike praziquantel, six of these had low to modest activity against juvenile worms. A praziquantel ketone derivative had the best combination of activity against juveniles and adults, but it had no effect on the motility of adult S. mansoni in ex vivo culture. Cytochrome P450 metabolic stability data support the hypothesis that the major trans-cyclohexanol metabolite of praziquantel plays an important role in the antischistosomal activity of this drug. PMID- 20303755 TI - Synthesis, cytotoxic activity and structure-activity relationships of hedychenone analogues. AB - Hedychenone, a plant-derived labdane diterpenoid, showed potent in vitro cytotoxic activity against cancerous cells. In the present study, a series of analogues have been synthesized by modification of the furanoid ring, double bond and the vinylic methyl functionality of this natural product lead and evaluated for their cytotoxic activities against human cancer cell lines. The structures of the target compounds were established by IR, (1)H NMR and mass spectral analysis. Majority of the analogues displayed potent activity than the parent compound, hedychenone. Preliminary structure-activity relationship studies indicated that furanoid ring has a greater impact on cytotoxicity than that of the decalone nucleus. However, dimerization through C-8 significantly enhanced the cytotoxic activity of the hedychenone. PMID- 20303756 TI - The introduction of P4 substituted 1-methylcyclohexyl groups into Boceprevir: a change in direction in the search for a second generation HCV NS3 protease inhibitor. AB - In the search for a second generation HCV protease inhibitor, molecular modeling studies of the X-ray crystal structure of Boceprevir1 bound to the NS3 protein suggest that expansion into the S4 pocket could provide additional hydrophobic Van der Waals interactions. Effective replacement of the P4 tert-butyl with a cyclohexylmethyl ligand led to inhibitor 2 with improved enzyme and replicon activities. Subsequent modeling and SAR studies led to the pyridine 38 and sulfone analogues 52 and 53 with vastly improved PK parameters in monkeys, forming a new foundation for further exploration. PMID- 20303757 TI - Cap myopathy caused by a mutation of the skeletal alpha-actin gene ACTA1. AB - Cap myopathy is a congenital myopathy with cap-like structures under the sarcolemma. Mutations in TPM2 and TPM3 genes have been reported in cap myopathy so far. We report a newborn boy with persistent profound weakness who required gastro-jejunal tube feeding, tracheostomy and life-long ventilation until he died at 5 years of age. Muscle biopsy at 5 weeks of age was uninformative. Repeat biopsy at 4.5 years revealed subsarcolemmally located caps that were immunopositive for alpha-actinin, actin and to some extent, desmin. EM confirmed loosely arranged thin filaments and paucity of thick filaments. Molecular analysis of ACTA1 gene identified a novel de novo Met49Val [corrected] mutation. In addition to a new ACTA1 gene mutation, our case emphasizes the genetic heterogeneity of cap myopathy and its association with ACTA1 gene as well as the importance of repeat muscle biopsy in patients with undiagnosed muscle weakness. PMID- 20303759 TI - Bilateral balance impairments after lateral ankle trauma: a systematic review and meta-analysis. AB - Research indicates that balance is impaired in the involved limb following an ankle injury. However, bilateral balance impairments are a viable reason for previous non-significant findings between involved and uninvolved limbs. The purpose of this investigation was to conduct a meta-analysis on studies reporting the effects of lateral ankle trauma on balance of the involved and uninvolved limb after acute ankle injury and chronic ankle instability. Twelve studies qualified for inclusion and assessed static balance for both the involved and uninvolved limbs post-injury and a control group. Meta-analyses calculated standardized mean difference effects and explored moderating variables for the involved and uninvolved limbs relative to controls. A significant cumulative effect size (ES=0.448, p<0.00001) indicated that balance of the involved limb is impaired after a history of ankle injury. Moderator variable analysis revealed that both acute (ES=0.529, p<0.0002) and chronic (ES=0.338, p<0.001) lateral ankle trauma negatively affected balance. Analysis of the uninvolved limb also revealed postural stability impairments (ES=0.275, p<0.003). Additional, moderator analysis showed a significant acute effect (ES=0.564, p<0.0001), but failed to find significance for individuals with chronic ankle instability (ES=0.070, p=0.552). These findings provide strong evidence that balance is bilaterally impaired after an acute lateral ankle sprain. However, these findings suggest that bilateral balance deficits are not present in patients with chronic ankle instability. Based on these findings, the uninvolved limb should not be used as a reference for "normal balance" following an acute lateral ankle sprain. Further, patients with acute lateral ankle sprains should undergo balance training on both limbs. PMID- 20303760 TI - Treatment of symptomatic interhemispheric arachnoid cysts by cystoperitoneal shunting. AB - Arachnoid cysts (AC) located within the interhemispheric fissure are rare, frequently associated with agenesis or hypogenesis of the corpus callosum. The optimal method for surgical treatment is under debate. In this study, we retrospectively reviewed the clinical results of seven infants (five males, two females; mean age, 5.1 months) with large interhemispheric AC who underwent cystoperitoneal shunting (CP) and evaluated the long-term efficacy in terms of clinical data, psychomotor development and neuroimaging. All patients were symptomatic and operated on before they reached 1 year of age. In three patients, additional ventricular catheters were inserted due to concomitant hydrocephalus. The additional catheters were joined with the cyst catheters and the peritoneal catheters with Y-shaped connectors in the same session. The patients were followed up for an average of 57 months (range 24-120 months). The clinical and developmental outcome was good in most patients with complete resolution of symptoms and signs. The developmental outcome scale, which included cognitive and psychomotor development, was "good" (normal) or "fair" (near normal) for six of seven patients. Radiologically, the cyst was completely or nearly totally resolved in five patients, and partially resolved in two. In these symptomatic patients with interhemispheric AC, CP shunting provided favorable treatment outcomes with complete or near-total resolution of symptoms and reduction in cyst size or disappearance of the cyst. PMID- 20303758 TI - p53 and ARF: unexpected players in autophagy. AB - p53 and ARF are well-established tumor-suppressor proteins that function together in the negative regulation of cancer. Recently, both proteins were found to play surprising roles in autophagy. Autophagy ('self-eating') is a crucial response of eukaryotic cells to metabolic and other stress. During this process, portions of the cytosol are sequestered into characteristic double-membrane vesicles that are delivered to the lysosome for degradation, leading to the release of free amino acids and promoting cell survival. The mechanisms whereby p53 and ARF control autophagy are only now becoming elucidated. An emerging question is whether we can develop metabolic poisons that preferentially destroy tumor cells depending on their reliance on autophagy for survival, and on their p53 and ARF status. PMID- 20303761 TI - Primary angiitis of the central nervous system with diffuse cerebral mass effect and giant cells. AB - Primary angiitis of the central nervous system (PACNS), also called primary CNS vasculitis, is an idiopathic inflammatory condition affecting only intracranial and spinal cord vessels, particularly medium-sized and smaller arteries and arterioles. Angiography and histopathology typically do not reveal evidence of systemic vasculitis.(1,2) Histopathology usually reveals granulomatous inflammation affecting arterioles and small arteries of the parenchyma and/or leptomeninges, similar to that seen in Takayasu's or giant cell arteritis.(1-3) We report a patient with biopsy-proven PACNS with giant cells and cerebral mass effect on MRI. Magnetic resonance angiography and cerebral angiography appeared normal and there was no evidence of extracranial vasculitis. PMID- 20303762 TI - Treatment of delayed-onset post-stroke monochorea with stereotactic pallidotomy. AB - Chorea that occurs as a result of a stroke is rare. We report a patient who developed hemiplegia following an acute hemorrhagic stroke in the left cerebral peduncle and subthalamus; although he had recovered gradually from the severe limb weakness, monochorea occurred 6 months later. Pallidotomy eliminated this symptom and we found it is a safe treatment for medically intractable post-stroke chorea after hemiplegia has resolved. PMID- 20303763 TI - Cardiovascular autonomic function tests to provide normative data from a healthy older population. AB - We aimed to derive normative data for cardiovascular autonomic function tests (AFT) in an older population using new measures. The AFT were performed in 48 healthy control subjects. The average heart rate (HR) response to deep breathing (DB) (HR(DB)), Valsalva ratio (VR), magnitude of the HR and blood pressure (BP) response of different phases of the Valsalva maneuver, BP recovery times (PRT 100 and PRT 50) and HR and BP changes on head-up tilting were calculated. The mean age (+/-standard deviation) of study participants was 58+/-14.5 years (range 20 82 years), of whom 29 (60%) were men. The systolic blood pressure (SBP) early phase 2 amplitude showed an inverse relationship with age (p=0.03). There was a trend for progressive attenuation of SBP late phase 2 amplitude with age (p=0.09). The systolic BP recovery time was not affected by age, gender or body mass index. We concluded that age has a significant effect on most AFT variables. Age and gender did not influence the systolic BP recovery time; hence, systolic BP recovery time could be useful in the evaluation of adrenergic failure. PMID- 20303764 TI - Longstanding knee joint preserved functional outcome following medial femoral condyle resection. A case report. AB - Giant cell tumor of the bone (GCT) is a relatively uncommon benign aggressive tumor that occurs near the articular surface of major joints. Standard treatment of GCT is comprised of local resection followed by local adjuvant therapy. Unicondylar osteoarticular resection is usually followed by a reconstructive procedure to restore the biomechanical demands of the joint. The present report describes a patient with satisfactory knee stability and functional outcome 32 years following medial femoral condyle resection with no reconstructive arthroplasty. PMID- 20303765 TI - The Bi-Surface total knee arthroplasty: minimum 10-year follow-up study. AB - The Bi-Surface Knee System (Japan Medical Material, Kyoto, Japan), which has a unique ball-and-socket joint and whose femoral component is made from alumina ceramic, was designed to improve deep knee flexion and long-term durability after total knee arthroplasty. The purpose of this study was to review the clinical results of a minimum 10-year follow-up. Between 1989 and 1997, 507 total knee arthroplasties were carried out in 371 patients. Forty three patients (56 knees) were lost to follow-up. The mean age of the patients at operation was 68.5 years, and the patients were followed up for a mean of 11.7 years. The knees were evaluated on the basis of Knee Society knee score and functional score, radiographs, and Kaplan-Meier survivorship analysis. The knee score was improved from 38.9+/-17.4 points preoperatively to 93.3+/-7.8 points at the latest follow up (p<0.001). The functional score was improved from 34.9+/-19.3 points to 52.7+/ 24.1 points (p<0.001). The mean range of flexion was improved from 118.7+/-21.7 degrees to 124.2+/-20.8 degrees (p<0.001). The critical angle, which means the border to gain more range of flexion postoperatively, was 130.1 degrees. Kaplan Meier survivorship at 10-year was 95.9% with any operation or radiographic failure as the end point. The corresponding rate was 97.4% with revision of any component as the end point. No ceramic component fracture occurred. The present study demonstrates that good range of flexion was maintained for a long time after total knee arthroplasty with excellent durability. The Bi-Surface Knee System appears to have achieved its design objectives. PMID- 20303766 TI - Post-traumatic chylous knee effusion. AB - Chylous joint effusion is a rare condition in which synovial fluids containing large amounts of lipids take on a milky appearance as a result. We report on a 19 year-old male patient with posttraumatic chylous knee effusion. Several days after striking his knee against the ground because of a traffic accident, his left knee showed obvious swelling. Aspiration of his knee was performed, yielding 70ml of purulent-appearing fluid. To distinguish this condition from purulent or tuberculosis arthritis, arthroscopic biopsy and debridement were performed. Arthroscopic examination visualized distinctive yellow-white soft lesions covering much of the joint capsule, resembling a cobweb. Tissue cultures for bacteria were negative. Pathologically, we identified clusters of xanthoma cells with fibrin exudation due to disruption of the synovium and intra-articular fat pad necrosis. Centrifuging the aspiration fluid yielded a thick creamy lipid layer as the supernatant. A fresh drop preparation showed that the specimen contained innumerable fat globules, which stained red with oil red O stain. The patient was able to walk without difficulty or further swelling of his knee at the end of the second postoperative week. Posttraumatic chylous effusion is self limited. Purulent arthritis or tuberculosis arthritis, however, should still be the presumptive diagnosis in such cases. Arthroscopic irrigation and debridement should be considered for these traumatic cases to confirm diagnosis and to speed up recovery. PMID- 20303767 TI - Assessing the trypanocidal potential of natural and semi-synthetic diketopiperazines from two deep water marine-derived fungi. AB - Human African trypanosomiasis (HAT, commonly known as African sleeping sickness) is categorized as a neglected disease, as it afflicts >50,000 people annually in sub-saharan Africa, and there are few formal programs in the world focused on drug discovery approaches for this disease. In this study, we examined the crude extracts of two fungal strains (Aspergillus fumigatus and Nectria inventa) isolated from deep water sediment which provided >99% growth inhibition at 1microg/mL of Trypanosoma brucei, the causative parasite of HAT. A collection of fifteen natural products was supplemented with six semi-synthetic derivatives and one commercially available compound. Twelve of the compounds, each containing a diketopiperazine core, showed excellent activity against T. brucei (IC(50)=0.002 40microM), with selectivity over mammalian cells as great as 20-fold. The trypanocidal diketopiperazines were also tested against two cysteine protease targets Rhodesain and TbCatB, where five compounds showed inhibition activity at concentrations less than 20microM. A preliminary activity pattern is described and analyzed. PMID- 20303768 TI - Investigating the anti-proliferative activity of styrylazanaphthalenes and azanaphthalenediones. AB - A group of styrylazanaphthalenes and azanaphthalenediones were synthesized and tested for their anti-proliferative activity. Most of the compounds were obtained with the use of microwave-assisted synthesis. The lipophilicity of the compounds was measured by RP-HPLC and their anti-proliferative activity was assayed against the human SK-N-MC neuroepithelioma and HCT116 human colon carcinoma cell lines. Active compounds were also tested in clonogenity and comet assays. Several quinazolinone and styrylquinazoline analogues were found to have markedly greater anti-proliferative activity than desferoxamine and cis-platin. PMID- 20303769 TI - (18)F Labeled benzimidazole derivatives as potential radiotracer for positron emission tomography (PET) tumor imaging. AB - This article reported the synthesis and bioevaluation of two [(18)F] labeled benzimidazole derivatives, 4-(5-(2-[(18)F] fluoro-4-nitrobenzamido)-1-methyl-1H benzimidazol-2-yl) butanoic acid ([(18)F] FNBMBBA, [(18)F]a1) and 3-(2 fluoroethyl)-7-methyl-2-propyl-3H-benzimidazole-5-carboxylic acid ([(18)F] FEMPBBA, [(18)F]b1) for PET tumor imaging. The preparation [(18)F] FEMPBBA was completed in 1h with overall radiochemical yield of 50-60% (without decay corrected). Biodistribution assay in S180 tumor bearing mice of both compounds were carried out, and the results are both meaningful. [(18)F] FEMPBBA which can be taken as a revision of [(18)F] FNBMBBA got an excellent result, and has significant advantages in some aspects compared with L-[(18)F] FET and [(18)F] FDG in the same animal model, especially in tumor/brain uptake ratio. The tumor/brain uptake ratio of [(18)F] FEMPBBA gets to 4.81, 7.15, and 9.8 at 30min, 60min and 120min, and is much higher than that of L-[(18)F] FET (2.54, 2.92 and 2.95) and [(18)F]-FDG (0.61, 1.02, 1.33) at the same time point. The tumor/muscle and tumor/blood uptake ratio of [(18)F] FEMPBBA is also higher than that of L [(18)F] FET at 30min and 60min. This result indicates compound [(18)F] FEMPBBA is a promising radiotracer for PET tumor imaging. PMID- 20303770 TI - Synthesis of 26-hydroxy-22-oxocholestanic frameworks from diosgenin and hecogenin and their in vitro antiproliferative and apoptotic activity on human cervical cancer CaSki cells. AB - Certain steroidal compounds have demonstrated an antiproliferative effect against several tumor cell lines; however, their complete role on cancer cells is not currently established. Herein, we report the synthesis and evaluation of two new 26-hydroxy-22-oxocholestanic steroids on cervical cancer CaSki cells. The title compounds were prepared from diosgenin and hecogenin in excellent yields. We determined their effect on cell proliferation, cell cycle, and cell death. The cytotoxic effect of the title compounds on CaSki and human lymphocytes was also evaluated, indicating that the main cell death process is not necrosis; the null effect on lymphocytes implies that they are not cytotoxic. The observation of apoptotic bodies as well as the increase in the expression of active caspase-3 along with the fragmentation of DNA confirmed that such new cholestanic frameworks induced apoptosis in tumor cells. Significantly, their antiproliferative activity on tumor cells did not affect the proliferative potential of normal fibroblasts from cervix and peripheral blood lymphocytes. The title compounds show selective antitumor activity and therefore serve as promising lead candidates for further optimization. PMID- 20303771 TI - Novel 8-(furan-2-yl)-3-substituted thiazolo [5,4-e][1,2,4] triazolo[1,5-c] pyrimidine-2(3H)-thione derivatives as potential adenosine A(2A) receptor antagonists. AB - Novel thiazolotriazolopyrimidine derivatives (23-33) designed as potential adenosine A(2A) receptor (A(2A)R) antagonists were synthesized. Molecular docking studies revealed that all compounds (23-33) exhibited strong interaction with A(2A)R. The strong interaction of the compounds (23-33) with A(2A)R in silico was confirmed by their high binding affinity with human A(2A)R stably expressed in HEK293 cells using radioligand-binding assay. The compounds 24-26 demonstrated substantial binding affinity and selectivity for A(2A)R as compared to SCH58261, a standard A(2A)R antagonist. Decrease in A(2A)R-coupled release of endogenous cAMP in treated HEK293 cells demonstrated in vitro A(2A)R antagonist potential of the compounds 24-26. Attenuation in haloperidol-induced motor impairments (catalepsy and akinesia) in Swiss albino male mice pre-treated with compounds 24 26 further supports their role in the alleviation of PD symptoms. PMID- 20303772 TI - Structural development studies of anti-hepatitis C virus agents with a phenanthridinone skeleton. AB - A phenanthridinone skeleton was derived from our previous researches on thalidomide and retinoids as a multi-template for generation of anti-viral lead compounds. Structural development studies focusing on anti-hepatitis C virus activity afforded 5-butyl-2-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2 yl)phenanthridin-6(5H)-one (10) and 5-butylbenzo[b]phenanthridin-6(5H)-one (39), which showed EC(50) values of approximately 3.7 and 3.2microM, respectively. PMID- 20303773 TI - Intrinsic error of the point-source and the LS-curve approximations in treatment of true coincidence summing. AB - Apart from an experimental determination of the relevant correction factors or a full Monte Carlo simulation, the most popular computational approach to the problem of true coincidence summing effects is the point-source approximation. An improvement of this method is based on the so-called linear-to-square or "Third curve" of gamma-ray spectrometry. Both of these computational methods carry with them an intrinsic error, the magnitude of which we investigate for the case of environmental measurements with p-type HPGe detectors. PMID- 20303774 TI - Nitrate uptake and utilization is modulated by exogenous gamma-aminobutyric acid in Arabidopsis thaliana seedlings. AB - Exogenously applied GABA modulates root growth by inhibition of root elongation when seedlings were grown in vitro on full-strength Murashige and Skoog (MS) salts, but root elongation was stimulated when seedlings were grown on 1/8 strength MS salts. When the concentration of single ions in MS salts was individually varied, the control of growth between inhibition and stimulation was found to be related to the level of nitrate (NO(3)(-)) in the growth medium. At NO(3)(-) concentrations below 40 mM (full-strength MS salts level), root growth was stimulated by the addition of GABA to the growth medium; whereas at concentrations above 40 mM NO(3)(-), the addition of GABA to the growth medium inhibited root elongation. GABA promoted NO(3)(-) uptake at low NO(3)(-), while GABA inhibited NO(3)(-) uptake at high NO(3)(-). Activities of several enzymes involved in nitrogen and carbon metabolism including nitrate reductase (NR), glutamine synthetase (GS), glutamate synthase (NADH-GOGAT), NADP-dependent isocitrate dehydrogenase (NADP-ICDH), and phosphoenol pyruvate carboxylase (PEPCase) were regulated by GABA in the growth medium. Supplementing 1/8 strength MS medium with 50 mM GABA enhanced the activities of all of the above enzymes except ICDH activities in root tissues. However, at full-strength MS, GABA showed no inhibitory effect on the activities of these enzymes, except on GS in both root and shoot tissues, and PEPCase activity in shoot tissues. Exogenous GABA increased the amount of NR protein rather than its activation status in the tissues. This study shows that GABA affects the growth of Arabidopsis, possibly by acting as a signaling molecule, modulating the activity of enzymes involved in primary nitrogen metabolism and nitrate uptake. PMID- 20303775 TI - Oxidative metabolism, ROS and NO under oxygen deprivation. AB - Oxygen deprivation, in line with other stress conditions, is accompanied by reactive oxygen (ROS) and nitrogen species (RNS) formation and is characterised by a set of metabolic changes collectively named as the 'oxidative stress response'. The controversial induction of oxidative metabolism under the lack of oxygen is necessitated by ROS and RNS signaling in the induction of adaptive responses, and inevitably results in oxidative damage. To prevent detrimental effects of oxidative stress, the levels of ROS and NO are tightly controlled on transcriptional, translational and metabolic levels. Hypoxia triggers the induction of genes responsible for ROS and NO handling and utilization (respiratory burst oxidase, non-symbiotic hemoglobins, several cytochromes P450, mitochondrial dehydrogenases, and antioxidant-related transcripts). The level of oxygen in the tissue is also under metabolic control via multiple mechanisms: Regulation of glycolytic and fermentation pathways to manage pyruvate availability for respiration, and adjustment of mitochondrial electron flow through NO and ROS balance. Both adaptive strategies are controlled by energy status and aim to decrease the respiratory capacity and to postpone complete anoxia. Besides local oxygen concentration, ROS and RNS formation is controlled by an array of antioxidants. Hypoxic treatment leads to the upregulation of multiple transcripts associated with ascorbate, glutathione and thioredoxin metabolism. The production of ROS and NO is an integral part of the response to oxygen deprivation which encompasses several levels of metabolic regulation to sustain redox signaling and to prevent oxidative damage. PMID- 20303776 TI - Tissue engineering and biotechnology in general thoracic surgery. AB - Public interest in the recent progress of tissue engineering, a special line of biotechnology, makes the current review on thoracic surgery highly relevant. In this article, techniques, materials and cellular processes are discussed alongside their potential applications in tissue repair. Different applications of tissue engineering in tracheo-bronchial replacement, lung tissue cultures and chest-wall reconstruction are also summarised in the article. Potential tissue engineering-based solutions for destructive, chronic lung-injury-related conditions and replacement of tubular structures in the central airways are also examined. PMID- 20303777 TI - Long-term results of the frozen elephant trunk technique for extended aortic arch disease. AB - OBJECTIVES: This study describes the long-term safety and effectiveness of extended aortic arch replacement with the frozen elephant trunk technique from our 12 years of experience. METHODS: Between September 1997 and September 2008, 156 patients (mean age 67.9 years) with different pathologies from the aortic arch to the extended descending aorta in 100 dissections (acute A/acute B/chronic B=66/26/8) and 56 thoracic arteriosclerotic aneurysms (TAAs) had the frozen elephant technique performed upon them. During moderate hypothermic circulation with selective cerebral perfusion, the stent graft was inserted through the transected proximal aortic arch with trans-oesophageal echo guidance. RESULTS: Six patients (3.2%) (acute A/acute B/chronic B/TAA=3/2/0/1) died in hospital. Postoperative morbidity induced four (2.6%) strokes (acute A/acute B/chronic B/TAA=2/0/0/2) and three (2.0%) spinal injuries (paraplegia in two and transient paraparesis in one) (acute A/acute B/chronic B/TAA=0/0/1/2). In the long-term follow-up (mean 63.3 + or - 39.2 months, maximum 144 months) 16 patients died. The survival rate was 99.3%, 86.5% and 74.9% at 1, 5 and 10 years, respectively. An additional operation was performed in 15 (9.4%) (ascending aorta/aortic root/descending aorta/abdominal aorta=1/2/5/7) including three stent-graft related events (2.1%), and the additional repair proved successful. A follow-up computed tomography (CT) image was available for 96.0% (143/149) of patients who survived longer than 12 months. The size of false lumen or aneurysm increased in four patients, was unchanged in 20 patients (14.0%), shrank in 66 (46.2%) and was completely obliterated in 55 (37.1%). CONCLUSIONS: The frozen elephant technique could be an attractive treatment for extended aortic arch disease to the extended descending aorta for acute aortic dissection as well as arteriosclerotic aneurysm. PMID- 20303778 TI - Diffuse large B-cell lymphoma in the older. AB - The incidence of diffuse large B-cell lymphoma (DLCL) in the older is growing to the point of becoming a health priority in the next decades. Prognostic factors and the biology of the tumor are not very different between younger and older populations. Furthermore, it seems that the response rate is basically similar in both populations, provided an appropriate dose of chemotherapy is administered. However, there seem to be differences with regard to a lower tolerance to treatment and a higher relapse rate in responsive older patients. To analyze these problems we review the most important differences between young and older DLCL patients in terms of immunologic status, treatment toxicity and the presence of other concomitant diseases or organ dysfunctions. We also consider the most relevant clinical studies that may allow us to make the appropriate decisions regarding DLCL therapy in this older population. PMID- 20303779 TI - The hypothalamic clock and its control of glucose homeostasis. AB - The everyday life of mammals, including humans, exhibits many behavioral, physiological and endocrine oscillations. The major timekeeping mechanism for these rhythms is contained in the central nervous system (CNS). The output of the CNS clock not only controls daily rhythms in sleep/wake (or feeding/fasting) behavior but also exerts a direct control over glucose metabolism. Here, we show how the biological clock plays an important role in determining early morning (fasting) plasma glucose concentrations by affecting hepatic glucose production and glucose uptake, as well as glucose tolerance, by determining feeding-induced insulin responses. Recently, large-scale genetic studies in humans provided the first evidence for the involvement of disrupted (clock gene) rhythms in the pathogenesis of type 2 diabetes. PMID- 20303780 TI - Interferon-alpha and interleukin-6 in SLE serum induce the differentiation and maturation of dendritic cells derived from CD34+ hematopoietic precursor cells. AB - The objective of this study was to investigate the effects of the cytokines IFN alpha, IL-6 and IL-10 present in the serum of systemic lupus erythematosus (SLE) patients on the differentiation and maturation of DCs derived from CD34(+) hematopoietic precursor cells (HPCs). CD34(+) HPCs cultured in SLE serum containing elevated levels of IFN-alpha or IL-6 differentiated into DCs showing an increased expression of HLA-DR, CD80 and CD86, decreased IL-12 secretion along with increased IL-10 production, and an increased ability to stimulate allogenic T-cell proliferation, compared with DCs cultured in normal serum. DCs cultured with high levels of IFN-alpha increased the proportion of both CD3(+)CD8(-)IFN gamma(+) and CD3(+)CD8(+)IFN-gamma(+) T-cell subsets, and increased the production of IFN-gamma in the allogenic MLR. DCs cultured with high levels of IL 6 decreased the proportion of both IFN-gamma(+) T-cell subsets, and decreased the secretion of IFN-gamma, but increased the production of IL-10. The IL-10 present in SLE serum did not significantly alter the phenotype or function of the DCs. IFN-alpha and IL-6 present in SLE serum induce CD34(+) HPCs to differentiate into DCs with different regulatory effects on T-cell differentiation, which might be involved in the initiation and maintenance of SLE. PMID- 20303781 TI - TNFSF9 expression in primary biliary cirrhosis and its clinical significance. AB - Primary biliary cirrhosis (PBC) is a TH1/Th17 biased autoimmune disease of the medium and small bile ducts. The role of the costimulatory TNFSF9 (4-1BBL) in PBC progress was investigated by comparing its cell surface expression in peripheral blood mononuclear cells (PBMC) by flow cytometry, its mRNA expression in PBMCs by QRT-PCR and its serum concentrations in PBC patients vs. healthy controls. The TNFSF9 expression levels were compared with Mayo risk scores, PBC stages, IL-18 serum levels, total bilirubin (TBIL), and gamma glutamyltransferase (gamma-GT). The PBC patients expressed significantly greater levels of membrane bound TNFSF9, mRNA on peripheral blood mononuclear cells (PBMC), and soluble TNFSF9 (P<0.05) than healthy controls. Stage III and IV PBC subjects showed significantly reduced TNFSF9 mRNA than stage I and II. The TBIL, gamma-GT, and IL-18 were greatly increased in PBC patients compared with healthy controls. Stage II, III, and IV patients exhibited significantly higher IL-18 levels than stage I subjects. TNFSF9 mRNA significantly correlated with serum TBIL, gamma-GT, and IL-18 (P<0.05, P<0.01, P<0.01). Thus, TNFSF9 mRNA levels in PBMC may be associated with PBC progression, provide new clues for monitoring its condition and pathogenesis. PMID- 20303782 TI - Interleukin-6 produced in subcutaneous adipose tissue is linked to blood pressure control in septic patients. AB - Cytokines are inflammatory mediators of major relevance during sepsis. Recent evidence shows that adipose tissue can produce many distinct cytokines under physiological and pathological conditions, but the role of cytokines produced in adipose tissue was not addressed in sepsis. In the present study the open-flow microperfusion (OFM) technique was used to investigate whether the cytokines produced in subcutaneous adipose tissue (SAT) of patients with severe sepsis correlate with clinical variables. Interstitial fluid effluent samples were collected using an OFM catheter inserted in the abdominal SAT of nine patients with severe sepsis. Blood samples were withdrawn concomitantly and interleukin 1beta (IL-1beta), IL-8, IL-6 and tumor necrosis factor alpha (TNF-alpha) were measured both in SAT effluent and serum samples. Different time profiles were registered for each cytokine. IL-1beta increased in a time-dependent manner, indicating a localized response against the catheter insertion. Interleukin 1beta, 6 and 8 were higher in SAT than in serum suggesting they were locally produced. Diastolic blood pressure (DBP) negatively correlated with IL-1beta, IL 6 and IL-8 in SAT indicating a possible interaction between adipose tissue inflammation and vascular tone regulation. A multiple regression analysis disclosed that mean DBP was significantly related to IL-6 concentrations in SAT (B=-43.9; R-square=0.82; P=0.002). PMID- 20303783 TI - Prolonged stability of the plantibody HB-01 directed against the hepatitis B surface antigen in cryo-preserved tobacco leaves. AB - Since 1983, several recombinant antibodies have been expressed in important agronomic plant species. However, to date no evaluation has been published about prolonged antibody stability within plant tissues under cryo-preservation conditions. This current report presents an approach to the KDEL-plantibody HB-01 (PHB-01) stability in frozen tobacco leaves by presenting scientific evidence about the stability of a plantibody to a prolonged low temperature exposure in this biological source. Results clearly show that the PHB-01 amount is maintained during the storage of tobacco leaves at -20 degrees C for 90 days. The PHB-01 recovery was not affected by any irreversible physical and/or chemical change produced in tobacco leaves after this cryo-preservation time. The amount of total soluble proteins in the clarified extract decreased in proportion with the storage time and the PHB-01 molecules isolated from frozen leaf extracts were highly pure, >95%, according to an SDS-PAGE assessment under reducing conditions. Low temperature exposure of tobacco leaves did not reveal visible changes in frozen leaves, which is essential for the further extractability of proteins. The PHB-01 is stable in tobacco leaves at -20 degrees C during 90 days, which offers the possibility to overcome problems associated with detrimental climate conditions and optimize purification capabilities. PMID- 20303784 TI - Application of singular spectrum-based change-point analysis to EMG-onset detection. AB - While many approaches have been proposed to identify the signal onset in EMG recordings, there is no standardized method for performing this task. Here, we propose to use a change-point detection procedure based on singular spectrum analysis to determine the onset of EMG signals. This method is suitable for automated real-time implementation, can be applied directly to the raw signal, and does not require any prior knowledge of the EMG signal's properties. The algorithm proposed by Moskvina and Zhigljavsky (2003) was applied to EMG segments recorded from wrist and trunk muscles. Wrist EMG data was collected from 9 Parkinson's disease patients with and without tremor, while trunk EMG data was collected from 13 healthy able-bodied individuals. Along with the change-point detection analysis, two threshold-based onset detection methods were applied, as well as visual estimates of the EMG onset by trained practitioners. In the case of wrist EMG data without tremor, the change-point analysis showed comparable or superior frequency and quality of detection results, as compared to other automatic detection methods. In the case of wrist EMG data with tremor and trunk EMG data, performance suffered because other changes occurring in these signals caused larger changes in the detection statistic than the changes caused by the initial muscle activation, suggesting that additional criteria are needed to identify the onset from the detection statistic other than its magnitude alone. Once this issue is resolved, change-point detection should provide an effective EMG-onset detection method suitable for automated real-time implementation. PMID- 20303785 TI - Artificial nutritional support in chronic hemodialysis patients: a narrative review. AB - OBJECTIVE: Malnutrition is common in hemodialysis (HD) patients and is a powerful predictor of morbidity and mortality. While much progress has been made in identifying the causes and pathogenesis of malnutrition in patients on HD, no consensus has been reached on its management. Nutritional counseling, appetite stimulants, growth hormone, androgenic anabolic steroids, and anti-inflammatory drugs have been tested with contradictory and nonconclusive results. Oral nutritional supplements (ONSs) and intradialytic parenteral nutrition (IDPN) also have been studied. DESIGN/SETTING/PATIENTS: We searched the MEDLINE and PubMed databases for randomized clinical trials, comparative nonrandomized clinical trials, studies with patients who were controls for themselves, and single-arm studies on ONS and IDPN. Thirty-four studies (3223 patients) have been identified and analyzed. Seventeen studies were on ONS (778 patients) and 17 were on IDPN (2475 patients). RESULTS: ONS may improve serum albumin levels and/or other nutritional parameters, whereas there are insufficient data on clinical outcome. IDPN improves serum albumin and body weight. CONCLUSION: Data on survival are conflicting but the only study with an adequate population sample shows that IDPN does not influence survival. Randomized, controlled studies are needed to clarify the role of ONS and IDPN in the treatment of malnutrition in HD. PMID- 20303786 TI - Roles of calcium-sensing receptor and vitamin d receptor in the pathophysiology of secondary hyperparathyroidism. AB - The calcium-sensing receptor (CaR) and the vitamin D receptor (VDR) play key roles in calcium homeostasis. The CaR regulates the release of parathyroid hormone (PTH) in response to changes in extracellular calcium, whereas the VDR mediates the effects of calcitriol, the active metabolite of vitamin D. The development of secondary hyperparathyroidism (HPT) is a common complication of chronic kidney disease. Secondary HPT is characterized by disturbances in mineral metabolism, elevated serum PTH, and parathyroid gland hyperplasia. Alterations in CaR and VDR expression and activation play central roles in the development of secondary HPT. The impact of any nutritional and pharmacologic intervention on these two receptors should be carefully considered, to optimize patient outcomes. The important roles of CaR and VDR in the pathogenesis of secondary HPT are demonstrated by the complex interactions between their respective signaling pathways. PMID- 20303787 TI - Adherence to fish oil intervention in patients with chronic kidney disease. AB - OBJECTIVE: With growing recognition of the role of inflammation in the development of chronic and acute disease, fish oil is increasingly used as a therapeutic agent, but the nature of the intervention may pose barriers to adherence in clinical populations. Our objective was to investigate the feasibility of using a fish oil supplement in hemodialysis patients. DESIGN: This was a nonrandomized intervention study. SETTING: Eligible patients were recruited at the Hemodialysis Unit of Wesley Hospital, Brisbane, Queensland, Australia. PATIENTS: The sample included 28 maintenance hemodialysis patients out of 43 eligible patients in the unit. Exclusion criteria included patients regularly taking a fish oil supplement at baseline, receiving hemodialysis for less than 3 months, or being unable to give informed consent. INTERVENTION: Eicosapentaenoic acid (EPA) was administered at 2000 mg/day (4 capsules) for 12 weeks. Adherence was measured at baseline and weekly throughout the study according to changes in plasma EPA, and was further measured subjectively by self-report. RESULTS: Twenty patients (74%) adhered to the prescription based on changes in plasma EPA, whereas an additional two patients self-reported good adherence. There was a positive relationship between fish oil intake and change in plasma EPA. Most patients did not report problems with taking the fish oil. Using the baseline data, it was not possible to characterize adherent patients. CONCLUSIONS: Despite potential barriers, including the need to take a large number of prescribed medications already, 74% of hemodialysis patients adhered to the intervention. This study demonstrated the feasibility of using fish oil in a clinical population. PMID- 20303788 TI - Effects of omega-3 polyunsaturated fatty-acid supplementation on redox status in chronic renal failure patients with dyslipidemia. AB - OBJECTIVE: We sought to evaluate the effects of omega-3 polyunsaturated fatty acid (PUFA) supplementation on dyslipidemia, lipid and protein peroxidation, and antioxidant defense in patients with chronic renal failure (CRF). DESIGN: Eighty patients with CRF were diagnosed in the hospital of Oran between January 2008 and April 2008. Forty patients (male/female, 22/18; aged 61 +/- 14 years, S.D.) were available for the study. They presented with dyslipidemia and hypertriglyceridemia (triacylglycerols, >1.7 mmol/L) and/or hypercholesterolemia (total cholesterol, >5 mmol/L). INTERVENTION: All patients received nutritional counsel adapted to CRF, i.e., energy intake of .12 megajoule x kg(-1) x body weight x day(-1), protein intake of .8 g x kg(-1) x body weight x day(-1), and lipid intake of 35% of total energy intake with 28% PUFAs, 37% monounsaturated fatty acids, and 35% saturated fatty acids. Patients were randomized into two groups: 20 received supplementation with omega-3 fish oil (2.1 g . day(-1)) for 90 days, and 20 were used as controls. To control the counsel monitoring, a nutritional survey was performed at baseline and at 12 weeks. Blood samples were drawn at the beginning (T0), at 30 days (T1), at 60 days (T2), and at 90 days (T3) after initiating treatment. RESULTS: In the omega-3 group, a reduction in triacylglycerol levels was evident at T1 (-43%), T2, and T3 (-48%). Thiobarbituric acid-reactive substances were at lower levels at T1 and T3. There was no significant difference in carbonyl values, whereas serum superoxide dismutase and glutathione peroxidase activities were increased at T1, T2, and T3. High catalase activity was evident at T2 and T3. CONCLUSION: Omega-3 supplementation improves hypertriglyceridemia and oxidative stress in patients with CRF, and may lead to decreased rates of cardiovascular complications. PMID- 20303790 TI - The phase angle and mass body cell as markers of nutritional status in hemodialysis patients. AB - OBJECTIVE: Bioelectrical impedance analysis (BIA) is a fast, noninvasive method for assessing body composition, and its role in the evaluation of nutritional status in haemodialysis (HD) has been studied. This study aimed to compare BIA parameters to clinical, biochemical, and anthropometric markers of nutrition in HD patients, such as subjective global assessment modified for renal disease (SGA 1), serum albumin, body mass index (BMI), percent of standard body weight (%SBW), deviation of triceps skinfold thickness (TSF), mid-arm circumference (MAC), mid arm muscle circumference (MAMC) from the standard value (50th percentile), anthropometry-derived fat (FM-A), and fat-free mass (FFM-A). METHODS: BIA was performed 30 minutes after a HD session and the reactance (Xc), resistance (R), phase angle (PA), body cell mass (BCM), fat mass (FM-BIA), and fat-free mass (FFM BIA) values were recorded. The prevalence of malnutrition was estimated according to PA and percent of BCM. The correlation between methods was assessed through Pearson's correlation coefficient and Bland and Altman analysis. RESULTS: A total of 58 patients were studied (30 women and 28 men; mean age of 49.2 +/- 14.8 years). The mean PA was 6.19 +/- 1.33 degrees and the mean percent of BCM was 33.75 +/- 5.91%. The prevalence of malnutrition was 17.5% and 43.9% according to the PA and percent of BCM, respectively. PA had a negative correlation with age and SGA-1 score and a positive correlation with percent SBW, MAC, MAMC, FFM-A, and albumin. Percent of BCM had a negative correlation with age, MAC, MAMC and FM A and a positive correlation with FFM-A and albumin. A significant correlation between FFM-A and FFM-BIA was observed, as well as between FM-A and FM-BIA. CONCLUSIONS: BIA indexes reflected nutritional state. PA and BCM seem to be less influenced by changes in volume and can be used for nutritional assessments of dialysis patients. PMID- 20303789 TI - Folic acid supplementation and cardiac and stroke mortality among hemodialysis patients. AB - OBJECTIVE: We sought to assess whether the use of folic acid vitamin supplements reduced cardiac and stroke mortality in hemodialysis patients. Further, we examined whether the consumption of folic acid from vitamin supplements >1000 microg compared with the standard 1000 microg, and 1000 microg compared with either a lower dose or no consumption, were associated with reduced cardiac and stroke mortality risk. DESIGN: We performed a secondary analysis of data from the Hemodialysis Study, a randomized clinical trial examining dialysis treatment regimens over a 3-year follow-up. PARTICIPANTS: Participants included 1846 hemodialysis patients previously participating in the Hemodialysis Study. INTERVENTIONS: There were no interventions. MAIN OUTCOME MEASURE: Cardiac and stroke mortality were our main outcome measures. RESULTS: Based on time-dependent Cox proportional hazard regression models, folic acid consumption from vitamin supplements, above or below the standard 1000-microg dose, was not associated with a decrease or increase in cardiac mortality (P = .53, above vs. standard dose; P = .46, below vs. standard dose). There was also no association between folic acid consumption and mortality from stroke (P = .27, above vs. standard dose; P = .64, below vs. standard dose). CONCLUSION: The consumption of higher than the standard 1000-microg prescribed dose of folic acid was not beneficial in reducing cardiac or stroke mortality in hemodialysis patients. Similarly, the consumption of less than the standard dose was not associated with an increase in either cardiac or stroke mortality. PMID- 20303791 TI - Effect of intensified diet education on serum phosphorus and knowledge of pediatric peritoneal dialysis patients. AB - OBJECTIVE: To investigate the effect of intensive diet education on the knowledge and serum phosphorus levels of pediatric peritoneal dialysis (PD) patients and their parents. DESIGN: Interventional study using a pre-post design and convenience sample. SETTING: The study was performed in a pediatric PD clinic. PATIENTS: Sixteen patients ranging in age from 9 to 21 years and their parents. INTERVENTION: Patients routinely receive a review of laboratory results and a review of foods to limit. For the study, two additional education sessions were conducted. The additional phosphorus education to participants included a computer-based jeopardy game, handouts, education magnets and a hands-on learning activity. A 20 question before-and-after knowledge test was administered to the patients and parents separately. MAIN OUTCOME MEASURES: Change in serum phosphorus levels and the difference in pre and post knowledge test scores for both patients and parents. RESULTS: There was a significant increase in parent (p=0.003) and patient knowledge (p<0.001). There was a decrease in serum phosphorus from 2.3+/-0.68mmol/L to 2.16+/-0.58mmol/L (7.13+/-2.1mg/dL to 6.68+/ 1.8mg/dL), but this change was not statistically significant (p=0.256). CONCLUSION: Intensive education regarding phosphorus led to improved patient and family knowledge in pediatric PD patients. Although increased knowledge did not result in a significant decrease in serum phosphorus, there was a slight decrease indicating some clinical relevance. Therefore, pediatric PD patients may benefit from intensive on-going diet education sessions. PMID- 20303792 TI - Influence of purple grape juice in cyclosporine bioavailability. AB - OBJECTIVE: The present study was designed to investigate the effect of a single purple grape juice administration on cyclosporin A (CyA) oral bioavailability in healthy volunteers. DESIGN: The study followed a two-period crossover design, where the volunteers were randomly assigned to receive 200-mg CyA soft-gelatin capsules with 200 mL of either purple grape juice or water in the first day of the experiment. SETTING AND PATIENTS: Volunteers were kept at the clinical research unit during the blood sampling period and fasted from 10 p.m. until 4 hours after dosing. A washout period of 1 week was observed before the second treatment was administered. MAIN OUTCOME MEASURE: Blood samples were taken before and at 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, and 12 hours after CyA dosing. All meals received during the study day were standardized. Whole blood was assayed to determined CyA concentration using the Emit 2000 Cyclosporine specific immunoassay (Dade Behring Limited, Syva Company, Dade Behring Inc. Cupertino, CA). Pharmacokinetic parameters were determined by noncompartmental analysis from the individual whole blood concentration-time curves after each treatment using Excel 2003 software. Statistical analysis was performed using paired Student t test (a 5 .05) with the aid of SAS software. RESULTS: Twelve healthy male volunteers were enrolled in the study, with a mean age of 20.6 years (range 19 23 years). Purple grape juice significantly decreased cyclosporine AUC by 30% and Cmax by 28%. The time to peak blood level and elimination half-life of the drug, however, were not affected. The clearance determined increased around 50%, with purple grape juice. CyA half-life was not affected, indicating that the change observed in clearance (CL/F) was probably due to a change in the absorption (bioavailability) rather than in the elimination process after administration with purple grape juice. CONCLUSION: Purple grape juice decreased AUC and Cmax, whereas half-life was not changed, suggesting that juice affects the absorption and not drug elimination. The above findings are similar to previous data on the effects on CyA pharmacokinetics caused by the ingestion of red wine. Our findings are potentially relevant in the clinic. The intake of CyA with purple grape juice should be discouraged, as drug bioavailability can be decrease by 30%, leading to blood levels below the drug therapeutic window. A free interval of at least 2 hours between CyA intake and purple juice drinking is recommended. PMID- 20303793 TI - Gender, sexual orientation, and adolescent HIV testing: a qualitative analysis. AB - Using qualitative data, this article explored the circumstances leading to HIV testing among 59 HIV-infected adolescents recruited from New York City HIV clinics. Results showed differences between the heterosexual women and the gay and bisexual men. Most of the young women were tested during routine health care or self-initiated tests, and most were asymptomatic when they tested positive. Their testing decisions were sometimes based on assessments of their boyfriends' risk behaviors rather than their own. Many young men were experiencing symptoms of illness when they tested positive, and about half of them recognized their symptoms as related to HIV and sought tests. Some young men expressed fear of learning about positive test results, which delayed their testing, and some providers did not initially recommend HIV testing for young men who presented with symptoms. The article concludes that consideration of these gender and sexual orientation-related concerns can facilitate HIV testing among adolescents. PMID- 20303794 TI - Evaluation and pharmacologic management of the HIV-infected patient with dyslipidemia. AB - Dyslipidemia is common in persons living with HIV infection. Nurse clinicians must be able to recognize lipid abnormalities so that treatment plans can be developed. Managing dyslipidemia must be considered early in the HIV treatment process because certain antiretroviral therapy (ART) regimens, particularly those containing ritonavir, may exacerbate dyslipidemia risk. Statins are the most common medications used to treat dyslipidemia; however, because of drug-drug interactions, some are contraindicated with certain ART drugs. Other statins can be used but require dose adjustments when used with certain ART medications. Non statin medications such as fibrates, niacin, and omega-3 fatty acid (fish oil) can be used to manage lipids and are discussed. Nurse clinicians should be prepared to discuss with the health care team potential alternative drug regimens for concurrent treatment of HIV infection and dyslipidemia. PMID- 20303796 TI - Strengthening nurses' capacity to provide HIV care in China. PMID- 20303795 TI - Integrated care of an aging HIV-infected male-to-female transgender patient. PMID- 20303797 TI - A community-based program evaluation of community competency trainings. AB - Transgender and gender-nonconforming individuals encounter a multitude of barriers to accessing clinically and culturally competent health care. One strategy to increase the quality and competence of care delivery is workplace trainings. This study describes a community-based program for the evaluation of this type of training. Using a mixed-methods approach, the research team assessed the effectiveness of three competency trainings administered by a local nonprofit organization in the Northwest United States. Quantitative data indicated a significant shift in self-assessed knowledge associated with completion of the training. Qualitative data confirmed this result and revealed a number of important themes about the effect of the trainings on providers and their ability to implement knowledge and skills in practice. Clinical considerations are proposed for providers who seek similar trainings and who aim to increase clinical and cultural competency in delivering care to transgender and gender nonconforming patients and clients. PMID- 20303798 TI - Antiretroviral treatment and follow-up of HIV-infected patients by health care providers in South African public primary health care. AB - Antiretroviral therapy (ART) for HIV became available in the South African public health sector in 2004. Medical treatment in public primary health care (PHC) clinics is dependent on nurses and auxiliary staff. The aim of this descriptive study was to describe practice patterns and perceptions of health care providers (HCPs) regarding treatment of HIV-infected patients on ART, drug adherence, and patient education in a public PHC setting in the Eastern Cape, South Africa. Personal interviews, using a structured questionnaire, were conducted with all HCPs (N=43) working with the ART program at 7 PHC clinics. Insufficient training was expressed as a major concern. Medication adherence was believed to be the most important aspect of care to discuss with HIV-infected patients. HCPs perceived that patients had few side effects. HCPs faced challenges with heavy workloads, lack of sufficient human resources and training, and time constraints. PMID- 20303799 TI - Results of a new stemless shoulder prosthesis: radiologic proof of maintained fixation and stability after a minimum of three years' follow-up. AB - HYPOTHESIS: In total shoulder arthroplasty, the humeral component, particularly the stem, can be involved in some of the complications and technical difficulties increase in posttraumatic arthritis with proximal humeral malunion. To decrease the intraoperative complications related to the stem, the TESS (Biomet Inc, Warsaw, IN) humeral implant, was designed in 2004 hypothesis that we can obtain a good fixation with a stemless prosthesis. This investigation reports the preliminary results of this prosthesis with more than 3 years of follow-up. METHODS: Between March 2004 and June 2005, 70 patients underwent 72 shoulder replacements with the TESS humeral prosthesis. Sixty-three patients were reviewed with a follow-up of more than 36 months (average, 45.2 months; range, 36-51 months). The mean preoperative Constant score was 29.6. RESULTS: Gain in active mobility was 49 degrees for forward flexion and 20 degrees for external rotation. The postoperative Constant score was 75. Radiographic analysis showed no radiolucencies or implant migration. Functional results are comparable with previous reports on prosthetic glenohumeral replacement. DISCUSSION: Our clinical results are similar to this with classical prosthesis. The humeral head removal facilitates the glenoid exposure and implantation. After the initial cases any specific complication was seen. CONCLUSIONS: Owing to the automatic central positioning of the implant, an anatomic reconstruction was achieved. In malunions, no tuberosity osteotomy was required. At 3 years of follow-up, there is radiologic evidence of maintained implant stability. These encouraging preliminary results confirm our belief that a stemless prosthesis can be used to obtain an anatomic reconstruction of the proximal humerus. A longer-term follow up study is needed to validate these results. PMID- 20303800 TI - Electroencephalographic generalized features in idiopathic childhood focal epilepsies. AB - PURPOSE: Idiopathic focal epilepsies in childhood including benign childhood epilepsy with occipital paroxysms (BEOP) or benign childhood epilepsy with centro temporal spikes (BCECTS) are characterized by specific focal electrographic patterns as the name indicates. Generalized spike-wave discharges in children with idiopathic focal epilepsy can suggest a neurobiological continuum with the idiopathic generalized epilepsies. We assessed the prevalence of generalized epileptiform discharges and generalized seizures in BEOP/BCECTS patients. METHODS: Between August 2005 and November 2008, we identified 220 cases with electroclinical features typical of idiopathic focal epilepsies, 172 patients with BCECTS and 48 patients with BEOP, excluding patients whose neurological examinations or brain MRI were abnormal. We analyzed gender, age at onset, manifestation of generalized seizures, and serial EEG records to detect generalized abnormalities. RESULTS: Of our population, 42 patients (19.1%, 22 boys), 30 (17.4%) of 172 BCECTS patients and 12 (25.0%) of 48 BEOP patients, showed generalized spike-wave discharges once or more during follow-up. The typical 3-Hz generalized spike wave discharge was noticed in 7 patients and concurrence with clinical generalized seizure was observed in 11. CONCLUSION: A relatively high incidence of generalized spike-wave discharge and concurrence with generalized seizure were observed in patients with BEOP/BCECTS, with the incidence being higher in BEOP patients than in those with BCECTS. It may be inferred that idiopathic focal epilepsy is not a fixed syndrome but is a part of a broad, age-related, benign, seizure susceptibility syndrome. PMID- 20303801 TI - Prospective assessment of dorsal cheilectomy for hallux rigidus using a patient reported outcome score. AB - Compared with other surgical procedures for hallux rigidus, dorsal cheilectomy involves relatively less bone removal, maintains joint motion, and leaves the potential for further salvage surgery. The Manchester-Oxford Foot and Ankle Questionnaire (MOXFQ) has a maximum score of 64 (worst foot health) and has been endorsed by the British Foot and Ankle Society to measure surgical outcome. We prospectively assessed patient-reported outcomes after dorsal cheilectomy for hallux rigidus using the MOXFQ. Patients were deemed suitable for dorsal cheilectomy if they had painful restriction of terminal dorsiflexion, with absence of pain in the mid-range of passive movement, and radiographic evidence of dorsal osteophytosis. Twenty-five patients with a mean age of 62 years (range, 39-80 years), including 17 (68%) women, underwent dorsal cheilectomy for hallux rigidus. The mean preoperative MOXFQ score was 33.0 (95% confidence interval = 27.4-38.6), and, at a mean of 17 months (range, 9-27 months) follow-up, the mean postoperative score was 9.6 (95% confidence interval = 6.0-13.2). Eighty-four percent of patients experienced clinically significantly improved walking domain, 68% in the social domain, and 59% in the pain domain of the MOXFQ. Four patients failed cheilectomy, including 3 who subsequently underwent arthrodesis for persistent pain and 1 who experienced no improvement in any domain of the MOXFQ. This prospective study provided further evidence of the success of dorsal cheilectomy as a treatment for hallux rigidus and demonstrated the potential usefulness of the MOXFQ in assessing surgical outcomes in foot surgery. PMID- 20303802 TI - Evaluation of medical student experience using medical student created StudentPACS flash based PACS simulator tutorials for learning radiological topics. AB - RATIONALE AND OBJECTIVES: With studies regularly containing hundreds of images, the authors believe that the ability to efficiently review numerous images and identify findings is an important skill to teach medical students. Using the StudentPACS Adobe Flash extension, created within their department, the authors created StudentPACS modules that provide users with a virtual picture archiving and communication system environment, in which findings can be selected by mouse, triggering questions with referenced answers. The aim was to assess medical students' impressions of how learning from these modules compared to their personal experiences learning radiology from textbooks or static images. MATERIALS AND METHODS: StudentPACS modules were created by medical students on elective under the supervision of resident and attending radiologists. MS I to IV students were then asked to complete StudentPACS modules that tied in with their current coursework, followed by an anonymous survey. Approximately 293 students participated. RESULTS: The majority of students reported that StudentPACS modules were either equivalent to or better than learning from static images or textbooks (90 +/- 3% [257 of 285], P < .00002), were not difficult to use (85 +/- 4% [248 of 293], P < .00002), presented them with clinical content that tied in well with the depicted imaging (90 +/- 3% [263 of 293], P < .00002), and taught them new information (69 +/- 5% [202 of 293], P < .00002). Most respondents felt the StudentPACS modules presented information they would find useful in clinical practice (91 +/- 3% [266 of 293], P < .00002), reported satisfactory experiences using StudentPACS modules as a source of self-directed learning material (79 +/- 5% [232 of 293], P < .00002), and stated that they would use StudentPACS modules for learning different topics in the future (85.6 +/- 4% [244 of 285], P < .00002). CONCLUSION: Medical students found using StudentPACS modules at least equivalent to, if not better than, using static books or annotated images. PMID- 20303803 TI - Inflammatory response to aortic aneurysm intraluminal thrombus may cause increased 18F-FDG uptake at sites not associated with high wall stress: comment on "high levels of 18F-FDG uptake in aortic aneurysm wall are associated with high wall stress". PMID- 20303804 TI - Characteristics and outcome of patients hospitalised for lower extremity peripheral artery disease in France: the COPART Registry. AB - OBJECTIVES: To assess the current 'real-world' management of hospitalised patients with lower-extremity peripheral artery disease (LE-PAD) and to assess the 1-year outcome. DESIGN, MATERIALS AND METHODS: The prospective and multicentre registry COhorte des Patients ARTeriopathes (COPART) recruited consecutive patients from the departments of vascular medicine of three academic hospitals in Southwestern France. RESULTS: Among the 940 patients, 27.4% had intermittent claudication (IC), 9.3% ischaemic rest pain, 54.3% ulceration or gangrene and 9.3% acute limb ischaemia (ALI). Patients with IC were younger and more likely to be men, with a history of smoking (89.5%) and chronic obstructive pulmonary disease (17%). Among those with IC, 8.9% had bypass surgery and 41.5% were treated with percutaneous angioplasty. Those with tissue loss had higher rates of cardiovascular disease (CVD) risk factors and co-morbidities. At entry to the study, the level of control of the CVD risk factors was poor. The 1-year mortality rate was of 5.7% in patients with IC, 23.1% in patients with ischaemic rest pain, 28.7% in patients with tissue loss and 23% in those with ALI. Compliance with evidence-based medicine and pharmacological treatment was sub optimal. CONCLUSION: This registry underscores the differences in patient profiles in the daily clinical setting, compared to those enrolled in several trials. PMID- 20303805 TI - Review of direct anatomical open surgical management of atherosclerotic aorto iliac occlusive disease. AB - BACKGROUND: Aortofemoral bypass(AFB), iliofemoral bypass(IFB), and aortoiliac endarterectomy(AIE) are the three most common techniques for anatomical open surgical revascularisation for patients with aorto-iliac occlusive disease(AIOD), but the optimal method of reconstruction is unknown. AIMS: To review and compare mortality, morbidity and short- and long-term patency rates for AFB, IFB and AIE in patients with AIOD reported in the English language literature METHODS: A MEDLINE(1970-2007) and Cochrane Library search for articles relating to AFB, IFB, AIE and AIOD was undertaken. Studies were included if: a) patency rates based on life-tables were available, and b) patient/study characteristics were reported. RESULTS: 29 studies(5738 patients) for AFB, 11 studies(778 patients) for IFB and 11 studies(1490 patients) for AIE were included. Operative mortality was 4.1% for AFB, 2.7% for IFB and 2.7% for AIE (p<0.0001). Systemic morbidity was 16.0% for AFB, 18.9% for IFB and 12.5% for AIE (p<0.05). Overall 5-year primary patency rates were 86.3%, 85.3% and 88.3% for AFB, IFB and AIE, respectively (p=NS). CONCLUSION: Aorto-iliac endarterectomy was associated with significantly lower peri-operative morbidity and mortality rates compared with bypass grafting. All three techniques were equally effective in terms of long-term patency. PMID- 20303806 TI - A prospective evaluation of cerebral infarction following transcervical carotid stenting with carotid flow reversal. AB - OBJECTIVE: Cerebral embolisation constitutes the main source of complications during transfemoral carotid artery stenting (CAS) and is associated with a high incidence of silent brain infarction. The goal of this study is to evaluate the incidence of new ischaemic cerebral lesions following transcervical CAS with carotid flow reversal for neuroprotection. MATERIALS AND METHODS: Thirty-one consecutive patients underwent transcervical CAS with carotid flow reversal. A stroke scale and diffusion-weighted magnetic resonance imaging (DW-MRI) were performed within 24 h before and after the procedure. DW-MRI studies were compared blindly by two independent neuroradiologists. New hyper-intense DW signals were interpreted as ischaemic infarcts. The progress of all patients was followed for at least 30 days following intervention. RESULTS: All procedures were technically successful. Nineteen (61%) patients were symptomatic Mean carotid flow reversal time was 22 min. There were no major adverse events at 30 days. All patients remained neurologically intact without increase in the stroke scale. Thirty subjects had paired DW-MRI studies. Post-procedural DW-MRI ischaemic infarcts were found in four (12.5%) patients, all ipsilateral to the treated hemisphere and asymptomatic. During follow-up, all stents remained patent and all patients remained stroke-free. CONCLUSIONS: These data suggest that transcervical carotid stenting with carotid flow reversal carries a low incidence of new ischaemic infarcts, significantly lower than that reported with transfemoral CAS. The transcervical approach with carotid flow reversal may improve the safety of CAS and has the potential to produce results comparable to those of carotid endarterectomy. PMID- 20303807 TI - Cardinal series to filter oversampled truncated magnetic resonance signals. AB - Digital low pass filters are routinely used to improve the signal-to-noise ratio of NMR signals, e.g. FID or echoes, when pass band widths of the available analogue filters do not correspond to the spectral width of the signals. Applying digital filters will always necessitate an oversampling of the signal to filter. The digital filters with which the commercial spectrometers are nowadays equipped and most of those known to date from literature were designed to be applied to signals in the time domain. Nevertheless, most of them are aimed at optimising the filtering of signals in the frequency domain and tend to distort them in the time domain, especially when applied to truncated signals. Herein we propose a low pass filter that preserves all the features of the signal in both domains. The method consists in fitting raw NMR data with a finite sum of truncated cardinal sine functions and requires nothing but the signal being a band-limited function. We devised sensible and, in practice, hardly restrictive rules for setting parameters of the filter and applied it to various computer-simulated and experimentally measured truncated data sets to demonstrate its success in filtering both FID and echo signals. PMID- 20303808 TI - Application of mixed spin iMQCs for temperature and chemical-selective imaging. AB - The development of accurate and non-invasive temperature imaging techniques has a wide variety of applications in fields such as medicine, chemistry and materials science. Accurate detection of temperature both in phantoms and in vivo can be obtained using iMQCs (intermolecular multiple quantum coherences), as demonstrated in a recent paper. This paper describes the underlying theory of iMQC temperature detection, as well as extensions of that work allowing not only for imaging of absolute temperature but also for imaging of analyte concentrations through chemically-selective spin density imaging. PMID- 20303809 TI - Use of amplitude integrated electroencephalography (aEEG) in patients with inborn errors of metabolism - a new tool for the metabolic geneticist. AB - Patients with metabolic disorders often, especially as newborns, present with encephalopathy and seizures, frequently requiring intensive care during metabolic crises. Cerebral function monitoring using amplitude integrated electroencephalography (aEEG) can be utilized to supplement clinical assessment and other monitoring already in use in the intensive care setting. In this technique, a one or two-channel EEG tracing is obtained, processed, compressed and displayed. Use of aEEG is well established in evaluation and treatment of newborns with hypoxic ischemic encephalopathy. The basis of aEEG interpretation is the recognition of patterns which have been defined for different degrees of encephalopathy. Seizures are identified on the compressed tracing in combination with analysis of the corresponding raw EEG tracing. This review discusses the experience, although limited at this time, with use of aEEG in infants with inborn errors of metabolism. Through an international collaborative, the International Registry for Cerebral Function Monitoring in Patients with Genetics Disorders and Brain Malformations, aEEG tracings of patients with inborn errors of metabolism were collected. The features of 25 traces are included in this review. This collection includes patients with hyperammonemia (HA, n=4), disorders of energy metabolism (DEM, n=9), disorders of amino and organic acid metabolism (DAOAM, n=7), and peroxisomal disorders (PD, n=5). Fifteen of 25 patients demonstrated encephalopathic changes, including patients with HA, DEM and DAOAM, but not PD. In 15 of 25 patients seizure potentials were identified. In HA, DEM, and DAOAM both encephalopathy and seizures may coincide, while in peroxisomal disorders seizures were seen without background patterns indicating encephalopathy, likely due to neuronal migration defects as the underlying cause. The current experience with the use of aEEG in these patients, while limited, indicates that cerebral function monitoring techniques have a role in treatment of patients with metabolic disorders, especially during metabolic crises. Use of aEEG in this patient group is encouraged if locally available, and collaborative efforts to collect data on aEEG use in patients with metabolic disorders are encouraged to further define the scope and utility of this procedure. PMID- 20303811 TI - Silicone in HIV-1-infected patients: a cause of misdiagnosed granulomatous disease. AB - Granulomatous diseases are common in HIV-infected patients and are usually related to opportunistic infectious or tumoral conditions. We report three cases of uncommon granulomatous disease in HIV-infected patients who had previously received silicone and for which diagnostic investigations remained negative. PMID- 20303810 TI - N-acetylglutamate synthase: structure, function and defects. AB - N-acetylglutamate (NAG) is a unique enzyme cofactor, essential for liver ureagenesis in mammals while it is the first committed substrate for de novo arginine biosynthesis in microorganisms and plants. The enzyme that produces NAG from glutamate and CoA, NAG synthase (NAGS), is allosterically inhibited by arginine in microorganisms and plants and activated in mammals. This transition of the allosteric effect occurred when tetrapods moved from sea to land. The first mammalian NAGS gene (from mouse) was cloned in 2002 and revealed significant differences from the NAGS ortholog in microorganisms. Almost all NAGS genes possess a C-terminus transferase domain in which the catalytic activity resides and an N-terminus kinase domain where arginine binds. The three dimensional structure of NAGS shows two distinctly folded domains. The kinase domain binds arginine while the acetyltransferase domain contains the catalytic site. NAGS deficiency in humans leads to hyperammonemia and can be primary, due to mutations in the NAGS gene or secondary due to other mitochondrial aberrations that interfere with the normal function of the same enzyme. For either condition, N-carbamylglutamate (NCG), a stable functional analog of NAG, was found to either restore or improve the deficient urea-cycle function. PMID- 20303812 TI - Lipogenesis in arterial wall and vascular smooth muscle cells of Psammomys obesus: its regulation and abnormalities in diabetes. AB - AIM: Lipogenesis is expressed in vascular smooth muscle cells (VSMCs), and such in situ lipogenesis could be providing the fatty acids for triglyceride synthesis and cholesterol esterification, and contributing to lipid accumulation in the arterial wall. This study investigated both the expression and regulation of lipogenesis in VSMCs to determine if they are modified in Psammomys obesus gerbils fed a high-fat diet as a model of insulin resistance and diabetes. METHODS: Aortas were collected from diabetic and non-diabetic P. obesus for histological examination, measurement of lipogenic gene expression and VSMC culture. RESULTS: The aortas of diabetic animals exhibited lipid deposits and foam cells as well as disorganization of elastic fibres. However, lipogenic gene expression was not modified. VSMCs in vitro from the aortas of diabetic animals had, compared with cells from non-diabetic animals, lower mRNA levels of SREBP-1c and ChREBP. An adipogenic medium stimulated moderate FAS and ACC1 expression in cells from both diabetic and non-diabetic animals, but glucose and insulin on their own had no such stimulatory action. Also, triiodothyronine (T3) had a clear stimulatory action, while angiotensin II had a moderate effect, in cells from non diabetic P. obesus, but not from diabetic animals, whereas LXR agonists stimulated lipogenesis in cells from both animal groups. CONCLUSION: Lipogenesis is expressed in the arterial walls and VSMCs of P. obesus. However, its expression was not increased in diabetes, and did not respond to either T3 or angiotensin II. Therefore, lipogenesis in situ is unlikely to contribute to the accumulation of lipids in the arterial walls of diabetic P. obesus gerbils. PMID- 20303813 TI - Reproducibility of HOMA and QUICKI among individuals with variable glucose tolerance. PMID- 20303814 TI - Sexual activity in diabetic patients treated by continuous subcutaneous insulin infusion therapy. AB - BACKGROUND AND AIMS: As concerns over interference with sexual activity may be an obstacle to initiating pump therapy in diabetic patients, the aim of the study was to assess the impact of continuous subcutaneous insulin infusion (CSII) therapy on sexual activity. PATIENTS AND METHODS: Patients filled out a questionnaire on their demographic data, diabetes history, pump-treatment history, metabolic control, inconvenience/convenience of the pump and catheter, and information on sexual activity. RESULTS: A total of 271 diabetic patients (aged 44+/-17 years, 51% women, 22% single), treated with CSII for 4.2+/-5.9 years and with a diabetes duration of 19+/-11 years, filled out the questionnaire. Their HbA(1c) was 7.7+/-1.1%, with 2.4+/-2.1 mild hypoglycaemic episodes over the past week, and their frequency of sexual activity was: never 29.9%; <1/month 12.3%; >1/month and <1/week 18.2%; and >1/week 39.6%. Age and cohabitation were independently correlated with frequency of sexual activity (P<0.0001 and P<0.0003, respectively), but not diabetes duration or complications. To the question "Does the pump have an influence on your sexual activity?", The answer was "no" in 90% and "yes" in 10%. However, intercourse frequency was significantly decreased in the latter (P=0.04). On multivariate analyses, this negative influence of CSII was correlated with HbA(1c) (P<0.05), discomfort with the pump (P<0.05) and the number of mild hypoglycaemic episodes (P<0.01). CONCLUSION: Frequency of sexual activity appears to be unaffected by pump therapy or diabetes, but is decreased by the expected characteristics namely, age and being single. Also, only 10% of patients believe that CSII is an obstacle during sexual activity and, in particular, because of the catheter. PMID- 20303815 TI - Glucose flux in controlled hyperglycaemia before and after oral glucose ingestion in men with mild type 2 diabetes. AB - AIMS: This study aimed to determine how insufficiently suppressed endogenous glucose production vs. reduced peripheral glucose uptake contribute to postprandial hyperglycaemia in type 2 diabetes (T2D). METHODS: Eight men with T2D (age: 52+/-7 years; BMI: 26.6+/-2.3 kg/m(2); fasting glycaemia: 7.1+/-1.5 mmol/L) were compared with eight non-diabetic controls (age: 51+/-5 years; BMI: 24.6+/ 2.9 kg/m(2); fasting glycaemia: 4.9+/-0.4 mmol/L). Their glucose turnover rates and hepatic glucose cycles were measured by monitoring [2H7]glucose infusion, with m+7 and m+6 enrichment, 3 h before and 4 h after the ingestion of [6,6-2H2] labelled glucose, while maintaining glycaemia at 10 mmol/L using the pancreatic clamp technique. RESULTS: Of the 700 mg/kg oral glucose load, 71% appeared in the systemic circulation of the T2D patients vs. 63% in the controls (NS). Endogenous glucose production and hepatic glucose cycles did not differ from normal either before or after oral glucose ingestion, while peripheral glucose uptake was reduced by 40% in the T2D group both before (P<0.01) and after (P<0.05) ingestion of oral glucose. CONCLUSION: When T2D patients were compared with non-diabetic subjects with similarly controlled levels of hyperglycaemia after oral glucose ingestion, they essentially differed only in peripheral glucose uptake, whereas endogenous glucose production was apparently unaltered. PMID- 20303816 TI - [Joseph-Guichard Duverney (1648-1730). Doctor, teacher and researcher in the 17th and 18th centuries]. AB - Duverney was a leader in the field of research and education, because he worked as a physician, as a surgeon and he led many scientific works. To Peltier, he was the first academic professor of surgery. His wonderful career was explained by his heavy interest in knowledge. He became one of the main actors of the scientific revolution of the 17th century, especially concerning the methods of investigation in the medical science. He had so much fear for imperfect purposes, that many scientists of his century called him the Master. The only work he published about the anatomy and physiology of the ear and audition, was a world success, and is still amazing today. During about 50 years, Duverney allowed many advances in the field of osteology, otology, embryology, respiratory and circulatory physiology, but also provided competent pupils as Winslow, Senac, Petit, Dionis, Valsalva. Duverney is still frequently cited by veterinary and dentists for many descriptions in animal anatomy. He died at the age of 82 years, and worked for the service of science until his death. His legacy consists of many works, some have been used by his pupils to highlight all the benefits he gave to the scientific community. PMID- 20303817 TI - Genetic variation analysis of 15 autosomal STR loci of AmpFlSTR Sinofiler PCR Amplification Kit in Henan (central China) Han population. AB - AmpFlSTR Sinofiler PCR Amplification Kit is specially developed for Chinese forensic laboratories, but there are little population-genetic indices about this kit as a whole. This kit contains 15 STR loci: D8S1179, D21S11, D7S820, CSF1PO, D3S1358, D13S317, D16S539, D2S1338, D19S433, vWA, D18S51, D6S1043, D12S391, D5S818 and FGA. In order to evaluate this kit and to get basic population-genetic indices for its use in forensic practice in Chinese Han population, the DNA of 231 unrelated Han individuals from Henan (central China) were typed using the Kit. The most discriminating locus was D6S1043 while the least was D3S1358. The combined match probability was 9.81x10(-19) and the combined power of exclusion was 0.99999974. Statistical analysis of the generated data indicated no departure from expectation of Hardy-Weinberg Equilibrium (HWE) in all loci but D6S1043 and no linkage disequilibrium in all pairs of loci. The observed and expected heterozygosity, power of discrimination, polymorphic information content, the other population-genetic indices were calculated. PMID- 20303818 TI - Death due to blood transfusion-induced anaphylactic shock: A case report. AB - In medical practice, many clinical accidents due to blood transfusion reactions have been reported, among which, nonhemolytic transfusion reactions (NHTRs) have been mainly reported in recent years. NHTRs induce reactions such as anaphylactic shock and transfusion-related acute lung injury (TRALI); however, few forensic autopsy case reports with blood transfusion reactions including anaphylactic shock have been published. A marker for anaphylactic shock is serum tryptase, which indicates systematic mast cell activation in living patients. In forensic medicine, serum tryptase has been used in the postmortem diagnosis of anaphylactic shock. In this autopsy case report, the blood tryptase level was elevated to 49.0 ng/mL (reference standard level <13.5 ng/mL). When considered comprehensively with autopsy findings and blood typing, we concluded that this patient was suspected to have suffered from anaphylactic shock as a result of blood transfusion. PMID- 20303819 TI - Sonolytic degradation of parathion and the formation of byproducts. AB - Ultrasonic degradation of parathion has been investigated in this study. At a neutral condition, 99.7% of 2.9 microM parathion could be decomposed within 30 min under 600 kHz ultrasonic irradiation at ultrasonic intensity of 0.69 W/cm(2). The degradation rate increased proportionally with the increasing ultrasonic intensity from 0.10 to 0.69 W/cm(2). The parathion degradation was enhanced in the presence of dissolved oxygen due to formation of more ()OH, but was inhibited in the presence of nitrogen gas owning to the free radical scavenging effect in vapor phase within the cavitational bubbles. CO(3)(2-), HCO(3)(-), and Cl(-) exhibited the inhibiting effects on parathion degradation, and their inhibition degrees followed the order of CO(3)(2-)>HCO(3)(-)>Cl(-). But Br(-) had a promoting effect on parathion degradation, and the effect increased with the increasing Br(-) level. Moreover, both the hydrophobic and hydrophilic natural organic matters (NOM) could slow the parathion degradation, but the inhibiting effect caused by hydrophobic component was greater, especially the strongly hydrophobic NOM. The three reaction pathways of parathion sonolysis were proposed, including formation of paraoxon, formation of 4-nitrophenol, and unknown species products. The kinetics tests showed that anyone of these pathways could not be overlooked, and the fractions of the parathion decomposed in the three pathways were 28.19%, 32.92% and 38.89%, respectively. In addition, 66.61% of paraoxon produced was degraded into 4-nitrophenol. Finally, kinetics models were established to adequately predict the concentrations of parathion, paraoxon and 4-nitrophenol as a function of time. PMID- 20303820 TI - Source to sink: regulation of carotenoid biosynthesis in plants. AB - Carotenoids are a diverse group of colourful pigments naturally found in plants, algae, fungi and bacteria. They play essential roles in development, photosynthesis, root-mycorrhizal interactions and the production of phytohormones, such as abscisic acid and strigolactone. Carotenoid biosynthesis is regulated throughout the life cycle of a plant with dynamic changes in composition matched to prevailing developmental requirements and in response to external environmental stimuli. There are key regulatory nodes in the pathway that control the flux of metabolites into the pathway and alter flux through the pathway. The molecular nature of the mechanisms regulating carotenoid biosynthesis, including evidence for metabolite feedback, transcription and epigenetic control as well as their accumulation, storage and degradation will be the focus of this review. PMID- 20303821 TI - Biosynthesis of glucosinolates--gene discovery and beyond. AB - Glucosinolates are sulfur-rich secondary metabolites characteristic of the Brassicales order with important biological and economic roles in plant defense and human nutrition. Application of systems biology tools continues to identify genes involved in the biosynthesis of glucosinolates. Recent progress includes genes in all three phases of the pathway, i.e. side-chain elongation of precursor amino acids, formation of the core glucosinolate structure and side-chain decoration. Major breakthroughs include the ability to produce glucosinolates in Nicotiana benthamiana, the finding that specific glucosinolates play a key role in Arabidopsis innate immune response, and a better understanding of the link between primary sulfur metabolism and glucosinolate biosynthesis. PMID- 20303822 TI - Future turnovers in enzyme catalysis. PMID- 20303823 TI - Engineering of regulatory cascades and networks controlling antibiotic biosynthesis in Streptomyces. AB - Engineering of regulatory mechanisms that control the biosynthesis of bioactive secondary metabolites is an approach to increase the production of valuable fermentation products. Two types of regulatory mechanisms have been studied in Streptomyces species: (1) pyramidal cascades of regulation that usually involve a butyrolactone and its receptor protein triggering the formation of pathway associated regulatory proteins (SARP), and (2) global regulators that transduce protein phosphorylation signals responding to stress factors. Global regulators are frequently two-component systems; for example, the PhoR-PhoP system, the AsbA1-AsbA2, the orphan response regulator GlnR and the STAND-family regulator AfsR. Several strategies have been used to obtain overproducer strains, including: (i) obtention of phosphate-deregulated mutants by alteration of phoP, (ii) amplification and/or overexpression of pathway-associated positive regulators, and (iii) modification of butyrolactone receptor proteins. The success of these strategies is hampered by the poor knowledge of interactions between regulatory mechanisms. PMID- 20303824 TI - Effect of temperature and quencher on the fluorescence of 4-(5-methyl-3-furan-2 yl-benzofuran-2-yl)-7-methyl-chromen-2-one in different solvents. AB - The effect of temperature on the fluorescence intensity of 4-(5-methyl-3-furan-2 yl-benzofuran-2-yl)-7-methyl-chromen-2-one (MFBMC) in different solvents, has been studied in the temperature range 293-333K. A mechanism of fluorescence quenching with increase in temperature is discussed in terms of the relative location of lowest (1)(pipi*) and (3)(npi*) states, and the energy difference between them. The non-radiative deactivation of excited state in the absence of quencher is temperature-dependent; its activation energy has been found to be 9.453-27.893kJmole(-1). Further, the fluorescence quenching by aniline was investigated by both steady-state and time-resolved measurement (at 296K). The quenching is found to be appreciable and shows positive deviation in the Stern Volmer plots. This could be explained by static-dynamic quenching models. Various rate constants of the bimolecular quenching reaction have been determined by using ground-state complex formation and sphere of action static quenching model. The magnitude of these constants suggests that sphere of action static quenching model agrees very well with experimental results. Further, with the use of finite sink approximation model, it is concluded that the quenching mechanism is diffusion-limited. PMID- 20303825 TI - Characterisation of multidrug-resistant Salmonella Typhimurium 4,[5],12:i:- DT193 strains carrying a novel genomic island adjacent to the thrW tRNA locus. AB - In 2006, monophasic, multidrug-resistant Salmonella enterica spp. enterica serovar 4,[5],12:i:- strains appeared as a novel serotype in Germany, associated with large diffuse outbreaks and increased need for hospitalisation. The emerging 4,[5],12:i:- strains isolated from patients in Germany belong mainly to phage type DT193 according to the Anderson phage typing scheme for S. Typhimurium (STM) and exhibit at least a tetra-drug resistance. The strains have been shown to harbour STM-specific Gifsy-1, Gifsy-2, and ST64B prophages. Furthermore, the extensive sequence similarity of the tRNA regions between one characterised 4,[5],12:i:- phage type DT193 and the S. Typhimurium LT2 strain as well as the STM-specific position of an IS200 element within the fliA-fliB intergenic region (Echeita et al., 2001) prompted us to classify them as a monophasic variant of S. Typhimurium. In 2008, the monophasic variant represented 42.2% of all S. Typhimurium isolates from human analysed at the National Reference Centre. Searching for insertions in tRNA sites resulted in the detection of an 18.4-kb fragment adjacent to the thrW tRNA locus, exhibiting a lower G+C content compared to the LT2 genome. Sequence analysis identified 17 potential ORFs. Some of them showed high similarity to enterobacterial phage sequences and sequences from Shigella boydii, Sh. dysenteriae, avian pathogenic Escherichia coli and other Escherichia spp. The biological function of this novel island with respect to virulence properties and metabolic functions is under investigation. PMID- 20303827 TI - Overweight among low-income Texas preschoolers aged 2 to 4 years. AB - OBJECTIVE: Determine child/maternal factors associated with overweight among 2- to 4-year-olds enrolled in the Texas Special Supplemental Nutrition Program for Women, Infants, and Children (WIC). DESIGN: Matched child and maternal data collected by self-report of the mother during WIC certification. These data were extracted from existing statewide WIC databases and merged. SETTING: Texas WIC children aged 2 to 4 years in April 2006. PARTICIPANTS: Final sample was 22,837 mother-child dyads. MAIN OUTCOME MEASURE: Dependent variable--child overweight; independent variables: Child-related--gender, age, race/ethnicity, Medicaid status, living area, and dental problems; Maternal-related--certification status, age, times certified, overweight, high maternal weight gain, and gestational diabetes. ANALYSIS: Bivariate relationships at P < .05 were included in the logistic regression. RESULTS: Living in a nonborder urban area associated with greater odds of overweight compared to living in a border area. Mother's overweight, high gestational weight gain, and gestational diabetes associated with greater odds of child overweight. CONCLUSIONS AND IMPLICATIONS: Several child- and maternal-related factors were found to be associated with overweight in Texas WIC preschoolers. Health interventions should target 4-year-old Hispanic children living in nonborder urban areas and mothers who are overweight, have high gestational weight gain, or have gestational diabetes. PMID- 20303826 TI - Regenerative medicine for retinal diseases: activating endogenous repair mechanisms. AB - The retina is subject to degenerative diseases that often lead to significant visual impairment. Non-mammalian vertebrates have the remarkable ability to replace neurons lost through damage. Fish, and to a limited extent birds, replace lost neurons by the dedifferentiation of Muller glia to a progenitor state followed by the replication of these neuronal progenitor cells. Over the past five years, studies have investigated whether regeneration can be stimulated in the mouse and rat retina. Several groups have reported that at least some types of neurons can be regenerated in the mammalian retina in vivo or in vitro, and that the regeneration of neurons can be stimulated using growth factors, transcription factors or subtoxic levels of excitatory amino acids. These recent results suggest that some part of the regenerative program that occurs in non mammalian vertebrates remains in the mammalian retina, and could provide a basis to develop new strategies for retinal repair in patients with retinal degenerations. PMID- 20303828 TI - Perceptions of the environment for eating and exercise in a rural community. AB - OBJECTIVE: To understand how members of a rural community perceive the effect of the built, natural, and social environments on their food choice and physical activity behaviors. METHODS: A constructivist community environmental assessment was conducted including 17 individual qualitative interviews, 2 focus groups, and photo elicitation (n = 27) in a rural northeastern community where over 60% of the adult population is overweight or obese. RESULTS: Participants described social, natural, and physical environmental factors that influenced their food choice and physical activity behaviors. Overweight and obesity were variably presented as an individual and/or a collective problem. Participants described conflicting goals for food choice and physical activity in the community, and an interrelationship between the social and physical environments. CONCLUSIONS AND IMPLICATIONS: A community environmental assessment provides a view of the physical and social environments from the perspective of community residents that can serve as a foundation for locally tailored, community-based approaches to obesity prevention. PMID- 20303829 TI - Abortion among young women and subsequent life outcomes. AB - This article will discuss the nature of the association between abortion and mental health problems. Studies arguing about both sides of the debate as to whether abortion per se is responsible will be presented. The prevalence of various psychiatric disorders will be outlined and where there is dispute between studies, these will be highlighted. The impact of abortion on other areas such as education, partner relationships and sexual function will also be considered. The absence of specific interventions will be highlighted. Suggestions for early identification of illness will be made. PMID- 20303830 TI - Abortion and human rights. AB - Abortion has been a reality in women's lives since the beginning of recorded history, typically with a high risk of fatal consequences, until the last century when evolutions in the field of medicine, including techniques of safe abortion and effective methods of family planning, could have ended the need to seek unsafe abortion. The context of women's lives globally is an important but often ignored variable, increasingly recognised in evolving human rights especially related to gender and reproduction. International and regional human rights instruments are being invoked where national laws result in violations of human rights such as health and life. The individual right to conscientious objection must be respected and better understood, and is not absolute. Health professional organisations have a role to play in clarifying responsibilities consistent with national laws and respecting reproductive rights. Seeking common ground using evidence rather than polarised opinion can assist the future focus. PMID- 20303831 TI - Induced abortion and psychological sequelae. AB - The decision to seek an abortion is never easy. Women have different reasons for choosing an abortion and their social, economic and religious background may influence how they cope. Furthermore, once pregnant, the alternatives of childbirth and adoption or keeping the baby may not be psychologically neutral. Research studies in this area have been hampered by methodological problems, but most of the better-quality studies have shown no increased risk of mental health problems in women having an abortion. A consistent finding has been that of pre existing mental illness and subsequent mental health problems after either abortion or childbirth. Furthermore, studies have shown that only a minority of women experience any lasting sadness or regret. Risk factors for this include ambivalence about the decision, level of social support and whether or not the pregnancy was originally intended. More robust, definitive research studies are required on mental health after abortion and alternative outcomes such as childbirth. PMID- 20303832 TI - Strategy for laparoscopic cervical myomectomy. AB - OBJECTIVE: Myoma of the uterine cervix is rare, accounting for about 5% of all myomas. Compared with myomas that occur in the uterine corpus, cervical myomas are closer to other organs such as the bladder, ureter, and rectum, and the approach needs to be modified because the organs that have to be considered differ depending on the location of the myoma. We divided cervical myomas into 2 types according to location, comprising an intracervical type and extracervical types. A clear outline of surgical treatment for cervical myoma has not described in previous papers. We then investigated the surgical strategy for these types. PATIENTS: Subjects comprised 16 patients who were diagnosed with cervical myoma in our hospital between January 2005 and April 2009, and who underwent laparoscopic myomectomy. RESULT: Mean operative time was 105.8 + or - 43.2 (82.8 128.8) min, mean blood loss was 105 + or - 117 (42.6-167.4) ml, and mean specimen weight was 208.3 + or - 195.4 (99.3-306.2) g. Histopathological examination showed atypical myoma in 1 case and leiomyoma in others. CONCLUSIONS: 16 cases of cervical myomectomy were performed safely by developing a uniform strategy that uses a fixed operative procedure, even with laparotomy, if sufficient attention is paid to the following 6 points: 1) attempting to reduce the size of the myoma with the use of preoperative GnRH; 2) determining the positional relationship between the myoma and surrounding organs; 3) temporarily blocking uterine artery blood flow with the use of vessel clips; 4) suppressing bleeding during myomectomy with the use of vasopressin; 5) minimizing the risk of damaging surrounding organs by positioning the incision in the myometrium somewhat lateral to the uterine corpus; and 6) the bottom of the wound after enculation should be pulled up by the forceps for suturing to avoid making dead space. PMID- 20303833 TI - Pressure-controlled vs volume-controlled ventilation during laparoscopic gynecologic surgery. AB - STUDY OBJECTIVE: To quantify and compare the effects of conventional volume controlled ventilation (VCV) with the alternative mode, pressure-controlled ventilation (PCV), on respiratory mechanics and noninvasive hemodynamic parameters in patients undergoing laparoscopic gynecologic surgery. DESIGN: Randomized controlled trial (Canadian Task Force classification I). SETTING: Respiratory mechanics and hemodynamic parameters were recorded for each patient at time T1, 10 minutes after induction, in the supine position; T2, 15 minutes after pneumoperitoneum, in the Trendelenburg position; and T3, 10 minutes after pneumoperitoneum withdrawal, in the supine position. PATIENTS: Sixty women, aged 20 to 50 years, undergoing laparoscopic gynecologic surgery, with American Society of Anesthesiologists classes I and II disease. INTERVENTIONS: Patients were randomly allocated to 1 of 2 groups. In the VCV group (n = 30), ventilation mode was maintained, whereas in the PCV group (n = 30), ventilation mode was changed to PVC. MEASUREMENTS AND MAIN RESULTS: Both groups were comparable insofar as patient characteristics, operating time, pneumoperitoneum time, anesthesia time, and mean operative time. VCV was associated with a significant increase in peak airway pressure, plateau pressure, and airway resistance at T2 (p < .05). Compliance was significantly higher in the PCV group at T2 (p < .05). No other statistically significant differences were found between the groups. CONCLUSIONS: Both VCV and PCV seem to be equally suited for use in patients undergoing laparoscopic gynecologic surgery. However, lower peak airway pressure, plateau pressure, and airway resistance, and higher compliance are observed with PCV in laparoscopic gynecologic surgery. PMID- 20303834 TI - Robot-assisted laparoscopic myomectomy is an improvement over laparotomy in women with a limited number of myomas. AB - STUDY OBJECTIVE: To compare surgical and immediate postoperative results of robot assisted laparoscopic myomectomy vs myomectomy via laparotomy in patients with 3 myomas or fewer. DESIGN: Case-control (Canadian Task Force classification II-2). SETTING: University hospital. PATIENTS: Seventy-five women who had undergone robotic-assisted laparoscopic myomectomy were compared with patients who had undergone myomectomy via laparotomy. INTERVENTIONS: Medical records were reviewed for surgical and postoperative variables. Both groups had 3 myomas or fewer confirmed at preoperative magnetic resonance imaging or final pathology report. MEASUREMENTS AND MAIN RESULTS: No significant differences were observed between patients insofar as preoperative demographic data. There was a significant increase in mean duration of surgery for robotic-assisted myomectomy. There was a significant decrease in blood loss, change in hematocrit concentration on postoperative day 1, length of stay, number of days to regular diet, and febrile morbidity in robotic-assisted myomectomies. There were no significant differences in operative or postoperative complications. CONCLUSION: Although robotic assisted myomectomy took substantially longer, most of the other variables improved in comparison with similar procedures performed via laparotomy. PMID- 20303835 TI - p21CDKN1A participates in base excision repair by regulating the activity of poly(ADP-ribose) polymerase-1. AB - The cell cycle inhibitor p21(CDKN1A) has been shown to participate in nucleotide excision repair by interacting with PCNA. Here we have investigated whether p21 plays a role in base excision repair (BER), by analyzing p21 interactions with BER factors, and by assessing the response of p21(-/-) human fibroblasts to DNA damage induced by alkylating agents. Absence of p21 protein resulted in a higher sensitivity to alkylation-induced DNA damage, as indicated by reduced clonogenic efficiency, defective DNA repair (assessed by the comet test), and by persistence of histone H2AX phosphorylation. To elucidate the mechanisms at the basis of the function of p21 in BER, we focused on its interaction with poly(ADP-ribose) polymerase-1 (PARP-1), an important player in this repair process. p21 was found to bind the automodification/DNA binding domain of PARP-1, although some interaction occurred also with the catalytic domain after DNA damage. This association was necessary to regulate PARP-1 activity since poly(ADP ribosylation) induced by DNA damage was higher in p21(-/-) human fibroblasts than in parental p21(+/+) cells, and in primary fibroblasts after p21 knock-down by RNA interference. Concomitantly, recruitment of PARP-1 and PCNA to damaged DNA was greater in p21(-/-) than in p21(+/+) fibroblasts. This accumulation resulted in persistent interaction of PARP-1 with BER factors, such as XRCC1 and DNA polymerase beta, suggesting that prolonged association reduced the DNA repair efficiency. These results indicate that p21 regulates the interaction between PARP-1 and BER factors, to promote efficient DNA repair. PMID- 20303836 TI - Online solid phase extraction with liquid chromatography-tandem mass spectrometry to analyze remoxipride in small plasma-, brain homogenate-, and brain microdialysate samples. AB - Remoxipride is a selective dopamine D(2) receptor antagonist, and useful as a model compound in mechanism-based pharmacological investigations. To that end, studies in small animals with serial sampling over time are needed. For these small volume samples currently no suitable analytical methods are available. We propose analytical methods for the detection of low concentrations remoxipride in small sample volumes of plasma, brain homogenate, and brain microdialysate, using online solid phase extraction with liquid chromatography-tandem mass spectrometry. Method development, optimization and validation are described in terms of calibration curves, extraction yield, lower limit of quantification (LLOQ), precision, accuracy, inter-day- and intra-day variability. The 20 microl plasma samples showed an extraction yield of 76%, with a LLOQ of 0.5 ng/ml. For 0.6 ml brain homogenate samples the extraction yield was 45%, with a LLOQ of 1.8 ng/ml. The 20 microl brain microdialysate samples, without pre-treatment, had a LLOQ of 0.25 ng/ml. The precision and accuracy were well within the acceptable 15% range. Considering the small sample volumes, the high sensitivity and good reproducibility, the analytical methods are suitable for analyzing small sample volumes with low remoxipride concentrations. PMID- 20303837 TI - [Soluble intercellular adhesion molecule-1 and C reactive protein after bariatric surgery]. AB - BACKGROUND AND OBJECTIVES: Obesity is associated with a state of chronic low grade inflammation. A causal association between inflammatory processes and atherogenesis has been proposed. The aim of this study was to evaluate changes in the proinflammatory profile of morbidly obese patients who underwent bariatric surgery. Serum C-reactive protein (CRP) and soluble intercellular adhesion molecule-1 (sICAM-1) concentrations were measured before and after massive weight loss due to gastric bypass. METHODS: In this prospective study we measured CRP and sICAM-1 concentrations in 50 morbidly obese patients (19 men and 31 women) at baseline and 3, 6 and 12 months after gastric bypass. RESULTS: Body mass index (BMI), CRP, and sICAM-1 decreased significantly. BMI correlated with CRP but not with sICAM-1. CONCLUSIONS: The improvement in vascular risk profile after weight loss in morbidly obese patients could be partially explained by changes in inflammatory status. PMID- 20303839 TI - Colorectal cancer screening: dying en route? PMID- 20303838 TI - Taurocholic acid prevents biliary damage induced by hepatic artery ligation in cholestatic rats. AB - BACKGROUND: Ischemic injury by hepatic artery ligation (HAL) during obstructive cholestasis induced by bile duct ligation (BDL) results in bile duct damage, which can be prevented by administration of VEGF-A. The potential regulation of VEGF and VEGF receptor expression and secretion by bile acids in BDL with HAL is unknown. AIMS: We evaluated whether taurocholic acid (TC) can prevent HAL-induced cholangiocyte damage via the alteration of VEGFR-2 and/or VEGF-A expression. METHODS: Utilizing BDL, BDL+TC, BDL+HAL, BDL+HAL+TC, and BDL+HAL+wortmannin+TC treated rats, we evaluated cholangiocyte apoptosis, proliferation, and secretion as well VEGF-A and VEGFR-2 expression by immunohistochemistry. In vitro, we evaluated the effects of TC on cholangiocyte secretion of VEGF-A and the dependence of TC-induced proliferation on the activity of VEGFR-2. RESULTS: In BDL rats with HAL, chronic feeding of TC prevented HAL-induced loss of bile ducts and HAL-induced decreased cholangiocyte secretion. TC also prevented HAL inhibited VEGF-A and VEGFR-2 expression in liver sections and HAL-induced circulating VEGF-A levels, which were blocked by wortmannin administration. In vitro, TC stimulated increased VEGF-A secretion by cholangiocytes, which was blocked by wortmannin and stimulated cholangiocyte proliferation that was blocked by VEGFR-2 kinase inhibitor. CONCLUSION: TC prevented HAL-induced biliary damage by upregulation of VEGF-A expression. PMID- 20303840 TI - Sustained virological response following extremely short antiviral treatment in selected HCV carriers with persistently normal ALT. PMID- 20303841 TI - Cerebral consequences of dynamic immobilisation after primary digital flexor tendon repair. AB - Current treatment protocols for flexor tendon injuries of the hand generally result in an acceptable function, which can be quantified by objective parameters such as range of motion. The latter does not always match the patients' subjective experiences of persisting dysfunction. This raises the question whether changes in the cerebral control of movement might contribute to the perceived deficit. The main objective of the present positron emission tomography (PET) study was to characterise the cerebral responses in movement-associated areas during simple finger flexion immediately after dynamic immobilisation and after a subsequent 6-week period of active training. Ten subjects with flexor tendon injury participated in the PET study. Electromyography (EMG) recordings were made during finger flexion and extension in an additional subject. The main finding was that the (ventral) putamen contralateral to flexor movement was not activated immediately after release from splinting, while such activation reappeared after a period of training. This indicates a temporary loss of efficient motor control of over-learnt movements. The increase of unwanted co contractions during flexion in a first EMG session, and not during extension, supports a concept of lost skills. PMID- 20303842 TI - Delay of denervation atrophy by sensory protection in an end-to-side neurorrhaphy model: a pilot study. AB - OBJECT: Temporary sensory innervation delays the atrophy process. A major disadvantage of most experimental models is that sensory-protected muscles must be denervated a second time to allow reinnervation by the affected nerve. The aim of this study was to assess the effect of sensory protection on denervated gastrocnemius muscle in an end-to-side neurorrhaphy model, in which denervated muscles may be preserved until axons of the native nerve reach their target without the necessity for a second operation. METHODS: The tibial nerve of 24 female Lewis rats was transected. Twelve animals acted as the controls. In the other 12 animals, the end of the sural nerve was connected to the side of the distal tibial nerve stump (sensory protection group). At 5 and 10 weeks, wet gastrocnemius muscle weight was reported as a ratio of the operated to the unoperated side. For histological analysis, muscle samples were rapidly frozen and sections were stained with haematoxylin and eosin, Oil Red O stain and modified Gomori trichrome stain. RESULTS: The difference between the sensory protection group and the control group was statistically significant at 5 (0.36+/ 0.01 and 0.29+/-0.01, respectively; p<0.001) and 10 weeks postoperatively (0.28+/ 0.01 and 0.19+/-0.00, respectively; p<0.001). Histological observations revealed that sensory-protected muscles underwent less atrophy. CONCLUSION: Sensory protection delays atrophy in an end-to-side neurorrhaphy model. PMID- 20303843 TI - Efficacy of transesophageal and transgastric cardiac pacing in the dog. AB - OBJECTIVES: Determine if temporary artificial cardiac pacing can be accomplished from transesophageal or transgastric pacing sites. ANIMALS, MATERIALS AND METHODS: Nine purpose bred Beagle dogs had a multipolar electrophysiology pacing catheter inserted transnasally and advanced into the distal esophagus or stomach under general anesthesia. Artificial atrial pacing was attempted using a bipolar configuration from the distal esophagus with the dogs in left lateral recumbency. Artificial ventricular pacing was attempted from the distal esophagus and stomach using unipolar and bipolar configurations with the dogs in multiple positions. RESULTS: Transesophageal atrial pacing was accomplished in all dogs with a mean threshold of 10.5 mA (+ or - 3.9) and a 15 mm polar separation with no skeletal muscle stimulation. All attempts at transgastric and transesophageal ventricular pacing were unsuccessful. CONCLUSIONS: Transesophageal atrial pacing using standard cardiac pacing equipment is simple to perform and is a viable alternative to temporary transvenous or transthoracic pacing for supraventricular bradyarrhythmias without atrioventricular conduction disturbances. Transesophageal and transgastric ventricular pacing does not appear possible using the pacing configurations in this study. PMID- 20303844 TI - Prevalence and correlates of recent and repeat mammography among California women ages 55-79. AB - OBJECTIVE: Data on repeat mammography rates are less available than for recent screening. Two large, population-based state surveys provide the opportunity to investigate repeat and recent mammography prevalence and correlates among California's diverse population. METHODS: Data were from women aged 55-79, using the 2001 and 2005 California Health Interview Surveys. The study assessed the prevalence and correlates of recent mammography (within the past two years) and repeat mammography (mammogram within the past two years and 3-11 mammograms within the past six years). RESULTS: Prevalence was 82.4% (recent) and 73.8% (repeat) in 2001, and 87.1% (recent) and 77.5% (repeat) in 2005. Correlates of lower rates were insurance status, no usual source of care, being a smoker, age 65-79, being Asian with no English proficiency, being never married, and lower absolute risk for breast cancer. Especially low ratios of repeat-to-recent mammography existed for the uninsured, and those using the emergency room or with no source of care. Unexpected findings in which unadjusted results were inconsistent with multivariable adjusted results occurred for Latinas with no English proficiency and women at 200-299% of poverty level. CONCLUSIONS: Several groups of women in California remain at-risk of lower mammography utilization. However, investigators should also be alert for instances where multivariable analyses seem particularly discrepant with crude rates. PMID- 20303845 TI - Proteolytic scanning calorimetry: a novel methodology that probes the fundamental features of protein kinetic stability. AB - We introduce proteolytic scanning calorimetry, a modification of the differential scanning calorimetry approach to the determination of protein stability in which a proteolytic enzyme (thermolysin) is used to mimic a harsh environment. This methodology allows the straightforward calculation of the rate of irreversible denaturation as a function of temperature and concentration of proteolytic enzyme and, as a result, has the potential to probe efficiently the fundamental biophysical features of protein kinetic stability. In the particular case of Escherichia coli thioredoxin (used as an illustrative example in this article), we find that the rate of irreversible denaturation is determined by 1), the global unfolding mechanism at low thermolysin concentrations, indicating that thermodynamic stability may contribute directly to the kinetic stability of thioredoxin under moderately harsh conditions and 2), the rate of unfolding at high thermolysin concentrations, indicating that the free-energy barrier for unfolding may act as a safety mechanism that ensures significant kinetic stability, even in very harsh environments. This thioredoxin picture, however, is by no means expected to be general and different proteins may show different patterns of kinetic stabilization. Proteolytic scanning calorimetry is particularly well-suited to probe this diversity at a fundamental biophysical level. PMID- 20303846 TI - From induced fit to conformational selection: a continuum of binding mechanism controlled by the timescale of conformational transitions. AB - In receptor-ligand binding, a question that generated considerable interest is whether the mechanism is induced fit or conformational selection. This question is addressed here by a solvable model, in which a receptor undergoes transitions between active and inactive forms. The inactive form is favored while unbound but the active form is favored while a ligand is loosely bound. As the active inactive transition rates increase, the binding mechanism gradually shifts from conformational selection to induced fit. The timescale of conformational transitions thus plays a crucial role in controlling binding mechanisms. PMID- 20303847 TI - Increased sensitivity and extended range of distance measurements in spin-labeled membrane proteins: Q-band double electron-electron resonance and nanoscale bilayers. AB - We report a significant methodological advance in the application of double electron-electron resonance (DEER) spectroscopy to measure long-range distances in spin-labeled membrane proteins. In the pseudo two-dimensional environment of proteoliposomes, a steep intermolecular background shapes DEER signals leading to long accumulation times, complicating data analysis and reducing the maximal measurable distances from 70 A down to approximately 40-50 A. To eliminate these limitations, we took advantage of the homogeneity and monodispersity of a class of discoidal nanoscale phospholipid bilayers in conjunction with the micromolar DEER sensitivity at Q-band (34 GHz) microwave frequency. Spin-labeled mutants of the ABC transporter MsbA were functionally reconstituted at a ratio of one functional dimer per nanoscale apolipoprotein-bound bilayer (NABB). DEER echo intensities from NABB-reconstituted MsbA have linear baselines reflecting a three dimensional spatial distribution. This results in an order-of-magnitude higher sensitivity at Q-band relative to proteoliposomes and restores the maximal observable distance effectively increasing experimental throughput. The advances described here set the stage for the use of DEER spectroscopy to analyze conformational dynamics of sample-limited eukaryotic membrane proteins. PMID- 20303848 TI - Line active hybrid lipids determine domain size in phase separation of saturated and unsaturated lipids. AB - A simple model of the line activity of a hybrid lipid (e.g., POPC) with one fully saturated chain and one partially unsaturated chain demonstrates that these lipids preferentially pack at curved interfaces between phase-separated saturated and unsaturated domains. We predict that the domain sizes typically range from tens to hundreds of nm, depending on molecular interactions and parameters such as molecular volume and area per headgroup in the bulk fluid phase. The role of cholesterol is taken into account by an effective change in the headgroup areas and the domain sizes are predicted to increase with cholesterol concentration. PMID- 20303849 TI - Interpreting membrane scattering experiments at the mesoscale: the contribution of dissipation within the bilayer. AB - Neutron spin-echo spectroscopy provides a means to study membrane undulation dynamics over length scales roughly spanning 10-100 nanometers. Modern interpretation of these measurements relies on the theoretical predictions of Zilman and Granek; however, it is necessary to introduce an anomalously large solvent viscosity within this theory to obtain quantitative agreement with experiment. An extended theoretical treatment is presented that includes the effects of internal dissipation within the bilayer. Within the length and time regimes appropriate to neutron spin-echo experiments, the results of Zilman and Granek are largely recovered, except that the bilayer curvature modulus kappa appearing in their theory must be replaced with an effective dynamic curvature modulus kappa =kappa+2d(2)k(m), where d is a distance comparable to the monolayer thickness (the height of the neutral surface from bilayer midplane) and k(m) is the monolayer compressibility modulus. Direct comparison between theory and experiment becomes possible without any rescaling of physical parameters. PMID- 20303850 TI - Bipedal locomotion in crawling cells. AB - Many complex cellular processes from mitosis to cell motility depend on the ability of the cytoskeleton to generate force. Force-generating systems that act on elastic cytoskeletal elements are prone to oscillating instabilities. In this work, we have measured spontaneous shape and movement oscillations in motile fish epithelial keratocytes. In persistently polarized, fan-shaped cells, retraction of the trailing edge on one side of the cell body is out of phase with retraction on the other side, resulting in periodic lateral oscillation of the cell body. We present a physical description of keratocyte oscillation in which periodic retraction of the trailing edge is the result of elastic coupling with the leading edge. Consistent with the predictions of this model, the observed frequency of oscillation correlates with cell speed. In addition, decreasing the strength of adhesion to the substrate reduces the elastic force required for retraction, causing cells to oscillate with higher frequency at relatively lower speeds. These results demonstrate that simple elastic coupling between movement at the front of the cell and movement at the rear can generate large-scale mechanical integration of cell behavior. PMID- 20303851 TI - A Wnt oscillator model for somitogenesis. AB - We propose a model for the segmentation clock in vertebrate somitogenesis, based on the Wnt signaling pathway. The core of the model is a negative feedback loop centered around the Axin2 protein. Axin2 is activated by beta-catenin, which in turn is degraded by a complex of GSK3beta and Axin2. The model produces oscillatory states of the involved constituents with typical time periods of a few hours (ultradian oscillations). The oscillations are robust to changes in parameter values and are often spiky, where low concentration values of beta catenin are interrupted by sharp peaks. Necessary for the oscillations is the saturated degradation of Axin2. Somite formation in chick and mouse embryos is controlled by a spatial Wnt gradient which we introduce in the model through a time-dependent decrease in Wnt3a ligand level. We find that the oscillations disappear as the ligand concentration decreases, in agreement with observations on embryos. PMID- 20303852 TI - Crowding effects on association reactions at membranes. AB - The effect of macromolecular crowding on the binding of ligands to a receptor near membranes is studied using Brownian dynamics simulations. The receptor is modeled as a reactive patch on a hard surface and the ligands and crowding agents are modeled as spheres that interact via a steep repulsive interaction potential. When a ligand collides with the patch, it reacts with probability p(rxn). The association rate constant (k(infinity)) can be decomposed into contributions from diffusion-limited (k(D)) and reaction-limited (k(R)) rates, i.e., 1/k(infinity) = 1/k(D) + 1/k(R). The simulations show that k(D) is a nonmonotonic function of the volume fraction of crowding agents for receptors of small sizes. k(R) is always an increasing function of the volume fraction of crowding agents, and the association rate constant k(infinity) determined from both contributions has a qualitatively different dependence on the macromolecular crowding for high and low values of the reaction probability p(rxn). The simulation results are used to predict the velocity of the membrane protrusion driven by actin filament elongation. Based on the simple model where the protrusive force on the membrane is generated by the intercalation of actin monomers between the membrane and actin filament ends, we predict that crowding increases the local concentration of actin monomers near the filament ends and hence accelerates the membrane protrusion. PMID- 20303853 TI - Monte Carlo simulation of buffered diffusion into and out of a model synapse. AB - Buffered diffusion occurs when ligands enter or leave a restricted space, such as a chemical synapse, containing a high density of binding sites. This study used Monte Carlo simulations to determine the time and spatial dependences of buffered diffusion without a priori assumptions about kinetics. The synapse was modeled as a box with receptors on one inner face. The exterior was clamped to some ligand concentration and ligands diffused through two sides. Onset and recovery simulations were carried out and the effects of receptor density, ligand properties and synapse geometry were investigated. This study determined equilibration times for binding and the spatial gradient of unliganded receptors. Onset was characterized by a high spatial gradient; equilibration was limited by the time needed for sufficient ligands to enter the synapse. Recovery showed a low spatial gradient with receptor equilibration limited by ligand rebinding. Decreasing ligand association rate or increasing ligand diffusion coefficient reduced the role of buffered diffusion and decreased the spatial gradient. Simulations with irreversible ligands showed larger, persistent spatial gradients. These simulations identify characteristics that can be used to test whether a synaptic process is governed by buffered diffusion. They also indicate that fundamental differences in synapse function may occur with irreversible ligands. PMID- 20303854 TI - Synaptotagmin IV modulation of vesicle size and fusion pores in PC12 cells. AB - Many synaptotagmins are Ca(2+)-binding membrane proteins with functions in Ca(2+) triggered exocytosis. Synaptotagmin IV (syt IV) has no Ca(2+) binding activity, but nevertheless modulates exocytosis. Here, cell-attached capacitance recording was used to study single vesicle fusion and fission in control and syt IV overexpressing PC12 cells. Unitary capacitance steps varied widely in size, indicating that both microvesicles (MVs) and dense-core vesicles (DCVs) undergo fusion. Syt IV overexpression reduced the size of DCVs and endocytotic vesicles but not MVs. Syt IV also reduced the basal rate of Ca(2+)-induced fusion. During kiss-and-run, syt IV increased the conductance and duration of DCV fusion pores but not MV fusion pores. During full-fusion of DCVs syt IV increased the fusion pore conductance but not the duration. Syt IV overexpression increased the duration but not the conductance of fission pores during endocytosis. The effects of syt IV on fusion pores in PC12 cells resembled the effects on fusion pores in peptidergic nerve terminals. However, differences between these and results obtained with amperometry may indicate that amperometry and capacitance detect the fusion of different populations of vesicles. The effects of syt IV on fusion pores are discussed in terms of structural models and kinetic mechanisms. PMID- 20303856 TI - Cations mediate interactions between the nicotinic acetylcholine receptor and anionic lipids. AB - Interactions between the nicotinic acetylcholine receptor (nAChR) and phosphatidic acid (PA) are bidirectional in that membranes containing PA are effective at stabilizing an agonist-responsive nAChR, whereas incorporation of the nAChR into the same membranes leads to a substantial increase in lipid lateral packing density. A previous study suggested that the ability of PA to adopt a dianionic ionization state is key. We monitored the ionization state of PA in both reconstituted and protein-free membranes. In model membranes composed of PA and 3:2 (mol/mol) phosphatidylcholine (PC)/PA, the monoanionic-to-dianionic transition of PA was detected with a pKa of 8.7 and 6.5, respectively. In the reconstituted 3:2 PC/PA membranes, however, PA was stabilized in a monoanionic state at pH values up to 10. Although dianionic PA does not play a role in nAChR function, we found that both the stabilization of monoanionic PA and the concentration of other cations at the bilayer surface can account for changes in bilayer physical properties that are observed upon incorporation of the nAChR into 3:2 PC/PA membranes. A nAChR-induced concentration of cations at the bilayer surface likely mediates interactions between the nAChR and the anionic lipids in its membrane environment. PMID- 20303855 TI - Force generation in lamellipodia is a probabilistic process with fast growth and retraction events. AB - Polymerization of actin filaments is the primary source of motility in lamellipodia and it is controlled by a variety of regulatory proteins. The underlying molecular mechanisms are only partially understood and a precise determination of dynamical properties of force generation is necessary. Using optical tweezers, we have measured with millisecond (ms) temporal resolution and picoNewton (pN) sensitivity the force-velocity (Fv) relationship and the power dissipated by lamellipodia of dorsal root ganglia neurons. When force and velocity are averaged over 3-5 s, the Fv relationships can be flat. On a finer timescale, random occurrence of fast growth and subsecond retractions become predominant. The maximal power dissipated by lamellipodia over a silica bead with a diameter of 1 microm is 10(-16) W. Our results clarify the dynamical properties of force generation: i), force generation is a probabilistic process; ii), underlying biological events have a bandwidth up to at least 10 Hz; and iii), fast growth of lamellipodia leading edge alternates with local retractions. PMID- 20303857 TI - Antiport mechanism for Cl(-)/H(+) in ClC-ec1 from normal-mode analysis. AB - ClC chloride channels and transporters play major roles in cellular excitability, epithelial salt transport, volume, pH, and blood pressure regulation. One family member, ClC-ec1 from Escherichia coli, has been structurally resolved crystallographically and subjected to intensive mutagenetic, crystallographic, and electrophysiological studies. It functions as a Cl(-)/H(+) antiporter, not a Cl(-) channel; however, the molecular mechanism for Cl(-)/H(+) exchange is largely unknown. Using all-atom normal-mode analysis to explore possible mechanisms for this antiport, we propose that Cl(-)/H(+) exchange involves a conformational cycle of alternating exposure of Cl(-) and H(+) binding sites of both ClC pores to the two sides of the membrane. Both pores switch simultaneously from facing outward to facing inward, reminiscent of the standard alternating access mechanism, which may have direct implications for eukaryotic Cl(-)/H(+) transporters and Cl(-) channels. PMID- 20303858 TI - Molecular dynamics simulations of the rotary motor F(0) under external electric fields across the membrane. AB - The membrane-bound component F(0), which is a major component of the F(0)F(1)-ATP synthase, works as a rotary motor and plays a central role in driving the F(1) component to transform chemiosmotic energy into ATP synthesis. We conducted molecular dynamics simulations of b(2)-free F(0) in a 1-palmitoyl-2-oleoyl phosphatidylcholine lipid bilayer for tens of nanoseconds with two different protonation states of the cAsp-61 residue at the interface of the a-c complex in the absence of electric fields and under electric fields of +/-0.03 V/nm across the membrane. To our surprise, we observed that the upper half of the N-terminal helix of the c(1) subunit rotated about its axis clockwise by 30 degrees . An energetic analysis revealed that the electrostatic repulsion between this N terminal helix and subunit c(12) was a major contributor to the observed rotation. A correlation map analysis indicated that the correlated motions of residues in the interface of the a-c complex were significantly reduced by external electric fields. The deuterium order parameter (S(CD)) profile calculated by averaging all the lipids in the F(0)-bound bilayer was not very different from that of the pure bilayer system, in agreement with recent (2)H solid-state NMR experiments. However, by delineating the lipid properties according to their vicinity to F(0), we found that the S(CD) profiles of different lipid shells were prominently different. Lipids close to F(0) formed a more ordered structure. Similarly, the lateral diffusion of lipids on the membrane surface also followed a shell-dependent behavior. The lipids in the proximity of F(0) exhibited very significantly reduced diffusional motion. The numerical value of S(CD) was anticorrelated with that of the diffusion coefficient, i.e., the more ordered lipid structures led to slower lipid diffusion. Our findings will help elucidate the dynamics of F(0) depending on the protonation state and electric field, and may also shed some light on the interactions between the motor F(0) and its surrounding lipids under physiological conditions, which could help to rationalize its extraordinary energy conversion efficiency. PMID- 20303859 TI - Gadolinium ions block mechanosensitive channels by altering the packing and lateral pressure of anionic lipids. AB - Effects of polyvalent ions on the lateral packing of phospholipids have been known for decades, but the physiological consequences have not been systematically studied. Gd(3+) is a relatively nonspecific agent that blocks mechano-gated channels with a variable affinity. In this study, we show that the large mechanosensitive channel MscL of Escherichia coli is effectively blocked by Gd(3+) only when reconstituted with negatively charged phospholipids (e.g., PS). Taking this lead, we studied effects of Gd(3+) on monolayers and unilamellar vesicles made of natural brain PS, DMPS, and its mixtures with DMPC. In monolayer experiments, we found that muM Gd(3+) present in the subphase leads to approximately 8% lateral compaction of brain PS (at 35 mN/m). Gd(3+) more strongly shrinks and rigidifies DMPS films causing a spontaneous liquid expanded to-compact transition to the limiting 40 A(2)/mol. Pressure-area isotherms of uncharged DMPC were unaffected by Gd(3+), and neutralization of DMPS surface by low pH did not produce strong compaction. Upshifts of surface potential isotherms of DMPS monolayers reflected changes in the diffuse double layer due to neutralization of headgroup charges by Gd(3+), whereas the increased packing density produced up to a 200 mV change in the interfacial dipole potential. The slopes of surface potential versus reciprocal area predicted that Gd(3+) induced a modest ( approximately 18%) increase in the magnitude of the individual lipid dipoles in DMPS. Isothermal titration calorimetry indicated that binding of Gd(3+) to DMPS liposomes in the gel state is endothermic, whereas binding to liquid crystalline liposomes produces heat consistent with the isothermal liquid to-gel phase transition induced by the ion. Both titration curves suggested a K(b) of approximately 10(6) M(-1). We conclude that anionic phospholipids serve as high-affinity receptors for Gd(3+) ions, and the ion-induced compaction generates a lateral pressure increase estimated as tens of mN/m. This pressure can "squeeze" the channel and shift the equilibrium toward the closed state. PMID- 20303860 TI - Exploring the conformational space of chromatin fibers and their stability by numerical dynamic phase diagrams. AB - The three-dimensional structure of chromatin affects DNA accessibility and is therefore a key regulator of gene expression. However, the path of the DNA between consecutive nucleosomes, and the resulting chromatin fiber organization remain controversial. The conformational space available for the folding of the nucleosome chain has been analytically described by phase diagrams with a two angle model, which describes the chain trajectory by a DNA entry-exit angle at the nucleosome and a torsion angle between consecutive nucleosomes. Here, a novel type of numerical phase diagrams is introduced that relates the geometric phase space to the energy associated with a given chromatin conformation. The resulting phase diagrams revealed differences in the energy landscape that reflect the probability of a given conformation to form in thermal equilibrium. Furthermore, we investigated the effects of entropy and additional degrees of freedom in the dynamic phase diagrams by performing Monte Carlo simulations of the initial chain trajectories. Using our approach, we were able to demonstrate that conformations that initially were geometrically impossible could evolve into energetically favorable states in thermal equilibrium due to DNA bending and torsion. In addition, dynamic phase diagrams were applied to identify chromatin fibers that reflect certain experimentally determined features. PMID- 20303861 TI - GNNQQNY--investigation of early steps during amyloid formation. AB - Protein aggregation has been implicated in the pathology of several neurodegenerative diseases, and a better understanding of how it proceeds is essential for the development of therapeutic strategies. Recently, the amyloidogenic heptapeptide GNNQQNY has emerged as a molecule of choice for fundamental studies of protein aggregation. A number of experimental and computational studies have examined the structure of the GNNQQNY aggregate. Less work, however, has been aimed at understanding its aggregation pathway. In this study, we present a detailed computational analysis of such a pathway. To that end, transition path sampling Monte Carlo simulations are used to examine the dimerization process. A statistical analysis of the reaction pathways shows that the dimerization reaction proceeds via a zipping mechanism, initiated with the formation of distinct contacts at the third residue (N). Asparagine residues are found to play a key role in the early stages of aggregation. And, contrary to previous belief, it is also shown that the tyrosine terminal group is not required to stabilize the dimer. In fact, an asparagine residue leads to faster aggregation of the peptide. PMID- 20303862 TI - Union of geometric constraint-based simulations with molecular dynamics for protein structure prediction. AB - Although proteins are a fundamental unit in biology, the mechanism by which proteins fold into their native state is not well understood. In this work, we explore the assembly of secondary structure units via geometric constraint-based simulations and the effect of refinement of assembled structures using reservoir replica exchange molecular dynamics. Our approach uses two crucial features of these methods: i), geometric simulations speed up the search for nativelike topologies as there are no energy barriers to overcome; and ii), molecular dynamics identifies the low free energy structures and further refines these structures toward the actual native conformation. We use eight alpha-, beta-, and alpha/beta-proteins to test our method. The geometric simulations of our test set result in an average RMSD from native of 3.7 A and this further reduces to 2.7 A after refinement. We also explore the question of robustness of assembly for inaccurate (shifted and shortened) secondary structure. We find that the RMSD from native is highly dependent on the accuracy of secondary structure input, and even slightly shifting the location of secondary structure along the amino acid sequence can lead to a rapid decrease in RMSD to native due to incorrect packing. PMID- 20303863 TI - Conformational analysis of the partially disordered measles virus N(TAIL)-XD complex by SDSL EPR spectroscopy. AB - To characterize the structure of dynamic protein systems, such as partly disordered protein complexes, we propose a novel approach that relies on a combination of site-directed spin-labeled electron paramagnetic resonance spectroscopy and modeling of local rotation conformational spaces. We applied this approach to the intrinsically disordered C-terminal domain of the measles virus nucleoprotein (N(TAIL)) both free and in complex with the X domain (XD, aa 459-507) of the viral phosphoprotein. By comparing measured and modeled temperature-dependent restrictions of the side-chain conformational spaces of 12 SL cysteine-substituted N(TAIL) variants, we showed that the 490-500 region of N(TAIL) is prestructured in the absence of the partner, and were able to quantitatively estimate, for the first time to our knowledge, the extent of the alpha-helical sampling of the free form. In addition, we showed that the 505-525 region of N(TAIL) conserves a significant degree of freedom even in the bound form. The latter two findings provide a mechanistic explanation for the reported rather high affinity of the N(TAIL)-XD binding reaction. Due to the nanosecond timescale of X-band EPR spectroscopy, we were also able to monitor the disordering in the 488-525 region of N(TAIL), in particular the unfolding of the alpha-helical region when the temperature was increased from 281 K to 310 K. PMID- 20303864 TI - Understanding the concentration dependence of viral capsid assembly kinetics--the origin of the lag time and identifying the critical nucleus size. AB - The kinetics for the assembly of viral proteins into a population of capsids can be measured in vitro with size exclusion chromatography or dynamic light scattering, but extracting mechanistic information from these studies is challenging. For example, it is not straightforward to determine the critical nucleus size or the elongation time (the time required for a nucleus to grow to completion). In this work, we study theoretical and computational models for capsid assembly to show that the critical nucleus size can be determined from the concentration dependence of the assembly half-life and that the elongation time is revealed by the length of the lag phase. Furthermore, we find that the system becomes kinetically trapped when nucleation becomes fast compared to elongation. Implications of this constraint for determining elongation mechanisms from experimental assembly data are discussed. PMID- 20303865 TI - Hydration potential of lysozyme: protein dehydration using a single microparticle technique. AB - For biological molecules in aqueous solution, the hydration pressure as a function of distance from the molecular surface represents a very short-range repulsive pressure that limits atom-atom contact, opposing the attractive van der Waals pressure. Whereas the separation distance for molecules that easily arrange into ordered arrays (e.g., lipids, DNA, collagen fibers) can be determined from x ray diffraction, many globular proteins are not as easily structured. Using a new micropipette technique, spherical, glassified protein microbeads can be made that allow determination of protein hydration as a function of the water activity (a(w)) in a surrounding medium (decanol). By adjusting a(w) of the dehydration medium, the final protein concentration of the solid microbead is controlled, and ranges from 700 to 1150 mg/mL. By controlling a(w) (and thus the osmotic pressure) around lysozyme, the repulsive pressure was determined as a function of distance between each globular, ellipsoid protein. For separation distances, d, between 2.5 and 9 A, the repulsive decay length was 1.7 A and the pressure extrapolated to d = 0 was 2.2 x 10(8) N/m(2), indicating that the hydration pressure for lysozyme is similar to other biological interfaces such as phospholipid bilayers. PMID- 20303867 TI - Inflammation 2010: new adventures of an old flame. AB - Inflammation is an essential immune response that enables survival during infection or injury and maintains tissue homeostasis under a variety of noxious conditions. Inflammation comes at the cost of a transient decline in tissue function, which can in turn contribute to the pathogenesis of diseases of altered homeostasis. PMID- 20303866 TI - Tertiary and secondary structure elasticity of a six-Ig titin chain. AB - The protein titin functions as a mechanical spring conferring passive elasticity to muscle. Force spectroscopy studies have shown that titin exhibits several regimes of elasticity. Disordered segments bring about a soft, entropic spring type elasticity; secondary structures of titin's immunoglobulin-like (Ig-) and fibronectin type III-like (FN-III) domains provide a stiff elasticity. In this study, we demonstrate a third type of elasticity due to tertiary structure and involving domain-domain interaction and reorganization along the titin chain. Through 870 ns of molecular dynamics simulations involving 29,000-635,000 atom systems, the mechanical properties of a six-Ig domain segment of titin (I65-I70), for which a crystallographic structure is available, are probed. The results reveal a soft tertiary structure elasticity. A remarkably accurate statistical mechanical description for this elasticity is derived and applied. Simulations also studied the stiff, secondary structure elasticity of the I65-I70 chain due to the unraveling of its domains and revealed how force propagates along the chain during the secondary structure elasticity response. PMID- 20303868 TI - Asthma and allergic inflammation. AB - Studies of the initiation and maintenance of asthma and allergic inflammation implicate dysregulated interactions between mucosal epithelia and innate immune cells as the underlying cause of these disorders. The similarities of these responses with mucosal responses to parasitic intestinal worms may reveal pathways relevant to the perplexing rise of these chronic inflammatory disorders. PMID- 20303869 TI - Autoinflammatory disease reloaded: a clinical perspective. AB - Our understanding of the etiology of autoinflammatory disease is growing rapidly. Recent advances offer new opportunities for therapeutic intervention and suggest that the definition of what constitutes an autoinflammatory disease should be reassessed. PMID- 20303870 TI - Unraveling the genetics of autoimmunity. AB - The chronic autoimmune diseases include multiple complex genetic disorders. Recently, genome-wide association studies (GWAS) have identified a large number of major loci, with many associations shared between various autoimmune diseases. These associations highlight key roles for lymphocyte activation and prioritize specific cytokine pathways and mechanisms of host-microbe recognition. Despite success in identifying loci, comprehensive models of disease pathogenesis are currently lacking. Future efforts comparing association patterns between autoimmune diseases may be particularly illustrative. New genomic technologies applied to classic genetic studies involving twins, early onset cases, and phenotypic extremes may provide key insights into developmental and gene environment interactions in autoimmunity. PMID- 20303871 TI - Decoding cell death signals in inflammation and immunity. AB - Dying cells release and expose at their surface molecules that signal to the immune system. We speculate that combinations of these molecules determine the route by which dying cells are engulfed and the nature of the immune response that their death elicits. PMID- 20303872 TI - Pattern recognition receptors and inflammation. AB - Infection of cells by microorganisms activates the inflammatory response. The initial sensing of infection is mediated by innate pattern recognition receptors (PRRs), which include Toll-like receptors, RIG-I-like receptors, NOD-like receptors, and C-type lectin receptors. The intracellular signaling cascades triggered by these PRRs lead to transcriptional expression of inflammatory mediators that coordinate the elimination of pathogens and infected cells. However, aberrant activation of this system leads to immunodeficiency, septic shock, or induction of autoimmunity. In this Review, we discuss the role of PRRs, their signaling pathways, and how they control inflammatory responses. PMID- 20303873 TI - The inflammasomes. AB - Inflammasomes are molecular platforms activated upon cellular infection or stress that trigger the maturation of proinflammatory cytokines such as interleukin 1beta to engage innate immune defenses. Strong associations between dysregulated inflammasome activity and human heritable and acquired inflammatory diseases highlight the importance this pathway in tailoring immune responses. Here, we comprehensively review mechanisms directing normal inflammasome function and its dysregulation in disease. Agonists and activation mechanisms of the NLRP1, NLRP3, IPAF, and AIM2 inflammasomes are discussed. Regulatory mechanisms that potentiate or limit inflammasome activation are examined, as well as emerging links between the inflammasome and pyroptosis and autophagy. PMID- 20303874 TI - Selective transcription in response to an inflammatory stimulus. AB - An inflammatory response is initiated by the temporally controlled activation of genes encoding a broad range of regulatory and effector proteins. A central goal is to devise strategies for the selective modulation of proinflammatory gene transcription, to allow the suppression of genes responsible for inflammation associated pathologies while maintaining a robust host response to microbial infection. Toward this goal, recent studies have revealed an unexpected level of diversity in the mechanisms by which chromatin structure and individual transcription factors contribute to the selective regulation of inflammatory genes. PMID- 20303875 TI - Th17 and regulatory T cells in mediating and restraining inflammation. AB - The vertebrate immune system is poised in a state of equilibrium that permits accurate and rapid protective responses against pathogens but curtails potential for causing harm to the host through targeting of "self" and provoking overexuberant inflammatory processes. In this Review we discuss this balance achieved in large part by interactions of different classes of T lymphocytes that have potent pro- or anti-inflammatory activity in the context of genetic and environmental factors, particularly the commensal microbiota. PMID- 20303876 TI - Homeostasis and inflammation in the intestine. AB - The gut is home to our largest collection of microbes. The ability of the immune system to coevolve with the microbiota during postnatal life allows the host and microbiota to coexist in a mutually beneficial relationship. Failure to achieve or maintain equilibrium between a host and its microbiota has negative consequences for both intestinal and systemic health. In this Review, we consider the many cellular and molecular methods by which inflammatory responses are regulated to maintain intestinal homeostasis and the disease states that can ensue when this balance is lost. PMID- 20303877 TI - Nonresolving inflammation. AB - Nonresolving inflammation is a major driver of disease. Perpetuation of inflammation is an inherent risk because inflammation can damage tissue and necrosis can provoke inflammation. Nonetheless, multiple mechanisms normally ensure resolution. Cells like macrophages switch phenotypes, secreted molecules like reactive oxygen intermediates switch impact from pro- to anti-inflammatory, and additional mediators of resolution arise, including proteins, lipids, and gasses. Aside from persistence of initiating stimuli, nonresolution may result from deficiencies in these mechanisms when an inflammatory response begins either excessively or subnormally. This greatly complicates the development of anti inflammatory therapies. The problem calls for conceptual, organizational, and statistical innovations. PMID- 20303878 TI - Immunity, inflammation, and cancer. AB - Inflammatory responses play decisive roles at different stages of tumor development, including initiation, promotion, malignant conversion, invasion, and metastasis. Inflammation also affects immune surveillance and responses to therapy. Immune cells that infiltrate tumors engage in an extensive and dynamic crosstalk with cancer cells, and some of the molecular events that mediate this dialog have been revealed. This review outlines the principal mechanisms that govern the effects of inflammation and immunity on tumor development and discusses attractive new targets for cancer therapy and prevention. PMID- 20303879 TI - Endoplasmic reticulum stress and the inflammatory basis of metabolic disease. AB - The endoplasmic reticulum (ER) is the major site in the cell for protein folding and trafficking and is central to many cellular functions. Failure of the ER's adaptive capacity results in activation of the unfolded protein response (UPR), which intersects with many different inflammatory and stress signaling pathways. These pathways are also critical in chronic metabolic diseases such as obesity, insulin resistance, and type 2 diabetes. The ER and related signaling networks are emerging as a potential site for the intersection of inflammation and metabolic disease. PMID- 20303880 TI - Mechanisms underlying inflammation in neurodegeneration. AB - Inflammation is associated with many neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and multiple sclerosis. In this Review, we discuss inducers, sensors, transducers, and effectors of neuroinflammation that contribute to neuronal dysfunction and death. Although inducers of inflammation may be generated in a disease-specific manner, there is evidence for a remarkable convergence in the mechanisms responsible for the sensing, transduction, and amplification of inflammatory processes that result in the production of neurotoxic mediators. A major unanswered question is whether pharmacological inhibition of inflammation pathways will be able to safely reverse or slow the course of disease. PMID- 20303882 TI - SnapShot: Reactive Oxygen Intermediates (ROI). PMID- 20303881 TI - Anti-inflammatory Agents: Present and Future. AB - Inflammation involving the innate and adaptive immune systems is a normal response to infection. However, when allowed to continue unchecked, inflammation may result in autoimmune or autoinflammatory disorders, neurodegenerative disease, or cancer. A variety of safe and effective anti-inflammatory agents are available, including aspirin and other nonsteroidal anti-inflammatories, with many more drugs under development. In particular, the new era of anti inflammatory agents includes "biologicals" such as anticytokine therapies and small molecules that block the activity of kinases. Other anti-inflammatories currently in use or under development include statins, histone deacetylase inhibitors, PPAR agonists, and small RNAs. This Review discusses the current status of anti-inflammatory drug research and the development of new anti inflammatory therapeutics. PMID- 20303883 TI - Shortages of general and specialist surgeons. PMID- 20303884 TI - Spontaneous pneumomediastinum (Hamman's syndrome). AB - INTRODUCTION: Spontaneous pneumomediastinum is defined as the presence of free air in the mediastium in the absence of any obvious precipitating cause. The purpose of this study was to review our experience with this condition, discuss mechanisms and provide a management algorithm. METHODS: A retrospective audit of patients admitted with spontaneous pneumomediastinum between 2003 and 2008 was performed. A total of 17 patients were identified. RESULTS: Common predisposing factors for spontaneous pneumomediastinum were alcohol excess, asthma and illicit drug use. Vomiting and coughing were common precipitating factors. There was no morbidity, mortality or recurrence. Patients were admitted under a number of different specialties. DISCUSSION: Spontaneous pneumomediastinum is a benign self limiting condition that requires early differentiation from more serious causes, in particular Boerhaave's syndrome. PMID- 20303885 TI - Bilo-enteric fistula (BEF) at laparoscopic cholecystectomy: review of ten year's experience. AB - INTRODUCTION: BEF is a rare complication of gallstone disease with reported incidence of up to 4.8%. Most are diagnosed intra-operatively and often requires conversion to open surgery. This review assesses the feasibility of laparoscopic management of BEF found at the time of laparoscopic cholecystectomy over ten-year period. METHOD: All patients undergoing elective laparoscopic cholecystectomy by a single surgeon (PK) between 1996 and 2006 were prospectively entered in a database and analysed. RESULTS: Out of 824 laparoscopic cholecystectomy, ten cases of BEF were identified at operation (1.2%, age 14-88 years, median=62). These were cholecysto-duodenal (7), cholecysto-colonic (1), cholecysto-choledocho duodenal (1) and choledocho-duodenal (1). Two out of ten were converted to open surgery (20%) compared to overall conversion rate of 2.8% (23/824). Eight cases were successfully completed laparoscopically; endostapler was used in six patients to transect the fistula and two patients had the defect repaired by intra-corporeal sutures. No major complications were seen. One patient had a prolonged hospital stay for social reason. CONCLUSION: BEF is often detected intra-operatively and most can be managed laparoscopically successfully. Endostapling avoids peritoneal contamination and reduces operative time. PMID- 20303886 TI - Effect of deferred treatment of supracondylar humeral fractures. AB - PURPOSE: Timing of surgery remains a controversial topic in the treatment of the supracondylar humeral fracture. In our institution, patients are not brought to theatre after midnight, except in the 'life or limb' situation. We hypothesised that time to surgery has no significant influence on complication rate with supracondylar fracture of the humerus. METHODS: A retrospective review was performed of all patients who required operative intervention for supracondylar fractures of humerus between 2004 and 2006. Patients' charts were assessed for demographic details, fracture type, time to theatre and complications. Statistical comparisons were performed between different fracture grades. RESULTS: We identified 124 supracondylar fractures of humerus that required operative intervention between 2004 and 2006. Fractures were mainly treated with operative manipulation with medial and lateral crossed K-wire fixation. Gartland III and flexion type fractures had a significantly shorter time to surgery than Gartland II (p<0.05). There was no significant difference in complication rate between fractures operated after midnight or deferred until the morning (p=0.68). Most common complications identified were ulnar nerve palsy and AIN palsy. CONCLUSIONS: We have found no difference in complication rates when treatment of supracondylar fractures is delayed. Supracondylar fractures which are not grossly displaced, have no neurovascular deficit or risk of skin compromise, can be safely deferred without an increased risk of complication. Operative treatment of supracondylar fractures can be delayed until the next morning, except in the 'life or limb' situation. PMID- 20303887 TI - Failed laparoscopic anti-reflux surgery and indications for revision. A retrospective study. AB - Revisional anti-reflux surgery is required in certain patients for either early post-operative complications or recurrence of their original symptoms. The aim of this study is to review our revisional surgeries, learn the lessons and to highlight the treatment options for recurrent gastrooesophageal symptoms. MATERIALS AND METHODS: Three hundred and fifty one patients underwent laparoscopic anti-reflux surgery through January 2000 to March 2006 at our minimal access unit. Thirty-seven patients were diagnosed with failure of anti reflux surgery. Patient's data and follow up were retrieved from medical records. All recurrences were investigated for underlying cause and their managements were planned accordingly. RESULTS: Thirty-seven (10.54%) patients who developed early post-operative complications or recurrence of gastroesophageal symptoms were 25 women and 12 men. Heartburn was the commonest recurrent symptom. The majority of failures occurred in the first two years. Fourteen patients underwent revisional surgery while 23 patients were treated with acid reducing medications and showed a good response. The re-operation rate is 3.98%. There was no mortality and the total morbidity rate for revisional surgery is 7.14%. CONCLUSION: Early surgical complications of the initial procedures are managed by revisional surgery and the results were satisfactory provided these complications are detected early. Chronic failure of anti-reflux surgery can be managed by revisional surgery or medications depending on clinical symptoms and patients preference. PMID- 20303888 TI - Known knowns, known unknowns and unknown unknowns: a 2010 update on carotid artery disease. AB - The management of carotid artery disease never ceases to attract controversy. The last 12 months has seen publication of a number of important studies which have informed debate and 2010 holds the prospect of much more. This update offers a personal review of a number of contemporary issues including; (i) guidelines for non-invasive imaging in rapid access clinics, (ii) whether improvements in best medical therapy have rendered many of the conclusions from ACAS and ACST obsolete, (iii) is carotid disease really just a marker for increased stroke risk following cardiac surgery (rather than being an important cause), (iv) what is the current status of endarterectomy and stenting in patients with symptomatic carotid disease and (v) why we must offer expedited interventions to TIA/minor stroke patients. The available evidence suggests that while most 'known knowns' will endure, quite a few may be returning to the category of 'known unknowns' once again. Who knows what 'unknown unknowns' await us in 2010 and beyond. PMID- 20303889 TI - Surgical fires, a clear and present danger. AB - BACKGROUND: A surgical fire is potentially devastating for a patient. Fire has been recognised as a potential complication of surgery for many years. Surgical fires continue to happen with alarming frequency. We present a review of the literature and an examination of possible solutions to this problem. METHODS: The PubMed and Medline databases from 1948 onwards were searched using the subject headings "operating rooms", "fire", "safety" and "safety management". "Surgical fire" was also searched as a keyword. Relevant references from articles were obtained. RESULTS: Fire occurs when the three elements of the fire triad, fuel, oxidiser and ignition coincide. Surgical fires are unusual in the absence of an oxygen-enriched atmosphere. The ignition source is most commonly diathermy but lasers carry a relatively greater risk. The majority of fires occur during head and neck surgery. This is due to the presence of oxygen and the extensive use of lasers. The risk of fire can be reduced with an awareness of the risk and good communication. CONCLUSIONS: Surgery will always carry a risk of fire. Reducing this risk requires a concerted effort from all team members. PMID- 20303890 TI - Safe surgery, the human factors approach. AB - Studies estimate that a degree of error occurs in 5-15% of all hospital admissions, with 45% of errors occurring in the operating theatre. Staffing limitations, high turnover rates, site and side-specific surgical procedures, make operating theatres a high-risk environment. Valuable lessons may be learned from the aviation experience with error management. With over 70% of air-crashes occurring due to human rather than technical error, the Human Factors Approach to error recognises the potential for errors occurring due to human limitations, such as stress and fatigue. It encourages error reporting in a non-punitive environment, where it is seen as a valuable source of information, facilitating education and future error prevention. Errors in healthcare and surgery however, have been traditionally associated with secrecy and embarrassment, often reaching an unsatisfactory endpoint with no resultant education. Application of the Human Factors Approach to error management in healthcare, can only serve to improve safety standards in our hospitals and satisfy ever-increasing public expectations. PMID- 20303891 TI - Preventing healthcare-associated infection through education: have surgeons been overlooked? AB - BACKGROUND/AIMS: Some 20-30% of HCAI are considered to be preventable through an extensive infection prevention and control programme. Through an extensive literature review we aim to critically appraise studies which have utilised education initiatives to decrease HCAI. METHODS: An extensive review of the literature was carried out in both online medical journals and through the Royal College of Surgeons in Ireland library. FINDINGS: Many studies over the last 10 years have demonstrated success in educating nursing staff, critical care healthcare workers as well as medical students and junior doctors in the infection prevention and control of infection. Comparatively few have focussed on surgical trainees. A blended learning approach, with particular focus on the small group format is important. Interventions involving web-based learning in combination with established education formats are proving successful in changing behaviour. CONCLUSIONS: The development of an educational strategy for surgical trainees focussing on infection prevention and control is overdue. Such a programme would have far reaching benefits for individual patients, contribute to significant economic savings within health services and enhance the quality and safety of patient care. PMID- 20303892 TI - Emergency pre-hospital care of burn patients. AB - Intensive care and the surgical therapy of burn injuries have made significant advancements. The immediate care on the scene of the accident, however, is not uniform. There is no 'golden hour' which will decide the further clinical process. The acute estimate of the percentage of the extent of the burns is of little relevance and does not facilitate the admission to a burn unit. The emergency calculation of the volume of intravenous infusion is not advisable. The choice of transport has no discernible impact on the prognosis of the patient. Avoiding hypothermia and perceiving associated trauma can be of crucial prognostic importance in the pre-hospital care of burn patients. Detailed knowledge about the circumstances of the injury is of exceeding importance. PMID- 20303893 TI - Nutritional strategies in severe acute pancreatitis: a systematic review of the evidence. AB - Nutrition in severe acute pancreatitis is a critical aspect in the management of this condition. This review aims to systematically review the evidence available to inform the use of nutritional support in severe acute pancreatitis. High quality (level 1) evidence supports naso-jejunal enteral nutrition (NJ-EN) over parenteral nutrition (PN) reducing infectious morbidity and showing a trend towards reduced organ failure although there is no detectable difference in mortality. Trial data may underestimate benefit as patients are often recruited with predicted rather than proven severe disease. NJ-EN is safe when started immediately (level 3 evidence). NJ-EN is often impractical and naso-gastric (NG) feeding seems to be equivalent in terms of safety and outcomes whilst being more practical (level 2 evidence). Regarding feed supplementation, probiotic feed supplementation is not beneficial (level 1 evidence) the and may cause harm with excess mortality (level 2 evidence). No evidence exists to confirm benefit of the addition of prokinetics in severe acute pancreatitis (SAP) although their use is proven in other critically ill patients. Level 2 evidence does not currently support the use of combination immuno-nutrition though further work on individual agents may provide differing results. Level 2 evidence does not support intravenous supplementation of anti-oxidants and has demonstrated that these too may cause harm. PMID- 20303894 TI - The effects of smoking on fracture healing. AB - Tobacco smoking is the single most avoidable cause of premature death worldwide. In fracture healing, it has been found to be a contributory factor to delayed union, and smokers are significantly disadvantaged, as healing times are often prolonged. The orthopaedic surgeon is likely to be knowledgeable about the detrimental effects of smoking on healing bones, as the problem has been known for some time. Smoking adversely affects bone mineral density, lumbar disc degeneration, the incidences of hip fractures and the dynamics of bone and wound healing. Clinical trials and demographic studies have been more widespread than biochemical analyses, and have reported poor prognosis for fracture patients who smoke. Scientific research has elucidated some of the negative impacts of tobacco use and investigations involving several animal models in cellular and humoral analyses have shown damage caused by various toxicological processes. Cessation of the habit perioperatively, therefore, is routinely advised to improve outcomes for patients. The current review describes some of the consequences of tobacco smoking in fracture healing. PMID- 20303895 TI - Perforation of an ileal duplication presenting as an acute abdomen. PMID- 20303896 TI - A simple intraoperative technique to avoid limb length discrepancy in total hip arthroplasty. PMID- 20303898 TI - Re: recurrence after inguinal hernia repair at ten years by open darn, open mesh and TEP - no advantage with mesh. PMID- 20303899 TI - [Light forces and orthodontic displacement: a critical review]. AB - Light or optimal forces are currently the focus of many clinical studies. In the literature, a positive correlation between light forces and speed of displacement is often acknowledged. Now, the consensus is neither total nor scientific and the existence of an optimum force level is still the center of discussion, as witnessed by numerous publications. With the new scientific analysis techniques and the advances made in biological and genetic research, we need to rethink these viewpoints from both the biological and mechanical standpoints since cellular and molecular transformations account for the series of events leading up to damage-free orthodontic displacement. The aim of this paper is to report on recent data regarding the bio-adaptability of teeth and periodontium to orthodontic forces systems in order to enhance our understanding of the physiology and physiopathology involved. Such understanding is a must if we are to optimize our treatment arsenal and achieve greater control of treatment times which are frequently judged excessive. PMID- 20303900 TI - [Measurement of mesiodistal root angulation for panoramic images and the effect of buccolingual root angulation]. AB - Panoramic images were taken from an anatomically correct phantom with three different buccolingual angulations for each tooth (Original, 10 degrees buccal root torque, and 10 degrees lingual root torque). The true mesiodistal angulation of each tooth was determined with a three-dimensional coordinate measurement machine. Each tooth had at least one angle measurement that was statistically different from the other mesiodistal angles with different buccolingual orientations. Roots with buccal root orientations were projected more distally than they were in reality; and the roots lingually positioned were projected more mesially. The canine and premolars in both arches were most affected and the phenomenon was more pronounced in the maxilla than the mandible. Buccolingual orientation changes did not affect the root angulation expression on the incisor area. PMID- 20303901 TI - [The impact of extractions on profile esthetics: a statistical study]. AB - This study assesses and compares the impact of orthodontic treatment with premolar extractions on the profile of the soft tissues in hyper- and normodivergent patients from our Moroccan population which is characterized by a high rate of hyperdivergency. This retrospective study was performed on a sample of 60 adults (30 hyperdivergents and 30 normodivergents). Pre-treatment and end of-treatment headfilms were used to take sagittal and vertical measurements of soft tissue using the Frapier method which takes the Bjork-Nielsen implant line as superimposition landmark. The results of this study show marked improvements on the soft tissues, even though the mean differences are occasionally non-or only slightly significant. In contrast, the vertical dimension has little incidence on the results obtained. The response to treatment of hyperdivergent patients, even when displaying a greater initial esthetic deficit, is similar to that of normodivergents. In certain areas, the improvement was occasionally greater, notably at the soft-tissue pogonion, the mento-labial angle and the naso labial angle. PMID- 20303902 TI - [Diastemas: is retention necessary]. AB - The proposed article is extracted from the author's book entitled "Common Sense Mechanics in Everyday Orthodontics II", published by CSM. In this chapter, the author addresses the biomechanics and treatment of inter-incisal diastemas. The long-term stability of these results is based more on the control of the divergence of the incisal axis and vertical effects of occlusal forces than on the efficiency of the retainer. PMID- 20303903 TI - Incisor position control in lingual orthodontics. AB - The patient requirement for tailor-made individualized orthodontic treatment is met by cutting edge, state-of-the art computer-aided design and manufacturing technology (CAD/CAM), in order to efficiently and smoothly merge the two normally separate processes of bracket fabrication and bracket positioning. Also, the specific approach of the lingual orthodontic specialist using an innovative and effective tool to manage almost every incisor positioning is an absolute key to satisfying the patients' demand. Four clinical cases are shown below with a view to illustrating the precise incisor positioning, as requested by the patients. PMID- 20303904 TI - European College of Orthodontics. Commission on Membership and Tenure. PMID- 20303905 TI - [A novel protocol for hyperdivergent Class II surgery: innovation or breaking a taboo?]. AB - The widespread distribution via Internet of images and even videos showing facial surgery has considerably contributed to our knowledge of orthodontic-surgical treatment. The never-ending increase in the number of patients receiving surgery has given us food for thought and statistics. If we are to progress further, we need to innovative in the area of surgical technique as well as in our clinical and psychological approach to patients. We have endeavoured to move forward from the idea of "straightforward" malocclusion repair to that of "morphofunctional surgery of the face" by emphasizing the esthetic and occlusal outcome. PMID- 20303906 TI - [Impact of the vertical dimension on the occlusal plane inclination in a Moroccan population]. AB - This study was performed in order to investigate the influence of the vertical dimension on the occlusal plane angle. Cephalometric tracing were made from sideview headfilms from a sample of 150 patients consulting at the consultation and treatment center in Rabat, Morocco. This sample group included 60 males and 90 females. The aims of our research were to study statistically the impact of the vertical dimension on the occlusal plane angle and to check the validity of the Wits (Ao-Bo) by evaluating the impact of the vertical dimension on the Wits and by comparing it with the AF-BF value (Ao-Bo/Frankfurt) proposed by Chang. PMID- 20303907 TI - [Miniscrews in orthodontics]. AB - In recent years, miniscrews have come to occupy an ever greater place in orthodontic treatment plans. Today, we now know how to successfully deploy these particularly adaptable anchorage devices. The benefits of miniscrews have led orthodontists to adopt them, all the more so as they do no damage in the event of failure. We present the indications which are more and more evidence-based although these anchorage devices are suitable for use in any situation. We also describe the different surgical and orthodontic stages designed to facilitate the insertion of miniscrews and ensure their success. Several treated clinical cases will illustrate the principles underpinning their use in a variety of clinical settings. PMID- 20303908 TI - [Craniomandibular dysfunction and malocclusions]. AB - INTRODUCTION: For many years, the literature reported the key role of occlusal factors in the development of craniomandibular dysfunctions (CMD). In our study, we investigated the connections between the functional and morphological features of dental occlusion and CMDs in a population of students at the Casablanca Faculty of Dental Medicine, Morocco. MATERIAL AND METHOD: Our study comprised a sample of 142 students from the Casablanca Faculty of Dental Medicine aged between 18 and 30 years. An information card was filled in providing general details, medical history, the clinical examination and an assessment of the orofacial functions. We looked for possible links between CMDs and the various malocclusions. The statistical test used was the Khi2 test under Epi-info 6.0 under MS Dos. RESULTS AND CONCLUSION: There is no connection between craniomandibular dysfunctions and certain malocclusions in the student population at the Casablanca Faculty of Dental Medicine. PMID- 20303909 TI - [Orthodontic partial disimpaction of mandibular third molars prior to surgical extraction]. AB - Odontodysplasia of the third molars is a relatively common anomaly. The frequent complications associated with this disorder very often constitute an indication for extraction of the third molar. This surgical treatment can damage the lower alveolar nerve and/or trigger distal bone loss of the second molar, thus jeopardizing the future status of the periodontium. The author presents two case studies treated exclusively with miniscrews with no dental anchorage in order to achieve partial eruption of the third molar moving it away from the lower alveolar nerve and to avoid unwanted impact on other teeth. Following this procedure, the third molar was extracted without complications. In conclusion, this approach can offer an alternative to surgical treatment alone in cases where the proximity of tooth and nerve poses a significant risk. PMID- 20303910 TI - [Comparison of the effect of paracetamol and ibuprofen on orthodontic pain]. AB - Patients undergoing orthodontic treatment can experience an unpleasant painful sensation. This has been proven by several studies. Controling pain during orthodontic treatment is in the interest of both practitioner and patient. The aim of this study was to compare the effect of ibuprofen and paracetamol on orthodontic pain. To this end, a sample of 56 patients was divided into two groups: Pain levels were assessed using the visual analog scale at 2h, 6h, 24h, day 2, day 3 and day 7 after insertion of the first archwire. Results show that there is no significant difference between ibuprofen and paracetamol regarding control of orthodontic pain except during the first two hours after archwire insertion when paracetamol was observed to be slightly more effective than ibuprofen. Comparison by age and gender revealed no significant differences. Thus, we can conclude that paracetamol and ibuprofen are painkillers of choice in the relief of orthodontically-related pain. PMID- 20303911 TI - [Occlusal plane control in hyperdivergents: regarding one case]. AB - Management of occlusal plane inclination in the sagittal dimension is one of the main concerns of practitioners. Inclination maintenance or correction can condition the success and stability of treatment. By means of a clinical case, we will attempt to discuss the different aspects of management from diagnosis to treatment, bearing in mind the local and regional context. The adopted treatment plan takes into consideration the functional and esthetic issues specific to Moroccan patients without neglecting soft tissue harmony. PMID- 20303912 TI - [French Board of Orthodontics]. PMID- 20303913 TI - The tongue: deglutition, orofacial functions and craniofacial growth. AB - So-called "primary" or "infantile" forms of deglutition, also termed lingual dyspraxia, are treated in different ways by orthodontists using various appliances to correct the condition and are also managed by speech-therapists and physiotherapists. The results obtained are often unstable. We have developed a more holistic approach to this disorder by attempting to grasp the underlying mechanisms in order to achieve more satisfactory correction. By establishing normal salivary deglutition more rapidly, this manual osteopathic technique complements the methods which use voluntary rehabilitation to impress upon the body's physical reflexes the "motor image" of the act to be accomplished. In order to render this article more lively and accessible, we have chosen to let the tongue speak in the first person--which, after all, is only normal! PMID- 20303914 TI - Surgical-orthodontic management of dental impaction. AB - The aim of this study was to assess the management of impacted teeth using surgical-orthodontic techniques at a dental treatment centre in Casablanca and to suggest strategies designed to enhance treatment of dental impaction. MATERIALS AND METHODS: The sample comprised 30 patients represented by their clinical files (mean age: 17 years; standard deviation: 8.141). RESULTS: Impaction most often involved a single tooth (56.7%), generally the upper canine (66%). The location was buccal in 43.3% of cases and generally high (63.3%). Presurgical orthodontic treatment was required in 80 of these cases. A closed eruption technique is reported in 93.1% of cases. Mean treatment duration was 11.4 months. The success rate of the surgical technical technique was 70%. DISCUSSION: A similarity exists between most of the variables studied and findings of other studies published on the same topic. PMID- 20303915 TI - The status of proof in orthodontics. AB - Current orthodontic practice cannot be considered to constitute a discipline entirely based on scientific evidence. Unacceptable methodological flaws tarnish diagnosis and treatment in the majority of medical disciplines. The history and philosophy of medicine give abundant food for thought. At a time when European community bodies are calling for evidence-based medicine, this article issues an invitation to reflect about the facts and conventions in our specialty which are generally acknowledged to be well-founded. This article transposes what contemporary philosophy has to say about medicine in general to the more limited field of orthodontics and reiterates the reservations expressed in the orthodontic literature regarding the methods used to address diagnosis and treatment. PMID- 20303916 TI - Study of the dimensions of the lateral incisors and their involvement in anterior tooth-size discrepancy. AB - Tooth-size discrepancy (TSD), i.e. the disproportion between the size of the maxillary teeth and that of the mandibular teeth, impacts the quality of esthetic and occlusal results in orthodontic treatment. Various studies have shown that, in anterior TSDs, the deficit is most often maxillary and the small size of the upper lateral incisor is incriminated. The present study was performed on a sample of 30 moulds from Moroccan patients displaying an anterior TSD. The differences in the sizes of the upper and lower lateral incisors were compared with a control sample with normal occlusion. The aim of the study was to check the validity of similarity of size between the upper and the lower lateral incisors as a clinical sign of possible anterior TSD. Our results confirmed the efficacy of this rapidly detectable clinical sign in the diagnosis of anterior TSDs. PMID- 20303917 TI - Treatment of the obstructive sleep apnea syndrome in adults by mandibular advancement device: the state of the art. AB - The obstructive sleep apnea syndrome (OSAS) constitutes a non-negligible risk which requires management by specialists of the upper airways. When OSAS is diagnosed, it needs to be treated and different resources are listed. Different forms of treatment can be envisaged: positive pressure ventilation (VCPP), mandibular advancement devices (MAD), and surgery (soft and hard tissues). The authors focus especially the treatments for MAD, outlining their positive and negative impact on ventilation, TMJ, the bony base and interarch relationships. PMID- 20303918 TI - A comparative analysis of angular cephalometric values between CBCT generated lateral cephalograms versus digitized conventional lateral cephalograms. AB - This study compared angular cephalometric values from scanned traditional lateral cephalograms versus CBCT generated slices. Traditional lateral cephalograms (using Orthoceph OC100) and volumetric CBCT imaging (using NewTom 3G Volume Scanner) were taken from 36 patients. Lateral cephalometric analysis using Dolphin 3D was performed on the respective imported radiographic data and ten angular measurements were evaluated. The reliability of measurements was evaluated with an intra-class correlation coefficient (ICC). Paired MANOVA was used to compare differences in measurements between the two image modalities. Inter-rater reliability demonstrated high reliability in 90% of the measurements (ICC >0.8). A high intra-rater reproducibility (ICC >0.8) was demonstrated in all angles. No significant difference in the angular measurements was detected between the two image modalities (paired MANOVA p >0.1, alpha =0.05). A lateral slice from CBCT imaging can be used to perform traditional cephalometric analysis with levels of precision and accuracy comparable to traditional lateral cephalometrics. PMID- 20303919 TI - Corrosion resistance of NiTi in fluoride and acid environments. AB - The aim of our study was to assess in the laboratory the electrochemical behavior of nickel-titanium alloy (NiTi) by simulating the aggressive conditions found in the mouth (notably fluoride and acidity) in order to determine its biocompatibility. The impact of fluoride and pH acid on the corrosion resistance of orthodontic NiTi was studied using classic electrochemical measurement techniques including follow-up over time of the corrosion potential, polarization measurements and impedance spectroscopy. In addition, scanning electron microscopy was used to evaluate the status of the alloy surface before and after immersion in the different media. The results demonstrated the particularly low corrosion resistance of NiTi alloy in the presence of fluorides. In an acidic environment, the alloy showed greater resistance thanks to the passivation phenomenon. The synergistic action of fluoride and ph Acid on NiTi corrosion was not clearly demonstrated. PMID- 20303920 TI - Lingual straight wire method. AB - The mushroom arch-wire is mainly used in lingual orthodontic treatment but the complicated wire bending it requires affects both the treatment results and the time spent at the chair. The author proposes a new lingual straight wire method (LSW) in order to facilitate arch coordination and simplify the mechanics. The attention paid to the set-up model and bracket positioning and bonding plus the use of the new LSW method will also improve patient comfort. PMID- 20303921 TI - Posterior growth and forecasting the development of mandibular third molars. AB - The inter-dependence of overall orthodontic treatment and the development of the third molars requires the entire dentition to be taken into consideration ab initio and for the patient to be fully informed as to the extractions involved. The anatomical conditions in which the development of the wisdom teeth can occur are studied using comparative samples, with and without third molar retention, followed up to the age of 20 years. Posterior growth observed between the beginning of multiband treatment and adulthood amounted to 11/16mm (girls/boys). The initial difference in forecasting the space between the groups with retained third molars and without was slight (5.5mm). However, this difference was maintained throughout the growth period and was sufficient to guide the final choice whether to extract these teeth or allow them to erupt. PMID- 20303922 TI - Lingual orthodontics in the new era treatment according to criteria for occlusion and aesthetics. AB - There has been remarkable progress in the field of orthodontics with the advent of CAD/CAM technology since the beginning of the 21st century. In lingual orthodontics, brackets designed and manufactured with a CAD/CAM system [1] are now available to produce more efficient tooth movement with reduced frictional resistance. The use of implant anchors for absolute anchorage has eliminated the need for excessive tipping of the molars with anchorage bends, which compromises periodontal health, as well as the need for application of heavy extraoral forces, thus providing more reasonable treatment options for both the patient and orthodontist. PMID- 20303923 TI - European College of Orthodontics. Commission on Membership and Tenure. PMID- 20303924 TI - Genetic analyses of Trypanosoma cruzi isolates from naturally infected triatomines and humans in northeastern Brazil. AB - Trypanosoma cruzi genetic diversity was investigated in 25 isolates (vectors and humans) from the semiarid zone of the State of Rio Grande do Norte, Brazil. Molecular markers (3' region of the 24Salpha rRNA; mitochondrial cytochrome oxidase subunit 2 (COII) gene; spliced leader intergenic region (SL-IR) gene; allelic size microsatellite polymorphism) identified 56% TcIII (100% Panstrongyluslutzi; 50% Triatomabrasiliensis); 40% TcII (91.7% humans; 50% T. brasiliensis) and 4% TcI (human). Microsatellite analysis revealed monoclonal and heterozygous patterns on one or more microsatellite loci in 64% of T. cruzi isolates (92.3% triatomines; 33.3% humans) and 36% putative polyclonal populations (66.7% humans; 7.7% triatomines) by loci SCLE10, SCLE11, TcTAT20, TcAAAT6, all belonging to TcII. Identical T. cruzi polyclonal profiles (88.9%) were detected, mostly from humans. The adaptative natural plasticity of TcII and TcIII and their potential for maintaining human infection in T. brasiliensis were confirmed. Intraspecific and phylogenetic T. cruzi diversity in the sylvatic and domestic transmission cycles in this specific region will provide exclusive control strategies. PMID- 20303925 TI - Schistosomiasis in infants and preschool-aged children: Infection in a single Schistosoma haematobium and a mixed S. haematobium-S. mansoni foci of Niger. AB - The burden of schistosomiasis in infants and preschool-aged children and their mothers is poorly known. We carried out a cross-sectional epidemiological survey in two villages in Niger: Falmado is endemic for Schistosoma haematobium only, whereas a mixed S. haematobium-S. mansoni focus has been reported from Diambala. The survey examined 282 children (149 girls, 133 boys, average age: 2.6 years) and 224 mothers (average age: 30.1 years). For S. haematobium diagnosis, two urine samples obtained on consecutive days were subjected to the standard urine filtration method. Additionally, macro- and microhaematuria were determined. The diagnosis of S. mansoni was based on a single stool sample with duplicate Kato Katz thick smears. In Diambala, a standardised, pre-tested questionnaire was administered to mothers, which recorded demographic data, treatment history with anthelminthic drugs, household sanitation and water supply, and bathing practices for their children. Prevalence of egg-patent S. haematobium infections among young children and their mothers was respectively 50.5% and 55.6%, in Falmado, and 60.5% and 72.2% in Diambala. The prevalence of S. mansoni infection in Diambala was 43.8% among children and 52.1% in mothers. Mixed egg-patent infections of S. haematobium and S. mansoni were revealed in 28.6% of the children and 37.3% of the mothers. Questionnaire data showed that 69.8% of the children were accompanied by their mothers to schistosomiasis transmission sites before they were 1 year of age, and that three-quarter of the mothers used water directly drawn from the irrigation canals to wash their children. To conclude, a substantive proportion of children below the age of 5 years had egg-patent schistosomiasis, inclusive of co-infection with S. haematobium and S. mansoni. In the context of schistosomiasis control, more attention should be paid on preschool-aged children and women of childbearing age, so that they can benefit from preventive chemotherapy, which in turn might increase effective coverage of those infected. PMID- 20303926 TI - Synthesis of fatty acids de novo is required for photosynthetic acclimation of Synechocystis sp. PCC 6803 to high temperature. AB - The role of fatty acid synthesis in the acclimation of the photosynthetic machinery to high temperature was investigated in a mutant of the cyanobacterium Synechocystis sp. PCC 6803 that had a lower than wild-type level of enoyl-(acyl carrier-protein) reductase FabI, a key component of the type-II fatty acid synthase system. The mutant exhibited marked impairment in the tolerance and acclimation of cells to high temperature: photoautotrophic growth of the mutant was severely inhibited at 40 degrees C. Moreover, mutant cells were unable to achieve wild-type enhancement of the thermal stability of photosystem II (PSII) when the growth temperature was raised from 25 degrees C to 38 degrees C. Enhancement of the thermal stability of PSII was abolished when wild-type cells were treated with triclosan, a specific inhibitor of FabI, and the enhancement of thermal stability was also blocked in darkness and in the presence of chloramphenicol. Analysis of fatty acids in thylakoid membranes revealed that levels of unsaturated fatty acids did not differ between mutant and wild-type cells, indicating that the saturation of fatty acids in membrane lipids might not be responsible for the enhancement of thermal stability at elevated temperatures. Our observations suggest that the synthesis de novo of fatty acids, as well as proteins, is required for the enhancement of the thermal stability of PSII during the acclimation of Synechocystis cells to high temperature. PMID- 20303927 TI - cAMP-dependent protein kinase regulates post-translational processing and expression of complex I subunits in mammalian cells. AB - Work is presented on the role of cAMP-dependent protein phosphorylation in post translational processing and biosynthesis of complex I subunits in mammalian cell cultures. PKA-mediated phosphorylation of the NDUFS4 subunit of complex I promotes in cell cultures in vivo import/maturation in mitochondria of the precursor of this protein. The import promotion appears to be associated with the observed cAMP-dependent stimulation of the catalytic activity of complex I. These effects of PKA are counteracted by activation of protein phosphatase(s). PKA and the transcription factor CREB play a critical role in the biosynthesis of complex I subunits. CREB phosphorylation, by PKA and/or CaMKs, activates at nuclear and mitochondrial level a transcriptional regulatory cascade which promotes the concerted expression of nuclear and mitochondrial encoded subunits of complex I and other respiratory chain proteins. PMID- 20303928 TI - Interaction of 18-methoxycoronaridine with nicotinic acetylcholine receptors in different conformational states. AB - The interaction of 18-methoxycoronaridine (18-MC) with nicotinic acetylcholine receptors (AChRs) was compared with that for ibogaine and phencyclidine (PCP). The results established that 18-MC: (a) is more potent than ibogaine and PCP inhibiting (+/-)-epibatidine-induced AChR Ca(2+) influx. The potency of 18-MC is increased after longer pre-incubation periods, which is in agreement with the enhancement of [(3)H]cytisine binding to resting but activatable Torpedo AChRs, (b) binds to a single site in the Torpedo AChR with high affinity and inhibits [(3)H]TCP binding to desensitized AChRs in a steric fashion, suggesting the existence of overlapping sites. This is supported by our docking results indicating that 18-MC interacts with a domain located between the serine (position 6') and valine (position 13') rings, and (c) inhibits [(3)H]TCP, [(3)H]ibogaine, and [(3)H]18-MC binding to desensitized AChRs with higher affinity compared to resting AChRs. This can be partially attributed to a slower dissociation rate from the desensitized AChR compared to that from the resting AChR. The enthalpic contribution is more important than the entropic contribution when 18-MC binds to the desensitized AChR compared to that for the resting AChR, and vice versa. Ibogaine analogs inhibit the AChR by interacting with a luminal domain that is shared with PCP, and by inducing desensitization. PMID- 20303929 TI - Analysis of microRNAs induced by Venezuelan equine encephalitis virus infection in mouse brain. AB - MicroRNAs (miRNA) are small RNA (approximately 22nts) molecules that are expressed endogenously in cells and play an important role in regulating gene expression. Recent studies have shown that cellular miRNA plays a very important role in the pathogenesis of viral infection. Venezuelan equine encephalitis virus (VEEV) is an RNA virus and is a member of the genus Alphavirus in the family Togaviridae. VEEV is infectious in aerosol form and is a potential biothreat agent. In this study, we report for the first time that VEEV infection in mice brain causes modulation of miRNA expression. Pathway analyses showed that majority of these miRNAs are involved in the neuronal development and function. Target gene prediction of the modulated miRNAs correlates with our recently reported mRNA expression in VEEV infected mice brain. PMID- 20303930 TI - Stereo-specific synthesis of analogs of nerve agents and their utilization for selection and characterization of paraoxonase (PON1) catalytic scavengers. AB - Fluorogenic organophosphate inhibitors of acetylcholinesterase (AChE) homologous in structure to nerve agents provide useful probes for high throughput screening of mammalian paraoxonase (PON1) libraries generated by directed evolution of an engineered PON1 variant with wild-type like specificity (rePON1). Wt PON1 and rePON1 hydrolyze preferentially the less-toxic R(P) enantiomers of nerve agents and of their fluorogenic surrogates containing the fluorescent leaving group, 3 cyano-7-hydroxy-4-methylcoumarin (CHMC). To increase the sensitivity and reliability of the screening protocol so as to directly select rePON1 clones displaying stereo-preference towards the toxic S(P) enantiomer, and to determine accurately K(m) and k(cat) values for the individual isomers, two approaches were used to obtain the corresponding S(P) and R(P) isomers: (a) stereo-specific synthesis of the O-ethyl, O-n-propyl, and O-i-propyl analogs and (b) enzymic resolution of a racemic mixture of O-cyclohexyl methylphosphonylated CHMC. The configurational assignments of the S(P) and R(P) isomers, as well as their optical purity, were established by X-ray diffraction, reaction with sodium fluoride, hydrolysis by selected rePON1 variants, and inhibition of AChE. The S(P) configuration of the tested surrogates was established for the enantiomer with the more potent anti-AChE activity, with S(P)/R(P) inhibition ratios of 10 100, whereas the R(P) isomers of the O-ethyl and O-n-propyl were hydrolyzed by wt rePON1 about 600- and 70-fold faster, respectively, than the S(P) counterpart. Wt rePON1-induced R(P)/S(P) hydrolysis ratios for the O-cyclohexyl and O-i-propyl analogs are estimated to be >>1000. The various S(P) enantiomers of O-alkyl methylphosphonyl esters of CHMC provide suitable ligands for screening rePON1 libraries, and can expedite identification of variants with enhanced catalytic proficiency towards the toxic nerve agents. PMID- 20303931 TI - Comparison of the Farr radioimmunoassay, 3 commercial enzyme immunoassays and Crithidia luciliae immunofluorescence test for diagnosis and activity assessment of systemic lupus erythematosus. AB - BACKGROUNDS: Among anti-double-strand (ds)DNA antibody assays, Farr radioimmunoassay is decreasingly used because it requires radioactive material and is labor intensive. We evaluated the performance of Farr, three commercial enzyme immunoassays (EIAs) and the Crithidia luciliae immunofluorescence test (CLIFT) in systemic lupus erythematosus (SLE). METHODS: Anti-dsDNA antibodies were determined in 99 SLE patients, 101 healthy subjects, and 53 patients with autoimmune rheumatic diseases. RESULTS: Farr performed better than the 3 EIAs and CLIFT for the diagnosis of SLE at the manufacturer's cut off and at the cut off set to achieve a specificity of 95%. To achieve a similar level of specificity, some EIAs had a decrease in sensitivity which was dramatic for some tests. Farr was also the best at distinguishing patients with quiescent to mildly active disease from patients with more active disease at the cut off value of 93 IU/ml. Using manufacturer's cut off did not allow distinguishing between patients with quiescent and active SLE. CONCLUSIONS: Farr was the best global test to assess the level of anti-dsDNA antibodies for both diagnosis and disease activity evaluation in SLE with adequately determined cut off values. Some EIA had low performances limiting their use in decision-making regarding diagnosis and/or treatment. PMID- 20303932 TI - Maintenance of esterase activity and immunoreactivity after colloidal silver staining of non-denaturing proteins. PMID- 20303933 TI - Thermal degradation of polyethylene glycol 6000 and its effect on the assay of macroprolactin. AB - OBJECTIVES: To study the effectiveness of partially degraded polyethylene glycol 6000 (PEG) as a precipitant for macroprolactin. DESIGN AND METHODS: PEG was heated to 63 degrees C in air for up to 20 days and its effectiveness assessed as a precipitant for sera containing normal prolactin or macroprolactin. Decomposition was studied chemically and with NMR spectroscopy. RESULTS: Thermal degradation was similar to what had occurred over several years of natural degradation. Initially PEG degraded 2-5 days caused excess precipitation of monomeric prolactin (false-positive macroprolactinemia). Samples degraded 18-20 days failed to precipitate macroprolactin, giving false negative results. Two 1H NMR peaks at 4-4.5 ppm were not detectable in undegraded PEG but were after 1 day. Their relative integral increased to 20 days. CONCLUSIONS: Aging of PEG can be accelerated by heating. The suitability of PEG for use in macroprolactin assays can be assessed by the absence of peaks at 4-4.5 ppm by 1H NMR. PMID- 20303934 TI - Presynaptic kainate receptors increase GABAergic neurotransmission in rat periaqueductal gray neurons. AB - Neurons within the periaqueductal gray (PAG) have been implicated in the central regulation of pain signals by affecting the descending inhibitory pathway. Here we report on the functional role of presynaptic kainate receptors within the PAG. Using a conventional whole-cell patch clamp technique, we recorded GABAergic spontaneous miniature inhibitory postsynaptic currents (mIPSCs) from mechanically isolated rat PAG neurons in the presence of 300nM tetrodotoxin and 20microM DL-2 amino-5-phosphonovaleric acid under voltage-clamp conditions. Kainic acid at a 10microM concentration significantly increased the frequency of GABAergic mIPSCs without affecting their amplitude, suggesting that kainic acid acts presynaptically to enhance spontaneous GABA release. The kainic acid-induced increase in mIPSC frequency was completely blocked by CNQX, a selective AMPA/kainate receptor antagonist. While neither AMPA nor NMDA affected GABAergic mIPSC frequency, ATPA, a selective agonist of GluR5-containing kainate receptors, increased GABAergic mIPSC frequency in a concentration-dependent manner. The kainic acid-induced increase in mIPSC frequency was completely suppressed either in the presence of 100microM Cd(2+), a general voltage-dependent Ca(2+) channel (VDCC) blocker, or in the Na(+)-free external solution. These results suggest that presynaptic kainate receptors have a low permeability to Ca(2+), and that their activation elicits a presynaptic depolarization large enough to activate presynaptic VDCCs. Presynaptic kainate receptors on GABAergic nerve terminals appear to modulate GABAergic transmission, and in doing so may play an important role in the regulation of PAG neuron excitability. PMID- 20303935 TI - Mangiferin, a naturally occurring glucoxilxanthone improves long-term object recognition memory in rats. AB - Mangiferin (2-beta-D-glucopyranosyl-1,3,6,7-tetrahydroxyxanthone) is a xanthone widely distributed in higher plants showing antioxidative, antiviral, anticancer, antidiabetic, immunomodulatory, hepatoprotective, and analgesic effects. In the present study, we have investigated the effects of systemic administration of mangiferin on behavioral outcomes of neurological function in normal rats. A single intraperitoneal injection of mangiferin (10, 50, or 100mg/kg body weight) enhanced novel object recognition (NOR) memory when given immediately post training. The administration of mangiferin 6h post-training did not affect NOR memory. There were no significant differences between groups in the total time exploring both objects, indicating that mangiferin did not affect locomotion or motivation. Mangiferin stimulated cell proliferation and induced a significant increase in the supernatant levels of nerve growth factor (NGF) and tumor necrosis factor (TNF)-alpha in vitro in human U138-MG glioblastoma cells. The results indicate that mangiferin enhances recognition memory through a mechanism that might involve an increase in neurotrophin and cytokine levels. PMID- 20303936 TI - The plasma carnitine concentration regulates renal OCTN2 expression and carnitine transport in rats. AB - Previous findings in rats and in human vegetarians suggest that the plasma carnitine concentration and/or carnitine ingestion may influence the renal reabsorption of carnitine. We tested this hypothesis in rats with secondary carnitine deficiency following treatment with N-trimethyl-hydrazine-3-propionate (THP) for 2 weeks and rats treated with excess L-carnitine for 2 weeks. Compared to untreated control rats, treatment with THP was associated with an approximately 70% decrease in plasma carnitine and with a 74% decrease in the skeletal muscle carnitine content. In contrast, treatment with L-carnitine increased plasma carnitine levels by 80% and the skeletal muscle carnitine content by 50%. Treatment with L-carnitine affected neither the activity of carnitine transport into isolated renal brush border membrane vesicles, nor renal mRNA expression of the carnitine transporter OCTN2. In contrast, in carnitine deficient rats, carnitine transport into isolated brush border membrane vesicles was increased 1.9-fold compared to untreated control rats. Similarly, renal mRNA expression of OCTN2 increased by a factor of 1.7 in carnitine deficient rats, whereas OCTN2 mRNA expression remained unchanged in gut, liver or skeletal muscle. Our study supports the hypothesis that a decrease in the carnitine plasma and/or glomerular filtrate concentration increases renal expression and activity of OCTN2. PMID- 20303937 TI - Hypercholesterolemia modifies angiotensin II desensitisation and cross talk between alpha(1)-adrenoceptor and angiotensin AT(1) receptor in rabbit aorta. AB - This study characterised the effect of a hypercholesterolemic diet on the interactions of hormone receptors in the rabbit aorta, both in homologous desensitisation to angiotensin II and cross talk between alpha(1)-adrenoceptors and angiotensin AT(1) receptors. Rabbits were fed either a normal chow or a diet containing 1% cholesterol for 6-7-weeks. Isometric contractions were measured in endothelium-intact or endothelium-removed aortic rings from control and hypercholesterolemic rabbits. Concentration response curves to angiotensin II or noradrenaline incubated with or without prazosin or losartan were performed. In another group, the resting potential was recorded at baseline and following angiotensin II or noradrenaline stimulation. Rabbits fed a hypercholesterolemic diet showed higher plasma levels of total cholesterol and LDL-cholesterol and impaired relaxation to acetylcholine. Homologous desensitisation to angiotensin II was found in endothelium-intact but not in endothelium-removed arteries. Cross talk between alpha(1)-adrenoceptors and angiotensin AT(1) receptors was modified with respect to physiological conditions. In control rabbits, angiotensin II desensitised the noradrenaline response but noradrenaline did not modify the angiotensin II-response. However, in hypercholesterolemic rabbits, angiotensin II sensitised the noradrenaline-response and noradrenaline desensitised the angiotensin II-response. Furthermore, the resting potential remains hyperpolarised after noradrenaline stimulation in hypercholesterolemic rabbits. Modifications in homologous desensitisation to angiotensin II and cross talk between alpha(1)-adrenoceptors and angiotensin AT(1) receptors suggest that hypercholesterolemia induces early tissue dysfunction by altering endothelial and smooth muscle cell regulatory properties. This may be one of the mechanisms by which hypercholesterolemia could be involved in the onset and progression of chronic vascular diseases such as hypertension and arteriosclerosis. PMID- 20303938 TI - Genipin protects lipopolysaccharide-induced apoptotic liver damage in D galactosamine-sensitized mice. AB - This study examined the effects of genipin, isolated from Gardenia jasminoides Ellis, on d-galactosamine (GalN) and lipopolysaccharide (LPS)-induced hepatic apoptosis and liver failure. Mice were given an intraperitoneal injection of genipin (25, 50, 100 and 200mg/kg) 1h before GalN (700mg/kg)/LPS (10microg/kg) administration. The survival rate of the genipin group was significantly higher than that of the control. Genipin markedly reduced the increases in serum aminotransferase activities and lipid peroxidation. The glutathione content decreased in GalN/LPS group, and this decrease was attenuated by genipin. Increases in serum tumor necrosis factor-alpha (TNF-alpha), which were observed in GalN/LPS-treated mice, were significantly reduced by genipin. Genipin attenuated the GalN/LPS-induced apoptosis of hepatocytes, as estimated by the caspase-3 and -8 activity assay, TNF-R1 associated death domain (TRADD) protein measurement and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) method. Moreover, increased cytosolic cytochrome c protein was reduced by genipin. After 3h of GalN/LPS injection, nuclear phosphorylated c-Jun (p-c-Jun) level was significantly increased, whereas it was attenuated by genipin. Also, the increased nuclear level of nuclear factor-kappaB and the decreased cytosolic level of IkappaB-alpha protein were significantly attenuated by genipin. Our results suggest that genipin offers marked hepatoprotection against damage induced by GalN/LPS related with its antioxidative, anti-apoptotic activities, and inhibition of NF-kappaB nuclear translocation and nuclear p-c-Jun expression. PMID- 20303939 TI - Effect of cyclic AMP-elevating agents on airway ciliary beat frequency in central and lateral airways in rat precision-cut lung slices. AB - In patients with chronic obstructive pulmonary disease (COPD), mucociliary clearance of the respiratory tract is impaired due to enhanced mucus secretion and deterioration of normal ciliary activity. We investigated the effects of cyclic AMP-elevating agents with a different mode of action on ciliary beat frequency (CBF) in rat large central and small lateral airways by comparing the phosphodiesterase-4 (PDE4) inhibitors rolipram and roflumilast to the beta(2) adrenoceptor agonist terbutaline and the adenylyl cyclase activator forskolin. Rat precision-cut lung slices were prepared and effects of cyclic AMP-elevating agents on CBF were assessed for up to 4h. In central airways a time- and concentration-dependent increase in CBF was seen for roflumilast (59+/-4%, 1microM, 60min), rolipram (55+/-4%, 1microM, 60min), terbutaline (64+/-8%, 10microM, 60min) and forskolin (55+/-8%, 100microM, 60min). Only roflumilast and rolipram increased CBF in lateral airways, with a similar time course and maximum efficacy (roflumilast 48+/-5%, rolipram 54+/-2%). Incubation of lateral airways with terbutaline (10microM, +11%) or forskolin (100microM, +1%) had negligible effects. As a major novel finding this study reveals that PDE4 inhibitors increased CBF in central as well as in lateral airways, while terbutaline and forskolin affected CBF in proximal airways only. PMID- 20303940 TI - The role of ATP-sensitive potassium channel on acute urinary retention and subsequent catheterization in the rat. AB - We investigated the role of K(ATP) channel on acute urinary retention (AUR) induced bladder dysfunction. Eight-week-old female Sprague-Dawley rats were divided into seven groups: a sham-operated control group, an AUR group, and five AUR groups treated with: two different K(ATP) channel openers namely nicorandil (3 or 10mg/kg), or cromakalim (100 or 300microg/kg), or one K(ATP) channel inhibitor namely glibenclamide (5mg/kg). The drugs were administered 30min before induction of AUR. After the urethra was obstructed with a clip, AUR was induced by intravesical infusion of 2.5ml of saline via cystostomy. Following a 30min obstruction the bladder was allowed to drain with a catheter in place for 60min with real-time monitoring of intravesical pressure and blood flow. After the experimental period, the bladder function was assessed, using organ bath techniques (carbachol and 100mM KCl). AUR increased the intravesical pressure and decreased the blood flow. The subsequent catheterization decreased the intravesical pressure and increased the blood flow. AUR group reduced significantly the contractile responses to both carbachol and KCl compared with the control group. Nicorandil and cromakalim but not glibenclamide prevented the bladder dysfunction after AUR suggesting that K(ATP) channel openers may prevent the bladder dysfunction caused by AUR and subsequent catheterization. PMID- 20303941 TI - Repression of beta-catenin signaling by PPAR gamma ligands. AB - Aberrant activation of the Wnt/beta-catenin signaling pathway plays a crucial role in oncogenesis of various human malignancies. It has been demonstrated that there is a direct interaction between beta-catenin and PPAR gamma. Here we examined the effects of fifteen reported PPAR ligands in a reporter gene assay that is dependent on beta-catenin activation of TCF/LEF transcription factors; only the thiazolidinedione PPAR gamma agonists troglitazone, rosiglitazone and pioglitazone, and a non-thiazolidinedione PPAR gamma activator GW1929 inhibited beta-catenin-induced transcription in a PPAR gamma dependent fashion. The results from mammalian one-hybrid experiments showed that functional PPAR gamma was necessary for ligand-dependent inhibition of beta-catenin transactivation. However, a PPAR gamma activator Fmoc-Leu could not repress beta-catenin-mediated signaling and its transactivation activity. These results indicate that activation of PPAR gamma is necessary, but not sufficient, for the beta-catenin antagonistic activity of a PPAR gamma agonist, and that the inhibitory compounds interfere directly with beta-catenin transactivation activity. PMID- 20303942 TI - The point mutation gamma 2F77I changes the potency and efficacy of benzodiazepine site ligands in different GABAA receptor subtypes. AB - Benzodiazepine site agonists or inverse agonists enhance or reduce gamma aminobutyric acid(A) (GABA(A)) receptor-mediated inhibition of neurons, respectively. Recently, it was demonstrated that the point mutation gamma 2F77I causes a drastic change in the affinity of a variety of benzodiazepine agonists or inverse agonists in receptor binding studies. Here we investigated the potency and efficacy of 10 benzodiazepine site ligands from 6 structural classes in wild type and gamma 2F77I point mutated recombinant GABA(A) receptors composed of alpha 1 beta 3 gamma 2, alpha 2 beta 3 gamma 2, alpha 3 beta 3 gamma 2, alpha 4 beta 3 gamma 2, alpha 5 beta 3 gamma 2, and alpha 6 beta 3 gamma 2 subunits. Results indicate that the effects of the benzodiazepine site ligands zolpidem, zopiclone, Cl218872, L-655,708 and DMCM were nearly completely eliminated in all mutated receptors up to a 1 microM concentration. The effects of bretazenil, Ro15 1788 or abecarnil were eliminated in some, but not all mutated receptors, suggesting that the gamma 2F77I mutation differentially influences the actions of these ligands in different receptor subtypes. In addition, this point mutation also influences the efficacy of diazepam for enhancing GABA-induced chloride flux, suggesting that the amino acid residue gamma 2F77 might also be involved in the transduction of the effect of benzodiazepines from binding to gating. The application of these drugs in a novel mouse model is discussed. PMID- 20303943 TI - Effects of chronic systemic administration of the GABA(B) receptor agonist baclofen on food intake and body weight in rats. AB - The effects of daily administration of physiological saline of baclofen (1 and 4mg/kg, i.p.) for 27 days were investigated on food intake and body weight in non deprived rats in Experiment 1. Baclofen (1 and 4mg/kg) significantly increased daily short-term food intake when measured at 30min (F((2,15))=11.011, P<0.01) and 90min (F((2,15))=7.3801, P<0.01) over the 27 day experimental period.. Tolerance did not develop to the short-term hyperphagic effects of baclofen. Baclofen (1mg/kg) had no significant effects on body weight gain of the rats compared with controls. By contrast, baclofen (4mg/kg) significantly (P<0.05) decreased the body weight gain of the animals. In Experiment 2, the effect of daily administration of baclofen (4mg/kg, i.p.) for 24 days was investigated on 24h food intake in rats measured after the first, eight, fifteenth and twenty second injections. The 24h food intake of the animals was not significantly different from those of control rats on any of the measurement days (F((1,14))=1.602, ns). However, the body weight gain of the rats chronically treated with baclofen (4mg/kg) was significantly reduced. (F((1,14))=14.011, P<0.01). The observations that chronic administration of baclofen (4mg/kg) stimulates short-term food intake without affecting long term (24h) feeding, but decreases body weight gain, suggest that baclofen may act through different mechanisms to influence food intake and body weight. PMID- 20303944 TI - Effect of endothelin-A receptor antagonist on mu, delta and kappa opioid receptor mediated antinociception in mice. AB - We have previously shown the involvement of central endothelin (ET) mechanisms in morphine analgesia and tolerance. Here we investigated the interaction of centrally administered endothelin ET(A) receptor antagonist, BMS182874, with DAMGO (micro opioid receptor agonist), SNC80 (delta opioid receptor agonist), U50,488H (kappa opioid receptor agonist), and oxycodone (micro and kappa opioid receptor agonist) towards antinociception, tolerance to antinociception and body temperature. Antinociception was determined using tail-flick latency method. BMS182874 (50microg, i.c.v.) treatment alone did not produce analgesia or change in body temperature. However, BMS182874 significantly enhanced antinociception response of DAMGO (66.75%), SNC80 (62.40%), U50,488H (55.38%), and oxycodone (61.72%). Chronic treatment with DAMGO, SNC80, U50,488H or oxycodone, induced tolerance to antinociception. Treatment with BMS182874 restored antinociceptive effect in mice that were tolerant to DAMGO, SNC80, U50,488H as well as oxycodone. Antinociceptive response of DAMGO, SNC80, U50,488H, and oxycodone in tolerant mice treated with BMS182874 was significantly higher (44.55%, 37.48%, 43.02%, and 56.08%, respectively) compared to tolerant mice treated with vehicle. Body temperature decreased with DAMGO, SNC80, U50,488H, and oxycodone; tolerance did not develop to hypothermic effect and BMS182874 did not affect DAMGO, SNC80, U50,488H, or oxycodone induced changes in body temperature. Opioid-antagonist naloxone, completely blocked antinociceptive effect of DAMGO, SNC80, U50,488H or oxycodone and potentiation of antinociception by BMS182874. It is concluded that BMS182874 potentiated antinociception and restored antinociceptive effect in mice tolerant to micro, delta and kappa selective, as well as a non-selective opioid receptor agonist. Therefore, endothelin ET(A) receptor antagonists could be useful in the restoration of antinociceptive effect during tolerance to opiates. PMID- 20303945 TI - Resveratrol, obesity and diabetes. AB - Resveratrol belongs to the large group of biologically active substances found in plants. This compound is classified as phytoestrogen because of its ability to interact with estrogen receptor. Numerous beneficial effects of resveratrol described in the literature involve cardioprotective, anti-cancer, anti inflammatory and antioxidant action. Recently, this broad spectrum of effects is enlarged by new data demonstrating a great potency of this compound in relation to obesity and diabetes. It is well established that resveratrol exerts beneficial effects in rodents fed a high-calorie diet. In some studies, resveratrol was reported to reduce body weight and adiposity in obese animals. The action of this compound involves favourable changes in gene expressions and in enzyme activities. The accumulating evidence also indicates the benefits of resveratrol in diabetes and diabetic complications. It is known that resveratrol affects insulin secretion and blood insulin concentration. In animals with hyperinsulinemia, resveratrol was found to reduce blood insulin. Moreover, numerous data indicate that in diabetic rats, resveratrol is able to reduce hyperglycemia. The mechanism of resveratrol's action is complex and is demonstrated to involve both insulin-dependent and insulin-independent effects. These data point to the potential possibility of use of resveratrol in preventing and/or treating both obesity and diabetes. PMID- 20303946 TI - Protective effect of all-trans retinoic acid on NMDA-induced neuronal cell death in rat retina. AB - We histologically examined the effects of all-trans retinoic acid (ATRA) on neuronal injury induced by intravitreous injection of N-methyl-d-aspartic acid (NMDA) (200nmol/eye). Treatment with ATRA for 7 days (15mg/kg for the first two days and 10mg/kg for the following five days, p.o.) reduced the decrease of cell number in the ganglion cell layer and the inner nuclear layer 7 days after NMDA injection. TUNEL staining 6h after NMDA injection showed that treatment with ATRA (15mg/kg, p.o.) 1h prior to NMDA injection reduced the number of apoptotic cells in the ganglion cell layer and inner nuclear layer. The anti-apoptotic effect of ATRA was vanished by intravitreous injection of U0126, an extracellular signal regulated kinase/mitogen-activated protein kinase kinase inhibitor (1nmol/eye). These results suggest that ATRA has a protective effect, which is medicated by extracellular signal-regulated kinase pathway, on NMDA-induced apoptosis in the rat retina. ATRA may be useful as a therapeutic drug against retinal diseases that cause glutamate neurotoxicity. PMID- 20303947 TI - Heme oxygenase-1 and carbon monoxide promote neovascularization after myocardial infarction by modulating the expression of HIF-1alpha, SDF-1alpha and VEGF-B. AB - Heme oxygenase-1 (HO-1), a known cytoprotective enzyme implicated also in the cell cycle regulation and angiogenesis, exerts many of its beneficial effects through carbon monoxide (CO). We studied the roles of HO-1 and CO in cardiac regeneration after myocardial infarction. Prior to coronary artery ligation, male Wistar rats were given either cobolt protoporphyrin IX to induce HO-1 or CO-donor methylene chloride. Cardiac regeneration was assessed by immunohistochemistry and confocal microscopy. CO significantly increased the accumulation of c-kit+ stem/progenitor cells into the infarct area and induced formation of new coronary arteries by promoting a substantial differentiation of c-kit+ cells into vascular smooth muscle cells (c-kit+/GATA6+ cells). Furthermore, CO increased proliferation of cardiomyocytes in the infarct border area at 4weeks post infarction. This suggests proliferation of newly formed cardiomyocytes derived from c-kit+ cells as 10% of c-kit+ cells expressed early cardiac marker Nkx2.5. Increased expression of hypoxia-inducible factor-1alpha (HIF-1alpha), stromal cell derived factor-1alpha (SDF-1alpha) and vascular endothelial growth factor-B (VEGF-B) were found in the infarct areas of CO-donor pretreated hearts suggesting that these factors potentially promoted the migration of c-kit+ cells into the infarct area and subsequent vasculogenesis and myocardial regeneration by CO. HO 1 increased both capillary and vascular densities, while only a small increase of c-kit+ cells was found. HO-1 upregulated SDF-1alpha, but did not have effect on HIF-1alpha and VEGF-B. In conclusion, HO-1 and CO have differential roles and mechanisms of action in cardiac regeneration. Modulation of the HO-1/CO axis may provide a novel tool for the repair of cardiac injury. PMID- 20303948 TI - The timing of administration, dose dependence and efficacy of dopa decarboxylase inhibitors on the reversal of motor disability produced by L-DOPA in the MPTP treated common marmoset. AB - Dopa decarboxylase inhibitors are routinely used to potentiate the effects of L DOPA in the treatment of Parkinson's disease. However, neither in clinical use nor in experimental models of Parkinson's disease have the timing and dose of dopa decarboxylase inhibitors been thoroughly explored. We now report on the choice of dopa decarboxylase inhibitors, dose and the time of dosing relationships of carbidopa, benserazide and L-alpha-methyl dopa (L-AMD) in potentiating the effects of L-DOPA in the 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine (MPTP)-treated common marmoset. Pre-treatment with benserazide for up to 3h did not alter the motor response to L-DOPA compared to simultaneous administration with L-DOPA. There was some evidence of a relationship between carbidopa and benserazide dose and increased locomotor activity and the reversal of motor disability. But in general, commonly used dose levels of dopa decarboxylase inhibitors appeared to produce a maximal motor response to L-DOPA. In contrast, dyskinesia intensity and duration continued to increase with both carbidopa and benserazide dose. The novel dopa decarboxylase inhibitor, L-AMD, increased locomotor activity and improved motor disability to the same extent as carbidopa or benserazide but importantly this was accompanied by significantly less dyskinesia. This study shows that currently, dopa decarboxylase inhibitors may be routinely employed in the MPTP-treated primate at doses which are higher than those necessary to produce a maximal potentiation of the anti-parkinsonian effect of L-DOPA. This may lead to excessive expression of dyskinesia in this model of Parkinson's disease and attention should be given to the dose regimens currently employed. PMID- 20303949 TI - Oral administration of ethanol with aspirin increases the concentration of salicylic acid in plasma and organs, especially the brain, in mice. AB - Aspirin (acetylsalicylic acid) has been widely used as an over-the-counter drug to relieve pain throughout the world. In suicide attempts, aspirin is one of the most common drugs taken in large quantities. The concentration of salicylic acid shows a low-level distribution in the mouse brain, a site that may be critical regarding the expression of symptoms (e.g. hyperpnea, coma, convulsion and tremor) during acute aspirin toxicity. Therefore, it was suggested that sensitivity to salicylic acid concerning acute toxicity was higher in the brain than in other organs. Moreover, it is thought that it is common for aspirin and ethanol to be ingested at the same time. Therefore, the present study was designed to investigate the influence of ethanol on the distribution of salicylic acid, which is a primary metabolite of aspirin, and its related metabolite, salicyluric acid. The oral co-administration of aspirin (0.5g/kg) and ethanol (2.5g/kg; 10ml/kg of 25% (w/v)) enhanced the concentrations of salicylic acid in the plasma and organs, especially in the brain, compared with the aspirin alone treated group. On the other hand, ethanol did not influence the concentrations of salicyluric acid in the plasma and kidney compared with the aspirin alone-treated group. These results suggest that ethanol enhances aspirin absorption from the gastrointestinal tract but has no influence on its metabolism. Thus, it is dangerous to ingest the alcohol and aspirin at the same time, as this may exacerbate the acute toxicity of aspirin. PMID- 20303950 TI - 12-Lipoxygenase and the regulation of hypoxia-inducible factor in prostate cancer cells. AB - 12-Lipoxygenase, an arachidonic acid metabolizing enzyme of the lipoxygenase pathway, has been implicated as a major factor in promoting prostate cancer progression and metastasis. The ability of 12-LOX to aggravate the disease was linked to its proangiogenic role. Recent studies clearly demonstrated that 12-LOX enhances the expression and secretion of the angiogenic factor, vascular endothelial growth factor (VEGF) thus providing a direct link between this enzyme and its angiogenic properties. In the present study we have investigated the relationship between 12-LOX and hypoxia inducible factor-1alpha (HIF-1alpha), a transcription factor involved in the regulation of VEGF expression under hypoxic conditions in solid tumors. Our findings have revealed that HIF-1 is one of the target transcription factors regulated by 12-LOX and 12(S)-HETE, in hypoxic tumor cells of the prostate. Regulation of HIF-1alpha by 12-LOX adds to the complexity of pathways mediated by this enzyme in promoting prostate cancer angiogenesis and metastasis. We have evidence that 12-LOX increases the protein level, mRNA, and functional activity of HIF-1alpha under hypoxic conditions, one of the mechanisms by which it upregulates VEGF secretion and activity. PMID- 20303951 TI - Kaiso regulates Znf131-mediated transcriptional activation. AB - Kaiso is a dual-specificity POZ-ZF transcription factor that regulates gene expression by binding to sequence-specific Kaiso binding sites (KBS) or methyl CpG dinucleotide pairs. Kaiso was first identified as a binding partner for the epithelial cell adhesion regulator p120(ctn). The p120(ctn)/Kaiso interaction is reminiscent of the beta-catenin/TCF interaction and several studies have suggested that Kaiso is a negative regulator of the Wnt/beta-catenin TCF signaling pathway. To gain further insight into Kaiso's function, we performed a yeast two-hybrid screen using the Kaiso POZ domain as bait. This screen identified the POZ-ZF protein, Znf131, as a Kaiso-specific binding partner. GST pull-down assays confirmed that the interaction is mediated via the POZ domain of each protein, and co-immunoprecipitation experiments further supported an in vivo Kaiso-Znf131 interaction. Using a Cyclic Amplification and Selection of Targets (CAST) approach, we identified the 12-base pair DNA palindrome sequence GTCGCR (X)(n)-YGCGAC as a potential Znf131 binding element (ZBE). In vitro studies using electrophoretic mobility shift assay (EMSA) demonstrated that Znf131 binds the ZBE via its zinc finger domain. Znf131 DNA-binding specificity was confirmed using competition assays and ZBE mutational analyses. An artificial promoter reporter construct containing four tandem copies of the ZBE was constructed and used to assess Znf131 transcriptional properties. We observed dose-dependent transcriptional activation of this artificial promoter-reporter by Znf131 in both epithelial and fibroblast cells, suggesting that Znf131 is a transcriptional activator. Kaiso overexpression significantly decreased the Znf131-mediated transcriptional activation, and interestingly, co-expression of the Kaiso specific interaction partner p120(ctn) relieved Kaiso's inhibition of Znf131 mediated transcriptional activation. These findings indicate that Znf131 is a transcriptional activator, a less common function of POZ-ZF proteins, that is negatively regulated by its heterodimerization partner Kaiso. PMID- 20303953 TI - Leishmania donovani s.l.: evaluation of the proliferation potential of promastigotes using CFSE staining and flow cytometry. AB - Leishmania infantum causes visceral leishmaniasis in all countries in the Mediterranean basin. It uses Phlebotomine sandflies as vectors where the promastigote stage develops, reproduces and becomes infective. Therefore the reproductive power of the promastigotes determines the inoculum size of the isolate. Ten Leishmania strains from Cyprus: two Leishmania donovani and eight L. infantum were used to study the proliferation capacity of the promastigotes. Population increase during a 6-day culture period was assessed quantitatively, by haematocytometer enumeration, and qualitatively by following the division history of each population during the same period by CFSE staining and flow cytometry. The strains exhibited different proliferation rates with L. infantum showing higher multiplication rates than L. donovani. These differences may represent their fitness capabilities and their ability to synchronize the multiplication activity of individual members in the population for the production of a sizeable inoculum in time for the vector's blood meal. PMID- 20303952 TI - Estrogen effects on pain sensitivity and neuropeptide expression in rat sensory neurons. AB - While a number of chronic pain conditions are much more prevalent in women than men, the role of estrogen in regulating nociception remains unclear. Estrogen receptors (ER) are known to be expressed in various parts of the nociceptive pathway, including in the small-sized primary sensory neurons of the dorsal root ganglion (DRG). This study evaluated the effects of long term estrogen replacement on pain sensitivity and neuropeptide expression in the DRG of female Sprague Dawley rats. The goal was to evaluate whether estrogen modulates nociceptive neuropeptides in the DRG in a manner consistent with its effects on pain sensitivity. Our results show that long term (28 days) ovariectomy (ovx) of adult rats induces a profound thermal and mechanical hyperalgesia of the hindpaw and tail compared to ovariectomized animals that were continuously estrogen treated (ovx+E). Significant changes in the expression of two neuropeptides, substance P (SP) and calcitonin gene-related peptide (CGRP), were observed using immunocytochemistry and in situ hybridization (ISH) in the small lumbar DRG neurons which contain ER. CGRP and SP were differentially regulated by estrogen, with SP showing a significant downregulation at both the peptide and mRNA levels while CGRP and its mRNA were increased in the DRG of estrogen-treated animals. We also evaluated the development of mechanical allodynia after partial sciatic nerve injury and found that both ovx and ovx+E animals developed significant allodynia within a week of the partial nerve injury, which continued for at least one month. The estrogen-treated animals showed a partial amelioration of the extent of the allodynia at 2 weeks post injury. Overall, the results suggest that estrogen has significant anti-nociceptive actions that can be directly correlated with changes in expression of two peptides in the small nociceptive ERalpha expressing neurons of the DRG. PMID- 20303954 TI - Protection against murine intestinal amoebiasis induced by oral immunization with the 29 kDa antigen of Entamoeba histolytica and cholera toxin. AB - Entamoeba histolytica antigens recognized by salivary IgA from infected patients include the 29 kDa antigen (Eh29), an alkyl hydroperoxide reductase. Here, we investigate the potential of recombinant Eh29 and an Eh29-cholera toxin subunit B (CTxB) fusion protein to confer protection against intestinal amoebiasis after oral immunization. The purified Eh29-CTxB fusion retained the critical ability to bind ganglioside GM(1), as determined by ELISA. Oral immunization of C3H/HeJ mice with Eh29 administered in combination with a subclinical dose of whole cholera toxin, but not as an Eh29-CTxB fusion, induced elevated levels of intestinal IgA and serum IgG anti-Eh29 antibodies that inhibited trophozoites adherence to MDCK cell monolayers. The 80% of immunized mice seen to develop IgA and IgG immune responses showed no evidence of infection in tissue sections harvested following intracecal challenge with virulent E. histolytica trophozoites. These results suggest that Eh29 is capable of inducing protective anti-amoebic immune responses in mice following oral immunization and could be used in the development of oral vaccines against amoebiasis. PMID- 20303955 TI - The immunopathogenesis of Entamoeba histolytica. AB - Amebiasis is the disease caused by the enteric dwelling protozoan parasite Entamoeba histolytica. The WHO considers amebiasis as one of the major health problems in developing countries; it is surpassed by only malaria and schistosomiasis for death caused by parasitic infection. E. histolytica primarily lives in the colon as a harmless commensal, but is capable of causing devastating dysentery, colitis and liver abscess. What triggers the switch to a pathogenic phenotype and the onset of disease is unknown. We are becoming increasingly aware of the complexity of the host-parasite interaction. During chronic stages of amebiasis, the host develops an immune response that is incapable of eliminating tissue resident parasites, while the parasite actively immunosuppresses the host. However, most individuals with symptomatic infections succumb only to an episode of dysentery. Why most halt invasion and a minority progress to chronic disease remains poorly understood. This review presents a current understanding of the immune processes that shape the outcome of E. histolytica infections during its different stages. PMID- 20303956 TI - Folded-unfolded cross-predictions and protein evolution: the case study of coiled coils. AB - Here we report a thorough analysis of cross-predictions between coiled-coil and disordered protein segments using various prediction algorithms for both sequence classes. Coiled-coils are often predicted to be unstructured, consistent with their obligate multimeric nature, whereas reverse cross-predictions are rare due to the regularity of coiled-coil sequences. We propose the simultaneous use of the programs Coils and IUPred to achieve acceptable prediction accuracy and minimize the extent of cross-predictions. The relevance of observed cross predictions might be that disordered sequences can adopt coiled-coil conformation relatively easily during protein evolution. PMID- 20303957 TI - The FHA domain of OdhI interacts with the carboxyterminal 2-oxoglutarate dehydrogenase domain of OdhA in Corynebacterium glutamicum. AB - In Corynebacterium glutamicum, the unphosphorylated 15-kDa OdhI protein inhibits the activity of the 2-oxoglutarate dehydrogenase complex (ODHc) by binding to OdhA, which in corynebacteria and mycobacteria is a large fusion protein with two major domains exhibiting structural features of E1o and E2 proteins. Using copurification and surface plasmon resonance experiments with different OdhI and OdhA length variants it was shown that the entire forkhead-associated (FHA) domain of OdhI and the C-terminal dehydrogenase domain of OdhA are required for interaction. The FHA domain was also sufficient for inhibition of ODHc activity. Phosphorylated OdhI was binding-incompetent and did not inhibit ODHc activity. PMID- 20303958 TI - Imaging of organelles by electron microscopy reveals protein-protein interactions in mitochondria and chloroplasts. AB - Ongoing progress in electron microscopy (EM) offers now an opening to visualize cells at the nanoscale by cryo-electron tomography (ET). Large protein complexes can be resolved at near-atomic resolution by single particle averaging. Some examples from mitochondria and chloroplasts illustrate the possibilities with an emphasis on the membrane organization. Cryo-ET performed on non-chemically fixed, unstained, ice-embedded material can visualize specific large membrane protein complexes. In combination with averaging methods, 3D structures were calculated of mitochondrial ATP synthase at 6 nm resolution and of chloroplast photosystem II at 3.5 nm. PMID- 20303959 TI - Decreased GLT-1 and increased SOD1 and HO-1 expression in astrocytes contribute to lumbar spinal cord vulnerability of SOD1-G93A transgenic mice. AB - The SOD1-G93A transgenic mouse is a widely used ALS model, but the death of lower motor neurons is the hallmark. Here, we show that the SOD1-G93A transgene and HO 1 are preferentially over-expressed in the lumbar spinal cord, particularly in the activated astrocytes of the transgenic mice. We also show down-regulation of GLT-1 in spite of the proliferating astrocytes. However, GLT-1, SOD1-G93A transgene and HO-1 expression were not obviously changed in the motor cortex. Our data link spinal cord vulnerability to relatively decreased expression of GLT-1, and high expression of the transgene and HO-1 in astrocytes in SOD1-G93A transgenic mice. PMID- 20303960 TI - Lipid droplets: a dynamic organelle moves into focus. AB - Lipid droplets (LDs) were perceived as static storage deposits, which passively participate in the energy homeostasis of both cells and entire organisms. However, this view has changed recently after the realization of a complex and highly dynamic LD proteome. The proteome contains key components of the fat mobilization system and proteins that suggest LD interactions with a variety of cell organelles, including the endoplasmic reticulum, mitochondria and peroxisomes. The study of LD cell biology, including cross-talk with other organelles, the trafficking of LDs in the cell and regulatory events involving the LD coat proteins is now on the verge of leaving its infancy and unfolds that LDs are highly dynamic cellular organelles. PMID- 20303961 TI - Separation of heteromeric potassium channel Kcv towards probing subunit composition-regulated ion permeation and gating. AB - The chlorella virus-encoded Kcv can form a homo-tetrameric potassium channel in lipid membranes. This miniature peptide can be synthesized in vitro, and the tetramer purified from the SDS-polyacrylamide gel retains the K(+) channel functionality. Combining this capability with the mass-tagging method, we propose a simple, straightforward approach that can generically manipulate individual subunits in the tetramer, thereby enabling the detection of contribution from individual subunits to the channel functions. Using this approach, we showed that the structural change in the selectivity filter from only one subunit is sufficient to cause permanent channel inactivation ("all-or-none" mechanism), whereas the mutation near the extracellular entrance additively modifies the ion permeation with the number of mutant subunits in the tetramer ("additive" mechanism). PMID- 20303962 TI - Site-directed mutagenesis and structural modeling of Coq10p indicate the presence of a tunnel for coenzyme Q6 binding. AB - Coq10p is a protein required for coenzyme Q function, but its specific role is still unknown. It is a member of the START domain superfamily that contains a hydrophobic tunnel implicated in the binding of lipophilic molecules. We used site-directed mutagenesis, statistical coupling analysis and molecular modeling to probe structural determinants in the Coq10p putative tunnel. Four point mutations were generated (coq10-K50E, coq10-L96S, coq10-E105K and coq10-K162D) and their biochemical properties analysed, as well as structural consequences. Our results show that all mutations impaired Coq10p function and together with molecular modeling indicate an important role for the Coq10p putative tunnel. PMID- 20303964 TI - Defective interleukin-10 signaling in human inflammatory bowel disease. PMID- 20303965 TI - Do side-by-side anastomoses decrease the risk of recurrence in Crohn's disease? PMID- 20303966 TI - Optimizing care of hereditary hemorrhagic telangiectasia. PMID- 20303967 TI - Aspirin use and survival following colorectal cancer diagnosis: another favorable and promising meta-effect of an old drug. PMID- 20303968 TI - Cytochrome P450 aromatases: Impact on gonadal development, recrudescence and effect of hCG in the catfish, Clarias gariepinus. AB - Present study analyzed the importance of two forms of aromatases during ovarian development and recrudescence of north African/air-breathing catfish. We cloned both CYP19A1 (1941bp; ovarian form) and CYP19A2 (1786bp; brain form), which showed 47% homology between the two forms. Characterization of encoded proteins in non-steroidogenic COS-7 cells illustrated that both isoforms efficiently catalyzed the aromatization reaction by producing estradiol-17beta (E(2)) from testosterone. Tissue distribution pattern revealed preferential expression of CYP19A2 in brain while CYP19A1 predominated in ovary with trace amounts detected in other tissues including brain. Relative real-time PCR analysis revealed high transcript levels of both isoforms in the prespawning phase of ovarian cycle, which is in accordance with serum E(2) level. Aromatase activity in brain was comparatively lower than ovary, indicating the predominant requirement of aromatase in ovary. Ontogeny studies displayed sexual dimorphism, with early expression of CYP19A1 and CYP19A2 in ovary and brain, respectively. Phase dependent rise of expression and enzyme activity of aromatase after hCG treatment revealed the stimulatory role of gonadotropin during preparatory and prespawning phases, preferentially to promote vitellogenesis. Lack of influence of hCG treatment during spawning phase endorses it further. A good correlation of expression, enzyme activity and serum E(2) levels suggests a crucial role of CYP19A1 during ovarian differentiation and ovarian cycle of catfish. Likewise, CYP19A2 might also be involved in these processes either indirectly or directly. PMID- 20303969 TI - Insulin down-regulates the Na+/K+ ATPase in enterocytes but increases intestinal glucose absorption. AB - The effect of insulin on [(14)C] 3-O-methyl-d-glucose (3OMG) absorption in the rat jejunum was studied using an in situ perfusion technique. Insulin increased apical glucose entry into the cells and decreased intestinal retention suggesting that serosal glucose transport was enhanced by the hormone. This enhanced uptake was ascribed to an increase in the expression of glucose transporters as confirmed by Western blot analysis and not to a higher sodium gradient, since insulin reduced the activity and protein expression of the Na(+)/K(+) ATPase. To separate the glycemic from the insulinemic effect on glucose transport, the effect of the hormone was investigated in vitro using cultured Caco-2 cells. The cells also showed an increase in [(14)C] 3OMG uptake and intracellular glucose levels when treated with insulin and a lower Na(+)/K(+) ATPase activity. Phloretin, an inhibitor of GLUT2 was used to determine if these transporters are targeted by the hormone. The results showed that the effect of insulin on glucose uptake and intracellular glucose was still enhanced in presence of phloretin. Considering the inhibitory effect of the hormone on the Na(+)/K(+) ATPase, it was concluded that insulin acts by increasing the number of glucose transporters, a hypothesis that was confirmed by Western blot analysis. PMID- 20303970 TI - The many facets of sex and drugs. PMID- 20303971 TI - Detection and quantification of Panton-Valentine leukocidin in Staphylococcus aureus cultures by ELISA and Western blotting: diethylpyrocarbonate inhibits binding of protein A to IgG. AB - Enzyme-linked immunosorbent assay (ELISA) and Western blotting are common techniques used to detect and quantify proteins in Staphylococcus aureus culture supernatants, such as Panton-Valentine leukocidin (PVL). However, protein A (Spa) secreted by most S. aureus strains may interfere with these assays by binding to the capturing and detecting antibodies. Here, we have shown that the addition of diethylpyrocarbonate (DEPC) inhibits the binding of Spa to rabbit anti-PVL used as the capturing antibody in ELISA. In Western blotting, the presence of DEPC prevented the binding of detecting antibody to Spa. These modified ELISA and Western blot techniques should prove useful for detecting and quantifying proteins in S. aureus culture supernatants. PMID- 20303972 TI - Rhythmic behaviour and pattern-generating circuits in the locust: key concepts and recent updates. AB - There is growing recognition that rhythmic activity patterns are widespread in our brain and play an important role in all aspects of the functioning of our nervous system, from sensory integration to central processing and motor control. The study of the unique properties that enable central circuits to generate their rhythmic output in the absence of any patterned, sensory or descending, inputs, has been very rewarding in the relatively simple invertebrate preparations. The locust, specifically, is a remarkable example of an organism in which central pattern generator (CPG) networks have been suggested and studied in practically all aspects of their behaviour. Here we present an updated overview of the various rhythmic behaviours in the locust and aspects of their neural control. We focus on the fundamental concepts of multifunctional neuronal circuits, neural centre interactions and neuromodulation of CPG networks. We are certain that the very broad and solid knowledge base of locust rhythmic behaviour and pattern generating circuits will continue to expand and further contribute to our understanding of the principles behind the functioning of the nervous system and, indeed, the brain. PMID- 20303973 TI - Ecdysone and the cell cycle: investigations in a mosquito cell line. AB - Cell lines provide a tool for investigating basic biological processes that underlie the complex interactions among the tissues and organs of an intact organism. We compare the evolution of insect and mammalian populations as they progress from diploid cell strains to continuous cell lines, and review the history of the well-characterized Aedes albopictus mosquito cell line, C7-10. Like Kc and S3 cells from Drosophila melanogaster, C7-10 cells are sensitive to the insect steroid hormone, 20-hydroxyecdysone (20E), and express 20E-inducible proteins as well as the EcR and USP components of the ecdysteroid receptor. The decrease in growth associated with 20E treatment results in an accumulation of cells in the G1 phase of the cycle, and a concomitant decrease in levels of cyclin A. In contrast, 20E induces a G2 arrest in a well-studied imaginal disc cell line from the moth, Plodia interpunctella. We hypothesize that 20E-mediated events associated with molting and metamorphosis include effects on regulatory proteins that modulate the mitotic cell cycle and that differences between the 20E response in diverse insect cell lines reflect an interplay between classical receptor-mediated effects on gene expression and non-classical effects on signaling pathways similar to those recently described for the vertebrate steroid hormone, estrogen. PMID- 20303974 TI - Dopamine enhances locomotor activity for mating in male honeybees (Apis mellifera L.). AB - Dopamine plays multiple roles in the regulation of reproduction in female honeybees where it appears to act independently of juvenile hormone (JH). In males the role of dopamine and its relationship to JH control have not been elucidated. In the present study we determined hemolymph levels of dopamine and its metabolite (N-acetyldopamine) in males at post-emergence days 0-16. The development of locomotor and flight activities were recorded over the same period. Hemolymph levels of dopamine and N-acetyldopamine were found to increase at the time of onset of mating flight activity and those of dopamine decreased thereafter. Both locomotor and flight activities increased in parallel with hemolymph dopamine levels but the increased activity levels were maintained following decline of dopamine levels. Brain and meso-metathoracic ganglia levels of dopamine showed a similar developmental profile to hemolymph dopamine levels. Locomotor activities were temporarily inhibited by injection of a dopamine receptor antagonist (cis(Z)-flupenthixol) into the thorax, and were enhanced by injection of a dopamine-receptor agonist (6,7-ADTN). These results suggest that dopamine regulates locomotor activities for mating and plays a role downstream of JH in premature males in honeybees. PMID- 20303975 TI - Dopamine down-regulates activity of alkaline phosphatase in Drosophila: the role of D2-like receptors. AB - The effect of a rise in dopamine (DA) level as a result of a mutation, stress or pharmacological treatment on the activity of the enzyme of its synthesis, alkaline phosphatase (ALP) in females of Drosophila virilis and Drosophila melanogaster has been studied. It has been found that regardless of its nature, a rise in DA level has a negative effect on ALP activity, which indicates that DA down-regulates activity of the enzyme. The effects of bromocriptine (an agonist of Drosophila dopamine 2-like receptor (DD2R)) on ALP activity have been studied. ALP activity was found to drop in response to bromocriptine in flies. Conversely ALP activity was increased in flies with reduced DD2R expression (i.e. Actin5C Gal4>UAS-ds-DD2R RNA-interference flies) vs. corresponding controls (i.e. Actin5C Gal4>w1118 flies). Bromocriptine treatment of RNAi flies rescues ALP activity to the level typical of Actin5C-Gal4>w1118 flies. A change in DD2R number or availability was found not to prevent the response of ALP to heat stress, but to change the intensity of its response to the stress exposure. The role of D2-like receptors in down-regulation of ALP activity by DA and in ALP response to stressor in Drosophila is discussed. PMID- 20303977 TI - The effects of phosphomimetic lid mutation on the thermostability of the N terminal domain of MDM2. AB - The multidomain E3 ubiquitin ligase MDM2 catalyzes p53 ubiquitination by a "dual site" docking mechanism whereby MDM2 binding to at least two distinct peptide motifs on p53 promotes ubiquitination. One protein-protein interaction occurs between the N-terminal hydrophobic pocket of MDM2 and the transactivation motif of p53, and the second interaction occurs between the acidic domain of MDM2 and a motif in the DNA-binding domain of p53. A flexible N-terminal pseudo-substrate or "lid" adjacent to the N-terminal hydrophobic pocket of MDM2 has a phosphorylation site, and there are distinct models proposed on how the phosphorylated lid could affect MDM2 function. Biochemical studies have predicted that phosphomimetic mutation will stabilize the lid on the surface of MDM2 and will "open" the hydrophobic pocket and stabilize the MDM2-p53 complex, while NMR studies proposed that phosphomimetic mutation "closes" the lid over the MDM2 pocket and inhibits MDM2-p53 complex formation. To resolve these discrepancies, we utilized a quantitative fluorescence-based dye binding assay to measure the thermal unfolding of wild-type (wt), DeltaLid, and S17D N-terminal domains of MDM2 as a function of increasing ligand concentration. Our data reveal that S17D lid mutation increases, rather than decreases, the thermostability of the N-terminal domain of MDM2 in the absence or in the presence of ligand. DeltaLid mutation, by contrast, increases MDM2 thermoinstability. This is consistent with biochemical data, using full-length MDM2, showing that the S17D mutation stabilizes the MDM2 p53 complex and increases the specific activity of the E3 ubiquitin ligase function of MDM2. These data indicate that phosphomimetic lid mutation results in an "opening," rather than a "closing," of the pocket of MDM2 and highlight the ability of small intrinsically disordered or unstructured peptide motifs to regulate the specific activity of a protein. PMID- 20303976 TI - Reduced vascular responsiveness to adiponectin in hyperlipidemic rats--mechanisms and significance. AB - Deficiency of adiponectin (APN), an adipocyte-derived vascular protective molecule, contributes to diabetic vascular injury. The current study determined whether obesity/hyperlipidemia may alter the vascular response to APN, and investigated the involved mechanisms and pathologic significance. Adult male Sprague-Dawley rats were fed a regular or high-fat diet (HF) for 4-16 weeks. Circulating APN levels, aortic pAMPK/AMPK, peNOS/eNOS, and APN receptor expression levels were determined. Compared to time-matched animals fed control diet, plasma APN levels in HF-diet animals were significantly increased at 8 weeks, and rapidly declined thereafter. Despite unchanged or elevated circulating APN levels, phosphorylated AMPK and eNOS in vascular tissue were significantly reduced at all observed time points. Recombinant full-length APN (rAPN)-induced AMPK/eNOS phosphorylation and vasodilatation were significantly reduced in 16 week obese/hyperlipidemic aortic segments. Vascular APN receptor 1 (AdipoR1) and receptor 2 (AdipoR2) expression were significantly reduced 16 weeks after HF diet. Pre-incubation of rAPN with obese/hyperlipidemic plasma, but not with normal plasma, significantly reduced its AMPK and eNOS activation effect, and blunted its protective effect against TNFalpha-induced HUVEC apoptosis. This study demonstrated for the first time that obesity/hyperlipidemia reduces vascular responsiveness to APN. Modification/inactivation of APN by unidentified factors present in obese/hyperlipidemic plasma, decreased vascular AdipoR1/R2 expression, and reduced circulating APN levels contribute to reduced vascular responsiveness to APN at different stages of the obese condition. Reduced APN bioactivity allows unmitigated TNFalpha pro-apoptotic and pro-inflammatory actions, contributing to vascular injury in obesity/hyperlipidemia. PMID- 20303978 TI - Structure and conformational dynamics of the metalloregulator MerR upon binding of Hg(II). AB - The bacterial metalloregulator MerR is the index case of an eponymous family of regulatory proteins, which controls the transcription of a set of genes (the mer operon) conferring mercury resistance in many bacteria. Homodimeric MerR represses transcription in the absence of mercury and activates transcription upon Hg(II) binding. Here, the average structures of the apo and Hg(II)-bound forms of MerR in aqueous solution are examined using small-angle X-ray scattering, indicating an extended conformation of the metal-bound protein and revealing the existence of a novel compact conformation in the absence of Hg(II). Molecular dynamics (MD) simulations are performed to characterize the conformational dynamics of the Hg(II)-bound form. In both small-angle X-ray scattering and MD, the average torsional angle between DNA-binding domains is approximately 65 degrees. Furthermore, in MD, interdomain motions on a timescale of approximately 10 ns involving large-amplitude (approximately 20 A) domain opening-and-closing, coupled to approximately 40 degrees variations of interdomain torsional angle, are revealed. This correlated domain motion may propagate allosteric changes from the metal-binding site to the DNA-binding site while maintaining DNA contacts required to initiate DNA underwinding. PMID- 20303979 TI - Crystal structure of sulfide:quinone oxidoreductase from Acidithiobacillus ferrooxidans: insights into sulfidotrophic respiration and detoxification. AB - Sulfide:quinone oxidoreductase from the acidophilic and chemolithotrophic bacterium Acidithiobacillus ferrooxidans was expressed in Escherichia coli and crystallized, and its X-ray molecular structure was determined to 2.3 A resolution for native unbound protein in space group P4(2)2(1)2 . The decylubiquinone-bound structure and the Cys160Ala variant structure were subsequently determined to 2.3 A and 2.05 A resolutions, respectively, in space group P6(2)22 . The enzymatic reaction catalyzed by sulfide:quinone oxidoreductase includes the oxidation of sulfide compounds H(2)S, HS(-), and S(2 ) to soluble polysulfide chains or to elemental sulfur in the form of octasulfur rings; these oxidations are coupled to the reduction of ubiquinone or menaquinone. The enzyme comprises two tandem Rossmann fold domains and a flexible C-terminal domain encompassing two amphipathic helices that are thought to provide for membrane anchoring. The second amphipathic helix unwinds and changes its orientation in the hexagonal crystal form. The protein forms a dimer that could be inserted into the membrane to a depth of approximately 20 A. It has an endogenous flavin adenine dinucleotide (FAD) cofactor that is noncovalently bound in the N-terminal domain. Several wide channels connect the FAD cofactor to the exterior of the protein molecule; some of the channels would provide access to the membrane. The ubiquinone molecule is bound in one of these channels; its benzoquinone ring is stacked between the aromatic rings of two conserved Phe residues, and it closely approaches the isoalloxazine moiety of the FAD cofactor. Two active-site cysteine residues situated on the re side of the FAD cofactor form a branched polysulfide bridge. Cys356 disulfide acts as a nucleophile that attacks the C4A atom of the FAD cofactor in electron transfer reaction. The third essential cysteine Cys128 is not modified in these structures; its role is likely confined to the release of the polysulfur product. PMID- 20303980 TI - Structure of the minimal interface between ApoE and LRP. AB - Clusters of complement-type ligand-binding repeats (CRs) in the low-density lipoprotein receptor (LDLR) family are thought to mediate the interactions with their various ligands. Apolipoprotein E (ApoE), a key ligand for cholesterol homeostasis, has been shown to interact with LDLR-related protein 1 (LRP) through these clusters. The segment comprising the receptor-binding portion of ApoE (residues 130-149) has been found to have a weak affinity for isolated CRs. We have fused this region of ApoE to a high-affinity CR from LRP (CR17) for structural elucidation of the complex. The interface reveals a motif that has previously been observed in CR domains with other binding partners, but with several novel features. Comparison to free CR17 reveals that very few structural changes result from this binding event, but significant changes in intrinsic dynamics are observed upon binding. NMR perturbation experiments suggest that this interface may be similar to several other ligand interactions with LDLRs. PMID- 20303981 TI - Crystal structures of the CBS and DRTGG domains of the regulatory region of Clostridiumperfringens pyrophosphatase complexed with the inhibitor, AMP, and activator, diadenosine tetraphosphate. AB - Nucleotide-binding cystathionine beta-synthase (CBS) domains serve as regulatory units in numerous proteins distributed in all kingdoms of life. However, the underlying regulatory mechanisms remain to be established. Recently, we described a subfamily of CBS domain-containing pyrophosphatases (PPases) within family II PPases. Here, we express a novel CBS-PPase from Clostridium perfringens (CPE2055) and show that the enzyme is inhibited by AMP and activated by a novel effector, diadenosine 5',5-P1,P4-tetraphosphate (AP(4)A). The structures of the AMP and AP(4)A complexes of the regulatory region of C. perfringens PPase (cpCBS), comprising a pair of CBS domains interlinked by a DRTGG domain, were determined at 2.3 A resolution using X-ray crystallography. The structures obtained are the first structures of a DRTGG domain as part of a larger protein structure. The AMP complex contains two AMP molecules per cpCBS dimer, each bound to a single monomer, whereas in the activator-bound complex, one AP(4)A molecule bridges two monomers. In the nucleotide-bound structures, activator binding induces significant opening of the CBS domain interface, compared with the inhibitor complex. These results provide structural insight into the mechanism of CBS-PPase regulation by nucleotides. PMID- 20303983 TI - Negative feedback of extracellular ADP on ATP release in goldfish hepatocytes: a theoretical study. AB - A mathematical model was built to account for the kinetic of extracellular ATP (ATPe) and extracellular ADP (ADPe) concentrations from goldfish hepatocytes exposed to hypotonicity. The model was based on previous experimental results on the time course of ATPe accumulation, ectoATPase activity, and cell viability [Pafundo et al., 2008]. The kinetic of ATPe is controlled by a lytic ATP flux, a non-lytic ATP flux, and ecto-ATPase activity, whereas ADPe kinetic is governed by a lytic ADP flux and both ecto-ATPase and ecto-ADPase activities. Non-lytic ATPe efflux was included as a diffusion equation modulated by ATPe activation (positive feedback) and ADPe inhibition (negative feedback). The model yielded physically meaningful and stable steady-state solutions, was able to fit the experimental time evolution of ATPe and simulated the concomitant kinetic of ADPe. According to the model during the first minute of hypotonicity the concentration of ATPe is mainly governed by both lytic and non-lytic ATP efflux, with almost no contribution from ecto-ATPase activity. Later on, ecto-ATPase activity becomes important in defining the time dependent decay of ATPe levels. ADPe inhibition of the non-lytic ATP efflux was strong, whereas ATPe activation was minimal. Finally, the model was able to predict the consequences of partial inhibition of ecto-ATPase activity on the ATPe kinetic, thus emulating the exposure of goldfish cells to hypotonic medium in the presence of the ATP analog AMP-PCP. The model predicts this analog to both inhibit ectoATPase activity and increase non-lytic ATP release. PMID- 20303984 TI - A mathematical model for cell size control in fission yeast. AB - Experimental investigations of cell size control in fission yeast Schizosaccharomyces pombe have illustrated that the cell cycle features 'sizer' and 'timer' phases which are distinguished by a growth rate changing point. Based on current biological knowledge of fission yeast size control, we propose here a model of ordinary differential equations (ODEs) for a possible explanation of the facts and control mechanism which is coupled with the cell cycle. Simulation results of the ODE model are demonstrated to agree with experimental data for the wild type and the cdc2-33 mutant. We show that the coupling of cell growth to cell division by translational control may account for observed properties of size control in fission yeast. As the translational control in the expression of cycle proteins Cdc13 and Cdc25 constructs positive feedback loops, the dynamical activities of the key components undergoes a rapid rising after a preliminary stage of slow increase. The coupling of this dynamical behavior to the elongation of the cell naturally gives rise to a rate change point and to 'sizer' and 'timer' phases, which characterize the cell cycle of fission yeast. PMID- 20303985 TI - Higher order Boolean networks as models of cell state dynamics. AB - The regulation of the cell state is a complex process involving several components. These complex dynamics can be modeled using Boolean networks, allowing us to explain the existence of different cell states and the transition between them. Boolean models have been introduced both as specific examples and as ensemble or distribution network models. However, current ensemble Boolean network models do not make a systematic distinction between different cell components such as epigenetic factors, gene and transcription factors. Consequently, we still do not understand their relative contributions in controlling the cell fate. In this work we introduce and study higher order Boolean networks, which feature an explicit distinction between the different cell components and the types of interactions between them. We show that the stability of the cell state dynamics can be determined solving the eigenvalue problem of a matrix representing the regulatory interactions and their strengths. The qualitative analysis of this problem indicates that, in addition to the classification into stable and chaotic regimes, the cell state can be simple or complex depending on whether it can be deduced from the independent study of its components or not. Finally, we illustrate how the model can be expanded considering higher levels and higher order dynamics. PMID- 20303982 TI - Three-dimensional multispecies nonlinear tumor growth-II: Tumor invasion and angiogenesis. AB - We extend the diffuse interface model developed in Wise et al. (2008) to study nonlinear tumor growth in 3-D. Extensions include the tracking of multiple viable cell species populations through a continuum diffuse-interface method, onset and aging of discrete tumor vessels through angiogenesis, and incorporation of individual cell movement using a hybrid continuum-discrete approach. We investigate disease progression as a function of cellular-scale parameters such as proliferation and oxygen/nutrient uptake rates. We find that heterogeneity in the physiologically complex tumor microenvironment, caused by non-uniform distribution of oxygen, cell nutrients, and metabolites, as well as phenotypic changes affecting cellular-scale parameters, can be quantitatively linked to the tumor macro-scale as a mechanism that promotes morphological instability. This instability leads to invasion through tumor infiltration of surrounding healthy tissue. Models that employ a biologically founded, multiscale approach, as illustrated in this work, could help to quantitatively link the critical effect of heterogeneity in the tumor microenvironment with clinically observed tumor growth and invasion. Using patient tumor-specific parameter values, this may provide a predictive tool to characterize the complex in vivo tumor physiological characteristics and clinical response, and thus lead to improved treatment modalities and prognosis. PMID- 20303986 TI - A model for cyst lumen expansion and size regulation via fluid secretion. AB - Many internal epithelial organs derive from cysts, which are tissues comprised of bent epithelial cell layers enclosing a lumen. Ion accumulation in the lumen drives water influx and consequently water accumulation and cyst expansion. Lumen size recognition is important for the regulation of organ size. When lumen size and cyst size are not controlled, diseases can result; for instance, renal failure of the kidney. We develop a mechanistic mathematical model of lumen expansion in order to investigate the mechanisms for saturation of cyst growth. We include fluid accumulation in the lumen, osmotic and elastic pressure, ion transport and stretch-induced cell division. We find that the lumen volume increases in two phases: first, due to fluid accumulation stretching the cells, then in the second phase, the volume increase follows the increase in cell number until proliferation ceases as stretch forces relax. The model is quantitatively fitted to published data of in vitro cyst growth and predicts steady state lumen size as a function of the model parameters. PMID- 20303987 TI - Scaling behaviors of weighted food webs as energy transportation networks. AB - Food webs can be regarded as energy transporting networks in which the weight of each edge denotes the energy flux between two species. By investigating 21 empirical weighted food webs as energy flow networks, we found several ubiquitous scaling behaviors. Two random variables A(i) and C(i) defined for each vertex i, representing the total flux (also called vertex intensity) and total indirect effect or energy store of i, were found to follow power law distributions with the exponents alpha approximately 1.32 and beta approximately 1.33, respectively. Another scaling behavior is the power law relationship, C(i) approximately A(i)(eta), where eta approximately 1.02. This is known as the allometric scaling power law relationship because A(i) can be treated as metabolism and C(i) as the body mass of the sub-network rooted from the vertex i, according to the algorithm presented in this paper. Finally, a simple relationship among these power law exponents, eta=(alpha-1)/(beta-1), was mathematically derived and tested by the empirical food webs. PMID- 20303988 TI - The Arabidopsis thaliana flower organ specification gene regulatory network determines a robust differentiation process. AB - The Arabidopsis thaliana flower organ specification gene regulatory network (FOS GRN) has been modeled previously as a discrete dynamical system, recovering as steady states configurations that match the genetic profiles described in primordial cells of inflorescence, sepals, petals, stamens and carpels during early flower development. In this study, we first update the FOS-GRN by adding interactions and modifying some rules according to new experimental data. A discrete model of this updated version of the network has a dynamical behavior identical to previous versions, under both wild type and mutant conditions, thus confirming its robustness. Then, we develop a continuous version of the FOS-GRN using a new methodology that builds upon previous proposals. The fixed point attractors of the discrete system are all observed in the continuous model, but the latter also contains new steady states that might correspond to genetic activation states present briefly during the early phases of flower development. We show that both the discrete and the continuous models recover the observed stable gene configurations observed in the inflorescence meristem, as well as the primordial cells of sepals, petals, stamens and carpels. Additionally, both models are subjected to perturbations in order to establish the nature of additional signals that may suffice to determine the experimentally observed order of appearance of floral organs. Our results thus describe a possible mechanism by which the network canalizes molecular signals and/or noise, thus conferring robustness to the differentiation process. PMID- 20303989 TI - KMUP-1 ameliorates monocrotaline-induced pulmonary arterial hypertension through the modulation of Ca2+ sensitization and K+-channel. AB - AIMS: This study investigates the actions of KMUP-1 on RhoA/Rho-kinase (ROCK) dependent Ca(2+) sensitization and the K(+)-channel in chronic pulmonary arterial hypertension (PAH) rats. MAIN METHODS: Sprague-Dawley rats were divided into control, monocrotaline (MCT), and MCT+KMUP-1 groups. PAH was induced by a single intraperitoneal injection (i.p.) of MCT (60 mg/kg). KMUP-1 (5 mg/kg, i.p.) was administered once daily for 21 days to prevent MCT-induced PAH. All rats were sacrificed on day 22. KEY FINDINGS: MCT-induced increased right ventricular systolic pressure (RVSP) and right ventricular hypertrophy were prevented by KMUP 1. In myograph experiments, KCl (80 mM), phenylephrine (10 microM) and K(+) channel inhibitors (TEA, 10 mM; paxilline, 10 microM; 4-AP, 5 mM) induced weak PA contractions in MCT-treated rats compared to controls, but the PA reactivity was restored in MCT+KMUP-1-treated rats. By contrast, in beta-escin- or alpha-toxin permeabilized PAs, CaCl(2)-induced (1.25 mM, pCa 5.1) contractions were stronger in MCT-treated rats, and this action was suppressed in MCT+KMUP-1-treated rats. PA relaxation in response to the ROCK inhibitor Y27632 (0.1 microM) was much higher in MCT-treated rats than in control rats. In Western blot analysis, the expression of Ca(2+)-activated K(+) (BK(Ca)) and voltage-gated K(+) channels (Kv2.1 and Kv1.5), and ROCK II proteins was elevated in MCT-treated rats and suppressed in MCT+KMUP-1-treated rats. We suggest that MCT-treated rats upregulate K(+)-channel proteins to adapt to chronic PAH. SIGNIFICANCE: KMUP-1 protects against PAH and restores PA vessel tone in MCT-treated rats, attributed to alteration of Ca(2+) sensitivity and K(+)-channel function. PMID- 20303990 TI - Evaluating treatment of hepatitis C for hemolytic anemia management. AB - The combination therapy of antiviral peg-interferon and ribavirin has evolved as one of the better treatments for hepatitis C. In spite of its success in controlling hepatitis C infection, it has also been associated with treatment related adverse side effects. The most common and life threatening among them is hemolytic anemia, necessitating dose reduction or therapy cessation. The presence of this side effect leads to a trade-off between continuing the treatment and exacerbating the side effects versus decreasing dosage to relieve severe side effects while allowing the disease to progress. The drug epoietin (epoetin) is often administered to stimulate the production of red blood cells (RBC) in the bone marrow, in order to allow treatment without anemia. This paper uses mathematical models to study the effect of combination therapy in light of anemia. In order to achieve this we introduce RBC concentration and amount of drug in the body as state variables in the usual immunological virus infection model. Analysis of this model provides a quantification of the amount of drug a body can tolerate without succumbing to hemolytic anemia. Indirect estimation of parameters allow us to calculate the necessary increment in RBC production to be > or =2.3 times the patient's original RBC production rate to sustain the entire course of treatment without encountering anemia in a sensitive patient. PMID- 20303991 TI - Exploring voltage-dependent ion channels in silico by hysteretic conductance. AB - Kinetic models of voltage-dependent ion channels are normally inferred from time records of macroscopic current relaxation or microscopic single channel data. A complementary explorative approach is outlined. Hysteretic conductance refers to conductance delays in response to voltage changes, delays at either macroscopic or microscopic levels of observation. It enables complementary assessments of model assumptions and gating schemes of voltage-dependent channels, e.g. independent versus cooperative gating, and multiple gating modes. Under the Hodgkin-Huxley condition of independent gating, and under ideal measurement conditions, hysteretic conductance makes it also possible to estimate voltage dependent rate functions. The argument is mainly theoretical, based on experimental observations, and illustrated by simulations of Markov kinetic models. PMID- 20303992 TI - Theoretical modeling of fluid flow in cellular biological media: an overview. AB - Fluid-structure interactions strongly affect, in multiple ways, the structure and function of cellular biological media, such as tissues, biofilms, and cell entrapping gels. Mathematical models and computer simulation are important tools in advancing our understanding of these interactions, interpreting experimental observations, and designing novel processes and biomaterials. In this paper, we present a comprehensive survey and highlight promising directions of future research on theoretical modeling of momentum transport in cellular biological media with focus on the formulation of governing equations and the calculation of material properties both theoretically and experimentally. With regard to the governing equations, significant work has been done with single-scale approaches (e.g. mixture theory), whereas traditional upscaling methods (e.g. homogenization, volume averaging) or multiscale equation-free approaches have received limited attention. The underlying concepts, strengths, and limitations of each approach, as well as examples of use in the field of biomaterials are presented. The current status of knowledge regarding the dependence of macroscopic material properties on the volume fractions, geometry, and intrinsic material properties of the constituent phases (cells, extracellular matrix and fluid) is also presented. The observation of conformational changes that occur at finer levels of the structural hierarchy during momentum transport, the correlation of macro-properties with geometrical and topological features of materials with heterogeneous and anisotropic microstructure, as well as the determination of dynamic material properties are among important challenges for future research. PMID- 20303993 TI - The dynamic behavior of chemically "stiffened" red blood cells in microchannel flows. AB - The rigidity of red blood cells (RBCs) plays an important role in whole blood viscosity and is correlated with several cardiovascular diseases. Two chemical agents that are commonly used to study cell deformation are diamide and glutaraldehyde. Despite diamide's common usage, there are discrepancies in the literature surrounding diamide's effect on the deformation of RBCs in shear and pressure-driven flows; in particular, shear flow experiments have shown that diamide stiffens cells, while pressure-driven flow in capillaries did not give this result. We performed pressure-driven flow experiments with RBCs in a microfluidic constriction and quantified the cell dynamics using high-speed imaging. Diamide, which affects RBCs by cross-linking spectrin skeletal membrane proteins, did not reduce deformation and showed an unchanged effective strain rate when compared to healthy cells. In contrast, glutaraldehyde, which is a non specific fixative that acts on all components of the cell, did reduce deformation and showed increased instances of tumbling, both of which are characteristic features of stiffened, or rigidified, cells. Because glutaraldehyde increases the effective viscosity of the cytoplasm and lipid membrane while diamide does not, one possible explanation for our results is that viscous effects in the cytoplasm and/or lipid membrane are a dominant factor in dictating dynamic responses of RBCs in pressure-driven flows. Finally, literature on the use of diamide as a stiffening agent is summarized, and provides supporting evidence for our conclusions. PMID- 20303994 TI - Impaired digital vascular function mimicking Raynaud's phenomenon as a complication of argon laser therapy in tuberous sclerosis. PMID- 20303995 TI - Three-dimensional analysis of tumour vascular corrosion casts using stereoimaging and micro-computed tomography. AB - OBJECTIVE: In order to perform effective translational research for cancer therapy, we need to employ pre-clinical models which reflect the clinical situation. The purpose of this study was to quantitatively compare the vascular architecture of human colorectal cancer and experimental tumour models to determine the suitability of animal models for vascular studies and antivascular therapy. METHODS: In this study we investigated the three-dimensional properties of colonic tumour vasculature in both human clinical tissues (normal mucosa control [n=20], carcinoma [n=20] and adenoma [n=6]) and murine colorectal xenografts (LS147T [n=6] and SW1222 [n=6]). Scanning Electron Microscope Stereoimaging (SEM) and X-ray Micro-Computed Tomography (Micro-CT) methods were employed for 3D analyses of the vascular corrosion casts from these tissues. RESULTS: Morphological measurements showed that there were significant differences in the underlying morphology in the different tissues. Of the studied xenografts, LS147T is more consistently similar to the vascular architecture of the human carcinoma than SW1222. The only reversal of this is for the inter vessel distance. CONCLUSION: While SEM stereoimaging provided better surface detailed resolution of the corrosion casts, it was complimented by the fully 3D micro-CT method. Comparison made between the xenografts and clinical tumours showed that the LS147T xenografts shared many similarities with the clinical tumour vasculature. This study provides insight into how to select the most suitable pre-clinical models for translational studies of clinical cancer therapy. PMID- 20303996 TI - Pharmacological magnetic resonance imaging of muscarinic acetylcholine receptor activation in rat brain. AB - The central cholinergic system is involved in several cognitive functions such as attention, consciousness, learning and memory. Functional imaging of this neurotransmitter system may provide novel opportunities in the diagnosis and evaluation of cognitive disorders. The aim of this study was to investigate the spatial and temporal activation patterns of muscarinic acetylcholine receptor (mAChR) stimulation in rat brain with pharmacological magnetic resonance imaging (phMRI). We performed blood oxygenation level-dependent (BOLD) MRI and contrast enhanced cerebral blood volume (CBV)-weighted MRI combined with injection of pilocarpine, a non-selective mAChR agonist. BOLD and CBV responses were assessed after pretreatment with methyl-scopolamine in order to block peripheral muscarinic effects. Region-of-interest analysis in individual animals and group level independent component analysis failed to show significant BOLD signal changes following pilocarpine injection. However, with contrast-enhanced CBV weighted MRI, positive CBV responses were detected in the cerebral cortex, thalamus, and hippocampus whereas a negative CBV response was observed in the striatum. Thus, pilocarpine-induced significant activation responses in brain regions that are known to have a high density of muscarinic receptors. Our study demonstrates that phMRI of mAChR stimulation in rats allows functional assessment of the cholinergic system in vivo. PMID- 20303998 TI - Executive impairment in Parkinson's disease: response automaticity and task switching. AB - Patients with Parkinson's disease (PD) show slowed movement initiation and can have deficits in executive function, leading to impairments in controlling involuntary behavior. This results in difficulties performing an antisaccade, which requires one to suppress an automatic eye movement (a prosaccade) to a visual stimulus, and execute a voluntary eye movement in the opposite direction. Antisaccade deficits are similar to those seen in task switching, whereby one is required to change a response after performing a different behavior. Both antisaccade (Hood et al., 2007) and task switching (Cools, Barker, Sahakian, & Robbins, 2001) deficits in PD have been attributed to fronto-basal ganglia (BG) dysfunction. Previously, we demonstrated with functional magnetic resonance imaging that BG circuitry is important to both task switching and voluntary saccade generation, as greater caudate activation was seen when healthy young adults first prepared a prosaccade, but then switched to an antisaccade (Cameron, Coe, et al., 2009). Therefore, we hypothesized that PD patients would have difficulty switching from one saccade response to the other, with particular impairment in switching from a pro to an antisaccade. Here, we not only confirmed this prediction, but also showed that PD patients performed better than controls in switching from an anti to a prosaccade. This suggests that task switching deficits in PD are particularly pronounced when more automatic behavior needs to be overridden with alternative behavior. We suggest that this occurs primarily at the level of establishing the appropriate task set, which is an internalized rule that governs how to respond. PMID- 20303997 TI - Genistein directly inhibits native and recombinant NMDA receptors. AB - The protein tyrosine kinase (PTK) inhibitor genistein has been widely used to examine potential effects of tyrosine phosphorylation on neurotransmitter function. We report here that genistein inhibits N-methyl-d-aspartate (NMDA) receptors through a direct effect. Whole-cell NMDA-activated current was recorded in native receptors from mouse hippocampal slice culture and rat recombinant NR1aNR2A and NR1aNR2B receptors transiently expressed in HEK293 cells. Extracellular application of genistein and NMDA reversibly inhibited NMDA activated current. The inhibition of NMDA-activated current by genistein applied externally was not affected when genistein was also pre-equilibrated in the intracellular solution. Daidzein, an analog of genistein that does not block PTK, also inhibited NMDA-activated current. Coapplication of lavendustin A, a specific inhibitor of PTK, had no effect on the NMDA response. Moreover, genistein-induced inhibition of NMDA-activated current displayed concentration- and voltage dependence. Our results demonstrate that genistein has a direct inhibitory effect on NMDA receptors that is not mediated via inhibition of tyrosine kinase. Thus, other PTK inhibitors may be more suitable for studying involvement of PTKs in NMDA receptor-mediated events. PMID- 20303999 TI - The development of satiation in bulimia nervosa. AB - Bulimia nervosa (BN) is characterized by the recurrent consumption of excessive amounts of food (binge eating) followed by inappropriate compensatory behaviors. A leading hypothesis is that the persistence of BN may be due, in part, to a disturbance in the development of satiation. Because patients with BN consume larger meals than controls, previous studies have not been able to directly compare the development of satiation. In order to address this problem, subjects consumed large meals of predetermined size without knowing when they would be stopped. Twenty-one women with BN and 13 control women participated in a study in which they rated hunger and fullness during the course of a 975 g liquid meal eaten from an opaque reservoir. Subjects' ratings were obtained after each 75 g increment of consumption. There were no statistically significant differences between the two groups in the mean ratings of hunger or of fullness before, after, or during the meal. Individuals with BN consumed the meal more rapidly than control participants. These results suggest that, when individuals with BN are not instructed to binge eat and do not control meal size, they do not manifest a disturbance in reported satiation over the course of a large liquid meal. PMID- 20304000 TI - Modeling toxoplasmosis spread in cat populations under vaccination. AB - In this paper we present an epidemiological model to study the transmission dynamics of toxoplasmosis in a cat population under a continuous vaccination schedule. We explore the dynamics of toxoplasmosis at the population level using a mathematical model that includes the effect of oocyst, since the probability of acquisition of Toxoplasma Gondii infection depends on the environmental load of the parasite. This model considers indirectly the infection of prey through the oocyst shedding by cats. We prove that the basic reproduction number R(0) is a threshold value that completely determines the global dynamics and the outcome of the disease. Numerical computer simulations are presented to investigate different scenarios. These simulations show the effectiveness of a constant vaccination program. PMID- 20304001 TI - Morphological differences between the eyeballs of nocturnal and diurnal amniotes revisited from optical perspectives of visual environments. AB - Eyes are expected to be adapted to the physical characteristics of the visual environment, yet previous analyses failed to corroborate this observation. We demonstrate that nocturnal, crepuscular/cathemeral, and diurnal activity patterns occupy distinct areas in morphospace and are identified with high accuracies based on a discriminant analysis of visual performance features. Not only nocturnal and diurnal diel activity patterns are reflected in macroscopic morphology of the eyeball, but also the crepuscular/cathemeral patterns. The eyeball morphology of the latter was believed to be undistinguishable between diurnal and nocturnal types. We show that all three categories can be delineated with high accuracies. PMID- 20304002 TI - The detection of moving objects by moving observers. AB - When an observer moves through the world, he or she must detect moving objects in order to avoid or intercept them. Accomplishing this task presents a problem for the visual system, because the motion of the observer causes the images of nearly all objects in the scene to move across the retina. We tested observers' abilities to detect a moving object when its angle of motion deviated from the radial optic flow pattern generated by observer motion in a straight line. To test whether global information is important for this task, we compared the results for a radial pattern with those for a deformation pattern. The results show that observer accuracy depends on the global pattern of the optic flow. In addition, we tested the effects of the duration of the trial, the number of objects, the eccentricity of the moving object and the speed of the observer. PMID- 20304003 TI - Changes in dynamics of accommodation after accommodative facility training in myopes and emmetropes. AB - This study evaluates the effect of accommodative facility training in myopes and emmetropes. Monocular accommodative facility was measured in nine myopes and nine emmetropes for distance and near. Subjective facility was recorded with automated flippers and objective measurements were simultaneously taken with a PowerRefractor. Accommodative facility training (a sequence of 5 min monocular right eye, 5 min monocular left eye, 5 min binocular) was given on three consecutive days and facility was re-assessed on the fifth day. The results showed that training improved the facility rate in both groups. The improvement in facility rates were linked to the time constants and peak velocity of accommodation. Some changes in amplitude seen in emmetropes indicate an improvement in facility rate at the expense of an accurate accommodation response. PMID- 20304004 TI - A novel functional rabbit IL-7 isoform. AB - IL-7 is required for B cell development in mouse and is a key regulator of T cell development and peripheral T cell homeostasis in mouse and human. Recently, we found that IL-7 is expressed in rabbit bone marrow and in vitro, is required for differentiation of lymphoid progenitors to B and T lineage cells. Herein, we report the identification of a novel rabbit IL-7 isoform, IL-7II. Recombinant IL 7II (rIL-7II) binds lymphocytes via the IL-7R and induces phosphorylation of STAT5. Further, rIL-7II supports proliferation and differentiation of BM progenitor cells into B and T lineage cells. IL7-II is generated by alternative splicing, with an 11 amino acid insertion encoded by a separate exon, exon 2b. Exon 2b is conserved in other lagomorphs, in Perissodactyla, Artiodactyla, and Carnivora, but is absent in mouse and human. PMID- 20304006 TI - Expression and purification of ataxin-1 protein. AB - Ataxin-1 is part of a larger family of polyglutamine-containing proteins that is linked to nine distinct neurodegenerative disorders. There are no known effective therapies for any of these expanded polyglutamine tract disorders. One possible reason for this is the lack of sufficient amounts of pure polyglutamine containing proteins suitable for biochemical and conformational studies. Here, we show that we were able to successfully purify a non-pathological, wild-type human ataxin-1 protein containing a 30-glutamine repeat sequence. This ataxin-1 protein was expressed in Escherichia coli as a fusion protein with a GST tag at the N terminus and a double (His)(6) tag at the C-terminus. The devised dual affinity tag strategy allowed successful purification of the full-length ataxin-1 fusion protein to 90% homogeneity as confirmed by Western blot analysis using the two monoclonal ataxin-1 antibodies developed in our laboratory. In addition, the GST tag was successfully removed from the purified ataxin-1 fusion protein by treatment with Tobacco etch virus (TEV) protease. Since polyglutamine-containing proteins tend to aggregate, solvents/buffers that minimize aggregation have been used in the purification process. This dual affinity purification protocol could serve as a useful basis for purifying aggregation-prone proteins that are involved in other neurodegenerative diseases. PMID- 20304007 TI - Using a rate-frequency curve method to assess the rewarding properties of morphine in the intracranial self-stimulation paradigm in rats. AB - Intracranial self-stimulation (ICSS) is a sophisticated paradigm that can be used to assess the rewarding properties of drugs of abuse such as cocaine and amphetamine. Initial studies using this method to assess brain stimulation reward (BSR) examined the enhancement of response rates after drug administration. In the mid to late 1980s several groups began implementing paradigms to assess the direct rewarding effects of drugs of abuse that, for the most part, are independent of rate (i.e., progressive-ratio, auto-titration, rate-frequency curve), providing a representative assessment of a drugs rewarding effects. However, some drugs such as morphine and ethanol, which are known to have abuse potential, have sedative effects that may impede the ability to accurately quantify rewarding effects, even in these rate-independent paradigms. Few studies to date report effects of morphine in the ICSS paradigm and those that do appear to be inconsistent, lack robustness, have not been reproducible by other groups, or require inconvenient experimental designs. Here, we demonstrate a reliable and robust method to assess the rewarding effects of morphine using the rate frequency curve paradigm. PMID- 20304005 TI - Granger causality relationships between local field potentials in an animal model of temporal lobe epilepsy. AB - An understanding of the in vivo spatial emergence of abnormal brain activity during spontaneous seizure onset is critical to future early seizure detection and closed-loop seizure prevention therapies. In this study, we use Granger causality (GC) to determine the strength and direction of relationships between local field potentials (LFPs) recorded from bilateral microelectrode arrays in an intermittent spontaneous seizure model of chronic temporal lobe epilepsy before, during, and after Racine grade partial onset generalized seizures. Our results indicate distinct patterns of directional GC relationships within the hippocampus, specifically from the CA1 subfield to the dentate gyrus, prior to and during seizure onset. Our results suggest sequential and hierarchical temporal relationships between the CA1 and dentate gyrus within and across hippocampal hemispheres during seizure. Additionally, our analysis suggests a reversal in the direction of GC relationships during seizure, from an abnormal pattern to more anatomically expected pattern. This reversal correlates well with the observed behavioral transition from tonic to clonic seizure in time-locked video. These findings highlight the utility of GC to reveal dynamic directional temporal relationships between multichannel LFP recordings from multiple brain regions during unprovoked spontaneous seizures. PMID- 20304008 TI - Intrinsic optical imaging of directional selectivity in rat barrel cortex: application of a multidirectional magnetic whisker stimulator. AB - Using intrinsic optical imaging methods, somatosensory-evoked neural activity was visualized in the rat barrel cortex at high spatial resolution in order to obtain cortical maps of the directional selectivity of whisker deflection. For this task, a special multidirectional mechanical stimulator was developed in our laboratory. The vibrissae were covered with magnetic paint and deflection was performed using a custom-built deflecting device with four small crosswise electromagnets; the whisker was placed at the intersection of the magnet axes. The results show that differences between responses to directional deflection were indicated by a change in the intrinsic optical signal of incident light at 546 nm corresponding to an increase in blood volume. Our results provide a preliminary indication that the different regions of the barrel have different directional preference, supporting recent electrophysiological studies suggesting that the barrel might have a fine, directionally-sensitive anatomical structure. PMID- 20304009 TI - Expression plasmids are only useful for the investigation of co-receptor tropism and fusion capacity of short HIV-1 envelope domains. AB - Expression vectors have been used widely to identify functionally important domains in HIV-1 glycoproteins. Env domains such as the V3 loop were amplified by polymerase chain reaction (PCR) and inserted into plasmids carrying the backbone of an HIV-1 reference strain like NL4-3. The hypothesis of the present approach was that cloning large domains of wild type envelopes yields constructs that are non-functional in co-receptor-expressing HeLaCD4 cells, in contrast to laboratory adapted HIV-1 strains. The background for this assumption was that primary HIV-1 virions are frequently less infectious and lack fusion capacity in HeLaCD4 cells compared to laboratory-adapted (LA) viruses. To address this hypothesis, env domains of different length were amplified from a panel of X4-tropic HIV-1 clinical isolates cultured in peripheral blood lymphocytes (PBLs) and cloned into the backbone of NL4-3 env. Constructs bearing either the V3 loops or 312 nucleotides of the intracellular trunk (ICT) of gp41 led to a similar fusion capacity as NL4-3. In contrast, none of the plasmids carrying the 2322 N-terminal nucleotides of primary isolates led to similar syncytium formation. These results have an effect on studies that investigate pathogenic effects of Env regions with chimeric constructs in the backbone of HIV reference envelopes. PMID- 20304010 TI - Validation of a loop-mediated isothermal amplification assay for visualised detection of wild-type classical swine fever virus. AB - Loop-mediated isothermal amplification (LAMP) is a nucleic acid amplification method applied and adapted to the detection of a number of pathogens. A LAMP assay was developed for the specific detection of wild-type classical swine fever virus (CSFV). Based on an alignment of genomic sequences of pestiviruses available in GenBank, four primers were selected targeting six positions in the NS5B gene region of the viral genome. The assay was performed in a simple water bath at a constant temperature of 62 degrees C, and after adding SYBR Green I, the results were visualised by the naked eye. This assay allowed easy applicability in a laboratory that is equipped simply, or even on site, close to the outbreaks and under field conditions. For confirmation, the results could also be visualised under UV light or by separation of the amplified products on 2% agarose gels. The detection limit of the assay was 2.5 medium tissue culture infectious dose (TCID(50)). The assay was validated with 116 clinical samples from vaccinated swineherds and 53 blood samples from experimental infections, and the results were comparable to a real-time RT-PCR assay. In summary, the LAMP assay provides a simple, rapid, and sensitive tool for the detection of wild-type CSFV under field conditions. PMID- 20304012 TI - Inhibition of replication of classical swine fever virus in a stable cell line by the viral capsid and Staphylococcus aureus nuclease fusion protein. AB - Classical swine fever (CSF) is one of the major diseases causing serious economic losses to the swine industry. To explore the feasibility of using capsid-targeted viral inactivation (CTVI) as an antiviral strategy against CSF infection, a plasmid pcDNA-Cap-SNase was constructed for expressing a fusion protein of CSFV capsid (Cap) and Staphylococcus aureus nuclease (SNase). Under G418 selection, a mammalian cell line PK-15 expressing stably the fusion protein Cap-SNase(PK 15/Cap-SNase) could be detected by rabbit antiserum against CSFV capsid protein and had good nuclease activity in cleaving linearized plasmid DNA. The CSFV titer produced from infection of this PK-15/Cap-SNase stable cell line was reduced by an order of 10(2)-10(3.5) or 70.8% compared to that produced in control PK-15 cells. Detection of the virus by ELISA indicated that CSFV propagation was inhibited in the PK-15/Cap-SNase cell line. It was demonstrated clearly that the fusion protein Cap-SNase could inhibit effectively the production of CSFV, resulting in a reduction in infectious titers. Therefore, CTVI may be valuable therapeutic approach against CSFV. PMID- 20304011 TI - Influenza virus-like particles as an antigen-carrier platform for the ESAT-6 epitope of Mycobacterium tuberculosis. AB - Various virus-like particles (VLPs) have been shown to induce cytotoxic T-cell immune response as well as B-cell immune response. This makes VLPs promising candidates for antigen-carrier platforms for various epitopes. Influenza A VLPs were produced displaying a 20 amino acid sequence from Mycobacterium tuberculosis early secretory antigenic target 6 protein (ESAT-6). As this sequence is known to comprise a potent T-cell epitope it was chosen as a model for a foreign epitope to be presented on an influenza VLP scaffold. The ESAT-6 epitope was engineered into the antigenic region B of the influenza hemagglutinin (HA) from strain A/New Caledonia/20/99. VLPs were expressed in insect cells and subjected to immunization studies in mice. High serum antibody titers detected against recombinant ESAT-6 demonstrated the feasibility of influenza A VLPs serving as an efficient platform for epitope presentation. PMID- 20304013 TI - Oligonucleotide microarray with a minimal number of probes for the detection and identification of thirteen genera of plant viruses. AB - A major challenge facing agriculture at present is the development of techniques that can screen field samples and other plant materials simultaneously for the presence of many viruses. Microarray techniques show promise in this regard, as their high throughput nature can potentially detect a range of viruses using a single test. In this paper we present an array that can detect a wide spectrum of 169 plant virus species from 13 different genera. The array was constructed using an automated probe design protocol which generated a minimal number of probes to detect viruses at the genus level. The designed arrays showed a high specificity and sensitivity when tested with a set of standard virus samples. Field samples collected from a severe disease outbreak of Panax notoginseng farms in Yunnan, China, in 2001 were screened, where a potyvirus infection was identified associated with the disease. PMID- 20304014 TI - Single-chain fragment variable antibody against the capsid protein of bovine immunodeficiency virus and its use in ELISA. AB - Recombinant antibody specific for the capsid (CA) protein of bovine immunodeficiency virus (BIV) was generated in the form of single-chain fragment variable (ScFv) using the phage display technique for affinity selection. The variable heavy (V(H)) and variable light (V(L)) chain gene fragments were recovered from cells of CA-specific hybridoma (9G10) described previously. The V(H) and V(L) DNA fragments were assembled through a flexible linker DNA to generate ScFv fragment which was cloned in a phagemid expression vector to express ScFv protein. The specific reactivity of the expressed ScFv to the CA antigen was confirmed by Western blot, and the ScFv fragment was used to develop a competitive inhibition ELISA for detection of antibodies to BIV in cattle and buffalo. The recombinant antibody was shown to be more than four times sensitive than its parent monoclonal antibody (MAb, 9G10) by testing of spiked samples of reference positive sera. The improved sensitivity of the recombinant antibody based ELISA was confirmed by the detection of a larger proportion of animals with BIV antibody by it than by the MAb-based ELISA. PMID- 20304015 TI - Development and optimisation of a duplex real-time reverse transcription quantitative PCR assay targeting the VP7 and NS2 genes of African horse sickness virus. AB - Nucleotide sequences of 52 South African isolates of African horse sickness virus (AHSV) collected during 2004-2005 and including viruses of all nine AHSV serotypes, were used to design and develop a duplex real-time reverse transcription quantitative PCR (RT-PCR) assay targeting the VP7 (S8) and NS2 (S9) genes of AHSV. The assay was optimized for detection of AHSV in fresh and frozen blood of naturally infected horses. Assay performance was enhanced using random hexamers rather than gene-specific primers for RT, and with denaturation of double-stranded RNA in the presence of random hexamers. The assay was efficient with a linear range of at least five orders of magnitude. The analytical sensitivity of the assay was 132 copies of the target genes (4125 copies per ml of blood), and the assay was at least 10-fold more sensitive than virus isolation on BHK-21 cells. The assay was also highly specific because it did not detect related orbiviruses, such as bluetongue and equine encephalosis viruses. PMID- 20304016 TI - Development of a rapid and comprehensive proteomics-based arboviruses detection system. AB - A rapid and comprehensive protocol, which combines simple purification and liquid chromatography-electrospray ionisation-tandem mass spectrometry (LC-ESI/MS/MS), was developed for identification of arboviruses in infected culture fluid. Using this protocol, various arboviruses were detected including uncommon viruses that were described previously as Banna virus and Yunnan orbivirus. This approach is useful for the rapid screening of viral samples that cannot be identified by conventional gene amplification or immunological methods. PMID- 20304017 TI - Simultaneous typing and HA/NA subtyping of influenza A and B viruses including the pandemic influenza A/H1N1 2009 by multiplex real-time RT-PCR. AB - Pandemic influenza A/H1N1 2009 and seasonal influenza viruses are currently co circulating worldwide. A rapid, sensitive, and specific assay for distinguishing pandemic influenza A/H1N1 2009 from seasonal influenza viruses and for subtyping seasonal influenza A viruses could aid in the surveillance and control of these viral infections. Here, such a multiplex real-time RT-PCR (rRT-PCR) assay for typing influenza A and B viruses and the pandemic influenza A/H1N1 2009 is developed. This assay can also subtype seasonal influenza A viruses simultaneously. The analytical sensitivity is 10-10(4) copies/reaction. The coefficients of variation of inter-assay and intra-assay are 0.04-0.45% and 0.08 0.97%, respectively. The new multiplex rRT-PCR assay is more sensitive in subtyping seasonal influenza viruses than the conventional PCR techniques. Results obtained with this assay for the detection of pandemic influenza A/H1N1 2009 are highly consistent (96.88%) with those achieved using the US CDC's rRT PCR protocol. A sample identified as "pandemic influenza A/H1N1 2009 positive" by the US CDC's rRT-PCR was reclassified correctly as subtype H3N2 using this assay. Taken together, this new multiplex rRT-PCR protocol could be an important tool for improving diagnosis and management of the pandemic influenza A/H1N1 2009 and seasonal influenza viruses. PMID- 20304019 TI - Tumor delivery of macromolecular drugs based on the EPR effect. AB - Enhanced permeability and retention (EPR) effect is the physiology-based principal mechanism of tumor accumulation of large molecules and small particles. This specific issue of Advanced Drug Delivery Reviews is summing up multiple data on the EPR effect-based drug design and clinical outcome. In this commentary, the role of the EPR effect in the intratumoral delivery of protein and peptide drugs, macromolecular drugs and drug-loaded long-circulating pharmaceutical nanocarriers is briefly discussed together with some additional opportunities for drug delivery arising from the initial EPR effect-mediated accumulation of drug containing macromolecular systems in tumors. PMID- 20304018 TI - Genetically engineered mannosylated-human serum albumin as a versatile carrier for liver-selective therapeutics. AB - Human serum albumin (HSA), a non-glycosylated protein, is widely employed as carrier for drug delivery systems. A series of recombinant, mannosylated-HSA mutants (Man-rHSAs: D63N, A320T and D494N) and their triple mutant (TM-rHSA: D63N/A320T/D494N) were prepared, that can be selectively delivered to the liver via mannose receptor (MR) on the liver non-parenchymal cells. A pharmacokinetic analysis of (111)In-Man-rHSAs in mice showed that they were rapidly cleared from the blood circulation, and were largely taken up by the liver rapidly in the order: TM-rHSA>D494N>>A320T=D63N, consistent with their degree of mannosylation. In vivo competition experiments with an excess amount of chemically modified Man BSA or mannan suggested that the hepatic uptake of TM-rHSA was selectively mediated by MR on Kupffer cells. Lastly, a TM-rHSA-NO conjugate, S-nitrosylated TM-rHSA, effectively delivered NO to the liver and then exhibited a significant inhibitory effect against hepatic ischemia/reperfusion injury model rats, accompanied by the induction of heme oxygenase-1. PMID- 20304020 TI - Differential effect of platelet activating factor on 1-methyl-4-phenylpyridinium induced cell death through regulation of apoptosis-related protein activation. AB - Platelet activating factor (PAF) has been suggested to play a critical role in the pathogenesis of neurological disorders. We assessed the effect of PAF against the toxicity of 1-methyl-4-phenylpyridinium (MPP(+)), a parkinsonian toxin, in relation to apoptotic process. PAF exhibited differential effect against the MPP(+) toxicity in differentiated PC12 cells depending on concentration. Treatment with 0.75 microM PAF significantly attenuated the MPP(+)-induced increase in Bax levels, decrease in Bid and Bcl-2 levels, and mitochondrial membrane potential loss that lead to the release of cytochrome c and subsequent caspase-3 activation. The inhibitory effect of PAF was not associated with nuclear factor-kappaB activation. In contrast, PAF at the concentrations greater than 2.5 microM exhibited a toxicity and additive effect on the MPP(+) toxicity. The results show that PAF at low concentrations, which does not induce a significant toxicity, may prevent the MPP(+) toxicity by suppressing the apoptosis-related protein activation and mitochondrial membrane permeability change that lead to the cytochrome c release and caspase-3 activation. The preventive effect seems to be associated with the inhibitory effect on the formation of reactive oxygen species and depletion of GSH. In contrast, PAF at higher concentrations may exhibit an additive toxic effect against the MPP(+) toxicity by increasing apoptosis-related protein activation. PMID- 20304022 TI - Auditory and visual P300 reflecting cognitive improvement in patients with schizophrenia with quetiapine: a pilot study. AB - We recorded event-related potentials (ERPs) in patients with schizophrenia before and after treatment with quetiapine, to investigate this drug's effects on cognitive function. Auditory and visual oddball stimulus discrimination paradigms were presented to patients with schizophrenia (N=20) before and after 3months' treatment with quetiapine. The 2-stimulus auditory oddball paradigm used a standard tone (1000Hz, 75dB, 80%) and a target tone (2000Hz, 75dB, 20%). The 2 stimulus visual oddball paradigm used a standard stimulus (small circle, 80%) and a target stimulus (large circle, 20%). Patients' severity of psychopathology was initially evaluated with the Positive and Negative Syndrome Scale (PANSS) and was likewise re-evaluated after treatment. After treatment with quetiapine, patients' P300 amplitudes increased over baseline for both tasks (auditory stimuli, P<0.01; visual stimuli, P<0.01) and their P300 latencies for both target stimuli decreased significantly (auditory stimuli, P<0.001; visual stimuli, P<0.01). Visual P300 amplitude was negatively correlated with the severity of positive symptoms at the Fz electrode before the treatment (r=-0.45, P<0.05). After treatment with quetiapine, there were no significant correlations between severity of positive or negative symptoms and visual P300 amplitudes for midline electrodes. These findings suggest that the reduced and delayed P300 may be a state marker for schizophrenia, which may in turn be modulated by positive symptoms, and also suggest that the amplitude and latency for both auditory and visual tasks may be decreased by quetiapine treatment. Based on these results, we suggest that the atypical antipsychotic quetiapine may improve some aspects of cognitive domains in patients with schizophrenia. PMID- 20304021 TI - Haplotype analysis of the interleukin-18 gene in Czech patients with allergic disorders. AB - The interleukin-18 (IL-18) gene on chromosome 11q22 has been suggested as a susceptibility factor for allergies. To test for a possible role of IL-18 polymorphisms in Czech population, case-control study including 958 subjects (633 allergic patients and 325 healthy controls) was performed. An allele-specific polymerase chain reaction was used to analyze variants at positions -607 C/A (rs1946518) and -137 G/C (rs187238) in the promoter region together with the polymerase chain reaction-restriction fragment length polymorphism method for the detection of polymorphism at position -140 C/G (previously -133 C/G, rs360721) in intron 1 of the IL-18 gene. The -1297 C/T (rs360719) polymorphism was genotyped by real-time-polymerase chain reaction, using a predevelopment TaqMan allele discrimination assay. There were no significant differences in distribution of alleles or genotypes in any of four single nucleotide polymorphisms in the IL-18 gene between controls and patients. However, subsequent analysis revealed a significant difference in haplotype frequencies between the allergic patients and healthy subjects (p < 0.01). Haplotype formed by -1297 C/-607 A/-137 C/-140 C alleles occurred significantly more frequently in patients than controls (0.0433 vs 0.0129; p < 0.0003; p(corr)< 0.01, OR = 3.37; 95% CI = 1.59-7.14). In contrast, there was no relationship among the IL-18 variants and total serum IgE level. Our results indicate that promoter polymorphisms in the IL-18 gene act in interaction and could play a role in allergic disorders. PMID- 20304023 TI - Changes of metabolic profiles in urine after oral administration of quercetin in rats. AB - Quercetin has been studied extensively. However, its actions in vivo are not well understood. We investigated the overall metabolic changes in urine after oral quercetin administration in rats and try to provide useful information on the actions of quercetin in vivo. Rats were orally administered a single dose of quercetin aglycon (40 mg/kg body weight). Urine samples were collected and subjected to (1)H nuclear magnetic resonance (NMR)-based metabolomic analysis and high performance liquid chromatography-mass spectrometry (HPLC-MS). Significant changes of metabolic profiles were observed in urine after quercetin administration. Relative increase in the concentrations of choline, creatinine, dimethylglycine, hippurate, taurine, trimethylamine N-oxide and reduction in acetate, alanine, lactate were observed. The concentrations of citrate, 2 oxoglutarate and succinate increased in the 0-24h period after treatment and decreased thereafter. Some peaks assignable to quercetin metabolites were found in the aromatic regions of (1)H NMR spectra. HPLC-MS analysis identified quercetin, methyl quercetin, quercetin sulfate, quercetin monoglucuronide, and methyl quercetin monoglucuronide in urine after administration of quercetin. Our current findings indicate that quercetin behaves not only as an antioxidant, but also a modulator for some metabolic processes in vivo. The active forms of quercetin present in the biofluids must be investigated further. PMID- 20304024 TI - Chromium and iron determinations in food and herbal plant samples by atomic absorption spectrometry after solid phase extraction on single-walled carbon nanotubes (SWCNTs) disk. AB - A preconcentration-separation procedure has been established based on solid phase extraction of Fe(III) and Cr(III) on single-walled carbon nanotubes (SWCNTs) disk. The analyte ions were quantitatively recovered at pH 8.0 on single-walled carbon nanotubes disk that contains 30 mg of nanotube. The influences of matrix components were tolerable. The detection limits for iron and chromium were calculated as 2.12 and 4.08 microg/l, respectively. The presented method was validated by the analysis of lichen (IAEA-336), CRM025-050 Metals on soil and BCR 032 Moroccan Phosphate rock certified reference materials. The method was successfully applied to the preconcentration and separation of iron and chromium in some food and herbal plant samples from Turkey. PMID- 20304025 TI - Prevention of lipopolysaccharide-induced mouse lethality by resveratrol. AB - The present study was undertaken to determine whether subacute treatment with resveratrol (RVT) protects mice against lipopolysaccharide (LPS)-induced oxidative stress and mortality as well as the mechanism involved in such protection. Mice were divided into three groups: control, LPS and LPS+RVT. Animals were pre-treated with RVT during 7 days. The survival rate was monitored over 48 h after LPS administration. Survival animals were sacrificed, their kidney, liver and brain homogenized for malondialdehyde (MDA), catalase (CAT) activity, free iron and nitric oxide (NO) determination. Plasma was also processed for transaminases, creatinine, urea, NO and iron measurement. Pre treatment with resveratrol greatly improved the survival rate of LPS-treated mice. Resveratrol counteracted LPS-induced tissue lipoperoxidation and catalase activity depletion. The polyphenol abrogated LPS-induced liver and kidney dysfunction as increased creatinine and urea as well as transaminases activities. In addition, pre-treatment with resveratrol abrogated LPS-induced tissues and plasma NO elevation and iron sequestration from plasma to tissue compartment. These data suggest that resveratrol prevents LPS-induced lethality and that its mode of action may involve differential iron deposition via iron shuttling proteins. PMID- 20304026 TI - Alaternin attenuates delayed neuronal cell death induced by transient cerebral hypoperfusion in mice. AB - The aim of this study was to determine whether alaternin exhibits neuroprotective activity after transient cerebral hypoperfusion induced by bilateral common carotid artery occlusion (BCCAO). Mice were subjected to BCCAO, and circulation was restored after 20 min. Alaternin (10 mg/kg, p.o) treatment significantly prevented nitrotyrosine and lipid peroxidation, as well as BCCAO induced inducible nitric oxide synthase (iNOS) expression. Alaternin also significantly reduced microglial activation (a marker of inflammation). The number of viable neurons detected by Nissl staining increased with alaternin (10 mg/kg, p.o) treatment at 7 days post-BCCAO. In the passive avoidance task, alaternin significantly ameliorated BCCAO-induced cognitive impairments (P<0.05). These results suggest that the neuroprotective effects of alaternin are mediated by its anti-inflammatory and radical scavenging activities. PMID- 20304027 TI - Determination of total mercury in chicken feed, its translocation to different tissues of chicken and their manure using cold vapour atomic absorption spectrometer. AB - In this study, the contents of total mercury (Hg) present in poultry feed, tissues of broiler chicken and manure were assessed. For this purpose, chicken feeds (five brands), different tissues of broiler chicken of two age groups (1-3 and 4-6 week) and manure samples were collected from five commercial poultry farms of Hyderabad, Pakistan. The Hg concentrations in feeds, chicken tissues (leg, muscle, liver and heart) and manure samples were determined by CVAAS, prior to microwave assisted acid digestion in closed vessels. For validation, a certified reference material, DORM-2 was used. The limit of detection and quantitation were 0.117 and 0.382 microg/kg, respectively The Hg concentration in different chicken feed were found in the range of 8.57-16.5 microg/kg. The concentration of Hg in chicken tissues were found in the range of 2.54-5.54 microg/kg (liver), 1.27-3.86 microg/kg (muscles) and 2.13-3.27 microg/kg (heart). The bioaccumulation factors (BAF) for Hg in different tissues were found in the range of 0.092-0.269. The obtained data shows the high correlation coefficient between feed and manure, while low r-values were obtained between Hg levels in feed and tissues of broiler chicken of two age groups. PMID- 20304028 TI - Antioxidant and antimicrobial properties of Moltkia petraea (Tratt.) Griseb. flower, leaf and stem infusions. AB - Antioxidant and antimicrobial activities as well as the quantity of phenolic substances (total phenol, flavonoid and phenolic acid contents) were determined in aqueous extracts of leaves, stems and flowers of Moltkia petraea (Tratt.) Griseb. from two mountainous localities (Sveti Jure and Snijeznica) in Croatia. In addition, the profile of phenolic acids was analyzed by UPLC-MS/MS. Antioxidant activities of all extracts in different test systems, namely the DPPH radical scavenging, reducing power assay and chelating activity, increased with extract concentration. Activity of the extracts from Snijeznica in beta-carotene linoleic acid assay did not differ from the activity of standard, BHA. The leaf extracts from Snijeznica demonstrated superior antioxidant activity in most of the assays, while the stem extract from the same locality was the most effective Fe(2+) ion chelator. In general, the extracts from Snijeznica were more effective antioxidants than the corresponding extracts from Sveti Jure. The aqueous extracts of M. petraea did not show antimicrobial activity against bacteria and fungi tested in the diffusion and dilution assays. PMID- 20304029 TI - Tyrosine phosphorylation of SHIP promotes its proteasomal degradation. AB - OBJECTIVE: The activity of the SH2-containing-phosphatidylinositol-5'-phosphatase (SHIP, also known as SHIP1), a critical hematopoietic-restricted negative regulator of the PI3 kinase (PI3K) pathway, is regulated in large part via its protein levels. We sought to determine the mechanism(s) involved in its downregulation by BCR-ABL and by interleukin (IL)-4. MATERIALS AND METHODS: We used Ba/F3(p210-tetOFF) cells to study the downregulation of SHIP by BCR-ABL and bone marrow-derived macrophages to study SHIP's downregulation by IL-4. RESULTS: We show herein that BCR-ABL downregulates SHIP, but not SHIP2 or PTEN, and this can be blocked with the Src kinase inhibitor PP2, which inhibits the tyrosine phosphorylation of SHIP, or with the proteasomal inhibitor MG-132. We also show, using anti-SHIP immunoprecipitates, that c-Cbl and Cbl-b are associated with SHIP and that BCR-ABL induces SHIP's polyubiquitination. This ubiquitination can be blocked with PP2, consistent with the tyrosine phosphorylation of SHIP acting as a signal for its ubiquitination. In bone marrow-derived macrophages, IL-4 also leads to the proteasomal degradation of SHIP but, unlike in Ba/F3(p210-tetOFF) cells, SHIP2 is also proteasomally degraded and the degradation of both inositol phosphatases can be prevented with PP2 or MG-132. CONCLUSION: Our results suggest that SHIP protein levels can be reduced via BCR-ABL and/or Src family member induced tyrosine phosphorylation of SHIP because this triggers its polyubiquitination and degradation within the proteasome. PMID- 20304030 TI - MAP1B binds to the NMDA receptor subunit NR3A and affects NR3A protein concentrations. AB - Incorporation of the N-methyl-d-aspartate receptor (NMDAR) subunit NR3A into functional NMDARs results in reduced channel conductance and Ca(2+) permeability. To further investigate the function of NR3A, we have set out to characterize its intracellular binding partners. Here, we report a novel protein interaction between NR3A and microtubule associated-protein (MAP) 1B, which both are localized to dendritic shafts and filopodia. NR3A protein levels were increased in MAP1B deficient (-/-) mice, with a corresponding decrease in NR1 levels, but the fraction of filopodia immunoreactive for NR3A was equal in cells from -/- and wild type (WT) mice. NR3A has previously been shown to interact with another member of the MAP1 family, MAP1S. We showed that MAP1S binds to microtubules in a similar manner as MAP1B, and suggest that MAP1S and MAP1B both are involved in regulating trafficking of NR3A-containing NMDAR. PMID- 20304031 TI - Early event-related potentials changes during simple mental calculation in Chinese older adults with mild cognitive impairment: A case-control study. AB - The aim was to examine early event-related potential (ERP) changes during mental arithmetic calculation task in mild cognitive impairment patients compared to healthy elderly. 16 mild cognitive impairment (MCI) subjects and 16 healthy Chinese older adults were studied. Event-related potentials were elicited using a simple mental calculation task. Performance on arithmetic calculation task, and the latency and amplitude of early event-related potential components (N1, P1, N170, and P2) were compared between the two groups. The reaction time of MCI group was significantly longer than that of control group (1691.03+/-94.59 vs. 1539.55+/-27.76, P<0.01). The correct rate of MCI group (0.9463+/-0.04) was significantly lower than that of control group (0.9776+/-0.02, P<0.01). The latency of temporal-occipital N170 and central-prefrontal P2 of MCI group were significantly prolonged compared to controls. MCI subjects presented significantly higher P2 amplitude. Compared with healthy controls, N170 was significantly lower at left temporal-occipital region and higher at right temporal-occipital region in mild cognitive impairment. Mild cognitive impairment patients had deficit on simple calculation. The early arithmetic calculation processing mechanism of mild cognitive impairment patients may be different from normal people. PMID- 20304032 TI - Acute hypoxia promote the phosphorylation of tau via ERK pathway. AB - Tau phosphorylation and hypoxia are both linked to the pathology of Alzheimer's disease. To find out the possible connection between hypoxia and tau phosphorylation, we performed this study to evaluate the level of phosphorylated tau under hypoxic or normal condition. We found in our study that hypoxia promoted the phosphorylation of tau protein via ERK pathway, which suggest hypoxia might be involved in the process of tau pathology. PMID- 20304034 TI - Galactose specific adhesin of enteroaggregative E. coli induces IL-8 secretion via activation of MAPK and STAT-3 in INT-407 cells. AB - BACKGROUND: Enteroaggregative Escherichia coli (EAEC) is one of the most common bacterial pathogens associated with the etiology of persistent diarrhea. A characteristic feature of EAEC-pathogenesis is the induction of profound inflammatory response in the intestinal epithelium. The present study was designed to investigate the underlying mechanism of inflammatory responses induced by a novel galactose specific adhesin of T7 strain of EAEC (EAEC-T7) in human intestinal epithelial cell line (INT-407). METHODS: INT-407 cells were stimulated with the adhesin in the absence and presence of anti-adhesin (IgG(AD))/d-galactose/H7/staurosporin (inhibitor of PKC)/PD098059 (inhibitor of MEK)/SB203580 (inhibitor of p38-MAPkinase)/AG490 (inhibitor of JAK (-2,-3)/STAT-3 pathway). The expression of activated Raf-1, MEK-1, ERK1/2, JNK, p38-MAPK and STAT-3 was analyzed by Western immunoblot. Release of interleukin-8 (IL-8) was measured by ELISA. RESULTS: The adhesin was found to induce activation of Raf-1, MEK-1, ERK1/2, p38-MAPK and STAT-3, which was reduced in the presence of IgG(AD)/d-galactose. The activation of Raf-1 was found to be attenuated in the presence of H7/staurosporin. The expression of phosphorylated STAT-3 was downregulated in the presence of AG490 and PD098059. Further, the adhesin induced IL-8 secretion was reduced in the presence of the inhibitors of MEK (PD098059), p38-MAPK (SB203580) and JAK (-2,-3)/STAT-3 pathway (AG490). CONCLUSIONS: We propose that STAT-3 activation is quintessential for the galactose specific adhesin induced IL-8 secretion by INT-407 cells and must occur in concert with the activation of ERK1/2. GENERAL SIGNIFICANCE: Our contribution regarding the galactose specific adhesin mediated signaling leads to an improved understanding of the EAEC-pathogenesis and may provide novel therapeutic approaches to combat EAEC infection. PMID- 20304035 TI - Structure-function relationships in the context of reinforcement-related learning: a combined diffusion tensor imaging-functional magnetic resonance imaging study. AB - In the context of probabilistic learning, previous functional magnetic resonance imaging studies have shown decreasing uncertainty accompanying decreasing neuronal activation in task-relevant networks. Moreover, initial evidence points to a relationship between white matter structure and cognitive performance. Little is known, however, about the structural correlates underlying individual differences in activation and performance in the context of probabilistic learning. This combined functional magnetic resonance imaging-diffusion tensor imaging study aimed at investigating the individual ability to reduce processing resources with decreasing uncertainty in direct relation to individual characteristics in white matter brain structure. Results showed that more successful learners, as compared with less successful learners, exhibited stronger activation decreases with decreasing uncertainty. An increased mean and axial diffusivity in, among others, the inferior and superior longitudinal fasciculus, the posterior part of the cingulum bundle, and the corpus callosum were detectable in less successful learners compared with more successful learners. Most importantly, there was a negative correlation between uncertainty related activation and diffusivity in a fronto-parieto-striatal network in less successful learners only, indicating a direct relation between diffusivity and the ability to reduce processing resources with decreasing uncertainty. These findings indicate that interindividual variations in white matter characteristics within the normal population might be linked to neuronal activation and critically influence individual learning performance. PMID- 20304036 TI - Natriuretic peptide receptors are expressed in rat retinal ganglion cells. AB - Natriuretic peptides (NPs) exert their actions through three membrane-bound receptors, which are known as NP receptors (NPRs: NPR-A, NPR-B and NPR-C). In this work we examined the expression of three NPRs in rat retinal ganglion cells (GCs), retrogradely labeled and intracellularly dye-injected, by double immunofluorescence labeling. In vertical sections, almost all GCs, retrogradely labeled by cholera toxin B, were stained by antibodies against the three NPRs. The labeling for three NPRs was observed mainly on the membranes of the somata of GCs, whereas the staining for NPR-A was also seen in the cytoplasm. Moreover, with tangential sections, almost all cells located in the ganglion cell layer were NPR-A, B, C immunoreactive. By combining with intracellular injection of Neurobiotin into GCs in whole mount retinas that enables to identify ON-, OFF- and ON-OFF-types of GCs according to arborization of their dendrites in the inner plexiform layer, we further demonstrated that NPRs were expressed in these major types of GCs. PMID- 20304033 TI - Serum ferritin: Past, present and future. AB - BACKGROUND: Serum ferritin was discovered in the 1930s, and was developed as a clinical test in the 1970s. Many diseases are associated with iron overload or iron deficiency. Serum ferritin is widely used in diagnosing and monitoring these diseases. SCOPE OF REVIEW: In this chapter, we discuss the role of serum ferritin in physiological and pathological processes and its use as a clinical tool. MAJOR CONCLUSIONS: Although many aspects of the fundamental biology of serum ferritin remain surprisingly unclear, a growing number of roles have been attributed to extracellular ferritin, including newly described roles in iron delivery, angiogenesis, inflammation, immunity, signaling and cancer. GENERAL SIGNIFICANCE: Serum ferritin remains a clinically useful tool. Further studies on the biology of this protein may provide new biological insights. PMID- 20304037 TI - IFN-gamma-mediated upmodulation of MHC class I expression activates tumor specific immune response in a mouse model of prostate cancer. AB - De novo expression of B7-1 impaired tumorigenicity of TRAMP-C2 mouse prostate adenocarcinoma (TRAMP-C2/B7), but it did not elicit a protective response against TRAMP-C2 parental tumor, unless after in vitro treatment with IFN-gamma. TRAMP-C2 cells secrete TGF-beta and show low MHC-I expression. Treatment with IFN-gamma increased MHC-I expression by induction of some APM components and antagonizing the immunosuppressant activity of TGF-beta. Thus, immunization with TRAMP-C2/B7 conferred protection against TRAMP-C2-derived tumors in function of the IFN-gamma mediated fine-tuned modulation of either APM expression or TGF-beta signaling. To explore possible clinical translation, we delivered IFN-gamma to TRAMP-C2 tumor site by means of genetically engineered MSCs secreting IFN-gamma. PMID- 20304038 TI - EV71: an emerging infectious disease vaccine target in the Far East? AB - Hand, foot, and mouth disease (HFMD) is a common viral illness in infants and children caused by viruses that belong to the enterovirus genus of the picornavirus family. Although most HFMD do not result in serious complications, outbreaks of HFMD caused by enterovirus 71 (EV71) can present with a high rate of neurological complications, including meningoencephalitis, pulmonary complications, and possibly death. HFMD caused by EV71 has become a major emerging infectious disease in Asia and the highly pathogenic potential of EV71 clearly requires the attention of world medical community. Although vaccine development for EV71 is active and ongoing in Asian countries, a greater joint effort is needed for vaccine researchers and developers in both developed and developing countries to produce a safe and effective EV71 vaccine. PMID- 20304039 TI - Estrogenic and serotonergic butenolides from the leaves of Piper hispidum Swingle (Piperaceae). AB - ETHNOPHARMACOLOGICAL RELEVANCE: Our previous work has demonstrated that several plants in the Piperaceae family are commonly used by the Q'eqchi Maya of Livingston, Guatemala to treat amenorrhea, dysmenorrhea, and pain. Extracts of Piper hispidum Swingle (Piperaceae), bound to the estrogen (ER) and serotonin (5 HT7) receptors. AIM OF THE STUDY: To investigate the estrogenic and serotonergic activities of Piper hispidum extracts in functionalized assays, identify the active chemical constituents in the leaf extract, and test these compounds as agonists or antagonists of ER and 5-HT7. MATERIALS AND METHODS: The effects of the Piper hispidum leaf extracts were investigated in estrogen reporter gene and endogenous gene assays in MCF-7 cells to determine if the extracts acted as an estrogen agonist or antagonist. In addition, the active compounds were isolated using ER- and 5-HT7 receptor bioassay-guided fractionation. The structures of the purified compounds were identified using high-resolution LC-MS and NMR spectroscopic methods. The ER- and 5-HT7-agonist effects of the purified chemical constituents were tested in a 2ERE-reporter gene assay in MCF-7 cells and in serotonin binding and functionalized assays. RESULTS: Three butenolides including one new compound (1) were isolated from the leaves of Piper hispidum, and their structures were determined. Compound 1 bound to the serotonin receptor 5-HT(7) with IC(50) values of 16.1 and 8.3 microM, respectively, and using GTP shift assays, Compound 1 was found to be a partial agonist of the 5-HT(7) receptor. The Piper hispidum leaf extracts, as well as Compounds 2 and 3 enhanced the expression of estrogen responsive reporter and endogenous genes in MCF-7 cells, demonstrating estrogen agonist effects. CONCLUSIONS: Extracts of Piper hispidum act as agonists of the ER and 5-HT(7) receptors. Compound 1, a new natural product, identified as 9,10-methylenedioxy-5,6-Z-fadyenolide, was isolated as the 5-HT(7) agonist. Compounds 2 and 3 are reported for the first time in Piper hispidum, and identified as the estrogen agonists. No inhibition of CYP450 was observed for any of these compounds in concentrations up to 1 microM. These activities are consistent with the Q'eqchi traditional use of the plant for the treatment of disorders associated with the female reproductive cycle. PMID- 20304040 TI - Antinociceptive effect of Zanthoxylum rhoifolium Lam. (Rutaceae) in models of acute pain in rodents. AB - AIM OF THE STUDY: Zanthoxylum rhoifolium Lam. (Rutaceae) is locally known as "mamica de cadela", and its bark is popularly used for toothache and earache. The objective of this study was to investigate the antinociceptive effect of the ethanolic extract from this species' stem bark (EtOH), its fractions of partition (hexane-HEX, ethyl acetate-AcOEt, aqueous-AQ) and lupeol (a triterpene obtained from HEX) in models of acute pain. MATERIALS AND METHODS: Male and female Swiss mice (25-35 g, n=6-12 animals/group) were used to assess acute toxicity and nociception (Animal Ethics Committee/UFPI, No. 09/2008). Acute toxicity was studied up to 2 g/kg p.o. of EtOH. In the formalin test (2%, 20 microL/paw), the licking time of the stimulated paw was quantified during the first 5 min (first phase) and at 15-30 min (second phase), 1h after oral treatment with EtOH, HEX, AcOEt or saline, and 30 min after use of morphine-MOR (5 mg/kg i.p.). The same response evoked by capsaicin (2 microg/20 microL/paw) was quantified during 5 min, after administration of EtOH, HEX, AcOEt, AQ, saline and MOR. The licking time of the paw that was stimulated with glutamate (10 micromol/20 microL) was measured (15 min) after treatment with EtOH, HEX, AcOEt, AQ, lupeol, saline or MK801 (0.03 mg/kg, i.p.). Mice were submitted to the rota-rod task and open-field test in order to assess any non-specific muscle-relaxant or sedative effects of EtOH (250 mg/kg p.o.) and HEX (500 mg/kg p.o.). RESULTS: The animals did not exhibit any acute toxicity to EtOH (up to 2 g/kg p.o.), so it was not possible to calculate the LD50. EtOH, HEX and AcOEt (62.5-250 mg/kg) produced a significant antinociceptive effect in the formalin and capsaicin tests. However, AQ was ineffective. EtOH, HEX, AcOEt and lupeol reduced the glutamate-evoked nociceptive response, but AQ had no effect. EtOH and HEX did not alter the locomotion of animals in the open-field or rota-rod tests, which suggest a lack of a central depressant effect. CONCLUSION: The results confirm the popular use of Zanthoxylum rhoifolium as an analgesic, and contribute to the pharmacological knowledge of this species because it was shown that EtOH and its less polar partition fractions (HEX, AcOEt) have an antinociceptive effect in models of chemical nociception, and that lupeol appears to be one of the constituents responsible for this effect. PMID- 20304041 TI - Ovarian status influenced the rate of body-weight change but not the total amount of body-weight gained or lost in female CBA/J mice. AB - Previously we reported that prepubertally ovariectomized mice that received young, transplanted ovaries at a postreproductive age displayed a 40% increase in life expectancy. To study this increase in life expectancy in greater detail, prepubertally ovariectomized and ovary-intact CBA/J mice underwent ovarian transplantation at 11 months with 60-day-old ovaries or a sham surgery. Life span was significantly increased in transplant recipients. Body-weight changes of mice in each group were measured from the time of surgery (11 months) to death. Neither ovariectomy nor ovarian transplantation influenced the amount of peak body-weight attained or body-weight retained at death. However, the time (days) to peak body-weight was decreased by ovariectomy and ovarian transplant recipients displayed a trend toward an increase in time to peak weight. In addition, ovarian transplantation decreased the rate of weight loss to death. These results demonstrate that ovarian status, examined by means of ovariectomy and ovarian transplantation, clearly influenced the rate of weight change, but not the total amount of weight gain or loss in female mice. PMID- 20304042 TI - Development of a rapid screening and surveillance for estrogenic chemicals in environment based on recombinant yEGFP yeast cell. AB - A recombinant yEGFP gene yeast strain necessary for the routine screening of estrogen activity in the chemical product of the environment was described. Two plasmids, one containing human estrogen receptor (hER) cDNA fused to the GPD gene promoter and another yEGFP inserted under the control of ERE, were constructed. The use of hER cDNA and the yEGFP reporter in the yeast cell sensor resulted in estrogenic chemical product-dependent light emission of yEGFP without additions owing its advantages: a simple and reagent-free measurement of GFP, and a non toxic protein characteristic. The time needed for the optimal induction of light emission was 4h. The maximal fold induction of 8.80 over uninduced levels at the concentration of 10(-5)M of bisphenol A and 0.1 nM sensitivities for four different estrogenic chemicals tested were obtained. Five different chemicals which could not bind to hER did not cause an induction of yEGFP. This bioassay can be performed completely in 96-well plates. Thus, this test system can be used as a rapid screening system for the surveillance of estrogenic chemical products in the environment. The yEGFP assay is sensitive, reproducible, and cheap, which makes it highly suitable to be used as a high throughput system. PMID- 20304043 TI - Prolyl endopeptidase mRNA expression in the central nervous system during rat development. AB - Prolyl endopeptidase (PEP) is a serine protease that cleaves small peptides at the carboxyl side of L-proline. PEP has been reported to have important functions in the brain being implicated in learning and memory processes, psychological disorders and neurodegenerative diseases. Several PEP substrates have been shown to play a role during brain development and this observation led us to investigate the expression of PEP mRNA in the rat brain and spinal cord, from embryo to adult stages. In situ hybridization revealed that PEP mRNA is expressed early, from embryonic day 15, notably in germinative areas including the neocortical, hippocampal, pallidal, thalamic, anterior hypothalamic, tectal, cerebellar, pontine and medullary neuroepithelia. PEP mRNA was also found in the differentiating fields of the olfactory bulb, the orbital and cingulate cortex, the hippocampal formation, the cortical plate and the subventricular zone of the cortex. Quantitative RT-PCR analysis in various brain areas and the spinal cord showed that PEP mRNA levels are more abundant during the perinatal stages, coinciding with a period of neuronal migration and differentiation. From then on, PEP mRNA expression decreased, reaching its lowest levels at adulthood. Overall, the present data support the possibility that PEP exerts specific functions related to neurodevelopment besides those proposed to date. PMID- 20304044 TI - Detection of nitric oxide by electron paramagnetic resonance spectroscopy. AB - Electron paramagnetic resonance (EPR) spectroscopy has been used in a number of ways to study nitric oxide chemistry and biology. As an intrinsically stable and relatively unreactive diatomic free radical, the challenges of detecting this species by EPR are somewhat different from those of transient radical species. This review gives a basic introduction to EPR spectroscopy and discusses its uses to assess and quantify nitric oxide formation in biological systems. PMID- 20304045 TI - Pro-oxidant activity of apocynin radical. AB - Apocynin has been widely used as an NADPH oxidase inhibitor in many experimental models. However, concern regarding the efficacy, selectivity, and oxidative side effects of the inhibitor is increasing. In this study, our aim was to characterize the pro-oxidant properties of apocynin and the structurally-related compounds vanillin and vanillic acid. Glutathione (GSH), cysteine, ovalbumin, and the coenzyme NADPH were chosen as potential target biomolecules that could be affected by transient free radicals from apocynin, vanillin and vanillic acid. Additionally, trolox and rifampicin were used as models of hydroquinone moieties, which are particularly susceptible to oxidation. Transient radicals were generated by horseradish peroxidase/hydrogen peroxide-mediated oxidation. In the presence of apocynin, oxidation of GSH was increased seven-fold, and the product of this reaction was identified as GSSG. Similar results were obtained for oxidation of cysteine and ovalbumin. Oxidation of the coenzyme NADPH increased more than 100-fold in the presence of apocynin. Apocynin also caused rapid oxidation of trolox and rifampicin to their quinone derivatives. In conclusion, the pro-oxidant activity of apocynin is related to its previous oxidation leading to transient free radicals. This characteristic may underlie some of the recent findings regarding beneficial or deleterious effects of the phytochemical. PMID- 20304046 TI - Regeneration capability of Lin-/c-Kit+/Sca-1+ cells with or without radiation exposure for repopulation of peripheral blood in lethally irradiated mice monitored using Ly5.1 isotype on days 35, 90, and 270 after transplantation. AB - OBJECTIVE: Hematopoietic stem cells are supposed to repopulate and maintain long term regeneration of the recipient's bone marrow and peripheral blood. In this study, we evaluated the regeneration capability of Lin(-)/c-Kit(+)/Sca-1(+) (LKS) cells, the putative hematopoietic stem cells, after radiation exposure at graded doses, for long-term regeneration of peripheral blood in lethally irradiated recipients. MATERIALS AND METHODS: LKS primitive progenitor cells, collected from the bone marrow of Ly5.1 mice that had been irradiated at graded increased doses (0.5, 1, 1.5, and 2 Gy) were transfused into lethally irradiated (9.5 Gy) Ly5.2 mice. Then, the Ly5.1 chimeric ratio in repopulated peripheral blood cells in the recipients was monitored. A reactive oxygen species (ROS)-reacting CM-H(2)DCFDA dye was used to evaluate the amount of ROS in LKS primitive progenitor cells with/without irradiation. Moreover, the amount of intracytoplasmic ROS generated after irradiation was estimated in terms of percent attenuation of cellular increase in number by the treatment with 100 microM N-acetyl-L-cysteine before irradiation. RESULTS: Differential regeneration capability of LKS cells irradiated at graded increased doses showed a dose-dependent suppression of regeneration of peripheral blood in the recipient mice as compared with LKS cells without radiation exposure. The amount of intracytoplasmic ROS in LKS cells was much smaller than that in mature bone marrow cells, and that of ROS in LKS increased slightly after radiation exposure, as evaluated by CM-H(2)DCFDA dye fluorescence analysis. The estimated amount of ROS generated in LKS cells after radiation exposure was different between progenitor cells for early regeneration and those for late regeneration; namely, the amount of ROS in progenitors on day 270 were estimated to be smaller than that in progenitors for day 35 or day 90. CONCLUSIONS: Because of the small amount of generated radiation-induced ROS calculated in terms of attenuation rate after N-acetyl-L-cysteine treatment, progenitor cells regenerating peripheral blood cells 270 days after transfusion were assumed to be anaerobic and more immature and radioresistant than those on day 35 or day 90. However, limited long-term regeneration capability (up to 270 days) of steady-state LKS cells than that of unfractionated rescue bone marrow cells suggests that LKS cells do not seem to be true hematopoietic stem cells. PMID- 20304047 TI - Prenatal MDMA exposure delays postnatal development in the rat: a preliminary study. AB - 3,4-methylenedioxymethamphetamine or MDMA (ecstasy) is a synthetic illicit drug which is widely consumed throughout the world. Drug abuse during pregnancy may have an impairing effect on the progeny of drug-abusing mothers. The purpose of the present study was to assess the effect of prenatal MDMA exposure on the progeny development, using a rat model. Pregnant animals were injected daily with MDMA (10 mg/kg) between the 13th and 20th days of gestation. Male and female pups were then tested throughout the lactation period on the appearance and improvement of physical and sensory motor parameters. Appearance of some physical features (eyes opening and incisor eruption) and neurological reflexes as well as improving performances in negative geotaxis, gait and inclined board tests were delayed in pups prenatally exposed to MDMA compared to saline-treated pups. In contrast, functions that are necessary for survival such as forelimb reflex (that enables suckling) were present in both groups. At four weeks of age, MDMA animals recovered to normal level in all studied parameters. The delay in physical and neurological reflex development could be interpreted as alterations in maturation of some neuronal circuitries induced by prenatal MDMA exposure. PMID- 20304048 TI - Microemulsion formulations for the transdermal delivery of testosterone. AB - The objective was to develop a microemulsion formulation for the transdermal delivery of testosterone. Microemulsion formulations were prepared using oleic acid as the oil phase, Tween20 as a surfactant, Transcutol as cosurfactant, and water. The microemulsions were characterized visually, with the polarizing microscope, and by dynamic light scattering. In addition, the pH, conductivity (sigma) and viscosity (eta) of the formulations were measured. Moreover, differential scanning calorimetry and diffusion-ordered nuclear magnetic resonance spectroscopy were used to study the formulations investigated. Conductivity measurements revealed, as a function of the weight fraction of the aqueous phase, the point at which the microemulsion made the transition from water-in-oil to bicontinuous. Alterations in the microstructure of the microemulsions, following incorporation of testosterone, have been evaluated using the same physical parameters (pH, sigma and eta) and via Fourier-transform infrared spectroscopy (FT-IR), (1)H NMR and (13)C NMR. These methods were also used to determine the location of the drug in the colloidal formulation. Finally, testosterone delivery from selected formulations was assessed across porcine skin in vitro in Franz diffusion cells. The physical parameter determinations, combined with the spectroscopic studies, demonstrated that the drug was principally located in the oily domains of the microemulsions. Testosterone was delivered successfully across the skin from the microemulsions examined, with the highest flux achieved (4.6+/-0.6microgcm(-2)h(-1)) from a formulation containing 3% (w/v) of the active drug and the composition (w/w) of 16% oleic acid, 32% Tween20, 32% Transcutol and 20% water. The microemulsions considered offer potentially useful vehicles for the transdermal delivery of testosterone. PMID- 20304049 TI - Delivery of DNA-based cancer vaccine with polyethylenimine. AB - DNA-based vaccine directed to tumor-specific antigens is an attractive strategy in cancer prevention and therapy. In view of the poor immunogenicity of most tumor-associated antigens, studies were carried out here to examine the adjuvant effect of polyethylenimine (PEI), a cationic polymer widely used in non-viral gene delivery, on the efficacy of cancer vaccine strategy. Treatment of animals with the DNA/PEI complexes resulted in antigen-specific cell lysis and activation of B3Z cells, an ovalbumin/K(b)-specific cytotoxic clone that recognizes the target cells through the class I major histocompatibility complex (MHC) molecules. Immunohistochemical examination showed that PEI-mediated DNA vaccination induced cell death and significant lymphocyte infiltration at the injection sites. Immunization of C57BL/6J mice with the DNA/PEI complexes either preceded or after tumor cell inoculation suppressed tumor growth and prolonged the survival rate of the animals. Results obtained in this study illustrated the potential use of PEI as an adjuvant in DNA-based cancer vaccination for induction of protective and therapeutic immunity. PMID- 20304050 TI - Active packaging for topical cosmetic/drug products: a hot-melt extruded preservative delivery device. AB - A delivery device intended for the prolonged release of antimicrobial agents, able to enhance the stability profile of liquid/semi-solid cosmetic/pharmaceutical products for topical application, was proposed in the present study. With the aid of a simulation program based on compartment models, the relevant kinetic and formulation parameters were defined using dehydroacetic acid sodium salt (DHA.Na, Prevan) as the model preservative. Indeed, the overall DHA.Na degradation rate is increased in the presence of formaldehyde releasers that are often employed as co-preservatives. Inert matrices (3 g weight and 18 mm diameter) based on high-density polyethylene (HDPE), possibly consistent with the design of an active packaging meant for preservative delivery, were prepared by hot-melt extrusion. Units with satisfactory physical-technological properties could be obtained up to 50%w/w loads of antimicrobial agent. In an attempt to modify the relevant Fickian release profiles by varying the area exposed to the medium, matrix systems coated with an impermeable film except for one base (CMs) or for the inner surface of a central drilled hole (PCMs) were investigated. On the basis of the n exponent of power equation and the outcome of linear fitting, PCMs were proven able to yield the zero-order release behaviour needed to ensure constant DHA.Na levels over a predetermined time period, as indicated by the simulation process. PMID- 20304051 TI - Vitamin D supplementation suppresses age-induced bone turnover in older women who are vitamin D deficient. AB - There is a lack of evidence that improving vitamin D status, without changing calcium intake, has a positive effect on bone turnover as indicated by bone marker changes. The objective was to measure the effect of vitamin D supplementation, in vitamin D deficient women (25(OH)D concentration<50 nmol/L), on osteocalcin (OC) and C-telopeptide (CTX). The study design was a randomised controlled intervention administering 4000 IU vitamin D3 or placebo daily for 6 months to South Asian women, aged>20 years. Subjects were stratified by age and menopausal status. Median (25th, 75th percentile) serum 25(OH)D increased significantly from 21 (11, 40) to 75 (55, 84) nmol/L with supplementation. In women>49 years or postmenopausal (n=26), who were not supplemented (n=13), CTX and OC levels increased (P=0.001, P=0.004 respectively), indicating an increased rate of bone turnover. With supplementation CTX decreased (P=0.012) and there was no significant change in OC. In women who were under 49 years and premenopausal (n=55; 29 supplemented), there was no significant response to supplementation in either CTX or OC. We conclude that correcting vitamin D deficiency in older women suppresses the age-induced increase in bone turnover and reduces bone resorption which would normally be exacerbated in conditions of low serum 25(OH)D. PMID- 20304052 TI - Gemini vitamin D analog suppresses ErbB2-positive mammary tumor growth via inhibition of ErbB2/AKT/ERK signaling. AB - Numerous synthetic vitamin D analogs have been studied for their effects on the prevention and treatment of breast cancer. However, the inhibitory effects of naturally occurring 1alpha,25-dihydroxyvitamin D3 or its synthetic analogs on ErbB2 overexpressing mammary tumorigenesis have not been reported. Gemini vitamin D analogs are novel synthetic vitamin D derivatives with a unique structure of two six-carbon chains at C-20. We have previously shown that Gemini vitamin D analogs significantly inhibited carcinogen-induced estrogen receptor (ER) positive mammary tumorigenesis and reduced ER-negative MCF10DCIS.com xenograft tumor growth without hypercalcemic toxicity. In the present study, we have determined the inhibitory effect of a potent Gemini vitamin D analog BXL0124 (1alpha,25-dihydroxy-20R-21(3-hydroxy-3-deuteromethyl-4,4,4-trideuterobutyl)-23 yne-26,27-hexafluoro-cholecalciferol) on the ErbB2/Her-2/neu overexpressing mammary tumorigenesis. The Gemini BXL0124 inhibits ErbB2-positive mammary tumor growth and down-regulates the phosphorylation of ErbB2, ERK and AKT in tumors of MMTV-ErbB2/neu transgenic mice. These effects of Gemini BXL0124 in vivo were confirmed by using the ErbB2 overexpressing tumor cells derived from the mammary tumors of MMTV-ErbB2/neu mice. In conclusion, the Gemini vitamin D analog BXL0124 inhibits the growth of ErbB2 overexpressing mammary tumors through regulating the ErbB2/AKT/ERK signaling pathways, suggesting that Gemini vitamin D analog may be considered for translational studies. PMID- 20304053 TI - Expression of vitamin D receptor (VDR), cyclooxygenase-2 (COX-2) and 15 hydroxyprostaglandin dehydrogenase (15-PGDH) in benign and malignant ovarian tissue and 25-hydroxycholecalciferol (25(OH2)D3) and prostaglandin E2 (PGE2) serum level in ovarian cancer patients. AB - Ovarian carcinomas are associated with increased inflammation which is based upon an up-regulation of inducible cyclooxygenase-2 (COX-2). Moreover, based on our previous published data, the extra-renal vitamin D metabolism seems to be dysregulated in comparison to healthy tissue. In order to gain further insight into the prostaglandin (PG)- and vitamin D-metabolism in ovarian carcinomas, the study aimed to evaluate the expression of the PG metabolising enzymes COX-2 and 15-hydroxyprostaglandin dehydrogenase (15-PGDH) compared to the vitamin D receptor (VDR) in benign and malignant ovarian tissues. Additionally, we determined the 25-hydroxycholecalciferol (25(OH2)D3) serum levels. Expression of VDR, COX-2 and 15-PGDH was determined by Western blot analysis. Serum levels of 25(OH2)D3 and PGE2 were measured by chemiluminescence-based and colorimetric immunoassay. We detected significantly higher expressions of the PG metabolising enzymes 15-PGDH and COX-2 in malignant tissue and PGE2 serum levels were 2-fold higher in tumour patients. Furthermore, we found an inverse correlation to the VDR-expression which was 62.1% lower in malignant tissues compared to that in benign tissues. Surprisingly, we could not detect any differences between the 25(OH2)D3 serum levels in either group (n=20). These data suggest a correlation between PG- and vitamin D-metabolism in ovarian carcinomas. PMID- 20304054 TI - Developmental vitamin D3 deficiency induces alterations in immune organ morphology and function in adult offspring. AB - Vitamin D3 deficiency and insufficiency are common in women of child-bearing age. This may be cause for concern because vitamin D3 is a well known regulator of immune function and epidemiological evidence has suggested that immune disorders, including autoimmune diseases, could have developmental origins. However, it is not known whether a developmental deficiency in vitamin D3 could lead to persistent changes in the immune system in adult offspring. Given the prominence of receptors for vitamin D3 within immune cells we hypothesised that the developmental absence of vitamin D3 may alter thymic development and thus produce associated functional changes in T cells. We have developed a model of developmental vitamin D3 (DVD) deficiency in Sprague-Dawley rats, in which the vitamin D3 deficiency is transient and restricted to gestation. First we demonstrate that DVD deficiency induced an increase in central but not peripheral immune organ size. Second when stimulated, lymphocytes from DVD-deficient rats exhibit a pro-inflammatory phenotype. This is the first study to show that a transient vitamin D3 deficiency restricted to gestation can persistently alter aspects of immune phenotype and function in the adult offspring. Given an increased incidence of vitamin D3 deficiency in women of child-bearing age these findings may be highly relevant for autoimmune disorders with a developmental basis. PMID- 20304055 TI - The metabolism of 25-(OH)vitamin D3 by osteoclasts and their precursors regulates the differentiation of osteoclasts. AB - Current evidence suggests that levels of 25-(OH)vitamin D3 (25D), rather than 1alpha,25-(OH)2vitamin D3 (1,25D), directly affect bone mineralization and that the skeleton is a site of extra-renal synthesis of 1,25D. Since cells of the monocyte lineage can also metabolise 25D, it is possible that osteoclasts participate in local production of, and the response to, 1,25D. In this study, we investigated the effects of vitamin D metabolism on osteoclastogenesis using both the murine RAW 264.7 cell line and the human peripheral blood mononuclear cell (PBMC) models. PBMC-derived osteoclasts expressed cytoplasmic cyp27b1 and nuclear vdr proteins. PBMC expressed CYP27B1 mRNA, levels of which increased during RANKL induced differentiation into osteoclasts in both cell types. While 1,25D elicited a robust CYP24 transcriptional response in PBMC, the response to 25D was approximately 100-fold less at the concentrations used. Using media devoid of pre existing vitamin D metabolites, we found that 25D was metabolised by RAW 264.7 cells to 1,25D and resulted in significant elevation in the numbers of TRAP positive, multinucleated osteoclasts when present in the cultures for the first 3 5 days. These results suggest that vitamin D metabolism by osteoclast lineage cells is an important regulator of osteoclast formation. PMID- 20304056 TI - Epigenetic regulation of vitamin D converting enzymes. AB - While 25-OH-D3 serum levels in humans undergo a large seasonal variation, 1,25 (OH)2-D3 is regulated within a narrow range. We speculate that in addition to the known genomic and nongenomic regulation there could be further epigenetic mechanisms involved. We annotated the human CYP27B1 (alpha-1-hydroxylase) and CYP24A1 (24-hydroxylase) genes for CpG islands and sequenced these in bisulfite treated DNA extracted of peripheral blood lymphocytes from 384 individuals. 40 CpG sites could be analyzed, of these 15 in CYP27B1 and 25 in CYP24A1. The average methylation ratio (MR) in CYP27B1 was 11% (s.d. 5%) with the highest ratio observed in exon 1 (38%). CYP24A1 showed only a 6.5% MR (s.d. 5%). Neither CYP24A1 nor CYP27B1 MR correlated with season of examination date nor with current 25-OH-D3 and 1,25-(OH)2-D3 serum levels except of a weak association of three consecutive CYP27B1 CpG sites and 25-OH-D3 levels. In summary, human PBLs showed only weak methylation in the upstream region of CYP27B1 and none in CYP24A1. As PBLs represent an heterogeneous pool of cells, a further analysis of the seasonal methylation pattern in B or T cell subsets (or other tissues like liver or kidney) is warranted including an extended coverage of the CYP27B1 promotor. PMID- 20304057 TI - Interaction between vitamin D receptor with caveolin-3 and regulation by 1,25 dihydroxyvitamin D3 in adult rat cardiomyocytes. AB - We show that 1alpha,25-dihydroxyvitamin D3 (1,25(OH)2D3) and a synthetic non genotropic vitamin D analog agonist, 1a,25(OH)2-lumisterol (JN), exhibit similar rapid effects on sarcomere shortening (contraction) of isolated adult cardiomyocyte. We also report that the vitamin D receptor (VDR) specifically interacts with caveolin-3 in the t-tubules and sarcolemma of isolated adult rat cardiac myocytes. Confocal immunofluorescence microscopy analysis showed co localization of VDR and caveolin-3 in the t-tubules and sarcolemma of cardiomyocytes. Co-immunoprecipitation studies using VDR antibodies revealed that caveolin-3 specifically co-precipitates with the VDR and similarly the VDR is co precipitated with caveolin-3 antibody. VDR is also in association with Serca-2, the sarcoplasmic reticulum Ca2+-ATPase, as demonstrated by co immunoprecipitation, suggesting a role of VDR in regulating cardiac contractility by direct interaction with Serca-2. Treatment of isolated adult rat cardiomyocytes with 10 nM 1,25(OH)2D3 for 1 h caused decreased association between VDR and caveolin-3. These discoveries of the association between VDR and caveolin-3 and the regulation of this interaction by 1,25(OH)2D3 are fundamentally important in understanding 1,25(OH)2D3 signal transduction in heart cells and suggest a novel mechanism for VDR in the regulation of heart structure and function. PMID- 20304058 TI - Synthesis and preliminary biological evaluation of 20-epi-eldecalcitol [20-epi 1alpha,25-dihydroxy-2beta-(3-hydroxypropoxy)vitamin D3: 20-epi-ED-71]. AB - Eldecalcitol [1alpha,25-dihydroxy-2beta-(3-hydroxypropoxy)vitamin D3, developing code: ED-71] is an analog of active vitamin D3, 1alpha,25-dihydroxyvitamin D3 [1,25(OH)2D3] that possesses a hydroxypropoxy substituent at the 2beta-position of 1,25(OH)2D3. Eldecalcitol has potent biological effects on bone and is now in preparation for approval as a promising medicine for the treatment of osteoporosis in Japan. To explore chemical structure-biological activity relationships between eldecalcitol and related analogs, we have already synthesized 1-epi-eldecalcitol, 3-epi-eldecalcitol, and 1,3-diepi-eldecalcitol with inherent biological interests of each targeted analog and evaluated their biological responses. It has been reported that 20-epi-1,25(OH)2D3, a diastereomer of 1,25(OH)2D3 that possesses an inverted methyl substituent at the 20-position of the side chain, shows remarkably enhanced biological activities compared to parental compound, 1,25(OH)2D3. As a continuation of our modification studies on eldecalcitol, we took great interest in 20-epi-eldecalcitol and its biological responses. In this paper, the synthesis of 20-epi-eldecalcitol by the Trost coupling reaction between the A-ring fragment and the C/D-ring fragment as well as in vitro preliminary biological evaluation of 20-epi-eldecalcitol are described. In the induction of human myeloid leukemia cell (HL-60) differentiation, inhibition of the human histiocytic lymphoma cell (U937) proliferation, and increase in osteocalcin concentration in the human osteosarcoma cell (MG-63), 20-epi-eldecalcitol showed significantly enhanced activity compared to eldecalcitol. PMID- 20304060 TI - WITHDRAWN: Epigenetic modifications involved in the opposing regulation of CYP27B1 expression by the vitamin D receptor and parathyroid hormone. AB - This article has been withdrawn at the request of the author(s) and/or editor. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at http://www.elsevier.com/locate/withdrawalpolicy. PMID- 20304059 TI - Epigenetic silencing of CYP24 in the tumor microenvironment. AB - Calcitriol (1,25 dihydroxycholecalciferol) has significant anti-tumor activity in vitro and in vivo in a number of tumor model systems. We developed a system for isolation of fresh endothelial cells from tumors and Matrigel environments which demonstrate that CYP24, the catabolic enzyme involved in vitamin D signaling, is epigenetically silenced selectively in tumor-derived endothelial cells (TDEC). TDEC maintain phenotypic characteristics which are distinct from endothelial cells isolated from normal tissues and from Matrigel plugs (MDEC). In TDEC, calcitriol induces G(0)/G(1) arrest, modulates p27 and p21, and induces apoptotic cell death and decreases P-Erk and P-Akt. In contrast, endothelial cells isolated from normal tissues and MDEC are unresponsive to calcitriol-mediated anti proliferative effects despite intact signaling through the vitamin D receptor (VDR). In TDEC, which are sensitive to calcitriol, the CYP24 promoter is hypermethylated in two CpG island regions located at the 5'end; this hypermethylation may contribute to gene silencing of CYP24. The extent of methylation in these two regions is significantly less in MDEC. Lastly, treatment of TDEC with a DNA methyltransferase inhibitor restores calcitriol-mediated induction of CYP24 and resistance to calcitriol. These data suggest that epigenetic silencing of CYP24 modulates cellular responses to calcitriol. PMID- 20304061 TI - Vitamin D and diabetes. AB - On the basis of evidence from animal and human studies, vitamin D has emerged as a potential risk modifier for type 1 and type 2 diabetes (type 1 diabetes and type 2 diabetes). Vitamin D is thought to have both direct (through activation of the vitamin D receptor) and indirect (via regulation of calcium homeostasis) effects on various mechanisms related to the pathophysiology of both types of diabetes, including pancreatic beta-cell dysfunction, impaired insulin action and systemic inflammation. Observational case-control studies have shown that vitamin D supplementation in pregnancy or early childhood is associated with reduced risk of incident type 1 diabetes. There are no trials on the effect of vitamin D (ergocalciferol or cholecalciferol) on type 1 diabetes. An association between vitamin D insufficiency and incident type 2 diabetes has been reported in longitudinal observational studies, but the association is not consistent. Results from small underpowered trials and post-hoc analyses of data from larger trials designed for bone-specific outcomes show no effect of vitamin D supplementation on glycemia in healthy adults but vitamin D may retard the progression to diabetes in adults with glucose intolerance. Because vitamin D is an excellent marker of general health status, the positive results reported in some observational studies might reflect unmeasured and unaccounted confounding. Therefore, the hypothesis that vitamin D may modify diabetes risk needs to be confirmed in trials specifically designed for that purpose. PMID- 20304062 TI - A novel nonsecosteroidal VDR agonist (CH5036249) exhibits efficacy in a spontaneous benign prostatic hyperplasia beagle model. AB - To date, there have been no reports showing the efficacy of nonsecosteroidal vitamin D receptor (VDR) agonists in a benign prostatic hyperplasia (BPH) animal model. To examine the efficacy of CH5036249, a novel nonsecosteroidal VDR agonist, we orally administered the compound at 0.03 microg/kg to a beagle model with spontaneous BPH. Prostate volume was checked by rectal ultrasonic probe periodically during 11 months of administration and the prostate tissues histologically examined. CH5036249 inhibited prostate growth in two out of three dogs compared with vehicle-treated dogs. In the prostate specimens, substantial atrophy of the epithelium was observed in all dogs administered CH5036249. At the dose given, serum calcium levels slightly increased in the CH5036249-treated dogs but stayed within a normal range. We next examined the cell growth inhibition of CH5036249 using human prostate stromal cells and found the cell growth inhibitory activity of CH5036249 to be comparable to that of 1alpha,25(OH)2D3. The bioavailability from oral administration in rats was 95.1% with a t1/2 of 17.6 h. Both micro-AMES and micronucleus tests were negative. Although the results are still preliminary, we consider the novel nonsecosteroidal VDR agonist CH5036249 to be a possible new drug candidate for the treatment of BPH in humans. PMID- 20304063 TI - Involvement of ganglionic cholinergic receptors on the steroidogenesis in the luteal phase in rat. AB - The ovarian nervous plexus (ONP) is one of the principal extrinsic innervation pathways reaching the ovary from the superior mesenteric ganglion (SMG). The aims of this work were: (a) to determine if acetylcholine (Ach) in the SMG modifies the release of steroids and ovarian nitrites in an ex vivo SMG-ONP-ovary system on dioestrus (D) I and II, and (b) to demonstrate if the activities and gene expression of the steroidogenic enzymes 3beta-hydroxysteroid dehydrogenase (3beta HSD) and 20alpha-hydroxysteroid dehydrogenase (20alpha-HSD) are modified by cholinergic stimulus. The system was incubated in Krebs-Ringer buffer bicarbonate at 37 degrees C in metabolic bath. Ach (10(-6)M) was used as cholinergic agonist. Ach in SMG increased progesterone release at all the incubation times on DI and DII (*p<0.001). Androstenedione increased at 15 and 30min on DI, and at 30min on DII whereas nitric oxide (NO) increased at 30min on DI, and at 15 and 30min on DII. The activity of 3beta-HSD increased whereas the activity of 20alpha-HSD decreased (*p<0.001) on DI and DII. The gene expression of 3beta-HSD showed a significant increase at 120min on DI and DII ((o)p<0.01) and 20alpha-HSD diminished only on DII. The results show the importance of the SMG via the ovarian nervous plexus on the regulation of the steroid secretory activity and on the ovarian release of NO in the luteal phase. The complex synaptic connections in the prevertebral ganglia and the sympathetic ganglionic chain participate in the neuroendocrinological mechanisms that take place during the luteal steroidogenesis. PMID- 20304064 TI - Increased migratory properties of aortal smooth muscle cells exposed to calcitriol in culture. AB - The aim of the present study was to examine the effect of 1,25(OH)2D3 (calcitriol) on SMC (smooth muscle cell) migration, especially in the context to atherogenesis. SMCs were obtained from the aortas of newborn Wistar rats by enzymatic digestion. Different aspects of cell behavior during migration in culture were examined by phase contrast, fluorescence and electron microscopy (TEM, SEM) and supported by flow cytometric and biochemical analyses. Morphological studies revealed that supra-physiological (1-100 nmol/l) concentrations of calcitriol inhibit SMC differentiation, therefore these cells display several hallmarks of the synthetic state. Dynamic changes in actin cytoskeleton organization were a critical event in SMC shape, adhesion and spreading. Calcitriol diminished stress fibers assembly and focal adhesions formation. Reduced expression of beta1-integrin receptors on SMC surface after exposition to calcitriol coincided with increased proliferative and migratory activities of these cells. Moreover, after calcitriol stimulation, the ability of SMCs to the production of proinflamatory cytokines IFN-gamma, TNF-alpha and IL-6 was inhibited. The results from these comparative investigations indicate that 1,25(OH)2D3 inhibit differentiation and facilitate SMC migration in culture. It has been also suggested that such responses of SMCs to calcitriol play a beneficial role in fibrous cap formation during atherosclerotic process. PMID- 20304065 TI - Subtypes of immunoglobulin (Ig)-G antibodies against donor class II HLA and cross match results in three kidney transplant candidates. AB - Preexisting donor-specific antibodies (DSA) play a critical role in the success of solid-organ transplantation. Cross-match (CM) between donor lymphocytes and recipient serum is a pivotal methodology for detecting these antibodies. Luminex platform based solid-phase methodology for anti-human leukocyte antigen (HLA) antibody analysis has revolutionized the approach to antibody detection and HLA specificity identification. In this study, we have reported three cases of successful living donor kidney transplantations performed against strongly positive B lymphocyte flow cytometry (FC) CM owing to highly reactive DSA directed to HLA class II. IgG solid-phase subtype analysis showed that more than 50% of these antibodies were represented by non-complement binding IgG2/IgG4 subtypes. These findings account for antibody mediated rejection (AMR) free long term post-transplant course in these patients despite, the high level of DSA. Thus, we conclude that routine application of single HLA-coated beads (SAB) IgG subtype assay may provide new insights regarding transplantation or desensitization of patients presenting with negative B-cell complement dependent cytotoxic (CDC) and positive FC CM. PMID- 20304066 TI - Progression of dopaminergic depletion in a model of MPTP-induced Parkinsonism in non-human primates. An (18)F-DOPA and (11)C-DTBZ PET study. AB - Dopaminergic depletion in the nigrostriatal system is the neurochemical hallmark of Parkinson's disease (PD). Although numerous efforts have been made to determine the evolution of dopaminergic depletion in PD, "in vivo" data concerning the stages of this process are still scarce. We evaluated 6-[18F] fluoro-l-DOPA ((18)F-DOPA) and 11C-(+)-alpha-dihydrotetrabenazine ((11)C-DTBZ) using PET in a model of chronically MPTP-induced parkinsonism in non-human primates. METHODS: Sixty-seven cynomolgus monkeys (Macacafascicularis) were included in the study. Progressive parkinsonism was induced by repeated administration of small doses of MPTP (iv) over several months. Animals were classified as controls, asymptomatic, recovered (having exhibited parkinsonian features transiently) and stable parkinsonian, according to their motor status. Analysis of striatal dopaminergic activity was conducted by regions of interest (ROI) and statistical parametric mapping (SPM) over normalized parametric images. RESULTS: A progressive loss of striatal uptake was evident among groups for both radiotracers, which correlated significantly with the clinical motor status. Changes occurred earlier, i.e. in the less affected stages, with (11)C-DTBZ. Similar results were achieved by ROI and SPM analysis. Uptake was similar with both radiotracers for the asymptomatic and recovered groups. CONCLUSIONS: Serial assessment with (18)F-DOPA and (11)C-DTBZ PETs provides an effective approach to evaluate evolution of dopaminergic depletion in monkeys with MPTP-induced parkinsonism. This approach could be useful to perform studies aiming to test the effect of early therapeutic intervention and putative neuroprotective treatments. PMID- 20304067 TI - Neurodevelopmental disorders involving genomic imprinting at human chromosome 15q11-q13. AB - Human chromosome 15q11-q13 is subject to regulation by genomic imprinting, an epigenetic process by which genes are expressed in a parent-of-origin specific manner. Three neurodevelopmental disorders, Prader-Willi syndrome, Angelman syndrome, and 15q duplication syndrome, result from aberrant expression of imprinted genes in this region. Here, we review the current literature pertaining to mouse models and recently identified patients with atypical deletions, which shed light on the epigenetic regulation of the chromosome 15q11-q13 subregion and the genes that are responsible for the phenotypic outcomes of these disorders. PMID- 20304068 TI - Disruption of the epigenetic code: an emerging mechanism in mental retardation. AB - Mental retardation (MR) is a highly diverse group of cognitive disorders. Gene defects account for about half of all patients and mutations causative for impaired cognition have been identified in more than 400 genes. While there are numerous genetic defects underlying MR, a more limited number of pathways is emerging whose disruption appears to be shared by groups of MR genes. One of these common pathways is composed of MR genes that encode regulators of chromatin structure and of chromatin-mediated transcription regulation. Already more than 20 "epigenetic MR genes" have been identified and this number is likely to increase in the coming years when deep sequencing of exomes and genomes will become commonplace. Prominent examples of epigenetic MR genes include the methyl CpG-binding protein MECP2 and the CREB binding protein, CBP. Interestingly, several epigenetic MR proteins have been found to interact directly with one another or act together in complexes that regulate the local chromatin structure at target genes. Thus, it appears that the functions of individual epigenetic MR proteins converge onto similar biological processes that are crucial to neuronal processes. The next challenge will be to gain more insight into patterns of altered DNA methylation and histone modifications that are caused by epigenetic gene mutations and how these will disrupt the brain-specific expression of target genes. Such research may reveal that a wide variety of mutations in the genetic code result in a more limited number of disruptions to the epigenetic code. If so, this will provide a rationale for therapeutic strategies. PMID- 20304069 TI - Increase of GABAA receptor-mediated tonic inhibition in dentate granule cells after traumatic brain injury. AB - Traumatic brain injury (TBI) can result in altered inhibitory neurotransmission, hippocampal dysfunction, and cognitive impairments. GABAergic spontaneous and miniature inhibitory postsynaptic currents (sIPSCs and mIPSCs) and tonic (extrasynaptic) whole cell currents were recorded in control rat hippocampal dentate granule cells (DGCs) and at 90days after controlled cortical impact (CCI). At 34 degrees C, in CCI DGCs, sIPSC frequency and amplitude were unchanged, whereas mIPSC frequency was decreased (3.10+/-0.84Hz, n=16, and 2.44+/ 0.67Hz, n=7, p<0.05). At 23 degrees C, 300nM diazepam increased peak amplitude of mIPSCs in control and CCI DGCs, but the increase was 20% higher in control (26.81+/-2.2pA and 42.60+/-1.22pA, n=9, p=0.031) compared to CCI DGCs (33.46+/ 2.98pA and 46.13+/-1.09pA, n=10, p=0.047). At 34 degrees C, diazepam did not prolong decay time constants (6.59+/-0.12ms and 6.62+/-0.98ms, n=9, p=0.12), the latter suggesting that CCI resulted in benzodiazepine-insensitive pharmacology in synaptic GABA(A) receptors (GABA(A)Rs). In CCI DGCs, peak amplitude of mIPSCs was inhibited by 100microM furosemide (51.30+/-0.80pA at baseline and 43.50+/-5.30pA after furosemide, n=5, p<0.001), a noncompetitive antagonist of GABA(A)Rs with an enhanced affinity to alpha4 subunit-containing receptors. Potentiation of tonic current by the GABA(A)R delta subunit-preferring competitive agonist THIP (1 and 3microM) was increased in CCI DGCs (47% and 198%) compared to control DGCs (13% and 162%), suggesting the presence of larger tonic current in CCI DGCs; THIP (1microM) had no effect on mIPSCs. Taken together, these results demonstrate alterations in synaptic and extrasynaptic GABA(A)Rs in DGCs following CCI. PMID- 20304070 TI - Mechanisms underlying the losartan treatment-induced improvement in the endothelial dysfunction seen in mesenteric arteries from type 2 diabetic rats. AB - It is well known that type 2 diabetes mellitus is frequently associated with vascular dysfunction and an elevated systemic blood pressure, yet the underlying mechanisms are not completely understood. We previously reported that in mesenteric arteries from established type 2 diabetic Otsuka Long-Evans Tokushima fatty (OLETF) rats, which exhibit endothelial dysfunction, there is an imbalance between endothelium-derived vasodilators [namely, nitric oxide (NO) and hyperpolarizing factor (EDHF)] and vasoconstrictors [contracting factors (EDCFs) such as cyclooxygenase (COX)-derived prostanoids]. Here, we investigated whether the angiotensin II receptor antagonist losartan might improve endothelial dysfunction in OLETF rats at the established stage of diabetes. In mesenteric arteries isolated from OLETF rats [vs. those from age-matched control Long-Evans Tokushima Otsuka (LETO) rats]: (1) the acetylcholine (ACh)-induced relaxation was impaired, (2) the NO- and EDHF-mediated relaxations were reduced, (3) the ACh induced EDCF-mediated contraction and the production of prostanoids were increased, and (4) superoxide generation was increased. After such OLETF rats had received losartan (25 mg/kg/day p.o. for 4 weeks), their isolated mesenteric arteries exhibited: (1) improvements in ACh-induced NO- and EDHF-mediated relaxations, (2) reduced EDCF- and arachidonic acid-induced contractions, (3) suppressed production of prostanoids, (4) reduced PGE(2)-mediated contraction, and (5) reduced superoxide generation. Within the timescale studied here, losartan did not change the protein expressions of endothelial NO synthase, COX1, or COX2 in mesenteric arteries from either OLETF or LETO rats. Losartan thus normalizes vascular dysfunction in this type 2 diabetic model, and the above effects may contribute to the reduction of adverse cardiovascular events seen in diabetic patients treated with angiotensin II receptor blockers. PMID- 20304072 TI - DNA methylation profiling using the methylated-CpG island recovery assay (MIRA). AB - The methylated-CpG island recovery assay (MIRA) exploits the intrinsic specificity and the high affinity of a methylated-CpG-binding protein complex (MBD2B and MBD3L1) to methylated CpG dinucleotides in genomic DNA. The MIRA approach works on double-stranded DNA and does not depend on the application of methylation-sensitive restriction enzymes. It can be performed on a few hundred nanograms of genomic DNA. Recently, the MIRA technique has been used to profile DNA methylation patterns at a resolution of 100 base pairs along the entire genome of normal human B-lymphocytes. The MIRA method is compatible with microarray and next generation DNA sequencing approaches. We describe the principles and details of this method applied for methylation profiling of genomes containing methylated CpG sequences. PMID- 20304071 TI - The expression of ELK transcription factors in adult DRG: Novel isoforms, antisense transcripts and upregulation by nerve damage. AB - ELK transcription factors are known to be expressed in a number of regions in the nervous system. We show by RT-PCR that the previously described Elk1, Elk3/Elk3b/Elk3c and Elk4 mRNAs are expressed in adult dorsal root ganglia (DRG), together with the novel alternatively spliced isoforms Elk1b, Elk3d and Elk4c/Elk4d/Elk4e. These isoforms are also expressed in brain, heart, kidney and testis. In contrast to Elk3 protein, the novel Elk3d isoform is cytoplasmic, fails to bind ETS binding sites and yet can activate transcription by an indirect mechanism. The Elk3 and Elk4 genes are overlapped by co-expressed Pctk2 (Cdk17) and Mfsd4 genes, respectively, with the potential formation of Elk3/Pctaire2 and Elk4/Mfsd4 sense-antisense mRNA heteroduplexes. After peripheral nerve injury the Elk3 mRNA isoforms are each upregulated approximately 2.3-fold in DRG (P<0.005), whereas the natural antisense Pctaire2 isoforms show only a small increase (21%, P<0.01) and Elk1 and Elk4 mRNAs are unchanged. PMID- 20304073 TI - Control of translational initiation in the wheat-embryo cell-free protein expression system for producing homogenous products. AB - Wheat-embryo cell-free protein expression system allows efficient production of a wide variety of proteins. Homogeneity of the end products is an important characteristic of an advanced cell-free system that will be used in a field of protein science such as structural biology. A translation enhancer such as the omega sequence derived from tobacco mosaic virus, that allows cap-independent translation of the mRNA in the cell-free system, is required for low-cost preparation of template mRNAs in the cell-free translation system. However, the use of translational enhancers often leads to unexpected byproducts. Several AUU codons in the omega sequence can potentially function as translation initiators. We confirmed that the in-frame AUU in the omega sequence functions as a non canonical start codon and results in the extension of the N-terminus of the target protein in some cases. Investigation of the selectivity of non-canonical initiation codon under the control of omega sequence in the wheat-embryo cell free system revealed that seven non-AUG codons, CUG, AUA, AUU, GUG, ACG, AUC, and UUG, are recognized as translation initiators. We found that the introduction of an in-frame stop codon just upstream of the target open reading frame is an efficient way to avoid unexpected byproducts. This minor but effective modification facilitates production of homogeneous proteins within the wheat embryo cell-free protein expression system at the preparative scale. PMID- 20304074 TI - Anatomical phenotyping in a mouse model of fragile X syndrome with magnetic resonance imaging. AB - Fragile X Syndrome (FXS) is the most common single gene cause of inherited mental impairment, and cognitive deficits can range from simple learning disabilities to mental retardation. Human FXS is caused by a loss of the Fragile X Mental Retardation Protein (FMRP). The fragile X knockout (FX KO) mouse also shows a loss of FMRP, as well as many of the physical and behavioural characteristics of human FXS. This work aims to characterize the anatomical changes between the FX KO and a corresponding wild type mouse. Significant volume decreases were found in two regions within the deep cerebellar nuclei, namely the nucleus interpositus and the fastigial nucleus, which may be caused by a loss of neurons as indicated by histological analysis. Well-known links between these nuclei and previously established behavioural and physical characteristics of FXS are discussed. The loss of FMRP has a significant effect on these two nuclei, and future studies of FXS should evaluate the biochemical, physiological, and behavioral consequences of alterations in these key nuclei. PMID- 20304075 TI - Propofol allows precise quantitative arterial spin labelling functional magnetic resonance imaging in the rat. AB - Functional magnetic resonance imaging (fMRI) techniques highlight cerebral vascular responses which are coupled to changes in neural activation. However, two major difficulties arise when employing these techniques in animal studies. First is the disturbance of cerebral blood flow due to anaesthesia and second is the difficulty of precise reproducible quantitative measurements. These difficulties were surmounted in the current study by using propofol and quantitative arterial spin labelling (QASL) to measure relative cerebral blood volume of labelled water (rCBV(lw),) mean transit time (MTT) and capillary transit time (CTT). The ASL method was applied to measure the haemodynamic response in the primary somatosensory cortex following forepaw stimulation in the rat. Following stimulation an increase in signal intensity and rCBV(lw) was recorded, this was accompanied by a significant decrease in MTT (1.97+/-0.06s to 1.44+/-0.04s) and CTT (1.76+/-0.06s to 1.39+/-0.07s). Two animals were scanned repeatedly on two different experimental days. Stimulation in the first animal was applied to the same forepaw during the initial and repeat scan. In the second animal stimulation was applied to different forepaws on the first and second days. The control and activated ASL signal intensities, rCBVlw on both days were almost identical in both animals. The basal MTT and CTT during the second scan were also very similar to the values obtained during the first scan. The MTT recorded from the animal that underwent stimulation to the same paw during both scanning sessions was very similar on the first and second days. In conclusion, propofol induces little physiological disturbance and holds potential for longitudinal QASL fMRI studies. PMID- 20304077 TI - An expanded phylogeny of treefrogs (Hylidae) based on nuclear and mitochondrial sequence data. AB - The treefrogs (Hylidae) make up one of the most species-rich families of amphibians. With 885 species currently described, they contain >13% of all amphibian species. In recent years, there has been considerable progress in resolving hylid phylogeny. However, the most comprehensive phylogeny to date (Wiens et al., 2006) included only 292 species, was based only on parsimony, provided only poor support for most higher-level relationships, and conflicted with previous hypotheses in several parts (including the monophyly and relationships of major clades of Hylinae). Here, we present an expanded phylogeny for hylid frogs, including data for 362 hylid taxa for up to 11 genes (4 mitochondrial, 7 nuclear), including 70 additional taxa and >270 sequences not included in the previously most comprehensive analysis. The new tree from maximum likelihood analysis is more well-resolved, strongly supported, and concordant with previous hypotheses, and provides a framework for future systematic, biogeographic, ecological, and evolutionary studies. PMID- 20304076 TI - Identifying robust and sensitive frequency bands for interrogating neural oscillations. AB - Recent years have seen an explosion of interest in using neural oscillations to characterize the mechanisms supporting cognition and emotion. Oftentimes, oscillatory activity is indexed by mean power density in predefined frequency bands. Some investigators use broad bands originally defined by prominent surface features of the spectrum. Others rely on narrower bands originally defined by spectral factor analysis (SFA). Presently, the robustness and sensitivity of these competing band definitions remains unclear. Here, a Monte Carlo-based SFA strategy was used to decompose the tonic ("resting" or "spontaneous") electroencephalogram (EEG) into five bands: delta (1-5Hz), alpha-low (6-9Hz), alpha-high (10-11Hz), beta (12-19Hz), and gamma (>21Hz). This pattern was consistent across SFA methods, artifact correction/rejection procedures, scalp regions, and samples. Subsequent analyses revealed that SFA failed to deliver enhanced sensitivity; narrow alpha sub-bands proved no more sensitive than the classical broadband to individual differences in temperament or mean differences in task-induced activation. Other analyses suggested that residual ocular and muscular artifact was the dominant source of activity during quiescence in the delta and gamma bands. This was observed following threshold-based artifact rejection or independent component analysis (ICA)-based artifact correction, indicating that such procedures do not necessarily confer adequate protection. Collectively, these findings highlight the limitations of several commonly used EEG procedures and underscore the necessity of routinely performing exploratory data analyses, particularly data visualization, prior to hypothesis testing. They also suggest the potential benefits of using techniques other than SFA for interrogating high-dimensional EEG datasets in the frequency or time-frequency (event-related spectral perturbation, event-related synchronization/desynchronization) domains. PMID- 20304079 TI - Effect of apple intake on fecal microbiota and metabolites in humans. AB - The effects of apple intake on the fecal flora, water content, pH, and metabolic activities in eight healthy volunteers and the utilization of apple pectin in vitro were investigated. Although several isolates of Bifidobacterium, Lactobacillus, Enterococcus, and the Bacteroides fragilis group utilized apple pectin, most isolates of Escherichia coli, Collinsela aerofaciense, Eubacterium limosum, and Clostridium perfringens could not. When fecal samples from healthy adults were incubated in liquid broth with apple pectin present or absent, the numbers of Bifidobacterium and Lactobacillus in the former were higher than those in the later. After the intake of apples (2 apples a day for 2 weeks) by eight healthy adult humans, the number of bifidobacteria in feces increased (p < 0.05 on day 7 and p < 0.01 on day 14 of the intake period), and the numbers of Lactobacillus and Streptococcus including Enterococcus tended to increase. However, lecithinase-positive clostridia, including C. perfringens, decreased (p < 0.05), and Enterobacteriaceae and Pseudomonas tended to decrease. Moreover, the concentrations of fecal acetic acid tended to increase on apple intake. The fecal ammonia concentration showed a tendency to reduce and fecal sulfide decreased (p < 0.05) on apple intake. These findings indicate that apple consumption is related to an improved intestinal environment, and apple pectin is one of the effective apple components improving the fecal environment. PMID- 20304078 TI - Interactions between declarative and procedural-learning categorization systems. AB - Two experiments tested whether declarative and procedural memory systems operate independently or inhibit each other during perceptual categorization. Both experiments used a hybrid category-learning task in which perfect accuracy could be achieved if a declarative strategy is used on some trials and a procedural strategy is used on others. In the two experiments, only 2 of 53 participants learned a strategy of this type. In Experiment 1, most participants appeared to use simple explicit rules, even though control participants reliably learned the procedural component of the hybrid task. In Experiment 2, participants pre trained either with the declarative or procedural component and then transferred to the hybrid categories. Despite this extra training, no participants in either group learned to categorize the hybrid stimuli with a strategy of the optimal type. These results are inconsistent with the most prominent single- and multiple system accounts of category learning. They also cannot be explained by knowledge partitioning, or by the hypothesis that the failure to learn was due to high switch costs. Instead, these results support the hypothesis that declarative and procedural memory systems interact during category learning. PMID- 20304080 TI - An indirect ELISA for serodiagnosis of cattle footrot caused by Fusobacterium necrophorum. AB - A serodiagnostic ELISA (rL-ELISA) using recombinant truncated leukotoxin protein PL2 (aa 311-644) of Fusobacterium necrophorum as antigen was developed for detection of antibodies against F. necrophorum from cattle footrot. In rL-ELISA, the recombinant diagnostic antigen showed no cross-reaction with antisera against bovine foot and mouth disease virus, bovine rhinotracheitis virus, bovine viral diarrhea virus, bovine rotavirus type A, bovine Escherichia coli, and bovine Salmonella. The rL-ELISA could confirm the existence of antibodies against F. necrophorum at day 7 after infection. Detection of the field samples indicated relative sensitivity of rL-ELISA to nL-ELISA using the purified native leukotoxin A as antigen was 96.43%, and relative specificity of rL-ELISA to nL-ELISA was 94.26%. These data demonstrated the rL-ELISA would have a potential use for early diagnosis of cattle footrot caused by F. necrophorum. PMID- 20304081 TI - Screening lactic acid bacteria from swine origins for multistrain probiotics based on in vitro functional properties. AB - Lactic acid bacteria originated from swine feces and intestines were selected for potential probiotics based on their bile-salt resistance, low pH tolerance, potential adhesion to epithelial cells and especially functional properties, including production of antimicrobial substances, bile-salt hydrolase (BSH) and amylolytic activity. Results showed 7 isolates with antimicrobial activity, 5 with BSH activity and 3 with amylolytic activity were preliminarily selected from 485 lactic acid bacteria based on their highest potential with functional properties in vitro. The 15 isolates were further assayed on the essential characteristics as potential probiotics. All isolates were fully tolerant to 0.3% bile salts and 11 of them were able to resist pH 3 for 3 h without loss of viable cells. The eleven isolates were then evaluated on their adhesion capability. Wide variation in the hydrophobic character and specific adhesion efficiency was observed and three isolates G1-1, G22-2 and G8-5, with respective antimicrobial, BSH and amylolytic activities were finally selected. In addition, the three isolates were compatible in the coexistence assay. Isolate G1-1 was identified as Lactobacillus salivarius by API system and a 16S rRNA gene sequence analysis. Both G8-5 and G22-2 showed the closest homology to Lactobacillus reuteri according to their 16S rRNA gene sequences (99%). From the study, the three Lactobacilli strains were shown to share the functional properties necessary for probiotics use in animal additives. Their compatibility with respective in vitro activities was expected to show enhanced in vivo efficacy after combination for multistrain probiotics use. PMID- 20304082 TI - Detection and control of a nosocomial respiratory syncytial virus outbreak in a stem cell transplantation unit: the role of palivizumab. AB - Respiratory syncytial virus (RSV) is a common community-acquired virus that causes upper and lower respiratory tract infections in children, hematologic malignancy patients, and hematopoietic stem cell transplant (HSCT) recipients. Nosocomial transmission of RSV in immunocompromised patients can significantly affect morbidity, mortality, and duration of hospitalization. Stringent infection control measurements are needed to control further hospital transmission. Prophylactic palivizumab was found to result in a significant reduction in hospitalization rates in high-risk children. In this article, we report a nosocomial outbreak of RSV in an adult HSCT unit (4 pods) from January 16 to February 4, 2004, including the infection control interventions used and the prophylactic administration of palivizumab in high-risk patients. Active surveillance identified 5 cases, a substantial increase from previous seasons (2 or 3 cases per season). All infected patients were isolated to 1 nursing pod and placed on contact isolation. All patients on the HSCT unit underwent rapid RSV antigen screening using nasal washes; this was repeated 1 week later, and 1 additional RSV case was identified. Patients identified to be at increased risk for RSV infection received prophylactic palivizumab. Routine screenings of the staff and visitors were undertaken. All patient and visitor areas were thoroughly cleaned with bleach. We educated health care workers about RSV transmission, highlighting proper hand hygiene and contact precautions. Four of 6 patients with RSV infection developed RSV pneumonia, and 2 of these patients died. Staff and visitors with upper respiratory symptoms were screened, and all were negative for RSV. Prophylactic palivizumab was administered in 16 patients who tested negative for RSV, but were considered to be at increased risk for RSV infection. None of these patients developed RSV infections. An RSV outbreak was controlled using prompt preventive measures, including cohorting patients, with a dedicated health care staff; contact isolation of patients; strict adherence to hand hygiene; and screening of visitors, family members, and health care staff for upper respiratory infection symptoms. Immunoprophylaxis with palivizumab, administered to high-risk patients, complemented strict infection control intervention. Thus, the role of palivizumab in the control of RSV hospital outbreaks merits further investigation. PMID- 20304083 TI - Cyclosporine dose intensity and risk of acute graft-versus-host disease: trough versus area under the curve. PMID- 20304084 TI - Hematopoietic stem cell transplantation for multiple sclerosis: collaboration of the CIBMTR and EBMT to facilitate international clinical studies. AB - Clinical investigation of autologous hematopoietic stem cell transplantation (HSCT) as therapy for multiple sclerosis (MS) has been ongoing for over a decade. While several phase II studies have been finalized or are in progress, no definitive prospective randomized studies comparing HSCT versus alternative therapies for MS have been completed. In this conference report of North American and European experts who are involved in the care of MS patients, including neurologists and HSCT physicians, and representatives of the Center for International Blood and Marrow Transplant Research (CIBMTR) and European Group for Blood and Marrow Transplantation (EBMT), we (1) critically review progress to date in HSCT for MS; (2) describe current registry based projects including long term follow-up studies in HSCT for MS and harmonization of the MS disease specific research forms that will be used in future by both databases; (3) discuss challenges in study design for a prospective randomized clinical trial of HSCT versus alternative therapy for MS such as feasibility, and the importance of multidisciplinary clinical teams, need for a large sample size and duration of observation required for outcomes assessment; and (4) address future directions in HSCT therapy for MS. To undertake a definitive multicenter clinical trial in autologous HSCT for MS, it will be important to begin well in advance to assemble the team, evaluate proposals for study design, and consider options for the infrastructure and logistical support that will be needed. International collaboration, including partnership with the CIBMTR and EBMT, may be desirable and may in fact be critical for successful completion of a definitive comparative study. PMID- 20304085 TI - A preclinical model of double- versus single-unit unrelated cord blood transplantation. AB - Cord blood transplantation (CBT) with units containing total nucleated cell (TNC) dose >2.5 x 10(7)/kg is associated with improved engraftment and decreased transplant-related mortality. For many adults no single cord blood units are available that meet the cell dose requirements. We developed a dog model of CBT to evaluate approaches to overcome the problem of low cell dose cord blood units. This study primarily compared double- versus single-unit CBT. Unrelated dogs were bred and cord blood units were harvested. We identified unrelated recipients that were dog leukocyte antigen (DLA)-88 (class I) and DLA-DRB1 (class II) allele matched with cryopreserved units. Each unit contained or=10 mm) colorectal polyps at CTC. METHODS: We reviewed results from 5124 consecutive adults (mean age, 56.9 y; 2792 women) who received CTC screening at 1 institution over a 52-month period. All nondiminutive lesions confirmed at subsequent colonoscopy were grouped by size and histology features. Rates of cancer and high grade dysplasia were calculated for various sizes. Adenomas were classified as advanced if they were 10 mm or greater and/or contained high-grade dysplasia or a prominent villous component. RESULTS: A total of 755 polyps 6 mm or greater were identified during colonoscopy examinations in 479 patients. The rate of malignancy, according to polyp size, was 0% (0 of 464) for polyps 6 to 9 mm, 0.9% (2 of 216) for polyps 10 to 19 mm, 6.1% (2 of 33) for polyps 20 to 29 mm, and 38.1% (16 of 42) for polyps 30 mm or greater. High-grade dysplasia was observed in 0.4% (2 of 464) of 6- to 9-mm polyps and 7.9% (23 of 291) of lesions 10 mm or greater. A prominent villous component was seen in 3.4% (16 of 464) of 6- to 9-mm polyps. The overall rate of advanced histology in small polyps was 3.9% (18 of 464). CONCLUSIONS: Small (6-9 mm) polyps rarely contained high-grade dysplasia (0.4%); none was malignant. The malignancy rate for large (1-2 cm) colorectal polyps was less than 1%. These findings indicate the potential for less aggressive management of lesions detected by CTC. PMID- 20304098 TI - Paris criteria are effective in diagnosis of primary biliary cirrhosis and autoimmune hepatitis overlap syndrome. AB - BACKGROUND & AIMS: Primary biliary cirrhosis (PBC) and autoimmune hepatitis (AIH) differ in clinical, laboratory, and histologic features as well as in response to therapy. A small subgroup of patients have an overlap syndrome with features of both diseases, although there is no consensus on its definition or diagnostic criteria. We evaluated the significance of the criteria used to diagnose PBC-AIH overlap syndrome. METHODS: This retrospective, single-center study included all patients diagnosed with PBC, AIH, or PBC-AIH overlap syndrome, based on the Paris criteria, since January 1990 (n = 134); patients were followed up for 9.7 +/- 3.7 years. The 3 groups were compared for their clinical, laboratory, and histologic features. Patients with overlap syndrome or PBC were graded by the revised and simplified AIH scoring systems to assess the ability of this system to identify AIH cases properly. RESULTS: The sensitivity and specificity of the Paris criteria for diagnosing the overlap syndrome were 92% and 97%, respectively. The sensitivity and specificity of the AIH scoring systems were considerably lower. Among patients with the overlap syndrome, the 10-year, transplantation-free survival rate was 92%. CONCLUSIONS: The Paris diagnostic criteria detect overlap syndrome (PBC and AIH) with high levels of sensitivity and specificity. The clinical value of the revised and simplified AIH scoring system is not as reliable. Patients with PBC-AIH overlap syndrome have a 92% rate of 10-year, transplantation-free survival. PMID- 20304099 TI - Level of hepatitis B virus DNA in inactive carriers with persistently normal levels of alanine aminotransferase. AB - BACKGROUND & AIMS: Little is known about the level of hepatitis B virus (HBV) DNA in individuals with chronic, inactive HBV infections. Patients who test positive for the antibody to hepatitis B e antigen (anti-HBe) and have normal levels of alanine aminotransferase for more than 10 years have a low risk of HBV reactivation and are considered to be inactive carriers. We investigated HBV DNA levels in inactive carriers and identified factors that correlated with this state among anti-HBe-positive carriers with HBV DNA levels of 10(4) copies/mL or greater (5.26 copies/mL = 1 IU/mL). METHODS: HBV DNA levels were assayed in 250 inactive carriers with persistently normal alanine aminotransferase levels for more than 10 years. Clinical and virologic features were compared between inactive carriers (with HBV DNA levels > or =10(4) copies/mL) and age-matched patients with HBe antigen-negative chronic hepatitis (controls, n = 90). RESULTS: The median level of HBV DNA among inactive carriers was 3.70 log(10) copies/mL (range, undetectable to 5.98 log(10) copies/mL). Ninety (36%) had levels of 10(4) copies/mL or greater. Compared with control patients, significant differences of inactive carriers included sex (more female patients), lower HBV DNA levels, and lower prevalence of genotype C virus and the basal core promoter mutation T1762/A1764. The prevalence of the precore mutation A1896 was similar between groups. Multiple logistic regression analyses identified male sex, HBV DNA levels greater than 10(5) copies/mL, and the basal core promoter mutation as independent factors that correlated with active disease. CONCLUSIONS: Nearly 40% of inactive carriers had HBV DNA levels of 10(4) copies/mL or greater. Female sex, HBV DNA levels of 10(4) to 10(5) copies/mL, and wild-type basal core promoter correlated with inactive carrier state. PMID- 20304100 TI - Descending inhibitory pain modulation is impaired in patients with chronic pancreatitis. AB - BACKGROUND & AIMS: Pain is a prominent symptom in chronic pancreatitis (CP), but the underlying mechanisms are incompletely understood. We investigated the role of descending pain modulation from supraspinal structures as well as central nervous system sensitization in patients with pain from CP. METHODS: Twenty-five patients with CP and 15 healthy volunteers were included. Descending pain modulation was investigated by diffuse noxious inhibitory control (a descending inhibitory response after conditioning stimulation). Central pain processing was investigated as the perceptual responses to multimodal (electrical, thermal, and mechanical) stimulations of the rectosigmoid and evoked brain potentials after electrical stimulation of the rectosigmoid. RESULTS: Compared with healthy volunteers, the efficacy of diffuse noxious inhibitory control was reduced in patients with CP (13% +/- 21% vs 39% +/- 22%, respectively; F = 3.8; P = .01); central sensitization was indicated by remote hyperalgesia in the rectosigmoid to electrical stimulation (21 +/- 15 mA vs 27 +/- 15 mA; F = 6.2; P = .02) and heat stimulation (51 degrees C +/- 5 degrees C vs 53 degrees C +/- 4 degrees C; F = 5.9; P = .02). Compared with controls, patients with CP had increased latency of the early P1 peak to rectosigmoid stimulation (85 +/- 21 ms vs 108 +/- 28 ms, respectively; P = .02), possibly reflecting reorganization of central pain pathways. CONCLUSIONS: Patients with CP have impairments in inhibitory pain modulation and evidence of central sensitization. Treatment of their pain therefore should focus not only on the pancreas, but also on descending pain modulation from supraspinal structures and central nervous system sensitization. PMID- 20304101 TI - Health-related quality of life in patients with hepatocellular carcinoma: a systematic review. AB - BACKGROUND & AIMS: This systematic review was conducted to identify the following: (1) generic and disease-specific measures used to assess health related quality of life (HRQOL) in patients with hepatocellular carcinoma (HCC); (2) HRQOL in patients with HCC compared with those with chronic liver disease and the general population; (3) effects of treatment (liver surgery, hepatic artery transcatheter treatment, and radiotherapy) on HRQOL; (4) relationships between physical variables, symptoms, and HRQOL; (5) relationships between demographic characteristics, psychological variables, and HRQOL; and (6) effects of psychological interventions on HRQOL. METHODS: Computerized databases including British Nursing Index, Cumulative Index to Nursing and Allied Health Literature, Cochrane library, PsychoINFO, and Pubmed were searched. RESULTS: Thirty-six articles were identified. The results suggested the following. Four original articles described the development of standardized measures to assess liver cancer-specific HRQOL. Patients with HCC reported worse physical, emotional, and functional HRQOL, but better social/family HRQOL compared with the general population. HRQOL improved after liver surgery, hepatic artery transcatheter treatment, and radiotherapy. Better liver function, early stage of disease, and no recurrence were correlated positively with better HRQOL; and pain, fatigue, nausea, and performance status were associated with worse HRQOL. HRQOL was correlated negatively with depression, uncertainty, chance health locus of control, and positively with satisfaction with medical services. Psychosocial interventions may reduce negative feelings and enhance HRQOL. CONCLUSIONS: Future work should explore the effects of psychological variables on HRQOL and the interaction between physical and psychological variables in relation to HRQOL. PMID- 20304102 TI - Functional dyspepsia impacts absenteeism and direct and indirect costs. AB - BACKGROUND & AIMS: Functional dyspepsia (FD) is a common morbid condition but data are limited on the direct and indirect costs for employees with FD or on its impact on productivity. Few data on absenteeism and no objective information are available. This study aimed to assess the impact of FD on costs and effects on absenteeism and work output (productivity). METHODS: We performed a retrospective analysis of payroll data and adjudicated health insurance medical and prescription claims collected over a 4-year study period (January 1, 2001 to December 31, 2004) from more than 300,000 employees. Data from employees with and without (controls) FD were compared using 2-part regression techniques. Outcome measures included medical (total and by place of service) and prescription costs, absenteeism, and objectively measured productivity output. RESULTS: Employees with FD (N = 1669) had greater average annual medical and prescription drug costs and indirect costs (owing to sick leave and short- and long-term disability absences) than controls (N = 274,206). Compared with controls, the FD employees incurred costs that were $5138 greater and had greater costs for each place of service (all P < .0001). The employees with FD had an additional 0.83 absence days per year and produced 12% fewer units per hour than controls (both P < .05). CONCLUSIONS: Employees with FD have greater costs at all places of service and lower productivity than employees without FD. PMID- 20304103 TI - Does hepatitis C virus really form quasispecies? PMID- 20304104 TI - Effect of 5-aminosalicylate on allergic rhinitis model in mice. AB - Previous studies have shown that peroxisome proliferator-activated receptor gamma (PPARgamma) is involved in allergic rhinitis. It has been reported that 5 aminosalicylate (5-ASA) has an affinity for PPARgamma, but the effects of 5-ASA on the nasal symptoms of allergic rhinitis are unclear. This study aimed to clarify the effects of 5-ASA on nasal symptoms in an allergic rhinitis model in mice. Female BALB/c mice were sensitized by intraperitoneal injection of ovalbumin (OVA) and aluminium hydroxide hydrate gel (alum) on days 0, 5, 14 and 21. Seven days later, mice were sensitized by the intranasal application of OVA thrice a week. 5-ASA was also administered orally after instillation of the antigen from day 28. The severity of allergic rhinitis was assessed by determining the extent of 2 nasal allergic symptoms-sneezing and nasal rubbing. In addition, serum OVA-specific immunoglobulin E (IgE) antibody, interleukin (IL) 4, and IL-10 levels in nasal lavage fluid and histamine sensitivity were determined. Repeated oral administration of 5-ASA attenuated the progression of nasal symptoms in sensitized mice in a dose-dependent manner. Additionally, 5-ASA prevented an increase in histamine sensitivity. Finally, 5-ASA inhibited both OVA specific IgE antibody and IL-4 production; however, it had no effect on IL-10 levels. These results indicate that 5-ASA has a prophylactic effect on allergic rhinitis. PMID- 20304105 TI - Natural isoprenoids inhibit LPS-induced-production of cytokines and nitric oxide in aminobisphosphonate-treated monocytes. AB - The inhibition of mevalonate pathway through genetic defects (mevalonate kinase deficiency, MKD) or pharmacologic drugs (aminobisphosphonates) causes a shortage of intermediate compounds and, in particular, of geranylgeranyl-pyrophosphate (GGPP) associated to the activation of caspase-1 and IL-1beta release. Geraniol (GOH), farnesol (FOH), geranylgeraniol (GGOH) and menthol (MOH), due to their isoprenoid structure, are supposed to enter the mevalonate pathway and to by-pass the biochemical block, reconstituting the pathway. Considering the already known side effects of aminobisphosphonates, and the lack of a specific treatment for MKD, we evaluated the impact of these natural isoprenoids compounds in a RAW cell lines chemically treated with the aminobisphosphonate alendronate, and in monocytes isolated from 2 patients affected by MKD. GOH, FOH, GGOH and MOH were all capable to diminish inflammatory marker levels induced by LPS. These natural isoprenoids could be proposed as novel therapeutic approach for the still orphan drug MKD, but also considered for the evaluation of possible inflammatory side effects of aminobisphosphonates. PMID- 20304106 TI - WITHDRAWN: Transdermal potential and anti-inflammatory effects of nanocurcumin from nanogel systems. AB - This article has been withdrawn at the request of the author(s) and/or editor. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at http://www.elsevier.com/locate/withdrawalpolicy. PMID- 20304107 TI - Restricted domain mobility in the Candida albicans Ess1 prolyl isomerase. AB - Ess1 is a peptidyl prolyl cis/trans isomerase that is required for virulence of the pathogenic fungi Candida albicans and Cryptococcus neoformans. The enzyme isomerizes the phospho-Ser-Pro linkages in the C-terminal domain of RNA polymerase II. Its human homolog, Pin1, has been implicated in a wide range of human diseases, including cancer and Alzheimer's disease. Crystallographic and NMR studies have demonstrated that the sequence linking the catalytic isomerase domain and the substrate binding WW domain of Pin1 is unstructured and that the two domains are only loosely associated in the absence of the substrate. In contrast, the crystal structure of C. albicans Ess1 revealed a highly ordered linker that contains a three turn alpha-helix and extensive association between the two tightly juxtaposed domains. In part to address the concern that the marked differences in the domain interactions for the human and fungal structures might reflect crystal lattice effects, NMR chemical shift analysis and 15N relaxation measurements have been employed to confirm that the linker of the fungal protein is highly ordered in solution. With the exception of two loops within the active site of the isomerase domain, the local backbone geometry observed in the crystal structure appears to be well preserved throughout the protein chain. The marked differences in interdomain interactions and linker flexibility between the human and fungal enzymes provide a structural basis for therapeutic targeting of the fungal enzymes. PMID- 20304108 TI - A solution NMR investigation into the murine amelogenin splice-variant LRAP (Leucine-Rich Amelogenin Protein). AB - Amelogenins are the dominant proteins present in ameloblasts during the early stages of enamel biomineralization, making up >90% of the matrix protein. Along with the full-length protein there are several splice-variant isoforms of amelogenin present including LRAP (Leucine-Rich Amelogenin Protein), a protein that consists of the first 33 and the last 26 residues of full-length amelogenin. Using solution-state NMR spectroscopy we have assigned the (1)H-(15)N HSQC spectrum of murine LRAP (rp(H)LRAP) in 2% acetic acid at pH 3.0 by making extensive use of previous chemical shift assignments for full-length murine amelogenin (rp(H)M180). This correlation was possible because LRAP, like the full length protein, is intrinsically disordered under these solution conditions. The major difference between the (1)H-(15)N HSQC spectra of rp(H)M180 and rp(H)LRAP was an additional set of amide resonances for each of the seven non-proline residues between S12 and Y12 near the N-terminus of rp(H)LRAP indicating that the N-terminal region of LRAP exists in two different conformations. Analysis of the proline carbon chemical shifts suggests that the molecular basis for the two states is not a cis-trans isomerization of one or more of the proline residues in the N-terminal region. Starting from 2% acetic acid, where rp(H)LRAP was monomeric in solution, NaCl addition effected residue specific changes in molecular dynamics manifested by the reduction in intensity and disappearance of (1)H-(15)N HSQC cross peaks. As observed for the full-length protein, these perturbations may signal early events governing supramolecular self-assembly of rp(H)LRAP into nanospheres. However, the different patterns of (1)H-(15)N HSQC cross peak perturbation between rp(H)LRAP and rp(H)M180 in high salt suggest that the termini may behave differently in their respective nanospheres, and perhaps, these differences contribute to the cell signaling properties attributable to LRAP but not to the full-length protein. PMID- 20304109 TI - Sustained plasmid DNA release from dissolving mineral coatings. AB - Calcium phosphate (CaP) minerals such as hydroxyapatite are able to bind a diverse range of biological molecules due to the presence of anions and cations in their crystal structure. The well-characterized ability of CaP minerals to bind and release plasmid DNA, coupled with the ability of biodegradable CaP coatings to form on the surface of common biomaterials, provides a potential mechanism for controlled release of plasmid DNA from various biomaterials. In this study we hypothesized that the release of plasmid DNA from CaP coatings formed on poly(lactide-co-glycolide) (PLG) substrates would be dependent on both the intrinsic properties of the CaP mineral coating and the surrounding solution conditions. Experiments were designed to consider two general parameters: (i) the stability of various CaP mineral coatings in solution environments that are relevant to physiological conditions; (ii) the relationship between mineral stability and sustained plasmid DNA release. Our results corroborate previous studies that have demonstrated a direct relationship between intrinsic mineral composition and mineral stability. In addition, we further demonstrate that ion composition and pH of the surrounding solution environment can significantly influence mineral stability. In turn, mineral stability significantly influenced release of plasmid DNA from mineral coatings in vitro, and the DNA release efficiency could be tuned by controlling the mineral properties in various solution environments. These CaP mineral coatings may be a useful platform for plasmid DNA delivery applications using various biomaterial platforms. PMID- 20304110 TI - Biomimetic remineralization as a progressive dehydration mechanism of collagen matrices--implications in the aging of resin-dentin bonds. AB - Biomineralization is a dehydration process in which water from the intrafibrillar compartments of collagen fibrils are progressively replaced by apatites. As water is an important element that induces a lack of durability of resin-dentin bonds, this study has examined the use of a biomimetic remineralization strategy as a progressive dehydration mechanism to preserve joint integrity and maintain adhesive strength after ageing. Human dentin surfaces were bonded with dentin adhesives, restored with resin composites and sectioned into sticks containing the adhesive joint. Experimental specimens were aged in a biomimetic analog containing remineralizing medium and control specimens in simulated body fluid for up to 12 months. Specimens retrieved after the designated periods were examined by transmission electron microscopy for the presence of water-rich regions using a silver tracer and for collagen degradation within the adhesive joints. Tensile testing was performed to determine the potential loss of bond integrity after ageing. Control specimens exhibited severe collagen degradation within the adhesive joint after ageing. Remineralized specimens exhibited progressive dehydration, as manifested by silver tracer reduction and partial remineralization of water-filled microchannels within the adhesive joint, as well as intrafibrillar remineralization of collagen fibrils that were demineralized initially as part of the bonding procedure. Biomimetic remineralization as a progressive dehydration mechanism of water-rich, resin-sparse collagen matrices enables these adhesive joints to resist degradation over a 12-month ageing period, as verified by the conservation of their tensile bond strength. The ability of the proof of concept biomimetic remineralization strategy to prevent bond degradation warrants further development of clinically relevant delivery systems. PMID- 20304111 TI - Nanostructured poly(epsilon-caprolactone)-silica xerogel fibrous membrane for guided bone regeneration. AB - A novel fibrous membrane was developed for guided bone regeneration (GBR) through electrospinning a uniform poly(epsilon-caprolactone) (PCL)-silica hybrid sol. The membrane was composed of fibers with a mean diameter of approximately 400 nm. The hybrid fibers were nano-sized with uniform patterns throughout the fibers, in contrast to the homogeneous structure of pure PCL fibers. The tensile strengths and elastic moduli of the membranes were significantly enhanced with increasing silica content up to 40%. The surfaces of the hybrid membranes were highly hydrophilic with a water contact angle of almost zero. The hybrid membranes possessed excellent in vitro cellular responses in terms of proliferation and differentiation of pre-osteoblast cells. The in vivo animal tests not only confirmed excellent biocompatibility but also revealed bioresorbability of the membranes. These mechanical and biomedical properties make the hybrid membranes very attractive as GBR applications. PMID- 20304112 TI - Evaluation of laparoscopic sleeve gastrectomy on weight loss and co-morbidity. AB - BACKGROUND: The sleeve gastrectomy is a surgical technique to treat morbid obesity by both restrictive and probably hormonal action. Originally developed as a first stage to gastric bypass, it is more and more performed as a sole procedure. Therefore it is important to report results on weight loss and reduction in co-morbidity. METHODS: A consecutive series of 74 morbid obese patients were evaluated. Parameters were operative variables, complications, weight loss and the need for medication for co-morbidity at least six months postoperatively. RESULTS: Six procedures included the removal of a band and twice a vertical banded gastroplasty was performed previously. Median operating time diminished over time to 71 min. Three procedures were converted into open approach. Major complications were rhabdomyolysis (2), bleeding (2) and leakage (4). Four days was the mean hospital stay. The median follow-up was 12 months (range 6-33). The median percentage of excess weight loss was 49.6% (range 22 96%EWL). The median loss in BMI points was 23.1% (range 9-50%BMIL). Three quarters of the patients were able to diminish or stop their medication for diabetes, hypertension and hyperlipedemia. CONCLUSION: The laparoscopic gastric sleeve is effective in reduction of both weight and co-morbidity and has potential as a sole procedure. Patient's selection is, however, recommendable for initial surgical experience and longer follow-up will be necessary. PMID- 20304127 TI - Absidia corymbifera endocarditis: survival after treatment of disseminated mucormycosis with radical resection of tricuspid valve and right ventricular free wall. PMID- 20304128 TI - Ascending aortitis and aortic valve endocarditis in an infant. PMID- 20304129 TI - An unusual tumor of the esophagus. PMID- 20304130 TI - The seventh edition of the American Joint Committee on Cancer/International Union Against Cancer Staging Manuals: the new era of data-driven revisions. PMID- 20304131 TI - Live surgery should not be outlawed at national and regional cardiothoracic meetings. PMID- 20304132 TI - A cancer staging primer: lung. PMID- 20304133 TI - The Cardiothoracic Surgery Network: randomized clinical trials in the operating room. PMID- 20304134 TI - Where does atrial fibrillation surgery fail? Implications for increasing effectiveness of ablation. AB - OBJECTIVE: Surgical ablation of atrial fibrillation is generally safe and effective, but atrial fibrillation redevelops in approximately 20% of patients. We sought to determine anatomic factors, technology factors, or both that contribute to these failures. METHODS: Four hundred eight patients underwent 5 types of atrial fibrillation ablation depending on their atrial fibrillation history and need for concomitant surgical intervention: the classic maze procedure, high-intensity focused ultrasound, the left atrial maze procedure, the biatrial maze procedure, and pulmonary vein isolation. Ninety-five percent of patients with preoperative atrial fibrillation underwent surgical ablation. RESULTS: Patients undergoing high-intensity focused ultrasound had a high rate of late postoperative percutaneous ablation (37.5%) after surgical intervention (P < .001 vs the other groups). At last follow-up, freedom from atrial fibrillation and need for ablation was as follows: classic maze procedure, 90%; high-intensity focused ultrasound, 43%; left atrial maze procedure, 79%; biatrial maze procedure, 79%; and pulmonary vein isolation, 69% (P < .001 between groups). For those with atrial fibrillation, mapping and ablation were performed in 23.6% (n = 27), and all patients with high-intensity focused ultrasound had failure of the box lesion around the pulmonary veins. Of those with just the left atrial maze procedure or pulmonary vein isolation, the right atrium was the source for failure in 75% (6/8). CONCLUSIONS: Patients undergoing high-intensity focused ultrasound had a high need for postoperative ablation and low freedom from atrial fibrillation. The classic maze procedure had the best results. Left atrial ablation might allow failure from right atrial foci. Matching the technology and lesion set to the patient yields good results and can be applied in 95% of patients. We suggest others obtain late catheter ablation to correct remaining atrial fibrillation, and add to the paucity of late data regarding failure mode. PMID- 20304136 TI - Moderate chronic kidney disease and left ventricular hypertrophy after aortic valve replacement for aortic valve stenosis. AB - OBJECTIVE: Left ventricular hypertrophy regression is assumed to be one of the most important goals after aortic valve replacement for aortic stenosis. A moderate decrease in the glomerular filtration rate is associated with a significantly increased risk of left ventricular hypertrophy in hypertensive patients. The effect of moderate kidney disease on left ventricular hypertrophic remodeling in other conditions of chronic left ventricular pressure overload, such as aortic stenosis, remains unknown. Therefore we tested the hypothesis that moderate chronic kidney disease affects left ventricular mass regression in patients undergoing isolated aortic valve replacement for aortic stenosis. METHODS: In 157 patients with aortic stenosis, left ventricular mass regression was assessed at 18 months after aortic valve replacement. Among them, 73 (46%) had a moderate chronic kidney disease (glomerular filtration rate between 60 and 30 mL/min per 1.73 m(2)). Patients with severely impaired kidney function (glomerular filtration rate of <30 mL/min per 1.73 m(2)) were excluded. RESULTS: After surgical intervention, left ventricular mass was significantly lower from baseline value in both groups, but patients with moderate chronic kidney disease continued to show an increased left ventricular mass (61 +/- 18 vs 50 +/- 16 g/m(2.7), P = .0001). The baseline glomerular filtration rate was significantly related to left ventricular mass at 18 months after surgical intervention (beta = -0.17, r(2) = 0.45, P = .01) and left ventricular mass absolute (beta = 0.18, r(2) = 0.19, P = .03) and relative (beta = 0.20, r(2) = 0.21, P = .02) regression. These associations persisted after adjusting for confounding factors, including hypertension and patient-prosthesis mismatch. After a mean time of 34 +/- 12 months from surgical intervention, congestive heart failure symptoms developed mainly in subjects with moderate chronic kidney disease (adjusted hazard ratio, 1.9; 95% confidence interval, 1.2-3.9; P = .035). CONCLUSIONS: Patients with aortic stenosis with concomitant moderate chronic kidney disease present a less evident left ventricular mass regression after aortic valve replacement. Moreover, this condition is related to an increased occurrence of congestive heart failure after surgical intervention. PMID- 20304137 TI - Aortic cusp extension valvuloplasty with or without tricuspidization in children and adolescents: long-term results and freedom from aortic valve replacement. AB - OBJECTIVE: Aortic cusp extension valvuloplasty is increasingly used in the management of children and adolescents with aortic stenosis or regurgitation. The durability of this approach and the freedom from valve replacement are not well defined. A study was undertaken to investigate outcomes. METHODS: From July 1987 to November 2008, 142 patients aged less than 19 years underwent aortic cusp extension valvuloplasty in the form of pericardial cusp extension and tricuspidization (when needed). Three patients with truncus arteriosus and severe truncal valve insufficiency were excluded. From the available follow-up data of 139 patients, 50 had bicuspid aortic valves, 40 had congenital aortic valve stenosis, 41 had combined congenital aortic valve stenosis/insufficiency, and 8 had other diagnoses. Median follow-up was 14.4 years (0.1-21.4). Long-term mortality and freedom from aortic valve replacement were studied. RESULTS: There were no early, intermediate, or late deaths. Z-values of left ventricular end diastolic dimension, aortic annulus, aortic sinus diameter, and sinotubular junction diameter before aortic valve replacement were 4.2 +/- 3.11, 2.3 +/- 1.25, 4.4 +/- 1.23, and 1.84 +/- 1.28, respectively. During the follow-up period, 64 patients underwent aortic valve reinterventions. The Ross procedure was performed in 32 of 139 patients (23%) undergoing aortic cusp extension valvuloplasty. Other aortic valve replacements were undertaken after 16 aortic cusp extension valvuloplasties (11.5%). Freedom from a second aortic cusp extension valvuloplasty or aortic valve replacement at 18 years was 82.1% +/- 4.2% and 60.0% +/- 7.2%, respectively. CONCLUSION: Aortic cusp extension valvuloplasty is a safe and effective surgical option with excellent survival and good long-term outcomes in children and adolescents. The procedure provides acceptable durability and satisfactory freedom from aortic valve replacement. PMID- 20304139 TI - Twenty-three years of single-stage end-to-side anastomosis repair of interrupted aortic arches. AB - OBJECTIVE: This study defined long-term results of a policy of single-stage repair of interrupted aortic arch with end-to-side anastomosis. METHODS: Records of 112 consecutive patients undergoing interrupted aortic arch repair between 1985 and 2007 were reviewed. Single-stage repair was performed in 95 patients, with 90 having end-to-side repair. RESULTS: There were 11 in-hospital deaths (10%). Twelve patients needed arch reintervention during the same hospital stay: 7 for residual arch obstruction and 5 for left main bronchus obstruction. Nine patients were unavailable for follow-up. After a mean of 10 +/- 7 years, 6 late deaths occurred, for 18-year survival of 92% (95% confidence interval [CI], 84% 97%). Patients with end-to-side anastomoses had better 18-year survival (97%, 95% CI, 87%-99%, vs 74%, 95% CI, 44%-89%, P < .01). After discharge, 19 patients underwent further aortic arch intervention. The only factors predictive of late arch reintervention were technique other than end-to-side (P < .001) and reoperation for left outflow tract obstruction. Freedom from arch reintervention after end-to-side repair was 78% at 18 years (95% CI, 59%-89%). Another 16 patients had significant residual obstruction. The 18-year freedom from hypertension was 88% (95% CI, 72%-95%). CONCLUSIONS: Single-stage repair with end to-side anastomosis seems the best approach for most neonates with interrupted aortic arch, because it provides relief of the arch obstruction with low early mortality. After 2 decades of experience with this approach, incidence of late hypertension seems minimal. The need for further arch reintervention warrants close follow-up of these patients. PMID- 20304141 TI - Esophagectomy after anti-reflux surgery. AB - OBJECTIVE: There are few data on whether prior fundoplication has an impact on subsequent esophageal resection and reconstruction. The aim of this study is to review our experience with patients undergoing esophagectomy after previous fundoplication. METHODS: Medical records were reviewed of all patients undergoing esophageal resection from 1988 to 2008 at the Mayo Clinic. Patients with a fundoplication before esophagectomy were compared with a matched control group who had esophagectomy alone. RESULTS: There were 2313 esophageal resections, and 80 patients had undergone at least 1 previous anti-reflux surgery. Indications for esophagectomy were benign stricture/perforation in 41 patients, cancer in 28 patients, and dysplasia in 11 patients. The surgical approach was Ivor Lewis in 38 patients, left thoracoabdominal in 29 patients, transhiatal in 10 patients, and McKeown in 3 patients. The conduit used was stomach in 70 patients, jejunum in 6 patients, and colon in 3 patients; 1 patient had a diversion and cervical esophagostomy only. Operative mortality occurred in 3 patients (3.7%). Postoperative complications occurred in 50 patients (62.5%), including anastomotic leak in 17 (21.5%). Sixteen patients (20%) required reoperation for complications. Complication, anastomotic leak, and reoperation rates were significantly higher in patients with anti-reflux surgery before esophagectomy compared with matched controls. CONCLUSION: Esophagectomy after prior anti-reflux surgery is challenging, but the stomach is usually a suitable conduit for esophageal replacement. Patients with a history of anti-reflux surgery who undergo esophagectomy are at significantly increased risk for postoperative complications, anastomotic leak, and need for reoperation. PMID- 20304144 TI - The impact of induction therapy on morbidity and operative mortality after resection of primary lung cancer. AB - OBJECTIVE: Use and operative results of neoadjuvant therapy before major elective resection for primary lung cancer were examined in the Society of Thoracic Surgeons General Thoracic Surgical Database. METHODS: Lobectomy and pneumonectomy for primary lung cancer were identified in 12,201 patients between January 2002 and June 2008. After excluding procedures for missing clinical staging or end points; institutions with more than 10% missing data for clinical stage, discharge mortality, or length of stay; and patients treated with chemotherapy or radiation for unrelated disease, there remained 5376 resections. Study end points were discharge mortality, length of stay more than 14 days, and major morbidity. Multivariate analysis using propensity scores stratified into quintiles measured the effect of induction therapy. RESULTS: In 525 of 5376 procedures (9.8%), chemotherapy (n = 153), radiotherapy (23), or chemoradiotherapy (349) preceded resection. Compared with resection only, patients receiving induction therapy were younger and had fewer comorbidities, more reoperative surgery, and higher rates of pneumonectomy. Clinical IIIA-N2 disease was treated with induction therapy in only 203 of 397 patients (51.1%). Propensity-adjusted rates detected no difference in discharge mortality, prolonged length of stay, or a composite of major morbidity for patients receiving induction therapy. Similar results were obtained in a logistic regression model (discharge mortality P = .9883; prolonged hospital stay P = .9710; major morbidity P = .9678). CONCLUSION: Less than 10% of all major lung resections for primary carcinoma and just more than half of all resections for clinical stage IIIA-N2 disease are preceded by neoadjuvant chemotherapy or radiation. This study does not support concerns over excessive operative risk of induction therapy. PMID- 20304142 TI - Differential matrix metalloproteinase levels in adenocarcinoma and squamous cell carcinoma of the lung. AB - OBJECTIVE: The matrix metalloproteinases (MMPs) have been implicated in the aggressive course of non-small cell lung cancer (NSCLC). However, there are a large number of MMP subtypes with diverse proteolytic substrates and different induction pathways. This study tested the hypothesis that a differential MMP profile would exist between NSCLC and normal lung and that MMP patterns would differ between NSCLC histologic types. METHODS: NSCLC samples and remote normal samples were obtained from patients with stage I or II NSCLC with either squamous cell (n = 22) or adenocarcinoma (n = 19) histologic characteristics. Absolute concentrations for each of the MMP subclasses were determined by a calibrated and validated multiplex suspension array: collagenases (MMP-1, -8, and -13), gelatinases (MMP-2 and -9), lysins (MMP-2 and -7), and elastase (MMP-12). RESULTS: Overall, MMP levels were significantly increased in NSCLC compared with normal. For example, MMP-1 and MMP-7 increased by approximately 10-fold in NSCLC (P < .05). Moreover, a different MMP portfolio was observed between NSCLC histologic types. For example MMP-1, -8, -9, and -12 increased by more than 4 fold in squamous cell versus adenocarcinoma (P < .05). In those patients who had recurrence within 3 years of resection, 3-fold higher levels of MMP-8 and -9 were observed (P < .05). CONCLUSION: Increased levels of a number of MMP types occur with NSCLC, but the MMP profile was distinctly different between histologic types and in those patients with recurrence. These different MMP profiles may be important in the mechanistic basis for the natural history of different NSCLC types, as well as identifying potential prognostic and therapeutic targets. PMID- 20304145 TI - Ventricular restraint therapy for heart failure: the right ventricle is different from the left ventricle. AB - OBJECTIVE: Effects of ventricular restraint on the left ventricle are well documented, but effects on the right ventricle are not. We hypothesized that restraint affects the right and left ventricles differently. METHODS: We studied acute effects of restraint on left and right ventricular mechanics in healthy sheep (n = 14) with our previously described technique of adjustable and measurable restraint. Transmural pressure, myocardial oxygen consumption indices, diastolic compliance, and end-systolic elastance were assessed at 4 restraint levels for both ventricles. We then studied long-term effects of restraint for 4 months in an ovine model of ischemic dilated cardiomyopathy (n = 6). Heart failure was induced by coronary artery ligation, and polypropylene mesh was wrapped around the heart to simulate clinical restraint therapy. All subjects were followed up with serial cardiac magnetic resonance imaging to assess left and right ventricular volumes and function. RESULTS: Restraint decreased left ventricular transmural pressure (P < .03) and myocardial oxygen consumption indices (P < .05) but not left ventricular diastolic compliance (P = .52). Restraint had no effect on right ventricular transmural pressure (P = .82) or myocardial oxygen consumption indices (P = .72) but reduced right ventricular diastolic compliance (P < .01). In long-term studies, restraint led to reverse left ventricular remodeling with decreased left ventricular end-diastolic volume (P < .006) but did not affect right ventricular end-diastolic volume (P = .82). CONCLUSIONS: Ventricular restraint affects the left and right ventricles differently. Benefits of restraint for right ventricular function are unclear. The left ventricle can tolerate more restraint than the right ventricle. With current devices, the right ventricle may limit overall therapeutic efficacy. PMID- 20304146 TI - Heat shock protein 27: induction by gastroduodenal reflux in vivo and augmentation of human esophageal mucosal cell growth in vitro. AB - OBJECTIVE: Acid exposure to esophageal epithelium leads to hyperplasia and mucosal thickening. This is associated with upregulation of antiapoptotic genes. Recently, heat shock proteins have been implicated in esophageal mucosal response to stress. We sought to determine the influence of gastroduodenal reflux on esophageal mucosal heat shock protein 27 gene (murine analog Hspb1, human HSPB1) expression in vivo and the effect of HSPB1 overexpression on proliferation of esophageal mucosal cells in vitro. METHODS: Balb/c mice underwent either anastomosis of gastroesophageal junction and first portion of duodenum to induce continuous gastroduodenal reflux (n = 14) or sham procedure (n = 12). Quantitative reverse transcriptase polymerase chain reaction was used to determine the influence of gastroduodenal reflux on Hspb1 expression. Immunofluorescent microscopy and immunoblotting were used to quantify changes in heat shock protein 27 protein expression. Lentiviral infection techniques were used to overexpress HSPB1 in human esophageal epithelial cells. Both 3-(4,5 dimethylthiazole-2-yl) 2,5,-diphenyl tetrazolium bromide and 5-bromo-2 deoxyuridine incorporation assays were used to assess cell proliferation. RESULTS: Expressions of Hspb1 and its protein product were increased in esophageal tissue after 12 weeks' reflux relative to sham control group. Expression was located mainly in hyperplastic epithelial cells. Overexpression of HSPB1 in human esophageal epithelial cells resulted in increased proliferation. CONCLUSIONS: Heat shock protein 27 is upregulated in response to gastroduodenal reflux and is a mediator of human esophageal epithelial cell proliferation and growth. This novel finding illustrates the importance of its expression in the development of inflammation and mucosal thickening associated with esophageal reflux. PMID- 20304147 TI - Prolonged donor heart preservation with pinacidil: the role of mitochondria and the mitochondrial adenosine triphosphate-sensitive potassium channel. AB - OBJECTIVE: Prolonged donor heart preservation is important in cardiovascular surgery. This study examined the effect of pinacidil, a nonselective adenosine triphosphate-sensitive potassium channel opener, on donor heart preservation when added to histidine tryptophan ketoglutarate solution and the role of mitochondria in this protection. METHODS: Sprague-Dawley rat hearts received one of 5 preservation solutions in the Langendorff perfusion apparatus (24 per group): (1) histidine tryptophan ketoglutarate solution; (2) histidine tryptophan ketoglutarate solution containing pinacidil; (3) histidine tryptophan ketoglutarate solution containing pinacidil and 5-hydroxydecanote, a mitochondrial adenosine triphosphate-sensitive potassium channel blocker; (4) histidine tryptophan ketoglutarate solution containing pinacidil and Hoechst Marion-Roussel 1098, a sarcolemmal adenosine triphosphate-sensitive potassium channel blocker; and (5) histidine tryptophan ketoglutarate solution containing pinacidil, 5-hydroxydecanote, and Hoechst-Marion-Roussel 1098. After a 10-minute equilibration period, all the hearts in the different preservation solutions were placed in cold storage for 8 hours, followed by 60 minutes of reperfusion. Hemodynamics, mitochondrial respiratory function, adenosine triphosphate level, cardiac troponin I release, and ultrastructure were examined. RESULTS: Histidine tryptophan ketoglutarate solution containing 0.5 mmol/L pinicidal significantly improved heart function, coronary flow, myocardial ultrastructure, and cardiac troponin I release after reperfusion (P < .01 or P < .05). In the pinacidil group at the end of storage and the end of reperfusion, mitochondrial respiratory function and myocardial adenosine triphosphate levels were superior when compared with other groups (P < .01 or P < .05). These beneficial effects of pinacidil were blocked by 100 mumol/L 5-hydroxydecanote. CONCLUSION: Histidine tryptophan ketoglutarate solution containing pinacidil provides better cardioprotection with preservation of mitochondrial energy. This effect of pinacidil appears to depend on both mitochondrial and sarcolemmal adenosine triphosphate sensitive potassium channel. PMID- 20304148 TI - Aortic decision making in Loeys-Dietz syndrome. PMID- 20304151 TI - Organ transplantation in numbers: Brazil reaches its goals. Preface. PMID- 20304152 TI - Survival on waiting list for liver transplantation before and after introduction of the model for end-stage liver disease score. AB - BACKGROUND: Since July 2006, the Model for End-stage Liver Disease (MELD) score has served as the national basis for allocation of donor livers for transplantation in Brazil. Patients with higher MELD scores receive greater priority for allocation regardless of the time on the waiting list. PURPOSE: To investigate the impact of MELD score implementation on the survival of waiting list patients. METHODS: A retrospective study of patients registered at the national Organ Procurement Organization (OPO) for the liver transplantation waiting list between January 2004 and June 2006 (pre-MELD) and between July 2006 and December 2008 (post-MELD). RESULTS: We included listed patients awaiting liver transplantation in the pre-MELD era (n = 250, 48.4%) and in the post-MELD era (n = 266, 51.6%). The times awaiting transplant prior to and after the MELD system were 487.2 +/- 384.8 days and 183.9 +/- 157.2 days, respectively. Prior to the MELD score, waiting list survivals were greater when compared to rates in the current system. Early posttransplant patient survival rates were significantly reduced in the post-MELD era (83.4%) compared to the period before MELD implementation (93.2%). CONCLUSIONS: MELD score provides a transparent, objective system to drive allocation policy; however, it presents several important limitations. Constant need of changes and reevaluation are needed as an evolutionary process. Future changes in the present system may be addressed by adjusting the MELD system. PMID- 20304153 TI - Survival before and after model for end-stage liver disease score introduction on the Brazilian liver transplant waiting list. AB - INTRODUCTION: To examine whether the official adoption of Model for End-Stage Liver Disease (MELD) as a criterion for organ allocation was effective, we studied risk factors for patient deaths and the accuracy of the MELD score to predict mortality. METHODS: Patients on the waiting list for liver transplantation were divided into two periods depending on whether they were on the waiting list before (period 1) or after (period 2) the MELD introduction in Brazil. The Kaplan-Meier method with log-rank tests were used to study patient survivals. Predictive factors were identified using the Cox regression method. A receiver operating characteristic (ROC) curve was used to analyze Child-Turcotte Pugh (CTP) and MELD accuracy. RESULTS: We analyzed 295 patients in period 1 and 240 in period 2. The survivals after 3, 6, 9, and 12 months in periods 1 and 2, were 95.6%, 90.5%, 84.9%, and 69.6% vs 95.7%, 92.1%, 85.3%, and 83.3%, respectively (P = NS). Multivariate analysis showed CTP, MELD-Na, and albumin levels, besides spontaneous bacterial peritonitis (SBP), to be independent factors related to survival in period 1. In period 2, CTP, creatinine levels, international normalized ratio, besides spontaneous bacterial peritonitis, were the independent factors. The ROC curve for CTP was 0.676 and for MELD, 0.644 (P = .4) in period 1. In period 2, the ROC curve for CTP was 0.680 and for MELD, 0.718 (P = .4). CONCLUSION: Patient survival on the waiting list for liver transplantation did not change at 1 year after the introduction of the MELD. PMID- 20304154 TI - Why not to use kidney grafts from elderly donors. AB - BACKGROUND: Kidney transplantation is widely recognized as the best treatment in patients who require renal replacement therapy. Although considered a clinical and surgical triumph, it is also a source of frustration because of lack of donor organs and the growth of waiting lists. Strategies need to be developed to increase the supply of organs. One measure is use of expanded criteria for donation. OBJECTIVE: To evaluate the effect of donor age on cadaver graft survival. MATERIALS AND METHODS: We reviewed the medical records for 454 patients who underwent kidney transplantation with cadaver donors from April 1987 to December 2003. RESULTS: Donor age had a significant effect on kidney transplant survival. Survival of grafts from donors aged 16 to 40 years (mean, 143.30 months) was significantly greater compared with that of grafts from donors older than 40 years (66.46 months) (P = .005). The HLA matching and cold ischemia time did not significantly affect transplant survival (P = .98 and P = .16, respectively). CONCLUSIONS: Kidneys from cadaver donors older than 40 years significantly compromised graft survival, generating a negative effect via early return of recipients to waiting lists and increasing the rate of repeat transplantation, risk of death, and unnecessary costs. PMID- 20304155 TI - Surgical complications in 100 donor hepatectomies for living donor liver transplantation in a single Brazilian center. AB - The rising demand for liver transplantation has continued to outspace the availability of deceased donor organs, leading to the need for other treatment options including living donor liver transplantation (LDLT). A precise evaluation of surgical complications is the most important issue in this setting. There are controversies about donor morbidity with reports ranging from 13%-75%. The aim of this study was to retrospectively analyze 100 LDLTs performed in a single Brazilian center from December 2002 to August 2008, stratifying the complications according to Clavien's scoring system. None of the donors experienced life threatening complications or died. The majority of donors (n = 74) did not suffer any complication. Twenty-eight complications were observed in 26 patients. Fifty seven hepatectomies were performed for adult and 43 for pediatric transplantations. According to the Brisbane classifications, we performed 49 right and 2 left hepatectomies as well as 49 left lateral segmentectomies. According to Clavien, the complications were as follows: grade I (n = 11; 39.2%); grade II (n = 8; 28.5%); and grade III (n = 9; 32.3%). No patient presented with grade IV or V. The most common problem a biliary tract injury, similar to other series. In this Brazilian series, hepatectomy for LDLT was a safe procedure with low morbidity, regardless of the type of liver resection. This practice will probably continue to grow to alleviate the pressure of growing waiting lists. PMID- 20304156 TI - Evaluation of living donor liver transplantation: causes for exclusion. AB - The decision to perform organ donation surgery involves a series of risks for the live donor including death. The aim of this study was to evaluate exclusion criteria for living donor liver transplantation, as well as to identify the rate of exclusion in each of the 3 process phases according to the Live Donor Evaluation Protocol for adult and child recipients. From December 2001 to December 2007, we evaluated 223 donors among whom 142 were excluded in various phases. The data were statistically evaluated. Among the 142 excluded donors, 113 (79.6%) had an adult recipient. The elimination rates for adult recipients were as follows: 68 cases in phase I, 41 cases in phase II, and 4 cases in phase III. Concerning child recipients, 29 (20.4%) donors were excluded: 17 in phase I, and 12 in phase II. Concerning adult recipients, sons and daughters were the largest part of the excluded donors, with withdrawal as the principal reason for exclusion followed by recipient death. Regarding child recipients the parents represented the largest number of excluded donors due to withdrawal followed by abnormal blood test results. Thus, 36.5% of potential donors were effective donors. PMID- 20304157 TI - Liver transplantation using University of Wisconsin or Celsior preserving solutions in the portal vein and Euro-Collins in the aorta. AB - INTRODUCTION: Orthotopic liver transplantation (OLT) is today the gold standard treatment of the end-stage liver disease. Different solutions are used for graft preservation. Our objective was to compare the results of cadaveric donor OLT, preserved with the University of Wisconsin (UW) or Celsior solutions in the portal vein and Euro-Collins in the aorta. METHODS: We evaluated retrospectively 72 OLT recipients, including 36 with UW solution (group UW) and 36 with Celsior (group CS). Donors were perfused in situ with 1000 mL UW or Celsior in the portal vein of and 3000 mL of Euro-Collins in the aortia and on the back table managed with 500 mL UW or Celsior in the portal vein, 250 mL in the hepatic artery, and 250 mL in the biliary duct. We evaluated the following variables: donor characteristics, recipient features, intraoperative details, reperfusion injury, and steatosis via a biopsy after reperfusion. We noted grafts with primary nonfunction (PNF), initial poor function (IPF), rejection episodes, biliary duct complications, hepatic artery complications, re-OLT, and recipient death in the first year after OLT. RESULTS: The average age was 33.6 years in the UW group versus 41 years in the CS group (P = .048). There was a longer duration of surgery in the UW group (P = .001). The other recipient characteristics, ischemia reperfusion injury, steatosis, PNF, IPF, rejection, re-OLT, and recipient survival were not different. Stenosis of the biliary duct occured in 3 (8.3%) cases in the UW group and 8 (22.2%) in the CS (P = .19) with hepatic artery thrombosis in 4 (11.1%) CS versus none in the UW group (P = .11). CONCLUSION: Cadaveric donor OLT showed similar results with organs preserved with UW or Celsior in the portal vein and Euro-Collins in the aorta. PMID- 20304158 TI - Analysis of the liver effluent as a marker of preservation injury and early graft performance. AB - In liver transplantation, the effluent solution, which represents the washout of residual preservation solution, can be collected before reperfusion to determine the release of the markers of endothelial cell injury and damage to the liver. The enzyme activities detected in the washout solution may allow the development of an index that could be clinically valuable for the prediction of early posttransplant graft function. In the present study, we collected liver effluents from 47 livers at the time of graft rinsing to measure liver enzymes (aminotransferases and lactate dehydrogenase) as well as the serum enzyme levels of the recipients for correlation with early postoperative graft viability (1 month survival). The patients were divided into two groups: death (D) and survival (S). Nonparametric statistical analysis was used with the level of significance set at P < .05. Aminotransferases and lactate dehydrogenase levels higher among the D group (P < .05 for all measurements), leading us to conclude that the effluent represents a good marker of preservation injury and early graft performance. PMID- 20304159 TI - Ex vivo lung perfusion: early report of Brazilian experience. AB - INTRODUCTION: Only about 15% of the potential candidates for lung donation are considered suitable for transplantation. A new method for ex vivo lung perfusion (EVLP) can be used to evaluate and recondition "marginal," nonacceptable lungs. We have herein described an initial experience with ex vivo perfusion of 8 donor lungs deemed nonacceptable. MATERIALS AND METHODS: After harvesting, the lungs were perfused ex vivo with Steen Solution, an extracellular matrix with high colloid osmotic pressure. A membrane oxygenator connected to the circuit received gas from a mixture of nitrogen and carbon dioxide, maintaining a normal mixed venous blood gas level in the perfusate. The lungs were gradually rewarmed, reperfused, and ventilated for evaluation through analyses of oxygenation capacity, pulmonary vascular resistance (PVR), lung compliance (LC), and biopsy. RESULTS: The arterial oxygen pressure (with inspired oxygen fraction of 100%) increased from a mean of 206 mm Hg in the organ donor at the referring hospital to a mean of 498 mm Hg during the ex vivo evaluation. After 1 hour of EVLP, PVR varied from 440-1454 dynes/sec/cm(5); LC was in the range of 26-90 mL/cmH(2)O. There was no histological deterioration after 10 hours of cold ischemia and 1 hour of EVLP. CONCLUSIONS: The ex vivo evaluation model can improve oxygenation capacity of "marginal" lungs rejected for transplantation. It has great potential to increase lung donor availability and, possibly, reduce time on the waiting list. PMID- 20304160 TI - Experimental model of isolated lung perfusion in rats: first Brazilian experience using the IL-2 isolated perfused rat or guinea pig lung system. AB - INTRODUCTION: Lung transplantation has become the mainstay therapy for patients with end-stage lung disease refractory to medical management. However, the number of patients listed for lung transplantation largely exceeds available donors. The study of lung preservation requires accurate, cost-effective small animal models. We have described a model of ex vivo rat lung perfusion using a commercially available system. METHODS: Male Wistar rats weighing 250 g-300 g were anesthetized with intraperitoneal sodium thiopental (50 mg/kg body weight). The surgical technique included heart-lung block extraction, assembly, and preparation for perfusion and data collection. We used an IL-2 Isolated Perfused Rat or Guinea Pig Lung System (Harvard Apparatus, Holliston, Mass, United States; Hugo Sachs Elektronik, Alemanha). RESULTS: Preliminary results included hemodynamic and pulmonary mechanics data gathered in the experiments. CONCLUSION: The isolated rat lung perfusion system is a reliable method to assess lung preservation. PMID- 20304161 TI - Role of L-arginine, a substrate of nitric oxide biosynthesis, on intestinal ischemia-reperfusion in rabbits. AB - To study whether treatment with L-arginine (ARG), a substrate of nitric oxide biosynthesis, attenuates intestinal dysfunction caused by ischemia (I) and reperfusion (R), rabbits treated with ARG (100 mgxkg(-1), intravenously) or saline solution (SS) prior to I (60 minutes) by occlusion of superior mesenteric artery and/or during R (120 minutes). After I or I/R, 2-cm jejunal segments were isolated and mounted in an organ bath to study of neurogenic contractions stimulated by electrical pulses or KCl using a digital recording system. Thin jejunal slices were stained (hematoxylin and eosin) for analysis by optical microscopy. Compared to the sham group, jejunal contractions were similar in I + ARG, but reduced in I + SS, I/R + SS, and I/R + ARG groups. The jejunal enteric nerves were damaged in I + SS, I/R + SS, and I/R + ARG, but not in I + ARG group, suggesting that ARG can attenuate intestinal dysfunctions due to I, but not to R. PMID- 20304162 TI - Intestinal ischemia-reperfusion is attenuated by treatment with atenolol in rabbits. AB - To study whether treatment with the beta-blocker atenolol (AT) attenuates intestinal dysfunction caused by ischemia (I) and reperfusion (R), rabbits were treated with AT (1 mg.kg(-1), introvenously) or saline solution (SS) prior to I (60 minutes), which was produced by occlusion of the superior mesenteric artery, and/or R (120 minutes). After I or I/R, 2-cm jejunal segments were mounted in an organ bath to study neurogenic contractions stimulated by electrical pulses or KCl using a digital recording system. Thin jejunal slices were stained hematoxylin and eosin for analysis by optical microscopy. Compared to the sham group, the jejunal contractions were similar in the I + AT and the I/R + AT groups, but reduced in the I + SS and the I/R + SS groups. The jejunal enteric nerves were damaged in the I + SS and the I/R + SS groups, but not in the I + AT and the I/R + AT. These results suggest that AT may attenuate intestinal dysfunction caused by I and I/R. PMID- 20304163 TI - Role of adenosine on intestinal ischemia-reperfusion injury in rabbits. AB - To study if the treatment with adenosine (ADO), an agonist of adenosine receptors, attenuates intestinal dysfunction caused by ischemia (I) and reperfusion (R), we treated rabbits with ADO (15 mg x kg(-1), intravenously) or saline solution (SS) to I (60 minutes) before occlusion of superior mesenteric artery and/or R (120 min). After I or I/R, isolated jejunal segments (2 cm) were mounted in an organ bath to study nerve-mediated contractions stimulated by electrical pulses or KCl using a digital recording system. Thin jejunal slices were stained (hematoxylin and eosin) for analysis by optical microscopy. Compared to the sham group, the jejunal contractions were similar in I + ADO, but reduced in I + SS, I/R + SS, and I/R + ADO groups. We concluded that the jejunal enteric nerves were damaged in I + SS, I/R + SS, and I/R + ADO, but not in I + ADO group. These results suggested that ADO attenuated intestinal dysfunction due to I, but not to R. PMID- 20304164 TI - Effects of L-nitro-arginine methyl ester, an inhibitor of nitric oxide biosynthesis, on intestinal ischemia/reperfusion injury in rabbits. AB - To study whether treatment with L-nitro-arginine methyl ester (L-NAME), an inhibitor of nitric oxide biosynthesis, attenuates intestinal dysfunction caused by ischemia (I) and/or reperfusion (R), rabbits were treated with L-NAME (15 mgxkg(-1), intervenously) or saline olution (SS) prior to I (60 minutes) induced by occlusion of superior mesenteric artery and/or R (120 minutes). After I or I/R, isolated jejunal segments (2 cm) were mounted in an organ bath to study nerve-mediated contractions stimulated by electrical pulses or KCI using a digital recording system. Thin jejunal slices were stained (hematoxylin and eosin) for analysis by optical microscopy. Compared with a sham group, the jejunal contractions were similar in the I/R + L-NAME, but reduced in I + SS, I/R + SS, and I + L-NAME groups. The jejunal enteric nerves were damaged in the I + SS, I/R + SS, and I + L-NAME cohorts, but not among the I/R + L-NAME cohort. These results suggested that L-NAME attenuated intestinal dysfunction caused by R but not by I. PMID- 20304165 TI - Effects of 5'-adenosine triphosphate on intestinal ischemia-reperfusion in rabbits. AB - To study whether treatment with 5'-adenosine triphosphate (ATP), an agonist of P2 purine receptors, attenuated intestinal dysfunction caused by ischemia (I) and/or reperfusion (R), rabbits were treated with ATP (15 mgxkg(-1), intravenously) or saline solution (SS) 60 minutes before I by occlusion of the superior mesenteric artery and/or R (120 minutes). After I or I/R isolated 2-cm jejunal segments were mounted in an organ bath to study nerve-mediated contractions stimulated by electrical pulses or KCl using a digital recording system. Thin jejunal slices were stained (hematoxylin and eosin) for optical microscopy. Compared to a sham group, the jejunal contractions were similar to sham hosts among I + ATP, but reduced in I + SS, I/R + SS, and I/R + ATP groups. The jejunal-enteric nerves were damaged in I + SS, I/R + SS, and I/R + ATP, but not the I + ATP group. These results suggested that ATP attenuated intestinal dysfunction produced by I, but not that caused by R. PMID- 20304166 TI - Induction with basiliximab in renal transplantation. AB - INTRODUCTION: The use of monoclonal antibodies in renal transplantation for induction therapy has been associated with a marked reduction in acute rejection rates with an impact on graft and patient survivals. OBJECTIVE: We sought to evaluate the efficacy of renal transplant induction protocols using Basiliximab based on the rates of acute rejection episodes (ARE) and delayed graft function (DGF) of infectious complications in the first 6 months posttransplant, as well as patient and graft survivals. METHODS: We retrospectively evaluated all renal transplants performed between 2000 and 2008 that were primary grafts from cadaveric heart-beating donors, into recipients with a panel reactive antibody titer <5% and who were treated with an immunosuppression scheme based on cyclosporine, mycophenolate mofetil/mycophenolic acid plus corticosteroids, with (group 1) or without basiliximab (group 2). RESULTS: We enrolled 52 recipients in group 1 (induction with basiliximab) and 189 in group 2 (without basiliximab). The baseline characteristics were similar among the groups, except for time on dialysis which was longer in group 1 and the number of HLA matches, which was lower in group 1. The ARE rate was lower among group 1 (7.8% vs 27.8%; P = .001); rates of DGF and infectious complications were similar. There was no significant difference in graft and patient survivals. CONCLUSION: In this study, induction with basiliximab was associated with a reduced rate rate of ARE, despite a lower number of HLA matches and a longer previous time on dialysis. The use of this induction modality was not associated with a greater rate of infectious complications. PMID- 20304167 TI - Application of artificial neural networks in renal transplantation: classification of nephrotoxicity and acute cellular rejection episodes. AB - Complications associated with kidney transplantation and immunosuppression can be prevented or treated effectively if diagnosed in the early stages by posttransplant monitoring. One of the major problems is diseases that occur during the first year after kidney transplantation. For this purpose, we used different classifiers to predict events of nephrotoxicity versus acute cellular rejection episodes. The classifiers were evaluated according to values of sensitivity, specificity and area under ROC curves (RCA). The classifier with better accuracy rate for nephrotoxicity achieved the value of 75.68% and RCA classifier reached the accuracy of 80.89%. These results are encouraging, with rates of accuracy and error consistent with work purpose. PMID- 20304168 TI - Quantitative analyses of kidney injury molecule-1 messenger RNA in kidney transplant recipients with graft dysfunction. AB - BACKGROUND: Kidney injury molecule-1 (KIM-1), a type I transmembrane protein that is not expressed in normal renal tissue, shows increased expression in dedifferentiated cells within damaged regions of the proximal tubule. We evaluated mRNA transcription of the KIM-1 gene in renal tissue of kidney transplant patients who were experiencing graft dysfunction searching for an accurate biomarker of kidney graft injury. PATIENTS AND METHODS: mRNA analysis was performed on 59 biopsies from kidney transplant patients who had been classified according to the Banff 1997 scheme. Biopsies were categorized in 5 diagnostic groups: acute tubular necrosis (ATN) with superimposed acute rejection episode (ARE), ATN; ARE; calcineurin inhibitor nephrotoxicity (CIN); or interstitial fibrosis and tubular atrophy (IFTA). Amplified tissue RNA was quantified by real-time polymerase chain reaction. RESULTS: Renal tissue evaluations showed significantly increased KIM-1 mRNA expression as shown by median values, 25-75 percentiles, and averages of the logarithmic transformation: namely, CIN group (50.6; 1.8-285, 1; 1.24) and IFTA group (7.5; 1.26-14.6; 0.62), displayed significant differences (P > .05). In contrast, expression was lower among the ATN (0.47; 0.28-1.06; -0.13); ARE (0.21; 0.11-0.78; -0.45), and ATN+ARE (0.46; 0.06-3.27; -0.25) cohorts. CONCLUSION: These preliminary data suggested that KIM-1 mRNA might be useful biomarker of tubular damage associated with CIN and IFTA. PMID- 20304169 TI - Use of tacrolimus and the development of posttransplant diabetes mellitus: a Brazilian single-center, observational study. AB - INTRODUCTION: Posttransplant diabetes mellitus (PTDM) is considered to be a serious complication of kidney transplantation that may reduce patient and graft survival. The immunosuppressant tacrolimus (TAC) increases the risk of developing PTDM. PURPOSE: We sought to estimate the risk of PTDM among renal transplant recipients treated with TAC, to identify other risk factors for PTDM, and to describe its consequences. METHODS: We retrospectively analyzed 413 recipients of ages >or=18 years who were free of diabetes before kidney transplantation. They were treated with TAC, cyclosporine (CyA), or sirolimus (SIR) plus steroid therapy with a minimum follow-up posttransplant of 6 months. PTDM was diagnosed according to American Diabetes Association guidelines. RESULTS: The mean age was 42.3 years and 230 (55.7%) were male. The initial immunosuppression for 171 (41.4%) patients was TAC; 221 (53.5%), CyA; and 21 (5.1%), SIR. PTDM occurred in 85/413 (20.6%) of patients. The median time to PTDM development was 54 days posttransplant. The cumulative incidence of PTDM was 24.6% and 17.2% for TAC and CyA treatment groups, respectively. In the intention-to-treat analysis, the proportion of patients receiving TAC who developed PTDM was significantly higher than that of CyA (HR = 1.6 [1.01-2.42]; P = .04). The Kaplan-Meier method showed that 78.5% patients taking TAC were free of PTDM at 6 months compared with 88.8% taking CyA (P = .003). The other independent risk factors were body mass index (BMI; P < .0001); recipient age (P < .0001) and acute rejection episodes (AE; P = .01). Three-year actuarial graft survivals were 85.5% for PTDM patients compared with 93.3% for those without diabetes (P = .021); patient survivals, 88.9% and 96.7%, respectively (P = .017). CONCLUSION: The incidence of PTDM is associated with TAC use, recipient age, BMI, and ARE. Therefore, PTDM is an important risk factor for graft loss and mortality. PMID- 20304170 TI - Therapeutic option for infected urinary tract fistulas in renal transplantation. AB - BACKGROUND: Approximately 20% of urinary tract fistulas after renal allografting are complicated by urinary tract infection, which presents a therapeutic challenge. OBJECTIVE: To evaluate an option for treatment of urinary tract fistulas associated with urinary tract infection and unsuitable for minimally invasive or primary surgical urinary tract repair. PATIENTS AND METHODS: The study included 650 recipients who underwent transplantation over 17 years. Urinary leakage was initially treated with indwelling bladder catheterization. Patients with fistulas refractory to treatment underwent surgical intervention to repair the urinary tract. In patients who were not candidates for primary repair of the urinary tract, temporary urinary diversion was performed, rather than classic percutaneous or open nephrostomy, using a ureteral stent (ie, a 6F or 8F Foley catheter with the balloon placed inside the renal pelvis). RESULTS: Overall, urinary leakage occurred in 36 patients (5.5%). Conservative management was successful in 14 vesical fistulas (42.4%) and no ureteral fistulas (0%). Three patients died of sepsis during conservative treatment, before the new surgical approach. Five of 36 urinary leaks (13.9%) were managed using ureteral intubation with an 8F Foley catheter, with a success rate of 80%. CONCLUSION: Ureteral catheterization with an 8F Foley catheter is a feasible therapeutic option to treat complicated urinary tract fistulas unsuitable for primary surgical repair of the urinary tract. PMID- 20304171 TI - Urinary tract infections in renal transplant recipients: virulence traits of uropathogenic Escherichia coli. AB - BACKGROUND: Urinary tract infection (UTI) is the most common infectious complication after renal transplantation. Most infections are caused by uropathogenic Escherichia coli (UPEC). There are limited data on the prevalence of virulence traits among UPEC isolated from renal transplant recipients. This study compared the phenotypic and genotypic profiles of UPEC strains isolated from recipients with those from control patients. METHODS: E coli isolates that caused UTI in recipients versus nonimmunosuppressed control patients were characterized according to phylogenetic group and the presence of urovirulence genes pap1/pap2; sfa1/sfa2; afa1/afa2; aer1/aer2; and cnf1/cnf2. RESULTS: Thirty six UPEC isolates from recipients and another 27 from control individuals were included in the study. The proportion of episodes of pyelonephritis in recipients (50%) versus control subjects (41%) was similar (P = .46). However, secondary bacteremia was observed only among recipients (n = 8; P < .001). There was no significant difference in the distribution of phylogenetic groups or the prevalence of analyzed virulence traits between UPEC isolated from the 2 groups. Nevertheless, strains associated with secondary bacteremia in recipients showed a higher prevalence of mannose-resistant hemagglutination (P = .013). CONCLUSION: The phenotypic and genotypic characteristics of UPEC isolated from recipients were similar to those from control patients at a tertiary care center. Secondary bacteremia in recipients was associated with a higher prevalence of mannose resistant hemagglutination. PMID- 20304172 TI - Urinary tract infection caused by extended-spectrum beta-lactamase-producing bacteria in kidney transplant patients. AB - Urinary tract infection (UTI) is a common complication among kidney transplant patients. UTI caused by multi-resistant extended-spectrum beta-lactamase producing bacteria (ESBL) have largely increased among the hospitalized patient population and especially kidney transplant recipients. We retrospectively studied 83 kidney transplant patients to evaluate the incidence and possible causative conditions of ESBL-related UTI over the last 6 years. ESBL production was determined by the antibiotic susceptibility profile of urine cultures. We compared the incidence in two 3-year periods, 2003-2005 (period 1) and 2006-2008 (period 2). An high incidence of ESBL-related UTI (16.8%) was observed in the posttransplant period performing 31% of the overall UTI incidence, with an increase over the last 3 years from 23.8% to 37.5%. ESBL-related UTI was related to previous episodes of UTI (78.6% vs 29.0%; P < .01) and reoperations (50.0% vs 12.9%; P < .05). We observed a progressively increasing incidence of 13%, 38%, and 45% of ESBL-related UTI among first, second, and third episodes, respectively. Age, gender, HLA mismatches, etiology of chronic kidney disease, diabetes mellitus, acute rejection, induction treatment, and type/level of immunosuppressants were similiar between the groups with or without ESBL-related UTI. We observed a high increased incidence of ESBL-related UTI among kidney transplant recipients, and particularly patients with recurrent UTI. PMID- 20304173 TI - Serological profile of pretransplantation liver patients. AB - INTRODUCTION: A liver transplantation is the first choice of treatment for patients with hepatic insufficiency due to chronic diseases. Infections in the postoperative period represent one of the main causes of mortality in these cases. However, few articles have evaluated the predominance of certain infectious diseases and their influence on postoperative mortality. METHODS: We retrospectively evaluated the medical records of 236 patients who underwent liver transplantation from January 1997 to January 2007. In these records we checked the serological profiles for these diseases: toxoplasmosis, syphilis, human T lymphotropic virus (HTLV) I and II infection, Chagas disease, hepatitis A, hepatitis B, hepatitis C, paracoccidioidomycosis, tuberculosis, acquired immunodeficiency syndrome, cytomegalovirus (CMV), and mononucleosis (Epstein-Barr virus [EBV]). The statistical analysis was performed by table frequencies. RESULTS: CMV showed positivity (CMV-IgG) in 94.7% of patients, 95.8% for EBV, 33.3% for toxoplasmosis, 47.9% for hepatitis C, and 5% for hepatitis B. CONCLUSION: Our analysis showed the importance of serological investigations and diagnostic examinations before the transplantation procedure, seeking to minimize possible reactivation of the disease after the use of immunosuppression drugs, particularly in the first 6 months after transplantation, or even to avoid a primary infection. PMID- 20304174 TI - Red blood cell antigen alloimmunization in liver transplant recipients. AB - Orthotopic liver transplantation (OLT) is a life-saving procedure for patients with end-stage liver disease. Transfusion support is an important part of OLT. Intraoperative transfusion of large volumes of blood products is recognized to be a poor prognostic factor, probably due to the negative effects of blood transfusions, such as transfusion reactions, infectious contamination of blood products, or immune modulation of the transfused patient. The aim of this study was to evaluate the frequency of alloimmunization and its specificity to red blood cell (RBC) antigens among patients undergoing OLT. We identified 74 RBC alloantibodies in 70 (23%) patients when the indirect antiglobulin test (IAT) was performed. The most common RBC alloantibodies were against Rh system antigens. The majority (41.9%) were directed against the E antigen. Despite the ethnic heterogeneity of our population there were no cases of intravascular hemolysis. The incidence of alloimmunization (23%) was slightly higher among patients than in the literature, most probably as a consequence of our ethnic heterogeneity. PMID- 20304176 TI - Portal vein thrombosis and liver transplantation: long term. AB - Obstruction of the portal vein may be related to constriction by malignant tumors or thrombosis associated with liver disease. We herein have reported our experience with patients undergoing liver transplantation with portal vein thrombosis (PVT) whose diagnosis was made intraoperatively. From September 1991 to May 2009, we studied 27/419 (6.4%) patients with PVT who were evaluated according to the presence of esophagogastric varices, underlying disease, malignancy, and if there was previous surgery, review of medical records on data collected prospectively. We observed 24 (88.9%) patients with PVT grade 1, 2 (7.4%) with grade 2, and 1 (3.7%) with grade 3. The average age of the PVT patients was 47.5 years; the average model for End-Stage Liver Discase score was 18.3, and the predominant diagnosis, hepatitis C cirrhosis. Eighteen underwent a sclerotherapy/ligature. The sensitivity of ultrasound for grade 1 thrombosis was 39.1%; for grade 2, 50%; and for grade 3, 100%. Portal vein thrombectomy was performed in 24 patients. In other patients (grade 2), we performed an anastomosis of the donor portal vein to the recipient gastric vein or to a greater splanchnic collateral vein. In only 1 patient was the graft performed using the donor portal vein-donor iliac vein-recipient superior mesenteric vein. None of the patients displayed PVT in the immediate postoperative period. Actuarial survivals at the years 1, 3, and 5 were 85%, 74%, and 63%, respectively. We concluded that PVT cannot be considered to be a contraindication for liver transplantation. PMID- 20304175 TI - Liver transplantation in bearers of hepatitis B associated or not with delta hepatitis in the age of the new antiviral drugs: is hyperimmune globulin still necessary? AB - Hepatitis B (HBV) is a public health problem worldwide; one-third of the population has already been in contact with HBV, and 350 million people are chronic carriers of virus. The appearance of hyperimmune gamma globulin and antiviral drugs has allowed that group to undergone hepatic transplantation, achieving satisfactory results to prevent a relapse. But the use of hyperimmune gamma globulin has an extremely high cost, and combined therapies with new antiviral drugs seem to be a therapeutic alternative. We analyzed 21 patients with hepatitis B associated or not with Delta hepatitis over a mean follow-up period of 19.5 months, concluding that use of only nucleotide analogues has sufficient to achieve satisfactory results. PMID- 20304177 TI - Treatment of hepatocellular carcinoma with liver transplantation: a single-center experience from Brazil. AB - INTRODUCTION: Orthotopic liver transplantation (OLT) is the treatment of choice of hepatocellular carcinoma (HCC) for patients with cirrhosis, mainly those with early HCC. Herein we have present the clinical characteristics and outcomes of cirrhotic patients with HCC who underwent OLT from cadaveric donors in our institution. METHODS: From May 2001 to May 2009, we performed 121 OLT including 24 patients (19.8%) with cirrhosis and HCC within the Milan criteria. In 4 cases, HCC was an incidental finding in the explants. RESULTS: The patients' average age was 55 +/- 10 years, including 82% men. Fifty percent of patients were Child class B or C. The average Model for End Stage Liver Disease for Child A, B, and C categories were 11, 15, and 18, respectively. The HCC diagnosis was made by 2 dynamic images in 16 cases; 1 dynamic image plus alphafetoprotein >400 ng/mL in 4; and 4 by histologic confirmation. Twenty patients received a locoregional treatment before OLT: 6 percutaneous ethanol injection, 9 transarterial chemoembolization, 1 transarterial embolization, and 4 a combination of these modalities. The median follow-up after OLT was 19.7 months (range, 1-51). A vascular invasion was observed in the explant of 1 patient, who developed an HCC recurrence and succumbed at 8 months after OLT. Two further patients, without vascular invasion or satellite tumor displayed tumor recurrences at 7 and 3 months after OLT, and death at 2 and 1 month after the diagnosis. The remaining 25 patients have not shown a tumor recurrence. CONCLUSION: In the present evaluation, OLT patients with early HCC and no vascular invasion showed satisfactory results and good disease-free survival. Strictly following the Milan criteria for liver transplantation in patients with HCC greatly reduces but does not completely avoid, the chances of tumor recurrence. PMID- 20304178 TI - Histopathologic characteristics of incidental hepatocellular carcinoma after liver transplantation. AB - INTRODUCTION: Liver transplantation for patients with hepatocellular carcinoma (HCC) is an accepted therapeutic modality, depending on the size and number of nodules. Since a high incidence of incidental HCC at transplantation has been reported, our aim was to evaluate the histopathologic characteristics of these patients. PATIENTS AND METHODS: This retrospective analysis from March 1998 to June 2009 included liver transplantation patients without increased alpha fetoprotein or nodules on imaging methods. We included patients with HCC on anatomopathologic exam, excluding those presenting with HCC on the presurgery evaluation through clinical, laboratory and imaging methods. RESULTS: Among the 277 transplanted subjects, 27 showed incidental HCC. The alpha-fetoprotein average level was 8.52 mg/dL (1.6-28.2). One patient presented with adenomatosis and focus of HCC. Histopathologic analyses showed: mean tumor size was 0.9 cm (range = 0.4-3.5); average number of tumors in each explanted liver 1.85 (range = 1-7) nodules; and three (11.1%), microvascular invasion (11.1%). The TNM staging showed 17 (63%) stage I and 6 (22%) stage II. The Edmondson and Steiner classification showed 19 (70%) subjects in degree II. CONCLUSION: The histopathologic presentation of incidental HCC after liver transplantation showed tumors in early stage with microvascular invasion in some cases. PMID- 20304179 TI - Impact of liver ex situ transection on pediatric liver transplantation. AB - Ex situ hepatic transection (ESHT) has allowed transplantation of younger and smaller patients than whole liver grafts. Liver transection is a technical challenge due to the prolonged back table time, possible graft lesions, and increased surgical bleeding from the cut surface. We compare the outcomes of whole versus transected liver grafts in pediatric liver transplantation. METHODS: We retrospectively studied 41 pediatric patients who underwent 42 consecutive liver transplants (1 retransplant) from cadaveric donors. The study included all patients <18 years old who were transplanted at our institution from December 2001 to September 2009. Patients were distributed into 2 groups: whole organ (WO; n = 20) and transected liver grafts (TLG; n = 21). The ESHT grafts included 17 splits and 5 reduced size livers. We evaluated the age, weight, blood component transfusions, 1-year survival, laboratory tests at 2nd and 7th days postoperatively, surgical complications, reoperations, rejection episodes, cold ischemia time, biliary reconstruction type, and donor laboratory tests. Data were analyzed using Fisher and Student's t-tests. RESULTS: The mean age was 115 months (range, 7 months to 17.6 years) in the WO group and 43.3 months (range, 5 months to 16.25 years) in the TLG group (P = .0003). Mean weight was 19.8 kg (range, 5.8 67) and 9.7 Kg (range, 5.2-57) in the WO and TLG groups, respectively (P = .0079). Red blood cell transfusion was higher in the TLG group (P = .0479). Laboratory tests showed no difference between the 2 groups considering hepatic lesions or function markers. One-year patient survivals were 90% and 85.8% among the WO and LTG, respectively (P = .588). The overall 1-year survival rate was 88.8%. CONCLUSION: ESHT allowed smaller and younger children to be transplanted. There was an increased necessity of red blood cell transfusions after hepatic transection. There was no impact on liver function or 1-year patient or graft survival after ESHT. PMID- 20304180 TI - Analysis of survival after primary liver transplantation: multivariate analysis of 155 cases in a single center. AB - Liver transplantation is known as a highly complex procedure. Several variables can affect the outcome. The present study is a retrospective multivariate analysis of the outcomes of primary liver transplant recipients from deceased donors. From November 2006 through January 2009, 155 patients received first liver transplants from deceased donors. The data included the following: age of the recipient, gender of the recipient, ABO type, indication for the transplantation, model for end-stage liver disease (MELD) score, operative time, donor age, gender of the donor, cold ischemia time, and quantity of transfused blood products-red blood cells (PRBC), red blood cells recovered during the operation (cell saver), platelets, and fresh frozen plasma. Statistical analysis was done using SPSS 17 software. Cox regression analysis was performed to identify significant variables. ROC (receiver operating characteristic) curve was applied for those significant factors. Among all variables, only PRBC transfusion and MELD score showed statistical significance. For PRBC the increment of death risk was 17.08%, and for MELD score it was 3.83%. Patients that had to use PRBC and higher MELD scores had worse survivals. We concluded that the requirement for red blood cell transfusions and MELD showed the most significant influences on the outcomes of adult liver transplantations from deceased donors. PMID- 20304181 TI - Anxiety levels observed in candidates for liver transplantation. AB - INTRODUCTION: Anxiety can be considered an emotional state that does not present itself at the same intensity in all patients, and can be classified into 3 levels: mild, moderate, and severe. The patient, upon entering the waiting list for transplantation, reflects on the decision taken, which leaves him constantly anxious about the idea of possible death. OBJECTIVE: This study had the aim of evaluating the degree of anxiety observed in orthotopic liver transplantation (OLT) candidates and whether there was a correlation between anxiety and etiologic diagnosis. METHODS: This study was a prospective study where the patients underwent psychological evaluation by Beck Anxiety Inventory (BAI). The anxiety level was minimal, mild, moderate, or severe. The Model for End-Stage Liver Disease (MELD) score and etiology were recorded. RESULTS: The level of anxiety found were as follows: 55% minimal, 27% mild, 12% moderate, and 7% severe. The correlation between level of anxiety and etiologic diagnosis showed that 71% of patients with alcoholic cirrhosis and 60% of those with liver cancer showed a minimal degree of anxiety and 27% of patients with autoimmune cirrhosis had severe anxiety. CONCLUSION: We found that in patients with autoimmune hepatitis, the degree of anxiety was more pronounced. It is believed that the absence of physical symptoms is an important factor when observing anxiety in OLT candidates. PMID- 20304182 TI - Biliary complications following deceased and living donor liver transplantation: a review. AB - INTRODUCTION: Biliary complications are the most important source of complications after liver transplantation, and an important cause of morbidity and mortality. With the evolution of surgical transplantation techniques, including living donor and split-liver transplants, the complexity of these problems is increasing. Many studies have shown a higher incidence of biliary tract complications in living donor liver transplantation (LDLT) compared with deceased donor liver transplantation (DDLT). This article reviews biliary complications after liver transplantation and correlations with LDLT and DDLT. OBJECTIVE: Provide an overview of biliary complications among LDLT and DDLT. RESULTS: The incidence of biliary complications is higher among LDLT (28.7%) when compared with DDLT (15.5%). Bile leaks were the most common complication due to LDLT (17.1%); however, stricture was the most common complication due to DDLT (7.5%). PMID- 20304183 TI - Prevalence of posttransplantation lymphoproliferative disease in pediatric liver transplant recipients. AB - OBJECTIVE: The objective of this study was to identify the incidence of posttransplantation lymphoproliferative disease (PTLD) among children within 1 year after liver transplantation. METHODS: This retrospective review analyzed information in medical charts of pediatric (younger than 18 years of age) recipients of liver transplants between September 2000 and December 2007. RESULTS: Seventy-one patients underwent a liver transplantation and 7 (9.85%) developed PTLD. Among this group, 6 children were girls and 1 was a boy. The median age at transplantation was 35.14 months. Indications that led the children to have their transplantation were 1 case of hemangioendothelioma, 1 case of autoimmune hepatic cirrhosis, 1 case of alpha-1-antitrypsin deficiency, and 4 cases of biliary atresia. The most frequent symptoms were splenomegaly, diarrhea, and fever. The median time from the first symptoms to the initial treatment was 9.7 days. The standard treatment was withdrawal of immunosuppression and close observation of tacrolimus levels and liver function tests associated with antiviral drugs and chemotherapy. Four among 7 children died; 3 children recovered. All 3 children who recovered has presented at the transplantation center within 5 days of initiation of symptoms (P = .033896). CONCLUSION: Despite its rarity, when it occurs, PTLD shows a high mortality rate. Therefore, it is necessary to have interdisciplinary work between the medical team that performs the transplantation and those promoting the primary care to diagnose the disease early and treat it effectively. PMID- 20304184 TI - Impact of cytomegalovirus infection in lung transplant patients under universal prophylaxis: single-center experience in Brazil. AB - INTRODUCTION: Cytomegalovirus (CMV) infection, a common complication in lung transplant (LT) patients, is associated with worse outcomes. Therefore, prophylaxis and surveillance with preemptive treatment is recommended. OBJECTIVES: Describe the epidemiology and impact on mortality of CMV infection in LT patients receiving CMV prophylaxis. METHODS: Single-center retrospective cohort of LT recipients from August 2003 to March 2008. We excluded patients with survival or follow-up shorter than 30 days. We reviewed medical charts and all CMV pp65 antigen results. RESULTS: Forty-seven patients met the inclusion criteria and 19 (40%) developed a CMV event: eight CMV infections, seven CMV syndromes, and 15 CMV diseases. The mean number of CMV events for each patient was 1.68 +/- 0.88. Twelve patients developed CMV events during prophylaxis (5/12 had CMV serology D+/R-). Forty-six of the 47 patients had at least one episode of acute rejection (mean 2.23 +/- 1.1). Median follow-up was 22 months (range = 3 50). There were seven deaths. Upon univariate analysis, CMV events were related to greater mortality (P = .04), especially if the patient experienced more than two events (P = .013) and if the first event occurred during the first 3 months after LT (P = .003). Nevertheless, a marginally significant relationship between CMV event during the first 3 months after LT and mortality was observed in the multivariate analysis (hazards ratio: 7.46; 95% confidence interval: 0.98-56.63; P = .052). Patients with CMV events more than 3 months post-LT showed the same survival as those who remained CMV-free. CONCLUSION: Prophylaxis and preemptive treatment are safe and effective; however, the patients who develop CMV events during prophylaxis experience a worse prognosis. PMID- 20304185 TI - Cytokine profile in pleural fluid and serum after lung transplantation. AB - BACKGROUND: Lung transplantation is the procedure of choice in several end-stage lung diseases. Despite improvements in surgical techniques and immunosuppression, early postoperative complications occur frequently. OBJECTIVE: To evaluate the pleural inflammatory response after surgery. PATIENTS AND METHODS: Twenty patients aged 18 to 63 years underwent unilateral or bilateral lung transplantation between August 2006 and March 2008. Proinflammatory cytokines interleukin (IL)-1beta, IL-6, and IL-8 and vascular endothelial growth factor in pleural fluid and serum were analyzed. For cytokine evaluation, 20-mL samples of pleural fluid and blood (right, left, or both chest cavities) were obtained at 6 hours after surgery and daily until removal of the chest tube or for a maximum of 10 days. Data were analyzed using analysis of variance followed by the Holm-Sidak test. RESULTS: All effusions were exudates according to Light's criteria. Pleural fluid cytokine concentrations were highest at 6 hours after surgery. Serum concentrations were lower than those in pleural fluid, and IL-1beta, IL-6, and IL 8 were undetectable at all time points. CONCLUSIONS: There is a peak concentration of inflammatory cytokines in the first 6 hours after transplantation, probably reflecting the effects of surgical manipulation. The decrease observed from postoperative day 1 and thereafter suggests the action of the immunosuppression agents and a temporal reduction in pleural inflammation. PMID- 20304186 TI - Validation of a cutoff value on echo Doppler analysis to replace right heart catheterization during pulmonary hypertension evaluation in heart transplant candidates. AB - BACKGROUND: Heart transplantation (OHT) has traditionally been contraindicated in the presence of severe pulmonary hypertension (PH), as detected by right heart catheterization. Noninvasive methods are still not reliably accurate to make this evaluation. OBJECTIVES: Determine the efficacy of echo Doppler analysis for the diagnosis of severe PH. METHODS: One hundred thirty patients (mean age = 42 +/- 15 years, 82 men) showed severe left ventricular dysfunction (mean ejection fraction = 29 +/- 12%; functional class III-IV). We excluded patients with atrial fibrillation, heart failure secondary to congenital disease, and valvulopathy. The pulmonary parameters defined as severe PH were: systolic pulmonary artery pressure (sPAP) >or= 60 mm Hg; a mean transpulmonary gradient >or= 15; or pulmonary vascular resistance >or= 5 Wood units. Patients underwent a right heart catheterization using a Swan-Ganz catheter to measure hemodynamic parameters and to noninvasively estimate right-sided pressures from spectral Doppler recordings of tricuspid regurgitation velocity (right ventricular systolic pressure [RVsP]). A Pearson correlation of sPAP was obtained with RVsP by; the sensitivity of RVsP for the diagnosis of PH was determined by a receiver operating characteristic (ROC) curve. RESULTS: A good correlation between sPAP and RVsP was obtained by Pearson correlation analysis (r = 0.64; 95% confidence interval [CI] 0.50-0.75; P < .001). The ROC curve analysis showed a sensitivity of 100%, a specificity of 37.2%, (95% CI 0.69-0.83, P < .0001) of a RVsP < 45 mm Hg (cutoff) on the exclusion of severe PH. CONCLUSIONS: The cutoff of RVsP < 45 mm Hg, on noninvasive echo Doppler evaluation of PH is an efficient method to replace invasive heart catheterization in OHT candidates. PMID- 20304187 TI - Dobutamine stress echocardiography in heart transplant recipients' evaluation: the role of reinnervation. AB - INTRODUCTION: Orthotopic heart transplantation renders the recipient denervated. This remodeling of the intrinsic cardiac nervous system should be taken in account during functional evaluation for allograft coronary artery disease. Dobutamine stress echocardiography (DSE) has been used to detect patients at greater risk. The aim of this study was to determine whether patients with various autonomic response levels, and supposed reinnervation patterns, show the same response to DSE. METHODS: We studied 20 patients who had survived more than 5 years after orthotopic heart transplantation. All patients underwent a Holter evaluation. We considered patients with low variability to be those with less than a 40-bpm variation from the lowest to highest heart rate, so-called "noninnenervated" (group NI). Patients who had 40-bpm or more variation were considered to show high variability and called "reinnervated" (group RI). After that, all patients performed an ergometric test and DSE. RESULTS: Groups were defined as NI (n = 9) and RI (n = 11). Ergometric tests confirmed this response with NI patients showing less variability when compared to RI patients (P = .0401). During DSE, patients showed similar median heart rate responses according to the dobutamine dose. Spearmen correlation showed r = 1.0 (P = .016). CONCLUSIONS: DES was effective to reach higher heart rates, probably related to catecholamine infusion. These findings may justify a better response when evaluating cardiac allograft vasculopathy in heart transplant patients. PMID- 20304188 TI - Recovery of renal function in heart transplantation patients after conversion from a calcineurin inhibitor-based therapy to sirolimus. AB - BACKGROUND: Renal failure is the most important comorbidity in patients with heart transplantation, it is associated with increased mortality. The major cause of renal dysfunction is the toxic effects of calcineurin inhibitors (CNI). Sirolimus, a proliferation signal inhibitor, is an imunossupressant recently introduced in cardiac transplantation. Its nonnephrotoxic properties make it an attractive immunosuppressive agent for patients with renal dysfunction. In this study, we evaluated the improvement in renal function after switching the CNI to sirolimus among patients with new-onset kidney dysfunction after heart transplantation. METHODS: The study included orthotopic cardiac transplant (OHT) patients who required discontinuation of CNI due to worsening renal function (creatinine clearance < 50 mL/min). We excluded subjects who had another indication for initiation of sirolimus, that is, rejection, malignancy, or allograft vasculopathy. The patients were followed for 6 months. The creatinine clearance (CrCl) was estimated according to the Cockcroft-Gault equation using the baseline weight and the serum creatinine at the time of introduction of sirolimus and 6 months there after. Nine patients were included, 7 (78%) were males and the overall mean age was 60.1 +/- 12.3 years and time since transplantation 8.7 +/- 6.1 years. The allograft was beyond 1 year in all patients. There was a significant improvement in the serum creatinine (2.98 +/- 0.9 to 1.69 +/- 0.5 mg/dL, P = .01) and CrCl (24.9 +/- 6.5 to 45.7 +/- 17.2 mL/min, P = .005) at 6 months follow-up. CONCLUSION: The replacement of CNI by sirolimus for imunosuppressive therapy for patients with renal failure after OHT was associated with a significant improvement in renal function after 6 months. PMID- 20304190 TI - Pancreas-kidney transplantation: complications and readmissions in 9-years of follow-up. AB - Over 9 years, we have performed 93 simultaneous pancreas-kidney transplants (SPKT). The morbidity of this procedure is high compared with kidney transplantation alone; readmissions are frequent and costs are higher. Herein we have presented the complications during follow-up of these 93 patients. Their mean age was 34 +/- 6 years and prior dialysis time was 32 +/- 25 months. The median hospital stay on the first admission for the transplant procedure was 22 days, including 2 days in the intensive care unit. Bleeding, thrombosis, and infection were the most frequent reasons for prolonged hospitalization. Thirty patients underwent >or=1 surgical reinterventions. Incidence of acute rejection episodes was 11.8%. After discharge, 74.2% of the patients had 197 readmission episodes with infection being the main cause, urinary tract infections, the most frequent; however, systemic viral and fungal infections required the longest readmission periods. The need for surgical interventions, graft dysfunction, and vascular problems were the remaining causes of readmission. At the end of follow up, 87 patients were alive, 86 with well-functioning kidneys and 74 with normal functioning pancreata. Global survival rates for patient, kidney, and pancreas were 96%, 95%, and 81% at 1-year; 93%, 90%, and 79% at 5-years; and 93%, 90% and 79% at 9-years. Although pancreas-kidney transplant patients are complex presenting many management difficulties, our overall results represent a positive stimulus for diabetic patients. PMID- 20304189 TI - Multivariate analysis of risk factors for early loss of pancreas grafts among simultaneous pancreas-kidney transplants. AB - To evaluate the risk factors for pancreas graft loss within 3 months postoperatively among 170 simultaneous pancreas-kidney transplantation (SPKT) we examined 38 variables. METHODS: Twenty-two variables were related to recipients; 12 to donors and 4 to the surgical procedure. In addition the latest follow-up dates as well as the transplant and/or death dates. Independent variables were examined with reference to the dependent pancreatic loss variable, excluding losses owing to deaths. Variables with statistical significance were analyzed to predict early graft loss. RESULTS: Univariate analyses determined the following significant variables: kidney cold ischemia time, older donors, non-white donors, death cause related to vascular disease, wound infection, and length of extended hospitalization. However, multivariate analysis showed that only donor age and kidney cold ischemia time were significant predictors for early pancreatic graft loss. CONCLUSION: Donor age and kidney cold ischemia time were independently related to pancreatic loss after SPKT within 3 months posttransplantation. PMID- 20304191 TI - Bone mineral density after simultaneous kidney-pancreas transplantation: four years follow-up of 57 recipients. AB - Bone disease and an high risk of fractures are major problems in transplantation. Among diabetic patients undergoing simultaneous kidney-pancreas (SKP) transplantation, there are few studies assessing long-term effects on bone mass. The aim of this study was to evaluate bone mineral density (BMD) over 4 years follow-up after SKP transplantation. Fifty-seven patients had 22.8 +/- 5.3 years of prior diabetes, 65% were female, and the overall mean age was 24.3 +/- 5.93 years. At the time of transplantation, the lumbar spine and femoral neck T-scores were -1.75 +/- 1.05 and -1.95 +/- 0.73, respectively; 28% of subjects had evidence of osteoporosis. One year after transplantation, 77.6% of patients displayed improved lumbar T-scores to -1.33 +/- 0.94 (P = .044) with stable femoral neck T-scores. Bone densitometry enhanced gradually through the 4 years follow-up: lumbar T-score to -1.04 +/- 0.67 (P = .004) and femoral neck T-score to -1.69 +/- 0.49 (P = .12). At year 4, no osteoporosis cases were detected but 86.7% of patients did not receive steroids in the immunosuppressive regimen. The graft function remained stable (serum creatinine, 1.2 mg/dL; fasting glucose, 87.7 mg/dL). During the follow-up, BMD improved more significantly at cortical sites. Our study reports a reduced prevalence of fractures (8.7%) compared with the literature, which could be related to a steroid-sparing protocol and/or aggressively treatment of osteoporosis. PMID- 20304192 TI - Analysis of reoperations and their impact on the results of pancreas transplantation. AB - BACKGROUND: Many factors, including the advances in surgical techniques and immunosuppression, have been brought significant improvement to graft and patient survivals of patients undergoing pancreatic transplantations. However, one third of these patients require reoperations (ReOps). PURPOSE: We sought to evaluate the distribution of ReOps in the early or late postoperative period and analyze their impact on patient and graft survivals. PATIENTS AND METHODS: This unicenter, retrospective study was performed using data from 182 patient charts after pancreas transplantation from January 2000 through December 2007. RESULTS: We performed 88 ReOps on 73 patients; 43 early and 41 late operations. The simultaneous pancreas-kidney transplantation group showed a greater incidence of premature ReOps. The group undergoing early ReOp showed a lower survival rate (87.2%) compared with the nonoperated group, but a similar survival rate (97.5%) to the late ReOp group. In relation to the survival of pancreatic grafts after 1 year, the early ReOp group showed inferior survival to the late ReOp group, both of which were significantly worse results then those of the group without ReOp. CONCLUSION: ReOps were related to the success of the procedure. When they were performed in the first 3 months they had a negative impact on patient and graft survival. PMID- 20304193 TI - Expression of pancreatic endocrine markers by mesenchymal stem cells from human umbilical cord vein. AB - BACKGROUND: Mesenchymal stem cells (MSCs) from human umbilical cord vein have great potential for use in cell therapy because of their ease of isolation, expansion, and differentiation, in addition to their relative acceptance from the ethical point of view. Obtaining the umbilical cord at birth does not present any risk to either mother or child. OBJECTIVE: To isolate and promote in vitro expansion and differentiation of MSCs from human umbilical cord vein into cells with a pancreatic endocrine phenotype. METHODS: Mesenchymal stem cells obtained from human umbilical cord vein via collagenase digestion were characterized at cytochemistry and fluorescent-activated cell sorting, and expanded in vitro. Differentiation of MSCs into an endocrine phenotype was induced using high glucose (23 mmol/L) medium containing nicotinamide, exendin-4, and 2 mercaptoethanol. Expression of insulin, somatostatin, glucagon, and pancreatic and duodenal homeobox 1 was analyzed using immunofluorescence. RESULTS: Cells isolated from the umbilical cord vein were MSCs as confirmed at cytochemistry and fluorescent-activated cell sorting. Expression of somatostatin, glucagon, and pancreatic and duodenal homeobox 1 by differentiated cells was demonstrated using immunofluorescence. Insulin was not expressed. CONCLUSIONS: The MSC differentiation protocol used in the present study induced expression of some endocrine markers. Insulin was not produced by these cells, probably because of incomplete induction of differentiation. PMID- 20304194 TI - Expression of pancreatic endocrine markers by prolactin-treated rat bone marrow mesenchymal stem cells. AB - BACKGROUND: Mesenchymal stem cells (MSCs) are an attractive source for generation of cells with beta-cell properties. Previous studies have demonstrated the ability of prolactin to induce an increase in beta-cell mass and maturation, which suggests beneficial effects of its use in MSC differentiation protocols. OBJECTIVE: To evaluate the expression of endocrine differentiation markers in rat MSCs treated in vitro with prolactin. METHODS: Mesenchymal stem cells from bone marrow of Wistar rats were isolated, expanded, and characterized. Differentiation of MSCs was induced in medium containing 23 mmol/L of glucose, and nicotinamide, 2-mercaptoethanol, and exendin-4, in the presence or absence of 500 ng/mL of rat recombinant prolactin. Expression of endocrine markers and prolactin receptor genes was evaluated using real-time polymerase chain reaction, and compared between culture stages and presence vs absence of prolactin in the culture medium. Expression of insulin, somatostatin, glucagon, and pancreatic and duodenal homeobox 1 was also evaluated at immunofluorescence microscopy. RESULTS: Isolated cells were mostly MSCs, as confirmed at fluorescent-activated cell sorting and cytochemistry. Pax6, Ngn-3, Isl1, NeuroD1, Nkx2.2, and Nkx6.1 exhibited varied expression during culture stages. The long form of the prolactin receptor messenger RNA was induced in prolactin-treated cultures (P < .05). The somatostatin gene was induced in early stages of differentiation (P < .05), and its expression was induced by prolactin, as confirmed using immunofluorescence. CONCLUSION: Culture of rat bone marrow MSCs in differentiation medium induces expression of pancreatic endocrine-specific genes, and somatostatin and prolactin receptor expression was also induced by prolactin. PMID- 20304195 TI - Cell phenotype evaluation at various sites after skin transplantation and FTY720 plus sirolimus therapy. AB - Cell phenotype evaluation enables better understanding of the rejection process in experimental transplantation. We studied allograft survival and the mechanisms associated with rejection in a murine model of skin transplantation in the absence of immunosuppression or after FTY720 or sirolimus (SRL) administration for 21 days. Leukocyte phenotype was evaluated in the peripheral blood, spleen, axillary lymph nodes, thymus gland, and skin graft using flow cytometry at 5 days posttransplantation. Treatment with FTY720 plus SRL increased skin allograft survival in association with lymphopenia, reduced CD11b+ and CD3+CD4+ cell percentages in the graft, decreased CD3+CD4+, CD3+CD8+, and CD11b+ cell counts in lymphoid organs, and decreased CD4+CD8+ cell count in the thymus. These results suggest that increased allograft survival in animals treated with FTY720 plus SRL is due to possible impairment of antigen presentation or recognition in the graft and secondary lymphoid organs, and decreased emigration of mature thymocytes to the periphery. PMID- 20304196 TI - Leishmania (Leishmania) amazonensis infection in mice treated with FTY720. AB - In transplantation, parasite diseases are transmitted from the donor, or appear as de novo infections, or activate from a dormant insource as a consequence of immunosuppression. Clinical findings have shown that an intact immune system is crucial to prevent recurrence of Leishmania infection. We used BALB/c and C57BL/6 mice to evaluate the role of FTY720 in leishmaniasis. Mice inoculated with Leishmania (Leishmania) amazonensis were followed over 7 weeks for foot thickness measurements after initiation of FTY720 treatment. After 10 days of treatment, spleen, blood, and the foot were harvested for evaluation. BALB/c showed greater evident foot thickness than C57BL/6 mice. Oral treatment with FTY720 (1 mg/kg/d) over 10 days produced the same outcome. Increases in CD4(+) and CD8(+) T cells were observed after infection; FTY720 treatment was associated with a decrease in CD4(+) T cells only in BALB/c mice, whereas CD8(+) T cells were decreased in both mice strains. CD11b(+) expression decreased after infection with a discrete increase after FTY720 treatment. Lymphopenia was observed among all FTY720 treated mice. In conclusion, we observed that FTY720 produced no worse an outcome as monotherapy in established infections with L (L) amazonensis. PMID- 20304197 TI - Sirolimus in combination with FTY720: analysis of urinary and serum parameters. AB - The goal in transplantation is to obtain immunosuppressant combinations that decrease the incidence of acute and chronic rejection but cause fewer side effects. FTY720 is a new immunomodulator that prevents experimental allograft rejection without inhibiting T-cell activation. It is currently under clinical investigation for multiple sclerosis. We investigated whether FTY720 in combination with sirolimus (SRL) could cause renal toxicity in C57BL/6 mice when administered for 21 days. Serum creatinine and 24-hour urinary creatinine concentrations were assessed by enzymatic colorimetric assays. Urinary protein concentration was measured by the Bradford protein assay. Whereas serum creatinine levels were increased in FTY720 + SRL-treated animals, there were no changes in urinary volume, urinary protein levels, serum urea concentration, creatinine clearance, and kidney structure. Our findings suggested that FTY720 monotherapy for multiple sclerosis and other diseases could play an important immunomodulatory role without causing the side effects frequently observed with other transplantation regimens. PMID- 20304198 TI - Effectiveness of thalidomide and tamoxifen in preventing neointimal hyperplasia in experimental vascular injury in rats. AB - INTRODUCTION: Chronic allograft vasculopathy is an important cause of graft loss. Considering the inflammatory response in the development of chronic vascular lesions, therapeutic approaches to target the inflammatory process may be useful. We sought to investigate the possible protective effects on balloon catheter induced vascular injury of thalidomide and tamoxifen, 2 drugs with powerful anti inflammatory, immunomodulatory, and antifibrotic effects, using an animal model that mimics the morphologic features of chronic allograft vasculopathy. METHODS: Male Wistar rats subjected to balloon catheter carotid injury (INJ) were treated with thalidomide (100 mg/kg), or tamoxifen (10 mg/kg), or vehicle. Contralateral right carotid arteries were used as uninjured controls. Morphometric and immunohistochemical analyses were performed at 14 days postinjury. RESULTS: Injured carotid arteries showed marked neointimal hyperplasia, which was significantly inhibited among animals treated with thalidomide or tamoxifen: neointimal/media ratios of 1.4 +/- 0.4 versus 0.2 +/- 0.1 versus 0.4 +/- 0.2, for INJ, INJ + Thalid, and INJ + Tamox; respectively (P < .001). The endothelial cell loss was significantly less pronounced among animals subjected to carotid balloon injury that were treated with thalidomide (24 +/- 14 vs 1 +/- 1 cells per section in INJ, respectively (P < .05). Therapy with either thalidomide or tamoxifen effectively maintained alpha-smooth muscle actin expression in the media, similar to uninjured arteries. In this setting, tamoxifen was additionally effective to prevent the migration of myofibroblasts in to the intima. CONCLUSION: Thalidomide and tamoxifen were effective to reduce neointimal hyperplasia secondary to vascular damage. The vasculoprotective effects of thalidomide were more pronounced to preserve endothelial cells, whereas tamoxifen inhibited smooth muscle cell migration and proliferation. A possible beneficial effect of combined therapy with thalidomide plus tamoxifen should be addressed in future studies. PMID- 20304199 TI - Simultaneous pancreas-kidney transplantation in a human immunodeficiency virus positive recipient: a case report. AB - BACKGROUND: After the development of highly active antiretroviral therapy (HAART) for patients with human immunodeficiency virus (HIV), there has been increased interest in organ transplantation for this selected population. There is a lack of reports about pancreas transplant in HIV+ recipients. CASE REPORT: We report the case of a 43-year-old HIV+ man who presented with type 1 diabetes for 25 years and end-stage-renal disease. He underwent dialysis therapy for the prior 3 years. His CD4 count was 830 cells/mL and a negative viral load was achieved after 3 months of antiretroviral therapy. His nutritional status was favorable; no opportunistic infections had occurred. A simultaneous pancreas-kidney transplantation (SPKT) was performed from a 19-year-old deceased trauma victim. Pancreas implantation was enteric-portal drainage. No induction immunosuppression was used, but rather tacrolimus, sodium mycophenolate, and steroids. In the postoperative period, there was a delayed kidney graft function requiring hemodialysis for 14 days. On postoperative day 11, a kidney biopsy specimen showed mild rejection, which was successfully treated with steroids. The patient was discharged after 22 days; he was normoglycemic and insulin-independent with a serum creatinine value of 1.9 mg/dL. Currently, his outcome has been uneventful, without a readmission or opportunistic infections. After 5 months postoperation, the viral load is negative and the CD4 count is 460 cells/mL. The current serum creatinine level is 1.1 mg/dL; no insulin has been required. COMMENT: HIV has been considered to be an absolute contraindication to organ transplantation, because of the infection risk due to severe immunosuppression, to interactions between antiretroviral and immunosuppressive drugs, and to reluctance to offer an organ to a terminal patient. However, transplants in HIV+ patients have shown good results, when a patient has an acceptable CD4 level, a low viral load, and minimal antiretroviral therapy. PMID- 20304200 TI - Cephalic duodenopancreatectomy in the treatment of a bleeding duodenal ulcer in a pancreas recipient: a case report. AB - Pancreas transplantation is currently the only known therapy to restore glycemic metabolism in type 1 diabetic patients. Its most prevalent indication is in association with kidney transplantation (simultaneous pancreas and kidney transplantation SPK) for patients with type 1 diabetes mellitus (DM1) and nephropathy, who are under dialysis treatment. Surgical reinterventions, especially those resulting from complications of bladder exocrine pancreatic drainage, are associated with considerable morbidity and mortality. In this report, we present a clinical case of a 31-year-old Caucasian man with DM1 from 12 years of age and hemodialysis for 2 years before undergoing SPK 2 years prior. He then developed massive hematuria owing to a bleeding duodenal graft ulcer. The use of a segmental pancreatic technique with pancreaticocystostomy for exocrine pancreatic drainage allowed the maintenance of the graft and an euglycemic state in the patient, free of exogenous insulin. PMID- 20304201 TI - Ectopic placement of Sengstaken-Blakemore device to correct outflow obstruction in liver transplantation: case reports. AB - Liver transplantation is a complex procedure that has become the treatment for some end-stage liver diseases. Some technical features are important for the success of the transplantation, including the patency of the vascular anastomoses. In cadaveric whole organ liver transplantation, a large right subphrenic space may contribute to a twist of the inferior vena cava, leading to outflow obstruction, simulating an acute Budd-Chiari syndrome. Some devices can be used to correct this drainage problem. Herein, we have described 2 cases in which the Sengstaken-Blakemore balloon was safely used, in an ectopic position, to fix drainage complications in whole liver orthotopic transplantation. PMID- 20304202 TI - Cellulitis and nodular skin lesions due to Fusarium spp in liver transplant: case report. AB - Fusariosis is one of the emerging invasive fungal infections over the last decade. However, its recent rise has been in its ability to produce disseminated infection in severely immunosuppressed patients with neutropenia. In solid organ transplantation, fusariosis remains an uncommon picture mainly with nodules, subcutaneous abscesses, ulcers, or necrotic skin lesions resembling erthyma gangrenosum. Herein, we have reported a case of cellulitis, subcutaneous nodules, and abscesses due to Fusarium spp in a liver transplantation patient who was successfully treated with polyenes and surgical resection. PMID- 20304203 TI - Methylene blue used as a bridge to liver transplantation postoperative recovery: a case report. AB - Hepatopulmonary syndrome is defined as a triad of liver disease, arterial hypoxemia, and intrapulmonary vascular dilatation. The clinical hallmark of this disorder is the impairment of pulmonary gas exchange, not necessarily correlated with the severity of the underlying liver disease. Liver transplantation (OLT) is the only definitive treatment for this syndrome. However, patients with preoperative partial pressure of arterial oxygen (PaO(2)) under 50 mm Hg are exposed to an unacceptably high postoperative mortality and morbidity. Herein we have described a case of a 15-year-old female patient who underwent OLT and was treated with methylene blue in the early postoperative period to improve hypoxemia. We suggest that the use of methylene blue after liver transplantation can decrease postoperative complications and mortality rates in these patients. PMID- 20304204 TI - The 21st Congress of the Spanish Liver Transplantation Society (SETH). Preface. PMID- 20304205 TI - Liver transplantation: where we are and where we are heading. AB - Outcomes after liver transplantation are outstanding; however, the limiting factor is the shortage of organs. Recently, the utilization of donors after cardiac death has been encouraged; however, such transplants are associated with a high complication rate, mainly a high incidence of biliary complications, particularly ischemic cholangiopahty, a serious complication that often leads to retransplantation. The second problem is the morbidity associated with the use of immunosuppressive drugs. In this manuscript, the current status of clinical protocols for induction of tolerance is briefly discussed. Furthermore, the future of research in transplantation will involve basic scientists and clinical scholars working in concert as has been developed at Stanford School of Medicine with the creation of the Institute for Immunity, Transplantation and Infection. PMID- 20304206 TI - The future of liver transplantation. AB - Liver transplantation has been a positive impact on both the survival and the quality of life of patients with advanced liver diseases. Progressive, spectacular improvements in the results of liver transplantation have been observed since the preliminary studies by Thomas Starzl in the United States and Roy Calne in Europe. This improvement is related to better knowledge of the natural history of liver diseases, allowing more adequate recipient selection, improvement of surgical techniques, progress in postoperative management, availability of potent antibacterial, antiviral, and antifungal drugs, as well as introduction of new immunosuppressive agents and protocols. These advances have occurred in the short interval of 45 years, suggesting future improvements in the liver transplantation field. The main investigative efforts in liver transplantation have been directed as follows: First attenuation of disproprortion between the numbers of available liver grafts versus waiting list recipients, by increasing the donor pool applying bioartificial support systems, or rendering grafts compatible by the use of stem cells. Second, improved knowledge about the biology of primary liver tumors establishes indications for and optimal moments of transplantation. Third, application of individualized immunosuppressive protocols, adapted to clinical status of the recipient, as well as the development of more selective, less toxic new immunosuppressive agents. PMID- 20304207 TI - Liver transplantation for acute liver failure: a Spanish perspective. AB - The Spanish characteristics of organ donation (high accessibility to a transplant) and the different proportion in the etiologies of acute liver failure (ALF), namely, the very low incidence of paracetamol overdose causing this syndrome in contrast with other Western countries, are the causes of some specific features of emergency liver transplantation for ALF. The most relevant are the short time between the need for a graft and effective urgent liver transplant, and the high proportion of patients who undergo this therapy. This paper analyzes these characteristics and provides information about the use of biological and nonbiological extracorporeal liver support devices in acute liver failure, suggesting that these systems should be tested in countries with a long waiting times for urgent liver transplantation, or in patients with ALF and contraindications for transplantation. PMID- 20304208 TI - Exclusions and deaths on the liver transplant waiting list. AB - OBJECTIVE: To analyze the characteristiscs, evolution and survival of patients included on the waiting list (WL) for liver transplantation (OLT). PATIENTS AND METHODS: Between February 2002 and April 2009, 254 patients were included on WL to receive a first graft. Two hundred twenty-two patients (87.4%) were transplanted (group T); 7 (2.8%) died on the WL and 25 (9.8%) were excluded, namely, 13 (52%) due to improvement (group IE) and 12, for other reasons (group OE). Data collected prospectively were analyzed retrospectively. RESULTS: Indications for transplant were cirrhosis (58%), hepatocellular carcinoma (HCC; 29%) and other etiologies (13%.) Average time on the WL was 60.3 +/- 62.9 days. Significant differences were not observed among the groups with respect to age, gender, or indication for OLT. The probability for exclusion due to progression and/or death was not significantly greater among patients included for HCC than for other reasons (P = .6). Survivals at 1, 3, and 5 years after WL inclusion were 81.2%, 73.3%, and 68.6%, respectively, in the whole series; and 85,4%, 76,9%, and 71.7% in group T. All group OE patients died before the first year, while group IE showed a survival of 100%, 91.7% and 91.7% at 1, 3, and 5 years, respectively. Survival was not different between groups T and IE (P = .03), but was lower in group OE than in groups T or IE (P < .001). CONCLUSION: The list mortality rate in our series was low, probably in relation to the short waiting time. The rate of exclusion from WL was 10%. Patient with hepatocellular carcinoma were not at an increased risk of WL exclusion. Patients excluded due to improvement displayed excellent survivals during the 5 years following exclusion. PMID- 20304209 TI - Improving the waiting list by using 75-year-old donors for recipients with hepatocellular carcinoma. AB - The best treatment for hepatocellular carcinoma (HCC) associated with liver cirrhosis is liver transplantation and the best results are obtained when the tumors fulfill the Milan criteria. However, although the number of transplants is increasing, the organ deficit is growing, which lengthens time on the waiting list, increasing the risk of tumor progression of and exclusion from the list. The use of elderly donors is a valid option for patients on the transplant waiting list with HCC, reducing time on the waiting list. We report our experience with patients transplanted for HCC associated with hepatic cirrhosis using livers from donors >75 years of age. Our preliminary results supported the use of elderly suboptimal donors making it possible to give priority to these patients. All patients in the series achieved good graft function after a follow up of 2 years with a 100% disease-free survival rate. More extensive long-term studies are needed to confirm these findings. PMID- 20304210 TI - Early graft dysfunction after liver transplantation. AB - Liver transplantation has become the treatment of choice for fulminant hepatic failure and end-stage liver diseases. Several factors have been described to be predictors of graft function. Since early graft dysfunction dramatically influences graft and patient outcomes after liver transplantation, prevention of this event is mandatory. Donor-, procurement-, operative- and recipient-related factors influence the development of graft dysfunction. We have presented herein a review of the impact of these factors on graft dysfunction. PMID- 20304211 TI - Indications for and survival after liver retransplantation. AB - INTRODUCTION: Orthotopic liver retransplantation (re-OLT) is the therapeutic option for hepatic graft failures. Survival after re-OLT is poorer than after primary OLT. Given that there is an organ shortage, it is essential that we optimize our use of this scarce resource. We evaluated the results of re-OLT among 58 consecutive Re-OLT. MATERIALS AND METHODS: Using registry data from our Liver Transplantation Unit, we performed a retrospective cohort study of adult urgent versus elective re-OLT between 1991 and 2008. We recorded the indications for the initial OLT, and the intervals from OLT to re-OLT as well as age and gender. Using the Rosen model to stratify patients into low-intermediate-, and high-risk groups we calculated survivals. RESULTS: Among 661 adult liver transplantations, 56 patients (8.4%) underwent late re-OLT at a median of 654.4 days post-OLT. There were 17 (29%) urgent re-OLT and 41 elective cases (71%). Vascular complications were the most common cause of urgent re-OLT (64%); elective re-OLT was primarily due to chronic rejection (56.1%). Overall survival for retransplanted patients was significantly lower among urgent procedures (82.4% vs 48.8%), as well as for overall survival after re-OLT for patients with hepatitis C virus (HCV) versus other etiologies. CONCLUSION: These data confirmed the utility of retransplantation in elective and emergency situations. Liver re transplantation has a high morbidity and mortality. It requires multidisciplinary experience to decide inclusion and prioritization criteria for re-OLT, especially among patients with HCV. PMID- 20304212 TI - Rescue immunosuppression with mammalian target of rapamycin inhibitor drugs in liver transplantation. AB - BACKGROUND: Mammalian target of rapamycin (mTOR) inhibitors behave as potent immunosuppressants, which have the advantages, with respect to calcineurin inhibitors (CNI; cyclosporine or tacrolimus), of no nephrotoxicity but inhibition of cell proliferation. They are particularly suitable for patients with renal insufficiency or neoplasias. MATERIALS AND METHODS: Twenty-eight liver transplant patients were immunosuppressed with everolimus or sirolimus as rescue therapy after CNI treatment: 8 hepatocellular carcinomas; 7 de novo malignancies; 6 renal insufficiencies; 3 chronic rejections; 3 acute rejection episodes; and 1 epilepsy. RESULTS: There were 0% tumor recurrences, 50% improvements in 33% no change, and 17% worsening of renal function among cases of renal insufficiency; 0% improvement in cases of chronic rejection, and 33% improvement in acute rejection episodes. There was a 7% incidence of acute rejection episodes, but no kidney failure, gastrointestinal intolerance, hydrocarbon intolerance, hypertension, or arterial or venous thrombosis. Diarrhea occurred in 7%; hypercholesterolemi in 46% hypertriglyceridemia in 50% thrombocytopenia in 14%, leukopenia in 14%, and anemia in 39%. The 12% intercurrent infection rate included oral thrush in 11%. Lower limb edema occurred in 21%; 1 case displayed facial edema and 1, alopecia. CONCLUSIONS: mTOR inhibitors were safe immunosuppressive drugs whose side effects were controlled and easily managed. They have advantages with respect to CNI due to their slight effects on kidney function and lack of promotion of diabetes mellitus. Although their long-term effectiveness for control of neoplastic diseases is yet to be seen, they can be used safely in these patients with a low incidence of rejection. Their effectiveness to control steroid-resistant acute rejection episodes or renal insufficiency seems significant, but they are of doubtful benefit for chronic rejection. PMID- 20304213 TI - Outcomes of domino liver transplantation: a single institution's experience. AB - AIMS: Domino liver transplantation (DLT) is a strategy to increase the donor pool. Explanted liver from patients with familial amyloidotic polyneuropathy (FAP) are often used as domino grafts, because the liver is normal apart from the production of the mutated transthyretin variant. We present the outcomes for both donors and recipients of DLT. MATERIALS AND METHODS: Retrospective analysis of initial DLT for 16 consecutive adult patients performed between July 2004 and July 2009. All cases of FAP donor to grafts were removed preserving the cava vein with reconstruction of the hepatic veins, except the first and seventh cases, where in we removed the retrohepatic vena cava with the liver without venovenous bypass. The postoperative follow-up period for surviving DLT recipients at the end of September 2009 was 2-62 months (mean, 26). RESULTS: Two patients out of 8 FAP donors died due to pulmonary thromboembolism on the 31st postransplant day, or sepsis at 35 days namely, an overall survival of 75%. One patient out of 8 recipients died namely, an early portal thrombosis on the 22nd postransplant day) with a crude survival of 87.5% in the recipient group (P = no significant [NS]). Four grafts from 8 FAP donors were lost-2 deaths and 2 retransplants due to thrombotic events on the first and second postransplant day-with a crude survival of 50%. Two of 8 recipients lost their grafts: 1 death and 1 retransplantation for an acute Budd-Chiari syndrome on the first postransplant day with a crude survival of 75% in the recipient group (P = not significant [NS]). CONCLUSION: We believe that the FAP liver graft is an excellent option for selected patients. Special care must be taken with thrombotic events. PMID- 20304214 TI - Is liver transplantation without abdominal drainage safe? AB - This observational, analytical cohort consisted of 35 consecutive liver transplant (OLT) patients with no intra-abdominal drain and a control cohort of 35 subjects operated immediately before the former who had placement of an intra abdominal drain. We sought to assess the impact of abdominal drainage on the diagnosis and prevention of early postoperative complications: hemoperitoneum, reinterventions, biliary leaks, or percutaneous drainage. We assessed variables related to the recipient (age, indication, pretransplant ascites, body mass index, Model for End-Stage Liver Disease score and rejection), the donor (age, steatosis, ischemia time) and intra- and postoperative factors (surgery time, blood product use, and coagulopathy). The end point was defined as the need for a reintervention, paracentesis, appearance, and drainage of collections as well as lengths of hospital and intensive care unit (ICU) stays. The postoperative ICU and in-hospital stays were similar between groups (3.7 vs 3.9 days and 12 vs 14 days, respectively). Two patients in the group with drainage were reoperated due to hemoperitoneum, whereas we did not reoperate any patients in the group without drainage. No patient from either group developed a biliary fistula or required drainage of an intra-abdominal collections. The need for paracentesis was greater among the group without drainage (23% vs 5.7%; P < .04) and among those with a prior history of severe ascites. Patients with drainage displayed a greater incidence of perihepatic hematomas by ultrasound (53% vs 21%; P < .08) and required more postoperative blood products, especially platelets (P > .04) and plasma (P < .01). CONCLUSION: OLT without intra-abdominal drainage is safe, not increasing morbidity. It seems likely that drainage may be responsible for intra abdominal hematomas and greater consumption of blood products. PMID- 20304215 TI - Influence of mycophenolate mofetil on preservation of kidney function in liver transplant patients. AB - BACKGROUND: There are numerous studies on the effect of immunosuppressive therapy with mycophenolate mofetil (MMF) on preservation of kidney function in liver transplant (OLT) patients with chronic kidney damage. However, we have noted few studies that evaluate the role of this drug prescribed from induction on kidney function. PATIENTS AND METHODS: This prospective observational multicenter study included 296 OLT performed from 2005 to 2007. The collected variables were; gender, and age, Child-Pugh stage, Model for End-Stage Liver Disease (MELD) score, transplant indication, induction immunosuppressive therapy, and baseline and 1 year posttransplant values of creatinine and glomerular filtration rate. Patients were classified into 4 groups: group 1 received MMF from induction; group 2 was never treated with MMF; group 3 started MMF in the first month posttransplant, and group 4 started MMF therapy in the third month posttransplant. We used Wilcoxon and Mann-Whitney U statistical tests. RESULTS: There was a difference of 0.18 mg/dL in baseline creatinine values between groups 1 and 2 (P < .01). However, although patients who consistently had MMF in their treatment started with worse creatinine values, they were able to maintain them within normal ranges at 12 months. In contrast, patients in group 2 showed a significant worsening of 0.28 mg/dL in the first month that persisted throughout the study. Group 3 displayed worse baseline creatinine values than group 2 (P < .05), and also suffered an increase of 0.29 mg/dL (P < .01) versus baseline at 1 month. When MMF was added to their immunosuppressive therapy, the creatinine values reduced versus 1 month by 0.18 mg/dL (P < .05). Creatinine values remained stable at the other study assessments. Group 4 showed a normal creatinine value at baseline, but were altered at 1 and 3 months (P < .01), with increases versus baseline of 0.46 and 0.35 mg/dL, respectively. However, when MMF was introduced kidney function was restored and maintained over the study. CONCLUSION: Early introduction of MMF improved creatinine values among patients with impaired kidney function, maintaining them at stable levels. Furthermore, patients with altered creatinine values at baseline did not worsen their kidney function if they receive MMF from induction. PMID- 20304216 TI - Improvement of renal function after conversion to mycophenolate mofetil combined with low-level calcineurin inhibitor in liver transplant recipients with chronic renal dysfunction. AB - INTRODUCTION: Calcineurin inhibitors (CNI) are the main pathogenic factors for renal dysfunction in solid organ transplant recipients. Introduction of non nephrotoxic immunosuppressive drugs, such as mycophenolate mofetil (MMF), may allow discontinuation or reduction of CNI treatment, thereby improving renal function. The aim of this study was to assess the feasibility, efficacy and safety of MMF introduction and CNI dosage reduction in the maintenance immunosuppressive protocol to improve renal function in liver transplant recipients with chronic renal dysfunction. PATIENTS AND METHODS: We prospectively included 88 liver transplant recipients including 74 men and an overall mean age of 58.8 +/- 10.3 years who all displayed chronic renal dysfunction (creatinine >1.4 mg/dL) and proteinuria <1 g/d. They were subdivided into 3 groups according to the basal creatinine value 1.4-1.7 mg/dL (group I; n = 41); 1.8-2.0 mg/dL (group II; n = 28); and >2 mg/dL (group III; n = 19). MMF was initiated at 1.5 2.0 g/d. Reduction of tacrolimus or cyclosporine dosage was performed to achieve respective target trough levels of <5 ng/mL or <50 ng/mL. We performed periodic determinations of arterial pressure, liver function tests, serum creatinine, blood cells count, CNI levels, and proteinuria. RESULTS: Creatinine values after conversion were 1.4 +/- 0.5 mg/dL in the overall group. Improvement of renal function was more frequent among groups I (80.4%) and II (92.8%) versus III (73.6%). Normalization of creatinine values was more frequent in group I (68.2%) with respect to cohorts II (21.4%) and III (10.5%). Rejection was not detected. CONCLUSION: Application of an immunosuppressive protocol with MMF and low-level CNI in liver transplant recipients with chronic renal dysfunction was associated with improvement or normalization of creatinine, without an increased risk of rejection. Early conversion is needed to achieve the best results. PMID- 20304217 TI - Management of hepatocellular carcinoma recurrence after liver transplantation. AB - Management of patients with hepatocellular carcinoma (HCC) recurrence after liver transplantation (OLT) is not well established. We conducted a retrospective analysis of our results in the treatment of HCC recurrence after OLT Patients. The 23 HCC recurrences developed after 182 OLT performed for HCC within Milan criteria, had an average follow-up of 60 months. RESULTS: The median time to recurrence was 23.4 months. Surgical resection of the recurrence was possible in 11 patients, but an R-0 resection was obtained in 8 patients. Four of these 8 patients developed another recurrence, with 3 succumbing due to tumor recurrence and 1 alive at 12 months with recurrence. The other 4 patients without recurrences, include 3 who are alive at 19, 31, and 86 months and 1 who died at 32.6 months due to hepatitis C recurrence. The 3 patients with palliative resections developed recurrences. Twelve patients were rejected for surgery: 8 were treated symptomatically, 2 with systemic chemotherapy, and 2 with everolimus and sorafenib. This last treatment was also prescribed for 2 patients after R-0 surgery who are alive at 19 and 31 months and for 1 patient after R-1 surgery who is alive at 19 months. Of 15 patients who died, 13 succumbed to HCC recurrence. The average survival from transplantation was 61.7 +/- 37.5 and 48 +/- 34.3 months for patients without and with recurrence, respectively (P < .001). The survival from the recurrence was significantly higher among patients with R-0 surgery: 32.3 +/- 21.5 versus 11.9 +/- 6.9 months (P = .006). CONCLUSIONS: HCC recurrence after OLT of patients within Milan criteria was low but had a great impact on survival. Few cases are amenable to R-0 resection, but when possible it was associated with a significantly increased survival, although with an high incidence of a new recurrence. There is a rationale for the use of sorafenib and mammalian target of rapamycin based immunosuppression, which warrants randomized studies. PMID- 20304218 TI - Risk of development of the metabolic syndrome after orthotopic liver transplantation. AB - Longer survival for orthotopic liver transplantation (OLT) patients over the last decade has focused emphasis on the metabolic complications that contribute to patient morbidity and mortality. The aim of our study was to analyze the prevalence of the metabolic syndrome (MS) and other risk factors after OLT among our patients at 1 year follow-up. From 2001 to 2008, we performed OLT in 210 patients with 62 exclusions leaving 148 patients for the study. We recorded age, gender, liver disease, smoking status, pre- and post-OLT body mass index, pre- and post-OLT arterial blood pressure, pre- and post-OLT fasting blood glucose, pre- and post-OLT high-density lipoproteins and triglycerides, family history of diabetes, hepatitis B and C virus status, immunosuppressive therapy, and corticosteroid bolus for rejection episodes. The MS was defined according to modified ATP III criteria. At month 12 after OLT, 29/148 patients (19.6%) developed the MS. The associated factors were obesity and hyperlipidemia pre-OLT, familial and personal history of diabetes as well as alcoholic cirrhosis. By multivariate analysis, pre-OLT body mass index (odds ratio, 3.7 [1.3-10.5]) and pre-OLT diabetes (odds ratio, 2.9 [1.1-7.9]) were independent risk factors. PMID- 20304219 TI - Hepatitis C virus recurrence after liver transplantation: analysis of factors related to sustained viral response. AB - OBJECTIVES: To determine the efficacy and safety of pegylated interferon (peg IFN) plus ribavirin to treat hepatitis C virus (HCV) recurrence, analyzing possible factors associated with sustained viral responses (SVR). PATIENTS AND METHODS: Forty-one patients (25 men and 16 women) of overall mean age of 50 years (range, 33-60) with recurrent HCV were treated with peg-IFN plus ribavirin including 33 (80%) subjects displayed genotype 1. The following variables were analyzed: gender, donor and recipient ages, immunosuppressant, genotype, treatment duration, early viral response (EVR), pretreatment viral load, degree of fibrosis, levels of alanine aminotransferase and gamma-glutamyltransferase (IU/L), time since liver transplantation (OLT), use of stimulating factors (epoetin and granulocyte colony stimulating factor [G-CSF]) and side effects, and their association with SVR. The time from OLT to the start of treatment was 29 months (range, 6-90). Seventy-one percent of patients received cyclosporine and 29% tacrolimus. RESULTS: The mean treatment duration was 31 (range, 4-72) months with an EVR achieved in 12/38 (31.5%) of patients and a SVR in 16/41 (39%). Treatment was discontinued in 23 patients due to side effects. Epoetin was necessary in 29% and G-CSF in 10%. There were 3 cases of rejection (1 mild and 2 severe culminating in death). On univariate analysis genotype non-1B (P < .02), pretherapy RNA (P < .02), complete treatment, and EVR (P < .005) were the only variables associated with SVR. The mean donor age of 43 years showed no statistical significance. CONCLUSION: Therapy with peg-IFN plus ribavirin achieves an acceptable SVR, although not entirely free from severe side effects. Ensuring completion of the full treatment course is fundamental to achieve SVR. PMID- 20304220 TI - In vitro evaluation of new possible cell engraftment enhancers for cell transplantation. AB - Orthotopic liver transplantation (OLT) is the best treatment to restore liver function in liver failure. The low availability of organs has focused interest on the use of cell transplantation to restore liver function. However, this technique is limited because cells can not bind to liver parenchyma and die soon after perfusion. Pretransplant treatment with engraftment enhancers (EE) to increase vascular permeability may increase cell attachment. Using an endothelial cell culture to measure the loss of intercellular endothelial adhesion as a screening test, we evaluated the capacity of 15 monoclonal antibodies against adhesion molecules expressed on endothelial cells to act as EE showing that 3 antibodies (anti-CD54, efalizumab, and abciximab) act as EE by producing disruptions in the cell layer. PMID- 20304221 TI - Pathology and epidemiology of HPV infection in females. AB - Human papillomaviruses (HPVs) are a large family of small double-stranded DNA viruses that infect squamous epithelia. It has been established that infection with specific HPV types is a contributing factor to different types of anogenital cancer, including vulval, vaginal, anal, penile, and head and neck cancers. Approximately 4% of all cancers are associated with HPV. HPV infection is the major cause of cervical cancer and genital warts. Genital HPV infections are very common, are sexually transmitted, and have a peak prevalence between ages 18 and 30. Most of these infections clear spontaneously, but in 10-20% of women, these infections remain persistent and are at risk of progression to grade 2/3 cervical intraepithelial neoplasm (CIN) and eventually to invasive cancer of the cervix (ICC). CINs are genetically unstable lesions with a 30-40% risk of progression to ICC. If left untreated, they form a spectrum of increasing cytological atypia, ranging from low-grade CIN1 to high-grade CIN3; the latter are caused almost exclusively by high-risk HPVs, HPV 16 and 18. Infection with HPV requires a microabrasion in the genital epithelium. The oncogenic properties of high-risk HPV reside in the E6 and E7 genes, which if inappropriately expressed in dividing cells deregulate cell division and differentiation. HPV DNA testing has been shown consistently to be superior to cytology in terms of sensitivity and positive predictive value and will become a major tool in cervical cancer screening, at least in the developed countries. PMID- 20304222 TI - DFID: a report card and a reappraisal. PMID- 20304223 TI - Caesarean section-the first cut isn't the deepest. PMID- 20304224 TI - Another step towards preventing artemisinin resistance. PMID- 20304225 TI - Carotid stenting: more risky than endarterectomy and often no better than medical treatment alone. PMID- 20304226 TI - Gardasil: from bench, to bedside, to blunder. PMID- 20304227 TI - A tale of two-component generalised HIV epidemics. PMID- 20304230 TI - Offline: Life in the senior common room. PMID- 20304232 TI - Degeneration. PMID- 20304233 TI - DART and laboratory monitoring of HIV treatment. PMID- 20304235 TI - DART and laboratory monitoring of HIV treatment. PMID- 20304236 TI - Mexico's conditional cash transfer programme. PMID- 20304238 TI - Diabetes in Asia. PMID- 20304239 TI - Registering observational research: second thoughts. PMID- 20304240 TI - Health-care needs of people affected by conflict. PMID- 20304241 TI - Diabetes in Asia. PMID- 20304242 TI - Adjustment of dosing of antimicrobial agents for bodyweight in adults. PMID- 20304243 TI - Scaling up financing for health. PMID- 20304244 TI - Online journals: paying or delaying? PMID- 20304245 TI - Comparative demographics of the European cystic fibrosis population: a cross sectional database analysis. AB - BACKGROUND: Country-specific patients' registries are rarely used to make international comparisons because of protocol discrepancies in data collation. We present data from a European cystic fibrosis registry that is dedicated to collection of demographic data, and assess whether the resources available in countries with and without European Union (EU) membership affects care and survival of patients. METHODS: Data for demographic indicators-age, age at diagnosis, sex, and genotype-for patients with cystic fibrosis from 35 European countries were combined, and used to establish the differences in demographic indicators between EU and non-EU countries. EU membership status in 2003 was used to divide countries. We modelled demographic indicators of EU countries on non-EU countries to estimate the size of the cystic fibrosis population if non-EU countries had had the same resources available for patients as did EU countries. FINDINGS: Data were gathered for 29 025 patients, who had a median age of 16.3 years (IQR 8.9-24.8), with a difference of 4.9 years (95% CI 4.4-5.1; p<0.0001) between EU (median 17.0 years, IQR 9.5-25.6) and non-EU countries (12.1 years, 6.0-19.2). The proportion of patients older than 40 years was higher in EU countries (1205 [5%]) than in non-EU countries (76 [2%]), with an odds ratio of 2.4 (95% CI 1.9-3.0, p<0.0001). We estimated that the cystic fibrosis population in non-EU countries would increase by 84% if patients had a demographic profile comparable to that of patients in EU countries. INTERPRETATION: Future studies need to establish the reasons for the lower proportion of patients with cystic fibrosis in non-EU countries than in EU countries, such as underdiagnosis and premature childhood mortality. FUNDING: European Community's Sixth Framework Programme for Research, and Czech Ministry of Health. PMID- 20304246 TI - A retrocaval ureter. PMID- 20304247 TI - Colorectal cancer. AB - Substantial progress has been made in colorectal cancer in the past decade. Screening, used to identify individuals at an early stage, has improved outcome. There is greater understanding of the genetic basis of inherited colorectal cancer and identification of patients at risk. Optimisation of surgery for patients with localised disease has had a major effect on survival at 5 years and 10 years. For rectal cancer, identification of patients at greatest risk of local failure is important in the selection of patients for preoperative chemoradiation, a strategy proven to improve outcomes in these patients. Stringent postoperative follow-up helps the early identification of potentially radically treatable oligometastatic disease and improves long-term survival. Treatment with adjuvant fluoropyrimidine for colon and rectal cancers further improves survival, more so in stage III than in stage II disease, and oxaliplatin based combination chemotherapy is now routinely used for stage III disease, although efficacy must be carefully balanced against toxicity. In stage II disease, molecular markers such as microsatellite instability might help select patients for treatment. The integration of targeted treatments with conventional cytotoxic drugs has expanded the treatment of metastatic disease resulting in incremental survival gains. However, biomarker development is essential to aid selection of patients likely to respond to therapy, thereby rationalising treatments and improving outcomes. PMID- 20304248 TI - Wiring a nation: putting knowledge into action. PMID- 20304249 TI - Nosocomial transmission of necrotising fasciitis. PMID- 20304250 TI - The perennial threat of influenza pandemics. PMID- 20304251 TI - Molecular anatomy of 2009 influenza virus A (H1N1). AB - Influenza A viruses are a major cause of morbidity and mortality worldwide and affect large segments of the population every year. The nature of their genome, formed by eight segments of single-stranded RNA, favors the constant evolution of the virus by two main mechanisms: the accumulation of single nucleotide mutations in the viral genes introduced by an error-prone viral RNA polymerase and the reassortment of genes between two strains of different origin. The viral genome encodes 11 proteins. Most have been shown to play a role in shaping the virulence scenario of influenza A viruses, including the adaptation of infection and transmission into new host species, the ability to modulate the host immune response, and the capacity to replicate efficiently at low temperature. On the surface of the virus particles there are two principal polypeptides, the hemagglutinin (HA) and the neuraminidase (NA), which are the target for the neutralizing antibodies immune response. There are 16 HA and 9 NA different subtypes in the influenza A virus that circulate in humans and animals. When a virus strain with a new HA or NA subtype appears in the human population by genetic reassortment, it usually causes a pandemic because there is no preexisting immunity against the new virus. This was the case for the three pandemics that occurred during the last century (1918, 1957, and 1968) and also for the first pandemic of the 21(st) century, caused by the currently circulating A (H1N1) 2009 virus, which was generated by gene reassortment between a virus present in pigs of North America and a virus that circulates in the swine population of Euroasia. PMID- 20304252 TI - Comparison of the pathology caused by H1N1, H5N1, and H3N2 influenza viruses. AB - The spectrum of morbidity and mortality of H1N1, H5N1, and H3N2 influenza A viruses relates to the pathology they produce. In this review, we describe and compare the pathology of these viruses in human cases and animal models. The 1918 H1N1, the novel 2009 H1N1 pandemic virus, and H5N1 show inflammation, congestion, and epithelial necrosis of the larger airways (trachea, bronchi and bronchioles) with extension into the alveoli causing diffuse alveolar damage. Seasonal influenza A viruses (H3N2 and H1N1) have primarily caused inflammation, congestion and epithelial necrosis of the larger airways with lesser extension of the inflammatory process to alveoli. Localization of the inflammation and cellular damage relate to the presence of virus in different cell types. Infections with 1918 H1N1, the novel 2009 H1N1 pandemic virus, and H5N1 show virus in mucosal epithelial cells of the airways (from the nasopharynx to the bronchioles), alveolar macrophages, and pneumocytes, whereas infections with seasonal influenza viruses show viral antigens primarily in mucosal epithelial cells of the larger airways. The increased morbidity that has been encountered with the 2009 H1N1 virus is related to infection of cells in the upper and lower airways. The 2009 H1N1 virus shows similar pathology to that encountered with other highly virulent influenza A viruses such as the 1918 H1N1 and H5N1 viruses. PMID- 20304253 TI - Critical analysis of deaths due to atypical pneumonia during the onset of the influenza A (H1N1) virus epidemic. AB - BACKGROUND: The ongoing influenza A (H1N1) pandemic stroked Mexico and posed a huge challenge to the medical care and public health systems. This report analyzes the clinical course and process of care of patients who died due to atypical pneumonia and fulfilled the clinical criteria of suspected case of novel influenza A (H1N1) virus infection. METHODS: We conducted a retrospective analysis of a series of 38 patients who died between April 7 and April 28, 2009 at Instituto Mexicano del Seguro Social (IMSS) hospitals due to severe pneumonia and respiratory distress. These cases coincided with the beginning of the outbreak, so patients did not undergo laboratory testing to diagnose influenza. According to IMSS and CDC criteria, post-hoc analysis allowed considering the presumptive diagnosis of S-OIV infection. A multidisciplinary group analyzed the information from the clinical charts, laboratory tests, radiographic studies and death certificates, using descriptive statistics. RESULTS: Most cases were middle aged (mean 33 years, range: 4-62 years) and previously healthy; 18.4% had an underlying chronic disease, 23.7% were obese and 7.9% were current smokers. None had received the seasonal influenza vaccine; they had cough (92%), fever (86.8%), and malaise (73.7%). The median time from disease onset to hospital admission was 6 days (range 0-8 days). All were admitted to the intensive care unit with pneumonia and/or respiratory distress. Average time from disease onset to death was 8 days (range 4-18 days). CONCLUSIONS: An increased number of severe cases of atypical pneumonia in previously healthy adults highlight the importance of the availability of a timely surveillance system able to identify sudden increases in the number of cases or presentation of apparently known diseases. PMID- 20304254 TI - H1N1 influenza pandemics: comparing the events of 2009 in Mexico with those of 1976 and 1918-1919. AB - Outbreaks of influenza A (H1N1) of avian- or swine-related origin have substantially impacted human populations. The most dramatic pandemic of influenza H1N1 occurred during 1918-1919 producing significant morbidity and mortality worldwide. In the 20th century, two other major pandemics took place but they were the H2N2 and H3N2 reassorted influenza strains. In 1976, a small outbreak of swine-related H1N1 in the U.S. led to a national scare but without any significant public health impact. More recently, in April 2009, in Mexico, and subsequently worldwide, an influenza (H1N1) triple reassortant strain produced >200,000 laboratory-confirmed cases and resulted in >2000 deaths. In August 2009, WHO declared this outbreak as the first influenza pandemic of the 21(st) century. It is critical to apply lessons learned during previous pandemics to mitigate the public health impact of the ongoing influenza pandemic in 2009. In particular, it is useful to compare the events in Mexico in 2009 to those during the Spanish influenza pandemic of 1918-1919. PMID- 20304255 TI - What have we learned from the novel influenza A (H1N1) pandemic in 2009 for strengthening pandemic influenza preparedness? AB - We need to apply lessons learned from previous influenza pandemics to continuously update preparedness and response plans. It has become evident that strengthening networks of international referral laboratories coupled with scaling-up efforts to expand epidemiological surveillance networks is critical for responding and mitigating the impact of influenza pandemics. The current swine-related influenza A (H1N1) pandemic has also shown that international collaboration remains a critical component to effectively respond to influenza pandemics in the current globalized world. PMID- 20304256 TI - Lessons from previous influenza pandemics and from the Mexican response to the current influenza pandemic. AB - Better understanding of the events occurring during prior influenza pandemics, particularly the 1918 pandemic, and the realization that another pandemic was inevitable and likely to occur early in the 21(st) century, have helped in preparedness planning. In Mexico, pandemic flu preparedness was critical and undoubtedly paid off once a new influenza pandemic was identified in April 2009, but it also became apparent that these plans required flexibility and significant adjustments as the epidemic evolved. We review here the lessons learned in Mexico from the current influenza pandemic. In addition, we highlight various issues that should be addressed among countries and by the international community before the next influenza pandemic occurs. There have been many lessons learned but the one we cannot forget is that complacency is dangerous and not acceptable when confronting the threat of an influenza pandemic. PMID- 20304257 TI - Organization of a third-level care hospital in Mexico City during the 2009 influenza epidemic. AB - An outbreak caused by the novel swine-origin influenza A (H1N1) virus was identified in Mexico in late March 2009. The objective of this report is to describe the organization of a tertiary care center in Mexico City during the contingency. We describe the education program, the hospital organization and triaging, and unforeseen overwhelming circumstances. Educational plans were directed to follow standard, contact, and droplet precautions and to condition behavior to avoid touching the eyes, nose, or mouth. N95 respirators were distributed only to perform respiratory procedures. By the fifth month into the epidemic, four patients with hospital-acquired influenza, 467 workers with respiratory symptoms suggestive of influenza (16% of our staff), and 96 workers with confirmed novel influenza A (3% of our staff) were identified. During the first 2 months of the epidemic, 44,225 people went through the triages and only 1503 (3.3%) reached the emergency room. By the fifth month into the epidemic, four small institutional influenza outbreaks (<10 workers each) had been identified, two of them in areas with no patient contact. Molecular testing for influenza was used mainly for epidemiological purposes. Even though we had a supply, we had difficulties in meeting the demand of masks, N-95 respirators, and hand sanitizers. Due to absenteeism, the nursing administration experienced difficulties in covering shifts. Preparation is mandatory for facing an influenza epidemic. The correct use of precautions is an economic measure to limit institutional transmission. Adequate triaging is essential to meet unusual attention demands. PMID- 20304258 TI - Identification of seasonal vaccine hemagglutinin subtype 1 (H1) epitopes in Mexican isolates of the new influenza A (H1N1) 2009 virus. AB - BACKGROUND: Pre-existing immunity in individuals is a determinant condition for epidemic dynamics. During the current influenza A (H1N1) virus pandemic, cross reactivity of seasonal vaccines from the last years and previous contact with seasonal influenza viruses was suggested as the cause of low severity and low incidence of the disease in persons aged 50-65 years and with history of seasonal influenza vaccination. METHODS: We performed a detailed search and analysis of 74 previously reported H1 epitopes present in influenza A virus contained in seasonal vaccines applied in Mexico from 2004 to date and in sequences from Mexican isolates from 2003, as well as in the recent influenza A (H1N1) 2009, and calculated the epitope conservation among vaccine, seasonal and pandemic influenza A (H1N1) virus. RESULTS: H1 epitope sequence identity ranged from 61.53 100 %. Of the 74 epitopes previously reported, 31 (41.9%) were completely conserved among all sequences analyzed in this study, whereas 43 (58.1%) had changes in one or more amino acids. CONCLUSIONS: Our findings contribute to the estimatation of the degree of epitope conservation among H1 from vaccine virus strains as well as in the different viruses that circulate in the Mexican population. These results may provide new elements to consider for analysis of cross-immunity to influenza viruses including the novel influenza A (H1N1) 2009 pandemic virus. PMID- 20304259 TI - Vaccines against influenza A (H1N1) pandemic. AB - BACKGROUND AND AIMS: The World Health Organization (WHO) has reported, as of September 2009, that the influenza A (H1N1) influenza pandemic has originated >300,000 laboratory-confirmed cases and 3917 deaths in 191 countries. It is recognized that pandemic vaccines have their greatest impact as a preventive strategy when administered before or near the peak incidence of cases in an outbreak. Therefore, vaccination campaigns should be in place when influenza A (H1N1) 2009 vaccines are available. We undertook this study to provide updated information on clinical evaluation of influenza A (H1N1) vaccines and review recommendations for influenza A (H1N1) vaccination campaigns and public health policy. METHODS: The following methods were used: 1) review of registry at ClinicalTrials.gov. 2) search of PubMed Central (PMC) for influenza A (H1N1) vaccine. 3) review of recommendations of WHO, Mexican Health Secretariat (SSA) and Advisory Committee on Immunization Practices (ACIP) on influenza A (H1N1) vaccination campaigns. RESULTS: Until October 1, 2009 there were 11 available influenza A (H1N1) candidate strains provided by WHO Global Influenza Surveillance Network. ClinicalTrials.gov registers 45 phase I and II clinical trials evaluating immunogenicity and safety of influenza A (H1N1) vaccines. Preliminary results support administration of a single dose and use of adjuvants. Main recommendations of WHO, SSA and ACIP include epidemiologic considerations, objectives, definition of target groups and reinforcement of other mitigation measures. CONCLUSIONS: The present pandemic of influenza A (H1N1) has shown mild to moderate severity. Vaccination strategies in Mexico will have the objective of decreasing severe outcomes, slowing transmission, protecting groups at increased risk of infection, complications, or death, and preventing overload of health services. Control of the pandemic should include reinforcement of other non pharmacologic measures of mitigation and, importantly, an adequate strategy of social communication. PMID- 20304262 TI - Cases. PMID- 20304260 TI - Acceptance of a vaccine against novel influenza A (H1N1) virus among health care workers in two major cities in Mexico. AB - BACKGROUND AND AIMS: Further cases of novel influenza A (H1N1) outbreak are expected in the coming months. Vaccination has been proven to be essential to control a pandemic of influenza; therefore, considerable efforts and resources have been devoted to develop a vaccine against the influenza A (H1N1) virus. With the current availability of the vaccine, it will be important to immunize as many people as possible. However, previous data with seasonal influenza vaccines have shown that there are multiple barriers related to perceptions and attitudes of the population that influence vaccine use. The aim of the study was to evaluate the acceptance of a newly developed vaccine against pandemic (H1N1) 2009 influenza A among healthcare workers (HCW) in Mexico. METHODS: We conducted a cross-sectional study among HCW in three hospitals in the two largest cities in Mexico-Mexico City and Guadalajara-between June and September 2009. RESULTS: A total of 1097 HCW participated in the survey. Overall, 80% (n = 880) intended to accept the H1N1 pandemic vaccine and 71.6% (n = 786) reported they would recommend the vaccine to their patients. Doctors were more likely to accept and recommend the vaccine than nurses. HCWs who intend to be immunized will be more likely to do so if they know that the vaccine is safe and effective. CONCLUSIONS: Knowledge of the willingness to accept the vaccine can be used to plan strategies that will effectively respond to the needs of the population studied, reducing the health and economic impact of novel influenza A (H1N1) virus. PMID- 20304263 TI - Extracts from The Cochrane Library: Scopolamine (hyoscine) for preventing and treating motion sickness. PMID- 20304264 TI - How to review journal manuscripts. AB - Reviewing manuscripts is central to editorial peer review, which arose in the early 1900s in response to the editor's need for expert advice to help select quality articles from numerous submissions. Most reviewers learn by trial and error, often giving up along the way because the process is far from intuitive. This primer will help minimize errors and maximize enjoyment in reviewing. Topics covered include responding to a review invitation, crafting comments to editors and authors, offering a recommended disposition, dealing with revised manuscripts, and understanding roles and responsibilities. The target audience is primarily novice reviewers, but seasoned reviewers should also find useful pearls to assist their efforts. PMID- 20304265 TI - Mentoring in otolaryngology training programs. AB - OBJECTIVE: The Accreditation Council for Graduate Medical Education's focus on outcome-based training has made the mentoring process critical for resident education. It is unknown how otolaryngology training programs mentor residents. Our objective was to determine the current state of mentoring in otolaryngology training programs and describe resident perceptions of mentoring. STUDY DESIGN: Cross-sectional survey. SETTING: Accredited U.S. otolaryngology training programs. SUBJECTS AND METHODS: All U.S. otolaryngology residents and program directors were contacted via e-mail with a link to an online survey. RESULTS: Of the 1411 residents contacted, 27.7 percent responded, representing 71 of the 103 accredited otolaryngology programs. Of the 103 program directors contacted, 37.9 percent responded. Of these programs, 26 had formal mentoring programs, 45 did not have formal mentoring programs, and 12 programs were listed in both categories. Fifty-one percent of male residents and 49 percent of female residents had mentors. The most important mentor characteristics were personality match, good clinical role model, and similar subspecialty interests. Least important characteristics were race, gender, and age. Twenty-six percent of residents felt that mentoring was critical to their training, while 63 percent of residents listed mentoring as important but not critical. Programs with fewer faculty and residents were less likely to offer formal mentoring (P = 0.007 and 0.054, respectively). Of residents who did not have mentors, 80 percent lacked a mentor because their residency had no formal mentoring program. CONCLUSION: Residents perceive mentoring as important, and formal mentoring programs should be incorporated into otolaryngology training programs. PMID- 20304266 TI - Validation of a clinical practice ability instrument for surgical training. AB - OBJECTIVE: To develop and validate an instrument to measure the progression of clinical practice ability among surgical trainees. STUDY DESIGN: Prospective validation study. SETTING: Three academic training institutions: Massachusetts Eye and Ear Infirmary, Brigham and Women's Hospital, Harvard School of Public Health. SUBJECTS AND METHODS: A clinical practice instrument (CPI) was created and prospectively validated in otolaryngology trainees at three institutional sites. The instrument is completed during an oral examination of a trainee who is presented with a patient scenario; the scenario yields one clinical diagnosis, one therapeutic intervention, and one interventional complication. On the basis of the trainee's responses, 21 item scores are calculated focusing on key areas within the diagnostic and management paradigm. Internal consistency, reproducibility, inter-rater reliability, discriminant and criterion validity, and responsiveness to change over time were evaluated. RESULTS: There were 87 administrations of the instrument over a period of 22 months. The subjects (n = 32) spanned the range of training from medical student to clinical fellow. There was strong internal consistency within each domain (Cronbach's alpha 0.85-0.94, one-sided 95% confidence interval > 0.81). Inter-rater reliability was high (kappa 0.66, absolute agreement 72%). Reproducibility of item scores was excellent (intraclass correlation coefficient [ICC] final summary score 0.78, global item score 0.83). Discriminant validity (P < 0.0001), criterion validity (P = 0.03), and responsiveness to change (P = 0.0055) were also established. CONCLUSION: The CPI serves as a reliable, reproducible, and valid means to measure the progression of clinical practice ability in trainees as they transition from "novice" to "attending equivalent" surgeons. PMID- 20304267 TI - Complications of esophagoscopy in an academic training program. AB - OBJECTIVE: To assess the efficacy and safety of flexible versus rigid esophagoscopy in an academic training setting. STUDY DESIGN: Case series with chart review. SETTING: Tertiary academic training center. SUBJECTS AND METHODS: A retrospective medical record review was performed on all adult patients undergoing esophagoscopy from 2002 to 2007. RESULTS: A total of 546 procedures were performed with flexible (n = 276) or rigid (n = 270) endoscopes. Seven esophageal perforations (2.6%) occurred, all in association with rigid endoscopy and all in patients with a history of head and neck cancer. Esophageal perforation rates were associated with attending level of experience. There were no deaths. No synchronous esophageal cancers were found in any patient undergoing panendoscopy for the evaluation of a head and neck cancer. CONCLUSION: The 2.6 percent esophageal perforation rate observed in this study is higher than that typically reported for rigid esophagoscopy. When performed as part of routine panendoscopy, no synchronous esophageal tumors were found, questioning the value of esophagoscopy in this setting. All perforations occurred in patients with a history of head and neck cancer and were associated with the level of the surgeon's experience in performing rigid endoscopy. PMID- 20304268 TI - Effects of traditional Chinese acupuncture in post-viral olfactory dysfunction. AB - OBJECTIVE: To date, recovery of olfactory function after viral infection of the upper airway cannot be achieved reliably with pharmacotherapy. The aim of this study was to evaluate the effects of traditional Chinese acupuncture (TCA) on olfactory function in patients with persistent post-viral olfactory dysfunction (PVOD). STUDY DESIGN: Historical cohort study. SETTING: University Medical Center, Department of Otorhinolaryngology. SUBJECTS AND METHODS: A total of 15 patients presenting to the outpatient clinic with PVOD were treated by TCA in 10 weekly, 30-minute sessions. Subjective olfactometry was performed with the Sniffin' Sticks test set. Treatment success was defined as an increase in Sniffin' Sticks test scores of at least six points. The effects of TCA, obtained with the chi(2) test, were compared with those of matched pairs suffering from PVOD who had been treated with vitamin B complex over 12 weeks. RESULTS: Eight patients treated with TCA had improved olfactory function compared with two treated with vitamin B complex. chi(2) test revealed a significantly better outcome in olfactory function in patients undergoing acupuncture compared with patients receiving vitamin B complex (P = 0.02). CONCLUSION: TCA possibly offers a new therapeutic regimen for post-viral dysosmia. More research in a larger case series is needed before a clearer picture will emerge. PMID- 20304269 TI - Matrix metalloproteinase inhibition causes luminal narrowing and ring thickening in the cricoid cartilage. AB - OBJECTIVE: Luminal expansion of the cricoid cartilage appears to be stunted by loss of luminal epithelium (LE) and can be enhanced by transforming growth factor beta3 (TGF-beta3). When both the LE and perichondrium are disrupted, matrix metalloproteinase (MMP) levels within adjacent chondrocytes are diminished but can be restored by exogenous TGF-beta3. Cricoid growth stunting and luminal expansion that occur in the absence and presence of MMP activity, respectively, suggest that MMPs play an important role in normal subglottal development. The study objective was to determine if MMP inhibition affects cricoid expansion and by what mechanism, which will in turn help to define the mechanism of action of TGF-beta3-induced luminal expansion. STUDY DESIGN: Ex vivo, in vitro whole organ culture of subglottises grown with and without the presence of an MMP inhibitor. SETTING: Tertiary care facility. SUBJECTS AND METHODS: Subglottises from 20 neonatal mice were divided into 10 grown with an MMP inhibitor, GM6001, and 10 grown in basic medium alone. The luminal cross-sectional area, apoptosis levels, cell proliferation rates, and presence or absence of cleaved aggrecan fragments were determined. RESULTS: Subglottises that were exposed to the MMP inhibitor displayed statistically significant luminal narrowing, accompanied by apparent circumferential thickening of the cricoid ring, relatively decreased apoptosis, increased chondrocyte proliferation, and decreased amounts of aggrecan cleavage fragments in the extracellular matrix. CONCLUSION: Matrix metalloproteinases likely play a significant role in growth of the cricoid cartilage such that their inhibition leads to marked changes in the shape of the ring. PMID- 20304270 TI - Palatine tonsil size in obese, overweight, and normal-weight children with sleep disordered breathing. AB - OBJECTIVE: To assess palatine tonsil size relative to degree of obesity in children with sleep-disordered breathing (SDB). STUDY DESIGN: Case-control study. SETTING: Tertiary care rhinology clinic. SUBJECTS AND METHODS: We compared the subjective and objective tonsil size, including tonsil height (TH), tonsil width (TW), tonsil thickness (TT), tonsil weight (TWt), and tonsil volume (TV), in 26 obese children and 26 age- and gender-matched control children with SDB, and in 29 overweight children and 29 matched controls with SDB. RESULTS: Despite similar subjective tonsil size in obese and control children, the objective tonsil size, including TH, TW, TT, and TWt, was larger in obese than in control children, and the mean TV was significantly greater in obese than in control children with SDB (8.53 +/- 3.30 mL vs 6.90 +/- 2.05 mL; 95% confidence interval [CI] of the difference 0.03-3.25; P = 0.019). In contrast, mean TV (7.38 +/- 3.43 mL vs 7.65 +/- 1.97 mL; 95% CI -1.92 to 1.37; P = 0.320) as well as the other parameters of objective palatine tonsil size, including TH, TW, TT, and TWt, did not differ significantly between overweight children and controls. CONCLUSION: Obese children with SDB had larger palatine tonsils than did normal-weight children with SDB. This finding suggests that larger palatine tonsils may have a greater effect on upper airway obstruction in obese than in normal-weight children with SDB. PMID- 20304271 TI - Measurements of adult lingual tonsil tissue in health and disease. AB - OBJECTIVES: To report computed tomography (CT) measurements of lingual tonsil tissue (LTT) in patients with laryngopharyngeal reflux (LPR), obstructive sleep apnea-hypopnea syndrome (OSAHS), both LPR and OSAHS, or neither disease. STUDY DESIGN: Retrospective chart review. SETTING: Tertiary care center. SUBJECTS AND METHODS: Ninety-eight patients with CT scans including the tongue base and complete historical data regarding the presence or absence of symptoms, signs, and laboratory confirmation of LPR and/or OSAHS were included. LTT was measured on CT. Charts of patients meeting inclusion criteria were subsequently reviewed and patients were divided into four groups: 1) those without LPR or OSAHS, 2) those with LPR only, 3) those with OSAHS only, and 4) those with both LPR and OSAHS. Statistical analysis focused on correlating LTT thickness with the presence or absence of LPR and/or OSAHS. RESULTS: The mean LTT thickness for group 1 (21 patients without reflux or OSAHS) was 0.937 mm (range 0-2.67 mm). The mean for group 2 (29 patients with LPR only) was 3.35 mm (range 0-7.4 mm). The mean for group 3 (16 patients with OSAHS only) was 4.29 mm (range 0-9 mm). The mean for group 4 (32 patients with LPR and OSAHS) was 4.00 mm (range 0-19.2 mm). The mean for group 1 was lower than the other 3 groups (P < 0.001). CONCLUSION: CT images including the tongue base allow precise measurement of LTT thickness. LTT > 2.7 mm was not identified in patients without OSAHS or LPR. The mean LTT for patients with LPR and/or OSAHS was significantly greater than for patients without either disease. PMID- 20304272 TI - Reliability of airway obstruction analyses from Sleep MRI sequences. AB - OBJECTIVE: A real-time MRI "movie" during natural sleep ("Sleep MRI") allows observation of dynamic airway obstructions in obstructive sleep apnea syndrome (OSAS) patients. The purpose of this article was to determine the reliability of assessing these obstructions. STUDY DESIGN: Cross-sectional diagnostic test evaluation. SETTING: Academic referral center. SUBJECTS AND METHODS: A total of 23 Sleep MRI sequences randomly selected from 20 consecutive OSAS patients were analyzed by two experienced sleep surgeons on two separate occasions separated by at least two weeks. Five dimensions were assessed: presence or absence of any obstruction, presence or absence of a retropalatal obstruction, presence or absence of a retroglossal obstruction, presence or absence of a swallow, and duration of an obstructive event. RESULTS: For all dimensions measured, intra rater reliability coefficients ranged from a low of 0.95 to a high of 1.0 for each rater. Inter-rater reliability coefficients ranged from a low of 0.85 to a high of 1.0. On two separate evaluations separated by at least two weeks, rater 1 identified a retropalatal obstruction in 100 percent of sequences, whereas rater 2 did so in 91 percent and 96 percent of the sequences, respectively. Retroglossal obstruction was identified in 57 percent (rater 1) and 65 percent (rater 2) of sequences. CONCLUSION: Intra-rater and inter-rater reliability coefficients are very high for determination of presence or absence of any obstruction, presence or absence of a retropalatal obstruction, presence or absence of a retroglossal obstruction, presence or absence of a swallow, and duration of obstruction from Sleep MRI sequences in OSAS patients. PMID- 20304273 TI - Screening for obstructive sleep apnea/hypopnea syndrome: subjective and objective factors. AB - OBJECTIVES: To determine the sensitivity and specificity of the Berlin Questionnaire and the Obstructive Sleep Apnea/Hypopnea Syndrome (OSAHS) score for individually predicting a diagnosis of OSAHS, and to propose a method for OSAHS screening incorporating objective and subjective factors. STUDY DESIGN: Cross sectional survey. SETTING: Tertiary care center. METHODS: Charts were reviewed from 223 consecutive patients for whom complete data regarding the Berlin questionnaire, OSAHS score (Friedman tongue position + tonsil size + body mass index grade), Epworth Sleepiness Scale, and visual analog scale for snoring were obtained prior to polysomnography (PSG). Sensitivity and specificity were determined for the Berlin questionnaire and OSAHS score for predicting an apnea hypopnea index (AHI) >or= 5. Patient data were subjected to multivariate stepwise discriminant analysis and used to construct a screening system based on the Fisher's linear classification equation. Results were cross-validated by PSG findings. RESULTS: In predicting an AHI >or= 5, the sensitivity and specificity, respectively, were 0.615 and 0.226 for the Berlin questionnaire, 0.863 and 0.468 for OSAHS score, and 0.82 and 0.834 for our predictive equation. When applied case-wise to the study population, this equation correctly predicted 82.5 percent of diagnoses. Accuracy was highest for severe OSAHS (87.4%) and lowest for mild disease (77.0%). Sensitivity was lowest for mild OSAHS (0.50). CONCLUSIONS: Neither the Berlin questionnaire nor the OSAHS score alone was both highly sensitive and specific for diagnosing OSAHS. By incorporating subjective and objective metrics into a single predictive equation, sensitivity and specificity were maximized, and 82.5 percent of diagnoses were accurately predicted. PMID- 20304274 TI - Gore-Tex medialization laryngoplasty for treatment of dysphagia. AB - OBJECTIVE: Gore-Tex medialization laryngoplasty is a well described procedure for the management of glottal incompetence with associated phonatory disturbance. Limited literature exists describing the use of this procedure in the management of dysphagia. We describe our experience with Gore-Tex medialization laryngoplasty and the treatment of dysphagia. STUDY DESIGN: Case series with chart review. SETTING: Tertiary referral center. SUBJECTS AND METHODS: Between April 2000 and September 2008, 189 Gore-Tex medialization laryngoplasties were performed on 180 patients by the senior author. Complete records and analysis were available for and performed on 121 procedures for 113 patients. The main outcome measures were discontinuation of gastrostomy tube (g-tube) use or avoidance of g-tube, as well as clinical subjective improvement in swallowing function. RESULTS: Fifty-seven of 113 (50%) patients had complaints of dysphagia at presentation, with 47 of 57 (82%) having an objective swallowing evaluation. Thirty-two of 47 (68%) had documented penetration and/or aspiration. Twenty of 57 (35%) patients with dysphagia required g-tubes for alimentation. Eleven of 20 (55%) patients were able to discontinue g-tube use after Gore-Tex medialization laryngoplasty, and an additional five patients with aspiration were able to avoid need for g-tubes with Gore-Tex medialization laryngoplasty and swallowing therapy. CONCLUSIONS: Gore-Tex medialization laryngoplasty is a well tolerated and well described treatment for the management of glottal incompetence. The procedure is an appropriate adjunct in dysphagia management for the appropriate patient population. PMID- 20304275 TI - Effects of type II thyroplasty on adductor spasmodic dysphonia. AB - OBJECTIVES: Type II thyroplasty, or laryngeal framework surgery, is based on the hypothesis that the effect of adductor spasmodic dysphonia (AdSD) on the voice is due to excessively tight closure of the glottis, hampering phonation. Most of the previous, partially effective treatments have aimed to relieve this tight closure, including recurrent laryngeal nerve section or avulsion, extirpation of the adductor muscle, and botulinum toxin injection, which is currently the most popular. The aim of this study was to assess the effects of type II thyroplasty on aerodynamic and acoustic findings in patients with AdSD. STUDY DESIGN: Case series. SETTING: University hospital. SUBJECTS AND METHODS: Ten patients with AdSD underwent type II thyroplasty between August 2006 and December 2008. Aerodynamic and acoustic analyses were performed prior to and six months after surgery. Mean flow rates (MFRs) and voice efficiency were evaluated with a phonation analyzer. Jitter, shimmer, the harmonics-to-noise ratio (HNR), standard deviation of the fundamental frequency (SDF0), and degree of voice breaks (DVB) were measured from each subject's longest sustained phonation sample of the vowel /a/. RESULTS: Voice efficiency improved significantly after surgery. No significant difference was found in the MFRs between before and after surgery. Jitter, shimmer, HNR, SDF0, and DVB improved significantly after surgery. CONCLUSIONS: Treatment of AdSD with type II thyroplasty significantly improved aerodynamic and acoustic findings. The results of this study suggest that type II thyroplasty provides relief from voice strangulation in patients with AdSD. PMID- 20304276 TI - Auto-crosslinked hyaluronan gel injections in phonosurgery. AB - OBJECTIVES: To evaluate the clinical performance of an auto-crosslinked gel obtained from hyaluronic acid (ACP-based gel) as an anti-adhesive agent and/or augmentative agent in vocal cord surgery for the treatment of vocal fold (VF) atrophy, sulcus vocalis, and postsurgery scarring as well as its tolerability at short- and long-term follow-up. STUDY DESIGN: This was a prospective multicenter trial conducted between 2007 and 2009. SETTING: Academic center. SUBJECTS AND METHODS: Inclusion criteria were patients with glottic gap due to previous endoscopic phonosurgery, VF scars, vocal cord atrophy, and sulcus vocalis. Forty patients who underwent endoscopic injection of hyaluronic acid under general anesthesia were enrolled. Two different injections sites were used: the thyroarytenoid muscle in cases of glottic gap for augmentative purposes, and the lamina propria for treatment of scars and sulcus vocalis. A voice-evaluation protocol was performed before surgery, at the first follow-up visit (3 mo), and at the final follow-up (12 mo). RESULTS: Follow-up data at three months were available for 38 patients, while data at 12 months follow-up were available for 27 patients. No side effects, hematoma, or infection and allergic reactions were reported in either the perioperative or postoperative period. Patients had statistically significant improvement in voice parameters compared with the baseline data at the first follow-up visit and at the 12-month follow-up. CONCLUSION: ACP-based gel seems to be a new tool in the challenging treatment of VF scarring, functioning as both an anti-adhesive product and an augmentation agent. Improvements in all glottal parameters and in both objective and subjective evaluation of voice performance were observed. PMID- 20304277 TI - The Baha system in patients with single-sided deafness and contralateral hearing loss. AB - OBJECTIVE: To evaluate the effectiveness of the Baha system in cases of single sided deafness (SSD) and mild to moderate hearing loss in the better-hearing ear. STUDY DESIGN: Prospective trial. SETTING: Tertiary otologic referral center. SUBJECTS AND METHODS: Twenty-one patients with SSD and mild to moderate hearing loss in the contralateral ear implanted with the Baha system between June 2006 and March 2008 were evaluated following Baha implantation and fitting with the Divino and Intenso processors. Pure-tone air and bone conduction thresholds, sound-field testing (aided and unaided in quiet and noise) of consonant nucleus consonant words (Northwestern University Auditory Test No. 6 words), and Hearing in Noise Test sentences were obtained. Patient satisfaction questionnaires were administered pre- and post-intervention for either device. RESULTS: Patients with SSD and mild to moderate hearing loss in the contralateral ear showed a statistically significant improvement in all measures with the use of the Divino or Intenso processors compared with the unaided situation. Change in hearing, as measured in noise testing word recognition scores, revealed a statistically significant difference between the two aided conditions favoring the Intenso (P < 0.05). The Glasgow Benefit Inventory revealed that 91 percent of the patients reported improvement in their quality of life and would recommend the procedure to others. CONCLUSION: The Baha system is effective in the rehabilitation of patients with SSD and mild to moderate hearing loss in the only hearing ear. Results of the current study suggest that either the Divino or Intenso processor was successful in reestablishing hearing from the deafened side. PMID- 20304278 TI - TriVerse versus molecular resonance-harvested grafts in single-stage Baha surgery. AB - OBJECTIVES: To assess complications occurring in patients with a bone-anchored cochlear stimulator (Baha) following split-thickness skin graft harvested with two surgical modalities: the TriVerse (TV) system and the molecular resonance generator (MR). STUDY DESIGN: Prospective, randomized, two-group (TV and MR) study of 24 patients who underwent Baha surgery. SETTING: Tertiary care institution. SUBJECTS AND METHODS: All patients (5 children, age range 6-14 yrs, median 8.3 yrs, and 16 adults, age range 30-73 yrs, median 60 yrs) underwent the one-stage procedure. The skin flap was harvested by use of the TV in 12 cases (2 children, 10 adults) and the MR generator in 12 (3 children, 9 adults). The main outcome measures were wound healing time, number of follow-up visits, degree of soft tissue reactions around the abutment, and need for revision surgery were examined. RESULTS: There was a clear difference between the TV- and MR-harvested skin graft groups in relation to severity of skin reactions and complete healing time. The TV group required from three to seven (median 4) visits as outpatients during the initial observation period until healing was complete. The MR group required only one to three (median 2) visits. Complete healing time was significantly lower in the MR group (range 7-12 days, median 10 days) compared to the TV group (range 15-28 days, median 16 days). In the TV group, two patients required in-office revision of the skin graft because of partial necrosis. CONCLUSIONS: In our experience, the MR-harvested split-thickness skin graft is superior to the TV technique. PMID- 20304279 TI - Long-term prognosis of low-frequency hearing loss and predictive factors for the 10-year outcome. AB - OBJECTIVES: To determine the long-term prognosis of low-frequency hearing loss and predictive factors for the 10-year outcome of low-frequency hearing loss. STUDY DESIGN: Case series with chart review. SETTING: Tertiary referral center. SUBJECTS AND METHODS: From 1979 to 1998, 466 consecutive patients with low frequency hearing loss received initial treatment at the Hearing and Tinnitus Clinic of Keio University Hospital. Of the 49 eligible patients, pure-tone threshold data obtained over a period of 10 years after onset of low-frequency hearing loss were available for analysis. To determine the progression of hearing loss, we analyzed audiometric pattern changes. We also examined how the following factors affected 10-year prognosis: sex, age, side of hearing loss, accompanying dizziness, pre-therapeutic hearing thresholds at low frequencies, initial therapy results, and fluctuation of hearing during the first year after onset. RESULTS: High- and pan-frequency hearing loss increased as time progressed. About half of the cases developed high- or pan-frequency hearing loss within 10 years of onset. Audiometric patterns measured at 10 years significantly correlated with those measured at one (r = 0.57), three (r = 0.73), and five years (r = 0.85). The 10 year prognosis significantly correlated with only two factors: initial therapy results (r = 0.49) and fluctuation of hearing during the first year (r = 0.43). CONCLUSIONS: About half of the cases in our study developed high- or pan frequency hearing loss within 10 years of onset of low-frequency hearing loss. The initial therapy results and fluctuation of hearing during the first year may indicate the long-term prognosis of patients presenting with low-frequency hearing loss. PMID- 20304280 TI - Intratympanic gentamicin treatment of patients with Meniere's disease with normal hearing. AB - OBJECTIVE: Understand the safety and outcomes of intratympanic gentamicin treatment in patients with Meniere's disease with normal hearing. STUDY DESIGN: Case series with chart review. SETTING: Tertiary referral center. SUBJECTS AND METHODS: A total of 224 patients with disabling Meniere's disease treated between May 1996 and June 2007 were grouped according to the American Academy of Otolaryngology-Head and Neck Surgery (AAO-HNS) 1995 Committee on Hearing and Equilibrium staging guidelines: stage 1 (<25 dB pure-tone average [PTA]); stage 2 through 4 (>25 dB PTA). Patients underwent self-treatment with intratympanic gentamicin (10 mg/mL) three times daily for one to eight weeks. Outcome measures included pre- and post-treatment speech discrimination score (SDS), PTA, electronystagmography, vertigo relief, and statistical analysis utilizing the Pearson chi(2) test. RESULTS: Twenty-two (88%) of 24 patients with stage 1 Meniere's disease showed unchanged or improved SDS. All 24 patients showed a mean PTA loss of 8 dB. Seventeen (71%) patients reported complete or improved vertigo control. One hundred sixteen (59%) of 200 patients with stage 2 through 4 Meniere's disease showed unchanged or improved SDS. All 200 patients showed a mean PTA loss of 11 dB. One hundred forty-eight (74%) patients reported complete or improved vertigo control. CONCLUSIONS: Patients with stage 1 Meniere's disease appear to have similar vertigo control with better hearing preservation than patients with advanced disease when treated with low-dose intratympanic gentamicin (10 mg/mL). PMID- 20304281 TI - A novel surgical technique for management of tinnitus due to high dehiscent jugular bulb. AB - OBJECTIVES: To assess the effectiveness of middle ear floor reconstruction in management of vascular tinnitus due to high jugular bulb with dehiscent middle ear floor. STUDY DESIGN: Case series with chart review. SETTING: Tertiary academic medical center. SUBJECTS AND METHODS: We reviewed the medical records of seven patients with high dehiscent jugular bulb, presenting with incapacitating pulsatile roaring tinnitus that was abolished by digital compression of the ipsilateral jugular vein, from January 2002 to December 2006. The diagnosis was confirmed by CT scan of the temporal bone (bone window, coronal views). The seven patients were surgically explored, five under local anesthesia (to monitor the results with possible intraoperative revision) and two under general endotracheal anesthesia, for middle ear floor reconstruction that was done using bone dust, perichondrium, and tragal cartilage (mean follow-up 28 months). RESULTS: Of the seven patients, tinnitus disappeared in four (57%) and decreased in one. The overall improvement was five of seven (71%). One patient had postoperative increased intracranial pressure. CONCLUSION: The preliminary results suggest that surgical reconstruction of the middle ear floor under local anesthesia offers valuable treatment for patients with incapacitating tinnitus due to dehiscent middle ear floor. However, the risk of sigmoid sinus thrombosis should be considered. To our knowledge, this is the first trial of multilayer reconstruction of the middle ear floor dehiscence to manage high jugular bulb causing tinnitus. PMID- 20304282 TI - Postoperative management following sphincter pharyngoplasty. AB - OBJECTIVE: To evaluate postoperative airway-associated outcomes following sphincter pharyngoplasty. STUDY DESIGN: Case series with chart review. SETTING: Academic tertiary care medical center. SUBJECTS AND METHODS: Postoperative management of sphincter pharyngoplasty (SP) conventionally includes overnight observation to monitor for upper airway obstruction. To evaluate for postoperative airway-related outcomes, 36 patients who underwent SP between April 2003 and January 2009 were evaluated retrospectively. RESULTS: Mean patient age was 8.1 (SD 4.3) years. Mean follow-up was 6.5 (SD 10.7) months. Cleft palate (36.1%), velo-cardio-facial syndrome (22.2%), and post-adenoidectomy (16.7%) were the most common causes of velopharyngeal insufficiency. All patients underwent overnight observation postoperatively. Mean hospital stay was 1.2 (SD 0.5) days. Five patients remained inpatient two or three days owing to fever (2 patients), bleeding ear after concurrent otoplasty (1 patient), minimal oropharyngeal bleeding with spontaneous resolution (1 patient), and medication allergy (1 patient). No patient had a documented apneic event or desaturation below 95 percent. Although no desaturations were documented, four patients received supplemental oxygen: three for less than two hours, and one for 12 hours. All patients had adequate oral intake and pain control on oral medications prior to discharge; nine patients required one to three doses of intravenous narcotic medication for pain on postoperative day zero. CONCLUSION: Upper airway obstruction requiring overnight observation following SP is uncommon. In otherwise healthy patients, performing SP in an outpatient setting, given appropriate recovery room evaluation for airway concerns, oral intake, and pain control, should be considered. PMID- 20304283 TI - Disease relapse after segmental resection and free flap reconstruction for mandibular osteoradionecrosis. AB - OBJECTIVE: The objective of this study was to assess the outcomes, complications, and incidence of disease recurrence of mandibular osteoradionecrosis (ORN) after resection and microvascular free flap reconstruction. STUDY DESIGN: Case series with chart review. SETTING: Academic medical center. SUBJECTS AND METHODS: Retrospective patient data review of 40 patients with mandibular ORN who were treated by segmental mandibulectomy and microvascular reconstruction between 1995 and 2009. All patients received radiation therapy for previous head and neck cancer, and 12 of 40 patients received concurrent chemotherapy. All patients failed to respond to conservative management. There were 26 males and 14 females, with a median age of 62 years. Median follow-up was 17.4 months. RESULTS: There were no free flap failures. The incidence of wound-related complications was 55 percent. Median time to complication was 10.6 months. Ten (25%) patients developed symptoms of residual or recurrent ORN, with 70 percent of the recurrences arising in unresected condyles that were adjacent to the segmental mandibulectomy. Statistical analysis revealed that current smokers were at reduced risk to develop residual or recurrent ORN. CONCLUSION: This present study confirms that microvascular free flaps are reliable for treatment of advanced mandibular ORN. Nevertheless, there remains a 55 percent incidence of wound healing complications. The lack of objective clinical criteria to judge the appropriate amount of mandible resection in patients with ORN remains an unresolved issue that resulted in the development of recurrent ORN in 25 percent of patients. Further investigations are needed to better understand the pathophysiology of ORN to prevent postoperative wound complications and disease recurrence. PMID- 20304284 TI - Neck restaging with sentinel node biopsy in T1-T2N0 oral and oropharyngeal cancer: Why and how? AB - OBJECTIVE: To evaluate the lack of accuracy in neck staging with the classical technique (i.e., neck dissection and routine histopathology) with the sentinel node (SN) biopsy in oral and oropharyngeal T1-T2N0 cancer. STUDY DESIGN: Cross sectional study with planned data collection. SETTING: Tertiary center care. SUBJECTS AND METHODS: In 50 consecutive patients, the pathological stage of sentinel node (pSN) was established after analyzing SN biopsies (n = 148) using serial sectioning and immunohistochemistry. Systematic selective neck dissection was performed. The pN stage was established with routine histopathologic analysis of both the non-SN (n = 1075) and the 148 SN biopsies. RESULTS: The sensitivity and negative predictive value of pSN staging were 100 percent. Conversely, if one considers pSN staging procedure as the reference test for micro- and macro metastasis diagnosis, the sensitivity of the classical pN staging procedure was 50 percent (9/1; 95% CI 26.9-73.1) and its negative predictive value was 78 percent (95% CI 61.9-88.8). Fifteen patients (30%) were upstaged, including nine cases from pN0 to pSN >or= 1 and six cases from pN1 to pSN2. Two of the pN0-pSN1 upstaged patients died with relapsed neck disease. CONCLUSION: The SN biopsy technique appeared to be the best staging method in cN0 patients and provided evidence that routinely undiagnosed lymph node invasion may have clinical significance. PMID- 20304285 TI - High-speed digital imaging of the neoglottis after supracricoid laryngectomy with cricohyoidoepiglottopexy. AB - OBJECTIVE: To determine the utility of high-speed digital imaging (HSDI) in evaluating vocal kinetics of the neoglottis after supracricoid laryngectomy with cricohyoidoepiglottopexy (SCL-CHEP). STUDY DESIGN: Case series. SETTING: The University of Tokyo Hospital. SUBJECTS AND METHODS: High-speed digital recordings of laryngeal images were obtained from six patients after SCL-CHEP to clarify the vocal kinetics of the postoperative neoglottis. Simultaneous recording of electroglottograms (EGGs) were obtained and multiline kymograms were generated on the basis of the recorded images. The distribution of frequency, amplitude, and phase in the neoglottis were visualized by using gradients of colors superimposed onto the glottal and supraglottal areas of laryngeal images to produce laryngeal topograms. Furthermore, waveforms of estimated laryngeal sound source (ELSS) were obtained on the basis of glottal inverse filtering of the vocal signal to reflect vibratory motions in the neoglottis. The vibratory part of the neoglottis was determined as a possible sound source when the frequencies of the ELSS, EGG, and laryngeal topograms, as well as the waveforms of ELSS, EGG, and kymograms, were consistent with each other. RESULTS: Spaces between the arytenoid(s) and epiglottis (5 patients) or pyriform sinus mucosa (1 patient) were estimated as the major source of sound during postoperative vocalization. The possible sound source could be determined by HSDI, even in the neoglottis, with more than one vibratory position. CONCLUSION: HSDI could be useful for evaluating the vocal kinetics of the neoglottis after SCL-CHEP. PMID- 20304286 TI - Bax, cytochrome c, and caspase-8 staining in parotid cancer patients: markers of susceptibility in radiotherapy? AB - OBJECTIVE: Negative bcl-2 and HLA-DR protein expression have been associated with responsiveness to adjuvant radiotherapy in surgically treated parotid cancer patients. The aim of this study was to investigate the prognostic significance of bax, cytochrome c, and caspase-8 protein expression in a group of surgically treated patients to determine whether they also suggest markers of responsiveness to adjuvant radiotherapy. STUDY DESIGN: Historical cohort study. SETTING: Otolaryngology department in a university hospital. SUBJECTS AND METHODS: The immunohistochemical expression of bax, cytochrome c, and caspase-8 were studied in paraffin-embedded tissue specimens originating from 27 surgically treated parotid cancer patients and nine patients with Warthin parotid tumors (control group) and correlated with the patients' clinicopathological characteristics and clinical outcome. RESULTS: Caspase-8 negative staining was more frequently observed in higher TNM stages and in tumors measuring more than 4 cm (P = 0.009 and P = 0.018, respectively). Caspase-8 (-)/cytochrome c (-) patients carried low grade lesions without nodal involvement (P = 0.01 and P = 0.05, respectively). Caspase-8 (-) patients who received postoperative radiotherapy presented a significantly increased disease-free survival compared to those who did not (P = 0.04). Patients bearing bax (-) tumors who received postoperative radiotherapy presented an improved four-year disease-free survival compared to bax (-) patients who did not receive any type of adjuvant radiotherapy (P = 0.017). CONCLUSION: Bax, cytochrome c, and caspase-8 protein expression failed to independently predict survival in parotid cancer patients. However, patients with bax (-) or caspase-8 (-) tumors should be considered as candidates for adjuvant radiotherapy in order to achieve better local disease control. PMID- 20304287 TI - H1N1 influenza A presenting as bacterial tracheitis. AB - Six cases of bacterial tracheitis (BT) occurring early in the 2009 flu season have been isolated in conjunction with the H1N1 strain of influenza A (H1N1). No previous H1N1 cases have presented as BT in the literature to date. We would like to discuss viral coinfection in BT patients and how this new strain may affect the rate and type of presentation encountered. The life-threatening potential of BT and the pandemic proportion of H1N1 highlight a possibly dangerous combination that should be recognized by the otolaryngology community. In hospitalized patients with presumed BT, consideration should be given to routine H1N1 testing and the addition of antiviral medication when indicated as this entity is further investigated. PMID- 20304288 TI - Acoustic recordings in human ear canals to sounds at different locations. AB - The head and pinna shape the sound reaching the tympanum. We explored this signal transformation in humans and a mini basketball for different sound locations in an anechoic chamber. For humans, we embedded microphones in ear molds that were custom fitted to the subject's ear canal. For the ball, the microphones were flush with the surface at +/- 90 degrees azimuths on the equator. Sounds were generated with a custom point source. In the ball, the signal level was nearly flat across frequency, with no gains. In contrast, in the ears, signal level changed in a complex way across frequency, with considerable gains. For frequencies < 2 kHz, the interaural level difference (ILD) increased with decreasing distance similarly in the human ears and ball. For frequencies > 4 kHz, ILDs in the human ears were larger and more complex than those in the ball such that the human ILDs were nonmonotonic with distance whereas the ball ILDs were monotonic with distance. PMID- 20304289 TI - Awake extracorporeal membrane oxygenation for management of critical distal tracheal obstruction. PMID- 20304290 TI - Seal it and reveal it: postoperative otoplasty care using a silicone-based occlusive dressing. PMID- 20304291 TI - Mucoepidermoid carcinoma of the external auditory canal. PMID- 20304292 TI - Retained tracheotomy suture: nine years of morbidity. PMID- 20304293 TI - Life-threatening tension subcutaneous emphysema as a complication of open tracheostomy. PMID- 20304294 TI - Isolating Candida epiglottitis. PMID- 20304295 TI - Guillain-Barre syndrome presenting as epiglottitis in a child. PMID- 20304296 TI - The relationship between the air-bone gap and the size of superior semicircular canal dehiscence. PMID- 20304298 TI - [Management of Gaucher disease in France]. PMID- 20304299 TI - [Central nervous system involvement in Gaucher disease]. PMID- 20304300 TI - [Gaucher disease and pregnancy]. PMID- 20304301 TI - [Gaucher disease in children]. PMID- 20304302 TI - [Biomarkers in Gaucher disease: up-to-date]. PMID- 20304303 TI - [Skeletal manifestations in Gaucher disease: imaging findings and follow up]. PMID- 20304304 TI - [Osteoarticular manifestations of Gaucher's Disease and imiglucerase efficacy on bone mineral density in adults. Review of literature]. PMID- 20304305 TI - [Management of bone loss in patients with Gaucher disease]. PMID- 20304306 TI - [Home therapy in Gaucher disease]. PMID- 20304307 TI - [Gaucher disease diagnosed in pediatrics: an early bone involvement]. PMID- 20304308 TI - [Persistent anemia in a patient with Gaucher disease and heterozygous drepanocytosis]. PMID- 20304309 TI - [Major hyperferritinemia, autoimmune thrombocytopenic purpura and lymphocytic lymphoma in Gaucher disease]. PMID- 20304310 TI - [Type 1 Gaucher disease and pregnancy]. PMID- 20304311 TI - [Hematological aspects of Gaucher disease]. PMID- 20304312 TI - [Diagnosis of type 1 Gaucher disease: follow-up in internal medicine, disease course aspects in 17 years]. PMID- 20304313 TI - [Benefits of early enzyme replacement therapy in two children with type 1 Gaucher disease]. PMID- 20304314 TI - [Treatment of bone involvement in Gaucher diseases with imiglucerase combined with miglustat]. PMID- 20304315 TI - Ultrasound, computed tomography, and magnetic resonance: the "central nervous system" of every radiology practice. PMID- 20304316 TI - Improving patient safety in radiology: concepts for a comprehensive patient safety program. AB - A comprehensive safety program can have a positive influence on safety performance and safety culture within a department of radiology. The program should include both vertical interventions aimed at specific areas of potential safety errors as well as horizontal interventions aimed at improving safety culture and decreasing the baseline rate of human error. In our opinion, the key cultural transformations that must occur to improve safety culture include recognition that safety is an issue, emphasis that everyone is accountable for patient safety, and creating a culture where people are expected and encouraged to speak up in the face of uncertainty. The article describes the horizontal interventions to improve patient safety used in our department. PMID- 20304317 TI - Infant craniospinal ultrasonography: beyond hemorrhage and hydrocephalus. AB - Ultrasonography is widely used for screening for neonatal intracranial hemorrhage, hydrocephalus, and cord tethering in young infants. Proper interpretation of infant cranial and spinal ultrasound examinations requires not only familiarity with the appearances of these disorders, but also recognition of imaging artifacts capable of mimicking pathology and awareness of developmental variants and conditions that occupy a borderline position along the spectrum from normal to abnormal. This article will review the current understanding of the ultrasonographic characteristics and clinical relevance of these imaging artifacts, developmental variants, and quasi-pathologic conditions to avoid diagnostic pitfalls and guide appropriate patient management. PMID- 20304318 TI - State-of-the-art in pediatric body and musculoskeletal magnetic resonance imaging. AB - Pediatric body and musculoskeletal MRI has seen tremendous advances over the past few years. These advances have enabled high-quality imaging in even the smallest children and expanded the range of clinical problems amenable to MRI. In this review, we highlight some advances: transition to 3 Tesla, parallel imaging, motion compensation, and new contrast agents. Given the increasing saliency of concerns regarding ionizing radiation from computed tomography, these advances could not be more welcome. PMID- 20304319 TI - Imaging approach to acute hematogenous osteomyelitis in children: an update. AB - Acute hematogenous osteomyelitis (AHOM) is primarily a disease in infants and children. Early diagnosis of AHOM in children is essential to prevent complications and long-term morbidity. The diagnosis of AHOM could be challenging as presentation varies with the child's age and type of pathogen. It is the role of the radiologist to suggest the appropriate imaging modality for the diagnosis of AHOM and evaluation of complications. This article discusses the current multimodality imaging approach for early diagnosis of AHOM, and evaluation of complications to guide treatment. PMID- 20304320 TI - Magnetic resonance sleep studies in the evaluation of children with obstructive sleep apnea. AB - Magnetic resonance (MR) sleep studies have been shown to be a useful tool in the evaluation and surgical planning of children with persistent obstructive sleep apnea. MR sleep studies include sequences to evaluate both static anatomic and well as dynamic motion information about the airway. The combination of the information about anatomic abnormalties and patterns of collapse can help in surgical decision making. The most common identified entities include recurrent enlargement of the adenoid tonsils, enlargement of the lingual tonsils, abnormal soft palate, glossoptosis, and hypopharyngeal collapse. This review discusses multiple aspects of MR sleep studies including indications, patient preparation, MR protocols, and commonly made diagnoses. PMID- 20304322 TI - Current imaging of prenatally diagnosed congenital lung lesions. AB - Congenital lung lesions refer to a spectrum of pulmonary developmental anomalies including, but not limited to, bronchial atresia, congenital pulmonary airway malformation (formerly known as congenital cystic adenomatoid malformation) and bronchopulmonary sequestration. These anomalies comprise about 90% of the anomalies seen in clinical practice. The advent of prenatal sonography and, more recently, fetal magnetic resonance imaging has changed our understanding and practice in the evaluation of congenital lung lesions. Postnatal imaging using low-dose computed tomography angiography (CTA) is extremely useful as it may provide information essential for differential diagnosis by allowing multiplanar reconstructions of the airway, lung parenchyma, and vasculature. The use of iodine in CTA permits the application of low-dose radiation protocols in these young patients. The purpose of this article is to emphasize the technical factors that may optimize low-dose CTA evaluation of these lesions. We also provide a description of prenatal imaging findings and helpful diagnostic clues that may be useful for the characterization of the most commonly encountered prenatally diagnosed pulmonary developmental anomalies. PMID- 20304321 TI - Contemporary pediatric gynecologic imaging. AB - Ultrasound is the primary screening modality for the evaluation of pediatric gynecologic maladies. Magnetic resonance imaging (MRI) is used progressively more in this field, particularly for the evaluation of complex pelvic masses and congenital anomalies. However, ultrasound remains the preferred modality due to the excellent visualization, the dynamic nature of the examination modality, lack of ionizing radiation and sedation risks, and comparatively lower cost. MRI is generally a second-line examination and is preferred over computed tomography as it does not involve the use of ionizing radiation. Additionally, visualization of the female reproductive system anatomy with MRI is superior to computed tomography, the latter being reserved generally for tumor staging. Fluoroscopic examinations and abdominal radiographs can provide additional information that may support a diagnosis. PMID- 20304323 TI - Left pulmonary artery sling--anatomy and imaging. AB - Distinctive imaging findings are present when the left pulmonary artery (LPA) arises from the right pulmonary artery and forms a sling around the airway passing between airway and esophagus to reach the left lung. It is important to recognize the 2 distinct types of pulmonary sling. The less complex type I is associated with tracheobronchomalacia and is often managed successfully by LPA reimplantation. The more common and more complex type II is strongly associated with long segment tracheal stenosis. Appropriate management needs to address the airway abnormality in addition to the aberrant LPA. Both types, especially type II, are associated with cardiovascular, pulmonary, and other abnormalities that also need to be considered in therapeutic decisions. The role of imaging is to identify, define, and display the relevant anatomic relationships to facilitate appropriate management. Recent surgical advances have increased the likelihood of success of surgical correction of long segment airway stenosis. PMID- 20304324 TI - Pediatric advanced imaging and informatics: state of the art. AB - Pediatric imaging has been at the forefront of radiology innovation since the days of Roentgen. In the past 2 decades, evolving computer technology and sophisticated software algorithms have rapidly advanced how pediatric radiologic examinations are acquired and displayed, interpreted and communicated, and stored and retrieved. Cost-effective use of this state of the art technology requires fundamental knowledge of the modalities, workstations, and informatics that guide advanced pediatric imaging in the current digital era. Equally important is an understanding of the advanced clinical applications and evidence supporting this use. In the first part of this review article, after a brief introduction and historical overview, technical principles are discussed. This is followed by a review of advanced clinical applications for fetal, cardiovascular, central nervous system, neck, thoracic, gastrointestinal, genitourinary, musculoskeletal, and virtual-autopsy imaging. PMID- 20304325 TI - Axonal damage in leukodystrophies. AB - Recent advances in radioimaging and immunocytological techniques have enhanced investigations of neurometabolites and axons, giving rise to renewed interest in human white-matter disorders. A strong correlation between axonal loss and disability in some demyelination diseases (e.g., multiple sclerosis) led to several studies examining the mechanisms of axonal damage. We review the relationship between demyelination, axon loss, and neurologic progression, and the role of advanced neuroimaging in children with different types of leukodystrophies, i.e., X-linked adrenoleukodystrophy, metachromatic leukodysrtophy, Krabbe's disease, Pelizaeus-Merzbacher disease, and Alexander's disease. PMID- 20304326 TI - The prevalence of neuropsychiatric disorders in Sydenham's chorea. AB - Sydenham's chorea is a rare movement disorder associated with streptococcal infection. The co-occurrence of neuropsychiatric symptoms has raised the question of whether streptococcal infection could trigger these symptoms without chorea. This study evaluated the prevalence of behavioral diagnoses before, during, and after the onset of chorea in a cohort of children with a history of Sydenham's chorea for whom demographic and clinical data were available. In all, 28 Sydenham's chorea patients were evaluated, with a mean age of 10.3 years. Retrospective analysis was performed for subject demographics, streptococcal titers, and presence of arthritis and carditis. Structured diagnostic interviews were performed on 14 available patients and parents. Streptococcal titers and duration of treatment for chorea were compared between groups. The prevalence of attention deficit hyperactivity disorder before and after chorea was 30 and 37%, respectively. The proportion of children meeting combined, subthreshold, and suprathreshold criteria before, during, and after Sydenham's chorea was 71, 79, and 79% for anxiety and 19, 69, and 44% for depression. Streptococcal antibody titers and duration of treatment did not correlate with attention deficit hyperactivity disorder, depression, or anxiety disorders. During and after the diagnosis of Sydenham's chorea, clinicians should be vigilant for signs and symptoms of anxiety, depression, and attention deficit hyperactivity disorder. PMID- 20304327 TI - Melatonin and sleep-related problems in children with intractable epilepsy. AB - Children with epilepsy have high rates of sleep problems. Melatonin has been advocated in treatment of sleep disorders, and its beneficial effect has been confirmed in insomnia. The aim of this study was to assess melatonin levels in children with intractable epilepsy and its relation to pattern of sleep and characteristics of seizure disorder, as well as the effect of melatonin therapy on those parameters. The study was conducted on 23 children with intractable epilepsy and 14 children with controlled seizures. Patients were evaluated by psychometric sleep assessment and assay of diurnal and nocturnal melatonin levels. Children with intractable epilepsy received oral melatonin before bedtime. They were reassessed after 3 months. Children with intractable epilepsy had higher scores for each category of sleep walking, forcible teeth grinding, and sleep apnea. At the end of therapeutic trial, patients with intractable epilepsy exhibited significant improvement in bedtime resistance, sleep duration, sleep latency, frequent nocturnal arousals, sleep walking, excessive daytime sleepiness, nocturnal enuresis, forcible teeth grinding, sleep apnea, and Epworth sleepiness scores. There was also significant reduction in seizure severity. Thus, use of melatonin in patients with intractable seizures was associated with improvement of both many sleep-related phenomena and the severity of seizures. PMID- 20304328 TI - Neuropathology in succinic semialdehyde dehydrogenase deficiency. AB - Reported here is the novel finding of neuropathology in a patient with succinic semialdehyde dehydrogenase deficiency, an inherited disorder of gamma aminobutyric acid metabolism characterized by intellectual deficiency, hypotonia, and epilepsy, with 4-hydroxybutyric aciduria and abnormalities of the globus pallidus on neuroimaging. A 19-year-old woman of European origin with a neurodevelopmental disorder and epilepsy died unexpectedly in 1998. A postmortem examination was performed, with a final diagnosis of sudden unexpected death in epilepsy patients. Eight years later, her sister with a neurodevelopmental disorder presented at 13 years of age with seizures and was diagnosed with succinic semialdehyde dehydrogenase deficiency. In the decedent, succinic semialdehyde dehydrogenase deficiency was established at the molecular level, 10 years after her death, using genomic DNA from brain tissue specimens. The neuropathologic findings revealed striking discoloration of the globi pallidi, leptomeningeal congestion, and a scar in the frontal cortex. After detection of the pathogenic homozygous mutation c.1226G>A, p.Gly409Asp in the living sister, it was confirmed in the decedent. An underlying metabolic disease may be an additional risk factor for sudden unexpected death in epilepsy patients. PMID- 20304329 TI - Cerebellar mutism in pediatric acute disseminated encephalomyelitis. AB - Acute disseminated encephalomyelitis is a demyelinating process affecting multiple areas of the central nervous system, frequently including the cerebellum. Cerebellar insult may lead to absence of speech or cerebellar mutism. Cerebellar mutism often occurs in young children after posterior fossa tumor resection, and generally appears as part of a larger subset of neurobehavioral signs and personality changes known as posterior fossa syndrome. Information on the impact of widespread cerebellar involvement on speech production, behavior, and long-term outcomes in acute disseminated encephalomyelitis is limited. We describe cases of acute disseminated encephalomyelitis with predominantly cerebellar involvement, with specific attention to cerebellar mutism. We conducted a retrospective chart review of children diagnosed with acute disseminated encephalomyelitis between 2005-2009 at a pediatric multiple sclerosis and demyelinating disorders clinic. Of 19 patients diagnosed with acute disseminated encephalomyelitis, six (32%) manifested primary cerebellar involvement. Of these six, four (67%) exhibited acute language disturbance, with three (50%) exhibiting mutism. The three patients with cerebellar mutism experienced protracted speech and language deficits after follow-ups from 6 months to 4 years. Widespread cerebellar involvement in acute disseminated encephalomyelitis may result in cerebellar mutism, in addition to persistent neurocognitive and behavioral problems. PMID- 20304330 TI - Cryptococcosis in nonhuman immunodeficiency virus-infected children. AB - Between 1991-2006, nine patients below age 18 years, with a microbiologic documentation of Cryptococcus neoformans infection and no evidence of human immunodeficiency virus infection, were identified and treated at Chang Gung Children's Hospital. All exhibited central nervous system involvement. Seven patients were female (age range, 9-16 years; mean age, 13.7 years). Five patients (56%) manifested underlying diseases and were receiving either steroid or immunosuppressant treatment at time of disease onset. Eight patients presented with meningitis. Headache, vomiting, and focal neurologic signs were the most common presentations. Protein and sugar levels in cerebrospinal fluid were within normal range in seven cases, whereas India ink smear and cryptococcal antigen testing were positive in 87% (7/8) and 78% (7/9) of patients, respectively. With prompt antifungal therapy, all survived, but one presented the sequel of blindness. Cryptococcosis is uncommon in the nonhuman immunodeficiency virus infected pediatric population. Clinicians should take into account a diagnosis of central nervous system cryptococcosis when children present with prolonged headache, vomiting, and focal neurologic signs. Indian ink stain and cryptococcal antigen testing of cerebrospinal fluid should be performed. PMID- 20304331 TI - Caregiver's burden and quality of life in mitochondrial disease. AB - A child's health inevitably affects the parents' psychologic health and quality of life, especially for mothers of disabled children. Caregiver burden and health related quality of life were investigated in mothers of children with mitochondrial disease, compared with mothers of children with intractable epilepsy. Mothers of children with mitochondrial disease (n = 33) and intractable epilepsy (n = 32) were recruited. The Zarit Burden Inventory, the Medical Outcomes Short Form 36, short version of the World Health Organization Quality of Life, Beck Depression Inventory, and Beck Anxiety Inventory were administered to all participants. Except for duration of illness and number of previous hospitalizations, there was no significant difference in recorded variables between the two groups. Mothers of children with mitochondrial disease had significantly higher caregiver burden and poorer health-related quality of life, particularly related to role limitations, vitality, and mental health. They also had greater levels of depression and anxiety. After adjustment for all covariates, caregiver anxiety was the most important factor affecting overall caregiver burden. With mitochondrial disease, the possibility of maternal inheritance and scarcity of information about the disease might increase anxiety and thus eventually also the caregiver burden. Accurate information about rare diseases provided to caregivers could be helpful in reducing their anxiety. PMID- 20304332 TI - Seizure susceptibility due to antihistamines in febrile seizures. AB - The aim of this study was to determine whether seizure susceptibility due to antihistamines is provoked in patients with febrile seizures. The study population comprised 14 patients with simple febrile seizures and 35 patients with complex febrile seizures. Detailed clinical manifestations were compared between patients with and without administration of antihistamine. The time from fever detection to the seizure onset was significantly shorter in the antihistamine group than that in the nonantihistamine group, and the duration of seizures was significantly longer in the antihistamine group than that in nonantihistamine group. Interleukin-1beta is thought to be associated with causing febrile seizures via its dual role as a pyrogen and convulsant substance. Moreover, interleukin-1beta may activate the turnover of hypothalamic neural histamine. These considerations, along with the present results, suggest that the depletion of hypothalamic neuronal histamine induced by antihistamines may increase neuronal excitability, thereby increasing seizure susceptibility in patients with febrile seizures. PMID- 20304333 TI - Alien hand syndrome in Parry-Romberg syndrome. AB - A pediatric patient with diagnosis of Parry-Romberg syndrome, or progressive hemifacial atrophy, presented with new-onset unilateral alien hand syndrome, which was attributed to focal progressive atrophy and gliosis in the contralateral thalamus observed on serial neuroimaging. This case illustrates not only the clinical-radiographic correlation between alien hand syndrome and contralateral thalamic lesion, but also involvement of deep gray structure in Parry-Romberg syndrome causing a rare movement disorder. PMID- 20304334 TI - Severe cerebral vaso-occlusive disease in macrophage activation syndrome. AB - A 14-year-old girl was diagnosed with macrophage activation syndrome, based on clinical presentation, laboratory tests, and bone marrow aspirate findings. She developed severe central nervous system involvement in the form of seizure disorder and severe diffuse occlusive cerebral vasculopathy, with extensive collateral circulation consistent with moyamoya disease. To our knowledge, this description is the first of these findings in association with macrophage activation syndrome. PMID- 20304335 TI - Fanconi syndrome caused by valproic acid. AB - Two severely disabled children with epilepsy, a 6-year-old boy and a 15-year-old girl, had been treated with valproic acid from the ages of 5 and 6 months, respectively, and developed Fanconi syndrome. Both patients were bedridden and fed by means of a nasogastric or gastrostomy tube. Because their Fanconi syndrome appeared to be caused by valproic acid, that treatment was stopped; for both patients, the Fanconi syndrome then resolved, in 6 months and 3 months, respectively. Severely handicapped children may be at risk for valproic acid induced renal involvement. Although renal involvement is an uncommon adverse effect of valproic acid, Fanconi syndrome due to valproic acid therapy has rarely been reported. In the few previous cases, the patients, who were bedridden and fed through a nasogastric or a gastrostomy tube, had taken valproic acid for an average of approximately 7 years. Nonetheless, their valproic acid blood levels were normal. Urinary abnormalities disappeared in an average of 4 months, as also in the present two cases. The potential for Fanconi syndrome must be considered in children with epilepsy who are treated with valproic acid, especially in severely disabled children. PMID- 20304336 TI - Endovascular therapy in pediatric intracranial carotid artery dissection. AB - Intracranial carotid dissection is an underrecognized cause of childhood stroke, and, in the face of limited therapeutic experience, its management is controversial. Reported here is the case of a 12-year-old girl who experienced an intracranial carotid artery dissection with progressive and symptomatic occlusion of the middle cerebral artery. Endovascular treatment with intra-arterial thrombolysis and stent reconstruction was successfully performed to recanalize the occluded arterial segment. Current management of intracranial carotid dissection in children is reviewed, with discussion of the reasons for aggressive endovascular intervention. PMID- 20304337 TI - Brainstem dysgenesis in an infant prenatally exposed to cocaine. AB - Many authors described the effects on the fetus of maternal cocaine abuse during pregnancy. Vasoconstriction appears to be the common mechanism of action leading to a wide range of fetal anomalies. We report on an infant with multiple cranial nerve involvement attributable to brainstem dysgenesis, born to a cocaine addicted mother. PMID- 20304338 TI - Convalescence disguising disease progression in neonatal herpes encephalitis. AB - Herpes encephalitis in neonates or young infants entails significant risk of mortality or morbidity. Prompt and aggressive treatment may lessen the chronic toll of herpes encephalitis. Unfortunately, an apparent uneventful recovery from herpes encephalitis may disguise evolving cerebral devastation. The discordance between evolving cerebral injury revealed by imaging and a patient's clinical improvement is illustrated by two patients, treated a decade apart. PMID- 20304339 TI - Acute motor and sensory axonal neuropathy in LEOPARD syndrome. AB - A case of acute predominantly axonal motor and sensory neuropathy (AMSAN) is reported in a 16-year-old boy with LEOPARD syndrome (the acronym represents lentigines, ECG conduction abnormalities, ocular hypertelorism, pulmonic stenosis, abnormal genitalia, retardation of growth, and sensorineural deafness). The presentation was atypical for acute motor and sensory axonal neuropathy, in that this patient had progression of symptoms of more than 4 weeks and there were signs of reinnervation in the acute phase. Treatment response to intravenous immunoglobulins was excellent. In patients with LEOPARD syndrome and acute neuropathies, treatment with intravenous immunoglobulins should be considered. PMID- 20304340 TI - Therapeutic hypothermia after cardiac arrest: another confounding factor in brain death testing. PMID- 20304342 TI - Are brain death findings reversible? PMID- 20304344 TI - [Hepatitis B remains a public health problem in France]. PMID- 20304345 TI - [Mobilize parents to vaccinate their children against hepatitis B: the role of the pediatrician]. PMID- 20304346 TI - Statin therapy: the new perioperative "magic bullet" for all surgical procedures? PMID- 20304347 TI - Perioperative chronic use of statins and the risk of muscle complaints in patients undergoing knee and hip endoprosthesis surgery. AB - STUDY OBJECTIVE: To assess whether regular statin therapy enhances muscular and hepatic deterioration and muscle complaints in patients undergoing elective arthroplasty. DESIGN: Prospective, case-controlled, observational study. SETTING: Tertiary-level university teaching hospital in Eastern Finland. PATIENTS: 48 ASA physical status I, II, and III patients, aged 51 to 84 years, 24 of whom were scheduled for hip arthroplasty (12 pts with and 12 without statin therapy) and 24 patients who were to undergo knee arthroplasty (12 pts with and 12 without statin therapy). INTERVENTIONS: Before and after surgery, all patients were interviewed for muscular and hepatic symptoms and signs. MAIN MEASUREMENTS: S-creatine kinase, S-alanine aminotransferase, P-creatinine, S-lactate dehydrogenase, P potassium, S-myoglobin, and U-myoglobin were measured at baseline and at 6, 24, and 72 hours after surgery. MAIN RESULTS: S-creatine kinase and S-myoglobin increased in all study groups at 6 hours after surgery and remained elevated for 72 hours, with no differences noted in patients treated with or without statins. There was no increase in the amount of muscular or hepatic complaints after surgery. CONCLUSION: Long-term statin therapy does not appear to increase the risk of muscular adverse effects in patients receiving major endoprosthesis surgery. PMID- 20304348 TI - Effect of parecoxib pretreatment and venous occlusion on propofol injection pain: a prospective, randomized, double-blinded, placebo-controlled study. AB - STUDY OBJECTIVE: To investigate the effect of parecoxib pretreatment with venous occlusion on propofol injection pain. DESIGN: Prospective, randomized, double blinded, placebo-controlled study. SETTING: Operating room of a tertiary-care medical center. PATIENTS: 150 ASA physical status I patients scheduled for elective surgery. INTERVENTIONS: Patients were randomized to three groups of 50 patients each to receive pretreatment with normal saline (Group NS), parecoxib 20 mg (Group P20), or parecoxib 40 mg (Group P40). All groups underwent venous occlusion for two minutes before propofol was injected. All pretreatment drugs were prepared in 5 mL doses. MEASUREMENTS: Pain scores were obtained by a study blinded observer during propofol injection following the different pretreatment solutions. MAIN RESULTS: Pain scores among the three groups were significantly different (P < or = 0.001). In Group NS, 29 (58%) patients had pain during propofol injection compared with 22 (40%) Group P20 and 13 (26%) Group P40 patients (P < or = 0.005). Pain was significantly reduced in Group P40 (P < or = 0.001) compared with the control group. Moderate to severe pain was experienced by 18 (36%) Group NS and 4 (8%) Group P20 patients, whereas no Group P40 patient experienced moderate or severe pain (P < 0.001). Reduction in pain severity was statistically significant after pretreatment with either parecoxib 20 mg (P = 0.002) or parecoxib 40 mg (P < 0.001). CONCLUSION: Parecoxib 40 mg with venous occlusion is effective in reducing the frequency and severity of pain with propofol injection. Pretreatment with 20 mg of parecoxib reduces the severity of propofol injection pain significantly but does not reduce frequency compared with the control group. PMID- 20304349 TI - Wire-guided catheter exchange after failed direct laryngoscopy in critically ill adults. AB - STUDY OBJECTIVE: To describe a technique for tracheal intubation after failed direct laryngoscopy using a Laryngeal Mask Airway (LMA) to secure the airway and to establish ventilation, and as a conduit for fiberoptic intubation utilizing a pre-packaged, convenient, and commercially available wire-guided catheter exchange kit. DESIGN: Retrospective case series. SETTING: University hospital. MEASUREMENTS: The cases of 5 critically ill adult patients who required intubation for respiratory failure, and in whom direct laryngoscopy was unsuccessful and unanticipated, were reviewed. Difficult intubation was defined as > or = two attempts by direct laryngoscopy and use of an airway adjunct/alternate airway device, or > or = three attempts by direct laryngoscopy. Occurrence of hypotension, hypoxemia, and the time required to accomplish the intubation were recorded. MAIN RESULTS: Patients' tracheas were intubated in the emergency department (n = 2), the intensive care unit (n = 2), and the radiology department (n = 1). An Eschmann endotracheal tube (ETT) introducer was used in 4 of the 5 patients, and a GlideScope was used in the fifth patient. After failed direct laryngoscopy, an LMA Classic was inserted to gain an airway, after which a fiberoptic bronchoscope and wire-guided catheter exchange set was used to change the LMA to a conventional ETT. Ventilation was maintained via the LMA with an attached bronchoscope adapter throughout the procedure. CONCLUSIONS: In all 5 patients, the trachea was successfully intubated within three minutes on the first attempt, using a wire-guided exchange, without hypoxemia or hypotension. PMID- 20304350 TI - Comparison of cardiac output as assessed by transesophageal echo-Doppler and transpulmonary thermodilution in patients undergoing thoracic surgery. AB - STUDY OBJECTIVE: To evaluate the accuracy of cardiac index (CI) as measured by echo-transesophageal Doppler monitoring (echo-TDM) with CI measured by the transpulmonary thermodilution technique. DESIGN: Prospective, observational study. SETTING: University hospital. PATIENTS: 16 patients scheduled for elective lung cancer resection. INTERVENTIONS: Patients underwent two-lung ventilation (TLV) and one-lung ventilation (OLV). MEASUREMENTS AND MAIN RESULTS: CI measurements were analyzed using Bland-Altman plots. Absolute values of CI as measured by both devices were highly correlated (r(2) ranging from 0.72 to 0.77), as were relative changes in CI after the start of OLV (r(2) = 0.48, P = 0.006). Before, during, and after OLV, TDM-CI biases were 0.46 +/- 0.28 L/min/m(2), 0.25 +/- 0.18 L/min/m(2), and 0.35 +/- 0.29 L/min/m(2), respectively. Limits of agreement remained stable throughout the three measurement periods (range -1.08 to 0.21 L/min/m(2)). The mean percentage error of CI measurements was 21.9% compared with the thermodilution technique. Although no adverse events were reported, 11% of measurement sets were incomplete due to poor signal detection. CONCLUSIONS: Echo-TDM is a safe technique, allowing continuous semi-invasive assessment of hemodynamic changes in most patients undergoing open-chest surgery. Doppler-derived CI values showed significant biases and moderate clinical agreement with transpulmonary thermodilution during TLV and OLV. PMID- 20304351 TI - How far can we go with positive end-expiratory pressure (PEEP) in liver transplant patients? AB - STUDY OBJECTIVE: To assess the effect of positive end-expiratory pressure (PEEP) up to 15 cm H(2)O on blood flow throughput of the liver and its effects on systemic hemodynamics in patients following liver transplantation. DESIGN: Prospective, interventional study. SETTING: Intensive care unit (ICU) of a university hospital. PATIENTS: 74 consecutive liver transplant recipients with a regular allocated cadaveric graft. INTERVENTION: The lungs of all study patients were postoperatively mechanically ventilated with biphasic positive airway pressure. Three different PEEP levels (5, 10, and 15 cm H(2)O) were randomly set within 4 hours of admission to the ICU. Systemic hemodynamic parameters were recorded using a pulmonary artery catheter and flow velocities were measured of the hepatic artery, portal vein, and right hepatic vein using a Doppler. MEASUREMENTS AND MAIN RESULTS: PEEP of 15 cm H(2)O induced a significant increase in central venous pressure and pulmonary capillary wedge pressure versus PEEP 5 cm H(2)O. Flow velocities of the right hepatic vein, portal vein, and hepatic artery were not influenced by PEEP. There also was no impact of increased PEEP on mean arterial pressure or cardiac index. CONCLUSION: PEEP up to 15 cm H(2)O does not impair liver outflow or systemic hemodynamics in liver transplant patients. PMID- 20304352 TI - The effect of warmed ropivacaine to body temperature on epidural sensory block characteristics. AB - STUDY OBJECTIVE: To determine whether warmed (body temperature) ropivacaine increases the speed of onset of sensory block of epidural anesthesia. STUDY DESIGN: Prospective, randomized, double-blind study. SETTING: University hospital. PATIENTS: 180 ASA physical status I and II patients, aged 18 to 64 years, undergoing elective anal surgery. INTERVENTIONS: Patients were randomly divided into 6 groups defined by ropivacaine temperature [room temperature (RT) or body temperature (BT)] and concentration (0.5%, 0.75%, or 1.0%). MEASUREMENTS: Sensory block was evaluated by pinprick at the T10, T12, L3, and the perianal region (S4, S5) dermatomes. pH values and adverse events were also recorded. MAIN RESULTS: There were no differences in baseline demographics, pH, or upper sensory level between groups. Mean onset time of T12 and L3 sensory block was significantly faster for each BT than RT ropivacaine concentration. Anal region (S4, S5) sensory block was significantly faster after BT 0.75% versus RT 0.75% ropivacaine. CONCLUSIONS: Warmed ropivacaine shortens the onset of sensory block of epidural anesthesia. PMID- 20304353 TI - Factors impacting on-time transfer to the operating room in patients undergoing peripheral nerve blocks in the preoperative area. AB - STUDY OBJECTIVES: To assess the on-time transfer to the operating room (OR) when peripheral nerve blocks (PNBs) are performed prior to surgery. DESIGN: Prospective time motion study. SETTING: Preoperative area of a university medical center. PATIENTS: 650 candidates for PNBs for postoperative analgesia. INTERVENTION: Patients were allocated to two groups: a control group (no PNB performed) and a PNB group (PNBs performed). MEASUREMENT TIME: The time required to perform each of the steps leading to transfer to the OR was recorded. MAIN RESULTS: On-time transfer was achieved in 40% and 49% in the blocked (n = 549) and control groups (n = 101), respectively (P = 0.067, one-sided). Surgery related delays represented the most important causes of delays (51.9% in the control group and 53.8% in the PNB group). The average time required to perform the blocks was 21 minutes (20-22 min). This time varied with the type and number of blocks performed (12-30 min). Performing PNBs accounted for 15.1% of delays. CONCLUSIONS: Performing PNBs prior to surgery in the preoperative area takes additional time. This time needs to be considered in optimizing on-time transfer to the OR. PMID- 20304354 TI - Study of the anatomical position of the femoral nerve by magnetic resonance imaging in patients with fractured neck of femur: relevance to femoral nerve block. AB - STUDY OBJECTIVE: To determine the anatomical location of the femoral nerve in patients who have sustained fracture of the neck of femur, and its relevance to femoral nerve block technique. DESIGN: Prospective, observational clinical study. SETTING: Orthopedic and Radiology departments of a regional hospital. SUBJECTS: 10 consecutive adult ASA physical status II and III patients (mean age, 78.5 yrs) and 4 adult healthy volunteers. INTERVENTIONS: A T1 magnetic resonance imaging scan was performed of both upper thighs in patients and healthy volunteers successfully. MEASUREMENTS: The distance (mm) between the midpoint of the femoral artery and the midpoint of the femoral nerve, and the distance of the femoral nerve from the skin was measured at the mid-inguinal ligament, the pubic tubercle, and at the mid-inguinal crease. Data are shown as means (SD). Differences between both sides were compared using paired Student's t-tests. P < 0.05 was significant. MAIN RESULTS: In patients the mean distance (mm) between the midpoint of the femoral nerve from the midpoint of femoral artery at the mid inguinal crease on the fractured and non-fractured sides was 10.7 and 11.0, respectively (P = 0.87). The mean distance (mm) between the midpoint of the femoral nerve from the midpoint of the femoral artery at the mid-inguinal ligament on the fractured and non-fractured sides was 9.64 and 12.5, respectively (P = 0.03). The mean distance (mm) between the midpoint of the femoral nerve from the midpoint of the femoral artery at the pubic tubercle on the fractured and non fractured sides was 8.74 and 10.49, respectively (P = 0.18). CONCLUSIONS: Blockade of the femoral nerve may be easier to perform at the mid-inguinal crease in patients with fractured neck of femur. PMID- 20304355 TI - Dexmedetomidine and magnesium sulfate in the perioperative management of a child undergoing laparoscopic resection of bilateral pheochromocytomas. AB - The case of an 8 year-old boy undergoing resection of pheochromocytoma, who received a combination of dexmedetomidine and magnesium sulfate (MgSO4) for hemodynamic control, is reported. He was prepared for surgery with phenoxybenzamine and atenolol. Dexmedetomidine was started in the preoperative holding area and, with MgSO4, continuously infused for most of the case. Good cardiovascular stability was achieved, but low-dose esmolol and nicardipine infusions were required during tumor manipulation. There was minimal post resection hypotension, the neuromuscular block was easily antagonized, and the child's trachea was quickly extubated. PMID- 20304356 TI - Treating stridor with opioids: a challenging case of paradoxical vocal cord movement. AB - A 61 year-old patient with a history of anxiety disorder presented with stridor after an uneventful laparotomy with a general anesthetic. Postoperative analgesia was withheld secondary to intermittent oxygen desaturation. She was unresponsive to standard therapies, including racemic epinephrine and albuterol nebulizers. An otolaryngology consultant performed fiberoptic laryngoscopy and paradoxical vocal cord movement was diagnosed. When fentanyl was subsequently administered to treat her pain, the stridor resolved. PMID- 20304357 TI - Severe hypotension after interscalene block for outpatient shoulder surgery: a case report. AB - The case of a 43 year-old woman who underwent successful right interscalene brachial plexus block for arthroscopic shoulder surgery is presented. During the surgery, she subsequently exhibited signs of neuraxial spread of local anesthetic. Bilateral motor block was noted postoperatively. Spontaneous ventilation was maintained throughout the case, and she was successfully discharged home several hours after the procedure with no residual symptoms. PMID- 20304358 TI - Continuous cervical paravertebral catheter knot. AB - The case of a 67 year-old woman who underwent left rotator cuff repair with subacromial decompression and acromioplasty with general anesthesia and a posterior cervical paravertebral catheter for postoperative pain control is presented. The catheter was placed without apparent incident and appropriate neural block and analgesia were achieved. On attempted removal of the catheter, resistance was encountered and a knot in the catheter was identified. Imaging showed no entanglement of nerve or vascular structures. Using a small skin incision, the catheter was successfully removed. PMID- 20304359 TI - Accidental cross-clamping of the superior vena cava: management and BIS evolution. AB - The case of a 38-year old man with recurrent adenocarcinoma of the right lung and infiltration of the thoracic wall, who underwent a right pneumonectomy with thoracic wall resection, is described. Dissection of the right pulmonary hilous was extremely difficult due to the previous operations. The superior vena cava (SVC) was accidentally ligated, resulting in profound hypotension and increased venous pressure in the internal jugular vein. Immediate blood aspiration through a 8.5-French introducer sheath lowered the venous congestion. After the SVC was cross-clamped, the Bispectral Index (BIS) acutely decreased to 0 and remained low during the resuscitation. Over the next 5 hours, BIS was directly affected by mean arterial pressure. Four days postoperatively, the patient was neurologically intact. PMID- 20304360 TI - A strategy to prevent substance abuse in an academic anesthesiology department. AB - Substance abuse is the most serious occupational safety issue associated with the practice of anesthesiology, with an incidence as high as 1% per year of training. The Cleveland Clinic's Anesthesiology Institute approached the process from the perspective of active prevention, including specific mandatory education programs for all department personnel on a recurring basis, strengthened procedures for the detection and prevention of diversion of controlled substances, enhanced skill building for detection of impairment, and implemented a multi-faceted drug testing program, including random and "for cause" urine screens, for prevention and early detection of abused anesthetic drugs and other substances of abuse. After 18 months of preparation, a Substance Abuse Prevention Protocol was created, which has been fully implemented as of September 1, 2007. PMID- 20304361 TI - Interscalene block should be a block for shoulder and proximal humerus surgery, and nothing else. PMID- 20304363 TI - Maneuvers to prevent oropharyngeal injury during orotracheal intubation with the GlideScope video laryngoscope. PMID- 20304364 TI - Anesthesia with the ProSeal Laryngeal Mask Airway for a patient with Mounier-Kuhn syndrome. PMID- 20304365 TI - The value of the P-value. PMID- 20304366 TI - [Analysis of the selection process for new drugs in a tertiary hospital 2004 2007]. AB - OBJECTIVE: The purpose of this study is to describe the structure of the CFyT, the Pharmacy and Therapeutics Committee, and a tertiary hospital's selection process for new drugs. MATERIAL AND METHODS: All annals of the P&TC and the New Drug Incorporation Guides (GINF) to incorporate new drugs received at Hospital Virgen del Rocio between 2004 and 2007 were reviewed. We carried out a descriptive study which collected variables having to do with the drug (drug type, type of register, route of administration and legal category), the petitioner (responsible division, professional category and request type) and the result of the evaluation (final decision, elapsed time between the request and the decision). RESULTS: Of the 72 requested drugs, 45 (62.5%) were approved: six as equivalent treatments, 36 (80%) with specific recommendations, and three (4.2%) with no restrictions. Twelve drugs (81.1%) were not included due to insufficient evidence of their effectiveness compared with the current treatment. The most frequently-requested drug type was the antineoplastics, most commonly requested by Oncology and Haematology divisions. We highlight the fact that many of the petitioners included clinical trials (97.2%) and data referring to costs (84.7%). CONCLUSIONS: There is a high level of compliance with the GINF guide in our centre, which guarantees that the P&TC's final decision is based on scientific evidence. PMID- 20304367 TI - [Optimisation of a high-efficiency liquid chromatography technique for measuring lamotrigine in human plasma]. AB - OBJECTIVE: The purpose of this study was to optimise the HPLC-UV bio-analytical method currently used by the Salamanca University Clinical Hospital for determining lamotrigine plasma levels. MATERIAL AND METHODS: The developed HPLC UV analytic technique currently in use was shown to be linear, exact and precise, and suitable for use in routine monitoring of lamotrigine levels. The drawback of this method has always been the time required for analysing samples, so our aim was to improve on that elapsed time. That improvement involved using a different chromatographic column from the one used up until now. We replaced the column that was normally used (Kromasil-100C18-5 microm-15*0.4 cm with a LiChroCART RP18e-3 microm-5.5*0.4 cm); in both cases, a liquid-liquid extraction was performed and the same sample extraction protocol was followed. RESULTS: Both validation methods showed that the two column types are valid for routine lamotrigine monitoring. CONCLUSION: The decrease in retention time, in addition to a lower quantification limit and better precision and accuracy parameters obtained with the LiChorCART column, suggest that this unit is ideal for use in clinical practice because it enables a large number of determinations to be performed in less time and the greater precision of LTG measurements. PMID- 20304368 TI - [Protocol for inducing infliximab tolerance in a patient with psoriatic spondylarthritis]. PMID- 20304369 TI - [Preventing potential medication errors in mobile emergency units]. PMID- 20304370 TI - [Effectiveness and safety of rituximab in pemphigus vulgaris]. PMID- 20304371 TI - [Rhabdomyolysis and metabolic acidosis associated with propofol use]. PMID- 20304372 TI - [Dabigatran in the treatment of a morbidly obese patient with recurring venous thrombosis]. PMID- 20304373 TI - Improving the education of the nursing workforce: a landmark study from the Carnegie foundation. PMID- 20304374 TI - A necessary sea change for nurse faculty development: spotlight on quality and safety. AB - More than 10 years have passed since the publication of the Institute of Medicine's report, To Err is Human: Building a Safer Health Care System, yet recent reports indicate that significant strides toward transformational improvement in quality and patient safety are still necessary. Real progress toward superior health care quality requires foundational enhancements in health care education. An urgent need exists for undergraduate nursing programs to strengthen quality and safety knowledge in their curricula. A first step in attaining this goal is to equip baccalaureate nursing faculty with the knowledge, skills, and abilities needed to teach these concepts. The first part of this article provides a compelling case for new graduate nurses to have a comprehensive understanding of how quality and safety issues affect patient outcomes. The second part highlights the specific faculty competencies required to teach quality and safety to undergraduate nursing students and offers a framework that faculty can use for professional development in this area. This article is by no means exhaustive but provides a starting point for providing undergraduate nursing faculty with the knowledge, skills, and attitudes necessary to assist students to achieve quality and safety competencies in their curricula. PMID- 20304375 TI - How do future nursing educators perceive informatics? Advancing the nursing informatics agenda through dialogue. AB - Informatics is a popular topic in literature, in media, and in education. However, nursing professionals and even nursing faculty may not have a clear understanding of informatics. The authors conducted a small simulation study to examine how nursing students enrolled in a doctor of philosophy program-future nursing educators-perceived informatics and its core elements. Using an online collaboration tool, the students were asked to create a plan for integrating informatics into a simulated undergraduate nursing program. The results of the study provide lessons for nursing professionals and educators. Students identified only a handful of competencies believed important by informatics initiatives led by the American Nurses Association and the Technology Informatics Guiding Education Reform. Although most students believed an undergraduate curriculum should teach computer skills, only a few participants identified information literacy skills, such as privacy and security of health information, as important for beginning nurses. Although limited, findings articulate the need for a universally accepted definition of informatics and a shared understanding of an informatics core curriculum. PMID- 20304376 TI - Making time: moving the faculty dossier to an electronic format. AB - With the shortage of nursing faculty comes the challenge of an increasing workload and the competing demands for time required for teaching, service, and scholarship. Faculty must demonstrate their excellence in each of these areas as they prepare dossiers for annual reviews, tenure, and promotion. This article explores how technology can help faculty find additional time to achieve the expectations of higher education and establish an ongoing repository of faculty data and documentation. To accomplish this, the authors designed a faculty electronic dossier (e-dossier), using Blackboard technology to replace the traditional paper dossier. This article describes the process of designing the faculty e-dossier and presenting it to the faculty and administrators and discussing the acceptance of this innovative change. The authors use Rogers' (Rogers E. (1983). Diffusion of innovation (3rd ed.) (rev.ed.) London: The Free Press.) diffusion of innovation theory to understand why faculty were more accepting of this innovation than were administrators and how to address this difference. PMID- 20304377 TI - Factors related to progression and graduation rates for RN-to-bachelor of science in nursing programs: searching for realistic benchmarks. AB - Measurement and analysis of progression and graduation rates is a well established activity in schools of nursing. Such rates are indices of program effectiveness and student success. The Commission on Collegiate Nursing Education (2008), in its recently revised Standards for Accreditation of Baccalaureate and Graduate Degree Nursing Programs, specifically dictated that graduation rates (including discussion of entry points, timeframes) be calculated for each degree program. This context affects what is considered timely progression to graduation. If progression and graduation rates are critical outcomes, then schools must fully understand their measurement as well as interpretation of results. Because no national benchmarks for nursing student progression/graduation rates exist, schools try to set expectations that are realistic yet academically sound. RN-to-bachelor of science in nursing (BSN) students are a unique cohort of baccalaureate learners who need to be understood within their own learning context. The purposes of this study were to explore issues and processes of measuring progression and graduation rates in an RN-to BSN population and to identify factors that facilitate/hinder their successful progression to work toward establishing benchmarks for success. Using data collected from 14 California schools of nursing with RN-to-BSN programs, RN-to BSN students were identified as generally older, married, and going to school part-time while working and juggling family responsibilities. The study found much program variation in definition of terms and measures used to report progression and graduation rates. A literature review supported the use of terms such as attrition, retention, persistence, graduation, completion, and success rates, in an overlapping and sometimes synonymous fashion. Conceptual clarity and standardization of measurements are needed to allow comparisons and setting of realistic benchmarks. One of the most important factors identified in this study is the potentially prolonged RN-to-BSN timeline to graduation. This underlines the need to look beyond standardized educational norms for graduation rates and consider the realities of "persistence" by which these students are successful in completing their studies. It also raises the question of whether student success and program success/effectiveness are two separate measures or two separate events on one progression timeline. While clarifying our thinking about success in this population of students, the study raised many questions that warrant further research and debate. PMID- 20304378 TI - Influence of work role and perceptions of climate on faculty organizational commitment. AB - The purpose of this study was to examine how organizational commitment is influenced by organizational climate and nurse faculty work role in departments/colleges of nursing. The research was based on Meyer and Allen's Multidimensional Model of Organizational Commitment. The sample was comprised of full-time tenure track, doctorally prepared nurse faculty. Descriptive analyses were used to summarize institutional and nursing program data. ANOVA and t-tests were performed to determine differences between faculty information and study variables. A significant difference was found between teaching work role, and role ambiguity, role conflict and organizational climate. Pearson correlation analyses examined relationships between nurse faculty work role balance, role ambiguity, role conflict, and affective, continuance, and normative organizational commitment. A moderately strong negative relationship was present between role ambiguity and role conflict, and affective and continuance organizational commitment. Significant relationships were observed between subscales of organizational climate and role ambiguity and role conflict. The study's findings offer interesting insights into the dynamic relationships between organizational commitment and climate, work role balance, role ambiguity, and role conflict. PMID- 20304379 TI - Adjunct faculty development: reported needs and innovative solutions. AB - One strategy for solving the nursing shortage is to increase the enrollment in undergraduate programs in schools of nursing. However, the shortage of full time faculty may prohibit larger enrollments. Employing adjunct faculty is one way to meet the teaching demands of increasing enrollment. Hiring and retaining qualified adjunct faculty is a challenge faced by many schools of nursing. To maintain quality, schools must meet the development needs of this unique group of faculty. Job satisfaction of adjunct faculty influences retention. Limited published research addresses the development needs of adjunct nursing faculty. This article describes the findings from a survey designed to identify the overall needs of our adjunct faculty. Based on the survey's findings, several new initiatives were implemented with the ultimate aim of retaining a cadre of qualified teachers. PMID- 20304380 TI - Dying with dignity in America: the transformational leadership of Florence Wald. AB - The aims of this study are to examine the constructs of transformational leadership as they played out for one nurse who steered significant change in the care of the dying in the United States and to provide deeper insights into how nursing leaders can design and direct meaningful changes in the delivery of health care in turbulent times. A significant problem was identified in how the terminally ill were treated in this country post World War II. The introduction of hospice care in the United States represented a paradigm shift in how the health care community viewed and treated dying patients. Critical to this transformation was the work of Florence Wald, who organized with community leaders, clergy, and other health care providers to create a vision and synergy around palliative care. She was instrumental in opening the first American hospice in 1971 in Connecticut. Within 15 years, there were more than 1,000 hospices in the United States. A single case study design was chosen for this qualitative research grounded in the theory of transformational leadership (J.M. Burns, 1978). The study used narrative inquiry to conduct an in-depth exploration of Florence Wald's transformational leadership and the perceptions of the group of founders she organized to conceptualize, build, and open the first hospice in the United States. The participants chosen for interview were involved directly in the designing, planning, and beginning of the first American hospice. In addition to the seven in-depth interviews conducted in 2007 in Connecticut, this research examined three groups of documents from The Florence and Henry Wald Archives in the Yale University Library. The findings from both interviews and the Yale Archives showed that Florence Wald based her leadership on the strong values of reverence for life and social justice for all. To direct meaningful change, Florence Wald elevated the consciousness of her hospice team by conducting a 2-year research study on the needs of dying patients to ensure interventions were based on evidence. To encourage a high level of participation, Florence Wald demonstrated a caring component in her leadership with a strong commitment to mentoring. Wald worked to transform the quality of end-of-life care by assessing the readiness for change prior to acting and by working to provide supports for success. Finally, the findings showed that Florence Wald built consensus on vision before executing purposeful change by collaborating with the Founders and asking the hard questions to examine standards of care. Florence Wald provided transformational leadership in creating a value-driven culture of inquiry among the Founders where decision making was evidence-based and significantly improved the quality of palliative care in the United States. Nursing leaders who build upon the shared values to provide direction and promote momentum critical to the change will have more success in reaching strategic outcomes of transformational efforts. Transformational nursing leaders who build consensus on vision before executing purposeful change by collaborating with a wide group of stakeholders will encourage a broader ownership of the change. When nursing leaders work to elevate the consciousness of their work groups to direct meaningful change by developing and sustaining value-driven cultures of inquire, decisions will more directly align with evidence and support successful outcomes. PMID- 20304381 TI - [The return to life with insulin]. AB - The Canadian Frederick Banting (1891-1941), in discovering the existence of insulin, was able to treat, for the first time, with efficiency, diabetic patients. This discovery and its application did not happen easily, in particular within his own team. In 1922, the Nobel Prize would reward this researcher, who died two decades later in an airplane crash. PMID- 20304382 TI - Influence of saliva substitute films on the initial adhesion of Candida albicans to dental substrata prior to and after artificial ageing. AB - OBJECTIVE: The aim of this in vitro study was to investigate whether saliva substitute films influence the adhesion of Candida albicans to different dental substrata prior to and after artificial ageing. DESIGN: Specimens of a denture base resin (DB) and a veneering composite (VC) were polished and subjected to an artificial ageing protocol (thermal cycling, 2 x 3000 cycles 5/55 degrees C). Bovine enamel (BE) and glass were used as reference materials. After determination of surface free energy, specimens were rinsed with commercial saliva substitutes (Aldiamed, Saliva natura, Saliva Orthana, Salinum), a positive control (protein mixture), or a negative control (Phosphate Buffered Saline, PBS) for 2h at 37 degrees C in a flow chamber. Specimens were then exposed to a C. albicans ATCC 10231 suspension for 4h at 37 degrees C. Adherent, viable Candida cells were quantified using a luminometric ATP-based assay. Statistical analysis was performed using 1- and 2-way ANOVA, and post-hocs were analysed using the Tukey-Kramer test (alpha<.05). RESULTS: Our data indicated that VC (31.1 mJ/m2) and DB (33.9 mJ/m2) yielded the lowest surface free energy prior to artificial ageing, and BE (43.6 mJ/m2) yielded the highest surface free energy. For C. albicans adhesion, both the materials as well as the saliva substitutes influenced relative luminescence intensities, indicating significant differences in C. albicans adhesion between the various materials and after treatment with the saliva substitutes. CONCLUSIONS: Saliva substitutes may have a decisive influence on C. albicans adhesion, but their impact appears to be dependent on the properties of the underlying substratum material. PMID- 20304383 TI - Trained interpretive bias survives mood change. AB - Evidence is accumulating that interpretations can be trained using Cognitive Bias Modification procedures (CBM). The effects are replicable, stable over time and there is some evidence of generalizability. As a next step in determining the boundaries of the CBM model, the present experiment was designed to test whether modified interpretive style endures fluctuations in mood. Participants were trained to interpret ambiguous scenarios in either a positive (n = 42) or negative (n = 40) way. Then, participants were exposed to either a positive (n = 41) or negative (n = 41) mood induction procedure to change their current mood state. Results showed that the modified interpretive bias did not change in reaction to a mood change. That is, differences in interpretation of new ambiguous information were related to the interpretive bias modification procedure and not to the current mood state. PMID- 20304384 TI - Factor structure of the Dutch version of the Penn State Worry Questionnaire. AB - The Penn State Worry Questionnaire (PSWQ) is a 16-item self-report scale for measuring the excessiveness and uncontrollability of worry. The current study examined the factor structure of the PSWQ in (1) a large community sample (N = 455), and (2) a clinical sample of patients with generalized anxiety disorder (GAD; N = 102), the disorder for which worry is the key feature. Confirmatory factor analysis was employed to test three models: (1) a one-factor model in which all items loaded on one and the same dimension, (2) a two-factor model in which positively and negatively worded items loaded on two separate but correlated factors, and (3) a one-factor model, that included the reverse items as a method factor. In the community sample the one-factor/method factor model provided the best fit for the data. This was also true in the clinical GAD sample, but only after error covariances between a number of items were allowed to correlate. PMID- 20304386 TI - Direct chemical glycosylation with pentenyl- and thioglycoside donors of N acetylglucosamine. AB - The use of pentenyl and thiophenyl glycosides of N-acetylglucosamine (GlcNAc) as glycosyl donors for the direct preparation of O-glycosides of GlcNAc promoted by N-iodosuccinimide (NIS) and metal triflates in dichloromethane has been investigated. Both glycosyl acceptors 1-octanol and (-)-menthol resulted in good glycosylation yields for both types of donors with pentenyl glycosides being somewhat superior in terms of yield. Carbohydrate-based acceptors were reacted with a benzylated GlcNAc-pentenyl donor but only provided disaccharides in poor to moderate yields. The results show that a variety of metal triflates are capable of acting as an activator for both NIS and the intermediate oxazoline. PMID- 20304385 TI - A preliminary investigation of sudden gains in exposure therapy for PTSD. AB - The purpose of the current study was to examine sudden gains in those receiving treatment for PTSD and whether these rapid changes were related to overall symptom reduction in a small sample of female assault survivors with PTSD undergoing prolonged exposure (PE) therapy. Sudden gains were found to occur in 52% of the sample. Among those who experienced a sudden gain, the average magnitude (12.4 points) accounted for 61% of overall symptom reduction. Importantly, treatment outcome was better for those who experienced sudden gains than those who did not. The experience of a sudden gain may result in patients becoming more fully engaged with treatment, and recognition of them may result in identifying potential process-related predictors of treatment response. PMID- 20304387 TI - Iodine-hexamethyldisilane (HMDS)-mediated anomerization of peracetylated 1,2 trans-linked alkyl and aryl glycosides. AB - Treatment of peracetylated alkyl and aryl 1,2-trans-glycosides with iodine in the presence of HMDS has been found to result in the anomerization leading to the formation of the respective 1,2-cis-glycosides. In the case of alkyl glycosides with aglycons of short alkyl chain length complete anomerization to the alpha glycosides was observed while with those of longer chain length the process was found to be incomplete. The observations have been interpreted mechanistically. PMID- 20304388 TI - Anti-human very late antigen-alpha4 (CD49d) monoclonal antibody (BU49) cross reacts with the canine B-cell leukemia cell line GL-1, resulting in the induction of homotypic cell aggregation. AB - We have found that the anti-human very late antigen-alpha4 (VLA-alpha4) (CD49d) monoclonal antibody (mAb) BU49 cross-reacts with the canine B-cell leukemia cell line GL-1. Interestingly, the BU49 mAb specifically induced the homotypic cell aggregation of GL-1 cells accompanied by morphological changes. Homotypic cell aggregates induced by BU49 mAb were blocked by the presence of a protein kinase C inhibitor, a protein kinase A inhibitor, an actin filament formation inhibitor, and an EDTA. On the other hand, a protein tyrosine kinase inhibitor, a DNA synthesis inhibitor, and an anti-canine CD45 mAb did not affect the GL-1 homotypic cell aggregation induced by BU49 mAb. The BU49 mAb immunoprecipitated at a molecular weight of about 150kDa in the GL-1 cells, similar to the results in the human monocyte-like cell line U937. Taken together, our results provide the first evidence that human CD49d recognized by BU49 mAb has unique immunological functions against canine cells. PMID- 20304389 TI - [Pain in right iliac fossa]. PMID- 20304390 TI - A new method to evaluate the elastic modulus of cortical bone by using a combined computed tomography and finite element approach. AB - This study attempted to estimate the elastic modulus of cortical specimens directly from the computed tomography (CT) number (CT). Cubic specimens of fresh bovine femora were tested under compressive loading. The corresponding three dimensional mesh models of these specimens were established with the aid of CT images. The elastic modulus of each element was determined using the following transfer formula: E=Ax(CT)(B). The A and B were determined by matching the simulation results with the experimental force-displacement curves. An optimization approach was used to match the entire specimen sets between simulations and experiments. The results indicated that the elastic modulus of cortical bone can be effectively estimated using a power relationship (E=1.26 x 10(-3) x (CT)(1.93)) directly from the CT number. This procedure eliminates the need to determine the bone density, and therefore reduces the computational time required to define mechanical properties in finite element methods. PMID- 20304391 TI - [Prognostic value of occult renal failure in the acute coronary syndrome]. PMID- 20304392 TI - Negative capsule endoscopy without subsequent enteroscopy does not predict lower long-term rebleeding rates in patients with obscure GI bleeding. AB - BACKGROUND: Capsule endoscopy (CE) is now widely accepted as a first-line diagnostic modality for obscure GI bleeding (OGIB). However, the clinical implications of negative results of CE studies remain unclear. OBJECTIVE: To investigate long-term (>1 year) outcomes for patients undergoing CE for OGIB and to identify risk factors associated with rebleeding. DESIGN AND SETTING: Retrospective study in a tertiary care hospital. METHODS: A total of 57 consecutive patients who had undergone CE for OGIB were enrolled and their pre- and post-CE clinical data were collected. Specific treatments were defined as treatments directly aimed at presumed bleeding causes including hemostasis and disease-specific medical therapy, whereas nonspecific treatments were defined as symptomatic treatments for anemia. RESULTS: Of the 57 patients, the indication for CE was obscure-overt bleeding in 46 patients and obscure-occult bleeding in 11 patients. Among 51 patients for whom long-term data were available, significant (P2) lesions were found in 23 (45.1%) patients. The overall rebleeding rate was 35.3% during a median follow-up duration of 31.7 months (range 12.8-58.0 months). There was no statistically significant difference in the cumulative rebleeding rate between patients with positive and negative CE results (34.8% vs 35.7%, respectively; P = .989). However, specific treatments after CE (hazard ratio, 0.111; 95% CI, 0.013-0.980; P = .043) significantly decreased rebleeding. LIMITATIONS: Small number of patients, retrospective study design. CONCLUSIONS: The rebleeding rate for patients with OGIB and negative CE results was substantial, indicating that these patients should be closely observed. However, specific treatment after CE significantly reduced the incidence of recurrent bleeding. PMID- 20304393 TI - Endoscopic treatment of a recalcitrant esophageal fistula with new tools: stents, Surgisis, and nitinol staples (with video). PMID- 20304394 TI - IgG4 immunostaining of duodenal papillary biopsy specimens may be useful for supporting a diagnosis of autoimmune pancreatitis. AB - BACKGROUND: Autoimmune pancreatitis (AIP) is now considered to be part of an immunoglobulin G4 (IgG4)-related systemic fibroinflammatory disease. OBJECTIVE: We evaluated whether IgG4 immunostaining of duodenal papillary biopsy specimens is useful for supporting a diagnosis of AIP. DESIGN: A prospective study. SETTING: A tertiary academic center. PATIENTS/INTERVENTIONS: We obtained 2 forceps biopsy specimens from the major duodenal papilla (MDP) of 19 symptomatic AIP patients during ERCP before steroid administration. As a control, biopsy specimens were obtained from the MDP of patients with pancreatic cancer (n = 35), cholangiocarcinoma (n = 20), ampullary cancer (n = 11), ordinary chronic pancreatitis (n = 18), and AIP in remission (n = 16) and immunohistochemically examined. MAIN OUTCOME MEASUREMENTS: Specimens were considered positive for IgG4 immunostaining if there were more than 10 IgG4-positive plasma cells per high power field. RESULTS: Positive IgG4 immunostaining of the MDP was found in 10 (53%) of 19 symptomatic AIP patients, but was absent in the control groups. Among symptomatic AIP patients (n = 19), 5 (83%) of 6 AIP patients with elevated serum IgG4 levels exhibited positive IgG4 staining of the MDP, whereas 5 (38%) of 13 AIP patients with normal serum IgG4 levels showed positive IgG4 staining of the MDP. Nine of 19 symptomatic AIP patients also underwent pancreatic biopsy, and positive IgG4 immunostaining of the MDP was observed in patients with positive pancreas IgG4 staining (4/6, 67%), but not in patients with negative pancreas IgG4 staining (0/3). LIMITATIONS: Small symptomatic AIP patient population. CONCLUSIONS: Positive IgG4 immunostaining of the MDP was an extremely specific and moderately sensitive tool for the diagnosis of AIP. IgG4 immunostaining of the MDP may be useful for supporting a diagnosis of AIP, especially when AIP is suspected clinically but serum IgG4 levels are normal or pancreatic tissue is not available. PMID- 20304395 TI - Optical coherence tomography for the staging of tumor infiltration in superficial esophageal squamous cell carcinoma. AB - BACKGROUND: Optical coherence tomography (OCT) is a noninvasive technology that can produce high-resolution cross-sectional images in real-time without acoustic coupling, enabling precise assessment of tumor invasion in superficial esophageal squamous cell carcinomas (SESCCs). OBJECTIVE: To elucidate the usefulness of in vivo OCT for the staging of SESCCs. DESIGN: A single-center, prospective study in 2 phases: phase I to establish the OCT criteria classified into 3 categories (epithelium or lamina propria mucosa [EP/LPM], muscularis mucosa [MM], submucosa [SM]) and phase II to evaluate these criteria. SETTING: An academic medical center. PATIENTS: Sixty-two patients with a histological diagnosis of SESCC by routine endoscopy. In the phase I study, 35 images from 16 patients were used. In the phase II study, 109 images from 46 subsequent consecutive patients enrolled from January 2007 to May 2009 were used. INTERVENTIONS: We performed OCT for preoperative staging followed by endoscopic submucosal dissection or a surgical procedure and compared precisely the visualized OCT sites with the corresponding tissue sections. MAIN OUTCOME MEASUREMENTS: The accuracy of OCT for the staging. RESULTS: The overall accuracy rate was 92.7% (EP/LPM, 94.9%; MM, 85.0%; SM, 90.9%). The OCT signal penetration depth was sufficient to depict the boundary of the deepest region of cancer, the thickness of which was less than 1.5 mm. LIMITATIONS: The small number of patients. CONCLUSIONS: To our knowledge, this is the first study demonstrating that OCT might be useful for the preoperative staging of SESCCs with a high degree of accuracy. PMID- 20304396 TI - Open-label, sham-controlled trial of an endoscopic duodenojejunal bypass liner for preoperative weight loss in bariatric surgery candidates. AB - BACKGROUND: The duodenojejunal bypass liner (DJBL) (EndoBarrier Gastrointestinal Liner) is an endoscopically placed and removable intestinal liner that creates a duodenojejunal bypass resulting in weight loss and improvement in type 2 diabetes mellitus. OBJECTIVE: Weight loss before bariatric surgery to decrease perioperative complications. DESIGN: Prospective, randomized, sham-controlled trial. SETTING: Multicenter, tertiary care, teaching hospitals. PATIENTS: Twenty one obese subjects in the DJBL arm and 26 obese subjects in the sham arm composed the intent-to-treat population. INTERVENTIONS: The subjects in the sham arm underwent an EGD and mock implantation. Both groups received identical nutritional counseling. MAIN OUTCOME MEASUREMENTS: The primary endpoint was the difference in the percentage of excess weight loss (EWL) at week 12 between the 2 groups. Secondary endpoints were the percentage of subjects achieving 10% EWL, total weight change, and device safety. RESULTS: Thirteen DJBL arm subjects and 24 sham arm subjects completed the 12-week study. EWL was 11.9% +/- 1.4% and 2.7% +/- 2.0% for the DJBL and sham arms, respectively (P < .05). In the DJBL arm, 62% achieved 10% or more EWL compared with 17% of the subjects in the sham arm (P < .05). Total weight change in the DJBL arm was -8.2 +/- 1.3 kg compared with -2.1 +/- 1.1 kg in the sham arm (P < .05). Eight DJBL subjects terminated early because of GI bleeding (n = 3), abdominal pain (n = 2), nausea and vomiting (n = 2), and an unrelated preexisting illness (n = 1). None had further clinical symptoms after DJBL explantation. LIMITATIONS: Study personnel were not blinded. There was a lack of data on caloric intake. CONCLUSIONS: The DJBL achieved endoscopic duodenal exclusion and promoted significant weight loss beyond a minimal sham effect in candidates for bariatric surgery. ( CLINICAL TRIAL REGISTRATION NUMBER: NPT00469391.). PMID- 20304397 TI - Endoscopic capsule placement improves the completion rate of small-bowel capsule endoscopy and increases diagnostic yield. AB - BACKGROUND: The methods for increasing the rate of complete small-bowel examinations by capsule endoscopy (CE) demonstrate conflicting results, and it is unknown whether improving the completion rate of CE transit is correlated with improvement in diagnostic yield. OBJECTIVE: The aim of this study was to determine whether a higher rate of complete small-bowel examinations results in a higher diagnostic yield of CE. DESIGN: Case-control comparison. SETTING: Tertiary care university hospital. PATIENTS: A total of 273 patients underwent conventional CE (group A), and 261 patients underwent real-time CE (group B). Furthermore, the patients in groups A and B were divided into 2 subgroups by pyloric transit time (A1, A2 and B1, B2, respectively). INTERVENTIONS: After swallowing the capsule, each patient was monitored with a real-time viewer in group B, and the patients underwent endoscopic placement if the capsule was delayed in the esophagus or stomach. MAIN OUTCOME MEASUREMENTS: Pyloric transit time, small-bowel transit time, the rate of complete small-bowel examinations, and the diagnostic yield. RESULTS: The rate of complete small-bowel examinations was significantly higher in group B than in group A (87.4% vs 78.0%, respectively; P = .004). The diagnostic yield was significantly higher in group B2 than in group A2 (60.0% vs 41.7%, respectively; P = .019). LIMITATIONS: Nonrandomized study. CONCLUSIONS: Endoscopic placement improves the rate of complete small-bowel examinations, resulting in a higher diagnostic yield of CE. PMID- 20304398 TI - Persistent snoring under conscious sedation during colonoscopy is a predictor of obstructive sleep apnea. AB - BACKGROUND: Obstructive sleep apnea (OSA) is characterized by cessation of breathing during sleep. Conscious sedation (CS) induces sleep and may uncover sleep-related breathing disorders. OBJECTIVE: To determine whether snoring during CS is a sensitive predictor of OSA. DESIGN: Matched cohort study. SETTING: University-based ambulatory endoscopy center. PATIENTS: Consecutive patients undergoing colonoscopy completed a detailed sleep questionnaire and physical examination geared toward detecting OSA (body mass index [BMI], neck circumference, and the presence of craniofacial abnormalities). The endoscopist was blinded to the information. INTERVENTIONS: Portable nocturnal polysomnography. MAIN OUTCOME MEASUREMENTS: Patients who snored during CS in the left lateral decubitus position for 10 seconds or longer were referred for polysomnography. Sex- and BMI-matched patients who did not snore served as control subjects. RESULTS: A total of 131 patients were enrolled, and 24 (18.3%) of them snored. These patients (22 men, 2 women) had a predominance of Mallampati grade III/IV, higher Stanford and Epworth scale scores, and greater BMI and neck circumference and were more likely to report daytime sleepiness, decreased vigilance, and personality and mood changes (all P values <.05). All investigated patients who snored during CS had evidence of OSA versus 4 of 18 control subjects (mean apnea-hypopnea index: 40 events vs 5 events; P < .0001) (100% positive predictive value; 77.8% negative predictive value). Moderate or severe OSA was detected in 14 of 20 patients versus 1 of 18 control subjects (P < .001; 70% positive predictive value; 94.4% negative predictive value, 93% sensitivity, 74% specificity). Data obtained from sleep questionnaires and physical examination failed to accurately predict OSA. LIMITATIONS: Single-center nature and relatively small number of patients developing the outcome variable. CONCLUSIONS: Snoring during CS is a strong predictor of OSA. Given the medical and financial burden of undiagnosed OSA, these patients should be carefully identified and referred for sleep medication evaluation. PMID- 20304399 TI - Endosonographic radial tumor thickness after neoadjuvant chemoradiation therapy to predict response and survival in patients with locally advanced esophageal cancer: a prospective multicenter phase ll study by the Swiss Group for Clinical Cancer Research (SAKK 75/02). AB - BACKGROUND: EUS response assessment in patients with locally advanced esophageal cancer undergoing neoadjuvant chemoradiation therapy (CRT) is limited by disintegration of the involved anatomic structures. OBJECTIVE: Predictive and prognostic values of a prospectively defined maximum tumor thickness (MTT). DESIGN: Prospective open-label phase ll study (SAKK 75/02). SETTING: Multicenter, nationwide. PATIENTS: Of 66 patients with primary CRT, 56 underwent en bloc esophagectomy. INTERVENTIONS: EUS-measured MTT before and 2-5 weeks after CRT (yMTT). MAIN OUTCOME MEASUREMENTS: Cutoffs: (1) absolute thickness (yMTT) after CRT < or = 6 mm; (2) relative reduction compared with baseline (ratio yMTT/MTT) < or = 50%. Correlation between EUS measurements and histopathologic tumor regression grade (TRG) and overall survival (OS). RESULTS: Sixteen of 56 patients were not included for EUS evaluation (10 severe stenosis, 5 MTT not measured, 1 intolerance to second EUS). Characteristics (n = 40) were as follow: median age, 60 years; squamous cell carcinoma, 42%; and adenocarcinoma (AC), 58%. Initial stage was: 10 T2N1, 3 T3N0, 26 T3N1, 1 T3Nx; 14 of 23 AC Siewert type 1. Wilcoxon rank sum test showed significant correlation of TRG1 with yMTT < or = 6 mm (P = .008) and yMTT/MTT < or = 50% (P = .003). The effect of yMTT on TRG1 was significant (P = .0193; odds ratio, 0.687 [95% CI, 0.502-0.941]). The predefined cutoff of < or = 6 mm for yMTT was predictive for TRG1 (P = .0037; Fisher exact test). After a median follow-up of 28.6 months, there was a clear trend for benefit in OS with yMTT < or = 6 mm and yMTT/MTT < or = 50%. LIMITATIONS: Small sample size. CONCLUSION: In a multicenter setting, MTT measured by EUS after CRT was highly predictive for response and showed a clear trend for predicting survival. PMID- 20304400 TI - Mature teratoma of the rectum. PMID- 20304401 TI - EUS for pancreatic neuroendocrine tumors: a single-center, 11-year experience. AB - BACKGROUND: Pancreatic neuroendocrine tumors (PNTs) are rare tumors with malignant potential. EUS and EUS-guided FNA (EUS-FNA) have been shown to be superior to other imaging methods in the preoperative localization and diagnosis of PNTs. OBJECTIVES: To evaluate the clinical presentation, EUS morphology, and sensitivity of EUS-FNA cytology in a large consecutive cohort with histologically and/or cytologically confirmed PNTs. DESIGN: Retrospective study of all consecutive patients from July 1995 to November 2006 who underwent EUS for a known or suspected PNT and had a subsequently histologically confirmed PNT. SETTING: Tertiary referral center. PATIENTS: Ninety-two patients with suspected PNT. INTERVENTIONS: EUS evaluation with or without EUS-FNA of PNTs. MAIN OUTCOME MEASUREMENTS: Clinical and EUS features of PNTs and sensitivity of EUS-FNA for the diagnosis of PNTs. RESULTS: Ninety-two patients underwent EUS; 76 patients had confirmed histopathology, of whom 69 (91%) were symptomatic. Patients with functional PNTs presented with diarrhea, peptic ulcer disease, and hypoglycemia. Tumor locations and echogenic features were similar except that nonfunctional PNTs tended to be larger and have cystic features. Patients with malignant PNTs were older (P = .03), presented with abdominal pain, and had larger tumors (P = .0006) with irregular margins. Eighty-nine percent of patients underwent EUS-FNA. Sensitivity of EUS-FNA for the diagnosis of a PNT was 87%. Sensitivity of EUS-FNA was similar in functional and nonfunctional PNTs. The sensitivity of EUS-FNA was higher for malignant PNTs (P = .008). LIMITATIONS: Retrospective single tertiary center. CONCLUSIONS: EUS and EUS-FNA are sensitive tools, especially in cases of suspected symptomatic PNTs in which other imaging modalities have failed. PMID- 20304402 TI - Endoscopic closure of a large ERCP-related lateral duodenal perforation by using endoloops and endoclips. PMID- 20304403 TI - Acute reversible gastroparesis and megaduodenum after botulinum toxin injection for achalasia. PMID- 20304404 TI - MIMO model of an interacting series process for Robust MPC via System Identification. AB - This paper discusses the empirical modeling using system identification technique with a focus on an interacting series process. The study is carried out experimentally using a gaseous pilot plant as the process, in which the dynamic of such a plant exhibits the typical dynamic of an interacting series process. Three practical approaches are investigated and their performances are evaluated. The models developed are also examined in real-time implementation of a linear model predictive control. The selected model is able to reproduce the main dynamic characteristics of the plant in open-loop and produces zero steady-state errors in closed-loop control system. Several issues concerning the identification process and the construction of a MIMO state space model for a series interacting process are deliberated. PMID- 20304405 TI - Multiclass, multiresidue method for the detection of antibiotic residues in distillers grains by liquid chromatography and ion trap tandem mass spectrometry. AB - The increased production of ethanol in the US has resulted in large amounts of distillers grains (DG) which is an excellent feed supplement for livestock. However, the use of antimicrobials during ethanol fermentation has led to a growing concern over the possibility of their residues remaining in DG. To enable the detection of antimicrobial residues, a robust LC-MS/MS method was developed that included 13 antibiotics of diverse chemistries, ampicillin, penicillin G, tetracycline, oxytetracycline, chlortetracycline, bacitracin A, virginiamycin M1, chloramphenicol, erythromycin A, clarithromycin, tylosin A, monensin A and streptomycin. The residues were extracted with an aqueous solution of EDTA and trichloroacetic acid followed by methanol. The combined extract was subjected to a two-track cleanup and concentration on either hydrophilic polymeric or weak cation exchange solid phase extraction cartridges. The extracts are analyzed by LC/ion trap tandem mass spectrometry. The method was validated in dry DG matrix. Absolute recoveries of the analytes ranged from 50 to 100%. Accuracy ranged from 89 to 111% based on calibration by processed standards. The limits of detection and relative standard deviation are satisfactory to support future surveillance studies. The method was subsequently tested in three different end-products of DG: distillers dry grains, distillers wet grains and distillers grains solubles. PMID- 20304406 TI - Off-line coupling of microcolumn separations to desorption mass spectrometry. AB - The presented review provides comprehensive and detailed characteristics on microcolumn separation techniques off-line coupled to mass spectrometry. Major attention is paid to the classification of junctions between the separation column and the deposition needle and to the process by which the liquid is transferred onto the target. Both contact and non-contact deposition techniques are covered. In order to emphasize the significance of the topic of off-line separations, current commercially available devices have been compared in terms of their potential utilization in analytical chemistry with a summarization of applications used over the past few years. PMID- 20304407 TI - Analysis of sucralose and other sweeteners in water and beverage samples by liquid chromatography/time-of-flight mass spectrometry. AB - A methodology for the chromatographic separation and analysis of three of the most popular artificial sweeteners (aspartame, saccharin, and sucralose) in water and beverage samples was developed using liquid chromatography/time-of-flight mass spectrometry (LC/TOF-MS). The sweeteners were extracted from water samples using solid-phase extraction (SPE) cartridges. Furthermore, several beverages were analyzed by a rapid and simple method without SPE, and the presence of the sweeteners was confirmed by accurate mass measurements below 2-ppm error. The unambiguous confirmation of the compounds was based on accurate mass measurements of the protonated molecules [M+H](+), their sodium adducts and their main fragment ions. Quantitation was carried out using matrix-matched standard calibration and linearity of response over 2 orders of magnitude was demonstrated (r>0.99). A detailed fragmentation study for sucralose was carried out by time-of flight and a characteristic spectrum fingerprint pattern was obtained for the presence of this compound in water samples. Finally, the analysis of several wastewater, surface water and groundwater samples from the US showed that sucralose can be found in the aquatic environment at concentrations up to 2.4microg/L, thus providing a good indication of wastewater input from beverage sources. PMID- 20304408 TI - A chromatochemometric approach for evaluating and selecting the perfume maceration time. AB - A chemometric treatment of the data obtained by gas chromatography (GC) with flame ionization detector (FID) has been proposed to study the maceration time involved in perfumes manufacture with the final purpose of reducing this time but preserving the organoleptic characteristics of the perfume that is being elaborated. In this sense, GC-FID chromatograms were used as a fingerprint of perfume samples subjected to different maceration times, and data were treated by linear discriminant analysis (LDA), by comparing to a set of samples known to be macerated or not, which were used as calibration objects. The GC-FID methodology combined with the treatment of data by LDA has been applied successfully to seven different perfumes. The constructed LDA models exhibited excellent Wilks' lambdas (0.013-0.118, depending on the perfume), and up to a reduction of 57% has been achieved with respect to the maceration time initially established. PMID- 20304409 TI - Investigation of internal microstructure and thermo-responsive properties of composite PNIPAM/silica microcapsules. AB - Composite microcapsules consisting of a thermo-responsive hydrogel poly-N isopropylacrylamide (PNIPAM) and coated by silica (SiO(2)) nanoparticles have been synthesized by the inverse Pickering emulsion polymerization method. The composite capsules, whose mean diameter is in the 25-86 microm range in the expanded state, were characterized by static light scattering, atomic force microscopy (AFM), scanning electron microscopy (SEM), and laser scanning confocal microscopy (LSCM). It is reported that the hydrogel surface is uniformly covered by a monolayer of silica nanoparticles and that depending on the capsule size and degree of polymer cross-linking, either hollow-core or partially-filled hydrogel core microcapsules can be created. Equilibrium thermo-responsive behavior of the composite microcapsules is investigated and it is found that after heating the particles above the lower critical solution temperature (LCST) of PNIPAM, the shrinkage ratio V/V(max) varies from 0.8 to 0.4 for a cross-linking ratio from 0.6% to 9% on a mass basis. Dynamic temperature cycling studies reveal no hysteresis in the shrinking and recovery phases, but a small measurable dependence of the asymptotic shrinkage ratio V/V(max) on the rate of temperature change exists. The composite capsules are stable under long-term storage in both dried and hydrated states and easily re-dispersible in water. PMID- 20304410 TI - Growth modification of seeded calcite using carboxylic acids: atomistic simulations. AB - Molecular dynamics simulations were used to investigate possible explanations for experimentally observed differences in the growth modification of calcite particles by two organic additives, polyacrylic acid (PAA) and polyaspartic acid (p-ASP). The more rigid backbone of p-ASP was found to inhibit the formation of stable complexes with counter-ions in solution, resulting in a higher availability of p-ASP compared to PAA for surface adsorption. Furthermore the presence of nitrogen on the p-ASP backbone yields favorable electrostatic interactions with the surface, resulting in negative adsorption energies, in an upright (brush conformation). This leads to a more rapid binding and longer residence times at calcite surfaces compared to PAA, which adsorbed in a flat (pancake) configuration with positive adsorption energies. The PAA adsorption occurring despite this positive energy difference can be attributed to the disruption of the ordered water layer seen in the simulations and hence a significant entropic contribution to the adsorption free energy. These findings help explain the stronger inhibiting effect on calcite growth observed by p-ASP compared to PAA and can be used as guidelines in the design of additives leading to even more marked growth modifying effects. PMID- 20304411 TI - Assessment of English language learners: using parent report on first language development. AB - PURPOSE: Obtaining information on both languages of English language learners for assessment can be a challenge in a multilingual context. It is often difficult or impossible to observe a child's first language directly due to the absence of resources available in every language spoken. The objectives of this study were (1) to develop a parent questionnaire on the first language development of English language learners that is not specific to a particular language/cultural group: the Alberta Language and Development Questionnaire (ALDeQ), and (2) to test how well scores on the ALDeQ differentiated between English language learners with typical development and those with language impairment. METHOD: Participants were 139 typically developing children and 29 children with language impairment, aged 69 months with 18 months of exposure to English through preschool or school, on average. The ALDeQ consists of four sections: early milestones, current first language abilities, behaviour patterns and activity preferences, and family history. ALDeQ total scores are proportions calculated across all sections. RESULTS: t-test analyses revealed robust between-group differences for ALDeQ total scores, and for each section score, with medium to very large effect sizes. Linear discriminant function analysis showed the ALDeQ total scores to be a significant and moderate discriminator between the typically developing and language impaired group, but with better specificity than sensitivity. The early milestones section scores emerged as the strongest discriminator among the four section scores. Parent responses showed that both the typically developing and language-impaired groups included children experiencing first language loss, but nevertheless, the current first language abilities section was the second strongest between-group discriminator. CONCLUSION: The ALDeQ would be useful to speech-language pathologists for obtaining information on English language learners' first language development, in particular where the first language cannot be examined directly. The information provided by the ALDeQ could be used in conjunction with other measures in order to identify children with language impairment among English language learners. The complete ALDeQ and score interpretation information are given in Appendix A. LEARNING OUTCOMES: Readers will (1) have a general understanding of how parent report could be useful for assessment in a multilingual context; (2) be aware of how first language loss in minority language children could impact assessment, and (3) have specific knowledge of a particular parent questionnaire and how it can be used to assist in identifying English language learners with language delay/impairment. PMID- 20304412 TI - The first report of disease in a basking shark (Cetorhinus maximus). AB - Few diseases have been reported in any species of shark and none in the basking shark (Cetorhinus maximus) despite the latter being the subject of targeted hunting for over two centuries. This is the first report to describe the clinical signs and gross and microscopical pathology in a diseased basking shark that was live-stranded on the east coast of Scotland. Pyogranulomatous meningoencephalitis was present together with multifocal, predominantly non-suppurative, myocarditis with myocyte necrosis, oedema and haemorrhage. Additionally, there was full thickness ulcerative and fibrinonecrotizing dermatitis with underlying granulomatous inflammation. The aetiology could not be determined, but the lesions were suggestive of an infectious process, possibly bacterial. PMID- 20304414 TI - Percutaneous coronary intervention versus coronary artery bypass grafting for stenotic lesions after Kawasaki disease. AB - OBJECTIVE: To compare the long-term efficacy of percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) for stenotic lesions after Kawasaki disease. STUDY DESIGN: Questionnaires were sent to pediatricians in Japan in hospitals with 100 or more beds. A total of 1637 questionnaires were sent, and 1347 (82%) were returned. The primary endpoints of the study were the composite of deaths from any cause and the Q-wave myocardial infarction. The secondary endpoints were the repeat-revascularization for the target vessel. RESULTS: A total of 67 patients underwent PCI and 81 patients underwent CABG. Although the rates of the primary endpoints did not differ between the groups (hazard ratio 1.35 [95% confidence interval 0.29 to 6.32], P=.7), the rate of the secondary endpoints in the PCI group was significantly higher than that in the CABG group (hazard ratio 2.23 [95% confidence interval 1.04 to 4.76], P=.04). The benefit with CABG for the secondary endpoints was notable in patients younger than 12 years old, and who had ischemic change. CONCLUSIONS: PCI after Kawasaki disease resulted in a lower efficacy in comparison to CABG because of increased repeat-revascularization procedures. PMID- 20304413 TI - Efficacy and safety of a high protein, low carbohydrate diet for weight loss in severely obese adolescents. AB - OBJECTIVE: To evaluate the efficacy and safety of a carbohydrate restricted versus a low fat diet on weight loss, metabolic markers, body composition, and cardiac function tests in severely obese adolescents. STUDY DESIGN: Subjects were randomly assigned to 1 of 2 diets: a high protein, low carbohydrate (20 g/d) diet (high protein, low carbohydrate, HPLC) or low fat (30% of calories) regimen for 13 weeks; close monitoring was maintained to evaluate safety. After the intervention, no clinical contact was made until follow-up measurements were obtained at 24 and 36 weeks from baseline. The primary outcome was change in body mass index Z-score for age and sex (BMI-Z) at 13, 24, and 36 weeks. RESULTS: Forty-six subjects (24 HPLC, 22 in low fat) initiated and 33 subjects completed the intervention; follow-up data were available on approximately half of the subjects. Significant reduction in (BMI-Z) was achieved in both groups during intervention and was significantly greater for the HPLC group (P = .03). Both groups maintained significant BMI-Z reduction at follow-up; changes were not significantly different between groups. Loss of lean body mass was not spared in the HPLC group. No serious adverse effects were observed related to metabolic profiles, cardiac function, or subjective complaints. CONCLUSIONS: The HPLC diet is a safe and effective option for medically supervised weight loss in severely obese adolescents. PMID- 20304415 TI - Physical activity and sedentary behavior among schoolchildren: a 34-country comparison. AB - OBJECTIVE: To describe and compare levels of physical activity and sedentary behavior in schoolchildren from 34 countries across 5 WHO Regions. STUDY DESIGN: The analysis included 72,845 schoolchildren from 34 countries that participated in the Global School-based Student Health Survey (GSHS) and conducted data collection between 2003 and 2007. The questionnaire included questions on overall physical activity, walking, or biking to school, and on time spent sitting. RESULTS: Very few students engaged in sufficient physical activity. Across all countries, 23.8% of boys and 15.4% of girls met recommendations, with the lowest prevalence in Philippines and Zambia (both 8.8%) and the highest in India (37.5%). The prevalence of walking or riding a bicycle to school ranged from 18.6% in United Arab Emirates to 84.8% in China. In more than half of the countries, more than one third of the students spent 3 or more hours per day on sedentary activities, excluding the hours spent sitting at school and doing homework. CONCLUSIONS: The great majority of students did not meet physical activity recommendations. Additionally, levels of sedentariness were high. These findings require immediate action, and efforts should be made worldwide to increase levels of physical activity among schoolchildren. PMID- 20304417 TI - A higher incidence of intermittent hypoxemic episodes is associated with severe retinopathy of prematurity. AB - OBJECTIVE: Retinopathy of prematurity (ROP), a vasoproliferative disorder of the retina in preterm infants, is associated with multiple factors, including oxygenation level. We explored whether the common intermittent hypoxemic events in preterm infants are associated with the development of ROP. STUDY DESIGN: Oxygen desaturation events were quantified in 79 preterm infants (gestational age, 24 to 27-6/7 weeks) during the first 8 weeks of life. Infants were classified as requiring laser treatment for ROP versus having less severe or no ROP. A linear mixed model was used to study the association between the incidence of intermittent hypoxia and laser treatment of ROP, controlling for gestational age, sex, race, multiple births, and initial severity of illness. RESULTS: For all infants, hypoxemic events increased with postnatal age (P<.001). Controlling for all covariates, a higher incidence of oxygen desaturation events was found in the infants undergoing laser therapy for ROP (P<.001), males (P<.02), and infants of younger gestational age (P<.003). CONCLUSIONS: The incidence of hypoxemic events was higher in infants with ROP requiring laser therapy. Therapeutic strategies to optimize oxygenation in preterm infants should include minimization of desaturation episodes, which may in turn decrease serious morbidity in this high-risk population. PMID- 20304418 TI - A national survey of pediatric residents and delivery room training experience. AB - OBJECTIVE: To investigate current delivery room training experience in US pediatric residency programs and the relationship between volume of delivery room training and confidence in neonatal resuscitation skills. STUDY DESIGN: Links to a web-based survey were sent to pediatric residency programs and distributed to residents. The survey concerned delivery room attendance during training and comfort level in leading neonatal resuscitation for various scenarios. Comfort level was rated on a 1 to 9 scale. Mixed models accounted for residency programs as random effects. RESULTS: For PL-3s, the mean number of deliveries attended was 60 (standard deviation, 43), ranging from 13 to 143 deliveries for individual residency programs. Residents' confidence level in leading neonatal resuscitation was higher when attending more deliveries, with 90.3% of those attending>48 deliveries having average score 5 or greater vs 51.5% of those attending<21 deliveries. Higher attendance also correlated with confidence in endotracheal intubation and umbilical line placement. CONCLUSIONS: Wide variability existed within and among residency programs in number of deliveries attended. Volume of experience correlated with confidence in leading neonatal resuscitation and related procedural skills. PMID- 20304419 TI - Research initiatives in neonatal hypoglycemia. PMID- 20304420 TI - Non-immune goiter and hypothyroidism in a 19-week fetus: a plea for conservative treatment. AB - Hypothyroidism was documented by cordocentesis at 19 weeks in a fetus with non immune goiter. Intra-amniotic thyroxine was injected at 25 weeks when amniotic fluid volume increased. Psychomotor outcome was normal. We argue that intra amniotic thyroxine should not be used to treat the hypothyroidism but only to correct the development of polyhydramnios. PMID- 20304421 TI - State-level child health system performance and the likelihood of readmission to children's hospitals. AB - OBJECTIVES: To assess the relationship between children's hospital readmission and the performance of child health systems in the states in which hospitals are located. STUDY DESIGN: We conducted a retrospective cohort study of 197,744 patients 2 to 18 years old from 39 children's hospitals located in 24 states in the United States in 2005. Subjects were observed for a year after discharge for readmission to the same hospital. The odds of readmission were modeled on the basis of patient-level characteristics and state child health system performance as ranked by the Commonwealth Fund. RESULTS: A total of 1.8% of patients were readmitted within a week, 4.8% within a month, and 16.3% within 365 days. After adjustment for patient-level characteristics, the probability of readmission varied significantly between states (P=.001), and the likelihood of readmission during the ensuing year increased as the states' health system performance ranking improved. States in the best ranking quartile had a 2.03% higher readmission rate than states in the lowest quartile (P=.02); the same directional relationship was observed for readmission intervals from 1 to 365 days after discharge. CONCLUSIONS: Hospital readmission rates are significantly related to the performance of the surrounding health care system. PMID- 20304422 TI - Is there a role for primary care physicians' screening of excessive weight and eating concerns in adolescence? AB - OBJECTIVES: To determine the extent to which adolescents with excessive weight concerns and eating concerns are in contact with primary care physicians and could thus be identified in primary care. STUDY DESIGN: A representative sample of 7548 (16 to 20 years old) students completed a self-administered questionnaire on health-related topics (2002 Swiss Multicenter Adolescent Health Survey). Adolescents with excessive weight and eating concerns were compared with control subjects for frequency of somatic complaints and primary care visits in the past year. Analyses were stratified by sex. Logistic regression was used to adjust for confounders. RESULTS: Excessive weight and eating concerns were frequent in adolescents, particularly in girls (girls, 13.9%; boys, 1.6%). Adolescents with these concerns reported more frequent somatic complaints compared with their peers. Nearly 80% of them were in contact with a primary care physician at least once a year. CONCLUSION: Primary care physicians are in contact with adolescents who have excessive weight and eating concerns. Identification of these concerns should be encouraged for appropriate management. PMID- 20304423 TI - Fatal familial lung disease caused by ABCA3 deficiency without identified ABCA3 mutations. AB - OBJECTIVE: To test the hypothesis that some functionally significant variants in the gene encoding member A3 of the ATP Binding Cassette family (ABCA3) are not detected using exon-based sequencing approaches. STUDY DESIGN: The first of 2 female siblings who died from neonatal respiratory failure was examined for mutations with sequence analysis of all ABCA3 exons and known regulatory elements within the 5' untranslated region. Lung tissue from both siblings was immunostained for ABCA3 and examined with electron microscopy. Segregation of ABCA3 alleles was determined with analysis of polymorphisms in the parents and all children. RESULTS: No mutations were identified with ABCA3 sequence analysis in the first affected infant. Affected siblings were concordant for their ABCA3 alleles, but discordant from those of their unaffected siblings. ABCA3 protein was not detectable with immunostaining in lung tissue samples from both affected infants. Electron microscopy demonstrated small, dense lamellar bodies, characteristically seen with ABCA3 mutations. CONCLUSIONS: The segregation of ABCA3 alleles, absence of ABCA3 immunostaining, lung pathology, and ultrastructural findings support genetic ABCA3 deficiency as the cause of lung disease in these 2 infants, despite the lack of an identified genetic variant. PMID- 20304424 TI - Seasonality of child homicide. AB - OBJECTIVE: To determine whether there is seasonal variation (by season and month of year) in homicides among young children. STUDY DESIGN: Homicide deaths in childrenor=1 event per hour associated with >or=3% oxygen desaturation. Subjective symptoms such as witnessed apnea, excessive daytime sleepiness, difficulty initiating and maintaining sleep, and habitual loud snoring were considered present if they occurred frequently or almost always. Body mass index percentiles were calculated with childhood growth charts from the Centers for Disease Control and Prevention adjusted for sex and age. RESULTS: The mean age at assessment was 8.5 years at baseline and 13.7 years at follow-up, respectively. Incident SDB was more common in boys (odds ratio [OR]=3.93, P=.008, confidence interval [CI]=1.41-10.90). Children with prevalent SDB were more likely to be boys (OR=2.48, P=.006) and had a greater increase in body mass index percentile change (OR 1.01, P=.034). Children with prevalent SDB also had 3.41 greater odds for development of obesity from baseline to follow-up in comparison with children with prevalent NoSDB. CONCLUSIONS: Adolescent boys are more likely to have persistent and incident SDB than girls. Children with prevalent SDB are more likely to have development of obesity. These risks are similar to those observed in adults. PMID- 20304432 TI - Lymhomatosis cerebri--a rare cause of leukoencephalopathy. AB - BACKGROUND: Lymphomatosis cerebri is a rare variant of primary central nervous system lymphoma. Clinically it presents usually as rapidly progressive dementia and is accompanied by extensive white matter changes in magnetic resonance imaging (MRI). CASE DESCRIPTION: A 49-year-old immuno-competent male who complained of dull diffuse headache, rapidly deteriorated in higher functions over a 6 month period. On examination he was globally declined in cognitive functions and had papilledema. MRI showed extensive white matter lesions. He became temporarily alert, and attentive after a course of parenteral steroids. However within three weeks he relapsed and a wedge biopsy of the brain revealed histopathology consistent with lymphomatosis cerebri. CONCLUSION: The differential diagnosis of diffuse white matter diseases is constantly expanding. In the background of a rapidly progressing subcortical dementia and extensive white matter disease, neoplastic disorders of the brain especially lymphomatosis cerebri should be considered. Early tissue diagnosis is important for specific treatment and interventions. PMID- 20304433 TI - Risk stratification of men choosing surveillance for low risk prostate cancer. AB - PURPOSE: We sought to predict biopsy progression in men on prostate cancer surveillance. MATERIALS AND METHODS: A total of 376 men with a median age of 65.5 years (range 45.8 to 79.5) with low risk prostate cancer on surveillance underwent at least 1 followup biopsy after diagnosis. Progression was defined at surveillance biopsy as Gleason pattern 4 or 5, greater than 2 biopsy cores with cancer or greater than 50% involvement of any core with cancer. Proportional hazards analysis was used to evaluate the association between covariates and progression at surveillance biopsy. The Kaplan-Meier method was used to estimate the probability of disease progression. RESULTS: Of the 376 men 123 (32.7%) had progression a median of 5.6 years (range 0.3 to 8.5) after diagnosis. Percent free PSA and maximum percent core involvement at diagnosis were associated with progression, allowing stratification of the progression risk at initial surveillance biopsy. Cancer presence and PSA density at initial surveillance biopsy were associated with subsequent progression, allowing stratification of the cumulative incidence of progression 3 years after initial surveillance biopsy (cumulative incidence 11.1%, 95% CI 4.7 to 25.2 for negative biopsy and PSAD less than 0.08 ng/ml/cm(3) vs 53.6%, 95% CI 38.6 to 70.0 for positive biopsy and PSAD 0.08 ng/ml/cm(3) or greater, log rank test p <0.0001). CONCLUSIONS: Clinical variables at diagnosis and at first surveillance biopsy during followup in an active surveillance program can be used to inform men about the likelihood of an unfavorable prostate biopsy. This information could improve patient and physician acceptance of active surveillance in carefully selected men. PMID- 20304434 TI - Re: Low annual caseloads of United States surgeons conducting radical prostatectomy. C. J. Savage and A. J. Vickers. J Urol 2009; 182: 2677-2681. PMID- 20304435 TI - Re: Female epispadias management: perineal urethrocervicoplasty versus classical Young-Dees procedure. A. Cheikhelard, Y. Aigrain, H. Lottmann and S. Lortat Jacob. J Urol, suppl, 2009; 182: 1807-1812. PMID- 20304436 TI - Stable Pb isotope ratios in aerosols, precipitation, and size-fractionated particulate matter in the Gulf of Maine, Scotian Shelf, and Labrador Sea. AB - Measurements of Pb isotopes in aerosols, precipitation, and size-fractionated particulate matter from the Gulf of Maine, Scotian Shelf and Labrador Sea are used to investigate the source of Pb. The (206)Pb/(207)Pb ratio in aerosols and precipitation collected at New Castle, NH suggests that anthropogenic Pb is a mixture of US and Canadian sources. (206)Pb/(207)Pb ratios in >53 microm particulate matter from the Gulf of Maine and Scotian Shelf slope waters are consistent with contaminant Pb inputs predominantly from US and Canadian sources, while in shelf waters (206)Pb/(207)Pb ratios in >0.4 microm and >53 microm particles are consistent with a mixture of US and Canadian sources, as well as Pb associated with resuspended surface sediment. (206)Pb/(207)Pb ratios in particulate matter (>0.4 microm, 10-53 microm, and >53 microm) from Labrador Sea surface waters range from 1.165 to 1.211 and are a mixture of Pb derived from ore compositions consistent with Broken Hill, Australia and southeast Missouri, US sources. PMID- 20304437 TI - Principal processes within the estuarine salinity gradient: a review. AB - The salinity gradient is one of the main features characteristic of any estuarine ecosystem. Within this gradient in a critical salinity range of 5-8 PSU the major biotic and abiotic processes demonstrate non-linear dynamics of change in rates and directions. In estuaries, this salinity range acts as both external ecological factor and physiological characteristics of internal environment of aquatic organisms; it divides living conditions appropriate for freshwater and marine faunas, separates invertebrate communities with different osmotic regulation types, and defines the distribution range of high taxa. In this paper, the non-linearity of biotic processes within the estuarine salinity gradient is illustrated by the data on zooplankton from the Baltic estuaries. The non-tidal Baltic Sea provides a good demonstration of the above phenomena due to gradual changes of environmental factors and relatively stable isohalines. The non linearity concept coupled with the ecosystem approach served the basis for a new definition of an estuary proposed by the authors. PMID- 20304438 TI - The influence of Spartina maritima on carbon retention capacity in salt marshes from warm-temperate estuaries. AB - Salt marshes constitute highly productive systems playing an important role on ecosystem functions. The aim of this study is to compare the role of Spartina maritima salt marshes on carbon cycling. Thus, four salt marshes located in two mesotidal estuarine systems (Tagus and Mondego, two salt marshes per estuary) were studied. The S. maritima above- and belowground biomass, carbon production, decomposition rates (through a litterbag experiment) and carbon content in the sediment were estimated for a one year period in both systems and compared. In Corroios (located at the Tagus estuary) S. maritima salt marsh had the highest belowground production (1008 gC m(-2) y(-1)), slower decomposition rate (k=0.0024 d(-1)), and the highest carbon content in sediments (750 gC m(-2) y(-1)); and thus, the highest carbon retention capacity. The other three salt marshes had comparatively higher aboveground productions, higher decomposition rates and lower carbon retention capacity. Therefore, Corroios had the most important carbon cycling characteristics. As a whole, results show that differences in carbon cycling in salt marshes depend mostly on its own characteristics and maturity, rather than the system itself. The intrinsic characteristics of the salt marshes, namely the physicochemical conditions determined by the maturity of the system, are more important factors affecting the role of warm-temperate mesotidal salt marshes as carbon sinks. PMID- 20304439 TI - The oxygen fluxes of sandy littoral areas: quantifying primary and secondary producers in the Baltic Sea. AB - The study aimed to estimate the total oxygen flow through the shallow littoral of the Gulf of Gdansk (southern Baltic Sea). Daily primary production and daily oxygen consumption by meso- and macroplankton and meio- and macrobenthos were measured, as well as the remaining (abiotic/microbial) oxygen consumption of the water column and bottom sediment. The daily gross primary production was 5.0 l of oxygen m(-2), oxygen consumption was 9.2 l m(-2), of which 16% were used by the water column and 84% by the bottom sediment. Abiotic oxygen consumption in water column contributed to less than 5% of the total oxygen consumption, and in the bottom sediment to 67%. Mesoplankton in the water column and meiobenthos in the bottom sediments were the major oxygen consumers in the littoral (67% and 26%, respectively). PMID- 20304440 TI - [Non-interventional post-authorisation studies in Spain: justification and basis of a new regulation]. PMID- 20304441 TI - [Psychoactive drugs use and related visits of adolescents to the emergency department]. AB - BACKGROUND AND OBJECTIVES: To describe psychoactive substances (PS)-related visits of adolescents to the emergency department and to explore possible differential features in patients according to the kind of PS consumed. PATIENTS AND METHODS: Observational and analytic study. PS-related visits of adolescents to the emergency department during 30 months were studied. Patients were divided in two groups: those with alcohol intoxication only (Group_1) and those with other PS (Group_2) and they were compared. RESULTS: 333 consults were included, corresponding to 321 patients. Their mean age was 16,1 years (SD:1,1 years). Two hundred sixty-two(78,7%) were alcohol-related visits, and 110(33%) were related with another PS consumption. Of the 262 alcohol-related visits, 223 were only related with alcohol(Group_1), while the other 110 visits made up Group_2. Group_2 was composed of more males, more adolescents placed in Institutional Care and more adolescents with psychiatric records than Group_1. Likewise, distribution of Group_2 visits was less predictable than distribution of Group_1. CONCLUSIONS: PS consumption is a frequent major complaint in an Emergency Department. There are more poly-intoxications in males with psycho-social problems. In those cases, consumption seems to happen regardless of the time in the day or the day of the week. PMID- 20304442 TI - Peripheral signals of energy homeostasis as possible markers of training stress in athletes: a review. AB - The importance of physical exercise in regulating energy balance and ultimately body mass is widely recognized. There have been several investigative efforts in describing the regulation of the energy homeostasis. Important in this regulatory system is the existence of several peripheral signals that communicate the status of body energy stores to the hypothalamus including leptin, adiponectin, ghrelin, interleukin-6, interleukin-1beta, and tumor necrosis factor-alpha--different cytokines and other peptides that affect energy homeostasis. In certain circumstances, all these peripheral signals may be used to reveal the condition of the athlete as the result of several months of prolonged exercise training. These hormone and cytokine concentrations characterize a physical stress condition in which different hormone and cytokine responses are apparently linked to changes in physical performance. The possibility to use these peripheral signals as markers of training stress (and possible overreaching/overtraining) in elite athletes should be considered. These measured hormone and cytokine levels could also be used to characterize the physical stress of single exercise session, as the hormone and cytokine response to exercise may actually be a response to the concurrent energy deficit. In summary, different peripheral signals of energy homeostasis may be sensitive to changes in specific training stress and may be useful for predicting the onset of possible overreaching/overtraining in athletes. PMID- 20304443 TI - Hypoglycemic and insulin-sensitizing effects of berberine in high-fat diet- and streptozotocin-induced diabetic rats. AB - Hypoglycemic effects of berberine (BBR) have been reported in several studies in cell and animal models. However, the mechanisms of action are not fully understood. The present study was therefore aimed at determining the effect and underlying mechanisms of action of BBR on diabetes in a high-fat diet- and streptozotocin-induced diabetic rat model. Ninety male Sprague-Dawley rats, 150 to 170 g, were housed individually in cages. Two groups (n = 12 each) were fed the AIN-93G diet (normal control) and the same diet modified to contain 33% fat and 2% cholesterol (high-fat control), respectively. The third group (n = 66) was fed the high-fat diet and injected intraperitoneally 2 weeks later with 35 mg/kg body weight of streptozotocin in citrate buffer (pH 4.5). The rats in both control groups were injected with the vehicle. After 12 days, rats with semifasting (5 hours) blood glucose levels between 14 and 25 mmol/L were divided into 4 groups (n = 12 each) and treated with 0 (diabetic control), 50, 100, and 150 mg/kg/d of BBR for 6 weeks while continuing on the high-fat diet. Hypoglycemic effects of BBR were consistently demonstrated by semifasting and fasting blood glucose levels, and insulin-sensitizing effects were seen during oral glucose tolerance testing. Berberine also reduced food intake while having no effect on body weight in diabetic rats. No effect of BBR was observed on plasma levels of insulin, adipokines (leptin and adiponectin), or inflammatory cytokines (tumor necrosis factor-alpha and C-reactive protein). Berberine did not affect the state of oxidative stress as assessed by the activity of superoxide dismutase and the concentrations of malondialdehyde and reduced and oxidized glutathione in the liver. These findings demonstrated the hypoglycemic and insulin-sensitizing capabilities of BBR, with the underlying mechanisms awaiting further investigation. PMID- 20304444 TI - [Orbital tumors arising from paranasal sinuses]. AB - Orbital tumors arising from paranasal sinuses comprise mucoceles and malignant ethmoidal tumors. Most often, anamnestic, clinical, and radiological data as well as endoscopic biopsy performed by an ENT surgeon provide the preoperative diagnosis. If the tumor is benign, surgery can cure the patient. It is associated with chemotherapy and radiotherapy if the tumor is malignant. PMID- 20304445 TI - [History of orbital surgery]. PMID- 20304446 TI - [Orbital metastasis]. AB - Orbital metastases are uncommon, accounting for 4% of all adult orbital tumors. The mean age at time of presentation is 60 years. The primary tumor is most often a carcinoma involving the breast (40%), lung (11%), or prostate (8%). Proptosis is the main clinical sign at diagnosis and is often associated with visual impairment, pain or ptosis. Imaging features are not specific; nevertheless, an enhanced extraconal tumor with osteolysis suggests the diagnosis. From a pathological point of view, there are no differences between the metastasis and the primary tumor. Regarding the average survival, the gold standard treatment remains radiotherapy. PMID- 20304447 TI - Quiet heroes after the quake. PMID- 20304448 TI - [Functional imaging of tumors. Part 2]. AB - Most advances in conventional diagnostic imaging techniques have focused on improving the spatial resolution and speed of acquisition of images or on new contrast agents. However, tumors are extremely complex biological models with a series of characteristics like hypoxia, metabolism, cellularity, angiogenesis, and functionality of the lymph nodes that are very important in oncology but cannot be adequately studied with these diagnostic imaging methods. In this article, we discuss the possible contributions of different functional imaging techniques based on computed tomography, magnetic resonance imaging, or positron emission tomography to obtain information about different biological processes and characteristics that are very important for diagnosing, staging, planning treatment, evaluating the response to treatment, and monitoring the evolution of cancer patients, as well as for the development of new drugs. PMID- 20304449 TI - [Aneurysmatic bone cyst coexisting with osteosarcoma. Radiopathologic discussion]. AB - Aneurysmatic bone cysts are benign lesions of unknown origin. It has been postulated that they might occur in reaction to trauma or to a primary benign (giant cell tumor, chondroblastoma, etc.) or malignant (osteosarcoma) bone tumor that results in local hemodynamic changes. Their malignant transformation is controversial. We present a case of low grade osteosarcoma with a radiologic progression that was indistinguishable from that of an aneurysmatic bone cyst. PMID- 20304450 TI - Molecular and virological studies on contagious pustular dermatitis isolates from Egyptian sheep and goats. AB - Orf virus was clinically diagnosed from different field cases of sheep and goat in Hawamdia, Giza, Egypt during the summer 2006. Skin scabs were collected and used for virus isolation, electron microscopy, PCR and sequencing for confirmation, and differential diagnosis. The aetiological virus was fruitfully isolated on the chorio-allantoic membrane of SPF embryonated chicken eggs indicated by expressing the characteristic pock lesions of Poxviridae family. Electron microscopy examination exposed negatively stained oval-shape virus particles trait for members of the genus Parapoxvirus. A 392 bp fragment of the late transcription factor (VLTF-1) gene of orf virus was amplified by PCR from the DNA extracted from the isolates. Phylogenetic analysis revealed 99% identity with other orf virus strains reported worldwide. Selection and processing of clinical specimens and PCR assay applied in this endeavor, presented a reliable laboratory diagnostic tool for orf infections and first molecular characterization of Egyptian orf isolates. PMID- 20304451 TI - First report on Parafilaria bovicola (Nematoda: Filaroidea) in Germany. AB - From September 2008 to April 2009 several cases of spontaneous bleeding and nodules from the back and withers area of cattle otherwise considered as healthy have been reported from several farms in south-western and southern Germany. Successive investigation of these cases gave strong evidence of Parafilaria (P.) bovicola infections due to their seasonal occurrence and specific pathological lesions. There was no history of animal import from endemic countries for the affected cattle herds. In one case, a nodule containing nematode fragments and an intact female nematode were recovered from a slaughtered White Galloway bull. This sample was identified as P. bovicola and is the first report of bovine parafilariosis in Germany. PMID- 20304452 TI - Incisional ventral hernias: review of the literature and recommendations regarding the grading and technique of repair. AB - Despite advances in surgical technique and prosthetic technologies, the risks for recurrence and infection are high following the repair of incisional ventral hernias. High-quality data suggest that all ventral hernia repairs should be reinforced with prosthetic repair materials. The current standard for reinforced hernia repair is synthetic mesh, which can reduce the risk for recurrence in many patients. However, permanent synthetic mesh can pose a serious clinical problem in the setting of infection. Assessing patients' risk for wound infection and other surgical-site occurrences, therefore, is an outstanding need. To our knowledge, there currently exists no consensus in the literature regarding the accurate assessment of risk of surgical-site occurrences in association with or the appropriate techniques for the repair of incisional ventral hernias. This article proposes a novel hernia grading system based on risk factor characteristics of the patient and the wound. Using this system, surgeons may better assess each patient's risk for surgical-site occurrences and thereby select the appropriate surgical technique, repair material, and overall clinical approach for the patient. A generalized approach and technical considerations for the repair of incisional ventral hernias are outlined, including the appropriate use of component separation and the growing role of biologic repair materials. PMID- 20304453 TI - Evaluation of a pediatric protocol of intrapleural urokinase for pleural empyema: a prospective study. AB - BACKGROUND: Intrapleural urokinase has been shown to be effective in the treatment of pleural effusions in children. However, optimal dosing in children is debated. The aim of this study was to prospectively evaluate a specific pediatric protocol of intrapleural urokinase. METHODS: All children admitted to a single institution over a 6-year period with a diagnosis of pleural empyema were managed with chest tube and fibrinolytics. Clinical data were collected prospectively. Urokinase (56,000 IU in 56 mL saline/m(2) body surface) was administered twice daily, and was continued until resolution of the effusion. Further operative treatment was considered if urokinase treatment was unsuccessful after >/=3 days. Results are shown as median values (interquartile range). RESULTS: Forty-one consecutive children aged 4.4 (3.2-6.9) years were included in the study, and received 420,000 (280,000-750,000) IU of urokinase over 7 (4-8) days. Suction through the chest drain was applied for 8 (6-10) days, and IV antibiotics were discontinued after 12 (10-15) days from the start of intrapleural fibrinolytics. Four children (9.8%) required 5 additional operative procedures (3 thoracoscopic debridements and 2 minithoracotomic debridements). Patients were discharged after 13 (11-16) days from the beginning of intrapleural urokinase. No major side effects attributable to urokinase were observed. CONCLUSION: Intrapleural instillation of urokinase according to a specific pediatric protocol results in a high success rate when applied as a primary treatment in children with pleural empyema. Administration of a size-adjusted dose of urokinase proved to be safe and could optimize drug utilization. PMID- 20304454 TI - Single administration of di(n-butyl) phthalate delays spermatogenesis in prepubertal rats. AB - Morphological alterations in seminiferous tubules caused by single administration of di(n-butyl) phthalate (DBP) in 3-week-old rats were investigated throughout the first wave of spermatogenesis. Single administration of DBP (500 mg/kg) showed progressive detachment and displacement of spermatogenic cells and disappearance of tubular lumen at 3h after treatment, and then showed thin seminiferous epithelia and wide tubular lumen at day 1 (D1). At D1, quite significant numbers of apoptotic spermatogenic cells were detected, and then they gradually decreased in accordance with the passage of time. In contrast, the testes revealed lower weight gain, even after completion of first wave of spermatogenesis in the DBP-treated group, compared to the control. In order to clarify whether spermatogenic cells differentiate into mature spermatids in the DBP-treated rats, immunohistochemical staining for Hsc 70t, a specific marker for elongate spermatids, was carried out. As a result, the decrease in mature spermatids in the DBP-treated testes, compared to the control, was demonstrated. For example, at D20 (41-day-old) after treatment, the most advanced spermatids in the tubules from rats in the DBP-treated groups were steps 2-4, while those of the control were steps 12-13. Moreover, in some tubules, pachytene spermatocytes were the most advanced spermatogenic cell. At D30 (51-day-old) after treatment, maturation of spermatogenic cells in the DBP-treated rats proceeded further, and the most advanced spermatids in tubules were steps 8-9, while those of the control were steps 15-19. These results lead us to the postulation that a single administration of DBP to prepubertal rats delays maturation of spermatogenic cells, even after completion of first wave of spermatogenesis. PMID- 20304455 TI - Complete genomic sequence and an infectious BAC clone of feline herpesvirus-1 (FHV-1). AB - Infection with feline herpesvirus-1 (FHV-1) is a major cause of upper respiratory and ocular diseases in Felidae. We report the first complete genomic sequence of FHV-1, as well as the construction and characterization of a bacterial artificial chromosome (BAC) clone of FHV-1, which contains the entire FHV-1 genome and has the BAC vector inserted at the left end of U(L). Complete genomic sequences were derived from both the FHV-1 BAC clone and purified virion DNA. The FHV-1 genome is 135,797bp in size with an overall G+C content of 45%. A total of 78 open reading frames were predicted, encoding 74 distinct proteins. The gene arrangement is collinear with that of most sequenced varicelloviruses. The virus regenerated from the BAC was very similar to the parental C-27 strain in vitro in terms of plaque morphology and growth characteristics and highly virulent in cats in a preliminary in vivo study. PMID- 20304456 TI - Antibody-mediated neutralization of Ebola virus can occur by two distinct mechanisms. AB - Human Ebola virus causes severe hemorrhagic fever disease with high mortality and there is no vaccine or treatment. Antibodies in survivors occur early, are sustained, and can delay infection when transferred into nonhuman primates. Monoclonal antibodies (mAbs) from survivors exhibit potent neutralizing activity in vitro and are protective in rodents. To better understand targets and mechanisms of neutralization, we investigated a panel of mAbs shown previously to react with the envelope glycoprotein (GP). While one non-neutralizing mAb recognized a GP epitope in the nonessential mucin-like domain, the rest were specific for GP1, were neutralizing, and could be further distinguished by reactivity with secreted GP. We show that survivor antibodies, human KZ52 and monkey JP3K11, were specific for conformation-dependent epitopes comprising residues in GP1 and GP2 and that neutralization occurred by two distinct mechanisms; KZ52 inhibited cathepsin cleavage of GP whereas JP3K11 recognized the cleaved, fusion-active form of GP. PMID- 20304458 TI - Electro-oxidation of reverse osmosis concentrates generated in tertiary water treatment. AB - This work investigates the application of the electro-oxidation technology provided with boron doped diamond (BDD), an electrode material which has shown outstanding properties in oxidation of organic and inorganic compounds, for the treatment of reverse osmosis (RO) concentrates generated in tertiary wastewater treatment plants (WWTP). Chemical oxygen demand (COD), ammonium and several anions were measured during the electro-oxidation process, and the influence of the applied current density (20-200A/m(2)) was analysed on process kinetics. Analytical assessment showed that several emerging pollutants (pharmaceuticals, personal care products, stimulants, etc.) were presented both in the effluent of the secondary WWTP as well as in the RO concentrate. For this reason, a group of 10 emerging pollutants, those found with higher concentrations, was selected in order to test whether electro-oxidation can be also applied for their mitigation. In the removal of emerging pollutants the electrical current density in the range 20-100A/m(2) did not show influence likely due to the mass transfer resistance developed in the process when the oxidized solutes are present in such low concentrations. Their removal rates were fitted to first order expressions, and the apparent kinetic constants for the anodic oxidation of each compound were calculated. Finally, the formation of trihalomethanes (THMs) has been checked; concluding that after selecting the appropriate operational conditions the attained concentration is lower than the standards for drinking water established in European and EPA regulations. PMID- 20304457 TI - Lack of complex N-glycans on HIV-1 envelope glycoproteins preserves protein conformation and entry function. AB - The HIV-1 envelope glycoprotein complex (Env) is the focus of vaccine development aimed at eliciting humoral immunity. Env's extensive and heterogeneous N-linked glycosylation affects folding, binding to lectin receptors, antigenicity and immunogenicity. We characterized recombinant Env proteins and virus particles produced in mammalian cells that lack N-acetylglucosaminyltransferase I (GnTI), an enzyme necessary for the conversion of oligomannose N-glycans to complex N glycans. Carbohydrate analyses revealed that trimeric Env produced in GnTI(-/-) cells contained exclusively oligomannose N-glycans, with incompletely trimmed oligomannose glycans predominating. The folding and conformation of Env proteins was little affected by the manipulation of the glycosylation. Viruses produced in GnTI(-/-) cells were infectious, indicating that the conversion to complex glycans is not necessary for Env entry function, although virus binding to the C type lectin DC-SIGN was enhanced. Manipulating Env's N-glycosylation may be useful for structural and functional studies and for vaccine design. PMID- 20304459 TI - Molecular effects of endocrine-disrupting chemicals on the Chironomus riparius estrogen-related receptor gene. AB - Endocrine-disrupting chemicals (EDCs) mimic the action of endogenous estrogen hormones; consequently, they can interfere with the endocrine systems of a variety of organisms. There is global concern regarding the potential impacts of EDCs on the aquatic environment. To evaluate the effects of EDCs on the estrogen related receptors (ERR) of Chironomus, we characterized full-length cDNA sequences of the ERR gene from Chironomus riparius. The complete cDNA sequence of the ERR gene was found to be 1332bp in length. The results of our phylogenetic analysis demonstrated that C. riparius ERR was most closely related to that of mosquitoes. The basal level of ERR mRNA was expressed abundantly during different life-history stages, with the exception of adult males. Additionally, ERR gene expression was upregulated significantly in C. riparius exposed to bisphenol A (BPA) and 4-nonylphenol (NP) at all concentrations assayed after 24h of exposure. The ERR gene was significantly upregulated following short periods of exposure to di(2-ethylhexyl)phthalate (DEHP) concentrations of only 50mgL(-1). However, under long-term exposure conditions, ERR expression was induced to a significant degree after BPA, NP, and DEHP exposure at all concentrations assayed. Furthermore, the luciferase reporter gene assay revealed increased ERR expression following exposure to these compounds. Collectively, these findings indicate that EDCs influence the expression of ERR in Chironomus species. PMID- 20304460 TI - Indoor measurements of the sum of the nitrate radical, NO3, and nitrogen pentoxide, N2O5 in Denmark. AB - There is a need for indoor measurements of nitrate radicals (NO(3)) and nitrogen pentoxide (N(2)O(5)) to better understand removal and transformation of volatile organic compounds in indoor environments, and to evaluate the possible health effects from exposure to nitrated reaction products. NO(3) and NO(2) react to form N(2)O(5) in the presence of a third molecule, and the fast equilibrium necessitates measurements of both NO(3) and N(2)O(5) in the evaluation of indoor NO(3) chemistry. The sum of these two species, NO(3)( *), was quantified in an office building in Denmark by measuring an oxidation product of the cyclohexene/NO(3) reaction in a flow-tube set-up. NO(3)( *) concentrations ranged from 1 to 58ppt, where N(2)O(5) was estimated to account for more than 68%. The concentrations of the precursors, NO(2) and O(3), and the photolysis of NO(3) were parameters, which clearly influenced NO(3)( *) apparent from the different precursor concentrations, lighting and daylight versus dark samples in this study. Also indoor air pollutants, in particular alkenes such as limonene and alpha-pinene, can significantly reduce NO(3)( *). These first indoor measurements of NO(3)( *), warrant further high time resolution measurements of NO(3), N(2)O(5), and organic nitrates indoors. PMID- 20304461 TI - The effects of alkaline dosage and Si/Al ratio on the immobilization of heavy metals in municipal solid waste incineration fly ash-based geopolymer. AB - The present research explored the application of geopolymerization for the immobilization and solidification of municipal solid waste incineration (MSWI) fly ash. The influence of alkaline activator dosage and Si/Al molar ratio on the compressive strength and microstructure of MSWI fly ash-based geopolymer was investigated. A geopolymer with the highest strength was identified to occur at an intermediate alkaline activator dosage and Si/Al ratio, and the optimal Na/MSWI fly ash and Si/Al molar ratio was close to 2.8 mol kg(-1) and 2.0, respectively. IR spectra showed that higher alkaline activator dosage enhanced the structural disruption of the original aluminosilicate phases and a higher degree of polymerization of the geopolymer networks. At low Si/Al ratio, there was an increasing number of tetrahedral Al incorporating into the silicate backbone. As the Na/MSWI fly ash ratio increased, the microstructure changed from containing large macropores to more mesopores and micropores, indicating that more geopolymers are formed. Furthermore, the pore volume distribution of geopolymers was observed to shift to larger pores as the Si/Al ratio increased, which suggests that the soluble silicon content serves to reduce the amount of geopolymers. Heavy metal leaching was successfully elucidated using the first order reaction/reaction-diffusion model. Combining the results from the microstructure of samples with the kinetic analysis, the immobilization mechanism of Cr, Cu, and Zn was inferred in this study. The methodologies described could provide a powerful set of tools for the systematic evaluation of element release from geopolymers. PMID- 20304462 TI - Comparison of dynamic mobilization of Co, Cd and Pb in sediments using DGT and metal mobility assessed by sequential extraction. AB - Management of metal-contaminated sediments requires an accurate knowledge of metal distribution and metal exchanges between the solid and solution phase. The DGT technique (diffusive gradients in thin films) provides information about the characteristics of metal release from the particles to the porewaters. However, the species of metals that participate in the exchange are not well documented. The aim of this paper was to explore the DGT response of Co, Cd and Pb, to a range of reservoir sediments exhibiting gradients of physico-chemical parameters. We also characterized the chemical partitioning of the three metals by sequential extraction to determine the nature of the sediment-bound metals species that could participate to the metal resupply to the porewaters. Results from DGT experiments and sequential extraction show that specific geochemical phases are key factors for the mobilization of individual metals towards DGT: dissolved organic matter and manganese oxides for Co, acid-volatile sulfides for Cd and particulate organic matter for Pb. Moreover, the masses of metals trapped in DGT are mainly correlated with the concentrations of metals that are easily exchangeable, specifically sorbed or weakly bound to labile organic matter. PMID- 20304463 TI - Archaeological horizons and fluvial processes at the Lower Paleolithic open-air site of Revadim (Israel). AB - In this paper we present new data pertaining to the paleo-landscape characteristics at the Acheulian site of Revadim, on the southern coastal plain of Israel. Sedimentological, isotopic, granulometric and micromorphological studies showed that the archaeological remains accumulated in an active fluvial environment where channel action, overbank flooding and episodic inundation occurred. Measurements of total organic matter and its carbon isotopic composition indicate that the hominin activity at the site started at a period of relatively drier conditions, which coincided with erosion of the preceding soil sequence. This process led to the formation of a gently-undulating topography, as reconstructed by a GIS model. Later deposition documents relatively wetter conditions, as indicated by carbon isotopic composition. Formation processes identified at the site include fluvial processes, inundation episodes that resulted in anaerobic conditions and formation of oxide nodules, as well as small scale bioturbation and later infiltration of carbonate-rich solutions that resulted in the formation of calcite nodules and crusts. The combination of micro habitats created favorable conditions that repeatedly drew hominins to the area, as seen by a series of super-imposed archaeological horizons. This study shows that site-specific paleo-landscape reconstructions should play an important role in understanding regional variation among hominin occupations and in extrapolating long-term behavioral patterns during the Middle Pleistocene. PMID- 20304464 TI - Studying post depositional damage on Acheulian bifaces using 3-D scanning. AB - In this study, we explore post-depositional damage observed on Acheulian bifacial tools by comparing two assemblages: a collection of archaeological handaxes which shows pronounced damage marks associated with high energy water accumulation system, and an experimental assemblage that was rolled and battered in a controlled simulation experiment. Scanning the two assemblages with a precise 3-D optical scanner and subjecting the measured surfaces to the same mathematical analysis enabled the development of quantitative measures assessing and comparing the degree of damage observed on archaeological and experimental tools. The method presented here enables the definition of morphological patterns typically resulting from battering and different from intentional controlled knapping. The most important kinds of damage included the formation of deep, random 'notch like' scars on the lateral edges and substantial degrees of damage to the tip of the tools, but minimal damage to the artifact's butt. Quantifying the degree of damage and its location and morphological characters allows us to present a method by which post depositional damage on archaeological tools can be measured. PMID- 20304465 TI - Integrating water and agricultural management under climate change. PMID- 20304466 TI - Aerosol chemical composition over Istanbul. AB - This study examines the chemical composition of aerosols over the Greater Istanbul Area. To achieve this 325 (PM(10)) aerosol samples were collected over Bosphorus from November 2007 to June 2009 and were analysed for the main ions, trace metals, water-soluble organic carbon (WSOC), organic (OC) and elemental carbon (EC). PM(10) levels were found to be in good agreement with those measured by the Istanbul Municipality air quality network, indicating that the sampling site is representative of the Greater Istanbul Area. The main ions measured in the PM(10) samples were Na(+), Ca(2+) and non-sea-salt sulphates (nss-SO(4)(2-)). On average, 31% of Ca(2+) was found to be associated with carbonates. Trace elements related to human activities (as Pb, V, Cd and Ni) obtained peak values during winter due to domestic heating, whereas natural origin elements like Al, Fe and Mn peaked during the spring period due to dust transport from Northern Africa. Organic carbon was found to be mostly primary and elemental carbon was strongly linked to fuel oil combustion and traffic. Both OC and EC concentrations increased during winter due to domestic heating, while the higher WSOC to OC ratio during summer can be mostly attributed to the presence of secondary, oxidised and more soluble organics. Factor analysis identified six components/sources for aerosol species in PM(10), namely traffic/industrial, crustal, sea-salt, fuel-oil combustion, secondary and ammonium sulfate. PMID- 20304467 TI - A novel mutation (g2172-->c) in the factor V gene in a Chinese family with hereditary activated protein C resistance. AB - BACKGROUND: Activated protein C resistance (APC-R) was a major risk factor for venous thromboembolism(VTE) in Caucasians, and at least 90% of APC-R were associated with the point mutation of factor V (FV) gene (Arg506-->Gln, FV Leiden). However, this genetic defect was extremely rare in Asian population. OBJECTIVE: To identify the genetic defect of FV in a Chinese family with APC-R associated with VTE. METHODS: We describe a Chinese family with a history of venous thrombosis. Blood samples were obtained from five family members (including the proband) for screening APC-R by coagulation assay and the genetic defect of FV using direct sequencing. RESULTS: Four out of five members had APC R. We identified a novel mutation (G2172-->C) in exon 13 of the FV gene, which was present in all the individuals with APC-R but was absent in the individual without APC-R. This mutation is predicted to result in the replacement of glutamate by aspartate at position 666, close to one of the APC cleavage sites. CONCLUSIONS: We have identified, for the first time, a novel mutation (G2172-->C) of FV that was associated with APC-R in a Chinese family with VTE. We speculate that this mutation interferes with cleavage at Arg679 by APC. The incomplete penetrance of thrombotic phenotype in this family, similar to that conferred by FV Leiden, suggests that it might be a weak risk factor for VTE. PMID- 20304468 TI - Serum tetranectin as a preoperative indicator for postoperative complications in Danish ovarian cancer patients. AB - OBJECTIVE: The association between tetranectin (TN) and selected lifestyle factors (smoking and alcohol) and the postoperative complication rate for ovarian cancer (OC) patients undergoing primary cytoreductive surgery has not yet been characterized. The aim of the study was to examine the value of TN, smoking and alcohol as indicators of postoperative complications in OC patients. METHODS: Serum TN was measured for 374 OC patients undergoing primary cytoreductive surgery. In addition, they reported their smoking and alcohol status. The prognostic value of variables was found with univariate and multivariate analyses using logistic regression analysis. RESULTS: In univariate analysis TN was the only one out of 8 variables that significantly predicted postoperative complications (OR=0.55 (95% CI: 0.34-0.87), P=0.01). High preoperative serum TN was associated with a low risk of postoperative complications. Stepwise reduction of the multivariate model demonstrated that TN and histology were the only significant co-variables (TN, OR=0.51 (95% CI: 0.32-0.83), P=0.006; histology, OR=1.70 (95% CI: 1.02-2.82), P=0.041). TN was the only indicator, which was statistical significant in both univariate and multivariate analyses. CONCLUSION: Preoperative serum TN is a significant indicator of postoperative complications in Danish OC patients and deserves to be validated in larger future studies. PMID- 20304469 TI - Profile of eicosanoid generation in aspirin-intolerant asthma and anaphylaxis assessed by new biomarkers. AB - BACKGROUND: It has recently demonstrated that a free radical-mediated pathway generates prostaglandins (PGs) and the corresponding prostaglandin enantiomers (ent-PGs). Aspirin-intolerant asthma and anaphylaxis accompany PGD(2) overproduction, possibly associated with mast cell activation via the COX pathway. However, free radical-mediated PG generation in the pathophysiology of these diseases, which can be demonstrated by measuring urinary ent-PGF(2)alpha, has not been reported. OBJECTIVES: To evaluate the characteristic profile of eicosanoid generation via the COX and/or free radical-mediated pathway underlying aspirin-intolerant asthma and anaphylaxis. METHODS: A comparative group analysis consisted of asthma (n = 17) and anaphylaxis (n = 8, none with aspirin-induced anaphylaxis) cases. Urinary eicosanoid concentrations were quantified as follows: 2,3-dinor-9alpha,11beta-PGF(2) by gas chromatography-mass spectrometry; leukotriene E(4), 9alpha,11beta-PGF(2), and PGs by enzyme immunoassay. RESULTS: 2,3-Dinor-9alpha,11beta-PGF(2) is a more predominant PGD(2) metabolite in urine than 9alpha,11beta-PGF(2). At baseline, the aspirin-intolerant asthma group (n = 10) had significantly higher leukotriene E(4) and lower PGE(2) concentrations in urine than the aspirin-tolerant asthma group. During the reaction, the urinary concentrations of leukotriene E(4) and PGD(2) metabolites correlatively increased, but with markedly different patterns of the mediator release, in the aspirin-intolerant asthma group and the anaphylaxis group, respectively. The urinary PGD(2) metabolites and primary PGs were significantly decreased in the aspirin-tolerant asthma group. Urinary ent-PGF(2)alpha concentrations were significantly increased in the anaphylaxis group but not the aspirin-intolerant asthma group. CONCLUSIONS: When assessed by urinary 2,3-dinor-9alpha,11beta PGF(2), PGD(2) overproduction during aspirin-intolerant bronchoconstriction was clearly identified, regardless of COX inhibition. It is evident that free radical mediated PG generation is involved in the pathophysiology of anaphylaxis. PMID- 20304470 TI - A novel method for assessing unchallenged levels of mediators in nasal epithelial lining fluid. PMID- 20304471 TI - Anti-IgE therapy results in decreased myeloid dendritic cells in asthmatic airways. PMID- 20304472 TI - Is the detection of IgE to multiple Bet v 1-homologous food allergens by means of allergen microarray clinically useful? PMID- 20304473 TI - Regulatory B cells prevent and reverse allergic airway inflammation via FoxP3 positive T regulatory cells in a murine model. AB - BACKGROUND: Parasitic helminth infections of humans have been shown to suppress the immune response to allergens. Experimentally, infection of mice with the helminth Schistosoma mansoni prevents allergic airway inflammation and anaphylaxis via IL-10 and B cells. OBJECTIVE: To identify and characterize the specific helminth-induced regulatory B-cell subpopulation and determine the mechanism by which these regulatory B cells suppress allergic airway inflammation. METHODS: IL-10-producing B cells from the spleens of helminth infected mice were phenotyped, isolated, and transferred to ovalbumin-sensitized mice, and their ability to modulate allergic airway inflammation was analyzed. RESULTS: S mansoni infection induced IL-10-producing CD1d(high) regulatory B cells that could prevent ovalbumin-induced allergic airway inflammation following passive transfer to ovalbumin-sensitized recipients. The capacity of regulatory B cells to suppress allergic airway inflammation was dependent on the expression of CD1d, and they functioned via an IL-10-mediated mechanism. Regulatory B cells induced pulmonary infiltration of CD4(+)CD25(+) forkhead box protein 3(+) regulatory T cells, independent of TGF-beta, thereby suppressing allergic airway inflammation. Regulatory B cells that were generated ex vivo also suppressed the development of allergic airway inflammation. Furthermore, the transfer of regulatory B cells reversed established airway inflammation in ovalbumin sensitized mice. CONCLUSION: We have generated in vivo and ex vivo a regulatory B cell that can prevent or reverse allergen-induced airway inflammation via regulatory T cells. PMID- 20304474 TI - Utility of peanut-specific IgE levels in predicting the outcome of double-blind, placebo-controlled food challenges. PMID- 20304475 TI - Natural killer T cells are not the predominant T cell in asthma and likely modulate, not cause, asthma. AB - Asthma is a multifactorial disease of the airways characterized by airway inflammation, mucus hypersecretion, and airway hyperresponsiveness. Conventional MHC class II-restricted CD4(+) T cells are considered a key cell in asthma pathogenesis because they have a broad T-cell receptor repertoire, providing specificity and reactivity to diverse protein allergens. This notion was challenged when a study found that invariant Natural Killer (NK) T cells were the predominant T cells in the lung and bronchoalveolar lavage fluid of all asthmatic subjects studied. This finding was provocative because invariant NKT cells have a very limited T-cell receptor repertoire and are specific for a restricted set of lipid antigens that bind to CD1d, a nonpolymorphic MHC-like molecule. However, multiple subsequent studies failed to replicate the initial study and instead found that invariant NKT cells are present as a small fraction of the total T cells in the asthmatic lung. Thus, we believe that although CD1d-restricted NKT cells might play a role in modulating the asthmatic phenotype, they are not the critical drivers of the asthmatic response, a role we believe is still held by conventional MHC class II-restricted CD4(+) T cells. PMID- 20304476 TI - Do early-life viral infections cause asthma? AB - Epidemiologic associations between viral lower respiratory infections (LRIs) and asthma in later childhood are well known. However, the question of whether such infections cause asthma or unmask asthma in a susceptible host has still not been settled. Most early evidence centered on the role of the respiratory syncytial virus; however, recent studies highlight a potential role for human rhinovirus as a risk factor for asthma. The links between early-life viral LRI and subsequent asthma are generally via wheeze; however, the presence of wheeze does not give any information about why the child is wheezing. Wheeze in early life is, at best, a fuzzy phenotype and not specific for subsequent asthma. The risk of asthma after viral LRI is increased in the presence of allergic sensitization in early life and if the infection is more severe. Atopy-associated mechanisms also appear to be involved in viral-induced acute exacerbations of asthma, especially in prolonging symptomatology after the virus has been cleared from the lungs. Breaking the nexus between viral respiratory infections and asthma may be possible with interventions designed to inhibit atopy-related effectors mechanisms from participating in the host response to respiratory viral infections. PMID- 20304477 TI - The effect of semantic relatedness on syntactic analysis: An fMRI study. AB - The sentences we process in normal conversation tend to refer to information that we are familiar with rather than abstract, unrelated information. This allows for the use of knowledge stores to help facilitate comprehension processes. In many sentence comprehension studies, the stimuli are designed such that the use of world knowledge is limited. Here, we investigated how the semantic relatedness of sentence constituents influences sentence processing. A three factor design was employed in which processing phase (sentence vs. probe), syntactic complexity (object-relative vs. conjoined active) and the semantic relatedness of the nouns within the sentence was examined. We found a differential effect in two sub regions of the left inferior frontal gyrus (LIFG). BA 44 revealed an effect of syntactic complexity while inferior portions of the LIFG (BA 47) revealed an effect of relatedness as well as an interaction between complexity and relatedness during the probe phase. In addition, significant differences in activation were observed when comparing the sentence processing and probe phases with the sentence phase eliciting stronger semantic related activation while the probe phase elicited stronger working memory related activation. PMID- 20304478 TI - Material properties and fractography of an indirect dental resin composite. AB - OBJECTIVES: Determination of material and fractographic properties of a dental indirect resin composite material. METHODS: A resin composite (Paradigm, 3M-ESPE, MN) was characterized by strength, static elastic modulus, Knoop hardness, fracture toughness and edge toughness. Fractographic analyses of the broken bar surfaces was accomplished with a combination of optical and SEM techniques, and included determination of the type and size of the failure origins, and fracture mirror and branching constants. RESULTS: The flexure test mean strength+/ standard deviation was 145+/-17 MPa, and edge toughness, T(e), was 172+/-12N/mm. Knoop hardness was load dependent, with a plateau at 0.99+/-0.02 GPa. Mirrors in the bar specimens were measured with difficulty, resulting in a mirror constant of approximately 2.6 MPa m(1/2). Fracture in the bar specimens initiated at equiaxed material flaws that had different filler concentrations that sometimes were accompanied by partial microcracks. Using the measured flaw sizes, which ranged from 35 to 100 microm in size, and using estimates of the stress intensity shape factors, fracture toughness was estimated to be 1.1+/-0.2 MPa m(1/2). SIGNIFICANCE: Coupling the flexure tests with fractographic examination enabled identification of the intrinsic strength limiting flaws. The same techniques could be useful in determining if clinical restorations of similar materials fail from the same causes. The existence of a strong load-dependence of the Knoop hardness of the resin composite is not generally mentioned in the literature, and is important for material comparisons and wear evaluation studies. Finally, the edge toughness test was found promising as a quantitative measure of resistance to edge chipping, an important failure mode in this class of materials. PMID- 20304479 TI - Effect of a new desensitizing material on human dentin permeability. AB - OBJECTIVES: Resin-modified glass ionomers (RMGI) have demonstrated clinical success providing immediate and long-term relief from root sensitivity. RMGIs have been recently introduced as paste-liquid systems for convenience of clinical usage. The objective of this study was to measure the ability of a new paste liquid RMGI to reduce fluid flow through human dentin, compared to an established single-bottle nanofilled total etch resin adhesive indicated for root desensitization. METHODS: Dentin permeability was measured on human crown sections on etched dentin, presenting a model for the exposed tubules typical of root sensitivity, and permitting measurement of the maximum permeability. In the first two groups, the etched dentin was coated with either the RMGI or adhesive, and permeability measured on the coated dentin. In a third group, a smear layer was created on the dentin with sandpaper, then the specimens were coated with the RMGI; permeability was measured on the smeared and coated dentin. Specimens from each group were sectioned and examined via scanning electron microscopy (SEM). RESULTS: Both the resin adhesive and the new paste-liquid RMGI protective material significantly reduced fluid flow through dentin, and exhibited excellent seal on dentin with either open tubules or smear-layer occluded tubules. The RMGI infiltrated the smear layer with resin during placement, penetrated dentin tubules, and formed resin tags. SIGNIFICANCE: The RMGI was equivalent to the adhesive in its ability to reduce fluid flow and seal dentin. It is therefore concluded that the new RMGI and the adhesive show the potential to offer excellent sensitivity relief on exposed root dentin. PMID- 20304481 TI - The use of decellularized adipose tissue to provide an inductive microenvironment for the adipogenic differentiation of human adipose-derived stem cells. AB - The development of an engineered adipose tissue substitute, capable of supporting reliable, predictable, and complete fat tissue formation, would be of significant value in the fields of plastic and reconstructive surgery. Towards the goal of engineering an optimized microenvironment for adipogenesis, a decellularization strategy was developed for adipose tissue, which yielded 3-D scaffolds with preserved extracellular matrix architecture. A significant volume of scaffolding material could be obtained from a human tissue source that is commonly discarded. Histology, immunohistochemistry, and scanning electron microscopy confirmed the efficacy and reproducibility of the approach, and also indicated that the basement membrane was conserved in the processed matrix, including laminin and collagen type IV. Seeding experiments with human adipose-derived stem cells indicated that the decellularized adipose tissue (DAT) provided an inductive microenvironment for adipogenesis, supporting the expression of the master regulators PPARgamma and CEBPalpha, without the need for exogenous differentiation factors. High levels of adipogenic gene expression and glycerol-3 phosphate dehydrogenase activity were observed in the induced DAT scaffolds, as compared to cells grown in monolayer or cell aggregate culture. The protein data emphasized the importance of the cell donor source in the development of tissue engineering strategies for large-volume soft tissue regeneration. PMID- 20304480 TI - Synergistic effects of tethered growth factors and adhesion ligands on DNA synthesis and function of primary hepatocytes cultured on soft synthetic hydrogels. AB - The composition, presentation, and spatial orientation of extracellular matrix molecules and growth factors are key regulators of cell behavior. Here, we used self-assembling peptide nanofiber gels as a modular scaffold to investigate how fibronectin-derived adhesion ligands and different modes of epidermal growth factor (EGF) presentation synergistically regulate multiple facets of primary rat hepatocyte behavior in the context of a soft gel. In the presence of soluble EGF, inclusion of dimeric RGD and the heparin binding domain from fibronectin (HB) increased hepatocyte aggregation, spreading, and metabolic function compared to unmodified gels or gels modified with a single motif, but unlike rigid substrates, gels failed to induce DNA synthesis. Tethered EGF dramatically stimulated cell aggregation and spreading under all adhesive ligand conditions and also preserved metabolic function. Surprisingly, tethered EGF elicited DNA synthesis on gels with RGD and HB. Phenotypic differences between soluble and tethered EGF stimulation of cells on peptide gels are correlated with differences in expression and phosphorylation the EGF receptor and its heterodimerization partner ErbB2, and activation of the downstream signaling node ERK1/2. These modular matrices reveal new facets of hepatocellular biology in culture and may be more broadly useful in culture of other soft tissues. PMID- 20304482 TI - Modulation of gene expression and collagen production of anterior cruciate ligament cells through cell shape changes on polycaprolactone/chitosan blends. AB - Our previous study has illustrated that chitosan could enhance human anterior cruciate ligament (ACL) cells to exhibit a dramatic effect on increasing the gene expression of transforming growth factor beta1 (TGF-beta1), which is a specific gene for wound healing and collagen synthesis. However, human ACL cells could not adhere and proliferate well on chitosan. In order to overcome this drawback, we introduced polycaprolactone (PCL) into chitosan by the method of blending in this study. It was found that the morphology, viability and gene expression of human ACL cells on the chitosan/PCL blends could be effectively regulated. With the increase of PCL content in blends, human ACL cells presented more flatten shape, well-organized cytoskeleton, and higher proliferated ability. Compared to flatten shape, human ACL cells with round shape exhibited higher levels of mRNA expression of TGF-beta1 and collagen type III through 3-day culture period. Furthermore, these blended materials could upregulate protein synthesis of human ACL cells, which corresponded to their gene expressions. Therefore, it is possible to combine the advantages of chitosan and PCL to create a new blended material, which could control cellular morphologies specifically, and further to regulate the gene expression and protein production of cells for specific applications. We expected this concept, controlling the cell shape through biomaterial to modulate the behavior of cells, could provide a new vision for the material selection of ligament tissue engineering. PMID- 20304483 TI - Enhanced transfection with silica-coated polyplexes loading plasmid DNA. AB - Silica-coating of positively charged polyplexes was demonstrated through silicic acid condensation to improve the polyplexes for enhanced complex stability and transfection efficiency. Silicic acid was efficiently condensed by polycations to form a silica network in the polyplex through electrostatic interaction and hydrogen bonding. The silica-coated (SC) polyplexes had an anionic surface charge of -20 mV and were 10-20 nm larger in size compared to the non-silica-coated control (+33.4 mV, 106 nm). Silica-coating significantly improved the polyplex stability against both dissociations by counter polyanion exchange and aggregation by salt. The silica network was dissolved to form silicic acid by removing free silicic acid based on the equilibrium, SiO(2) + 2H(2)O right arrow over left arrow Si(OH)(4). Indeed, dialysis of the SC polyplex solution against excess silica-free buffer permitted plasmid DNA release from the silica-coated polyplex, indicating the reversible nature of the silica-layer. The SC polyplex achieved significantly higher transfection efficiency without serious cytotoxicity compared to the polyplex without silica-coating. Detailed examinations of transfection using SC polyplexes revealed that the enhanced transfection efficiency was because of facilitated endosomal escape, possibly due to the protonation of the silica in acidic endosomal compartments. These findings demonstrate the utility of the silica-coating technique for polyplex-mediated gene delivery. PMID- 20304484 TI - Fibrin-polylactide-based tissue-engineered vascular graft in the arterial circulation. AB - There is a clear clinical requirement for the design and development of living, functional, small-calibre arterial grafts. Here, we investigate the potential use of a small diameter, tissue-engineered artery in a pre-clinical study in the carotid artery position of sheep. Small-calibre ( approximately 5 mm) vascular composite grafts were molded using a fibrin scaffold supported by a poly(L/D)lactide 96/4 (P(L/D)LA 96/4) mesh, and seeded with autologous arterial derived cells prior to 28 days of dynamic conditioning. Conditioned grafts were subsequently implanted for up to 6 months as interposed carotid artery grafts in the same animals from which the cells were harvested. Explanted grafts (n = 6) were patent in each of the study groups (1 month, 3 months, 6 months), with a significant stenosis in one explant (3 months). There was a complete absence of thrombus formation on the luminal surface of grafts, with no evidence for aneurysm formation or calcification after 6 months in vivo. Histological analyses revealed remodeling of the fibrin scaffold with mature autologous proteins, and excellent cell distribution within the graft wall. Positive vWf and eNOS staining, in addition to scanning electron microscopy, revealed a confluent monolayer of endothelial cells lining the luminal surface of the grafts. The present study demonstrates the successful production and mid-term application of an autologous, fibrin-based small-calibre vascular graft in the arterial circulation, and highlights the potential for the creation of autologous implantable arterial grafts in a number of settings. PMID- 20304485 TI - Neuronal polarity selection by topography-induced focal adhesion control. AB - Interaction between differentiating neurons and the extracellular environment guides the establishment of cell polarity during nervous system development. Developing neurons read the physical properties of the local substrate in a contact-dependent manner and retrieve essential guidance cues. In previous works we demonstrated that PC12 cell interaction with nanogratings (alternating lines of ridges and grooves of submicron size) promotes bipolarity and alignment to the substrate topography. Here, we investigate the role of focal adhesions, cell contractility, and actin dynamics in this process. Exploiting nanoimprint lithography techniques and a cyclic olefin copolymer, we engineered biocompatible nanostructured substrates designed for high-resolution live-cell microscopy. Our results reveal that neuronal polarization and contact guidance are based on a geometrical constraint of focal adhesions resulting in an angular modulation of their maturation and persistence. We report on ROCK1/2-myosin-II pathway activity and demonstrate that ROCK-mediated contractility contributes to polarity selection during neuronal differentiation. Importantly, the selection process confined the generation of actin-supported membrane protrusions and the initiation of new neurites at the poles. Maintenance of the established polarity was independent from NGF stimulation. Altogether our results imply that focal adhesions and cell contractility stably link the topographical configuration of the extracellular environment to a corresponding neuronal polarity state. PMID- 20304486 TI - Expression of AT1R, AT2R and AT4R and their roles in extravillous trophoblast invasion in the human. AB - The placental renin-angiotensin system (RAS) is active from early pregnancy and may have a role in placentation. Angiotensin II (AngII) acts via binding to receptor types AT1R and AT2R. Recently smaller peptide members of the angiotensin family have been recognised as having biological relevance. Angiotensin (3-8) (AngIV) has a specific receptor (AT4R) and evokes hypertrophy, vasodilatation and vascular inflammatory response. The aim of this study was to characterise placental expression of AT1R, AT2R and AT4R, and to determine whether AngII and AngIV regulate extravillous trophoblast (EVT) invasion, apoptosis and proliferation. Placental samples were obtained from women undergoing elective surgical termination of pregnancy (TOP) at 8-10 weeks gestation (early TOP), 12 14 weeks gestation (mid TOP) or at delivery following normal pregnancy or with pre-eclampsia (PE). Immunohistochemistry and qRT-PCR were performed to determine placental mRNA and protein expression of AT1R, AT2R and AT4R at all gestational ages. EVT invasion following culture with AngII or AngIV was assessed in early placental tissue using Matrigel invasion assays. Invasion was assessed on day 6 of culture and placental explants were harvested for immunohistochemical analysis of apoptosis and proliferation. The results from qRT-PCR and immunohistochemistry showed placental AT1R expression which did not vary with gestation. The highest levels of expression of AT2R were found in early and mid TOP placentae compared to term pregnancy. Expression of AT4R was increased in term placentae, with a significant reduction in PE placentae. Moreover, culture with AngIV or AngII increased EVT invasion from placental explants, which showed increased trophoblast proliferation and reduced apoptosis. This study has characterised expression of AT4R and AT1R and AT2R in human placenta throughout normal pregnancy and in PE. Both AngIV and AngII may play an important role in normal pregnancy. PMID- 20304487 TI - Intrinsic calcium dynamics control botulinum toxin A susceptibility in distinct neuronal populations. AB - SNAP-25 is a SNARE protein implicated in exocytosis and in the negative modulation of voltage-gated calcium channels. We have previously shown that GABAergic synapses, which express SNAP-25 at much lower levels relative to glutamatergic ones, are characterized by a higher calcium responsiveness to depolarization and are largely resistant to botulinum toxin A. We show here that silencing of SNAP-25 in glutamatergic neurons, a procedure which increases KCl induced calcium elevations, confers these synapses with toxin resistance. Since it is known that calcium reverts the efficacy of botulinum A, we investigated whether the lower effectiveness of the toxin in inhibiting GABAergic vesicle cycling might be attributable to higher evoked calcium transients of inhibitory neurons. We demonstrate that either expression of SNAP-25(1-197) or BAPTA/AM treatment, both inhibiting calcium dynamics, facilitate block of GABAergic vesicle exocytosis upon toxin treatment. These data indicate that intrinsic calcium dynamics control botulinum A susceptibility in distinct neuronal populations. PMID- 20304488 TI - Mutational analysis of K-ras codon 12 in blood samples of patients with acute myeloid leukemia. AB - Mutations in K-ras are frequent in acute myeloid leukemia (AML). The association of these mutations to clinical features and their prognostic value are unclear. We used quantitative PCR with peptide nucleic acid mediated PCR clamping to specifically analyze 257 blood samples of 31 AML patients for K-ras codon 12 alterations. A total of 20 samples of nine patients harbored a K-ras mutation. The most frequent mutation was the GTT variant which causes an amino acid exchange from glycine to valine. Correlation with clinical data suggests K-ras mutations to be associated with higher age and a better response to anti-leukemic chemotherapy. PMID- 20304489 TI - Trauma focused CBT for children with co-occurring trauma and behavior problems. AB - OBJECTIVE: Childhood trauma impacts multiple domains of functioning including behavior. Traumatized children commonly have behavioral problems that therapists must effectively evaluate and manage in the context of providing trauma-focused treatment. This manuscript describes practical strategies for managing behavior problems in the context of trauma-focused evidence-based treatment (EBT) using a commonly implemented EBT for traumatized children. METHODS: The empirical literature is reviewed and practical strategies are described for conducting trauma- and behavioral-focused assessments; engaging families in trauma- and behavioral-focused treatment; treatment-planning that includes a balance of both trauma and behavioral foci; managing ongoing behavioral problems in the context of providing trauma-focused treatment; managing behavioral crises ("crises of the week"); addressing overwhelming family or social problems; and steps for knowledge transfer. RESULTS: Trauma-focused EBT that integrate behavioral management strategies can effectively manage the behavioral regulation problems that commonly occur in traumatized children. CONCLUSIONS: Addressing trauma related behavioral problems is an important part of trauma-focused treatment and is feasible to do in the context of using common trauma-focused EBT. PRACTICE IMPLICATIONS: Integrating effective behavioral interventions into trauma-focused EBT is essential due to the common nature of behavioral regulation difficulties in traumatized children. PMID- 20304490 TI - Peer victimization and internalizing problems in children: a meta-analysis of longitudinal studies. AB - OBJECTIVE: A recent meta-analytic review of cross-sectional studies examining correlations between peer victimization and indices of internalizing problems indicates that victims of bullying are highly distressed. However, the reliance on cross-sectional studies precludes interpretation of the direction of effects. The present study was designed to investigate if internalizing problems are antecedents of victimization, consequences of victimization, or both. METHOD: This paper provides a meta-analysis of 18 longitudinal studies examining prospective linkages between peer victimization and internalizing problems (n=13,978). Two prospective paths were examined: the extent to which peer victimization at baseline predicts changes in internalizing problems, as well as the extent to which internalizing problems at baseline predict changes in peer victimization. RESULTS: Results revealed significant associations between peer victimization and subsequent changes in internalizing problems, as well as significant associations between internalizing problems and subsequent changes in peer victimization. Several moderator effects were observed. CONCLUSIONS: Internalizing problems function as both antecedents and consequences of peer victimization. These reciprocal influences suggest a vicious cycle that contributes to the high stability of peer victimization. PRACTICE IMPLICATIONS: This study should further encourage steps to reduce bullying at schools. PMID- 20304491 TI - Child maltreatment fatalities in children under 5: Findings from the National Violence Death Reporting System. AB - OBJECTIVE: To describe the distribution of child maltreatment fatalities of children under 5 by age, sex, race/ethnicity, type of maltreatment, and relationship to alleged perpetrator using data from the National Violent Death Reporting System (NVDRS). STUDY DESIGN: Two independent coders reviewed information from death certificates, medical examiner and police reports corresponding to all deaths in children less than 5 years of age reported to NVDRS in 16 states. RESULTS: Of the 1,374 deaths for children under 5 reported to NVDRS, 600 were considered attributable to child maltreatment. Over a half of the 600 victims of child maltreatment in this age group were under 1 year old, 59% were male, 42% non-Hispanic Whites, and 38% were non-Hispanic Blacks. Two thirds of child maltreatment fatalities in children under 5 were classified as being due to abusive head trauma (AHT), 27.5% as other types of physical abuse, and 10% as neglect. Based on these data, fathers or their substitutes were significantly more likely than mothers to be identified as alleged perpetrators for AHT and other types of physical abuse, while mothers were more likely to be assigned responsibility for neglect. CONCLUSIONS: Among children under 5 years, children under 1 are the main age group contributing to child maltreatment fatalities in the NVDRS. AHT is the main cause of death in these data. These findings are limited by underascertainment of cases and fair inter-rater reliability of coding. PRACTICE IMPLICATIONS: The findings suggest the need to develop and evaluate interventions targeting AHT to reduce the overall number of child maltreatment deaths in young children. These interventions should make special efforts to include fathers and their substitutes. PMID- 20304492 TI - Psychological distress as a risk factor for re-victimization in children. AB - OBJECTIVE: The goal of this study is to examine the role of psychological distress in predicting child re-victimization across various forms including conventional crime, peer/sibling violence, maltreatment, sexual violence, and witnessed violence. METHODS: Longitudinal data from the Developmental Victimization Survey, which surveyed children between the ages of 2 and 17 using random digit dial (RDD) methodology, was used to ask about child victimization and psychological distress. The sample for this analysis was 1,025 children who had experienced at least one form of victimization in the first wave of data collection. RESULTS: Results show that psychological distress (defined as a composite score of the depression, anger, and anxiety scales) was a unique significant predictor of subsequent overall victimization, as well as victimization across the different categories of victimization (conventional crime, maltreatment, peer and sibling victimization, sexual victimization, and witnessed/indirect victimization), while controlling for demographic variables and prior year victimization. CONCLUSIONS: These results suggest that the psychological consequences of victimization may also serve as precipitants for re victimization. We discuss the implications this may have on the understanding of the psychological sequelae of victimization and its role in the risk of future victimization. PRACTICE IMPLICATIONS: This research suggests that practitioners should expand the forms of victimization that are assessed when working with victimized children. Treatment should not only focus on alleviating psychological distress, but also on the role it may play in raising the risk for re victimization. Treatment providers should be attentive to bolstering protective qualities when treating victimized children. PMID- 20304493 TI - The impact of childhood abuse history and domestic violence on the mental health of women in Japan. AB - OBJECTIVE: To understand the independent and interactive effects of childhood abuse history (CAH) and domestic violence (DV) on the mental health status of women in Japan. METHODS: A self-administered questionnaire survey was conducted among a sample of 340 women staying in 83 Mother-Child Homes in Japan to assess the women's CAH and DV experiences, along with their current mental health problems, including dissociated, depressed, and traumatic symptoms. RESULTS: Independent from DV, CAH, especially psychological abuse, had a significant impact on all of the women's mental health symptoms. DV was found to have an independent effect on traumatic symptoms. Weak interactive effects of CAH and DV were found on dissociated and traumatic symptoms. Among those women without CAH, DV was significantly associated with dissociated and traumatic symptoms; however, DV had no impact on dissociated and traumatic symptoms if CAH was present. CONCLUSIONS: The findings suggest the significant impact of CAH on women's mental health problems, independent from DV. CAH and DV weakly interact on women's mental health. PRACTICE IMPLICATIONS: In psychological therapy for battered women with mental health problems, if the cases were abused during childhood, it is recommended that therapy be focused on childhood abuse, especially if the client was psychologically abused. In addition, mental health care and welfare providers should be aware that the mental health problems of mothers without CAH might be exacerbated by DV; thus, appropriate resource allocation should be considered. PMID- 20304494 TI - Bioaccessibility of trace metals in boat paint particles. AB - A ground composite of paint fragments collected from a leisure boatyard has been analysed for total and bioaccessible trace metal concentrations. The sample contained concentrations of Cu and Zn of about 1% due to their use in antifouling formulations, and significant quantities of Ba, Cd, Cr, Ni, Pb, Sb and Sn. In a simulated stomach phase (pH 2.5), bioaccessible concentrations relative to respective total concentrations ranged from G, p.Tyr899Asp). We used the polymorphic CFH variant p.His402Tyr to track expression of p.Tyr899Asp, and found that this mutant was expressed in minimal quantities in serum. In the one affected individual we found a second CFH mutation (c.3581G>A, p.Gly1194Asp) on the other allele which was expressed normally. We showed that this mutant, which has been described previously in aHUS, has impaired regulation of cell surface complement activation. The affected individual in this family is therefore a compound heterozygote for two functionally significant CFH mutations. Two individuals (mother and male sib) in the pedigree carried only c.2768T>G, p.Tyr899Asp and one (father) carried only c.3581G>A, p.Gly1194Asp, and all three were asymptomatic. Thus, further investigation of this family has enabled us to clarify the genotype-phenotype correlation. PMID- 20304498 TI - Peptidoglycan, not endotoxin, is the key mediator of cytokine gene expression induced in rainbow trout macrophages by crude LPS. AB - In rainbow trout macrophages, phenol-extracted lipopolysaccharide (LPS) preparations stimulate proinflammatory cytokine gene expression but ultrapure preparations of LPS are inactive. Crude LPS preparations could potentially have a number of contaminants including peptidoglycans (PGNs), nucleic acids and lipoproteins. Thus, in the current study we individually tested potentially contaminating pathogen associated molecular patterns (PAMPs) on rainbow trout (Oncorhynchus mykiss) macrophages to determine which ones could induce proinflammatory cytokine expression. We found that PGNs derived from Gram negative bacteria (Escherichia coli 0111:B4 and K12), are potent inducers of IL 1beta and IL-6 gene expression and were equal to, or more potent than, crude LPS. On the other hand, PGNs of Gram-positive bacteria, DNA, RNA and lipoteichoic acid were weak stimulators, and lipid A, lipoprotein (Pam3CSK4) and ultrapure LPS were nonstimulatory. More importantly, crude LPS treated with lysozyme to degrade PGNs, exhibited greatly reduced activity in stimulating IL-1beta and IL-6 gene expression, indicating that PGNs in the crude LPS are responsible for a significant amount of the proinflammatory activity. Finally, we showed that PGN treatment induces expression of COX-2 and the subsequent synthesis and release of prostaglandin E(2) (PGE(2)), an important mediator of inflammatory processes. The strong stimulatory effect of E. coli PGNs by themselves on trout macrophages suggests that the recognition of Gram-negative bacteria in trout is through PGNs in the bacterial wall, and indicates that the systems responsible for bacterial recognition in invertebrates (e.g., Drosophila) may also be conserved in some vertebrates. PMID- 20304499 TI - Treatment of dry eye syndrome with orally administered CF101: data from a phase 2 clinical trial. AB - OBJECTIVE: To explore the safety and efficacy of CF101, an A(3) adenosine receptor agonist, in patients with moderate to severe dry eye syndrome. DESIGN: Phase 2, multicenter, randomized, double-masked, placebo-controlled, parallel group study. PARTICIPANTS: Sixty-eight patients completed the study, 35 patients in the placebo group and 33 patients in the CF101 group. INTERVENTION: Patients were treated orally with either 1 mg CF101 pills or matching vehicle-filled placebo pills, given twice daily for 12 weeks, followed by a 2-week posttreatment observation. MAIN OUTCOME MEASURES: An improvement of more than 25% over baseline at week 12 in one of the following parameters: (1) tear break-up time (BUT); (2) superficial punctate keratitis assessed by fluorescein staining results; and (3) Schirmer tear test 1 results. Clinical laboratory safety tests, ophthalmic examinations, intraocular pressure (IOP) measurements, electrocardiographic evaluations, vital sign measurements, and monitoring of adverse events. RESULTS: A statistically significant increase in the proportion of patients who achieved more than 25% improvement in the corneal staining and in the clearance of corneal staining was noted between the CF101-treated group and the placebo group. Treatment with CF101 resulted in a statistically significant improvement in the mean change from baseline at week 12 of the corneal staining, BUT, and tear meniscus (TM) height in the CF101-treated group. CF101 was well tolerated and exhibited an excellent safety profile with no serious adverse events. A statistically significant decrease from baseline was observed in the IOP of the CF101-treated group in comparison with the placebo group. CONCLUSIONS: CF101, given orally, induced a statistically significant improvement in the corneal staining and an improvement in the BUT and TM in patients with moderate to severe dry eye syndrome. The drug was very well tolerated. These data and the anti inflammatory characteristic of CF101 support further study of the drug as a potential treatment for the signs and symptoms of dry eye syndrome. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references. PMID- 20304500 TI - Platinum(II) oxalato complexes with adenine-based carrier ligands showing significant in vitro antitumor activity. AB - [Pt(L)(2)(ox)] (1), [Pt(2-OMeL)(2)(ox)] (2), [Pt(3-OMeL)(2)(ox)] (3), [Pt(2,3 diOMeL)(2)(ox)] (4), [Pt(2,4-diOMeL)(2)(ox)] (5), [Pt(3,4-diOMeL)(2)(ox)] (6) and [Pt(3,5-diOMeL)(2)(ox)].4H(2)O (7) platinum(II) oxalato (ox) complexes were synthesized using the reaction of potassium bis(oxalato)platinate(II) dihydrate with 2-chloro-N6-(benzyl)-9-isopropyladenine or its benzyl-substituted analogues (nL). The complexes 1-7, which represent the first platinum(II) oxalato complexes involving adenine-based ligands, were fully characterized by various physical methods including multinuclear and two dimensional NMR spectroscopy. A single crystal X-ray analysis of [Pt(2,4-diOMeL)(2)(ox)].2DMF (5.2DMF; DMF=N,N' dimethylformamide), proved the slightly distorted square-planar geometry in the vicinity of the Pt(II) ion with one bidentate-coordinated oxalate dianion and two adenine derivatives (nL) coordinated to the Pt(II) centre through the N7 atom of an adenine moiety, thereby giving a PtN(2)O(2) donor set. In vitro cytotoxicity of the prepared complexes was tested by an MTT assay against osteosarcoma (HOS) and breast adenocarcinoma (MCF7) human cancer cell lines. The best results were achieved for the complexes 2 and 5 in the case of both cell lines, whose IC(50) values equalled 3.6+/-1.0, and 4.3+/-2.1microM (for 2), and 5.4+/-3.8, and 3.6+/ 2.1microM (for 5), respectively. The IC(50) equals 9.2+/-1.5microM against MCF7 cells in the case of 1. The in vitro cytotoxicity of the mentioned complexes significantly exceeded commercially used platinum-based anticancer drugs cisplatin (34.2+/-6.4microM and 19.6+/-4.3microM) and oxaliplatin (>50.0microM for both cancer cell lines). PMID- 20304501 TI - The specificity of childhood adversities and negative life events across the life span to anxiety and depressive disorders. AB - BACKGROUND: Although several studies have shown that life adversities play an important role in the etiology and maintenance of both depressive and anxiety disorders, little is known about the relative specificity of several types of life adversities to different forms of depressive and anxiety disorder and the concurrent role of neuroticism. Few studies have investigated whether clustering of life adversities or comorbidity of psychiatric disorders critically influence these relationships. METHODS: Using data from the Netherlands Study of Depression and Anxiety (NESDA), we analyzed the association of childhood adversities and negative life experiences across the lifespan with lifetime DSM-IV-based diagnoses of depression or anxiety among 2288 participants with at least one affective disorder. RESULTS: Controlling for comorbidity and clustering of adversities the association of childhood adversity with affective disorders was greater than that of negative life events across the life span with affective disorders. Among childhood adversities, emotional neglect was specifically associated with depressive disorder, dysthymia, and social phobia. Persons with a history of emotional neglect and sexual abuse were more likely to develop more than one lifetime affective disorder. Neuroticism and current affective disorder did not affect the adversity-disorder relationships found. LIMITATIONS: Using a retrospective study design, causal interpretations of the relationships found are not warranted. CONCLUSIONS: Emotional neglect seems to be differentially related to depression, dysthymia and social phobia. This knowledge may help to reduce underestimation of the impact of emotional abuse and lead to better recognition and treatment to prevent long-term disorders. PMID- 20304502 TI - Low dose lignocaine added to propofol does not attenuate the response to electroconvulsive therapy. AB - BACKGROUND: The addition of small amounts of lignocaine (50 mg) to propofol (200 mg) has been previously shown to reduce pain in injection, a common problem with this particular anaesthetic agent. The aim of this study was to investigate whether using the mixture of propofol plus lignocaine had any adverse effects on ECT seizure expression (duration, and ictal quality). METHOD: Ictal EEG records were retrospectively examined in 29 patients who underwent 80 pairs of ECT treatments, one given with propofol alone and one with propofol plus lignocaine. Ictal quality was manually rated for the transition from the polyspike phase to the slow wave phase, amplitude of the mid-ictal spike-and-wave phase, regularity of morphology of the predominant pattern of the slow wave phase, stereotypy, variability of the morphology and amplitude of the slow wave phase and post-ictal suppression. RESULTS: There was no significant difference in seizure duration between the two groups (33.4+/-13.0 s (propofol) vs. 33.6+/-11.2 s (propofol plus lignocaine). Furthermore although the addition of lignocaine delayed the onset of the slow wave phase by about 1s, it resulted in an improvement in three of four of the other measures of ictal quality. CONCLUSION: The addition of a small dose of lignocaine to propofol during ECT treatment enhanced rather than reduced the quality of the seizures produced. PMID- 20304503 TI - Correlation between patient and clinician assessments of depression severity in the PREVENT study. AB - BACKGROUND: The degree of agreement between patient- and clinician-rated scales of depressive severity varies widely. This study analyzed agreement between commonly used depression rating scales in the Prevention of Recurrent Episodes of Depression with Venlafaxine Extended Release (ER) for Two Years (PREVENT) trial. METHODS: The PREVENT trial was a multiphase, randomized, double-blind study of patients with recurrent major depressive disorder. This secondary analysis evaluated acute (10weeks) and continuation phase (6months) data. Pearson correlation coefficients at each acute-phase (weekly) and continuation-phase (monthly) visit were calculated for patient-rated (30-item Inventory of Depressive Symptomatology-Self-Rated [IDS-SR30] and clinician-rated (17-item Hamilton Rating Scale for Depression [HAM-D17] and Clinical Global Impressions Severity [CGI-S]) measures and for response and remission. RESULTS: Data from 1,047 patients were analyzed. The respective correlation coefficients at baseline, week 10, and month 6 were: IDS-SR30: HAM-D17: 0.46, 0.75, 0.70; and for IDS-SR30: CGI-S 0.28, 0.67, 0.65. Agreement between IDS-SR30- and HAM-D17-defined remission and response was relatively poor: week 10, 0.52 and 0.34, respectively; month 6, 0.45 and 0.32, respectively. CONCLUSIONS: These findings suggest that patient-rated measures of depression severity do not correspond strongly with clinician ratings, and are particularly poor prior to the initiation of treatment. PMID- 20304504 TI - Psychotic symptoms with sexual content in the "ultra high risk" for psychosis population: frequency and association with sexual trauma. AB - Individuals at "ultra high risk" (UHR) for psychosis have been found to experience high rates of sexual trauma. An aetiological role for sexual trauma has been proposed for psychotic disorders and may influence psychotic symptom content. We aimed to investigate the relationship between previous sexual trauma and reported psychotic-like experiences, in particular psychotic symptoms with a sexual content in a UHR sample. We investigated the prevalence of "attenuated" or "subthreshold" psychotic symptoms with a sexual content in a consecutive series of patients recruited to a specialist UHR clinic. Patient's experience of general and sexual trauma was rated separately using a trauma questionnaire based on the list of events qualifying as traumas under DSM IV. The sample consisted of 92 patients, 14 (15.2%) had experienced an attenuated psychotic symptom with sexual content. The most common symptom was overvalued ideas/delusions of being watched in the shower/toilet or undressing. A considerable proportion of the sample (36.2%) had experienced sexual trauma (sexually molested or raped). Presence of attenuated psychotic symptoms with sexual content was related to history of previous sexual trauma (OR 7.17, P<0.01). This relationship remained significant when other traumatic experiences, PTSD diagnosis, age and sex were adjusted for. Further research into this relationship with regard to outcome and treatment is warranted. PMID- 20304505 TI - A functional polymorphism (Ser326Cys) of the human 8-oxoguanine DNA glycosylase (hOGG1) gene and schizophrenia. PMID- 20304506 TI - Haloperidol induces higher Homer1a expression than risperidone, olanzapine and sulpiride in striatal sub-regions. AB - Homer1a and Yotiao are two post-synaptic density proteins at the crossroad of dopamine-glutamate neurotransmission. Homer1a has been implicated in the pathophysiology of schizophrenia and is differentially induced by typical and atypical antipsychotics, perhaps according to their dopaminergic profile. Yotiao has been involved in glutamate and dopamine post-synaptic signalling. Here, we seek to determine whether Homer1a and Yotiao might be implicated in post-synaptic response to antipsychotics with affinity to different dopamine D(2) receptors: haloperidol (0.8mg kg(-1)), risperidone (3mg kg(-1)), olanzapine (2.5mg kg(-1)) and (-)-sulpiride (50mg kg(-1)). Homer1a expression was significantly induced by haloperidol compared to vehicle and to atypical antipsychotics in almost all striatal sub-regions. Atypical antipsychotics induced the gene in the lateral putamen and in the core of the accumbens only. All antipsychotics, with the exclusion of sulpiride, elicited a dorsolateral-to-ventromedial distribution pattern of Homer1a expression. No significant induction was detected for Yotiao. These results suggest that the quantitative and topographical pattern of Homer1a expression may putatively be related to antipsychotics affinity and/or occupancy at dopamine D(2) receptors. PMID- 20304507 TI - Quality of life and functional capacity can be improved in patients with Eisenmenger syndrome with oral sildenafil therapy. AB - BACKGROUND: Patients with Eisenmenger syndrome (ES) have a decreased exercise capacity and poor quality of life (QoL). While patients may survive to middle adulthood, the burden of disease is disabling. Sildenafil seems to improve exercise tolerance and hemodynamics, but there is no data to date on its impact on QoL. METHODS: Eisenmenger patients in New York Heart Association (NYHA) class III were recruited in a prospective study of efficacy and safety of oral sildenafil. The QoL endpoint was assessed using a disease-specific questionnaire (CAMPHOR). Exercise capacity was assessed by means of six minute walk test (6MWT). All patients underwent comprehensive assessment at baseline and after 3months of treatment. RESULTS: Twelve patients (mean age was 34.3+/-10.2, 83% female) with various cardiac anatomies were recruited. No major adverse events during the follow-up or significant drop in resting oxygen saturation were recorded. After 3months of oral sildenafil therapy, all patients improved to NYHA II with a concomitant improvement in 6MWT distance (347.3+/-80.7 to 392.5+/ 82.0m, p=0.002). All components of the CAMPHOR score, relating to symptoms, activity and QoL, improved significantly resulting in substantial improvement in the total CAMPHOR score (27.6+/-10.5 to 15.8+/-10.4, p=0.002). CONCLUSIONS: Three months of sildenafil therapy in adults with ES was well tolerated and associated with significant improvement in the QoL CAMPHOR questionnaire and in NYHA class and exercise capacity. Larger studies are warranted to assess long term efficacy of oral sildenafil and potential impact on survival. PMID- 20304508 TI - A stochastic risk-analysis model for the spread of bovine viral diarrhea virus after introduction to naive cow-calf herds. AB - A stochastic SIR model was developed to simulate the spread of bovine viral diarrhea virus (BVDV) through a cow-calf herd and estimate the effect of the virus on the herd, including abortions, calf morbidity, and calf mortality. The model was applied with three herd sizes (400, 100, and 50 head) and four control strategies (no intervention, vaccination of breeding stock, testing all calves pre-breeding and culling of persistently infected calves, and both vaccination of adults and testing and culling of calves). When no control strategy was implemented the BVDV reproductive rate (R(E-PI)) of persistently infected calves (PI's), vertical transmission rate from cows to calves and the mortality rate of PI's were influential in the number of PI's produced in the herd. When a vaccination program alone was implemented the vaccine efficacy was influential in the number of PI's produced in the herd. All control strategies decreased the effects of BVDV on the herd at both 1 and 10 years compared to no control. In most cases the combination of adult vaccination and calf testing and culling resulted in the largest decrease in the both the median and 95% prediction interval for the range of effects from BVDV. The effect of control strategies was most apparent in the 400 head herds. All control strategies increased the probability of early clearance of PI's from the herd for all herd sizes. Fifty and 100 head herds cleared infection by 4 and 9 years respectively even without a control program but 400 head herds did not always clear infection after 10 years unless a testing program was implemented. The model presented is valuable in assessing the effect of control strategies and the effects of disease parameters on BVDV spread in beef herds. PMID- 20304510 TI - A limited-sample benchmark approach to assess and improve the performance of risk equalization models. AB - A new method is proposed to assess and improve the performance of risk equalization models in competitive markets for individual health insurance, where compensation is intended for variation in observed expenditures due to so-called S(ubsidy)-type risk factors but not for variation due to other, so-called N(on subsidy)-type risk factors. Given the availability of a rich subsample of individuals for which normative expenditures, Y(NORM), can be accurately determined, we make two contributions: (a) any risk equalization scheme applied to the entire population, Y(REF), should be evaluated through its performance in the subsample, by comparing Y(REF) with Y(NORM) (not by comparing Y(REF) with observed expenditures, Y, in the entire population, as commonly done); (b) conventional risk equalization schemes can be improved by the subsample regression of Y(NORM), rather than Y, on the risk adjusters that are observable in the entire population. This new method is illustrated by an application to the 2004 Dutch risk equalization model. PMID- 20304509 TI - The control of Corynebacterium pseudotuberculosis infection in sheep flocks: a mathematical model of the impact of vaccination, serological testing, clinical examination and lancing of abscesses. AB - A mathematical model of Corynebacterium pseudotuberculosis infection in sheep flocks was used to evaluate strategies for control and elimination of caseous lymphadenitis (CLA). Control strategies tested were vaccination, serological testing and removal of seropositives, clinical examination and removal of sheep with abscesses, lancing abscesses, and appropriate combinations. Three different infection rates with and without replacement of culled ewes were used to evaluate the control options. Controls were either implemented immediately after infection was detected in a flock or once CLA was at endemic equilibrium, and with different frequencies of examination or testing. Elimination of infection was defined as 99% confidence that no sheep were infected with C. pseudotuberculosis. The control strategies were evaluated by estimating the reduction in infection or probability of elimination and the number of ewes culled from the flock. Lancing abscesses reduced the prevalence of infection when the initial prevalence was <0.60, but elimination was unlikely. A vaccine efficacy of 0.79 or more led to elimination of infection from the flock, provided that the endemic prevalence of infection was <0.60. A combination of vaccination and clinical examination reduced the prevalence of infection at a faster rate than using clinical examination or vaccination alone where five rounds of clinical examination were done. Serological testing led to elimination of infection after five tests, but was highly dependent upon the diagnostic test sensitivity and specificity and management options used: a test sensitivity of 0.90 always resulted in elimination. A test specificity greater than 0.90 prevented removal of many false positive ewes and consequently prevented a large reduction in lamb production. Elimination was most likely using a serological test with sensitivity and specificity >0.90, but vaccination combined with clinical examination reduced infection rapidly with little impact on lamb productivity. Further research is required to develop a diagnostic test with at least 0.90 specificity and sensitivity under field conditions before any methods of control can be recommended with confidence. PMID- 20304511 TI - Recent advances in large-scale production of monoclonal antibodies and related proteins. AB - The rapid development of high-yielding and robust manufacturing processes for monoclonal antibodies is an area of significant focus in the biopharmaceutical landscape. Advances in mammalian cell culture have taken titers to beyond the 5 g/l mark. Platform approaches to downstream process development have become widely established. Continuous evolution of these platforms is occurring as experience with a wider range of products is accrued. The increased cell culture productivity has shifted the attention of bioprocess development to operations downstream of the production bioreactor. This has rejuvenated interest in the use of non-chromatographic separation processes. Here, we review the current state-of the-art industrial production processes, focusing on downstream technologies, for antibodies and antibody-related products and discuss future avenues for evolution. PMID- 20304512 TI - Comparison of optimized single and multifield irradiation plans of antiproton, proton and carbon ion beams. AB - BACKGROUND AND PURPOSE: Antiprotons have been suggested as a possibly superior modality for radiotherapy, due to the energy released when antiprotons annihilate, which enhances the Bragg peak and introduces a high-LET component to the dose. However, concerns are expressed about the inferior lateral dose distribution caused by the annihilation products. METHODS: We use the Monte Carlo code FLUKA to generate depth-dose kernels for protons, antiprotons, and carbon ions. Using these we then build virtual treatment plans optimized according to ICRU recommendations for the different beam modalities, which then are recalculated with FLUKA. Dose-volume histograms generated from these plans can be used to compare the different irradiations. RESULTS: The enhancement in physical and possibly biological dose from annihilating antiprotons can significantly lower the dose in the entrance channel; but only at the expense of a diffuse low dose background from long-range secondary particles. Lateral dose distributions are improved using active beam delivery methods, instead of flat fields. CONCLUSIONS: Dose-volume histograms for different treatment scenarios show that antiprotons have the potential to reduce the volume of normal tissue receiving medium to high dose, however, in the low dose region antiprotons are inferior to both protons and carbon ions. This limits the potential usage to situations where dose to normal tissue must be reduced as much as possible. PMID- 20304513 TI - Is (18)F-FDG a surrogate tracer to measure tumor hypoxia? Comparison with the hypoxic tracer (14)C-EF3 in animal tumor models. AB - INTRODUCTION: Fluorodeoxyglucose (FDG) has been reported as a surrogate tracer to measure tumor hypoxia with positron emission tomography (PET). The hypothesis is that there is an increased uptake of FDG under hypoxic conditions secondary to enhanced glycolysis, compensating the hypoxia-induced loss of cellular energy production. Several studies have already addressed this issue, some with conflicting results. This study aimed to compare the tracers (14)C-EF3 and (18)F FDG to detect hypoxia in mouse tumor models. MATERIALS AND METHODS: C3H, tumor bearing mice (FSAII and SCCVII tumors) were injected iv with (14)C-EF3, and 1h later with (18)F-FDG. Using a specifically designed immobilization device with fiducial markers, PET (Mosaic(r), Philips) images were acquired 1h after the FDG injection. After imaging, the device containing mouse was frozen, transversally sliced and imaged with autoradiography (AR) (FLA-5100, Fujifilm) to obtain high resolution images of the (18)F-FDG distribution within the tumor area. After a 48 h delay allowing for (18)F decay a second AR was performed to image (14)C-EF3 distribution. AR images were aligned to reconstruct the full 3D tumor volume, and were compared with the PET images. Image segmentation with threshold-based methods was applied on both AR and PET images to derive various tracer activity volumes. The matching index DSI (dice similarity index) was then computed. The comparison was performed under normoxic (ambient air, FSAII: n=4, SCCVII, n=5) and under hypoxic conditions (10% O(2) breathing, SCCVII: n=4). RESULTS: On AR, under both ambient air and hypoxic conditions, there was a decreasing similarity between (14)C-EF3 and FDG with higher activity sub-volumes. Under normoxic conditions, when comparing the 10% of tumor voxels with the highest (18)F-FDG or (14)C-EF3 activity, a DSI of 0.24 and 0.20 was found for FSAII and SCCVII, respectively. Under hypoxic conditions, a DSI of 0.36 was observed for SCCVII tumors. When comparing the (14)C-EF3 distribution in AR with the corresponding (18)F-FDG-PET images, the DSI reached values of 0.26, 0.22 and 0.21 for FSAII and SCCVII under normoxia and SCCVII under hypoxia, respectively. CONCLUSION: This study showed that FDG is not a good surrogate tracer for tumor hypoxia under either ambient or hypoxic conditions. Only specific hypoxia tracers should be used to measure tumor hypoxia. PMID- 20304514 TI - High-dose radiotherapy exposure to cardiac pacemakers may be safe in selected patients. PMID- 20304515 TI - Response preparation with static and moving hands: differential effects of unimanual and bimanual movements. AB - This study investigated the effects of uni- and bimanual hand movements on the efficiency of within- and between-hands response preparation in a spatial cuing task. Predictions were derived from the Grouping Model of finger preparation, inspired by insights from neurophysiology (i.e., the concepts of transcollosal facilitation and cognitive overruling of basic neural coordination patterns). Sixteen participants performed the finger cuing task with one, two, or no hand(s) moving. Reaction time results revealed that unimanual and bimanual hand movements had similar effects on within-hand preparation but differential effects on between-hands preparation. This finding demonstrates a strong dissociation between within- and across-hands finger preparation, suggesting distinct underlying mechanisms as hypothesized by the Grouping Model. PMID- 20304516 TI - Running on uneven ground: leg adjustments by muscle pre-activation control. AB - In locomotion, humans have to deal with irregularities of the ground, i.e., pathways covered with stones, grass, or roots. When they encounter ground with changes in terrain height they seem to use spring-mass dynamics to help passively stabilize their locomotory trajectory. With increasing step heights humans reduce their leg stiffness, but it is as of yet unclear whether these leg adjustments are purely passively achieved or actively in a feed-forward manner. For this, we investigated the stiffness regulation in the ankle and knee joint and analyzed the correlation between EMG, kinematic, and dynamic parameters. Nine healthy participants were running along a 17m runway with a force plate of adjustable height (steps of 0, +5, +10, and +15cm). Whole body kinematics was monitored along with surface electromyography of three selected bilateral lower limb muscles. We found that the stiffness of the ankle joint is adjusted to the vertical height of a step, in a manner similar to global leg stiffness. Furthermore, the integrated 100ms pre-activation of the m. gastrocnemius medialis (GM) depends on the vertical height of a step and correlates highly significantly with the activation of the GM but also with kinematics and dynamics. Consequently, we identified the pre-activation control as a key for altering the leg posture in preparation for altered ground properties (e.g., the height of a step or an obstacle). During the stance phase the control of activation plays a minor role since geometry and the initial conditions (e.g., leg length, landing angle, and landing velocity) ensure an adequate adjustment of joint stiffness as well as leg stiffness. PMID- 20304517 TI - Mechanisms for visuomotor adaptation to left-right reversed vision. AB - Behavioral studies suggest that the adaptation of planar arm movements to rotated visual feedback is achieved by the interplay of a gradual process which slowly rotates participants' responses by up to +/-90 degrees , and a discrete process which changes the responses by means of axis inversion. The processes for adaptation to left-right reversed visual feedback are far less well understood. To clarify this issue, 12 healthy participants performed pointing movements to targets presented in eight different directions, before and during exposure to left-right reversed visual feedback. We quantified the direction of each response 150ms after movement onset and analyzed the time-course of those directions throughout the adaptation phase, separately for different targets. For targets along the axis of inversion, we only found an increase of response variability, for targets perpendicular to that axis, we observed a discrete 180 degrees change of response direction, and for diagonal targets, we found a discrete 180 degrees change followed by a gradual "backward" shift of 90 degrees . The present findings confirm that sensorimotor adaptation is based on discrete and gradual processes, that both types of processes can occur concurrently, and suggests that those processes can contribute to adaptation in a target-specific fashion. PMID- 20304518 TI - Reduction of hexavalent chromium by carboxymethyl cellulose-stabilized zero valent iron nanoparticles. AB - The reduction of hexavalent chromium or Cr(VI) by zero-valent iron (Fe(0)) nanoparticles has received increasing attention in recent years. However, Fe(0) nanoparticles prepared using conventional methods suffered several drawbacks due to their high reactivity towards surrounding media, which led to the formation of much larger flocs and significant loss in reactivity. To overcome these problems, we synthesized Fe(0) nanoparticles by applying water-soluble carboxymethyl cellulose (CMC) as a stabilizer. CMC-stabilized Fe(0) nanoparticles displayed much less agglomeration but greater Cr(VI) reduced power than those prepared without a stabilizer. At a dose of 0.15 g L(-)(1), CMC-stabilized Fe(0) nanoparticles were able to reduce 100% of 10 mg L(-)(1) Cr(VI) in minutes. Several factors that may affect the efficiency of Cr(VI) removal were investigated. These included the concentration of CMC, the concentration of Fe(0) nanoparticles, the initial Cr(VI) concentration, the pH value, the reaction temperature and the concentration of the calcium cation in the reaction mixture. Our study suggested that the introduction of an innocuous stabilizer such as CMC could significantly improve the performance of Fe(0) nanoparticles for environmental remediation applications. PMID- 20304519 TI - [Papillary retinal nerve fiber layer thickness measurement using optical coherence tomography in children with ocular hypertension and juvenile glaucoma]. AB - PURPOSE: To compare retinal nerve fiber layer (RNFL) measurements taken with OCT in normal, ocular hypertensive, and glaucomatous eyes of children 4-18 years old. MATERIALS AND METHODS: The study included 181 eyes: 106 normal, 37 with ocular hypertension, and 38 with juvenile glaucoma. Diagnostic groups were classified based on intraocular pressure, optic nerve head appearance, visual field examination, and central corneal thickness measurement. RNFL measurements were taken using the Zeiss Stratus OCT. RESULTS: The RNLF average thickness was 94.2 + or -13.2 microm in glaucomatous eyes, 105.4 + or - 6.8 microm in ocular hypertensive eyes, and 104.8 + or - 10.3 microm in normal eyes. RNFL average thickness, inferior thickness, and superior thickness showed statistically significant differences between normal and glaucomatous eyes (p<0.01) and between glaucomatous [corrected] and ocular hypertensive eyes (p<0.01). There was no difference found between normal and ocular hypertensive eye. CONCLUSION: OCT has already shown its diagnostic efficiency in adult glaucoma. This study shows that OCT is useful in childhood glaucoma diagnosis, helping to differentiate between ocular hypertension and beginning juvenile glaucoma. PMID- 20304520 TI - [Adherence to glaucoma therapy]. AB - Adherence to glaucoma therapy is a major factor of therapeutic efficacy. It reflects the patient's perception of the glaucoma disease and its treatment. Evaluation of adherence, often underestimated, is simple with a four-step strategy underscoring the importance of informing and educating the patient. The quality of the physician-patient relationship is essential for a good adapted assessment with every patient and at all stages of the disease so as to enhance adherence to glaucoma treatment and help patients. PMID- 20304521 TI - [Treatment of glaucoma in patients with dry eye syndrome]. AB - The treatments of glaucoma or ocular hypertension are associated with numerous ocular surface changes. Similarly, these ocular surface modifications directly impact the effectiveness of these therapies. The management of patients with glaucoma or ocular hypertension also suffering from dry eye syndrome needs to reduce eye drop-induced toxicity as well as a specific treatment for the ocular surface. PMID- 20304522 TI - Oral mucous squamous cell carcinoma-an anticipated consequence of autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED). AB - Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is a rare autosomal recessive disease caused by mutations in the AIRE gene. We report the case of a female patient with a 967-979del13 mutation in the AIRE gene. Her medical history included autoimmune hypoparathyroidism, Addison disease, and chronic mucocutaneous candidiasis. At the age of 40, she developed multiple white verrucous plaques on the oral mucosa. Histologically, the lesions appeared as moderately differentiated squamous cell carcinomas. The patient subsequently developed multiple local recurrences and therefore required repeated surgery. Notably, a higher incidence rate of oral and esophageal squamous cell carcinoma has been observed in this syndrome. However, the critical pathogenetic pathways implicated in squamous cell carcinoma development in APECED are far from being well understood. PMID- 20304523 TI - Cocaine-associated retiform purpura and neutropenia: is levamisole the culprit? PMID- 20304524 TI - Duration of norovirus excretion and the longitudinal course of viral load in norovirus-infected elderly patients. AB - To prevent dissemination of norovirus in semiclosed environments such as aged care facilities, it is important to know the period of infectivity in norovirus infected individuals. We recruited 13 elderly patients aged 60-98 years with norovirus gastroenteritis (11 residents in aged-care facilities and two healthy adults) for this study, and measured the viral loads for norovirus in a total of 63 follow-up faecal samples using a real-time quantitative polymerase chain reaction assay. The average period of norovirus excretion was 14.3 days (range: 9 32 days; median: 13 days). All of the follow-up samples collected between 7 and 10 days after the onset of symptoms tested positive. Viral loads in samples collected between 14 and 18 days after the onset of symptoms were divided into three groups: those testing negative, those with <10(4) copies/g stool, and those with >10(4) copies/g stool. Stools from the group with <10(4) copies/g stool were found to be negative for norovirus up to 21-24 days after the onset of symptoms; however, the group with >10(4) copies/g stool showed prolonged norovirus excretion (up to 32 days) in stools. Although the period of infectivity of excreted viruses has not yet been clarified, these results suggest that careful attention should be taken for at least 14 days after the onset of symptoms and that the measurement of viral load in stools around 16 days after onset might be a useful method for following the course of viral shedding for each patient infected with norovirus. PMID- 20304525 TI - Audit of hand hygiene at Broadmoor, a high secure psychiatric hospital. AB - Increased security measures at high secure psychiatric hospitals can complicate hand hygiene. This audit assessed the availability of appropriate hand hygiene equipment and the practice of good hand hygiene at Broadmoor Hospital using the local hand hygiene policy as the standard for comparison. A data collection tool used to audit the hand hygiene equipment on 23 wards in the hospital showed that there were significant deficits in the supply of hand hygiene equipment on the wards. In addition, a staff survey was conducted using a questionnaire designed to assess awareness, training and hand decontamination practice among nursing staff. This survey identified a need to increase awareness of the hand hygiene policy and the appropriate timing of hand decontamination procedures. As a result of the audit, appropriate equipment was ordered and the duties of infection prevention link nurses on each ward were made more explicit; namely, to check and order equipment for hand hygiene as necessary, to conduct regular reminder sessions of the hand decontamination procedure and to raise awareness of hand hygiene policy. Posters were also placed on wards in patient areas to increase awareness of hand hygiene among patients, and alcohol gel dispensers were introduced into nursing stations. Similar audits may prove beneficial at other psychiatric hospitals. PMID- 20304526 TI - [Family doctor. A classic title]. PMID- 20304527 TI - [Crisis in family medicine: A bioethical perspective from the routine practice]. AB - From the beginning, family medicine (FM) has brought health care nearer to the population. A crisis in FM is a good time to look at the social expectations and to reformulate and to strengthen the principles that guide the specialty. An ethical reflection is presented on what to do from the microcosm of daily practice. Bureaucracy and trivialities cause a moral decline which prevents FM from offering the specific service that it should. Its visualisation as doorman to the system, a mere filter of banalities, an administration area or as a handkerchief for the system to cry on, draws a socially unacceptable caricature. It is vital for FM to reach an effective compromise preferably directed at the most vulnerable groups or individuals. But it also urgently needs a sense of recovery as an area of human promotion, in which the professionals do not lose their moral capacity to have something to desire, want, achieve and enjoy. PMID- 20304528 TI - [An evaluation of the quality of health web pages using a validated questionnaire]. AB - OBJECTIVE: The objective of the present study was to evaluate the quality of general health information in Spanish language web pages, and the official Regional Services web pages from the different Autonomous Regions. DESIGN: It is a cross-sectional study. We have used a previously validated questionnaire to study the present state of the health information on Internet for a lay-user point of view. PARTICIPANTS AND INTERVENTIONS: By mean of PageRank (Google(r)), we obtained a group of webs, including a total of 65 health web pages. We applied some exclusion criteria, and finally obtained a total of 36 webs. We also analyzed the official web pages from the different Health Services in Spain (19 webs), making a total of 54 health web pages. RESULTS: In the light of our data, we observed that, the quality of the general information health web pages was generally rather low, especially regarding the information quality. Not one page reached the maximum score (19 points). The mean score of the web pages was of 9.8+/-2.8. CONCLUSIONS: In conclusion, to avoid the problems arising from the lack of quality, health professionals should design advertising campaigns and other media to teach the lay-user how to evaluate the information quality. PMID- 20304529 TI - [Development and validation of a generic questionnaire for evaluating satisfaction in patients with chronic disease: the SAT-Q Questionnaire]. AB - OBJECTIVES: To develop and validate a brief general questionnaire to assess satisfaction in patients with chronic disease. DESIGN: epidemiological, observational, multicentre cross-sectional study. LOCATION: 4 Primary Health Care Centers from the IV Health Area in the Principality of Asturias. SUBJECTS: A total of 202 patients diagnosed with chronic illness who were following a pharmacological regimen for at least one year. METHODS: An extensive literature review was conducted to create an initial item pool of 61 questions regarding patient satisfaction. Then, a forward-backward translation into Spanish was carried out. Next, both the expert (n=8) and patient (n=30) panels led to a new version of 34 items (concerning satisfaction with medication and satisfaction with health service). Finally, scale item reduction (item-total correlation and exploratory factorial analysis -EFA-) and psychometrical validation (feasibility, reliability and criterion validity) of the SAT-Q- were evaluated. Both the SAT-Q and the SF-12 (to assess patient health related quality of life) were applied. RESULTS: Item reduction analysis resulted in 18 items: general satisfaction with medication (3), adverse-events (3), oversights (2), effectiveness (3), convenience (4) and Health services (3). Internal consistency (Cronbach alpha) and Intraclass Correlation Coefficients were moderate-high. Moreover, significant positive correlations between SAT-Q scores and SF-12 Physical and Mental Summary Components were found (with the exception of oversights). CONCLUSIONS: A brief questionnaire for measuring satisfaction in chronic patients has been developed and preliminary validated. PMID- 20304530 TI - [Non-compliance of dyslipaemic patients with electronic prescriptions]. PMID- 20304531 TI - [Analysis of the effects of pharmacotherapeutic follow-up in hypothyroid patients seen in community pharmacy]. PMID- 20304532 TI - [Acceptance of the HPV vaccination by parents of 10-year old primary schoolgirls. One year later]. PMID- 20304533 TI - [Living will declarations: Qualitative study of the elderly and primary care general practitioners]. AB - OBJECTIVES: First, to assess knowledge and attitudes of people aged 65 and over to the Advance Directives Document (ADD) and know the role that, in their opinion, a family doctor should play in the early planning of death. Second, to assess the level of knowledge and attitude of primary care physicians to that document, as well as to know the role played by these professionals. DESIGN: Qualitative, using discussion groups. Between March and May 2009 4 groups, 2 of physicians and 2 of older people, were formed. SETTING: Castile-La Mancha Primary Care Setting, Albacete and Guadalajara health areas. SUBJECTS: 15 people in the groups formed by older people and 13 in the groups of doctors. METHOD: The Krueger recommendations (1991) were followed both for the selection of subjects, conducting of the discussion groups and analysis of data. RESULTS: Doctors and patients have a positive attitude towards the ADD, but lack sufficient information to make more widespread use of it. Ignorance makes it impossible for patients to get information about the document and the lack of time makes it difficult for physicians to raise the issue in the consultation. CONCLUSIONS: Neither physicians nor the elderly have enough information regarding ADD, allowing us to recommend carrying out information campaigns and/or specific educational activities. According to physicians, alternatives to primary care consultations should be sought for patients to be informed. PMID- 20304534 TI - [Evaluation and improvement in the prescribing of anti-platelet drugs in diabetic patients]. PMID- 20304535 TI - Synthesis and antiproliferative activity of indolizine derivatives incorporating a cyclopropylcarbonyl group against Hep-G2 cancer cell line. AB - Indolizine and annulated indolizine derivatives incorporating a cyclopropylcarbonyl group were synthesized in a one pot procedure by the tanden reactions of [3+2] cycloaddition of the corresponding N-ylide with electron deficient alkene. Seventeen indolizine derivatives were reported for the first time. All the compounds were examined for their antiproliferative activity against the human hepatocellular liver carcinoma (Hep-G2) cell line by MTT method. Among the compounds tested, 5a, 5d, 5 g and 5 j showed the most favorable activities with IC(50) values of 0.39, 0.48, 0.29 and 0.20 microg/mL. Especially, compound 5 j displayed potent antiproliferative activities with IC(50) value of 0.20 microg/mL, and showed significant EGFR kinase inhibitory activity with IC(50) value of 0.085 microM. Docking simulations of 5 j were carried out to illustrate the binding mode of the molecular into the EGFR active site. PMID- 20304536 TI - Design, synthesis and 3D-QSAR of beta-carboline derivatives as potent antitumor agents. AB - In a continuing effort to develop novel beta-carbolines endowed with better pharmacological profiles, a series of beta-carboline derivatives were designed and synthesized based on the previously developed SARs. Cytotoxicities in vitro of these compounds against a panel of human tumor cell lines were also investigated. The results demonstrated that the N2-benzylated beta-carbolinium bromides 56-60 represented the most potent compounds with IC50 values lower than 10 microM. The application of 3D-QSAR to these compounds explored the structural basis for their biological activities. CoMFA (q2=0.513, r2=0.862) and CoMSIA (q2=0.503, r2=0.831) models were developed for a set of 47 beta-carbolines. The results indicated that the antitumor pharmacophore of these molecules were marked at position-1, -2, -3, -7 and -9 of beta-carboline ring. PMID- 20304537 TI - Synthesis and preliminary biological evaluation of novel taspine derivatives as anticancer agents. AB - Antiangiogenic therapy might represent a new promising anticancer therapeutic strategy. Taspine can significantly inhibit cell proliferation of human umbilical vein endothelial cells (HUVECs) induced by vascular endothelial growth factor 165, which is crucial for angiogenesis. In this study, a series of novel taspine derivatives were synthesized and screened for in vitro anticancer and antiangiogenesis activities. The majority of the derivatives demonstrated a moderate degree of cytotoxicity against human cancer cell lines. One of them (14) exhibited much better antiproliferative activity against CACO-2 (IC(50)=52.5microM) and ECV304 (IC(50)=2.67microM) cells than taspine did. Some of them were also effective in antiproliferative assays against HUVECs. The in silico estimate of solubility of title compounds were higher than that of taspine. PMID- 20304538 TI - Trifluoromethyl-promoted homocamptothecins: synthesis and biological activity. AB - The homocamptothecin (hCPT) represents a new class of topoisomerase inhibitor which combines enhanced plasma stability and strong antitumor activity. Fluorine imparts desirable characteristics to drugs by modulating both the pharmacokinetics and pharmacodynamic properties of a drug. Therefore, in an attempt to improve the antitumor activity of homocamptothecins, seven new 7 trifluoromethylated homocamptothecin derivatives were prepared by proline catalyzed Friedlander annulation. The antitumor activity in vitro and in vivo on cancer cell lines, and inhibitory properties of topoisomerase I-mediated DNA cleavage of compounds 6c and 8b were evaluated. Several of these trifluoromethylated hCPT derivatives (such as 6a, 6b and 6c) possessed higher in vitro antitumor activity than topotecan (TPT). Especially, the compound 6c showed effective in vivo antitumor activity comparable to that of TPT. PMID- 20304540 TI - n-3 LC-PUFA-enriched dairy products are able to reduce cardiovascular risk factors: a double-blind, cross-over study. AB - BACKGROUND: & AIMS: The effects of n-3 LC-PUFA-supplemented dairy products on cardiovascular risk factors in mildly hypertriacylglycerolemic patients (TAG: >=1.5 mmol/L) were determined. METHODS: Fifty-one patients (25 f, 26 m) were included in the double-blind, placebo-controlled cross-over study and were randomly divided into two groups. Both groups received intervention (3g n-3 LC PUFA/d) and control dairy products consecutively for fifteen weeks with a ten week wash-out phase between the two treatments. Blood samples and 24-h urine were obtained at the beginning and at the end of each period. The blood lipids were determined by enzymatic methods and using the autoanalyser Synchron LX systems (Beckman Coulter). 7,8-Dihydro-8-oxo-2'-deoxyguanosine and fatty acids were analysed with HPLC and GC. RESULTS: Generally, the consumption of the intervention products resulted in a significant improvement of cardiovascular risk factors, e.g., n-3 FA index, AA/EPA ratio, total cholesterol, and TAG. The TAG and LDL/HDL ratio were lower at the end of the intervention period in comparison with the control period, whereas HDL cholesterol was higher at the end of the intervention period. Further, n-3 LC-PUFA-enriched products did not cause additional oxidative DNA damage as shown by the 7,8-dihydro-8-oxo-2' deoxyguanosine excretion. CONCLUSIONS: The consumption of n-3 LC-PUFA supplemented dairy products decreases cardiovascular risk factors. PMID- 20304539 TI - Nursing and midwife students' willingness to provide care to patients with HIV/AIDS--a comparative study in Finland, Estonia and Lithuania. AB - This article presents results on nursing and midwife students' willingness to care for patients with human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS). An international cross-sectional survey design was used and the data were collected from educational institutions in Finland (N=169), Estonia (N=132) and Lithuania (N=170) between autumn 2005 and spring 2006. Participants (N=471) were nursing and midwife students training to be RN, public health nurses or midwives. A modified version of a scale developed by Duppert et al. (1994) was applied to measure willingness to care for patients with HIV/AIDS. The study found a general willingness on the part of students to provide care for patients with HIV/AIDS. However, nursing and midwife students willingness varied between countries and was also related to specific nursing interventions. Factors associated with students willingness also varied within each country, depending on nurses' age, nursing experience (Finland), positive attitudes to treating patients with HIV/AIDS in general (Finland, Estonia), and previous experience in taking care of a patient with HIV/AIDS (Lithuania). It is important to develop strategies for nursing vulnerable patient populations and international nursing curricula to identify prejudicial thinking and intolerance towards patients with HIV/AIDS. PMID- 20304541 TI - Use of the alar base cinch suture in Le Fort I osteotomy: is it effective? AB - The alar base cinch suture is often used to mitigate the unfavourable increase in nasal width after Le Fort I impaction or advancement of the maxilla. Recently a number of studies have looked at the stability and clinical outcome of this intervention. We investigated the effect of an alar base cinch suture on the change in width of the alar base after Le Fort I osteotomy using a three dimensional imaging system. Twenty-eight patients were prospectively randomised into an intervention group where a cinch suture was used, and a control group. The width of the alar base was measured before operation, and then at one, and six months. At six months it had increased from baseline by a median of 2mm in all patients. The median increase was greater in the control group than in the cinch placement group, but the difference was small. The range in both groups was large, indicating great individual variability. There was an overall reduction in the width of the alar base between one and six months after operation, which indicated some resolution of soft tissue oedema associated with the operation, but the median reduction was small and unlikely to be clinically significant. The preliminary findings suggest that the suture confers little benefit in controlling the width of the alar base of the nose after Le Fort I osteotomy. More recently it has been suggested that procedures using a modified cinch suture may result in greater stability. PMID- 20304542 TI - The role of therapist training in the implementation of psychosocial treatments: a review and critique with recommendations. AB - Evidence-based treatments (EBT) are underutilized in community settings, where consumers are often seen for treatment. Underutilization of EBTs may be related to a lack of empirically informed and supported training strategies. The goals of this review are to understand the state of the literature for training therapists in psychotherapy skills and to offer recommendations to improve research in this area. Results of this review of 55 studies evaluating six training methods indicate that multi-component trainings have been studied most often and have most consistently demonstrated positive training outcomes relative to other training methods. Studies evaluating utility of reading, self-directed trainings, and workshops have documented that these methods do not routinely produce positive outcomes. Workshop follow-ups help to sustain outcomes. Little is known about the impact of train-the-trainer methods. Methodological flaws and factors that may influence training outcome and future directions are also reviewed. PMID- 20304543 TI - Efficacy of temporomandibular joint ankylosis surgical treatment. AB - PURPOSE: The purpose of the present study was to answer the following clinical question: of the patients with temporomandibular joint ankylosis, do those treated with ankylosis resection and ramus-condyle unit reconstruction with a prosthetic total joint (total joint replacement [TJR]) have improved jaw function and decreased pain compared with those treated with ankylosis resection and interpositional arthroplasty (IA)? MATERIALS AND METHODS: Using a retrospective study design, the investigators enrolled a sample derived from the population of patients presenting to the Massachusetts General Hospital (Boston, MA) and the University of Oslo Faculty of Dentistry from 1998 to 2008 for the evaluation and management of temporomandibular joint ankylosis. The primary predictor variable was treatment (ie, TJR or IA). The outcome variables were the maximal interincisal opening and pain. Data analyses were performed using bivariate and multiple regression methods. RESULTS: The final study sample included 36 subjects with a mean age of 40 +/- 13.1 years, and 25 were women (69%). Of the 36 patients, 14 (39%) and 22 (61%) were in the TJR and IA groups, respectively. The changes in the maximal interincisal opening in the TJR and IA groups were 9.4 +/- 6.7 and 18 +/- 9.7 mm (P = .02). After adjusting for institutional location, number of previous operations, laterality (unilateral versus bilateral operation), age, and etiology, the difference in the maximal interincisal opening between the 2 treatment groups was not significant (P = .06). The changes between preoperative and postoperative pain scores were insignificant between the groups (P = .16). CONCLUSION: Ankylosis resection and ramus-condyle unit reconstruction with a prosthetic total joint and IA produced comparable outcomes in terms of mandibular range of motion and pain. PMID- 20304544 TI - Retrospective review of 99 patients with secondary alveolar cleft repair. AB - PURPOSE: The purpose of the present review was to evaluate the protocol and technique used in a large population of patients with cleft lip and palate when secondary grafting is performed during the early mixed dentition stage, as determined by eruption of the central incisor. In the United States, most investigators have recommended alveolar grafting at the 9- to 11-year age range or before eruption of the permanent canines. MATERIALS AND METHODS: An institutional review board-approved chart review of 99 patients undergoing alveolar cleft bone grafting during a 7-year period at a single institution was performed. Data were collected regarding demographics, operative time, length of hospitalization, follow-up time, complications, and additional procedures performed. The cases were divided by patient age into 2 groups: group 1, aged 6 to 8 years (n = 61); and group 2, aged 9 years and older (n = 38). Statistical analysis was performed for various comparisons in the study. RESULTS: The average operative time for groups 1 and 2 was 86 and 103 minutes, respectively. The complication rate, length of stay, and follow-up time between the 2 groups was not statistically significant at the P = .05 significance level. CONCLUSIONS: We recommend earlier bone grafting at or before the eruption of the central incisor, rather than delaying until the cuspid tooth root is 25% formed. We believe this will provide better bone support for the dentition, a decreased burden of treatment for the patient, and improved quality of life. Performing the procedure at this time can lead to decreased operative times, with comparable postoperative outcomes. PMID- 20304545 TI - [Validation of the Spanish version of the Revised Cystic Fibrosis Quality of Life Questionnaire in adolescents and adults (CFQR 14+ Spain)]. AB - BACKGROUND: The aim of this study was to assess the validity and reliability of the Spanish version of the revised disease-specific health related quality of life questionnaire for adolescents and adults with cystic fibrosis (CFQR 14+ Spain). METHODS: A total of 43 cystic fibrosis (CF) patients completed the CFQR 14+ Spain. Forced expiratory volume in 1 second, in percentage of predicted - FEV(1) (%)-, number of respiratory exacerbations, 6-minute walk test, Bhalla score (based on computerized tomography of the chest), fat-free mass index, body mass index (BMI), faecal fat and St George's Respiratory Questionnaire were included as measurements of health status. RESULTS: Ten out of the twelve scales had alpha coefficients above 0.70. Test-retest correlations (Spearman) ranged from 0.49 to 0.95 and they were significant in all scales. Intraclass correlations ranged from 0.47 to 0.95 (ten out of the twelve scales were >0.70) forty out of the fifty items have correlations between items and scale above 0.70. All the CFQR+14 scales, except the digestive symptoms scale, discriminated significantly between patients with mild, moderate and severe disease (according to FEV(1) (%)). Other respiratory parameters also discriminated significantly between patients with mild-moderate and severe disease. Only some scales discriminated significantly between nourished and malnourished patients. All of the scales met standards for floor effects (<15% of the responders with the lowest score) but not for ceiling effects (only five out of the twelve). CONCLUSION: The Spanish CFQR14+ (Spain) is a reliable and valid instrument for measuring the health-related quality of life in Spanish adolescents and adults with CF, though with the exception of a few of its subscales. PMID- 20304547 TI - Identifying non-technical skills and barriers for improvement of teamwork in cardiac arrest teams. AB - BACKGROUND: The application of non-technical skills (NTSs) in health care has previously been described in other health-care educational programmes. NTSs are behavioural principles such as leadership, task distribution and communication. The aim of this study was to identify NTSs suitable for improving team performance in multi-professional cardiac arrest teams, and to describe barriers to the use and implementation of such NTSs by using a qualitative method. METHODS: Individual semi-structured interviews were conducted with 11 Danish Advanced Life Support instructors during the period April 2006 to November 2006. Interviews were focussed on barriers and recommendations for teamwork in the cardiac arrest team, optimal policy for improvement of resuscitation training and clinical practice, use of cognitive aids and adoption of European Resuscitation Council (ERC) Guidelines 2005. Interviews and data analysis were supported by a template describing 25 NTSs derived from other educational programmes in health care. RESULTS: A framework with five categories relating to NTSs was identified: leadership, communication, mutual performance monitoring, maintenance of standards and guidelines and task management. Important barriers that were identified were inexperienced team leaders, task overload and hierarchic structure in the teams' inability to maintain focus on chest compressions. CONCLUSION: Interview participants pointed out that NTSs of teams could improve the treatment of cardiac arrest, but several barriers to this exist. Improving resuscitation training should include considerations regarding team leader experience, structured communication, mandatory use of cognitive aids, avoidance of task overload and mutual performance monitoring to avoid unnecessary interruptions in chest compressions. PMID- 20304548 TI - Compression range for pediatric CPR training mannequin should match physiological parameters. PMID- 20304549 TI - Immunophenotypic abnormalities of CD8+ T-cell subsets in a patient with unusual Good's Syndrome. PMID- 20304551 TI - Occurrence of endometrial cancer six years after treatment with thermal balloon ablation (Thermachoice): first case report. PMID- 20304552 TI - Validity and legacy of prostate-specific antigen (PSA) and PSA-based parameters and isoforms in the new millennium. PMID- 20304553 TI - Resveratrol induces DNA double-strand breaks through human topoisomerase II interaction. AB - Resveratrol, a stilbene found in grapes and wine, is one of the most interesting natural compound due to its role exerted in cancer prevention and therapy. In particular, resveratrol is able to delay cell cycle progression and to induce apoptotic death in several cell lines. Here we report that resveratrol treatment of human glioblastoma cells induces a delay in cell cycle progression during S phase associated with an increase in histone H2AX phosphorylation. Furthermore, with an in vitro assay of topoisomerase IIalpha catalytic activity we show that resveratrol is able to inhibit the ability of recombinant human TOPO IIalpha to decatenate kDNA, so that it could be considered a TOPO II poison. PMID- 20304554 TI - Performance and thermal behavior of wood plastic composite produced by nonmetals of pulverized waste printed circuit boards. AB - A new kind of wood plastic composite (WPC) was produced by compounding nonmetals from waste printed circuit boards (PCBs), recycled high-density polyethylene (HDPE), wood flour and other additives. The blended granules were then extruded to profile WPC products by a conical counter-rotating twin-screw extruder. The results showed that the addition of nonmetals in WPC improved the flexural strength and tensile strength and reduced screw withdrawal strength. When the added content of nonmetals was 40%, the flexural strength of WPC was 23.4 MPa, tensile strength was 9.6 MPa, impact strength was 3.03 J/m(2) and screw withdrawal strength was 1755 N. Dimensional stability and fourier transform infrared spectroscopy (FTIR) of WPC panels were also investigated. Furthermore, thermogravimetric analysis showed that thermal degradation of WPC mainly included two steps. The first step was the decomposition of wood flour and nonmetals from 260 to 380 degrees C, and the second step was the decomposition of HDPE from 440 to 500 degrees C. The performance and thermal behavior of WPC produced by nonmetals from PCBs achieves the standard of WPC. It offers a novel method to treat nonmetals from PCBs. PMID- 20304555 TI - Bisphenol A removal by the Dracaena plant and the role of plant-associating bacteria. AB - Dracaena sanderiana and Dracaena fragrans plants, as representatives of native, tropical, evergreen plants with fibrous root systems, were evaluated for bisphenol A (BPA) tolerance and uptake capability. D. sanderiana demonstrated significantly higher BPA removal capability than D. fragrans. Therefore, it was chosen for further study. D. sanderiana tolerated BPA toxicity levels up to 80 microM, while higher BPA concentrations damaged the plant. In the sterile hydroponic system with an initial BPA concentration of 20 microM, the plant could uptake approximately 50% of the BPA. The plant's ability to translocate BPA was confirmed by the detection of BPA that accumulated at the roots and stems, but not at the leaves of the plant. Upon BPA exposure, the D. sanderiana secreted extracellular plant mucilage as a protective barrier to the toxic compound. In the non-sterile treatment, the BPA dissipation was contributed not only by the D. sanderiana plant, but also by the co-existing microbes. The BPA reached 85% of the initial concentration at 20 microM. Among the six plant-associating bacterial isolates, Bacillus cereus strain BPW4 and Enterobacter sp. strain BPW5 colonized the D. sanderiana root surface and facilitated BPA dissipation in the hydroponic treatment system. In addition, the success of the BPA treatment in the hazardous waste landfill leachate demonstrated the potential application of D. sanderiana plant in the phytoremediation of BPA contaminated wastewater or industrial leachate. PMID- 20304556 TI - Risk factors for onset of chronic oro-facial pain--results of the North Cheshire oro-facial pain prospective population study. AB - Due to the cross-sectional nature of previous studies, whether mechanical factors predict the onset of Chronic oro-facial pain remains unclear. Aims of the current study were to test the hypotheses that self-reported mechanical factors would predict onset of Chronic oro-facial pain and that any observed relationship would be independent of the confounding effects of psychosocial factors and reporting of other unexplained symptoms. About 1735 subjects who had completed a baseline questionnaire were assessed at 2year follow-up for the presence of Chronic oro facial pain, psychosocial factors (anxiety and depression, illness behaviour, life stressors and reporting of somatic symptoms), mechanical dysfunction (facial trauma, grinding, phantom bite and missing teeth) and reporting of other unexplained symptoms (chronic widespread pain, irritable bowel syndrome and chronic fatigue). About 1329 subjects returned completed questionnaires (adjusted response rate 87%). About 56 (5%) reported new episodes of Chronic oro-facial pain at follow-up. Univariate analyses showed that age, gender, reporting of other unexplained symptoms, psychosocial factors and two self-report mechanical factors predicted the onset of Chronic oro-facial pain. However multivariate analysis showed that mechanical factors did not independently predict onset. The strongest predictors were health anxiety (Relative Risk (RR) 2.8, 95% CI 1.3 6.2), chronic widespread pain (RR 4.0 95% C.I. 2.2-7.4) and age (RR 0.2, 95% CI 0.1-0.7). The findings from this prospective study support the hypothesis that psychosocial factors are markers for onset of Chronic oro-facial pain. The efficacy of early psychological management of Chronic oro-facial pain to address these factors should be a priority for future investigations. PMID- 20304557 TI - The effect of the menstrual cycle on affective modulation of pain and nociception in healthy women. AB - Research indicates pain may be influenced by the menstrual cycle. While the mechanisms underlying these effects are unclear, it is possible that menstrual phase-related changes in endogenous pain modulation contribute. The present study used well-validated methods to study affective modulation of pain and the nociceptive flexion reflex (NFR) in healthy women during two menstrual phases (mid-follicular vs. late-luteal). Women (N=41) tracked their menstrual phases for three complete cycles and were asked to attend two laboratory testing sessions in the second and third cycles to assess affective modulation of pain and nociception (testing order counterbalanced). Menstrual phase was assessed from daily diaries, luteinizing hormone tests, and basal body temperature. At each session, emotionally charged pictures were presented and suprathreshold electrocutaneous stimulations were delivered during and in between pictures. Subjective and physiological emotional reactions were recorded in response to each picture and pain ratings and NFRs were recorded in response to each suprathreshold stimulus. Results suggested pictures effectively manipulated emotion in both menstrual phases. Moreover, arousing unpleasant pictures enhanced pain and NFR, whereas arousing pleasant pictures inhibited pain and NFR. These modulatory effects were similar in both menstrual phases. Together, these findings suggest that affective engagement of corticospinal mechanisms does not differ across these phases of the menstrual cycle. However, future research is needed to directly assess the relationship between affective modulation of pain/nociception and inter- and intra-individual differences in ovarian hormones and to extend these findings to women who suffer from menstrual cycle-related pain (e.g., premenstrual dysphoric disorder, fibromyalgia). PMID- 20304558 TI - Chronic low back pain analgesic studies--a methodological minefield. PMID- 20304559 TI - Scanning probe lithography for fabrication of Ti metal nanodot arrays. AB - We report fabrication of Ti metal nanodot arrays by scanning probe microscopic indentation. A thin poly-methylmethacrylate (PMMA) layer was spin-coated on Si substrates with thickness of 70nm. Nanometer-size pore arrays were formed by indenting the PMMA layer using a cantilever of a scanning probe microscope. Protuberances with irregular boundaries appeared during the indentation process. Control of approach and pulling-out speed during indentation was able to dispose of the protrusions. Ti metal films were deposited on the patterned PMMA layers by a radio-frequency sputtering method and subsequently lifted off to obtain metal nanodot arrays. The fabricated metal nanodot arrays have 200nm of diameter and 500nm of interdistance, which corresponds to a density of 4x10(8)/cm(2). Scanning probe-based measurement of current-voltage (I-V) behaviors for a single Ti metal nanodot showed asymmetric characteristics. Applying external bias is likely to induce oxidation of Ti metal, since the conductance decreased and volume change of the dots was observed. I-V behaviors of Ti metal nanodots by conventional e beam lithography were also characterized for comparison. PMID- 20304560 TI - Tick reservoirs for piroplasms in central and northern Italy. AB - Ticks, collected in central and northern Italy from pets, livestock, wild animals and the environment (n=2107), were identified by microscopy and processed by molecular diagnostics to determine the species that act as a reservoir for piroplasms. A total of 11 ixodid tick species were identified, with five of them proving to be piroplasm positive. Molecular diagnostics identified Theileria equi and eight Babesia species in 52 adult specimens, mostly (n=50) removed from piroplasm-free vertebrate hosts. Ixodes ricinus hosted the highest number of species, although the highest infection rate was recorded in Hyalomma marginatum (9.1%), followed by I. ricinus (5.1%), Dermacentor marginatus (5%), Rhipicephalus turanicus (3.1%) and R. sanguineus (1.2%). Novel tick/pathogen associations were detected, suggesting that certain tick species (such as Hy. marginatum, R. sanguineus and I. ricinus) are vector of more piroplasm species than previously thought. Trans-stadial maintenance of the piroplasms was observed in each positive tick species; vertical transmission of B. canis canis was demonstrated in R. sanguineus. Finally, the detection of Babesia sp., B. microti-like species and B. rodhaini, phylogenetically related to zoonotic species, suggests that the human population could be at risk of infection in the studied area. PMID- 20304561 TI - The preparation of neem oil microemulsion (Azadirachta indica) and the comparison of acaricidal time between neem oil microemulsion and other formulations in vitro. AB - The preparation of neem oil microemulsion and its acaricidal activity in vitro was developed in this study. In these systems, the mixture of Tween-80 and the sodium dodecyl benzene sulfonate (SDBS) (4:1, by weight) was used as compound surfactant; the mixture of compound surfactant and hexyl alcohol (4:1, by weight) was used as emulsifier system; the mixture of neem oil, emulsifier system and water (1:3.5:5.5, by weight) was used as neem oil microemulsion. All the mixtures were stired in 800 rpm for 15 min at 40 degrees C. The acaricidal activity was measured by the speed of kill. The whole lethal time value of 10% neem oil microemulsion was 192.50 min against Sarcoptes scabiei var. cuniculi larvae in vitro. The median lethal time value was 81.7463 min with the toxicity regression equations of Y=-6.0269+3.1514X. These results demonstrated that neem oil microemulsion was effective against Sarcoptes scabie var. cuniculi larvae in vitro. PMID- 20304562 TI - Timing of adjuvant systemic therapy and radiotherapy after breast-conserving surgery and mastectomy. AB - In the last two decades, systemic adjuvant treatment for breast cancer, in association with radiotherapy, has been shown to prolong disease-free survival and overall survival in patients with operable breast tumors. So far, the optimal sequence of systemic therapy and radiotherapy for breast cancer patients after conservative surgery or mastectomy is unclear. Several retrospective analyses showed a possible detrimental effect on local regional recurrence rates when radiation therapy is delayed after chemotherapy. On the other hand, delaying chemotherapy after radiotherapy may increase the risk of distant failure and affect the survival. Concurrent administration of targeted treatment (e.g. non anthracycline/taxane containing chemotherapy, trastuzumab, endocrine therapy) with radiotherapy is considered a valid option. A "tailored" approach on sequencing of chemotherapy and radiotherapy which takes into account various variables, such as histological and biological features of the tumor, as well as the patient status and the treatment modality is required in order to optimize the delivery of adjuvant treatments. This review focuses on the effects of timing of chemotherapy-radiotherapy and risks of relapse, in terms of locoregional and distant recurrence in patients with operable breast cancer. PMID- 20304563 TI - Giving birth to a new brain: hormone exposures of pregnancy influence human memory. AB - Mammalian pregnancy produces alterations in maternal physiology that are necessary for maintaining gestation, fetal development and parturition. These changes also may prepare the maternal brain for the unique demands of motherhood. Parous rodents exhibit long-term changes in neurological structure and function and human work suggests that other landmark events in the reproductive cycle, such as menarche and menopause, influence cognition. However, the influence of pregnancy on the human brain remains to be elucidated. This study indicates that verbal recall memory (but not recognition or working memory) diminishes during human pregnancy and that these decrements persist after parturition. Further, prenatal glucocorticoids and estrogen are associated with these alterations. To meet the challenges of motherhood, the female brain may be remodeled, a process that appears to be initiated prenatally. However, it is not often that adaptation is achieved without an associated cost. For the human, in the case of the new maternal brain, diminished memory performance may reflect such a cost. PMID- 20304564 TI - Primary gastric inflammatory myofibroblastic tumor: a clinicopathologic and immunohistochemical study of 5 cases. AB - Primary gastric inflammatory myofibroblastic tumors are rare. Here we report on 5 such cases (4 males and 1 female, age range 36-45 years). Their presenting symptoms included abdominal mass (5 patients), abdominal pain (4 patients), and upper gastrointestinal hemorrhage (1 patient). Tumor size ranged from 4.5 to 8 cm in the greatest dimension. Histologically, these tumors showed three patterns: myxoid hypocellular, fascicular, and hyalinized. A lymphoplasmacytic infiltrate was present in all 5 tumors. One to two mitotic figures were recognized in 10 high power fields (HPFs) in 4 patients and focally up to 5 in 10HPFs in 1 patient. No prominent nuclear atypia or necrosis was observed. ALK, smooth muscle actin, and vimentin staining were observed in all tumors. One tumor focally expressed desmin. S-100, CD21, CD34, CD35, CD68, and CD117 were negative in all IMTs. The patients were followed up for 2-5 years (mean 3.4 years), and none of them had tumor metastasis or died. Only one patient developed local recurrence and is now alive with no evidence of disease after the second surgery (11 months after the second surgery). Our results indicate that primary gastric IMTs have an intermediate behavior as seen at other sites. PMID- 20304565 TI - Improvement in interobserver accuracy in delineation of the lumpectomy cavity using fiducial markers. AB - PURPOSE: To determine, whether the presence of gold fiducial markers would improve the inter- and intraphysician accuracy in the delineation of the surgical cavity compared with a matched group of patients who did not receive gold fiducial markers in the setting of accelerated partial-breast irradiation (APBI). METHODS AND MATERIALS: Planning CT images of 22 lumpectomy cavities were reviewed in a cohort of 22 patients; 11 patients received four to six gold fiducial markers placed at the time of surgery. Three physicians categorized the seroma cavity according to cavity visualization score criteria and delineated each of the 22 seroma cavities and the clinical target volume. Distance between centers of mass, percentage overlap, and average surface distance for all patients were assessed. RESULTS: The mean seroma volume was 36.9 cm(3) and 34.2 cm(3) for fiducial patients and non-fiducial patients, respectively (p = ns). Fiducial markers improved the mean cavity visualization score, to 3.6 +/- 1.0 from 2.5 +/- 1.3 (p < 0.05). The mean distance between centers of mass, average surface distance, and percentage overlap for the seroma and clinical target volume were significantly improved in the fiducial marker patients as compared with the non fiducial marker patients (p < 0.001). CONCLUSIONS: The placement of gold fiducial markers placed at the time of lumpectomy improves interphysician identification and delineation of the seroma cavity and clinical target volume. This has implications in radiotherapy treatment planning for accelerated partial-breast irradiation and for boost after whole-breast irradiation. PMID- 20304566 TI - Local response and impact on survival after local ablation of liver metastases from colorectal carcinoma by computed tomography-guided high-dose-rate brachytherapy. AB - PURPOSE: To determine local tumor control after CT-guided brachytherapy at various dose levels and the prognostic impact of extensive cytoreduction in colorectal liver metastases. METHODS AND MATERIALS: Seventy-three patients were treated on a single-center prospective trial that was initially designed to be randomized to three dose levels of 15 Gy, 20 Gy, or 25 Gy per lesion, delivered in a single fraction. However, because there was a high rate of cross-over of subjects from higher to lower dose levels, this study is better understood as a prospective trial with three dose levels. No upper size limit for the metastases was applied. We assessed time to local progression, progression-free survival, and overall survival. RESULTS: According to safety constraints cross-over was performed. The final assignment was n = 98, n = 68, and n = 33 in the 15-Gy, 20 Gy, and 25-Gy groups, respectively. Median diameter of the largest tumor lesion in each patient was 5 cm (range, 1-13.5 cm). Estimated mean local recurrence-free survival for all lesions was 34 months (median not reached). The group assigned to 15 Gy after cross-over displayed 34 local recurrences out of 98 lesions; 20 Gy, 15 out of 68 lesions; 25 Gy, 1 out of 33 lesions. The difference between the 25-Gy and the 20-Gy or 15-Gy group was significant (p < 0.05). Repeated local tumor ablations were the most prominent factor for increased survival and dominated additional systemic antitumor treatments. CONCLUSIONS: Local tumor control after CT-guided brachytherapy of colorectal liver metastases demonstrated a strong dose dependency. The role of extensive minimally invasive tumor ablation in metastatic colorectal cancer needs to be further established. PMID- 20304567 TI - Cholesterol-loaded cyclodextrin enhances osmotic tolerance and inhibits the acrosome reaction in rabbit spermatozoa. AB - The effects of cholesterol-loaded cyclodextrin (CLC) treatment on the osmotic tolerance and ability to undergo the acrosome reaction of rabbit spermatozoa, with an unusually high cholesterol/phospholipid ratio in plasma membranes, were examined in two successive experiments. In the first experiment, CLC-pretreated and untreated sperm cells were exposed for 15min to one of five fructose solutions, adjusted to 20, 80, 290, 500 or 1500mOsm/L. After the anisoosmotic challenge, the integrity of sperm membranes in the CLC-supplemented (at a dose level of 3mg/120x10(6)spermatozoa) and control groups was estimated by a modified hypoosmotic swelling test (HOST) associated with a supravital eosin staining test (HE-test). In the second part of the study, the influence of cholesterol supplementation on the acrosome reaction of sperm cells stimulated by either calcium ionophore A23187 (CI) or lysophosphatidylcholine (LPC) was evaluated. CLC pretreatment increased viable and live-HOST-responsive sperm rates (P<0.01) after incubation in anisoosmotic solutions varying from 80 to 1500mOsm/L. However, CLC supplementation did not influence the percentage of HOST-responsive sperm cells (P>0.05). A significant interaction was determined between CLC pretreatment and the level of osmotic pressure in maintaining the functional and physical integrities of sperm membranes undergoing osmotic challenges. Both CI and LPC successfully induced the acrosome reaction in rabbit spermatozoa (P<0.001). Compared with CI, LPC was more effective (P<0.0001). CLC pretreatment resulted in a significant reduction (P<0.01) in the percentage of acrosome reacted sperm cells irrespective of the inducing agent, either CI or LPC. In conclusion, CLC treatment enhanced the anisoosmotic tolerance of rabbit spermatozoa and reduced their ability to undergo the acrosome reaction after stimulation by CI or LPC. PMID- 20304568 TI - Levels of selected T lymphocyte subpopulations in peripheral blood of mares which experienced early embryonic death. AB - The objective of the present study was to analyse the immune status of mares in the early stages of pregnancy and mares which experienced early embryonic death (EED). Forty-eight fertile purebred Arabian mares were used for the study. The mares were divided into two groups. Group I was the control group composed of 32 mares in the early stages of a normal pregnancy. Group II was composed of 12 mares which had experienced EED. In both groups, subpopulations of T lymphocytes containing CD2(+), CD4(+) and CD8(+) were characterized using flow cytometry. The percentages of CD3(+) lymphocytes (adding up the cells with CD4(+) and CD8(+) phenotypes) and of NK cells (subtracting CD3(+) cells from CD2(+) lymphocytes) calculated. Due to its suppressive effects on T lymphocytes during pregnancy, TGF beta1 was determined using ELISA. The findings revealed that in mares with EED, the percentages of lymphocytes TCD2(+), TCD4(+), NK cells at EED, i.e. between days 14 and 21, were significantly higher compared to mares without EED. The changes in the CD4(+)/CD8(+) ratio were similar. In the EED group, this ratio significantly increased between the 96th hour and the 30th day after ovulation compared to mares without EED. Otherwise, serum levels of TGF-beta1 in the EED group were significantly lower than in the control group. The results show that mares which experienced an EED develop inflammatory reactions which activate Th1 cell immune responses. PMID- 20304569 TI - Evidence-based survey of the elimination rates of ethanol from blood with applications in forensic casework. AB - Reliable information about the elimination rate of alcohol (ethanol) from blood is often needed in forensic science and legal medicine when alcohol-related crimes, such as drunken driving or drug-related sexual assault are investigated. A blood sample for forensic analysis might not be taken until several hours after an offence was committed. The courts usually want to know the suspect's blood alcohol concentration (BAC) at some earlier time, such as the time of driving. Making these back calculations or retrograde extrapolations of BAC in criminal cases has many proponents and critics. Ethanol is eliminated from the body mainly by oxidative metabolism in the liver by Class I isoenzymes of alcohol dehydrogenase (ADH). Ethanol is an example of a drug for which the Michaelis Menten pharmacokinetic model applies and the Michaelis constant (k(m)) for Class I ADH is at a BAC of 2-10mg/100mL. This means that the enzyme is saturated with substrate after the first few drinks and that zero-order kinetics is adequate to describe the declining phase of the BAC profile in most forensic situations (BAC>20mg/100mL). After drinking on an empty stomach, the elimination rate of ethanol from blood falls within the range 10-15 mg/100mL/h. In non-fasted subjects the rate of elimination tends to be in the range 15-20mg/100mL/h. In alcoholics during detoxification, because activity of microsomal enzyme (CYP2E1) is boosted, the ethanol elimination rate might be 25-35 mg/100mL/h. The slope of the BAC declining phase is slightly steeper in women compared with men, which seems to be related to gender differences in liver weight in relation to lean body mass. The present evidence-based review suggests that the physiological range of ethanol elimination rates from blood is from 10 to 35 mg/100mL/h. In moderate drinkers 15 mg/100mL/h remains a good average value for the population, whereas in apprehended drivers 19 mg/100mL/h is more appropriate, since many of these individuals are binge drinkers or alcoholics. In preparing this article, a large number of peer-reviewed publications were scrutinized. Only those meeting certain standards in experimental design, dose of alcohol and blood-sampling protocol were used. The results presented can hopefully serve as best-practice guidelines when questions arise in criminal and civil litigation about the elimination rate of ethanol from blood in humans. PMID- 20304570 TI - Forensic dental identification. AB - Identification of deceased persons is the most common role of the forensic dentist. Forensic physical comparison of antemortem and postmortem dental data is used to establish that a found body and a missing person are one and the same to a high degree of certainty. An overview of this role is presented as a review of dental identification. PMID- 20304571 TI - Interpreting group differences using Demirjian's dental maturity method. AB - Although Demirjian's method is designed to assess dental maturity at the individual level, significant differences between average dental age and real age for groups have been interpreted as population differences. The aim of this study was to describe the variation in maturity score for age and age for maturity score from a large collaborative database of children and discuss methods adapted for groups in light of this. Tooth stages from radiographs of 4710 males and 4661 females (age 2-18) were used and dental maturity scores calculated using Demirjian and Goldstein. The mean, standard deviation, standard error and 95% confidence intervals of maturity score by age group (6 and 12 months groups) and age by maturity score (5 points) groups were calculated. Adapted maturity curves from 13 published studies of boys from Europe, Middle East, Africa, India, China and South America were compared to the database. Most adapted curves at the 50th percentile from world regions fell within the 95% confidence intervals. Those that did not, were hampered by small sample size or poorly fitting curves. This is complicates by the inclusion of mature individuals. Few studies adapting Demirjian's method provide sufficient or appropriate statistics to compare maturation of individual teeth. The wide 95% confidence intervals for maturity score by age, age by maturity score, age of individual tooth stages and large number of sequences suggest that the significant differences in dental maturity score do not reflect any biological difference in the timing of tooth formation stages at the population level. Demirjian's dental maturity method is inappropriate to assess population differences in dental maturity and adapting scores for age or age for scores for different groups of children is probably unnecessary. PMID- 20304572 TI - Sexual dimorphism in deciduous crown traits of a European derived Australian sample. AB - Sex determination of juvenile skeletal remains is a problematic area affecting physical anthropology, forensic science and archaeology. Sexual dimorphism in the morphometric crown traits of the deciduous dentition may be used to help resolve this issue. Dental stone casts from a European derived Australian sample (n=151) were used to investigate variation within crown traits of the deciduous canine and molars. The metric traits investigated were crown size, trigonid size and talonid size. The morphological features included Carabelli's trait and molar cusp number. Metric crown traits were significantly larger in males (p<0.05). The morphological crown traits were not significantly different between the sexes. The largest degree of sexual dimorphism was 11.11% in the trigonid mesiodistal diameter of the first deciduous molar. This is the first recording of the measurement in a European derived sample. Two multivariate statistics, linear functional discriminant analysis and binary logistic regression, were used to determine the success rate of sex classification from the crown traits. The most suitable was linear functional discriminant analysis, however similar results were found when using binary logistic regression. When using all variables investigated in this study, sex could be classified with accuracy of 70.2% from linear functional discriminant analysis (cross validated). The mandibular teeth had greater sexual dimorphism, classifying sex correctly 74.8% of the time compared to maxillary variables that had a success rate of 55.6%. Our results have shown that morphometric crown traits in the deciduous dentition can be used to classify sex of juvenile skeletons (11 months to 12 years) of European descent from linear functional discriminant analysis with accuracy between 70.2% and 74.8%. PMID- 20304573 TI - Indoors forensic entomology: colonization of human remains in closed environments by specific species of sarcosaprophagous flies. AB - Fly species that are commonly recovered on human corpses concealed in houses or other dwellings are often dependent on human created environments and might have special features in their biology that allow them to colonize indoor cadavers. In this study we describe nine typical cases involving forensically relevant flies on human remains found indoors in southern Finland. Eggs, larvae and puparia were reared to adult stage and determined to species. Of the five species found the most common were Lucilia sericata Meigen, Calliphora vicina Robineau-Desvoidy and Protophormia terraenovae Robineau-Desvoidy. The flesh fly Sarcophaga caerulescens Zetterstedt is reported for the first time to colonize human cadavers inside houses and a COI gene sequence based DNA barcode is provided for it to help facilitate identification in the future. Fly biology, colonization speed and the significance of indoors forensic entomological evidence are discussed. PMID- 20304574 TI - Odontology as a forensic science, the North American experience. AB - This chapter discusses the North American situation, primarily that of the United States judicial system. The United States was established as neither a monarchy nor a theocracy. An unofficial motto of the country has always been - the rule of laws, not of men (or deities). The primary source of law in the United States is the US Constitution. However, each of the 50 states has as its primary source of law a state constitution. In order to become a state, that constitution must conform to US Constitution. In the United States the US Congress, consisting of duly elected Representatives and Senators from the 50 states draft and pass Acts that establish (or direct to be established by officers of the Executive Branch following prescribed administrative procedures) federal law. Each state too, has its own legislative bodies and process for making law. Each state also has its own system of courts. In order to discuss the role of the odontologist within these systems, a primer on how these systems function and interact is crucial. This article discusses the functioning of those systems in relation to the practice of forensic odontology. PMID- 20304575 TI - [Late complication of surgical repair of aortic coarctation: ruptured pseudoaneurysm of the aorta treated by thoracic endovascular aortic repair]. AB - Aortic coarctation is a frequent congenital defect requiring early surgical treatment. Late complications of these surgical procedures can be fatal as in the case of a ruptured anastomotic pseudoaneurysm. We present a case of a 49-year-old man presenting with hemorrhagic shock due to this complication who was successfully treated by endovascular techniques with implantation of two stent grafts. This case illustrates the fact that endovascular aortic repair is feasible, certainly less invasive and very efficient for this type of complication when used in an experienced center. PMID- 20304576 TI - [Hospital information system and epidemiology. Abstracts of Adelf-Emois Colloquium. April 22-23, 2010. Bordeaux, France]. PMID- 20304577 TI - Use of total reflection X-ray fluorescence (TXRF) for the evaluation of heavy metal poisoning due to the improper use of a traditional ayurvedic drug. AB - An Indian patient referred to Clinica del Lavoro 'L.Devoto' of Milano showed clinical signs of heavy metal poisoning, possibly related to a sustained 6-month use of approx. 3 g/day of a traditional preparation (a whitish powder with a 'mineral' appearance) to treat urological problems. To confirm the causal relationship between the disease and the use of such product, metal testing was performed on the patient's hair and the ayurvedic remedy samples by total reflection X-ray fluorescence (TXRF). For TXRF analysis 1-cm cut of the patient's hair was directly deposited onto the quartz glass sample carrier, then 10 microl of nitric acid 65% were added and dried in air. TXRF showed high versatility, rapid and simultaneous element detection, and short analysis time, thus supporting a wider use in emergency medicine and in forensic analyses. PMID- 20304578 TI - A comprehensive review of Paget-Schroetter syndrome. AB - Venous thoracic outlet syndrome progressing to the point of axilosubclavian vein thrombosis, variously referred to as Paget-Schroetter syndrome or effort thrombosis, is a classic example of an entity which if treated correctly has minimal long-term sequelae but if ignored is associated with significant long term morbidity. The subclavian vein is highly vulnerable to injury as it passes by the junction of the first rib and clavicle in the anterior-most part of the thoracic outlet. In addition to extrinsic compression, repetitive forces in this area frequently lead to fixed intrinsic damage and extrinsic scar tissue formation. Once primary thrombosis is recognized, catheter-directed thrombolytic therapy is usually successful if initiated within ten to 14 days of clot formation, but often unmasks an underlying lesion. The vast majority of investigators believe that decompression of the venous thoracic outlet, usually by means of first rib excision, partial anterior scalenectomy, resection of the costoclavicular ligament, and thorough external venolysis, is necessary, although opinion is less uniform as to the need for and method of treatment of the venous lesion itself. Using this algorithm, long-term success rates of 95 to 100% have been reported by many investigators. This review, in addition to discussing the overall treatment algorithm in more detail, attempts to point out controversies that still exist and research directions, both clinical and basic, that need to be pursued. Prospective randomized trials addressing this entity are surprisingly lacking, and although there is consensus based on experience, it may be necessary to step back and rigorously explore several aspects of this entity. PMID- 20304579 TI - Endovascular treatment of aortoesophageal and aortobronchial fistulae. AB - BACKGROUND: Even when promptly recognized and treated, aortoesophageal (AEF) and aortobronchial (ABF) fistulae are highly lethal conditions. Open surgical repair also carries a high risk of mortality and morbidity. Several alternative strategies have been recently reported in the literature including thoracic endovascular aortic repair (TEVAR). However, relatively little is known about results of TEVAR for AEF and ABF due to their rarity and the lack of large surveys. METHODS: A voluntary national survey was conducted among Italian universities and hospital centers with an endovascular program. Questionnaires were distributed by e-mail to participating centers and aimed to evaluate the results of endovascular repair of established AEF or ABF. RESULTS: Seventeen centers agreed to participate and provided data on their patients. Between 1998 and 2008, a total of 1138 patients were treated with TEVAR. In 25 patients (2.2%), the indication to treatment was an AEF and/or an ABF. In 10 of these cases (40%), an associated open surgical procedure was also performed. Thirty-day mortality rate of AEF/ABF endovascular repair was 28% (7 cases). No cases of paraplegia or stroke were observed. Mean follow-up was 22.6 months (range, 1-62). Actuarial survival at 2 years was 55%. Among the 18 initial survivors, five patients (28%) underwent reintervention due to late TEVAR failure. CONCLUSIONS: Stent grafting for AEF and ABF represents a viable option in emergent and urgent settings. However, further esophageal or bronchial repair is necessary in most cases. Despite less invasive attempts, mortality associated with these conditions remains very high. PMID- 20304580 TI - National trends in venous disease. AB - BACKGROUND: The national burden of venous disease and use of ultrasound (US) in the outpatient and emergency department (ED) settings has not been well described. The objective of this study is to describe venous disease in the outpatient and ED settings nationally as well as to characterize the use of US for diagnosis of venous disease, including phlebitis. METHODS: Data from the 1997 to 2006 National Ambulatory Medical Care Survey (NAMCS) and National Hospital Ambulatory Medical Care Survey (NHAMCS) were compiled, and complex sampling methods were used to describe the number of outpatient and ED visits for adults given a diagnosis of venous disease or phlebitis by ICD-9 coding. Logistic regression analysis with calculated odds ratios are used to examined patient visit characteristics and use of US. RESULTS: During the 10 years studied, an office or ED visit for venous disease occurred over 46 million times, for an average of 4.6 million visits per year, with this rate increasing from 4.03 million to 5.71 million per year (odds ratio [OR] 1.01, confidence interval [CI] 1.00-1.01). The majority of these patients were seen by specialists, such as surgeons or cardiologists, but a significant number were also seen by primary care providers (PCP). There were 2 million office visits (PCP and specialists) on average per year with no significant increase. There were approximately 236,000 ED visits for deep vein thrombosis (DVT) on average per year, which showed a small increase (OR 1.01, CI 1.00-1.01). Visits for DVT and phlebitis were as likely to be seen by PCPs as ED physicians. Non-DVT venous disease is much more likely to be seen by a surgeon (OR 4.88, CI 3.53-6.74) than a PCP. DVT is much less likely to be diagnosed by a specialist (OR 0.27, CI 0.18-0.29) than a PCP. Insurance status and geographic region were not associated with DVT or non-DVT venous disease diagnosis. CONCLUSIONS: Nationally, a significant and growing number of patients with venous disease are being seen in the outpatient setting by PCPs and specialists. A significant number of patients with DVT are being seen in the outpatient setting, but without a trend away from care in the ED over the 10-year study period. Additionally, the majority of patients with DVT diagnosis do not seem to be getting ultrasounds at the same visit. Many of these patients are being seen by PCPs who may require additional training and infrastructure for appropriate patient care. PMID- 20304581 TI - Insulin use is associated with poor limb salvage and survival in diabetic patients with chronic limb ischemia. AB - OBJECTIVE: The goal was to compare the outcomes in patients with disabling claudication (DC) or critical limb ischemia (CLI) to determine if diabetics (DM) have poorer patency, limb salvage (LS), and survival rates than nondiabetic patients and if the diabetic regimen affects these outcomes. METHODS: All patients who presented with DC or CLI between June 2001 and September 2008 were included. Non-DM patients were compared with those with DM who are currently managed by diet only or oral medications (D-OM), oral medications plus insulin (OM+INS), or insulin alone (INS). RESULTS: Of the 746 patients (886 limbs), there were 406 patients (464 limbs) in non-DM, 96 patients (135 limbs) in D-OM, 98 patients (118 limbs) in OM+INS, and 146 patients (185 limbs) in INS groups. There were more patients with coronary artery disease, hypertension, and renal insufficiency in the DM group than non-DM, with the INS group having the highest incidence of renal insufficiency/dialysis (46%/20%). Gangrene and foot sepsis were significantly more frequent in patients in OM+INS (45%/3%) and INS (50%/6%) than non-DM (15%/0.2%) and D-OM groups (25%/1%; P < .001). More patients in the INS group (14%) and OM+INS (9%) had primary amputation than non-DM (4%) and D-OM (4%; P < .01). Mean follow-up was 26.3 +/- 20.7 months. Overall survival following revascularization was similar in D-OM and non-DM and OM+INS and INS, the latter being significantly worse (P < .001). The LS rate in D-OM and non-DM was also identical, whereas OM-INS and INS had significantly worse LS, with OM INS marginally better than INS (P = .094). Primary patency (PP) was worse in endovascular-treated patients on insulin than non-DM and D-OM patients (P < .001), whereas PP was similar between groups in open-treated patients. Multivariate analysis showed that coronary artery disease, renal insufficiency, chronic obstructive pulmonary disease, indication for intervention, insulin use, nonambulatory status, and statin drug non-use were independently associated with decreased survival, whereas insulin use, presence of gangrene, need for infrapopliteal interventions, and nonambulatory status were independently associated with limb loss. TransAtlantic Inter-Society Consensus (TASC) classification of the treated lesions being C or D, infrapopliteal interventions, and indication of intervention (DC vs CLI) were independently associated with primary patency, whereas insulin use was not. CONCLUSIONS: Diabetic patients who present with limb ischemia can be subdivided into three distinct subgroups based on their diabetic regimen. The survival and LS rates of those controlled with diet or OM are nearly identical to nondiabetics, both of which are significantly better than OM+INS or INS. The PP rate in endovascular-treated patients is worse in patients who are on insulin. Being on insulin is independently associated with decreased survival and limb loss but not PP. PMID- 20304582 TI - Endovascular management of multiple arteriovenous fistulae following failed laser assisted pacemaker lead extraction. AB - A woman presented for evaluation of new-onset left arm edema after failed laser assisted pacemaker lead extraction. Initial workup demonstrated a left subclavian artery to vein arteriovenous fistula (AVF). She underwent repair of the AVF with placement of a covered stent in the subclavian artery, however, her symptoms did not completely resolve. Investigation revealed a left common carotid artery to left innominate vein AVF, which was repaired by deploying a covered stent retrograde into the left common carotid artery. Her symptoms subsequently resolved. Multiple iatrogenic AVF can be repaired endovascularly, however, a high degree of suspicion for multiple injuries should be maintained. PMID- 20304583 TI - Trends in vena caval interruption. AB - OBJECTIVE: This study examined the national use of vena cava filters (VCFs) from 1998 to 2005. METHODS: Methods for complex surveys were used to examine hospital discharge data from the Nationwide Inpatient Sample (NIS) to determine the use of VCFs for the years 1998 to 2005. VCF placement in the absence of deep venous thrombosis (DVT) or pulmonary embolus (PE) was categorized as prophylactic. RESULTS: During the study period, the estimated rate of hospitalizations per year with a diagnosis of DVT (odds ratio [OR], 1.025; 95% confidence interval [CI], 1.019-1.032; P < .01) or PE (OR, 1.076; 95% CI, 1.069-1.083; P < .01) rose significantly. The estimated weighted frequency of VCF placement increased from 52,860 procedures in 1998 to 104,114 procedures in 2005 (0.15% and 0.27% of all discharges, respectively), representing an 80% increase. VCF placement significantly increased during hospitalizations with any diagnosis of DVT or PE, or both, and no DVT or PE (P < .01 for each). Logistic regression models revealed that the rate of prophylactic VCF placement increased at a significantly higher rate than VCF placement associated with DVT or PE (157% vs 42%; P < .01), after adjusting for age, gender, and hospital characteristics. Prophylactic VCF placement in the setting of morbid obesity (P < .01) and head injury (P = .03) rose significantly over time. CONCLUSIONS: From 1998 to 2005, the estimated rates of prophylactic VCF placement increased at a significantly higher rate than VCF placement in the setting of DVT or PE. Significant increases in the use of prophylactic VCFs were seen in the setting of morbid obesity and head injury. PMID- 20304584 TI - Ferritin levels, inflammatory biomarkers, and mortality in peripheral arterial disease: a substudy of the Iron (Fe) and Atherosclerosis Study (FeAST) Trial. AB - BACKGROUND: This study delineated correlations between ferritin, inflammatory biomarkers, and mortality in a cohort of 100 cancer-free patients with peripheral arterial disease (PAD) participating in the Veterans Affairs (VA) Cooperative Study #410, the Iron (Fe) and Atherosclerosis Study (FeAST). FeAST, a prospective, randomized, single-blind clinical trial, tested the hypothesis that reduction of iron stores using phlebotomy would influence clinical outcomes in 1227 PAD patients randomized to iron reduction or control groups. The effects of statin administration were also examined in the Sierra Nevada Health Care (SNHC) cohort by measuring serum ferritin levels at entry and during the 6-year study period. No difference was documented between treatment groups in all-cause mortality and secondary outcomes of death plus nonfatal myocardial infarction and stroke. Iron reduction in the main study caused a significant age-related improvement in cardiovascular disease outcomes, new cancer diagnoses, and cancer specific death. METHODS: Tumor necrosis factor (TNF)-alpha, TNF-alpha receptors 1 and 2, interleukin (IL)-2, IL-6, IL-10, and high-sensitivity C reactive protein (hs-CRP) were measured at entry and at 6-month intervals for 6 years. Average levels of ferritin and lipids at entry and at the end of the study were compared. The clinical course and ferritin levels of 23 participants who died during the study were reviewed. RESULTS: At entry, mean age of entry was 67 +/- 9 years for the SNHCS cohort, comparable to FeAST and clinical and laboratory parameters were equivalent in substudy participants randomized to iron reduction (n = 51) or control (n = 49). At baseline, 53 participants on statins had slightly lower mean entry-level ferritin values (114.06 ng/mL; 95% confidence interval [CI] 93.43 134.69) vs the 47 off statins (127.62 ng/mL; 95% CI, 103.21-152.02). Longitudinal analysis of follow-up data, after adjusting for the phlebotomy treatment effect, showed that statin use was associated with significantly lower ferritin levels ( 29.78 ng/mL; Cohen effect size, -0.47 [t(df, 134) = 2.33, P = .02]). Mean follow up average ferritin levels were higher in 23 participants who died (132.5 ng/mL; 95% CI, 79.36-185.66) vs 77 survivors (83.6 ng/mL; 95% CI, 70.34-96.90; Wilcoxon P = .05). Mean follow-up IL-6 levels were higher in dead participants (21.68 ng/mL; 95% CI, 13.71-29.66) vs survivors (12.61 ng/mL; 95% CI, 10.72-14.50; Wilcoxon P = .018). Ferritin levels correlated (Pearson) with average IL-6 levels (r = 0.1845; P = .002) and hsCRP levels (r = .1175; P = .04) during the study. CONCLUSION: These data demonstrate statistical correlations between levels of ferritin, inflammatory biomarkers, and mortality in this subset of patients with PAD. PMID- 20304585 TI - Combined endovascular and open operative approach for mycotic carotid aneurysm. AB - Mycotic aneurysms of the extracranial carotid artery are rare and warrant surgical intervention. Management involves open and endovascular approaches. We report the case of a 67-year-old woman with an Escherichia coli soft-tissue infection of the right retropharyngeal space and subsequent mycotic carotid aneurysm and thrombosis of the internal jugular vein. The patient presented with a pulsatile mass and right middle cerebral artery stroke. Our surgical management involved coil embolization of the aneurysm to provide for vascular control, with resection of the common carotid artery, internal carotid artery, and extracranial carotid artery branches, along with the internal jugular vein. PMID- 20304586 TI - Open or percutaneous revascularization for chronic splanchnic syndrome. AB - BACKGROUND: Treatment of chronic splanchnic syndrome remains controversial. In the past 10 years, endovascular repair (ER) has replaced open repair (OR) to some extent. This evidence summary reviews the available evidence for ER or OR of chronic splanchnic syndrome. METHODS: A systematic literature search of MEDLINE database was performed to identify all studies that evaluated treatment of chronic splanchnic syndrome between 1988 and 2009. RESULTS: The best available evidence consists of prospectively accumulated but retrospectively analyzed data with a high risk for confounding. Only a few of these studies incorporated functional tests to assess splanchnic ischemia before or after treatment. ER has the advantage of low short-term morbidity but the disadvantage of decreased long term primary patency compared with OR. ER and OR have similar rates of secondary patency, although the reintervention rate after ER is higher. CONCLUSION: ER appears to be preferential in the treatment of elderly patients and in patients with comorbidity, severe cachexia, or hostile abdomen. Long-term results after OR are excellent. OR can still be proposed as the preferred option for relatively young and fit patients. PMID- 20304587 TI - Persistence of intra-aortic air after circulatory arrest. PMID- 20304588 TI - Process of care for carotid endarterectomy: perioperative medical management. AB - Carotid endarterectomy (CEA) has been repeatedly described as a safe and efficacious procedure to provide a stroke-risk reduction benefit in both symptomatic and asymptomatic cases. Contemporary outcomes are acceptable using the large-scale randomized trials as a metric of success. Class I and II data can be applied to improve the care process of patients undergoing CEA. Myocardial infarction remains the most significant nonstroke complication; however, there is no significant benefit to noninvasive stress testing in patients with clinically stable disease. Perioperative beta-blockade may offer up to a 10-fold reduction in the rate of perioperative myocardial infarction, but deleterious effects are attributable to high-dose regimens. Angiotensin blockade has been shown to reduce cardiovascular mortality in patients with atherosclerosis by up to 25%, although few studies have examined these agents directly in carotid surgery patients. Statins are beneficial to patients undergoing CEA with trials demonstrating up to a 3% absolute reduction in the incidence of stroke following CEA. Aspirin therapy is associated with an up to 7% absolute reduction in early stroke following CEA; however, the efficacy of combination or high-dose antiplatelet therapy remains ill-defined. A treatment strategy that involves perioperative medical optimization is likely to improve surgical outcomes and long-term cardiovascular risk for patients undergoing CEA. PMID- 20304589 TI - Endovascular repair compared with surveillance for patients with small abdominal aortic aneurysms. AB - BACKGROUND: Although repair of large abdominal aortic aneurysms (AAAs) is well accepted, randomized clinical trials have failed to demonstrate benefit for early surgical repair of small aneurysms compared with surveillance. Endovascular repair has been shown to be safer than open surgical repair in patients with large aneurysms, prompting a randomized trial of early endovascular repair vs surveillance in patients with small aneurysms. METHODS: We randomly assigned 728 patients (13.3% women; mean age, 71 +/- 8 years) with 4 to 5 cm AAAs to early endovascular repair (366 patients) or ultrasound surveillance (362 patients). Rupture or aneurysm-related death and overall mortality in the two groups were compared during a mean follow-up of 20 +/- 12 months. RESULTS: Among patients randomized to treatment, 89% underwent aneurysm repair. Among patients randomized to surveillance, 31% underwent aneurysm repair during the course of the study. After a mean follow-up of 20 +/- 12 months (range, 0-41 months), 15 deaths had occurred in each group (4.1%). The unadjusted hazard ratio (95% confidence interval) for mortality after early endovascular repair was 1.01 (0.49-2.07, P = .98). Aneurysm rupture or aneurysm-related death occurred in two patients in each group (0.6%). The unadjusted hazard ratio was 0.99 (0.14-7.06, P = .99) for early endovascular repair. CONCLUSIONS: Early treatment with endovascular repair and rigorous surveillance with selective aneurysm treatment as indicated both appear to be safe alternatives for patients with small AAAs, protecting the patient from rupture or aneurysm-related death for at least 3 years. PMID- 20304590 TI - Aortic customize: a new alternative endovascular approach to aortic aneurysm repair using injectable biocompatible elastomer. An in vitro study. AB - PURPOSE: Aortic Customize is a new concept for endovascular aortic aneurysm repair in which a non polymerized elastomer is injected to fill the aneurysm sac around a balloon catheter. The aim of this in vitro study was to investigate the extent of aneurysm wall stress reduction by the presence of a noncompliant elastomer cuff. METHODS: A thin-walled latex aneurysm (inner radius sac 18 mm, inner radius neck 8 mm), equipped with 12 tantalum markers, was attached to an in vitro circulation model. Fluoroscopic roentgenographic stereo photogrammetric analysis (FRSA) was used to measure marker movement during six cardiac cycles. The radius of three circles drawn through the markers was measured before and after sac filling. Wall movement was measured at different systemic pressures. Wall stress was calculated from the measured radius (sigma = pr/2t). RESULTS: The calculated wall stress was 7.5-15.6 N/cm(2) before sac filling and was diminished to 0.43-1.1 N/cm(2) after sac filling. Before sac filling, there was a clear increase (P < .001) in radius of the proximal (range, 7.9%-33.5%), middle (range, 3.3%-25.2%), and distal (range, 10.5%-184.3%) rings with increasing systemic pressure. After sac filling with the elastomer, there remained a small, significant (P < .001) increase in the radius of the circles (ranges: 6.8%-8.8%; 0.7%-1.1%; 5.3%-6.7%). The sac filling reduced the extent of radius increase. The treated aneurysm withstood systemic pressures up to 220/140 mm Hg without noticeable wall movement. After the sac filling, there was no pulsation visible in the aneurysm wall. CONCLUSIONS: Filling the aneurysm sac of a simplified in vitro latex model with a biocompatible elastomer leads to successful exclusion of the aneurysm sac from the circulation. Wall movement and calculated wall stress are diminished noticeably by the injection of biocompatible elastomer. PMID- 20304592 TI - Retrospective evaluation of the need of a redo surgery at the groin for the surgical treatment of varicose vein. AB - BACKGROUND: Surgical treatment for varicose recurrence (STVR) involves removing all sources of reflux from the deep venous network to the superficial venous network. STVR is usually more complex and aggressive than first-line treatment by stripping, particularly for redo surgery at the groin (RSG). This retrospective study compared traditional STVR and a less aggressive surgical approach focusing on treatment of the varicose reservoir and avoiding RSG if possible. METHOD: Two successive periods of STVR after great saphenous vein stripping were compared: traditional STVR (T1) and STVR focusing on the varicose reservoir (T2). We reviewed postoperative complications and studied the hemodynamic and clinical results. RESULTS: During T1 and T2, we operated 473 legs in 288 patients (236 women, 52 men) to treat varicose recurrence after great saphenous vein stripping. Mean age was 60.83 years (range, 28-88 years). We operated on 137 patients during T1 and 151 during T2. Patients had similar demographic data, CEAP classification, and Venous Disability Score. Inguinal reflux occurred in 73.9% of T1 patients and in 74.4% of T2 patients. We performed RSG in 66.0% of T1 patients and in 2.2% of T2 patients (P < .05). We did not use echo-guided sclerotherapy in addition to primary STVR. Tumescent local anesthesia was used in 96.2% of STVR in T2 vs 4.0% in T1 (P < .05), and 95.3% of T2 procedures were outpatient vs 13.7% of T1 (P < .05). Outcomes of limbs presenting an inguinal reflux treated with RSG during T1 (group 1) and without RSG during T2 (group 2) were compared. Postoperative complications occurred in 6.7% in group 1 vs 0.5% in group 2 (P < .05), with inguinal complications predominating. The mean cost of the procedure per limb was euro1,195.88 in group 1 vs euro863.08 in group 2 (P < .0001). After 3 years of follow-up, Kaplan-Meier life-table analysis showed group 1 and 2 patients had similar rates of freedom from inguinal reflux (90.8% vs 92.9% survival rate) and from varicose repeat-recurrence (90.8% vs 91.9% survival rate). Group 1 had better results for the Venous Disability Score (0.38 vs 0.58, P = .02) and cosmetic improvement (94.2% vs 84.2%; P = .00032). CONCLUSION: STVR focusing on the varicose reservoir and avoiding RSG led to a minimally invasive procedure and a reduction in postoperative complications, with good medium-term clinical and hemodynamic results, particularly for symptoms improvement and cosmetic appearance, with a lower cost vs traditional STVR with RSG. PMID- 20304593 TI - Endoscopic basilic vein transposition for hemodialysis access. AB - BACKGROUND: Hemodialysis access by autogenous arteriovenous fistulas (AVFs) is generally recommended due to lower mortality, morbidity, and cost vs graft and catheter use. Many dialysis patients lack the common superficial veins used for standard AVF options and require transposition of a deep vein for autogenous dialysis access through a long open incision (open/AVF-T). These operations may require prolonged time for healing, thus extending catheter-based dialysis. We report our experience with minimally invasive techniques for creating AVF-Ts using an endoscopic procedure (endo/AVF-T). METHODS: We reviewed our vascular access database of consecutive access operations to identify consecutive patients with endo/AVF-Ts. For comparison, we also reviewed the immediate preceding traditional open/AVF-T operations that we previously reported. We evaluated demographics, time to access use, and primary, assisted, and cumulative patency. RESULTS: We identified 100 consecutive endo/AVF-T operations attempted, and 98 were technically successful. The analysis excluded two conversions to successful open/AVF-T. The mean age of the 98 patients in the endo/AVF-T study group was 60 years (range, 22-94 years), 59 (60.2%) were women, 48 (49.0%) were diabetic, 20 (20.4%) were obese, and 52 (53.1%) had had previous access surgery. Mean time to initial use of the access for endo/AVF-Ts was 6 weeks for primary and 12 weeks for staged transpositions. Mean follow-up was 14 months (range, 1-30 months). The 12- and 24-month cumulative patencies were 95.5% and 88.6%. The 78 traditional open/AVF-T operations from our previous report were reviewed for comparison. The mean age was 62 years (range, 18-83 years), 57 (73.1%) were women, 44 (56.4%) were diabetic, 15 (19.2%) were obese, and 46 (59.0%) had previous access surgery. Mean time to initial use of the access for open/AVF-Ts was 8 weeks for primary and 16 weeks for staged operations. Mean follow-up was 18 months (range, 3-48 months). The 12- and 24-month cumulative patencies were 96.0 and 88.9%. No grafts were used in any patient during the study period. CONCLUSION: Time to access use was less with endoscopic AVF-T (P < .01) for both primary and staged operations. Primary, assisted, and cumulative patency rates were the same for open and technically successful endoscopic transpositions. Endoscopic AVF-Ts offer a viable alternative to open AVF-Ts. PMID- 20304594 TI - Eight-year institutional review of carotid artery stenting. AB - OBJECTIVES: Vascular surgeons have increasingly become proficient in carotid artery stenting (CAS) as an alternative treatment modality for cervical carotid artery occlusive disease. We analyzed our early and late outcomes of CAS over the last 8 years. METHODS: We report a single-center retrospective review of 388 carotid bifurcation lesions treated with CAS using cerebral embolic protection from May 2001 to July 2009. Data analysis includes demographics, procedural records, duplex exams, arteriograms, and two-view plain radiographs over a mean follow-up time of 23.0 months (interquartile range, 10.9-35.4). RESULTS: At the time of treatment, the mean age of the entire cohort (76% men and 24% women) is 71 years; 13% were >/=80 years of age, and 31% had a prior history of either carotid endarterectomy (CEA) and/or external beam neck irradiation (XRT). The mean carotid stenosis is 80%, and asymptomatic lesions represent 69% of the group. Overall 30-day rates of death, stroke, and myocardial infarction are 0.5%, 1.8%, and 0.8%, respectively. The combined death/stroke rate at 30 days is 2.3%. The 30-day major/minor stroke rates for analyzed subgroups are statistically significant only for XRT/recurrent stenosis vs de novo lesions, 0% and 2.6% (P = .03), but not for asymptomatic vs symptomatic patients, 1.9% and 1.7% (P = .91) and age <80 vs >/=80, 2.0% and 1.8% (P = .52), respectively. At long-term, the freedom from all strokes at 12, 24, 36, and 48 months was 99.2%, 97.6%, 96.7%, and 96.7%, respectively. At late follow-up, the restenosis rate is 3.5%. Restenosis rates for recurrent stenosis/XRT vs de novo lesions are 2.7% and 3.4% (P = .39). Among the restenotic lesions were two associated type III stent fractures in de novo lesions, both of which were closed-cell stents. An additional two other type I fractures have been identified, yielding a stent fracture rate of 5.5%. The late death rate for the entire group is 16.8%, with one stent-related death secondary to ipsilateral stroke at 20 months (0.3% death rate). CONCLUSIONS: Vascular surgeons performing CAS with embolic protection can achieve good early and late outcomes that are comparable to CEA benchmarks. Late stent failures (stroke, restenosis, and/or stent fatigue), while uncommon, are a recognized delayed problem. PMID- 20304596 TI - [Gestational hypertensions: definitions and consequences in outcome of pregnancy]. AB - Hypertensive pathologies during pregnancy lack definition. Meanwhile, we can offer the following definitions: - Gestational hypertension (GHT): Systolic HT >or= 140 mmHg and/or diastolic blood pressure 90 mmHg. Which occur beyond the 20th week of amenorrhea and fading before the 42nd day postpartum. - Preeclampsia: Systemic HT associated with a proteinuria (> 0,3 g/24 h) also arising beyond the 20th week of amenorrhea and resolving by the 6th week postpartum. However, in the setting of a GHT associated with a number of abnormal signs & symptoms (i.e. hyper-reflexia, epigastric pain, etc.) and/or abnormal biological values (i.e. raised transaminase levels, thrombocytopenia, hyperuricaemia, haemolysis) and/or IUGR, PE must be considered until proven otherwise. - HELLP syndrome: Association of haemolysis, elevated liver enzymes (transaminases & LDH) and thrombocytopenia. However, HELLP syndrome can exist without haemolysis. - Eclampsia is defined as the occurrence of tonic-clonic seizures in a setting of GHT. Assessing the morbidity and mortality of both the mother and the foetus, in the setting of GHT, is a challenge because of the absence of registry, and because of the high amount of bias (gestational age, birth weight, presence or absence of risk factors in the studied population, belonging to a developed or a developing nation, etc.) which all account for the large discrepancies in the results to such an extent that the relative risk to the mother can vary from simple to the double, and the foetal risks are highly variable from one study to the next. PMID- 20304597 TI - [Superficial venous malformations]. AB - Superficial venous malformations are part of a larger group now called superficial vascular anomalies and previously known as angiomas. These include vascular tumors or infantile hemangioma, low-flow vascular malformations (capillary, lymphatic, and superficial venous malformations) and high-flow vascular malformations (arteriovenous malformations). Some of these lesions are complex. This classification facilitates their multidisciplinary therapeutic management. Embolization is an effective curative treatment for malformations of small and intermediate size. The objective for large or complex malformations is to restore anatomic function and improve cosmetic results. PMID- 20304599 TI - [Meningitis and loss of visual acuity]. PMID- 20304600 TI - [Letter on the article "First steps towards a comparative evaluation of the French medical schools"]. PMID- 20304601 TI - Incision infection with Mycobacterium tuberculosis after total hip arthroplasty without any primary tuberculosis focus. AB - We describe a case of a tuberculous abscess unassociated with other clinical features of tuberculosis in a 46-year-old woman with a history of 4 hip surgeries plus total hip arthroplasty (THA) due to developmental hip dislocation. Four months after THA, she developed a collection at the incision site for which specimens produced positive culture findings for Mycobacterium tuberculosis. We could not detect any primary focus of tuberculosis anywhere in the patient's body. We performed soft-tissue debridement and drainage completely above the fascia lata to remove pus. The infection recurred twice despite chemotherapy and the earlier treatment. At a 6-year follow-up examination, there was no sign of either tuberculosis or prosthetic loosening. To our knowledge, this is the first report of localized tuberculous abscess within a THA incision. PMID- 20304602 TI - Mindfulness and experiential avoidance as predictors of posttraumatic stress disorder avoidance symptom severity. AB - Mindfulness reflects an awareness of present moment experiences through an attitude of acceptance and openness (Bishop et al., 2004; Cardaciotto, Herbert, Forman, Moitra, & Farrow, 2008). Experiential avoidance, by contrast, refers to attempts to change, alter, or avoid private experiences (e.g., thoughts, feelings, sensations), and it is believed to underlie a number of psychopathologies, including PTSD (Hayes, Wilson, Gifford, Follette, & Strosahl, 1996). We were interested in the ability of mindfulness to predict the variance of PTSD avoidance symptom severity above and beyond experiential avoidance. 378 introductory psychology students were administered self-report measures of PTSD, mindfulness, experiential avoidance, thought suppression, alexithymia, and avoidant coping. Mindfulness, specifically nonjudgment of experiences, accounted for a unique portion of the variance in PTSD avoidance symptoms. PMID- 20304603 TI - Risk factors of children who exited from an early intervention program without an identified disability and returned with a developmental disability. AB - A retrospective cohort study was undertaken to identify risk factors for children at greatest risk of delayed diagnosis of developmental disability. Two thousand four hundred and thirty-nine children were selected for this study due to their participation in the California Early Start (ES) Program in 1998. Comparisons were made among children that had no break in services offered through the ES Program versus children that returned with a disability after exiting the ES Program. Factors examined include child's condition and qualifying risk factors, mother's demographic characteristics, family's risk factors, and risk scores developed for each county in which the family resided. Children with a delay in diagnosis of a disability have characteristics that fall outside the norm for the identification of a disability. It is not clear if this is related to age specific manifestation to the appearance of a disability or to conditions difficult to diagnose. PMID- 20304604 TI - Identification of common nail and skin disorders. AB - NARRATIVE REVIEW: The following review discusses the more common disorders of the perionychium and skin likely to be observed by the hand therapist. To assist the therapist in recognition of abnormalities, the anatomy, physiology, and basic function of the normal nail unit are described. Indications of when disorders of the nail, resulting from trauma, infections, and neoplasms, require referral to another practitioner are discussed. Characteristics of abnormal skin conditions are described with an emphasis on differentiating benign from malignant lesions. By knowing the suspicious characteristics of nail and skin disorders, the upper extremity therapist can positively impact the well-being of his or her patients through quick referral, leading to early diagnosis and treatment of potentially serious disease. LEVEL OF EVIDENCE: 5. PMID- 20304605 TI - Screening and evaluation of the cardiovascular and pulmonary systems in patients presenting with upper extremity impairments. AB - NARRATIVE REVIEW: Given the prevalence of cardiovascular and pulmonary (CV-P) disease, it is likely that a substantial portion of patients seeking services from hand therapists have diagnosed or yet to be diagnosed disease in one or both of these systems. Pain originating from these systems is more common in the chest, shoulder, and scapular regions, but both systems can refer pain into the medial aspect of the forearm and hand. Pancoast's tumors of the lung, myocardial ischemia, and myocardial infarction are examples of specific pathologies capable of referring pain into these upper extremity regions. Another concern for the hand therapist is that upper extremity exercise is more stressful on the cardiovascular system than lower extremity exercise. Because of this, hand therapists need to be able to recognize when to discontinue or modify exercise interventions based on inappropriate cardiovascular system responses. Thus, the purpose of this review is to present 1) screening for potential pathology in the CV-P systems, 2) methods typically available to hand therapists for monitoring these systems, 3) criteria that indicate the need for therapy modification or medical referral, and 4) symptomatology of some common cardiac and pulmonary pathologic conditions the hand therapist may encounter. LEVEL OF EVIDENCE: 5. PMID- 20304606 TI - Studywise minimization: a treatment allocation method that improves balance among treatment groups and makes allocation unpredictable. AB - OBJECTIVES: In randomized controlled trials with many potential prognostic factors, serious imbalance among treatment groups regarding these factors can occur. Minimization methods can improve balance but increase the possibility of selection bias. We described and evaluated the performance of a new method of treatment allocation, called studywise minimization, that can avoid imbalance by chance and reduce selection bias. STUDY DESIGN AND SETTING: The studywise minimization algorithm consists of three steps: (1) calculate the imbalance for all possible allocations, (2) list all allocations with minimum imbalance, and (3) randomly select one of the allocations with minimum imbalance. We carried out a simulation study to compare the performance of studywise minimization with three other allocation methods: randomization, biased-coin minimization, and deterministic minimization. Performance was measured, calculating maximal and average imbalance as a percentage of the group size. RESULTS: Independent of trial size and number of prognostic factors, the risk of serious imbalance was the highest in randomization and absent in studywise minimization. The largest differences among the allocation methods regarding the risk of imbalance were found in small trials. CONCLUSION: Studywise minimization is particularly useful in small trials, where it eliminates the risk of serious imbalances without generating the occurrence of selection bias. PMID- 20304607 TI - Sampling and ethical issues in a multicenter study on health of people with intellectual disabilities. AB - OBJECTIVES: To study health inequalities in persons with intellectual disabilities, representative and unbiased samples are needed. Little is known about sample recruitment in this vulnerable group. This study aimed to determine differences in ethical procedures and sample recruitment in a multicenter research on health of persons with intellectual disabilities. Study questions regarded the practical sampling procedure, how ethical consent was obtained in each country, and which person gave informed consent for each study participant. STUDY DESIGN AND SETTING: Exploratory, as part of a multicenter study, in 14 European countries. After developing identical guidelines for all countries, partners collected data on health indicators by orally interviewing 1,269 persons with intellectual disabilities. Subsequently, semistructured interviews were carried out with partners and researchers. RESULTS: Identification of sufficient study participants proved feasible. Sampling frames differed from nationally estimated proportions of persons with intellectual disabilities living with families or in residential settings. Sometimes, people with intellectual disabilities were hard to trace. Consent procedures and legal representation varied broadly. Nonresponse data proved unavailable. CONCLUSION: To build representative unbiased samples of vulnerable groups with limited academic capacities, international consensus on respectful consent procedures and tailored patient information is necessary. PMID- 20304608 TI - Randomized trial showed that an "embedded" survey strategy optimized authorization rates compared with two "after survey" strategies in veterans with PTSD. AB - OBJECTIVES: To test methods to optimize mail survey response and authorization rates (i.e., allowing one's survey to be linked to medical records) when the survey is sensitive and the targeted population has a mental disorder. STUDY DESIGN AND SETTING: Randomized controlled trial of 1,099 veterans treated for posttraumatic stress disorder (PTSD) at a Midwestern Veteran Affairs Medical Center. Subjects were randomized to one of three groups: (1) Health Insurance Portability and Accountability Act (HIPAA) authorization form embedded in the survey (checking "yes" for consent); (2) HIPAA form requiring signature for consent sent after the survey; or (3) HIPAA form requiring a signature and social security number (SSN) for consent sent after the survey. RESULTS: The "embedded" strategy yielded the lowest survey response rate (67.5%) but highest authorization rate (59.1%). Requiring respondents' signatures and SSNs after the survey was returned generated the highest survey response rate (74.2%) but lowest authorization rate (48.7%). However, the response rate difference was not statistically significant. Reported emotional upset was low (1.5%) and primarily directed to the survey, not the HIPAA form. Older age and greater trustfulness were associated with higher authorization rates. CONCLUSION: Even with our most optimized strategy, authorization rates were disappointingly low. PMID- 20304609 TI - Logistic regression had superior performance compared with regression trees for predicting in-hospital mortality in patients hospitalized with heart failure. AB - OBJECTIVE: To compare the predictive accuracy of regression trees with that of logistic regression models for predicting in-hospital mortality in patients hospitalized with heart failure. STUDY DESIGN AND SETTING: Models were developed in 8,236 patients hospitalized with heart failure between April 1999 and March 2001. Models included the Enhanced Feedback for Effective Cardiac Treatment and Acute Decompensated Heart Failure National Registry (ADHERE) regression models and tree. Predictive accuracy was assessed using 7,608 patients hospitalized between April 2004 and March 2005. RESULTS: The area under the receiver operating characteristic curve for five different logistic regression models ranged from 0.747 to 0.775, whereas the corresponding values for three different regression trees ranged from 0.620 to 0.651. For the regression trees grown in 1,000 random samples drawn from the derivation sample, the number of terminal nodes ranged from 1 to 6, whereas the number of variables used in specific trees ranged from 0 to 5. Three different variables (blood urea nitrogen, dementia, and systolic blood pressure) were used for defining the first binary split when growing regression trees. CONCLUSION: Logistic regression predicted in-hospital mortality in patients hospitalized with heart failure more accurately than did the regression trees. Regression trees grown in random samples from the same data set can differ substantially from one another. PMID- 20304611 TI - Prevalence of diabetes and antipsychotic prescription patterns in patients with schizophrenia: a nationwide retrospective cohort study. AB - INTRODUCTION: Despite an increasing concern that atypical antipsychotics seem to have a stronger diabetogenic risk than conventional antipsychotics, little information is available on the prevalence of diabetes among schizophrenia patients, and prescription patterns for patients with comorbid schizophrenia and diabetes in Japan. OBJECTIVES: To compare the prevalence of diabetes between schizophrenia patients and the general population and to investigate whether diabetes status correlates the prescription patterns of antipsychotics at hospital discharge. METHODS: Schizophrenia patients who were discharged between April 2004 and March 2005 and who continued to receive outpatient treatment from 526 hospitals were included in this retrospective open cohort study. We collected information about the doctor diagnosis of diabetes during hospitalization, and drug prescriptions for schizophrenia at hospital discharge using medical charts. RESULTS: The overall prevalence of diabetes was 8.6% among patients with schizophrenia. Compared with the general population, the estimates of diabetes prevalence in the schizophrenia population were 2.6-10.8 percentage point higher among males aged 30-49 years, and 1.9-9.9 percentage point higher among females aged 40-59 years. The odds of being prescribed conventional antipsychotics were about 2 times higher among patients with diabetes than without diabetes, relative to atypical and combination of conventional and atypical antipsychotics. These results were robust across various sensitivity analyses. CONCLUSION: When treating schizophrenia patients with preexisting diabetes, psychiatrists need to monitor the occurrence of diabetes regularly regardless of antipsychotic class, strike a balance, and provide the most efficacious antipsychotic medication. PMID- 20304610 TI - Involvement of nitric oxide-cGMP pathway in the anticonvulsant effects of lithium chloride on PTZ-induced seizure in mice. AB - Lithium is still the mainstay in the treatment of affective disorders as a mood stabilizer. Lithium also shows some anticonvulsant properties. While the underlying mechanisms of action of lithium are not yet exactly understood, we used a model of clonic seizure induced by pentylenetetrazole (PTZ) in male NMRI mice to investigate whether the anticonvulsant effect of lithium is mediated via NO-cGMP pathway. Injection of a single effective dose of lithium chloride (25 mg/kg) intraperitoneally (i.p.) increased significantly the seizure threshold (P<0.01). The anticonvulsant properties of the effective dose of lithium were prevented by pre-treatment with the per se non-effective doses of L-ARG [the substrate for nitric oxide synthase; NOS] (30 and 50 mg/kg) or sildenafil [a phosphodiesterase 5 inhibitor] (10 and 20 mg/kg). L-NAME [a non-specific NOS inhibitor] (5, 15 and 30 mg/kg), 7-NI [a specific neural NOS inhibitor] (30 and 60 mg/kg) or MB [a guanylyl cyclase inhibitor] (0.5 and 1 mg/kg) augmented the anticonvulsant effect of a sub-effective dose of lithium (10 mg/kg, i.p.). Whereas several doses of aminoguanidine [an inducible NOS inhibitor] (20, 50 and 100 mg/kg) failed to alter the anticonvulsant effect of lithium. Our findings demonstrated that nitric oxide-cyclic GMP pathway could be involved in the anticonvulsant properties of the lithium chloride. In addition, the role of constitutive NOS versus inducible NOS is prominent in this phenomenon. PMID- 20304612 TI - Charged layer with undulated surface: configuration of electrical double layer. AB - A charged layer with undulated surface exists commonly in natural entities (for example the biological membrane layer and the surface of charged colloid) and in artificial fabrications (for example the peripheral surface of ion-exchange membrane pores). When the micro- or nano-scale charged layer systems are concerned, the effect of undulation of charged layer surface on the electrical phenomenon may become great significant. In this work, using the perturbation method, the significance of undulated surface on a charged layer in the electrical phenomenon is investigated. Under assumptions that the undulation amplitude is small and that the Debye-Huckel approximation is applicable, the electrical potential field in three regions is solved simultaneously. Based on the analytical results it is found that, if compared with that in condition of flat surface, the undulation of charged layer surface decreases/increases the magnitude of electrical potential field near the wave crest/trough, due to the curvature of undulated surface. In addition, the surface potential on the undulated surface shows a wavelike distribution. The analytical results also show that, the significance of undulated surface is determined by the physical parameters, including the geometry of undulated surface, the amplitude and the period of undulation, and the fixed charge density in charged layer. PMID- 20304613 TI - Use of insulin detemir during pregnancy. PMID- 20304614 TI - The influence of the S19W SNP of the APOA5 gene on triglyceride levels in southern Brazil: interactions with the APOE gene, sex and menopause status. AB - BACKGROUND AND AIMS: Hypertriglyceridemia is an important independent risk factor for coronary artery diseases and is determined by a wide range of factors, both genetic and exogenous. The A5 apolipoprotein, which is associated with the synthesis and removal of triglycerides (TG), is encoded by the APOA5 gene. One of the polymorphisms of this gene that has been the focus of a large number of studies, and which appears to be associated with increased TG, is S19W (rs 3135506). In this study, we examined the influence of this single nucleotide polymorphism (SNP) on TG levels of a sample of southern Brazilians. METHODS AND RESULTS: Samples obtained from 567 people of European descent were genotyped; interactions between this variant and anthropometric variables were analyzed, and the effects of lifestyle, sex, menopause, and variations of the APOE gene were evaluated. We found that the 19W allele is associated with increased TG (p = 0.025) and that this influence was modulated by sex (p = 0.003), menopause (p = 0.022) and the presence of the E*4 allele (p = 0.027). CONCLUSION: Our data showed, for the first time, the importance and magnitude of the influence of the S19W variant in a southern Brazilian population. PMID- 20304615 TI - -94 ins/del ATTG NFKB1 gene variant is associated with lower susceptibility to myocardial infarction. AB - BACKGROUND AND AIMS: An imbalance of Nuclear Factor Kappa B (NFkB) and Inhibitor Kappa B (IkB) is involved in various human diseases including atherogenesis. We aimed to evaluate the relationship between NFKB1 and NFKBIA polymorphism and susceptibility to myocardial infarction (MI). METHODS AND RESULTS: Genotyping was performed for NFKB1 and NFKBIA gene variants in 253 subjects (86 patients affected by myocardial infarction and 167 control subjects). In 40 patients, biopsy specimens were taken from the left ventricle area of presumed ischemia for p50, p65 and IkBalpha quantification. The allele frequency and genotype distribution of NFKBIA gene polymorphism did not differ between MI and control group while control subjects had a higher D allele frequency of -94 ins/del ATTG NFKB1 polymorphism, compared to the MI group (P<0.001; OR=0.304; 95% CI=0.177 0.522). Subjects carrying the D allele had significantly lower plasma fibrinogen and CRP (C-reactive protein) levels compared to no carriers (P<0.05). Fibrinogen genotype interaction was found to have a significant effect on susceptibility to myocardial infarction. Myocardial p50 (r=0.627; P=0.012) and p65 (r=0.683; P=0.005) levels significantly correlated with plasma fibrinogen levels while subjects carrying the D allele of the NFkB1 gene variant had lower myocardial p50 (P=0.007) and p65 (P=0.009) levels compared to no carriers. CONCLUSION: -94 ins/del ATTG NFKB1 gene variant may contribute to lower MI susceptibility via the potential reduction of activated NFkB which in turn is related to plasma inflammatory marker reduction. PMID- 20304616 TI - The G3057A LEPR polymorphism is associated with obesity in Tunisian women. AB - OBJECTIVES: The aim of this study was to evaluate the effect of the G3057A (rs62589000) LEPR polymorphism on obesity risk and plasma leptin, insulin, and lipid levels in a sample of the Tunisian population. DESIGN AND METHODS: Three hundred and ninety-three obese patients and 317 controls participated in this study. The G3057A genotype was determined by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) analysis. RESULTS: In the entire study sample, no significant differences in genotype frequencies were observed between obese patients and controls. However, stratified analysis by gender revealed a quantitative increase in the variant allele (33.3% vs. 25.8%; chi(2)=4.90, p=0.026) in obese women (but not men) compared to controls. When a dominant model of inheritance was assumed, the GA+AA genotypes were more prevalent in these obese female patients than in controls (58.3% vs. 47.8%; chi(2)=4.08, p=0.044). Unconditional logistic regression showed that in women only, obesity risk was significantly higher for homozygotes for the variant allele (OR=2.73, 95% CI 1.03-7.21) and for carriers of GA+AA genotypes (OR=1.53, 95% CI 1.01-2.31) compared with homozygotes for the normal allele. The association between the G3057A LEPR variant and obesity remained statistically significant even after adjustment for age. No relationship was found between the G3057A LEPR polymorphism and leptin and insulin levels. Additionally, this LEPR gene variant had no effect on plasma lipid concentrations. CONCLUSION: There is evidence in this study that the G3057A LEPR polymorphism is associated with obesity in Tunisian women. PMID- 20304617 TI - Adiposity indices in the prediction of metabolic abnormalities associated with cardiovascular disease in non-diabetic adults. AB - BACKGROUND AND AIMS: The prevalence of insulin resistance and cardiovascular disease (CVD) increases with degree of obesity. Whether measurements of generalized and abdominal obesity differ in the ability to predict changes associated with increased CVD risk is widely debated. We compared the prevalence of metabolic abnormalities in 275 women and 204 men stratified by categories of body mass index (BMI) and waist circumference (WC), and assessed the ability of these adiposity indices in combination with metabolic risk variables to predict insulin resistance. METHODS AND RESULTS: Healthy, non-diabetic volunteers underwent measurements of BMI, WC, blood pressure, fasting plasma glucose (FPG), lipoprotein concentrations, and direct quantification of insulin-mediated glucose uptake. Insulin resistance was defined as the top tertile of steady-state plasma glucose (SSPG) concentrations. BMI and WC were highly correlated (P < 0.001) in both women and men. Abnormal SSPG and triglyceride concentrations were associated with increasing adiposity by either index in both genders. Among women, abnormal FPG and high density lipoprotein cholesterol (HDL-C) concentrations were associated with increasing BMI and WC. In men, abnormal HDL-C was associated with increasing BMI only. Elevated systolic blood pressure (SBP) was associated with increasing BMI in both genders. The odds of insulin resistance were greatest in women with elevated FPG and triglycerides (4.5-fold). In men, the best predictors were BMI and SBP, and WC and HDL-C (3-fold). CONCLUSION: BMI is at least comparable to WC in stratifying individuals for prevalence of metabolic abnormalities associated with increased CVD risk and predicting insulin resistance. PMID- 20304618 TI - Differential effects of endothelins on histological and ultrastructural changes and trypsinogen activation in the secretagogue-induced acute pancreatitis in rats. AB - The role of endothelins in acute pancreatitis remains obscure. To assess the effects of endothelins (ETs) in early (4 h) caerulein-induced acute pancreatitis (AP) in rats, ET-1, ET-2 and ET-3 (0.5 or 1.0 nmol/kg) were applied twice with i.p. caerulein (2*40 MUg/kg) at 1h interval. Histological and ultrastructural examinations of pancreases and the assay of trypsinogen activation in whole homogenate were performed. All ETs, especially ET-1 at the higher dose, decreased inflammatory cell infiltration despite an increase in the edema score. The vacuolization and necrosis of acinar cells were slightly increased after the lower dose of ET-1 and ET-2. Ultrastructural changes were generally improved after the higher dose of ETs. Trypsinogen activation increased from 4.8+/-1.3% in control to 18.4+/-3.8% in AP (p<0.01). It was attenuated to 6.4+/-1.3% (p<0.01) by the higher dose of ET-1 and to 8.8+/-1.5% (p<0.05) by the lower dose of ET-3. In summary, ETs, especially ET-1 at the higher dose, were found to have some beneficial effects on morphological changes and trypsinogen activation in the pancreas in early caerulein-induced AP. PMID- 20304619 TI - The involvement of ROS overproduction and mitochondrial dysfunction in PBDE-47 induced apoptosis on Jurkat cells. AB - 2,2',4,4'-Tetrabromodiphenyl ether (PBDE-47), as one of the congeners of polybrominated diphenyl ethers (PBDEs), is widely present and threatens the human health in many aspects. This study aims to investigate the toxic effects of PBDE 47 on cell viability, apoptosis, reactive oxygen species (ROS) and mitochondrial membrane potential (MMP) of Jurkat cells in vitro. The results showed that PBDE 47 significantly inhibited the viability of Jurkat cells in a dose-dependent manner by alamar blue assay. Significant induction of apoptosis was detected in Jurkat cells at 25-100 MUM by propidium iodide staining, accompanied with overproduction of ROS and downregulation of MMP. Furthermore, N-acetyl-L-cysteine (NAC), a widely used ROS scavenger, significantly reduced the PBDE-47-induced apoptosis by decreasing ROS level and mediating recovery of the MMP. In conclusion, the results of this study suggest that PBDE-47 could induce apoptosis in Jurkat cells and ROS and mitochondrial dysfunction play important roles in the apoptotic process. PMID- 20304620 TI - Effect of fluoride on calcium ion concentration and expression of nuclear transcription factor kappa-B rho65 in rat hippocampus. AB - The study investigated the neurotoxicity of drinking water fluorosis in rat hippocampus. Just weaning male Sprague-Dawley (SD) rats were given 15, 30, 60 mg/L NaF solution and tap water for 9 months. The calcium ion concentration ([Ca(2+)]) in synaptosomes was measured by double wavelength fluorescence spectrophotometer and the expression level of nuclear transcription factor kappa B rho65 (NF-kappaB rho65) in hippocampal CA3 region was measured by immunohistochemistry. The results showed that [Ca(2+)] significantly increased (F = 33.218, P < 0.01) in moderate fluoride group compared with the control group, and the expression level of NF-kappaB rho65 in CA3 region presented an increasing trend as fluoride concentration increased. These results indicate that increase of synaptosomes [Ca(2+)] and NF-kappaB rho65 expression level may be the molecular basis of central nervous system damage caused by chronic fluoride intoxication. NF-kappaB rho65 in CA3 region is probably a target molecule for fluorosis. PMID- 20304621 TI - Technical evolution of landfilling. PMID- 20304622 TI - Steady-state design of vertical wells for liquids addition at bioreactor landfills. AB - The rate at which liquids can be added to a vertical well, the lateral zone of impact of the well, and the liquids volume needed to wet the waste within the zone of impact of the well are the key inputs needed to design a vertical well system. This paper presents design charts that can be used to estimate these inputs as a function of municipal solid waste properties (porosity, hydraulic conductivity, and anisotropy ratio), well dimensions (radius and screen length), and injection pressure. SEEP/W modeling was conducted to estimate the key design inputs for a range of conditions practically encountered for a vertical well installed in landfilled waste. The flow rate, lateral zone of impact of a well, liquids volume added, and injection pressure were normalized with the waste properties and well dimensions to formulate dimensionless variables. A series of design charts were created to present dimensionless steady-state flow rate, lateral zone of impact, and the dimensionless liquid volume needed to reach a steady-state condition, as a function of dimensionless input variables. By using dimensionless variables formulated for this work, these charts permit the user to estimate the steady-state design variables described above for a wide range of configurations and conditions beyond those simulated without the need for further modeling. The results of the study suggest that the lateral extent of the well can be estimated using Darcy's equation and assuming saturated unit-gradient vertical flow regime below the well bottom. An example problem is presented to illustrate the use of the design charts. The scenario described in the example problem was also modeled with SEEP/W, and the results were compared with those obtained from the design charts to demonstrate the validity of design charts for scenarios other than those used for the development of the design charts. The methodology presented in this paper should be thought of as a means to provide a set of bounds that an engineer can use along with their judgment in the design of a system for a specific site. PMID- 20304623 TI - A steady-state approach for evaluating the impact of solute transport through composite liners on groundwater quality. AB - New adaptations of analytical equations for predicting the impact of solute transport through composite landfill liners on groundwater quality for steady state conditions are presented. Analytical equations are developed for evaluating average concentration and mass flow rate in an underlying aquifer resulting from diffusion of volatile organic compounds (VOCs) through intact composite liners and transport of inorganic constituents through defects in composite liners. The equations are applied to evaluate the effectiveness and equivalency of composite liners having either a 0.6 m-thick compacted soil liner or a 6.5 mm-thick geosynthetic clay liner (GCL) overlying an intermediate attenuation layer and an aquifer having horizontal flow. Example analyses for designing composite liners meeting particular performance criteria are also provided. The analytical equations are relatively simple to apply and can be used for preliminary design and analysis, to evaluate experimental results, and to possibly verify more complex numerical models for evaluating the impact of landfills on groundwater quality if consistency of the assumptions of the analytical equations and the more complex numerical models can be specified. PMID- 20304624 TI - Real-time electrical impedance detection of cellular activities of oral cancer cells. AB - In this study, the electric cell-substrate impedance sensing (ECIS) system was used to study the cellular activities of oral squamous cell carcinoma (OSCC) cells in a real-time and label-free manner. Various cellular activities, including cell adhesion, spreading, proliferation, and drug-induced apoptosis and inhibition of apoptosis, were monitored. A linear relationship was found between the impedance-based cell index and the cell number in the range of 3500 to 35,000 cells/well. Anti-cancer drug-cisplatin-induced OSCC cell apoptosis at the minimal concentration of 5 microM after 20 h of treatment and followed a linear dose dependent manner in the concentration range from 10 microM to 25 microM. The inhibition of cisplatin-induced apoptosis by the carcinogen, nicotine, at concentrations from 0.1 microM to 10 microM was monitored. The most significant inhibitory effect of nicotine on cisplatin-induced apoptosis was observed at concentrations of 0.5-1 microM. The results obtained with impedance method correlated well with microscopic imaging analysis of cellular morphology and cell viability analysis. This study demonstrated that the impedance-based method can provide real-time information about the cellular activity of viable cells and detect drug-induced cellular activities much earlier than commonly used cell based image analysis. This impedance-based method has the potential to provide a useful analytical approach for cancer research. PMID- 20304625 TI - Warburg tumours and the mechanisms of mitochondrial tumour suppressor genes. Barking up the right tree? AB - The past decade has seen a revival of interest in the metabolic adaptations of tumours, named for their original discoverer, Otto Warburg. Warburg reported a high rate of glycolysis in tumours, and a concurrent defect in mitochondrial respiration. The rediscovery of Warburg's hypothesis coincided with the discovery of mitochondrial tumours suppressor genes that may conform to Warburg's hypothesis. Succinate dehydrogenase and fumarate hydratase are mitochondrial proteins of the TCA cycle and the respiratory chain and when mutated lead to tumours of the nervous system known as paragangliomas and pheochromocytomas, and in the case of fumarate hydratase, cutaneous and uterine leiomyomas and renal cell cancer. Recently a novel mitochondrial protein, SDHAF2 (SDH5), was also shown to be a paraganglioma-related tumour suppressor gene. Another mitochondrial and TCA cycle-related protein, isocitrate dehydrogenase 2 is, together with IDH1, frequently mutated in the brain tumour glioblastoma. There are currently many competing hypotheses on the role of these genes in tumourigenesis, but frequent themes are the stabilization of hypoxia inducible factor 1 and upregulation of genes involved in angiogenesis, glucose transport and glycolysis. Other postulated mechanisms include the inhibition of developmental apoptosis, altered gene expression due to histone deregulation and the acquisition of novel catalytic properties. Here we discuss these diverse hypotheses and highlight very recent findings on the possible effects of IDH gene mutations. PMID- 20304626 TI - The Nm23-H1 metastasis suppressor as a translational target. AB - Nm23 was the first of what has become a field of over 20 known metastasis suppressor genes (MSGs). Since the discovery of Nm23 in 1988, a variety of mechanisms have been attributed to its activity, including a histidine kinase activity, binding of other proteins to regulate metastatic formation, and altered gene expression downstream of Nm23. Here, we will review current efforts to translate the previous work done on this MSG into the clinic, including high-dose medroxyprogesterone acetate (MPA), which has been shown to upregulate Nm23 expression. In addition, we will detail a new potential target downstream of Nm23. LPA1 is one of a group of known cell surface receptors for lysophosphatidic acid (LPA), which has been shown to be inversely correlated with Nm23 expression. A specific LPA1 antagonist could conceivably mimic the effects of Nm23 by downregulating the activity of the LPA1 pathway, which would be of considerable interest for potential clinical use. PMID- 20304627 TI - Prognostic value of microsatellite instability (MSI) and PTEN expression in women with endometrial cancer: results from studies of the NCIC Clinical Trials Group (NCIC CTG). AB - AIM: The impact of PTEN status and microsatellite instability (MSI) on the prognosis of women with endometrial cancer is controversial. The aim of this study was to investigate MSI and PTEN expression in two patient populations using data from NCIC CTG studies. METHODS: Archival paraffin embedded tumour from women with endometrial cancer enrolled in NCIC CTG studies: EN5 (stage I/II) and IND 126, 148 and 160 (advanced/recurrent disease) were examined for MSI using BAT25/26 and for PTEN expression using immunohistochemistry. PTEN and MSI status were correlated with clinicopathologic variables and survival using data from NCIC CTG trial databases. RESULTS: PTEN and MSI results were available from 128 and 163 patients, respectively. MSI+ tumours were more common in women enrolled in EN5 compared to the IND studies (p=0.01). PTEN negative tumours were associated with improved survival in both univariate (hazard ratio (HR) 0.55, 95% confidence interval (CI) 0.32-0.94; p=0.03) and multivariate (adjusted HR 0.54, 95% CI 0.30-0.96; p=0.03) analyses in women enrolled in IND studies. Microsatellite stable tumours were associated with an improved prognosis in univariate (HR 0.18, 95% CI 0.06-0.51; p<0.0001) and multivariate (adjusted HR 0.16, 95% CI 0.05-0.5; p<0.0001) analyses in women enrolled in EN5. There was no significant correlation between MSI and PTEN status. CONCLUSIONS: PTEN negative tumours in women with advanced disease are associated with improved survival. MSI+ tumours are more common in early stage disease and in this group of women are associated with a worse prognosis. PMID- 20304628 TI - Phase II trial of the histone deacetylase inhibitor belinostat in women with platinum resistant epithelial ovarian cancer and micropapillary (LMP) ovarian tumours. AB - AIM: Micropapillary/borderline (LMP) ovarian tumours are rarely included in clinical trials and are intrinsically resistant to radiation and chemotherapy. Platinum resistant epithelial ovarian cancer (EOC) has a poor prognosis. The histone deacetylase inhibitor belinostat demonstrated antitumour activity in pre clinical ovarian cancer models. METHODS: A phase II study was performed to evaluate the activity of belinostat in two patient populations: women with metastatic or recurrent platinum resistant (progression within 6 months) EOC and LMP ovarian tumours, both groups had received no more than 3 prior lines of chemotherapy. Belinostat 1000 mg/m(2)/d was administered iv days 1-5 of a 21 d cycle. Peripheral blood mononuclear cells (PBMCs) and tumour biopsies, where possible, for correlative studies were obtained prior to and following treatment. RESULTS: Eighteen patients with EOC and 14 patients with LMP tumours were enrolled on study. Belinostat was well tolerated with no grade four toxicity (179 cycles). Grade 3 toxicity consisted of thrombosis (3 patients), hypersensitivity (1) and elevated ALP (1). One patient with LMP tumour had a partial response (unconfirmed) and 10 had stable disease (SD), 3 were non-evaluable. Median progression-free survival (PFS) was 13.4 months (95% confidence interval (CI), 5.6--not reached). Best response in patients with EOC was SD (nine patients) and median PFS was 2.3 months (95% CI, 1.2-5.7 months). An accumulation of acetylated histones H3 and H4 was noted in PBMCs and in tumour tissue. CONCLUSIONS: Belinostat is well tolerated in both patient groups and shows some activity in patients with micropapillary (LMP) disease. PMID- 20304629 TI - Magnetic resonance imaging of the breast: recommendations from the EUSOMA working group. AB - The use of breast magnetic resonance imaging (MRI) is rapidly increasing. EUSOMA organised a workshop in Milan on 20-21st October 2008 to evaluate the evidence currently available on clinical value and indications for breast MRI. Twenty three experts from the disciplines involved in breast disease management - including epidemiologists, geneticists, oncologists, radiologists, radiation oncologists, and surgeons - discussed the evidence for the use of this technology in plenary and focused sessions. This paper presents the consensus reached by this working group. General recommendations, technical requirements, methodology, and interpretation were firstly considered. For the following ten indications, an overview of the evidence, a list of recommendations, and a number of research issues were defined: staging before treatment planning; screening of high-risk women; evaluation of response to neoadjuvant chemotherapy; patients with breast augmentation or reconstruction; occult primary breast cancer; breast cancer recurrence; nipple discharge; characterisation of equivocal findings at conventional imaging; inflammatory breast cancer; and male breast. The working group strongly suggests that all breast cancer specialists cooperate for an optimal clinical use of this emerging technology and for future research, focusing on patient outcome as primary end-point. PMID- 20304631 TI - Effect of heat-shock treatment on the survival of Escherichia coli O157:H7 and Salmonellaenterica Typhimurium in dairy manure co-composted with vegetable wastes under field conditions. AB - This study investigated the survival of heat-shocked (HS) and non-heat-shocked (NHS) Escherichia coli O157:H7 and Salmonellaenterica Typhimurium when co composting dairy manure and vegetable wastes in a field setting. In the summer, HS E. coli O157:H7 and Salmonella survived for 7 and 2 days longer at the surface and bottom locations of the compost heaps, respectively, than NHS cultures. Both HS and NHS E. coli O157:H7 and Salmonella were detectable in all compost samples for more than 60 days in the winter. The results indicate that composting dairy manure with vegetable wastes under sub-optimal conditions may allow extended survival of pathogens in the heap at low ambient temperature. Analysis of covariance revealed that the heat-shock treatment may have induced cross resistance to desiccation, allowing extended survival of HS E. coli O157:H7 and Salmonella at the surface of the compost heaps during the summer. PMID- 20304630 TI - Extracellular matrix: a gatekeeper in the transition from dormancy to metastatic growth. AB - Metastases can develop after apparently successful treatment of a primary tumour, sometimes following a period of tumour dormancy that can last for years. However, factors that regulate metastatic tumour dormancy remain poorly understood. Here we review the potential contribution of interactions between tumour cells and the microenvironment in metastatic sites, in regulating tumour dormancy vs. metastatic growth. We focus particularly on the potential role of the extracellular matrix (ECM) in regulating maintenance and release from dormancy. Tumour cells that fail to properly adhere to the ECM may enter a state of dormancy. The molecular and physical composition of the ECM can be affected by tumour cells themselves, as well as multiple stromal cell types. The roles of integrins, fibronectin, and collagen are discussed, as are factors that can change the ECM. A better understanding of the molecular details of the crosstalk between tumour cells and the ECM in secondary sites, and how these regulate the dormant state, may lead to improved therapeutic strategies to induce or maintain disseminated tumour cells in a dormant state, or alternatively to successfully eradicate dormant cells. PMID- 20304632 TI - Biochemical characterization of a maize stover beta-exoglucanase and its use in lignocellulose conversion. AB - Plant is one of the important resources for glycosyl hydrolase production. A beta exoglucanase with molecular weight of 63.1 kDa was purified from fresh maize stover and subjected to enzymatic characterization. The optimal temperature and pH of the beta-exoglucanase was 40 degrees C and 6.0, respectively. The beta exoglucanase was active against p-nitrophenyl-cellobiose (p-NPC), laminarin, cellotriose, cellotetraose, cellopentaose, Avicel, filter paper, and cotton cellulose. The analysis of hydrolytic mode suggested that the beta-exoglucanase removed cellobiose from the ends of beta-glucan. Kinetic parameters of the beta exoglucanase for laminarin and p-NPC were determined. The effects of metal ions and chemical reagents on the beta-exoglucanase activity were also studied. The biochemical characterization of the beta-exoglucanase makes it an appealing cellulase additive in converting lignocelluloses to ethanol through simultaneous saccharification and fermentation. The synergism of the beta-exoglucanase or crude cell wall proteins of fresh maize stover with Trichoderma reesei cellulase was observed in ethanol production from lignocellulose. PMID- 20304633 TI - Glycerol acetals as anti-freezing additives for biodiesel. AB - Glycerol acetals from butanal, pentanal, hexanal, octanal and decanal were prepared with the use of Amberlyst-15 acid resin as catalyst. The glycerol conversion decreases with the size of the hydrocarbon chain. This fact has been associated with formation of micelles and aggregates of the aldehyde to minimize the interaction between the polar glycerol molecule with the hydrocarbon chain. The Z+E mixture of the acetals with five and six-member rings were produced in all cases. The distribution of the acetal isomers varied with the reaction time, especially for the long chain aldehydes. Addition of 5 vol.% of the butanal glycerol acetal reduced the pour point of animal fat biodiesel (methyl ester) from 18 to 13 degrees C. The decrease in the pour point of the glycerol acetals biodiesel mixtures were dependent on the size of the hydrocarbon chain and the percent blended. PMID- 20304634 TI - Separation of ethanol/water azeotrope using compound starch-based adsorbents. AB - Comparing breakthrough cures of five starch-based materials experimentally prepared for ethanol dehydration, a compound adsorptive agent ZSG-1 was formulated with high adsorption capacity, low energy and material cost. The selective water adsorption was conducted in a fixed-bed absorber packed with ZSG 1 to find the optimum conditions yielding 99.7 wt% anhydrous ethanol with high efficiency. The adsorption kinetics is well described by Bohart-Adams equation. The adsorption heat, Delta H(abs), was calculated to be -3.16 x 10(4)J mol(-1) from retention data by inverse gas chromatography. Results suggested that water entrapment in ZSG-1 is a exothermic and physisorption process. Also, ZSG-1 is recyclable for on-site multiple-use and then adapt for upstream fermentation process after saturation, avoiding pollution through disposal. PMID- 20304635 TI - Effect of vitamin B12 pulse addition on the performance of cobalt deprived anaerobic granular sludge bioreactors. AB - The effect of a pulse addition of vitamin B(12) as cobalt source to restore the performance of cobalt depleted methanol-fed bioreactors was investigated. One upflow anaerobic sludge bed (UASB) reactor was supplied with a pulse of vitamin B(12), and its operation was compared to that of another cobalt depleted UASB reactor to which a pulse of CoCl(2) was given. The addition of cobalt in the form of CoCl(2) supplies enough cobalt to restore methanogenesis and maintain full methanol degradation coupled to methane production during more than 35 days after the CoCl(2) pulse. Similar to CoCl(2), pulse addition of vitamin B(12) supplies enough cobalt to maintain full methanol degradation during more than 35 days after the pulse. However, the specific methanogenic activities (SMAs) of the sludge in the vitamin B(12) supplied reactor were around 3 times higher than the SMA of the sludge from the CoCl(2) supplied reactor at the same sampling times. An appropriate dosing strategy (repeated pulse dosing) combined with the choice of vitamin B(12) as the cobalt species is suggested as a promising dosing strategy for methanol-fed anaerobic bioreactors limited by the micronutrient cobalt. PMID- 20304636 TI - Modeling of reaction kinetics for transesterification of palm-based methyl esters with trimethylolpropane. AB - A mathematical model describing chemical kinetics of transesterification of palm based methyl esters with trimethylolpropane has been developed. The model was developed by utilizing nonlinear regression method, which is an efficient and powerful way to determine rate constants for both forward and reverse reactions. A comparison with previous study which excludes the reverse reactions was made. The model was based on the reverse mechanism of transesterification reactions and describes concentration changes of trimethylolpropane, monoesters and diesters production. The developed model was validated against data from the literature. The reaction rate constants were determined using MATLAB version 7.2 and the ratios of rate constants obtained were well in agreement with those reported in the literature. A good correlation between model simulations and experimental data was observed. It was proven that both methods were able to predict the rate constants with plausible accuracy. PMID- 20304637 TI - Impact of surfactants on pretreatment of corn stover. AB - Lignin in pretreated cellulosic biomass can non-productively adsorb cellulase, resulting in loss of a significant portion of this expensive protein. In addition, lignin interferes with the path for cellulase action, slowing down hydrolysis. Thus, the effectiveness of enzymatic hydrolysis of pretreated lignocellulosic biomass can be significantly enhanced if lignin is removed or effectively modified before adding enzymes. In this study, the enzymatic digestibilities of solids resulting from using the surfactants Tween-80, dodecylbenzene sulfonic acid, and polyethylene glycol 4000 during water-only or dilute acid pretreatment of corn stover at 140-220 degrees C were evaluated. All of these surfactants increased lignin removal during pretreatment and reduced non productive binding of enzymes on the biomass surface, but Tween-80 increased enzymatic hydrolysis yields and enhanced total sugar recovery more than the other two. Surfactant pretreatment was found to improve lignin solubility, which could improve cellulose digestibility by reducing unproductive binding to enzyme, and also appeared to enhance performance by modifying the biomass surface. PMID- 20304638 TI - Phosphorus and zinc dissolution from thermally gasified piggery waste ash using sulphuric acid. AB - Ash from thermally gasified piggery waste (GA) was treated with sulphuric acid (H(2)SO(4)) using two extraction methods. First different loads (0.39-0.98 kg H(2)SO(4)/kg ash) and concentrations (0.2-2M) were used in 3h extraction. Second, titration of 1:25 (w/w) ash:water suspension was conducted with 4M H(2)SO(4) to determine ash buffer capacity at nine pH steps from 12 to 0.1. Total P and zinc (Zn) dissolution was monitored. Optimal acid load and concentration to dissolve 94% P and 55% Zn from GA was 0.98 kg H(2)SO(4)/kg ash and 0.6M, respectively, which corresponds to acid demand of 19.2 kg H(2)SO(4)/kg P recovered. High concentrations (2M) did not improve P dissolution, but Zn was easier released. Ash buffer capacity was the highest at pH 4 and 0.1, first one due to dissolution of Ca, the second one due to autoprotolysis of water. Acid load had stronger effect on dissolution than concentration in the first method, however in the second; both factors had comparable effect. PMID- 20304639 TI - Exploration of amino alcohol derivatives as novel, potent, and highly selective sphingosine-1-phosphate receptor subtype-1 agonists. AB - In pursuit of a potent and highly selective sphingosine-1-phosphate receptor agonists with an improved in vivo conversion of the precursor to the active phospho-drug, we have utilized previously reported phenylamide and phenylimidazole scaffolds to identify a selectivity enhancing moiety (SEM) and selectivity enhancing orientation (SEO) within both pharmacophores. SEM and SEO have allowed for over 100 to 500-fold improvement in selectivity for S1P receptor subtype 1 over subtype 3. Utility of SEM and SEO and further SAR study allowed for discovery of a potent and selective preclinical candidate PPI-4955 (21b) with an excellent in vivo potency and dose responsiveness and markedly improved overall in vivo pharmacodynamic properties upon oral administration. PMID- 20304640 TI - Synthesis and characterization of a Eu-DTPA-PEGO-MSH(4) derivative for evaluation of binding of multivalent molecules to melanocortin receptors. AB - A labeled variant of MSH(4), a tetrapeptide that binds to the human melanocortin 4 receptor (hMC4R) with low microM affinity, was prepared by solid-phase synthesis methods, purified, and characterized. The labeled ligand, Eu-DTPA-PEGO His-dPhe-Arg-Trp-NH(2), exhibited a K(d) for hMC4R of 9.1+/-1.4 microM, approximately 10-fold lower affinity than the parental ligand. The labeled MSH(4) derivative was employed in a competitive binding assay to characterize the interactions of hMC4R with monovalent and divalent MSH(4) constructs derived from squalene. The results were compared with results from a similar assay that employed a more potent labeled ligand, Eu-DTPA-NDP-alpha-MSH. While results from the latter assay reflected only statistical effects, results from the former assay reflected a mixture of statistical, proximity, and/or cooperative binding effects. PMID- 20304641 TI - Eastern extension of azoles as non-nucleoside inhibitors of HIV-1 reverse transcriptase; cyano group alternatives. AB - Design of non-nucleoside inhibitors of HIV-1 reverse transcriptase is being pursued with the assistance of free energy perturbation (FEP) calculations to predict relative free energies of binding. Extension of azole-containing inhibitors into an 'eastern' channel between Phe227 and Pro236 has led to the discovery of potent and structurally novel derivatives. PMID- 20304642 TI - Discovery of triarylethanolamine inhibitors of the Kv1.5 potassium channel. AB - A series of triarylethanolamine inhibitors of the Kv1.5 potassium channel have been prepared and evaluated for their effects in vitro and in vivo. The structure activity relationship (SAR) studies described herein led to the development of potent, selective and orally active inhibitors of Kv1.5. PMID- 20304643 TI - Enhanced Nrf2-dependent induction of glutathione in mouse embryonic fibroblasts by isoselenocyanate analog of sulforaphane. AB - Epidemiological and laboratory studies have highlighted the potent chemopreventive effectiveness of both dietary selenium and cruciferous vegetables, particularly broccoli. Sulforaphane (SFN), an isothiocyanate, was identified as the major metabolite of broccoli responsible for its anti-cancer properties. An important mechanism for SFN chemoprevention is through the enhancement of glutathione (GSH), the most abundant antioxidant in animals and an important target in chemoprevention. Enhancement of GSH biosynthetic enzymes including the rate-limiting glutamate cysteine ligase (GCL), as well as other Phase II detoxification enzymes results from SFN-mediated induction of the nuclear factor-erythroid 2-related factor 2 (Nrf2)/antioxidant response elements (ARE) signaling pathway. While isothiocyanate compounds such as SFN are among the most potent Nrf2 inducers known, we hypothesized that substitution of sulfur with selenium in the isothiocyanate functional group of SFN would result in an isoselenocyanate compound (SFN-isoSe) with enhanced Nrf2 induction capability. Here we report that SFN-isoSe activated an ARE-luciferase reporter in HepG2 cells more potently than SFN. It was also found that SFN-isoSe induced GCL and GSH in MEF cells in an Nrf2-dependent manner. Finally, we provide evidence that SFN isoSe was more effective in killing HepG2 cancer cells, yet was less toxic to non cancer MEF cells, than SFN. These data support our hypothesis, and suggest that SFN-isoSe and potentially other isoselenocyanates may be highly effective chemoprotective agents in vivo due to their ability to induce Nrf2 with low toxicity in normal cells and high efficiency at killing cancer cells. PMID- 20304644 TI - N-aryltriazole ribonucleosides with potent antiproliferative activity against drug-resistant pancreatic cancer. AB - Novel N-aryltriazole nucleosides were synthesized via Cu-mediated C-N cross coupling reaction starting with 3-aminotriazole ribonucleoside and various boronic acids. Two of them exhibited potent apoptosis-related antiproliferative activity against the drug-resistant pancreatic cancer cell line MiaPaCa-2, with an increased potency compared to gemcitabine, the reference treatment for pancreatic cancer. A preliminary SAR study suggests that the appended N-aryl moiety and the substituent at its para-position, as well as the ribose sugar component, contribute considerably to the observed antiproliferative activity. PMID- 20304645 TI - Substituted hydrazinecarbothioamide as potent antitubercular agents: synthesis and quantitative structure-activity relationship (QSAR). AB - A series of novel substituted hydrazinecarbothioamides was synthesized and evaluated for anti-TB activity. Three most active compounds viz. 1, 6 and 12 were found to exhibit minimum inhibitory concentration (MIC) of 0.4 microg/mL, whereas four compounds viz. 3, 5, 10 and 11 showed comparatively lesser activity with MIC value of 0.8 microg/mL against Mycobacterium tuberculosis strain. A highly significant QSAR equation explaining 81.8% variance is described. PMID- 20304646 TI - WITHDRAWN: Nemaline myopathy presenting as a stiff baby. AB - This article has been withdrawn at the request of the author and editor. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at http://www.elsevier.com/locate/withdrawalpolicy. PMID- 20304647 TI - Reverse protein arrays as novel approach for protein quantification in muscular dystrophies. AB - The definite molecular diagnosis in patients with muscular dystrophies often requires the assessment of muscular expression of multiple proteins in small amounts of muscle tissue. The sample material obtained in muscle biopsies is limited and the measurement of multiple proteins is often restricted to conventional, non-quantitative assays, i.e. immunohistochemistry and immunoblotting. Here, we demonstrate that reverse protein arrays are a novel and excellent material-saving method for the measurement and quantification of changes in protein expression between healthy and diseased muscle tissue as well as cultured primary myotubes. We evaluated a set of antibodies and found reproducible differences between Duchenne muscular dystrophy/limb-girdle muscular dystrophy patients and control samples for dystrophin, the sarcoglycans and the dystroglycans. As little as 10 mg of tissue is sufficient for the analysis of all diagnostically relevant proteins. The average coefficient of variation calculated for the sample signals confirmed that the method is highly reproducible. Thus, our experiments provide strong evidence that quantitative protein detection from very small amounts of muscle tissue is possible using reverse protein arrays. This technology may not only be of interest for diagnostic purposes, but also for protein quantification of multiple, follow-up biopsies during clinical trials when protein expression in muscle is considered an important outcome measure or biomarker. PMID- 20304648 TI - Improved muscle strength and mobility in the dy(2J)/dy(2J) mouse with merosin deficient congenital muscular dystrophy treated with Glatiramer acetate. AB - The therapeutic effect of Glatiramer acetate, an immune modulating agent, was evaluated in the dy(2J)/dy(2J) mouse with merosin deficient congenital muscular dystrophy, which is a milder variant of the dy/dy mouse. The treated mice showed significant improvement in hind limb muscle strength measured by electronic grip strength meter and in motor performance quantified by video detection software. Glatiramer acetate treatment was associated with significantly increased expression of regeneration transcription factors MyoD and myogenin, and attenuation of the fibrosis markers vimentin and fibronectin. No effective treatment is currently available in congenital muscular dystrophy and Glatiramer acetate may present a new potential treatment for this disorder. PMID- 20304649 TI - Preventing breast cancer in postmenopausal women by achievable diet modification: a missed opportunity in public health policy. AB - The Diet Modification trial of the Women's Health Initiative studies was reported to be inconclusive as the overall risk reduction was not statistically significant at the 0.05 level. By our calculation, the trial's demonstrated risk reduction at average adherence to a simple diet modification translates into avoiding 7.3% invasive breast cancers in post-menopausal women in the USA. The trial also demonstrated a clear dose response between diet modification and risk reduction, meaning a higher percentage of breast cancers can be avoided among women whose diet modification was better than average. Yet, the DM trial findings as reported and interpreted in public sent the message to post-menopausal women that reducing the fat intake does not reduce the risk of breast cancer. Clearly, a valuable opportunity to affect public health policy was missed because the contextual significance and policy implications of the findings were ignored. PMID- 20304650 TI - Differences in prognostic factors and patterns of failure between invasive micropapillary carcinoma and invasive ductal carcinoma of the breast: matched case-control study. AB - PURPOSE: We designed this study to identify differences in prognostic factors and patterns of failure between invasive micropapillary carcinoma (IMPC) and invasive ductal carcinoma (IDC) in patients with breast cancer. EXPERIMENTAL DESIGN: We identified 72 cases of IMPC who were diagnosed between 1999 and 2007 at the Samsung Medical Center. These patients were matched with 144 controls who were diagnosed with IDC during the same period. Exact matches were made for age (+/-3 years), pathologic tumour and node stage, and treatment methods (surgery and radiation therapy). RESULTS: The median follow-up period was 45 months (13-116) for IMPC and 50 months (16-122) for IDC. Lymphovascular invasion (LVI, p<0.0001), axillary lymph node extracapsular extension (ECE, p=0.001) and high nuclear grade (p=0.032) were more frequently detected in patients with IMPC. During the follow up period, treatment failed in 15 IMPC patients (20.8%) and in 26 IDC patients (18.1%). Loco-regional recurrences developed in 11 IMPC patients (15.3%) and eight IDC patients (5.6%). Importantly, of 57 IMPC patients who had positive axillary nodes, seven patients (12.3%) had axilla and/or supraclavicular recurrence. Therefore, at 5 years, the loco-regional recurrence-free survival was 79.1% in the IMPC patients vs. 93.3% in the IDC patients (p=0.0024). CONCLUSION: Our study showed that IMPC is associated with LVI, ECE, high nuclear grade, and a greater degree of loco-regional recurrence, especially in the axilla and supraclavicular areas. Therefore, axillary and supraclavicular radiation therapy should be considered in IMPC patients with axillary node metastasis. PMID- 20304651 TI - Sternal/para-sternal resection for parasternal local recurrence in breast cancer. AB - BACKGROUND: Locoregional recurrence occurs in a significant number of patients with breast cancer. This can result in substantial morbidity and mortality. Chest wall resection is well-documented for palliation and local control in chest wall relapse; an extension of this surgery is parasternal or sternal resection. METHODS: A retrospective review of medical records of eighteen women who underwent sternal or parasternal resection with curative intent between 1998 and 2007 was undertaken. RESULTS: 12 patients had total sternal resection, five patients had sub-total sternal resection and one patient had resection of tumour and ribs. 17 patients required the insertion of a composite Marlex((r)) methyl methacrylate chest wall prosthesis, followed by soft tissue reconstruction with a pectoralis major or latissimus dorsi flap, in the majority of cases. In-hospital and 30-day mortality was 0%. One and two-year overall survival was 87% and 80% respectively. The median recurrence-free survival was 18 months (95% CI 4-31 months). There was local and distant recurrence in one patient (5%), local recurrence in two patients (11%) and distant recurrence in eight patients (44%), with 15 out of 18 patients (77%) remaining free from local recurrence at 5 years. CONCLUSIONS: En bloc sternal resection for parasternal recurrence in breast cancer involves extensive surgery but in our experience can be performed with very low mortality and morbidity. In selected patients it provides good long term local control, relief of pain and improved cosmesis. PMID- 20304652 TI - Age-related changes in mechanical and metabolic energy during typical gait. AB - The purpose of the study was to investigate and report age-related changes in walking energy expenditure using different methods of energy estimation. For 81 children and 16 adults (3-35 years) energy expenditure was investigated by using the following methods: analysis of energy changes of the centre of body mass (external and internal mechanical work), sum of segmental energies, sum of net joint work and gross and net metabolic cost, as well as net non-dimensional oxygen cost. Different methods of energy estimation not only show different outcome results but also different age-related changes. Significant changes were found for negative net joint work, external mechanical work and recovery as well as sum of segmental energies, until 9, 11 and 19 years respectively. Positive net joint work showed no differences between age groups and the differences for internal work did not suggest development. Metabolic energy showed significant changes until adult age. Gross cost decreases with increasing age in children and, although more gradually, still in adolescents. Net and net non-dimensional cost shows a more constant decrease with increasing age until adulthood. Therefore, the choice of estimation method and the use of age-related reference data when evaluating young patients should be carefully considered. For interpretation of oxygen consumption in children the use of net is superior to gross cost, but even after net non-dimensional normalization, age-related reference data should be used. PMID- 20304653 TI - Reproducibility and validity of video screen measurements of gait in children with spastic cerebral palsy. AB - PURPOSE: To determine the reproducibility and validity of video screen measurement (VSM) of sagittal plane joint angles during gait. METHODS: 17 children with spastic cerebral palsy walked on a 10m walkway. Videos were recorded and 3d-instrumented gait analysis was performed. Two investigators measured six sagittal joint/segment angles (shank, ankle, knee, hip, pelvis, and trunk) using a custom-made software package. The intra- and interrater reproducibility were expressed by the intraclass correlation coefficient (ICC), standard error of measurements (SEM) and smallest detectable difference (SDD). The agreement between VSM and 3d joint angles was illustrated by Bland-Altman plots and limits of agreement (LoA). RESULTS: Regarding the intrarater reproducibility of VSM, the ICC ranged from 0.99 (shank) to 0.58 (trunk), the SEM from 0.81 degrees (shank) to 5.97 degrees (trunk) and the SDD from 1.80 degrees (shank) to 16.55 degrees (trunk). Regarding the interrater reproducibility, the ICC ranged from 0.99 (shank) to 0.48 (trunk), the SEM from 0.70 degrees (shank) to 6.78 degrees (trunk) and the SDD from 1.95 degrees (shank) to 18.8 degrees (trunk). The LoA between VSM and 3d data ranged from 0.4+/-13.4 degrees (knee extension stance) to 12.0+/-14.6 degrees (ankle dorsiflexion swing). CONCLUSION: When performed by the same observer, VSM mostly allows the detection of relevant changes after an intervention. However, VSM angles differ from 3d-IGA and do not reflect the real sagittal joint position, probably due to the additional movements in the other planes. PMID- 20304654 TI - Synthesis and pharmacological characterization of a new series of 5,7 disubstituted-[1,2,4]triazolo[1,5-a][1,3,5]triazine derivatives as adenosine receptor antagonists: A preliminary inspection of ligand-receptor recognition process. AB - A new series of triazolotriazines variously substituted at the C5 and N7 (5-25) positions was synthesized and fully characterized at the four adenosine receptor (AR) subtypes. In particular, arylacetyl or arylcarbamoyl moieties were introduced at the N7 position, which enhanced affinity at the hA(2B) and hA(3) ARs, respectively, when utilized on the pyrazolo-triazolopyrimidine nucleus as we reported in the past. In general, compounds with a free amino group at the 7 position (5, 6), showed good affinity at the rat (r) A(2A) AR (range 18.3 96.5nM), while the introduction of a phenylcarbamoyl moiety at the N7 position (12, 19, 24) slightly increased the affinity at the hA(3) AR (range 311-633nM) with respect to the unsubstituted derivatives. The binding profiles of the synthesized analogues seemed to correlate with the substitutions at the C5 and N7 positions. At the hA(2B) AR, derivative 5, which contained a free amino group at the 7 position, was the most potent (EC(50) 3.42microM) and could represent a starting point for searching new non-xanthine hA(2B) AR antagonists. Molecular models of the rA(2A) and hA(3) ARs were constructed by homology to the recently reported crystallographic structure of the hA(2A) AR. A preliminary receptor driven structure-activity relationship (SAR) based on the analysis of antagonist docking has been provided. PMID- 20304655 TI - Antiproliferative activity of synthetic naphthoquinones related to lapachol. First synthesis of 5-hydroxylapachol. AB - A series of 5-hydroxy-1,4-naphthoquinones analogues was synthesized from juglone (6) and their antiproliferative activity against a representative panel of six human solid tumor cell lines has been investigated. The 2,5-dihydroxy-3-(3 methylbut-2-enyl)naphthalene-1,4-dione (4) and 2,3-dihydro-5-hydroxy-2-(prop-1-en 2-yl)naphtho[2,3-b]furan-4,9-dione (27) were the most potent antiproliferative agents with GI(50) values of 0.42-8.1 and 0.80-2.2microM, respectively. The results provide insight into the correlation between some structural properties of 5-hydroxynaphthoquinones and their antiproliferative activity. PMID- 20304656 TI - Chromene-3-carboxamide derivatives discovered from virtual screening as potent inhibitors of the tumour maker, AKR1B10. AB - A human aldose reductase-like protein, AKR1B10 in the aldo-keto reductase (AKR) superfamily, was recently identified as a therapeutic target in the treatment of several types of cancer. In order to identify potential leads for new inhibitors of AKR1B10, we adopted the virtual screening approach using the automated program icm, which resulted in the discovery of several chromene-3-carboxamide derivatives as potent competitive inhibitors. The most potent (Z)-2-(4 methoxyphenylimino)-7-hydroxy-N-(pyridin-2-yl)-2H-chromene-3-carboxamide inhibited the reductase activity of AKR1B10 with a K(i) value of 2.7nM, and the metabolism of farnesal and 4-hydroxynonenal in the AKR1B10-overexpressed cells from 0.1microM with an IC(50) value equal to 0.8microM. PMID- 20304657 TI - Synthesis, molecular modeling and biological evaluation of PSB as targeted antibiotics. AB - We described here the design, synthesis, molecular modeling, and biological evaluation of a series of peptide and Schiff bases (PSB) small molecules, inhibitors of Escherichia coli beta-Ketoacyl-acyl carrier protein synthase III (ecKAS III). The initial lead compound was reported by us previously, we continued to carry out structure-activity relationship studies and optimize the lead structure to potent inhibitors in this research. The results demonstrated that both N-(2-(3,5-dichloro-2-hydroxybenzylideneamino)propyl)-2-hydroxybenzamide (1f) and 2-hydroxy-N-(2-(2-hydroxy-5-iodobenzylideneamino)propyl)-4 methylbenzamide (3e) posses good ecKAS III inhibitory activity and well binding affinities by bonding Gly152/Gly209 of ecKAS III and fit into the mouth of the substrate tunnel, and can be as potential antibiotics agent, displaying minimal inhibitory concentration values in the range 0.20-3.13microg/mL and 0.39 3.13microg/mL against various bacteria. PMID- 20304658 TI - Total synthesis, antiprotozoal and cytotoxicity activities of rhuschalcone VI and analogs. AB - The total synthesis of a potent antiplasmodial natural bichalcone, rhuschalcone VI, is described starting from simple and available resorcinol and 4 hydroxybenzaldehyde. Key steps include the solvent-free Aldol syntheses of chalcones, and the successful application of the Suzuki-Miyaura coupling reaction in the synthesis of bichalcones. The present work constitutes a general method for the rapid syntheses of a number of bichalcones related to rhuschalcone VI. Some of the bichalcones showed moderate antiprotozoal activities against Bodo caudatus, a preliminary screening system for antitrypanosomal activities, most of them with little or no cytotoxicity. PMID- 20304659 TI - Conjugates of plumbagin and phenyl-2-amino-1-thioglucoside inhibit MshB, a deacetylase involved in the biosynthesis of mycothiol. AB - N-Acetylglucosaminylinositol (GlcNAc-Ins)-deacetylase (MshB) and mycothiol-S conjugate amidase (Mca), structurally related amidases present in mycobacteria and other Actinomycetes, are involved in the biosynthesis of mycothiol and in the detoxification of xenobiotics as their mycothiol-S-conjugates, respectively. With substrate analogs of GlcNAc-Ins, MshB showed a marked preference for inositol as the aglycon present in GlcNAc-Ins. The inhibition of MshB and Mca by 10 thioglycosides, 7 cyclohexyl-2-deoxy-2-C-alkylglucosides, and 4 redox cyclers was evaluated. The latter contained plumbagin tethered via 2 to 5 methylene carbons and an amide linkage to phenyl-2-deoxy-2-amino-1-thio-alpha-d-glucopyranoside. These proved to be the most potent amongst the 21 compounds tested as inhibitors of MshB. Their inhibitory potency varied with the length of the spacer, with the compound with longest spacer being the most effective. PMID- 20304660 TI - Some geological characteristics in a regolith-limey shale rock profile through natural radionuclides distribution. AB - The objective of this work is to study some geological characteristics in a regolith-rock profile by analyzing the distribution of natural radionuclides along the profile by high resolution gamma ray spectrometry. The concentrations of radionuclides reflect some mineralogical characteristics of the rock matrix and also more recent events, such as weathering and erosion. The samples were collected in an abandoned limestone mine, in the city of Sapopema, Parana State, Brazil. The stratigraphy is represented by an alternation of decimetric limestone layers, bituminous shale and some rhythmite layers. The ratios eTh/K obtained for all samples of the studied profile have equivalent values, indicating similar mineralogical characteristics of their detritic components. The ratio eTh/eU corroborates the fact that regolith samples belong to a much more oxidized environment, favoring the leaching of uranium. These results show that the measurement of radionuclide distribution in rocks and soils may be an important tool for the analysis of geological characteristics, such as mineralogy and oxidizing conditions. PMID- 20304661 TI - Ethical issues in instructions to authors of journals in oral craniomaxillofacial/facial plastic surgery and related specialties. AB - BACKGROUND: Ethical standards of biomedical publications are associated with editorial leadership, such as contents of instructions to authors and journal's mechanisms for research and publication ethics. OBJECTIVES: To compare ethical issues in the guidelines for authors in oral-craniomaxillofacial/facial plastic surgery (OCM-FPS) journals with those in plastic surgery and otorhinolaryngology/head and neck surgery (ORL-HNS) journals, and to evaluate the relationship between journal's impact factor (IF) and ethical issues in the instructions to authors. METHODS: This study used a cross-sectional study design. The predictor variables were journal's specialty and IF. The outcome variable was the presence of seven ethical issues in the online versions of journal's instructions to authors in October 2009. We included only journals with identifiable IF for 2008, published in English, French, German and Thai. Appropriate descriptive and univariate statistics were computed for all study variables. The level of statistical significance was set at P<0.05. RESULTS: The sample was composed of 48 journals: seven OCM-FPS (14.6%), 14 plastic surgery (29.2%) and 27 ORL-HNS (56.2%) journals. Only four journals (8.3%) mentioned all ethical issues in their guidelines for authors. Neither journal's specialty nor IF was linked to completeness of the ethical requirements. CONCLUSIONS: The results of this study suggest that ethical issues in the instructions to authors of most IF-indexed journals in OCM-FPS, plastic surgery and ORL-HNS are incomplete, regardless of specialty and IF. There is room for substantial improvement to uphold scientific integrity of these surgical specialties. PMID- 20304662 TI - Integrated cerebral perfusion for hypothermic circulatory arrest during transverse aortic arch repairs. AB - OBJECTIVES: Antegrade cerebral perfusion (ACP) during hypothermic circulatory arrest (HCA) for ascending/transverse arch repair is used for cerebral protection. This study evaluates ACP in combination with retrograde cerebral perfusion (RCP) during extended HCA and compares it to RCP-only. METHODS: Between January 2005 and April 2007, we performed 64 consecutive arch repairs requiring extended HCA (>40 min). RCP-only was used with 34 patients and ACP with brief RCP ('integrated') was used with 30 patients. Mean HCA time was 51 + or - 13 min. Mean RCP-only time was 47 + or - 9.6 min; in the integrated group, mean ACP time was 42 + or - 14.4 min with an added RCP time of 10.8 + or - 7.6 min. For the entire cohort, 95% (61/64) underwent total arch repair, and 67% (43/64) had elephant trunk reconstruction. Variables predictive of mortality and neurological outcomes were analysed prospectively, but technique selection was non-randomised. RESULTS: Preoperative and operative variables did not differ between the RCP-only and the integrated groups except for aortic valve replacement, which was more frequently performed in the integrated group (33% (10/30) vs 12% (4/34), P=0.05), and preoperative renal dysfunction, which was more frequent in the RCP group (26% (9/34) vs 7% (2/30), P=0.04). No significant difference was observed in outcomes between the groups; however, the integrated group had higher mortality, stroke and temporary neurological deficit than RCP-only. CONCLUSIONS: The observed trends in actual outcomes were a cause for concern. ACP combined with a short period of RCP did not provide better outcomes than RCP-only. The use of RCP remains warranted in our experience. PMID- 20304663 TI - Is endovascular repair the new gold standard for primary adult coarctation? AB - OBJECTIVE: Primary adult aortic coarctation (PAAC) is an unusual cause of hypertension. The standard of care includes surgical repair, which can be associated with considerable morbidity and operative risk. Although balloon angioplasty has been successfully used in paediatric and adolescent patients with coarctation, little information exists regarding the endovascular repair of PAAC. This study examines the procedural safety and efficacy of endovascular repair of PAAC along with midterm outcomes. METHODS: Between January 2000 and July 2008, 16 patients underwent endovascular repair of PAAC. All patients were hypertensive with 13 patients (81.3%) receiving medical therapy. Symptoms included chest pain (n=11, 69%), progressive fatigue (n=5, 31%), exercise intolerance (n=4, 25%) and shortness of breath (n=3, 19%). Associated cardiac concerns included depressed ejection fraction (n=6, 38%), pulmonary hypertension (n=5, 31%), ascending aortic dilatation (n=5, 31%) and bicuspid aortic valve (n=4, 25%). Endovascular repair was achieved using a percutaneous femoral approach. Balloon angioplasty of the coarctation was performed prior to treatment using a balloon-expandable uncovered stent. Aortic diameters were assessed using intravascular ultrasound. Pre- and post-procedure pressure gradients were measured and success was determined as a residual pressure gradient across the treated aorta of less than 20 mmHg. RESULTS: The male:female (M:F) ratio was 9:7 with a mean age of 39.7 years. Procedural success was 100%. Mean pre-procedural aortic diameter was 8.4mm (3-14 mm) and mean post-procedural aortic diameter was 16.3mm (10-20mm) (p=0.04). The mean pre-procedural pressure gradient was 48.3 mmHg (25-100 mmHg) and the mean post-procedural pressure gradient was 0.5 mmHg (0-15 mmHg) (p=0.05). Twelve patients received one stent, two patients received two stents, one patient received three stents and one other patient received a thoracic stent graft. The rate of paraplegia was 0% with no blood transfusions, strokes or deaths. Follow up ranged from 12 to 72 months (mean=22.8 months). One patient required re intervention with an additional stent 14 months following the initial procedure and all the patients remain symptom-free. CONCLUSION: Endovascular repair of PAAC is safe and effective and compares favourably with open surgical repair. Midterm follow-up suggests that the treatment is durable and may be an alternative to surgical repair. Although this is the largest endovascular treatment series for PAAC reported to date, additional study and follow-up are needed. PMID- 20304664 TI - The influence of the 'golden 24-h rule' on the prognosis of oesophageal perforation in the modern era. AB - OBJECTIVES: Rupture of the oesophagus is a surgical emergency with significant morbidity and mortality. We present our experience in managing such patients in a tertiary care cardiothoracic unit. METHODS: We conducted a retrospective clinical review of patients who were admitted following rupture of the oesophagus over a period of 6 years (2002-2008). RESULTS: In our unit, there were 27 admissions following isolated rupture of the oesophagus, of which 18 were males and nine were females. The median age was 65 years (range 22-87). Twenty-four (89%) presented with spontaneous perforations (Boerhaave's syndrome) and three (11%) were iatrogenic. Primary surgical repair was done in 21 (77%) patients, a two stage repair in 8% and conservative management in 16.6%. Mean hospital stay was 31 days (range 13-80 days). Overall, in-hospital mortality was five out of 27 patients (18.5%). Time from onset of symptoms to diagnosis of oesophageal perforation was early (<24 h) in 17 (63%) patients and late (>24 h) in the remaining 10 (37%) patients. In four out of the five non-survivors, there was a >24-h delay in diagnosis. The mortality rate among patients with a delayed diagnosis was 40% compared to 6.2% among those who were diagnosed in <24 h (p=0.047). CONCLUSIONS: Our review confirms that an early diagnosis and management ('golden 24 h') are crucial for successful outcome in patients with rupture of the oesophagus. We reiterate the importance of critical care support, particularly in the early stages of management. For early detection, the primary and secondary care sectors need to be better educated. PMID- 20304665 TI - Preoperative introduction and maintenance immunosuppression therapy of oral-only tacrolimus, mycophenolate mofetil and steroids reduce acute rejection episodes after lung transplantation. AB - OBJECTIVE: Immunosuppression therapy in lung transplantation (LTX) remains unsatisfactory due to a high incidence of infection and frequent acute rejection (AR), leading to early onset of the bronchiolitis obliterans syndrome (BOS). The long-term success of LTX is limited by BOS, associated with marked morbidity and mortality. The strongest risk factor for BOS is frequent AR. Decreasing frequent AR episodes might lead to improved long-term survival following LTX. METHODS: Despite the introduction of many novel agents, the basis of currently applied protocols remains a calcineurin inhibitor, that is, cyclosporine/tacrolimus (TAC). Eighty-two lung recipients received oral-only administered immunosuppression with oral TAC, mycophenolate mofetil (MMF) and intravenous (IV) methylprednisolone as introduction 2h prior to skin incision. Intra-operatively, patients received additional methylprednisolone prior to unclamping the pulmonary arteries. Postoperatively oral TAC/MMF and prednisolone were continued and trough levels closely monitored (target 8-12 ng ml(-1)). Pulmonary function tests were performed frequently and daily after discharge by means of a self-measuring device (daily forced expiratory volume in 1s (FEV(1))) as the major part of a close follow-up and monitoring programme. Trans-bronchial biopsies were rarely performed. Patient data were collected prospectively and stored in transplantation registries. LTX survival was analysed according to the Kaplan Meier method. RESULTS: The follow-up of the LTX patients through frequent ambulatory care unit visits and close monitoring of the immunosuppressive regimen and the medication response was 100% complete. The mean duration of observation per patient was 1.8 + or - 1.7 years (median 1.4, range: 0.0-6.4 years) and this study included 176.5 patient-related years of follow-up. The 1-, 3- and 5-year survival following LTX was 70%, 60% and 55%, respectively. Eight patients (10%) underwent high-dose intravenous (IV) bolus methylprednisolone treatment and taper for AR. Two additional patients developed BOS more than 4 years following LTX. The AR- and BOS-related mortality was 0% within the 7-year interval of LTX. Alterations in FEV(1) were associated with significant anastomotic airway and infectious complications, requiring frequent bronchoscopic interventions, stenting and laser therapy as well as frequent IV antibiotic treatment. The 30 day and in-hospital mortality of 19.5% was markedly related to primary graft failure and viral infection. Long-term survival was limited predominantly by cytomegalovirus (CMV) infection and sepsis. CONCLUSIONS: Our results suggest that a standard immunosuppressive regimen of TAC and MMF orally administered and introduced prior to skin incision for LTX surgery and maintained long-term might reduce the incidence of acute and chronic rejection. Viral infections and not BOS seemed to be the limiting factor of long-term survival. PMID- 20304666 TI - Primary isolated aortic valve surgery in octogenarians. AB - OBJECTIVES: We reviewed our surgery registry, to identify predictive risk factors for operative results, and to analyse the long-term survival outcome in octogenarians operated for primary isolated aortic valve replacement (AVR). METHODS: A total of 124 consecutive octogenarians underwent open AVR from January 1990 to December 2005. Combined procedures and redo surgery were excluded. Selected variables were studied as risk factors for hospital mortality and early neurological events. A follow-up (FU; mean FU time: 77 months) was obtained (90% complete), and Kaplan-Meier plots were used to determine survival rates. RESULTS: The mean age was 82+/-2.2 (range: 80-90 years; 63% females). Of the group, four patients (3%) required urgent procedures, 10 (8%) had a previous myocardial infarction, six (5%) had a previous coronary angioplasty and stenting, 13 patients (10%) suffered from angina and 59 (48%) were in the New York Heart Association (NYHA) class III-IV. We identified 114 (92%) degenerative stenosis, six (5%) post-rheumatic stenosis and four (3%) active endocarditis. The predicted mortality calculated by logistic European System for Cardiac Operative Risk Evaluation (EuroSCORE) was 12.6+/-5.7%, and the observed hospital mortality was 5.6%. Causes of death included severe cardiac failure (four patients), multi organ failure (two) and sepsis (one). Complications were transitory neurological events in three patients (2%), short-term haemodialysis in three (2%), atrial fibrillation in 60 (48%) and six patients were re-operated for bleeding. Atrio ventricular block, myocardial infarction or permanent stroke was not detected. The age at surgery and the postoperative renal failure were predictors for hospital mortality (p value <0.05), whereas we did not find predictors for neurological events. The mean FU time was 77 months (6.5 years) and the mean age of surviving patients was 87+/-4 years (81-95 years). The actuarial survival estimates at 5 and 10 years were 88% and 50%, respectively. CONCLUSIONS: Our experience shows good short-term results after primary isolated standard AVR in patients more than 80 years of age. The FU suggests that aortic valve surgery in octogenarians guarantees satisfactory long-term survival rates and a good quality of life, free from cardiac re-operations. In the era of catheter-based aortic valve implantation, open-heart surgery for AVR remains the standard of care for healthy octogenarians. PMID- 20304667 TI - Impact of preoperative atrial fibrillation on the late outcome of off-pump coronary artery bypass surgery. AB - OBJECTIVE: The impact of pre-existing atrial fibrillation on the long-term outcome in patients after off-pump coronary revascularisation is not well known. This study aims to determine the independent effects of preoperative atrial fibrillation on the early and late outcomes of off-pump coronary artery bypass surgery. METHODS: A total of 513 patients undergoing isolated coronary artery bypass surgery using off-pump approach between 2000 and 2005 were studied. Twenty six of them (5.1%) had preoperative atrial fibrillation (15 had paroxysmal atrial fibrillation and 11 had persistent or permanent atrial fibrillation) and the other 487 patients were in normal sinus rhythm. Early and late outcomes were compared retrospectively between patients with preoperative atrial fibrillation and patients in sinus rhythm. The median follow-up period for the entire study population was 3.3 + or - 2.7 years. RESULTS: The baseline characteristics of the patients with preoperative atrial fibrillation were generally similar to those of patients in sinus rhythm. However, the patients with atrial fibrillation had a significantly lower left ventricular ejection fraction compared with those in sinus rhythm (50 + or - 15 vs 56 + or - 12%, p=0.03). The mean age of the atrial fibrillation group was almost 3 years more than that of the sinus rhythm group. Operative mortality was similar in patients with atrial fibrillation (3.8%) and those in sinus rhythm (1.0%). Ten patients developed cerebral infarction within 7 days after surgery, including one patient (3.8%) from the atrial fibrillation group and nine patients (1.8%) from the sinus rhythm group. Long-term survival was significantly decreased in the atrial fibrillation group (5-year survival: 70 + or - 9.6% vs 87 + or - 1.8%; p=0.0018). Freedom from cerebral complications was also significantly decreased in the atrial fibrillation group (5-year survival: 85 + or - 8.3% vs 95 + or - 1.2%; p=0.0009), but there were no differences in cardiac death and major cardiac adverse events. On Cox proportional hazards regression analysis, preoperative atrial fibrillation was a significant adverse predictor for survival (hazard ratio=3.0, 95% confidence intervals (CIs) 1.3-6.9; p=0.009) and independent predictor of late cerebral infarction (hazard ratio=6.2, 95% CIs 2.0-19.3; p=0.0002). CONCLUSIONS: Uncorrected preoperative atrial fibrillation is strongly associated with poor long-term survival and increased late cerebral complications after off-pump coronary artery bypass surgery. Concomitant atrial fibrillation surgery should be considered to improve the long term results of surgical revascularisation. PMID- 20304668 TI - A patch plasty to inferior pulmonary vein: when more release is needed. PMID- 20304669 TI - Targeting immune suppressing myeloid-derived suppressor cells in oncology. AB - Emerging data suggests that host immune cells with a suppressive phenotype represent a significant hurdle to successful therapy for metastatic cancer. Among the suppressor cells, T regulatory cells (Treg) and myeloid-derived suppressor cells (MDSC) are significantly increased in hosts with advanced malignancies. MDSC mediate the suppression of the tumor antigen-specific T cell response through the induction of T cell anergy and the development of Treg in tumor bearing mice. These results provide robust evidence of an in vivo immunoregulatory function of MDSC in the establishment of tumor antigen-specific tolerance and the development of Treg in tumor-bearing hosts. To achieve effective anti-tumor immunity, tumor-induced immunosuppression must be reversed. Our preliminary results indicate that c-kit ligand (stem cell factor) expressed by tumor cells may be required for MDSC accumulation in tumor-bearing mice, and that blocking the c-kit ligand/c-kit receptor interaction can prevent the development of Treg and reverse immune tolerance induced by MDSC. Since c-kit can be readily inhibited by several small molecule inhibitors including imatinib, sunitinib and dasatinib, targeting immune suppressing cells can be readily accomplished in the clinic. PMID- 20304670 TI - Immune surveillance of the maternal/fetal interface: controversies and implications. AB - How the fetal 'allograft' avoids rejection during pregnancy remains a major unresolved immunological paradox. Recent work has suggested that fetomaternal tolerance is in fact maintained by a number of redundant mechanisms, but their relative importance has remained poorly defined. In this paper, I discuss an emerging controversy regarding the ability of maternal T cells to mediate fetal rejection at a time when they appear to be ignorant of fetal and placental antigens. This paradox within a paradox highlights two major research directions in the field of reproductive immunology that, when ultimately reconciled, promise to give significant insight into mechanisms of impaired fertility and compromised fetal and maternal health. PMID- 20304671 TI - Is prolactin the cardinal calciotropic maternal hormone? AB - To produce offspring, mothers require a large amount of calcium for fetal growth and milk production. Increased calcium demand leads to enhanced intestinal calcium absorption and stockpiling of bone calcium in pregnancy prior to demineralization in lactation. These coordinated events must be carefully organized by calciotropic hormone(s), but the classical hormones, namely 1,25 dihydroxyvitamin D(3), parathyroid hormone and calcitonin, do not appear to be responsible. Plasma prolactin (PRL) levels are elevated during pregnancy and, in view of the presence of PRL receptors in gut, bone and mammary glands, as well as recent evidence of the stimulatory effects of PRL on intestinal calcium transport, bone resorption and mammary calcium secretion, we postulate that PRL is the cardinal calciotropic hormone during pregnancy and lactation. PMID- 20304672 TI - Separation of isomers L-alanine and sarcosine in urine by electrospray ionization and tandem differential mobility analysis-mass spectrometry. AB - Sarcosine, an isomer of L-alanine, has been proposed as a prostate cancer progression biomarker [1]. Both compounds are detected in urine, where the measured sarcosine/alanine ratio has been found to be higher in prostate biopsy positive group versus controls. We present here preliminary evidence showing that urine samples spiked with sarcosine/alanine can be partially resolved in 3 min via tandem differential mobility analysis-mass spectrometry (DMA-MS). Based on the calibration curves obtained for two mobility peaks, we finally estimate their concentration ratio in urine. PMID- 20304673 TI - Scanwave: a new approach to enhancing spectral data on a tandem quadrupole mass spectrometer. AB - A new type of mass analyzer is described, which allows low-resolution axial ion ejection to be obtained from a traveling wave based, stacked ring collision cell. Linking this ejection temporally with the scanning of the second quadrupole of a tandem quadrupole mass spectrometer provides an improvement in sampling duty cycle, which results in significant signal intensity improvements for scanning acquisitions such as product ion spectra. A near 100% storage efficiency is enabled by a split cell design, which allows ion fragmentation and accumulation to be performed in one section of the collision cell whilst previously accumulated ions are simultaneously ejected from the rear of the cell. These characteristics combine to give an m/z-dependent signal gain of 7-20x over a conventional scanning quadrupole for a 1000 Th scan. The ability to swap very rapidly from a non-enhanced mode of operation to an enhanced mode whilst retaining the existing sensitivity, speed, and functionality of a conventional tandem quadrupole mass spectrometer is also described. PMID- 20304674 TI - Electron transfer dissociation with supplemental activation to differentiate aspartic and isoaspartic residues in doubly charged peptide cations. AB - Electron-transfer dissociation (ETD) with supplemental activation of the doubly charged deamidated tryptic digested peptide ions allows differentiation of isoaspartic acid and aspartic acid residues using the c + 57 or z*-57 peaks. The diagnostic peak clearly localizes and characterizes the isoaspartic acid residue. Supplemental activation in ETD of the doubly charged peptide ions involves resonant excitation of the charge reduced precursor radical cations and leads to further dissociation, including extra backbone cleavages and secondary fragmentation. Supplemental activation is essential to obtain a high quality ETD spectrum (especially for doubly charged peptide ions) with sequence information. Unfortunately, the low-resolution of the ion trap mass spectrometer makes detection of the diagnostic peak, [M-60], for the aspartic acid residue difficult due to interference with side-chain loss from arginine and glutamic acid residues. PMID- 20304675 TI - Arterial embolization for the management of gastrointestinal hemorrhage from metastatic renal cell carcinoma. AB - Patients with renal cell carcinoma (RCC) involving the gastrointestinal (GI) tract may present with hemorrhage. Eight arterial embolization procedures were performed to treat five upper GI lesions and one ileal metastatic RCC lesion in five patients with GI bleeding. Control of GI hemorrhage for at least 30 days was achieved following six of the eight embolizations (75%) in four of the five patients (80%). Duration of response ranged from 1 to 26 months. Complications including GI ischemia and nontarget embolization were not encountered. Arterial embolization can be used safely for palliation of hemorrhage from RCC metastases to the GI tract. PMID- 20304676 TI - Quality improvement guidelines for percutaneous needle biopsy. PMID- 20304677 TI - Three-year outcomes after kyphoplasty in patients with osteoporosis with painful vertebral fractures. AB - PURPOSE: Kyphoplasty immediately improves pain and mobility in patients with painful osteoporotic vertebral fractures, but long-term clinical outcomes are still unclear. This controlled trial evaluates pain, mobility and fracture incidence 3 years after kyphoplasty. MATERIALS AND METHODS: Kyphoplasty was performed in 40 patients with painful osteoporotic vertebral fractures; 20 patients who were selected for kyphoplasty but chose not to undergo the procedure served as controls. All patients received pharmacologic antiosteoporosis treatment, pain medication, and physiotherapy. Pain (visual analog scale of 0 100), mobility (European Vertebral Osteoporosis Study questionnaire score of 0 100), and incident vertebral fractures were assessed at baseline, postprocedurally, and after 12 and 36 months. RESULTS: Pain score improved after kyphoplasty from 73.8 to 55.9 (immediately after kyphoplasty), 55.6 (12 months), and 54.0 (36 months; P < .001). Pain score in the control group changed from 66.4 to 65.7 at 12 months and 64.0 at 36 months (P = .521). The pain score of the kyphoplasty group was significantly improved versus controls after 36 months (P = .023). Mobility score improved after kyphoplasty from 43.8 to 54.2 (immediately after kyphoplasty), 54.5 (12 months), and 54.8 (36 months; P = .0008) and remained increased (P = .308) compared with controls (39.8 immediately after kyphoplasty, 44.3 at 12 months, and 43.6 at 36 months). The incidence of new vertebral fractures after kyphoplasty was significantly reduced versus controls after 3 years (P = .0341). CONCLUSIONS: Kyphoplasty reduces pain and improves mobility as long as 3 years after the procedure. The long-term risk of new vertebral fractures after kyphoplasty of chronically painful vertebral fractures is reduced versus controls. PMID- 20304678 TI - Treatment of recurrent carotid cavernous fistula by direct puncture of a previously trapped internal carotid artery. AB - Treatment of direct carotid cavernous fistulas has evolved from surgical ligation and trapping to endovascular techniques. Endovascular therapy allows occlusion of the fistula while preserving the parent carotid artery. The present report describes a case of direct carotid cavernous fistula that was initially treated with the trapping procedure 21 years earlier. The patient had a recurrent direct carotid cavernous fistula and was treated successfully with embolization by means of direct percutaneous puncture of the carotid artery above the trapped level. Direct puncture of the carotid artery is an alternative treatment in patients who lack safe access for direct carotid cavernous fistula embolization. PMID- 20304679 TI - Hybrid thoracoabdominal aortic aneurysm repair: visceral revascularization combined with endovascular abdominal and thoracic aneurysm repair. AB - Hybrid approaches for the treatment of thoracoabdominal aortic aneurysms (TAAAs) by using a combination of visceral revascularization followed by thoracic endovascular aneurysm repair (EVAR) have been reported with acceptable results. The authors present a case that required the addition of a bifurcated infrarenal EVAR to completely exclude a type III TAAA. PMID- 20304680 TI - Safety and efficacy of renal artery stenting following suboptimal renal angioplasty for de novo and restenotic ostial lesions: results from a nonrandomized, prospective multicenter registry. AB - PURPOSE: This registry was designed to evaluate the Bridge Extra Support renal stent system (Medtronic, Santa Rosa, California) in the treatment of renal artery ostial lesions following suboptimal percutaneous transluminal renal angioplasty (PTRA). MATERIALS AND METHODS: This consecutive, nonrandomized, prospective, multicenter registry enrolled 188 patients between April 1999 and May 2002 with single de novo or restenotic renal artery ostial lesions (>or=70% stenosis) who underwent implantation of a balloon-expandable stent immediately following unsuccessful PTRA. Primary safety endpoints were major adverse clinical events (MACE) at 30 days and 9-12 months. The primary efficacy endpoint was absence of binary restenosis at 9-12 months with duplex ultrasonography (US). Secondary endpoints were acute success and quality-of-life (QOL) improvements (blood pressure, antihypertensive medications, renal function). The long-term effect of renal artery stenting on blood pressure and renal function was assessed to 36 months. RESULTS: The acute procedure and clinical success rates were 92.9%. At 30 days, the MACE rate was 3.2%, with no instances of target lesion revascularization (TLR). At 9-12 months, the MACE rate was 16.5%, with five (2.7%) deaths and 14 (7.4%) instances of TLR. The rate of restenosis at 9-12 months with duplex US was 12.6%, and 94% of patients had QOL improvements. A significant reduction in systolic blood pressure occurred following renal artery stenting and persisted to 36 months. CONCLUSIONS: Renal artery stenting is safe and efficacious in the treatment of single de novo and restenotic renal artery ostial lesions following suboptimal PTRA. PMID- 20304681 TI - Benefit of early conversion from CNI-based to everolimus-based immunosuppression in heart transplantation. AB - BACKGROUND: Calcineurin inhibitor (CNI)-induced nephrotoxicity is a feared adverse effect after heart transplantation (HTx). In patients with advanced renal failure we performed an overnight conversion from cyclosporine (CsA) to everolimus within the first year after HTx and compared changes in renal function to a similar switch performed in a group of long-term HTx survivors with 24-month follow up. METHODS: Sixteen HTx recipients (Group 1), including 5 patients undergoing dialysis, were switched overnight from CsA to everolimus at 5.5 (range 1.3 to 8.5) months post-operatively, whereas 15 patients completed 24 months of follow-up. Fifteen long-term survivors (Group 2) were recruited at 96 (58 to 148) months post-HTx. Due to 3 withdrawals and 2 deaths, 10 of these 15 patients remained available for follow-up assessment. RESULTS: In Group 1 patients, creatinine level improved from 211 (186 to 263) to 112 (98 to 140) mumol/liter and estimated glomerular filtration rate (eGFR) from 29 (20 to 35) to 62 (43 to 69) ml/min/1.73 m(2) (p < 0.001). In Group 2, creatinine decreased from 227 (188 to 255) to 193 (150 to 250) micromol/liter (p = 0.299), and eGFR increased from 26 (21 to 31) to 28 (22 to 35) ml/min/1.73 m(2) (p = 0.225). Four cellular rejections were treated successfully in Group 1. All together, 24 adverse events occurred. CONCLUSIONS: These preliminary data are the first to suggest that the improvement in renal function after switching to CNI-free everolimus treatment has the greatest potential within the first year post-HTx. While we await randomized, controlled trials, it appears that conversion can be performed with acceptable safety in selected patients. PMID- 20304682 TI - Post-transplant lymphoproliferative disorder in pediatric heart transplant recipients. AB - BACKGROUND: Post-transplantation lymphoproliferative disorder (PTLD) is a major cause of morbidity and mortality after pediatric heart transplantation. METHODS: Heart transplant recipients at The Hospital for Sick Children, Toronto, from 1990 to May 2008, were reviewed. Competing risk hazard analysis was used to model the natural history of the disease. Patients were matched for gender and duration of follow-up to identify potential covariates associated with increased risk of PTLD. RESULTS: A total of 173 heart transplant recipients (42% <1 year old) were reviewed. Twenty-three developed PTLD at a median of 4 years post transplantation. After transplantation, PTLD affected 9%, 15% and 28% at 3, 5 and 10 years, respectively. Freedom from death or PTLD recurrence was 72%, 58% and 50% at 1, 3 and 5 years, respectively, after PTLD diagnosis. Higher maximum Epstein-Barr viral (EBV) load (hazard ratio [HR]: 2.6, p = 0.004) and longer duration of induction therapy (HR: 1.7, p = 0.02) were associated with increased risks of PTLD. Higher cumulative cyclosporine doses over the first year post transplantation were associated with increased risks of PTLD (HR: 1.2 per 1 mg/kg/day equivalent, p = 0.03), but higher tacrolimus doses were not (p = 0.38). Patients on cyclosporine at 6 months post-transplantation were at higher risk of PTLD than those on tacrolimus (HR: 5.2, p = 0.003). The use of anti-viral prophylaxis in patients with high EBV load may provide some protection (HR: 7.6 vs 15.4 with no anti-viral, p = 0.02). CONCLUSIONS: PTLD is a major concern in pediatric heart transplant recipients and is associated with high morbidity/mortality. Exposure to EBV and higher intensity of immunosuppression seems to be associated with increased risk. PMID- 20304683 TI - Duplex-guided endovascular repair of popliteal artery aneurysms (PAAs): a new approach to avert the use of contrast material and radiation exposure. AB - OBJECTIVE: Our previously reported experience with balloon angioplasties and stenting for occlusive infra-inguinal arterial disease using duplex guidance encouraged us to expand the indication for this imaging modality to include endovascular repair of popliteal artery aneurysms (PAAs). The present study evaluated the feasibility of performing this procedure under duplex guidance alone. METHODS: Fifteen patients (14 males and one female) underwent duplex guided placement of Viabahn stented grafts (7-10mm) for repair of PAAs over the last 50 months. The mean of patients' age was 80+/-6 years (range: 66-92 years). Fifty-three percent of these patients had chronic renal failure. The mean PAA diameter was 22+/-12 mm (range: 12-57 mm). Only two patients (13%) had no direct run-off to the foot. Pre-procedure mean PA volume flow (mPAVF) was 73+/-39 ml/min. None of the patients received contrast material or radiation exposure. RESULTS: Fourteen endografts were placed percutaneously under local anaesthesia, and the remaining graft was placed during an open repair of an ipsilateral common femoral artery aneurysm under regional nerve block. Both the proximal and distal ends of the endograft were placed at least 2.5 cm into a non-dilated segment of the recipient artery. The post-procedure mPAVF was 137+/-38 ml/min (range: 80-210 ml/min). There were no local complications. Three patients developed graft thrombosis at 2, 5 and 30 months post-procedure. The first two patients had no direct flow into the foot and had post-procedure mPAVF <100ml/min. The remaining 12 endografts are patent from 1 month to 32 months (mean: 12+/-13 months). These patients had post-procedure mPAFV >100ml/min. Two patients (13%) died at 1 month (respiratory failure) and 3 months (intracranial haemorrhage) post-procedure. CONCLUSIONS: Endovascular repair of PAAs with Viabahn stented grafts can be performed under duplex guidance alone. This imaging modality appears to be safe and reliable and it may be particularly beneficial in patients with renal failure. Poor run-off and low mPAVF (<100 ml/min) may be predictors of poor graft patency. To our knowledge, this is the first report of duplex-guided endovascular repair of PAAs. PMID- 20304684 TI - Ready-to-fenestrate stent grafts in the treatment of juxtarenal aortic aneurysms: proposal for an off-the-shelf device. AB - OBJECTIVE: A prototype ready-to-fenestrate stent graft (RFSG) was designed with a fixed scallop, and eight potential fenestrations allowing for variation in the position of each renal artery (RA) relative to the superior mesenteric artery (SMA). We aimed to determine the proportion of juxtarenal aneurysms treatable using this potentially 'off-the-shelf' device. METHODS: A total of 439 consecutive orders for custom-made devices were analysed, and positions for potential fenestrations in the RFSG were determined, based on the most frequent anatomical target vessel variations: a fixed SMA scallop 12 mm deep at 12:00, RA fenestrations at 9:15, 10:15 (target within the range 8:45-10:45), 2:15 and 3:15 (target within the range 1:45-3:45), each either 19 or 28 mm from the graft edge (GE); (within the range 15-32 mm), and 6 x 8 mm in diameter. Proximal diameters of 24, 26, 28, 30, 32 and 36 mm were chosen. RESULTS: Of the 439 plans, 372 standard juxtarenal (SJR) cases, defined by the inclusion of a scallop and 0, 1 or 2 small fenestrations (12%, 13% and 75% of the cases, respectively) were identified and used to test the applicability of the model. Mean CP (clock position) for right RA was 9:30, for the left RA 3:00, being a mean of 21 +/- 5 and 22 +/- 5 mm, respectively from the GE. RA CP was within the RFSG range in 86% (right) and 88% (left) of the cases, with 96% and 98%, respectively, within the allowable distance from the GE. A total of 81% of all SJR cases were potentially treatable using the RFSG model. CONCLUSIONS: An RFSG device would allow for the treatment of the majority of juxtarenal aortic aneurysms, which currently require custom-made devices. PMID- 20304685 TI - Exercise linked to transient increase in expression and activity of cation channels in newly formed hind-limb collaterals. AB - OBJECTIVE: This study aimed to compare arteriogenesis after femoral artery occlusion as influenced by exercise or arteriovenous shunt and follow changes in collateral transient receptor potential cation channel, subfamily V, member 4 (Trpv4). DESIGN: A prospective, controlled study wherein rats were subjected to femoral artery ligation (FAL), or FAL+arteriovenous shunt. Collateral Trpv4 was determined 0.5 and 6h post exercise. METHODS: Rats were subjected to exercise for 15 min, twice daily. The number and diameter of collaterals were assessed after 7 days. Collateral Trpv4 expression was quantified by reverse transcription polymerase chain reaction. RESULTS: Collateral number and diameter per limb were significantly higher in the shunt group (number: 16.0+/-2.4 and diameter: 216.0+/ 34 microm) compared to the ligature (number: 9.4+/-2 and diameter: 144+/-21 microm) and exercise groups (number: 9.9+/-2.5 and diameter: 151+/-15 microm). Trpv4 expression in collaterals harvested 0.5h post exercise was not significantly different from expression in shunted rats. It was significantly lower in collaterals harvested 6h post exercise (comparable to that in ligated rats). CONCLUSION: Collateral formation was greater in the shunt group than in the exercise group. Exercise-induced Trpv4 up-regulation, not significantly different from that achieved with shunt, returned to control values when evaluated 6h post exercise. More frequent exercise to chronically increase fluid shear stress, as with a shunt model, may be required for sufficient arteriogenesis to compensate for peripheral occlusion. PMID- 20304686 TI - Patterns of second-opinion diagnosis in oral and maxillofacial pathology. AB - OBJECTIVES: Several studies have documented the beneficial effect of second opinions in diagnostic pathology. Among disease sites, the head and neck can be a particularly problematic area for pathologists, prompting frequent second opinions. However, the effect of second opinion requests made by physician pathologists (PPs) to oral and maxillofacial pathologists (OMPs) has not been well studied and might identify disease and subsites that pose diagnostic challenges. The objectives of this study were to study the referral patterns of PPs to a referral center for oral and maxillofacial pathology and to assess changes in diagnosis following second opinion. STUDY DESIGN: We retrospectively reviewed 142 consecutive pathology consultation requests over a 2-year period. The submitted report and matched second opinion report were reviewed to extract predetermined demographic, clinical, and pathologic data. Each diagnosis was reviewed to determine if there was agreement, minor disagreement, or major disagreement between the original and the second opinion. RESULTS: The most common diagnostic categories sent for second opinion were dysplasia/carcinoma, odontogenic cysts, and odontogenic tumors. In the 135 cases where agreement could be assessed, there were a total of 46 cases (34.1%) with differences in diagnostic opinion. Minor disagreements occurred in 24 cases (17.8%) and major disagreements in 22 cases (16.3%). Importantly, major disagreements identified here would have resulted in significant differences in patient evaluation and management. CONCLUSIONS: This study supports the positive impact of second opinion surgical pathology for lesions in the maxillofacial complex and supports the role of OMPs in subspecialty diagnostic pathology. PMID- 20304688 TI - Transient receptor potential channels: emerging roles in health and disease. PMID- 20304687 TI - A histopathologic comparison between synchronous and single primary oral squamous cell carcinomas. AB - OBJECTIVE: This study compares synchronous oral squamous cell carcinomas (OSCCs) with single primary OSCCs to assess the histopathologic parameters with a known prognostic significance. STUDY DESIGN: Twenty-eight cases of synchronous OSCCs and a control group of single primary OSCCs were compared for 15 histologic prognostic variables. RESULTS: Results showed significantly less amount of abnormal mitoses (synchronous-1: P = .002; synchronous-2: P = .006) and tumor induced stroma (synchronous-1: P = .011; synchronous-2: P = .001) in synchronous OSCCs than in single primary OSCCs. Depth of invasion was considerably lower in synchronous OSCCs than in single primary OSCCs (synchronous-1: P = .007; synchronous-2: P = .002). Lymph node metastasis (synchronous-1: P = .051; synchronous-2: P = .051) was found to be rare in synchronous OSCCs compared with single primary OSCCs. CONCLUSION: Synchronous OSCCs show less aggressive histopathologic features than single primary OSCCs. PMID- 20304689 TI - Expression of muscarinic M1 and M2 receptors in the anterior cingulate cortex associated with neuropathic pain. AB - The anterior cingulate cortex (ACC) and muscarinic receptors modulate pain. This study investigates changes in the expression of muscarinic-1 and -2 receptors (M1R, M2R) in rats' ACC (cg1-rostral- and cg2-caudal) using a model of neuropathic pain by denervation, measured as autotomy score (AS) for 8 days. Changes were analysed with painful stimuli and with scopolamine into the ACC prior to this scheme. We used reverse transcriptase-polymerase chain reaction (RT PCR) and immunofluorescence to determine M1R and M2R's mRNA and protein levels, respectively. Animals were divided in low, medium and high AS groups. Cg1 showed decreased mRNA levels for both M1R and M2R in the low AS group, as opposed to an increased expression in the medium and high AS groups. Both receptors correlated positively with AS in these groups. In the scopolamine-treated animals there was an increase in mRNA levels for both receptors in cg1, whereas in cg2, mRNA levels of M1R decreased in all the AS and scopolamine groups. The increased M2R mRNA in cg2 correlated with AS in the low, medium and high AS groups whereas all the scopolamine groups showed an increase. Immunoreactivity of the M2R in cg1 decreased in the medium AS group in comparison to controls but scopolamine treatment produced an increase in the medium scopolamine AS group compared to the medium AS group. The M1R in cg1 and both receptors in cg2 showed no immunoreactivity changes. These results highlight the role of the M2R in cg1 related to the degree of autotomy. PMID- 20304690 TI - Bilateral Staphylococcus aureus sub-Tenon's abscess following strabismus surgery in a child. AB - Infection after strabismus surgery is rare. Here we describe a 5-year-old girl who developed bilateral staphylococcal sub-Tenon's abscess resistant to fourth generation fluoroquinolones that resolved completely after surgical drainage and irrigation with povidone iodine followed by administration of oral amoxicillin and clavulanic acid. A lost muscle required exploration and reattachment to the sclera. PMID- 20304691 TI - Specific monoclonal antibodies and ultrasensitive immunoassays for 20K and 22K human growth hormone. AB - OBJECTIVE: Generation of specific monoclonal antibodies (mAbs) against 20K and 22K human growth hormone (hGH) and development of ultrasensitive immunoassays to quantify 20K and 22K hGH. DESIGN: Mice were immunized with recombinant 20K or 22K hGH. Hybridoma cells were screened with biotinylated 20K and 22K hGH simultaneously. The specific mAbs were further characterized and used for construction of isoform specific assays. The ultrasensitive chemiluminescent assays were developed with AMDEX streptavidin-HRP and a sensitive substrate. RESULTS: The 20K hGH specific mAb 1G12 and the 22K hGH specific mAb 5E1 showed less than 0.1% cross-reactivity to 22K or 20K hGH by competitive binding assay, respectively. Western blot analysis also confirmed the specificity of mAb 1G12 and mAb 5E1. Using mAb 1G12 and mAb 5E1, 20K and 22K specific assays with working range of 2-2000 pg/mL were constructed. The 22K hGH concentrations in 103 serum samples from different healthy subjects in the basal GH state were 343.7+/-421.5 pg/mL (18.6-1820 pg/mL). The 20K hGH concentrations were 30.7+/-37.5 pg/mL (2.4 205pg/mL). The ratios of 20K to 20K plus 22K hGH were 9.8+/-4.4% (3.3-28.3%). Both 22K hGH and 20K hGH concentrations in women (465.9+/-476.3 pg/mL and 43.7+/ 46.1 pg/mL, n=47) were significantly higher than those (241.1+/-337.0 pg/mL and 20K hGH 19.8+/-23.0 pg/mL, n=56, P<0.01) in men. However, there was no difference in the proportion of 20K to 20K plus 22K between men and women (P>0.05). The strong correlation between 20K and 22K hGH (R=0.914, P<0.01) indicated the constant proportion between 20K and 22K hGH in the basal GH state of healthy subjects. CONCLUSIONS: Specific monoclonal antibodies and ultrasensitive chemiluminescent immunoassays for 20K and 22K hGH were generated. The ultrasensitive immunoassays are essential for the determination of 20K and 22K hGH in the basal GH state. This universal ultrasensitive immunoassay form can be adapted to other immunoassays for broad application. PMID- 20304692 TI - Creatine metabolism and the urea cycle. AB - Because creatine and creatine phosphate are irreversibly converted to creatinine, there is a continuous need for their replacement. This occurs by means of diet and de novo synthesis. Dietary creatine is provided in animal products and can amount to about half of the required amount. Synthesis provides the remainder. Creatine synthesis is a major component of arginine metabolism, amounting to more than 20% of the dietary intake of this amino acid. Creatine metabolism is of importance to patients with urea cycle disorders in two ways, both related to arginine levels. In patients with arginase deficiency, markedly elevated arginine levels may result in higher concentrations of guanidinoacetate and higher rates of creatine synthesis. This is of concern because it is thought that elevated levels of guanidinoacetate may exert neurotoxic effects. In the case of the other urea cycle disorders, arginine levels are markedly decreased unless the patients are supplemented with this amino acid. Decreased levels of arginine may result in decreased rates of creatine synthesis. This may be compounded by the fact that such patients, maintained on low protein diets, will also have lower dietary creatine intakes. There is some evidence that this may decrease brain creatine levels which may contribute to the neurological symptoms exhibited by these patients. It is clear that patients with urea cycle disorders also have altered creatine metabolism. Whether this contributes in a significant way to their neurological symptoms remains an open question. PMID- 20304693 TI - [Biomedical research, the market, clinicians, safety and corporate social responsibility post-phase III: maintaining confidence]. AB - INTRODUCTION: Randomised controlled trials (RCTs) are the gold standard in the western world for decision making, as much for the clinicians as for the agencies or managers for community policies. In this powerful deployment of investigative effort there are variable degrees of conflict of interests, and the clinicians, not foreign to this, are entering a sea of doubts on safety, a dimension that emerges like a diacritical, inalienable element. The aim of the study was to select and ctically evaluate editorials, clinical trials and/or meta-analyses published on physical support, or the more important internationally credited websites, which has patient safety as their primary objective. PATIENTS AND METHODS: Evaluative study performed in the Torrecardenas Hospital, of the Andalucian Public Health Service (SSPA), in the context of an accredited training unit (Mejora_F), so called "transference of the biomedical knowledge from the bibliography" from 2008 to 2009. RESULTS: Analyzed articles: 170 (75 % in English, with predominance of N Eng J Med >50 %; followed by Journal Of the American Medical Association, The Lancet, British Medical Journal, Journal of American Geriatrics; Med Clin, Rev Clin Esp.; and Infectologia). From 170 eligible articles we selected 5 key topoi due to their impact as the most representative owing to their citation frequency. They represented, in our judgment, "a red flag" of safety: long-acting beta-stimulators or LABS and increase in mortality in asthma; neuroleptics in the elderly and extension of the QT interval associated with sudden death; thiazolidinediones in type II diabetes and negative cardiovascular effects; promotion of statins-ezetimibe and the debatable association with major mortality for cancer, and intensive treatment in diabetes and probable increase in mortality. CONCLUSIONS: What really maters in biomedicine is that it leads to a given strategy in real patients, not the intermediate points. Clinicians should not support partial results of designs based on intermediate information - undoubtedly less costly and more rapid - without adequately knowing the safety of the strategy built to reach them. Only in this way we can be real guarantors of safety, and only in this way, and in absence of conflicts of interests we will be able to support the given confidence. PMID- 20304694 TI - Molecular characterization and susceptibility testing of Helicobacter pylori strains isolated in western Argentina. AB - OBJECTIVE: To characterize Helicobacter pylori isolates from western Argentina using virulence markers and antimicrobial susceptibility patterns in order to assess the association between virulent genotypes, antimicrobial resistance, and disease. DNA fingerprinting was also evaluated for the segregation of virulent or resistant strain clusters. METHODS: Genotyping of 299 H. pylori isolates was performed by PCR using specific primers for the cagA, vacA and iceA genes. Random amplification of polymorphic DNA (RAPD)-PCR and rep-PCR genetic clustering were assessed using five random primers and BOXA1R and ERIC primers, respectively. Resistance to clarithromycin (Cla) and metronidazole (Mtz) was assessed by the agar dilution method. RESULTS: It was observed that 40.8% of the genotypes were cagA-positive; 66.9% were vacA s1m1 genotype and the iceA1 allele was found in 40.8%. A significant correlation (p=0.0000) was observed between cagA positivity and vacA s1m1/iceA1 genotypes. Triple virulent genotypes were statistically associated with peptic ulcer (PU) (p=0.0001) and Cla resistance (p=0.0000). RAPD fingerprints obtained with AO2 primers identified clusters that were strongly associated with PU, virulence markers, and resistance to Cla and Mtz. CONCLUSIONS: The H. pylori isolates that harbored two or three virulence markers were more resistant to Cla and Mtz. Combined analysis of virulent genotypes and resistance patterns may permit identification of high-risk patients to prevent PU later in life or to avoid antimicrobial treatment failure. PMID- 20304695 TI - Familial 18 centromere variant resulting in difficulties in interpreting prenatal interphase FISH. AB - We report here on a familial case of centromeric heteromorphism of chromosome 18 detected by prenatal interphase fluorescence in situ hybridization (FISH) analysis transmitted by the mother to her fetus, and resulting in complete loss of one 18 signal. The prenatal diagnosis was performed by interphase FISH (AneuVysion probe set, and LSI DiGeorge 22q11.2 kit) because of the presence of an isolated fetal cardiac abnormality, and was first difficult to interpret: only one centromeric 18 signal was detectable on prenatal interphase nuclei, along with one signal for the Y and one for the X chromosome. The LSI DiGeorge 22q11.2 kit also showed the absence of one TUPLE 1 signal on all examined nuclei. In fact, the FISH performed on maternal buccal smear displayed the same absence of one chromosome 18 centromeric signal, combined with the presence of two TUPLE1 signals. All these results led to the diagnosis of an isolated 22q11.2 fetal microdeletion that was confirmed on metaphases spreads. This case illustrates once again that the locus specific (LSI) probes are more effective than the alpha centromeric probes for interphase analysis. The development of high-quality LSI probes for chromosomes 18, X and Y could avoid the misinterpretation of prenatal interphase FISH leading to numerous additional and expensive investigations. PMID- 20304696 TI - Two infant deaths linked to intussusception without peritonitis. AB - We report two infant deaths attributable to intussusception, but without clear evidence of peritonitis. In the first instance, a 3-year-old girl had presented with abdominal pain, vomiting, and melena before her demise. Aspirated vomitus was subsequently ascertained as the immediate cause of death, due to intussusception-induced ileus. The other infant, a 2-month-old male, showed autopsy evidence of intussusception at two sites, with likely aspiration of gastric mucus. Since the circumstances surrounding his death were vague, timing of the intussusception was difficult to pinpoint. Thus, an inconsequential, agonal event could not be discounted. Taken together, however, death from intussusception, without peritonitis, is the most viable postmortem interpretation for both patients. The causes of death in such cases are established by comprehensive delineation of preceding clinical events, plus autopsy documentation of coexistent intussusception and vomitus aspiration. PMID- 20304697 TI - Sonochemical synthesis of Dy2(CO3)3 nanoparticles, Dy(OH)3 nanotubes and their conversion to Dy2O3 nanoparticles. AB - Dysprosium carbonates nanoparticles were synthesized by the reaction of dysprosium acetate and NaHCO(3) by a sonochemical method. Dysprosium oxide nanoparticles with average size about 17 nm were prepared from calcination of Dy(2)(CO(3))(3).1.7H(2)O nanoparticles. Dy(OH)(3) nanotubes were synthesized by sonication of Dy(OAC)(3).6H(2)O and N(2)H(4). The as-synthesized nanostructures were characterized by scanning electron microscopy (SEM), X-ray powder diffraction (XRD), transmission electron microscopy (TEM), and Fourier transform infrared spectroscopy (FT-IR). Photoluminescence measurement shows that the nanoparticles have two emission peaks around 17,540 cm(-1) and 20,700 cm(-1), which should come from the electron transition from (4)F(9)(/)(2)- >(6)H(15)(/)(2) levels and (4)F(9)(/)(2)-->(6)H(13)(/)(2) levels, respectively. The effect of calcination temperature and sonication time was investigated on the morphology and particle size of the products. The sizes could be controlled by the feeding rate of the precipitating agent (NaHCO(3) and N(2)H(4)) and slower feeding rate lead to smaller nanoparticles. PMID- 20304698 TI - Constitutive formulation and analysis of heel pad tissues mechanics. AB - This paper presents a visco-hyperelastic constitutive model developed to describe the biomechanical response of heel pad tissues. The model takes into account the typical features of the mechanical response such as large displacement, strain phenomena, and non-linear elasticity together with time-dependent effects. The constitutive model was formulated, starting from the analysis of the complex structural and micro-structural configuration of the tissues, to evaluate the relationship between tissue histology and mechanical properties. To define the constitutive model, experimental data from mechanical tests were analyzed. To obtain information about the mechanical response of the tissue so that the constitutive parameters could be established, data from both in vitro and in vivo tests were investigated. Specifically, the first evaluation of the constitutive parameters was performed by a coupled deterministic and stochastic optimization method, accounting for data from in vitro tests. The comparison of constitutive model results and experimental data confirmed the model's capability to describe the compression behaviour of the heel pad tissues, regarding both constant strain rate and stress relaxation tests. Based on the data from additional experimental tests, some of the constitutive parameters were modified in order to interpret the in vivo mechanical response of the heel pad tissues. This approach made it possible to interpret the actual mechanical function of the tissues. PMID- 20304699 TI - Polymorphisms of caffeine metabolism and estrogen receptor genes and risk of Parkinson's disease in men and women. AB - Caffeine intake has been associated with a decreased risk of Parkinson's disease (PD) in men but the effect in women is less clear, and appears to be modified by use of post-menopausal estrogens. In a nested case-control study within the Nurses Health Study (NHS) and the Health Professionals Follow-up Study (HPFS), we examined associations between single nucleotide polymorphisms (SNPs) of caffeine metabolizing genes (CYP1A2 and NAT2) and estrogen receptors (ESR1 and ESR2), their interaction with caffeine intake and hormone replacement therapy (PMH) use (collected prospectively) and risk of PD. We matched 159 female cases to 724 controls and 139 male cases to 561 controls on birth year, source of DNA (blood or buccal smear), age and sex. The CYP1A2 rs762551 polymorphism (lower enzyme inducibility) was marginally associated with an increased risk of PD (RR, for increasing number of minor alleles=1.34; 95% CI 1.02, 1.78 in women, but not in men. None of the NAT2 (classified as slow vs. fast acetylator), ESR1 or ESR2 polymorphisms were significantly associated with an altered risk of PD. Marginally significant interactions were observed between caffeine intake and the ESR1 polymorphism rs3798577 (p=0.07) and ESR2 polymorphism rs1255998 (p=0.07). The observed increased risk of PD among female but not male carriers of the rs762551 polymorphism of CYP1A2 and the interactions of caffeine with ESR1 rs3798577 and ESR2 rs1255998 may provide clues to explain the relationship between gender, caffeine intake, estrogen status and risk of PD and need to be replicated. PMID- 20304700 TI - Optimizing care of residents with Parkinsonism in supervised facilities. AB - People with Parkinsonism (PWP) in residential facilities are usually elderly, cognitively impaired, physically disabled with poor quality of life and a high mortality rate. This paper aims to determine if the care of PWP in residential facilities could be improved by addressing staff knowledge on Parkinson related issues. A curriculum based on the Victorian Comprehensive Parkinson Program (VCPP) was developed and delivered to 118 staff members in 9 facilities across Melbourne. Measures of staff knowledge were undertaken at baseline, 1, 3 and 12 months. Data from a total of 49 residents were used in the analysis. Measures were taken at baseline, 1, 3 and 12 months included dementia screen (MMSE), geriatric depression scale (GDS), quality of life (PDQ39), fatigue (PDFS16), monthly falls diary, Unified Parkinson Disease Rating Scale (I,II,III) Hoehn & Yahr scale (H&Y) and resident/family questionnaire (RFQ) which focused on quality of care provision. It was found that the staff knowledge assessment scores (max = 37) significantly improved post education (P < 0.01) from baseline mean (11.1) and were maintained to 12 months mean (29.0). The residents group improved significantly for all measures at 1 month and these improvements were maintained up to 12 months (except for UPDRS III). This study demonstrated how a simple intervention, resulting in improved staff knowledge, produced a significant and clinically meaningful improvement in the care of PWP. PMID- 20304701 TI - WRKY transcription factors. AB - WRKY transcription factors are one of the largest families of transcriptional regulators in plants and form integral parts of signalling webs that modulate many plant processes. Here, we review recent significant progress in WRKY transcription factor research. New findings illustrate that WRKY proteins often act as repressors as well as activators, and that members of the family play roles in both the repression and de-repression of important plant processes. Furthermore, it is becoming clear that a single WRKY transcription factor might be involved in regulating several seemingly disparate processes. Mechanisms of signalling and transcriptional regulation are being dissected, uncovering WRKY protein functions via interactions with a diverse array of protein partners, including MAP kinases, MAP kinase kinases, 14-3-3 proteins, calmodulin, histone deacetylases, resistance proteins and other WRKY transcription factors. WRKY genes exhibit extensive autoregulation and cross-regulation that facilitates transcriptional reprogramming in a dynamic web with built-in redundancy. PMID- 20304702 TI - Lung cancer in never smokers: a new hot area of research. PMID- 20304704 TI - Proteomic approaches in the search for biomarkers of liver fibrosis. AB - Chronic liver diseases (CLDs) can cause progressive hepatic fibrosis culminating in cirrhosis. Fibrosis staging requires liver biopsy, which is invasive, expensive and frequently poorly tolerated by patients. Serum-based panels of fibrosis biomarkers have been developed as alternatives to biopsy. Recent advances in high-throughput proteomic methods have the potential to optimise combinations of biomarkers for the diagnosis of liver fibrosis. Here, we review the key recent developments in the field of proteomics and their application to this important clinical question. We critically discuss the challenges and priorities for future research that are of critical importance to clinical hepatology. PMID- 20304703 TI - Genetic variants and risk of lung cancer in never smokers: a genome-wide association study. AB - BACKGROUND: Lung cancer in individuals who have never smoked tobacco products is an increasing medical and public-health issue. We aimed to unravel the genetic basis of lung cancer in never smokers. METHODS: We did a four-stage investigation. First, a genome-wide association study of single nucleotide polymorphisms (SNPs) was done with 754 never smokers (377 matched case-control pairs at Mayo Clinic, Rochester, MN, USA). Second, the top candidate SNPs from the first study were validated in two independent studies among 735 (MD Anderson Cancer Center, Houston, TX, USA) and 253 (Harvard University, Boston, MA, USA) never smokers. Third, further replication of the top SNP was done in 530 never smokers (UCLA, Los Angeles, CA, USA). Fourth, expression quantitative trait loci (eQTL) and gene-expression differences were analysed to further elucidate the causal relation between the validated SNPs and the risk of lung cancer in never smokers. FINDINGS: 44 top candidate SNPs were identified that might alter the risk of lung cancer in never smokers. rs2352028 at chromosome 13q31.3 was subsequently replicated with an additive genetic model in the four independent studies, with a combined odds ratio of 1.46 (95% CI 1.26-1.70, p=5.94x10(-6)). A cis eQTL analysis showed there was a strong correlation between genotypes of the replicated SNPs and the transcription level of the gene GPC5 in normal lung tissues (p=1.96x10(-4)), with the high-risk allele linked with lower expression. Additionally, the transcription level of GPC5 in normal lung tissue was twice that detected in matched lung adenocarcinoma tissue (p=6.75x10(-11)). INTERPRETATION: Genetic variants at 13q31.3 alter the expression of GPC5, and are associated with susceptibility to lung cancer in never smokers. Downregulation of GPC5 might contribute to the development of lung cancer in never smokers. FUNDING: US National Institutes of Health; Mayo Foundation. PMID- 20304705 TI - Antitumour and immune-adjuvant activities of protein-tyrosine kinase inhibitors. AB - The immunologic approach to tumour therapy is hampered by the development of direct immune escape mechanisms and the induction of an immunosuppressive tumour microenvironment characterised by the expansion of myeloid-derived suppressor cells (MDSCs) and tumour-specific regulatory T cells (Tregs). The implementation of inhibitors targeting protein tyrosine kinases, which are involved in the process of tumour development and angiogenesis, has produced robust clinical responses. The consequences of these compounds on the functionality of immune effector cells have been investigated. This review summarises recent reports on the direct and indirect effects of protein tyrosine kinase inhibitors (TKIs) on the immune system and discusses the application of immunotherapeutic strategies in combination with these inhibitors to improve the efficacy of immune-based therapies. PMID- 20304706 TI - Monitoring antimalarial resistance: launching a cooperative effort. AB - Current information on efficacy of antimalarials is crucial to provide early warning of resistance. A collaborative effort between the Global Malaria Program of the World Health Organization (WHO) and the WorldWide Antimalarial Resistance Network (WWARN) has recently been launched. The effort is planned as a collaboration with the scientific malaria community to create a global, comprehensive, and inclusive network that will provide quality-assured information on antimalarial drug resistance. PMID- 20304707 TI - A changing environment and the epidemiology of tsetse-transmitted livestock trypanosomiasis. AB - The distribution, prevalence and impact of vector-borne diseases are often affected by anthropogenic environmental changes that alter the interactions between the host, the parasite and the vector. In the case of tsetse-transmitted livestock trypanosomiasis these changes are a result of the encroachment of people and their livestock into tsetse-infected wild areas. This has created a sequence of new epidemiological settings that is changing the relative importance of the domestic or sylvatic trypanosome transmission cycles and is causing concomitant changes in the impact of the disease on livestock. These changes in the dynamics of the epidemiology have an important impact on the factors that need to be considered when developing area-specific strategies for the future management of tsetse-transmitted livestock trypanosomiasis. PMID- 20304708 TI - Acupuncture and heart rate variability: a systematic review. AB - Acupuncture has been reported to affect the autonomic system. Currently, there are no systematic reviews examining the effect of acupuncture on HRV available in the literature. Therefore, the aim of this systematic review was to summarize and critically assess the effects of acupuncture on heart rate variability. We searched the literature using 14 databases for articles published from the earliest available publications until October 2009 without language restrictions. We included randomized clinical trials (RCTs) comparing acupuncture and sham acupuncture. The risk of bias in each study was assessed using the Cochrane criteria. Twelve RCTs met all of the inclusion criteria. One RCT evaluated the effects of acupuncture in patients with minor depression or anxiety disorders and another RCT examined the effect of acupuncture on migraine patients. Another four RCTs tested the effects of acupuncture in healthy subjects who were exposed to several conditions, including mental stress, fatigue from driving, and caffeine intake. The remaining six RCTs assessed the effects of acupuncture on healthy subjects in a normal state without any stressors. Five RCTs found significant differences in HRV between patients treated with acupuncture versus those treated with sham acupuncture (controls). However, the majority of the other RCTs showed inconsistent results or did not identify significant differences in HRV spectral parameters among individuals treated with acupuncture as compared to those treated with sham acupuncture. In conclusion, sham-controlled RCTs showed variable results and no clear evidence that acupuncture has any specific effects on HRV. Therefore, more rigorous research appears to be warranted. PMID- 20304709 TI - Electrochemistry of interaction of 2-(2-nitrophenyl)-benzimidazole derivatives with DNA. AB - In this study the interaction between new benzimidazole molecules, 2-(2 nitrophenyl)-1H-benzimidazole (NB) and N-benzoyl-2-(2-nitrophenyl)-benzimidazole (BNB), with dsDNA and ssDNA was assessed at pH 7.4. Using differential pulse voltammetry at glassy carbon electrode, both molecules were electrochemically reduced due to the presence of a nitro group in their structures. When DNA was added to the solution, the electrochemical signal of NB and BNB decreased and shifted to more negative potentials. The interaction mode was electrostatic when ionic strength was low. Under this condition DNA-nitro complexes were characterized and binding constant values of 8.22 x 10(4)M(-1) and 3.08 x 10(6)M( 1) for NB and BNB with dsDNA were determined. On the other hand, only NB was able to interact when a high concentration of NaCl was used. Finally, a glassy carbon electrode modified with carbon nanotubes and DNA was tested in order to determine the nitrocompound in solution. The electrochemical reduction of the nitrocompound adsorbed on GCE/CHIT-CNT/DNA was used as an analytical signal. Using 10 min as accumulation time, a linear dependence was observed between 20 and 80 microM nitrocompound concentrations and the electrode response. Detection and quantification limits in the range of microM were determined. PMID- 20304710 TI - [Age of menopause in patients with differentiated thyroid cancer treated with radioiodine]. AB - INTRODUCTION: Differentiated thyroid cancer (DTC) is an increasingly frequent endocrinological disease. Radioiodine is a key component of treatment. OBJECTIVE: To analyze the effects of I(131) therapy on ovarian and reproductive function. MATERIAL AND METHODS: We retrospectively analyzed data from 202 women treated with radioiodine for DTC in our service from 1985-2008. Data on age at menopause in patients and their mothers and sisters, menstrual history, fertility and neonatal abnormalities were collected. RESULTS: Menopause occurred in 34 patients at follow-up. The mean age at menopause in patients was 49.94+/-3.45 while that in their mothers and sisters was 49.20+/-5.37 and 48.73+/-3.74 years, respectively. Three patients had transient amenorrhea. No infertility or neonatal alterations were found. CONCLUSIONS: In our series, menopause did not occur earlier in patients than in their first degree relatives. No significant alterations in neonatal health, fertility or menstruation were found. PMID- 20304711 TI - Introduction to the Mini-Symposium on non-alcoholic fatty liver disease. PMID- 20304712 TI - Tricophytic or pre-trichophytic closure? PMID- 20304713 TI - Innovative treatment for huge nuchal desmoid tumour: a case report with a 2-year follow-up. AB - BACKGROUND: The desmoid tumour is a monoclonal neoplasm originating from musculoaponeurotic tissues. It is benign in histological presentations and yet its locally invasive behaviour could lead to dire consequences such as disfigurement, functional impairment or even mortality. Surgical resection, radiotherapy, chemotherapy, hormonal therapy, non-steroidal anti-inflammatory drugs and even a wait-and-see policy, either alone or in combination, were advocated as treatment modalities. We experienced an extremely difficult case who had a huge nuchal desmoid tumour measuring 45x35x20 cm in dimension with extension to the anterior neck and thoracic paraspinal area. Its intimacy with the carotid artery, jugular vein and brachial plexus made margin-free resection infeasible. Moreover, the tumour burden was so immense that the patient was plunged into profound hypoproteinaemic, septic and anaemic status, with severe pain, bleeding and odour that mandated prompt and daring management. METHODS: In an effort to prevent uncontrollable tumour bleeding, we embarked on a series of strategic measures, including pre-surgical embolisation, innovative tourniquet technique, a novel method of ligature deployment, staged tumour excision and adjunct methods, such as ethanol injection and irradiation therapy. RESULTS: The huge nuchal desmoid tumour was successfully excised under the planned strategies. The patient went through a number of complications such as sepsis, acute respiratory distress and renal failure. Fortunately, she eventually survived and exhibited no evidences of tumour relapse at 2 years' follow-up. She has resumed daily activity independently without noticeable functional deficit. CONCLUSION: We believe that multimodality strategies and innovative surgical techniques are the key to success in managing such a difficult case. PMID- 20304714 TI - A new alternative for reconstruction of soft triangle defects secondary to burn injury: superiorly based columellar flap. AB - Nasal reconstruction following severe burn injury remains a challenge in plastic surgery. In burn patients, the external nares and the soft triangle are commonly affected subunits of the nose where local tissue deficit and scar contraction during the recovery period contribute to soft triangle deformity and alar stenosis. These patients usually have associated facial burns with varying severity, which significantly limit the availability of local flaps. Reconstruction with skin grafts often yields unsatisfactory results because of the mismatch in colour and texture in addition to the primary and secondary contraction phenomena. The use of superiorly based columellar flap, which has yielded satisfactory results on a female patient, would be a new and reliable option for reconstruction of the soft triangle deficit with alar stenosis. PMID- 20304715 TI - Print news coverage of cancer: what prevention messages are conveyed when screening is newsworthy? AB - BACKGROUND: Americans are generally favorable towards cancer screening, but fatalistic about cancer prevention. News coverage shapes perceptions of cancer control in meaningful ways, but there is little consensus as to the impact of news on our understanding of and engagement in cancer screening practices. Our analysis of cancer screening-related print news coverage during a four month period in 2005 suggests that the newsworthiness of new screening technologies may undermine public confidence in currently available and effective secondary prevention programs, while promoting tests whose effectiveness is debated or not yet established. METHODS AND RESULTS: We conducted a structured text analysis of 517 cancer-related news articles from 15 leading daily newspapers and a subsequent qualitative analysis of the 79 screening news articles. Screening articles were analyzed for content related to criteria for screening effectiveness. Content patterns for each type of screening and cancer were also noted. News coverage consistently conveyed screening as important and highlighted the need to protect and expand access to screening. At the same time, to the extent that story content was framed by the newsworthiness of new tests and technologies this often indirectly called into question effective and established protocols and programs without providing any actionable alternative. CONCLUSION: This analysis revealed unexpected messages about screening that are potentially problematic for cancer control. The cancer control community should continue efforts to understand and shape news coverage of screening in order to promote balanced and action-oriented content. Research has shown that Americans hold conflicting views regarding cancer-having a favorable opinion of screening while simultaneously feeling fatalistic about prevention. Our analysis of print news stories on cancer screening suggests that the determination of screening's "newsworthiness" is related to newly developed tests and protocols, which may create demand for new tests whose effectiveness is unknown and undermine confidence in established and effective screening programs. PMID- 20304716 TI - ["Dose tolerance" in radiotherapy--development and foundations]. PMID- 20304717 TI - [A comparison of Monte-Carlo simulated and measured dose distributions in oblique electron beams]. AB - Oblique incidence of electron beams is a rare clinical application which can be used e.g. at the irradiation of the internal mammary lymph nodes in the case of mamma carcinoma. 3-D treatment planning systems are accepted standard for photon beams but not for electron beams. The investment for measuring, implementing and testing basic data seems many customers not to be worthwhile when considering the well known inaccuracies of conventional algorithms. From Monte-Carlo (MC) based algorithms however higher accuracies can be expected. It was the aim of this paper to test the MC algorithm of the treatment planning system Oncentra Treatment Planning (OTP, Theranostic) in the application for oblique incidence of electron beams. Measured and simulated values are compared for electron energies from 4 MeV up to 18 MeV. For standard electron applicators, even at extended source-surface distances, satisfying results are achieved. However, the agreement gets lost with increasing oblique incidence, especially for small individual and asymmetrical cut outs. We therefore still use measured values instead of simulated dose distributions. PMID- 20304718 TI - [Analysis of flow in artificial stenosis models of mid-sized arteries using 3D PC MRI]. AB - Phase contrast MRI allows access to tri-directional encoded velocity information and therefore, measurement of flow in the human hemodynamic system. The aim of this work was to investigate whether this technology could be applied to support the grading of stenosis in mid-size arteries. Using a specially constructed flow phantom and a stenosis model with tube diameter of 5mm and 8mm and a stenosis of 50%, experiments at different flow rates (180-640 ml/min), slice thickness (1-4 mm), field strength (1.5 and 3.0 T), and multi-slice as well as 3D volume acquisition were performed. The observations were assessed visually and evaluated by signal-to-noise (SNR) ratios in regions before and after the stenosis. The obtained results show that examinations should be performed at high field (3.0 T) and at flow rates up to 500 ml/min without hampering the measurements by areas of signal loss. In comparison, no detectable differences in the flow patterns of the two acquisition schemes could be observed. However, the SNR was higher using the 3D volume acquisition and thick slices. In summary, 3D PC-MRI of mid-size vessels with stenosis is feasible for certain flow rates. The presented results could be seen as guidance for in vivo situations to assess if an examination of a patient is reasonable in terms of outcome. PMID- 20304719 TI - [Quality control in PET/CT systems: experiences and requirements]. AB - Today, in most cases PET examinations are performed using PET/CT hybrid systems. While acceptance testing and routine control of the basic modalities PET and CT, respectively, are described by appropriate regulations, corresponding instructions with regard to the interface connecting both are still missing. This interface includes the adjustment of gantries and patient bed to each other as well as the energy scaling of attenuation coefficients from CT energy to 511 keV. Measurements checking the mechanical adjustment (determination of off-set parameters) are performed following manufacturer's recommendation, with a typical frequency twice a year. On a Biograph 16 (Siemens, Inc.), these measurements were systematically extended to a weekly frequency over an observation period of 10 months, supplemented by measurements with additional load to the patient bed (up to 135 kg), and different vertical bed positions. The results show, that for the construction tested additional off-set measurements for routine control extending well beyond manufacturer's recommendation are not necessary. The energy scaling of attenuation coefficients is depending on methodological aspects and software implementation, and therefore is not part of routine control. On the contrary, the development of appropriate methods for acceptance testing to assess and to determine the mechanical adjustment in all its degrees of freedom as well as the accuracy of attenuation corrected emission data is urgently needed. PMID- 20304720 TI - Shortest path refinement for motion estimation from tagged MR images. AB - Magnetic resonance tagging makes it possible to measure the motion of tissues such as muscles in the heart and tongue. The harmonic phase (HARP) method largely automates the process of tracking points within tagged MR images, permitting many motion properties to be computed. However, HARP tracking can yield erroneous motion estimates due to 1) large deformations between image frames, 2) through plane motion, and 3) tissue boundaries. Methods that incorporate the spatial continuity of motion--so-called refinement or flood-filling methods--have previously been reported to reduce tracking errors. This paper presents a new refinement method based on shortest path computations. The method uses a graph representation of the image and seeks an optimal tracking order from a specified seed to each point in the image by solving a single source shortest path problem. This minimizes the potential errors for those path dependent solutions that are found in other refinement methods. In addition to this, tracking in the presence of through-plane motion is improved by introducing synthetic tags at the reference time (when the tissue is not deformed). Experimental results on both tongue and cardiac images show that the proposed method can track the whole tissue more robustly and is also computationally efficient. PMID- 20304721 TI - Generalized q-sampling imaging. AB - Based on the Fourier transform relation between diffusion magnetic resonance (MR) signals and the underlying diffusion displacement, a new relation is derived to estimate the spin distribution function (SDF) directly from diffusion MR signals. This relation leads to an imaging method called generalized q-sampling imaging (GQI), which can obtain the SDF from the shell sampling scheme used in q-ball imaging (QBI) or the grid sampling scheme used in diffusion spectrum imaging (DSI). The accuracy of GQI was evaluated by a simulation study and an in vivo experiment in comparison with QBI and DSI. The simulation results showed that the accuracy of GQI was comparable to that of QBI and DSI. The simulation study of GQI also showed that an anisotropy index, named quantitative anisotropy, was correlated with the volume fraction of the resolved fiber component. The in vivo images of GQI demonstrated that SDF patterns were similar to the ODFs reconstructed by QBI or DSI. The tractography generated from GQI was also similar to those generated from QBI and DSI. In conclusion, the proposed GQI method can be applied to grid or shell sampling schemes and can provide directional and quantitative information about the crossing fibers. PMID- 20304723 TI - A new optical-CT apparatus for 3-D radiotherapy dosimetry: is free space scanning feasible? AB - In this paper, we present a new optical computed tomography (Optical-CT) scanner for the verification of the radiation dose schemes delivered in modern radiotherapy applications. The optical-CT scanner is capable of providing rapid relative 3-D dosimetry with high spatial resolution with the use of normoxic N Vinylpyrrolidone based polymer gel dosimeter. The scanner employs a diffuse uncollimated light illumination beam, a computer controlled motorized rotation stage and a charge-coupled device (CCD) camera. Various test experiments were performed to determine the performance characteristics of the optical-CT apparatus. Attenuation coefficient (micro) versus dose calibration data were generated from two calibration experiments using gel containers of two different diameters. All irradiations were performed using a 6 MV linear accelerator. A comparison of the reconstructed images between optical-CT scans using refractive index (RI) matching fluid and corresponding scans performed in free space was demonstrated. The dose readout of a test irradiation model was found to be in good agreement with independent readout performed by MR imaging. The findings presented in this study suggest that polymer dosimeters combined with the new optical-CT scanner constitute a potentially feasible method capable of measuring complex 3-D dose distributions with high resolution and in a wide dose range. PMID- 20304722 TI - Multiplexed analysis of proteins in tissue using multispectral fluorescence imaging. AB - We present a new application of multispectral analysis for subcellular measurement of multiple proteins in formalin-fixed paraffin embedded tissue and cells. Typically, the targets of interest are present in the same or spatially overlapping cellular compartments. Such co-localization can complicate analysis and interpretation of the images obtained using traditional fluorescence, especially when spectrally overlapping labels are present. The spectral properties of currently available fluorescent dyes set an upper limit to the number of molecules that can be detected simultaneously with traditional fluorescence. By exciting a set of fluorophores at the same wavelength and unmixing their emission signals from background autofluorescence, we were able to image three targets in a single channel. This parallel imaging approach provides significant advantages for multiplexed analysis of tissues and cells. PMID- 20304724 TI - Automatic segmentation of pulmonary lobes robust against incomplete fissures. AB - A method for automatic segmentation of pulmonary lobes from computed tomography (CT) scans is presented that is robust against incomplete fissures. The method is based on a multiatlas approach in which existing lobar segmentations are deformed to test scans in which the fissures, the lungs, and the bronchial tree have been automatically segmented. The key element of our method is a cost function that exploits information from fissures, lung borders, and bronchial tree in an effective way, such that less reliable information (lungs, airways) is only used when the most reliable information (fissures) is missing. To cope with the anatomical variation in lobe shape, an atlas selection mechanism is introduced. The method is evaluated on two test sets of 120 scans in total. The results show that the lobe segmentation closely follows the fissures when they are present. In a simulated experiment in which parts of complete fissures are removed, the robustness of the method against different levels of incomplete fissures is shown. When the fissures are incomplete, an observer study shows agreement of the automatically determined lobe borders with a radiologist for 81% of the lobe borders on average. PMID- 20304725 TI - Fast semi-analytical model-based acoustic inversion for quantitative optoacoustic tomography. AB - We present a fast model-based inversion algorithm for quantitative 2-D and 3-D optoacoustic tomography. The algorithm is based on an accurate and efficient forward model, which eliminates the need for regularization in the inversion process while providing modeling flexibility essential for quantitative image formation. The resulting image-reconstruction method eliminates stability problems encountered in previously published model-based techniques and, thus, enables performing image reconstruction in real time. Our model-based framework offers a generalization of the forward solution to more comprehensive optoacoustic propagation models, such as including detector frequency response, without changing the inversion procedure. The reconstruction speed and other algorithmic performances are demonstrated using numerical simulation studies and experimentally on tissue-mimicking optically heterogeneous phantoms and small animals. In the experimental examples, the model-based reconstructions manifested correctly the effect of light attenuation through the objects and did not suffer from the artifacts which usually afflict the commonly used filtered backprojection algorithms, such as negative absorption values. PMID- 20304726 TI - A statistical framework for optimal design matrix generation with application to fMRI. AB - The general linear model (GLM) is a well established tool for analyzing functional magnetic resonance imaging (fMRI) data. Most fMRI analyses via GLM proceed in a massively univariate fashion where the same design matrix is used for analyzing data from each voxel. A major limitation of this approach is the locally varying nature of signals of interest as well as associated confounds. This local variability results in a potentially large bias and uncontrolled increase in variance for the contrast of interest. The main contributions of this paper are two fold: 1) we develop a statistical framework that enables estimation of an optimal design matrix while explicitly controlling the bias variance decomposition over a set of potential design matrices and 2) we develop and validate a numerical algorithm for computing optimal design matrices for general fMRI data sets. The implications of this framework include the ability to match optimally the magnitude of underlying signals to their true magnitudes while also matching the "null" signals to zero size thereby optimizing both the sensitivity and specificity of signal detection. By enabling the capture of multiple profiles of interest using a single contrast (as opposed to an F-test) in a way that optimizes for both bias and variance enables the passing of first level parameter estimates and their variances to the higher level for group analysis which is not possible using F-tests. We demonstrate the application of this approach to in vivo pharmacological fMRI data capturing the acute response to a drug infusion, to task-evoked, block design fMRI and to the estimation of a haemodynamic response function (HRF) in event-related fMRI. Although developed with motivation from fMRI, our framework is quite general and has potentially wide applicability to a variety of disciplines. PMID- 20304727 TI - A Bayesian mixture approach to modeling spatial activation patterns in multisite fMRI data. AB - We propose a probabilistic model for analyzing spatial activation patterns in multiple functional magnetic resonance imaging (fMRI) activation images such as repeated observations on an individual or images from different individuals in a clinical study. Instead of taking the traditional approach of voxel-by-voxel analysis, we directly model the shape of activation patterns by representing each activation cluster in an image as a Gaussian-shaped surface. We assume that there is an unknown true template pattern and that each observed image is a noisy realization of this template. We model an individual image using a mixture of experts model with each component representing a spatial activation cluster. Taking a nonparametric Bayesian approach, we use a hierarchical Dirichlet process to extract common activation clusters from multiple images and estimate the number of such clusters automatically. We further extend the model by adding random effects to the shape parameters to allow for image-specific variation in the activation patterns. Using a Bayesian framework, we learn the shape parameters for both image-level activation patterns and the template for the set of images by sampling from the posterior distribution of the parameters. We demonstrate our model on a dataset collected in a large multisite fMRI study. PMID- 20304728 TI - F-TIMER: fast tensor image morphing for elastic registration. AB - We propose a novel diffusion tensor imaging (DTI) registration algorithm, called fast tensor image morphing for elastic registration (F-TIMER). F-TIMER leverages multiscale tensor regional distributions and local boundaries for hierarchically driving deformable matching of tensor image volumes. Registration is achieved by utilizing a set of automatically determined structural landmarks, via solving a soft correspondence problem. Based on the estimated correspondences, thin-plate splines are employed to generate a smooth, topology preserving, and dense transformation, and to avoid arbitrary mapping of nonlandmark voxels. To mitigate the problem of local minima, which is common in the estimation of high dimensional transformations, we employ a hierarchical strategy where a small subset of voxels with more distinctive attribute vectors are first deployed as landmarks to estimate a relatively robust low-degrees-of-freedom transformation. As the registration progresses, an increasing number of voxels are permitted to participate in refining the correspondence matching. A scheme as such allows less conservative progression of the correspondence matching towards the optimal solution, and hence results in a faster matching speed. Compared with its predecessor TIMER, which has been shown to outperform state-of-the-art algorithms, experimental results indicate that F-TIMER is capable of achieving comparable accuracy at only a fraction of the computation cost. PMID- 20304729 TI - General retinal vessel segmentation using regularization-based multiconcavity modeling. AB - Detecting blood vessels in retinal images with the presence of bright and dark lesions is a challenging unsolved problem. In this paper, a novel multiconcavity modeling approach is proposed to handle both healthy and unhealthy retinas simultaneously. The differentiable concavity measure is proposed to handle bright lesions in a perceptive space. The line-shape concavity measure is proposed to remove dark lesions which have an intensity structure different from the line shaped vessels in a retina. The locally normalized concavity measure is designed to deal with unevenly distributed noise due to the spherical intensity variation in a retinal image. These concavity measures are combined together according to their statistical distributions to detect vessels in general retinal images. Very encouraging experimental results demonstrate that the proposed method consistently yields the best performance over existing state-of-the-art methods on the abnormal retinas and its accuracy outperforms the human observer, which has not been achieved by any of the state-of-the-art benchmark methods. Most importantly, unlike existing methods, the proposed method shows very attractive performances not only on healthy retinas but also on a mixture of healthy and pathological retinas. PMID- 20304730 TI - MRI pulse sequence design with first-order gradient moment nulling in arbitrary directions by solving a polynomial program. AB - We suggest a polynomial program for the calculation of optimized gradient waveforms for magnetic resonance tomography pulse sequences. Such non-linear mathematical programs can describe gradient system capabilities, meet k-space trajectory specifications, and capture sequence timing conditions. Moreover they allow the incorporation of gradient moment nulling constraints in one or several arbitrary spatial directions, which can reduce flow motion artifacts in the images. We report first experiences in solving such automatic pulse sequence design programs with the interior point solver Ipopt. PMID- 20304731 TI - Basic properties of SS-PARSE parameter estimates. AB - Single shot parameter assessment by retrieval from signal encoding (SS-PARSE) is a recently introduced method to obtain quantitative parameter maps from a single shot (typically 65 ms) magnetic resonance imaging (MRI) signal. Because it explicitly models local magnetization decay and phase evolution occurring during the signal 1) it can provide quantitative estimates of local transverse magnetization magnitude and phase, frequency, and relaxation rate and 2) it is free of geometric distortion or blurring due to field nonuniformities within the tissues. These properties promise to be advantageous in functional brain MRI (fMRI) and other dynamic imaging applications. In this paper, the basic phenomena underlying the performance of SS-PARSE in practice are discussed. Basic sources of bias errors in the parameter estimates are discussed, and performance of the method is characterized in terms of parameter estimates from simulation, experimental phantoms, and in vivo studies. Characteristics of the sum-of-square error cost function and the iterative search algorithm are discussed, and their relative roles in determining estimation accuracy are described. Practical guidelines for use of the method are presented and discussed. In vivo parameter maps are also presented. PMID- 20304732 TI - Registration of 4D cardiac CT sequences under trajectory constraints with multichannel diffeomorphic demons. AB - We propose a framework for the nonlinear spatiotemporal registration of 4D time series of images based on the Diffeomorphic Demons (DD) algorithm. In this framework, the 4D spatiotemporal registration is decoupled into a 4D temporal registration, defined as mapping physiological states, and a 4D spatial registration, defined as mapping trajectories of physical points. Our contribution focuses more specifically on the 4D spatial registration that should be consistent over time as opposed to 3D registration that solely aims at mapping homologous points at a given time-point. First, we estimate in each sequence the motion displacement field, which is a dense representation of the point trajectories we want to register. Then, we perform simultaneously 3D registrations of corresponding time-points with the constraints to map the same physical points over time called the trajectory constraints. Under these constraints, we show that the 4D spatial registration can be formulated as a multichannel registration of 3D images. To solve it, we propose a novel version of the Diffeomorphic Demons (DD) algorithm extended to vector-valued 3D images, the Multichannel Diffeomorphic Demons (MDD). For evaluation, this framework is applied to the registration of 4D cardiac computed tomography (CT) sequences and compared to other standard methods with real patient data and synthetic data simulated from a physiologically realistic electromechanical cardiac model. Results show that the trajectory constraints act as a temporal regularization consistent with motion whereas the multichannel registration acts as a spatial regularization. Finally, using these trajectory constraints with multichannel registration yields the best compromise between registration accuracy, temporal and spatial smoothness, and computation times. A prospective example of application is also presented with the spatiotemporal registration of 4D cardiac CT sequences of the same patient before and after radiofrequency ablation (RFA) in case of atrial fibrillation (AF). The intersequence spatial transformations over a cardiac cycle allow to analyze and quantify the regression of left ventricular hypertrophy and its impact on the cardiac function. PMID- 20304733 TI - Statistics of optical coherence tomography data from human retina. AB - Optical coherence tomography (OCT) has recently become one of the primary methods for noninvasive probing of the human retina. The pseudoimage formed by OCT (the so-called B-scan) varies probabilistically across pixels due to complexities in the measurement technique. Hence, sensitive automatic procedures of diagnosis using OCT may exploit statistical analysis of the spatial distribution of reflectance. In this paper, we perform a statistical study of retinal OCT data. We find that the stretched exponential probability density function can model well the distribution of intensities in OCT pseudoimages. Moreover, we show a small, but significant correlation between neighbor pixels when measuring OCT intensities with pixels of about 5 microm. We then develop a simple joint probability model for the OCT data consistent with known retinal features. This model fits well the stretched exponential distribution of intensities and their spatial correlation. In normal retinas, fit parameters of this model are relatively constant along retinal layers, but varies across layers. However, in retinas with diabetic retinopathy, large spikes of parameter modulation interrupt the constancy within layers, exactly where pathologies are visible. We argue that these results give hope for improvement in statistical pathology-detection methods even when the disease is in its early stages. PMID- 20304734 TI - Bayesian k -space-time reconstruction of MR spectroscopic imaging for enhanced resolution. AB - A k-space-time Bayesian statistical reconstruction method (K-Bayes) is proposed for the reconstruction of metabolite images of the brain from proton (1H) magnetic resonance (MR) spectroscopic imaging (MRSI) data. K-Bayes performs full spectral fitting of the data while incorporating structural (anatomical) spatial information through the prior distribution. K-Bayes provides increased spatial resolution over conventional discrete Fourier transform (DFT) based methods by incorporating structural information from higher resolution coregistered and segmented structural MR images. The structural information is incorporated via a Markov random field (MRF) model that allows for differential levels of expected smoothness in metabolite levels within homogeneous tissue regions and across tissue boundaries. By further combining the structural prior model with a k space-time MRSI signal and noise model (for a specific set of metabolites and based on knowledge from prior spectral simulations of metabolite signals), the impact of artifacts generated by low-resolution sampling is also reduced. The posterior-mode estimates are used to define the metabolite map reconstructions, obtained via a generalized expectation-maximization algorithm. K-Bayes was tested using simulated and real MRSI datasets consisting of sets of k-space-time-series (the recorded free induction decays). The results demonstrated that K-Bayes provided qualitative and quantitative improvement over DFT methods. PMID- 20304745 TI - [Human herpesvirus 6]. AB - Human herpesvirus 6 discovered in 1986 is the most ancient human herpesvirus shown by molecular characteristics. Variant B infects children under the age of 2 years by droplets from asymptomatic virus shedding adults occasionally causing exanthema subitum. The virus infects CD4+ macrophages and lymphocytes; subsequently establishes lifelong latency and persistence with occasional shedding through the saliva. This variant frequently reactivates in bone marrow and organ transplant recipients with concomitant immunosuppression causing even fatal complications. It is a cofactor in the pathogenesis of multiple sclerosis, chronic fatigue syndrome, Hodgkin and non-Hodgkin lymphomas. The direct consequences of variant A infection and latency in CD4+ cells are not known. It transactivates HIV infection in vitro and in humans, and facilitates tumor progression induced by human papilloma viruses. Pathogenic effects of both variants are mediated by altered cytokine and chemokine profiles. Serological differentiation of the two variants is unreliable; however, it is possible by using PCR. Ganciclovir, foscarnet and cidofovir can be used for treatment and chemoprophylaxis of severe complications. PMID- 20304746 TI - [Type 1 diabetes mellitus: pathogenesis, symptoms and therapy]. AB - Type 1 diabetes is responsible for approximately 10% of the whole diabetic morbidity. The cause of the disease is an autoimmune process directed against the B-cells leading to progressive and irreversible destruction of these cells, and, consequently, the complete and definitive cessation of endogenous insulin production. Accordingly, these patients should be treated with insulin since the beginning of the disease. The author describes the pathogenesis, epidemiology and symptoms of type 1 diabetes and summarizes the possible ways of therapy and care of type 1 diabetic patients. PMID- 20304747 TI - [The role of autopsies in 21st century medicine]. AB - The decline in the autopsy rates has been already well-known for decades, but the causes of this trend may be not well characterized and not clearly reflected. The causes affect many fields beginning with the graduate courses, the curricular changes, the teaching methods, furthermore the attitudes of clinicians and pathologists toward autopsy, the greater confidence in diagnostic tests, autopsy reporting and regulation. Autopsy will always be the most important teaching performance in medical education and also will be a significant control of clinical practice. Exploring the affected fields (graduate and postgraduate teaching, clinical quality control, health care statistics, money allocation, research), we try to demonstrate the versatility of the autopsies. Improving the status of the autopsies will help the next generation doctors, as well as and the medical system will get better through the evidence-based quality control. The aims of the article are to give a comprehensive exploration of the influenced medical and non-medical factors by post-mortem examination, suggesting, that autopsies will have an important role in the 21st century medicine. PMID- 20304748 TI - [Travel of persons needing medical care; tourist travel of people with chronic kidney insufficiency]. PMID- 20304749 TI - [Treatment of lung cancer]. PMID- 20304751 TI - [Sincere love of human beings and commitment to one's calling--who is the example these days?]. PMID- 20304752 TI - When do first-year college students drink most during the academic year? An internet-based study of daily and weekly drinking. AB - OBJECTIVE: The authors investigated the alcohol consumption trajectories among first-year university students. PARTICIPANTS: A sample of 415 students attending a large university in Southwestern Ontario, Canada, was recruited. METHODS: Students completed a baseline questionnaire and 26 weekly brief Internet surveys assessing alcohol consumption from September 2006 to April 2007. RESULTS: Findings indicated that alcohol consumption varies considerably as a function of time of the academic year. Overall trends indicate that students drink more heavily at the beginning of each semester and less during exam periods. Daily patterns indicate that most drinking occurs on weekends. The highest drinking days in the first academic year included Halloween, New Year's Eve, and St. Patrick's Day. CONCLUSIONS: The present study provides evidence that periods of high and low alcohol consumption are contingent upon specific events and the time of the year. PMID- 20304753 TI - Extreme ritualistic alcohol consumption among college students on game day. AB - Alcohol use and the related consequences associated with college football games are a serious public health issue for university communities. OBJECTIVE: Examining "Extreme Ritualistic Alcohol Consumption" (ERAC), defined as consuming 10 or more drinks on game day for a male, and 8 or more drinks for a female, is the focus of this study. PARTICIPANTS: In the fall of 2006, college students ages 18 to 24 were randomly selected to complete the Game Day Survey. METHODS: Researchers utilized a cross sectional research design to collect data. RESULTS: Sixteen percent of the respondents engaged in ERAC on game day, whereas 36% drank 5 or more drinks (4 or more for females). Male, Caucasian, Greek (members of a social fraternity or sorority), and students of legal drinking age consumed alcohol at disproportionately high rates. CONCLUSION: Alcohol use is common on game day, with a significant percentage of students placing themselves at risk by drinking large amounts of alcohol. PMID- 20304754 TI - Positive changes in perceptions and selections of healthful foods by college students after a short-term point-of-selection intervention at a dining hall. AB - OBJECTIVE: Determine the effects of a short-term, multi-faceted, point-of selection intervention on college students' perceptions and selection of 10 targeted healthful foods in a university dining hall and changes in their self reported overall eating behaviors. PARTICIPANTS: 104 college students, (age 18 23) completed pre-I and post-I surveys. METHODS: Pre-survey collected at dining hall in April 2007, followed by 3-week intervention then post-survey collected via email. Healthy choice indicators, large signs, table tents, flyers and colorful photographs with "benefit-based messages" promoted targeted foods. Response rate to both surveys was 38%. RESULTS: Significantly more participants reported that healthful choices were clearly identified in the dining hall after the intervention. Over 20% of participants reported becoming more aware of healthful food choices in the dining hall after the intervention. Significant increases in self-reported intake were reported for cottage cheese and low-fat salad dressing, with a trend toward increased consumption of fresh fruit. Seven of the 14 assessed eating behaviors had significant changes in the desired direction. Increased awareness of healthful foods was the top reason for self reported changes in overall eating behaviors. CONCLUSION: Short-term, multi faceted, point-of-selection marketing of healthful foods in university dining halls may be beneficial for improving college students' perceptions and selections of targeted healthful foods in the dining hall and may improve overall eating behaviors of college students. PMID- 20304755 TI - Developing mindfulness in college students through movement-based courses: effects on self-regulatory self-efficacy, mood, stress, and sleep quality. AB - OBJECTIVE: This study examined whether mindfulness increased through participation in movement-based courses and whether changes in self-regulatory self-efficacy, mood, and perceived stress mediated the relationship between increased mindfulness and better sleep. PARTICIPANTS: 166 college students enrolled in the 2007-2008 academic year in 15 week classes in Pilates, Taiji quan, or GYROKINESIS. METHODS: At beginning, middle, and end of the semester, participants completed measures of mindfulness, self-regulatory self-efficacy, mood, perceived stress, and sleep quality. RESULTS: Total mindfulness scores and mindfulness subscales increased overall. Greater changes in mindfulness were directly related to better sleep quality at the end of the semester after adjusting for sleep disturbance at the beginning. Tiredness, Negative Arousal, Relaxation, and Perceived Stress mediated the effect of increased mindfulness on improved sleep. CONCLUSIONS: Movement-based courses can increase mindfulness. Increased mindfulness accounts for changes in mood and perceived stress, which explain, in part, improved sleep quality. PMID- 20304756 TI - Comparisons of gambling and alcohol use among college students and noncollege young people in the United States. AB - OBJECTIVE: Gambling and alcohol use were compared for college and noncollege young adults in the US population. PARTICIPANTS: Participants were 1,000 respondents aged 18 to 21. METHODS: Data were analyzed from a representative household sample of US young people aged 14 to 21 years old. Telephone interviews were conducted between August 2005 and January 2007. RESULTS: After taking into account gender, age, race/ethnicity, and socioeconomic status, college student status did not predict gambling, frequent gambling, or problem gambling. In contrast, being a college student was associated with higher levels of alcohol use and problem drinking. Being male was the strongest predictor of both problem gambling and problem drinking. Blacks were less likely than whites to drink heavily; yet they were more likely than whites to gamble heavily. CONCLUSION: Young males should be targeted for prevention and intervention efforts for both problem gambling and problem drinking regardless of college student status. PMID- 20304757 TI - Forcible, drug-facilitated, and incapacitated rape and sexual assault among undergraduate women. AB - OBJECTIVE: To examine the prevalence of drug-related sexual assaults, identify the frequency of assaults that occur following voluntary versus involuntary drug or alcohol consumption, and identify contextual correlates of drug-related assaults. PARTICIPANTS: College-student females (n = 314). METHODS: Volunteers reported experiences with forcible and drug-related sexual assaults in the spring semester of 2004. Follow-up queries regarding the most severe drug-related assaults determined whether the assaults followed voluntary or involuntary alcohol or drug consumption. RESULTS: 29.6% (n = 93) of the respondents reported a drug-related sexual assault or rape; 5.4% (n = 17) reported a forcible sexual assault or rape. Voluntary incapacitation preceded 84.6% of drug-related assaults and involuntary incapacitation preceded 15.4% of drug-related assaults. The majority of drug-related assaults (96.1%) involved alcohol consumption prior to assault. CONCLUSIONS: Drug-related sexual assaults on college campuses are more frequent than are forcible assaults and are most frequently preceded by voluntary alcohol consumption. PMID- 20304759 TI - No fear, just relax and play: social anxiety, alcohol expectancies, and drinking games among college students. AB - OBJECTIVE: The authors examined the association between social anxiety and drinking game (DG) involvement as well as the moderating role of social anxiety relevant alcohol outcome expectancies (AOE) in social anxiety and DG involvement among college students. PARTICIPANTS: Participants were 715 students (74.8% women, Mage = 19.46, SD = 1.22) from 8 US colleges. METHODS: Data were collected via self-report survey from Fall 2005 to Spring 2007. RESULTS: Tension Reduction and Liquid Courage AOE moderated the association between social anxiety and DG participation. Tension Reduction AOE and DG participation were positively related among those with high social anxiety, but were associated negatively for those with low social anxiety. Liquid Courage AOE were associated with increased DG participation for those with low social anxiety, but not for those with high social anxiety. CONCLUSIONS: Findings suggest that social anxiety acts as a protective or a risk factor for DG participation among college students, depending upon AOE. PMID- 20304758 TI - Before the party starts: risk factors and reasons for "pregaming" in college students. AB - OBJECTIVE: "Pregaming"--drinking alcohol prior to going out-is believed to be common, yet empirical examinations are scarce. In this study, we examined who is at risk for pregaming, consequences resulting from it, and motives behind it. PARTICIPANTS: Participants (N = 159, 52% female) were drinkers, aged 18 to 24, recruited from introductory psychology classes. METHODS: In 2005 and 2006, interview measures of drinking and pregaming and self-report demographic, motivational, and reasons for pregaming measures were administered. RESULTS: Two thirds of students pregamed. Younger age, but not Greek affiliation, was associated with heavier pregaming drinking. We found minimal support for the prediction of pregaming by general drinking motives. Specific reasons for pregaming were identified, including saving money and obtaining alcohol when under 21. CONCLUSIONS: Findings highlight the risk associated with pregaming, due to selection effects and to event characteristics. The unique reasons for pregaming must be further understood and addressed in targeted interventions. PMID- 20304760 TI - College women's sexual decision making: cognitive mediation of alcohol expectancy effects. AB - OBJECTIVE: Alcohol has been linked to a variety of risky sexual practices, including inconsistent condom use. Due to the high rates of alcohol consumption among underage college women, greater understanding of the role of alcohol in young women's sexual decision making is warranted. PARTICIPANTS AND METHODS: Female underage (18- to 20-year-old) social drinkers (N = 94) participated in an experiment in which they projected themselves into a written hypothetical sexual situation with a new partner. One half of the situations portrayed alcohol consumption; one half did not involve alcohol consumption. Their appraisals of the situation's sexual potential, impelling and inhibiting cognitions, and sexual behavior intentions were assessed. RESULTS: Results revealed that alcohol's expectancy effects on young women's unprotected sexual intentions were mediated by their cognitive appraisals of the situation. CONCLUSIONS: These findings indicate that alcohol expectancies and their influence on women's sexual decisions should be incorporated into sexual risk reduction efforts. PMID- 20304761 TI - Health literacy in college students. AB - OBJECTIVE: The purpose of this study was to assess the health literacy levels, and the potential importance of healthy literacy, of college students. PARTICIPANTS: Courses were randomly selected from all upper level undergraduate courses at a large Research I university to obtain a sample size of N = 399. METHODS: During the 2007-2008 school year, students were administered the Test of Functional Health Literacy (TOFHLA), which assessed both numeracy and reading comprehension utilizing real-life health care materials. The numeracy scale (n = 17) assessed understanding of prescription labels, appointment slips, and glucose monitoring using actual hospital forms and labels for prescription vials. Ten prompts were given, and participants had to answer quantitatively. The reading comprehension scale (n = 50) assessed understanding of health care texts through 3 reading passages, including instructions for preparation for an upper gastrointestinal (GI) series, Medicaid patient rights and responsibilities, and hospital informed consent agreement. A modified Cloze procedure was employed; every fifth to seventh word in each passage was omitted and the participant selected the best word to fill in the blank from a list of 4 possible choices. RESULTS: The mean health literacy score was 93.83, which was considered adequate functional health literacy. In terms of importance of health literacy to the students, it was found that a majority valued its importance (89.3%). CONCLUSIONS: Indeed this group of university students would seem to have good health literacy levels that would allow them to navigate the health care system. However, many students still had problems with individual TOFHLA items, particularly the numeracy questions. PMID- 20304762 TI - Drinking game participation among undergraduate students attending National Alcohol Screening Day. AB - OBJECTIVES, PARTICIPANTS, METHODS: Drinking game participation has increased in popularity among college students and is associated with increased alcohol consumption and alcohol-related problems. The current study investigated drinking game participation among 133 undergraduates attending National Alcohol Screening Day (NASD) in April of 2007. RESULTS: A large percentage of the sample reported lifetime (77%) and recent (52%) drinking game participation. Males were more likely to report recent participation and reported higher levels of consumption while playing drinking games. Drinking game participants were more likely to experience a range of alcohol-related problems, and the relationship between drinking game participation and alcohol-related problems was mediated by weekly alcohol consumption. CONCLUSIONS: These results suggest that drinking game participation is a risk factor for elevated levels of alcohol consumption and alcohol-related problems. Programs should be developed to educate students about the risks of drinking game participation, and prevention programs like NASD should address drinking games. PMID- 20304763 TI - Glucose prevents the fall in ventromedial hypothalamic GABA that is required for full activation of glucose counterregulatory responses during hypoglycemia. AB - Local delivery of glucose into a critical glucose-sensing region within the brain, the ventromedial hypothalamus (VMH), can suppress glucose counterregulatory responses to systemic hypoglycemia. Here, we investigated whether this suppression was accomplished through changes in GABA output in the VMH. Sprague-Dawley rats had catheters and guide cannulas implanted. Eight to ten days later, microdialysis-microinjection probes were inserted into the VMH, and they were dialyzed with varying concentrations of glucose from 0 to 100 mM. Two groups of rats were microdialyzed with 100 mM glucose and microinjected with either the K(ATP) channel opener diazoxide or a GABA(A) receptor antagonist. These animals were then subjected to a hyperinsulinemic-hypoglycemic glucose clamp. As expected, perfusion of glucose into the VMH suppressed the counterregulatory responses. Extracellular VMH GABA levels positively correlated with the concentration of glucose in the perfusate. In turn, extracellular GABA concentrations in the VMH were inversely related to the degree of counterregulatory hormone release. Of note, microinjection of either diazoxide or the GABA(A) receptor antagonist reversed the suppressive effects of VMH glucose delivery on counterregulatory responses. Some GABAergic neurons in the VMH respond to changes in local glucose concentration. Glucose in the VMH dose dependently stimulates GABA release, and this in turn dose-dependently suppresses the glucagon and epinephrine responses to hypoglycemia. These data suggest that during hypoglycemia a decrease in glucose concentration within the VMH may provide an important signal that rapidly inactivates VMH GABAergic neurons, reducing inhibitory GABAergic tone, which in turn enhances the counterregulatory responses to hypoglycemia. PMID- 20304765 TI - Programming of rat adrenal medulla by neonatal hyperleptinemia: adrenal morphology, catecholamine secretion, and leptin signaling pathway. AB - Leptin serum concentration in early life is an important factor for adequate future development of the offspring. Previously, we demonstrated that hyperleptinemia on lactation programmed for hyperleptinemia, central leptin resistance with lower expression of the long form of leptin receptor at hypothalamus, and higher medullary catecholamine levels with cardiovascular consequences at adulthood. The central objective of this study was to determine the direct effect of leptin on adrenal medullary function of adult rats that were leptin treated during lactation. Adrenal morphology was also accessed. Recombinant murine leptin was injected in the pups during the first 10 days of life (group L, leptin-programmed) or at adulthood during 6 days (group LC). The controls of both experiments received saline (groups C and CC). Both treatments resulted in hyperleptinemia at 150 days old (+78% and 2-fold increase, respectively; P < 0.05). Programmed animals showed hypertrophy of adrenal and higher adrenal catecholamine content at 150 days old (3-fold increase, P < 0.05), and no changes were observed in the LC group. However, LC rats had lower adrenal content of tyrosine hydroxylase (-17%, P < 0.05). Leptin-programmed rats had a lower response to leptin in vitro stimulation (-22%, P < 0.05) and lower expression of key proteins of the leptin signaling pathway, leptin receptor and janus tyrosine kinase 2 in the medullas (-61% and -29%, respectively, P < 0.05). However, they presented higher expression of phosphorylated signal transducer and activator of transcription 3 (+2-fold, P < 0.05). Leptin treatment at adulthood did not affect these parameters. The higher catecholamine synthesis and secretion in the leptin-programmed rats observed in our previous study does not seem to be a consequence of the direct effect of leptin on the medullas. We suggest that the hyperleptinemia of the programmed animals increases adrenal medullary function through sympathetic nervous system activation. In conclusion, high leptin levels on lactation program the activity of the sympathoadrenal system at adulthood that may contribute to the development of adult chronic diseases such as hypertension. PMID- 20304764 TI - An increase in essential amino acid availability upregulates amino acid transporter expression in human skeletal muscle. AB - Essential amino acids (EAA) stimulate skeletal muscle mammalian target of rapamycin complex 1 (mTORC1) signaling and protein synthesis. It has recently been reported that an increase in amino acid (AA) transporter expression during anabolic conditions is rapamycin-sensitive. The purpose of this study was to determine whether an increase in EAA availability increases AA transporter expression in human skeletal muscle. Muscle biopsies were obtained from the vastus lateralis of seven young adult subjects (3 male, 4 female) before and 1-3 h after EAA ingestion (10 g). Blood and muscle samples were analyzed for leucine kinetics using stable isotopic techniques. Quantitative RT-PCR, and immunoblotting were used to determine the mRNA and protein expression, respectively, of AA transporters and members of the general AA control pathway [general control nonrepressed (GCN2), activating transcription factor (ATF4), and eukaryotic initiation factor (eIF2) alpha-subunit (Ser(52))]. EAA ingestion increased blood leucine concentration, delivery of leucine to muscle, transport of leucine from blood into muscle, intracellular muscle leucine concentration, ribosomal protein S6 (Ser(240/244)) phosphorylation, and muscle protein synthesis. This was followed with increased L-type AA transporter (LAT1), CD98, sodium-coupled neutral AA transporter (SNAT2), and proton-coupled amino acid transporter (PAT1) mRNA expression at 1 h (P < 0.05) and modest increases in LAT1 protein expression (3 h post-EAA) and SNAT2 protein expression (2 and 3 h post EAA, P < 0.05). Although there were no changes in GCN2 expression and eIF2 alpha phosphorylation, ATF4 protein expression reached significance by 2 h post-EAA (P < 0.05). We conclude that an increase in EAA availability upregulates human skeletal muscle AA transporter expression, perhaps in an mTORC1-dependent manner, which may be an adaptive response necessary for improved AA intracellular delivery. PMID- 20304766 TI - Photon energy dependence of three fortuitous dosemeters from personal electronic devices, measured by optically stimulated luminescence. AB - New data are presented with regard to the relative OSL sensitivity of three different emergency dosemeters irradiated to various photon energies approximately between 48 and 1250 keV using blue excitation light. Investigated components extracted from commonly worn objects include those from USB flash drives (alumina substrate), mobile phones (Ba-rich silicate) and credit cards (chip card module). Several basic properties have been investigated such as the overall radiation sensitivity, the shape of the decay curve and fading of the OSL signal. An increase of the sensitivity for low energies relative to (60)Co gamma rays can be observed for the three dosemeters, the increase being very pronounced for the Ba-rich component (factor of 10) and less pronounced for the chip card module (factor of 2). It is concluded that proper dose correction factors for photon energy have to be applied in order to accurately determine the absorbed dose to tissue. The OSL sensitivity to neutron irradiation was investigated as well, but this was found to be less than the gamma sensitivity. PMID- 20304767 TI - The future of medical imaging. AB - The organisers of this conference have kindly provided me with the forum to look forward and examine the future of medical imaging. My view of the future is informed by my own research directions; thus, I illustrate my vision of the future with results from my own research, and from the research that has motivated me over the last few years. As such, the results presented are specific to the field of breast imaging; however, I believe that the trends presented have general applicability, and hope that this discourse will motivate new research. My vision of the future can be summarised in accordance with three broad trends: (1) increased prevalence of low-dose tomographic X-ray imaging; (2) continuing advances in functional and molecular X-ray imaging; and (3) novel image-based biomarker discovery. PMID- 20304768 TI - Natural radioactivity in roadside soil along Jamshedpur-Musabani road: a mineralised and mining region, Jharkhand and associated risk. AB - The specific activity and the gamma radiation dose rates due to naturally occurring radioactive materials ((238)U, (232)Th and (40)K) were determined in 26 roadside surface soils along Jamshedpur-Musabani road-a mineralised and mining region, using high-resolution gamma-ray spectrometry. The concentrations of (238)U, (232)Th and (40)K in the soil samples were found to be in the range of 16.6 +/- 0.6-390.5 +/- 1.6, 24.1 +/- 0.7-148.2 +/- 2.1 and 85.9 +/- 3.8-881.6 +/- 22.4 Bq kg(-1), respectively. The annual effective dose equivalent was found to be in the range of 0.04-0.32 mSv y(-1) with an average value of 0.13 mSv y(-1). The excess cancer risk is in the range of 0.16 x 10(-3)-1.22 x 10(-3) with an average value of 0.49 x 10(-3). PMID- 20304769 TI - Application of a statistical software package for analysis of large patient dose data sets obtained from RIS. AB - For the purpose of patient dose audit, clinical audit and radiology workload analysis, data from Radiology Information Systems (RIS) at many hospitals are collected using a database and the analysis was automated using a statistical package and Visual Basic coding. The database is a Structured Query Language database, which can be queried using an off-the-shelf statistical package, Statistica. Macros were created to automatically format the data to a consistent format between different hospitals ready for analysis. These macros can also be used to automate further analysis such as detailing mean kV, mAs and entrance surface dose per room and per gender. Standard deviation and standard error of the mean are also generated. Graphs can also be generated to illustrate the trends in doses between different variables such as room and gender. Collectively, this information can be used to generate a report. A process that once could take up to 1 d to complete now takes around 1 h. A major benefit in providing the service to hospital trusts is that less resource is now required to report on RIS data, making the possibility of continuous dose audit more likely. Time that was spent on sorting through data can now be spent on improving the analysis to provide benefit to the customer. Using data sets from RIS is a good way to perform dose audits as the huge numbers of data available provide the bases for very accurate analysis. Using macros written in Statistica Visual Basic has helped sort and consistently analyse these data. Being able to analyse by exposure factors has provided a more detailed report to the customer. PMID- 20304770 TI - Metformin supplementation and life span in Fischer-344 rats. AB - Calorie restriction (CR) has been known for more than 70 years to extend life span and delay disease in rodent models. Metformin administration in rodent disease models has been shown to delay cancer incidence and progression, reduce cardiovascular disease and extend life span. To more directly test the potential of metformin supplementation (300 mg/kg/day) as a CR mimetic, life-span studies were performed in Fischer-344 rats and compared with ad libitum feeding and CR (30%). The CR group had significantly reduced food intake and body weight throughout the study. Body weight was significantly reduced in the metformin group compared with control during the middle of the study, despite similar weekly food intake. Although CR significantly extended early life span (25th quantile), metformin supplementation did not significantly increase life span at any quantile (25th, 50th, 75th, or 90th), overall or maximum life span (p > .05) compared with control. PMID- 20304772 TI - Trajectories of adherence to airway clearance therapy for patients with cystic fibrosis. AB - OBJECTIVE: Although cross-sectional studies have demonstrated poor adherence to airway clearance therapy (ACT) for patients with cystic fibrosis (CF), no studies have identified longitudinal patterns of adherence. The objective was to characterize and identify predictors of ACT adherence trajectories for individuals with CF. METHODS: Secondary data analyses were conducted for a randomized clinical trial examining differences in three ACTs. Participants (n = 153; M = 14.3 years, 55% male, 86% Caucasian, baseline FEV(1)% predicted: M = 86.7)/primary caregivers completed Daily Phone Diaries, an empirically supported adherence measure, every 4 months. RESULTS: Group-based trajectory modeling revealed the best-fitting solution was a three-group model: low-adherence (14%), medium-adherence (49%), and high-adherence (37%) groups. ACT type was the only significant predictor of adherence trajectories. DISCUSSION: Three trajectories of adherence to ACT for patients with CF were found. With the identification of trajectories, adherence interventions can be targeted for the subgroup at highest risk in order to prevent poor health outcomes. PMID- 20304771 TI - A meta-analysis of four genome-wide association studies of survival to age 90 years or older: the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium. AB - BACKGROUND: Genome-wide association studies (GWAS) may yield insights into longevity. METHODS: We performed a meta-analysis of GWAS in Caucasians from four prospective cohort studies: the Age, Gene/Environment Susceptibility-Reykjavik Study, the Cardiovascular Health Study, the Framingham Heart Study, and the Rotterdam Study participating in the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium. Longevity was defined as survival to age 90 years or older (n = 1,836); the comparison group comprised cohort members who died between the ages of 55 and 80 years (n = 1,955). In a second discovery stage, additional genotyping was conducted in the Leiden Longevity Study cohort and the Danish 1905 cohort. RESULTS: There were 273 single-nucleotide polymorphism (SNP) associations with p < .0001, but none reached the prespecified significance level of 5 x 10(-8). Of the most significant SNPs, 24 were independent signals, and 16 of these SNPs were successfully genotyped in the second discovery stage, with one association for rs9664222, reaching 6.77 x 10( 7) for the combined meta-analysis of CHARGE and the stage 2 cohorts. The SNP lies in a region near MINPP1 (chromosome 10), a well-conserved gene involved in regulation of cellular proliferation. The minor allele was associated with lower odds of survival past age 90 (odds ratio = 0.82). Associations of interest in a homologue of the longevity assurance gene (LASS3) and PAPPA2 were not strengthened in the second stage. CONCLUSION: Survival studies of larger size or more extreme or specific phenotypes may support or refine these initial findings. PMID- 20304776 TI - The glycocalyx of human, bovine and murine microvascular endothelial cells cultured in vitro. AB - This study investigated the morphology and thickness of the glycocalyx linings of microvascular endothelial cells (MVEC). Three distinct cell types were used: the human dermal cells (HDMVEC), the murine cardiac cells (MCMVEC) and the bovine luteal cells (BLMVEC). Cells were cultivated for 48 h. Glycocalyx was stained with ruthenium red and examined under a transmission electron microscope. The glycocalyx of HDMVEC was thin and constant (10-22 nm). No glycocalyx was detected within intracellular vesicles. Two cell populations of MCMVEC were recorded. The minor MCMVEC population was well differentiated and covered with heterogenous glycocalyx (2-200 nm). Conglomerates formed above the baseline along the cell extensions. The major MCMVEC population was undifferentiated and coated by a smooth and thin (12-25 nm) layer of glycocalyx. Intracellular vesicles were also coated with glycocalyx. In the BLMVEC population, 10% had 3-170 nm of discontinuous glycocalyx. Rough conglomerates were observed along cell sprouts. Their intracellular vesicles were coated with glycocalyx. The study found vast differences in the morphology and thickness of endothelial glycocalyx among different MVEC under in vitro cultivation. The only record of active endocytosis was in BLMVEC and MCMVEC. No evidence of active endocytosis was found in HDMVEC. PMID- 20304778 TI - Phase II study of combination chemotherapy with biweekly cetuximab and irinotecan for pre-treated metastatic colorectal cancer harboring wild-type KRAS. AB - Standard weekly cetuximab and irinotecan is an effective regimen in heavily pre treated patients with metastatic colorectal cancer. The aim of this study is to prospectively evaluate the efficacy of combination chemotherapy with biweekly cetuximab and irinotecan in patients with pre-treated metastatic colorectal cancer harboring wild-type KRAS. A total of 30 patients will be enrolled at four medical institutions. The primary endpoint is response rate. The secondary endpoints include adverse events, progression-free survival and overall survival. The pharmacokinetics of cetuximab will also be evaluated in five patients. PMID- 20304777 TI - The AZFc region of the Y chromosome: at the crossroads between genetic diversity and male infertility. AB - BACKGROUND: The three azoospermia factor (AZF) regions of the Y chromosome represent genomic niches for spermatogenesis genes. Yet, the most distal region, AZFc, is a major generator of large-scale variation in the human genome. Determining to what extent this variability affects spermatogenesis is a highly contentious topic in human reproduction. METHODS: In this review, an extensive characterization of the molecular mechanisms responsible for AZFc genotypical variation is undertaken. Such data are complemented with the assessment of the clinical consequences for male fertility imputable to the different AZFc variants. For this, a critical re-evaluation of 23 association studies was performed in order to extract unifying conclusions by curtailing methodological heterogeneities. RESULTS: Intrachromosomal homologous recombination mechanisms, either crossover or non-crossover based, are the main drivers for AZFc genetic diversity. In particular, rearrangements affecting gene dosage are the most likely to introduce phenotypical disruptions in the spermatogenic profile. In the specific cases of partial AZFc deletions, both the actual existence and the severity of the spermatogenic defect are dependent on the evolutionary background of the Y chromosome. CONCLUSIONS: AZFc is one of the most genetically dynamic regions in the human genome. This property may serve as counter against the genetic degeneracy associated with the lack of a meiotic partner. However, such strategy comes at a price: some rearrangements represent a risk factor or a de facto causative agent of spermatogenic disruption. Interestingly, this precarious balance is modulated, among other yet unknown factors, by the evolutionary history of the Y chromosome. PMID- 20304779 TI - Over-expression of neuroepithelial-transforming protein 1 confers poor prognosis of patients with gliomas. AB - OBJECTIVE: Neuroepithelial-transforming protein 1 is a member of the guanine nucleotide exchange factor family, a group of proteins which are known to activate and thereby regulate Rho family members. Deregulation of neuroepithelial transforming protein 1 expression has been found in certain types of human tumors. To investigate its prognostic value in human gliomas, which is currently unknown, we examined the correlation between neuroepithelial-transforming protein 1 expression and prognosis in patients with gliomas. METHODS: Immunohistochemical staining was performed to detect neuroepithelial-transforming protein 1 expression patterns in the biopsies from 96 patients with primary gliomas. Kaplan Meier survival and Cox's regression analyses were performed to evaluate the prognosis of patients. RESULTS: Immunohistochemical analysis with anti neuroepithelial-transforming protein 1 antibody revealed that neuroepithelial transforming protein 1 was significantly associated with the Karnofsky performance scale score and World Health Organization grades of patients with gliomas. Especially, the positive expression rates of neuroepithelial transforming protein 1 were significantly higher in patients with higher grade (P = 0.001) and lower Karnofsky's performance scale score (P = 0.005). The median survival of patients with high neuroepithelial-transforming protein 1 expression was significantly shorter than that with low expression and without expression (316, 892 and 1180 days, respectively). Cox's multifactor analysis showed that the Karnofsky performance scale (P = 0.01), World Health Organization grade (P = 0.008) and neuroepithelial-transforming protein 1 (P = 0.006) were independent prognosis factors for human glioma. CONCLUSIONS: Taken together, our study indicates for the first time that neuroepithelial-transforming protein 1 status may be a highly sensitive marker for glioma prognosis and suggest that the expression patterns of neuroepithelial-transforming protein 1 might be a potent tool for predicting the clinical prognosis of glioma patients. PMID- 20304781 TI - Ectomycorrhizal identity determines respiration and concentrations of nitrogen and non-structural carbohydrates in root tips: a test using Pinus sylvestris and Quercus robur saplings. AB - Fine roots play a significant role in plant and ecosystem respiration (RS); therefore, understanding factors controlling that process is important both to advancing understanding and potentially in modelling carbon (C) budgets. However, very little is known about the extent to which ectomycorrhizal (ECM) identity may influence RS or the underlying chemistry that may determine those rates. In order to test these relationships, we examined RS, measured as O(2) consumption, of first-order ECM root tips of Pinus sylvestris L. and Quercus robur L. saplings in relation to their ECM fungal symbionts and associated nitrogen (N), C and non structural carbohydrate concentrations. Roots of P. sylvestris were colonized by Rhizopogon roseolus, Tuber sp. 1 and an unknown species of Pezizales. Fungal species colonizing Q. robur roots were Hebeloma sp., Tuber sp. 2 and one unidentified ECM fungus described as Tuber-like based on ECM morphology. ECM RS rates for different host species were significantly different and more than 97% of the variation in RS within a host species was explained by ECM root tip N concentrations. This may indicate that some of the variability in fine root RS-N relationships observed between and within different host species or their functional groups may be related to intraspecific host species differences in root tip N concentration among ECM fungal associates. PMID- 20304782 TI - Proteomics-based study on asthenozoospermia: differential expression of proteasome alpha complex. AB - With a view to understand the molecular basis of sperm motility, we have tried to establish the human sperm proteome by two-dimensional PAGE MALDI MS/MS analysis. We report identification of 75 different proteins in the human spermatozoa. Comparative proteome analysis was carried out for asthenozoospermic and normozoospermic patients to understand the molecular basis of sperm motility. Analysis revealed eight proteins (including one unidentified) with altered intensity between the groups. Differential proteins distributed into three functional groups: 'energy and metabolism' (triose-phosphate isomerase, glycerol kinase 2, testis specific isoform and succinyl-CoA:3-ketoacid co-enzyme A transferase 1, mitochondrial precursor); 'movement and organization' (tubulin beta 2C and tektin 1) and 'protein turnover, folding and stress response' (proteasome alpha 3 subunit and heat shock-related 70 kDa protein 2). It was interesting to note that although the proteins falling in the functional group of 'energy and metabolism' are higher in the asthenozoospermic patients, the other two functional groups contain proteins, which are higher in the normozoospermic samples. Validation of results carried out for proteasome alpha 3 subunit by immunoblotting and confocal microscopy, confirmed significant changes in intensity of proteasome alpha 3 subunit in asthenozoospermic samples when compared with normozoospermic controls. Significant positive correlation too was found between proteasome alpha 3 subunit levels and rapid, linear progressive motility of the spermatozoa. In our understanding, this data would contribute appreciably to the presently limited information available about the proteins implicated in human sperm motility. PMID- 20304780 TI - Parkinson disease protein DJ-1 converts from a zymogen to a protease by carboxyl terminal cleavage. AB - Mutations in DJ-1 cause recessively transmitted early-onset Parkinson disease (PD), and oxidative damage to DJ-1 has been associated with the pathogenesis of late-onset sporadic PD. The precise biochemical function of DJ-1 remains elusive. Here, we report that DJ-1 is synthesized as a latent protease zymogen with low intrinsic proteolytic activity. DJ-1 protease zymogen is activated by the removal of a 15-amino acid peptide at its C terminus. The activated DJ-1 functions as a cysteine protease with Cys-106 and His-126 as the catalytic diad. We show that endogenous DJ-1 in dopaminergic cells undergoes C-terminal cleavage in response to mild oxidative stress, suggesting that DJ-1 protease activation occurs in a redox-dependent manner. Moreover, we find that the C-terminally cleaved form of DJ-1 with activated protease function exhibits enhanced cytoprotective action against oxidative stress-induced apoptosis. The cytoprotective action of DJ-1 is abolished by the C106A and H126A mutations. Our findings support a role for DJ-1 protease in cellular defense against oxidative stress and have important implications for understanding and treating PD. PMID- 20304783 TI - Neonatal outcome associated with singleton birth at 34-41 weeks of gestation. AB - BACKGROUND: Approximately 75% of preterm births are late-preterm (34(0/7) to 36(6/7) weeks gestation). This group has usually been considered as a whole in studies assessing the outcome of these preterm infants by comparison with term infants. However, the respective contribution to prognosis of each week of gestation has not been fully clarified. METHODS: A population-based study of 150 426 live-born singleton neonates with gestational ages ranging from 34 to 41 weeks of gestation. RESULTS: The rate of severe respiratory disorders (treated by mechanical ventilation and/or nasal continuous positive airway pressure) markedly declined with gestational age from 19.8% at 34 weeks to 0.28% at 39-41 weeks. Between 34 and 38 weeks, each additional week diminished the relative risk (crude or adjusted) of severe respiratory disorders by a factor varying from 2 to 3. The rate of poor prognosis (death and/or severe neurological condition) significantly declined between 34 and 38 weeks and remained stable thereafter. A multivariate analysis showed that antepartum haemorrhage and hypertensive disorders during pregnancy were significantly associated with severe respiratory disorders and poor outcome. Diabetes was an additional factor associated with severe respiratory disorders. CONCLUSIONS: Future studies should delineate more precisely the respective contribution of gestational age, maternal complication and induced delivery in the prognosis of infants born between 33 and 39 weeks gestation. PMID- 20304784 TI - Right ventricular involvement in anterior myocardial infarction: a translational approach. AB - AIMS: The aim of the present study was to evaluate the involvement of the right ventricle (RV) in reperfused anterior ST-elevation myocardial infarction (STEMI). METHODS AND RESULTS: Left anterior descending (LAD)-perfused area (using thioflavin-S staining after selective infusion in proximal LAD artery, %), infarct size (using triphenyltetrazolium chloride staining, %), and salvaged myocardium (% of LAD-perfused area) in the right and left ventricle (LV) were quantified in a 90-min LAD occlusion 3-day reperfusion model in swine (n = 8). Additionally, we studied, using cardiovascular magnetic resonance, 20 patients with a first STEMI due to proximal LAD occlusion treated with primary angioplasty. Area at risk (T2-weighted sequence, %), infarct size (late enhancement imaging, %), and salvaged myocardium (% of area at risk) in the right and LV were quantified. In swine, a large LAD-perfused area was detected both in the right and LV (30 +/- 5 vs. 62 +/- 15%, P< 0.001) but more salvaged myocardium (94 +/- 6 vs. 73 +/- 11%, P< 0.001) resulted in a smaller right ventricular infarct size (2 +/- 1 vs. 16 +/- 5%, P< 0.001). Similarly, in patients a large area at risk was detected both in the right and LV (34 +/- 13 vs. 43 +/- 12%, P = 0.02). More salvaged myocardium (94 +/- 10 vs. 33 +/- 26%, P < 0.001) resulted in a smaller infarct size (2 +/- 3 vs. 30 +/- 16%, P< 0.001) in the RV. CONCLUSION: In reperfused extensive anterior STEMI, a large area of the RV is at risk but the resultant infarct size is small. PMID- 20304785 TI - Severe dyslipidaemia, atherosclerosis, and sudden cardiac death in mice lacking all NO synthases fed a high-fat diet. AB - AIMS: The precise role of the nitric oxide synthase (NOS) system in lipid metabolism remains to be elucidated. We addressed this point in mice that we have recently developed and that lack all three NOS isoforms. METHODS AND RESULTS: Wild-type (WT), singly, doubly, and triply NOS(-/-) mice were fed either a regular or high-cholesterol diet for 3-5 months. The high-cholesterol diet significantly increased serum low-density lipoprotein (LDL) cholesterol levels in all the genotypes when compared with the regular diet. Importantly, when compared with the WT genotype, the serum LDL cholesterol levels in the high-cholesterol diet were significantly and markedly elevated only in the triply NOS(-/-) genotype, but not in any singly or doubly NOS(-/-) genotypes, and this was associated with remarkable atherosclerosis and sudden cardiac death, which occurred mainly in the 4-5 months after the high-cholesterol diet. Finally, hepatic LDL receptor expression was markedly reduced only in the triply NOS(-/-) genotype, accounting for the diet-induced dyslipidaemia in the genotype. CONCLUSION: These results provide the first direct evidence that complete disruption of all NOS genes causes severe dyslipidaemia, atherosclerosis, and sudden cardiac death in response to a high-fat diet in mice in vivo through the down-regulation of the hepatic LDL receptor, demonstrating the critical role of the whole endogenous NOS system in maintaining lipid homeostasis. PMID- 20304786 TI - Atlas of rice grain filling-related metabolism under high temperature: joint analysis of metabolome and transcriptome demonstrated inhibition of starch accumulation and induction of amino acid accumulation. AB - High temperature impairs grain filling by inhibiting the deposition of storage materials such as starch and protein. To comprehend its impact on grain filling metabolism in rice (Oryza sativa), levels of metabolites and transcripts related to central pathways of metabolism were simultaneously determined in developing caryopses exposed to high temperature (33 degrees C/28 degrees C) and a control temperature (25 degrees C/20 degrees C) during the milky stage. A capillary electrophoresis-based metabolomic analysis revealed that high temperature increased the accumulation of sucrose and pyruvate/ oxaloacetate-derived amino acids and decreased levels of sugar phosphates and organic acids involved in glycolysis/gluconeogenesis and the tricarboxylic acid (TCA) cycle, respectively. A transcriptomic analysis using a whole genome-covering microarray unraveled the possible metabolic steps causing the shortage of storage materials under the elevated temperature. Starch deposition might be impaired by down-regulation of sucrose import/degradation and starch biosynthesis, and/or up-regulation of starch degradation as well as inefficient ATP production by an inhibited cytochrome respiration chain, as indicated by the response of gene expression to high temperature. Amino acid accumulation might be attributed to the heat-stable import of amino acids into the caryopsis and/or repression of protein synthesis especially the tRNA charging step under high temperature. An atlas showing the effect of high temperature on levels of metabolites and gene expression in the central metabolic pathways is presented. PMID- 20304787 TI - Effects of AOX1a deficiency on plant growth, gene expression of respiratory components and metabolic profile under low-nitrogen stress in Arabidopsis thaliana. AB - Expression of alternative oxidase (AOX) and cyanide (CN)-resistant respiration are often highly enhanced in plants exposed to low-nitrogen (N) stress. Here, we examined the effects of AOX deficiency on plant growth, gene expression of respiratory components and metabolic profiles under low-N stress, using an aox1a knockout transgenic line (aox1a) of Arabidopsis thaliana. We exposed wild-type (WT) and aox1a plants to low-N stress for 7 d and analyzed their shoots and roots. In WT plants, the AOX1a mRNA levels and AOX capacity increased in proportion to low-N stress. Expression of the genes of the components for non phosphorylating pathways and antioxidant enzymes was enhanced, but differences between WT and aox1a plants were small. Metabolome analyses revealed that AOX deficiency altered the levels of certain metabolites, such as sugars and sugar phosphates, in the shoots under low-N stress. However, the carbon (C)/N ratios and carbohydrate levels in aox1a plants were similar to those in the WT under low N stress. Our results indicated that the N-limited stress induced AOX expression in A. thaliana plants, but the induced AOX may not play essential roles under stress due to low-N alone, and the C/N balance under low-N stress may be tightly regulated by systems other than AOX. PMID- 20304788 TI - Are articulatory commands automatically and involuntarily activated during speech perception? PMID- 20304790 TI - An uncorrelated relaxed-clock analysis suggests an earlier origin for flowering plants. AB - We present molecular dating analyses for land plants that incorporate 33 fossil calibrations, permit rates of molecular evolution to be uncorrelated across the tree, and take into account uncertainties in phylogenetic relationships and the fossil record. We attached a prior probability to each fossil-based minimum age, and explored the effects of relying on the first appearance of tricolpate pollen grains as a lower bound for the age of eudicots. Many of our divergence-time estimates for major clades coincide well with both the known fossil record and with previous estimates. However, our estimates for the origin of crown-clade angiosperms, which center on the Late Triassic, are considerably older than the unequivocal fossil record of flowering plants or than the molecular dates presented in recent studies. Nevertheless, we argue that our older estimates should be taken into account in studying the causes and consequences of the angiosperm radiation in relation to other major events, including the diversification of holometabolous insects. Although the methods used here do help to correct for lineage-specific heterogeneity in rates of molecular evolution (associated, for example, with evolutionary shifts in life history), we remain concerned that some such effects (e.g., the early radiation of herbaceous clades within angiosperms) may still be biasing our inferences. PMID- 20304791 TI - Keeping sphingolipid levels nORMal. PMID- 20304792 TI - Temporal dynamics of spontaneous MEG activity in brain networks. AB - Functional MRI (fMRI) studies have shown that low-frequency (<0.1 Hz) spontaneous fluctuations of the blood oxygenation level dependent (BOLD) signal during restful wakefulness are coherent within distributed large-scale cortical and subcortical networks (resting state networks, RSNs). The neuronal mechanisms underlying RSNs remain poorly understood. Here, we describe magnetoencephalographic correspondents of two well-characterized RSNs: the dorsal attention and the default mode networks. Seed-based correlation mapping was performed using time-dependent MEG power reconstructed at each voxel within the brain. The topography of RSNs computed on the basis of extended (5 min) epochs was similar to that observed with fMRI but confined to the same hemisphere as the seed region. Analyses taking into account the nonstationarity of MEG activity showed transient formation of more complete RSNs, including nodes in the contralateral hemisphere. Spectral analysis indicated that RSNs manifest in MEG as synchronous modulation of band-limited power primarily within the theta, alpha, and beta bands-that is, in frequencies slower than those associated with the local electrophysiological correlates of event-related BOLD responses. PMID- 20304794 TI - Functional delivery of viral miRNAs via exosomes. AB - Noncoding regulatory microRNAs (miRNAs) of cellular and viral origin control gene expression by repressing the translation of mRNAs into protein. Interestingly, miRNAs are secreted actively through small vesicles called "exosomes" that protect them from degradation by RNases, suggesting that these miRNAs may function outside the cell in which they were produced. Here we demonstrate that miRNAs secreted by EBV-infected cells are transferred to and act in uninfected recipient cells. Using a quantitative RT-PCR approach, we demonstrate that mature EBV-encoded miRNAs are secreted by EBV-infected B cells through exosomes. These EBV-miRNAs are functional because internalization of exosomes by MoDC results in a dose-dependent, miRNA-mediated repression of confirmed EBV target genes, including CXCL11/ITAC, an immunoregulatory gene down-regulated in primary EBV associated lymphomas. We demonstrate that throughout coculture of EBV-infected B cells EBV-miRNAs accumulate in noninfected neighboring MoDC and show that this accumulation is mediated by transfer of exosomes. Thus, the exogenous EBV-miRNAs transferred through exosomes are delivered to subcellular sites of gene repression in recipient cells. Finally, we show in peripheral blood mononuclear cells from patients with increased EBV load that, although EBV DNA is restricted to the circulating B-cell population, EBV BART miRNAs are present in both B-cell and non-B-cell fractions, suggestive of miRNA transfer. Taken together our findings are consistent with miRNA-mediated gene silencing as a potential mechanism of intercellular communication between cells of the immune system that may be exploited by the persistent human gamma-herpesvirus EBV. PMID- 20304793 TI - Functionally distinct hematopoietic stem cells modulate hematopoietic lineage potential during aging by a mechanism of clonal expansion. AB - Aging of the hematopoietic stem cell compartment is believed to contribute to the onset of a variety of age-dependent blood cell pathophysiologies. Mechanistic drivers of hematopoietic stem cell (HSC) aging include DNA damage accumulation and induction of tumor suppressor pathways that combine to reduce the regenerative capacity of aged HSCs. Such mechanisms do not however account for the change in lymphoid and myeloid lineage potential characteristic of HSC aging, which is believed to be central to the decline of immune competence and predisposition to myelogenous diseases in the elderly. Here we have prospectively isolated functionally distinct HSC clonal subtypes, based on cell surface phenotype, bearing intrinsically different capacities to differentiate toward lymphoid and myeloid effector cells mediated by quantitative differences in lineage priming. Finally, we present data supporting a model in which clonal expansion of a class of intrinsically myeloid-biased HSCs with robust self renewal potential is a central component of hematopoietic aging. PMID- 20304796 TI - Guest-free monolayer clathrate and its coexistence with two-dimensional high density ice. AB - Three-dimensional (3D) gas clathrates are ice-like but distinguished from bulk ices by containing polyhedral nano-cages to accommodate small gas molecules. Without space filling by gas molecules, standalone 3D clathrates have not been observed to form in the laboratory, and they appear to be unstable except at negative pressure. Thus far, experimental evidence for guest-free clathrates has only been found in germanium and silicon, although guest-free hydrate clathrates have been found, in recent simulations, able to grow from cold stretched water, if first nucleated. Herein, we report simulation evidence of spontaneous formation of monolayer clathrate ice, with or without gas molecules, within hydrophobic nano-slit at low temperatures. The guest-free monolayer clathrate ice is a low-density ice (LDI) whose geometric pattern is identical to Archimedean 4.8(2)-truncated square tiling, i.e. a mosaic of tetragons and octagons. At large positive pressure, a second phase of 2D monolayer ice, i.e. the puckered square high-density ice (HDI) can form. The triple point of the LDI/liquid/HDI three phase coexistence resembles that of the ice-I(h)/water/ice-III three-phase coexistence. More interestingly, when the LDI is under a strong compression at 200 K, it transforms into the HDI via a liquid intermediate state, the first direct evidence of Ostwald's rule of stages at 2D. The tensile limit of the 2D LDI and water are close to that of bulk ice-I(h) and laboratory water. PMID- 20304797 TI - Raman microscopy and x-ray fluorescence analysis of pigments on medieval and Renaissance Italian manuscript cuttings. AB - Italian medieval and Renaissance manuscript cuttings and miniatures from the Victoria and Albert Museum were analyzed by Raman microscopy to compile a database of pigments used in different periods and different Italian regions. The palette identified in most manuscripts and cuttings was found to include lead white, gypsum, azurite, lazurite, indigo, malachite, vermilion, red lead, lead tin yellow (I), goethite, carbon, and iron gall ink. A few of the miniatures, such as the historiated capital "M" painted by Gerolamo da Cremona and the Petrarca manuscript by Bartolomeo Sanvito, are of exceptional quality and were analyzed extensively; some contained unusual materials. The widespread usage of iron oxides such as goethite and hematite as minor components of mixtures with azurite is particularly notable. The use of a needle-shaped form of iron gall ink as a pigment rather than a writing material was established by both Raman microscopy and x-ray fluorescence spectroscopy for the Madonna and Child by Franco de' Russi. PMID- 20304795 TI - Amyloid-like interactions within nucleoporin FG hydrogels. AB - The 62 kDa FG repeat domain of the nucleoporin Nsp1p forms a hydrogel-based, sieve-like permeability barrier that excludes inert macromolecules but allows rapid entry of nuclear transport receptors (NTRs). We found that the N-terminal part of this domain, which is characterized by Asn-rich inter-FG spacers, forms a tough hydrogel. The C-terminal part comprises charged inter-FG spacers, shows low gelation propensity on its own, but binds the N-terminal part and passivates the FG hydrogel against nonselective interactions. It was previously shown that a hydrophobic collapse involving Phe residues is required for FG hydrogel formation. Using solid-state NMR spectroscopy, we now identified two additional types of intragel interactions, namely, transient hydrophobic interactions between Phe and methyl side chains as well as intermolecular beta-sheets between the Asn-rich spacer regions. The latter appear to be the kinetically most stable structures within the FG hydrogel. They are also a central feature of neuronal inclusions formed by Asn/Gln-rich amyloid and prion proteins. The cohesive properties of FG repeats and the Asn/Gln-rich domain from the yeast prion Sup35p appear indeed so similar to each other that these two modules interact in trans. Our data, therefore, suggest a fully unexpected cellular function of such interchain beta-structures in maintaining the permeability barrier of nuclear pores. They provide an explanation for how contacts between FG repeats might gain the kinetic stability to suppress passive fluxes through nuclear pores and yet allow rapid NTR passage. PMID- 20304798 TI - Specific estrogen sulfotransferase (SULT1E1) substrates and molecular imaging probe candidates. AB - This work focuses on the development of specific substrates for estrogen sulfotransferase (SULT1E1) to produce molecular imaging probes for this enzyme. SULT1E1 is a key enzyme in estrogen homeostasis, playing a central role in the prevention and development of human disease. In vitro sulfation assays showed alkyl and aryl substitutions to a fused heterocyclic system modeled after beta naphthol (betaN), based on compounds that interact with the estrogen receptor, rendered several molecules with enhanced specificity for SULT1E1 over SULT1A1*1, SULT1A1*2, SULT1A3, and SULT2A1. Several 6-hydroxy-2-arylbenzothiazoles tested demonstrated excellent affinity--V(max)/K(m) ratios-and specificity for SULT1E1. K(m) values ranged from 0.12-2.36 microM. A strong correlation was observed between polarity of the 4'-sustituent on the 2-aryl moiety (Hammett sigma(p)) and the log(V(max)/K(m)) (r = 0.964). Substrate sensitivity is influenced by the acidity of the 6-phenolic group demonstrated by correlating its (1)H NMR chemical shift (delta(OH)) with the log(V(max)/K(m)) (r = 0.963). Acidity is mediated by the electron withdrawing capacity of the 4'-substituent outlined by the correlation of the C-2 (13)C NMR chemical shift (delta(C2)) with the log(V(max)/K(m)) (r = 0.987). 2-[4-(Methylamino)phenyl]-6-hydroxybenzothiazole (2b) was radiolabeled with carbon-11 ((11)C-(2b)) and used in vivo for microPET scanning and tissue metabolite identification. High PET signal was paralleled with the presence of radiolabeled (11)C-(2b)-6-O-sulfate and the SULT1E1 protein detected by western blot. Because this and other members of this family presenting specificity for SULT1E1 can be labeled with carbon-11 or fluorine-18, in vivo assays of SULT1E1 functional activity are now feasible in humans. PMID- 20304799 TI - Broad specificity AhpC-like peroxiredoxin and its thioredoxin reductant in the sparse antioxidant defense system of Treponema pallidum. AB - Little is known about the mechanisms by which Treponema pallidum (Tp), the causative agent of syphilis, copes with oxidative stress as it establishes persistent infection within its obligate human host. The Tp genomic sequence indicates that the bacterium's antioxidant defenses do not include glutathione and are limited to just a few proteins, with only one, TP0509, offering direct defense against peroxides. Although this Tp peroxiredoxin (Prx) closely resembles AhpC-like Prxs, Tp lacks AhpF, the typical reductant for such enzymes. Functionally, TpAhpC resembles largely eukaryotic, nonAhpC typical 2-Cys Prx proteins in using thioredoxin (Trx, TP0919) as an efficient electron donor and exhibiting broad specificity toward hydroperoxide substrates. Unlike many of the eukaryotic Prxs, however, TpAhpC is relatively resistant to inactivation during turnover with hydroperoxide substrates. As is often observed in typical 2-Cys Prxs, TpAhpC undergoes redox-sensitive oligomer formation. Quantitative immunoblotting revealed that TpTrx and TpAhpC are present at very high levels (over 100 and 300 microM, respectively) in treponemes infecting rabbit testes; their redox potentials, at -242 +/- 1 and -192 +/- 2 mV, respectively, are consistent with the role of TpTrx as the cellular reductant of TpAhpC. Transcriptional analysis of select antioxidant genes confirmed the presence of high mRNA levels for ahpC and trx which diminish greatly when spirochetes replicate under in vitro growth conditions. Thus, T. pallidum has evolved an extraordinarily robust, broad-spectrum AhpC as its sole mechanism for peroxide defense to combat this significant threat to treponemal growth and survival during infection. PMID- 20304800 TI - Metal-insulator quantum critical point beneath the high Tc superconducting dome. AB - An enduring question in correlated systems concerns whether superconductivity is favored at a quantum critical point (QCP) characterized by a divergent quasiparticle effective mass. Despite such a scenario being widely postulated in high T(c) cuprates and invoked to explain non-Fermi liquid transport signatures, experimental evidence is lacking for a critical divergence under the superconducting dome. We use ultrastrong magnetic fields to measure quantum oscillations in underdoped YBa(2)Cu(3)O(6+x), revealing a dramatic doping dependent upturn in quasiparticle effective mass at a critical metal-insulator transition beneath the superconducting dome. Given the location of this QCP under a plateau in T(c) in addition to a postulated QCP at optimal doping, we discuss the intriguing possibility of two intersecting superconducting subdomes, each centered at a critical Fermi surface instability. PMID- 20304801 TI - Nanoprobe measurements of materials at megabar pressures. AB - The use of nanoscale x-ray probes overcomes several key limitations in the study of materials up to multimegabar (> 200) pressures, namely, the spatial resolution of measurements of multiple samples, stress gradients, and crystal domains in micron to submicron size samples in diamond-anvil cells. Mixtures of Fe, Pt, and W were studied up to 282 GPa with 250-600 nm size synchrotron x-ray absorption and diffraction probes. The probes readily resolve signals from individual materials, between sample and gasket, and peak pressures, in contrast to the 5 microm-sized x-ray beams that are now becoming routine. The use of nanoscale x ray beams also enables single-crystal x-ray diffraction studies in nominally polycrystalline samples at ultrahigh pressures, as demonstrated in measurements of (Mg,Fe)SiO(3) postperovskite. These capabilities have potential for driving a push toward higher maximum pressures and further miniaturization of high-pressure devices, in the process advancing studies at extreme conditions. PMID- 20304802 TI - Revision of the mtDNA tree and corresponding haplogroup nomenclature. PMID- 20304803 TI - Circadian control of XPA and excision repair of cisplatin-DNA damage by cryptochrome and HERC2 ubiquitin ligase. AB - Cisplatin is one of the most commonly used anticancer drugs. It kills cancer cells by damaging their DNA, and hence cellular DNA repair capacity is an important determinant of its efficacy. Here, we investigated the repair of cisplatin-induced DNA damage in mouse liver and testis tissue extracts prepared at regular intervals over the course of a day. We find that the XPA protein, which plays an essential role in repair of cisplatin damage by nucleotide excision repair, exhibits circadian oscillation in the liver but not in testis. Consequently, removal of cisplatin adducts in liver extracts, but not in testis extracts, exhibits a circadian pattern with zenith at approximately 5 pm and nadir at approximately 5 am. Furthermore, we find that the circadian oscillation of XPA is achieved both by regulation of transcription by the core circadian clock proteins including cryptochrome and by regulation at the posttranslational level by the HERC2 ubiquitin ligase. These findings may be used as a guide for timing of cisplatin chemotherapy. PMID- 20304804 TI - Particle size and activation threshold: a new dimension of danger signaling. AB - Previous studies have shown that single-stranded RNA (ssRNA) mixed with protamine forms particles and activates immune cells through Toll-like receptors (TLRs). We have found that the size of protamine-RNA particles generated depends on the electrolyte content when mixing the 2 components. Moreover, we have evidenced that (1) nanometric particles induce production of interferon-alpha, whereas (2) micrometric particles mainly induce production of tumor necrosis factor-alpha (TNF-alpha) in human immune cells. We found that the mechanisms underlying these observations are (1) nanoparticles but not microparticles are selectively phagocytosed by plasmacytoid dendritic cells (pDCs), which produce interferon alpha and (2) monocytes that produce TNF-alpha have a higher activation threshold than that of pDCs. Thus, at the same time as sensing pathogen-associated molecular patterns such as ssRNA, the immune system distinguishes the size of the associated structure in such a way as to trigger the adapted antivirus (nanometric) or antibacterial/antifungal (micrometric) immune response. Our results introduce a new dimension in danger signaling--how size qualitatively affects innate response. PMID- 20304805 TI - The JAK2 46/1 haplotype predisposes to MPL-mutated myeloproliferative neoplasms. AB - The 46/1 JAK2 haplotype predisposes to V617F-positive myeloproliferative neoplasms, but the underlying mechanism is obscure. We analyzed essential thrombocythemia patients entered into the PT-1 studies and, as expected, found that 46/1 was overrepresented in V617F-positive cases (n = 404) versus controls (n = 1492, P = 3.9 x 10(-11)). The 46/1 haplotype was also overrepresented in cases without V617F (n = 347, P = .009), with an excess seen for both MPL exon 10 mutated and V617F, MPL exon 10 nonmutated cases. Analysis of further MPL positive, V617F-negative cases confirmed an excess of 46/1 (n = 176, P = .002), but no association between MPL mutations and MPL haplotype was seen. An excess of 46/1 was also seen in JAK2 exon 12 mutated cases (n = 69, P = .002), and these mutations preferentially arose on the 46/1 chromosome (P = .029). No association between 46/1 and clinical or laboratory features was seen in the PT-1 cohort either with or without V617F. The excess of 46/1 in JAK2 exon 12 cases is compatible with both the "hypermutability" and "fertile ground" hypotheses, but the excess in MPL-mutated cases argues against the former. No difference in sequence, splicing, or expression of JAK2 was found on 46/1 compared with other haplotypes, suggesting that any functional difference of JAK2 on 46/1, if it exists, must be relatively subtle. PMID- 20304806 TI - SNP array analysis in hematologic malignancies: avoiding false discoveries. AB - Comprehensive analysis of the cancer genome has become a standard approach to identifying new disease loci, and ultimately will guide therapeutic decisions. A key technology in this effort, single nucleotide polymorphism arrays, has been applied in hematologic malignancies to detect deletions, amplifications, and loss of heterozygosity (LOH) at high resolution. An inherent challenge of such studies lies in correctly distinguishing somatically acquired, cancer-specific lesions from patient-specific inherited copy number variations or segments of homozygosity. Failure to include appropriate normal DNA reference samples for each patient in retrospective or prospective studies makes it difficult to identify small somatic deletions not evident by standard cytogenetic analysis. In addition, the lack of proper controls can also lead to vastly overestimated frequencies of LOH without accompanying loss of DNA copies, so-called copy neutral LOH. Here we use examples from patients with myeloid malignancies to demonstrate the superiority of matched tumor and normal DNA samples (paired studies) over multiple unpaired samples with respect to reducing false discovery rates in high-resolution single nucleotide polymorphism array analysis. Comparisons between matched tumor and normal samples will continue to be critical as the field moves from high resolution array analysis to deep sequencing to detect abnormalities in the cancer genome. PMID- 20304807 TI - Pain-related behaviors and neurochemical alterations in mice expressing sickle hemoglobin: modulation by cannabinoids. AB - Sickle cell disease causes severe pain. We examined pain-related behaviors, correlative neurochemical changes, and analgesic effects of morphine and cannabinoids in transgenic mice expressing human sickle hemoglobin (HbS). Paw withdrawal threshold and withdrawal latency (to mechanical and thermal stimuli, respectively) and grip force were lower in homozygous and hemizygous Berkley mice (BERK and hBERK1, respectively) compared with control mice expressing human hemoglobin A (HbA-BERK), indicating deep/musculoskeletal and cutaneous hyperalgesia. Peripheral nerves and blood vessels were structurally altered in BERK and hBERK1 skin, with decreased expression of mu opioid receptor and increased calcitonin gene-related peptide and substance P immunoreactivity. Activators of neuropathic and inflammatory pain (p38 mitogen-activated protein kinase, STAT3, and mitogen-activated protein kinase/extracellular signal regulated kinase) showed increased phosphorylation, with accompanying increase in COX-2, interleukin-6, and Toll-like receptor 4 in the spinal cord of hBERK1 compared with HbA-BERK. These neurochemical changes in the periphery and spinal cord may contribute to hyperalgesia in mice expressing HbS. In BERK and hBERK1, hyperalgesia was markedly attenuated by morphine and cannabinoid receptor agonist CP 55940. We show that mice expressing HbS exhibit characteristics of pain observed in sickle cell disease patients, and neurochemical changes suggestive of nociceptor and glial activation. Importantly, cannabinoids attenuate pain in mice expressing HbS. PMID- 20304808 TI - Optimizing patient selection for myeloablative allogeneic hematopoietic cell transplantation in chronic myeloid leukemia in chronic phase. AB - Outstanding results have been obtained in the treatment of chronic myeloid leukemia (CML) with first-line imatinib therapy. However, approximately 35% of patients will not obtain long-term benefit with this approach. Allogeneic hematopoietic stem cell transplantation (HCT) is a valuable second- and third line therapy for appropriately selected patients. To identify useful prognostic indicators of transplantation outcome in postimatinib therapeutic interventions, we investigated the role of the HCT comorbidity index (HCT-CI) together with levels of C-reactive protein (CRP) before HCT in 271 patients who underwent myeloablative HCT for CML in first chronic phase. Multivariate analysis showed both an HCT-CI score higher than 0 and CRP levels higher than 9 mg/L independently predict inferior survival and increased nonrelapse mortality at 100 days after HCT. CML patients without comorbidities (HCT-CI score 0) with normal CRP levels (0-9 mg/L) may therefore be candidates for early allogeneic HCT after failing imatinib. PMID- 20304809 TI - Clinical significance of low levels of minimal residual disease at the end of remission induction therapy in childhood acute lymphoblastic leukemia. AB - Minimal residual disease (MRD) at the end of remission-induction therapy predicts relapse in acute lymphoblastic leukemia (ALL). We examined the clinical significance of levels below the usual threshold value for MRD positivity (0.01%) in 455 children with B-lineage ALL, using polymerase chain reaction amplification of antigen-receptor genes capable of detecting at least 1 leukemic cell per 100 000 normal mononucleated cells (0.001%). Of the 455 clinical samples studied on day 46 of therapy, 139 (30.5%) had MRD 0.001% or more with 63 of these (45.3%) showing levels of 0.001% to less than 0.01%, whereas 316 (69.5%) had levels that were either less than 0.001% or undetectable. MRD measurements of 0.001% to less than 0.01% were not significantly related to presenting characteristics but were associated with a poorer leukemia cell clearance on day 19 of remission induction therapy. Patients with this low level of MRD had a 12.7% (+/- 5.1%; SE) cumulative risk of relapse at 5 years, compared with 5.0% (+/- 1.5%) for those with lower or undetectable MRD (P < .047). Thus, low levels of MRD (0.001%-< 0.01%) at the end of remission induction therapy have prognostic significance in childhood ALL, suggesting that patients with this finding should be monitored closely for adverse events. PMID- 20304810 TI - Cross talk between the bone and immune systems: osteoclasts function as antigen presenting cells and activate CD4+ and CD8+ T cells. AB - The bone and immune systems are closely related through cellular and molecular interactions. Because bone-resorbing osteoclasts (OCs) are derived from the monocyte/macrophage lineage, similar to dendritic cells (DCs), we hypothesized that OCs could serve as antigen-presenting cells (APCs) to activate T cells. In this study, OCs were generated from human monocytes with stimulation by receptor activator of nuclear factor kappaB ligand (RANKL) and macrophage colony stimulating factor (M-CSF). Results showed that, similar to DCs, OCs express major histocompatibility complex (MHC) classes I and II, and CD80, CD86, and CD40; and uptake soluble antigens. OCs secrete interleukin-10 (IL-10), transforming growth factor-beta (TGF-beta), IL-6, and tumor necrosis factor-alpha (TNF-alpha), but not IL-12p70. OCs present allogeneic antigens and activate both CD4+ and CD8+ alloreactive T cells in an MHC-restricted fashion. OCs also present soluble protein tetanus toxoid to activate autologous CD4+ T cells. These findings indicate that OCs can function as APCs and activate both CD4+ and CD8+ T cells. Thus, our study provides new insight into the effect of OCs on the immune system and may help develop novel strategies for treating diseases such as rheumatoid arthritis and multiple myeloma, which affect both the bone and immune systems. PMID- 20304811 TI - Weight loss in obese C57BL/6 mice limits adventitial expansion of established angiotensin II-induced abdominal aortic aneurysms. AB - Previous studies demonstrated that obesity increases inflammation in periaortic adipose tissue and promotes angiotensin II (ANG II)-induced abdominal aortic aneurysms (AAAs). We sought to determine whether weight loss of obese C57BL/6 mice would influence the progression of established AAAs. Male C57BL/6 mice were fed a high-fat diet (HF) for 4 mo and then infused with either saline or ANG II (1,000 ng x kg(-1) x min(-1)) for 3 mo. Mice with dilated suprarenal aortas at 28 days of ANG II infusion were designated to groups fed the HF (HF/HF) or a low-fat diet (LF; 10% kcal as fat; HF/LF) to induce weight loss for the last 2 mo of infusions. Suprarenal aortic lumen diameters of obese mice were increased by ANG II infusion at day 28 (day 0: 1.03 + or - 0.02; day 28: 1.86 + or - 0.14 mm; P < 0.05), but did not progress with continued infusion in HF/HF mice. Moreover, aortic lumen diameters were not different between groups (HF/HF: 1.89 + or - 0.15; HF/LF: 1.79 + or - 0.18 mm). However, maximal diameters of excised AAAs were decreased with weight loss (HF/HF: 2.00 + or - 0.11; HF/LF: 1.55 + or - 0.13 mm; P < 0.05) and had reduced adventitial areas (HF/HF: 1.18 + or - 0.10; HF/LF: 0.54 + or - 0.02 mm(2); P < 0.05). Neovascularization of aortic adventitias was strikingly decreased in HF/LF mice (HF/HF: 43 + or - 5; HF/LF: 12 + or - 2 endothelial cells/adventitial area; P < 0.05). ANG II-induced elevations in adipose mRNA abundance of CD105, an adipose-derived stem cell marker, were abolished with weight loss. These results demonstrate that weight loss limits adventitial expansion of ANG II-induced AAAs. Reduced neovascularization from weight loss may limit progression of AAAs. PMID- 20304813 TI - Roles for Nox4 in the contractile response of bovine pulmonary arteries to hypoxia. AB - Hypoxia appears to promote contraction [hypoxic pulmonary vasoconstriction (HPV)] of bovine pulmonary arteries (BPA) through removal of a peroxide-mediated relaxation. This study examines the roles of BPA Nox oxidases and mitochondria in the HPV response. Inhibitors of Nox2 (0.1 mM apocynin and 50 muM gp91-dstat) and mitochondrial electron transport (10 muM antimycin and rotenone) decreased superoxide generation in BPA without affecting contraction to 25 mM KCl or the HPV response. Transfection of BPA with small inhibitory RNA (siRNA) for Nox2 and Nox4 decreased Nox2 and Nox4 protein expression, respectively, associated with an attenuation of superoxide detection, without affecting 25 mM KCl contraction. However, Nox4 siRNA, but not Nox2, attenuated HPV in BPA. A Nox4 inhibitor plumbagin (10 muM) increased basal force, decreased superoxide detection and peroxide release, and caused BPA to relax under hypoxia. Although acute removal of peroxide with 0.1 mM ebselen increased 25 mM KCl contraction and decreased hypoxic contraction, prolonged treatment with ebselen only decreased hypoxic contraction without affecting 25 mM KCl contraction, suggesting basal peroxide levels also maintain a contractile mechanism not removed by acute hypoxia. Organ culture of BPA with transforming growth factor (TGF)-beta1 (4 nM) increased Nox4 expression, superoxide, peroxide, and the HPV response. Thus Nox2 and mitochondria are sources for superoxide generation in BPA, which do not appear to influence the HPV response. However, peroxide derived from superoxide generated by Nox4 appears to maintain a basal relaxation in BPA under normoxic conditions, which is removed under hypoxia leading to HPV. Peroxide generated by Nox4 may also function to maintain a contractile mechanism, which is not reversed by acute hypoxia. PMID- 20304814 TI - Role of Ca(2+)/calmodulin-dependent protein kinase II in the regulation of the cardiac L-type Ca(2+) current during endothelin-1 stimulation. AB - Endothelin-1 (ET-1) shows a positive inotropic effect on cardiac muscle. Although the L-type Ca(2+) current (I(Ca)) is one of the important determinants of cardiac excitation-contraction coupling, the effect of ET-1 on the I(Ca) is not always clear. The controversial results appear to be due to different patch-clamp methods. The present study measured the effect of ET-1 on the I(Ca) of rat ventricular myocytes using the perforated patch-clamp technique. The holding potential was set to -40 mV, and depolarization was applied every 10 s. ET-1 (10 nM) increased the I(Ca) in a monophasic manner. The current reached a steady state 15 min after the application of ET-1, when the measurement was done. Endothelin receptor subtype expression was also investigated using Western immunoblotting. ET(A)-receptor protein was expressed, but ET(B)-receptor protein was not expressed, in the cell membranes of rat ventricular myocytes. The effect of ET-1 on the I(Ca) was inhibited by a selective ET(A)-receptor antagonist, BQ 123, but not by a selective ET(B)-receptor antagonist, BQ-788. The effect was inhibited by protein kinase C (PKC) inhibitor chelerythrine and Ca(2+)/calmodulin dependent protein kinase II (CaMKII) inhibitor KN-93, but not by its inactive analog KN-92. The effect of ET-1 was also blocked by another CaMKII inhibitor, autocamtide-2-related inhibitory peptide. These results suggest that ET-1 increases the I(Ca) via the ET(A)-receptor-PKC-CaMKII pathway. PMID- 20304812 TI - Physical activity maintains aortic endothelium-dependent relaxation in the obese type 2 diabetic OLETF rat. AB - We tested the hypothesis that physical activity can attenuate the temporal decline of ACh-induced endothelium-dependent relaxation during type 2 diabetes mellitus progression in the Otsuka Long-Evans Tokushima fatty (OLETF) rat. Sedentary OLETF rats exhibited decreased ACh-induced abdominal aortic endothelium dependent relaxation from 13 to 20 wk of age (20-35%) and from 13 to 40 wk of age (35-50%). ACh-induced endothelium-dependent relaxation was maintained in the physically active OLETF group and control sedentary Long-Evans Tokushima Otsuka (LETO) group from 13 to 40 wk of age. Aortic pretreatment with N(G)-nitro-l arginine (l-NNA), indomethacin (Indo), and l-NNA + Indo did not alter the temporal decline in ACh-induced endothelium-dependent relaxation. Temporal changes in the protein expression of SOD isoforms in the aortic endothelium or smooth muscle did not contribute to the temporal decline in ACh-induced endothelium-dependent relaxation in sedentary OLETF rats. A significant increase in the 40-wk-old sedentary LETO and physically active OLETF rat aortic phosphorylated endothelial nitric oxide (p-eNOS)-to-eNOS ratio was observed versus 13- and 20-wk-old rats in each group that was not seen in the 40- versus 13- and 20-wk-old sedentary OLETF rats. These results suggest that temporal changes in the antioxidant system, EDHF, and cycloxygenase metabolite production in sedentary OLETF rat aortas do not contribute to the temporal decline in sedentary OLETF rat aortic ACh-induced endothelium-dependent relaxation seen with type 2 diabetes mellitus progression. We also report that physical activity in conjunction with aging in the OLETF rat results in a temporal increase in the aortic endothelial p-eNOS-to-eNOS ratio that was not seen in sedentary OLETF rats. These results suggest that the sustained aortic ACh-induced endothelium dependent relaxation in aged physically active OLETF rats may be the result of an increase in active aortic eNOS. PMID- 20304815 TI - MnSOD protects against COX1-mediated endothelial dysfunction in chronic heart failure. AB - Endothelial function is impaired by oxidative stress in chronic heart failure (HF). Mechanisms that protect against increases in oxidative stress in HF are not clear. The goal of this study was to determine whether manganese superoxide dismutase (MnSOD) plays a key role in protecting against endothelial dysfunction in HF. Endothelial function and gene expression were examined in aorta from wild type mice (MnSOD(+/+)) and mice deficient in MnSOD (MnSOD(+/-)) 12 wk after ligation of the left coronary artery (LCA). LCA ligation produced similar size myocardial infarctions in MnSOD(+/+) and MnSOD(+/-) mice and reduced ejection fraction to approximately 20% in both groups. Maximal relaxation in response to acetylcholine was 78 +/- 3% (mean +/- SE) and 66 +/- 8% in sham-operated MnSOD(+/+) and MnSOD(+/-) mice, respectively. Expression of antioxidant enzymes increased in MnSOD(+/+) mice with HF, and maximal relaxation to acetylcholine was slightly impaired (68 +/- 4%). Greater endothelial dysfunction was observed in MnSOD(+/-) mice with HF (46 +/- 5%, P < 0.05), which was significantly improved by polyethylene glycol-catalase but not Tempol. Incubation with the nonspecific cyclooxygenase (COX) inhibitor indomethacin or the COX1 inhibitor valeryl salicylate, but not the COX-2 inhibitor NS-398, significantly improved relaxation to acetylcholine in HF mice (maximum relaxation = 74 +/- 5, 91 +/- 1, and 58 +/- 5%). These data suggest that MnSOD plays a key role in protecting against endothelial dysfunction in HF. A novel mechanism was identified whereby chronic increases in oxidative stress, produced by mitochondrial SOD deficiency, impair vascular function via a hydrogen peroxide-dependent, COX1-dependent, endothelium derived contracting factor. PMID- 20304817 TI - Cardiac oxidative stress is involved in heart failure induced by thiamine deprivation in rats. AB - Thiamine is an important cofactor of metabolic enzymes, and its deficiency leads to cardiovascular dysfunction. First, we characterized the metabolic status measuring resting oxygen consumption rate and lactate blood concentration after 35 days of thiamine deficiency (TD). The results pointed to a decrease in resting oxygen consumption and a twofold increase in blood lactate. Confocal microscopy showed that intracellular superoxide (approximately 40%) and H(2)O(2) (2.5 times) contents had been increased. In addition, biochemical activities and protein expression of SOD, glutathione peroxidase, and catalase were evaluated in hearts isolated from rats submitted to thiamine deprivation. No difference in SOD activity was detected, but protein levels were found to be increased. Catalase activity increased 2.1 times in TD hearts. The observed gain in activity was attended by an increased catalase protein level. However, a marked decrease in glutathione peroxidase activity (control 435.3 + or - 28.6 vs. TD 199.4 + or - 30.2 nmol NADPH x min(-1) x ml(-1)) was paralleled by a diminution in the protein levels. Compared with control hearts, we did observe a greater proportion of apoptotic myocytes by TdT-mediated dUTP nick end labeling (TUNEL) and caspase-3 reactivity techniques. These results indicate that during TD, reactive oxygen species (ROS) production may be enhanced as a consequence of the installed acidosis. The perturbation in the cardiac myocytes redox balance was responsible for the increase in apoptosis. PMID- 20304816 TI - Isoform- and tissue-specific regulation of the Ca(2+)-sensitive transcription factor NFAT in cardiac myocytes and heart failure. AB - Nuclear factors of activated T cells (NFATs) are Ca(2+)-sensitive transcription factors that have been implicated in hypertrophy, heart failure (HF), and arrhythmias. Cytosolic NFAT is activated by dephosphorylation by the Ca(2+) sensitive phosphatase calcineurin, resulting in translocation to the nucleus, which is opposed by kinase activity, rephosphorylation, and nuclear export. Four different NFAT isoforms are expressed in the heart. The activation and regulation of NFAT in adult cardiac myocytes, which may depend on the NFAT isoform and cell type, are not fully understood. This study compared basal localization, import, and export of NFATc1 and NFATc3 in adult atrial and ventricular myocytes to identify isoform- and tissue-specific regulatory mechanisms of NFAT activation under physiological conditions and in HF. NFAT-green fluorescent protein fusion proteins and NFAT immunocytochemistry were used to analyze NFAT regulation in adult cat and rabbit myocytes. NFATc1 displayed basal nuclear localization in atrial and ventricular myocytes, an effect that was attenuated by reducing intracellular Ca(2+) concentration and inhibiting calcineurin, and enhanced by the inhibition of nuclear export. In contrast, NFATc3 was localized to the cytoplasm but could be driven to the nucleus by angiotensin II and endothelin-1 stimulation in atrial, but not ventricular, cells. Inhibition of nuclear export (by leptomycin B) facilitated nuclear localization in both cell types. Ventricular myocytes from HF rabbits showed increased basal nuclear localization of endogenous NFATc3 and reduced responsiveness of NFAT translocation to phenylephrine stimulation. In control myocytes, Ca(2+) overload, leading to spontaneous Ca(2+) waves, induced substantial translocation of NFATc3 to the nucleus. We conclude that the activation of NFAT in adult cardiomyocytes is isoform and tissue specific and is tightly controlled by nuclear export. NFAT is activated in myocytes from HF animals and may be secondary to Ca(2+) overload. PMID- 20304818 TI - Adrenal GRK2 lowering is an underlying mechanism for the beneficial sympathetic effects of exercise training in heart failure. AB - Exercise training has been reported to exert beneficial effects on cardiac function and to reduce morbidity and mortality of chronic heart failure (HF). Augmented sympathetic nervous system (SNS) activity, leading to elevated circulating catecholamine (CA) levels, is a hallmark of chronic HF that significantly aggravates this disease. Exercise training has been shown to also reduce SNS overactivity in HF, but the underlying molecular mechanism(s) remain unidentified. We recently reported that adrenal G protein-coupled receptor kinase 2 (GRK2), an enzyme that regulates the sympathoinhibitory alpha(2)-adrenoceptors (alpha(2)-ARs) present in the CA-producing adrenal medulla, is upregulated in HF, contributing to the chronically elevated CA levels and SNS activity of the disease. In the present study, we tested whether exercise training can affect the adrenal GRK2-alpha(2)-AR-CA production system in the context of HF. For this purpose, a 10-wk-long exercise training regimen of adult male Sprague-Dawley rats starting at 4 wk postmyocardial infarction (post-MI) was employed, and examination at the end of this treatment period revealed significant amelioration of beta-AR-stimulated contractility in response to exercise training, accompanied by cardiac GRK2 reduction and restoration of circulating plasma CA levels. Importantly, adrenal GRK2 expression (72 + or - 5% reduction vs. post-MI untrained) and alpha(2)-AR number were also restored after exercise training in post-MI animals. These results suggest that exercise training restores the adrenal GRK2-alpha(2)-AR-CA production axis, and this might be part of the mechanism whereby this therapeutic modality normalizes sympathetic overdrive and impedes worsening of the failing heart. PMID- 20304819 TI - Developmental aspects of cardiac Ca(2+) signaling: interplay between RyR- and IP(3)R-gated Ca(2+) stores. AB - The dominant mode of intracellular Ca(2+) release in adult mammalian heart is gated by ryanodine receptors (RyRs), but it is less clear whether inositol 1,4,5 trisphosphate (IP(3))-gated Ca(2+) release channels (IP(3)Rs), which are important during embryogenesis, play a significant role during early postnatal development. To address this question, we measured confocal two-dimensional Ca(2+) dependent fluorescence images in acutely isolated neonatal (days 1 to 2) and juvenile (days 8-10) rat cardiomyocytes, either voltage-clamped or permeabilized, where rapid exchange of solution could be used to selectively activate the two types of Ca(2+) release channel. Targeting RyRs with caffeine produced large and rapid Ca(2+) signals throughout the cells. Application of ATP and endothelin-1 to voltage-clamped, or IP(3) to permeabilized, cells produced smaller and slower Ca(2+) signals that were most prominent in subsarcolemmal regions and were suppressed by either the IP(3)R-blocker 2 aminoethoxydiphenylborate or replacement of the biologically active form of IP(3) with its L-stereoisomer. Such IP(3)R-gated Ca(2+) releases were amplified by Ca(2+)-induced Ca(2+) release (CICR) via RyRs since they were also reduced by compounds that block the RyRs (tetracaine) or deplete the Ca(2+) pools they gate (caffeine, ryanodine). Spatial analysis revealed both subsarcolemmal and perinuclear origins for the IP(3)-mediated Ca(2+) release events RyR- and IP(3)R gated Ca(2+) signals had larger magnitudes in juvenile than in neonatal cardiomyocytes. Ca(2+) signaling was generally quite similar in atrial and ventricular cardiomyocytes but showed divergent development of IP(3)-mediated regulation in juveniles. Our data suggest that an intermediate stage of Ca(2+) signaling may be present in developing cardiomyocytes, where, in addition to RyR gated Ca(2+) pools, IP(3)-gated Ca(2+) release is sufficiently large in magnitude and duration to trigger or contribute to activation of CICR and cardiac contraction. PMID- 20304821 TI - Measurements of changes in left ventricular volume, strain, and twist during isovolumic relaxation using MRI. AB - Left ventricular (LV) active relaxation begins before aortic valve closure and is largely completed during isovolumic relaxation (IVR), before mitral valve opening. During IVR, despite closed mitral and aortic valves, indirect assessments of LV volume have suggested volume increases during this period. The aim of this study is to measure LV volume throughout IVR and to determine the sources of any volume changes. For 10 healthy individuals (26.0 + or - 3.8 yr), magnetic resonance imaging was used to measure time courses of LV volume, principal myocardial strains (circumferential, longitudinal, radial), and LV twist. Mitral leaflet motion was observed using echocardiography. During IVR, LV volume measurements showed an apparent increase of 4.6 + or - 1.5 ml (5.0 + or - 2.0% of the early filling volume change), the LV untwisted by 4.5 + or - 1.9 degrees (36.6 + or - 18.0% of peak systolic twist), and changes in circumferential, longitudinal, and radial strains were +0.87 + or - 0.64%, +0.93 + or - 0.57%, and -1.46 + or - 1.66% (4.2 + or - 3.3%, 5.9 + or - 3.3%, and 5.3 + or - 7.5% of peak systolic strains), respectively. The apparent changes in volume correlated (P < 0.01) with changes in circumferential, longitudinal, and radial strains (r = 0.86, 0.69, and -0.37, respectively) and untwisting (r = 0.83). The closed mitral valve leaflets were observed to descend into the LV throughout IVR in all subjects in apical four- and three-chamber and parasternal long-axis views by 6.0 + or - 3.3, 5.1 + or - 2.4, and 2.1 + or - 5.0 mm, respectively. In conclusion, LV relaxation during IVR is associated with changes in principal strains and untwisting, which are all correlated with an apparent increase in LV volume. Since closed mitral and aortic valves ensure true isovolumic conditions, the apparent volume change likely reflects expansion of the LV myocardium and the inward bowing of the closed mitral leaflets toward the LV interior. PMID- 20304820 TI - The p75 neurotrophin receptor, semaphorins, and sympathetic traffic in the heart. PMID- 20304822 TI - Activating transcription factor 3 is a positive regulator of human IFNG gene expression. AB - IL-12 and IL-18 are essential for Th1 differentiation, whereas the role of IFN alpha in Th1 development is less understood. In this microarray-based study, we searched for genes that are regulated by IFN-alpha, IL-12, or the combination of IL-12 plus IL-18 during the early differentiation of human umbilical cord blood CD4(+) Th cells. Twenty-six genes were similarly regulated in response to treatment with IL-12, IFN-alpha, or the combination of IL-12 plus IL-18. These genes could therefore play a role in Th1 lineage decision. Transcription factor activating transcription factor (ATF) 3 was upregulated by these cytokines and selected for further study. Ectopic expression of ATF3 in CD4(+) T cells enhanced the production of IFN-gamma, the hallmark cytokine of Th1 cells, whereas small interfering RNA knockdown of ATF3 reduced IFN-gamma production. Furthermore, ATF3 formed an endogenous complex with JUN in CD4(+) T cells induced to Th1. Chromatin immunoprecipitation and luciferase reporter assays showed that both ATF3 and JUN are recruited to and transactivate the IFNG promoter during early Th1 differentiation. Collectively, these data indicate that ATF3 promotes human Th1 differentiation. PMID- 20304824 TI - Soluble IL-7R alpha (sCD127) inhibits IL-7 activity and is increased in HIV infection. AB - Soluble CD127 (sCD127) appears to play an important role in the immunopathogenesis of several chronic infections, multiple sclerosis, and various cancers. The function of sCD127 and whether it influences IL-7 bioavailability or activity is unknown. In this study, we demonstrated that recombinant and native sources of sCD127 significantly inhibited IL-7-mediated STAT5 and Akt phosphorylation in CD8(+) T cells. IL-7-mediated proliferation and Bcl-2 expression were similarly reduced by sCD127. In each case, native sCD127 inhibited IL-7 activity to a greater degree than rsCD127. Anti-IL-7 activity was inherent to human plasma and could be reversed by depletion of CD127, revealing for the first time the biological activity of naturally occurring sCD127. Plasma sCD127 concentrations were increased in HIV(+) individuals compared with HIV(-) controls, correlated with IL-7 levels, and remained unchanged in HIV(+) individuals following 1 y of effective antiretroviral therapy. Determining the regulation and function of sCD127 may be critical for understanding both the pathogenesis of diseases in which IL-7 likely has a role (e.g., HIV infection, cancer) and its potential impact on IL-7 as a therapeutic approach. PMID- 20304823 TI - IL-4 and TGF-beta 1 counterbalance one another while regulating mast cell homeostasis. AB - Mast cell responses can be altered by cytokines, including those secreted by Th2 and regulatory T cells (Treg). Given the important role of mast cells in Th2 mediated inflammation and recent demonstrations of Treg-mast cell interactions, we examined the ability of IL-4 and TGF-beta1 to regulate mast cell homeostasis. Using in vitro and in vivo studies of mouse and human mast cells, we demonstrate that IL-4 suppresses TGF-beta1 receptor expression and signaling, and vice versa. In vitro studies demonstrated that IL-4 and TGF-beta1 had balancing effects on mast cell survival, migration, and FcepsilonRI expression, with each cytokine cancelling the effects of the other. However, in vivo analysis of peritoneal inflammation during Nippostrongylus brasiliensis infection in mice revealed a dominant suppressive function for TGF-beta1. These data support the existence of a cytokine network involving the Th2 cytokine IL-4 and the Treg cytokine TGF beta1 that can regulate mast cell homeostasis. Dysregulation of this balance may impact allergic disease and be amenable to targeted therapy. PMID- 20304825 TI - Human plasmacytoid dendritic cells phagocytose, process, and present exogenous particulate antigen. AB - Plasmacytoid dendritic cells (pDCs) play a major role in shaping both innate and adaptive immune responses, mainly via their production of large amounts of type I IFNs. pDCs are considered to primarily present endogenous Ags and are thought not to participate in the uptake and presentation of Ags from the extracellular environment, in contrast to their myeloid counterparts, which efficiently endocytose extracellular particulates. In this study, we show that human pDCs are able to phagocytose and process particulate forms of Ag entrapped in poly(lactic coglycolic acid) microparticles. Furthermore, pDCs were also able to sense TLR ligands (TLR-Ls) incorporated in these particles, resulting in rapid pDC activation and high IFN-alpha secretion. Combining a tetanus toxoid peptide and TLR-Ls (CpG C and R848) in these microparticles resulted in efficient pDC activation and concomitant Ag-specific T cell stimulation. Moreover, particulate Ag was phagocytosed and presented more efficiently than soluble Ag, indicating that microparticles can be exploited to facilitate efficient delivery of antigenic cargo and immunostimulatory molecules to pDCs. Together, our results show that in addition to their potency to stimulate innate immunity, pDCs can polarize adaptive immune responses against exogenous particulate Ag. These results may have important consequences for the development of new immunotherapeutic strategies exploiting Ag and TLR-Ls encapsulated in microparticles to target APC subsets. PMID- 20304826 TI - Estradiol and G1 reduce infarct size and improve immunosuppression after experimental stroke. AB - Reduced risk and severity of stroke in adult females is thought to depend on normal endogenous levels of estrogen, a well-known neuroprotectant and immunomodulator. In male mice, experimental stroke induces immunosuppression of the peripheral immune system, characterized by a reduction in spleen size and cell numbers and decreased cytokine and chemokine expression. However, stroke induced immunosuppression has not been evaluated in female mice. To test the hypothesis that estradiol (E2) deficiency exacerbates immunosuppression after focal stroke in females, we evaluated the effect of middle cerebral artery occlusion on infarct size and peripheral and CNS immune responses in ovariectomized mice with or without sustained, controlled levels of 17-beta-E2 administered by s.c. implant or the putative membrane estrogen receptor agonist, G1. Both E2- and G1-replacement decreased infarct volume and partially restored splenocyte numbers. Moreover, E2-replacement increased splenocyte proliferation in response to stimulation with anti-CD3/CD28 Abs and normalized aberrant mRNA expression for cytokines, chemokines, and chemokine receptors and percentage of CD4(+)CD25(+)FoxP3(+) T regulatory cells observed in E2-deficient animals. These beneficial changes in peripheral immunity after E2 replacement were accompanied by a profound reduction in expression of the chemokine, MIP-2, and a 40-fold increased expression of CCR7 in the lesioned brain hemisphere. These results demonstrate for the first time that E2 replacement in ovariectomized female mice improves stroke-induced peripheral immunosuppression. PMID- 20304827 TI - PU.1 positively regulates GATA-1 expression in mast cells. AB - Coexpression of PU.1 and GATA-1 is required for proper specification of the mast cell lineage; however, in the myeloid and erythroid lineages, PU.1 and GATA-1 are functionally antagonistic. In this study, we report a transcriptional network in which PU.1 positively regulates GATA-1 expression in mast cell development. We isolated a variant mRNA isoform of GATA-1 in murine mast cells that is significantly upregulated during mast cell differentiation. This isoform contains an alternatively spliced first exon (IB) that is distinct from the first exon (IE) incorporated in the major erythroid mRNA transcript. In contrast to erythroid and megakaryocyte cells, in mast cells we show that PU.1 and GATA-2 predominantly occupy potential cis-regulatory elements in the IB exon region in vivo. Using reporter assays, we identify an enhancer flanking the IB exon that is activated by PU.1. Furthermore, we observe that in PU.1(-/-) fetal liver cells, low levels of the IE GATA-1 isoform is expressed, but the variant IB isoform is absent. Reintroduction of PU.1 restores variant IB isoform and upregulates total GATA-1 protein expression, which is concurrent with mast cell differentiation. Our results are consistent with a transcriptional hierarchy in which PU.1, possibly in concert with GATA-2, activates GATA-1 expression in mast cells in a pathway distinct from that seen in the erythroid and megakaryocytic lineages. PMID- 20304830 TI - An alternative path for antigen presentation: group 1 CD1 proteins. PMID- 20304829 TI - Naive CD4+ T lymphocytes circulate through lymphoid organs to interact with endogenous antigens and upregulate their function. AB - Naive T lymphocytes recirculate through the lymph-vascular system and enter and exit lymphoid organs. Using mice expressing the photoconvertible fluorescence protein Kaede, we demonstrated that naive T cells seek to interact with endogenous Ags after migrating to the lymphoid organs. The interaction with endogenous Ags transiently induces CD69 expression on T cells, which prolongs retention in the lymphoid organs. Cells that fail to express CD69 or lose CD69 expression migrate to other lymphoid organs. Functionally, CD69(+)-naive CD4(+) T cells exhibit faster and greater cytokine production than do CD69(-) naive CD4(+) T cells. These results indicate that CD4(+) T cells continuously migrate to interact with endogenous Ags, and such an interaction plays an important role in the Ag reactivity of naive CD4(+) T cells. PMID- 20304828 TI - Role of SMAD and non-SMAD signals in the development of Th17 and regulatory T cells. AB - Whereas TGF-beta is essential for the development of peripherally induced Foxp3(+) regulatory T cells (iTreg cells) and Th17 cells, the intracellular signaling mechanism by which TGF-beta regulates development of both cell subsets is less understood. In this study, we report that neither Smad2 nor Smad3 gene deficiency abrogates TGF-beta-dependent iTreg induction by a deacetylase inhibitor trichostatin A in vivo, although the loss of the Smad2 or Smad3 gene partially reduces iTreg induction in vitro. Similarly, SMAD2 and SMAD3 have a redundant role in development of Th17 in vitro and in experimental autoimmune encephalomyelitis. In addition, ERK and/or JNK pathways were shown to be involved in regulating iTreg cells, whereas the p38 pathway predominately modulated Th17 and experimental autoimmune encephalomyelitis induction. Therefore, selective targeting of these intracellular TGF-beta signaling pathways during iTreg and Th17 cell development might lead to the development of therapies in treating autoimmune and other chronic inflammatory diseases. PMID- 20304831 TI - Recognition of Cluster of Differentiation 1 Antigens by Human CD4-CD8- CytolyticT Lymphocyte. Nature. 1989. 341: 447-450. 1989. PMID- 20304833 TI - Retraction: Activation of human oral epithelial cells by neutrophil proteinase 3 through protease-activated receptor-2. PMID- 20304832 TI - Translation control: a multifaceted regulator of inflammatory response. AB - A robust innate immune response is essential to the protection of all vertebrates from infection, but it often comes with the price tag of acute inflammation. If unchecked, a runaway inflammatory response can cause significant tissue damage, resulting in myriad disorders, such as dermatitis, toxic shock, cardiovascular disease, acute pelvic and arthritic inflammatory diseases, and various infections. To prevent such pathologies, cells have evolved mechanisms to rapidly and specifically shut off these beneficial inflammatory activities before they become detrimental. Our review of recent literature, including our own work, reveals that the most dominant and common mechanism is translational silencing, in which specific regulatory proteins or complexes are recruited to cis-acting RNA structures in the untranslated regions of single or multiple mRNAs that code for the inflammatory protein(s). Enhancement of the silencing function may constitute a novel pharmacological approach to prevent immunity-related inflammation. PMID- 20304834 TI - Retraction: Neutrophil serine proteinases activate human nonepithelial cells to produce inflammatory cytokines through protease-activated receptor 2. PMID- 20304835 TI - Retraction: Proinflammatory cytokines induce proteinase 3 as membrane-bound and secretory forms in human oral epithelial cells and antibodies to proteinase 3 activate the cells through protease-activated receptor-2. PMID- 20304836 TI - Persistence of muscle sympathetic nerve activity during vasovagal syncope. AB - AIMS: To determine whether sympathetic nerve firing to skeletal muscle vasculature is withdrawn during vasovagal syncope (VVS) precipitated by passive graded head-up tilt (HUT) table testing. METHODS AND RESULTS: We performed passive graded HUT table testing in 18 patients with a history of recurrent postural VVS whom we evaluated during the syncopal event. All patients developed typical VVS during testing. Blood pressure was measured continuously via intra brachial arterial line. Muscle sympathetic nerve activity (MSNA) was measured using an electrode in the peroneal nerve. Passive graded HUT was then applied. No pharmacological agents were used to provoke syncope. The recording site was maintained through the syncopal event in 10 of 18 patients and we were able to demonstrate persistence of MSNA during syncope in 9. The predominant haemodynamic pattern of syncope in this cohort was mixed--hypotension and bradycardia, with heart rate not falling <40 b.p.m. (n = 10). CONCLUSION: Our data challenge the established view that the final trigger for human orthostatic vasovagal reactions is sympathetic nervous system inhibition. Efferent sympathetic nerve traffic to the skeletal muscle vasculature was nearly always maintained through the faint. This finding supports an alternative viewpoint, that vasodilator mechanisms underlie the blood pressure fall in VVS. PMID- 20304837 TI - Gender differences in heart failure: paving the way towards personalized medicine? PMID- 20304838 TI - Recombinant apolipoprotein A-I Milano rapidly reverses aortic valve stenosis and decreases leaflet inflammation in an experimental rabbit model. AB - AIMS: Aortic stenosis (AS) is associated with significant morbidity and mortality. Recombinant apolipoprotein A-I Milano (rApoA-I(M)) induces atherosclerotic plaque regression. The aims of this study were to determine the effects of rApoA-I(M) on experimental aortic valve degeneration and its mechanisms of action. METHODS AND RESULTS: New Zealand White rabbits (n = 20) were fed an atherogenic diet for 9 months and then randomized to either placebo or rApoA-I(M). Echocardiography was used to assess the effect of the treatments on AS. Porcine aortic valve myofibroblasts (PAVMF) treated with oxidized low density lipoprotein served to define the effects of rApoA-I(M) on the expression of monocyte chemoattractant protein-1 (MCP-1), nuclear factor (NF)-kappaB, and alkaline phosphatase (AP). Recombinant apolipoprotein A-I Milano increased aortic valve area (AVA) by 32% (0.25 +/- 0.05 to 0.34 +/- 0.07 cm(2), P < 0.01); whereas AVA remained unchanged in the placebo group (0.24 +/- 0.05 to 0.26 +/- 0.04 cm(2), P = 0.58). Histopathological examination of aortic valves in the rApoA I(M) animals showed significantly less leaflet thickening, inflammation, and calcification vs. the placebo group. In vitro, rApoA-I(M) significantly inhibited MCP-1, AP, and NF-kappaB and decreased intracellular cholesterol content in PAVMF. CONCLUSION: Recombinant apolipoprotein A-I Milano treatment reverses AS in this experimental rabbit model. The beneficial effects seem to be mediated by enhanced cholesterol removal and by reduced inflammation and calcification. PMID- 20304839 TI - Diastolic dysfunction predicts new-onset atrial fibrillation and cardiovascular events in patients with acute myocardial infarction and depressed left ventricular systolic function: a CARISMA substudy. AB - AIMS: The aim of this study was to investigate the association between diastolic dysfunction and long-term occurrence of new-onset atrial fibrillation (AF) and cardiac events in patients with acute myocardial infarction (AMI) and left ventricular (LV) systolic dysfunction. METHODS AND RESULTS: The study was performed as a substudy on the CARISMA study population. The CARISMA study enrolled 312 patients with an AMI and LV ejection fraction 75, diabetes, hypertension, valve disease, prior stroke, or transient ischaemic attack and cardiomyopathy. A total of 635 procedures were performed. The incidence of thrombus was 12/635 (1.9%) despite therapeutic anti-coagulation. Patients with thrombus had larger LA diameter, mean 50.6+/-6.2 mm vs. 44.2+/-7.6 (P=0.006). In univariate analysis, persistent AF [odds ratio (OR)=10.4 with 95% CI 1.8-19.1], hypertension [OR=11.7 with 95% CI 2.5-54.1], age>75 (OR=4.5 with 95% CI 1.2-17.2), and cardiomyopathy (OR 5.9 with 95% CI 1.8-19.1) were significantly associated with thrombus. In multivariate analysis, hypertension (OR=14.2 with 95% CI 2.6-77.5), age>75 (OR=8.1, 95% CI 1.5-44.9), and cardiomyopathy (OR=10.5 with 95% CI 2.6-77.5) were independently associated with thrombus. There was no thrombus in patients without clinical risk factors. CONCLUSION: In patients presenting for AF ablation, LA thrombus is only seen in those with clinical risk factors. TOE is indicated in this group but may be unnecessary in patients without clinical risk factors. PMID- 20304843 TI - Timing of revascularization after acute myocardial infarction. AB - The optimal timing of surgical revascularization after acute myocardial infarction remains controversial. Higher mortality after emergency coronary artery bypass has been documented. We retrospectively reviewed 278 patients who underwent coronary artery bypass between 2005 and 2007. The time from onset of myocardial infarction to surgical revascularization was the basis for dividing patients into 3 groups: surgery was performed within 24 h in group 1, at 24-72 h in group 2, and after 14 days in group 3. There was a definite relationship between the timing of revascularization and the outcome of surgery. Group 1 had a mortality rate of 11.7%, group 2 had 7% mortality, and group 3 had 2.5% mortality. Group 1 had the highest incidence of postoperative complications. Surgical revascularization within 24 h of acute myocardial infarction was associated with significantly higher risks of mortality and morbidity than procedures performed after 72 h. PMID- 20304844 TI - Door-to-needle times in acute myocardial infarction. AB - Thrombolytic therapy is still the fastest and most accessible treatment for patients presenting with acute ST-elevation myocardial infarction. The time to treatment is a pivotal parameter in reperfusion. We examined the effects of implementing a better organized team approach to reduce door-to-needle times in patients with acute myocardial infarction. Fully trained emergency department personnel with special equipment facilitated direct communication between offsite cardiologists and pre-hospital emergency personnel, allowing for patient triage directly to the coronary care unit. Demographic, laboratory, and time interval data were prospectively collected and compared with data from previous years. From April to December 2007, 60 patients with acute ST-elevation myocardial infarction were triaged to the coronary care unit and enrolled in this study. Improvements were seen in mean door-to-needle time (reduced from 80 to 30 min during regular hours, and 85 to 33 min outside regular hours) compared with 2005 2007 data. A better organized team-based approach with specifically trained personnel and equipment for early evaluation and triage of patients with suspected myocardial infarction decreased intervention times, with the potential to be broadly applied in clinical practice and to improve patient survival. PMID- 20304845 TI - Autologous ring vs. flexible prosthetic ring for ischemic mitral regurgitation. AB - Ring annuloplasty is the most common strategy for correction of ischemic mitral regurgitation. When a commercial prosthesis is unavailable or too expensive, an autogenous annuloplasty ring can be handmade by the surgeon. The aim of this study was to compare short-term results of mitral valve repair with autologous annuloplasty rings and the SJM Tailor flexible prosthesis. Between March 2004 and April 2006, 100 patients undergoing coronary artery bypass grafting and mitral ring annuloplasty for ischemic regurgitation were randomly assigned to either type of prosthesis. Transesophageal and transthoracic echocardiography showed no significant differences between these techniques in terms of immediate success of the repair and its durability at 3, 6, and 9 months postoperatively. Autogenous rings are easy to make, cost-effective, and always available. Our short-term results suggest that they may be an acceptable alternative to a commercially produced prosthesis for patients with ischemic mitral regurgitation. PMID- 20304846 TI - Extracorporeal membrane oxygenation for children with fulminant myocarditis. AB - The purpose of this study was to evaluate the outcomes of children requiring extracorporeal membrane oxygenation for acute myocarditis. The hospital records of 8 patients who underwent membrane oxygenation for myocarditis from January 2002 to October 2008 were reviewed. Ages ranged from 3 to 12 years (median, 6 years). Duration of membrane oxygenation ranged from 89-502 h. Two patients who collapsed and required cardiac massage prior to membrane oxygenation did not survive. Five (62.5%) patients were discharged well, but one developed dilated cardiomyopathy and died 18 months later. One child had severe mitral regurgitation after weaning from membrane oxygenation, and underwent successful mitral valve repair. Another patient had no cardiac contractility for the initial 2 weeks, but regained good cardiac function after 21 days of support. She was weaned off membrane oxygenation and discharged home well. Complications included left hemiparesis in one patient and left hemothorax in 2. Recovery of cardiac function and a good outcome can be anticipated in children with acute myocarditis requiring membrane oxygenation. Initiation of membrane oxygenation before cardiovascular collapse increases the likelihood of survival. PMID- 20304847 TI - Bidirectional cavopulmonary shunt with additional pulmonary blood flow. AB - There are some controversies regarding the usefulness of leaving additional pulmonary blood flow when establishing a bidirectional cavopulmonary shunt. From April 2002 to September 2008, 13 patients (mean age, 24 +/- 16 months) underwent a bidirectional cavopulmonary shunt procedure with fine adjustment of additional pulmonary blood flow, as an intermediate step before the Fontan operation. There were no hospital deaths. Modified Blalock-Taussig shunts were left during the bidirectional cavopulmonary shunt operation in 7 patients, and pulmonary bands were tightened in 4. The main pulmonary artery with a previous pulmonary band was left open in one case. Oxygen saturation increased from 74.5% +/- 7.4% to 84.6% +/- 1.9% after the operation, cardiothoracic ratio decreased from 55.9% +/- 6.1% to 53.2% +/- 3.4%, Left ventricular end-diastolic pressure decreased from 11.0 +/ 2.6 to 7.8 +/- 3.0 mm Hg, and mean pulmonary arterial pressure from 14.7 +/- 7.5 to 10.2 +/- 3.1 mm Hg. Pulmonary artery index did not change significantly. In our experience, additional pulmonary blood flow with adjustment in each patient at the time of shunt construction was an excellent temporary palliation prior to the Fontan operation. PMID- 20304848 TI - Survival after surgery following chemotherapy for non-small-cell lung cancer. AB - A retrospective study was carried out on 74 patients with advanced non-small-cell lung cancer (52 in stage IIIA, 22 in stage IIIB) who received platinum-based induction chemotherapy in doublets and triplets, followed by tumor resection. Thirty-day postoperative mortality was 5.4% (4 patients); 5 patients in stage IIIB and 17 in stage IIIA did not respond, but the other 47 (63.5%) were downstaged to < IIIA (26 were downstaged to stage I, 20 to stage II, and 1 had complete remission). There was no change in T factor in 22 (30%) patients, nor in N factor in 21 (28%). The actuarial 5-year survival rate for patients in postoperative stages IIIA and IIIB was 0.496; survival was significantly longer in patients who responded to therapy. Parallel improvement in both T and N status predicted worse survival than a multistage regression in any single factor. N status was found to be a stronger survival indicator than T status. Cell type did not influence the response rate or outcome. Induction chemotherapy significantly improved survival in patients who responded, despite a poor prognosis. PMID- 20304849 TI - Oxygen pulse as a predictor of cardiopulmonary events in lung resection. AB - Traditional algorithms suggest a stepwise approach to the functional evaluation of candidates for lung resection. A cardiopulmonary exercise test is incorporated as a supplementary test for patients with borderline pulmonary predicted values, and sometimes as a first screening test for cardiac risk evaluation. To assess the predictive weight of exercise tests in noncardiac thoracic surgery, we retrospectively analyzed 99 patients (80 males) aged 67.8 +/-8.1 years who underwent lung resection after a cardiopulmonary exercise test. During basal spirometry, the mean predicted forced expiratory volume in the first second was 69.9% +/-18.6%, and predicted carbon monoxide diffusing capacity was 71.6% +/ 20.5%. Peak oxygen consumption was 11.1 +/-3.2 mL.kg(-1).min(-1), oxygen pulse was 9 +/-2.8 mL.beat(-1), and minute ventilation/CO(2) output was 45.2 +/- 7.7. Mean hospital stay was 10.4 days, and intensive care unit stay was 0.3 days. Postoperative complications occurred in 20 (20%) patients. On multivariate analysis, body mass index, a high level of exercise achieved during the cardiopulmonary exercise test, lower heart rate at peak exercise, and oxygen pulse correlated significantly with better postoperative outcome. Cardiopulmonary exercise tests are helpful for stratifying patients undergoing thoracic surgery. Perioperative complications seem to be strongly related to left ventricular function and physical performance. PMID- 20304850 TI - Mesothelial cells vs. skeletal myoblasts for myocardial infarction. AB - Cell transplantation for the regeneration of ischemic myocardium is limited by poor graft viability and low cell retention. Omental flaps in association with growth factors and cell sheets have recently been used to increase the vascularization of ischemic hearts. This experimental study was undertaken to evaluate the hemodynamic evolution and histological modifications of infarcted myocardium treated with mesothelial cells, and to compare the results with those of hearts treated with skeletal myoblasts. Myocardial infarction was created by surgical ligature of 2 coronary branches in 34 sheep; 6 died immediately due to ventricular fibrillation. Mesothelial cells were isolated from greater omentum, and myoblasts from skeletal muscle. After expanding the cells for 3 weeks, infarcted areas were treated with culture medium (control group), mesothelial cells, or myoblasts. After 3 months, echocardiographic studies showed significant limitation of ventricular dilatation and improved ejection fractions in both cell treated groups compared to the controls. In the mesothelial cell group, histological studies showed significantly more angiogenesis and arteriogenesis than in the control and skeletal myoblast groups. Mesothelial cells might be useful for biological revascularization in patients with ischemic heart disease. PMID- 20304851 TI - Clamp-and-sew technique for traumatic injuries of the aorta: 20-year experience. AB - Traumatic aortic injuries are associated with high morbidity and mortality, and the ideal operative approach for surgical management is unclear. We analyzed our results with the open clamp-and-sew technique over a 20-year period. Twenty patients with transected aorta were given interposition grafts; 19 of them had multisystem injuries. Mean aortic crossclamp time was 21.7 min (range, 12-30 min). Postoperative complications included pneumonia in 4 patients, acute renal failure in 1, recurrent laryngeal nerve injury in 2, chylothorax in 1, and sepsis of unknown etiology in one. There was no incidence of operation-related paraplegia. Although there was no 30-day mortality, one patient died after 90 days from diffuse axonal injuries to the brain. In experienced hands, the clamp and-sew technique is effective and safe for the management of traumatic aortic transection. PMID- 20304852 TI - Lower ministernotomy and fast tracking for atrial septal defect. AB - We report our experience with a 3-5-cm lower ministernotomy incision for closure of atrial septal defect in 53 patients. Fibrillatory arrest was used in 19 patients, and crossclamping with cardioplegia in 33. One patient had to be converted from fibrillatory arrest to crossclamping with cardioplegic arrest. The mean bypass time was 39.6 +/- 13.1 min, arrest time was 9.9 +/- 4.5 min, and crossclamp time was 20.7 +/- 8.69 min. All patients recovered without adverse events. They were fast tracked to recovery and extubated after 63.4 +/- 9.2 min. The mean intensive care unit stay was 1.07 +/- 0.33 days, and hospital stay was 3.07 +/- 0.38 days. The ministernotomy approach was used successfully in 51 patients; in the other 2, it had to be converted to a full sternotomy because of technical difficulties. Our experience confirms that this technique offers satisfactory cosmetic results, stable sternal reconstruction, good surgical exposure, minimal interference with respiratory mechanics, and minimal pain, allowing extubation in the operating room and a speedy recovery. PMID- 20304853 TI - Aprotinin confers neuroprotection by reducing apoptotic cell death. AB - Aprotinin has been used in pediatric cardiac surgery for its antiinflammatory and hemostatic benefits. We have reported that aprotinin has a direct cellular neuroprotective effect through reduction of excitotoxicity. The purpose of this study was to investigate whether aprotinin is neuroprotective against apoptotic cell death. Near-pure neuronal cultures containing <5% astrocytes were obtained from fetal mice. Serum deprivation was initiated at 7 days by transferring the cultures, which are dependent on serum for survival, into growth medium lacking serum for 24 h. Neuronal cell death was assessed by phase-contrast cell counting after staining with 0.4% trypan blue dye. Aprotinin at a clinically relevant concentration of 100 KIU.mL(-1) significantly reduced apoptotic neuronal cell death from 84.4% to 51.8%. This result suggests that aprotinin has the potential to reduce brain injury resulting from apoptotic cell death induced by an ischemic insult. Additional studies are needed to evaluate the potential of aprotinin to reduce neurological injury in patients at high risk of cerebral injury, including those undergoing circulatory arrest. PMID- 20304854 TI - Surgery for papillary fibroelastoma with uncommon location in left ventricle. AB - Cardiac papillary fibroelastoma is a rare tumor. Its location in the left ventricular wall is uncommon. A 59-year-old woman with 2 previous strokes presented with a tumor in the left ventricular apex. The patient underwent tumor resection through a left ventriculotomy. The histopathologic diagnosis was papillary fibroelastoma. PMID- 20304855 TI - Coronary artery graft dilatation aided by multidetector computed tomography. AB - Coronary angiography is the standard method of follow-up for patients with coronary artery bypass grafts, but it is an invasive and costly procedure that is not risk-free. Recently, 64-slice multidetector computed tomography has allowed reliable visualization of coronary artery grafts and their anastomotic status, with high spatial resolution. We describe a successful case of percutaneous coronary intervention for occluded coronary artery bypass grafts with the aid of multidetector computed tomography. PMID- 20304856 TI - Tender inflammatory infrarenal aortic aneurysm simulating acute rupture. AB - Even with multislice computed tomography, it may be difficult to differentiate contained ruptured or leaking atherosclerotic aneurysm from a tender inflammatory aneurysm. The decision for early intervention is based on clinical judgment. We describe successful open graft repair of a tender inflammatory infrarenal abdominal aortic aneurysm simulating acute rupture in a 63-year-old man. PMID- 20304857 TI - Repair of type A aortic dissection in nonagenarian. AB - Without emergency surgical management, acute type A aortic dissection carries a high risk of death. Controversy exists as to whether extreme age remains a contraindication to surgery. We describe successful repair of type A aortic dissection with ascending aortic graft replacement, aortic valve repair, hemiarch reconstruction, and ablation of atrial fibrillation in a 93-year-old man. PMID- 20304858 TI - Repair of ventricular septal perforation after inferior myocardial infarction. AB - Various techniques have been used for repair of ventricular septal perforation complicating inferior myocardial infarction, but no standard method has been established. An effective technique for closing ventricular septal perforation using double patches via a right atrial approach is described. In our experience, no residual shunt was observed after repair using this procedure. PMID- 20304859 TI - 3-dimensional structures to enhance cell therapy and engineer contractile tissue. AB - Experimental studies in animals and recent human clinical trials have revealed the current limitations of cellular transplantation, which include poor cell survival, lack of cell engraftment, and poor differentiation. Evidence in animals suggests that use of a 3-dimensional scaffold may enhance cell therapy and engineer myocardial tissue by improving initial cell retention, survival, differentiation, and integration. Several scaffolds of synthetic or natural origin are under development. Until now, contractility has been demonstrated in vitro only in biological scaffolds prepared from decellularized organs or tissue, or in collagenic porous scaffold obtained by crosslinking collagen fibers. While contractility of a cellularized collagen construct is poor, it can be greatly enhanced by tumor basement membrane extract. Recent advances in biochemistry have shown improved cell-matrix interactions by coupling adhesion molecules to achieve an efficient and safe bioartificial myocardium with no tumoral component. Fixation of adhesion molecules may also be a way to enhance cell homing and/or differentiation to increase local angiogenesis. Whatever the clinically successful combination ultimately proves to be, it is likely that cell therapy will require providing a supportive biochemical, physical, and spatial environment that will allow the cells to optimally differentiate and integrate within the target myocardial tissue. PMID- 20304860 TI - Unruptured noncoronary sinus of valsalva aneurysm. PMID- 20304861 TI - "Hotshot" into the heart. PMID- 20304862 TI - Mitral insufficiency 30 years after resection of subvalvular aortic stenosis. PMID- 20304863 TI - Partial anomalous pulmonary venous return. PMID- 20304865 TI - Association between carotid atherosclerosis and metabolic syndrome: results from the ISMIR study. AB - The metabolic syndrome (MetS) has previously been associated with an early marker of atherosclerosis, the carotid intima-media thickness (IMT). From the ISMIR (Ispessimento Medio Intimale e Rischio cardiovascolare [media-intima thickness and cardiovascular risk]) study population of 479 asymptomatic participants, we identified 80 participants with MetS. Carotid IMT and plaques were evaluated by ultrasonography. Blood samples were obtained from all participants. Participants with MetS had a significantly higher prevalence of a carotid IMT > 0.80 mm (P = .004) and of carotid plaques (P < .001) as compared with participants without MetS. Carotid IMT was significantly correlated with fasting triglycerides and fibrinogen levels both in participants with MetS and in those without MetS (all P < .01). In contrast, IMT correlated with fasting plasma glucose, serum creatinine, and uric acid levels only in participants without MetS. Our study confirms the association between MetS and carotid atherosclerosis. In MetS, a significant correlation between carotid IMT and triglycerides and fibrinogen levels was found. PMID- 20304864 TI - Differential activation of frontoparietal attention networks by social and symbolic spatial cues. AB - Perception of both gaze-direction and symbolic directional cues (e.g. arrows) orient an observer's attention toward the indicated location. It is unclear, however, whether these similar behavioral effects are examples of the same attentional phenomenon and, therefore, subserved by the same neural substrate. It has been proposed that gaze, given its evolutionary significance, constitutes a 'special' category of spatial cue. As such, it is predicted that the neural systems supporting spatial reorienting will be different for gaze than for non biological symbols. We tested this prediction using functional magnetic resonance imaging to measure the brain's response during target localization in which laterally presented targets were preceded by uninformative gaze or arrow cues. Reaction times were faster during valid than invalid trials for both arrow and gaze cues. However, differential patterns of activity were evoked in the brain. Trials including invalid rather than valid arrow cues resulted in a stronger hemodynamic response in the ventral attention network. No such difference was seen during trials including valid and invalid gaze cues. This differential engagement of the ventral reorienting network is consistent with the notion that the facilitation of target detection by gaze cues and arrow cues is subserved by different neural substrates. PMID- 20304866 TI - Involvement of ERK1/2 kinase in insulin-and thrombin-stimulated vascular smooth muscle cell proliferation. AB - It is well recognized that the proliferation of vascular smooth muscle cells (VSMCs) is a key event in the pathogenesis of various vascular diseases, including atherosclerosis and hypertension. We have previously shown that among extracellular signal-regulated protein kinases (ERKs), the 42- and 44-kDa isoforms (ERK1/2) participate in the cellular mitogenic machinery triggered by several VSMCs activators, including insulin (INS) and thrombin (Thr). However, understanding of the intracellular signal transduction pathways involved is incomplete. This review considers the recent findings in INS and Thr signaling mechanisms that modulate the proliferation of VSMCs with particular emphasis on the ERK1/2 signaling pathway, an important mediator of VSMCs hypertrophy and vascular disease. Moreover, because the ERK1/2 pathway have been acknowledged as an important mediator of VSMCs hypertrophy, ERK1/2 is identified as a key target for novel therapeutic interventions to minimize irreversible tissue damage associated with hypertension and atherosclerosis. PMID- 20304867 TI - Impact of fibrinogen levels on angiographic progression and 12-year survival in the armed forces regression study. AB - We assessed the role of fibrinogen levels on angiographic progression and long term survival among 111 patients with coronary disease enrolled in the Armed Forces Regression Study (AFREGS). Baseline fibrinogen levels and quantitative coronary angiography were performed initially and at 30 months. Progression or nonregression of coronary disease was more prevalent in patients with high fibrinogen than patients with normal fibrinogen (66.1% vs 45.5%; P = .022). Twelve-year cardiovascular (CV) mortality was substantially higher if fibrinogen was elevated (17.9% vs 3.6%, P = .016). Among patients with elevated fibrinogen and angiographic progression or nonregression, there were 10 deaths and all were CV. Elevated levels of fibrinogen predict the angiographic progression of existing coronary disease and likelihood of CV death. Among patients with elevated levels of fibrinogen, angiographic progression identifies a significantly increased likelihood of a fatal CV event. PMID- 20304868 TI - Levels of sCD40 ligand in chronic and acute coronary syndromes and its relation to angiographic extent of coronary arterial narrowing. AB - We determined the serum levels of soluble CD40 ligand (sCD40L) in patients with chronic coronary artery disease (CAD) and acute coronary syndrome (ACS). Patients with unstable angina (UA) and myocardial infarction (MI) showed significantly higher levels (P < .001) of sCD40L compared with patients with stable angina (SA) and controls; particularly, high levels occurred in patients with UA (UA: 9.23 +/ 2.92, MI: 7.38 +/- 1.05, SA: 4.42 +/- 1.08; control: 4.01 +/- 0.87 ng/mL). There was no significant difference in sCD40L levels between patients with UA and MI or between patients with SA and controls. Levels of sCD40L did not show any significant correlation with peak creatine kinase (CK), CK-MB isoenzyme activity in patients with MI, troponin T serum levels in patients with UA or with culprit vessel (CV) complexity score (CVCS), type of CV lesion, or vessel score in patients with UA or MI. These results suggest that CD40L plays a pathogenic role in triggering ACS. PMID- 20304870 TI - Caring to the end? PMID- 20304869 TI - Sedentary behaviours and socio-economic status in Spanish adolescents: the AVENA study. AB - BACKGROUND: This study aimed to describe the influence of socio-economic status (SES) on the prevalence sedentary behaviours among Spanish adolescents. METHODS: Cross-sectional data from Spanish adolescents from the Alimentacion y Valoracion del Estado Nutricional de los Adolescentes (AVENA) Study (2002). A national representative sample of 1776 adolescents aged 13-18.5 years provided information about time spent watching television (TV), playing with computer or videogames and studying. Parental education and occupation were assessed as SES. Participants were categorized by gender, age, parental education and occupation. Logistic regression models were used. RESULTS: No gender differences were found for TV viewing. For computer and videogames use (weekdays), more boys played >3 h/day (P < 0.001), whereas a higher percentage of girls reported studying >3 h/day (P < 0.001). Among boys, parental education and occupation were inversely associated with TV viewing, parental occupation directly associated with study and maternal education inversely with computer and videogames use during weekdays (all P < 0.05). For girls, parental occupation was inversely associated with TV viewing. CONCLUSION: Spanish adolescents presented different sedentary patterns according to age, gender and SES. Boys reported more time engaged in electronic games, whereas girls reported more time studying. Parental occupation had more influence than parental education on the time spent in sedentary behaviours. PMID- 20304871 TI - The College of Paramedics (British Paramedic Association) position paper regarding the Joint Royal Colleges Ambulance Liaison Committee recommendations on paramedic intubation. PMID- 20304872 TI - Joint Royal College Ambulance Liaison Committee Airway Working Group commentary. PMID- 20304873 TI - Prehospital airway management. PMID- 20304874 TI - The implications of the NICE guidelines on neurosurgical management for all severe head injuries: systematic review. AB - Head injury is an important cause of death among young adults in the UK, and a significant burden on NHS resources. However, management is inconsistent, governed largely by local resources. The latest version of the NICE head injury guidelines suggests that more patients with traumatic brain injury should be transferred to receive specialist care. However, this raises issues about the capacity of regional neurosurgical units, particularly to accommodate patients who do not require surgical intervention. OBJECTIVES: To critically evaluate the basis of the NICE recommendations about transfer for neurosurgical care, and examine the configuration of specialist services to assess the implications of increasing the existing number of transfers. METHODS: A systematic literature review was conducted of articles discussing the provision of emergency neurosurgical care for adult head injuries in the UK. RESULTS: Fifty-eight papers met the criteria for inclusion in the literature review, including seven papers cited in the NICE guidance. Fifty-one papers related to neurosurgical care, including papers on bed occupancy, transfer times and transfer policies. CONCLUSIONS: The evidence NICE cited is of variable quality. Much of the research was conducted outside the UK, which raises questions about its relevance to the NHS. Care of traumatic brain injuries in the UK is already hampered by the inadequate capacity of regional neurosurgical units to meet demand, and transferring more patients would be likely to exacerbate this. Increasing the number of transfers could also worsen inequalities of access for other groups, such as elective patients, particularly in areas where facilities are most stretched. PMID- 20304876 TI - Hostel emergency medicine in Iran. PMID- 20304877 TI - Urgent care and the patient. PMID- 20304878 TI - Alternative services to deliver urgent care in the community. PMID- 20304879 TI - Access to urgent health care. PMID- 20304880 TI - Secondary care and changing the face of emergency care. PMID- 20304881 TI - Provision of trauma teams in Scotland: a national survey. AB - BACKGROUND AND AIMS: Trauma is still the leading cause of mortality in the first four decades of life. Despite numerous reports on how trauma care could be improved in the UK, treatment has been shown to be inconsistent and of poor quality. Trauma teams have been shown to have a positive effect on outcome. A study was undertaken to determine the prevalence of trauma teams in Scotland. METHODS: A telephone survey was performed of 24 hospitals with emergency departments in which the senior clinician was interviewed regarding the provision of trauma teams. RESULTS: Five (21%) of the hospitals questioned had trauma teams. The most common reasons for not having one were no problem with the current system in eight cases (44%) and an inability to include sufficiently senior staff on the team in six cases (24%). CONCLUSIONS: There are few trauma teams in Scottish acute hospitals. There was little enthusiasm for introducing them for a variety of reasons. Local evidence of benefit is probably needed before their adoption becomes widespread. PMID- 20304882 TI - A late complication of a traumatic flail segment: colonic herniation. PMID- 20304883 TI - Point of care troponin decreases time in the emergency department for patients with possible acute coronary syndrome: a randomised controlled trial. AB - OBJECTIVE: To determine the effect of cardiac troponin I testing with a point-of care (POC) device versus central laboratory on length of stay (LOS) in emergency department (ED) patients presenting with possible acute coronary syndromes (ACS). METHODS: A 12-week randomised controlled trial at two metropolitan ED in eastern Australia with a combined annual census of 80,000. Participants were all patients presenting with possible ACS. Exclusions were a diagnosis of ACS before arrival, ST elevation and failure to wait for complete assessment. Randomisation was by week when POC was made available. Primary outcome was LOS from patient arrival to physical departure from the ED. The proportion of patients meeting a government target of less than 8 h stay was compared. Analysis was by intention to treat. RESULTS: Despite underutilisation of POC, LOS was shorter during weeks when it was available. The time savings translates into approximately 48 minutes (95% CI 12 to 84) per average LOS of almost 7 h, which did not reach statistical significance (p=0.063), or an absolute increase of 10% (95% CI 4.3 to 16.6) in the number of people discharged from the ED within the target LOS of less than 8 h, which did reach significance (p=0.007). These savings were more pronounced in the setting without 24 h central laboratory availability. CONCLUSIONS: POC testing for troponin in the ED tended to reduce the LOS for possible ACS patients. The degree of this benefit is likely to be markedly dependent on its acceptance and uptake by attending personnel, and on the ED setting in which it is used. PMID- 20304884 TI - Emergency retinal pallor. PMID- 20304885 TI - Alcohol intoxication at a university hospital acute medicine unit--with special consideration of young adults: an 8-year observational study from Switzerland. AB - BACKGROUND: Many media reports suggest an increase in alcohol intoxication, particularly among young people. Indeed, several surveys on young people have confirmed this fact. These were based on self-declaration of alcohol consumption. However, there are few clinical data that show an increase in alcohol intoxication in hospitals. The aim of this study was to evaluate the number of alcohol intoxications in relation to the total number of patients and to look for a statistical trend. METHODS: Using their electronic database, the authors identified all patients with alcohol intoxication who were treated in the acute medical wing of our ED in the years 2000-2007. In the group aged 16-25 years, the authors searched for combined intoxication. RESULTS: The authors found a significant increase in alcohol intoxication in all age groups and also in young people aged below 25 years. There were more intoxicated males than females (male to female ratio 1.5:1). The age distribution of our intoxicated patients showed a peak at 35-45 years of age and repeated admissions were frequent in this age class. Drugs consumed together with alcohol in the age group 16-25 were mostly cannabis and cocaine. CONCLUSION: Episodic drinking is not only a problem in the 16-25 age group, it also concerns men of 35-45 years. This is a major public health problem in industrialised countries. Intoxicated patients are at acute risk of injuries and violence following alcohol abuse. Preventive measures should not only be limited to younger adults. PMID- 20304886 TI - What factors are associated with repeated domestic assault in patients attending an emergency department? A cohort study. AB - OBJECTIVE: To identify what clinical variables are associated with repeat attendances at the emergency department (ED) in patients who have experienced domestic assault. METHODS: A medical records-based cohort study was conducted in a single ED in Cambridge, UK. PARTICIPANTS: 294 adult patients with disclosed domestic assault presenting between 2001 and 2004 were followed up by examining their medical records until 2004. MAIN OUTCOME MEASURES: Re-presentation at the ED with disclosed domestic assault. RESULTS: 45 patients re-presented at the ED with further domestic assault. Repeated assault was more likely in patients in whom no clear diagnosis was made (odds ratio (OR) 4.6 95%, CI 1.4 to 14.5; p<0.001), who had head injuries (OR 4.08, 95% CI 1.94 to 8.59; p<0.001), injuries to the upper limb (OR 1.94, 95% CI 1.01 to 3.73; p=0.05), or who had a psychiatric diagnosis (OR 3.43, 95% CI 1.34 to 8.76; p=0.1). CONCLUSIONS: There are readily measurable clinical features that are associated with repeat ED attendance as a result of domestic assault. PMID- 20304888 TI - Things that go bump ... bump ... bump: an analysis of injuries from falling down stairs in children based at Sheffield Children's Hospital. AB - BACKGROUND: Falls down stairs are a common presentation to the paediatric emergency department. The pattern of injury associated with this mechanism of injury has not been described for the UK population. A retrospective analysis of attendances to the Emergency Department of Sheffield Children's Hospital was carried out. RESULTS: Overall 90% (216/239) of patients sustained one or more injuries; 69% (165/239) sustained minor head and facial injuries; 12% (29/239) sustained minor soft tissue injuries of other regions; 10% (23/239) had limb fractures, of which 60% (14/23) were of the upper limb (nine clavicle fractures, one supracondylar fracture of the elbow and four wrist fractures) and 40% (9/23) were of the lower limb (four femoral fractures and five tibial fractures). Two per cent (5/239) had skull fractures (all were in the group of children dropped while being carried on the stairs). Injuries to more than one body part occurred in only 3% (8/239) of cases. DISCUSSION: The results suggest that children who fall down the stairs are mainly toddlers and in general sustain only minor injuries, the commonest being a minor head injury. Severe truncal and extremity injuries or injuries involving multiple body regions should provoke further questioning looking for evidence of non-accidental injury. There is no correlation between the number of stairs fallen down and the likelihood or severity of injury. CONCLUSION: Infants who fall down stairs with their carer or are dropped while being carried down stairs require an especially close evaluation. PMID- 20304889 TI - Elevated serum S100B levels in acute spinal fracture without head injury. AB - BACKGROUND: S100B is a biomarker that reflects injury to the central nervous system. As the spine is an integral part of the spinal cord, a study was undertaken to investigate whether serum S100B levels are associated with acute spinal fracture without head injury. METHODS: The study population consisted of 32 consecutive patients aged > or = 18 years in whom the emergency physicians suspected spinal fractures. All the patients underwent CT scans to establish the diagnosis of spinal fracture. MRI was then performed on all the patients to determine the presence of spinal cord injury. RESULTS: Serum S100B levels were higher in the spinal fracture group than in the non-spinal fracture group, and 19 of the 20 patients in the spinal fracture group (95%) had an S100B level >0.12 microg/l, whereas all 12 of the non-spinal fracture group had an S100B level < or = 0.12 microg/l. The S100B level in patients with epidural encroachment of the spinal cord was significantly higher (0.22-4.58 microg/l; mean 2.45 microg/l; 95% CI 0.95 to 3.94) than in those without epidural encroachment (0.114-2.87 microg/l; mean 0.80 microg/l; 95% CI 0.24 to 1.37) (p=0.037). Plain radiography revealed no definite abnormal findings in half of the patients with spinal fracture. CONCLUSIONS: Serum S100B levels are raised in all patients with acute spinal fracture without head injury. Spinal fracture may therefore be one of the extracerebral sources of S100B. Serum S100B levels may be an effective tool for excluding subtle spinal fractures with no clear radiographic findings. PMID- 20304890 TI - Tuberculous tension pneumothorax. PMID- 20304891 TI - To ED or not to ED: NHS 24 referrals to the emergency department. AB - INTRODUCTION: This study aimed to compare the opinions of consultants in emergency medicine and general practitioners (GPs) on the appropriateness of NHS 24 referrals to the emergency department (ED). METHODS: 170 NHS 24 referrals to the ED were reviewed by six GPs and six emergency consultants who were asked their opinion as to which out-of-hours service would be most appropriate for the patient. Modal responses from both groups were calculated for each referral. Consensus within groups and levels of agreement were calculated. RESULTS: Modal responses agreed with an ED disposal in 59.2% of cases in the emergency consultant group with a 90% consensus rate. The GP group agreed with an ED disposal in only 47% of cases with a 75.9% consensus rate. A primary care referral response was the mode in 20.8% of the emergency consultant group compared with 35.7% in the GP group. Consensus was reached in 76.3% of the emergency consultant responses and 81.7% of GP responses. The difference in opinion between the two study groups was statistically significant. CONCLUSIONS: GPs and consultants in emergency medicine both believe a high proportion of NHS 24 referrals to the ED should be handled by primary care services. This would suggest that, compared with previous out-of-hours practice, NHS 24 favours an ED outcome. The results indicate a large proportion of primary care patients are being handled inappropriately and uneconomically in the ED setting. There is a need for ongoing improvement of the telephone triage service provided by NHS 24. PMID- 20304892 TI - Temporal and spatial characteristics and treatment strategies of traumatic brain injury in Wenchuan earthquake. AB - OBJECTIVE: To analyse the temporal and spatial characteristics of traumatic brain injury and the distribution of combined injuries in the Wenchuan earthquake, and describe the treatment opportunities and preferences for therapy. METHODS: The diagnosis and treatment of 92 patients with traumatic brain injury who survived the massive earthquake (magnitude 8) in Wenchuan, Sichuan Province, on 12 May 2008 were systematically analysed. RESULTS: The patients all came from the plains northwest of Chengdu city. Seventy-six patients were admitted during the early stage (within 12 h) after the earthquake. Ten patients underwent surgery and three patients died. CONCLUSION: Patients with traumatic brain injury during the early period accounted for a large proportion of the patients wounded in the Wenchuan earthquake, and their conditions changed quickly. The patients all came from the plain area which has convenient transportation. After admission, providing first-aid early had a significant effect on increasing the success of treatment for these patients. PMID- 20304893 TI - Spontaneous pneumocephalus. PMID- 20304894 TI - Surveying young patients. AB - The East of England Ambulance Service NHS Trust (the Trust) was keen to engage young patients and to encourage them to give feedback about the service they had received. The standard Trust satisfaction survey was modified for use with young patients, and this had the effect of increasing the response rate from this patient group by 8%, and increasing the percentage of young patients aged 5-10 years completing the survey themselves by 29%. The vast majority of parents/guardians were happy for the Trust to survey their child, but the age of the child affected to whom they would like the survey sent. The Trust subsequently altered patient survey practice to write to parents/guardians of patients aged <12 years and directly to all patients aged > or = 12 years. PMID- 20304895 TI - Sonographic diagnosis of epiglottal enlargement. AB - The case is presented of epiglottal and pre-epiglottal oedema secondary to infection of the pharyngolaryngeal area. The purpose of this report was to assess the utility of ultrasonography to image epiglottal and pre-epiglottal oedema. Bedside emergency department ultrasonography could be a valuable tool to detect pathological enlargement of the epiglottis. Ultrasonography may be used in unstable patients for diagnosing epiglottitis because it is cheap, rapid, non invasive and does not aggravate the patient's symptoms. PMID- 20304896 TI - Unusual cause of acute upper airway obstruction. PMID- 20304897 TI - A critical reassessment of ambulance service airway management in prehospital care: Joint Royal Colleges Ambulance Liaison Committee Airway Working Group, June 2008. AB - Paramedic tracheal intubation has been practised in the UK for more than 20 years and is currently a core skill for paramedics. Growing evidence suggests that tracheal intubation is not the optimal method of airway management by paramedics and may be detrimental to patient outcomes. There is also evidence that the current initial training of 25 intubations performed in-hospital is inadequate, and that the lack of ongoing intubation practice may compound this further. Supraglottic airway devices (eg, laryngeal mask airway), which were not available when extended training and paramedic intubation was first introduced, are now in use in many ambulance services and are a suitable alternative prehospital airway device for paramedics. PMID- 20304898 TI - Bilateral chronic subdural haematoma misdiagnosed as neuroleptic malignant syndrome. PMID- 20304900 TI - A congenital abnormality masquerading as encephalitis in an 11-year-old girl. AB - Craniopharyngiomas are reported to be the commonest non-glial tumours of childhood. The classic presentation is typically progressive, commonly manifested as visual field defects, growth abnormalities and/or endocrine disturbance. We report a case of an 11-year-old girl presenting in acute confusional state, with few historical factors suggestive of an intracranial mass lesion and no objective localising signs on examination. Although initially treated as encephalitis, neuroimaging revealed a large craniopharyngioma with acute hydrocephalus and bilateral frontal lobe compression. She was transferred immediately to the local neurosurgical unit and underwent reservoir drainage of the cystic tumour within 24 h. This resulted in immediate symptomatic resolution. This case highlights the importance of early cerebral imaging in the paediatric patient with diagnostic uncertainty and suggests a high index of suspicion for space-occupying lesions in children, despite perceived duration of symptoms. PMID- 20304901 TI - An unusual presentation of congenital central hypoventilation syndrome (Ondine's Curse). AB - Congenital central hypoventilation syndrome is a rare illness, which classically presents in the neonatal period; newborns present with shallow breathing and cyanosis, without a physiological rise in breathing rate. Incidence has been estimated from 1 in 10,000 to 1 in 200,000 live births. This case report describes the case of a young man who was asymptomatic until his presentation in acute respiratory failure at the age of 36 years. This case is reported to highlight the importance of considering this treatable illness as a potential cause of collapse and respiratory failure in adults presenting to emergency departments. PMID- 20304902 TI - Asymptomatic left-sided pericardial cyst. PMID- 20304903 TI - Spotting the complex tachycardia. AB - A young man presented to the emergency department with ventricular tachyarrhythmia later attributed to varicella zoster myocarditis. Myocarditis has an unpredictable clinical sequelae, making it a difficult condition to diagnose and manage in the emergency setting. The inconsistent clinical presentations, risks and management are demonstrated through a review of the literature. PMID- 20304904 TI - Image on spontaneous pneumomediastinum presenting as sore throat. PMID- 20304905 TI - Towards evidence based emergency medicine: best BETs from the Manchester Royal Infirmary. BET 1: Adding clopidogrel to standard treatment for acute myocardial infarction. PMID- 20304907 TI - Towards evidence based emergency medicine: best BETs from the Manchester Royal Infirmary. BET 2: Rapid influenza testing of febrile children in the emergency department. PMID- 20304908 TI - Towards evidence based emergency medicine: best BETs from the Manchester Royal Infirmary. BET 3: Use of thrombolysis in acute ischaemic stroke. PMID- 20304909 TI - Boosting interface medicine. PMID- 20304910 TI - Patient satisfaction and healthcare providers. PMID- 20304912 TI - Point mutation of a plastidic invertase inhibits development of the photosynthetic apparatus and enhances nitrate assimilation in sugar-treated Arabidopsis seedlings. AB - Because the photosynthetic apparatus contains a massive amount of nitrogen in plants, the regulation of its development by sugar signals is important to the maintenance of the carbon-nitrogen balance. In this study we isolated an Arabidopsis mutant (sicy-192) whose cotyledon greening was inhibited by treatments with sugars such as sucrose, glucose, and fructose. In the mutant, the gene encoding plastidic alkaline/neutral invertase (INV-E) was point-mutated at codon 294, with Tyr substituted for Cys (C294Y). Interestingly, the greening of cotyledons in the knock-out INV-E lines was not inhibited by treatment with the sugars. In addition, the knock-out INV-E lines expressing an INV-E:C294Y or INV E:C294A gene had the same phenotype as sicy-192 mutants, whereas the lines expressing a wild-type INV-E gene had the same phenotype as wild-type plants. A recombinant INV-E:C294Y protein had the same enzymatic activity as a recombinant INV-E protein, suggesting that the Cys-294 residue of INV-E is important for its functions in the chloroplasts. On treatment with sucrose, the expression of photosynthesis-related genes was weaker in seedlings of mutant plants than wild type seedlings, whereas the activity of nitrate reductase was stronger in the mutant plants than wild-type plants. These findings suggest that Cys-294 of INV-E is associated with the development of the photosynthetic apparatus and the assimilation of nitrogen in Arabidopsis seedlings to control the ratio of sucrose content to hexose content. PMID- 20304913 TI - Metabolic and transcriptional responses of glycerolipid pathways to a perturbation of glycerol 3-phosphate metabolism in Arabidopsis. AB - Glycerolipid synthesis in plants involves two major metabolic pathways compartmentalized in the chloroplasts and cytosol, respectively. Although these two parallel pathways are regulated with considerable flexibility, the factors mediating this process remain unclear. To investigate the influence of glycerol 3 phosphate (Gly-3-P) on the interactions of the glycerolipid pathways, we generated transgenic Arabidopsis lines with a feedback-resistant Gly-3-P dehydrogenase gene (gpsA(FR)) from Escherichia coli. gpsA(FR) was detected in the cytosol, but augmented Gly-3-P levels were observed in the cytosol as well as in chloroplasts. Glycerolipid composition and fatty acid positional distribution analyses revealed an altered fatty acid flux that affected not only the molar ratios of glycerolipid species but also their fatty acid composition. To decipher this complex pathway, a transgenic line was subjected to lipidomic analysis and a global gene-expression survey. The results revealed that changes in Gly-3-P metabolism caused altered expression of a broad array of genes. When viewed from the perspective of glycerolipid metabolism, coherent networks emerged, revealing that many enzymatic components of the glycerolipid pathways operate in a modular manner under the influence of Gly-3-P. Transcript levels of the enzymes involved in the prokaryotic pathway were mostly induced, whereas genes of the eukaryotic pathway enzymes were largely suppressed. Hence, the gene-expression changes were consistent with the detected biochemical phenotype. Our results suggest that Gly 3-P modulates the balance of the two glycerolipid pathways in Arabidopsis by influencing both metabolic flux and gene transcription. PMID- 20304914 TI - Transcription-dependent activation of ataxia telangiectasia mutated prevents DNA dependent protein kinase-mediated cell death in response to topoisomerase I poison. AB - Camptothecin (CPT) is a topoisomerase I inhibitor, derivatives of which are being used for cancer chemotherapy. CPT-induced DNA double-strand breaks (DSBs) are considered a major cause of its tumoricidal activity, and it has been shown that CPT induces DNA damage signaling through the phosphatidylinositol 3-kinase related kinases, including ATM (ataxia telangiectasia mutated), ATR (ATM and Rad3 related), and DNA-PK (DNA-dependent protein kinase). In addition, CPT causes DNA strand breaks mediated by transcription, although the downstream signaling events are less well characterized. In this study, we show that CPT-induced activation of ATM requires transcription. Mechanistically, transcription inhibition suppressed CPT-dependent activation of ATM and blocked recruitment of the DNA damage mediator p53-binding protein 1 (53BP1) to DNA damage sites, whereas ATM inhibition abrogated CPT-induced G(1)/S and S phase checkpoints. Functional inactivation of ATM resulted in DNA replication-dependent hyperactivation of DNA PK in CPT-treated cells and dramatic CPT hypersensitivity. On the other hand, simultaneous inhibition of ATM and DNA-PK partially restored CPT resistance, suggesting that activation of DNA-PK is proapoptotic in the absence of ATM. Correspondingly, comet assay and cell cycle synchronization experiments suggested that transcription collapse occurring as the result of CPT treatment are converted to frank double-strand breaks when ATM-deficient cells bypass the G(1)/S checkpoint. Thus, ATM suppresses DNA-PK-dependent cell death in response to topoisomerase poisons, a finding with potential clinical implications. PMID- 20304915 TI - Mammalian prions generated from bacterially expressed prion protein in the absence of any mammalian cofactors. AB - Transmissible spongiform encephalopathies (TSEs) are a group of neurodegenerative diseases that are associated with the conformational conversion of a normal prion protein, PrP(C), to a misfolded aggregated form, PrP(Sc). The protein-only hypothesis asserts that PrP(Sc) itself represents the infectious TSE agent. Although this model is supported by rapidly growing experimental data, unequivocal proof has been elusive. The protein misfolding cyclic amplification reactions have been recently shown to propagate prions using brain-derived or recombinant prion protein, but only in the presence of additional cofactors such as nucleic acids and lipids. Here, using a protein misfolding cyclic amplification variation, we show that prions causing transmissible spongiform encephalopathy in wild-type hamsters can be generated solely from highly purified, bacterially expressed recombinant hamster prion protein without any mammalian or synthetic cofactors (other than buffer salts and detergent). These findings provide strong support for the protein-only hypothesis of TSE diseases, as well as argue that cofactors such as nucleic acids, other polyanions, or lipids are non-obligatory for prion protein conversion to the infectious form. PMID- 20304916 TI - Distribution and function of macrophage galactose-type C-type lectin 2 (MGL2/CD301b): efficient uptake and presentation of glycosylated antigens by dendritic cells. AB - Dendritic cells (DCs) express cell surface lectins that are potentially involved in the recognition, uptake, and presentation of glycosylated foreign substances. A unique calcium-type (C-type) lectin, the macrophage galactose (Gal)-type C-type lectin (MGL/CD301) expressed on DCs, is thought to participate in the recognition of molecules from both altered self and pathogens due to its monosaccharide specificity for Gal and N-acetylgalactosamine (GalNAc). Although mice have two MGL genes, Mgl1 and Mgl2, their distinct roles have not been previously explored. The present report characterizes the properties of MGL2 by examining its distribution and its role in antigen presentation by DCs. We generated an MGL2 specific monoclonal antibody and examined MGL2 expression in tissues by immunohistochemistry and in isolated cells by flow cytometry. The cells reactive with this antibody were shown to be a portion of MGL1-expressing cells, mostly conventional DCs. Internalization of soluble polyacrylamide polymers (PAA) with alpha-GalNAc residues (GalNAc-PAA) by bone marrow-derived DCs (BM-DCs) was mediated by MGL2, as revealed by a comparison of Mgl1(-/-) and Mgl2(-/-) BM-DCs with wild-type BM-DCs. Biotinylated GalNAc-PAA conjugated to streptavidin (SAv) was more efficiently presented to SAv-primed T cells by BM-DCs than beta-N acetylglucosamine-PAA conjugated to SAv or SAv alone as shown by thymidine uptake and cytokine production. This is the first report that demonstrates the involvement of GalNAc residues in antigen uptake and presentation by DCs that lead to CD4(+) T cell activation. PMID- 20304918 TI - TAX1BP1 and A20 inhibit antiviral signaling by targeting TBK1-IKKi kinases. AB - Induction of type I interferons by the transcription factor IRF3 is essential in the initiation of antiviral innate immunity. Activation of IRF3 requires C terminal phosphorylation by the upstream kinases TBK1-IKKi, where IRF3 phosphorylation promotes dimerization, and subsequent nuclear translocation to the IFNbeta promoter. Recent studies have described the ubiquitin-editing enzyme A20 as a negative regulator of IRF3 signaling by associating with TBK1-IKKi; however, the regulatory mechanism of A20 inhibition remains unclear. Here we describe the adaptor protein, TAX1BP1, as a key regulator of A20 function in terminating signaling to IRF3. Murine embryonic fibroblasts (MEFs) deficient in TAX1BP1 displayed increased amounts of IFNbeta production upon viral challenge compared with WT MEFs. TAX1BP1 inhibited virus-mediated activation of IRF3 at the level of TBK1-IKKi. TAX1BP1 and A20 blocked antiviral signaling by disrupting Lys(63)-linked polyubiquitination of TBK1-IKKi independently of the A20 deubiquitination domain. Furthermore, TAX1BP1 was required for A20 effector function because A20 was defective for the targeting and inactivation of TBK1 and IKKi in Tax1bp1(-)(/)(-) MEFs. Additionally, we found the E3 ubiquitin ligase TRAF3 to play a critical role in promoting TBK1-IKKi ubiquitination. Collectively, our results demonstrate TBK1-IKKi to be novel substrates for A20 and further identify a novel mechanism whereby A20 and TAX1BP1 restrict antiviral signaling by disrupting a TRAF3-TBK1-IKKi signaling complex. PMID- 20304917 TI - Structural characterization of apical membrane antigen 1 (AMA1) from Toxoplasma gondii. AB - Apical membrane antigen 1 (AMA1) is an essential component of the moving junction complex used by Apicomplexan parasites to invade host cells. We report the 2.0 A resolution x-ray crystal structure of the full ectodomain (domains I, II, and III) of AMA1 from the pervasive protozoan parasite Toxoplasma gondii. The structure of T. gondii AMA1 (TgAMA1) is the most complete of any AMA1 structure to date, with more than 97.5% of the ectodomain unambiguously modeled. Comparative sequence analysis reveals discrete segments of divergence in TgAMA1 that map to areas of established functional importance in AMA1 from Plasmodium vivax (PvAMA1) and Plasmodium falciparum (PfAMA1). Inspection of the TgAMA1 structure reveals a network of apical surface loops, reorganized in both size and chemistry relative to PvAMA1/PfAMA1, that appear to serve as structural filters restricting access to a central hydrophobic groove. The terminal portion of this groove is formed by an extended loop from DII that is 14 residues shorter in TgAMA1. A pair of tryptophan residues (Trp(353) and Trp(354)) anchor the DII loop in the hydrophobic groove and frame a conserved tyrosine (Tyr(230)), forming a contiguous surface that may be critical for moving junction assembly. The minimalist DIII structure folds into a cystine knot that probably stabilizes and orients the bulk of the ectodmain without providing excess surface area to which invasion-inhibitory antibodies can be generated. The detailed structural characterization of TgAMA1 provides valuable insight into the mechanism of host cell invasion by T. gondii. PMID- 20304919 TI - Histidine residue mediates radical-induced hinge cleavage of human IgG1. AB - Hydroxyl radicals induce hinge cleavage in a human IgG1 molecule via initial radical formation at the first hinge Cys(231) followed by electron transfer to the upper hinge residues. To enable engineering of a stable monoclonal antibody hinge, we investigated the role of the hinge His(229) residue using structure modeling and site-directed mutagenesis. Direct involvement of His(229) in the reaction mechanism is suggested by a 75-85% reduction of the hinge cleavage for variants in which His(229) was substituted with either Gln, Ser, or Ala. In contrast, mutation of Lys(227) to Gln, Ser, or Ala increased hinge cleavage. However, the H229S/K227S double mutant shows hinge cleavage levels similar to that of the single H229S variant, further revealing the importance of His(229). Examination of the hinge structure shows that His(229) is capable of forming hydrogen bonds with surrounding residues. These observations led us to hypothesize that the imidazole ring of His(229) may function to facilitate the cleavage by forming a transient radical center that is capable of extracting a proton from neighboring residues. The work presented here suggests the feasibility of engineering a new generation of monoclonal antibodies capable of resisting hinge cleavage to improve product stability and efficacy. PMID- 20304920 TI - Convertase inhibitory properties of Staphylococcal extracellular complement binding protein. AB - The human pathogen Staphylococcus aureus secretes several complement evasion molecules to combat the human immune response. Extracellular complement-binding protein (Ecb) binds to the C3d domain of C3 and thereby blocks C3 convertases of the alternative pathway and C5 convertases via all complement pathways. Inhibition of C5 convertases results in complete inhibition of C5a generation and subsequent neutrophil migration. Here, we show that binding of Ecb to the C3d domain of C3b is crucial for inhibition of C5 convertases. Ecb does not interfere with substrate binding to convertases but prevents formation of an active convertase enzyme. PMID- 20304921 TI - Regulation of hepatic six transmembrane epithelial antigen of prostate 4 (STEAP4) expression by STAT3 and CCAAT/enhancer-binding protein alpha. AB - STEAP4 is a plasma membrane metalloreductase involved in the transport of iron and copper. Recently, STEAP4 was implicated in promoting insulin sensitivity by acting in white adipose tissue to control the production of inflammatory cytokines such as interleukin 6. Indeed, the loss of STEAP4 expression in mice leads to increased production of inflammatory cytokines in visceral white adipose tissue and systemic insulin resistance. In this study, we demonstrate that in mouse liver STEAP4 is produced at significant levels and that steap4 transcription is induced by interleukin 6. We further demonstrate that the steap4 gene is a direct target of phosphorylated STAT3 in mouse liver. In addition, hepatic STEAP4 expression is regulated by feeding and fasting, and obesity leads to the induction of STEAP4 expression in the liver. Interestingly, the regulation of STEAP4 in both feeding and fasting and the obese state appears to require the transcription factor CCAAT/enhancer-binding protein alpha that may act in concert with STAT3 as they both bind to the proximal steap4 promoter in vivo. Taken together, these data suggest the transcriptional regulation of hepatic STEAP4 may play a critical role in the response to nutritional and inflammatory stress and contributes to the protective effect of STEAP4 in vivo. PMID- 20304922 TI - Post-translational modification of the NKG2D ligand RAET1G leads to cell surface expression of a glycosylphosphatidylinositol-linked isoform. AB - NKG2D is an important activating receptor on lymphocytes. In human, it interacts with two groups of ligands: the major histocompatibility complex class I chain related A/B (MICA/B) family and the UL-16 binding protein (ULBP) family, also known as retinoic acid early transcript (RAET1). MIC proteins are membrane anchored, but all of the ULBP/RAET1 proteins, except for RAET1E and RAET1G, are glycosylphosphatidylinositol (GPI)-anchored. To address the reason for these differences we studied the association of RAET1G with the membrane. Using epitope tagged RAET1G protein in conjunction with antibodies to different parts of the molecule and in pulse-chase experiments, we showed that the C terminus of the protein was cleaved soon after protein synthesis. Endoglycosidase H and peptide N glycosidase treatment and cell surface immunoprecipitation indicated that most of the protein stayed in the endoplasmic reticulum, but some of the cleaved form was modified in the Golgi and transported to the cell surface. We examined the possibility of GPI anchoring of the protein in three ways: (i) Phosphatidylinositol (PI)-specific phospholipase C released the PI-linked form of the protein. (ii) The surface expression pattern of RAET1G decreased in cells defective in GPI anchoring through mutant GPI-amidase. (iii) Site-directed mutagenesis, to disrupt residues predicted to facilitate GPI-anchoring, resulted in diminished surface expression of RAET1G. Thus, a form of RAET1G is GPI anchored, in line with most other ULBP/RAET1 family proteins. The cytoplasmic tail and transmembrane domains appear to result from gene duplication and frameshift mutation. Together with our previous results, our data suggest that RAET1G is regulated post-translationally to produce a GPI-anchored isoform. PMID- 20304923 TI - The signal peptide of the IgE receptor alpha-chain prevents surface expression of an immunoreceptor tyrosine-based activation motif-free receptor pool. AB - The high affinity receptor for IgE, Fc epsilon receptor I (FcepsilonRI), is an activating immune receptor and key regulator of allergy. Antigen-mediated cross linking of IgE-loaded FcepsilonRI alpha-chains induces cell activation via immunoreceptor tyrosine-based activation motifs in associated signaling subunits, such as FcepsilonRI gamma-chains. Here we show that the human FcepsilonRI alpha chain can efficiently reach the cell surface by itself as an IgE-binding receptor in the absence of associated signaling subunits when the endogenous signal peptide is swapped for that of murine major histocompatibility complex class-I H2 K(b). This single-chain isoform of FcepsilonRI exited the endoplasmic reticulum (ER), trafficked to the Golgi and, subsequently, trafficked to the cell surface. Mutational analysis showed that the signal peptide regulates surface expression in concert with other described ER retention signals of FcepsilonRI-alpha. Once the FcepsilonRI alpha-chain reached the cell surface by itself, it formed a ligand-binding receptor that stabilized upon IgE contact. Independently of the FcepsilonRI gamma-chain, this single-chain FcepsilonRI was internalized after receptor cross-linking and trafficked into a LAMP-1-positive lysosomal compartment like multimeric FcepsilonRI. These data suggest that the single-chain isoform is capable of shuttling IgE-antigen complexes into antigen loading compartments, which plays an important physiologic role in the initiation of immune responses toward allergens. We propose that, in addition to cytosolic and transmembrane ER retention signals, the FcepsilonRI alpha-chain signal peptide contains a negative regulatory signal that prevents expression of an immunoreceptor tyrosine-based activation motif-free IgE receptor pool, which would fail to induce cell activation. PMID- 20304924 TI - Engineering of single Ig superfamily domain of intercellular adhesion molecule 1 (ICAM-1) for native fold and function. AB - The immunoglobulin (Ig) superfamily is one of the largest families in the vertebrate genome, found most frequently in cell surface molecules. Intercellular adhesion molecule-1 (ICAM-1) contains five extracellular Ig superfamily domains (D1-D5) of which the first domain, D1, is the binding site for the integrin lymphocyte function-associated antigen-1 (LFA-1) and human rhinovirus. Despite the modular nature of many Ig superfamily domains with respect to domain folding and ligand recognition, D1 does not fold on its own due to the loss of its interaction with the second domain. The goal of this study was to engineer ICAM-1 D1 by introducing mutations that would stabilize the Ig superfamily domain fold while retaining its ability to bind to LFA-1 and rhinovirus. First, with a directed evolution approach, we isolated mutations in D1 that showed binding to conformation-specific antibodies and the ligand binding domain of LFA-1 called the inserted, or I, domain. Then, with a rational design approach we introduced mutations that contributed to the stability of ICAM-1 D1 in solution. The mutations that restored native folding of D1 in isolation were those that would convert hydrogen bond networks in buried regions into hydrophobic contacts. Notably, for most mutations, identical or similar types of substitutions were found in ICAM-1 molecules of different species and other ICAM family members. The systematic approach demonstrated in this study to engineer a single Ig superfamily fold in ICAM-1 can be broadly applicable to the engineering of modular Ig superfamily domains in other cell surface molecules. PMID- 20304925 TI - Structural analysis of the extracellular entrance to the serotonin transporter permeation pathway. AB - Neurotransmitter transporters are responsible for removal of biogenic amine neurotransmitters after release into the synapse. These transporters are the targets for many clinically relevant drugs, such as antidepressants and psychostimulants. A high resolution crystal structure for the monoamine transporters has yet to be solved. We have developed a homology model for the serotonin transporter (SERT) based on the crystal structure of the leucine transporter (LeuT(Aa)) from Aquifex aeolicus. The objective of the present studies is to identify the structural determinants forming the entrance to the substrate permeation pathway based on predictions from the SERT homology model. Using the substituted cysteine accessibility method, we identified residues predicted to reside at the entrance to the substrate permeation pathway that were reactive with methanethiosulfonate (MTS) reagents. Of these residues, Gln(332) in transmembrane helix (TMH) VI was protected against MTS inactivation in the presence of serotonin. Surprisingly, the reactivity of Gln(332) to MTS reagents was enhanced in the presence of cocaine. Bifunctional MTS cross-linkers also were used to examine the distances between helices predicted to form the entrance into the substrate and ion permeation pathway. Our studies suggest that substrate and ligand binding may induce conformational shifts in TMH I and/or VI, providing new opportunities to refine existing homology models of SERT and related monoamine transporters. PMID- 20304926 TI - Huntingtin-associated protein-1 deficiency in orexin-producing neurons impairs neuronal process extension and leads to abnormal behavior in mice. AB - Huntingtin-associated protein-1 (Hap1) is a neuronal protein that associates with huntingtin, the Huntington disease protein. Although Hap1 and huntingtin are known to be involved in intracellular trafficking, whether and how the impairment of Hap1-associated trafficking leads to neurological pathology and symptoms remain to be seen. As Hap1 is enriched in neuronal cells in the brain, addressing this issue is important in defining the role of defective intracellular trafficking in the selective neuropathology associated with Hap1 dysfunction. Here, we find that Hap1 is abundantly expressed in orexin (hypocretin)-producing neurons (orexin neurons), which are distinctly distributed in the hypothalamus and play an important role in the regulation of feeding and behavior. We created conditional Hap1 knock-out mice to selectively deplete Hap1 in orexin neurons via the Cre-loxP system. These mice show process fragmentation of orexin neurons and reductions in food intake, body weight, and locomotor activity. Sucrose density gradient fractionation reveals that loss of Hap1 in the mouse brain also reduces the distribution of trafficking protein complexes and cargo proteins in the fractions that are enriched in synaptosomes. These results suggest that Hap1 is critical for the transport of multiple proteins to the nerve terminals to maintain the integrity of neuronal processes and that selective disruption of the processes of orexin neurons can cause abnormal feeding and locomotor activity. PMID- 20304927 TI - Subunit arrangement in N-methyl-D-aspartate (NMDA) receptors. AB - N-Methyl-d-aspartate (NMDA) receptors, the main mediators of excitatory synaptic transmission, are heterotetrameric receptors. Typically, glycine binding NR1 subunits co-assemble with glutamate binding NR2 subunits to form a functional receptor. Here we have used luminescence resonance energy transfer (LRET) investigations to establish the specific configuration in which these subunits assemble to form the functional tetramer and show that the dimer of dimers structure is formed by the NR1 subunits assembling diagonally to each other. The distances measured by LRET are consistent with the NMDA structure predicted based on cross-linking investigations and on the structure of the full-length alpha amino-5-methyl-3-hydroxy-4-isoxazole propionic acid (AMPA) receptor structure (1). Additionally, the LRET distances between the NR1 and NR2A subunits within a dimer measured in the desensitized state of the receptor are longer than the distances in the previously published crystal structure of the isolated ligand binding domain of NR1-NR2A. Because the dimer interface in the isolated ligand binding domain crystallizes in the open channel structure, the longer LRET distances would be consistent with the decoupling of the dimer interface in the desensitized state. This is similar to what has been previously observed for the AMPA subtype of the ionotropic glutamate receptors, suggesting a similar mechanism for desensitization in the two subtypes of the glutamate receptor. PMID- 20304928 TI - Oligomeric size of the m2 muscarinic receptor in live cells as determined by quantitative fluorescence resonance energy transfer. AB - Fluorescence resonance energy transfer (FRET), measured by fluorescence intensity based microscopy and fluorescence lifetime imaging, has been used to estimate the size of oligomers formed by the M(2) muscarinic cholinergic receptor. The approach is based on the relationship between the apparent FRET efficiency within an oligomer of specified size (n) and the pairwise FRET efficiency between a single donor and a single acceptor (E). The M(2) receptor was fused at the N terminus to enhanced green or yellow fluorescent protein and expressed in Chinese hamster ovary cells. Emission spectra were analyzed by spectral deconvolution, and apparent efficiencies were estimated by donor-dequenching and acceptor sensitized emission at different ratios of enhanced yellow fluorescent protein M(2) receptor to enhanced green fluorescent protein-M(2) receptor. The data were interpreted in terms of a model that considers all combinations of donor and acceptor within a specified oligomer to obtain fitted values of E as follows: n = 2, 0.495 +/- 0.019; n = 4, 0.202 +/- 0.010; n = 6, 0.128 +/- 0.006; n = 8, 0.093 +/- 0.005. The pairwise FRET efficiency determined independently by fluorescence lifetime imaging was 0.20-0.24, identifying the M(2) receptor as a tetramer. The strategy described here yields an explicit estimate of oligomeric size on the basis of fluorescence properties alone. Its broader application could resolve the general question of whether G protein-coupled receptors exist as dimers or larger oligomers. The size of an oligomer has functional implications, and such information can be expected to contribute to an understanding of the signaling process. PMID- 20304929 TI - Dominant negative mutations affect oligomerization of human pyruvate kinase M2 isozyme and promote cellular growth and polyploidy. AB - This study was designed to understand the mechanism and functional implication of the two heterozygous mutations (H391Y and K422R) of human pyruvate kinase M2 isozyme (PKM(2)) observed earlier in a Bloom syndrome background. The co expression of homotetrameric wild type and mutant PKM(2) in the cellular milieu resulting in the interaction between the two at the monomer level was substantiated further by in vitro experiments. The cross-monomer interaction significantly altered the oligomeric state of PKM(2) by favoring dimerization and heterotetramerization. In silico study provided an added support in showing that hetero-oligomerization was energetically favorable. The hetero-oligomeric populations of PKM(2) showed altered activity and affinity, and their expression resulted in an increased growth rate of Escherichia coli as well as mammalian cells, along with an increased rate of polyploidy. These features are known to be essential to tumor progression. This study provides insight in understanding the modulated role of large oligomeric multifunctional proteins such as PKM(2) by affecting cellular behavior, which is an essential observation to understand tumor sustenance and progression and to design therapeutic intervention in future. PMID- 20304931 TI - Hidden function of catalytic domain in 6-methylsalicylic acid synthase for product release. AB - Functional investigation of the proposed dehydratase domain of ATX, a 6 methylsalicylic acid synthase from Aspergillus terreus, revealed that the domain is not involved in dehydration of the beta-hydroxytriketide intermediate tethered on the acyl carrier protein but catalyzes thioester hydrolysis to release the product from the acyl carrier protein. Thus, we renamed this domain the thioester hydrolase (TH) domain. The intermediate bound to the TH domain of mutant H972A formed in the presence of NADPH was released as 6-methylsalicylic acid by both the intact ATX and by THID (a 541-amino acid region containing TH domain and its downstream) protein, in trans. Furthermore, THID showed a catalytic activity to hydrolyze a model substrate, 6-methylsalicylic acid-N-acetylcysteamine. The TH domain is the first example of a product-releasing domain that is located in the middle of a multidomain iterative type I polyketide synthase. Moreover, it is functionally different from serine protease-type thioesterase domains of iterative type I polyketide synthases. PMID- 20304930 TI - Phosphatidic acid is a leukocyte chemoattractant that acts through S6 kinase signaling. AB - Phosphatidic acid (PA) is a pleiotropic lipid second messenger in mammalian cells. We report here that extracellular PA acts as a leukocyte chemoattractant, as membrane-soluble dioleoyl-PA (DOPA) elicits actin polymerization and chemotaxis of human neutrophils and differentiated proleukemic HL-60 cells. We show that the mechanism for this involves the S6 kinase (S6K) signaling enzyme. Chemotaxis was inhibited >90% by the S6K inhibitors rapamycin and bisindolylmaleimide and by S6K1 silencing using double-stranded RNA. However, it was only moderately ( approximately 30%) inhibited by mTOR siRNA, indicating the presence of an mTOR-independent mechanism for S6K. Exogenous PA led to robust time- and dose-dependent increases in S6K enzymatic activity and Thr(421)/Ser(424) phosphorylation, further supporting a PA/S6K connection. We also investigated whether intracellular PA production affects cell migration. Overexpression of phospholipase D2 (PLD2) and, to a lesser extent, PLD1, resulted in elevation of both S6K activity and chemokinesis, whereas PLD silencing was inhibitory. Because the lipase-inactive PLD2 mutants K444R and K758R neither activated S6K nor induced chemotaxis, intracellular PA is needed for this form of cell migration. Lastly, we demonstrated a connection between extracellular and intracellular PA. Using an enhanced green fluorescent protein-derived PA sensor (pEGFP-Spo20PABD), we showed that exogenous PA or PA generated in situ by bacterial (Streptomyces chromofuscus) PLD enters the cell and accumulates in vesicle-like cytoplasmic structures. In summary, we report the discovery of PA as a leukocyte chemoattractant via cell entry and activation of S6K to mediate the cytoskeletal actin polymerization and leukocyte chemotaxis required for the immune function of these cells. PMID- 20304934 TI - Rethinking pragmatic randomised controlled trials: introducing the "cohort multiple randomised controlled trial" design. PMID- 20304932 TI - Therapeutic strategies for targeting excessive central sympathetic activation in human hypertension. AB - The pathogenesis of hypertension and its mode of progression are complex, multifactoral and incompletely understood. However, there is accumulating evidence from humans and animal models of hypertension indicating that excessive central sympathetic nerve activity (SNA) plays a pathogenic role in triggering and sustaining the essential hypertensive state (the so-called 'neuroadrenergic hypothesis'). Importantly, augmented central sympathetic outflow has also been implicated in the initiation and progression of a plethora of pathophysiological processes independent of any increase in blood pressure, such as left ventricular hypertrophy and cardiac arrhythmias. Thus, the sympathetic nervous system constitutes an important putative drug target in hypertension. However, traditional pharmacological approaches for the management of essential hypertension appear ineffective in reducing central sympathetic outflow. Recently, several new and promising therapeutic strategies targeting neurogenic hypertension have been developed. The present report will provide a brief update of this topic with a particular emphasis on human studies examining the efficacy of novel pharmacological approaches (central sympatholytics and statins), lifestyle modification (aerobic exercise training, weight loss and stress reduction) and surgical intervention (renal denervation, chronic carotid baroreflex stimulation and deep brain stimulation) in reducing excessive central sympathetic activation in hypertension. PMID- 20304935 TI - Subjective memory problems. PMID- 20304939 TI - Kinetic analysis of the cooperation of P-glycoprotein (P-gp/Abcb1) and breast cancer resistance protein (Bcrp/Abcg2) in limiting the brain and testis penetration of erlotinib, flavopiridol, and mitoxantrone. AB - A synergistic effect of P-glycoprotein (P-gp)/Abcb1a and breast cancer resistance protein (Bcrp)/Abcg2 was reported to limit the brain penetration of their common substrates. This study investigated this based on pharmacokinetics using Mdr1a/1b(-/-), Bcrp(-/-), and Mdr1a/1b(-/-)/Bcrp(-/-) mice. Comparison of the brain- and testis-to-plasma ratios (C(brain)/C(plasma) and C(testis)/C(plasma), respectively) of the reference compounds quinidine and dantrolene for P-gp and Bcrp, respectively, indicates that impairment of either P-gp and Bcrp did not cause any change in the efflux activities of Bcrp or P-gp, respectively, at both the blood-brain barrier (BBB) and blood-testis barrier (BTB). The C(brain)/C(plasma) and C(testis)/C(plasma) of the common substrates erlotinib, flavopiridol, and mitoxantrone were markedly increased in Mdr1a/1b(-/-)/Bcrp(-/-) mice even compared with Mdr1a/1b(-/-) and Bcrp(-/-) mice. Efflux activities by P gp and Bcrp relative to passive diffusion at the BBB and BTB were separately evaluated based on the C(brain)/C(plasma) and C(testis)/C(plasma) in the knockout strains to the wild-type strain. P-gp made a larger contribution than Bcrp to the net efflux of the common substrates, but Bcrp activities were also significantly larger than passive diffusion. These parameters could reasonably account for the marked increase in C(brain)/C(plasma) and C(testis)/C(plasma) in the Mdr1a/1b(-/ )/Bcrp(-/-) mice. In conclusion, the synergistic effect of P-gp and Bcrp on C(brain)/C(plasma) and C(testis)/C(plasma) can be explained by their contribution to the net efflux at the BBB and BTB without any interaction between P-gp and Bcrp. PMID- 20304938 TI - A functional role for nicotinic acid adenine dinucleotide phosphate in oxytocin mediated contraction of uterine smooth muscle from rat. AB - Conventionally, G protein-coupled receptors are thought to increase calcium via inositol 1,4,5-trisphosphate (InsP(3)). More recent evidence shows that an alternative second messenger, nicotinic acid adenine dinucleotide phosphate (NAADP), also has a role to play, causing researchers to question established calcium releasing pathways. With the recent development, by our group, of cell permeant NAADP (NAADP-aceteoxymethyl ester) and a selective NAADP receptor antagonist (Ned-19; 1-(3-((4-(2-fluorophenyl)piperazin-1-yl)methyl)-4 methoxyphenyl)-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole-3-carboxylic acid),the ability to investigate this signaling pathway has improved. Therefore, we investigated a role for NAADP in oxytocin-mediated responses in the rat uterus. Oxytocin- and NAADP-mediated effects were investigated by using contractile measurements of whole uterine strips from rat in organ baths. Responses were correlated to calcium release in cultured rat uterine smooth muscle cells measured by fluorescence microscopy. Inhibition of both oxytocin-induced contraction and calcium release by the traditional NAADP-signaling disrupter bafilomycin and the NAADP receptor antagonist Ned-19 clearly demonstrated a role for NAADP in oxytocin-induced signaling. A cell-permeant form of NAADP was able to produce both uterine contractions and calcium release. This response was unaffected by depletion of sarcoplasmic reticulum stores with thapsigargin, but was abolished by both bafilomycin and Ned-19. Crucially, oxytocin stimulated an increase in NAADP in rat uterine tissue. The present study demonstrates directly that NAADP signaling plays a role in rat uterine contractions. Moreover, investigation of this signaling pathway highlights yet another component of oxytocin-mediated signaling, stressing the need to consider the action of new components as they are discovered, even in signaling pathways that are thought to be well established. PMID- 20304941 TI - Surpassing specificity limits of nucleic acid probes via cooperativity. AB - The failure to correctly identify single nucleotide polymorphisms (SNPs) significantly contributes to the misdiagnosis of infectious disease. Contrary to the strategy of creating shorter probes to improve SNP differentiation, we created larger probes that appeared to increase selectivity. Specifically, probes with enhanced melting temperature differentials (>13x improvement) to SNPs were generated by linking two probes that consist of both a capture sequence and a detection sequence; these probes act cooperatively to improve selectivity over a wider range of reaction conditions. These cooperative probe constructs (Tentacle probes) were then compared by modeling thermodynamic and hybridization characteristics to both Molecular Beacons (stem loop DNA probes) and Taqman probes (a linear oligonucleotide). The biophysical models reveal that cooperative probes compared with either Molecular beacons or Taqman probes have enhanced specificity. This was a result of increased melting temperature differentials and the concentration-independent hybridization revealed between wild-type and variant sequences. We believe these findings of order of magnitude enhanced melting temperature differentials with probes possessing concentration independence and more favorable binding kinetics have the potential to significantly improve molecular diagnostic assay functionality. PMID- 20304940 TI - Nitro-oleic acid inhibits firing and activates TRPV1- and TRPA1-mediated inward currents in dorsal root ganglion neurons from adult male rats. AB - Nitro-oleic acid (OA-NO(2)), an electrophilic fatty acid by-product of nitric oxide and nitrite reactions, is present in normal and inflamed mammalian tissues at up to micromolar concentrations and exhibits anti-inflammatory signaling actions. The effects of OA-NO(2) on cultured dorsal root ganglion (DRG) neurons were examined using fura-2 Ca(2+) imaging and patch clamping. OA-NO(2) (3.5-35 microM) elicited Ca(2+) transients in 20 to 40% of DRG neurons, the majority (60 80%) of which also responded to allyl isothiocyanate (AITC; 1-50 microM), a TRPA1 agonist, and to capsaicin (CAPS; 0.5 microM), a TRPV1 agonist. The OA-NO(2) evoked Ca(2+) transients were reduced by the TRPA1 antagonist 2-(1,3-dimethyl-2,6 dioxo-1,2,3,6-tetrahydro-7H-purin-7-yl)-N-(4-isopropylphenyl) acetamide (HC 030031; 5-50 microM) and the TRPV1 antagonist capsazepine (10 microM). Patch clamp recording revealed that OA-NO(2) depolarized and induced inward currents in 62% of neurons. The effects of OA-NO(2) were elicited by concentrations >or=5 nM and were blocked by 10 mM dithiothreitol. Concentrations of OA-NO(2) >or=5 nM reduced action potential (AP) overshoot, increased AP duration, inhibited firing induced by depolarizing current pulses, and inhibited Na(+) currents. The effects of OA-NO(2) were not prevented or reversed by the NO-scavenger carboxy-2-phenyl 4,4,5,5-tetramethylimidazolineoxyl-1-oxyl-3-oxide. A large percentage (46-57%) of OA-NO(2)-responsive neurons also responded to CAPS (0.5 microM) or AITC (0.5 microM). OA-NO(2) currents were reduced by TRPV1 (diarylpiperazine; 5 microM) or TRPA1 (HC-030031; 5 microM) antagonists. These data reveal that endogenous OA NO(2) generated at sites of inflammation may initially activate transient receptor potential channels on nociceptive afferent nerves, contributing to the initiation of afferent nerve activity, and later suppresses afferent firing. PMID- 20304942 TI - Towards routine screening of rare genetic diseases: the example of chronic granulomatous disease. PMID- 20304943 TI - Development of a diagnostic microarray assay to assess the risk of recurrence of prostate cancer based on PITX2 DNA methylation. AB - Prostate cancer is among the most common cancers. Although it has a relatively good prognosis, 15 to 30% of men with prostate cancer experience a relapse after radical prostatectomy. Identifying patients with an aggressive tumor will therefore help to improve prostate cancer management. DNA methylation of PITX2 has been established in several studies as a prognostic biomarker for breast and prostate cancer. These case control studies were conducted using research assay components; to facilitate its use in a diagnostic setting, the PITX2 biomarker was transferred to a validated diagnostic platform, the Affymetrix GeneChip System. A customized microarray (Epichip PITX2) was designed using features in high redundancy to ensure a robust determination of the methylation state of the PITX2 promoter. The developed method allowed for accurate assessment of prognosis in prostate cancer patients who underwent radical prostatectomy. Determination of PITX2 methylation in formalin-fixed and paraffin-embedded tissue samples from a cohort of 157 prostatectomy patients resulted in an excellent level of concordance of the clinical classification, as well as the measured output between the research assay and the Epichip PITX2. These analytical performance results describe the Epichip PITX2 as a robust and reliable diagnostic tool for assessing the methylation status of PITX2, enabling an improved outcome prediction in cancer patients following radical prostatectomy. PMID- 20304949 TI - Therapeutic potential of proteasome inhibition in Duchenne and Becker muscular dystrophies. AB - Duchenne muscular dystrophy (DMD) and its milder allelic variant, Becker muscular dystrophy (BMD), result from mutations of the dystrophin gene and lead to progressive muscle deterioration. Enhanced activation of proteasomal degradation underlies critical steps in the pathogenesis of the DMD/BMD dystrophic process. Previously, we demonstrated that treatment with the proteasome inhibitor MG-132 rescues the cell membrane localization of dystrophin and the dystrophin glycoprotein complex in mdx mice, a natural genetic mouse model of DMD. The current work aims to thoroughly define the therapeutic potential in dystrophinopathies of Velcade, a drug that selectively blocks the ubiquitin proteasome pathway. Velcade is particularly intriguing since it has been approved for the treatment of multiple myeloma. Therefore, its side effects in humans have been explored. Velcade effects were analyzed through two independent methodological approaches. First, we administered the drug systemically in mdx mice over a 2-week period. In this system, Velcade restores the membrane expression of dystrophin and dystrophin glycoprotein complex members and improves the dystrophic phenotype. In a second approach, we treated with the compound explants from muscle biopsies of DMD or BMD patients. We show that the inhibition of the proteasome pathway up-regulates dystrophin, alpha-sarcoglycan, and beta dystroglycan protein levels in explants from BMD patients, whereas it increases the proteins of the dystrophin glycoprotein complex in DMD cases. PMID- 20304950 TI - Reduction of IKKalpha expression promotes chronic ultraviolet B exposure-induced skin inflammation and carcinogenesis. AB - Ultraviolet B light (UVB) is a common cause of human skin cancer. UVB irradiation induces mutations in the tumor suppressor p53 gene as well as chronic inflammation, which are both essential for UVB carcinogenesis. Inhibitor of nuclear factor kappaB kinase-alpha (IKKalpha) plays an important role in maintaining skin homeostasis, and expression of IKKalpha was found to be down regulated in human and murine skin squamous cell carcinomas. However, the role of IKKalpha in UVB skin carcinogenesis has not been investigated. Thus, here we performed UVB carcinogenesis experiments on Ikkalpha(+/+) and Ikkalpha(+/-) mice. Ikkalpha(+/-) mice were found to develop a twofold greater number of skin tumors than Ikkalpha(+/+) mice after chronic UVB irradiation. In addition, tumor latency was significantly shorter and tumors were bigger in Ikkalpha(+/-) than in Ikkalpha(+/+) mice. At an early stage of carcinogenesis, an increase in UVB induced p53 mutations as well as macrophage recruitment and mitogenic activity, and a decrease in UVB-induced apoptosis, were detected in Ikkalpha(+/-) compared with those in Ikkalpha(+/+) skin. Also, reduction of IKKalpha levels in keratinocytes up-regulated the expression of monocyte chemoattractant protein-1 (MCP-1/CCL2), TNFalpha, IL-1, and IL-6, and elevated macrophage migration, which might promote macrophage recruitment and inflammation. Therefore, these findings suggest that reduction of IKKalpha expression orchestrates UVB carcinogen, accelerating tumorigenesis. PMID- 20304951 TI - Macrophages protect against muscle atrophy and promote muscle recovery in vivo and in vitro: a mechanism partly dependent on the insulin-like growth factor-1 signaling molecule. AB - Hindlimb unloading and reloading are characterized by a major loss of muscle force and are associated with classic leukocyte infiltration during recovery from muscle atrophy. Macrophages act as a cellular cornerstone by playing both pro- and anti-inflammatory roles during muscle recovery from atrophy. In the present study, we investigated the role of macrophages in muscle atrophy and regrowth using in vivo and in vitro models. Mice depleted in monocytes/macrophages and submitted to a hindlimb unloading and reloading protocol experienced a significant delay in muscle force recovery compared with matched placebo mice at 7 and 14 days after reloading. Furthermore, an in vitro myotube/macrophage coculture showed that anti-inflammatory macrophages, which contain apoptotic neutrophils and express low levels of cyclooxygenase-2, completely prevented the loss of protein content and the myotube atrophy observed after 2 days in low serum medium. The presence of macrophages also protected against the decrease in myosin heavy chain content in myotubes exposed to low serum medium for 1 day. Interestingly, the addition of an anti-IGF-1 antibody to the coculture significantly decreased the ability of macrophages to protect against myotube atrophy and myosin heavy chain loss after 2 days in low serum medium. These results clearly indicate that macrophages and, more precisely, the release of IGF 1 by macrophages, play an important role in recovery from muscle atrophy. PMID- 20304952 TI - Dendritic cells produce CXCL13 and participate in the development of murine small intestine lymphoid tissues. AB - In the adult intestine, luminal microbiota induce cryptopatches to transform into isolated lymphoid follicles (ILFs), which subsequently act as sites for the generation of IgA responses. The events leading to this conversion are incompletely understood. Dendritic cells (DCs) are components of cryptopatches (CPs) and ILFs and were therefore evaluated in this process. We observed that the adult murine intestine contains clusters of DCs restricted to the CP/ILF continuum. A numerical and cell associative hierarchy in the adult intestine and a chronologic hierarchy in the neonatal intestine demonstrated that these clusters form after the coalescence of CD90+ cells to form CPs and before the influx of B220+ B lymphocytes to form ILFs. Cluster formation was dependent on lymphotoxin and the lymphotoxin beta receptor and independent of lymphocytes. The ILF DC population was distinguished from that of the lamina propria by the absence of CD4+CD11c+ cells and an increased proportion of CD11c+B220+ cells. The formation of clusters was not limited by DC numbers but was induced by luminal microbiota. Moreover, in the absence of the chemokine CXCL13, CP transformation into ILF was arrested. Furthermore, ILF DCs express CXCL13, and depletion of DCs resulted in regression of ILFs and disorganization of CPs. These results reveal DC participation in ILF transformation and maintenance and suggest that in part this may be due to CXCL13 production by these cells. PMID- 20304954 TI - MicroRNA-193b represses cell proliferation and regulates cyclin D1 in melanoma. AB - Cutaneous melanoma is an aggressive form of human skin cancer characterized by high metastatic potential and poor prognosis. To better understand the role of microRNAs (miRNAs) in melanoma, the expression of 470 miRNAs was profiled in tissue samples from benign nevi and metastatic melanomas. We identified 31 miRNAs that were differentially expressed (13 up-regulated and 18 down-regulated) in metastatic melanomas relative to benign nevi. Notably, miR-193b was significantly down-regulated in the melanoma tissues examined. To understand the role of miR 193b in melanoma, functional studies were undertaken. Overexpression of miR-193b in melanoma cell lines repressed cell proliferation. Gene expression profiling identified 314 genes down-regulated by overexpression of miR-193b in Malme-3M cells. Eighteen of these down-regulated genes, including cyclin D1 (CCND1), were also identified as putative miR-193b targets by TargetScan. Overexpression of miR 193b in Malme-3M cells down-regulated CCND1 mRNA and protein by > or = 50%. A luciferase reporter assay confirmed that miR-193b directly regulates CCND1 by binding to the 3'untranslated region of CCND1 mRNA. These studies indicate that miR-193b represses cell proliferation and regulates CCND1 expression and suggest that dysregulation of miR-193b may play an important role in melanoma development. PMID- 20304955 TI - Genetic background affects properties of satellite cells and mdx phenotypes. AB - Duchenne muscular dystrophy (DMD) is the most common lethal genetic disorder of children. The mdx (C57BL/10 background, C57BL/10-mdx) mouse is a widely used model of DMD, but the histopathological hallmarks of DMD, such as the smaller number of myofibers, accumulation of fat and fibrosis, and insufficient regeneration of myofibers, are not observed in adult C57BL/10-mdx except for in the diaphragm. In this study, we showed that DBA/2 mice exhibited decreased muscle weight, as well as lower myofiber numbers after repeated degeneration regeneration cycles. Furthermore, the self-renewal efficiency of satellite cells of DBA/2 is lower than that of C57BL/6. Therefore, we produced a DBA/2-mdx strain by crossing DBA/2 and C57BL/10-mdx. The hind limb muscles of DBA/2-mdx mice exhibited lower muscle weight, fewer myofibers, and increased fat and fibrosis, in comparison with C57BL/10-mdx. Moreover, remarkable muscle weakness was observed in DBA/2-mdx. These results indicate that the DBA/2-mdx mouse is a more suitable model for DMD studies, and the efficient satellite cell self-renewal ability of C57BL/10-mdx might explain the difference in pathologies between humans and mice. PMID- 20304956 TI - Epithelial to mesenchymal transition in human skin wound healing is induced by tumor necrosis factor-alpha through bone morphogenic protein-2. AB - Epithelial-mesenchymal transition (EMT), characterized by loss of epithelial adhesion and gain of mesenchymal features, is an important mechanism to empower epithelial cells into the motility that occurs during embryonic development and recurs in cancer and fibrosis. Whether and how EMT occurs in wound healing and fibrosis in human skin remains unknown. In this study we found that migrating epithelial cells in wound margins and deep epithelial ridges had gained mesenchymal features such as vimentin and FSP1 expression. In hypertrophic scars, EMT-related genes were elevated along with inflammatory cytokines, indicating a causal relationship. To reconstitute EMT in vitro, normal human skin and primary keratinocytes were exposed to cytokines such as tumor necrosis factor-alpha (TNF alpha), resulting in expression of vimentin, FSP1, and matrix metalloproteinases. Moreover, TNF-alpha-induced EMT was impaired by antagonists against bone morphogen proteins (BMP) 2/4, suggesting that BMP mediates the TNF-alpha-induced EMT in human skin. Indeed, TNF-alpha could induce BMP-2 and its receptor (BMPR1A) in human skin and primary keratinocytes, and BMP2 could induce EMT features in skin explants and primary keratinocytes. In summary, we uncovered EMT features in both acute and fibrotic cutaneous wound healing of human skin. Moreover, we propose that the mesenchymal induction in wound healing is motivated by TNF alpha, in part, through induction of BMP. PMID- 20304957 TI - A role for the high-density lipoprotein receptor SR-B1 in synovial inflammation via serum amyloid-A. AB - Acute phase apoprotein Serum Amyloid A (A-SAA), which is strongly expressed in rheumatoid arthritis synovial membrane (RA SM), induces angiogenesis, adhesion molecule expression, and matrix metalloproteinase production through the G coupled receptor FPRL-1. Here we report alternative signaling through the high density lipoprotein receptor scavenger receptor-class B type 1 (SR-B1). Quantitative expression/localization of SR-B1 in RA SM, RA fibroblast-like cells (FLCs), and microvascular endothelial cells (ECs) was assessed by Western blotting and immunohistology/fluorescence. A-SAA-mediated effects were examined using a specific antibody against SR-B1 or amphipathic alpha-Helical Peptides (the SR-B1 antagonists L-37pA and D-37pA), in RA FLCs and ECs. Adhesion molecule expression and cytokine production were quantified using flow cytometry and ELISA. SR-B1 was strongly expressed in the RA SM lining layer and endothelial/perivascular regions compared with osteoarthritis SM or normal control synovium. Differential SR-B1 expression in RA FLC lines (n = 5) and ECs correlated closely with A-SAA, but not tumor necrosis factor alpha-induced intercellular adhesion molecule-1 upregulation. A-SAA-induced interleukin-6 and 8 production was inhibited in the presence of anti-SR-B1 in human microvascular endothelial cells and RA FLCs. Moreover, D-37pA and L-37pA inhibited A-SAA induced vascular cell adhesion molecule-1 and intercellular adhesion molecule expression from ECs in a dose-dependent manner. As SR-B1 is expressed in RA synovial tissue and mediates A-SAA-induced pro-inflammatory pathways, a better understanding of A-SAA-mediated inflammatory pathways may lead to novel treatment strategies for RA. PMID- 20304958 TI - Cathepsin L in bone marrow-derived cells is required for retinal and choroidal neovascularization. AB - Many vision-threatening diseases are characterized by intraocular neovascularization, (e.g., proliferative diabetic retinopathy and age-related macular degeneration). Although a new therapy with anti-VEGF antibodies is being used to treat these intraocular neovascular disorders, the visual recovery is limited, mainly because of the remnants of fibrovascular tissues. The ideal goal of the treatment is to prevent the invasion of new vessels into the avascular tissue through a matrix barrier. The purpose of this study was to determine the role played by cathepsin L, a matrix degrading enzyme, on intraocular angiogenesis. Used established animal models of retinal and choroidal neovascularization, we demonstrated that an inhibition of cathepsin L by specific inhibitors resulted in a significant decrease of intraocular neovascularization. A similar decrease of neovascularization was found in cathepsin L-deficient mice. Transplantation of bone marrow from cathepsin L-deficient mice into wild-type mice significantly reduced the degree of intraocular neovascularization. In addition, immunocytochemical analyses demonstrated that VE cadherin-positive endothelial progenitor cells, but not CD43-positive or Iba-1-positive cells, were the major cells contributing to the production of cathepsin L. These data indicate that cathepsin L expressed in endothelial progenitor cells plays a critical role in intraocular angiogenesis and suggest a potential therapeutic approach of targeting cathepsin L for neovascular ocular diseases. PMID- 20304959 TI - Ventilator-induced inflammatory response in lipopolysaccharide-exposed rat lung is mediated by angiotensin-converting enzyme. AB - Angiotensin-converting enzyme (ACE) mediates the ventilator-induced inflammatory response in healthy lungs via angiotensin II (Ang II). A rat model was used to examine the role of ACE and Ang II in the inflammatory response during mechanical ventilation of preinjured (ie, lipopolysaccharide [LPS]-exposed) lungs. When indicated, rats were pretreated with the ACE inhibitor captopril and/or intratracheal administration of LPS. The animals were ventilated for 4 hours with moderate pressure amplitudes. Nonventilated animals served as controls. ACE activity and levels of Ang II and inflammatory mediators (interleukin-6, Cytokine induced Neutrophil Chemoattractant (CINC)-3, interleukin-1beta, and interleukin 10) were determined in bronchoalveolar lavage fluid (BALF). The localization of ACE and Ang II type 1 receptor in lung tissue was determined by immunohistochemistry. The role of the Ang II pathway was assessed by using its receptor antagonist Losartan. Mechanical ventilation of LPS-exposed animals increased ACE activity and levels of inflammatory mediators in BALF compared with ventilated nonexposed and LPS-exposed nonventilated animals. Blocking ACE by captopril attenuated the lung inflammatory response. Furthermore, increased ACE activity in BALF was accompanied by increased levels of Ang II and enhanced expression of its receptor on alveolar cells. Blocking the Ang II receptor attenuated the inflammatory mediator response to a larger extent than by blocking ACE. In conclusion, during mechanical ventilation ACE, via Ang II, mediates the inflammatory response of both healthy and preinjured lungs. PMID- 20304960 TI - Flaky tail mouse denotes human atopic dermatitis in the steady state and by topical application with Dermatophagoides pteronyssinus extract. AB - The barrier abnormality, a loss-of-function mutation in the gene encoding filaggrin (FLG), which is linked to the incidence of atopic dermatitis (AD), is a recently discovered but important factor in the pathogenesis of AD. Flaky tail (Flg(ft)) mice, essentially deficient in filaggrin, have been used to investigate the role of filaggrin on AD. However, the relevancy of Flg(ft) mice to human AD needs to be determined further. In this study, we observed the clinical manifestations of Flg(ft) mice in the steady state and their cutaneous immune responses against external stimuli, favoring human AD. Under specific pathogen free conditions, the majority of Flg(ft) mice developed clinical and histological eczematous skin lesions similar to human AD with outside-to-inside skin barrier dysfunction evaluated by newly devised methods. In addition, cutaneous hapten induced contact hypersensitivity as a model of acquired immune response and a mite extract-induced dermatitis model physiologically relevant to a human AD were enhanced in Flg(ft) mice. These results suggest that the Flg(ft) mouse genotype has potential as an animal model of AD corresponding with filaggrin mutation in human AD. PMID- 20304961 TI - Caveolin-1 deficiency dampens Toll-like receptor 4 signaling through eNOS activation. AB - Caveolin-1 (Cav1), the scaffolding protein of caveolae, has been shown to play an important role in host defense and inflammation. However, the underlying molecular basis for these actions remains elusive. Here, using double mutant mice with genetic deletions of Cav1 and NOS3, we show that chronic endothelial nitric oxide synthase (eNOS) activation secondary to loss of Cav1 serves a crucial immunomodulatory function through tyrosine nitration-mediated impairment of interleukin-1 receptor associated kinase (IRAK)4, a signaling component required for nuclear factor-kappaB activation and innate immunity. We observed an eNOS dependent decrease in the plasma concentration of pro-inflammatory cytokines and marked improvement of survival in Cav1(-/-) mice following lipopolysaccharide challenge. Activation of eNOS secondary to loss of Cav1 resulted in decreased activation of nuclear factor-kappaB in response to lipopolysaccharide challenge, and thereby protected the animals from lipopolysaccharide-induced lung injury. IRAK4 was prominently nitrated in Cav1-deficient endothelial cells, whereas eNOS deletion in Cav1-deficient endothelial cells resulted in marked decrease of IRAK4 nitration and restored the inflammatory response after lipopolysaccharide challenge. Furthermore, in vitro nitration of IRAK4 resulted in impairment of the kinase activity. Thus, eNOS activation secondary to loss of Cav1 signals dampening of the innate immune response to lipopolysaccharide through IRAK4 nitration and the resultant impairment of kinase activity, and consequently mitigates inflammatory lung injury. PMID- 20304962 TI - Synoviocyte-derived angiopoietin-like protein 2 contributes to synovial chronic inflammation in rheumatoid arthritis. AB - Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by symmetrical polyarticular synovitis of the diarthrodial joints. Several proinflammatory cytokines derived from both infiltrating inflammatory cells and activated resident cells within the RA joint play a fundamental role in the processes that cause inflammation. However, anticytokine treatment is beneficial but not curative, the effects are only partial, and nonresponses are common. Therefore, an effort has been made to identify other key regulators of inflammation in articular structures to develop new therapies to suppress synovial inflammation and joint destruction in RA. Adipose tissue-derived angiopoietin-like protein 2 (Angptl2) activates an inflammatory cascade in endothelial cells and induces chemotaxis of monocytes/macrophages in obesity, resulting in initiation and propagation of inflammation within adipose tissues and obesity-related metabolic diseases. Angptl2 mRNA and protein are abundantly expressed in hyperplastic rheumatoid synovium of RA patients, especially in fibroblast-like and macrophage-like synoviocytes, but not in B and T lymphocytes. Angptl2 concentration in joints of RA patients was also significantly increased in comparison with patients with osteoarthritis, which in comparison with RA represents a significantly lower inflammatory grade form of arthritis. Notably, Angptl2 promoted increased chemotactic activities of CD14+CD16- monocytes from synovial fluid of RA patients. Therefore, Angptl2 acts as an important rheumatoid synovium-derived inflammatory mediator in RA pathogenesis. PMID- 20304963 TI - The LTB4-BLT1 axis mediates neutrophil infiltration and secondary injury in experimental spinal cord injury. AB - Traumatic injury in the central nervous system induces inflammation; however, the role of this inflammation is controversial. Precise analysis of the inflammatory cells is important to gain a better understanding of the inflammatory machinery in response to neural injury. Here, we demonstrated that leukotriene B4 plays a significant role in mediating leukocyte infiltration after spinal cord injury. Using flow cytometry, we revealed that neutrophil and monocyte/macrophage infiltration peaked 12 hours after injury and was significantly suppressed in leukotriene B4 receptor 1 knockout mice. Similar findings were observed in mice treated with a leukotriene B4 receptor antagonist. Further, by isolating each inflammatory cell subset with a cell sorter, and performing quantitative reverse transcription-PCR, we demonstrated the individual contributions of more highly expressed subsets, ie, interleukins 6 and 1beta, tumor necrosis factor-alpha, and FasL, to the inflammatory reaction and neural apoptosis. Inhibition of leukotriene B4 suppressed leukocyte infiltration after injury, thereby attenuating the inflammatory reaction, sparing the white matter, and reducing neural apoptosis, as well as inducing better functional recovery. These findings are the first to demonstrate that leukotriene B4 is involved in the pathogenesis of spinal cord injury through the amplification of leukocyte infiltration, and provide a potential therapeutic strategy for traumatic spinal cord injury. PMID- 20304964 TI - The NADPH oxidase subunit p22phox inhibits the function of the tumor suppressor protein tuberin. AB - Mutations in the von Hippel-Lindau (VHL) gene give rise to renal cell carcinoma. Reactive oxygen species, generated by Nox oxidases, are involved in tumorigenesis. We have previously demonstrated that in VHL-deficient cells, p22(phox)-dependent Nox1 and Nox4 oxidases maintain hypoxia inducible factor 2alpha (HIF-2alpha) protein expression through an Akt-dependent translational pathway. Phosphorylation of tuberin, by Akt, results in its inactivation. Here we show that diphenyleneiodonium chloride, an inhibitor of Nox oxidases, and small interfering RNA-mediated down-regulation of p22(phox) inhibit Akt-dependent phosphorylation of tuberin and stabilizes tuberin protein levels in VHL-deficient renal carcinoma cells. p22(phox)-mediated inactivation of tuberin is associated with an increase in ribosomal protein S6 kinase 1 and eukaryotic initiation factor 4E-binding protein-1 (4E-BP1) phosphorylation as well as HIF-2alpha stabilization. Importantly, we find that marked up-regulation of p22(phox) in human renal cell carcinoma correlates with increased tuberin phosphorylation, decreased tuberin protein levels, and increased phosphorylation of 4E-BP1. Our data provide the first evidence that p22(phox)-based Nox oxidases maintain HIF 2alpha protein expression through inactivation of tuberin and downstream activation of ribosomal protein S6 kinase 1/4E-BP1 pathway. PMID- 20304965 TI - Investigation into UDP-glucuronosyltransferase (UGT) enzyme kinetics of imidazole and triazole-containing antifungal drugs in human liver microsomes and recombinant UGT enzymes. AB - Imidazoles and triazoles represent major classes of antifungal azole derivatives. With respect to UDP-glucuronosyltransferase (UGT) enzymes, the drug metabolism focus has mainly concentrated on their inhibitory effects with little known about azoles as substrates for UGTs. N-Glucuronide metabolites of the imidazole antifungals, tioconazole and croconazole, have been reported, but there are currently no reports of N-glucuronidation of triazole antifungal agents. In this study, evidence for glucuronidation of azole-containing compounds was studied in human liver microsomes (HLM). When a glucuronide metabolite was identified, azoles were incubated in 12 recombinant UGT (rUGT) enzymes, and enzyme kinetics were determined for the UGT with the most intense glucuronide peak. Six imidazole antifungals, three triazoles, and the benzodiazepine alprazolam (triazole) were evaluated in this study. All compounds investigated were identified as substrates of UGT. UGT1A4 was the main enzyme involved in the metabolism of all compounds except for fluconazole, which was mainly metabolized by UGT2B7, probably mediating its O-glucuronide metabolism. UGT1A3 was also found to be involved in the metabolism of all imidazoles but not triazoles. In both HLM and rUGT K(m) values were lower for imidazoles (14.8-144 microM) than for triazoles (158-3037 microM), with the exception of itraconazole (8.4 microM). All of the imidazoles studied inhibited their own metabolism at high substrate concentrations. In terms of UGT1A4 metabolism, itraconazole showed kinetic features characteristic of imidazole rather than triazole antifungals. This behavior is attributed to the physicochemical properties of itraconazole that are similar to those of imidazoles in terms of clogP. PMID- 20304966 TI - Spironolactone and canrenone inhibit UGT2B7-catalyzed human liver and kidney microsomal aldosterone 18beta-glucuronidation: a potential drug interaction. AB - Elevated plasma concentrations of aldosterone (ALDO) are observed in patients treated with spironolactone. Because ALDO is eliminated via UGT2B7-catalyzed 18beta-glucuronidation, this study aimed to determine whether spironolactone and its primary metabolites, canrenone and canrenoic acid, inhibit ALDO 18beta glucuronidation by recombinant UGT2B7 and by human liver (HLM) and human kidney cortical (HKCM) microsomes. Initial experiments characterized the effects of all three compounds on 4-methylumbelliferone and ALDO glucuronidation by recombinant human UGT2B7. IC(50) values for spironolactone and canrenone ranged from 26 to 50 microM, whereas canrenoic acid was a weak inhibitor. Inhibitor constant (K(i)) values for spironolactone and canrenone inhibition of ALDO 18beta-glucuronidation were subsequently determined with HLM, HKCM, and UGT2B7 as the enzyme sources. Spironolactone and canrenone were competitive inhibitors of ALDO 18beta glucuronidation by HLM, HKCM, and UGT2B7. Mean (+/-) K(i) values for spironolactone were 52 +/- 22 (HLM) and 34 +/- 4 microM (HKCM), and mean (+/-) K(i) values for canrenone were 41 +/- 19 (HLM) and 23 +/- 2 microM (HKCM). K(i) values for spironolactone and canrenone inhibition of ALDO 18beta-glucuronidation by recombinant UGT2B7 were 23 and 11 microM, respectively. "Actual" K(i) values for spironolactone and canrenone inhibition of ALDO 18beta-glucuronidation, which take into account the role of endogenous microsomal inhibitors, are predicted to be 3 to 5 and 2 to 4 microM, respectively. The data indicate that the elevated ALDO concentrations observed in patients treated with spironolactone may be due, at least in part, to a pharmacokinetic interaction, and spironolactone and canrenone should be considered to be potential inhibitors of the UGT2B7-mediated metabolic clearance of drugs in both liver and kidney. PMID- 20304967 TI - Innovative virtual reality measurements for embryonic growth and development. AB - BACKGROUND: Innovative imaging techniques, using up-to-date ultrasonic equipment, necessitate specific biometry. The aim of our study was to test the possibility of detailed human embryonic biometry using a virtual reality (VR) technique. METHODS: In a longitudinal study, three-dimensional (3D) measurements were performed from 6 to 14 weeks gestational age in 32 pregnancies (n = 16 spontaneous conception, n = 16 IVF/ICSI). A total of 125 3D volumes were analysed in the I-Space VR system, which allows binocular depth perception, providing a realistic 3D illusion. Crown-rump length (CRL), biparietal diameter (BPD), occipito-frontal diameter (OFD), head circumference (HC) and abdominal circumference (AC) were measured as well as arm length, shoulder width, elbow width, hip width and knee width. RESULTS: CRL, BPD, OFD and HC could be measured in more than 96% of patients, and AC in 78%. Shoulder width, elbow width, hip width and knee width could be measured in more than 95% of cases, and arm length in 82% of cases. Growth curves were constructed for all variables. Ear and foot measurements were only possible beyond 9 weeks gestation. CONCLUSIONS: This study provides a detailed, longitudinal description of normal human embryonic growth, facilitated by a VR system. Growth curves were created for embryonic biometry of the CRL, BPD, HC and AC early in pregnancy and also of several 'new' biometric measurements. Applying virtual embryoscopy will enable us to diagnose growth and/or developmental delay earlier and more accurately. This is especially important for pregnancies at risk of severe complications, such as recurrent late miscarriage and early growth restriction. PMID- 20304968 TI - Functional cyanobacterial beta-carboxysomes have an absolute requirement for both long and short forms of the CcmM protein. AB - Carboxysomes are an essential part of the cyanobacterial CO2-concentrating mechanism, consisting of a protein shell and an interior of Rubisco. The beta carboxysome shell protein CcmM forms two peptides via a proposed internal ribosomal entry site (IRES) within the ccmM transcript in Synechococcus PCC7942. The abundant short form (35 kD, M35) consists of Rubisco small subunit-like repeats and binds Rubisco. The lower abundance long form (58 kD, M58) also contains a gamma-carbonic anhydrase-like domain, which binds the carboxysomal carbonic anhydrase, CcaA. We examined whether these CcmM forms arise via an IRES or by other means. Mutations of a putative internal start codon (GTG) and Shine Dalgarno sequence within ccmM, along with a gene coding for M35 alone, were examined in the high-CO2-requiring (HCR) carboxysomeless mutant, DeltaccmM. Expression of wild-type ccmM in DeltaccmM restored the wild-type phenotype, while mutation of putative start and Shine-Dalgarno sequences led to as much as 20-fold reduction in M35 content with no recovery from HCR phenotype. These cells also contained small electron-dense structures. Cells producing little or no M58, but sufficient M35, were found to contain large electron-dense structures, no CcaA, and had a HCR phenotype. Large subcellular aggregates can therefore form in the absence of M58, suggesting a role for M35 in internal carboxysome Rubisco packing. The results confirm that M35 is independently translated via an IRES within ccmM. Importantly, the data reveal that functional carboxysomes require both M35 and M58 in sufficient quantities and with a minimum stoichiometry of close to 1:1. PMID- 20304969 TI - Significance of light, sugar, and amino acid supply for diurnal gene regulation in developing barley caryopses. AB - The caryopses of barley (Hordeum vulgare), as of all cereals, are complex sink organs optimized for starch accumulation and embryo development. While their early to late development has been studied in great detail, processes underlying the caryopses' diurnal adaptation to changes in light, temperature, and the fluctuations in phloem-supplied carbon and nitrogen have remained unknown. In an attempt to identify diurnally affected processes in developing caryopses at the early maturation phase, we monitored global changes of both gene expression and metabolite levels. We applied the 22 K Barley1 GeneChip microarray and identified 2,091 differentially expressed (DE) genes that were assigned to six major diurnal expression clusters. Principal component analysis and other global analyses demonstrated that the variability within the data set relates to genes involved in circadian regulation, storage compound accumulation, embryo development, response to abiotic stress, and photosynthesis. The correlation of amino acid and sugar profiles with expression trajectories led to the identification of several hundred potentially metabolite-regulated DE genes. A comparative analysis of our data set and publicly available microarray data disclosed suborgan-specific expression of almost all diurnal DE genes, with more than 350 genes specifically expressed in the pericarp, endosperm, or embryo tissues. Our data reveal a tight linkage between day/night cycles, changes in light, and the supply of carbon and nitrogen. We present a model that suggests several phases of diurnal gene expression in developing barley caryopses, summarized as starvation and priming, energy collection and carbon fixation, light protection and chaperone activity, storage and growth, and embryo development. PMID- 20304970 TI - Tools for cellulose analysis in plant cell walls. PMID- 20304971 TI - Cytosolic action of phytochelatin synthase. AB - Glutathionylation of compounds is an important reaction in the detoxification of electrophilic xenobiotics and in the biosynthesis of endogenous molecules. The glutathione conjugates (GS conjugates) are further processed by peptidic cleavage reactions. In animals and plants, gamma-glutamyl transpeptidases initiate the turnover by removal of the glutamate residue from the conjugate. Plants have a second route leading to the formation of gamma-glutamylcysteinyl (gamma-GluCys) conjugates. Phytochelatin synthase (PCS) is well known to mediate the synthesis of heavy metal-binding phytochelatins. In addition, the enzyme is also able to catabolize GS conjugates to the gamma-GluCys derivative. In this study, we addressed the cellular compartmentalization of PCS and its role in the plant specific gamma-GluCys conjugate pathway in Arabidopsis (Arabidopsis thaliana). Localization studies of both Arabidopsis PCS revealed a ubiquitous presence of AtPCS1 in Arabidopsis seedlings, while AtPCS2 was only detected in the root tip. A functional AtPCS1:eGFP (enhanced green fluorescent protein) fusion protein was localized to the cytosolic compartment. Inhibition of the vacuolar import of GS bimane conjugate via azide treatment resulted in both a strong accumulation of gamma-GluCys-bimane and a massive increase of the cellular cysteine to GS-bimane ratio, which was not observed in PCS-deficient lines. These findings support a cytosolic action of PCS. Analysis of a triple mutant deficient in both Arabidopsis PCS and vacuolar gamma-glutamyl transpeptidase GGT4 is consistent with earlier observations of an efficient sequestration of GS conjugates into the vacuole and the requirement of GGT4 for their turnover. Hence, PCS contributes specifically to the cytosolic turnover of GS conjugates, and AtPCS1 plays the prominent role. We discuss a potential function of PCS in the cytosolic turnover of GS conjugates. PMID- 20304972 TI - Improving thermostability of papain through structure-based protein engineering. AB - Papain is a plant cysteine protease of industrial importance having a two-domain structure with its catalytic cleft located at the domain interface. A structure based rational design approach has been used to improve the thermostability of papain, without perturbing its enzymatic activity, by introducing three mutations at its interdomain region. A thermostable homologue in papain family, Ervatamin C, has been used as a template for this purpose. A single (K174R), a double (K174RV32S) and a triple (K174RV32SG36S) mutant of papain have been generated, of which the triple mutant shows maximum thermostability with the half-life (t(1/2)) extended by 94 min at 60 degrees C and 45 min at 65 degrees C compared to the wild type (WT). The temperature of maximum enzymatic activity (T(max)) and 50% maximal activity (T(50)) for the triple mutant increased by 15 and 4 degrees C, respectively. Moreover, the triple mutant exhibits a faster inactivation rate beyond T(max) which may be a desirable feature for an industrial enzyme. The values of t(1/2) and T(max) for the double mutant lie between those of the WT and the triple mutant. The single mutant however turns out to be unstable for biochemical characterization. These results have been substantiated by molecular modeling studies which also indicate highest stability for the triple mutant based on higher number of interdomain H-bonds/salt-bridges, less interdomain flexibility and lower stability free-energy compared to the WT. In silico studies also explain the unstable behavior of the single mutant. PMID- 20304973 TI - Creating novel proteins by combining design and selection. AB - We present the results of combining design and selection to remodel a protein peptide binding interface, using the peptide PTIEEVD and the TPR1 module interaction as our test case. We initially used the program Rosetta to interrogate possible TPR1 sequences compatible with binding the peptide PTIEEVD. Based on these results, we screened a small library of TPR1 variants, using a split GFP fluorescent assay to identify proteins that are able to bind to the PTIEEVD peptide. We discuss the similarities and differences between the modeling and selection results at each position. We show that a new 'consensus' TPR1, created based on the results of the sequences identified in the screen, indeed binds to the PTIEEVD peptide. These results demonstrate the utility of combining design and selection in a synergistic fashion to remodel protein recognition interfaces. PMID- 20304974 TI - Use of amino acid composition to predict epitope residues of individual antibodies. AB - We identified specific amino acid propensities at the interfaces of antigen antibody interactions in non-redundant qualified antigen-antibody complex structures from Protein Data Bank. Propensities were expressed by the frequency of each of the 20 x 20 standard amino acid pairs that appeared at the interfaces of the complexes and were named the antibody-specific epitope propensity (ASEP) index. Using this index, we developed a novel method of predicting epitope residues for individual antibodies by narrowing down candidate epitope residues which was predicted by the conventional method. The 74 benchmarked antigens were used in ASEP prediction. The efficiency of this method was assessed using the leave-one-out approach. On elimination of residues with ASEP indices in the lowest 10% of all measured, true positives were enriched for 49 antigens. On subsequent elimination of residues with ASEP indices in the lowest 50%, true positives were enriched for 40 of the 74 antigens assessed. The ASEP index is the first benchmark proposed to predict epitope residues for an individual antibody. Used in combination with mutation experiments, this index has the potential to markedly increase the success ratio of epitope analysis. PMID- 20304975 TI - Natural and synthetic compounds such as trimethoprim behave as inhibitors of efflux in Gram-negative bacteria. AB - OBJECTIVES: We hypothesized that small heterocyclic or nitrogen-containing compounds could act as RND efflux pump inhibitors (EPIs). To ascertain possible EPIs, we sought to identify compounds that synergized with substrates of RND efflux pumps for wild-type bacteria and those that overexpress an efflux pump, but had no synergistic activity against strains in which a gene encoding a component of the AcrAB-TolC efflux pump had been inactivated. METHODS: Twenty-six compounds plus L-phenylalanyl-L-arginyl-beta-naphthylamide (PAbetaN) and carbonyl cyanide m-chlorophenylhydrazone (CCCP) were screened by bioassay to identify compounds that synergized with ciprofloxacin for a range of Enterobacteriaceae and Pseudomonas aeruginosa. The MICs of ciprofloxacin, tetracycline, chloramphenicol, erythromycin and ethidium bromide+/-synergizing compounds were determined, and the ability to inhibit the efflux of Hoechst 33342 was measured. RESULTS: Two compounds, trimethoprim and epinephrine, consistently showed synergy with antibiotics for most strains. The combinations did not show synergy for Salmonella enterica serovar Typhimurium in which the AcrAB-TolC efflux pump was inactive. Both compounds inhibited the efflux of Hoechst 33342. CONCLUSIONS: Two compounds, trimethoprim and epinephrine, which are already licensed for use in man, may warrant further analysis as EPIs. The combination of trimethoprim with another antibiotic is a well-used combination in anti-infective chemotherapy, and so combination with another agent, such as a quinolone, may be a viable option and further studies are now required. PMID- 20304976 TI - A field test of the effects of instruction design on colorectal cancer self screening accuracy. AB - A field experiment tested whether instruction design improves accurate adherence to instructions for medical do-it-yourself tests like the Fecal Occult Blood Test (FOBT). As part of an outreach campaign, 16,073 participants received FOBTs with instructions that were (i) human factored, (ii) motivational, (iii) human factored/motivational combined, or (iv) the standard used in the past. Among all test results returned (N = 2483), only the human factors instructions reduced errors in filling out result cards. However, after post-validating result cards that had errors, the human-factored, motivational and merged instructions reduced errors. The present findings show that medical instructions designed with human factors and persuasion principles increase accurate adherence. These design principles provide simple and cost-effective ways to increase test taking accuracy and FOBT effectiveness. Better screening instructions can improve the chances of detecting colorectal cancer early, which may help to decrease cancer mortality. PMID- 20304977 TI - A new approach for copy number estimation in polyploids. AB - In polyploids, the copy number (or marker dosage) of a dominant marker is the number of copies of a dominant allele carried by a parent. It is estimated using a hypothesis testing procedure. This procedure, however, suffers from issues associated with multiple testing and assumes all chromosomes pair uniformly. In this paper, a new Bayesian approach is presented for estimating the copy number of a dominant marker in polyploids. By using a probability model that explicitly accounts for preferentially paired chromosomes, the Bayesian approach more closely reflects reality. Its superiority over the hypothesis testing procedure is evidenced through the analysis of simulated and sugarcane data. The Bayesian methodology described in this paper is implemented in a C program, bdose, which is freely available (see Supplementary Materials). PMID- 20304978 TI - Inhibition of 3-hydroxy-3-methylglutaryl-coenzyme A reductase activity and of Ras farnesylation mediate antitumor effects of anandamide in human breast cancer cells. AB - The endocannabinoid system regulates cell proliferation in human breast cancer cells. Recently, we described that a metabolically stable anandamide analog, 2 methyl-2'-F-anandamide, by activation of CB1 receptors significantly inhibited cell proliferation of human breast cancer cell lines. In this study, we observed that the activation of the CB1 receptor, in two human mammary carcinoma cell lines, MDA-MB-231 and MCF7, caused the inhibition of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase activity due to a reduction of HMG-CoA reductase transcript levels. The decrease of HMG-CoA reductase activity induced the inhibition of the prenylation of proteins, in particular of the farnesylation of Ras oncogenic protein involved in cell proliferation of these cell lines. We suggest that the inhibitory effect of anandamide analog on tumor cell proliferation could be related to the inhibition of Ras farnesylation. PMID- 20304980 TI - Effect on postoperative sore throat of spraying the endotracheal tube cuff with benzydamine hydrochloride, 10% lidocaine, and 2% lidocaine. AB - BACKGROUND: Postoperative sore throat (POST) is a common complication after endotracheal intubation. We compared the effectiveness on POST of spraying the endotracheal tube (ETT) cuff with benzydamine hydrochloride, 10% lidocaine, and 2% lidocaine. METHODS: Three hundred seventy-two patients were randomly allocated into 4 groups. The ETT cuffs in each group were sprayed with benzydamine hydrochloride, 10% lidocaine hydrochloride, 2% lidocaine hydrochloride, or normal saline before endotracheal intubation. After insertion, the cuffs were inflated to an airway leak pressure of 20 cm H(2)O. Anesthesia was maintained with propofol. The patients were examined for sore throat (none, mild, moderate, or severe) at 1, 6, 12, and 24 hours after extubation. RESULTS: The highest incidence of POST occurred at 6 hours after extubation in all groups. There was a significantly lower incidence of POST in the benzydamine group than 10% lidocaine, 2% lidocaine, and normal saline groups (P < 0.05) at each observation time point. At 6 hours after extubation, the incidence of POST was significantly lower in the benzydamine group (17.0%) compared with 10% lidocaine (53.7%), 2% lidocaine (37.0%), and normal saline (40.8%) groups (P < 0.05). The benzydamine group had significantly decreased severity of POST compared with the 10% lidocaine, 2% lidocaine, and normal saline groups (P < 0.05) at each observation time point. Compared with the 2% lidocaine and normal saline groups, the 10% lidocaine group had significantly increased severity of POST at 1, 6, and 12 hours after extubation. There were no significant differences among groups in local or systemic side effects. CONCLUSIONS: Spraying benzydamine hydrochloride on the ETT cuff is a simple and effective method to reduce the incidence and severity of POST. PMID- 20304979 TI - Defective nucleolar localization and dominant interfering properties of a parafibromin L95P missense mutant causing the hyperparathyroidism-jaw tumor syndrome. AB - The hyperparathyroidism-jaw tumor syndrome (HPT-JT) is a familial cancer syndrome that can result from germline inactivation of HRPT2/CDC73, a putative tumor suppressor gene that encodes parafibromin, a component of the transcriptional regulatory PAF1 complex with homology to the yeast protein Cdc73p. The vast majority of HRPT2/CDC73 germline mutations identified have been truncation or frameshift mutations, and loss of function due to missense mutation is rare. We report here a kindred with HPT-JT due to a germline L95P missense mutation in parafibromin. The mutant parafibromin was studied in vitro to understand the basis of its presumed loss-of-function. When transfected in cultured cells, the L95P mutant was expressed to a lower level than wild-type (wt) parafibromin, a difference that was not overcome by inhibition of the proteasomal degradation pathway. The L95P mutant parafibromin retained the ability to assemble with endogenous PAF1 complex components as evidenced by co-immunoprecipitation. Analysis of subcellular localization showed that the L95P mutant was markedly deficient in nucleolar localization compared to the wt, an impairment likely resulting from disruption of a putative nucleolar localization signal immediately upstream of the L95P mutation. Transfection of the L95P parafibromin mutant, but not the wt, enhanced cell cycle progression and increased cell survival in NIH 3T3 and HEK 293 cells, resulting apparently from dominant interference with endogenous parafibromin action. The simultaneous loss of nucleolar localization and acquisition of a growth stimulatory phenotype with the L95P mutation raise the possibility that parafibromin must interact with targets in the nucleolus to fully execute its tumor suppressor functions. PMID- 20304981 TI - The effect of sex on the minimum local analgesic concentration of ropivacaine for caudal anesthesia in anorectal surgery. AB - BACKGROUND: Caudal anesthesia is routinely used in our hospital for most of ambulatory anorectal surgery; patients need to recover as quickly as possible. The dose of local anesthetic may be different for male and female patients. We designed this study to investigate the effect of sex on the minimum local anesthetic concentration (MLAC) of ropivacaine for caudal anesthesia. METHODS: In this double-blind, prospective study, we enrolled 70 ASA physical status I patients (35 male and 35 female) who were scheduled for anorectal surgery under caudal anesthesia, and allocated them to 2 study groups according to their gender. Each participant received a single injection of 20 mL ropivacaine through a caudal catheter. Using Dixon's up-and-down sequential allocation, the first participant received 0.2% and subsequent concentrations were determined by the analgesic response of the previous patients to the initial skin incision and laxity of the anal sphincter. The concentration change was 0.025%. The up-and down sequences were analyzed using the Dixon and Massey method to quantify the caudal analgesic block effective concentrations in 50% of patients. RESULTS: The MLAC of ropivacaine for caudal analgesia was 0.296% (95% confidence interval, 0.286%-0.307%) in male patients and 0.389% (95% confidence interval, 0.372% 0.407%) in female patients (P < 0.01). CONCLUSIONS: We conclude that the ropivacaine MLAC for caudal anesthesia in female patients is 31% larger than in male patients. PMID- 20304982 TI - Levobupivacaine 0.5% provides longer analgesia after sciatic nerve block using the Labat approach than the same dose of ropivacaine in foot and ankle surgery. AB - BACKGROUND: Levobupivacaine and ropivacaine are 2 left enantiomeric molecules frequently used for peripheral nerve blocks because of their safe clinical profile. Levobupivacaine is more lipophilic and theoretically more potent than ropivacaine, but clinical studies show conflicting results in terms of anesthetic and analgesic characteristics. We hypothesized that the pure S-enantiomer of bupivacaine provides longer-lasting analgesia than ropivacaine. METHODS: We compared the analgesic characteristics of 20 mL levobupivacaine versus 20 mL ropivacaine 0.5% in a posterior sciatic nerve block (Labat approach) for foot and ankle surgery. In a double-blind, randomized, prospective design, 80 patients received either substance. We assessed the onset, duration, and success of the block, and the need for rescue analgesia and technical or neurologic complications over 24 hours. RESULTS: The onset of sensory block (minutes) and the success rate were similar in levobupivacaine and ropivacaine groups (onset, 15 minutes [5-40 minutes] vs 15 minutes [5-60 minutes], respectively; success rate, 90% vs 92.5%). The average time for the first request of pain medication provided by 20 mL levobupivacaine 0.5% was significantly longer than with ropivacaine (1605 minutes [575-2400 minutes] vs 1035 minutes [590-1500 minutes], P < 0.001). The need for postoperative rescue analgesia was higher in the ropivacaine group (37 of 40 [92.5%] vs 30 of 40 [75%], P < 0.034). No complications were noted in either group at 24 hours. CONCLUSION: Twenty milliliters levobupivacaine 0.5% in posterior gluteal (Labat) sciatic nerve block provided longer-lasting analgesia after foot and ankle surgery compared with the same dose of ropivacaine. PMID- 20304983 TI - Neurogenic bladder: a complication after endoscopic adhesiolysis with return of bladder function while using nitrofurantoin. AB - We describe the case of a 73-year-old woman with a history of chronic low back pain and 2 previous lumbar fusions who presented with complaints of worsening back and leg pain. Having previously undergone multiple interventions, physical therapy, and oral analgesics with limited pain relief, the patient opted for endoscopic lysis of adhesions for severe scarring of the epidural space. Subsequently, the patient developed a neurogenic bladder with urinary retention. Three years later, she experienced resolution of the neurogenic bladder symptoms that coincided with the use of the antibiotic nitrofurantoin. Upon discontinuation of the antibiotic, the patient noted that she was unable to void spontaneously. With reinstitution of nitrofurantoin, the patient was once again able to void effectively and has been maintained on nitrofurantoin for >3 years. PMID- 20304984 TI - Nicotinic acetylcholine receptor gene expression is altered in burn patients. AB - INTRODUCTION: Burn patients have been observed to be more susceptible to the hyperkalemic effect of the depolarizing muscle relaxant succinylcholine. Changes in nicotinic acetylcholine receptor (nAChR) subunit composition may alter electrophysiologic, pharmacologic, and metabolic characteristics of the receptor inducing hyperkalemia on exposure to succinylcholine. No studies have been performed that show the upregulation and/or alteration of nAChR subunit composition in human burn patients. The scarcity of studies performed on humans with burn injury is mainly attributable to the technical and ethical difficulties in obtaining muscle biopsies at different time frames of illness in these acutely injured patients. nAChRs are expressed in oral keratinocytes and are upregulated or altered in smokers. However, no studies have addressed the expression of nAChRs in the oral mucosa of burn patients. METHODS: Buccal mucosal scrapings were collected from 9 burn patients and 6 control nonburn surgical intensive care unit patients. For burn and control patients, tissues were collected upon presentation (time: 0 hour) and at time points 12, 24, and 48 hours, 1 week, and 2 weeks. Gene expression of the nAChR subunits alpha1, alpha7, gamma, and epsilon were performed using real-time reverse transcriptase polymerase chain reaction. RESULTS: alpha7 and gamma nAChR genes were significantly upregulated in burn patients, whereas alpha1 and epsilon nAChR genes were minimally affected, showing no significant changes over time. DISCUSSION: Over the 2 weeks of measurement, an upregulation of the alpha7 and gamma genes occurred in both burn and control patients; however, the proportion of alpha7 and gamma subunit increases was significantly higher in burn patients than in control surgical intensive care unit patients. The relationship between the thermal injury and the observed alteration in gene expression suggests a possible cause/effect relationship. This effect was observed at a site not affected by the burn injury and in nonmuscle tissues, thus emphasizing the systemic nature of the effect caused by the thermal injury. Because gene expression is the basis of protein production, the upregulation of alpha7 and gamma genes might translate into more alpha7 and gamma protein subunits. These proteins can also combine with each other or with other types of subunits (alpha1, beta, epsilon . . .) to form nAChRs with altered electrophysiologic characteristics leading to the observed abnormal clinical outcomes. CONCLUSION: Thermal injury may infer a systemic effect because upregulation/alteration of nAChRs occurs in nonmuscle tissues distant from the site of injury. The effect of thermal injury on nAChR gene subunits can be studied using a minimally invasive method (buccal mucosal scraping) and a highly sensitive technology (real-time reverse transcriptase polymerase chain reaction) obviating the need for more invasive methods. PMID- 20304985 TI - The anatomy of the thoracic spinal canal investigated with magnetic resonance imaging. AB - BACKGROUND: We investigated, with magnetic resonance imaging, the distance of the dura mater to the spinal cord in patients without spinal or medullar disease at the 2nd, 5th, and 10th thoracic segments. METHODS: Fifty patients in the supine position underwent magnetic resonance imaging. Medial sagittal slices of the 2nd, 5th, and 10th thoracic segments were measured for the relative distances using the 1.5-T superconducting system (Gyroscan Intera, Philips Medical Systems, Best, the Netherlands). In 10 patients, the angles relative to the tangent at the insertion point on the skin were measured. RESULTS: The posterior dural-spinal cord distance is significantly greater at the midthoracic region (5th thoracic = 5.8 +/- 0.8 mm) than at the upper (2nd thoracic = 3.9 +/- 0.8 mm) and lower thoracic levels (10th thoracic = 4.1 +/- 1.0 mm) (P < 0.015). There were no differences between interspaces T2 and T10. There was no correlation between age and the measured distance between the dura mater and the spinal cord. The entry angle of the needle at T2 was 9.0 degrees +/- 2.5 degrees ; at T5, 45.0 degrees +/- 7.4 degrees ; and at T10, 9.5 degrees +/- 4.2 degrees . CONCLUSIONS: This study demonstrated that there is greater depth of the posterior subarachnoid space at the T2, T5, and T10 levels. The greater distance was found at T5. PMID- 20304986 TI - The effects of isoflurane pretreatment on cerebral blood flow, capillary permeability, and oxygen consumption in focal cerebral ischemia in rats. AB - BACKGROUND: We performed experiments to test whether isoflurane pretreatment produces vascular effects, especially at the levels of arterioles and capillaries affecting regional cerebral blood flow (rCBF), O(2) supply and consumption, or capillary permeability in focal cerebral ischemia. Because inducible nitric oxide synthase (iNOS) was implicated as one of the mechanisms of isoflurane preconditioning, the effect of iNOS inhibition on rCBF was also studied. METHODS: Twenty-four hours before middle cerebral artery (MCA) occlusion, rats were pretreated with 2% isoflurane for 30 minutes using an endotracheal tube and mechanical ventilation for the isoflurane preconditioned (IsoPC) group. For the group of iNOS inhibition, aminoguanidine 200 mg/kg was injected IP 30 minutes before isoflurane pretreatment. One hour after MCA occlusion, rCBF was measured using (14)C-iodoantipyrine autoradiography. Alternate slices of the tissue were used to determine arteriolar and venular O(2) saturation using cryo microspectrophotometry. Capillary permeability was determined by measuring the transfer coefficient (Ki) of (14)C-alpha-aminoisobutyric acid. Additional measurements of rCBF were performed at 3 hours after MCA occlusion. RESULTS: MCA occlusion decreased rCBF and O(2) consumption and increased Ki in both the control and the IsoPC groups at 1 hour after MCA occlusion. In the ischemic cortex (IC), the rCBF and O(2) consumption were significantly greater in the IsoPC group than in the control group (+40% and +41%, respectively), but they were similar in the contralateral cortex between the 2 groups. There was no difference in Ki between the groups in the IC or in the contralateral cortex. The increase of rCBF in the IC (+50%) was sustained in the IsoPC group at 3 hours after MCA occlusion. With iNOS inhibition, the increase of rCBF in the IC with isoflurane pretreatment became insignificant. CONCLUSIONS: Our data demonstrate that isoflurane pretreatment improved rCBF and increased the regional O(2) supply and consumption in the focal ischemic area but did not affect capillary permeability during the early stage of focal cerebral ischemia. The isoflurane induced increase in rCBF in the ischemic area became insignificant with inhibition of iNOS. PMID- 20304987 TI - Ergosterol triggers characteristic elicitation steps in Beta vulgaris leaf tissues. AB - This study investigates the role of the fungal sterol ergosterol as a general elicitor in the triggering of plant innate immunity in sugar beet. Evidence for this specific function of ergosterol is provided by careful comparison with cholesterol and three plant sterols (stigmasterol, campesterol, sitosterol), which do not enable the integrity of responses leading to elicitation. Our results demonstrate the modification of H(+) flux by ergosterol, due to the direct inhibition of the H(+)-ATPase activity on plasma membrane vesicles purified from leaves. The ergosterol-induced oxidative burst is related to enhanced NADPH-oxidase and superoxide dismutase activities. The similar effects obtained with the fungal elicitor chitosan further reinforce the particular role of ergosterol in the induced defences. The involvement of salicylic acid and/or jasmonic acid signalling in the ergosterol-enhanced plant non-host resistance is also studied. The possible link between ergosterol-triggered plant innate immunity and its putative impact on the structural organization of plant plasma membrane are discussed in terms of the ability of this fungal sterol to promote the formation of lipid rafts. PMID- 20304988 TI - Differential regulation of the multiple flagellins in spirochetes. AB - The expression of flagellin genes in most bacteria is typically regulated by the flagellum-specific sigma(28) factor FliA, and an anti-sigma(28) factor, FlgM. However, the regulatory hierarchy in several bacteria that have multiple flagellins is more complex. In these bacteria, the flagellin genes are often transcribed by at least two different sigma factors. The flagellar filament in spirochetes consists of one to three FlaB core proteins and at least one FlaA sheath protein. Here, the genetically amenable bacterium Brachyspira hyodysenteriae was used as a model spirochete to investigate the regulation of its four flagellin genes, flaA, flaB1, flaB2, and flaB3. We found that the flaB1 and flaB2 genes are regulated by sigma(28), whereas the flaA and flaB3 genes are controlled by sigma(70). The analysis of a flagellar motor switch fliG mutant further supported this proposition; in the mutant, the transcription of flaB1 and flaB2 was inhibited, but that of flaA and flaB3 was not. In addition, the continued expression of flaA and flaB3 in the mutant resulted in the formation of incomplete flagellar filaments that were hollow tubes and consisted primarily of FlaA. Finally, our recent studies have shown that each flagellin unit contributes to the stiffness of the periplasmic flagella, and this stiffness directly correlates with motility. The regulatory mechanism identified here should allow spirochetes to change the relative ratio of these flagellin proteins and, concomitantly, vary the stiffness of their flagellar filament. PMID- 20304989 TI - The actinomycin biosynthetic gene cluster of Streptomyces chrysomallus: a genetic hall of mirrors for synthesis of a molecule with mirror symmetry. AB - A gene cluster was identified which contains genes involved in the biosynthesis of actinomycin encompassing 50 kb of contiguous DNA on the chromosome of Streptomyces chrysomallus. It contains 28 genes with biosynthetic functions and is bordered on both sides by IS elements. Unprecedentedly, the cluster consists of two large inverted repeats of 11 and 13 genes, respectively, with four nonribosomal peptide synthetase genes in the middle. Nine genes in each repeat have counterparts in the other, in the same arrangement but in the opposite orientation, suggesting an inverse duplication of one of the arms during the evolution of the gene cluster. All of the genes appear to be organized into operons, each corresponding to a functional section of actinomycin biosynthesis, such as peptide assembly, regulation, resistance, and biosynthesis of the precursor of the actinomycin chromophore 4-methyl-3-hydroxyanthranilic acid (4 MHA). For 4-MHA synthesis, functional analysis revealed genes that encode pathway specific isoforms of tryptophan dioxygenase, kynurenine formamidase, and hydroxykynureninase, which are distinct from the corresponding enzyme activities of cellular tryptophan catabolism in their regulation and in part in their substrate specificity. Phylogenetic analysis indicates that the pathway-specific tryptophan metabolism in Streptomyces most probably evolved divergently from the normal pathway of tryptophan catabolism to provide an extra or independent supply of building blocks for the synthesis of tryptophan-derived secondary metabolites. PMID- 20304990 TI - Characterization of the Pseudomonas aeruginosa transcriptional response to phenylalanine and tyrosine. AB - Pseudomonas aeruginosa is a Gram-negative opportunistic pathogen often associated with chronic infections in the lungs of individuals with the heritable disease cystic fibrosis (CF). Previous work from our laboratory demonstrated that aromatic amino acids within CF lung secretions (sputum) not only serve as carbon and energy sources but also enhance synthesis of the cell signaling molecule Pseudomonas quinolone signal (PQS). The present study investigates the role of the aromatic amino acid-responsive regulator PhhR in mediating these phenotypes. Transcriptome analysis revealed that PhhR controls four putative transcriptional units (phhA, hpd, hmgA, and dhcA) involved in aromatic amino acid catabolism; however, genes involved in PQS biosynthesis were unaffected. The phhA, hpd, hmgA, and dhcA promoters were mapped by primer extension, and purified His(6)-PhhR was shown to bind the phhA, hpd, and dhcA promoters in vitro by use of electrophoretic mobility shift assays. Our work characterizes a transcriptional regulator of catabolic genes induced during P. aeruginosa growth in CF sputum. PMID- 20304991 TI - GlnB/GlnK PII proteins and regulation of the Sinorhizobium meliloti Rm1021 nitrogen stress response and symbiotic function. AB - The Sinorhizobium meliloti Rm1021 Delta glnD-sm2 mutant, which is predicted to make a GlnD nitrogen sensor protein truncated at its amino terminus, fixes nitrogen in symbiosis with alfalfa, but the plants cannot use this nitrogen for growth (S. N. Yurgel and M. L. Kahn, Proc. Natl. Acad. Sci. U. S. A. 105:18958 18963, 2008). The mutant also has a generalized nitrogen stress response (NSR) defect. These results suggest a connection between GlnD, symbiotic metabolism, and the NSR, but the nature of this connection is unknown. In many bacteria, GlnD modifies the PII proteins, GlnB and GlnK, as it transduces a measurement of bacterial nitrogen status to a cellular response. We have now constructed and analyzed Rm1021 mutants missing GlnB, GlnK, or both proteins. Rm1021 Delta glnK Delta glnB was much more defective in its NSR than either single mutant, suggesting that GlnB and GlnK overlap in regulating the NSR in free-living Rm1021. The single mutants and the double mutant all formed an effective symbiosis, indicating that symbiotic nitrogen exchange could occur without the need for either GlnB or GlnK. N-terminal truncation of the GlnD protein interfered with PII protein modification in vitro, suggesting either that unmodified PII proteins were responsible for the glnD mutant's ineffective phenotype or that connecting GlnD and appropriate symbiotic behavior does not require the PII proteins. PMID- 20304992 TI - Evidence of localized prophage-host recombination in the lytA gene, encoding the major pneumococcal autolysin. AB - According to a highly polymorphic region in the lytA gene, encoding the major autolysin of Streptococcus pneumoniae, two different families of alleles can be differentiated by PCR and restriction digestion. Here, we provide evidence that this polymorphic region arose from recombination events with homologous genes of pneumococcal temperate phages. PMID- 20304993 TI - Overlapping alternative sigma factor regulons in the response to singlet oxygen in Rhodobacter sphaeroides. AB - Organisms performing photosynthesis in the presence of oxygen have to cope with the formation of highly reactive singlet oxygen ((1)O(2)) and need to mount an adaptive response to photooxidative stress. Here we show that the alternative sigma factors RpoH(I) and RpoH(II) are both involved in the (1)O(2) response and in the heat stress response in Rhodobacter sphaeroides. We propose RpoH(II) to be the major player in the (1)O(2) response, whereas RpoH(I) is more important for the heat stress response. Mapping of the 5' ends of RpoH(II)- and also RpoH(I)/RpoH(II)-dependent transcripts revealed clear differences in the -10 regions of the putative promoter sequences. By using bioinformatic tools, we extended the RpoH(II) regulon, which includes genes induced by (1)O(2) exposure. These genes encode proteins which are, e.g., involved in methionine sulfoxide reduction and in maintaining the quinone pool. Furthermore, we identified small RNAs which depend on RpoH(I) and RpoH(II) and are likely to contribute to the defense against photooxidative stress and heat stress. PMID- 20304994 TI - RecA4142 causes SOS constitutive expression by loading onto reversed replication forks in Escherichia coli K-12. AB - Escherichia coli initiates the SOS response when single-stranded DNA (ssDNA) produced by DNA damage is bound by RecA and forms a RecA-DNA filament. recA SOS constitutive [recA(Con)] mutants induce the SOS response in the absence of DNA damage. It has been proposed that recA(Con) mutants bind to ssDNA at replication forks, although the specific mechanism is unknown. Previously, it had been shown that recA4142(F217Y), a novel recA(Con) mutant, was dependent on RecBCD for its high SOS constitutive [SOS(Con)] expression. This was presumably because RecA4142 was loaded at a double-strand end (DSE) of DNA. Herein, it is shown that recA4142 SOS(Con) expression is additionally dependent on ruvAB (replication fork reversal [RFR] activity only) and recJ (5'-->3' exonuclease), xonA (3'-->5' exonuclease) and partially dependent on recQ (helicase). Lastly, sbcCD mutations (Mre11/Rad50 homolog) in recA4142 strains caused full SOS(Con) expression in an ruvAB-, recBCD , recJ-, and xonA-independent manner. It is hypothesized that RuvAB catalyzes RFR, RecJ and XonA blunt the DSE (created by the RFR), and then RecBCD loads RecA4142 onto this end to produce SOS(Con) expression. In sbcCD mutants, RecA4142 can bind other DNA substrates by itself that are normally degraded by the SbcCD nuclease. PMID- 20304995 TI - Thiol peroxidase protects Salmonella enterica from hydrogen peroxide stress in vitro and facilitates intracellular growth. AB - At present, Salmonella is considered to express two peroxiredoxin-type peroxidases, TsaA and AhpC. Here we describe an additional peroxiredoxin, Tpx, in Salmonella enterica and show that a single tpx mutant is susceptible to exogenous hydrogen peroxide (H(2)O(2)), that it has a reduced capacity to degrade H(2)O(2) compared to the ahpCF and tsaA mutants, and that its growth is affected in activated macrophages. These results suggest that Tpx contributes significantly to the sophisticated defense system that the pathogen has evolved to survive oxidative stress. PMID- 20304996 TI - Identification of a novel estrogen receptor-alpha variant and its upstream splicing regulator. AB - Alternative splicing of precursor mRNA is a fundamental mechanism to generate multiple proteins from a single gene. Although constitutive and alternative mRNA splicing is temporally and spatially regulated, deregulation of mRNA splicing could cause development, progression, and metastasis of tumors. Through yeast two hybrid screening of a human breast cDNA library using estrogen receptor-alpha (ERalpha) as bait, we identified a novel nuclear receptor box containing full length protein, nuclear protein E3-3 (NPE3-3). Our results revealed that NPE3-3 associates with not only ERalpha but also with splicing factors, serine/arginine rich protein (SRp)-30c, SRp40, and splicing factor SC-35, suggesting that NPE3-3 is likely to be involved in regulation of mRNA splicing. Accordingly, transient expression of NPE3-3 in cells resulted in expected splicing of the CD44 control minigene. We also discovered that NPE3-3-overexpressing clones produced a novel, previously unrecognized, alternatively spliced variant of ERalpha (termed ERalphaV), which had a molecular size of 37 kDa composed of only exons 1, 2, 7, and 8. ERalphaV was expressed and sequestered in the cytoplasm in MCF-7 cells stably overexpressing NPE3-3, suggesting its involvement in nongenomic hormone signaling. NPE3-3 clones exhibited up-regulation of ERK1/2 signaling, cyclin D1, and cathepsin D and enhanced tumor cell proliferation, migration, and tumorigenicity. Moreover, direct expression of the ERalphaV in breast cancer cells stimulated ERK1/2 up-regulation and cyclin D1 expression. We found that ERalphaV physically interacted with MAPK kinase (MEK)-1/2, and thus, an ERalphaV and MEK1/2 complex could lead to the activation of the ERK1/2 pathway. Interestingly, NPE3-3 was up-regulated in human breast tumors. These findings revealed a role for NPE3-3 in alternative splicing and suggest that ERalpha is a physiological target of NPE3-3, leading to a constitutive nongenomic signaling pathway in breast cancer cells. PMID- 20304997 TI - Tyrosines 868, 966, and 972 in the kinase domain of JAK2 are autophosphorylated and required for maximal JAK2 kinase activity. AB - Janus kinase 2 (JAK2) is activated by a majority of cytokine family receptors including receptors for GH, leptin, and erythropoietin. To identify novel JAK2 regulatory and/or -binding sites, we set out to identify autophosphorylation sites in the kinase domain of JAK2. Two-dimensional phosphopeptide mapping of in vitro autophosphorylated JAK2 identified tyrosines 868, 966, and 972 as sites of autophosphorylation. Phosphorylated tyrosines 868 and 972 were also identified by mass spectrometry analysis of JAK2 activated by an erythropoietin-bound chimeric erythropoietin receptor/leptin receptor. Phosphospecific antibodies suggest that the phosphorylation of all three tyrosines increases in response to GH. Compared with wild-type JAK2, which is constitutively active when overexpressed, JAK2 lacking tyrosine 868, 966, or 972 has substantially reduced activity. Coexpression with GH receptor and protein tyrosine phosphatase1B allowed us to investigate GH-dependent activation of these mutated JAK2s in human embryonic kidney 293T cells. All three mutated JAK2s are activated by GH, although to a lesser extent than wild-type JAK2. The three mutated JAK2s also mediate GH activation of signal transducer and activator of transcription 3 (Stat3), signal transducer and activator of transcription 5b (Stat5b) and ERK1, but at reduced levels. Coexpression with Src-homology 2B1beta (SH2B1beta), like coexpression with GH-bound GH receptor, partially restores the activity of all three JAK2 mutants. Based on these results and the crystal structure of the JAK2 kinase domain, we hypothesize that small changes in the conformation of the regions of JAK2 surrounding tyrosines 868, 966, and 972 due to e.g. phosphorylation, binding to a ligand-bound cytokine receptor, and/or binding to Src-homology 2B1, may be essential for JAK2 to assume a maximally active conformation. PMID- 20304998 TI - The rules of DNA recognition by the androgen receptor. AB - The androgen receptor (AR) and glucocorticoid, progestagen, and mineralocorticoid receptors all recognize classical DNA response elements that are organized as inverted repeats of 5'-AGAACA-3'-like motifs with a three-nucleotide spacer. Next to such elements, the AR also recognizes a second type of androgen response element (ARE), the so-called selective AREs, which resemble more the direct repeats of the same hexamer. In this work, we show that not only the AR but also the progestagen receptor can recognize the selective AREs, whereas neither glucocorticoid nor mineralocorticoid receptor can. Recently, genomic AR-binding fragments have been postulated to contain AR-binding sites that diverge considerably from the classical ARE consensus. Extensive mutational analyses of these candidate motifs, however, reinstalls the values of the consensus sequence for the AREs as mentioned above, the importance of their dimeric nature and the presence of exactly three-nucleotide spacing. We developed a position-specific probability matrix that was used to predict with higher accuracy new AREs in different AR-binding regions. So far, all AR-binding genomic fragments that were analyzed contain AREs defined as receptor-dimer binding motifs with the ability to confer responsiveness to a reporter gene. PMID- 20304999 TI - Abundant 5S rRNA-like transcripts encoded by the mitochondrial genome in amoebozoa. AB - 5S rRNAs are ubiquitous components of prokaryotic, chloroplast, and eukaryotic cytosolic ribosomes but are apparently absent from mitochondrial ribosomes (mitoribosomes) of many eukaryotic groups including animals and fungi. Nevertheless, a clearly identifiable, mitochondrion-encoded 5S rRNA is present in Acanthamoeba castellanii, a member of Amoebozoa. During a search for additional mitochondrial 5S rRNAs, we detected small abundant RNAs in other members of Amoebozoa, namely, in the lobose amoeba Hartmannella vermiformis and in the myxomycete slime mold Physarum polycephalum. These RNAs are encoded by mitochondrial DNA (mtDNA), cosediment with mitoribosomes in glycerol gradients, and can be folded into a secondary structure similar to that of bona fide 5S rRNAs. Further, in the mtDNA of another slime mold, Didymium nigripes, we identified a region that in sequence, potential secondary structure, and genomic location is similar to the corresponding region encoding the Physarum small RNA. A mtDNA-encoded small RNA previously identified in Dictyostelium discoideum is here shown to share several characteristics with known 5S rRNAs. Again, we detected genes encoding potential homologs of this RNA in the mtDNA of three other species of the genus Dictyostelium as well as in a related genus, Polysphondylium. Taken together, our results indicate a widespread occurrence of small, abundant, mtDNA-encoded RNAs with 5S rRNA-like structures that are associated with the mitoribosome in various amoebozoan taxa. Our working hypothesis is that these novel small abundant RNAs represent radically divergent mitochondrial 5S rRNA homologs. We posit that currently unrecognized 5S-like RNAs may exist in other mitochondrial systems in which a conventional 5S rRNA cannot be identified. PMID- 20305000 TI - Spatial and developmental differentiation of mannitol dehydrogenase and mannitol 1-phosphate dehydrogenase in Aspergillus niger. AB - The presence of a mannitol cycle in fungi has been subject to discussion for many years. Recent studies have found no evidence for the presence of this cycle and its putative role in regenerating NADPH. However, all enzymes of the cycle could be measured in cultures of Aspergillus niger. In this study we have analyzed the localization of two enzymes from the pathway, mannitol dehydrogenase and mannitol 1-phosphate dehydrogenase, and the expression of their encoding genes in nonsporulating and sporulating cultures of A. niger. Northern analysis demonstrated that mpdA was expressed in both sporulating and nonsporulating mycelia, while expression of mtdA was expressed only in sporulating mycelium. More detailed studies using green fluorescent protein and dTomato fused to the promoters of mtdA and mpdA, respectively, demonstrated that expression of mpdA occurs in vegetative hyphae while mtdA expression occurs in conidiospores. Activity assays for MtdA and MpdA confirmed the expression data, indicating that streaming of these proteins is not likely to occur. These results confirm the absence of the putative mannitol cycle in A. niger as two of the enzymes of the cycle are not present in the same part of A. niger colonies. The results also demonstrate the existence of spore-specific genes and enzymes in A. niger. PMID- 20305001 TI - A Plasmodium falciparum transcriptional cyclin-dependent kinase-related kinase with a crucial role in parasite proliferation associates with histone deacetylase activity. AB - Cyclin-dependent protein kinases (CDKs) are key regulators of the eukaryotic cell cycle and of the eukaryotic transcription machinery. Here we report the characterization of Pfcrk-3 (Plasmodium falciparum CDK-related kinase 3; PlasmoDB identifier PFD0740w), an unusually large CDK-related protein whose kinase domain displays maximal homology to those CDKs which, in other eukaryotes, are involved in the control of transcription. The closest enzyme in Saccharomyces cerevisiae is BUR1 (bypass upstream activating sequence requirement 1), known to control gene expression through interaction with chromatin modification enzymes. Consistent with this, immunofluorescence data show that Pfcrk-3 colocalizes with histones. We show that recombinant Pfcrk-3 associates with histone H1 kinase activity in parasite extracts and that this association is detectable even if the catalytic domain of Pfcrk-3 is rendered inactive by site-directed mutagenesis, indicating that Pfcrk-3 is part of a complex that includes other protein kinases. Immunoprecipitates obtained from extracts of transgenic parasites expressing hemagglutinin (HA)-tagged Pfcrk-3 by using an anti-HA antibody displayed both protein kinase and histone deacetylase activities. Reverse genetics data show that the pfcrk-3 locus can be targeted only if the genetic modification does not cause a loss of function. Taken together, our data strongly suggest that Pfcrk-3 fulfils a crucial role in the intraerythrocytic development of P. falciparum, presumably through chromatin modification-dependent regulation of gene expression. PMID- 20305002 TI - Homoserine toxicity in Saccharomyces cerevisiae and Candida albicans homoserine kinase (thr1Delta) mutants. AB - In addition to threonine auxotrophy, mutation of the Saccharomyces cerevisiae threonine biosynthetic genes THR1 (encoding homoserine kinase) and THR4 (encoding threonine synthase) results in a plethora of other phenotypes. We investigated the basis for these other phenotypes and found that they are dependent on the toxic biosynthetic intermediate homoserine. Moreover, homoserine is also toxic for Candida albicans thr1Delta mutants. Since increasing levels of threonine, but not other amino acids, overcome the homoserine toxicity of thr1Delta mutants, homoserine may act as a toxic threonine analog. Homoserine-mediated lethality of thr1Delta mutants is blocked by cycloheximide, consistent with a role for protein synthesis in this lethality. We identified various proteasome and ubiquitin pathway components that either when mutated or present in high copy numbers suppressed the thr1Delta mutant homoserine toxicity. Since the doa4Delta and proteasome mutants identified have reduced ubiquitin- and/or proteasome-mediated proteolysis, the degradation of a particular protein or subset of proteins likely contributes to homoserine toxicity. PMID- 20305003 TI - Fungal homoserine kinase (thr1Delta) mutants are attenuated in virulence and die rapidly upon threonine starvation and serum incubation. AB - The fungally conserved subset of amino acid biosynthetic enzymes not present in humans offer exciting potential as an unexploited class of antifungal drug targets. Since threonine biosynthesis is essential in Cryptococcus neoformans, we further explored the potential of threonine biosynthetic enzymes as antifungal drug targets by determining the survival in mice of Saccharomyces cerevisiae homoserine kinase (thr1Delta) and threonine synthase (thr4Delta) mutants. In striking contrast to aspartate kinase (hom3Delta) mutants, S. cerevisiae thr1Delta and thr4Delta mutants were severely depleted after only 4 h in vivo. Similarly, Candida albicans thr1Delta mutants, but not hom3Delta mutants, were significantly attenuated in virulence. Consistent with the in vivo phenotypes, S. cerevisiae thr1Delta and thr4Delta mutants as well as C. albicans thr1Delta mutants were extremely serum sensitive. In both species, serum sensitivity was suppressed by the addition of threonine, a feedback inhibitor of Hom3p. Because mutation of the HOM3 and HOM6 genes, required for the production of the toxic pathway intermediate homoserine, also suppressed serum sensitivity, we hypothesize that serum sensitivity is a consequence of homoserine accumulation. Serum survival is critical for dissemination, an important virulence determinant: thus, together with the essential nature of C. neoformans threonine synthesis, the cross-species serum sensitivity of thr1Delta mutants makes the fungus specific Thr1p, and likely Thr4p, ideal antifungal drug targets. PMID- 20305005 TI - Increased sclerostin serum levels associated with bone formation and resorption markers in patients with immobilization-induced bone loss. AB - CONTEXT: Sclerostin, a Wnt signaling antagonist on the osteoblasts produced by osteocytes, is regulated by mechanical strain and is implicated in the pathogenesis of disuse bone loss. There are no data on sclerostin in humans. OBJECTIVE: The aim of the study was to evaluate sclerostin in patients immobilized after stroke, compared with control subjects, and to analyze its relationship with markers of bone formation and resorption. DESIGN: This was a cross-sectional study. SETTING AND PATIENTS: We studied 40 postmenopausal women immobilized after a single episode of stroke 6 months or longer after onset, and 40 postmenopausal women from the general community. Bone status was assessed by quantitative ultrasound measurements at the calcaneus. Bone alkaline phosphatase (b-AP), carboxy-terminal telopeptide of type I collagen (CrossLaps), and sclerostin were evaluated by ELISA. We also used ELISA to measure serum levels of Dickkopf-1, another soluble inhibitor of Wnt/beta-catenin signaling, highly expressed by osteocytes. RESULTS: Immobilized patients had higher sclerostin serum levels (median 0.975 ng/ml; 25th to 75th percentiles 0.662-1.490) than controls (median 0.300 ng/ml; 25th to 75th percentiles 0.165-0.400: P < 0.0001) and an increased bone turnover with a more significant rise in bone resorption (CrossLaps) than formation (b-AP) markers. Sclerostin correlated negatively with b-AP (r = -0.911; P < 0.0001) and positively with CrossLaps (r = 0.391; P = 0.012). Dickkopf-1 did not significantly differ between the groups. Patients also had quantitative ultrasound measurements index lower than controls (P < 0.001). CONCLUSIONS: This study shows for the first time that long-term immobilized patients present hypersclerostinemia associated with reduced bone formation, and suggests that sclerostin could be a link between mechanical unloading and disuse osteoporosis in humans. PMID- 20305004 TI - Genetic and molecular characterization of a cryptochrome from the filamentous fungus Neurospora crassa. AB - In plants and animals, cryptochromes function as either photoreceptors or circadian clock components. We have examined the cryptochrome from the filamentous fungus Neurospora crassa and demonstrate that Neurospora cry encodes a DASH-type cryptochrome that appears capable of binding flavin adenine dinucleotide (FAD) and methenyltetrahydrofolate (MTHF). The cry transcript and CRY protein levels are strongly induced by blue light in a wc-1-dependent manner, and cry transcript is circadianly regulated, with a peak abundance opposite in phase to frq. Neither deletion nor overexpression of cry appears to perturb the free-running circadian clock. However, cry disruption knockout mutants show a small phase delay under circadian entrainment. Using electrophoretic mobility shift assays (EMSA), we show that CRY is capable of binding single- and double stranded DNA (ssDNA and dsDNA, respectively) and ssRNA and dsRNA. Whole-genome microarray experiments failed to identify substantive transcriptional regulatory activity of cry under our laboratory conditions. PMID- 20305006 TI - Determinants of severe hypoglycemia complicating type 2 diabetes: the Fremantle diabetes study. AB - CONTEXT: There are limited published data characterizing severe hypoglycemia complicating type 2 diabetes. OBJECTIVE: The objective of the study was to determine the incidence and predictors of severe hypoglycemia in community dwelling type 2 patients. DESIGN: This was a longitudinal observational cohort study. SETTING: This was a community-based study. PATIENTS: There were 616 patients (mean age 67.0 yr, 52.3% males, median diabetes duration 7.7 yr) assessed in 1998 and followed up to the end of June 2006. MAIN OUTCOME MEASURES: Severe hypoglycemia defined as that requiring ambulance attendance, emergency department services, and/or hospitalization. Cox proportional hazards modeling was used to determine predictors of first episode, and Poisson, negative binomial, zero-inflated Poisson, and zero-inflated negative binomial regression models identified predictors of frequency. RESULTS: Fifty-two (8.4%) experienced 66 episodes during 3953 patient-years (incidence 1.7 per 100 patient-years). Those experiencing severe hypoglycemia had one to four episodes. Significant independent predictors of time to first episode were duration of insulin treatment, estimated glomerular filtration rate less than 60 ml/min per 1.73 m(2), peripheral neuropathy, education beyond primary level, and past severe hypoglycemia. The zero-inflated negative binomial provided the best model of severe hypoglycemia frequency. Lower fasting serum glucose and higher glycosylated hemoglobin were significantly associated with frequency, whereas patients at minimal risk of repeated severe hypoglycemia were unlikely to use insulin or to have short-duration insulin treatment, to have renal impairment or peripheral neuropathy, or to be educated beyond primary level. CONCLUSIONS: Duration of insulin treatment was confirmed as an independent risk factor for severe hypoglycemia. The novel association with educational attainment suggests knowledge-driven intensive glycemic self-management. The positive relationship between frequency and glycosylated hemoglobin may identify patients with unstable glycemic control. PMID- 20305007 TI - Hormonal profile heterogeneity and short-term physical risk in restrictive anorexia nervosa. AB - CONTEXT: The relevance of hormonal assessment in anorexia nervosa (AN) management is still unclear. The short-term physical risk during undernutrition period of the disease is partially predicted by anthropometric and electrolytic parameters. OBJECTIVE: The objective of the study was to evaluate hormonal profiles in a large cohort of AN and their relationship with critical states. DESIGN AND SETTING: This was an observational monocentric cross-sectional study performed in the endocrinological unit. PATIENTS AND OTHER PARTICIPANTS: Participants included 210 young female subjects with restrictive-type AN and 42 female controls of comparable age. MAIN OUTCOME MEASURES: The following hormonal parameters were measured: thyroid hormones, GH, IGF-I, cortisol, oestradiol, FSH, LH, SHBG, dehydroepiandrosterone sulfate, plasma metanephrines, and bone markers. Their relation with registered short-term evolution of AN subjects after hormonal assessment was evaluated. RESULTS: Except for metanephrines and dehydroepiandrosterone sulfate, most of the hormonal abnormalities previously reported in AN were confirmed. The manifestation of these hormonal abnormalities started below different body mass index (BMI) levels, ranging between 17 and 15 kg/m(2), even though an important percentage of normal values for every parameter was still noticed for very low BMIs. All patients who developed critical states during the 3 months after the hormonal assessment presented with BMI less than 15 kg/m(2) and a very increased level of cortisol, GH, and increased values of metanephrines. CONCLUSIONS: The hormonal response to undernutrition is heterogeneous in a large population with restrictive AN. In clinical practice, metanephrines, GH, and/or cortisol data could be used as important predictors for severe short-term outcome. PMID- 20305008 TI - Minireview: update on incretin biology: focus on glucagon-like peptide-1. AB - The incretin hormone, glucagon-like peptide-1 (GLP-1), is now being used in the clinic to enhance insulin secretion and reduce body weight in patients with type 2 diabetes. Although much is already known about the biology of GLP-1, much remains to be understood. Hence, this review will consider recent findings related to the potential for enhancing endogenous levels of GLP-1 through selective use of secretagogues and the beneficial cardiovascular, neuroprotective, and immunomodulatory effects of GLP-1, as well as the possible effects of GLP-1 to enhance beta-cell growth and/or to induce pancreatitis or thyroid cancer. Finally, the potential for molecular medicine to enhance the success of GLP-1 therapy in the clinic is considered. A better understanding of the fundamental biology of GLP-1 may lead to new therapeutic modalities for the clinical use of this intestinal hormone. PMID- 20305009 TI - Isolation and identification of ATP-secreting bacteria from mice and humans. AB - In a recent report, ATP, which was possibly secreted by some intestinal bacteria, was shown to cause colitis in mice via Th17 cell differentiation. However, the ATP-secreting bacteria have not been isolated and identified. In the present study, we report that Enterococcus gallinarum, which is a vancomycin-resistant Gram-positive coccus isolated from mice and humans, secretes ATP. PMID- 20305010 TI - Prevalence of rotavirus, adenovirus, norovirus, and astrovirus infections and coinfections among hospitalized children in northern France. AB - From January to December 2007, 973 stool specimens were prospectively collected from children hospitalized for gastroenteritis signs or from neonates and premature cases who were born in two French hospital settings in the north of France. They were tested by rapid enzyme immunoassay (EIA) analyses for rotavirus and adenovirus and by two commercially available ELISA tests for the detection of norovirus and astrovirus. The overall rates of prevalence for rotavirus, norovirus, adenovirus, and astrovirus were 21, 13, 5, and 1.8%, respectively, and they did not significantly differ between the two hospital settings (P=0.12). Mixed virus infections were detected in 32 (3.3%) of the 973 study children and were associated with norovirus in 21 (66%) infants, including 5 premature cases. From fall to spring, norovirus infections accounted for 52% of documented gastroenteritidis viral infections at a time when rotavirus was epidemic, resulting in mixed norovirus and rotavirus gastrointestinal tract infections. Of the 367 documented viral gastroenteritis cases, 15 (4.1%) were identified as nosocomial infections, 5 of which occurred in premature cases. These findings highlight the need to implement norovirus and astrovirus ELISA detection assays in association with rapid EIA rotavirus and adenovirus detection assays for the clinical diagnosis and the nosocomial prevention of gastroenteritis viral infections in pediatric departments. PMID- 20305011 TI - First report of treatment of Anaerobiospirillum succiniciproducens bloodstream infection with levofloxacin. AB - The full extent of the clinical spectrum and optimal therapy of Anaerobiospirillum succiniciproducens infections remains to be determined. We describe the first case of bloodstream infection (BSI) due to A. succiniciproducens in an asymptomatic elderly male with poor dentition that was treated with levofloxacin. PMID- 20305012 TI - Noroviruses as a cause of diarrhea in travelers to Guatemala, India, and Mexico. AB - Noroviruses (NoVs) are increasingly being recognized as an important enteric pathogen of gastroenteritis worldwide. The prevalence of NoVs as a cause of diarrhea acquired by travelers in developing countries is not well known. We examined the prevalence and importance of NoV infection in three international traveler cohorts with diarrhea acquired in three developing regions of the world, Mexico, Guatemala, and India. We also characterized the demographics and symptoms associated with NoV diarrhea in these travelers. Stool samples from 571 international travelers with diarrhea were evaluated for traditional enteropathogens. NoVs were identified using reverse transcription-PCR and probe hybridization. NoVs were identified in 10.2% of cases of travelers' diarrhea and, overall, was the second most common pathogen, following diarrheagenic Escherichia coli. The detection of NoV diarrhea significantly varied over the three study time periods in Guadalajara, Mexico, ranging from 3 of 98 (3.0%) diarrheal stools to 12 of 100 (12.0%) fecal specimens (P=0.03). The frequency of NoV diarrhea was also dependent upon the geographic region, with 17 of 100 (17.0%) travelers to Guatemala, 23 of 194 (11.9%) travelers to India, and 3 of 79 (3.8%) travelers to Mexico testing positive for NoVs from 2002 to 2003 (P=0.02). NoVs are important pathogens of travelers' diarrhea in multiple regions of the world. Significant variation in the prevalence of NoV diarrhea and in the predominant genogroup infecting travelers was demonstrated, dependent upon the specific geographic location and over time. PMID- 20305013 TI - Detection and identification of Staphylococcus lugdunensis are not hampered by use of defibrinated horse blood in blood agar plates. PMID- 20305014 TI - Toxin profiling of Staphylococcus aureus strains involved in varicella superinfection. AB - The most common complications of varicella are bacterial skin and soft tissue infections, generally due to Staphylococcus aureus and group A beta-hemolytic streptococci. The aim of this study was to characterize the toxin and antibiotic resistance profiles of S. aureus isolates involved in varicella complications. Between 2002 and 2007, the French Reference Centre for Staphylococci collected 58 S. aureus isolates involved in varicella superinfection. All the isolates were characterized by screening for 12 toxin genes, agr typing, and mecA gene detection; some isolates were also studied by spa typing, multilocus sequence typing (MLST), and resistance profiling. A major toxin gene was detected in 53% (31/58) of the isolates (genes for exfoliative toxins A and B, 17.2%; Panton Valentine leukocidin gene, 8.6%; toxic shock syndrome toxin 1 gene, 27.6%). Most clinical manifestations were directly compatible with the classical activity of these toxins. Nineteen isolates (33%) were resistant to methicillin, and 12 of these isolates belonged to an emerging agr-2, ST5 clone that harbors the toxic shock syndrome toxin 1 gene. These data should be considered in the management and treatment of patients with varicella complicated by S. aureus superinfection. Antibiotics that decrease toxin production, such as clindamycin, may provide benefit, and their efficacy against bacterial superinfections in children with varicella should be studied. PMID- 20305015 TI - Quantitative PCR assessments of bacterial species in women with and without bacterial vaginosis. AB - Knowledge of the abundance of bacterial species in vaginal communities will help us to better understand their role in health and disease. However, progress in this field has been limited because quantifying bacteria in natural specimens is an arduous process. We developed quantitative real-time PCR (qPCR) assays to facilitate assessments of bacterial abundance in vaginal specimens and evaluated the utility of these assays by measuring species abundance in patients whose vaginal floras were clinically described as normal, intermediate, or bacterial vaginosis (BV) as defined by Nugent's criteria. The qPCR measurements showed that Lactobacillus species were predominant in normal vaginal specimens and that high Lactobacillus crispatus and Lactobacillus jensenii abundance was specific to normal specimens, while Lactobacillus iners abundance was high in all categories including BV. The abundances of all non-Lactobacillus species were higher in BV specimens than in normal specimens. Prevotella species were prevalent in all specimens and represented a high percentage of total species in BV specimens. qPCR assays can be a useful tool for describing the structure of vaginal communities and elucidating their role in health and disease. PMID- 20305016 TI - Genome assembly quality: assessment and improvement using the neutral indel model. AB - We describe a statistical and comparative-genomic approach for quantifying error rates of genome sequence assemblies. The method exploits not substitutions but the pattern of insertions and deletions (indels) in genome-scale alignments for closely related species. Using two- or three-way alignments, the approach estimates the amount of aligned sequence containing clusters of nucleotides that were wrongly inserted or deleted during sequencing or assembly. Thus, the method is well-suited to assessing fine-scale sequence quality within single assemblies, between different assemblies of a single set of reads, and between genome assemblies for different species. When applying this approach to four primate genome assemblies, we found that average gap error rates per base varied considerably, by up to sixfold. As expected, bacterial artificial chromosome (BAC) sequences contained lower, but still substantial, predicted numbers of errors, arguing for caution in regarding BACs as the epitome of genome fidelity. We then mapped short reads, at approximately 10-fold statistical coverage, from a Bornean orangutan onto the Sumatran orangutan genome assembly originally constructed from capillary reads. This resulted in a reduced gap error rate and a separation of error-prone from high-fidelity sequence. Over 5000 predicted indel errors in protein-coding sequence were corrected in a hybrid assembly. Our approach contributes a new fine-scale quality metric for assemblies that should facilitate development of improved genome sequencing and assembly strategies. PMID- 20305017 TI - Deep RNA sequencing at single base-pair resolution reveals high complexity of the rice transcriptome. AB - Understanding the dynamics of eukaryotic transcriptome is essential for studying the complexity of transcriptional regulation and its impact on phenotype. However, comprehensive studies of transcriptomes at single base resolution are rare, even for modern organisms, and lacking for rice. Here, we present the first transcriptome atlas for eight organs of cultivated rice. Using high-throughput paired-end RNA-seq, we unambiguously detected transcripts expressing at an extremely low level, as well as a substantial number of novel transcripts, exons, and untranslated regions. An analysis of alternative splicing in the rice transcriptome revealed that alternative cis-splicing occurred in approximately 33% of all rice genes. This is far more than previously reported. In addition, we also identified 234 putative chimeric transcripts that seem to be produced by trans-splicing, indicating that transcript fusion events are more common than expected. In-depth analysis revealed a multitude of fusion transcripts that might be by-products of alternative splicing. Validation and chimeric transcript structural analysis provided evidence that some of these transcripts are likely to be functional in the cell. Taken together, our data provide extensive evidence that transcriptional regulation in rice is vastly more complex than previously believed. PMID- 20305018 TI - Succession of the bacterial community and dynamics of hydrogen producers in a hydrogen-producing bioreactor. AB - Variation in the hydrogen production rate was consistent with the succession of dominant bacteria during the batch fermentation process. Denaturing gradient gel electrophoresis (DGGE) of 16S rRNA genes and quantitative analysis of the hydA genes at both the DNA and mRNA levels confirmed that Clostridium perfringens was the most dominant hydrogen producer in the bioreactor. PMID- 20305019 TI - Characterization of triclosan-resistant mutants reveals multiple antimicrobial resistance mechanisms in Rhodospirillum rubrum S1H. AB - Antimicrobial resistance mechanisms were identified in 11 spontaneous high- and low-level triclosan resistance (Tcs(r)) mutants of Rhodospirillum rubrum S1H by genotyping complemented with transcriptional analyses, antibiotic resistance screening, and membrane permeability analyses. High-end Tcs(r) (MIC = 8 mg/liter) was the result of a FabI1(G98V) mutation. This point mutation led to an even higher level of Tcs(r) (MIC > or = 16 mg/liter) in combination with constitutive upregulation of mexB and mexF efflux pump homologs. Hence, a mechanistic synergy of constitutive efflux pump expression and a FabI1 point mutation could prevent TCS-induced cell permeabilization, which was shown to occur between 4 and 8 mg/liter TCS in the R. rubrum S1H parent strain. Low-level Tcs(r) mutants constitutively upregulated the emrAB, mexAB, and/or mexF homolog. The mutants that overexpressed emrAB also derepressed the micropollutant-upregulated factors mufA1 and mufM. In some cases, low-level Tcs(r) decreased innate resistance to ampicillin and tetracycline, while in others, a triclosan-induced antibiotic cross-resistance was shown for chloramphenicol and carbenicillin. This study showed that the TCS resistance degree is dependent of the initial exposure concentration in Rhodospirillum rubrum S1H and that similar resistance degrees can be the result of different defense mechanisms, which all have distinct antibiotic cross-resistance profiles. PMID- 20305020 TI - Lepidopteran-active variable-region sequence imparts coleopteran activity in eCry3.1Ab, an engineered Bacillus thuringiensis hybrid insecticidal protein. AB - A unique, coleopteran-active protein, termed eCry3.1Ab, was generated following variable-region exchange of a Bacillus thuringiensis lepidopteran-active protein, Cry1Ab, with a Cry3A region. Our results support the hypothesis that this variable-region exchange is responsible for imparting strong bioactivity against the larvae of western corn rootworm (WCR) (Diabrotica virgifera virgifera LeConte), a pest species which is not susceptible to either parent protein sequence. This study demonstrates the potential of successfully engineering a portion(s) of a lepidopteran-active B. thuringiensis sequence so that it has activity against coleopterans. Further elucidation of the eCry3.1Ab activity indicated the importance of variable regions 4 to 6 that were derived from Cry1Ab instead of Cry1Ac. There was some flexibility in making domain III of engineered hybrid insecticidal proteins even more Cry1Ab-like and retaining activity, while there was less flexibility in making domain III more Cry3A-like and retaining activity. In vitro binding studies with brush border membrane vesicles demonstrated that there was specific binding of chymotrypsin-processed modified Cry3A (mCry3A), which was not diminished by addition of a 100-fold molar excess of chymotrypsin-processed eCry3.1Ab or unprocessed eCry3.1Ab. In addition, in the converse experiment, specific binding of chymotrypsin-processed eCry3.1Ab was not diminished by the presence of a 75-fold molar excess of chymotrypsin-processed mCry3A. These data support the hypothesis that eCry3.1Ab can interact with different binding sites than the activated form of mCry3A in the WCR brush border and may provide a different mode of action from the standpoint of resistance management. PMID- 20305021 TI - Isolation and characterization of a mutant of the marine bacterium Alcanivorax borkumensis SK2 defective in lipid biosynthesis. AB - In many microorganisms, the key enzyme responsible for catalyzing the last step in triacylglycerol (TAG) and wax ester (WE) biosynthesis is an unspecific acyltransferase which is also referred to as wax ester synthase/acyl coenzyme A (acyl-CoA):diacylglycerol acyltransferase (WS/DGAT; AtfA). The importance and function of two AtfA homologues (AtfA1 and AtfA2) in the biosynthesis of TAGs and WEs in the hydrocarbon-degrading marine bacterium Alcanivorax borkumensis SK2 have been described recently. However, after the disruption of both the AtfA1 and AtfA2 genes, reduced but substantial accumulation of TAGs was still observed, indicating the existence of an alternative TAG biosynthesis pathway. In this study, transposon-induced mutagenesis was applied to an atfA1 atfA2 double mutant to screen for A. borkumensis mutants totally defective in biosynthesis of neutral lipids in order to identify additional enzymes involved in the biosynthesis of these lipids. At the same time, we have searched for a totally TAG-negative mutant in order to study the function of TAGs in A. borkumensis. Thirteen fluorescence-negative mutants were identified on Nile red ONR7a agar plates and analyzed for their abilities to synthesize lipids. Among these, mutant 2 M(131) was no longer able to synthesize and accumulate TAGs if pyruvate was used as the sole carbon source. The transposon insertion was localized in a gene encoding a putative cytochrome c family protein (ABO_1185). Growth and TAG accumulation experiments showed that the disruption of this gene resulted in the absence of TAGs in 2 M(131) but that growth was not affected. In cells of A. borkumensis SK2 grown on pyruvate as the sole carbon source, TAGs represented about 11% of the dry weight of the cells, while in the mutant 2 M(131), TAGs were not detected by thin-layer and gas chromatography analyses. Starvation and lipid mobilization experiments revealed that the lipids play an important role in the survival of the cells. The function of neutral lipids in A. borkumensis SK2 is discussed. PMID- 20305023 TI - Sequences essential for transmission of Spiroplasma citri by its leafhopper vector, Circulifer haematoceps, revealed by plasmid curing and replacement based on incompatibility. AB - Spiroplasma citri GII3 contains highly related low-copy-number plasmids pSci1 to 6. Despite the strong similarities between their replication regions, these plasmids coexist in the spiroplasma cells, indicating that they are mutually compatible. The pSci1 to -6 plasmids encode the membrane proteins known as S. citri adhesion-related proteins (ScARPs) (pSci1 to -5) and the hydrophilic protein P32 (pSci6), which had been tentatively associated with insect transmission, as they were not detected in non-insect-transmissible strains. With the aim of further investigating the role of plasmid-encoded determinants in insect transmission, we have constructed S. citri mutant strains that differ in their plasmid contents by developing a plasmid curing/replacement strategy based on the incompatibility of plasmids having identical replication regions. Experimental transmission of these S. citri plasmid mutants through injection into the leafhopper vector Circulifer haematoceps revealed that pSci6, more precisely, the pSci6_06 coding sequence, encoding a protein of unknown function, was essential for transmission. In contrast, ScARPs and P32 were dispensable for both acquisition and transmission of the spiroplasmas by the leafhopper vector, even though S. citri mutants lacking pSci1 to -5 (encoding ScARPs) were acquired and transmitted at lower efficiencies than the wild-type strain GII3. PMID- 20305024 TI - Denitrifying bacteria isolated from terrestrial subsurface sediments exposed to mixed-waste contamination. AB - In terrestrial subsurface environments where nitrate is a critical groundwater contaminant, few cultivated representatives are available to verify the metabolism of organisms that catalyze denitrification. In this study, five species of denitrifying bacteria from three phyla were isolated from subsurface sediments exposed to metal radionuclide and nitrate contamination as part of the U.S. Department of Energy's Oak Ridge Integrated Field Research Challenge (OR IFRC). Isolates belonged to the genera Afipia and Hyphomicrobium (Alphaproteobacteria), Rhodanobacter (Gammaproteobacteria), Intrasporangium (Actinobacteria), and Bacillus (Firmicutes). Isolates from the phylum Proteobacteria were complete denitrifiers, whereas the Gram-positive isolates reduced nitrate to nitrous oxide. rRNA gene analyses coupled with physiological and genomic analyses suggest that bacteria from the genus Rhodanobacter are a diverse population of denitrifiers that are circumneutral to moderately acidophilic, with a high relative abundance in areas of the acidic source zone at the OR-IFRC site. Based on genome analysis, Rhodanobacter species contain two nitrite reductase genes and have not been detected in functional-gene surveys of denitrifying bacteria at the OR-IFRC site. Nitrite and nitrous oxide reductase gene sequences were recovered from the isolates and from the terrestrial subsurface by designing primer sets mined from genomic and metagenomic data and from draft genomes of two of the isolates. We demonstrate that a combination of cultivation and genomic and metagenomic data is essential to the in situ characterization of denitrifiers and that current PCR-based approaches are not suitable for deep coverage of denitrifiers. Our results indicate that the diversity of denitrifiers is significantly underestimated in the terrestrial subsurface. PMID- 20305025 TI - Systematic evaluation of the efficacy of chlorine dioxide in decontamination of building interior surfaces contaminated with anthrax spores. AB - Efficacy of chlorine dioxide (CD) gas generated by two distinct generation systems, Sabre (wet system with gas generated in water) and ClorDiSys (dry system with gas generated in air), was evaluated for inactivation of Bacillus anthracis spores on six building interior surfaces. The six building materials included carpet, acoustic ceiling tile, unpainted cinder block, painted I-beam steel, painted wallboard, and unpainted pinewood. There was no statistically significant difference in the data due to the CD generation technology at a 95% confidence level. Note that a common method of CD gas measurement was used for both wet and dry CD generation types. Doses generated by combinations of different concentrations of CD gas (500, 1,000, 1,500, or 3,000 parts per million of volume [ppmv]) and exposure times (ranging between 0.5 and 12 h) were used to evaluate the relative role of fumigant exposure period and total dose in the decontamination of building surfaces. The results showed that the time required to achieve at least a 6-log reduction in viable spores is clearly a function of the material type on which the spores are inoculated. The wood and cinder block coupons required a longer exposure time to achieve a 6-log reduction. The only material showing a clear statistical difference in rate of decay of viable spores as a function of concentration was cinder block. For all other materials, the profile of spore kill (i.e., change in number of viable spores with exposure time) was not dependent upon fumigant concentration (500 to 3,000 ppmv). The CD dose required for complete spore kill on biological indicators (typically, 1E6 spores of Bacillus atrophaeus on stainless steel) was significantly less than that required for decontamination of most of the building materials tested. PMID- 20305026 TI - Mechanistic aspects of adenovirus serotype 2 inactivation with free chlorine. AB - Free chlorine is an effective disinfectant for controlling adenoviruses in drinking water, but little is known about the underlying inactivation mechanisms. The objective of this study was to elucidate the molecular components of adenovirus type 2 (Ad2) targeted by free chlorine during the inactivation process. The effects of free chlorine treatment on several Ad2 molecular components and associated life cycle events were compared to its effect on the ability of adenovirus to complete its life cycle, i.e., viability. Free chlorine treatment of Ad2 virions did not impair their ability to interact with monoclonal antibodies specific for hexon and fiber proteins of the Ad2 capsid, as measured by enzyme-linked immunosorbent assays, nor did it impair their interaction with recombinant, purified Coxsackie-adenovirus receptor (CAR) proteins in vitro. Free chlorine-treated Ad2 virions also retained their ability to bind to CAR receptors on A549 cell monolayers, despite being unable to form plaques, suggesting that free chlorine inactivates Ad2 by inhibiting a postbinding event of the Ad2 life cycle. DNA isolated from Ad2 virions that had been inactivated by free chlorine was able to be amplified by PCR, indicating that genome damage was not the cause of inactivation. However, inactivated Ad2 virions were unable to express E1A viral proteins during infection of A549 host cells, as measured by using immunoblotting. Collectively, these results indicate that free chlorine inactivates adenovirus by damaging proteins that govern life cycle processes occurring after host cell attachment, such as endocytosis, endosomal lysis, or nuclear delivery. PMID- 20305022 TI - Application of molecular techniques to elucidate the influence of cellulosic waste on the bacterial community structure at a simulated low-level-radioactive waste site. AB - Low-level-radioactive-waste (low-level-waste) sites, including those at various U.S. Department of Energy sites, frequently contain cellulosic waste in the form of paper towels, cardboard boxes, or wood contaminated with heavy metals and radionuclides such as chromium and uranium. To understand how the soil microbial community is influenced by the presence of cellulosic waste products, multiple soil samples were obtained from a nonradioactive model low-level-waste test pit at the Idaho National Laboratory. Samples were analyzed using 16S rRNA gene clone libraries and 16S rRNA gene microarray (PhyloChip) analyses. Both methods revealed changes in the bacterial community structure with depth. In all samples, the PhyloChip detected significantly more operational taxonomic units, and therefore relative diversity, than the clone libraries. Diversity indices suggest that diversity is lowest in the fill and fill-waste interface (FW) layers and greater in the wood waste and waste-clay interface layers. Principal-coordinate analysis and lineage-specific analysis determined that the Bacteroidetes and Actinobacteria phyla account for most of the significant differences observed between the layers. The decreased diversity in the FW layer and increased members of families containing known cellulose-degrading microorganisms suggest that the FW layer is an enrichment environment for these organisms. These results suggest that the presence of the cellulosic material significantly influences the bacterial community structure in a stratified soil system. PMID- 20305027 TI - Abundance and expression of enantioselective rdpA and sdpA dioxygenase genes during degradation of the racemic herbicide (R,S)-2-(2,4 dichlorophenoxy)propionate in soil. AB - The rdpA and sdpA genes encode two enantioselective alpha-ketoglutarate-dependent dioxygenases catalyzing the initial step of microbial degradation of the chiral herbicide (R,S)-2-(2,4-dichlorophenoxy)propionate (R,S-dichlorprop). Primers were designed to assess abundance and transcription dynamics of rdpA and sdpA genes in a natural agricultural soil. No indigenous rdpA genes were detected, but sdpA genes were present at levels of approximately 10(3) copies g of soil(-1). Cloning and sequencing of partial sdpA genes revealed a high diversity within the natural sdpA gene pool that could be divided into four clusters by phylogenetic analysis. BLASTp analysis of deduced amino acids revealed that members of cluster I shared 68 to 69% identity, cluster II shared 78 to 85% identity, cluster III shared 58 to 64% identity, and cluster IV shared 55% identity to their closest SdpA relative in GenBank. Expression of rdpA and sdpA in Delftia acidovorans MC1 inoculated in soil was monitored by reverse transcription quantitative real-time PCR (qPCR) during in situ degradation of 2 and 50 mg kg(-1) of (R,S)-dichlorprop. (R,S)-Dichlorprop amendment created a clear upregulation of both rdpA and sdpA gene expression during the active phase of (14)C-labeled (R,S)-dichlorprop mineralization, particularly following the second dose of 50 mg kg(-1) herbicide. Expression of both genes was maintained at a low constitutive level in nonamended soil microcosms. This study is the first to report the presence of indigenous sdpA genes recovered directly from natural soil and also comprises the first investigation into the transcription dynamics of two enantioselective dioxygenase genes during the in situ degradation of the herbicide (R,S)-dichlorprop in soil. PMID- 20305028 TI - Anaerobic oxidation of fatty acids and alkenes by the hyperthermophilic sulfate reducing archaeon Archaeoglobus fulgidus. AB - Archaeoglobus fulgidus oxidizes fatty acids (C(4) to C(18)) and n-alk-1-enes (C(12:1) to C(21:1)) in the presence of thiosulfate as a terminal electron acceptor. End products of metabolism were CO(2) and sulfide. Growth on perdeuterated hexadecene yielded C(15)- to C(17)-labeled fatty acids as metabolites, thus confirming the ability of A. fulgidus to oxidize alkyl chains. PMID- 20305029 TI - Heterologous expression of mutated eburicol 14alpha-demethylase (CYP51) proteins of Mycosphaerella graminicola to assess effects on azole fungicide sensitivity and intrinsic protein function. AB - The recent decrease in the sensitivity of the Western European population of the wheat pathogen Mycosphaerella graminicola to azole fungicides has been associated with the emergence and subsequent spread of mutations in the CYP51 gene, encoding the azole target sterol 14alpha-demethylase. In this study, we have expressed wild-type and mutated M. graminicola CYP51 (MgCYP51) variants in a Saccharomyces cerevisiae mutant carrying a doxycycline-regulatable tetO(7)-CYC promoter controlling native CYP51 expression. We have shown that the wild-type MgCYP51 protein complements the function of the orthologous protein in S. cerevisiae. Mutant MgCYP51 proteins containing amino acid alterations L50S, Y459D, and Y461H and the two-amino-acid deletion DeltaY459/G460, commonly identified in modern M. graminicola populations, have no effect on the capacity of the M. graminicola protein to function in S. cerevisiae. We have also shown that the azole fungicide sensitivities of transformants expressing MgCYP51 variants with these alterations are substantially reduced. Furthermore, we have demonstrated that the I381V substitution, correlated with the recent decline in the effectiveness of azoles, destroys the capacity of MgCYP51 to complement the S. cerevisiae mutant when introduced alone. However, when I381V is combined with changes between residues Y459 and Y461, the function of the M. graminicola protein is partially restored. These findings demonstrate, for the first time for a plant pathogenic fungus, the impacts that naturally occurring CYP51 alterations have on both azole sensitivity and intrinsic protein function. In addition, we also provide functional evidence underlying the order in which CYP51 alterations in the Western European M. graminicola population emerged. PMID- 20305030 TI - Constitutive expression of the proteorhodopsin gene by a flavobacterium strain representative of the proteorhodopsin-producing microbial community in the North Sea. AB - Proteorhodopsin (PR), a photoactive proton pump containing retinal, is present in approximately half of all bacteria in the ocean, but its physiological role is still unclear, since very few strains carrying the PR gene have been cultured. The aim of this work was to characterize PR diversity in a North Sea water sample, cultivate a strain representative of North Sea PR clusters, and study the effects of light and carbon concentration on the expression of the PR gene. A total of 117 PR sequences, of which 101 were unique, were obtained from a clone library of PCR-amplified PR gene fragments. Of the North Sea PRs, 97% were green light absorbing, as inferred from the amino acid at position 105; 67% of the PR protein fragments showed closest similarity to PRs from Alphaproteobacteria, 4% showed closest similarity to PRs from Gammaproteobacteria, and 29% showed closest similarity to PRs from "Bacteroidetes"/Flavobacteria. The dominant PR cluster (comprising 18% of all PRs) showed a high degree of similarity to the PR from the cultivated Roseobacter strain HTCC2255. The relative abundances of the North Sea PR clusters were confirmed by quantitative PCR. They were detected in metagenomic fragments from coastal oceans worldwide with various degrees of abundance. Several hundred bacterial strains from the North Sea water sample were cultivated on oligocarbophilic media. By screening with degenerate primers, two strains carrying the PR gene were identified. Their 16S rRNA gene sequences were identical and affiliated with a Bacteroidetes subcluster from the North Sea. The PR sequence of isolate PRO95 was completed by chromosomal walking. It was 76% identical to that of Dokdonia donghaensis MED134 and was functional, as indicated by the signature amino acids. PRO95 expressed its PR gene in liquid media containing between 9.7 and 121 mM carbon, both in the light and in the dark. Growth was not enhanced by light. Thus, the detection of the physiological role of PR may require more sensitive methods. PMID- 20305031 TI - High-level congruence of Myrionecta rubra prey and Dinophysis species plastid identities as revealed by genetic analyses of isolates from Japanese coastal waters. AB - We analyzed cryptophyte nucleomorph 18S rRNA gene sequences retained in natural Myrionecta rubra cells and plastid 16S rRNA gene and psbA sequences retained in natural cells of several Dinophysis species collected from Japanese coastal waters. A total of 715 nucleomorph sequences obtained from 134 M. rubra cells and 564 plastid 16S rRNA gene and 355 psbA sequences from 71 Dinophysis cells were determined. Almost all sequences in M. rubra and Dinophysis spp. were identical to those of Teleaulax amphioxeia, suggesting that M. rubra in Japanese coastal waters preferentially ingest T. amphioxeia. The remaining sequences were closely related to those of Geminigera cryophila and Teleaulax acuta. Interestingly, 37 plastid 16S rRNA gene sequences, which were different from T. amphioxeia and amplified from Dinophysis acuminata and Dinophysis norvegica cells, were identical to the sequence of a D. acuminata cell found in the Greenland Sea, suggesting that a widely distributed and unknown cryptophyte species is also preyed upon by M. rubra and subsequently sequestered by Dinophysis. To confirm the reliability of molecular identification of the cryptophyte Teleaulax species detected from M. rubra and Dinophysis cells, the nucleomorph and plastid genes of Teleaulax species isolated from seawaters were also analyzed. Of 19 isolates, 16 and 3 clonal strains were identified as T. amphioxeia and T. acuta, respectively, and no sequence variation was confirmed within species. T. amphioxeia is probably the primary source of prey for M. rubra in Japanese coastal waters. An unknown cryptophyte may serve as an additional source, depending on localities and seasons. PMID- 20305032 TI - DNA probes for unambiguous identification of Listeria monocytogenes epidemic clone II strains. AB - Listeria monocytogenes epidemic clone II (ECII) strains have been responsible for two major multistate outbreaks of food-borne listeriosis in the United States, but their prevalence and ecology remain poorly understood. In this study, we describe DNA probes that unambiguously identify this clonal group. These probes were able to differentiate ECII strains of outbreak, sporadic, or environmental origin from other L. monocytogenes strains of the same serotype (4b). PMID- 20305033 TI - Role of antioxidant enzymes in bacterial resistance to organic acids. AB - Growth in aerobic environments has been shown to generate reactive oxygen species (ROS) and to cause oxidative stress in most organisms. Antioxidant enzymes (i.e., superoxide dismutases and hydroperoxidases) and DNA repair mechanisms provide protection against ROS. Acid stress has been shown to be associated with the induction of Mn superoxide dismutase (MnSOD) in Lactococcus lactis and Staphylococcus aureus. However, the relationship between acid stress and oxidative stress is not well understood. In the present study, we showed that mutations in the gene coding for MnSOD (sodA) increased the toxicity of lactic acid at pH 3.5 in Streptococcus thermophilus. The inclusion of the iron chelators 2,2'-dipyridyl (DIP), diethienetriamine-pentaacetic acid (DTPA), and O phenanthroline (O-Phe) provided partial protection against 330 mM lactic acid at pH 3.5. The results suggested that acid stress triggers an iron-mediated oxidative stress that can be ameliorated by MnSOD and iron chelators. These findings were further validated in Escherichia coli strains lacking both MnSOD and iron SOD (FeSOD) but expressing a heterologous MnSOD from S. thermophilus. We also found that, in E. coli, FeSOD did not provide the same protection afforded by MnSOD and that hydroperoxidases are equally important in protecting the cells against acid stress. These findings may explain the ability of some microorganisms to survive better in acidified environments, as in acid foods, during fermentation and accumulation of lactic acid or during passage through the low pH of the stomach. PMID- 20305034 TI - No protection of the ovarian follicle pool with the use of GnRH-analogues or oral contraceptives in young women treated with escalated BEACOPP for advanced-stage Hodgkin lymphoma. Final results of a phase II trial from the German Hodgkin Study Group. AB - BACKGROUND: The reduction of treatment-related toxic effects is the main goal in the current trials of the German Hodgkin Study Group (GHSG). In this regard, the protection of the ovarian reserve in young women is very important. Therefore, the GHSG investigated the use of gonadotropin-releasing hormone-analogues (GnRH a) and oral contraceptives (OC) in young women with advanced-stage Hodgkin lymphoma (HL). PATIENTS AND METHODS: Women (18-40 years) were randomly assigned either to receive daily OC or monthly GnRH-a during escalated combination therapy with bleomycin, etoposide, adriamycin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPPesc). Hormonal levels were determined at baseline, during therapy, and at follow-up. RESULTS: The study was closed prematurely after an interim analysis of 12 patients in arm A (OC) and 11 in arm B (GnRH-a), 9 and 10 are assessable for the primary end point. Women's median age was 25 years in both arms. The anti-Mullerian hormone level after at least 12 months was reduced in all patients. For the entire study cohort, the respective ovarian follicle preservation rate was 0% (95% confidence interval 0% to 12%). CONCLUSION: We observed no protection of the ovarian reserve with hormonal co treatment during BEACOPPesc. This result supports efforts of ongoing trials to reduce chemotherapy intensity and toxicity. Alternative strategies for the protection of fertility must be offered to young female HL patients before the start of BEACOPPesc therapy. PMID- 20305035 TI - Impact of adjuvant treatment modalities on the management of patients with stages I-II endometrial stromal sarcoma. AB - PURPOSE: To explore whether adjuvant treatment options may impact on the prognosis in localized endometrial stromal sarcomas (ESSs; stages I and II). The historical options usually discussed in addition to hysterectomy and bilateral salpingoophorectomy (BSO) are active surveillance, pelvic radiotherapy, chemotherapy and hormonal therapy, alone or in combination. PATIENTS AND METHODS: Among 84 consecutive patients treated for ESS at a single referral center, 54 with localized stage disease were identified. Recurrence-free survival and overall survival were estimated and patterns of recurrences described. Univariate and multivariate analyses were carried out. RESULTS: With a median follow-up of 58 months, only one patient had died. None of the 23 patients who had received adjuvant therapy relapsed compared with 13 of 31 patients who had not received any adjuvant therapy. Adjuvant treatments were hormonal therapy (n = 10) and brachytherapy with/without pelvic radiotherapy (n = 13). Almost the majority of relapses were local (92%) and extra-pelvic metastasis was observed in nearly half of the patients (46%). In the multivariate analysis, the major determinants of relapse-free survival were adjuvant treatment, myometrial invasion (P = 0.005) and no BSO (P = 0.005). CONCLUSIONS: In this series, adjuvant treatment of localized ESSs was associated with the absence of recurrence. PMID- 20305036 TI - Clinical features of interstitial lung disease induced by standard chemotherapy (FOLFOX or FOLFIRI) for colorectal cancer. AB - BACKGROUND: Chemotherapy-induced interstitial lung disease (ILD) in colorectal cancer (CRC) patients is rarely reported, but its clinical features remain to be clarified. PATIENTS AND METHODS: Using a computerized database, we retrospectively identified patients who developed ILD from 734 patients with CRC treated with infusional 5-fluorouracil, leucovorin and oxaliplatin (FOLFOX) or infusional 5-fluorouracil, leucovorin and irinotecan (FOLFIRI) from April 2005 to December 2008 at the National Cancer Center Hospital East. RESULTS: Of 734 patients, 11 patients developed ILD (1.5%) and 4 of those patients died (0.54%). Of the 11 patients, 10 showed pulmonary shadows other than lung metastases before chemotherapy. ILD developed during FOLFOX in six patients, at 137 days after completion of FOLFOX in one patient, during oxaliplatin interruption of FOLFOX in one patient and during FOLFIRI in the remaining three patients. FOLFOX had been administered at some point for all ILD patients, with a median of 10 cycles (range 2-17 cycles) and a median dose of administered oxaliplatin of 850 mg/m(2) (range 170-1445 mg/m(2)). CONCLUSIONS: ILD following FOLFOX or FOLFIRI is an uncommon but life-threatening complication. Care must be taken regarding the onset of ILD, not only during but also after chemotherapy for CRC. PMID- 20305038 TI - Structure and serology of O-antigens as the basis for classification of Proteus strains. AB - This review is devoted to structural and serological characteristics of the O antigens (O-polysaccharides) of the lipopolysaccharides of various Proteus species, which provide the basis for classifying Proteus strains to O-serogroups. The antigenic relationships of Proteus strains within and beyond the genus as well as their O-antigen-related bioactivities are also discussed. PMID- 20305037 TI - Strategies to promote translational research within the European Organisation for Research and Treatment of Cancer (EORTC) Head and Neck Cancer Group: a report from the Translational Research Subcommittee. AB - Head and neck squamous cell cancer (HNSCC) is the sixth leading cause of cancer related deaths worldwide. These tumors are commonly diagnosed at advanced stages and mortality rates remain high. Even cured patients suffer the consequences of aggressive treatment that includes surgery, chemotherapy, and radiotherapy. In the past, in clinical trials, HNSCC was considered as a single disease entity. Advances in molecular biology with the development of genomic and proteomic approaches have demonstrated distinct prognostic HNSCC patient subsets beyond those defined by traditional clinical-pathological factors such as tumor subsite and stage [Cho W (ed). An Omics Perspective on Cancer Research. New York/Berlin: Springer 2010]. Validation of these biomarkers in large prospective clinical trials is required before their clinical implementation. To promote this research, the European Organisation for Research and Treatment of Cancer (EORTC) Head and Neck Cancer Program will develop the following strategies-(i) biobanking: prospective tissue collection from uniformly treated patients in the setting of clinical trials; (ii) a group of physicians, physician-scientists, and EORTC Headquarters staff devoted to patient-oriented head and neck cancer research; (iii) a collaboration between the basic scientists of the Translational Research Division interested in head and neck cancer research and the physicians of the Head and Neck Cancer Group; and (iv) funding through the EORTC Grant Program and the Network Core Institutions Consortium. In the present report, we summarize our strategic plans to promote head and neck cancer research within the EORTC framework. PMID- 20305039 TI - Pretreatment with lipopolysaccharide modulates innate immunity in corneal fibroblasts challenged with Aspergillus fumigatus. AB - Aspergillus fumigatus triggers inflammatory responses through Toll-like receptors (TLRs), particularly TLR2 and TLR4. In this study, we tested the hypothesis that lipopolysaccharide (LPS), a ligand of TLR4, can induce tolerance of A. fumigatus hyphae in telomerase-immortalized human stroma fibroblasts (THSFs). The THSFs were pretreated with low-dose LPS for various times and then challenged with A. fumigatus hyphae. We observed that pretreatment of THSFs with low-dose LPS resulted in diminished production of cytokines IL-8 and IL-6 and elevated expression of antimicrobial peptides, such as CC chemokine-ligand 20 (CCL20) and thymosin beta4 (Tbeta4), upon subsequent A. fumigatus challenge. Furthermore, LPS pretreatment also resulted in suppression of polymorphonuclear leukocyte (PMN) migration. Our results suggested that THSFs pretreated with LPS develop a state of A. fumigatus hyphae tolerance. This may induce protective mechanisms during fungal keratitis to prevent an excessive inflammatory response and to control infection of the cornea. PMID- 20305040 TI - Effects of alcohol on attention orienting and dual-task performance during simulated driving: an event-related potential study. AB - Driving is a complex task and is susceptible to inattention and distraction. Moreover, alcohol has a detrimental effect on driving performance, possibly due to alcohol-induced attention deficits. The aim of the present study was to assess the effects of alcohol on simulated driving performance and attention orienting and allocation, as assessed by event-related potentials (ERPs). Thirty-two participants completed two test runs in the Divided Attention Steering Simulator (DASS) with blood alcohol concentrations (BACs) of 0.00%, 0.02%, 0.05%, 0.08% and 0.10%. Sixteen participants performed the second DASS test run with a passive auditory oddball to assess alcohol effects on involuntary attention shifting. Sixteen other participants performed the second DASS test run with an active auditory oddball to assess alcohol effects on dual-task performance and active attention allocation. Dose-dependent impairments were found for reaction times, the number of misses and steering error, even more so in dual-task conditions, especially in the active oddball group. ERP amplitudes to novel irrelevant events were also attenuated in a dose-dependent manner. The P3b amplitude to deviant target stimuli decreased with blood alcohol concentration only in the dual-task condition. It is concluded that alcohol increases distractibility and interference from secondary task stimuli, as well as reduces attentional capacity and dual-task integrality. PMID- 20305041 TI - Novel protective mechanisms of antidepressants against 3-nitropropionic acid induced Huntington's-like symptoms: a comparative study. AB - Huntington's disease (HD) is characterized by progressive degeneration of neurons in the striatum, cortex and other parts of the brain, causing motor and cognitive dysfunction. 3-Nitropropionic acid (3-NP) is a well-known mycotoxin that significantly induces motor dysfunction in animals. Studies suggested the involvement of oxidative stress and nitric oxide mechanisms in HD pathogenesis. Clinical reports have also indicated the neuroprotective potential of antidepressants. Therefore, the present study has been designed to elucidate and compare the mechanistic role of different antidepressants (sertraline, venlafaxine, imipramine and trazodone) and their interaction with nitric oxide modulators if any, against 3-NP-induced neurotoxicity. Systemic 3-NP (10 mg/kg) administration for 14 days significantly reduced locomotor activity, body weight, motor coordination, oxidative defense and impaired mitochondrial complex enzyme activities in the striatum. Sertraline, venlafaxine, imipramine and trazodone treatments significantly improved behavioral, oxidative defense and mitochondrial complex enzyme activities as compared with the 3-NP-treated group. Systemic L arginine (50 mg/kg) pretreatment with sub-effective dose of sertraline (10 mg/kg), venlafaxine (10 mg/kg), imipramine (10 mg/kg) and trazodone (10 mg/kg) for 14 days significantly attenuated their protective effect. Similarly, L-nitro arginine methyl ester (L-NAME) (10 mg/kg) pretreatment with sub-effective dose of sertraline (10 mg/kg), venlafaxine (10 mg/kg), imipramine (10 mg/kg) and trazodone (10 mg/kg) for 14 days significantly potentiated their protective effects which were significant as compared with their effect alone, respectively. The results of the present study suggest that a nitric oxide mechanism might be involved in their protective effect against 3-NP-induced neurotoxicity. PMID- 20305042 TI - The triple reuptake inhibitor DOV216,303 exhibits limited antidepressant-like properties in the differential reinforcement of low-rate 72-second responding assay, likely due to dopamine reuptake inhibition. AB - There is a need for antidepressants with novel mechanisms of action. One approach has been to develop compounds that inhibit reuptake of all three monoamines in the central nervous system, for example DOV216,303. Differential reinforcement of low-rate (72-s) responding is a behavioral test that is predictive of antidepressant-like properties. The effects of antidepressant compounds belonging to multiple classes, the anxiolytic diazepam and the antipsychotic haloperidol, were assessed in the DRL-72s task. Subsequently, the antidepressant-like properties of acute DOV216,303 were assessed. The selective serotonin reuptake inhibitor fluvoxamine, the preferential norepinephrine reuptake inhibitor desipramine and the tricyclic antidepressant imipramine exhibited antidepressant like properties in the DRL-72s task. The atypical antidepressant bupropion, which inhibits dopamine and norepinephrine reuptake, and the selective dopamine transporter inhibitor GBR12909, changed reinforcement and response rates and inter-response time distribution in an opposite direction compared with the antidepressant compounds tested. The antipsychotic haloperidol exhibited antidepressant-like properties by increasing reinforcement rate, but failed to alter inter-response time distribution. Diazepam did not change reinforcement or response rates or inter-response time distribution. The triple reuptake inhibitor DOV216,303 significantly enhanced reinforcement rate at one intermediate dose, but exhibited similar effects as bupropion and GBR12909 on inter-response time distribution. The studies identified limited antidepressant-like properties of the triple reuptake inhibitor DOV216,303, likely due to dopamine transporter inhibition counteracting the effects of norepinephrine and serotonin transporter inhibition. PMID- 20305043 TI - The importance of the recognition of benign ethnic neutropenia in black patients during treatment with clozapine: case reports and database study. AB - Clozapine is the treatment of choice in refractory schizophrenia. Its more extensive use is limited by adverse effects and the need for regular blood monitoring. However, black patients are disadvantaged with respect to clozapine usage. Lower baseline Absolute Neutrophil Count compared with Whites leads to a greater frequency of blood testing, treatment interruptions and discontinuation. This may in part be explained by Benign Ethnic Neutropenia, but too few black patients are thus registered. The four cases described in this report underline some of the difficulties if this problem is under-recognized. Moreover, in our sample of 191 clozapine recipients in an inner London hospital, black patients account for approximately half, but only a small proportion, 8/95 (8.4%) are registered as having Benign Ethnic Neutropenia. None of the Benign Ethnic Neutropenia-registered patients discontinued treatment for haematological reasons. To optimize clozapine treatment and improve long-term outcomes, a significantly greater proportion of Black patients should be registered as having Benign Ethnic Neutropenia. PMID- 20305044 TI - Palliative care for people severely affected by multiple sclerosis: evaluation of a novel palliative care service. AB - Multiple sclerosis results in both physical and psychological disability but some patients have needs that are not adequately met by existing services. Our objective was to explore whether a new palliative care service improved outcomes for people severely affected by multiple sclerosis. A delayed intervention randomized controlled trial was undertaken with multiple sclerosis patients deemed by staff to have palliative care needs. The intervention was a multiprofessional palliative care team assessment and follow-up. The intervention group was offered the team immediately (fast track, FI); the control group continued best standard care and then offered the team after 3 months (standard intervention, SI). The main outcome measures were: patient reported issues using the Palliative Care Outcome Scale and Multiple Sclerosis Impact Scale at 12 weeks and caregiver burden using the Zarit Burden Inventory. Sixty-nine people were referred to the service; 52 consented or were eligible to be randomized (26 to the FI and 26 to the SI groups). At 12 weeks people in the FI group had an improvement (mean change -1.0) in the total score of 5 key symptoms whereas there was deterioration in the SI group (mean change 1.1, F = 4.75, p = 0.035). There was no difference in the change in general Palliative Care Outcome Scale or Multiple Sclerosis Impact Scale scores. There was an improvement in caregiver burden in the FI group and a deterioration in the SI group (F = 7.60, p = 0.013). Involvement with the palliative care service appeared to positively affect some key symptoms and reduced informal caregiver burden. PMID- 20305045 TI - Isolated pyuria in systemic lupus erythematosus. AB - The objective of this study was to assess isolated pyuria in an unselected systemic lupus erythematosus sample, and to determine factors potentially associated with this manifestation. We studied patients followed in our lupus clinic, defining isolated pyuria as more than 10 white blood cells per high power field in the absence of hematuria, proteinuria, casts, or bacteriuria. We assessed the effects of various demographic and clinical factors on the occurrence of isolated pyuria, using univariate logistic regression analyses. We also performed multivariate models which included sex, age, race/ethnicity, systemic lupus erythematosus duration, non-renal systemic lupus erythematosus disease activity, systemic lupus erythematosus damage, number of non-renal and renal American College of Rheumatology criteria ever present, pre-existing hypertension, and current drug exposures. Of 264 subjects, 66 were excluded (43 had bacteriuria or a contaminated urine culture and 23 had no concomitant urine culture); 27 of the remaining 198 (13.6%) had isolated pyuria. Sixteen of 27 patients with sterile pyuria had previous American College of Rheumatology criteria for renal involvement (hematuria, casts, and/or proteinuria) compared to 62/171 patients without sterile pyuria (unadjusted odds ratio = 2.55; 95% confidence interval = 1.11-5.85). Our univariate analyses also suggested a trend towards higher non-renal disease activity in patients with isolated pyuria. Independent associations were not evident in adjusted analyses. Isolated pyuria was observed in a significant number of our systemic lupus erythematosus sample. Although the differential diagnosis for isolated pyuria is broad, this manifestation may be correlated with lupus activity even in the absence of hematuria or proteinuria. Lupus (2010) 19, 793-796. PMID- 20305047 TI - Life and times with Friedrich Wegener. PMID- 20305046 TI - Association of estrogen and aromatase gene polymorphisms with systemic lupus erythematosus. AB - Experimental and animal studies suggested that estrogens play an important role in the development of systemic lupus erythematosus (SLE) through a variety of mechanisms involved in the regulation of the immune system. The objective of this study was to investigate the association between genetic variations in estrogen metabolic pathway genes, including estrogen receptor alpha (ESR1), estrogen receptor beta (ESR2), and aromatase (CYP19A1), and risk of SLE. We performed a genetic study of SLE among 46 medical record-confirmed female SLE cases and 102 female controls participating in an Internet-based case-control study of SLE. Polymorphisms analysed included: ESR1 PvuII, XbaI, and GT repeat; ESR2 RsaI, AluI, and CA repeat; and CYP19A1 RsaI, SfaN1, and TTTA repeat. We found significant association of the ESR1 PvuII (PP vs. pp, odds ratio (OR): 3.1, 95% confidence interval (CI): 1.1-9.3) and XbaI (XX vs. xx, adjusted OR: 3.4, 95% CI: 1.1-10.5) with SLE. Carrying the PPXX genotype conferred the highest risk (PPXX vs. ppxx, OR: 4.6, 95% CI: 1.3-15.9). We also found an association of SLE with the ESR2 CA repeat (SS vs. LL, OR: 2.8, 95% CI: 1.0-8.0). Our results support a role of estrogen in pathogenesis of SLE and suggested that genetic variants in the estrogen receptor genes might influence susceptibility. PMID- 20305048 TI - Serum 25-hydroxyvitamin D levels in patients with cutaneous lupus erythematosus in a Mediterranean region. AB - Low vitamin D levels have been found in patients with autoimmune diseases, including type I diabetes, rheumatoid arthritis, multiple sclerosis and systemic lupus erythematosus. The main source of vitamin D is exposure to sunlight, but the same solar radiation is known to exacerbate lupus erythematosus. We investigated the prevalence of vitamin D insufficiency in patients with cutaneous lupus erythematosus (CLE). We designed a cross-sectional study including 55 patients with CLE to measure their serum 25-hydroxyvitamin D (25(OH)D) by chemiluminescence immunoassay and compare it with a control group consisting of 37 healthy sex and age-matched subjects recruited from the patients' relatives as well as healthcare workers. Correlations with clinical and demographic variables were determined. Approximately 95% of patients with CLE had less than 30 ng/ml of serum 25(OH)D, which is accepted as the lower limit for vitamin D adequacy. Mean serum vitamin D values were significantly lower than controls (p = 0.038) and were associated with higher levels of parathyroid hormone (p = 0.050). A history of CLE was a strong predictor of insufficiency of vitamin D (odds ratio 4.2; 95% confidence interval 1.0-17.4). The results suggest a role of CLE in the metabolism of the vitamin and provide guidance for future studies looking at a potential role for vitamin D in the prevention and treatment of CLE. Lupus (2010) 19, 810-814. PMID- 20305049 TI - Long-term outcome of transtrochanteric anterior rotational osteotomy for osteonecrosis of the femoral head in patients with systemic lupus erythematosus. AB - This study sought to examine the long-term outcomes of transtrochanteric anterior rotational osteotomy (ARO) as treatment for osteonecrosis of the femoral head (ONFH) in patients with systemic lupus erythematosus (SLE). Twenty-one patients (33 hips), aged 20-40 years, underwent ARO between 1980 and 1988. We examined 16 patients (25 hips), a 76% follow-up rate. A Kaplan-Meier curve was used for survivorship analysis. Patients with surviving hips were evaluated by the modified Oxford hip score and Short Form 36 (SF-36). Twelve hips in eight patients had survived at the final follow-up. The average length of hip survival was 24.6 years (range: 20.1-27.2 years). Three patients (six hips) had died of unrelated causes without any subsequent operation. Based on Kaplan-Meier analysis with the endpoint defined as the need for a subsequent operation, the hip survival rate at 25 years was 73.7% (95% confidence interval, +/-19.8%). Based on classification by the modified Oxford hip score, five hips were classified as excellent, two hips were good, and the remaining five hips were fair. The average SF-36 summary score for the physical and mental components was 38.7 and 47.2 points, respectively. The physical component summary scores for three patients exceeded the normal level of the Japanese population. Lupus (2010) 19, 860-865. PMID- 20305050 TI - False-positive IgM for CMV in pregnant women with autoimmune disease: a novel prognostic factor for poor pregnancy outcome. AB - Our aims were to assess the frequency of false-positive IgM antibodies for cytomegalovirus in pregnant women with autoimmune diseases and in healthy women (controls) and to determine their relationship with pregnancy outcome. Data from 133 pregnancies in 118 patients with autoimmune diseases and from 222 pregnancies in 198 controls were assessed. When positive IgM for cytomegalovirus was detected, IgG avidity, cytomegalovirus isolation and polymerase chain reaction for CMV-DNA in maternal urine and amniotic fluid samples were performed in order to identify primary infection or false positivity. A statistically significantly higher rate of false-positive IgM was found in pregnancies with autoimmune diseases (16.5%) in comparison with controls (0.9%). A worse pregnancy outcome was observed among patients with autoimmune disease and false cytomegalovirus IgM in comparison with those without false positivity: earlier week of delivery (p = 0.017), lower neonatal birth weight (p = 0.0004) and neonatal birth weight percentile (p = 0.002), higher rate of intrauterine growth restriction (p = 0.02) and babies weighing less than 2000 g (p = 0.025) were encountered. The presence of false cytomegalovirus IgM in patients with autoimmune diseases could be used as a novel prognostic index of poor pregnancy outcome: it may reflect a non specific activation of the immune system that could negatively affect pregnancy outcome. Lupus (2010) 19, 844-849. PMID- 20305051 TI - Cadmium concentration in muscle, liver and kidney of sheep slaughtered in Falavarjan abattoir, Iran. AB - The aim of the present study was to investigate the levels of cadmium in sheep's muscle, liver and kidney from Isfahan and also to compare them with the levels reported in several other countries and with the maximum tolerance levels for the human consumption. The samples of muscle, liver and kidney of 60 animals around 1 to 6 years old were collected from the carcasses slaughtered in Flavarjan abattoir, Isfahan. Samples (acid digested and cadmium concentrations) were determined by graphite furnace atomic absorption spectrophotometry (GFAAS). The mean fresh weight concentrations in muscle, liver and kidney were about 0.0017 mg/kg, 0.0743 mg/kg and 0.02290 mg/kg, respectively. The mean concentration of cadmium in tissue samples was generally lower than the maximum acceptable concentration in European Commission (EC). Statistical analysis revealed a significant difference in cadmium concentration of liver and kidney between various age groups (p < 0.05). PMID- 20305052 TI - Is it possible to antagonize 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin- induced cleft palate by prenatal administration of folic acid? An experimental study. AB - 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) can cause a high percentage of cleft palate in fetuses when administered during organogenesis in certain strains of mice including C57BL/6J. In this study, folic acid (FA) was tested for antiteratogenic effects on TCDD-induced cleft palate in fetal mice. The pregnant C57BL/6J mice were dosed with 24 microg TCDD/kg and/or 5 mg, 10 mg, 20 mg, 40 mg FA/kg body weight on gestation day (GD) 10. The control group mice received 50 mL sesame oil/kg body weight on GD10. The mice were sacrificed on GD12.5, GD13.5, GD14.5, GD15.5, and GD16.5. The harvested embryos were examined to detect the incidence of cleft palate and the developing palatal shelves on different phases were investigated morphologically and histologically among different groups. Total frequency of clefts was 55.56% in TCDD group and 17.50% (5 mg), 42.85% (10 mg), 42.10% (20 mg), 28.26% (40 mg) in TCDD + FA groups. FA (5 mg) reduced the incidence of the cleft palate from 55.56% to 17.50% (p = 0.005). There were no significant differences between the TCDD group and 10 mg, 20 mg, 40 mg TCDD + FA groups. Based on the these results, the present study suggests that FA can reduce the incidence of 2,3,7,8-TCDD-induced cleft palate in mice. PMID- 20305053 TI - Long-term follow-up of 24.5 years after intra-articular anterior cruciate ligament reconstruction with lateral extra-articular augmentation. AB - BACKGROUND: Many studies have reported successful outcomes 10 to 15 years after ACL reconstruction. However, few authors report results at ultra long-term follow up (more than 20 years of follow-up). PURPOSE: The aim of this study was to determine how the status of the medial meniscus and the medial compartment articular cartilage observed at the time of ACL reconstruction affects results more than 24 years after surgery. This article examines long-term outcome of ACL reconstruction with extra-articular augmentation (procedure performed through a medial arthrotomy). STUDY DESIGN: Case series; Level of evidence, 4. METHODS: One hundred of 148 patients reviewed at 11.5 years of follow-up could be reviewed at 24.5 years. Complete clinical and radiographic evaluation (International Knee Documentation Committee scale and Knee Injury and Osteoarthritis Outcome Score) was performed. RESULTS: The radiographic International Knee Documentation Committee rating was as follows: grade A, 39%; grade B, 7%; grade C, 27%; and grade D, 27%. Onset of osteoarthritis was correlated with medial meniscal status and femoral chondral defects at time of surgery. CONCLUSION: Total medial meniscectomy and articular cartilage damage were risk factors for osteoarthritis. PMID- 20305054 TI - Variation of the intermaxillary tooth-size relationship in normal occlusion. AB - The purpose of this study was to explore the intermaxillary tooth-size relationship that is attributed to normal occlusion using multivariate cluster analysis, while simultaneously incorporating the full dentition as a data set. From the central incisor to the second molar, the tooth sizes of 307 subjects (188 males and 119 females; mean age +/- standard deviation, 19.9 +/- 3.3 years) with normal occlusion were investigated. Tooth-size data were analysed separately for the maxilla and the mandible. When clustering, the partitioning around medoids (PAM) algorithm was performed with the transformed data based on principal component analysis (PCA). After the subjects were classified into four groups, the cluster memberships were cross-classified, and the distribution pattern and intermaxillary tooth-size relationships were explored. Bolton tooth ratio showed a relatively wide range, and this was indicative of the variability in tooth size in subjects with a normal occlusion. However, the patterns of the intermaxillary tooth-size relationship were similar for males and females, and this result was concordant with the findings of the classic Bolton analysis. Using the multivariate approach to analyse the tooth-size data set of an individual patient and then comparing the results with the normal occlusion cluster has possible clinical applications in determining the amount and location of tooth-size control in orthodontics. PMID- 20305055 TI - Cephalometric evaluation of children with nocturnal sleep-disordered breathing. AB - The present study aimed to assess the cephalometric features in children with sleep-disordered breathing (SDB). The subjects were 70 children (34 boys and 36 girls, mean age 7.3, SD 1.72, range 4.2-11.9 years) with habitual snoring and symptoms of obstructive sleep disorder for more than 6 months. On the basis of overnight polygraphic findings, the subjects were further divided into subgroups of 26 children with diagnosed obstructive sleep apnoea (OSA), 17 with signs of upper airway resistance syndrome (UARS), and 27 with snoring. A control group of 70 non-obstructed children matched for age and gender was selected. Lateral skull radiographs were taken and cephalograms were traced and measured. The differences between the matched groups were studied using t-test for paired samples. Differences between the subgroups were studied using analysis of variance followed by Duncan's multiple comparison method. Children with SDB were characterized by an increased antero-posterior jaw relationship (P = 0.001), increased mandibular inclination in relation to the palatal line (P = 0.01), increased total (P = 0.019) and lower (P = 0.005) anterior face heights, a longer (P = 0.018) and thicker (P = 0.002) soft palate, smaller airway diameters at multiple levels of the naso- and oropharynx, larger oropharyngeal airway diameter at the level of the base of the tongue (P = 0.011), lower hyoid bone position (P = 0.000), and larger craniocervical angles (NSL-CVT, P = 0.014; NSL-OPT, P = 0.023) when compared with the non-obstructed controls. When divided into subgroups according to the severity of the disorder, OSA children deviated significantly from the control children especially in the oropharyngeal variables. Children with UARS and snoring also deviated from the controls, but the obstructed subgroups were not confidently distinguishable from each other by cephalometric measurements. Logistic regression analysis indicated that UARS and OSA were associated with decreased pharyngeal diameters at the levels of the adenoids (PNS-ad1) and tip of the uvula (u1-u2), an increased diameter at the level of the base of the tongue (rl1-rl2), a thicker soft palate, and anteriorly positioned maxilla in relation to the cranial base. Lateral cephalogram may thus reveal important predictors for SDB in children. Attention should be paid to pharyngeal measurements. Systematic orthodontic evaluation of SDB children is needed because of the effects of obstructed sleep on the developing craniofacial skeleton. PMID- 20305056 TI - A new concept for the cephalometric evaluation of craniofacial patterns (multiharmony). AB - Orthodontists commonly specify the alignment of the teeth and jaws by means of a set of k angles and their relationship with each other. Each individual can thus be visualized as a point in k-dimensional space. Individuals regarded as having an ideal occlusion and well-balanced face, form a cloud of points that is termed the 'norm' population. Individuals far from the cloud require orthodontic intervention. In this study, a method is presented--the multiharmony method (MHM), which assists in treatment planning. With multiple regression analysis, the expected value that each angle should take in a norm individual when the remaining angles are given is estimated. The residual difference between the measured angle and its expected value then indicates the deviation from a harmonic appearance in the respective angle. The MHM was applied to a data set of 134 Korean individuals identified as the norm population (Class I, mean age: 19.6 years) and to 87 patients (Class III, mean age: 21.2 years). From the number and size of the residuals, the two populations could be separated almost completely. Almost all patients showed residuals larger than any residual in the norm population (sensitivity: 99 per cent), whereas 90 per cent of all norm individuals showed no extreme residuals. The MHM can also be used to assist in visualizing different treatment effects, thereby assisting the orthodontist in choosing the best course of treatment for each patient. PMID- 20305057 TI - Randomized, double-blind, placebo-controlled, single intravenous dose-escalation study to evaluate the safety, tolerability, and pharmacokinetics of the novel coronary smooth muscle cell proliferation inhibitor Biolimus A9 in healthy individuals. AB - Biolimus A9 (BA9) is a novel proliferation inhibitor of coronary smooth muscle cells that has been specifically designed for coating drug-eluting stents. The goals of this study were to identify the highest safe intravenous dose of BA9, to evaluate the dose-dependent pharmacokinetics of BA9 after intravenous administration in humans, and to characterize early clinical symptoms of BA9 toxicity in healthy subjects. This phase 1 trial in healthy subjects was designed as a double-blind, placebo-controlled, randomized, ascending single-dose study. After screening and randomization, 28 volunteers received either placebo (n = 7) or BA9 (n = 21) in a double-blinded fashion. Doses from 0.0075 mg/kg were escalated to 0.25 mg/kg in 4 cohorts. BA9 concentrations were measured using liquid chromatography-tandem mass spectrometry. BA9 doses up to 0.075 mg/kg were well tolerated. Only the highest BA9 dose of 0.25 mg/kg produced reversible drug related adverse events. The most frequent adverse events were headache, nausea, and mouth ulcers, most likely due to immunosuppression. Exposure to BA9 did not result in electrocardiographic or clinical laboratory changes. BA9 had a terminal half-life of 90.0 +/- 40.0 hours (all n = 21, mean +/- standard deviation), an apparent clearance from blood of 0.96 +/- 1.07 L/kg/h, and a volume of distribution of 96.5 +/- 72.6 L/kg. PMID- 20305058 TI - Dyella thiooxydans sp. nov., a facultatively chemolithotrophic, thiosulfate oxidizing bacterium isolated from rhizosphere soil of sunflower (Helianthus annuus L.). AB - A Gram-negative, aerobic, motile, rod-shaped, thiosulfate-oxidizing bacterium, designated ATSB10(T), was isolated from rhizosphere soil of sunflower (Helianthus annuus L.). Phylogenetic analysis based on 16S rRNA gene sequences revealed that strain ATSB10(T) was closely related to members of the genera Dyella (96.4-98.1 % 16S rRNA gene sequence similarity) and Luteibacter (96.4-97.0 %) and Fulvimonas soli LMG 19981(T) (96.7 %) and Frateuria aurantia IFO 3245(T) (97.8 %). The predominant fatty acids were iso-C(16 : 0), iso-C(17 : 1)omega9c and iso-C(15 : 0). The major quinone was Q-8. The G+C content of the genomic DNA was 66.0 mol%. The major polar lipids were diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, phosphatidyldimethylethanolamine, an unknown phospholipid, unknown aminophospholipids and an unknown aminolipid. On the basis of phenotypic properties, phylogenetic distinctiveness and DNA-DNA relatedness, strain ATSB10(T) represents a novel species in the genus Dyella, for which the name Dyella thiooxydans sp. nov. is proposed. The type strain is ATSB10(T) (=KACC 12756(T) =LMG 24673(T)). PMID- 20305059 TI - Microbacterium mitrae sp. nov., isolated from salted turban shell. AB - A novel bacterium (strain M4-8(T)) belonging to the genus Microbacterium was isolated from salted turban shell, which is a traditional fermented food in Korea. Its morphology, physiology, biochemical features and 16S rRNA gene sequence were characterized. Cells of this strain were Gram-positive, non-motile, non-spore-forming rods that formed yellow-pigmented colonies. It grew in 0-8 % (w/v) NaCl and at 15-37 degrees C, with optimal growth occurring in 1 % (w/v) NaCl and at 30 degrees C. Phylogenetic analysis based on 16S rRNA gene sequences indicated that strain M4-8(T) is associated with members of the genus Microbacterium. Within the phylogenetic tree, this novel strain shared a branching point with Microbacterium hominis IFO 15708(T) (97.8 % similarity). The DNA G+C content was 71.3 mol% and DNA-DNA hybridization experiments showed a low level (<29 %) of DNA-DNA relatedness between M4-8(T) and its closest relatives. The major fatty acids were iso-C(15 : 0) and anteiso-C(15 : 0) and the major cell wall diamino acid was ornithine. Data obtained from DNA-DNA hybridization and chemotaxonomic phenotypic analysis support the conclusion that strain M4-8(T) represents a novel species within the genus Microbacterium. The name Microbacterium mitrae sp. nov. is proposed, with M4-8(T) (=KACC 21129(T) =JCM 16363(T)) as the type strain. PMID- 20305060 TI - Description of Undibacterium oligocarboniphilum sp. nov., isolated from purified water, and Undibacterium pigrum strain CCUG 49012 as the type strain of Undibacterium parvum sp. nov., and emended descriptions of the genus Undibacterium and the species Undibacterium pigrum. AB - A Gram-negative, oxidase- and catalase-positive, flagellated, rod-shaped bacterium, designated strain EM 1(T), was isolated from purified water. 16S rRNA gene sequence analysis indicated that the novel strain belonged to the family Oxalobacteraceae within the class Betaproteobacteria; the closest phylogenetic relative was Undibacterium pigrum DSM 19792(T) (96.7 % gene sequence similarity). The new isolate could be distinguished from the type strain of U. pigrum DSM 19792(T) (=CCUG 49009(T)=CIP 109318(T)) and from strain CCUG 49012(T), which has been described as a second genomovar of this species, on the basis of genotypic data and several phenotypic properties. An S-layer was present in the cell envelope in U. pigrum DSM 19792(T), but was absent in strains EM 1(T) and CCUG 49012(T). Test conditions were established that enabled strain CCUG 49012(T) to be distinguished from U. pigrum DSM 19792(T). As found for U. pigrum, the main fatty acids of strains EM 1(T) and CCUG 49012(T) were summed feature 3 (including unsaturated C(16 : 1)omega7c), straight-chain C(16 : 0) and unsaturated C(18 : 1)omega7c (low percentage in strain CCUG 49012(T)), and C(10 : 0) 3-OH was the sole hydroxylated fatty acid. The polar lipid profile consisted of the predominant lipids phosphatidylethanolamine, diphosphatidylglycerol and phosphatidylglycerol. The polyamine profile was mainly composed of the major compound putrescine and moderate amounts of 2-hydroxyputrescine. In contrast to U. pigrum and strain CCUG 49012(T), where ubiquinone Q8 was reported as the sole quinone component, the quinone system of strain EM 1(T) consisted of ubiquinone Q 8 (64 %) and Q-7 (36 %). The 16S rRNA gene sequence similarity, the polar lipid profile and the absence of C(12)-hydroxylated fatty acids all indicated that strain EM 1(T) was affiliated with the genus Undibacterium. 16S rRNA gene sequence similarity values lower than 97.0 % and several differentiating phenotypic traits demonstrated that strain EM 1(T) represents a novel species for which the name Undibacterium oligocarboniphilum sp. nov. is proposed (type strain EM 1(T)=DSM 21777(T)=CCUG 57265(T)). In addition, based on previously published results and this study, a separate species, Undibacterium parvum sp. nov., is proposed with strain CCUG 49012(T) (=DSM 23061(T)=CIP 109317(T)) as the type strain. PMID- 20305061 TI - Fontibacillus panacisegetis sp. nov., isolated from soil of a ginseng field. AB - A facultatively anaerobic, endospore-forming bacterium, designated strain P11 6(T), was isolated from soil of a ginseng field located in Geumsan County, Republic of Korea. Cells of strain P11-6(T) were Gram-stain-negative, catalase negative, motile rods and produced semi-translucent, circular, white colonies on tryptic soy agar. The isolate contained MK-7 as the only menaquinone and anteiso C(15 : 0) as the major fatty acid. Diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, an unknown aminophosphoglycolipid, an unknown aminophospholipid, two unknown phospholipids, three unknown glycolipids and three unknown lipids were detected in the polar lipid profile. The DNA G+C content of strain P11-6(T) was 41.9 mol%. Phylogenetic analysis based on 16S rRNA gene sequencing showed that strain P11-6(T) was most closely related to Fontibacillus aquaticus GPTSA 19(T) (97.2 % sequence similarity) and that it formed a separate lineage with F. aquaticus in the family Paenibacillaceae. Combined phenotypic and DNA-DNA hybridization data supported the conclusion that strain P11-6(T) represents a novel species in the genus Fontibacillus, for which the name Fontibacillus panacisegetis sp. nov. is proposed; the type strain is P11-6(T) (=KCTC 13564(T) =CECT 7605(T)). PMID- 20305063 TI - Oleibacter marinus gen. nov., sp. nov., a bacterium that degrades petroleum aliphatic hydrocarbons in a tropical marine environment. AB - Three Gram-negative, motile, mesophilic, aerobic, rod-shaped bacterial strains, designated 2O1(T), 1O14 and 1O18, were isolated from Indonesian seawater after enrichment with crude oil and a continuous supply of supplemented seawater. The strains exhibited high n-alkane-degrading activity, which indicated that the strains were important degraders of petroleum aliphatic hydrocarbons in tropical marine environments. Phylogenetic analyses based on 16S rRNA gene sequences of members of the Gammaproteobacteria showed that the isolates formed a coherent and distinct cluster in a stable lineage containing Oceanobacter kriegii IFO 15467(T) (96.4-96.5 % 16S rRNA gene sequence similarity) and Thalassolituus oleivorans MIL 1(T). DNA G +C content was 53.0-53.1 mol%. The major fatty acids were C(16 : 0), C(16 : 1)omega7 and C(18 : 1)omega9 and the hydroxy fatty acids were C(12 : 0) 3 OH and C(10 : 0) 3-OH. The polar lipids were phosphatidylglycerol, a ninhydrin positive phospholipid(s) and glycolipids. The major quinone was Q-9 (97-99 %), which distinguished the isolates from Oceanobacter kriegii NBRC 15467(T) (Q-8; 91 %). On the basis of phenotypic, genotypic and chemotaxonomic data, including DNA DNA hybridization, the isolates represent a novel genus and species, for which the name Oleibacter marinus gen. nov., sp. nov. is proposed. The type strain of Oleibacter marinus is 2O1(T) (=NBRC 105760(T) =BTCC B-675(T)). PMID- 20305062 TI - Borrelia carolinensis sp. nov., a novel species of the Borrelia burgdorferi sensu lato complex isolated from rodents and a tick from the south-eastern USA. AB - A group of 16 isolates with genotypic characteristics different from those of known species of the Borrelia burgdorferi sensu lato complex were cultured from ear biopsies of the rodents Peromyscus gossypinus and Neotoma floridana trapped at five localities in South Carolina, USA, and from the tick Ixodes minor feeding on N. floridana. Multilocus sequence analysis of members of the novel species, involving the 16S rRNA gene, the 5S-23S (rrf-rrl) intergenic spacer region and the flagellin, ospA and p66 genes, was conducted and published previously and was used to clarify the taxonomic status of the novel group of B. burgdorferi sensu lato isolates. Phylogenetic analysis based on concatenated sequences of the five analysed genomic loci showed that the 16 isolates clustered together but separately from other species in the B. burgdorferi sensu lato complex. The analysed group therefore represents a novel species, formally described here as Borrelia carolinensis sp. nov., with the type strain SCW-22(T) (=ATCC BAA-1773(T) =DSM 22119(T)). PMID- 20305064 TI - Vibrio communis sp. nov., isolated from the marine animals Mussismilia hispida, Phyllogorgia dilatata, Palythoa caribaeorum, Palythoa variabilis and Litopenaeus vannamei. AB - Eight Vibrio isolates originating from the marine corals Mussismilia hispida and Phyllogorgia dilatata and the zoanthids Palythoa caribaeorum and Palythoa variabilis in Brazil and the Pacific white shrimp (Litopenaeus vannamei) in Ecuador were studied by means of a polyphasic approach. The novel isolates formed a tight monophyletic group in the genus Vibrio and were closely related to species of the Vibrio harveyi group, to which they showed more than 99 % 16S rRNA gene sequence similarity. Analysis based on concatenated sequences of the following seven genes, 16S rRNA, gyrB, recA, rpoA, topA, pyrH and mreB (5633 bp in length), showed clear separation between the isolates and species of the V. harveyi group. Amplified fragment length polymorphism (AFLP) analysis, performed previously, revealed that a representative isolate of this group, LMG 20370, was clearly separate from known Vibrio species (it belonged to the so-called AFLP cluster A31). DNA-DNA hybridization (DDH) experiments with representative isolates and type strains of the V. harveyi species group revealed high DDH between the novel isolates (more than 74 %) and less than 70 % DDH towards type strains of related Vibrio species, proving the novel species status of the isolates. Phenotypically, the novel species belongs to the arginine dihydrolase (A)-negative, lysine decarboxylase (L)-positive and ornithine decarboxylase (O) positive (A-/L+/O+) cluster reported previously. Most species of the V. harveyi group (i.e. Vibrio rotiferianus, V. harveyi, V. parahaemolyticus and V. alginolyticus) also belong to this A-/L+/O+ cluster. However, several phenotypic features can be used for the identification of the novel species. In contrast to its closest phylogenetic neighbours, the novel species exhibits esterase (C4) and N-acetyl-beta-glucosaminidase activities, but it does not produce acetoin, does not use citrate, alpha-ketoglutaric acid or propionic acid and does not ferment melibiose. The novel species can also be differentiated on the basis of the presence of the fatty acids C(17 : 0,) C(17 : 1)omega8c, iso-C(17 : 0) and iso C(13 : 0) and the absence of the fatty acid C(18 : 0). The name Vibrio communis sp. nov. is proposed for this taxon. Strain R-40496(T) (=LMG 25430(T) =CAIM 1816(T)) is the type strain. PMID- 20305065 TI - Arcobacter trophiarum sp. nov., isolated from fattening pigs. AB - In the course of a longitudinal study elucidating the dynamics of Arcobacter populations in pigs, 16 isolates of Gram-reaction-negative, rod-shaped, slightly curved, non-spore-forming bacteria were grouped by amplified fragment length polymorphism analysis into a distinct phenon within the genus Arcobacter. Fragments were generated for all isolates in a genus-specific PCR assay, but no amplicon was obtained in a species-specific multiplex-PCR test. Numerical analysis of the whole-cell protein profiles also showed that all isolates clustered in a single group that was distinct from related members of the genus Arcobacter. DNA-DNA hybridizations between two representative strains, designated 64(T) and 122, of the isolates obtained exhibited a mean DNA-DNA relatedness of 72 %. DNA-DNA hybridizations between strains 64(T) and 122 and reference strains of other animal-related bacteria of the genus Arcobacter revealed binding values of 47 % or less. The DNA G+C contents of the two representative strains were 28.5 and 28.4 mol%, respectively, and analysis of three marker genes identified Arcobacter cryaerophilus, A. thereius, A. cibarius and A. skirrowii as their closest phylogenetic neighbours. Strains 64(T) and 122 could be distinguished from other members of the genus Arcobacter by means of biochemical tests for catalase and urease activities, nitrate reduction, indoxyl acetate hydrolysis, lack of growth at 37 degrees C, growth in 2 % (w/v) NaCl, growth on 0.1 % sodium deoxycholate and non-supplemented Campylobacter charcoal-deoxycholate base medium and resistance to cephalothin (32 mg l(-1)) and cefoperazone (64 mg l(-1)). Additionally, a PCR assay was developed for the detection and identification of strains 64(T) and 122, which represent a novel species of the genus Arcobacter, for which the name Arcobacter trophiarum sp. nov. is proposed. The type strain is strain 64(T) (=LMG 25534(T) =CCUG 59229(T)). PMID- 20305067 TI - Reclassification of 'Dactylosporangium variesporum' as Saccharothrix variisporea corrig. (ex Tomita et al. 1977) sp. nov., nom. rev. AB - In the course of a polyphasic study it was observed that 'Dactylosporangium variesporum' NRRL B-16296 is misclassified in the genus Dactylosporangium as it exhibits properties consistent with its assignment to the genus Saccharothrix. Phylogenetic analyses based on 16S rRNA gene sequences show that the strain falls within the evolutionary radiation of the genus Saccharothrix, a result which is supported by corresponding chemotaxonomic and morphological markers. The strain is phylogenetically most closely, albeit loosely, related to Saccharothrix espanaensis, but can be readily distinguished from this and other species of the genus Saccharothrix with validly described names by using a range of phenotypic properties. The combined genotypic and phenotypic data demonstrate conclusively that this strain should be classified as a new species in the genus Saccharothrix for which the name Saccharothrix variisporea sp. nov. is proposed. The type strain is NRRL B-16296(T) (=ATCC 31203(T) =DSM 43911(T) =JCM 3273(T) =NBRC 14104(T)). PMID- 20305068 TI - Correctional suicide: has progress ended? PMID- 20305066 TI - Micromonospora rhizosphaerae sp. nov., isolated from mangrove rhizosphere soil. AB - Strain 211018(T) was isolated from mangrove Excocaria agallocha rhizosphere soil. 16S rRNA gene sequence analysis showed the highest similarity to the type strains of Micromonospora olivasterospora DSM 43868(T) (98.6 %) and Micromonospora pattaloongensis TJ2-2(T) (98.4 %). gyrB gene sequence analysis also indicated that strain 211018(T) should be assigned to the genus Micromonospora. The characteristic whole-cell sugars are xylose, mannose and arabinose. The predominant menaquinone is MK-9(H(4)) and the major fatty acids are iso-C(15 : 0) (27.5 %), 10-methyl C(17 : 0) (14.2 %), C(17 : 1)omega8c (12.8 %), iso-C(16 : 0) (12.6 %), anteiso-C(15 : 0) (6.1 %), iso-C(17 : 0) (4.1 %) and anteiso-C(17 : 0) (4.0 %). The phospholipid profile comprises phosphatidylethanolamine, phosphatidylglycerol, phosphatidylinositol and phosphatidylinositol mannosides. The DNA G+C content is 70.8 mol%. The chemotaxonomic data of the strain coincided with those of the genus Micromonospora. Furthermore, a combination of DNA-DNA hybridization results and some physiological and biochemical properties indicated that the novel strain could be readily distinguished from the closest phylogenetic relatives. On the basis of these phenotypic and genotypic data, strain 211018(T) represents a novel species of the genus Micromonospora, for which the name Micromonospora rhizosphaerae sp. nov. is proposed. The type strain is 211018(T) (=CGMCC 4.5599(T) =DSM 45431(T)). PMID- 20305069 TI - The forensic risks of DSM-V and how to avoid them. PMID- 20305070 TI - The mental status examination in the age of the internet. AB - The Internet has grown increasingly relevant in the practice of forensic psychiatry. To a psychiatrist conducting a forensic evaluation, the evaluee's Internet use can be relevant in nearly all aspects of the analysis. An evaluee's Internet presence may help to confirm, corroborate, refute, or elaborate on the psychiatrist's general impression of the person. Questions about the individual's choice of screen names, activities, images, and phrases can be valuable conversational tools to increase candor and self-disclosure, even among less cooperative evaluees. Difficulties in mood or affect regulation, problems with thought process or content, and impaired impulse control may be apparent in the evaluee's behavior in various Internet forums-for example, hostile or provocative behavior in social forums or excessive use of gaming or shopping websites. Discussions about the evaluee's behavior on the Internet can help the psychiatrist to assess for impaired insight and judgment. Perceptual disturbances, such as derealization and depersonalization, may be related to an evaluee's overidentification with the virtual world to the neglect of real-life needs and responsibilities. Furthermore, digital evidence can be especially useful in assessments of impairment, credibility, and dangerousness or risk, particularly when the evaluee is uncooperative or unreliable in the face-to-face psychiatric examination. This discussion will provide illustrative examples and suggestions for questions and topics the forensic psychiatrist may find helpful in conducting a thorough evaluation in this new age of the Internet. PMID- 20305071 TI - Commentary: the mental status examination in the age of the internet--challenges and opportunities. AB - In her Presidential address, Dr. Recupero shows us how the Internet and changes in electronic communications have affected the forensic evaluation process in multiple ways. These developments provide the forensic psychiatrist with new tools and new sources of information, and their novelty brings about new challenges and opportunities. This commentary focuses on the use of information and communication technology (ICT) for purposes of obtaining collateral information in addition to a sample of other likely uses of ICT in the practice of forensic psychiatry. Collateral information from electronic communications such as e-mails, web postings, texting, and social networking sites provides useful data but also raises challenges in interpretation. Digital information about the expert can be used by cross-examining attorneys. Electronic tools can help the forensic psychiatrist to be more efficient. Correctional systems have a great deal to gain by adopting more efficient information systems. Continuing evolution of these technologies assures that we can expect more rapid change in these areas in the future. PMID- 20305072 TI - Conceptualizing the forensic psychiatry report as performative narrative. AB - Forensic psychiatry has evolved into a recognized specialty. Two core competencies, often overlooked but commonplace in forensic psychiatry, are the constructing of forensic reports and the presenting of oral testimony. This article concerns the written forensic report and conceptualizes it as performative writing. We first review the development of the forensic report's structure over the past 30 years or so and then apply constructs from other disciplines as we propose a process for creating narrative forensic reports. Such writing is grounded in the discipline of psychiatry, relies on ethics-based principles of respect for persons and truth-telling, and uses language to tell a story that persuades the legal audience. We examine the impact of voice, pitfalls to avoid, and the concepts of witnessing and labeling, as we describe the process of formulating the narrative through the voice of the forensic expert. PMID- 20305073 TI - Commentary: the art of forensic report writing. AB - As forensic psychiatry has matured into a well-recognized subspecialty, considerable agreement about the format and content of reports has emerged. Griffith et al. now turn their attention to the art of forensic writing. Their description of the forensic report as "performative narrative" may help to refine professional practice so long as the ethics-related pitfalls are identified and avoided. PMID- 20305074 TI - Commentary: conceptualizing the forensic psychiatry report. AB - Relatively little attention has been paid to training forensic evaluators to prepare expert reports. Griffith and colleagues, in two publications, argue for considering forensic report writing as a core competence in the field along with forensic evaluation and court testimony. They expand our conceptualization of report writing to consider the subjective component of report writing, revealing the evaluator's voice. Evaluators bring many identities, voices, and tactics to conducting their evaluations and preparing their expert reports. Evaluators do not simply recount their findings from the evaluation, but create a narrative that is inherently subjective, not purely objective or scientific. Their views should ring true for forensic evaluators at all levels of training and experience. Additional research and training regarding forensic report writing are needed. PMID- 20305075 TI - Forensic evaluations and mandated reporting of child abuse. AB - Statutes requiring physicians to report suspected cases of child abuse create a potential conflict for psychiatrists working in the forensic setting. What happens in the case in which a forensic psychiatrist, during the course of an evaluation requested by a defense attorney, learns about child abuse perpetrated by the evaluee? A complicated legal, ethics-related, and interpersonal dilemma emerges. Reporting the abuse may contribute directly to further legal harm to the evaluee and place a strain on the relationship with the attorney. However, not reporting the abuse potentially involves ignoring a legal mandate and risking further harm to a child. This article first reviews mandated reporting statutes across the states. Next, the arguments for and against reporting are outlined. Existing solutions to the problem are reviewed, and several alternative solutions are explored. Finally, an approach to negotiating the dilemma that can be used by forensic psychiatrists in practice is suggested. PMID- 20305076 TI - Commentary: Tarasoff duties arising from a forensic independent medical examination. AB - The question of whether a Tarasoff duty may emerge from a credible threat by an examinee during an independent medical examination has not been extensively addressed in the professional literature. This article analyzes that question and provides suggestions for how to respond to a perceived duty. PMID- 20305077 TI - Improbable predictions at capital sentencing: contrasting prison violence outcomes. AB - The postconviction prison disciplinary records of capital defendants (n = 73) who had been the subject of defense-sponsored violence risk assessments or risk related testimony (1995-2007) that asserted an improbability of future serious prison violence were analyzed. During postconviction prison tenures averaging 4.4 years, none of the capital defendants was cited for accomplished serious assaults. The prevalence of misconduct was inversely related to severity: 54.8 percent were cited for some disciplinary misconduct, 27.4 percent for potentially violent disciplinary violations, 12.3 percent for assaultive misconduct, and 1.4 percent for attempted serious assault. Rates of misconduct among the capital offenders were equivalent to those among all inmates (n = 18,561, annual average) in high-security federal prisons (2001-2005). The accuracy rate of forecasts of improbability stands in sharp contrast to that of prosecution-sponsored expert testimony at capital sentencing that had asserted high rates of future violence. PMID- 20305078 TI - Adolescent parricide as a clinical and legal problem. AB - Criminologists contribute to the knowledge regarding the continuing problem of parricide by way of macrostudies, utilizing large samples that reveal patterns of how such acts are carried out, gender differences, and other aspects. Clinicians have the opportunity to pursue microinvestigations into the details of how cognitive processes and emotions operate in the adolescent who engages in such behavior. Such investigations entail pursuing specifics in the psychosocial realm, such as earlier maltreatments and ongoing psychological conflicts, and also being alert to the neurobiological differences between adolescents and adults. The use of battered child syndrome as a legal defense is discussed, with contrasts made between relying on a posttraumatic stress disorder (PTSD) approach and a duress defense, based on explanations related to shame and humiliation. PMID- 20305080 TI - The "pseudocommando" mass murderer: part I, the psychology of revenge and obliteration. AB - The pseudocommando is a type of mass murderer who kills in public during the daytime, plans his offense well in advance, and comes prepared with a powerful arsenal of weapons. He has no escape planned and expects to be killed during the incident. Research suggests that the pseudocommando is driven by strong feelings of anger and resentment, flowing from beliefs about being persecuted or grossly mistreated. He views himself as carrying out a highly personal agenda of payback. Some mass murderers take special steps to send a final communication to the public or news media; these communications, to date, have received little detailed analysis. An offender's use of language may reveal important data about his state of mind, motivation, and psychopathology. Part I of this article reviews the research on the pseudocommando, as well as the psychology of revenge, with special attention to revenge fantasies. It is argued that revenge fantasies become the last refuge for the pseudocommando's mortally wounded self-esteem and ultimately enable him to commit mass murder-suicide. PMID- 20305079 TI - An empirical study of employment and disability over three years among survivors of major disasters. AB - This study was designed to clarify the relationship between exposure to disaster and future employment. Survivors of seven disasters and their employment histories were prospectively followed over three years. At the time of the disasters, 86 percent were working, and at follow-up, 84 percent were working. All of the 261 individuals employed on the day of the disaster described themselves as not disabled at follow-up, although one individual who dropped out of the workforce to become a self-described housewife shortly after the disaster and who developed PTSD may have left the workforce because of lasting emotional effects of the disaster. The reasons she provided for changing job status were not disaster related, however. Long-standing employment disability was virtually nonexistent in this highly exposed sample of trauma survivors, but it is possible that some cases of PTSD-related disability were lost to follow-up. Further work is needed to explore psychological disability in other trauma survivor populations. PMID- 20305081 TI - The Americans With Disabilities Act Amendments Act of 2008: implications for the forensic psychiatrist. AB - The Americans With Disabilities Act Amendments Act of 2008 (ADAAA) significantly modifies the 1990 Americans With Disabilities Act. As a result of this legislation, more Americans are likely to qualify as disabled and to be further protected from discrimination under the ADA. The ADAAA also effectively overturns key rulings in the U.S. Supreme Court cases of Sutton v. United Air Lines, Inc. and Toyota Motor Manufacturing v. Williams. This article summarizes important changes resulting from the ADAAA legislation that psychiatrists and psychologists must understand when evaluating ADA disability claims. PMID- 20305082 TI - Mentally ill persons who commit crimes: punishment or treatment? AB - In many countries, there continue to be conflicting opinions and mechanisms regarding the appropriateness of treatment and/or punishment for mentally ill individuals who commit crimes. The general population is concerned with public safety and often finds it difficult to accept the possibility that a mentally ill individual who commits a crime can be hospitalized and eventually discharged, sometimes after a relatively short time. In most countries the options of incarceration and hospitalization are available in concert. In some, incarceration occurs before hospitalization. In others, hospitalization is first, followed by a prison term. An additional option could be "treatment years." The court would determine the number of years of treatment required, according to the crime. This dilemma has no unequivocal solution. The goal is to reach a balance between the right of the patient to treatment and the responsibility of the courts to ensure public safety. PMID- 20305083 TI - Solitary confinement and mental illness in U.S. prisons: a challenge for medical ethics. AB - In recent years, prison officials have increasingly turned to solitary confinement as a way to manage difficult or dangerous prisoners. Many of the prisoners subjected to isolation, which can extend for years, have serious mental illness, and the conditions of solitary confinement can exacerbate their symptoms or provoke recurrence. Prison rules for isolated prisoners, however, greatly restrict the nature and quantity of mental health services that they can receive. In this article, we describe the use of isolation (called segregation by prison officials) to confine prisoners with serious mental illness, the psychological consequences of such confinement, and the response of U.S. courts and human rights experts. We then address the challenges and human rights responsibilities of physicians confronting this prison practice. We conclude by urging professional organizations to adopt formal positions against the prolonged isolation of prisoners with serious mental illness. PMID- 20305084 TI - Assessment of malingering with repeat forensic evaluations: patient variability and possible misclassification on the SIRS and other feigning measures. AB - Patients with Axis I disorders often fluctuate markedly in their clinical presentations in forensic and other professional settings. Although such fluctuations could suggest ineffectual efforts at malingering, more likely explanations include confusion or poor insight into psychopathology, imprecision in the assessment methods, or actual changes in symptomatology. An important concern is whether such fluctuations, common in repeat forensic evaluations, might lead to false-positive results-specifically, the misclassifications of patients as malingerers. We used the Structured Interview of Reported Symptoms (SIRS) to examine the effects of repeat administration of the interview on 52 likely genuine forensic inpatients. As expected, test-retest correlations for individual SIRS scales were highly variable. Despite this variability, the magnitude of differences remained small. The SIRS produced no errors in the classification of likely genuine forensic inpatients at the first or the repeat administrations. Implications of variable clinical presentations for other feigning measures are considered. PMID- 20305085 TI - My father's advocacy for a right to treatment. PMID- 20305086 TI - Comment on: POWs versus torturers: forensic evaluation of military personnel. PMID- 20305087 TI - A lentiviral functional proteomics approach identifies chromatin remodeling complexes important for the induction of pluripotency. AB - Protein complexes and protein-protein interactions are essential for almost all cellular processes. Here, we establish a mammalian affinity purification and lentiviral expression (MAPLE) system for characterizing the subunit compositions of protein complexes. The system is flexible (i.e. multiple N- and C-terminal tags and multiple promoters), is compatible with Gateway cloning, and incorporates a reference peptide. Its major advantage is that it permits efficient and stable delivery of affinity-tagged open reading frames into most mammalian cell types. We benchmarked MAPLE with a number of human protein complexes involved in transcription, including the RNA polymerase II-associated factor, negative elongation factor, positive transcription elongation factor b, SWI/SNF, and mixed lineage leukemia complexes. In addition, MAPLE was used to identify an interaction between the reprogramming factor Klf4 and the Swi/Snf chromatin remodeling complex in mouse embryonic stem cells. We show that the SWI/SNF catalytic subunit Smarca2/Brm is up-regulated during the process of induced pluripotency and demonstrate a role for the catalytic subunits of the SWI/SNF complex during somatic cell reprogramming. Our data suggest that the transcription factor Klf4 facilitates chromatin remodeling during reprogramming. PMID- 20305088 TI - Building macromolecular assemblies by information-driven docking: introducing the HADDOCK multibody docking server. AB - Over the last years, large scale proteomics studies have generated a wealth of information of biomolecular complexes. Adding the structural dimension to the resulting interactomes represents a major challenge that classical structural experimental methods alone will have difficulties to confront. To meet this challenge, complementary modeling techniques such as docking are thus needed. Among the current docking methods, HADDOCK (High Ambiguity-Driven DOCKing) distinguishes itself from others by the use of experimental and/or bioinformatics data to drive the modeling process and has shown a strong performance in the critical assessment of prediction of interactions (CAPRI), a blind experiment for the prediction of interactions. Although most docking programs are limited to binary complexes, HADDOCK can deal with multiple molecules (up to six), a capability that will be required to build large macromolecular assemblies. We present here a novel web interface of HADDOCK that allows the user to dock up to six biomolecules simultaneously. This interface allows the inclusion of a large variety of both experimental and/or bioinformatics data and supports several types of cyclic and dihedral symmetries in the docking of multibody assemblies. The server was tested on a benchmark of six cases, containing five symmetric homo oligomeric protein complexes and one symmetric protein-DNA complex. Our results reveal that, in the presence of either bioinformatics and/or experimental data, HADDOCK shows an excellent performance: in all cases, HADDOCK was able to generate good to high quality solutions and ranked them at the top, demonstrating its ability to model symmetric multicomponent assemblies. Docking methods can thus play an important role in adding the structural dimension to interactomes. However, although the current docking methodologies were successful for a vast range of cases, considering the variety and complexity of macromolecular assemblies, inclusion of some kind of experimental information (e.g. from mass spectrometry, nuclear magnetic resonance, cryoelectron microscopy, etc.) will remain highly desirable to obtain reliable results. PMID- 20305090 TI - Epigenetic signatures of Silver-Russell syndrome. PMID- 20305089 TI - Quantitative proteomics analysis of inborn errors of cholesterol synthesis: identification of altered metabolic pathways in DHCR7 and SC5D deficiency. AB - Smith-Lemli-Opitz syndrome (SLOS) and lathosterolosis are malformation syndromes with cognitive deficits caused by mutations of 7-dehydrocholesterol reductase (DHCR7) and lathosterol 5-desaturase (SC5D), respectively. DHCR7 encodes the last enzyme in the Kandutsch-Russel cholesterol biosynthetic pathway, and impaired DHCR7 activity leads to a deficiency of cholesterol and an accumulation of 7 dehydrocholesterol. SC5D catalyzes the synthesis of 7-dehydrocholesterol from lathosterol. Impaired SC5D activity leads to a similar deficiency of cholesterol but an accumulation of lathosterol. Although the genetic and biochemical causes underlying both syndromes are known, the pathophysiological processes leading to the developmental defects remain unclear. To study the pathophysiological mechanisms underlying SLOS and lathosterolosis neurological symptoms, we performed quantitative proteomics analysis of SLOS and lathosterolosis mouse brain tissue and identified multiple biological pathways affected in Dhcr7(Delta3 5/Delta3-5) and Sc5d(-/-) E18.5 embryos. These include alterations in mevalonate metabolism, apoptosis, glycolysis, oxidative stress, protein biosynthesis, intracellular trafficking, and cytoskeleton. Comparison of proteome alterations in both Dhcr7(Delta3-5/Delta3-5) and Sc5d(-/-) brain tissues helps elucidate whether perturbed protein expression was due to decreased cholesterol or a toxic effect of sterol precursors. Validation of the proteomics results confirmed increased expression of isoprenoid and cholesterol synthetic enzymes. This alteration of isoprenoid synthesis may underlie the altered posttranslational modification of Rab7, a small GTPase that is functionally dependent on prenylation with geranylgeranyl, that we identified and validated in this study. These data suggested that although cholesterol synthesis is impaired in both Dhcr7(Delta3-5/Delta3-5) and Sc5d(-/-) embryonic brain tissues the synthesis of nonsterol isoprenoids may be increased and thus contribute to SLOS and lathosterolosis pathology. This proteomics study has provided insight into the pathophysiological mechanisms of SLOS and lathosterolosis, and understanding these pathophysiological changes will help guide clinical therapy for SLOS and lathosterolosis. PMID- 20305091 TI - The identification of implicit theories in domestic violence perpetrators. AB - An understanding of how the beliefs of domestically violent offenders might influence their abusive behavior is central to the development and delivery of any intervention program that aims to reduce the risk of further violence against women and children. This article reports the results of a preliminary investigation into the core beliefs of a sample of domestically violent men. Three major themes emerged from an analysis of the accounts of their violence, which were understood in relation to three implicit theories that participants held about themselves, their relationships, and the world. These are discussed in terms of previous studies of offender cognition, how domestic violence programs might be conceptualized, and their implications for practice. PMID- 20305092 TI - Kidney injury molecule-1 expression in rat proximal tubule after treatment with segment-specific nephrotoxicants: a tool for early screening of potential kidney toxicity. AB - Dose-response expression of kidney injury molecule-1 (KIM-1) gene in kidney cortex and its correlation with morphology and traditional biomarkers of nephrotoxicity (plasma creatinine and blood urea nitrogen, BUN) or segment specific marker of proximal tubule injury (kidney glutamine synthetase, GSK) were studied in male rats treated with proximal tubule segment-specific nephrotoxicants. These included hexachloro-1:3-butadiene (HCBD, S(3) segment specific), potassium dichromate (chromate, S(1)-S(2) segment-specific), and cephaloridine (Cph, S(2) segment-specific). Rats were treated with a single intraperitoneal (ip) injection of HCBD 25, 50, and 100 mg/kg, subcutaneous (sc) injection of chromate 8, 12.5, and 25 mg/kg; or ip injection of Cph 250, 500, and 1,000 mg/kg. KIM-1 gene showed a dose-dependent up-regulation induced by all segment-specific nephrotoxicants. Interestingly, magnitude of the up-regulation reflected the severity of microscopic tubular changes (degeneration, necrosis, and regeneration). Even low-severity microscopic observations were evidenced by significant gene expression changes. Furthermore, KIM-1 showed significant up regulation even in the absence of morphological changes. In contrast, traditional and specific markers demonstrated low sensitivity or specificity. In conclusion, this study suggested KIM-1 as a sensitive molecular marker of different levels of tubular injury, and it is likely to represent a potential tool for early screening of nephrotoxicants. PMID- 20305093 TI - Early toxicology signal generation in the mouse. AB - The rat has been the preferred rodent toxicology species since before regulatory requirements have been in place, and there exists in the pharmaceutical industry and the regulatory agencies a significant amount of historical data for the rat. The resulting experience base with the rat makes the possibility of replacing it with the mouse for regulated toxicology studies untenable for all but the most extreme circumstances. However, toxicologists are very familiar with the mouse as a model for chronic carcinogenicity studies, and there exist multiple preclinical mouse models of disease. The authors evaluated the use of the mouse for early in vivo toxicology signal generation and prioritization of small molecule lead compounds prior to nomination of a development candidate. In five-day oral gavage studies with three test agents in the mouse, the authors were able to identify the same dose-limiting toxicities as those identified in the rat, including examples of compound-mediated hemolysis as well as microscopic lesions in the alimentary canal, kidney, and pancreas. Performing early signal generation studies in the mouse allows for earlier assessment of the safety liabilities of small molecules, requires significantly less compound, and allows evaluation of more compounds earlier in the project's life cycle. PMID- 20305094 TI - Managing chromoblastomycosis. AB - Chromoblastomycosis is a subcutaneous fungal infection caused by the traumatic inoculation of the skin with pigmented saprophytic moulds. Although infection is rarely fatal, it is characteristically chronic and can be complicated by lymphatic damage and malignant transformation. Despite a variety of treatment modalities, which are often combined and include long courses of antifungals, surgical excision and destructive physical therapies, it remains one of the most difficult deep mycotic infections to eradicate. PMID- 20305095 TI - Resurgence of yaws in Tanna, Vanuatu: time for a new approach? AB - Recent reports from the island of Tanna in Vanuatu suggest that yaws has resurged. We carried out a serological and clinical survey to determine the prevalence and clinical presentation of yaws on the island. A total of 306 random serum samples were tested for rapid plasma reagin and rapid diagnostic determine syphilis: 31.04% were positive for one or both tests; 39.8% of children surveyed in three schools had skin lesions consistent with yaws; and there were only two cases of secondary yaws osteitis and no cases of tertiary yaws. These results confirm that the disease has resurged but appears to be attenuated. Intramuscular benzathine penicillin is the currently recommended treatment for yaws. We suggest that a stat dose of oral azithromycin would be a more accessible treatment as it could be prescribed by village health workers and therefore enable yaws control to be more easily incorporated into other primary health-care programmes. PMID- 20305096 TI - Rising mother-to-child HIV transmission in a resource-limited breastfeeding population. AB - The objective of this study was to determine mother to child HIV transmission rates at different time points in a breastfeeding cohort enrolled in a single dose nevirapine program in Harare, Zimbabwe. Between 2002-2004, 434 HIV-positive mothers and their infants were recruited and followed up from delivery to 15 months. Infant blood specimens were collected for HIV testing at these time points. The majority of the patients (78%) received single dose nevirapine. The overall HIV transmission rate was 21.8% (17.8-25.8). Receiving single dose nevirapine was protective against HIV vertical transmission although statistically insignificant (relative risk: 0.76; 95% CI: 0.49-1.19). Breastfeeding was not found to be associated with HIV vertical transmission (P = 0.612). In this resource-limited setting, HIV transmission rates are high. Efforts to use more efficacious regimens to arrest HIV vertical transmission are required. PMID- 20305097 TI - Surgery in Malawi--the training of clinical officers. AB - Doctors are scarce in Malawi and, therefore, a considerable amount of work is carried out by paramedical clinical officers (COs). Although their training is limited, they take care of the majority of patients in the country. The CO project started in the Southern region of Malawi in 2005 in order to improve the number of surgical and gynaecological operations and skills of COs. Nine district hospitals and eight Christian Health Organisation of Malawi (CHAM) hospitals were visited and all surgical registers from 2004 and 2007 were analysed and COs were interviewed. The interviewed COs felt at ease when performing operations; in 2004 they performed 61% and in 2007 87% of the surgical and gynaecological procedures itemised in the questionnaire. In 2004 a total of 18,524 operations were registered in the 17 hospitals in the Southern region of Malawi and there were 19,644 in 2007. Certified COs performed significantly more surgical than gynaecological operations. In 2004, 8.4% of their performed operations consisted of major surgical operations and 17.7% in 2007. A two-year postgraduate training in surgery is being developed for them but, in the meantime, it will be necessary to ensure a continuation of the CO project in the central and northern regions of Malawi. PMID- 20305098 TI - Comparing vaginal and sublingual administration of misoprostol for labour induction in women with intra-uterine fetal death. AB - The objective of this study was to compare complications and effectiveness of induction after vaginal and sublingual administration of misoprostol for labor induction in women with intra-uterine fetal death (IUFD). In a district hospital in Ghana, 23 women with IUFD who underwent labor induction with sublingual misoprostol were compared with a control group of 21 women who received vaginal misoprostol. In the vaginal group 28.6% had one or more complications compared to 21.7% in the sublingual group. In the sublingual group three inductions did not lead to delivery within 48 hours (13%), compared to four in the other group (19%). The mean induction-to-delivery time in the sublingual group was 13 hours and 17 hours in the vaginal group. In this study, both sublingual and vaginal misoprostol were safe and efficient for labor induction in women with IUFD. However, more research on larger numbers of patients is needed, in order to compare complications. PMID- 20305099 TI - Postmortem findings in HIV/AIDS patients in a tertiary care hospital in rural South Africa. AB - South Africa has the largest number of people living with HIV/AIDS, and various associated infectious and noninfectious conditions contribute towards mortality. The objective of this study was to determine the important post-mortem findings in HIV-infected individuals in a high HIV burden rural area in South Africa. The patient population included HIV patients who died at the tertiary care hospital, from 2000-2008. Autopsies were performed according to standard protocols and diagnoses were made with additional laboratory investigations wherever required. A total of 86 patients were autopsied (30 males, 56 females). The major postmortem findings were related to infections, with 38% of the patients having had some form of tuberculosis, followed by pyogenic infections--pneumonias (21.5%), meningitis (10.1%) and septicemias (5.1%). Other important infections included opportunistic fungi like cryptococcosis (7.6%) and pneumocystis pneumonia (8.9%). Among the noninfectious conditions, the findings seen were predominantly related to liver (10.1%) and cardiac involvement (10.1%). PMID- 20305100 TI - Clinical profile of women with severe anaemia in the third trimester of pregnancy. AB - Anaemia, the most common medical disorder associated with pregnancy, is a silent killer. Most severely anaemic pregnant women are asymptomatic and present late in the third trimester with medical and obstetric complications. PMID- 20305101 TI - Rhabdomyolysis in falciparum malaria--a series of twelve cases (five children and seven adults). AB - There are very few reports in the literature of rhabdomyolysis in falciparum malaria and they mostly consist of single case studies. A report from Sri Lanka described a single patient with myoglobinuria and skeletal muscle necrosis. Taylor and Prosser reported a single case of rhabdomyolysis with renal failure. We report on 12 patients with evidence of skeletal muscle injury in severe malaria from Rourkela, Orissa State, India. PMID- 20305102 TI - Bacterial aetiology and antimicrobial resistance of community-acquired pneumonia in the elderly and younger adults. AB - This study was undertaken in order to compare the frequency of bacterial agents of community-acquired pneumonia (CAP) and their antimicrobial resistance in the elderly and younger adults admitted to a teaching hospital in Hamedan, Iran. A total of 150 cases of CAP, including 81 elderly and 69 younger adults, were evaluated. The most frequently identified pathogens in younger adults were Moraxella catarralis (11.5%), Streptococcus pneumonia (10.1%) and Staphylococcus aureus (10.1%); while in the elderly the most frequent were S. pneumonia (12.3%), S. aureus (6.1%) and Pseudomonas aeruginosa (6.1%). No significant differences were observed between the frequency and antimicrobial resistance pattern of isolated pathogens in either age group. We concluded that the cause of CAP in the elderly follows the general trend of infection in the younger population. Increased resistance of isolated bacteria to the current antibiotics highlights the need for further investigation of newer antibiotics for the treatment of CAP. PMID- 20305103 TI - Leptospirosis in suspected cases of dengue in Jamaica, 2002-2007. AB - Due to overlapping clinical features with other febrile illnesses, the diagnosis of leptospirosis is often overlooked, resulting in delay in treatment and increased mortality. In this study the prevalence of leptospirosis was determined in 590 patients with dengue-like illnesses using the Leptospira IgM dipstick and dengue enzyme-linked immunosorbent assays. Leptospira IgM antibodies were found in 27 (5.0%) patients. Dengue IgM negative (6.9% versus 2.5%, P < 0.05) and dengue IgG positive patients (8.0% versus 3.5%, P < 0.01) were more likely to be leptospira IgM positive. Fever, skin rash, central nervous system and respiratory involvement were the most common presenting features. The presence of arthralgia (P = 0.016), hepatitis (P = 0.000), jaundice (P = 0.003), splenomegaly (P = 0.041) and haematuria (P = 0.029) were associated with leptospirosis. In countries with an endemicity of leptospirosis and dengue it is important that patients with dengue-like illnesses, especially those with no serological evidence of current primary dengue infection, be investigated for leptospirosis. PMID- 20305104 TI - Outbreak of beriberi in the state of Maranhao, Brazil: revisiting the mycotoxin aetiologic hypothesis. AB - Beriberi is caused by thiamine deficiency. Early 20th century epidemics in Japan were attributed to rice contaminated by citreoviridin mycotoxin. Our investigation of an outbreak of beriberi in Brazil showed an association of beriberi with the consumption of poor quality subsistence farming rice, although, unlike other investigators of this outbreak, we did not identify citreoviridin producing fungi in the implicated rice. PMID- 20305105 TI - Hospital-based injury data in Malawi: strategies for data collection and feasibility of trauma scoring tools. AB - Injury is a major cause of morbidity and mortality in developing countries. Utilizing a partnership between Kamuzu Central Hospital (KCH) and the University of North Carolina Departments of Surgery, we describe an approach to injury surveillance, examine the utility of trauma scoring systems, and outline steps necessary before such scoring systems can be reliably instituted in a resource constrained setting. PMID- 20305106 TI - Hair dye poisoning--an emerging problem in the tropics: an experience from a tertiary care hospital in South India. AB - Super-Vasmol, a cheap, freely-available hair dye is emerging as a major cause of suicidal poisoning in India. It contains potential toxins including paraphenylene diamine, resorcinol, sodium ethylenediaminetetraacetic acid and propylene glycol which can result in multiorgan dysfunction. A retrospective study was conducted over 3.5 years (January 2006-July 2009) of 13 consecutive patients with Super Vasmol poisoning admitted to a tertiary care, referral hospital in South India. A chart review including records of clinical presentations, laboratory findings and treatment details was carried out. Eleven of the patients were women and the mean age was 27.2 years. The predominant clinical features were cervico-facial oedema and pain, cola-coloured urine and oliguria. Laboratory investigations revealed elevated hepatic transaminases (100%), leucocytosis (92.3%), elevated creatinine phosphokinase (92.3%), metabolic acidosis (84.6%), hypocalcaemia (61.5%), hyperphosphataemia (46.2%) and renal failure (38.5%). Eight of the patients were discharged with complete recovery. Trends towards a poor outcome were evident among the following patients: late presentation at our centre; when no gastric lavage was done at the primary-care centre; those requiring tracheostomy/intubation at the primary centre; presentation with a low Glasgow Coma Score or seizures; established renal failure; and those who subsequently require dialysis, mechanical ventilation or intensive care. Hair dye poisoning classically presents with cervico-facial oedema, severe rhabdomyolysis and renal failure. Early therapy with tracheostomy and aggressive forced diuresis are essential in order to prevent the high mortality associated with this toxin. It is imperative to raise public awareness of the potential toxicity of the dye as well as to educate physicians about the need for aggressive and early treatment. PMID- 20305107 TI - Percutaneous continuous ambulatory peritoneal dialysis (CAPD) catheter insertion- a preferred option for developing countries. AB - Continuous ambulatory peritoneal dialysis (CAPD) as a modality of renal replacement therapy in patients with chronic kidney disease stage 5 (CKD 5) has the advantage of being a home-based therapy and is a preferred option in patients with inadequate access to haemodialysis and transplantation facilities and in those infected with HIV and other blood-borne viruses. While open surgical CAPD catheter placement has been the conventional mainstay of access placement, percutaneous techniques are being increasingly used with similar success rates. We report our experience over the past two years with blind insertion of the swan neck percutaneous double-cuffed Tenckhoff CAPD catheter using a trocar. There was considerable decrease in hospital stay and surgical costs. There was only one major complication of injury to the jejunal mesenteric artery requiring emergency laparotomy in one patient. In three patients, drain of peritoneal fluid was inadequate, presumably due to omental wrapping around the in-dwelling catheter, and required surgical removal of the omentum. PMID- 20305108 TI - Can urine dipstick tests detect renal impairment in Plasmodium falciparum malaria in a rural setup? AB - Renal impairment in falciparum malaria leads to poor prognosis. Serum creatinine is the mainstay of diagnosis. However, the serum creatinine concentration is only observed when the glomerular filtration rate falls below 50%. We evaluated the use of the urine dipstick method to predict renal impairment in 77 patients. Twenty-three (29.8%) had haematuria and 52 (67.5%) had urinary protein > or = 300 mg/L. Renal impairment (plasma creatinine > or = 1.2 mg/dL) was observed in 17 patients. The sensitivity and specificity of haematuria in the detection of renal impairment was 94.1% and 90.8%, but for proteinuria it was 88.2% and 62.7%, respectively. There was a positive correlation of plasma urea and creatinine with haematuria (r = 0.56, P < 0.001; r = 0.46, P < 0.01) but not with proteinuria. The detection of haematuria using a dipstick seems to be a highly specific and sensitive method of observing renal impairment in malaria. This is probably the first study which utilizes a commonly available tool that can be easily adopted for early recognition in rural areas. PMID- 20305109 TI - MRSA--too many hurdles to overcome: a study from Central India. AB - Methicillin-resistant Staphylococcus aureus (MRSA) are commonly associated with nosocomial infections and are usually resistant to many antibiotics. This study describes the prevalence of MRSA strains and their antibiogram in a tertiary care hospital in Central India. The detection of MRSA was done by a cefoxitin (30 microg) disc diffusion test. Antibiotic sensitivity tests were done as per the Clinical and Laboratory Standards Institute guidelines 2006. Of the 280 S. aureus strains studied: 145 (51.8%) strains were MRSA; 51 (35.2%) MRSA strains were inducible clindamycin resistant; and all (100%) MRSA strains were resistant to penicillin and sensitive to vancomycin and linezolid. In order to detect the MRSA strains, cefoxitin disc diffusion tests should be used routinely in any microbiology laboratory to enable prompt treatment for the patient. PMID- 20305110 TI - Epidemiology of needlestick injuries among health-care workers in Awassa City, Southern Ethiopia. AB - Accidental needlestick injuries sustained by health-care workers are a common occupational hazard and a public health issue in health-care settings. An analytical cross-sectional study was conducted and 30.9% of health-care workers had experienced at least one needlestick injury in the previous year. PMID- 20305111 TI - Amputation and disability following snakebite in Nigeria. AB - Snakebite is an important cause of amputation and disability in rural communities throughout the tropics. However, the details of the causes, types and estimates of disability are lacking. This report describes 16 snakebite victims who had amputations, including two who had above-knee amputations. The patients presented with limb swelling (16), gangrene (15), ischaemia (4) and three had possible compartment syndrome. All the patients used ineffective time wasting remedies that were potentially harmful as first-aid. The median delay to hospital following bite was 2.5 days. In order to prevent disability, efforts should be made to: reduce delay before hospital presentation; improve the knowledge of first-aid; provide effective antivenoms; improve wound and clinical care in communities; and improve facilities. PMID- 20305112 TI - Bilateral blindness following snakebite. AB - Snakebite is an important cause of morbidity and mortality in Nigeria, as in many parts of the tropics. However, blindness is a rare complication. Reported cases have usually followed bites by neurotoxic snakes such as the cobra. Reports of blindness produced by the bite of haematotoxic snakes are extremely rare. We report the case of bilateral blindness following a bite from a carpet viper. The literature on the subject matter is reviewed and the possible mechanisms of snakebite-induced blindness are discussed. PMID- 20305113 TI - Managing scorpion stings in the tropics: chloroquine as an effective drug. AB - We report on a fairly familiar alternative use of injection chloroquine in district hospitals in Ghana. Within a period of three years, pain control among six patients with scorpion sting was achieved successfully on an outpatient department basis with injection chloroquine at the Holy Family Hospital, Techiman, Ghana. PMID- 20305114 TI - Hepatic pregnancy managed conservatively. AB - We present a case of hepatic pregnancy and discuss expectant management, use of newer imaging techniques and approaches to management, such as leaving the placenta in situ, the use of magnetic resonance imaging and sonography in the follow-up of placental involution. This case report illustrates that conservative management is feasible. PMID- 20305115 TI - Erythema nodosum in the course of Crimean-Congo haemorrhagic fever. AB - Crimean-Congo haemorrhagic fever is an emerging zoonosis with a wide geographic distribution and protean clinical manifestations. The main pathogenesis of this infection has not been elucidated. Erythema nodosum is an immunologically mediated dermatologic disease and the most common form of panniculitis that has been associated with many infections and inflammatory disorders. We describe a case of Crimean-Congo haemorrhagic fever with severe bleeding diathesis and hepatic failure that was successfully treated with oral ribavirin. The patient presented with erythema nodosum in the course of disease. Crimean-Congo haemorrhagic fever and erythema nodosum have not been reported to occur together. We present the first reported case of erythema nodosum associated with this emerging viral infection. Furthermore, it may influence our opinion about pathogenesis and immunologic mechanisms of this disease. PMID- 20305116 TI - Tuberculosis of uterine cervix: a report of two cases with variable clinical presentation. AB - Tuberculosis (TB) of the cervix is a rare disease. We describe two cases of tuberculous cervicitis with variable clinical presentation. In one case, a young woman presented with primary infertility and secondary amenorrhoea. The other is a perimenopausal woman with irregular vaginal bleeding and postcoital blood stained discharge. The diagnosis was confirmed on histopathological examination of the endocervical curettings and a cervical biopsy. The patients were given six months of anti-tuberculous therapy and responded well. PMID- 20305117 TI - Mucormycosis. AB - Mucormycosis is an aggressive, opportunistic infection caused by fungi belonging to the class of Phycomycetes. Rhino-oculo-cerebral mucormycosis is the commonest anatomical presentation of mucormycosis and is a potentially fatal disease. We report here a case of a 65-year-old diabetic female who presented with a locally invasive type of mucormycosis and was treated successfully by surgical debridement along with medical treatment (Amphoterecin-B and insulin). PMID- 20305118 TI - Apomixis and gene expression in Boechera. PMID- 20305119 TI - Different words, same message: how grasses and Arabidopsis say "hold the bract". PMID- 20305120 TI - Carbon starved anther encodes a MYB domain protein that regulates sugar partitioning required for rice pollen development. AB - In flowering plants, sink tissues rely on transport of carbohydrates from photosynthetic tissues (sources) for nutrition and energy. However, how sugar partitioning in plants is regulated at the molecular level during development remains unknown. We have isolated and characterized a rice (Oryza sativa) mutant, carbon starved anther (csa), that showed increased sugar contents in leaves and stems and reduced levels of sugars and starch in floral organs. In particular, the csa mutant had reduced levels of carbohydrates in later anthers and was male sterile. The csa mutant had reduced accumulation of (14)C-labeled sugars in anther sink tissue. CSA was isolated by map-based cloning and was shown to encode an R2R3 MYB transcription factor that was expressed preferentially in the anther tapetal cells and in the sugar-transporting vascular tissues. In addition, the expression of MST8, encoding a monosaccharide transporter, was greatly reduced in csa anthers. Furthermore, CSA was found to be associated in vivo and in vitro with the promoter of MST8. Our findings suggest that CSA is a key transcriptional regulator for sugar partitioning in rice during male reproductive development. This study also establishes a molecular model system for further elucidation of the genetic control of carbon partitioning in plants. PMID- 20305121 TI - A conserved mechanism of bract suppression in the grass family. AB - Suppression of inflorescence leaf, or bract, growth has evolved multiple times in diverse angiosperm lineages, including the Poaceae and Brassicaceae. Studies of Arabidopsis thaliana mutants have revealed several genes involved in bract suppression, but it is not known if these genes play a similar role in other plants with suppressed bracts. We identified maize (Zea mays) tassel sheath (tsh) mutants, characterized by the loss of bract suppression, that comprise five loci (tsh1-tsh5). We used map-based cloning to identify Tsh1 and found that it encodes a GATA zinc-finger protein, a close homolog of HANABA TARANU (HAN) of Arabidopsis. The bract suppression function of Tsh1 is conserved throughout the grass family, as we demonstrate that the rice (Oryza sativa) NECK LEAF1 (NL1) and barley (Hordeum vulgare) THIRD OUTER GLUME (TRD) genes are orthologous with Tsh1. Interestingly, NL1/Tsh1/TRD expression and function are not conserved with HAN. The existence of paralogous NL1/Tsh1/TRD-like genes in the grasses indicates that the NL1/Tsh1/TRD lineage was created by recent duplications that may have facilitated its neofunctionalization. A comparison with the Arabidopsis genes regulating bract suppression further supports the hypothesis that the convergent evolution of bract suppression in the Poaceae involved recruitment of a distinct genetic pathway. PMID- 20305122 TI - Apomictic and sexual ovules of Boechera display heterochronic global gene expression patterns. AB - We have compared the transcriptomic profiles of microdissected live ovules at four developmental stages between a diploid sexual and diploid apomictic Boechera. We sequenced >2 million SuperSAGE tags and identified (1) heterochronic tags (n = 595) that demonstrated significantly different patterns of expression between sexual and apomictic ovules across all developmental stages, (2) stage specific tags (n = 577) that were found in a single developmental stage and differentially expressed between the sexual and apomictic ovules, and (3) sex specific (n = 237) and apomixis-specific (n = 1106) tags that were found in all four developmental stages but in only one reproductive mode. Most heterochronic and stage-specific tags were significantly downregulated during early apomictic ovule development, and 110 were associated with reproduction. By contrast, most late stage-specific tags were upregulated in the apomictic ovules, likely the result of increased gene copy number in apomictic (hexaploid) versus sexual (triploid) endosperm or of parthenogenesis. Finally, we show that apomixis specific gene expression is characterized by a significant overrepresentation of transcription factor activity. We hypothesize that apomeiosis is associated with global downregulation at the megaspore mother cell stage. As the diploid apomict analyzed here is an ancient hybrid, these data are consistent with the postulated link between hybridization and asexuality and provide a hypothesis for multiple evolutionary origins of apomixis in the genus Boechera. PMID- 20305123 TI - Promoters of the barley germin-like GER4 gene cluster enable strong transgene expression in response to pathogen attack. AB - Immunity of plants triggered by pathogen-associated molecular patterns (PAMPs) is based on the execution of an evolutionarily conserved defense response that includes the accumulation of pathogenesis-related (PR) proteins as well as multiple other defenses. The most abundant PR transcript of barley (Hordeum vulgare) leaf epidermis attacked by the powdery mildew fungus Blumeria graminis f. sp hordei encodes the germin-like protein GER4, which has superoxide dismutase activity and functions in PAMP-triggered immunity. Here, we show that barley GER4 is encoded by a dense cluster of tandemly duplicated genes (GER4a-h) that underwent several cycles of duplication. The genomic organization of the GER4 locus also provides evidence for repeated gene birth and death cycles. The GER4 promoters contain multiple WRKY factor binding sites (W-boxes) preferentially located in promoter fragments that were exchanged between subfamily members by gene conversion. Mutational analysis of TATA-box proximal W-boxes used GER4c promoter-beta-glucuronidase fusions to reveal their enhancing effects and functional redundancy on pathogen-induced promoter activity. The data suggest enhanced transcript dosage as an evolutionary driving force for the local expansion and functional redundancy of the GER4 locus. In addition, the GER4c promoter provides a tool to study signal transduction of PAMP-triggered immunity and to engineer strictly localized and pathogen-regulated disease resistance in transgenic cereal crops. PMID- 20305124 TI - The Arabidopsis floral homeotic proteins APETALA3 and PISTILLATA negatively regulate the BANQUO genes implicated in light signaling. AB - The Arabidopsis thaliana MADS box transcription factors APETALA3 (AP3) and PISTILLATA (PI) heterodimerize and are required to specify petal identity, yet many details of how this regulatory process is effected are unclear. We have identified three related genes, BHLH136/BANQUO1 (BNQ1), BHLH134/BANQUO2 (BNQ2), and BHLH161/BANQUO3 (BNQ3), as being directly and negatively regulated by AP3 and PI in petals. BNQ1, BNQ2, and BNQ3 encode products belonging to a family of atypical non-DNA binding basic helix-loop-helix (bHLH) proteins that heterodimerize with and negatively regulate bHLH transcription factors. We show that bnq3 mutants have pale-green sepals and carpels and decreased chlorophyll levels, suggesting that BNQ3 has a role in regulating light responses. The ap3 bnq3 double mutant displays pale second-whorl organs, supporting the hypothesis that BNQ3 is downstream of AP3. Consistent with a role in light response, we show that the BNQ gene products regulate the function of HFR1 (for LONG HYPOCOTYL IN FAR-RED1), which encodes a bHLH protein that regulates photomorphogenesis through modulating phytochrome and cryptochrome signaling. The BNQ genes also are required for appropriate regulation of flowering time. Our results suggest that petal identity is specified in part through downregulation of BNQ-dependent photomorphogenic and developmental signaling pathways. PMID- 20305125 TI - Transient basal ganglia and thalamic involvement following Mycoplasma pneumoniae infection associated with antiganglioside antibodies. AB - A case of acute and reversible bilateral basal ganglia with thalami involvement associated with serological evidence of Mycoplasma pneumoniae infection is reported. Increased titers of immunoglobulin M antibodies against GM1 ganglioside components were found during an acute phase of neurological illness. Brain magnetic resonance imaging (MRI) showed bilateral involvement of the basal ganglia and thalamus, which disappeared 1 month later. The child recovered fully after corticosteroid and immunoglobulin therapy, and antiganglioside antibodies returned to within the normal range. The authors speculate on the diagnostic hypothesis regarding selective basal ganglia and thalamic involvement and the relationship with anti-GM1 ganglioside immunoglobulin M antibodies. PMID- 20305126 TI - Identification of glycine N-acyltransferase-like 2 (GLYATL2) as a transferase that produces N-acyl glycines in humans. AB - The discovery of glycine conjugates of long-chain fatty acids (N-acyl glycines) in the brain and other non-neuronal tissues has led to the identification of an emerging class of bioactive lipids. The biological activities of N-acyl glycines include antinociceptive, anti-inflammatory and antiproliferative effects, and activation of G-protein-coupled receptors. However, despite the fact that N-acyl glycines are emerging as a distinct lipid signaling family, pathways for their production are not fully elucidated. Here we report on the characterization of human glycine N-acyltransferase-like 2 (hGLYATL2), a member of a gene family of 4 putative glycine conjugating enzymes, and show that it synthesizes various N-acyl glycines. Recombinantly expressed hGLYATL2 efficiently conjugated oleoyl-CoA, arachidonoyl-CoA, and other medium- and long-chain acyl-CoAs to glycine. The enzyme was specific for glycine as an acceptor molecule, and preferentially produced N-oleoyl glycine. The hGLYATL2 enzyme is localized to the endoplasmic reticulum, and the mRNA shows highest expression in salivary gland and trachea, but is also detected in spinal cord and skin fibroblasts. The expression pattern and the identification of high levels of N-acyl glycines in skin and lung may indicate a role for N-acyl glycines in barrier function/immune response and the potential role of hGLYATL2 in this regard is discussed. PMID- 20305127 TI - Regulation of homocysteine metabolism and methylation in human and mouse tissues. AB - Hyperhomocysteinemia is an independent risk factor for cardiovascular disease. Homocysteine (Hcy) metabolism involves multiple enzymes; however, tissue Hcy metabolism and its relevance to methylation remain unknown. Here, we established gene expression profiles of 8 Hcy metabolic and 12 methylation enzymes in 20 human and 19 mouse tissues through bioinformatic analysis using expression sequence tag clone counts in tissue cDNA libraries. We analyzed correlations between gene expression, Hcy, S-adenosylhomocysteine (SAH), and S adenosylmethionine (SAM) levels, and SAM/SAH ratios in mouse tissues. Hcy metabolic and methylation enzymes were classified into two types. The expression of Type 1 enzymes positively correlated with tissue Hcy and SAH levels. These include cystathionine beta-synthase, cystathionine-gamma-lyase, paraxonase 1, 5,10-methylenetetrahydrofolate reductase, betaine:homocysteine methyltransferase, methionine adenosyltransferase, phosphatidylethanolamine N-methyltransferases and glycine N-methyltransferase. Type 2 enzyme expressions correlate with neither tissue Hcy nor SAH levels. These include SAH hydrolase, methionyl-tRNA synthase, 5-methyltetrahydrofolate:Hcy methyltransferase, S-adenosylmethionine decarboxylase, DNA methyltransferase 1/3a, isoprenylcysteine carboxyl methyltransferases, and histone-lysine N-methyltransferase. SAH is the only Hcy metabolite significantly correlated with Hcy levels and methylation enzyme expression. We established equations expressing combined effects of methylation enzymes on tissue SAH, SAM, and SAM/SAH ratios. Our study is the first to provide panoramic tissue gene expression profiles and mathematical models of tissue methylation regulation. PMID- 20305128 TI - Effects of the dietary approaches to stop hypertension diet, exercise, and caloric restriction on neurocognition in overweight adults with high blood pressure. AB - High blood pressure increases the risks of stroke, dementia, and neurocognitive dysfunction. Although aerobic exercise and dietary modifications have been shown to reduce blood pressure, no randomized trials have examined the effects of aerobic exercise combined with dietary modification on neurocognitive functioning in individuals with high blood pressure (ie, prehypertension and stage 1 hypertension). As part of a larger investigation, 124 participants with elevated blood pressure (systolic blood pressure 130 to 159 mm Hg or diastolic blood pressure 85 to 99 mm Hg) who were sedentary and overweight or obese (body mass index: 25 to 40 kg/m(2)) were randomized to the Dietary Approaches to Stop Hypertension (DASH) diet alone, DASH combined with a behavioral weight management program including exercise and caloric restriction, or a usual diet control group. Participants completed a battery of neurocognitive tests of executive function-memory-learning and psychomotor speed at baseline and again after the 4 month intervention. Participants on the DASH diet combined with a behavioral weight management program exhibited greater improvements in executive function memory-learning (Cohen's D=0.562; P=0.008) and psychomotor speed (Cohen's D=0.480; P=0.023), and DASH diet alone participants exhibited better psychomotor speed (Cohen's D=0.440; P=0.036) compared with the usual diet control. Neurocognitive improvements appeared to be mediated by increased aerobic fitness and weight loss. Also, participants with greater intima-medial thickness and higher systolic blood pressure showed greater improvements in executive function memory-learning in the group on the DASH diet combined with a behavioral weight management program. In conclusion, combining aerobic exercise with the DASH diet and caloric restriction improves neurocognitive function among sedentary and overweight/obese individuals with prehypertension and hypertension. PMID- 20305129 TI - A case-control study of levothyroxine and the risk of colorectal cancer. AB - Levothyroxine is a synthetic T(4) hormone commonly used to treat thyroid disease. Increased incidence of mostly autoimmune thyroid disease has been associated with breast and other malignancies, and thyroid hormone levels might also be associated with risk of colorectal cancer (CRC). In this population-based matched case-control study (2566 pairs) of CRC in northern Israel, use of levothyroxine for at least 5 years was assessed using structured interviews and validated by prescription records. The analysis included use of statins, aspirin, and hormone replacement therapy; CRC family history; physical activity; vegetable consumption; ethnicity; age; and sex. All statistical tests were two-sided. The use of levothyroxine was associated with a statistically significantly reduced relative risk of CRC (odds ratio = 0.59, 95% confidence interval = 0.43 to 0.82, P = .001). This association remained statistically significant after adjustment for age, sex, use of aspirin and statins, sports activity, family history of CRC, ethnic group, and level of vegetable consumption (odds ratio = 0.60, 95% confidence interval = 0.44 to 0.81, P = .001). No statistically significant interactions were seen between use of levothyroxine and aspirin, statins, or hormone replacement therapy. PMID- 20305130 TI - Contralateral second breast cancers: prediction and prevention. PMID- 20305131 TI - Re: Biomarkers predicting clinical outcome of epidermal growth factor receptor targeted therapy in metastatic colorectal cancer. PMID- 20305133 TI - Urinary incontinence and quality of life among older community-dwelling Australian men: the CHAMP study. AB - OBJECTIVE: to describe the prevalence and impact on quality of life of urinary incontinence in a population-based cohort of older community-dwelling Australian men. SUBJECTS: the population comprised 1,705 men aged >or=70 years participating in the Concord Health and Ageing in Men Project, a population-based study of urban older Australian men. METHODS: data were collected between January 2005 and June 2007, and the participation rate was 47%. Data on demographics, medical history and from the 12-item Short Form Health Survey (SF-12) and International Consultation on Incontinence Questionnaire were collected. Urinary incontinence was defined as urinary leakage at least two times a week over the past 4 weeks. RESULTS: the prevalence of urinary incontinence was 14.8%, increasing from 12.0% for men aged 70-74 years old to 16.3% for those aged >or=90 years, with urgency incontinence being the most frequent type of urinary incontinence. Daily urine leakage was reported by 3% of men. Men with incontinence had lower overall SF-12 scores with greater impact on the physical (PCS) than the mental (MCS) components of that scale. After adjusting for age, number of co-morbidities, enlarged prostate and prostate cancer, men with incontinence had worse PCS (43.6 vs 45.9) and MCS scores (52.2 vs 54.6) compared with continent men. CONCLUSION: urinary incontinence is common among older community-dwelling men and is associated with worse quality of life with greater impact on physical than mental factors. As the population ages, urinary incontinence prevalence will increase and increased resources will be needed to address this growing problem. PMID- 20305134 TI - Re: Use of isoniazid chemoprophylaxis in renal transplantation. PMID- 20305132 TI - Radiation exposure, the ATM Gene, and contralateral breast cancer in the women's environmental cancer and radiation epidemiology study. AB - BACKGROUND: Ionizing radiation is a known mutagen and an established breast carcinogen. The ATM gene is a key regulator of cellular responses to the DNA damage induced by ionizing radiation. We investigated whether genetic variants in ATM play a clinically significant role in radiation-induced contralateral breast cancer in women. METHODS: The Women's Environmental, Cancer, and Radiation Epidemiology Study is an international population-based case-control study nested within a cohort of 52,536 survivors of unilateral breast cancer diagnosed between 1985 and 2000. The 708 case subjects were women with contralateral breast cancer, and the 1397 control subjects were women with unilateral breast cancer matched to the case subjects on age, follow-up time, registry reporting region, and race and/or ethnicity. All women were interviewed and underwent full mutation screening of the entire ATM gene. Complete medical treatment history information was collected, and for all women who received radiotherapy, the radiation dose to the contralateral breast was reconstructed using radiotherapy records and radiation measurements. Rate ratios (RRs) and corresponding 95% confidence intervals (CIs) were estimated by using multivariable conditional logistic regression. All P values are two-sided. RESULTS: Among women who carried a rare ATM missense variant (ie, one carried by <1% of the study participants) that was predicted to be deleterious, those who were exposed to radiation (mean radiation exposure = 1.2 Gy, SD = 0.7) had a statistically significantly higher risk of contralateral breast cancer compared with unexposed women who carried the wild type genotype (0.01-0.99 Gy: RR = 2.8, 95% CI = 1.2 to 6.5; > or =1.0 Gy: RR = 3.3, 95% CI = 1.4 to 8.0) or compared with unexposed women who carried the same predicted deleterious missense variant (0.01-0.99 Gy: RR = 5.3, 95% CI = 1.6 to 17.3; > or =1.0 Gy: RR = 5.8, 95% CI = 1.8 to 19.0; P(trend) = .044). CONCLUSIONS: Women who carry rare deleterious ATM missense variants and who are treated with radiation may have an elevated risk of developing contralateral breast cancer. However, the rarity of these deleterious missense variants in human populations implies that ATM mutations could account for only a small portion of second primary breast cancers. PMID- 20305135 TI - Microemboli, developed during haemodialysis, pass the lung barrier and may cause ischaemic lesions in organs such as the brain. AB - BACKGROUND: Chronic haemodialysis (HD) may relieve some medical problems of terminal uraemia, but the life expectancy of patients is still significantly shortened, and there is a greatly increased morbidity. This includes pulmonary morbidity and chronic central nervous system (CNS) abnormalities. Previous studies have shown that a considerable amount of air microbubbles emanate within the blood lines of the dialysis device and pass the air detector without sounding an alarm. The aim of this study was to investigate whether microemboli can pass to the patient and whether they could be detected in the carotid artery. METHODS: A total of 54 patients on chronic HD (16 with central dialysis catheter) were investigated with an ultrasound detector (Hatteland, Royken, Norway) for the presence of microemboli at the arteriovenous (AV) fistula/graft and at the common carotid artery before and during HD. Measurements were taken for 2 and 5 min, respectively. Non-parametric paired statistics were used (Wilcoxon). RESULTS: The median number (range) and mean +/- SD of microembolic signals detected at the AV access site before commencing dialysis and during HD were 0 (0-3) and 0.2+/- 0.5 versus 4 (0-85) and 13.5 +/- 20 (P = 0.000); at the carotid artery, 1 (0-14) and 1.7 +/- 2.9 versus 2 (0-36) and 3.5 +/- 5.8 (P = 0.008). CONCLUSIONS: The infused and returning fluid from HD devices contains air microbubbles that enter the patient without triggering any alarms. These small emboli pass the lung and may cause ischaemic lesions in organs supported by the arterial circuit, such as the brain. PMID- 20305136 TI - Myocardial infarction is a complication of factor H-associated atypical HUS. AB - Cardiac complications are frequently seen in thrombotic thrombocytopaenic purpura related to ADAMTS13 deficiency. We describe the case of a 43-year-old woman who was diagnosed with an atypical haemolytic-uraemic syndrome (aHUS) associated with a pathogenic mutation in the factor H gene (C623S). After 15 days of treatment, she suffered a sudden cardiac arrest and died despite intensive resuscitation attempts. She showed only one cardiovascular risk factor, hypercholesterolaemia. Her sudden death was secondary to cardiac infarction related to a coronary thrombotic microangiopathy. This is the first case of aHUS related to a mutation in the factor H gene associated with cardiac microangiopathy. This case emphasizes the need to screen for cardiac complication during the treatment of aHUS. PMID- 20305137 TI - Genome-wide screening for risk loci of idiopathic recurrent miscarriage in a Han Chinese population: a pilot study. AB - The etiology of recurrent miscarriage (RM) is extremely heterogeneous, including genetic, immunologic, anatomic, endocrinological, and infectious anomalies. About 50% of RM is unexplained or poorly understood, which is called idiopathic recurrent miscarriage (IRM). The primary aim of this study was to identify the genetic loci that might be susceptible to IRM. Forty-four Han Chinese patients with IRM during the first trimester of their pregnancies and 44 healthy sex- and ethnic-matched controls were enrolled in this study. A case-control and genome wide study was performed and 430 polymorphic microsatellite markers were analyzed. Three loci, 6q27 (D6S446, P = .028), 9q33.1 (D9S1776, P = .037), and Xp22.11 (DXS1226, P = .008), significantly associated with IRM were found. This work identified 3 genetic regions that might harbor genes predisposed to IRM and provided new insights for future genetic and etiological study of IRM. Further study is required to confirm it. PMID- 20305138 TI - Reduced survival of type 2B von Willebrand factor, irrespective of large multimer representation or thrombocytopenia. AB - BACKGROUND: Type 2B von Willebrand factor (VWF) is characterized by gain of function mutations in the A1 domain inducing a greater affinity for platelet GPIb, possibly associated with the disappearance of large VWF multimers and thrombocytopenia. DESIGN AND METHODS: VWF survival was explored using 1-desamino 8-D-arginine vasopressin (DDAVP) in 18 patients with type 2B von Willebrand disease (VWD) and compared with their platelet count and large VWF multimer representation. RESULTS: A similarly significant shorter VWF survival, expressed as T(1/2)elimination (T(1/2)el), was observed in patients lacking large VWF multimers (type 2B) and in those with a normal multimer pattern (atypical type 2B) (4.47+/-0.41 h and 4.87+/-0.9 h, respectively, vs. normal 15.53+/-2.17 h) due mainly to a greater VWF clearance. The half-life of large VWF multimers, explored by VWF collagen binding (VWF:CB) activity, was likewise reduced. The similarly reduced VWF half-life was also confirmed by the increase in the VWF propeptide ratio (a useful tool for exploring VWF survival) which was found to be the same in type 2B and atypical type 2B patients. The post-DDAVP drop in platelet count occurred in all patients lacking large multimers but not in those with a normal multimer pattern. A correlation was always found between pre- and/or post-DDAVP thrombocytopenia and the lack of large VWF multimers in type 2B VWD while these were unrelated to the reduced VWF half-life. CONCLUSIONS: In addition to demonstrating that a shorter VWF survival contributes to the type 2B and atypical type 2B VWD phenotype, our findings suggest that VWF clearance and proteolysis are independent phenomena. PMID- 20305139 TI - The response to imatinib and interferon-alpha is more rapid than the response to imatinib alone: a retrospective analysis of 495 Philadelphia-positive chronic myeloid leukemia patients in early chronic phase. AB - Before the introduction of imatinib, interferon alpha-based regimens were the gold standard for treatment of early chronic phase chronic myeloid leukemia patients. The combination of IFN-alpha with imatinib is currently being investigated in at least two large clinical trials, the German CML Study IV and the French SPIRIT trial. We reviewed the cytogenetic and molecular responses of 76 early chronic phase chronic myeloid leukemia patients who were treated with imatinib and interferon-alpha and of 419 early chronic phase chronic myeloid leukemia patients treated with imatinib alone front-line. The complete cytogenetic response rate was higher in the IM+IFN-alpha group than in the imatinib group at six months (60% vs. 42%; P=0.003), but not at 48 months (88% vs. 88%). The durability of the complete cytogenetic response was similar in the two groups with 94% and 91% of complete cytogenetic responders in continuous complete cytogenetic response at 48 months (P=0.56). The major molecular response rate was higher in the IM+IFN-alpha group at six months (58% vs. 34%; P=0.0001) and 12 months (67% vs. 47%; P=0.001) but not later on (65% vs. 57% at 48 months; P=0.25). Overall and progression free survival were comparable in the two groups; a significant trend to a better event free survival was observed in patients treated with PegIFNalpha (91% vs. 78%; P=0.02). These data suggest that the response to the combination treatment is more rapid. It is not yet known how much a rapid reduction will influence the longer-term overall and progression free survival, and the cure rate. PMID- 20305140 TI - Multidrug resistant Pseudomonas aeruginosa infection in children undergoing chemotherapy and hematopoietic stem cell transplantation. AB - Pseudomonas aeruginosa is one leading gram-negative organism associated with nosocomial infections. Bacteremia is life-threatening in the immunocompromised host. Increasing frequency of multi-drug-resistant (MDRPA) strains is concerning. We started a retrospective survey in the pediatric hematology oncology Italian network. Between 2000 and 2008, 127 patients with Pseudomonas aeruginosa bacteremia were reported from 12 centers; 31.4% of isolates were MDRPA. Death within 30 days of a positive blood culture occurred in 19.6% (25/127) of total patients; in patients with MDRPA infection it occurred in 35.8% (14/39). In the multivariate analysis, only MDRPA had significant association with infection related death. This is the largest series of Pseudomonas aeruginosa bacteremia cases from pediatric hematology oncology centers. Monitoring local bacterial isolates epidemiology is mandatory and will allow empiric antibiotic therapy to be tailored to reduce fatalities. PMID- 20305141 TI - Low molecular weight heparin for the treatment of retinal vein occlusion: a systematic review and meta-analysis of randomized trials. AB - Retinal vein occlusion is a frequent cause of visual loss for which few effective therapies are available. Anticoagulation with low molecular weight heparin might be of value in its treatment. We conducted a systematic review and meta analysis of randomized trials evaluating the effect of low molecular weight heparin in patients with retinal vein occlusion. Data sources included MEDLINE, EMBASE, HealthSTAR, the Cochrane Library, Lilacs, the Investigative Ophthalmology and Visual Science database and gray literature. Main outcome was the mean difference between the visual acuity measured at baseline and at six months expressed in the logMAR scale. Secondary outcome was a composite of any adverse ocular outcome including: worsening of visual acuity, visual fields or fluorescein angiography, or development of iris neovascularization, any neovascularization or neovascular glaucoma. Subgroup analyses for branch versus central retinal vein occlusion were conducted. We identified 1,084 references of which 3 studies comparing low molecular weight heparin with aspirin (229 evaluable patients) were included. Overall, the pooled mean visual acuity difference was -0.23 logMAR (95% CI -0.38, -0.09; P=0.002) in favor of low molecular weight heparin. Low molecular weight heparin was associated with a 78% risk reduction for developing any adverse ocular outcome (pooled RR 0.22; 95% CI 0.10, 0.46; P<0.001). In subgroup analyses benefits seemed lower in branch retinal vein occlusion. No increased vitreous hemorrhages were observed. In patients with retinal vein occlusion treatment with low molecular weight heparin seems to be associated with improvement in the visual acuity and less adverse ocular outcomes. These benefits might differ in patients with central as opposed to branch retinal vein occlusion. Further studies are required to confirm these findings and clarify its benefits in specific subgroups of patients before definitive recommendations can be made. PMID- 20305142 TI - Mechanism of human Hb switching: a possible role of the kit receptor/miR 221-222 complex. AB - BACKGROUND: The human hemoglobin switch (HbF-->HbA) takes place in the peri/post natal period. In adult life, however, the residual HbF (<1%) may be partially reactivated by chemical inducers and/or cytokines such as the kit ligand (KL). MicroRNAs (miRs) play a pivotal role in normal hematopoiesis: downmodulation of miR-221/222 stimulates human erythropoietic proliferation through upmodulation of the kit receptor. DESIGN AND METHODS: We have explored the possible role of kit/KL in perinatal Hb switching by evaluating: i) the expression levels of both kit and kit ligand on CD34(+) cells and in plasma isolated from pre-, mid- and full-term cord blood samples; ii) the reactivation of HbF synthesis in KL-treated unilineage erythroid cell cultures; iii) the functional role of miR-221/222 in HbF production. RESULTS: In perinatal life, kit expression showed a gradual decline directly correlated to the decrease of HbF (from 80-90% to <30%). Moreover, in full-term cord blood erythroid cultures, kit ligand induced a marked increase of HbF (up to 80%) specifically abrogated by addition of the kit inhibitor imatinib, thus reversing the Hb switch. MiR-221/222 expression exhibited rising levels during peri/post-natal development. In functional studies, overexpression of these miRs in cord blood progenitors caused a remarkable decrease in kit expression, erythroblast proliferation and HbF content, whereas their suppression induced opposite effects. CONCLUSIONS: Our studies indicate that human perinatal Hb switching is under control of the kit receptor/miR 221-222 complex. We do not exclude, however, that other mechanisms (i.e. glucocorticoids and the HbF inhibitor BCL11A) may also contribute to the peri/post-natal Hb switch. PMID- 20305144 TI - Josef Brudzinski and Vladimir Mikhailovich Kernig: signs for diagnosing meningitis. PMID- 20305143 TI - Impact of genomic risk factors on outcome after hematopoietic stem cell transplantation for patients with chronic myeloid leukemia. AB - BACKGROUND: Non-HLA gene polymorphisms have been shown to influence outcome after allogeneic hematopoietic stem cell transplantation. Results were derived from heterogeneous, small populations and their value remains a matter of debate. DESIGN AND METHODS: In this study, we assessed the effect of single nucleotide polymorphisms in genes for interleukin 1 receptor antagonist (IL1RN), interleukin 4 (IL4), interleukin 6 (IL6), interleukin 10 (IL10), interferon (IFNG), tumor necrosis factor (TNF) and the cell surface receptors tumor necrosis factor receptor II (TNFRSFIB), vitamin D receptor (VDR) and estrogen receptor alpha (ESR1) in a homogeneous cohort of 228 HLA identical sibling transplants for chronic myeloid leukemia. Three good predictors of overall survival, identified via statistical methods including Cox regression analysis, were investigated for their effects on transplant-related mortality and relapse. Predictive power was assessed after integration into the established European Group for Blood and Marrow Transplantation (EBMT) risk score. RESULTS: Absence of patient TNFRSFIB 196R, absence of donor IL10 ATA/ACC and presence of donor IL1RN allele 2 genotypes were associated with increased transplantation-related mortality and decreased survival. Application of prediction error and concordance index statistics gave evidence that integration improved the EBMT risk score. CONCLUSIONS: Non-HLA genotypes were associated with survival after allogeneic hematopoietic stem cell transplantation. When three genetic polymorphisms were added into the EBMT risk model they improved the goodness of fit. Non-HLA genotyping could, therefore, be used to improve donor selection algorithms and risk assessment prior to allogeneic hematopoietic stem cell transplantation. PMID- 20305145 TI - Prostate carcinoma metastatic to the stomach: report of two cases and review of the literature. AB - We report two cases of prostate carcinoma metastatic to the stomach. In the first case, the patient had indolent disease before presenting with gastric metastasis. The patient responded to treatment with resolution of gastrointestinal bleeding and other symptoms. In the second case, the patient developed aggressive prostate carcinoma while on immunosuppressive therapy following kidney transplant. His tumor became widely systemic, and he ultimately died of his disease. Although rare, the possibility of prostate carcinoma metastatic to the stomach should be considered when a patient with a history of prostatic adenocarcinoma presents with gastrointestinal symptoms. PMID- 20305146 TI - Treatment of urinary voiding dysfunction syndromes with spinal cord stimulation. AB - This case report presents the use of spinal cord stimulation (SCS) in a patient with urinary incontinence who had previously undergone trial and implantation of InterStim therapy (Medtronic Neurological, Minneapolis, MN). The patient also experienced bilateral lower extremity pain and low back pain related to post laminectomy syndrome. Having failed all conservative treatment, the patient underwent SCS trial and subsequent implantation. In the postoperative period using SCS therapy, the patient had excellent relief of urinary incontinence symptoms, along with relief of low back pain and bilateral lower extremity pain and was able to discontinue use of InterStim therapy. For this patient, SCS was effective in controlling the urinary voiding dysfunction symptoms, bilateral lower extremity pain and back pain. The use of SCS to treat urinary incontinence problems deserves further study to explore its therapeutic potentials. PMID- 20305147 TI - Large supratentorial cortical ependymoma in a child. PMID- 20305148 TI - Clinical effectiveness: Leadership in comparative effectiveness and translational research.: the 15th Annual HMO Research Network Conference, April 26-29, 2009, Danville, Pennsylvania. AB - The Health Maintenance Organization Research Network (HMORN), a consortium of 16 health care delivery systems with integrated research divisions, held its annual meeting in Danville, Pennsylvania in April of 2009 and was attended by more than 260 researchers and operational leaders from HMORN organizations, pharmaceutical companies, the National Cancer Institute, and the Agency for Healthcare Research and Quality. The 2009 meeting was held from April 26(th) to April 29(th) at the Henry Hood Center for Health Research, and was hosted by Geisinger Health System. The conference theme was "Clinical Effectiveness: Leadership in Comparative Effectiveness and Translational Research." This article provides some background on the network, its research activities, and the annual conference. This issue of Clinical Medicine & Research also includes selected scientific abstracts presented at the meeting. PMID- 20305266 TI - Identification of genetic network dynamics with unate structure. AB - MOTIVATION: Modern experimental techniques for time course measurement of gene expression enable the identification of dynamical models of genetic regulatory networks. In general, identification involves fitting appropriate network structures and parameters to the data. For a given set of genes, exploring all possible network structures is clearly prohibitive. Modelling and identification methods for the a priori selection of network structures compatible with biological knowledge and experimental data are necessary to make the identification problem tractable. RESULTS: We propose a differential equation modelling framework where the regulatory interactions among genes are expressed in terms of unate functions, a class of gene activation rules commonly encountered in Boolean network modelling. We establish analytical properties of the models in the class and exploit them to devise a two-step procedure for gene network reconstruction from product concentration and synthesis rate time series. The first step isolates a family of model structures compatible with the data from a set of most relevant biological hypotheses. The second step explores this family and returns a pool of best fitting models along with estimates of their parameters. The method is tested on a simulated network and compared with state of-the-art network inference methods on the benchmark synthetic network IRMA. PMID- 20305267 TI - LOTUS, a new domain associated with small RNA pathways in the germline. AB - We describe here LOTUS, a hitherto uncharacterized small globular domain, which was identified using sensitive sequence profile analysis. The LOTUS domain is found in germline-specific proteins that are present in the nuage/polar granules of germ cells. TDRD5 and TDRD7, two mammalian members of the germline Tudor group, possess three copies of the LOTUS domain in their extreme N-termini. The Tudor domains of these proteins bind symmetric dimethyl arginines present on the germ cell-specific Piwi proteins, which form a particular clade of Argonaute proteins. Piwi proteins interact with a specific class of non-coding RNAs [piwi interacting RNAs (piRNAs)] and play a key role in the repression (silencing) of transposons and possibly other germline-specific functions. A LOTUS domain is also present in the Oskar protein, a critical component of the pole plasm in the Drosophila oocyte, which is required for germ cell formation. LOTUS domains are found in various proteins from metazoans and plants, are often associated with RNA-specific modules and are likely to adopt a winged helix fold. This suggests a germline-specific role in the mRNA localization and/or translation or a specific function toward piRNAs. PMID- 20305268 TI - ProBiS algorithm for detection of structurally similar protein binding sites by local structural alignment. AB - MOTIVATION: Exploitation of locally similar 3D patterns of physicochemical properties on the surface of a protein for detection of binding sites that may lack sequence and global structural conservation. RESULTS: An algorithm, ProBiS is described that detects structurally similar sites on protein surfaces by local surface structure alignment. It compares the query protein to members of a database of protein 3D structures and detects with sub-residue precision, structurally similar sites as patterns of physicochemical properties on the protein surface. Using an efficient maximum clique algorithm, the program identifies proteins that share local structural similarities with the query protein and generates structure-based alignments of these proteins with the query. Structural similarity scores are calculated for the query protein's surface residues, and are expressed as different colors on the query protein surface. The algorithm has been used successfully for the detection of protein protein, protein-small ligand and protein-DNA binding sites. AVAILABILITY: The software is available, as a web tool, free of charge for academic users at http://probis.cmm.ki.si. PMID- 20305269 TI - CoP: a database for characterizing co-expressed gene modules with biological information in plants. AB - Using a large dataset (10 022 assays) obtained from public plant microarray databases, we developed the CoP database for associating co-expressed gene modules with biological information such as gene ontology terms and, if available, metabolic pathway names. The Confeito algorithm developed previously in our laboratory, which is suitable to calculate the interconnectivity between genes in co-expressed gene network, was applied to extract co-expressed gene modules. The database includes the gene modules for Arabidopsis thaliana (thale cress) and seven crops, Glycine max (soybean), Hordeum vulgare (barley), Oryza sativa (rice), Populus trichocarpa (poplar), Triticum aestivum (wheat), Vitis vinifera (grape) and Zea mays (maize). AVAILABILITY: The CoP database is available at: http://webs2.kazusa.or.jp/kagiana/cop0911/. PMID- 20305270 TI - Curators of the world unite: the International Society of Biocuration. PMID- 20305271 TI - Characterization of the reactions of starch branching enzymes from rice endosperm. AB - To our knowledge the present paper shows for the first time the kinetic parameters of all the three starch branching enzyme (BE) isozymes, BEI, BEIIa and BEIIb, from rice with both amylopectin and synthetic amylose as glucan substrate. The activities of these BE isozymes with a linear glucan amylose decreased with a decrease in the molar size of amylose, and no activities of BEIIa and BEIIb were found when the degree of polymerization (DP) of amylose was lower than at least 80, whereas BEI had an activity with amylose of a DP higher than approximately 50. Detailed analyses of debranched products from BE reactions revealed the distinct chain length preferences of the individual BE isozymes. BEIIb almost exclusively transferred chains of DP7 and DP6 while BEIIa formed a wide range of short chains of DP6 to around DP15 from outer chains of amylopectin and amylose. On the other hand, BEI formed a variety of short chains and intermediate chains of a DP 4 cm) locally invasive tumors (P < 0.05). MMP9 expression was significantly decreased in tumors with regional metastasis, whereas increased expression of ADAM8 was noted in the metastatic tumors (P < 0.001 for both). CONCLUSIONS: These findings suggest the HNSCC degradome as a valuable source of diagnostic, predictive, and prognostic molecular markers for these malignant tumors. PMID- 20305302 TI - The volume-mortality relation for radical cystectomy in England: retrospective analysis of hospital episode statistics. AB - OBJECTIVES: To investigate the relation between volume and mortality after adjustment for case mix for radical cystectomy in the English healthcare setting using improved statistical methodology, taking into account the institutional and surgeon volume effects and institutional structural and process of care factors. DESIGN: Retrospective analysis of hospital episode statistics using multilevel modelling. SETTING: English hospitals carrying out radical cystectomy in the seven financial years 2000/1 to 2006/7. PARTICIPANTS: Patients with a primary diagnosis of cancer undergoing an inpatient elective cystectomy. MAIN OUTCOME MEASURE: Mortality within 30 days of cystectomy. RESULTS: Compared with low volume institutions, medium volume ones had a significantly higher odds of in hospital and total mortality: odds ratio 1.72 (95% confidence interval 1.00 to 2.98, P=0.05) and 1.82 (1.08 to 3.06, P=0.02). This was only seen in the final model, which included adjustment for structural and processes of care factors. The surgeon volume-mortality relation showed weak evidence of reduced odds of in hospital mortality (by 35%) for the high volume surgeons, although this did not reach statistical significance at the 5% level. CONCLUSIONS: The relation between case volume and mortality after radical cystectomy for bladder cancer became evident only after adjustment for structural and process of care factors, including staffing levels of nurses and junior doctors, in addition to case mix. At least for this relatively uncommon procedure, adjusting for these confounders when examining the volume-outcome relation is critical before considering centralisation of care to a few specialist institutions. Outcomes other than mortality, such as functional morbidity and disease recurrence may ultimately influence towards centralising care. PMID- 20305303 TI - [Mood, mood fluctuations and depression: role of the circadian rhythms]. AB - The statement that circadian rhythmicity is an important component of mood regulation as well as a drive of mood disorders is supported by a growing body of evidence. Diurnal rhythms of the positive and negative components of mood as well as of the level of arousal depend on the circadian phase, the homeostatic sleep regulatory mechanisms and the harmonic interaction of the circadian and homeostatic processes. The chronopathological symptoms which are typical in depression and explain the blunted mood of depressive patients are of the phase advance and phase-delay type characterized by a misalignment between the circadian rhythms and the sleep-wake schedules, best described by the phase-angle alterations. The abnormal phase angle between circadian rhythms and the timing of the sleep period could emerge from an interaction of the chronotypes and other constitutional factors with adverse environmental effects (inadequate zeitgebers) leading to a disharmony between the diurnal components of mood regulation and consequent extreme mood states. The aim of the chronotherapies of depression and of other affective disorders is that of resynchronizing the circadian rhythms or in other words to reconstitute the harmony between these subsystems. Pharmacological approaches, lifestyle changes and specific chronotherapeutic interventions might help to achieve this goal. PMID- 20305304 TI - [Dopamine D4 receptor hypoxia sensitivity and child psychiatric disorders]. AB - Attention-deficit hyperactivity disorder (ADHD) is one of the most frequent child psychiatric problems with a complex genetic and environmental background. According to the prevailing view, main factors of the disorder are prefrontal dopamine deficiency and incomplete central dopaminergic functioning. Twin studies suggest substantial heritability in the background of the disease, and the studied candidate genes involve components of the dopamine system. Moreover, various noxious pre- and perinatal environmental impacts have been implicated in the pathogenesis of ADHD. Here we review experimental results from epidemiological, tissue and animal studies that assigned a causal role to fetal hypoxia in the development of ADHD and pointed out that the dopaminergic neurotransmission is sensitive to hypoxia. Allelic variants of the D4 dopamine receptor (DRD4) are well characterized risk factors of ADHD. Recently we have reported that hypoxia enhanced the promoter activity of DRD4 gene several fold. These observations suggest that the effect of hypoxia on the dopaminergic neurotransmission might be an important factor in the pathomechanism of ADHD. PMID- 20305305 TI - Epilepsy and dependence. AB - Epilepsy is relatively frequent neurological condition. Its prevalence is assumed to be about 1%, and it would be interesting to see how many of these people have comorbid substance dependence disorder. The manifestation of epilepsy exhibits a seizure-like condition with typical neurological and psychical symptoms, which are induced by pathological electric discharges in brain. The population of addicts is known to have higher prevalence of seizures, found not only in alcohol abusers, but also in illicit drug users. The aim of our paper is to give an overview of the prevalence rates of this serious health condition in patients with substance dependence treated at the OLUP NPO, Predna Hora. The author compares two groups of patients: with and without the epileptic seizures. Alcohol addicts prevailed in both groups. Each 8th treated dependent patient had at least one epileptic seizure. Nearly the same percent of dependent patients in both groups (43,6% vs. 40,9%) holds a driving license, thus they probably also drive a motor vehicle. Is there any person who would initiate withdrawal of driving license from such patients? Frequent somatic diseases in more than one half of the group with seizures (more than 62%) highlight the fact that this group of patients requires thorough and financially probably more demanding health care. PMID- 20305306 TI - [The effects of duloxetine on beta-actin stress response in rat brain]. AB - Depression is a frequent prodromal symptom of Alzheimer's disease (AD). Stress factors play an important role in the etiopathology of both diseases, since increased corticosteroid levels caused by chronic stress indirectly induce neuronal damage. The aim of our experiments was to evaluate the changes induced by stress in the transcription of amyloid precursor protein (APP), mitogen activated protein kinase-1 (MAPK-1) and beta-actin, of which the latest plays a leading role in synaptic plasticity. Additionally we intended to examine how duloxetine - a serotonin-norepinephrin reuptake inhibitor type antidepressant - would modify the stress-induced changes. Wistar rats were exposed to immobilization stress for five hours daily through 21 days, while part of the animals received 45 mg/bwkg of duloxetine. At the end of the third week total RNA was purified from the cortex and hippocampus. The amount of beta-actin, APP and MAPK-1 mRNA was determined by real time PCR method. On protein level, semiquantitative measurement was performed by Western blot. The expression of beta-actin mRNA in the animals exposed to stress was four times as intense as in the control group. The increase in the beta-actin mRNA levels was repressed by the duloxetine treatment. In the case of APP and MAPK-1 no changes were detected. According to the Western blot results, the antidepressant treatment slightly, the drug along with the stress treatment strongly decreased the amount of the beta actin protein. Our findings indicate that antidepressant treatment with duloxetine could play a protective role against the chronic stress-induced changes in the nervous system, such as disorders of synaptic plasticity, and the consequent cognitive dysfunctions in case of both affective disorders and AD. PMID- 20305307 TI - [Complex hallucination (visual-auditory) during coadministration of tramadol and clarithromycin]. AB - Acute manifestations of various psychopathological symptoms require detailed differential diagnostic procedure, since their cause is found to be somatic in several cases. These adverse events during the treatment are often the side effects of the prescribed drugs or drug-drug interactions. In the presented case report, the patient had complex visual-auditory hallucinations two days after the initiation of tramadol-clarithromycin coadministration and these transient symptoms were repeated for two days. After the interruption of the administration of these drugs, the symptoms disappeared in two days, without the administration of any kind of psychotropics. These two drugs by themselves may cause hallucinations, and because both of them are metabolized by the same enzyme (CYP 3A4) in the liver, symptoms were worsened by the drug-drug interaction. The reason of this effect is that tramadol is the substrate and clarithromycin is the inhibitor of the CYP 3A4 enzyme. Medical examination results (physical examination, ECG, blood samples, CT scan, EEG) could not be causally related to the symptoms. Suspected risk factors were the old age of the patient, the condition of his brain and the interactions with other previously prescribed drugs. This case report calls the attention of clinicians to the fact that in vitro drug-drug interactions in vivo can produce clinical manifestations more often then taken into account. PMID- 20305308 TI - [Difficulties in changing drugs--from clozapine to aripiprazole in ambulatory care]. AB - Although there are well-established psychiatric procedures available concerning switching of antipsychotic drugs, in practice we often face a situation where we have to consider not only the patient's demands, but also requests from relatives. In this article we describe a case where we encountered this situation. Our patient was a 48-year-old married man suffering from paranoid schizophrenia with extreme obesity. We had to consider the modification of the antipsychotic treatment because of the patient's persistent residual symptoms (significant lack of initiative, serious under-motivation, emotional plainessness, considerable passivity) his overweight and its consequences (metabolic syndrome). In our paper we describe the psychoeducational process and the clozapine/aripiprazol switch. PMID- 20305309 TI - Pathogenesis of HIV infection: total CD4+ T-cell pool, immune activation, and inflammation. AB - Recent studies have yielded important findings on the pathogenesis of HIV infection. HIV infection leads to immune dysfunction through CD4+ T-cell depletion (immunodeficiency) and immune activation (immunosuppression). In vivo imaging studies of nonhuman primates indicate that the total body pool of CD4+ T cells may provide more accurate quantitation of immune depletion in HIV infection than the peripheral blood CD4+ count. Immune activation appears to be driven by both a homeostatic response to CD4+ cell depletion and an inflammatory response to HIV infection. The evidence is mounting that ongoing inflammation and coagulation account for the increased risk of serious nonopportunistic events in patients with HIV infection. Studies in long-term nonprogressors indicate that the HIV-specific immune responses in these patients are distinguished by clonal expansions of antigen-specific CD8+ T cells. Additional study of the precise mechanisms that allow immunologic control of infection in these patients may contribute to development of vaccines and immune-based therapies. This article summarizes a presentation made by H. Clifford Lane, MD, at the International AIDS Society-USA continuing medical education program held in May 2009 in Chicago. The original presentation is available as a Webcast at www.iasusa.org. PMID- 20305310 TI - Medical interventions for addictions in the primary care setting. AB - Primary care physicians treating HIV-infected patients should not be afraid or reluctant to engage in medication-assisted treatment for substance dependence. Effective medications are available for many types of substance addictions, including buprenorphine for opioid dependence, disulfiram for cocaine dependence, bupropion for methamphetamine dependence, and naltrexone for alcohol dependence. Physician use of medications coupled with encouragement to adhere to all aspects of treatment including counseling and other psychosocial interventions can produce substantial rewards in terms of keeping patients involved in their HIV care and improving overall patient health and functioning. This article summarizes a presentation made by R. Douglas Bruce, MD, MA, MSc, at the 12th Annual Clinical Conference for the Ryan White HIV/AIDS Program held in October 2009 in Dallas, Texas. The original presentation is available as a Webcast at www.iasusa.org. PMID- 20305311 TI - Dermatologic manifestations of HIV in Africa. AB - Dermatologic disease is common in HIV-infected individuals, and clinicians caring for patients with HIV infection or AIDS in Africa are routinely confronted with skin problems in their patients. Scarce access to dermatologic specialty care and limited educational resources describing the unique clinical characteristics of HIV-related skin disease can make diagnosing and treating skin diseases a challenge in Africa. This article describes common HIV-related dermatologic conditions in Africa and their differential diagnoses and includes treatment strategies that are likely to be available locally. It is not meant to be comprehensive but rather to serve as a practical resource to aid practitioners by providing images of common conditions and describing distinctive clinical presentations of common conditions. PMID- 20305312 TI - Aging of the liver graft and functional quality in the absence of recurrent disease: a 10 year histological follow-up. AB - BACKGROUND: Although considerable information has been acquired concerning the function of older donor liver grafts it remains unclear how long these organs may fare well in their "cumulative life span". As graft challenge due to recurrent underlying disease can best be eliminated and controlled in patients transplanted for alcoholic liver disease (ALD) we analysed liver biopsies of ALD patients during a 10-year follow-up with special emphasis on donor age and parenchymal quality. MATERIAL/METHODS: Biopsies were taken from 271 patients 1, 3, 5, 10 years after LT. Specimen were analysed and staged concerning inflammation, rejection, fatty involution, and fibrosis/cirrhosis. Donor characteristics were recorded along with clinical and serological parameters, immunosuppressive protocols, rejection episodes, and patient and graft survival. RESULTS: 1, 3, 5 years after LT >80% of patients displayed only minimal fibrosis. In the further course fibrosis rates increased among all patients, with slightly more fibrosis for recurrent drinkers. Donor age did not influence fibrosis progression, long term patient or graft survival. Regardless of alcohol abuse survival was excellent 5 years after LT, after 10 years abstinent patients did significantly better (82%;68%; p=0.017. CONCLUSIONS: LT for ALD offers excellent long-term survival with minimal histological alteration, especially in abstinent patients. Aged organs generate adequate function in ALD recipients. PMID- 20305313 TI - Orthotopic liver transplantation: the first experience and results of the Vilnius University Hospital Santariskiu Klinikos. AB - BACKGROUND: Liver transplantation has become the treatment of choice for chronic and acute end-stage liver failure as well as for selected cases of malignancies and metabolic disorders. We report our first experience of the orthotopic liver transplantation. MATERIAL/METHODS: Between 2005 and 2008 16 cadaveric orthotopic liver transplantations in 16 adults (12 males, 4 females, mean age 44 years) were performed. Main indications for orthotopic liver transplantation were cholestatic liver disease (31%), viral-induced cirrhosis (25%), alcoholic liver disease (19%), hepatocellular carcinoma associated with hepatitis virus infection (13%), autoimmune cirrhosis (6%), cryptogenic acute liver failure (6%). Mean follow-up was 15 month (range: 4 days - 43 month). RESULTS: Intraabdominal haemorrhage was observed in 6 patients (37.5%). Vascular complications were observed in 3 patients (18.75%). Biliary complication were observed in 3 patients (18.75%). Overall 1 year patient survival was 87,5%. Four (25%) patients died during follow up. All patients died because of sepsis and multiorgan system failure. CONCLUSIONS: Our first results showed that secret of successful liver transplantation is perfect interdisciplinary team approach, including selection of the recipient and timing of transplantation, the operative procedure itself, prevention and treatment of complications, the perioperative anaesthesiological and intensive-care management, and careful follow up after transplantation. PMID- 20305315 TI - Chronic kidney disease in prevalent orthotopic heart transplant recipients using a new CKD-EPI formula. AB - BACKGROUND: Heart transplantation is an established treatment for advanced heart failure. However, chronic kidney disease (CKD) is an important long-term complication of all forms of organ transplantation other than renal. It has been shown that a GFR <60 ml/min is predictive of premature cardiovascular death. MATERIAL/METHODS: The aim of this study was to assess the prevalence of kidney dysfunction in heart transplant recipients using a new CKD-EPI formula in a cohort of 169 prevalent patients (mean age 53.30+/-13.80 years). RESULTS: Mean serum creatinine in this population was 1.71+/-1.10 mg/dl, Serum creatinine was normal (<1.4 mg/dL in males and <1.2 mg/dL in females) in 45.4% of the patients. According to the Cockcroft-Gault formula, stage 2 CKD (i.e.GFR 60-89 ml/min) was demonstrated in 79 patients (46.75%), stage 3 CKD (i.e. GFR 30-59 ml/min) in 49 patients (29.00%) and stage 4 CKD (i.e. GFR 15-29 ml/min) in 15 patients (8.88%). According to MDRD formula stage 2 CKD was found in 36 patients (21.30%), stage 3 CKD was found in 79 patients (46.75%) and stage 4 in 27 patients (15.98%). According to new CKD-EPI formula, stage 2 CKD was found in 35 patients (20.71%), stage 3 CKD in 79 patients (46.75%) and stage 4 in 28 patients (16.57%). According to the creatinine clearance stage 2 CKD was found in 61 patients (36.09%), stage 3 CKD in 63 patients (37.28%) and stage 4 in 19 (11.24%) patients. Clinically significant CKD (GFR <60 ml/min) was found in 37.88-63.91% depending on the formula used to estimate the GFR. Normal kidney function was found in 27 patients (15.98%) according to MDRD formula, in 27 patients (15.98%) according to new CKD-EPI formula, in 26 patients (15.38%) according Cockcroft Gault formula and 26 patients (15.38%) on the basis of 24-hours creatinine clearance. CONCLUSIONS: We conclude that the prevalence of CKD is high in heart transplant recipients. Evaluation of renal function is important in order to select the appropriate strategy to reduce the cardiovascular risk. New CKD-EPI formula seems to more accurate in assessment kidney function that previously used, however, it merits further studied and validation against gold standard of isotope GFR measurement. PMID- 20305314 TI - The influence of cardiac rhythm type and frequency on the prognosis of severe heart failure patients initially qualified for heart transplantation. AB - BACKGROUND: Atrial fibrillation (AF) is the most common arrhythmia among patients (pts) with heart failure and has significant influence on survival. AIM OF THE STUDY: to assess prognosis of pts with refractory heart failure (HF) qualified for heart transplantation (HTX). MATERIAL/METHODS: 872 pts (107 W and 765 M) were qualified for HTX between Dec 2003 and Oct 2007. Patient's death or super urgent heart transplantation were considered the end point in Kaplan-Meier survival curves. RESULTS: 680 pts were on sinus rhythm (SR) and 192(22.0%) had atrial fibrillation (AF). During follow-up (1-1464 days, mean 550 days) 155 pts (17.7%) died, 17.65% with SR and 18.23% with AF (ns). EF - mean 21,6 (SR) and 21,8 (FA), NYHA 3,1 (SR), NTproBNP- mean 3635, 4 (SR) and 4349,4 (FA), Arronson - mean 7,8 (SR) and 7,7 (FA). There were no significant differences between groups. We analyzed influence of heart rate (Kaplan-Maier method) on survival. The pts were divided according to HR: gr.I <70/min, gr II 71-89/min, gr III >90/min. The shortest survival rate was noticed in group III. There was no difference in survival between group I and II. CONCLUSIONS: The prognosis for patients qualified for heart transplant does not depend on the type of the dominant cardiac rhythm (atrial fibrillation or sinus rhythm). The prognosis is significantly better for those patients whose basic, resting heart rate does not exceed 90 bpm regardless of the rhythm type. PMID- 20305316 TI - The safety of hem-o-lock clips at donor nephrectomies. AB - BACKGROUND: Hem-o-lock (polymer) vascular clips have been used over a long period for vascular control at donor nephrectomies. With our study, safety of hem-o-lock clip use at donor nephrectomies (conventional donor nephrectomy, transabdominal donor nephrectomy and retroperitonoscopic donor nephrectomy) has been evaluated. MATERIAL/METHOD: A total of 883 cases, consisting of conventional donor nephrectomy, transabdominal donor nephrectomy and retroperitonoscopic donor nephrectomy, performed between May 2006 and August 2009 were retrospectively evaluated. Of all cases, 803 were performed conventional donor nephrectomy, 85 were performed endoscopic donor nephrectomy. Five patients who had first undergone endoscopic donor nephrectomy had conversion operations. RESULTS: Vascular control at renal pedicle were obtained either with hem-o-lock clip ot vascular clamps. Cases with conventional donor nephrectomy were divided into two subgroups. Group I: cases which had transfixation sutures with 5.0 prolene in order to prevent clip separation after hem-o-lock clip use; Group II: cases without transfixation sutures. Only hem-o-lock sutures were used at laparoskopic and retroperitonoscopic techniques. Large and X-large clip and were used for renal arteries and two X-large clips were used for renal vein. CONCLUSIONS: The most ideal method for vascular control at donor nephrectomy is controversial. Use of transfixation and hem-o-lock clips at conventional donor nephrectomy may be an alternative method. However for all three methods and at both groups, none of the cases who had undergone nephrectomy had bleeding or donor loss caused by hem-o lock clips at intraoperative, perioperative anf postoperative periods. For this reason, we believe that use of hem-o-lock clips is a safe and reliable method for vascular control at donor nephrectomies. PMID- 20305317 TI - Variant anatomy of renal arteries in a Kenyan population. AB - BACKGROUND: Variant anatomy of renal arteries is important in renal transplant, vascular reconstruction, and uroradiological procedures. The variations show ethnic and population differences. Data from Africans are scarce and altogether absent for Kenyans. OBJECTIVE: To describe patterns of origin, trajectories and branching of renal arteries in a Kenyan population. STUDY DESIGN AND SETTING: Descriptive cross-sectional study conducted in the Department of Human Anatomy, University of Nairobi. MATERIAL/METHODS: Three hundred and fifty six kidneys from 178 cadavers and postmortem specimens were used in the study. Aorta, renal arteries and kidneys were exposed by dissection. Number, trajectories, level of branching, number of branches and point of entry into the kidney were recorded. Data was analyzed using SPSS version 16.0, and presented using macrographs, tables, and bar charts. RESULTS: Additional arteries occurred in 14.3% of the cases. In 82.4% of these, there was one additional artery. Fifty nine point five per cent of the double renal arteries were parallel and 7.1% crossed. Of the 305 single arteries, 76.4% showed hilar, 21.6% prehilar and 2% intraparenchymal branching. In the hilar branching, ladder type was present in 65% and fork type in 35%. Bifurcation and trifurcation were present in 59.6% and 33.1% respectively. Polar arteries were present in 16.9% cases. CONCLUSIONS: Over 14% of the Kenyan population may have additional renal arteries while more than 20% show early branching. Several trajectories and hilar branching patterns exist which renal transplant surgeons and radiologists should be aware of to avoid inadvertent vascular injury. PMID- 20305318 TI - The assessment of PFA-100 test for the estimation of blood loss in renal transplantation operation. AB - BACKGROUND: Platelet dysfunction is well known factor that may play a role in bleeding diathesis in uremia. In recent years, Platelet Function Assay 100 (PFA 100) was introduced to measure platelet function. The purpose of this study was to determine whether an abnormal PFA-100 is an accurate predictor of bleeding in dialysis patients undergoing renal transplantation (RTx). MATERIAL/METHODS: We included 98 dialysis patients undergoing RTx operation. PFA-100 test measuring collagen/epinephrine (Col/EPI) and collagen/adenosine 5'-diphosphate (Col/ADP) closure was performed in each patients after induction of anesthesia. We compared intraoperative blood loss measured by gravimetric method during RTx operation method between patients with normal Col/EPI and Col/ADP closure times (group 1, n= 51) and with prolonged Col/EPI and Col/ADP closure times (group 2, n=47). RESULTS: Intraoperative blood loss calculated by gravimetric method was 273+/-50 ml in the group 1 and 303+/-109 ml in the group 2 (p>0.05). Blood loss in gross formula was 356+/-87 ml in the group 1 and 450+/-99 ml in group 2 (p>0.05). CONCLUSIONS: Assessment of platelet function with preoperative measurement of PFA 100 in RTx patients is not an effective method for estimating the risk of blood loss in the intraoperative and postoperative periods. PMID- 20305319 TI - Unsuccessful attempt of forearm transplantation--case report. AB - BACKGROUND: The technique of hand transplantation is similar to that of hand replantation. Although the rate of failure of hand replantation tantamount to 15% on average, depending mostly on mechanism of amputation, until now no data have been published concerning the failure of attempts of hand transplantation. CASE REPORT: A 42-year-old male is presented who was the recipient of a hand transplant. The patient had an amputation of his left, dominant forearm (result of a circular-saw accident) 8 years prior to the transplantation. He was generally healthy, very dedicated to the operation. The limb was obtained in another hospital from a 49-year-old woman, victim of an accident and multi visceral donor.The donor was matched for blood group (0 positive), bone size, texture, with the recipient. There was 4 HLA antigen mismatch; the lymphocytotoxic cross-match was negative. The operation was performed in a sequence as follows: bones--muscles--nerves--veins--arteries--skin. The induction IT consisted of Simulect, Prograff, Cell-Cept, and steroids; the pharmacotherapy was standard as for a forearm replantation. The cold ischemia time was 9 hours. Soon after the transplantation the disturbances of blood circulation in the transplanted forearm were to be seen. High doses of macromolecular heparin were applied resulting in temporary improvement. During following hours despite various precautions the symptoms of ischemia of the hand up to 1/3 distal part of the forearm dramatically increased. The revision (performed 12 hrs after completing the transplantation) proved a massive thrombosis of hand arteries, and a large clot of the radial artery in locus of it's cannulation for invasive blood pressure measurement. The limb had to be re-amputated. As it came clear the arterial catheter was removed 6 hours prior to procurement. CONCLUSIONS: The hand transplant are not free from non-immunological typical vascular complications. The arterial catheters should not be applied in limbs destined for procurement. PMID- 20305320 TI - Toxic tacrolimus blood levels with rifampin administration in a renal transplant recipient. AB - BACKGROUND: Induction of the hepatic and intestinal cytochrome P450-3A4 system and intestinal P-glycoprotein is an unavoidable consequence of rifampin administration which requires substantial increase in tacrolimus dose when given concurrently. Chronic diarrhea is known to precipitate tacrolimus toxicity irrespective of its cause in renal transplant recipients. CASE REPORT: A 28 years old lady had a second renal transplant when she was 15 years old which is functioning normally. She was maintained on prednisolone, azathioprine, omeprazole and tacrolimus. Tacrolimus was maintained on therapeutic levels (5-7 ng/ml). She developed pyrexia of unknown origin associated with chronic diarrhea. Detailed investigations didn't reach any definite diagnosis. Antituberculous drugs including rifampin were started emperically. During the first four months of antituberculous treatment diarrhea worsened and unexpected high tacrolimus trough blood levels were observed requiring successive dose reduction from 7 mg/day up to 0.5 mg every other day with rise of serum creatinine from 100 to 140 umol/l. Tacrolimus was changed to low dose sirolimus and renal function gradually improved to its baseline while still on rifampin treatment. CONCLUSIONS: We conclude that chronic diarrhea may cause toxic tacrolimus blood levels even in presence of rifampin, this would be due to its significant cytochrome P450-3A4 and P-glycoprotein enzyme inhibitory effect. PMID- 20305321 TI - Leuconostoc pseudomesenteroides blood stream infection following liver transplantation. AB - BACKGROUND: Leuconostoc spp. are vancomycin resistant Gram positive lactobacilli. Little is known about their significance in transplant recipients. CASE REPORT: A 64-year-old female liver transplant recipient developed Leuconostoc sepsis originating from a bile leak after extended exposure to vancomycin. The infection was readily controlled clindamycin, however, the patient died later on unrelated to the infection. Five articles on Leuconostoc infections in transplant patients were found in PubMed including two liver recipients with intraabdominal infection due to biliary complications and four stem cell recipients with sepsis. CONCLUSIONS: Leuconostoc spp. should be considered pathogens in transplant recipients who are exposed to vancomycin. PMID- 20305322 TI - Occult donor metastatic adenocarcinoma. Contribution of the forensic autopsy. A case report. AB - BACKGROUND: The transmission of malignancies from the organ donor to the recipients is an uncommon complication, but it can be fatal. Older donors may increase the risk of tumor transmission. A forensic autopsy will help identify diseases that might be transmitted to the recipient. CASE REPORT: Donor was a 75 year-old man with traumatic brain injury caused by an accidental fall, which led to brain death. He had no previous cancer history. The forensic autopsy conducted on the following day revealed a suspicious spot in the lung, on which a biopsy was done. Histological examination confirmed the presence of a metastatic adenocarcinoma in the lung 7 days after both kidneys had been transplanted. After notifying the transplant team, both recipients underwent an early transplant nephrectomy. 15 months later, no signs of malignancy have been detected in the recipients and so they have received a new transplant. CONCLUSIONS: Conducting a forensic autopsy on donors deceased as a result of a fatality offers an additional opportunity to detect previously undiagnosed malignancies. Any suspicious lesion found that could compromise transplant viability should be notified to the transplant team notwithstanding the pathologist's legal requirements. This case shows the need for an exhaustive donor evaluation, including, in selected cases, the performance of an autopsy. PMID- 20305323 TI - Factors affecting catch-up growth after liver transplantation in children with cholestatic liver diseases. AB - Growth retardation is one of the most prominent consequences of childhood cholestatic liver diseases. The pathogenesis of malnutrition is multifactorial and includes reduced calorie intake, fat malabsorption, abnormal protein metabolism, and increased energy expenditure. Poor growth is a typical feature of biliary atresia, cystic fibrosis, progressive familial intrahepatic cholestasis and Alagille syndrome. In some of these features it is not only directly related to impaired nutrient absorption. Liver transplantation is required if liver disease progresses to liver failure - improved nutritional status is achieved within weeks after surgery. Still, patients with Alagille syndrome present with only slight catch-up growth after transplantation, while patients with PFIC and biliary atresia grow significantly.
PMID- 20305324 TI - Clinical characteristics and hematologic responses to Imatinib in patients with chronic phase myeloid leukemia (CML) at Cipto Mangunkusumo Hospital. AB - AIM: To analyze the clinical characteristics of patients with chronic phase CML and evaluate complete hematologic responses (CHR) and overall survival (OS) after treatment with Imatinib. METHODS: This is a cross sectional study using retrospective medical record of patients with chromosome Philadelphia positive and/or BCR-ABL positive chronic phase CML at the polyclinic of Teratai Department of Internal Medicine Cipto Mangunkusumo National Hospital during 2003-2008. In a period of 6 years, we included 53 patients with chromosome Philadelphia positive and/or BCR-ABL positive chronic phase CML. Patients were administered Imatinib 400 mg daily and then evaluation of clinical characteristics and complete blood count + differential count were performed every 2 weeks until CHR achieved at 3 months as defined by white cells count < 10,000/mm3, platelet count > 450,000/mm3, and non palpable spleen. RESULTS: The median age was 37 years (16-67 years). Males were slightly more frequent than females (29 v.s. 24) with ratio of 1.2:1. Thirty three percent of patients had splenomegaly. The vast majority (60%) of patients had previous treatment with Hydroxyurea. The laboratory features were: median of hemoglobin level was 10.0 g/dL (6.3-16.6 g/dL), median of white cell count was 13,300/uL (1900-621,000/uL), and median of platelet count was 424,000/uL (108,000-4,400,000/uL). Median of basophils was 1.6% (0%-20%) and 88% of patients had <5% blasts in bone marrow. CONCLUSION: A CHR was achieved in 74% of patients and overall survival during the study was 66%. The most common adverse events were: nausea, myalgia, hypopigmentation of the skin, anemia, thrombocytopenia, and neutropenia. PMID- 20305325 TI - VEGF expression and desmoplastic reaction as potential progressive factors in young patients with colorectal cancer. AB - AIM: To compare the expression of VEGF-A and desmoplastic reaction of colorectal cancer between the young aged and old aged patients excluding the stage of tumor. METHODS: Our study was a retrospective study on VEGF-A expression and desmoplastic reaction in pathology anatomy specimens of patients with colorectal cancer at young age (less than 40 years of age) and older age (more than equal 60 years of age). The samples had been taken since 2001 until 2008 and the sample size for each group was 42 samples for young age and 36 samples for older age subjects. To carry out the examination of VEGF expression, our study utilized the immunohistochemistry method. In addition, desmoplastic reaction as a preliminary study was evaluated by using routine HE staining. To recognize the difference of VEGF-A expression and the degree of desmoplastic reaction in young aged and older aged patients with colorectal cancer, a Chi-Square test was performed. The statistics was considered as significant when p value <0.05. RESULTS: Forty-two patients were at younger age (< or =40 years) and 36 patients were at older age (> or =60 years), with characteristics of them 37 males and 41 females. Tumor grading was performed based on WHO criteria. Ten subjects with high-grade tumor and 32 subjects with low-grade in the young age group; while in the older age group, there were 9 subjects with high-grade tumor and 27 subjects with low grade tumor. In young age, there was twice greater likelihood to have pronounced desmoplastic reaction compared to the older age (OR = 2.1). CONCLUSION: The VEGF A expression in younger and older age was nearly the same; however, there was significant difference of desmoplastic reaction in younger aged patients compared to the older aged. There was also comparable correlation between strong positive VEGF-A expression and strong desmoplastic reaction in young patients with colorectal cancer. PMID- 20305326 TI - ACE gene insertion/deletion polymorphism among patients with type 2 diabetes, and its relationship with metabolic syndrome at Sardjito Hospital Yogyakarta, Indonesia. AB - AIM: To know the frequencies of insertion/deletion polymorphism in the angiotensin-converting enzyme (ACE) gene among patients with type 2 diabetes and its relationship with metabolic syndrome at Sardjito Hospital Yogyakarta. METHODS: We examined 69 patients with type 2 diabetes at Sardjito Hospital Yogyakarta, divided 2 groups based on ATP III criteria of metabolic syndrome. To determine the ACE genotype of the patients, a genomic DNA fragment on intron 16 of the ACE gene was amplified by polymerase chain reaction (PCR) using a forward primer 5'-CTG GAG ACC ACT CCC ATC CTT TCT-3' and reverse primer 5'-GAT GTG GCC ATC ACA RTC GTC AGA T-3'. II genotype 1 band on 490 bp (homozigot), DD genotype 1 band on 190 bp (homozigot) and ID genotype 2 band (heteroduplex) on 490 bp and 190 bp were separately detected on a 3% agarose gel containing ethidium bromide. RESULTS: Of 69 patients with type 2 diabetes, there were 51 females (73.91%) and 18 males (26.09%). Subjects with metabolic syndrome were 49 patients (71.02%) while without metabolic syndrome were 20 patients (28.98%). Subjects with II, DD, ID genotype were 57.97%, 23.19% and 18.84% respectively. The male subjects with II, DD, ID genotype were 55.56%, 27.78% and 16.67% respectively, and the female subject II, DD ID genotype were 58.82%, 21.57% and 19.61% respectively. The association between ACE I/D polymorphism and metabolic syndrome in type 2 diabetes, was not significant (p=0.204). CONCLUSION: The frequency of ACE I/D polymorphism among type 2 diabetes are 57.97% II, 23.19% DD, 18.84% ID. There is no association between metabolic syndrome and the component of metabolic syndrome and varians of the ACE gene among the type 2 diabetes patients. PMID- 20305327 TI - Expression of hypoxia-inducible factor-1alpha (HIF-1alpha) related to oxidative stress in liver of rat-induced by systemic chronic normobaric hypoxia. AB - AIM: To observe the expression of hypoxia-inducible factor-1alpha (HIF-1alpha) and its relation with oxidative stress in liver of rats induced by systemic chronic normobaric hypoxia. METHODS: Twenty five male, 6-8 weeks old rats were induced by systemic hypoxia. Rats were divided randomly into 5 groups (n = 5 per group). The control group was exposed to normal environment while the hypoxic groups were kept in hypoxic chamber (10% O(2)) for 1, 3, 7, and 14 days. Animals were sacrificed, the liver isolated and homogenized. Total RNA was extracted and isolated and expression of HIF-1alpha mRNA was measured by real-time RT PCR using Pffafl method. Malondialdehyde (MDA), product of lipid peroxidation was measured by tBARS assay. Glutathione (GSH), an abundant endogenous antioxidant in the liver tissue was measured using Ellman method. RESULTS: Study showed that expression of HIF-1alpha mRNA was increased in group treated for 1 day of hypoxic condition, and then decreased in group treated for 3, 7 and 14 days of hypoxic condition related with duration of hypoxic condition. The MDA level in liver tissue increased, but not significant in all groups of hypoxic condition and persisted along duration time of hypoxic condition. The GSH level was decreased significantly (p<0.005) in all groups of hypoxic condition. CONCLUSION: Expression of HIF-1alpha mRNA was higher at the early phase of hypoxia and decreased as hypoxia continued. Systemic hypoxia induction caused increased ROS formation during hypoxia, and depleted the GSH concentration in the liver. Oxidative stress present in liver of rat was induced by systemic hypoxia. PMID- 20305328 TI - Urine osmolality in the elderly. AB - AIM: Investigation was done in the institutionalized elderly in order to know the value of urine osmolality in this population. METHODS: Cross sectional study was done in the government institutionalized elderly that localized in South Jakarta. By using simple random sampling, 50 elderly people were chosen from all of the residents in this institutionalized elderly aged more than 60 years. They were excluded if they had diabetes mellitus, abnormal cortisol (reference range of morning cortisol, 5-25 ug/dL), potassium less than 3 meq/L, chronic diarrhoe, congestive heart failure, nephrotic syndrome, and cirrhosis of the liver, and also if they were in manitol or diuretic treatment, and not cooperative. All of these data were analyzed with descriptive analysis and comparative T-test of two non-related groups. RESULTS: There were 28 elderly peoples consisted of 13 males and 15 females participated in this study. The mean of the urine osmolality was 581 +/- 174 mosmol/Kg. The mean of the urine osmolality in the female group (657.33 +/- 126.54 mosmol/kg) was significantly higher than in the male group (p = 0.01). CONCLUSION: The urine osmolality in the elderly is high and the so called normal value is 407-755 mosmol/Kg. Further study is needed to investigate the lowest urine osmolality value as the diagnostic tool of hyponatremia due to water excretion disorder in the elderly. PMID- 20305329 TI - A randomized, controlled, double-blind trial of the adjunct use of Clebopride in polyethylene glycol electrolyte (PEG) solution for colonoscopy preparation. AB - AIM: To study the benefit of Clebopride as an adjuvant in polyethylene glycol electrolyte (PEG) solution for colonoscopy preparation. METHODS: Eighty one adult patients who underwent colonoscopy examination were recruited in this randomized double blind controlled study. First group received PEG and placebo, whereas second group received PEG and Clebopride. Two litres of PEG was taken at night before colonoscopy. The acceptability and tolerability of bowel preparation were assessed through interview method. The efficacy of bowel preparation was assessed using Aronchick's Criteria. RESULTS: In terms of acceptability, 64 patients (31 patients from placebo group vs 33 patients from Clebopride group) were able to drink two litres of PEG solution. Sixty patients (29 patients from placebo group and 31 patients from Clebopride group) were willing to accept PEG solution for their next bowel preparation. On the term of tolerability, nausea, abdominal distension, and borborygmus were more frequent in the placebo group (34.2% vs 27.9%; 44.7% vs 32.6%; 26.3% vs 4.6% respectively). However, only the difference at the incidence of borborygmus that was statistically significant (p<0.05). On the terms of efficacy, both groups showed a comparable bowel preparation quality with 88.4% of bowel preparation in Clebopride group and 81.6% of bowel preparation in placebo group were optimal (p = 0.585). CONCLUSION: The adjunct use of Clebopride in PEG solution for colonoscopy preparations tends to increase the acceptability, tolerability, and efficacy. The presence of borborygmus was significantly lower in the Clebopride group. PMID- 20305330 TI - Hashimoto's thyroiditis following Graves' disease. AB - Both Graves' disease and chronic thyroiditis (Hashimoto's thyroiditis) are autoimmune diseases of thyroid gland. Graves' disease is caused by stimulation of TSH receptor located on the thyroid gland by an antibody, which is known as TSH receptor antibody (TRAb). Furthermore, this may lead to hyperplasia and hyperfunction of the thyroid gland. On the contrary, the cause of Hashimoto's thyroiditis is thought due to a TSH stimulation-blocking antibody (TSBAb) which blocks the action of TSH hormone and subsequently brings damage and atrophy to thyroid gland. Approximately 15-20% of patients with Graves' disease had been reported to have spontaneous hypothyroidism resulting from the chronic thyroiditis (Hashimoto's disease). Pathogenesis for chronic thyroiditis following anti-thyroid drug treatment in patients with Graves' disease remains unclear. It has been estimated that chronic thyroiditis or Hashimoto's disease, which occurs following the Graves' disease episode is due to extended immune response in Graves' disease. It includes the immune response to endogenous thyroid antigens, i.e. thyroid peroxidase and thyroglobulin, which may enhance lymphocyte infiltration and finally causes Hashimoto's thyroiditis. We report four cases of chronic thyroiditis (Hashimoto's disease) in patients who have been previously diagnosed with Graves' hyperthyroidism. In three cases, Hashimoto's thyroiditis occurs in 7 to 25 years after the treatment of Grave's disease; while the other case has it only after few months of Grave's disease treatment. The diagnosis of Hashimoto's disease (chronic thyroiditis) was based on clinical manifestation, high TSHs level, positive thyroid peroxidase antibody and thyroglobulin antibody, and supported by positive results of fine needle aspiration biopsy. Moreover, the result of histopathological test has also confirmed the diagnosis in two cases. All cases have been successfully treated by levothyroxine treatment. PMID- 20305331 TI - Nutritional carcinogenesis. AB - Human beings are often being exposed to carcinogenic factors during their life, some of which are the nutritional factors. From the mechanistic view, nutritional factors are classified into genotoxic and non-genotoxic agents. Genotoxic agent begins their action at the DNA level, causing DNA damage through several mechanisms, e.g. gene point mutations, deletions and insertions, recombinations, rearrangements and amplifications, as well as chromosomal aberrations. Most genotoxic agents are micro components of nutrition, i.e. polycyclic aromatic hydrocarbon (PAH) or heterocyclic amines (HCAs), aflatoxin, and N-nitrosamine. Non-genotoxic agents are less defined in their modes of action, but they are presumed to indirectly affect the cell through tumor promoters. These agents are generally macro components, e.g. high fat. Moreover, epigenetic factors, including changes in the DNA methylation pattern, and peroxidation process resulting reactive oxygen species (ROS), are also known to cause cancer. On the other hand, it is also well recognized that diet and nutrition contain components that can reduce the risk of cancer, in some cases by decreasing the effects of food mutagens, or through carcinogen detoxification, or protection of DNA from electrophilic carcinogen. Thus nutritionally related cancer ultimately develops from an imbalance of carcinogenesis and anti-carcinogenesis process. PMID- 20305332 TI - Clinical manifestation of oral candidiasis in a HIV patient. PMID- 20305333 TI - Malaria treatment by using artemisinin in Indonesia. AB - Report on resistance of old malarial drug treatment (eg. chloroquine, sulphadoxine-pyrimethamine, and quinine) in the last decade has become concerned, affecting more than 25% provinces in Indonesia. Such a situation leads to a decision made by the Department of Health through commission meetings of malarial experts or known as komisi ahli malaria (KOMLI) to change the strategy of malaria drug treatment by using ACT (artemysinin combination treatment). As a treatment for any infection, a tendency of using drug combination has a strong role against resistance and preventing resistance to primary drug. Artemisinin is a sesquiterpene lactone of anti-malaria drug which is characterized by its blood schizonticides nature to P. falciparum and P. vivax. It has been developed from an ancient Chinese traditional drug for patient with fever, which is made from an extract of Artemesia annua L (qinghao) and has been used since thousand of years ago and was found by Chinese researchers in 1971. Artemisinin has been used for mild malaria as combination drug (ACT) and for severe malaria by using intra-vena or intra-muscular artesunate, or by using artemether for intra-muscular purpose only. Patients with malaria should have their blood slides to be examined on day 2, 3, and day 7, 14, 21, and 28. Patients who are not hospitalized and could not return on day 2 (48 hours following the initial treatment), may return on day 3. For those who got early or late treatment failure, another treatment should be provided. Treatment failure shall be defined in two criteria which are early and late treatment failure. The treatment for each patients with severe malaria should be performed as general treatment, symptomatic treatment, administration of anti-malaria drug, and treatment on complication. PMID- 20305334 TI - Out-of-field photon dose following removal of the flattening filter from a medical accelerator. AB - The aim of this paper is to determine the effect of removing the flattening filter from a linear accelerator on the out-of-field photon dose. A Monte Carlo model was used to simulate 6 MV and 18 MV photon beams from a Varian 2100 accelerator with the flattening filter in place and with it removed. The out-of field photon doses and composition (head leakage, patient scatter and collimator scatter) were calculated from square open fields in a water tank as a function of distance from central axis, field size and depth. The out-of-field doses resulting from intensity-modulated radiation therapy to the prostate at 6 MV were also calculated, with and without the flattening filter, to sensitive organs in an anthropomorphic Rando phantom. Removal of the flattening filter reduced the out-of-field dose near the treatment field (<3 cm from the field edge) because of decreased collimator scatter. It increased the out-of-field dose at intermediate distances from the field edge (3-15 cm) because of increased patient scatter. At greater distances, the out-of-field dose was decreased because of reduced head leakage. For the clinical treatment examined, the out-of-field dose was generally reduced following removal of the flattening filter, particularly at large distances from the treatment field. Removal of the flattening filter may be advantageous by reducing the out-of-field dose to the patient. This could contribute to reducing the long-term risk of secondary malignancies. In general, however, the out-of-field dose depends on treatment and patient parameters, and a reduction may not always be achievable. PMID- 20305335 TI - In vivo preclinical evaluation of the accuracy of toroidal-shaped HIFU treatments using a tumor-mimic model. AB - The pig is an ideal animal model for preclinical evaluation of HIFU treatments, especially in the liver. However, there is no liver tumor model available for pigs. In this work, we propose to study an in vivo tumor-mimic model as a tool for evaluating if a sonographycally guided HIFU treatment, delivered by a toroidal-shaped device dedicated for the treatment of liver metastases, is correctly located in the liver. One centimeter tumor-mimics were created in liver tissues. These tumor-mimics were detectable on ultrasound imaging and on gross pathology. Two studies were carried out. First, an in vivo study of tolerance at mid-term (30 days, 10 pigs) revealed that tumor-mimics are suitable for studying HIFU treatments at a preclinical stage, since local and biological tolerances were excellent. The dimensions of the tumor-mimics were reproducible (diameter at day 0: 9.7 +/- 2.0 mm) and were the same as a function of time (p = 0.64). A second in vivo study was carried out in ten pigs. Tumor mimics were used as targets in liver tissues in order to determine if the HIFU treatment is correctly located in the liver. A procedure of extensive HIFU ablation using multiple HIFU lesions juxtaposed manually was then tested on eight tumor-mimics. In 88% of the cases (seven out of eight), tumor-mimics were treated with negative margins (>or=1 mm) in all directions. On average, negative margins measured 10.0 +/- 6.7 mm. These tumor-mimics constitute an excellent reference for studying in vivo the accuracy of HIFU therapy in the liver. PMID- 20305336 TI - Mechanistic simulation of normal-tissue damage in radiotherapy--implications for dose-volume analyses. AB - A radiobiologically based 3D model of normal tissue has been developed in which complications are generated when 'irradiated'. The aim is to provide insight into the connection between dose-distribution characteristics, different organ architectures and complication rates beyond that obtainable with simple DVH-based analytical NTCP models. In this model the organ consists of a large number of functional subunits (FSUs), populated by stem cells which are killed according to the LQ model. A complication is triggered if the density of FSUs in any 'critical functioning volume' (CFV) falls below some threshold. The (fractional) CFV determines the organ architecture and can be varied continuously from small (series-like behaviour) to large (parallel-like). A key feature of the model is its ability to account for the spatial dependence of dose distributions. Simulations were carried out to investigate correlations between dose-volume parameters and the incidence of 'complications' using different pseudo-clinical dose distributions. Correlations between dose-volume parameters and outcome depended on characteristics of the dose distributions and on organ architecture. As anticipated, the mean dose and V(20) correlated most strongly with outcome for a parallel organ, and the maximum dose for a serial organ. Interestingly better correlation was obtained between the 3D computer model and the LKB model with dose distributions typical for serial organs than with those typical for parallel organs. This work links the results of dose-volume analyses to dataset characteristics typical for serial and parallel organs and it may help investigators interpret the results from clinical studies. PMID- 20305337 TI - The treatment effect of the burn wound healing by electrolyticreduction ion water lotion. AB - A 2-year-and-4-month-old girl suffered a burn to the neck due to boiling water. She was examined at another hospital, and recommended to undergo dermatoplasty. Thirteen days after injury, she consulted our hospital. A wide skin defect was observed around the neck, and a third-degree burn was diagnosed. Conservative treatment using electrolyticreduction ion water (ERI) lotion, antibiotics/steroid combination ointment, and vitamin A/E ointment was performed without dermatoplasty. Treatment of the burn was started with the application of ERI lotion, antibiotics/steroid combination ointment, and vitamin A/E ointment to the wound 3 times a day combined with wrap therapy. The lysis of necrotic tissue and granulation began 1 week after the beginning of treatment. After 2 weeks, the necrosed skin had completely lysed, satisfactory granulation tissue began to form and blood supply improved. Regeneration of the skin was noted at 1-3 months after the beginning of treatment. Complete epithelialization was observed after 4 months, but hypertrophic cicatrization and pigmentation began to occur. After 26 months, capillary growth was observed, cicatrix became inconspicuous, pigmentation disappeared, and the burn almost completely healed. In conclusion, in this patient, the process of tissue repair after burn injury progressed smoothly, and healing was achieved without leaving hypertrophic cicatrix, keloid scar, or pigmentation. Our experience suggested that even third-degree burns can be treated using only external therapy with ERI lotion, antibiotics/steroid combination ointment, and vitamin A/E ointment without dermatoplasty. PMID- 20305338 TI - A study of the relationship between mental health and menstrual abnormalities in female middle school students from postearthquake Wenchuan. AB - The present field investigation sought to explore the relationship between mental health and abnormal menstruation in female middle school students from post earthquake Wenchuan following the 2008 Sichuan earthquake (the earthquake's epicenter was in Wenchuan Couty, Sichuan Province). A total of 587 female middle students from post-earthquake Wenchuan were given the PCL-C, SCL-90, and a menstruation questionnaire. Outcomes were measured by diagnostic criteria. The general incidence of PTSD was 60.8%, and D symptoms were the most prevalent PTSD symptoms (49.6%). Of symptoms indicated by the Symptom Checklist, obsessive compulsive traits were most prevalent (94.6%), followed by interpersonal sensitivity (91.9%). The incidence of abnormal menstruation was 76.6%. Incidence of abnormal menses among students who screened positive for PTSD was significantly higher than among students who did not (chi2 = 4.015, p = 0.045). The incidence of abnormal menses was higher among students who screened positive for somatization, obsessive-compulsive traits, phobic anxiety, and diet and sleep disorders than among those who did not (p < 0.05). In conclusion, there was a relationship between mental health and physical health in female middle school students in a post-earthquake area. A higher incidence of abnormal menstruation may occur in students with PTSD, somatization disorder, obsessive-compulsive disorder, phobic anxiety, and diet and sleep disorders. Therefore, psychological intervention is particularly necessary for female students who have survived a natural disaster like an earthquake. PMID- 20305339 TI - Rapid increase in Japanese life expectancy after World War II. AB - Japanese life expectancy increased by about 13.7 years during the first decade after World War II, despite the country's post-war poverty. Although it is known that medical progress explains part of this increase, roles of non-medical factors have not been systematically studied. This study hypothesizes that non medical factors, in addition to medical factors, are associated with the rapid increase in life expectancy in Japan. We analyzed the time trends of potential explanatory factors and used regression analysis with historical data from the Ministry of Internal Affairs and Communications' Historical Statistics of Japan during the period between 1946 and 1983. Time trends analysis revealed that the rapid increase in life expectancy preceded the dramatic growth of per capita Gross Domestic Product (GDP) by 10 years. In education, the nearly universal enrollment in elementary schools and increased advancement to upper secondary schools for both sexes were associated with better health. Regarding legislation, 32 health laws were passed in the first decade after the war and these laws were associated with improved health. Using regression analysis, we found that the enrollment rate in elementary schools, the number of health laws, and expansion of community-based activity staff were significantly associated with the increased life expectancy during the first decade after World War II. To conclude, in addition to medical factors, non-medical factors applied across the country, particularly education, community-based activities and legislation were associated with the rapid increase in Japanese life expectancy after World War II. PMID- 20305340 TI - Bioavailability and biological activity of liquisolid compact formula of repaglinide and its effect on glucose tolerance in rabbits. AB - This study is an extension of the previous enhancement of dissolution properties of repaglinide using liquisolid compacts. The development and validation of a highperformance liquid chromatography (HPLC) assay for the determination of repaglinide concentration in rabbit plasma for pharmacokinetic studies is described. Repaglinide optimizing formula was orally administered to rabbits and blood samples were used to determine the pharmacokinetic parameters of repaglinide, which were compared to pharmacokinetic parameters of marketed tablets (Novonorm 2 mg). Also, to investigate the biological activity of this new formula, in comparison with the commercial product, oral glucose tolerance tests (OGTT), area under the curve and insulin levels were studied. Moreover, we studied the efficacy and safety of this new formula in several potencies (0.5, 1, and 2 mg) and blood glucose, insulin, kidney and liver functions. The relative bioavailability of repaglinide from its liquisolid compact formula was found to be increased significantly in comparison to that of the marketed tablet. In regard to urea and creatinine, no significant change was recorded after the administration of the commercial and the three potencies of the new formulation compared with the control group. Similarly, in liver function tests (serum glutamic pyruvic transaminase, SGPT), there were no changes observed in its level. Regarding insulin levels, the commercial formula increased insulin levels insignificantly (3.52% change) while the new formula increased the insulin level significantly with a percent change of 37.6%. The results of the glucose tolerance test showed that the blood glucose level was decreased significantly after the commercial drug (percent change, 18.1%) while in groups treated with the new formulation the decrease was highly significant (p < 0.01) with a percent change of 29.98%. The change in area under the curve for blood glucose was significantly higher in the commercial drug plus glucose load than in the new formulation plus glucose load group (p < 0.05) in the periods of 30-45 min and 45 60 min. Furthermore, the new repaglinide formulation significantly decreased blood glucose levels more than the commercial formula. PMID- 20305341 TI - Evaluation of estrogen receptor alpha, estrogen receptor beta, progesterone receptor, and cKIT expression in desmoids tumors and their role in determining treatment options. AB - The present study evaluates the protein expression of estrogen receptor alpha (ERalpha), estrogen receptor beta (ERbeta), progesterone receptor (PR) and cKIT in a wide number of desmoids tumors and their role in determining treatment options. Fifty-nine cases classified as muscle aponeurotic fibromatosis were selected. Samples were grouped by tumor location in: head and neck, extremity and abdominal/trunk; type of resection of the primary tumor (complete resection with adequate margins, marginal resection and resection with inadequate margins); type of treatment (exclusive surgery, surgery followed by radiation therapy and surgery followed by tamoxifen or cyclooxygenase inhibitor). A tissue microarray (TMA) was built and the immunohistochemical reactions were performed against ERalpha, ERbeta, PR, and c-kit. All cases were negative for ERalpha, PR and c KIT. 53/59 cases were positive for ERbeta. No significant difference was observed among clinical variables and the ERbeta status. The estimated 5 and 10 year local recurrence free survival (LRFS) for the patients with complete or marginal resection was 75% and 75%, respectively. Tumor location (p = 0.006) and type of resection (p = 0.001) were predictive of local relapse in the univariate analysis. All patients treated with post-operative tamoxifen were LRFS (p = 0.035). Head and neck and extremities lesions showed higher recurrence rates compared to abdominal/trunk lesions. Marginal resection was associated with local recurrence. In conclusion, although this is a retrospective study, the results presented can contribute to better understanding of the mechanisms under desmoid tumor development and can propose tamoxifen as a therapeutic option to be tested in prospective trials. PMID- 20305342 TI - The healing effect of electrolytic-reduction ion water on burn wounds. AB - We prepared a lotion using electrolytic-reduction ion water (ERI), and evaluated the healing effects of this lotion (ERI lotion) on burn wounds. Third degree burn wounds were induced in the mouse dorsal skin, and ERI lotion or physiological salt (PS) lotion was applied to the wounds from immediately after injury [ERI (+) group and ERI (-) group as a control group, respectively]. The burn wound area was measured, and its serial changes were evaluated. In addition, histological examination of the burn wound site (on day 3) was performed. Comparison of the ERI (+) and (-) groups showed a significant reduction in the burn wound area in the former. Histological examination confirmed many interstitial spaces, blood vessels, and lymphatic vessels in the subcutaneous tissue in the ERI (-) compared with the ERI (+) group. These results suggest the promotion of burn wound healing by ERI lotion. PMID- 20305343 TI - Compliance with the triage protocols. PMID- 20305344 TI - Crystal growth and twinned crystal structure of Sr2CaWO6. AB - Single crystals of Sr(2)CaWO(6) have been prepared by sintering at high temperature. Powder samples were compressed into rods and heated up to 1953 K. This seems a promising new route for further studies of the structure and physical properties of double perovskites. The structural model of Sr(2)CaWO(6) includes a quantitative description of the twinning shown by the diffraction pattern that should be present in almost any single-crystal specimen for this type of compound. PMID- 20305345 TI - Superspace description of the homologous series Ga2O3(ZnO)m. AB - A unified description for the structures of the homologous series Ga(2)O(3)(ZnO)(m), gallium zinc oxide, is presented using the superspace formalism. The structures were treated as a compositely modulated structure consisting of two subsystems. One is constructed with metal ions and the other with O ions. The ideal model is given, in which the displacive modulations of ions are well described by the zigzag function with large amplitudes. Alternative settings are also proposed which are analogous to the so-called modular structures. The validity of the model has been confirmed by refinements for phases with m = 6 and m = 9 in the homologous series. A few complex phenomena in real structures are taken into account by modifying the ideal model. PMID- 20305346 TI - Modulation functions of incommensurately modulated Cr2P2O7 studied by the maximum entropy method (MEM). AB - The maximum entropy method (MEM) has been used to determine electron density in superspace of incommensurately modulated chromium pyrophosphate from X-ray diffraction data measured by Palatinus et al. [(2006), Acta Cryst. B62, 556-566]. Chromium pyrophosphate, Cr(2)P(2)O(7), contains ordered regions (83% of the volume) and regions with disorder. Analysis of the MEM density has allowed the determination of the displacive modulation functions within ordered regions. The disordered regions can be described as the alternate occupation of two conformations of the pyrophosphate group and two positions of the chromium atom, with occupational probabilities that depend continuously on the phase of modulation t. A structure model based on the interpretation of the MEM density provides a fit to the diffraction data of the same quality as the model given by Palatinus et al. (2006). The failure to find a model that better fits the data is attributed to the intrinsic inaccuracy of approximately 0.01 A for positions derived from the MEM and to the difficulties in constructing an appropriate model for the anharmonic ADPs and their modulation functions from electron densities. PMID- 20305347 TI - Mullite-type Ga4B2O9: structure and order-disorder phenomenon. AB - Ga(4)B(2)O(9), an aluminium-free mullite-type compound, was prepared by a boric acid flux method and its structure was determined using powder X-ray diffraction techniques, in combination with transmission electron microscopy, solid-state (11)B MAS-NMR and IR spectroscopies. GaO(6) octahedra share edges in a trans manner forming one-dimensional chains along the b direction, and the chains are further cross-linked by GaO(5), BO(3) and BO(4) groups into a three-dimensional mullite-type structure. The disorder of the inter-chain groups results in a small unit cell for Ga(4)B(2)O(9) compared with that for Al(4)B(2)O(9), an ordered compound with a superstructure. By deconstructing the structure of Ga(4)B(2)O(9), we were able to identify the fundamental building units and their linking rules which can be used to reconstruct the ordered and disordered structures. For Ga(4)B(2)O(9), we found that the structure is intrinsically disordered within the ac plane, but ordered along the b axis. The three-dimensional structure can then be constructed by stacking the disordered ac sheets along the b axis ((1/2)b) with a (1/2)a shift. The fundamental building units and exclusivity rules identified in this gallium borate mullite may also be useful for understanding other related mullite phases. The structure analysis applying the proposed method is used to recognize the structural features of Al(4)B(2)O(9) and Al(18)B(4)O(33). PMID- 20305348 TI - Two new silicate structures based on a rhodesite-type heteropolyhedral microporous framework. AB - Two new members of the mero-plesiotype rhodesite series [Sr(2)Na(2)(Si(8)O(19)).4H(2)O, abbreviated as TR09; SrNa(4)(Si(8)O(19)).4H(2)O, TR10] have been hydrothermally synthesized in Teflon-lined autoclaves at 503 K and structurally characterized using X-ray diffraction single-crystal data. The crystal structures were solved by direct methods and refined to R = 0.021 [TR09; 3317 reflections with I(o) > 2sigma(I(o))] and R = 0.033 [TR10; 5007 reflections with I(o) > 2sigma(I(o))]. Both structures are based on a rhodesite-type microporous heteropolyhedral framework, where two types of channels are within the double silicate layer that alternates with an ;octahedral' O sheet. The large Sr(2+) cation constrains to the roughly ellipsoidal shape of the channels. The H(2)O molecules are located both in the O sheets and in the channels, where they are loosely hydrogen bonded. The crystal-chemical features that allow flexibility to the rhodesite-type microporous heteropolyhedral framework and make it interesting for possible technological applications are discussed. PMID- 20305349 TI - New RE microporous heteropolyhedral silicates containing 4(1)5(1)6(1)8(2) tetrahedral sheets. AB - Four heteropolyhedral microporous silicates, A(3)RESi(6)O(15).2.25H(2)O, crystallizing in the Cmm2 space group and based on 4(1)5(1)6(1)8(2) tetrahedral sheets [A(3) = Na(2.74)K(0.26), RE = Ce, abbreviated as TR05; TR06: A(3) = Na(2.72)K(0.28), RE = La; TR07: A(3) = Na(3), RE = La; TR08: A(3) = Na(2.74)(H(3)O)(0.26), RE = La(0.68)Eu(0.32)] have been hydrothermally synthesized in Teflon-lined autoclaves at 503 K and structurally characterized using X-ray diffraction single-crystal data. Except for TR05, diffraction data have been collected on {001} twins by merohedry. The four structures are isotypic and based on strongly corrugated 4(1)5(1)6(1)8(2) silicate sheets interconnected along [010] by seven-coordinated RE polyhedra to form a microporous heteropolyhedral framework. The framework is crossed by three systems of ellipsoidal channels that host H(2)O molecules and alkaline ions. The channels run either parallel or perpendicular to the silicate sheets; the largest effective channel width is 4.7 x 2 A. In TR08 some (H(3)O)(+) replaces alkalis. Although the H atoms have not been localized, the configuration of the hydrogen bonding has been deduced from bond lengths and angles. PMID- 20305350 TI - Re-investigation of the structure and crystal chemistry of the Bi2O3-W2O6 'type (Ib)' solid solution using single-crystal neutron and synchrotron X-ray diffraction. AB - Single crystals of composition Bi(35.66)W(4.34)O(66.51) (or Bi(8.2)WO(15.3), bismuth tungsten oxide), within the type (Ib) solid-solution region of the Bi(2)O(3)-WO(3) system, were synthesized using the floating-zone furnace method. Synchrotron X-ray and neutron single-crystal diffraction data were used to confirm the previously tentative assignment of the room-temperature space group as I4(1). Fourier analysis of the combined X-ray and neutron datasets was used to elucidate and refine fully the cation and anion arrays for the first time. The mixed cation site M1 is shown to be coordinated by eight O atoms in an irregular cube when M = Bi, and by six O atoms in an octahedron when M = W. The resulting disorder in the average structure around M1 is discussed in the context of experimentally observed oxide-ion conductivity. PMID- 20305351 TI - Inorganic structures in space group P31m; coordinate analysis and systematic prediction of new ferroelectrics. AB - The 62 entries listed in ICSD release 2009/1 under polar space group P31m correspond to 31 families of inorganic crystal structures, some with only one member. Coordinate analysis reveals, over a wide confidence range, 11 of these families as ferroelectric candidates. One includes the well known improper ferroelectric GASH (guanidinium aluminum sulfate hexahydrate), [(C(NH(2))(3))Al(SO(4))(2)(H(2)O)(6)], another the previously predicted ferroelectric CsNO(3) phase II. Those remaining include K(3)Nb(3)B(2)O(12), the minerals schairerite, galeite and lizardite 1T, LaNi(5)D(6) and gamma CaNi(5)D(6.1), Ca(OCl)(2)Ca(OH)(2), [N(CH(3))(4)](2)Mo(3)S(13), Li(17)Ag(3)Sn(6) and Cs(3)As(5)O(9). Candidate selection is based upon detecting an approach by the reported atomic arrangement to the symmetry of a corresponding nonpolar supergroup. A further 13 families are typified by their reduced predictive properties, with four others likely to remain polar at higher temperatures and the remaining three noted as having a unit cell larger than reported or a misassigned space group. The primary sources of uncertainty in structurally based predictions of ferroelectricity are the reliability of the underlying structural determination and the upper limit assigned to the cationic displacement magnitudes required to achieve supergroup symmetry. PMID- 20305352 TI - Maximum entropy method and charge flipping, a powerful combination to visualize the true nature of structural disorder from in situ X-ray powder diffraction data. AB - In a systematic approach, the ability of the Maximum Entropy Method (MEM) to reconstruct the most probable electron density of highly disordered crystal structures from X-ray powder diffraction data was evaluated. As a case study, the ambient temperature crystal structures of disordered alpha-Rb(2)[C(2)O(4)] and alpha-Rb(2)[CO(3)] and ordered delta-K(2)[C(2)O(4)] were investigated in detail with the aim of revealing the ;true' nature of the apparent disorder. Different combinations of F (based on phased structure factors) and G constraints (based on structure-factor amplitudes) from different sources were applied in MEM calculations. In particular, a new combination of the MEM with the recently developed charge-flipping algorithm with histogram matching for powder diffraction data (pCF) was successfully introduced to avoid the inevitable bias of the phases of the structure-factor amplitudes by the Rietveld model. Completely ab initio electron-density distributions have been obtained with the MEM applied to a combination of structure-factor amplitudes from Le Bail fits with phases derived from pCF. All features of the crystal structures, in particular the disorder of the oxalate and carbonate anions, and the displacements of the cations, are clearly obtained. This approach bears the potential of a fast method of electron-density determination, even for highly disordered materials. All the MEM maps obtained in this work were compared with the MEM map derived from the best Rietveld refined model. In general, the phased observed structure factors obtained from Rietveld refinement (applying F and G constraints) were found to give the closest description of the experimental data and thus lead to the most accurate image of the actual disorder. PMID- 20305353 TI - 1,1'-Fc(4-C6H4CO2Et)2 and its unusual salt derivative with Z' = 5, catena [Na+]2[1,1'-Fc(4-C6H4CO2-)2].0.6H2O [1,1'-Fc = (eta5-(C5H4)2Fe]. AB - The neutral diethyl 4,4'-(ferrocene-1,1'-diyl)dibenzoate, Fe[eta(5)-(C(5)H(4))(4 C(6)H(4)CO(2)Et)](2) (I), yields (II) (following base hydrolysis) as the unusual complex salt poly[disodium bis[diethyl 4,4'-(ferrocene-1,1'-diyl)dibenzoate] 0.6 hydrate] or [Na(+)](2)[Fe{eta(5)-(C(5)H(4))-4-C(6)H(4)CO(2)(-)}(2)].0.6H(2)O with Z' = 5. Compound (I) crystallizes in the triclinic system, space group P1, with two molecules having similar geometry in the asymmetric unit (Z' = 2). The salt complex (II) crystallizes in the orthorhombic system, space group Pbca, with the asymmetric unit comprising poly[decasodium pentakis[diethyl 4,4'-(ferrocene-1,1' diyl)dibenzoate] trihydrate] or [Na(+)](10)[Fe{eta(5)-(C(5)H(4))-4-C(6)H(4)CO(2)( )}(2)](5).3H(2)O. The five independent 1,1'-Fc[(4-C(6)H(4)CO(2))(-)](2) dianions stack in an offset ladder (stepped) arrangement with the ten benzoates mutually oriented cisoid towards and bonded to a central layer comprising the ten Na(+) ions and three water molecules [1,1'-Fc = eta(5)-(C(5)H(4))(2)Fe]. The five dianions differ in the cisoid orientations of their pendant benzoate groups, with four having their -C(6)H(4)- groups mutually oriented at interplanar angles from 0.6 (3) to 3.2 (3) degrees (as pi...pi stacked C(6) rings) and interacting principally with Na(+) ions. The fifth dianion is distorted and opens up to an unprecedented -C(6)H(4)- interplanar angle of 18.6 (3) degrees through bending of the two 4-C(6)H(4)CO(2) groups and with several ionic interactions involving the three water molecules (arranged as one-dimensional zigzag chains in the lattice). Overall packing comprises two-dimensional layers of Na(+) cations coordinated mainly by the carboxylate O atoms, and one-dimensional water chains. The non polar Fc(C(6)H(4))(2) groups are arranged perpendicular to the layers and mutually interlock through a series of efficient C-H...pi stacking contacts in a herringbone fashion to produce an overall segregation of polar and non-polar entities. PMID- 20305354 TI - Change in electronic structure in a six-coordinate copper(II) complex accompanied by an anion order/disorder transition. AB - A variable-temperature crystallographic study of [Cu(L(OH))(2)][ClO(4)](2).2(CH(3))(2)CO [L(OH) = 2,6 bis(hydroxyiminomethyl)pyridine] between 30 and 300 K is presented. The complex exhibits an unusual electronic structure at room temperature with a {d(z(2))}(1) ground state, corresponding to an axially compressed ligand coordination geometry about the copper ion. This reflects a suppression of the pseudo-Jahn-Teller distortion that is normally shown by copper(II) compounds with this ligand geometry [Halcrow et al. (2004). New J. Chem. 28, 228-233]. On cooling the compound undergoes an abrupt structural change at 157 +/- 3 K, that does not involve a change in the space group (P1), but causes significant changes to c and the unit-cell angles. This reflects a conformational rearrangement of the complex dication, towards a more typical pseudo-Jahn-Teller elongated coordination geometry. This occurs concurrently with a crystallographic ordering of one of the two perchlorate anions, and a significant displacement of the two lattice acetone molecules. The transformation involves displacements of up to 0.5 A in the non-H atoms of the structure at 30 K, compared with their positions at 300 K. The change in coordination geometry of the complex around 157 K is reflected in a small reduction in its magnetic moment near that temperature. PMID- 20305355 TI - More examples of the 15-crown-5...H2O-M-OH2...15-crown-5 motif, M = Al3+, Cr3+ and Pd2+. AB - Five structures of co-crystals grown from aqueous solutions equimolar in 15-crown 5 (or 15C5) and [M(H(2)O)(6)](NO(3))(n), M = Al(3+), Cr(3+) and Pd(2+), are reported. The hydrogen-bonding patterns in all are similar: metal complexes including the fragment trans-H(2)O-M-OH(2) alternate with 15C5 molecules, to which they are hydrogen bonded, to form stacks. A literature survey shows that this hydrogen-bonding pattern is very common. In each of the two polymorphs of the compound [Al(H(2)O)(6)](NO(3))(3).15C5.4H(2)O there are two independent cations; one forms hydrogen bonds directly to the 15C5 molecules adjacent in the stack, while the other cation is hydrogen-bonded to two water molecules that act as spacers in the stack. These stacks are then crosslinked by hydrogen bonds formed by the three nitrate counterions and the three lattice water molecules. The hydrogen-bonded stacks in [Cr(H(2)O)(5)(NO(3))](NO(3))(2).1.5(15C5).H(2)O are discrete rather than infinite; each unit contains two Cr(3+) complex cations and three 15C5 molecules. These units are again crosslinked by the uncoordinated nitrate ions and a lattice water molecule. In [Pd(H(2)O)(2)(NO(3))(2)].15C5 the infinite stacks are electrically neutral and are not crosslinked. In [Pd(H(2)O)(2)(NO(3))(2)].2(15C5).2H(2)O.2HNO(3) a discrete, uncharged unit containing one Pd complex and two 15C5 molecules is ;capped off' at either end by a lattice water molecule and an included nitric acid molecule. In all five structures the infinite stacks or discrete units form an array that is at least approximately hexagonal. PMID- 20305356 TI - Proton-transfer dynamics in the (HCO3-)2 dimer of KHCO3 from Car-Parrinello and path-integrals molecular dynamics calculations. AB - The proton motion in the (HCO(3)(-))(2) dimer of KHCO(3) at 298 K has been studied with Car-Parrinello molecular dynamics (CPMD) and path-integrals molecular dynamics (PIMD) simulations. According to earlier neutron diffraction studies at 298 K hydrogen is disordered and occupies two positions with an occupancy ratio of 0.804/0.196. A simulation with only one unit cell is not sufficient to reproduce the disorder of the protons found in the experiments. The CPMD results with four cells, 0.783/0.217, are in close agreement with experiment. The motion of the two protons along the O...O bridge is highly correlated inside one dimer, but strongly uncoupled between different dimers. The present results support a mechanism for the disorder which involves proton transfer from donor to acceptor and not orientational disordering of the entire dimer. The question of simultaneous or successive proton transfer in the two hydrogen bonds in the dimer remains unanswered. During the simulation situations with almost simultaneous proton transfer with a time gap of around 1 fs were observed, as well as successive processes where first one proton is transferred and then the second one with a time gap of around 20 fs. The calculated vibrational spectrum is in good agreement with the experimental IR spectrum, but a slightly different assignment of the bands is indicated by the present simulations. PMID- 20305357 TI - Predicted crystal structures of tetramethylsilane and tetramethylgermane and an experimental low-temperature structure of tetramethylsilane. AB - No crystal structure at ambient pressure is known for tetramethylsilane, Si(CH(3))(4), which is used as a standard in NMR spectroscopy. Possible crystal structures were predicted by global lattice-energy minimizations using force field methods. The lowest-energy structure corresponds to the high-pressure room temperature phase (Pa3, Z = 8). Low-temperature crystallization at 100 K resulted in a single crystal, and its crystal structure has been determined. The structure corresponds to the predicted structure with the second lowest energy rank. In X ray powder analyses this is the only observed phase between 80 and 159 K. For tetramethylgermane, Ge(CH(3))(4), no experimental crystal structure is known. Global lattice-energy minimizations resulted in 47 possible crystal structures within an energy range of 5 kJ mol(-1). The lowest-energy structure was found in Pa3, Z = 8. PMID- 20305358 TI - Universal prediction of intramolecular hydrogen bonds in organic crystals. AB - A complete exploration of intramolecular hydrogen bonds (IHBs) has been undertaken using a combination of statistical analyses of the Cambridge Structural Database and computation of ab initio interaction energies for prototypical hydrogen-bonded fragments. Notable correlations have been revealed between computed energies, hydrogen-bond geometries, donor and acceptor chemistry, and frequencies of occurrence. Significantly, we find that 95% of all observed IHBs correspond to the five-, six- or seven-membered rings. Our method to predict a propensity for hydrogen-bond occurrence in a crystal has been adapted for such IHBs, applying topological and chemical descriptors derived from our findings. In contrast to intermolecular hydrogen bonding, it is found that IHBs can be predicted across the complete chemical landscape from a single optimized probability model, which is presented. Predictivity of 85% has been obtained for generic organic structures, which can exceed 90% for discrete classes of IHB. PMID- 20305359 TI - L-2-aminobutyric acid: two fully ordered polymorphs with Z' = 4. AB - The crystal structure of L-2-aminobutyric acid, an L-alanine analogue with an ethyl rather than a methyl side chain, has proved elusive owing to problems growing diffraction quality crystals. Good diffraction data have now been obtained for two polymorphs, in space groups P2(1) and I2, revealing surprisingly complex, yet fully ordered crystalline arrangements with Z' = 4. The closely related structures are divided into hydrophilic and hydrophobic layers, the latter being the thinnest ever found for an amino acid (other than alpha glycine). The hydrophobic layers furthermore contain conspicuous pseudo-centers of-symmetry, leading to overall centrosymmetric intensity statistics. Uniquely, the four molecules in the asymmetric unit can be divided into two pairs that each forms an independent hydrogen-bond network. PMID- 20305360 TI - Precursor effects of the orthorhombic to monoclinic phase transition in benzocaine form (II) revealed by X-ray diffuse scattering. AB - We described the development of a Monte Carlo computer model for the room temperature form (II) polymorph of benzocaine that incorporates, on a local scale, structural features derived from the low-temperature form (III) polymorph. The introduction of this extra information convincingly reproduces those observed diffraction features that an earlier harmonic model was unable to achieve. In both form (I) and form (II) the hydrogen-bonded chains of molecules that extend along the respective a axes tend to slide backward and forward along their lengths. While in form (I) the motion is well modelled by a harmonic potential in form (II) there is a degree of anharmonicity that means that some intermolecular contact vectors, which are identical in the average structure, are distributed bimodally with either longer or shorter vectors being preferred to the average. Moreover there is a tendency for these deviations from average to be correlated to give short-range ordered domains that are the precursors of the two twinned variants of the long-range ordered low-temperature form (III) structure. PMID- 20305362 TI - Obstructive sleep apnea, metabolic syndrome, and age: will geriatricians be caught asleep on the job? AB - Obstructive sleep apnea (OSA) is increasingly recognized in older persons as an important cause of morbidity and mortality, resulting in cardiovascular disease, cognitive dysfunction, and disturbed sleep. It has been cited as an independent risk factor for the metabolic syndrome (MS). The elevated levels of cytokines, such as interleukin-6 and tumor necrosis factor-alpha, which also increase with age, are a common feature of both OSA and MS. Intermittent hypoxia caused by the recurring episodes of apnea and near-apnea in OSA is a major cause of its systemic effects. Mathematical models of OSA show how obesity and anatomic changes in the upper airways, which may be age-related, interact with the networks responsible for the chemical and neural control of breathing to cause the recurrent intermittent hypoxia of sleep apnea. Treatment of OSA with continuous positive airway pressure improves some aspects of the metabolic syndrome, reduces cardiovascular morbidity, and improves domains of cognitive function. OSA is more difficult to identify in the elderly because many of its symptoms can be caused by other disorders which are common in the elderly. Clinicians who encounter OSA may be advised to search for the presence of MS, and vice versa. PMID- 20305363 TI - Quantitative trait loci (QTL) analysis of longevity in C57BL/6J by DBA/2J (BXD) recombinant inbred mice. AB - BACKGROUND AND AIMS: Genes associated with longevity have been identified using both single gene and genome-wide approaches in a variety of species. The aim of this study was to identify quantitative trait loci (QTLs) that influence longevity in male and female mice from twenty-three C57BL/6J by DBA/2J (BXD) recombinant inbred (RI) strains. METHODS: Approximately 12 animals of each sex for each RI strain were maintained under standard conditions until natural death or moribundity criteria were met. RESULTS: A number of life span-relevant loci previously reported on chromosomes (Chrs) 7, 8, 10 and 11 were confirmed. In addition, 5 previously unreported QTLs for mouse life span on Chrs 1, 2, 6, 11, and X were identified as significant and 3 QTLs on Chrs 5, 8, and 16 were suggestive. CONCLUSIONS: Several QTLs were coincident in males and females although the modest correlation between male and female median lifespans and the identification of sex specific QTLs provide evidence that the genetic architecture underlying longevity in the sexes may differ substantially. The identification of multiple QTLs for longevity will provide valuable resources for both reductionist and integrationist research into mechanisms of life span determination. PMID- 20305364 TI - Correlates of D-dimer in older persons. AB - BACKGROUND AND AIMS: D-dimer is a marker of active fibrinolysis. Understanding how age-related factors affect D-dimer levels may help the interpretation of high D-dimer levels in older individuals. METHODS: 776 Baltimore Longitudinal Study on Aging (BLSA) participants (mean age 68.4+/-13.9 yrs) were divided into three groups according to baseline D-dimer levels >200 ng/mL; 100-200 ng/mL and <100 ng/mL. RESULTS: D-dimer level increased with age (p<0.0001). Using polychotomous logistic regression models, we found that age, cholesterol, triglycerides, creatinine, erythrocyte sedimentation rate, hemoglobin and body mass index were independently associated with D-dimer level. CONCLUSIONS: Rising levels of D dimer with age can be explained in part by the high prevalence of pro inflammatory conditions and increasing burden of lipid abnormalities, anemia and obesity. These factors compromise the specificity of D-dimer levels as a diagnostic aid to thrombosis in older individuals. PMID- 20305365 TI - Serum albumin levels as an independent predictor of 4-year mortality in a community-dwelling 80-year-old population. AB - BACKGROUND AND AIMS: Although serum albumin levels are associated with mortality in non-institutionalized elderly people under 80 years old, as well as in the institutionalized very elderly, little is known about the relationship in community-dwelling very elderly people. We, therefore, examined the association in a Japanese population of 80-year-old community residents. METHODS: Serum albumin levels were measured in 672 (267 men, 405 women) out of 1282 80-year-old individuals. Over the following 4 years, the dates and causes of death were recorded from resident registration cards and official death certificates. RESULTS: Of the above individuals, 107 subjects died (58 men, 49 women: 27 due to cancer, 27 cardiovascular disease, and 22 pneumonia). Survival rates were compared among 4 groups (highest >or=45 g/L, higher than 43-44 g/L, lower than 41 42 g/L, lowest 65 years of age with serum 25-hydroxyvitamin D3 (25OHD) concentrations between 20 and 50 nmol/L, visiting an outpatient geriatric department, were included. Participants received either cholecalciferol 400 IU/day + calcium 500 mg/day (D/Cal group) or a placebo + calcium 500 mg/day (Plac/Cal group) for 6 months. At baseline and 6 months, muscle strength, power and functional mobility were tested. RESULTS: At baseline, 25OHD was significantly (p<0.05) associated with knee extension strength (r=0.42), handgrip strength (r=0.28), leg extension power (r=0.34), Timed Get Up and Go (r=-0.31) and Modified Cooper test (r=0.44). At 6 months, a significant difference in 25OHD (77.2 vs 41.6 nmol/L, p<0.001) and 1,25OHD was found between the two groups. Significantly improving vitamin D status in the D/Cal group compared with the Plac/Cal group did not result in a significant difference in strength or functional mobility between the two groups. CONCLUSIONS: Daily 400 IU vitamin D + 500 mg calcium supplementation is not enough to significantly improve strength or mobility in vitamin D-insufficient female geriatric patients. PMID- 20305369 TI - Effects of physical training on aerobic capacity in frail elderly people (75+ years). Influence of lung capacity, cardiovascular disease and medical drug treatment: a randomized controlled pilot trial. AB - BACKGROUND AND AIMS: Frail elderly people often suffer from a combination of unintentional weight loss and/or low body mass index, as well as a low physical activity level. No studies have investigated the effect of physical training alone or in combination with nutritional intervention on aerobic capacity in frail elderly people. The aim of this pilot study was to determine if a physical training program can affect aerobic capacity in frail elderly people. METHODS: Ninety-six community-dwelling frail elderly people (58 women) were included in the study. Subjects were randomized to four different groups: i) physical training program (aerobic, muscle strength, balance), ii) a nutritional intervention program (individually targeted advice and group sessions), iii) a combination of these interventions, and iv) a control group. At baseline, subjects were screened for aerobic capacity, leg muscle strength, spirometry, heart disease and cardiovascular drugs. Aerobic capacity and leg muscle strength were analyzed immediately after the 3-month intervention period (1st follow-up), and after another 6 months (2nd follow-up). RESULTS: Subjects mean age was 83 years. The mean compliance rate with the physical training program was 65%. There were no observed effects on aerobic capacity measured as maximal workload, or work time, with or without beta-receptor blockade. Subjects in the training groups without lung disease significantly increased maximal work time when compared with subjects with lung disease. Physical training significantly increased lower extremity muscle strength compared with nutrition alone at the 1st follow-up. No serious adverse events occurred during assessment or physical training. CONCLUSIONS: Further studies with larger sample sizes and a more specific aerobic component in the training program are necessary before any further conclusions can be drawn. PMID- 20305370 TI - Spontaneous insufficiency fractures of long bones in institutionalized elderly patients. AB - AIM: We report 3 cases of spontaneous insufficiency fracture of long bones, to promote awareness of this phenomenon to medical personnel dealing with long-term bedridden patients. METHODS: Cases were analyzed in the light of a literature review. RESULTS: Our patients were all women, who were severely debilitated and had been bedridden for prolonged periods of time. In all cases, conflicts arose between the patient's family and medical personnel. CONCLUSIONS: Spontaneous insufficiency fractures are rare, and occur mainly in the institutionalized elderly with a prolonged history of immobility. Caregivers should be made aware of this possible complication, as they are aware of bedsores, infections and organ failure, which may arise due to patients' debilitated condition. PMID- 20305371 TI - Stroke recurrence in an elderly CADASIL patient on aspirin discontinuation due to severe auto-immune thrombocytopenia. PMID- 20305372 TI - miR-519 suppresses tumor growth by reducing HuR levels. AB - The RNA-binding protein HuR is highly abundant in many cancers. HuR expression was recently found to be repressed by microRNA miR-519, which potently lowered HuR translation without influencing HuR mRNA abundance. Here, we examined the levels of HuR and miR-519 in pairs of cancer and adjacent healthy tissues from ovary, lung, and kidney. In the three sample collections, the cancer specimens showed dramatically higher HuR levels, unchanged HuR mRNA concentrations, and markedly reduced miR-519 levels, when compared with healthy tissues. As tested using human cervical carcinoma cells, miR-519 reduced tumorigenesis in athymic mice. Compared with the tumors arising from control cells, cells overexpressing miR-519 formed significantly smaller tumors, while cells expressing reduced miR 519 levels gave rise to substantially larger tumors. Evidence that the miR-519 elicited reduction of HuR was critical for its tumor suppressor influence was obtained by reducing HuR, as HuR-silenced cells formed markedly smaller tumors and were unable to form large tumors even after lowering miR-519 abundance. Together, our data reveal that miR-519 inhibits tumorigenesis in large part by repressing HuR expression. PMID- 20305374 TI - Novel combination of celecoxib and proteasome inhibitor MG132 provides synergistic antiproliferative and proapoptotic effects in human liver tumor cells. AB - Molecular targeted therapy has shown promise as a treatment for advanced hepatocellular carcinoma (HCC). Celecoxib (Celebrex(r)) exhibits antitumor effects in human HCC cells, and its mechanism of action is mediated either by its ability to inhibit cyclooxygenase 2 (COX-2) or by a number of various other COX-2 independent effects. Proteasome inhibitors (PIs) can exert cell growth inhibitory and apoptotic effects in different tumor cell types, including HCC cells. The present study examined the interaction between celecoxib and the PI MG132 in two human liver tumor cell lines HepG2 and HA22T/VGH. Our data showed that each inhibitor reduced proliferation and induced apoptosis in a dose-dependent manner in both cell lines. Moreover, the combination of celecoxib with MG132 synergistically inhibited cell viability and increased apoptosis, as documented by caspase 3 and 7 activation, PARP cleavage, and down-regulation of Bcl-2. Celecoxib and MG132, both alone and synergistically in combination, induced expression of the endoplasmic reticulum (ER) stress genes ATF4, CHOP, TRB3 and promoted the splicing of XBP1 mRNA. Knockdown of TRB3 mRNA expression by small interference RNA significantly decreased combination-induced cell death in HA22T/VGH cells, whereas it increased combination-induced cell death in HepG2 cells, suggesting that activation of the ER stress response might have either a detrimental or a protective role in liver tumor cell survival. In conclusion, our data indicate that combination treatment with celecoxib and MG132 resulted in synergistic antiproliferative and proapoptotic effects against liver cancer cells, providing a rational basis for the clinical use of this combination in the treatment of liver cancer. PMID- 20305373 TI - Repetitive element DNA methylation and circulating endothelial and inflammation markers in the VA normative aging study. AB - BACKGROUND: Lower blood DNA methylation has been associated with atherosclerosis and high cardiovascular risk. Mechanisms linking DNA hypomethylation to increased cardiovascular risk are still largely unknown. In a population of community dwelling elderly individuals, we evaluated whether DNA methylation in LINE-1 repetitive element, heavily methylated sequences dispersed throughout the human genome, was associated with circulating Vascular Cell Adhesion Molecule-1 (VCAM 1), Inter- Cellular Adhesion Molecule-1 (ICAM-1), and C-reactive protein (CRP). METHODS AND RESULTS: We measured LINE-1 methylation by bisulfite PCR Pyrosequencing on 742 blood DNA samples from male participants in the Boston area Normative Aging Study (mean age=74.8 years). Mean serum VCAM-1 increased progressively in association with LINE-1 hypomethylation (from 975.2 to 1063.4 ng/ml in the highest vs. lowest methylation quintiles; ptrend= 0.004). The association between VCAM-1 and LINE-1 hypomethylation was significant in individuals without ischemic heart disease or stroke (n=480; p=0.001), but not in those with prevalent disease (n=262; p=0.57). Serum ICAM-1 and CRP were not associated with LINE-1 methylation (p-trend=> 0.25). All results were confirmed by multivariable analyses adjusting for age, BMI, smoking, pack-years, and ischemic heart disease/stroke. CONCLUSIONS: LINE-1 element hypomethylation is associated with higher serum VCAM-1. Our data provide new insights into epigenetic events that may accompany the development of cardiovascular disease. PMID- 20305375 TI - P-TEFb stimulates transcription elongation and pre-mRNA splicing through multilateral mechanisms. AB - Promoter-proximal pausing of RNA polymerase II (RNAPII) across the genome has renewed our attention to the early transcriptional events that control the establishment of pausing and the release of RNAPII into a productive transcription elongation. Here, we review our current understanding of the transcriptional cycle by RNAPII with a particular emphasis on the mechanisms that stimulate transcription elongation and cotranscriptional pre-mRNA splicing through an essential transcriptional kinase, the positive transcription elongation factor b (P-TEFb). We illustrate that by targeting a limited set of transcription elongation factors and paused RNAPII molecule during a promoter proximal phase of transcription, P-TEFb unleashes an extensive crosstalk between transcription apparatus, RNA processing factors and chromatin for optimal production of mRNA. PMID- 20305376 TI - Viruses and the autophagy machinery. AB - Autophagy is a major intracellular pathway for degradation and recycling of long lived proteins and cytoplasmic organelles that plays an essential role in maintenance of homeostasis in response to starvation and other cellular stresses. Autophagy is also important for a variety of other processes including restriction of intracellular pathogen replication. Our understanding of the fascinating relationship between viruses and the autophagy machinery is still in its infancy but it is clear that autophagy is a newly recognized facet of innate and adaptive immunity against viral infection. Although the autophagy pathway is emerging as a component of host defense, certain viruses have developed strategies to counteract these antiviral mechanisms, and others appear to have co opted the autophagy machinery as proviral host factors favoring viral replication. The complex interplay between autophagy and viral infection will be discussed in this review. PMID- 20305377 TI - Metformin and cancer: doses, mechanisms and the dandelion and hormetic phenomena. AB - In the early 1970s, Professor Vladimir Dilman originally developed the idea that antidiabetic biguanides may be promising as geroprotectors and anticancer drugs ("metabolic rehabilitation"). In the early 2000s, Anisimov's experiments revealed that chronic treatment of female transgenic HER2-/neu mice with metformin significantly reduced the incidence and size of mammary adenocarcinomas and increased the mean latency of the tumors. Epidemiological studies have confirmed that metformin, but not other anti-diabetic drugs, significantly reduces cancer incidence and improves cancer patients' survival in type 2 diabetics. At present, pioneer work by Dilman & Anisimov at the Petrov Institute of Oncology (St. Petersburg, Russia) is rapidly evolving due to ever-growing preclinical studies using human tumor-derived cultured cancer cells and animal models. We herein critically review how the antidiabetic drug metformin is getting reset to metabolically fight cancer. Our current perception is that metformin may constitute a novel "hybrid anti-cancer pill" physically combining both the long-lasting effects of antibodies -by persistently lowering levels of blood insulin and glucose- and the immediate potency of a cancer cell-targeting molecular agent -by suppressing the pivotal AMPK/mTOR/S6K1 axis and several protein kinases at once, including tyrosine kinase receptors such as HER1 and HER2-. In this scenario, we discuss the relevance of metformin doses in pre clinical models regarding metformin's mechanisms of action in clinical settings. We examine recent landmark studies demonstrating metformin's ability to specifically target the cancer-initiating stem cells from which tumor cells develop, thereby preventing cancer relapse when used in combination with cytotoxic chemotherapy (dandelion hypothesis). We present the notion that, by acting as an efficient caloric restriction mimetic, metformin enhanced intrinsic capacity of mitotically competent cells to self-maintenance and repair (hormesis) might trigger counterintuitive detrimental effects. Ongoing chemopreventive, neoadjuvant and adjuvant trials should definitely establish whether metformin's ability to kill the "dandelion root" beneath the "cancer soil" likely exceeds metformin-related dangers of hormesis. PMID- 20305378 TI - Inactivation of p53 signaling by p73 or PTEN ablation results in a transformed phenotype that remains susceptible to Nutlin-3 mediated apoptosis. AB - The p53 signaling pathway is frequently disrupted in carcinogenesis. However, roughly 50% of all cancers express wild-type p53 and have alterations in accessory signaling components required for p53 activity. Using the well described E1A/RAS transformation model, in which p53 activity must be suppressed for transformation, we show here that p53 is inactive and unable to suppress transformation following ablation of p73 or PTEN. However, despite the transformed phenotype conferred by p53 inactivation following p73 or PTEN loss, p53 could be fully activated by Nutlin-3, resulting in efficient caspase-mediated apoptosis. Our novel and unexpected finding provides important information regarding the efficacy of Nutlin-3 and indicates that patients with tumors deficient in p53 function due to p73 or PTEN loss may benefit from Nutlin-3 treatment. PMID- 20305379 TI - Sub1/PC4 a chromatin associated protein with multiple functions in transcription. AB - Yeast Sub1 and its human ortholog PC4 display multiple cellular functions in vivo. Sub1/PC4 contains a unique conserved non-specific DNA-binding domain and is involved in distinct DNA-dependent processes including replication, DNA repair and transcription. Sub1/PC4 is a non-histone chromatin-associated protein initially described as a co-activator for RNA polymerase (Pol) II transcription in vitro. Recently, biochemical and genomic studies showed that Sub1 is not restricted to Pol II transcription but is also involved in Pol III transcription revealing a more general role in transcription than anticipated. Sub1/PC4 appears to play a dual (positive and negative) complex role in gene expression and has multiple effects in distinct steps of the transcription cycle, consisting of initiation, elongation, termination and reinitiation. Here, the multiple transcriptional functions of Sub1/PC4 will be reviewed and the recent findings and their possible implications in the understanding of Sub1/PC4 function in transcription will be discussed. PMID- 20305380 TI - Tropomyosin isoform modulation of focal adhesion structure and cell migration. AB - Orderly cell migration is essential for embryonic development, efficient wound healing and a functioning immune system and the dysregulation of this process leads to a number of pathologies. The speed and direction of cell migration is critically dependent on the structural organization of focal adhesions in the cell. While it is well established that contractile forces derived from the acto myosin filaments control the structure and growth of focal adhesions, how this may be modulated to give different outcomes for speed and persistence is not well understood. The tropomyosin family of actin-associating proteins are emerging as important modulators of the contractile nature of associated actin filaments. The multiple non-muscle tropomyosin isoforms are differentially expressed between tissues and across development and are thought to be major regulators of actin filament functional specialization. In the present study we have investigated the effects of two splice variant isoforms from the same alpha-tropomyosin gene, TmBr1 and TmBr3, on focal adhesion structure and parameters of cell migration. These isoforms are normally switched on in neuronal cells during differentiation and we find that exogenous expression of the two isoforms in undifferentiated neuronal cells has discrete effects on cell migration parameters. While both isoforms cause reduced focal adhesion size and cell migration speed, they differentially effect actin filament phenotypes and migration persistence. Our data suggests that differential expression of tropomyosin isoforms may coordinate acto-myosin contractility and focal adhesion structure to modulate cell speed and persistence. PMID- 20305381 TI - DNA hypomethylation in cancer: epigenetic scars of a neoplastic journey. AB - Cytosine methylation is a heritable modification of DNA in mammalian cells, and has a determinant impact on long-term gene repression and genome stability. Genomic methylation patterns, which remain generally stable in the adult, become profoundly altered in most human tumors. While discrete DNA segments become hypermethylated in cancer cells, many more sequences become hypomethylated. This review discusses our current understanding of the mechanisms that lead to DNA hypomethylation in tumors. Evidence suggests that methylation losses are not random, but rather evolve into mosaic hypomethylation patterns. It is proposed that such hypomethylation patterns result from a historical event of transient DNA demethylation, and that transcriptional regulators contribute to determining which regions escape remethylation and remain therefore unmethylated. Finally, possible stages of tumor development during which the transient DNA demethylation process may take place will be discussed. PMID- 20305383 TI - New perspectives for the regulation of acetyltransferase MOF. AB - In higher eukaryotes, histone acetyltransferase MOF (male absent on the first) is the major enzyme that acetylates histone H4 lysine 16, a prevalent mark associated with chromatin decondensation. Recent studies show that MOF resides in two different but evolutionarily conserved complexes, MSL and MOF-MSL1v1. Although these two MOF complexes have indistinguishable activity on histone H4 K16, they differ dramatically in acetylating non-histone substrate p53. The regulation of MOF activity in these complexes remains elusive. Given the evolution conservation of MOF and the importance of H4 K16 acetylation in maintaining higher order chromatin structures, understanding the function and regulation of MOF bears great significance. Here, we discussed the key differences in two MOF complexes that may shed light on the regulation of their distinct acetyltransferase activities. We also discussed coordinated functions of two MOF complexes with different histone methyltransferase complexes in transcription regulation. PMID- 20305384 TI - 5-azacytidine treatment reorganizes genomic histone modification patterns. AB - Methylation of DNA in combination with histone modifications establishes an epigenetic code that ensures the proper control of gene expression. Although DNA methyltransferases have been shown to interact with histone methyltransferases such as EZH2 (which methylates histone H3 on lysine 27) and G9a (which methylates histone H3 on lysine 9), the relationship between DNA methylation and repressive histone marks has not been fully studied. In cancer cells, promoters of genes are often aberrantly methylated. Accordingly, 5-azacytidine (a DNA demethylating drug) is used for treating patients with myelodysplastic syndrome. However, no genome-scale studies of the effects of this drug have been reported. In this work, we report the effects of 5-azacytidine on global gene expression and analyze ~24,000 human promoters using ChIP-chip to determine how 5-azacytidine treatment effects H3K27me3 and H3K9me3 levels. We found that (1) 5-azacytidine treatment results in large changes in gene regulation with distinct functional categories of genes showing increased (e.g. C2H2 zinc finger transcription factors) and decreased (e.g. genes involved in regulation of mitochondria and oxidoreductase activity) levels; (2) most genes that show altered expression are not regulated by promoters that display DNA methylation prior to the treatment; (3) certain gene classes switch their repression mark upon treatment with 5 azacytidine (from H3K27me3 to H3K9me3 and vice versa); and (4) most changes in gene expression are not due to relief of repression mediated by DNA or histone methylation. PMID- 20305382 TI - The fast and slow ups and downs of HCN channel regulation. AB - Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels (h channels) form the molecular basis for the hyperpolarization-activated current, I(h), and modulation of h channels contributes to changes in cellular properties critical for normal functions in the mammalian brain and heart. Numerous mechanisms underlie h channel modulation during both physiological and pathological conditions, leading to distinct changes in gating, kinetics, surface expression, channel conductance or subunit composition of h channels. Here we provide a focused review examining mechanisms of h channel regulation, with an emphasis on recent findings regarding interacting proteins such as TRIP8b. This review is intended to serve as a comprehensive resource for physiologists to provide potential molecular mechanisms underlying functionally important changes in I(h) in different biological models, as well as for molecular biologists to delineate the predicted h channel changes associated with complex regulatory mechanisms in both normal function and in disease states. PMID- 20305385 TI - Kinesin-5 mitotic motors: Is loop5 the on/off switch? AB - The microtubule-based mitotic spindle orchestrates chromosome segregation, facilitated by many microtubule-associated proteins. Kinesin-5 proteins are important components of the cell division machinery, and are involved in generation of mitotic spindle bipolarity by cross-linking microtubules. Kinesin 5s are members of the ATP- and MT-dependent kinesin superfamily of molecular motors. Human kinesin-5 is also a target for small molecule inhibitors that specifically bind to the motor domain and are currently in cancer clinical trials. The regulatory mechanisms that control kinesin-5 activity during mitosis and the effects of regulation on the kinesin-5-microtubule interaction remain unknown. Recent work has focused on a kinesin-5 specific region within the motor domain, loop5, as a potential regulatory switch. Kinesin-5-specific small molecule inhibitors bind beneath loop5, loop5 is rearranged when kinesin-5 binds to microtubules and residues adjacent to loop5 are subject to cell cycle dependent tyrosine phosphorylation which could affect its conformation. It will be essential to consider these studies, which shed light on potential kinesin-5 regulatory mechanisms, as part of efforts to develop clinically effective kinesin 5 inhibitors. PMID- 20305386 TI - C/EBPalpha enters the nucleolus. PMID- 20305387 TI - Netrin-1, a missing link between chronic inflammation and tumor progression. AB - Netrin-1 discovered as a neuronal navigation cue, has been recently proposed to play a crucial role during colorectal tumorigenesis by regulating apoptosis. This survival activity is mediated via the inhibition of the so-called netrin-1 dependence receptors. The netrin-1 receptors, DCC (for Deleted in Colorectal Cancer) and UNC5H (UNC5 homologues), indeed belong to the functional family of dependence receptors that share the ability to induce apoptosis in the absence of their ligands and such a trait has been hypothesized to confer these receptors a tumor suppressor activity as their presence render cell survival dependent on ligand availability. As a consequence, human tumors show either a loss of dependence receptors or a gain of netrin-1, allowing tumors to escape this safeguard mechanism. We recently found that netrin-1 is a direct transcriptional target of the transcription factor NFkappaB, and that a fraction of colorectal tumors show a netrin-1 gain parallel to NFkappaB activation. Moreover, colorectal cancers from patients affected by inflammatory bowel diseases (IBD) show upregulation of netrin-1. Several evidences suggest a tight link between chronic inflammation and tumorigenesis, mainly through NFkappaB activation. We propose that induction of netrin-1 expression via NFkappaB in IBD patients could affect colorectal tumor promotion and progression and that inhibition of netrin-1 could be an innovative target for drug therapy in inflammation-driven colorectal cancers. PMID- 20305388 TI - Cardiac desmosomal (dys)function and myocyte viability. AB - Cardiac desmosomes form intercellular junctions at the boundaries of intercalated discs between neighboring cardiomyocytes and are essential for proper cell-to cell coupling between cardiomyocytes and for normal mechanical and electrical function of myocardial tissue. Genetic mutations in desmosomal proteins have been associated with arrhythmogenic right ventricular cardiomyopathy (ARVC), a clinically and genetically heterogeneous cardiac inherited disorder. The disease is characterized by progressive replacement of cardiomyocytes by fibrofatty tissue, ultimately resulting in ventricular dilation, cardiac dysfunction, and the occurrence of life-threatening arrhythmias. Despite increasing knowledge on the genetic basis of ARVC, the etiopathogenesis of the disease remains less understood. The recent development of a number of transgenic mouse models with either heterozygous knock-out of desmosomal proteins or overexpression of aberrant desmosomal components has provided novel insight into the potential mechanisms and final common pathways involved in ARVC. The various disease mechanisms are likely not mutually exclusive and may each contribute to the pathogenesis of ARVC. However, their applicability in the diverse genetic forms of the disease remains uncertain, and may only be ascertained by careful investigation of sequential histopathological and (sub)cellular changes occurring over time during the disease process. Insight into the etiopathogenesis of ARVC will be crucial for the future development of new therapies aimed at delaying onset or progression of this disease. PMID- 20305389 TI - Nucleolar organization, growth control and cancer. AB - The nucleolus is a dynamic region of the nucleus that is disassembled and reformed each cell cycle and whose size is correlated with cell growth rate. Nucleolar size is a prognostic measure of cancer disease severity and increasing evidence suggests a causative role of nucleolar lesions in many cancers. In recent work (Shiue et al. Oncogene 28, 1833-42, 2009) we showed that the c-Myc oncoprotein induces changes in the higher order structure of rDNA chromatin in the nucleolus of growth stimulated quiescent rat cells. Here we show that c-Myc induces similar changes in human cells, that c-Myc plays a role in the overall structural integrity of the nucleolus and that c-Myc and its antagonistic partner Mad1 interact to program the epigenetic status of rDNA chromatin. These changes are discussed in relation to current knowledge about nucleolar structure as well as the organization of chromosomes and transcription factories in nuclear regions outside the nucleolus. PMID- 20305390 TI - Autophagy by hepatitis B virus and for hepatitis B virus. AB - Autophagy is a catabolic process by which cells remove unwanted proteins and damaged organelles. It is important for maintaining cellular homeostasis and can also be used by cells to remove intracellular microbial pathogens. As such, some viruses such as herpes simplex virus-1 (HSV-1) have evolved mechanisms to suppress autophagy for their survival. In contrast, other viruses such as poliovirus, hepatitis C virus (HCV) and dengue viruses have instead evolved mechanisms to use this pathway to enhance their replication. Recently, we demonstrated that hepatitis B virus (HBV), a DNA virus that infects hepatocytes, could enhance and use autophagy for its DNA replication. This enhancement of autophagy is mediated by its X protein, which binds to and activates phosphatidylinositol-3-kinase class 3 (PI3KC3), an enzyme important for the initiation of autophagy. The persistent activation of autophagy in hepatocytes by HBV during chronic infection may play an important role in HBV pathogenesis. PMID- 20305391 TI - From chromatin to splicing: RNA-processing as a total artwork. AB - RNA plays a central role in the determination of the phenotype of the cell. The molecular mechanisms involved in primary RNA synthesis and subsequent post processing are not completely understood, but there is increasing evidence that they are more tightly coupled than previously expected. The analyses by a number of groups of recently published genome wide maps of chromatin structure have further uncovered a role for primary chromatin structure in RNA processing. Indeed, these analyses have revealed that nucleosomes show a characteristic occupancy pattern in exonic regions of metazoan genomes. The pattern is strongly indicative of an implication of nucleosome positioning in exon recognition during pre-mRNA splicing. Characteristic exonic patterns have also been observed for a number of histone modifications, suggesting the possibility that chromatin state plays a direct role in the regulation of splicing. PMID- 20305392 TI - A karyopherin acts in localized protein synthesis. AB - Multiple mechanisms are in place to regulate adequate synthesis of proteins, ranging from ways to ensure sequence fidelity, polypeptide folding and protein modification, to control of amounts and subcellular localization of the molecules. Some of these mechanisms act at the level of mRNA export and mRNA targeting. mRNA nuclear export consists of three coupled consecutive steps: (1) the packaging into messenger ribonucleoprotein (mRNP); (2) the transport through the nuclear pore complexes (NPCs); and (3) the directional release into the cytoplasm (reviewed in refs. 1 and 2). The subsequent targeting of mRNA to particular subcellular locations is common in asymmetric cell division in many eukaryotes (reviewed in refs. 3-5) and ensures that proteins are produced at the desired place. Recent studies in Saccharomyces cerevisiae suggest that Karyopherin Kap104p plays a role not only in mRNA export but also in bud localized protein synthesis. In this report, we reflect on the possible mechanisms by which Kap104p links these events and hypothesize on a possible function of the localized protein synthesis. PMID- 20305393 TI - Identification of Filamin A as a BRCA1-interacting protein required for efficient DNA repair. AB - The product of the breast and ovarian cancer susceptibility gene BRCA1 has been implicated in several aspects of the DNA damage response but its biochemical function in these processes has remained elusive. In order to probe BRCA1 function we conducted a yeast two-hybrid screening to identify interacting partners to a conserved motif (Motif 6) in the central region of BRCA1. Here we report the identification of the actin-binding protein Filamin A (FLNA) as BRCA1 partner and demonstrate that FLNA is required for efficient regulation of early stages of DNA repair processes. Cells lacking FLNA display a diminished BRCA1 IR induced focus formation and a delayed kinetics of Rad51 focus formation. In addition, our data also demonstrate that FLNA is required to stabilize the interaction between components of the DNA-PK holoenzyme, DNA-PKcs and Ku86 in a BRCA1-independent fashion. Our data is consistent with a model in which absence of FLNA compromises homologous recombination and non-homologous end joining. Our findings have implications for the response to irradiation induced DNA damage. PMID- 20305394 TI - Fibril fragmentation in amyloid assembly and cytotoxicity: when size matters. AB - Amyloid assemblies are associated with several debilitating human disorders. Understanding the intra- and extracellular assembly of normally soluble proteins and peptides into amyloid aggregates and how they disrupt normal cellular functions is therefore of paramount importance. In a recent report, we demonstrated a striking relationship between reduced fibril length caused by fibril fragmentation and enhanced ability of fibril samples to disrupt membranes and to reduce cell viability. These findings have important implications for our understanding of amyloid disease in that changes in the physical dimensions of fibrils, without parallel changes in their composition or molecular architecture, could be sufficient to alter the biological responses to their presence. These conclusions provide a new hypothesis that the physical dimensions and surface interactions of fibrils play key roles in amyloid disease. Controlling fibril length and stability toward fracturing, and thereby the biological availability of fibril material, may provide a new target for future therapeutic strategies towards combating amyloid disease. PMID- 20305395 TI - Potent and broad neutralizing activity of a single chain antibody fragment against cell-free and cell-associated HIV-1. AB - Several human monoclonal antibodies (hmAbs) exhibit relatively potent and broad neutralizing activity against HIV-1, but there has not been much success in using them as potential therapeutics. We have previously hypothesized and demonstrated that small engineered antibodies can target highly conserved epitopes that are not accessible by full-size antibodies. However, their potency has not been comparatively evaluated with known HIV-1-neutralizing hmAbs against large panels of primary isolates. We report here the inhibitory activity of an engineered single chain antibody fragment (scFv), m9, against several panels of primary HIV 1 isolates from group M (clades A-G) using cell-free and cell-associated virus in cell line-based assays. M9 was much more potent than scFv 17b, and more potent than or comparable to the best-characterized broadly neutralizing hmAbs IgG(1) b12, 2G12, 2F5 and 4E10. It also inhibited cell-to-cell transmission of HIV-1 with higher potency than enfuvirtide (T-20, Fuzeon). M9 competed with a sulfated CCR5 N-terminal peptide for binding to gp120-CD4 complex, suggesting an overlapping epitope with the coreceptor binding site. M9 did not react with phosphatidylserine (PS) and cardiolipin (CL), nor did it react with a panel of autoantigens in an antinuclear autoantibody (ANA) assay. We further found that escape mutants resistant to m9 did not emerge in an immune selection assay. These results suggest that m9 is a novel anti-HIV-1 candidate with potential therapeutic or prophylactic properties, and its epitope is a new target for drug or vaccine development. PMID- 20305397 TI - Hyperglycemia and acute coronary syndrome: a systematic review of hyperglycemia's impact on ACS. AB - The association between hyperglycemia and increased mortality associated with acute coronary syndrome (ACS) has been studied and affirmed. Although more studies are needed to explore how managing this hyperglycemia can affect ACS mortality, the need to educate regarding current data is urgent so that it can be clinically applied. Reviews, randomized controlled trials, and other studies were obtained by means of electronic search strategies, such as Medline and Cochrane Library, as well as hand selection. Sources selected were limited to those that discussed ACS and hyperglycemia, and specific emphasis was placed on sources that focused on ACS and hyperglycemia in conjunction with one another. Selected studies were then assessed for quality and relevance. Clear correlations between mean and persistent glucose levels and ACS mortality are found. Persistent glucose levels offer a better model to predict ACS mortality than on-admission glucose levels. However, findings concerning the effect on ACS-related mortality of controlling glucose levels have been conflicting. PMID- 20305396 TI - Tuning the chemosensory window: a fly's perspective. AB - Accurate perception of chemical signals from the environment is critical for the fitness of most animals. Drosophila melanogaster experiences its chemical environment through families of chemoreceptors that include olfactory receptors, gustatory receptors and odorant binding proteins. Its chemical environment, however, changes during its life cycle and the interpretation of chemical signals is dependent on dynamic social and physical surroundings. Phenotypic plasticity of gene expression of the chemoreceptor repertoire allows flies to adjust the chemosensory window through which they "view" their world and to modify the ensemble of expressed chemoreceptor proteins in line with their developmental and physiological state and according to their needs to locate food and oviposition sites under different social and physical environmental conditions. Furthermore, males and females differ in their expression profiles of chemoreceptor genes. Thus, each sex experiences its chemical environment via combinatorial activation of distinct chemoreceptor ensembles. The remarkable phenotypic plasticity of the chemoreceptor repertoire raises several fundamental questions. What are the mechanisms that translate environmental cues into regulation of chemoreceptor gene expression? How are gustatory and olfactory cues integrated perceptually? What is the relationship between ensembles of odorant binding proteins and odorant receptors? And, what is the significance of co-regulated chemoreceptor transcriptional networks? PMID- 20305398 TI - Is the device development process adequate. PMID- 20305399 TI - The in vitro effects of Xancor, a synthetic astaxanthine derivative, on hemostatic biomarkers in aspirin-naive and aspirin-treated subjects with multiple risk factors for vascular disease. AB - Astaxanthine is a polar carotenoid metabolite derived from a proprietary prodrug, Xancor, which aligns parallel with the membrane phospholipids exhibiting potent antioxidant, anti-inflammatory, and cell protective properties, although the precise mechanism of action is unknown. This prodrug is currently under development for hepatic, neurologic, and vascular disease indications. Considering established links between heart disease and stroke with platelets, coagulation cascade, and fibrinolysis, the aim of the study was to assess the effect of asthaxantine on human biomarkers of hemostasis. The rationale was to test a hypothesis that the drug may diminish activation of hemostasis, making it a potentially attractive addition to treat patients with vascular disease. In vitro effects of whole blood preincubation with escalating concentrations of asthaxantine (0.3 microM, 1 microM, 3 microM, 10 microM, 30 microM, and 100 microM) were assessed from 12 aspirin-naive and eight aspirin-treated volunteers with multiple risk factors for vascular disease. A total of 25 biomarkers were measured, of which 12 were related to platelet function, 10 to coagulation, and three to fibrinolysis. Platelet aggregation induced by ADP, collagen, and arachidonic acid and expression of CD31, CD41, GP IIb/IIIa, CD51/61, P-selectin, CD63, CD107a, CD151+CD14, and CD154 were not affected. Coagulation indices such as aPTT, prothrombin time, thrombin time, fibrinogen, antithrombin III (antigen and activity), Protein C, Protein S (free and activity), and von Willebrand factor remained unchanged after incubation with astaxanthine. Fibrinolytic activity biomarkers such as plasminogen, D-dimer, and FDP were also not affected after in vitro pretreatment of blood samples with astaxanthine. In the projected subclinical (less than 1 microM), therapeutic (3 microM to 30 microM), and supratherapeutic concentration (100 microM), astaxanthine in vitro does not affect platelet, coagulation, or fibrinolytic indices in either aspirin-naive or aspirin-treated subjects. These results are important for the assessment of the safety profile, but remain to be confirmed preclinically, in vivo, and ultimately in the clinic. PMID- 20305400 TI - Newer therapies for osteoporosis. AB - The existing drugs for treatment of osteoporosis are limited in scope, tolerability, and efficacy. Newer osteoclast-targeted agents like inhibitors of receptor activator nuclear factor kappaB pathway, Cathepsin K, and integrins are under clinical development. Osteoblast-targeted therapies include the agents acting through the Wnt signaling pathway like sclerostin antagonists. The potential molecular targets and the emerging drugs for treatment of osteoporosis are discussed in this review. PMID- 20305401 TI - Have clinical studies demonstrated diabetes prevention or delay of diabetes through early treatment? AB - The incidence of type 2 diabetes continues to increase at alarming rates. Prediabetes is a state of abnormal glycemic values that are not abnormal enough to result in the diagnosis of type 2 diabetes. Significant interest in the prevention of diabetes has resulted in trials evaluating pharmacologic intervention and lifestyle intervention to prevent the development of diabetes. Controversy exists over the exact definition of diabetes prevention. Agents might possibly delay diagnosis of diabetes via pharmacologic lowering of blood glucose. Goals of diabetes prevention include decreased cardiovascular disease. Trials assessing diabetes prevention should assess 1) Impact of the study drug upon the incidence of diabetes, 2) Impact of the study drug upon diagnosis of diabetes after post-treatment washout phase, 3) Assessment of insulin sensitivity/@-cell function/insulin secretion and blood glucose, 4) Assessment of confounding factors, 5) Impact of the study drug on the occurrence of cardiovascular disease. The published studies were reviewed using these criteria. Six studies evaluating seven agents have been were reviewed. Six of the seven agents reduced diagnosis of diabetes during use, but only two demonstrated effect after washout phase. One of the two agents has been withdrawn from the market. The second agent had a short follow-up period making the results difficult to interpret. Assessment of insulin secretion at entry to trial was common, however ongoing reassessment was uncommon. All studies attempted to assess confounding factors, however stratification of drug benefit relative to amount of lifestyle modification benefit was not reported in trials. Cardiovascular benefit in the form of reduced hypertension was documented with three agents. Pharmacologic prevention of type 2 diabetes remains unproven, due in part to the difficulty distinguishing between prevention and delay. Reduction in cardiovascular benefit is unproven with most agents studied. Larger studies powered to detect cardiovascular endpoints are necessary to determine benefit of diabetes prevention. PMID- 20305402 TI - Chloroform anesthesia and the Saville Kent murder in 1860. AB - The discovery of the anesthetic properties of chloroform by Sir James Simpson is one of the therapeutic triumphs of the 19th century. Queen Victoria requested chloroform anesthesia for the birth of her second son, Prince Leopold, and from then until the end of century chloroform was the most popular general anesthetic for obstetrics and surgery. Chloroform was so pleasant to inhale that it became a drug of abuse and was involved in all sorts of criminal activity. Despite its wide usage, chloroform was not thought to be part of the brutal murder of 3-year old Saville Kent on the night of June 30, 1860, outside his manor house in southwest England. The events surrounding and after the murder have recently been documented by Kate Summerscale in a book entitled, "The Suspicions of Mr. Whicher," the Detective Inspector assigned to the case by Scotland Yard. According to Ms Summerscale's records, Mr Whicher ignored the possibility that chloroform was involved in Saville's death. However, evidence supports the view that chloroform played a critical role in the crime and indicates that the guilty plea by Samuel Kent's daughter, Constance, for which she spent 20 years to the day in prison, was as inaccurate as it was incomplete. PMID- 20305407 TI - Tc-99m sestamibi thyroid imaging in patients on chronic amiodarone treatment: a comparison with Tc-99m pertechnetate imaging. AB - PURPOSE OF THE REPORT: To compare thyroid imaging using Tc-99m sestamibi with the standard Tc-99m pertechnetate scintigraphy in patients on chronic use of amiodarone. MATERIALS AND METHODS: A total of 23 patients on oral amiodarone for at least 4 months had thyroid scintigraphy and uptake measurement using Tc-99m pertechnetate and Tc-99m sestamibi. Thyroid function was evaluated by measuring serum concentrations of thyrotropin, free thyroxine, and free triiodothyronine, and antithyroglobulin and antithyroperoxidase antibodies. RESULTS: Ten of the 23 patients were euthyroid, 9 hypothyroid, and 4 hyperthyroid, with normal, increased, and decreased serum thyrotropin, respectively. All euthyroid patients had markedly decreased thyroid Tc-99m pertechnetate uptake and normal or slightly increased Tc-99m sestamibi uptake, except for one patient who had increased uptake of both radiotracers. One of the 4 hyperthyroid patients had Graves' disease and markedly increased thyroid uptake of both tracers. The other 3 hyperthyroid patients had normal or decreased Tc-99m pertechnetate uptake and increased Tc-99m sestamibi uptake. Differently than expected, all 9 hypothyroid patients had normal or increased uptake of both radiopharmaceuticals. CONCLUSIONS: This study suggests that Tc-99m sestamibi may be an alternative tracer for thyroid scintigraphy and uptake measurement of patients on chronic use of amiodarone. Tc-99m sestamibi seems to be better than Tc-99m pertechnetate for the scintigraphic evaluation of the thyroid of euthyroid and hyperthyroid patients. PMID- 20305409 TI - The role of bone SPECT/CT in the evaluation of lumbar spinal fusion with metallic fixation devices. AB - PURPOSE: It is difficult to evaluate the stability of the lumbar spondylodesis with metallic fixation devices by conventional imaging methods such as radiography or magnetic resonance imaging. It is unknown whether single photon emission computed tomography/computed tomography (SPECT/CT) may be useful to detect a lack of fixation of the pedicle screws and hence to predict instability of the fused vertebral segments. MATERIALS AND METHODS: A retrospective analysis of 9 patients who were referred to bone scintigraphy, including combined SPECT/CT, due to persistent pain or discomfort after stabilizing lumbar surgery with metallic implants. The SPECT/CT findings were compared with observations from subsequent surgical reexploration. RESULTS: In 6 of 9 patients, the SPECT/CT fully or partially detected the vertebral level of loose pedicle screws. Of 9 cases, 2 were considered inconclusive, whereas in 1 case loose pedicle screws were detected at a wrong vertebral level. CONCLUSION: SPECT/CT may be useful to detect a lack of fixation of the metallic implants, and hence instability of the spondylodesis by evaluating the focal bone mineralization activity in relation to the pedicle screws. PMID- 20305408 TI - Cortical and subcortical patterns of I-123 iodobenzamide SPECT in striatal D(2) receptor parkinsonisms. AB - INTRODUCTION: The D(2) receptor is the most widely expressed dopaminergic receptor in the central nervous system, and it is present at the pre- and postsynaptic dopaminergic regions. It is mainly located in the neostriatum as well as in the globus pallidus, substantia nigra, cerebral cortex, thalamus, etc. The objective of this study was to analyze qualitatively and quantitatively the distribution pattern of the postsynaptic dopamine receptors through SPECT with iodobenzamide (IBZM) in patients with parkinsonism and to determine the benefit of this imaging technique in the differential diagnosis of the parkinsonian syndromes. MATERIALS: A total of 26 patients with clinical and imaging (Iodine 123 fluoropropyl-carbomethoxy-3 beta-(4-iodophenyltropane) [FP-CIT]) diagnostics of parkinsonism, to all of which a study of postsynaptic D(2) receptors with IBZM was made, were retrospectively reviewed. Of total, 12 patients were male (42.85%). The average age was 73 years old (range, 64-83 years). The patients were imaged using SPECT 2 hours after administration of I-123 Iolopride (IBZM) and their images were evaluated qualitatively and quantitatively. To measure the relative density of the D(2) receptors, the studies were registered to a common space in which the structures to be analyzed were delimited over a RM template. Caudate/frontal (C/FI) and putamen/frontal (P/FI) activity indexes were obtained. RESULTS: Of total, 10 patients presented normal IBZM uptake (C/FI of 1.23 + or - 0.13; P/FI of 1.53 + or - 0.11). The 16 studies listed as abnormal were divided into 2 degrees: (I) appearance of thalamic activity with preserved striatal uptake and (II) thalamus and frontal increased uptake with decrease of striatal activity. In the patients with abnormal patterns, the region that showed a greater reduction of uptake was the putamen (P/FI of 1.1 + or - 0.07 for degree 1, P < 0.05 and P/FI of 1.25 + or - 0.19 for degree 2, P < 0.001). For the differential diagnosis of Parkinson disease in relation to the atypical parkinsonisms, the sensitivity was 68.4% (confidence interval, 51.9-87.6) and the specificity was 57.1% (confidence interval, 20.2-88.2). The patients with Parkinson disease with longer evolution times showed a decrease of D(2) activity (3/7). CONCLUSION: The appearance of thalamic activity may be an early indicator of a decrease of D(2) striatal receptors in atypical parkinsonisms and in patients with long-term Parkinson disease. PMID- 20305410 TI - Impact of FDG PET/CT on delineation of the gross tumor volume for radiation planning in non-small-cell lung cancer. AB - PURPOSE: Computed tomography (CT) remains the gold standard for delineation of tumor volumes for radiotherapy (RT) planning. However, positron emission tomography (PET) overlay on CT has shown to impact the gross target volume (GTV), decrease intraobserver variability, and change the treatment planning in a significant number of patients. The objective of this study was to evaluate the influence and accuracy of FDG PET in GTV definition as a complementary modality to CT for patients with non-small-cell lung carcinoma at Vanderbilt University Medical Center. METHODS: Data from 11 consecutive patients with non-small-cell lung carcinoma, which were referred to FDG PET/CT for initial staging and RT planning were analyzed retrospectively. All patients had undergone routine staging using a RT noncontrasted CT. Both the RT CT and PET/CT images were acquired using standard protocols but with the patients positioned in the same RT immobilization devices. Both the CT and PET/CT images were transferred to the RT planning workstation for contouring. GTV, pathologic nodal and metastases volumes were first defined in the conventional manner based on RT CT. The FDG PET and RT CT planning image datasets were coregistered with the help of the transmission CT from PET/CT. FDG PET GTVs were determined by a team of radiation oncologists and nuclear physician with expertise in PET/CT, and displayed simultaneously with the CT contours. The RT CT and PET GTV were measured and the percent difference was calculated for the primary tumor, pathologic lymph nodes, and distant metastases. A difference of 15% was considered significant. RESULTS: The primary tumor GTV was decreased in 36% (n = 4) of patients by differentiating atelectasis and postobstructive pneumonia from tumor, and increased GTV in 27% (n = 3) of patients by detecting additional tumor burden. Increased nodal disease burden was detected in 18% (n = 2) of patients. The use of PET/CT changed treatment from curative to palliative by detecting distant metastasis in 27% (n = 3) of patients. CONCLUSIONS: Our results are consistent with the published data of PET/CT altering GTV in a significant number of patients, detecting tumor spread to additional lymph nodes and distant metastases. While these advantages support the use of PET/CT in RT planning, it remains unknown what impact this will have on patient outcomes. PMID- 20305411 TI - Hepatobiliary scan findings in chronic cholecystitis. AB - PURPOSE OF THE REPORT: Hepatobiliary scintigraphy, most often referred to as the HIDA scan, is often performed to assess cystic duct patency or occlusion in patients with suspected acute cholecystitis. The imaging diagnosis of chronic cholecystitis is generally made by sonographic demonstration of calculi in a setting of chronic recurrent abdominal pain or nonspecific dyspeptic symptoms. When a stone blocks the gallbladder neck or cystic duct, it precipitates an attack of acute cholecystitis that could be confirmed by performing the HIDA scan. In the course of performing HIDA studies, several incidental findings suggesting chronic cholecystitis may be encountered. Recognition of these suggestive patterns should increase the suspicion of chronic disease that can be further confirmed with sonography, gallbladder ejection fraction determination with sincalide cholescintigraphy, or other clinical findings. MATERIALS AND METHODS: The material selected for this atlas is accumulated from many years of experience with HIDA scan. Illustration of the several scintigraphic patterns suggesting chronic rather than acute cholecystitis is presented to familiarize the reader with these findings. Correlation with clinical, radiologic, and pathologic findings is presented, as well. RESULTS AND CONCLUSIONS: The illustrated findings, though not definitive, may explain the etiology of the underlying symptoms of chronic cholecystitis and direct further management. PMID- 20305412 TI - The 2010 meeting of the American College of Nuclear Medicine. PMID- 20305413 TI - Visualization of cardiac metastasis from medullary thyroid carcinoma on F-18 DOPA PET/CT scan. PMID- 20305414 TI - Synchronous adenocarcinoma of the appendix demonstrated on F-18 FDG PET/CT. PMID- 20305415 TI - Recurrent colon cancer involving the urinary bladder identified with F-18 FDG PET/CT after forced diuresis. PMID- 20305416 TI - Sebaceous carcinoma of the parotid gland: F-18 FDG PET/CT findings. PMID- 20305417 TI - Isolated facial muscle metastasis from renal cell carcinoma on F-18 FDG PET/CT. PMID- 20305418 TI - Incidental early stage endometrial adenocarcinoma diagnosed by F-18 FDG PET-CT, which was negative on ultrasound and nonspecific on MRI. PMID- 20305419 TI - Subcutaneous metastases of colorectal cancer detected with PET/CT. AB - Cutaneous and subcutaneous metastases of colorectal cancer is rare. The authors present a case of a 63-year-old man with colorectal carcinoma, who underwent preoperative staging with positron emission tomography/computed tomography (PET/CT). PET/CT demonstrated intensely increased uptake in the subcutaneous nodular lesion in the anterior surface of the right thigh. Histopathological examination of the excised subcutaneous nodular lesion revealed adenocarcinoma metastases. PMID- 20305420 TI - Occult prolactinoma diagnosed by FDG PET/CT. PMID- 20305421 TI - Malignant transformation in an area with elevated F-18 FDG uptake within a low metabolic benign neurofibroma. PMID- 20305422 TI - Varicose vein as a cause of increased FDG uptake. PMID- 20305423 TI - Meckel's diverticulum and intestinal duplication detected by Tc-99m pertechnetate scintigraphy. PMID- 20305424 TI - Appendiceal carcinoid mimicking a Meckel's diverticulum on Tc-99m pertechnetate imaging. PMID- 20305425 TI - Congenital hiatus hernia identified retrospectively on pediatric pertechnetate imaging. PMID- 20305426 TI - FDG uptake in fat necrosis following transverse rectus abdominis myocutaneous (TRAM) flap reconstructed breasts: 3 cases. PMID- 20305427 TI - Pulmonary artery aneurysm with false-positive FDG PET in a patient with Behcet disease. PMID- 20305428 TI - Tc-99m methylene diphosphonate uptake by numerous phleboliths in the lower extremity detected incidentally during bone scintigraphy. PMID- 20305429 TI - Butterfly vertebra: a diagnostic pitfall on bone scintigraphy. PMID- 20305430 TI - Extracardiac uptake on myocardial perfusion imaging in a patient with diaphragmatic paralysis and Chilaiditi's sign. PMID- 20305431 TI - Pulmonary hydatid cyst detected on FDG PET-CT. PMID- 20305432 TI - Demonstration of a tubercular fistula-in-ano on F-18 FDG PET/CT. PMID- 20305433 TI - Current readings in nuclear medicine. PMID- 20305434 TI - Significance of lymphovascular invasion in sporadic colorectal cancer. PMID- 20305435 TI - Prognostic significance of lymphovascular invasion in sporadic colorectal cancer. AB - PURPOSE: It remains unclear whether lymphovascular invasion marks a poor prognosis for patients with sporadic colorectal cancers. Here, we analyzed the association between lymphovascular invasion and the clinicopathological features and prognosis of sporadic colorectal cancer patients. METHODS: The clinicopathological features and prognosis of 2417 patients with sporadic primary colorectal cancer who underwent an operation at the Asan Medical Center between January 1998 and December 2002 were examined. The patients' clinicopathological parameters and follow-up and survival data were obtained from a prospectively collected database. RESULTS: Of the 2417 patients, a lymphovascular invasion positive tumor was detected in 610 (25.2%). Compared with patients with lymphovascular invasion-negative tumors those with lymphovascular invasion positive tumors were older (P < .001) and had higher preoperative serum carcinoembryonic antigen levels (P = .011). Their tumors were also more likely to be poorly differentiated (P < .001) and more advanced in terms of T and N categories (P < .001 and P < .001, respectively). The lymphovascular invasion positive tumors were also more likely to have metastasized systemically (P < .001). Although lymphovascular invasion-positive and lymphovascular invasion negative tumors metastasized equally frequently to the liver, lung, peritoneum, and bone, lymphovascular invasion-positive tumors metastasized to systemic lymph nodes more often (P < .001). These tumors also recurred at systemic lymph nodes after curative intent surgery more often (P = .007). Lymphovascular invasion positive status was an independent unfavorable prognostic factor for the 5-year overall and 5-year disease-free survival of patients with sporadic colorectal cancer (P < .001 and P < .001, respectively). CONCLUSION: Lymphovascular invasion positive status could be used to identify patients with sporadic primary colorectal cancer with aggressive tumors and as a factor that independently indicates an unfavorable prognosis. PMID- 20305436 TI - Acuity and survival in colon cancer surgery. AB - PURPOSE: Reports indicate that up to 40% of patients with colon cancer require nonelective resection, which has been shown to portend worse long-term prognosis compared with elective resection. We used a national database to identify specific preoperative, perioperative, and postoperative factors mediating the acuity-survival relationship in an effort to identify areas of medical practice that can serve as targets for improvement in cancer care. METHODS: We used the Surveillance, Epidemiology and End Results-Medicare-linked database to identify non-health maintenance organization-enrolled people aged 66 years and older who were diagnosed with stages I to III colon cancer between 1996 and 2003 (N = 30,685). Using stepwise, multivariate Cox regression, disease-specific survival was compared in patients undergoing elective vs nonelective resection. Adjustment for preoperative, perioperative, and postoperative variables was performed to identify factors contributing to the acuity-survival relationship. RESULTS: Five year disease-specific survival was 86.3% after elective and 75.4% after nonelective colon resection (hazard ratio, 1.92; P < .001). A significant proportion of this disparity was the result of differences in stage and patient characteristics, particularly age and comorbidity burden, at the time of resection. Differences in adequacy of nodal assessment and the use of surveillance colonoscopy and adjuvant chemotherapy, however, also contributed to the disparity. After adjustment for these factors, the hazard ratio for nonelective resection was 1.30 (P < .001). CONCLUSION: Nonelective resection of colon cancer is associated with poor long-term prognosis compared with elective resection. Disease-specific survival among patients undergoing nonelective surgery may be improved by addressing insufficient nodal assessment, inadequate follow-up care, and underutilization of appropriate, adjuvant chemotherapy. PMID- 20305437 TI - Impact of hospital institutional volume on postoperative mortality after major emergency colorectal surgery in English National Health Service Trusts, 2001 to 2005. AB - PURPOSE: The aim of this study was to investigate the effects of institutional volume on postoperative mortality in patients undergoing emergency major colorectal surgical procedures in England between 2001 and 2005. METHODS: All of the emergency excisional colorectal procedures performed between the above dates were included from the Hospital Episode Statistics data set. Institutions were divided into high-, medium-, and low-volume tertiles according to the total major emergency colorectal caseload. RESULTS: During the study period, 37,094 emergency excisional colorectal procedures were performed in 166 English National Health Service institutions. Overall 30-day postoperative mortality was 15.49%, increasing to 29.18% at 1 year after surgery. Overall 30- and 365-day mortality rates were similar among institutional volume tertiles (P > .05) after adjustment for age, sex, social deprivation, diagnosis, procedure type, and comorbidity score. CONCLUSION: Hospital Episode Statistics data suggest that institutions with high volumes of emergency colorectal caseload do not demonstrate lower mortality after emergency major excisional colorectal surgery. PMID- 20305438 TI - Long-term outcomes after local excision and radical surgery for anal melanoma: data from a population database. AB - PURPOSE: Anal melanoma is rare and associated with a poor outcome. Previous studies that have reported outcomes after surgical treatment are limited by both small number of participants and treatment at single centers only. This study evaluates survival of patients undergoing surgery for anal melanoma from a prospective, population-based database. METHODS: Characteristics and survival of patients undergoing rectal resection or local excision for anal melanoma of the anus, anal canal, and overlapping region of the rectum from 1982 to 2002 were obtained from the Surveillance, Epidemiology and End Results database and compared. RESULTS: A total of 160 patients were included in the study. Details of previous surgical procedures were available for 109 of the study patients: 60 (55%) underwent local excision and 49 (45%) rectal resection. Patients who underwent local excision were significantly older (73.5 vs 65.1 years, P < .001), whereas those who had undergone rectal resection had a greater proportion of regional disease (73.5% vs 16.7%, P < .001). The median survival of the 2 groups was similar (rectal resection vs local excision: 17 vs 28 months, P = .3). Rectal resection and local excision were associated with similar survival for patients in both regional (P = .6) and localized (P = .95) stages. Outcomes for patients who were appropriately pathologically staged after rectal resection depended on localized vs regional stage (5-year survival: 43.1% vs 12.5%, P = .17). Survival for patients in localized and regional stages who underwent rectal resection was similar to that for patients with corresponding clinical stage who underwent local excision. CONCLUSION: Survival of patients with anal melanoma is similar after local excision or rectal resection irrespective of whether patients have localized or regional stage of disease. PMID- 20305439 TI - Abnormal colonic motility: a possible association with urge fecal incontinence. AB - PURPOSE: Fecal incontinence is a distressing condition affecting up to 7% of the population. Severe urgency is a symptom associated with hypersensitivity of the rectum, a common finding in both fecal incontinence and irritable bowel syndrome. The purpose of this study was to investigate whether patients with fecal incontinence, urgency, and rectal hypersensitivity have abnormal hindgut motility, suggestive of a more generalized motility problem. METHODS: Eleven females with urgency-associated incontinence and without anal sphincter injury were compared with 5 controls. After full clinical, ultrasonographic, and physiological assessment, patients underwent prolonged colonic manometry studies. Motility patterns were recorded and, in particular, the response to a standard gastrocolic reflex was noted. RESULTS: Rectal sensation values in patients were as follows: first sensation, 22 (range, 5-58) mls; desire to defecate, 31 (range, 13-166) mls; and maximum tolerated volume, 64 (range, 21-254) mls. Compared with controls, patients had significantly higher numbers of 1) low amplitude waves (>5 mmHg) in both the sigmoid colon (101 vs 46.5; P = .028) and the descending colon (101.5 vs 41; P = .036) in the hour before the meal stimulus, and 2) high amplitude waves (>50 mmHg) in the sigmoid colon (2 vs 0; P = .006) in the fasting state. CONCLUSION: Patients with fecal incontinence associated with severe urgency may have rectal hypersensitivity and a more global colonic motility problem similar to irritable bowel syndrome. PMID- 20305440 TI - Six years of experience with sacral nerve stimulation for fecal incontinence. AB - PURPOSE: Sacral nerve stimulation is one of many new surgical modalities for fecal incontinence. Short-term results from sacral nerve stimulation have been more encouraging than those from other modalities. The aim of this study was to report the outcome of percutaneous nerve evaluation tests and sacral nerve stimulation for the treatment of fecal incontinence from a single center covering a period of 6 years since the procedure was introduced. METHODS: All of the candidates for a percutaneous nerve evaluation test and sacral nerve stimulation seen at our anal physiology unit between March 2001 and March 2007 were included in the study. RESULTS: A total of 177 patients with fecal incontinence (160 females), median age 59.5 (range, 27-88) years, underwent a percutaneous nerve evaluation test. Of these patients, 142 (80%) had a positive test, including 21 of 25 (84%) patients who required a repeat percutaneous nerve evaluation test. Because of a functional failure, 16 patients underwent a revision of the permanent electrode, 7 of whom (44%) were satisfied with the functional result after the revision. Of 126 patients, 15 (12%) have undergone an explantation, with an infection rate of only 1.6%. Overall, after a median follow-up of 24 (range, 3-72) months, the median Wexner incontinence score decreased from 16 (range, 6-20) to 10 (range, 0-20) (P < .0001). In the 10 patients who underwent at least 6 years of treatment, the effect was sustained, as the median Wexner incontinence score decreased from 20 (range, 12-20) to 7 (range, 2-11) (P < .0001). CONCLUSION: Sacral nerve stimulation is a simple, safe, and minimally invasive technique with low morbidity and excellent results, which appear to be maintained for the first 6 years after the procedure. For patients who underwent the treatment, median Wexner incontinence score decreased significantly after a median follow-up of 24 (range, 3-72) months. Twelve percent were explanted. The infection rate was 1.6%. PMID- 20305441 TI - Is sacral neuromodulation for fecal incontinence worthwhile in patients with associated pelvic floor injury? AB - PURPOSE: It has been shown that vaginal delivery may result in pelvic floor injury. Until now it is unknown whether this type of injury plays a role in the etiology of fecal incontinence and whether it affects the outcome of treatment. The aim of the present study was to assess the prevalence of pelvic floor injury in patients with fecal incontinence who were eligible for sacral neuromodulation and to determine whether sacral neuromodulation is worthwhile in patients with pelvic floor injury. METHODS: All women with fecal incontinence who were eligible for sacral neuromodulation in the past were invited to participate in the present study. With transperineal ultrasound, which has been developed recently, pelvic floor integrity was examined in 46 of the 66 patients (70%). Follow-up was obtained from a standardized questionnaire. RESULTS: Pelvic floor injury was found in 29 of the 46 participants (63%). No differences regarding the efficacy of sacral neuromodulation were found between patients with and those without pelvic floor injury. Successful test stimulation was obtained in 86% of the patients with pelvic floor injury and in 71% of the patients without pelvic type injury. After implantation of a definitive pulse generator, a successful outcome was found in 84% of the patients with pelvic floor injury and in 75% of the patients with an intact pelvic floor. CONCLUSION: Pelvic floor injury is present in the majority of incontinent patients who were eligible for sacral neuromodulation. This type of injury seems to have no detrimental effect on the treatment outcome. PMID- 20305442 TI - Sacral nerve modulation in the treatment of fecal incontinence following repair of rectal prolapse. AB - PURPOSE: Persistent or newly-diagnosed fecal incontinence following surgical repair of rectal prolapse has been reported in up to 30% of all treated patients. This study tried to evaluate the role of sacral nerve modulation as a potential treatment for this problem. PATIENTS AND METHODS: The medical records of 11 patients (all female; median age, 59 years) in 2 coloproctology centers were retrospectively analyzed. All of the patients had been treated for fecal incontinence by sacral nerve modulation, following transabdominal or transanal repair of rectal prolapse. After a median history of 36 (11-72) months following surgery, patients complained about fecal incontinence (median Cleveland Clinic Incontinence Score, 15 (13-20)), and sacral nerve modulation was proposed. The effect of sacral nerve modulation on the Cleveland score, as well as on the quality of life scoring system of The American Society of Colon and Rectal Surgeons, was evaluated. RESULTS: Based on their continence diaries, 9 of 11 patients reported an improvement of their fecal incontinence during the screening period, and proceeded to a permanent implant. After a median follow-up time of 36 (12-72) months, fecal incontinence scores dropped from a median of 15 (13-20) preoperatively to a median of 5 (3-7) in all implanted patients (P < .01). Quality of life analysis for all implanted patients showed significant improvement in all 4 domains (lifestyle, coping behavior, depression, and embarrassment (P < .01)). CONCLUSION: In this series, with a limited number of patients, sacral nerve modulation has shown a positive effect on the treatment of both persistent and newly-reported fecal incontinence after surgical repair of rectal prolapse. PMID- 20305443 TI - Percutaneous tibial nerve stimulation for the treatment of urge fecal incontinence. AB - PURPOSE: Percutaneous tibial nerve stimulation has been shown to be an effective treatment in patients with urinary disorders, but its benefit in fecal incontinence is uncertain. This study aimed to assess the efficacy of percutaneous tibial nerve stimulation in the treatment of urge fecal incontinence. METHODS: This prospective study, conducted over a 14-month period, assessed 31 patients with urge fecal incontinence treated with percutaneous tibial nerve stimulation. The outcomes measured were: 1) reduction in fecal incontinence episodes, 2) improvement in Cleveland Clinic incontinence scores, and 3) improvement in ability to defer defecation. All analysis was performed on an intention-to-treat basis. RESULTS: The median follow-up was 9 months (range, 3 14). Twenty-one (68%) patients improved following percutaneous tibial nerve stimulation and remain satisfied with the clinical response. Median fecal incontinence episodes per week declined from 4 (range, 0-30) to 0 (range, 0-27) (P < .0001). Median Cleveland Clinic incontinence scores declined from 13 (range, 5-20) to 7 (range, 0-20) (P < .0001). Ability to defer defecation was improved significantly (P < .0001). No morbidity was encountered for any patient. CONCLUSION: This preliminary study demonstrates that percutaneous tibial nerve stimulation is an effective and very well tolerated treatment for patients with urge fecal incontinence with particular improvement in reducing fecal urgency. PMID- 20305444 TI - Laparoscopic rectal surgery: does immediate outcome differ in respect to sex? AB - PURPOSE: This study analyzed the immediate postoperative outcome of the laparoscopic approach to the rectum in relation to the sex of the patient. METHODS: Two hundred thirty-nine patients were included in our study. The inclusion criterion was rectal cancer <15 cm from the anal margin. Exclusion criteria were the presence of anesthetic contraindications for pneumoperitoneum, T4, pancolonic polyposis, and ulcerative colitis. The parameters analyzed included demographics, comorbidities, previous abdominal surgery, preoperative chemoradiotherapy, body mass index, operative time, type of operation, difficulty score, conversion, hospital stay, postoperative morbidity according to the Dindo classification, and histopathologic analysis. Analysis was performed on an intention-to-treat basis. Results are given as number of cases and percentages for categorical data, and as median and 95% confidence interval for quantitative variables. Data were analyzed by use of bivariate analysis, contingency tables, and chi or Fisher exact tests for categorical variables, and ANOVA or t test for quantitative variables. The statistical significance level was set at 5% (alpha = 0.05), and two-tailed tests were used throughout. RESULTS: We did not find any statistical differences related to sex in the global series, pure laparoscopy, or converted patients in relation to mortality, conversion, anastomotic leakage, morbidity, reintervention, and morbidity classification according to Dindo (P > .05). We only observed a trend in relation to a longer duration of surgery in men. This was statistically significant in the low anterior resection subgroup (P = .02) and in the overall series (P = .002). Statistical analysis also showed that postoperative stay was longer in men after an anterior resection (P = .015). CONCLUSION: We believe that no important differences exist in perioperative outcomes between men and women after a laparoscopic approach to rectum cancer. PMID- 20305445 TI - The short-term effect of neoadjuvant chemoradiation on anorectal function in low and midrectal cancer: analysis using preoperative manometric data. AB - PURPOSE: The purpose of this study was to evaluate the short-term preoperative effects of neoadjuvant chemoradiation on anorectal function, excluding the bias of postoperative impairment. METHODS: We analyzed 80 patients on whom preoperative anorectal manometry data were available for both prechemoradiation and postchemoradiation. Patients were divided into 2 groups according to the tumor location; lower rectum (n = 52) and mid rectum (n = 28). The paired t test was used to compare prechemoradiation and postchemoradiation parameters including the mean resting pressure, maximum squeeze pressure, percentage asymmetry of the resting and squeeze sphincter, length of the high-pressure zone, rectal sensory threshold, and rectal compliance. RESULTS: In patients with a lower rectal cancer, there were significant differences in the percentage asymmetry of the squeeze sphincter (27.81 +/- 6.46 vs 25.38 +/- 5.93%, P < .01), length of the high-pressure zone (2.14 +/- 0.74 vs 2.33 +/- 0.72 cm, P = .05), and rectal compliance (1.14 +/- 0.41 vs 1.02 +/- 0.40 mL/mmHg, P = .04). In patients with midrectal cancer, only the mean resting pressure increased significantly (45.08 +/- 18.57 vs 52.83 +/- 17.87 mmHg, P < .01). Clinical symptom evaluation demonstrated a significant decrease in the number of defecations and the frequency of tenesmus. CONCLUSION: Neoadjuvant chemoradiation did not impair overall short-term sphincter function significantly, regardless of the location of the primary tumor. Although there was a decrease in rectal compliance, it seemed that the tumor-downsizing effect compensated the expected worsening of anorectal function in the early postchemoradiation period. PMID- 20305446 TI - Spectrum of MLH1 and MSH2 mutations in Chilean families with suspected Lynch syndrome. AB - PURPOSE: Lynch syndrome is the most common inherited syndrome of colorectal cancer, caused principally by germline mutations in MLH1 and MSH2. We report our experience with genetic screening in the diagnosis of Lynch syndrome in Chile, a country previously underserved in the capacity to diagnose hereditary colorectal cancer. METHODS: Families from our Familial Colorectal Cancer Registry were selected for this study if they fulfilled either Amsterdam I/II or Bethesda criteria for classification of Lynch syndrome. Analysis of colorectal tumors from probands included a microsatellite instability study and immunohistochemical evaluation for MLH1 and MSH2. Screening of germline mutations was performed by single-strand conformation polymorphism analysis and DNA sequencing. RESULTS: A total of 21 families were evaluated, 14 meeting Amsterdam criteria and 7 meeting Bethesda criteria. Tumors in 20 families (95%) showed microsatellite instability (19 high and 1 low) and 9 of these 20 families (45%) harbored a germline mutation (7 of 13 Amsterdam and 2 of 7 Bethesda families). Of the 9 mutations identified, 6 were in MLH1 and 3 in MSH2. Two of the mutations were novel, 3 were previously found in 1 to 2 European populations, and 4 were previously found in various ethnic populations worldwide. Only 2 mutations were previously found in another Latin American population (Colombia). In our probands, colorectal cancer was located mainly (57%) in the right or transverse colon. Pedigree information from 104 family affected members of 21 studied families showed endometrial cancer to be the most frequent primary extracolonic tumor, accounting for 15.1% of total cases, followed by stomach (13.2%) and breast cancer (11.3%). Analysis of mitochondrial DNA haplotypes showed a strong Amerindian genetic component in 15 (71.4%) of the 21 families analyzed. CONCLUSION: The study of Lynch syndrome in families of different ethnic origins contributes to the definition of genetic and clinical differences among populations. Wide distribution in other ethnic populations strongly suggests varying origins of 4 the mutations found. Although cancer phenotype was consistent with those from other Latin American populations, only 2 of 9 mutations were shared with other South American populations and 2 novel mutations were found. The Chilean population is considered to be an admixture of Amerindian and European-mainly Spanish-populations, producing an ethnic group with significant genetic differences from populations previously studied. PMID- 20305447 TI - Treatment of chronic anal fissures and associated stenosis by autologous adipose tissue transplant: a pilot study. AB - PURPOSE: A substantial body of recent evidence suggests that autologous adipose tissue transplant promotes healing in different lesions associated with local ischemia. We report the outcome of lipoaspirate transplant in hard-to-treat chronic anal fissures. METHODS: Eight patients were included in this pilot study, 5 with single and 3 with multiple fissures. All had intense anal pain and had previously undergone proctologic surgery, with internal sphincterotomy performed in 6 patients. Severe stenosis was present in 3 patients and moderate stenosis in 2. Preoperative assessment included anoscopy, anorectal manometry, colonoscopy, and microbiological tests to exclude inflammatory, neoplastic, or infectious diseases. Surgical treatment consisted of transplant of purified autologous fat retrieved from the hypogastrium. Follow-up was scheduled after 1 week, at 2, 3, 6, and 12 months, and thereafter on a yearly basis. RESULTS: All of the patients were discharged several hours after surgery. No early postoperative complication was observed. Complete healing and pain remission were achieved in 6 patients (75%), 4 of whom were treated in a single session, whereas 2 patients required 2 and 3 sessions. Anal stenosis was resolved in 4 of 5 patients (80%). The therapy was unsuccessful in 2 patients (25%). Mean follow-up was 18 months (range, 3-36 months). CONCLUSION: Perianal autologous fat transplant can be safely performed for the treatment of complex anal fissures. It is well tolerated and offers encouraging results, although further research is warranted because of the small number of patients treated and the relatively short follow-up time. PMID- 20305448 TI - Practical and effective stomal sphincter creation: evaluation in pigs. AB - PURPOSE: Stoma creation frequently presents complications for which there is no satisfactory surgical solution. We reexamined the feasibility of managing stoma continence with an artificial sphincter, addressing the outstanding issues of geometry, electrode disposition, and fatigue resistance. METHODS: In 6 pigs, 1 rectus abdominis muscle was preconditioned with electric stimulation for 4 weeks by an implanted stimulator. A sphincter was then constructed and tested for its ability to provide continence against saline at a typical intestinal pressure. The result was compared with a sphincter fashioned from the unconditioned contralateral (control) muscle. In each case, stimulation was applied alternately to longitudinal segments. RESULTS: A 2-layered wrap was required to achieve continence. Sphincters created from the preconditioned muscles could sustain continence continuously for at least 90 minutes. CONCLUSION: This study establishes a practical approach to the creation of a sphincter from the rectus abdominis muscle in stoma patients. Continence can be achieved only with a double layered wrap. Fatigue during long-term operation can be avoided by a combination of preconditioning and segmental stimulation of intramuscular nerve branches. PMID- 20305449 TI - Inhibition of hyaluronan synthase-3 decreases subcutaneous colon cancer growth in mice. AB - PURPOSE: Hyaluronan and hyaluronan synthases have been implicated in cancer progression. Hyaluronan synthase-3 is up-regulated in metastatic colon cancer cells (SW620), and its expression mediates cellular growth in vitro. We hypothesized that inhibition of hyaluronan synthase-3 would decrease tumor formation and/or alter the pattern of metastasis in mouse models of colon cancer growth. METHODS: Hyaluronan synthase-3 was inhibited in SW620 cells by transfection with small interfering RNA (silenced cells); a scrambled sequence served as a negative control. To study primary tumor growth, transfected cells were injected into the flanks of BALB/c nude mice. To study metastasis, an orthotopic model was used. Metastases were confirmed histologically. Student t test and Fisher exact probability test were used for statistical analysis. RESULTS: Inhibition of hyaluronan synthase-3 significantly decreased subcutaneous tumor growth; tumor weight was 0.94 +/- 0.17 g in the hyaluronan synthase-3 silenced group vs 1.70 +/- 0.26 g in the control scrambled group (P < .01). In contrast, metastases were similar in both groups: liver metastases were present in 22% of the silenced group vs 11% of the scrambled group; lung metastases were present in 6% of the silenced group vs 0% of the scrambled group (P = not significant). CONCLUSION: Inhibition of hyaluronan synthase-3 expression in SW620 colon cancer cells decreases subcutaneous tumor growth in mice, but has less of an effect on lung and liver metastases. This observation suggests that hyaluronan synthase-3 may enhance primary colon cancer growth. PMID- 20305450 TI - Canadian Association of General Surgeons, the American College of Surgeons, the Canadian Society of Colorectal Surgeons, and the American Society of Colon and Rectal Surgeons: evidence based reviews in surgery - colorectal surgery. PMID- 20305451 TI - Endorectal advancement flap for cryptoglandular or Crohn's fistula-in-ano. AB - PURPOSE: Objectives of surgical treatment for transsphincteric and complex anorectal fistulas are the successful elimination of current/recurrent disease and the preservation of sphincter function. The concept of endorectal advancement flaps is to preserve the sphincter by closing off the primary opening by means of a mobilized flap. We performed a systematic review of the literature to assess the role of this technique. METHODS: A literature search on transanal rectal advancement flaps to treat cryptoglandular or Crohn fistula-in-ano was performed for the 30-year period between 1978 and 2008. Rectovaginal/rectourinary or cancer related fistulas were excluded. Each study was examined for length of follow-up and the 2 major end points: success rate and incontinence rate. RESULTS: From 35 studies with 2065 patients, we identified 1654 patients undergoing endorectal advancement flaps for cryptoglandular or Crohn disease. Four hundred eleven subjects were excluded (319 rectovaginal/rectourinary fistulas; 92 other causes). The quality of the reports was limited (low-level evidence) with numerous structural and design flaws. Weighted success and incontinence rates were 80.8%/13.2% for cryptoglandular and 64%/9.4% for Crohn fistulas. CONCLUSION: Endorectal advancement flap is one tool, although not a perfect one, to treat complex anorectal fistulas of cryptoglandular or Crohn origin. Higher level evidence would be needed for comparison with other surgical techniques. PMID- 20305453 TI - An innovative technique for colorectal specimen retrieval: a new era of "Natural Orifice Specimen Extraction" (N.O.S.E.). PMID- 20305452 TI - Single-access laparoscopic colectomy with a novel multiport device in sigmoid colectomy for colon cancer. AB - PURPOSE: Laparoscopic-assisted colectomy is a common procedure for colorectal disease, and laparoscopic colectomy from a single access point is rapidly evolving. This report describes the use of single-access laparoscopic colectomy (SALC) with a novel multiport device in sigmoidectomy for colon cancer. METHODS: Data were collected retrospectively on 5 patients who underwent the procedure for colon cancers in the period from November 2008 through January 2009. The abdomen was approached through a 3- to 4-cm incision via the umbilicus in every case. To ensure maintenance of the pneumoperitoneum, the procedure was performed with a specially developed multiport device enveloped by a glove containing 3 5-mm ports. In all 5 patients, the root of the inferior mesenteric artery was isolated and divided at the distal side where the left colic artery branched off. RESULTS: The median total surgical time was 185 (range, 176-210) minutes. In all patients, surgical blood loss was slight (range, 0-20 mL). Only one patient required conversion into laparoscopic-assisted colectomy by the addition of 2 ports, because the location adjacent to the descending colon made it necessary to mobilize the splenic flexure. The median number of harvested lymph nodes was 17 (range, 12-24). No postoperative complications occurred. The postoperative hospital stay was 7 days for every patient. CONCLUSIONS: Single-access laparoscopic sigmoidectomy seems to be feasible and safe when performed by experienced laparoscopic surgeons who are familiar with the unique principles of this procedure. Additional experience and continued investigations are warranted. PMID- 20305456 TI - Letter to the editor. PMID- 20305457 TI - Is it time to pull the plug on 12-hour shifts?: Part 2. Barriers to change and executive leadership strategies. AB - This article is part 2 of the series "Pulling the Plug on 12-Hour Shifts." In part 1 (March 2010), the authors provided an update on recent evidence that challenges the current scheduling paradigm that supports the lack of safety of long work hours. Part 2 describes the barriers to change and challenges for the nurse executive in moving away from the practice of 12-hour shifts. This is an executive-level analysis of barriers and recommends strategies for change. Translation of evidence into administrative practice requires examination of external environmental factors, internal system consequences, organizational culture, and measures of executive performance. PMID- 20305458 TI - Positive deviance: an elegant solution to a complex problem. AB - As systems evolve over time, their natural tendency is to become increasingly more complex. Studies in the field of complex systems have generated new perspectives on management in social organizations such as hospitals. Much of this research appears as a natural extension of the cross-disciplinary field of systems theory. This is the 13th in a series of articles applying complex systems science to the traditional management concepts of planning, organizing, directing, coordinating, and controlling. This article provides one example of how concepts taken from complex systems theory can be applied to real-world problems facing nurses today. PMID- 20305459 TI - Preparing tomorrow's leaders: a review of the issues. AB - This biannual department, sponsored by CGEAN, provides information updates to nurse leaders on educational trends, issues, and research important for effective nursing and health system administration. The CGEAN Web site can be accessed at http://www.cgean.org. PMID- 20305460 TI - Accreditation and certification for evidence-based design. AB - The Evidence-Based Design Accreditation and Certification (EDAC) is a professional certification that validates that individuals have a core body of knowledge and experience necessary to lead and engage in an evidence-based design process for healthcare facilities. This bimonthly department expands nurse leaders' knowledge and competencies in health facility design and enables them to lead in design efforts. In this article, the vision and mission of EDAC and specific content are shared to increase nurse leaders' awareness of the certification when interviewing prospective architectural firms or for nurse leaders who aspire to have a career in the healthcare design field. PMID- 20305461 TI - Implementing an electronic change-of-shift report using transforming care at the bedside processes and methods. AB - Bedside nurses are well positioned to make changes that positively affect operations and practice. Using Transforming Care at the Bedside processes and methods, the authors describe the clinical nurse-led development, testing, and implementation of an electronic template and process for change-of-shift report. Outcomes included a reduction in time spent in change-of-shift reports, reduced end-of-shift overtime, and a more standardized process, with staff perceived improved information quality and satisfaction with the process. PMID- 20305462 TI - Losing the moment: understanding interruptions to nurses' work. AB - Interruptions in the nursing work environment can have significant, detrimental effects on patient safety. This mixed-method study used work observation and focus groups to explore interruptions in nursing work. A large number of interruptions were reported. Causes of interruptions are analyzed, and systems processes for reducing these in the future are discussed. PMID- 20305463 TI - Attacking the problem of hospital diversion: a report of success. AB - Hospital diversion is a critical issue for hospitals that affects safety and overall patient care. At Wishard Hospital, a public hospital with a level 1 trauma center, we critically reviewed our diversion policies and implemented a series of changes. This hospital-wide process significantly decreased our diversion rates, thereby providing consistent and safe care to our community. PMID- 20305464 TI - Listening to nursing leaders: using national database of nursing quality indicators data to study excellence in nursing leadership. AB - There are varying and overlapping leadership characteristics that exemplify excellence in nursing leadership. To assess aspects of leadership that helps create a healthy work environment that supports nurses' provision of quality care at the bedside, the authors used a national survey instrument to examine the characteristics of nurse managers identified as excellent nurse leaders by their staff. The authors discuss their findings and a proposed theoretical model to explain specific nursing leadership characteristics that support staff nurse job satisfaction and retention. PMID- 20305466 TI - Effects of smoking cessation on gastric emptying in smokers. AB - BACKGROUND: Smoking cessation can lead to changes in appetite and weight gain in some patients; thus, smoking cessation may alter gastrointestinal motility. Effects of smoking cessation on gastric emptying in smokers have not been established. AIM: This study sought to determine how smoking cessation affects gastric emptying in smokers. METHODS: Participant group comprised 53 habitual smokers and 12 healthy nonsmokers. Habitual smokers were treated for 2 months with transdermal nicotine patches. Gastric emptying was studied using C acetate breath tests at the beginning of the study, and at 1 week and 9 weeks after cessation of patch use. Maximal CO2 excretion time (Tmax), CO2 excretion half life (T1/2), and parameters beta and kappa, representing initial and subsequent gastric-emptying phases, respectively, were determined using conventional formulae. RESULTS: Before smoking cessation, Tmax was reached significantly later in smokers (0.94+/-0.3 h, P=0.014) than in controls (0.89+/-0.1 h). At 1 week after the end of treatment, Tmax was significantly decreased (from 1.05+/-0.32 h to 0.72+/-0.64 h, P=0.003). T1/2 also tended to decrease, but not significantly. Although beta was decreased significantly (from 2.46+/-0.40 to 2.17+/-0.58, P=0.022), kappa was unchanged. However, by 9 weeks after the end of treatment, Tmax (1.28+/-0.69 h) had increased to levels seen before treatment. CONCLUSIONS: Smoking cessation temporarily accelerates gastric emptying, and decreases in beta suggest that initial-phase gastric emptying accelerates after smoking cessation. The temporary acceleration of gastric emptying after smoking cessation may be involved in the temporary increase in appetite and weight gain seen after smoking cessation. PMID- 20305465 TI - Nurse managers' decisions: fast and favoring remediation. AB - How do nurse managers make decisions about quality issues on their units? We asked 10 nurse managers in 3 Arizona hospitals to describe how they resolved a recent quality issue. The managers tended to use a linear, but cognitively expensive strategy, often jumping from problem to solution without a clear goal and selecting solutions biased toward remedial education. Decision support tools should help managers think more systemically and efficiently, while encouraging consideration of more alternatives to reach targeted goals. PMID- 20305467 TI - Economic impact of prescreening on gastroenterology outpatient clinic practice. AB - BACKGROUND: Outpatient clinic activity represents a major workload for clinicians. Unnecessary outpatient visits place a strain on service provision, resulting in unnecessary delays for more urgent cases. GOALS: We sought to determine both the impact and economic benefit of employing phone follow-up and physician assistant (PA) triage systems on attendances at a gastroenterology outpatient department. STUDY: We performed a retrospective chart review of all patients attending a gastroenterology outpatient clinic over a 2-week period. Patients were categorized into new or follow-up attendees and the follow-up patients were further subcategorized into 1 of 4 groups: (1) those attending to receive results of investigations requiring no further treatment (group A); (2) those attending to receive results of investigations requiring further treatment (group B); (3) those attending with a chronic gastrointestinal disease requiring no active change in management (group C); (4) those attending with a chronic gastrointestinal disease requiring active change in management (group D). It was assumed that patients in group A could be managed by phone follow-up in place of clinic attendance and patients in group C could be triaged to see a PA. RESULTS: Out of a total of 329 outpatient attendees, 40 (12%) required no active intervention (group A) and would have been suitable for phone follow-up. A further 58 (18%) had stable disease, requiring no change in management and hence, could have been triaged to see a PA. Implementation of phone follow-up and patient review by PA could reduce salary expenses of outpatient practice by 17%. CONCLUSIONS: Our findings support routine prescreening of outpatient attendees to enhance the efficiency of gastroenterology outpatient practice. PMID- 20305468 TI - Anti-Saccharomyces cerevisiae antibodies in first-degree relatives of celiac disease patients. PMID- 20305469 TI - A broad panel of autoantibodies in patients with celiac disease and Crohn's disease. PMID- 20305470 TI - Endovascular treatment of innominate artery occlusion with simultaneous vertebral and carotid artery distal protection: case report. AB - OBJECTIVE: Atherosclerotic stenosis or obstruction of the innominate artery is rare. Traditional surgical management is a technically demanding intervention with acceptable, but not negligible, rates of morbidity and mortality. Endovascular approaches to supraaortic lesions have been successful and are now the preferred treatment for stenoses of the brachiocephalic vessels. The use of cerebral protection devices in subclavian and innominate interventions is less established. CLINICAL PRESENTATION: A 58-year-old woman had Takayasu giant cell arteritis with a history of a left middle cerebral artery stroke 3 weeks after undergoing placement of a left common carotid artery (CCA) stent and right innominate artery stent in 1998. She recently presented with worsening dizziness, ataxia, and right arm numbness and was referred to the endovascular neurosurgery service for management. INTERVENTION: Initial angiography revealed left CCA stenosis and right innominate occlusion. The patient initially underwent left CCA angioplasty, planned as a staged procedure. This was followed by recanalization of the right innominate artery through an approach using both femoral arteries and the right brachial artery. This 3-site technique allowed simultaneous distal protection of both the right cervical vertebral and carotid arteries. CONCLUSION: Reopening a chronically occluded innominate artery risks an embolic shower through both the right vertebral and carotid arteries. Using multiple sites of arterial access, distal protection devices can be deployed in both the cervical vertebral and carotid arteries to reduce the risk of stroke. PMID- 20305471 TI - Delayed facial palsy after the anterior petrosal approach: case report and review of the literature. AB - OBJECTIVE: In this case report, delayed facial palsy developed in a patient without any direct manipulation of the main part of the facial nerve during an anterior petrosal approach. We discuss putative etiologies and management techniques that may help avoid this problem. CLINICAL PRESENTATION: A 21-year-old woman underwent anterior petrosectomy for gross total resection of a low-grade chondrosarcoma. Six days later, the patient presented with left-sided facial weakness in the emergency department. RESULTS: Examination revealed evidence of House-Brackmann grade V/VI left-sided facial palsy, and repeat magnetic resonance imaging revealed diffuse enhancement of the contents of the internal auditory canal that was not present immediately after surgery. After a 10-day course of acyclovir and a tapering dose of methylprednisolone, the facial palsy slowly diminished and resolved 2 months after the onset. CONCLUSION: This unique development of delayed facial palsy after an isolated anterior petrosal approach is evidence that this complication should be considered when dissecting along the floor of the middle fossa. Exposure of the intracranial or intracanalicular segment of the facial nerve is not necessary for delayed facial palsy to develop. Proposed mechanisms (ie, viral reactivation, vasospasm, neural edema) of this condition remain unproven. Prognosis for recovery has been reported to be excellent, with or without treatment. PMID- 20305472 TI - Early endovascular coiling of posterior communicating artery saccular aneurysm in the setting of Staphylococcus bacteremia: case report and review of the literature. AB - OBJECTIVE: Although infectious complications of endovascular aneurysm treatment are in general rare, platinum coil therapy for patients with ruptured cerebral aneurysms and active bacteremia could be expected to carry increased risk. The literature on the timing and safety of endovascular treatment in this setting, however, is limited. In this report, the authors present a case of aneurysmal subarachnoid hemorrhage and active bacteremia in which intravenous antibiotics and early endovascular therapy were successfully used. A review of the literature is also provided. CLINICAL PRESENTATION: A 79-year-old woman presented with Hunt Hess grade 4, Fisher grade 3 + 4 subarachnoid hemorrhage. Blood cultures obtained on admission revealed gram-positive cocci, which later proved to be coagulase negative Staphylococcus. INTERVENTION: Intravenous cefepime and vancomycin were begun soon after admission. A right posterior communicating artery saccular aneurysm was identified on diagnostic cerebral angiography and was treated with bare platinum coils 28 hours after antibiotic therapy was initiated. An extended course of vancomycin was completed. No intracranial infectious complications were noted at 34-month clinical and radiographic follow-up. CONCLUSION: This is the first case report to document the efficacy and safety of early endovascular coil embolization of a ruptured saccular cerebral aneurysm presenting in the context of active bacteremia. Review of the available literature suggests that a similar strategy for ruptured infectious aneurysms may also be safe. Further validation of this approach for both saccular and infectious aneurysms, however, is required. PMID- 20305476 TI - Key factors contributing to the success of clinician investigators: converting K08 and K23 to R01 awards. PMID- 20305477 TI - Riding the waves: intrinsic theta generation in the hippocampus. PMID- 20305478 TI - Creation and validation of a new animal model of intracranial aneurysms. PMID- 20305479 TI - Forcing tumor stem cells to an end. PMID- 20305480 TI - Intrathecal nucleic acid injections to treat neuropathic pain. PMID- 20305481 TI - Regeneration of neuromuscular synapses: action of microRNA-206. PMID- 20305482 TI - IDH1 and IDH2 mutations in gliomas and the associated induction of hypoxia inducible factor and production of 2-hydroxyglutarate. PMID- 20305483 TI - Thoughts on consciousness. PMID- 20305484 TI - CT alone may be inadequate for detecting occult spinal injuries. PMID- 20305485 TI - A T cell-orchestrated immune response in the adult dorsal spinal cord as a cause of neuropathic pain-like hypersensitivity after peripheral nerve damage: a door to novel therapies? PMID- 20305486 TI - Conflict of interest in peer-reviewed medical journals: the World Association of Medical Editors (WAME) position on a challenging problem. PMID- 20305488 TI - Four-level anterior cervical discectomy and fusion with plate fixation: radiographic and clinical results. AB - OBJECTIVE: Anterior cervical discectomy and fusion with plating is a common procedure performed for cervical spondylosis by spine surgeons. However, data on procedures involving 4 disc spaces are lacking. We report the outcomes of patients who underwent 4-level anterior cervical discectomy and fusion with plating at a single institution. METHODS: Between 1997 and 2006, 34 patients (19 females, 15 males; mean age, 58 years; age range, 38-83 years) underwent 4-level anterior cervical discectomy and fusion with plating based on a surgical database search. Only patients undergoing surgery at 4 contiguous disc levels were included. Data were collected in a retrospective fashion. Patients' demographics, symptoms, neurologic findings, and radiographic findings at admission were recorded. Long-term clinical and radiographic outcomes at last follow-up were analyzed. RESULTS: Twenty-nine patients (85%) underwent anterior cervical discectomy and fusion with plating at C3-C7. Sixteen patients presented with neurologic deficits, of which 14 (88%) improved. None worsened after surgery. Minor complications occurred in 26 patients, including transient dysphagia in 18 (53%) and hoarseness in 3 (9%). Radiographic outcomes were available in 27 patients (median follow-up, 15 months; range, 4-71 months). The overall fusion rate was 92.6%. Stable fibrous nonunions were present in 2 patients; the chance of nonunion was 1.9% per level and 7% per patient. Adjacent-level disease occurred in 2 patients. CONCLUSION: In carefully selected patients, 4-level anterior cervical discectomy and fusion with plating can be associated with high rates of fusion. The technique is safe and effective for managing multilevel cervical spondylotic myelopathy and may obviate the need for circumferential procedures. PMID- 20305489 TI - Exacerbation of perihematomal edema and sterile meningitis with intraventricular administration of tissue plasminogen activator in patients with intracerebral hemorrhage. AB - OBJECTIVE: Intraventricular hemorrhage (IVH) is associated with a poor outcome. External ventricular drainage together with clot lysis through intrathecal tissue plasminogen activator (IT-tPA) has been proposed as a promising therapy. However, recent experimental work has implicated tissue plasminogen activator (tPA) in the pathogenesis of cerebral edema. METHODS: We reviewed the records of all patients with IVH caused by primary supratentorial intracerebral hemorrhage who underwent external ventricular drainage without surgical evacuation between January 2001 and June 2008. Of these 30 patients, we identified 13 who received IT-tPA. The remaining 17 patients served as controls. Hemorrhage, edema volume, and IVH score were determined on admission and by follow-up computed tomographic scans for 96 hours after admission. Discharge outcome was evaluated using the modified Rankin Scale. RESULTS: There were no significant differences between the treatment and controls in terms of age, Glasgow Coma Scale score, Graeb and LeRoux IVH scores, or intracerebral hemorrhage volume on admission. IT-tPA resulted in more rapid clearance of IVH as determined by the 96-hour decrease in both the Graeb IVH score (tPA, 3.00 +/- .55; control, 1.00 +/- 0.57; P = .05) and the LeRoux IVH score (tPA, 6.2 +/- 0.80; control, 2.25 +/- 1.32; P = .05). Patients treated with IT-tPA demonstrated significantly larger peak ratios of edema to intracerebral hemorrhage volume (1.24 +/- 0.14 vs 0.70 +/- 0.08 in controls; P = .002). Additionally, increased rates of sterile meningitis (46% vs 12%; P = .049) and a trend toward shunt dependence (38% vs 6%; P = .06) were observed in the tPA cohort. Nevertheless, no significant differences in outcome at discharge or length of hospital stay were observed between cohorts. CONCLUSION: Although IT tPA hastens the resolution of IVH, it may worsen perihematomal edema formation. Larger prospective studies are required to confirm these findings and to determine whether outcome is adversely affected by IT-tPA administration. PMID- 20305490 TI - Microvascular decompression for tinnitus: significant improvement for tinnitus intensity without improvement for distress. A 4-year limit. AB - OBJECTIVE: Microvascular compressions of the cochlear nerve can lead to tinnitus. The tinnitus initially is related to nonsynchronous signal transmission in the auditory nerve, neurophysiologically characterized by a peak II amplitude decrease. Chronic compression can lead to a focal demyelination, resulting in an increase in Iinterpeak latency I-III with tinnitus and frequency-specific hearing loss as a consequence. Decompressing the cochlear nerve may result in improvement in tinnitus if the auditory nerve is not too damaged for recovery. The aim of the study is to find a cut-off point for this recovery based on clinical data. MATERIALS AND METHODS: Twenty patients undergo a microvascular decompression of the vestibulocochlear nerve for unilateral intractable tinnitus. Pre- and postoperative visual analogue scale for tinnitus intensity and tinnitus questionnaires for tinnitus distress are analyzed before and after microvascular decompression. RESULTS: Of the 20 patients studied, 10 had improvements on their tinnitus visual analogue score intensity postoperatively, 8 were unchanged, and 2 worsened. On the Tinnitus Questionnaire scores, 7 of 13 patients improved and 6 of the 13 patients worsened. If decompression is performed before the end of the 4th year of tinnitus duration, a significant tinnitus intensity improvement can be obtained (P < .05); after 4 years, improvement cannot be obtained (P = .55). However, the tinnitus distress does not seem to decrease significantly. CONCLUSION: Microvascular decompression of the cochlear nerve can improve tinnitus intensity in selected patients if decompression is performed early, before the end of the 4th year. Tinnitus distress does not seem to change. PMID- 20305491 TI - Gamma knife surgery of meningiomas involving the cavernous sinus: long-term follow-up of 100 patients. AB - OBJECTIVE: Resection of meningiomas involving the cavernous sinus often is incomplete and associated with considerable morbidity. As a result, an increasing number of patients with such tumors have been treated with gamma knife surgery (GKS). However, few studies have investigated the long-term outcome for this group of patients. METHODS: 100 patients (23 male/77 female) with meningiomas involving the cavernous sinus received GKS at the Department of Neurosurgery at Haukeland University Hospital, Bergen, Norway, between November 1988 and July 2006. They were followed for a mean of 82.0 (range, 0-243) months. Only 2 patients were lost to long-term follow-up. Sixty patients underwent craniotomy before radiosurgery, whereas radiosurgery was the primary treatment for 40 patients. RESULTS: Tumor growth control was achieved in 84.0% of patients. Twelve patients required re-treatment: craniotomy (7), radiosurgery (1), or both (4). Three out of 5 patients with repeated radiosurgery demonstrated secondary tumor growth control. Excluding atypical meningiomas, the growth control rate was 90.4%. The 1-, 5-, and 10-year actuarial tumor growth control rates are 98.9%, 94.2%, and 91.6%, respectively. Treatment failure was preceded by clinical symptoms in 14 of 15 patients. Most tumor growths appeared within 2.5 years. Only one third grew later (range, 6-20 yr). The complication rate was 6.0%: optic neuropathy (2), pituitary dysfunction (3), worsening of diplopia (1), and radiation edema (1). Mortality was 0. At last follow-up, 88.0% were able to live independent lives. CONCLUSION: GKS gives long-term growth control and has a low complication rate. Most tumor growths manifest within 3 years following treatment. However, some appear late, emphasizing the need for long-term follow up. PMID- 20305492 TI - Direct posterior reduction and fixation for the treatment of basilar invagination with atlantoaxial dislocation. AB - OBJECTIVE: To report the surgical technique and clinical results for the treatment of basilar invagination (BI) with atlantoaxial dislocation (AAD) by direct posterior reduction and fixation using intraoperative distraction between the occiput and C2 pedicle screws. METHODS: From May 2004 to June 2008, 29 patients who had BI with AAD were surgically treated in our department. Pre- and postoperative dynamic cervical x-rays, computed tomographic scans, and 3 dimensional reconstruction views were performed to assess the degree of dislocation. Ventral compression of the cervicomedullary junction was evaluated by magnetic resonance imaging. For all patients, reduction of the AAD was conducted by intraoperative distraction between the occiput and C2 pedicle screws using a direct posterior approach. RESULTS: Follow-up ranged from 6 to 50 months in 28 patients. Clinical symptoms improved in 26 patients (92.9%) and were stable in 2 patients (7.1%) without postoperative deterioration. Radiologically, complete or more than 50% reduction was achieved in 27 of 28 patients (96.4%). In 1 patient, the reduction was less than 50% because the direction of the facets on 1 side of the C1-C2 joint was vertically oriented, instead of horizontal. Overall, good decompression and bone fusion were shown on postoperative magnetic resonance imaging, computed tomography, or x-ray scans for all patients. There was 1 death in the series because of basilar artery thrombosis 1 week after the operation. CONCLUSION: The direct posterior distraction technique between occiput and C2 pedicle screws is an effective, simple, fast, and safe method for the treatment of BI with AAD. Transoral odontoidectomy and cervical traction for the treatment of BI with AAD should be reconsidered. PMID- 20305493 TI - Developing an articular cartilage decellularization process toward facet joint cartilage replacement. AB - OBJECTIVE: The facet joint has been identified as a significant source of morbidity in lower back pain. In general, treatments have focused on reducing the pain associated with facet joint osteoarthritis, and no treatments have targeted the development of a replacement tissue for arthritic facet articular cartilage. Therefore, the objective of this study was to develop a nonimmunogenic decellularized articular cartilage replacement tissue while maintaining functional properties similar to native facet cartilage tissue. METHODS: In vitro testing was performed on bovine articular cartilage explants. The effects of 2% sodium dodecyl sulfate (SDS), a detergent used for cell and nuclear membrane solubilization, on cartilage cellularity, biochemical, and biomechanical properties, were examined. Compressive biomechanical properties were determined using creep indentation, and the tensile biomechanical properties were obtained with uniaxial tensile testing. Biochemical assessment involved determination of the DNA content, glycosaminoglycan (GAG) content, and collagen content. Histological examination included hematoxylin and eosin staining for tissue cellularity, as well as staining for collagen and GAG. RESULTS: Treatment with 2% SDS for 2 hours maintained the compressive and tensile biomechanical properties, as well as the GAG and collagen content while resulting in a decrease in cell nuclei and a 4% decrease in DNA content. Additionally, treatment for 8 hours resulted in complete histological decellularization and a 40% decrease in DNA content while maintaining collagen content and tensile properties. However, a significant decrease in compressive properties and GAG content was observed. Similar results were observed with 4 hours of treatment, although the decrease in DNA content was not as great as with 8 hours of treatment. CONCLUSION: Treatment with 2% SDS for 8 hours resulted in complete histological decellularization with decreased mechanical properties, whereas treatment for 2 hours maintained mechanical properties, but had a minimal effect on DNA content. Therefore, future studies must be performed to optimize a treatment for decellularization while maintaining mechanical properties close to those of facet joint cartilage. This study served as a step in creating a decellularized articular cartilage replacement tissue that could be used as a treatment for facet cartilage osteoarthritis. PMID- 20305494 TI - Platelet-derived growth factor-induced severe and chronic vasoconstriction of cerebral arteries: proposed growth factor explanation of cerebral vasospasm. AB - OBJECTIVE: After subarachnoid hemorrhage (SAH), platelet-derived growth factor-BB (PDGF-BB) is secreted in and around the cerebral arteries. To clarify the role of PDGF-BB in the development of vasospasm after SAH, we determined whether PDGF-BB alone can cause long-lasting vasoconstriction of a severity similar to that of vasospasm. In addition, the anti-vasospastic effect of trapidil, an antagonist of PDGF-BB function, was investigated. METHODS: We infused recombinant PDGF-BB (10 microg/mL saline as the vehicle) (n = 14) into the subarachnoid space of rabbits and analyzed alterations in the caliber of the basilar artery using repeated angiography. To study the role of PDGF-BB on the development of vasospasm, trapidil was administered continuously starting 1 hour after SAH, on day 0 (0.63 1.25 mg/kg /h or vehicle) for 47 hours (n = 24), or after the full development of cerebral vasospasm on day 2 (3.0 mg/kg/h or vehicle) for 0.5 hours (n = 17), and alterations in the caliber of the basilar artery were monitored. RESULTS: PDGF-BB caused long-lasting vasoconstriction, with maximum constriction of 56% (P < .001) of the control value (= 100%) on day 2, resembling vasospasm seen after SAH. Prolonged administration of intravenous trapidil, starting soon after SAH, prevented the development of vasospasm in a dose-dependent manner (P < .05, .01, or .001). Intravenous or intra-arterial administration of trapidil significantly dilated vasospasm (P < .01) on day 2, at least transiently. CONCLUSION: PDGF-BB, a growth factor synthesized in the subarachnoid space after SAH, can cause severe and long-lasting vasoconstriction. Significant prevention and resolution of vasospasm can be achieved by the PDGF-BB antagonist trapidil. We propose that excessive production of PDGF-BB, essentially aiming to repair injured arteries, causes cerebral vasospasm. Although the half-life of trapidil in serum may be shorter than that of PDGFG-BB-derived spasmogenic signaling, trapidil is a candidate drug for constructing a new therapeutic modality for preventing and resolving vasospasm. PMID- 20305495 TI - The brain tumor window model: a combined cranial window and implanted glioma model for evaluating intraoperative contrast agents. AB - OBJECTIVE: Optical contrast agents for brain tumor delineation have been previously evaluated in ex vivo specimens from animals with implanted gliomas and may not reflect the true visual parameters encountered during surgery. This study describes a novel model system designed to evaluate optical contrast agents for tumor delineation in vivo. METHODS: Biparietal craniectomies were performed on 8 week-old Sprague-Dawley rats. 9L glioma cells were injected intraparenchymally. A cover slip was bonded to the cranial defect with cyanoacrylate glue. When the tumor radius reached 1 mm, Coomassie Blue was administered intravenously while the appearance of the cortical surface was recorded. Computerized image analysis of the red/green/blue color components was used to quantify visible differences between tumor and nonneoplastic tissue and to compare delineation in the brain tumor window (BTW) model with the conventional 9L glioma model. RESULTS: The tumor margin in the BTW model was poorly defined before contrast administration but readily apparent after contrast administration. Based on red component intensity, tumor delineation improved 4-fold at 50 minutes after contrast administration in the BTW model (P < .002). The conventional 9L glioma model overestimated the degree of delineation compared with the BTW model at the same dose of Coomassie Blue (P < .03). CONCLUSION: Window placement overlying an implanted glioma is technically possible and well tolerated in the rat. The BTW model is a valid system for evaluating optical contrast agents designed to delineate brain tumor margins. To our knowledge, we have described the first in vivo model system for evaluating optical contrast agents for tumor delineation. PMID- 20305496 TI - Firefly luciferase-based dynamic bioluminescence imaging: a noninvasive technique to assess tumor angiogenesis. AB - OBJECTIVE: Bioluminescence imaging (BLI) is emerging as a cost-effective, high throughput, noninvasive, and sensitive imaging modality to monitor cell growth and trafficking. We describe the use of dynamic BLI as a noninvasive method of assessing vessel permeability during brain tumor growth. METHODS: With the use of stereotactic technique, 10 firefly luciferase-transfected GL26 mouse glioblastoma multiforme cells were injected into the brains of C57BL/6 mice (n = 80). After intraperitoneal injection of D-luciferin (150 mg/kg), serial dynamic BLI was performed at 1-minute intervals (30 seconds exposure) every 2 to 3 days until death of the animals. The maximum intensity was used as an indirect measurement of tumor growth. The adjusted slope of initial intensity (I90/Im) was used as a proxy to monitor the flow rate of blood into the vascular tree. Using a modified Evans blue perfusion protocol, we calculated the relative permeability of the vascular tree at various time points. RESULTS: Daily maximum intensity correlated strongly with tumor volume. At postinjection day 23, histology and BLI demonstrated an exponential growth of the tumor mass. Slopes were calculated to reflect the flow in the vessels feeding the tumor (adjusted slope = I90/Im). The increase in BLI intensity was correlated with a decrease in adjusted slope, reflecting a decrease in the rate of blood flow as tumor volume increased (y = 93.8e-0.49, R2 = 0.63). Examination of calculated slopes revealed a peak in permeability around postinjection day 20 (n = 42, P < .02 by 1-way analysis of variance) and showed a downward trend in relation to both postinjection day and maximum intensity observed; as angiogenesis progressed, tumor vessel caliber increased dramatically, resulting in sluggish but increased flow. This trend was correlated with Evans blue histology, revealing an increase in Evans blue dye uptake into the tumor, as slope calculated by BLI increases. CONCLUSION: Dynamic BLI is a practical, noninvasive technique that can semiquantitatively monitor changes in vascular permeability and therefore facilitate the study of tumor angiogenesis in animal models of disease. PMID- 20305497 TI - The legacy of Johann Friedrich Meckel the Elder (1724-1774): a 4-generation dynasty of anatomists. AB - Few families have had an impact on medicine to equal that of the Meckel family. Johann Friedrich Meckel the Elder is of special interest to the neurosciences, given that his dissertation on the fifth cranial nerve included the first description of the arachnoid space investing the trigeminal nerve into the middle fossa. He was interested in neuroanatomy, along with botany and pathology of the inguinal hernia and the lymphatic system. His mentors included the eminent Albrecht von Haller (1708-1777) and August Buddaeus (1695-1753), and he extended his own influence on the work of Giovanni Morgagni and Alexander Monro II. He spent the latter part of his life in Berlin as professor of anatomy, botany, and obstetrics. His son, Philipp Friedrich Theodor Meckel (1755-1803), was one of the founders of the current collection of anatomic specimens at the University of Halle and provided important groundwork for the practice of obstetrics. Meckel the Elder's grandson, Johann Friedrich Meckel the Younger (1781-1833), was a more prolific investigator and founder of the science of teratology. Many anatomic structures, such as Meckel's diverticulum, bear his name, and he vastly expanded the university's anatomic collection. August Albrecht Meckel (1789-1829), Meckel the Younger's brother, practiced legal medicine and investigated avian anatomy but died prematurely from tuberculosis. August's son, Johann Heinrich Meckel (1821-1856), took the instructor's position in pathologic anatomy at the University of Berlin that his great-grandfather had held at the Charite. After his untimely death from pulmonary disease, his position was filled by Rudolf Virchow. The history of this family is discussed in detail. PMID- 20305498 TI - In vivo visualization of cranial nerve pathways in humans using diffusion-based tractography. AB - OBJECTIVE: Diffusion-based tractography has emerged as a powerful technique for 3 dimensional tract reconstruction and imaging of white matter fibers; however, tractography of the cranial nerves has not been well studied. In particular, the feasibility of tractography of the individual cranial nerves has not been previously assessed. METHODS: 3-Tesla magnetic resonance imaging scans, including anatomic magnetic resonance images and diffusion tensor images, were used for this study. Tractography of the cranial nerves was performed using 3D Slicer software. The reconstructed 3-dimensional tracts were overlaid onto anatomic images for determination of location and course of intracranial fibers. RESULTS: Detailed tractography of the cranial nerves was obtained, although not all cranial nerves were imaged with similar anatomic fidelity. Some tracts were imaged in great detail (cranial nerves II, III, and V). Tractography of the optic apparatus allowed tracing from the optic nerve to the occipital lobe, including Meyer's loop. Trigeminal tractography allowed visualization of the gasserian ganglion as well as postganglionic fibers. Tractography of cranial nerve III shows the course of the fibers through the midbrain. Lower cranial nerves (cranial nerves IX, XI, and XII) could not be imaged well. CONCLUSION: Tractography of the cranial nerves is feasible, although technical improvements are necessary to improve the tract reconstruction of the lower cranial nerves. Detailed assessment of anatomy and the ability of overlaying the tracts onto anatomic magnetic resonance imaging scans is essential, particularly in the posterior fossa, to ensure that the tracts have been reconstructed with anatomic fidelity. PMID- 20305499 TI - Extensions of the sphenoid sinus: a new classification. AB - OBJECTIVE: The transsphenoidal approach has been extended in recent years from tumors of the sellar region to lesions involving other areas bordering the sphenoid sinus including the cavernous sinus, Meckel's cave, middle cranial fossa, planum sphenoidal, suprasellar region, and clivus. The goal of this study was to examine various pneumatized extensions of the sphenoid sinus that may facilitate extended approaches directed through the sinus. METHODS: The sphenoid sinus and its surrounding structures were examined in 18 cadaver heads, and the results were correlated with the findings from 100 computed tomography images of the sinus. The sellar type of the sphenoid sinus in which the pneumatization extended beyond the anterior sellar wall was further classified according to the various extensions of the sinus. RESULTS: The sellar type of the sphenoid sinus was classified into the following 6 basic types based on the direction of pneumatization: sphenoid body, lateral, clival, lesser wing, anterior, and combined. The recesses and prominences, formed by pneumatization of the sinus, act as "windows" opening from the sinus in different areas of the cranial base and may facilitate minimally invasive access to lesions in the corresponding areas. CONCLUSION: The variations in the extensions of pneumatization of the sphenoid sinus may facilitate entry into areas bordering the sphenoid sinus and play a role in the selection of a surgical approach to lesions bordering the sinus. PMID- 20305500 TI - Endoscopic decompression of the ulnar nerve at the elbow. AB - OBJECTIVE: Recently, several studies suggested that simple decompression is as effective as anterior transposition in ulnar nerve entrapment syndrome. Simple decompression might be performed with minimally invasive techniques. The authors present their technique and results with endoscopic decompression in ulnar nerve entrapment syndrome. MATERIAL AND METHODS: Between January 2005 and March 2008, 24 patients (mean age, 45.5 years; range, 26-67 years) underwent surgery for 26 ulnar nerve entrapment syndromes (2 bilateral). All patients presented with typical clinical signs and neurophysiologic studies. RESULTS: Intraoperatively, the ulnar nerve was localized directly at the sulcus, and subsequently under endoscopic view, the decompression was completed approximately 10 cm proximal as well as distal. In 26 cases, a significant compression of the nerve was found directly at and distal to the sulcus. In 1 case, a subluxation of the nerve was observed, the endoscopic technique was abandoned, and open anterior submuscular transposition followed. The procedure was successful in 19 of 22 cases (86%). Neither intraoperative nor postoperative complications were observed. Nevertheless, the identification of the nerve directly at the sulcus, where severe nerve compression was often found, seemed to be difficult and potentially risky, particularly in obese patients. CONCLUSION: The endoscopic technique for ulnar nerve entrapment syndrome seems to be safe and effective. However, particularly in patients with a thick subcutaneous fat layer, identification of the nerve at the sulcus is difficult and possible more risky than in open simple decompression. A randomized prospective study should be performed to further evaluate the value of this new technique in the treatment of ulnar nerve entrapment syndrome. PMID- 20305501 TI - Statistics for oculoplastic surgeons. PMID- 20305502 TI - Levator excursion and its relationship to lid lag in thyroid eye disease. PMID- 20305503 TI - Lateral bilobed flap for anterior lamellar eyelid reconstruction. AB - PURPOSE: To describe anterior lamellar lower eyelid reconstruction with a laterally based bilobed flap. METHODS: A retrospective study of 11 patients who underwent lower eyelid anterior lamellar reconstruction with or without posterior lamellar grafting following tumor excision within a 2-year timeframe were reviewed. RESULTS: Seven women and 4 men (age range, 46.8-95.3 years; mean age, 74.1 years) were included in the study. Nine patients had basal cell carcinoma, and 2 patients had squamous cell carcinoma. The mean defect size was 5.2 cm. Four patients who underwent concomitant posterior lamellae reconstruction were included. Follow-up averaged 10.2 months. No infections, flap failure, or lagophthalmos were found postoperatively. One patient developed medial ectropion. CONCLUSION: A laterally based bilobed flap should be thought of as an effective choice for lower eyelid anterior lamellar reconstruction. PMID- 20305505 TI - Ultrasonic bone removal versus high-speed burring for lateral orbital decompression: comparison of surgical outcomes for the treatment of thyroid eye disease. AB - PURPOSE: To evaluate the efficacy of ultrasonic bone removal during lateral orbital decompression for thyroid eye disease. METHODS: Retrospective, comparative, interventional case series of lateral orbital decompressions performed by the senior author for thyroid eye disease between July 2005 and July 2008. Patients were excluded if they had other coexisting orbital conditions or concurrent decompression of other orbital walls. Primary outcome measures included visual acuity, proptosis, lagophthalmos, eyelid retraction, and exposure keratopathy. RESULTS: Thirty-six consecutive lateral orbital decompressions performed by the senior author were reviewed. The Sonopet Omni ultrasonic surgical aspirator was used to remove the lateral wall in 18 cases, and a high speed drill with a cutting burr was used in the other 18 cases. There was no significant difference between the groups in postoperative visual acuity, proptosis reduction, lagophthalmos, eyelid retraction, exposure keratopathy, or surgical complications. The average reduction in proptosis was 3.9 mm (range, 1 6.5 mm) in the Sonopet group and 4.0 mm (range, 1-6 mm) in the drill group (p = 0.86). In our series, the average surgical case time was slightly shorter in the Sonopet group than in the drill group (104 vs. 118 minutes, p = 0.032). CONCLUSIONS: Ultrasonic bone removal is a safe and effective alternative to high speed burring during lateral orbital decompression for thyroid eye disease. PMID- 20305504 TI - The bioceramic implant: evaluation of implant exposures in 419 implants. AB - PURPOSE: To compare the rate of exposure in the immediate 3-month postoperative follow-up period with the rate of exposure after the immediate postoperative period in 419 anophthalmic patients with a bioceramic (aluminum oxide) orbital implant. METHODS: This is a retrospective, clinical case series of 419 patients who received a bioceramic orbital implant. All patients who presented to five oculofacial surgeons (D.J., S.G., J.D., S.K., L.M.) from January 1, 2000, to June 1, 2007, who received a bioceramic orbital implant and had a minimum of 3 months of follow-up were included in this study. The authors analyzed age, gender, type of surgery, implant size, peg system, follow-up duration, time of pegging, and problems encountered. The data from the patients with greater than 3 months of follow-up with exposure of the bioceramic implant are detailed in this report. RESULTS: There were 353 patients followed for 3 to 96 months with an average of 30 months of follow-up (median 23 months). Implant exposure occurred in 32/353 bioceramic implants (9.1%). Six of the 32 (19%) exposures occurred during the 90 day postoperative period (average 2.1 months). Twenty-six (81%) exposures occurred outside of the 90-day postoperative period (average 27.5 months, range 4 82 months). CONCLUSIONS: Implant exposures can occur anytime postimplant placement. This review discovered an implant exposure rate of 9.1%, with the majority of the exposures occurring after the postoperative follow-up period. Patients with porous orbital implants should be followed on a long-term basis to detect this complication. PMID- 20305506 TI - Cutaneous melanoma metastatic to the eyelid and periocular skin. AB - PURPOSE: To report the clinical and histopathologic features in 6 patients with cutaneous melanoma metastatic to the eyelid and periocular skin. METHODS: Clinical records and radiographic features of all consecutive patients treated by the principal investigator between January 2005 and October 2007 with the diagnosis of cutaneous melanoma metastatic to the eyelid and periocular skin. RESULTS: Six patients ranged in age from 26 to 84 years old (median, 55 years). Five patients had their metastatic lesion in the upper eyelid and 1 in the lower eyelid. The mean survival after the diagnosis of melanoma metastatic to the eyelid was 5.3 months. All patients had metastases at other sites detected prior to the diagnosis of the eyelid metastasis. The mean interval from initial primary tumor diagnosis to metastasis to the eyelid was 121 months. In all 6 patients, palliative surgical resection of the metastatic eyelid lesions was carried out. CONCLUSIONS: Melanoma metastatic to the eyelid is not uncommon in advanced stage cutaneous melanoma. Palliative surgical management of these metastatic lesions should be considered to improve the patient's quality of life. PMID- 20305507 TI - Cosmetic surgery survey of american society of oculoplastic and reconstructive surgery members and a 6-year comparison. AB - PURPOSE: To examine the current cosmetic practices of American Society of Oculoplastic and Reconstructive Surgery members using a survey and compare those results with a similar survey that was performed 6 years prior, and to determine the types and breadth of cosmetic procedures that are currently performed within the field of ophthalmic plastic and reconstructive surgery. METHODS: A 49 question survey was sent to members of American Society of Oculoplastic and Reconstructive Surgery by post mail and/or electronic mail in 2007. The questions covered surgeon demographics, cosmetic practice design, and preferences for aesthetic procedures and commercial equipment and products. Frequencies and percentages of responses were obtained for each question individually. Responses to similar questions in a 2001 survey were compared with those in the current survey. RESULTS: Two hundred fifty-seven members of 488 responded (53%). Eighty two percent of respondents (208 of 253) performed some type of cosmetic procedure. Fifty-five percent of respondents reported that less than 25% of their practice consisted of cosmetic procedures and services. Thirty-one percent of respondents reported that 25% to 75% of their practice was cosmetic. CONCLUSIONS: A slightly higher percentage of respondents reported that more of their practice consisted of cosmetic procedures and services compared with 6 years ago; however, the difference did not reach statistical significance (p = 0.895). A lower percentage of respondents injected Botox cosmetic (p = 0.02), offered ablative laser skin resurfacing (p < 0.001), and performed rhytidectomy (p < 0.001) in 2007 compared with 2001. PMID- 20305508 TI - Imiquimod 5% cream for the treatment of periocular Basal cell carcinoma. AB - PURPOSE: The objective of this pilot study was to evaluate the efficacy and safety of 5% imiquimod cream in the treatment of periocular basal cell carcinoma (BCC) through the analysis of a case series. METHODS: Eight subjects with primary nodular BCC of the eyelid were recruited. Treatment lasted 10 to 16 weeks. The average follow-up time was 11.7 months. RESULTS: Of a total of 10 lesions, 80% resolved clinically and histologically and have remained asymptomatic since. CONCLUSION: Imiquimod cream 5% was shown to be an attractive alternative to surgical treatment of periocular BCC. Future studies with larger samples and longer follow-up periods are expected to provide more accurate information on the efficacy and safety of the drug. PMID- 20305509 TI - Does the length of intubation affect the success of treatment for congenital nasolacrimal duct obstruction? AB - PURPOSE: To compare success rates of intubation for 2 versus 5 months in congenital nasolacrimal duct obstruction in children between 15 and 30 months of age. METHODS: This prospective, randomized study evaluated drainage function in 145 eyes of children aged between 15 and 30 months and treated for congenital nasolacrimal duct obstruction using silicone stents with the fluorescein dye disappearance test. The tubes were removed 2 months (group I, 48 eyes) and 5 months (group II, 47 eyes) after stent placement. Thereafter, the children were followed for 6 months after tube removal. Fifty eyes were excluded from the study because of incomplete follow-up. RESULTS: The full resolution of symptoms (fluorescein test 0-1) was 33 of 48 in group I and 33 of 47 in group II at the time of tube removal (2 vs. 5 months). Six months after tube removal, the success rate was 43 of 48 (89.6%) in group I and 43 of 47 (91.5%) in group II. After the stents were removed, no relapses were observed in children having a fluorescein test 0-1 with the tubes remaining in the lacrimal system. CONCLUSIONS: The effects of intubation for 2 versus 5 months on the function of the nasolacrimal duct during and after intubation in children between 15 and 30 months of age are comparable. The fluorescein dye disappearance test is the test of choice for monitoring lacrimal drainage function. PMID- 20305510 TI - Orbital involvement in craniofacial brown tumors. AB - PURPOSE: To describe the clinical and radiologic features of orbital involvement in craniofacial brown tumors and to compare the rate of brown tumors in primary and secondary hyperparathyroidism. METHODS: A retrospective hospital-based study of 115 patients with chronic kidney disease and secondary hyperparathyroidism and 34 with primary hyperparathyroidism was conducted. Laboratory results such as serum levels of alkaline phosphatase, calcium, phosphorus, and parathyroid hormone were recorded. Demographic data (age, sex, duration of disease) and image findings (bone scan scintigraphy, skull and long bone x-rays, CT) were also obtained. The main outcome measures were analysis of clinical, biochemical, and radiologic findings of all patients. RESULTS: Of the 115 patients with chronic kidney disease, 10 (8.7%) had brown tumors in different bones of the skeleton. Five patients had lesions in the craniofacial bones. The maxilla, mandible, maxillary sinus, and nasal cavity were the most affected sites. The orbit was involved in 2 patients with lesions arising in the maxillary and ethmoid sinuses. One patient had facial leontiasis. All patients with brown tumors had extremely high levels of parathyroid hormone (>1,000 pg/ml, normal values 10-69 pg/ml) and alkaline phosphatase (>400 U/l, normal values 65-300 U/l). The mean serum levels of phosphorus and calcium were not abnormal among the patients with brown tumors. Age and time of renal failure were similar for patients with and without brown tumors. Among the patients with primary hyperparathyroidism, only 2 (5.8%) had brown tumors, and in just 1, the lesion was localized in the craniofacial skeleton. A 2-tailed Z test applied to compare the proportion of occurrence of brown tumors in the 2 groups revealed that the difference at the 90% of confidence level was not significant. CONCLUSIONS: Brown tumors are equally found in secondary and primary hyperparathyroidism. Craniofacial brown tumors involve the orbit, usually because of the osteodystrophy process that involves the maxilla and paranasal sinuses. The lesions do not necessarily need to be excised and may regress spontaneously after the control of hyperparathyroidism. PMID- 20305511 TI - Eyelash resection procedure for severe, recurrent, or segmental cicatricial entropion. AB - PURPOSE: To study the safety, efficacy, and cosmetic outcome of the eyelash resection procedure for treatment of severe, recurrent, or segmental cicatricial entropion. METHODS: Retrospective consecutive case series of patients with severe, recurrent, or segmental cicatricial entropion treated with eyelash resection at the Moran Eye Center and the University of Vermont. Investigators performed chart reviews of these patients and evaluated effectiveness of the treatment and outcome data, including age, gender, diagnoses, method of repair, recurrence of trichiasis, and cosmetic satisfaction. There were no exclusionary characteristics specified in the study. RESULTS: A total of 26 eyelids were operated on in 5 male and 11 female patients. The mean age was 74 years, with the following diagnoses: idiopathic (6), ocular cicatricial pemphigoid (2), postoperative (2), ocular pseudopemphigoid (drug related) (1), graft-versus-host disease (1), Stevens-Johnson syndrome (1), trachoma (1), linear IgA bullous dermatosis (1), and trauma (1). Mean postoperative follow-up was 13 months. The functional success rate was 90.5%, and the cosmetic success rate was 100%. CONCLUSION: The eyelash resection procedure is a safe, effective, and cosmetically acceptable procedure for treatment of severe, recurrent, or segmental cicatricial entropion. PMID- 20305512 TI - Subconjunctival "ring" recurrence of Basal cell carcinoma of the globe. AB - Basal cell carcinoma is the most common indication for orbital exenteration. The recurrence rate of BCC removed with microscopically controlled histology sections is up to 6%. The authors describe the recurrence of a lower eyelid BCC resected with microscopic control that did not manifest itself until 15 years later as a subconjunctival lesion, encircling the globe, and without apparent skin involvement. BCC can present in any manner following surgery, and therefore, judicious follow-up is necessary even after microscopically controlled resection. PMID- 20305513 TI - Spontaneous dural cavernous fistula in infancy. AB - A 4-month-old boy presented with the sudden onset of proptosis and dilated episcleral veins. CT revealed an enlarged superior ophthalmic vein and diffusely thickened extraocular muscles. MRI and angiography confirmed a dural middle meningeal--cavernous sinus fistula. Embolization was performed leading to successful resolution of the patient's signs and symptoms. Spontaneous atraumatic arteriovenous cavernous fistulae in infancy are extremely rare, but should be included in the differential diagnosis of infants with orbital congestion. Appropriate treatment leads to prevention of amblyopia, glaucoma, and anisometropia. PMID- 20305514 TI - Metaplastic bone formation in the orbit. AB - Osseous or cartilaginous metaplasia in the orbit are both rare phenomena. The authors describe a unique case of combined primary orbital osseous and cartilaginous metaplasia presenting with orbital pain and ocular dysmotility and discuss the radiologic, histopathologic, and clinical features. This entity should be considered in the differential diagnosis of an orbital mass showing similar radiographic features of calcification. PMID- 20305515 TI - Compressive effects of intravascular papillary endothelial hyperplasia. AB - A 45-year-old woman presented with an 8-month history of a firm mass over the right superonasal orbital rim, followed by an episode of hemorrhage and anesthesia 5 months later. Clinical history and CT were suggestive of a venous malformation with phleboliths. Excision biopsy was performed. Histopathology revealed intravascular papillary endothelial hyperplasia with fibrotic-calcific changes. Hypoesthesia in the supra-orbital region persisted postoperatively. Although a benign lesion, intravascular papillary endothelial hyperplasia should be considered a differential diagnosis of a vascular lesion with compressive effects. PMID- 20305516 TI - Management of facial disfigurement in orbitotemporal neurofibromatosis. AB - A 19-year-old woman with type I neurofibromatosis requested reconstruction of her severe facial disfigurement caused by the plexiform neurofibroma of the right upper eyelid. Previously, she had glaucoma surgery for buphthalmus and enucleation with dermis fat transplantation. She was unable to wear prosthesis in the last year. Transverse palpebral resection of the lesion, lateral canthal reconstruction, and frontal sling ptosis surgery were performed at the same session. Postoperatively, the cosmetic appearance of the patient was markedly improved. No complication or progression was observed during 2 years follow-up. We believe that an individual-based surgical plan may give acceptable results in these challenging cases. PMID- 20305517 TI - IgA orbital plasmacytoma in multiple myeloma. AB - The authors report a case of orbital plasmacytoma in a 48-year-old man with known multiple myeloma. He presented with proptosis, diplopia, and decreased vision of the left eye for several weeks. He had been previously treated for IgA lambda multiple myeloma with chemotherapy, radiation, and autologous stem cell transplant. After a left orbitotomy, flow cytometry revealed a tumor rich in plasma cells expressing CD138 with equivocal lambda light chain expression. The patient underwent orbital radiation, with improvement of vision and disc edema OS. The patient is currently undergoing salvage chemotherapy for relapse of multiple myeloma. This is the third reported case of IgA myeloma involving the orbit. PMID- 20305518 TI - Recurrent Rhodococcus gordoniae eyelid infection after combined septoplasty and blepharoplasty. AB - Rhodococcus species are rare human pathogens. Most cases of human infection have involved Rhodococcus equi, a natural zoonotic pathogen causing pneumonia in young foals. The human population at risk mainly includes immunocompromised patients. Infection of immunocompetent hosts has been rare, with less than 30 reported cases in the literature. The authors report a first case of recurrent Rhodococcus gordoniae granulomatous lower eyelid infection that occurred after an immunocompetent 44-year-old woman underwent a combined intranasal and lower blepharoplasty procedure. A literature search revealed only 10 reported cases of non-R. equi rhodococcal infections, most involving traumatic inoculation; 5 of these cases involved the eye and ocular adnexa. To the author's knowledge, this is the first case report of a non-R. equi rhodococcal infection of the eyelids. Identification of Rhodococcus by most laboratories is difficult, and in this case, 2 of 3 cultures were misidentified prior to definitive testing at a specialized laboratory. Multidrug resistance is also a concern, and the treatment course could be long and difficult. PMID- 20305519 TI - Myxofibrosarcoma of the orbit: a clinicopathologic case report. AB - A 27-year-old woman developed a rapidly progressive left orbital tumor that extended in the cranial fossa. MRI revealed a heterogenous enhancing lesion confined to the left frontal bone and superior orbit. An incisional biopsy was performed, and histopathologic examination of the specimen showed findings diagnostic of a high-grade myxofibrosarcoma. Complete excision with postoperative adjuvant radiation therapy and chemotherapy was performed, and the patient had no evidence of tumor recurrence within 6 months' follow-up. Myxofibrosarcoma is a fibroblast-derived soft tissue neoplasm with up to a 60% local recurrence rate, and metastasis may be associated with intermediate to high-grade tumors. PMID- 20305520 TI - Conservative treatment of adenoid cystic carcinoma with plaque radiotherapy: a case report. AB - Adenoid cystic carcinoma is a rare but aggressive malignant tumor of the lacrimal gland. Mortality rates have been found to be quite high (>50%). This has led to the traditional method of treatment with radical surgery including orbital exenteration and bone resection, followed by external beam radiotherapy to the orbital bed. Despite this aggressive treatment strategy, mortality rates still remain high with only a few reported cases with long-term survival. Recently, several cases of successful treatment of adenoid cystic carcinoma with plaque radiotherapy have been documented. These may show promise of a conservative treatment strategy in selected cases. The authors present a functionally monocular patient with a well-circumscribed adenoid cystic carcinoma that was treated with local excision of the tumor with reverse plaque brachytherapy "boost" to the lacrimal tumor bed followed by a lower dose of radiotherapy to the orbit. The patient is alive and without local recurrence at nearly 4 years. PMID- 20305521 TI - Extensive juvenile xanthogranuloma involving the orbit, sinuses, brain, and subtemporal fossa in a newborn. AB - A 6-week-old-boy presented with a 3-week history of right axial proptosis. Vision, motility, anterior segment, and fundus examinations were normal in both eyes. Imaging revealed a multicystic right orbital lesion with extensive involvement of the infratemporal fossa and paranasal sinuses with intracranial extension. Systemic workup was negative, and he showed no functional deficits. Histopathology revealed a tumor rich in histiocytes, and immunohistochemistry indicated a juvenile xanthogranuloma. He did well with observation, and the tumor partially involuted after 18 months of follow-up. PMID- 20305522 TI - Primary adenoid cystic carcinoma of the eyelid. AB - Adenoid cystic carcinoma is a rare epithelial malignancy, which tends to grow slowly. It is an intractable neoplasm due to its ability to invade perineural spaces. A 59-year-old female presented with a gradually increasing mass in the right lower eyelid. An excisional biopsy with wide margins revealed a diagnosis of primary adenoid cystic carcinoma of eyelid skin with perineural invasion. Although a rare neoplasm, primary adenoid cystic carcinoma of eyelid skin should be included in the differential diagnosis of eyelid tumors. PMID- 20305523 TI - Endoscopic removal of nasoglabellar dermoid cysts. AB - Dermoid cysts are common tumors resulting from entrapped ectodermal elements at fetal suture lines. Management is conceptually straightforward, with surgical excision of the mass in its entirety without rupture. The conspicuous location and potential scarring from direct excision can be objectionable, particularly in children. The authors describe 2 cases using a hidden hairline incision and an endoscopic approach to remove dermoid cysts in the nasoglabellar region. PMID- 20305525 TI - Re: "Long-term success rate of perforated punctal plugs in the management of acquired punctal stenosis". PMID- 20305526 TI - Low-cost endonasal digital photography. PMID- 20305528 TI - Re: "The levator aponeurosis exposed". PMID- 20305529 TI - Steri-strip-assisted temporary tarsorrhaphy, an aid to the lone surgeon. PMID- 20305530 TI - Expanding the phenotype of a neurofibromatosis type 1-like syndrome: a patient with SPRED1 mutation and orbital manifestations: retraction. PMID- 20305531 TI - Commentary: dinosaurs fated for extinction? Health care delivery at academic health centers. AB - Health care delivery at academic health centers (AHCs) can be viewed as dinosaur like. Both are large and complex entities that consume many resources and are slow to adapt to competitive predatory forces. The potential for severe climate shifts, with changes in payer mix, competition from the private sector, and health care reform all occurring in the current health care system, could precipitate either the beginning of extinction for the AHC dinosaur or, hopefully, stimulate its evolution and development into a new model of health care delivery.Given the importance of clinical revenue to the entirety of the AHC enterprise, there is incentive for AHCs to maintain and indeed expand their clinical care delivery mechanisms. Yet, AHCs are institutions of investigation and inquiry. New models of care delivery and their impact on the current clinical care system must be developed through local demonstration projects and experimental clinical models. These models must be studied, and the findings should be shared with the community.The authors argue that this course of action will be challenging because traditional workflows must be restricted to improve care coordination and a changing workforce demographic. It will also require thoughtful approaches to reward innovative clinical work and new directions in strategic management by institution leaders. This commentary outlines recommendations to stave off extinction and enhance the next generation of clinical care delivery at AHCs. PMID- 20305532 TI - Measuring the intensity of resident supervision in the department of veterans affairs: the resident supervision index. AB - PURPOSE: To develop a survey instrument designed to quantify supervision by attending physicians in nonprocedural care and to assess the instrument's feasibility and reliability. METHOD: In 2008, the Department of Veterans Affairs (VA) Office of Academic Affiliations convened an expert panel to adopt a working definition of attending supervision in nonprocedural patient care and to construct a survey to quantify it. Feasibility was field-tested on residents and their supervising attending physicians at primary care internal medicine clinics at the VA Loma Linda Healthcare System in their encounters with randomly selected outpatients diagnosed with either major depressive disorder or diabetes. The authors assessed both interrater concurrent reliability and test-retest reliability. RESULTS: The expert panel adopted the VA's definition of resident supervision and developed the Resident Supervision Index (RSI) to measure supervision in terms of residents' case understanding, attending physicians' contributions to patient care through feedback to the resident, and attending physicians' time (minutes). The RSI was field-tested on 60 residents and 37 attending physicians for 148 supervision episodes from 143 patient encounters. Consent rates were 94% for residents and 97% for attending physicians; test retest reliability intraclass correlations (ICCs) were 0.93 and 0.88, respectively. Concurrent reliability between residents' and attending physicians' reported time was an ICC of 0.69. CONCLUSIONS: The RSI is a feasible and reliable measure of resident supervision that is intended for research studies in graduate medical education focusing on education outcomes, as well as studies assessing quality of care, patient health outcomes, care costs, and clinical workload. PMID- 20305533 TI - A follicular dendritic cell sarcoma of the mediastinum with immature T cells and association with myasthenia gravis. AB - Follicular dendritic cell (FDC) sarcoma is a very rare neoplasm showing morphologic and phenotypic features of FDCs. It occurs primarily in lymph nodes but also in extranodal sites. So far, there have been no reports on FDC sarcoma associated with myasthenia gravis. In the following we will present a case of an FDC tumor of the mediastinum associated with paraneoplastic myasthenia gravis in a 39-year-old man. The tumor contained a major proportion of immature T cells, which may be connected to this patient's very unusual clinical presentation with autoimmune phenomena. Extranodal FDC sarcomas still seem hardly noticed, and their clinical and pathologic characteristics remain to be better defined. PMID- 20305534 TI - Cellular angiofibroma with atypia or sarcomatous transformation: clinicopathologic analysis of 13 cases. AB - Cellular angiofibroma is a mesenchymal neoplasm that is characterized by a bland spindle cell component, morphologically reminiscent of spindle cell lipoma, and thick-walled vessels. The tumor occurs equally in men and women and usually arises in the inguino-scrotal or vulvovaginal regions. An earlier study of 51 cases from our group showed that the tumor follows a benign course without any tendency for recurrence. In 1 case, an intralesional microscopic nodule of pleomorphic liposarcoma was observed. The biologic significance of atypia or sarcomatous transformation in cellular angiofibroma remains uncertain. In this study, we characterized clinicopathologic features in 13 cases of cellular angiofibroma with morphologic atypia or sarcomatous transformation. Thirteen cases with atypia or sarcomatous transformation among 154 usual cellular angiofibromas identified between 1993 and 2009 were retrieved from consultation files. There were 12 females and 1 male ranging in age from 39 to 71 years (median age, 46 y). Tumor size ranged from 1.2 to 7.5 cm. In 11 cases, the tumors occurred in the vulva. One case each occurred in the paratesticular and hip regions. Most tumors were located in subcutaneous tissue. There were 4 cases of cellular angiofibroma with atypia. Three showed severely atypical cells as scattered foci within the cellular angiofibroma. One case showed a discrete nodule of atypical cells. There were 9 cases of cellular angiofibroma with morphologic features of sarcomatous transformation. In each case, abrupt transition to a discrete sarcomatous component was seen. Of these 9 cases, the sarcomatous component in 2 cases showed features of pleomorphic liposarcoma with multivacuolated lipoblasts readily identified. Three of these 9 cases showed discrete nodule(s) closely resembling atypical lipomatous tumor within usual cellular angiofibroma. In the remaining 4 cases, the sarcomatous component was composed of pleomorphic spindle cells arranged in various patterns. By immunohistochemistry, atypical cells and sarcomatous areas showed either multifocal or more diffuse p16 expression compared with either scattered or negative expression in the conventional cellular angiofibroma. The 3 cases with atypical lipomatous tumor-like areas were negative for MDM-2 and CDK4. Follow-up information was available for 7 patients (range from 2 to 75 mo; median: 14 mo). Six patients did not develop recurrence or metastasis. One patient died of metastatic carcinoma of unknown primary site 27 months after the diagnosis of cellular angiofibroma with sarcomatous transformation. Cellular angiofibroma with atypia or morphologic sarcomatous transformation occurs predominantly in the subcutaneous tissue of the vulva and, as yet, shows no evident tendency to recur based on limited clinical follow-up available for 7 cases. The sarcomatous component can show variable features including atypical lipomatous tumor, pleomorphic liposarcoma, and pleomorphic sarcoma NOS. Overexpression of p16 in the atypical cells and sarcomatous component suggests a possible underlying molecular mechanism. PMID- 20305535 TI - Renal cell neoplasms of oncocytosis have distinct morphologic, immunohistochemical, and cytogenetic profiles. AB - This study was undertaken to elucidate the genetic patterns of the renal cell neoplasms of oncocytosis and to compare them with those found in cases with multiple oncocytomas. Three cases of renal oncocytosis and 6 cases of multiple oncocytomas were analyzed. Fluorescence in situ hybridization analysis was performed with centromeric probes for chromosomes 1, 2, 6, 10, and 17 that are typically lost in chromophobe renal cell carcinoma but not in oncocytoma. Immunohistochemistry for cytokeratin 7, parvalbumin, and S100A1 was performed in all cases. Eleven tumors were present in the 3 kidneys with oncocytosis. One of these was a classic chromophobe renal cell carcinoma. In the other 10, none showed any chromosomal losses, whereas 3 showed gains of all 5 chromosomes and 1 had gains of chromosomes 2 and 10. The chromophobe renal cell carcinoma showed losses of chromosome 1, 6, 10, and 17. Twelve of 14 tumors from the patients with multiple oncocytomas showed no loss of any of the chromosomes 1, 2, 6, 10, or 17 and 2 had loss of chromosome 1. All the tumors from kidneys with renal oncocytosis showed strong parvalbumin immunoreactivity, whereas cytokeratin 7 and S100A1 expression were variable. In summary, the renal cell neoplasms of oncocytosis seem to have distinct morphologic, immunohistochemical, and cytogenetic profiles and likely are a distinct entity, not closely related to oncocytoma or chromophobe renal cell carcinoma. PMID- 20305536 TI - Myxoid cystitis with "chordoid" lymphocytes: another mimic of invasive urothelial carcinoma. AB - Invasive urothelial carcinoma is characterized by a number of histologic variants that can sometimes lead to diagnostic difficulty. In addition to those described by the World Health Organization, 2 additional variants have recently been described, invasive urothelial carcinoma with chordoid features and urothelial carcinoma with abundant myxoid stroma, both being characterized by the presence of a prominent myxoid stroma. This report describes a peculiar type of cystitis that closely mimicked myxoid urothelial carcinoma. A transurethral resection specimen from a 73-year-old woman with an earlier diagnosis of invasive urothelial carcinoma focally displayed rounded, epithelioid cells arranged in a corded manner and separated by myxoid stroma; this was originally misinterpreted as recurrent invasive carcinoma. A review of the case with immunohistochemical studies showed the component cells to be polyclonal B-lymphocytes, based upon which the diagnosis of malignancy was reversed. This peculiar form of cystitis, herein termed myxoid cystitis with "chordoid" lymphocytes, has not been described earlier and should be considered among the mimics of invasive urothelial carcinoma, especially those with a myxoid stroma. PMID- 20305537 TI - KRAS mutations in traditional serrated adenomas from Korea herald an aggressive phenotype. AB - The pathogenesis and risk of malignancy of traditional serrated adenomas (TSAs) are unclear. In North America, TSAs are relatively uncommon, occur mainly in the left colon, and in some studies, have not been shown to have a strong association with hyperplastic polyp (HPP) or sessile polyp adenoma (SSA) precursor lesions. In the Far East, and particularly in Korea, TSAs are more common and occur both in the left and right colon. However, the pathogenesis of TSAs in Korean patients, and the similarity to those that occur in North America, have never been evaluated. The purpose of this study was to determine the frequency and type of precursor lesion in TSAs, and to determine the molecular profile according to the grade of histologic dysplasia and/or cancer and anatomic location of the colon in a cohort of Korean patients. One hundred and twelve TSAs were evaluated pathologically and categorized according to the grade of dysplasia (either low or high grade) and the presence or absence of adenocarcinoma. TSAs were also separated into those with serrated versus conventional adenomatous dysplasia. As controls 35 conventional adenomas were evaluated, 14 of which had adenocarcinoma. All lesions were evaluated for the presence and type of precursor lesions and for KRAS and BRAF mutations and methylation of MGMT, hMLH1, and APC. A nondysplastic precursor lesion (HPP or SSA) was identified in 35 TSAs (31.3%). TSAs with a precursor lesion were more commonly found in the right colon compared with the left colon (P=0.03). Mutations of KRAS and BRAF and methylation of MGMT, hMLH1, and APC were present in 29%, 55%, 63%, 56%, and 37% of TSAs, respectively. TSAs with high-grade dysplasia and intramucosal adenocarcinoma showed a significantly higher frequency of KRAS mutation and MGMT methylation, and a significantly lower frequency of BRAF mutations, compared with TSAs with low-grade dysplasia (P<0.05). KRAS mutations were more prevalent in TSAs from the left colon and correlated significantly with higher grades of dysplasia. In a subgroup of TSAs in which both the precursor and neoplastic components were evaluated, a similar molecular profile was shown in both types of epithelium. Our results suggest that up to one-third of TSAs show a histologically identifiable nondysplastic HPP or SSA precursor lesion, particularly in lesions from the right colon. The development of KRAS mutations and methylation of MGMT may herald the onset of an aggressive phenotype in the neoplastic progression of TSAs and also suggests that a fusion between the serrated pathway of carcinogenesis and the chromosomal instability pathway may occur in some TSAs. Further studies are needed to determine the natural history and risk of malignancy of TSAs, specifically related to the anatomic site of development. PMID- 20305538 TI - Immunohistochemistry for SDHB divides gastrointestinal stromal tumors (GISTs) into 2 distinct types. AB - The Carney triad (CT) is gastrointestinal stromal tumor (GIST), paraganglioma, and pulmonary chondroma. The GISTs of CT show different clinical, molecular, and morphologic features to usual adult GISTs but are similar to the majority of pediatric GISTs. We postulated that these GISTs would show negative staining for succinate dehydrogenase B (SDHB). We performed SDHB immunohistochemistry on GISTs arising in 5 individuals with CT, 1 child, 7 individuals with GIST in young adulthood including 2 with germline KIT mutations, 3 individuals with neurofibromatosis 1, one 63-year-old female with multifocal gastric epithelioid GIST with lymph node metastases, and 104 consecutive unselected individuals with apparently sporadic GIST. The GISTs and paragangliomas arising in CT, the pediatric GIST, and the multifocal gastric GIST from the 63-year-old showed negative SDHB staining. GISTs from the 7 young adults and 3 with neurofibromatosis were SDHB positive. Of the unselected GISTs, 101 (97%) were positive. One of the negative GISTs arose in a 48-year-old female with previous recurrent multifocal gastric GISTs and the other 2 arose in females also in their 40s with gastric GISTs with epithelioid morphology. We conclude that negative staining for SDHB is characteristic of the GISTs of CT and the subgroup of pediatric GISTs which it resembles. Furthermore, when negative staining occurs in apparently sporadic GISTs in adults, the GISTs show morphologic and clinical features similar to pediatric and CT type GISTs. GISTs may therefore be divided into type 1 (SDHB positive) and type 2 (SDHB negative) subtypes. PMID- 20305539 TI - A diagnostic challenge: mild hemophilia B with normal activated partial thromboplastin time. AB - Hemophilia B is a hereditary bleeding disorder from the deficiency of factor IX (FIX) activity. Hemophilia B is caused by a mutation in the F9 gene on Xq27.1 encoding FIX and, thus, has an X-linked inheritance. The diagnosis of hemophilia B is typically suspected by significantly prolonged activated partial thromboplastin time (aPTT) on screening tests, but aPTT may be normal or minimally prolonged in mild hemophilia B. We herein describe the cases of two Korean brothers with mild hemophilia B. The proband was a 26-year-old male patient with a mild bleeding history. He had a younger brother and a male cousin of maternal side with a similar bleeding tendency. Coagulation screening tests revealed no remarkable findings, including normal aPTT at 40.0 s (STA-PTT Automate, local reference range, 29.1-41.9 s). However, factor assays revealed a significantly decreased FIX activity at 27% (67-154%). The younger brother also had mildly prolonged aPTT at 45.1 s, which was corrected on mixing test. His FIX activity was 34%. Molecular genetic analysis of F9 revealed that the brothers were both hemizygous for a missense mutation, c.280G>A (p.Gly94Arg or Gly48Arg by conventional numbering based on the mature protein). Gly94Arg (Gly48Arg) is a mutation previously described in mild hemophilia B. This report shows that aPTT can be normal even with a reagent reported to be sensitive in detecting mild hemophilia B. It is important to pay attention to the clinical and family history and perform factor assays, and molecular genetic analysis can confirm the diagnosis and reveal genotype-phenotype correlations. PMID- 20305540 TI - Migrating venous thrombosis in acute leukemia. AB - We present a 55-year-old man with acute migrating thrombophlebitis and deep vein thrombosis of muscle veins in both calves indicating occurrence of acute myelomonocytic leukemia. Thrombosis of superficial and deep veins of the lower limbs arose in spite of the adequate anticoagulation therapy with warfarin. PMID- 20305541 TI - Fibrinolytic parameters in children with noncatheter thrombosis: a pilot study. AB - Although the incidence of pediatric thrombosis has increased over the last decade, noncatheter-related deep venous thrombosis (nCDVT) is rare in children. Congenital and acquired hypercoagulable states may play an important role in the pathogenesis of nCDVT. In this study, we evaluated fibrinolytic parameters by measuring individual concentrations of fibrinolytic proteins and by tissue factor initiated whole blood thromboelastography (TEG), in which a fibrin clot was lyzed by exogenously added tissue plasminogen activator (tPA). Children with nCDVT were compared with age and sex-matched controls. TAFI concentrations were significantly higher in the patient group but there was no difference in the PAI 1, tPA and lipoprotein (a) concentrations. Significantly decreased fibrinolysis was found on TEG in the patient group suggesting that hypofibrinolysis may play an important role in the pathogenesis of nCDVT in children. To our knowledge, this is the first pediatric study that has systematically evaluated the role of fibrinolysis in the pathogenesis of DVT. Given our results, the role of fibrinolysis in the pathogenesis of nCDVT in children should be further evaluated in larger studies. PMID- 20305542 TI - Analysis of factor VIIa binding to relipidated tissue factor by surface plasmon resonance. AB - Kinetic analysis of the tissue factor (TF)-factor VIIa (FVIIa) binding interaction is helpful in investigating the structure-function relationships of TF-FVIIa. However, a wide variation exists among the reported binding affinities of FVIIa to TF, particularly when comparing KD values obtained from functional activity assays versus ligand binding studies. Surface plasmon resonance (SPR) technique was used frequently to investigate binding kinetics of FVIIa to TF in a lipid-free environment. In the present study we used TF embedded in a phospholipid bilayer for determining binding kinectis using SPR. The data revealed that FVIIa had a much higher binding affinity (>100-fold) for TF embedded in the phospholiid bilayer than TF in a lipid-free environment, approaching the KD values that were noted in the enzymatic activity assays. The present data suggest that SPR binding studies using TF embedded in phospholipids is more appropriate for investigating how FVIIa (or FVIIa mutants/derivatives) may interact with TF in physiological settings. PMID- 20305543 TI - Neonatal and childhood right atrial thrombosis: recognition and a risk-stratified treatment approach. AB - Pediatric literature and guidelines of treatment options for right atrial thrombosis (RAT) are lacking; thus, this review summarizes the available literature on RAT in infants and children. Medline search identified 35 publications, with 27 prospective or retrospective case series included for data analysis. A total of 122 cases of RAT were identified. The mean age of patients is 3.58 years (n = 86) with a strong predominance in the neonatal and infancy period. Ninety-one percent of cases were found to be associated with central venous catheters, 40.8% are premature neonates, 27.2% are postcardiac surgery patients, and 19.2% have underlying malignancies. Gut failure with total parenteral nutrition given via the central venous catheters occurred in 45.6% of patients. The most frequent presenting symptoms are respiratory distress and arrhythmia, and 56.8% (42 of 74) were asymptomatic. Our study defined high-risk features on echocardiogram as large size, more than 2 cm in any dimension, pedunculated, mobile, or snake-shaped, and mobile. Our result confirmed there is significant difference in the mortality for the high-risk group (16.7%; three of 18) versus the low risk group (0%; n = 32; P = 0.0416). Moreover, none of the asymptomatic patients showed progression in disease or died. Asymptomatic and hemodynamically stable patients with RAT who are at low risk are associated with good prognosis irrespective of treatment. We recommended removal of central venous line if possible, with or without anticoagulation for this group of patients. Systemic anticoagulation therapy should be given to all high-risk or symptomatic RAT patients. Surgical thrombectomy or thrombolytic therapy carries significant risk and should be considered individually. PMID- 20305544 TI - Hemodialysis catheter: induced giant right atrial thrombus. AB - Transient central venous hemodialysis catheters are used commonly while waiting for arteriovenous fistulas to mature. Thrombosis is a possible complication of indwelling central venous catheters utilized for hemodialysis. However, a giant right atrial thrombus is relatively rare. In this report, we present a case of right atrial thrombus related to transient indwelling hemodialysis catheter, which had been in situ for 45 days. PMID- 20305545 TI - Left ventricular geometry, ambulatory blood pressure and extra-cardiac organ damage in untreated essential hypertension. AB - BACKGROUND AND AIM: Limited information is available on the association between left ventricular (LV) geometric patterns defined according to updated criteria and blood pressure (BP) levels and extra-cardiac organ damage (OD) in human hypertension. Thus, in untreated essential hypertensives we assessed the relationship between LV geometry, ambulatory BP and markers of vascular and renal OD. METHODS: A total of 669 hypertensives were categorized in four groups according to LV geometric patterns defined by two sets of sex-specific criteria (i.e. LV mass indexed to body surface area and height) and by the relative wall thickness (RWT) partition value of 0.42. Ambulatory BP variables were derived from two 24-h monitoring sessions performed within 4 weeks. RESULTS: Lower clinic and ambulatory BP values were associated with normal LV geometry, intermediate values with either LV concentric remodelling or eccentric LV hypertrophy (LVH) and higher values with concentric LVH, regardless of the criteria used to categorize these cardiac phenotypes. A decrease in nocturnal BP dip occurred from normal LV geometry to concentric LVH and this was associated with a parallel increase in the prevalence of carotid and renal OD, which was highest in concentric LVH. In a multivariate analysis age (beta=0.204, P<0.0001), followed by LDL cholesterol (beta=0.113, P=0.004), and night-time BP (beta=0.101, P=0.009) turned out to be the best independent correlates of RWT. CONCLUSION: These findings indicate that LV geometric patterns, regardless of categorization criteria, reflect different degrees of BP load and subclinical extra-cardiac alterations and may be regarded, in addition to absolute values of LV mass, as a reliable marker of cardiovascular (CV) risk. PMID- 20305546 TI - Noonan-like/multiple giant cell lesion syndrome in two adult patients with SOS1 gene mutations. PMID- 20305547 TI - Mosaic and complete tetraploidy in live-born infants: two new patients and review of the literature. AB - Tetraploidy is a very rare finding in live-born infants. Nine infants with tetraploidy have been reported earlier. The phenotype is of variable severity and consists of prenatal and/or postnatal growth retardation, developmental delay, mental retardation, dysmorphic features, and skeletal and internal abnormalities. Here we present a girl aged 2 years and 7 months with a mosaic tetraploidy detected in lymphocytes, and a newborn boy with a complete tetraploidy, who died 30 h after birth. They both show growth retardation, microcephaly, developmental delay, and craniofacial dysmorphisms. The clinical features of 22 patients reported earlier are reviewed. PMID- 20305548 TI - Plasma hyaluronan and collateral development in patients with coronary artery disease. AB - OBJECTIVE: In-vivo studies have shown that hyaluronan (HA) can promote angiogenesis and arteriogenesis, which results in accelerated collateral development. This study is aimed at investigating the association between plasma HA levels and the extent of coronary collaterals, in patients with coronary artery disease. METHODS: A total of 253 consecutive patients, who underwent coronary angiography, were divided into three groups according to coronary angiograms: normal group, 81 patients with normal coronary angiographic findings; poor collateral group, 98 patients with at least one coronary stenosis of at least 75%, but without visible collateral circulation; good collateral group, 74 patients with at least one coronary stenosis of at least 75% with well-developed collateral circulation. Plasma HA levels were measured by radioimmunoassay. The correlation between HA levels and the extent of coronary collaterals according to the Cohen-Rentrop classification was calculated by cumulative logits models. RESULTS: Plasma HA levels were 43.71+/-2.91, 61.77+/-4.10, and 131.97+/-11.76 ng/ml, for patients in the normal, poor collateral, and good collateral groups, respectively. The good collateral group had significantly higher plasma HA levels than the poor collateral (P<0.001) and normal group (P<0.001), whereas there was no significant difference between the normal and poor collateral group. HA levels elevated with increasing Rentrop score, and the cumulative logits model showed a strong graded association between plasma HA levels and the collateral Cohen Rentrop score (odds ratio=1.021, chi2=17.811, 95% confidence interval: 1.011 1.031, P=0.000). CONCLUSION: This study suggests that elevated plasma HA levels are associated with a significant enhancement in coronary collateralization. HA may serve as a novel potential biomarker for collateral formation in patients with coronary artery disease. PMID- 20305549 TI - Impact of angiographic and intravascular ultrasound features on clinical outcome after sirolimus-eluting stent implantation for de-novo lesions in nondiabetic and type 2 diabetic patients. AB - OBJECTIVES: This study aimed to evaluate the impact of angiographic and intravascular ultrasound (IVUS) features on clinical outcome in nondiabetic and type 2 diabetic patients after percutaneous coronary intervention (PCI) with sirolimus-eluting stent (SES) implantation. METHODS: Repeat coronary angiography with IVUS imaging was performed after SES-based PCI for de-novo lesions in 128 diabetic and 327 nondiabetic patients (189 lesions and 504 lesions, respectively). The rate of major adverse cardiac events including cardiac death, non fatal myocardial infarction (MI), and target lesion revascularization during clinical follow-up was recorded. RESULTS: In-stent and in-segment late loss, intimal hyperplasia volume, and percentage volumetric obstruction were similar, but stented external elastic membrane cross-sectional area and reference/stented segment ratio were lower in diabetic than in nondiabetic patients. Incomplete stent apposition (ISA) was less frequent, but occurrence of new coronary lesions was higher in diabetic than in nondiabetic patients. Despite similar target lesion revascularization, cumulative survival rates freedom from composite cardiac death and nonfatal MI or major adverse cardiac events were reduced in diabetic patients. Cox proportional hazards model identified diabetes, left ventricular ejection fraction, minimal stent CSA, maximal ISA area, atherosclerotic progression and lesion length as independent predictors of non fatal MI or mortality at follow-up. CONCLUSION: In diabetic patients, PCI with SES implantation neutralizes the excess risk of intimal hyperplasia and decreases occurrence of ISA, but could not modify the propensity of increased adverse clinical outcomes at follow-up. PMID- 20305550 TI - Risk factors and comorbidities in a community-wide sample of patients hospitalized with acute systolic or diastolic heart failure: the Worcester Heart Failure Study. AB - OBJECTIVES: Few epidemiological studies have examined differences in the prevalence of risk factors and comorbidities in patients with systolic heart failure (HF), as compared with those with diastolic HF. METHODS: We analyzed data from 1426 residents of the Worcester (MA) metropolitan area hospitalized at all 11 greater Worcester medical centers for acute HF during 1995 and 2000 who had data available on ejection fraction (EF) findings during hospitalization. The analysis was conducted based on the presence of either normal (diastolic HF) as compared with reduced (systolic HF) EF, using an EF cutpoint of at least 50%. RESULTS: The average age of study patients was 71 years, 56% were women, and 43% had diastolic HF. Patients with diastolic HF were more likely to be older, female, obese, and to have higher systolic blood pressures and lower heart rates at the time of hospital presentation than patients with systolic HF. In contrast, patients with systolic HF had a greater prevalence of diabetes, previous myocardial infarction, and a history of alcohol abuse as compared with patients with diastolic HF. In multivariate analyses, the strongest metabolic correlates of diastolic HF were obesity, hypertension, and clustered metabolic risk factors; diabetes was associated with the occurrence of systolic HF. CONCLUSION: The results of our population-based investigation show that multiple risk factors and comorbidities are present in patients with systolic and diastolic HF. Consideration of these comorbidities and risk factors should be taken into account in distinguishing patients with diastolic HF from those with systolic HF and in their optimal management. PMID- 20305551 TI - Prognostic value of myeloperoxidase in coronary artery disease: comparison of unstable and stable angina patients. AB - BACKGROUND: Atherosclerosis is a chronic inflammatory process, and myeloperoxidase (MPO) seems to contribute directly to the pathogenesis of acute coronary syndrome (ACS). OBJECTIVE: To compare MPO levels among the patients with stable and unstable ischemic heart disease and to evaluate their independent prognostic value for cardiovascular events. METHODS: MPO and C-reactive protein (CRP) were assessed in two cohorts of coronary artery disease patients, including 178 patients with stable angina and 130 patients with ACS evaluated at the emergency department. RESULTS: MPO and CRP levels were significantly higher among patients with ACS [MPO 93 (54-127) vs. 9.9 pmol/l (5-21) and high sensitivity-CRP 11 (3-27) vs. 2.6 mg/l (1-5)]. Among patients with stable angina, high sensitivity-CRP levels greater than 3 mg/l were associated with a three-fold risk of further cardiovascular events during a mean follow-up period of 13+/-4 months, although there was no significant association between MPO levels and outcomes. Among patients with ACS, baseline MPO level was an independent predictor of major adverse cardiac events during hospitalization, odds ratio of 3.8 (95% confidence interval: 1.2-12) for the combined endpoint (death, recurrent angina, heart failure, and arrhythmia). CRP levels were associated with hospital mortality in patients with ACS, but were not independently related to cardiovascular events. CONCLUSION: Elevated MPO levels among the ACS patients suggest that this marker may participate in plaque vulnerability and instability process, whereas higher CRP levels were predictive of cardiac events only among the stable angina patients. These findings suggest distinct role of the inflammatory markers studied in the pathophysiology of coronary artery disease. PMID- 20305552 TI - Infectious intracranial complications in the neuro-ICU patient population. AB - PURPOSE OF REVIEW: To provide an overview of infectious intracranial complications secondary to invasive procedures or trauma in the neuro-ICU patient population. Nosocomial infections of the central nervous system are a serious complication contributing to morbidity, prolonged length of stay in the ICU and/or hospital, and mortality of neurocritical care patients. RECENT FINDINGS: Any type of neurosurgical interventions, specifically ventriculostomy/external ventricular drainage, constitutes a major risk factor for infectious intracranial complications. Other predisposing factors are comorbidities with immunocompromised state and the presence of a distant focus of infection. The emergence of multiresistant pathogens adds to the complexity of the management of infectious intracranial complications. In recent years, several antimicrobial agents suitable for the treatment of nosocomial central nervous system infections have been extensively studied with respect to pharmacodynamics and pharmacokinetics in serum and - of special importance in the neurocritical care setting - cerebrospinal fluid. SUMMARY: Despite recent advances in prevention and treatment, the management of nosocomial intracranial infections still poses a challenge to the neuro-ICU specialist and must consider timely diagnosis and prompt initiation of appropriate antibiotic therapy. This review focuses on the definition, epidemiology, clinical features, and therapeutical approach to this distinct complication of neurocritical care. PMID- 20305553 TI - Approaches to improving cardiac arrest resuscitation performance. AB - PURPOSE OF REVIEW: The survival rate from cardiac arrest remains poor despite advances in cardiopulmonary resuscitation (CPR) and postresuscitation therapies. Recent studies have documented many shortcomings during the performance of resuscitation care. We will review the various methods to improve the delivery of resuscitation care described in the current literature. RECENT FINDINGS: Despite the fact that quality of CPR has been shown to correlate with improved patient outcomes, conventional training methods are often insufficient in enabling healthcare providers to deliver high-quality resuscitation care. Use of simulation methods during resuscitation training can increase subsequent resuscitation quality. Additionally, automated feedback during resuscitation has been shown to improve CPR performance. Focused debriefing after resuscitation can improve CPR quality and increase initial resuscitation success. Finally, minimizing pauses in chest compressions by adopting cardiocerebral resuscitation (CCR) protocols can lead to better patient survival. Implementing these measures on a more widespread basis can improve resuscitation care and ultimately decrease patient mortality. SUMMARY: By adopting techniques such as simulation, automated feedback, training refreshers, debriefing and CCR, the quality of resuscitation performance can be increased. Future work needs to demonstrate that improved resuscitation performance correlates with decreased mortality. PMID- 20305554 TI - Using oxygen delivery targets to optimize resuscitation in critically ill patients. AB - PURPOSE OF REVIEW: The use of fluid and inotropic therapies to optimize global haemodynamic variables, in particular oxygen delivery, in critically ill patients has been a controversial area of research for more than 25 years. The aim of this review is to describe the current evidence base for this treatment and how concepts of haemodynamic optimization have evolved in recent years. RECENT FINDINGS: The inconsistent findings of a large number of small phase II trials continue to stimulate the debate about the value of this treatment approach. However, important recent developments include the use of optimization only during periods of resuscitation, more cautious doses of fluid and/or inotropic therapy, confirmation that pulmonary artery catheter use does not result in excess mortality and an improved understanding of the mechanistic effects of haemodynamic optimization. SUMMARY: These advances in our understanding have now informed the design of large randomized trials in various patient groups. The true value of haemodynamic optimization is likely to be confirmed or refuted within the next 5 years. PMID- 20305555 TI - Realistic expectations for public access defibrillation programs. AB - PURPOSE OF REVIEW: Public access defibrillation programs have increased dramatically over the past 15 years. This review will focus on their effectiveness and operational characteristics and discuss the characteristics of successful programs, which can improve outcomes. RECENT FINDINGS: Automated external defibrillators increase survival from cardiac arrest when used by a bystander. Recent studies show that the best outcomes are achieved when devices are placed in areas with a high frequency of cardiac arrest and there is ongoing supervision with emergency plans and cardiopulmonary resuscitation training. Programs are cost-effective under these circumstances, but become very inefficient when placed in areas of low risk. There are few adverse events related to the public access defibrillation programs and volunteers are not harmed. Unguided placement results in devices not being used and a decline in organizational structure of the program. As most cardiac arrests occur in the home, the impact on overall survival remains low. SUMMARY: Automated external defibrillators are highly effective at reducing death from ventricular fibrillation and easy access in public areas is most effective. Placement must be prioritized based on public health impact and characteristics of the community. PMID- 20305556 TI - Detecting critical illness outside the ICU: the role of track and trigger systems. AB - PURPOSE OF REVIEW: Critical illness is often preceded by physiological deterioration. Track and trigger systems are intended to facilitate the timely recognition of patients with potential or established critical illness outside critical care areas. The aim of this article is to review the evidence for the use of such systems. RECENT FINDINGS: Existing track and trigger systems have low sensitivity, low positive predictive values, and high specificity. They often fail to identify patients who need additional care and have not been shown to improve outcomes. The development of such systems must be based on robust methodological and statistical principles. At present, few track and trigger systems meet these standards. SUMMARY: Although track and trigger systems, combined with appropriate response algorithms, have the potential to improve the recognition and management of critical illness, further work is required to validate their utility. PMID- 20305557 TI - Evolving approaches to assessing and monitoring patient-ventilator interactions. AB - PURPOSE OF REVIEW: Patient-ventilator dyssynchrony (PVD) is prevalent in critically ill patients and causes increased work of breathing, which can lead to ventilatory muscle overload and fatigue as well as impairment in sleep efficiency, both important factors in determining ventilator duration. RECENT FINDINGS: New ways to analyze and communicate information, such as embedded computerized algorithms that are able to calculate a dyssynchrony index and enhanced ventilator graphical displays, may assist the clinician with recognition of PVD. Esophageal pressure monitoring allows the clinician to address trigger, flow and cycle dyssynchrony as well as quantify the incremental work of breathing imposed by PVD. An analysis using relationships in the equation of motion allows for onset and cycling off of breaths that match closer with the patient effort compared with current algorithms. Monitoring diaphragmatic electrical activity permits the accurate assessment of relationships between neural drive and ventilator flow delivery, and can assess the workload of the diaphragm. SUMMARY: Although computerized algorithms and user-friendly graphic displays show promise in minimizing the time to recognition of dyssynchrony, monitoring diaphragmatic electrical activity comes closest to representing the ideal in ventilator monitoring. Further work, however, is needed to demonstrate outcomes benefit to patients and to make this a reliable and user-friendly system for clinicians. PMID- 20305558 TI - Stem cells and reproduction. AB - PURPOSE OF REVIEW: To review the latest developments in reproductive tract stem cell biology. RECENT FINDINGS: In 2004, two studies indicated that ovaries contain stem cells which form oocytes in adults and that can be cultured in vitro into mature oocytes. A live birth after orthotopic transplantation of cryopreserved ovarian tissue in a woman whose ovaries were damaged by chemotherapy demonstrates the clinical potential of these cells. In the same year, another study provided novel evidence of endometrial regeneration by stem cells in women who received bone marrow transplants. This finding has potential for the use in treatment of uterine disorders. It also supports a new theory for the cause of endometriosis, which may have its origin in ectopic transdifferentiation of stem cells. Several recent studies have demonstrated that fetal cells enter the maternal circulation and generate microchimerism in the mother. The uterus is a dynamic organ permeable to fetal stem cells, capable of transdifferentiation and an end organ in which bone marrow stem cells may differentiate. Finally stem cell transformation can be an underlying cause of ovarian cancer. SUMMARY: Whereas we are just beginning to understand stem cells, the potential implications of stem cells to reproductive biology and medicine are apparent. PMID- 20305559 TI - Mental health of parents of twins conceived via assisted reproductive technology. AB - PURPOSE OF REVIEW: To review recent knowledge on mental health of parents of twins conceived via assisted reproductive technology (ART). RECENT FINDINGS: Mental health of mothers and fathers of twins conceived via ART is impaired when compared with that of ART singletons. SUMMARY: Existing studies are mainly cross sectional and most of them focus on maternal mental health. It is evident that twin parenthood is the main factor impairing the mental health in parents with ART twins. This aspect should be taken into account when counseling the couples and deciding the number of embryos for transfer in ART. Well conducted prospective longitudinal studies are needed on both maternal and paternal mental health with twins conceived via ART from transition to parenthood to and beyond toddler age covering later life with school-aged and adolescent twins. PMID- 20305560 TI - What can we learn from epigenetics in the year 2009? AB - PURPOSE OF REVIEW: Rheumatoid arthritis (RA) is a systemic, autoimmune disease resulting in the destruction of affected joints. Even though current therapies with biologics such as tumor necrosis factor-alpha blockers yield significant improvement for the patients, the disease is not curable yet. Therefore, we need novel strategies for better therapies. RECENT FINDINGS: The growing knowledge of epigenetics might give us new insights into the pathogenesis of autoimmune diseases. In the last year, several new findings about epigenetic modifications of gene expression were reported in different arthritides. These modifications describe changes in the expression of DNA that result from methylation, posttranslational modifications of the histone proteins, including acetylation/deacetylation, sumoylation, methylation and microRNAs. Most interestingly, these modifications seem to act in concert and are associated with the circadian metabolic rhythm of cells. SUMMARY: This review summarizes reports from the last year about epigenetic modifications of gene expression via acetylation/deacetylation, including sirtuins, sumoylation, methylation, microRNAs in all in rheumatoid arthritis and other arthritides, providing potential strategies for better therapies and encourages the development of specific epigenetic drugs. PMID- 20305561 TI - Lupus nephritis: where are we now? AB - PURPOSE OF REVIEW: To consider the challenges in the management of lupus nephritis with respect to diagnosis and optimal therapy for induction and maintenance of response. RECENT FINDINGS: Despite several large clinical trials in lupus nephritis, no second line drug is licensed for use in induction of remission in lupus nephritis. An important issue is how remission and flare are defined and the role of repeat renal biopsies. On the background of negative trials with mycophenolate mofetil and rituximab, there are recent data demonstrating superiority of mycophenolate mofetil in certain subgroups. New data suggest a role for tacrolimus in the treatment of lupus nephritis. Additionally, dogma is being challenged by data showing very low and even no oral steroids can be used in mycophenolate mofetil and rituximab-based regimes. SUMMARY: Despite the negative outcome of recent trials there is growing evidence that there are increasing opportunities in patients with lupus nephritis to offer treatments tailored to the individual needs of the patient based not only on the class and severity of their nephritis but also on their ethnicity, their desire to have children and their predictors of outcome. PMID- 20305563 TI - Controlling lipids in a high-risk population with documented coronary artery disease for secondary prevention: are we doing enough? AB - BACKGROUND: The prevalence of high-density lipoprotein cholesterol (HDL-C) in patients who have achieved low-density lipoprotein cholesterol (LDL-C) targets in the current era of universal statin therapy remains unknown. We conducted a study to determine the prevalence of low HDL-C in patients with documented coronary artery disease, and to determine the lipid-lowering treatment patterns in secondary prevention of coronary artery disease. METHODS: In this retrospective cohort analysis, data were obtained from the electronic database of a cardiology clinic. The Joint British Society 2 criteria were used defining low HDL-C as less than 1 mmol/l in males and less than 1.2 mmol/l in females. We compared the prevalence of low HDL-C across the following categories of LDL-C: less than 2, 2 2.5, and greater than 2.5 mmol/l. RESULTS: Two thousand and eighty-seven patients with a mean age of 64.34+/-11.94 years constituted the study sample. About 36.6% of patients in this study were found to have low HDL-C. Irrespective of sex, low HDL-C was prevalent across all levels of LDL-C, but interestingly this was most prevalent in patients with a LDL-C less than 2 mmol/l (43.06%). HDL-C level of 1.16+/-0.97 mmol/l in patients with LDL-C less than 2 mmol/l was significantly lower than 1.22+/-0.33 mmol/l in patients with LDL-C greater than 2 mmol/l, P value less than 0.01. There was a poor correlation between levels of HDL-C and LDL-C in the study population irrespective of sex or statin therapy. CONCLUSION: This study shows widely prevalent low HDL-C levels in high-risk patients across the spectrum of LDL-C levels despite statin therapy. There was no correlation between the LDL-C and HDL-C levels implying their independent relationship and, thus, the need to treat them independently. PMID- 20305562 TI - Angiogenesis and vasculogenesis in rheumatoid arthritis. AB - PURPOSE OF REVIEW: Angiogenesis is the formation of new capillaries from pre existing vessels, whereas vasculogenesis is de-novo capillary formation from endothelial precursor cells (EPCs). Current understanding of the role of angiogenesis and vasculogenesis in rheumatoid arthritis (RA) and possibilities of therapeutic intervention should be summarized. RECENT FINDINGS: There have been many recent studies on the role of the hypoxia and hypoxia-inducible factor (HIF) vascular endothelial growth factor (VEGF)-angiopoietin axis in angiogenesis associated with RA. The role of additional growth factors, chemokines, cytokines, matrix components and adhesion molecules has been further characterized. Macrophage migration inhibitory factor (MIF) may link inflammation, angiogenesis and atherosclerosis. Junctional adhesion molecules (JAMs) and focal adhesion kinases (FAKs) have recently been implicated in inflammatory angiogenesis. Novel information regarding the role of serum amyloid A (SAA) and sphingosine kinase has become available. Most of these angiogenic factors have recently been targeted using various techniques and arthritis models. Whereas angiogenesis is abundant in RA, there is defective EPC function and vasculogenesis leading to atherosclerosis and vascular disease in arthritis. Treatment with EPCs already under investigation in vascular diseases may also be attempted in RA. SUMMARY: Targeting angiogenesis and restoration of vasculogenesis may be beneficial for the therapy and outcome of RA. PMID- 20305564 TI - Depressive symptoms and heart rate variability in younger women after an acute coronary event. AB - OBJECTIVES: We investigated associations between depressive symptoms and reduced heart rate variability (HRV) in women aged 30-65 years after an acute coronary event. BACKGROUND: Younger women have an increased mortality after myocardial infarction compared with men of similar age. Depression was hypothesized to contribute to the poor prognosis, possibly mediated by increased susceptibility to arrhythmias. METHODS: The Stockholm Female Coronary Risk study comprised of 292 women aged 30-65 years who were consecutively admitted for myocardial infarction or unstable angina pectoris during a 3-year period. Depressive symptoms were assessed by means of a 9-item questionnaire. Women with no or only one depressive symptom were classified as low-depression individuals, those with two or more depressive symptoms as high-depression individuals. HRV data were calculated from 24-h ambulatory electrocardiographic recordings 3-6 months after the initial event. RESULTS: Reliable HRV data were obtained from 266 patients. Seventy women were low-depression individuals, and 196 women were high-depression individuals. In univariate analyses, the index of standard deviations of R-R intervals, very low-frequency power, low-frequency power and high-frequency power of HRV were lower in the high-depression individuals. After controlling for potential confounders (diabetes, hypertension, systolic blood pressure, body mass index and beta-blocker medication), a significant difference between low and high depression individuals was maintained for all indices except for high-frequency power. CONCLUSION: The presence of two or more depressive symptoms was associated with reduced HRV in a high-risk group of younger women after an acute coronary event. PMID- 20305565 TI - Influence of age, sex, body size, smoking, and beta blockade on key gas exchange exercise parameters in an adult population. AB - AIMS: Cardiopulmonary exercise testing (CPET) is a widely applied clinical procedure. There is uncertainty to what extent nutritional status, beta blockers and smoking should be taken into account in the interpretation of exercise parameters to describe abnormality. This study planned to consider the impact of these factors on CPET values and develop reference equations on the basis of a large-scale population-based survey. METHODS AND RESULTS: An incremental cycle exercise protocol was applied to 1708 volunteers. Individuals with structural heart disease, echocardiographic or lung function pathologies were excluded. Age, height, weight, smoking, and beta blockers were analysed for their influencing power in each sex. Reference values of CPET parameters were determined by regression analyses. The final study sample consisted of 1203 volunteers (626 female), aged 25-85 years. Exercise capacity, gas exchange, and ventilatory efficiency for carbon dioxide removal were significantly dependent on sex, age, height, weight, and cigarette smoking. In the dosages used, beta blockers did not significantly interfere with gas exchange. CONCLUSION: Sex, height, weight, and age significantly influence gas exchange. This study provides a comprehensive set of reference values in a large number of volunteers within a population-based survey, with reference values corrected for influencing factors. PMID- 20305566 TI - Age at onset and latency to treatment (duration of untreated illness) in patients with mood and anxiety disorders: a naturalistic study. AB - This study was designed to investigate and compare demographic and clinical features with specific emphasis on age at onset, age at first treatment and, in particular, on duration of untreated illness (DUI), in patients with different mood and anxiety disorders. Study sample included 729 outpatients with the following diagnoses: major depressive disorder (n=181), bipolar disorder type I (BD I, n=115) and II (BD II, n=186), generalized anxiety disorder (n=100), panic disorder (n=96), and obsessive-compulsive disorder (n=51). Main demographic and clinical variables of the sample were compared among the diagnostic groups using one-way analysis of variance or chi tests. The diagnostic groups showed significant differences in relation to age at onset and age at first pharmacological treatment and in relation to latency to treatment. In particular, patients with major depressive disorder showed the shortest DUI (39.08 months), whereas patient with BD II showed the longest DUI (97.2 months) in comparison with the other groups. Within the group with anxiety disorders (F=7.512, P<0.001), patients with panic disorder showed the shortest DUI (44.35 months), whereas patients with obsessive-compulsive disorder showed the longest DUI (90.57 months). The present findings suggest that patients with different mood and anxiety disorders show significant differences in terms of age at onset, age at first treatment and, consequently, DUI, which potentially reflect different reasons influencing treatment delay. PMID- 20305567 TI - Safety and efficacy of long-acting injectable risperidone in daily practice: an open-label, noninterventional, prospective study in schizophrenia and related disorders. AB - This postauthorization safety study evaluated the long-term safety, tolerability, and efficacy of risperidone long-acting injectable (RLAI) in routine clinical practice. In this 6-month, multicenter, European, naturalistic study, patients were included if, during routine clinical practice, long-term antipsychotic therapy with RLAI was deemed necessary by the treating physician. Efficacy measures included Clinical Global Impression-Severity and Global Assessment of Functioning. Safety was evaluated by recording treatment-emergent adverse events (AE). RLAI was initiated in 5134 patients (aged 14-94 years); predominantly male (58.6%) with paranoid schizophrenia (69.8%). RLAI initial doses were 25 mg every 2 weeks (37.0% patients), 37.5 mg (18.0%), and 50 mg (44.4%). Treatment was completed by 4314 patients (84.0%). RLAI was discontinued on account of loss to follow-up (n=346; 6.7%), insufficient response (n=116; 2.3%), and AEs (n=106; 2.1%). Clinical Global Impression-Severity significantly improved from baseline to endpoint (P<0.001). Patient functioning on the Global Assessment of Functioning scale also significantly improved from baseline to endpoint (45.4 + or - 16.0 vs. 62.4 + or - 17.7, respectively, P<0.001). Treatment-emergent AEs were recorded by 1018 (20%) of patients. AEs occurring in > or = 5% of patients were akathisia, extrapyramidal disorders, depression, psychotic disorder, anxiety, and weight gain. Serious AEs were reported by 384 (8%) patients. This study confirms good safety, tolerability, and efficacy with RLAI in routine clinical practice. PMID- 20305568 TI - The pharmacological properties of antidepressants. AB - Antidepressant drugs represent one of the main forms of effective treatment for the amelioration of depressive symptoms. Most available antidepressants increase extracellular levels of monoamines. However, it is now recognized that monoamine levels and availability are only part of the story, and that antidepressants whose mechanism of action is mainly based on the modulation of monoaminergic systems may not be able to satisfy the unmet needs of depression. Therefore, a number of compounds, developed for their potential antidepressant activity, are endowed with putative mechanisms of action not affecting traditional monoamine targets. This article briefly reviews, within a mechanistic perspective, the pharmacological profiles of representative antidepressants from each class, including monoamine oxidase inhibitors, tricyclics, norepinephrine reuptake inhibitors, selective serotonin reuptake inhibitors, norepinephrine and serotonin reuptake inhibitors, antidepressants interacting with dopaminergic, melatonergic, glutamatergic, or neuropeptide systems. The undesirable side effects of currently used antidepressants, which can often be a reason for lack of compliance, are also considered. PMID- 20305569 TI - The effect of hand burns on quality of life in children. AB - There is limited data regarding the long-term outcomes for children with hand burns. The objective of this study was to prospectively document recovery after burn injury using a validated health outcomes burn questionnaire for infants, children, and adolescents. A single center prospective study was conducted on consecutive children aged 0 to 4 years and 5 to 18 years comparing outcomes between children with and without hand burns. Age specific American Burn Association/Shriners Hospitals for Children Burn Outcomes Questionnaires were administered at admission, first clinic after discharge, 3, 6, 12, 18, and 24 months after injury. One hundred eighty-one consecutive patients were enrolled in the study. Demographic, injury, and survey outcome data were available for 145 patients for at least 24 months after injury. Children with hand burns had significantly longer hospitalization, intensive care unit days, ventilator days, and TBSA burns. Initial Burn Outcomes Questionnaire scores for children with hand burns were significantly lower than controls and children with burns not involving the hand. For ages 0 to 4 years and 5 to 18 years, only the domain specific to upper extremity function was significantly decreased between the groups over the entire study period. Despite severe injury, children with hand burns have continued improvement in quality of life for at least 2 years after injury. The presence of a hand burn in the context of large TBSA burn is a marker of more severe acute illness and predicts increased resource utilization. Rehabilitative efforts after upper extremity injury should continue to target both physical function and the psychosocial impact of burn injury. PMID- 20305570 TI - What does posttraumatic growth mean to Chinese burn patients: a phenomenological study. AB - The purpose of this research was to explore dimensions of posttraumatic growth (PTG) in the population of mainland China and to find out the factors facilitating positive change. Ten patients with severe burn injuries were recruited from a metropolitan hospital in Shanghai. Sampling was purposive; qualitative phenomenological methodology was used to depict the main theme, the data were collected through individual semi-structured interviews using open ended questions. A reflective diary was also kept. The findings are presented under two thematic headings: "process of PTG" and "presentation of PTG." Results indicate that there are commonalities between the Chinese sample and Tedeschi and Calhoun's (Psychol Inq 2004;15:1-18) model of the process and outcomes of PTG. There are some differences; specifically, "for the significant others" is an important facet in the process of PTG; also there is no clear growth of a spiritual or a religious aspect. PMID- 20305571 TI - Survey on current hydrotherapy use among North American burn centers. AB - The authors have reviewed hydrotherapy practices in North American burn centers and described the epidemiology of hydrotherapy-associated nosocomial infections. A web-based survey was distributed to the directors of all burn care facilities listed by the American Burn Association. Questions addressed aspects of practice, including the method, additives, disposable liners, decontamination practices, nosocomial pathogens, and perceptions regarding the "ideal" method of hydrotherapy. The response rate was 44%, 59 of 142 centers, or 827 of 1900 beds. Hydrotherapy is regularly used by 83% of centers. Among these centers, 10% use exclusively immersion hydrotherapy (IH), 54% use exclusively shower cart hydrotherapy (SCH), and 35% use a combination of IH and SCH. Disposable liners are used at 80% of centers. Tap water alone is used by 51% of centers, 27% add detergent, 16% chlorhexidine, and 7% povidone-iodine. The majority of centers (57%) do not routinely culture their hydrotherapy equipment, 20% culture weekly, 7% monthly, and 17% less than once per month. Directors believe that Pseudomonas aeruginosa, methicillin-sensitive Staphylococcus aureus, and methicillin resistant S. aureus are the most common nosocomial pathogens, followed by Acinetobacter species and Candida albicans. The relative frequency of occurrence of the first three pathogens did not vary with regard to the hydrotherapy method used. Given the opportunity to redesign, 45% of burn unit directors would implement SCH only, 42% a combination of SCH and IH, 2% exclusively IH, and 11% no hydrotherapy or bedside irrigation only. The prevalence of hydrotherapy use at North American burn centers has decreased since 1990 (83% vs 95%), yet continues to be used at the majority of centers. The use of IH has also declined (55% vs 81%). The trend away from the exclusive use of IH will likely continue, because more centers incorporate showering methods. PMID- 20305573 TI - Acetaminophen dose does not predict outcome in acetaminophen-induced acute liver failure. AB - BACKGROUND: Acetaminophen is a dose-dependent toxin. Prognosis in severe acute liver injury is related presumably in part to the dose ingested. We sought to assess the value of acetaminophen dosing information in patients with acute liver failure (ALF) due to acetaminophen toxicity to determine the role of dose as a prognostic indicator. METHODS: Prospective data from 113 patients with ALF having single-time-point ingestions of acetaminophen were analyzed. Multivariate and chi tests were used to determine the relationship of dose to clinical outcome. We also used the Mann-Whitney U test to compare prognosis and survival in ALF with acetaminophen dose ingested. RESULTS: Multivariate and chi analyses failed to show any relationship between acetaminophen dose and spontaneous survival. A separate analysis showed no correlation between acetaminophen dose and clinical prognostic indicators. CONCLUSIONS: Dose of acetaminophen ingested did not seem to play a role in prognosis. The most important prognostic factor was coma grade on admission to study. Acetaminophen dosing information is not always obtainable. When it is, it adds little to the clinical assessment. Severity of encephalopathy is a more reliable indicator of prognosis in these critically ill patients. PMID- 20305572 TI - Instability in teacher ratings of children's inattentive symptoms: implications for the assessment of ADHD. AB - OBJECTIVE: To examine the cross-grade stability of clinically elevated teacher ratings of inattentive symptoms in 3 samples of elementary schoolchildren. PARTICIPANTS AND METHODS: Samples 1 and 2 included 27 first graders and 24 fourth graders, respectively, identified based on clinically elevated teacher ratings of inattentive symptoms. The third sample included 28 children in grades 1 to 4 from the Multimodal Treatment Study of attention-deficit hyperactivity disorder (Multimodal Treatment Study of Children with attention-deficit hyperactivity disorder Study) with a confirmed attention-deficit hyperactivity disorder diagnosis. Teacher ratings of inattentive symptoms were completed an average of 12 to 14 months apart so that cross-grade stability of elevated ratings could be computed for each sample. RESULTS: In all 3 samples, clinically elevated ratings persisted for less than 50% of children and between 25% and 50% had ratings that declined to within the normative range. The decline in attention difficulties was not related to hyperactivity, oppositional behavior, or anxiety at baseline, nor was it explained by children beginning medication treatment. CONCLUSIONS: Many elementary-aged children rated by their teachers as highly inattentive are not considered to demonstrate these problems the following year, even children with a confirmed attention-deficit hyperactivity disorder diagnosis. The instability in clinically elevated teacher ratings found across 3 independent samples highlights the importance of annual reevaluations to avoid treating children for problems that may no longer be present. PMID- 20305574 TI - Cigarette smoke alters tissue inhibitor of metalloproteinase 1 and matrix metalloproteinase 9 levels in the basolateral secretions of human asthmatic bronchial epithelium in vitro. AB - BACKGROUND: Asthma, a major cause of chronic lung disease worldwide, has increased in prevalence in all age and ethnic groups, particularly in urban areas where cigarette smoking is common. Cigarette smoke (CS) significantly impacts the development of asthma and is strongly associated with increased asthma-related morbidity. PURPOSE: To evaluate bioinformatic analyses predicting that CS would alter expression of tissue inhibitor of metalloproteinase (TIMP) 1 and matrix metalloproteinase (MMP) 9 in asthmatic epithelium. METHODS: Primary differentiated normal (n = 4) and asthmatic (n = 4) human respiratory epithelia on collagen-coated Transwells at air-liquid interface were exposed for 1 hour to CS condensate (CSC) or hydrogen peroxide (H2O2). Tissue inhibitor of metalloproteinase 1 and MMP-9 protein levels were measured at 24 hours by enzyme linked immunosorbent assay in cell lysates and in apical and basolateral secretions. RESULTS: Tissue inhibitor of metalloproteinase 1 and MMP-9 levels in the apical secretions of normal and asthmatic epithelia were unchanged after exposure to CSC and H2O2. However, CSC increased TIMP-1 levels in the basolateral secretions of both normal and asthmatic epithelia, but decreased MMP-9 levels only in asthmatic basolateral secretions, resulting in a 2.5-fold lower MMP 9/TIMP-1 ratio that corresponded to decreased MMP-9 activity in CS-exposed asthmatic basolateral secretions. CONCLUSIONS: These data validate our prior bioinformatic analyses predicting that TIMP-1 plays a role in the stress response to CS and indicate that asthmatics exposed to CS may be more susceptible to MMP-9 mediated airway remodeling. This is in agreement with the current paradigm that a reduction in the MMP-9/TIMP-1 ratio is a milieu that favors subepithelial airway remodeling in chronic asthma. PMID- 20305575 TI - A novel missense mutation in cathepsin K (CTSK) gene in a consanguineous Pakistani family with pycnodysostosis. AB - BACKGROUND: Deficiency of cathepsin K (CTSK), a lysosomal cysteine protease, has been shown earlier as a cause of an autosomal recessive osteosclerotic skeletal dysplasia pycnodysostosis. The objective of the present study was to identify the potential sequence variants in CTSK gene in a large consanguineous Pakistani family with pycnodysostosis. METHODS: Genotyping of 4 affected and 6 unaffected members of the family was performed using polymorphic microsatellite markers linked to CTSK gene on chromosome 1q21. To screen for pathogenic mutation, exons and splice junctions of CTSK gene were polymerase chain reaction amplified from genomic DNA and sequenced directly in an automated DNA sequencer. RESULTS: Microsatellite analysis showed linkage of the family to CTSK gene on chromosome 1q21. Sequence analysis revealed a novel missense mutation c.728G>A (p.G243E) in exon 6 of the CTSK gene. CONCLUSIONS: A novel missense mutation was identified in CTSK gene in a Pakistani family with 5 individuals affected with autosomal recessive pycnodysostosis. PMID- 20305576 TI - Exchanging carbohydrate or protein for fat improves lipid-related cardiovascular risk profile in overweight men and women when consumed ad libitum. AB - BACKGROUND: The impact of low-fat diets on the plasma lipoprotein profile is incompletely understood. METHODS: We conducted two 16-week dietary studies to compare the effects of a moderate-fat (mod-FAT) baseline diet with isocaloric and ad libitum low-fat diets rich in either carbohydrates (high-CHO, n = 16) or protein (high-PRO, n = 19) on plasma lipids, post-heparin lipase activities, cholesteryl ester transfer protein, and phospholipid transfer protein. RESULTS: Switching from the mod-FAT to the isocaloric high-CHO diet lowered plasma high density lipoprotein cholesterol concentrations (P < 0.001) and tended to increase triglyceride levels (P = 0.087). Cholesterol content in the larger, buoyant low density lipoprotein (LDL) fractions decreased, whereas those of the very-low density lipoprotein, intermediate-density lipoprotein, and smaller, denser LDL fractions tended to increase. These changes were largely reversed when subjects lost weight by consuming this high-CHO diet ad libitum. Switching from the mod FAT diet to the isocaloric high-PRO diet did not increase cholesterol content in the small-dense LDL fraction and led to decreases in both LDL and high-density lipoprotein cholesterol in plasma (P < 0.001 for both).Consumption of the high protein ad libitum diet accompanied by weight loss did not change plasma lipids further, except for a shift of cholesterol from dense low-density lipoprotein fractions to more buoyant low-density lipoprotein fractions. Cholesteryl ester transfer protein concentrations decreased with high-cholesterol feeding, whereas cholesteryl ester transfer protein concentrations and hepatic lipase and phospholipid transfer protein activities all decreased during high-protein feeding. CONCLUSIONS: Both high-CHO and high-PRO diets improve plasma lipid related risk of cardiovascular disease when consumed ad libitum. PMID- 20305577 TI - Longitudinal sex differences during landing in knee abduction in young athletes. AB - PURPOSE: The objective of this study was to determine whether biomechanical and neuromuscular risk factors related to abnormal movement patterns increased in females, but not males, during the adolescent growth spurt. METHODS: A total of 315 subjects participated in two testing sessions approximately 1 yr apart. Male and female subjects were classified on the basis of their maturation status as pubertal or postpubertal. Three trials of a drop vertical jump (DVJ) were collected. Maximum knee abduction angle and external moments were calculated during the DVJ deceleration phase using a three-dimensional motion analysis system. Changes in knee abduction from the first to second year were compared among four subject groups (female pubertal, female postpubertal, male pubertal, and male postpubertal). RESULTS: There were no sex differences in peak knee abduction angle or moment during DVJ between pubertal males and females (P > 0.05). However, pubertal females increased peak abduction angle from first to second year (P < 0.001), whereas males demonstrated no similar change (P = 0.90) in the matched developmental stages. After puberty, the peak abduction angle and moment were greater in females relative to males (angle: female -9.3 degrees +/- 5.7 degrees , male -3.6 degrees +/- 4.6 degrees , P < 0.001; moment: female 21.9 +/- 13.5 N.m, male -13.0 +/- 12.0 N.m, P = 0.017). CONCLUSIONS: This study identified, through longitudinal analyses, that knee abduction angle was significantly increased in pubertal females during rapid adolescent growth, whereas males showed no similar change. In addition, knee abduction motion and moments were significantly greater for the subsequent year in young female athletes, after rapid adolescent growth, compared with males. The combination of longitudinal, sex, and maturational group differences indicates that early puberty seems to be a critical phase related to the divergence of increased anterior cruciate ligament injury risk factors. PMID- 20305578 TI - Generalized equations for estimating DXA percent fat of diverse young women and men: the TIGER study. AB - PURPOSE: Popular generalized equations for estimating percent body fat (BF%) developed with cross-sectional data are biased when applied to racially/ethnically diverse populations. We developed accurate anthropometric models to estimate dual-energy x-ray absorptiometry BF% (DXA-BF%) that can be generalized to ethnically diverse young adults in both cross-sectional and longitudinal field settings. METHODS: This longitudinal study enrolled 705 women and 428 men (aged 17-35 yr) for 30 wk of exercise training (3 d.wk(-1) for 30 min.d(-1) of 65%-85% predicted VO2max). The distribution of ethnicity was as follows: 37% non-Hispanic white, 29% Hispanic, and 34% African-American. DXA-BF%, skinfold thicknesses, and body mass index (BMI) were collected at baseline and after 15 and 30 wk. RESULTS: Skinfolds, BMI, and race/ethnicity were significant predictors of DXA-BF% in linear mixed model regression analysis. For comparable anthropometric measures (e.g., BMI), DXA-BF% was lower in African-American women and men but higher in Hispanic women compared with non-Hispanic white. Addition of BMI to the skinfold model improved the SEE for women (3.6% vs 4.0%), whereas BMI did not improve prediction accuracy of men (SEE = 3.1%). CONCLUSIONS: These equations provide accurate predictions of DXA-BF% for diverse young women and men in both cross-sectional and longitudinal settings. To our knowledge, these are the first published body composition equations with generalizability to multiple time points, and the SEE estimates are among the lowest published in the literature. PMID- 20305579 TI - Pedometer-measured physical activity and health behaviors in U.S. adults. AB - U.S. adults may have lower levels of ambulatory physical activity compared with adults living in other countries. PURPOSE: The purpose of this study was to provide descriptive, epidemiological data on the average number of steps per day estimated to be taken by U.S. adults and to identify predictors of pedometer measured physical activity on the basis of demographic characteristics and self reported behavioral characteristics. METHODS: The America On the Move study was conducted in 2003. Individuals (N = 2522) aged 13 yr and older consented to fill out a survey, including 1921 adults aged 18 yr and older. Valid pedometer data were collected on 1136 adults with Accusplit AE120 pedometers. Data were weighted to reflect the general U.S. population according to several variables (age, gender, race/ethnicity, education, income, level of physical activity, and number of 5- to 17-yr-old children in the household). Differences in steps per day between subgroups were analyzed using unpaired t-tests when only two subgroups were involved or one-way ANOVA if multiple subgroups were involved. RESULTS: Adults reported taking an average of 5117 steps per day. Male gender, younger age, higher education level, single marital status, and lower body mass index were all positively associated with steps per day. Steps per day were positively related to other self-reported measures of physical activity and negatively related to self-reported measures on physical inactivity. Living environment (urban, suburban, or rural) and eating habits were not associated with steps per day. CONCLUSIONS: In the current study, men and women living in the United States took fewer steps per day than those living in Switzerland, Australia, and Japan. We conclude that low levels of ambulatory physical activity are contributing to the high prevalence of adult obesity in the United States. PMID- 20305580 TI - Placental testing for Toxoplasma gondii is not useful to diagnose congenital toxoplasmosis. AB - We examined 785 placentas, including 51 from documented cases of congenital toxoplasmosis. Toxoplasma was detected in 16 placentas, including 1 in which congenital toxoplasmosis was ruled out. Placental screening had poor sensitivity (25%) but good specificity (99%), positive predictive value (93%), and negative predictive value (95%). PMID- 20305581 TI - Role of rhinovirus C respiratory infections in sick and healthy children in Spain. AB - BACKGROUND: Recently a new genogroup of human rhinovirus (HRV) has been described and named HRV-C. The relative importance of HRV-C in viral respiratory tract illnesses is unknown. OBJECTIVE: We looked for HRV-C in pediatric patients with respiratory tract infections to determine the incidence of HRV-C and its role in sick and healthy children. We describe the clinical differences associated with HRV-C infections and other HRV genogroups. PATIENTS AND METHODS: From January 2004 to December 2008, a prospective study was conducted in children younger than 14 years who were admitted with respiratory infection to the Pediatrics Department of the Severo Ochoa Hospital in Madrid, Spain. Specimens of nasopharyngeal aspirate were taken for virologic study with polymerase chain reaction, and clinical data were recorded. HRV specimens were genotyped. We studied the frequency of HRV-C infections, the clinical course of these patients and the differences with other HRV genogroups (HRV-A and HRV-B). Presence of HRV C was also studied in a group of healthy children. RESULTS: HRV was detected in 424 of 1555 episodes of illness (27.2%) and in 26 of 211 healthy children (12.3%) (P < 0.001). We amplified at random 248 of them (227 hospitalized children and 21 healthy children): 132 (53.2%) had HRV-A, 28 (11.2%) had HRV-B, and 88 (35.4%) HRV-C. HRV-C infections were associated with asthma, recurrent wheezing, and bronchiolitis but were not significantly different from the HRV-A genogroup. Nevertheless, significant clinical differences were observed between the HRV-B genogroup and the other groups: more frequent infiltrate on chest radiograph (P = 0.017), fever (P = 0.052), diagnosis of pneumonia (P = 0.01), and antibiotic treatment (P = 0.004). CONCLUSIONS: HRV-C infections were frequent in hospitalized children with respiratory diseases and were associated with asthma, recurrent wheezing, and bronchiolitis. No clinical differences were found with the HRV-A group: HRV-B group had clinical differences with both the other groups. PMID- 20305582 TI - Nosocomial transmission of respiratory syncytial virus in neonatal intensive care and intermediate care units: a prospective epidemiologic study. AB - To test the hypothesis that a considerable number of preterm infants acquire respiratory syncytial virus (RSV) within the hospital during the postnatal stay, a prospective epidemiologic survey was performed. Nasopharyngeal swabs were taken twice weekly for a period of 8 weeks from preterm infants, medical/nursing staff, and parents during the peak of RSV season 2007/2008 and tested for RSV by polymerase chain reaction. Of 1002 samples, only 4 tested positive (2 from a patient, 2 from staff). Sequence analyses of the G protein demonstrated that nosocomial transmission did not occur between these individuals. PMID- 20305583 TI - Impact of immunosuppressants on the therapeutic efficacy of in vitro-expanded CD4+CD25+Foxp3+ regulatory T cells in allotransplantation. AB - BACKGROUND: Although the therapeutic potential of regulatory T lymphocytes (Tregs) in preventing allograft rejection has been well documented, accumulating evidence indicates that supplemental measures, such as concomitant use of immunosuppressive agents, are essential for effective application of Treg cell therapy in clinical transplantation. Thus, it is important to know the effect of immunosuppressive agents on Treg cell therapy. METHODS: We examined the impact of various immunosuppressive agents on the in vivo proliferation and therapeutic efficacy of in vitro-expanded Tregs using the murine graft-versus-host reaction and skin allograft model (BDF1 [H-2] to C57BL/6 [H-2]), respectively. RESULTS: All six immunosuppressive agents tested inhibited the alloantigen-stimulated proliferation of Tregs as efficiently as they inhibited the proliferative response of conventional CD3 T cells. We further show that blockade of the CD40 CD40L interaction by treatment with a MR-1 antibody significantly increased the therapeutic efficacy of Tregs, a synergistic effect that seemed to be related to the strong regulatory activity of adoptively transferred Tregs together with effector T-cell hyporesponsiveness. Although concomitant use of rapamycin marginally augmented the therapeutic effectiveness of Tregs, mycophenolate mofetil and cyclosporine A at their full therapeutic doses exerted an antagonistic effect on Treg cell therapy. CONCLUSION: These results demonstrate that inhibition of CD40-CD40L interaction or treatment with rapamycin could be successfully combined with in vitro-expanded Treg cell therapy, but the concomitant use of mycophenolate mofetil or cyclosporine A in this type of Treg cell therapy should be carefully considered. PMID- 20305584 TI - Myth and reality of pragmatic trials. PMID- 20305585 TI - Management of depression in the presence of pain symptoms. AB - Somatic illness is frequently associated with depression and anxiety and major depression significantly increases risk of severe medical conditions, e.g. cardiovascular illness. One of the most frequent comorbidities is that of depression and pain. Alterations in noradrenergic and serotonergic neurotransmissions in the central nervous system have been implicated in the joint pathophysiology of depression and chronic pain. Antidepressants, alone or in combination with psychotherapy, are an effective treatment option in such cases. The newer dual action antidepressants (milnacipran, venlafaxine, duloxetine) acting specifically on both noradrenergic and serotonergic neurotransmitter systems are presumably more reliable in pain management. So far, the most extensively studied drug has been duloxetine. Twelve randomized placebo controlled trials with the total number of 4,108 patients suffering from pain associated with major depressive disorder suggested consistent analgesic efficacy of duloxetine, especially in fibromyalgia and peripheral neuropathic pain. PMID- 20305586 TI - Niacin skin flush test: a research tool for studying schizophrenia. AB - BACKGROUND: A body of biochemical evidence suggests that abnormal phospholipid metabolism may play a role in the etiology of schizophrenia, and possibly, other psychiatric and neurological diseases. Niacin, a B-complex vitamin, induces prostaglandin synthesis, vasodilatation, and skin flushing when applied as a solution on the skin or taken orally. In schizophrenia, diminished or absent skin response to niacin represents a robust finding. RESULTS: Attenuated niacin skin flush response has been analysed as a potential biochemical marker of impaired prostaglandin signaling in schizophrenia. Diminished skin redness after topical application of niacin might be caused by a reduced level of the precursor arachidonic acid in the peripheral membranes, increased activity of the enzyme phospholipase A2, abnormal expression of niacin or prostaglandin receptors, or poor vasomotor activity of cutaneous capillary walls. Heritability estimates established in several studies support niacin skin flush response as a vulnerability trait for the development of psychosis. However, the exact mechanism of a reduced skin flush, the possible influence of the long-term use of antipsychotics, and the usefulness of the test for diagnostic purpose are not clear yet. CONCLUSIONS: Niacin skin flush test is a simple, non-invasive and easily replicable method in the research of schizophrenia. The studies investigating niacin flushing in schizophrenia are numerous but incoherent regarding methods of niacin application and evaluation of the results. New studies, controlling adequately for age, sex, drug abuse, diet, as well as genetic factors that may influence the intensity and reaction time, are necessary to clarify the usefulness of niacin testing in psychiatry. PMID- 20305587 TI - Case management - a pillar of community psychiatry. AB - This review is describing different models of case management, showing their similarities and differences with regards to the way they operate. Good relationship between patient and case manager, application of the biopsychosocial model, availability of psychosocial treatment methods and rehabilitation programs, and individual treatment plan are all important factors in case management's success. Large number of studies supports the application of case management in practice as effective treatment method in treating people with severe mental disorder, particularly those, who are less co-operative. Therefore, the implementation of case management into psychiatric practice should be supported. PMID- 20305588 TI - Self-poisoning suicide attempts among students in Tehran, Iran. AB - BACKGROUND: This study aim was to describe the epidemiology of intentional self poisoning among students. SUBJECTS AND METHODS: A cross-sectional study was conducted on self-poisoned students admitted to Loghman-Hakim Hospital in Tehran, Iran. Variables studied included age, sex, substance abuse, personal history, familial history and the immediate precipitant for the suicide attempt. RESULTS: A total of 248 students (200 F and 48 M) studied. The mean age was 16.3+/-1.42 years. Self poisoning with a pharmaceutical agent was the most common attempt modality (87.5%). The most common precipitant for the suicide attempt was family conflict (54.4%), followed by romantic disappointment (29.4%). The most common psychiatric disorders were adjustment disorder (84.3%). and depression (18.1%). CONCLUSION: The emphasis in student suicide prevention programs must be on early identification of students at risk, and appropriate treatment of episodes of psychopathology. PMID- 20305589 TI - A study of Hungarian adolescent outpatients suffering from self-injurious behaviour. AB - In this pilot study (Study A), the authors administered the Hungarian standard version of Beck Depression Inventory (BDI) and the translated version of the Ottawa Self Injury Inventory (OSI) to students of 3 educational facilities in a county town. Fourteen to eighteen year old pupils were tested in order to measure the key symptoms of depression and the frequency and characteristics of self injurious behaviour among this sample of the high school population. Twentysix youngsters were found to have had any form of self-injurious actions in their life-time. The paper presents descriptive data on the basis of statistics of symptom occurence. Although the depressive symptoms have an expected correlation with the self-injurious ideas,depression seems not to have the same relationships with actual self-harm action. In study B, the authors present descriptive statistics on the data of 48 female outpatients from the total pool of 72 adolescents aged 14 through to-18 years (average age 16.1 years) showing symptoms of self-injurious behavior according to the Ottawa Self Injury Inventory (OSI). All patients were recruited from a one-year clinical,representative sample of the "Pannonia" multicentre adolescent psychiatry survey. Ten point two percent of consecutively referred and 25.6% of treated adolescent patients had symptoms of self-injurious behavior over a one-year period in 4 Transdanubian Child Psychiatric Centers, which is more frequent than the expected rate. Referring to the clinical diagnoses of adolescents confirmed by M.I.N.I. Plus Diagnostic Interview, the authors estimate, that the majority of these young people suffered from episode(s) of present or past major depression, from whatever form of anxiety disorder and/or from suicidal behaviour. The study presents details of risk behavior including motivations, frequency of acts, ideas, afflicted body regions, emotional correlates, secondary obtained benefits , escalation of problem behavior and consequences in detail. PMID- 20305590 TI - Dropout, early termination and detachment from a public psychiatric clinic. AB - BACKGROUND: Dropout from an outpatient clinic is the loss of a patient to scheduled follow-up. Due to movement of mental health care to the community, adherence to ambulatory care is crucial to maintain stability among individuals with mental disorders. We hypothesized that patients drop out from ambulatory psychiatric care when regardless of the therapist's evaluation, they feel that they have recovered, or because they are dissatisfied with treatment. The aim was to examine the phenomenon of premature termination of treatment in a public community-based ambulatory psychiatric clinic serving a catchment area with a population of 200,000. SUBJECTS AND METHODS: The study sample was drawn from patients who had at least one ambulatory therapy session during the previous five years, immediately or shortly following initial treatment and who were subsequently lost to follow-up. Participants completed a questionnaire that evaluated their satisfaction with treatment and described their reasons for early termination of treatment. RESULTS: The sample included eighty-two patients. Eighty percent of the responders (N=65) terminated therapy on their own, and twenty percent (N=17) decided to end treatment together with their therapists. DISCUSSION: Increased involvement of patients in treatment planning, duration and end of therapy, may improve attendance in ambulatory mental health care settings. CONCLUSIONS: Though dropouts generally reported satisfaction with the ambulatory service, some explained early termination of treatment as being due to dissatisfaction with the therapist, the type of treatment or because of therapist turnover. Others terminated treatment because they felt their problems were solved or their conditions had improved, though therapists had determined otherwise. PMID- 20305591 TI - Schizophrenia spectrum psychosis in a Croatian genetic isolate: genealogical reconstructions. AB - BACKGROUND: Schizophrenia spectrum psychosis is a chronic mental disorder, based on a range of genes whose expression can be altered by different environmental factors. SUBJECTS AND METHODS: In this archival and demographic study of genetic isolate we show an incidence of schizophrenia spectrum psychosis in a minority population and transmission of schizophrenia spectrum psychosis through several generations of two families in an isolated rural area of Dalmatia from the second half of 19th and the first half of 20th century. RESULTS: The incidence of schizophrenia spectrum psychosis was between 0.58 and 2.58 per 1000 inhabitants. The genogram of Family 1 shows that out of 182 descendants in six generations, there were 27 people with schizophrenia spectrum psychosis. Schizophrenia spectrum psychosis occurred in two men who were born from a relationship of a mother with her relative. The genogram of Family 2 shows that 19 out of 86 descendants in five generations suffered from schizophreniform psychosis. CONCLUSION: The high occurrence of schizophrenia spectrum psychosis in an isolated village in central Dalmatia is in accordance with the results of earlier studies in that region. The fact that psychosis occurs in varying frequency, without obvious regularity, can be explained by the irregular expression of risk genes as well as by exogenous factors which may affect the activity of the key chromosome areas. Occurrence of psychosis in people born from incestuous relationships indicates the importance of genetic factors in the development of the disorder. PMID- 20305592 TI - General practice meeting the needs for psychiatric care in Croatia. AB - BACKGROUND: In recent decades, general practitioners (GPs) have become critical components of mental health services. However, in Croatia the role of GPs in mental health services is still mostly perceived as "gate keeping", whereas seeking help for serious mental illnesses is mostly restricted to psychiatrists. The aim of this study is to investigate the practices and attitudes of family doctors in providing care for psychiatric patients. SUBJECTS AND METHODS: The study included 111 GPs, working in 38 different locations in four major towns in Croatia. Data were collected using a questionnaire, specifically designed for the purpose of this study. RESULTS: By their own estimation, GPs prescribed antidepressants without a psychiatrist's recommendation in about 37% of patients who use them. Also, GPs prescribed sedatives without a psychiatrist's recommendation in about 60% of patients who use them. Although certain categories of psychiatric patients (elderly, patients with PTSD) were almost always referred to a psychiatrist, it was GPs' attitudes toward psychiatric casualties and their proneness to prescribe antidepressants and sedatives without a psychiatrist's recommendation that predicted whether a patient will be treated by himself of referred to a psychiatrist. "Interest/Competency" and "Knowledge" of the GPs positively correlated with the number of courses attended as a part of continuous medical education (CME). CONCLUSION: Overall, the role of GPs in mental health services in Croatia is changing into a more active one, as a significant portion of patients with depression and anxiety are being treated by GPs. Personal interest and self confidence in proper knowledge and skills, in part acquired also from current CME programs, are determinants of higher autonomy of GPs in treating psychiatric patients. Psychiatrists, as active promoters of community mental health should more actively encourage their alliance with GPs, especially through offering higher quality CME courses. PMID- 20305593 TI - Hamilton anxiety scale (HAMA) in infertile women with endometriosis and its correlation with magnesium levels in peritoneal fluid. AB - BACKGROUND: Endometriosis is a complex disease that can result in substantial morbidity, including chronic pain, dysmenorrhea and dyspareunia. There are contradictory reports regarding the connection between acute and chronic stress and magnesium levels in body fluids. SUBJECTS AND METHODS: A prospective study included 87 patients undergoing laparoscopy. The study group included 40 women with endometriosis and the control group consisted of 47 women with other causes of infertility. The levels of fright were determined using HAMA scale. The measurements of Mg levels were performed using biochemical analyzer "Monarch Plus". RESULTS: One day before the operation, HAMA score was 9.54+/-7.34 in the women with endometriosis, and 6.69+/-5.51 in the women without endometriosis. The morning before the operation, HAMA score was 8.64 +/- 8.10 in the women with endometriosis, and 4.29+/-2.29 in the women without endometriosis. The second postoperative day, HAMA score was 8.96+/-7.60 in the women with endometriosis and 6.92+/-5.16 in the women without endometriosis. Higher HAMA score in the women with endometriosis, in comparison with the control group, in all three time periods has been found, but the differences were not statistically significant (p>0.05). A negative correlation between the concentration of Mg in peritoneal fluid and HAMA score was found in the control group (p<0.01). CONCLUSIONS: In infertile women without endometriosis a correlation between Mg concentration in peritoneal fluid and HAMA score was found. No such correlation was found in the women with endometriosis, possibly due to a systemic disorder in endometriosis that might affect Mg transport through the cell membrane. PMID- 20305594 TI - Metabolic syndrome in patients with psychotic disorders: diagnostic issues, comorbidity and side effects of antipsychotics. AB - BACKGROUND: Metabolic syndrome and other cardiovascular risk factors are highly prevalent in people with schizophrenia. Metabolic syndrome can contribute to significant morbidity and premature mortality and should be accounted for in the treatment of mental disorders. Along with results of numerous investigations regarding metabolic syndrome, different issues have occurred. The aim of this article is to review literature regarding diagnostic and treatment of metabolic syndrome and point at some issues regarding diagnostic and treatment of metabolic syndrome in patients with psychotic disorders and in general population. CONTENT ANALYSIS OF LITERATURE: Literature research included structured searches of Medline and other publications on the subject of metabolic syndrome, particularly diagnostic and treatment of metabolic syndrome in patients with psychotic disorders and in general population. CONCLUSION: Despite numerous investigations of metabolic syndrome, many issues remain unclear, becoming objectives for future research. The experts disagree in their opinions on particular issues, such as clustering risk factors, importance of particular diagnostic procedures for the early detection and monitoring of metabolic syndrome and the role of antipsychotics in occurrence of metabolic syndrome. There is, however, unique attitude about importance of early detection and treatment of metabolic syndrome as well as necessity of further investigations. PMID- 20305595 TI - Bipolar disorder and metabolic syndrome: comorbidity or side effects of treatment of bipolar disorder. AB - OBJECTIVE: There is evidence that people with mental disorders are more likely to suffer from metabolic syndrome. In the last decades there has been an increase in interest for researching metabolic syndrome in psychiatric patients and plenty of evidence about their association. However, investigations on the prevalence of metabolic syndrome in patients with bipolar disorder are still surprisingly rare. The aim of this paper is to analyze comorbidity of bipolar disorder and metabolic syndrome, and the association of treatment with antipsychotics and mood stabilizers with metabolic syndrome, as well as to point out the necessity of appropriate preventive measures and treatment of metabolic syndrome in patient with bipolar disorder. CONTENT ANALYSIS OF LITERATURE: Literature research included structured searches of Medline and other publications on the subject of comorbidity of bipolar disorder and metabolic syndrome, and the association of treatment with antipsychotics and mood stabilizers with metabolic syndrome, as well as preventive measures and treatment of metabolic syndrome in patient with bipolar disorder. CONCLUSION: Metabolic syndrome is present in 8-56% of patients suffering from bipolar disorder. Metabolic syndrome in patients with bipolar disorder can significantly contribute to morbidity and mortality, and it is certainly necessary to think of it, to take adequate preventive and therapeutic measures in treating its individual components. Further investigation on association between bipolar disorder and metabolic disorder, and the association of treatment with antipsychotics and mood stabilizers with metabolic syndrome are necessary. PMID- 20305596 TI - Suicidality and side effects of antidepressants and antipsychotics. AB - Antidepressants and antipsychotics can cause side effects in various organs and organic systems, and some (and) in the central nervous system, which can also be clinically manifested by suicidal behavior as well. Tricyclic antidepressants particularly of imipramine and clomipramine can have pro-suicidal effect, which is believed to be the consequence of their own hypothetic asynchronous cognitive psychomotor pharmacodynamic action. Antidepressants from the group of selective serotonin reuptake inhibitors can at the beginning of administration as monotherapy also have pro-suicidal effects in patients with hints of suicidality or suicidal behavior, by increasing the intensity of already present suicidal predictors, such as dysphoria, anxiety, impulsiveness, agitation etc. Antipsychotics can act stimulatingly upon predictors of suicidal behavior, that is, pro-suicidal in an indirect way through side effects they cause indirect pro suicidal neurological and consecutive psychological impact, as it is called. It is particularly valid for classic antipsychotics causing primarily neurological, i.e. extrapyramidal side effects, along which consecutive psychological side effects can occur as well. However, new antipsychotics in comparison to classic ones, have less pronounced neurological, extrapyramidal symptoms and signs but more somatic-metabolic side effects, and thereby their action can be mostly manifested as indirect pro-suicidal neurological and somatic-metabolic as well as consecutive psychological activity. PMID- 20305597 TI - Can we prevent blood dyscrasia (leucopenia, thrombocytopenia) and epileptic seizures induced by clozapine. AB - Clozapine is associated with various haematological adverse effects, including leukopenia, neutropenia, agarnulocytosis, leukocytosis, anaemia, eosinophilia, thrombocytopenia and thrombocythaemia. Recognition and treatment of clozapine related seizures also will become increasingly important as clozapine use grows in the 1990s. The decision to stop clozapine as a result of haematological adverse effects or seizures is a frustrating one for the clinician, and frequently disastrous for the patient. Cessation of treatment results in relapse. In case that patient is unresponsive to other antipsychotic, restarting clozapine should be consider, despite the risk involved. As the risk of a second agranulocytosis is much higher in those patients, various methods of militating against repeat blood dyscrasias have been treated, including granulocyte colony stimulating factor and lithium. The decision to restart clozapine should be taken on case-by-case basis and should take into account the likely risks and benefits of restarting. Prior response to clozapine and magnitude of patient deterioration on stopping treatment are important factors to take into this consideration. Clozapine-related seizures did not preclude successful treatment with clozapine. A strategy that has been proposed to reduce the occurrence of seizures is the addition of an anticonvulsant agent. However, clozapine does induce a variety of adverse effects, most of which are of limited duration and either preventable or manageable if a number of simple clinical procedures are followed. With careful haematologyc control, the risk of agranulocytosis can be minimized and in case of clozapine related seizures recommendations include dose reduction, electroencephalogram (EEG), plasma-level monitoring and prophylactic antiepileptic treatment. Re-exposure to clozapine may rarely be attempted where there are facilities for very close and frequent monitoring. PMID- 20305598 TI - Side effects of treatment with benzodiazepines. AB - BACKGROUND: The use of benzodiazepine anxiolytics and hypnotics continues to excite controversy. Views differ from expert to expert and from country to country as to the extent of the problem, or even whether long-term benzodiazepine use actually constitutes a problem. Although as a class benzodiazepines act rapidly and are well tolerated, their use presents clinical issues such as dependence, rebound anxiety, memory impairment, and discontinuation syndrome. The aim of this article is to review literature regarding different side effects associated with treatment with benzodiazepines - effects on cognition, treatment with benzodiazepines during pregnancy, dependence on benzodiazepines and risk of falling. CONTENT ANALYSIS OF LITERATURE: Literature research included structured searches of Medline and other publications on the subject of treatment with benzodiazepines, particularly effects on cognition, risk of falls, benzodiazepine dependence and treatment with benzodiazepines during pregnancy. CONCLUSION: Results of investigations have revealed different side effects associated with treatment with benzodiazepines. Previous investigations showed that treatment with benzodiazepines may induce anterograde amnesia. Also, previous studies confirmed occurrence of physical dependence in high percentage of patients in long term treatment with benzodiazepines at therapeutic dosages. Some investigation suggested higher risk of oral cleft, the floppy infant syndrome, or marked neonatal withdrawal symptoms when using benzodiazepines during pregnany. Investigations have shown increased risk of falling in elderly persons taking benzodiazepines. PMID- 20305599 TI - Othello syndrome in patients with Parkinson's disease. AB - BACKGROUND: Othello syndrome (OS) is an organic delusional disorder with prevailing jealousy symptoms presumably appearing as side effect of antiparkinsonian therapy. The clinical spectrum of psychiatric symptoms in Parkinson's disease (PD) is very wide, including symptoms of depression and anxiety, hallucinations, delusions, with prevalent paranoid symptoms, agitation, delirium and sleep disorders. At our knowledge, just a few cases of patients with PD and OS were reported till now. METHODS: three neurologists working in a tertiary referral centre were asked to report cases of pathological jealousy as defined by the DSM IV criteria (Kaplan et al. 1994). The following data were collected retrospectively: sex, age at PD onset, age at OS onset, duration of PD, duration of PD treatment, duration of treatment with dopamine agonists (DAs), treatment of OS, past history of alcoholism, premorbid personality disorder, family history of psychiatric disorders and data about general cognitive condition. RESULTS: Five PD patients (three males) with OS were investigated. The mean age of the patients at the PD onset was 46.80+/-8.87 (SD), the mean age at the OS onset was 56.40+/-8.76 (SD). Before the onset of OS, all of them were taking dopamine agonists. The first patient was treated with pramipexole, apomorphine infusion and levodopa/carbidopa, the second with apomorphine infusion plus levodopa/carbidopa/entacapone, the third with pramipexole, the fourth and fifth with ropinirole. Decrease of dopamine agonist led to clinical improvement in three patients (complete reduction of the symptoms in two, reduction of symptoms in one patients). In two patients, the symptoms remained the same. In three patients atypical neuroleptics had to be added: clozapine in two and quetiapine in one patient. CONCLUSIONS: We believe that OS is a more common psychiatric side effect in PD patients on treatment with dopamine agonists than usually believed, particulary in those with early disease onset. It is a very disturbing symptom for patients and their partners, often underestimated by them, and should therefore be actively searched for. PMID- 20305600 TI - Side-effects of generic. AB - New trends in medicine which are much more oriented towards pharmacoeconomy, are ever so common these days. There's an aim within the focus of the health system which is cutting down treatment expenses, and that relates to psychiatry practice too. Prescription drugs issued by specialist doctors are allowed to be switched with cheaper ones of the same group of drugs by GP doctors, with an aim of cost reduction. "Instead of the medicament prescribed, a GP doctor is allowed to prescribe an alternative medicament of the same efficacy in the dosage of an adequate strength" (taken from the specialist medical report form). A 74 years old man is treated for psychotic depression. Exogenic environmental factors caused the symptoms manifestation due to which hospitalization in a psychiatric ward occurred in two incidences. At the risperidone introduction soon after the second hospitalization event, a long term remission was obtained which lasted for several years. Despite a stable dose of psychopharmacs, new episode of the illness occurred. Researching the potential factors which lead towards the aggravation of the course of the illness disclosed that instead of the original risperidone, the pharmacist issued a generic in an equivalent dose. PMID- 20305601 TI - Valid grounds for the switch of original antipsychotics with generics. AB - Patients' non-compliance in treatments, such as irregular taking of medication, represents an enormous problem with psychiatric patients in general. This difficulty occurs especially in patients suffering from chronic mental illnesses such as schizophrenia. There are not any significant differences in the efficacy of reducing the positive symptoms in schizophrenia between the conventional and the atypical antipsychotics. However, the effects which are manifested in negative schizophrenia symptoms or in the patients' cognitive functioning, favour the atypical antipsychotics. When it comes to adding the subjective well-being of the patients and their improvement of the quality of life, then, the advantages of atypical antipsychotics are unquestionable. New trends in medicine are increasingly impinge on the pharmacoeconomy, which aims at reducing treatment cost. This trend is getting progressively stronger in the world and as such, it certainly will not bypass Croatia. Pharmacists and General Practice doctors (GP) are permitted, by the law, to replace the original medicament prescribed by a specialist doctor, with a cheaper one from the same generic group of medicaments, with a purpose of cutting down the treatment costs. Is there always a valid justification for such practice, and should it become a rule for all the patients out there? This is a case report of a patient who suffers from paranoid schizophrenia. He has been on a treatment with atypical antipsychotics and has kept in a good and stable remission for the past seven years. His therapy consisted of olanzapine in a dose of 15 mg in the evening, throughout the whole period of his 7-year remission. A month ago, his GP doctor self- initially prescribed a generic olanzapine. The impact of this decision on to the mental state of the patient as well as his trust in the treatment itself is described in this report. PMID- 20305602 TI - Antipsychotic side-effect - potential risk of patients rejecting their treatments. AB - Antipsychotics side-effects pose an enormous problem in psychiatric treatment. The choice of antipsychotics is a crucial issue in the treatment as both patients' cooperation and compliance often depend upon it. Severe side-effects might sometimes cause the treatment interruption, to which each patient is entitled. Schizotypal personality disorder (SPD) features include social and interpersonal deficits, discomfort with close relationships, as well as cognitive and perceptual distortions and eccentricities of behaviour. Dominant symptoms often determine psycho pharmacotherapy and therefore antipsychotic treatment is possible. A 23 year-old man was treated for 4 months due to disturbances typical for SPD. Since the patient did not respond well to haloperidol, zuclopenthixol was advised. The latter medication produced severe, life-threatening side-effects which caused urgent hospitalisation. Althouth zuclopenthixol was instantly retracted from the therapy, the patient and his family rejected any further psychiatric treatment. In spite the fact that hetero-data obtained from his mother a few months later, revealed disturbances which greatly affected the patient's live, the patient showed resistance to further psychiatric treatment because of his negative experience with this medication. PMID- 20305603 TI - The influence of side effect of antipsychotic on the course of treatment in adolescent. AB - The use of antipsychotics in treatment of children and adolescents requires good knowledge of psychopathology, psychofarmacotherapy, developmental processes and family relations. It is necessary to have parental consent for the use of a medication in this age, with previous explanation of therapeutic goals, limitations and possible side effects of antipsychotics. The number of antipsychotics registered for use in children and adolescents is quite limited. The combination of clinical experience of those working with psychotic adolescents and a good collaboration with parents, creates a therapeutic space where good results in treatment can be achieved. Side effects, though rarely, can bring in question the course of treatment and disorder follow up. In this work we will present a 14-year old girl adolescent with psychotic symptoms, in which case the course of treatment and discontinuance of therapy was caused by a side effect - an oculogyric crisis. PMID- 20305604 TI - The role of CYP2D6 and TaqI A polymorphisms in malignant neuroleptic syndrome: two case reports with three episodes. AB - Malignant neuroleptic syndrome (MNS) is a serious and potentially fatal side effect of neuroleptic treatment. Beside antipsychotic drugs, other psychotropic drugs such as antidepressants and lithium carbonate can cause this life threatening side-effect. Underlying mechanism of this side-effect is still unknown and debated. So far some risk factors have been identified, with clinical observations and recent pharmacogenetic research suggesting (with inconsistent findings) correlation between genetic mechanisms and predisposition to MNS. Polymorphisms of CYP2D6 enzyme through which most psychotropic drugs are metabolized and TaqIA DRD2 which is target for antipsychotic drugs could be the link between pharmacogenetic factors and potential for development of MNS. In this paper we present two case reports with clinical presentation of three consecutive MNS. One patient developed MNS while he was taking combination of drugs: first time haloperidol, promazine and fluphenazine, second time fluphenazine and perazine and third time clozapine, promazine and valproic acid consecutively. The other patient developed MNS while taking following combination of drugs: first time haloperidol and lithium carbonate, second time risperidone and third time clozapine consecutively. Pharmacogenetic analysis for CYP2D6 and TaqI A DRD2 polymorphisms for both patients was done. Genotypisation of CYP2D6*1*3*4*5*6 in both patients showed no evidence of poor metabolizer phenotype. On the other hand, first patient was heterozygous for CYP2D6*4 (genotype *1/*4). CYP2D6 polymorphisms could have clinical significance because may lead to toxicity and unwanted side-effects in standard usual antipsychotic dose ranges. Analysis Taql A DRD2 polymorphism for first patient showed that he is heterozygous for A1 allele (genotype A1A2) which is commonly associated with predisposition to MNS. According to our literature three consecutive MNS are rarely described, and incidence of MNS generally is too low to perform clinical research. Many patophysiological mechanisms may probably underlie this complex and potentially fatal syndrome, still unknown etiology. But, genetic mechanisms could be significant. Further pharmacogenetic research, findings and analysis in patients who develop single or repeated MNS are strongly recommended. In long term, pharmacogenetic analysis, implemented in daily clinical practice, could help in prevention of this extremely serious side-effect. PMID- 20305605 TI - Ziprasidone as a possible cause of cleft palate in a newborn. AB - Use of antipsychotic medication during the entire course of pregnancy in patients suffering from schizophrenia is frequently necessary as discontinuation of therapy can lead to relapse of the illness which can be far more severe for the mother, but also for the fetus. That is the case why third generation antipsychotics, so called atypical antipsychotics, are also being used during the pregnancy, but their effects are not fully researched. Use of ziprasidone as a third generation antipsychotic, and its effects during the pregnancy in patients suffering from various mental illnesses is very rarely described in scientific literature. There is even fewer information regarding eventual adverse events of ziprasidone in newborn babies of mothers that have been treated with ziprasidone during the entire course of pregnancy. This paper will be based around a case report of a female patient suffering from schizophrenia who has been treated with ziprasidone during the entire course of her pregnancy and whose newborn baby was diagnosed with a cleft palate (palatoschisis) at the time of birth. PMID- 20305606 TI - Hyperprolactinaemia - a risperidone side-effect. AB - A 47 year old patient has been treated for psychotic depression for the last 5 years. The illness began manifesting through the symptoms of depressive thoughts, intrapsychic tension, projectivity, derealisation phenomena and pre-psychotic fears. She was treated with a combination of antidepressives, anxiolitics and hypnotics in ambulatory conditions. The therapy applied did not obtain the effects expected due to which an atypical antipsychotic was administered subsequently - risperidone, a 2 mg dose in the evening. After commencing the antipsychotic treatment, the symptoms started to weaken and a steady remission was obtained. Two years after a regular risperidone administration (in combination with fluoxetine, alprazolam and flurazepam) the patient reported some "bleeding" in October 2006. Hormonal blood tests were performed and high prolactin values were registered (2567.0 mIJ/L),due to which a gradual risperidone retractement was indicated. Medicamentous hyperprolactinaemia is a well known side effect of risperidone. A gradual risperidone retractement lead to a lowered and normal prolactin level within a month. PMID- 20305607 TI - Amenorrhoea - consequence of combined treatment with sulpiride and risperidone in a patient suffering from schizophrenia. AB - It is well documented that sulpiride causes hormonal adverse events, like amenorrhoea and galactorrhea, due to its mechanism of action. Furthermore, risperidone can produce amenorrhoea and galactorrhea also, due to its mechanism of action, which differs from that of sulpiride. This case report is of a patient that was treated with large doses of sulpiride, but did not develop an adverse event like amenorrhoea. However, when risperidone was introduced into therapy it leads to the onset of amenorrhoea. Gynecologist saw it as the beginning of menopause. General practitioner questioned the existence of an intra-cerebral process that could produce amenorrhoea as well. Therefore, the patient was sent to perform an MRI of the brain, under work diagnosis of pituitary adenoma, which was later ruled out as a cause of the illness. Well experienced psychiatrist linked the loss of menstruation with the adverse event profile of sulpiride and therefore gradually discontinued sulpiride from therapy, while risperidone was left and subsequently menstrual cycle was restored. Good knowledge of adverse events profile of antipsychotic medication used, especially when used in a combination, allows us to correctly question appearance of adverse events, to adequately treat them and lowers the cost of unneeded medical procedures. PMID- 20305608 TI - Galactorrhea - side effect of risperidone in combination with depakine chrono in a patient with bipolar disorder. AB - Risperidone, as all atypical antipsychotics, can cause hyperprolactinemia which can in turn lead to galactorrhea. Mood stabilizers, one of which is valproic acid and its derivate "Depakine Chrono", are rarely linked with symptomatic hyperprolactinemia and do not alter prolactin concentrations. This case is based around a patient suffering from a bipolar disorder that has been psychiatrically treated in an outpatient clinic during four years. Bipolar disorder treatment was started with carbamazepine, but later it was discontinued due to adverse events and extreme increase of liver transaminases. Treatment was continued with introduction of lithium, but the patient stated that she could not tolerate it. Subsequently, her endocrinologist advised for lithium discontinuation due to very severe osteoporosis. At the beginning of 2009, lithium was discontinued and Depakine Chrono was introduced. Due to patient's psychotic decompensation it was necessary to introduce risperidone into treatment and soon afterwards her psychotic symptoms settled. After several months of treatment her mood lowered, she began to feel sedated, psychomotorically retarded and that lead to dose lowering of Depakine Chrono and risperidone, at which point galactorrhea as a serious adverse event occurred. Occurrence of galactorrhea at lower risperidone doses in this case might be partially explained by recent studies that showed that lower doses of risperidone can also improve psychic state, but could also cause adverse events. Although galactorrhea, as a direct consequence of hyperprolactinemia caused by risperidone has mainly been researched with higher doses of this atypical antipsychotic, we have to keep in mind that lower doses could also cause serious adverse events. PMID- 20305609 TI - Ejaculatory dysfunction in patient with schizophrenia on sertindole. AB - The antipsychotic drugs can be of great benefit for the wide range of psychotic disorders, but all are associated with various adverse effects. Patients with psychotic disorder consider the sexual dysfunction to be among the most important side effects. Although, it is not uncommon for the patients with schizophrenia to report the sexual dysfunction, patients with untreated schizophrenia have fewer dysfunctions compared to those on antipsychotic medication. The decision whether the current treatment with a prolactin-increasing antipsychotic or sexual dysfunction inducing drug should be continued or switched to another antipsychotic drug, has to be made on the basis of the patient's risk-benefit estimation. It has to be kept on mind that adverse effects are usually dose dependent. In this case report, sertindole treated patient with chronic schizophrenia developed sexual side effect manifested as ejaculatory dysfunction that was significantly ameliorated by drug-dose reduction. PMID- 20305610 TI - Infection or idiosyncratic reaction to antiepileptic drugs? AB - Idiosyncratic reactions are serious, unpredicted adverse effects of antiepileptic drugs which are in use in psychiatry as mood stabilizers. Severe idiosyncratic reactions can manifest as systemic symptoms or Dress syndrome clinically manifested with increased body temperature, peripheral lymphadenopathy and potential one or multiple organ failure. We present a 36 years old patient, who was hospitalized for the first time in our hospital after he attempted suicide by hanging. Patient was diagnosed as Bipolar affective disorder, current episode depressive with psychotic features and high suicidal risk. At the time of admission he was taking olanzapine and venlafaxine. Psychopharmacs were cross titrated to clozapine, valproic acid and lamotrigine. Two weeks later, patient's mood was stabilized but his somatic status worsened dramatically. He was forwarded to Clinic for Infective Diseases where he was diagnosed with severe sepsis. Dress syndrome, although initially suspected was not verified, but has to be taken into consideration in each patient prescribed with antiepileptic drugs. PMID- 20305611 TI - The effects of cardiac surgical procedures on health - related quality of life, cognitive performance, and emotional status outcomes: a prospective 6 - month follow - up study. AB - INTRODUCTION: The aim of this study was to assess the course of health - related quality of life, cognitive and emotional change during the six months after elective CABG, and to investigate how cognitive impairments, depression and posttraumatic stress symptoms were related to quality of life. METHOD: In a prospective study, we followed up for 6 months 138 of the original 147 patients who had undergone elective CABG surgery. CONCLUSION: Elective CABG is associated with significant improvements in HRQOL relative to the preoperative period, but impairments in HRQOL were found in a subgroup of post - CABG patients with evidence of PTSD, depression, or cognitive impairments at 6 - month follow - up. PMID- 20305612 TI - in-vivo detection of protein-protein interactions on micro-patterned surfaces. AB - Unraveling the interaction network of molecules in-vivo is key to understanding the mechanisms that regulate cell function and metabolism. A multitude of methodological options for addressing molecular interactions in cells have been developed, but most of these methods suffer from being rather indirect and therefore hardly quantitative. On the contrary, a few high-end quantitative approaches were introduced, which however are difficult to extend to high throughput. To combine high throughput capabilities with the possibility to extract quantitative information, we recently developed a new concept for identifying protein-protein interactions (Schwarzenbacher et al., 2008). Here, we describe a detailed protocol for the design and the construction of this system which allows for analyzing interactions between a fluorophore-labeled protein ("prey") and a membrane protein ("bait") in-vivo. Cells are plated on micropatterned surfaces functionalized with antibodies against the bait exoplasmic domain. Bait-prey interactions are assayed via the redistribution of the fluorescent prey. The method is characterized by high sensitivity down to the level of single molecules, the capability to detect weak interactions, and high throughput capability, making it applicable as screening tool. PMID- 20305613 TI - Hydrophilic polymer emboli: an under-recognized iatrogenic cause of ischemia and infarct. AB - With the increased use of percutaneous intravascular diagnostic and therapeutic devices, there is potential for embolization of materials introduced into the vasculature. We report nine cases of foreign body emboli in patients who underwent vascular procedures using hydrophilic-coated medical devices. The procedures performed included cardiac catheterization (four cases), diagnostic cerebral angiography (two cases), therapeutic cerebral angiography with coil embolization of intracerebral aneurysm (one case), lower extremity angiography (one case), and/or orthotopic cadaveric organ transplantation (three cases). Other procedures in these patients included hemodialysis and peripheral arterial or central venous catheterization. Clinical sequelae ranged from undetectable (no symptoms) to pulmonary infarction, stroke, ongoing gangrene, and/or death occurring within days to weeks of suspected embolization of foreign material. Microscopic findings in biopsy or autopsy tissue revealed aggregates of amorphous or lamellated, non-refractile, non-polarizable, predominantly basophilic foreign substances occluding intrapulmonary, intracerebral, or peripheral arteries. This is the largest series documenting embolization of polymer gel materials. Polymer gel is now widely used on several devices for interventional procedures worldwide, and we suspect that complications associated with iatrogenic embolization of this substance are under-recognized. PMID- 20305614 TI - Reduced expression of SMARCB1/INI1 protein in synovial sarcoma. AB - Synovial sarcoma is classified as a tumor of uncertain differentiation, and some synovial sarcomas have rhabdoid cells. In previous studies, all malignant rhabdoid tumors and renal medullary carcinomas, some extraskeletal myxoid chondrosarcomas, almost all epithelioid sarcomas and half of epithelioid malignant peripheral nerve sheath tumors showed a loss of SMARCB1/INI1 protein expression in tumor cells and all of these tumors are also known to have rhabdoid cells. We analyzed the immunohistochemical and mRNA expression of SMARCB1/INI1 in 95 synovial sarcomas (73 monophasic fibrous type, 18 biphasic type and 4 poorly differentiated type) and 30 spindle cell sarcomas (3 adult fibrosarcomas, 7 fibrosarcomas arising in dermatofibrosarcoma protuberans, 10 leiomyosarcomas and 10 malignant peripheral nerve sheath tumors) resembling monophasic fibrous synovial sarcoma. The results have shown that 66 of the 95 synovial sarcoma cases (69%) had reduced SMARCB1/INI1 protein expression, whereas the remaining 29 cases (31%) and all 30 spindle cell sarcomas showed preserved this protein expression. No case with a complete loss of SMARCB1/INI1 protein expression was recognized. The median values of SMARCB1/INI1 mRNA expression in non-tumor skeletal muscle and synovial sarcoma with reduced protein expression were 12.86 and 134.01, respectively, and a statistically significant difference was detected between these two groups (P=0.0000004). However, there was no statistically significant difference of prognosis between the synovial sarcoma group with reduced and that with preserved SMARCB1/INI1 protein expression (P=0.46). Therefore, it was suggested that there is a post-transcriptional SMARCB1/INI1 regulatory mechanism in the tumor cells of synovial sarcoma. PMID- 20305615 TI - Warty-basaloid carcinoma: clinicopathological features of a distinctive penile neoplasm. Report of 45 cases. AB - Most penile cancers are squamous cell carcinomas, but there are several subtypes with different clinicopathologic, viral, and outcome features. We are presenting 45 cases of a distinctive morphological variant of penile squamous cell carcinoma composed of mixed features of warty and basaloid carcinomas. This tumor was earlier recognized in a recent viral study and showed a high association with human papillomavirus infection. However, clinicopathologic features are not well known. In this multi-institutional study, patients' mean age was 62 years. Most tumors (64%) invaded multiple anatomical compartments, including glans, coronal sulcus, and, especially, inner foreskin mucosa. Tumor size ranged from 2 to 12 cm (mean 5.5 cm). Three morphological patterns were recognized: (1) the most common, observed in two-thirds of the cases was that of a typical condylomatous tumor on surface and basaloid features in deep infiltrative nests; (2) in 15% of the cases, there were non-papillomatous invasive carcinoma nests with mixed basaloid and warty features; and (3) unusually, predominantly papillomatous. Invasion of penile erectile tissues was frequent, either corpus spongiosum or cavernosum (47% each). Tumors limited to lamina propria were rare. Most tumors were of high grade (89%). Vascular and perineural invasion were found in about one-half and one quarter of cases, respectively. Associated penile intraepithelial neoplasia was identified in 19 cases and mostly showed basaloid, warty-basaloid, or warty features. Inguinal nodal metastases were found in 11/21 patients with groin dissections. Invasion of corpora cavernosa, high histological grade, and presence of vascular/perineural invasion were more prevalent in metastatic cases. In 21 patients followed, the cancer-specific mortality rate was 33% with a mean survival time of 2.8 years. Warty-basaloid carcinomas are morphologically distinctive human papillomavirus-related penile neoplasms that, such as basaloid carcinomas, are biologically more aggressive than typical warty carcinoma from which they should be distinguished. PMID- 20305616 TI - Pancreatic endocrine tumors: improved TNM staging and histopathological grading permit a clinically efficient prognostic stratification of patients. AB - Pancreatic endocrine tumors are rare diseases and devising a clinically effective prognostic stratification of patients is a major clinical challenge. This study aimed at assessing whether the tumor-node-metastasis (TNM)-based staging and proliferative activity-based grading recently proposed by the European NeuroEndocrine Tumors Society (ENETS) have clinical value. TNM was applied to 274 patients with histologically diagnosed pancreatic endocrine tumors operated from 1991 to 2005, with last follow-up at December 2007. According to World Health Organization (WHO) classification, 246 were well-differentiated neoplasms (51 benign, 56 uncertain behavior, 139 carcinomas) and 28 poorly differentiated carcinomas. Grading was based on Ki67 immunohistochemistry. Survival analysis not only ascertained the prognostic value of the TNM system but also highlighted that in the absence of nodal and distant metastasis, infiltration and tumor dimensions over 4 cm had prognostic significance. T parameters were then appropriately modified to reflect this weakness. The 5-year survival for modified TNM stages I, II, III and IV were 100, 93, 65 and 35%, respectively. Multivariate analysis identified TNM stages as independent predictors of death, in which stages II, III and IV showed a risk of death of 7, 29 and 58 times higher than stage I tumors (P<0.0001). Ki67-based grading resulted an independent predictor of survival with cut-offs at 5 and 20%. In conclusion, WHO classification assigns clinically significant diagnostic categories to pancreatic endocrine tumors that need prognostic stratification by applying a staging system. The ENETS-TNM provides the best option, but it requires some modifications to be fully functional. The modified TNM described in this study ameliorates the clinical applicability and prediction of outcome of the ENETS-TNM; it (i) assigns a risk of death proportional to the stage at the time of diagnosis, and (ii) allows a clinically based staging of patients, as the T parameters as modified permit their clinical radiological recognition. Ki67-based grading discerns prognosis of patients with same stage diseases. PMID- 20305617 TI - Alternate mucoid and hyalinized stroma in clear cell carcinoma of the ovary: manifestation of serial stromal remodeling. AB - The stroma in ovarian clear cell carcinoma often shows alternate mucoid and hyalinized change. The hyalinized stroma is recognized to be an aberrant deposition of basement membrane material produced by tumor cells. The mucoid stroma, however, has drawn far less attention, and its significance remains unclear. We examined 60 ovarian clear cell carcinomas for the distribution and nature of the mucoid stroma. For comparison, 125 other surface epithelial ovarian tumors were examined. Twenty-nine of 60 (48%) clear cell carcinomas showed a mucoid stroma, either focally (21 cases) or diffusely (8 cases). The mucoid stroma in clear cell carcinomas was distinct from that in other surface epithelial tumors as follows: it showed a compact spherule-like appearance, commonly occupying the cores of small papillae. It also exhibited a cribriform pattern, resembling that of adenoid cystic carcinoma. It was rarely associated with stromal cells, despite the presence of abundant glycosaminoglycan including hyaluronan. Alternatively, it was strongly associated with hyalinized stroma. Among 40 clear cell carcinomas that had at least one type of stroma, 26 (65%) had both, either concomitantly or separately. The mucoid stroma tended to attenuate if the hyalinized stroma developed. In vitro, a clear cell carcinoma cell line, HAC-2, formed a spherule-like structure containing hyaluronan in the center, and a significant amount of hyaluronan was detected by latex agglutination immunoturbidimetry, indicating that HAC-2 itself has the potential to produce hyaluronan. All of these facts indicate that the spherule-like mucoid stroma and hyalinized stroma represent different phases of the stromal remodeling process, which is promoted by the deposition of different extracellular matrices produced by clear cell carcinoma cells. The spherule-like mucoid stroma and hyalinized stroma are considered complementary diagnostic signatures of ovarian clear cell carcinoma. PMID- 20305618 TI - Endometrial and ovarian carcinomas with undifferentiated components: clinically aggressive and frequently underrecognized neoplasms. AB - Carcinomas of the endometrium and ovary with undifferentiated components are uncommon neoplasms that are likely underdiagnosed. They are important to recognize as they have been shown to be clinically aggressive. We identified 32 carcinomas with undifferentiated components as defined by Silva and co-workers, 26 endometrial and 6 of ovarian origin. The patient age ranged from 21 to 76 years (median 55); 40% of patients were or=200 regulatory proteins to form highly specific holoenzymes. These regulatory proteins target PP1 to its point of action within the cell and prime its enzymatic specificity for particular substrates. However, how they direct PP1's specificity is not understood. Here we show that spinophilin, a neuronal PP1 regulator, is entirely unstructured in its unbound form, and it binds PP1 through a folding-upon-binding mechanism in an elongated fashion, blocking one of PP1's three putative substrate binding sites without altering its active site. This mode of binding is sufficient for spinophilin to restrict PP1's activity toward a model substrate in vitro without affecting its ability to dephosphorylate its neuronal substrate, glutamate receptor 1 (GluR1). Thus, our work provides the molecular basis for the ability of spinophilin to dictate PP1 substrate specificity. PMID- 20305657 TI - Self-poisoning of Mycobacterium tuberculosis by targeting GlgE in an alpha-glucan pathway. AB - New chemotherapeutics are urgently required to control the tuberculosis pandemic. We describe a new pathway from trehalose to alpha-glucan in Mycobacterium tuberculosis comprising four enzymatic steps mediated by TreS, Pep2, GlgE (which has been identified as a maltosyltransferase that uses maltose 1-phosphate) and GlgB. Using traditional and chemical reverse genetics, we show that GlgE inactivation causes rapid death of M. tuberculosis in vitro and in mice through a self-poisoning accumulation of maltose 1-phosphate. Poisoning elicits pleiotropic phosphosugar-induced stress responses promoted by a self-amplifying feedback loop where trehalose-forming enzymes are upregulated. Moreover, the pathway from trehalose to alpha-glucan exhibited a synthetic lethal interaction with the glucosyltransferase Rv3032, which is involved in biosynthesis of polymethylated alpha-glucans, because key enzymes in each pathway could not be simultaneously inactivated. The unique combination of maltose 1-phosphate toxicity and gene essentiality within a synthetic lethal pathway validates GlgE as a distinct potential drug target that exploits new synergistic mechanisms to induce death in M. tuberculosis. PMID- 20305658 TI - Glycopeptide-specific monoclonal antibodies suggest new roles for O-GlcNAc. AB - Studies of post-translational modification by beta-N-acetyl-D-glucosamine (O GlcNAc) are hampered by a lack of efficient tools such as O-GlcNAc-specific antibodies that can be used for detection, isolation and site localization. We have obtained a large panel of O-GlcNAc-specific IgG monoclonal antibodies having a broad spectrum of binding partners by combining three-component immunogen methodology with hybridoma technology. Immunoprecipitation followed by large scale shotgun proteomics led to the identification of more than 200 mammalian O GlcNAc-modified proteins, including a large number of new glycoproteins. A substantial number of the glycoproteins were enriched by only one of the antibodies. This observation, combined with the results of inhibition ELISAs, suggests that the antibodies, in addition to their O-GlcNAc dependence, also appear to have different but overlapping local peptide determinants. The monoclonal antibodies made it possible to delineate differentially modified proteins of liver in response to trauma-hemorrhage and resuscitation in a rat model. PMID- 20305659 TI - Capture of influenza by medullary dendritic cells via SIGN-R1 is essential for humoral immunity in draining lymph nodes. AB - A major pathway for B cell acquisition of lymph-borne particulate antigens relies on antigen capture by subcapsular sinus macrophages of the lymph node. Here we tested whether this mechanism is also important for humoral immunity to inactivated influenza virus. By multiple approaches, including multiphoton intravital imaging, we found that antigen capture by sinus-lining macrophages was important for limiting the systemic spread of virus but not for the generation of influenza-specific humoral immunity. Instead, we found that dendritic cells residing in the lymph node medulla use the lectin receptor SIGN-R1 to capture lymph-borne influenza virus and promote humoral immunity. Thus, our results have important implications for the generation of durable humoral immunity to viral pathogens through vaccination. PMID- 20305660 TI - Myeloperoxidase acts as a profibrotic mediator of atrial fibrillation. AB - Observational clinical and ex vivo studies have established a strong association between atrial fibrillation and inflammation. However, whether inflammation is the cause or the consequence of atrial fibrillation and which specific inflammatory mediators may increase the atria's susceptibility to fibrillation remain elusive. Here we provide experimental and clinical evidence for the mechanistic involvement of myeloperoxidase (MPO), a heme enzyme abundantly expressed by neutrophils, in the pathophysiology of atrial fibrillation. MPO deficient mice pretreated with angiotensin II (AngII) to provoke leukocyte activation showed lower atrial tissue abundance of the MPO product 3 chlorotyrosine, reduced activity of matrix metalloproteinases and blunted atrial fibrosis as compared to wild-type mice. Upon right atrial electrophysiological stimulation, MPO-deficient mice were protected from atrial fibrillation, which was reversed when MPO was restored. Humans with atrial fibrillation had higher plasma concentrations of MPO and a larger MPO burden in right atrial tissue as compared to individuals devoid of atrial fibrillation. In the atria, MPO colocalized with markedly increased formation of 3-chlorotyrosine. Our data demonstrate that MPO is a crucial prerequisite for structural remodeling of the myocardium, leading to an increased vulnerability to atrial fibrillation. PMID- 20305661 TI - The Mycobacterium tuberculosis protein LdtMt2 is a nonclassical transpeptidase required for virulence and resistance to amoxicillin. AB - The peptidoglycan layer is a vital component of the bacterial cell wall. The existing paradigm describes the peptidoglycan network as a static structure that is cross-linked predominantly by 4-->3 transpeptide linkages. However, the nonclassical 3-->3 linkages predominate the transpeptide networking of the peptidoglycan layer of nonreplicating Mycobacterium tuberculosis. The molecular basis of these linkages and their role in the physiology of the peptidoglycan layer, virulence and susceptibility of M. tuberculosis to drugs remain undefined. Here we identify MT2594 as an L,D-transpeptidase that generates 3-->3 linkages in M. tuberculosis. We show that the loss of this protein leads to altered colony morphology, loss of virulence and increased susceptibility to amoxicillin clavulanate during the chronic phase of infection. This suggests that 3-->3 cross linking is vital to the physiology of the peptidoglycan layer. Although a functional homolog exists, expression of ldtMt2 is dominant throughout the growth phases of M. tuberculosis. 4-->3 transpeptide linkages are targeted by one of the most widely used classes of antibacterial drugs in human clinical use today, beta lactams. Recently, meropenem-clavulanate was shown to be effective against drug resistant M. tuberculosis. Our study suggests that a combination of L,D transpeptidase and beta-lactamase inhibitors could effectively target persisting bacilli during the chronic phase of tuberculosis. PMID- 20305662 TI - Pleiotrophin regulates the expansion and regeneration of hematopoietic stem cells. AB - Hematopoietic stem cell (HSC) self-renewal is regulated by both intrinsic and extrinsic signals. Although some of the pathways that regulate HSC self-renewal have been uncovered, it remains largely unknown whether these pathways can be triggered by deliverable growth factors to induce HSC growth or regeneration. Here we show that pleiotrophin, a neurite outgrowth factor with no known function in hematopoiesis, efficiently promotes HSC expansion in vitro and HSC regeneration in vivo. Treatment of mouse bone marrow HSCs with pleiotrophin caused a marked increase in long-term repopulating HSC numbers in culture, as measured in competitive repopulating assays. Treatment of human cord blood CD34(+)CDCD38(-)Lin(-) cells with pleiotrophin also substantially increased severe combined immunodeficient (SCID)-repopulating cell counts in culture, compared to input and cytokine-treated cultures. Systemic administration of pleiotrophin to irradiated mice caused a pronounced expansion of bone marrow stem and progenitor cells in vivo, indicating that pleiotrophin is a regenerative growth factor for HSCs. Mechanistically, pleiotrophin activated phosphoinositide 3-kinase (PI3K) signaling in HSCs; antagonism of PI3K or Notch signaling inhibited pleiotrophin-mediated expansion of HSCs in culture. We identify the secreted growth factor pleiotrophin as a new regulator of both HSC expansion and regeneration. PMID- 20305663 TI - Genetic variation in human HBB is associated with Plasmodium falciparum transmission. AB - Genetic factors are known to have a role in determining susceptibility to infectious diseases, although it is unclear whether they may also influence host efficiency in transmitting pathogens. We examine variants in HBB that have been shown to be protective against malaria and test whether these are associated with the transmission of the parasite from the human host to the Anopheles vector. We conducted cross-sectional malariological surveys on 3,739 human subjects and transmission experiments involving 60 children and 6,446 mosquitoes in Burkina Faso, West Africa. Protective hemoglobins C (HbC, beta6Glu-->Lys) and S (beta6Glu ->Val) are associated with a twofold in vivo (odds ratio 2.17, 95% CI 1.57-3.01, P = 1.0 x 10(-6)) and a fourfold ex vivo (odds ratio 4.12, 95% CI 1.90-9.29, P = 7.0 x 10(-5)) increase of parasite transmission from the human host to the Anopheles vector. This provides an example of how host genetic variation may influence the transmission dynamics of an infectious disease. PMID- 20305667 TI - Inflammation: extinguishing the fires within. PMID- 20305670 TI - How our growing understanding of inflammation has reshaped the way we think of disease and drug development. PMID- 20305664 TI - Rare genetic variation at Zea mays crtRB1 increases beta-carotene in maize grain. AB - Breeding to increase beta-carotene levels in cereal grains, termed provitamin A biofortification, is an economical approach to address dietary vitamin A deficiency in the developing world. Experimental evidence from association and linkage populations in maize (Zea mays L.) demonstrate that the gene encoding beta-carotene hydroxylase 1 (crtRB1) underlies a principal quantitative trait locus associated with beta-carotene concentration and conversion in maize kernels. crtRB1 alleles associated with reduced transcript expression correlate with higher beta-carotene concentrations. Genetic variation at crtRB1 also affects hydroxylation efficiency among encoded allozymes, as observed by resultant carotenoid profiles in recombinant expression assays. The most favorable crtRB1 alleles, rare in frequency and unique to temperate germplasm, are being introgressed via inexpensive PCR marker-assisted selection into tropical maize germplasm adapted to developing countries, where it is most needed for human health. PMID- 20305665 TI - The safety and side effects of monoclonal antibodies. AB - Monoclonal antibodies (mAbs) are now established as targeted therapies for malignancies, transplant rejection, autoimmune and infectious diseases, as well as a range of new indications. However, administration of mAbs carries the risk of immune reactions such as acute anaphylaxis, serum sickness and the generation of antibodies. In addition, there are numerous adverse effects of mAbs that are related to their specific targets, including infections and cancer, autoimmune disease, and organ-specific adverse events such as cardiotoxicity. In March 2006, a life-threatening cytokine release syndrome occurred during a first-in-human study with TGN1412 (a CD28-specific superagonist mAb), resulting in a range of recommendations to improve the safety of initial human clinical studies with mAbs. Here, we review some of the adverse effects encountered with mAb therapies, and discuss advances in preclinical testing and antibody technology aimed at minimizing the risk of these events. PMID- 20305671 TI - DNATwist: a Web-based tool for teaching middle and high school students about pharmacogenomics. AB - DNATwist is a Web-based learning tool (available at http://www.dnatwist.org) that explains pharmacogenomics concepts to middle- and high-school students. Its features include (i) a focus on drug responses of interest to teenagers (e.g., alcohol intolerance), (ii) reusable graphical interfaces that reduce extension costs, and (iii) explanations of molecular and cellular drug responses. In testing, students found the tool and topic understandable and engaging. The tool is being modified for use at the Tech Museum of Innovation in California. PMID- 20305672 TI - Is interleukin-6 receptor blockade the Holy Grail for inflammatory diseases? AB - Interleukin-6 (IL-6) has been linked to a myriad of diseases associated with inflammation, including rheumatoid arthritis (RA), Crohn's disease, and several types of cancer. In 2009 the US Food and Drug Administration accepted a complete response submission for the use of Actemra (tocilizumab), the first humanized IL 6 receptor-inhibiting monoclonal antibody, for the treatment of RA. Although this treatment will certainly help in managing inflammatory disorders such as RA, we suggest that side effects of such blockade may be excess weight gain and hyperlipidemia. PMID- 20305673 TI - Reporting of studies on new medicines in major medical journals: a case study in breast cancer. AB - A comparison of the results of pivotal trials on three new medicines for advanced breast cancer published in medical journals with those presented in the US Food and Drug Administration (FDA) reviews showed that analyses reported in journals were of lower quality and were given a favorable interpretation by minimizing toxicity and ignoring methodological shortcomings. Several proposals to strengthen the quality of reporting of clinical trials in medical journals and to support reliable assessment of the therapeutic value of new medicines are discussed. PMID- 20305674 TI - Relationship between insulin resistance, obesity and serum prostate-specific antigen levels in healthy men. AB - The purpose of this study was to determine the relationship between insulin resistance, obesity and serum prostate-specific antigen (PSA) levels in healthy men with serum PSA level below 4 ng mL(-1). The men included in the study cohort were 11 827 healthy male employees of the Korea Hydro and Nuclear Power Co., LTD who had undergone medical checkups including fasting glucose, fasting insulin and serum PSA between January 2003 and December 2008. Insulin resistance was calculated by homeostasis model assessment (HOMA [fasting glucose x fasting insulin]/22.5) and quantitative insulin sensitivity check index (QUICKI; 1/[log (fasting insulin) + log (fasting glucose)]). Age-adjusted body mass index (BMI) was significantly increased according to increasing quartile of insulin resistance as determined by HOMA and QUICKI, respectively, in analysis of variance (ANOVA) test and Duncan's multiple comparison test (P < 0.001), but age adjusted serum PSA concentration was significantly decreased according to increasing quartile of insulin resistance as determined by HOMA and QUICKI (P < 0.001). Age, BMI, insulin resistance by HOMA or QUICKI were significantly independent variables to serum PSA level in a multivariate linear regression analysis (P < 0.001). Insulin resistance was a significant independent variable to serum PSA level along with BMI. Insulin resistance and BMI were negatively correlated with serum PSA level in healthy men. Insulin resistance was positively correlated with BMI. PMID- 20305675 TI - Purinergic contraction of the rat vas deferens in L-NAME-induced hypertension: effect of sildenafil. AB - Hypertension (HTN) is a risk factor for erectile dysfunction, but its effect on vas deferens (VD) contractility and the ejaculatory response has not been delineated. NG-nitro-L-arginine methyl ester (L-NAME), a nitric oxide synthase inhibitor, was used for induction of nitric oxide (NO)-deficient HTN. Our aim was to evaluate the effects of L-NAME-induced HTN on rat VD contractility and to determine whether sildenafil affects VD contractility. A total of 36 male rats were divided into (1) control, (2) L-NAME-HTN, (3) sildenafil treated L-NAME-HTN groups. Group 2 was treated with L-NAME (40 mg kg(-1) per day) in drinking water for 4 weeks. Group 3 received sildenafil (1.5 mg kg(-1) per day, by oral gavage) concomitantly with L-NAME. The prostatic portion of the VD was subjected to electrical field stimulation (EFS, 1-20 Hz), and the P2X(1) agonist alpha,beta methylene ATP (alpha,beta-meATP, 100 micromol L(-1)-1 micromol L(-1)) and the alpha1-adrenoceptor agonist phenylephrine (Phe, 100 micromol L(-1)-1 mmol L(-1)) were used to construct concentration-response curves. These experiments were repeated in the presence of P2X receptor antagonist, pyridoxalphosphate-6 azophenyl-2',4'-disulfonic acid (PPADS, 30 micromol L(-1)). VD contractions in response to EFS, alpha,beta-meATP and Phe were significantly enhanced by L-NAME. Sildenafil treatment in the L-NAME group improved the contractile response of VD to EFS (20 Hz). In the presence of PPADS, the enhanced contractile response of VD to EFS and alpha,beta-meATP in hypertensive rats was reversed. In the rat model of chronic NO depletion, the purinergic and adrenergic components and EFS affect VD contractility. The VD contractile response may be mediated more by the purinergic system than the adrenergic system, and sildenafil may alter the ejaculatory response in men with PE. PMID- 20305676 TI - Isolated micropenis reveals partial androgen insensitivity syndrome confirmed by molecular analysis. AB - Partial androgen insensitivity syndrome (PAIS) is the milder variant of androgen receptor (AR) defects. The subtle effects of AR mutations present in a patient with micropenis, peno-scrotal hypospadias, infertility, clitoromegaly and posterior labial fusion. We studied the association of isolated micropenis with the genetic defects resulting in androgen resistance, that is, AR gene defects and 5-alpha reductase type 2 (SRD5A2) deficiency. We describe two cases of isolated micropenis: one in a 14-year-old boy and the other in a 3-year-old boy who was followed until he was 10 years old. There were no findings of hypospadias, cryptorchidism or gynecomastia in either of these patients. Serum gonadotrophin and androgen levels were obtained and karyotyping was done. Human chorionic gonadotropin (hCG) stimulation testing assessed the functional capacity of the testes. DNA was extracted from peripheral leukocytes, and all exons of the SRD5A2 and AR genes were amplified by polymerase chain reaction and sequenced. In both patients, baseline testosterone (T) level was low and the values were elevated after hCG testing. The sequence of the SRD5A2 gene was normal in patient 1, and a heterozygous polymorphism, V89L, was found in patient 2. Two known mutations, P390S and A870V, were identified in patients 1 and 2, respectively. Mutations in the AR gene can be associated with isolated micropenis without other features of PAIS, such as hypospadias or gynecomastia. This underlines the importance of including AR gene analysis in the evaluation of isolated micropenis with normal plasma T to ensure proper management of the patient and appropriate genetic counseling for the family. PMID- 20305677 TI - Association between paternal schizophrenia and low birthweight: ADAM12 may matter. PMID- 20305678 TI - Different magnitude of resistance to nondepolarizing muscle relaxants in the denervated mouse skeletal muscle. AB - AIM: To test the hypothesis that different magnitude of resistance of denervated skeletal muscle to nondepolarizing muscle relaxants (NDMRs) is related to their varying potencies at epsilon-AChR and gamma-AChR. METHODS: Both innervated and denervated mouse muscle cells, and human embryonic kidney 293 (HEK293) cells expressing epsilon-AChR or gamma-AChR were used. The effects of NDMRs on nAChR were explored using whole-cell patch clamp technique. RESULTS: NDMRs vecuronium (VEC), atracurium (ATR) and rocuronium (ROC) produced reversible, dose-dependent inhibition on the currents induced by 30 micromol/L acetylcholine both in innervated and denervated skeletal muscle cells. Compared to those obtained in innervated skeletal muscle cells, denervation shifted the concentration-response curves rightward and significantly increased the 50% inhibitory concentration (IC(50)) values (VEC: from 11.2 to 39.2 nmol/L, P<0.01; ATR: from 24.4 to 129.0 nmol/L, P<0.01; ROC: from 37.9 to 101.4 nmol/L, P<0.01). In HEK293 cell expression system, ATR was less potent at gamma-AChR than epsilon-AChR (IC(50) values: 35.9 vs 22.3 nmol/L, P<0.01), VEC was equipotent at both receptor subtypes (IC(50) values: 9.9 vs 10.2 nmol/L, P>0.05), while ROC was more potent at gamma-AChR than epsilon-AChR (IC(50) values: 22.3 vs 33.5 nmol/L, P<0.05). CONCLUSION: Magnitude differences of resistance to different NDMRs caused by denervation are associated with distinct potencies of NDMRs at nAChR subtypes. PMID- 20305679 TI - A variation in NOS1AP gene is associated with repaglinide efficacy on insulin resistance in type 2 diabetes of Chinese. AB - AIM: To investigate a potential association between SNP rs10494366 in the neural nitric oxide synthase adaptor protein (NOS1AP) and efficacy of repaglinide (an insulin secretagogue) in newly diagnosed Shanghai Chinese type 2 diabetes patients. METHODS: A total of 104 newly diagnosed type 2 diabetes patients (69 men, 35 women) were recruited and treated with repaglinide for 24 weeks. Anthropometric measurements, clinical laboratory tests were obtained at baseline and after 24-week treatment. Genotyping was performed by sequencing. RESULTS: The baseline value of BMI, HOMA-IR, HOMA-B, and fasting insulin level were significantly different between GG, GT, and TT genotypes (P=0.024, 0.030, 0.005, and 0.007, respectively). Carriers of TT genotype were in significant insulin resistance at baseline. After 24-week repaglinide monotherapy, the Delta value of fasting insulin (P=0.019) and HOMA-IR (P=0.011) were significantly different. TT carriers had the least insulin resistance after treatment. The mixed model analysis showed that the variation had an interaction effect with repaglinide treatment only on HOMA-IR (P=0.013). CONCLUSION: A common variant in rs10494366 is associated with repaglinide monotherapy efficacy on insulin resistance in newly diagnosed Shanghai Chinese type 2 diabetes patients. PMID- 20305680 TI - Protective effects of prostaglandin E1 on human umbilical vein endothelial cell injury induced by hydrogen peroxide. AB - AIM: To investigate the protective effects of prostaglandin E(1) (PGE(1)) against H(2)O(2)-induced oxidative damage on human umbilical vein endothelial cells (HUVECs). METHODS: HUVECs were pretreated with PGE(1) (0.25, 0.50, and 1.00 micromol/L) for 24 h and exposed to H(2)O(2) (200 micromol/L) for 12 h, and cell viability was measured by the MTT assay. LDH, NO, SOD, GSH-Px, MDA, ROS, and apoptotic percentage were determined. eNOS expression was measured by Western blotting and real-time PCR. RESULTS: PGE(1) (0.25-1.00 micromol/L) was able to markedly restore the viability of HUVECs under oxidative stress, and scavenged intracellular reactive oxygen species induced by H(2)O(2). PGE(1) also suppressed the production of lipid peroxides, such as MDA, restored the activities of endogenous antioxidants including SOD and GSH-Px, and inhibited cell apoptosis. In addition, PGE(1) significantly increased NO content, eNOS protein, and mRNA expression. CONCLUSION: PGE(1) effectively protected endothelial cells against oxidative stress induced by H(2)O(2), an activity that might depend on the up regulation of NO expression. PMID- 20305681 TI - Atorvastatin inhibits homocysteine-induced dysfunction and apoptosis in endothelial progenitor cells. AB - AIM: To investigate the protective effects of atorvastatin on homocysteine (Hcy) induced dysfunction and apoptosis in endothelial progenitor cells (EPCs) and the possible molecular mechanisms. METHODS: EPCs were divided into six groups: Hcy treatment groups (0, 50, and 500 micromol/L) and atorvastatin pretreatment groups (0.1, 1, and 10 micromol/L). EPC proliferation, migration, in vitro vasculogenesis activity, and apoptosis rate were assayed by the MTT assay, modified Boyden chamber assay, in vitro vasculogenesis kit, and AnnexinV-FITC apoptosis detection kit, respectively. The level of reactive oxygen species (ROS) in cells was measured using H(2)DCF-DA as a fluorescence probe. The activity of NADPH oxidase was evaluated with lucigenin-enhanced chemiluminescence. NO in the supernatant was detected by the nitrate reductase assay. The eNOS mRNA expression and p-eNOS, p-Akt, p-p38MAPK protein expression were measured by RT-PCR and Western blotting analysis, respectively. Caspase-3 activity was determined by colorimetric assay. RESULTS: Hcy does-dependently impaired the proliferation, migration and in vitro vasculogenesis capacity of EPCs, induced cell apoptosis, increased ROS accumulation and NADPH oxidase activation, and decreased the secretion of NO compared with the control group (P<0.05 or P<0.01). The detrimental effects of Hcy were attenuated by atorvastatin pretreatment. Furthermore, Hcy caused a significant downregulation of eNOS mRNA, p-eNOS, and p Akt protein expression as well as an upregulation of p-p38MAPK protein expression and caspase-3 activity. These effects of Hcy on EPCs were reversed by atorvastatin in a does-dependent manner. CONCLUSION: Atorvastatin inhibited homocysteine-induced dysfunction and apoptosis in endothelial progenitor cells, which may be related to its effects on suppressing oxidative stress, up regulating Akt/eNOS and down-regulating the p38MAPK/caspase-3 signaling pathway. PMID- 20305682 TI - Transfer and distribution of amoxicillin in the rat gastric mucosa and gastric juice and the effects of rabeprazole. AB - AIM: To investigate the distribution of amoxicillin in the gastric juice and gastric mucosa of rats and to investigate the effects of proton pump inhibitor rabeprazole on amoxicillin concentrations in various compartments. METHODS: One hundred and sixty anesthetized rats were divided into five groups, and given intravenously different doses of amoxicillin or amoxicillin and rabeprazole. The pH value and volume of gastric juice was aspirated were measured and separated gastric mucosa was homogenized. The concentrations of amoxicillin in the plasma, gastric juice and gastric mucosa were measured by high performance liquid chromatography (HPLC). RESULTS: The maximum concentrations of amoxicillin in gastric juice and gastric mucosa were significantly lower than those in plasma (P<0.001). Concentrations in the glandular stomach mucosa were higher than those in the forestomach mucosa. Rabeprazole did not significantly change the pharmacokinetic parameters of amoxicillin in the plasma and did not alter gastric antibiotic clearance or the gastric transfer fraction of amoxicillin in gastric juice. However, rabeprazole did increase the amoxicillin concentration and pH value in gastric juice and reduced the volume of the gastric juice. CONCLUSION: Amoxicillin could penetrate the gastric mucosa and achieve therapeutic concentrations at the target site after transfer from the blood to the stomach. Rabeprazole increased the amoxicillin concentration in gastric juice by decreasing the gastric juice volume but did not affect its concentration in blood or gastric mucosa. PMID- 20305683 TI - Association analysis of genetic polymorphisms and potential interaction of the osteocalcin (BGP) and ER-alpha genes with body mass index (BMI) in premenopausal Chinese women. AB - AIM: To investigate whether estrogen receptor alpha (ER-alpha) PvuII and osteocalcin (also known as bone Gla protein, or BGP) HindIII genetic polymorphisms and their potential interactions are associated with body mass index (BMI) variation. METHODS: Data on BMI and ER-alpha PvuII and BGP HindIII genotypes were obtained from 328 healthy premenopausal Chinese women in east China. The study subjects were unrelated, at least 21 years old (mean age of 33.2+/-5.9 years), and had an average BMI of 21.58+/-2.59. All subjects were genotyped at the ER-alpha PvuII and BGP HindIII loci using polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP). RESULTS: The BGP HindIII genotypes were significantly associated with BMI (P=0.003). Carriers of the HH and Hh genotypes had approximately 2.73% and 1.27% higher BMI than those of the hh genotype, respectively. In contrast, the ER-alpha PvuII polymorphism was not significantly associated with BMI (P=0.454). In addition, there was no evidence of potential interactions between the ER-alpha and BGP genes in our subjects (P>or=0.013). CONCLUSION: The HindIII polymorphism of the BGP gene, but not the PvuII polymorphism of the ER-alpha gene or their potential interaction, was associated with BMI in premenopausal Chinese women. PMID- 20305684 TI - Curcumin reverses T cell-mediated adaptive immune dysfunctions in tumor-bearing hosts. AB - Immune dysfunction is well documented during tumor progression and likely contributes to tumor immune evasion. CD8(+) cytotoxic T lymphocytes (CTLs) are involved in antigen-specific tumor destruction and CD4(+) T cells are essential for helping this CD8(+) T cell-dependent tumor eradication. Tumors often target and inhibit T-cell function to escape from immune surveillance. This dysfunction includes loss of effector and memory T cells, bias towards type 2 cytokines and expansion of T regulatory (Treg) cells. Curcumin has previously been shown to have antitumor activity and some research has addressed the immunoprotective potential of this plant-derived polyphenol in tumor-bearing hosts. Here we examined the role of curcumin in the prevention of tumor-induced dysfunction of T cell-based immune responses. We observed severe loss of both effector and memory T-cell populations, downregulation of type 1 and upregulation of type 2 immune responses and decreased proliferation of effector T cells in the presence of tumors. Curcumin, in turn, prevented this loss of T cells, expanded central memory T cell (T(CM))/effector memory T cell (T(EM)) populations, reversed the type 2 immune bias and attenuated the tumor-induced inhibition of T-cell proliferation in tumor-bearing hosts. Further investigation revealed that tumor burden upregulated Treg cell populations and stimulated the production of the immunosuppressive cytokines transforming growth factor (TGF)-beta and IL-10 in these cells. Curcumin, however, inhibited the suppressive activity of Treg cells by downregulating the production of TGF-beta and IL-10 in these cells. More importantly, curcumin treatment enhanced the ability of effector T cells to kill cancer cells. Overall, our observations suggest that the unique properties of curcumin may be exploited for successful attenuation of tumor-induced suppression of cell-mediated immune responses. PMID- 20305685 TI - The enigmatic processing and secretion of interleukin-33. AB - Interleukin-33 (IL-33) is the most attractive novel cytokine identified as an IL 1 family member. IL-33 was first named NF-HEV (nuclear factor from high endothelial venules), as it was known to interact with nuclear chromatin although its exact intracellular functions are still to be clarified. IL-33 is now recognized as the specific ligand for the orphan IL-1 receptor family member ST2 and to be involved in polarization of T cells towards T helper 2 cell phenotype and in activation of mast cells, bosophils, eosinophils and natural killer cells. It is essential for IL-33 to be extracellularly released in order to bind to the ST2 receptor and consequently play a crucial role in inflammatory, infectious and autoimmune diseases. However, like the IL-1 family members, IL-1beta and IL-18, IL-33 mRNA is translated without a signal sequence for secretion. Additionally, IL-33 cannot be released by the processing and secretion mechanism shared by IL 1beta and IL-18 as IL-33 is not a substrate of caspase-1 and does not require proteolysis for activation. In contrast, IL-33 can be inactivated by apoptotic caspases. Accordingly, IL-33 is proposed to be released as an alarmin from necrotic cells but to be deleted during apoptosis. Besides the known autocrine, paracrine, intracrine, juxtacrine and retrocrine mechanisms of cellular interaction with cytokines, release by necrotic cells is another pathway for a cytokine to display its function, which we suggest might be called 'necrocrine'. This mini review summarizes recent progress of how IL-33 displays potential immunoregulatory roles with a particular focus on its enigmatic production. PMID- 20305686 TI - Th17 cells and their associated cytokines in liver diseases. AB - T helper 17 (Th17) cells are a newly identified subset of T helper cells that play important roles in host defense against extracellular bacteria as well as in the pathogenesis of autoimmune disease. The functions of Th17 cells are mediated via the production of several cytokines including interleukin (IL)-17 and IL-22. Recent studies show that the frequency of IL-17(+) cells is significantly elevated in a variety of chronic liver diseases including alcoholic liver disease, viral hepatitis and hepatocellular carcinoma. IL-17 receptor is expressed virtually on all types of liver cells, while IL-22 receptor expression is restricted to epithelial cells including hepatocytes in the liver. IL-17 seems to play an important role in inducing liver inflammation via stimulating multiple types of liver nonparenchymal cells to produce proinflammatory cytokines and chemokines, while IL-22 appears to be an important factor in promoting hepatocyte survival and proliferation. PMID- 20305688 TI - Integrin-linked kinase has a critical role in ErbB2 mammary tumor progression: implications for human breast cancer. AB - Elevated expression of the integrin-linked kinase (ILK) has been observed in a variety of cancers and has been further correlated with poor clinical outcome. Here, we show that mammary epithelial disruption of ILK results in a profound block in mammary tumor induction. Consistent with these observations, inhibition of ILK function in ErbB2-expressing cells with small molecule inhibitor or RNA interference resulted in profound block in their in vitro invasive properties due to the induction of apoptotic cell death. The rare ILK-deficient tumors that eventually arose overcame this block in tumor induction by an upregulation of ErB3 phosphorylation. These observations provide direct evidence that ILK has a critical role in the initiation phase of ErbB2 tumor induction. PMID- 20305689 TI - A deficiency in Mdm2 binding protein inhibits Myc-induced B-cell proliferation and lymphomagenesis. AB - Mdm2 binding protein (MTBP) has been implicated in cell-cycle arrest and the Mdm2/p53 tumor suppressor pathway through its interaction with Mdm2. To determine the function of MTBP in tumorigenesis and its potential role in the Mdm2/p53 pathway, we crossed Mtbp-deficient mice to Emu-myc transgenic mice, in which overexpression of the oncogene c-Myc induces B-cell lymphomas primarily through inactivation of the Mdm2/p53 pathway. We report that Myc-induced B-cell lymphoma development in Mtbp heterozygous mice was profoundly delayed. Surprisingly, reduced levels of Mtbp did not lead to an increase in B-cell apoptosis or affect Mdm2. Instead, an Mtbp deficiency inhibited Myc-induced proliferation and the upregulation of Myc target genes necessary for cell growth. Consistent with a role in proliferation, Mtbp expression was induced by Myc and other factors that promote cell-cycle progression and was elevated in lymphomas from humans and mice. Therefore, Mtbp functioned independent of Mdm2 and was a limiting factor for the proliferative and transforming functions of Myc. Thus, Mtbp is a previously unrecognized regulator of Myc-induced tumorigenesis. PMID- 20305690 TI - Overexpression of transcriptional coactivator AIB1 promotes hepatocellular carcinoma progression by enhancing cell proliferation and invasiveness. AB - Amplified in breast cancer 1 (AIB1) is a transcriptional coactivator for nuclear receptors and other transcription factors. AIB1 has an important role in malignancy of several cancers such as breast and prostate cancers. However, its involvement in human hepatocellular carcinoma (HCC) progression remains unclear. Here, we found that AIB1 protein was overexpressed in 23 of 34 human HCC specimens (68%). Down-regulation of AIB1 reduced HCC cell proliferation, migration, invasion, colony formation ability and tumorigenic potential in nude mice. These phenotypic changes caused by AIB1 knockdown correlated with increased expression of the cell cycle inhibitor p21(Cip1/Waf1) and decreased Akt activation and the expression of proliferating cell nuclear antigen (PCNA) and matrix metallopeptidase MMP-9. In agreement with these findings, clinical AIB1 positive HCC expressed higher levels of PCNA than AIB1-negative HCC. A positive correlation was established between the levels of AIB1 protein and PCNA protein in HCC, suggesting that AIB1 may contribute to HCC cell proliferation. In addition, MMP-9 expression in AIB1-postive HCC was significantly higher than that in AIB1-negative HCC, suggesting that AIB1-postive HCC may be more invasive. Collectively, our results show that overexpression of AIB1 promotes human HCC progression by enhancing cell proliferation and invasiveness. Therefore, AIB1 is a master regulator of human HCC growth and might be a useful molecular target for HCC prognosis and treatment. PMID- 20305691 TI - De-repression of CTGF via the miR-17-92 cluster upon differentiation of human glioblastoma spheroid cultures. AB - All-trans retinoic acid is a potent promoter of cellular differentiation processes, which is used in cancer therapy. Glioblastoma spheroid cultures are enriched in tumor-initiating cells, and provide a model to test new treatment options in vitro. We investigated the molecular mechanisms of response to exposure to differentiation-promoting conditions in such cultures. Microarray analyses of five independent cultures showed that after induction of differentiation, inhibitors of transforming growth factor-beta/bone morphogenetic protein, Wnt/beta-catenin and IGF signaling were upregulated, whereas expression of several microRNAs decreased, particularly that of the miR-17-92 cluster. In primary astrocytic gliomas (n=82), expression of several members of miR-17-92 was significantly higher relative to those of normal brain (n=8) and significantly increased with tumor grade progression (P<0.05). A high-level amplification of the miR-17-92 locus was detected in one glioblastoma specimen. Transfection of inhibitors of miR-17-92 induced increased apoptosis and decreased cell proliferation in glioblastoma spheroids. Mir-17-92 inhibition was also associated with increased messenger RNA (mRNA) and/or protein expression of CDKN1A, E2F1, PTEN and CTGF. The CTGF gene was shown to be a target of miR-17-92 in glioblastoma spheroids by luciferase reporter assays. Our results suggest that miR-17-92 and its target CTGF mediate effects of differentiation-promoting treatment on glioblastoma cells through multiple regulatory pathways. PMID- 20305692 TI - Bortezomib decreases Rb phosphorylation and induces caspase-dependent apoptosis in Imatinib-sensitive and -resistant Bcr-Abl1-expressing cells. AB - The use of c-abl-specific inhibitors such as Imatinib (IM) or Dasatinib has revolutionized the treatment of chronic myeloid leukemia (CML). However, a significant percentage of patients become resistant to IM. In this report, we have analyzed the possibility of using the proteasome as a molecular target in CML. Our results show that cells that express Bcr-Abl1 are more sensitive to the inhibition of the proteasome with Bortezomib (Btz) than control cells. This treatment reduces the proliferation of Bcr-Abl1-expressing cells, by inactivating NF-kappaB2 and decreasing the phosphorylation of Rb, eventually leading to an increase in caspase-dependent apoptosis. Furthermore, we show that Btz also induces cell-cycle arrest and apoptosis in cells expressing Bcr-Abl1 mutants that are resistant to IM. These results unravel a new molecular target of Btz, that is the Rb pathway, and open new possibilities in the treatment of CML especially for patients that become resistant to IM because of the presence of the T315I mutation. PMID- 20305693 TI - Meta-analysis of adrenocortical tumour genomics data: novel pathogenic pathways revealed. AB - Sporadic adrenocortical tumours are common, but their pathogenesis is poorly elucidated. In this study, we present a meta-analysis and review of gene expression microarray and comparative genome hybridization (CGH) studies performed to date on these tumours, including our own data. Data of whole genome microarray studies from altogether 164 tumours (97 benign, 67 malignant) and 18 normal tissues were reclassified and reanalysed. Significant gene sets and cytogenetic changes from publications without available genomic data were also examined including 269 benign, 215 malignant tumour and 30 normal tissues. In our experimental study, 11 tumour and four normal samples were analysed by parallel mRNA and CGH profiling. Data were examined by an integrative bioinformatics approach (GeneSpring, Gene Set Enrichment Analysis and Ingenuity Pathway Analysis softwares) searching for common gene expression changes and paralleling chromosome aberrations. Both meta-analysis of available mRNA and CGH profiling data and our experimental study revealed three major pathogenetic pathways: (1) cell cycle, (2) retinoic acid signalling (including lipopolysaccharide/Toll like receptor 4 pathway), (3) complement system and antigen presentation. These pathways include novel, previously undescribed pathomechanisms of adrenocortical tumours, and associated gene products may serve as diagnostic markers of malignancy and therapeutic targets. PMID- 20305694 TI - Artemin is estrogen regulated and mediates antiestrogen resistance in mammary carcinoma. AB - We have previously identified an oncogenic role of artemin (ARTN), a member of glial cell derived neurotrophic factor family of ligands, in mammary carcinoma. We herein report that ARTN is an estrogen-inducible gene. Meta-analysis of gene expression data sets showed that ARTN expression is positively correlated to estrogen receptor (ER) status in human mammary carcinoma. Furthermore, in patients with ER-positive mammary carcinoma treated with tamoxifen, high ARTN expression is significantly correlated with decreased survival. Forced expression of ARTN in ER-positive human mammary carcinoma cells increased ER transcriptional activity, promoted estrogen-independent growth and produced resistance to tamoxifen and fulvestrant in vitro and to tamoxifen in xenograft models. ARTN stimulated resistance to tamoxifen and fulvestrant is mediated by increased BCL-2 expression. Conversely, depletion of endogenous ARTN by small-interfering RNA or functional antagonism of ARTN by antibody enhanced the efficacy of antiestrogens. Tamoxifen decreased ARTN expression in tamoxifen-sensitive mammary carcinoma cells whereas ARTN expression was increased in tamoxifen-resistant cells and not affected by tamoxifen treatment. Antibody inhibition of ARTN in tamoxifen resistant cells improved tamoxifen sensitivity. Functional antagonism of ARTN therefore warrants consideration as an adjuvant therapy to enhance antiestrogen efficacy in ER-positive mammary carcinoma. PMID- 20305695 TI - Human stem cells expressing novel TSP-1 variant have anti-angiogenic effect on brain tumors. AB - Novel therapeutic agents combined with innovative modes of delivery and non invasive imaging of drug delivery, pharmacokinetics and efficacy are crucial in developing effective clinical anticancer therapies. In this study, we have created and characterized multiple novel variants of anti-angiogenic protein thrombospondin (aaTSP-1) that comprises unique regions of three type-I-repeats of TSP-1 and used engineered human neural stem cells (hNSC) to provide sustained on site delivery of secretable aaTSP-1 to tumor-vasculature. We show that hNSC-aaTSP 1 has anti-angiogenic effect on human brain and dermal microvascular endothelial cells co-cultured with established glioma cells and CD133+ glioma-initiating cells. Using human glioma cells and hNSC engineered with different combinations of fluorescent and bioluminescent marker proteins and employing multi-modality imaging techniques, we show that aaTSP-1 targets the vascular-component of gliomas and a single administration of hNSC-aaTSP-1 markedly reduces tumor vessel density that results in inhibition of tumor-progression and increased survival in mice bearing highly malignant human gliomas. We also show that therapeutic hNSC do not proliferate and remain in an un-differentiated state in the brains of glioma-bearing mice. This study provides a platform for accelerated development of future cell-based therapies for cancer. PMID- 20305696 TI - Ganglioside synthase knockout in oncogene-transformed fibroblasts depletes gangliosides and impairs tumor growth. AB - Biologically active membrane gangliosides, expressed and released by many human tumors, are hypothesized to significantly impact tumor progression. Lack of a model of complete and specific tumor ganglioside depletion in vivo, however, has hampered elucidation of their role. Here, we report the creation of a novel, stable, genetically induced tumor cell system resulting in specific and complete blockade of ganglioside synthesis. Wild-type (WT) and GM3 synthase/GM2 synthase double knockout (DKO) murine embryonic fibroblasts were transformed using amphotropic retrovirus-transduced oncogenes (pBABE-c-Myc(T58A)+H-RasG12V). The transformed cells, WT(t) and DKO(t) respectively, evidenced comparable integrated copy numbers and oncogene expression. Ganglioside synthesis was completely blocked in the DKO(t) cells, importantly without triggering an alternate pathway of ganglioside synthesis. Ganglioside depletion (to <0.5 nmol/10(7) cells from 9 to 11 nmol/10(7) WT(t) or untransfected normal fibroblasts) did not adversely affect cell proliferation kinetics but did reduce cell migration on fibronectin coated wells, consistent with our previous observations in ganglioside-depleted normal human fibroblasts. Strikingly, despite similar oncogene expression and growth kinetics, DKO(t) cells evidenced significantly impaired tumor growth in syngeneic immunocompetent mice, underscoring the pivotal role of tumor cell gangliosides and providing an ideal system for probing their mechanisms of action in vivo. PMID- 20305697 TI - Role of CK1 in GSK3beta-mediated phosphorylation and degradation of snail. AB - The epithelial to mesenchymal transition (EMT) that occurs during embryonic development has begun to attract attention as a potential mechanism for tumor cell metastasis. Snail is a well-known Zn-finger transcription factor that promotes EMT by repressing E-cadherin expression. It is known that Snail is phosphorylated by GSK3beta and degraded by beta-TrCP-mediated ubiquitination. Here we described another protein kinase, CK1, whose phosphorylation of Snail is required for the subsequent GSK3beta phosphorylation. Specific inhibition or depletion of CK1varepsilon inhibits the phosphorylation and degradation of Snail and promotes cell migration, suggesting a central role of CK1varepsilon in the EMT process. Furthermore, our study uncovered distinct roles and steps of Snail phosphorylation by CK1varepsilon and GSK3beta. Taken together, we identified CK1varepsilon as a new component of the Snail-mediated EMT process, providing insight into the mechanism of human cancer metastasis. PMID- 20305698 TI - Safety and efficacy of targeted busulfan therapy in children undergoing myeloablative matched sibling donor BMT for sickle cell disease. AB - Busulfan influences engraftment and toxicities during hematopoietic stem cell transplantation (HSCT). We report our single-institution experience of targeted busulfan therapy for myeloablative, matched sibling donor (MSD) HSCT for sickle cell disease (SCD) and assess the relationships of busulfan levels to engraftment and toxicities. Twenty-seven patients with SCD underwent MSD HSCT from 1993 to 2007, 25 with busulfan measurements. The conditioning regimen was busulfan (initial dose 0.875 mg/kg for 16 doses), CY and antithymocyte globulin. Busulfan area under curve (AUC) was determined with the first dose, and dose adjustments were made to target the desired AUC range. Median AUC was 963 MUmol min/L (range 780-1305 MUmol min/L). Engraftment occurred in all cases: 21 (84%) full donor chimerism (> 95% donor cells), 4 (16%) partial donor chimerism. Hepatic veno occlusive disease (VOD) occurred in 8 (32%) patients. Lower AUC was seen with partial donor chimerism (862 +/- 73 MUmol min/L) versus full donor chimerism (AUC 1018 +/- 122 MUmol min/L) (P = 0.022). VOD was not associated with busulfan AUC (P = 0.153). Of 25 patients, 24 survived with median follow-up of 4.9 years. Our experience shows that targeting busulfan AUC above the range used in previous multicenter trials appears safe and may contribute to sustained engraftment in SCD. PMID- 20305699 TI - Comparison of donor chimerism following myeloablative and nonmyeloablative allogeneic hematopoietic SCT. AB - Surveillance of hematopoietic chimerism following hematopoietic SCT (HSCT) with nonmyeloablative (NMA) preparative regimens is standard to assess the need for clinical intervention. Monitoring of donor chimerism following HSCT with myeloablative (MA) preparative regimens is, however, not considered useful because engraftment is thought to occur rapidly and consistently. This study compares the timing of donor hematopoietic cell engraftment in patients undergoing NMA conditioning with fludarabine and TBI with those receiving MA conditioning with BU- or TBI-based regimens. Achievement of >= 90% donor leukocyte chimerism occurred rapidly and consistently in all three groups and time to achievement of >= 90% donor T cells was similar among the three groups (P = 0.57). Achievement of >= 90% donor leukocyte chimerism was not associated with risk of acute or chronic GVHD, graft rejection, relapse or all cause mortality in multivariate analyses. Donor T-cell chimerism of >= 90% was significantly associated with development of extensive chronic GVHD. The value of routine surveillance of chimerism following any of the preparative regimens used in this study should be reevaluated. PMID- 20305700 TI - Plerixafor plus granulocyte CSF can mobilize hematopoietic stem cells from multiple myeloma and lymphoma patients failing previous mobilization attempts: EU compassionate use data. AB - Plerixafor was recently approved by the US Food and Drug Administration (FDA) and the European Medicines Evaluation Agency (EMEA) to enhance stem cell mobilization for autologous transplant in patients with lymphoma and multiple myeloma. In this study, we present the first European compassionate use experience in mobilization failures, patients who are hardest to remobilize but were not included in registration trials. A total of 56 consecutive patients from 15 centers in Spain and the United Kingdom were included: age 60 (33-69) years; 29 men (32 with myeloma and 24 with lymphoma); 2 lines of previous chemotherapy (1-10); 73 previously failed mobilization attempts with G-CSF (28), chemotherapy plus G-CSF (43) or G-CSF plus SCF(2). Overall, 71% of patients reached >= 10 CD34+ cells per MUL with plerixafor on day 5 after a 7.6-fold expansion from day 4. A total of 42 patients (75%) collected >= 2 * 106, average 3.0 +/- 1.7 (0.4-10.6) CD34+ cells per kg with plerixafor plus G-CSF. There were no severe drug-related adverse events. In all, 35 patients (63%) underwent transplant, receiving an average of 3.1+/-1.2 (1.9-7.7) * 106 CD34+ cells per kg. All patients engrafted neutrophils (day 12; 13.4 +/- 0.8; 8-30) and platelets (day 15; 18.5 +/- 2.4; 8-33). In our experience, plerixafor offers an effective alternative to collect sufficient CD34+ cells for autologous SCT from patients who fail conventional mobilization methods, with good tolerance and a high success rate. PMID- 20305701 TI - Bortezomib and donor lymphocyte infusion in multiple myeloma relapsed after allo SCT does not result in durable remissions. PMID- 20305702 TI - Going straight to the point: intra-BM injection of hematopoietic progenitors. AB - Intra-BM injection (IBMI) has been used clinically as a technique to deliver medications, blood products and fluids to critically ill children and war-wounded soldiers. Interest in IBMI has now been renewed in the setting of hematopoietic cell transplantation, in particular when umbilical cord blood is the graft source. Clinical studies have not yet unequivocally shown improvement in hematopoietic recovery. However, most intriguing is the observation, both in the clinical setting and in murine models, that the IBMI delivery of hematopoietic grafts and lymphocytes may reduce in the risk of acute GVHD. The underlying mechanism of the reduced risk of GVHD requires further investigation. In this study, we review the rationale as well as the clinical and pre-clinical data that support the study of IBMI as a method to deliver hematopoietic cells. PMID- 20305703 TI - Plastic parasites: sophisticated strategies for survival and reproduction? AB - Adaptive phenotypic plasticity in life history traits, behaviours, and strategies is ubiquitous in biological systems. It is driven by variation in selection pressures across environmental gradients and operates under constraints imposed by trade-offs. Phenotypic plasticity has been thoroughly documented for multicellular taxa, such as insects, birds and mammals, and in many cases the underlying selective pressures are well understood. Whilst unicellular parasites face many of the same selective pressures and trade-offs, plasticity in their phenotypic traits has been largely overlooked and remains poorly understood. Here, we demonstrate that evolutionary theory, developed to explain variation observed in the life-history traits of multicellular organisms, can be applied to parasites. Though our message is general - we can expect the life-histories of all parasites to have evolved phenotypic plasticity - we focus our discussion on malaria parasites. We use an evolutionary framework to explain the trade-offs that parasites face and how plasticity in their life history traits will be expressed according to changes in their in-host environment. Testing whether variation in parasites traits is adaptive will provide new and fundamental insights into the basic biology of parasites, their epidemiology and the processes of disease during individual infections. PMID- 20305704 TI - Lack of fit in self modeling regression: application to pulse waveforms. AB - Self modeling regression (SEMOR) is an approach for modeling sets of observed curves that have a common shape (or sequence of features) but have variability in the amplitude (y-axis) and/or timing (x-axis) of the features across curves. SEMOR assumes the x and y axes for each observed curve can be separately transformed in a parametric manner so that the features across curves are aligned with the common shape, usually represented by non-parametric function. We show that when the common shape is modeled with a regression spline and the transformational parameters are modeled as random with the traditional distribution (normal with mean zero), the SEMOR model may surprisingly suffer from lack of fit and the variance components may be over-estimated. A random effects distribution that restricts the predicted random transformational parameters to have mean zero or the inclusion of a fixed transformational parameter improves estimation. Our work is motivated by arterial pulse pressure waveform data where one of the variance components is a novel measure of short term variability in blood pressure. PMID- 20305705 TI - Non-Markov multistate modeling using time-varying covariates, with application to progression of liver fibrosis due to hepatitis C following liver transplant. AB - Multistate modeling methods are well-suited for analysis of some chronic diseases that move through distinct stages. The memoryless or Markov assumptions typically made, however, may be suspect for some diseases, such as hepatitis C, where there is interest in whether prognosis depends on history. This paper describes methods for multistate modeling where transition risk can depend on any property of past progression history, including time spent in the current stage and the time taken to reach the current stage. Analysis of 901 measurements of fibrosis in 401 patients following liver transplantation found decreasing risk of progression as time in the current stage increased, even when controlled for several fixed covariates. Longer time to reach the current stage did not appear associated with lower progression risk. Analysis of simulation scenarios based on the transplant study showed that greater misclassification of fibrosis produced more technical difficulties in fitting the models and poorer estimation of covariate effects than did less misclassification or error-free fibrosis measurement. The higher risk of progression when less time has been spent in the current stage could be due to varying disease activity over time, with recent progression indicating an "active" period and consequent higher risk of further progression. PMID- 20305706 TI - An introduction to causal inference. AB - This paper summarizes recent advances in causal inference and underscores the paradigmatic shifts that must be undertaken in moving from traditional statistical analysis to causal analysis of multivariate data. Special emphasis is placed on the assumptions that underlie all causal inferences, the languages used in formulating those assumptions, the conditional nature of all causal and counterfactual claims, and the methods that have been developed for the assessment of such claims. These advances are illustrated using a general theory of causation based on the Structural Causal Model (SCM) described in Pearl (2000a), which subsumes and unifies other approaches to causation, and provides a coherent mathematical foundation for the analysis of causes and counterfactuals. In particular, the paper surveys the development of mathematical tools for inferring (from a combination of data and assumptions) answers to three types of causal queries: those about (1) the effects of potential interventions, (2) probabilities of counterfactuals, and (3) direct and indirect effects (also known as "mediation"). Finally, the paper defines the formal and conceptual relationships between the structural and potential-outcome frameworks and presents tools for a symbiotic analysis that uses the strong features of both. The tools are demonstrated in the analyses of mediation, causes of effects, and probabilities of causation. PMID- 20305707 TI - Attributable fractions for sufficient cause interactions. AB - A number of results concerning attributable fractions for sufficient cause interactions are given. Results are given both for etiologic fractions (i.e. the proportion of the disease due to a particular sufficient cause) and for excess fractions (i.e. the proportion of disease that could be eliminated by removing a particular sufficient cause). Results are given both with and without assumptions of monotonicity. Under monotonicity assumptions, exact formulas can be given for the excess fraction. When etiologic fractions are of interest or when monotonicity assumptions do not hold for excess fractions then only lower bounds can be given. The interpretation of the results in this paper and in a proposal by Hoffmann et al. (2006) are discussed and compared. A method is described to estimate the lower bounds on attributable fractions using marginal structural models. Identification is discussed in settings in which time-dependent confounding may be present. PMID- 20305708 TI - Immediate reconstruction of complex hand trauma with iliac crest bone graft and 2 pedicled fasciocutaneous skin flaps: a case report. AB - OBJECTIVE: The decision about primary or staged reconstruction of all structures in severe hand injuries is controversial. The purpose of this case report is to present a surgical protocol that lead to good functional results and rapid recovery after primary bone grafting with pedicled flap coverage of a complex hand injury. METHODS: A case is reported in which 2 iliac crest bone grafts, an extended dorsal metacarpal artery flap and a heterodigital island flap, were performed at primary intervention to reconstruct the index and middle fingers of a 17-year-old patient. RESULTS: Length and sensation of the digits were fully preserved while the destroyed joints were fused and covered with mobile soft tissue. Hereby, a satisfactory pinch grip and hand closure was restored, allowing the patient to return to work after only 2 months. CONCLUSIONS: Given proper planning and adequate debridement, primary reconstruction of all injured structures should be considered when dealing with complex hand injuries. PMID- 20305709 TI - Transplant course: the art of liver transplantation. PMID- 20305710 TI - Adenosine and epilepsy-thinking beyond A(1) receptors. PMID- 20305711 TI - Cytotoxic effects of G(M1) ganglioside and amyloid beta-peptide on mouse embryonic neural stem cells. AB - AD (Alzheimer's disease) is a neurodegenerative disease and the most common form of dementia. One of the pathological hallmarks of AD is the aggregation of extracellular Abetas (amyloid beta-peptides) in senile plaques in the brain. The process could be initiated by seeding provided by an interaction between G(M1) ganglioside and Abetas. Several reports have documented the bifunctional roles of Abetas in NSCs (neural stem cells), but the precise effects of G(M1) and Abeta on NSCs have not yet been clarified. We evaluated the effect of G(M1) and Abeta-(1 40) on mouse NECs (neuroepithelial cells), which are known to be rich in NSCs. No change of cell number was detected in NECs cultured in the presence of either G(M1) or Abeta-(1-40). On the contrary, a decreased number of NECs were cultured in the presence of a combination of G(M1) and Abeta-(1-40). The exogenously added G(M1) and Abeta-(1-40) were confirmed to incorporate into NECs. The Ras-MAPK (mitogen-activated protein kinase) pathway, important for cell proliferation, was intact in NECs simultaneously treated with G(M1) and Abeta-(1-40), but caspase 3 was activated. NECs treated with G(M1) and Abeta-(1-40) were positive in the TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling) assay, an indicator of cell death. It was found that G(M1) and Abeta-(1-40) interacted in the presence of cholesterol and sphingomyelin, components of cell surface microdomains. The cytotoxic effect was found also in NSCs prepared via neurospheres. These results indicate that Abeta-(1-40) and G(M1) co-operatively exert a cytotoxic effect on NSCs, likely via incorporation into NEC membranes, where they form a complex for the activation of cell death signalling. PMID- 20305712 TI - Indigenous lands, protected areas, and slowing climate change. AB - Recent climate talks in Copenhagen reaffirmed the crucial role of reducing emissions from deforestation and degradation (REDD). Creating and strengthening indigenous lands and other protected areas represents an effective, practical, and immediate REDD strategy that addresses both biodiversity and climate crises at once. PMID- 20305713 TI - Synopsis. Location matters: how spatial positioning of regulatory proteins produces divergent outcomes. PMID- 20305714 TI - Accelerating policy decisions to adopt haemophilus influenzae type B vaccine: a global, multivariable analysis. AB - BACKGROUND: Adoption of new and underutilized vaccines by national immunization programs is an essential step towards reducing child mortality. Policy decisions to adopt new vaccines in high mortality countries often lag behind decisions in high-income countries. Using the case of Haemophilus influenzae type b (Hib) vaccine, this paper endeavors to explain these delays through the analysis of country-level economic, epidemiological, programmatic and policy-related factors, as well as the role of the Global Alliance for Vaccines and Immunisation (GAVI Alliance). METHODS AND FINDINGS: Data for 147 countries from 1990 to 2007 were analyzed in accelerated failure time models to identify factors that are associated with the time to decision to adopt Hib vaccine. In multivariable models that control for Gross National Income, region, and burden of Hib disease, the receipt of GAVI support speeded the time to decision by a factor of 0.37 (95% CI 0.18-0.76), or 63%. The presence of two or more neighboring country adopters accelerated decisions to adopt by a factor of 0.50 (95% CI 0.33-0.75). For each 1% increase in vaccine price, decisions to adopt are delayed by a factor of 1.02 (95% CI 1.00-1.04). Global recommendations and local studies were not associated with time to decision. CONCLUSIONS: This study substantiates previous findings related to vaccine price and presents new evidence to suggest that GAVI eligibility is associated with accelerated decisions to adopt Hib vaccine. The influence of neighboring country decisions was also highly significant, suggesting that approaches to support the adoption of new vaccines should consider supply- and demand-side factors. PMID- 20305715 TI - Chronic obstructive pulmonary disease: effects beyond the lungs. PMID- 20305716 TI - Sequestration of the Abeta peptide prevents toxicity and promotes degradation in vivo. AB - Protein aggregation, arising from the failure of the cell to regulate the synthesis or degradation of aggregation-prone proteins, underlies many neurodegenerative disorders. However, the balance between the synthesis, clearance, and assembly of misfolded proteins into neurotoxic aggregates remains poorly understood. Here we study the effects of modulating this balance for the amyloid-beta (Abeta) peptide by using a small engineered binding protein (Z(Abeta3)) that binds with nanomolar affinity to Abeta, completely sequestering the aggregation-prone regions of the peptide and preventing its aggregation. Co expression of Z(Abeta3) in the brains of Drosophila melanogaster expressing either Abeta(42) or the aggressive familial associated E22G variant of Abeta(42) abolishes their neurotoxic effects. Biochemical analysis indicates that monomer Abeta binding results in degradation of the peptide in vivo. Complementary biophysical studies emphasize the dynamic nature of Abeta aggregation and reveal that Z(Abeta3) not only inhibits the initial association of Abeta monomers into oligomers or fibrils, but also dissociates pre-formed oligomeric aggregates and, although very slowly, amyloid fibrils. Toxic effects of peptide aggregation in vivo can therefore be eliminated by sequestration of hydrophobic regions in monomeric peptides, even when these are extremely aggregation prone. Our studies also underline how a combination of in vivo and in vitro experiments provide mechanistic insight with regard to the relationship between protein aggregation and clearance and show that engineered binding proteins may provide powerful tools with which to address the physiological and pathological consequences of protein aggregation. PMID- 20305717 TI - Spatial epigenetic control of mono- and bistable gene expression. AB - Bistability in signaling networks is frequently employed to promote stochastic switch-like transitions between cellular differentiation states. Differentiation can also be triggered by antagonism of activators and repressors mediated by epigenetic processes that constitute regulatory circuits anchored to the chromosome. Their regulatory logic has remained unclear. A reaction-diffusion model reveals that the same reaction mechanism can support both graded monostable and switch-like bistable gene expression, depending on whether recruited repressor proteins generate a single silencing gradient or two interacting gradients that flank a gene. Our experiments confirm that chromosomal recruitment of activator and repressor proteins permits a plastic form of control; the stability of gene expression is determined by the spatial distribution of silencing nucleation sites along the chromosome. The unveiled regulatory principles will help to understand the mechanisms of variegated gene expression, to design synthetic genetic networks that combine transcriptional regulatory motifs with chromatin-based epigenetic effects, and to control cellular differentiation. PMID- 20305718 TI - Synopsis. Memory is enhanced at behaviorally relevant times. PMID- 20305719 TI - The sexually antagonistic genes of Drosophila melanogaster. AB - When selective pressures differ between males and females, the genes experiencing these conflicting evolutionary forces are said to be sexually antagonistic. Although the phenotypic effect of these genes has been documented in both wild and laboratory populations, their identity, number, and location remains unknown. Here, by combining data on sex-specific fitness and genome-wide transcript abundance in a quantitative genetic framework, we identified a group of candidate genes experiencing sexually antagonistic selection in the adult, which correspond to 8% of Drosophila melanogaster genes. As predicted, the X chromosome is enriched for these genes, but surprisingly they represent only a small proportion of the total number of sex-biased transcripts, indicating that the latter is a poor predictor of sexual antagonism. Furthermore, the majority of genes whose expression profiles showed a significant relationship with either male or female adult fitness are also sexually antagonistic. These results provide a first insight into the genetic basis of intralocus sexual conflict and indicate that genetic variation for fitness is dominated and maintained by sexual antagonism, potentially neutralizing any indirect genetic benefits of sexual selection. PMID- 20305720 TI - Synopsis. Identifying genes that help one sex but harm the other. PMID- 20305721 TI - Enhanced memory for scenes presented at behaviorally relevant points in time. AB - The ability to remember a briefly presented scene depends on a number of factors, such as its saliency, novelty, degree of threat, or behavioral relevance to a task. Here, however, we show that the encoding of a scene into memory may depend not only on what the scene contains but also when it occurs. Participants performed an attentionally demanding target detection task at fixation while also viewing a rapid sequence of full-field photographs of urban and natural scenes. Participants were then tested on whether they recognized a specific scene from the previous sequence. We found that scenes were recognized reliably only when presented concurrently with a target at fixation. This is evidence of a mechanism where traces of a visual scene are automatically encoded into memory at behaviorally relevant points in time regardless of the spatial focus of attention. PMID- 20305722 TI - Enantioselective syntheses of candenatenins B and C using a chiral anthracene auxiliary. AB - An asymmetric synthesis of two anticancer natural products, candenatenins B and C, is described, leading to a revision of the originally assigned stereochemistry. The synthesis follows a Diels-Alder/retro-Diels Alder strategy using a chiral anthracene auxiliary to access both targets with 90% ee. The inherent structural qualities of the auxiliary allow for both regio- and diastereoselective transformations. PMID- 20305723 TI - Synthesis and In Vitro Evaluation of Taxol oxetane ring D precursors. AB - A series of potential taxoid substrates was prepared in radiolabelled form to probe in vitro for the oxirane formation step and subsequent ring expansion step to the oxetane (ring D) presumably involved in the biosynthesis of the anticancer agent Taxol. None of the taxoid test substrates underwent transformation in cell free systems from Taxus suggesting that these surrogates bore substitution patterns inappropriate for recognition or catalysis by the target enzymes, or that taxoid oxiranes and oxetanes arise by independent biosynthetic pathways. PMID- 20305724 TI - Reactive species and pulmonary edema. AB - Pulmonary edema occurs when fluid flux into the lung interstitium exceeds its removal, resulting in hypoxemia and even death. Noncardiogenic pulmonary edema (NPE) generally results when microvascular and alveolar permeability to plasma proteins increase, one possible etiology being oxidant injury. Reactive oxygen and nitrogen species (RONS) can modify or damage ion channels, such as epithelial sodium channels, which alters fluid balance. Experimental systems in which either RONS are increased or protective antioxidant mechanisms are decreased result in alterations of epithelial sodium channel activity and support the hypothesis that RONS are important in NPE. Both basic and clinical studies are needed to critically define the RONS-NPE connection and the capacity of antioxidant therapy (either alone or as a supplement to beta-agonists) to improve patient outcome. PMID- 20305725 TI - Production of Ag nanocubes on a scale of 0.1 g per batch by protecting the NaHS mediated polyol synthesis with argon. AB - Au nanocages synthesized from Ag nanocubes via the galvanic replacement reaction are finding widespread use in a range of applications because of their tunable optical properties. Most of these applications require the use of nanocages with a uniform size and in large quantities. This requirement translates into a demand for scaling up the production of Ag nanocubes with uniform, well-controlled sizes. Here we report such a method based on the modification of NaHS-mediated polyol synthesis with argon protection for fast reduction, which allows for the production of Ag nanocubes on a scale of 0.1 g per batch. The Ag nanocubes had an edge length tunable from 25 to 45 nm together with a size variation within +/-5 nm. The use of argon protection was the key to the success of this scale-up synthesis, suggesting the importance of controlling oxidative etching during synthesis. PMID- 20305726 TI - Anterior-segment imaging for assessment of glaucoma. AB - This article summarizes the physics, technology and clinical application of ultrasound biomicroscopy (UBM) and optical coherence tomography (OCT) for assessment of the anterior segment in glaucoma. UBM systems use frequencies ranging from approximately 35 to 80 MHz, as compared with typical 10-MHz systems used for general-purpose ophthalmic imaging. OCT systems use low-coherence, near infrared light to provide detailed images of anterior segment structures at resolutions exceeding that of UBM. Both technologies allow visualization of the iridocorneal angle and, thus, can contribute to the diagnosis and management of glaucoma. OCT systems are advantageous, being noncontact proceedures and providing finer resolution than UBM, but UBM systems are superior for the visualization of retroiridal structures, including the ciliary body, posterior chamber and zonules, which can provide crucial diagnostic information for the assessment of glaucoma. PMID- 20305728 TI - Intra-individual Change in Personality Stability and Age. AB - The stability of individual differences in personality traits is typically examined at the group level with test-retest correlations across two assessments. For 684 subjects (age range 17-76) we computed individual coefficients from three sequential assessments to evaluate intra-individual (i.e., within-person) change in stability over time. For both trait and profile (ipsative) stability, results indicate that intra-individual stability increases up to age 30 and then plateaus. Neither demographic variables (sex, ethnicity, education, and secular trends), nor the standing on the five major dimensions of personality, were predictors of change in trait stability. Contrary to results from studies of adolescents, personality "maturity" was unrelated to personality stability in adulthood. These findings support the notion that personality stability plateaus early in adulthood. PMID- 20305727 TI - Management of cardiovascular complications in systemic lupus erythematosus. AB - Cardiovascular disease (CVD) is a major cause of morbidity and mortality in patients with systemic lupus erythematosus (SLE). Patients with SLE have an excess risk compared with the general population; this is particularly pronounced in younger women with SLE who have an excess risk of over 50-fold compared with population controls. There is a higher prevalence of subclinical atherosclerosis in patients with SLE compared with controls, as demonstrated by a variety of imaging modalities discussed in this review. The causality of the excess risk of CVD and subclinical atherosclerosis is multifactorial in patients with SLE. While traditional risk factors play a role, after controlling for the traditional Framingham risk factors, the excess risk is still 7.5-fold greater than the general population. This review will also cover novel cardiovascular risk factors and some SLE-specific variables that contribute to CVD risk. This review discusses the risk factor modification and the evidence available for treatment of these risk factors in SLE. There have not yet been any published randomized, controlled trials in patients with SLE with respect to CVD risk factor modifications. Thus, the treatment and management recommendations are based largely on published guidelines for other populations at high risk for CVD. PMID- 20305730 TI - Generalized empirical likelihood methods for analyzing longitudinal data. AB - Efficient estimation of parameters is a major objective in analyzing longitudinal data. We propose two generalized empirical likelihood based methods that take into consideration within-subject correlations. A nonparametric version of the Wilks theorem for the limiting distributions of the empirical likelihood ratios is derived. It is shown that one of the proposed methods is locally efficient among a class of within-subject variance-covariance matrices. A simulation study is conducted to investigate the finite sample properties of the proposed methods and compare them with the block empirical likelihood method by You et al. (2006) and the normal approximation with a correctly estimated variance-covariance. The results suggest that the proposed methods are generally more efficient than existing methods which ignore the correlation structure, and better in coverage compared to the normal approximation with correctly specified within-subject correlation. An application illustrating our methods and supporting the simulation study results is also presented. PMID- 20305729 TI - Implementation of molecular dynamics and its extensions with the coarse-grained UNRES force field on massively parallel systems; towards millisecond-scale simulations of protein structure, dynamics, and thermodynamics. AB - We report the implementation of our united-residue UNRES force field for simulations of protein structure and dynamics with massively parallel architectures. In addition to coarse-grained parallelism already implemented in our previous work, in which each conformation was treated by a different task, we introduce a fine-grained level in which energy and gradient evaluation are split between several tasks. The Message Passing Interface (MPI) libraries have been utilized to construct the parallel code. The parallel performance of the code has been tested on a professional Beowulf cluster (Xeon Quad Core), a Cray XT3 supercomputer, and two IBM BlueGene/P supercomputers with canonical and replica exchange molecular dynamics. With IBM BlueGene/P, about 50 % efficiency and 120 fold speed-up of the fine-grained part was achieved for a single trajectory of a 767-residue protein with use of 256 processors/trajectory. Because of averaging over the fast degrees of freedom, UNRES provides an effective 1000-fold speed-up compared to the experimental time scale and, therefore, enables us to effectively carry out millisecond-scale simulations of proteins with 500 and more amino-acid residues in days of wall-clock time. PMID- 20305731 TI - Understanding Adolescent Delinquency: The Role of Older Siblings' Delinquency and Popularity with Peers. AB - The present study examined delinquency concordance and the moderating effects of younger sibling perceptions of older sibling popularity in a sample of 587 adolescent sibling pairs. Using a social learning framework, and taking dyad composition into account, perceptions of popularity were hypothesized to strengthen siblings' concordance for delinquency. Older sibling delinquency significantly predicted younger sibling delinquency. Older sibling popularity was not important in predicting boys' delinquency. However, perceptions of older sibling popularity directly predicted reduced delinquency for girls with older sisters. A significant interaction effect was found for girls with older brothers. Older brother delinquency predicted girls' delinquency for girls who perceived their older brother to be relatively popular. There was no delinquency concordance for girls who perceived their older brothers to be less popular. PMID- 20305732 TI - Functional activities and immunohistochemical cellular distribution of glutathione s-transferases in normal, dysplastic, and squamous cell carcinoma human oral tissues. AB - Clinical data show a strong correlation between tobacco and alcohol use and the development of oral squamous cell carcinoma (SCC). While this association implies that the oral mucosa actively metabolizes carcinogens, there is little information which depicts the carcinogen metabolizing enzymes within the oral cavity. Glutathione S-transferases (GSTs) primary function is to detoxify carcinogens by increasing their water solubility, GSTs represent key carcinogen metabolizing enzymes. Notably, individuals with a null phenotype for certain GST isoforms are at an increased risk to develop cancer. This study investigated the function and distribution of GSTs in human oral tissues. Our results from this pilot study showed a trend towards higher GST activities in SCC tissues relative to normal mucosa. Also, relative to normal tissues, the SCC and epithelial dysplasia samples showed a more intense and uniform GST intracellular distribution. GST activities are increased in many high grade cancers. Similarly, our data suggest that GST upregulation occurs in at least a subset of precancerous and malignant oral lesions. PMID- 20305733 TI - Viable cell sorting of dinoflagellates by multiparametric flow cytometry. AB - Electronic cell sorting for isolation and culture of dinoflagellates and other marine eukaryotic phytoplankton was compared to the traditional method of manually picking cells using a micropipette. Trauma to electronically sorted cells was not a limiting factor, as fragile dinoflagellates, such as Karenia brevis (Dinophyceae), survived electronic cell sorting to yield viable cells. The rate of successful isolation of large-scale (> 4 litres) cultures was higher for manual picking than for electronic cell sorting (2% vs 0.5%, respectively). However, manual picking of cells is more labor intensive and time consuming. Most manually isolated cells required repicking, as the cultures were determined not to be unialgal after a single round of isolation; whereas, no cultures obtained in this study from electronic single-cell sorting required resorting. A broad flow cytometric gating logic was employed to enhance species diversity. The percentages of unique genotypes produced by manual picking or electronic cell sorting were similar (57% vs 54%, respectively), and each approach produced a variety of dinoflagellate or raphidophyte genera. Alternatively, a highly restrictive gating logic was successfully used to target K. brevis from a natural bloom sample. Direct electronic single-cell sorting was more successful than utilizing a pre-enrichment sort followed by electronic single-cell sorting. The appropriate recovery medium may enhance the rate of successful isolations. Seventy percent of isolated cells were recovered in a new medium (RE) reported here, which was optimized for axenic dinoflagellate cultures. The greatest limiting factor to the throughput of electronic cell sorting is the need for manual postsort culture maintenance and assessment of the large number of isolated cells. However, when combined with newly developed automated methods for growth screening, electronic single-cell sorting has the potential to accelerate the discovery of new algal strains. PMID- 20305734 TI - Type-zero copper proteins. AB - Many proteins contain copper in a range of coordination environments, where it has various biological roles, such as transferring electrons or activating dioxygen. These copper sites can be classified by their function or spectroscopic properties. Those with a single copper atom are either type 1, with an intense absorption band near 600 nm, or type 2, with weak absorption in the visible region. We have built a novel copper(II) binding site within structurally modified Pseudomonas aeruginosa azurins that does not resemble either existing type, which we therefore call 'type zero'. X-ray crystallographic analysis shows that these sites adopt distorted tetrahedral geometries, with an unusually short Cu-O (G45 carbonyl) bond. Relatively weak absorption near 800 nm and narrow parallel hyperfine splittings in electron paramagnetic resonance spectra are the spectroscopic signatures of type zero copper. Cyclic voltammetric experiments demonstrate that the electron transfer reactivities of type-zero azurins are enhanced relative to that of the corresponding type 2 (C112D) protein. PMID- 20305735 TI - Choice, conditioned reinforcement, and the prius effect. AB - Psychologists have long been intrigued with the rationales that underlie our decisions. Similarly, the concept of conditioned reinforcement has a venerable history, particularly in accounting for behavior not obviously maintained by primary reinforcers. The studies of choice and of conditioned reinforcement have often developed in lockstep. Many contemporary approaches to these fundamental topics share an emphasis on context and on relative value. We trace the evolution of thinking about the potency of conditioned reinforcers from stimuli that were thought to acquire their value from pairings with more fundamental reinforcers to stimuli that acquire their value by being differentially correlated with these more fundamental reinforcers. We discuss some seminal experiments (including several that have been underappreciated) and some ongoing data, all of which have propelled us to the conclusion that the strength of conditioned reinforcers is determined by their signaling a relative improvement in the organism's relation to reinforcement. PMID- 20305737 TI - Singular Value Decomposition-based Alternative Splicing Detection. AB - Altered alternative splicing has been identified as an important factor in tumorigenesis. The Affymetrix exon tiling array is designed for detecting alternative splicing events in a transcriptome-wide fashion; however, there are currently few analysis tools that are well studied for effective detection of alternative splicing events. We propose a new screening procedure based on singular value decomposition (SVD) of the residual matrix from a robust additive model fit to probe selection region (PSR) data. With this approach, we analyze the exon tiling array data from a brain cancer study conducted at the M. D. Anderson Cancer Center, and show that the proposed SVD-based approach is able to better accommodate outlying measures and capitalize on the multidimensional group by-PSR gene expression profiles for more effective detection of group-specific alternative splicing events as well as the PSRs that are most likely associated with the alternative splicing. Lab validation confirmed some of our findings, but the list of candidates detected with our proposed method may provide a better signpost to guide further investigations. PMID- 20305738 TI - Multifunctional Nanoparticles as Biocompatible Targeted Probes for Human Cancer Diagnosis and Therapy. AB - The use of nanoparticles in biological application has been rapidly advancing toward practical applications in human cancer diagnosis and therapy. Upon linking the nanoparticles with biomolecules, they can be used to locate cancerous area as well as for traceable drug delivery with high affinity and specificity. In this review, we discuss the engineering of multifunctional nanoparticle probes and their use in bioimaging and nanomedicine. PMID- 20305739 TI - Non-parametric estimation of bivariate failure time associations in the presence of a competing risk. AB - Most research on the study of associations among paired failure times has either assumed time invariance or been based on complex measures or estimators. Little has accommodated competing risks. This paper targets the conditional cause specific hazard ratio, henceforth called the cause-specific cross ratio, a recent modification of the conditional hazard ratio designed to accommodate competing risks data. Estimation is accomplished by an intuitive, non-parametric method that localizes Kendall's tau. Time variance is accommodated through a partitioning of space into 'bins' between which the strength of association may differ. Inferential procedures are developed, small-sample performance is evaluated and the methods are applied to the investigation of familial association in dementia onset. PMID- 20305736 TI - Biomarkers of Psychological Stress in Health Disparities Research. AB - Psychological stress can contribute to health disparities in populations that are confronted with the recurring stress of everyday life. A number of biomarkers have been shown to be affected by psychological stress. These biomarkers include allostatic load, which is a summary measure of the cumulative biological burden of the repeated attempts to adapt to daily stress. Allostatic load includes effects on the hypothalamic-pituitary axis, the sympathetic nervous system and the cardiovascular system. These in turn affect the immune system via bidirectional signaling pathways. Evidence is also building that psychological stress, perhaps via heightened inflammatory states, can increase oxidative stress levels and DNA damage. The inter-relationships of ethnicity, genotype, gene expression and ability to adequately mitigate stress response are just starting to be appreciated. The need to conduct these studies in disadvantaged populations is clear and requires methods to address potential logistical barriers. Biomarkers can help characterize and quantify the biological impact of psychological stress on the etiology of health disparities. PMID- 20305741 TI - The value of victory: social origins of the winner's curse in common value auctions. AB - Auctions, normally considered as devices facilitating trade, also provide a way to probe mechanisms governing one's valuation of some good or action. One of the most intriguing phenomena in auction behavior is the winner's curse - the strong tendency of participants to bid more than rational agent theory prescribes, often at a significant loss. The prevailing explanation suggests that humans have limited cognitive abilities that make estimating the correct bid difficult, if not impossible. Using a series of auction structures, we found that bidding approaches rational agent predictions when participants compete against a computer. However, the winner's curse appears when participants compete against other humans, even when cognitive demands for the correct bidding strategy are removed. These results suggest the humans assign significant future value to victories over human but not over computer opponents even though such victories may incur immediate losses, and that this valuation anomaly is the origin of apparently irrational behavior. PMID- 20305740 TI - Surgical and Interventional Robotics: Part III: Surgical Assistance Systems. PMID- 20305742 TI - Structural rearrangements in a lamellar diblock copolymer thin film during treatment with saturated solvent vapor. AB - We have investigated the structural changes in thin films of lamellar poly(styrene-b-butadiene) diblock copolymers during treatment with saturated cyclohexane vapor, a solvent slightly selective for polybutadiene. Using real time, in-situ grazing-incidence small-angle X-ray scattering (GISAXS), the swelling and the rearrangement of the lamellae were investigated with a time resolution of a few seconds, and the underlying processes on the molecular level were identified. After a few minutes in vapor, a transient state with a more well defined and more long-range ordered lamellar orientation was encountered. Additional parallel lamellae formed which we attribute to the increased degree of coiling of the polymers in the swollen state. Eventually, the film became disordered. These changes are attributed to the increased mobility of the swollen polymers and the gradually decreasing segment-segment interaction parameter in the film as solvent is absorbed. PMID- 20305743 TI - Boundary Recovery For Delaunay Tetrahedral Meshes Using Local Topological Transformations. AB - Numerous high-quality, volume mesh-generation systems exist. However, no strategy can address all geometry situations without some element qualities being compromised. Many 3D mesh generation algorithms are based on Delaunay tetrahedralization which frequently fails to preserve the input boundary surface topology. For biomedical applications, this surface preservation can be critical as they usually contain multiple material regions of interest coherently connected. In this paper we present an algorithm as a post-processing method that optimizes local regions of compromised element quality and recovers the original boundary surface facets (triangles) regardless of the original mesh generation strategy. The algorithm carves out a small sub-volume in the vicinity of the missing boundary facet or compromised element, creating a cavity. If the task is to recover a surface boundary facet, a natural exit hole in the cavity will be present. This hole is patched with the missing boundary surface face first followed by other patches to seal the cavity. If the task was to improve a compromised region, then the cavity is already sealed. Every triangular facet of the cavity shell is classified as an active face and can be connected to another shell node creating a tetrahedron. In the process the base of the tetrahedron is removed from the active face list and potentially 3 new active faces are created. This methodology is the underpinnings of our last resort method. Each active face can be viewed as the trunk of a tree. An exhaustive breath and depth search will identify all possible tetrahedral combinations to uniquely fill the cavity. We have streamlined this recursive process reducing the time complexity by orders of magnitude. The original surfaces boundaries (internal and external) are fully restored and the quality of compromised regions improved. PMID- 20305744 TI - Effect of a soluble surfactant on a finite sized bubble motion in a blood vessel. AB - We present detailed results for the motion of a finite sized gas bubble in a blood vessel. The bubble (dispersed phase) size is taken to be such as to nearly occlude the vessel. The bulk medium is treated as a shear thinning Casson fluid and contains a soluble surfactant that adsorbs and desorbs from the interface. Three different vessel sizes, corresponding to a small artery, a large arteriole, and a small arteriole, in normal humans, are considered. The hematocrit (volume fraction of RBCs) has been taken to be 0.45. For arteriolar flow, where relevant, the Fahraeus-Lindqvist effect is taken into account. Bubble motion cause temporal and spatial gradients of shear stress at the cell surface lining the vessel wall as the bubble approaches the cell, moves over it and passes it by. Rapid reversals occur in the sign of the shear stress imparted to the cell surface during this motion. Shear stress gradients together with sign reversals are associated with a recirculation vortex at the rear of the moving bubble. The presence of the surfactant reduces the level of the shear stress gradients imparted to the cell surface as compared to an equivalent surfactant-free system. Our numerical results for bubble shapes and wall shear stresses may help explain phenomena observed in experimental studies related to gas embolism, a significant problem in cardiac surgery and decompression sickness. PMID- 20305746 TI - Accounting for accountability: a discourse analysis of psychiatric nurses' experience of a patient suicide. AB - Whilst the experience of a patient suicide is likely to have a significant impact upon the nurses who had been providing care, little work has actually explored this experience in any depth. In this article we explore how two psychiatric nurses construct and orient to accountability when talking of their experiences of a patient suicide. Discourse analysis was used to explore particular phases that the nurses oriented to in their accounts: scene setting; risk assessment; attributing for the suicide. Findings highlight the different, sometimes contradictory, ways the nurses attended to interactional concerns relating to implicit accountability and potential inferences of blame. Analysis of the nurses' talk can make a valuable contribution to understanding the nature and the impact of 'accountability' in a mental health setting and so help nurses and other professionals gain an insight into their practice. The results from this study suggest that as a consequence of internalising fundamentally unrealisable expectations regarding suicide prevention, nurses can hold themselves to blame raising significant concerns around their needs in terms of support, which may not be recognised. This paper also makes a valuable contribution to our methodological understanding and the value of using discourse analysis in this setting. PMID- 20305745 TI - Expanded network of inflammatory markers of atherogenesis: where are we now? AB - Inflammatory biomarkers play a pivotal role in atherosclerotic lesions. The plasma levels of these markers are predictive of adverse outcomes such as myocardial infarction and cardiovascular death. The immune system is involved at all stages of atherogenesis via activation of monocytes/macrophages and T lymphocytes. Circulating proinflammatory cytokines and chemokines produced by these cells interact with specific receptors on various cells and activate specific signaling pathways, leading to inflammation-induced atherosclerotic lesions. Recent studies have focused on predictive value of inflammatory biomarkers such as C-reactive protein and interleukin-6. These biomarkers were shown to be associated with poor quality of life and predictive of adverse events in coronary atherosclerosis and left ventricular dysfunction. Vascular predictive value of other numerous inflammatory markers is being investigated. We herein analyze the role of several mediators of inflammation, affecting vascular functions and leading toward atherosclerotic lesions. PMID- 20305747 TI - The foundations of neuroanthropology. PMID- 20305748 TI - Neuroanthropology: evolution and emotional embodiment. AB - The Decade of the Mind is a proposal for a research initiative focused on four areas of neuroscience, including mental health, high-level cognitive function, education, and computational applications. Organizing efforts to date have primarily included cognitive scientists, computer scientists, and engineers, as well as physicians. At the same time anthropologists have started to explore the implications of neuroscience for understanding culture. Here we suggest that evolutionary neuroscience can be used to bridge knowledge obtained by social scientists with that obtained in the neurosciences for a more complete appreciation of the mind. We consider such a perspective as neuroanthropology. We use embodiment, an anthropological concept that has been substantiated by recent findings in neuroscience, to illustrate an integrative biocultural approach within neuroanthropology and suggest future possible directions for research. PMID- 20305749 TI - Salt content in canteen and fast food meals in Denmark. AB - BACKGROUND: A high salt (=NaCl) intake is associated with high blood pressure, and knowledge of salt content in food and meals is important, if the salt intake has to be decreased in the general population. OBJECTIVE: To determine the salt content in worksite canteen meals and fast food. DESIGN: For the first part of this study, 180 canteen meals were collected from a total of 15 worksites with in house catering facilities. Duplicate portions of a lunch meal were collected from 12 randomly selected employees at each canteen on two non-consecutive days. For the second part of the study, a total of 250 fast food samples were collected from 52 retail places representing both city (Aarhus) and provincial towns. The canteen meals and fast food samples were analyzed for chloride by potentiometric titration with silver nitrate solution, and the salt content was estimated. RESULTS: The salt content in lunch meals in worksite canteens were 3.8+/-1.8 g per meal and 14.7+/-5.1 g per 10 MJ for men (n=109), and 2.8+/-1.2 g per meal and 14.4+/-6.2 g per 10 MJ for women (n=71). Salt content in fast food ranged from 11.8+/-2.5 g per 10 MJ (burgers) to 16.3+/-4.4 g per 10 MJ (sausages) with a mean content of 13.8+/-3.8 g per 10 MJ. CONCLUSION: Salt content in both fast food and in worksite canteen meals is high and should be decreased. PMID- 20305750 TI - Chemoenzymatic Syntheses of Tumor-Associated Carbohydrate Antigen Globo-H and Stage-Specific Embryonic Antigen 4. AB - Gangliosides have attracted much attention due to their important biological properties. Herein, we report the first chemoenzymatic syntheses of two globo series of ganglioside oligosaccharides, Globo-H 1 and stage-specific embryonic antigen-4 (SSEA-4) 2. The common precursor SSEA-3 pentasaccharide for these two compounds was assembled rapidly using the pre-activation based one-pot glycosylation method. The stereoselectivity in forming the 1,2-cis linkage in SSEA-3 was attributed to a steric buttressing effect of the donor rather than electronic properties of the glycosyl donors. SSEA-3 was then successfully fucosylated by the fucosyltransferase WbsJ and sialylated by sialyltransferases CST-I and PmST1 producing Globo-H and SSEA-4 respectively. PMID- 20305751 TI - Dendritic bundles, minicolumns, columns, and cortical output units. AB - THE SEARCH FOR THE FUNDAMENTAL BUILDING BLOCK OF THE CEREBRAL CORTEX HAS HIGHLIGHTED THREE STRUCTURES, PERPENDICULAR TO THE CORTICAL SURFACE: (i) columns of neurons with radially invariant response properties, e.g., receptive field position, sensory modality, stimulus orientation or direction, frequency tuning etc., (ii) minicolumns of radially aligned cell bodies and (iii) bundles, constituted by the apical dendrites of pyramidal neurons with cell bodies in different layers. The latter were described in detail, and sometimes quantitatively, in several species and areas. It was recently suggested that the dendritic bundles consist of apical dendrites belonging to neurons projecting their axons to specific targets. We review the concept above and suggest that another structural and computational unit of cerebral cortex is the cortical output unit, i.e., an assembly of bundles of apical dendrites and their parent cell bodies including each of the outputs to distant cortical or subcortical structures, of a given cortical locus (area or part of an area). This somato dendritic assembly receives inputs some of which are common to the whole assembly and determine its radially invariant response properties, others are specific to one or more dendritic bundles, and determine the specific response signature of neurons in the different cortical layers and projecting to different targets. PMID- 20305752 TI - Behavioral and neurobiological changes in C57BL/6 mouse exposed to cuprizone: effects of antipsychotics. AB - Recent human studies suggest a role for altered oligodendrocytes in the pathophysiology of schizophrenia. Our recent animal study has reported some schizophrenia-like behaviors in mice exposed to cuprizone (Xu et al., 2009), a copper chelator that has been shown to selectively damage the white matter. This study was to explore mechanisms underlying the behavioral changes in cuprizone exposed mice and to examine effects of the antipsychotics haloperidol, clozapine and quetiapine on the changes in the mice. Mice given cuprizone for 14 days showed a deficit in the prepulse inhibition of acoustic startle response and higher dopamine in the prefrontal cortex (PFC), which changes were not seen in mice given cuprizone plus antipsychotics. Mice given cuprizone for 21 days showed lower spontaneous alternations in Y-maze, which was not seen in mice treated with cuprizone plus the antipsychotics. Mice given cuprizone for 28 days displayed less social interactions, which was not seen in mice given cuprizone plus clozapine/quetiapine, but was seen in mice given cuprizone plus haloperidol. Mice given cuprizone for 42 days showed myelin sheath loss and lower myelin basic protein in PFC, caudate putamen, and hippocampus. The white matter damage in PFC was attenuated in mice given cuprizone plus clozapine/haloperidol. But the white matter damage in caudate putamen and hippocampus was only attenuated by clozapine and quetiapine, not by haloperidol. These results help us to understand the behavioral changes and provide experimental evidence for the protective effects of antipsychotics on white matter damage in cuprizone-exposed mice. PMID- 20305753 TI - Graded representations of emotional expressions in the left superior temporal sulcus. AB - Perceptual categorization is a fundamental cognitive process that gives meaning to an often graded sensory environment. Previous research has subdivided the visual pathway into posterior regions that processes the physical properties of a stimulus, and frontal regions that process more abstract properties such as category information. The superior temporal sulcus (STS) is known to be involved in face and emotion perception, but the nature of its processing remains unknown. Here, we used targeted fMRI measurements of the STS to investigate whether its representations of facial expressions are categorical or noncategorical. Multivoxel pattern analysis showed that even though subjects were performing a categorization task, the left STS contained graded, noncategorical representations. In the right STS, representations showed evidence for both stimulus-related gradations and a categorical boundary. PMID- 20305754 TI - Nutritient intake of young children with Prader-Willi syndrome. AB - BACKGROUND: Prader-Willi syndrome (PWS) is a rare genetic disorder resulting in obesity. The diets for young children with PWS must balance the importance of preventing development of obesity with the need to supply sufficient energy and essential nutrients. OBJECTIVE: To investigate the nutritional intake for children with PWS 2, 3, and 4 years of age and compare it with Nordic Nutritional Recommendations (NNR) and intake of healthy controls. DESIGN: Assessments of food intake for six children 2-4 years of age were performed twice a year. At the age of 2 and 3 years data was obtained by using food recall interviews and at 4 year of age a pre-coded food-diary was used. RESULTS: The energy intake for the 2-year old children was 3.25 MJ/day (SD 0.85) and for the 3- and 4-year olds 3.62 MJ/day (SD 0.73) and 4.07 MJ/day (SD 0.39 MJ), respectively. These intakes are 61%, 68%, and 77% of the estimated energy requirements in NNR for healthy 2-, 3- and 4-year old children, respectively, and 60% and 66% of the energy intakes of 2- and 4 year-old children in reference populations. The children's BMI-for-age score and length growth was within the normal range during the study period. The intake of fat was about 25 E% in all age groups and reduced when compared with reference populations. In 25% of the assessments the fat intake was 20 E% or below. The intake of iron was below recommendations in all age groups both with and without supplementation. The mean intake of vitamin D and tocopherol was below recommendations when intakes were determined excluding dietary supplementations. CONCLUSIONS: More large-scale investigations on nutritional intake are needed to further investigate dietary challenges for this patient group. PMID- 20305755 TI - Hebbian Reweighting on Stable Representations in Perceptual Learning. AB - Perceptual learning is the improvement in perceptual task performance with practice or training. The observation of specificity in perceptual learning has been widely associated with plasticity in early visual cortex representations. Here, we review the evidence supporting the plastic reweighting of readout from stable sensory representations, originally proposed by Dosher & Lu (1998), as an alternative explanation of perceptual learning. A task-analysis that identifies circumstances in which specificity supports representation enhancement and those in which it implies reweighting provides a framework for evaluating the literature; reweighting is broadly consistent with the behavioral results and almost all of the physiological reports. We also consider the evidence that the primary mode of perceptual learning is through augmented Hebbian learning of the reweighted associations, which has implications for the role and importance of feedback. Feedback is not necessary for perceptual learning, but can improve it in some circumstances, and in some cases block feedback is also helpful - all effects that are generally compatible with an augmented Hebbian model (Petrov, Dosher, & Lu, 2005). The two principles of perceptual learning through reweighting evidence from stable sensory representations and of augmented Hebbian learning provide a theoretical structure for the consideration of issues such as task difficulty, task roving, and cuing in perceptual learning. PMID- 20305756 TI - Tumor and liver determinants of prognosis in unresectable hepatocellular carcinoma: a large case cohort study. AB - OBJECTIVES: 967 patients with unresectable and untransplantable, biopsy-proven hepatocellular carcinoma (HCC) were prospectively evaluated at baseline and followed up till death. Survival was the end point. RESULTS: We found that male gender, ascites, cirrhosis, portal vein thrombosis (PVT), elevated AFP or bilirubin, or alkaline phosphatase, were each statistically significant adverse prognostic factors. Patients with normal AFP survived longer than those with elevated AFP, even in the presence of PVT, large or bilobar tumors or cirrhosis. We used a bivariate analysis to separate patient sub groups based on liver function and tumor characteristics and found clear discrimination in survival between subsets; in addition both cirrhosis and presence of PVT were significant factors. We also used a purely mathematical approach to derive subgroups and a prognostic model for individual patients. Interestingly, the two approaches gave similar predictive information, which opens the possibility of a more detailed mathematical analysis in the future. The results of this large dataset show that amongst non-surgical HCC patients, there are clear subsets with longer survival. CONCLUSION: The data supports the concept of heterogeneity of HCC. The three factors, bilirubin, AFP, and PVT predominate in prognosis. PMID- 20305757 TI - Fatty liver disease in children: eat now pay later. AB - INTRODUCTION: With the recent epidemic in childhood obesity, nonalcoholic fatty liver disease (NAFLD) has become an emerging problem and a common cause of chronic liver disease in children. METHODS: In this review, the most recent insights on the pathogenesis, diagnosis, natural history, and treatment of NAFLD in children are discussed. PMID- 20305759 TI - Outcomes for patients following hepatic resection of metastatic tumors from gastric cancer. AB - PURPOSE: Although several studies have reported the efficacy of hepatic resection for the long-term survival of patients with gastric cancer metastases, the optimal treatment remains to be determined. METHODS: Seventeen patients underwent a hepatic resection for gastric cancer metastases at the National Defense Medical College Hospital. We retrospectively analyzed the clinical outcomes of surgical resection and identified factors associated with prognosis for patients who underwent hepatectomy for gastric cancer metastases. RESULTS: In 17 patients, the accumulated 5-year survival rate after hepatic resection was 31.5% and the median survival time was 34 months. Univariate and multivariate analyses showed that gastric tumors less than 6.0 cm and D2 lymphadenectomy were the most important predictors of survival. The five patients who survived more than 5 years after hepatic resection had a D2 lymphadenectomy, modest lymphatic invasion, primary gastric tumors less than 6.0 cm, and a solitary liver metastasis. CONCLUSION: Although recent progress in adjuvant therapy should be the key to a good prognosis, we believe that surgical resection may bring some hope of long-term survival for judiciously selected patients with hepatic metastases from gastric cancer. PMID- 20305758 TI - Chronic hepatitis B: whom to treat and for how long? Propositions, challenges, and future directions. AB - Recent guidelines of the American Association for the Study of Liver Diseases, the European Association for the Study of the Liver, and the Asian Pacific Association for the Study of the Liver 2008 update of the "Asian-Pacific consensus statement on the management of chronic hepatitis B" offer comprehensive recommendations for the general management of chronic hepatitis B (CHB). These recommendations highlight preferred approaches to the prevention, diagnosis, and treatment of CHB. Nonetheless, the results of recent studies have led to an improved understanding of the disease and a belief that current recommendations on specific therapeutic considerations, including CHB treatment initiation and cessation criteria, particularly in patient populations with special circumstances, can be improved. Twelve experts from the Asia-Pacific region formed the Asia-Pacific Panel Recommendations for the Optimal Management of Chronic Hepatitis B (APPROACH) Working Group to review, challenge, and assess relevant new data and inform future updates of CHB treatment guidelines. The significance of and controversy about reported findings were discussed and debated in an expert meeting of the Working Group in Beijing, China, in November 2008. This review paper attempts to identify areas requiring improved CHB management and provide suggestions for future guideline updates, with special emphasis on treatment initiation and duration. PMID- 20305760 TI - Efficacy and resistance of entecavir following 3 years of treatment of Japanese patients with lamivudine-refractory chronic hepatitis B. AB - PURPOSE: Lamivudine treatment of chronic hepatitis B (CHB) is associated with frequent resistance and loss of clinical benefit. We present outcomes of lamivudine-refractory Japanese patients treated with entecavir for 3 years. METHODS: Eighty-two patients refractory to lamivudine therapy received entecavir 0.5 or 1 mg daily for 52 weeks in phase II study ETV-052, directly entered rollover study ETV-060, and received entecavir 1 mg daily. Responses were evaluated among patients with available samples. RESULTS: After 96 weeks in ETV 060 (148 weeks total entecavir treatment time), 55%(36/65) of patients had hepatitis B virus(HBV) DNA of?400 copies/mL, 85% (52/61) had alanine aminotransferase (ALT) of <=1 * upper limit of normal (ULN), and 14.6% (7/48) achieved HBe seroconversion.A subset of 42 patients received entecavir 1 mg from phase II baseline through 148 weeks: 54% (19/35) had HBV DNA of <400 copies/mL, 84% (27/32) had ALT of <=1 * ULN, and 15% (4/27) achieved HBe seroconversion.Sixteen patients in the 1-mg subset had baseline and week 148 evaluable biopsy pairs: 81% (13/16) showed histologic improvement and 38% (6/16) showed improvement in fibrosis. Genotypic resistance to entecavir emerged in 31 patients for a 3-year cumulative resistance probability of 35.9%. Entecavir was generally well tolerated during ETV-060, with no on-treatment ALT flares. CONCLUSIONS: Long-term entecavir treatment of lamivudine-refractory CHB resulted in virologic suppression, ALT normalization, and improvements in liver histology. Resistance was consistent with that observed in worldwide studies. PMID- 20305761 TI - Clinicopathological significance of RASSF1A reduced expression and hypermethylation in hepatocellular carcinoma. AB - PURPOSE: Protein downregulation and hypermethylation of Ras association domain family 1A (RASSF1A) has been recognized as an important early event in different classes of carcinogenesis, but clinicopathological significance of RASSF1A protein expression and methylation in hepatocellular carcinoma (HCC) remains largely unknown. The aim of the study was to investigate the expression of RASSF1A protein and methylation in HCC and their clinical significance. METHODS: Immunohistochemistry was employed to detect the expression of RASSF1A proteins in liver tissue microarrays. Aberrant promoter hypermethylation of RASSF1A was investigated in DNA from HCC, matching noncancerous tissues and serum of 35 HCC patients by methylation-specific PCR. RESULTS: RASSF1A protein expression in HCC was significantly lower than that in noncancerous (p = 0.015) and paracancerous tissues (p = 0.017). In addition, reduced RASSF1A protein expression is related to TNM stage, metastasis, alpha-fetoprotein, portal vein embolus, capsular infiltration, and multiple tumor nodes. Furthermore, RASSF1A promoter methylation in HCC was significantly higher than that in noncancerous liver tissues (p < 0.05). Meanwhile, RASSF1A promoter hypermethylation was detected in 14 in the serum DNA from HCC patients, whereas no hypermethylation was detected in the normal controls. Hypermethylation of RASSF1A in HCC serum and tissues was negatively correlated with the expression of RASSF1A protein expression (p < 0.05). CONCLUSIONS: The loss or abnormal protein downregulation and the promoter hypermethylation of RASSF1A could play important roles in the tumorigenesis development and metastases of HCC. The detection of the promoter hypermethylation of RASSF1A in serum DNA could be a valuable biomarker for early-stage diagnosis in populations at high risk of HCC. PMID- 20305762 TI - Deep vein thrombosis in patients with advanced liver cirrhosis: a rare condition? AB - PURPOSE: Patients with liver cirrhosis are generally considered to be "auto anticoagulated" because of coagulopathy and thrombocytopenia. However, deep vein thrombosis (DVT) has been reported in patients with liver cirrhosis. The objectives of this study were to know the prevalence of DVT among cirrhotic patients and to compare clinical pictures between cirrhotic patients with and without DVT. METHODS: A case-control study was performed on the basis of medical record data of patients with liver cirrhosis admitted between August 2004 and July 2007 in Medistra hospital in Jakarta. Diagnosis of DVT was established by duplex Doppler ultrasonography of the lower extremities. Patients with splanchnic thrombosis were excluded from this study. Diagnosis of liver cirrhosis was based on history and clinical manifestation, consistent with liver cirrhosis and confirmed by ultrasonography or computed tomography. RESULTS: A total of 256 patients with liver cirrhosis were included in this study; 164 (64.1%) among them were men. Patients' mean age was 60.5 +/- 12.5 years, ranging from 16 to 88 years. Viral hepatitis accounted for 74.6% of patients with liver cirrhosis. DVT was found in 12 (4.7%) patients. There was no significant laboratory difference between cirrhotic patients with and without DVT (serum albumin, platelet count, aminotransferases, gamma-glutamyl transpeptidase, alkaline phosphatase, total bilirubin levels, and prothrombin time). Diabetes mellitus was significantly higher in the DVT group than that in the control group (66.6 vs. 34.0%, P = 0.025). Multivariate analysis confirmed diabetes mellitus as an independent risk factor for the occurrence of DVT (odds ratio = 4.26; 95% confidence interval = 1.206-15.034; P = 0.024). CONCLUSIONS: The prevalence of DVT in patients with liver cirrhosis was 4.7%, and Deep vein thrombosis is not a rare condition in cirrhotic patients with coagulopathy and warrants further studies on the mechanisms and prevention. PMID- 20305763 TI - Periocular plastic surgery. AB - BACKGROUND: Good vision depends on the normal anatomy and function of the eyelids and orbital structures. The goals of periocular ophthalmic plastic surgery are the anatomical and functional preservation and restoration of the lids, orbits, and periorbital structures when they are affected by congenital or acquired malpositions, defects and mass lesions. In this region, functional and esthetic considerations are closely linked. METHOD: This review is based on selected articles retrieved by a PubMed search, the guidelines of the German Ophthalmologists' Association (Bundesverband der Augenarzte, BVA) and German Ophthalmological Society (Deutsche Ophthalmologische Gesellschaft, DOG), and the authors' own clinical and scientific experience. RESULTS: The surgical correction of eyelid malpositions is based on the restoration of normal anatomy with attention to function. Eyelids are reconstructed with a combination of local flaps and free grafts, preferably from the periorbital structures. Orbital procedures are usually performed in specialized centers, by multidisciplinary surgical teams if necessary. The surgical approaches are becoming ever smaller and cosmetically less noticeable. For patients with acquired anophthalmos, the use of orbital implants is essential for optimal fitting of the prosthesis. CONCLUSION: Modern periocular plastic surgery exploits an extensive range of specialized surgical techniques to treat a wide variety of abnormalities and diseases in this region. The success of such procedures depends on thorough knowledge of the complex anatomy and physiology of these structures as well as on the surgeon's expertise in microsurgical techniques. PMID- 20305764 TI - Rare pathologies. PMID- 20305765 TI - Polymerase chain reaction. PMID- 20305766 TI - Non-tuberculous mycobacteria. PMID- 20305767 TI - Lymphoblastic neoplasia. PMID- 20305768 TI - Differences to tuberculosis. PMID- 20305769 TI - Chronic recurrent multifocal osteomyelitis. PMID- 20305770 TI - Disseminated non-tuberculous mycobacteriosis. PMID- 20305772 TI - Preferring blue light-filtering lenses. PMID- 20305774 TI - The epidemiology, etiology, diagnosis, and treatment of osteoarthritis of the knee. AB - BACKGROUND: Osteoarthritis is the most common joint disease of adults worldwide. Its incidence rises with age. Both intrinsic and extrinsic risk factors promote its development. In men aged 60 to 64, the right knee is more commonly affected; in women, the right and left knees are affected with nearly equal frequency. METHODS: The PubMed, Medline, Embase and Cochrane Library databases were selectively searched for current studies (up to September 2009; case reports excluded) on the epidemiology, etiology, diagnosis, staging, and treatment of osteoarthritis of the knee. The search terms were "gonarthrosis," "prevention," "conservative treatment," "joint preservation," "physical activity," "arthroscopy," "osteotomy," "braces," "orthoses," and "osteoarthritis knee joint." RESULTS AND CONCLUSION: Osteoarthritis is not yet a curable disease, and its pathogenesis remains unclear. The best treatment for osteoarthritis of the knee is prevention. The goal of therapy is to alleviate clinical manifestations. The therapeutic spectrum ranges from physiotherapy and orthopedic aids to pharmacotherapy and surgery. PMID- 20305775 TI - Formation of silicon-carbon bonds by photochemical irradiation of (eta C(5)H(5))Fe(CO)(2)SiR(3) and (eta-C(5)H(5))Fe(CO)(2)Me to obtain R(3)SiMe. AB - Photochemical irradiation of an equimolar mixture of (eta(5) C(5)H(5))Fe(CO)(2)SiR(3), FpSiR(3), and FpMe leads to the efficient formation of the silicon-carbon coupled product R(3)SiMe, R(3) = Me(3), Me(2)Ph, MePh(2), Ph(3), ClMe(2), Cl(2)Me, Cl(3), Me(2)Ar (Ar = C(6)H(4)X, X = F, OMe, CF(3), NMe(2). Similar chemistry occurs with related germyl and stannyl complexes at slower rates, Si > Ge> >>Sn. Substitution of an aryl hydrogen in FpSiMe(2)C(6)H(4)R' has little effect upon the rate of the reaction whereas progressive substitution of methyl groups on silicon by Cl slows the process. Also changing FpMe to FpCH(2)SiMe(3) dramatically slows the reaction as does the use of (eta(5)-C(5)Me(5))Fe(CO)(2) derivatives. A mechanism involving the initial formation of the 16e(-) intermediate (eta(5)-C(5)H(5))Fe(CO)Me followed by oxidative addition of the Fe-Si bond, accounts for the experimental results obtained. PMID- 20305776 TI - Putting culture under the 'spotlight' reveals universal information use for face recognition. AB - BACKGROUND: Eye movement strategies employed by humans to identify conspecifics are not universal. Westerners predominantly fixate the eyes during face recognition, whereas Easterners more the nose region, yet recognition accuracy is comparable. However, natural fixations do not unequivocally represent information extraction. So the question of whether humans universally use identical facial information to recognize faces remains unresolved. METHODOLOGY/PRINCIPAL FINDINGS: We monitored eye movements during face recognition of Western Caucasian (WC) and East Asian (EA) observers with a novel technique in face recognition that parametrically restricts information outside central vision. We used 'Spotlights' with Gaussian apertures of 2 degrees, 5 degrees or 8 degrees dynamically centered on observers' fixations. Strikingly, in constrained Spotlight conditions (2 degrees and 5 degrees) observers of both cultures actively fixated the same facial information: the eyes and mouth. When information from both eyes and mouth was simultaneously available when fixating the nose (8 degrees), as expected EA observers shifted their fixations towards this region. CONCLUSIONS/SIGNIFICANCE: Social experience and cultural factors shape the strategies used to extract information from faces, but these results suggest that external forces do not modulate information use. Human beings rely on identical facial information to recognize conspecifics, a universal law that might be dictated by the evolutionary constraints of nature and not nurture. PMID- 20305777 TI - New sequence variants in HLA class II/III region associated with susceptibility to knee osteoarthritis identified by genome-wide association study. AB - Osteoarthritis (OA) is a common disease that has a definite genetic component. Only a few OA susceptibility genes that have definite functional evidence and replication of association have been reported, however. Through a genome-wide association study and a replication using a total of approximately 4,800 Japanese subjects, we identified two single nucleotide polymorphisms (SNPs) (rs7775228 and rs10947262) associated with susceptibility to knee OA. The two SNPs were in a region containing HLA class II/III genes and their association reached genome wide significance (combined P = 2.43x10(-8) for rs7775228 and 6.73x10(-8) for rs10947262). Our results suggest that immunologic mechanism is implicated in the etiology of OA. PMID- 20305778 TI - FragKB: structural and literature annotation resource of conserved peptide fragments and residues. AB - BACKGROUND: FragKB (Fragment Knowledgebase) is a repository of clusters of structurally similar fragments from proteins. Fragments are annotated with information at the level of sequence, structure and function, integrating biological descriptions derived from multiple existing resources and text mining. METHODOLOGY: FragKB contains approximately 400,000 conserved fragments from 4,800 representative proteins from PDB. Literature annotations are extracted from more than 1,700 articles and are available for over 12,000 fragments. The underlying systematic annotation workflow of FragKB ensures efficient update and maintenance of this database. The information in FragKB can be accessed through a web interface that facilitates sequence and structural visualization of fragments together with known literature information on the consequences of specific residue mutations and functional annotations of proteins and fragment clusters. FragKB is accessible online at http://ubio.bioinfo.cnio.es/biotools/fragkb/. SIGNIFICANCE: The information presented in FragKB can be used for modeling protein structures, for designing novel proteins and for functional characterization of related fragments. The current release is focused on functional characterization of proteins through inspection of conservation of the fragments. PMID- 20305779 TI - Principles and determinants of G-protein coupling by the rhodopsin-like thyrotropin receptor. AB - In this study we wanted to gain insights into selectivity mechanisms between G protein-coupled receptors (GPCR) and different subtypes of G-proteins. The thyrotropin receptor (TSHR) binds G-proteins promiscuously and activates both Gs (cAMP) and Gq (IP). Our goal was to dissect selectivity patterns for both pathways in the intracellular region of this receptor. We were particularly interested in the participation of poorly investigated receptor parts.We systematically investigated the amino acids of intracellular loop (ICL) 1 and helix 8 using site-directed mutagenesis alongside characterization of cAMP and IP accumulation. This approach was guided by a homology model of activated TSHR in complex with heterotrimeric Gq, using the X-ray structure of opsin with a bound G protein peptide as a structural template.We provide evidence that ICL1 is significantly involved in G-protein activation and our model suggests potential interactions with subunits G alpha as well as G betagamma. Several amino acid substitutions impaired both IP and cAMP accumulation. Moreover, we found a few residues in ICL1 (L440, T441, H443) and helix 8 (R687) that are sensitive for Gq but not for Gs activation. Conversely, not even one residue was found that selectively affects cAMP accumulation only. Together with our previous mutagenesis data on ICL2 and ICL3 we provide here the first systematically completed map of potential interfaces between TSHR and heterotrimeric G-protein. The TSHR/Gq-heterotrimer complex is characterized by more selective interactions than the TSHR/Gs complex. In fact the receptor interface for binding Gs is a subset of that for Gq and we postulate that this may be true for other GPCRs coupling these G-proteins. Our findings support that G-protein coupling and preference is dominated by specific structural features at the intracellular region of the activated GPCR but is completed by additional complementary recognition patterns between receptor and G-protein subtypes. PMID- 20305780 TI - Distinct types of fibrocyte can differentiate from mononuclear cells in the presence and absence of serum. AB - BACKGROUND: Fibrocytes are bone-marrow derived cells, expressing both haematopoietic and stromal cell markers, which contribute to tissue repair as well as pathological fibrosis. The differentiation of fibrocytes remains poorly characterised and this has limited understanding of their biology and function. In particular two methods are used to generate fibrocytes in vitro that differ fundamentally by the presence or absence of serum. METHODOLOGY/PRINCIPAL FINDINGS: We show here that fibrocytes grown in the absence of serum (SF) differentiate more efficiently from peripheral blood mononuclear cells than CD14(+) monocytes, and respond to serum by losing their spindle-shaped fibrocyte morphology. Although fibrocytes generated in the presence of serum (SC) express the same range of markers, they differentiate more efficiently from CD14(+) monocytes and do not change their morphology in response to serum. Transcriptional analysis revealed that both types of fibrocyte are distinct from each other, fibroblasts and additional monocyte-derived progeny. The gene pathways that differ significantly between SF and SC fibrocytes include those involved in cell migration, immune responses and response to wounding. CONCLUSIONS/SIGNIFICANCE: These data show that SF and SC fibrocytes are distinct but related cell types, and suggest that they will play different roles during tissue repair and fibrosis where changes in serum proteins may occur. PMID- 20305781 TI - Estimating the potential for adaptation of corals to climate warming. AB - The persistence of tropical coral reefs is threatened by rapidly increasing climate warming, causing a functional breakdown of the obligate symbiosis between corals and their algal photosymbionts (Symbiodinium) through a process known as coral bleaching. Yet the potential of the coral-algal symbiosis to genetically adapt in an evolutionary sense to warming oceans is unknown. Using a quantitative genetics approach, we estimated the proportion of the variance in thermal tolerance traits that has a genetic basis (i.e. heritability) as a proxy for their adaptive potential in the widespread Indo-Pacific reef-building coral Acropora millepora. We chose two physiologically different populations that associate respectively with one thermo-tolerant (Symbiodinium clade D) and one less tolerant symbiont type (Symbiodinium C2). In both symbiont types, pulse amplitude modulated (PAM) fluorometry and high performance liquid chromatography (HPLC) analysis revealed significant heritabilities for traits related to both photosynthesis and photoprotective pigment profile. However, quantitative real time polymerase chain reaction (qRT-PCR) assays showed a lack of heritability in both coral host populations for their own expression of fundamental stress genes. Coral colony growth, contributed to by both symbiotic partners, displayed heritability. High heritabilities for functional key traits of algal symbionts, along with their short clonal generation time and high population sizes allow for their rapid thermal adaptation. However, the low overall heritability of coral host traits, along with the corals' long generation time, raise concern about the timely adaptation of the coral-algal symbiosis in the face of continued rapid climate warming. PMID- 20305782 TI - PARM-1 is an endoplasmic reticulum molecule involved in endoplasmic reticulum stress-induced apoptosis in rat cardiac myocytes. AB - To identify novel transmembrane and secretory molecules expressed in cardiac myocytes, signal sequence trap screening was performed in rat neonatal cardiac myocytes. One of the molecules identified was a transmembrane protein, prostatic androgen repressed message-1 (PARM-1). While PARM-1 has been identified as a gene induced in prostate in response to castration, its function is largely unknown. Our expression analysis revealed that PARM-1 was specifically expressed in hearts and skeletal muscles, and in the heart, cardiac myocytes, but not non-myocytes expressed PARM-1. Immunofluorescent staining showed that PARM-1 was predominantly localized in endoplasmic reticulum (ER). In Dahl salt-sensitive rats, high-salt diet resulted in hypertension, cardiac hypertrophy and subsequent heart failure, and significantly stimulated PARM-1 expression in the hearts, with a concomitant increase in ER stress markers such as GRP78 and CHOP. In cultured cardiac myocytes, PARM-1 expression was stimulated by proinflammatory cytokines, but not by hypertrophic stimuli. A marked increase in PARM-1 expression was observed in response to ER stress inducers such as thapsigargin and tunicamycin, which also induced apoptotic cell death. Silencing PARM-1 expression by siRNAs enhanced apoptotic response in cardiac myocytes to ER stresses. PARM-1 silencing also repressed expression of PERK and ATF6, and augmented expression of CHOP without affecting IRE-1 expression and JNK and Caspase-12 activation. Thus, PARM-1 expression is induced by ER stress, which plays a protective role in cardiac myocytes through regulating PERK, ATF6 and CHOP expression. These results suggested that PARM-1 is a novel ER transmembrane molecule involved in cardiac remodeling in hypertensive heart disease. PMID- 20305783 TI - Mesenchymal stem cells modified with a single-chain antibody against EGFRvIII successfully inhibit the growth of human xenograft malignant glioma. AB - BACKGROUND: Glioblastoma multiforme is the most lethal brain tumor with limited therapeutic options. Antigens expressed on the surface of malignant cells are potential targets for antibody-mediated gene/drug delivery. PRINCIPAL FINDINGS: In this study, we investigated the ability of genetically modified human mesenchymal stem cells (hMSCs) expressing a single-chain antibody (scFv) on their surface against a tumor specific antigen, EGFRvIII, to enhance the therapy of EGFRvIII expressing glioma cells in vivo. The growth of U87-EGFRvIII was specifically delayed in co-culture with hMSC-scFvEGFRvIII. A significant down regulation was observed in the expression of pAkt in EGFRvIII expressing glioma cells upon culture with hMSC-scFvEGFRvIII vs. controls as well as in EGFRvIII expressing glioma cells from brain tumors co-injected with hMSC-scFvEGFRvIII in vivo. hMSC expressing scFvEGFRvIII also demonstrated several fold enhanced retention in EGFRvIII expressing flank and intracranial glioma xenografts vs. control hMSCs. The growth of U87-EGFRvIII flank xenografts was inhibited by 50% in the presence of hMSC-scFvEGFRvIII (p<0.05). Moreover, animals co-injected with U87-EGFRvIII and hMSC-scFvEGFRvIII intracranially showed significantly improved survival compared to animals injected with U87-EGFRvIII glioma cells alone or with control hMSCs. This survival was further improved when the same animals received an additional dosage of hMSC-scFvEGFRvIII two weeks after initial tumor implantation. Of note, EGFRvIII expressing brain tumors co-injected with hMSCs had a lower density of CD31 expressing blood vessels in comparison with control tumors, suggesting a possible role in tumor angiogenesis. CONCLUSIONS/SIGNIFICANCE: The results presented in this study illustrate that genetically modified MSCs may function as a novel therapeutic vehicle for malignant brain tumors. PMID- 20305784 TI - Homer1a-dependent crosstalk between NMDA and metabotropic glutamate receptors in mouse neurons. AB - BACKGROUND: A large number of evidences suggest that group-I metabotropic glutamate receptors (mGluR1a, 1b, 1c, 5a, 5b) can modulate NMDA receptor activity. Interestingly, a physical link exists between these receptors through a Homer-Shank multi-protein scaffold that can be disrupted by the immediate early gene, Homer1a. Whether such a versatile link supports functional crosstalk between the receptors is unknown. METHODOLOGY/PRINCIPAL FINDINGS: Here we used biochemical, electrophysiological and molecular biological approaches in cultured mouse cerebellar neurons to investigate this issue. We found that Homer1a or dominant negative Shank3 mutants that disrupt the physical link between the receptors allow inhibition of NMDA current by group-I mGluR agonist. This effect is antagonized by pertussis toxin, but not thapsigargin, suggesting the involvement of a G protein, but not intracellular calcium stores. Also, this effect is voltage-sensitive, being present at negative, but not positive membrane potentials. In the presence of DHPG, an apparent NMDA "tail current" was evoked by large pulse depolarization, only in neurons transfected with Homer1a. Co immunoprecipitation experiments showed interaction between G-protein betagamma subunits and NMDA receptor in the presence of Homer1a and group-I mGluR agonist. CONCLUSIONS/SIGNIFICANCE: Altogether these results suggest a direct inhibition of NMDA receptor-channel by Gbetagamma subunits, following disruption of the Homer Shank3 complex by the immediate early gene Homer1a. This study provides a new molecular mechanism by which group-I mGluRs could dynamically regulate NMDA receptor function. PMID- 20305785 TI - Fatal outbreak from consuming Xanthium strumarium seedlings during time of food scarcity in northeastern Bangladesh. AB - BACKGROUND: An outbreak characterized by vomiting and rapid progression to unconsciousness and death was reported in Sylhet Distrct in northeastern Bangladesh following destructive monsoon floods in November 2007. METHODS AND FINDINGS: We identified cases presenting to local hospitals and described their clinical signs and symptoms. We interviewed patients and their families to collect illness histories and generate hypotheses about exposures associated with disease. An epidemiological study was conducted in two outbreak villages to investigate risk factors for developing illness. 76 patients were identified from 9 villages; 25% (19/76) died. Common presenting symptoms included vomiting, elevated liver enzymes, and altered mental status. In-depth interviews with 33 cases revealed that 31 (94%) had consumed ghagra shak, an uncultivated plant, in the hours before illness onset. Ghagra shak was consumed as a main meal by villagers due to inaccessibility of other foods following destructive monsoon flooding and rises in global food prices. Persons who ate this plant were 34.2 times more likely (95% CI 10.2 to 115.8, p-value<0.000) than others to develop vomiting and unconsciousness during the outbreak in our multivariate model. Ghagra shak is the local name for Xanthium strumarium, or common cocklebur. CONCLUSIONS: The consumption of Xanthium strumarium seedlings in large quantities, due to inaccessibility of other foods, caused this outbreak. The toxic chemical in the plant, carboxyatratyloside, has been previously described and eating X. strumarium seeds and seedlings has been associated with fatalities in humans and livestock. Unless people are able to meet their nutritional requirements with safe foods, they will continue to be at risk for poor health outcomes beyond undernutrition. PMID- 20305786 TI - NSs encoded by groundnut bud necrosis virus is a bifunctional enzyme. AB - Groundnut bud necrosis virus (GBNV), a member of genus Tospovirus in the family Bunyaviridae, infects a large number of leguminosae and solanaceae plants in India. With a view to elucidate the function of nonstructural protein, NSs encoded by the small RNA genome (S RNA), the NSs protein of GBNV- tomato (Karnataka) was over-expressed in E. coli and purified by Ni-NTA chromatography. The purified rNSs protein exhibited an RNA stimulated NTPase activity. Further, this activity was metal ion dependent and was inhibited by adenosine 5' (beta, gamma imido) triphosphate, an ATP analog. The rNSs could also hydrolyze dATP. Interestingly, in addition to the NTPase and dATPase activities, the rNSs exhibited ATP independent 5' RNA/DNA phosphatase activity that was completely inhibited by AMP. The 5' alpha phosphate could be removed from ssDNA, ssRNA, dsDNA and dsRNA thus confirming that rNSs has a novel 5' alpha phosphatase activity. K189A mutation in the Walker motif A (GxxxxGKT) resulted in complete loss of ATPase activity, but the 5' phosphatase activity was unaffected. On the other hand, D159A mutation in the Walker motif B (DExx) resulted in partial loss of both the activities. These results demonstrate for the first time that NSs is a bifunctional enzyme, which could participate in viral movement, replication or in suppression of the host defense mechanism. PMID- 20305787 TI - Medicaid coverage for tobacco dependence treatments in Massachusetts and associated decreases in smoking prevalence. AB - BACKGROUND: Approximately 50% of smokers die prematurely from tobacco-related diseases. In July 2006, the Massachusetts health care reform law mandated tobacco cessation coverage for the Massachusetts Medicaid population. The new benefit included behavioral counseling and all medications approved for tobacco cessation treatment by the U.S. Food and Drug Administration (FDA). Between July 1, 2006 and December 31, 2008, a total of 70,140 unique Massachusetts Medicaid subscribers used the newly available benefit, which is approximately 37% of all Massachusetts Medicaid smokers. Given the high utilization rate, the objective of this study is to determine if smoking prevalence decreased significantly after the initiation of tobacco cessation coverage. METHODS AND FINDINGS: Smoking prevalence was evaluated pre- to post-benefit using 1999 through 2008 data from the Massachusetts Behavioral Risk Factor Survey (BRFSS). The crude smoking rate decreased from 38.3% (95% C.I. 33.6%-42.9%) in the pre-benefit period compared to 28.3% (95% C.I.: 24.0%-32.7%) in the post-benefit period, representing a decline of 26 percent. A demographically adjusted smoking rate showed a similar decrease in the post-benefit period. Trend analyses reflected prevalence decreases that accrued over time. Specifically, a joinpoint analysis of smoking prevalence among Massachusetts Medicaid benefit-eligible members (age 18-64) from 1999 through 2008 found a decreasing trend that was coincident with the implementation of the benefit. Finally, a logistic regression that controlled for demographic factors also showed that the trend in smoking decreased significantly from July 1, 2006 to December 31, 2008. CONCLUSION: These findings suggest that a tobacco cessation benefit that includes coverage for medications and behavioral treatments, has few barriers to access, and involves broad promotion can significantly reduce smoking prevalence. PMID- 20305788 TI - T cell specific adapter protein (TSAd) interacts with Tec kinase ITK to promote CXCL12 induced migration of human and murine T cells. AB - BACKGROUND: The chemokine CXCL12/SDF-1alpha interacts with its G-protein coupled receptor CXCR4 to induce migration of lymphoid and endothelial cells. T cell specific adapter protein (TSAd) has been found to promote migration of Jurkat T cells through interaction with the G protein beta subunit. However, the molecular mechanisms for how TSAd influences cellular migration have not been characterized in detail. PRINCIPAL FINDINGS: We show that TSAd is required for tyrosine phosphorylation of the Lck substrate IL2-inducible T cell kinase (Itk). Presence of Itk Y511 was necessary to boost TSAd's effect on CXCL12 induced migration of Jurkat T cells. In addition, TSAd's ability to promote CXCL12-induced actin polymerization and migration of Jurkat T lymphocytes was dependent on the Itk interaction site in the proline-rich region of TSAd. Furthermore, TSAd-deficient murine thymocytes failed to respond to CXCL12 with increased Itk phosphorylation, and displayed reduced actin polymerization and cell migration responses. CONCLUSION: We propose that TSAd, through its interaction with both Itk and Lck, primes Itk for Lck mediated phosphorylation and thereby regulates CXCL12 induced T cell migration and actin cytoskeleton rearrangements. PMID- 20305789 TI - Dopamine neuron stimulating actions of a GDNF propeptide. AB - BACKGROUND: Neurotrophic factors, such as glial cell line-derived neurotrophic factor (GDNF), have shown great promise for protection and restoration of damaged or dying dopamine neurons in animal models and in some Parkinson's disease (PD) clinical trials. However, the delivery of neurotrophic factors to the brain is difficult due to their large size and poor bio-distribution. In addition, developing more efficacious trophic factors is hampered by the difficulty of synthesis and structural modification. Small molecules with neurotrophic actions that are easy to synthesize and modify to improve bioavailability are needed. METHODS AND FINDINGS: Here we present the neurobiological actions of dopamine neuron stimulating peptide-11 (DNSP-11), an 11-mer peptide from the proGDNF domain. In vitro, DNSP-11 supports the survival of fetal mesencephalic neurons, increasing both the number of surviving cells and neuritic outgrowth. In MN9D cells, DNSP-11 protects against dopaminergic neurotoxin 6-hydroxydopamine (6 OHDA)-induced cell death, significantly decreasing TUNEL-positive cells and levels of caspase-3 activity. In vivo, a single injection of DNSP-11 into the normal adult rat substantia nigra is taken up rapidly into neurons and increases resting levels of dopamine and its metabolites for up to 28 days. Of particular note, DNSP-11 significantly improves apomorphine-induced rotational behavior, and increases dopamine and dopamine metabolite tissue levels in the substantia nigra in a rat model of PD. Unlike GDNF, DNSP-11 was found to block staurosporine- and gramicidin-induced cytotoxicity in nutrient-deprived dopaminergic B65 cells, and its neuroprotective effects included preventing the release of cytochrome c from mitochondria. CONCLUSIONS: Collectively, these data support that DNSP-11 exhibits potent neurotrophic actions analogous to GDNF, making it a viable candidate for a PD therapeutic. However, it likely signals through pathways that do not directly involve the GFRalpha1 receptor. PMID- 20305791 TI - Calculation of disease dynamics in a population of households. AB - Early mathematical representations of infectious disease dynamics assumed a single, large, homogeneously mixing population. Over the past decade there has been growing interest in models consisting of multiple smaller subpopulations (households, workplaces, schools, communities), with the natural assumption of strong homogeneous mixing within each subpopulation, and weaker transmission between subpopulations. Here we consider a model of SIRS (susceptible-infectious recovered-susceptible) infection dynamics in a very large (assumed infinite) population of households, with the simplifying assumption that each household is of the same size (although all methods may be extended to a population with a heterogeneous distribution of household sizes). For this households model we present efficient methods for studying several quantities of epidemiological interest: (i) the threshold for invasion; (ii) the early growth rate; (iii) the household offspring distribution; (iv) the endemic prevalence of infection; and (v) the transient dynamics of the process. We utilize these methods to explore a wide region of parameter space appropriate for human infectious diseases. We then extend these results to consider the effects of more realistic gamma-distributed infectious periods. We discuss how all these results differ from standard homogeneous-mixing models and assess the implications for the invasion, transmission and persistence of infection. The computational efficiency of the methodology presented here will hopefully aid in the parameterisation of structured models and in the evaluation of appropriate responses for future disease outbreaks. PMID- 20305792 TI - Method for Fast CT/SPECT-Based 3D Monte Carlo Absorbed Dose Computations in Internal Emitter Therapy. AB - The DPM (Dose Planning Method) Monte Carlo electron and photon transport program, designed for fast computation of radiation absorbed dose in external beam radiotherapy, has been adapted to the calculation of absorbed dose in patient specific internal emitter therapy. Because both its photon and electron transport mechanics algorithms have been optimized for fast computation in 3D voxelized geometries (in particular, those derived from CT scans), DPM is perfectly suited for performing patient-specific absorbed dose calculations in internal emitter therapy. In the updated version of DPM developed for the current work, the necessary inputs are a patient CT image, a registered SPECT image, and any number of registered masks defining regions of interest. DPM has been benchmarked for internal emitter therapy applications by comparing computed absorption fractions for a variety of organs using a Zubal phantom with reference results from the Medical Internal Radionuclide Dose (MIRD) Committee standards. In addition, the beta decay source algorithm and the photon tracking algorithm of DPM have been further benchmarked by comparison to experimental data. This paper presents a description of the program, the results of the benchmark studies, and some sample computations using patient data from radioimmunotherapy studies using (131)I. PMID- 20305790 TI - Loss of SNAP29 impairs endocytic recycling and cell motility. AB - Intracellular membrane trafficking depends on the ordered formation and consumption of transport intermediates and requires that membranes fuse with each other in a tightly regulated and highly specific manner. Membrane anchored SNAREs assemble into SNARE complexes that bring membranes together to promote fusion. SNAP29 is a ubiquitous synaptosomal-associated SNARE protein. It interacts with several syntaxins and with the EH domain containing protein EHD1. Loss of functional SNAP29 results in CEDNIK syndrome (Cerebral Dysgenesis, Neuropathy, Ichthyosis and Keratoderma). Using fibroblast cell lines derived from CEDNIK patients, we show that SNAP29 mediates endocytic recycling of transferrin and beta1-integrin. Impaired beta1-integrin recycling affected cell motility, as reflected by changes in cell spreading and wound healing. No major changes were detected in exocytosis of VSVG protein from the Golgi apparatus, although the Golgi system acquired a dispersed morphology in SNAP29 deficient cells. Our results emphasize the importance of SNAP29 mediated membrane fusion in endocytic recycling and consequently, in cell motility. PMID- 20305793 TI - Detection of Radiation-Exposure Biomarkers by Differential Mobility Prefiltered Mass Spectrometry (DMS-MS). AB - Technology to enable rapid screening for radiation exposure has been identified as an important need, and, as a part of a NIH / NIAD effort in this direction, metabolomic biomarkers for radiation exposure have been identified in a recent series of papers. To reduce the time necessary to detect and measure these biomarkers, differential mobility spectrometry - mass spectrometry (DMS-MS) systems have been developed and tested. Differential mobility ion filters preselect specific ions and also suppress chemical noise created in typical atmospheric-pressure ionization sources (ESI, MALDI, and others). Differential mobility-based ion selection is based on the field dependence of ion mobility, which, in turn, depends on ion characteristics that include conformation, charge distribution, molecular polarizability, and other properties, and on the transport gas composition which can be modified to enhance resolution. DMS-MS is able to resolve small-molecule biomarkers from nearly-isobaric interferences, and suppresses chemical noise generated in the ion source and in the mass spectrometer, improving selectivity and quantitative accuracy. Our planar DMS design is rapid, operating in a few milliseconds, and analyzes ions before fragmentation. Depending on MS inlet conditions, DMS-selected ions can be dissociated in the MS inlet expansion, before mass analysis, providing a capability similar to MS/MS with simpler instrumentation. This report presents selected DMS-MS experimental results, including resolution of complex test mixtures of isobaric compounds, separation of charge states, separation of isobaric biomarkers (citrate and isocitrate), and separation of nearly-isobaric biomarker anions in direct analysis of a bio-fluid sample from the radiation treated group of a mouse-model study. These uses of DMS combined with moderate resolution MS instrumentation indicate the feasibility of field-deployable instrumentation for biomarker evaluation. PMID- 20305794 TI - Gold(I)-Catalyzed Hydroarylation of Allenes with Indoles. AB - Reaction of a monosubstituted, 1,3-disubstituted, or tetrasubstituted allene with various indoles catalyzed by a 1:1 mixture of a gold(I) N-heterocyclic carbene complex and AgOTf at room temperature leads to hydroarylation with formation of 3 allyl-indoles in modest to good yield. PMID- 20305795 TI - Covalent Adaptable Networks (CANs): A Unique Paradigm in Crosslinked Polymers. AB - Polymer networks possessing reversible covalent crosslinks constitute a novel material class with the capacity for adapting to an externally applied stimulus. These covalent adaptable networks (CANs) represent a trend in polymer network fabrication towards the rational design of structural materials possessing dynamic characteristics for specialty applications. Herein, we discuss the unique attributes of CANs that must be considered when designing, fabricating, and characterizing these smart materials that respond to either thermal or photochemical stimuli. While there are many reversible reactions which to consider as possible crosslink candidates in CANs, there are very few that are readily and repeatedly reversible. Furthermore, characterization of the mechanical properties of CANs requires special consideration owing to their unique attributes. Ultimately, these attributes are what lead to the advantageous properties displayed by CANs, such as recyclability, healability, tunability, shape changes, and low polymerization stress. Throughout this perspective, we identify several trends and future directions in the emerging field of CANs that demonstrate the progress to date as well as the essential elements that are needed for further advancement. PMID- 20305796 TI - Early Marriage in the United States. AB - Despite drastic changes in the American family, a significant minority of Americans marry early. Using data from the National Longitudinal Study of Adolescent Health (N = 14,165), this study evaluates the prevalence and antecedents of early marriage in the United States. The results indicate 25% of women and 16% of men marry before age 23, and early marriage varies widely across a number of characteristics. Individuals who marry earlier are more likely to be from disadvantaged families, from conservative Protestant or Mormon families, to value their religious faith more highly, to have a high-school diploma but a lower educational trajectory, and to cohabit before marriage. Scholars and policymakers interested in marriage should pay adequate attention to understanding and supporting these individuals' marriages. PMID- 20305798 TI - Brief Alcohol Intervention Among At-Risk Drinkers with Diabetes. AB - Twenty-eight patients with diabetes who screened positive for at-risk drinking were assigned to brief alcohol intervention (BAI) (n = 14) or standard care (SC) (n = 14) treatment conditions. All participants completed a baseline interview and one-, three, and six-month follow-up interviews. Across the six-month follow up period, there was a significantly greater reduction in quantity of alcohol consumed in the BAI group. At the six-month follow-up, the BAI group had a greater reduction in quantity of alcohol consumed, percentage of heavy drinking days, and frequency of drinking. Reductions in alcohol use were associated with improved adherence in certain components of diabetes self-care behavior. The results of this study suggest that brief alcohol interventions are efficacious in reducing alcohol use among at-risk drinkers with diabetes and that reductions in alcohol use may result in some improvements in adherence to diabetes self-care behavior. PMID- 20305797 TI - Nutrition and late-life depression: etiological considerations. AB - Depression is a debilitating mental disorder that frequently occurs in older adults, especially in those with vascular diseases. Nutritional factors have the potential to decrease the occurrence of late-life depression but have not been adequately studied. Low folate levels, disturbed omega-3 fatty acid metabolism and obesity have been associated with depression, and may be causal factors. Longitudinal studies are urgently needed in order to examine the potential of dietary factors to prevent late-life depression. PMID- 20305799 TI - Medicinal surface modification of silicon nanowires: impact on calcification and stromal cell proliferation. AB - Medicinal surface modification of silicon nanowires (SiNWs) with selected bisphosphonates, such as the known antiosteoporotic drug alendronate, is described. In terms of specific assays relevant to orthopedic applications, the impact of selected bisphosphonate attachment on acellular calcification in simulated plasma is reported. To further investigate biocompatibility, proliferation assays of these modified nanowires were carried out using an orthopedically relevant cell line: mesenchymal stem cells derived from mouse stroma. It is found that the identity of the bisphosphonate ligand strongly and sensitively impacts its resultant cytotoxicity. PMID- 20305800 TI - Semiparametric regression during 2003-2007. AB - Semiparametric regression is a fusion between parametric regression and nonparametric regression that integrates low-rank penalized splines, mixed model and hierarchical Bayesian methodology - thus allowing more streamlined handling of longitudinal and spatial correlation. We review progress in the field over the five-year period between 2003 and 2007. We find semiparametric regression to be a vibrant field with substantial involvement and activity, continual enhancement and widespread application. PMID- 20305801 TI - Computer-Aided Diagnosis in Mammography Using Content-based Image Retrieval Approaches: Current Status and Future Perspectives. AB - As the rapid advance of digital imaging technologies, the content-based image retrieval (CBIR) has became one of the most vivid research areas in computer vision. In the last several years, developing computer-aided detection and/or diagnosis (CAD) schemes that use CBIR to search for the clinically relevant and visually similar medical images (or regions) depicting suspicious lesions has also been attracting research interest. CBIR-based CAD schemes have potential to provide radiologists with "visual aid" and increase their confidence in accepting CAD-cued results in the decision making. The CAD performance and reliability depends on a number of factors including the optimization of lesion segmentation, feature selection, reference database size, computational efficiency, and relationship between the clinical relevance and visual similarity of the CAD results. By presenting and comparing a number of approaches commonly used in previous studies, this article identifies and discusses the optimal approaches in developing CBIR-based CAD schemes and assessing their performance. Although preliminary studies have suggested that using CBIR-based CAD schemes might improve radiologists' performance and/or increase their confidence in the decision making, this technology is still in the early development stage. Much research work is needed before the CBIR-based CAD schemes can be accepted in the clinical practice. PMID- 20305802 TI - Quantile Regression With Measurement Error. AB - Regression quantiles can be substantially biased when the covariates are measured with error. In this paper we propose a new method that produces consistent linear quantile estimation in the presence of covariate measurement error. The method corrects the measurement error induced bias by constructing joint estimating equations that simultaneously hold for all the quantile levels. An iterative EM type estimation algorithm to obtain the solutions to such joint estimation equations is provided. The finite sample performance of the proposed method is investigated in a simulation study, and compared to the standard regression calibration approach. Finally, we apply our methodology to part of the National Collaborative Perinatal Project growth data, a longitudinal study with an unusual measurement error structure. PMID- 20305803 TI - Drug delivery to the posterior segment of the eye for pharmacologic therapy. AB - Treatment of diseases of the posterior segment of the eye, such as age-related macular degeneration, cytomegalovirus retinitis, diabetic retinopathy, posterior uveitis and retinitis pigmentosa, requires novel drug delivery systems that can overcome the many barriers for efficacious delivery of therapeutic drug concentrations. This challenge has prompted the development of biodegradable and nonbiodegradable sustained-release systems for injection or transplantation into the vitreous as well as drug-loaded nanoparticles, microspheres and liposomes. These drug delivery systems utilize topical, systemic, subconjunctival, intravitreal, transscleral and iontophoretic routes of administration. The focus of research has been the development of methods that will increase the efficacy of spatiotemporal drug application, resulting in more successful therapy for patients with posterior segment diseases. This article summarizes recent advances in the research and development of drug delivery methods of the posterior chamber of the eye, with an emphasis on the use of implantable devices as well as micro- and nanoparticles. PMID- 20305804 TI - Engineering Kinases to Phosphorylate Nucleoside Analogs for Antiviral and Cancer Therapy. AB - Enzyme engineering by directed evolution presents a powerful strategy for tailoring the function and physicochemical properties of biocatalysts to therapeutic and industrial applications. Our laboratory's research focuses on developing novel molecular tools for protein engineering, as well as on utilizing these methods to customize enzymes and to study fundamental aspects of their structure and function. Specifically, we are interested in nucleoside and nucleotide kinases which are responsible for the intracellular phosphorylation of nucleoside analog (NA) prodrugs to their biologically active triphosphates. The high substrate specificity of the cellular kinases often interferes with prodrug activation and consequently lowers the potency of NAs as antiviral and cancer therapeutics. A working solution to the problem is the co-adminstration of a promiscuous kinase from viruses, bacteria, and other mammals. However, further therapeutic enhancements of NAs depend on the selective and efficient prodrug phosphorylation. In the absence of true NA kinases in nature, we are pursuing laboratory evolution strategies to generate efficient phosphoryl-transfer catalysts. This review summarizes some of our recent work in the field and outlines future challenges. PMID- 20305807 TI - Retraction: The bicarbonate transporter is essential for Bacillus anthracis lethality. PMID- 20305805 TI - Too old to fight? Aging and its toll on innate immunity. AB - Elderly individuals display increased susceptibility to chronic inflammatory diseases and microbial infections, such as periodontitis and oral aspiration pneumonia. The resurgent interest in innate immunity in the 2000s has been accompanied by parallel studies to understand the impact of aging on the function of the innate immune system, which not only provides first-line defense but is essential for the development of adaptive immunity. This review summarizes and discusses our current understanding of age-associated molecular alterations in neutrophils and macrophages, key inflammatory phagocytes implicated in both protective and destructive host responses. The analysis of recent literature suggests that, in advanced age, phagocytes undergo significant changes in signal transduction pathways that may affect their ability to perform antimicrobial functions or regulate the inflammatory response. These abnormalities are expected to contribute to the pathology of oral infection-driven inflammatory diseases in the elderly. Moreover, the elucidation of age-associated defects in the innate immune system will facilitate the development of intervention therapeutic strategies to promote or restore innate immune function and improve the quality of health in old age. PMID- 20305808 TI - Benthic composition of a healthy subtropical reef: baseline species-level cover, with an emphasis on algae, in the Northwestern Hawaiian Islands. AB - The Northwestern Hawaiian Islands (NWHI) are considered to be among the most pristine coral reef ecosystems remaining on the planet. These reefs naturally contain a high percent cover of algal functional groups with relatively low coral abundance and exhibit thriving fish communities dominated by top predators. Despite their highly protected status, these reefs are at risk from both direct and indirect anthropogenic sources. This study provides the first comprehensive data on percent coverage of algae, coral, and non-coral invertebrates at the species level, and investigates spatial diversity patterns across the archipelago to document benthic communities before further environmental changes occur in response to global warming and ocean acidification. Monitoring studies show that non-calcified macroalgae cover a greater percentage of substrate than corals on many high latitude reef sites. Forereef habitats in atoll systems often contain high abundances of the green macroalga Microdictyon setchellianum and the brown macroalga Lobophora variegata, yet these organisms were uncommon in forereefs of non-atoll systems. Species of the brown macroalgal genera Padina, Sargassum, and Stypopodium and the red macroalgal genus Laurencia became increasingly common in the two northernmost atolls of the island chain but were uncommon components of more southerly islands. Conversely, the scleractinian coral Porites lobata was common on forereefs at southern islands but less common at northern islands. Currently accepted paradigms of what constitutes a "healthy" reef may not apply to the subtropical NWHI, and metrics used to gauge reef health (e.g., high coral cover) need to be reevaluated. PMID- 20305809 TI - Modelling the species distribution of flat-headed cats (Prionailurus planiceps), an endangered South-East Asian small felid. AB - BACKGROUND: The flat-headed cat (Prionailurus planiceps) is one of the world's least known, highly threatened felids with a distribution restricted to tropical lowland rainforests in Peninsular Thailand/Malaysia, Borneo and Sumatra. Throughout its geographic range large-scale anthropogenic transformation processes, including the pollution of fresh-water river systems and landscape fragmentation, raise concerns regarding its conservation status. Despite an increasing number of camera-trapping field surveys for carnivores in South-East Asia during the past two decades, few of these studies recorded the flat-headed cat. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we designed a predictive species distribution model using the Maximum Entropy (MaxEnt) algorithm to reassess the potential current distribution and conservation status of the flat headed cat. Eighty-eight independent species occurrence records were gathered from field surveys, literature records, and museum collections. These current and historical records were analysed in relation to bioclimatic variables (WorldClim), altitude (SRTM) and minimum distance to larger water resources (Digital Chart of the World). Distance to water was identified as the key predictor for the occurrence of flat-headed cats (>50% explanation). In addition, we used different land cover maps (GLC2000, GlobCover and SarVision LLC for Borneo), information on protected areas and regional human population density data to extract suitable habitats from the potential distribution predicted by the MaxEnt model. Between 54% and 68% of suitable habitat has already been converted to unsuitable land cover types (e.g. croplands, plantations), and only between 10% and 20% of suitable land cover is categorised as fully protected according to the IUCN criteria. The remaining habitats are highly fragmented and only a few larger forest patches remain. CONCLUSION/SIGNIFICANCE: Based on our findings, we recommend that future conservation efforts for the flat-headed cat should focus on the identified remaining key localities and be implemented through a continuous dialogue between local stakeholders, conservationists and scientists to ensure its long-term survival. The flat-headed cat can serve as a flagship species for the protection of several other endangered species associated with the threatened tropical lowland forests and surface fresh-water sources in this region. PMID- 20305810 TI - Assessing the performance capabilities of LRE-based assays for absolute quantitative real-time PCR. AB - BACKGROUND: Linear regression of efficiency or LRE introduced a new paradigm for conducting absolute quantification, which does not require standard curves, can generate absolute accuracies of +/-25% and has single molecule sensitivity. Derived from adapting the classic Boltzmann sigmoidal function to PCR, target quantity is calculated directly from the fluorescence readings within the central region of an amplification profile, generating 4-8 determinations from each amplification reaction. FINDINGS: Based on generating a linear representation of PCR amplification, the highly visual nature of LRE analysis is illustrated by varying reaction volume and amplification efficiency, which also demonstrates how LRE can be used to model PCR. Examining the dynamic range of LRE further demonstrates that quantitative accuracy can be maintained down to a single target molecule, and that target quantification below ten molecules conforms to that predicted by Poisson distribution. Essential to the universality of optical calibration, the fluorescence intensity generated by SYBR Green I (FU/bp) is shown to be independent of GC content and amplicon size, further verifying that absolute scale can be established using a single quantitative standard. Two high performance lambda amplicons are also introduced that in addition to producing highly precise optical calibrations, can be used as benchmarks for performance testing. The utility of limiting dilution assay for conducting platform independent absolute quantification is also discussed, along with the utility of defining assay performance in terms of absolute accuracy. CONCLUSIONS: Founded on the ability to exploit lambda gDNA as a universal quantitative standard, LRE provides the ability to conduct absolute quantification using few resources beyond those needed for sample preparation and amplification. Combined with the quantitative and quality control capabilities of LRE, this kinetic-based approach has the potential to fundamentally transform how real-time qPCR is conducted. PMID- 20305812 TI - Generous leaders and selfish underdogs: pro-sociality in despotic macaques. AB - Actively granting food to a companion is called pro-social behavior and is considered to be part of altruism. Recent findings show that some non-human primates behave pro-socially. However, pro-social behavior is not expected in despotic species, since the steep dominance hierarchy will hamper pro-sociality. We show that some despotic long-tailed macaques do grant others access to food. Moreover, their dominance hierarchy determines pro-social behavior in an unexpected way: high-ranking individuals grant, while low-ranking individuals withhold their partner access to food. Surprisingly, pro-social behavior is not used by subordinates to obtain benefits from dominants, but by dominants to emphasize their dominance position. Hence, Machiavellian macaques rule not through "fear above love", but through "be feared when needed and loved when possible". PMID- 20305811 TI - Epimorphin regulates bile duct formation via effects on mitosis orientation in rat liver epithelial stem-like cells. AB - Understanding how hepatic precursor cells can generate differentiated bile ducts is crucial for studies on epithelial morphogenesis and for development of cell therapies for hepatobiliary diseases. Epimorphin (EPM) is a key morphogen for duct morphogenesis in various epithelial organs. The role of EPM in bile duct formation (DF) from hepatic precursor cells, however, is not known. To address this issue, we used WB-F344 rat epithelial stem-like cells as model for bile duct formation. A micropattern and a uniaxial static stretch device was used to investigate the effects of EPM and stress fiber bundles on the mitosis orientation (MO) of WB cells. Immunohistochemistry of liver tissue sections demonstrated high EPM expression around bile ducts in vivo. In vitro, recombinant EPM selectively induced DF through upregulation of CK19 expression and suppression of HNF3alpha and HNF6, with no effects on other hepatocytic genes investigated. Our data provide evidence that EPM guides MO of WB-F344 cells via effects on stress fiber bundles and focal adhesion assembly, as supported by blockade EPM, beta1 integrin, and F-actin assembly. These blockers can also inhibit EPM-induced DF. These results demonstrate a new biophysical action of EPM in bile duct formation, during which determination of MO plays a crucial role. PMID- 20305813 TI - Subinhibitory concentrations of thymol reduce enterotoxins A and B and alpha hemolysin production in Staphylococcus aureus isolates. AB - BACKGROUND: Targeting bacterial virulence factors is now gaining interest as an alternative strategy to develop new types of anti-infective agents. It has been shown that thymol, when used at low concentrations, can inhibit the TSST-1 secretion in Staphylococcus aureus. However, there are no data on the effect of thymol on the production of other exotoxins (e.g., alpha-hemolysin and enterotoxins) by S. aureus. METHODOLOGY/PRINCIPAL FINDINGS: Secretion of alpha hemolysin, SEA and SEB in both methicillin-sensitive and methicillin-resistant S. aureus isolates cultured with graded subinhibitory concentrations of thymol was detected by immunoblot analysis. Hemolysin and tumor necrosis factor (TNF) release assays were performed to elucidate the biological relevance of changes in alpha-hemolysin, SEA and SEB secretion induced by thymol. In addition, the influence of thymol on the transcription of hla, sea, and seb (the genes encoding alpha-hemolysin, SEA and SEB, respectively) was analyzed by quantitative RT-PCR. Thymol inhibited transcription of hla, sea and seb in S. aureus, resulting in a reduction of alpha-hemolysin, SEA and SEB secretion and, thus, a reduction in hemolytic and TNF-inducing activities. CONCLUSIONS/SIGNIFICANCE: Subinhibitory concentrations of thymol decreased the production of alpha-hemolysin, SEA and SEB in both MSSA and MRSA in a dose-dependent manner. These data suggest that thymol may be useful for the treatment of S. aureus infections when used in combination with beta-lactams and glycopeptide antibiotics, which induce expression of alpha hemolysin and enterotoxins at subinhibitory concentrations. Furthermore, the structure of thymol may potentially be used as a basic structure for development of drugs aimed against these bacterial virulence factors. PMID- 20305814 TI - Identification of a deubiquitinating enzyme as a novel AGS3-interacting protein. AB - Activator of G protein Signaling 3 (AGS3) is a receptor-independent G protein activator that has been implicated in multiple biological events such as brain development, neuroplasticity and addiction, cardiac function, Golgi structure/function, macroautophagy and metabolism. However, how AGS3 is regulated is little known. We demonstrate here that AGS3 interacts with a ubiquitin specific protease USP9x, and this interaction is at least partially mediated through the C-terminal G protein regulatory domain of AGS3. Knockdown of USP9x causes a moderate reduction in the level of AGS3. In contrast, overexpression of either USP9x or its deubiquitinating domain UCH increases the amount of AGS3, whereas expression of the mutant UCH domain that lacks deubiquitinating activity does not have the same effect. As previously observed in AGS3 knockdown cells, the localization of several marker proteins of the late Golgi compartments is disturbed in cells depleted of USP9x. Taken together, our study suggests that USP9x can modulate the level of a subpopulation of AGS3, and this modulation plays a role in regulating the structure of the late Golgi compartments. Finally, we have found that levels of AGS3 and USP9x are co-regulated in the prefrontal cortex of rats withdrawn from repeated cocaine treatment. In conjunction with the above data, this observation indicates a potential role of USP9X in the regulation of the AGS3 level during cocaine-induced neuroplasticity. PMID- 20305815 TI - Cyclic and acyclic defensins inhibit human immunodeficiency virus type-1 replication by different mechanisms. AB - Defensins are antimicrobial peptides expressed by plants and animals. In mammals there are three subfamilies of defensins, distinguished by structural features: alpha, beta and theta. Alpha and beta-defensins are linear peptides with broad anti-microbial activity that are expressed by many mammals including humans. In contrast, theta-defensins are cyclic anti-microbial peptides made by several non human primates but not humans. All three defensin types have anti-HIV-1 activity, but their mechanisms of action differ. We studied the anti-HIV-1 activity of one defensin from each group, HNP-1 (alpha), HBD-2 (beta) and RTD-1 (theta). We examined how each defensin affected HIV-1 infection and demonstrated that the cyclic defensin RTD-1 inhibited HIV-1 entry, while acyclic HNP-1 and HBD-2 inhibited HIV-1 replication even when added 12 hours post-infection and blocked viral replication after HIV-1 cDNA formation. We further found that all three defensins downmodulated CXCR4. Moreover, RTD-1 inactivated X4 HIV-1, while HNP-1 and HBD-2 inactivated both X4 and R5 HIV-1. The data presented here show that acyclic and cyclic defensins block HIV-1 replication by shared and diverse mechanisms. Moreover, we found that HNP-1 and RTD-1 directly inhibited firefly luciferase enzymatic activity, which may affect the interpretation of previously published data. PMID- 20305816 TI - BORIS (CTCFL) is not expressed in most human breast cell lines and high grade breast carcinomas. AB - BORIS (CTCFL) is the only known paralog of the versatile regulatory protein CTCF, a multifunctional DNA binding protein that mediates distinct gene regulatory functions involved in cell growth, differentiation, and apoptosis. Unlike CTCF, the expression of BORIS is normally restricted to specific cells in testes (the only cells where CTCF is not expressed), where it may play a role in reprogramming the methylation pattern of male germ line DNA. Frequent amplification of the 20q13.2 region, which contains the BORIS gene, and expression of BORIS transcripts in diverse human tumors and cell lines have led to the hypothesis that aberrant expression of BORIS may play a role in tumorigenesis by interfering with CTCF functions. However, recent studies using more quantitative methods indicate low frequency of BORIS expression in melanoma, ovarian, prostate, and bladder carcinomas. To investigate the relationship between chromosome 20q13 amplification and BORIS mRNA levels within breast cancer cell lines and tissues, we developed a quantitative RT-PCR assay to measure the levels of BORIS mRNA. Endpoint RT-PCR assays were also used to investigate the possible expression of alternatively spliced variants. Using multiple primer sets and controls, we found that neither mature BORIS transcripts nor spliced variants are commonly expressed at detectable levels in malignant breast cells or tissues, although endogenous BORIS transcripts can be induced in MCF-7 cells following 5 aza-2'-deoxycytidine treatment. In conclusion, in most breast cancer cells, endogenous BORIS is unlikely to be expressed at sufficient levels to interfere with CTCF functions. Thus it is improbable that aberrant BORIS expression plays a role in most human breast cancers. PMID- 20305817 TI - Progression of the "Psychological Typhoon Eye" and variations since the Wenchuan earthquake. AB - BACKGROUND: In 2008 after a massive earthquake jolted Wenchuan, China, we reported an effect that we termed a "Psychological Typhoon Eye": the closer to the center of the devastated area, the lower the level of concern felt by residents about safety and health. We now report on the progression of this effect and the development of new variations after the quake as well as investigating potential explanations. METHODOLOGY/PRINCIPAL FINDINGS: We conducted two sequential surveys of 5,216 residents in non-devastated and devastated areas in September-October 2008 and April-May 2009. Respondents were asked five questions to assess their concerns about safety and health. A MANCOVA showed a significant inverse effect of residential devastation level on the estimated number of medical and psychological workers needed, the estimated probability of an epidemic outbreak, and the estimated number of self-protective behaviors needed (Ps<0.001), in spite of the passage of one year. The level of post-earthquake concern decreased significantly with an increase in the residential devastation level. Additionally, we observed two variations in the "Psychological Typhoon Eye" effect, in that the respondents' concern decreased with increasing relational distance between a respondent and victims who had suffered either physical or economic damage. CONCLUSIONS/SIGNIFICANCE: The previously reported effect of a "Psychological Typhoon Eye" remains robust over a 1-year period. We found that the "psychological immunization" theory did not provide a satisfactory explanation for these intriguing results. Our findings may be useful in understanding how people become resilient to threats. PMID- 20305818 TI - Honeybee associative learning performance and metabolic stress resilience are positively associated. AB - BACKGROUND: Social-environmental influences can affect animal cognition and health. Also, human socio-economic status is a covariate factor connecting psychometric test-performance (a measure of cognitive ability), educational achievement, lifetime health, and survival. The complimentary hypothesis, that mechanisms in physiology can explain some covariance between the same traits, is disputed. Possible mechanisms involve metabolic biology affecting integrity and stability of physiological systems during development and ageing. Knowledge of these relationships is incomplete, and underlying processes are challenging to reveal in people. Model animals, however, can provide insights into connections between metabolic biology and physiological stability that may aid efforts to reduce human health and longevity disparities. RESULTS: We document a positive correlation between a measure of associative learning performance and the metabolic stress resilience of honeybees. This relationship is independent of social factors, and may provide basic insights into how central nervous system (CNS) function and metabolic biology can be associated. Controlling for social environment, age, and learning motivation in each bee, we establish that learning in Pavlovian conditioning to an odour is positively correlated with individual survival time in hyperoxia. Hyperoxia induces oxidative metabolic damage, and provides a measure of metabolic stress resistance that is often related to overall lifespan in laboratory animals. The positive relationship between Pavlovian learning ability and stress resilience in the bee is not equally established in other model organisms so far, and contrasts with a genetic cost of improved associative learning found in Drosophila melanogaster. CONCLUSIONS: Similarities in the performances of different animals need not reflect common functional principles. A correlation of honeybee Pavlovian learning and metabolic stress resilience, thereby, is not evidence of a shared biology that will give insight about systems integrity in people. Yet, the means to resolve difficult research questions often come from findings in distant areas of science while the model systems that turn out to be valuable are sometimes the least predictable. Our results add to recent findings indicating that honeybees can become instrumental to understanding how metabolic biology influences life outcomes. PMID- 20305819 TI - Cancer cell expression of autotaxin controls bone metastasis formation in mouse through lysophosphatidic acid-dependent activation of osteoclasts. AB - BACKGROUND: Bone metastases are highly frequent complications of breast cancers. Current bone metastasis treatments using powerful anti-resorptive agents are only palliative indicating that factors independent of bone resorption control bone metastasis progression. Autotaxin (ATX/NPP2) is a secreted protein with both oncogenic and pro-metastatic properties. Through its lysosphospholipase D (lysoPLD) activity, ATX controls the level of lysophosphatidic acid (LPA) in the blood. Platelet-derived LPA promotes the progression of osteolytic bone metastases of breast cancer cells. We asked whether ATX was involved in the bone metastasis process. We characterized the role of ATX in osteolytic bone metastasis formation by using genetically modified breast cancer cells exploited on different osteolytic bone metastasis mouse models. METHODOLOGY/PRINCIPAL FINDINGS: Intravenous injection of human breast cancer MDA-B02 cells with forced expression of ATX (MDA-B02/ATX) to immunodeficiency BALB/C nude mice enhanced osteolytic bone metastasis formation, as judged by increased bone loss, tumor burden, and a higher number of active osteoclasts at the metastatic site. Mouse breast cancer 4T1 cells induced the formation of osteolytic bone metastases after intracardiac injection in immunocompetent BALB/C mice. These cells expressed active ATX and silencing ATX expression inhibited the extent of osteolytic bone lesions and decreased the number of active osteoclasts at the bone metastatic site. In vitro, osteoclast differentiation was enhanced in presence of MDA B02/ATX cell conditioned media or recombinant autotaxin that was blocked by the autotaxin inhibitor vpc8a202. In vitro, addition of LPA to active charcoal treated serum restored the capacity of the serum to support RANK-L/MCSF-induced osteoclastogenesis. CONCLUSION/SIGNIFICANCE: Expression of autotaxin by cancer cells controls osteolytic bone metastasis formation. This work demonstrates a new role for LPA as a factor that stimulates directly cancer growth and metastasis, and osteoclast differentiation. Therefore, targeting the autotaxin/LPA track emerges as a potential new therapeutic approach to improve the outcome of patients with bone metastases. PMID- 20305820 TI - How is sentence processing affected by external semantic and syntactic information? Evidence from event-related potentials. AB - BACKGROUND: A crucial question for understanding sentence comprehension is the openness of syntactic and semantic processes for other sources of information. Using event-related potentials in a dual task paradigm, we had previously found that sentence processing takes into consideration task relevant sentence-external semantic but not syntactic information. In that study, internal and external information both varied within the same linguistic domain-either semantic or syntactic. Here we investigated whether across-domain sentence-external information would impact within-sentence processing. METHODOLOGY: In one condition, adjectives within visually presented sentences of the structure [Det] [Noun]-[Adjective]-[Verb] were semantically correct or incorrect. Simultaneously with the noun, auditory adjectives were presented that morphosyntactically matched or mismatched the visual adjectives with respect to gender. FINDINGS: As expected, semantic violations within the sentence elicited N400 and P600 components in the ERP. However, these components were not modulated by syntactic matching of the sentence-external auditory adjective. In a second condition, syntactic within-sentence correctness-variations were combined with semantic matching variations between the auditory and the visual adjective. Here, syntactic within-sentence violations elicited a LAN and a P600 that did not interact with semantic matching of the auditory adjective. However, semantic mismatching of the latter elicited a frontocentral positivity, presumably related to an increase in discourse level complexity. CONCLUSION: The current findings underscore the open versus algorithmic nature of semantic and syntactic processing, respectively, during sentence comprehension. PMID- 20305821 TI - Discovery of fragment molecules that bind the human peroxiredoxin 5 active site. AB - The search for protein ligands is a crucial step in the inhibitor design process. Fragment screening represents an interesting method to rapidly find lead molecules, as it enables the exploration of a larger portion of the chemical space with a smaller number of compounds as compared to screening based on drug sized molecules. Moreover, fragment screening usually leads to hit molecules that form few but optimal interactions with the target, thus displaying high ligand efficiencies. Here we report the screening of a homemade library composed of 200 highly diverse fragments against the human Peroxiredoxin 5 protein. Peroxiredoxins compose a family of peroxidases that share the ability to reduce peroxides through a conserved cysteine. The three-dimensional structures of these enzymes ubiquitously found throughout evolution have been extensively studied, however, their biological functions are still not well understood and to date few inhibitors have been discovered against these enzymes. Six fragments from the library were shown to bind to the Peroxiredoxin 5 active site and ligand-induced chemical shift changes were used to drive the docking of these small molecules into the protein structure. The orientation of the fragments in the binding pocket was confirmed by the study of fragment homologues, highlighting the role of hydroxyl functions that hang the ligands to the Peroxiredoxin 5 protein. Among the hit fragments, the small catechol molecule was shown to significantly inhibit Peroxiredoxin 5 activity in a thioredoxin peroxidase assay. This study reports novel data about the ligand-Peroxiredoxin interactions that will help considerably the development of potential Peroxiredoxin inhibitors. PMID- 20305822 TI - Bridgehead effect in the worldwide invasion of the biocontrol harlequin ladybird. AB - Recent studies of the routes of worldwide introductions of alien organisms suggest that many widespread invasions could have stemmed not from the native range, but from a particularly successful invasive population, which serves as the source of colonists for remote new territories. We call here this phenomenon the invasive bridgehead effect. Evaluating the likelihood of such a scenario is heuristically challenging. We solved this problem by using approximate Bayesian computation methods to quantitatively compare complex invasion scenarios based on the analysis of population genetics (microsatellite variation) and historical (first observation dates) data. We applied this approach to the Harlequin ladybird Harmonia axyridis (HA), a coccinellid native to Asia that was repeatedly introduced as a biocontrol agent without becoming established for decades. We show that the recent burst of worldwide invasions of HA followed a bridgehead scenario, in which an invasive population in eastern North America acted as the source of the colonists that invaded the European, South American and African continents, with some admixture with a biocontrol strain in Europe. This demonstration of a mechanism of invasion via a bridgehead has important implications both for invasion theory (i.e., a single evolutionary shift in the bridgehead population versus multiple changes in case of introduced populations becoming invasive independently) and for ongoing efforts to manage invasions by alien organisms (i.e., heightened vigilance against invasive bridgeheads). PMID- 20305823 TI - Cardiac deletion of Smyd2 is dispensable for mouse heart development. AB - Chromatin modifying enzymes play a critical role in cardiac differentiation. Previously, it has been shown that the targeted deletion of the histone methyltransferase, Smyd1, the founding member of the SET and MYND domain containing (Smyd) family, interferes with cardiomyocyte maturation and proper formation of the right heart ventricle. The highly related paralogue, Smyd2 is a histone 3 lysine 4- and lysine 36-specific methyltransferase expressed in heart and brain. Here, we report that Smyd2 is differentially expressed during cardiac development with highest expression in the neonatal heart. To elucidate the functional role of Smyd2 in the heart, we generated conditional knockout (cKO) mice harboring a cardiomyocyte-specific deletion of Smyd2 and performed histological, functional and molecular analyses. Unexpectedly, cardiac deletion of Smyd2 was dispensable for proper morphological and functional development of the murine heart and had no effect on global histone 3 lysine 4 or 36 methylation. However, we provide evidence for a potential role of Smyd2 in the transcriptional regulation of genes associated with translation and reveal that Smyd2, similar to Smyd3, interacts with RNA Polymerase II as well as to the RNA helicase, HELZ. PMID- 20305824 TI - First qualification study of serum biomarkers as indicators of total body burden of osteoarthritis. AB - BACKGROUND: Osteoarthritis (OA) is a debilitating chronic multijoint disease of global proportions. OA presence and severity is usually documented by x-ray imaging but whole body imaging is impractical due to radiation exposure, time and cost. Systemic (serum or urine) biomarkers offer a potential alternative method of quantifying total body burden of disease but no OA-related biomarker has ever been stringently qualified to determine the feasibility of this approach. The goal of this study was to evaluate the ability of three OA-related biomarkers to predict various forms or subspecies of OA and total body burden of disease. METHODOLOGY/PRINCIPAL FINDINGS: Female participants (461) with clinical hand OA underwent radiography of hands, hips, knees and lumbar spine; x-rays were comprehensively scored for OA features of osteophyte and joint space narrowing. Three OA-related biomarkers, serum hyaluronan (sHA), cartilage oligomeric matrix protein (sCOMP), and urinary C-telopeptide of type II collagen (uCTX2), were measured by ELISA. sHA, sCOMP and uCTX2 correlated positively with total osteophyte burden in models accounting for demographics (age, weight, height): R(2) = 0.60, R(2) = 0.47, R(2) = 0.51 (all p<10(-6)); sCOMP correlated negatively with total joint space narrowing burden: R(2) = 0.69 (p<10(-6)). Biomarkers and demographics predicted 35-38% of variance in total burden of OA (total joint space narrowing or osteophyte). Joint size did not determine the contribution to the systemic biomarker concentration. Biomarker correlation with disease in the lumbar spine resembled that in the rest of the skeleton. CONCLUSIONS/SIGNIFICANCE: We have suspected that the correlation of systemic biomarkers with disease has been hampered by the inability to fully phenotype the burden of OA in a patient. These results confirm the hypothesis, revealed upon adequate patient phenotyping, that systemic joint tissue concentrations of several biomarkers can be quantitative indicators of specific subspecies of OA and of total body burden of disease. PMID- 20305825 TI - Hepatocellular carcinoma displays distinct DNA methylation signatures with potential as clinical predictors. AB - BACKGROUND: Hepatocellular carcinoma (HCC) is characterized by late detection and fast progression, and it is believed that epigenetic disruption may be the cause of its molecular and clinicopathological heterogeneity. A better understanding of the global deregulation of methylation states and how they correlate with disease progression will aid in the design of strategies for earlier detection and better therapeutic decisions. METHODS AND FINDINGS: We characterized the changes in promoter methylation in a series of 30 HCC tumors and their respective surrounding tissue and identified methylation signatures associated with major risk factors and clinical correlates. A wide panel of cancer-related gene promoters was analyzed using Illumina bead array technology, and CpG sites were then selected according to their ability to classify clinicopathological parameters. An independent series of HCC tumors and matched surrounding tissue was used for validation of the signatures. We were able to develop and validate a signature of methylation in HCC. This signature distinguished HCC from surrounding tissue and from other tumor types, and was independent of risk factors. However, aberrant methylation of an independent subset of promoters was associated with tumor progression and etiological risk factors (HBV or HCV infection and alcohol consumption). Interestingly, distinct methylation of an independent panel of gene promoters was strongly correlated with survival after cancer therapy. CONCLUSION: Our study shows that HCC tumors exhibit specific DNA methylation signatures associated with major risk factors and tumor progression stage, with potential clinical applications in diagnosis and prognosis. PMID- 20305827 TI - Stimuli-responsive mechanically adaptive polymer nanocomposites. AB - A new series of biomimetic stimuli-responsive nanocomposites, which change their mechanical properties upon exposure to physiological conditions, was prepared and investigated. The materials were produced by introducing percolating networks of cellulose nanofibers or "whiskers" derived from tunicates into poly(vinyl acetate) (PVAc), poly(butyl methacrylate) (PBMA), and blends of these polymers, with the objective of determining how the hydrophobicity and glass-transition temperature (Tg) of the polymer matrix affect the water-induced mechanically dynamic behavior. Below the Tg (approximately 60-70 degrees C), the incorporation of whiskers (15.1-16.5% v/v) modestly increased the tensile storage moduli (E') of the neat polymers from 0.6 to 3.8 GPa (PBMA) and from 2 to 5.2 GPa (PVAc). The reinforcement was much more dramatic above Tg, where E' increased from 1.2 to 690 MPa (PVAc) and approximately 1 MPa to 1.1 GPa (PBMA). Upon exposure to physiological conditions (immersion in artificial cerebrospinal fluid, ACSF, at 37 degrees C) all materials displayed a decrease in E'. The most significant contrast was seen in PVAc; for example, the E' of a 16.5% v/v PVAc/whisker nanocomposite decreased from 5.2 GPa to 12.7 MPa. Only a modest modulus decrease was measured for PBMA/whisker nanocomposite; here the E' of a 15.1% v/v PBMA/whisker nanocomposite decreased from 3.8 to 1.2 GPa. A systematic investigation revealed that the magnitude of the mechanical contrast was related to the degree of swelling with ACSF, which was shown to increase with whisker content, temperature, and polarity of the matrix (PVAc>PBMA). The mechanical morphing of the new materials can be described in the framework of both the percolation and Halpin-Kardos models for nanocomposite reinforcement, and is the result of changing interactions among the nanoparticles and plasticization of the matrix upon swelling. PMID- 20305826 TI - Role of infection in the development and exacerbation of asthma. AB - Respiratory infections are associated with wheezing illnesses in all ages and may also impact the development and severity of asthma. Respiratory tract infections caused by viruses, Chlamydophila or Mycoplasma have been hypothesized to have significant roles in the pathogenesis of asthma. Progress is being made toward establishing the mechanisms by which these agents can cause acute wheezing and impact the pathophysiology of asthma. Host factors probably contribute to the risk of asthma inception and exacerbation, and these contributions may also vary with respect to early- versus adult-onset disease. This review discusses these various associations as they pertain to the development and exacerbation of asthma. PMID- 20305828 TI - Myeloid Malignancies and the Marrow Microenvironment: Some Recent Studies in Patients with MDS. AB - There is growing evidence for a role of the hemopoietic microenvironment in the pathophysiology of myelodysplastic syndromes (MDS). Effects of various cytokines on the marrow microenvironment of patients with MDS have been studied. Autoimmunity, i.e. a reaction of autologous T lymphocytes against components of the marrow is also operative in a proportion of patients with MDS. The negative feed-back loop that controls tumor necrosis factor (TNF)alpha levels in healthy individuals is apparently disrupted in MDS due to auto-amplification signals involving TNFalpha and interleukin (IL-32). IL-32 mRNA levels in primary adherent cells from patients with MDS are 14- to 17-fold higher than in controls. In contrast, cells from patients with chronic myelomonocytic leukemia (CMML), a myeloproliferative disorder with low TNFalpha levels, express IL-32 at only 1/10 the level observed in controls. Damage in the microenvironment may occur secondary to oxidative stress, which may also lead to accelerated shortening of telomeres. This is, indeed, true for hematopoietic cells in MDS marrow, but telomere length in marrow stroma does not differ from that in age-matched healthy individuals. Nevertheless, the stroma shows functional aberrancies. Stroma derived signals facilitate apoptosis in clonal hematopoietic cells but not in normal CD34+ cells. Thus while stroma dysfunction is likely due to signals derived from the hematopoietic clone rather than being intrinsic, it does affect clonal death or survival, respectively. Therefore, signals exchanged between both compartments could serve as targets for therapeutic interventions. PMID- 20305829 TI - Prevalence and Timing of Diagnosable Mental Health, Alcohol, and Substance Use Problems among Older Adolescents in the Child Welfare System. AB - This study reports the prevalence of PTSD, major depression, alcohol abuse/dependence and substance abuse/dependence diagnoses assessed with a structured clinical interview protocol in a population-based, multi-state, age cohort of older adolescents about to exit child welfare systems. PTSD was the most common diagnosis and was observed at rates above those seen in the general population. Rates of specific diagnoses varied according to gender, race, type of child welfare placement, and state of residence. In general, African American youth and those in kinship family foster care were less likely to have mental health and substance use problems. Analysis of the timing of onset relative to entry into care revealed that Caucasian youth were more likely to have diagnoses prior to entry into state custody, and race differentials were less pronounced for diagnosis after placement in foster care. Observed state-to-state differences suggest that age of entry into care and the likelihood of pre-existing mental health and substance use conditions could be attributable to child welfare policies regarding screening and placement. PMID- 20305830 TI - Synthesis and structure assignment of the minor metabolite arising from the frog pathogen Mycobacterium liflandii. AB - Total synthesis and structure assignment of the minor metabolite present in lipid extracts of the frog pathogen Mycobacterium liflandii are reported. PMID- 20305831 TI - Integration Grid Errors for Meta-GGA-Predicted Reaction Energies: Origin of Grid Errors for the M06 Suite of Functionals. AB - We have assessed integration grid errors arising from the use of popular DFT quadrature schemes for a set of 34 organic reaction energies. The focus is primarily on M05-2X and the M06 suite of functionals (M06-L, M06, M06-2X, and M06 HF). M05-2X, M06, and M06-2X outperform popular older DFT functionals for the reaction energies studied, and offer accuracies comparable to results from perturbative hybrid DFT functionals. However, these new functionals are more sensitive to the choice of quadrature grid than previous generations of DFT functionals. Errors in predicted reaction energies arising from the use of the popular SG-1 grid, which is the default in the Q-Chem package, are significant. In particular, M06-HF reaction energies computed with the SG-1 grid exhibit errors ranging from -6.7 to 3.2 kcal mol(-1) relative to results computed with a very fine integration grid. This grid-sensitivity is not a problem for meta-GGA functionals in general, but is instead due to the specific functional forms used in these functionals. The large grid errors are traced to the kinetic energy density enhancement factor utilized in the exchange component of the M05-2X and M06 functionals. This term contains empirically adjusted parameters that are of large magnitude for all of the M06 functionals and for M06-HF in particular. The product of these large constants with modest integration errors for the kinetic energy density results in very large errors in individual contributions to the exchange energy. This gives rise to the troubling large errors exhibited by these functionals for certain integration grids. PMID- 20305832 TI - Synthesis and Solid State Structure of Fluorous Probe Molecules for Fluorous Separation Applications. AB - A series of colored hydrocarbon and fluorocarbon tagged 1-fluoro-4-alkylamino anthraquinones and 1,4-bis-alkylamino-anthraquinone probe molecules were synthesized from a (fluorinated) alkyl amine and 1,4-difluoroanthraquinone to aid in the development of fluorous separation applications. The anthraquinones displayed stacking of the anthraquinone tricycle and interdigitation of the (fluorinated) alkyl chains in the solid state. Furthermore, intramolecular N H...O hydrogen bonds forced the hydrocarbon and fluorocarbon tags into a conformation pointing away from the anthraquinone tricycle, with the angle of the tricycle plane normal and the main (fluorinated) alkyl vector ranging from 1 to 39 degrees . Separation of the probe molecules on fluorous silica gel showed that the degree of fluorination of the probe molecules plays only a minor role with most eluents (e.g., hexane-ethyl acetate and methyl nonafluorobutyl ethers-ethyl acetate). However, toluene as eluent caused a pronounced separation by degree of fluorination for fluorocarbon, but not hydrocarbon tagged probe molecules on both silica gel and fluorous silica gel. These studies suggest that hydrocarbon and fluorocarbon tagged anthraquinones are useful probe molecules for the development of laboratory scale fluorous separation applications. PMID- 20305833 TI - HITECH-The Carrot and the stick: What every orthopedic surgeon needs to know. PMID- 20305834 TI - Bearing surfaces in hip arthroplasty. PMID- 20305835 TI - A simple method for fashioning an antibiotic cement-coated interlocking intramedullary nail. AB - Acute or chronic infection in the presence of nonunited fracture or chronic nonunion often necessitates staged surgical treatment. Treatment typically involves removal of hardware, debridement of infected tissue, use of local antibiotic delivery, and a long-term course of intravenous antibiotics. Several methods of local antibiotic delivery using antibiotic-impregnated polymethylmethacrylate (PMMA) have been commonly used, including commercial or hand-fashioned PMMA beads, antibiotic spacers, and antibiotic PMMA-coated guide rods. While these methods address the problem of infection, they do little to address fracture stability. In this report we describe a simple method for fashioning an antibiotic cement-coated interlocking intramedullary nail to treat an infected tibia fracture. This technique capitalizes on local delivery of antibiotics through use of antibiotic cement with the added benefit of improving fracture stability and fixation with an interlocking nail to achieve bony union. PMID- 20305836 TI - Distal humerus osteotomy for supracondylar fracture malunion in children: a study of perioperative complications. AB - Previous studies have found a wide range of perioperative complications associated with distal humerus osteotomies for malunion of supracondylar fractures in children. Our hypothesis was that the surgery would have few perioperative complications when performed at a pediatric center. We examined perioperative complications of corrective osteotomy for malunited supracondylar humerus fractures in 41 patients treated at Children's Hospital Los Angeles between 1987 and 2002, and we established the risk factors associated with these complications. The overall complication rate was 32% (13/41). In the early surgeries, performed between 1987 and 1997, the complication rate was 53% (10/19); 6 (32%) of the 19 patients required reoperation. In the later surgeries performed during 1998 and 2002, the complication rate was 14% (3/22); no patient required reoperation. The complication rate was significantly lower (P = .0005) when lateral-entry pins were used to fix the osteotomy (13% [2/15]) than when other fixation methods were used (42% [11/26]). Using current techniques and performing the surgery in a pediatric center, we report a 0% reoperation rate and a 14% complication rate in distal humerus osteotomies for surgeries performed after 1997, a rate that we believe is acceptable. Furthermore, there are fewer complications of the surgery when lateral-entry pins are used to fix the osteotomy compared with other fixation methods. PMID- 20305837 TI - Labral support shelf arthroplasty for the early stages of severe Legg-Calve Perthes disease. AB - The best treatment for Legg-Calve-Perthes disease remains unknown, and various methods of treatment have been shown to yield conflicting results. Treatment with a labral support shelf arthroplasty is ideal when an increased arc of the acetabulum is needed to contain an enlarged femoral head, when extension of the lateral border of the acetabulum is needed to prevent hinge subluxation, and when a larger surface area is needed for remodeling. Twenty patients with unilateral Catterall classes III and IV and lateral pillar groups B and C disease in the necrotic or fragmentation stage were treated with a shelf arthroplasty. Eleven hips demonstrated hinge subluxation. Success was defined as achievement of a round or oval femoral head, and failure was defined as a flat femoral head. Clinical examination evaluated the presence of pain, limp, and range of motion. Eighteen of the 20 hips (90%) had a successful result. Hinge subluxation was eliminated in all 11 hips. All 18 patients with a successful result had no pain, no limp, and a functional range of motion. The 2 hips considered a failure were in the oldest patients. Treatment with a labral support shelf arthroplasty fostered femoral head sphericity and prevented incongruence in hips otherwise at risk for poor results. Ninety percent of hips had a round or oval femoral head with no pain, no limp, and a functional range of motion. PMID- 20305838 TI - Chondromyxoid fibroma of the radial shaft treated with nonvascularized fibular autograft. AB - Chondromyxoid fibroma is a benign yet highly recurrent neoplasm of bone, usually found in the metaphyseal segments of long bones. We present the case of an unusual diaphyseal chondromyxoid fibroma of the radius and review the literature regarding these rare chondroid neoplasms. PMID- 20305839 TI - Painless, atraumatic, isolated lateral compartment syndrome of the leg: an unusual triad of atypical findings. AB - Compartment syndrome can be a devastating complication with significant morbidity when not recognized or treated expediently. Among the classic pentad of signs and symptoms associated with compartment syndrome, pain that is out of proportion to the injury is often cited as the earliest and most sensitive. We present a case report of an atypical presentation of compartment syndrome of the leg in which a patient taking lithium for bipolar disorder did not report pain out of proportion to the injury mechanism. Lithium has been implicated in altering pain perception and increasing the tolerance and threshold for pain, but this has not been widely reported in the orthopedic literature. In addition to compartment syndrome that was painless, the patient presented with 2 additional atypical findings. She presented with compartment syndrome that was atraumatic and isolated to only 1 out of the 4 compartments of the leg. A compartment syndrome that is painless, atraumatic, and isolated to a single compartment represents an unusual triad of atypical findings that has not been previously reported. With unusual presentations of compartment syndrome, there is an increased risk of late or unrecognized diagnosis, consequently increasing the likelihood of significant nerve damage or muscle necrosis. Clinicians have historically applied a higher level of scrutiny to patients who were deemed "obtunded," that is, those in whom an assessment of pain cannot be reliably determined. In the past, obtunded patients have included intubated or comatose patients, infants and children, mentally disabled patients, and patients with altered mental status, nerve injury, or distracting injuries. Based on evidence from the psychiatry and anesthesia literatures, we propose that patients taking lithium should be added to this list of "obtunded" patients in whom a reliable assessment of pain may not be possible. PMID- 20305840 TI - Arthroscopic excision of a painful bipartite patella fragment. AB - Bipartite patella is an uncommon finding, with the majority of cases discovered incidentally on radiographs. Occasionally, bipartite patella can become painful through sports activities, overuse, or following an injury, and the large majority of these cases resolve with nonoperative treatment. However, for patients who do not respond to a prolonged course of nonoperative treatment, surgical options may be considered. We report a successful case of arthroscopic excision of a painful bipartite patella fragment in a 19-year-old male collegiate basketball player. A review of the literature is included. PMID- 20305841 TI - Septic trochanteric bursitis in an adolescent. AB - Trochanteric bursitis, whether septic or inflammatory in origin, is a condition that affects middle-aged patients. Here we report the rare case of an adolescent with septic trochanteric bursitis (treated successfully with intravenous antibiotics), review the available literature on septic bursitis, illustrate the importance of prompt recognition and treatment of this condition in any age group, and describe the clinical presentation and the radiologic findings. PMID- 20305842 TI - Fibula stress fracture mimicking a malignancy. AB - Stress fractures may be easily misdiagnosed as another entity, especially tumors, which may prompt very severe surgical treatment and sometimes amputation. The appropriate use of modern radiography may make the difference in proper diagnosis of stress fractures. PMID- 20305843 TI - Pulmonary embolism after knee arthroscopy. AB - Symptomatic deep venous thrombosis (DVT) after knee arthroscopy is a rare occurrence, especially in the ambulatory patient. In this report, we present an unusual case of pulmonary emboli in a young, active patient after arthroscopic treatment of an osteochondral defect via microfracture technique. We also review the current literature and recommendations for prophylaxis against postarthroscopic DVT. In our review, we found that DVT prophylaxis appears to effectively decrease nonsymptomatic DVT formation after knee arthroscopy. However, the relatively low rate of symptomatic DVT does not yet seem to warrant the associated risks of pharmaceutical prophylaxis. Further trials may provide more insight. PMID- 20305844 TI - Mandibular implant overdentures followed for over 10 years: patient compliance and prosthetic maintenance. AB - PURPOSE: The mandibular implant overdenture is a popular treatment modality and is well documented in the literature. Follow-up studies with a long observation period are difficult to perform due to the increasing age of patients. The present data summarize a long-term clinical observation of patients with implant overdentures. MATERIALS AND METHODS: Between 1984 and 1997, edentulous patients were consecutively admitted for treatment with an implant overdenture. The dentures were connected to the implants by means of bars or ball anchors. Regular maintenance was provided with at least one or two scheduled visits per year. Recall attendance and reasons for dropout were analyzed based on the specific history of the patient. Denture maintenance service, relining, repair, and fabrication of new dentures were identified, and complications with the retention devices specified separately. RESULTS: In the time period from 1984 to 2008, 147 patients with a total of 314 implants had completed a follow-up period of >10 years. One hundred one patients were still available in 2008, while 46 patients were not reexamined for various reasons. Compliance was high, with a regular recall attendance of >90%. More than 80% of dentures remained in continuous service. Although major prosthetic maintenance was rather low in relation to the long observation period, visits to a dental hygienist and dentist resulted in an annual visit rate of 1.5 and 2.4, respectively. If new dentures became necessary, these were made in student courses, which increased the treatment time and number of appointments needed. Complications with the retention devices consisted mostly of the mounting of new female retainers, the repair of bars, and the changing of ball anchors. The average number of events and the rate of prosthetic service with ball anchors were significantly higher than those with bars. Twenty-two patients changed from ball anchors to bars; 9 patients switched from a clip bar to a rigid U-shaped bar. CONCLUSIONS: This long-term follow-up study demonstrates that implant overdentures are a favorable solution for edentulous patients with regular maintenance. In spite of specific circumstances in an aging population, it is possible to provide long-term care, resulting in a good prognosis and low risk for this treatment modality. For various reasons the dropout rate can be considerable in elderly patients and prosthetic service must be provided regularly. PMID- 20305845 TI - A treatment planning classification for oligodontia. AB - PURPOSE: The aim of this research was to provide a classification for patients with oligodontia that could act as an aid in treatment planning. MATERIALS AND METHODS: Panoramic radiograph records of 70 patients with oligodontia were used to categorize the extent of the disability and treatment modality. Patients were classified into types 1 through 3 depending on the number of missing primary and permanent teeth, as well as in relation to their prosthodontic requirements. The radiographs were then assessed independently on two separate occasions by three experienced clinicians to validate the classification. RESULTS: There was a high level of intrarater consistency in allocating patients into the three different types with a Kappa (k) score of 0.77 for clinician 1, 0.87 for clinician 2, and 0.94 for clinician 3. There was also a strong interrater agreement (overall k score: 0.88). A k score greater then 0.6 is regarded as being good and greater than 0.8 as being very good. CONCLUSIONS: Oligodontia is a heterogeneous condition. Patients with oligodontia can be classified as having three different types according to the extent of their disability and the complexity of their prosthodontic requirements. This classification is a reliable diagnostic tool based on the positive outcome of the inter- and intrarater consistency. PMID- 20305846 TI - Restoring severely compromised anterior teeth with zirconia crowns and feather edged margin preparations: a 3-year follow-up of a prospective clinical trial. AB - This prospective clinical trial sought to evaluate the 3-year clinical results of anterior teeth restored with 0.3-mm-thick zirconia copings and feather-edged marginal preparations. Ten patients received 19 single-tooth restorations in the anterior maxilla to restore severely decayed teeth. After a mean observation period of 39.2 months, no material fracture occurred and all crowns had acceptable surfaces. A survival and success rate of 100% was recorded, which suggests that the clinical method may be a reliable treatment modality for restoring severely compromised anterior teeth. PMID- 20305847 TI - Randomized controlled trial investigating the effect of an acrylic-based resilient liner on perceived chewing ability in edentulous patients wearing mandibular complete dentures. AB - PURPOSE: The aim of this study was to investigate the effect of an acrylic-based resilient liner (ARL) on perceived chewing ability in patients using mandibular complete dentures compared with that of patients using mandibular complete dentures with a conventional acrylic resin (CAR). MATERIALS AND METHODS: This randomized controlled trial was conducted at two centers from April 2004 to July 2006. Seventy-four subjects were randomly allocated to either the ARL or CAR group using a random permuted block method after obtaining written informed consent. A valid questionnaire listing 35 foods was used to evaluate the subjects' perceived chewing ability of each item, assessed according to the following scale: 0=cannot eat, 1=can eat with difficulty, and 2=can eat easily. If subjects did not eat the food because they disliked it or had not eaten it since first wearing dentures, they filled in a triangle or square, respectively. These figures were treated as a 0 during analysis. RESULTS: No significant differences were observed between the ARL and CAR groups. The perceived chewing ability of subjects with new complete dentures was significantly higher than that of those with their old complete dentures. The duration of edentulism was positively associated with perceived chewing ability. CONCLUSIONS: An ARL applied to mandibular complete dentures has no significant impact on the perceived chewing ability of edentulous patients in comparison to a CAR. PMID- 20305848 TI - Marginal bone loss with mandibular two-implant overdentures using different loading protocols: a systematic literature review. AB - PURPOSE: Mandibular two-implant overdentures opposing conventional complete maxillary dentures have been proposed as the standard for complete denture service. Monitoring marginal bone loss around implants is regarded as the most important criterion in determining the success of implants. The aim of this systematic literature review was to critically evaluate the literature on short- and long-term marginal bone loss associated with mandibular two-implant overdentures using different loading protocols. MATERIALS AND METHODS: The MEDLINE, EMBASE, and PubMed (using medical subject headings) databases were searched using the restriction of articles in English only. Other articles were identified from the reference lists of the articles found, as well as from early online articles. Reviewed studies were those on two oral implants supporting mandibular overdentures with different loading protocols. Marginal bone loss was evaluated as well as the validity of using marginal bone loss measurements for determining the success of implants. RESULTS: Twenty-five studies met the review criteria. Clinical studies involving conventional loading showed long-term results; however, early and immediate loading protocols were only in the short term. High success or survival rates of two implants supporting mandibular overdentures were reported, regardless of the loading protocol. A lack of standardization was revealed in the radiographic methods used for measuring marginal bone loss and the success criteria on which results were based. Long term outcomes of the effect of different loading protocols on marginal bone loss were not found. Due to the wide methodologic variation among the included studies, it was difficult to compare data between studies or to determine long term marginal bone loss patterns with this treatment. For conventional two-stage and one-stage loading protocols, the range of marginal bone loss seen in the first year was 0.2 to 0.7 mm and 0.0 to 2.0 mm, respectively. For early loading protocols, the range was 0.0 to 0.2 mm; immediate loading protocols saw a marginal bone loss of around 0.7 mm in the first year. CONCLUSIONS: Short-term findings indicate that so far, there is no detrimental effect on marginal bone levels with early and immediate loading protocols. However, to recommend these protocols in the long-term for two implants supporting mandibular overdentures may be premature. PMID- 20305849 TI - The association of chewing ability and diet in elderly complete denture patients. AB - The purpose of this study was to investigate the relationship between chewing ability and diet among elderly edentulous patients whose dentures were funded by the Department of Health in Kaohsiung City, Taiwan. A cluster sample of 103 elderly edentulous subjects 65 years and older (68 men, 35 women) was gathered randomly and assessed through use of a questionnaire. The responses to queries regarding demographics, health, and chewing capabilities were correlated with dietary guidelines for the five basic food groups. Chi-square test analysis revealed that subjects with chewing difficulty consumed fewer vegetables. Only 17% of the total subject pool consumed the recommended daily allowance (RDA) of vegetables. Approximately 58% of subjects reported dissatisfaction with their dentures and 51% reported discomfort on chewing. Approximately 4% of the subjects met the RDA standards for all five food groups and 4% did not meet the RDA standards for any of the five food groups. Patient satisfaction with the comfort of their denture during mastication significantly impacted the diet of these elderly edentulous patients. PMID- 20305850 TI - Fracture rates of IPS Empress all-ceramic crowns--a systematic review. AB - PURPOSE: The aim of this study was to evaluate the clinical fracture rate of crowns fabricated with the pressable, leucite-reinforced ceramic IPS Empress, and relate the results to the type of tooth restored. MATERIALS AND METHODS: The database SCOPUS was searched for clinical studies involving full-coverage crowns made of IPS Empress. To assess the fracture rate of the crowns in relation to the type of restored tooth and study, Poisson regression analysis was used. RESULTS: Seven clinical studies were identified involving 1,487 adhesively luted crowns (mean observation time: 4.5+/-1.7 years) and 81 crowns cemented with zinc phosphate cement (mean observation time: 1.6+/-0.8 years). Fifty-seven of the adhesively luted crowns fractured (3.8%). The majority of fractures (62%) occurred between the third and sixth year after placement. There was no significant influence regarding the test center on fracture rate, but the restored tooth type played a significant role. The hazard rate (per year) for crowns was estimated to be 5 in every 1,000 crowns for incisors, 7 in every 1,000 crowns for premolars, 12 in every 1,000 crowns for canines, and 16 in every 1,000 crowns for molars. One molar crown in the zinc-phosphate group fractured after 1.2 years. CONCLUSION: Adhesively luted IPS Empress crowns showed a low fracture rate for incisors and premolars and a somewhat higher rate for molars and canines. The sample size of the conventionally luted crowns was too small and the observation period too short to draw meaningful conclusions. PMID- 20305851 TI - Survival of Dicor glass-ceramic dental restorations over 20 years: Part IV. The effects of combinations of variables. AB - PURPOSE: Previous studies have shown the relationship of individual clinical variables to the survival of Dicor (Corning Glass Works) restorations. The purpose of the present investigation was to examine the effect of combinations of these variables on the intraoral survival of Dicor restorations. MATERIALS AND METHODS: Dicor glass-ceramic restorations (n=1,444) were placed in 417 adult patients. Failure was defined as a restoration that required remake because of material fracture. The survival of restorations with different combinations of variables that were each individually associated with survival was described using Kaplan-Meier survivor functions. The statistical significance of differences in survival between different combinations of specific predictor variables was examined using the proportional hazards model. RESULTS: Kaplan Meier survival analysis indicated that significantly worse survival rates were found for restorations that included combinations of molar teeth, a dentin core, and a glass-ionomer luting agent; molar teeth, a dentin core, and a resin luting agent; and single-rooted teeth, a dentin core, and a glass-ionomer luting agent than for any other combinations tested. The Cox proportional hazards model described a hazard ratio of 3.37 (95% confidence interval [CI]: 2.23 to 5.08) for molar teeth (versus single-rooted teeth), 2.65 (95% CI: 1.44 to 4.87) for dentin core (versus gold core), 2.35 (95% CI: 1.58 to 3.51) for men (versus women), and 1.72 (95% CI: 1.13 to 2.60) for glass-ionomer luting agent (versus resin) after adjusting for the other variables in the model. CONCLUSION: Factors beyond individual restoration design impact the survival of Dicor glass-ceramic. These include sex, tooth position, and restorations luted to gold core foundation bases. PMID- 20305852 TI - Prospective evaluation of zirconia posterior fixed partial dentures: four-year clinical results. AB - PURPOSE: In this prospective clinical study, the performance of three- and four unit fixed partial dentures (FPDs) with frameworks fabricated of yttria partially stabilized zirconia was determined after a mean observation period of 50 months. The study focused on the survival of the restoration (in situ criterion) and the success of the ceramic veneers (no defect). MATERIALS AND METHODS: Seventy-five patients with a maximum of two missing teeth and an antagonistic dentition were treated at the Department of Prosthodontics, University of Goettigen, with 99 posterior FPDs. Fifty-one specimens (experimental group) were veneered with an experimental ceramic suitable for titanium and zirconia frameworks (thermal expansion coefficient [TEC]: 8.5 microm/m*K); 48 restorations (Ceram-S group) were veneered with a commercially available low-fusing ceramic optimized for zirconia frameworks (TEC: 9.5 microm/m*K). All restorations were luted with zinc phosphate cement. Statistical analysis was performed according to the Kaplan Meier method; time-dependent success rates of the different types of ceramic veneers were analyzed using the log-rank test. RESULTS: Seven restorations were lost: 4 due to technical complications and 3 due to biologic complications. The overall survival rate after 48 months was 94% (Kaplan-Meier analysis). Twenty three events required clinical intervention for restoration maintenance: 13 ceramic veneer chippings (polishing), 6 losses of retention (recementation), 3 caries lesions (filling therapy), and 1 loss of vitality (endodontic treatment). Between the two groups of veneering materials, no significant difference in the probability for success was determined (log-rank test, P=.81). CONCLUSIONS: Within a mean observation period of 4 years, sufficient survival rates for zirconia-based posterior FPDs could be verified. The main complications included fracture of the ceramic veneering material and decementation, which occurred mainly in the mandible. PMID- 20305853 TI - Evaluation of color duplication in metal-ceramic complexes using visual and instrumental shade-matching systems. AB - This study was designed to evaluate color differences (DE) between intended and fabricated shades of various metal-ceramic complexes using visual and instrumental shade determination. Forty-two master disks were made to represent every tab in two shade guides. The shades of the master disks were determined visually and instrumentally. Accordingly, 84 experimental disks were fabricated. Color measurements of the master and fabricated disks were performed using a spectrophotometer. Visual shade determination showed a significantly lower DE value than the instrumental shade determination. However, all groups showed DE values exceeding 2.75, which could be considered perceivable and therefore clinically unacceptable. A reliable shade duplication of an existing metal ceramic restoration cannot be ensured, regardless of the method of shade assessment. PMID- 20305854 TI - A modified method for rebasing implant-retained overdentures. AB - There is a constant need for rebasing implant-retained overdentures because of the inevitable continuous absorption of the underlying residual ridge, which results in a lack of proper occlusion and possible rotation of the denture around the retentive components. This step-by-step article describes all of the clinical and laboratory procedures needed for rebasing a mandibular implant overdenture retained with a bar on two implants, securing an accurate fit. This procedure can be applied successfully for rebasing overdentures with different superstructures (ball attachments or magnets), and for replacing worn or damaged retentive components and matrices. PMID- 20305855 TI - Adhesive-mediated enhancement of occlusal force measurements in patients with existing and new complete dentures: a pilot study. AB - A disposable gnathometer was used to compare measurements of incisal and premolar occlusal forces in removable prosthesis-wearing patients with and without the use of a denture adhesive. Twenty-four patients with maxillary complete dentures opposed by complete or partial mandibular dentures were tested. Denture adhesive significantly improved incisal and premolar occlusal force for the maxillary complete dentures, as well as incisal occlusal force for both existing and new dentures. The occlusal force in patients with mandibular removable partial dentures exceeded that with mandibular complete dentures. Denture adhesive appears to be beneficial for both existing and new dentures, with existing dentures exhibiting an increased benefit relative to newer dentures. PMID- 20305856 TI - Candida albicans and denture stomatitis: evaluation of its presence in the lesion, prosthesis, and blood. AB - Denture stomatitis is a primarily oral disease that affects denture wearers. The presence of Candida albicans in the palatal mucosa, on the internal surface of the maxillary denture, and in the blood of patients with denture stomatitis was evaluated. Although the results did not show C albicans in the bloodstream of patients, a strong relationship between denture stomatitis and Candida sp was confirmed for both the palatal mucosa and maxillary denture. PMID- 20305857 TI - Attachment systems for mandibular single-implant overdentures: an in vitro retention force investigation on different designs. AB - PURPOSE: The aim of this study was to investigate the retentive force of six different attachment systems used for mandibular single-implant overdentures, including two prototype large ball attachment designs. MATERIALS AND METHODS: Two prototype ball attachments of larger dimensions (7.9 and 5.9 mm) and four commercially available ball and stud attachments of standard dimensions (2.25 and 4.0 mm) were evaluated on three identical test casts resembling an edentulous mandible with severe residual ridge resorption. Five samples from each attachment system (n=30) were connected to three different implants (8.0-mm wide diameter, 3.75-mm regular diameter, and 4.0-mm regular diameter). An Instron testing machine with a computer software package was used to deliver a vertical dislodging force at a cross-head speed of 50 mm/min to each overdenture sample from the anterior direction. A total of 300 pull tests were conducted (50 per attachment system). The maximum load (retentive force) required to separate each overdenture from the supporting implant was then measured. RESULTS: The highest retentive force (36.97+/-2.23 N) was achieved with the 7.9-mm prototype ball attachment design, followed in a decreasing order by the 5.9-mm prototype ball attachment design (32.06+/-2.59 N), the standard 2.25-mm ball attachment (17.32+/ 3.68 N), Locator white (12.39+/-0.55 N), Locator pink (9.40 N+/-0.74 N), and Locator blue (3.83+/-0.64 N). A statistically significant difference (P<.0001) was found between all attachments. CONCLUSIONS: Attachment systems of larger dimensions provided higher retentive forces for mandibular single-implant overdentures. Further in vitro and in vivo research is necessary to determine prosthodontic outcomes with these attachments in edentulous patients prior to their routine clinical use internationally. PMID- 20305858 TI - A histologic investigation of direct pulp capping in rodents with dentin adhesives and calcium hydroxide. AB - OBJECTIVE: To investigate reactions of pulp tissue when in contact with the dentin adhesives Resulcin AquaPrime + MonoBond (RAPMB, Merz Dental), Scotchbond 1 (SB1, 3M ESPE), and Gluma Comfort Bond (GCB, Heraeus Kulzer) in comparison with calcium hydroxide after 1 to 70 days. METHOD AND MATERIALS: An occlusal cavity was prepared in 152 molars of 76 Wistar rats. The pulps were exposed and dentin adhesives placed on the pulp tissue of 10 molars for each dentin adhesive group and time period. Eight molars per time period served as controls and were capped with calcium hydroxide. All cavities were restored with composite resin. The animals were sacrificed 1, 3, 7, and 70 days after pulp capping. Pulp tissue was histologically evaluated for the following criteria: bacterial infection, inflammatory cells, necrosis, and reparative dentin. The data were statistically evaluated using the Kruskal-Wallis test (P < .05). RESULTS: Overall, significantly more bacterial infections were detected 1, 3, 7, and 70 days after pulp capping with dentin adhesive (P < .05). In all dentin adhesive groups, 1 day after direct pulp capping, significantly more inflammatory cells were found, whereas after 7 days, this was only the case for the SB1 group (P < .05). After 70 days, capping with calcium hydroxide resulted in significantly less necrosis than with RAPMB and SB1 (P < .05). Regarding necrosis, SB1 showed the worst results: Pulp necrosis occurred significantly more often than with calcium hydroxide and GCB (P < .05). After the application of calcium hydroxide, significantly more reparative dentin formation occurred (P < .05). CONCLUSION: Direct pulp capping with calcium hydroxide seems to produce remarkably better results than with dentin adhesive. PMID- 20305859 TI - Cavernous sinus thrombosis in a patient with facial myiasis. AB - Cavernous sinus thrombosis is a severe encephalic complication of the cervicofacial infections that can lead to death if not treated in adequate time. Among the several etiologies related to the development of this infection, myiasis has not been reported, enforcing the importance of the report of a case of thrombosis of the cavernous sinus developed from a facial myiasis. PMID- 20305860 TI - Thurston syndrome: oral and systemic manifestations. Case report and review of the literature. AB - Orofaciodigital (OFD) syndrome is a generic name for a variety of different but possibly related genetic disorders that result in malformations of the mouth, teeth, jaw, facial bones, hands, and feet and are therefore categorized as oroacral disorders. Nine subtypes of OFD syndromes have been identified. OFD type V is known as Thurston syndrome, of which only 11 cases have been reported to date. A case is reported of a 19-year-old man with this syndrome. A brief review of previously reported cases and discussion of anomalies of the syndrome is presented. PMID- 20305861 TI - Clinical evaluation of a fixed (retrievable) implant-supported prosthesis in the edentulous jaw: a 5-year report. AB - OBJECTIVE: This retrospective study evaluated the success rate of a fixed retrievable prosthesis based on an electroforming technique combining the advantages of screw- and cement-retained principles. METHOD AND MATERIALS: Forty patients (17 men and 23 women) with a mean age of 62.2 years were treated. A total of 353 implants were placed in the edentulous maxilla, mandible, or both jaws to allow prosthetic rehabilitations with 55 fixed prostheses. Clinical success of the implants was based on the criteria of Buser. Technical complications monitored throughout the wearing period are described. Retrievability of the restoration with a conventional crown remover was checked at 6, 12, and 36 months. The cumulative survival rate of the implants was measured. RESULTS: After a mean observation period of 4.08 years (range 22 to 62 months), a cumulative survival rate of 99.15% was recorded for the 234 maxillary implants (234 Camlog RootLine, Camlog) and for the 119 mandibular implants (72 Camlog RootLine, 47 Camlog ScrewLine). Three implants failed before prosthetic loading. Monitored technical complications were seen in 10.91% of the restorations; they comprised ceramic chip-off and relining. CONCLUSIONS: This fixed implant-retained prosthesis based on electroforming indicates a comparable clinical efficacy to other techniques and allows scheduled retrieval. PMID- 20305862 TI - Immediate loading of full-arch fixed prostheses supported by axial and tilted implants for the treatment of edentulous atrophic mandibles. AB - OBJECTIVES: This study aimed to evaluate the long-term prognosis of immediately loaded fixed full prostheses for the treatment of edentulous patients with extreme bone atrophy in the posterior mandibular region. MATERIAL AND METHODS: Twenty-four edentulous patients with atrophic posterior mandibles were treated by means of a complete prosthesis sustained by both axial and tilted fixtures. The insertion of tilted implants was carefully planned by means of computed tomography scan analysis and measuring width and height of residual bone. Implant type, length, and diameter were chosen, as well as implant angulation, according to the All-on-Four protocol and avoiding the course of the mandibular nerve. The prosthesis was delivered no later than 2 days after implant surgery. Implant survival and prosthesis success were assessed clinically and radiographically up to 42 months of follow-up. Measurement of peri-implant bone loss was based on periapical radiographs after 12 months of loading. RESULTS: All implants survived and all prostheses were successful at the time of this study reporting. The mean follow-up was 30.1 months with a range of 14 to 44 months. The average peri implant bone loss was 0.85 mm after 12 months (0.8 mm for tilted implants and 0.9 mm for axial implants). No significant difference in marginal bone loss was observed between axial and tilted implants. CONCLUSIONS: The immediate rehabilitation of patients with extreme atrophic mandibles can be successful with careful planning and particular attention during the surgical placement of the implants, as shown by the excellent outcomes of the present study. PMID- 20305863 TI - Dystrophic calcifications arising in the masseter muscle: a case report. AB - Calcium salt deposits in the presence of normal calcium/phosphorus metabolism involving tissues that do not physiologically calcify are referred to as dystrophic calcification. The condition may be associated with a variety of systemic disorders. Additionally, injured tissue of any kind is predisposed to dystrophic calcification. The case of a 21-year-old man with two isolated dystrophic calcifications in the right masseter muscle is presented. Dystrophic calcifications should be studied carefully and differentiated from lesions resulting from other syndromes that manifest calcification of soft tissues. The lack of a classification system of soft tissue calcifications complicates the management and study of the condition. PMID- 20305864 TI - Three cases of subpontic osseous hyperplasia of the mandible: a report. AB - Subpontic osseous hyperplasia is a relatively uncommon benign submucosal mass of normal bone found beneath a pontic. Three cases of mandibular subpontic osseous hyperplasia are described, adding to the 40 existing cases in the English language literature. Subpontic osseous hyperplasia may represent a unique reactive osseous metaplasia in the subpontic region, with chronic stimuli and functional or occlusal stress as possible etiologies. This article aims to address the clinical significance, treatment considerations, and radiographic correlation of subpontic osseous hyperplasia. PMID- 20305865 TI - Short-term effects of systemic antibiotics during periodontal healing. AB - OBJECTIVES: To investigate the short-term effects of nonsurgical therapy (scaling and root planing, SRP) on the subgingival microbiota in chronic (CP) and aggressive (AP) periodontal disease. METHOD AND MATERIALS: Ninety-seven CP and AP subjects underwent full-mouth SRP on 2 consecutive days. AP patients were randomly assigned to either receive systemic metronidazole plus amoxicillin (AP+AB) or were treated mechanically alone (AP). Pathogens were identified with 16S rRNA oligodeoxynucleotide probes and dot-blot hybridization before and at days 2, 3, 4, 7, 10, and 21 of healing. CP subjects were treated by scaling and root planing along with placebo tablets. RESULTS: Initially, AP cell counts were 69.9- (Porphyromonas gingivalis), 10.2- (Aggregatibacter actinomycetemcomitans), 5.7- (Tannerella forsythia), and 3.3-fold (Prevotella intermedia) enhanced compared to CP cell counts. Following SRP, immediate elimination occurred in single individuals of all three treatment groups at day 2. After SRP plus antibiotic therapy (AP+AB), the prevalence scores dropped beyond the levels of AP and CP, beginning at day 7, and remained low until day 21 (P =or< .05). Clinical healing statistically benefited from SRP with no differences among the three treatment groups. CONCLUSION: Nonsurgical therapy resulted in both a suppression and early elimination of single taxa immediately after completion of active treatment. Systemic antibiotics significantly accelerate the suppression of the periodontal microflora, but have limited effect on the elimination of target isolates during healing. PMID- 20305866 TI - Novel ceria-stabilized tetragonal zirconia/alumina nanocomposite as framework material for posterior fixed dental prostheses: preliminary results of a prospective case series at 1 year of function. AB - OBJECTIVE: To examine the clinical performance of veneered ceria-stabilized tetragonal zirconia/alumina-nanocomposite (Ce-TZP/A-nanocomposite) frameworks for three-unit fixed dental prostheses (FDPs). METHOD AND MATERIALS: Eight patients in need of one FDP replacing one premolar or molar were included in this case series. Eight Ce-TZP/A-nanocomposite FDP frameworks were fabricated with a CAD/CAM system (Hint-Els) and veneered with a zirconia veneering ceramic (Vintage ZR, Shofu). The FDPs were cemented with resin cement (baseline) and were evaluated at baseline; 2 weeks; and 3, 6, and 12 months after cementation. For the technical evaluation, the USPHS criteria were used. The biologic outcome was judged by comparing the plaque control record (PCR), bleeding on probing (BOP), and probing pocket depth (PPD) of the abutment teeth (test) and untreated contralateral teeth (control). Radiographs were made at baseline and at 6 and 12 months of follow-up. The data were descriptively analyzed. RESULTS: The mean observation period of the eight examined FDPs was 12.8 +/- 1.1 months. The survival rate of the FDPs was 100%. Furthermore, no technical or biologic complications were found. No differences of the mean (m) PCR (test: 0.1 +/- 0.1, control: 0.2 +/- 0.2), mBOP (test: 0.2 +/- 0.2, control: 0.1 +/- 0.1), and mPPD (test: 2.6 +/- 0.8, control: 2.6 +/- 0.6) were found between test and control teeth. CONCLUSIONS: Ce-TZP/A nanocomposite was found to be a reliable framework material at 1 year of function. Longer observation periods and randomized controlled clinical trials including more patients are needed to validate these findings. PMID- 20305867 TI - Etiologic factors of hyposalivation and consequences for oral health. AB - Hyposalivation is represented by a reduced salivary flow rate and can be caused by etiologic factors such as systemic diseases and intake of various medications or by radiotherapy following head and neck cancer. The aim of this review was to compile data about the qualitative and quantitative changes of salivary components during hyposalivation, and to summarize their consequences for oral health. A Medline/PubMed/Scopus search was conducted to identify and summarize articles published in English and German that reported on etiology of hyposalivation and changes in the salivary composition due to hyposalivation of different origins. The search revealed 94 articles, 71 of which were original articles. Apart from the reduction of the salivary flow rate, the quality of saliva is strongly altered because of systemic diseases, medications, and radiotherapy, including increased viscosity and pH shift to more acidic values and changes in salivary protein compositions. Furthermore, hyposalivation may be accompanied by pronounced shifts in specific microbial components, in particular toward a highly acidogenic microflora. Moreover, therapy of hyposalivation is often restricted to palliative treatment (ie, saliva substitutes or gels). To prevent tooth tissue demineralization, clinicians should consider saliva substitutes that are supersaturated with calcium and phosphates and contain fluoride. PMID- 20305868 TI - Bacterial leakage of provisional restorative materials used in endodontics. AB - OBJECTIVE: To test the bacterial sealing ability of commonly used provisional endodontic restorative materials. METHOD AND MATERIALS: This study investigated Cavit (3M ESPE), Ketac (3M ESPE), DuoTemp (Coltane/Whaledent), and a combination technique using Ketac and Cavit. One hundred molars were randomly selected and then mounted in an apparatus that isolated the crown portion of the tooth. Provisional restorative materials were placed in an open access following manufacturer guidelines. Streptococcus mutans was applied to the samples, and results were tabulated over the course of 4 weeks. RESULTS: Cavit and DuoTemp performed the best, and Ketac performed the worst. After 14 days, however, all materials leaked in over half of the samples. CONCLUSION: No material can be recommended as superior in providing a reliable seal after 14 days. PMID- 20305869 TI - Influence of root-surface conditioning with acid and chelating agents on clot stabilization. AB - OBJECTIVE: To compare the adhesion and maturation of blood components on chemically conditioned root surfaces. METHOD AND MATERIALS: Clinical root samples of human teeth were obtained (n = 150) and manually scaled. Five groups of 30 samples were treated as follows: (1) saline solution irrigation (control); (2) 24% EDTA gel; (3) 25% citric acid solution; (4) tetracycline solution (50 mg/mL); and (5) 30% sodium citrate solution. After these treatments, 15 samples of each group received a blood drop and were analyzed by SEM. The remaining 15 had their surface morphology evaluated for collagen fibrils exposure by SEM. Photomicrographs were analyzed according to the score of adhesion of blood components. Kruskal-Wallis and Dunn multiple comparison tests were employed. RESULTS: The control group was characterized by the absence of blood elements on the surface. The best result was observed in the citric acid group, which had a dense fibrin network with blood elements adhered. The EDTA group showed a moderate fibrin network formation. In contrast, a scarce fibrin network and a few cells were present in the tetracycline samples, and an absence of blood elements was found on sodium citrate specimens. The citric acid group was statistically different from the control group (P < .01). No differences were found among the control, EDTA, tetracycline, and sodium citrate groups (P > .05). CONCLUSION: Under these experimental conditions, citric acid is indicated to stabilize clots on the root surface, which act as a scaffold for connective tissue cell development. PMID- 20305870 TI - EJED and the Accademia Italiana di Conservativa. PMID- 20305871 TI - Non-carious cervical lesions associated with multiple gingival recessions in the maxillary arch. A restorative-periodontal effort for esthetic success. A 12-month case report. AB - Restoration of non-carious cervical lesions (NCCLs) represents a major challenge for resin materials due to the different adhesive properties of the tooth structure, the biomechanical aspects of the cervical area, and the difficulties in the access and isolation of the operative field. Furthermore, NCCLs should be approached with a complete understanding of the role played by the marginal periodontal tissue. Whenever a cervical lesion is associated with a gingival recession, the interplay between restorative dentistry and periodontology is decisive for full esthetic and long-term success. A case report is presented dealing with the treatment of NCCLs associated with multiple gingival recessions using a combined restorative and periodontal treatment with a 12-month follow-up. PMID- 20305872 TI - Composite resin rehabilitation of eroded dentition in a bulimic patient: a case report. AB - Eating disorders such as bulimia nervosa can have a significant impact on the structure of the teeth. Gastric acid not only causes enamel and dentin to dissolve but also causes a progressive deterioration of dental health, which leads to functional esthetic and biological consequences. According to the classic concepts of restorative dentistry, the rehabilitation of such clinical cases will involve numerous full crowns and root canal treatments, a process which is expensive financially, biologically, and in terms of time. However, the development of resin composite and adhesive systems has made it possible, today, to reconstruct teeth with minimal dental preparation. This article will look at the dental treatment of a bulimic patient who had numerous serious erosions with a significant loss of dental tissue. All teeth were reconstructed with a nano hybrid resin composite and, as very little preparation was necessary, the teeth's vitality was maintained and did not require laboratory collaboration. Furthermore, all biological, functional, and esthetic requisites were successfully met in a very short period of time. PMID- 20305873 TI - Adhesive restorations in the posterior area with subgingival cervical margins: new classification and differentiated treatment approach. AB - The aim of this article is to analyze some of the issues related to the adhesive restoration of teeth with deep cervical and/or subgingival margins in the posterior area. Three different problems tend to occur during restoration: loss of dental substance, detection of subgingival cervical margins, and dentin sealing of the cervical margins. These conditions, together with the presence of medium/large-sized cavities associated with cuspal involvement and absence of cervical enamel, are indications for indirect adhesive restorations. Subgingival margins are associated with biological and technical problems such as difficulty in isolating the working field with a dental dam, adhesion procedures, impression taking, and final positioning of the restoration itself. A new classification is suggested based on two clinical parameters: 1) a technicaloperative parameter (possibility of correct isolation through the dental dam) and 2) a biological parameter (depending on the biologic width). Three different clinical situations and three different therapeutic approaches are identified (1st, 2nd, and 3rd, respectively): coronal relocation of the margin, surgical exposure of the margin, and clinical crown lengthening. The latter is associated with three further operative sequences: immediate, early, or delayed impression taking. The different therapeutic options are described and illustrated by several clinical cases. The surgical-restorative approach, whereby surgery is strictly associated with buildup, onlay preparation, and impression taking is particularly interesting. The restoration is cemented after only 1 week. This approach makes it possible to speed up the therapy by eliminating the intermediate phases associated with positioning the provisional restorations, and with fast and efficient healing of the soft marginal tissue. PMID- 20305874 TI - CAD/CAM technology and zirconium oxide with feather-edge marginal preparation. AB - Clinical needs and growing patient expectations have forced modern dentistry to focus on finding ever simpler protocols and to develop materials which offer high performance in their mechanical resistance and esthetics. In recent years, the scientific community has been venturing into the world of CAD/CAM, a significant technological innovation imported from the world of engineering. This innovation has made it possible to exploit a material which has long been noted for its mechanical and mimetic qualities: zirconium oxide. While CAD/CAM is revolutionizing the laboratory work of dental technicians, the white color of zirconium has opened new avenues which may lead not only to new options for proper treatment planning, but also to new opportunities in the choice of materials to be used in prosthetic rehabilitation and variation of the types of preparations possible. The present paper will analyze the advantages and limitations of these methodologies, which are capable of simplifying clinical protocols and standardizing results. These technologies have instilled great enthusiasm in the profession due to their innovative nature, but this approach needs to be verified by further scientific evidence. PMID- 20305875 TI - Composite in everyday practice: how to choose the right material and simplify application techniques in the anterior teeth. AB - In daily practice, composites are the materials most commonly used for restorative dentistry. They are used for preventive seals, microinvasive restorations, build-ups and complex direct and indirect restorations in posterior sections. Indeed, it is in the anterior sections that composites have traditionally been used to the greatest effect, enabling clinicians to carry out complex restorations using direct techniques with notable esthetic and clinical results. Recent product developments combined with clinical research on stratification make it now possible to utilize new composites that have excellent opalescence and fluorescence characteristics and provide an excellent color range to choose from. It is however, a common complaint among clinicians that the layering techniques are rather complex and it is difficult to make the right color choice. Paradoxically, they say that the appearance on the market of sophisticated materials, designed to give ever better results in the medium and long term, only makes it more difficult to make the correct decision. Indeed, many of these colleagues, after the first buzz of enthusiasm, give up on the layering technique and opt for materials which they say are more simple or "mimetic." In the present article, the authors will discuss these topics and make suggestions on how to achieve high quality results every day, both from an esthetic and clinical point of view. However, predictability of the results is more important, as predictability provides advantages in terms of the quality of work and economy for clinicians and patients. PMID- 20305877 TI - Evaluation of placental glycogen storage in mild diabetic rats. AB - PURPOSE: To evaluate the placental glycogen storage and fetal development in the pregnancy of neonatally streptozocin-induced diabetic rats and to establish relation with glycemia and insulin levels. METHODS: At the birth day, 147 female rats were randomly distributed in two experimental groups: 1) Non-diabetic Group (Control, n=45) - received the vehicle; 2) Diabetic Group (STZ, n=102) - received 100 mg streptozocin/kg in neonatal period. At day 0 of pregnancy, adult female rats were included in the control group when presented glycemia below 120 mg/dL and, in the group STZ with glycemia between 120 and 300 mg/dL. At day 21 of pregnancy, blood samples were collected for glycemia and insulin determination, and placentas withdrawn for placental glycogen determination. The newborns (NB) were classified in small (SGA), appropriate (AGA) and large (LGA) for gestational age. RESULTS: Rats STZ presented higher glycemia at days 0 and 14 of pregnancy. At end of pregnancy, rats STZ showed higher proportion of NB SGA and LGA; reduced rate of NB AGA and unaltered glycemia, insulin and placental glycogen determinations. CONCLUSION: Mild diabetes altered the maternal glycemia in the early pregnancy, impairing future fetal development, but it caused no alteration on insulin and placental glycogen determination, confirming that this glycemic intensity was insufficient to change glycogen metabolism. PMID- 20305878 TI - Anatomopathological study of cardiomyopathy induced by doxorubicin in rats. AB - PURPOSE: The development of an experimental model of myocardiopathy induced by Doxorubicin in rats. METHODS: 16 wistar male rats were randomized in two groups: Group I (placebo) and Group II (Doxorubicin - 5mg/kg). After six months, the animals were subjected to cardiotomy and their hearts were weighted and submitted to transversal cuts, from which fragments for a macro and micro study were obtained. These fragments were studied considering their external and internal diameters and the thickness of the left ventricle (LV). The histological pieces were analyzed for the presence of fibrosis, cytoplasmic vacuolization, necrosis and size of nucleus variation. Data obtained was submitted to statistical analysis with Student's t test. RESULTS: The hearts of the animals in Group II increased 41% in relation to their weight; 33% in the internal diameter and 14% in the external diameter of the LV cavity; and 24% in the thickness of the wall. Fibrosis of the myocardial tissue was observed in 75% of the animals of Group II; all the animals presented miocyte cytoplasmatic vacuolization; myocardial necrosis was present in 75% of the animals; and 87/% presented variation in the size of myocite nuclei. The presence of polymorphonuclear cells was also observed. CONCLUSION: Doxorubicin was effective in the promotion of macro and microscopic alterations in the cardiac tissue of rats, possibly constituting a model for the experimental study of myocardiopathy. PMID- 20305879 TI - Eletrophysiological study of the caudal nerve on developing rats. AB - PURPOSE: To non-invasively study the sensory nerve conduction of the caudal nerve of normal developing rats. METHODS: Twenty normal Wistar male rats served as subjects. Caudal nerve conduction studies were performed at 60 days from birth and weekly at end of six consecutive weeks. The caudal nerve was stimulated distally and nerve potentials were recorded proximally on the animal's tail using common 'alligator' clips as surface electrodes. RESULTS: The amplitude and the conduction velocity of the caudal nerve sensory action potential increased linearly from 29+/-6 microV to 85+/-13 microV and from 34+/-3 m/s to 44+/-4 m/s, respectively, between the 8th and the 15th week of life. The equations of linear regressions were as followed: Amplitude (microV) = 8.1 x weeks - 34 (R(2) = 0.99) and NCV (m/s) = 1.2 x weeks + 25 (R(2) = 0.86). CONCLUSIONS: It was possible to study non-invasively the sensitive conduction of the caudal nerve of normal developing rats and describe reference values. The technique and data may be used as animal model in physiological and pathological studies. PMID- 20305880 TI - Optimization of visibility and quantification of aberrant crypt foci in colonic mucosa in Wistar rats. AB - PURPOSE: Test immersion of microscopy samples in water as an aid to visualizing and quantifying aberrant crypt foci (ACF) in rat colon mucosa. METHODS: Carcinogenesis was induced with azoxymethane in Wistar rats kept on a conventional diet or a hypercaloric diet containing unsaturated fat. Fifteen weeks after induction, colon samples were retrieved and fixated in a 10% formaldehyde solution. The samples were divided into segments (distal, middle, proximal) and stained with 1% toluidine blue. The technique tested in the study consisted of immersing microscopy samples in distilled water in order to eliminate the problem of light reflection known from conventional microscopy. RESULTS: When samples were immersed in water during microscopy, significantly more ACF could be visualized in all colon segments than with the conventional method proposed by Bird. CONCLUSION: Immersing microscopy samples in water aids the visualization and quantification of aberrant crypt foci in rat colon mucosa fixed in formaldehyde. PMID- 20305881 TI - Effects of plastic stenting in common bile duct of rats. A quantitative reaction analysis using collagen and elastin morphometry. AB - PURPOSE: To evaluate the effects of biliary stenting in rats through analysis of collagen and elastin deposition in the bile ducts. METHODS: Twenty male rats underwent midline laparotomy, duodenotomy and transampullary stenting of the common bile duct with a 22Fr plastic stent. Animals were randomized in 4 groups, with 5 components in each: (I) control, (II) biliary stenting for 7 days, (III) biliary stenting for 14 days, and (IV) biliary stenting for 30 days. Sections of the common bile duct were stained using Hematoxylin Eosin; Sirius Red to quantitate the amount of collagen present; and Weigert's Resorcin-fuchsin to quantitate the amount of elastin present. RESULTS: The percentage of area stained for collagen was 13.4; 21.5; 29.5 and 32.8, for groups I to IV, respectively. The percentage of area stained for elastin fibers was 7.0; 5.2; 4.0 and 2.9, for groups I to IV, respectively. Collagen/Elastin ratio was 2.4; 5.1; 11.0 and 14.4 for groups I to IV, respectively. CONCLUSIONS: The biliary stenting leads to collagen and elastin deposition in the bile ducts; and collagen deposition and collagen/elastin ratio are proportional to the period of stenting. PMID- 20305882 TI - End-to-side nerve repair using fibrin glue in rats. AB - PURPOSE: To evaluate axonal regeneration after end-to-side nerve repair with fibrin glue in rats. METHODS: Forty-five Wistar rats were divided into three groups: group A (n=15), were not submitted to surgery (control group); group B (n=15) were submitted to fibular transection without repair; and group C (n=15), were submitted to fibular transection with end-to-side nerve anastomosis using fibrin glue, in the lateral surface of an intact tibial nerve. The three groups were submitted to walking track (30 and 90 days) and posterior morphometrical analysis (90 days). RESULTS: The functional tests demonstrated that there was no difference in the walking track during the study in group A (p>0.05). The group B had walking pattern impairment in the two tests (p>0.05). The group C had walking pattern impairment in the first test, with important recovery in the second test (p<0.05). The morphometrical assessment revealed significantly higher number of regenerated mielinates axons in group C, compared to group B (p<0.05). CONCLUSION: The end-to-side nerve repair with fibrin glue shows axonal recovery, demonstrated through functional and morphometrical ways in rats. PMID- 20305883 TI - Postconditioning effect in the hepatic ischemia and reperfusion in rats. AB - PURPOSE: To evaluate the effect of postconditioning protection in liver tissue of rats submitted to ischemia and reperfusion. METHODS: 25 Wistar male rats were randomized in three groups: Group A (ischemia and reperfusion - I/R), with 10 rats, which was made ischemia by vascular clamp application in hepatic hilum for 30 minutes and reperfusion for 60 minutes by removal of the clamp; Group B (Postconditioning - IPo), with 10 rats, with same procedure plus postconditioning (3 cycles of reperfusion inserted by 3 cycles of ischemia, 30 seconds for each phase, between ischemia and reperfusion phases); and Group C (Sham), with 5 rats, which took place only laparotomy and manipulation of the hepatic hilum. Specimens were examined (histological evaluation) and dosage of serum AST and ALT was made. The statistical analysis was made with t Student test, with significant difference when p<0.05. RESULTS: In the Sham group there was no histological or enzymatic changes; In group A the mean tissue lesion was 1.6 and in group B 1.1 (p=0.014). In group A the mean ALT level was 355U/l and in group B was 175.9U/l (p=0.016). The mean of AST was 828.8U/l in group A and 295.5U/l in group B (p=0.001). CONCLUSION: The postconditioning was able to minimize the severity of liver injury in rats submitted to ischemia and reperfusion. PMID- 20305884 TI - Spring-mediated skull expansion: overall effects in sutural and parasutural areas. An experimental study in rabbits. AB - PURPOSE: The use of springs in cranial expansion has proven to be effective in the treatment of craniosynostosis. Spring-mediated expansion has been studied both in the sagittal and in parasagittal regions, especially in scaphocephaly. A rabbit model was used in the present study to analyze the effects of springs on the cranial vault and sutures. METHODS: Thirteen 4-week-old New Zealand rabbits were divided into 4 groups: in group I, only amalgam markers were used as control; in group II, amalgam markers were used and sagittal suturectomy was performed; in group III, amalgam markers were used, a sagittal suturectomy was performed and an expansible spring was fitted in the interparietal region and in group IV, markers were used and linear parasagittal craniectomy was carried out with springs. Animals were sacrificed after 2, 4, 8 and 12 weeks. Radiological control and histological analysis were performed in the area of spring implantation. RESULTS: In the groups using springs distraction of the craniectomy borders was greater than in those that did not use springs. New bone formation was observed in all groups, and was faster in group II. Bone growth started from the borders and depth. Bone regeneration presented a similar histological pattern in the groups with spring in the sagittal and parasagittal region. CONCLUSION: The rabbit model proved to be adequate for the analysis proposed by the study. The use of springs in the groups with sagittal and parasagittal osteotomy led to a similar distraction of amalgam markers and both groups had similar ossification histological pattern. PMID- 20305885 TI - The effect of copaiba balsam on Walker 256 carcinoma inoculated into the vagina and uterine cervix of female rats. AB - PURPOSE: To verify the copaiba balsam (Copaifera officinalis) effect on Walker 256 carcinoma inoculated into vagina and uterine cervix of rats. METHODS: Eighteen female Wistar rats weighing between 180-250g were used, distributed into 2 groups (GCop, GC). On the 1st day of the experiment, 0.3 ml of Walker 256 carcinoma (2x10(6) concentration) was inoculated in both groups; on the 3rd day of the experiment, it was given 4.8 ml/kg of distilled water to the GC group, and 4.8 ml/kg of copaiba balsam to the GCop group. On the 12th day, euthanasia was performed and the tumor was grafted, being weighted and verified its volume. The data were submitted to statistical analysis with ANOVA test. RESULTS: It was observed that copaiba balsam presented a negative inhibitory potential of 70%. CONCLUSION: The copaiba balsam stimulated the tumor growth. PMID- 20305886 TI - Hemodynamics and bispectral index (BIS) of dogs anesthetized with midazolam and ketamine associated with medetomidine or dexmedetomidine and submitted to ovariohysterectomy. AB - PURPOSE: To evaluate hemodynamics and bispectral index (BIS) in bitches anesthetized with ketamine and midazolam in combination with dexmedetomidine or medetomidine and submitted to ovariohysterectomy. METHODS: Twenty bitches pretreated with levomedetomidine and buprenorphine were anesthetized with 5 mg*kg(-1) ketamine and 0.2 mg*kg(-1) midazolam i.v. Continuous infusion of 0.4 mg*kg(-1)*h(-1) midazolam and 20 mg*kg(-1)*h(-1) ketamine was initiated in combination with DEX (n=10): 20 microg*kg(-1)*h(-1) dexmedetomidine or MED (n=10): 30 microg*kg(-1)*h(-1) medetomidine over 30 minutes. A pharmacokinetic study provided dexmedetomidine plasma concentration, set to be 3.0 ng*mL(-1). RESULTS: BIS decreased in both groups (P<0.05), but it was lower in DEX (P<0.05) as compared to MED. No differences were found in hemodynamic parameters (heart rate, systolic, diastolic and mean arterial pressure) between groups (P>0.05), but heart rate decreased in both groups, as compared to control values (P<0.05). Respiratory rate decreased (P<0.05) and expired end tidal CO(2) increased progressively (P<0.05) and similarly in both groups. Anesthetic recovery period was similar between groups (P<0.05) with no adverse effects. CONCLUSION: Continuous administration of dexmedetomidine with calculated plasma concentration equal to 3 ng.mL-1 in combination with midazolam and ketamine provides suitable anesthesia for spay surgery in bitches, hemodynamic stability and calm awakening with no adverse effects. PMID- 20305887 TI - Dartos flap coverage of the neourethra following repair for primary hypospadias, reoperative hypospadias and urethrocutaneous fistulas. It is a safe approach. AB - PURPOSE: Urethrocutaneous fistula and neourethral dehiscence are frequently seen complications of hypospadias surgery requiring reoperation. In this study we report the experience of one surgeon with dartos flap coverage in primary hypospadias, reoperative hypospadias and urethrocutaneous fistulas repair. METHODS: A total of 23 patients underwent hypospadias and urethrocutaneous fistulas repair from January 2006 to May 2009. Fourteen patients were operated on for primary hypospadias repair at our institution and 9 patients were admitted for hypospadias complications such as failed hypospadias repair and urethrocutaneous fistula. In all the patients, the dartos flap was dissected and transposed to cover the neourethra. Operative results were recorded. RESULTS: The primary surgical procedure was a one-stage repair in 61% (n = 14); tubularised incised plate (TIP) urethroplasty in 43% (n = 6) and a Mathieu procedure in 57% (n = 8). Urethrocutaneous fistulas complicating the previous initial hypospadias repair were anterior in 33% (n = 2), middle in 33% (n = 2) and proximal in 33% (n = 2). Repair of the fistula was successful on the first attempt in all patients. The reason for redo surgery in 3 patients was complete dehiscence and the patients had distal shaft hypospadias. CONCLUSION: Dartos flap coverage of the neourethra seems to be an effective method of reducing the fistulous complication rate following primary and secondary hypospadias repair. PMID- 20305888 TI - Accuracy of six minute walk test, stair test and spirometry using maximal oxygen uptake as gold standard. AB - PURPOSE: To assess the accuracy of the variables stair climbing time (SCt), stair climbing power (SCP), six-minute walk test distance (6MWT), and forced expiratory volume in 1 second (FEV1) using maximal oxygen uptake on exercise (VO(2)max) as the gold standard. METHODS: Tests were performed in 51 patients. FEV1 was measured by spirometry and 6MWT was performed in a flat 120-m corridor. Stair climbing test was performed on a 6-flight stairway to obtain SCt and SCP. VO(2)max was measured by ergospirometry, using the Balke protocol. Pearson's linear correlation and p values were calculated between VO2max and the other variables tested. For accuracy calculations, variable cutoff points were obtained through receiver operating characteristic (ROC) curves, dividing individuals into normal or unhealthy. Kappa statistic was used to calculate concordance. RESULTS: Accuracy was: SCt - 86%, 6MWT - 80%, SCP - 71%, FEV1(L) - 67%, FEV1(%) - 63%. SCt and 6MWT showed 93.5% sensitivity when combined in parallel, and 96.4% specificity in series. CONCLUSION: SCt presented the best accuracy. SCt and 6MWT combined showed nearly 100% sensitivity or specificity. Thus, these simple exercise tests should be more routinely used, especially when an ergospirometer is not available to measure VO(2)max. PMID- 20305889 TI - Costs of bariatric surgery in a teaching hospital and the financing provided by the Public Unified Health System. AB - PURPOSE: Analyze the effect of some measures on the costs of bariatric surgery, adopting as reference the remuneration of the procedure provided by the Unified Health System (SUS). METHODS: A retrospective evaluation conducted in the Costs Section of the University Hospital of Ribeirao Preto, of the costs involved in the perioperative period for patients submitted to bariatric surgery from 2004 to 2007. Changes in the routines and protocols of the service aiming at the reduction of these costs during the study period were also analyzed. RESULTS: Nine patients in 2004 and seven in 2007 submitted to conventional vertical banded 'Roux-en-Y' gastric bypass were studied. All patients presented good postoperative evolution. The average cost with these patients was R$ 6,845.17 in 2004. Even though an effort was made to contain expenditures, the cost in 2007 was of R$ 7,525.64 because of the increase in the price of materials and medicines. The Government remuneration of the procedure in the two years was R$ 3,259.72. CONCLUSION: Despite the adoption of diverse measures to reduce the expenditures of bariatric surgery, in fact there was an increase in the costs, a fact supporting the necessity of permanent evaluation of the financing of public health. PMID- 20305890 TI - Exhaled breath condensate collection for nitrite dosage: a safe and low cost adaptation. AB - PURPOSE: Standardization of a simple and low cost technique of exhaled breath condensate (EBC) collection to measure nitrite. METHODS: Two devices were mounted in polystyrene boxes filled either with crushed ice/salt crystals or dry ice/crushed ice. Blood samples were stored at -70 degrees C for posterior nitrite dosages by chemiluminescence and the Griess reaction. RESULTS: a) The use of crushed ice/dry ice or salt revealed sufficient EBC room air collection, but was not efficient for patients under ventilation support; b) the method using crushed ice/salt collected greater EBC volumes, but the nitrite concentrations were not proportional to the volume collected; c) The EBC nitrite values were higher in the surgical group using both methods; d) In the surgical group the nasal clip use diminished the EBC nitrite concentrations in both methods. CONCLUSIONS: The exhaled breath condensate (EBC) methodology collection was efficient on room air breathing. Either cooling methods provided successful EBC collections showing that it is possible to diminish costs, and, amongst the two used methods, the one using crushed ice/salt crystals revealed better efficiency compared to the dry ice method. PMID- 20305891 TI - New perspectives for optical techniques in diagnostic and treatment of hepatic diseases. PMID- 20305892 TI - Integrated pest management: theoretical insights from a threshold policy. AB - An Integrated Pest Management is formulated as a threshold policy. It is shown that when this strategy is applied to a food web consisting of generalist, specialist predators and endemic and pest prey, the dynamics can be stable and useful from the pest control point of view, despite the dynamical complexities inherent to the application of biocontrol only. In addition, pesticide toxicity depends rather on the species intrinsic parameters than on the chemical agent concentration. PMID- 20305893 TI - [Performance of Ceratitis capitata (Wiedemann) (Diptera: Tephritidae) in fruits: comparison of two laboratory populations]. AB - This study evaluated the influence of two fruits hosts (orange and papaya) on biological and behavioral parameters of two populations of Ceratitis capitata (Wiedemann) reared under laboratory conditions. One of these populations has been reared under laboratory conditions by 25 years without introduction of wild flies (Lab-pop), while the other has been maintained under the same conditions by 15 years but with occasional introduction of wild specimens (Hybrid-pop). The following parameters were analyzed: emergence percentage, life cycle duration (from eclosion to emergence), adult size, longevity, female fecundity and oviposition preference. The best performance of immatures of both populations was obtained on papaya as a host. Larvae reared on orange had longer life cycle, low emergence percentage and smaller adults. The fruit type did not affect fecundity and longevity of the Lab-pop, but in the Hybrid-pop males lived longer when reared on papaya, while females had higher longevity and fecundity when reared on orange. Females of both populations preferred to lay eggs in papaya (better host for larvae) when compared to orange. However, some eggs were deposited on orange only by females of Lab-pop, suggesting a lower ability for host selection of this population. These data are discussed regarding to the effects of continuous laboratory rearing on the biological parameters of this species. PMID- 20305894 TI - [Biological aspects of Cyclocephala verticalis burmeister (Coleoptera: Scarabaeidae)]. AB - Several coleopterans of the Scarabaeidae family (Pleurosticti) are reported as important pests of agricultural crops, but little information on their biology is available. We describe our observations on the biology of adult Cyclocephala verticalis Burmeister collected with light traps from January, 2006 to December, 2007, in Aquidauana, MS, Brasil. Field collected adults were taken to the laboratory and kept in plastic containers containing soil and seedlings of Brachiaria decumbens under controlled conditions (26 +/- 1 masculineC with 12h of photophase). The embrionary period of C. verticalis took 17.2 days in the average. The duration of first-, second- and third-instar larvae was 22.0, 23.7 and 138.1 days in the average, respectively. The prepupal stage took 12.7 days and the pupal stage 14.8 days. Adults obtained in laboratory lived 37.5 days. The complete cycle reached 228.6 days, making possible the development of a single generation per year. In laboratory conditions, the copulation lasted about 19 min and 20 seconds. The adults fly in a great amount in September and October, being this the main period of oviposition in the field. PMID- 20305895 TI - Dung beetle communities: a neotropical-north temperate comparison. AB - Dung beetle communities have been compared across north temperate latitudes. Tropical dung beetle communities appear to be more diverse based on studies using different methodologies. Here, we present results from a standardized sampling protocol used to compare dung beetle communities across five neotropical forests in Brazil and Ecuador and two warm, north temperate forests in Mississippi and Louisiana. Species richness in the tropical forests was three to seven times higher than the temperate forests, as would be expected by studies of other taxa across tropical and temperate latitudes. Average body size in the temperate forests was larger than the tropical forests, as predicted by Bergmann's rule. Dung beetle abundance and volume per trap-day were generally higher in Ecuador than Brazil, and higher in Mississippi than Louisiana, but there were no tropical temperate differences. Species rank-abundance curves were similar within countries and between countries. Rank-volume distributions indicated a smaller range of beetle body sizes in Ecuador versus Brazil or the USA. Community similarity was high within countries and low between countries. Community differences between Brazil and Ecuador sites may be explained by differences in productivity based on geological age of the soils. PMID- 20305896 TI - Alternative food sources and overwintering feeding behavior of the boll weevil, Anthonomus grandis boheman (Coleoptera: Curculionidae) under the tropical conditions of Central Brazil. AB - The boll weevil causes serious damage to the cotton crop in South America. Several studies have been published on this pest, but its phenology and behavior under the tropical conditions prevailing in Brazil are not well-known. In this study the feeding behavior and main food sources of adult boll weevils throughout the year in Central Brazil was investigated. The digestive tract contents of insects captured in pheromone traps in two cotton fields and two areas of native vegetation (gallery forest and cerrado sensu stricto) were analyzed. The insect was captured all through the year only in the cerrado. It fed on pollen of 19 different plant families, on Pteridophyta and fungi spores and algae cysts. Simpson Index test showed that the cerrado provided greater diversity of pollen sources. In the beginning of the cotton cycle, the plant families used for pollen feeding were varied: in cotton area 1, the weevil fed on Poaceae(50%), Malvaceae and Smilacaceae (25% each); in cotton area 2 the pollen sources were Malvaceae (50%), Asteraceae (25%) and Fabaceae and Clusiaceae (25% each); in the cerrado they were Chenopodiaceae (67%) and Scheuchzeriaceae (33%). No weevils were collected in the gallery forest in this period. After cotton was harvested, the family Smilacaceae was predominant among the food plants exploited in all the study areas. These results help to explain the survivorship of adult boll weevil during cotton fallow season in Central Brazil and they are discussed in the context of behavioral adaptations to the prevailing tropical environmental conditions. PMID- 20305897 TI - Comparative study of the stridulatorium sulcus, buccula and rostrum of nymphs of Triatoma klugi Carcavallo et al, Triatoma vandae Carcavallo et al and Triatoma williami Galvao et al (Hemiptera: Reduviidae). AB - Ultrastructural analysis of the ventral region of the head--rostrum, buccula and stridulatorium sulcus--of 1st, 3rd and 5th instars of Triatoma klugi Carcavallo et al, Triatoma vandae Carcavallo et al, and Triatoma williami Galvao et al, are described in here. Morphological differences in the analyzed structures for all three Triatoma species studied were detected under scanning electron microscopy, allowing their grouping by their morphological similarities. Species-specific differences at each nymphal development stage were analyzed as well. PMID- 20305898 TI - Isoenzymatic polymorphism in the leaf-cutting ant Atta capiguara Goncalves (Hymenoptera: Formicidae). AB - This study was carried out to analyze the genetic population structure of Atta capiguara from 12 nests collected in Tapejara in the state of Parana, Brazil, using isoenzyme polymorphisms. The analyzed isoenzymes were esterases (EST-EC 3.1.1.1), acid phosphatase (ACP-EC 3.1.3.2) and carbonic anhydrase (CA-EC 4.2.1.1). Ten loci were found in A.capiguara and four polymorphic loci were detected. The observed heterozigosity (0.0296) was low when compared to the expected heterozigosity (0.1461). The high value of F(IS) (0.7954) shows an excess of homozygous genotypes probably caused by inbreeding. PMID- 20305899 TI - A new species of Metriocnemus van der Wulp (Diptera: Chironomidae) with a tentative phylogeny of the genus. AB - The male and female of the new species Metriocnemus puna sp. n from the Argentinean Puna are described and illustrated. A parsimony analysis including 24 well-described species of the genus plus the new species based on the adult male was conducted in order to access the phylogenetic position of the new species and to provide the first phylogenetic hypothesis for the genus. PMID- 20305900 TI - [A new species of Xylocopa (Monoxylocopa) Hurd & Moure and new records of X. abbreviata Hurd & Moure (Hymenoptera: Apidae)]. AB - Xylocopa (Monoxylocopa) macambirae sp. nov. is described from specimens collected mainly in areas at moderately high altitude of Northeastern brazil, inside the caatinga semi-arid domain. Additionally, a complementary diagnosis for the subgenus is presented. PMID- 20305901 TI - New species of Tanytarsus van der Wulp (Diptera: Chironomidae) from Sao Paulo State, Brazil. AB - Tanytarsus lenyae sp. n., T. giovannii sp. n., T. fittkaui sp. n. and T. alfredoi sp. n. from Sao Paulo State (Brazil) are described and diagnosed, the first as adult male and pupa, and the remaining as male, pupa and larva. The species were collected in areas of Cerrado, at the boundaries of Sao Carlos city. Complete diagnoses and drawings of the species are given. The imagos can be separated from other species of Tanytarsus van der Wulp mainly by differences in the antennal ratio, dorsomedian extension of the eyes, the thorax and wing setation, the shape of anal tergal bands, the anal point armament and the shape of superior volsella, digitus and median volsella. The pupae are characterized by the thoracic horn armament, the arrangement of the precorneals, the shape of anal comb and the abdominal setation. The larvae can be separated by differences in the antennal pedestal, the sclerotization of the second antennal segment, the size of Lauterborn organ pedicels, the shape of the clypeal seta S3 and the sclerotization of the mentum. Apparently, the four new species are not closely related, and the anal point armament alone would be enough to separate one species from the other. PMID- 20305902 TI - A new species of Moneuptychia Forster (Lepidoptera: Satyrinae: Euptychiina) from central Brazil. AB - This paper describes a new species of Moneuptychia Forster from the cerrado in the Federal District and Goias region in central Brazil, and from highland open vegetation (campos de altitude) of Minas Gerais and Parana. We provide details of the adult morphology and discuss the new species placement in the genus Moneuptychia. PMID- 20305903 TI - [Effects of landscape structure and Eucalyptus genotype on the abundance and biological control of Glycaspis brimblecombei Moore (Hemiptera: Psyllidae)]. AB - Glycaspis brimblecombei Moore is an Australian native pest of Eucalyptus detected in Brazil in 2003. Since then, it has spread fast and colonized plantations in several states of the country. This study aimed to investigate the influence of cerrado remnants on the abundance and biological control of G. brimblecombei. We placed yellow sticky card traps to capture insects in four plantations of hybrid clones of Eucalyptus urophylla x Eucalyptus grandis ('Urograndis') and four plantations of E. urophylla x Eucalyptus camaldulensis ('Urocam'). Traps were placed in three areas of these plantations: center, border with cerrado and border without cerrado. We also collected leaves from the same clones to estimate psyllid egg and lerp abundance. The abundance of G. brimblecombei was lower in the plantation-cerrado border, and the inverse pattern was observed for microhymenopterans. The leaf abaxial surface showed a higher abundance of eggs and nymphs, probably as a consequence of a lower parasitism rate and mechanical removal by wind and rain. Egg number was higher on Urograndis than in Urocam clones, but the number of psyllid lerps was higher in the latter. Thus, the establishment of first instars is probably a critical event to psyllid infestation, and these differences may be caused by morphological, anatomical and biochemical leaf features of distinct clones. Our results suggest that the maintenance of native vegetation around plantations is a promising management practice to promote the natural biological control of G.brimblecombei, a strategy that would also enhance the preservation of cerrado remnants. PMID- 20305904 TI - [Influence of the webbing produced by Oligonychus ilicis (McGregor) (Acari: Tetranychidae) on associated predatory phytoseiids]. AB - Oligonychus ilicis (McGregor) is among those mite species that can cause damage to coffee plants (Coffea spp.). Species of Phytoseiidae acari are considered the most important and studied predatory mites. The objective of this study was to evaluate the effects of the webbing produced by O.ilicis on its predation by females of the phytoseiids Iphiseiodes zuluagai Denmark & Muma, Euseius citrifolius Denmark & Muma and Amblyseius herbicolus (Chant). Four bioassays were conducted, with three treatments and ten replicates. Each replicate consisted of 25 O.ilicis per experimental unit (a leaf disc of Coffea arabica) according to the tested developmental stage, in independent experiments. To spin the web, 15 adult females were put on each experimental unit for 24h; females were then removed, leaving only the web, and predators and prey to be tested were introduced. Predation was assessed after 24h. In the presence of webbing, the consumption of eggs, larvae and nymphs by I.zuluagai and eggs and larvae by E.citrifolius was lower. For A.herbicolus, egg predation was lower, but larval predation did not vary significantly and predation of nymphs and adults was higher in the presence of webbing. Predators as a whole were more efficient consuming larvae regardless of the presence of webbing. Considering the stages of O.ilicis altogether, webbing reduced the predation potential of I.zuluagai and E. citrifolius, but not of A. herbicolus. PMID- 20305905 TI - Spread of phosphine resistance among brazilian populations of three species of stored product insects. AB - The resistance to fumigant insecticides in stored-products insects is often recorded. Several factors influence the evolution of insecticide resistance. Among these, the frequency of applications and the migration of resistant populations are of primary importance for the stored-product insects. The aim of this study was to characterize the spectrum and investigate the status of phosphine resistance in Brazil, in 13 populations of the Coleoptera Tribolium castaneum Herbst (Tenebrionidae), ten populations of Rhyzopertha dominica (Fabr.) (Bostrichidae), and eight populations of Oryzaephilus surinamensis (L.) (Silvanidae). The pattern of resistance dispersion in the populations of these species was also verified. The bioassays for the detection of phosphine resistance followed the FAO standard method. To test the influence of migration in the evolution of the phosphine resistance, the difference of mortality in the discriminating concentration and the geographical distance among each pair wise combination of collection sites were correlated. None of the populations exhibited mortality above 90% in the discriminating concentration, for the three species. Mortality in the discriminating concentration increased with the geographical distance for R.dominica and O.surinamensis. However, no significant linear response was observed among the variables for T.castaneum populations. These results suggest that the dispersion of insects and the local selection are relevant in the evolution of the phosphine resistance in populations of R.dominica and O.surinamensis. In contrast, grain trade and local selection are probably the factors that determine the evolution of the phosphine resistance in populations of T. castaneum. PMID- 20305907 TI - Phlebotomine sand flies (Diptera: Psychodidae) of the state of Minas Gerais, Brazil. AB - The phlebotomine sand fly fauna of the State of Minas Gerais is presented based on an extensive review of the literature. The fauna, which is a rich one, is currently known to consist of at least 93 species included in 16 genera. The genus Evandromyia (16 spp.) is the most representative one, followed by Micropygomyia (13 spp.), Psathyromyia (12 spp.), Brumptomyia (11 spp.), Pintomyia (9 spp.), Lutzomyia (7 spp.), Psychodopygus (7 spp.), Martinsmyia (4 spp.), Nyssomyia (3 spp.), Deanemyia (2 spp.), Expapillata (2 spp.), Pressatia (2 spp.), and Sciopemyia (2 spp.). The genera Bichromomyia, Trichopygomyia, and Migonemyia are represented by only one species. An updated list of phlebotomine sand fly species occurring in Minas Gerais is provided. Finally, the importance of the species of public health concern is discussed. PMID- 20305906 TI - Population dynamics and damage caused by the leafminer Liriomyza huidobrensis Blanchard (Diptera: Agromyzidae), on seven potato processing varieties grown in temperate environment. AB - The leafminer Liriomyza huidobrensis Blanchard is considered a key pest for potatoes in Argentina. Population dynamics and leaf damage caused by the leafminer on seven selected potato processing varieties were assessed at Balcarce during the 2002 and 2003 growing seasons. Adult population dynamic was monitored using yellow sticky traps, while leaf damage (punctures and mines) was assessed using a damage index scale from low to severe. Liriomyza huidobrensis adults were present throughout the growing season and the population increased along crop development. The same was true for all varieties regarding larval damage, being low on early crop stages and severe late in the season. Varieties were grouped in two different categories according to damage scale index. Shepody, Kennebec, Frital and Innovator showed a higher damage index when compared with Santana, Ranger Russet and Russet Burbank, which exhibited a lower damage. Moreover, it could be assumed that damage was related to the foliage greenness, with light green colored varieties (Shepody, Kennebec, Frital and Innovator) being more attractive and affected by L. huidobrensis. PMID- 20305908 TI - [Composition, abundance and infestation rate of ant species in a children's hospital in the city of Palmas, Tocantins, Brazil]. AB - This first survey of the ant fauna in a children's hospital in the city of Palmas, state of Tocantins, compares species composition, abundance and infestation rate of ants between rainy and dry seasons, day and night periods, and among 15 hospital sectors. Forty-eight collections, being 12 diurnal and 12 nocturnal in each season using five attractive baits distributed per sector, maintained for 3h per sampling. A total of 34,309 ants were collected, distributed in 12 species: Acromyrmex sp., Brachymyrmex sp., Camponotus spp. (four morphospecies), Dorymyrmex sp., Tetramorium sp., Solenopsis globularia (Creighton), Solenopsis saevissima Smith, Tapinoma melanocephalum (Fabricius) and Paratrechina longicornis (Latreille). The hospital presented an average building infestation rate (40.3%), when compared with hospitals from other Brazilian regions. In general, there was no difference in the species composition between seasons and the period of the day, although abundance of ants was higher at night. The dry season and the nocturnal period showed the highest infestation rate, mainly by T.melanocephalum and S.globularia. Gynecologic ward, lactation unit, preconception and pediatric ward access ramp showed higher infestation rate, although these varied between seasons. The significant infestation levels by the three species above, especially in sectors with restricted access such as lactation unit, laboratory, Intensive Care Unit e surgery center, indicate potential risks for contamination of patients by multi resistant pathogens possibly present in ants' bodies, as verified in others studies. PMID- 20305909 TI - [First occurrence of Alcaeorrhynchus grandis (Dallas) (Hemiptera: Pentatomidae) preying on defoliating caterpillars of oil palm in the State of Para, Brazil]. AB - The oil palm Elaeis guineensis is usually attacked by pests, particularly, defoliating caterpillars. Between 2004 and 2006 a stinkbug predator (Asopinae) was registered preying on caterpillars of Brassolis sophorae L., Opsiphanes invirae Hubner (Lepidoptera: Nymphalidae) and Sibine spp. (Lepidoptera: Limacodidae), reducing their populations in commercial oil palm plantations in the State of Para, Brazil. Specimens of the natural enemy were collected, mounted, and identified as Alcaeorrhynchus grandis (Dallas) (Hemiptera: Pentatomidae), corresponding to the first report of the occurrence of this stinkbug attacking defoliating caterpillars of oil palm in Brazil. PMID- 20305910 TI - Eufriesea pulchra smith (Hymenoptera: Apidae: Euglossini): extended geographic distribution and filling gaps in Mato Grosso state, Brazil. AB - This study was conducted in the Cotriguacu district, situated on the bank of the Juruena River, in Mato Grosso state. The collects were carried out from August 22 to 25, 2007 with chemical baits to attract male orchid bees. The bees were captured on a daily basis, from 8 a.m. to 12 p.m. Of the 89 males captured three belonged to Eufriesea pulchra Smith. Before the present study, E.pulchra had been reported in the states of Para, Amazonas, Amapa, (dubiously) Sao Paulo, and Maranhao. This occurrence extends its geographical distribution range by 900 to 2,000 km southwards in South America, as it is now recorded in the Amazon and Platina basins. PMID- 20305911 TI - Presence of the fire ant Solenopsis invicta (Westwood) (Hymenoptera: Formicidae) stimulates burrowing behavior by larvae of the sandfly Lutzomyia longipalpis (Lutz & Neiva) (Diptera: Psychodidae). AB - The sandfly Lutzomyia longipalpis (Lutz & Neiva) vectors leishmaniasis in the neotropics. Although much is known about the biology of adult flies, little is known about interactions with its natural enemies. Here, we examined behavior of larvae of L4 L.longipalpis on a soil substrate when exposed to the fire ant Solenopsis invicata (Westwood). When ants were absent, most larvae tended to remain at or close to the soil surface, but when ants were present the larvae burrowed into the soil. Sandflies seek refuges in the presence of generalist predators, thus rendering them immune to attack from many potential enemies. PMID- 20305912 TI - First report of the citrus Hindu mite, Schizotetranychus hindustanicus (Hirst) (Prostigmata: Tetranychidae), in Brazil. AB - The citrus Hindu mite, Schizotetranychus hindustanicus (Hirst), is reported for the first time in Brazil and for the second time in South America. Mite specimens were collected from citrus in the municipality of Boa Vista, State of Roraima, northern Brazil. Symptoms associated with S.hindustanicus infestations on citrus are described. The importance of avoiding dissemination of this mite to the main citrus production areas in Brazil is discussed. PMID- 20305914 TI - The rescue surgeon. PMID- 20305915 TI - Risk factors for acute renal failure after heart surgery. AB - OBJECTIVE: The aim of the present study was to identify risk factors for acute renal failure in patients with normal levels of serum creatinine who had undergone coronary artery bypass graft (CABG) surgery and/or valve surgery. METHODS: Data from a cohort of 769 patients were assessed using bivariate analyses and binary logistic regression modeling. RESULTS: Three hundred eighty one patients underwent CABG, 339 valve surgery and 49 had undergone both simultaneously. Forty six percent of the patients were female and the mean age was 57 +/- 14 years (13 to 89 years). Seventy eight (10%) patients presented renal dysfunction postoperatively, of these 23% needed hemodialysis (2.4% of all patients). The mortality for the whole cohort was 10%. The overall mortality for patients experiencing postoperative renal dysfunction was 40% (versus 7%, P < 0.001), 29% for those who did not need dialysis and 67% for those who needed dialysis (P = 0.004). The independent risk factors found were: age (P < 0.000, OR: 1.056), congestive heart failure (P = 0.091, OR: 2.238), COPD (P = 0.003, OR: 4.111), endocarditis (P = 0.001, OR: 12.140), myocardial infarction < 30 days (P = 0.015, OR: 4.205), valve surgery (P = 0.016, OR: 2.137), cardiopulmonary bypass time > 120 min (P = 0.001, OR: 7.040), peripheral arterial vascular disease (P = 0.107, 2.296). CONCLUSION: Renal dysfunction was the most frequent postoperative organ dysfunction in patients undergone CABG and/or valve surgery and age, congestive heart failure, COPD, endocarditis, myocardial infarction < 30 days, valve surgery, cardiopulmonary bypass time >120 min, and peripheral arterial vascular disease were the risk factors independently associated with acute renal failure (ARF). PMID- 20305916 TI - New technique: Norwood operation with regional cerebral and coronary perfusion. AB - OBJECTIVE: To assess the immediate result of the modified Norwood procedure with new technique of anterograde regional cerebral perfusion (ARCeP) and retrograde regional coronary perfusion (RRCoP) in substitution of profound hypothermia and circulatory arrest in children with hypoplastic left heart syndrome (HLHS) with extremely hypoplastic ascending aorta (HA). METHODS: In the period of December of 2006 to February 2008 the modified Norwood procedure with tube between the right ventricle and pulmonary arteries or Sano shunt was performed in eight children with HLHS and with ascending aorta diameter less than 3 mm, (four male and four female) with median age of 9.2 days (ranging from 1 to 29 days) and median weigh of 3.3 kg (ranging from 2.7 to 3.8 kg). We used cardiopulmonary bypass and hypothermia at 25 masculineC with two venous cannulas and suture with a polytetrafluoroethylene graft sutured to the innominate artery as an arterial line and used to ARCeP. The RRCoP was performed by a deviation in the arterial line and placement of a catheter in the ascending aorta. The immediate surgical results and the clinical neurological manifestation were assessed. RESULTS: The immediate surgical results revealed mortality of 25% and there were absence of neurological injury at clinical examination. CONCLUSIONS: The modified Norwood procedure can be accomplished with ARCeP and RRCoP in children with HLHS with HA with satisfactory immediate surgical result and without neurological complications. PMID- 20305917 TI - Does the coronary disease increase the hospital mortality in patients with aortic stenosis undergoing valve replacement? AB - OBJECTIVES: With the increase in life expectancy occurred in recent decades, it has been noted the concomitant increase in the prevalence of aortic stenosis and degenerative disease of atherosclerotic coronary artery. This study aims to evaluate the influence of atherosclerotic coronary artery disease in patients with critical aortic stenosis undergoing isolated or combined implant valve prosthesis and coronary artery by pass grafting. METHODS: In the period of January 2001 to March 2006, there were analyzed 448 patients undergoing isolated implant aortic valve prosthesis (Group I) and 167 patients undergoing aortic valve prosthesis implant combined with coronary artery bypass grafting (Group II). Pre- and intra-operative variables elected for analysis were: age, gender, body mass index, stroke, diabetes mellitus, chronic obstructive pulmonary disease, rheumatic fever, hypertension, endocarditis, acute myocardial infarction, smoking, Fraction of the left ventricular ejection, critical atherosclerotic coronary artery disease, chronic atrial fibrillation, aortic valve operation prior (conservative), functional class of congestive heart failure, value serum creatinine, total cholesterol, size of the prosthesis used, length and number of distal anastomoses held in myocardial revascularization, duration of cardiopulmonary bypass and aortic clamping time. The statistical study employed invariant and multivariate analysis. RESULTS: Hospital mortality was 14.3% (64 deaths) in Group I, and 14.5% (58 deaths) in patients with atherosclerotic coronary artery disease associated criticism (Group IB) and 12.8% (six deaths) in which had this association (Group IA). Hospital mortality in Group II was 17.6% (29 deaths), and 16.1% (20 deaths) in patients undergoing implantation of prosthetic aortic valve combined to complete myocardial revascularization (Group II) and 20.9% (nine deaths) in the myocardial revascularization with incomplete (Group IIB). CONCLUSIONS: In patients undergoing implant isolated from aortic valve prosthesis, the presence of atherosclerotic coronary artery disease associated critical in at least two arteries, influenced the hospital mortality. In patients undergoing surgical treatment combined the number of coronary arteries with critical atherosclerotic disease and extent of coronary artery bypass grafting (complete or incomplete), did not affect the hospital mortality, but the realization of more than three anastomoses in the distal myocardial revascularization interfered. PMID- 20305918 TI - Fontan operation: a technique in evolution. AB - OBJECTIVES: Recent experimental flow studies based on angiography and magnetic resonance have shown that total cavopulmonary anastomosis (TCPA) is a valid concept for surgical treatment of many congenital heart defects, but there is not agreement of the best surgical arrangement. Our purpose is to analyze the immediate results with three different techniques of TCPA. METHODS: We sought to analyze retrospectively all TCPA realized from January 2005 to July 2008; there were 40 patients, all with previous Glenn anastomosis, with mean age of 6.4 +/- 3.2 years. Three different techniques were employed: Group 1 (G1) lateral tunnel, Group 2 (G2) extracardiac conduits, Group 3 (G3) intracardiac conduit directed to the left pulmonary artery. All patients had a fenestration done. RESULTS: G1 had 11 patients, G2 10 patients and G3 19 patients. Preoperative data were similar in the 3 groups (P>0.05). Surgical mortality was higher in Groups 1 and 2 (9.1% and 10%) compared to Group 3 (0%) but there was no statistical significance (P=0.3841). Pleural effusion was absent in Group 3 (0%), which was statistically significant in relation to the other groups (P=0.0128). The hospitalization time was also significantly lower in G3 (8 days) in relation to G1 (18 days) and G2 (13 days) (P=0.0164). CONCLUSION: Intracardiac TCPA was associated with lower postoperative morbidity and is currently our preferred technique. PMID- 20305919 TI - Surgical reverse remodelling of the left ventricle: 111 months of follow-up. AB - OBJECTIVE: To present the Instituto de Cirurgia Cardiovascular do Oeste do Parana' (ICCOP) surgical experience, on the treatment of left ventricle aneurysms, by endoventriculoplasty, with septal exclusion (EVSE), and a 111 months follow-up. METHODS: Between April 1999 and April 2006, 28 patients were submitted to EVSE, by the author. Pre, trans and late post clinical and echocardiographic variables were analyzed retrospectively. Mean age was 59.0 +/- 9.5 years, being 23 male patients. Seventeen patients were in NYHA functional class IV and the mean EuroScore was 8.2 +/- 2.3. The mean pre-operative values for ejection fraction, end systolic and diastolic left ventricular volumes were 32.3 +/- 9.2%, 113.9 +/- 36.0 ml e 179.2 +/- 48.4 ml, respectively. The BraziliAnVErsion of the SF36 quality of life questionnaire was applied in the late follow up period. RESULTS: Four patients died in the immediate post operative period, being the major cause of morbidity low cardiac output syndrome and arrhythmias. The mean follow-up period was 5.6 +/- 3.2 years. Left ventricle's ejection fraction and aortic cross clamping time were the significant factors for hospital and late mortality with P = 0.0222 and P = 0.0123, respectively. Actuarial survival curve showed a survival of 82.1 +/- 7.2%, and 54.7 +/- 22.9%, pre and post 107 months, of follow-up. CONCLUSION: EVSE' surgery is an effective option to treat this group of patients, with improvement of left ventricular function (from 32.3 to 46.4%) and patients' quality of life. PMID- 20305920 TI - Relationship on walk test and pulmonary function tests with the length of hospitalization in cardiac surgery patients. AB - OBJECTIVE: The lung function is identified as a predictor of time of hospitalization in heart surgery. Meanwhile sixminute walk test has been used to establish functional capacity of cardiac patients, however there are few studies that correlate it with the length of hospital stay. The aim of this research was to determine whether there is correlation of preoperative and postoperative lung function and the ability of walking during the hospital stay. METHODS: A prospective cohort with 18 patients was performed, being 8 males and 10 females, with age above 40 years (medium 64.89 +/- 6.95 years). Patients where admitted for coronary artery bypass graft surgery and/or exchange valve. To characterize the pulmonary function, patients were submitted to spirometry in preoperative and the 5th postoperative day. In the latter period was also a test for 6 minutes walk (6MWT) to characterize the ability to walk. RESULTS: There was not significant correlation of preoperative and postoperative pulmonary function with length of hospital stay. Only the distance covered in 6MWT showed a significant negative correlation (rho= 0.62) with length of stay. The distance in 6MWT obtained a significant positive correlation with forced vital capacity (r=0.59) and first second of a maximal forced expiratory manoeuvre (r=0.52). CONCLUSION: These results suggest that patients with increased postoperative capacity to walk have a shorter time of hospitalization and it also suggest that the distance in the 6MWT can better represent the functional capacity of these patients than pulmonary function alone. PMID- 20305921 TI - Mitral valve repair in rheumatic patients with mitral insuficiency: twenty years of techniques and results. AB - OBJECTIVE: Mitral valve repair in rheumatic patients is still a challenge. The purpose of this study is to analyze the results of mitral valve repair in rheumatic patients in the Heart Institute University of Sao Paulo Medical School. METHODS: Were analyzed retrospectively, between 1985 and 2005, 330 patients submitted to mitral valve repair in the Heart Institute of Sao Paulo. The mean age was 26.9 +/- 15.4 years and 57.6% were female. According do clinical evaluation, 39.5% of patients were in NYHA functional class IV. The most common techniques employed were bovine pericardial strip annuloplasty in 48.4% patients and Carpentier ring annuloplasty in 22.6%. Shortening of chordae (20%) and papillary muscle splitting (17.8%) were the most common associated techniques performed. Tricuspid valve repair (26.7%) and aortic valve replacement (27.2%) were the most common associated procedures. RESULTS: The hospital mortality was 0.9% (three patients), two of them in children with active rheumatic fever. Linearized rates of thromboembolism, endocardite, reoperation and late death were 0.2%, 0.2%, 3.5% and 0.5% patients-year, respectively. Actuarial survival in 20 years was 86.4 +/- 6.6%. Freedom from reoperation in 20 years was 30.3 +/- 11.1%. CONCLUSION: Mitral valve conservative surgery in rheumatic patients is a feasible procedure with low operative mortality. PMID- 20305922 TI - Does the pain disturb the respiratory function after open heart surgery? AB - OBJECTIVE: The post operative pain after open heart surgeries had been often reported. Meager reports about respiratory function and pain correlation had been reported. The aim of this article is to assess the pain intensity and location during hospital admittance and its effect on pulmonary function in patients underwent elective cardiac surgery. METHODS: Pulmonary function (lung volumes, respiratory pressures and peak expiratory flow) was assessed at the preoperative and post-operative time (1, 3 and 5 days) by ventilometer, manovacuometer and peak flow meter measurements. The assessment of pain intensity was carried out with a visual analogue scale for pain. RESULTS: The majority of pain site was on sternotomy incision (50% of patients) and the intensity was higher at the first postoperative day (8.32 by visual scale measurement). All pulmonary variables decreased on post-operative time when compared to baseline values. All respiratory variables remained lower than to pre-operative time at fifth postoperative time (P > 0.05), with exception for respiratory rate. The pain and maximal inspiratory pressure showed a negative correlation at the first postoperative day (P = 0.019). CONCLUSION: Postoperative pain decreased lung function in patients precluding deep inspirations, in special, at the first post operative day. PMID- 20305923 TI - Pain and pulmonary function in patients submitted to heart surgery via sternotomy. AB - OBJECTIVE: To investigate the pulmonary function and pain in adult patients undergoing heart surgery via sternotomy and to verify possible correlations of these variables with the characteristics of the surgical procedure and hospital stay. METHODS: A cross-sectional study was carried out of 70 individuals undergoing heart surgery. The lung function was assessed before and after surgery by spirometry and incentive spirometry. Details of the surgical procedure were studied and patients were followed up postoperatively using a visual analogue scale and design of the human body to evaluate pain. RESULTS: The pulmonary function was significantly impaired in the postoperative compared to preoperative period (P <0.01). The pain was centered in the region of the sternotomy and persisted until at least the 5th postoperative day. There was a correlation between pain and the parameters of pulmonary function (forced expiratory volume in 1 second - percentage: r = -0.271, P <0.047; peak expiratory flow: r = 0.357, P <0.008; and maximum inspiratory volume: r = -0.293, P <0.032). There was no significant correlation between pain and other variables. CONCLUSION: There was significant impairment of lung function which had not recovered completely on the 5th postoperative day. Pain was a complaint that persisted throughout the study period. The parameters of pulmonary function showed a significant relationship with pain. There was no correlation between pain and the characteristics of individuals, the surgical procedure or the length of hospital stay. PMID- 20305924 TI - Trends in animal experimentation. AB - INTRODUCTION: The search of the understanding of etiological factors, mechanisms and treatment of the diseases has been taking to the development of several animal models in the last decades. OBJECTIVE: To discuss aspects related to animal models of experimentation, animal choice and current trends in this field in our country. In addition, this study evaluated the frequency of experimental articles in medical journals. METHODS: Five Brazilian journals indexed by LILACS, SciELO, MEDLINE, and recently incorporate for Institute for Scientific Information Journal of Citation Reports were analyzed. All the papers published in those journals, between 2007 and 2008, that used animal models, were selected based on the abstracts. RESULTS: Of the total of 832 articles published in the period, 92 (11.1%) experimentation papers were selected. The number of experimental articles ranged from 5.2% to 17.9% of the global content of the journal. In the instructions to the authors, four (80%) journals presented explicit reference to the ethical principles in the conduction of studies with animals. The induced animal models represented 100% of the articles analyzed in this study. The rat was the most employed animal in the analyzed articles (78.3%). CONCLUSIONS: The present study can contribute, supplying subsidies for adoption of future editorials policies regarding the publication of animal research papers in Brazilian Journal of Cardiovascular Surgery. PMID- 20305925 TI - Coronary dominance patterns in the human heart investigated by corrosion casting. AB - OBJECTIVES: The aim of this work was to analyze the dominance patterns of the circulation of the human heart, the number of branches from the right coronary artery to the left ventricle, the number of branches from the left coronary artery to the right ventricle and the frequency and location of intercoronary anastomoses. METHODS: Casts were made of 25 hearts by the injection of colored acrylic resin and subsequent corrosion using hydrochloric acid at the experimental surgery laboratory of Furb. Specimens with lesions or scars were discarded. RESULTS: The hearts, from both men (17 - 68%) and women (8 - 32%), had a mean age of 40.2 (15 to 70) years-old. Right dominance occurred in 18 (72%) subjects, with 1, 2, 3 and 4 branches leading to the left ventricle in 2, 14, 2 and 2 casts, respectively. Left dominance occurred in 5 (20%) with 1 branch leading to the right ventricle in 4 molds and 2 in one. Balanced circulation was observed in two molds (8%). There were significant differences between right and left dominance (alpha > 5%) and between right dominance and balanced circulation (alpha > 5%), however the same was not true between left dominance and balanced circulation (alpha < 5%). CONCLUSION: The most common form of coronary circulation is right dominance with an average of 2.16 branches leading to the left ventricle: when dominance is left, the average is 1.2 branches. No intercoronary anastomoses were observed. PMID- 20305926 TI - High-dose aprotinin does not affect troponin I, N-Terminal pro-B-type natriuretic peptid and renal function in children submitted to surgical correction with extracorporeal circulation. AB - OBJECTIVE: To evaluate if the use of hemostatic high-dose aprotinin seems influence to myocardial, renal and metabolic functions in children submitted to surgical correction with extracorporeal circulation (ECC). Material and Methods A prospective randomized study was conducted on children aged 30 days to 4 years submitted to correction of acyanogenic congenital heart disease with ECC and divided into two groups: Control (n=9) and Aprotinin (n=10). In the Aprotinin Group the drug was administered before and during ECC and the myocardial and multiorgan dysfunctions were analyzed on the basis of clinical and biochemical markers. Differences were considered to be significant when P<0.05. RESULTS: The groups were similar regarding demographic and intraoperative variables, except for a greater hemodilution in the Aprotinin Group. The drug had no benefit regarding time of mechanical pulmonary ventilation, permanence in the pediatric postoperative intensive care unit (ICU) and length of hospitalization, or regarding the use of inotropic drugs and renal function. The partial arterial oxygen pressure/inspired oxygen fraction ratio (PaO2/FiO2) was significantly reduced 24h after surgery in the Control Group. Blood loss was similar for both groups. Cardiac troponin I (cTnI), creatine kinase MB fraction (CKMB), serum glutamic-oxaloacetic transaminase (SGOT) and the aminoterminal fraction of natriuretic peptide type B (NT-proBNP) did not differ significantly between groups. Post-ECC blood lactate concentration and metabolic acidosis was more intense in the Aprotinin Group. There were no complications with the use of aprotinin. CONCLUSION: High-dose aprotinin did not significant influence in serum markers troponin I, NT-proBNP and renal function, but did associated with hemodilution, blood lactate concentration and metabolic acidosis more intense. PMID- 20305927 TI - Flow visualization in blood aspirator and cardiotomy reservoir used in cardiopulmonary bypass. AB - OBJECTIVE: One of the major damage caused by occlusion in roller pumps is hemolysis. Comparative studies between roller pump with adjustments non occlusive and centrifugal pumps have been made in recent decades in an attempt to develop new products and adjustments that cause fewer traumas to the figurative elements of blood. Usually the roller pumps are adjusted by the static method due to concern variables flow that can occur with non-occlusive settings. Excessive slack in the rollers provoke back flow and can provides errors in the calculation of flow by the rotation of the pump, according to the devices added to the circuit and the systemic resistance of the patient. The objective of this study is to evaluate the back flow caused by two types of roller pumps in blood aspirator and cardiotomy reservoir. METHOD: Back flow visualization was performed in blood aspirator and cardiotomy reservoir. It was tested two different models of roller pumps, adjusted by drop rate and dynamic calibration. The tests were conducted with silicone tubes of 3/8 x 1/16 e 1/2 x 3/32 inches in diameter in water and solution similar to blood. RESULTS: We recorded back flow visually in blood aspirator and in cardiotomy reservoir with their measure of values. The pumps had differences in refluxes measured adjusted by the dynamic calibration method. Pump#2 presents back flow adjusted fully occluded. CONCLUSION: The back flow measured in two models of pump present differences (P <0.008). The results indicate differences in its characteristics caused by the process of manufacturing, design or possible wear. Non-occlusive adjustments may cause variations in flow with the increase of resistance added to the circuit, with difficulty to fix the flow by increasing the rotation. PMID- 20305928 TI - Mitral insufficiency surgery to treat advanced heart failure. AB - Dilated cardiomyopathy is characterized by severe, progressive myocardial dysfunction that is, irreversible. That syndrome leads to cardiac remodeling with augmentation of left ventricle volume and sphericity, dilation of the mitral annulus and dislocation of papillary muscles that pulls up the mitral cords thereby restraining leaflet excursion. These biomechanical modifications generate functional mitral valve regurgitation, a dismal prognostic sign. Mitral valve plasty or replacement was introduced as surgical coadjuvants to conventional medical treatment, with good symptomatic improvement. The long term survival benefit is yet to be demonstrated. PMID- 20305929 TI - Role of exercise training on pulmonary ischemia/reperfusion and inflammatory response. AB - Advances in new technologies associated with improvement of knowledge in medicine have promoted important development in therapeutic and preventive approaches in an attempt to diminish complications following cardiothoracic process involving ischemia/ reperfusion (IR). Nevertheless, postoperative pulmonary injuries remain high and are considered one of the most frequent complications after cardiothoracic surgery. Thus, new strategies with prophylactic actions are crucial in cardiovascular area in an attempt to reduce complications and to improve patient life. It is well documented that exercise training is a non pharmacological tool to prevent and/or treat cardiovascular and endocrine metabolic diseases. The aim of this review was to provide an update of several studies pulmonary IR process and its local and systemic complications and the role of inflammatory response. Furthermore, this review focused on the effects of exercise training on the pulmonary IR as an important strategy to diminish its complications. This review shows that few studies exist regarding the health promoting physical exercise in cardiothoracic surgery and how important is necessary to increase studies in this area. Recently, studies from our laboratory showed beneficial effects of exercise training in experimental model of pulmonary IR. Collectively, data show that physical preconditioning for patients is very important approach to reduce postsurgical complications as well as diminish the time of hospitalization which includes a specialized personal trainer in the health team. Moreover, this preventive strategy might improve patient recovery and would lead to consuming less resources of the health care system. This review included experimental studies in English and Portuguese found in SciELO and MEDLINE (from 1987 to 2008) and also classics texts related to the title. PMID- 20305930 TI - Approach for surgical correction of pulmonary artery coarctation without cardiopulmonary bypass. AB - Pulmonary artery coarctation often happens in patients with pulmonary atresia. The correction has been usually performed using cardiopulmonary bypass and during the neonatal period, influencing pulmonary artery development and prognosis. Three patients with pulmonary atresia with PDA underwent correction using median sternotomy without cardiopulmonary bypass. The PDA maintained the arterial saturation during Blalock Taussig anastomoses upon the contralateral pulmonary artery. Arterioplasty was performed using an autologous pericardium with 7-0 PDS running suture and saturation was maintained by Blalock shunt. All patients presented good follow-up and where discharged with good enlargment of coarctation area. PMID- 20305931 TI - Experience with the posterior leaflet extension technique for correction of rheumatic mitral insufficiency in children. AB - OBJECTIVE: To describe the experience with the technique of posterior leaflet extension in children suffering of rheumatic mitral regurgitation. METHODS: Between April 2002, and October 2007, 30 children, mean age 11.3 years, underwent correction of mitral insufficiency with the technique of posterior leaflet extension with a pericardial patch. Eight also received a Carpentier ring. Six children had aortic valve disease and were submitted to Ross operation (five cases) or valve replacement with an aortic homograft. All were in functional class III or IV (NYHA classification). RESULTS: There was one death. One child presented severe hemolysis in the postoperative period and was submitted to mitral valve replacement. Clinical evolution in the remaining patients was good. CONCLUSIONS: Posterior leaflet extension of the mitral valve seems to be an effective surgical technique for correction of rheumatic mitral insufficiency in children. PMID- 20305932 TI - Pacemaker endocarditis: approach for lead extraction in endocarditis with large vegetations. AB - The presence of large lead vegetations poses additional difficulties for explantation because many methods cannot be used due to the potential hazard of embolism. We report two patients with large vegetation on the ventricular lead due to endocarditis and one of them with an atrial septal defect associated. It was applied a combined technique of transvenous lead removal and sternotomy with cardiopulmonary bypass for the complete removal of pacemaker wires. This procedure resolved the pacemakers endocarditis safely and subsequently a new transvenous device was placed on the opposite site. PMID- 20305933 TI - Late outcome of right ventricular outflow tract repair using bicuspid pulmonary prosthesis in tetralogy of Fallot surgery repair: case report. AB - We present a case of a 19 year-old female patient, with tetralogy of Fallot and hypoplastic pulmonary ring. Diagnosis was performed by echocardiography and cardiac catheterization. The surgical repair was performed at the age of 2 years old. A right ventricular outflow tract remodeling was performed using a porcine pulmonary bicuspid prosthesis. The patient presented a uneventful follow-up during 17 years. Postoperative assessment has shown: mild pulmonary insufficiency and mild pulmonary ventricle gradient, satisfactory right ventricular performance and prosthesis not presenting calcification. This is an option to correct the tetralogy of Fallot adopted by our Institution in the last two decades. PMID- 20305934 TI - An intraoperative transesophageal echocardiography-guided maneuver to assist the removal of an intraventricular thrombus. AB - Intra-cavitary thrombus size, mobility and friability are of great importance in deciding whether surgical removal is indicated. Thrombus characteristics may render surgical thrombectomy incomplete, a risk for catastrophic embolization. During de-airing of the heart, after removal of an intraventricular thrombus, filling the open ventricular cavity with blood serendipitously allowed trans esophageal echocardiographic (TEE) visualization of undetected residual thrombi fragments. This experience leads us to advocate repeated filling and emptying of the left ventricle with blood, under TEE guidance, in order to facilitate complete removal of thrombotic material prior to ventriculotomy closure, and prior to weaning from cardiopulmonary bypass (CPB). PMID- 20305935 TI - Off-pump correction of coronary fistula: the single suture technique approach. AB - The single suture technique was developed to obtain stabilization and exposure of all all coronary branches during off-pump coronary artery bypass, while maintaining hemodynamic stabilily during the procedure. We describe the use of this technique during an off-pump correction of a coronary artery fistula associated with right coronary dilatation. The suggested technique is quicker and less complex than on-pump surgery. Furthermore, it can be a useful tool for congenital fistula correction in select cases, stimulating the practice of less invasive heart surgery in these patients. PMID- 20305936 TI - Jatene's operation without Lecompte maneuver in child with Taussig-Bing heart. PMID- 20305937 TI - Minimally invasive video-assisted atrial septal defect correction and myocardial revascularization. PMID- 20305938 TI - To MCT / CNPq / MEC / CAPES program of editing and publication of Brazilian scientific journals. PMID- 20305941 TI - [Epidemiology of preterm birth: current trends]. PMID- 20305942 TI - [Conjoined twins: an experience of a tertiary hospital in Southeast Brazil]. AB - PURPOSE: to analyze the occurrence of conjoined twins at a tertiary perinatology reference university hospital over a period of 25 years (January 1982 to January 2007) and to describe the successful separation of one of the pairs. METHODS: we consulted retrospectively the database of the University Hospital of the Medical School of Ribeirao Preto, University of Sao Paulo, Brazil, in order to determine the number of pairs of conjoined twins, their frequency, classification, gender, type of pregnancy resolution, attempted surgical separation, prenatal diagnosis and survival. RESULTS: we detected 14 pairs of conjoined twins (1/22,284 live births and 1/90 pairs of twin live births) born during this period (six males, seven females and one of indeterminate sex). The prenatal diagnosis was performed in all twins and all births were accomplished by cesarean section. The separation was possible in only one pair, which survives in excellent health conditions after eight years. Of the remaining 13, ten died on the day of birth and three survived only a few months (less than one year). CONCLUSION: Although our study revealed an abnormally high number of conjoined twins, this is a rare phenomenon, with a poor perinatal prognosis depending on the organs shared by the twins and associated malformations, especially those related to the fetal heart. Due to the poor prognosis of these pairs and to the maternal reproductive impairment caused by the need to perform body cesareans, we suggest that, based on these numbers, early interruption of these pregnancies be legally granted, as in the case of other diseases incompatible with fetal survival outside the uterus. Thus, the confirmation of a diagnosis of conjoined twins and the resolution of pregnancy should be performed at a tertiary obstetric and perinatal care center, and an authorization for the interruption of pregnancy should be obtained by judicial means. PMID- 20305943 TI - [Congenital cardiopathies screening associated with diabetes mellitus using maternal fructosamine plasma concentration]. AB - PURPOSE: to evaluate the importance of maternal plasma concentration of fructosamine as an indicator of fetal congenital cardiopathies in pregnancies complicated by diabetes mellitus. METHODS: this was a retrospective study conducted on 91 pregnant women with diabetes mellitus who underwent routine fetal echocardiography at a university reference center in fetal medicine. Sixty-five patientes who presented pre-gestational diabetes mellitus and plasma fructosamine level were registered in the medical records prior to the ultrasound exam. The first measurement recorded was compared with the result of routine fetal echocardiography, carried out by a specialist physician of the service. The presence or absence of echocardiographic findings of congenital cardiopathies (EFCC) was related to plasma levels of fructosamine by the mean t-test and its accuracy for EFCC was verified by the ROC curve. Plsama fructosamine concentrations of 2.68, 2.9 and 2.23 mmol/L, which are, respectively, the local reference laboratory values, the value of the kit employed for measurement and the one of highest overall accuracy, were discussed as the cut-off values. RESULTS: EFCC was found in 52.3% of the fetuses. The first measurement of fructosamine, during the prenatal care period, was performed, on average, at 20.4+/-8.0 weeks of pregnancy. The maternal concentration ability of the fructosamine to identify fetuses with EFCC was significant (p<0.0001) and had an area under the ROC curve of 0.78 (95%CI=0.66-0.89). The 2.9 mmol/L plasma concentration of fructosamine revealed EFCC with better specificity, but with a higher percentage of false-negative results (96.8 and 55.9%). Values above 2.68 mmol/L were associated with a probability of 4.6 to identify fetuses with EFCC compared with lower values, with 58.8% of sensitivity and 87.1%, specificity. The value of 2.23 mmol/L proved to be the most overall accurate of the three values suggested, with a sensitivity of 88.2% in the identification of fetuses with echocardiographic abnormalities. CONCLUSIONS: it is possible to use a second trimester plasma fructosamine level to refer high risk pregnant women to a reference center of fetal echocardiography. These findings are important for the management of women with diabetes mellitus who initiate late prenatal care. PMID- 20305944 TI - [Sociocultural adaptation of the short personal experiences questionnaire (SPEQ) in Brazil]. AB - PURPOSE: to translate into Brazilian Portuguese and culturally adapt the Short Personal Experiences Questionnaire (SPEQ) to climacteric women. METHODS: the original English version from the University of Melbourne, Australia, was initially translated into Portuguese and back-translated into English. A sociocultural adaptation of vocabulary and linguistic constructions was performed to facilitate comprehension. The questionnaire was then pretested in successive stages in 50 women, until no doubts remained. The final version of the adapted instrument was self-responded by 378 Brazilian-born women, between 40 to 65 years old, with 11 years or more of schooling in a population-based study. The reliability (internal consistency as measured by Cronbach's alpha), the construct validity (correlation coefficients between the items comprising the SPEQ and selected variables) and the criterion validity (correlation coefficient between sexual dysfunction score and overall score of sexual life classification) were analyzed. RESULTS: one hundred and eight women answered all the questions of the SPEQ and were included in the study. Internal consistency (Cronbach's alpha) for all the nine SPEQ items ranged from 0.55 to 0.77 and the general alpha was 0.68. In the construct validity analysis, most of the correlation coefficients were significant (p<0.005). The criterion validity analysis showed significant correlation coefficients in most cases. CONCLUSIONS: following the adaptation process, the Portuguese version of the SPEQ was deemed useful and appropriate for collecting data on sexual function and dyspareunia in Brazilian women, aged 45 to 65 years, with at least 11 years of schooling. PMID- 20305945 TI - [Strategies for reduction of exposure to ionizing radiation in women undergone to uterine fibroid embolization]. AB - PURPOSE: to determine the dose of ionizing radiation absorbed by the ovaries and the skin of patients undergoing uterine fibroid embolization (UFE), and to suggest a radiologic protocol directed at reducing the risks involved in this procedure. METHODS: seventy-three consecutive women (mean age: 27 years) participating in an institutional research protocol, having symptomatic uterine fibroids with indication for minimally invasive treatment, underwent UFE. We estimated the radiation absorbed by the ovaries by means of vaginal dosimeters and the radiation dose absorbed by the skin by means of indirect calculations of radiation absorption. The first 49 patients belonged to the Pre-modification Group, and the last 24, to the Post-modification Group. The second group received a modified protocol of X-ray imaging, with a reduction by half of the frames number per second during arteriography, in an attempt to match the values obtained to those of the literature, and avoiding as much as possible unnecessary exposure to the X-ray beam. RESULTS: there were no technical complications in any of the procedures performed. There were no differences in the mean fluoroscopy time or in the mean number of arteriographies between the two groups. We obtained a 57% reduction in the estimated absorbed ovarian dose between groups (29.0 versus 12.3 cGy) and a 30% reduction in the estimated dose absorbed by the skin (403.6 versus 283.8 cGy). CONCLUSIONS: a significant reduction in the absorption of radiation in patients undergoing UFE can be achieved by changing the number of frames per second in angiographic series, and by the routine use of radiological protection standards. PMID- 20305946 TI - [Clinical and microbiological profile of women with bacterial vaginosis]. AB - PURPOSE: to study the clinical and microbiological profile of women with bacterial vaginosis participating in a randomized, double-blind clinical trial, which compared the vaginal use of preparations from red pepper tree and metronidazole for the treatment of genital discharge. METHODS: the study was conducted on a series of 277 women with bacterial vaginosis concomitantly diagnosed by the criteria of Amsel and Nugent, selected from a total of 462 recruited patients using the information obtained before intervention. Data were analyzed with the Epi-Info 3.32 software. In order to compare the outcomes frequencies between the intervention groups, the chi2 test was used and the risk ratio and 95% confidence interval were calculated. The intention to treat analysis was performed. In addition to the determination of diagnostic parameters, the culture of vaginal content and a Papanicolaou cytology test were also performed. RESULTS: the most frequent clinical complaints were genital discharge, observed in 206 participants (74.4%) and the fish odor of the vaginal secretion, which occurred in 68.6% of the cases (190 patients). Among the diagnostic clinical criteria, the presence of clue-cells was positive in 275 women (99.3%), the Whiff test, in 266 (96.0%), followed by pH >4.5, which occurred in 92.8% of the cases, and by the presence of fluid grayish discharge reported by 206 participants (74.4%). Regarding the Nugent criterion, the median score was 8.0. Culture of the vaginal content permitted the identification of Gardnerella vaginalis in 96.8% of cases and of Mobiluncus in 53.1%. Only one third of the exams showed the presence of Lactobacillus (89 women - 32.1%). Fungal growth occurred in the cultures of 14 participants (5.1%). In most cases, culture revealed the presence of Corynebacterium (94.2%), Gram-positive cocci (98.2%), as well as Gram-positive (99.3%) and Gram-negative (91.0%) bacilli. Oncotic colposcopy revealed a very scarce presence of lactobacilli, which were present in only 8 cytological exams (2.9%) out of the total of 273 exams performed. CONCLUSIONS: the results of the present study did not differ from the literature regarding the symptoms reported by the women, the clinical criteria most frequently observed in the diagnosis, or the bacterial species detected in cultures of vaginal content. These findings indicate the need for further studies that might better elucidate the interrelations between the microbiological findings and the clinical expression of bacterial vaginosis. PMID- 20305947 TI - [Effect of high doses of tibolone in body weight and lipid profile of ovariectomized rats]. AB - PURPOSE: to evaluate the effect of the prolonged use of a high dose of tibolone on the body weight variation and lipid profile of oophorectomized female rats. METHODS: 15 Wistar rats weighing 250 g were randomly divided into two groups. The Experimental Group (n=9) received 1 mg/day of oral tibolone. The Control Group (n=6) received daily 0.5 mL of 0.5% carboxymethylcellulose by gavage. Bilateral oophorectomy was performed 30 days before the beginning of the experiment. On day 0 of the experiment, the animals began to receive the respective treatment for 20 weeks. Body weight was controlled every seven days and food consumption was measured every three to four days along the experiment, in order to establish the daily mean consumption per animal. The results were compared by the Student's t test, with the significance level set at p<0.05. RESULTS: the daily food consumption of the Tibolone Group was significantly lower (12.7+/-1.2 g, p<0.001) compared to the Control Group (14.5+/-1.4 g). This difference was also significant when the body weight was compared between the Tibolone and Control Groups (p<0.001), with the Tibolone Group having lower weight along the experiment. At the end of the experiment, the mean body weight was 215.6+/-9.3 g in the Tibolone Group and 243.6+/-6.4 g in the Control Group. Regarding the lipid profile, the Tibolone Group had significantly (p<0.001) lower total cholesterol compared to the Control Group (30.3 versus 78.6 mg/dL). The level of HDL-c was also significantly different (p<0.001), with the Tibolone Group showing lower levels than the Control Group (9.0 versus 52.0 mg/dL). No significant difference between the groups was registered in the other biochemical parameters examined (LDL-c, VLDL-c and triglycerides). CONCLUSIONS: tibolone causes a significant reduction of HDL-c and total cholesterol and has a deleterious effect on the body weight of oophorectomized rats, which may be related to the lower food ingestion by these animals. PMID- 20305948 TI - Antiviral activity of the green marine alga Ulva fasciata on the replication of human metapneumovirus. AB - We evaluated the antiviral activity of the marine alga, Ulva fasciata, collected from Rasa beach and Forno beach, Buzios, Rio de Janeiro, Brazil on the replication of human metapneumovirus (HMPV). The algae extracts were prepared using three different methodologies to compare the activity of different groups of chemical composites obtained through these different methodologies. Four out of the six extracts inhibited nearly 100% of viral replication. The results demonstrated that the majority of the extracts (five out of six) possess virucidal activity and therefore have the ability to interact with the extracellular viral particles and prevent the infection. On the other hand, only two extracts (from Forno beach, obtained by maceration and maceration of the decoction) were able to interact with cell receptors, hindering the viral entry. Finally, only the extract of algae collected at Forno beach, obtained by maceration presented intracellular activity. To our knowledge, this is a pioneer study on antiviral activity of marine algae against HMPV. It is also the first on antiviral activity against HMPV ever done in Brazil. The study also shows the effect of different environment factors and different chemical procedures used to obtain the extract on its biological properties. PMID- 20305949 TI - Circulation of antibodies against yellow fever virus in a simian population in the area of Porto Primavera Hydroelectric Plant, Sao Paulo, Brazil. AB - Yellow fever (YF) is an acute viral infectious disease transmitted by mosquitoes which occurs in two distinct epidemiological cycles: sylvatic and urban. In the sylvatic cycle, the virus is maintained by monkey's infection and transovarian transmission in vectors. Surveillance of non-human primates is required for the detection of viral circulation during epizootics, and for the identification of unaffected or transition areas. An ELISA (enzyme-linked immunosorbent assay) was standardized for estimation of the prevalence of IgG antibodies against yellow fever virus in monkey sera (Alouatta caraya) from the reservoir area of Porto Primavera Hydroelectric Plant, in the state of Sao Paulo, Brazil. A total of 570 monkey sera samples were tested and none was reactive to antibodies against yellow fever virus. The results corroborate the epidemiology of yellow fever in the area. Even though it is considered a transition area, there were no reports to date of epizootics or yellow fever outbreaks in humans. Also, entomological investigations did not detect the presence of vectors of this arbovirus infection. ELISA proved to be fast, sensitive, an adequate assay, and an instrument for active search in the epidemiological surveillance of yellow fever allowing the implementation of prevention actions, even before the occurrence of epizootics. PMID- 20305950 TI - Preliminary investigation of Culicidae species in South Pantanal, Brazil and their potential importance in arbovirus transmission. AB - In view of the high circulation of migratory birds and the environmental and climatic conditions which favor the proliferation of arthropods, the Brazilian Pantanal is susceptible to circulation of arboviruses. However, the amount of data concerning arbovirus vectors in this area is scarce; therefore the aim of this study was to conduct a preliminary investigation of Culicidae species in the Nhecolandia Sub-region of South Pantanal, Brazil and their potential importance in the arbovirus transmission. A total of 3684 specimens of mosquitoes were captured, 1689 of which caught in the rainy season of 2007, were divided into 78 pools and submitted to viral isolation, Semi-Nested RT-PCR and Nested RT-PCR, with a view to identifying the most important arboviruses in Brazil. Simultaneously, 70 specimens of ticks found blood-feeding on horses were also submitted to the same virological assays. No virus was isolated and viral nucleic acid detection by RT-PCR was also negative. Nevertheless, a total of 22 Culicidae species were identified, ten of which had previously been reported as vectors of important arboviruses. The diversity of species found blood-feeding on human and horse hosts together with the arboviruses circulation previously reported suggest that the Nhecolandia Sub-region of South Pantanal is an important area for arbovirus surveillance in Brazil. PMID- 20305952 TI - Seroprevalence of human toxocariasis in Andean communities from the Northeast of Lima, Peru. AB - The aim of this study was to assess the seroprevalence of human toxocariasis in three Andean communities from the Northeast of Lima, Peru. A total of 303 subjects including children and adults were studied and blood samples were collected to detect anti-Toxocara antibodies by ELISA-IgG test and by hematological examination; stool samples were collected also for parasitological examination. The overall seroprevalence of toxocariasis observed in the total population was 20.46%, with a significant high proportion in children from one to 10 years old (p = 0.034). Among the subjects with positive serology, 32.26% of them had respiratory disturbances, 22.58% hepatomegaly, 17.74% ocular signs or symptoms, 14.51% abdominal pain, 9.68% neurological involvement, and 4.84% cutaneous signs, but none of these clinical features were associated to a positive serology by multivariate analysis. Furthermore, 79.03% of seropositive subjects also harbored at least one intestinal parasite, which was associated to a positive serology (p < 0.05). The presence of pets within the houses, a previous history of pica or geophagia and the use of public places were also present in this population, but only the latter was associated to the serology (p < 0.05). In conclusion, clinical, serological, and epidemiological evidences for larval Toxocara infection were found in the studied population. PMID- 20305951 TI - Characterization of a Hepatitis B virus strain in southwestern Parana, Brazil, presenting mutations previously associated with anti-HBs Resistance. AB - The present study investigated if hepatitis B virus (HBV) mutants circulate in the southwestern region of the State of Parana, Brazil, by analyzing samples from children who received immunoprophylaxis but were born to HBV carrier mothers. Samples from 25 children were screened for HBV serum markers and for HBV DNA by PCR. Only one sample was positive for HBsAg, anti-HBs and HBV DNA, although the child had been vaccinated. Analysis of the S gene sequence of this sample showed the presence of a proline at position 105, a serine at position 114, three threonines at positions 115, 116 and 140, and a glutamine at position 129. The presence of these amino acids, except for serine at position 114, has been related to monoclonal or polyclonal therapy with anti-HBs after liver transplantation, whereas the presence of threonine at position 116 has been described in immunized children from Singapore. This finding demonstrates the possible circulation of HBV strains resistant to hepatitis B immunoprophylaxis in southwestern Parana, Brazil. The genotype of the sample was identified as genotype D, which is frequently found in the region studied. Since 36% of the children had received incomplete or no immunoprophylaxis, more extensive follow up of children born to HBsAg-positive mothers is needed. PMID- 20305953 TI - Human toxocariasis: a seroepidemiological survey in the Amazonian city of Yurimaguas, Peru. AB - The aim of this study was to determine the seroprevalence of the infection by Toxocara in the general population of the Amazonian city of Yurimaguas, Peru. From March to August 2008, a total of 300 subjects were sampled and tested by means of a Toxocara ELISA-IgG test. A clinical and epidemiological questionnaire was used to assess the symptomatology and risk factors associated with human toxocariasis. The overall rate of seropositivity was 35.66%, with a significant high proportion in children (p < 0.001). The clinical evaluation revealed that 95.33% of the seropositive group had some type of symptomatology: headache (66.36%), respiratory compromise (63.55%), abdominal pain (54.21%), cutaneous signs (40.19%) and ocular manifestations (36.45%), and almost all of them were statistically significant (p < 0.001). Furthermore, 56.07% of the seropositive subjects presented at least one intestinal pathogen parasite with predominance of helminthes, but without significant association (p = 0.334). The analysis of risk factors showed only that the use of public places and geophagia exhibited a significant association with the seropositivity (p < 0.001). Clinical, serological and epidemiological findings associated to infection with Toxocara were observed in the present study and future studies should be done to assess this serious health problem. PMID- 20305954 TI - Modulatory activity of antioxidants against the toxicity of Rifampicin in vivo. AB - The World Health Organization (WHO) has shown concern about the burden of tuberculosis in the developing countries. Even though rifampicin is an effective drug in the management of tuberculosis, it has been documented to have some toxic effects in humans. Therefore, this study intends to investigate the modulatory effect of vitamins C and E on the hepatotoxicity, sperm quality and brain toxicity of Rifampicin. Forty Wistar albino rats were used, 10 animals per group. Group 1 animals received 0.3 mL of distilled water, the Group 2 animals received the therapeutic dose of rifampicin, Group 3 animals received therapeutic doses of rifampicin plus vitamin E, while Group 4 received therapeutic doses of rifampicin and vitamin C. The administration was performed orally during three months; the animals were sacrificed by cervical dislocation at the end of that period. Blood samples were collected and liver function and lipid profile was analyzed using fully automated clinical chemistry device. The liver, brain and reproductive organs underwent histopathological examination. Sperm samples were collected from the epididymis to achieve count and motility and morphological analysis. Results showed rifampicin alone to raise (p < 0.05) liver function enzymes (Aspartate amino transferase [AST], Serum alanine amino transferase [ALT] and Total Bilirubin) when compared with controls. While the vitamin E treated group showed remarkable protection, the vitamin C treated group showed questionable protection against the rifampicin induced liver damage. Sperm count results showed an important (p < 0.05) increase in the sperm quality in vitamin E and C treated groups. However, the vitamin E plus Rifampicin treated group showed increased lipid peroxidation. The histopathological findings revealed structural damages by rifampicin in liver, brain and epididymis while some remarkable architectural integrity was observed in the antioxidant-treated groups. It can be concluded that vitamin E or C improved sperm quality and protected against the brain damage caused by rifampicin. Moreover, vitamin E demonstrated remarkable hepatoprotection against rifampicin induced damage while vitamin C shows a questionable hepatoprotection. PMID- 20305955 TI - Skin lesions in envenoming by cnidarians (Portuguese man-of-war and jellyfish): etiology and severity of accidents on the Brazilian coast. AB - This work attempts to establish dermatological identification patterns for Brazilian cnidarian species and a probable correlation with envenoming severity. In an observational prospective study, one hundred and twenty-eight patients from the North Coast region of Sao Paulo State, Brazil were seen between 2002 and 2008. About 80% of these showed only local effects (erythema, edema, and pain) with small, less than 20 cm, oval or round skin marks and impressions from small tentacles. Approximately 20% of the victims had long, more than 20 cm, linear and crossed marks with frequent systemic phenomena, such as malaise, vomiting, dyspnea, and tachycardia. The former is compatible with the common hydromedusa from Southeast and Southern Brazil (Olindias sambaquiensis). The long linear marks with intense pain and systemic phenomena are compatible with envenoming by the box jellyfish Tamoya haplonema and Chiropsalmus quadrumanus and the hydrozoan Portuguese man-of-war (Physalis physalis). There was an association between skin marks and probable accident etiology. This simple observation rule can be indicative of severity, as the Cubozoa Class (box jellyfish) and Portuguese man of-war cause the most severe accidents. In such cases, medical attention, including intensive care, is important, as the systemic manifestations can be associated with death. PMID- 20305956 TI - Clinical and epidemiological study of 27 poisonings caused by ingesting puffer fish (Tetrodontidae) in the states of Santa Catarina and Bahia, Brazil. AB - Puffer fish can be poisonous due to the presence of the potent neurotoxins such as Tetrodotoxin (TTX) and Saxitoxin (STX) found in its tissues. The authors report 27 human poisonings from ingestion of puffer fish in patients treated at Toxicology Centers in the states of Santa Catarina and Bahia, Brazil, between 1984 and January 2009. Poisonings were classified as moderate (52%) and severe (33%), two deaths were observed. Early diagnosis is very important to ensure respiratory support. PMID- 20305957 TI - Hepatitis C virus genotypes in hemodialysis patients in the Federal District, Brazil. AB - Hepatitis C virus (HCV) genotypes and subtypes were determined in hemodialysis patients in the Federal District, Brazil, by sequencing of the 5' noncoding (NC) and nonstructural 5B (NS5B) regions. From 761 patients, 66 anti-HCV-positive samples were tested for HCV RNA. All 51 HCV RNA-positive samples by PCR of the 5' NC region were genotyped as genotypes 1 (90.2%) and 3 (9.8%). Subtype 1a (82.3%) was the most prevalent, followed by subtypes 3a (9.8%), 1b (5.9%) and 1a/1b (2.0%). Forty-two samples could be amplified and genotyped in the NS5B region: 38 (90.5%) as genotype 1, subtypes 1a, and 8 (9.5%) as genotype 3, subtype 3a. For the 42 samples sequenced in both regions, the genotypes and subtypes determined were concordant in 100% and 95.2% of cases, respectively. Two samples presented discrepant results, with the 5' NC region not distinguishing correctly the subtypes 1a and 1b. These findings indicate that the HCV genotype 1, subtype 1a, is the most prevalent among hemodialysis patients in the Federal District, Brazil. PMID- 20305958 TI - Evaluation of the histopathological hepatic lesions and opportunistic agents in Brazilian HIV patients. AB - INTRODUCTION: to evaluated the type histopathological hepatic lesions and opportunistic agents in Brazilian HIV-infected patients. METHODS: we examined 52 percutaneous liver biopsies of 50 HIV-infected patients who had at least two of the following conditions: fever of unknown origin, unexplained severe emaciation, hepatomegaly or abnormal liver chemistry. The specimens were cultured for mycobacteria and fungi and stained by standard procedures. RESULTS: reactive patterns, granulomatous hepatitis and chronic active hepatitis were verified in 28 (54%), 11 (21%) and 8 (15%) of the patients respectively. Opportunistic infections were diagnosed in 18 (36%) patients: mycobacteria in 12 (24%), Cryptococcus neoformans in 5 (10%) patients and mycobacteria and yeast was isolated from the same liver fragment in one patient. CONCLUSIONS: mycobacteriosis was the most common opportunistic infection and liver tissue culture is an important method to detect opportunistic agents, even in the absence of histological lesions. PMID- 20305959 TI - Human papillomavirus genotypes in asymptomatic young women from public schools in Rio de Janeiro, Brazil. AB - INTRODUCTION: The aim of this work was to survey HPV information from a random population of young women from Rio de Janeiro, Brazil. METHODS: This cross sectional study included cervical samples from 241 female students. To determine human papillomavirus status, polymerase chain reaction amplification was performed. HPV typing was determined by restriction fragment length polymorphism analysis. Demographic data, life style, sexual and gynecological history were obtained through use of a structured questionnaire. RESULTS: The average age of the women was 19.6 years-old (SD=3.4 years). HPV prevalence was 27.4%. Nineteen different HPV genotypes were detected, including 13 high risk types. HPV 16 was the most prevalent type (6.2%), followed by 31 (4.1 %) and 66 (3.7%). Most of the oncogenic types belonged to the A9 species (28/48). The frequency of women infected by at least one oncogenic type was significantly higher than those only infected by low risk types (18.7% versus 7.5%). Cervical changes were detected in 12.5% of the sample and were significantly linked to infection with HPV types of the A9 species. Demographic variables, sexual initiation, or number of sexual partners were not associated with HPV prevalence, variety of HPV genotypes or oncogenic types. CONCLUSIONS: The relative frequency of HPV genotypes other than vaccine types in young females should be taken into account when evaluating vaccination strategies. Due to the high prevalence of HPV infection among the population studied, implementation of sex education in schools, promotion of condom use and an organized screening program to prevent cervical cancer must be encouraged for this age group. PMID- 20305960 TI - Occurrence of positivity for Trypanosoma cruzi in triatomine from municipalities in Southeastern Brazil, from 2002 to 2004. AB - INTRODUCTION: from an epidemiological point of view, more than 120 species of triatomine (Hemiptera, Reduviidae) are known. The occurrence and positivity for Trypanosoma cruzi in triatomines in 16 municipalities of the Triangulo Mineiro and Alto Paranaiba were evaluated from January 2002 to December 2004. METHODS: the triatomines were captured basically according to the classic norms of the National Health Foundation. The parasitological exams of the triatomines were conducted according to the technique described by the Ministry of Health. During the study period, 990 specimens of triatomines were captured and of these, 771 could be examined. RESULTS: five species were identified: Triatoma sordida, Panstrongylus diasi, Panstrongylus megistus, Panstrongylus geniculatus and Rhodnius neglectus. Triatoma sordida represented 71.5% of all the triatomines captured, followed by Panstrongylus megistus (18%), Rhodnius neglectus (9.3%), Panstrongylus diasi (0.8%) and Panstrongylus geniculatus (0.4%). Of the total number of triatomines examined, 2.7% were positive for Trypanosoma cruzi. Panstrongylus megistus was the species that presented the highest rates of infection by Trypanosoma cruzi (8.3%), followed by Rhodnius neglectus (2.9%) and Triatoma sordida (1.4%). CONCLUSIONS: there is a need to adapt to new circumstances in epidemiology, with greater emphasis on entomological surveillance, since the potential for adaptation of secondary species of triatomines exists, especially where Chagas' disease is already under control. PMID- 20305961 TI - Comparative biology of the two sister species of Triatominae (Hemiptera: Reduviidae). AB - INTRODUCTION: Triatoma pseudomaculata and T. wygodzinskyi (Hemiptera: Reduviidae: Triatominae) are two Brazilian vectors of Chagas disease. The first is an arboricolous species in sylvatic environment and considered a vector of T. cruzi in peridomestic structures; the second, a rupicolous species in the wild environment of no epidemiological importance. In order to test the assumption that sister species share biological traits, comparative studies of their development cycle and blood ingestion were conducted. METHODS: Eggs laid by five field females of each species were randomly selected. The nymphs were observed daily and fed on mice weekly. The time required to pass through the different stages to adulthood was recorded in days. The triatomines were weighed individually before and after feeding. The mortality rate according to each nymphal stage was calculated. RESULTS AND CONCLUSIONS: Analysis of the results shows that they display only minor biological differences even though they exhibit a distinct ecology. This suggests that the biological traits are important criteria to determine the relationship between species. PMID- 20305962 TI - Risk factors for physical disability at diagnosis of 19,283 new cases of leprosy. AB - INTRODUCTION: The purpose of this study was to evaluate risk factors for physical disability at the moment of leprosy diagnosis. METHODS: This is a retrospective, descriptive and exploratory investigation of 19,283 patients with leprosy, registered in the State of Minas Gerais, Brazil, between 2000 and 2005. RESULTS: The risk of Grade 2 disability was 16.5-fold higher in patients with lepromatous leprosy, and 12.8-fold higher in patients presenting the borderline form, compared to patients presenting indeterminate leprosy. The occurrence of more than one thickened nerve increased the odds of a patient developing Grade 2 disability, 8.4-fold. Age <15 years, multibacillary leprosy and no formal education presented 7.0, 5.7 and 5.6 odds of developing physical disability, respectively. CONCLUSIONS: These factors should be considered as strong prognostic indicators in the development of physical disability at diagnosis. PMID- 20305963 TI - [Influence of acute-phase inflammatory response on serum levels of retinol and retinol binding protein in HIV/AIDS patients]. AB - INTRODUCTION: Hyporetinolemia is an independent prognostic factor in AIDS patients. Inflammatory activity causes a reduction in the serum levels of this nutrient in the general population. However, there are no studies assessing the impact of inflammatory activity on the serum retinol level in AIDS patients. METHODS: A cross-sectional assessment was conducted on 41 patients hospitalized due to AIDS complications. Inflammatory markers (C-reactive protein and tumor necrosis factor-alpha) and serum retinol and retinol binding protein concentrations were quantified. RESULTS: Despite the low (14.6%) prevalence of hyporetinolemia, a significant negative correlation was observed between the inflammatory markers and the serum retinol and retinol binding protein levels in AIDS patients. CONCLUSIONS: Acute-phase inflammatory activity is associated with low serum retinol levels in individuals with AIDS. PMID- 20305964 TI - [Clinical and evolutionary characteristics of 134 patients with disseminated histoplasmosis associated with AIDS in the State of Ceara]. AB - INTRODUCTION: Since the beginning of the HIV epidemic in Ceara, disseminated histoplasmosis (DH) has often been detected among AIDS patients. METHODS: In order to investigate the clinical and laboratory characteristics, evolution and survival of cases of DH/AIDS coinfection, the medical records on 134 cases of DH admitted to a reference hospital in Ceara between 1999 and 2005 were analyzed. RESULTS: Patients with DH presented higher frequency of daily fever, coughing, weight loss, enlarged liver and spleen and acute kidney failure. The diagnosis was made using investigation and/or cultures. At admission, the following were risk factors for death among DH patients: vomiting, dyspnea, respiratory failure, acute kidney failure, hemoglobin < or = 8g/l, urea > or = 40mg/dl and creatinine > or = 1.5 mg/dl. CONCLUSIONS: Patients with DH characteristically presented higher fever, previous hospitalization due to respiratory infection and more clinical complications. Significant anemia and elevated urea were independent risk factors for death among DH patients. PMID- 20305965 TI - [Clinical and laboratory profile of children living with vertically transmitted HIV/AIDS in a city in northeastern Brazily]. AB - INTRODUCTION: Vertical transmission constitutes the main route for child infection by the HIV-1 virus (human immune deficiency virus). This study aimed to investigate the clinical and laboratory evolution of children with vertically transmitted HIV/AIDS. METHODS: This was a retrospective descriptive study based on data gathered from the medical records of all the children who were seen at a specialized care unit between January 1998 and June 2006. RESULTS: Eighty children who met the inclusion criteria were evaluated. In the cases 56 (70%) of the children, their mothers were diagnosed as HIV-positive after childbirth. The delivery was vaginal for 44 (55%) of the children. Fifty-six children (70%) were breastfed by their mothers for periods ranging from one to more than 12 months. Failure to use or incomplete use of the ACTG 076 protocol was documented in 63 (78.5%) of the cases. CONCLUSIONS: The findings from our study are a cause for considerable concern and show failures of medical care for mothers and children, particularly with regard to prevention of transmission. PMID- 20305966 TI - [Ophthalmological evaluation of patients with AIDS and neurotoxoplasmosis]. AB - INTRODUCTION: To describe fundoscopic findings among patients with AIDS and active-phase neurotoxoplasmosis. METHODS: A prospective study of case series type was developed, including 70 patients of both sexes and ages ranging from 20 to 63 years who were admitted to the wards of three public hospitals in the city of Recife, Pernambuco, Brazil, from January to October 2008, with diagnoses of AIDS and neurotoxoplasmosis determined according to the criteria of the Centers for Disease Control and Prevention (1992). The patients were characterized by a first episode of neurotoxoplasmosis (65; 92.9%) or recurrence (5; 7.1%), unawareness of having AIDS (23; 32.9%), mean T CD4+ count of 139.8 + or - 3.04 lymphocytes/mm(3) and mean viral load of 137,080 + or - 39,380 copies/ml. All patients underwent ophthalmological examination consisting of ocular inspection, gauging of visual acuity, investigation of ocular extrinsic muscle function and fundoscopy using a binocular indirect ophthalmoscope (model OHM 3.5 Eyetec) and external lens of 20 diopters (Volk). RESULTS: The findings consisted of retinal cotton-wool spot exudates (8.6%), slight diffuse arteriolar constriction (8.6%), retinochoroiditis scars characteristic of ocular toxoplasmosis (5.7%), atrophy of retinal pigment epithelium (2.9%), retinal detachment (2.9%), increased papillary excavation (1.4%), retinal peripheral degeneration (1,4%), macroaneurysm (1.4%), bilateral papilledema (1.4%) and vitreous-retinal traction (1.4%). CONCLUSIONS: Patients with AIDS and neurotoxoplasmosis may present fundoscopic abnormalities characteristic of ocular toxoplasmosis, either in active or in scar form, related to HIV or even to other opportunist or systemic diseases, which can be of great aid for integral treatment of patients by a multiprofessional team. PMID- 20305967 TI - [Prevalence of anti-Leishmania spp antibodies in dogs from Garanhuns, in the middle scrub zone (Agreste) of Pernambuco]. AB - INTRODUCTION: Considering the unknown situation regarding canine visceral leishmaniasis in Garanhuns, this study had the aim of investigating occurrences of anti-Leishmania spp antibodies in domesticated and partially domesticated dogs, and the possible risk factors involved. METHODS: In the first phase of the study, 256 blood samples were collected from dogs and subjected to the indirect fluorescent antibody test (IFAT) reaction at a dilution of 1:40. Additionally, 23 IFAT-positive samples were tested using an immunochromatographic dipstick test. In the second phase, new blood samples were collected from 18 dogs that were IFAT positive in the first phase. These animals were retested using IFAT (1:40 and 1:80) and, additionally, by means of the polymerase chain reaction to investigate the Leishmania infantum DNA. Furthermore, 16 of these samples were retested using the immunochromatographic dipstick test. RESULTS: In the first phase of the study, 16% of the samples were IFAT-positive (1:40) and only three (13%) were positive in the immunochromatographic dipstick test. In the second phase, 12 samples were IFAT-positive at the dilution of 1:40, and seven were also positive at 1:80. None of the samples were positive in the polymerase chain reaction testing or in the immunochromatographic dipstick test. Clinical signs suggestive of visceral leishmaniasis were observed in 4.9% of the IFAT-positive dogs. There were no statistical differences in relation to age, sex or clinical status of the dogs, but there was a difference in relation to place of origin. CONCLUSIONS: The domesticated and partially domesticated dogs living in Garanhuns present anti Leishmania spp antibodies, but are mostly asymptomatic. PMID- 20305968 TI - [Factors relating to occurrences of cutaneous leishmaniasis in the Ribeira Valley]. AB - INTRODUCTION: This study aimed to identify the environmental and social factors that determined occurrences of American cutaneous leishmaniasis in the Ribeira valley region of the State of Sao Paulo between 1998 and 2006. METHODS: Secondary public-domain data from the 23 municipalities forming this region were used. The study period was divided into three ranges based on the graphical characteristics of the incidence coefficients. These data were subjected to analysis using multiple linear regression. RESULTS: Over the period 1998 to 2000, the variables correlated with American cutaneous leishmaniasis were mean human development index (p = 0.007), per capita income (p = 0.390) and degree of urbanization (p = 0.079). Over the periods 2001 to 2003 and 2004 to 2006, the variables correlated with American cutaneous leishmaniasis were the presence of sandflies (p = 0.000; p = 0.001) and mean urban population (p = 0.007; p = 0.001). CONCLUSIONS: These data show the trend towards urbanization and impoverishment of the disease. PMID- 20305969 TI - [Autochthonous malaria notified in the State of Sao Paulo: clinical and epidemiological characteristics from 1980 to 2007]. AB - INTRODUCTION: Autochthonous malaria in the State of Sao Paulo is characterized by sporadic outbreaks in the western region and by persistent transmission in the eastern region, where oligosymptomatic cases with low parasitemia due to Plasmodium vivax occur. The objectives of this study were to assess the completeness of autochthonous malaria notification forms; to estimate the incidence trends of autochthonous cases in the State of Sao Paulo from 1980 to 2007; and to analyze the clinical and epidemiological patterns of cases in two autochthonous regions over this period. METHODS: This was a descriptive study that analyzed 18 variables on the notification form for malaria in the State of Sao Paulo, comparing these two regions over two periods (1980-1993 and 1994 2007). The data sources were SUCEN/SES/SP, SINAN/CVE/SES/SP and DATASUS. RESULTS: The completeness was greater than 85% for 11 variables. The incidence trend was decreasing. There were 821 autochthonous cases: 91.6% occurred in the eastern region, predominantly due to Plasmodium vivax. Asymptomatic infection had a higher percentage in the second period (p < 0.001). CONCLUSIONS: The completeness of the information was satisfactory. The clinical differences observed deserve attention from epidemiological surveillance agencies, which need to deal with the challenge of asymptomatic infection by Plasmodium. PMID- 20305970 TI - [Cross-sectional study on toxoplasmosis among female students on a university course in the Presidente Prudente region, State of Sao Paulo]. AB - INTRODUCTION: Toxoplasmosis is a parasitic disease caused by the protozoan Toxoplasma gondii, which affects humans and other animals. The most severe form is congenital toxoplasmosis. Thus, it is important to establish the serological profile of women before pregnancy. This study aimed to analyze the serology of toxoplasmosis among female students on the nursing course at Unoeste (Universidade do Oeste Paulista), in Presidente Prudente, SP. METHODS: Blood samples were collected from 80 female students aged 18 to 35 years after they had signed the consent statement. Occurrences of anti-Toxoplasma gondii IgM and IgG antibodies were determined using the ELISA method. This study was approved by the institution's ethics committee and was conducted in the Immunology Laboratory at Unoeste. RESULTS: Among the 80 blood samples analyzed, 27 female students were positive for IgG, whereas none of them were positive for IgM antibodies. CONCLUSIONS: Among the 80 female students, 53 (66.2%) would be susceptible to toxoplasmosis in a possible pregnancy. Twenty-seven of the female students (33.8%) were considered seropositive. PMID- 20305971 TI - [Epidemiological profile of leprosy in a Brazilian municipality between 2000 and 2006]. AB - INTRODUCTION: Leprosy is considered to be a major public health problem in developing countries. It is estimated that notifications are issued only in relation to 1/3 of the patients and that, among these patients, many undergo irregular treatment or drop out, thus increasing the impact of the disease. The objective this paper was to describe the epidemiological profile of the population with a diagnosis of leprosy in the municipality of Uberaba, State of Minas Gerais, Brazil, between 2000 and 2006. METHODS: This was a retrospective study using data from notifications of leprosy cases in the Notifiable Disease Information System of the Brazilian Ministry of Health. RESULTS: There were 455 recorded cases of leprosy, and 55.4% of these were among males. The most affected age group was 34 to 49 years (31.4%), while nine cases of leprosy (2%) were found in children under the age of 15 years. The commonest clinical form was the borderline type (69.1%) and the operational class was multibacillary (87%). These findings are a matter of concern, considering that the age group that is most economically active is potentially the principal group spreading the disease. CONCLUSIONS: The finding that 87% of the cases were multibacillary indicates that the diagnoses were late. It is therefore necessary to decentralize the leprosy care services and train more professionals to enable earlier diagnosis and treatment. PMID- 20305972 TI - [Prescription patterns and antibiotic use in community-based infections]. AB - INTRODUCTION: The aim of this study was to find out about the patterns of antibiotic use in the municipality of Sorocaba, through evaluating the reported diagnosis and the therapy used. METHODS: An evaluation tool was applied among antibiotic users over a 12-month period. Sociodemographic data and information relating to health, diagnosis and therapeutics were gathered in relation to 403 users. RESULTS: Great present use and the greatest previous use was found in the 0-10 year-old age group (p < 0.05). Infections with lung involvement were the ones most mentioned (p < 0.05) and penicillins were the drugs most used, present in 45.1% of the prescriptions. The mean duration of therapy for otitis (8.9 days) was below the recommendation. For sinusitis, 22% of the prescriptions did not give guidance regarding recommended use (10 days). CONCLUSIONS: The lack and/or nonuse of therapeutic protocols resulted in great differences in prescription patterns, thereby leading to therapeutic failure and recurrence of infections, which were situations frequently found in this study. PMID- 20305973 TI - [Spatial distribution and breeding site characteristics of Aedes albopictus and Aedes aegypti in Fortaleza, State of Ceara]. AB - INTRODUCTION: Since the registration of Aedes albopictus in the municipality of Fortaleza in 2005, it has shown rapid dispersion. A study aiming to identify its occurrence areas, breeding sites and associations with Aedes aegypti and other culicids was carried out during 2008. METHODS: Between January and July 2008, samples of immature forms of culicids were gathered from properties located in districts of Fortaleza. Certain features of the breeding sites were highlighted, such as location (indoors or outdoors), presence of covering (protection against impact of sunlight and rain), water turbidity (water clear or not clear), constituent material, volume, height above ground level and simultaneous presence of different species of culicids in the same breeding site. RESULTS: Indoor location was an important factor for the breeding sites for Aedes albopictus [PR = 0.52; 95% CI: 0.33-0.81]. On the other hand, water turbidity and reservoir covering were not shown to be differentiators regarding infestation [p > 0.05]. Absence of water turbidity was significant for Aedes aegypti infestation in breeding sites [PR = 1.14; 95% CI: 1.06-1.22]. CONCLUSIONS: Absence of one of the species from the breeding sites enhanced the infestation by another species. Breeding sites that had not been infested by Aedes albopictus had a prevalence of infestation by Aedes aegypti that was 2.05 times greater [95% CI: 1.72-2.44]. There was no significant association between volume and height of the breeding sites and infestation by both species. Both species were found to be dispersed throughout the municipality, occupying a wide diversity of breeding sites. However, a slight physical separation could be identified, with higher infestation with Aedes albopictus outdoors. PMID- 20305974 TI - [Phlebotomine fauna (Diptera: Psychodidae) in a campina reserve in the State of Amazonas, and its epidemiological importance]. AB - INTRODUCTION: In Brazil, the largest diversity of phlebotomines is found in the Amazon region, particularly in undisturbed terra-firma forest. However, the phlebotomine fauna in other ecosystems of this region is still not well known. METHODS: In order to investigate the phlebotomine fauna of another Amazon ecosystem, collections were made using CDC light traps in the campina/campinarana ecosystems in the periurban zone of the city of Manaus. RESULTS: Eight hundred and fourteen phlebotomines of 26 species were captured, of which the most abundant were: Lutzomyia flaviscutellata (64.5%); Lutzomyia georgii (14%); Lutzomyia olmeca nociva (8.1%); Lutzomyia furcata (3.2%); Lutzomyia monstruosa (1.3%); Lutzomyia umbratilis (1.1%); and others (7.8%). CONCLUSIONS: The campina/campinarana ecosystems showed great epidemiological importance because of the high abundance of Lutzomyia flaviscutellata and Lutzomyia olmeca nociva, which are both vectors of Leishmania (Leishmania) amazonensis. Based on this information, it will be possible to outline goals for parasitological studies and raise awareness among researchers and students who are constantly exposed in these areas while conducting research work, regarding the possible risk of contamination by Leishmania. PMID- 20305975 TI - [Stingrays in rivers in southeastern Brazil: occurrence localities and impact on the population]. AB - INTRODUCTION: In this paper, our aim was to describe the process of colonization of the upper Parana basin, southeastern Brazil, by stingrays, showing the current situation, likely trend and impact caused and discussing some management actions and mitigation measures. METHODS: Interviews were held with riverbank people and health professionals, to gather information on occurrences of stingrays and accidents associated with these animals, along with underwater observations and collection of specimens, between 2004 and 2009 in localities in the States of Sao Paulo, Parana and Mato Grosso do Sul, in the southeastern, southern and part of the central-western regions of Brazil. RESULTS: Three species of stingrays were identified in the study area, thus demonstrating that they were using the paths opened by the Tiete-Parana Waterway to disperse. Sixteen victims of accidents involving these animals were found, mainly bathers and fishermen. Attention was drawn to the fact that these cases had not been reported, yet they presented high morbidity with notable temporary incapacity for work. CONCLUSIONS: This is the first report on biological invasion involving species of elasmobranchs in the literature and, because stingrays are colonizing densely populated areas and are expanding their range of distribution each year, it can be expected that their negative interactions with humans will intensify, with important changes in the epidemiological profile of accidents due to venomous animals occurring in southeastern Brazil. PMID- 20305976 TI - [Chronic inflammatory demyelinating polyneuropathy after treatment with pegylated interferon alpha 2b in a patient with HIV/HCV coinfection: case report]. AB - Chronic inflammatory demyelinating polyneuropathy has a strong association with HIV and HCV infection. A rare association between chronic inflammatory demyelinating polyneuropathy and hepatitis C treatment with pegylated interferon alpha was described recently. We described the first case of chronic inflammatory demyelinating polyneuropathy associated with pegylated interferon alpha 2b in a white man infected with HIV and HCV. The patient recovered completely with the use of intravenous hyperimmune immunoglobulin. Infectologists and hepatologists should be alert regarding this rare and serious association, which requires immediately drug discontinuation and early treatment. PMID- 20305977 TI - [Fatal poisoning caused by puffer fish (Tetrodontidae): report of a case involving a child]. AB - A case of poisoning resulting from ingestion of viscera from a spotted puffer fish (Sphoeroides testudineus) by a two-year-old child is described. The child presented cold sweating, progressive muscle weakness, cardiorespiratory arrest and death. The risks of consuming the meat and viscera of puffer fish, which is a common occurrence in certain regions of Brazil, are discussed. PMID- 20305978 TI - [Pulmonary adiaspiromycosis treated without antifungal drugs]. AB - The case of a 40-year-old agricultural worker affected by pulmonary adiaspiromycosis is reported. An etiological diagnosis had been established by means of a biopsy via thoracoscopy. Treatment with corticosteroids without antifungal drugs was chosen, and the patient responded well to this, with improvements in clinical and radiological conditions three weeks after the beginning of the symptoms. PMID- 20305979 TI - [Report on an autochthonous case of canine visceral leishmaniasis in the southern zone of the municipality of Rio de Janeiro]. AB - Brazil is facing expansion and urbanization of American visceral leishmaniasis, with human and canine cases in several large-sized cities. This report describes an autochthonous case of canine visceral leishmaniasis in a nonendemic area in the municipality of Rio de Janeiro. PMID- 20305980 TI - PCR-RFLP of 16S ribosomal DNA to confirm the identification of Enterococcus gallinarum and Enterococcus casseliflavus isolated from clinical and food samples. AB - INTRODUCTION: This study aimed to confirm the identification of Enterococcus gallinarum and Enterococcus casseliflavus isolated from clinical and food samples by PCR-RFLP. METHODS: Fifty-two strains identified by conventional biochemical exams were submitted to PCR amplification and digested with HinfI. Only 20 (38.5%) of the 52 strains showed a DNA pattern expected for E. gallinarum and E. casseliflavus. RESULTS: Analysis of the results of this study showed that E. gallinarum and E. casseliflavus are occasionally erroneously identified and confirmed the potential application of 16S rDNA analysis for accurate identification of these species. CONCLUSIONS: A correct identification is important to distinguish between intrinsic and acquired vancomycin resistance. PMID- 20305981 TI - [Destruction of Toxocara canis eggs by the nematophagous fungus Pochonia chlamydosporia]. AB - INTRODUCTION: Toxocara canis is an ascarid parasite of the small intestine of dogs that causes visceral larva migrans in humans. METHODS: With the aim of demonstrating the effectiveness of the fungus Pochonia chlamydosporia on Toxocara canis eggs under laboratory conditions, a trial was set up in Petri dishes with 2% agar-water. RESULTS: There was ovicidal activity of 43.8% (p < 0.01) in the treated group in relation to the control group over the periods studied. CONCLUSIONS: The results from the present study suggest that Pochonia chlamydosporia can potentially be used as an alternative biological control for embryonated Toxocara canis eggs. PMID- 20305982 TI - The first recorded occurrence of Psammolestes coreodes Bergroth, 1911 (Hemiptera: Reduviidae: Triatominae) in the State of Mato Grosso do Sul, Brazil. PMID- 20305983 TI - Schistosoma mansoni eggs in the sperm after total vasectomy. PMID- 20305984 TI - In and out--biochemical and biophysical mechanisms of viral fusion and assembly. PMID- 20305985 TI - Could cells from your nose fix your heart? Transplantation of olfactory stem cells in a rat model of cardiac infarction. AB - This study examines the hypothesis that multipotent olfactory mucosal stem cells could provide a basis for the development of autologous cell transplant therapy for the treatment of heart attack. In humans, these cells are easily obtained by simple biopsy. Neural stem cells from the olfactory mucosa are multipotent, with the capacity to differentiate into developmental fates other than neurons and glia, with evidence of cardiomyocyte differentiation in vitro and after transplantation into the chick embryo. Olfactory stem cells were grown from rat olfactory mucosa. These cells are propagated as neurosphere cultures, similar to other neural stem cells. Olfactory neurospheres were grown in vitro, dissociated into single cell suspensions, and transplanted into the infarcted hearts of congeneic rats. Transplanted cells were genetically engineered to express green fluorescent protein (GFP) in order to allow them to be identified after transplantation. Functional assessment was attempted using echocardiography in three groups of rats: control, unoperated; infarct only; infarcted and transplanted. Transplantation of neurosphere-derived cells from adult rat olfactory mucosa appeared to restore heart rate with other trends towards improvement in other measures of ventricular function indicated. Importantly, donor-derived cells engrafted in the transplanted cardiac ventricle and expressed cardiac contractile proteins. PMID- 20305986 TI - Saliva: physiology and diagnostic potential in health and disease. AB - Saliva has been described as the mirror of the body. In a world of soaring healthcare costs and an environment where rapid diagnosis may be critical to a positive patient outcome, saliva is emerging as a viable alternative to blood sampling. In this review, we discuss the composition and various physiological roles of saliva in the oral cavity, including soft tissue protection, antimicrobial activities, and oral tissue repair. We then explore saliva as a diagnostic marker of local oral disease and focus particularly on oral cancers. The cancer theme continues when we focus on systemic disease diagnosis from salivary biomarkers. Communicable disease is the focus of the next section where we review the literature relating to the direct and indirect detection of pathogenic infections from human saliva. Finally, we discuss hormones involved in appetite regulation and whether saliva is a viable alternative to blood in order to monitor hormones that are involved in satiety. PMID- 20305987 TI - Hepatocyte growth factor in synaptic plasticity and Alzheimer's disease. AB - The hepatocyte growth factor (HGF) was initially identified as a protein that promoted growth of hepatocytes. It regulates proliferation and survival of different types of cells. HGF signaling, which is initiated by its binding to a receptor tyrosine kinase, plays critical roles during development. HGF and its receptor are also present in brain cells. This review describes the role of HGF in hippocampal neurons, synaptic plasticity, and the memory impairment condition, Alzheimer's disease. PMID- 20305988 TI - Corticosteroid regulation of synaptic plasticity in the hippocampus. AB - Stress, via release of steroid hormones, has been shown to affect several cellular functions in the brain, including synaptic receptors and ion channels. As such, corticosteroids were reported to modulate plasticity, expressed as long term changes in reactivity to afferent stimulation. The classical view of the effects of stress on synaptic plasticity and cognitive functions assumes an inverted U-shape curve, such that a low stress level facilitates and a high stress level (i.e., corticosterone levels) impairs cognitive functions. This universal view has been challenged recently in a series of studies that show that stress and corticosterone have immediate and opposite effects on the ability to express long-term potentiation (LTP) in the dorsal and ventral sectors of the hippocampus. This differential role of stress may be related to the different functions associated with these sectors of the hippocampus. Herein, we review the known effects of stress hormones on cellular functions and outline the role of molecular mechanisms in stress-related global functions of the hippocampus. PMID- 20305989 TI - Regenerative medicine for neurological disorders. AB - The annual meeting of the American Society for Neural Therapy and Repair (ASNTR) has always introduced us to top-notch and up-to-date approaches for regenerative medicine related to neuroscience, ranging from stem cell-based therapy to novel drugs. The 16th ASNTR meeting focused on a variety of different topics, including the unknown pathogenesis or mechanisms of specific neurodegenerative diseases, stem cell biology, and development of novel alternative medicines or devices. Newly developed stem cells, such as amniotic epithelial stem cells and induced pluripotent stem cells, as well as well-known traditional stem cells, such as neural, embryonic, bone marrow mesenchymal, and human umbilical cord blood derived stem cells, were reported. A number of commercialized stem cells were also covered at this meeting. Fetal neural tissues, such as ventral mesencephalon, striatum, and Schwann cells, were investigated for neurodegenerative diseases or spinal cord injury. A number of studies focused on novel methods for drug monitoring or graft tracking, and combination therapy with stem cells and medicine, such as cytokines or trophic factors. Finally, the National Institutes of Health guidelines for human stem cell research, clinical trials of commercialized stem cells without larger animal testing, and prohibition of medical tourism were big controversial issues that led to heated discussion. PMID- 20305991 TI - Ten-year trends in dietary intake, health status and mortality rates in free living elderly people. AB - OBJECTIVE: To explore the trends of food preferences and nutrient intake over a 10-year follow-up in a group of successfully aging elderly. DESIGN: Longitudinal study. SETTING: City of Padua, Italy. PARTICIPANTS: Randomly stratified sample of 97 men and 94 women born between 1913 and 1918. MEASUREMENTS: The study involved a dietary assessment conducted in 1988/89 and repeated in 1999. Data were collected by means of a modified validated dietary history. RESULTS: Nutrient and energy intake remained fairly stable over a decade, despite changes in eating habits, with a higher intake of sweets and a lower consumption of soft drinks in both genders. All individuals significantly increased their daily intake of water. CONCLUSION: Despite changes in eating habits, no significant decline in total energy and macronutrient intake was recorded in a decade in our elderly. The increased daily consumption of water and decreased use of soft drinks would suggest that these people were still receptive to nutritional advice even in very old age, while the increase in their sweet-eating might be because aging itself increases a person's sweet tooth, and this could be regarded as an age-related effect on dietary habits. PMID- 20305990 TI - Fever. AB - Measurement of body temperature remains one of the most common ways to assess health. An increase in temperature above what is considered to be a normal value is inevitably regarded as a sure sign of disease and referred to with one simple word: fever. In this review, we summarize how research on fever allowed the identification of the exogenous and endogenous molecules and pathways mediating the fever response. We also show how temperature elevation is common to different pathologies and how the molecular components of the fever-generation pathway represent drug targets for antipyretics, such as acetylsalicylic acid, the first "blockbuster drug". We also show how fever research provided new insights into temperature and energy homeostasis, and into treatment of infection and inflammation. PMID- 20305992 TI - The use of calf circumference measurement as an anthropometric tool to monitor nutritional status in elderly inpatients. AB - OBJECTIVE: The objective of this study was to identify the nutritional status of hospitalized elderly and verify if calf circumference can be a tool to monitor nutritional status in this population. METHODS: A total of 170 inpatients (79 men and 91 women) aged more than 60 years were assessed. Anthropometric and dietary assessments were done according to standard procedures. The software STATISTICA 6.0 was used for the statistical analysis. The confidence interval was set at 95% and significance level at 5% (p < 0.05). RESULTS: Body mass index assessment revealed a high rate of underweight patients (45.3%), and arm circumference and triceps skinfold revealed a high prevalence of depletion. Males had more lean mass according to the mid-arm muscle circumference (p=0.017) and mid-arm muscle area (p=0.01), and females presented higher triceps skinfold values (p < 0.001). There was a positive correlation between calf circumference and Body Mass Index (p < 0.001), arm circumference (p=0.001), triceps skinfold (p=0.001), mid-arm muscle circumference (p=0.001), and mid-arm muscle area (p=0.001). CONCLUSION: This study found a positive correlation between calf circumference and nutritional status of assessed patients indicating that this measurement can be used as a complementary tool for monitoring the nutritional status of elderly inpatients. PMID- 20305993 TI - Exploring cut-off values for large waist circumference in older adults: a new methodological approach. AB - BACKGROUND: There is an ongoing debate about the applicability of current criteria for large waist circumference (WC) in older adults. OBJECTIVES: Our aim was to explore cut-off values for large WC in adults aged 70 years and older, using previously used and new methods. DESIGN: Prospective cohort study. PARTICIPANTS: Data of 1049 participants of the Longitudinal Aging Study Amsterdam (LASA) (1995-1996), aged 70-88y, were used. MEASUREMENTS: Measured BMI and WC, and self-reported mobility limitations. RESULTS: Linear regression analyses showed that the values of WC corresponding to BMI of 25kg/m2 and 30kg/m2 were higher than the current cut-offs. Cut-offs found in men were 97 and 110cm, whereas 88 and 98cm represented the cut-offs in women. Areas under the Receiver Operating Characteristic (ROC) curves showed that the accuracy to predict mobility limitations improved when the higher cut-offs were applied. Spline regression curves showed that the relationship of WC with mobility limitations was U-shaped in men, while in women, the risk for mobility limitations increased gradually with increasing WC. However, at the level of current cut-off values for WC the odds for mobility limitations were not increased. CONCLUSION: Based on results of extensive analyses, this study suggests that the cut-offs for large WC should be higher when applied to older adults. The association of WC with other negative health outcomes needs to be investigated to establish the final cut points. PMID- 20305994 TI - Comparison of two frailty measures in the Conselice Study of Brain Ageing. AB - OBJECTIVES: Uncertainty about the definition of frailty is reflected by the development of many ways to identify frail people. We aimed to compare the validity of two frailty measures in participants of the Conselice Study of Brain Aging. DESIGN: Prospective population-based study with 4 year follow up. PARTICIPANTS/SETTING: 1,016 subjects aged 65 and over in a rural Italian population. METHODS: For each participant, a Frailty Index (FI) and a Conselice Study of Brain Aging Score (CSBAS) were determined. The FI was created from 43 deficits according to a standardized methodology; 7 variables derived from a previously validated Easy Prognostic Score comprised the CSBAS. RESULTS: The FI had characteristic properties described in other population samples, with a gamma distribution, a 99% limit of about 0.64 and higher values in women than men. CSBAS and FI were strongly correlated with each other (r = 0.72) and both correlated with age (r = 0.32, r = 0.27, respectively). Each was independently predictive of death in a multivariate model, with greater specificity and sensitivity than age alone. CONCLUSIONS: Frailty can be measured by different tools and facilitates a more direct quantification of individual vulnerability than chronological age alone. Though the Frailty Index and the Conselice Study of Brain Aging Score are underpinned by different rationales, clinical utility will continue to motivate their development. PMID- 20305995 TI - Short-term influence of elevation of plasma homocysteine levels on cognitive function in young healthy adults. AB - BACKGROUND: Acute homocysteine elevation has been shown to have a significant impact on cognitive function in animal models. OBJECTIVES: Investigation of the short-term impact of elevation of plasma homocysteine levels through a dietary intervention on cognitive abilities of young healthy adults. PARTICIPANTS: 100 healthy medical students of both genders were enrolled in the study. DESIGN AND MEASUREMENTS: Homocysteine levels and cognitive abilities were measured at 08:30 (before breakfast) and at 15:00 (two hours after lunch and six hours after breakfast). Food intake was restricted to specified comestibles. The cognitive assessment comprised a version of the Short Test for General Intelligence, three subtests of the Syndrome Short Test and the Stroop test. RESULTS: At 15:00 plasma homocysteine was significantly elevated in 56 participants (P < 0.00001), whilst in 44 it was decreased (P < 0.00001) in comparison to baseline (08:30). The decrease was however of limited clinical significance. The differences in the changes in cognitive performance between the two groups did not attain statistical significance (P > 0.05) and the direction of the changes did not differ between them. Accordingly, the multiple linear regression analysis did not reveal an important influence of homocysteine elevation on cognitive performance variations. CONCLUSIONS: Significant increase of plasma homocysteine is not associated with a straightforward inhibitory or facilitatory short-term effect on physiological cognitive parameters in young healthy adults. PMID- 20305997 TI - Early Alzheimer's trials: new developments. PMID- 20305996 TI - Predictive factors of hospitalizations in Alzheimer's disease: a two-year prospective study in 686 patients of the REAL.FR study. AB - BACKGROUND: During the course of the Alzheimer's disease (AD), many patients need to be hospitalized either due to the direct consequences of the disease itself, or due to associated diseases or life event. The objective of the present study was to determine predictive factors for hospitalisation in AD patients. METHODS: Six hundred eighty-six AD patients from the French Network on AD (REAL-FR) were follow up and assessed every 6 months for 2 years. During follow-up, all events occurring between two visits, in particular hospital admissions were carefully recorded. RESULTS: Annual incidences for hospitalizations were 26.13% (95% CI, 22.52 to 29.74). After two years, 202 subjects were hospitalized for 296 hospitalizations. Three variables were found to be significant predictors of hospitalisations in the multivariate regression model: dependency for ADL (RR=0.81; 95% CI: 0.70-0.95, p=0.0091), the drug use (use of four or more drugs) (RR=1.83; 95% CI: 1.31-2.58, p=0.0005) and the NPI score (RR=1.011; 95% CI: 1.001 1.022, p=0.0427). For hospitalizations due to the direct consequences of the disease itself, three variables were found to be significant predictors of hospitalisations: dependency for ADL (RR=0.69; 95% CI: 0.53-0.88, p=0.0033), the caregiver burden Zarit score (RR=1.03; 95% CI: 1.01-1.05, p=0.0079) and the NPI score (RR=1.07; 95% CI: 1.03-1.12, p=0.0007). CONCLUSIONS: Intervention to support patients and caregivers to manage loss of ADL may be a practical approach to reduce hospitalisation. Prevention of drug use or optimal treatment of associated diseases in AD seem to be also a challenge to decrease the rates of hospitalization or readmission, and the costs of providing care. PMID- 20305998 TI - Pre-dementia Alzheimer's trials: overview. AB - A series of negative clinical trials of disease-modifying agents for Alzheimer's disease has increased pessimism regarding the prospects for important therapeutic advances. But limited efficacy may be attributed in part to the advanced degree of neurodegeneration present at the onset of dementia. To optimize the likelihood of success, it is essential to develop the methodology to allow testing of disease-modifying treatments at an early stage of pathology, when modulation of pathophysiologic mechanisms may yield major clinical benefits. PMID- 20305999 TI - The potential and limits for clinical trials for early Alzheimer's disease and some recommendations. AB - Recommendations for clinical trials methods for 'pre-dementia,' 'prodromal,' or early Alzheimer's disease are discussed. Early AD can be considered as subsets of both 'amnestic MCI' and 'probable AD.' In principle, it can be operationalized using recently proposed, new research criteria for AD that specifically does not require impairment in non-memory cognitive function and activities of daily living, and consequently does not require the presence of dementia. The criteria also require patients to show abnormal putative biomarkers but require validation. Trials in early AD should be done when models of drug action and response suggest that the drug in development likely would be effective in early AD and clinical effects could be expected in a relatively short time. Biomarkers should be used as stratification or explanatory variables that may help to explain clinical outcomes from early AD trials rather than as inclusion/exclusion criteria in order to avoid pseudospecificity. Trials should be multicentered, double-blinded, randomized, placebo-controlled, generally with dose-ranging of two doses if indicated. Duration of trials should be based on expected onsets and durations of effects, and generally should be less than one year. Crossover trials should be considered when appropriate. Primary outcomes should specifically assess memory and include repeated assessments. Potential secondary outcomes could include self- and observer-rated health-related quality of life and global impressions of change in lieu of activities of daily living. Onset of dementia should not be an endpoint because many patients would be on the cusp of dementia and dementia onset is influenced by numerous biological and environmental factors. Inferences that can be made from trials results will likely involve the effects of the test drug on memory and self-rated global function. Disease modification is not likely to be inferred except in trials over two years in duration in which a change in a biomarker can be used as an adjunctive assessment. Models and simulations using existing clinical trials databases would be helpful in planning early AD trials. PMID- 20306000 TI - Evolving early (pre-dementia) Alzheimer's disease trials: suit the outcomes to the population and study design. AB - Assuming that some cases of Alzheimer's disease (AD) could be prevented or delayed, prevention trials will be developed for this neurodegenerative condition. Initially, stakeholders will have to agree about the definition of prevention-true primary prevention, meaning the prevention of AD neuropathological changes; the prevention of clinical signs and symptoms that often augur AD; or preventing the progression of signs and symptoms to full-blown dementia. True primary prevention trials will have to rely completely upon neuroimaging or biomarker outcomes that reflect AD pathology. On the other hand, trials designed to prevent signs and symptoms of dementia will require researchers to agree on the phenomenology that would constitute an unequivocal endpoint: cognitive worsening on one or more measure compared to a normative group; development of Mild cognitive impairment (MCI); or development of Alzheimer's dementia. Prevention trials utilizing any of these outcomes in the general public will be large, will have to utilize low risk public health interventions, and might therefore have only a small impact (treatment effect size), especially if the studies are too short or the study populations are too diverse. An alternative to interventions aimed at the general public would be any attempt to prevent signs and symptoms of dementia in individuals thought to be at an increased risk for clinical dementia. These trials could try to reduce the development of signs and symptoms of dementia in cognitively normal subjects, or they could try to prevent progression from some form of Mild Cognitive Impairment to AD, or they could have the more subtle goal of reducing the accumulation of subclinical deficits in MCI subjects. If the populations for these trials are limited to individuals who have abnormal laboratory and neuroimaging studies associated with AD neuropathology, the results will not generalize to biomarker negative, at risk individuals, who are likely to constitute the majority of any clinically relevant study population. Outcome measures for each study design will depend upon the characteristics of the study. PMID- 20306001 TI - Clinical trials for early (pre-dementia) Alzheimer's disease: a case for mild cognitive impairment. AB - A goal of many clinical trials for Alzheimer's disease is to develop disease modifying therapies for the pre-dementia period of the Alzheimer's disease process. However, there are no clinical criteria for characterizing subjects in this range. The construct of amnestic mild cognitive impairment has been extensively investigated and may provide useful clinical criteria for this clinical stage. It is proposed that the clinical criteria for mild cognitive impairment be enriched with imaging and other biomarkers to improve the specificity of the outcome, and these criteria might suffice for pre-dementia clinical trials. PMID- 20306002 TI - Seeing with new eyes: finding a path to early intervention trials in Alzheimer's disease. AB - The clinical course of Alzheimer's Disease (AD) and other degenerative disorders affecting cognition can be visualized as a progression from normal cognition through the syndrome of Mild Cognitive Impairment (MCI) to dementia. The use of biomarker data can supplement clinical characterization and identification of MCI and dementia pathologies. Clinical staging algorithms that use both clinical and biomarker information can assist in the early identification of AD patients. A comprehensive outcome measure such as the Clinical Dementia Rating Sum of Boxes (CDR-SB), which has components that assess both cognitive and functional domains in parallel deserves consideration as a primary outcome measure for early AD clinical trials. PMID- 20306003 TI - Dose ranging for trials through biomarkers of drug effects. AB - To test the hypothesis that excess amyloid deposition is an essential step in the pathophysiology of Alzheimer's disease appropriate biomarkers are essential in selecting agents that modify amyloid formation or clearance. Cerebrospinal fluid concentrations of relevant analytes and PET measures of total brain load have been developed. These are directly applied to testing whether drugs reduce various soluble forms of amyloid as well as whether they enhance elimination of material deposited in brain parenchyma. The ideal profile of a drug that can fully test the amyloid hypothesis can be understood in terms of effects on currently available and future biomarkers. Dose selection for clinical trials should require a quantitative threshold effect on the most relevant biomarker. PMID- 20306004 TI - Study design considerations: conducting global clinical trials in early Alzheimer's disease. AB - An increasing number of Alzheimer's disease (AD) clinical trials are being conducted in countries in which such trials have infrequently, if ever, been conducted. The infrastructure for conducting trials in many of these regions is not well developed, leading to particular challenges in collection of biomarkers, which are becoming increasingly important in trials in early AD. Linguistic and cultural differences make scale translation, adaptation, validation and implementation across countries and regions difficult. In addition, multiple translations and versions of scales and differences in their administration increase variability and thus decrease the chance of detecting a signal. These issues are magnified in trials in early AD, where detecting subtle neuropsychological deficits is even more challenging. Two additional significant factors for global AD research include: 1) Differing regulatory authority requirements resulting in the need for repeat studies to satisfy diverse regulatory requirements in different parts of the world; and 2) reimbursement and access may be limited due to different data requirements for country specific economic evaluations. While standardization of biochemical assays and neuroimaging protocols have recently been undertaken, there remains a pressing need for standardization of clinical measures (including translation, linguistic and cultural validation and administration). In addition, a global consensus on regulatory requirements for approval of drugs for the treatment of early AD and identification of universally accepted variables from a cost-effectiveness or value perspective would have significant impact on advancing drug development in early AD. PMID- 20306005 TI - Methodological issues in a cluster-randomized trial to prevent dementia by intensive vascular care. AB - OBJECTIVES: Description of methodological issues in a trial designed to evaluate if a multi-component intervention aimed at vascular risk factors can prevent dementia. DESIGN, SETTING AND PARTICIPANTS: Multi-center, open, cluster randomized controlled clinical trial (preDIVA) including 3535 non-demented subjects aged 70-78, executed in primary practice and coordinated from one academic hospital. General practices are randomized to standard care or intensive vascular care. INTERVENTION: Vascular care consists of 4-monthly visits to a practice nurse who monitors all cardiovascular risk factors. Hypertension, hypercholesterolemia, overweight, lack of physical exercise and diabetes are strictly controlled according to a protocol and treated in a way, tailored to the characteristics of individual participants. MEASUREMENTS: Primary outcomes are incident dementia and disability; secondary outcomes are mortality, vascular events (stroke, myocardial infarction, peripheral vascular disease), cognitive decline and depression. RESULTS: Between May 2006 and February 2009, 3535 subjects from 115 general practices have been included. The clusters have an average size of 31 (SD 22, range 2-114). 1658 Patients from 52 practices were randomized to the standard care condition and 1877 patients in 63 practices to the vascular care condition. DISCUSSION: When designing a cluster-randomized trial, clustering of patient data within GP practices leads to a loss of power. This should be adjusted for in the power calculation. Since intensive vascular care will probably lead to a reduction in cardiovascular mortality, the competing risks of mortality and dementia should be taken into account. PMID- 20306006 TI - Does chair type influence outcome in the timed "Up and Go" test in older persons? AB - OBJECTIVE: To test the effects of the use of a collapsible, portable chair (chair B), as opposed to a 'standard' chair (chair A), on the outcome of the timed "Up and Go" (TUG) test. DESIGN: Cross-sectional. SETTING: Multipurpose senior centres. PARTICIPANTS: Mobile older persons (N=118, mean age 77 years (range 62 99 years)). OUTCOME MEASURES: Time to complete the timed "Up and Go" test using chair A and chair B, and inter-rater agreement in the time scores. RESULTS: Time taken to complete the TUG test did not differ by chair type [median (interquartile range, IQR) = 12.3 (9.53-15.9) and 12.6 (9.7-16.6)] seconds for Chair A and B respectively, p-value=0.87. In multiple regression analyses, factors that impacted on time difference in test performance for the two chairs were use of a walking aid during the test [Odds ratio (OR) = 3.7 95%CI 1.1-11.9, p=0.031], observed difficulty with mobility (OR= 27.7 95%CI 2.6-290, p=0.006), and a history of arthritis in the knees (OR= 2.9 95%CI 1.0-8.7, P=0.05). In an inter-rater agreement analysis, no significant difference was found between time scores recorded by the two raters; median (IQR) = 12.4 (10.9-15.9) and 12.3 (7.2 59.1) seconds for the occupation therapist and for the research assistant, respectively (Wilcoxon matched pairs test, p=0.124, Spearman correlation coefficient = 0.99, p < 0.001). CONCLUSION: The use of a portable canvas chair with standardised specifications offers an acceptable alternative to the use of a 'standard' chair in assessments of fall risk using the TUG test in field settings where field workers are reliant on public transport. PMID- 20306007 TI - Which generic health related Quality of Life questionnaire should be used in older inpatients: comparison of the Duke Health Profile and the MOS Short-Form SF 36? AB - OBJECTIVES: The objective of our study was to compare advantages and limitations of two generic Quality of Life questionnaires administered in older inpatients. DESIGN: Two validated generic health-related Quality of Life instruments : the MOS Short-Form 36 (9 dimensions, 36 items) and the Duke Health Profile (6 dimensions, 4 dysfunctions, 17 items) were administered to inpatients over 65 years. SETTING AND PARTICIPANTS: The sample was drawn from the CliniQualVie program that assessed systematically Quality of Life among hospitalized inpatients (18-79 years) in 10 medical and surgical wards at Nancy University Hospital. RESULTS: The two self-administered questionnaires were completed by 701 patients over 65 years at admission (mean age 71 +/- 4, 63% men). The proportion of patients who completed all items were 72.5% for the Duke and 66.9% for the SF 36 (p < .001). The Duke's internal consistency was low as compared with the SF 36, but other psychometric properties were comparable. Good correlations (Spearman) were observed between the two questionnaires for physical health (0.59, p < .0001), mental health (0.68, p < .0001) and health perception (0.56, p < .0001) scores. Low correlations were observed for the social score. CONCLUSIONS: This is the first study to our knowledge to assess the interest of using the Duke Health Profile in a general elderly inpatients population as compared with the SF-36 questionnaire. Although these two questionnaires have four comparable dimensions, they differ in their content and psychometric properties. The Duke questionnaire, due to its better completion rate and despite some psychometric limitations may be useful in this population, particularly in the more frail patients. PMID- 20306008 TI - Zinc intake and the risk of hyperglycemia among Chinese adults: the prospective Jiangsu Nutrition Study (JIN). AB - OBJECTIVE: To prospectively examine the associations between zinc intake, the zinc to heme iron ratio and the incidence of hyperglycemia in Chinese. METHODS: We followed 1056 healthy adults aged 20 and older from 2002 to 2007. Dietary data were collected using 3-day food record and food frequency questionnaire. Hyperglycemia was defined as fasting plasma glucose > 5.6 mmol/l. RESULTS: During the 5 years of follow-up, we documented 125 incident cases of hyperglycemia. Zinc intake alone was not associated with the risk of hyperglycemia. The zinc to heme iron ratio was inversely associated with the risk of hyperglycemia: odds ratios (OR, 95% CI) across increasing quartiles of the zinc to heme iron ratio were 1.00, 0.78(0.44-1.37), 0.40(0.19-0.83), and 0.21(0.08-0.54)(p for trend= 0.001). Adjustment for lifestyle covariates did not significantly change the associations. CONCLUSIONS: This cohort study suggests that the zinc to heme iron intake ratio was significantly associated with a decreased risk of hyperglycemia in Chinese adults. PMID- 20306009 TI - [The problematic implant]. PMID- 20306010 TI - [Impact of clinical trials for surgery]. AB - Clinical trials play a key role in patient care, academic education and research in surgery. Without valid studies the practice of evidence-based medicine is limited. Surgery is supported through funding by the German Ministry of Education and Research to establish an infrastructure for clinical trials. So far seven universities have worked together in a network since 2007 and successfully obtained funding for six large randomized trials from a program existing since 2004. Until now 2,249 patients have been randomized within 11 trials and 910 patients have been treated at local hospitals without academic responsibilities. An increase in the interest in clinical trials in daily practice has resulted through the certification of hospitals for special treatment that specifies that at least 5% of all patients are included in clinical trials. PMID- 20306011 TI - [NOTES--quo vadis?]. PMID- 20306012 TI - Activation transcription factor-4 and the acute vascular response to injury. AB - Atherosclerosis is a complex fibroproliferative-inflammatory process triggered by vascular injury. Transcription factors play an important role in the control of genes that effect critical changes in the vessel wall. Recent evidence indicates an emerging role for activation transcription factor 4 (ATF4), a master regulator for evolutionarily conserved mammalian stress response pathways, in cardiovascular pathologic settings. For example, in endothelial cells, ATF4 is induced by atherogenic factors such as oxidised phospholipids and homocysteine, and in monocytes, ATF4 is activated by hypoxia. In this context, ATF4 is thought to regulate pro-inflammatory signalling cascades and subsequent apoptosis. ATF4 is induced in aortic smooth muscle cells by fibroblast growth factor 2 and in the intact vessel wall following balloon angioplasty. Our own work indicates that ATF4 knockdown blocks injury-inducible intimal proliferation. Furthermore, studies in ATF4-deficient mice have established a role for ATF4 in diet-induced diabetes and hyperlipidaemia. In this article, we will review recent developments on the regulation of this intriguing nuclear protein and its transcriptional roles in the context of vascular injury and related disease. PMID- 20306014 TI - [Osteoporosis]. PMID- 20306013 TI - Incidence of hospitalised schizophrenia in Finland since 1980: decreasing and increasing again. AB - BACKGROUND: It is suggested that the incidence of schizophrenia is decreasing. However, changes in the number of psychiatric beds available and diagnostic practice have not always been taken into account. We studied the annual first admission rate (per 100,000) for schizophrenia (FARsch) during a rapid deinstitutionalisation period in Finland. METHOD: From the National Finnish Hospital discharge register, we identified all 30,041, 15- to 64-year-old patients admitted for the first time with schizophrenia to hospitals in Finland between 1980 and 2003. RESULTS: FARsch decreased from 56.39 in 1980 to 29.51 in 1991 and slightly increased thereafter. Changes in FARsch corresponded with changes in all admissions. FARsch was higher when using ICD-8, but lower when DSM IIIR and ICD-10 were used. CONCLUSION: Changes in the number of psychiatric beds available, admission policy and diagnostic practice may explain the majority of variations in FARsch. Possibly, increased use of illegal drugs and improved treatment of depression are reflected in the increase in FARsch. PMID- 20306015 TI - Characterizing the risk profiles of intensive care units. AB - OBJECTIVE: To develop a new method to evaluate the performance of individual ICUs through the calculation and visualisation of risk profiles. METHODS: The study included 102,561 patients consecutively admitted to 77 ICUs in Austria. We customized the function which predicts hospital mortality (using SAPS II) for each ICU. We then compared the risks of hospital mortality resulting from this function with the risks which would be obtained using the original function. The derived risk ratio was then plotted together with point-wise confidence intervals in order to visualise the individual risk profile of each ICU over the whole spectrum of expected hospital mortality. MAIN MEASUREMENTS AND RESULTS: We calculated risk profiles for all ICUs in the ASDI data set according to the proposed method. We show examples how the clinical performance of ICUs may depend on the severity of illness of their patients. Both the distribution of the Hosmer Lemeshow goodness-of-fit test statistics and the histogram of the corresponding P values demonstrated a good fit of the individual risk models. CONCLUSIONS: Our risk profile model makes it possible to evaluate ICUs on the basis of the specific risk for patients to die compared to a reference sample over the whole spectrum of hospital mortality. Thus, ICUs at different levels of severity of illness can be directly compared, giving a clear advantage over the use of the conventional single point estimate of the overall observed-to-expected mortality ratio. PMID- 20306016 TI - Surgical anatomy of the foot and ankle. PMID- 20306017 TI - Effects of whole body vibration on bone mineral density and falls: results of the randomized controlled ELVIS study with postmenopausal women. AB - We determined whether the effect of exercise on bone mineral density (BMD) and falls can be enhanced by whole body vibration (WBV). In summary, the multi purpose exercise training was effective to increase lumbar BMD but added WBV did not enhance this effect. However, falls were lowest in the exercise program combined with WBV. INTRODUCTION: WBV is a new approach to reduce the risk of osteoporotic fractures. In the "Erlangen Longitudinal Vibration Study" (ELVIS), we investigated whether WBV enhances the effect of multifunctional exercise on BMD and falls. METHODS: One hundred fifty-one postmenopausal women (68.5 +/- 3.1 years) were randomly assigned to a: (1) conventional training group (TG); (2) conventional training group including vibration (TGV); and (3) wellness control group (CG). TG conducted an exercise program consisting of 20 min dancing aerobics, 5 min balance training, 20 min functional gymnastics, and 15 min dynamic leg-strength training on vibration plates (without vibration) twice a week. TGV performed an identical exercise regimen with vibration (25-35 Hz) during the leg-strengthening sequence. CG performed a low-intensity wellness program. BMD was measured at the hip and lumbar spine at baseline and follow-up using the DXA method. Falls were recorded daily via the calendar method. RESULTS: After 18 months, an increase in BMD at the lumbar spine was observed in both training groups (TGV: +1.5% vs. TG: +2.1%). The difference between the TG and the CG (1.7%) was significant. At the hip no changes were determined in either group. The fall frequency was significantly lower in TGV (0.7 falls/person) compared with CG (1.5), whereas the difference between TG (0.96) and CG was not significant. CONCLUSIONS: A multifunctional training program had a positive impact on lumbar BMD. The application of vibration did not enhance these effects. However, only the training including WBV affected the number of falls significantly. PMID- 20306018 TI - Associations of fat mass and fat distribution with bone mineral density in pre- and postmenopausal Chinese women. AB - Fat mass (FM) is closely related to bone mineral density (BMD). However, the associations of FM and fat distribution with BMD in pre- and postmenopausal women are still poorly understood. The present study showed android fat mass accumulation after menopause had a negative association with BMD. INTRODUCTION: FM is closely related to BMD. However, it is unknown whether FM and central fat distribution have different associations with BMD in pre- and postmenopausal women. The study aims to investigate the associations of FM and fat distribution with BMD in pre- and postmenopausal Chinese women. METHODS: Two hundred sixty premenopausal and 267 postmenopausal women aged 18 to 79 years were analyzed. Lean mass (LM), FM, percent body fat (%BF), android FM, gynoid FM, and total and regional BMD were measured using dual-energy X-ray absorptiometry. Fat distribution was assessed by android to gynoid FM ratio (AOI). Multiple regression analysis was performed to examine the associations of BMD with FM, LM, and AOI. RESULTS: FM, %BF, android FM, and AOI were significantly higher, whereas total and regional BMD were significantly lower in postmenopausal women (all r < 0.01). In premenopausal women, FM was positively associated with total and regional BMD (all r < 0.05). AOI had no significant association with BMD. In postmenopausal women, FM was significantly associated with total and regional BMD even additionally adjusting for LM (all r < 0.01). AOI had significantly negative association with total, head, arm, and leg BMD (all r < 0.05). The results remained unchanged when replacing FM with %BF. CONCLUSIONS: There were different associations of FM and fat distribution with BMD in pre- and postmenopausal Chinese women. Increased central body fat had a negative association with BMD. Our findings may have significant implications in the prevention of menopause related osteoporosis through reducing centralized fat deposition. PMID- 20306019 TI - Green tea polyphenols attenuate deterioration of bone microarchitecture in female rats with systemic chronic inflammation. AB - Green tea polyphenols (GTP) are promising agents for preventing bone loss. GTP supplementation sustained microarchitecture and improved bone quality via a decrease in inflammation. Findings suggest a significant role for GTP in skeletal health of patients with chronic inflammation. INTRODUCTION: This study evaluated whether GTP can restore bone microstructure along with a molecular mechanism in rats with chronic inflammation. A 2 [placebo vs. lipopolysaccharide (LPS)]* 2 [no GTP vs. 0.5% GTP (w/v) in drinking water] factorial design was employed. METHODS: Female rats were assigned to four groups: placebo, LPS, placebo + GTP, and LPS + GTP for 12 weeks. Efficacy was evaluated by examining changes in bone microarchitecture using histomorphometric and microcomputed tomographic analyses and by bone strength using the three-point bending test. A possible mechanism was studied by assessing the difference in tumor necrosis factor-alpha (TNF-alpha) expression in tibia using immunohistochemistry. RESULTS: LPS lowered trabecular volume fraction, thickness, and bone formation in proximal tibia while increasing osteoclast number and surface perimeter in proximal tibia and eroded surface in endocortical tibial shafts. GTP increased trabecular volume fraction and number in both femur and tibia and periosteal bone formation rate in tibial shafts while decreasing trabecular separation in proximal tibia and eroded surface in endocortical tibial shafts. There was an interaction between LPS and GTP in trabecular number, separation, bone formation, and osteoclast number in proximal tibia, and trabecular thickness and number in femur. GTP improved the strength of femur, while suppressing TNF-alpha expression in tibia. CONCLUSION: In conclusion, GTP supplementation mitigated deterioration of bone microarchitecture and improved bone integrity in rats with chronic inflammation by suppressing bone erosion and modulating cancellous and endocortical bone compartments, resulting in a larger net bone volume. Such a protective role of GTP may be due to a suppression of TNF-alpha. PMID- 20306020 TI - Using clinical risk factors and bone mineral density to determine who among patients undergoing bone densitometry should have vertebral fracture assessment. AB - SUMMARY: Vertebral fracture assessment (VFA) is a new method for imaging thoracolumbar spine on bone densitometer. Among patients referred for bone densitometry, the selection of patients for VFA testing can be optimized using an index derived from clinical risk factors and bone density measurement. PURPOSE: VFA, a method for imaging thoracolumbar spine on bone densitometer, was developed because vertebral fractures, although common and predictive of future fractures, are often not clinically diagnosed. The study objective was to develop a strategy for selecting patients for VFA. METHODS: A convenience sample from a university hospital bone densitometry center included 892 subjects (795 women) referred for bone mineral density (BMD) testing. We used questionnaires to capture clinical risk factors and dual-energy X-ray absorptiometry to obtain BMD and VFA. RESULTS: Prevalence of vertebral fractures was 18% in women and 31% in men (p = 0.003 for gender difference). In women, age, height loss, glucocorticoid use, history of vertebral and other fractures, and BMD T-score were significantly and independently associated with vertebral fractures. A multivariate model which included above predictors had an area under the receiver operating curve of 0.85 with 95% confidence interval (CI) of 0.81 to 0.89. A risk factor index was derived from the above multivariate model. Using a level of 2 as a cut-off yielded 93% sensitivity (95% CI 87, 96) and 48% specificity (95% CI 69, 83). Assuming a 15% prevalence of vertebral fractures, this cut-off value had a 24% positive and 97% negative predictive value and required VFA scanning of three women at a cost of $60 (assuming a $20 cost/VFA scan) to detect one with vertebral fracture(s). CONCLUSIONS: Selecting patients for VFA can be optimized using an index derived from BMD measurement and easily obtained clinical risk factors. PMID- 20306021 TI - Denosumab-related osteonecrosis of the jaws. PMID- 20306022 TI - Effects of GH-IGF-I excess and gonadal status on bone mineral density and body composition in patients with acromegaly. AB - SUMMARY: Studies on body composition and bone mineral density in acromegaly have conflicting results. Our data point to an increase in lean mass, a decrease in adipose tissue, and that the anabolic effect of GH on bone is partially dependent on modifications in body composition. INTRODUCTION: The effects of growth hormone (GH) and insulin-like growth factor I (IGF-I) excess and gonadal status on bone mineral density (BMD) and body composition (BC) in acromegalic patients are uncertain. METHODS: Bone mineral density and BC were evaluated by dual-energy X ray absorptiometry (Prodigy-GE) in 75 patients (22 men and 53 women) with acromegaly, mean age 48.9 +/- 14.5 years. Acromegaly was considered "controlled" when serum IGF-I was within the specific age-adjusted reference range, and serum GH was lower than 2.5 ng/mL. Comparisons between groups were performed using unpaired t test or Mann-Whitney U test. Categorical variables were analyzed by chi-square (x (2)) test. In order to compare data of different subgroups stratified by disease activity and gonadal status, one-way analysis of variance (ANOVA) and Bonferroni post hoc analysis were performed. To evaluate the correlation between GH and IGF-I and densitometric parameters, Pearson and Spearman rank order correlation were performed, as appropriate. RESULTS: There were no differences in BMD when considering disease activity and gonadal status. Active disease and eugonadism were positively correlated to an increase in lean mass and a decrease in fat mass. After multiple linear regression, there were positive correlations between GH and Z-score at lumbar spine and between lean mass and BMD at proximal femur. CONCLUSION: Our data support that GH-IGF-I excess and eugonadism have great influence on BC modifications and that the anabolic effects of GH-IGF-I on bone are, at least in part, dependent on these alterations in body composition. PMID- 20306023 TI - Association between hyperglycaemia and fracture risk in non-diabetic middle-aged and older Australians: a national, population-based prospective study (AusDiab). AB - SUMMARY: The association between pre-diabetes and fracture risk remains unclear. In this large cohort of middle-aged and older Australian men and women without diabetes, elevated 2-h plasma glucose and pre-diabetes were associated with a reduced 5-year risk of low trauma and all fractures in women, independently of BMI, fasting insulin and other lifestyle factors. INTRODUCTION: We aimed to (1) examine associations between fasting and 2-h plasma glucose (FPG and 2-h PG), fasting insulin and risk of low trauma and all fractures in non-diabetic adults and (2) compare fracture risk between adults with pre-diabetes (impaired glucose tolerance or impaired fasting glucose) and those with normal glucose tolerance (NGT). METHODS: Six thousand two hundred fifty-five non-diabetic men and women aged >=40 years with NGT (n = 4,855) and pre-diabetes (n = 1,400) were followed for 5 years in the AusDiab Study. Fractures were self-reported. RESULTS: Five hundred thirty-nine participants suffered at least one fracture (368 women, 171 men), of which the majority (318) occurred after a low-energy trauma (258 women, 60 men). In women, a 2-h PG >= 7.2 mmol/L (highest quartile) was associated with a decreased risk of low trauma and all fractures independent of age and BMI [OR (95% CI) for low trauma fractures, 0.59 (0.40-0.88)], but also fasting insulin, smoking, physical activity, history of fracture, dietary calcium and alcohol intake or menopausal status. There was no effect of 2-h PG on fracture risk in men [OR (95% CI), 1.39 (0.60-3.26)] or any relationship between fracture risk and quartiles of FPG or insulin in either sex. Compared to women with NGT, those with pre-diabetes had a reduced risk of fracture [OR (95% CI) for all fractures, 0.70 (0.52-0.95); for low trauma fractures, 0.75 (0.53-1.05)]. CONCLUSION: Elevated 2 h PG levels and pre-diabetes were inversely associated with low trauma and/or all fractures in non-diabetic women, independent of BMI and fasting insulin levels. PMID- 20306024 TI - Insight into the evolutionary history of symbiotic genes of Robinia pseudoacacia rhizobia deriving from Poland and Japan. AB - The phylogeny of symbiotic genes of Robinia pseudoacacia (black locust) rhizobia derived from Poland and Japan was studied by comparative sequence analysis of nodA, nodC, nodH, and nifH loci. In phylogenetic trees, black locust symbionts formed a branch of their own suggesting that the spread and maintenance of symbiotic genes within Robinia pseudoacacia rhizobia occurred through vertical transmission. There was 99-100% sequence similarity for nodA genes of Robinia pseudoacacia nodulators, 97-98% for nodC, and 97-100% for nodH and nifH loci. A considerable sequence conservation of sym genes shows that the symbiotic apparatus of Robinia pseudoacacia rhizobia might have evolved under strong host plant constraints. In the nodA and nodC gene phylograms, Robinia pseudoacacia rhizobia grouped with Phaseolus sp. symbionts, although they were not closely related to our isolates based on 16S rRNA genes, and with Mesorhizobium amorphae. nifH gene phylogeny of our isolates followed the evolutionary history of 16S rDNA and Robinia pseudoacacia rhizobia grouped with Mesorhizobium genus species. Nodulation assays revealed that Robinia pseudoacacia rhizobia effectively nodulated their native host and also Amorpha fruticosa and Amorpha californica resulting in a significant enhancement of plant growth. The black locust root nodules are shown to be of indeterminate type. PMID- 20306026 TI - Mechanical stimulation and intermittent parathyroid hormone treatment induce disproportional osteogenic, geometric, and biomechanical effects in growing mouse bone. AB - Mechanical loading and intermittent parathyroid (iPTH) treatment are both osteoanabolic stimuli and are regulated by partially overlapping cellular signaling pathways. iPTH has been shown clinically to be effective in increasing bone mass and reducing fracture risk. Likewise, mechanical stimulation can significantly enhance bone apposition and prevent bone loss, but its clinical effects on fracture susceptibility are less certain. Many of the osteogenic effects of iPTH are localized to biomechanically suboptimal bone surfaces, whereas mechanical loading directs new bone formation to high-stress areas and not to strain-neutral areas. These differences in localization in new tissue, resulting from load-induced versus iPTH-induced bone accumulation, should affect the relation between bone mass and bone strength, or "tissue economy." We investigated the changes in bone mass and strength induced by 6 weeks of mechanical loading and compared them to changes induced by 6 weeks of iPTH treatment. Loading and iPTH both increased ulnar bone accrual, as measured by bone mineral density and content, and fluorochrome-derived bone formation. iPTH induced a significantly greater increase in bone mass than loading, but ulnar bone strength was increased approximately the same amount by both treatments. Mechanical loading during growth can spatially optimize new bone formation to improve structural integrity with a minimal increase in mass, thereby increasing tissue economy, i.e., the amount of strength returned per unit bone mass added. Furthermore, exercise studies in which only small changes in bone mass are detected might be more beneficial to bone health and fracture resistance than has commonly been presumed. PMID- 20306027 TI - The intracellular localization and function of the ATP-sensitive K+ channel subunit Kir6.1. AB - Our aim was to determine the subcellular localization and functional roles of the K(ATP) channel subunit Kir6.1 in intracellular membranes. Specifically, we focused on the potential role of Kir6.1 as a subunit of the mitochondrial ATP sensitive K+ channel. Cell imaging showed that a major proportion of heterologously expressed Kir6.1-GFP and endogenously expressed Kir6.1 was distributed in the endoplasmic reticulum with little in the mitochondria or plasma membrane. We used pharmacological and molecular tools to investigate the functional significance of this distribution. The K(ATP) channel opener diazoxide increased reactive oxygen species production, and glibenclamide abolished this effect. However, in cells lacking Kir6.1 or expressing siRNA or dominant negative constructs of Kir6.1, the same effect was seen. Ca2+ handling was examined in the muscle cell line C2C12. Transfection of the dominant negative constructs of Kir6.1 significantly reduced the amplitude and rate of rise of [Ca2+]( c ) transients elicited by ATP. This study suggests that Kir6.1 is located in the endoplasmic reticulum and plays a role in modifying Ca2+ release from intracellular stores. PMID- 20306028 TI - Seasonal variations of renal colics and urolithiasis: is this the time for a shared benchmark to study the phenomenon? PMID- 20306029 TI - Technical aspects of measurement of cellular electromagnetic activity. AB - Electromagnetic fields generated by living cells have been experimentally investigated in the past 3 decades; however, the results are often inconsistent. In this paper we discuss some technical aspects of such challenging experiments, a brief review of which is also included. Special attention is paid to the sensor with respect to the power available from a cell and the power needed to excite the macroscopic measurement devices. We drew the conclusion that the nanoelectronic approach should be used. PMID- 20306030 TI - Kinetics of stearic acid transfer between human serum albumin and sterically stabilized liposomes. AB - The kinetics of the transfer of stearic acids between human serum albumin (HSA) and long circulating sterically stabilised liposomes (SSL) composed of dipalmitoylphosphatidylcholine (DPPC) and of submicellar content of the polymer lipid poly(ethylene glycol:2000)-dipalmitoylphosphatidylethanolamine (PEG:2000 DPPE) have been studied by fluorescence spectroscopy. The study exploits the fact that HSA has a single tryptophan (Trp) residue and that the intrinsic Trp emission intensity is quenched by the presence of doxyl spin-labelled stearic acids (SASL). Protein/lipid dispersions are considered in which SASL molecules are inserted either in the protein or in the SSL, and the transfer of SASL between the protein and SSL is conveniently monitored by the time variation of the inherent Trp-fluorescence intensity of HSA. It was found that the transfer of fatty acids between HSA and SSL depends on the type of donor and acceptor matrix, on the temperature (i.e., on the physical state of the lipid bilayers) and on the grafting density of the PEG-lipids at the lipid/protein interface. In the absence of polymer-lipids, the rate of transfer increases with temperature in both directions of transfer, and it is higher for the passage from DPPC bilayers to HSA. The presence of polymer-lipids reduces the rate of transfer both in the mushroom and in the brush regime of the polymer chains, especially at low grafting density and for lipid membranes in the fluid phase. PMID- 20306031 TI - Alpha particles more promising than toxins? PMID- 20306032 TI - Clinical and survival impact of FDG PET in patients with suspicion of recurrent cervical carcinoma. AB - PURPOSE: The aim of this retrospective study was to evaluate the contribution of (18)F-FDG PET to the clinical management and survival outcome of patients suspected of recurrent cervical carcinoma and in line with the hypothesis that early diagnosis of recurrent cervical cancer may improve overall survival. METHODS: A total of 40 patients underwent conventional imaging (CI) and FDG PET/CT for suspected cervical cancer. Clinical management decisions were recorded with CI and additional PET/CT. Discordances and concordances between CI and PET/CT results were compared to the final diagnosis as based on histopathology analysis or follow-up considered as the gold standard. RESULTS: The final diagnosis was established pathologically (n = 25) or by median clinical follow-up for 48 months after the PET (n = 15). The PET/CT was positive in 76% (20/26) of patients compared to 19% (6/26) with CI. Globally PET/CT modified the treatment plan in 55% (22/40) of patients and in 75% (18/24) when the CI was negative prior to PET/CT. These changes led to the use of previously unplanned therapeutic procedures in 37.5% (15/40). When FDG PET was positive for recurrence (> 3 foci), the median overall survival was 12 months (2-70) compared to patients with PET findings with < or = 1 focus for which the median survival was not attained (p = 0.007). A multivariate analysis of prognostic factors demonstrated that abnormal FDG uptake (> 3 foci) was the most significant factor (p < 0.03) for death from cervical cancer. CONCLUSION: FDG PET is a valuable tool in the case of suspected recurrence of cervical cancer on account of its impact on treatment planning and especially in predicting patient outcome. PMID- 20306033 TI - Optimizing the colloid particle concentration for improved preoperative and intraoperative image-guided detection of sentinel nodes in prostate cancer. AB - PURPOSE: Lymphatic mapping for prostate cancer can be used to determine therapeutic strategies. Sentinel node visualization requires sufficient nodal tracer uptake. We evaluated the effect of an increase in particle concentration on preoperative and intraoperative sentinel node depiction. METHODS: Enrolled in the study were 50 consecutive patients with prostate cancer. The first 25 patients (group A) received nanocolloid with standard labelling (0.4 ml (99m)Tc per 0.1 mg nanocolloid). The last 25 patients (group B) received nanocolloid with a reduced labelling dilution volume (0.4 ml (99m)Tc per 0.2 mg nanocolloid). The aimed injected volume and dosage were the same for both groups (225 MBq in 0.4 ml). Intratumoral tracer injection was followed by planar lymphoscintigraphy (15 min and 2 h), SPECT/CT and laparoscopic sentinel lymphadenectomy. Lymph node visualization was evaluated using a four-point scoring system (0 nonvisualization to 3 intense visualization) and count quantification on the 2-h anterior lymphoscintigram. In addition to the gamma ray detection probe, a portable gamma camera was used for intraoperative sentinel node visualization. RESULTS: Preoperative visualization in group A was 88% (mean 2.0 sentinel nodes per patient) versus 100% in group B (mean 2.6 sentinel nodes per patient). Visualization scores (p=0.008), total counts (p=0.001) and maximum counts per pixel (p=0.034) in the sentinel nodes were significantly better in group B. This also led to more efficient intraoperative detection of the sentinel nodes with the portable gamma camera (84% in group A versus 100% in group B). CONCLUSION: Enhancement of the particle concentration may lead to significant improvement in sentinel node visualization and intraoperative localization in patients with prostate cancer. Further research regarding optimization of radiotracer labelling by changing the particle concentration is warranted. PMID- 20306034 TI - SPECT imaging of GABA(A)/benzodiazepine receptors and cerebral perfusion in mild cognitive impairment. AB - PURPOSE: The involvement of neocortical and limbic GABA(A)/benzodiazepine (BZD) receptors in Alzheimer's disease (AD) is controversial and mainly reported in advanced stages. The status of these receptors in the very early stages of AD is unclear and has not been explored in vivo. Our aims were to investigate in vivo the integrity of cerebral cortical GABA(A)/BZD receptors in subjects with amnestic mild cognitive impairment (MCI) and to compare possible receptor changes to those in cerebral perfusion. METHODS: [(123)I]Iomazenil and [(99m)Tc]HMPAO SPECT images were acquired in 16 patients with amnestic MCI and in 14 normal elderly control subjects (only [(123)I]iomazenil imaging in 5, only [(99m)Tc]HMPAO imaging in 4, and both [(123)I]iomazenil and [(99m)Tc]HMPAO imaging in 5). Region of interest (ROI) analysis and voxel-based analysis were performed with cerebellar normalization. RESULTS: Neither ROI analysis nor voxel based analysis showed significant [(123)I]iomazenil binding changes in MCI patients compared to control subjects, either as a whole group or when considering only those patients with MCI that converted to AD within 2 years of clinical follow-up. In contrast, the ROI analysis revealed significant hypoperfusion of the precuneus and posterior cingulate cortex in the whole group of MCI patients and in MCI converters as compared to control subjects. Voxel based analysis showed similar results. CONCLUSION: These results indicate that in the very early stages of AD, neocortical and limbic neurons/synapses expressing GABA(A)/BZD receptors are essentially preserved. They suggest that in MCI patients functional changes precede neuronal/synaptic loss in neocortical posterior regions and that [(99m)Tc]HMPAO rCBF imaging is more sensitive than [(123)I]iomazenil GABA(A)/BZD receptor imaging in detecting prodromal AD. PMID- 20306035 TI - Guidance on current good radiopharmacy practice (cGRPP) for the small-scale preparation of radiopharmaceuticals. AB - This guidance is meant as a guidance to Part B of the EANM "Guidelines on Good Radiopharmacy Practice (GRPP)" issued by the Radiopharmacy Committee of the EANM (see www.eanm.org ), covering the small-scale "in house" preparation of radiopharmaceuticals which are not kit procedures. The aim is to provide more detailed and practice-oriented guidance to those who are involved in the small scale preparation of, for example, PET, therapeutic or other radiopharmaceuticals which are not intended for commercial purposes or distribution. PMID- 20306037 TI - Anatomy-based reconstruction of FDG-PET images with implicit partial volume correction improves detection of hypometabolic regions in patients with epilepsy due to focal cortical dysplasia diagnosed on MRI. AB - PURPOSE: Detection of hypometabolic areas on interictal FDG-PET images for assessing the epileptogenic zone is hampered by partial volume effects. We evaluated the performance of an anatomy-based maximum a-posteriori (A-MAP) reconstruction algorithm which combined noise suppression with correction for the partial volume effect in the detection of hypometabolic areas in patients with focal cortical dysplasia (FCD). METHODS: FDG-PET images from 14 patients with refractory partial epilepsy were reconstructed using A-MAP and maximum likelihood (ML) reconstruction. In all patients, presurgical evaluation showed that FCD represented the epileptic lesion. Correspondence between the FCD location and regional metabolism on a predefined atlas was evaluated. An asymmetry index of FCD to normal cortex was calculated. RESULTS: Hypometabolism at the FCD location was detected in 9/14 patients (64%) using ML and in 10/14 patients (71%) using A MAP reconstruction. Hypometabolic areas outside the FCD location were detected in 12/14 patients (86%) using ML and in 11/14 patients (79%) using A-MAP reconstruction. The asymmetry index was higher using A-MAP reconstruction (0.61, ML 0.49, p=0.03). CONCLUSION: The A-MAP reconstruction algorithm improved visual detection of epileptic FCD on brain FDG-PET images compared to ML reconstruction, due to higher contrast and better delineation of the lesion. This improvement failed to reach significance in our small sample. Hypometabolism outside the lesion is often present, consistent with the observation that the functional deficit zone tends to be larger than the epileptogenic zone. PMID- 20306036 TI - Molecular imaging in atherosclerosis. AB - Atherosclerosis is the major cause of cardiovascular disease, which still has the leading position in morbidity and mortality in the Western world. Many risk factors and pathobiological processes are acting together in the development of atherosclerosis. This leads to different remodelling stages (positive and negative) which are both associated with plaque physiology and clinical presentation. The different remodelling stages of atherosclerosis are explained with their clinical relevance. Recent advances in basic science have established that atherosclerosis is not only a lipid storage disease, but that also inflammation has a fundamental role in all stages of the disease. The molecular events leading to atherosclerosis will be extensively reviewed and described. Further on in this review different modalities and their role in the different stages of atherosclerosis will be discussed. Non-nuclear invasive imaging techniques (intravascular ultrasound, intravascular MRI, intracoronary angioscopy and intravascular optical coherence tomography) and non-nuclear non-invasive imaging techniques (ultrasound with Doppler flow, electron-bean computed tomography, coronary computed tomography angiography, MRI and coronary artery MR angiography) will be reviewed. After that we focus on nuclear imaging techniques for detecting atherosclerotic plaques, divided into three groups: atherosclerotic lesion components, inflammation and thrombosis. This emerging area of nuclear imaging techniques can provide measures of biological activity of atherosclerotic plaques, thereby improving the prediction of clinical events. As we will see in the future perspectives, at present, there is no special tracer that can be called the diagnostic tool to diagnose prospective stroke or infarction in patients. Nevertheless, we expect such a tracer to be developed in the next few years and maybe, theoretically, it could even be used for targeted therapy (in the form of a beta-emitter) to combat cardiovascular disease. PMID- 20306038 TI - PSA doubling time for prediction of [(11)C]choline PET/CT findings in prostate cancer patients with biochemical failure after radical prostatectomy. AB - PURPOSE: Previous studies have shown that the positive detection rate of [(11)C]choline positron emission tomography/computed tomography (PET/CT) depends on prostate-specific antigen (PSA) plasma levels. This study compared PSA levels and PSA doubling time (PSADT) to predict [(11)C]choline PET/CT findings. METHODS: PSADT was retrospectively calculated in 170 prostate cancer (PCa) patients with biochemical failure after radical prostatectomy who underwent [(11)C]choline PET/CT. PSADT was calculated as PSADT = ln2/m, where m is the slope of the linear regression line of the natural log of PSA values. At least three PSA measurements were used (median: 4; range: 3-16), separated by at least 3 months, each with a minimum increase of 0.20 ng/ml. PET/CT findings were validated using criteria based on histological analysis and clinical and imaging data. Statistical analysis was performed using the t test, chi-square test, analysis of variance and binary logistic regression. Regression-based coefficients were used to develop a nomogram predicting the probability of positive [(11)C]choline PET/CT and 200 bootstrap resamples were used for internal validation. RESULTS: The median PSA was 1.25 ng/ml (range: 0.23-48.6 ng/ml), and the median PSADT was 7.0 months (range: 0.97-45.3 months). [(11)C]choline PET/CT was positive in 75 of 170 patients (44%). PET/CT findings were validated using histological criteria (11%) and clinical and imaging criteria (89%). The overall accuracy of [(11)C]choline PET/CT was 88%. Multivariate logistic regression showed that high PSA and short PSADT were significant (p < 0.05) predictors of positive [(11)C]choline PET/CT [PSA: odds ratio (OR) = 1.43; 95% confidence interval (CI): 1.15-1.78; PSADT: OR = 1.12; 95% CI: 1.04-1.21]. The percentage of patients with positive [(11)C]choline PET/CT was 27% for PSADT >6 months, 61% for PSADT between 3 and 6 months and 81% for PSADT <3 months. The percentage of patients who displayed pathological [(11)C]choline uptake in the skeleton significantly increased (p < 0.05) from 3% for PSADT >6 months to 52% for PSADT <3 months. Conversely, patients who displayed pathological [(11)C]choline uptake in the prostatectomy bed were 0% for PSADT <3 months and 17% for PSADT >6 months (p < 0.05). A nomogram based on age, PSA, PSADT, time to trigger PSA, Gleason score, pathological stage and androgen deprivation therapy demonstrated bootstrap corrected predictive accuracy of 81%. CONCLUSION: Like PSA, PSADT is an independent predictor of [(11)C]choline PET/CT. [(11)C]choline PET/CT is very sensitive to PCa tumour growth, as reflected by PSA kinetics. PSADT should be taken into account by physicians when referring PCa patients for [(11)C]choline PET/CT. PMID- 20306039 TI - ALARA in rhTSH-stimulated post-surgical thyroid remnant ablation: what is the lowest reasonably achievable activity? PMID- 20306040 TI - 18F-FDG versus 11C-choline PET/CT for the imaging of advanced head and neck cancer after combined intra-arterial chemotherapy and radiotherapy: the time period during which PET/CT can reliably detect non-recurrence. AB - PURPOSE: The purpose of this prospective study was to evaluate the usefulness of (18)F-fluorodeoxyglucose (FDG) and (11)C-choline positron emission tomography (PET)/computed tomography (CT) for detecting recurrences of advanced head and neck cancer after combined intra-arterial chemotherapy and radiotherapy. Additionally, we surveyed the time period during which an effective negative predictive value could be maintained after the first follow-up PET/CT examination and estimated the optimal timing of a second PET/CT examination for detecting late recurrences. METHODS: Fifty-three subjects (36 men and 17 women; mean age: 59.4 +/- 11.5 years) with advanced head and neck squamous cell carcinoma were recruited. Post-treatment (18)F-FDG PET/CT and (11)C-choline examinations were performed in all patients between 8 and 12 weeks after combined intra-arterial chemotherapy and radiotherapy. The PET/CT images were evaluated using a patient based analysis and a lesion-based analysis. All of the patients were prospectively followed for at least 9 months after the post-treatment PET/CT examination, with surveillance using conventional images (including CT and/or MRI) and a physical examination performed every 3 months. RESULTS: Recurrences, as determined using the patient-based analysis, were eventually confirmed in 18, 6 and 5 patients at 3, 4-6 and 7-9 months after the post-treatment PET/CT examination, respectively. The sensitivity and specificity of the 18F-FDG PET/CT and the 11C-choline PET/CT examinations to predict recurrence within 3 months were higher (FDG: 89 and 91%; choline: 83 and 80%, respectively) than for recurrence detection 6 months (FDG: 67 and 90%; choline: 62 and 76%, respectively) and 9 months later (FDG: 59 and 92%; choline: 55 and 75%, respectively). The lesion-based analysis showed that the maximum standardized uptake value of (18)F-FDG and (11)C-choline in the recurrent lesions were correlated with each other, compared with their relation in scar tissues (R (2) = 0.492 and 0.197, respectively). CONCLUSION: (11)C-choline was not superior to (18)F-FDG for the detection of recurrent head and neck cancer. Both modalities had difficulty identifying recurrences at 4-9 months after the post-treatment PET/CT examination. In patients with advanced head and neck cancer who have received combined therapy, a second post-treatment PET/CT examination to check for late recurrences should be performed within 4-6 months after the first post treatment PET/CT examination. PMID- 20306041 TI - (E)-4-hydroxy-3-methyl-but-2 enyl pyrophosphate-stimulated Vgamma9Vdelta2 T cells possess T helper type 1-promoting adjuvant activity for human monocyte-derived dendritic cells. AB - Vgamma9Vdelta2 T cells respond to pyrophosphate antigens and display potent antitumour activity in vitro. We have investigated the potential of the most potent phosphoantigen known to activate Vgamma9Vdelta2 T cells, (E)-4-hydroxy-3 methyl-but-2 enyl pyrophosphate (HMB-PP), as an adjuvant for dendritic cell (DC) based vaccines. A single stimulation of peripheral blood mononuclear cells with HMB-PP and IL-2 was sufficient to generate lines of effector memory Vgamma9Vdelta2 T cells that retained their cytolytic and cytokine secretion activities. These cells induced differentiation of DC into semi-mature antigen presenting cells expressing CD86, CD11c, CD54, HLA-DR, CD83 and CD40, which secreted low levels of bioactive IL-12 but no IL-10. Vgamma9Vdelta2 T cells also strongly costimulated IL-12 release but inhibited IL-10 production by lipopolysaccharide (LPS)-stimulated DC. When substituted for Vgamma9Vdelta2 T cells, IFN-gamma did not induce full DC maturation but it augmented IL-12 and inhibited IL-10 release by LPS-stimulated DC, in a manner similar to HMB-PP activated Vgamma9Vdelta2 T cells. Our findings indicate that Vgamma9Vdelta2 T cells, stimulated with nanomolar concentrations of HMB-PP, strongly promote T helper type 1 (Th1) responses through their ability to induce DC maturation and IL-12 secretion. This adjuvant activity may prove useful in DC-based cancer therapies. PMID- 20306042 TI - Environmental indicators to assess the risk of diffuse Nitrogen losses from agriculture. AB - Diffuse Nitrogen (N) loss from agriculture is a major factor contributing to increased concentrations of nitrate in surface and groundwater, and of N(2)O and NH(3) in the atmosphere. Different approaches to assess diffuse N losses from agriculture have been proposed, among other direct measurements of N loads in leachate and groundwater, and physically-based modelling. However, both these approaches have serious drawbacks and are awkward to use at a routine base. N loss indicators (NLIs) are environmental management tools for assessing the risk of diffuse N losses from agricultural fields. They range in complexity from simple proxy variables to elaborate systems of algebraic equations. Here we present an overview of NLIs developed in different parts of the world. NLIs can be categorized into source-based, transport-based, and composite approaches. Several issues demand more attention in future studies. (1) Is incorporation of leaching losses and gaseous losses into one single NLI warranted? (2) Is it sufficient to restrict the focus on the rooted soil zone without considering the vadose zone and aquifer? (3) Calibration and validation of NLIs using field data of N loss seems not sufficient. Comparisons of several different NLIs with each other needs more attention; however, the different scaling of NLIs impedes comparability. (4) Sensitivity of input parameters with regard to the final NLI output needs more attention in future studies. (5) For environmental management purposes, factors addressing management decision by farmers deserve more attention. PMID- 20306043 TI - Anxious personality and breast cancer: possible negative impact on quality of life after breast-conserving therapy. AB - BACKGROUND: Quality of Life (QoL) is an important outcome measure in oncology. To assess the influence of surgical treatment and personality on QoL in women with breast cancer, a longitudinal prospective cohort study was done. METHODS: Women (n = 222) completed questionnaires concerning QoL (WHOQOL 100) and personality (NEO-FFI and STAI) prior to the diagnosis of breast cancer and 1, 3, 6, and 12 months after diagnosis and treatment. One hundred five women were treated with breast-conserving therapy (BCT) and 117 women underwent mastectomy (MTC). RESULTS: The two treatment groups did not differ on overall QoL. At all measurement times the influence of trait anxiety on overall QoL was substantial in the BCT group. Women with a high score on trait anxiety were seven times more likely to have a low overall QoL 1 year after BCT. In the MTC group overall QoL was influenced mainly by neuroticism. CONCLUSIONS: Personality, especially trait anxiety and neuroticism, determined patients' overall QoL scores. Women with an anxious personality fared worse concerning QoL after breast conserving therapy. PMID- 20306044 TI - [Neuroendocrine tumors of the stomach. Risk stratification and therapy]. AB - The diagnosis and therapy of neuroendocrine tumors (NETs) of the stomach are based on their exact classification and risk stratification. Since the incidence of gastric NETs has risen sharply over the last 35 years and most tumors are detected endoscopically at an early stage, they have come to represent a challenge for the pathologist. Gastric NETs are classified according to the WHO and TNM classifications and additionally separated into four biologically distinct types: Well differentiated type 1 and 2 gastric NETs (G1) smaller than 2 cm, and type 3 smaller than 1 cm that do not infiltrate the muscularis propria or show angioinvasion have a good prognosis and can be removed endoscopically. Well differentiated type 1 and 2 gastric NETs (G1-G2) larger than 2 cm or type 3 with a diameter above 1 cm or with infiltration of the muscular wall and/or angioinvasion and poorly differentiated (type 4) neuroendocrine carcinomas carry a poor prognosis and need to be treated aggressively. Endosonography is the method of choice for determining the size, depth of infiltration and presence of lymph node metastases. With exact diagnosis and adequate treatment, the majority of patients with gastric NETs have a favorable prognosis. PMID- 20306045 TI - Determination of the position on which the median nerve compression is at the lowest in carpal tunnel syndrome and clinical effectiveness of custom splint application. AB - To evaluate the clinical effectiveness of wrist splint usage arranged by determining the optimal position on which the median nerve is compressed the least through sonographic examination for patients with carpal tunnel syndrome (CTS). This study was a prospective, clinical trial with a 6-week follow-up. Twenty-four patients diagnosed clinically and electromyographically with CTS were included in the study. A total of 37 wrists were studied on. When the patients were grouped according to the optimal position, Group I comprising 16 (43.24%) wrists was at 15 degree flexion, Group II comprising 12 (32.43%) wrists was neutral, Group III comprising 6 (16.22%) wrists was at 15 degrees extension and Group IV comprising 3 (8.11%) wrists was at 30 degrees extension configurations. Groups I, II and III were included in clinical follow-up. Symptom severity score (SSS), functional status score (FSS), Grip strength and Pinch strength were used for the clinical follow-up and evaluation of the patients. When pre- and post treatment were compared, a statistically significant recovery was detected in all three groups in respect to SSS (Group I P < 0.01, Group II P < 0.05, Group III P < 0.05). A statistically significant recovery was detected for FSS only in Group I (P < 0.05) and for Grip strength in Group II (P < 0.05). When the groups were compared among themselves, no statistically significant difference was detected for any of the parameters (P > 0.05). In this study, by sonographic examination of the patients included in the study with CTS, we saw that the optimal position on which the median nerve is compressed the least varies depending on the individual and we determined that this position was 15 degrees flexion most frequently for our patients. We also observed that in clinical follow-up of wrist splint usage arranged on custom optimal position results in significant recovery. PMID- 20306046 TI - Massage therapy for fibromyalgia symptoms. AB - Massage therapy is widely used by patients with fibromyalgia seeking symptom relief. We performed a review of all available studies with an emphasis on randomized controlled trials to determine whether massage therapy can be a viable treatment of fibromyalgia symptoms. Extensive narrative review. PubMed, PsychInfo, CINAHL, PEDro, ISI Web of Science, and Google Scholar databases (inception-December 2009) were searched for the key words "massage", "massotherapy", "self-massage", "soft tissue manipulation", "soft tissue mobilization", "complementary medicine", "fibromyalgia" "fibrositis", and "myofascial pain". No language restrictions were imposed. The reference lists of all articles retrieved in full were also searched. The effects of massage on fibromyalgia symptoms have been examined in two single-arm studies and six randomized controlled trials. All reviewed studies showed short-term benefits of massage, and only one single-arm study demonstrated long-term benefits. All reviewed studies had methodological problems. The existing literature provides modest support for use of massage therapy in treating fibromyalgia. Additional rigorous research is needed in order to establish massage therapy as a safe and effective intervention for fibromyalgia. In massage therapy of fibromyalgia, we suggest that massage will be painless, its intensity should be increased gradually from session to session, in accordance with patient's symptoms; and the sessions should be performed at least 1-2 times a week. PMID- 20306047 TI - Osteoanabolic therapy: a non-surgical option of treatment for Kummell's disease? AB - Kummell's disease is the current eponym of avascular osteonecrosis (AVN) of a vertebral body leading to a delayed non-healing vertebral compression fracture (VCF) and thus pseudo-arthrosis. AVN is characterized by production of gas that outlines a radiolucent zone in the vertebral body, called vacuum cleft sign (VCS) or "Kummell's sign". This sign has been observed in up to one-third of VCFs and is often associated with osteoporosis and never with malignant or inflammatory diseases. Generally, treatment strategies are conservative management and percutaneous vertebroplasty. Teriparatide (rhPTH [1-34]) is an osteoanabolic agent approved for treatment of osteoporosis and helpful in fracture's healing too. Here, we describe the case of an 81-year-old osteoporotic woman presented with a 1-year history of persistent low back pain onset after a trauma. A lumbar spine Computer Tomography (CT) scan performed 2 months after the injury (November 2006) showed the VCS within a VCF of the first lumbar vertebra; a control CT scan 1 year later showed persistence of the finding. After 12 months of treatment with teriparatide 20 mcg/day, symptoms disappeared and vacuum was significantly reduced. In conclusion, Kummell's disease may be hypothesized in patients with chronic spinal symptoms, especially in the presence of osteoporosis. Moreover in this condition, osteoanabolic treatment may be used in patients with Kummell's disease to enhance vertebral fracture's healing and contribute to back pain relief. PMID- 20306048 TI - Clonal expansions in selected TCR BV families of rheumatoid arthritis patients are reduced by treatment with the TNFalpha inhibitors etanercept and infliximab. AB - Clonal expansions of autoreactive CD4+ T cells are frequently present in patients with rheumatoid arthritis (RA) and are stable over long periods of time. This study was undertaken to investigate the influence of anti-TNFalpha treatment on such clonal expansions in the peripheral CD4+ T-cell compartment. TNFalpha inhibiting therapies significantly reduced the total number of expanded clonotypes. This effect was mainly observed in clonal expansions in the BV6 family, while in clonal expansions of the BV14 family no such effect was seen. No change in the percentage of CD4+ CD28 null T cells was observed. Serum concentrations of the pro-homeostatic cytokine IL-7 were found to increase in patients responding TNFalpha-inhibiting therapy. These data argue for a normalization of adaptive immune mechanisms under TNFalpha inhibiting therapies, which may be secondary to the control of inflammation but contribute to the efficacy of cytokine blockade therapy. PMID- 20306049 TI - Lack of association of TLR4 gene Asp299Gly and Thr399Ile polymorphisms with rheumatoid arthritis in Chinese Han population of Yunnan Province. AB - Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by chronic inflammation of synovium and subsequent joint destruction. Recently, genetic polymorphisms within the toll-like receptor 4 (TLR4) genes have been reported to be associated with RA. To analyze the association between the genetic polymorphisms within TLR4 gene and the susceptibility to RA in Chinese people, two functional variants, Asp299Gly and Thr399Ile, in the TLR4 gene were genotyped using polymerase chain reaction-restriction fragment length polymorphism (PCR RFLP) and direct sequencing techniques from 213 RA patients and 247 ethnically matched controls. None polymorphisms of Asp299Gly and Thr399Ile were detected in all RA cases and controls, which indicates that there is no relevance between these two SNPs and RA in the Chinese Han population. Further studies with extended single nucleotide polymorphisms (SNP) should be performed. PMID- 20306050 TI - Posterior reversible encephalopathy during an attack of familial Mediterranean fever. AB - Reported here is a 19-year-old female patient with familial Mediterranean fever who was seen for altered mental status and seizures. She was eventually diagnosed to have posterior reversible leukoencephalopathy syndrome. Although a variety of conditions have been reported in association with this syndrome, to our best notice, this is the second case in whom familial Mediterranean fever and posterior reversible leukoencephalopathy coexists. PMID- 20306051 TI - Inhibition of the expression of the starch synthase II gene leads to lower pasting temperature in sweetpotato starch. AB - The sweetpotato cultivar Quick Sweet (QS) with a lower pasting temperature of starch is a unique breeding material, but the biochemical background of this property has been unknown. To assess the physiological impact of the reduced isoform II activity of starch synthase (SSII) on the starch properties in sweetpotato storage root, transgenic sweetpotato plants with reduced expressions of the SSII gene were generated and evaluated. All of the starches from transgenic plants showed lower pasting temperatures and breakdown measured by a Rapid Visco Analyzer. The pasting temperatures in transgenic plants were approximately 10-15 degrees C lower than in wild-type plants. Distribution of the amylopectin chain length of the transgenic lines showed marked differences compared to that in wild-type plants: more chains with degree of polymerization (DP) 6-11 and fewer chains with DP 13-25. The starch granules from the storage root of transgenic plants showed cracking on the hilum, while those from wild type plants appeared to be typical sweetpotato starch. In accordance with these observations, the expression of SSII in the storage roots of the sweetpotato cultivar with low pasting temperature starch (QS) was notably lower than in cultivars with normal starch. Moreover, nucleotide sequence analysis suggested that most of the SSII transcripts in the cultivar with low pasting temperature starch were inactive alleles. These results clearly indicate that the activity of SSII in sweetpotato storage roots, like those in other plants, affects the pasting properties of starch through alteration of the amylopectin structure. PMID- 20306052 TI - The green fluorescent protein as an efficient selection marker for Agrobacterium tumefaciens-mediated transformation in Hevea brasiliensis (Mull. Arg). AB - An efficient genetic transformation procedure using a recombinant green fluorescent protein (GFP) has been developed in Hevea brasiliensis clone PB260. Transformation experiments have been performed using an Agrobacterium tumefaciens binary vector harbouring both uidA and S65T-GFP reporter genes in order to compare selection methods using glucuronidase assay (GUS activity) and paromomycin resistance, GFP activity and paromomycin resistance, or GFP activity only. At transient level, the number of spots showing GUS or GFP activities was similar for 4 and 5 days after coculture. After selection, stable transformation events were observed and led to the establishment of transgenic callus lines. A higher number of lines were generated with GFP selection compared to the GUS one. GFP selection is less time-consuming in terms of callus subculturing, and offers the possibility of producing antibiotic resistance marker-free transgenic plants. PMID- 20306053 TI - Clinical observation on 2 micron laser for non-muscle-invasive bladder tumor treatment: single-center experience. AB - OBJECTIVES: To evaluate the efficacy and safety of 2 micron continuous wave laser resection of non-muscle-invasive bladder tumor (NMIBT) compared with holmium laser resection of bladder tumor (HoLRBT) and standard transurethral resection of bladder tumor (TURBT). METHODS: Since April 2006 to August 2007, 97 patients with NMIBT were retrospectively collected in this study. All of them were classified into 3 groups, which were treated with 2 micron continuous wave laser resection, holmium laser resection and TURBT, respectively. The preoperative, intraoperative and postoperative clinical data were recorded and compared using SAS 6.12 statistical software. RESULTS: There were no differences with the preoperative characteristics among the three groups, except the diameter of the tumors. The maximum diameter of the tumors in 2 micron laser group was larger than the other two groups (P < 0.05). Two micron laser group was associated with less hemoglobin decrease compared with TURBT group (P < 0.05). All of the patients were followed and the recurrence rate of the three groups indicated no statistical significance (P > 0.05). CONCLUSIONS: In conclusion, 2 micron continuous wave laser resection of non-muscle-invasive bladder tumor is a safe and reliable treatment. With the distinguished hemostasis, it is an available optional treatment. PMID- 20306055 TI - First coinjointed meeting of the Spanish and French Pediatric Neurosurgical Societies. PMID- 20306054 TI - [Epidemiology of and preventive measures for multiresistant pathogens]. AB - Multidrug-resistant organisms (MROs) are increasing all over the world. The most important MROs are methicillin-resistant S. aureus, followed by vancomycin resistant enterococci and extended-spectrum beta-lactamase (ESBL)-producing bacteria. The latter are not yet of much importance in ophthalmology. MROs can cause serious infections and must be considered in empiric therapy of nosocomial infections. To prevent further spread, standard and contact precautions have to be followed, and antibiotic stewardship needs to be introduced. PMID- 20306056 TI - Intrathecal baclofen therapy for spasticity of cerebral origin--does the position of the intrathecal catheter matter? AB - OBJECTIVE: To assess the correlation between the position of the intrathecal baclofen therapy catheter with the clinical outcome and response to the spasticity. METHODS AND RESULTS: A prospective cohort study was done by reviewing the paediatric group of patients with spasticity of cerebral origin who had insertion of a programmable baclofen pump for intrathecal administration in the last 10 years (August 1998 to September 2007). A total of 190 procedures were carried out in 166 patients, under a single paediatric neurosurgeon, with an age range of 18 months-16 years (mean 8.75 years) with follow up of 1-10 years (mean 5 years). The routine post-operative X-rays, which were done as per protocol, were reviewed, and the position of the intrathecal catheter tip was documented in relation to the vertebral bodies. The maintenance intrathecal baclofen dose was 25 microgms to 1,000 microgms (mean 255.8 microgms) based on the clinical response to spasticity. Statistical analysis was carried out to assess the correlation of the position of the tip of the intrathecal catheter with the outcome in spasticity based on GMFCS (Gross Motor Function Classification System) and Ashworth score. CONCLUSION: In our series, there was no statistically significant correlation between the position of the intrathecal catheter and the clinical response to the spasticity. PMID- 20306057 TI - Safety and efficacy of continuous morphine infusions following pediatric cranial surgery in a surgical ward setting. AB - PURPOSE: Morphine is avoided by many neurosurgeons following cranial surgery. There exists a concern regarding the potential complications and a perception that cranial surgery is less painful than other surgical procedures. At British Columbia Children's Hospital continuous morphine infusions (CMI) have been used to control pain in pediatric neurosurgical patients. The purpose of this study was to compare the safety and efficacy of continuous intravenous morphine infusion to standard oral analgesics in a neurosurgical ward setting. METHODS: A retrospective review of medical records for 71 children was completed. The patients underwent either cranial reconstruction (2002-2007) or craniotomies for intradural pathology (2005-2007) at British Columbia Children's Hospital. Outcome measures included pain control and adverse events. Comparison was made between patients receiving a CMI and patients receiving acetaminophen and codeine. RESULTS: Thirty-seven children received CMI on the ward (30 cranial reconstruction and 7 craniotomy), while 34 (10 cranial reconstruction and 24 craniotomy) received acetaminophen and codeine. There was no statistical difference in pain control. There was significantly more nausea on post-operative day one in the CMI group (p = 0.002). There were no other significant adverse events. CONCLUSIONS: These findings suggest that CMI is comparable to acetaminophen and codeine with respect to analgesia and serious side effects. We recommend the use of CMIs as an alternative when pain is poorly controlled in post-operative pediatric neurosurgical patients to prevent the potential adverse consequences of inadequate analgesia. PMID- 20306058 TI - Expression and prognostic value of the Ki-67 in Wilms' tumor: experience with 48 cases. AB - PURPOSE: Ki-67, tumor proliferation marker, is an important prognostic factor in a variety of cancers. In the present study, we investigated the expression and the prognostic value of Ki-67 in nephroblastoma. METHODS: Ki-67 expressions were investigated by immunohistochemistry on paraffin-embedded material in 48 children operated on because of nephroblastoma. Patients were treated according to SIOP protocol. The mean follow-up period was 5.4 years. A proliferation index was obtained by immunohistochemistry using anti-Ki-67 anti-body. RESULTS: The mean Ki 67 proliferation index in the blastemal type was 12.3%, and in the epithelial type, 21.4%. In the anaplastic type, Ki-67 proliferation index was: in the blastemal component 20%, in the stromal 21%, and in the epithelial 31%. In the mixed tumor type, Ki-67 proliferation index was assessed as: in the blastemal component 10%, in the epithelial 33% and in the stromal 31.5%. Proliferation index for the epithelium was significantly higher than those found for the blastema (P = 0.001). A correlation between Ki-67 and tumor stage found proliferation index significantly higher in stages I and II (P = 0.002). CONCLUSION: The results support the conclusion that Ki-67 is a relevant marker for assessing the proliferative activity and tumor cell dynamics of nephroblastoma, but it may not be a good clinical prognostic marker. PMID- 20306059 TI - Genomics approach to the analysis of bacterial communities dynamics in Hirschsprung's disease-associated enterocolitis: a pilot study. AB - INTRODUCTION: The most invalidating and life-threatening complication in Hirschsprung's disease patients (HSCR) is Hirschsprung's disease-associated enterocolitis (HAEC). The mechanisms underlying enterocolitis have not been identified. The limited knowledge of the role of intestinal microflora is in part due to the complexity of the intestinal microbiome and to the limitation of cultivation-based technologies, given that less than 25% of the intestinal bacterial species can be cultured. MATERIALS AND METHODS: We used amplified ribosomal DNA restriction analysis (ARDRA) with four different restriction enzymes to study variations of microflora composition of the stools of a selected HSCR patient in different clinical conditions (acute phase vs. remission). RESULTS: We assessed a total of 15 stool specimens belonging to the same 3-year old male patient suffering from HSCR, which were harvested during 4 HAEC episodes and remission phases. Restriction analysis showed that HAEC episodes seem to cluster together at ARDRA analysis, thus suggesting a sort of predisposing bacterial community for HAEC development and the need for a microflora equilibrium to maintain wellness. CONCLUSIONS: This approach proved to be effective, useful and powerful in assessing microflora dynamics and indicated that the differences in microflora associated with acute HAEC or remission are likely to result from a combination of disease activity and different antibiotic therapies. ARDRA proved to be useful in discriminating disease versus remission. Our findings indicated that HAEC results from a change in the equilibrium between bacterial species or from altered discrimination of harmless from harmful microorganisms, challenging the definition of pathogenic and non-pathogenic species. Based on these results, we propose ARDRA as a rapid inexpensive tool to assess microflora dynamics during HAEC episodes. PMID- 20306061 TI - Boerhaave's syndrome secondary to colonic interposition graft perforation. PMID- 20306060 TI - Colonic transit time in mentally retarded persons. AB - INTRODUCTION: Constipation is frequently seen in patients with mental retardation (MR). Its pathophysiology is poorly understood. Measurement of colon transit time (CTT) differentiates between retentive and non-retentive constipation. AIM: To determine total and segmental CTT in MR patients compared to healthy controls. METHOD: Of 250 residents, 60 patients older then 16, without swallowing disorder or scoliosis, are randomly chosen, 58 participated (intelligence quotient < 50, median age 35.5 year, 29 male). Constipation was defined as less than three defecations a week. Controls are 32 non-constipated age-matched healthy volunteers (median age 29 year, 19 male). CTT is measured by daily administration of ten radio-opaque markers during 6 days and abdominal X-ray on day 7. CTT is calculated using Bouchoucha's [7] method. RESULTS: Compared to controls, total CTT is significantly (P < 0.001) longer in MR (median 22.8 h vs. 57.6 h, respectively). Of the MR patients, 21/58 (36%) are constipated. The mental retardated and constipated (MRC) have a significant prolonged CTT in all segments (P < 0.01; median right CTT 19.2 h vs. 4.8 h; left CTT 14.4 h vs. 4.8 h; rectosigmoidal CTT 42 h vs. 9.6 h), whereas in mental retarded non-constipated (MRNC) persons, the rectosigmoidal CTT is prolonged (median 21.6 h vs. 9.6 h). CONCLUSION: Patients with moderate to deep MR have a significantly prolonged total CTT. In MRNC persons, rectosigmoidal CTT prolongation suggests a defecation problem. In MRC, CTT is prolonged in all segments, suggesting diffuse colonic inertia problem. PMID- 20306062 TI - Necrotising fasciitis of the lower limb due to diverticular disease of the sigmoid colon. PMID- 20306063 TI - Factors affecting the latency period in patients with preterm premature rupture of membranes. AB - OBJECTIVE: The objective of the study was to assess the factors affecting the latency period in woman with preterm premature rupture of membranes (PPROM) and evaluate morbidity associated with prolonged latency. STUDY DESIGN: A population based retrospective study including all women with PPROM (prior to 37 weeks' gestation) during the years 1998-2008 was conducted. Comparison of the latency period was conducted by the Mann-Whitney U test since the latency period was not normally distributed (most delivered in 24 h). Multivariable logistic regression model was constructed to find independent factors associated with prolonged latency period (>72 h). RESULTS: During the study period, there were 1,399 singleton deliveries of patients with PPROM; 24.6% (345) occurred prior to 34 weeks' gestation. The duration of the latency period was significantly longer among woman with PPROM before 34 weeks as compared to PPROM after 34 weeks' gestation (5.78 vs. 2.02 days; p < 0.001). Other factors associated with longer latency period were multiparity (more than one previous delivery) and maternal age >35. Using a multivariable analysis, the following factors were significantly associated with latency period >72 h: lower gestational age (weeks, OR = 0.8, 95% CI 0.77-0.84; p < 0.001) and multiparity (OR = 1.7, 95% CI 1.3-2.2; p < 0.001). Prolonged latency period (>72 h) was significantly associated with chorioamnionitis (OR = 2.095, 95% CI 1.44-3.04; p < 0.001) and oligohydramnios (OR = 3.041, 95% CI 1.43-6.45; p = 0.004) but not with placental abruption (OR = 0.854, 95% CI 0.41-1.78; p = 0.674) or perinatal mortality (OR = 1.2, 95% CI 0.6 2.2; p = 0.556). CONCLUSION: The duration of the latency period is inversely associated with gestational age. Nulliparity is associated with lower latency period. Prolonged latency is a significant risk factor for chorioamnionitis. PMID- 20306064 TI - Intrapartum obturator neuropathy diagnosed after cesarean delivery. AB - Several postpartum neurologic injuries have been described in detail, while obturator nerve injuries are rarely reported. We report a woman who had weakness of the right leg and groin pain after cesarean delivery under general anesthesia. Obturator neuropathy was confirmed by electromyography and no compressive lesion of the nerve was seen on magnetic resonance imaging. The patient was treated conservatively and followed until she recovered fully. PMID- 20306065 TI - Plasma levels of C-reactive protein, leptin and glycosaminoglycans during spontaneous menstrual cycle: differences between ovulatory and anovulatory cycles. AB - PURPOSE: To assess the plasma levels of the inflammatory markers such as C reactive protein (CRP), leptin, and glycosaminoglycans (GAGs) during the menstrual cycle. METHODS: Eighteen healthy volunteers were divided into two groups according to the presence of ovulatory or anovulatory menstrual cycles. Blood samples were collected at different time points: at the menstrual phase (days 2-3), periovulatory phase (days 12-13), and luteal phase (days 23-24). CRP and leptin concentrations were measured by enzyme immunoassay. GAGs were isolated using ion-exchange chromatography on DEAE-Sephacel and quantified as hexuronate. The structural characterization of chondroitin sulfate (CS) isomers was performed by fluorophore-assisted carbohydrate electrophoresis (FACE). RESULTS: In the women with ovulatory cycles, plasma GAG levels differed significantly during menstrual cycle, with increased values at the periovulatory with respect to the menstrual phase. No significant differences in CRP and leptin concentrations were observed through the menstrual cycle in both the examined cycles, but inter-group analysis revealed significant differences of CRP and leptin levels between the ovulatory and anovulatory cycles with higher values at periovulatory phase in the ovulatory cycles. CONCLUSIONS: There are no fluctuations of both total GAG concentration and CS isomer content during menstrual cycle in the anovulatory cycles. A significant correlation between CRP and gonadotrophins was found. There is no significant difference in CRP across the menstrual cycle among ovulatory cycles, but there is a trend toward higher CRP at the periovulatory than the other phases, consistent with the significant difference in CRP between ovulatory and anovulatory cycles at the periovulatory phase. Both the trend and the significant result suggest an elevation in CRP with ovulation. These observations provide additional evidences to the hypothesis that the ovulation is an inflammatory-like phenomenon. PMID- 20306066 TI - Treatment of vocal fold scar by carbon dioxide laser and collagen injection: retrospective study on 12 patients. AB - Vocal fold scars are the result of injury to the vocal fold lamina propria. This condition leads to an impaired vibration and usually to poor voice quality. The purpose of our study was to compare the pre- and posttreatment voice assessment scores in patients treated by CO(2) laser-assisted freeing of the scar followed by collagen injection. A group of 12 patients (10 women and 2 men) with vocal fold scars was studied retrospectively. Voice assessment was based on stroboscopy and on perceptual scores using the Grade (G) of the GRABS scale, subjective evaluation by the use of the Voice Handicap Index (VHI), aerodynamic measurements [maximum phonation time (MPT) and phonation quotient (PQ)], and acoustical measurements (frequency range and low intensity). Stroboscopy showed an improvement on the mucosal vocal fold wave and on the glottic competence. The mean VHI was improved from 63.16 to 45.5; G from 2 to 1.41; MPT from 7.05 to 8.62 s; and PQ from 463.02 to 358.54 ml/s. CO(2) laser freeing of vocal fold scars followed by collagen injection, combined with speech therapy, improved significantly the aerodynamic parameters (efficiency of voice), but not the acoustical scores. PMID- 20306067 TI - Concha bullosa and septal deviation. AB - The aim of this study was to investigate the incidence of concha bullosa (CB) in cases with septal deviation (SD), correlation between the angle of deviation and degree of pneumatization and compare these correlations with qualitative and quantitative methods. We retrospectively searched our radiology database for all paranasal sinus computed tomography (CT) findings for 672 patients. All scans were grouped according to the presence and side of SD and/or CB. SD angles and pneumatization degree of the CB were measured with appropriate method. These findings were also classified according to the initial defined qualitative method. Generally, CB and SD incidences were 31.52 and 47.77%, respectively. CB ratio in SD patients was 45.34% whereas ratio in non-SD patients was 18.95%. Mean deviation angle of the isolated SD group (15.24 +/- 5.03) was found higher than both deviation angle of the unilateral CB + SD group (13.16 +/- 4.19) and bilateral CB + SD group (11.15 +/- 3.73) (P = 0.002, P = 0.0001 respectively). In conclusion, CB may tend to develop bilaterally in normal, non-deviated nose. However, the increasing incidence of unilateral CB, especially contralateral ones, in septal deviated patients suggested that SD may prevent the development of ipsilateral CB. PMID- 20306068 TI - William Macewen [1848-1924]. PMID- 20306069 TI - Bupivacaine-induced chemical meningitis. AB - We report a 34-year-old woman who, soon after a caesarian delivery with anesthesia by intrathecal bupivacaine hydrochloride injection, developed severe headache and high fever. Whereas C-reactive protein in the serum was normal, the cerebrospinal fluid (CSF) examination showed an increase in cell count (3,040/mm(3); mostly polymorphonuclear cells) and total protein (401 mg/dl), but only mildly decreased glucose content. No organisms were found by CSF staining and culture. Brain MRI scans were normal. Within 10 days after onset, her clinical conditions and CSF returned to normal. Considering previous reports, intrathecal bupivacaine hydrochloride seemed to be the most likely culprit for the development of chemical meningitis in our case. PMID- 20306070 TI - Long-term outcomes of Oxane Hd as intraocular tamponade in the treatment of complicated retinal detachment. AB - BACKGROUND: To evaluate the efficacy and safety of heavy silicone oil Oxane Hd as intraocular tamponade in the treatment of complicated retinal detachment (RD). METHODS: Forty eyes of 40 patients with complicated RD were recruited for this prospective study. Inclusion criteria were proliferative vitreoretinopathy grade > or = CP2, mainly inferior and posterior retinal breaks, or superior retinal breaks with patient's inability to posture. Oxane Hd was used as intraocular tamponade. The retinal status, the best-corrected visual acuity (BCVA) results, and any complications were observed. RESULTS: The mean duration of Oxane Hd endotamponade was 87.9 +/- 10.4 days, and the mean follow-up time after Oxane Hd removal was 438.1 +/- 153.7 days. The primary anatomical success rate after Oxane Hd removal was 87.5%, and with further intervention 97.5%. The BCVA significantly improved, from mean logMAR 2.12 +/- 0.60 to 1.38 +/- 0.59 (P < 0.001). The postoperative complications included temporary inflammatory reaction, moderately high intraocular pressure, heavy silicone oil emulsification, lens opacity and retinal proliferative membranes. CONCLUSIONS: Without a requirement for postoperative prone position, heavy silicone oil Oxane Hd is effective and safe for the treatment of complicated RD with inferior and posterior breaks. Larger groups and a longer follow-up period will be included to further evaluate the efficacy with Oxane Hd in superior retinal breaks. PMID- 20306072 TI - Novel KRIT1/CCM1 mutation in a patient with retinal cavernous hemangioma and cerebral cavernous malformation. AB - BACKGROUND: Retinal cavernous hemangiomas are rare vascular anomalies, and can be associated with cerebral cavernous malformations (CCM). Distinct mutations have been reported in patients who have both CCMs and retinal cavernous hemangiomas. METHODS: Fluorescein angiography, spectral domain optical coherence tomography, and genetic testing were performed on a patient with a retinal cavernous hemangioma and a CCM. RESULTS: Our patient was heterozygous in the KRIT1/CCM1 gene for a frameshift mutation, c.1088delC. This would be predicted to result in premature protein termination. DISCUSSION: We have identified a novel mutation in the KRIT1/CCM1 gene in a patient with both CCM and retinal cavernous hemangioma. We hypothesize that the occurrence of retinal cavernous hemangiomas and CCMs is underlaid by a common mechanism present in the KRIT1/CCM1 gene. PMID- 20306071 TI - Effects of luminance combinations on the characteristics of the global flash multifocal electroretinogram (mfERG). AB - PURPOSE: This study aims to ascertain the characteristics of the response triggered by the global flash multifocal electroretinogram (MOFO mfERG) under various combinations of global and focal flash luminance, and to determine the optimal conditions for this measurement. METHODS: Ten normal subjects with mean age 23.2 yrs (+/- 1.14 yrs) were recruited for the MOFO mfERG measurement. The visual stimulation consisted of four video frames (stimulus frame with 103 scaled hexagonal focal flashes, followed by a dark frame, a global flash and then another dark frame). The focal and global flash intensities were varied independently for four levels (50, 100, 200 and 400 cd/m(2)). The subjects then underwent measurements with sixteen combinations of focal and global flash luminance. The direct component (DC) and induced component (IC) of the MOFO mfERG were grouped into central and peripheral regions for analysis. RESULTS: The central and peripheral DC amplitude increased with the focal flash luminance under constant global flash luminance. Moreover, the proportion of the global flash and focal flash intensity was shown to be important to achieve an optimal IC response. When the ratio of global flash luminance to focal flash luminance (g/f ratio) was kept at about 2:1, the central and peripheral IC amplitude reached the peak value, and further increasing the global flash luminance would not enhance the IC response magnitude. The implicit time of both central and peripheral DC generally decreased with the increase of g/f ratio. However, the implicit time of central and peripheral IC increased with the g/f ratio. CONCLUSION: The g/f ratio is important in the MOFO mfERG paradigm, since the DC and IC responses change with this ratio. In order to obtain both optimal DC and IC responses, a g/f ratio of 1:1 with focal flash luminance between 100 cd/m(2) and 200 cd/m(2) would be recommended. As the global flash mfERG paradigm is studying the interaction triggered by both flashes, the g/f ratio is a vital parameter for measurement in future studies. PMID- 20306073 TI - Genotoxicity surveillance programme in workers dismantling World War I chemical ammunition. AB - PURPOSE: To evaluate the effectiveness of personal protective measures in a dismantling plant for chemical weapons from World War I of the Belgian Defence. METHODS: Seventeen NIOSH level B-equipped plant workers exposed to arsenic trichloride (AsCl(3)) in combination with phosgene or hydrogen cyanide (HCN) were compared to 24 NIOSH level C-protected field workers occasionally exposed to genotoxic chemicals (including AsCl(3)-phosgene/HCN) when collecting chemical ammunition, and 19 matched referents. Chromosomal aberrations (CA), micronuclei (MNCB and MNMC), sister chromatid exchanges (SCE) and high frequency cells (HFC) were analysed in peripheral blood lymphocytes. Urinary arsenic levels and genetic polymorphisms in major DNA repair enzymes (hOGG1(326), XRCC1(399), XRCC3(241)) were also assessed. RESULTS: SCE and HFC levels were significantly higher in plant-exposed versus referent subjects, but MNCB and MNMC were not different. MNCB, SCE and HFC levels were significantly higher and MNMC levels significantly lower in field-exposed workers versus referents. AsCl(3) exposure was not correlated with genotoxicity biomarkers. CONCLUSIONS: Protective measures for plant-exposed workers appear adequate, but protection for field-exposed individuals could be improved. PMID- 20306074 TI - Langenbeck's Archives and the early development of vascular surgery in Germany. AB - Langenbeck's Archives of Surgery and its predecessor Archiv fur Klinische Chirurgie have addressed vascular surgical problems from the early beginning. In 1860, Bernhard von Langenbeck published a review on venous injuries during tumor surgery, and in 1907, Erich Lexer heralded the era of vascular reconstructive therapy in Germany when he treated an axillary aneurysm by use of a segment of the longer saphenous vein. The Archiv fur Klinische Chirurgie has significantly promoted the development of vascular surgery in Germany especially at the end of the nineteenth and first decades of the twentieth century. PMID- 20306075 TI - The development of trauma, reconstructive, and orthopedic surgery mirrored in Langenbeck's Archives. AB - INTRODUCTION: Reports about trauma and orthopedic surgical procedures are frequently found in the issues of Archiv fur Klinische Chirurgie in the second half of the nineteenth century. Trauma surgery was, on the very beginning of surgery, a case-based, individual treatment with a high risk of wound infection. Today, trauma surgery is a multidisciplinary management. Patients with polytrauma are primarily cared for by trauma surgeons but in cooperation with reconstructive and plastic surgeons and rehabilitation and social workers. DISCUSSION: The German law for trauma insurance (DGUV) was an important step to finance and organize the multidisciplinary care of patients suffering physical trauma. The Swiss AO working group for osteosynthesis evolved a standardization of a worldwide-accepted protocol of surgical management of broken bones. The unification of trauma and orthopedic surgery will result in further progress in the acute and long-term management of trauma patients. PMID- 20306076 TI - Glutathione peroxidase 1 protects mitochondria against hypoxia/reoxygenation damage in mouse hearts. AB - Glutathione peroxidase 1 (GPx1) plays an important role in preventing cardiac dysfunction following ischemia-reperfusion injury. However, its role in protecting cardiac mitochondria against reoxygenation-induced reactive oxygen species (ROS) generation in vivo is unclear. We examined the role of GPx1 in protecting cardiac mitochondria against hypoxia-reoxygenation (HR) damage by testing for alterations in cardiac mitochondrial function. We used a two dimensional gel electrophoresis proteomics analysis to examine the effects of reoxygenation on cardiac protein in wild-type (GPx1(+/+)) and GPx1 knockout (GPx1(-/-)) mouse hearts. We identified 42 protein spots showing differential expression in the two groups. Sixteen of the proteins identified were located in mitochondria and were involved in a number of key metabolic pathways. To verify our proteomics findings functionally, we performed NADH autofluorescence measurements and ATP production assays. The reduced expression of oxidative phosphorylation proteins in GPx1(-/-) mice following HR treatment resulted in loss of the mitochondrial membrane potential and decreased mitochondrial respiration. Mitochondrial ROS production and oxidative mtDNA damage were increased markedly during reoxygenation in GPx1(-/-) hearts. We also found morphological abnormalities in cardiac mitochondria and myocytes in HR-treated GPx1(-/-). This is the first report of the role of GPx1 in protecting cardiac mitochondria against reoxygenation damage in vivo. These findings will help clarify the mechanisms of HR injury and will aid in the development of antioxidant therapies to prevent cardiac mitochondrial dysfunction associated with reoxygenation. PMID- 20306077 TI - Magnetic resonance imaging of the fetal efferent lacrimal pathways. AB - OBJECTIVE: To study the prenatal development of the efferent lacrimal pathways with magnetic resonance imaging (MRI), with special reference to the pathogenesis of congenital dacryocystoceles (CDCCs). METHODS: A total of 751 MRI studies of singleton fetuses [19-40 gestational weeks (GW)] were retrospectively evaluated. Visibility of the efferent lacrimal pathways was assessed on high-resolution T2 weighted sequences and the maximum transverse lacrimal sac diameter was recorded. RESULTS: Fluid-filled lacrimal sacs/nasolacrimal ducts could be demonstrated in 31.7% of fetuses, either unilaterally (50.6%) or bilaterally (49.4%). Visualization was age-dependent: demonstration frequency increased from 24 to 32 GW (60%) and decreased until term. Lacrimal sac diameters varied between 1.9 and 10.5 mm, but showed no correlation with gestational age. Lacrimal sacs with diameters >5 mm were considered to represent CDDC and were found in 2.76% of third-trimester fetuses. CONCLUSION: Fluid-filled efferent lacrimal pathways are a normal finding depending on gestational age. Visualization reflects the effect of two processes that occur over a protracted period of time: opening of the eyelids and lacrimal puncta, and the opening of the Hasner's membrane. Establishing the normal dimensions of the relatively large fetal lacrimal sacs allowed CDCC to be defined and showed a 2.76% incidence of CDCC in third trimester fetuses. PMID- 20306078 TI - Quantitative assessment of stenosis severity and atherosclerotic plaque composition using 256-slice computed tomography. AB - OBJECTIVE: To quantitatively estimate lumen narrowing and to assess the volume and composition of atherosclerotic plaque with 256-slice computed tomography angiography (CTA), using conventional quantitative coronary angiography (QCA) as the gold standard. METHODS: Twenty-seven consecutive patients with suspected coronary artery disease (CAD) underwent 256-slice CTA and subsequent coronary angiography within 4 weeks. Quantification of lumen narrowing was performed on curved multiplanar reformatted CTA images, in identical projections to those used for QCA. Atherosclerotic plaque volume and composition were assessed by using commercially available software. RESULTS: The overall correlation between the stenosis severity by QCA compared with CTA was high (r(2) = 0.79, p < 0.001). For the detection of >or=50% and >or=75% diameter lesions, CTA yielded high sensitivity, specificity and accuracy (86%, 95% and 90%; and 89%, 100% and 96%, respectively), using QCA as the standard reference. Furthermore, assessment of atherosclerotic plaque yielded highly reproducible results (inter-observer and intra-variability of 13% and 9%, respectively, for the assessment of plaque volume, and high agreement between observers (kappa = 0.86) for the differentiation between non-calcified, mixed and calcified plaque). CONCLUSIONS: Clinically indicated 256-slice CT angiography in symptomatic patients can aid both quantification of lumen narrowing and evaluation of atherosclerotic plaque, with high reproducibility. PMID- 20306079 TI - Biphasic contrast medium injection in cardiac CT: moderate versus high concentration contrast material at identical iodine flux and iodine dose. AB - OBJECTIVE: To prospectively investigate the influence of contrast material concentration on enhancement in cardiac CT by using a biphasic single-injection protocol. METHODS: Sixty-four-row multidetector cardiac CT angiography was performed in 159 patients randomised to a moderate or high contrast medium concentration. Contrast material injection included a first phase for enhancement of the coronary arteries and a second phase, at half the iodine flux, targeted at enhancement of the right ventricle. Contrast medium injection was followed by a saline flush. For both concentrations, injection duration (and thus total iodine dose) was adapted to the duration of the CT data acquisition and iodine flux was adjusted to patient weight. Attenuation was measured at various levels in the heart and vessels and the two concentrations compared, overall and per weight group. RESULTS: Enhancement of the aorta and left ventricle was significantly greater with the moderate than with the high concentration contrast medium. This remained true for the two higher weight groups. No difference was found in the lowest weight group or in the right ventricle and pulmonary outflow tract. CONCLUSION: With a biphasic injection protocol, enhancement of the aorta and left ventricle was weaker with the higher concentration of contrast material. PMID- 20306080 TI - MR-guided liver tumor ablation employing open high-field 1.0T MRI for image guided brachytherapy. AB - OBJECTIVE: To determine the feasibility and safety of image-guided brachytherapy employing a modified open high-field MR system. METHODS: This is a follow-up study of a development project enabling technologies for interventional use of 1.0T open MRI. Modifications included coils and in-bore visualization, fluoroscopic sequences and user interfaces. We recruited 104 patients with 224 liver malignancies to receive MR-guided brachytherapy. Interventions were performed >20 min after Gd-EOB-DTPA. We recorded interventional parameters including the intervention time (from acquisition of the first scout until the final sequence for brachytherapy treatment planning). Two reviewers assessed MR fluoroscopic images in comparison to plain CT as used in CT intervention, applying a rating scale of 1-10. Statistical analysis included Friedman and Kendall's W tests. RESULTS: We employed freehand puncture with interactive dynamic imaging for navigation. Technical success rate was 218 complete ablations in 224 tumours (97%). The median intervention time was 61 min. We recorded no adverse events related to the use of MRI. No major complications occurred. The rate of minor complications was 4%. Local control at 3 months was 96%. Superiority of MR-fluoroscopic, Gd-EOB-DTPA-enhanced images over plain CT was highly significant (P < 0.001). CONCLUSION: MR-guided brachytherapy employing open high-field MRI is feasible and safe. PMID- 20306081 TI - A new computer-aided diagnostic tool for non-invasive characterisation of malignant ovarian masses: results of a multicentre validation study. AB - OBJECTIVES: To prospectively assess an innovative computer-aided diagnostic technology that quantifies characteristic features of backscattered ultrasound and theoretically allows transvaginal sonography (TVS) to discriminate benign from malignant adnexal masses. METHODS: Women (n = 264) scheduled for surgical removal of at least one ovary in five centres were included. Preoperative three dimensional (3D)-TVS was performed and the voxel data were analysed by the new technology. The findings at 3D-TVS, serum CA125 levels and the TVS-based diagnosis were compared with histology. Cancer was deemed present when invasive or borderline cancerous processes were observed histologically. RESULTS: Among 375 removed ovaries, 141 cancers (83 adenocarcinomas, 24 borderline, 16 cases of carcinomatosis, nine of metastases and nine others) and 234 non-cancerous ovaries (107 normal, 127 benign tumours) were histologically diagnosed. The new computer aided technology correctly identified 138/141 malignant lesions and 206/234 non malignant tissues (98% sensitivity, 88% specificity). There were no false negative results among the 47 FIGO stage I/II ovarian lesions. Standard TVS and CA125 had sensitivities/specificities of 94%/66% and 89%/75%, respectively. Combining standard TVS and the new technology in parallel significantly improved TVS specificity from 66% to 92% (p < 0.0001). CONCLUSIONS: Computer-aided quantification of backscattered ultrasound is a highly sensitive for the diagnosis of malignant ovarian masses. PMID- 20306082 TI - Lung nodule volumetry: segmentation algorithms within the same software package cannot be used interchangeably. AB - OBJECTIVE: We examined the reproducibility of lung nodule volumetry software that offers three different volumetry algorithms. METHODS: In a lung cancer screening trial, 188 baseline nodules >5 mm were identified. Including follow-ups, these nodules formed a study-set of 545 nodules. Nodules were independently double read by two readers using commercially available volumetry software. The software offers readers three different analysing algorithms. We compared the inter observer variability of nodule volumetry when the readers used the same and different algorithms. RESULTS: Both readers were able to correctly segment and measure 72% of nodules. In 80% of these cases, the readers chose the same algorithm. When readers used the same algorithm, exactly the same volume was measured in 50% of readings and a difference of >25% was observed in 4%. When the readers used different algorithms, 83% of measurements showed a difference of >25%. CONCLUSION: Modern volumetric software failed to correctly segment a high number of screen detected nodules. While choosing a different algorithm can yield better segmentation of a lung nodule, reproducibility of volumetric measurements deteriorates substantially when different algorithms were used. It is crucial even in the same software package to choose identical parameters for follow-up. PMID- 20306083 TI - A case report of a normal aorta misdiagnosed as type A dissection by modern multidetector computed tomography. AB - Computed tomography (CT) is generally considered the investigation of choice to exclude acute aortic syndrome. We report an important potentially disastrous misdiagnosis using a modern 32 slice multidetector CT system. PMID- 20306084 TI - Combined correction of recovery effect and motion blur for SUV quantification of solitary pulmonary nodules in FDG PET/CT. AB - OBJECTIVE: We evaluate a fully data-driven method for the combined recovery and motion blur correction of small solitary pulmonary nodules (SPNs) in F-18 fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT). METHODS: The SPN was segmented in the low-dose CT using a variable Hounsfield threshold and morphological constraints. The combined effect of limited spatial resolution and motion blur in the SPN's PET image was then modelled by an effective Gaussian point-spread function (psf). Both isotropic and non-isotropic psfs were used. To validate the method, PET/CT measurements of the NEMA/IEC spheres phantom were performed. The method was applied to 50 unselected SPNs or=30%) SUV increase in 47 SPNs (94%). CONCLUSIONS: Correction of both recovery and motion blur is mandatory for accurate SUV quantification of SPNs. PMID- 20306085 TI - Treatment of carotid siphon aneurysms by use of the Willis stent graft: an angiographic and histopathological study. AB - OBJECTIVE: We designed a carotid siphon (CS) aneurysm model in dogs to test a new stent graft (the Willis covered stent) and compared tissue reaction over 12-month follow-up versus a comparison group with stents implanted in straight vessels. METHODS: Twenty-four saccular sidewall aneurysms (group A) and 12 CS aneurysms (group B) were created surgically. A Willis stent graft was implanted in each aneurysm. Angiography was performed immediately and at 1-, 3-, 6- and 12-month post-implantation to investigate aneurysm isolation, endoleak, stent angulation, parent artery (PA) patency and restenosis. Light and scanning electron microscopy were used to identify aneurysmal sac thrombi, intima hyperplasia and endothelial progress. RESULTS: Immediate angiography demonstrated mild endoleak in two aneurysms and three stent angulations in group B. Follow-up at 12 months revealed resolved endoleaks, occlusion in one PA and mild stenosis in three in group B. In group A, occlusion occurred in one PA and mild stenosis in two. Light microscopy revealed new intima, and all aneurysm sacs were filled with thrombi. In group B, endothelial progress was complete at 12 months, and closely correlated with haemodynamic changes. CONCLUSIONS: Application of a Willis stent graft is a feasible method of treating CS aneurysms, and it exhibits a prolonged endothelial progress compared with that in straight vessels. PMID- 20306086 TI - Considerations on the mechanisms of alveolar remodeling in centriacinar emphysema. AB - Chronic obstructive pulmonary disease is mainly characterized by irreversible airflow limitation, and its major pathological change is alveolar destruction and enlargement, which induces emphysema. In this study, we used stereoscopic microscopy to observe the cut surfaces of 21 surgically resected or autopsied lungs showing centriacinar emphysema. We identified columnar structures of various sizes in the cystic spaces. These columnar structures constituted two types: one that was associated with pulmonary artery and another that was not. We examined these structures in detail by light microscopy and performed statistical analyses. Columnar structures without pulmonary artery showed destruction and accumulation of alveoli, including abnormally aggregated elastic fibers. In contrast, pulmonary architecture was preserved in columnar structures with pulmonary artery. In columnar structures without pulmonary artery, statistically significant correlations were observed between the thickness of columnar structures and size of centriacinar cystic spaces and between the thickness of columnar structures and aggregation of elastic fibers in columnar structures. Electron microscopy showed that the columns were composed of aggregated elastic fibers, collagen fibers, mesenchymal cells, pigmented macrophages, and the alveolar epithelial cells covering them. Immunohistochemistry showed that the aggregated elastic fibers were positive for alpha-1 antitrypsin. We concluded that columnar structures without pulmonary artery are a hallmark of alveolar wall destruction seen in pulmonary emphysema. PMID- 20306088 TI - High FDG uptake in PET/CT predicts worse prognosis in patients with metastatic gastric adenocarcinoma. AB - PURPOSE: We evaluated the role of FDG-PET/CT in patients with metastatic gastric adenocarcinoma before palliative chemotherapy to predict prognosis and chemotherapeutic response. METHODS: The study included 35 consecutive newly diagnosed patients with metastatic gastric adenocarcinoma who underwent FDG PET/CT before palliative chemotherapy. Maximum standardized uptake value (SUVmax) of the primary tumor was assessed to evaluate survival and chemotherapeutic response. Survival analysis was performed for time to progression and overall survival using the Kaplan-Meier method. Cox proportional hazard models were used to determine independent prognostic factors. RESULTS: All primary tumors were visualized using FDG-PET/CT (mean SUVmax = 8.1 +/- 4.5, range 2.5-22.1). Sensitivity, specificity, and accuracy of FDG-PET/CT in detection of solid organ metastasis were 95.2% (20/21), 100% (14/14), and 97.1% (34/35), respectively. No significant difference of primary tumor SUVmax was found among the chemotherapeutic response groups. Univariate survival analysis demonstrated ECOG performance status (>=2), presence of solid organ metastasis, number of organs involved in distant metastasis (>=2), and SUVmax of the primary tumor (>8) as significant predictors for poor overall survival. Multivariate survival analysis showed SUVmax of the primary tumor (P = 0.048), presence of solid organ metastasis (P = 0.015), and ECOG performance status (P = 0.002) as significant independent prognostic predictors for overall survival. CONCLUSIONS: High FDG uptake of the primary tumor in patients with metastatic gastric adenocarcinoma is associated with poor overall survival. Assessment of tumor FDG uptake has limited value for prediction of chemotherapeutic response, but provides useful information regarding prognosis. PMID- 20306087 TI - Second primary esophageal or lung cancer in patients with head and neck carcinoma in Taiwan: incidence and risk in relation to primary index tumor site. AB - BACKGROUND: Second primary cancer is prevalent in patients with head and neck cancer (HNC), for which esophagus and lung are the most usual sites, associated with an extremely poor prognosis. However, information regarding the actual risk of second primary esophageal or lung cancer in South-east Asia, the betel-quid chewing area, has been restricted to data from single-institutions. We have therefore conducted a population-based study to evaluate the incidence, risk, and developmental time of second esophageal or lung cancer in HNC patients. METHODS: Standardized incidence ratios (SIRs) and cumulative incidences were calculated for second primary esophageal or lung cancer using a database from the Taiwan Cancer Registry that included 63,720 cases having an initial diagnosis of HNC. RESULTS: The risk of second esophageal cancer was increased in patients with oral/pharyngeal (SIR = 8.71, 95% CI 7.55-10.01) and laryngeal (SIR = 4.65, 95% CI 3.37-6.27) cancers, whereas second lung risk was increased in patients with laryngeal (SIR = 2.05, 95% CI 1.69-2.45) and oral/pharyngeal (SIR = 1.56, 95% CI 1.34-1.80) cancers. The risk excess was prominent for patients with a follow-up interval <5 years and a first primary cancer diagnosed at age <50. Nevertheless, patients with nasopharyngeal carcinoma were not associated with an excess risk in second esophageal or lung cancer. CONCLUSIONS: The present dataset provides definite evidence that there is a substantial excess risk of second primary esophageal or lung cancer for the index tumors of oral cavity, pharynx and larynx. The absence of risk excess found in nasopharyngeal carcinoma is also compatible with the existing knowledge that it might have an entirely distinctive etiology. PMID- 20306089 TI - Juvenile rheumatoid arthritis with focal segmental glomerulosclerosis: a rare association. PMID- 20306090 TI - Systematic reviews of oral complications from cancer therapies, Oral Care Study Group, MASCC/ISOO: methodology and quality of the literature. AB - BACKGROUND: Oral complications are commonly experienced by patients undergoing cancer therapies. The Oral Care Study Group of the Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology (MASCC/ISOO) has completed nine systematic reviews including Bisphosphonate Osteonecrosis of the Jaw, Odontogenic/Periodontal Infection, Dysgeusia, Oral Fungal Infection, Osteoradionecrosis, Trismus, Oral Pain, Oral Viral Infection, and Xerostomia. METHODS: The aims of these reviews were to determine the prevalence of each oral complication, relationship with quality of life, economic impact, and formulation of guidelines based on the quality of the literature. The present article described the details of the methodology and statistical analysis utilized in these nine systematic reviews. Additionally, a summary of the quality of the literature from these oral complications is presented. CONCLUSION: Oral complications associated with cancer therapies are common among cancer patients. The systematic reviews by the Oral Care Study Group of MASCC/ISOO provide a thorough assessment of the available literature for these oral complications. PMID- 20306091 TI - Simulation-based training improves applied clinical placement of ultrasound guided PICCs. AB - PURPOSE: Skilled placement of peripherally inserted central catheters (PICC) has a profound impact on patient well-being and costs of care. The use of ultrasound guided methods and prescribed training for cannulation skills are evidence-based practice recommendations. The purpose of this study was to compare two methods of PICC instruction on the acquisition of applied skills. METHODS: Residents were randomly assigned to one of two groups (N = 16/16) of this blind-rater study and were trained to perform ultrasound-guided PICC cannulation using either simulation or apprenticeship methods. All residents were assessed placing a PICC in applied clinical patient care. RESULTS: Residents who completed simulation training had significantly better transfer of skills to applied clinical practice than residents who received apprenticeship training, having better performance ratings on eight of nine procedure-specific task measures (p < 0.05) and higher success rates in endpoint PICC placement. CONCLUSIONS: These results support the use of prescribed simulation-based training for the acquisition of requisite skills associated with PICC placement and expand on similar studies that suggest the advantages of simulation-based training for central line placement. Additionally, the data suggest that training using a single simulation model may support the acquisition of both central venous catheterization and PICC skills. PMID- 20306092 TI - Risk factors for chemotherapy-induced neutropenia occurrence in breast cancer patients: data from the INC-EU Prospective Observational European Neutropenia Study. AB - BACKGROUND: Chemotherapy-induced neutropenia (CIN) places patients at risk of life-threatening infections. While reduction of chemotherapy dose or delay of the subsequent treatment cycle and, consequently, reduction of relative dose intensity (RDI) may limit myelotoxicity, these actions can also impact adversely on treatment outcome and should be avoided in adjuvant settings. PATIENTS AND METHODS: Based on data from 444 breast cancer patients in the INC-EU Prospective Observational European Neutropenia Study, we have evaluated patient-specific and treatment-specific factors that impact on the incidence of grade 4 CIN (absolute neutrophil count <0.5 * 10(9)/L), either during the first or in any cycle of (neo)adjuvant chemotherapy, across a range of regimens and doses. RESULTS: Using multivariate logistic regression analysis, risk factors for grade 4 CIN were identified as older age, lower weight, higher planned dose intensity of doxorubicin, epirubicin, or docetaxel, higher number of planned cycles, vascular comorbidity, lower baseline white blood cell count, and higher baseline bilirubin. Use of colony-stimulating factor before a neutropenic event occurred, dose delays, and dose reductions were protective against grade 4 CIN. CONCLUSIONS: By identifying risk factors for grade 4 CIN, CSF prophylaxis may be appropriately targeted to prevent low RDI in patients treated with curative intent. PMID- 20306093 TI - Knotting of two central venous catheters: a rare complication of pulmonary artery catheterization. PMID- 20306094 TI - Do Cecidomyiidae galls of Aspidosperma spruceanum (Apocynaceae) fit the pre established cytological and histochemical patterns? AB - Cecidomyiidae galls commonly present a zonation of tissues with lignified cell layers externally limiting a reserve tissue and internally limiting a specialized nutritive tissue next to the larval chamber. The cytological aspects of this specialized tissue indicate high metabolic activity as well as carbohydrate accumulation. In Aspidosperma spruceanum-Cecidomyiidae gall system, ultrastructural and histochemical investigations corroborated this pattern and also revealed the storage of proteins in the nutritive cells. Reactive oxygen species (ROS), callose, and pectin accumulation were related to the feeding activity of the galling herbivore. Phosphorylase, glucose-6-phosphatase, acid phosphatases, invertases, and sucrose synthase activities were detected for the first time, in the Neotropical region, and discussed in relation to gall maintenance and the feeding activity of the Cecidomyiidae. PMID- 20306095 TI - Asymmetric synthesis of enantiomerically and diastereoisomerically enriched 4-[F or Br]-substituted glutamic acids. AB - A novel simple synthetic protocol for the preparation of both (2S,4R)- and (2S,4S)-FGlu, applying Michael addition of methyl alpha-fluoroacrylate to a NiII complex of glycine Schiff base with BPB, was elaborated. In addition, same reaction of mentioned complex with ethyl alpha-bromoacrylate leads to the NiII complex of the Schiff base of BPB with (2S,4R)-4-bromo-glutamic acid monoester, that can be transformed into the corresponding complexes of 1-aminocyclopropane 1,2-dicarboxylic acid. The decomposition of the diastereoisomerically pure complexes leads to corresponding enantiomerically enriched (ee>98%) amino acids. PMID- 20306096 TI - The role of zinc in the S100 proteins: insights from the X-ray structures. AB - We here aim to summarise the present knowledge on zinc binding by S100 proteins. While the importance of modulation of the function of the S100 family of EF-hand proteins by calcium is well established, a substantial proportion is also regulated by zinc or copper. Indeed regulation by zinc in addition to calcium was suggested almost as soon as the first S100 protein was discovered and has been confirmed for many family members by numerous experiments. For the first, "His Zn", group, zinc-binding sites composed of three histidines and an aspartic acid were first proposed based on sequence comparisons and later confirmed by structural studies. A second, "Cys-Zn", group lacks such well-defined zinc binding motifs and for these cysteines were suggested as the main zinc ligands. There is no three-dimensional structure for a Cys-Zn S100 in the presence of zinc. However, analysis of their sequences together with their X-ray structures in the absence of zinc suggests the possibility of two zinc-binding sites: a conserved site with a degree of similarity to those of the His-Zn group and a less-defined site with a Cys interdimer-binding motif. Some S100 protein-mediated events, such as signalling in the extracellular space, where the levels of calcium are already high, are most unlikely to be calcium regulated. Therefore, a broader knowledge of the role of zinc in the functioning of the S100 proteins will add significantly to the understanding how they propagate their signals. PMID- 20306097 TI - Expression systems of human beta-defensins: vectors, purification and biological activities. AB - Human beta-defensins are 2-5 kDa, cationic, microbicidal peptides, which represent the first-line host defense against several Gram-negative and Gram positive bacteria, fungi and viruses. They contain a conserved disulfide-bridge pattern of three pairs of intramolecular cystine bonds. The well-known public health problem related with the growing number of multiresistant bacteria has driven research to look for novel antibiotics, such beta-defensins and a feasible way to produce them. Heterologous expression of beta-defensins could be one way to generate large quantities of beta-defensins for clinical research; however, heterologous expression of beta-defensins has some biochemical problems, such toxicity toward the host cell, peptide degradation by proteolytic cell enzymes, size, folding constrains and low recombinant peptide yields. In this communication, several heterologous systems for producing human beta-defensins are reviewed. PMID- 20306098 TI - Ink-jet printout of radiographs on transparent film and glossy paper versus monitor display: an ROC analysis. AB - The aim of this study was to compare the depiction ability of small grayscale contrasts in ink-jet printouts of digital radiographs on different print media with CRT monitor. A CCD-based digital cephalometric image of a stepless aluminum wedge containing 50 bur holes of different depth was cut into 100 isometric images. Each image was printed on glossy paper and on transparent film by means of a high-resolution desktop inkjet printer at specific settings. The printed images were viewed under standardized conditions, and the perceptibility of the bur holes was evaluated and compared to the perceptibility on a 17-in CRT monitor. Thirty observers stated their blinded decision on a five-point confidence scale. Areas (Az) under receiver operating characteristics curves were calculated and compared using the pair wise sign tests. Overall agreement was estimated using Cohen's kappa device and observer bias using McNemar's test. Glossy paper prints and monitor display revealed significantly higher (P < 0.001) average Az values (0.83) compared to prints on transparent film (0.79), which was caused by higher sensitivity. Specificity was similar for all modalities. The sensitivity was dependent on the mean gray scale values for the transparent film. PMID- 20306100 TI - Theoretical studies on identity S(N)2 reactions of lithium halide and methyl halide: a microhydration model. AB - Reactions of lithium halide (LiX, X = F, Cl, Br and I) and methyl halide (CH3X, X = F, Cl, Br and I) have been investigated at the B3LYP/6-31G(d) level of theory using the microhydration model. Beginning with hydrated lithium ion, four or two water molecules have been conveniently introduced to these aqueous-phase halogen exchange S(N)2 reactions. These water molecules coordinated with the center metal lithium ion, and also interacted with entering and leaving halogen anion via hydrogen bond in complexes and transition state, which to some extent compensated hydration of halogen anion. At 298 K the reaction profiles all involve central barriers DeltaE ( cent ) which are found to decrease in the order F > Cl > Br > I. The same trend is also found for the overall barriers (DeltaE(ovr)) of the title reaction. In the S(N)2 reaction of sodium iodide and methyl iodide, the activation energy agrees well with the aqueous conductometric investigation. PMID- 20306099 TI - Experimental study determining the mechanical properties of dental floss holders. AB - This study determined the mechanical properties of 19 dental floss holders. Eight single-use holders and 11 reusable ones were tested. An in vitro model with dental proximal contact strength of 8 N was created. Every device had to pass the proximal contact 30 times. We measured (1) the displacement of the floss [mm], (2) the force [N] necessary to pass the proximal contact after the 30th passage, (3) the loosening of the floss (offset [mm]), and (4) the change in the distance between the branches [mm]. Each measurement was repeated seven times. The results are displacement of the floss after 30 passages, 2.0 to 9.2 mm; passage force, 2.6 to 11 N; increases in branch distance, 0-2.9 mm; offset of the floss, 0-1.8 mm (all numbers are medians). Based on cleaning a full dentition (30 passages), we suggest introducing minimal requirements of <4 mm for the displacement of the floss, >=11 N for the force, and <0.1 mm for the difference in branch distance and the offset. Only two products fulfilled our criteria. The tests show that dental floss holders vary extremely in their mechanical properties. Their effective use seems often impossible due to limited mechanical properties. PMID- 20306102 TI - Do apes know that they could be wrong? AB - When confronted with uncertain or incomplete information in decision-making situations, monkeys and apes opt for either escaping the situation or seeking additional information. These responses have been interpreted as evidence of metacognitive abilities. However, this interpretation has been challenged. On the one hand, studies using the information-seeking paradigm have been criticized because subjects may simply engage in a search for information routine (e.g., search until spot the reward) without any metacognitive involvement. On the other hand, studies using the escape response paradigm have been criticized because subjects may not recognize their own state of uncertainty but have learned to use the escape response in the presence of certain stimuli configurations that create uncertainty. The current study attempted to address these two criticisms by presenting great apes (seven gorillas, eight chimpanzees, four bonobos, seven orangutans) with a seeking information task whose basic procedure consisted of presenting two hollow tubes, baiting one of them and letting subjects choose. Conditions varied depending on whether subjects had visual access to the baiting, the cost associated with seeking information, the time interval between baiting and choosing, the food quality and the additional information offered regarding the food's location. Although subjects showed a high retrieval accuracy when they had witnessed the baiting, they were more likely to check inside the tube before choosing when high stakes were involved (Experiment 3) or after a longer period of time had elapsed between the baiting and the retrieval of the reward (Experiment 2). In contrast, providing subjects with indirect auditory information about the food's location or increasing the cost of checking reduced checking before choosing (Experiment 1). Taken together, these findings suggest that subjects knew that they could be wrong when choosing. PMID- 20306101 TI - Perception of improvement after orthognathic surgery: the important variables affecting patient satisfaction. AB - PURPOSE: We evaluated which factors affect patient satisfaction and if patient expectations were fulfilled after orthognathic surgery. METHODS: Questionnaires consisting of 14 questions were given 1 year after bimaxillary osteotomy for class-III correction to subjects. Six questions were answered using an 11-point rating scale based on a visual analog scale (VAS; 0 = poor; 10 = excellent). Also included were seven closed-form questions with yes/no answers, as well as one open question for 'further remarks'. Sagittal and vertical cephalometric parameters were determined on postoperative cephalograms. RESULTS: Seventy-seven patients (37 females, 40 males; mean age, 23.4 +/- 4.9 (SD) years) responded. The intention to undergo surgery only for aesthetic improvement was noted in 11.9% of patients; only improvement of chewing function in 15.5%; both in 71.4%; and none/don't know in 2.6%. Postoperative satisfaction was rated (in means) with 8.13 +/- 1.97 on VAS and correlated significantly with the opinions of friends and relatives. Facial aesthetics was rated 5.6 +/- 1.2 before surgery and 8.1 +/- 1.5 after surgery (p = 0.04). Preoperative chewing function was rated 5.65 +/- 1.8 and 8.03 +/- 1.51 after surgery (p = 0.014). TMJ disorders or hypoesthesia had no negative impacts. Cephalometric analyses revealed a significantly lower SNB (75.3 degrees +/- 2.7 degrees ; p = 0.033) in patients rating lower than grade 7 for overall satisfaction. For SNA and ArGoMe, no significant differences were observed. CONCLUSION: The most distinctive factors for patient satisfaction after orthognathic surgery were chewing function and facial aesthetics with respect to the lower face. Function, aesthetics, and even psychological aspects should be considered equally when planning surgery. PMID- 20306103 TI - Elevation of plasma membrane permeability upon laser irradiation of extracellular microbubbles. AB - Laser-mediated gene transfection has received much attention as a new method for targeted gene therapy because of the high controllability of laser energy and direction. In this report, we describe a combination laser-microbubble system that enables membrane-impermeable molecules to penetrate cell membranes. The main theories we apply are optical breakdown and photoacoustic generation, which are induced by laser irradiation. Firstly, different types of laser light (Ar-green, Novus Varia poly-wavelength and Nd:YAG laser) were adopted to blast liposome microbubble contrast medium; subsequently, the Nd:YAG laser (1064 nm, 4 ns), which could successfully blast microbubbles, and ultrasound were used in combination to irradiate a mixture of liposome microbubbles and retinoblastoma (Rb) cells. After irradiation, membrane permeability was evaluated by flow cytometric assay using propidium iodide (PI) and fluorescein diacetate (FDA). The proportion of permeabilized resealed cells was affected by changes in the light energy. All of the Nd:YAG laser, Nd:YAG combination laser-microbubble and combination ultrasound-microbubble systems were able to permeabilize the Rb cells. These results suggest that this combination laser-microbubble system is a new means of delivering exogenous materials into living cells. PMID- 20306104 TI - Can lab data be used to reduce abdominal computed tomography (CT) usage in young adults presenting to the emergency department with nontraumatic abdominal pain? AB - We sought to determine whether laboratory parameters could be found, predictive of a negative abdominal CT scan in young adults with nontraumatic abdominal pain. Following institutional review board approval, we evaluated CT reports of 522 patients, aged 21-35 years old, who presented to the Emergency Department with nontraumatic abdominal pain. Bivariate analyses relating ten laboratory parameters to whether the CT detected a cause for abdominal pain were conducted. A multivariate logistic regression model was then derived, with all variables in the final model significant at p < 0.05. Variables were dichotomized to yield odds ratios and 95% confidence intervals. Of the 522 patients meeting inclusion criteria, 45% had a cause for pain demonstrated by CT. Predictors of a negative CT in men were normal hematocrit and negative urine blood (p = 0.045, p = 0.016, respectively), and in women normal hematocrit, granulocyte percent, and alkaline phosphatase (p = 0.023, p = 0.039, p < 0.0001, respectively). When standard normal values were used to calculate descriptive statistics, only granulocyte percent in women had a significant confidence interval (odds ratio 2.5, confidence interval 1.6-4.0). Among the 208 women with normal granulocyte percent, the final clinical diagnosis was appendicitis, cholecystitis, and diverticulitis, in three, three, and two cases, respectively (4% combined). In summary, no laboratory test was sufficient to offer reassurance that a CT is not necessary in a young adult patient with nontraumatic abdominal pain. Alternative strategies should be considered to decrease the use of CT, and its associated radiation exposure, in young adults with nontraumatic abdominal pain. PMID- 20306105 TI - Far-distant metastases along the CSF pathway of glioblastoma multiforme during continuous low-dose chemotherapy with temozolomide and celecoxib. AB - Glioblastoma multiforme is the most common and most malignant primary brain tumour. Prognosis after diagnosis remains poor despite recent advances in adjuvant therapy. Treatment of choice is gross surgical resection and combined radio-chemotherapy with temozolomide as chemotherapeutic agent. Experimental continuous low-dose chemotherapy with temozolomide in combination with a cyclooxygenase-2 inhibitor has shown encouraging effects on progression-free survival and overall survival in patients, but leads to a high proportion of distant recurrences. Here, we describe extreme far-distant metastases along the neural axis of glioblastoma multiforme in four patients receiving metronomic antiangiogenic chemotherapy and review the literature to discuss possible mechanisms. PMID- 20306106 TI - Urgent open embolectomy for cardioembolic cervical internal carotid artery occlusion. AB - Acute ischemic stroke attributable to cervical internal carotid artery (ICA) occlusion is frequently associated with severe disability or death and is usually caused by atherosclerosis. By contrast, the cardioembolic cervical ICA occlusion is rare, and feasibility of urgent recanalization remains unclear. We present the first study in the literature that focuses on urgent open embolectomy for the treatment of cardioembolic cervical ICA occlusion. A retrospective review of the charts for patients undergoing open embolectomy was performed. Between April 2006 and September 2007, 640 consecutive patients with acute ischemic stroke were treated. Of them, three patients (0.47%) with the acute complete cardioembolic cervical ICA occlusion underwent urgent open embolectomy. All patients presented with profound neurological deficits and atrial fibrillation. The urgent open embolectomy achieved complete recanalization in all patients without any complications. All emboli in three patients were very large and fibrinous in histological findings. Two of three patients showed rapid improvement in neurological functions after surgical treatments. The cardioembolic occlusion of the cervical ICA is rare, but its possibility should be considered in patients with acute ischemic stroke suffering profound neurological deficits and atrial fibrillation. Urgent open embolectomy may be a treatment option to obtain successful recanalization for cardioembolic cervical ICA occlusion and is recommended because it is technically easier and similar to carotid endarterectomy. PMID- 20306107 TI - A case of pandemic 2009 influenza A (H1N1) in a patient with HIV infection. AB - Little is known about pandemic 2009 influenza A (H1N1) among patients with human immunodeficiency virus (HIV) infection. We report a case of 2009 influenza A (H1N1) in a patient who was newly diagnosed as having HIV. His general condition was good, and he was successfully treated in an outpatient setting. The literature was reviewed for the diagnosis, treatment, prevention, and infection control of pandemic 2009 influenza A (H1N1) among those who have HIV infection. PMID- 20306108 TI - Emergence of the community-acquired methicillin-resistant Staphylococcus aureus USA300 clone in a Japanese child, demonstrating multiple divergent strains in Japan. AB - In 2008 we isolated methicillin-resistant Staphylococcus aureus (MRSA) from an 11 month-old Japanese girl who lived in Saitama, Japan, and suffered from cellulitis of the lower thigh and sepsis. The MRSA (strain NN47) belonged to multilocus sequence type (ST) 8 and exhibited spa363 (t024), agr1, staphylococcal cassette chromosome mec (SCCmec) type IVa, and coagulase type III. It was positive for Panton-Valentine leukocidin (PVL) and the arginine catabolic mobile element (ACME). Pulsed-field gel electrophoresis (PFGE) demonstrated that the MRSA was the USA300 clone, which is the predominant community-acquired MRSA (CA-MRSA) in the US. Strain NN47 was divergent, in terms of the spa type and patterns of PFGE and plasmids, from the USA300-0114 type strain or USA300 strain NN36, previously isolated from a visitor (Indian girl) from the US. Strain NN47 was resistant to erythromycin, in addition to beta-lactam agents (e.g., oxacillin). These data demonstrate the first emergence of the USA300 clone in Japanese children who have never been abroad and have had no contact with foreigners (and therefore, the first USA300 spread in Japan), and also emergence of multiple divergent strains of the USA300 clone in Japan. Because the USA300 clone is highly transmissible and virulent, surveillance of the USA300 clone is needed. PMID- 20306109 TI - The costs of breast cancer prior to and following diagnosis. AB - This retrospective incidence-based cost-of-illness analysis aims to quantify the costs associated with female breast cancer in Flanders for the year prior to diagnosis and for each of the 5 years following diagnosis. A bottom-up analysis from the societal perspective included direct health care costs and indirect costs of productivity loss due to morbidity and premature mortality. A case control study design compared total costs of breast cancer patients with costs of an equivalent standardised population with a view to calculating the additional costs that can be attributed to breast cancer. Total average costs of breast cancer amounted to 107,456 per patient over 6 years. Total costs consisted of productivity loss costs (89% of costs) and health care costs (11% of costs). Health care costs did not vary with age at diagnosis. Health care costs of breast cancer patients converged with those of the general population at 5 years following diagnosis. Patients with advanced breast cancer stadia had higher health care costs. Cost estimates provided by this analysis can be used to determine priorities for, and inform, future research on breast cancer. In particular, attention needs to be focussed on decreasing productivity loss from breast cancer. PMID- 20306110 TI - Technical efficiency in primary health care: does quality matter? AB - The accuracy required in the measurement of output is an issue that has as yet still not been satisfactorily addressed in empirical research on efficiency in primary health care. We exploit information retrieved from a newly constructed database (APEX06) for the Spanish region of Extremadura. The richness of our dataset allows us to consider original synthetic measures of output that take into account both the quantity and the quality of services provided by 85 primary care centers (PCCs) in 2006. We provide evidence that neglecting the issue of properly accounting for the quality of health services can lead to misleading results. Our main finding is that adjusting output for quality has a three-fold effect on efficiency analysis. Firstly, inefficiency explains relatively more of the deviation from potential output. Secondly, the average technical efficiency in the sector is lower, while its dispersion among PCCs is significantly higher. Thirdly, the efficiency ranking of the PCCs is affected. PMID- 20306111 TI - The effect of alcoholic beverage excise tax on alcohol-attributable injury mortalities. AB - This study examines the effect of state excise taxes on different types of alcoholic beverages (spirits, wine, and beer) on alcohol-attributable injury mortalities--deaths caused by motor vehicle accidents, suicides, homicides, and falls--in the United States between 1995 and 2004, using state-level panel data. There is evidence that injury deaths attributable to alcohol respond differently to changes in state excise taxes on alcohol-specific beverages. This study examines the direct relationship between injury deaths and excise taxes without testing the degree of the association between excise taxes and alcohol consumption. The study finds that beer taxes are negatively related to motor vehicle accident mortality, while wine taxes are negatively associated with suicides and falls. The positive coefficient of the spirit taxes on falls implies a substitution effect between spirits and wine, suggesting that an increase in spirit tax will cause spirit buyers to purchase more wine. This study finds no evidence of a relationship between homicides and state excise taxes on alcohol. Thus, the study concludes that injury deaths attributable to alcohol respond differently to the excise taxes on different types of alcoholic beverages. PMID- 20306112 TI - Estimates of patient costs related with population morbidity: can indirect costs affect the results? AB - A number of health economics studies require patient cost estimates as basic information input. However, the accuracy of cost estimates remains generally unspecified. We propose to investigate how the allocation of indirect costs or overheads can affect the estimation of patient costs and lead to improvements in the analysis of patient cost estimates. Instead of focussing on the costing method, this paper will highlight observed changes in variation explained by a methodology choice. We compare four overhead allocation methods for a specific Spanish population adjusted using the Clinical Risk Groups model. Our main conclusion is that the amount of global variation explained by the risk adjustment model depends mainly on direct costs, regardless of the cost allocation methodology used. Furthermore, the variation explained can be slightly increased, depending on the cost allocation methodology, and is independent of the level of aggregation in the classification system. PMID- 20306113 TI - Imaging informatics: challenges in multi-site imaging trials. AB - Multi-site imaging research has several specialized needs that are substantially different from what is commonly available in clinical imaging systems. An attempt to address these concerns is being led by several institutes including the National Institutes of Health and the National Cancer Institute. With the exception of results reporting (which has an infrastructure for standard reports, albeit with several competing lexicons), medical imaging has been largely standardized by the efforts of DICOM, HL7, and IHE. What are not well developed in this area are the tools required for multi-site imaging collaboration and data mining. The goal of this paper is to identify existing clinical interoperability methods that can be used to harmonize the research and clinical worlds, and identify gaps where they exist. To do so, we will detail the approaches of a specific multi-site trial, point out the current deficiencies and workarounds developed in that trial, and finally point to work that seeks to address multi site imaging challenges. PMID- 20306115 TI - Effects of feedback from active and passive body parts on spatial and temporal parameters in sensorimotor synchronization. AB - Previous research on sensorimotor synchronization has manipulated the somatosensory information received from the tapping finger to investigate how feedback from an active effector affects temporal coordination. The current study explored the role of feedback from passive body parts in the regulation of spatiotemporal motor control parameters by employing a task that required finger tapping on one's own skin at anatomical locations of varying tactile sensitivity. A motion capture system recorded participants' movements as they synchronized with an auditory pacing signal by tapping with the right index finger on either their left index fingertip (Finger/Finger) or forearm (Finger/Forearm). Results indicated that tap timing was more variable, and movement amplitude was larger and more variable, when tapping on the finger than when tapping on the less sensitive forearm. Finger/Finger tapping may be impaired relative to Finger/Forearm tapping due to ambiguity arising through overlap in neural activity associated with tactile feedback from the active and the passive limb in the former. To compensate, the control system may strengthen the assignment of tap-related feedback to the active finger by generating correlated noise in movement kinematics and tap dynamics. PMID- 20306114 TI - Control of death receptor ligand activity by posttranslational modifications. AB - The death receptor ligands are involved in many physiological and pathological processes involving triggering of apoptosis, inflammation, proliferation, and activation. The expression of these molecules is reported to be tightly regulated at the transcriptional level. However, over the last few years, an increasing number of data demonstrated that the control of transcription is only one of the mechanisms that manage the expression of the death receptor ligands. Thus, this review is focused on posttranslational regulation of the three main members of this family, namely FasL, TNF-alpha, and TRAIL. We discuss here the importance of distribution, storage, and degranulation of these molecules, as well as their shedding by proteases on the control of death receptor ligands expression and activity. PMID- 20306116 TI - Phase II trial of S-1 monotherapy in elderly or frail patients with metastatic colorectal cancer. AB - A phase II study was conducted to evaluate S-1 monotherapy in previously untreated elderly or frail metastatic colorectal cancer patients. A total of 48 elderly (70-85 years old) and frail [Eastern Cooperative Oncology Group (ECOG) performance status (PS) 2 and 65-69 years old] patients were eligible for first line S-1 of 35 mg/m(2) given twice daily for 2 weeks followed by 1 week of rest. The overall response rate (ORR) for all patients was 19%. Similarly, the ORR for frail and elderly patients was 22% and 18%, respectively. Median progression-free survival (PFS) and overall survival (OS) for all patients were 3.9 months (95% CI, 3.0-4.8) and 11.3 months (95% CI, 7.4-15.2), respectively. For frail patients, PFS was 1.4 (95% CI, 0.8-2.0) vs. 4.3 months (95% CI, 3.0-5.4) for the elderly (P = 0.016). OS was significantly longer for elderly patients than for frail patients (13.1 months, 95% CI, 9.5-16.7) vs. (4.1 months, 95% CI, 3.2-5.0; P = 0.01). Toxicity was mild to moderate, as only 29% of patients experienced grade 3 toxicity. Grade 4 toxicity and febrile neutropenia did not occur; however, two frail patients died from grade 5 treatment-related infections. Generally, S-1 monotherapy was well-tolerated and efficacious in the elderly patient group, but not in the frail patient group. Considering performance status and co-morbidities in patients >70 years old, S-1 monotherapy may be a first-line therapeutic option for elderly mCRC patients. PMID- 20306117 TI - Broadband 15N-13C dipolar recoupling via symmetry-based RF pulse schemes at high MAS frequencies. AB - An approach for generating efficient NR(vS, vk)(n) symmetry-based dual channel RF pulse schemes for gamma-encoded broadband (15)N-(13)C dipolar recoupling at high magic angle spinning frequencies is presented. The method involves the numerical optimisation of the RF phase-modulation profile of the basic "R" element so as to obtain heteronuclear double quantum dipolar recoupling sequences with satisfactory magnetisation transfer characteristics. The basic "R" element was implemented as a sandwich of a small number of short pulses of equal duration with each pulse characterised by a RF phase and amplitude values. The performance characteristics of the sequences were evaluated via numerical simulations and (15)N-(13)C chemical shift correlation experiments. Employing such (13)C-(15)N double-quantum recoupling sequences and the multiple receiver capabilities available in the current generation of NMR spectrometers, the possibility to simultaneously acquire 3D NCC and CNH chemical shift correlation spectra is also demonstrated. PMID- 20306118 TI - Analysis of transgenic wheat (Triticum aestivum L.) harboring a maize (Zea mays L.) gene for plastid EF-Tu: segregation pattern, expression and effects of the transgene. AB - We previously reported that transgenic wheat (Triticum aestivum L.) carrying a maize (Zea mays L.) gene (Zmeftu1) for chloroplast protein synthesis elongation factor, EF-Tu, displays reduced thermal aggregation of leaf proteins, reduced injury to photosynthetic membranes (thylakoids), and enhanced rate of CO(2) fixation following exposure to heat stress (18 h at 45 degrees C) [Fu et al. in Plant Mol Biol 68:277-288, 2008]. In the current study, we investigated the segregation pattern and expression of the transgene Zmeftu1 and determined the grain yield of transgenic plants after exposure to a brief heat stress (18 h at 45 degrees C). We also assessed thermal aggregation of soluble leaf proteins in transgenic plants, testing the hypothesis that increased levels of EF-Tu will lead to a non-specific protection of leaf proteins against thermal aggregation. The transgenic wheat displayed a single-gene pattern of segregation of Zmeftu1. Zmeftu1 was expressed, and the transgenic plants synthesized and accumulated three anti-EF-Tu cross-reacting polypeptides of similar molecular mass but different pI, suggesting the possibility of posttranslational modification of this protein. The transgenic plants also showed better grain yield after exposure to heat stress compared with their non-transgenic counterparts. Soluble leaf proteins of various molecular masses displayed lower thermal aggregation in transgenic than in non-transgenic wheat. The results suggest that overexpression of chloroplast EF-Tu can be beneficial to wheat tolerance to heat stress. Moreover, the results also support the hypothesis that EF-Tu contributes to heat tolerance by acting as a molecular chaperone and protecting heat-labile proteins from thermal aggregation in a non-specific manner. PMID- 20306119 TI - Novel topical microbicides through combinatorial strategies. AB - PURPOSE: Developing microbicides for topical epithelial applications is extremely challenging, as evidenced by the scarcity of approved products even after decades of research. Chemical enhancers, including surfactants, are known to be effective antimicrobial agents but are typically toxic towards epithelial cells. Here, we report on the discovery of unique surfactant formulations with improved safety and efficacy profile for epithelial applications, via a combination of high throughput screening techniques. METHODS: Over three-hundred formulations derived from nine surfactants were screened for antibacterial properties against E. coli in vitro. A subset of these formulations showed high antibacterial activity and was screened for cytotoxicity in vitro. Formulations showing high antibacterial activity and reduced cytotoxicity compared to their individual components were tested for efficacy against B. thailendensis, a model for melioidosis-causing B. pseudomallei. RESULTS: Lead formulations showed lower toxicity towards epidermal keratinocytes, with LC(50) values up to 3.5-fold higher than their component surfactants, while maintaining antibacterial efficacy against B. thailendensis. CONCLUSIONS: Our results demonstrate that such a combinatorial screening approach can be used for designing safe and potent microbicides for epithelial applications. PMID- 20306120 TI - Apigenin: a promising molecule for cancer prevention. AB - Apigenin, a naturally occurring plant flavone, abundantly present in common fruits and vegetables, is recognized as a bioactive flavonoid shown to possess anti-inflammatory, antioxidant and anticancer properties. Epidemiologic studies suggest that a diet rich in flavones is related to a decreased risk of certain cancers, particularly cancers of the breast, digestive tract, skin, prostate and certain hematological malignancies. It has been suggested that apigenin may be protective in other diseases that are affected by oxidative process, such as cardiovascular and neurological disorders, although more research needs to be conducted in this regard. Human clinical trials examining the effect of supplementation of apigenin on disease prevention have not been conducted, although there is considerable potential for apigenin to be developed as a cancer chemopreventive agent. PMID- 20306122 TI - Stigmatization and male identity: Norwegian males' experience after identification as BRCA1/2 mutation carriers. AB - In families with hereditary breast and ovarian cancer, there is limited knowledge about the reactions of BRCA1/2 mutation positive males. In the present qualitative study, fifteen BRCA1/2 mutation positive men in Norway participated in two successive, in-depth interviews. Seven female partners participated in the second interview. The men reported strong emotional reactions to their positive test results, and they expressed a desire to keep the genetic information private. They considered discussing their test results or health related information with other males as difficult, and they perceived females as their sources of social and emotional support. Interestingly, the second interview revealed important information not communicated during the first interview. The findings of this study contribute to the discussion of whether men who test positive for a BRCA1/2 mutation should receive tailored genetic counseling sessions. Health care providers should be aware of psychological vulnerability in these men, likely stemming from fewer emotional supports in their social networks. PMID- 20306121 TI - Regulation of microRNAs by natural agents: an emerging field in chemoprevention and chemotherapy research. AB - In recent years, microRNAs have received greater attention in cancer research. These small, non-coding RNAs could inhibit target gene expression by binding to the 3' untranslated region of target mRNA, resulting in either mRNA degradation or inhibition of translation. miRNAs play important roles in many normal biological processes; however, studies have also shown that aberrant miRNA expression is correlated with the development and progression of cancers. The miRNAs could have oncogenic or tumor suppressor activities. Moreover, some miRNAs could regulate formation of cancer stem cells and epithelial-mesenchymal transition phenotype of cancer cells which are typically drug resistant. Furthermore, miRNAs could be used as biomarkers for diagnosis and prognosis, and thus miRNAs are becoming emerging targets for cancer therapy. Recent studies have shown that natural agents including curcumin, isoflavone, indole-3-carbinol, 3,3' diindolylmethane, (-)-epigallocatechin-3-gallate, resveratrol, etc. could alter miRNA expression profiles, leading to the inhibition of cancer cell growth, induction of apoptosis, reversal of epithelial-mesenchymal transition, or enhancement of efficacy of conventional cancer therapeutics. These emerging results clearly suggest that specific targeting of miRNAs by natural agents could open newer avenues for complete eradication of tumors by killing the drug resistant cells to improve survival outcome in patients diagnosed with malignancies. PMID- 20306123 TI - The obligate alkaliphile Bacillus clarkii K24-1U retains extruded protons at the beginning of respiration. AB - Alkaliphiles grow under alkaline conditions that might be disadvantageous for the transmembrane pH gradient (Delta pH, outside acidic). In this study, the behaviors of extruded protons by the respiration of obligate alkaliphilic Bacillus clarkii K24-1U were investigated by comparison with those of neutralophilic Bacillus subtilis IAM 1026. Although whole-cell suspensions of both Bacillus species consumed oxygen immediately after the addition of air, there were lag times before the suspensions were acidified. Under alkaline conditions, the lag time for B. clarkii significantly increased, whereas that for B. subtilis decreased. In the presence of valinomycin or ETH-157, which disrupts the membrane electrical potential (Delta psi), the cell suspensions of both Bacillus species acidified immediately after the addition of air. Artificial electroneutral antiporters (nigericin and monensin) that eliminate the Delta pH exhibited no significant effect on the lag times of the two Bacillus species except that monensin increased the lag times of B. clarkii. The inhibition of ATPase and the Na(+) channel also exhibited little effects on the lag times. The increased lag time for B. clarkii may represent the Delta psi-dependent proton retention on the outer surface of the cytoplasmic membrane to generate a sufficient Delta pH under alkaline conditions. PMID- 20306124 TI - Genetic analysis of the VP1 region of enterovirus 71 reveals the emergence of genotype A in central China in 2008. AB - Enterovirus 71 (EV71) strains from children were characterized by full-length VP1 nucleotide sequencing. Out of 22 clinical specimens, five isolates identified as EV71 were recovered by virus isolation. The VP1 sequences of the five isolates had more than 97.4% sequence identity with prototype virus BrCr, clustering in the genotype A lineage. This represents the first record of genotype A EV71 in China since the BrCr prototype strain was discovered in the USA in 1969. PMID- 20306125 TI - Characterization of begomovirus components from a weed suggests that begomoviruses may associate with multiple distinct DNA satellites. AB - A begomovirus disease complex associated with Sonchus arvensis, a common weed in Pakistan was studied using cloning, nucleic acid sequencing and phylogenetic analysis. The complex associated with this weed consists of a monopartite begomovirus and several distinct betasatellites and alphasatellites. The monopartite begomovirus associated with yellow vein disease of Sonchus arvensis showed 95-99% nucleotide sequence identity with Alternanthera yellow vein virus (AlYVV) reported from China, Vietnam and India. Two betasatellites were isolated from S. arvensis: one sharing between 91.4 and 95.3% nucleotide sequence identity with isolates of Ageratum yellow leaf curl betasatellite (AYLCB), and the other sharing between 78.2 and 99.9% identity with isolates of Cotton leaf curl Multan betasatellite (CLCuMB). Two alphasatellites were identified: one was homologous to Potato leaf curl alphasatellite (PotLCuA), while the other was closely related to Hibiscus leaf curl alphasatellite (HLCuA). Thus, AlYVV in S. arvensis is associated with satellites shown previously to be associated with other begomoviruses in Pakistan. Our results suggest that monopartite begomoviruses may associate with distinct satellites that are prevalent in the region. PMID- 20306126 TI - Genome organization of major tandem repeats in the hard tick, Ixodes scapularis. AB - In spite of the global medical and veterinary importance of Ixodid ticks, relatively little is known about their genome organization. To address this, we developed the first fluorescence in situ hybridization (FISH)-based chromosome markers in the Lyme disease vector, Ixodes scapularis. Shotgun genomic DNA (gDNA) sequences were used to identify three major tandem repeat families which were localized to specific heterochromatic regions of I. scapularis chromosomes prepared from the mitotic cell line ISE18. Together, these repeats were estimated to contribute approximately 159 Mb (8%) of the 2.1 Gb (haploid) I. scapularis genome. The relative arrangement of each tandem repeat family and the nucleolar organizing regions was determined by rehybridization to individual chromosome spreads, which was useful to distinguish different chromosomes in the ISE18 karyotype. Long stretches (>20 kb) of tandem repeat-containing gDNA were resistant to digestion by the methylation-sensitive restriction enzyme HpaII and localized to the presumed peri-centromeric regions of the chromosomes. A telomeric probe based on the arthropod-conserved (TTAGG)(n) tandemly repetitive motif was localized to the termini of each I. scapularis chromosome. Localization of these markers produced the first link between DNA sequences and major structural features of I. scapularis chromosomes and thereby provided the framework for a FISH-based physical map. PMID- 20306128 TI - Among women who experience a recurrence after postmastectomy radiation therapy irradiation is not associated with more aggressive local recurrence or reduced survival. AB - Recent pre-clinical models suggest that radiation can promote tumor aggressiveness. We hypothesized that if this were occurring clinically, locoregional recurrences (LRRs) after postmastectomy radiation therapy (PMRT) would lead to lower survival than LRR after mastectomy alone. This study used two independent datasets to compare survival after LRR in women treated with versus without PMRT. Data from 229 LRR cases among 1,500 patients enrolled on prospective trials at the MD Anderson Cancer Center (MDA), and 66 LRR cases among 318 patients enrolled in the British Columbia Cancer Agency (BCCA) PMRT randomized trial were analyzed. In the MDA non-randomized dataset, 189/1031 had LRR after mastectomy alone and 40/469 had LRR after PMRT. In the randomized BC trial dataset, 52/158 had LRR after mastectomy alone and 14/160 had LRR after PMRT. In both datasets, survival was calculated from the time of LRR to death. Analysis of MDA data shows that in all LRR cases regardless of distant metastasis (DM), 5/10-year OS were 50/34% without PMRT and 27/19% after PMRT (P = 0.006). However, PMRT-treated patients had increased risk factors for DM (advanced T and N stages) and more PMRT-treated patients developed DM prior to LRR (63 vs. 34%, P = 0.005). Analyzing only patients will an isolated LRR (without previous or simultaneous, DMV), there was no OS difference between groups (P = 0.33). Analysis of BCCA data shows that distributions of T and N stages were similar in patients with LRR after mastectomy alone versus after PMRT. DM free survival after any LRR and after isolated LRR were similar in mastectomy alone versus PMRT treated patients (P = 0.75, P = 0.26, respectively). Overall survival after any LRR and after isolated LRR were also similar in the two groups (P = 0.93, P = 0.28, respectively). Patients who develop LRR after mastectomy alone have high rates of DM and poor OS but these rates are not affected by the use of PMRT at the time of primary treatment. These data do not support the hypothesis that irradiation promotes biologically aggressive local recurrences. PMID- 20306127 TI - Decreased expression of EZH2 is associated with upregulation of ER and favorable outcome to tamoxifen in advanced breast cancer. AB - The purpose of this study is to investigate EZH2 in a large series of breast cancer patients for its prognostic and predictive value, and to evaluate its functional role in treatment response in vitro. EZH2 levels were measured using quantitative Real-Time Polymerase Chain Reaction (qRT-PCR) in primary breast cancer specimens and related to clinicopathologic factors and disease outcome. EZH2 expression was downregulated with siRNAs in MCF7, to assess expression alterations of putative EZH2 downstream genes and to determine cell numbers after treatment with the anti-estrogen ICI 164384. In 688 lymph node-negative patients who did not receive adjuvant systemic therapy, EZH2 was not significantly correlated with metastasis-free survival (MFS). In 278 patients with advanced disease treated with first-line tamoxifen monotherapy, the tertile with highest EZH2 levels was associated with the lowest clinical benefit (OR = 0.48; P = 0.02) and with a shorter progression-free survival (PFS) in both univariate (HR = 1.80; P < 0.001) and multivariate analysis, including traditional factors (HR = 1.61; P = 0.004). In vitro, EZH2 silencing in MCF7 caused a 38% decrease in cell numbers (P < 0.001) whereas ICI 164384 treatment resulted in a 25% decrease (P < 0.001) compared to controls. Combining EZH2 silencing with ICI treatment reduced cell numbers with 67% (P < 0.001) compared to control conditions. EZH2 downregulation was associated with an almost two-fold upregulation of the estrogen receptor alpha (ER) (P = 0.001). In conclusion, EZH2 has no prognostic value in breast cancer. High levels of EZH2 are associated with poor outcome to tamoxifen therapy in advanced breast cancer. Downregulated EZH2 leads to upregulation of the ER and better response to anti-estrogens. PMID- 20306129 TI - Cognitive function after adjuvant treatment for early breast cancer: a population based longitudinal study. AB - The purpose of this study was to examine cognitive function in patients with early breast cancer before and after adjuvant chemotherapy or 6 months of tamoxifen. We performed a population-based study in the county of North Jutland, Denmark, including 120 women aged <60 years who received adjuvant chemotherapy with seven cycles of cyclophosphamide, epirubicin and fluoruracil or adjuvant tamoxifen for 6 months for early breast cancer from 2004 to 2006. They were compared with an aged-matched group of 208 women without previous cancer selected randomly from the same population. Data were collected before start of adjuvant treatment and after 6 months by neuropsychological tests and questionnaires to evaluate cognitive function, quality of life and psychological distress. Neuropsychological tests did not reveal any differences in cognitive function between breast cancer patients after chemotherapy and healthy controls. Patients rated their own cognitive functions as improved after 6 months, and patients, who did not receive adjuvant medical treatment, reached the same level as controls within 6 months. Patients receiving chemotherapy or tamoxifen were up to three times more likely than controls to rate themselves as impaired at 6 months. Our results do not support that adjuvant chemotherapy is associated with cognitive side effects in breast cancer patients. PMID- 20306130 TI - Genetic algorithm optimization in drug design QSAR: Bayesian-regularized genetic neural networks (BRGNN) and genetic algorithm-optimized support vectors machines (GA-SVM). AB - Many articles in "in silico" drug design implemented genetic algorithm (GA) for feature selection, model optimization, conformational search, or docking studies. Some of these articles described GA applications to quantitative structure activity relationships (QSAR) modeling in combination with regression and/or classification techniques. We reviewed the implementation of GA in drug design QSAR and specifically its performance in the optimization of robust mathematical models such as Bayesian-regularized artificial neural networks (BRANNs) and support vector machines (SVMs) on different drug design problems. Modeled data sets encompassed ADMET and solubility properties, cancer target inhibitors, acetylcholinesterase inhibitors, HIV-1 protease inhibitors, ion-channel and calcium entry blockers, and antiprotozoan compounds as well as protein classes, functional, and conformational stability data. The GA-optimized predictors were often more accurate and robust than previous published models on the same data sets and explained more than 65% of data variances in validation experiments. In addition, feature selection over large pools of molecular descriptors provided insights into the structural and atomic properties ruling ligand-target interactions. PMID- 20306131 TI - Terlipressin in hepatorenal syndrome: a systematic review and meta-analysis. AB - BACKGROUND: Hepatorenal syndrome (HRS) is a common complication in patients with cirrhosis or fulminant liver failure. We systematically reviewed the benefits and harms of using terlipressin, a novel vasoconstricting agent in patients with HRS. METHODS: We searched MEDLINE, SCOPUS, and conference proceedings for relevant trials of terlipressin. Results were summarized using the random-effects model. RESULTS: Eight trials (320 participants) were included. When compared with placebo, terlipressin-treated patients had higher HRS reversal (odds ratio [OR] 7.47, 95% confidence interval [CI] 3.17-17.59), mean arterial pressure (weighted mean difference [WMD] 11.26 mmHg, 95% CI 1.52-21), and urine output. There was a significant increase in ischemic adverse events with terlipressin when compared to placebo. There was mild-to-moderate heterogeneity in these analyses. There was no significant difference between terlipressin and noradrenaline in HRS reversal (OR 1.23, 95% CI, 0.43-3.54), mean arterial pressure, and urine output. Side effect profile did not differ between terlipressin and noradrenaline. CONCLUSION: Terlipressin improves HRS reversal and other surrogate outcome measures compared with placebo, but no significant differences for these outcomes were noted when comparing terlipressin and noradrenaline. Terlipressin is a potential therapeutic option for HRS, but larger trials comparing terlipressin to other widely used vasoconstrictors are warranted. PMID- 20306133 TI - Predictive power of serum pepsinogen tests for the development of gastric cancer in comparison to the histologic risk index. AB - BACKGROUND AND AIM: The selection of a high-risk group of gastric cancer is important. This study was performed to compare the efficacy of non-invasive gastric cancer screening through the measurement of pepsinogen (PG) I/II ratio and endoscopic screening using histologic criteria (Meining's risk index for gastric cancer) in Korean patients. METHODS: Included in the study were 460 gastric cancer patients and 460 control cases who underwent upper endoscopy between June 2003 and July 2008 at Seoul National University Bundang Hospital. Serum PG I/II ratio and histologic characteristics were evaluated for each participant. Multivariate logistic regression was performed to compare the predictive power for gastric cancer of both the PG II/I ratio (the inverse form of PG I/II ratio) and the histologic gastric cancer risk index. RESULTS: A higher PG II/I ratio was significantly associated with a higher risk for gastric cancer (odds ratio of highest quartile for cancer vs. lowest quartile, 3.51; 95% confidence interval, 2.29-5.36) in the multivariate logistic model. The validity (in terms of calibration and discrimination) of the PG-including multivariate logistic model was comparable to the histologic gastric cancer risk index model. The results were similar regardless of the staging of the cancer, Lauren's histologic classification, and the location of the cancer. CONCLUSIONS: These results suggest that non-invasive measurement of serum PG I/II ratio is as effective as Meining's histologic gastric cancer risk index in predicting gastric cancer occurrence. PMID- 20306132 TI - Practice-driven evaluation of a multi-layered psychosocial care package for children in areas of armed conflict. AB - Psychosocial and mental health service delivery frameworks for children in low income countries are scarce. This paper presents a practice-driven evaluation of a multi-layered community-based care package in Burundi, Indonesia, Sri Lanka and Sudan, through a set of indicators; (a) perceived treatment gains; (b) treatment satisfaction; (c) therapist burden; (d) access to care; (e) care package costs. Across four settings (n = 29,292 children), beneficiaries reported high levels of client satisfaction and moderate post-treatment problem reductions. Service providers reported significant levels of distress related to service delivery. Cost analyses demonstrated mean cost per service user to vary from 3.46 to 17.32 depending on country and specification of costs. The results suggest a multi-layered psychosocial care package appears feasible and satisfactory in reaching out to substantial populations of distressed children through different levels of care. Future replication should address therapist burden, cost reductions to increase sustainability and increase evidence for treatment efficacy. PMID- 20306134 TI - The lamellar spacing in self-assembling bacteriochlorophyll aggregates is proportional to the length of the esterifying alcohol. AB - Chlorosomes from green photosynthetic bacteria are large photosynthetic antennae containing self-assembling aggregates of bacteriochlorophyll c, d, or e. The pigments within chlorosomes are organized in curved lamellar structures. Aggregates with similar optical properties can be prepared in vitro, both in polar as well as non-polar solvents. In order to gain insight into their structure we examined hexane-induced aggregates of purified bacteriochlorophyll c by X-ray scattering. The bacteriochlorophyll c aggregates exhibit scattering features that are virtually identical to those of native chlorosomes demonstrating that the self-assembly of these pigments is fully encoded in their chemical structure. Thus, the hexane-induced aggregates constitute an excellent model to study the effects of chemical structure on assembly. Using bacteriochlorophyllides transesterified with different alcohols we have established a linear relationship between the esterifying alcohol length and the lamellar spacing. The results provide a structural basis for lamellar spacing variability observed for native chlorosomes from different species. A plausible physiological role of this variability is discussed. The X-ray scattering also confirmed the assignments of peaks, which arise from the crystalline baseplate in the native chlorosomes. PMID- 20306135 TI - Quantitative effects of coil packing density on cerebral aneurysm fluid dynamics: an in vitro steady flow study. AB - Over the past 15 years, coil embolization has emerged as an effective treatment option for cerebral aneurysms that is far less invasive than the long-standing convention of surgical clipping. However, aneurysm recurrence after coil embolization is not uncommon: recurrence rates as high as 50% have been reported in the literature. One factor that may contribute to recurrence after coiling is residual flow into the aneurysmal sac. At present, there is limited quantitative knowledge of the relationship between coil packing density and aneurysmal inflow. We present an in vitro fluid dynamic study of basilar tip aneurysm models that elucidates this relationship. At physiologically normal flow rates, we found that a packing density of 28.4% decreased aneurysmal inflow by 31.6% in a wide-neck model, and that a packing density of 36.5% decreased aneurysmal inflow by 49.6% in a narrow-neck model. Results also indicated that coiling reduced aneurysmal inflow more significantly at lower parent vessel flow rates, and that coiling reduced neck-plane velocity magnitudes more significantly for narrow-neck aneurysms. Our study provides novel quantitative information that could ultimately contribute to improved outcomes for patients with cerebral aneurysms by enabling more effective coil embolization. PMID- 20306136 TI - Limitation of finite element analysis of poroelastic behavior of biological tissues undergoing rapid loading. AB - The finite element method is used in biomechanics to provide numerical solutions to simulations of structures having complex geometry and spatially differing material properties. Time-varying load deformation behaviors can result from solid viscoelasticity as well as viscous fluid flow through porous materials. Finite element poroelastic analysis of rapidly loaded slow-draining materials may be ill-conditioned, but this problem is not widely known in the biomechanics field. It appears as instabilities in the calculation of interstitial fluid pressures, especially near boundaries and between different materials. Accurate solutions can require impractical compromises between mesh size and time steps. This article investigates the constraints imposed by this problem on tissues representative of the intervertebral disc, subjected to moderate physiological rates of deformation. Two test cylindrical structures were found to require over 10(4) linear displacement-constant pressure elements to avoid serious oscillations in calculated fluid pressure. Fewer Taylor-Hood (quadratic displacement-linear pressure elements) were required, but with complementary increases in computational costs. The Vermeer-Verruijt criterion for 1D mesh size provided guidelines for 3D mesh sizes for given time steps. Pressure instabilities may impose limitations on the use of the finite element method for simulating fluid transport behaviors of biological soft tissues at moderately rapid physiological loading rates. PMID- 20306137 TI - Community organizing network for environmental health: using a community health development approach to increase community capacity around reduction of environmental triggers. AB - The Community Organizing Network for Environmental Health (CONEH), a project of Community Action Against Asthma, used a community health development approach to improve children's asthma-related health through increasing the community's capacity to reduce physical and social environmental triggers for asthma. Three community organizers were hired to work with community groups and residents in neighborhoods in Detroit on the priority areas of air quality, housing, and citizen involvement in the environmental project and policy decision-making. As part of the evaluation of the CONEH project, 20 one-on-one semi-structured, in depth interviews were conducted between August and November 2005 involving steering committee members, staff members, and key community organization staff and/or community members. Using data from the evaluation of the CONEH project, this article identifies the dimensions of community capacity that were enhanced as part of a CBPR community health development approach to reducing physical and social environmental triggers associated with childhood asthma and the factors that facilitated or inhibited the enhancement of community capacity. PMID- 20306138 TI - An assessment of the impacts of timber plantations on water quality and biodiversity values of Marbellup Brook, Western Australia. AB - Despite the fact that the establishment and maintenance of blue gum plantations can potentially result in the removal of riparian vegetation, the presence of increased levels of sediments, pesticides, and nutrients, and consequently, the loss of in-stream biodiversity, few studies exist that have looked at the impacts of timber plantations on in-stream biota. The goals of this study were thus to determine water quality, riparian condition, and in-stream biodiversity values of local streams draining blue gum plantations in the Marbellup Brook catchment in Western Australia and to compare these values with those of streams associated with other land uses. Selected water quality and habitat variables and in-stream macroinvertebrate biodiversity were measured in 2006 and 2007 at 28 sites falling into five broad categories based on the predominant land use within 200 m of each study reach. Overall, the results indicated that "blue gum plantation" sites often had better water quality, riparian condition, and biodiversity values than "pasture unfenced," and sometimes "pasture fenced" sites, but water quality and biodiversity values at these sites were not as good as those associated with "remnant" native vegetation sites. The location of the blue gum plantation sites along the disturbance gradient investigated was attributed to both present management and past land uses in the subcatchments investigated. As this study was conducted at a time when blue gum plantations were in an on-growing phase, it was recommended that future research on the impact of blue gum plantations on waterways in southwestern Australia should include an investigation of the impacts of timber clear-cutting and extraction. Longer-term cumulative and downstream effects of blue gum plantations on local waterways also need to be investigated. PMID- 20306139 TI - Concentrations, distributions, and sources of polychlorinated biphenyls and polycyclic aromatic hydrocarbons in bed sediments of the water reservoirs in Slovakia. AB - Dredging water reservoirs is necessary to maintain accumulation capacity and to prevent floodings. As a first step, the quality of the bed sediments in water reservoirs must be determined before dredging operations. In this study, sediment samples from 34 stations of three selected water reservoirs (Zemplinska Sirava, Velke Kozmalovce, and Ruzin) were collected to investigate concentrations, distributions, and hazards of polychlorinated biphenyls (PCBs) and polycyclic aromatic hydrocarbons (PAHs) and to predict their possible sources. Total PCB concentrations were in the range of 20.4 to 2,325 ng/g. The maximum concentrations of PCBs were found in sediments from Zemplinska Sirava, which is in the vicinity of a former manufacturer of PCBs. The composition of PCBs was characterized by tri- and hexa-CB congeners, indicating the influence of contamination from the use of specific Delor mixtures, formerly produced and massively used on the territory of Slovakia. The data showed that the highest total PAH concentrations were associated with the sediments from the Velke Kozmalovce, ranging from 7,910 to 29,538 ng/g. On the other hand, the lowest total PAH concentrations (84-631 ng/g of dry weight) were found in the sediments of Zemplinska Sirava, an important recreational area in eastern Slovakia. The distribution of individual PAHs was similar among the three water reservoirs, and this, together with principal component analysis and diagnostic PAH ratios, suggests mainly pyrolytic contamination of the sediments. However, petrogenic inputs appear to be important in the Zemplinska Sirava sediments. PMID- 20306140 TI - An approach to partition the anthropogenic and natural components of heavy metal accumulations in roadside agricultural soil. AB - This paper describes a new approach that allows us to partition the anthropogenic and natural contributions to heavy metal accumulations in roadside agricultural soils. This approach, combining trend analysis and multivariate statistical analysis, partitions total heavy metals into three components: anthropogenic, natural, and unexplained residual. The approach was applied in a case study in Yixing City, China, to determine the spatial distributions of heavy metal accumulations. The results show that anthropogenic components of Pb, Cu, Zn, and Cd account for 52.4%, 23.04%, 5.09%, and 10.9% of total content, respectively. Spatial distributions of anthropogenic components are characterized by decreasing accumulation with increasing distance from the road. Ranges of influence of traffic for Pb, Cu, and Cd are beyond 300 m, whereas the range of Zn is less than 200 m. The spatial distributions of the four elements' natural components show relatively similar distribution patterns. Assessments of variable partition methods show that the predicted values of Pb, Cu, Zn, and Cd are consistent with their measured values. The anthropogenic components extracted from total contents of heavy metal will be useful for modeling heavy metal accumulations produced by human activities. PMID- 20306141 TI - Investigation and assessment of volatile organic compounds in water sources in China. AB - 456 water samples collected from 152 water sources in 2006 were analyzed for 21 volatile organic compounds (VOCs). Concentrations of 21 VOCs ranged from below method detection limits of the laboratory to 7.65 MUg/L (toluene), but seldom exceeded the concentration limits set in the National Drinking Water Quality Standards (GB5749-2006) or the National Environmental Quality Standards for Surface Water (GB3838-2002) of China. Of the 21 individual VOCs analyzed, 11 VOCs were detected in at least one sample at or above 1.0 MUg/L; 6.6% of the water samples had a detection of at least one VOC at or above 1.0 MUg/L, and 2.6% had a detection of at least two VOCs at or above 1.0 MUg/L. Based on the statistical data of detection frequencies above the method detection limits, 75% of the samples detected at least one VOC, and 65% of the samples detected at least two VOCs. Chloroform, toluene, and 1,2-dichloroethene were the three most frequently detected VOCs, with detection frequencies of 76.97%, 68.42%, and 44.08%, respectively. Volatile halogenated hydrocarbons and gasoline components were the two most frequently detected VOC groups. PMID- 20306142 TI - Structuring expert input for a knowledge-based approach to watershed condition assessment for the Northwest Forest Plan, USA. AB - Assessments of watershed condition for aquatic and riparian species often have to rely on expert opinion because of the complexity of establishing statistical relationships among the many factors involved. Such expert-based assessments can be difficult to document and apply consistently over time and space. We describe and reflect on the process of developing a computer-based decision support application from expert judgments for assessing aquatic and riparian conditions over the 100,000 km2 managed by the US federal government under the Northwest Forest Plan. The decision support system helped structure and document the assessment process and provided consistency and transparency to the evaluation methodology. However, many decisions and trade-offs were required in the expert engagement and model-building processes. Knowledge elicitation in an interactive group had a number of benefits over nominal group or Delphi processes, but efficient knowledge capture required considerable planning and expertise in the subject matter and modeling process. Communicating model results for validation was problematic and only effectively accomplished via in-person workshops. The choice to use different expert groups for each biophysical province provided more opportunities for participation and promoted greater ownership in the assessment, but it also led to increased variation among the resulting model structures. We propose three possible approaches for better managing the consistency of assessment models when multiple expert groups are involved. PMID- 20306143 TI - Controlled microscale diffusion gradients in quiescent extracellular fluid. AB - Microchannels offer a means of establishing concentration gradients of soluble factors over micron length scales representative of those in tissues. Here, we report the development of a microfluidic channel system wherein a hydrogel has been patterned to generate temporally and spatially stable concentration gradients of multiple solutes in quiescent extracellular fluid. The fluorophore Alexa Fluor 488 and a fluorescent glucose analog are used as probes to illustrate the generation of stable, reproducible, and linear probe concentration gradients. A method is described for estimating the diffusivity and hydrogel permeability of a solute from in situ imaging data. Concentration gradients are also generated in the presence of a mouse insulinoma cell line to demonstrate the compatibility of the system with living cells. The net transport and metabolism rate of the glucose analog is found to be heterogeneous and independent of the applied extracellular gradient. This system may be suitable for the study of cell response to various extracellular gradients of soluble factors. PMID- 20306144 TI - Genotypic characterization of environmental isolates of Cryptococcus gattii from Puerto Rico. AB - Cryptococcus neoformans and Cryptococcus gattii are found in distinct environments with some overlap around different parts of the world. However, no systematic surveys of these two pathogens have been reported from Puerto Rico, a tropical island uniquely situated between mainland USA and countries in South America. We carried out an exhaustive environmental survey in southwestern Puerto Rico for pathogenic Cryptococcus species. Twenty-two presumptive isolates of C. gattii from cacti and tree detritus were characterized in detail by physiological and molecular methods and seventeen strains were confirmed as C. gattii. Cryptococcus gattii isolates were haploid and majority of them were MATa [corrected] strains. Sixteen out of seventeen C. gattii isolates belonged to VGII/AFLP6 genotype while one isolate was a VGIV/AFLP7 genotype. The results are significant as Puerto Rico strains are distinct from VGIII/AFLP5 strains reported from Southern California, but similar to C. gattii VGII/AFLP6 molecular type implicated in recent outbreaks of cryptococcosis in Pacific Northwest and British Columbia, Canada, but different in its M13 fingerprinting, and a common genotype in South America. PMID- 20306145 TI - Crystal structure of the three FK506 binding protein domains of wheat FKBP73: evidence for a unique wFK73_2 domain. AB - Here we describe the crystal structure of the N-terminal domain of the FK506 binding protein (FKBP) from wheat (wFKBP73), which is the first structure presenting three FK domains (wFK73_1, wFK73_2 and wFK73_3). The crystal model includes wFK73_2 and wFK73_3 domains and only part of the wFK73_1 domain. The wFK73_1 domain is responsible for binding FK506 and for peptidyl prolyl cis/trans isomerase (PPIase) activity, while the wFK73_2 and wFK73_3 domains lack these activities. A structure-based sequence comparison demonstrated that the absence of a large enough hydrophobic pocket important for PPIase activity, and of the conserved residues necessary for drug binding in the wFK73_2 and wFK73_3 domains explains the lack of these activities in these domains. Sequence and structural comparison between the three wFKBP73 domains suggest that the wFK73_2 domain is the most divergent. A structural comparison of the FK domains of wFKBP73 with other FKBPs containing more than one FK domain, revealed that while the overall architecture of each of the three FK domains displays a typical FKBP fold, their relative arrangement in space is unique and may have important functional implications. We suggest that the existence of FKBPs with three FK domains offers additional interactive options for these plant proteins enlarging the overall regulatory functions of these proteins. PMID- 20306146 TI - Protective effects of Flos lonicera extract on acute liver injury by dimethylnitrosamine-induced in rats. AB - The aim of this study is to investigate effects of Flos lonicera extract (FLE) on acute liver injury model rats which induced by 35 mg/kg dimethylnitrosamine (DMN). Model rats were divided into hepatic injury control group (administrated with water), FLE group (administrated with FLE) and silymarin group (administrated with silymarin which is hepatotherapeutic drug) as positive control. They were examined including ALT, AST, ALP, gamma-GT, ALB and TP levels in serum, and MDA, GPx levels in liver tissue. In addition, pathologic changes, particularly fibrosis, were examined by Azan staining. The results revealed that the ALT, AST, ALP, gamma-GT, MDA GPx and liver fibrosis degree in the LJE group were lower than the silymarin group and control group, ALB and TP were higher than the silymarin group and control group. These results suggested that LJE may help in inhibiting of acute liver injury greater than silymarin. PMID- 20306147 TI - Product-form stationary distributions for deficiency zero chemical reaction networks. AB - We consider stochastically modeled chemical reaction systems with mass-action kinetics and prove that a product-form stationary distribution exists for each closed, irreducible subset of the state space if an analogous deterministically modeled system with mass-action kinetics admits a complex balanced equilibrium. Feinberg's deficiency zero theorem then implies that such a distribution exists so long as the corresponding chemical network is weakly reversible and has a deficiency of zero. The main parameter of the stationary distribution for the stochastically modeled system is a complex balanced equilibrium value for the corresponding deterministically modeled system. We also generalize our main result to some non-mass-action kinetics. PMID- 20306148 TI - Genetic ablation of CD36 does not alter mouse brain polyunsaturated fatty acid concentrations. AB - In the brain, polyunsaturated fatty acids (PUFA), especially arachidonic acid and docosahexaenoic acid (DHA), are required for regulating membrane fluidity, neuronal survival and signal transduction. Since the brain cannot synthesize n-6 and n-3 PUFA de novo, they must be supplied from the blood. However, the methods of PUFA entry into the brain are not agreed upon. This study tested the necessity of CD36, a candidate transporter of unesterified fatty acids, for maintaining brain PUFA concentrations by comparing brain PUFA concentrations in CD36(-/-) mice to their wild-type littermates. Because CD36(-/-) mice have been reported to have impaired learning ability, the PUFA concentrations in different brain regions (cortex, hippocampus, cerebellum and the remainder of brain) were investigated. At 9 weeks of age, the brain was separated into the four regions and fatty acid concentrations in total and phospholipid classes of these brain regions were analyzed using thin layer and gas chromatography. There were no statistical differences in arachidonic acid or DHA concentrations in the different brain regions between wild-type and CD36(-/-) mice, in total or phospholipid fractions. Concentrations of monounsaturated fatty acids were decreased in several phospholipid fractions in CD36(-/-) mice. These findings suggest that CD36 is not necessary for maintaining brain PUFA concentrations and that other mechanisms must exist. PMID- 20306149 TI - Dependence on emergency care among young adults in the United States. AB - BACKGROUND: Young adults have a high prevalence of many preventable diseases and frequently lack a usual source of ambulatory care, yet little is known about their use of the emergency department. OBJECTIVE: To characterize care provided to young adults in the emergency department. DESIGN, SETTING, AND PARTICIPANTS: Cross-sectional analysis of visits from young adults age 20 to 29 presenting to emergency departments (N = 17,048) and outpatient departments (N = 14,443) in the National Hospital Ambulatory Medical Care Survey and National Ambulatory Medical Care Survey. MAIN MEASURES: Visits to the emergency department compared to ambulatory offices. RESULTS: Emergency department care accounts for 21.6% of all health care visits from young adults, more than children/adolescents (12.6%; P < 0.001) or patients 30 years and over (8.3%; P < 0.001). Visits from young adults were considerably more likely to occur in the emergency department for both injury-related and non-injury-related reasons compared to children/adolescents (P < 0.001) or older adults (P < 0.001). Visits from black young adults were more likely than whites to occur in the emergency department (36.2% vs.19.2%; P < 0.001) rather than outpatient offices. The proportion of care delivered to black young adults in the emergency department increased between 1996 and 2006 (25.9% to 38.5%; P = 0.001 for trend). In 2006, nearly half (48.5%) of all health care provided to young black men was delivered through emergency departments. The urgency of young adult emergency visits was less than other age groups and few (4.7%) resulted in hospital admission. CONCLUSIONS: A considerable amount of care provided to young adults is delivered through emergency departments. Trends suggest that young adults are increasingly relying on emergency departments for health care, while being seen for less urgent indications. PMID- 20306150 TI - Factors associated with hepatitis B testing among Vietnamese Americans. AB - BACKGROUND: Chronic hepatitis B and hepatitis B-associated liver cancer is a major health disparity among Vietnamese Americans, who have a chronic hepatitis B prevalence rate of 7-14% and an incidence rate for liver cancer six times that of non-Latino whites. OBJECTIVE: Describe factors associated with hepatitis B testing among Vietnamese Americans. DESIGN: A population-based telephone survey conducted in 2007-2008. PARTICIPANTS: Vietnamese Americans age 18-64 and living in the Northern California and Washington, DC areas (N = 1,704). MAIN MEASURES: Variables included self-reports of sociodemographics, health care factors, and hepatitis B-related behaviors, knowledge, beliefs, and communication with others. The main outcome variable was self-reported receipt of hepatitis B testing. KEY RESULTS: The cooperation rate was 63.1% and the response rate was 27.4%. Only 62% of respondents reported having received a hepatitis B test and 26%, hepatitis B vaccination. Only 54% knew that hepatitis B could be transmitted by sexual intercourse. In multivariable analyses, factors negatively associated with testing included: age 30-49 years, US residence for >10 years, less Vietnamese fluency, lower income, and believing that hepatitis B can be deadly. Factors positively associated with testing included: Northern California residence, having had hepatitis B vaccination, having discussed hepatitis B with family/friends, and employer requested testing. Physician recommendation of hepatitis B testing (OR 4.46, 95% CI 3.36, 5.93) and respondent's request for hepatitis B testing (OR 8.37, 95% CI 5.95, 11.78) were strongly associated with test receipt. CONCLUSION: Self-reports of hepatitis B testing among Vietnamese Americans remain unacceptably low. Physician recommendation and patient request were the factors most strongly associated with test receipt. A comprehensive effort is needed to promote hepatitis B testing in this population, including culturally-targeted community outreach, increased access to testing, and physician education. PMID- 20306151 TI - Optimal technical management of stump closure following distal pancreatectomy: a retrospective review of 215 cases. AB - BACKGROUND: Pancreatic fistula (PF) is a major source of morbidity following distal pancreatectomy (DP). Our aim was to identify risk factors related to PF following DP and to determine the impact of technique of transection and stump closure. METHODS: We performed a retrospective review of 215 consecutive patients who underwent DP. Perioperative and postoperative data were collected and analyzed with attention to PF as defined by the International Study Group of Pancreatic Fistula. RESULTS: PF developed in 36 patients (16.7%); fistulas were classified as Grade A (44.4%), B (44.4%), or C (11.1%). The pancreas was transected with stapler (n = 139), cautery (n = 70), and scalpel (n = 3). PF developed in 19.8% of remnants which were stapled/oversewn and 27.7% that were stapled alone (p = 0.4). Of the 69 pancreatic remnants transected with cautery and oversewn, a fistula developed in 4.3% (p = 0.004 compared to stapled/oversewn; p = 0.006 compared to stapled/not sewn). The median length of postoperative hospital stay was significantly increased in patients who developed PF (10 vs. 6 days, p = 0.002) CONCLUSION: The method of transection and management of the pancreatic remnant plays a critical role in the formation of PF following DP. This series suggests that transection using electrocautery followed by oversewing of the pancreatic remnant has the lowest risk of PF. PMID- 20306152 TI - Transumbilical totally laparoscopic single-port Nissen fundoplication: a new method of liver retraction: the Istanbul technique. AB - INTRODUCTION: Mustafa Kemal Ataturk, founder of the Turkish Republic, had guarded many German scientists of a Jewish descent before the Second World War. Dr. Rudolf Nissen was one of the outstanding surgeons who had served in the Turkish university hospitals. He had created an antireflux procedure which is named after his own name while he was working in our clinic, the Cerrahpasa Hospital. From a laparoscopic approach, the Nissen fundoplication was the gold standard intervention for the surgical treatment of gastroesophageal reflux disease (GERD). Currently, video laparoscopic surgery is evolving quickly with the guidance of new technology. Single-port (SP) laparoscopic transumbilical surgery is one of the newest branches of advanced laparoscopy. DISCUSSION: Simple or complex manipulations may be performed with SP laparoscopic transumbilical surgery. The advantages, which are gained from conventional laparoscopy, can be invigorated by an SP laparoscopic approach. The retraction technique of the liver and the optical system were the most important factors, which made the Nissen fundoplication possible via single port. Here, we report that totally laparoscopic transumbilical SP Nissen fundoplication procedure was performed in three patients for sliding hiatal hernia with GERD. CONCLUSION: Totally laparoscopic transumbilical SP Nissen fundoplication is a safe and feasible technique for the surgical treatment of GERD. PMID- 20306153 TI - BioEnterics(r) intragastric balloon (BIB(r)). Single ambulatory center Spanish experience with 714 consecutive patients treated with one or two consecutive balloons. AB - BACKGROUND: The BioEnterics(r) Intragastric Balloon (BIB(r)) is a well established device for temporary treatment in morbidly obese patients. The aim of this study is the evaluation, in a population of 714 consecutive outpatient setting cases, BIB(r) results in terms of weight loss and comorbidity change. METHODS: BIB(r) was positioned in all cases after diagnostic endoscopy. The device was inflated under direct endoscopic vision with saline solution (600-700 ml) and methylene blue (10 ml). Intubation was carried out in patients with body mass index (BMI) > 40 kg/m(2) affected by sleep apnea or chronic obstructive pulmonary disease. After 6 months, balloon removal was carried out, and patients were discharged with drug therapy and 1,000 kcal diet. More than 100 patients underwent a second consecutive balloon positioning. One month from the removal of the first BIB, patients were given a second BIB. Patients were followed up weekly. Mortality, complications and their treatment, postplacement symptoms, comorbidities, BMI, percentage of excess BMI loss (%EBL), and percentage of excess weight loss (%EWL) were considered. Data are expressed as mean +/- standard deviation. RESULTS: From June 1, 2005, to May 31, 2007, 714 patients underwent BIB(r) placement (143 males/571 females; mean age, 38.4 +/- 16.1; mean BMI, 37.6 +/- 5.7 kg/m(2); mean EW, 56.3 +/- 27.1 kg). After 6 months, mean BMI was 31.1 +/- 7.2, mean %EWL was 41.6 +/- 21.8, mean BMI loss was 6.5 +/- 12.7, and mean %EBL was 44.5 +/- 22.6. Of 714 patients, 112 underwent a second BIB placement. At the time of the second balloon placement, mean BMI was 32.9 +/- 6.7 kg/m(2); range was 31-51. After the second balloon removal, mean BMI was 30.3 +/- 7.2. CONCLUSIONS: BIB(r) treatment is a safe and effective procedure for weight reduction, without mortality and with very low morbidity rates even in nonhospitalized patients. A second balloon can also be positioned without difficulties, achieving good results after 12 months of treatment. PMID- 20306154 TI - Psychological assessments of bariatric surgery patients. Development, reliability, and exploratory factor analysis of the PsyBari. AB - BACKGROUND: Bariatric surgery patients are required to receive psychological clearance before they are eligible for surgery. In spite of this, there are no standard assessment practices or tests designed specifically for these evaluations. OBJECTIVE: The objective of this study is to determine the reliability and construct validity of the PsyBari, a psychological test designed for bariatric surgery patients. METHODS: The PsyBari was administered to 752 patients. Internal consistency reliability and exploratory factor analyses were conducted. RESULTS: Items with high percentages of missing data, low communalities, and low item loadings were identified and deleted. Cronbach's alpha = 0.930 (0.940 for males and 0.927 for females). Six factors were obtained for each gender: for females, awareness of eating habits, early life problems due to weight, dysphoric feelings about weight, weight-related impairment, surgical anxiety, and guilty feelings related to eating; for males, physical impairment with depression, awareness of eating habits, early life problems due to weight, interpersonal support with anxiety about weight, anger, and guilty feelings about eating habits. CONCLUSIONS: Results indicate that there are unique psychometric parameters when constructing tests for bariatric surgery patients. The PsyBari has good overall reliability, although two of the 11 subscales have poor reliability. Factor analyses revealed six factors for each gender. Some factors were common for both genders, some were unique for each gender, and some consisted of mixed constructs. PMID- 20306155 TI - Use of mesophilic fungal amylases produced by solid-state fermentation in the cold hydrolysis of raw babassu cake starch. AB - Amylases constitute one of the most important groups of industrial enzymes, presenting several applications, such as in the food, textile, and ethanol manufacturing. In this work, a starchy residue from the Brazilian agroindustry, namely babassu cake, was used for the production of amylases by solid-state fermentation and for obtaining sugar hydrolysates, which can be used as building blocks for future bioconversions. Eight filamentous fungi from the genera Aspergillus and Penicillium were screened. Regarding amylase production, A. awamori strains showed well-balanced endoamylase and exoamylase activities, while A. wentii produced an amylolytic complex much richer in the endo-acting enzymes. Simultaneous liquefaction and saccharification using the crude enzyme extracts from the four most promising fungal strains was then investigated applying DOE techniques. The highest total reducing sugar content (24.70 g L(-1)) was obtained by the crude extract from A. awamori IOC-3914, corresponding to a hydrolysis yield of 52% of total starch in the cake, while A. awamori IOC-3915 produced the most appropriate extract in terms of glucose release (maximum of 5.52 g L(-1)). Multivariate analysis of the DOE studies indicated that these extracts showed their best performance at 50-57 degrees C under acid conditions (pH 3.6-4.5), but were also able to act satisfactorily under milder conditions (36 degrees C and pH 5.0), when TRS and glucose released were about 65% of the maximum values obtained. These data confirm the high potential of the enzyme extracts under study for cold hydrolysis of starch. PMID- 20306156 TI - The development of gastric cancer in a patient with polycythemia Vera, 3P deletion, and JAK2 V617F mutation. AB - 3p deletion which is frequently associated with solitary tumors and hematological malignancies is a chromosomal abnormality. Recently, Janus kinase-2 (JAK2) V617F mutation has an important role in the diagnosis of myeloproliferative disorders, especially in polycythemia vera (PV). We reported the development of gastric cancer in a 75-year-old patient with PV, 3p 12-14 deletion and JAK2 V617F mutation. PV was diagnosed according to the classification of World Health Organization. JAK2 V617F mutation with polymerase chain reaction and 3p12-14 deletion with cytogenetic examination of the bone marrow were detected. We investigated solitary tumors in the patient using computed tomographies of thorax, neck, ear, nose, and throat. However, they were normal. After 2 years, gastric cancer appeared in the patient. In conclusion, cytogenetic examination may be important in both the development and the diagnosis of hematological malignancies and solitary tumors. So the patients should be followed closely. PMID- 20306157 TI - The prevalence of the mutation in codon 249 of the P53 gene in patients with hepatocellular carcinoma (HCC) in Turkey. AB - Hepatocellular carcinoma (HCC) is one of the most common cancers in the worldwide. Aflotoxins, products of Aspergillus Flavus found in the high humidity environments induce HCC in humans by causing mutations in oncogenes such as codon 249 mutation of p53 in hepatocytes. In turkey, aflatoxins are found to be increased in some foods in certain areas, such as Istanbul which have high humidity. In present study we aimed to look for the prevalence of codon 249 mutation of p53 in patients with HCC, cirrhosis and chronic hepatitis B (CHB). METHODS: DNA was extracted from plasma and mutation was detected by PCR-RFLP method. RESULTS: the codon 249 mutation of p53 is found one out of 50 HCC (2%) patients. In conclusion, although codon 249 mutation of p53 gene has been found very rare but it exists showing the effect of aflatoxins in HCC patients in Turkey. PMID- 20306158 TI - Heterogeneity of mitochondrial membrane potential: a novel tool to isolate and identify cancer stem cells from a tumor mass? AB - It is believed that cancer stem cells (CSCs) are precursors for the formation, development, and recurrence of malignant tumors. However, it has proven difficult to isolate and enrich these rare, undifferentiated cells from heterogeneous tumor masses. With some existing reports and preliminary results in mind, we hypothesized that the mitochondrial membrane potential within a tumor mass was heterogeneous and could be used as a tool to isolate and enrich CSCs. PMID- 20306159 TI - Prolonged time to progression with fulvestrant for metastatic breast cancer. AB - Although the incidence of breast cancer has been declining in recent years, the disease is still one of the leading causes of cancer deaths in women. Recently, breast cancer has been treated with innovative approaches that use hormone sensitive therapies. This is because in at least one-third of breast cancers, estrogens mediated via the estrogen receptor pathway act as endocrine growth factors. Fulvestrant has been studied as both first- and second-line therapy for locally advanced and metastatic breast cancer, but few studies have shown its effect as third-line therapy alone. To observe the disease time to progression (TTP) obtained with fulvestrant when used on metastatic breast cancer as first-, second-, and also third-line therapy. We also aimed to correlate the TTP obtained with fulvestrant with hormone receptor, HER2 expression, and metastatic site. This was a cohort study that retrospectively examined medical records of 73 postmenopausal women with advanced breast cancer who were treated with fulvestrant (250 mg/month i.m. injection) and followed at the Department of Medical Oncology at Hospital do Cancer A. C. Camargo in Sao Paulo, Brazil from August 2003 to December 2006. The median TTP with fulvestrant was about 11 months. When used as the first-line therapy, TTP was about 13 months; when used as second-line, TTP was about 6 months; and when used as third-line, it was about 12 months. No statistically significant difference was observed regarding the therapy line. In patients with positive ER tumors, TTP was 11 months. No significant difference in TTP was observed in negative ER tumors (TTP = 10 months). In patients with positive PgR tumors, TTP was 13 months and for negative PgR, TTP was 6 months (P = 0.008). According to the HER2 status, the TTP was 5 months for HER2+ and 10 months for HER2-. Our findings indicate that fulvestrant is an effective alternative for treatment of metastatic breast cancer. PMID- 20306161 TI - FDG-PET/CT imaging in assessing mucin-producing non-small cell lung cancer with pathologic correlation. AB - OBJECTIVE: The objective of this study was to describe the PET/CT findings of mucin-producing non-small cell lung cancer (NSCLC) and how those findings are associated with pathology. METHODS: A review of all patients with FDG-PET/CT identified 11 patients with histopathologically confirmed mucin-producing NSCLC; 3 mucinous bronchioloalveolar carcinoma (mBAC), 5 mixed-type adenocarcinoma with prominent mucinous BAC pattern (ADENO + mBAC), and 3 mixed-type adenocarcinoma with mucin production (ADENO + MUCIN) in our institute. RESULTS: Among 11 patients, only 2 lesions (18%) evidenced positive PET results for standardized uptake value (SUV) of 3.5 (by ROC analysis) whereas all cases were detected correctly at CT. The mean SUV was 2.0 in the 9 lesions not detected and 2.5 in all cases. The mean SUV of pure mBAC was 1.93, that of mucin-producing adenocarcinoma was 2.69 without a significant difference (p = 0.279). No significant correlations between tumor size or stage and SUV were determined. CONCLUSIONS: PET/CT for SUV is limited in the detection of mucin-producing NSCLC. Therefore, the CT component of PET/CT may allow for significantly improved sensitivity and help to reduce delayed diagnose. The SUV in mBACs were lower than the other types of mucin-producing adenocarcinoma; however, we determined no significant difference to exist between the SUVs of two groups of lung cancer. PMID- 20306160 TI - Weight gain after adjuvant chemotherapy in patients with early breast cancer in Istanbul Turkey. AB - Weight gain is a well-known and unwanted complication of adjuvant chemotherapy in breast cancer. We observed that the female Turkish cancer patients frequently gain weight with adjuvant treatment of breast cancer and planned to examine the magnitude of this problem in early breast cancer patients treated at our hospital. A total of 176 early breast cancer patients who received their adjuvant systemic therapy in Marmara University Hospital between 2003 and 2007 are included in the study. We recorded their weight before and after chemotherapy and also a year after chemotherapy to find out whether the change with weight is transitory. We have also recorded demographic information, including the educational level, menopausal status, the type of chemotherapy or hormonal treatment administered stage of disease, marital status, occupation and the underlying diseases to analyze the relationship between change in weight and these parameters. Median age of patients was 53 and 72% of patients were postmenopausal. Educational level was equally distributed for primary education (27%), high school (40%), and university (33%). The majority of the patients (76%) was married, had two children (69%) and was housewife (60%). Family history of any cancer was high (32%). Most of the patients had stage II cancer (56%), received anthracyclines+/- taxane based chemotherapy (98%) and had no underlying disease (68%). The majority also did not smoke (73%) or drink alcohol (93%). A total of 67% and 72% patients gained weight upon completion and one year after completion of chemotherapy. Mean weight before the chemotherapy, upon completion of chemotherapy and one year after completion of chemotherapy were 68.9 kg, 70.6 kg (P = 0.000) and 71.9 kg (P = 0.000) respectively. Mean body mass index was 27.1 at baseline, 27.8 upon completion of chemotherapy (P = 0.000) and 28.3 one year after completion of chemotherapy (P = 0.000). Age, menopausal status, multiparity and presence of comorbid diseases had statistically significant impact on weight gain following adjuvant therapy in breast cancer patients (P = 0.000, P = 0.008, P = 0.015 and P = 0.017 respectively). This study shows that Turkish women with early breast cancer gain weight after adjuvant systemic therapy, in line with European and American counterparts. This increase in weight is maintained at least one year after adjuvant therapy. Given the adverse consequences of weight gain in terms of both breast cancer prognosis and general health, it is necessary to inform patients about this change and to develop strategies for weight maintenance during and after systemic therapy. PMID- 20306163 TI - 50 Years ago in CORR: epidemiology of fracture in aged persons: a preliminary investigation in fracture etiology Goran C. H. Bauer CORR 1960;17:219-225. PMID- 20306162 TI - Calcium phosphate cement with BMP-2-loaded gelatin microspheres enhances bone healing in osteoporosis: a pilot study. AB - BACKGROUND: The capacity for bone healing reportedly is limited in osteoporosis with a less than ideal environment for healing of bone grafts. We therefore developed a composite bone substitute with rhBMP-2 loaded gelatin microsphere (GM) and calcium phosphate cement (CPC) to use in osteoporosis. QUESTIONS/PURPOSES: We asked whether (1) controlled release of rhBMP-2 could be improved in this composite bone substitute and (2) increasing factors released from the bone substitute could accelerate osteoporotic bone healing. METHODS: We soaked rhBMP-2/GM/CPC and rhBMP-2/CPC composites in simulated body fluid for 28 days and then determined the amount of rhBMP-2 released. Both composites were implanted in bone defects of osteoporotic goats and left in place for 45 and 140 days; the specimens then were evaluated mechanically (pushout test) and morphologically (CT scanning, histology). RESULTS: The in vitro study showed the new composite released more rhBMP-2 compared with rhBMP-2/CPC. CT showed the defects healed more quickly with new grafts. The bone mineralization rate was greater in rhBMP-2/GM/CPC than in rhBMP-2/CPC after 45 days of implantation and the pushout test was stronger after 45 and 140 days of implantation. CONCLUSIONS: The new graft composite released more loaded factors and appeared to repair osteoporotic bone defects. CLINICAL RELEVANCE: These preliminary data suggest the new composite can be used as a bone substitute to accelerate healing of fractures and bone defects in osteoporosis. PMID- 20306164 TI - Percutaneous radiofrequency epiphysiodesis in a rabbit model: a pilot study. AB - BACKGROUND: Techniques for epiphysiodesis have evolved from open surgical techniques requiring direct observation of the physis to percutaneous techniques performed with fluoroscopy. QUESTIONS/PURPOSES: Our purposes were to (1) describe a new minimally invasive surgical technique used to achieve epiphysiodesis using radiofrequency ablation, (2) document the effect of radiofrequency ablation on tibia length at 2, 6, and 12 weeks after ablation in a skeletally immature rabbit model, and (3) assess the effects of radiofrequency ablation on the histologic appearance of the proximal tibia physis and proximal tibia articular cartilage. MATERIALS AND METHODS: We performed epiphysiodesis of the rabbit proximal tibia on 15 skeletally immature male New Zealand White rabbits using a 22-gauge radiofrequency probe. The probe was positioned percutaneously and heated to 90 degrees C for 4 minutes on the medial and lateral (1/2) of the physis. The opposite tibia was used as a control. Five animals were sacrificed at 2, 6, or 12 weeks postoperatively. Tibia length was compared using Faxitron(R) radiographs and electronic calipers. Histology of the growth plate was assessed with light microscopy. RESULTS: We observed differences in tibia length between 4.16 mm and 11.59 mm (average 7.86 mm) at 12 weeks. The proximal tibia physis closed radiographically and histologically in all animals by 12 weeks. Histologic analysis showed no evidence of articular cartilage injury. CONCLUSIONS: This technique was reproducible and resulted in bone fusion of the rabbit proximal tibial growth plate. The use of radiofrequency ablation as described in this report may be used as an alternative to other surgical epiphysiodesis techniques. CLINICAL RELEVANCE: This technique may be useful for epiphysiodesis of small tubular bones of the hands and feet in humans. PMID- 20306165 TI - Introduction to special series: The great debate--evaluating the health implications of positive psychology. AB - BACKGROUND: In recent years, investigators have focused increased attention on positive psychology constructs and their associations with health outcomes, such as morbidity, mortality, and adaptation to illness. The database regarding some of these concepts and models has grown appreciably, but work in this area has been subject to controversy. PURPOSE: This special series of papers offers contrasting perspectives regarding research on positive psychology and health. Both proponents and critics were invited to review recent developments concerning a number of positive constructs that have been evaluated in the oncology literature and in health research, more generally. METHODS: Papers are presented in the format of a debate. Significant advances are reviewed by one set of investigators, Drs, Lisa G. Aspinwall and Richard G. Tedeschi, while shortcomings and concerns are highlighted by another set of investigators, Drs. James C. Coyne and Howard Tennen. Each of these review papers is followed by a rebuttal by the opposing side. A commentary on the exchange is provided by Dr. Sherri Sheinfeld Gorin. RESULTS: These papers address a range of important considerations regarding conceptualization of constructs, methodological rigor, dissemination of findings, and implications for practice. CONCLUSION: The critiques and recommendations offered in these papers may help inform future efforts in this area, as the field continues to evolve. PMID- 20306166 TI - Minute myopericytoma of the neck: a case report with literature review and differential diagnosis. AB - Reports of cutaneous myopericytoma (MPC) are very rare. The author herein reports a case of minute MPC of the neck. A 56-year-old woman noticed a painful small tumor in the neck, and consulted to our hospital. Dermatologists's diagnosis is a hyperplastic lymph node. Excision of the tumor was performed. Grossly, the tumor was a sold white tumor measuring 3 * 3 * 3 mm. Microscopically, it consisted of many vascular channels and perivascular cell proliferation encased by a fibrous capsule. The vascular proliferation showed a hemangiopericytoma (HPC)-like pattern such as staghorn-like vessels. Fibrosis was not present. The HPC-like cells had vesicular nuclei and polygonal cytoplasm. No atypia is recognized. The HPC-like cells focally showed vague nodular proliferation around the vessels. Immunohistocheically, the tumor cells were negative for cytokeratin, and positive for vimentin. The vasculatures were positive for factor VIII-related antigen, CD34, and CD31. The HPC-like tumor cells were positive for alpha-smooth muscle actin and h-caldesmon, but negative for desmin, S100 protein, melanosome, bcl-2, CD99, and KIT. The Ki-67 labeling was 8% and p53 was negative. The pathologic diagnosis was MPC of the neck skin. The patient is now alive without recurrence 4 years after the excision. A review of the literature revealed 73 cases of MPC from 6 papers. MPC is male predominance, and the patients ages ranges from 13 to 87 years with the median of 47 years. The most common location was lower extremities followed in order by upper extremities, head and neck, and trunk. One MPC occurred within the vasculature, and 3 cases of MPC developed in the scar or trauma lesions. The prognosis after excision is good, but a very minority showed local recurrence. A differential diagnosis was also made. PMID- 20306167 TI - Functional importance of the astrocytic glycogen-shunt and glycolysis for maintenance of an intact intra/extracellular glutamate gradient. AB - It has been proposed that a considerable fraction of glucose metabolism proceeds via the glycogen-shunt consisting of conversion of glucose units to glycogen residues and subsequent production of glucose-1-phosphate to be metabolized in glycolysis after conversion to glucose-6-phosphate. The importance of this as well as the significance of ATP formed in glycolysis versus that formed by the concerted action of the tricarboxylic acid (TCA) cycle processes and oxidative phosphorylation for maintenance of glutamate transport capacity in astrocytes is discussed. It is argued that glycolytically derived energy in the form of ATP may be of particular functional importance in this context. PMID- 20306168 TI - Which xenobiotic(s) could be responsible for the radiologic findings below? Answer: any proconvulsant xenobiotic, in this case tramadol, bupropion, and nortriptyline. AB - BACKGROUND: The proconvulsive properties of tramadol, bupropion, and nortriptyline have been well documented. Spinal fractures secondary to drug induced seizures have been rarely reported. CASE REPORT: A 39-year-old female presented with a chief complaint of back pain. She went to bed feeling well in a separate room from her husband. During the previous night, he heard a noise and went into her room, finding her confused and twisted in an awkward position on her bed. Later she complained to him of severe back pain, prompting transport to a hospital. Shortly after arrival in the emergency department, staff witnessed a generalized convulsion. Following a one-hour post-ictal period, she complained of worsened back pain. Lab studies were normal, including a urine tox screen for drugs of abuse. No alcohol was implicated. ECG showed sinus rhythm, HR 113 beats/min, QRS 108 ms, QTc 389 ms. Brain magnetic resonance imaging (MRI) was normal. X-ray and an MRI of the thoracic spine confirmed four contiguous vertebral compression fractures, from T2 through T5. EEG showed diffuse changes consistent with a metabolic or toxicologic process. She denied taking any drugs other than prescribed doses of her medications, which included tramadol, bupropion, and nortriptyline. She had no previous history of seizures, head injury, or CVA. Bupropion and tramadol were discontinued, and seizures did not recur. CASE DISCUSSION: This patient's history, EEG findings, and brain imaging all point to a metabolic or toxic cause. It is likely that her three proconvulsant medications--even at therapeutic doses--synergistically lowered her seizure threshold or even precipitated her seizures. Retrospective studies and case reports portray these drugs as potentially offending agents. CONCLUSIONS: Sudden onset of back pain during sleep can be an important clue to a seizure complicated by vertebral compression fractures, even in the absence of trauma. Toxicology consultation in seizures of unclear etiology can help discern drugs that offend even in therapeutic doses. PMID- 20306169 TI - Severe neurotoxicity following ingestion of tetraethyl lead. AB - Organic lead compounds are potent neurotoxins which can result in death even from small exposures. Traditionally, these compounds are found in fuel stabilizers, anti-knock agents, and leaded gasoline. Cases of acute organic lead intoxication have not been reported for several decades. We report a case of a 13-year-old Iraqi male who unintentionally ingested a fuel stabilizer containing 80-90% tetraethyl lead, managed at our combat support hospital. The patient developed severe neurologic symptoms including agitation, hallucinations, weakness, and tremor. These symptoms were refractory to escalating doses of benzodiazepines and ultimately required endotracheal intubation and a propofol infusion. Adjunctive therapies included chelation, baclofen, and nutrition provided through a gastrostomy tube. The patient slowly recovered and was discharged in a wheelchair 20 days after ingestion, still requiring tube feeding. Follow-up at 62 days post ingestion revealed near-resolution of symptoms with residual slurred speech and slight limp. This case highlights the profound neurotoxic manifestations of acute organic lead compounds. PMID- 20306170 TI - Spatial and temporal variations of heavy metals in surface sediments in Bohai Bay, North China. AB - Characteristics of the spatial and temporal distributions of selected heavy metals (Cu, Zn, Cd, Pb and Hg) in Bohai Bay, north China was examined. Surface sediment samples from 15 sites were collected and analyzed for the selected metals with atomic absorption spectrometry (AAS) from the year of 1997-2007. Mean concentrations of metals in the 11-year period showed that Hg and Zn concentrations slightly fluctuated, while Cu, Cd and Pb concentrations in sediments varied with time. High levels of heavy metals occurred not only along the shoreline but also at some site in the inner part of the bay, suggesting the contamination sources of heavy metals from both terrestrial inputs and the atmospheric deposition. Compared with the environmental background values of selected heavy metals it indicated that anthropogenic activities influenced the sediment quality. The contamination factor C(fi), which is used to evaluate the pollution of the environment, showed that the contamination by selected heavy metals was moderate. Cd, Zn and Pb were the main polluting elements in this area. PMID- 20306171 TI - Dynamics of carbendazim residue in Panax notoginseng and soil. AB - To provide scientific information for GAP of P. notoginseng and guiding the farmers and enterprises of Chinese medicine, dynamics of carbendazim residue in the Chinese medicinal herb, P. notoginseng and cultivated soil was studied at Wenshan County in 2008. The half lives of carbendazim in P. notoginseng were 5.92 6.82 day (soil), 6.71-6.77 day (fresh leaf), 3.29-3.93 day (fresh root), and 31.50-36.67 day (powder of the dry root) separately. Carbendazim residues in P. notoginseng were more stable during storage stage than growing stage. PMID- 20306172 TI - Sensitivity comparison of laboratory-cultured and field-collected amphipod Corophium multisetosum in toxicity tests. AB - The feasibility of using lab-cultured amphipods Corophium multisetosum (Stock 1952) to evaluate the toxicity of contaminants present within marine sediments was studied. This was done by comparing the sensitivity of lab-cultured amphipods in a cadmium toxicity test and to toxic sediment samples, during a 10-days bioassay, with field collected individuals. Different responses were observed between field and cultured individuals. Cadmium test indicated high temporal variability in the LC(50) values of field amphipods (2.40-6.55 mg L(-1)). Sensitivity of cultured amphipods was within the seasonal range of the field individuals (5.81 mg L(-1), LC(50)). However, culture amphipods showed much lower sensitivity in toxic sediment samples. Our results indicate that sensitivity should be determined using a sediment matrix, if the assessment of toxicity is based upon bioassays performed with cultured burrower-amphipods. PMID- 20306173 TI - Monitoring of fluoride in groundwater resources of Iran. AB - Fluoride concentration in groundwater resources that used as the source of drinking water in urban areas of Iran was determined. All of the groundwater wells located in urban areas were monitored in 2008. Fluoride concentration of water samples was measured using SPADNS method. The nationwide mean fluoride concentration in the groundwater resources was found to be 0.47 +/- 0.28 (+/- standard deviation) mg/L. Only in Bushehr Province, the provincial mean fluoride level in the groundwater resources was higher than the WHO guideline value of 1.5 mg/L (1.86 +/- 0.86 mg/L). At nationwide level, the portion of extracted groundwater with fluoride concentration lower than the minimum permissible level of 0.5 mg/L, desirable fluoride range of 0.5-1.5 mg/L and elevated fluoride level was 69.2, 29.3 and 1.4%, respectively. In the areas with low fluoride content drinking water, it is recommended that fluoride is absorbed by use of high fluoride content foods and beverages. The recommendations for the circumstances with excessive fluoride content of drinking water are provision of drinking water from alternative sources and defluoridation of drinking water by point-of-use systems, respectively. PMID- 20306174 TI - Measurement of pelvic floor muscular strength with the Colpexin pull test: a comparative study. AB - INTRODUCTION AND HYPOTHESIS: The aim of this study is to compare the Colpexin pull test (CPT) with the Oxford muscle grading scale (OMGS) in assessing pelvic floor muscle strength. METHODS: In phase 1, 15 asymptomatic women underwent OMGS and CPT using three different spheres to select the ideal size. CPT values as well as patient/examiner comfort and ease of CPT performance were recorded. In phase 2, 30 women with stress urinary incontinence underwent CPT and OMGS by two examiners during two separate sessions. Statistical analysis was performed. RESULTS: In phase 1, the 36-mm sphere was selected based on resting (p < 0.001), contraction CPT (p < 0.001), patient ease (p = 0.018), patient comfort (p = 0.004), and examiner comfort (p < 0.001). In phase 2, there was good intra-rater and inter-rater agreement in maximum CPT. Both tests were positively correlated (r = 0.50, p < 0.001). CONCLUSION: CPT is an objective measure of pelvic floor strength and provides consistent, reproducible results. PMID- 20306176 TI - Quantitative coherence analysis with an X-ray Talbot-Lau interferometer. AB - Differential phase-contrast (DPC) X-ray imaging has been performed in the Talbot Lau configuration, in which the X-ray source was a combination of an absorption grating and a laboratory X-ray generator. We report here quantitative analysis of partial coherence effects on the X-ray Talbot-Lau interferometer. Based on the visibility of the self-image, the well-known geometry condition is reproduced. It is shown that effects of partial coherence are determined by the opening ratio of the source grating, and that the effects are independent of the Talbot order and the type of the phase grating, a condition quite different from those in a Talbot interferometer. A possible explanation is discussed from the point of view of the effective spatial coherence length. Taking into account the available X-ray flux and experimental fluctuations, we present the optimum opening ratio. Furthermore, we mention that our results can also be successfully used to discuss the properties of a multiline X-ray source. PMID- 20306175 TI - Varenicline's effects on acute smoking behavior and reward and their association with subsequent abstinence. AB - RATIONALE: Varenicline may aid smoking cessation by attenuating smoking behavior and reward. We compared the effects of varenicline versus placebo on smoking behavior and reward, assessed both prospectively and retrospectively, and related these effects to subsequent success in a brief simulated quit attempt with medication. MATERIALS AND METHODS: Smokers (n = 124) with high or low interest in quitting smoking participated in a double-blind crossover study of varenicline versus placebo effects on smoking behavior and reward. In each of two phases, subjects received a week of medication run-up with varenicline (0.5 mg, b.i.d.) or placebo while continuing to smoke, followed the next week by an attempt to quit while on medication. At the end of each run-up week, subjects completed retrospective measures of smoking reward (liking) and number of cigarettes over the prior 24 hrs, and they provided an expired air carbon monoxide (CO) measure. They then completed a prospective session in which they ad lib smoked and rated the rewarding effects of one of their preferred cigarettes while blind to brand. RESULTS: Varenicline decreased smoking reward significantly in the prospective assessment, but only marginally in the retrospective assessment. Varenicline did not alter smoking behavior prospectively, but did reduce CO and retrospective report of smoking amount. None of these effects of varenicline predicted subsequent days of abstinence due to varenicline. CONCLUSIONS: During medication run-up, varenicline decreases acute smoking reward and may attenuate smoking behavior, but these effects do not appear to directly predict varenicline's influence on smoking abstinence in a short-term test. PMID- 20306177 TI - A reusable liposome array and its application to assay of growth-hormone-related peptides. AB - We describe a reusable liposome array based on the formation of cleavable disulfide cross-links between liposomes and the surface of a glass slip. The N succinimidyl 3-(2-pyridyldithio)-propionate (SPDP)-modified liposomes encapsulating a pH-sensitive fluorescence dye were immobilized on a 3 mercaptopropyltrimethoxysilane (MTS)-modified glass slip through the formation of disulfide bonds. The regeneration of a used slip was performed by the lysis of immobilized liposomes with Triton X-100 and the cleavage of disulfide bonds by reduction with TCEP, followed by immobilization of SPDP-modified liposomes. The regeneration steps did not affect the fluorescence intensity of re-immobilized liposomes. The liposome array was applied to simultaneous quantification of growth hormone related peptides, i.e., GHRF and somatostatin, in a mixture. After optimizing the assay condition, the method allowed quantification of GHRF and somatostatin in concentration ranges from 0.5 x 10(-9) to 0.5 x 10(-7) g/mL with detection limits of 2 x 10(-10) and 3 x 10(-10) g/mL, respectively. PMID- 20306178 TI - Organometallic derivatizing agents in bioanalysis. AB - Over the last few decades, the development of several innovative hyphenated analytical techniques and their routine use in laboratories has led to new possibilities for the quantitative analysis of biomolecules. Today, the identification and quantification of biomolecules such as peptides and proteins are essential to answer important medical, pharmaceutical, and biological questions. To allow efficient detection and structure elucidation of biomolecules, several approaches including derivatization strategies were investigated and applied during recent years. This article summarizes the current approaches for labeling and presents the different types of organometallic derivatizing agents used as labels. Furthermore, their analytical potential with respect to quantification and structure elucidation for different applications in the field of bioanalysis is discussed. PMID- 20306179 TI - In vitro and intracellular sensing by using the photoluminescence of quantum dots. AB - Quantum dots (QDs) have attracted increasing attention due to their unique physical and chemical properties. This article introduces recent advances in using QDs' photoluminescence (PL) for in vitro and intracellular sensing analytes, in particular ions, and biomolecules from the last 3 years. Different sensing strategies are demonstrated and compared for increasing the detecting/sensing selectivity. The perspectives for in vitro and intracellular sensing based on QDs' PL are also discussed. PMID- 20306181 TI - Advances in fast electrophoretic separations based on short capillaries. AB - Capillary electrophoretic separations performed in short capillaries under high field strengths have recently emerged as a promising alternative to chip-based separations. However, the injection and detection approaches have to be adapted appropriately to enable high-throughput determinations. This paper addresses current challenges and trends in this field of research. PMID- 20306180 TI - Validation of a two-dimensional gas chromatography mass spectrometry method for the simultaneous quantification of cannabidiol, Delta(9)-tetrahydrocannabinol (THC), 11-hydroxy-THC, and 11-nor-9-carboxy-THC in plasma. AB - A sensitive analytical method for simultaneous quantification of sub-nanogram concentrations of cannabidiol (CBD), Delta(9)-tetrahydrocannabinol (THC), 11 hydroxy-THC (11-OH-THC), and 11-nor-9-carboxy-THC (THCCOOH) in plasma is presented for monitoring cannabinoid pharmacotherapy and illicit cannabis use. Analytes were extracted from 1 mL plasma by solid-phase extraction, derivatized with N,O-bis(trimethylsilyl) trifluoroacetamide with 1% trimethylchlorosilane, and analyzed by two-dimensional gas chromatography mass spectrometry (2D-GCMS) with cryofocusing. The lower calibration curve was linear from 0.25-25 ng/mL for CBD and THC, 0.125-25 ng/mL for 11-OH-THC and 0.25-50 ng/mL for THCCOOH. A second higher linear range from 5-100 ng/mL, achieved through modification of injection parameters, was validated for THC, 11-OH-THC, and THCCOOH and was only implemented if concentrations exceeded the lower curve upper limit of linearity. This procedure prevented laborious re-extraction by allowing the same specimen to be re-injected for quantification on the high calibration curve. Intra- and inter assay imprecision, determined at four quality control concentrations, were or=72.9% for all analytes. Analytes were stable when stored at 22 degrees C for 16 h, 4 degrees C for 48 h, after three freeze-thaw cycles at 20 degrees C and when stored on the autosampler for 48 h. This sensitive and specific 2D-GCMS assay provides a new means of simultaneously quantifying CBD, THC and metabolite biomarkers in clinical medicine, forensic toxicology, workplace drug testing, and driving under the influence of drugs programs. PMID- 20306182 TI - Colloquium Spectroscopicum Internationale XXXVI, Budapest (Hungary), August 30 September 3, 2009. PMID- 20306184 TI - Single-dose, multiple-dose, and population pharmacokinetics of pantoprazole in neonates and preterm infants with a clinical diagnosis of gastroesophageal reflux disease (GERD). AB - PURPOSE: The pharmacokinetic profile of pantoprazole granules was assessed in neonates and preterm infants with gastroesophageal reflux disease (GERD) in a multicenter, randomized, open-label trial. METHODS: Patients were randomly assigned to either the pantoprazole 1.25 mg (approx. 0.6 mg/kg) or 2.5 mg (approx. 1.2-mg/kg) group and treated for > or =5 consecutive days. Blood was sampled either at 0, 2, 8, and 18 h postdose or at 0, 1, 4, and 12 h postdose on day 1 and at 3 and 6 h postdose after > or =5 consecutive doses. Cytochrome P450 2C19 (CYP2C19) and CYP3A4 genotypes were determined. Safety was monitored. Population pharmacokinetics (popPK) analyses were conducted using nonlinear mixed effects modeling. RESULTS: The popPK modeling of the pantoprazole 1.25 mg and 2.5 mg groups obtained mean (+/-standard deviation) estimates for the area under the plasma concentration versus time curve (AUC) of 3.54 (+/-2.82) and 7.27 (+/-5.30) microg h/mL, respectively, and mean estimates for half-life of 3.1 (+/-1.5) and 2.7 (+/-1.1) h, respectively. Pantoprazole did not accumulate following multiple dose administration. The two patients with the CYP2C19 poor metabolizer genotype had a substantially higher AUC than extensive metabolizers. No safety-related discontinuations occurred. CONCLUSIONS: In preterm infants and neonates, pantoprazole granules were generally well tolerated, mean exposures with pantoprazole 2.5 mg were slightly higher than that in adults who received 40 mg. While the half-life was longer, accumulation did not occur. PMID- 20306185 TI - Effect of metronidazole on the pharmacokinetics of fexofenadine, a P-glycoprotein substrate, in healthy male volunteers. AB - OBJECTIVE: Metronidazole has been reported to cause various drug interactions when co-administered with certain drugs. One possible mechanism for this action is through an inhibition of P-glycoprotein (P-gp). We have assessed the possible inhibitory effects of metronidazole on P-gp-mediated drug disposition in healthy subjects using fexofenadine as a P-gp substrate. METHODS: This was a randomized, placebo-controlled, open-label, two-way crossover study involving 12 healthy male volunteers who were treated with metronidazole 500 mg or placebo three times daily for 7 days. On day 7, a single dose of fexofenadine 120 mg was given orally. Plasma levels of fexofenadine were measured and its pharmacokinetics assessed. RESULTS: Metronidazole did not affect the plasma concentration profiles and the pharmacokinetics of fexofenadine. The area under the time versus concentration curve of fexofenadine in the metronidazole phase (2075.7 ng h/mL) was similar to that of the placebo phase (1999.2 ng h/mL) (P = 0.356). Additionally, metronidazole did not affect the maximum plasma levels of fexofenadine (304.4 ng/mL for placebo vs. 293.2 ng/mL for metronidazole) (P = 0.423). The elimination half-life and oral clearance of fexofenadine were not affected by metronidazole treatment. CONCLUSION: These results show that metronidazole did not have any inhibitory effect on the pharmacokinetics of fexofenadine. The results of the present study provide evidence that metronidazole does not act as an inhibitor of P-gp-mediated disposition in humans. PMID- 20306186 TI - Enhancement of keratinolytic activity of a thermophilic subtilase by improving its autolysis resistance and thermostability under reducing conditions. AB - WF146 protease, a thermophilic subtilase from thermophile Bacillus sp. WF146, suffers excessive autolysis in the presence of reducing agents. In this report, two autolytic sites of WF146 protease were modified by site-directed mutagenesis. The introduction of prolines into the autolytic sites increased the autolysis resistance of the enzyme under reducing conditions. The double mutant N63P/A66P displayed a 2.8-fold longer half-life at 80 degrees C and higher hydrolytic activities than wild-type enzyme toward soluble (casein) and insoluble (keratin azure) substrates at high temperatures. In the presence of reducing agents, N63P/A66P was able to degrade feather at 80 degrees C ( approximately 3 h), with hydrolysis efficiency comparable to that of proteinase K at 50 degrees C ( approximately 24 h). Meanwhile, the mutant N63P/A66P had the ability to hydrolyze PrP(Sc)-like prion protein at high temperatures. In virtue of these properties, N63P/A66P is of great interest to be used in recycling of keratinous wastes, such as feather, and disinfection of medical apparatus. In addition, our study may provide useful information needed to explore keratinolytic potential of thermophilic subtilases, even if they are produced by non-keratinolytic microorganisms. PMID- 20306187 TI - Heterologous expression, characterization and site-directed mutagenesis of cutinase CUTAB1 from Alternaria brassicicola. AB - The cutinase CUTAB1 was cloned from a cutin induced culture of Alternaria brassicicola and heterologously expressed in Pichia pastoris under the control of the methanol-inducible AOX1 promoter. From a 400-ml culture, 36 mg of purified recombinant enzyme were obtained. Biochemical characterization revealed highest catalytic activity of the enzyme at 40 degrees C and pH 7-9 using p-nitrophenyl palmitate (p-NPP) as substrate. Among several fatty acid methyl and ethyl esters, glycerol esters and p-nitrophenyl esters tested, CUTAB1 showed highest activity towards tributyrin (3,302 +/- 160 U mg(-1)) and the activity decreased with increase in chain length of the investigated esters. Lowest activity was found for p-NPP. Replacing Leu80, Leu181 and Ile183, respectively, by the smaller alanine in the hydrophobic binding loop of CUTAB1, drastically reduced the overall activity of the enzyme. On the other hand, mutation A84F located in the small helical flap of CUTAB1 significantly increased the activity of the enzyme towards longer chain substrates like p-NPP. PMID- 20306188 TI - Alcohol dehydrogenase of acetic acid bacteria: structure, mode of action, and applications in biotechnology. AB - Pyrroquinoline quinone-dependent alcohol dehydrogenase (PQQ-ADH) of acetic acid bacteria is a membrane-bound enzyme involved in the acetic acid fermentation by oxidizing ethanol to acetaldehyde coupling with reduction of membranous ubiquinone (Q), which is, in turn, re-oxidized by ubiquinol oxidase, reducing oxygen to water. PQQ-ADHs seem to have co-evolved with the organisms fitting to their own habitats. The enzyme consists of three subunits and has a pyrroloquinoline quinone, 4 heme c moieties, and a tightly bound Q as the electron transfer mediators. Biochemical, genetic, and electrochemical studies have revealed the unique properties of PQQ-ADH since it was purified in 1978. The enzyme is unique to have ubiquinol oxidation activity in addition to Q reduction. This mini-review focuses on the molecular properties of PQQ-ADH, such as the roles of the subunits and the cofactors, particularly in intramolecular electron transport of the enzyme from ethanol to Q. Also, we summarize biotechnological applications of PQQ-ADH as to enantiospecific oxidations for production of the valuable chemicals and bioelectrocatalysis for sensors and fuel cells using indirect and direct electron transfer technologies and discuss unsolved issues and future prospects related to this elaborate enzyme. PMID- 20306189 TI - Strains of internal biofilm in aerobic granular membrane bioreactors. AB - This study isolated strains in suspended liquor, the surface fouling layer, and biofilm inside hollow-fiber membranes of a membrane bioreactor (MBR); analyzed their distributions, sizes, surface charges, and growth behaviors; and determined the quantities of extracellular polymeric substances (EPS) secreted by these strains under different organic loadings. Three strains, which may penetrate the microfiltration membranes, were close relatives of the Ralstonia mannitolilytica strain SDV (GenBank Accession No. GU451066), Arthrobacter sp. BJQ-2 (GenBank Accession No. GU451067), and Actinobacterium DS3 (GenBank Accession No. GU451068). Among these three strains, only Arthrobacter sp. developed an internal biofilm. The relatively short length of Arthrobacter sp. minimizes resistance to cells moving through the membrane matrix, thereby enhancing its ability to build a biofilm in the interior surface of membranes. PMID- 20306190 TI - Applications of quorum sensing in biotechnology. AB - Many unicellular microorganisms use small signaling molecules to determine their local concentration. The processes involved in the production and recognition of these signals are collectively known as quorum sensing (QS). This form of cell cell communication is used by unicellular microorganisms to co-ordinate their activities, which allows them to function as multi-cellular systems. Recently, several groups have demonstrated artificial intra-species and inter-species communication through synthetic circuits which incorporate components of bacterial QS systems. Engineered QS-based circuits have a wide range of applications such as production of biochemicals, tissue engineering, and mixed species fermentations. They are also highly useful in designing microbial biosensors to identify bacterial species present in the environment and within living organisms. In this review, we first provide an overview of bacterial QS systems and the mechanisms developed by bacteria and higher organisms to obstruct QS communications. Next, we describe the different ways in which researchers have designed QS-based circuits and their applications in biotechnology. Finally, disruption of quorum sensing is discussed as a viable strategy for preventing the formation of harmful biofilms in membrane bioreactors and marine transportation. PMID- 20306191 TI - Proteomic characterization of lignocellulose-degrading enzymes secreted by Phanerochaete carnosa grown on spruce and microcrystalline cellulose. AB - Proteins secreted by the white-rot, softwood-degrading fungus Phanerochaete carnosa during growth on cellulose and spruce were analyzed using tandem mass spectrometry and de novo sequencing. Homology-driven proteomics was applied to compare P. carnosa peptide sequences to proteins in Phanerochaete chrysosporium using MS BLAST and non-gapped alignment. In this way, 665 and 365 peptides from cellulose and spruce cultivations, respectively, were annotated. Predicted activities included endoglucanases from glycoside hydrolase (GH) families 5, 16, and 61, cellobiohydrolases from GH6 and GH7, GH3 beta-glucosidases, xylanases from GH10 and GH11, GH2 beta-mannosidases, and debranching hemicellulases from GH43 and CE15. Peptides corresponding to glyoxal oxidases, peroxidases, and glycopeptides that could participate in lignin degradation were also detected. Overall, predicted activities detected in extracellular filtrates of cellulose and spruce cultures were similar, suggesting that the adaptation of P. carnosa to growth on lignocellulose might result from fine tuning the expression of similar enzyme families. PMID- 20306193 TI - Editorial. Your new Editor-in-Chief. PMID- 20306192 TI - Possible mistakes in prediction of bone maturation in fibular hemimelia by Moseley chart. AB - The purpose of this study was to establish a nomogram in order to predict limb length discrepancies in children with unilateral fibular hemimelia more accurately. In 31 children with unilateral fibular hemimelia the femoral-tibial length and skeletal age were determined an average of seven times per case by sequential radiographs during growth. From the data, a skeletal age nomogram was developed which shows a steeply declining mean skeletal age pattern in unilateral fibular hemimelia (the slope in girls was -0.59 and in boys -0.64). This nomogram crosses the normal mean skeletal age line of the Moseley straight-line graph at 10.5 years in girls and at 12 years in boys, and continues to decline until maturity. The results demonstrate an abnormal skeletal maturation process in patients with unilateral fibular hemimelia. The consistently declining steep skeletal age nomogram in unilateral fibular hemimelia makes prediction of skeletal maturity and limb length discrepancy inaccurate by the standard predictive methods particularly when using early skeletal ages. The skeletal age nomogram from our data determines skeletal maturation in children with unilateral fibular hemimelia more accurately, and allows a correct prediction of limb length discrepancy. PMID- 20306194 TI - The histone deacetylase inhibitor valproic acid sensitizes human and canine osteosarcoma to doxorubicin. AB - PURPOSE: Osteosarcoma (OS) remains an incurable and ultimately fatal disease in many patients, and novel forms of therapy are needed. Improved models of OS that more closely mimic human disease would provide more robust information regarding the utility of novel therapies. Spontaneous OS in dogs may provide such a model. Pharmacologic inhibition of histone deacetylase (HDAC) enzymes has a variety of anti-tumor effects but may demonstrate the most utility when utilized in combination with standard cytotoxic therapies. We sought to determine the in vitro and in vivo effects of the HDAC inhibitor valproic acid (VPA) on doxorubicin (DOX) sensitivity in canine and human OS. METHODS: We evaluated the in vitro anti-proliferative and apoptotic effects of VPA/DOX combination treatment, alterations in histone acetylation and nuclear DOX accumulation resulting from VPA treatment, and the in vivo efficacy of combination therapy in a xenograft model. RESULTS: Treatment of canine and human OS cell lines with clinically achievable VPA concentrations resulted in increased histone acetylation but modest anti-proliferative effects. Pre-incubation with VPA followed by doxorubicin (DOX) resulted in significant growth inhibition and potentiation of apoptosis, associated with a dose-dependent increase in nuclear DOX accumulation. The combination of VPA and DOX was superior to either monotherapy in a canine OS xenograft model. CONCLUSION: These results demonstrate a rationale for the addition of HDAC inhibitors to current protocols for the treatment of OS and illustrate the similarities in response to HDAC inhibitors between human and canine OS, lending further credibility to the canine OS model. PMID- 20306195 TI - Pharmacokinetic and pharmacodynamic study of two doses of bortezomib in patients with relapsed multiple myeloma. AB - PURPOSE: Characterize bortezomib pharmacokinetics/pharmacodynamics in relapsed myeloma patients after single and repeat intravenous administration at two doses. METHODS: Forty-two patients were randomized to receive bortezomib 1.0 or 1.3 mg/m(2), days 1, 4, 8, 11, for up to eight 21-day treatment cycles (n = 21, each dose group). Serial blood samples for pharmacokinetic/pharmacodynamic analysis were taken on days 1 and 11, cycles 1 and 3. Observational efficacy and safety data were collected. RESULTS: Twelve patients in each dose group were evaluable for pharmacokinetics/pharmacodynamics. Plasma clearance decreased with repeat dosing (102-112 L/h for first dose; 15-32 L/h following repeat dosing), with associated increases in systemic exposure and terminal half-life. Systemic exposures of bortezomib were similar between dose groups considering the relatively narrow dose range and the observed pharmacokinetic variability, although there was no readily apparent deviation from dose-proportionality. Blood 20S proteasome inhibition profiles were similar between groups with mean maximum inhibition ranging from 70 to 84% and decreasing toward baseline over the dosing interval. Response rate (all 42 patients) was 50%, including 7% complete responses. The safety profile was consistent with the predictable and manageable profile previously established; data suggested milder toxicity in the 1.0 mg/m(2) group. CONCLUSIONS: Bortezomib pharmacokinetics change with repeat dose administration, characterized by a reduction in plasma clearance and associated increase in systemic exposure. Bortezomib is pharmacodynamically active and tolerable at 1.0 and 1.3 mg/m(2) doses, with recovery toward baseline blood proteasome activity over the dosing interval following repeat dose administration, supporting the current clinical dosing regimen. PMID- 20306197 TI - Winter as a nutritional bottleneck for North American porcupines (Erethizon dorsatum). AB - North American porcupines are distributed across a wide variety of habitats where they consume many different species of plants. Winter is a nutritional bottleneck for northern populations, because porcupines remain active when environmental demands are high and food quality is low. We used captive porcupines to examine physiological responses to low-quality diets at high energy demands during winter at ambient temperatures as low as -39 degrees C. We did not observe an endogenous pattern of body mass gain or loss when porcupines were fed a low nitrogen diet (1.1% dry matter) ad libitum through winter. Dry matter intake declined from 43.6 to 14.6 g kg(-0.75) d(-1) even though ambient temperatures declined from -3 to 30 degrees C, which indicates a seasonal decrease in metabolic rate. Porcupines consuming white spruce needles maintained digestive efficiency for energy (61%) and neutral detergent fiber (NDF) (50%). However, low requirements for energy (398 kJ kg(-0.75) d(-1)) and nitrogen (209 mg kg(-0.75) d(-1)) minimized the loss of body mass when intakes were low and plant toxins increased urinary losses of energy and nitrogen. Porcupines were also able to tolerate low intakes of sodium, even when dietary potassium loads were high. Porcupines use a flexible strategy to survive winter: low requirements are combined with a high tolerance for dietary imbalances that minimize the use of body stores when demands exceed supply. However, body stores are rapidly restored when conditions allow. Porcupines posses many physiological abilities similar to specialist herbivores, but retain the ability of a generalist to survive extreme conditions by using a variety of foods. PMID- 20306198 TI - Unicondylar knee replacement with a new tensioner device: clinical results of a multicentre study on 168 cases. AB - INTRODUCTION: Ligament balancing is an established surgical technique in total knee arthroplasty with good clinical results. A similar technique for unicondylar knee arthroplasty was developed. The aim of this study was to asses the outcomes of a unicondylar knee replacement implanted with a ligament tensor. MATERIALS AND METHODS: A prospective multicentre study of 168 medial compartment unicondylar knee prosthesis with a minimum follow-up of 2 years. Clinically, the knee society score was recorded. For subjective assessment, the visual analogue scale (VAS) for pain and satisfaction was used. Radiographic analysis was performed to determine radiolucent lines. The surgical technique was based on a ligament orientated procedure. With this technique, the femoral orientation, flexion/extension gaps and limb alignment is determined with a unique ligament tensor. RESULTS: The total KSS increased from 110.9 +/- 27.5 points preoperative to 176.5 +/- 21.1 points after 24 months. VAS for pain decreased from 6.0 +/- 1.9 preoperative to 2.8 +/- 1.7 after 24 months. VAS for satisfaction increased in the same period from 4.3 +/- 1.9 to 8.9 +/- 1.7. Four tibia implants had thin continuous radiolucent lines. Nine adverse events are reported. One patient died of unrelated causes. Five polyethylene inlays dislocated, one of five dislocated due to a fall. Three unicondylar knee prostheses were revised to a total knee arthroplasty, one because of undiagnosed pain, one for infection and one for femoral component malalignment. CONCLUSION: We have demonstrated the efficacy of a tension-controlled ligament-balanced surgical technique for unicompartmental knee prosthesis that gives satisfying and reproducible short-term results. PMID- 20306199 TI - Rare complication after VAC-therapy in the treatment of deep sore ulcers in a paraplegic patient. AB - The VAC-therapy is a safe, easy, and effective therapy for the management of chronic wounds. Known advantages of the VAC technique are the quicker wound healing by stimulating the blood flow, the formation of granulation tissue, angiogenesis, and cell proliferation. The use of negative pressure treatment can decrease the number of dressing changes and length of hospital stay. However, some related complications after and during VAC therapy have been described. We here describe a rare complication during the treatment of severe os ischium sore with VAC therapy, which has not been reported in the literature yet. We report about a 43-year-old paraplegic patient, referred to our clinic from a regional hospital where he had been admitted 2 months earlier, presenting with a necrotizing fasciitis after VAC therapy during the treatment of fourth grade os ischium sore. After operative debridement and long-term antibiotics with Ciprofloxacin soft tissue closure was performed using a myocutaneous tensor fascia lata flap. Temporary stabilization was achieved by a triangle external fixateur attached to the right femur and the pelvis. After 1 week the tapping point of the muscle flap could be covered with local skin mesh-graft from the right calf as a donor site. The patient was mobilized in a wheelchair and was discharged home 3 months after admission. The VAC technique is a safe, easy, and effective means in chronic wound care management. However, the described rare complication should be kept in mind. The clinical management of VAC therapy requires a distinct indication and close clinical monitoring by experienced medical professionals. The use of VAC therapy in fourth grade sores may have deleterious consequences for the patient. PMID- 20306200 TI - Correlation of serum BDNF levels with hippocampal volumes in first episode, medication-free depressed patients. AB - The hippocampus seems to be affected in MDD, and brain-derived neurotrophic factor (BDNF) has positive effects on neurogenesis within the hippocampus. Although there are inconsistencies among study results, a smaller hippocampal volume in depressed patients is thought to be related to the pathophysiology of the disease. We looked at the correlation between serum BDNF (sBDNF) levels and hippocampal volumes (HCV) of first-episode MDD patients (18 female, 7 male; mean age = 32.1 +/- 9.3) and healthy controls (17 female, 5 male; mean age = 29.7 +/- 6.4). Region of interest analysis was conducted on the images acquired via MRI. sBDNF levels and HCV correlated only in the MDD group (right: r = 0.46, P = 0.02; left: r = 0.47, P = 0.02); however, HCV did not differ between MDD patients and healthy controls (right: F = 2.45, df = 1.46, P > 0.05; left: F = 0.05, df = 1.46, P > 0.05). BDNF may be a factor underlying HCV differences between MDD and healthy control subjects, which become apparent as severe and multiple episodes are experienced. PMID- 20306201 TI - Controlling precise movement with stochastic signals. AB - In a noisy system, such as the nervous system, can movements be precisely controlled as experimentally demonstrated? We point out that the existing theory of motor control fails to provide viable solutions. However, by adopting a generalized approach to the nonconvex optimization problem with the Young measure theory, we show that a precise movement control is possible even with stochastic control signals. Numerical results clearly demonstrate that a considerable significant improvement of movement precisions is achieved. Our generalized approach proposes a new way to solve optimization problems in biological systems when a precise control is needed. PMID- 20306202 TI - Mappings between a macroscopic neural-mass model and a reduced conductance-based model. AB - We present two alternative mappings between macroscopic neuronal models and a reduction of a conductance-based model. These provide possible explanations of the relationship between parameters of these two different approaches to modelling neuronal activity. Obtaining a physical interpretation of neural-mass models is of fundamental importance as they could provide direct and accessible tools for use in diagnosing neurological conditions. Detailed consideration of the assumptions required for the validity of each mapping elucidates strengths and weaknesses of each macroscopic model and suggests improvements for future development. PMID- 20306203 TI - The Drosophila neural lineages: a model system to study brain development and circuitry. AB - In Drosophila, neurons of the central nervous system are grouped into units called lineages. Each lineage contains cells derived from a single neuroblast. Due to its clonal nature, the Drosophila brain is a valuable model system to study neuron development and circuit formation. To better understand the mechanisms underlying brain development, genetic manipulation tools can be utilized within lineages to visualize, knock down, or over-express proteins. Here, we will introduce the formation and development of lineages, discuss how one can utilize this model system, offer a comprehensive list of known lineages and their respective markers, and then briefly review studies that have utilized Drosophila neural lineages with a look at how this model system can benefit future endeavors. PMID- 20306204 TI - Expression and immune response analysis of Schistosoma japonicum VAL-1, a homologue of vespid venom allergens. AB - Many parasites such as trematodes and nematodes have been found to express members of a gene family variously termed as venom allergen-like protein (VAL) or sperm-coating protein (SCP)-like protein. The molecular functions of these proteins remain unclear. We isolated the corresponding gene from Schistosoma japonicum, which we designated as Sj-VAL-1. The cDNA of Sj-VAL-1 contains an open reading frame encoding 221 amino acids, the first 25 residues being a putative secretion signal. RT-PCR analysis confirmed that Sj-VAL-1 was transcribed mainly in cercariae and eggs stages. Western blot analysis indicated that Sj-VAL-1 protein was an egg excretory-secretory products (ES products). Immunofluorescence showed it was secreted by eggs, head gland, and penetration glands of cercariae. In S. japonicum-infected mice, Sj-VAL-1-specific antibody significantly increased 6 weeks after infection and a higher level of IgG1 antibody contrast to IgG2a antibody indicated that a polarized Th2 immune response could be induced by Sj VAL-1. These findings suggest that Sj-VAL-1 must play a role in the interaction between parasite and host. Its role as a potential modulator of immune function or as a pathogenic factor of granuloma formation in schistosomiasis needs further study. PMID- 20306205 TI - Evaluation of medicinal plant extracts against blood-sucking parasites. AB - The present study was based on assessments of the antiparasitic activities to determine the efficacies of acetone, chloroform, ethyl acetate, hexane, and methanol dried leaf, flower, and seed extracts of Cassia auriculata L., Rhinacanthus nasutus KURZ., Solanum torvum Swartz, Terminalia chebula Retz., and Vitex negundo Linn. were tested against larvae of cattle tick Rhipicephalus (Boophilus) microplus Canestrini, 1887 (Acari: Ixodidae), adult of Haemaphysalis bispinosa Neumann, 1897 (Acarina: Ixodidae), hematophagous fly Hippobosca maculata Leach (Diptera: Hippoboscidae), nymph of goat-lice Damalinia caprae Gurlt (Trichodectidae), and adult sheep parasite Paramphistomum cervi Zeder, 1790 (Digenea: Paramphistomatidae). All plant extracts showed moderate parasitic effects after 24 h of exposure at 3,000 ppm; however, the highest parasite mortality was found in leaf ethyl acetate, flower methanol of C. auriculata, leaf and seed methanol of S. torvum, seed acetone of T. chebula, and leaf hexane extracts of V. negundo against the larvae of R. microplus (LC(50) = 335.48, 309.21, 297.43, 414.99, 167.20, and 611.67 ppm; LC(90) = 1571.58, 1111.82, 950.98, 1243.64, 595.31, and 1875.50 ppm), the leaf and flower methanol of R. nasutus, leaf and seed methanol of S. torvum, and seed methanol extracts of T. chebula against the nymph of D. caprae (LC(50) = 119.26,143.10,164.93,140.47, and 155.98 ppm; LC(90) = 356.77, 224.08, 546.20, 479.72, and 496.06 ppm), the leaf methanol of R. nasutus, leaf and seed methanol of S.torvum, and seed acetone of T. chebula against the adult of H. bispinosa (LC(50) = 333.15, 328.98, 312.28, and 186.46 ppm; LC(90) = 1056.07, 955.39, 946.63, and 590.76 ppm), the leaf methanol of C. auriculata, the leaf and flower methanol of R. nasutus, the leaf ethyl acetate of S. torvum against the H. maculata (LC(50) = 303.36, 177.21, 204.58, and 211.41 ppm; LC(90) = 939.90, 539.39, 599.43, and 651.90 ppm), and the leaf acetone of C. auriculata, the flower methanol of R. nasutus, the seed methanol of S. torvum, and the seed acetone of T. chebula were tested against the adult of P. cervi (LC(50) = 180.54, 168.59, 200.89, and 87.08 ppm; LC(90) = 597.51, 558.65, 690.37, and 433.85 ppm), respectively. Therefore, this study provides first report on the veterinary parasitic activity of plant extracts from Southern India. PMID- 20306206 TI - Survey of Naegleria and its resisting bacteria-Legionella in hot spring water of Taiwan using molecular method. AB - Naegleria is a free-living amoebae existing in soil and aquatic environments. Within the genus Naegleria, N. fowleri is most recognized as potential human pathogen causing primary amoebic meningoencephalitis (PAM). Furthermore, the Naegleria spp. can serve as vehicles for facultative pathogens, such as Legionella. In this study, we identified Naegleria and Legionella based on the PCR amplification with a genus-specific primer pair and investigated the distribution of Naegleria and Legionella at five spring recreation areas in Taiwan. In this study of hot spring and other water sources in Taiwan, five Naegleria spp. were detected in 15 (14.2%) of the water samples. The most frequently detected was N. lovaniensis (n = 6), followed by N. australiensis (n = 5), and then N. clarki (n = 2). N. americana and N. pagei were detected once, respectively. The pathogenic species N. fowleri was not detected; however, N. australiensis considered to be a potential pathogen species in humans was found. Legionella spp., an endosymbiont of Naegleria, was detected in 19 (17.9%) of the water samples in this study. Overall, 5.7% of the water samples contained both Naegleria and Legionella. The Legionella spp. identified were L. pneumophila and L. erythra. Results of this survey confirm the existence of Naegleria and Legionella in Taiwan spring recreation areas. It should be considered a potential threat for health associated with human activities in spring recreation areas of Taiwan. PMID- 20306207 TI - Effect of fingerroot on reducing inflammatory cells in hamster infected with Opisthorchis viverrini and N-nitrosodimethylamine administration. AB - The active compound in fingerroot is effective in the treatment of many inflammatory diseases. The aim of our present study was to evaluate the efficacy of fingerroot on reducing histopathological changes in hamsters that were infected with the liver fluke Opisthorchis viverrini or were administered N nitrosodimethylamine (NDMA), and then treated with fingerroot. Light microscopic observation and liver function tests for alanine transaminase (ALT), alkaline phosphatase (ALP), and direct bilirubin were investigated. The results of histopathological changes show that fingerroot has anti-inflammatory properties- in the case of N-nitrosodimethylamine administration on day 30--by reducing the aggregation of inflammatory cells surrounding the hepatic bile ducts, which correlates with a decreased serum ALT level. The decrease of direct bilirubin levels in hamsters treated with fingerroot suggests that fingerroot may enhance biliary contraction. The present study found that fingerroot clearly reduces the inflammatory cells in hamsters that were administered NDMA, but not in the case of O. viverrini infection. This finding suggests that fingerroot has anti inflammatory property, but not in the case of hamster opisthorchiasis. PMID- 20306209 TI - Tetramerization of white spot syndrome virus envelope protein VP33 and its interaction with VP24. AB - VP33, also termed VP281, VP37 or VP36B, is a minor envelope protein of white spot syndrome virus (WSSV). Because of its low abundance and lack of a transmembrane domain, we hypothesized that VP33 is likely to be attached to the viral envelope by interaction with other envelope proteins. In this study, we employed far western blotting and pull-down assays to demonstrate that VP33 interacts with itself, as well as with VP24, which is one of the four major viral envelope proteins. Moreover, a gel-filtration analysis was performed to show that this self-interaction led to the formation of stable VP33 tetramers. These results implied that VP33 tetramers were anchored to the viral envelope through interaction with VP24, suggesting that VP33 may participate in the formation of the WSSV envelope. PMID- 20306208 TI - Encystation--survival of Blastocystis hominis in immunocompetent mice abdomen cavity. AB - Human Blastocystis hominis were isolated from diarrhea patients' feces and cultured in vitro. Then the cultures were inoculated intraperitoneally to laboratory mice. The B. hominis in living mice were collected and inoculated again to healthy mice. The B. hominis showed dose-dependent pathogenicity in the primary inoculation. No pathogenicity was observed in the secondary inoculation. The protozoan existed in the living mice abdomen cavity for more than 6 months and the cyst was the only form. These results showed that encystation enable the parasite to avoid the immune attack in competent host and simultaneously decrease the pathogenicity to host. Intraperitoneal inoculation to laboratory mice is a good method to maintain and propagate B. hominis. This is also a good model to study the interaction of B. hominis and immune system. PMID- 20306210 TI - Identification and characterization of novel hepatitis B virus subgenotype C10 in Nusa Tenggara, Indonesia. AB - Six novel subgenotypes (B7, B8, C6, C8, C9, and D6) within three hepatitis B virus (HBV) genotypes (B-D) were recently identified in Indonesia. To further characterize HBV in this country, 18 HBV-viremic samples obtained from blood donors in Nusa Tenggara, Indonesia, were subjected to phylogenetic analysis of an 1.6-kb partial or full-length sequence. Thirteen HBV isolates were classified into genotype B with four distinct subgenotypes [B3 (n = 2), B5 (n = 1), B7 (n = 4), and B8 (n = 6)], followed by 4 HBV isolates of genotype C (HBV/C); the remaining one isolate was of D (D1). As for the four HBV/C isolates, one isolate segregated into subgenotype C1, and two into C2. The remaining HBV/C isolate [C0901177(NT3)] differed from reported HBV/C isolates (C1-C9) by 4.6-7.7% over the entire genome and did not show evidence of recombination with any of the known HBV genotypes/subgenotypes, justifying its conclusive assignment into a novel subgenotype (C10) within genotype C. PMID- 20306211 TI - Identifying intimate partner violence (IPV) during the postpartum period in a Greek sample. AB - Research has highlighted the wide impact of intimate partner violence (IPV) and the public health role of community health professionals in detection of victimized women. The purpose of this study was to identify postpartum emotional and physical abuse and to validate the Greek version of the Women Abuse Screening Tool (WAST) along with its sensitivity and specificity. Five hundred seventy-nine mothers within 12 weeks postpartum were recruited from the perinatal care registers of the Maternity Departments of two public hospitals in Athens, Greece. Participants were randomly selected by clinic or shift. The WAST and the Partner Violence Screen (PVS) surveys were administered in random order to the mothers from September 2007 to January 2008. The WAST was compared with the PVS as a criterion standard. Agreement between the screening instruments was examined. The psychometric measurements that were performed included: two independent sample t tests, reliability coefficients, explanatory factor analysis using a Varimax rotation, and Principal Components Method. Confirmatory analysis-also called structural equation modeling-of principal components was conducted by Linear Structural Relations. A receiver operating characteristic (ROC) analysis was carried out to evaluate the global functioning of the scale. Two hundred four (35.6%) of the mothers screened were identified as experiencing IPV. Scores on the WAST correlated well with those on the PVS; the internal consistency of the WAST Greek version-tested using Cronbach's alpha coefficient-was found to be 0.926 and that of Guttman's split-half coefficient was 0.924. Our findings confirm the multidimensionality of the WAST, demonstrating a two-factor structure. The area under ROC curve (AUC) was found to be 0.824, and the logistic estimate for the threshold score of 0/1 fitted the model sensitivity at 99.7% and model specificity at 64.4%. Our data confirm the validity of the Greek version of the WAST in identifying IPV. The validated Greek WAST scale could be used for screening purposes in both clinical practice and research. PMID- 20306212 TI - Reinforcing a medical hypothesis with a new question: is there a subgroup of shrinking lungs syndrome that is induced by pleurisy in systemic lupus erythematosus and is this subgroup marked by anti-Ro/SSA? AB - Shrinking lungs syndrome (SLS) is a rare entity associated with autoimmune diseases and its underlying pathogenesis is still unclear. We describe a series of seven consecutive cases of SLS in systemic lupus erythematosus, all of them with serositis and six (85.7%) with anti-Ro/SSA antibodies. Our findings reinforce the hypothesis that SLS may be, in some cases, a consequence of diaphragmatic restriction due to pleuritic pain, and we suggest anti-Ro/SSA as a marker of this subgroup of SLS. PMID- 20306213 TI - Prolonged infections associated with antineutrophil cytoplasmic antibodies specific to proteinase 3 and myeloperoxidase: diagnostic and therapeutic challenge. AB - Chronic infections may mimic antineutrophil cytoplasmic antibody (ANCA) associated vasculitides (AAV). We investigated which markers may help in the diagnosis and the prognosis of infections associated with proteinase 3 (PR3) and myeloperoxidase (MPO)-ANCA. In this study (1993-2008)--with an average follow-up of 5.1 years--we compared 66 AAV patients with 17 PR3 and/or MPO-ANCA-positive patients with protracted bacterial (11/17) or viral (6/17) infections. Seven of 17 patients had subacute bacterial endocarditis (SBE), while six of 17 patients had various autoimmune manifestations of chronic hepatitis C virus (HCV) infection. We determined ANCA, antinuclear antibodies, anti-PR3, anti-MPO, anticardiolipin (aCL), antibeta 2 glycoprotein I (beta2-GP I), cryoglobulins, C3, and C4. Patients with infections were younger than AAV patients (p < 0.01). There was no difference in frequency of renal and skin lesions. AAV patients more frequently had pulmonary and nervous system manifestations (p < 0.01). Patients with infections more frequently had dual ANCA (high PR3, low MPO), aCL, anti beta2-GP I, cryoglobulins, and hypocomplementemia (p < 0.001). Immunosuppressive therapy (IST) was used in five 17 patients who had persistently high ANCA, cryoglobulinemia, and hypocomplementemia. There was no difference in frequency of lethality and renal failure in the two study groups. In patients who are PR3- and/or MPO-ANCA positive, SBE and HCV infection should be excluded. Although similar in renal and skin manifestations in comparison to AAV, only patients with infections developed multiple serological abnormalities. In patients with infections, concomitant presence of ANCA, cryoglobulins, and hypocomplementemia was associated with severe glomerulonephritis. The serological profile should be repeated after specific antimicrobial or surgical therapy, since some cases might require IST. PMID- 20306214 TI - Reproducibility of the Bath Ankylosing Spondylitis Indices of disease activity (BASDAI), functional status (BASFI) and overall well-being (BAS-G) in anti-tumour necrosis factor-treated spondyloarthropathy patients. AB - The Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), the Bath Ankylosing Spondylitis Function Index (BASFI) and the Bath Ankylosing Spondylitis Global Score (BAS-G) (ranges 0-10) have gained widespread in use as self-reported measures of disease activity, functional impairment and overall well-being in patients with ankylosing spondylitis and other spondyloarthropathies (SpA). In Denmark, BASDAI, BASFI and BAS-G are systematically used to monitor treatment response in patients treated with tumour necrosis factor (TNF) inhibitors. The purpose of the present study was to examine the reproducibility of the indices in anti-TNF-treated SpA patients already familiar with the use of the indices. Testing was performed twice on two different days (median interval 7 days, range 4-10 days) under standardised conditions in 26 out-clinic patients (median age 39 years, range 22-56 years). Limits of agreement were calculated as the 95% likely range for the difference between paired scores. Test-retest results were significantly intercorrelated with r (s) = 0.90 for BASDAI, 0.92 for BASFI and 0.74 for BAS-G. Limits of agreement for BASDAI, BASFI and BAS-G were +/-1.8, +/ 1.4 and +/-3.2, respectively. Reproducibility as expressed as the mean of individual standard deviations was significantly poorer for BAS-G than for BASDAI and BASFI (p < 0.01). Internal consistency reliability and construct validity of BASDAI and BASFI were acceptable. In conclusion, in a sample of anti-TNF-treated patients experienced with the use of BASDAI, BASFI and BAS-G, random measurement errors of the scores were not negligible. The finding should be considered when monitoring anti-TNF treatment in daily clinical practice. PMID- 20306215 TI - Can the quality of pearls from the Japanese pearl oyster (Pinctada fucata) be explained by the gene expression patterns of the major shell matrix proteins in the pearl sac? AB - For pearl culture, the pearl oyster is forced open and a nucleus is implanted into the gonad with a mantle graft. The outer mantle epithelial cells of the implanted mantle graft elongate and surrounding the nucleus a pearl sac is formed. Shell matrix proteins secreted by the pearl sac play an important role in the regulation of pearl formation. Recently, seven shell matrix proteins were identified from the pearl oyster Pinctada fucata. However, there is a paucity of information on the function of these proteins and their gene expression patterns. Our study aims to elucidate the relationship between pearl type, quality, and gene expression patterns of six shell matrix proteins (msi60, n16, nacrein, msi31, prismalin-14, and aspein) in the pearl sac based on real-time PCR analysis. After culturing for about 2 months, the pearl sac tissues were collected from 22 individuals: 12 with high quality (HP), nine with low quality (LP), and one with organic (ORG) pearl formation. The surface of each of the 12 HP pearls was composed only of a nacreous layer; in contrast, that of the nine LP pearls was composed of nacreous and prismatic layers. The six target gene expressions were detected in all individuals. However, delta threshold cycle (DeltaC(T)) for msi31 was significantly higher in the HP than in the LP individuals (Mann-Whitney's U test, p=0.02). This means that the relative expression level of msi31, which constitutes the framework of the prismatic layer, was higher in the LP than in the HP individuals. PMID- 20306216 TI - Drag coefficient of a liquid domain in a two-dimensional membrane. AB - Using a hydrodynamic theory that incorporates a momentum decay mechanism, we calculate the drag coefficient of a circular liquid domain of finite viscosity moving in a two-dimensional membrane. We derive an analytical expression for the drag coefficient which covers the whole range of domain sizes. Several limiting expressions are discussed. The obtained drag coefficient decreases as the domain viscosity becomes smaller with respect to the outer membrane viscosity. This is because the flow induced in the domain acts to transport the fluid in the surrounding matrix more efficiently. PMID- 20306217 TI - Combination therapy with dexamethasone and osteoprotegerin protects against arthritis-induced bone alterations in antigen-induced arthritis of the rat. AB - OBJECTIVE: To investigate the influence of a combined therapy consisting of dexamethasone and osteoprotegerin (OPG) on bone alterations and disease activity in antigen-induced arthritis (AIA) in the rat. METHODS: AIA rats received dexamethasone (0.25 mg kg(-1) day(-1), i.p.), OPG (2.5 mg kg(-1) day(-1), i.p.), or a combination of both at regular intervals for 21 consecutive days. At the end of the treatment, bone structure was analyzed by histomorphometry. Primary spongiosa was measured using linear scanning. RESULTS: AIA led to significant periarticular and axial bone loss. Dexamethasone monotherapy substantially suppressed joint swelling without inhibiting bone loss of the secondary spongiosa, whereas OPG monotherapy showed no anti-inflammatory effect. Despite reduction of bone resorption, OPG did not inhibit AIA-induced bone loss. In contrast, the combination of dexamethasone and OPG not only produced an anti inflammatory effect, but also resulted in inhibition of periarticular and axial bone loss. OPG increased trabecular number of the primary spongiosa whilst combination therapy led to an increase in both trabecular number and trabecular width. CONCLUSION: The principle of combining a glucocorticoid together with inhibition of the receptor activator of NF-kappaB ligand (RANKL) may be an effective bone-saving therapy in rheumatoid arthritis. PMID- 20306218 TI - Docking study of the precursor peptide of mastoparan onto its putative processing enzyme, dipeptidyl peptidase IV: a revisit to molecular ticketing. AB - Stepwise-cleavage process of promastoparans to reach maturity was investigated theoretically by combining ab initio folding and unbounded docking. The comparison between the structures of the promastoparans both before and after docking were examined along with the hydrogen bonding interaction pattern between the dipetidyl peptidase IV (DPPIV) and promastoparans to reveal how the endpoint of this stepwise cleavage is recognized among these promastoparans with highly resemble amino acid sequences. The current approach of folding and docking study provides structural insight on the stepwise cleavage process. PMID- 20306219 TI - Comparison of the phytotoxic effects of usnic acid on cultures of free-living alga Scenedesmus quadricauda and aposymbiotically grown lichen photobiont Trebouxia erici. AB - The phytotoxic effects of the lichen secondary metabolite-usnic acid on cultures of free living alga-Scenedesmus quadricauda (UTEX 76) and aposymbiotically grown lichen photobiont Trebouxia erici (UTEX 911) were assessed. We found a relatively strong inhibition effect of usnic acid on the growth of alga Scenedesmus, accompanied by an increase of cell size, an alteration of assimilation pigment composition, followed by strong degradation of chlorophyll a, a decrease of chlorophyll a fluorescence, and an increase of reactive oxygen species in the cells. The content of soluble proteins remained a stable parameter. Phytotoxicity of usnic acid on cultures of Trebouxia photobiont was significantly lower. Usnic acid in lichens may act as an allochemical that controls the division of photobiont cells, thereby regulating the balance between the photobiont and mycobiont forming thallus. Higher tolerance to usnic acid in Trebouxia cultures may be an adaptation resulting from the long term co-evolution of these algae with fungi that produce secondary metabolites. PMID- 20306220 TI - Delayed or forgone care and dissatisfaction with care for children with special health care needs: the role of perceived cultural competency of health care providers. AB - To better understand if reported delayed/forgone care and dissatisfaction with care for children with special health care needs (CSHCN) are associated with the parent's perception of health care providers' cultural competency. National survey. Fifty United States and the District of Columbia yielding 750 families per state and District of Columbia with CSHCN <= 18 years participated in the 2005-06 National Survey of CSHCN. Outcome measures were delayed/forgone care in the past 12 months (yes or no) and dissatisfaction (very dissatisfied to very satisfied). Demographic/clinical characteristics and the parent's perception of health care providers' cultural competency were examined. Perception of cultural competency was defined by questions related to time spent with child, respect for family values, listening to the family, sense of partnership, and information provided. Delayed/forgone care and dissatisfaction with care were associated with perceived health care provider cultural competency. Parents whose children were older, whose children's condition affected their ability to do things, whose interviews were not conducted in English, and were from certain racial and ethnic groups reported more delayed or forgone care and were more dissatisfied with their children's health care. Delayed/forgone care and dissatisfaction with care were associated with perceived cultural competency of health care providers. This did not appear to differ consistently by racial or ethnic group. Further research using more refined instruments and longitudinal designs is needed to assess the effects of health care providers' cultural competency and other cultural factors on the delayed/forgone care for CSHCN and on the dissatisfaction with care of parents with CSHCN. PMID- 20306221 TI - Assessment of the Institute of Medicine recommendations for weight gain during pregnancy: Florida, 2004-2007. AB - We investigated the association between 2009 IOM recommendations and adverse infant outcomes by maternal prepregnancy body mass index (BMI). Birth outcomes for 570,672 women aged 18-40 years with a singleton full-term live-birth were assessed using 2004-2007 Florida live-birth certificates. Outcomes included large for-gestational-age (LGA) and small-for-gestational-age (SGA). Associations between gestational weight change and outcomes were assessed for 10 BMI groups by calculating proportions, and logistic regression modeling was used to produce adjusted odds ratios (aORs) to account for the effect of confounders. We created comparison categories below and above recommendations using 2009 IOM recommendations as a reference. Of importance, 41.6% of women began pregnancy as overweight and obese and 51.2% gained weight excessively during pregnancy on the basis of 2009 IOM recommendations. Proportions of LGA were higher among obese women and increased with higher weight gain. Compared with recommended weight gain, aORs for LGA were lower with less than recommended gain (aOR range: 0.27 0.77) and higher with more than recommended gain (aOR range: 1.27-5.99). However, SGA was less prevalent among obese women, and the proportion of SGA by BMI was similar with higher weight gain. Gain less than recommended was associated with increased odds of SGA (aOR range: 1.11-2.97), and gain greater than recommended was associated with decreased odds of SGA (aOR range: 0.38-0.83). Gestational weight gain influenced the risk for LGA and SGA in opposite directions. Minimal weight gain or weight loss lowered risk for LGA among obese women. Compared with 1990 IOM recommendations, 2009 recommendations include weight gain ranges that are associated with lower risk of LGA and higher risk of SGA. Awareness of these tradeoffs may assist with clinical implementation of the 2009 IOM gestational weight gain recommendations. However, our results did not consider other maternal and infant outcomes related to gestational weight gain; therefore, the findings should be interpreted with caution. PMID- 20306223 TI - Differential expression of Toll-like receptor 2 and 4 on peritoneal leukocyte populations from long-lived and non-selected old female mice. AB - The aim of the present study was to determine Toll-like receptor (TLR)-2 and TLR 4 membrane expression on the major peritoneal leukocyte populations throughout the aging process, including subjects that had achieved exceptional longevity. ICR (CD1) female mice of different ages: adult (44 +/- 4 weeks), old (69 +/- 4), very old (92 +/- 4) and extreme long-lived (125 +/- 4), were used. Peritoneal leukocytes were collected, and percentages of CD11b, CD11c, CD3CD4, CD3CD8 and CD19 cells present in the samples were analysed, as well as the expression of TLR 2 and TLR-4 on them, by flow cytometry. The results showed increased TLR expression on CD11b+ cells from animals at very old ages and especially in the extreme long-lived. Old subjects showed lower percentage of CD11c+ cells, but no age-related changes were found in the TLR expression on these cells. TLRs on CD3CD4+ and CD3CD8+ cells from very old animals were increased as compared to the adults, whereas long-lived subjects showed preserved levels. However, TLR expression on CD19+ cells was higher in long-lived individuals with respect to subjects at all the other younger ages. These data suggest that differential age related changes in the expression of TLR-2 and TLR-4 on leukocyte populations from long-lived and non-selected younger old mice could contribute to a different age-related immune remodelling in long-lived subjects, which could allow better preservation of their immune responses. PMID- 20306222 TI - Suitability of Daphnia similis as an alternative organism in ecotoxicological tests: implications for metal toxicity. AB - The acute toxicity of metals to Daphnia similis was determined and compared to other daphnid species to evaluate the suitability of this organism in ecotoxicology bioassays. To verify the performance D. similis in toxicity tests, we also investigated the effect of Pseudokirchneriella subcapitata at 1 x 10(5) and 1 x 10(6) cells ml(-1) on Cd and Cr acute toxicity to the cladoceran. Daphnid neonates were exposed to a range of chromium and cadmium concentrations in the absence and presence of the algal cells. Metal speciation calculations using MINEQL(+) showed that total dissolved metal concentrations in zooplankton culture corresponded to 96.2% free Cd and 100% free Cr concentrations. Initial total dissolved metal concentrations were used for 48 h-LC(50) determination. LC(50) for D. similis was 5.15 x 10(-7) mol l(-1) dissolved Cd without algal cells, whereas with 1 x 10(5) cells ml(-1), it was significantly higher (7.15 x 10(-7) mol l(-1) dissolved Cd). For Cr, the 48 h-LC(50) value of 9.17 x 10(-7) mol l(-1) obtained for the cladoceran in tests with 1 x 10(6) cells ml(-1) of P. subcapitata was also significantly higher than that obtained in tests without algal cells (5.28 x 10(-7) mol l(-1) dissolved Cr). The presence of algal cells reduced the toxicity of metals to D. similis, as observed in other studies that investigated the effects of food on metal toxicity to standard cladocerans. Comparing our results to those of literature, we observed that D. similis is as sensitive to metals as other standardized Daphnia species and may serve as a potential test species in ecotoxicological evaluations. PMID- 20306224 TI - Knowledge of cardiovascular health among Chinese, Korean and Vietnamese immigrants to the US. AB - Cardiovascular disease (CVD) is the leading cause of death among Asian Americans, the majority of whom are foreign-born. However, CVD and risk factor data is sparse for specific Asian immigrant populations. To assess knowledge and understanding of CVD and risk factors within Chinese, Korean and Vietnamese immigrant populations, we conducted eight focus groups of 77 participants between 36 and 84 years old. Participants correctly identified signs and symptoms for heart attacks while knowledge about stroke was incomplete. While poor diet, lack of exercise, older age, and high cholesterol were frequently discussed as risk factors, mechanisms perceived as contributing to heart disease were influenced primarily by non-Western paradigms. Non-Western remedies were discussed in detail among Chinese and Vietnamese participants. All participants desired more information, and identified barriers to effective communication with healthcare providers. A deeper understanding of beliefs and barriers faced by Asian immigrants can help guide health promotion efforts. PMID- 20306225 TI - A trajectory model for understanding and assessing health disparities in immigrant/refugee communities. AB - While numerous factors contributing to racial/ethnic health disparities have been identified, the clustering and interaction of these factors as a syndemic or trajectory has not been well-studied (Starfield in Soc Sci Med 64:1355-1362, 2007; Singer in Soc Sci Med 39(7):931-948, 1994). More importantly, for immigrant/refugee populations, the interaction of contributing factors is not documented adequately enough to provide a solid framework for planning, implementation and evaluation of interventions aimed at reducing disparities. In this paper, the authors draw from the literatures on health disparities and immigrant/refugee health, as well as direct program and research experience, to propose an approach for assessment of the diachronic interaction of ecological factors (a trajectory, or "diachronic ecology") contributing to health disparities among immigrant/refugee populations. It is our hope that this approach will contribute to the important effort to collect data supporting the development of interventions and policies that effectively address the dynamic processes through which health disparities are created, maintained, and changed. PMID- 20306226 TI - Long-term care residents' views about the contributions of Christian-based volunteers in Taiwan: a pilot study. AB - This pilot study explored the view from six long-term care residents on the contributions of religious volunteers. The findings suggest that religious volunteers may contribute to long-term care residents' religious or spiritual health more than non-religious volunteers. However, since religious volunteers lack professional training and competence to attend to patients' religious needs, they may not afford in-depth spiritual and religious services. Under certain conditions when qualified chaplains are not available, inadequate religious services performed by religious volunteers are still better than no such care at all. However, in order to provide this important aspect of holistic care, we propose that health care policy makers should pay more attention to this topic. PMID- 20306227 TI - Identification and characterization of class I chitinase in Panax ginseng C. A. Meyer. AB - The role of plant chitinases in protecting plants against a variety of fungal pathogens is well established. In the present study, a cDNA clone containing a class I chitinase (Chi-1) gene, designated as PgChi-1, has been isolated from the oriental medicinal plant Panax ginseng. PgChi-1 is predicted to encode a protein of 34.9 kDa consisting of 323 amino acid residues. PgChi-1 was found to be expressed constitutively in all of the studied organs of ginseng plant. Under various abiotic stress treatments including Cu, H2O2, mannitol, SA, JA, and NaCl, the expression of PgChi-1 in plantlets and hairy roots increased significantly compared to the control. When different parts of root were analyzed, maximum level was observed in taproot. In addition, levels of PgChi-1 expression were compared between healthy root and fungal, bacterial, and nematode infected root. Significant increase of PgChi-1 was noticed in pathogen infected roots than healthy roots. This study revealed that PgChi-1 may protect the P. ginseng under both biotic and abiotic stress conditions. PMID- 20306228 TI - Competence of an artificial bent DNA as a transcriptional activator in mouse ES cells. AB - Curved DNA structures with a left-handed superhelical conformation can activate eukaryotic transcription. However, their potency in transgene activation in embryonic stem (ES) cells has not been examined. T20 is an artificial curved DNA of 180 bp that serves as a transcriptional activator. We investigated the effect of T20 on transcription in mouse ES cell lines or hepatocytes differentiated from them. We established 10 sets of cell lines each harboring a single copy of the reporter construct. Each set comprised a T20-harboring cell line and a T20-less control cell line. Analyses showed that in ES cells and in hepatocytes originating from these cells, T20 both activated and repressed transcription in a manner that was dependent on the locus of reporter. The present and previous studies strongly suggest that in cells that have a strict gene regulation system, transcriptional activation by T20 occurs only in a transcriptionally active locus in the genome. PMID- 20306229 TI - The 5178C/A and 16189T/C polymorphisms of mitochondrial DNA in Korean men and their associations with blood iron metabolism. AB - Several studies reported that there were the associations between the genetic polymorphisms in the mitochondrial DNA (mtDNA) and some blood iron markers. Thus, we tried to investigate the relationship between two genetic polymorphisms (5178C/A and 16189T/C) in the mtDNA and several blood iron markers in Korean men. A total of unrelated 131 Korean men were participated in this study. Two genetic polymorphisms in the mtDNA was determined by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) method, and hematological or biochemical assay performed by autoanalyzer. Although the 16189T/C polymorphism was not significantly associated with any iron parameters measured in this study, we found that the 5178C/A polymorphism was significantly associated with red blood cell (RBC) count and hematocrit (HCT) value in Korean men (P < 0.05). Therefore, our data suggest that the 5178C/A polymorphism in the mtDNA might be useful as a genetic marker with respect to blood iron metabolism. PMID- 20306230 TI - Phylogenetic analysis of 16S rRNA gene sequences reveals distal gut bacterial diversity in wild wolves (Canis lupus). AB - The aim of this study was to describe the microbial communities in the distal gut of wild wolves (Canis lupus). Fecal samples were collected from three healthy unrelated adult wolves captured at the nearby of Dalai Lake Nature Reserve in Inner Mongolia of China. The diversity of fecal bacteria was investigated by constructing PCR-amplified 16S rRNA gene clone libraries using the universal bacterial primers 27 F and 1493 R. A total of 307 non-chimeric near-full-length 16S rRNA gene sequences were analyzed and 65 non-redundant bacteria phylotypes (operational taxonomical units, OTUs) were identified. Seventeen OTUs (26%) showed less than 98% sequence similarity to 16S rRNA gene sequences were reported previously. Five different bacterial phyla were identified, with the majority of OTUs being classified within the phylum Firmicutes (60%), followed by Bacteroidetes (16.9%), Proteobacteria (9.2%), Fusobacteria (9.2%) and Actinobacteria (4.6%). The majority of clones fell within the order Clostridiales (53.8% of OTUs). It was predominantly affiliated with five families: Lachnospiraceae was the most diverse bacterial family in this order, followed by Ruminococcaceae, Clostridiaceae, Peptococcaceae and Peptostreptococcaceae. PMID- 20306231 TI - Analysis on DNA sequence of KiSS-1 gene and its association with litter size in goats. AB - Three pairs of primers were designed to clone the goat KiSS-1 and scan polymorphisms and four pairs to detect polymorphisms in sexual precocious and sexual late-maturing goat breeds. A 4118 bp DNA fragment was obtained, which contains an ORF of 408 bp and encodes 135 amino acids, having a high homology with other mammals. The protein was predicted containing a signal peptide of 17 amino acids. There are two mutations (G3433A [A86T] and C3688A) in exon 3, three mutations (G296C, G454T and T505A) in intron 1 and a 18 bp deletion (-)/insertion (+) (1960-1977) in intron 2 and no mutations in exon 2. The genotype distribution didn't show obvious difference between sexual precocious and sexual late-maturing goat breeds and no consistency within the sexual late-maturing breeds. For the 296 locus, the Jining Grey goats with genotype CC had 0.80 (P < 0.01) or 0.77 (P < 0.01) kids more than those with genotype GG or GC, respectively. No significant difference (P > 0.05) was found in litter size between GG and GC. For the 1960 1977 locus, the Jining Grey goat does with genotype -/- had 0.77 (P < 0.01) or 0.73 (P < 0.01) kids more than those with +/+ or +/-, respectively. No significant difference (P > 0.05) was found in litter size between +/+ and +/- genotypes. For the other four loci, no significant difference (P > 0.05) was found in litter size between different genotypes in Jining Grey goats. The present study preliminarily indicated an association between allele C of the 296 locus and allele (-) of the 1960-1977 locus in KiSS-1 and high litter size in Jining Grey goats. PMID- 20306232 TI - A method for detecting significant genomic regions associated with oral squamous cell carcinoma using aCGH. AB - Array comparative genomic hybridization (aCGH) provides a genome-wide technique for identifying chromosomal aberrations in human diseases, including cancer. Chromosomal aberrations in cancers are defined as regions that contain an increased or decreased DNA copy number, relative to normal samples. The identification of genomic regions associated with systematic aberrations provides insights into initiation and progression of cancer, and improves diagnosis, prognosis, and therapy strategies. The McNemar test can be used to detect differentially expressed genes after discretization of gene expressions in a microarray experiment for the matched dataset. In this study, we propose a method to detect significantly altered DNA regions, shifted McNemar test, which is based on the standard McNemar test and takes into account changes in copy number variations and the region size throughout the whole genome. In addition, this novel method can be used to detect genomic regions associated with the progress of oral squamous cell carcinoma (OSCC). The performance of the proposed method was evaluated based on the homogeneity within the selected regions and the classification accuracies of the selected regions. This method might be useful for identifying new candidate genes that neighbor known genes based on the whole genomic variation because it detects significant chromosomal regions, not independent probes. PMID- 20306233 TI - Determination of boron contents in water samples collected from the Neelum valley, Azad Kashmir, Pakistan. AB - Intake of boron from food and drinking water may pose a risk to the public health above a certain concentration level. Therefore, knowledge of boron concentration in drinking water and food items is essential. In this context, samples of drinking water were collected from natural springs of the Neelum valley, Azad Kashmir, hit by devastating earthquake in 2005. In these samples, boron concentration was determined using neutron-induced radiography technique. To do so, unknown water samples, along with standard of known boron dried on CR-39 detectors, were irradiated with thermal neutrons. After exposure, CR-39 detectors were etched in 6 M NaOH at 70 degrees C. The tracks produced due to the alpha particles and (7)Li ions as a result of (10)B(n,alpha)(7)Li reaction were counted under an optical microscope. The tracks produced in theses samples were then related to the boron contents. The measured boron concentration in water samples was found to vary from 0.105 +/- 0.005 to 0.247 +/- 0.013 mg/l with an average value of 0.17 +/- 0.04 mg/l, which are within the acceptable limits. PMID- 20306234 TI - Influence of methionine on toxicity of fluoride in the liver of rats. AB - Oxidative stress is a common mechanism by which chemical toxicity can occur in the liver. The aim of the studies conducted has been to determine what influence the administration of methionine during intoxication with sodium fluoride may have upon the selected enzymes of the antioxidative system in rat liver. The experiment was carried out on Wistar FL rats (adult females) that, for 35 days, were administered distilled water, NaF, or NaF with methionine (doses: 10 mg NaF/kg bw/day, 10 mg Met/kg bw/day). The influence of administered NaF and Met was examined by analyzing the activity of the antioxidative enzymes: superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, and glutathione transferase in the liver. The results suggest that fluoride reduces the efficiency of the enzymatic antioxidative system in the liver. Administration of methionine during intoxication with sodium fluoride does not have an advantageous influence upon the activity of superoxide dismutase, catalase, reductase, and glutathione transferase in the liver. The slight increase of the activity of glutathione peroxidase after administration of methionine may indicate its protective influence upon that enzyme. PMID- 20306236 TI - Efficient DNA extraction from nail clippings using the protease solution from Cucumis melo. AB - Owing to the increasing importance of genomic information, obtaining genomic DNA easily from biological specimens has become more and more important. This article proposes an efficient method for obtaining genomic DNA from nail clippings. Nail clippings can be easily obtained, are thermostable and easy to transport, and have low infectivity. The drawback of their use, however, has been the difficulty of extracting genomic material from them. We have overcome this obstacle using the protease solution obtained from Cucumis melo. The keratinolytic activity of the protease solution was 1.78-fold higher than that of proteinase K, which is commonly used to degrade keratin. With the protease solution, three times more DNA was extracted than when proteinase K was used. In order to verify the integrity of the extracted DNA, genotype analysis on 170 subjects was performed by both PCR-RFLP and Real Time PCR. The results of the genotyping showed that the extracted DNA was suitable for genotyping analysis. In conclusion, we have developed an efficient extraction method for using nail clippings as a genome source and a research tool in molecular epidemiology, medical diagnostics, and forensic science. PMID- 20306235 TI - Regulation of redox signaling by selenoproteins. AB - The unique chemistry of oxygen has been both a resource and threat for life on Earth for at least the last 2.4 billion years. Reduction of oxygen to water allows extraction of more metabolic energy from organic fuels than is possible through anaerobic glycolysis. On the other hand, partially reduced oxygen can react indiscriminately with biomolecules to cause genetic damage, disease, and even death. Organisms in all three superkingdoms of life have developed elaborate mechanisms to protect against such oxidative damage and to exploit reactive oxygen species as sensors and signals in myriad processes. The sulfur amino acids, cysteine and methionine, are the main targets of reactive oxygen species in proteins. Oxidative modifications to cysteine and methionine can have profound effects on a protein's activity, structure, stability, and subcellular localization. Non-reversible oxidative modifications (oxidative damage) may contribute to molecular, cellular, and organismal aging and serve as signals for repair, removal, or programmed cell death. Reversible oxidation events can function as transient signals of physiological status, extracellular environment, nutrient availability, metabolic state, cell cycle phase, immune function, or sensory stimuli. Because of its chemical similarity to sulfur and stronger nucleophilicity and acidity, selenium is an extremely efficient catalyst of reactions between sulfur and oxygen. Most of the biological activity of selenium is due to selenoproteins containing selenocysteine, the 21st genetically encoded protein amino acid. The most abundant selenoproteins in mammals are the glutathione peroxidases (five to six genes) that reduce hydrogen peroxide and lipid hydroperoxides at the expense of glutathione and serve to limit the strength and duration of reactive oxygen signals. Thioredoxin reductases (three genes) use nicotinamide adenine dinucleotide phosphate to reduce oxidized thioredoxin and its homologs, which regulate a plethora of redox signaling events. Methionine sulfoxide reductase B1 reduces methionine sulfoxide back to methionine using thioredoxin as a reductant. Several selenoproteins in the endoplasmic reticulum are involved in the regulation of protein disulfide formation and unfolded protein response signaling, although their precise biological activities have not been determined. The most widely distributed selenoprotein family in Nature is represented by the highly conserved thioredoxin like selenoprotein W and its homologs that have not yet been assigned specific biological functions. Recent evidence suggests selenoprotein W and the six other small thioredoxin-like mammalian selenoproteins may serve to transduce hydrogen peroxide signals into regulatory disulfide bonds in specific target proteins. PMID- 20306238 TI - Solid-state properties of the cyclooxygenase-1-selective inhibitor, SC-560. PMID- 20306237 TI - Single-batch production of recombinant human polyclonal antibodies. AB - We have previously described the development and implementation of a strategy for production of recombinant polyclonal antibodies (rpAb) in single batches employing CHO cells generated by site-specific integration, the Sympress I technology. The Sympress I technology is implemented at industrial scale, supporting a phase II clinical development program. Production of recombinant proteins by site-specific integration, which is based on incorporation of a single copy of the gene of interest, makes the Sympress I technology best suited to support niche indications. To improve titers while maintaining a cost efficient, highly reproducible single-batch manufacturing mode, we have evaluated a number of different approaches. The most successful results were obtained using random integration in a new producer cell termed ECHO, a CHO DG44 cell derivative engineered for improved productivity at Symphogen. This new expression process is termed the Sympress II technology. Here we describe proof-of-principle data demonstrating the feasibility of the Sympress II technology for single-batch rpAb manufacturing using two model systems each composed of six target-specific antibodies. The compositional stability and the batch-to-batch reproducibility of rpAb produced by the ECHO cells were at least as good as observed previously using site-specific integration technology. Furthermore, the new process had a significant titer increase. PMID- 20306239 TI - Capital budgeting decisions using the discounted cash flow method. PMID- 20306240 TI - Urgent replacement of a mechanical mitral prosthesis in an anticoagulated patient with Bombay red blood cell phenotype. AB - PURPOSE: Bombay red blood cell phenotype is an extremely rare blood type for which patients can receive only autologous or Bombay phenotype red blood cells. We report a case of urgent repeat sternotomy for replacement of a mechanical mitral prosthesis in a patient with Bombay phenotype anticoagulated with warfarin, to emphasize the transfusion challenges in such patients. CLINICAL FEATURES: A male of Indian descent presented to hospital with New York Heart Association IV symptoms. His medical history revealed previous mitral valve replacement with a mechanical prosthesis in 2005 and Bombay phenotype blood. Preoperative transthoracic echocardiography demonstrated thrombus obstruction of the mitral prosthesis despite anticoagulation with warfarin. Right ventricular systolic pressure was >100 mmHg with 3+ tricuspid regurgitation. The patient's condition was temporized with diuretics, bronchodilators, and bi-level positive airway pressure ventilation while transfusion medicine and cardiac surgery were consulted for urgent surgery. The patient received vitamin K and prothrombin complex concentrate prior to repeat sternotomy and successful mitral prosthesis replacement. After cardiopulmonary bypass, heparinization was corrected with protamine and followed by a second dose of prothrombin complex concentrate and recombinant activated factor VIIa. Postoperatively, the patient received four units of packed red blood cells, two autologous units and two units of Bombay specific red blood cells. Right ventricular pressures stabilized at 40 mmHg following surgery. The patient recovered following several days of inotropic support with milrinone, diuretics, and bronchodilators. CONCLUSION: Patients with Bombay phenotype red blood cells present as type O, but they are unable to receive red blood cells from any phenotype other than Bombay phenotype. They are able to receive all other blood products, including fresh frozen plasma, cryoprecipitate, platelets, prothrombin complex concentrate, and recombinant activated factor VIIa. Coordination between Canadian Blood Services, transfusion medicine, surgery, and anesthesia is important in managing these patients. PMID- 20306242 TI - The leukemia stem cell. PMID- 20306241 TI - [Hospital-based active surveillance of human leptospirosis in Cambodia]. AB - Leptospirosis has been so far poorly described in Cambodia and is probably underdiagnosed in the current local medical practices, although conditions to its active circulation exist in this country. Between June 2006 and July 2007, 612 patients admitted to Takeo hospital and Calmette hospital in Phnom Penh presenting clinical symptoms compatible with leptospirosis, were recruited for biological investigation of leptospirosis markers: PCR detection of bacterial DNA and serology using an Elisa-IgM test and the micro-agglutination reference test (MAT). One hundred eighty-three patients (29.9%) were found to be carrying at least one biological marker of leptospirosis, 88 (14.4%) showed an acute infection profile, evidenced by a positive PCR. The proportion of patients with an immune phase profile (15.5%) suggests former contacts with Leptospira and possible infections with little or no symptoms. Thirteen serogroups of Leptospira have been identified, with predominance of Panama, Pyrogenes and Australia, illustrating a probable wide range of animal reservoir hosts. Serogroup Icterohaemorrhagiae was found in only 4% of cases, contrasting with usual features of human leptospirosis. No significant link between infection and sex, age or occupation could be established, suggesting a permanent exposure of the population in its daily life rather than the existence of risk groups. This study, the largest conducted to date on leptospirosis in Cambodia, confirms the importance of this zoonotic disease, that must be considered a real public health issue in this country. PMID- 20306243 TI - Epigenetic mechanisms in AML - a target for therapy. AB - Epigenetics refers to a stable, mitotically perpetuated regulatory mechanism of gene expression without an alteration of the coding sequence. Epigenetic mechanism include DNA methylation and histone tail modifications. Epigenetic regulation is part of physiologic development and becomes abnormal in neoplasia, where silencing of critical genes by DNA methylation or histone deacetylation can contribute to leukemogenesis as an alternative to deletion or loss-of-function mutation. In acute myelogenous leukemia (AML), aberrant DNA methylation can be observed in multiple functionally relevant genes such as p15, p 73, E-cadherin, ID 4, RARbeta2. Abnormal activities of histone tail-modifying enzymes have also been seen in AML, frequently as a direct result of chromosomal translocations. It is now clear that these epigenetic changes play a significant role in development and progression of AML, and thus constitute important targets of therapy. The aim of targeting epigenetic effector protein or "epigenetic therapy" is to reverse epigenetic silencing and reactive various genes to induce a therapeutic effect such as differentiation, growth arrest, or apoptosis. Recent clinical studies have shown the relative safety and efficacy of such epigenetic therapies. PMID- 20306244 TI - Chromosomal translocations in AML: detection and prognostic significance. PMID- 20306245 TI - Chromosomal deletions in AML. AB - Several, acquired, non-random chromosomal deletions have been characterized in acute myelogenous leukemia (AML). While the deletion limits vary among patients, there are consistent regions of overlap among the deleted segments between patients. Furthermore, chromosomal deletions are achieved frequently by unbalanced translocations between two and more chromosomes resulting loss of candidate leukemia suppressor loci from the affected chromosomes. Most deletions occurring as sole anomalies are associated with good-intermediate clinical outcome, but complex cytogenetic anomalies signify an aggressive clinical course. Thanks to the exciting development in microarray, siRNA technologies, a number of candidate AML suppressor genes localizing to the critical regions of overlap within the deletions have been identified recently. Most of the candidate genes do not function by the classical "two hits," namely loss of an allele unmasking inactivating mutations in the remaining allele. Gene dosage, epigenetic silencing, and uniparental disomy appear to be common mechanisms of gene inactivation in AML. While several of the newly discovered candidate genes lead to new pathways, a few of them affect previously known leukemogenic targets. Thus the investments made over the years on leukemia suppressor gene discovery are beginning to yield reasonable results at the present time. Future beholds promise for targeted therapy of these poorly characterized AMLs, as we uncover the mutations driving their clonal evolution. PMID- 20306246 TI - Genes predictive of outcome and novel molecular classification schemes in adult acute myeloid leukemia. AB - The pretreatment karyotype of leukemic blasts is currently the key determinant in therapy decision making in acute myeloid leukemia (AML). The World Health Organization (WHO) has recognized this important information by including, besides clinical, cytological, cytochemical, and immunophenotypical features, recurrent cytogenetic abnormalities in its classification (Table 1). However, although the WHO defines important biologically and clinically relevant entities, the prognostic value of some of the well-defined cytogenetic subgroups is partially masked in the WHO classification. Moreover, in the recent past a number of novel molecular aberrations with marked prognostic value, which are not yet incorporated in the WHO classifications have been identified. These molecular abnormalities include mutations (e.g., in FLT3, c-KIT, and NPM1), partial duplications (e.g., of MLL and FLT3), and abnormal expression of pathogenetic genes (e.g., EVI1, WT1, BCL2, MDR1, BAALC, and ERG). In addition, novel molecular approaches in genomics, like monitoring the expression levels of thousands of genes in parallel using DNA microarray technology, open possibilities for further refinement of prognostication of AML. Gene expression profiling in AML is already well established and has proven to be valuable to recognize various cytogenetic subtypes, discover novel AML subclasses, and predict clinical outcome. The current advances made in molecular understanding of AML will ultimately lead to a further refinement of prognostics of AML. PMID- 20306247 TI - Receptor tyrosine kinase alterations in AML - biology and therapy. AB - Acute myeloid leukemia (AML) is the most common form of leukemia in adults, and despite some recent progress in understanding the biology of the disease, AML remains the leading cause of leukemia-related deaths in adults and children. AML is a complex and heterogeneous disease, often involving multiple genetic defects that promote leukemic transformation and drug resistance. The cooperativity model suggests that an initial genetic event leads to maturational arrest in a myeloid progenitor cell, and subsequent genetic events induce proliferation and block apoptosis. Together, these genetic abnormalities lead to clonal expansion and frank leukemia. The purpose of this chapter is to review the biology of receptor tyrosine kinases (RTKs) in AML, exploring how RTKs are being used as novel prognostic factors and potential therapeutic targets. PMID- 20306248 TI - Lineage-specific transcription factor aberrations in AML. AB - Transcription factors play a key role in the commitment of hematopoietic stem cells to differentiate into specific lineages [78]. This is particularly important in that a block in terminal differentiation is the key contributing factor in acute leukemias. This general theme of the role of transcription factors in differentiation may also extend to other tissues, both in terms of normal development and cancer. Consistent with the role of transcription factors in hematopoietic lineage commitment is the frequent finding of aberrations in transcription factors in AML patients. Here, we intend to review recent findings on aberrations in lineage-restricted transcription factors as observed in patients with acute myeloid leukemia (AML). PMID- 20306249 TI - Proleukemic RUNX1 and CBFbeta mutations in the pathogenesis of acute leukemia. AB - The existence of non-random mutations in critical regulators of cell growth and differentiation is a recurring theme in cancer pathogenesis and provides the basis for our modern, molecular approach to the study and treatment of malignant diseases. Nowhere is this more true than in the study of leukemogenesis, where research has converged upon a critical group of genes involved in hematopoietic stem and progenitor cell self-renewal and fate specification. Prominent among these is the heterodimeric transcriptional regulator, RUNX1/CBFbeta. RUNX1 is a site-specific DNA-binding protein whose consensus response element is found in the promoters of many hematopoietically relevant genes. CBFbeta interacts with RUNX1, stabilizing its interaction with DNA to promote the actions of RUNX1/CBFbeta in transcriptional control. Both the RUNX1 and the CBFbeta genes participate in proleukemic chromosomal alterations. Together they contribute to approximately one-third of acute myelogenous leukemia (AML) and one-quarter of acute lymphoblastic leukemia (ALL) cases, making RUNX1 and CBFbeta the most frequently affected genes known in the pathogenesis of acute leukemia. Investigating the mechanisms by which RUNX1, CBFbeta, and their proleukemic fusion proteins influence leukemogenesis has contributed greatly to our understanding of both normal and malignant hematopoiesis. Here we present an overview of the structural features of RUNX1/CBFbeta and their derivatives, their roles in transcriptional control, and their contributions to normal and malignant hematopoiesis. PMID- 20306250 TI - Acute myeloid leukemia with mutated nucleophosmin (NPM1): molecular, pathological, and clinical features. AB - The NPM1 gene encodes for nucleophosmin, a nucleolus-located shuttling protein that is involved in multiple cell functions, including regulation of ribosome biogenesis, control of centrosome duplication and preservation of ARF tumor suppressor integrity. The NPM1 gene is specifically mutated in about 30% acute myeloid leukemia (AML) but not in other human neoplasms. Mutations cause crucial changes at the C-terminus of the NPM1 protein that are responsible for the aberrant nuclear export and accumulation of NPM1 mutants in the cytoplasm of leukemic cells. Diagnosis of AML with mutated NPM1 can be done using molecular techniques, immunohistochemistry (looking at cytoplasmic dislocation of nucleophosmin that is predictive of NPM1 mutations) and Western blotting with antibodies specifically directed against NPM1 mutants. Because of its distinctive molecular, pathological, immunophenotypic and prognostic features, AML with mutated NPM1 (synonym: NPMc+ AML) has been included, as a new provisional entity, in the 2008 World Health Organization (WHO) classification of myeloid neoplasms. PMID- 20306251 TI - MicroRNAs: new players in AML pathogenesis. PMID- 20306252 TI - Murine models of human acute myeloid leukemia. AB - Primary human AML cells can be isolated and studied in vitro, but many experimental questions can only be addressed using in vivo models. In particular, tractable animal models are needed to test novel therapies. The genetic complexity of human AML poses significant challenges for the generation of reliable animal models. The hematopoietic systems of both zebrafish ( Danio rerio) and Drosophila have been well characterized ( reviewed in [5, 31]) . Both organisms are well suited to forward genetics mutagenesis screens. Although this approach has been useful for identification of mutants with hematopoietic phenotypes ( e.g., cloche), the impact on cancer biology and hematopoietic malignancies in particular has been limited. A zebrafish model of acute lymphoblastic leukemia has been generated [37] and Drosophila models have shed light on the biology of epithelial tumors ( reviewed in [60]). Nonetheless, in vivo modeling of human AML relies most heavily on mice. Most cellular, molecular, and developmental features of the hematopoietic system are well conserved across mammalian species. The availability of the human and mouse genome sequences and the capability of manipulating the mouse genome make mice the most valuable model organism for AML research. Mice have additional practical value because they have a short reproductive cycle and are relatively inexpensive to house. PMID- 20306254 TI - Acute promyelocytic leukemia: a paradigm for differentiation therapy. AB - Acute promyelocytic leukemia(APL) is characterized by the t(15;17) chromosomal translocation leading to the formation of the PML-RARalpha oncoprotein. This leukemia has attracted considerable interest in recent years, being the first in which therapies that specifically target the underlying molecular lesion, i.e., all-trans retinoic acid (ATRA) and arsenic trioxide (ATO), leading to induction of differentiation and apoptosis have been successfully used in clinical practice. The advent of ATRA therapy has transformed APL from being a disease with a poor outlook to one of the most prognostically favorable subsets of acute myeloid leukemia. Further improvements in outcome may be achieved with the use of ATO, which achieves high rates of remission in the relatively small proportion of patients now relapsing following standard first-line therapy with ATRA and anthracycline-based chemotherapy. Moreover, recent studies have suggested that ATO and ATRA, or even ATO alone, used as front-line treatment of PML-RARA- associated APL can induce long-term remissions. This raises the possibility that some patients can be cured using differentiation therapies alone, without the need for chemotherapy, thereby potentially reducing treatment-related toxicity. It is clear that the success of such an approach is critically dependent upon molecular diagnostics and monitoring for minimal residual disease (MRD) to distinguish those patients who can potentially be cured with differentiation therapy from those requiring additional myelosuppressive agents. This represents an exciting new phase in the treatment of acute leukemia, highlighting the potential of molecularly targeted and MRD-directed therapies to achieve an individualized approach to patient management. PMID- 20306255 TI - Immunotherapy of AML. AB - The applications of chemotherapy for the treatment of AML have been unchanged over the past three decades, with only 30% of patients demonstrating disease-free survival (DFS) [118]. Despite achieving CR following induction chemotherapy, the majority of patients relapse and succumb to their disease [6]. In view of the limitations encountered by cytarabine/anthracycline based regimes, attention has shifted to immunotherapy as a means to treat AML and provide significant long term DFS. This chapter will discuss the role of the immune system and recent advances in immunotherapy for the treatment of AML, focusing on cellular and non cellular approaches. PMID- 20306253 TI - Apoptosis in leukemias: regulation and therapeutic targeting. AB - Nearly 25 years after the seminal publication of John Foxton Kerr that first described apoptosis, the process of regulated cell death, our understanding of this basic physiological phenomenon is far from complete [39]. From cardiovascular disease to cancer, apoptosis has assumed a central role with broad ranging therapeutic implications that depend on a complete understanding of this process, yet have also identified an incredibly complex regulatory system that is critical for development and is at the core of many diseases, challenging scientist and clinicians to step into its molecular realm and modulate its circuitry for therapeutic purposes. This chapter will review our understanding of the molecular circuitry that controls apoptosis in leukemia and the pharmacological manipulations of this pathway that may yield therapeutic benefit. PMID- 20306256 TI - Therapy of acute myelogenous leukemia in adults. PMID- 20306258 TI - Evaluation of the effects and mechanisms of action of glufosinate, an organophosphate insecticide, on striatal dopamine release by using in vivo microdialysis in freely moving rats. AB - The purpose of the present work was to assess the effects of glufosinate ammonium (GLA), an aminoacid structurally related to glutamate, on in vivo dopamine (DA) release from rat striatum, using brain microdialysis coupled to HPLC-EC. Intrastriatal administration of GLA produced significant concentration-dependent increases in DA levels. At least two mechanisms can be proposed to explain these increases: GLA could be inducing DA release from synaptic vesicles or producing an inhibition of DA transporter (DAT). Thus, we investigated the effects of GLA under Ca(++)-free condition, and after pretreatment with reserpine and TTX. It was observed that the pretreatment with Ca(++)-free Ringer, reserpine or TTX significantly reduced the DA release induced by GLA. Coinfusion of GLA and nomifensine shows that the GLA-induced DA release did not involve the DAT. These results show that GLA-induced striatal DA release is probably mediated by an exocytotic-, Ca(++)-, action potential-dependent mechanism, being independent of DAT. PMID- 20306257 TI - Regulation of tumor suppressor p53 at the RNA level. AB - p53 is a key tumor suppressor that triggers cell cycle arrest, senescence, or apoptosis in response to cellular stress. Frequent p53 mutation in human tumors allows survival, sustained growth, and tumor progression. p53 is expressed at low levels under normal conditions, due to rapid protein turnover. Stress signaling induces p53 protein stabilization through phosphorylation and other post translational modifications. However, recent studies have demonstrated critical regulation of p53 at the mRNA level, mediated via both the 5'UTR and the 3'UTR and affecting both the stability and the translation efficiency of the p53 mRNA. Both proteins and microRNAs have been implicated in such regulation. The p53 target gene Wig-1 encodes a zinc finger protein that binds to double-stranded RNA and enhances p53 mRNA stability by binding to the 3'UTR in a positive feedback loop. Here, we shall summarize current knowledge about regulation of the p53 mRNA and discuss possible implications for cancer therapy. PMID- 20306259 TI - LC-QqLIT MS analysis of nine sulfonamides and one of their acetylated metabolites in the Llobregat River basin. Quantitative determination and qualitative evaluation by IDA experiments. AB - Robust instrumental analytical chemistry and the subsequent development of improved analytical methodologies and extraction procedures have enabled the detection at environmental levels of new emerging contaminants, for example pharmaceuticals. The objective of this study was to explore the potential of liquid chromatography-tandem quadrupole-linear ion trap (LC-QqLIT MS) for quantitative determination of nine sulfonamides (SAs) and one acetylated metabolite in surface water from the Llobregat River and one of its main tributaries, the Anoia River, in Catalonia (Spain). A total of 21 samples were taken in three sampling campaigns. Recoveries ranging from 26% to 123% were calculated for the SAs studied, and method limits of detection (MLODs) achieved were in the range 0.05-0.2 ng L(-1). Through the different campaigns, concentrations ranged from 0.74 ng L(-1) (sulfamethizole) to 2,482 ng L(-1) (sulfamethazine) in the Llobregat River, and from 0.27 ng L(-1) (sulfamethizole) to 168 ng L(-1) (sulfamethoxazole) in the Anoia River. Sulfamethoxazole and sulfapyridine were the two SAs most frequently detected (80% and 71% respectively). N(4)-acetylsulfamethazine was detected in both rivers, but with different frequencies (4% of the samples from the Anoia River and 43% of those from the Llobregat River). Information-dependent acquisition (IDA) experiments were also developed in order to obtain enhanced product-ion spectra in surface water samples. PMID- 20306261 TI - Efficiency of iloprost treatment for osseous malperfusion. AB - Insufficient osseous blood supply results in bone marrow oedema (BMO) and/or avascular necrosis (AVN). One treatment option to support osseous perfusion is the application of stable prostacycline analog iloprost. In this clinical study, 95 patients were treated with iloprost for BMO/AVN. One hundred eighty-six bones were affected by BMO/AVN before treatment. Average follow-up was 33.0 +/- 17.6 months. Pain levels could be reduced (e.g. visual analogue scale, 5.0 +/- 2.2 points reduced to 1.7 +/- 2.2 points) and functional scores improved (Harris hip score, 52 +/- 21 points to 79 +/- 17 points) in the course of treatment. According to current data, healing of advanced stages of osteonecrosis is not possible. However, the results of this case series confirm previous findings that in early stages of insufficient osseous blood flow iloprost can contribute to the relief of pain and improve joint function. PMID- 20306262 TI - Reliable techniques to avoid damaging the superficial radial nerve due to percutaneous Kirschner wire fixation of the distal radius fracture through the radial styloid process. AB - PURPOSE: The use of percutaneous Kirschner wires for fixation of unstable fractures of the distal radius has been widely accepted as the least invasive procedure. However, the injury to the superficial branch of the radial nerve (SBRN) is common. Our purpose in this study was to develop a reliable technique to avoid damaging the SBRN. METHODS: Twenty cadaver forearms were dissected to identify the SBRN distribution, and 18 forearms were used to undergo placement of three Kirschner wires (KW-A, KW-B, and KW-C). The KW-A, KW-B, and KW-C were driven in the frontal plane into the distal radius, and KW-A and KW-C through the tip of radial styloid process at different angles. The SBRN distribution and its relationship with the KW insertion were identified. Fifty-three patients with unstable distal radius fractures were fixed with external fixator and augmented with 1-3 KW, and the injury rates of SBRN were evaluated. RESULTS: We found a blind region of the SBRN bound by its first bifurcations into radial and ulnar branches and the line crossing the tip of the styloid process. The mean distance of the three wires (KW-A, KW-C, and KW-B) to the closest nerve branch was 4.5, 4.4, and 3.4 mm, respectively. The injury of SBRN occurred in two of 53 patients. CONCLUSION: The injury rate of the SBRN can be effectively reduced when the Kirschner wire is placed along the curve AB and as in proximity to the TRSP as possible under fluoroscopic guidance. Our pinning technique is therefore reliable and practical. PMID- 20306263 TI - Ultrasound-guided intratumoral administration of collagenase-2 improved liposome drug accumulation in solid tumor xenografts. AB - PURPOSE: To investigate the effect of intratumoral administration of collagenase 2 on liposomal drug accumulation and diffusion in solid tumor xenografts. METHODS: Correlation between tumor interstitial fluid pressure (IFP) and tumor physiological properties (size and vessel fraction by B-mode and Doppler ultrasound, respectively) was determined. IFP response to intravenous or intratumoral collagenase-2 (0.1%) treatment was compared with intratumoral deactivated collagenase-2. To evaluate drug accumulation and diffusion, technetium-99 m-((99m)Tc)-liposomal doxorubicin (Doxil) was intravenously injected after collagenase-2 (0.1 and 0.5%, respectively) treatment, and planar scintigraphic images acquired and percentage of the injected dose per gram tissue calculated. Subsequently, tumors were subjected to autoradiography and histopathology. RESULTS: IFP in two-week-old head and neck squamous cell carcinoma xenografts was 18 +/- 3.7 mmHg and not correlated to the tumor size but had reverse correlation with the vessel fraction (r = -0.91, P < 0.01). Intravenous and intratumoral collagenase-2 use reduced IFP by a maximum of 35 40%. Compared to the control, the low IFP level achieved through intratumoral route remained for a long period (24 vs. 2 h, P < 0.05). SPECT images and autoradiography showed significantly higher (99m)Tc-Doxil accumulation in tumors with intratumoral collagenase-2 treatment, confirmed by %ID/g in tumors (P < 0.05), and pathological findings showed extensive distribution of Doxil in tumors. CONCLUSIONS: Intratumoral injection of collagenase-2 could effectively reduce IFP in HNSCC xenografts for a longer period than using intravenous approach, which allowed for more efficient accumulation and homogeneous diffusion of the Doxil within the tumor interstitium. PMID- 20306264 TI - Oral bioavailability of DN101, a concentrated formulation of calcitriol, in tumor bearing dogs. AB - PURPOSE: High-dose calcitriol (1,25-dihydroxyvitamin D(3)) has antineoplastic activity against a range of tumors and potentiates chemotherapeutic agents. In an earlier canine study, the MTD of intravenous (i.v.) calcitriol was 3.75 MUg/kg, but polysorbate-associated hypersensitivity reactions were common. Use of commercially available oral calcitriol is limited by the absence of a formulation of suitable strength to allow administration of a reasonable number of caplets. This study evaluated the bioavailability of DN101, a concentrated oral calcitriol formulation specifically developed for anticancer applications. METHODS: An open label, single-dose, 2-way crossover study was conducted. Dogs randomly received a single 3.75 MUg/kg dose of calcitriol either i.v. or oral (as DN101), followed by cisplatin (60 mg/m(2)). Three weeks later, the alternate form of calcitriol was given prior to another dose of cisplatin. Dogs received antihistamines and corticosteroids prior to both treatments. Food was withheld for 12 h before and after therapy. Serum calcitriol concentrations were measured by radioimmunoassay. RESULTS: Ten tumor-bearing dogs received both i.v. and oral calcitriol. Six dogs experienced hypersensitivity reactions during i.v. calcitriol. Sequence of calcitriol administration (day-1 vs. day-21) by either i.v. or oral routes had no effect on the major calcitriol pharmacokinetic parameters. Oral calcitriol resulted in significantly lower values for AUC (P = 0.05) and prolonged T (1/2) (P = 0.003) when compared to i.v. Calcitriol oral bioavailability was highly variable among dogs (mean +/- SEM, 71 +/- 12.6%). CONCLUSIONS: This study demonstrates that a high-dose formulation of calcitriol has a moderate bioavailability in dogs, but inter-individual variability in PK parameters is similar to that observed in people. With this bioavailability, serum concentrations of calcitriol that exhibit antitumor activity in a preclinical murine model were achieved in some dogs. Exploration of methods to minimize variation in calcitriol systemic exposure is warranted. PMID- 20306265 TI - Deletion of PaAif2 and PaAmid2, two genes encoding mitochondrial AIF-like oxidoreductases of Podospora anserina, leads to increased stress tolerance and lifespan extension. AB - Wild-type strains of the ascomycete Podospora anserina are characterized by a limited lifespan. Mitochondria play a central role in this ageing process raising the question of whether apoptosis-like processes, which are also connected to mitochondrial function, are involved in the control of the final stage in the fungal life cycle. While a role of two metacaspases in apoptosis and lifespan control was recently demonstrated in P. anserina, virtually nothing is known about the function of the protein family of apoptosis-inducing factors (AIFs). Here we report data about proteins belonging to this family. We demonstrate that the cytosolic members PaAIF1 and PaAMID1 do not affect lifespan. In contrast, loss of PaAIF2 and PaAMID2, which both were localized to mitochondria, are characterized by a significantly increased ROS tolerance and a prolonged lifespan. In addition, deletion of PaAmid2 severely affects sporogenesis. These data identify components of a caspase-independent molecular pathway to be involved in developmental processes and in the induction of programmed cell death in the senescent stage of P. anserina. PMID- 20306266 TI - Hormone profile in juvenile systemic lupus erythematosus with previous or current amenorrhea. AB - To identify the underlying mechanism of amenorrhea in juvenile systemic lupus erythematosus (JSLE) patients, thirty-five (11.7%) JSLE patients with current or previous amenorrhea were consecutively selected among the 298 post-menarche patients followed in 12 Brazilian pediatric rheumatology centers. Pituitary gonadotrophins [follicle-stimulating hormone (FSH) and luteinizing hormone (LH)] and estradiol were evaluated in 32/35 patients, and prolactin and total testosterone in 29/35 patients. Patient's medical records were carefully reviewed according to demographic, clinical and therapeutic findings. The mean duration of amenorrhea was 7.2 +/- 3.6 months. Low FSH or LH was observed in 7/32 (22%) JSLE patients and normal FSH or LH in 25 (78%). Remarkably, low levels of FSH or LH were associated with higher frequency of current amenorrhea (57% vs. 0%, P = 0.001), higher median disease activity (SLEDAI) and damage (SLICC/ACR-DI) (18 vs. 4, P = 0.011; 2 vs. 0, P = 0.037, respectively) and higher median current dose of prednisone (60 vs. 10 mg/day, P = 0.0001) compared to normal FSH or LH JSLE patients. None of them had decreased ovarian reserve and premature ovarian failure. Six of 29 (21%) patients had high levels of prolactin, and none had current amenorrhea. No correlations were observed between levels of prolactin and SLEDAI, and levels of prolactin and SLICC/ACR-DI scores (Spearman's coefficient). We have identified that amenorrhea in JSLE is associated with high dose of corticosteroids indicated for active disease due to hypothalamic-pituitary-ovary axis suppression. PMID- 20306267 TI - Ruptured pulmonary artery caused by isolated pulmonary valve endocarditis: case report. PMID- 20306268 TI - Abnormal tau phosphorylation in primary progressive multiple sclerosis. AB - Although neurodegeneration is the pathological substrate of progression in multiple sclerosis (MS), the underlying mechanisms remain unresolved. Abnormal phosphorylation of tau, implicated in the aetiopathogenesis of a number of classic neurodegenerative disorders, has also recently been described in secondary progressive MS (SPMS). In contrast to SPMS, primary progressive MS (PPMS) represents a significant subset of patients with accumulating neurological disability from onset. The neuropathological relationship between SPMS and PPMS is unknown. Against this background, we investigated tau phosphorylation status in five cases of PPMS using immunohistochemical and biochemical methods. We report widespread abnormal tau hyperphosphorylation of the classic tau phospho epitopes occurring in multiple cell types but with a clear immunohistochemical glial bias. In addition, biochemical analysis revealed abnormally phosphorylated insoluble tau in all cases. These findings establish a platform for further study of the role of insoluble tau formation, including determining the relevance of glial tau pathology, in the neurodegenerative phase of MS. PMID- 20306269 TI - Multi-organ distribution of phosphorylated alpha-synuclein histopathology in subjects with Lewy body disorders. AB - A sensitive immunohistochemical method for phosphorylated alpha-synuclein was used to stain sets of sections of spinal cord and tissue from 41 different sites in the bodies of 92 subjects, including 23 normal elderly, 7 with incidental Lewy body disease (ILBD), 17 with Parkinson's disease (PD), 9 with dementia with Lewy bodies (DLB), 19 with Alzheimer's disease with Lewy bodies (ADLB) and 17 with Alzheimer's disease with no Lewy bodies (ADNLB). The relative densities and frequencies of occurrence of phosphorylated alpha-synuclein histopathology (PASH) were tabulated and correlated with diagnostic category. The greatest densities and frequencies of PASH occurred in the spinal cord, followed by the paraspinal sympathetic ganglia, the vagus nerve, the gastrointestinal tract and endocrine organs. The frequency of PASH within other organs and tissue types was much lower. Spinal cord and peripheral PASH was most common in subjects with PD and DLB, where it appears likely that it is universally widespread. Subjects with ILBD had lesser densities of PASH within all regions, but had frequent involvement of the spinal cord and paraspinal sympathetic ganglia, with less frequent involvement of end-organs. Subjects with ADLB had infrequent involvement of the spinal cord and paraspinal sympathetic ganglia with rare involvement of end-organs. Within the gastrointestinal tract, there was a rostrocaudal gradient of decreasing PASH frequency and density, with the lower esophagus and submandibular gland having the greatest involvement and the colon and rectum the lowest. PMID- 20306270 TI - Resistance training induces supraspinal adaptations: evidence from movement related cortical potentials. AB - Early effects of a resistance training program include neural adaptations at multiple levels of the neuraxis, but direct evidence of central changes is lacking. Plasticity exhibited by multiple supraspinal centers following training may alter slow negative electroencephalographic activity, referred to as movement related cortical potentials (MRCP). The purpose of this study was to determine whether MRCPs are altered in response to resistance training. Eleven healthy participants (24.6 +/- 3.5 years) performed 3 weeks of explosive unilateral leg extensor resistance training. MRCP were assessed during 60 self-paced leg extensions against a constant nominal load before and after training. Resistance training was effective (P < 0.001) in increasing leg extensor peak force (+22%), rate of force production (+32%) as well as muscle activity (iEMG; +47%, P < 0.05). These changes were accompanied by several MRCP effects. Following training, MRCP amplitude was attenuated at several scalp sites overlying motor related cortical areas (P < 0.05), and the onset of MRCP at the vertex was 28% (561 ms) earlier. In conclusion, the 3-week training protocol in the present study elicited significant strength gains which were accompanied by neural adaptations at the level of the cortex. We interpret our findings of attenuated cortical demand for submaximal voluntary movement as evidence for enhanced neural economy as a result of resistance training. PMID- 20306271 TI - Kir 2.1 channelopathies: the Andersen-Tawil syndrome. AB - As a multisystem disorder, Andersen-Tawil syndrome (ATS) is rather unique in the family of channelopathies. The full spectrum of the disease is characterized by ventricular arrhythmias, dysmorphic features, and periodic paralysis. Most ATS patients have a mutation in the ion channel gene, KCNJ2, which encodes the inward rectifier K+ channel Kir2.1, a component of the inward rectifier IK1.IK1 provides repolarizing current during the most terminal phase of repolarization and is the primary conductance controlling the diastolic membrane potential. Thus, ATS is a disorder of cardiac repolarization. The chapter will discuss the most recent data concerning the genetic, cellular, and clinical data underlying this unique disorder. PMID- 20306273 TI - Anti-mitogenic and apoptotic effects of 5-HT1B receptor antagonist on HT29 colorectal cancer cell line. AB - PURPOSE: There is lack of evidence about impact of 5-HT receptors on colorectal cancers. The current study was designed to investigate the role of serotonin and its receptors in colorectal cancer cell line and tissues. METHODS: In cell cultures, we investigated the effects of 5-HT and 5-HT(1A,1B,1D) agonists and antagonists on proliferation of HT29 cells. We also tested apoptosis for the receptor antagonists. The expression of 5-HT1(A,B,D) receptor subtypes was examined by immunohistochemistry and western blotting. RESULTS: Our data indicated that 5-HT(1B) receptor was fully expressed in HT29 cell line and tumor tissues. MTT proliferation assay also revealed that serotonin and CP93129 dihydrochloride, a selective 5-HT(1B) receptor agonist, stimulated growth of HT29 cells. Further, SB224289 hydrochloride (that is a selective 5-HT(1B) receptor antagonist) had anti-proliferative and apoptotic effects on HT29 cells. CONCLUSIONS: The findings of this study provide evidence for the potential role of 5-HT(1B) receptor in colorectal cancer. Further investigation is required to explore the effect of receptor antagonists on the prevention, prognosis and treatment of patients with colorectal cancer. PMID- 20306274 TI - Patients' experience of oxygen therapy and dyspnea: a qualitative study in home palliative care. AB - BACKGROUND: Dyspnea is a common and distressing symptom in advanced cancer patients. Our preliminary work shows that in the home palliative care population sampled for this study, the prevalence of dyspnea is 29.5% and of those, 26.2% used oxygen therapy. Previous studies suggested that oxygen therapy can be a burden to patients. PURPOSE: This study seeks to report the prevalence and describe the experience of dyspnea, pattern of oxygen use, and patients' perceived benefits and/or burdens of oxygen therapy in home palliative care patients receiving oxygen therapy. METHODS: Qualitative in-depth interviews, using an interview guide, were conducted with eight participants in their homes. Thematic analysis was performed using a framework approach. RESULTS: All patients in this project used oxygen most of the time. The descriptions of shortness of breath varied and were nonspecific. The patients identified more advantages than disadvantages. The advantages of oxygen use included increased functional capacity, patients' perceiving oxygen as a life-saving intervention, as well as a symptom-management tool. The identified disadvantages were decreased mobility, discomfort related to the nasal prongs, barriers to accessing oxygen therapy and noise related to the equipment. CONCLUSION: The advantages of oxygen usage outweighed the disadvantages for this sample of patients in the home palliative setting. PMID- 20306272 TI - Nitric oxide and oxidative stress in vascular disease. AB - Endothelium-derived nitric oxide (NO) is a paracrine factor that controls vascular tone, inhibits platelet function, prevents adhesion of leukocytes, and reduces proliferation of the intima. An enhanced inactivation and/or reduced synthesis of NO is seen in conjunction with risk factors for cardiovascular disease. This condition, referred to as endothelial dysfunction, can promote vasospasm, thrombosis, vascular inflammation, and proliferation of vascular smooth muscle cells. Vascular oxidative stress with an increased production of reactive oxygen species (ROS) contributes to mechanisms of vascular dysfunction. Oxidative stress is mainly caused by an imbalance between the activity of endogenous pro-oxidative enzymes (such as NADPH oxidase, xanthine oxidase, or the mitochondrial respiratory chain) and anti-oxidative enzymes (such as superoxide dismutase, glutathione peroxidase, heme oxygenase, thioredoxin peroxidase/peroxiredoxin, catalase, and paraoxonase) in favor of the former. Also, small molecular weight antioxidants may play a role in the defense against oxidative stress. Increased ROS concentrations reduce the amount of bioactive NO by chemical inactivation to form toxic peroxynitrite. Peroxynitrite-in turn-can "uncouple" endothelial NO synthase to become a dysfunctional superoxide generating enzyme that contributes to vascular oxidative stress. Oxidative stress and endothelial dysfunction can promote atherogenesis. Therapeutically, drugs in clinical use such as ACE inhibitors, AT(1) receptor blockers, and statins have pleiotropic actions that can improve endothelial function. Also, dietary polyphenolic antioxidants can reduce oxidative stress, whereas clinical trials with antioxidant vitamins C and E failed to show an improved cardiovascular outcome. PMID- 20306275 TI - Global meaning and meaning-related life attitudes: exploring their role in predicting depression, anxiety, and demoralization in cancer patients. AB - GOAL OF WORK: While significance of the concept of meaning in understanding adaptation to cancer is widely accepted, it has been little studied, especially in longitudinal data. This study aims to clarify the role of global meaning and meaning-related life attitudes (death acceptance and goal seeking) in predicting different aspects of psychological and existential distress by reference to a specified research model. PATIENTS AND METHODS: At baseline (T1), a sample of 270 cancer patients was recruited. Data from 178 patients could be obtained after 3 months at T2. Patients completed the Life-Attitude-Profile-Revised assessing global meaning and meaning-related life attitudes, the Hospital Anxiety and Depression Scale, and the Demoralization Scale. Hierarchical regression analyses were carried out in two steps. Sociodemographic and physical factors were controlled. RESULTS: Global meaning emerged as a significant negative predictor of depression (beta = -0.27) (p <= 0.001) and demoralization (beta = -0.27) (p <= 0.001). Death acceptance was a predictor of anxiety only (beta = -0.21) (p <= 0.003), whereas goal seeking was a positive predictor of depression (beta = 0.29) (p <= 0.001), anxiety (beta = 0.36) (p <= 0.001), and demoralization (beta = 0.35) (p <= 0.001). DISCUSSION: Findings confirm a global sense of meaning as an important protecting factor regarding the development of distress symptoms. Results suggest that different dimensions of meaning contribute to different dimensions of psychological well-being, as they refer to different existential problems. The need for and relevance of meaning-focused interventions in cancer patients is strengthened. PMID- 20306276 TI - Molecular and genetic characteristics of hemagglutinin and neuraminidase in Iranian 2009 pandemic influenza A(H1N1) viruses. AB - Influenza virus infections cause severe illness worldwide. Vaccination reduces the morbidity and mortality of influenza. The efficacy of vaccines varies due to antigenic differences between the circulating influenza strains and the vaccine. Neuraminidase inhibitors are effective for prophylaxis and treatment of influenza infections, and the emergence of drug resistant mutants is an important challenge. Full-length nucleotide and deduced amino acid sequences of the hemagglutinin and neuraminidase genes of three 2009 pandemic influenza A/H1N1 isolates were compared with the vaccine strain and some strains from different countries. Phylogenetic analysis for hemagglutinin and neuraminidase showed they were related to their vaccine strain, with an average of 99.56 and 99.53% sequence identity, respectively. No genetic indication of resistance to neuraminidase inhibitors was found. Although genomic analysis of hemagglutinin and neuraminidase genes of Iranian strains in comparison to the corresponding vaccine strain revealed some mutations, none of these were identified in functionally important receptor-binding sites. PMID- 20306277 TI - 3D-QSAR studies on caspase-mediated apoptosis activity of phenolic analogues. AB - Phenols and its analogues are known to induce caspase-mediated apoptosis activity and cytotoxicity on various cancer cell lines. In the current work, two types of molecular field analysis techniques were used to perform the three dimension quantitative structure activity relationship (3D-QSAR) modeling between structural characters and anticancer activity of two sets of phenolic compounds, which are comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA). Then two 3D-QSAR models for two sets of phenolic analogues were obtained with good results. The first QSAR model, which was derived from CoMFA for phenols with caspase-mediated apoptosis activity against L1210 cells, had good predictability (q2 = 0.874, r2 = 0.930), and the other one was derived from CoMSIA for electron-attracting phenols with cytotoxicity in L1210 cell (q2 = 0.836, r2 = 0.950). In addition, the CoMFA and CoMSIA contour maps provide valuable guidance for designing highly active phenolic compounds. PMID- 20306278 TI - On the surface tension of fluctuating quasi-spherical vesicles. AB - We calculate the stress tensor for a quasi-spherical vesicle and we thermally average it in order to obtain the actual, mechanical, surface tension tau of the vesicle. Both closed and poked vesicles are considered. We recover our results for tau by differentiating the free energy with respect to the proper projected area. We show that tau may become negative well before the transition to oblate shapes and that it may reach quite large negative values in the case of small vesicles. This implies that spherical vesicles may have an inner pressure lower than the outer one. PMID- 20306279 TI - Supported bilayers: combined specular and diffuse X-ray scattering. AB - A method is proposed for the analysis of specular and off-specular reflectivity from supported lipid bilayers. Both thermal fluctuations and the "static" roughness induced by the substrate are carefully taken into account. Examples from supported bilayers and more complex systems comprising a bilayer adsorbed or grafted on the substrate and another "floating" bilayer are given. The combined analysis of specular and off-specular reflectivity allows the precise determination of the structure of adsorbed and floating bilayers, their tension, bending rigidity and interaction potentials. We show that this new method gives a unique opportunity to investigate phenomena like protrusion modes of adsorbed bilayers and opens the way to the investigation of more complex systems including different kinds of lipids, cholesterol or peptides. PMID- 20306280 TI - Gas-producing Escherichia coli fasciitis leading to air-embolism of the lower vena cava. PMID- 20306282 TI - Tautomers and topomers: challenging the uncertainties of direct physicochemical modeling. AB - To address the goal of improved discovery decision making, the uncertainties of physicochemical modeling, as exemplified by tautomer identification, are contrasted with methods focused exclusively on the sole experimental system variable, the changes in ligand structures, as exemplified by topomers. PMID- 20306281 TI - Nocardiosis: updated clinical review and experience at a tertiary center. AB - Nocardiosis is a rare opportunistic disease that affects mainly patients with deficient cell-mediated immunity, such as those with acquired immunodeficiency syndrome (AIDS) or transplant recipients. Pulmonary disease is the most common presentation in immunosuppressed patients and approximately one-third have a disseminated disease. Primary cutaneous nocardiosis is more frequently observed in immunocompetent patients with direct inoculation of the organism through professional exposure. The diagnosis can be challenging, as signs and symptoms are not specific and a high index of clinical of suspicion is necessary. Although gram stain, modified acid-fast stain, and cultures remain as the standard diagnostic tools, novel molecular techniques have changed the taxonomy of these organisms and, in some instances, have facilitated their identification. The disease has a marked tendency to recur and a high morbidity and mortality rate in immunosuppressed patients. Treatment is usually prolonged and an associated antibiotic treatment is preferred for severe disease. Although sulfonamides in combination with other antibiotics are still the treatment of choice, other associations such as imipenem plus amikacin are preferred in some centers. Linezolid is a useful alternative therapeutic agent due to its oral availability and activity against most of the isolates studied. Twenty-eight cases of nocardiosis were diagnosed at our center between January 1989 and April 2009. We report the epidemiologic characteristics of Nocardia spp. observed in our institution and discuss the risk factors, clinical features, diagnosis, and management of the disease. PMID- 20306283 TI - Design, structure-based focusing and in silico screening of combinatorial library of peptidomimetic inhibitors of Dengue virus NS2B-NS3 protease. AB - Serine protease activity of the NS3 protein of Dengue virus is an important target of antiviral agents that interfere with the viral polyprotein precursor processing catalyzed by the NS3 protease (NS3pro), which is important for the viral replication and maturation. Recent studies showed that substrate-based peptidomimetics carrying an electrophilic warhead inhibit the NS2B-NS3pro cofactor-protease complex with inhibition constants in the low micromolar concentration range when basic amino acid residues occupy P(1) and P(2) positions of the inhibitor, and an aldehyde warhead is attached to the P(1). We have used computer-assisted combinatorial techniques to design, focus using the NS2B-NS3pro receptor 3D structure, and in silico screen a virtual library of more than 9,200 peptidomimetic analogs targeted around the template inhibitor Bz-Nle-Lys-Arg-Arg H (Bz-benzoyl) that are composed mainly of unusual amino acid residues in all positions P(1)-P(4). The most promising virtual hits were analyzed in terms of computed enzyme-inhibitor interactions and Adsorption, Distribution, Metabolism and Excretion (ADME) related physico-chemical properties. Our study can direct the interest of medicinal chemists working on a next generation of antiviral chemotherapeutics against the Dengue Fever towards the explored subset of the chemical space that is predicted to contain peptide aldehydes with NS3pro inhibition potencies in nanomolar range which display ADME-related properties comparable to the training set inhibitors. PMID- 20306284 TI - A computational workflow for the design of irreversible inhibitors of protein kinases. AB - Design of irreversible inhibitors is an emerging and relatively less explored strategy for the design of protein kinase inhibitors. In this paper, we present a computational workflow that was specifically conceived to assist such design. The workflow takes the form of a multi-step procedure that includes: the creation of a database of already known reversible inhibitors of protein kinases, the selection of the most promising scaffolds that bind one or more desired kinase templates, the modification of the scaffolds by introduction of chemically reactive groups (suitable cysteine traps) and the final evaluation of the reversible and irreversible protein-ligand complexes with molecular dynamics simulations and binding free energy predictions. Most of these steps were automated. In order to prove that this is viable, the workflow was tested on a database of known inhibitors of ERK2, a protein kinase possessing a cysteine in the ATP site. The modeled ERK2-ligand complexes and the values of the estimated binding free energies of the putative ligands provide useful indicators of their aptitude to bind reversibly and irreversibly to the protein kinase. Moreover, the computational data are used to rank the ligands according to their computed binding free energies and their ability to bind specific protein residues in the reversible and irreversible complexes, thereby providing a useful decision-making tool for each step of the design. In this work we present the overall procedure and the first proof of concept results. PMID- 20306285 TI - Effect of bovine lactoferrin in Salmonella ser. Typhimurium infection in mice. AB - Lactoferrin (LF) has in vitro antimicrobial activity against Gram-negative bacteria. Salmonella enterica subsp. enterica serovar Typhimurium causes systemic infection and acute diarrhea in humans, mainly in children younger than 2 years of age. The aim of the study was to determine the in vivo effect of bovine LF in Salmonella ser. Typhimurium infection in mice. 58 BALB/c mice were employed. Two hours before the infection with 300 microl of 10(7) CFU of Salmonella ser. Typhimurium, 29 mice received LF (2 mg) and 29 placebo (buffer). After the infection, the mice received LF (10 mg/ml) ad libitum or buffer, respectively, for 7 days. Mortality, weight and clinical signs (piloerection, hunched position and reduced movement) were monitored daily. The degree of inflammation and necrosis in the intestine, liver, spleen and brain were studied with a blinded observer. The mortality in the control group (8/29) was higher than in the LF group (1/29) (Kapplan Meier P < 0.05). From the third day post-infection the control group were significantly more symptomatic (P < 0.05). The blood culture for Salmonella spp. was positive for all mice studied in the control group (17/17), but positive in the LF group in only 6/17 animals (P < 0.05). In the LF group, the pathologic studies show less inflammation and focal necrosis in the four organs studied, with the greatest difference found in the intestine. Bovine LF protects against Salmonella ser. Typhimurium infection in mice, reducing the severity, mortality and the degree of inflammation of this infection. PMID- 20306286 TI - Proteomic approach to analyze dormancy breaking of tree seeds. AB - In forest broadleaves from the temperate zone, a large number of species exhibit seed dormancy phenomena. Tree seeds show some of the most pronounced and complicated forms of dormancy in the plant kingdom. Many seeds are deeply physiologically dormant whatever their moisture level and age. However, dormancy can usually be overcome by a cold or warm stratification for several months. The transition from seed dormancy to germination is a multi-step process. In combination with the availability of genome sequence data, proteomics has opened up enormous possibilities for identifying the total set of expressed proteins as well as expression changes during dormancy breaking. The proteomic approach used for analysis of dormancy breaking of tree seeds offers new data allowing better understanding of the mechanism of deep physiological dormancy. The results of proteomic studies on dormancy breaking and the presence of abscisic and gibberellic acids in tree seeds (beech Fagus sylvatica L., Norway maple Acer platanoides L. and sycamore Acer pseudoplatanus L.), help to explain this process better. Most of the changes in protein expression were observed at the end of stratification and in the germinated seeds. This is the most active period of dormancy breaking when seeds pass from the quiescent state to germination. The analysis of the proteins' function showed that the mechanism of seed dormancy breaking involves many processes. Energy metabolism, proteasome, transcription, protein synthesis, signal transduction and methionine metabolism proteins have a special importance. PMID- 20306287 TI - Caffeine intake during pregnancy, late miscarriage and stillbirth. AB - Caffeine is a commonly consumed drug during pregnancy with the potential to affect the developing fetus. Findings from previous studies have shown inconsistent results. We recruited a cohort of 2,643 pregnant women, aged 18-45 years, attending two UK maternity units between 8 and 12 weeks gestation from September 2003 to June 2006. We used a validated tool to assess caffeine intake at different stages of pregnancy and related this to late miscarriage and stillbirth, adjusting for confounders, including salivary cotinine as a biomarker of smoking status. There was a strong association between caffeine intake in the first trimester and subsequent late miscarriage and stillbirth, adjusting for confounders. Women whose pregnancies resulted in late miscarriage or stillbirth had higher caffeine intakes (geometric mean = 145 mg/day; 95% CI: 85-249) than those with live births (103 mg/day; 95% CI: 98-108). Compared to those consuming < 100 mg/day, odds ratios increased to 2.2 (95% CI: 0.7-7.1) for 100-199 mg/day, 1.7 (0.4-7.1) for 200-299 mg/day, and 5.1 (1.6-16.4) for 300+ mg/day (P (trend) = 0.004). Greater caffeine intake is associated with increases in late miscarriage and stillbirth. Despite remaining uncertainty in the strength of association, our study strengthens the observational evidence base on which current guidance is founded. PMID- 20306289 TI - The importance of using the correct bounds on the Bland-Altman limits of agreement when multiple measurements are recorded per patient. AB - The limits of agreement originally derived by Bland and Altman (Lancet i:307-310, 1986) are the most commonly used method for investigating statistical agreement between two medical devices. Bland and Altman describe a confidence interval for these limits that should always accompany the limits themselves. However, this interval presumes that the recorded differences between the two devices in question are independent. This is a reasonable assumption when only one measurement is recorded per device per patient. Bland and Altman (StatMethods Med Res 8:135-160, 1999) subsequently derived bounds for the more general case where multiple observations are recorded within each patient. Unfortunately, in practice, the bounds assuming independence are typically reported when in fact the repeated measures bounds are more appropriate. This communication illustrates the dangers of using the "original" (independence-based) bounds derived in Bland and Altman (Lancet i:307-310, 1986) in the presence of repeated measures per patient. PMID- 20306288 TI - Transient anoxia and oxyradicals induce a region-specific activation of MAPKs in the embryonic heart. AB - We have previously reported in the early septating embryonic heart that electromechanical disturbances induced by anoxia-reoxygenation are distinct in atria, ventricle, and outflow tract, and are attenuated in ventricle by opening of mitochondrial K(ATP) (mitoK(ATP)) channels. Here, we assessed the regional activation of mitogen-activated protein kinases (MAPKs) ERK, p38, and JNK in response to anoxia-reoxygenation and H(2)O(2). Hearts isolated from 4-day-old chick embryos were subjected to 30-min anoxia and 60-min reoxygenation or exposed to H(2)O(2) (50 microM-1 mM). The temporal pattern of activation of ERK, p38, and JNK in atria, ventricle, and outflow tract was determined using immunoblotting and/or kinase assay. The effect of the mitoK(ATP) channel opener diazoxide (50 microM) on JNK phosphorylation was also analyzed. Under basal conditions, total ERK and JNK were homogeneously distributed within the heart, whereas total p38 was the lowest in outflow tract. The phosphorylated/total form ratio of each MAPK was similar in all regions. Phosphorylation of ERK increased in atria and ventricle at the end of reoxygenation without change in outflow tract. Phosphorylation of p38 was augmented by anoxia in the three regions, and returned to basal level at the end of reoxygenation except in the outflow tract. JNK activity was not altered by anoxia-reoxygenation in atria and outflow tract. In ventricle, however, the diazoxide-inhibitable peak of JNK activity known to occur during reoxygenation was not accompanied by a change in phosphorylation level. H(2)O(2) over 500 microM impaired cardiac function, phosphorylated ERK in all the regions and p38 in atria and outflow tract, but did not affect JNK phosphorylation. At a critical stage of early cardiogenesis, anoxia, reoxygenation, exogenous H(2)O(2) and opening of mitoK(ATP) channels can subtly modulate ERK, p38, and JNK pathways in a region-specific manner. PMID- 20306290 TI - Oligonucleotide microarray and QRT-PCR study of adhesion protein gene expression in acute coronary syndrome patients. AB - Cardiovascular diseases, including acute coronary syndrome (ACS), are the leading cause of death among humans. Adhesion proteins, owing to their involvement in the initiation and progression of atherosclerotic lesions, contribute to the progression of coronary disease and ACS occurrence. Considering ambiguosity of results reported to date, we decided to conduct a preliminary investigation of adhesion protein gene expression in ACS patients as well as in healthy subjects by making use of oligonucleotide microarray technology. Analysis of eight microarrays revealed ten upregulated genes differentiating between the two groups: intercellular adhesion molecule-2, platelet/endothelial cell adhesion molecule-1, zyxin, integrin-linked kinase, calcium and integrin binding protein-1 (calmyrin), integrin beta 2, integrin beta 3 (ITGB3), integrin beta 7, integrin alpha 2b, and selectin P ligand. The expression of ITGB3 was found to have been downregulated. PMID- 20306291 TI - A three-stage genome-wide association study of general cognitive ability: hunting the small effects. AB - Childhood general cognitive ability (g) is important for a wide range of outcomes in later life, from school achievement to occupational success and life expectancy. Large-scale association studies will be essential in the quest to identify variants that make up the substantial genetic component implicated by quantitative genetic studies. We conducted a three-stage genome-wide association study for general cognitive ability using over 350,000 single nucleotide polymorphisms (SNPs) in the quantitative extremes of a population sample of 7,900 7-year-old children from the UK Twins Early Development Study. Using two DNA pooling stages to enrich true positives, each of around 1,000 children selected from the extremes of the distribution, and a third individual genotyping stage of over 3,000 children to test for quantitative associations across the normal range, we aimed to home in on genes of small effect. Genome-wide results suggested that our approach was successful in enriching true associations and 28 SNPs were taken forward to individual genotyping in an unselected population sample. However, although we found an enrichment of low P values and identified nine SNPs nominally associated with g (P < 0.05) that show interesting characteristics for follow-up, further replication will be necessary to meet rigorous standards of association. These replications may take advantage of SNP sets to overcome limitations of statistical power. Despite our large sample size and three-stage design, the genes associated with childhood g remain tantalizingly beyond our current reach, providing further evidence for the small effect sizes of individual loci. Larger samples, denser arrays and multiple replications will be necessary in the hunt for the genetic variants that influence human cognitive ability. PMID- 20306292 TI - Differential localization of Acid-sensing ion channels 1 and 2 in human cutaneus pacinian corpuscles. AB - Acid-sensing ion channels (ASICs) are the members of the degenerin/epithelial sodium channel (Deg/ENaC) superfamily which mediate different sensory modalities including mechanosensation. ASICs have been detected in mechanosensory neurons as well as in peripheral mechanoreceptors. We now investigated the distribution of ASIC1, ASIC2, and ASIC3 proteins in human cutaneous Pacinian corpuscles using immunohistochemistry and laser confocal-scanner microscopy. We detected different patterns of expression of these proteins within Pacinian corpuscles. ASIC1 was detected in the central axon co-expressed with RT-97 protein, ASIC2 was expressed by the lamellar cells of the inner core co-localized with S100 protein, and ASIC3 was absent. These results demonstrate for the first time the differential distribution of ASIC1 and ASIC2 in human rapidly adapting low-threshold mechanoreceptors, and suggest specific roles of both proteins in mechanotransduction. PMID- 20306293 TI - Breast cancer risk assessment in a mammography screening program and participation in the IBIS-II chemoprevention trial. AB - It has been shown in several studies that antihormonal compounds can offer effective prophylactic treatment to prevent breast cancer. In view of the low participation rates in chemoprevention trials, the purpose of this study was to identify the characteristics of women taking part in a population-based mammography screening program who wished to obtain information about the risk of breast cancer and then participate in the the International Breast Cancer Intervention Study II (IBIS-II) trial, a randomized double-blind controlled chemoprevention trial comparing anastrozole with placebo. A paper-based survey was conducted in a population-based mammography screening program in Germany between 2007 and 2009. All women who met the criteria for the mammography screening program were invited to complete a questionnaire. A total of 2,524 women completed the questionnaire, and 17.7% (n = 446) met the eligibility criteria for the IBIS-II trial after risk assessment. The women who wished to receive further information about chemoprevention were significantly younger (P < 0.01) and had significantly more children (P = 0.03) and significantly more relatives with breast cancer (P < 0.001). There were no significant differences between the participants with regard to body mass index or hormone replacement therapy. Normal mammographic findings at screening were the main reason (42%) for declining to participate in the IBIS-II trial or attend risk counseling. The ultimate rate of recruitment to the IBIS-II trial was very low (three women). Offering chemoprevention to women within a mammography screening unit as part of a paper-based survey resulted in low participation rates for both, the survey and the final participation in the IBIS-II trial. More individualized approaches and communication of breast cancer risk at the time of the risk assessment might be helpful to increase the participation and the understanding of chemopreventive approaches. PMID- 20306294 TI - GPX1 Pro198Leu polymorphism and breast cancer risk: a meta-analysis. AB - A genetic polymorphism at codon 198 in the human glutathione peroxidase 1 gene was reported to be associated with several cancers. However, this relationship remains controversial, especially in breast cancer. For better understanding the effect of GPX1 Pro198Leu polymorphism on breast cancer, a meta-analysis was performed. By searching relevant literatures, a total of six case-control studies, containing 5,509 breast cancer cases and 6,542 healthy controls, were included. The strength of association between GPX1 Pro198Leu polymorphism and breast cancer risk was assessed by odds ratio (OR) with the corresponding 95% confidence interval (95%CI). And the results strongly suggested that there was no significant association between variant Leu allele and breast cancer susceptibility in overall comparisons in all genetic models [additive model: OR, 1.04; 95% CI, 0.92-1.18; P = 0.555; dominant model: OR, 1.01; 95% CI, 0.94-1.09; P = 0.777; recessive model: OR, 1.04; 95% CI, 0.92-1.18; P = 0.536]. However in subgroup analysis, an elevated risk in African population with variant Leu allele was revealed in additive (OR, 1.91; 95% CI, 1.02-3.58; P = 0.044) and recessive (OR, 2.09; 95% CI, 1.16-3.76; P = 0.014) genetic model. No apparent association between this polymorphism and different menopausal status (premenopausal and postmenopausal) and the other ethnicities (almost Caucasians) was showed. In conclusion, this meta-analysis strongly suggests that GPX1 Pro198Leu polymorphism is not associated with breast cancer risk in Caucasians, and an elevated risk in Africans needs large-scale investigations to confirm. PMID- 20306295 TI - The response to postnatal stress: amino acids transporters and PKC activity. AB - It is well known that animals exposed to stressful stimuli during their early life develop different neurological disorders when they become adults. In this study, we evaluated the effect of acute cold stress on gamma-aminobutyric acid (GABA) and L-Serine (L-Ser) transporters in vitro, using the uptake of [(3)H] GABA and [(3)H]L-Ser by synaptosomes-enriched fractions isolated from rat cerebral cortex during postnatal development. GABA and L-Ser uptake studies in vitro will be used in this investigation as a colateral evidence of changes in the expression of transporters of GABA and L-Ser. We observed that the maximum velocity (V (max)) in L-Ser and GABA uptake after stress session increased in all stages studied. In contrast, K (m) values of L-Ser uptake enhancent in almost age calculated, excluding at PD21 after cold stress during development, at the same time as K (m) (uptake affinity) values of GABA increased in just about age considered but not at PD5 compared with the control group. Finally we investigated the mechanism by which cells regulate the substrate affinity of L Ser and GABA transporters. We demonstrated a significantly increase in total PKC activity to PD5 from PD21. Pretreatment with PKC inhibitor: staurosporine (SP) led to a restoration of control uptake in several postnatal-days suggesting a relationship between amino acids system and PKC activation. These findings suggest that a single exposure to postnatal cold stress at different periods after birth modifies both GABA and L-Ser transporters and the related increase in total PKC activity could be intracellular events that participate in neuronal plasticity by early life stress, which could be relevant to function of transporters in the adult rat brain. PMID- 20306296 TI - Predictive models for nucleoside bisubstrate analogs as inhibitors of siderophore biosynthesis in Mycobacterium tuberculosis: pharmacophore mapping and chemometric QSAR study. AB - Inhibitors of aryl acid adenylating enzymes (AAAE), known as MbtA, involved in siderophore biosynthesis in Mycobacterium tuberculosis, are being explored as potential antitubercular agents. In this article, we report the development of a robust pharmacophore model and investigation of structure-activity relationship of several nucleoside bisubstrate analogs reported as MbtA inhibitors. The developed pharmacophore model revealed the importance of two hydrogen bond donors and one hydrogen bond acceptor features. Furthermore, it was found that an aromatic ring at the distal part of molecule away from the two aromatic rings of adenyl moiety is a critical requirement for the tight binding of inhibitor. The generated pharmacophore-based alignment was used to derive a predictive atom based 3D-QSAR model for training set (r (2) = 0.97, SD = 0.23, F = 310.6, N = 48) and test set (Q (2) = 0.71, RMSE = 0.65, Pearson-R = 0.85, N = 15). Structure activity relationship investigation further revealed that bulky substitutions at the C-6 position of adenyl moiety is detrimental to activity, while hydrophobic substitutions can be tolerated at C-2 position. Taken together, the PLS-generated QSAR regression cubes along with developed pharmacophore model provide a qualitative picture of the active site and can be used as a powerful tool for the rational modification of bisubstrate inhibitors of MbtA in search of better antitubercular agents. Furthermore, a three-class classification chemometric QSAR model was developed using molecular descriptors for the prediction of whole-cell activity which could be used in the predictive layer for screening of compounds before synthesis. PMID- 20306297 TI - Acquired Gitelman's syndrome: an oxymoron? AB - We present the case of a 27-year-old woman with end stage renal disease from Diabetes Mellitus type 1 who had been on hemodialysis for a year. Her father, who was otherwise healthy, was evaluated as a possible living donor. Incidentally, during the workup process, he was identified as having Gitelman's syndrome (GS). The transplant proceeded without any complications, following which the recipient developed biochemical abnormalities consistent with GS. Both donor and recipient are doing well at this time. To our knowledge, this is the only known case of kidney donation by a patient with GS either living or deceased. PMID- 20306298 TI - Can adolescents learn self-control? Delay of gratification in the development of control over risk taking. AB - Recent findings from developmental neuroscience suggest that the adolescent brain is too immature to exert control over impulsive drives, such as sensation seeking, that increase during adolescence. Using a discounting of delayed reward paradigm, this research examines the ability to delay gratification as a potential source of control over risk-taking tendencies that increase during adolescence. In addition, it explores the role of experience resulting from risk taking as well as future time perspective as contributors to the development of this ability. In a nationally representative sample (n = 900) of young people aged 14-22, a structural equation analysis shows that risk taking as assessed by use of three popular drugs (tobacco, marijuana, and alcohol) is inversely related to the ability to delay gratification. The relation is robust across gender, age, and different levels of sensation seeking. In addition, high sensation seekers exhibit dramatic age-related increase in delay of gratification, lending support to the hypothesis that engaging in risky behavior provides experience that leads to greater patience for long-term rewards. The findings support the conclusion that a complete understanding of the development of self-control must consider individual differences not easily explained by universal trends in brain maturation. PMID- 20306299 TI - Sustained release of insulin through skin by intradermal microdelivery system. AB - An intradermal microdelivery system comprising a wafer having 150-mum long microneedles and an applicator was used for controlled release of insulin. Insulin was topically applied on microneedle-pretreated skin. In vitro percutaneous studies showed that the penetration amount of FITC-Insulin following microneedle pretreatment was enhanced significantly and continued to increase for several hours after the removal of donor phase. In vivo studies on diabetic rats confirmed that the pharmacodynamic profile of percutaneously administrated regular insulin was smooth, with the duration of action comparable to that of subcutaneously injected biphasic insulin. The effects of insulin concentration, duration and area of microneedle treatment on blood glucose lowering were studied in vivo. The results indicated that the duration of microneedle treatment and insulin concentration were key influencing factors to optimize blood glucose control. The extent of blood glucose lowering was in proportion to the area of microneedle treatment. PMID- 20306300 TI - The human lysyl oxidase-like 2 protein functions as an amine oxidase toward collagen and elastin. AB - The lysyl oxidase-like 2 (LOXL2) protein is a human paralogue of lysyl oxidase (LOX) that functions as an amine oxidase for formation of lysine-derived cross links found in collagen and elastin. In addition to the C-terminal domains characteristic to the LOX family members, LOXL2 contains four scavenger receptor cysteine-rich (SRCR) domains in the N-terminus. In order to assess the amine oxidase activity of LOXL2, we expressed a series of recombinant LOXL2 proteins with deletions in the SRCR domains, using an Escherichia coli expression system. All of the purified recombinant LOXL2 proteins, with or without the SRCR domains in the N-terminus, showed significant amine oxidase activity toward several different types of collagen and elastin in in vitro amine oxidase assays, indicating deletion of the SRCR domains does not interfere with amine oxidase activity of LOXL2. Further, amine oxidase activity of LOXL2 was not susceptible to inhibition by beta-aminopropionitrile, an irreversible inhibitor of LOX, suggesting a different enzymatic mechanism between these two paralogues. PMID- 20306301 TI - Three novel SNPs in the coding region of PPARgamma gene and their associations with meat quality traits in cattle. AB - The peroxisome proliferator-activated receptor gamma (PPARgamma) is a nuclear hormone receptor that regulates adipogenesis and many other biological processes. In the present study, we carried out PCR-SSCP and DNA sequencing analyses to examine SNPs in coding region of the PPARgamma gene. A total of 660 individuals from five Chinese cattle breeds were genotyped. We identified three SNPs and their associations with meat quality traits were analyzed in 108 Qinchuan cattle. Two missense mutations and one synonymous mutation were found: 200 A>G (genotypes AA, AB and BB) resulting in D7G change, the silent substitution 42895 C>T (genotypes JJ and JI) and 72472 G>T (genotypes CC, DC and DD) producing Q448H change, respectively. The frequencies of PPARgamma-A allele were 0.86, 0.83, 0.80, 0.72 and 0.87 for Qinchuan, Nanyang, Jiaxian, Luxi and Xianan populations, respectively. The frequencies of PPARgamma-J allele varied from 0.87 to 0.96 in the five populations. In the 72472 G>T locus, the frequencies of PPARgamma-C allele were higher than PPARgamma-D allele in the five populations, and ranged from 0.58 to 0.82. Least squares analysis revealed that in 42895 C>T locus, there was a significant effect on tenderness in 18-20 months Qinchuan cattle (P<0.01), and in the 72472 G>T locus, animals with the genotype DC had lower mean values than these with genotype CC (P<0.01) for back fat thickness in 18-20 months, and animals with the genotype DD had lower mean values than these with genotypes CC and DC (P<0.01) for water holding capacity in 21-24 months (P<0.01). The SNPs we have identified may contribute to establishing a more efficient selection program for improving of genetic characteristics in indigenous Chinese cattle. PMID- 20306302 TI - The role of cell cycle-dependent neuropathy target esterase in cell proliferation. AB - Neuropathy target esterase (NTE) is a novel phospholipase B and plays a role in phospholipid homeostasis. Although over-expression of NTE inhibits cell division, the role of NTE in cell proliferation is still unknown. In the current study, we firstly used synchronous HeLa cells to study the expression profile of NTE during the cell cycle. NTE protein and activity are regulated during the cell cycle with highest level at G1 and lowest at G2/M phase. However, NTE mRNA levels are constant during the cell cycle. The role of NTE in cell proliferation was investigated by short hairpin RNA (shRNA) to suppress the expression of NTE. Knockdown of NTE significant down-regulated of NTE expression and reduced the glycerophosphocholine level. However, suppression of NTE did not affect phosphatidylcholine content or cell cycle progression. In addition, NTE was demonstrated to be degraded by the ubiquitin-proteasome pathway. These results suggested for the first time that NTE is a cell cycle-dependent protein, but is not essential for cell proliferation, and the ubiquitin-mediated proteolysis may be involved in the regulation of NTE during the cell cycle. PMID- 20306303 TI - A genetic investigation of Korean mummies from the Joseon Dynasty. AB - Two Korean mummies (Danwoong-mirra and Yoon-mirra) found in medieval tombs in the central region of the Korean peninsula were genetically investigated by analysis of mitochondrial DNA (mtDNA), Y-chromosomal short tandem repeat (Y-STR) and the ABO gene. Danwoong-mirra is a male child mummy and Yoon-mirra is a pregnant female mummy, dating back about 550 and 450 years, respectively. DNA was extracted from soft tissues or bones. mtDNA, Y-STR and the ABO gene were amplified using a small size amplicon strategy and were analyzed according to the criteria of ancient DNA analysis to ensure that authentic DNA typing results were obtained from these ancient samples. Analysis of mtDNA hypervariable region sequence and coding region single nucleotide polymorphism (SNP) information revealed that Danwoong-mirra and Yoon-mirra belong to the East Asian mtDNA haplogroups D4 and M7c, respectively. The Y-STRs were analyzed in the male child mummy (Danwoong-mirra) using the AmpFlSTR(r) Yfiler PCR Amplification Kit and an in-house Y-miniplex plus system, and could be characterized in 4 loci with small amplicon size. The analysis of ABO gene SNPs using multiplex single base extension methods revealed that the ABO blood types of Danwoong-mirra and Yoon mirra are AO01 and AB, respectively. The small size amplicon strategy and the authentication process in the present study will be effectively applicable to future genetic analyses of various forensic and ancient samples. PMID- 20306304 TI - CgSL2, an S-like RNase gene in 'Zigui shatian' pummelo (Citrus grandis Osbeck), is involved in ovary senescence. AB - 'Zigui shatian' pummelo (Citrus grandis Osbeck) is one nature mutant from 'Shatian' pummelo, which showed self-compatibility, because self-pollen tubes were not arrested in the style, moreover abnormal post-zygotic development in ovary caused seed abortion in the cultivar. Herein we constructed a cDNA library from flowers of 'Zigui shatian' pummelo and identified one RNase gene fragment. The full length of cDNA sequence of this gene, with an open reading frame of 834 bp, was isolated by 5'-RACE method. The gene, named as CgSL2, contained five conserved regions and two histidine residues essential for RNase activity. Phylogenetic analysis indicated that CgSL2 was mostly similar to AhSL28, an S like RNase from Antirrhinum. Southern hybridization verified CgSL2 existed in the genome as multiple copies. qRT-PCR and RT-PCR analysis showed that the expression of CgSL2 was not tissue-specific. The expression of CgSL2 was down-regulated during senescence of stem, petal, style and stamen, whereas up-regulated during ovary senescence. Further in situ hybridization of CgSL2 in the ovary during the balloon stage to anthesis stage also showed that it dramatically increased in mature flower, consistent with qRT-PCR and RT-PCR results. These findings suggested that CgSL2 might play an important role during ovary senescence. PMID- 20306305 TI - Expression of Pdx1 mediates differentiation from mesenchymal stem cells into insulin-producing cells. AB - The transplantation of insulin-producing cells is a promising approach for the treatment of insulin-dependent diabetes mellitus; however, lack of pancreas donors limits its application. Pancreatic duodenal homeobox 1 (Pdx1) plays a key role in the differentiation of various non-beta-cells into insulin-producing cells, but the potential mechanism remains to be clarified. The purpose of this study was to confirm that the expression of Pdx1 could mediate the differentiation of rat mesenchymal stem cells (MSCs) into insulin-producing cells and evaluate the potential molecular mechanisms in the process that Pdx1 activates transcription of insulin gene. In this study, glucose-stimulated insulin secretion was obviously detected in MSCs transfected with Pdx1 cDNA by insulin release assay and the islet-like structure formed in Pdx1-expressing MSCs was stained into black-red by dithizone, while the native MSCs were opposite. In addition, we uncovered the close relationships among the expression of Pdx1, insulin and Ngn3 genes, whose expression indicated parallel changes after high glucose challenge, and the fluctuation of Pdx1 and Ngn3 partly resulted in the unstable release of insulin. Taken together, these findings demonstrated that the effective role of Pdx1 gene in inducing insulin-producing cells, which may shuttle to the nucleoplasm of MSCs under high glucose, then initiate the expression of native transcription factors Ngn3 and recruit other proteins, resulting in transactivation of the relevant genes including insulin and generation of beta cell phenotype. Accordingly, these results would provide new insights that may be applicable to improve beta cell replacement strategies and enhance diabetes therapy in the future. PMID- 20306306 TI - Using high competent shoot apical meristems of cockscomb as explants for studying function of ASYMMETRIC LEAVES2-LIKE11 (ASL11) gene of Arabidopsis. AB - Though shoot apical meristems (SAMs) commonly exhibit low or no competence for transformation, the potent regeneration of this tissue merits further research. Especially, when shoot regeneration is recalcitrant using other tissues as explants, SAM probably is an excellent selection. In cockscomb plants, using SAMs from seedlings obtained from MS medium with 0.5 mg l(-1) 6-BA as explants, high frequency of transformation (approximate 20%) is obtained; whereas control SAMs performed poorly for transformation (approximate 3%). These SAMs are malformed in morphology compared to control SAMs. Further observation found that, in these SAMs, cell proliferation and/or TE formation are seen; which are not found in control SAMs. GUS assays indicated that GUS-positive blue spots at TE zones are obvious; whereas the case was contrary in control SAMs. All these data suggest that cell proliferation and/or TE formation might cause high effective transformation. This transformation system should facilitate the use of this species for studies on gene manipulation and expression. Therefore, we introduced 35S:ASL11-GFP to cockscomb via Agrobacterium tumefaciens. ASYMMETRIC LEAVES2 LIKE11 (ASL11) gene of Arabidopsis is a member of the ASYMMETRIC LEAVES2 (AS2)/LATERAL ORGAN BOUNDARIES (LOB) domain gene family, and its function is largely unclear. By confocal laser scanning microscopy, we found that in most over 35S:ASL11-GFP cockscomb plants, ASL11-GFP fusion protein was in discrete nuclear location. These results indicate that the T-DNA contains within the construct inserted into the host chromosomes in an integral form, and also suggest that ASL11 might be a nuclear protein and function as a potential transcription factor. Moreover, SAMs of the over 35S:ASL11-GFP plants show needle like patterns that lack organ primordial; suggesting ASL11 might be involved in sustaining indeterminate cell fate of SAMs. PMID- 20306307 TI - Justice and the allocation of healthcare resources: should indirect, non-health effects count? AB - Alternative allocations of a fixed bundle of healthcare resources often involve significantly different indirect, non-health effects. The question arises whether these effects must figure in accounts of the conditions under which a distribution of healthcare resources is morally justifiable. In this article we defend a Scanlonian, affirmative answer to this question: healthcare resource managers should sometimes select an allocation which has worse direct, health related effects but better indirect, nonhealth effects; they should do this when the interests served by such a policy are more urgent than the healthcare interests better served by an alternative allocation. We note that there is a prima facie case for the claim that such benefits (and costs) are relevant--i.e. they are real benefits, and in other contexts our decisions can permissibly be guided by them. We then proceed to rebut three lines of argument that might be thought to defeat this prima facie case: they appeal to fairness, the Kantian Formula of Humanity as an End in Itself, and the equal moral worth of persons, respectively. PMID- 20306308 TI - Preparation of fatty acid methyl esters by selective methanolysis of polar glycerolipids. AB - KOH in aqueous methanol catalyzes selective methanolysis of polar glycerolipids with O-ester-linked acyl residues, while triacylglycerols and sterol esters are inert in the solution. Based on these findings, a convenient and reliable method was developed for the preparation of fatty acid methyl esters (FAMEs) from polar glycerolipids in lipid mixtures without prior isolation. Methanolysis of polar glycerolipids was completed within 2.5 min by vortexing or 20 min by shaking with 0.7 M KOH/70% (v/v) methanol in the presence of hexane at 30 degrees C. The yields of FAMEs obtained by the present method were greater than 95%. The method was applied successfully to gas chromatographic analysis of the fatty acid compositions of polar glycerolipids in seed oil and blood. No obvious differences were found between the fatty acid compositions determined by the present method and those determined by conventional methods, including lipid extraction with chloroform/methanol followed by isolation of polar lipids by chromatography. The fatty acid composition of polar glycerolipids, including phospholipids, can be determined readily in many crude samples. PMID- 20306309 TI - The anorexigenic action of the octadecaneuropeptide (ODN) in goldfish is mediated through the MC4R- and subsequently the CRH receptor-signaling pathways. AB - Intracerebroventricular (ICV) administration of the octadecaneuropeptide (ODN), a peptide derived from diazepam-binding inhibitor, reduces food intake in goldfish as in rodents. However, the neurochemical pathways involved in the anorexigenic action of ODN have not yet been identified in goldfish. Alpha-melanocyte stimulating hormone (alpha-MSH), corticotropin-releasing hormone (CRH), and CRH related peptides play a major role in the control of food consumption in goldfish. In this species, the anorexigenic action of alpha-MSH is mediated via the CRH/CRH receptor neuronal system. Therefore, in the present study, we examined whether the anorexigenic effect of ODN in goldfish could be mediated through alpha-MSH and/or CRH neuronal pathways. ICV injection of ODN (10 pmol/g body weight (BW)) significantly reduced food intake, and the anorexigenic effect of ODN was suppressed by ICV preinjection of the melanocortin 4 receptor (MC4R) antagonist HS024 (40 pmol/g BW) or the CRH receptor 1/receptor 2 antagonist alpha helical CRH((9-41)) (100 pmol/g BW). ICV injection of ODN (10 pmol/g BW) induced a significant increase of proopiomelanocortin mRNA level but had no effect on CRH mRNA level, while ICV injection of the MC4R agonist, melanotan II (100 pmol/g BW), significantly enhanced CRH mRNA expression. These results suggest that, in goldfish, the anorexigenic action of ODN is mediated by the MC4R- and subsequently through the CRH receptor-signaling pathways. PMID- 20306311 TI - NMR resonance assignments of an engineered neomycin-sensing riboswitch RNA bound to ribostamycin and tobramycin. AB - The neomycin-sensing riboswitch is an engineered riboswitch developed to regulate gene expression in vivo in the lower eukaryote Saccharomyces cerevisiae upon binding to neomycin B. With a size of only 27nt it is the smallest functional riboswitch element identified so far. It binds not only neomycin B but also related aminoglycosides of the 2'-deoxystreptamine class with high affinity. The regulatory activity, however, strongly depends on the identity of the aminoglycoside. As a prerequisite for the structure determination of riboswitch ligand complexes we report here the (1)H, (15)N, (13)C and partial (31)P chemical shift assignments for the minimal functional 27nt neomycin sensing riboswitch RNA in complex with the 4,5-linked neomycin analog ribostamycin and the 4,6-linked aminoglycoside tobramycin. PMID- 20306310 TI - Resveratrol as a therapeutic agent for neurodegenerative diseases. AB - Excess production of reactive oxygen species in the brain has been implicated as a common underlying risk factor for the pathogenesis of a number of neurodegenerative disorders, including Alzheimer's disease (AD), Parkinson's disease (PD), and stroke. In recent years, there is considerable interest concerning investigation of antioxidative and anti-inflammatory effects of phenolic compounds from different botanical sources. In this review, we first describe oxidative mechanisms associated with stroke, AD, and PD, and subsequently, we place emphasis on recent studies implicating neuroprotective effects of resveratrol, a polyphenolic compound derived from grapes and red wine. These studies show that the beneficial effects of resveratrol are not only limited to its antioxidant and anti-inflammatory action but also include activation of sirtuin 1 (SIRT1) and vitagenes, which can prevent the deleterious effects triggered by oxidative stress. In fact, SIRT1 activation by resveratrol is gaining importance in the development of innovative treatment strategies for stroke and other neurodegenerative disorders. The goal here is to provide a better understanding of the mode of action of resveratrol and its possible use as a potential therapeutic agent to ameliorate stroke damage as well as other age related neurodegenerative disorders. PMID- 20306312 TI - Increased CTLA-4 and FOXP3 transcripts in peripheral blood mononuclear cells of patients with breast cancer. AB - Generation of Regulatory T cells (Tregs) is known to play a major role in progression and modulation of the immune escape mechanisms in cancer. These cells express Forkhead/winged helix transcription factor (FOXP3) and also Cytotoxic T lymphocyte antigen-4 (CTLA-4), as a negative regulatory molecule which, is a potential target for immunotherapy. We, therefore, evaluated FOXP3 and CTLA-4 transcripts in the peripheral blood mononuclear cells from 55 women with histologically-confirmed infiltrating ductal carcinoma of the breast. Blood samples from 40 healthy volunteer women without a history of malignancies or autoimmune disorders were also obtained as a control. The abundance of FOXP3 and CTLA-4 gene transcripts was determined by quantitative real-time PCR (qRT-PCR). Compared to healthy individuals, significantly higher amounts of these transcripts were found in the mononuclear cells from breast cancer patients. Also, a significant correlation was found between CTLA-4 and FOXP3 expressions in a group of patients. Among patients with early stage, nonmetastatic or low-grade disease, the relative expression of CTLA-4 was about 10-fold as much as in the control group. These patients also showed a significant increase, more than 10 fold, in mean relative FOXP3 expression. The results of this investigation point to functional activity of Treg cells in early stages of breast cancer, a finding which emphasizes the significance of Tregs as an imminent target for breast cancer immunotherapy. PMID- 20306313 TI - FOXP3+ cell density in primary tumor has no prognostic impact in patients with cutaneous malignant melanoma. AB - Regulatory T cells (Tregs) have been implicated as inhibitors of antitumor immune reactions. However, data on the relevance of their prevalence at tumor sites in influencing disease outcome are controversial. The aim of our study was to investigate the role in tumor progression and the prognostic impact of the density of lymphocytes expressing FOXP3, a transcription factor expressed predominantly by CD4(+)CD25(+) Tregs, in primary cutaneous melanoma. We examined the infiltration of FOXP3(+) cells by immunohistochemistry in tumor samples from 97 patients and evaluated in relation to patient and tumor parameters. The degree of infiltration by FOXP3(+) cells did not show correlation with the thickness of melanomas. Moreover, no associations were found with metastasis formation during the 5-year follow-up period, patient survival, or any other clinicopathologic parameters studied. These results suggest that the presence of FOXP3(+) lymphocytes in primary tumors is not of prognostic importance in human cutaneous melanoma. PMID- 20306314 TI - A functionally active dimer of mycobacterium tuberculosis malate synthase G. AB - Malate synthase G is an important housekeeping enzyme of glyoxylate shunt in mycobacterium. The pleotropic function of this protein by virtue of its intracellular/extracellular localization and its behavior as an adhesin and virulence factor is quite enigmatic. Despite its importance in mycobacterium persistence, we do not know much about its biophysical and biochemical properties. Earlier reports suggest that the enzyme exists only as a monomer in prokaryotes; however, we observed the existence of both active monomer and dimer forms of the enzyme under physiological conditions. The dimeric form of the enzymes is more stable as compared to the monomeric form as evident from various biophysical parameters. In addition, the dimeric enzyme also shows enhanced stability against proteolysis than the monomers. Based on these studies, it seems that dimerization is an important factor in regulating stability. The differential localization and diverse functions of malate synthase other than its enzymatic role might be triggering the stabilization of the enzyme dimer and modulation of activity and stability in vivo. PMID- 20306315 TI - Residual structure in a peptide fragment of the outer membrane protein X under denaturing conditions: a molecular dynamics study. AB - The Escherichia coli outer membrane protein X (OmpX) contains two polypeptide segments that present nonrandom residual structure in 8 M aqueous urea, whereas the remainder of the protein is in a flexibly disordered conformation (Tafer et al. in Biochemistry 43:860-869, 2004). In the present study, the results of two long-timescale (0.4 micros) unrestrained explicit-solvent molecular dynamics (MD) simulations of a tetradecapeptide representative of one of these two segments in 8 M aqueous urea are reported and analyzed. The two simulations were initiated either from the conformation of the corresponding segment in an NMR model structure of the unfolded protein or from an entirely extended configuration. The sampled conformational ensembles agree qualitatively with the experimentally observed NOEs, but not quantitatively, suggesting that a number of relevant configurations were not visited on the 2 x 0.4 micros timescale. Major conformational transitions occur on the 0.1 micros timescale, and the ensembles corresponding to the two independent simulations overlap only to a limited extent. However, both simulations show in multiple events the reversible formation and disruption of alpha-helical secondary structure (characteristic of the urea-denatured state) and beta-turn secondary structure (characteristic of the native state). Events of helix formation are correlated with the appearance of hydrogen bonds between two side chains (Asp75-Ser78) and of a persistent hydrophobic contact (Trp76-Tyr80). They also evidence a peculiar helix stabilization and N-terminal capping role for a negatively charged residue (Asp75). These features are in good qualitative agreement with the NMR model for the structured state of the corresponding segment in the urea-denatured protein. The analysis of the simulations provides a detailed picture of the structural and dynamic features of the considered peptide at atomic resolution that is of high relevance in the understanding of the OmpX folding process. PMID- 20306316 TI - Synergism of VAM and Rhizobium on production and metabolism of IAA in roots and root nodules of Vigna mungo. AB - Mature and healthy root nodules of Vigna mungo appeared to contain higher amount of indole-acetic acid (IAA) than non-nodulated roots. Dual effect of VAM fungus, Glomus fasciculatum and the nitrogen-fixing bacteria, Rhizobium sp. on the nodulation of roots of V. mungo was studied. It was recorded that the roots which were inoculated simultaneously with both the symbionts i.e., G. fasciculatum and Rhizobium exhibited greater amount of IAA production than the non-inoculated roots. A tryptophan pool present in the mature nodules and young leaves might serve as a precursor for IAA production in the roots and in the nodules. Activity of IAA-metabolizing enzymes, such as IAA oxidase, peroxidase, and polyphenol oxidase was investigated which indicates the active metabolism of IAA in roots and nodules. The Rhizobium symbiont isolated from fresh nodules of V. mungo produced significant amount of IAA under in vitro condition when tryptophan was added to the medium as precursor. Present study represents some beneficial effects of Rhizobium and G. fasciculatum on the production and metabolism of IAA in roots and nodules of V. mungo. The important physiological implication of the study on IAA production and its metabolism in Rhizobium-Legume-VAM tripartite symbiosis is certainly representing a new approach to satisfy the hormonal balance in the host plant. PMID- 20306318 TI - Langenbeck's Archives: the international journal of the German Society of Surgery. PMID- 20306317 TI - Improved detection of microbial ureteral stent colonisation by sonication. AB - PURPOSE: The diagnosis of microbial ureteral stent colonisation (MUSC) is difficult, since routine diagnostic techniques do not accurately detect microorganisms embedded in biofilms. New methods may improve diagnostic yield and understanding the pathophysiology of MUSC. The aim of the present study was to evaluate the potential of sonication in the detection of MUSC and to identify risk factors for device colonisation. METHODS: Four hundred and eight polyurethane ureteral stents of 300 consecutive patients were prospectively evaluated. Conventional urine culture (CUC) was obtained prior to stent placement and device removal. Sonication was performed to dislodge adherent microorganisms. Data of patient sex and age, indwelling time and indication for stent placement were recorded. RESULTS: Sonicate-fluid culture detected MUSC in 36%. Ureteral stents inserted during urinary tract infection (UTI) were more frequently colonised (59%) compared to those placed in sterile urine (26%; P<0.001). Female sex (P<0.001) and continuous stenting (P<0.005) were significant risk factors for MUSC; a similar trend was observed in patients older than 50 years (P=0.16). MUSC and indwelling time were positively correlated (P<0.005). MUSC was accompanied by positive CUC in 36%. Most commonly isolated microorganisms were Coagulase negative staphylococci (18.3%), Enterococci (17.9%) and Enterobacteriaceae (16.9%). CONCLUSIONS: Sonication is a promising approach in the diagnosis of MUSC. Significant risk factors for MUSC are UTI at the time of stent insertion, female sex, continuous stenting and indwelling time. CUC is a poor predictor of MUSC. The clinical relevance of MUSC needs further evaluation to classify isolated microorganism properly as contaminants or pathogens. PMID- 20306319 TI - Langenbecks Archiv fur Chirurgie in the second half of the twentieth century (personal reflections of an editor emeritus). AB - The history of this oldest among German surgical journals, in the second half of the twentieth century, is outlined from an editor's point of view. In this period, the journal mutated from a conservative refuge for lengthy theses to an innovative peer-review organ. Apart from original research and clinical reports, the journal now ran regular editorials, discussion panels and sections on Current Operative Techniques as well as Clinical Anatomy and finally developed into an English-language publication. This half-century of surgical progress-second to none in the history of surgery-is of course reflected in the contents of the journal. At the same time, specialisation and fragmentation of surgery from within and the advent of ever more competitive journals from without have presented a serious challenge to the survival of this traditional organ. PMID- 20306320 TI - A feeding strategy for tetramethylpyrazine production by Bacillus subtilis based on the stimulating effect of ammonium phosphate. AB - To examine the effects of ammonium salts on tetramethylpyrazine (TTMP) production by Bacillus subtilis CCTCC M 208157, different ammonium salts were tested, and diammonium phosphate (DAP) was found to have a predominant effect on stimulating TTMP synthesis. The DAP requirements for TTMP production were then investigated, experimental results showed that higher concentrations of DAP favored TTMP production, while both the ammonium and phosphate ions exhibited inhibitory effects on the cell growth and precursor 3-hydroxy-2-butanone accumulation. Based on the results above, a DAP feeding strategy was developed and verified in further experiments. By applying the proposed fed-batch strategy, the maximum TTMP concentrations reached 7.46 and 7.34 g/l in flask and fermenter experiments, increased by 55.1 and 29.0% compared to that of the batch TTMP fermentation, respectively. To our knowledge, these results, i.e., TTMP yields in flask or fermenter fermentations, were new records on TTMP fermentation by B. subtilis. PMID- 20306321 TI - Clinical evaluation of the alar base width of patients submitted to surgically assisted maxillary expansion. AB - PROPOSITION: The aim of this study was to evaluate both the presence and magnitude of the modifications occurred in the alar base width, in patients submitted to surgically assisted maxillary expansion (SAME). METHODS: The alar base width of 13 patients submitted to SAME followed by alar base suture and simple V-Y suture was measured by using direct measuring with digital paquimeter during regular periods: pre-operative and 2, 6, 24, and 36 months post-operative. Data were submitted to statistical analysis by using ANOVA and Tukey's test with level of significance of 5%. RESULTS: There was a statistically significant increase (P < 0.05) of the alar base width in the comparison between the pre operative and the 6-, 24-, and 36-month post-operative periods. CONCLUSION: SAME procedure increased the alar base width even performing the alar bases sutures; however, despite the widening of 1.6 mm, the clinical result was not compromised and better than without the technique. PMID- 20306322 TI - Evaluation of a rapid immunochromatographic test for the detection of norovirus in stool samples. AB - Worldwide noroviruses are an important cause of gastroenteritis and are major agents of both sporadic as well as epidemic infection. Because of the rapid transmission of the virus, early detection is essential. Until recently, the available test methods for the detection in stool were enzyme immunoassays and real-time reverse transcription polymerase chain reaction (RT-PCR), both of which take several hours to perform. We evaluated the rapid immunochromatographic test RIDA(R)QUICK Norovirus for the detection of norovirus in the stool of patients with acute gastroenteritis. This test is easy to perform and read and only takes 20 min. The sensitivity and specificity compared to RT-PCR results and the positive and negative predictive values were 57.1%, 99.1%, 93.3% and 91.2%, respectively. The rapid test is useful for quick screening, but a negative result should be followed up by RT-PCR. PMID- 20306323 TI - Characterisation of invasive Haemophilus influenzae isolates in Slovenia, 1993 2008. AB - The objectives of our study were to describe the epidemiology of invasive Haemophilus influenzae disease from 1993 to 2008 in Slovenia, a country with routine H. influenzae serotype b (Hib) conjugate vaccination since the year 2000. A total of 292 isolates of H. influenzae, recovered from a normally sterile site, were collected in the study period. The isolates were serotyped by slide agglutination and antibiotic susceptibility was determined. One hundred and eight isolates received after the year 2000 were serotyped by slide agglutination and by polymerase chain reaction (PCR) capsule typing, and both methods were compared. After the introduction of the routine Hib vaccination, the incidence of H. influenzae disease in children under the age of 5 years has decreased by 87.6% and type b was replaced by non-typeable H. influenzae as the predominant serotype. The proportion of serotype b decreased from 85.3% in the pre vaccination period to 13.0% in the vaccination period and the proportion of non capsulated isolates increased from 12.0 to 85.2%. The study of genetic relatedness by pulsed-field gel electrophoresis (PFGE) demonstrated that the isolates of serotypes b and f were genetically homogeneous within the serotype. The results of our national surveillance showed that the vaccine has been very efficient in preventing Hib invasive disease in Slovenia. Nevertheless, we see a need for further monitoring of invasive H. influenzae infections at a national level. PMID- 20306324 TI - T regulatory cells and Th1/Th2 cytokines in peripheral blood from tuberculosis patients. AB - About 10% of people infected with Mycobacterium tuberculosis develop active tuberculosis (TB), and Th1 effector cells and Th1 cytokines play key roles in controlling M. tuberculosis infection. Here, we hypothesise that this susceptibility to M. tuberculosis infection is linked to increased T regulatory (Treg) cells and Th2 cytokines in TB patients. To test this, we recruited 101 participants (71 TB patients, 12 non-TB pulmonary diseases and 18 healthy subjects) and investigated Treg cells and Th1/Th2 cytokines in peripheral blood. CD4(+)CD25(+) T cells and CD4(+)CD25(+)FoxP3(+) T cells significantly increased and IL-5 dramatically decreased in TB patients relative to healthy subjects. CD8(+)CD28(-) T cells, IFN-gamma, TNF-alpha, IL-10 and IL-4 significantly increased in patients with culture and sputum smear-positive pulmonary TB (PTB(+)) compared with healthy subjects. CD4(+)CD25(+)FoxP3(+) and CD8(+)CD28(-) T cells significantly decreased in PTB(+) after one month of chemotherapy. CD4(+), CD4(+)CD25(+) and CD8(+)CD28(+) T cells significantly increased in extra pulmonary TB patients after one month of chemotherapy. These findings suggest that M. tuberculosis infection induces circulating CD4(+)CD25(+)FoxP3(+) and CD8(+)CD28(-) T cell expansion, which may be related to the progression of M. tuberculosis infection, and that the balance between effector immune responses and suppression immune responses is essential to control M. tuberculosis infection. PMID- 20306326 TI - Photobiodegradation of phenol with ultraviolet irradiation of new ceramic biofilm carriers. AB - Activated sludge acclimated to biodegrade phenol was allowed to attach on and in light porous ceramic carriers and to function as a biofilm in a photolytic circulating-bed bioreactor (PCBBR). Phenol degradation in the PCBBR was investigated following three protocols: photolysis with ultraviolet light alone (P), biodegradation alone (B), and the two mechanisms operating simultaneously (P/B). Phenol was degraded at approximately equal rates by B and P/B, each of which was much faster than the rate by P. Furthermore, phenol was mineralized to a significantly greater extent with P/B than with either P or B. SEM showed that the biofilm survived well inside macropores that presumably shaded the microorganisms from UV irradiation, even though the UV light greatly reduced biofilm on outer surface of the carriers in the P/B experiments. Rapid biodegradation of phenol, enhanced mineralization, and survival of bacteria inside macropores demonstrated that being in a biofilm inside the porous carriers protected the bacteria from UV-light toxicity, allowing intimate coupling of photolysis and biodegradation. PMID- 20306327 TI - Where did all the pathological gamblers go? Gambling symptomatology and stage of change predict attrition in longitudinal research. AB - Attrition can introduce a systematic bias that can negatively affect validity (Cook and Campbell, Quasi-experimentation: design and analysis issues for field settings. Rand McNally, Chicago, 1979). Current longitudinal research in gambling, however, has generally overlooked the reasons for attrition. The current research examined the relationship between pathological gambling symptomatology, stage of change and attrition. Three hundred and seventy-nine participants were contacted 12 months after initially participating in a study on gambling for a follow-up session. Logistic regression revealed those in the contemplation and preparation stages of change reported higher levels of pathological gambling symptomatology and were more likely to drop out of the study compared to those in the precontemplation stage. As predicted, gambling symptomatology mediated the relationship between stages of change and attrition. The implication for longitudinal research on gambling as well as extant findings that have used this methodological approach is discussed. PMID- 20306325 TI - The perpetual movements of anaphase. AB - One of the most extraordinary events in the lifetime of a cell is the coordinated separation of sister chromatids during cell division. This is truly the essence of the entire mitotic process and the reason for the most profound morphological changes in cytoskeleton and nuclear organization that a cell may ever experience. It all occurs within a very short time window known as "anaphase", as if the cell had spent the rest of its existence getting ready for this moment in an ultimate act of survival. And there is a good reason for this: no space for mistakes. Problems in the distribution of chromosomes during cell division have been correlated with aneuploidy, a common feature observed in cancers and several birth defects, and the main cause of spontaneous abortion in humans. In this paper, we critically review the mechanisms of anaphase chromosome motion that resisted the scrutiny of more than 100 years of research, as part of a tribute to the pioneering work of Miguel Mota. PMID- 20306328 TI - Thirty years of lottery public health research: methodological strategies and trends. AB - Cognitive measurement techniques, such as self-reports of behavior and reaction time measures, largely dominate the field of psychological research. It is uncommon for researchers to examine a phenomenon of interest by observing actual behavior within natural settings. To illustrate the existence of this methodological trend for gambling research, this article reviews systematically selected samples of the peer-reviewed literature related to lottery gambling in general and the literature related to pathological gambling and lottery more specifically. The results indicate that self-report surveys dominate the extant lottery literature, and experimental investigations of video lottery terminal gambling supplement those papers. This landscape encourages researchers to expand their methodological approaches to the study of lottery gambling. Currently, we know more about what research participants tell us they do with respect to lottery gambling than we do about their real-life lottery gambling behavior. PMID- 20306329 TI - Family history and lung cancer risk: international multicentre case-control study in Eastern and Central Europe and meta-analyses. AB - Lung cancer is the most common neoplastic disease in Eastern and Central Europe. The role of hereditary factors in lung carcinogenesis is not fully understood. Family history (FH) of lung cancer and other tobacco-related cancers might be a strong predictor of the lung cancer risk. We investigated family history of cancer among first-degree relatives of 2,861 patients with lung cancer and 3,118 controls from the Czech Republic, Hungary, Poland, Romania, Russia, Slovakia, and United Kingdom within the IARC Multicenter Case-Control Study. Odds ratios (ORs) and 95% CI were calculated using logistic regression, adjusting for age, gender, study center, education, tobacco smoking, and number of first-degree relatives. In addition, we conducted a meta-analysis of 41 studies on FH of cancer and lung cancer risk. Positive FH of lung cancer increased risk of lung cancer with OR of 1.63 (95%CI: 1.31-2.01), and having two or more affected relatives with lung cancer further increased the risk of lung cancer with OR 3.60 (95%CI: 1.56-8.31). Among subjects aged less than 50, the OR for FH of lung cancer was 2.08 (95%CI: 1.18-3.63). The associations were generally stronger for squamous cell carcinoma and large cell carcinoma subtypes. Heterogeneity in results was not found with respect to smoking status and gender. A significant association was not observed for FH of other smoking-related tumors. The results of meta-analysis were consistent with that of our study with regard to young onset, non-smokers and histology. FH of lung cancer is a predictor of an increased risk of lung cancer, especially in subjects aged less than 50. PMID- 20306330 TI - Assessment of enzymatic efficiency on protein digestion in the tilapia Oreochromis niloticus. AB - The present study develops an experimental procedure aimed to estimate the efficiency of protein digestion in fish by measuring both gut transit rate and total amount of the main intestinal proteases (trypsin and chymotrypsin). The selected species was the Nile tilapia (Oreochromis niloticus). Total time for digestion, calculated through the estimation of gut transit rate using differently colored feeds, was 7.15 h. Mean production of trypsin and chymotrypsin was 15.94 and 24.11 mU in the proximal intestine and much lower (2,39, 4.90 mU) in the distal intestine. The enzyme efficiency, calculated from the average enzyme activity and time of residence of the digesta in each intestinal section, points to the major role of proximal intestine in protein digestion for this species. Results are discussed in relation to the main features characterizing digestion in stomachless fish. PMID- 20306331 TI - The association of inflammatory bowel disease and Mediterranean fever gene (MEFV) mutations in Turkish children. AB - BACKGROUND AND AIMS: Familial Mediterranean fever (FMF) and inflammatory bowel disease (IBD) concordance has been investigated in a few studies. We investigated MEFV mutations and prevalence of FMF disease in Turkish children with IBD and their relationship with the disease severity. METHODS: Sixteen patients with ulcerative colitis (UC), 14 with Crohn's disease (CD) and three with indeterminate colitis (IC) were enrolled in the study (median age 13 years, range 0.6-16 years, n = 19 boys). Demographic, clinical and laboratory characteristics of the patients were evaluated as well as the parameters of disease severity. All patients were screened for 12 common MEFV mutations. RESULTS: MEFV mutations were detected in 17 of 66 (25.7%) alleles. Seven patients (four patients with CD, two with IC, and one with UC) were also diagnosed as FMF. FMF disease was found in seven of all IBD patients (21.2%) and four of them had CD. M694V was the leading mutation, and as a disease-causing mutation, it was found to be significantly more frequent in CD patients than UC patients (Fisher's exact test P = 0.03). Demographics, laboratory evaluations, growth parameters, extraintestinal manifestations, and treatment with immunosuppressive agents other than steroids were comparable between the patients with and without FMF in most aspects. CONCLUSIONS: Although this is a small cohort, disease-causing MEFV mutations and FMF disease rate were increased among our patients with IBD. The increase was prominent among CD patients, whereas in UC the rate was similar to the Turkish healthy control population. PMID- 20306332 TI - The development of a clinical outcomes survey research application: Assessment Center. AB - INTRODUCTION: The National Institutes of Health sponsored Patient-Reported Outcome Measurement Information System (PROMIS) aimed to create item banks and computerized adaptive tests (CATs) across multiple domains for individuals with a range of chronic diseases. PURPOSE: Web-based software was created to enable a researcher to create study-specific Websites that could administer PROMIS CATs and other instruments to research participants or clinical samples. This paper outlines the process used to develop a user-friendly, free, Web-based resource (Assessment Center) for storage, retrieval, organization, sharing, and administration of patient-reported outcomes (PRO) instruments. METHODS: Joint Application Design (JAD) sessions were conducted with representatives from numerous institutions in order to supply a general wish list of features. Use Cases were then written to ensure that end user expectations matched programmer specifications. Program development included daily programmer "scrum" sessions, weekly Usability Acceptability Testing (UAT) and continuous Quality Assurance (QA) activities pre- and post-release. RESULTS: Assessment Center includes features that promote instrument development including item histories, data management, and storage of statistical analysis results. CONCLUSIONS: This case study of software development highlights the collection and incorporation of user input throughout the development process. Potential future applications of Assessment Center in clinical research are discussed. PMID- 20306333 TI - Fatal hemorrhage following trans--sphenoidal resection of a pituitary adenoma: a case report and review of the literature. AB - A 58-year-old woman with acromegaly developed massive epistaxis 7 days following trans-sphenoidal resection of a growth hormone-secreting pituitary adenoma. At autopsy, it was determined that the source of the hemorrhage was a rupture of the intracavernous segment of the internal carotid artery secondary to a bacterial arteritis. We describe the gross dissection and histologic examination undertaken in this unusual case, discuss the possible etiology of the infection and review the potential complications of this surgical approach with a view to improving forensic examination of these patients. PMID- 20306334 TI - [Is oral rehydration with nasogastric tube more efficient than rehydration with spoon? Preliminary study in children with non-severe dehydration in Joseph-Raseta Befelatanana Hospital, Madagascar]. AB - Since its recommendation by WHO, Oral Rehydration Solutions (ORS) contributed in reducing the rate of mortality due to acute gastroenteritis. In Madagascar, the rate of lethality imputed to gastroenteritis is about 3%. Rehydration can be performed either by using spoons which reliability is unsure because of parents' potential inobservance and child's refusal, or by nasogastric tube. The nasogastric tube may resolve these obstacles at the hospital. We realized a preliminary study to evaluate the efficacy and the safety of nasogastric tube and spoon administration of the ORS in rehydration of child with moderate post gastroenteritis dehydration. This is an open comparative study realized in the Pediatric Unit at the Joseph-Raseta-Befelatanana Hospital from the 21 January to 21 May 2008. Main outcomes was the proportion of rehydrated children at 4 hours, other were: failure at 8 hours, duration and volume of SRO, side effects. Fifty three children from 4-month to 4-year old among 1306 patients were recruited and forty-seven patients were included. Nine patients failed (4 children received ORS by spoon and 5 children by nasogastric tube). The use of spoon was more effective: 62.5% of the patients were rehydrated at the fourth hour versus 39.3% in nasogastric tube group (P = 0.04). Making debit constant presents difficulties in rehydration with nasogastric tube (44.4 %). Tolerance of nasogastric tube is generally good but 16.7% children get out their tube during this study. No ORS' inhalation was observed with both routes. No false passage or tube or ORS rejection was recorded in both techniques. This study shows that using spoon to rehydrate is more effective for the rehydration of moderate dehydration. The use of nasogastric tube needs more surveillance. PMID- 20306335 TI - [Mother's educational level and children's illness severity in the emergency unit of Joseph-Raseta-Befelatanana Hospital. What kind of implications]. AB - The parents 'educational conditions are one of the factors of health inequalities among children. During May 2009, the parents' instruction level of children admitted at the triage unit of a Pediatric Service in Antananarivo, Madagascar was evaluated and related to the severity of their children' health status and to the mode of reference. All the surviving children (from 2 months to 15 years old) were included in this study. Patients were classified by the IMCI guideline and we analyzed the educational level of their mothers. Each patient was classified as severe illness or without severe illness, according to IMCI algorithm. The quality of referring physician was recorded: public physicians, liberal physicians, nurses, or without referral. Among 296 children, 9 (3%) died before admission, 217 (75.6%) were included. Among them, 123 (56.7%) had a severe illness and 38,2% general signs of danger. The severity (92.3 versus 54.4%; P = 0.003), the number of severe dehydration (15.4 versus 3.9%; P = 0,027) and malnutrition (15.4 versus 4.4%; P = 0.039) were related with a poor parents educational level. The referral agents were mostly liberal physicians (56.7%), public physicians (26.7%) or nurses (1.8%). Mothers with higher educational level preferred to attend liberal physicians (58 versus 41.9%; P = 0.1). The reference delay was shorter if there was a severe illness (6.41 versus 19.6 days; P < 0.000) or no medical referral (51.1 versus 24.4%; P > 0.000). Despite the fact that access to hospital care was respectful of a two-step process (85.3%), the number of patients with severe illness was high among families with low educational level. Theses results suggest to educate in priority the mother with low education, in order to recognize the general signs of danger and facilitate early first health care. PMID- 20306337 TI - The impact factor ranking--a challenge for scientists and publishers. AB - INTRODUCTION: The Impact Factor (IF) has originally been designed as a bibliometric tool to estimate the relevance of a scientific journal and has as such gained widespread acceptance in the scientific community. It denominates the ratio of all citations received by a particular journal within 1 year and all original research or review articles published by that journal during the preceding 2 years. DISCUSSION: Recently, the IF is more and more frequently used to judge the importance of single articles or the scientific achievement of researchers themselves. These approaches are associated with a number of backlashes such as the inability of the IF to reflect citation rates of single articles, the lack of elimination of self-citations and the time frame within which the IF is calculated (i.e., the two preceding years). Thus, for the evaluation of single articles, citation rankings would be-though time consuming in their compilation-more adequate. For the assessment of the scientific output of individual researchers, the h-index is emerging as a valuable tool which reflects both the citation rate as well as the number of publications of a given researcher. CONCLUSION: Although the IF is suitable for judging the overall importance of journals, IF rankings should be made solely within the respective subspecialty categorizations to avoid overrepresentation of larger research areas. In conclusion, the IF remains the widest accepted qualitative tool for the benchmarking of journals, though the assessment of individual scientific quality remains a challenging endeavor. PMID- 20306336 TI - Heme oxygenase-1 gene delivery by Sleeping Beauty inhibits vascular stasis in a murine model of sickle cell disease. AB - Increases in heme oxygenase-1 (HO-1) and administration of heme degradation products CO and biliverdin inhibit vascular inflammation and vasoocclusion in mouse models of sickle cell disease (SCD). In this study, an albumin (alb) promoter-driven Sleeping Beauty (SB) transposase plasmid with a wild-type rat hmox-1 (wt-HO-1) transposable element was delivered by hydrodynamic tail vein injections to SCD mice. Eight weeks after injection, SCD mice had three- to five fold increases in HO-1 activity and protein expression in liver, similar to hemin treated mice. Immunohistochemistry demonstrated increased perinuclear HO-1 staining in hepatocytes. Messenger RNA transcription of the hmox-1 transgene in liver was confirmed by quantitative real-time polymerase chain reaction restriction fragment length polymorphism (qRT-PCR RFLP) with no detectible transgene expression in other organs. The livers of all HO-1 overexpressing mice had activation of nuclear phospho-p38 mitogen-activated protein kinase (MAPK) and phospho-Akt, decreased nuclear expression of nuclear factor-kappa B (NF-kappaB) p65, and decreased soluble vascular cell adhesion molecule-1 (sVCAM-1) in serum. Hypoxia-induced stasis, a characteristic of SCD, but not normal mice, was inhibited in dorsal skin fold chambers in wt-HO-1 SCD mice despite the absence of hmox-1 transgene expression in the skin suggesting distal effects of HO activity on the vasculature. No protective effects were seen in SCD mice injected with nonsense (ns-) rat hmox-1 that encodes carboxy-truncated HO-1 with little or no enzyme activity. We speculate that HO-1 gene delivery to the liver is beneficial in SCD mice by degrading pro-oxidative heme, releasing anti-inflammatory heme degradation products CO and biliverdin/bilirubin into circulation, activating cytoprotective pathways and inhibiting vascular stasis at sites distal to transgene expression. PMID- 20306338 TI - Variations of endonasal anatomy: relevance for the endoscopic endonasal transsphenoidal approach. AB - BACKGROUND: The endoscopic endonasal transsphenoidal approach (EETA) to the pituitary is performed by ear, nose, and throat (ENT) surgeons in collaboration with neurosurgeons but also by neurosurgeons alone even though neurosurgeons have not been trained in rhinological surgery. PURPOSE: To register the frequency of endonasal anatomical variations and to evaluate whether these variations hinder the progress of EETA and require extra rhinological surgical skills. METHODS: A prospective cohort study of 185 consecutive patients receiving an EETA through a binostril approach was performed. All anatomical endonasal variations were noted and the relevance for the progress of surgery evaluated. RESULTS: In 48% of patients, anatomical variations were recognized, the majority of which were spinae septi and septum deviations. In 5% of patients, the planned binostril approach had to be converted into a mononostril approach; whereas in 18% of patients with an anatomical variation, a correction had to be performed. There was no difference between the ENT surgeon and the neurosurgeon performing the approach. Complications related to the endonasal phase of the surgery occurred in 3.8%. Fluoroscopy or electromagnetic navigation has been used during 6.5% of the surgeries. CONCLUSION: Although endonasal anatomical variations are frequent, they do not pose a relevant obstacle for EETA. PMID- 20306339 TI - Thymidylate synthase (TYMS) enhancer region genotype-directed phase II trial of oral capecitabine for 2nd line treatment of advanced pancreatic cancer. AB - PURPOSE: The primary aim of this study was to characterize the 6-month overall survival and toxicity associated with second-line capecitabine treatment of advanced pancreatic cancer patients harboring the TYMS *2/*2 allele. The secondary aim was to analyze the response rate and pharmacokinetics of capecitabine-based therapy in this patient population. Lastly, TYMS, ATM and RecQ1 single nucleotide polymorphism were analyzed relative to overall survival in patients screened for study participation. METHODS: Eighty patients with stage IV pancreatic cancer were screened for the *2/*2 TYMS allele. Patients with the *2/*2 TYMS polymorphism were treated with capecitabine, 1,000 mg/m2 twice daily for 14 consecutive days of a 21 day cycle. Screened patients not possessing TYMS *2/*2 were monitored for survival. Pharmacokinetic analysis was done during Cycle 1 of the therapy. RESULTS: Sixteen of the 80 screened patients tested positive for *2/*2 TYMS variant. Four out of the 16 eligible patients were treated on study. The study was terminated early due to poor accrual and increased toxicity. Three patients experienced grade 3 non-hematologic toxicities of palmer-plantar erythrodysesthesia, diarrhea, nausea and vomiting. Grade 2 toxicities were similar and occurred in all patients. Only one patient was evaluable for response after completion of three cycles of therapy. The presence of the *2/*2 TYMS genotype in all of the screened patients trended toward a decreased overall survival. CONCLUSION: To our knowledge, this study represents the first genotype directed clinical trial for patients with pancreatic adenocarcinoma. Although the study was closed early, it appears capecitabine therapy in pancreatic cancer patients harboring the TYMS *2/*2 variant may be associated with increased non hematologic toxicity. This study also demonstrates the challenges performing a genotype-directed study in the second-line setting for patients with advanced pancreatic cancer. PMID- 20306341 TI - Influence of anthropogenic transformations of river bed on plant and macrozoobenthos communities. AB - This study describes the influence of urban area on plant communities and benthic invertebrates inhabiting the Slupia River (northern Poland). Ten plant communities and 37 macrozoobenthos taxa were determined during four seasonal samplings at 25 sampling sites (October 2005 and January, April, and August 2006). The obtained data set was statistically evaluated in order to reveal the influence of anthropogenic transformations on the investigated communities against the background of other abiotic factors. Multivariate regression tree (MRT) method was used for vegetation, while for benthic fauna, both MRT and artificial neural network (ANN) methods were applied. The following explanatory variables were used: season, water temperature, and salinity; location of a sampling site; degree of human impact on the riverbed; microhabitat; and substrate type. MRT analyses showed significant differences in plant community structure depending on the location of a sampling site, indicating the influence of anthropogenic pressure, while macrozoobenthos composition differed significantly only between seasons. The overall ANN model proved the importance of type and location of a sampling site for the approximation of benthic fauna density. Additionally, influence of the explanatory variables on the consecutive macrozoobenthos taxa was analyzed on the basis of separate ANN. PMID- 20306340 TI - Bioaccumulation of organochlorine pesticides in aquatic system--an overview. AB - In recent years, various environmental issues have aroused a concern on the pollution of pesticides in rivers and in their various intercompartments. Multiple residues of pesticides discharged from industries or as a result of extensive use of agrochemicals in agriculture have been monitored. These pesticide residues contaminate the river ecosystem and its intercompartments such as sediments, and aquatic biota, and make it harmful to humans when they contaminate food and drinking water. The pesticide contamination in water, sediments, and aquatic biota has been reported to be beyond the acceptable range. The most commonly found pesticides are organochlorine, namely, dichlorodiphenyltrichloroethane, hexachlorocyclohexane, endosulfan, heptachlor, lindane, dieldrin, aldrin, endrin, and others. The paper discusses the general description, classification, and toxicity of pesticides; it also aims to create public awareness among people and appraise them with various alternate methods to combat the problem of pesticide contamination. An attempt has also been made to elucidate the findings of various works on pesticides in aquatic system and to highlight the challenging aspects of pesticide contamination, which have not attracted the attention of investigators yet. PMID- 20306342 TI - A potent mitogenic lectin from the mycelia of a phytopathogenic fungus, Rhizoctonia bataticola, with complex sugar specificity and cytotoxic effect on human ovarian cancer cells. AB - A lectin with strong mitogenic activity towards human peripheral blood mononuclear cells (PBMCs) and cytotoxic effect on human ovarian cancer cells has been purified from the mycelium of a phytopathogenic fungus, Rhizoctonia bataticola, using ion exchange chromatography and affinity chromatography on asialofetuin-Sepharose. The lectin, termed RBL, is a tetramer of 11-kDa subunits and has unique amino acid sequence at its blocked N-terminus. The purified RBL was blood group nonspecific and its hemagglutination activity was inhibited by mucin (porcine stomach), fetuin (fetal calf serum) and asialofetuin. Glycan array analysis revealed high affinity binding of RBL towards N-glycans and also the glycoproteins containing complex N-glycan chains. Interestingly, the lectin showed high affinity for glycans which are part of ovarian cancer marker CA125, a high molecular weight mucin containing high mannose and complex bisecting type N linked glycans as well core 1 and 2 type O-glycans. RBL bound to human PBMCs eliciting strong mitogenic response, which could be blocked by mucin, fetuin and asialofetuin demonstrating the carbohydrate-mediated interaction with the cells. Analysis of the kinetics of binding of RBL to PBMCs revealed a delayed mitogenic response indicating a different signaling pathway compared to phytohemagglutinin L. RBL had a significant cytotoxic effect on human ovarian cancer cell line, PA 1. PMID- 20306343 TI - Molecular characterization of pig alpha2,3-Gal-beta1,3-GalNAc-alpha2,6 sialyltransferase (pST6GalNAc IV) gene specific for Neu5Acalpha2-3Galbeta1 3GalNAc trisaccharide structure. AB - Sialic acids of glycoconjugates play crucial roles in various biological processes, such as cell-cell communication and cell-substrate interaction. A sisalyltransferase, ST6GalNAc IV (Neu5Ac-alpha2,3-Gal-beta1,3-GalNAc-alpha2,6 sialyltransferase), catalyzes the formation of alpha2-6-linkages onto GalNAc residues of O-glycosidically linked Ser/Thr of proteins. In this study, we cloned the pig ST6GalNAc IV (pST6GalNAc IV) and investigated its functional characterization. pST6GalNAc IV cDNA has been isolated from pig liver tissues and it contains an entire open reading frame (ORF, 906 bp) coding for 302 amino acid residues. Entire ORF of pST6GalNAc IV containing sialylmotif 'L'-(Large), 'S' (Small) and '-VS' (Very small) has a high degree of sequence similarity with Homo sapiens (90%), Pan troglodytes (91%) and Mus musculus (87%). Expression of pST6GalNAc IV mRNA in various pig tissues was identified by reverse transcription polymerase chain reaction (RT-PCR) analysis. pST6GalNAc IV mRNA was highly expressed in tongue, muscle and heart, whereas it was not expressed in pancreas. For functional characterization of pST6GalNAc IV gene in pig kidney PK15 cells, we have also established pST6GalNAc IV-transfected PK15 cells, which are stably expressing the pST6GalNAc IV gene. The glycosylation pattern of pST6GalNAc IV transfected PK15 cells was detected by flow cytometry and immunofluorescence analysis with Maackia amurensis agglutinin (MAA), Maackia amurensis hemagglutinin (MAL II), Sambucus nigra agglutinin (SNA) and peanut agglutinin (PNA) lectins. The specific carbohydrate structures of Neu5Acalpha2-3Galbeta1-3(Neu5Acalpha2 6)GalNAc tetrasaccharide or Neu5Acalpha2-6GalNAc disaccharide recognized by MAL II and SNA were revealed to be newly synthesized by pST6GalNAc IV. From the results, it was suggested that the pig pST6GalNAc IV gene is capable of synthesizing Neu5Acalpha2-3Galbeta1-3(Neu5Acalpha2-6)GalNAc tetrasaccharide structures on O-glycoproteins. PMID- 20306344 TI - The machine paradigm and alternative approaches in cognitive science. AB - In a recent paper called To think human out of the machine paradigm, it is stated that psychological science operates within a machine paradigm that is committed to mechanical causality. In addition, it is emphasizes the epistemological and methodological limitations of explanations based in deterministic mechanics and instead argues for the need of an 'organic paradigm' that takes into consideration psychological processes such as subjectivity, inter-subjectivity, and agency. Although there is no doubt that much psychological science has operated under a machine paradigm, we argue that recent psychological research is pursued using a wide variety of approaches and with an absence of a partially integrated meta-theoretical corpus. The present situation looks more like a Tower of Babel of epistemological approaches and empirical programs. The reconsideration of the organic paradigm and an explicitly addressed epistemological framework could constitute a step forward and lead to an explanatory pluralism built on greater dialogue within the psychological sciences. PMID- 20306346 TI - Cutaneous and gastrointestinal pythiosis in a dog in Brazil. AB - The oomycete Pythium insidiosum is the pathogenic cause of pythiosis, a life threatening disease that affects several animal species. Canines are the second most affected species, and the disease is characterized by the development of cutaneous and gastrointestinal lesions. While concomitant cutaneous and gastrointestinal lesions are rarely found in the same animal, this report documents a case of concurrent cutaneous and gastrointestinal pythiosis in an 18 month-old female Labrador. This dog had an ulcerative cutaneous lesion on the right thoracic region for 12 months that was unresponsive to itraconazole and terbinafine therapy. Two months prior to death and concurrent with the cutaneous lesion, the dog became anorexic with frequent vomiting and bloody stools. At necropsy, a cutaneous lesion that extended subcutaneously into the intercostal muscles was observed. Additionally, the large intestine contained two lesions that caused luminal narrowing. Organs were collected, routinely processed and stained using hematoxylin and eosin and Gomori methenamine silver. Histological examination of the lesions in the large intestine and on the skin revealed areas of necrosis surrounded by a pyogranulomatous infiltrate. Occasionally, black, septate, branching hyphae were detected following staining with Gomori methenamine silver. The diagnosis of pythiosis was confirmed using immunohistochemical methods. This report describes the occurrence of concomitant gastrointestinal and cutaneous lesions in a dog and highlights the therapeutic difficulties encountered with this disease. PMID- 20306345 TI - Cysteine S-conjugate beta-lyases: important roles in the metabolism of naturally occurring sulfur and selenium-containing compounds, xenobiotics and anticancer agents. AB - Cysteine S-conjugate beta-lyases are pyridoxal 5'-phosphate-containing enzymes that catalyze beta-elimination reactions with cysteine S-conjugates that possess a good leaving group in the beta-position. The end products are aminoacrylate and a sulfur-containing fragment. The aminoacrylate tautomerizes and hydrolyzes to pyruvate and ammonia. The mammalian cysteine S-conjugate beta-lyases thus far identified are enzymes involved in amino acid metabolism that catalyze beta-lyase reactions as non-physiological side reactions. Most are aminotransferases. In some cases the lyase is inactivated by reaction products. The cysteine S conjugate beta-lyases are of much interest to toxicologists because they play an important key role in the bioactivation (toxication) of halogenated alkenes, some of which are produced on an industrial scale and are environmental contaminants. The cysteine S-conjugate beta-lyases have been reviewed in this journal previously (Cooper and Pinto in Amino Acids 30:1-15, 2006). Here, we focus on more recent findings regarding: (1) the identification of enzymes associated with high-M(r) cysteine S-conjugate beta-lyases in the cytosolic and mitochondrial fractions of rat liver and kidney; (2) the mechanism of syncatalytic inactivation of rat liver mitochondrial aspartate aminotransferase by the nephrotoxic beta lyase substrate S-(1,1,2,2-tetrafluoroethyl)-L-cysteine (the cysteine S-conjugate of tetrafluoroethylene); (3) toxicant channeling of reactive fragments from the active site of mitochondrial aspartate aminotransferase to susceptible proteins in the mitochondria; (4) the involvement of cysteine S-conjugate beta-lyases in the metabolism/bioactivation of drugs and natural products; and (5) the role of cysteine S-conjugate beta-lyases in the metabolism of selenocysteine Se conjugates. This review emphasizes the fact that the cysteine S-conjugate beta lyases are biologically more important than hitherto appreciated. PMID- 20306347 TI - Comparison of invasive and non-invasive blood pressure monitoring during clinical anaesthesia in dogs. AB - Monitoring blood pressure during anaesthesia is widely recommended in man and animals. The accuracy of any device used to measure blood pressure is an important consideration when selecting monitoring equipment, the ANSI/AAMI SP10 standard is widely cited in this respect in recent veterinary publications. Blood pressure was monitored using invasive and non-invasive techniques during clinical anaesthesia in 19 dogs. The results were compared using Bland-Altman analysis. The bias (and limits of agreement) between invasive and non-invasive measurement was 7.1 mmHg (+/-34.7) for systolic blood pressure, -1.8 mmHg (+/-27.4) for mean blood pressure and 6.9 mmHg (+/-27.5) for diastolic blood pressure. In a clinical setting the bias between invasive and non-invasive measurement techniques was similar or smaller than laboratory reports, however the limits of agreement were considerably wider suggesting that care should be exercised when interpreting NIBP values. PMID- 20306348 TI - A theoretical comparison of the models of prevention of research misconduct. AB - The current methods of dealing with research misconduct involve detection and rectification after the incident has already occurred. This method of monitoring scientific integrity exerts considerable negative effects on the concerned persons and is also wasteful of time and resources. Time has arrived for research administrators to focus seriously on prevention of misconduct. In this article, preventive models suggested earlier by Weed and Reason have been combined to arrive at six models of prevention. This is an effort to streamline the thinking regarding misconduct prevention, so that the advantages and disadvantages of each can be weighed and the method most appropriate for the institute chosen. PMID- 20306349 TI - Disclosure of unknown harms in magnetic resonance imaging research. AB - Unknown harms are by their nature difficult to communicate. While magnetic resonance imaging (MRI) has known risks (e.g., metal projectiles, dislodgement of medical implants), this imaging modality also has potential unknown long-term negative health effects associated with its static magnetic fields. We carried out a research ethics board (REB) file review of previously approved MRI research studies and found that unknown risks were either left undisclosed or were inadequately disclosed to research participants and REBs. This article outlines issues raised by our REB file review and suggests steps that should be taken in order to satisfactorily communicate information about potential unknown harms of MRI. PMID- 20306350 TI - Research misconduct policies of social science journals and impact factor. AB - In this study we gathered data on the misconduct policies of social science journals and combined it with the data from our previous study on journal misconduct policies, which did not include enough social science journals for data analysis. Consistent with our earlier finding, impact factor of the journal was the only variable significantly associated with whether a journal had a formal (written) misconduct policy with an odds-ratio of 1.72 (p < 0.01). We did not find that type of science (physical, biomedical, or social) or publisher had a significant effect on whether a journal had a policy. Another important finding is that less than half of the journals that responded to the survey had a formal misconduct policy. PMID- 20306351 TI - Dr. Cezanne and the art of re(peat)search: competing interests and obligations in clinical research. AB - Clinician researchers have a number of roles, each of which carries specific obligations. There are times when these obligations may be in competition (up to and including conflict) with each other. Using a narrative case study that describes a group of colleagues discussing their clinical department's participation in an industry-sponsored research protocol, we illustrate a number of the obligations faced by clinician researchers, and discuss how competing interests and obligations can lead to ethical problems. The case study is followed by a discussion of the effect of university-industry relations on competing interests and obligations in both clinical research and the role of the university, and a suggested framework that could be used to determine when university involvement in commercial research is ethically acceptable. PMID- 20306352 TI - Unethical research and the C.I.A. Inspector General Report of 2004: observations implicit in terms of the common rule. AB - Declassification of documents has given rise to the allegation that the Central Intelligence Agency may have conducted unethical research targeting detainee subjects. That allegation is examined using document analysis and the development of research goals and roles as defined in the Common Rule. This article sets aside issues as to whether enhanced interrogation techniques described in the declassified documents rise to legal definitions of torture. Instead, it presents a post hoc ethics review raising questions addressed by Institutional Review Boards recommending the filing of a for-cause noncompliance complaint with the Office for Human Research Protection against the Central Intelligence Agency. PMID- 20306353 TI - Influence of left versus right hemibody onset Parkinson's disease on cardiovascular control. AB - Whereas the left hemisphere is involved in regulating the parasympathetic nervous system, the right hemisphere regulates the sympathetic. Given the asymmetrical onset of motor symptoms and neuropathology in PD, differences in cardiovascular functions might be expected between PD patients with left hemibody onset (LHO) versus right hemibody onset (RHO). A total of 66 PD patients served as participants, including 31 LHO patients and 35 RHO PD patients. All participants had their resting heart rate (HR) and blood pressure (BP) recorded. Although the LHO group had lower systolic BP, it had higher resting HR than did the RHO group. The reason for this dissociation is not known but might be related to asymmetrical vagus nerve control of the heart (SA node). Future researchers might want to use additional indices of cardiovascular functioning that are more precise measures of parasympathetic and sympathetic functioning, as well as learn the influence of dopaminergic medications. PMID- 20306354 TI - Narrative therapy for adults with major depressive disorder: improved symptom and interpersonal outcomes. AB - This study investigated depressive symptom and interpersonal relatedness outcomes from eight sessions of manualized narrative therapy for 47 adults with major depressive disorder. Post-therapy, depressive symptom improvement (d=1.36) and proportions of clients achieving reliable improvement (74%), movement to the functional population (61%), and clinically significant improvement (53%) were comparable to benchmark research outcomes. Post-therapy interpersonal relatedness improvement (d=.62) was less substantial than for symptoms. Three-month follow-up found maintenance of symptom, but not interpersonal gains. Benchmarking and clinical significance analyses mitigated repeated measure design limitations, providing empirical evidence to support narrative therapy for adults with major depressive disorder. PMID- 20306355 TI - Meanings of home and mental well-being among Sudanese refugees in Canada. AB - OBJECTIVES: This article examines family and social factors that affect refugee mental health during resettlement by presenting qualitative analysis of the concept of home and its functional and psychological meanings based on findings from research with Sudanese refugees in Canada. DESIGN: Data were collected in two successive multi-method, community-based studies between 2003 and 2007 with Sudanese refugee participants in Ontario and Alberta, Canada. The first study used survey methods with 220 participants in seven sites and the second, in-depth qualitative interviews with 30 community members in three sites. RESULTS: In the first study, economic hardship and family adaptation challenges were reported to affect Sudanese mental well-being. The second study explored cultural aspects of Sudanese family and community well-being in greater depth. Meanings of home emerged from data as a key concept linking social support, resettlement, and mental health. Findings highlight how the presence or absence of the social supports associated with home affect refugees' mental health during resettlement. The analysis focuses on four themes: emotional support; fulfilling social roles and expectations; problem solving and conflict resolution; and dignity and growth, as well as perceived impact on community mental health. CONCLUSION: Qualities of home that Sudanese lack during resettlement points to critical gaps that must be filled by mental health and other service providers to promote positive refugee mental health in countries of resettlement. PMID- 20306356 TI - Awareness of executive functioning deficits in multiple sclerosis: self versus informant ratings of impairment. AB - This study investigates the accuracy of self and informant ratings of executive dysfunction in a multiple sclerosis (MS) and control sample. Participants completed a neuropsychological battery. Participants and informants completed depression measures and the Dysexecutive Questionnaire (DEX). MS participants rated themselves more impaired than controls, while informants' ratings were not statistically different. MS participants' performance on executive tasks was more highly correlated with self than informant DEX ratings. Discrepancies between informant DEX ratings and executive performance were related to executive functioning for the MS participants only. Overall, results indicate that MS patients were able to accurately rate their executive functioning. PMID- 20306357 TI - Do warnings deter rather than produce more sophisticated malingering? AB - Following Youngjohn, Lees-Haley, and Binder's (1999) comment on Johnson and Lesniak-Karpiak's (1997) study that warnings lead to more subtle malingering, researchers have sought to better understand warning effects. However, such studies have been largely atheoretical and may have confounded warning and coaching. This study examined the effect on malingering of a warning that was based on criminological-sociological concepts derived from the rational choice model of deterrence theory. A total of 78 participants were randomly assigned to a control group, an unwarned simulator group, or one of two warned simulator groups. The warning groups comprised low- and high-level conditions depending on warning intensity. Simulator participants received no coaching about how to fake tests. Outcome variables were scores derived from the Test of Memory Malingering and Wechsler Memory Scale-III. When the rate of malingering was compared across the four groups, a high-level warning effect was found such that warned participants were significantly less likely to exaggerate than unwarned simulators. In an exploratory follow-up analysis, the warned groups were divided into those who reported malingering and those who did not report malingering, and the performance of these groups was compared to that of unwarned simulators and controls. Using this approach, results showed that participants who were deterred from malingering by warning performed no worse than controls. However, on a small number of tests, self-reported malingerers in the low-level warning group appeared less impaired than unwarned simulators. This pattern was not observed in the high-level warning condition. Although cautious interpretation of findings is necessitated by the exploratory nature of some analyses, overall results suggest that using a carefully designed warning may be useful for reducing the rate of malingering. The combination of some noteworthy effect sizes, despite low power and the small size of some groups, suggests that further investigation of the effects of warnings needs to continue to determine their effect more fully. PMID- 20306358 TI - Evaluation of anti-fertility activity of Tabernaemontana divaricata (Linn) R.Br. leaves in rats. AB - The aim of the present study was to assess the anti-fertility activity of ethanolic extracts of Tabernaemontana divaricata (TD) leaves in oestrogenic activity models in immature female rats. Mature green leaves of TD were collected and authenticated. Extractions of the dried leaves were carried out with ethanol in a Soxhlet's apparatus. For oestrogenic activity, the extracts were administered orally once daily at a dose of 200 and 400 mg kg(-1), and the activity was compared with the standard drug ethinyl oestradiol (0.02 mg). The extracts caused significant increase in uterine weight compared to the control. The ethanolic extract exhibited oestrogenic activity. The histological study of epithelium tissues with the 400 mg of TD extract-treated animals showed increases in the height of the luminal epithelium and loose edematous stroma when compared with the 200 mg of TD extract-treated group of animals. However, this was better than the control group of animals. Enhanced uterine weight and increase in the height of luminal epithelium and histological characteristics suggest that TD extract may be useful in anti-fertility therapy. PMID- 20306359 TI - Two new compounds from Semen celosiae and their protective effects against CCl4 induced hepatotoxicity. AB - Two new oleanolic acid saponins, namely celosin A (1) and celosin B (2), together with six known compounds, stigmasterol, beta-sitosterol, beta-daucosterol, hexacosoic acid, palmitic acid and stearic acid, were isolated from the ethanolic extract of Semen celosiae. The structures of celosin A (1) and celosin B (2) were determined by spectral analysis (including 1D- and 2D-NMR). The hepatoprotective activity of 1 and 2 with oral doses 1.0, 2.0 and 4.0 mg kg-1 were investigated by carbon tetrachloride CCl4-induced hepatotoxicity in mice. The results indicate that they have significant hepatoprotective effects, and that these hepatoprotective effects may be due to the antioxidant capability. PMID- 20306360 TI - Secondary metabolites from Eryngium species. AB - From the seed and leaf extracts of Eryngium species, two new compounds were isolated, along with an aliphatic ketone and several known terpenoids reported from a member of Umbelliferae for the first time. Their structures were elucidated by chemical methods and spectroscopic analysis. PMID- 20306361 TI - Chemical constituents from the leaves of Michelia alba. AB - (-)-N-Formylanonaine (1), (-)-oliveroline (2), (+)-nornuciferine (3), lysicamine (4), (+)-cyperone (5), (+)-epi-yangambin (6), ficaprenol-10 (7), pheophytin a (8), aristophyll C (9) and michephyll A (10) were isolated from the leaves of Michelia alba DC (Magnoliaceae). Among them, 10 is a new compound. The structures of these compounds were characterised and identified by spectral analyses. We have also presented the antioxidation activity of 10. PMID- 20306362 TI - Nematicidal natural products from the aerial parts of Rubus niveus. AB - Studies on the aerial parts of Rubus niveus yielded six known compounds, 3,5 dihydroxy benzoic acid C(7)H(6)O(4), (1), gallic acid C(7)H(6)O(5) (2), ethyl galactoside (3), oleanolic acid (4), beta-sitosterol (5) and 3-O-[beta-D galactopyranosyl-(12)-D-glucopyranoside (6). Besides this, a gallic acid derivative with methyl substitution was synthesised as tetramethyl gallate (3). Together with this derivative, compounds 1, 2, the alcohol soluble, chloroform soluble and petroleum ether soluble extracts of the aerial parts of R. niveus were screened for its nematicidal activity against freshly hatched second stage juveniles of Meloidogyne incognita (root-knot nematode), exhibiting 100, 94, 100, 52, 45 and 14% mortality, respectively of M. incognita after 48 h at 0.5% concentration. Compounds 1, 2 and 3 were found to be more potent than the nematicide Azadirachta indica at the same concentration. Negative results were obtained for nematicidal activity of the petroleum ether extract of R. niveus leaf extract. This is the first report on the isolation of chemical constituents as well as the nematicidal activity of compounds and any part of R. niveus. PMID- 20306363 TI - Production of cycloartane triterpene glycosides in shoot cultures of Astragalus sieberi DC. AB - Shoot tips of the germinated seeds of Astragalus sieberi DC. were cultured on MS medium supplemented with 0.1 mg L(-1) each of naphthalene acetic acid (NAA) and benzyl adenine (BA) for establishment of shoot cultures. The effect of different concentrations of growth regulators on saponin content was studied and optimised. Saponin content was monitored by HPLC analysis. The most appropriate growth regulator with which to produce the highest content of saponins in shoot cultures was 0.5 mg L(-1) each of NAA and BA. The isolated cycloastragenol-3-O-glucoside was identified by spectral analysis and compared with an authentic sample. PMID- 20306364 TI - A novel sesquiterpenoid from the roots of Cinnamomum subavenium. AB - Subamol (1), a novel Cinnamomum sesquiterpenoid, has been isolated from Cinnamomum subavenium (Lauraceae), and its structure was determined on the basis of spectroscopic analysis. PMID- 20306365 TI - Synthesis of 1-octacosanol and GC-C-IRMS discrimination of samples from different origin. AB - Lately, long-chain primary alcohols have been investigated in depth on account of their biological activities. In particular, 1-octacosanol (C(28)H(57)OH), the main component of policosanol, the hypolipidaemic fatty alcohol mixture obtained from sugar cane wax, has been the subject of a multitude of pharmacological studies. The aim of this work was to search a convenient synthetic protocol for the preparation of 1-octacosanol in a gram scale. The key step was a Wittig reaction between the octadecyltriphenylphosphonium ylide and the methyl 10 oxodecanoate. Some steps were further improved by power ultrasound and microwave irradiation, either alone or in combination. Our methodology is suitable for a rapid generation of homologues by varying the chain length in the alkyl halide. Due to the high commercial value, a series of 1-octacosanol samples, either isolated from natural sources or from synthesis (different origin and suppliers), were analysed by gas chromatography-combustion-isotopic ratio mass spectrometry (GC-C-IRMS) and according to the carbon isotopic content, classified on the basis of their origin. PMID- 20306366 TI - A short and facile synthesis of 2-(1Z)-(3-hydroxy-3,7-dimethylocta-1,6-dienyl) 1,4-benzenediol and 1-(3'-methoxypropanoyl)-2,4,5-trimethoxybenzene isolated from Cordia alliodora. AB - A novel synthesis of 2-(1Z)-(3-hydroxy-3,7-dimethylocta-1,6-dienyl)-1,4 benzenediol and 1-(3'-methoxypropanoyl)-2,4,5-trimethoxybenzene has been carried out by making use of an easily available starting material, acceleration by MW irradiation and the use of water as a green solvent in the key steps. PMID- 20306367 TI - Chemical constituents of Sisymbrium irio L. from Jordan. AB - Investigation of the aerial parts of Sisymbrium irio L. (Cruciferea) collected in northern Jordan afforded two new compounds, sitosteryl-6'-O-undecanoate-beta-D glucoside (1) and (Z)-8,11,12-trihydroxyoctadec-9-enoic acid (2), in addition to 12 known compounds, 10 of which are reported for the first time from the plant. The structures of all of the compounds were established by spectroscopic and chemical methods. PMID- 20306368 TI - The chemical structures, plant origins, ethnobotany and biological activities of homoisoflavanones. AB - This work reviews the four basic structural types of homoisoflavanones. The relationships between the various structures of homoisoflavanones and their plant origins, ethnobotany and biological activities are put into perspective. PMID- 20306369 TI - Cognitive rehabilitation in posterior cortical atrophy. AB - Posterior cortical atrophy (PCA) is a rare early-onset dementing syndrome presenting with visuo-perceptual deficits. Clinicopathologically, it is most commonly considered a form of Alzheimer's disease. We present the case of a 64 year-old male patient with posterior cortical atrophy who took part in a cognitive rehabilitation programme that included psychoeducation, compensatory strategies, and cognitive exercises. After the cognitive rehabilitation programme, subtle differences were found in visuoperceptual tasks and in the patient's subjective perception of difficulties. Cognitive rehabilitation may temporarily improve functioning in patients with posterior cortical atrophy. PMID- 20306370 TI - Encoding and representation of simultaneous and sequential arrays in visuospatial working memory. AB - The effect of presentation type on organization in visuospatial working memory (VSWM) was examined. Stimuli were presented sequentially or simultaneously at study, and participants made same/different judgements at test. The test array varied in four different spatial configuration conditions: one featuring no changes from study, one in which two items switched, one in which the same array repeated but in a different location, and one in which a completely novel test stimulus appeared. Results indicated the use of a global configuration for both simultaneous and sequential presentations and showed increased impairment of item level knowledge with sequential presentations. Overall, these results support the use of a global configuration organization as a fundamental aspect of VSWM processing. PMID- 20306371 TI - Items on the left are better remembered. AB - Neurologically intact individuals show a spatial processing bias in perception tasks, specifically showing a bias towards the left in bisecting lines. We present evidence for a novel finding that a leftwards bias occurs in short-term memory for recently presented arbitrary bindings of visual features. Three experiments are reported, two of which involve a total of over 60,000 participants with a small number of trials for each. Experiment 3 involved a larger number of trials for each of 144 participants. Participants reproduced from immediate memory arrays of shape-colour-location bindings. In all three experiments, significantly more errors were observed in reproduction of items presented on the right of the array than on the left. Results could not be accounted for by perceptual errors, or by order of presentation or order of reproduction. Findings suggest that items presented on the left are better remembered, indicating a spatial asymmetry in forming or retrieving feature bindings in visual short-term memory. PMID- 20306373 TI - [The solidarity of the profession]. PMID- 20306374 TI - [Recognition for Prof. Dr. Dr. Alf Trojan on awarding of the Salomon-Neumann Medal of the German Society of Social Medicine and Prevention on 23 September 2009 in Hamburg]. PMID- 20306375 TI - [Solidarity in the course of society and health-care system]. PMID- 20306376 TI - [Personal responsibility for health. An interdisciplinary discussion on obesity as an example]. AB - Considering obesity as an example, the present study has developed an ethical, legal and psychological understanding of personal responsibility, which aims at enabling and activating health promoting behaviour. Enhancing individual capabilities and modifying social and political factors that have an effect on individual behaviour are highlighted as a promising, appropriate and ethically sound strategy of prevention. PMID- 20306377 TI - ["15 questions for..."]. PMID- 20306378 TI - [The future for CME articles]. PMID- 20306379 TI - Thoracic aortic aneurysms. PMID- 20306380 TI - Measurement of liver elasticity with acoustic radiation force impulse (ARFI) technology: an alternative noninvasive method for staging liver fibrosis in viral hepatitis. AB - PURPOSE: The acoustic radiation force impulse (ARFI) technology is a novel ultrasound method that provides information about the local elasticity of tissue in real-time. ARFI is integrated in a conventional ultrasound system. The aim of this exploratory study was to evaluate this new technique in the assessment of liver fibrosis in a cohort with chronic viral hepatitis B and C and to ascertain the most reliable hepatic segment for measurements. MATERIALS AND METHODS: 57 patients (27 female, 30 male, mean age 54 years) with chronic viral hepatitis B and C underwent ARFI imaging and consecutively liver biopsy. The results were compared to the histological fibrosis degree (F), which served as the reference. 20 healthy volunteers received ARFI quantification of different segments of the liver. RESULTS: The best ARFI assessments with the lowest rate of invalid measurements were carried out by an intercostal approach to segment VII/VIII of the liver. The ARFI velocities of the healthy group had a mean of 1.09 m/s (range 0.79 - 1.32 m/s), the means of the patient group ranged from 0.83 to 4.19 m/s. ARFI quantification correlated significantly with the histological fibrosis stage (p < 0.001). The area under the receiver operating characteristic (ROC) curves for the accuracy of ARFI imaging was 85 %, 92 % and 87 % for the diagnosis of moderate fibrosis (>or= F2), severe fibrosis (>or= F3) and cirrhosis ( = F 4), respectively. CONCLUSION: This study underscores the usefulness of ARFI as a quick method for assessing liver fibrosis or cirrhosis in patients with HBV or HCV. ARFI measurements of the liver should be performed via an intercostal access. Increasing ARFI velocities correlate with higher degree of hepatic fibrosis. PMID- 20306381 TI - [Classification of solid soft tissue tumours by ultrasonography]. AB - PURPOSE: Malignant soft tissue tumours appear infrequently in comparison to benign lesions. Clinical misdiagnosis leads to inadequate or delayed therapy in many cases of soft tissue sarcoma. The present study explores the question if ultrasonography as a widely-used diagnostic tool allows for a discrimination of benign and malignant soft tissue tumours. MATERIALS AND METHODS: In a prospective study over a period of 8 years 224 histologically ascertained solid soft tissue tumours, thereof 120 sarcomas and 27 aggressive benign lesions were investigated by B-mode and colour Doppler sonography. The echotexture was analysed computer based using the parameters echogenicity, homogeneity and vascularisation in all lesions. RESULTS: Different tumour groups showed typical patterns of echotexture, which enabled a classification using 6 categories, distinguishing homogenous hyperechoic, heavily inhomogeneous and homogenous hypoechoic lesions, each group linked to an elevated or low vascularisation. Implementation of the proposed classification revealed a sensitivity in the detection of soft tissue sarcomas and aggressive benign lesions of 94.4 % with a specificity of 79.7 % and an accuracy of 89.7 %. CONCLUSION: Ultrasonography allows for a determination of the diagnostic and therapeutic procedure in soft tissue tumours. Due to the fact that soft tissue sarcomas present hypervascularised almost exclusively, predominantly homogenous hypoechoic, rarely homogenous hyperechoic, and aggressive benign tumours present homogenous hypoechoic predominantly, such patterns require a biopsy prior to further surgical therapy. However, in homogenous hyperechoic lesions displaying a low blood flow either a primary resection or a conservative treatment with follow-up examinations can be discussed depending on clinical findings and history of the patient. Although the group of heavily inhomogeneous tumours within our collective consisted of benign lesions exclusively, biopsy should be recommended in theses cases in order to exclude a soft tissue sarcoma. PMID- 20306382 TI - Gastric pneumatosis in necrotizing enterocolitis. PMID- 20306383 TI - Considering laparoscopic salvage options--is pre-emptive omentectomy necessary in paediatric peritoneal patients? AB - BACKGROUND: In paediatric peritoneal dialysis patients, pre-emptive omentectomy is discussed controversially and literature provides only little data concerning this issue. Our aim was to evaluate the rate of omentum-majus-related problems in our patients, in whom omentectomy was generally not performed. Furthermore, we were interested in the success rates of laparoscopic adhesiolysis. PATIENTS AND METHODS: Between 09/2006 and 03/2008, we regularly saw 18 peritoneal dialysis patients in whom we retrospectively analysed medical records to determine the rate of catheter-related complications. In addition, we evaluated the success rates of laparoscopic adhesiolysis. RESULTS: During 355 dialysis months in 18 patients, we observed 7 omentum-majus-related obstructions in 6 patients (1/50.7 PM). The median age of the patients affected was 9 years, median filling volume at the time of the obstruction was 671 ml/m (2). Laparoscopic adhesiolysis was successful in 4 out of 7 episodes. In 3 cases, the catheter lumen was plugged by necrotic portions of the omentum and the catheters had to be replaced. CONCLUSION: Our data confirm omentum-majus-related catheter obstruction as a major cause of catheter dysfunction. However, in comparison to literature, it remains unclear to which extent omentectomy can reduce the incidence of catheter obstruction in general (including e. g. obstruction due to coagulation). Thus, the decision to perform an omentectomy should be taken individually after careful consideration. In case of omentum-majus-associated obstruction, early but not late laparoscopic intervention proved to be a successful, minimally invasive technique to restore catheter function. PMID- 20306385 TI - Accuracy of endoscopic ultrasound in preoperative staging of esophageal cancer: results from a referral center for early esophageal cancer. AB - BACKGROUND AND STUDY AIM: Endoscopic ultrasound (EUS) has been regarded as the most accurate staging tool in esophageal cancer. Staging results have a strong impact on the decision as to whether a patient should undergo endoscopic treatment, surgery alone, or neoadjuvant therapy. This retrospective study was conducted to analyze the accuracy of esophageal cancer staging using EUS. METHODS: All patients who received EUS for staging of esophageal cancer before esophagectomy from February 2003 to December 2007 at a high volume academic tertiary care center were included. RESULTS: 179 consecutive patients (mean age 64.4 +/- 9.5 years; 142 men) underwent esophageal resection for Barrett's adenocarcinoma (n = 134) and squamous cell cancer (n = 45). Postoperatively, 99 patients were staged as having T1 cancers (55 %), 30 patients T2 (17%), 46 patients T3 (26%), and four patients T4 (2%). The sensitivity and specificity of EUS relative to the T stage were 82% and 91%, respectively, for T1; 43% and 85% for T2; and 83% and 86% for T3. The overall accuracy for EUS in identifying the correct T stage was 74% (95%CI 66-80). Positive lymph nodes were diagnosed histologically in 68 patients (38%). The sensitivity, specificity and accuracy of EUS for the diagnosis of N1 were 71%, 74% and 73% (95%CI 65-79), respectively. CONCLUSIONS: The diagnostic accuracy of EUS in patients with esophageal cancer is still unsatisfactory. T2 cancers in particular are frequently overstaged, with a significant effect on the subsequent treatment strategy. PMID- 20306384 TI - Prospective comparison of endoscopic ultrasound-guided fine-needle aspiration and surgical histology in upper gastrointestinal submucosal tumors. AB - STUDY AIM: To assess the accuracy of ultrasound-guided fine-needle aspiration biopsy in the differential diagnosis of gastrointestinal stroma cell tumors (GIST) from other submucosal tumors, using both cytology and histology. PATIENTS AND METHODS: We conducted a prospective study from May 2005 to September 2008 in all patients presenting with upper gastrointestinal submucosal tumors. Only patients in whom surgical resection was carried out were included in the final analysis. In cases of mesenchymal tumor, immunocytochemistry was attempted for further differentiation between GIST and non-GIST. Surgical histopathology served as the gold standard. RESULTS: A total of 47 patients were analyzable, with a final histologic diagnosis of 35 mesenchymal tumors. Sufficient tissue for conventional cytologic diagnosis was obtained only in the 35 patients with mesenchymal tumors; in this subgroup, immunocytochemistry was possible in 46 %. If and only if enough material was available for immunocytochemistry, the sensitivity for (correct recognition of) GIST tumors was 93 %. In all 12 patients with nonmesenchymal tumors and lesions, cytology was nondiagnostic and the diagnosis had to be based on clinical suspicion and the appearance on endoscopy and endoscopic ultrasound (EUS). On an intention-to-diagnose basis, endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) had a positive predictive value for mesenchymal tumors of 100 %, but no value for the diagnosis of other lesions; using immunocytochemistry, a GIST tumor was recognized among the mesenchymal tumors with a sensitivity of 58 % and a specificity of 8 %. CONCLUSIONS: EUS-FNA-based cytology is safe and has only limited value for the differential diagnosis of submucosal tumors, mainly because insufficient material is harvested. Better tissue acquisition techniques are necessary for better differential diagnosis. PMID- 20306386 TI - Can early precut implementation reduce endoscopic retrograde cholangiopancreatography-related complication risk? Meta-analysis of randomized controlled trials. AB - BACKGROUND AND STUDY AIMS: Precut papillotomy is considered a risk factor for endoscopic retrograde cholangiopancreatography (ERCP)-related complications; however whether the complication risk is due to precut itself or to the prior prolonged attempts is still debated; therefore, early precut implementation has been suggested to reduce the complication rate. We conducted a meta-analysis of randomized controlled trials (RCTs) comparing cannulation and complication rates of early precut implementation with persistent attempts by the standard approach. METHODS: RCTs that compared cannulation and complication rates of the early precut implementation and of persistent attempts by the standard approach were included. Summary effect sizes were estimated by odds ratio (OR) with a random effects model and by Peto OR. RESULTS: Six RCTs with a total of 966 subjects met the inclusion criteria. Overall cannulation rates were 90 % in both randomization groups (OR 1.20; 95 % confidence interval [CI] 0.54 - 2.69). Post-ERCP pancreatitis developed in 2.5 % of patients randomized to the early precut groups and in 5.3 % of patients from the persistent attempts groups (OR 0.47; 95 %CI 0.24 - 0.91). The overall complication rates, considering pancreatitis, bleeding, cholangitis, and perforation rates, were 5.0 % in the early precut groups and 6.3 % in the persistent attempts groups (OR 0.78; 95 %CI 0.44 - 1.37). CONCLUSIONS: RCTs that investigated the issue of timing of the precut procedure were limited. Current evidence suggests that in experienced hands the early implementation of precut and persistent cannulation attempts have similar overall cannulation rates; early precut implementation reduces post-ERCP pancreatitis risk but not the overall complication rate. Further studies are needed to confirm these findings. PMID- 20306387 TI - [From the "oversupply of practical physicians" to the "mountain of hospital beds" -organised medical profession and junior staff having to face cost explosion]. AB - The catchwords "oversupply of physicians" and "mountain of hospital beds" may be considered to mark two points of culmination in German health policy discussion between 1960 and 1990. The political background and the practical implications of this discussion will be illustrated and appreciated taking into account both the distinct positions of the organised medical profession and junior staff. PMID- 20306388 TI - [Back pain, pain therapy and satisfaction with therapy--analyses in a cohort of elderly primary health care patients (getABI)]. AB - INTRODUCTION: Back pain can affect quality of life and independence of elderly people. The goal of this study was to determine the prevalence of back pain in a cohort of elderly primary health care patients, as well as to analyse pain therapy and level of satisfaction with therapy. METHODS: In a monitored prospective cohort study (German epidemiological trial on ankle brachial index, getABI), 6 880 unselected patients aged 65 years and above have been followed up by 344 representative primary care physicians in Germany since October 2001. In the 5-year follow-up, 2 120 patients (median age 76; 70-94 years; 53.7% women) were interviewed by telephone about location and intensity of pain during the past 3 months, about impairment due to pain, about pain therapy and satisfaction with therapy. RESULTS: Of the 2 095 patients who answered the questions on pain, 803 (38.3%) had suffered from pain of the upper and/or lower back within the past 3 months. The prevalence of back pain was higher in female than in male patients (45.0% vs. 30.6%; p<0.05). In about half of the men and half of the women with back pain, the back was also the main pain region. This subsample (n=409) with the back as main pain region (BMP) was analysed in more detail. The mean "von Korff intensity score" (scale 0-100) was 46.5+/-19.9, the mean "von Korff impairment score" (scale 0-100) was 23.6+/-23.0. Women reported a higher mean intensity of back pain than men (48.8+/-20.0 vs. 42.4+/-19.3; p<0.05) and complained about a higher pain-related impairment (26.2+/-23.5 vs. 19.2+/-21.5; p<0.05). Of all BMP patients, 253 (61.9%) visited a physician (at least once) during the past 3 months due to pain. The treatments most frequently applied (multiple answers permitted) were: oral medication (62.5%), injections (38.6%), and physiotherapy (35.9%). Patients (n=224) were asked to rate the therapy on a scale from 1 to 6 (1 being the highest grade). The mean rating was 3.1+/-1.4. 36.8% were not satisfied with pain relief. 61.4% wished for a considerable improvement of their pain therapy. CONCLUSION: The prevalence of back pain in elderly people is high and leads to functional limitations. As a consequence of the rather low mean satisfaction with pain therapy, future studies on back pain therapy should include an assessment of patient preferences and satisfaction with therapy. It remains questionable, if the current medical care for elderly people with back pain complies with the latest guidelines that demand for multimodal therapy. PMID- 20306389 TI - [Health from philosophical-anthropological and theological points of view--geared to an ideal of activity and performance? ]. AB - Today's understanding of what health or well-being means often refers to certain ideals of activity and achievement. Lennart Nordenfelt's concept of health will be used to analyse and discuss this phenomenon. Furthermore, using the example of the ecclesiastical paper "God is a friend of life", we will explore if such conceptions of health also affect the teachings of the Christian churches. PMID- 20306390 TI - Endoscopic detection of an early manifestation of EBV-related post-transplant lymphoproliferative disorder in a transplanted colon. PMID- 20306391 TI - Hepatobiliary fascioliasis treated at endoscopic retrograde cholangiopancreatography. PMID- 20306392 TI - Suppurative appendicitis at colonoscopy. PMID- 20306393 TI - Appendiceal mucocele in ulcerative colitis. PMID- 20306394 TI - Diagnosis of a small splenic artery aneurysm mimicking a gastric submucosal tumor on endoscopic ultrasound. PMID- 20306395 TI - Endoscopic intraluminal vacuum therapy of duodenal perforation. PMID- 20306396 TI - Weblike stenosis due to gastroesophageal reflux disease, treated with an insulation-tipped diathermic knife-2 (IT-2). PMID- 20306397 TI - Fatal venous air embolism during upper endoscopy in a patient with percutaneous transhepatic cholangiography (PTC) catheter. PMID- 20306398 TI - Intestinal endometriosis: an uncommon cause of rectal bleeding. PMID- 20306399 TI - Colitis cystica profunda presenting with a mucus pool within the stalk of a pedunculated colon polyp. PMID- 20306400 TI - Malposition of a percutaneous endoscopic gastrostomy tube in the jejunum. PMID- 20306401 TI - The cat scratch colon sign in a patient with chronic cholestasis. PMID- 20306402 TI - Splenic infarction after cyanoacrylate injection for fundal varices. PMID- 20306403 TI - Esophageal ulceration mimicking malignancy in a patient with severe kyphoscoliosis. PMID- 20306404 TI - Heterotopic pancreas: a difficult diagnosis. PMID- 20306405 TI - Extraction of a rectal foreign body using a custom-made giant snare. PMID- 20306406 TI - An unusual cause of upper gastrointestinal bleeding. PMID- 20306407 TI - Endoscopic retrograde cholangiopancreatography in situs inversus partialis. PMID- 20306408 TI - Denudation of the esophageal mucosa following ingestion of a foreign body and vinegar. PMID- 20306409 TI - Vocal cord dysfunction without end? AB - Vocal cord dysfunction (VCD) is an important differential diagnosis in acute dyspnoea. VCD is caused by adduction of the vocal folds during respiration typically leading to attacks of dyspnoea, stridor and coughing. Here we present an extraordinary case of an untypical paradoxical vocal fold adduction in a 15 year-old girl with stridor persisting over several weeks. PMID- 20306410 TI - Special Operations individual medical equipment part 2 - the in-use and survival medical kits. AB - Special Operations Forces (SOF) Operators need a variety of individual medical items that can generally be broken down into three types of medical kits: a major trauma kit, to treat major traumatic wounds; an in-use medical kit, to prevent or treat anticipated common medical conditions during operations; and a survival medical kit, to treat minor injuries and ailments when in a survival/evasion situation. PMID- 20306411 TI - Medical seminars: a new paradigm for SOF counterinsurgency medical programs. AB - Medical programs are valuable tools when they properly align with operational objectives. In counterinsurgency operations, the medical program should promote the capacity of the host nation government and lead to greater self-sufficiency. The Medical Civic Action Program (MEDCAP) often fails to fully integrate host nation providers and officials which may undermine local medical infrastructure and rarely provides sustainable improvement. The Medical Seminar (MEDSEM) was developed during Operation Enduring Freedom- Philippines to address the shortcomings of the traditional MEDCAP. The MEDSEM greatly enhanced the MEDCAP by adding education to the venue, thereby promoting self reliance and improving the sustainability of medical interventions. Furthermore, the MEDSEM forged relationships and promoted interoperability through collaboration between local medical providers, governmental leaders, host nation forces, and U.S. Special Operations Forces. PMID- 20306412 TI - Evidence-based diagnosis and management of mTBI in forward deployed settings: the genesis of the USASOC neurocognitive testing and post-injury evaluation and treatment program. PMID- 20306413 TI - Evaluation and treatment of persistent cognitive dysfunction following mild traumatic brain injury. AB - The Defense Centers of Excellence for Psychological Health and Traumatic Brain Injury (DCoE) and the Defense and Veterans Brain Injury Center (DVBIC) hosted a consensus conference to address persistent cognitive impairments following mild traumatic brain injury (mTBI) and the role of cognitive rehabilitation in this population. Fifty military and civilian subject matter experts developed clinical guidance for cognitive rehabilitation of Service members with cognitive symptoms persisting three or more months following injury. This article highlights the initial evaluation, comprehensive assessment and treatment recommendations contained within the guidance "Defense Centers of Excellence for Psychological Health and Traumatic Brain Injury and Defense and Veterans Brain Injury Center Consensus Conference on Cognitive Rehabilitation for Mild Traumatic Brain Injury." The full clinical guidance is available at: (http://www.dcoe.health.mil/Resources.aspx). PMID- 20306414 TI - Dislocation of the knee: imaging findings. AB - Dislocations of the knee are relatively uncommon injuries. However, the incidence of this injury appears to be increasing. Knee dislocations are most often high velocity blunt injuries, with motor vehicle accidents being a frequent etiology. Other causes include falls from height, athletic injuries, farming and industrial accidents, and even low velocity mechanisms such as a misstep into a hole. Likewise, minor trauma in the morbidly obese is increasingly recognized as a mechanism of knee dislocation. Multiple forms of dislocation exist, with the common factor being disruption of the tibiofemoral articulation. Dislocation can occur in a variety of directions depending on the mechanism of injury. The most common dislocation is anterior, which may be seen in hyperextension injuries such as martial arts kicking. The "dashboard injury" of motor vehicle accidents can result in a posterior dislocation of the knee. Lateral and rotary dislocations are less common. Knee dislocation is more commonly diagnosed in men, with a mean age of 23 to 31 years old. This is the very patient population encountered by Special Operations Forces (SOF) healthcare providers. Given the mechanisms of injury noted above, it is reasonable to conclude that knee dislocations may be seen in a young, active SOF patient population, particularly those engaged in parachuting, fast-roping/rappelling, driving at high speeds during military operations, and mixed martial arts. PMID- 20306415 TI - Monkey bite exposure treatment protocol. PMID- 20306416 TI - Canine tactical field care part three - thoracic and abdominal trauma. AB - Military and law enforcement agencies have seen a dramatic increase in the utilization of working canines both at home and in foreign deployments. Due to the fact that professional veterinary care is sometimes distant from internal disaster or foreign deployment sites, the military medic, police tactical medic, or other first-response medical care provider may be charged with providing emergency or even basic, non-emergency veterinary care to working canines. (Editor's Note: Military veterinary detachments are collocated next to the major human treatment facilities in a deployment environment. In a deployed environment veterinary care is located in areas where they are most needed or where most of the animals are located.) The medical principles involved in treating canines are essentially the same as those for treating humans, but the human healthcare provider needs basic information on canine anatomy and physiology and common emergency conditions in order to provide good basic veterinary care until a higher level of veterinary care can be obtained. This article represents the third in a series of articles designed to provide condensed, basic veterinary information on the medical care of working canines, to include military working dogs (MWDs), police canines, federal agency employed working canines, and search and rescue dogs, to those who are normally charged with tactical or first responder medical care of human patients. This article provides and overview of the diagnosis and treatment of common traumatic injuries to the thorax and abdomen. PMID- 20306417 TI - Portable ultrasound empowers Special Forces medics. PMID- 20306418 TI - "Damage control resuscitation for the Special Forces medic: simplifying and improving prolonged trauma care"(JSOM 2009, Vol 9, Eds 3-4) by Dr. Risk and Mike Hetzler, 18D. PMID- 20306419 TI - Editorial rebuttal. PMID- 20306420 TI - Medical sonography (ultrasonography). PMID- 20306422 TI - [Chronic obstructive pulmonary disease patients in the general practice]. AB - INTRODUCTION: Chronic obstructive pulmonary disease is one of the major public health problems because of its high prevalence, progressive nature and the costs involved in the treatment of and care for the patients with a diagnosis of COPD. MATERIAL AND METHODS: The study, for which 1026 patients were examined (86.3% of the patients registered), assessed how frequently COPD occurred, how advanced it was and how frequently it was underdiagnosed as well as its link to the smoking habit and the occurrence of concurrent diseases. RESULTS: COPD was diagnosed in 8.1% of the registered subjects above the age of 40 years, most of them either current or former smokers (90.3%); 61.3% of the patients were in the mild stage, 35.5%--the moderate stage, and 3.2%--severe COPD. The major factors contributing to the development of COPD are the number of pack-years and age. Women develop COPD with fewer pack-years then men. CONCLUSIONS: It was found that COPD is underdiagnosed in the general practice, since merely 1% of the patients had been correctly diagnosed before the study was conducted. One of the reasons for this is the fact that spirometric tests are not performed frequently enough. The statistically significant correlation between COPD and concomitant cardiovascular diseases was confirmed. PMID- 20306421 TI - [Acoustic rhinometry in the evaluation of intranasal aspirin challenge]. AB - Nasal lysine aspirin (Lys-ASA) challenge is an alternative to oral and bronchial challenges in the diagnosis of aspirin (ASA) hypersensitivity. The aim of the study was to evaluate the acoustic rhinometry as an objective method of assessment of Lys-ASA nasal challenge. MATERIAL AND METHODS: Twenty patients with aspirin induced asthma (ASA-S) and 10 controls (ASA-NS group: 5 patients with allergic rhinitis and 5 healthy subjects) were included. Nasal challenge was performed with placebo (saline) and 14.4 mg of Lys-ASA introduced as aerosol to both nostrils (total dose: 16 mg of acetylsalicylic acid). Measurements of nasal volume bilaterally were performed with the use of acoustic rhinometer before and 1, 2, 4 and 24 hours after the challenge. For further analysis the sum of both nasal cavities volume at the level of 2 to 5 cm from nostrils was used. RESULTS: Mean total bilateral volume in ASA-S group after placebo was: 7.74, 6.21, 7.11, 7.12, 7.24 cm(3) and 7.24, 5.77, 6.31, 6.27, 6.98 cm(3) after Lys-ASA (before and after 1, 2, 4 and 24 hours, respectively; p = 0,048 and p = 0,02, in 2nd and 4th hour, Lys-ASA v. placebo, Wilcoxon's test). With cut off point of nasal volume decrease by 10% in the 1st hour the sensitivity of the test was 70%, specificity 60%, positive predictive value 77.78% and negative predictive value 50%. CONCLUSIONS: In conclusion, acoustic rhinometry with measurement of nasal cavities volume changes at 2 to 5 cm from nostrils does not appear to be sufficiently sensitive and specific as a single method for evaluation of studied challenge method. PMID- 20306423 TI - [Prevalence of stroke in patients with obstructive sleep apnoea]. AB - INTRODUCTION: Results of earlier population and clinical studies confirmed relationship between stroke and obstructive sleep apnea. Our previous study on epidemiology of sleep-disordered breathing in Warsaw based on 676 subjects, mean age 56.6 +/- 8.2 years, confirmed OSA in 76 subjects (11.3%) mean apnea hypopnea index (AHI) - 25.3 +/- 16.1 revealed low incidence of stroke in OSA group (2 pts; 2.6%) and in subjects without OSA (20 pts; 3.4%). The aim of this study was to assess prevalence of stroke in newly diagnosed OSA subjects qualified to CPAP therapy. MATERIAL AND METHODS: We studied 342 consecutive pts (263 males and 79 females)--mean age--55.4 +/- 10.1 years with severe disease--AHI 39.7 +/- 22.5 and obesity--body mass index 35 +/- 6.6. History of stroke was confirmed in 16 pts before continuous positive airway pressure (CPAP) introduction (4.7%) - group 1. Group 2 (without history of stroke) comprised of 326 pts (95.3%). RESULTS: Multiple linear regression analysis revealed significant correlation between stroke and time spent in desaturation below 90% during polysomnography-- T90 (beta = -0.22, p = 0.009), diabetes (b = 0.16, p = 0.006), Epworth sleepiness score (beta = 0.14, p = 0.02) and coronary artery disease (b = 0.14, p = 0.03). CONCLUSIONS: Stroke in OSA pts before CPAP treatment was related to overnight and daytime oxygenation, diabetes, daytime sleepiness and coronary artery disease. Incidence of stroke in our group was low (4.7%) and similar to previous data from population study. PMID- 20306424 TI - [Integrated care for patients with advanced chronic obstructive pulmonary disease]. AB - Chronic obstructive pulmonary disease (COPD) is the third cause of mortality and disability (assessed by DALY) among patients above 60 year old. Severe and very severe COPD (FEV(1) = equal or less than 50% and 30% of expected value, respectively) is estimated at 20% of all COPD patients. Advanced COPD usually leads to physical and mental deterioration, the patients often manage with the problems caused by the disease and other comorbidities poorly. This leads to increased risk of COPD exacerbations and further deterioration of the patient's status, increased costs of medical care and eventually increased risk of death. Current organization of medical care for those patients does not provide adequate health and social support for them. However, it seems that introducing an integrated approach proposed by World Health Organization, could improve the situation of advanced COPD patients. In Poland, this kind of care has been provided in advanced cancer patients throughout stationary palliative care units and hospices during the last several years. This experience should be helpful in integrating actions of general practitioners and specialized nurses, as well as providing access for the specialists' consultations according to the individual needs of the patients. It should also allow for broad cooperation with auxiliary staff, such as social workers, medical assistants and volunteers, as well as psychologists and clergymen (especially in the terminal phase of the disease). PMID- 20306425 TI - [Clinical application of pulmonary function tests in preschool children]. AB - Pulmonary function tests are routinely used in the assessment of respiratory system in older children and adults. They have not made their way into wide clinical practice in preschool children and infants, mainly due to poor cooperation in this age group. This review discusses the use of various pulmonary function tests in preschool children in clinical setting. Issues relevant for clinical practice comprising but not limited to expressing results, within occasion repeatability and between occasion reproducibility of various tests as well as choosing reference data are described. This paper also examines the most frequent respiratory disorders in preschool children and potential impact of pulmonary function tests results on clinical management in these patients. PMID- 20306426 TI - [Lung mycobacteriosis--clinical presentation, diagnostics and treatment]. AB - Nontuberculous mycobacteria (NTM) are a group of bacteria that may cause human disease mycobacteriosis, but do not cause tuberculosis or leprosy. NTM are acquired through environmental exposure to water, aerosols, soil, dust and are transferred to humans through inhalation, ingestion, and skin lesions, due to injuries, surgical procedures, or intravenous catheters. People with suppressed immune response, with pre-existing lung damage in the course of various lung diseases are most likely to be affected. There is no evidence of person-to-person spread of these diseases. A variety of manifestations of NTM infection have been described, but the lungs remain the most commonly involved site. Molecular methods allow the quicker differentiation of NTM from TB isolates and help to identify new NTM species. The purpose of this article is to review the common clinical manifestations of NTM lung disease, the conditions associated with NTM lung disease, diagnostic criteria and treatment of the most frequent species of NTM. PMID- 20306427 TI - [Obstructive sleep apnea in patient with Prader-Willi syndrome]. AB - Prader-Willi syndrome (PWS) is a genetic disorder caused by loss of function of genes situated within the 15q11-q13 region of chromosome 15. The disorder is characterized by central obesity, short stature, dysfunction of several hypothalamic centers. These symptoms lead to progressive metabolic, respiratory, circulatory and orthopedic complications. Because of the etiology of the disorder there is no known causal treatment. Patients should comply with dietary restrictions and behavioral modifications as it may reduce the risk of obesity related diseases. In this paper we present case of a 34-years old obese patient with PWS who was diagnosed with obstructive sleep apnea, and whom CPAP treatment was offered. PMID- 20306428 TI - [Acquired methemoglobinemia--case report]. AB - Methemoglobinemia; an increased concentration of methemoglobin in the blood, is an altered state of hemoglobin whereby the ferrous form of iron is oxidized to the ferric state, rendering the heme moiety incapable of carrying oxygen. The authors present a case of 49-year-old man who was admitted to the department of chest medicine with dyspnea, weakness and cyanosis in whom differential diagnosis excluded acute and chronic pulmonary and cardiovascular disease. Clinical cyanosis and low measured oxygen saturation in the presence of normal arterial oxygen tension was highly suggestive of methemoglobinemia ("saturation gap"). Methemoglobin level, measured at the acute phase of disease was elevated at 16%. Episode resolved spontaneously. Causes of methemoglobinemia was not established. PMID- 20306429 TI - [Fourth Polish-French Pulmonary Conference, Wroclaw, October 16th-18th 2009]. PMID- 20306430 TI - [Cultural conditionalities of cigarette smoking. Commentary to the article of Sieminska A. et al. "Medical students' attitudes towards tobacco smoking at first and sixth year of their studies 2002-2008"]. PMID- 20306432 TI - Development of a novel large animal model of ischemic heart failure using autologous platelet aggregates. AB - BACKGROUND: Current animal models of heart failure lack the biomass of thrombus that occurs in patients undergoing myocardial infarction. We propose a novel animal model of ischemic cardiomyopathy developed by sequential direct injections of autologous platelet aggregates into the coronary circulation resulting in development of ischemic cardiac insufficiency. METHODS: Autologous platelets from adult sheep were isolated and aggregated. Aggregated platelets were then injected into the coronary circulation of anesthetized animals under fluoroscopic guidance. Troponin I levels were monitored for first three days after embolization to validate cardiac tissue injury. Progression of heart failure was corroborated by monitoring changes in echo-based assessment of ejection fraction and left ventricular end-systolic and end-diastolic dimensions. Thrombus-based obstruction of coronary artery was confirmed with histopathology review by mepacrine labeling of pre-aggregated platelets. RESULTS: All experimental animals developed heart failure-like cardiac insufficiency confirmed by elevated levels of troponin I and associated with significant drop in the ejection fraction. CONCLUSIONS: Sequential injections of aggregated platelets into coronary circulation lead to progressive development of ischemic cardiac insufficiency. This phenomenon seems to mimic development of ischemic heart failure seen in human patients and opens multiple research opportunities to fill the existing gap between basic research and clinical practice. PMID- 20306433 TI - Major factors of homologous blood transfusion in valvular heart operation with intraoperative autologous blood predonation in cases with difficulty in preoperative predonation. AB - Intraoperative autologous blood predonation is reported to be useful for the prevention of homologous blood transfusion in cardiac operations, especially in on-pump coronary artery bypass grafting (CABG). However, CABG is now performed more often off-pump than on-pump. We analyzed the major factors of homologous blood transfusion in 25 consecutive cases of valvular heart operation with intraoperative autologous blood predonation except those with preoperative autologous blood donation. Homologous blood was not transfused in 18 cases, but was in 7 cases only after cardiopulmonary bypass (CPB). The homologous transfusion was not correlated with body weight, CPB dilution or duration, or preoperative hematocrit level, but was found to correlate with age (r2=0.289, p=0.0413), bleeding output (r2=0.197, p=0.0485), and predonation blood volume (r2=0.436, p=0.0152). In conclusion, suitable intraoperative predonation may reduce the necessity for homologous blood transfusion in valvular heart operations. PMID- 20306434 TI - Comparative study of different techniques for the sterilization of poly-L-lactide electrospun microfibers: effectiveness vs. material degradation. AB - Electrospinning of biopolymeric scaffolds is a new and effective approach for creating replacement tissues to repair defects and/or damaged tissues with direct clinical application. However, many hurdles and technical concerns regarding biological issues, such as cell retention and the ability to grow, still need to be overcome to gain full access to the clinical arena. Interaction with the host human tissues, immunogenicity, pathogen transmission as well as production costs, technical expertise, and good manufacturing and laboratory practice requirements call for careful consideration when aiming at the production of a material that is available off-the-shelf, to be used immediately in operative settings. The issue of sterilization is one of the most important steps for the clinical application of these scaffolds. Nevertheless, relatively few studies have been performed to systematically investigate how sterilization treatments may affect the properties of electrospun polymers for tissue engineering. This paper presents the results of a comparative study of different sterilization techniques applied to an electrospun poly-L-lactide scaffold: soaking in absolute ethanol, dry oven and autoclave treatments, UV irradiation, and hydrogen peroxide gas plasma treatment. Morphological and chemical characterization was coupled with microbiological sterility assay to validate the examined sterilization techniques in terms of effectiveness and modifications to the scaffold. The results of this study reveal that UV irradiation and hydrogen peroxide gas plasma are the most effective sterilization techniques, as they ensure sterility of the electrospun scaffolds without affecting their chemical and morphological features. PMID- 20306435 TI - Synthesis and characterization of a laminated hydroxyapatite/gelatin nanocomposite scaffold with controlled pore structure for bone tissue engineering. AB - In this study, a nanostructured scaffold was designed for bone repair using hydroxyapatite (HA) and gelatin (GEL) as its main components. Nanopowders of HA were synthesized, and together with GEL, used to engineer a 3-dimensional nanocomposite combining 3 techniques of layer solvent casting, freeze-drying, and lamination. The results show that the scaffold possesses a 3-dimensional interconnected homogenous porous structure with a porosity of 82% and pore sizes ranging from 300 to 500 mum. It has also been shown that mechanical indices are in the range of spongy bones. Cultured osteoblast-like cells (SaOS-2) have shown an excellent level of cell attachment, migration, and penetration into the porosities of the nanocomposite scaffold. Here, we have shown that by a combination of widely available methods with simple experimental operations, nano HA powders can be synthesized and used to make 3-dimensional HA/GEL nanocomposites in any desired shape, with mechanical properties comparable to spongy bone. PMID- 20306436 TI - HPLC study of uremic fluids related to optical dialysis adequacy monitoring. AB - PURPOSE: The aim of this study was to investigate uremia-related high-performance liquid chromatography (HPLC) ultraviolet (UV) absorbance profiles of serum and spent dialysate and to study the removal of uremic retention solutes in connection with optical dialysis adequacy monitoring. METHODS: 10 uremic patients were investigated using online spectrophotometry at a wavelength of 280 nm over the course of 30 hemodialysis treatments. The dialysate and blood samples were taken and analyzed simultaneously using standard biochemical methods and reversed phase HPLC. Filters with cutoff at 3 kDa and 70 kDa were used for the pre treatment of the serum. The chromatographic peaks were detected by a UV detector at wavelengths of 254 and 280 nm. RESULTS: This study indicated that the main solute responsible for UV absorbance in the spent dialysate is a low-molecular weight, water-soluble, non-protein-bound compound uric acid (UA). Three additional uremic retention solutes - creatinine (CR), indoxyl sulphate (IS) and hippuric acid (HA) - were identified from the HPLC profiles. The number of detected HPLC peaks was not significantly different for a serum filtered through the 3 kDa or 70 kDa cutoff filters, and was lower for the spent dialysate, indicating that the molecular weight (MW) of the main UV chromophores in the uremic fluids did not exceed 3 kDa. The reduction ratio (RR) estimated by the total area of HPLC peaks at 254 nm and 280 nm in the serum and by the online UV absorbance at 280 nm was best related to the removal of small water-soluble non protein bound solutes like urea (UR), CR and UA. CONCLUSIONS: The present study contributes new information on the removal of uremic retention solutes during hemodialysis and on the origin of the optical dialysis adequacy monitoring signal. PMID- 20306437 TI - Treatment with bioartificial liver improves lung injury in a swine model of partial hepatectomy and ischemia/reperfusion. AB - PURPOSE: Hepatic ischemia/reperfusion injury can lead to remote lung injury by inducing oxidative stress and inflammation. this study aims to investigate whether support of liver function with a bioartificial liver can attenuate remote lung injury after extended hepatectomy. METHODS: Fourteen domestic pigs were subjected to liver ischemia for 150 minutes and 70-75% hepatectomy. Six hours after initiation of hepatic reperfusion the animals were randomly allocated to a 6-hour treatment with a bioartificial liver (group b, n=7) or observation (group C, n=7). Hemodynamic and metabolic parameters were monitored for 24 hours following reperfusion. Lung biopsies were used for histological, nitrotyrosine and mrNA analysis. RESULTS: Oxygenation gradually deteriorated in group C, but was not significantly impaired in group b. Histological evaluation revealed improvements in alveolar collapse, necrotized pneumonocytes and lymphocyte infiltration in group b. Nitrotyrosine content of the lung was lower in group b compared to group C (55+/-12 vs. 132+/-22 nM/mg protein, p<0.01). Lung mrNA expression of interleukin-6, Stat-3 and E-selectin also decreased in group b. Expression of transforming growth factor-alpha mrNA did not differ between groups. CONCLUSIONS: Application of a bioartificial liver was associated with improvement in several parameters of post-hepatectomy lung injury. the mechanisms appear to involve reduced nitrosative stress and attenuation of the native inflammatory process in the lung. PMID- 20306438 TI - Crush syndrome after the Wenchuan earthquake: new experience with regional citrate anticoagulation continuous veno-venous hemofiltration. AB - PURPOSE: Acute renal failure (ARF) related to crush syndrome is usually treated with hemodialysis. Continuous veno-venous hemofiltration (CVVH) has seldom been adopted in this situation due to the main drawback of continuous anticoagulation. The purpose of this study was to evaluate the effectiveness and safety of regional citrate anticoagulation (RCA)-CVVH in two crush syndrome patients following the Wenchaun earthquake. METHODS: Two victims from the Wenchuan earthquake in Southwest China were admitted to our hospital on May 23, 2008, 11 days after their injury. The total entrapment time under the rubble was 5.5 and 22.5 hrs respectively. They remained oliguric on admission, in spite of vigorous treatment in the local hospital including aggressive fluid infusion, fasciotomy and intermittent hemodialysis. On admission, their serum myoglobin levels were 765 and 829 ng/mL, respectively. Further debridement and drainage were performed. RCA-CVVH was conducted; the citrate containing substitution fluid was infused in a pre-dilution manner at a rate of 4 l/h; calcium was infused through a separate access to the venous inlet of the double lumen catheter. The infusion rate was adjusted according to the serum ionized calcium and whole blood activated clotting time (WBACT). A low dose of low molecular weight heparin (LMWH) was infused at the rate of 150 approximately 300 U/h simultaneously for anticoagulation after anemia had been corrected and their wounds were stable. RCA CVVH was substituted by conventional CVVH and LMWH anticoagulation when case 2 complicated with hypoxia. RESULTS: RCA-CVVH was well tolerated, hemodynamic status was stable, and no complications related with RCA-CVVH were noted. The body temperature and WBC decreased to normal range, while anemia and hypoalbuminia were corrected. The levels of serum myoglobin and creatine phosphokinase were also decreased to normal range. Their urine volume increased after 20 and 22 days of oliguria and the tubular function of the patients recovered well. Although the second case encountered acute cholecystitis and acute lung injury in the hospital, both the patients recuperated and neither of them underwent amputation. CONCLUSIONS: The present two crush patients have been successfully treated, but due to the limits of the small sample, it is difficult to generalize whether RCA-CVVH is safe enough for crush syndrome with a high risk of bleeding diathesis. Additional investigation with a larger number of patients is required. Fluid equilibrium, nutritional support, prevention of bleeding and infection are fundamental in this situation. PMID- 20306439 TI - Multifocal electroretinogram and central visual field testing in central areolar choroidal dystrophy. AB - PURPOSE: To study multifocal electroretinogram (mfERG) and its relation to retinal sensitivity assessed by Humphrey visual field (HVF) analysis in central areolar choroidal dystrophy (CACD). METHODS: Seven eyes of 4 patients with CACD and 15 normal control subjects were examined. mfERG and central 30/2 HVF were tested for each participant. Ring analysis in mfERG was evaluated. HVF results were evaluated in 5 concentric rings in order to compare the results to concentric ring analysis in mfERG. The differences between control subjects and patients were evaluated by Mann-Whitney U test and the correlations were assessed by Spearman test. RESULTS: Mean Snellen acuity was 0.49+/-0.10 in patients. HVF revealed central scotoma in 6 of 7 eyes (85.7%), whereas a paracentral scotoma extending to fixation point was detected in 1 eye. The retinal sensitivities in 5 concentric rings in HVF were significantly lower (p<0.001 for ring 1 to ring 4, and p=0.017 in ring 5) in CACD patients. Similarly, CACD patients had lower P1/N1 amplitudes (p<0.05) and delayed P1/N1 implicit times (p<0.05). CONCLUSIONS: In CACD, in the areas of scotoma detected by HVF, mfERG values were depressed. However, both mfERG and HVF abnormalities were found outside the areas of ophthalmoscopically normal retinal areas. PMID- 20306440 TI - Intravitreal ranibizumab in the treatment of choroidal neovascularization associated with idiopathic central serous chorioretinopathy. AB - PURPOSE: We evaluate the functional and anatomic outcome after intravitreal ranibizumab treatment in patients with choroidal neovascularization (CNV) related to chronic central serous chorioretinopathy (CSC). METHODS: This is a small case series of 5 eyes with CNV associated with chronic CSC treated with intravitreal injection of 0.5 mg ranibizumab in the Jules Gonin University Eye Hospital from July 2007 to July 2009. Baseline and monthly follow-up visits included best corrected visual acuity (BCVA), fundus examination, and optical coherence tomography (OCT). Fluorescein and indocyanine green angiography (ICG) were performed at baseline and repeated at least every 6 months. RESULTS: We studied 5 eyes of 4 patients with a mean age of 66 years. Mean follow-up was 21 months (SD 1.9). The mean number of intravitreal injections administered for each patient was 10 (SD 4.6). The mean initial BCVA was 0.23 (decimal equivalent) (logMAR 0.64, SD 0.13). At the last follow-up, mean BCVA was 0.44 decimal equivalent (logMAR 0.36, SD 0.31). Mean central macular thickness (CMT) measured with OCT was 330 microm (SD 43) at baseline and decreased at the final follow-up to 243 microm (SD 44 ). Persistent intraretinal or subretinal fluid on OCT and/or multifocal areas of increased choroidal permeability on ICG angiographies were present in all patients at the last follow-up visit. CONCLUSIONS: Intravitreal ranibizumab appeared to be an effective treatment of CNV related to chronic CSC. However, residual intraretinal or subretinal fluid and increased choroidal permeability persisted. Prospective controlled studies are warranted to evaluate the long-term safety and efficacy of intravitreal ranibizumab. PMID- 20306441 TI - Ex-PRESS miniature glaucoma device in vitrectomized eyes. AB - PURPOSE: To evaluate the clinical efficacy and safety of the Ex-PRESS miniature glaucoma device placed under scleral flap for the treatment of ocular hypertension in eyes that underwent vitreoretinal surgery. METHODS: Vitrectomized patients who required glaucoma surgery for persistent ocular hypertension were included. The Ex-PRESS miniature glaucoma device was implanted under scleral flap. Postsurgical clinical outcomes and intraocular pressure (IOP) was monitored for 6 months after surgery. RESULTS: At 6 months, all the patients had an IOP lower than 18 mmHg, 3 of them without topical therapy. CONCLUSIONS: The use of the Ex-PRESS implant under scleral flap in eyes that underwent vitreoretinal surgery was effective for lowering IOP. PMID- 20306442 TI - Rarebit perimetry in the evaluation of visual field defects in idiopathic intracranial hypertension. AB - PURPOSE: Rarebit perimetry (RBP) is a new perimetric technique that has been reported as a sensitive test for the evaluation of the neural structure of the visual system. The aim of this study was to compare RBP with standard automated perimetry in detecting the visual field defects of patients with idiopathic intracranial hypertension (IIH). METHODS: Twenty-five patients with IIH and 16 healthy controls were considered. Visual fields were analyzed with Marco automated static perimeter with threshold and central 30-2 programs (MP 30-2) and rarebit perimetry. A visual field was classified into 3 zones for both tests as central, paracentral, and peripheral zones. Mean sensitivity (MS) recorded by the MP 30-2 was compared with the mean hit rate (MHR) recorded by RBP for each zone. RESULTS: MS recorded by MP 30-2 and MHR recorded by RBP for each zone were significantly lower in the IIH group than in healthy control eyes (p < 0.001). Good correlation was present between the visual fields recorded by both tests. Although the sensitivity and specificity values for each zone were lower in the RBP group than the MP 30-2 group, RBP was found to be efficient to differentiate between the visual fields of normal and IIH-affected eyes. The average RBP test duration was significantly shorter than the MP 30-2 test duration (p < 0.001). CONCLUSIONS. RBP is a rapid, comfortable, and widely accessible perimetric test giving reliable results in detecting visual field defects in IIH. PMID- 20306443 TI - Intravitreal carboplatin concentration and area under concentration versus time curve after intravitreal and periocular delivery. AB - PURPOSE: To determine platinum (Pt) concentrations and area under the concentration versus time curve (AUC) of the vitreous humor after periocular or transcorneal intravitreal administration of carboplatin in rabbits. METHODS: Eighteen albino rabbits were included in an in vivo experiment. Each animal received a single dose of either 30 mg of carboplatin by periocular injection (POI30 group: n = 6) or 15 mg by periocular injection (PI15 group: n = 6), or 0.05 mg by transcorneal intravitreal injection (TII group: n = 6), respectively, into the right eye. Vitreous humor from the right eyes and plasma samples were collected post dose at 1, 2, 6, 24, 48, 168, and 336 hours or 448 hours, respectively. Flameless atomic absorption spectroscopy was employed to analyze total platinum concentrations in blood and vitreous humor. AUC was calculated using the trapezoidal rule. RESULTS: Pt concentration was mostly < 1 mg/L (0-3.15 mg/L) in the vitreous humor samples and > or = 2 mg/L (2.33-7.3 mg/L) in the blood samples 1 hour after administration in POI groups. Markedly higher Pt concentrations were found 1 hour after intravitreal (TII) administration (10.285 66.759 mg/L) and decreased below 1 mg/L no less than 168 hours after administration. The mean AUC for Pt in vitreous humor was significantly lower (p = 0.0001) after both POI30 and P0I15 administration compared to TII route (8.955 +/- 2.464 mg/L/min). CONCLUSIONS: These findings proved that intravitreal carboplatin delivery enables the achievement of relatively stable concentrations and AUC of platinum in the rabbit vitreous humor. This moreover suggests that transcorneal intravitreal delivery of carboplatin aiming to treat retinoblastoma vitreous seeding is a promising mode of chemotherapy. PMID- 20306444 TI - Comparison of the transpalpebral tonometer TGDc-01 with Goldmann applanation tonometry. AB - PURPOSE: This study aimed to compare intraocular pressure (IOP) measurements obtained by the transpalpebral tonometer TGDc-01 and by the Goldmann applanation tonometer (GAT). METHODS: IOP was measured by the conventional GAT and the TGDc 01 tonometer. Central corneal thickness (CCT) was measured for all eyes. RESULTS: Sixty-seven consecutive patients (123 eyes) participated. The mean difference between the 2 techniques (TGDc-01-GAT) was -0.93 mmHg, SD=2.74 (p=0.0002, paired t-test), and 70% of the measurements were within +/-2 mmHg. The correlation coefficient was 0.67 (p<0.0001). A subgroup analysis according to CCT was conducted. For CCT <520 microm, the mean IOP difference was 0.67 mmHg (p=0.13); r=0.75 (p<0.001). For CCT 520 microm-580 microm, the mean IOP difference was 1.08 mmHg (p=0.001); r=0.69 (p<0.0001). For CCT>580 microm, the mean IOP difference was -2.29 mmHg (p=0.0003); r=0.57 (p=0.003). CONCLUSIONS: TGDc-01 may estimate IOP with a fair agreement to the Goldmann tonometer, although caution should be used for patients who require precise IOP measurements. TGDc-01 measured higher IOPs than Goldman tonometry for thinner corneas, a trend that was reversed for thicker corneas. This tonometer is a portable device, easy to use, does not require anesthetic drops, and may be suitable for IOP screening. PMID- 20306445 TI - Familial clustering of diabetic retinopathy in Chongqing, China, type 2 diabetic patients. AB - PURPOSE: To investigate whether there is familial aggregation of diabetic retinopathy (DR) among type 2 diabetes mellitus (T2DM) patients in Chongqing, the municipality in southwest China. METHODS: From December 2004 to December 2006, 167 T2DM families with at least 2 diabetic siblings were investigated. In all 414 subjects, the sibling with the longest duration of diabetes was defined as the proband. The occurrence of retinopathy was compared between the siblings of probands with and without retinopathy. DR risk factors of the siblings of probands were studied by multiple logistic regression analysis. RESULTS: DR was diagnosed in 7.1% of the siblings of the probands without DR and in 29.7% of the siblings of the probands with DR. The difference reached statistical significance in probands with DR and probands without DR (p<0.0001). Nonesterified fatty acid (NEFA) was a risk factor for DR (odds ratio = 2.108, 95% confidence interval 1.077-4.127). It appeared that regardless of probands with DR, siblings with history of smoking had less risk for developing DR than those with no history of smoking. CONCLUSIONS: Familial clustering of DR existed in the patients with T2DM in Chongqing, China. In DR siblings, NEFA is a risk factor of DR, while smoking may reduce DR occurrence. PMID- 20306446 TI - Choroidal lymphoma masquerading as anterior ischemic optic neuropathy. AB - PURPOSE: To report a patient with presumed nonarteritic anterior ischemic optic neuropathy (NAION) found on our evaluation to have bilateral uveal lymphoma. METHODS: The clinical history and physical examination, Humphrey visual field testing, ultrasonography, magnetic resonance imaging (MRI), and fine needle aspiration biopsy specimen of a 60-year-old man with presumed NAION were evaluated. RESULTS: The patient initially presented with painless blurred vision OD and foreign body sensation OS. Upon examination, he was found to have optic nerve edema OD suspicious for NAION and oral steroids were employed with no improvement. Later, an abnormality in the left eye raised suspicion for choroidal metastasis. By ultrasound, the tumor in the left choroid was acoustically hollow. MRI of the orbits revealed a choroidal infiltrative process OU. Fine needle aspiration biopsy of OS confirmed atypical lymphocytes, predominantly small to intermediate sized, without necrosis. The patient was treated with external beam radiation therapy to both eyes. CONCLUSIONS: Choroidal lymphoma may present with clinical features of anterior ischemic optic neuropathy or choroidal metastasis. PMID- 20306447 TI - Serum neutrophil gelatinase-associated lipocalin in patients with colorectal liver metastases: preliminary results of an exploratory prospective study. AB - PURPOSE: To quantify preoperative serum neutrophil gelatinase-associated lipocalin (NGAL) levels in patients undergoing curative resection of colorectal liver metastases and to assess the relationship between NGAL levels and prognostic features in these patients. METHODS: From April 2005 to August 2007, 32 patients operated on for first curative resection of colorectal liver metastases underwent determination of preoperative serum NGAL. Patients were divided into four homogeneous clinical groups and into two risk groups based on their clinical risk scores. NGAL levels were corrected by simultaneous creatinine levels to avoid bias due to renal failure. RESULTS: Higher values of corrected NGAL levels (CNL) were found in patients of the high-risk group (94.53+/-56.18 vs 57.87+/-24.49, p=0.014). Patients with more than three tumor nodules had higher values of CNL compared to patients with three or fewer nodules (101.78+/-56.35 vs 58.57+/-27.24, p=0.008). Patients with disease involving both hepatic lobes had higher CNL levels than those with involvement of a single lobe (106.5+/-59.13 vs 59.01+/-26.69, p=0.005). Patients with higher clinical risk scores had significantly higher CNL. CONCLUSIONS: CNL are associated with the considered prognostic clinical factors and scores, suggesting a possible role for CNL as a prognosis-related indicator and a neoplastic tissue volume marker in patients with colorectal liver metastases. PMID- 20306449 TI - No mutation detected in five hot spot codons of the TP53 gene by restriction site mutation analysis in patients with carcinoma of the tongue. AB - The present study evaluated 5 of the 8 main TP53 mutation hot spots in cancer by restriction site mutation analysis and compared the results with p53 protein expression in patients with cancer of the tongue. Tumor samples from 49 patients with tongue cancer were screened for TP53 mutations in exons 5 through 8 by PCR restriction site mutation analysis and for p53 protein expression by immunohistochemistry using the DO-7 antibody. Nuclear accumulation of p53 protein was seen in 22% (11/49) of the tumors, whereas none of the patients exhibited TP53 mutations in exons 5 through 8. The observed data suggest that TP53 mutations alone are not responsible for abnormal accumulation of p53 protein in tobaccochewing-mediated tongue carcinogenesis. PMID- 20306448 TI - An alternative cyclin-D1 splice site is not linked to inflammatory bowel disease associated neoplasia. AB - BACKGROUND: Inflammatory bowel diseases (IBD) encompass inflammatory disorders affecting the gastrointestinal tract, primarily ulcerative colitis (UC) and Crohn's disease (CD). The risk of developing colorectal cancer (CRC) is increased in patients with IBD. The CCND1 protein is the regulatory subunit of an enzyme that inactivates the retinoblastoma protein, a tumor suppressor protein, and promotes progression through the G1-S phase of the cell cycle. The CCND1 870G-A gene polymorphism influences susceptibility to colorectal cancer. The mutant allele of CCND1 in IBD-associated neoplasia leads to a greater frequency of alternate splicing during transcription, resulting in a more stable CCND1 protein. This creates a higher concentration of CCND1, facilitating easier passage through the G1/S checkpoint, abnormal cell cycle progression, and possibly carcinogenesis. METHODS: We conducted a case-control study involving 396 individuals with IBD. IBD subgroups included CD, UC, and indeterminate colitis (IC). We studied patients with sporadic colorectal cancer (n=75) and patients without gastrointestinal disease as a control group (n=93). We extracted DNA from blood and performed polymerase chain reaction followed by high-performance liquid chromatography to screen for mutations. We confirmed the polymorphism at nucleotide A870G in exon 4. For statistical analysis, we used exact analyses of two-way contingency tables. Power calculations were done and correction for multiple testing was performed by computing the false discovery rate (FDR). RESULTS AND DISCUSSION: Our study had a power of 75% at a 0.05 significance level. A870G SNP allele frequency in the IBD group was 44.8%, compared to 51.6% in the control population. Only the IC group showed a significant association with CCND1 splice site after correction for multiple testing (FDR=0.042). There were no differences between the other IBD groups and controls. CONCLUSION: We found an association between CCND1 A870G SNP and IC group only (p=0.014, FDR=0.042). However, our data do not show an association between CCND1 A870G SNP and CD-associated or UC-associated neoplasia. PMID- 20306450 TI - Diagnostic and prognostic significance of inflammatory markers in lung cancer associated pleural effusions. AB - Besides massive expression in inflammatory pleural effusions, inflammatory markers are also present in cancerinduced pleural effusions. Recent advances in cancer biology point to a role of inflammatory signaling in cancer and encourage reconsidering the diagnostic and prognostic value of inflammatory markers. Here an attempt was made to relate protein levels of inflammatory markers to underlying malignant processes in the pleural space. Pleural effusions from lung cancer patients (n=116) were subjected to a multifactorial analysis covering 13 inflammatory markers. The composition of tumor-associated effusions was compared with that of parainflammatory pleural effusions (n=30), transudates (n=18), and serum values, and evaluated in relation to cancer origin, histology, cytology, pleural involvement, treatment history, and survival time. Inflammatory markers were significantly expressed in pleural effusions of paraneoplastic origin when compared to transudates and most serum levels. Values in pleura-invading and metastatic tumor-associated effusions were typically higher than those of other tumors. Many markers correlated negatively with survival, most prominently IL-8 (r=-0.36, p=0.001) and VEGF (r=-0.35, p=0.001). It appears that most inflammatory markers are highly expressed in tumor-associated pleural effusions, reflecting to some extent tumor origin and localization. Despite the lower efficacy of inflammatory markers in the differentiation between exudative pleural effusions, some inflammatory markers may represent potential prognostic markers of malignant processes in the pleural space. PMID- 20306452 TI - Issues in multiple imputation of missing data for large general practice clinical databases. AB - PURPOSE: Missing data are a substantial problem in clinical databases. This paper aims to examine patterns of missing data in a primary care database, compare this to nationally representative datasets and explore the use of multiple imputation (MI) for these data. METHODS: The patterns and extent of missing health indicators in a UK primary care database (THIN) were quantified using 488 384 patients aged 16 or over in their first year after registration with a GP from 354 General Practices. MI models were developed and the resulting data compared to that from nationally representative datasets (14 142 participants aged 16 or over from the Health Survey for England 2006 (HSE) and 4 252 men from the British Regional Heart Study (BRHS)). RESULTS: Between 22% (smoking) and 38% (height) of health indicator data were missing in newly registered patients, 2004-2006. Distributions of height, weight and blood pressure were comparable to HSE and BRHS, but alcohol and smoking were not. After MI the percentage of smokers and non-drinkers was higher in THIN than the comparison datasets, while the percentage of ex-smokers and heavy drinkers was lower. Height, weight and blood pressure remained similar to the comparison datasets. CONCLUSIONS: Given available data, the results are consistent with smoking and alcohol data missing not at random whereas height, weight and blood pressure missing at random. Further research is required on suitable imputation methods for smoking and alcohol in such databases. PMID- 20306451 TI - Assessment of biomarkers for clinical diagnosis of papillary thyroid carcinoma with distant metastasis. AB - Early diagnosis and treatment of thyroid cancers are critical for better prognosis and better survival rates. The purpose of this study was to identify potential diagnostic markers for papillary thyroid carcinomas with distant metastasis. Fifty-eight papillary thyroid tumor specimens (27 papillary thyroid carcinomas with distant metastasis and 31 without metastasis) were examined, and protein expression of pituitary tumor-transforming gene (PTTG), E-cadherin, p27kip1, vascular endothelial growth factor (VEGF)-C, metalloproteinase (MMP) 2, MMP9, chemokine receptor CXCR4, and basic fibroblast growth factor (bFGF) in these tumors was assessed by immunohistochemistry. The clinicopathological variables with diagnostic significance were determined by multivariate analysis, and their diagnostic values were evaluated by ROC curve analysis. PTTG, VEGF-C, MMP2, MMP9, CXCR4, and bFGF were overexpressed in metastatic papillary thyroid carcinomas, whereas p27kip1 expression was elevated only in carcinomas lacking metastasis. Multiple-factor binary ordinal logistic regression analysis revealed that PTTG, VEGF-C, MMP2, and bFGF were independently related to biological metastatic behavior in thyroid tumors, suggesting their potential use as biomarkers. ROC curve analysis showed that among these four proteins, VEGF-C and bFGF were the best diagnostic biomarkers. A VEGF-C and bFGF cluster was the most useful factor for the differential diagnosis between metastatic and non metastatic papillary thyroid cancers. Thus, the combined use of VEGF-C and bFGF as biomarkers may improve the diagnostic accuracy of papillary thyroid carcinoma and may be useful in multimodal screening programs for the clinical diagnosis of papillary thyroid carcinoma and early detection of papillary thyroid carcinoma with distant metastasis. PMID- 20306453 TI - Laboratory monitoring and adverse patient outcomes with antihypertensive therapy in primary care. AB - PURPOSE: The monitoring of serum electrolyte and creatinine concentrations in patients treated with antihypertensive therapy is recommended. We wished to examine the relationship between laboratory monitoring and adverse patient outcomes. METHODS: We carried out a retrospective cohort study using the General Practice Research Database (GPRD). Patients aged 18 years or older with newly diagnosed hypertension and prescribed a single antihypertensive agent were included. Monitoring was defined as any laboratory test for serum electrolyte and creatinine (or urea) concentrations within 6 months of starting treatment. RESULTS: We identified 74 096 patients who were newly diagnosed with hypertension and prescribed a single antihypertensive agent. Twenty six thousand nine hundred forty six (36.4%) patients had any biochemical laboratory measurement within 6 months. Three hundred ten patients (0.4%) died, 1451 (2%) were admitted to hospital at least once and 29 749 (40.2%) discontinued their first course of antihypertensive treatment within 6 months. Patients were more likely to be admitted to hospital if their biochemistry had been monitored after beginning treatment (adjusted hazard ratio (HR) 1.37; 95%CI 1.21-1.55). They were also marginally more likely to discontinue treatment (adjusted HR 1.04; 95%CI 1.02 1.07). They were not significantly more likely to die (adjusted HR 1.21; 95%CI 0.87-1.67). CONCLUSIONS: Biochemical testing at baseline and monitoring after starting treatment is often omitted in newly diagnosed hypertensive patients. Those patients who are monitored are more likely to be admitted to hospital and to discontinue initial antihypertensive therapy, but not to die. Many biochemical adverse drug reactions are found only by laboratory monitoring. PMID- 20306454 TI - Neuroleptic malignant syndrome and its controversies. AB - PURPOSE: Neuroleptic malignant syndrome (NMS) is a rare and life threatening condition usually defined as a complication of treatment with antipsychotics characterized by severe rigidity, tremor, fever, altered mental status, autonomic dysfunction, and elevated serum creatine phosphokinase and white blood cell count. The literature on this topic is rather extensive, but many aspects related to the syndrome are thought to be controversial. The aim of this paper, written with the clinician in mind, is to summarize some of the most prominent controversies that may have importance in usual clinical practice. METHODS: The literature was searched for reviews, reports on the series of cases, individual case reports of NMS, and other clinically and theoretically important information. RESULTS: There are controversies associated with virtually all important aspects of NMS. At the moment, it is not clear if this drug reaction is idiosyncratic or not, what diagnostic criteria are the most appropriate for usual clinical practice, and it seems that the estimated incidence is not in accordance with the number of treated patients. There are rather different approaches to the pathophysiological mechanisms, differential diagnosis, and treatment. CONCLUSIONS: Some of the controversies related to NMS have an influence on our understanding of the condition and may have importance in clinical practice. There is a need for further research that should elucidate these controversies. PMID- 20306455 TI - Estimating the prevalence of inflammatory bowel disease in Portugal using a pharmaco-epidemiological approach. AB - PURPOSE: To estimate inflammatory bowel disease (IBD) prevalence in Portugal from 2003 to 2007, and to obtain disease, sex and age specific estimates. METHODS: A pharmaco-epidemiological approach based on intestinal anti-inflammatory (IAI) drugs consumption was used. Proportion of patients taking IAI drugs and mean prescribed daily dose (PDD) were estimated from a sample of 513 IBD patients. Assumptions were made about unknown parameters and sensitivity analysis performed: drug compliance (80% in base case; range 70-85%) and proportion of sulphasalazine used in IBD (52%; range 40-80%). Sex and age specific estimates were based on a proposed methodological extension and results from a nationwide (n = 5893) cross-sectional study. RESULTS: IBD prevalence increased from 86 patients per 100 000 in 2003 to 146 in 2007. Regions more affected were Lisboa and Porto (173 and 163 per 100 000 in 2007, respectively). Prevalence increased from 42 and 43 per 100 000 in 2003 to 71 and 73 in 2007, respectively for ulcerative colitis (UC) and Crohn's disease (CD). In 2007, prevalence was higher in the 40-64 age stratum for UC (99 per 100 000) and in the 17-39 stratum for CD (121). Prevalence was consistently higher in females. CONCLUSIONS: Portugal is half way between countries with the highest and lowest IBD prevalence, but is steeply making the road to the highest-level group. Despite limitations of the proposed methods, assumptions were reasonable and estimates seem to be valid. Feasibility and comparability of this methodology makes it an interesting tool for future studies on IBD epidemiology. PMID- 20306456 TI - Mapping of a standard documentation template to the ICF core sets for arthritis and low back pain. AB - BACKGROUND AND PURPOSE: To identify the contents of a documentation template in The Guide to Physical Therapist Practice using the International Classification of Functioning, Disability, and Health (ICF) Core Sets for rheumatoid arthritis, osteoarthritis, and low back pain (LBP) as reference. METHODS: Concepts were identified from items of an outpatient documentation template and mapped to the ICF using established linking rules. The ICF categories that were linked were compared with existing arthritis and LBP Core Sets. RESULTS: Based on the ICF, the template had the highest number (29%) of linked categories under Activities and participation while Body structures had the least (17%). ICF categories in the arthritis and LBP Core Sets had a 37-55% match with the ICF categories found in the template. We found 164 concepts that were not classified or not defined and 37 as personal factors. CONCLUSIONS: The arthritis and LBP Core Sets were reflected in the contents of the template. ICF categories in the Core Sets were reflected in the template (demonstrating up to 55% match). Potential integration of ICF in documentation templates could be explored and examined in the future to enhance clinical encounters and multidisciplinary communication. PMID- 20306457 TI - Life stories of people with rheumatoid arthritis who retired early: how gender and other contextual factors shaped their everyday activities, including paid work. AB - OBJECTIVE: The aim of the present study was to explore how contextual factors affect the everyday activities of women and men with rheumatoid arthritis (RA), as evident in their life stories. METHODS: Fifteen people with RA, who had retired early due to the disease, were interviewed up to three times, according to a narrative biographic interview style. The life stories of the participants, which were reconstructed from the biographical data and from the transcribed 'told story' were analysed from the perspective of contextual factors, including personal and environmental factors. The rigour and accuracy of the analysis were enhanced by reflexivity and peer-review of the results. RESULTS: The life stories of the participants in this study reflected how contextual factors (such as gender, the healthcare system, the support of families and social and cultural values) shaped their everyday activities. In a society such as in Austria, which is based on traditional patriarchal values, men were presented with difficulties in developing a non-paid-work-related role. For women, if paid work had to be given up, they were more likely to engage in alternative challenging activities which enabled them to develop reflective skills, which in turn contributed to a positive and enriching perspective on their life stories. Health professionals may thus use some of the women's strategies to help men. CONCLUSION: Interventions by health professionals in people with RA may benefit from an approach sensitive to personal and environmental factors. PMID- 20306458 TI - The impact of rapid aneuploidy detection (RAD) in addition to karyotyping versus karyotyping on maternal quality of life. AB - OBJECTIVE: To assess the impact of rapid aneuploidy detection (RAD) combined with fetal karyotyping versus karyotyping only on maternal anxiety and health-related quality of life. METHODS: Women choosing to undergo amniocentesis were selected into group 1, i.e. receiving a karyotype result only (n = 132) or to group 2, i.e. receiving both the result of RAD and karyotyping (n = 181). RESULTS: There were no systematic differences in time of RAD combined with karyotyping versus karyotyping only in terms of anxiety (P = 0.91), generic physical health (P = 0.76, P = 0.46), generic mental health (P = 0.52, P = 0.72), personal perceived control (P = 0.91) and stress (P = 0.13). RAD combined with karyotyping reduced anxiety and stress two weeks earlier compared to karyotyping only. CONCLUSION: RAD as add-on to karyotyping reduces anxiety and stress in the short term but it does not influence overall anxiety, stress, personal perceived control, and generic mental and physical health when compared to a karyotype-only strategy. PMID- 20306459 TI - A new methodology to preserve the original proportion and integrity of cell-free fetal DNA in maternal plasma during sample processing and storage. AB - OBJECTIVE: To develop a standardized blood collection device that preserves fetal cell-free DNA and minimizes the cell-free DNA background in maternal plasma. METHODS: Blood samples were drawn from healthy pregnant donors into K(3)EDTA (BD vacutainer) and Cell-free DNA BCT tubes (Streck, Inc.) and kept at ambient temperature. Plasma was separated by centrifugation and cell-free DNA was extracted. Cell-free DNA from plasma was quantified by quantitative real-time polymerase chain reaction. RESULTS: Blood drawn into Cell-free DNA BCT tubes showed no change in the original proportion of fetal cell-free DNA during a 14 day storage period at ambient temperature. Conversely, maternal blood drawn into K(3)EDTA tubes showed a steady reduction in the original proportion of fetal cell free DNA over the same time period. Using maternal plasma stored in Cell-free DNA BCT tubes for 14 days, fetal cell-free DNA was amplified 80-fold using whole genome amplification (WGA). CONCLUSION: Using Streck's Cell-free DNA BCT tubes, it is possible to preserve the original proportion of fetal cell-free DNA for extended times as well as minimize the post-sampling maternal cell-free DNA background. Preserved in this way, fetal cell-free DNA can be amplified by WGA technology to be used in prenatal diagnostic tests. PMID- 20306460 TI - Prenatal diagnosis of autosomal dominant hereditary spastic paraplegia (SPG42) caused by SLC33A1 mutation in a Chinese kindred. PMID- 20306461 TI - A quantitative model for mRNA translation in Saccharomyces cerevisiae. AB - Messenger RNA (mRNA) translation is an essential step in eukaryotic gene expression that contributes to the regulation of this process. We describe a deterministic model based on ordinary differential equations that describe mRNA translation in Saccharomyces cerevisiae. This model, which was parameterized using published data, was developed to examine the kinetic behaviour of translation initiation factors in response to amino acid availability. The model predicts that the abundance of the eIF1-eIF3-eIF5 complex increases under amino acid starvation conditions, suggesting a possible auxiliary role for these factors in modulating translation initiation in addition to the known mechanisms involving eIF2. Our analyses of the robustness of the mRNA translation model suggest that individual cells within a randomly generated population are sensitive to external perturbations (such as changes in amino acid availability) through Gcn2 signalling. However, the model predicts that individual cells exhibit robustness against internal perturbations (such as changes in the abundance of translation initiation factors and kinetic parameters). Gcn2 appears to enhance this robustness within the system. These findings suggest a trade-off between the robustness and performance of this biological network. The model also predicts that individual cells exhibit considerable heterogeneity with respect to their absolute translation rates, due to random internal perturbations. Therefore, averaging the kinetic behaviour of cell populations probably obscures the dynamic robustness of individual cells. This highlights the importance of single-cell measurements for evaluating network properties. PMID- 20306462 TI - Mandibular dimensions and growth in 11- to 26-week-old Danish fetuses studied by 3D ultrasound. AB - OBJECTIVE: To present normative data on prenatal mandibular morphology and growth. MATERIAL AND METHODS: Fifty-four normal fetuses (Danish Caucasian) were included in the study (gestational age: 11-26 weeks). Fetuses were scanned using a GE Voluson 730 Expert 3D scanner. Scans were visualized and analyzed using GE 4DVIEW software. Mandibular dimensions [base length (B), ramus height (H), and total length (L)] and the mandibular angle (phi) were measured, and the mandibular index was calculated. Method error was estimated by duplicate measurements. Growth was calculated by regressing measured variables on age. RESULTS: Mandibular measurements were found to be reliable [precision: 0.5-1.2 mm (1SD)]. Mean mandibular variable values at week 11: B = 5.2 +/- 2.5 mm; H = 2.7 +/- 1.3 mm; L = 7.7 +/- 3.2 mm; phi = 149 +/- 6.0 degrees; and at week 26: B = 22.6 +/- 2.5 mm; H = 12.3 +/- 1.3 mm; L = 33.1 +/- 3.2 mm; phi = 135 +/- 6.0 degrees. A linear model described growth (B(g)/H(g)/L(g)/phi(g)) giving B(g) = 1.2; H(g) = 0.64; L = 1.7 mm/week; phi(g) = - 0.9 degrees/week. CONCLUSION: Normative 3D data values for the human mandible in 11- to 26-week-old fetuses were presented. All measured mandibular parameters could be described using a linear increasing model from 11 to 26 weeks. All linear dimensions increased in size, while the mandibular angle decreased steadily during the observation period. PMID- 20306463 TI - Distributions of current and new first-trimester Down syndrome screening markers in twin pregnancies. AB - OBJECTIVES: To study the distributions of pregnancy-associated plasma protein A (PAPP-A), the free beta subunit of human chorion gonadotrophin (fbeta-hCG), A Disintegrin and Metalloprotease 12 (ADAM12) and Placental Protein 13 (PP13) in first trimester twin pregnancies. METHODS: Serum marker concentrations were measured in monochorionic and dichorionic twin pregnancies and singleton controls to study differences in multiples of the gestation-specific normal medians (MoMs). RESULTS: Median PAPP-A and fbeta-hCG MoMs were 2.03 and 1.87 for monochorionic twins (n = 116) and 2.18 and 1.89 for dichorionic twins (n = 650). Furthermore, ADAM12 and PP13 MoMs were 1.66 and 1.56 for monochorionic twins (n = 51) and 1.64 and 1.53 for dichorionic twins (n = 249). No statistically significant differences between monochorionic and dichorionic twin pregnancies were found. Correlations between markers in these pregnancies did not differ from singletons. CONCLUSION: For first-trimester screening, different parameters for monochorionic and dichorionic twin pregnancies is not necessary. Furthermore, if ADAM12 and PP13 will be adopted as screening markers, the presented median MoM values, standard deviations and correlation coefficients for twin pregnancies may contribute to a proper twin risk estimation. PMID- 20306464 TI - Characterizing the clinical practice and professional behaviour of rheumatology nurse specialists: a pilot study. AB - BACKGROUND: There is a need to characterize the practice of nurse specialists, for several reasons: to identify the skills and knowledge required for the role, to safeguard the role and to facilitate appropriate remuneration of activities. OBJECTIVE: To develop an instrument, which characterizes the clinical and professional activities of rheumatology nurse specialists (RNSs). METHODS: A questionnaire was produced, informed by the Nursing and Midwifery Council (NMC), to assess competencies in advanced nursing practice and completed by senior clinical rheumatology nurses in the UK undertaking an MSc in rheumatology nursing. Consenting respondents were also interviewed, to enable triangulation of the data. RESULTS: A 38-item questionnaire was produced. It comprised four sections: clinical activities, non-patient-based activities, professional behaviour and perceived confidence in a number of areas of practice. Thirteen nurses completed the questionnaire and seven of these took part in a telephone interview. All RNSs were engaged in the follow-up care of patients with rheumatoid arthritis, providing education, psychological support, monitoring and changing of drug treatments, and referrals to other health professionals. The RNSs produced guidelines, conducted audits and provided mentorship. They had low levels of confidence in seeing new patients, presenting the results of an audit at a conference, and writing a business case. CONCLUSIONS: We have begun the process of developing a questionnaire that can identify the clinical activities, perceived self-competence and professional behaviour of RNSs. This method of characterizing advanced nursing practice offers potential as a model for nurse specialists in other disciplines. Further work is required to validate the questionnaire on a large cohort of RNSs. PMID- 20306465 TI - Optimal suppression of protein phosphatase 2A activity is critical for maintenance of human embryonic stem cell self-renewal. AB - The self-renewal of embryonic stem cells involves a balance between processes governed by crosstalk between intrinsic and extrinsic factors. We hypothesized that protein serine/threonine phosphatase 2A (PP2A) may play a central role in the signaling pathways that regulate human embryonic stem cell (hESC) self renewal. Biochemical analyses revealed that PP2A activity gradually increases over the course of hESC differentiation; PP2A/C and PP2A/A levels also increased. The overexpression of PP2A/C or the addition of PP2A activator C2-ceramide promoted hESC differentiation. Accordingly, the addition of PP2A inactivator okadaic acid (OA) maintained hESC self-renewal in the absence of basic fibroblast growth factor (bFGF). The hESCs maintained with OA expressed pluripotency markers and exhibited substantial telomerase activity with normal karyotypes. The hESCs were able to differentiate into derivatives of the three germ layers, both in vitro and in vivo. Furthermore, the addition of OA and bFGF enabled the maintenance of hESC self-renewal without feeder cells, even in chemically defined xeno-free media. These findings shed a light on the role of PP2A in hESC differentiation and provide a novel strategy for maintaining the self-renewal capability of hESC in bFGF-free, feeder cell-free, and xeno-free media through the optimal suppression of PP2A activity using OA. PMID- 20306466 TI - Helminth-induced CD19+CD23hi B cells modulate experimental allergic and autoimmune inflammation. AB - Numerous population studies and experimental models suggest that helminth infections can ameliorate immuno-inflammatory disorders such as asthma and autoimmunity. Immunosuppressive cell populations associated with helminth infections include Treg and alternatively-activated macrophages. In previous studies, we showed that both CD4(+)CD25(+) Treg, and CD4(-) MLN cells from Heligmosomoides polygyus-infected C57BL/6 mice were able to transfer protection against allergic airway inflammation to sensitized but uninfected animals. We now show that CD4(-)CD19(+) MLN B cells from infected, but not naive, mice are able to transfer a down-modulatory effect on allergy, significantly suppressing airway eosinophilia, IL-5 secretion and pathology following allergen challenge. We further demonstrate that the same cell population can alleviate autoimmune mediated inflammatory events in the CNS, when transferred to uninfected mice undergoing myelin oligodendrocyte glycoprotein((p35-55))-induced EAE. In both allergic and autoimmune models, reduction of disease was achieved with B cells from helminth-infected IL-10(-/-) donors, indicating that donor cell-derived IL 10 is not required. Phenotypically, MLN B cells from helminth-infected mice expressed uniformly high levels of CD23, with follicular (B2) cell surface markers. These data expand previous observations and highlight the broad regulatory environment that develops during helminth infections that can abate diverse inflammatory disorders in vivo. PMID- 20306467 TI - Identification of the rat NKG2D ligands, RAE1L and RRLT, and their role in allograft rejection. AB - NKG2D is a receptor expressed by NK cells and subsets of T lymphocytes. On NK cells, NKG2D functions as a stimulatory receptor that induces effector functions. We cloned and expressed two rat NKG2D ligands, both members of the RAE1 family, RAE1L and RRLT, and demonstrate that these ligands can induce IFN-gamma secretion and cytotoxicity by rat NK cells. To examine changes in expression of NKG2D and the NKG2D ligands RAE1L and RRLT after transplantation, we used a Dark Agouti (DA)-->Lewis rat model of liver transplantation. NKG2D expression was significantly increased in allogeneic liver grafts by day 7 post-transplant. Ligands of NKG2D, absent in normal liver, were readily detected in both syngeneic and allogeneic liver grafts by day 1 post-transplant. By day 7 post-transplant, hepatocyte RAE1L and RRLT expression was significantly and specifically increased in liver allografts. In contrast to acute rejection that develops in the DA- >Lewis model, transplantation of Lewis livers into DA recipients (Lewis-->DA) results in spontaneous tolerance. Interestingly, expression of RAE1L and RRLT is low in Lewis-->DA liver allografts, but significantly increased in DA-->Lewis liver allografts undergoing rejection. In conclusion, our results suggest that expression of NKG2D ligands may be important in allograft rejection. PMID- 20306468 TI - CD8+ NK cells are predominant in chimpanzees, characterized by high NCR expression and cytokine production, and preserved in chronic HIV-1 infection. AB - HIV-1 infection in humans results in an early and progressive NK cell dysfunction and an accumulation of an "anergic" CD56- CD16+ NK subset, which is characterised by low natural cytotoxicity receptor expression and low cytokine producing capacity. In contrast to humans, chimpanzee NK cells do not display a distinguishable CD56(bright) and CD56(dim) subset but, as shown here, could be subdivided into functionally different CD8+ and CD8- subsets. The CD8+ NK cells expressed significantly higher levels of triggering receptors including NKp46 and, upon in vitro activation, produced more IFN-gamma, TNF-alpha and CD107 than their CD8- counterparts. In addition, chimpanzee CD8- NK cells had relatively high levels of HLA-DR expression, suggestive of an activated state. Killing inhibitory receptors were expressed only at low levels; however, upon in vitro stimulation, they were up-regulated in CD8+ but not in CD8- NK cells and were functionally capable of inhibiting NKp30-triggered killing. In contrast to HIV-1 infected humans, infected chimpanzees maintained their dominant CD8+ NK cell population, with high expression of natural cytotoxicity receptors. PMID- 20306469 TI - The CD4+ T-cell epitope-binding register is a critical parameter when generating functional HLA-DR tetramers with promiscuous peptides. AB - Detection of CD4(+) T cells specific for tumor-associated antigens is critical to investigate the spontaneous tumor immunosurveillance and to monitor immunotherapy protocols in patients. We investigated the ability of HLA-DR 1101 multimers to detect CD4(+) T cells specific for three highly promiscuous MAGE-A3 derived peptides: MAGE-A3(191-205) (p39), MAGE-A3(281-295) (p57) and MAGE-A3(286-300) (p58). Tetramers stained specific CD4(+) T cells only when loaded with p39, although all peptides activated the specific T cells when presented by plastic bound HLA-DR 1101 monomers. This suggested that tetramer staining ability was determined by the mode rather than the affinity of peptide binding to HLA-DR 1101. We hypothesized that peptides should bear a single P1 anchor residue to bind all arms of the multimer in a homogeneous register to generate peptide-HLA DR conformers with maximal avidity. Bioinformatics analysis indicated that p39 contained one putative P1 anchor residue, whereas the other two peptides contained multiple ones. Designing p57 and p58 analogues containing a single anchor residue generated HLA-DR 1101 tetramers that stained specific CD4(+) T cells. Producing HLA-DR 1101 monomers linked with the optimized MAGE-A3 analogues, but not with the original epitopes, further improved tetramer efficiency. Optimization of CD4(+) T-cell epitope-binding registers is thus critical to generate functional HLA-DR tetramers. PMID- 20306470 TI - Direct visualization of the dynamics of antigen presentation in human cells infected with cytomegalovirus revealed by antibodies mimicking TCR specificity. AB - There are no direct means to study class I MHC presentation in human normal or diseased cells. Using CMV-infected human cells and applying novel mAb that mimic T-cell receptor specificity directed toward the immunogenic epitope of the viral pp65 protein presented on HLA-A2 molecules, we directly imaged the dynamics of Ag presentation in infected cells. We demonstrate that following infection large intracellular pools of HLA-A2/pp65 complexes are localized to the Golgi. These HLA-A2/pp65 pools account for the majority of total HLA-A2 molecules in infected cells. Interestingly, these large pools are sequestered inside infected cells and only a small portion of them are exported to the cell surface. Virus-induced class I MHC down-regulation did not affect the intracellular pool of HLA-A2/pp65 complexes. Our data also suggest that proteasome function influences the release of class I complexes to the membrane. We present herein a new and direct molecular tool to study the dynamics of viral Ag presentation that may further elucidate the balance between immune response versus viral escape. PMID- 20306471 TI - Divergent roles of Toll-like receptor 2 in response to lipoteichoic acid and Staphylococcus aureus in vivo. AB - The response of leukocytes to lipoteichoic acid (LTA), a TLR2-dependent major cell wall component of Staphylococcus aureus, is linked to the outcome of an infection. In this study we investigated the role of nonhematopoietic TLR2 in response to LTA and S. aureus by creating bone marrow chimeras. Significant leukocyte recruitment in response to LTA required IFN-gamma priming in WT C57BL/6 and TLR2(-/-)-->WT mice, but was not observed in TLR2(-/-) or WT-->TLR2(-/-) animals. LTA also induced a proinflammatory response in IFN-gamma primed primary human microvascular endothelial cells leading to leukocyte recruitment in vitro. When mice were infected with S. aureus, the most profound elevation of TNF-alpha and IL-6 was seen in TLR2(-/-) and TLR2(-/-)-->WT mice. TLR2(-/-), but not chimeric mice, demonstrated increased IL-17, blood leukocytosis and pulmonary neutrophilia compared to WT mice. Collectively, the results suggest an essential role for IFN-gamma and nonhematopoietic TLR2 for leukocyte recruitment in response to LTA. In contrast, TLR2 on both hematopoietic and nonhematopoietic cells appears to orchestrate an inhibitory response to S. aureus such that in complete TLR2 deficiency, there is an exaggerated proinflammatory response and/or skewing of the immune response towards a Th17 phenotype that may contribute to the decreased survival of TLR2(-/-) mice. PMID- 20306472 TI - SARM inhibits both TRIF- and MyD88-mediated AP-1 activation. AB - SARM (sterile alpha- and armadillo-motif-containing protein), the fifth identified TIR (Toll-interleukin 1 receptor (IL-1R)) domain-containing adaptors in humans, downregulates NF-kappaB and IRF3 (interferon-regulatory factor 3) mediated TLR3 and TLR4 signaling. SARM was characterized as a negative regulator of the TRIF (TIR-domain-containing adaptor protein inducing IFN-beta)-dependent pathway via its interaction with TRIF. However, the precise mechanism of action of SARM remains unclear. Here, we demonstrate that SARM inhibits MAPK activation in human embryonic kidney 293 cells, and U937 cells. Both the TRIF- and MyD88 mediated, as well as basal MAPK activity, were repressed, indicating that SARM mediated inhibition may not be exclusively directed at TRIF or MyD88, but that SARM may also directly inhibit MAPK phosphorylation. The MAPK inhibition effect was verified by RNAi, which increased the basal level of AP-1. Furthermore, LPS challenge upregulated SARM at both the mRNA and protein levels. Finally, we provide evidence to show that truncated SARM changes its subcellular localization, suggesting the importance of the N-terminal and sterile alpha motif domains in the autoregulation of SARM activity. PMID- 20306474 TI - Effects of enzymatic hydrolysis on lentil allergenicity. AB - Enzymatic hydrolysis and further processing are commonly used to produce hypoallergenic dietary products derived from different protein sources, such as cow's milk. Lentils and chickpeas seem to be an important cause of IgE-mediated hypersensitivity in the Mediterranean area and India. Some studies have investigated the effects of enzymatic treatments on the in vitro immunological reactivity of members of the Leguminosae family, such as soybean, chickpea, lentil, and lupine. Nevertheless, there are only a few studies carried out to evaluate the effect on IgE reactivity of these food-hydrolysis products with sera from patients with well-documented allergy to these foods. In this study, lentil protein extract was hydrolyzed by sequential action of an endoprotease (Alcalase) and an exoprotease (Flavourzyme). Immunoreactivity to raw and hydrolyzed lentil extract was evaluated by means of IgE immunoblotting and ELISA using sera from five patients with clinical allergy to lentil. The results indicated that sequential hydrolysis of lentil results in an important proteolytic destruction of IgE-binding epitopes shown by in vitro experiments. However, some allergenic proteins were still detected by sera from four out of five patients in the last step of sequential hydrolyzation. PMID- 20306473 TI - Chromium dinicocysteinate supplementation can lower blood glucose, CRP, MCP-1, ICAM-1, creatinine, apparently mediated by elevated blood vitamin C and adiponectin and inhibition of NFkappaB, Akt, and Glut-2 in livers of zucker diabetic fatty rats. AB - Chromium and cysteine supplementation can improve glucose metabolism in animal studies. This study examined the hypothesis that a cysteinate complex of chromium is significantly beneficial than either of them in lowering blood glucose and vascular inflammation markers in Zucker diabetic fatty (ZDF) rats. Starting at the age of 6 wk, ZDF rats were supplemented orally (daily gavages for 8 more weeks) with saline-placebo (D) or chromium (400 microg Cr/Kg body weight) as chromium dinicocysteinate (CDNC), chromium dinicotinate (CDN) or chromium picolinate (CP) or equimolar L-cysteine (LC, img/Kg body weight), and fed Purina 5008 diet for 8 wk. ZDF rats of 6 wk age before any supplementations and onset of diabetes were considered as baseline. D rats showed elevated levels of fasting blood glucose, HbA(1), CRP, MCP-1, ICAM-1 and oxidative stress (lipid peroxidation) and lower adiponectin and vitamin C, when compared with baseline rats. In comparison to D group, CDNC group had significantly lower blood glucose, HbA(1), CRP, MCP-1, ICAM-1 and lipid peroxidation and increased vitamin C and adiponectin levels. CDN, CP or LC showed significantly less or no effect on these biomarkers. Only CDNC lowered blood creatinine levels in comparison to D. While CDN and CP had no effect, activation of NFkappaB, Akt and glucose transporter-2 levels were decreased, insulin receptor substrate 1 (IRS-1) activation increased in livers of CDNC-rats. CDNC effect on glycemia, NFkappaB, Akt and IRS-1 in liver was significantly greater compared with LC. Blood chromium levels did not differ between Cr-groups. Exogenous vitamin C supplementation significantly inhibited MCP-1 secretion in U937 monocytes cultured in high-glucose-medium. CDNC is a potent hypoglycemic compound with anti-inflammatory activity apparently mediated by elevated blood vitamin C and adiponectin and inhibition of NFkappaB, Akt, and Glut-2 and increased IRS-1 activation in livers of type 2 diabetic rats. PMID- 20306475 TI - Sesamin attenuates intercellular cell adhesion molecule-1 expression in vitro in TNF-alpha-treated human aortic endothelial cells and in vivo in apolipoprotein-E deficient mice. AB - Sesame lignans have antioxidative and anti-inflammatory properties. We focused on the effects of the lignans sesamin and sesamol on the expression of endothelial leukocyte adhesion molecules in tumor necrosis factor-alpha (TNF-alpha)-treated human aortic endothelial cells (HAECs). When HAECs were pretreated with sesamin (10 or 100 microM), the TNF-alpha-induced expression of intercellular cell adhesion molecule-1 (ICAM-1) was significantly reduced (35 or 70% decrease, respectively) by Western blotting. Sesamol was less effective at inhibiting ICAM 1 expression (30% decrease at 100 microM). Sesamin and sesamol reduced the marked TNF-alpha-induced increase in human antigen R (HuR) translocation and the interaction between HuR and the 3'UTR of ICAM-1 mRNA. Both significantly reduced the binding of monocytes to TNF-alpha-stimulated HAECs. Sesamin significantly attenuated TNF-alpha-induced ICAM-1 expression and cell adhesion by downregulation of extracellular signal-regulated kinase 1/2 and p38. Furthermore, in vivo, sesamin attenuated intimal thickening and ICAM-1 expression seen in aortas of apolipoprotein-E-deficient mice. Taken together, these data suggest that sesamin inhibits TNF-alpha-induced extracellular signal-regulated kinase/p38 phosphorylation, nuclear translocation of NF-kappaB p65, cytoplasmic translocalization of HuR and thereby suppresses ICAM-1 expression, resulting in reduced adhesion of leukocytes. These results also suggest that sesamin may prevent the development of atherosclerosis and inflammatory responses. PMID- 20306476 TI - Vitamin D-mediated calcium absorption in patients with clinically stable Crohn's disease: a pilot study. AB - Vitamin D is the critical hormone for intestinal absorption of calcium. Optimal calcium absorption is important for proper mineralization of bone in the prevention of osteoporosis and osteoporotic fractures, among other important functions. Diseases associated with gut inflammation, such as Crohn's disease (CD), may impair calcium absorption. This pilot study evaluated vitamin D- dependent calcium absorption in subjects with CD. Male subjects with CD (n=4) and healthy age-matched controls (n=5) were studied. All subjects had fractional calcium absorption (FCA; by the dual calcium isotope method), serum 25 hydroxyvitamin D, serum calcium and 24 h urinary calcium excretion measurements at baseline. The FCA in response to vitamin D therapy was re-assessed following administration of oral calcitriol 0.25 mcg twice daily for 1 wk, followed by oral calcitriol 0.50 mcg twice daily for 1 wk. Serum calcium and 24 h urinary calcium determinations were re-assessed after each increasing dose of calcitriol as safety measures. There was no significant difference in calcium FCA at baseline or after increasing doses of calcitriol between the CD and controls. FCA in the control and CD group was approximately 35% at baseline, which increased to 60% after calcitriol therapy. No subject developed hypercalcemia or hypercalciuria. Our results suggest that CD patients have a normal response to vitamin D in enhancing the efficacy of calcium absorption. This suggests that stable CD patients can follow calcium and vitamin D guidelines of non-CD adults. Other factors independent of vitamin D status may impair intestinal calcium absorption in CD, including the degree and location of inflammation, presence of surgical resection and/or use of glucocorticoids. PMID- 20306477 TI - Tocotrienols activity in MCF-7 breast cancer cells: involvement of ERbeta signal transduction. AB - The term Vitamin E is utilized to describe eight molecules, subdivided into two groups, tocopherols and tocotrienols (TTs). It has been shown that specific TTs affect the growth of several lines of tumour cells, and that this activity is not shared by tocopherols. In agreement with these observations, a TTs-rich fraction from palm oil (PTRF) was reported to inhibit proliferation and induce apoptosis in several cancer cells. However, the molecular mechanism involved in TTs activity is still unclear. We have recently proposed that TTs pro-apoptotic activity involves estrogen receptor beta (ERbeta) signalling. In this study, we report that, in MCF-7 breast cancer cell, expressing both ERalpha and ERbeta, PTRF treatment increases ERbeta nuclear translocation, as demonstrated by immunofluorescence experiments and significantly inhibits ERalpha expression ( 458.91-fold of change) and complete disappearing of the protein from the nucleus. Moreover, PTRF treatment induces ER-dependent genes expression (macrophage inhibitory cytokine-1, early growth response-1 and Cathepsin D) which is inhibited by the ER inhibitor, ICI 182.780, and induces DNA fragmentation. Finally, cDNA-array experiments suggest that the activation of specific pathways in cells treated with gamma-TT with respect to alpha-TT. Our data suggest a novel potential molecular mechanism for TTs activity. PMID- 20306478 TI - Dietary phenolic acids attenuate multiple stages of protein glycation and high glucose-stimulated proinflammatory IL-1beta activation by interfering with chromatin remodeling and transcription in monocytes. AB - This study examined the effects of dietary phenolic acids on individual stages of protein glycation and utilized monocyte cultures to assess whether these phytochemicals modulate the activation of proinflammatory cytokine under high glucose (HG, 15 mmol/L) conditions mimicking diabetes. In vitro glycation assays showed that a number of phenolic acids exerted inhibitory effects on the glycation reaction and its subsequent crosslinking. Phenolic acids, especially methoxyphenolic acids, prevented increase in both levels of the interleukin-1beta (IL-1beta) and oxidative stress caused by HG. The effect appeared to be mediated by modulation of the protein kinase C/nuclear factor-kappaB axis. Chromatin immunoprecipitation demonstrated for the first time that HG increased the recruitment of nuclear factor-kappaB p65 and CREB-binding protein to the IL-1beta promoter. Interestingly, HG also increased histone acetylation and methylation within the IL-1beta promoter and decreased histone deacetylase activities in monocytes, thus facilitating chromatin remodeling and transcription. Such inappropriate inflammatory responses were found to be controlled effectively by treatment with methoxyphenolic compounds. In conclusion, this study suggests that phenolic acids could exert their anti-inflammatory activities as antiglycation agents and as modifiers of signaling pathways. It provides evidence for a novel mechanism by which phenolics supplementation might have additional protective effects against diabetic complications. PMID- 20306479 TI - Monocarboxylate transporter 1 and CD147 are up-regulated by natural and synthetic peroxisome proliferator-activated receptor alpha agonists in livers of rodents and pigs. AB - Monocarboxylate transporter (MCT)-1 mediates the transport of ketone bodies and other monocarboxylic acids across the plasma membrane. MCT1 is up-regulated by peroxisome proliferator-activated receptor (PPAR)-alpha, a transcription factor that mediates the adaptive response to fasting by up-regulation of genes involved in fatty acid oxidation and ketogenesis. Here, we show for the first time that MCT1 is up-regulated by dietary natural PPAR-alpha agonists. Both, an oxidized fat and conjugated linoleic acids increased MCT1 mRNA concentration in the liver of rats. Also, in the liver of pigs as non-proliferating species MCT1 was up regulated upon PPAR-alpha activation by clofibrate, oxidized fat and fasting. Concomitant with up-regulation of MCT1, mRNA level of CD147 was increased in livers of rats and pigs. CD147 is a plasma membrane glycoprotein that is required for translocation and transport activity of MCT1. CD147 mRNA increase upon PPAR alpha activation could not be observed in mice lacking PPAR-alpha, which also fail in up-regulation of MCT1 indicating a co-regulation of MCT1 and CD147. Analysis of the 5'-flanking region of mouse MCT1 gene by reporter gene assay revealed that promoter activity of mouse MCT1 was not induced by PPAR-alpha, indicating that the 5'-flanking region is not involved in MCT1 regulation by PPAR alpha. PMID- 20306482 TI - High-throughput proteomics and bioinformatics: joined at the hip. PMID- 20306480 TI - Structure-affinity relationship of flavones on binding to serum albumins: effect of hydroxyl groups on ring A. AB - Four flavones (flavone, 7-hydroxyflavone, chrysin, and baicalein) sharing the same B- and C-ring structure but a different numbers of hydroxyl groups on the A ring were studied for their affinities for BSA and HSA. The hydroxylation on ring A of flavones increased the binding constants (K(a)) and the number of binding sites (n) between flavones and serum albumins. The affinities of 7-hydroxyflavone for BSA and HSA were about 800 times and 40 times higher than that of flavone, respectively. It appears that the optimal number of hydroxyl groups introduced to the ring A of flavones is one. As more hydroxyl groups were introduced to positions at C-5, C-6, and/or C-7 of flavones, the affinities for serum albumins decrease. The critical energy transfer distances (R(0)) between the hydroxylated flavones (1-3 OH on the ring A) and serum albumins decreased with the increasing affinities for serum albumins. PMID- 20306484 TI - A longitudinal analysis of early risk factors for adult-onset offending: What predicts a delayed criminal career? AB - BACKGROUND: Late-onset offending, at the age of 21 or thereafter, is an underexplored dimension of the criminal career. AIMS: Our aims were to explore which factors are precursors of late-onset offending, and the extent to which adult criminality can be predicted in childhood and adolescence. METHOD: This is the first study that defines late-onset offending based on a combination of official records and self-reports. Longitudinal data from the Cambridge Study in Delinquent Development (CSDD) were used. Four hundred and three South London men, followed from ages 8-10 to ages 48-50, were divided into late-starters (LS, n = 51), early-starters (ES, n = 140) and non-offenders (NO, n = 212). RESULTS: LS men were more likely than NO men to have been neurotic, truants or in poor housing at ages 8-10. At ages 12-14, they tended to be neurotic, and at ages 16 18, they had high unemployment and spent time hanging about on the streets. Compared with ES, LS were nervous at ages 8-10, and at age 18 they were more likely to be sexual virgins. Overall, LS men were more similar to NO men before age 21, but more similar to ES men by age 32. CONCLUSIONS: Our hypotheses that late-onset offenders would be particularly characterised by neuroticism or nervousness, but that this would buffer rather than fully protect over the life course, were sustained. Intervention to increase the resilience of children and adolescents who are rated as high on neurotic characteristics may lessen the burden that these factors impose in adult life and reduce the risk of a deteriorating quality of life and late onset criminal careers. PMID- 20306485 TI - Evaluation of tetracationic salts as gas-phase ion-pairing agents for the detection of trivalent anions in positive mode electrospray ionization mass spectrometry. AB - In previous studies, new electrospray ionization mass spectrometry (ESI-MS) approaches were developed for the highly sensitive detection of singly and doubly charged anions in positive mode ESI-MS by using specially synthesized dicationic and tricationic ion-pairing agents, respectively. By detecting the positively charged ion complex in the positive mode, limits of detection (LODs) for the anions can be lowered by several magnitudes. In this work, we used eighteen newly synthesized tetracationic ion-pairing agents, constructed with different geometries, linkages and cation moieties, for the detection of eighteen triply charged anions of different structural motifs. The LODs for these anions were from ten to several thousand times lower in the positive selective ion monitoring (SIM) mode than in the negative mode. These tetracationic agents also were shown to be useful for the detection of -1 and -2 anions. In addition, the LODs for -3 anions can be further lowered by monitoring the product fragments of the ion pairing complexes in the single reaction monitoring (SRM) mode. PMID- 20306487 TI - Reactive oxygen radical scavengers--saving the cells? PMID- 20306490 TI - Backbone additivity in the transfer model of protein solvation. AB - The transfer model implying additivity of the peptide backbone free energy of transfer is computationally tested. Molecular dynamics simulations are used to determine the extent of change in transfer free energy (DeltaG(tr)) with increase in chain length of oligoglycine with capped end groups. Solvation free energies of oligoglycine models of varying lengths in pure water and in the osmolyte solutions, 2M urea and 2M trimethylamine N-oxide (TMAO), were calculated from simulations of all atom models, and DeltaG(tr) values for peptide backbone transfer from water to the osmolyte solutions were determined. The results show that the transfer free energies change linearly with increasing chain length, demonstrating the principle of additivity, and provide values in reasonable agreement with experiment. The peptide backbone transfer free energy contributions arise from van der Waals interactions in the case of transfer to urea, but from electrostatics on transfer to TMAO solution. The simulations used here allow for the calculation of the solvation and transfer free energy of longer oligoglycine models to be evaluated than is currently possible through experiment. The peptide backbone unit computed transfer free energy of -54 cal/mol/M compares quite favorably with -43 cal/mol/M determined experimentally. PMID- 20306491 TI - Design, selection, and characterization of a split chorismate mutase. AB - Split proteins are versatile tools for detecting protein-protein interactions and studying protein folding. Here, we report a new, particularly small split enzyme, engineered from a thermostable chorismate mutase (CM). Upon dissecting the helical-bundle CM from Methanococcus jannaschii into a short N-terminal helix and a 3-helix segment and attaching an antiparallel leucine zipper dimerization domain to the individual fragments, we obtained a weakly active heterodimeric mutase. Using combinatorial mutagenesis and in vivo selection, we optimized the short linker sequences connecting the leucine zipper to the enzyme domain. One of the selected CMs was characterized in detail. It spontaneously assembles from the separately inactive fragments and exhibits wild-type like CM activity. Owing to the availability of a well characterized selection system, the simple 4-helix bundle topology, and the small size of the N-terminal helix, the heterodimeric CM could be a valuable scaffold for enzyme engineering efforts and as a split sensor for specifically oriented protein-protein interactions. PMID- 20306492 TI - Crystal structure of the C-terminal domain of the Salmonella type III secretion system export apparatus protein InvA. AB - InvA is a prominent inner-membrane component of the Salmonella type III secretion system (T3SS) apparatus, which is responsible for regulating virulence protein export in pathogenic bacteria. InvA is made up of an N-terminal integral membrane domain and a C-terminal cytoplasmic domain that is proposed to form part of a docking platform for the soluble export apparatus proteins notably the T3SS ATPase InvC. Here, we report the novel crystal structure of the C-terminal domain of Salmonella InvA which shows a compact structure composed of four subdomains. The overall structure is unique although the first and second subdomains exhibit structural similarity to the peripheral stalk of the A/V-type ATPase and a ring building motif found in other T3SS proteins respectively. PMID- 20306493 TI - Dimer-monomer equilibrium of human thymidylate synthase monitored by fluorescence resonance energy transfer. AB - An ad hoc bioconjugation/fluorescence resonance energy transfer (FRET) assay has been designed to spectroscopically monitor the quaternary state of human thymidylate synthase dimeric protein. The approach enables the chemoselective engineering of allosteric residues while preserving the native protein functions through reversible masking of residues within the catalytic site, and is therefore suitable for activity/oligomerization dual assay screenings. It is applied to tag the two subunits of human thymidylate synthase at cysteines 43 and 43' with an excitation energy donor/acceptor pair. The dimer-monomer equilibrium of the enzyme is then characterized through steady-state fluorescence determination of the intersubunit resonance energy transfer efficiency. PMID- 20306494 TI - The influence of sociodemographic characteristics on agreement between self reports and expert exposure assessments. AB - BACKGROUND: Often in exposure assessment for epidemiology, there are no highly accurate exposure data and different measurement methods are considered. The objective of this study was to use various statistical techniques to explore agreement between individual reports and expert ratings of workplace exposures in several industries and investigate the sociodemographic influences on this agreement. METHODS: A cohort of 1,282 employees at 4 industries/14 worksites answered questions on workplace physical, chemical, and psychosocial exposures over the past 12 months. Occupational hygienists constructed job exposure matrices (JEMs) based on worksite walkthrough exposure evaluations. Worker self reports were compared with the JEMs using multivariable analyses to explore discord. RESULTS: There was poor agreement between the self-reported and expert exposure assessments, but there was evidence that agreement was modified by sociodemographic characteristics. Several characteristics including gender, age, race/ethnicity, hourly wage and nativity strongly affected the degree of discord between self-reports and expert raters across a wide array of different exposures. CONCLUSIONS: Agreement between exposure assessment tools may be affected by sociodemographic characteristics. This study is cross-sectional and therefore, a snapshot of potential exposures in the workplace. Nevertheless, future studies should take into account the social contexts within which workplace exposures occur. PMID- 20306495 TI - Psychosocial work environment and medical symptoms among Swedish commercial airline cabin crew. AB - BACKGROUND: Associations between stress measured by the demands-control model, iso-strain model, and stress-related symptoms among cabin crew were studied. METHODS: A questionnaire about psychosocial work environment and symptoms was answered by 918 (82%) flight attendants, stewards, and pursers at one airline company in 2005. Adjustment was made for age, gender, smoking, job category, and flight length using multiple logistic regression. RESULTS: Weekly headaches, concentration difficulties, fatigue, and gastrointestinal symptoms were reported at rates of 18%, 10%, 56%, and 13%, respectively. Pursers scored higher on control than the others and they had lower associations between the strain measured by the demands-control model and symptoms than stewards and flight attendants. All symptoms were more common in the high strain situation than in the low strain (reference). An active situation was related to an excess of symptoms. Low social support in the iso-strain model increased risk of symptoms. CONCLUSIONS: Demands-control and iso-strain models are useful in studying stress related symptoms in cabin crews. The dimension of social support adds explanatory value. PMID- 20306496 TI - Hazardous task recognition among U.S. adolescents working in the retail or service industry. AB - BACKGROUND: Although the hazardous tasks adolescent workers perform in service and retail industries are well documented, little is known about the extent to which young workers recognize these tasks as hazardous or dangerous. METHODS: Using data from a nationally representative cross-sectional telephone survey conducted in 2003, we examined hazardous task recognition among 858 adolescents working in the retail or service industry. RESULTS: Approximately 13% (n = 123) of respondents reported that they consider at least one of their job tasks to be hazardous or dangerous. Among the respondents who performed tasks known to be hazardous, very few actually recognized these tasks as being hazardous or dangerous. CONCLUSION: Working adolescents appear to underestimate the dangers associated with work, thus increasing the potential likelihood of injury. Emphasis should be placed on eliminating or reducing hazards in the workplace while simultaneously improving young workers' recognition of the hazardous nature of many of the tasks they perform. PMID- 20306497 TI - Single-nucleotide polymorphisms in the p53 pathway genes modify cancer risk in BRCA1 and BRCA2 carriers of Jewish-Ashkenazi descent. AB - Germline mutations in the BRCA1 and BRCA2 genes are associated with a significantly increased lifetime risk for developing breast and/or ovarian cancer. However, incomplete penetrance and substantial variability in age of disease onset among carriers of the same mutation suggests the involvement of additional modifier genes and/or environmental factors. Somatic inactivating mutations in the p53 gene and genes of the p53 pathway often accompany BRCA1/2 associated tumors. Therefore, we assessed whether these genes are modifiers of penetrance. We genotyped Jewish-Ashkenazi women for functional single-nucleotide polymorphisms (SNPs) in the AKT1 (C>T rs3730358) and the PERP (C>T rs2484067) genes that affect p53-mediated apoptosis, as well as two tag-SNPs in the CHEK2 (C>T rs743184) and the ZBRK1/ZNF350 (G>A rs2278414) genes that encode for proteins involved in growth arrest following DNA damage. The study population included 138 healthy women, 148 breast/ovarian cancer BRCA1/2 mutation carriers, 121 asymptomatic BRCA1/2 mutation carriers, and 210 sporadic noncarrier breast cancer patients. Utilizing lambda(2) and Kaplan-Meier analysis revealed a hazard ratio (HR) of 3.23 (95% CI: 1.44-54, P = 0.0184) for the TT genotype of AKT (rs3730358), HR = 2.105 (95% CI: 1.049-7.434, P = 0.039) for CHEK2 CC genotype (rs743184), and HR = 2.4743 (95% CI: 1.205-11.53, P = 0.022) for the AG genotype of ZBRK1/ZNF350 (rs2278414). No significant association between PERP variants and cancer was identified HR = 0.662 (95% CI: 0.289-1.324, P = 0.261). Our results suggest that genes that act upstream of p53, or participate in the DNA damage response, may modify the risk of cancer in women with mutant BRCA1/2 alleles. PMID- 20306498 TI - Elevated glucose induces congenital heart defects by altering the expression of tbx5, tbx20, and has2 in developing zebrafish embryos. AB - BACKGROUND: Maternal diabetes increases the risk of congenital heart defects in infants, and hyperglycemia acts as a major teratogen. Multiple steps of cardiac development, including endocardial cushion morphogenesis and development of neural crest cells, are challenged under elevated glucose conditions. However, the direct effect of hyperglycemia on embryo heart organogenesis remains to be investigated. METHODS: Zebrafish embryos in different stages were exposed to D glucose for 12 or 24 hr to determine the sensitive window during early heart development. In the subsequent study, 6 hr post-fertilization embryos were treated with either 25 mmol/liter D-glucose or L-glucose for 24 hr. The expression of genes was analyzed by whole-mount in situ hybridization. RESULTS: The highest incidence of cardiac malformations was found during 6-30 hpf exposure periods. After 24 hr exposure, D-glucose-treated embryos exhibited significant developmental delay and diverse cardiac malformations, but embryos exposed to L glucose showed no apparent phenotype. Further investigation of the origin of heart defects showed that cardiac looping was affected earliest, while the specification of cardiac progenitors and heart tube assembly were complete. Moreover, the expression patterns of tbx5, tbx20, and has2 were altered in the defective hearts. CONCLUSIONS: Our data demonstrate that elevated glucose alone induces cardiac defects in zebrafish embryos by altering the expression pattern of tbx5, tbx20, and has2 in the heart. We also show the first evidence that cardiac looping is affected earliest during heart organogenesis. These research results are important for devising preventive and therapeutic strategies aimed at reducing the occurrence of congenital heart defects in diabetic pregnancy. PMID- 20306499 TI - A possible association of periodontal infectious diseases in pregnant women with isolated orofacial clefts in their children: A population-based case-control study. AB - BACKGROUND: The aim of the study was to check the association of maternal periodontal infectious disease (MPID) during pregnancy and the possible risk for birth outcomes, mainly structural birth defects: congenital abnormalities (CAs) in their children. METHODS: The population-based data set of the Hungarian Case Control Surveillance System of Congenital Abnormalities, 1980-1996, was evaluated. The occurrence of medically recorded MPID in the prenatal maternity logbook was compared in 22,843 cases with different CAs and 38,151 matched controls without defects. RESULTS: Twenty-one case mothers who had offspring with a CA (case group) and 17 pregnant women who delivered newborn infants without a CA (control group) had an MPID. However, of 21 cases, 6 had isolated cleft lip +/ palate (OR with 95% CI: 10.7, 4.2-27.3), and 2 were affected with isolated cleft palate (7.9, 1.8-34.2). Of these 8 cases, 6 had mothers with the exposure of MPID in the critical period of these orofacial clefts, 7 mothers were visited at home, and 6 were smokers during pregnancy. CONCLUSIONS: The unexpected findings of the study showed a strong association of MPID during pregnancy with a higher risk of isolated orofacial clefts in their children. PMID- 20306500 TI - Importance of the angiosome concept for endovascular therapy in patients with critical limb ischemia. AB - OBJECTIVE: We investigated the role of the angiosome concept in endovascular therapy (EVT) for limb salvage. BACKGROUND: The angiosome concept is clinically useful in bypass surgery for critical limbs ischemia (CLI). However, comparison with direct and indirect flow to the site of ulceration based on angiosome concept regarding freedom from amputation has not been systematically studied for the patient with CLI undergoing EVT. METHODS: We analyzed 203 limbs in 177 consecutive patients (male = 127, age = 70 +/- 11 years) with ischemic ulceration that was Rutherford 5 or 6 (5 in 145 limbs and 6 in 58 limbs; pretreatment ankle brachial index = 0.74 +/- 0.27), who underwent EVT alone without bypass surgery. We classified these patients into direct and indirect groups depending on whether feeding artery flow to the site of ulceration was successfully acquired or not acquired based on the angiosome concept. Freedom from amputation was compared between the direct and the indirect groups by Kaplan-Meier analysis. RESULTS: The overall limb salvage rate was 82% (167/203). Skin perfusion pressure was significantly higher in the direct group (67 +/- 25 mm Hg) than in the indirect group (41 +/- 20 mm Hg, P = 0.002). The limb salvage rate was also significantly (P = 0.03) higher in the direct group (86%) than in the indirect group (69%) for up to 4 years after the procedure. The number of vessels with run-off flow did not influence the limb salvage rate in either the direct group (P = 0.84) or the indirect group (P = 0.90). CONCLUSION: Acquiring direct flow based on the angiosome concept is important for limb salvage by EVT in patients with CLI. PMID- 20306501 TI - Psychobiological models of adolescent risk: implications for prevention and intervention. AB - Psychobiological models of risk have much to contribute to the prevention of and intervention with risky behavior among adolescents. Emerging research is beginning to provide better information about mechanisms underlying individual differences in risky behavior (e.g., differences in self-regulation) and providing insight into unique vulnerabilities that occur during adolescence (e.g., increases in reward seeking). This work suggests ways in which prevention programming can be designed to be sensitive to both individual differences and developmental timing. Psychobiological models of risk also have practical implications for the manner and methods of conducting prevention and intervention work. Future work in both the etiology and prevention of risky behavior can benefit from ongoing dialogue and has the potential to result in a more sophisticated understanding of the mechanisms of change related to risky behavior. . PMID- 20306502 TI - Cell morphology and intracellular ionic homeostasis explored with a multimodal approach combining epifluorescence and digital holographic microscopy. AB - The authors have developed a live-cell multimodality microscope combining epifluorescence with digital holographic microscopy; it has been implemented with a decoupling procedure allowing to separately measure from the quantitative phase important cell parameters including absolute volume, shape and integral intracellular refractive index. In combination with the numerous different specific fluorescent cellular probes, this multimodality microscopy can address important issues in cell biology. This is demonstrated by the study of intracellular calcium homeostasis associated with the change in cell volume, which play a critical role in the excitotoxicity-induced neuronal death. PMID- 20306503 TI - Synthesis, magnetic properties, and STM spectroscopy of cobalt(II) Cubanes [Co(II) (4)(Cl)(4)(HL)(4)]. AB - Reaction of cobalt(II) chloride hexahydrate with N-substituted diethanolamines H(2)L(2-4) (3) in the presence of LiH in anhydrous THF leads under anaerobic conditions to the formation of three isostructural tetranuclear cobalt(II) complexes [Co(II) (4)(Cl)(4)(HL(2-4))(4)] (4) with a [Co(4)(mu(3)-O)(4)](4+) cubane core. According to X-ray structural analyses, the complexes 4 a,c crystallize in the tetragonal space group I4(1)/a, whereas for complex 4 b the tetragonal space group P$?bar 4$ was found. In the solid state the orientation of the cubane cores and the formation of a 3D framework were controlled by the ligand substituents of the cobalt(II) cubanes 4. This also allowed detailed magnetic investigations on single crystals. The analysis of the SQUID magnetic susceptibility data for 4 a gave intramolecular ferromagnetic couplings of the cobalt(II) ions (J(1) approximately 20.4 K, J(2) approximately 7.6 K), resulting in an S=6 ground-state multiplet. The anisotropy was found to be of the easy-axis type (D=-1.55 K) with a resulting anisotropy barrier of Delta approximately 55.8 K. Two-dimensional electron-gas (2DEG) Hall magnetization measurements revealed that complex 4 a is a single-molecule magnet and shows hysteretic magnetization characteristics with typical temperature and sweep-rate dependencies below a blocking temperature of about 4.4 K. The hysteresis loops collapse at zero field owing to fast quantum tunneling of the magnetization (QTM). The structural and electronic properties of cobalt(II) cubane 4 a, deposited on a highly oriented pyrolytic graphite (HOPG) surface, were investigated by means of STM and current imaging tunneling spectroscopy (CITS) at RT and standard atmospheric pressure. In CITS measurements the rather large contrast found at the expected locations of the metal centers of the molecules indicated the presence of a strongly localized LUMO. PMID- 20306504 TI - Highly stereoselective preparation of tertiary homoallylic alcohols with multiple stereogenic centers. PMID- 20306505 TI - Bioorthogonal turn-on probes for imaging small molecules inside living cells. AB - Glowing tags: a series of activatable ("turn-on") tetrazine-conjugated fluorescent probes was developed, which react rapidly in an inverse-electron demand [4+2] cycloaddition with strained dienophiles such as trans-cyclooctene, thereby strongly increasing the fluorescence intensity. The novel turn-on probes were applied for intracellular live-cell imaging of a microtubuli-binding trans cyclooctene modified taxol. PMID- 20306506 TI - Nanoparticle clusters light up in SERS. AB - Seeing double: nanoparticle clusters (dimers, trimers, etc.) have long been pursued as enhancers in surface-enhanced Raman spectroscopy research. A recent report presents an elegant approach for the high-yielding fabrication of dimers of silver nanospheres from nanocubes by controlled chemical etching. These nanoparticle dimers are capable of strongly enhancing Raman signals of surface adsorbates. PMID- 20306507 TI - Asymmetric dumbbells from selective deposition of metals on seeded semiconductor nanorods. AB - Sowing the seeds: the growth of Au and Ag(2)S nanoparticles at distinct positions on CdSe-seeded CdS heterostructured nanorods can be precisely controlled by variations in the concentration of the Au and Ag precursors, respectively. The ability to direct growth on the nanorods can lead to "Janus-type" structures where Au is located at the more reactive end of the nanorod, whilst Ag(2)S is located at the other (see picture; CdSe dark blue, CdS light blue, Au yellow, Ag(2)S gray). PMID- 20306508 TI - Synthesis of fluorene and indenofluorene compounds: tandem palladium-catalyzed suzuki cross-coupling and cyclization. AB - "Fluor" it: palladium-catalyzed tandem reactions, in which C(sp(3))-H bond activation is the key step (see scheme; DMA=dimethylacetamide), lead to substituted fluorenes and indenofluorenes through annulation in high yield and in one step. This method has potential for the preparation of other cyclic compounds, as well as substituted oligofluorenes and polyfluorenes. PMID- 20306509 TI - In-situ scanning transmission X-ray microscopy of catalytic solids and related nanomaterials. AB - The present status of in-situ scanning transmission X-ray microscopy (STXM) is reviewed, with an emphasis on the abilities of the STXM technique in comparison with electron microscopy. The experimental aspects and interpretation of X-ray absorption spectroscopy (XAS) are briefly introduced and the experimental boundary conditions that determine the potential applications for in-situ XAS and in-situ STXM studies are discussed. Nanoscale chemical imaging of catalysts under working conditions is outlined using cobalt and iron Fischer-Tropsch catalysts as showcases. In the discussion, we critically compare STXM-XAS and STEM-EELS (scanning transmission electron microscopy-electron energy loss spectroscopy) measurements and indicate some future directions of in-situ nanoscale imaging of catalytic solids and related nanomaterials. PMID- 20306510 TI - Experimental and theoretical study of a gold(I) aminonitrene complex in the gas phase. PMID- 20306511 TI - The association between effort-reward imbalance and coronary atherosclerosis in a Chinese sample. AB - BACKGROUND: Previous studies of job strain and coronary heart disease (CHD) have produced mixed findings. We aimed to examine the association between job stress evaluated by the effort-reward imbalance (ERI) model and coronary atherosclerosis assessed by coronary angiography in a Chinese sample. METHODS: Three-hundred twenty participants accepting coronary angiography for the first time were enrolled in series. Job stressors were evaluated by the ERI model. The presence and severity of CHD were assessed by measuring the coronary artery stenosis (the presence of >50% luminal stenosis in one or more major coronary arteries). The association between job stressors and CHD was examined by multivariate analysis. RESULTS: Compared with the low-level group, high-level effort, overcommitment, and ERI increased CHD risk with odds ratio (OR) 2.5 (95% confidence interval (CI): 1.2-5.0), 2.5 (95% CI: 1.2-5.0), 2.4 (95% CI: 1.2-4.9), respectively, after adjustment for confounders. They were also significantly positively correlated with the complexity of coronary artery lesions, respectively. Dose-response relationships were observed. CONCLUSIONS: ERI was associated with coronary artery lesions in a sample of Chinese workers. Longitudinal research and interventional designs are needed to confirm the mechanism and to provide evidence for the prevention of CHD. PMID- 20306512 TI - From stem cell to erythroblast: regulation of red cell production at multiple levels by multiple hormones. AB - This article reviews the regulation of production of red blood cells at several levels: (1) the ability of erythropoietin and adhesion to a fibronectin matrix to stimulate the rapid production of red cells by inducing terminal proliferation and differentiation of committed erythroid CFU-E progenitors; (2) the regulated expansion of the pool of earlier BFU-E erythroid progenitors by glucocorticoids and other factors that occurs during chronic anemia or inflammation; and (3) the expansion of thehematopoietic cell pool to produce more progenitors of all hematopoietic lineages. PMID- 20306513 TI - Enzymology of the carnitine biosynthesis pathway. AB - The water-soluble zwitterion carnitine is an essential metabolite in eukaryotes required for fatty acid oxidation as it functions as a carrier during transfer of activated acyl and acetyl groups across intracellular membranes. Most eukaryotes are able to synthesize carnitine endogenously, besides their capacity to take up carnitine from the diet or extracellular medium through plasma membrane transporters. This review discusses the current knowledge on carnitine homeostasis with special emphasis on the enzymology of the four steps of the carnitine biosynthesis pathway. PMID- 20306514 TI - Determination of antituberculosis drug concentration in human plasma by MALDI TOF/TOF. AB - Therapeutic drug monitoring allows to determine the best dosage regimen adapted to each patient optimizing the therapeutic benefits, while minimizing the risk for side effects. Here, the first methodological approach based on matrix assisted laser desorption/ionization source equipped with tandem time-of-flight (MALDI-TOF/TOF) mass spectrometry for the determination of the antituberculosis (anti-TB) drugs ethambutol, pyrazinamide, rifampicin, and streptomycin concentration in the plasma of tuberculosis-infected patients is reported. The volume of the plasma sample was 200 microL. Plasma samples were cleaned-up by protein precipitation and evaporated in a water bath under a nitrogen stream. The extracted samples were reconstituted with 200 microL of 50% methanol-0.03% formic acid solution (v/v), spiked with known amounts of anti-TB drugs, mixed (1:1) with a saturated matrix solution (4-hydroxybenzoic acid in 50% acetonitrile-0.1% trifluoracetic acid solution; v/v), and spotted onto the MALDI-TOF/TOF sample target plate. The anti-TB drug concentration was determined by standard additions analysis. Regression of standard additions was linear over the whole anti-TB drug concentration range explored (the final anti-TB drug concentration ranged from 0.20 to 200 pmol/microL). The absolute recovery of the anti-TB drugs ranged between 87 and 110%. The minimal ethambutol, pyrazinamide, rifampicin, and streptomycin concentration detectable by MALDI-TOF/TOF is 0.08, 0.20, 0.12, and 0.15 pmol/microL, respectively. PMID- 20306515 TI - Aminoacyl-tRNA synthetase-interacting multifunctional proteins (AIMPs): a triad for cellular homeostasis. AB - Aminoacyl-tRNA synthetases (ARSs) are highly conserved for efficient and precise translation of genetic codes. In higher eukaryotic systems, several different ARSs including glutamyl-prolyl-, isoelucyl-, leucyl-, methionyl-, glutaminyl-, lysyl-, arginyl-, and aspartyl-tRNA synthetase form a macromolecular protein complex with three nonenzymatic cofactors (AIMP1/p43, AIMP2/p38, and AIMP3/p18). Although the structure and functional implications for this complex formation are not completely understood, rapidly accumulating evidences suggest that this complex would work as a molecular hub linked to the multiple signaling pathways that involve the components of enzymes and cofactors. In this article, the roles of three nonenzymatic components of the multi-tRNA synthetase complex in the assembly of the components and in cell regulation are addressed. PMID- 20306516 TI - Relative acidities and structure analysis of cis and trans isomers of 1,5 oxazaspiro[5.5] undecane derivatives by multinuclear magnetic resonance. AB - The relative acidities of the cis and trans isomers of a series of 1,5 oxazaspiro[5.5]undecane derivatives were determined by measuring DeltapK in acid base titrations followed by (1)H NMR. Relative structural stabilities were determined by measuring substituent chemical shift and gamma-gauche effects in (13)C, (15)N, and (17)O NMR. Crystallographic characterization of a model spiro[5.5]undecane is presented to support the basicity in solid state. PMID- 20306517 TI - A theoretical NMR study of ortho and para-substituted benzenes compared with silabenzenes, pyridines and phosphabenzenes. AB - Calculations of absolute shieldings and nuclear-independent chemical shift [NICS(1)] values of 84 compounds (benzenes, silabenzenes, pyridines and phosphabenzenes) allowed to discuss the absolute shieldings in the function of Brown sigma(p)(+) substituent constant and to predict 71 new chemical shifts. The NICS(1) analysis of the aromaticity leads to the unexpected result for the silabenzenes that it is almost insensitive to substituent effects. In these set of compounds, it can be concluded that the aromaticity and its sensitivity to substituent effects are orthogonal. PMID- 20306518 TI - "Boost" of proton therapy helps reduce prostate cancer recurrence. PMID- 20306519 TI - CancerScope:Ohio educational program goes national. PMID- 20306520 TI - Hutchinson to build first US cancer clinic and training facility in Africa. PMID- 20306521 TI - Unnecessary breast cancer biopsies still performed. PMID- 20306522 TI - Gas phase isomeric differentiation of oleanolic and ursolic acids associated with heptakis-(2,6-di-O-methyl)-beta-cyclodextrin by electrospray ionization Fourier transform ion cyclotron resonance mass spectrometry. AB - Oleanolic acid (OA) and ursolic acid (UA) are isomeric triterpenoid compounds with similar pharmaceutical properties. Usually, modern chromatographic and electrophoretic methods are widely utilized to differentiate these two compounds. Compared with mass spectrometric (MS) methods, these modern separation methods are both time- and sample-consuming. Herein, we present a new method for structural differentiation of OA and UA by Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS) with the association of heptakis-(2,6-di O-methyl)-beta-cyclodextrin (DM-beta-CD). Exact MS and tandem MS (MS/MS) data showed that there is no perceptible difference between OA and UA, as well as their beta-cyclodextrin and gamma-cyclodextrin complexes. However, there is a remarkable difference in MS/MS spectra of DM-beta-CD complexes of OA and UA. The peak corresponding to the neutral loss of a formic acid and a water molecule could only be observed in the MS/MS spectrum of the complex of DM-beta-CD : OA. Molecular modeling calculations were also employed to further investigate the structural differences of DM-beta-CD : OA and DM-beta-CD : UA complexes. Therefore, by employing DM-beta-CD as a reference reagent, OA and UA could be differentiated with purely MS method. PMID- 20306523 TI - Strategies for developing design spaces for viral clearance by anion exchange chromatography during monoclonal antibody production. AB - The quality-by-design (QbD) regulatory initiative promotes the development of process design spaces describing the multidimensional effects and interactions of process variables on critical quality attributes of therapeutic products. However, because of the complex nature of production processes, strategies must be devised to provide for design space development with reasonable allocation of resources while maintaining highly dependable results. Here, we discuss strategies for the determination of design spaces for viral clearance by anion exchange chromatography (AEX) during purification of monoclonal antibodies. We developed a risk assessment for AEX using a formalized method and applying previous knowledge of the effects of certain variables and the mechanism of action for virus removal by this process. We then use design-of-experiments (DOE) concepts to perform a highly fractionated factorial experiment and show that varying many process parameters simultaneously over wide ranges does not affect the ability of the AEX process to remove endogenous retrovirus-like particles from CHO-cell derived feedstocks. Finally, we performed a full factorial design and observed that a high degree of viral clearance was obtained for three different model viruses when the most significant process parameters were varied over ranges relevant to typical manufacturing processes. These experiments indicate the robust nature of viral clearance by the AEX process as well as the design space where removal of viral impurities and contaminants can be assured. In addition, the concepts and methodology presented here provides a general approach for the development of design spaces to assure that quality of biotherapeutic products is maintained. PMID- 20306524 TI - Rural telepsychology services for children and adolescents. AB - Because of the overwhelming maldistribution of mental health specialists in metropolitan areas and the many underserved families living in rural settings, rural areas are natural homes for the use of telemedicine or videoconferencing technology for clinical services. The authors describe telepsychology services for rural clients, placing best psychology practices within the context of broader telemental health services. The goal is to approximate evidence-based child psychotherapy from face-to-face practice using the videoconferencing technology. Telepsychology is illustrated with a case report of a rural Hispanic teen and her family presenting through the teen's primary care clinic. PMID- 20306525 TI - Manual control of the upper esophageal sphincter. AB - OBJECTIVES/HYPOTHESIS: Oropharyngeal dysphagia (OPD) is common and costly. In order to improve quality of life for patients and costs to society, better treatments than currently available are needed. The author hypothesized that manual control of the upper esophageal sphincter (UES) is possible by pulling the larynx directly forward with anterior traction on the cricoid cartilage. The purpose of this investigation was to evaluate the effectiveness of manual control of the UES as a possible therapy for OPD. STUDY DESIGN: Retrospective chart review, medical device development, prospective cadaver trial, and prospective animal experiment. METHODS: Charts were reviewed of all persons with OPD who had a traction suture placed by the author around the anterior rim of the cricoid cartilage. The opening of the UES was assessed with and without traction on the suture. The ability of the cricoid suture to improve UES opening was evaluated under fluoroscopy. The Swallow Expansion Device (SED) was designed to manually control the UES. The ability of the SED to manually open the UES was evaluated. The SED was implanted in 10 cadavers, and 5,000 pulls of the device were performed on each specimen to evaluate for gross damage to the cricoid cartilage. The ability of the SED to open the UES was evaluated under direct laryngoscopy. The safety and efficacy of the SED was evaluated in an ovine model of OPD. The SED was implanted in eight sheep. Five thousand pulls of the device were performed on each animal weekly for 8 weeks. At the end of the study, damage to the cricoid cartilage was evaluated histologically, and the ability of the SED to open the UES and eliminate aspiration was assessed fluoroscopically. RESULTS: Six patients with OPD who had a suture placed around the anterior aspect of the cricoid cartilage were identified. Anterior traction on the suture improved UES opening by 0.36 cm (+/-0.19 cm) (P < .01). A titanium-coated ferrous implant that secures to the cricoid cartilage was fabricated (SED). An external magnetic device that affixes to the implant across intact skin was developed. Anterior traction of the SED opened the UES in cadavers a mean of 1.16 cm (+/-0.22 cm) (P < .001). Anterior traction on the SED opened the UES in sheep a mean of 1.27 cm (+/-0.36) (P < .001). Aspiration was eliminated in 100% of the animals. The implant became infected and had to be removed in one (12.5%) animal. Remodeling of the cricoid cartilage was evident, but there was no histologic evidence of cartilage damage. CONCLUSIONS: Manual control of the upper esophageal sphincter is possible. Simple anterior traction on the suture placed around the cricoid cartilage improved UES opening by 0.36 cm (+/-0.19) in a cohort of dysphagic patients. The Swallow Expansion Device opened the UES of cadavers and living sheep to superphysiologic proportions (P < .001). There was no histologic evidence of cricoid damage from prolonged use of the implant. PMID- 20306526 TI - Prevention of polyurethane oxidative degradation with phenolic antioxidants covalently attached to the hard segments: structure-function relationships. AB - Oxidative degradation of the polyurethane elastomeric (PU) components greatly reduces the efficacy of PU-containing cardiovascular devices. Covalently appending the phenol-based antioxidant, 4-substituted 2,6-di-tert-butylphenol (DBP), to PU hard segments effectively reduced oxidative degradation of the PU in vivo and in vitro in prior studies by our group. In these experiments, we analyze the contribution of the tethering molecule to the antioxidant capabilities of the DBP-modified PU. Bromoalkylation chemistry was used to link DBP to the hard segment of the polyether PU, Tecothane, via our original linker (PU-DBP) or variants containing side chains with one (PU-C-DBP) or three (PU-3C-DBP) carbons. Two additional DBP variants were fabricated in which the DBP group was appended to the alkyl chain via an oxygen atom (PU-O-DBP) or an amide linkage in the middle of the tether (PU-NHCO-DBP). All DBP variant films and unmodified control films were subject to oxidative degradation via 15-day immersion in a solution of 20% H(2)O(2) + 0.1M CoCl(2). At the end of the oxidation protocol, films were analyzed for the presence of oxidation-related endpoints via scanning electron microscopy, contact angle measurements, and Fourier transformation infrared spectroscopy (FTIR). All DBP-containing variants resisted oxidation damage significantly better than the unmodified control PU. SEM analysis of oxidized PU C-DBP and PU-O-DBP showed evidence of surface cracking, consistent with oxidative degradation of the PU surfaces. Similarly, there was a trend in increased ether crosslinking, a marker for oxidative degradation, in PU-C-DBP and PU-NHCO-DBP films. Consistent with these FTIR results, both PU-C-DBP and PU-NHCO-DBP had significant reductions in measured surface hydrophobicity as a result of oxidation. These data show for the first time that the choice of linker molecule significantly affects the efficiency of the linked phenolic antioxidant. PMID- 20306527 TI - Surgical management of primary retroperitoneal sarcoma. AB - BACKGROUND: Local recurrence after surgical resection is the main cause of disease-related mortality in patients with primary retroperitoneal sarcoma (RPS). This study analysed predictors of local recurrence and disease-specific survival. METHODS: A prospective database was reviewed to identify patients who underwent surgery for primary RPS between 1990 and 2009. Patient demographics, operative outcomes and tumour variables were correlated with local recurrence and disease specific survival. Multivariable analysis was performed to evaluate predictors for local recurrence and disease-free survival. RESULTS: Macroscopic clearance was achieved in 170 of 200 patients. The median weight of tumours was 4.0 kg and median maximum diameter 27 cm. Resection of adjacent organs was required in 126 patients. The postoperative mortality rate was 3.0 per cent. Seventy-five patients developed local recurrence during follow-up. At 5 years the local recurrence-free survival rate was 54.6 per cent and the disease-specific survival rate 68.6 per cent. Inability to obtain macroscopic clearance at resection and high-grade tumours were significant predictors for local recurrence and disease specific survival. CONCLUSION: Complete macroscopic excision should be the goal of surgical resection. Ability to resect a RPS completely and tumour grade are the most important predictors of local recurrence and overall survival. PMID- 20306528 TI - Identifying co-morbidity in surgical patients using administrative data with the Royal College of Surgeons Charlson Score. AB - BACKGROUND: Surgical outcomes are influenced by co-morbidity. The Royal College of Surgeons (RCS) Co-morbidity Consensus Group was convened to improve existing instruments that identify co-morbidity in International Classification of Diseases tenth revision administrative data. METHODS: The RCS Charlson Score was developed using a coding philosophy that enhances international transferability and avoids misclassifying complications as co-morbidity. The score was validated in English Hospital Episode Statistics data for abdominal aortic aneurysm (AAA) repair, aortic valve replacement, total hip replacement and transurethral prostate resection. RESULTS: With exception of AAA, patients with co-morbidity were older and more likely to be admitted as an emergency than those without. All patients with co-morbidity stayed longer in hospital, required more augmented care, and had higher in-hospital and 1-year mortality rates. Multivariable prognostic models incorporating the RCS Charlson Score had better discriminatory power than those that relied only on age, sex, admission method (elective or emergency) and number of emergency admissions in the preceding year. CONCLUSION: The RCS Charlson Score identifies co-morbidity in surgical patients in England at least as well as existing instruments. Given its explicit coding philosophy, it may be used as a co-morbidity scoring instrument for international comparisons. PMID- 20306529 TI - Response to induction therapy in oesophageal and cardia carcinoma using Mandard tumour regression grade or size of residual foci. AB - BACKGROUND: Tumour regression grade (TRG) is used to evaluate responses to induction therapy in cancer of the oesophagus or cardia. This study aimed to determine whether inclusion of node category could improve the prognostic accuracy provided by TRG, and explore the prognostic value of an alternative classification based on size of residual foci and node category. METHODS: Patients with oesophageal or cardia cancer treated with neoadjuvant chemoradiotherapy followed by resection were studied. Treatment-induced response at the primary site was evaluated by TRG and by a method whereby patients were classified as having no residual cancer, minimal residual disease (MRD) or as non responders. RESULTS: Between 2000 and 2007, 108 patients underwent resection. Disease-related survival decreased with increasing TRG in node-negative (N0) patients (P < 0.001), whereas in node-positive (N+) patients it was poor irrespective of TRG (P = 0.241). For N0 disease, 3-year survival in patients with MRD (58 (95 per cent confidence interval 26 to 80) per cent) was intermediate between that in patients with no residual cancer (85 (70 to 93) per cent) and non responders (28 (4 to 59) per cent). Worst prognosis was for N+ disease (21 (9 to 36) per cent). CONCLUSION: Node category should be considered when evaluating response to induction therapy in oesophageal or cardia cancer. A new classification based on size of residual foci and node category seems promising. PMID- 20306530 TI - Randomized clinical trial of different bandage regimens after foam sclerotherapy for varicose veins. AB - BACKGROUND: This trial compared outcomes after foam sclerotherapy in patients wearing compression bandaging for 24 h or 5 days after treatment. METHODS: Consecutive patients with primary uncomplicated varicose veins were randomized after foam sclerotherapy treatment. The primary endpoint was 6-week Aberdeen Varicose Vein Severity Score (AVVSS) and Burford pain score. RESULTS: Some 124 legs were randomized, 61 to 24 h and 63 to 5 days of bandaging. Target vein occlusion rates at 6-week duplex imaging were 90 and 89 per cent respectively (P = 0.842). There was no significant difference in phlebitis after 2 weeks (P = 0.445) or skin discoloration after 6 weeks (46 versus 40 per cent; P = 0.546). There was no significant difference in the change in AVVSS from baseline to 2 weeks (-0.29 versus -0.80; P = 0.717) or to 6 weeks (-5.89 versus -5.14; 95 per cent confidence interval (c.i.) for the difference -3.29 to 1.80; P = 0.563), or in change in Burford pain score from baseline to 2 weeks (-9.04 versus -2.80; P = 0.248) or to 6 weeks (-17.32 versus -8.46; 95 per cent c.i. for the difference 19.06 to 1.33; P = 0.088), or in change in Short Form 36 score from baseline to 6 weeks (2.02 versus 1.74; P = 0.903). CONCLUSION: There was no advantage to compression bandaging for more than 24 h when thromboembolus deterrent stockings were worn for the remainder of 14 days. REGISTRATION NUMBER: NCT00991497 (http://www.clinicaltrials.gov). PMID- 20306531 TI - Obesity and gastrointestinal cancer. AB - BACKGROUND: There is emerging evidence of a strong association between obesity and gastrointestinal cancer. This review summarizes the evidence from an epidemiological and pathophysiological perspective. METHODS: Relevant medical literature was identified from searches of PubMed and references cited in appropriate articles were identified. Selection of articles was based on peer review, journal and relevance. RESULTS: Numerous epidemiological studies consistently identified an increased risk of developing oesophageal adenocarcinoma and colorectal carcinoma in the obese. The association between obesity and other gastrointestinal malignancies was less robust. Sex seems important with respect to cancer risk. Adipose tissue, particularly viscerally located fat, is metabolically active and exerts systemic endocrine effects. Putative pathophysiological mechanisms linking obesity and carcinogenesis include the insulin-like growth factor axis, adipocytokines and sex steroids. CONCLUSION: A better understanding of the mechanisms that link obesity and cancer may uncover targets for intervention. Tackling obesity may result in a reduction in the incidence in addition to mortality of certain cancers in future. PMID- 20306532 TI - Introduction of laparoscopic colorectal cancer surgery in developing nations. PMID- 20306533 TI - Sulfate reduction at pH 4.0 for treatment of process and wastewaters. AB - Acidic industrial process and wastewaters often contain high sulfate and metal concentrations and their direct biological treatment is thus far not possible as biological processes at pH < 5 have been neglected. Sulfate-reducing bacteria convert sulfate to sulfide that can subsequently be used to recover metals as metal-sulfides precipitate. This study reports on high-rate sulfate reduction with a mixed microbial community at pH 4.0 and 4.5 with hydrogen and/or formate as electron donors. The maximum sulfate reducing activity at pH 4.0 was sustained for over 40 days with a specific activity 500-fold greater than previously reported values: 151 mmol sulfate reduced/L reactor liquid per day with a maximum specific activity of 84 mmol sulfate per gram of volatile suspended solids per day. The biomass yield gradually decreased from 38 to 0.4 g volatile suspended solids per kilogram of sulfate when decreasing the reactor pH from pH 6 to 4. The microorganisms had a high maintenance requirement probably due maintaining pH homeostasis and the toxicity of sulfide at low pH. The microbial community diversity in the pH 4.0 membrane bioreactor decreased over time, while the diversity of the sulfate reducing community increased. Thus, a specialized microbial community containing a lower proportion of microorganisms capable of activity at pH 4 developed in the reactor compared with those present at the start of the experiment. The 16S rRNA genes identified from the pH 4.0 grown mixed culture were most similar to those of Desulfovibrio species and Desulfosporosinus sp. M1. PMID- 20306534 TI - Factors in infancy and childhood related to reduced lung function in asthmatic children: a birth cohort study (BAMSE). AB - Changes in lung function due to childhood asthma have been reported to occur before school age, and to persist throughout life. The aim was to assess the relationship between aspects of lung function and asthma over time in 4,089 children participating in the large population-based birth cohort BAMSE. Questionnaires were administered at 1, 2, 4, and 8 years of age. At 4 and 8 years, children were invited to a clinical examination, in which 2,965 and 2,630 children participated, respectively. The examinations included blood sampling for evaluation of sensitization to airway allergens (n = 2,053), peak expiratory flow (PEF) measurements at 4 and 8 years (n = 1,957), and forced expiratory flows (n = 2,455) at 8 years. Asthma onset before the age of 4 years, but no thereafter, was at 8 years associated with impaired spirometric flows. This was seen irrespective of symptom presence after the age of 4. Reduced PEF growth between the age of 4 and 8 was seen only for the group of children with early onset transient asthma, while an association between sensitization and lung function was only seen in the late-onset asthma group. In conclusion, school children with asthma have reductions of spirometric flows when categorized as persistent or transient early onset asthma, even if this latter group of children is completely symptom-free at school age. PMID- 20306535 TI - Garlic as an inhibitor of Pseudomonas aeruginosa quorum sensing in cystic fibrosis--a pilot randomized controlled trial. AB - Pseudomonas aeruginosa forms biofilms in the cystic fibrosis lung. Quorum sensing (QS) controls biofilm maturation, immune evasion, antibiotic tolerance and virulence factor production. Garlic shows QS inhibitory activity in vitro and in animal models. We report the first clinical trial in man of a QS inhibitor.We randomized 34 patients to garlic or olive oil capsules (both 656 mg daily). Clinical outcomes and safety bloods were measured at baseline and after 8 weeks treatment. In this exploratory study, analysis was per protocol.Eight patients withdrew, leaving 26 for analysis (13 garlic). With placebo, there was a greater decline in mean (SD) percentage change from baseline FEV(1) [-3.6% (11.3)] than with garlic [-2.0% (12.3)]. This was not significant (mean difference = 1.6, 95% CI -12.7 to 15.9, P = 0.8). The mean (SD) increase in weight was greater with garlic [1.0% (2.0)] than with placebo [0.6% (2.0)]--non-significant (mean difference = 0.4%, 95% CI -1.3 to 2.0, P = 0.6). The median (range) change in clinical score with garlic was -1 (-3 to 5) and 1 (-1 to 4) with placebo (negative score means improvement). This was non-significant [median difference = -1 (-3 to 0), P = 0.16]. In the garlic group, seven patients had IV antibiotics versus five placebo. There was a highly significant correlation between plasma and sputum measurements of the QS molecule 3-oxo-C12-HSL (Pearson correlation coefficient = 0.914, P = 0.004). At the end of treatment five patients in each group had abnormal liver function or triglycerides and five garlic patients (one placebo) reported minor adverse effects.Garlic capsules were well tolerated. Although there was no significant effect of garlic compared to placebo in this pilot study, there was a suggestion of improvement with garlic which should be investigated in a larger trial. PMID- 20306536 TI - Bioluminescent imaging of reporter gene expression in the lungs of wildtype and model mice following the administration of PEG-stabilized DNA nanoparticles. AB - DNA nanoparticles (DNPs) formed by compacting DNA with polyethyleneglycolylated poly-L-lysine are a nonviral vector shown to be safe and efficacious in animals and humans. To extend our capabilities of assessing the efficacy and duration of expression achieved by DNPs, we tested the utility of bioluminescent imaging (BLI) of transgene expression in wildtype and cystic fibrosis (CF) mouse models. We tested the effect of route of administration, mouse coat color, anesthesia, dose, and promoter sequence on the level and duration of expression. Furthermore, we investigated the correlation between imaging and direct analysis of luciferase expression in lung homogenates. We found that intratracheal instillation, and the use of deep and prolonged anesthesia with avertin produced significantly higher expression compared with intranasal administration, and the use of lighter anesthesia with isoflurane. Although similar expression was observed for both dark and light coat animals, imaging signal intensity was attenuated in mice with dark fur. Furthermore, good correlation between imaging and direct homogenate analysis was observed for single dose (r = 0.96), and dose response studies in wildtype (r = 0.82) and CF mice (r = 0.87). Finally, we used imaging to track gene expression over a 56-day time course. We found that the human ubiquitin B promoter gives stable transgene expression up to 49 days following nanoparticle administration, while expression with the cytomegalovirus promoter diminished after 2 days and returned to background levels by day 14. Taken together, our results demonstrate that BLI is an effective and useful modality for measuring gene expression conferred by DNPs in the lung. PMID- 20306537 TI - Respiratory impedance and response to salbutamol in asthmatic Vietnamese children. AB - There is a high incidence of pediatric asthma in Vietnam, but little lung function data are available. The aim of the study was to compare respiratory resistance (Rrs), reactance (Xrs), and responses to salbutamol between asthmatic and healthy primary school children in Hanoi. Because respiratory mechanics vary along the breathing cycle, measurements were assessed separately in inspiration (Rrsi, Xrsi) and expiration (Rrse, Xrse).Inpatients with doctor-diagnosed asthma were measured 2-3 days following admission using the forced oscillation technique (FOT) at a single frequency (8 Hz). Z-scores and responses to salbutamol were compared between 102 asthmatics and 98 controls, and accuracy of group classification by FOT parameters was assessed by Youden index, an indicator to the proportion of subjects correctly classified in each group.In asthmatics versus controls, Rrsi-but not Rrse-was significantly larger and both Xrsi and Xrse were significantly more negative (P < 0.01). Both Rrs and Xrs responses to salbutamol were significantly larger in asthmatics than controls (P < 0.001). Youden indexes indicated response to salbutamol generally had better diagnostic values than Z-scores and was best discriminative first with Rrsi, then with Xrse.It is concluded that different FOT characteristics may be described in asthmatic and healthy Vietnamese children. The diagnostic value of each parameter depends upon the breathing cycle. Most useful in practice probably is the response to salbutamol measured by Rrsi. PMID- 20306538 TI - Olive oil during pregnancy is associated with reduced wheezing during the first year of life of the offspring. AB - OBJECTIVE: To test the hypothesis that consuming Mediterranean diet and using olive oil for cooking/dressing salads during pregnancy might be associated with less wheezing during the first year of the offspring's life. METHODS: A study was conducted in 1,409 infants (mean age, 16.6 +/- 2.5 months) attending healthy infant clinics in Spain. Dietary data of mothers' intake during pregnancy was collected by means of a parental food frequency questionnaire. Demographic information and data on wheezing during the first year of the offspring's life were also recorded. Infants were stratified according to any wheezing (42.2%) during the first year of life. RESULTS: In the univariate analysis, adherence to a Mediterranean diet and using olive oil for cooking/dressing salads during pregnancy were both significantly associated with less wheezing during the first year of life. However, after multivariate analysis, only olive oil consumption during pregnancy remained associated with less wheezing in the studied period (aOR = 0.57 [95% CI = 0.4-0.9]); whereas male gender (1.8 [1.4-2.3]), day care attendance (2.15 [1.5-3.1]), maternal asthma (2.16 [1.3-3.6]), maternal smoking during pregnancy (1.83 [1.3-2.2]), infant eczema (1.95 [1.3-2.9]), and mould stains on the household walls (1.72 [1.2-2.5]) remained associated with wheezing. CONCLUSION: Our findings suggest a protective effect (primary prevention) of olive oil use during pregnancy on wheezing during the first year of the offspring's life. PMID- 20306539 TI - Calibration issues for nanoindentation experiments: direct atomic force microscopy measurements and indirect methods. AB - This article discusses calibration issues for shallow depth nanoindentation experiments with Berkovich tips with respect to the accurate measurement of the diamond area function (DAF). For this purpose, two different calibration procedures are compared: (i) the direct measurement of the DAF through atomic force microscopy (AFM) imaging of the Berkovich tip at shallow depth and (ii) a novel indirect calibration method based on an iterative robust and converging scheme in which both reduced modulus and indentation hardness are simultaneously used. These results are obtained by indentation measurements on a standard specimen of fused silica, performed in the 0.5-200 mN load range with a Berkovich indenter. Direct tip shape measurements were carried out through different AFM methods. Comparisons with the standard indirect calibration procedure are also reported. For both the indirect calibration procedures a sensitivity and convergence study is presented. PMID- 20306540 TI - Antifibrillizing agents catalyze the formation of unstable intermediate aggregates of beta-amyloid. AB - Although Alzheimer's disease (AD) is characterized by the extracellular deposition of fibrillar aggregates of beta-amyloid (Abeta), transient oligomeric species of Abeta are increasingly implicated in the pathogenesis of AD. Natively unfolded monomeric Abeta can misfold and progressively assemble into fibrillar aggregates, following a well-established "on pathway" seeded-nucleation mechanism. Here, we show that three simple saccharides, mannose, sucrose, and raffinose, alter Abeta aggregation kinetics and morphology. The saccharides inhibit formation of Abeta fibrils but promote formation of various oligomeric aggregate species through different "off pathway" aggregation mechanisms at 37 degrees C but not at 60 degrees C. The various oligomeric Abeta aggregates formed when coincubated with the different saccharides are morphologically distinct but all are toxic toward SH-SY5Y human neuroblastoma cells, increasing the level of toxicity and greatly prolonging toxicity compared with Abeta alone. As a wide variety of anti-Abeta aggregation strategies are being actively pursued as potential therapeutics for AD, these studies suggest that care must be taken to ensure that the therapeutic agents also block toxic oligomeric Abeta assembly as well as inhibit fibril formation. PMID- 20306541 TI - Transcriptomic responses to sodium chloride-induced osmotic stress: a study of industrial fed-batch CHO cell cultures. AB - The rapidly expanding market for monoclonal antibody and Fc-fusion-protein therapeutics has increased interest in improving the productivity of mammalian cell lines, both to alleviate capacity limitations and control the cost of goods. In this study, we evaluated the responses of an industrial CHO cell line producing an Fc-fusion-protein to hyperosmotic stress, a well-known productivity enhancer, and compared them with our previous studies of murine hybridomas (Shen and Sharfstein, Biotechnol Bioeng. 2006;93:132-145). In batch culture studies, cells showed substantially increased specific productivity in response to increased osmolarity as well as significant metabolic changes. However, the final titer showed no substantial increase due to the decrease in viable cell density. In fed batch cultures, hyperosmolarity slightly repressed the cellular growth rate, but no significant change in productivity or final titer was detected. To understand the transcriptional responses to increased osmolarity and relate changes in gene expression to increased productivity and repressed growth, proprietary CHO microarrays were used to monitor the transcription profile changes in response to osmotic stress. A set of osmotically regulated genes was generated and classified by extracting their annotations and functionalities from online databases. The gene list was compared with results previously obtained from similar studies of murine-hybridoma cells. The overall transcriptomic responses of the two cell lines were rather different, although many functional groups were commonly perturbed between them. Building on this study, we anticipate that further analysis will establish connections between productivity and the expression of specific gene(s), thus allowing rational engineering of mammalian cells for higher recombinant-protein productivity. PMID- 20306542 TI - Tissue-engineered cartilage of porcine and human origin as in vitro test system in arthritis research. AB - The increasing prevalence of cartilage destruction during arthritis has entailed an intensified amount for in vitro cartilage models to analyze pathophysiological processes and to screen for antirheumatic drugs. Tissue engineering offers the opportunity to establish highly organized 3D cell cultures facilitating the formation of in vitro models that reflect the human situation. We report the comparison of porcine chondrocyte pellet and alginate bead cultures as model systems for human cartilage and the further development into a human system that was applied in an arthritis model. In porcine pellet and alginate cultures, formation of cartilage matrix similar to human matrix was verified by histology and PCR. As alginate beads could be cultivated batch-wise in one well of a multiwell plate, we further developed this setting into a human system. In contrast, each pellet had to be cultivated individually in one well of a multiwell plate, which is time consuming. Following stimulation of human chondrocyte alginate cultures with conditioned media from human synovial fibroblasts derived from arthritis patients, microarray analysis verified the induction of genes related to cartilage destruction (like MMP10, -12) and inflammation (like IL6, -8 and chemokines). Several genes are coding for proteins that are members of inflammatory and catabolic pathways. Belonging to the most affected pathways, we identified the focal adhesion, cytokine-cytokine receptor interaction, ECM-receptor signalling, Jak-STAT signalling, and toll-like receptor signalling pathways, all relevant in arthritis. Therefore, we demonstrate that engineered cartilage of porcine and human origin represents a powerful in vitro model for cartilage in vivo. PMID- 20306543 TI - Imatinib dose escalation in 74 failure or suboptimal response chronic myeloid leukaemia patients at 3-year follow-up. PMID- 20306544 TI - Kaplan-Meier method is inappropriate for estimating cumulative incidence of graft versus-host disease in the presence of competing events. PMID- 20306545 TI - Half metallic properties of LaSrVMoO6. AB - The recent synthesized LaSrVMoO(6) was speculated to be compensated half metal, i.e., half metal with zero magnetic moment. Based on the experimental structure, our first principles study indicates that it is ferrimagnetic and half metallic with the magnetic moment 2.0 microB when the electron correlation of Mo 4d electrons is larger than 2.72 eV. This indicates the strong electron correlation effect of Mo 4d electrons. Nonetheless, the obtained large magnetic moment (2.0 microB) contradicts with the experimental observed nearly zero magnetic moment. Although the large antisite defects of the experimental sample might be the reason to reduce the saturated magnetic moment, further physical insights need to be investigated. The spin-orbit coupling effect has minor effect on the studied properties. PMID- 20306546 TI - A flexible class of models for data arising from a 'thorough QT/QTc study'. AB - The standard methods for analyzing data arising from a 'thorough QT/QTc study' are based on multivariate normal models with common variance structure for both drug and placebo. Such modeling assumptions may be violated and when the sample sizes are small, the statistical inference can be sensitive to such stringent assumptions. This article proposes a flexible class of parametric models to address the above-mentioned limitations of the currently used models. A Bayesian methodology is used for data analysis and models are compared using the deviance information criteria. Superior performance of the proposed models over the current models is illustrated through a real dataset obtained from a GlaxoSmithKline (GSK) conducted 'thorough QT/QTc study'. PMID- 20306547 TI - A case study evaluation of ethics review systems for multicentre clinical trials. PMID- 20306548 TI - A case study evaluation of ethics review systems for multicentre clinical trials. PMID- 20306549 TI - Winds of change: growing demands for transparency in the relationship between doctors and the pharmaceutical industry. PMID- 20306550 TI - Making cars and making health care: a critical review. PMID- 20306551 TI - Towards more consistent use of generic quality-of-life instruments. PMID- 20306552 TI - Images. When pancreas and aorta mix-critical limb ischaemia, abdominal mass, and aortic compression. PMID- 20306555 TI - Significantly diminished long-term specificity of the BED capture enzyme immunoassay among patients with HIV-1 with very low CD4 counts and those on antiretroviral therapy. AB - OBJECTIVE: To estimate the proportion who test as recent infections by the BED capture enzyme immunoassay (BED) among patients about to commence, and those receiving, antiretroviral therapy. DESIGN: Cryopreserved plasma samples from HIV patients on the national antiretroviral treatment (ART) rollout program at Tygerberg Hospital HIV clinic, South Africa, were tested using the BED assay. PARTICIPANTS: Five hundred five patients qualifying for ART were included in this study. METHOD: All plasma samples from each patient were tested by BED. Basic demographic data, HIV-1 viral load, and CD4 count results were obtained from the laboratory database. MAIN OUTCOME: The proportion presenting as false recently infected is reported. RESULTS: Among patients, with presumed long-term HIV-1 infections, about to commence ART, 11.2% [95% confidence interval (CI): 8.3 to 14.5%] tested recent by BED. The proportion was higher among patients with CD4 counts < 50 cells per microliter [odds ratio 2.63, 95% CI: 1.39 to 5.00] and log10 HIV-1 viral load less than 4 [odds ratio 3.03, 95% CI: 1.05 to 9.09]. Proportions testing false recent increased from 11.2% before ART to 17%, 25%, 38%, and 56% at 0.5, 1, 1.5, and 2 years, respectively, after ART initiation. CONCLUSIONS: If the BED method is to be used for the accurate estimation of HIV incidence from cross-sectional surveys, it will be essential, before other statistical adjustment methods, to identify, at least, all cases who are on ART and all those with CD4 counts < 50 cells per microliter. The more general remaining problem is the unequivocal identification of all persons with long-term HIV infections. PMID- 20306556 TI - Abstracts of the 30th European Workshop for Rheumatology Research, 4-7 March 2010, Bamberg, Germany. PMID- 20306554 TI - Long-term efficacy and safety of the HIV integrase inhibitor raltegravir in patients with limited treatment options in a Phase II study. AB - BACKGROUND: Raltegravir in combination therapy has demonstrated potent suppression of HIV-1 with a favorable safety profile. This report provides 96 week efficacy and safety data from Protocol 005, a Phase II study. METHODS: HIV infected patients with very limited treatment options and failing antiretroviral therapy were randomized to raltegravir 200, 400, or 600 mg or placebo b.i.d., plus optimized background therapy for >or=24 weeks; all patients were then offered open-label raltegravir 400 mg b.i.d. Efficacy measurements included changes in viral load and CD4 count from baseline and percent of patients with HIV-1 RNA <400 and <50 copies/mL. RESULTS: One hundred and thirty-three patients received raltegravir and 45 received placebo. No dose-dependent differentiation in the safety or antiviral activity of raltegravir was observed during the double blind phase. For the combined raltegravir groups, mean change in viral load from baseline was -1.60 log10 copies/mL at week 48 and -1.38 log10 copies/mL at week 96 (observed failure approach). At week 48, HIV-1 RNA levels were <400 copies/mL in 68% of raltegravir recipients and <50 copies/mL in 55%; these levels were maintained in 55% and 48% of raltegravir recipients, respectively, at week 96 (noncompleter = failure). There were few discontinuations of raltegravir (4%) due to adverse events. CONCLUSIONS: In patients with limited treatment options, raltegravir with OBT had a potent and sustained antiretroviral effect and was generally well tolerated through 96 weeks. PMID- 20306557 TI - Leaning on advice. PMID- 20306558 TI - The missing climate change policy. AB - Affluent western individuals are increasingly fretting about the carbon dioxide emissions from their lifestyle and energy use but one key issue, having fewer children, is little considered. Nigel Williams reports. PMID- 20306559 TI - Stuart Pimm. PMID- 20306560 TI - Movies for use in public health training: a pilot method for movie selection and initial results. PMID- 20306561 TI - International accreditation process at a Latin American medical school: a 10 year experience. PMID- 20306562 TI - A temporary tattoo to simulate inflicted skin injury from child abuse. PMID- 20306563 TI - Teaching of gross anatomy for students of medicine by mind map-based power point slides. PMID- 20306564 TI - Intimate partner violence (IPV). Editor's introduction. PMID- 20306565 TI - Can persons with dementia be engaged with stimuli? AB - OBJECTIVES: To determine which stimuli are 1) most engaging 2) most often refused by nursing home residents with dementia, and 3) most appropriate for persons who are more difficult to engage with stimuli. METHODS: Participants were 193 residents of seven Maryland nursing homes. All participants had a diagnosis of dementia. Stimulus engagement was assessed by the Observational Measure of Engagement. RESULTS: The most engaging stimuli were one-on-one socializing with a research assistant, a real baby, personalized stimuli based on the person's self identity, a lifelike doll, a respite video, and envelopes to stamp. Refusal of stimuli was higher among those with higher levels of cognitive function and related to the stimulus' social appropriateness. Women showed more attention and had more positive attitudes for live social stimuli, simulated social stimuli, and artistic tasks than did men. Persons with comparatively higher levels of cognitive functioning were more likely to be engaged in manipulative and work tasks, whereas those with low levels of cognitive functioning spent relatively more time responding to social stimuli. The most effective stimuli did not differ for those most likely to be engaged and those least likely to be engaged. CONCLUSION: Nursing homes should consider both having engagement stimuli readily available to residents with dementia, and implementing a socialization schedule so that residents receive one-on-one interaction. Understanding the relationship among type of stimulus, cognitive function, and acceptance, attention, and attitude toward the stimuli can enable caregivers to maximize the desired benefit for persons with dementia. PMID- 20306566 TI - Reliability and validity of an algorithm for the diagnosis of normal cognition, mild cognitive impairment, and dementia: implications for multicenter research studies. AB - BACKGROUND: The traditional consensus diagnosis (ConsDx) of normal cognition, mild cognitive impairment (MCI), and dementia relies on the reconciliation of an informant-based report of cognitive and functional impairment by a physician diagnosis (PhyDx), and a neuropsychological diagnosis (NPDx). As this procedure may be labor intensive and influenced by the philosophy and biases of a clinician, the diagnostic algorithm (AlgDx) was developed to identify individuals as cognitively normal, with MCI, or dementia. METHODS: The AlgDx combines the PhyDx with the NPDx, using a diagnostic algorithm that provides cognitive diagnoses, as defined by the National Alzheimer Coordinating Center/Uniform Data Set nomenclature. Reliability of the AlgDx was assessed in 532 community-dwelling elderly subjects by its concordance with the ConsDx and association with two biomarkers, medial temporal atrophy (MTA) scores of brain magnetic resonance imaging scans, and Apolipoprotein E (ApoE)-epsilon4 genotype. RESULTS: A high degree of concordance was observed between ConsDx and AlgDx with a weighted Cohen's kappa of 0.84. Concordance of the AlgDx to the same ConsDx categories ranged from 85% to 92%. Excellent discriminative validity was observed using AlgDx, MTA scores, and ApoE-epsilon4 allele frequencies, each of which distinguished subjects with amnestic MCI and dementia from normal subjects. CONCLUSION: The AlgDx of normal cognition, MCI, and dementia is a valid alternative that reduces time, effort, and biases associated with the ConsDx. The inherent reliability of a fixed algorithm, together with its efficiency and avoidance of individual bias, suggests the AlgDx may be used in longitudinal, multisite clinical trials, and population studies of MCI and dementia. PMID- 20306567 TI - Synergistic antifibrotic effect of verapamil and interferon-gamma in rats: partially based on enhanced verapamil oral bioavailability. AB - OBJECTIVE: The objective of this study was to investigate the synergistic antifibrotic effect of verapamil and interferon-gamma (IFN-gamma) on rat liver fibrosis and its potential pharmacokinetic-based mechanism. METHODS: Rat liver fibrosis model was successfully established, and both the therapeutic effects and pharmacokinetic parameters of verapamil were evaluated after the administration of verapamil with or without IFN-gamma. The activities of cytochrome P450 3A (CYP3A) and the expression of multidrug resistance (Mdr) mRNA were measured in liver and small intestine. RESULTS: The results showed the synergistic antifibrotic effect of verapamil and IFN-gamma in rat liver fibrosis, in terms of decreased serum L-alanine aminotransferase activity and liver hydroxyproline content and improved liver histopathology, when compared with rats treated with verapamil or IFN-gamma alone. Meanwhile, the area under the curve of verapamil increased significantly after single administration of verapamil and IFN-gamma and the concentration of verapamil in plasma increased, but the metabolite : parent ratio of verapamil decreased after consecutive administrations of verapamil and IFN-gamma. Furthermore, the activities of CYP3A in both the liver and the small intestine and the expression of Mdr in small intestine decreased in rats treated with verapamil and IFN-gamma. CONCLUSION: All these results indicated that the combination of verapamil and IFN-gamma exerts a synergistic antifibrotic effect on rat liver fibrosis. The mechanism was partially based on the enhanced oral bioavailability of verapamil by increasing the intestinal absorption as well as reducing the first-pass metabolism, through inhibition of CYP3A activity and P-glycoprotein expression by IFN-gamma PMID- 20306568 TI - Subfulminant hepatitis B during treatment with adalimumab in a patient with rheumatoid arthritis and chronic hepatitis B. AB - We report a case of reactivation of hepatitis B virus (HBV) infection with subacute liver failure during administration of adalimumab, followed by a literature review of all 19 published cases, with a focus on the effect of antiviral prophylaxis. Eight patients were given prophylaxis and had a good outcome. Of the 11 patients without prophylaxis, six patients developed a reactivation and needed to stop anti-TNFalpha therapy (P = 0.017). One patient developed an acute liver failure, necessitating urgent liver transplantation. One patient died. Administration of anti-TNFalpha therapy can lead to HBV reactivation, with a possible lethal outcome. High-risk patients and possibly all patients should be screened for hepatitis B surface antigen and anti-HBV core antibody before starting anti-TNFalpha therapy. Administration of antiviral prophylaxis proves beneficial in prevention of reactivation in hepatitis B surface antigen positive patients. PMID- 20306569 TI - Premedication with oral midazolam with or without parental presence. AB - BACKGROUND AND OBJECTIVE: In this study, we aimed to investigate whether the combination of low-dose (0.25 mg kg(-1)) midazolam premedication with parental presence can effectively reduce anxiety at induction as well as provide a smoother emergence. METHODS: Institutional ethics committee approval and informed consent from one of the parents were obtained prior to the study. Sixty ASA grade I or II children undergoing surgery were enrolled in the study. Children were randomized to receive either 0.5 mg kg(-1) midazolam orally (group M) or 0.25 mg kg(-1) midazolam orally with parental presence (group MP) or parental presence alone (group P). The child's anxiety and sedation scores were evaluated as 1-4 points on the Anxiety Scale and as 0-4 points on the University of Michigan Sedation Scale (UMSS), respectively, at the entrance to the operating room and for tolerance to the face mask. Heart rate, the mean arterial blood pressure and O2 saturation (%) were assessed at repeated intervals before and after induction. At the end of surgery, the child's Anxiety Scale score, UMSS score, Observer's Pain Scale (OPS) score and FLACC score were also assessed. RESULTS: There were no differences between groups in demographic variables and duration of surgery or anaesthesia. Mean blood pressure changes were similar between groups at measured intervals, but the heart rate was higher in group M before and after induction of anaesthesia (P<0.05). UMSS score was greater in both midazolam groups (groups M and MP) in the preoperative period (P<0.05). Anxiety Scale scores for anxiolysis were higher in groups M and MP than in group P (less anxious and more sedated) at 20 min after premedication, at the entrance to the operating room and at mask tolerance time points (P<0.05). During recovery there was no significant difference in sedation, recovery scores or behavioural anxiety assessment between groups, Anxiety Scale score, UMSS score, FLACC score, Visual Analog Scale (VAS) score and Observer's Pain Scale score in groups MP, M and P. CONCLUSION: Preoperative administration of midazolam 0.5 mg kg(-1) for premedication alone, without parental presence at induction, and that of low-dose midazolam 0.25 mg kg(-1) for premedication with parental presence at induction are both equally effective in reducing separation anxiety and providing a smooth emergence. However, parental presence alone, without midazolam for premedication, is not an adequate approach for this outcome. If the environment for parental presence is convenient, the dose of midazolam may be reduced and induction and emergence conditions may still be of high quality. PMID- 20306570 TI - Lateral Intracanalicular growth of vestibular schwannomas and surgical planning. AB - OBJECTIVE: To assess the lateral growth pattern in adult patients with growing sporadic vestibular schwannomas (VSs) and to decide if repeat imaging is always necessary immediately preoperatively when determining the route of access for microsurgical excision. PATIENTS: Adults identified as having VS growth from serial scanning (3 scans per patient) between 1994 and 2007 in a single referral center. Neurofibromatosis Type 2 patients and those with tumor growth already to the fundus of the internal auditory canal were excluded. INTERVENTION: Retrospective review of serial imaging. MAIN OUTCOME MEASURES: Lateral growth (in millimeters) in the internal auditory canal. RESULTS: Thirty subjects were identified who had continued serial imaging after documented growth, of whom 26 (87%)showed no lateral growth and 4 (13%) showed growth of 1 mm.This was determined over a median time period of 26 months(interquartile range, 20Y36.5 mo). The time frame between the second and third scans looked at the period of continued observation in this group of subjects in whom known previous tumor growth had occurred, which was 13 months (interquartile range, 9.25Y16.75 mo), and this is the most reliable time frame upon which a practice-changing decision regarding repeat scanning can be made from these data. CONCLUSION: Sporadic VSs that are documented to be growing on serial imaging do not seem to grow to any significant degree in a lateral direction within the internal auditory canal.The results imply that scans performed within a year of any surgical intervention need not be repeated to assess concerns of any further lateral growth while accepting that repeat imaging may be required for other clinical reasons. Key Words:Internal auditory canal PMID- 20306571 TI - Prevalence of vitamin D deficiency among immigrants to South Dakota. AB - INTRODUCTION: Vitamin D deficiency is gaining increased attention nationally. Recent clinical cases suggest that this condition is a significant problem in local refugee populations. The Sioux Falls Health Department recently implemented a policy of screening and treating all new refugees as part of the new refugee examinations at Falls Community Health Center. METHODS: Data from this screening during the first nine months of 2009 were reviewed and analyzed for prevalence of hypovitaminosis D in this population. Results from a total of 157 individuals were included in this study. RESULTS: Two percent of this population had initial calcidiol levels below the detection threshold. Six percent were severely deficient, defined as <15 ng/mL, and 58 percent were mildly deficient (15-32 ng/mL). Only 36 percent had levels above 32 ng/mL, considered adequate for bone health, with a mere 1 percent showing optimal levels of > 50 ng/mL. CONCLUSIONS: Hypovitaminosis D represents a significant public health issue among recent immigrants in Minnehaha County, S.D., and warrants aggressive attention by both primary care and public health professionals. PMID- 20306572 TI - Quality focus: physicians remain the foundation of health improvement. PMID- 20306573 TI - NY: failure to follow-up with timely CT scans: RN fails to notify pt. of need for follow-up scans. PMID- 20306574 TI - CA: np testified as to welts in child abuse case: abusive mother lost custody of children. PMID- 20306575 TI - Flawed logic. PMID- 20306576 TI - Purification and characterization of a barley aleurone abscisic acid-binding protein. PMID- 20306577 TI - Ransom for rainforests. PMID- 20306578 TI - New biofuel questions. PMID- 20306579 TI - Butterfly effect. PMID- 20306580 TI - [A decent proposal]. PMID- 20306581 TI - [Prevention and diagnosis of HIV in infants]. PMID- 20306582 TI - [Editorial comment on: Health and quality of life in urology: issues in general urology and urological oncology]. PMID- 20306583 TI - [Editorial comment on: Outcomes of maximal androgen blockade in prostate cancer patients at a health area with type 2 reference hospital. Part 2. Quality of life: application of EORTC QLQ-PR25 instrument and global results. Quality-of life adjusted survival. Pharmaceutical expenses and cost-utility]. PMID- 20306584 TI - [Editorial comment on: SolidFlex--the fourth generation in endoscopy]. PMID- 20306586 TI - Hand amputation at sea: comment re: successful hand replantation in a seafarer after long-distance helicopter evacuation. A case report. PMID- 20306585 TI - Some thoughts on the history of race and health in the United States of America. PMID- 20306587 TI - A medical mission to Swaziland, part 2. PMID- 20306588 TI - Mahatma Gandhi and the Anglo-Boer War. PMID- 20306589 TI - Rhabdomyosarcoma metastatic paratesticular. AB - OBJECTIVES: To report one case of metastatic paratesticular rhabdomyosarcoma in a 14 years old patient, classified as stage IIb (IRSG). METHODS: After treatment with radical surgery (orchiectomy and lymphadenectomy), polychemotherapy and radiotherapy, showed good evolution initially. RESULTS: 12 months after surgery the patient is disease free. CONCLUSIONS: Adjuvant treatment is very important in the prognosis of this kind of tumors. PMID- 20306590 TI - X-raying human origins: Dragutin Gorjanovic-Kramberger and the first application of radiography in palaeoanthropology. PMID- 20306591 TI - Metastatic squamous cell carcinoma of the penis. PMID- 20306592 TI - A medical mission to Swaziland, part 3. PMID- 20306593 TI - [Prostatic-rectal fistula after trasurethral resection of the prostate]. PMID- 20306594 TI - Medicine and war -- Josep Trueta (1897-1977). PMID- 20306595 TI - Musician's maladies -- George Frideric Handel (1685-1759). PMID- 20306596 TI - Musicians' maladies -- the curse of the Mendelssohns. PMID- 20306597 TI - The introduction of Rontgen Rays and radiography into South Africa in 1896. PMID- 20306598 TI - Guest editors' introduction to the special section on Shape Analysis and Its Applications in Image Understanding. PMID- 20306599 TI - War and medicine -- Sir Edward "Weary" Dunlop (1907-1993). PMID- 20306600 TI - A pill problem: prescription drug abuse is the fastest growing form of substance abuse. PMID- 20306601 TI - Crime and treatment: overcrowded prisons and addicted inmates are a tough challenge for lawmakers. PMID- 20306602 TI - [Editorial comment on: Use of absorbable gelatin sponge as an adjunct to "totally tubeless percutaneous nephrolithotomy"]. PMID- 20306603 TI - The development of neuroscience through the centuries, part 1. PMID- 20306604 TI - Medicine and music: Borodin and Liszt: a medico-musical friendship. PMID- 20306605 TI - Giants and dwarfs in the Bible. PMID- 20306607 TI - The development of neuroscience through the centuries: part 2. PMID- 20306606 TI - Women in medicine: Virginia Apgar (1909-1974). PMID- 20306608 TI - [Screening of ADAMs that can mediate the generation of soluble MHC I]. AB - AIM: To screen ADAMs that can mediate the generation of soluble MHCI using HEK293 cells are study model. METHODS: ADAM8, ADAM10, ADAM15 or ADAM17 cDNA expressing vector s were separately constructed with pcDNA3. 1/V5 as vectors and were transfected into HEK293 cells. Hygromycin B was used to screen the cells that stably expressed ADAMs. After HEK293 cells were sell-surface labeled with biotin and cultured for another 4 h and soluble MHC I the was examined by SDS-PAGE, Western blot and enhanced chemiluminescence. RESULTS: HEK293 cells stably expressing ADAMs were successfully obtained and the over-expression of ADAM10 or ADAM17 increased the release of soluble MHC I. CONCLUSION: ADAM10 and ADAM17 have the potentials of mediating the generation of soluble MHC I. PMID- 20306609 TI - Introduction to fantastic anthropology. PMID- 20306610 TI - Women in medicine: Maude Abbott (1869-1940). PMID- 20306611 TI - Self-advocacy: an essential skill. PMID- 20306612 TI - Evidence-based advocacy: using Photovoice to identify barriers and facilitators to community participation after spinal cord injury. AB - People with spinal cord injury (SCI) face many environmental barriers to community participation. In this article, a community-based participatory research (CBPR) project that implemented the Photovoice method with 10 individuals with SCI to gather evidence of the environmental factors affecting their participation in the community in and around Charleston, SC, is described. The specific aim of this project was to use Photovoice to create an evidence base of environmental barriers and facilitators to community participation through analysis of data based on the World Health Organization's International Classification of Functioning, Disability and Health taxonomy of environmental factors. Barriers and facilitators were most frequently photographed in the built environment. The participants have started to share their evidence of issues affecting citizens with disabilities with the public and policy makers. The results of this project illustrate that Photovoice is effective in empowering individuals with SCI to address environmental factors affecting their community participation. PMID- 20306613 TI - Palliative or hospice care? Understanding the similarities and differences. AB - With advances in health care and medical technology, the focus of medical care has been on curing. As people live longer, the possibility of experiencing chronic and life-limiting disease not only increases but also spurs the ethical question "Is length of life or quality of life most important?" Palliative care may be confused with hospice care, as both focus on symptom management and improved quality of life for those with chronic life-limiting disease. A better understanding of each healthcare option is needed for appropriate and timely patient referral. The purpose of this article is to identify the similarities and differences between these two options, clarify when referral is appropriate for hospice or palliative care services, and discuss the nurse's role in caring for patients with chronic disease. PMID- 20306614 TI - Effects of a skin rehabilitation nursing program on skin status, depression, and burn-specific health in burn survivors. AB - The objective of this study was to identify the effects of a skin rehabilitation nursing program (SRNP) on skin status, depression, and burn-specific health in Korean burn survivors. A pretest-posttest design with a nonequivalent control group was used to examine the effects of SRNP for 3 months in a group of 26 burn survivors. The SRNP group of 13 burn survivors received massage therapy 30 minutes three times a week for 3 months compared to a control group of 13 burn survivors receiving typical care. The SRNP group showed no significant changes in the burn scar, subjective skin status, depression, or burn-specific health. Burn survivors receiving SRNP had reduced burn scar depth after the intervention compared to the control group. The findings of this study demonstrate that SRNP for burn survivors may improve burn scars, and findings suggest that future studies with a larger sample should be conducted using SRNP as an intervention for burn survivors. PMID- 20306615 TI - Incorporating bedside reporting into change-of-shift report. AB - Communication failures during shift reports are a leading cause of sentinel events in the United States. Providing adequate information during change-of shift reporting is essential to promoting patient safety. In addition, patients want to be more involved in decisions regarding their plan of care. The purpose of the article is to discuss how a stroke rehabilitation unit was able to implement bedside change-of-shift reporting to meet both of these goals. PMID- 20306616 TI - Rheumatoid arthritis: coping with disability. AB - This article explains the components of disability as related to rheumatoid arthritis (RA) using an expansion of Nagi's Model of Disability (Jette, 2006) and the World Health Organization's (WHO) International Classification of Functioning, Disability, and Health (ICF). In addition, suggestions for ways in which nurses can offer patients choices in physical functional therapy and psychosocial aspects of coping with the chronicity of RA are discussed. Understanding how RA relates to the holistic management of the patient will allow nurses to modify and suggest additional measures to enhance the outcomes of patient-centered care. Many degrees of disability exist that affect the physical and psychosocial domains of RA. Nurses should identify the primary issues influencing disability and assemble supporting resources or a multidisciplinary team to manage a person's disabilities. As nurses develop and maintain relationships with patients, they are able to follow through with the care plan continuum and recognize when modifications are needed. PMID- 20306617 TI - Efficacy of combined oral-intravesical oxybutynin hydrochloride treatment for patients with overactive detrusors and indwelling urethral catheters. AB - The purpose of this article is to investigate the efficacy of intravesical oxybutynin hydrochloride (OH) to treat patients with overactive detrusors who are unresponsive to oral anticholinergic therapy alone. Twenty-five patients who were treated with oral OH for overactive detrusor (but who did not respond to treatment and were using indwelling urethral catheters) were given intravesical OH without changing oral treatment. Pre- and posttreatment bladder capacities were compared in urodynamic studies. The study showed that positive clinical results can be achieved with combined oral and intravesical OH treatments in patients with overactive detrusors who had indwelling urethral catheters because of severely reduced bladder capacity. However, a significant number of patients discontinued this treatment because of infection and difficulty in performing the procedure. Clinicians and rehabilitation nurses should provide education and support to eliminate these problems. In addition, the development of single-use standard sterile OH preparations for intravesical applications may increase the efficacy of the method. PMID- 20306618 TI - Working smarter...not harder. PMID- 20306619 TI - The best of times or the worst of times. PMID- 20306620 TI - Severe falciparum malaria: a case report. PMID- 20306621 TI - Question: does beta-blocker therapy improve outcomes in patients with congestive heart failure with normal left ventricular function (diastolic dysfunction)? PMID- 20306622 TI - Developmental disorders of language and literacy: special issue. AB - Language and literacy are cognitive skills of exceptional complexity. It is therefore not surprising that they are at risk of impairment either during development or as a result of damage (e.g. stroke) later in life. Impaired language and literacy can arise from a general learning impairment. However, two developmental disorders, specific language impairment (SLI) and dyslexia, which affect oral and written language, respectively, are 'specific' in that they are not part of a more general learning difficulty. SLI and dyslexia each affect 5 10% of the general population, and they are the focus of the papers in this special issue. PMID- 20306623 TI - Towards a further characterization of phonological and literacy problems in Dutch speaking children with dyslexia. AB - This longitudinal study examined the development of phonology and literacy in Dutch-speaking children at family risk of dyslexia and in matched controls. Measures were administered in kindergarten (before the start of formal reading instruction), in first and in third grade. Children, diagnosed with dyslexia in third grade, showed impaired phonological awareness (PA), verbal short-term memory, and rapid automatic naming ability (RAN) at all time points, with the deficit in PA aggravating over time. These children also performed more poorly in letter knowledge, word and nonword reading accuracy and speed, and spelling at each time point. Children at family risk of dyslexia who did not fulfil criteria for dyslexia, scored more poorly than low-risk controls on the literacy and phonological measures that required the most fine-grained phonological representations. This suggests that the family risk of dyslexia is continuous rather than discrete. Hierarchical regression analyses demonstrated that PA and RAN were initially the most important instigators of reading accuracy and reading speed, respectively. After 2 years of reading instruction, only RAN predicted reading speed and accuracy. Letter knowledge, reading accuracy, and reading speed also contributed to the development of PA. PMID- 20306624 TI - Identifying specific language impairment in deaf children acquiring British Sign Language: implications for theory and practice. AB - This paper presents the first ever group study of specific language impairment (SLI) in users of sign language. A group of 50 children were referred to the study by teachers and speech and language therapists. Individuals who fitted pre determined criteria for SLI were then systematically assessed. Here, we describe in detail the performance of 13 signing deaf children aged 5-14 years on normed tests of British Sign Language (BSL) sentence comprehension, repetition of nonsense signs, expressive grammar and narrative skills, alongside tests of non verbal intelligence and fine motor control. Results show these children to have a significant language delay compared to their peers matched for age and language experience. This impaired development cannot be explained by poor exposure to BSL, or by lower general cognitive, social, or motor abilities. As is the case for SLI in spoken languages, we find heterogeneity within the group in terms of which aspects of language are affected and the severity of the impairment. We discuss the implications of the existence of language impairments in a sign language for theories of SLI and clinical practice. PMID- 20306625 TI - Gesture production and comprehension in children with specific language impairment. AB - Children with specific language impairment (SLI) have difficulties with spoken language. However, some recent research suggests that these impairments reflect underlying cognitive limitations. Studying gesture may inform us clinically and theoretically about the nature of the association between language and cognition. A total of 20 children with SLI and 19 typically developing (TD) peers were assessed on a novel measure of gesture production. Children were also assessed for sentence comprehension errors in a speech-gesture integration task. Children with SLI performed equally to peers on gesture production but performed less well when comprehending integrated speech and gesture. Error patterns revealed a significant group interaction: children with SLI made more gesture-based errors, whilst TD children made semantically based ones. Children with SLI accessed and produced lexically encoded gestures despite having impaired spoken vocabulary and this group also showed stronger associations between gesture and language than TD children. When SLI comprehension breaks down, gesture may be relied on over speech, whilst TD children have a preference for spoken cues. The findings suggest that for children with SLI, gesture scaffolds are still more related to language development than for TD peers who have out-grown earlier reliance on gestures. Future clinical implications may include standardized assessment of symbolic gesture and classroom based gesture support for clinical groups. PMID- 20306626 TI - Deductive reasoning in children with specific language impairment. AB - The diagnosis of specific language impairment (SLI) requires non-verbal ability to be in the normal range, but little is known regarding the extent to which general reasoning skills are preserved during development. A total of 122 children were tested; 40 SLI, 42 age-matched controls, and 40 younger language matched controls. Deductive reasoning tasks were given in both verbal and pictorial presentation types, namely the relational inference task and the reduced array selection task (RAST). Pictorial presentation facilitated all groups for all tasks equally. For the relational inference task, SLI performance was below both age and language matches. For the RAST, contextual information facilitated all groups equally. SLI performance was intermediate between age and language matches. It is concluded that the non-verbal versus verbal distinction is a complex one and that non-verbal reasoning can draw upon linguistic processes. It is also suggested that SLI reasoning depends upon precise task demands, here the need to sequence information in working memory, and the need for explicit reasoning with conditional rules. Reasoning processes may not be equivalent to normally developing children, even when tasks appear non-verbal. PMID- 20306627 TI - Phonological awareness and mathematical difficulty: a longitudinal perspective. AB - The present longitudinal study sought to investigate the impact of poor phonology on children's mathematical status. From a screening sample of 256 five-year-olds, 82 children were identified as either typically achieving (TA; N = 31), having comorbid poor phonology and mathematical difficulties (PDMD; N = 31), or having only poor phonology (phonological difficulty, PD; N = 20). Children were assessed on eight components of informal and formal mathematics achievement at ages 5-7 years. PD children were found to have significant impairments in some, mainly formal, components of mathematics by age 7 compared to TA children. Analysis also revealed that, by age 7, approximately half of the PD children met the criteria for PDMD, while the remainder exhibited less severe deficits in some components of formal mathematics. Children's mathematical performance at age 5, however, did not predict which PD children were more likely to become PDMD at age 7, nor did they differ in terms of phonological awareness at age 5. However, those PD children who later became PDMD had lower scores on verbal and non-verbal tests of general ability. PMID- 20306628 TI - Growth of reading skills in children with a history of specific language impairment: the role of autistic symptomatology and language-related abilities. AB - Individuals with a history of specific language impairment (SLI) often have subsequent problems with reading skills, but there have been some discrepant findings as to the developmental time course of these skills. This study investigates the developmental trajectories of reading skills over a 9-year time span (from 7 to 16 years of age) in a large sample of individuals with a history of SLI. Relationships among reading skills, autistic symptomatology, and language related abilities were also investigated. The results indicate that both reading accuracy and comprehension are deficient but that the development of these skills progresses in a consistently parallel fashion to what would be expected from a normative sample of same age peers. Language-related abilities were strongly associated with reading skills. Unlike individuals with SLI only, those with SLI and additional autistic symptomatology had adequate reading accuracy but did not differ from the individuals with SLI only in reading comprehension. They exhibited a significant gap between what they could read and what they could understand when reading. These findings provide strong evidence that individuals with SLI experience continued, long-term deficits in reading skills from childhood to adolescence. PMID- 20306629 TI - Do tasks make a difference? Accounting for heterogeneity of performance of children with reading difficulties on tasks of executive function: findings from a meta-analysis. AB - Research studies have implicated executive functions in reading difficulties (RD). But while some studies have found children with RD to be impaired on tasks of executive function other studies report unimpaired performance. A meta analysis was carried out to determine whether these discrepant findings can be accounted for by differences in the tasks of executive function that are utilized. A total of 48 studies comparing the performance on tasks of executive function of children with RD with their typically developing peers were included in the meta-analysis, yielding 180 effect sizes. An overall effect size of 0.57 (SE .03) was obtained, indicating that children with RD have impairments on tasks of executive function. However, effect sizes varied considerably suggesting that the impairment is not uniform. Moderator analysis revealed that task modality and IQ-achievement discrepancy definitions of RD influenced the magnitude of effect; however, the age and gender of participants and the nature of the RD did not have an influence. While the children's RD were associated with executive function impairments, variation in effect size is a product of the assessment task employed, underlying task demands, and definitional criteria. PMID- 20306630 TI - Non-word repetition in Dutch-speaking children with specific language impairment with and without reading problems. AB - Recently, English studies have shown a relationship between non-word repetition (NWR) and the presence of reading problems (RP). Children with specific language impairment (SLI) but without RP performed similarly to their typically developing (TD) peers, whereas children with SLI and RP performed significantly worse on an NWR task. The current study was undertaken to investigate whether this difference in NWR performance is also found in a language with a transparent orthography- Dutch. The study included 15 TD children and 29 children with SLI. All children performed an NWR task that included non-words of 2-5 syllables in length. Children with SLI - RP (N = 11) did not differ on any of the four conditions from the TD group, whereas the children with SLI + RP (N = 18) scored more poorly on the 3-, 4-, and 5-syllable items compared to the TD group. NWR performance was significantly poorer on the 3- and 4-syllable conditions for children with SLI + RP compared to SLI - RP. To conclude, NWR is specifically affected in children with SLI + RP who are learning to read and write in a transparent orthography. Our data underline the dependency relation between literacy development and NWR performance in children with SLI. PMID- 20306631 TI - Production and comprehension of pronouns by Greek children with specific language impairment. AB - This study contributes to the characterization of the deficit in specific language impairment (SLI) by investigating whether deficits in the production and comprehension of pronouns in Greek children with SLI are best accounted for by domain-general or domain-specific models of the language faculty. The Greek pronominal system distinguishes between acoustically salient and non-salient forms, which are both interpreted on semantic/thematic grounds, and non-salient forms (object clitics) interpreted on syntactic grounds either in spec-head agreement or syntactic dependencies incurring feature checking through movement/chain formation. The results revealed a significant effect of the syntactic configuration on the production and comprehension of object clitics. Children with SLI were significantly impaired in the production and comprehension of those clitics that enter into operations necessitated by complex syntactic dependencies involving feature checking through movement/chain formation. Thus, the data support the computational grammatical complexity hypothesis and indicate that the deficits associated with object clitics in Greek-speaking children with SLI result from domain-specific impairment with syntactic dependencies incurring feature checking at the clause level involving movement/chain formation. PMID- 20306632 TI - Interesting mix of articles reflecting ongoing research areas in leprosy. PMID- 20306633 TI - Leprosy global statistics: beware of traps. PMID- 20306634 TI - Enhanced global strategy for further reducing the disease burden due to leprosy: 2011-2015. PMID- 20306635 TI - Interventions for erythema nodosum leprosum. A Cochrane review. AB - INTRODUCTION: Treatment for erythema nodosum leprosum (ENL), an immunological complication of leprosy, is diverse. We undertook a systematic review as it was not clear which treatments were most beneficial. METHODS: We did a systematic search to identify randomised controlled trials (RCTs) comparing treatment with placebo, no treatment or another therapy. Two authors assessed quality and checked data. RESULTS: We included 13 studies involving 445 participants. These trials assessed: betamethasone, thalidomide, pentoxifylline, clofazimine, indomethacin and levamisole. The quality of the trials was generally poor and no results could be pooled due to the treatments being so heterogeneous. Treatment with thalidomide showed a significant benefit compared to aspirin (RR 2.43; 95% CI 1.28 to 4.59). Clofazimine treatment was superior to prednisolone (more treatment successes; RR 3.67; 95% CI 136 to 9.91) and thalidomide (fewer recurrences; RR 0.08; 95% CI 0.01, 0-56). Minor adverse events were significantly lower in participants on a low dose thalidomide regimen compared to a high dose thalidomide regimen (RR 0.46; 95% CI 0.23 to 0.93). Significantly more minor adverse events were reported in participants taking clofazimine compared with prednisolone (RR 1.92; 95% CI 1.10 to 3.35). None of the studies assessed quality of life or economic outcomes. CONCLUSION: There is some evidence of benefit for thalidomide and clofazimine, but generally we did not find clear benefits for interventions in the management of ENL. This does not mean they do not work because the studies were small and poorly reported. Larger studies using clear definitions and internationally recognised scales are urgently required. PMID- 20306636 TI - The role of radiology in nerve function impairment and its musculoskeletal complications in leprosy. AB - Conventional techniques, such as plain radiography and bone-scintigraphy, were used in the past to evaluate skeletal changes in patients with leprosy. More recent publications focus on radiological imaging of affected nerves, and involve advanced modalities such as Computed Tomography (CT-scan), Ultrasonography (US), and Magnetic Resonance Imaging (MRI). US and MRI can play an especially important role in the evaluation of nerve involvement in newly diagnosed patients, and also during leprosy reactions. This is important, because when nerve involvement is diagnosed in time, it may be reversible with adequate treatment. Radiological modalities can also play an important role during the followup of patients with leprosy with nerve function impairment. Skeletal and soft-tissue abnormalities occur, even after treatment. The so-called neuropathic foot is a well known consequence. Because of nerve function impairment, there is a constant risk of developing ulcers and subsequent osteomyelitis, or neuro-osteoarthropathy (Charcot foot or tarsal disintegration), which can lead to the amputation of the affected limb. Different radiological modalities can be used during the evaluation and follow-up of patients with leprosy with a neuropathic foot. With this up-to-date review, we highlight the importance and potential role of radiological imaging techniques in leprosy. PMID- 20306637 TI - Hypophosphorylation of NF-H and NF-M subunits of neurofilaments and the associated decrease in KSPXK kinase activity in the sciatic nerves of swiss white mice inoculated in the foot pad with mycobacterium leprae. AB - OBJECTIVE: To study the phosphorylation state of neurofilament (NF) proteins and activity of KSPXK kinase in the sciatic nerves of Swiss white (S/W) mice inoculated in the hind foot pads with M. leprae. DESIGN: Test group includes S/W mice inoculated in the foot pads with freshly harvested human derived (viable) M. leprae. Control groups were constituted by (1) Age matched un-inoculated mice, (2) Mice similarly inoculated with M. smegmatis and (3) heat killed M. leprae. Phosphorylation state of NF was studied using Western blot analysis and phosphor specific NF antibody (SMI 31; Sternberger Monoclonals, Inc.). The KSPXK kinase activity was assayed by using KSPXK fusion protein in a radiometric method using gamma(22)P ATP. RESULTS: Several fold increase in M. leprae numbers was seen in viable M. leprae group while M. smegmatis failed to show any fold increase in the foot pads of S/W mice. Western immunoblot analysis of cytoskeletal preparation from sciatic nerves of uninoculated mice and mice inoculated with M. smegmatis showed immunoreactivity to SMI 31 antibody and protein bands corresponding to both NF-H and NF-M at all the time points from 4-20 months post inoculation. In case of viable M. leprae; SMI 31 reactive protein bands were seen at 4 months but not at any of the later intervals, i.e., between 6-20 months. With heat killed M. leprae transient loss of immunoreactivity to SMI 31 was seen. Decrease in KSPXK kinase activity was recorded in sets inoculated with viable and heat killed M. leprae, and corroborated with loss of immunoreactivity seen in WBs reacted with SMI 31 antibody. CONCLUSIONS: Alterations in the sciatic nerve NF cytoskeleton was seen following inoculation in the hind foot pad with both viable and heat killed M. leprae. The hypophosphorylation of NF observed in this study corroborates with the earlier observations in human leprous nerves. PMID- 20306638 TI - Detection of serum antibodies to M. leprae major membrane protein-II in leprosy patients from Indonesia. AB - BACKGROUND: Sero-diagnostic methods are the easiest way of diagnosing an infectious disease in developing countries. In leprosy, phenolic glycolipid-1 (PGL-I) based methods for the detection of leprosy are currently available, but the use of these methods has been hindered due to the inherent problems of sensitivity. We previously showed that antibodies to Major Membrane Protein-II (MMP-II) derived from Mycobacterium leprae could be used to diagnose leprosy in Japan. METHODS: Sera from patients and healthy individuals were collected with informed consent and the anti-MMP-II antibody levels of the sera were measured by enzyme-linked immunosorbent assay. The study was conducted at South Sulawesi and Bali, in Indonesia. The study population included 40 each of multibacillary leprosy and paucibacillary leprosy patients, 30 tuberculosis and 16 patients with typhoid. RESULTS: We evaluated the anti-MMP-II antibody levels in Indonesian individuals. The cut-off value was determined from receiver operator characteristic curve as 0.124 using the O.D. titers for patients with multibacillary leprosy, so that the sensitivity of the test was 97.5% and the specificity taking healthy individuals as controls was 984%. Using the determined cut-off values, 98% of multibacillary (MB) leprosy and 48% of paucibacillary (PB) leprosy patients had positive levels of anti-MMP-II antibodies, 13% of patients with typhoid and 22% of the household contacts of MB leprosy had positive levels of anti-MMP-II antibodies. CONCLUSIONS: Our results suggest that measuring anti MMP-II antibody levels could facilitate the detection of leprosy in endemic countries. PMID- 20306640 TI - Healthcare seeking behaviour and delay in diagnosis of leprosy in a low endemic area of China. AB - Delay in diagnosis of leprosy can increase the risk of nerve function impairments and promote the transmission of the infection in a community. In order to understand the factors associated with the delays in diagnosis of leprosy, a questionnaire-based interview was conducted to collect information on the delays among 88 newly diagnosed leprosy patients. The results showed that delay was common and associated with the high rate of disability in the study population. The total mean delay was 50.18 months (median 36 months). The mean patient delay was 24-4 months (median 9.5 months) and the mean health service delay was 257 months (median 12 months). Patients with leprosy reported a variety of symptoms/signs at an early stage of the disease, particularly numbness and tingling. Ignorance of the illness was reported to be the main reason for the patient's delay. Health seeking actions ranged from 1 to 50 with a mean of 7.2 after becoming aware of the first symptom/sign. The effectiveness of early diagnosis of leprosy through health promotion in the population needs to be validated and continuous training on leprosy among healthcare providers is needed. PMID- 20306639 TI - Analysis of newly detected leprosy cases and misdiagnosis in Wuhan (1990-2004). AB - OBJECTIVE: To analyse the leprosy epidemiological trends and the diagnostic delay in newly detected cases between 1990 and 2004 in Wuhan. METHODS: We reviewed the clinical records of all 80 leprosy patients who were referred to the Wuhan Institute of Dermatology and Venerology (WHIDV) during 1990 and 2004, and the clinical information of diagnosis-delayed cases was analysed. RESULTS: Patients were determined as lepromatous leprosy (LL, 24, 30%), borderline lepromatous leprosy (BL, 15, 18-75%), borderline leprosy (BB, 9, 11.25%), borderline tuberculoid leprosy (BT, 12, 15%), and tuberculoid leprosy (TT, 20, 25%), respectively. The patients were more likely to present with multibacillary (MB, 48 cases) rather than with paucibacillary (PB, 32 cases). Among the 80 newly detected patients, 53 cases (66.25%) had been misdiagnosed (51 cases in general hospitals, two cases in WHIDV), 23 cases were treated with hospitalisation in department of dermatology of general hospitals. Up to 20 kinds of dermatological conditions involved in case misdiagnosis. CONCLUSIONS: Misdiagnosis of dermatological conditions and ignorance of the disease among general practitioners and hospital dermatologists were the main causes of diagnostic delay in Wuhan. which is leading to incorrect treatment for patients suffering with a variety of damage due to leprosy. PMID- 20306641 TI - Detection of Mycobacterium leprae DNA in nine-banded armadillos (Dasypus novemcinctus) from the Andean region of Colombia. AB - OBJECTIVE: To use DNA detection methodologies to test for M. leprae in nine banded armadillos inhabiting forested regions located around the cities and towns where leprosy patients have been identified. DESIGN: Ear lobe biopsies of 22 nine banded armadillos were studied during a 2 year period. The biopsies were processed for DNA extraction and amplification by nested polymerase chain reaction (N-PCR) of a fragment of the high copy DNA locus of M. leprae known as R LEP. RESULTS: Nine of the 22 (40.9%) armadillos evaluated showed positive signals for M. leprae. Sequencing confirmed that PCR products were identical to the corresponding region of M. leprae DNA. CONCLUSIONS: In Colombia, South America, the consumption of and contact with the nine-banded armadillo (Dasypus novemcinctus) are common, ignoring the fact that this animal can host and be a possible zoonotic reservoir of Mycobacterium leprae, the causal agent of leprosy. This is the first study demonstrating that M. leprae is present in nine-banded armadillos in a region of Colombia using specific DNA detection. The possibility of leprosy transmission due to contact and consumption of armadillo meat or use of blood for therapeutic purposes should be further investigated. PMID- 20306642 TI - The decline of leprosy in Japan: patterns and trends 1964-2008. AB - OBJECTIVE: Our purpose was to elucidate the patterns and trends of autochthonous leprosy in Japan from 1964 to 2008, to compare them with the findings from other studies of leprosy in decline, and to determine whether M. leprae transmission persists in Japan. DESIGN: Data on registered leprosy cases in Japan in the period 1964-2008 were analysed with reference to trends in case detection, geographical distribution, age at diagnosis, sex, classification, family history and broad correlation with socioeconomic conditions. RESULTS: A consistent decline in leprosy case detection was observed in all areas of the country over the period 1964-2008. Highest incidence was consistently in Okinawa, the southernmost part of Japan. Autochthonous leprosy has not been reported in anyone born in Japan since 1980. Increasing average age and a shift towards lower latitudes were demonstrated throughout the period. There was an inverse association between regional measures of wealth and leprosy incidence. CONCLUSIONS: Leprosy has declined throughout the past century in Japan. Autochthonous transmission has probably stopped in mainland Japan, but may still occur at a low level in Okinawa, the country's southernmost region. Analyses of data on autochthonous cases revealed patterns similar to those reported in other countries with declining leprosy. Detailed comparisons between countries with very low leprosy incidence may help us to better understand the epidemiology of leprosy. PMID- 20306643 TI - Case finding survey for leprosy in Iran: Bandar Abbas and Minab. PMID- 20306644 TI - Latapi's lepromatosis (Lucio's leprosy) without Lucio's phenomenon in a pubertal boy. PMID- 20306645 TI - Surgical treatment of bilateral paralytic lagophthalmos using scapha graft in a case of lepromatous leprosy. PMID- 20306646 TI - Comments on van Veen et al's simplified nerve function tests. PMID- 20306647 TI - [Reliability of the diagnoses of external post-mortem examinations in non-natural deaths before and after the German reunification]. AB - In Germany, the unsatisfactory quality of external post-mortem examinations and the low autopsy rate of only 5 % of all deaths are often criticized. Based on the autopsy protocols of 8,593 cases of non-natural death of the Leipzig Institute of Legal Medicine (1985 to 1989--practice in the former German Democratic Republic; 1990 to 1994 - time around the fall of the Berlin wall, and 2000 to 2004- practice in the Federal Republic of Germany) the diagnosis indicated in the death certificate was compared with that of the autopsy report. Beside a drastic decrease in the number of autopsies performed, it was found that in 72% of the cases the clinical and the autoptical cause of death corresponded completely, whereas in 9.2% there was only partial and in 15.4% no correspondence at all. The lack of correspondence increased from 13.8% (1985-1989) to 18.0% (2000-2004). The low rate of correspondence in the causes of domestic deaths was particularly alarming. There were obvious differences in quality among different groups of specialists in determining the cause of death. PMID- 20306648 TI - [Analysis of clinical forensic examination reports on sexually abused children]. AB - Clinical forensic examinations of children suspected of having been sexually abused are increasingly part of the routine of medicolegal institutes. The findings collected from 2005 until 2007 at the Institute of Legal Medicine of the Hanover Medical School were analysed retrospectively. Altogether, 91 children (74 females, 17 males, mean age 8.7 years) were examined. In 87.9% of the cases, the examination had been ordered by the police. In 73.6%, the victim knew the suspected perpetrator well or he was a family member. 40.7% of the children were seen within 72 hours after the alleged abuse. 12.1% of the children had extragenital lesions. In 27% of the victims, marked anogenital injuries were found, which were characteristic of sexual abuse in 9%. In 18 cases (20.2%), swabs were taken for spermatozoa detection. 3 of 17 vaginal smears showed positive test results for sperm up to 21 hours after the incident. No spermatozoa could be detected in 4 anal and 2 oral swabs as well as in one swab taken from the skin of the victim's thigh. In summary, the evaluation shows that early clinical forensic examination of children suspected of having been sexually abused is crucial to document evidence that is highly significant for the investigation and court proceedings. Often suspected sexual child abuse cannot be proved by medical findings alone. Of course, the absence of anogenital injuries does nor rule out sexual abuse. PMID- 20306649 TI - [Attempted and completed homicide in Hamburg--a comparison of two six-year periods]. AB - The present study compared cases of attempted and completed homicide in Hamburg from 1984 to 1989 and from 1995 to 2000 (n = 887). Data collection was performed using the police records. Attempted homicide showed a significant increase (34.8% vs. 57.9%, P < 0.0001). The majority of the victims and offenders were male with the share of male victims increasing from 59.7% to 74.2% (P < 0.0001). The age of the victims and offenders ranged between 22 and 40 years in both periods. The share of persons with a nationality other than German increased both in the victims (23.1% vs. 37.2%, P < 0.0001) and in the offenders (26.8% vs. 37.2%, P < 0.0001). The most common motives were interpersonal conflicts and robbery. The most frequently used forms of violence were sharp force, blunt force and strangulation. PMID- 20306650 TI - [Humidity as a necessary condition for latent fingerprint detection with ninhydrin--a practice-oriented and inexpensive method using potassium citrate]. AB - Ninhydrin is a common reagent for latent fingerprint detection on porous surfaces, and water in the form of humidity is an essential factor in the developing process. Beside climatic chambers running on electricity, the required humidity can also be reached by using saturated salt solution. The influence of different climatic conditions on the developing process is shown by using test strips (as analytical standards). For the developing process, a saturated solution of tripotassium citrate at room temperature proved to be particularly suitable. Tripotassium citrate is a non-hazardous compound, which is also used as a food additive without quantitative limitation, is environmentally safe and produced from renewable resources. In a closed box, a saturated tripotassium citrate solution generates a relative humidity of about 64% in a temperature range of 15 to 35 degrees C. PMID- 20306651 TI - [Unusual questions of evidence in a case of offensive post-mortem dismemberment]. AB - In cases of post-mortem dismemberment, the main medicolegal task apart from the identification and assignment of body parts to one or several individuals is the determination of the cause of death and the course of events. Notably in cases of offensive postmortem dismemberment, the medicolegal findings on the victim may be of special importance also for the psychiatric evaluation of the suspect. In a case of offensive post-mortem dismemberment, parts of the body were found in a stone quarry and in the apartment where the victim and the suspect had lived together. Since the suspect refused to make a statement, the medicolegal findings were of great relevance for the psychiatric evaluation. In the first trial, in which the psychiatric expert was not present when the forensic pathologist gave his opinion, the Regional Court acquitted the suspect of murder and committed him to a psychiatric hospital. The accused successfully appealed on points of law, as the form and content of the psychiatric expert opinion did not comply with the requirements of procedural law and the forensic psychiatric state of the art. In a second trial, additional psychiatric experts were summoned. In that hearing, the task of the medicolegal expert was to reconstruct the course of events as far as possible to create a reliable basis for the psychiatric evaluation, as the suspect refused to make a statement both with regard to his personal circumstances and the facts of the case and did not agree to a psychiatric exploration either. The motivational and morphological criteria of the medicolegal classification as offensive post-mortem dismemberment with a cannibalistic background are discussed. In addition, some issues to be answered such as the detection of bloodstains on nonporous surfaces by means of leucocrystalviolet and the time of heat exposure of burned body parts are dealt with. PMID- 20306652 TI - Interleukin-18 expression in rheumatoid artheritis synovial tissue and its relation to disease activity. AB - The study investigates the expression and function of interleukin-18 (IL-18) in synovial tissue (ST) of patients with rheumatoid arthritis (RA). IL-18 and IL-18 receptors (IL-18R) mRNA expression was detected by reverse transcription polymerase chain reaction (RT-PCR). Expression of IL-18 at protein level was analyzed by western blotting technique. Cytokines; (IL-18 and interferon-[IFN gamma]) in culture supernatants from ST cell organ and synovial cultures and IL 18 in sera and synovial fluid (SF) were measured by ELISA. The ST samples were taken from 44 RA patients and thirty osteoarthritis patients (OA) were included as controls. Using RT-PCR, for ST of RA and OA, mRNA expression of IL-18 was detected in 39 out of 44 (88.6%) RA patients and in 14 out of 30 (46.6%) OA controls. However, mRNA expression of IL-18 R alpha and beta chains were detected in 39 and 35 out of 44 (88.6% and 79.5%) RA patients, respectively. ST of OA did not express mRNA of alpha and beta chains of IL-18 R. In vitro study of IL-18 production by ST showed significantly higher levels in RA compared to that of OA patients (P<0.005). Western blotting revealed that the expression of ST IL-18 was more in RA than in OA (P < 0.02). Only IL-12, but not IL-18, stimulates IFN-gamma production by RAST cells [mean +/- SD = 246 +/- 15 pg/ml]. However, when IL-12 was combined with IL-18, they could significantly stimulate IFN-gamma production by RAST cells [M +/- SD = 629 +/- 18 pg/ml]. OA ST cells did not respond to either IL-12 alone or when combined to IL-18. II-18 was detected at significantly higher levels in sera and SF of RA patients in comparison to OA controls (p < 0.001 and p < 0.01, respectively). IL-18 level in the sera and SF in RA patients was significantly correlated with disease activity. In conclusion, IL-18 is expressed in RA synovia and contributes to the production of IFN-gamma by the infiltrating T-cells. These cytokines could play a proinflammatory role in the pathogenesis of RA. PMID- 20306653 TI - The preparation of A purified immunogenic pertactin from B. pertussis. AB - Pertactin, an outer membrane protein of Bordetella pertussis, was purified to apparent homogeneity. The purified pertactin was first extracted from the B. pertussis cells (strain 165) by heating for 1 h at 60 degrees C, followed by DEAE Sepharose and Affi-Gel Blue chromatography. The purified pertactin migrated as a single band of 69-kDa and a pl of 5.9 and retains a high immunogenicity. The rabbit anti- pertactin antisera shows high specificity in ELISA. The purified pertactin is a potential candidate as immunogen for preparation of diagnostic reagents and as a vaccine component. PMID- 20306654 TI - Role of IL-13 in the pathogenesis of bronchial asthma. AB - Asthma is a chronic inflammatory disease of the lung. Although it is multifactorial in origin, the inflammatory process is believed to be a result of inappropriate immune responses to common aeroallergens in genetically susceptible individuals. As such, it has been reported that Th2 cytokines play a pivotal role in the pathogenesis of disease. The aim of this study was to evaluate the role of IL-13 in the pathogenesis of bronchial asthma. The study was carried out on 71 subjects out of which 54 were asthmatic patients and 17 were normal controls. Patients with bronchial asthma were further classified according to the National Asthma Education and Prevention Program (NAEPP) into 4 groups: intermittent, mild persistent, moderate persistent and severe persistent. IL-13 serum levels were estimated in patients and controls by ELISA. Asthmatic patients showed a statistical significant elevation of serum IL-13 levels (mean = 78.5 +/- 64.5 pg/ml) as compared to controls (mean = 51.8 +/- 24.9 pg/ml). When patients with different degrees of severity were compared, a significant increase in serum IL 13 was found in patients with intermittent asthma (mean = 106 +/- 105 pg/ml) as compared to those with mild (mean = 63.6 +/- 14.7 pg/ml) and severe persistent asthma (mean = 64.9 +/- 29.1 pg/ml). Only patients with intermittent asthma showed a highly significant increase in serum IL-13 than controls. No statistically significant difference was found between patients not on steroids, patients on inhaled steroids and those on systemic steroids. A statistically significant increase in IL-13 serum levels was observed in patients not on steroids compared to normal controls. A significant increase in blood eosinophil counts was found in patients during acute asthmatic attacks as compared to those who were stable. In conclusion, IL-13 is a key cytokine with critical role in the immunopathogenesis of bronchial asthma. Steroids can downregulate IL-13, but inhaled steroids alone might not be able to abolish the airway remodeling process in asthmatics. Although patients with intermittent asthma are asymptomatic in between exacerbations, inflammation and remodeling are ongoing in their lungs. PMID- 20306655 TI - HER-2 gene amplification, serum nucleosomes, CEA and CA15.3 tumor markers in breast cancer patients. AB - Breast cancer is the most frequently diagnosed cancer in women in the world, for which tumor markers are needed for early detection, clinical prognistication and monitoring. The study was designed to assess the usefulness of HER-2 gene amplification, serum nucleosomes, CEA and CA15.3 tumor markers in the diagnosis of invasive ductal carcinoma and analyze whether their levels correlate with the clinicopathological features. The study was carried out on fifty patients with invasive ductal carcinoma and 25 age matched women with benign breast diseases (BBD). Cancer patients were categorised into three subgroups according to absence (-) or presence (+) of axillary lymph nodes (N) or presence of distant metastasis (M+) into: subgroup I (N-) included 15 patients, subgroup II (N+) included 20 patients and subgroup III (M+) included 15 patients. All individuals were subjected to CBC, fasting blood sugar, liver & kidney function tests, CEA and CA15.3 by electrochemiluminescence, serum nucleosomes by cell death detection ELISA and amplification of HER-2 gene by differential PCR. The HER-2 gene PCR results were + ve in 28% of cancer patients; 20% of subgroup I, 25% of subgroup II and 40% of subgroup III, but in none of the BBD patients. HER-2 gene amplification results showed significant positive correlation with tumor grade. Serum nucleosomes showed significant increase in cancer patients as compared to that of BBD group, significant negative correlation with HER-2 gene amplification and significant positive correlation with CA15.3. Serum nucleosomes was the most sensitive marker (76% versus 32% and 50% for CEA & CA15.3 respectively) but the least specific (72% versus 92% and 96% for CEA & CA15.3 respectively). Elevated CEA and CA15.3 levels were detected in 13.3% and 33.3% respectively in node negative patients, these percentage increased in node positive patients to 20% and 40% and in metastatic patients to 66.7% and 80% respectively. In conclusion, serum nucleosomes is more sensitive but less specific marker than CEA and CA15.3 for diagnosis of early-stage breast cancer. HER-2 gene amplification is a potential prognostic marker for advanced stage breast cancer. PMID- 20306656 TI - Vascular endothelial growth factor in preterm infants with respiratory distress syndrome. AB - Respiratory distress syndrome (RDS) secondary to surfactant deficiency is a common cause of morbidity and mortality in premature infants. An increasing evidence suggests that vascular endothelial growth factor (VEGF) may contribute to surfactant secretion and pulmonary maturation. This study determines cord blood VEGF levels in preterm infants and investigates its association with the development and severity of RDS. 50 preterm neonates and 10 healthy full term neonates were included in this study. All preterm neonates were subjected to full history taking, complete clinical examination, chest X-ray and laboratory investigations including arterial blood gases, CBC and C-reactive protein. Cord blood samples were obtained for determination of VEGF levels using ELISA. Cord blood VEGF level was significantly lower in preterm infants with RDS (7.76 +/- 2.28 in mild cases and 3.64 +/- 1.22 in severe cases) as compared to preterm infants without RDS (16.61 +/- 4.58) and controls (16.48 +/- 3.23) (p < 0.001). Infants with severe RDS especially those with small gestational age (GA), low birth weight (BW) and low APGAR score at 1 and 5 minutes had significantly lower cord blood VEGF level than those with mild RDS (p < 0.001). There was no significant effect on the level of VEGF regarding maternal use of antenatal steroids, premature rupture of membrane (PROM) and sex of newborn infants (P > 0.05). The sensitivity and specificity of cord blood VEGF test was 80% and 62% respectively with positive predictive value (PPV) of 80% and negative predictive value 56% at cutoff point of 10.02 ng/mL. It's concluded that cord blood VEGF elevation is associated with the absence of RDS, and that its level negatively correlates with the severity of the disease and duration on ventilation. PMID- 20306657 TI - Molecular detection of survivin expression, antiapoptotic gene, and other prognostic markers, how they are correlated and how it could be of prognostic value in chronic myeloid leukemia patient. AB - Chronic myeloid leukemia (CML) is a malignant disease of heampoitic stem cell resulting from clonal expansion of leukemic myeloid cells. Survivin is a recently identified member of the inhibitor of apoptosis protein family. The aim of the work is to analyze the expression of survivin in CML patient in chronic, accelerated and blastic phases and its correlation with other prognostic markers. The study included 50 CML patients (24 females and 26 males) and 10 healthy individuals (4 female and 6 male) as a control group. The studied groups were classified into group (I), 10 healthy individuals as a control group, group (II), 20 CML patients in chronic phase, Group (III), 15 CML patients in accelerated phase and Group (IV), 15 CML patients in blastic phase. The groups were subjected to clinical history and examination, CBC, ESR, BM aspiration (only patients), determination of serum survivin, IL-6 and beta2M levels by ELISA and survivin gene expression by quantitative real time PCR. There was a significant increase of survivin expression in patients as compared to controls (p < 0.001). The accelerated and blastic phases of the disease showed the highest significance (p < 0.001) than the chronic phase. Serum markers; survivin, IL6 and beta2M showed significant increase in the blastic phase, accelerated phase and chronic phase (p < 0.001, p < 0.001 and p < 0.001) respectively. A significant positive correlation was found between level of survivin expression and the other prognostic markers; high leucocytic count (r = 0.52), high peripheral basophile count (r= 0.81) and high peripheral blast cell count (r = 0.66), high level of serum survivin (r = 0.87), beta2 M (r = 0.76) and IL-6 (r= 0.90). On the other hand, a significant negative correlation was found between the survivin expression and hemoglobin concentration (r = 0.50). In conclusion, survivin is expressed in most cases of CML patients and its over expression is associated with bad prognosis. PMID- 20306658 TI - Comparative study between immunohistochemical grading and giardia genotyping among symptomatic and asymptomatic humans. AB - In the last years, multiple studies indicated the potential effectiveness of the polymerase chain reaction (PCR) for detection of Giardia in pathological specimens. By using the difference at the triose phosphate isomerase (tpi) gene locus, we investigated the genotype groups of Giardia lamblia isolated directly from fecal specimens collected from humans living in Dakahlia Governorate, Egypt. Immunohistochemical staining for detection of Giardia local antigenic and cellular immune-determinants focusing on CD4 and CD8 T-lymphocytes was also applied. The sensitivity of the ABC (avidine-biotin-peroxidase complex) immunoperoxidase technique for detection of the antigen was 97.3% and the specificity was 100%. Our study clearly demonstrated a highly significant difference between patients and controls as regards the grade of CD4 and CD8 lymphocyte infiltration (p < 0.001 for each correlation) but no significant difference was found between Giardia symptomatic and asymptomatic patients. Using the PCR technique, 89.3% sensitivity, 100% specificity and diagnostic accuracy of 92% were reached. Nevertheless, there was statistically insignificant difference between symptomatic and asymptomatic groups regarding the prevalence of different Giardia genotypes and the prevalence of CD4 and CD8 lymphocyte infiltration grading in different Giardia genotypes. PMID- 20306659 TI - Circulating chemokine eotaxin and chemokine receptor CCR3 in allergic patients. AB - Eotaxin is a chemokine with a selective eosinophil chemoattraction and its receptor is the chemokine receptor CCR3. The presence of CCR3 on Th2 lymphocytes is of particular interest. This work was performed to evaluate circulating level of chemokine eotaxin and CCR3 expression in allergic patients. It included 60 patients [23 (38.3%) with asthma, 20 (33.4%) with allergic rhinitis and 17 (28.3%) with skin allergy] and 12 controls. The level of plasma eotaxin & CCR3 expression on CD4+ T cells were determined by ELISA & flowcytometry respectively. Both plasma eotaxin level and expression of CCR3 on CD4+ T cells were higher in allergic patients than controls in different types of allergy. In conclusion, plasma eotaxin concentration is a candidate biological marker for the evaluation of allergic diseases. PMID- 20306660 TI - Pleural fluid IL-8 as an inflammatory mediator for discriminating transudates and exudates. AB - The differential diagnosis of pleural effusion is a frequent clinical problem. The possible role of pleural fluid cytokines in discriminating transudates from exudates has not been studied adequately. The aim of this study was to evaluate serum and pleural fluid levels of interleukin-8 (IL-8) and compare it with common biochemical parameters such as total protein lactate dehydrogenase (LDH). Forty patients with pleural effusion were studied. IL-8 was measured simultaneously in serum and pleural fluid using a commercially available ELISA kit. Standard laboratory methods were employed for biochemical parameters. Serum IL-8 levels were higher in the exudative group (8.1 +/- 0.2), but without statistical difference, when compared with transudate patients (6.8 +/- 0.1) (p > 0.05). Pleural IL-8 levels were significantly increased in exudate effusion when compared with transudate (26.6 +/- 3.7, 7.1 +/- 0.04 respectively, p < 0.001). In addition, a significant difference was found between pleural IL-8 in the malignant group (28.2 +/- 4.4) in comparison with the tuberculous group (21.1 +/- 2.9) (p < 0.01). Using ROC analysis, a pleural IL-8 cut off level of 19.7 pg/ml was found the best discriminating ratio in distinguishing exudates from transudates, with sensitivity of 100%, low specificity (from 50 to 66.7%) and good PPV (from 94.4 to 94.7%). Regarding pleural protein, the best discriminating value was 3 g/dl, while that for LDH was 200 IU/L. It is concluded that IL-8 could be considered as a sensitive, but not specific marker in differentiating pleural effusion into exudate and transudate, specially when used together with other criteria such as protein and LDH levels. PMID- 20306661 TI - Protective immune response of Mycoplasma gallisepticum vaccines in poultry. AB - Through a controlled vaccination study with artificial challenge, the present study was designed to evaluate the protective value of formalin, saponin or binary ethyleneimine inactivated Mycoplasma gallisepticum adjuvanted bacterins, in comparison with the efficacy of the live Mycoplasma gallisepticum "F" strain vaccine. Protective values of tested vaccines were compared by measuring antibody titers in sera of chicken at different intervals post vaccination by enzyme linked immunosorbent assay (ELISA), serum plate agglutination test and by scoring of sinus lesions after challenge with the virulent Mycoplasma gallisepticum "R" strain. The highest antibodies titer (P < 0.01) were recorded in the group of chicken vaccinated with the binary ethyleneimine inactivated vaccine that peaked at two weeks post-vaccination and remained elevated till the end of experiment. Meanwhile, the saponin-inactivated Mycoplasma gallisepticum elicited a comparable humoral immune response with that elicited by the binary ethyleneimine vaccine, the least immunizing effect was observed in the formalin inactivated Mycoplasma gallisepticum bacterins immunized chicken. Challenge of vaccinated birds was performed by intrasinus injection of 1 x 10(9) colony forming units of virulent "R" strain of Mycoplasma gallisepticum. While, similar degree of protection was afforded by binary ethyleneimine and saponin inactivated bacterins as well as the live "F" strain vaccine, the formalin-inactivated Mycoplasma gallisepticum bacterin showed lesser degree of protection. The obtained results indicated that inactivated bacterins could elicit a protective response in chicken, thus offering a new trend in the control and eradication of Mycoplasma gallisepticum from chicken flocks. PMID- 20306662 TI - Alterations in neutrophil surface expression of L-selectin (CD62L) and soluble L selectin (sL-selectin) in hemodialysis patients: relation to HCV. AB - High levels of L-selectin (CD62L) are a strong indicator of endothelial dysfunction, and atherosclerosis. Atherosclerosis is the leading cause of mortality and morbidity in hemodialysis (HD) patients. Whether HCV infection (highly prevalent in HD patients and also associated with alterations in adhesion molecules) would affect the leukocytic expression and/or the soluble form of L selectin in hemodialysis patients is unknown. Seventy-two HD patients, HCV positive (n=48) and HCV-negative (n=24) and 10 normal control were studied. Blood samples were obtained just prior to the start of the dialysis session (predialysis) and at the end of 15 min. of dialysis (intradialysis). The following tests were performed on all patients: HCV-RNA by RT-nested PCR, quantitative determination of sL-selectin by ELISA and neutrophil surface expression of L-selectin (CD62L) by flowcytometry. Both CD62L and sL-selectin were found to be significantly higher in HD patients as compared to normal controls irrespective to HCV. Fifteen minutes after start of the dialysis session both CD62L and absolute neutrophil count decreased significantly [CD62L, p < 0.0001 (HCV-positive), p= 0.03 in (HCV-negative), [neutrophil count, p < 0.0001 each], while sL-selectin showed a significant increase [p = 0.004 (HCV-positive), p = 0.006 (HCV-negative)]. These changes were unrelated to HCV status. A significant increase in CD62L in HCV-positive patients compared to HCV-negative ones in both pre and intradialysis samples was noted (p = 0.007, p = 0.02 respectively). However, no difference was observed in either sL-selectin or absolute neutrophil count between the two groups in the two tested time points. In conclusions, the increased levels of neutrophil-expressed and soluble forms of L-selectin in HD patients, and the intradialysis increase in sL-selectin and decrease in CD62L and neutrophil count are unrelated to HCV viremia. The association between HCV positivity and neutrophil expression of pre andintradialysis L-selectin point to a possible role of HCV that needs further studies. PMID- 20306663 TI - Plasma mammaglobin messenger RNA in breast cancer patients as an addition to serum tumor. AB - Breast cancer (BC) is the most frequent malignant tumor in women worldwide; its recurrence is a result of undetected metastasis present at the time of primary patient treatment. The detection of cell-free RNA in plasma and serum of human subjects has found increasing applications in the field of medical diagnostics.This study aimed at evaluating plasma mammaglobin mRNA as a useful tumor marker for the diagnosis and the detection of metastasis in breast cancer at the time of diagnosis either alone or in combination with conventional serum tumor markers CA15.3 and/or CEA. This study included 40 Egyptian females with primary breast cancer and 25 with different benign breast diseases. The BC group was classified into 24 patients with localized BC and 16 patients with metastases. All patients were subjected to routine laboratory investigations, estimation of serum CA15.3 and CEA by electrochemiluminescence immunoassay and detection of plasma mammaglobin mRNA by using nested reverse transcriptase polymerase chain reaction (RT-PCR). There was a significance increase in plasma mammaglobin mRNA expression, CA15.3 and CEA levels in BC group as compared to benign group (p < 0.001). No significant difference was observed between levels of plasma mammaglobin mRNA expression in patients with tumor's size or grade. No correlation was observed with plasma mammaglobulin mRNA levels and tumor size or grading, CEA and CA15.3. There was a significant difference (p < 0.05) and a positive correlation between CA 15.3 and CEA levels in patients with tumor size and grading. Expression of plasma mammaglobin mRNA has the highest sensitivity, specificity and diagnostic accuracy for both BC and BC with metastasis (75%, 92% & 81.5%) and (87.5%, 45.8% & 62.5%), respectively. To improve diagnostic efficacy of BC, the use of combined tests, expression of plasma mammaglobin mRNA and CA 15.3 improved the sensitivity, specificity and diagnostic accuracy to 90%, 80% & 86.2%, respectively; as well as in BC with metastasis to 100%, 79.2%, & 87.5%, respectively. In conclusion, plasma mammaglobin mRNA alone or in combination with CA15.3 may be used as a valuable noninvasive approach for the diagnosis and the detection of metastasis in breast cancer at the time of diagnosis. PMID- 20306664 TI - Role of interleukin-1beta and nitric oxide in the antiinflammatory dynamics of acetylsalicylic acid in carrageenan-induced paw oedema model. AB - The present study aimed to analyze the role of interleukin-1beta (IL-1beta) and nitric oxide (NO) in the development of peripheral acute inflammation in carrageenan-induced paw edema model in the presence/absence of acetyl salicylic acid (ASA). A 0.5 ml solution of 0.5%, 1% and 2% carrageenan was administered intraplantarly in right hind paw of adult Swiss mice. ASA was administered in a single dose of 200 mg/kg 1 hour before intraplantar injection of carrageenan. Paw volume, IL-1beta and nitrite levels in plasma and paw infiltrate and the total and differential white blood cells count were determined. Carrageenan administration induced a dose-dependent increase in paw volume, IL-1beta level in paw infiltrate and nitrite content in plasma. ASA exhibited a better anti inflammatory effect where 2% carrageenan was used as the inflammatory agent. Pre treatment with ASA resulted in increase in plasma IL-1beta level, decrease in IL 1beta level at the inflammation site and restoring plasma nitrite concentration to its normal range. Our results stressed on the role of IL-1beta and NO in the acute inflammation and suggested that the dose of carrageenan is the major determinant in the response to ASA. PMID- 20306665 TI - Psychiatric morbidity associated with some cytokines (IL-1beta, IL-12, IL-18 and TNF-alpha) among rheumatoid arthritis patients. AB - Psychiatric morbidity is common in rheumatoid arthritis (RA) patients and may affect disease activity and immunological markers. We studied the relationship of the psychiatric morbidity and immunological factors; the serum levels of Interleukin-1beta (IL-1beta), Tumor Necrosis Factor Alpha (TNF-alpha), Interleukin-18 (IL-18) and its inducer interleukin-12 (IL-12), and their impact on RA disease activity. Forty-two RA patients and 20 apparently healthy individuals as a control group were included in this study. Psychiatric morbidity was identified according to the International Classification of Disease, tenth version criteria (ICD-10). The Hospital Anxiety and Depression Scale (HADS) and the mental health Short Form 36 (SF-36) were applied for further analysis. Serum IL-1beta, IL-12, IL-18 and the TNF-a were measured using Enzyme-Amplified Sensitivity Immunoassays (EASIA) and were correlated with psychiatric morbidity and disease activity as measured by Health Assessment Questionnaire and Overall Status. Psychiatric morbidity was found in 40.48% of the studied patients, the most common psychiatric disorders among RA patients were depressive disorders and anxiety disorders. The SF-36 score was closely correlated to the anxiety and depression score (P < 0.001). RA patients showed high levels of IL-1beta, IL-12, IL-18 and TNF-alpha than the control group. There was a significant correlation between psychiatric morbidity, serum levels of IL-1beta, IL-12, IL-18, TNF-alpha and disease activity measurements. We have to view rheumatoid arthritis as a psycho-immumological disorder rather than an autoimmune disease. Furthermore, the studied cytokines may be a novel target for therapeutic intervention of rheumatoid arthritis and its psychiatric morbidity. PMID- 20306666 TI - Pro-inflammatory cytokines and depression in patients with acute leukemia. AB - The prevalence of depression among patients diagnosed with cancer is higher than general population and is associated with faster tumor progression and shorter survival time. Cytokines whose primary function is to act as signaling molecules of the immune system have recently also been implicated in the pathogenesis of depression. The aim of present study was to investigate the relation between pro infammatory cytokines [Interleukin-6 (IL-6) and Tumor Necrosis Factor-alpha (TNF alpha)], depression and stressful life events in patients with acute leukemia. Twenty eight patients (18 males and 10 females) suffering from acute leukemia participated in this study. Their mean age was 33.3 +/- 12.1 years. They were subjected to psychiatric assessment using The Beck Depression Inventory (BDI), Holmes and Rahe Social Readjustment Scale, The Perceived Stress Scale (PSS) and The Brief Fatigue Inventory (BFI). Measurement of IL-6 and TNF-a genes expression in peripheral blood mononuclear cells was done using real-time PCR. Results revealed statistically significant elevation in the level of IL-6 gene expression, fatigue and perceived stress among depressed patients compared to none depressed group. The same results were obtained when comparing patients exposed to moderate or severe stressful life events compared to those exposed to none or mild stressful life events. Although, TNF-a gene expression was not associated with depression or stressful life events, it was associated with acute myeloblastic leukemia (AML). IL-6 gene expression was much higher among patients with AML than acute lymphoblastic leukemia (ALL), but the difference did not reach statistical significance. These findings support the hypothesis that IL-6 might be involved in the etiology and symptomatology of depression in cancer patients. The development of biologic therapies targeting IL-6 may raise the possibility of simultaneously countering the severe effects of depression. PMID- 20306667 TI - Heamostatic and genetic predisposing factors for stroke in children with sickle cell anemia. AB - Sickle cell disease (SCD) is a group of genetic disorders characterized by the production of the abnormal hemoglobin S (HbS). Sickle cell anemia (SCA) is the most common type of SCD and represents the homozygous form, in which the individual inherits a double dose of the abnormal gene that codes for hemoglobin S. This study was done to detect cases of silent and clinically overt strokes in children with sickle cell anemia (SCA) and examine predisposing factors for stroke development. The study included 20 children with clinically and hematologically confirmed SCA and 10 controls. They were divided into two groups, group I; included 10 steady state cases and group II; included 10 cases with thrombotic crisis. All subjects were subjected to full clinical examination, measurements of plasma level of: fibrinopeptid A (FPA), thrombin-antithrombin III (TAT), fibrin degradation product (D-dimer) and serum level of platelet endothelial cell adhesion molecule-1 (PECAM-1), and analysis of the ACE gene polymorphism by polymerase chain reaction (PCR). Patients were further subjected to Brain computed axial tomography (CT) scan and/or magnetic resonance imaging (MRI) as well as electro-encephalographic studies (EEG). Silent ischemic brain infarction as evidenced by CT scan and/or MRI was present in one patient in group I (10%) and one patient in group II (10%). On the other hand, two patients in group II (20%) showed clinically overt strokes. Thus, 4 children had silent or clinically overt stroke and the remaining 16 were non-stroke cases. Laboratory results showed that the levels of FPA, TAT, D-dimer and PECAM-1 were significantly elevated in SCA patients both in the steady and crisis states as compared to control, with more evident significant elevation in group II (thrombotic crisis) as compared to group I (steady state). The stroke group showed significant elevation; FPA, TAT, D-dimer and PECAM-1 as compared with non stroke group. The PCR results showed that the frequencies of both DD genotype and D allele of ACE gene in the thrombotic crisis are significantly higher than in the control group and that all stroke children are of DD genotype. In conclusion, significant increase in FPA, TAT, D-dimer and PECAM-1 levels as well as the presence of ACE D allele of the ACE gene are significant predisposing factors for stroke in children with SCA. Regular follow-up by thorough neurological examination and neuro-imaging studies for early detection of silent brain infarction is recommended. PMID- 20306668 TI - TGF-beta1 and C-erb-B2 neu oncoprotein in Egyptian HCV related chronic liver disease and hepatocellular carcinoma patients. AB - Transforming growth factor beta (TGF-beta), a pro-fibrogenic cytokine, has several polymorphism in humans with difference in activity levels. Hepato carcinogenesis involves alterations in the action of protooncogenes such as the; neu (C-erb-B2) oncogene. Overexpression of the neu-oncogene has been implicated in experimental cellular transformation and tumorigenesis in a wide range of human cancer. We examined TGF-beta1 and C-erb-B2 mRNA expression and their protein levels in hepatitis C virus (HCV) patients and those developing Hepatocellular carcinoma (HCC). Sixty patients (30 HCV and 30 HCC) and 30 controls were enrolled. HCV patients were classified into mild, moderate, marked and no fibrosis. HCC patients were categorized into grade I, II, Ill. TGP-beta1 and C-erb-B2 expression were studied. Messenger RNA was extracted using the guanidinum thiocyanate phenol chloroform method, and used of RT-PCR. Protein serum levels were estimated by (EIA). Significant difference were obtained when comparing TGF-bet1 and C-erb-B2 mRNA in HCV and HCC P = 0.0076, and controls. The HCV group revealed significant difference with C-erb-B2 but not TGF-B1 mRNA as compared to controls P < 0.005 and P > 0.05 respectively. Serum protein levels demonstrated difference increase significance shown when comparing their levels in both studied groups P < 0.001, P < 0.05 respectively and when compared to controls (P < 0.001). TGF-beta1 serum levels in HCV patients showed increase with degree of fibrosis (P = 0.003) while, C-erbB-2 serum levels showed no significance (P = 0.089). In different grades of HCC patients, TGF-beta1 levels showed no significant difference (P = 0.769). However, C-erb-B2 levels revealed significant difference (P = 0.002) between grade I & III and grade II &. Ill (P < 0.001). Positive correlations to protein serum level were obtained with TGF beta1mRNA in HCV group, while, C-erb-B2 mRNA in HCC patients. In conclusion, TGF beta1 upregulation in HCC suggests its role in hepatic carcinogenesis. Elevated expression of C-erb-B2 may reflect pre-neoplastic liver cell proliferation, cellular necrosis associated with chronic liver disease and alternatively from HCV carcinogens which enhance malignant transformation. Correlation of both parameters with their protein levels might rise using their antibodies in immunotherapy for HCC. PMID- 20306669 TI - Effect of mouse strain on humoral responses to Schistosoma mansoni irradiated cercariae vaccine. AB - In murine schistosomiasis, the highest level of resistance to cercarial challenge is obtained by vaccination with radiation-attenuated (RA) cercariae. To identify candidate vaccine antigens relevant to the vaccine model, we examined by ELISA and Western blot parasite antigens recognized by antibodies from mice vaccinated with Schistosoma mansoni RA cercariae. To optimize recognition, several factors that may influence protection level in this model were assessed; specifically, we examined the effect of (i) single versus double vaccinations with RA cercariae, and (ii) the genetic background of mouse strains, high-responder versus moderate responder. We found that the number of vaccinations alters antibody specificity and modifies relative antibody titers against particular tegumental antigens. RA cercariae vaccine appeared to be immunogenic against supernatant 2 (Sup.2) and surface membrane pellet (SMP) tegumental target antigens in different mouse strains. However, the immunogenicity against Sup.2 was higher than that against SMP, moreover, general increase in antibody response with boosts. Also, the present study aims to provide information on the molecules recognized by RA cercariae vaccine sera derived from different inbred mice, several bands in Sup.2 immunoblots were recognized with variations in the number and pattern of bands observed. In conclusion, RA vaccine is effective vaccine against schistosomiasis. PMID- 20306670 TI - Evaluation of the diagnostic potential of different immunological techniques using polyclonal antibodies against Fasciola gigantica excretory/secretory antigens in sheep. AB - The early detection of Fasciola antigens (Ags) in serum or stool could be more valuable in diagnosis as early treatment would be applied before irreparable damage occurs. In this study, fresh adult Fasciola gigantica (F. gigantica) worms were cultivated for 16 hrs. Excretory/secretory (E/S) Ags were extracted from the culturemedium and used to raise rabbit antibodies (Abs) to Fasciola. The purified Abs were then used in sandwich ELISA (S-ELISA) to detect Fasciola Ags in serum and stool samples from a total of 152 sheep, and sandwich-Dot-ELISA (S-D-ELISA) for the serum samples. Gross inspection of liver for flukes or other parasites was performed and results of parasitological stool examination were recorded. Accordingly, sheep were divided into healthy control group (25 sheep), Fasciola positive group (97 sheep) and other helminthic infection groups (30 sheep). S ELISA for serum samples showed 91.9% sensitivity and 89% specificity. Fasciola Ags, detected in serum of sheep by S-D-ELISA, showed 97.2% sensitivity and 95% specificity and coproantigens detected by S-ELISA, showed 95.8% sensitivity and 92.7% specificity. Although, the specificity of stool examination was higher than that recorded for serum, the sensitivity of ELISA techniques to diagnose Fasciola Ags was higher than that recorded for parasitological examination. It is concluded that, S-D-ELISA has better sensitivity and specificity than S-ELISA for both stool and serum, and may prove useful for field applications. PMID- 20306671 TI - Reliability of serum procalcitonin concentrations for the diagnosis of sepsis in neonates. AB - The evaluation of tests for neonatal sepsis is important because the infection may present a very serious threat to the baby. Extensive literature exists on single laboratory test or combinations of tests, as well as tests used together with risk factors and/or clinical signs, to diagnose neonatal sepsis. In many instances, the results of the evaluations have been conflicting. It has recently been suggested that serum procalcitonin (PCT) is of value: in the diagnosis of neonatal sepsis, with varying results. This study was designed to determine the reliability of PCT concentrations as a new marker for the diagnosis of early neonatal sepsis of vertical transmission comparing to the traditional inflammatory mediators, such as interleukin-6 (IL-6) and C-reactive protein (CRP) values. The current study included 69 newborn babies. After full history and clinical examination, they were classified into 2 groups: Group 1, included 27 of asymptomatic newborn infants admitted during the first 24 h of life to the neonatal unit because of prematurity, low birth weight. They had no clinical signs of sepsis during their first week of life and had a negative blood culture, and they did not receive antibiotic treatment. The second group: Group 2, included 42 symptomatic neonates who were admitted to the neonatal care unit and were evaluated for sepsis during the first 48 h of life, they were subclassified into twosubgroups: group 2A; included 22 neonates of confirmed vertical neonatal sepsis, defined as they had at least three clinical signs of infection with culture proven sepsis, and group 2B included 20 neonates of vertical clinical sepsis (they had at least three clinical signs of infection) with negative blood culture. Blood sampling for blood culture, complete blood count, blood gases and blood chemistry, additionally, CRP, serum IL-6 and PCT were measured. The microbial organisms isolated from the blood culture of group 2A; Escherichia coli was isolated from 9 cases, staphylococcus aureus from 6 cases, staphylococcus epidermidis from 2 cases, group B streptococci (GBS) from 2 cases, ureaplasma from 2 cases and one case was GBS positive mother. The comparison between the studied groups revealed that, white blood cell counts (WBCs) and CRP levels were significantly increased in group 2A more than in group 1 and group 2B. While in group 2B the WBCs not differed from group 1 but CRP differed from group 1. IL-6 and PCT values were significantly increased in group 2A more than in group 1 and group 2B. Furthermore in group 2B both were significantly increased as compared to group 1. For the diagnosis of neonatal infection, at cutoff >1.5 ng/ml, PCT give a sensitivity of 92.9%, specificity of 85.2%, positive predictive value (PPV) of 84.8%, and negative predictive value (NPV) of 76.7%. At a cutoff >140 ng/ml, IL-6 gives a sensitivity of 76.2%, speCificity of 70.4%, PPV of 64%, NPV of 63.3%. However, at a cutoff >12 mg/L, CRP gives a sensitivity of 88%, specificity of 77.8%, PPV of 77.1%, NPV of 70%. We conclude that the serum PCT concentration showed a good diagnostic value for the early detection of neonatal sepsis of vertical transmission comparing with the other traditional markers of inflammations, thus may facilitate early therapeutic intervention in those high risk group. PMID- 20306672 TI - Diagnosis of Entamoeba histolytica in symptomatic children, Jeddah City, Saudi Arabia. AB - Amebiasis is one of the most common parasitic infections worldwide. Entamoeba histolytica and Entamoeba dispar are two morphologically indistinguishable human protozoa parasites that are genetically distinct species. Differential diagnosis of E. histolytica (pathogenic) and E. dispar (non-pathogenic) is essential both for treatment decision and public health knowledge. Stool samples from 500 randomly selected children complaining of gastroenteritis were examined microscopically by direct wet smear and subjected to detection of E. histolytica antigen by ELISA using TechLab E. histolytica II test. E. histolytical E. dispar were also identified at molecular level by targeting the 166 bp, and 752 bp sequences of the 18Sr RNA gene of E. histolytica and E. dispar respectively using polymerase chain reaction technique (PCR). The overall prevalence of E. histolytica/dispar by microscopic examination was 30/500 (6%). E. histolytica was positive in 161500 (3.2%) by antigen detection ELISA technique, whereas 10 samples were not detected microscopically. PCR was able to confirm the presence of E. histolytica in 13/16 cases whereas the 3 samples recorded negative were positive by ELISA; even so there was a good agreement k = 0.86 between the two techniques. In conclusion, stool antigen detection test by ELISA is recommended over PCR in detecting and confirming E. histolytica amoebic enteritis. PMID- 20306673 TI - Prevalence and prognostic significance of murine double minute protein-2 overexpression and P53 gene mutations in childhood acute lymphoblastic leukemia. AB - The murine double minute protein-2 (MDM-2) oncogene is a determinant of embryogenesis, tumorigenesis, and cell cycle progression. The effects of MDM-2 on these processes depend, in part, on its ability to inactivate the p53 tumor suppressor gene. Our goal was to determine whether MDM-2 protein overexpressions or p53 gene mutations are a frequent event in poor outcome pediatric acute lymphoblastic leukemia (ALL). This work was conducted on 46 children with ALL (31 males and 15 females) with age range 2-18 years, 18 children with matched age and sex were enrolled in the study as a control group. The MDM-2 expression by flowcytometry and p53 gene status by PCR were determined in peripheral blood or bone marrow of ALL children (at initial diagnosis) and also of control group. The ALL children were treated by the modified BFM 76179 protocol of therapy, 29 patients (63%) achieved complete remission, while 17 patients (37%) were subsequently failed to achieve complete remission or relapsed within 6 months of achieving complete remission (CR). MDM-2 was significantly overexpressed in 15 ALL patients (32.6%), compared to that of healthy controls, 4 of them (4/15), were out of 29 cases of CR (13.8%), and the other 11 cases were out of 17 relapsed cases (64.7%). In contrast to overexpression of MDM-2, the mutation of p53 was detected in 6 (13%) out of 46 ALL patients at the initial time of diagnosis, 3 of them (10.3%) were out of 29 cases of CR and the other 3 cases (17.6%) were out of 17 of relapsed group, which is significantly higher than CR group (P < 0.05). In relapsed group, 2 patients out of 3 cases with p53 mutation were MDM-2 negative, also, all 3 cases of mutant P53 among patients in CR were negative MDM2. A positive correlation was found between the MDM-2 overexpression and initial WBCs count, blast cell counts in peripheral blood and presence of CNS blasts (p < 0.05, p < 0.05 and p < 0.05 respectively). These results indicate that MDM-2 is overexpressed in a significant number of childhood ALL, it is more frequent in relapsed cases and its frequency is not related to p53 status. Thus measuring of MDM-2 as a bad prognostic marker even in cases with non mutant P53 is very important. Moreover, MDM-2 may be a potential molecular target for production of new cancer therapy. PMID- 20306674 TI - Anticardiolipin antibodies in diabetic patients: an additional risk factor in the pathogenesis of diabetic retinopathy. AB - The natural history and aetiogenesis of diabetic retinopathy (DR) are still not completely understood. Autoantibodies against endothelial antigens could be responsible for initiating vascular injury and could be a marker of endothelial dysfunction. In this study, the prevalence of anticardiolipin (aCL) antibodies in patients with high risk criteria proliferative diabetic retinopathy (PDR) were determined to investigate whether aCL antibodies might be relevant to the pathogenesis of DR. We studied 34 diabetic patients, free of DR, and 36 patients with PDR with high risk criteria (HRC). aCL antibodies (IgG and IgM) were determined using ELISA technique. There was a significant prevalence of aCL antibodies in type 1 diabetics having PDR with HRC (27.8%) while it was only 6.25% of type 2 diabetics having PDR with HRC. All patients who were positive for aCL antibodies had PDR with HRC. The difference was statistically significant. These preliminary findings suggest that aCL antibodies could represent an additional risk factor for PDR acting as a link between the immunological haemostatic systems. PMID- 20306675 TI - Pro-inflammatory and anti-inflammatory cytokines profile in rheumatoid arthritis patients. AB - Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by severe joint deformities due to bony erosions and tendon damage. Cytokines are protein mediators of inflammation and are produced as a result of the activation of various cellular reactions. They are the final mediators and/or regulators of the inflammatory process. Cytokines such as TNF-alpha and IL-6, play key roles in driving the inflammation and synovial cell proliferation that characterize rheumatoid arthritis and joint destruction. Sera from 58 RA patients were analyzed for TNF-alpha, IL-6, IL-10, TGF-beta, sTNF-R 1 and sTNF-R2 using ELISA. The proinflammatory cytokines TNF-alpha and IL-6 were significantly elevated in RA patients, while TGF-beta, an immunomodulatory cytokine, was elevated in control individuals. Assays of TNF receptors, sTNF-R1 and sTNF-R2, were noted to be significantly elevated in RA patients when compared to control. Our data indicate that local production of cytokine inhibitors is capable of diminishing cytokine and disease activity thereby may improve signs, symptoms and quality of life for patients with RA. PMID- 20306676 TI - Does pre-transplant in vitro detection of anti-endothelial cell antibodies predict renal allograft outcome? AB - Endothelial cells lining the vasculature proved to be the target for immune mediated assault, conceivably through the so-called anti-endothelial cell antibodies (AECA). The aim of this work was to detect the AECAs, and to show its correlation with kidney allograft rejection and graft survival. The study included 60 patients who underwent live-donor kidney transplantation. Inclusion criteria included: first kidney transplants, PRA titer less than 5%, causes of ESRD not including vasculitis or systemic lupus erythematosus and age >18 years. According to the presence or absence of AECA, patients were classified into two groups: group I consisted of forty patients with positive AECA and group II included twenty patients with negative AECA. Serum creatinine level in the AECA positive group increased significantly at 1 month and 1 year (p = 0.04) following renal graft. The overall incidence of acute rejection (AR) was not significantly different in both groups (P = 0.5). However, the frequency of AR episodes was observed more in the positive than in the negative AECA group (P = 0.04). Chronic rejection was significantly higher in patients with positive than in the negative AECA group, 15% vs. 5%) (P = 0.03). Differences in graft survival were found to be 91% vs. 100% after 1-year and after 5-years 84% vs. 91% (P = 0.04) in the AECA positive and negative groups respectively. In conclusions, our results suggest that the presence of a significant association between the occurrence of AECAs and multiple graft rejection and inferior long-term graft survival in kidney transplants. Testing for AECA prior to kidney grafting would be informative in identifying patients at high risk for immunological graft loss. PMID- 20306678 TI - Prognostic significance of CEBPA mutations and BAALC expression in acute myeloid leukemia Egyptian patients with normal karyotype. AB - Cytogenetic aberrations are important prognostic factors in acute myeloid leukemia (AML). However, about 50% of newly diagnosed acute myeloid leukemia (AML) cases have normal karyotype. These patients are very heterogenous with respect to acquired gene mutations and gene expression changes. The identification of these genetic alterations may lead to improved prognostification and generation of novel risk-adapted therapies. The aim of this work was to study the prognostic impact of mutations in the myeloid transcription factor gene CEBPA (for CCAAT/enhancer binding protein-alpha) and expression of the BAALC gene (for brain and acute leukemia, cytoplasmic), a novel gene involved in leukemia, in 38 adults with AML and normal cytogenetics. Screening for mutations of CEBPA gene was assessed using PCR-single-strand conformation polymorphism (PCR-SSCP), and BAALC expression was determined by real-time reverse transcriptase polymerase chain reaction in blood or bone marrow samples. CEBPA mutations were found in 7 (18.4%) of 38 patients, 36.8 % (14 of 38) had low BAALC expression and 63.2 % (24 of 38) had high BAALC expression. Patients with CEBPA mutations had favorable course of their disease. They had higher rate of complete remission (CR) (85.7 % vs 51.6 %; P = 0.108), lower incidence of relapse (0% vs. 41.9%; P = 0.038). Disease free survival (DFS) and overall survival (OS) were significantly longer for patients with CEBPA mutations compared with patients without mutations (mean 13.65 +/- 5.41 vs. 7.32 +/- 4.33 months, P = 0.047; mean 15.32 +/- 6.5 vs 8.5 +/- 3.21 months, P = 0.039; respectively). Compared to low BAALC expressers, high BAALC expressers had lower incidence of CR (50% vs 71.4%; P = 0.171), higher incidence of relapse (50% vs. 14.3%; P = 0.029), and showed significantly shorter DFS (mean 7.5 +/- 2.12 vs. 11.67 +/- 4.6 months, P = 0.038) and inferior overall survival (mean 9.1 +/- 3.52 vs. 13.22 +/- 4.21 months, P = 0.024). On multivariable analysis, wild-type CEBPA as well as high BAALC expression were confirmed as independent risk factors predicting inferior DFS (CEBPA, hazard ratio 0.066, P = 0.001; BAALC, hazard ratio 3.98, P = 0.003) and inferior OS (CEBPA, hazard ratio 0.125, P = 0.002; BAALC, hazard ratio 4.215, P = 0.001). Data obtained in this study suggest that CEBPA mutation status and BAALC expression are important prognostic factors in AML patients with normal cytogenetics and their incorporation into novel risk-adapted therapeutic strategies may improve the currently disappointing cure rate of this group of patients. PMID- 20306677 TI - Serum levels of soluble CD30 in patients with atopic dermatitis: correlations with age, disease duration and severity. AB - Atopic dermatitis (AD) is a chronic, inflammatory skin disease in which a pathogenetic role of Th2 cells has been supposed. CD30 molecule has been linked to Th2 responses. Elevated serum levels of soluble CD30 (sCD30) are associated with atopic disease, however, little is known about the effect of age, duration of disease, family history (FH) of atopy and scoring atopic dermatitis index (SCDRAD) on the levels of serum sCD30 in AD patients. In the present study, the serum level of sCD30 in 40 patients with AD and 15 non atopic persons, matched for sex and age were studied. Serum sCD30 levels were significantly higher in AD patients (23.1-83.9 IU/ml) than in healthy control (7.5-14.5 IU/ml) (P < 0.001). The sCD30 levels correlated positively with the severity of AD as assessed by SCORAD (r = 0.45; P = 0.004). Levels were higher in AD patients with +ve FH than those with -ve FH (P > 0.05) and in AD patients with shorter disease duration than longer duration (P > 0.05). In conclusion the presence of high levels of sCD30 in AD patients support the view that Th0/Th2- type response predominates in AD patients. The correlation observed with the clinical score indicates a role of sCD30 as a marker of disease severity in AD patients. PMID- 20306679 TI - Epstein-Barr virus-transformed B-cells as efficient antigen presenting cells to propagate Aspergillus-specific cytotoxic T-lymphocytes. AB - To overcome the cytotoxic T-lymphocytes (CTL) expansion limitations imposed by the lack of sufficient dendritic cells (DC) alternative sources of autologous antigen presenting cells (APC) such as Epstein-Barr virus (EBV)-transformed B lymphoblastoid cell lines (BLCL), which are easy to establish in vitro, have been considered and studied in the present work. Non-adherent peripheral blood mononuclear cells of three healthy donors were repeatedly primed with autologous Aspergillus fumigatus commercial culture-filtrate antigen-pulsed fast monocyte derived DC (Aspf-CFA-DC) alone, Aspf-CFA-pulsed BLCL (Aspf-CFA-BLCL) alone or Aspf-CFA-BLCL after one, two, or three primings with Aspf-CFA-DC (1DC/BLCL, 2DC/BLCL or 3DCIBLCL; respectively). After 5th priming, lines generated by Aspf CFA-BLCL only showed strong/weak lytic activity for EBV/Aspf; respectively. Aspf specific lytic activity in all donors was increased by increasing the number of primings with Aspf-CFA-DC before switching to Aspf-CFA-BLCL (18.20 +/- 1.65% versus 35.67 +/- 1.02% and 40.03 +/- 1.41% in bulk cultures generated by 1DC/BLCL versus 2DC/BLCL and 3DC/BLCL, respectively). Bulk cultures generated by Aspf-CFA BLCL after at least two primings with Aspf-CFA-DC showed approximately the same Aspf-specific lytic activity, effector cell phenotype, expansion level and percentage expression of IFN-gamma, CD69 and CD107a without any significant differences (p > 0.05) as standard bulk cultures generated by only Aspf-CFA-DC. Thus, this study explored the use of a combined DC/BLCL protocol to establish/propagate Aspf-specific CTL for adoptive immunotherapy to prevent or treat invasive pulmonary aspergillosis. PMID- 20306680 TI - Plasma and synovial fluid adipocytokines in patients with rheumatoid arthritis and osteoarthritis. AB - Adipocytokines are hormone and cytokine like substances produced mainly from white adipose tissue. A relation between plasma adipocytokines and many inflammatory disorders including rheumatoid arthritis (RA) had been investigated. This work was done to investigate the systemic behavior of the main adipocytokines at the plasma level as well as its local behavior at the synovial fluid level in patients with RA and osteoarthritis (OA). The study had been conducted on 32 patients with RA and 18 patients with OA. Paired blood and synovial fluid samples had been collected from all patients and level of plasma and synovial fluid (SF) leptin, adiponectin and resistin had been quantitated by enzyme linked immunosorbent assay (ELISA). Results had been compared between RA group and OA group. Adipocytokines had also been compared in patients with erosive and non-erosive disease and had been related to clinical and laboratory markers of activity. Plasma resistin and BMI-corrected plasma leptin were significantly higher in RA group. Female patients showed significantly higher plasma leptin, even after correction to BMI. Studied SF adipocytokines were significantly higher in RA group and correlated positively with synovial fluid WBCs. Comparing plasma and SF results showed a significant increase in SF resistin especially in RA group and a significant drop of SF adiponectin especially in OA group. In conclusion, Adipocytokines are probably involved in inflammatory and degenerative articular disease. The different behavior between plasma and SF would suggest a pro-inflammatory role for resistin and chondro protective role for adiponectin. PMID- 20306681 TI - Fractionation of organ extracts of Culex pipiens mosquitoes for the isolation of active components that impair biological parameters of the insect. AB - The previous phase of the present study revealed that when crude extracts of Culex pipiens midgut, ovaries, and salivary glands are injected into New Zealand White (NZW) rabbits (Oryctolagus cuniculus), rabbits immunized with midgut extract exert the greatest negative impact on adult Cx. pipiens survival and fecundity. This study was conducted to further our understanding of the immunogenic nature of the aforementioned antigenic preparations, thus providing data for the ultimate goal of developing a vaccine against the numerous Cx. pipiens-vectored diseases that affect human populations throughout the world. Extracts of Cx. pipiens midgut, ovaries, and salivary glands were fractionated using Sodium Dodecyl Sulphate Polyacrylamide Gel Electrophoresis (SDS-PAGE). The high (> 80.0 to >106.0 kDa) and low (< 18.5 kDa) molecular weight (MW) fractions of midgut extract, high MW fractions (75.0 - <106.0 kDa) of salivary gland extract, and low MW fraction (27.5 kDa) of ovary extract were excised, and used to immunize rabbits. Following immunization, anti-sera from all immunized rabbits were assayed for antibody response using Enzyme-Linked Immunosorbent Assay (ELISA), Enzyme Immunoblot transfer (EIB), and Indirect Fluorescent Antibody Techniques (IFAT). These assays resulted in both high and low MW fractions of midgut extract, with special reference to the midgut extract low MW fraction (18.0 kDa), eliciting the strongest humoral responses in immunized hosts. When Cx. pipiens were fed on rabbits immunized with the low MW fractions of midgut extract, the fecundity and survival rates were significantly less than those of mosquitoes fed on rabbits immunized with the high MW fractions of midgut extract and control rabbits (P < 0.001). It is concluded that, the low MW fraction of midgut extract is highly immunogenic, and the antibody response of immunized rabbits contributes to a significant disturbance in the life cycle of Cx. pipiens and their progeny. This impairment of feeding behavior and reproduction, in turn, could interfere with pathogen transmission. PMID- 20306682 TI - Modulation of IL-4 level by fludarabine and its relation to apoptosis in chronic B-cell lymphocytic leukemia. AB - Accumulation of malignant B-lymphocytes in chronic B-cell lymphocytic leukemia (B CLL) is mainly attributed to reduced apoptosis rather than increased proliferation rate. Interleukin-4 (IL-4) has been proved to be involved in the survival mechanisms of B-cells as well as protection of B-CLL cells against spontaneous or drug induced apoptosis. Fludarabine is one of purine analogs and the current standard treatment for B-CLL, which has been proved to induce apoptosis in normal and malignant lymphocytes. We investigated the effect of ex vivo treatment of peripheral blood lymphocytes (PBLs) with Fludarabine on apoptosis and IL-4 production in untreated patients with B-CLL. The study was conducted on 15 recently diagnosed B-CLL patients and 15 normal healthy control subjects. PBLs were isolated and cultured in complete culture media without and with the addition of 1 microM/ml Fludarabine for 48 hrs. Harvested cells were assessed by flowcytometry for apoptosis and IL-4 production using staining with Annexin-V/PI and specific monoclonal IL-4 antibody, respectively. RESULTS: Fludarabine significantly increased the rate of in vitro PBLs' apoptosis in both B-CLL patients and normal subjects (3.81 +/- 1.98% and 4.11 +/- 2.14% without Fludarabine vs 14.78 +/- 7.83% and 9.99 +/- 5.60% with Fludarabine, respectively). However, the cytotoxic effect of Fludarabine was significantly higher in B-CLL patients than normal control subjects. Cytolasmic IL-4 content, as reflected by mean flouresence intensity (MFI), as well as percentage of IL 4+ve PBLs in absence Fludarabine were nearly the same both in B-CLL patients (20.28 +/- 14.34 & 2.97 +/- 1.48%, respectively) and normal subjects (27.75 +/- 14.44 & 2.58 +/- 1.27% respectively), with no significant difference. Corresponding values were significantly increased in both B-CLL patients (34.46 +/- 22.95 & 15.08 +/- 8.17%, respectively) and normal subjects (40.15 +/- 17.11 & 17.05 +/- 8.74%, respectively) when PBLs were co-cultured with Fludarabine. However, no significant difference was observed when studied groups were compared to each other. No correlation was observed between the intracellular IL-4 content or percentage of IL-4+ve PBLs and Fludarabine-induced apoptosis. In conclusion, Floudarabine could induce apoptosis and IL-4 production in B-CLL patients. Further studies on large cohort population is recommended to clarify the apoptotic effect of Fludarabine. PMID- 20306683 TI - Antibody screening in repeatedly transfused patients. AB - The purpose of pretransfusion compatibility testing is to prevent immune mediated hemolytic transfusion reactions. Our study aimed to evaluate the gel test for detection of clinically significant antibodies in repeatedly transfused patients. We investigated 200 thalassemic patients in whom, blood group, Rh-D, Rh phenotype determination, antibody screening and identification were done using an ID Microtyping System. Red cell alloantibodies were detected in 21 patients (10.5%). Among these patients, Anti-E was detected in 5 (23.8%), anti-D in 4 (19%), anti-K in 4 (19%), anti-e in 3 (14.3%) and each of anti-Fy(a), anti-Js(a), anti-Lu(a), anti-N and anti-s in one patient (4.8%). Anti-E showed the highest frequency in the 21 positive cases that developed clinically significant antibodies. The study revealed statistically significant correlation between development of transfusion reactions, frequency of blood transfusion and the duration of blood transfusion with the incidence of development of clinically significant alloantibodies. It is concluded that the gel test is an easy, quick and reliable method for detecting clinically significant antibodies. Antibody screening and identification is recommended prior to transfusion to detect if there is blood group incompatibility other than the ABO and Rh. PMID- 20306684 TI - Cytokine gene polymorphisms in Egyptian cases with brain tumors. AB - Cytokines are proposed to play important roles in brain tumor biology as well as neurodegeneration or impaired neuronal function. To evaluate the association of polymorphisms of cytokine genes with brain tumors in Egyptian patients. This study included 45 cases affected by brain tumors. Their median age was 45, diagnosed as 24 benign cases and 21 malignant cases, and their sex included 20 males and 25 females. They were taken from the cases presenting to the Neurosurgery Department of Mansoura University Hospital, Egypt. Cases genotypes were compared to 98 healthy unrelated controls from the same locality. DNA was amplified using PCR utilizing sequence specific primers (SSP) for detection of polymorphisms related to TNF-alpha(-308) (G/A), IL-10(-1082) (G/A), IL-6(-174) (G/C) and IL-1Ra (VNTR). Cases affected with benign brain tumors, showed a significant higher frequency of IL-10(-1082) A/A genotype (OR = 8.04, P < 0.001), IL-6(-174) C/C genotype (OR = 6.3, P < 0.001) and TNF-alpha(-308) A/A (OR = 4.7, P < 0.05) with a significant lower frequency of IL-10(-1082) G/A genotype (OR = 0.1, P < 0.001), IL-6(-174) G/C (OR = 0.2, P = 0.001) and TNF-alpha(-308) G/A was found significantly low among the same groups (OR = 0.2, P < 0.001) compared to controls. On the other hand these cases have shown no significant difference regarding the distribution of IL-1Ra VNTR genotype and allele polymorphism compared to controls. Although the levels of different studied cytokines were not determined simultaneously in the serum, these cases are expected to have lower levels of IL-10 and high levels of TNF-alpha being homozygous for IL-10(-1082) allele A (low production allele) and TNF-alpha(-308) A (high production allele). The frequency of cytokines genotype and allele in malignant brain cases and controls. Malignant cases, on the other hand, showed significant higher frequency of IL-6(-174) C/C genotype (OR = 4.8, P < 0.05) and both TNF-alpha(-08) A/A (OR = 4.9, P < 0.001) and G/G (OR = 4.7, P < 0.05) genotypes as compared to controls. In the mean time these cases have shown a significant lower frequency of genotypes of IL-6(-174) G/C (OR = 0.2, P < 0.05) and TNF-alpha(-308) G/A (OR = 0.1, P < 0.05) compared to controls. On the other hand, these cases have not shown any statistical significant difference of polymorphic genotypes or alleles related to IL-10(-1082) (G/A) and IL-Ra VNTR genes compared to controls. Comparing studied genotype frequencies among benign and malignant brain tumor cases no significant difference was found in the frequencies of all studied genotypes and alleles with a non significant trend for the benign cases to have higher frequency of IL-10(-1082) AA genotype. In conclusion, cytokine gene polymorphisms have a certain pattern among brain tumor cases and can be considered a genetic marker of potential value in counseling and management. PMID- 20306685 TI - Dual color FISH on CBF primary acute myeloid leukemia. AB - In acute myeloid leukemia (AML), clonal chromosomal aberrations constitute markers of diagnostic value and the molecular characterization of numerous abnormalities has greatly improved the understanding of the biology of distinct subtypes of the disease. Two of the most common recurring chromosomal abnormalities in AML are t(8;21) and inversion of chromosome 16 or its variant which belong to core binding factor (CBF) AML group. We aimed to compare between cytogenetics and dual color Fluorescence In Situ Hybridization (FISH) regarding their sensitivity for detection of CBF AML associated translocations including t(8;21) and inv(16)/t(16;16). Fifty five consecutive patients diagnosed as de novo AML were studied by chromosome banding analysis. Among them 32 patients were studied by FISH for the detection of AML1/ETO fusion gene and 11 patients for the detection of CBFbeta/MYH11. Four cases of AML (M2) subtype were positive for t(8;21) and 1 (M4) subtype was positive for inv(16) by karyotyping analysis. When FISH was applied 6 cases all of AML (M2) subtype were positive for t(8;21), 2 of them were of normal karyotype, and 5 cases all of M4EO subtype were found to be positive for inv(16)/ t(16;16) and 4 of them showed normal karyotypes. In conclusion, FISH can be used as a complementary technique to identify t(8;21) and inv16/t(16;16) in de novo AML as these abnormalities are difficult to diagnose in most cases by conventional cytogenetics alone. PMID- 20306686 TI - Prevalence of cytomegalovirus infection among patients undergoing hemodialysis. AB - CMV diseases predominantly occur as an opportunistic infection in patients with severe immunosuppression, such as cancer and renal failure patients, and rarely occur in immunocompetent patients. This study aimed to investigate the prevalence of CMV infection in patients undergoing hemodialysis and to compare the results of different serological tests for CMV infection. Data were collected from 100 patients with renal failure and undergoing hemodialysis in the hemodialysis center of health insurance hospital in Tanta City, Gharbia Governorate, Egypt during the period from January 2007 to January 2008. The data collected from the study patients included sociodemographic characteristics, history of blood transfusion and duration of hemodialysis. CMV/IgG, CMV/IgM and CMV/Ampilcor (PCR) tests were done for each studied patients. Cross-tabulation and Fisher exacts and McNamar's tests as well as concordance agreement tests were used. The mean age of the study patients was 42.0 +/- 8.1 and most of them (60%) were males with the mean duration of dialysis was 1.8 +/- 1.1 years. The seroprevalance of CMV antibodies among these acute patients was 98% using CMV/IgG, 11% using CMV/IgM and 30% by using CMV/Ampilcor (PCR). Comparing these findings showed highly statistically significant difference (P = 0.001). Sensitivity and specificity of CMV/IgG and IgM were varied compared to CMV/Ampilcor test. The IgM was less sensitive (30%) but highly specific (97%), so PCR is the gold standard test with concordance estimated to be 28%. For this test, sensitivity and agreement is increased with decreasing years of dialysis to become 40% and 43%, respectively. On the other hand, however, CMV/IgG appeared to be highly sensitive (93%) and not specific at all (0%), and the agreement with PCR is very low (3%). In summary, the choice of diagnostic IgM and IgG tests depends upon the duration of hemodialysis that might primarily determine the duration of infection, although the use of PCR testing appeared to be more convenient. PMID- 20306687 TI - Saliva as an easy specimen for diagnosis of human and animal fascioliosis. AB - In the present study saliva was evaluated for detection of human and animal fascioliosis. Both saliva and serum samples were collected from 12 Fasciola infected patients, 17 cattles and 20 sheep harboring Fasciola eggs only in their faeces. Samples from negative non-infected hosts were also collected. Experimental infection by F. gigantica in rabbits was carried out for determination of the first time appearance of anti-F. gigantica antibodies (AFAb) and circulating F. gigantica antigen (CFAg). This was carried out by indirect and sandwich ELISA using purified antigen (26-28 KD) and monoclonal antibodies. AFAb were detected in saliva of naturally infected patients, cattles and sheep, the sensitivity of the assays reached 66.6%, 64.7% and 65% respectively, while the sensitivity using serum samples was 91.66, 94.11 & 100% respectively. In the contrary AFAb in saliva was more specific (100%) than that in serum as it was 100%, 92.0% and 96.0% in humans, cattle and sheep respectively. CFAg showed higher sensitivity in diagnosis using saliva in comparison with AFAb as it was 83.3, 76.47 & 85% in patients, cattles & sheep respectively. Similarly, the specificity of CFAg in saliva was higher than that recorded using serum samples as it was 100%, 96.0% and 96.0% in the three groups respectively. AFAb and CFAg were detected in serum of experimentally F. gigntica infected rabbits at the end of the first week post infection, and in saliva at the 15th and 18th day post infection. These data introduce saliva as an easily collected sample that can be used for diagnosis of zoonotic fascioliosis. PMID- 20306688 TI - CD64 cell surface expression on neutrophils for diagnosis of neonatal sepsis. AB - Neonatal sepsis (NS) continues to be one of the most significant causes of neonatal morbidity and mortality. Early identification of Neonatal sepsis is a major diagnostic problem because of the nonspecific clinical signs and limitations of the current diagnostic procedures. Neutrophil CD64 expression has been proposed as a diagnostic test for evaluation of infection and sepsis. We compared the diagnostic utility of neutrophil CD64 expression with IL-6, IL-8, TNFalpha and CRP assays. Peripheral blood samples were taken from 25 neonates classified into two groups; proven NS (n = 15), clinical NS (n = 10) and healthy newborns (n = 10). CD64 expression was analysed by flowcytometry, while serum level of interleukins (IL-6, IL-8), and TNFalpha was determined by ELISA. Expression of CD64 was significantly enhanced in the groups with proven sepsis and clinical NS as compared to the controls (P < 0.05). Similary, TNFalpha, IL-6, IL-8 and CRP levels were significantly elevated in the groups with sepsis and clinical NS as compared to the controls (P < 0.05). Our data indicate that, in addition to serum levels of interleukins (IL-6, IL-8), and TNFalpha, expression of CD64 on neutrophils by flowcytometry could be useful as an indicator of NS due to its early appearance, sensitivity and specificity (96%). In conclusion, neutrophil expression of CD64 is a useful diagnostic tool for early detection of neonatal sepsis. The assay is rapid, easy and reliable. PMID- 20306689 TI - Activation-induced apoptosis in peripheral blood mononuclear cells during hepatosplenic Schistosoma mansoni infections. AB - It is well established that programmed cell death (apoptosis) is an important regulator of host responses during infection with a variety of intra- and extra cellular pathogens. The present work aimed at assessment of in vitro spontaneous and phytohemagglutinin (PHA)-induced apoptosis in mononuclear cells isolated from patients with hepatosplenic form of S. mansoni infections. Cell death data were correlated to the degree of lymphoproliferative responses to PHA as well as to the serum anti-schistosomal antibody titers. A markedly significant increase in PHA-induced apoptosis in lymphocytes isolated from S. mansoni-infected patients was seen when compared to the corresponding healthy controls. However, a slight difference was recorded between the two studied groups regarding the spontaneous apoptosis. This was accompanied with a significant impairment of in vitro PHA induced lymphoproliferation of T cells from S. mansoni patients. Data of the present study supports the hypothesis that activation-induced cell death (AICD) is a potentially contributing factor in T helper (Th) cell regulation during chronic stages of schistosomiasis, which represents a critically determinant factor in the host-parasite interaction and might influence the destiny of parasitic infections either towards establishment of chronic infection or towards host death. PMID- 20306690 TI - Changes of serum growth factors (IGF-I & IGFBP-2) and prediction of response to chemotherapy in patients with acute myeloid leukemia. AB - Insulin-like growth factors (IGFs) and IGF-binding proteins (IGFBPs) possess mitogenic properties promoting cellular proliferation and inhibiting cellular apoptosis. Thus, IGF-system may play a role in tumor proliferation. In the present study, we investigated IGF-I and IGFBP-2 in patients with acute myeloid leukemia (AML) for their predictive value to identify patients who could be responsive to conventional induction chemotherapy. Serum levels of IGF-I and IGFBP-2 were measured (using commercial ELISA kits) in 22 patients with AML. Following treatment, patients were followed up 14 days after the induction cycle to determine if they achieved hematological remission or not. Accordingly, patients were divided into two groups: Responders (10 patients) and Non Responders (12 patients). No significant difference was observed in IGF-1 between Responders and Non-Responders, neither before (79.26 +/- 4.568 pg/ml vs 72.225 +/ 3.62 pg/ml, respectively) nor after induction cycle (74.87 +/- 3.669 pg/ml vs 69.783 +/- 4.329 pg/ml, respectively). However, IGFBP-2 was significantly lower in Responders than in Non-Responders both at diagnosis (4250 +/- 155.099 pg/ml vs 6866.67 +/- 352.122 pg/ml, respectively) as well as after induction cycle of chemotherapy (4130 +/- 324.225 pg/ml vs 7150.00 +/- 265.290 pg/ml, respectively). It is concluded that, serum IGFBP-2 is considered as an independent factor that adds additional information for the prediction of relapse or treatment failure and patients with concentration > or = 4900 pg/ml at diagnosis are suspected to be nonresponders to conventional induction chemotherapy. PMID- 20306691 TI - Leukocytic-vascular endothelial growth factor and integrin alphavbeta3 in acute myeloid leukemia: relation to clinical outcome. AB - Different signaling routes seem to be simultaneously triggered in leukemia, with distinct and overlapping activities. Different reports emphasize the interaction between vascular endothelial growth factor (VEGF) and integrin alphavbeta3 as a key control system of angiogenesis, oncogenesis and metatasis. The current study was undertaken to investigate leukocytic-VEGF and integrin alphavbeta3 as correlated with clinical outcome in patients with acute myeloid leukemia (AML). The study groups included 10 newly diagnosed AML patients before the start of any chemotherapeutic medication and 10 normal healthy control subjects. The level of VEGF was estimated in culture supernatant of peripheral blood mononuclear cells (PBMN) of both groups using commercially available ELISA kit. The degree of integrin alphavbeta3 expression on PBMN was estimated by indirect immunoflourescence. Obtained results showed that the level of VEGF and degree of expression of integrin alphavbeta3 were significantly higher in AML patients than in normal healthy subjects. However, no significant correlation was observed between the levels of VEGF and the degree of expression of integrin alphavbeta3. When clinical findings were concerned, there was a significant positive correlation between VEGF and the percentage of blasts, both in peripheral blood & bone marrow. On the other hand, such correlations were not observed in case of integrin alphavbeta3. In addition no significant correlation was observed between either VEGF or integrin alphavbeta3 and clinical staging, age, and sex. In conclusion, our results proved the importance of VEGF and integrin alphavbeta3 in the pathogenesis of AML. However, the per se increased production or/and secretion of VEGF and integrin alphavbeta3 by leukemic PBMN cells, respectively can not be used as independent predictor (s) for clinical outcome in AML patients. It is more comprehensive to study changes of intracellular signaling pathways when such critically interacting factors are concerned in the leukemic process. PMID- 20306692 TI - New mutations in C1 esterase inhibitor (SERPING1) in a German family with hereditary angioedema. AB - Hereditary angioedema (HAE) is a genetically dominant clinical disorder characterized by recurrent, acute oedema of the skin or mucosa, usually involving the extremities, face, larynx and gastrointestinal tract. C1 inhibitor (C1inh) deficiency is linked to the development of HAE, either by decrease of its plasma level or presence of a dysfunctional protein. The purpose of this study was to identify the genetic abnormality of C1inh in three patients with HAE (mother and her two children). Analysis was carried out using PCR, and direct sequencing of genomic DNA obtained from whole peripheral blood. DNA sequencing of the eight exons of the C1 esterase inhibitor gene (SERPING1) revealed one mutation and one polymorphism in the mother and the two children. The polymorphism was a heterozygous GTG 458 ATG (Val 458 Met) in exon 8 and the mutation was a one nucleotide deletion in codon 456 in Exon 8. This frameshift mutation (CTC456(power)TC) leads to a 45 amino acid larger protein with altered protein sequence and should be regarded as the causative defect in the patients. It is concluded, that heterozygous frameshift mutation at exon 8 alters the protein sequence of the C1 esterase inhibitor, leading to inactive protein in all three patients analyzed. PMID- 20306693 TI - Study of soluble CD44 and its expression by mononuclear cells in children with acute lymphoblastic leukemia: its relation to prognostic factors. AB - To measure sCD44 and its expression in ALL children before and after induction of remission (day 28) and their relation to prognostic factors. Newly diagnosed 30 ALL pediatric patients were examined for sCD44 by ELISA and CD44 expression by flowcytometry and their levels after induction of remission. We correlated them to age, sex, TLC, Hb, platelet count, blast % in PB and BM, Immunophenotyping, and LDH. CD44 expression in ALL patients at the time of diagnosis ranged from 0 - 98% with a mean +/- SD of (41.23 +/- 23.99) and in the control group (range 0 - 11 with a mean +/- SD of 5.5 +/- 6.58), the % of expression was significantly higher in ALL patients than control group (P = 0.001). CD44 expression was significantly decreased by induction of remission (P = 0.001). sCD44 concentration in ALL patients at the time of diagnosis ranged from 105- 449 ng/dl with a mean +/- SD of (246.5 +/- 99.51) and in the control group (range 103 -243 ng/dl with a mean +/- SD of 160.65 +/- 37.12), sCD44 was significantly higher in ALL patients than control group (P = 0.001). sCD44 was significantly decreased after induction of remission (P = 0.001). LDH was elevated in the patients group than the control, (P = 0.001). In conclusion, LDH level at time of ALL diagnosis is an important risk determinant and correlate with degree of anemia, high TLC and high PB absolute blast count. High sCD44 level at the time of diagnosis and rapid decline in its level after treatment suggesting that sCD44 may be a good marker for prognosis and a marker for monitoring response to therapy, a second elevation of sCD44 level after its decline by therapy may suggest ALL relapse. Elevated CD44 expression in ALL patients may mediate lymphoblast metastatic migration. PMID- 20306694 TI - Role of Foxp3 and regulatory CD4+CD25+ T-lymphocytes in bronchial asthma. AB - Regulatory T cells (Tregs) are thought to have a critical role in the suppression of immune responses. In addition to the prevention of the development of autoimmunity, they are thought to have a role in the prevention of allergic responses to environmental allergens. Foxp3 is transcription factor (Foxp3), which is predominantly expressed by CD4+ CD25+ T cells, and may correlates with the suppressive activity of these cells. This study assesses the immunoregulatory role of CD4+CD25+ T-lymphocytes in peripheral blood of asthmatic children and possible role of Foxp3 mRNA expression. The study included thirty children, 10 with acute asthmatic exacerbation, 10 during rest state with no asthma manifestation and 10 apparently healthy children. T-regs, and Foxp3 mRNA were investigated using Flowcytometry and RT-PCR respectively. Early morning sputum was also collected for determination of eosinophillia. Significant increase in the percent of CD4+CD25+ was found in acute asthmatic as compared to stable asthmatic cases (23.3 +/- 3.74% vs 13.97% +/- 1.18%), and in acute asthmatic group than control group (13.97% +/- 1.18% vs 8.12 +/- 1.65%), (P < 0.001). Similarly, significant increase in Foxp3 mRNA expression was found in acute asthmatic cases as compared to stable and control children (P < 0.001). A significant positive correlation was found between Foxp3 mRNA expression and the percent of CD4+CD25+ T cells in all studied groups (r = 0.91 P = 0.01). It is concluded that regulatory CD4+CD25+ T-cells may play a critical role in maintaining suppression and protection against allergic bronchial asthma and that Foxp3 may be important in the development of these cells. PMID- 20306695 TI - Gene deletion of glutathione S-transferase M1 and T1 and risk factors of hepatocellular carcinoma in Egyptian patients. AB - Genetic polymorphic forms of glutathione-S-transferase (GST) were found to be associated with risk for various malignancies. The present study was undertaken to evaluate the risks-associated with GSTT1 and GSTM1 gene polymorphisms and hepatitis virus-related hepatocellular carcinoma (HCC) in an Egyptian population. Sixty patients diagnosed with HCC were subdivided into 3 groups: group I, 31 patients with HCC and HCV-related cirrhosis; group II, 19 patients with HCC and HBV- related cirrhosis and group III, 10 patients with HCC and cirrhosis of non viral aetiology. Fifty cirrhotic patients without HCC were also included as a control group. Patients and controls were subjected to thorough history taking and clinical examination, liver function tests, hepatitis viral markers, anti Bilharzial antibodies and serum alpha fetoprotein levels. Rectal snip for the diagnosis of active Bilharziasis, abdominal ultra-sonography and CT abdomen were performed for patients as well as liver biopsy when indicated. GSTM1 and GSTT1 were tested in peripheral blood mononuclear cells by PCR. GSTM1 gene deletion (null genotype) was observed in 56.7% of HCC patients and in 38% of the control group (P < 0.05). The GSTT1 null genotype was detected in 41.7% of the HCC patients compared to 22% of control patients (P < 0.05). The double genes null of GSTM1 and GSTT1 was detected in 10% of all HCC patients and in 2% of the control cases (P < 0.05). Comparison between the subgroups of HCC revealed that the GSTM1 null genotype was detected in 67.7% of group I, 47.4% of group II and 40% of group III cases, with a significant increase in group I compared to other HCC subgroups (P < 0.001). In addition, the GSTT1 null gene was observed in 35.5% of group I, 57.9% of group II, and 30% of group III, with a significant increase in group II (P < 0.01). In conclusion, our findings suggest that GSTM1 and GSTT1 polymorphisms appear to be associated with a modest increase in the risk of HCC in Egyptian patients. Studies with a larger sample size are still required to confirm the results and to explore the association with risk factors other than HCV and HBV in this population. PMID- 20306696 TI - Flowcytometric study of expression of perforin and CD134 in patients with systemic lupus erythematosus. AB - Perforin is a membrane-disrupting protein that allows the entry of granzymes into a target cell inducing degradation of target substances in the cytoplasm and nucleus thus leading to programmed cell death or apoptosis. CD134 was originally described as an activation antigen found on activated T cells. In this work Flowcytometry was used to evaluate the expression of perforin and CD134, as a costimulatory molecule on T cells, in patients with Systemic Lupus Erythematosus (SLE) to elucidate their role in the pathogenesis of SLE and disease severity. The study was conducted on 15 patients with SLE, 6 patients out of the 15 patients were suffering from lupus nephritis, 10 healthy subjects were included as controls. The results revealed that absolute number of circulating CD3+ lymphocytes in the patients was significantly lower than the controls (P = 0.013). The percentage of CD8+ CD3+ T cells was significantly increased in the SLE group when compared to that of CD4+ CD3+ T cells in same group (P = 0.001) Perforin expression on both CD4+ and CD8+ cells was significantly increased in patients compared to controls. (P = 0.002 & P = 0.001, respectively). In addition, a significant increase was observed in the percent of pf+CD8+CD3+ in the patient group compared to that of pf+CD4+CD3+ in the same group (P = 0.001). There was a significant increase in the expression of CD134 on CD4+ and CD8+ cells (P = 0.001 & P = 0.001 respectively). Also, in the same group of patients a significant increase was detected in the frequency of CD134+CD4+CD3+ T cells compared to that of CD134+CD8+CD3+ T cells (P = 0.032). A significant positive correlation was detected in the patient group between CD134 and perforin expression on both CD4+ and CD8+ T cells (p = 0.045, r = 0.523). Moreover, CD134+CD4+CD3+ was also correlated positively with urinary proteinuria (P = 0.023, r = 0.524). Our data suggest the role of Perforin + cytotoxic T lymphocytes and CD134+ cells in the pathogenesis of autoimmunity of SLE. Thus, inhibition of perforin could be beneficial for SLE patients. Targeting pf and CD134 could be a new therapeutic approach in patients with SLE. PMID- 20306697 TI - Significance of immunoregulatory T cells in different stages of breast cancer patients. AB - Evidence from breast cancer patients suggests that increased T suppressor cells activity may be associated with poor immune responses to tumor antigens and contribute to immune dysfunction. It was demonstrated that these suppressor cells could be CD4+CD25+ T regulatory cells (Treg cells). FOXP3, a forkhead/winged helix transcription factor was found to be essential for the development and control of Tregs. It has been used recently as a biomarker and a prognostic factor for malignant human tumors. The aim of this study was to evaluate the significance of CD4+CD25+ Treg cells changes in the peripheral blood in relation to FOXP3 expression in different stages of breast cancer patients. The present study included 30 female patients of breast cancer (group A) and 10 female healthy volunteers as control (group B). In group A, ten patients (33.3%) were in stage I, ten patients in stage II (33.3%) and ten patients in stage III-IV (33.3%). Serum level of tumour marker (CA15-3) was measured by ELISA. Determination of the percent expression of CD4+ CD25+ of total CD4+ T cells and FOXP3+ Treg cells was done by flowcytometry. The serum level of CA15-3 was significantly higher in group (A) than in group (B) (P = 0.001). Also, CA15-3 was significantly increased as the stage of the disease increased. The percentages of both CD4+ CD25+ and FOXP3+ Tregs in the peripheral blood were significantly higher in group (A) than in group (B) (P = 0.001) and they increased significantly as the stage of the disease increased. A significant positive correlation was found between the percentage of CD4+ CD25+ Tregs and FOXP3+ Tregs in the peripheral blood (P = 0.0649, r = 0.001) and with serum level of CA15-3 (P = 0.880, r = 0.001). It was concluded that CD4+CD25+ FOXP3+Tregs may be responsible for immune suppression in breast cancer. They are also valuable for assessing disease prognosis. This finding can be of utmost significance under the light of Tregs being implicated in carcinogenesis and ongoing efforts towards the development of anticancer approaches specifically inhibiting the expression and/or function of Foxp3 by tumor-associated Tregs. PMID- 20306698 TI - T - helper2 /T - helper1 imbalance in respiratory syncytial virus bronchiolitis in relation to disease severity and outcome. AB - The present study included 80 Egyptians infants with acute bronchiolitis; age ranged from 2 to 22 month and consisted of 60 males and 20 females. In addition, 30 apparently healthy infants of matched age and sex were also included as controls. Besides taking history, thorough clinical examination and routine laboratorial investigations, arterial oxygen saturation, RSV tissue culture of nasopharyngeal lavage, indirect immnoflourescence for serum IgM against RSV, serum IL-4 and IFN-gamma were done. Results obtained showed that viral bronchiolitis is predominant in male around 6 month of age and in winter months. RSV was identified in 72.5% of cases. Level of serum IL-4 was significantly higher in RSV positive patients than either RSV negative patients or controls (P < 0.001). Furthermore, in RSV positive patients, IL-4 level was significantly higher in severe and fatal cases than in milder and surviving cases (P < 0.001). Serum IFN-gamma showed no significant difference between RSV positive and RSV negative patients in RSV positive cases it was significantly lower in more severe and fatal cases than milder and living ones (P < 0.05). The ratio IL-4/ IFN-gamma was significantly higher in RSV positive than RSV negative and controls (P < 0.001 and P < 0.05 respectively). Absolute eosinophilic count (AEC) and percent of oxygen saturation (SaO2%) showed significantly lower values in RSV positive patients than RSV negative (P < 0.001), but the latter showed significantly higher AEC than controls (P < 0.05). In RSV positive group, both parameters were significantly lower in more severe and fatal cases than milder and living ones (P < 0.001). In RSV positive group, significant positive correlations were found between disease severity and either serum IL-4 or IL-4 /IFN-gamma ratio (r = 0.789 and r = 0.823, P < 0.001 respectively) but disease severity was inversely correlated with either AEC or SaO2 % (r = -0.962 and r = -0.828, P < 0.001 respectively). RSV was identified as the major etiologic virus of bronchiolitis in young infants. Viral tissue cultures and indirect immunoflourescene are of equally diagnostic value but both may be needed. Most of the severe and fatal cases are in RSV positive group. Th2/Th1 imbalance reflected on IL-4/IFN-gamma ratio is more deranged in RSV bronchiolitis with Th2 predominance especially in more severe and fatal cases. These conclusions may be a rationale for the implementation of antiviral drugs in severe cases of bronchiolitis, however, further studies are needed to demonstrate the effect of antiviral drugs on cytokines levels during therapy. PMID- 20306699 TI - C-Phycocyanin inhibits cell proliferation and may induce apoptosis in human HepG2 cells. AB - C-Phycocyanin (C-Pc) is one of the major biliprotein pigments of unicellular cyanbacterium of Spirulina platenesis, it has nutritional, medicinal, and hepatoprotectant application. The growth and multiplication of human hepatoma cell lines (HepG2) under the effect of different concentrations of C-PC (0.8, 1.75, 3.5 and 7.0 microg/ml) against untreated cells as control for 24h were investigated. The results showed that the proliferating cells in presence of C-PC reached 70, 51, 44, and 39%, respectively. The results revealed that the greatest reduction in proliferation of cells was recorded at 7.0 microg/ml and LC50 at 1.75 microg/ml of C-PC. In parallel, to the previous results HCl-denatured MG-P revealed that in mass of cells there is a pattern of apoptosis because the expanded cytoplasmic area (bluish-green) reduced and appeared faintly red as C-PC concentration increased. Moreover, the cells lost all the nuclear entities then, become fragmented and having no nuclear remnants. The C-PC may be a new potential anti-cancer drug for therapy of human hepatoma cells. PMID- 20306700 TI - The anti-tumor effect of bee honey in Ehrlich ascite tumor model of mice is coincided with stimulation of the immune cells. AB - Honey is thought to exhibit a broad spectrum of therapeutic properties including antibacterial, antifungal, cytostatic and anti-inflammatory activity and has been used for the treatment of gastric ulcers, burns, and for storage of skin grafts. The present study investigated the antitumor effect of bee honey against Ehrlich ascites tumor in mice and the possible mode of antitumor action. Peroral administration of mice with honey (10, 100 or 1000 mg/ 100 g BW) every other day for 4 weeks before intraperitoneal inoculation with Ehrlich ascites tumor (EAT, 1 x 10(6) cells) increased the number bone marrow cells as well as peritoneal macrophages, but not peripheral blood leukocytes nor splenocytes. The phagocytic function of macrophages as well as the T- and B-cell functions were also increased. Honey pre-treatment also recovered the total lipids, total proteins, as well as liver and kidney enzyme activities in EAT-bearing mice. In vitro studies on EAT cells demonstrated inhibitory effect of honey on tumor cell proliferation, viability % of tumor cells as well as the size of solid tumor. The present results indicate that the preventive treatment with honey is considerably effective against EAT in mice both in vivo and in vitro. The antitumor activity of honey may occur through the activation of macrophages, T-cells and B-cells. PMID- 20306701 TI - [Exploratory studies on genetic biomarkers related to serious drug adverse reactions]. AB - Serious adverse events (SAEs) induced by drugs occur rarely, but the symptoms are very critical and generally not related to their pharmacological activities. Although SAEs should be avoided wherever possible, their occurrence is unpredictable at this time. In this article, we describe the clinical condition, figures on reported occurrence in Japan and studies on genetic markers related to serious cutaneous adverse reactions (SCARs), drug induced liver injury (DILI and rhabdomyolysis among SAEs. Then we introduce our last 3 years' approach of exploratory study on genetic markers for Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN), two of SCARs, useful for Japanese patients, including construction of a new case collection system, study methodology and progress. As the result at this moment, no Japanese SJS/TEN patients including 12 carbamazepine-related and 23 aromatic anti-epileptic agent-related ones carried HLA-B 1502 that was reported to have a strong association with carbamazepine induced SJS/TEN in Han Chinese patients. On the other hand, 5 in 15 allopurinol related SJS/TEN patients were found to have HLA-B 5801 that was detected as a genetic marker for allopurinol-induced SCARs in Han Chinese and Caucasians. Hereafter, we have a plan to begin the new exploratory studies on genetic markers for DILI and rhabdomyolysis, in addition to SJS/TEN patients. PMID- 20306702 TI - [Research strategy for evaluation methods of the manufactured nanomaterials in NIHS and importance of the chronic health effects studies]. AB - Manufactured nanomaterials are one of the most important substances for the nanotechnology. The nanomaterials possess different physicochemical properties from bulk materials. The new properties may lead to novel biological effects and also may or may not cause unknown adverse effects. However, the toxicological evidences are very limited, and there are no standardized evaluation methods at present. Some domestic and international activities are ongoing, in order to share the information or to standardize the methods. In 2005, our institute launched the research on the establishment of health risk assessment methodology of manufactured nanomaterials by funding from the research grants of the Japanese Ministry of Health, Labour and Welfare. The project contains four themes. The first is development of measurement methods of nanomaterials from biological samples. The second is development of dispersion methods in in vitro systems. The third is development of inhalation exposure systems. And the last is development of in vivo systems for evaluating long-term health effects. As evaluation materials, fullerene, titanium oxide and multi-walled carbon nanotubes were chosen because of their high production volumes. In the course of the research project, we revealed that the nanomaterials were competent to cause chronic effects, by analyzing intraperitoneal administration studies and carcinogenic promotion studies. These studies suggested that even aggregated nanomaterials were crumbled into nano-sized particles inside the body during the long-term, and the particles were transferred to other organs. Additionally, long lasting particles/fibers in the particular tissues may cause chronic adverse effects. The phsyco-chemical properties or toxicity mechanism related with these chronic effects were considered to be different from those properties or mechanism related to acute toxicity. Therefore, we suggested that the toxicological characterization of chronic effects by nanomaterials would be important for the future research. Also, investigations of the toxicokinetic properties and biological interaction with nanomaterials are important to predict the chronically targeted tissues after exposure. PMID- 20306703 TI - [Characterization of anti-mouse prion peptide single chain Fv antibody by phage display]. AB - Antibodies can distinguish not only differences in amino acid sequences (primary structure), but also differences in three-dimensional structure and thus may be useful for detecting the conversion of prion proteins, especially in vivo. For diagnosis, we prepared chicken single chain variable fragment (scFv) antibodies that specifically recognized a prion protein using a phage display approach. As antigen, mouse prion protein (MoPrP) 138-153 containing YYR residues was conjugated with KLH. Total RNA was extracted from the splenocytes of an immunized chicken, and the cDNA of scFv was ligated in a phagemid vector. The phage display scFv library was panned against the peptide antigen four times. Twenty-three scFv phage clones that tested positive using ELISA with the peptide antigen were then reacted with recombinant mouse prion protein (23-231), mouse brain homogenate, mouse neuroblastoma Neuro-2a, recombinant human V129 and M129 prion proteins, and human glyoma T98G using ELISA, immunoblotting analysis, and immunocytochemistry. The results suggested that the scFv phage clones were useful for detecting mouse and human prion proteins. PMID- 20306704 TI - [Histamine food poisonings in Japan and other countries]. AB - Histamine food poisonings are allergy-like food poisonings caused by the ingestion of spoiled fish containing markedly elevated histamine levels. We examined histamine food poisonings in Japan from 1998 to 2008. In average 8 food poisonings and 150 cases were reported annually and there was no fatality case. In more than 80% of remaining food samples, histamine content exceeded 20 mg/100 g. These poisonings were caused by tuna, billfish (marlin) and mackerel, which contained higher level of histamine than other fishes in histamine food poisonings in Japan. Cooking methods of these fishes were mainly "broiled". We also studied histamine food poisonings in other countries. Tuna was the main fish in histamine food poisonings reported to Centers for the Disease Control and Prevention (CDC) in the US and Ozfoodnet in Australia from 2000 to 2006. In the US, histamine food poisonings were also caused by mahimahi and escolar fish. Our review will be useful for in taking measures to reduce risk of histamine food poisonings. PMID- 20306705 TI - [Cytotoxicity of fullerene (60), carbon nanotube, and their derivatives in V79 cells and cultured normal human astrocytes]. AB - Fullerenes are a family of carbon allotropes, molecules composed entirely of carbon. Fullerenes have been developed in various forms and functions and are expected to be used for novel medical materials targeting on brain. Information on cytotoxicity of fullerenes on brain function, however, is few; thus we examined the effect of fullerenes on the brain astrocytes in this study. We used fullerene [60], hydroxylated-fullerene [60], carboxylated-fullerene [60], dimalonilated-fullerene [60], carboxylated-carbon nanotube and amino-carbon nanotube. At first, we examined cytotoxicity of fullerenes by V79 colony assay. Fullerenes inhibited the cell growth in a concentration-dependent manner, but 50 percent growth inhibition concentrations were different among fullerene derivatives, which we used. Cytotoxicity of carbon nanotubes was stronger than that of fullerenes. Secondly, we performed the microtiter tetrazolium assay of normal human astrocytes and measured the effects of fullerenes on cell activity. Fullerenes and carbon nanotubes decreased mitochondrial activity. In addition to this, it was observed that fullerenes and nanotubes adhered to cells. These results suggest that fullerenes and carbon nanotubes have cytotoxicity and the effects are different from each other due to their side chain and steric forms. We expected that fullerenes and carbon nanotubes gave physical stress to cells and caused cytotoxicity. In conclusion, it was suggested that safety evaluation is needed for fullerenes and carbon nanotubes individually. PMID- 20306706 TI - [Major revision of the allergen database for food safety (ADFS) and validation of the motif-based allergenicity prediction tool]. AB - We have been maintaining an integral web server system, the Allergen Database for Food Safety (ADFS), since 2005 (http://allergen.nihs.go.jp/ADFS/). Recently, a group at the University of Nebraska-Lincoln released a new version of an allergen database, AllergenOnline. This database includes more than 1,300 allergens, all of which have been peer-reviewed by an international board of allergology experts. Here, we have totally revised the dataset of the ADFS by comparing it with that of AllergenOnline to improve the reliability of our allergen data. Moreover, the performance of our web-based tool for predicting new allergens (motif-based method), which was developed according to a theory proposed by Stadler & Stadler (2003), was validated using three methods. As a result of the integration of this allergen data, the number of (iso)allergens in the ADFS has increased to 1340, and epitope information is now available for 76 allergens. Using model datasets, the precision, recall, and specificity of our motif-based allergenicity prediction tool was proved to be 100.0%, 99.4%, and 100.0%, respectively. These results were similar to those for the original motif-based prediction model that was previously reported and are much better than those of the method recommended by FAO/WHO, especially with regard to the precision of predictions. PMID- 20306707 TI - [Detection of the preservative chlorphenesin in cosmetics by high-performance liquid chromatography]. AB - A simple determination method for preservative chlorphenesin in cosmetics was developed. Cosmetic samples were dissolved in methanol. The sample solution was analyzed by high-performance liquid chromatography (HPLC) with ODS column, using water-methanol (55:45) or water-acetonitrile (3:1) adjusted to pH 2.5 with phosphoric acid as the mobile phase. Chlorphenesin was detected with ultraviolet light detection at 280 nm. A linear relation was obtained between the peak areas and the concentrations of chlorphenesin in the range of 1-500 microg/ml. The determination limit of chlorphenesin was 1-2 microg/ml. Recoveries of chlorphenesin spiked in lotion and milky lotion at the levels of 0.03% and 0.3% were 98.8-100.0%. This method was applied for cosmetics including 0.03% and 0.3% of chlorphenesin and their content corresponded with the determined values. PMID- 20306708 TI - [Detection of clobetasol propionate in a cream advertised to be effective against atopic dermatitis]. AB - Addition of medical ingredients to cosmetics is prohibited. However, last year some cases of illegal cosmetics containing steroids were successfully identified. We have already reported an analytical method to detect steroids in cosmetics [Bull. Natl. Inst. Health Sci, 126, 51-56 (2008)]. In this study, we initially examined whether this method could be applied for the detection of some new steroids as target chemicals. We then used this developed method to detect steroids in cosmetics obtained from manufacturers by spot checks. These manufacturers have been advertising the effectiveness of a steroid-free cream against atopic dermatitis. The results revealed that clobetasol propionate (CP) was present in this facial moisturizing cream, which was available in the market. The steroid was extracted with methanol. After ultrasonication and centrifugation, the resulting supernatant was injected into the high-performance liquid chromatography system equipped with an ODS column. The separation was achieved using a mixture of acetonitrile and water as the mobile phase. The retention times of the observed peaks were in accordance with those of some preservatives and CP. The presence of CP was also confirmed by thin-layer chromatography. The concentration of CP in the cream was approximately 0.039%. CP is a steroid that has the strongest effect as compared to those of other steroids. The cream was therefore recalled for safety reasons. PMID- 20306709 TI - [Studies on an analytic method for detection of prohibited ingredient, strontium dichloride in cosmetics]. AB - Strontium dichloride is one of the prohibited ingredients in cosmetics due to the Japanese Pharmaceutical Affairs Act. We established the analytical method for strontium dichloride in cosmetics by capillary electrophoresis (CE). The toothpaste was dispersed into water. After ultrasonication for 10 min, the solution was centrifuged at 3000 rpm for 10 min. The supernatant was filtrated through a membrane (0.45 microm), diluted 100-times with water, and injected into CE. The calibration curve showed linear between the concentrations of strontium dichloride (from 2 to 50 microg/ml) and the peak area of strontium ion. Detection limit of strontium dichloride is 2 microg/ml. There was no interference of the ingredients in the toothpaste. PMID- 20306710 TI - [Development of a liquid chromatography-tandem mass spectrometry method for the determination of fullerenes C60 and C70 in biological samples]. AB - Wide application of fullerenes in various areas would increase the risk of occupational and environmental exposure to human. However, information about toxicity and biological behavior of fullerenes is not sufficient for the risk assessment at present. For the determination of fullerene C60 in biological samples, an analytical method using high performance liquid chromatography- tandem mass spectrometry (LC-MS/MS) and extraction procedure from tissues of experimental animals was established in this study. Using LC-MS/MS with an atmospheric pressure chemical ionization in negative mode, C60 were identified and quantified. After optimization of mobile phase and separation column, good separation of peak of fullerene and sensitivity were obtained in case of using toluene and acetonitrile as the mobile phases and Develosil RPFULLERENE as the separation column. For method validation, rat brain, kidney, liver, lung, spleen tissues and blood were used for recovery tests. Good results were obtained and the recovery percentages were found to be between 98.1% and 106.5%. PMID- 20306712 TI - [Literature survey of Salmonella contamination in eggs and egg products in the world]. AB - Salmonella species are common bacterial pathogens associated with human gastroenteritis worldwide. In Japan, salmonellosis is one of the main food-borne bacterial illnesses and, especially, Salmonella Enteritidis infections have been strongly associated with the consumption of eggs and egg-containing foods. In this study, we performed the literature survey of Salmonella contamination in shell eggs and liquid eggs worldwide for comparing the prevalence among the countries and summarized in the tables. This survey clarified that one out of several thousands of retail shell eggs were contaminated with Salmonella spp. in Japan and the prevalence of Salmonella in retail shell eggs were higher in some countries. This paper is useful for providing referable data on Salmonella contamination in shell eggs and liquid eggs in Japan, especially for researchers of other countries. PMID- 20306711 TI - [Serious product accidents due to the chemical substances used in household products in fiscal years 2007 and 2008]. AB - The revised consumer product safety law was enforced in 2007. Then, the collection and publication system of the information of product accidents was newly included. Serious product accidents due to the chemical substances used in household products had 32 cases in fiscal years 2007 and 2008. These household products were a desk mat, a sectional bed, a spray-type adhesive, a paint and an adhesive for table tennis rackets. The safety measure of the household product was explained based on the law for the control of household products containing harmful substances. PMID- 20306713 TI - [Studies on the results of monitoring of veterinary drug residues in food products of animal origin in Japan and other countries]. AB - The positive list system was introduced in Japan for agricultural chemicals such as pesticides, feed additives and veterinary drugs in May 2006. After this time, food containing residues of these chemicals exceeding MRLs, or the default tolerance (uniform limit: 0.01 ppm) cannot be marketed in Japan. The number of chemicals to be tested for imported food at the port increased remarkably. We studied on the results of monitoring of imported food for the residues of veterinary drugs and change in trend of violation after the enforcement of the system. The number of violation of the veterinary drugs in imported food increased largely, most of them were attributed to chloramphenicol and nitrofurans in seafood from Asian countries. Monitoring of the veterinary drugs in seafood in other countries such as EU, United States, United Kingdom and Australia were also studied. PMID- 20306714 TI - [Evaluation of functional interaction of pharmaceuticals and chemicals with factors determining growth, development or differentiation]. PMID- 20306715 TI - [Chagas disease: re-emergent or neglected]. AB - Chagas disease is a tropical parasitic disease distributed throughout America, from southern United States to Argentina, mostly, in poor and rural areas of Central and South America. According to the latest estimates, there are 8 million people all over the world infected by the parasite and in 2008, 11000 deaths were registered. Currently, with the occurrence of internal migrations from rural areas to cities, the disease is changing the establishment of its epidemiological profile. Instead of an effective control or eradication, as consequences of the antichagasic campaign initiated in Venezuela 47 years ago, as many cases are emerging today, in some westerns states of the country, as those reported at the beginning of the last century. In addition, there is a considerable increase in the oral transmission of the disease, through neglect and the lack of sanitary controls in food processing. For these reasons, a monitoring system of rapid response must be implemented by the Venezuelan health system to control the disease. PMID- 20306716 TI - [Characterization of extended-spectrum beta-lactamases in nosocomial strains of Klebsiella pneumoniae]. AB - In this study, 25 strains of K. pneumoniae, isolated from patients with nosocomial infections from August 2002 to December 2003, were examined to determine their antimicrobial susceptibility, plasmid profile, transfer capacity of resistance determinants and bla(TEM), bla(SHV), and bla(CTX-M) genes. Nineteen nosocomial strains revealed a weakened susceptibility to third-generation cephalosporins and aztreonam, and were extended-spectrum beta-lactamases (ESBLs) producers. All strains presented conjugable plasmids with a conjugation frequency of 10(-3) to 10(-4) transconjugants/donor cell. The analysis of restriction patterns revealed the presence of three differents plasmids. The Escherichia coli transconjugants were ESBLs producers and expressed resistance for aminoglucosides and chloramphenicol. The bla(TEM) gen was found in all transferables plasmids and the bla(SHV) and bla(CTX) genes were found in transferables and no transferables plasmids. The enzymes identified in the isolates were TEM-1 SHV-5-2a and CTX-M-2. The plasmids present in the K. pneumoniae strains play an important role in the dissemination of the genes encoding resistance to beta-lactams and other antimicrobial agents. PMID- 20306717 TI - [Osmolality of products and formulas for nutritional therapy]. AB - The objective was to determine the osmolality of products and formulas for nutritional therapy available in Venezuela. The samples were grouped as follows: infant formulas, premature infant, follow up, 1 to 4 years, soy based, lactose free, anti-reflux, hypoallergenic, complete beverages, polymeric formulas, semi elemental, caloric and protein modules. A vapor pressure digital osmometer was used, analyzing five samples of each product from different lots, prepared by weigth or with scoop. When the variation coefficient of the osmolality measurements was higher than 10%, five additional samples were analyzed. Averages, standard deviation, and the variation coefficient of the osmolality measures (95% reliability) were calculated. The osmolality (mmol/kg) of infant and premature infant formulas were between 258 and 309; follow up formulas ranged between 256-390; 1 to 4 years: 343-399; soy based: 155-252; lactose free: 163 248; anti-reflux: 230-292; hypoallergenic: 220-335; complete beverages: 205-454; polymeric formulas: 247-588; semi-elemental: 238-289; caloric module: 89-99 and protein module: 30-60. We found that almost all the formulas prepared with scoop had higher osmolality and variability than the same products prepared by weight. Some follow up, polymeric, 1 to 4 years formulas and complete beverages had high osmolalities and therefore should not be administered to infants, and must be administered with caution to children and adolescents when the gastrointestinal tract is compromised. PMID- 20306718 TI - Human papillomavirus false positive cytological diagnosis in low grade squamous intraepithelial lesion. AB - The purpose of this study was to investigate the number of Human Papillomavirus false positive cytological diagnosis in low grade squamous intraepithelial lesions (LSIL). Three hundred and two women who assisted to an Out-Patient Gynecologic Clinic in Maracaibo, Venezuela, were recruited for this study. Each patient had the Pap smear and a cervical swab for Hybrid Capture 2 (HC2). Three cytotechnologists reviewed the Pap smears and two pathologists rescreened all of them. The cytotechnologists reported 161 (53.3%) Pap smears negatives for intraepithelial lesion (IL) or malignancy, and 141 cases (46.7%) with epithelial abnormalities. They reported 46% of 302 patients with HPV infection in Pap smear slides. The pathologists found that 241 (79.8%) Pap smears were negatives for IL or malignancy and 61 (20.2%), with abnormal Pap smears. They found 14.6% HPV infection in all Pap smears (p<0.0001; 46% vs 14.6%). The HC2 study showed that 47 samples (15.6%) were positive for HPV. The study found that 114 Pap smears (False Positive: 85%) of 134 reported by the cytotechnologists and 24 (False Positive: 43%) of 56 cytologies reported by the pathologists as LSIL, were negative for HPV infection determined by HC2 (p<0.00003). The present study suggests that the cytotechnologists overdiagnosed cellular changes associated with HPV infection in the Pap smear, increasing the FP cytological diagnosis of LSIL. PMID- 20306719 TI - [Malaria and pregnancy. San Isidro parish, municipality Sifontes, state of Bolivar, Venezuela, 2005-2006]. AB - Malaria in pregnancy constitutes a world-wide public health problem. With the objective of studying malaria in pregnancy, a cross-sectional, descriptive epidemiological study was carried out on 449 women, in mining areas of the San Isidro parish, municipality Sifontes, state of Bolivar, Venezuela, during 2005 2006. The Malaria incidence in pregnant women was 27.4%: 87% for Plasmodium vivax, 12.2% Plasmodium falciparum and 0.8% mixed infections. These infections appeared mainly during the second trimester (41.5%). Of the women studied, 71.5% presented symptoms and 26.2% had anemia. A higher proportion of abortions occurred among infected mothers with Plasmodium vivax (3/5); and there were 3.3% low-birth-weight neonates. A case of placental malaria (0.8%) for Plasmodium vivax was registered. An association was observed between mothers receiving chemoprophylaxis and the adequate weight of newborns (chi2 = 41 23gl. p < 0.0001), independently of the regularity of treatment. It is concluded that the routine administration of antimalarial quimioprophilaxis against P. vivax to pregnant women, could be justified in endemic areas. It is advisable to establish the routine diagnosis and opportune treatment during the prenatal practice in the transmission areas of malaria. PMID- 20306720 TI - [Effects of prenatal exposure to paraquat on the development of amino acid synaptic transmission in mouse cerebral parietal cortex]. AB - The effects of prenatal expossure to paraquat (PQ) were studied on postnatal development of mouse parietal cerebral cortex, in particular, the ontogenesis of amino acid synaptic transmission. Pregnant NMRI mice were separated into two groups: the experimental group received 5 doses of 10 mg PQ/kg body weight, between days of gestation (G)12 and G20, whereas the control group received physiological saline solution. Levels of neurotransmitter amino acids: Asp, Glu, Gly, GABA and Tau were determined by HPLC between postnatal (P) days P1 and P30. Between P3 and P15, a significant increment in the levels of excitatory amino acids, Asp and Glu, were observed in mice exposed to PQ, as compared with the control group. With respect to the inhibitory neurotransmitter levels, in the group exposed to PQ, the more important changes were observed in Gly between P1 and P15. In relation to taurine, its levels remained significantly higher between P1 and P7 with respect to the control group. It is important to emphasize that at P30, the levels of all neurotransmitters in the experimental group were significantly lower than those of control. In conclusion, prenatal exposure to PQ caused neurotoxicity in the developing mouse parietal cortex, as shown by the alterations in the basal levels of amino acid neurotransmitters, with the excitatory predominating over inhibitory neurotransmission, throughout the studied developmental period. These alterations could indicate the occurrence of important cortical injuries, such as decrement in some neuronal populations, inadequate formation of intrinsic cortical circuits and alterations in synaptogenic processes. PMID- 20306721 TI - [Interaction between gabapentin and D-serin in the formalin orofacial test]. AB - Gabapentin is a useful agent for the relief of trigeminal neuralgia and orofacial phantom pain. However, there is scarce information on the gabapentin analgesic effect in orofacial pain models. We tested the analgesic action of gabapentin on the formalin-induced face grooming in the rat, an orofacial pain paradigm. IP Gabapentin (10 mg/kg), induced a drastic reduction in face grooming during phase I and II, indicating a clear-cut antinociceptive effect. However, at 1 mg/kg, gabapentin had an analgesic effect only on phase I. D-serine (100 microg, ICV) was silent when given alone and did not antagonize the antinociceptive effect of gabapentin. On the contrary, gabapentin 1 mg/kg plus D-serine significantly reduced face grooming in phase II. These results show a difference between gabapentin induced orofacial analgesia and previous studies showing gabapentin induced hind paw analgesia in the formalin test, only during phase II, as well as D-serine antagonism of gabapentin. The results are discussed in terms of different pain processing of hind paw, versus orofacial nociceptive stimulation. PMID- 20306722 TI - Relationship between placental alkaline phosphatase activity and cord blood glucose, albumin and neonatal birth weight at term. AB - It has been observed that placental alkaline phosphatase (PAP) activity progressively rises as pregnancy advances, possibly, because of its increasing synthesis by placental tissue. The present investigation therefore, examines the relationship between placental alkaline phosphatase activity and the biochemical indices of foetal nutrition (cord blood glucose, albumin) and growth (neonatal birth weight). Placental and umbilical cord blood samples were collected from one hundred and five deliveries and prepared for both, placental alkaline phosphatase assay, and glucose and albumin estimations using standard procedures. The birth weights of the neonates at term were taken and recorded. Correlation analyses of the data obtained show significant positive relationships between PAP and cord blood glucose (r2 = 0.86, p<0.05), albumin (r2 = 0.71, p<0.05) and birth weight (r2 = 0.68, p<0.05), but no significant relationship with gestational age. PAP may be essential in nutrient mobilization to the foetus. However, further studies involving more subjects and an intrauterine growth retardation control group (IUGR) are required to fully document the present report. PMID- 20306723 TI - [Human fasciolosis in Mara municipality, Zulia state. Venezuela: prevalence and asociated factors]. AB - In Venezuela, human Fasciolosis shows a low frequency. However, Mara Municipality is a highly endemic region for bovine fasciolosis and there are no reports of this parasite infection in humans. To determine the prevalence and associated factors to human fasciolosis in Mara municipality - Zulia state, a total of 51 blood and stool samples were collected. Serums were tested by ELISA and Western Blot (WB) assays, with excretion-secretion antigens of Fasciola hepatica (AFhES). The serum samples that resulted positive by these assays were tested by ELISA IgG anti Toxocara sp, Toxoplasma gondii and cysticerosis. Stool samples were concentrated by the Ritchie and rapid sedimentation techniques. Two serum samples were reactive to ELISA AFhES (3.9%) and these did not recognize the specific molecules of WB-AFhES detected by serum from patients with an absolutely demonstrated infection. Both participants were not positive to IgG anti Toxocara sp, Toxoplasma gondii, cysticerosis, and stool samples of these were negative to intestinal parasites. The general prevalence of intestinal parasites was 52.9% (27/51), being protozoa more frequent than helminthes. No Fasciola eggs were found. The two positives participants had in common that both had worked as fresh pasture cutters. These results suggest that the population had been in contact with F. hepatica, with no active infection because of the lack of specific molecules recognition and the absence of eggs in stool samples. Human fasciolosis has a low frequency in Venezuela and is underestimated and underrecognized by health workers and the general population. PMID- 20306724 TI - [Bilateral gonadectomy and laparoscopic hysterosalpingectomy in an adolescent with ovotesticular disorder of sexual development]. AB - Disorders of sexual development in adolescents refer to children whose genitals at birth present characteristics of both genders, or to those children with normal phenotype that present a development alteration during puberty or adolescence. These disorders represent diagnostic and therapeutic challenges, because they can be triggered by different nosological entities; and on the other hand, patients carrying the same pathologies can present different anatomical alterations. Laparoscopy plays an important role in the diagnostic approach of these patients because, besides the fact that it allows an excellent visualization of the internal genitals anatomy, it also allows tissue sample taking for histological studies. On the other hand, from a therapeutic point of view, laparoscopic surgery allows removal of internal structures opposed to the patient's definite gender. We report the case of an adolescent with ovotesticular disorder of sexual development (True Hermaphrodite) from whom, once his male gender was socially defined, the embrionary remnants derived from Muller were removed through laparoscopic approach. Mamoplastic reduction and testicular prosthesis implantation were also practiced through conventional surgery. PMID- 20306725 TI - [Immune response of Hansen's disease. Review]. AB - Hansen's disease presents a wide spectrum of clinical and histopathological manifestations that reflect the nature of the immunological response of the host towards diverse Mycobacterium leprae components. The immunological system, composed by both innate and adaptive immunology, offers protection towards infections of various etiologies, among them bacterial. Bacteria, of course, have developed multiple strategies for evading host defenses, based on either very complex or simple mechanisms, but with a single purpose: to "resist" host attacks and to be able to survive. We have tried to summarize some recent studies in Hansen's disease, with more emphasis in the inmunology area. We think that in the future, all illnesses should also be very strongly related to other important aspects such as the social, environmental and economic, and whose development is not solved in a laboratory. PMID- 20306726 TI - [Hypoxia in cancer malignity. Review]. AB - Hypoxia is a common characteristic of solid tumors. It contributes to local and systemic tumor progression, as well as the lack of response to radio and chemotherapy, therefore increasing the probability of tumor recurrence. The HIF-1 transcription factor is the main regulator of tumor adaptation to hypoxia stress, stimulating the expression of many genes that allow cells to survive under these conditions. Products dependent on HIF-1 factor are involved in processes of tumor progression, such as proliferation, glucose metabolism, ph-acidosis, angiogenesis and metastasis. It has become increasingly necessary to gain knowledge on the HIF 1 mechanisms of action, since it is possible to find inhibitors that could be used therapeutically against cancer. In this review, a summary is given on the role that the HIF-1 factor plays in hypoxia, as well as its implications on angiogenesis and metastasis. PMID- 20306727 TI - Current concepts in the diagnosis of primary open angle glaucoma. AB - BACKGROUND: Primary open angle glaucoma is characterized by quantifiable parameters including the intraocular pressure, the aqueous outflow facility, and geometric measurements of the optic disc and visual defects. Despite this, diagnosis remains controversial. OBJECTIVE: To review the current concepts in the diagnosis of primary open angle glaucoma and adapt them to situations where high technology facilities are lacking. DATA SOURCE: Information was obtained from journals/medline, Hinari, the American Academy of Ophthalmology preferred practice pattern CD, and reputable textbooks using publications from 1972 to 2007. RESULTS: The Preferred Practice Pattern Committee of the American Academy of Ophthalmology recommends that the comprehensive initial glaucoma evaluation (history and physical examination) includes comprehensive adult eye evaluation with special attention to those factors that specifically bear on the diagnosis such as the optic disc, nerve fibre layer and visual field evaluation, open anterior chamber angles on gonioscopy and absence of secondary causes of glaucoma. Intraocular pressure is no longer relied onin the diagnosis of primary open angle glaucoma. Sequential evaluation of optic disc cup and size, neuroretinal rim size and shape, retinal nerve fiber layer, presence of peripapillary atrophy, and presence of retinal or optic disc haemorrhages enhance the ability to detect glaucomatous damages. CONCLUSION: A simple systematic approach in examination of the optic discs and visual field will improve accurate diagnosis of glaucoma. PMID- 20306728 TI - Neurosurgical procedures in Jehovah's Witnesses: the Tema experience. AB - BACKGROUND: On account of religious reasons, Jehovah Witnesses do not accept blood or blood products; occasionally, they accept reinfusion of autologous blood via a cell saver during surgery. OBJECTIVE: The aim of this study was to document the demographics of Jehovah Witnesses undergoing neurosurgical procedures, the neurosurgical procedures undertaken in Jehovah Witnesses and to evaluate the complications of the procedures. METHODS: A retrospective audit of the medical records of all Jehovah's Witnesses who underwent neurosurgical procedures at our institution, from January 1st 2000 to December 31st 2006, was carried out. The parameters investigated included demographics, pre and post operative diagnosis, type of neurosurgical procedure and complications. RESULTS: Nineteen patients (fifteen male, four female; male/female 3.8:1) constituted the series. The mean age was 45.8 (range: 20-65) years. A total of 21 procedures were performed; intracranial surgery (33%), spinal surgery (67%). No autotransfusion of blood was given. Lumbar laminectomy for stenosis was the commonest spine procedure, ten (71.4%); craniotomy for tumor excision was the commonest intracranial procedure, six (85.7%). With respect to the whole series, the morbidity rate was 4.7% and the mortality rate was 4.7%; both were from intracranial surgery. CONCLUSION: It is possible to perform certain types of neurosurgical procedures in Jehovah's Witnesses without increasing the mortality and morbidity rate. PMID- 20306729 TI - Clinical and histological characteristics of nasopharyngeal cancer in Sokoto, north-western, Nigeria. AB - BACKGROUND: Cancer of the nasopharynx poses diagnostic and therapeutic difficulties because of the hidden nature of the nasopharyngeal space, which allows for significant spread of the disease before diagnosis and hence poor prognosis. OBJECTIVE: To describe the clinical and histological characteristics of nasopharyngeal cancer in a tertiarty health institution in Northern Nigeria. METHODS: Clinical features of patients with nasopharyngeal cancer presenting at the Ear, Nose and Throat clinic of a University Teaching Hospital in North western Nigeria seen over a five-year period were analysed. RESULT: A total number of 30 cases, [22 (73.3%) males and 8 (27.7%) females] with a male to female ratio of 2.8:1 were seen. The mean age was 39.1 years with the fourth decade of life recording the highest number of 16 cases (53.3%) and the least in the thirth decade. The commonest clinical features were neck swelling caused by cervical lymphadenopathy 28 (93.3%), epistaxis 25 (83.3%), nasal obstruction 20 (66.7%),and deafness 11 (36.7%). Others were otalgia 9 (30%), palatal swelling 8 (26.7%),cranial nerve involvement 7 (23.3%) and visual impairment 6 (20%). According to the UICC 1997 staging for nasopharyngeal carcinoma, 23 (76.7%) and 7 (23.3%) were T3 and T4 or stages III and IV respectively. The histological diagnoses were squamous cell carcinoma 23 (76.7%) cases, non-Hodgkins lymphoma 3 (10%) cases, plasmacytoma 2 (6.7%) cases, rhabdomyosarcoma one (3.3%) case, karposis sarcoma one (3.3%) cases. Seventeen (56.7%) patients though accepted in principle never went for radiotherapy. Only 2 (6.7%) were still alive three and six years respectively from the time of diagnosis after chemoradiation while all others (93.3%) had died within one year of diagnosis. CONCLUSION: Nasopharyngeal cancer in Northern Nigeria is characterised by presentation with advanced disease, high mortality and low 5-year survival rates. Free or highly subsidized medical programme for early detection and treatment will reduce the high mortality rate associated with nasopharyngeal cancer in this region. PMID- 20306730 TI - Spontaneous pre-labour rupture of membranes at term: immediate versus delayed induction of labour. AB - BACKGROUND: Spontaneous pre-labour rupture of membranes (SPROM) at term is one of the most common complications of pregnancy. It is an important cause of perinatal morbidity and mortality, particularly because it is associated with a latency period from membrane rupture to delivery. OBJECTIVE: To compare the outcome of labour in women who had immediate induction of labour, with those who had delayed induction following SPROM at term. METHODS: A prospective case control study of 200 women who had either immediate induction of labour with intravaginal misoprostol tablets, or delayed induction with intravenous oxytocin infusion after an expectant period of 12 hours, at Aminu Kano Teaching Hospital, Kano, Nigeria. The outcome of labour was compared in the two groups using the Z test and Chi square test, while, p-value of less than 0.05 was taken as significant. The odds ratio (OR) and 95% confidence interval were also determined where appropriate. RESULTS: Immediate induction of labour with intravaginal misoprotol resulted in lower rates of caesarean section and operative vaginal delivery, with a higher rate of spontaneous vaginal delivery. The duration of latent phase of labour and hospital stay before delivery was statistically significantly shorter in the immediate induction group. Neonatal and maternal morbidity were insignificant and comparable between the two groups. CONCLUSION: Immediate induction of labour with intravaginal misoprotol resulted in significantly lower rates of intervention without compromising fetomaternal outcome. We recommend the immediate induction of labour with proper use of intravaginal misoprotol in women with SPROM at term. PMID- 20306731 TI - Adenosine deaminase activity in subjects with normal pregnancy, pregnancy induced hypertension and pre-eclampsia. AB - BACKGROUND: Both pregnancy and adenosine deaminase (ADA) are associated with depressed cellular mediated immunity. There is little information on ADA activity in pregnant Africans. OBJECTIVE: To determine the serum levels of adenosine deaminase (ADA) in normal pregnancy and pregnancy complicated by hypertension in Nigerian women. METHODS: One hundred and twenty-five pregnant women comprising 35 normal non-pregnant women, 35 normal pregnant women, 35 pregnant women with pregnancy induced hypertension and 20 patients with pre-eclampsia were recruited for the study. Serum adenosine deaminase enzyme (ADA) activity was measured by the Giusti and Galanti spectrophotometric method in all study subjects. RESULTS: The mean serum ADA level in the non-pregnant women was higher than that in the normal pregnant women (23.21 +/- 6.3 v 14.69 +/- 3.2, p<0.001). Amongst the pregnant women, mean serum ADA in the hypertensive and pre-eclamptic women was significantly higher than that in the normal pregnant group (p<0.001). CONCLUSION: These findings indicate a probable decrease in cellular immunity in normal pregnancy and an enhanced cell mediated immunity in pre-eclampsia. PMID- 20306732 TI - A retrospective analysis of aetiology and management of epistaxis in a south western Nigerian teaching hospital. AB - BACKGROUND: Epistaxis is a common otolaryngological emergency and is often due to lesions within or around the nose and systemic conditions. Controlling epistaxis presents a challenge in the underdeveloped, resource-poor centres where there are limited facilities. OBJECTIVE: To describe the aetiopatogenesis of epistaxis in our hospitals. METHODS: This was a retrospective review of the cases of epistaxis managed at the Obafemi Awolowo University Teaching Hospitals Complex (OAUTHC), Ile Ife, over a three-year period: January 2003 - through December, 2005. Information on sociodemographic characteristics, clinical presentation and management of epistaxis was obtained from the hospital records both in the accident and emergency units and the ENT outpatient clinic. RESULTS: A total of 106 cases were managed during the period. The peak age incidence was in the 21-40 year group. There was a significant male preponderance, ratio 3.4:1. Trauma contributed to 75 (70.9%) of the cases managed. Maxillofacial injuries were the most common injury encountered (50.7%). This was mainly secondary to the road traffic accident (RTA). Malignant neoplasms were the second most common aetiological factor seen in this study while idiopathic causes were the third most common. There were two cases with systemic problems associated with renal failure. Nasal packing was adequate to control the epistaxis in most cases. Nasal packing was done with gloved finger cots and vasellinated gauze. Two patients (1.9%) had external carotid artery ligation. Eleven patients (10.4%) received blood transfusion. CONCLUSION: Epistaxis is a common presentation of head and neck trauma. Non-surgical control of epistaxis (nasal packing) is adequate in many cases. Reducing the incidence of trauma from RTA will reduce the incidence of emergency epistaxis in our centers. PMID- 20306733 TI - Influence of pregnancy on bone mass in sickle cell anemia. AB - BACKGROUND: Sickle cell disease (SCD) causes osteopenia and osteoporosis, This osteopenia may be further influenced by pregnancy. OBJECTIVE: To find out the effect of pregnancy on bone skeleton density in patients with SCD. METHODS: Consecutive adult female SCA patients who were treated at the out-patients clinics of King Fahd University Hospital Al-Khobar, Saudi Arabia, between January and July 2007, were the cases of study. Patient's age, number of pregnancies and duration after pregnancy were documented. Weight and height were recorded to calculate body mass index (BMI). Blood was collected for haematology and biochemistry purposes. Bone mineral density (BMD) measurement was done using dual energy X-ray absorbtiometry (DEXA) at upper femur and lumbar spine. RESULTS: Thirty-eight patients were evaluated. There were 20 (52.6%) patients who were delivered in (Group A) and 18 (47.4%) who were nulliparous in Group B. The average age in group A was 27.55 +/- 4.9 years while group B was 26.30 +/- 2.1 years. Thirteen (65%) of the patients in group A were osteoporotic when compared to five (27.7%) in group B (p=0.01). Osteopenic patients in group B were seven (38.9%) versus four (20%) in group A (p=0.2). Osteoporosis in both groups was highest at lumbar spine compared to the hip region (P=0.001). BMD was lower in parous women when compared to the nulliparous women. There was no significant difference in haematological parameters which included the percentage of sickle hemoglobin, hemoglobin level between normal, osteopenic and osteoporotic patient. CONCLUSION: This study shows that SCA female patients suffer from low bone mass in young age. Pregnancy predisposes the SCA patients to further osteopenia and osteoporosis. PMID- 20306735 TI - Fulfilling human resources development goal in West Africa: can the training of ophthalmologist diplomates be improved? AB - OBJECTIVE: To ascertain the perspectives of Trainee Ophthalmologist Diplomats (TOD) on the Ophthalmic Diploma Training (ODT) in West Africa with a view to improving the programme. METHODS: A survey of set 2005 TOD on ODT was carried out in Ghana, 2006. RESULTS: The trainees included 10 (83.35%) males and two (16.7%) females whose ages ranged between thirty-two and fifty-one years. The sponsors of the trainees included Sight Savers International, five (41.7%); Christian Blind Mission International, three (25.0%); Eye Foundation, Lagos, Nigeria two (16.7%); Ministry of Defence Nigeria, one (8.3%); and Health Authority Ghana, one (8.3%). Nine trainees (75.0%) felt the programme was well structured, training allowances were adequate eight (66.7%) and inadequate four (33.3%). Eleven (91.7%) trainees would work wherever they were posted; ten (83.3%) trainees had sense of fulfillment and three (25%) would like to proceed for residency training. All trainees were at least good in chalazion surgery and treatment of common medical eye conditions. Majority were at least good in eye surgery like cataract, eleven (91.7%); trabeculectomy nine (75.0%); pterygium 10 (83.3%); eyelid, eight (66.7%); destructive 11 (91.6%) and refraction 9 (75.0%). Some trainees' perceived problems included inadequate sponsorship (33.3%), short duration of the course four (33.3%) and poor accommodation facility two (16.7%). However, trainees' suggested increase in training posts, four (33.3); training allowance three (25.0%); and incentives for trainers/training hospitals two (16.7%). CONCLUSION: The ODT programme ensures ophthalmic manpower for secondary eye care level despite challenges. The stakeholders should look into problems facing the programme in order to improve it. PMID- 20306734 TI - Malignant gastrointestinal tumours in south western Nigeria: a histopathologic analysis of 713 cases. AB - BACKGROUND: Malignant tumours of the gastro-intestinal tract are not as rare as previous studies suggest. Recent studies have indicated increasing incidence. OBJECTIVE: To document the pattern, age and sex distribution as well as histopathology characteristics of malignant tumours of the gastro-intestinal system in Lagos and Sagamu in Southwestern Nigeria. METHODS: The paraffin embedded blocks and slides as well as pathology reports of malignant tumours of the gastrointestinal (GIT) organs collected from five laboratories (Morbid Anatomy Departments of the Lagos University Teaching Hospital and Olabisi Onabanjo University Teaching Hospital in Sagamu, Ogun State as well as the three private histolopathology laboratories in Lagos State) were reviewed. The clinical data such as the age, sex, and clinical summary were extracted from the records. RESULTS: About 80% (578 cases) of all the 713 malignant GIT tumours were epithelial; sarcomas, carcinoid and non-Hodgkin's lymphoma being less common. The ages ranged from 4-96 yrs (mean of 48.9 years) with the peak in patients 60-69 year age group and M:F ratio of 1.35:1. Colorectal tumours topped the list with 402 cases (56%), followed by liver 105 (14.7%), stomach 85 (12%) and omental metastases 67 (9.4%). The oesophagus, pancreas, small intestine and gall bladder represented 18 (2.5%), 16 (2.2%), 12 (1.7%), and eight (1.1%) respectively. Colorectal cancers peaked in the 60-69 year age group, liver and stomach cancer occurred mostly between the 50-59 years age group. Over half of the colorectal adenocarcinomata were located in the ano-rectum with 93 (23%) occurring in those below 40 years of age. CONCLUSION: Colorectal cancer remains the commonest GIT tumour in the region. Molecular studies are imperative to identify the common subtypes of GIT tumours in order to ascertain their specific pathogenetic and prognostic features. PMID- 20306736 TI - Foramina parietalia permagna in a Nigerian family. AB - BACKGROUND: Enlarged parietal foramina are defects in the skull and are believed to be benign and familial and caused by variable degree of defective intramembranous ossification of the parietal bones. They are rare and asymptomatic, usually associated with ALX4 or MSX2 gene mutations and transmitted as autosomal dominant. OBJECTIVE: To highlight the importance of plain radiographs in the diagnosis of this condition and need for health education in affected families. METHODS: A four-year-old male presented with a 14-day history of fever, seizures, and loss of consciousness. Full clinical and radiological evaluation was undertaken. RESULTS: Physical examination showed an unconscious boy who was having persistent twitching of the upper limbs. Investigations of skull X-rays which showed bilateral parasagital lucencies in the parietal bones. Ultrasound scan showed a mass in the posterior fourth ventricle. The father admitted to having defects in his skull. The patient's elder brother also had defects in his skull. CONCLUSION: The case illustrates that PFM is usually benign and mostly discovered accidently. In most cases, health education and reassurance are all that are necessary. PMID- 20306737 TI - A giant guteal schwannoma with extension into the pelvis: a case report. AB - BACKGROUND: Schwannomas are uncommon slow growing tumours arising from the nerve sheath or Schwann cell. OBJECTIVE: To report a case and the surgical removal of a giant complex schwannoma and to highlight the value of extensive investigations including a preoperative histologic diagnosis in the successful surgical management of uncommon large benign tumours. METHODS: A 39-year-old man presented with a 15-year history of a large mass in the right gluteal region. He was clinically evaluated, subjected to imaging studies and surgery. RESULTS: Clinical examination revealed a 40 cm by 60 cm mass in the right gluteal region and continuous with a 25 cm by 15 cm pelvic mass. The ultrasound scan revealed a very complex (mixed solid and fluid containing) gluteal mass with extension to the pelvis. The CT scan showed a very large, well defined lobulated tumour with cystic spaces and enhancing nodules. The tumour extended through the ischiadic foramen into the pelvis and posteriorly into the thigh muscles. A Doppler scan of the pelvic vessels revealed that the right common and internal iliac arteries were both compressed but not occluded. An incisional biopsy was reported as a Schwannoma with xanthomatous changes and an immuno histochemistry profile of S 100+, Ki-67+ (less than 1% of the cells). A right foot drop following the surgery responded to physiotherapy. The duration of total hospital stay was 12 weeks. CONCLUSION: The staged excision of large and complex schwannomas is safe. It is essential that a preoperative histological diagnosis is made to establish that the tumor is truly benign. PMID- 20306738 TI - Multiple digital grengrene arising from traditional therapy: a case report. AB - BACKGROUND: Traditional medicine has being advocated as an alternative to Orthodox medicine in Nigeria despite, its reported adverse effects. OBJECTIVE: To report an unusual complication of traditional therapy. METHODS: A 20-year-old house-wife who was bitten by a crawling insect presented to a hospital with complaints of swollen body and pain in three digits. After clinical evaluation and investigations, she had both medical and surgical intervention. RESULTS: Two weeks following an insect bite, the patient noticed periorbital and bilateral leg swellings. She sought help from a traditional medicine practitioner who incised and tied the affected digits for three days. He repeated the cycle thrice. She had generalized oedema, massive proteinuria, hypoalbuminaemia, hypercholesterolaemia features consistent with a diagnosis of nephritic syndrome. There was gangrene of the left middle finger and both index toes. Oedema responded to diuretics, lisinopril and low salt diet. She had surgery for the gangrenous digits. CONCLUSION: Development of gangrene is an unusual finding in nephrotic syndrome. It occurred in this case as an aftermath of traditional medical intervention. This report reiterates the danger of this form of medical practice and the need for measures to protect the populace to be put in place. PMID- 20306739 TI - Paradigm shift: duodenal ulcer to reflux esophagitis and its relation to the longitudinal prevalence of H. pylori. PMID- 20306740 TI - Palliative treatment in advanced hepatocellular carcinoma: has it made any difference? AB - Hepatocellular carcinoma (HCC) is a global health problem, the fifth most common cancer in the world. HCC occurs in a histologically abnormal liver due to underlying chronic liver disease resulting as a sequele of the chronic viral infections, hepatitis B and C. Since these two viral infections are endemic in Asia and Africa, more than 80% of cases are encountered in these regions. In India, a large proportion of the population is "at risk" for developing chronic liver disease and, therefore, HCC. Due to the lack of screening programmes in the country, the majority of HCC patients are diagnosed at an advanced stage of the disease, thus treatment remains a challenge. Palliative therapy forms the mainstay of treatment for this group of patients. The current era provides a plethora of options for the palliative management of HCC. This review concisely summarises the historical perspective and the current status of palliative treatment in advanced HCC. PMID- 20306741 TI - Hepatic hydrothorax. AB - Hepatic hydrothorax is defined as significant pleural effusion (usually greater than 500 mL) in a cirrhotic patient, in the absence of underlying pulmonary or cardiac disease. The diagnosis of hepatic hydrothorax should be suspected in a patient with established cirrhosis and portal hypertension, presenting with unilateral pleural effusion, most commonly right-sided. Hydrothorax is uncommon, and is found in 4-6% of all patients with cirrhosis and up to 10% in patients with decompensated cirrhosis. Although ascites is usually present, hydrothorax can occur in the absence of ascites. Patients with hepatic hydrothorax usually have advanced liver disease with portal hypertension and most of them require liver transplantation. Current insight into the pathogenesis of this entity has led to improved treatment modalities such as portosystemic shunts (TIPS) and video-assisted thoracoscopy for closure of diaphragmatic defects. These modalities may provide a bridge towards transplantation. PMID- 20306742 TI - Evaluation of eating habits in dyspeptic patients with or without Helicobacter pylori infection. AB - BACKGROUND: The prevalence of Helicobacter pylori infection varies in different societies and geographical locations. This is attributed to socioeconomic status, life style, family density and other factors. There is also a possibility of an association between eating habits and the prevalence of H. pylori infection. AIM: In this study, we examine the association between H. pylori infection and particular eating habits such as sharing plates, glasses and spoons. METHODS: This cross-sectional study was performed via a questionnaire-based evaluation of all patients with dyspepsia who underwent endoscopic assessment. Data including demographic information, endoscopic findings, H. pylori status and sharing of dishes within families were recorded. Individuals with a history of 3-day antibiotic treatment in the past month, or use of proton pump inhibitors in the past two weeks, or regular use of H2-blockers during the past week were excluded. The H. pylori status was determined using the rapid urease test. RESULTS: Of the 225 participants who had filled in the questionnaire, 204 were eligible; 92 were male (45.1%) and 112 female (54.9%) with 22% younger than 30 years of age, 49% between 30 and 50 years and 29% older than 50. In families where common dishes were used, the prevalence of H. pylori infection was significantly higher. (77% vs. 53%, p = 0.001) Factors such as age, sex, and education proved to be irrelevant. CONCLUSION: The results suggest a strong link between H. pylori infection and eating habits, thereby raising the possibility that modification of these habits might limit H. pylori infection. PMID- 20306743 TI - Intestinal parasitosis in school going children of Dharan municipality, Nepal. AB - This community-based investigation was carried out to estimate the prevalence of intestinal parasitosis in primary school-going children of the Dharan municipality, Sunsari, Nepal from 2007 through 2008. A total of 182 stool samples were collected from 101 male and 81 female children of ages 4 to 10 years. A questionnaire including the factors predisposing to parasitosis, was filled up by the parents of each child. Parasitic examination was carried out by direct wet mount examination and concentration method using 10% formol-ether. The prevalence rate was found to be 22.5%. The result revealed preponderance of Giardia lamblia (11.5%) followed by Entamoeba histolytica/dispar (4.4%), Ascaris lumbricoides (3.3%), hookworm (1.6%) and Enterobius vermicularis (0.5%). Statistically significant difference in the prevalence with respect to age and gender was not seen. However, socioeconomic status, type of toilet used and the practice of hand washing had a strong correlation (p < 0.05) with the prevalence of parasitic infection. Abdominal discomfort also had a strong statistical association (p < 0.05) with the prevalence of parasitic infection. Proportionally higher infection rate was seen in participants not using filtered or boiled water. Lack of education of mothers and children, improper toilets and failure to practice proper hand washing were perceived from this study as contributors to the acquisition of intestinal parasitic infections. PMID- 20306744 TI - Giant sigmoid diverticulum--report of two cases. PMID- 20306745 TI - Endoscopic removal of a coin impacted at the ileocecal valve with small bowel obstruction. PMID- 20306746 TI - Sigmoid perforation and mesocolic hematoma in a patient with polyarteritis nodosa. PMID- 20306747 TI - Cholecystocolic fistula: an unusual presentation and review of literature. PMID- 20306748 TI - Pantoea agglomerans liver abscess in a resident of Brazilian Amazonia. PMID- 20306749 TI - Acute mesenteric ischemia following colonoscopy: report from Brazilian Amazon region. PMID- 20306750 TI - Primary mesothelioma of the peritoneum. PMID- 20306751 TI - A case of congenital esophagobronchial fistula in an adult. PMID- 20306752 TI - Symptomatic giant duodenal diverticula. PMID- 20306753 TI - Clinical profile, prognostic indicators and outcome of Wilson's disease in children: a hospital based study. AB - BACKGROUND: Wilson's disease is a common metabolic disease of the tropics, which is treatable, if diagnosed early. In the paediatric group, the manifestations are mainly hepatic. AIMS: The objective was to study the varied presentations of the disease and to evaluate the diagnostic values of conventional tests in children. The prognostic importance of different indices in liver disorders was also assessed. METHOD: The prospective work was carried out in the Paediatric Medicine Department of Nilratan Sircar Medical College & Hospital (NRSMCH) over a span of three years on children 1 through 12 years of age who fulfilled the prerequisite inclusion criteria. RESULTS: The mean age of the 34 children was 7.7 +/- 2.13 years. Predominant liver involvement was seen in 17 patients, neurological disturbance in 7 and purely hematological manifestations in 2 cases; the remaining 8 children were incidentally diagnosed whilst screening the siblings of affected subjects. In our series the sensitivity of various diagnostic tests was: 24 hour urinary copper excretion--100%, serum ceruloplasmin less than 20 mg/ dL- 82.3%, K-F rings--32.35%. Eighteen of the 23 followed up cases (78.2%) responded to medical treatment. The sensitivity and specificity of the new Wilson Index was more than the Nazer index in predicting mortality with liver involvement. CONCLUSION: The superiority of the new Wilson Index over the Nazer index has to be validated on a larger scale. As the outcome of management was very promising, a high index of suspicion in pertinent cases can not only check mortality, but also prevent florid manifestations. PMID- 20306754 TI - Evaluation of ultrastructural changes by electron microscopy in neonatal cholestasis. AB - BACKGROUND: Biliary atresia (BA) and idiopathic neonatal hepatitis (NH) account for 50-70% of all cases with neonatal cholestasis. The treatment of the former is early surgical intervention, while the latter requires non-surgical supportive care. Failure to differentiate the two conditions may result in avoidable surgery in NH, which may significantly increase morbidity. The lack of differentiating clinical features, biochemical markers and other specific investigations to distinguish the two is still a major problem. AIM: This study was thus initiated to evaluate electron microscopic changes in the liver in patients with NH and BA, to correlate these with changes on light microscopy and look for specific differentiating features between the two. METHODS: Ten patients with neonatal cholestasis whose liver specimens were available for electron microscopic analysis were included in the study. There were 6 patients with BA and 4 patients with NH. RESULTS: Among the biochemical parameters, serum alkaline phosphatase and gamma glutamyl transpeptidase were significantly higher in BA than in patients with NH. On light microscopy, giant cell transformation was seen in 75% patients with NH and 33.3% of patients with BA. Even in BA, intracellular cholestasis was more prominent than ductular cholestasis (100% vs. 50%). Ductular proliferation was seen in 50% of NH patients and all patients of BA. Electron microscopy revealed prominent endoplasmic changes in all patients with NH and to a milder degree in BA. Changes in mitochondria and glycogen content were similar in both groups. CONCLUSION: Ultrastructural changes in neonatal cholestasis seen through electron microscopy are largely non-specific and do not differentiate BA from NH. PMID- 20306755 TI - Comparative study of low pressure versus standard pressure pneumoperitoneum in laparoscopic cholecystectomy--a randomised controlled trial. AB - INTRODUCTION: Standard pressure pneumoperitoneum for laparoscopic cholecystectomy employs a pressure range of 12-14 mm Hg. An emerging trend has been the use of low pressure pneumoperitoneum in the range of 7-10 mm Hg in an attempt to lower the impact of pneumoperitoneum on the human physiology while providing adequate working space. Our study proposes to compare the use of low pressure pneumoperitoneum with the use of standard pressure pneumoperitoneum. METHODS: A randomised controlled trial consisting of 60 patients with symptomatic gallstone disease who underwent laparoscopic cholecystectomy, of which 30 patients were subjected to standard pressure pneumoperitoneum during the procedure and 30 patients to low pressure pneumoperitoneum. RESULTS: Both groups were comparable in all aspects. The mean operating time with low pressure pneumoperitoneum was 49.07 +/- 5.72 minutes and with standard pressure pneumoperitoneum was 46.43 +/- 6.92 minutes. There was no statistically significant change in blood pressure, heart rate, pain at 6 hours, need for additional analgesia or shoulder tip pain with the use of lower pressure pneumoperitoneum. CONCLUSIONS: Low pressure pneumoperitoneum benefits the patient in the form of lower intensity of postoperative pain but it does not positively impact intraoperative hemodynamics. PMID- 20306756 TI - Myalgia during interferon therapy--does it warrant monitoring muscle enzymes? AB - Myositis during interferon therapy is a known but rare adverse event. However the clinician may overlook the symptom-complex of proximal muscle weakness and myalgia, seen in myositis, since myalgia is a commonly reported side effect of therapy. In this context then, is there a role for monitoring muscle enzymes to detect subclinical myositis in patients on interferon therapy? We prospectively monitored the creatine kinase (CK) and lactate dehydrogenase (LD) levels in all our patients who reported myalgia during treatment and noted that muscle enzymes remained within normal range throughout the duration of treatment. This excluded the possibility of subclinical myositis in myalgic patients and thus led us to conclude that routine monitoring of muscles enzymes is neither necessary nor beneficial. PMID- 20306757 TI - Boom in clinical research industry: a dangerous trend. AB - Over the last decade or so India has witnessed a phenomenal growth in the clinical trial industry. The projections forecast a continuing growth of this trend. It has been predicted that by 2011 India will be in charge of 15% of global clinical trials. The enthusiasm for the growth of this industry in India is shared not just by the major pharmaceutical companies and CROs but also equally so by government agencies. The raison d'etre for medical research is that it should lead to maximum possible benefit to the largest number of people. Hence, an examination of the extent to which public good is served can act as a measure for objective analysis of this exponential increase in the clinical trial industry. After all it is the health and lives of the people that are at stake. On the face of it, it would seem that all trials testing the safety and efficacy of various molecules, by their very nature work towards public welfare as they are indispensible to the development of any drug including the life-saving ones. An increasing number of clinical trials at all stages in a product's life cycle are funded by the pharmaceutical industry. It would then seem that the industry sponsored medical research is necessarily furthering the larger objective of human wellbeing. However, the operations of the pharmaceutical industry, the nature of the processes involved and the operative motives are a bit too complex to facilitate this larger objective so simply, just as yet. This warrants a closer look at the various aspects of industry-sponsored clinical research. PMID- 20306758 TI - Suicidal behavior in Latinos: focus on the youth. AB - The multicultural nature of American society presents clinicians and mental health providers with the unique challenge of working with mentally ill patients from many different cultural backgrounds. Although research investigating suicidal behavior among Latinos is limited, the literature suggests the presence of two distinct phenomena: (a) the prevalence of completed suicide among Latinos as a group is lower than the national rate and (b) the prevalence of suicidal behavior among Latino youth between the ages of 10-24 years is greater than in other ethnic groups, especially among females. Acculturation, family conflicts, physical abuse and sexual abuse, among other factors, have been suggested to increase the risk of depression and suicide among young Latinos. To ameliorate suicidal behavior among Latino youth, more research is needed about specific risk factors, diagnosis, treatment, and ultimately, suicide prevention. Research focused on identifying risk and mediating factors for suicidal behavior in young Latinos is particularly relevant, given the size and rapid growth of the Latino population in the United States of America. PMID- 20306759 TI - Meta-analysis of positive effects, side effects and adverse events of holistic mind-body medicine (clinical holistic medicine): experience from Denmark, Sweden, United Kingdom and Germany. AB - About 50% of the general population has a chronic disease not cured by biomedicine. OBJECTIVES: Meta-analysis of holistic clinical medicine for which chronic patients were treated and outcomes were, 1) global quality of life, 2) self-rated physical/mental health, quality of life or ability of functioning, or 3) patients felt cured for a specific disease of dysfunction. METHOD: MEDLINE and PsycLNFO and specific journals were searched in January 2009. RESULTS: Eleven clinical studies (18,500 participants) were identified. Positive effects: Quality of life Number Needed to Treat (NNT) = 2, physical health problems NNT = 3, mental health problems NNT = 2, sexual dysfunctions NNT = 2, self esteem NNT = 2, working/studying ability NNT = 2, anorgasmia NNT = 1, other specific sexual dysfunctions NNT = 2. Of 791 patients treated was 617, or 78.0% cured (NNT = 1). Side effects and adverse events: re-traumatization Number Needed to Harm (NNH) > 18,500; brief reactive psychosis (if mentally ill) NNH = 4,625; brief reactive psychosis (if not mentally ill) NNH > 9,250; brief reactive psychosis, all patients NNH = 9,250; depression NNH > 18,500; depersonalization and derealization NNH > 18,500; iatrogenic disturbances NNH > 18,500; minor bone fractures (ribs, hand) NNH = 4,625; serious bone fractures (spine, scull, pelvis) NNH > 18,500; suicides during or less than three month after therapy NNH > 18,500; suicide attempts during or less than three month after therapy NNH > 18,500. Suicide was prevented NNT = 1. Therapeutic value TV = NNH/NNT = 9,250. CONCLUSIONS: Holistic clinical medicine is an efficient complementary and alternative medicine (CAM) treatment for chronic illnesses and health related problems. Every second patient with physical and mental disorders, sexual dysfunctions, and existential problems were healed. Holistic clinical medicine had no significant side effects or adverse events. PMID- 20306761 TI - Evidence-based medicine: four fundamental problems with the randomized clinical trial (RCT) used to document chemical medicine. AB - Randomized clinical trials (RCT) have been accepted as the golden standard of testing, thus making chemical medicine "evidence based". The RCT is based on four assumptions: 1) The placebo effect is represented by a placebo pill, 2) it is possible to make a double-blind test with biologically active drugs, 3) beneficial and harmful effects of drugs are fairly measured in RCTs, and 4) an appropriate time frame for the test is used. We have found problems with these assumptions: 1) The placebo effect provided by close relationships to a physician is stronger than an inert pill, 2) double-blind tests cannot be made with biologically active drugs, as these leave an internal clue in the patient that destroys the blinding (active placebo), 3) lack of global outcome measures makes toxic effects invisible for the test and magnifies minor effects to make clinically insignificant positive effects look important, and 4) RCTs are used in such a brief time frame that side effects and harm are not properly detected. The four errors combine into a serious error: The RCT-procedure induces a strong bias in favor of any toxic drug tested. RCTs can turn drugs that are only toxic and not beneficial at all into products sold as.useful chemical medicine. Many pharmaceutical drugs on the market today are tested only with this flawed RTC procedure, and we recommend that these drugs be tested again using a rational method. If drugs are not more helpful than placebo, then we should return to classic psychosocial holistic medicine. PMID- 20306760 TI - A review of familial correlates of child and adolescent obesity: what has the 21st century taught us so far? AB - With the rising prevalence rates of child and adolescent obesity over the last several decades, it is important to examine the extant research to inform future research. OBJECTIVE: The aim of this paper was to review and critique research investigating familial correlates of child and adolescent obesity in the last decade. METHODS: A literature review was conducted between March 2008 and December 2008. Studies published after 2000 that assessed familial associations with child and adolescent obesity in the parental, family functioning, and sibling domains were included in the review. A total of 80 studies met the inclusion criteria. RESULTS: The majority of studies focused on the parental domain. Substantial evidence indicates an association between authoritative parenting style and child/adolescent lower BMI, healthy dietary intake, and physical activity. Also, research on family meals has consistently shown an association between the frequency of family meals and child/adolescent lower BMI and healthy dietary intake. CONCLUSION: To date, preliminary evidence suggests that familial factors are associated with child and adolescent obesity, dietary intake, physical activity, and weight control behaviors, but most of the evidence is cross-sectional and there are limitations to the research. Recommendations for future research are discussed. PMID- 20306762 TI - Physical self-esteem, a five year follow-up study on Swedish adolescents. AB - This study describes the levels and inter-correlations of physical self-esteem, physical activity, body mass index (BMI), and body fat and, in addition, distinctive of individuals with high vs. low physical self-worth in a longitudinal design during adolescence. METHODS: At mean ages 12.7, 15.7, and 17.7 years, physical activity (steps/day) was measured for four consecutive schooldays of 77 (41 girls) Swedish adolescents. Perceived physical self-esteem, height, weight, and at ages 15.7 and 17.7 years, body fat percent was also measured. RESULTS: Boys' physical self-perception scores were higher than girls' and an overall stability during adolescents was seen. High and low physical self worth had a significant impact regarding BMI at ages 12.7 and 17.7 years and regarding body fat at age 17.7 years in both boys and girls. CONCLUSIONS: Regression analysis indicated that BMI and body fat counter-predicted self-worth in girls age-dependently. Efforts to build adapted physical activity programs for overweight and obese are emphasized. PMID- 20306763 TI - Self perception score from zero to ten correlates well with standardized scales of adolescent self esteem, body dissatisfaction, eating disorders risk, depression, and anxiety. AB - The ability to quickly and reliably assess mental health status would assist health workers, educators and youth workers to provide appropriate early intervention for adolescents. OBJECTIVE: To investigate the validity of a simple self perception score out of ten by correlating the self perception scores of adolescents from a normal, community sample of adolescents with their scores on standardized mental health measures. Study group was 470 early adolescent students aged 11.0-14.5 years from grades 7 and 8 in two secondary schools. METHODS: Self perception was self reported using a score of zero to ten points, and the scores were then correlated with scores on the Harter Self Perception Profile, Beck Junior Depression, Speilberger State and Trait Anxiety and the Eating Disorders Inventory. A High Risk group (self perception < 5) was assessed to examine how many of these adolescents also had poor self esteem and risk for depression, anxiety, and eating disorders. RESULTS: Self perception scores correlated positively with self esteem and self concept subscales and it was negatively associated with depression, state and trait anxiety, and EDI scores. Of the 15.1% high risk adolescents in the overall sample, 78% scored below the group average on the mean of all Harter Self Concept scores; 70% scored above average for Beck Depression; 64% and 74% scored above average on Speilberger State/Trait Anxiety respectively; 80% scored higher than the average on the group mean EDI. CONCLUSIONS: A self perception score from zero to ten can be a simple and accurate way of gaining an initial insight into the current mental health status of adolescents. PMID- 20306765 TI - An interpretative phenomenological analysis of the lived experiences of young Chinese females in the course of unintended pregnancy. AB - Research in the West has increasingly recognized the importance of understanding the perceptions and experiences of young pregnant females; however, limited studies are available in Chinese societies. This paper investigates the experiences of 10 young pregnant Chinese females living in Hong Kong. Through the use of individual interviews and the method of interpretive phenomenological analysis, the researchers were able to explore how the research participants made sense of their personal and social worlds. This research strategy also adds a cultural perspective in analyzing their stories in the context of Hong Kong. Recurrent themes identified in their stories revealed their thoughts, feelings, and actions in encountering the unintended pregnancy. The themes can be grouped into four categories, namely 1) pregnancy resolution: self-determination vs. significant others' influences; 2) emotional experiences after the termination of pregnancy: sense of relief vs. sense of guilt and sadness; 3) identity of young pregnant females: self-perception vs. others' perceptions and 4) pursuing an intimate relationship: love vs. sex. The findings provide a knowledge base for an understanding of the perspectives of young pregnant women and open up valuable reflections and discussions about adolescent pregnancy in Chinese societies. Implications can also be drawn for intervention, prevention, and research. PMID- 20306764 TI - The negative consequences of other students' drinking: inventory development and assessment of differences by student characteristics and risk behaviors. AB - College students continue to report being disrupted by other students' alcohol use. OBJECTIVE: This study was designed to develop measures to document the consequences resulting from other students' drinking and identify differences in experiencing these consequences by student characteristics and drinking behaviors. STUDY GROUP: A stratified random sample of undergraduate students (N = 3,908) from ten universities in North Carolina, USA, completed a web-based assessment. METHODS: Exploratory factor analysis (EFA) was performed on the random first split-half sample (n = 1,954) to identify factor structure. Confirmatory factor analysis (CFA) was performed on the remaining half sample (n = 1,954) using structural equation modeling. RESULTS: EFA revealed two inventories: interpersonal and community consequences of others' drinking inventories. CFA on the second split-half sample identified model fits for the two factor structure suggested by EFA. Of 3,908 participants, 78% reported experiencing one or more consequences due to others' drinking during the past 30 days. Multivariable generalized linear mixed modeling further validated the inventories and resulted in several associations. Male students who reported getting drunk experienced significantly more interpersonal consequences from others' drinking (p < .001). Minority students, students who lived on campus and students who reported getting drunk experienced significantly more community consequences from others' drinking (p < .01). CONCLUSIONS: These findings demonstrate that 4 out of 5 college students experience consequences from others' drinking, and consequences vary for different subgroups of students. Although these inventories should be tested further, these findings propose standardized measures that may be useful to assess the consequences of others' drinking among college students. PMID- 20306766 TI - Impact of socioeconomic and health related factors on the iron status of adolescent girls from two boarding schools in Southern Benin. AB - To our knowledge, the impact of socioeconomic and health related factors on the iron status of adolescent girls has never been studied in Benin. OBJECTIVE: These factors were studied in 180 girls aged 12 to 17 years living in two boarding schools from South Benin. METHODS: Iron deficiency (ID) was defined as either serum ferritin (SF) < 20 microg/L or SF between 20-50 microg/L plus two abnormal values in the three following parameters: serum iron < 11 micromol/L, total iron binding capacity > 73 micromol/L or transferrin saturation < 20%. Socioeconomic and health related factors were obtained from each participant by mean of an interview using a standardized and pre-tested questionnaire. RESULTS: Almost half the participants reported some health problems in the last four months before the study, whereas more than 75% auto-medicated before going to the hospital. The majority of the girls believed themselves to be in good health, although only 16% could define the term 'anemia'. Multivariate regression analysis indicated that girls whose mother was a manual worker (P = .002), who came from a larger family (P = .0001), and who auto-medicated (P = .014), had a lower hemoglobin level, whereas girls who had started their menstruation (P = .008) had a lower SF level. In a logistic regression analysis, girls from a large family size and whose mother was a manual worker showed a higher risk of IDA (OR = 3.5; 95% CI = 1.1 2.5; P = .04; OR = 3.0; 95% CI = 1.2-2.2; P = .04 respectively). CONCLUSION: The findings indicate that iron deficiency is related to the occupation of the mother, family size, auto-medication, and menstruation. PMID- 20306767 TI - Menstrual function in female high school cross-country athletes. AB - Menstrual function in adolescent athletes has received limited investigation. OBJECTIVE: In a sample of female high school cross-country (XC) athletes, the purposes of the investigation were to (1) describe menstrual function (history and inseason), (2) describe the relationship between menstrual function and variables including body mass index (BMI), high school year, current year of running, total years running, training distance, racing pace, additional organized sport participation other than XC, and participation in XC practices and races, (3) determine the relationship between menstrual function and self reported interfering exercise related leg pain (ERLP), and (4) determine the relationship between menstrual function history and menstrual function during a XC season. STUDY GROUP: 62 female high school XC athletes. METHODS: A prospective cohort design was used. Athletes were asked to complete an initial questionnaire querying several variables including menstrual function and ERLP history. At the end of the XC season, athletes were asked to complete a postseason questionnaire regarding menstrual function and ERLP during the XC season. RESULTS: Of the athletes, 25.8% (16/62) reported abnormal menstrual function history and 34.9% reported abnormal menstrual function inseason. Abnormal menstrual function history was a risk for previous interfering ERLP (RR = 3.00, CI: 1.09, 8.29), and abnormal menstrual function history was a risk for abnormal menstrual function inseason (RR = 4.11, CI: 1.75, 9.62). CONCLUSIONS: Abnormal menstrual function was present in this sample of athletes and was a risk for previous interfering ERLP and future episodes of abnormal menstrual function. PMID- 20306768 TI - HPV vaccination coverage among adolescents aged 9 to 17 years in a United States military treatment facility. AB - Human papilloma virus (HPV) is expected to infect 80% of the United States female population. The vaccine Gardasil protects against four types of HPV. Routine administration of Gardasil began at Womack Army Medical Center (WAMC) in November 2006. This research looks at vaccine compliance among girls aged 9 to 17 years. Medical records of all females aged 9 to 17 enrolled at WAMC (n = 6,154) were examined using the Composite Health Care System (CHCS) database. Patients identified with CPT code 90649, HPV vaccine were included. Of girls enrolled at WAMC, 22.9% (n = 1,406) began the vaccine series. Among girls aged 9 to 17 years age, only 25.7% completed the entire 3 injection series; 34.6% received 2 injections, and 39.7% received 1 dose (P = .006). WAMC falls slightly below the national norm in administering the Gardasil vaccination series. Because at least six months is required to complete the series, however, some patients who received the first dose might not have had sufficient time to complete the series during the data collection period. Findings show that 77% of girls aged 12 to 17 years have not yet been vaccinated. PMID- 20306769 TI - Juvenile primary fibromyalgia syndrome in an inpatient adolescent psychiatric population. AB - The purpose of this study was to identify the clinical and demographic characteristics of adolescent females admitted to a psychiatric hospital who meet the criteria for Juvenile Primary Fibromyalgia Syndrome (JPFS). METHODS: Participants (n = 62) were adolescent females, ages 12 to 18 years who were admitted to an inpatient psychiatric unit. The participants completed four questionnaires: The Achenbach Youth Self-Report (YSR), the Children's Somatization Inventory (CSI), the Fibromyalgia Impact Questionnaire modified for children (FIQ-C) and the Pain Symptom Questionnaire (PSQ). Then participants were interviewed to assess the Yunus and Masi JPFS criteria. The interview included an examination of 21 (18 bilateral and 3 control) tender points. RESULTS: Of the 62 adolescent females enrolled, 52% (n = 32) met criteria for JPFS (i.e. JPFS cases). Both the FIQ and CSI scores were significantly elevated for JPFS cases as compared with non-cases (p = .0001 and p = .0012 respectively). Cases of JPFS also scored significantly higher on the anxiety, depression, and conduct disorder scales of the YSR. No between-group differences were found in reports of physical or sexual abuse. However, a consistently higher percentage of JPFS cases reported physical or sexual abuse as a child. CONCLUSIONS: Juvenile primary fibromyalgia is highly prevalent in an adolescent inpatient psychiatric unit. This possibility should be taken into consideration when chronic complaints of pain are expressed by patients in this setting, especially in those who have conduct-related issues. The connection between JPFS and abuse history requires further investigation. PMID- 20306770 TI - An evaluation of intervention strategies for HIV/AIDS in Trinidad and Tobago (2000-2007). AB - To evaluate the impact of health promotional strategies against The Acquired Immune Deficiency Syndrome (HIV/AIDS) in Trinidad and Tobago. METHODS: The HIV/AIDS Morbidity and Mortality reports were used to chart the pattern of change in the incidence of new HIV positive cases for the years 2000-2007 to determine the decrease in new HIV positive cases after 2004 with the implementation of the National Strategic Plan as well as What's Your Position (WYP), KNOW Your Status and Get Tested Now campaigns. These effects were tested using a quasi experimental, post exposure design. A cross-sectional survey using street intercept interviews provided data on intervention effectiveness. Logistic regression analysis was used to determine the impact of HIV/AIDS campaigns, using their respective objectives. RESULTS: The study showed that a 16% decline in new HIV positive cases began during 2003 and 2004 and continued to decline by smaller margins until 2007. Data collected from the 599 participants with exposure to at least one campaign found that 92.7% reported awareness of WYP, followed by GTN (71.1%), RIU (42.6%), KYS (38.4%) and OUCH! (8.5%). 23.7% participants reported condom use post program exposure, whereas 19.0% practiced informed abstinence. A relationship was found between KYS and HIV/ AIDS Testing (p = .016) and between RIU and increased condom use (p = .010). CONCLUSIONS: Since the implementation of the programs, there have been positive lifestyle modifications among the sample population. Particularly "WYP" has been particularly effective in increasing awareness of practicing abstinence, faithfulness to one partner, condom usage when applicable, knowing their HIV status and further educating themselves about HIV/AIDS. PMID- 20306771 TI - An analysis of gender differences in self-reported health, use of medicines and access to information sources about medicines among adolescents. AB - Adolescence is a key period in the emergence of gender differences in health that persist into adulthood. Knowledge about health-related gender differences among adolescents could be instrumental in informing policy and practice to effect health improvement among this age group. The main objectives of this study were therefore to investigate gender differences in self-reported health complaints and use of medicines during the preceding 3 months and access to information sources about medicines among adolescents in Malta. A self-administered questionnaire was distributed among adolescents attending secondary schools in Malta. A stratified random sample design generated a sample size of 514 students. Common health complaints, use of medicines, and sources of information about medicines were investigated by means of author-designed checklists. The analytical sample was formed from 474 usable questionnaires collected from students aged 14-16 years, of which 53.8% were females. In general, a female excess emerged for health complaints and use of medicines except for sport injuries and use of vitamins. Gender differences were statistically significant for a female excess in the retrieval of information from the package insert (p < .001), parents or adult relatives (p < .01) and friends or schoolmates (p < .05). The findings of this study underscore the need for awareness of gender differences in the health of adolescents among health care providers, policy makers, and educators. An important implication of the findings is that the health needs of adolescents could be more equitably addressed by adopting a holistic patient-oriented approach particular to the health needs of each individual. PMID- 20306772 TI - Talking about sexuality at secondary schools of periurban area of Dhaka city. AB - Adolescents constitute 23 percent of population in Bangladesh yet access to information and education on reproductive health is limited for them. OBJECTIVE: To determine the effect of introducing an education booklet on reproductive health knowledge among the adolescents and its acceptability to them. STUDY GROUP: Students of grade IX and X in eight secondary schools (both boys and girls schools) of periurban location of Dhaka city. METHOD: A quasi-experimental pre post test design study was conducted during October 2004 to May 2005. The intervention was distribution of an education booklet and conduction of a health education session at the respective classes. RESULTS: Total number of respondents were 1,490 (862 during pre test and 628 during post test). About 4% of parents never attended school, whereas 10.7% of fathers and 3.2% of mothers were graduates. A greater proportion of adolescents could correctly narrate the physiological changes of adolescence, duration of menstrual cycle, fertile period, leucorrhoea, masturbation, and night emission in the post test. Almost all adolescents stated that health education was necessary and should be given in secondary schools. About 95% stated that the education booklet was necessary. They appreciated that the language was easy and fluent, the illustration was meaningful, and some suggested a few modifications. CONCLUSION: Providing reproductive health information to adolescents can be sustained through inclusion in school curriculum and has the potential to produce health benefits in future. PMID- 20306773 TI - Assessing the association between pesticide exposure and cognitive development in rural Costa Rican children living in organic and conventional coffee farms. AB - We examined the association between pesticide exposure and cognitive development among rural Costa Rican children in a cross-sectional study. Study participants aged 4-10 years included 17 children whose parents worked in La Amistad organic coffee plantation and 18 Las Mellizas children whose parents worked in their own small conventional coffee farms. Two spot-urine samples were collected from each participant and analyzed for organophosphorus and pyrethroids pesticide metabolites. We administered the computerized Behavioral Assessment and Research System (BARS), a figure-drawing task, and a long-term memory test to evaluate study participant's cognitive development. Although urinary pesticide metabolite levels did not vary considerably between these two groups of children, we found that Las Mellizas children performed better in BARS and the figure drawing tests than did La Amistad. The results from the linear mixed-effects models suggested that family socioeconomic status (SES) might be a significant contributor to the variation of the outcomes of the neurobehavioral tests. The effect of pesticide exposure, however, as measured in a snapshot fashion, did not play a significant role to the performance of the cognitive development evaluation. Regardless of the study limitations, needed effort should be devoted to the improvement of the SES on the La Amistad families so that their children's cognitive development would not be compromised further. Additionally, future studies should focus on addressing the limitations imposed on the snapshot assessment of pesticide exposure and on conducting cognitive development evaluation so the link between childhood pesticide exposure and their cognitive development can be thoroughly investigated. PMID- 20306774 TI - Physical activity and health among adolescents with cerebral palsy in Sweden. AB - Cerebral palsy (CP) is the most common disorder of movement and posture in children. The disorder results from a non-progressive brain lesion occurring in the fetal or infant brain. Children with CP have challenges with movement, posture, and mobility that last a life time. Few studies describe physical activity and health among adolescents with CP. AIM: The aim of this study was to describe self-related health, physical activity, and body complaints among adolescents with CP in Sweden. METHODS: A questionnaire was answered by 64 adolescents with CP, with 143 adolescents without disabilities serving as controls. RESULTS: Adolescents with CP reported their general health to be better than adolescents without disabilities (p = .001). Adolescents with CP participated less than adolescents without disabilities in sport during recreation time (p = .009). About 19% of adolescents with CP were never or seldom physically active, compared with 8% in the control group (p = .025). A total of 50% of adolescents with CP reported musculoskeletal complaints during the last three months, compared with 69.5% in the control group. There was a correlation between musculoskeletal complaints and self-related health in adolescents with CP (p = .015) but not in the controls. CONCLUSION: Adolescents with CP reported their general health to be good. Adolescents with CP were less physically active than adolescents without disabilities. There was a correlation between musculoskeletal complaints and self-related health among adolescents with CP. Further research is needed to determine the cause of the low physical activity among adolescents with CP and also to determine the relationship between musculoskeletal complaints and physical activity. PMID- 20306775 TI - Correlations between the blood pressure and other health variables in Spanish adolescents. AB - The aim of this paper was to study the correlations between blood pressure and other health variables in Spanish adolescents. 204 boys and 270 girls (aged 13-17 years, with written parental consent,) from 18 private and 17 public educative centers from 16 of 21 districts of the city of Madrid, constituted the representative sample. 12.7% of the boys and 35.6% of the girls were inactive or sedentary. Socioeconomic status significantly determined the physical activity of girls, especially in the age group 16-17 years. The tobacco consumption by girls was significantly greater than by boys. A significant inverse relation of tobacco consumption with physical activity was found for boys. Among the girls, 47.4% were lightly overweight to obese as opposed to 14.7% of boys. A significant association between adiposity and physical activity in the girls was observed. The averages for the systolic/diastolic blood pressure were 125.6/71.3 mm Hg in boys and 118/69.4 mm Hg in girls. A significant relation between gender and systolic blood pressure was found. A relation between physical activity and diastolic blood pressure for boys was observed (69.9 mm Hg for active or very active and 74.1 mm Hg for moderately active to sedentary). The lack of existing relations between blood pressure and others variables support the hypothesis that these variables require a longer-term to become obvious cardiovascular risk factors. We believe, therefore, that girls and those from lower socioeconomic status should receive high-priority attention concerning health-related habits. PMID- 20306776 TI - [Child and adolescent psychiatry and psychotherapy research report]. PMID- 20306777 TI - [Child and adolescent psychiatry and psychotherapy research report. Introduction and overview]. PMID- 20306778 TI - [Obesity and overweight]. PMID- 20306779 TI - [Affective disorders]. PMID- 20306780 TI - [Anxiety disorders]. PMID- 20306781 TI - [Attention deficit hyperactivity disorder]. PMID- 20306782 TI - [Elimination disorders]. PMID- 20306783 TI - [Autism]. PMID- 20306784 TI - [Parent-child relations, marital quality]. PMID- 20306785 TI - [Diagnosis]. PMID- 20306786 TI - [Drug monitoring and regulatory aspects of psychotropic drugs in childhood and adolescence]. PMID- 20306787 TI - [Epidemiology]. PMID- 20306788 TI - [Eating disorders]. PMID- 20306789 TI - [Hare Forensic and Psychopathy Checklist]. PMID- 20306790 TI - [Mental handicap]. PMID- 20306791 TI - [Basic research]. PMID- 20306792 TI - [Child guidance and school]. PMID- 20306793 TI - [Children of impaired parents]. PMID- 20306794 TI - [Child welfare risk, abuse]. PMID- 20306795 TI - [Physical illnesses]. PMID- 20306796 TI - [Quality of life]. PMID- 20306797 TI - [Education]. PMID- 20306798 TI - [Neuroleptic adverse effects with emphasis on weight gain]. PMID- 20306799 TI - [Personality disorders and self-injury behavior]. PMID- 20306800 TI - [Post traumatic stress disorder and dissociation]. PMID- 20306801 TI - [Prevention]. PMID- 20306802 TI - [Schizophrenia]. PMID- 20306803 TI - [Learning disorders]. PMID- 20306804 TI - [Miscellaneous topics]. PMID- 20306805 TI - [Language development, speech and language disorders]. PMID- 20306806 TI - [Social behavior disorders]. PMID- 20306807 TI - [Addictive disorders]. PMID- 20306808 TI - [Partial) inpatient treatment]. PMID- 20306809 TI - [Tic disorders]. PMID- 20306810 TI - [Obsessive-compulsive disorders]. PMID- 20306811 TI - Castor bean, Ricinus communis. PMID- 20306812 TI - Oral allergy syndrome: a clinical, diagnostic, and therapeutic challenge. AB - OBJECTIVES: To provide a review of the literature and discuss the clinical, pathophysiologic, diagnostic, and therapeutic challenges of oral allergy syndrome (OAS). DATA SOURCES: English-language publications on OAS (and pollen-food allergy syndrome) were identified through MEDLINE and through the reference lists of each identified article and review. STUDY SELECTION: Articles pertaining to OAS with respect to its varied clinical presentation, underlying pathophysiology, available and investigational diagnostic testing, and evidence-based treatment options were selected. RESULTS: OAS occurs in patients with a prior cross reactive aeroallergen sensitization and clinically presents with initial oralpharyngeal symptoms after ingestion of a triggering fruit or vegetable. Although controversial, these symptoms may progress to systemic symptoms outside the gastrointestinal tract in 8.7% of patients and anaphylactic shock in 1.7%. OAS's underlying pathophysiology may play a role in clinical presentation and outcome, depending on whether the cross-reactive protein is a heat-labile PR-10 protein, a partially labile profilin, or a relatively heat-stable lipid transfer protein. Diagnostic testing is variable based on the underlying food tested, but fresh food skin prick test typically has the highest sensitivity. Treatment centers on avoidance and the consideration of self-injectable epinephrine. Because of its relationship with a cross-reactive aeroallergen sensitization, subcutaneous immunotherapy and sublingual immunotherapy have also been therapeutically tried with mixed results. CONCLUSION: OAS is a challenging diagnosis to the practicing allergist because of its many clinical, diagnostic, and therapeutic considerations. Understanding these challenges and their underlying mechanisms can facilitate a knowledgeable approach to treating an oral allergy patient. PMID- 20306813 TI - Is the maintenance and reliever approach the answer? AB - OBJECTIVE: To examine the efficacy of the maintenance and reliever (M+R) approach in the treatment of asthma exacerbations. DATA SOURCES: PubMed, MEDLINE, and Cochrane database searches using the key words formoterol and budesonide, dynamic dosing, adjustable dosing, and M+R therapy. STUDY SELECTION: Articles were selected based on their relevance to the topic of this review. RESULTS: Several studies have examined dynamic dosing of the long-acting beta-agonist formoterol combined with budesonide in the treatment of asthma. Most of these studies have shown reductions in asthma exacerbations. Although obvious concern arises regarding increase in dose of the long-acting beta-agonist component, no significant signal of morbidity or mortality has been seen. Potential concerns regarding the studies performed thus far include the fact that all have been sponsored by the pharmaceutical industry and have required beta-agonist response as an inclusion criterion. CONCLUSIONS: Although many of the data regarding this approach are positive, not all the studies have demonstrated efficacy. It is hoped that future non-pharmaceutical company-sponsored research will clarify this issue and, should efficacy be confirmed, shed light on the mechanism of action. PMID- 20306814 TI - Psychometric validation of the rhinitis control assessment test: a brief patient completed instrument for evaluating rhinitis symptom control. AB - BACKGROUND: Allergic rhinitis is common, but a validated tool for comprehensive assessment of disease control is not available. OBJECTIVE: To develop a simple patient-completed instrument (the Rhinitis Control Assessment Test [RCAT]) to help detect problems with control of rhinitis symptoms. METHODS: During a visit to an allergy specialist, 410 patients with allergic rhinitis completed a Total Nasal Symptom Score (TNSS) assessment and the 26-item developmental RCAT. Physicians also completed a global assessment of rhinitis symptom control for each patient. RESULTS: Stepwise regression methods identified 6 items from the developmental RCAT (frequency of nasal congestion, sneezing, and watery eyes; sleep interference; activity avoidance; and self-assessed control) that were most predictive of the allergist's global rating of rhinitis symptom control. A summated rating scale from these 6 items showed good convergent validity (r > 0.70) with scale scores from the TNSS. The discriminant validity of the 6-item scale was demonstrated as mean RCAT scale scores differed significantly across groups of patients differing in physician-rated disease severity (F = 54.4), TNSS severity (F = 193.8), and physician-recommended change in therapy (F = 50.6) (P < .001 for all). CONCLUSIONS: The RCAT, a 6-item patient-completed instrument, has satisfactory psychometric properties and seems to be a valid tool for assessing control of allergic rhinitis. Further validation studies will provide confirmation. PMID- 20306815 TI - A comparison of asthma prevalence and morbidity between rural and urban schoolchildren in Arkansas. AB - BACKGROUND: Asthma disproportionately affects minority and low-income children. Investigations that focus on high-risk pediatric populations outside the inner city are limited. OBJECTIVE: To compare asthma prevalence and morbidity in urban and rural children in Arkansas. METHODS: We administered a validated survey to parents of children enrolled in urban and rural school districts in Arkansas. Rates of asthma diagnosis, asthma symptoms, medication use, and health care utilization were compared between urban and rural groups. RESULTS: Age and sex distributions were similar; however, 85% of rural and 67% of urban children were black and 78% of rural and 37% of urban children had state-issued medical insurance (P < .001 for both). Provider-diagnosed asthma was similar in the rural vs urban groups (19% vs 20%); however, rural children were more commonly diagnosed as having chronic bronchitis (7% vs. 2%, P < .001). Rural children had more asthma morbidity compared with urban children, including recurrent trouble breathing (odds ratio [OR], 1.9; 95% confidence interval [CI], 1.5-2.2), recurrent cough (OR, 2.2; 95% CI, 1.9-2.6), recurrent chest tightness (OR, 1.8; 95% CI, 1.5-2.2), and repeated episodes of bronchitis (OR, 2.2; 95% CI, 1.7-2.8) during the preceding 2 years. Rural children were more likely to report symptoms consistent with moderate to severe asthma compared with urban children (46% vs. 35%, P < .001). There were no differences in health care utilization between groups. CONCLUSION: Asthma prevalence was similar between representative rural and urban groups in Arkansas, but asthma morbidity was significantly higher in the rural group. PMID- 20306816 TI - Use of herbal remedies and adherence to inhaled corticosteroids among inner-city asthmatic patients. AB - BACKGROUND: Complementary and alternative medicines (CAM), such as herbal remedies, are widely used by patients with chronic diseases, such as asthma. However, it is unclear whether use of the herbal remedies is associated with decreased adherence to inhaled corticosteroids (ICSs), a key component of asthma management. OBJECTIVE: To examine the association among use of herbal remedies, adherence to prescribed ICSs, and medication and disease beliefs. METHODS: We surveyed 326 adults with persistent asthma who received care at 2 inner-city outpatient clinics. Patients were asked about CAM use (teas, herbs, and rubs) for the treatment of asthma in the prior 6 months. Medication adherence was assessed using the Medication Adherence Report Scale, a validated self-report measure. Univariate and multiple regression analyses were used to assess the relationship among herbal remedy use, adherence to ICSs, and medication and disease beliefs. RESULTS: Overall, 25.4% (95% confidence interval, 20%-30%) of patients reported herbal remedy use. Univariate analyses showed that herbal remedy use was associated with decreased ICS adherence and increased asthma morbidity. In multivariable analysis, herbal remedy use was associated with lower ICS adherence (odds ratio, 0.4; 95% confidence interval, 0.2-0.8) after adjusting for confounders. Herbal remedy users were also more likely to worry about the adverse effects of ICSs (P = .01). CONCLUSIONS: The use of herbal remedies was associated with lower adherence to ICSs and worse outcomes among inner-city asthmatic patients. Medication beliefs, such as worry about ICS adverse effects, may in part mediate this relationship. Physicians should routinely ask patients with asthma about CAM use, especially those whose asthma is poorly controlled. PMID- 20306817 TI - Thaumatin-like protein and baker's respiratory allergy. AB - BACKGROUND: Baker's asthma and rhinitis are among the most common occupational diseases. Inhaled cereal flours, such as wheat, especially cause this disease. OBJECTIVE: To identify and test in vivo clinically important wheat allergens in baker's respiratory allergy in a Finnish population. METHODS: Potential wheat allergens were purified using chromatographic methods from salt-soluble protein extracts of wheat flour and were used in skin prick tests with serial 10-fold dilutions (0.5-0.005 mg/mL). Twenty patients with baker's rhinitis, asthma, or both participated in this study. All the patients had positive skin prick test reactions and specific IgE antibodies to wheat flour. The control group consisted of 10 healthy individuals. Molecular identities of purified wheat allergens were characterized using sodium dodecyl sulfate-polyacrylamide gel electrophoresis and tandem mass spectrometry. RESULTS: Allergen concentrations of 0.3-0.5 mg/mL revealed that 12 patients reacted to a-amylase inhibitor (alpha-AI), 9 to peroxidase I (PI), 9 to thaumatin-like protein (TLP), and 6 to lipid transfer protein 2G (LTP2G). Conversely, with allergen concentrations of 0.05 mg/mL, 5 patients responded to alpha-AI, 3 to PI, 4 to LTP2G, and 6 to TLP. Of these, TLP and LTP2G are now observed to be new allergens associated with baker's asthma. CONCLUSIONS: In addition to the earlier-described alpha-AI and PI, TLP and LTP2G are important in vivo wheat allergens in baker's allergies in Finland. Further studies are needed to elucidate the role of these novel wheat allergens in respiratory disorders. PMID- 20306818 TI - Effects of summer mailing on in vivo and in vitro relative potencies of standardized timothy grass extract. AB - BACKGROUND: Allergen extracts can degrade when exposed to temperatures significantly beyond the optimum storage recommendation of 4 degrees C. Many allergen extracts are mailed to their final destinations throughout the year with exposure to varied environmental conditions. OBJECTIVE: To evaluate the effect of summer mailing on the in vitro and in vivo potency of timothy grass extract. METHODS: Standardized timothy grass extracts, 10,000 and 100,000 BAU/mL, were mailed round-trip between San Antonio, Texas, and Phoenix, Arizona, during August 2007. In-transit temperatures were recorded using a portable temperature logger. After mailing of the extracts, we performed quantitative in vitro enzyme-linked immunosorbent assay inhibition and in vivo ID50 EAL (Intradermal Dilution for 50 mm Sum of Erythema Determines Bioequivalent Allergy Units) analysis. RESULTS: Measured extract exposure temperatures were greater than 20 degrees C for 11 days and 30 degrees C for 6 hours during standard mailing in weather temperatures exceeding 38 degrees C. Enzyme-linked immunosorbent assay inhibition results for the 100,000- and 10,000-BAU/mL control samples were 97,900 and 10,580 BAU/mL, respectively, and for the mailed extracts were 96,800 and 7830 BAU/mL, respectively. These measurements fell within the current Food and Drug Administration lot release limits (67%-149%) and stability limits (50%-200%) relative to the standardized reference. The ID50EAL determinations of the control vs mailed extracts were 12.98 vs. 12.28, 12.66 vs. 12.32, and 11.97 vs 11.70 for the 3 patients. These differences were not statistically significant. CONCLUSIONS: Mailing of timothy grass extract produced no significant reductions in in vitro relative potencies or in vivo skin test reactivity in 3 sensitive patients. PMID- 20306819 TI - The effects of omalizumab on IgE-induced cytokine synthesis by asthmatic airway smooth muscle cells. AB - BACKGROUND: Human airway smooth muscle cells (ASMCs) express high- and low affinity IgE receptors and respond to IgE, thereby contributing to airway inflammation. OBJECTIVE: To determine whether anti-IgE antibodies (omalizumab) block the response of ASMCs to IgE in patients with asthma. METHODS: Airway smooth muscle cells, isolated from the biopsy specimens of patients with asthma, patients with chronic obstructive pulmonary disease, and control participants (6 in each group), were stimulated with IgE with and without omalizumab treatment, and cytokine secretion was determined by enzyme-linked immunosorbent assay, and messenger RNA (mRNA) secretion by real-time polymerase chain reaction, over 24 hours. IgE receptor expression was determined by immunoblotting. RESULTS: IgE stimulated mRNA synthesis encoded for interleukin (IL) 6, IL-8, and tumor necrosis factor a in ASMCs via mitogen-activated protein kinases, extracellular signal-regulated kinase 1/2, or p38. The secretion of the respective cytokines increased significantly: IL-6, IL-8, and tumor necrosis factor a at 6 hours and IL-4 at 24 hours. Cytokine mRNA synthesis and protein secretion were inhibited by omalizumab in a dose-dependent manner. The expression of low- and high-affinity IgE receptors was not altered by omalizumab in ASMCs. CONCLUSIONS: Omalizumab reduced IgE-stimulated synthesis and secretion of proinflammatory cytokines by human ASMCs. These findings imply a beneficial action of omalizumab in asthma therapy. This effect is not restricted to inflammatory cells; it also includes tissue-forming cells. PMID- 20306820 TI - A randomized, placebo-controlled study of intravenous montelukast in children with acute asthma. AB - BACKGROUND: Up to 30% of patients require hospitalization for acute asthma despite standard therapy in the emergency department. In adults, intravenous montelukast added to standard therapy significantly improved forced expiratory volume in 1 second (FEV1) and reduced hospital admissions compared with standard therapy alone. OBJECTIVE: To evaluate the efficacy of intravenous montelukast added to standard therapy in children with acute asthma. METHODS: This was a randomized, double-blind, placebo-controlled, multicenter study of children aged 6 to 14 years conducted from August 25, 2005 to March 17, 2008. Patients with an FEV1 of 75% or less of the predicted value after up to 120 minutes of standard therapy (e.g., oxygen, albuterol, inhaled anticholinergics, and systemic oral corticosteroids) were randomized to intravenous montelukast, 5.25 mg (n=145), or placebo (n=131) added to standard therapy. The primary end point was the time weighted average change in FEV1 during 60 minutes (deltaFEV1[0-60 min]). Secondary end points included the percentage of patients in whom treatment failed (patients who required hospitalization or for whom a decision to discharge was not reached within 2 hours after drug administration) and the change from baseline in modified pulmonary index score after 60 minutes of treatment. RESULTS: Montelukast was not significantly more effective than placebo for deltaFEV1[0-60 min] when added to standard therapy (0.08 vs. 0.07 L; least squares mean, 0.01; 95% confidence interval, -0.06 to 0.08; P = .78). No significant differences were found in the percentages of patients in whom treatment failed or the modified pulmonary index score after 60 minutes. Both treatments were well tolerated. CONCLUSIONS: In this study of children with acute asthma, intravenous montelukast was not significantly better than placebo in improving FEV1, symptoms, or overall hospital course. PMID- 20306821 TI - A comparison of 4 epinephrine autoinjector delivery systems: usability and patient preference. AB - BACKGROUND: Prefilled epinephrine autoinjectors are sometimes improperly used by patients, caregivers, and physicians. A user-centered design process led to the development of 2 prototype epinephrine autoinjectors (INT01 and INT02) that have a unidirectional perceived injection end, a self-retracting needle, and, with INT02, voice instructions to assist in guiding users through administration. OBJECTIVE: To compare the usability and patient preference among 4 epinephrine autoinjectors: EpiPen, TwinJect, INT01, and INT02. METHODS: A total of 48 participants were divided equally among 3 age groups: 7 to 10, 11 to 15, and 16 to 55 years. In each group, half had prior TwinJect or EpiPen training. In 1-hour sessions, without training, participants performed simulated-use testing under observation for all 4 epinephrine delivery systems. Usability (i.e., the ability to perform the manufacturer's labeled instructions), task completion time, and preferences were assessed and analyzed based on device, age, previous experience, sex, device malfunction, and testing order. RESULTS: More participants correctly followed all device instructions with INT02 (22 [46%]) than with INT01 (13 [27%]), EpiPen (6 [12%]), or TwinJect (0 [0%]). The difference among devices was significant (P < .01) after adjusting for device malfunctions and age group (the youngest age group [those aged 7-10 years] performed significantly worse than the other 2 groups). Prior experience, sex, and testing order did not significantly affect this measure. The first choice of overall preference was greater (P < .001) for INT02 (35 participants [73%]) vs. INT01 (7 participants [15%]), EpiPen (5 participants [10%]), and TwinJect (1 participant [2%]). CONCLUSION: The user centered device design may have a significant impact on correct epinephrine autoinjector use and patient preference. PMID- 20306823 TI - Serum interleukin 9 in allergic rhinitis. PMID- 20306822 TI - Allergy to pumpkin and crossreactivity to pollens and other foods. PMID- 20306824 TI - Dapsone hypersensitivity syndrome during delayed pressure urticaria treatment. PMID- 20306825 TI - Problems in breast pathology revisited. Preface. PMID- 20306826 TI - Epitheliosis, infiltrating epitheliosis, and radial scar. AB - The lesion termed "infiltrating epitheliosis" (IE) by Azzopardi is described using his original criteria. The differential diagnosis from radial scar (RS) is discussed. It appears that IE and RS are histologically and histogenetically different and are also associated with a different risk of carcinoma. IE can be associated with either in situ or invasive carcinoma, whereas RS being more like a process of involution is very seldom involved by a carcinoma. Therefore, whatever name is used among the several found in the literature, it should be made clear they are not interchangeable when reporting on lesions like IE and RS. PMID- 20306827 TI - Papilloma and papillary carcinoma. AB - Papillomas and papillary carcinomas differ in their 3 fundamental characteristics: the geometric properties of their fronds, the amount of their stroma, and the characteristics of their epithelium. Fibrosis at the edge of papillomas often entraps glands and creates the spurious impression of invasion. The proliferation of surface epithelial cells of papillomas does not give rise to unexpected diagnostic difficulties, but glandular proliferation within the stalks of papillomas often simulates the appearance of cribriform ductal carcinoma in situ. Needle biopsies of papillomas can deposit clusters of benign cells in a distribution that resembles an invasive carcinoma. Although papillomas overrun by ductal carcinoma in situ exhibit a papillary architecture, other features differentiate them from conventional papillary carcinomas. The presence of basal carcinoma cells with clear cytoplasm ("dimorphic" cells) and the formation of short stubby fronds sometimes cause pathologists to mistake papillary carcinomas for papillomas, and the bland cytologic characteristics of solid papillary carcinomas can lead to the same error. Conventional papillary carcinomas typically invade in a blunt manner. This phenomenon complicates the recognition of invasion by many papillary carcinomas and has given rise to controversy about the nature of the lesion classically known as "intracystic papillary carcinoma." PMID- 20306828 TI - Clinging carcinoma: an American perspective. AB - In 1979, Professor John Azzopardi introduced the term "clinging carcinoma" to describe what he considered to represent examples of ductal carcinoma in-situ (DCIS) characterized by "neoplastic cells . . . limited to the periphery of the containing structures." He emphasized that these lesions can be easily missed "since the alteration is cytological rather than anatomical." Two types of clinging carcinoma were described by Azzopardi. He considered the first to represent a variant of high-grade DCIS, and most pathologists concur with that view. In contrast, pathologists have been much more reluctant to accept Azzopardi's second type of clinging carcinoma as a type of DCIS, particularly in the United States. This second type is characterized by cells with low grade, monomorphic-type cytologic atypia, similar to the cells comprising low-grade DCIS with solid, cribriform, and micropapillary architectural patterns. Recent morphologic, immunophenotypic, and genetic studies have provided strong evidence that this lesion, described by Azzopardi as a type of clinging carcinoma (and now commonly referred to as flat epithelial atypia), does in fact represent a precursor to or an early stage in the development of DCIS, essentially validating the histologic observations made by Azzopardi more than 30 years ago. PMID- 20306829 TI - Flat ductal intraepithelial neoplasia of the breast: evolution of Azzopardi's "clinging" concept. AB - Thirty years ago, John G. Azzopardi described a mainly cytologically defined atypical intraepithelial lesion of the breast, which he called "clinging carcinoma in situ," a variant of "ductal carcinoma in situ." The lesion was characterized by replacement of native epithelial cells by very few cell layers of mildly to severely atypical epithelial cells. Based on the degree of cytologic atypia, Azzopardi distinguished type 1 with highly atypical nuclei and type 2 with merely subtle cytologic (nuclear) atypia. Although this distinctive lesion remained widely unrecognized and/or ignored by many pathologists for a long period, several recent studies strongly suggest its neoplastic nature. The aim of this review is to focus on the "clinging" concept and its evolution after the first description. The diagnostic criteria, main diagnostic pitfalls, immunohistochemistry, molecular-genetic findings, and the relevance of this type of lesion for clinicians and histopathologists are discussed. Rational for adopting a more appropriate terminology and classification, namely flat ductal intraepithelial neoplasia are also discussed. It is concluded that the "clinging" or flat lesion represents one of the earliest morphologically recognizable neoplastic breast lesions. This lesion is important, if one tries to better understand the tumorigenesis of early precursor lesions of the breast. This type of breast lesion is an indicator for coexisting neoplastic lesions, such as low grade ductal intraepithelial neoplasia (atypical ductal hyperplasia/low-grade ductal carcinoma in situ) and lobular intraepithelial neoplasia. PMID- 20306830 TI - Lobular breast carcinoma and its variants. AB - Lobular carcinoma is a special type of breast cancer that shows distinct clinical presentation, morphologic and molecular features, and clinical behavior, and its incidence is rising in recent years. Infiltrating lobular carcinoma (ILC) and its precursor lesions may result in diagnostic difficulties, particularly in the screening settings and their management may be problematic. Variants of lobular carcinoma, such as the pleomorphic variant, although not common, exist and some show differences in behavior warranting their recognition in view of requirements for different management strategies. Here we present a review of lobular carcinomas with particular attention to lobular in situ lesions, epidemiology, subtypes, diagnosis, molecular pathology, and grading of ILC in addition to the clinical behavior, response to therapy, and outcome of patients with ILC. PMID- 20306831 TI - The origins of early breast carcinoma. AB - Assessing the distribution of the in situ and invasive components of breast carcinomas and the extent of the disease represent an integrated part of our diagnostic routine. In this article, we summarize findings from 792 consecutive breast carcinoma cases, each documented in large-format histology slides. Selected cases were also analyzed in thick, large sections. Of these, 35.0% (42/120) of the purely in situ carcinomas were diffuse and occupied mostly larger ducts, whereas 37.5% (45/120) were multifocal and involved several distant terminal ductal-lobular units (TDLUs). The proportion of unifocal in situ cases involving a single TDLU or several neighboring TDLUs was 27.5% (33/120). Forty one percent (136/332) of early (< 15 mm) invasive carcinomas and 40.0% (136/340) of larger invasive tumors contained only a single invasive focus, with or without an in situ component within it. The remaining tumors were nonunifocal because of multiple invasive or multiple in situ foci or both. The proportion of extensive nonunifocal cases within purely in situ, early invasive, and more advanced invasive cases were 45.0% (54/120), 42.5% (141/332), and 42.4% (144/340), respectively. The results are discussed in the context of recent molecular genetic findings and the sick lobe theory. Elements that are congruent with the classical views of Professor Azzopardi expressed over 3 decades ago will be pointed out. Breast carcinoma seems to develop within a field of genetic alterations, often at multiple sites, and a considerable proportion of the cases comprise extensive lesions occupying a tissue space > or = 40 mm in all tumor size categories. PMID- 20306832 TI - Neuroendocrine differentiation in breast cancer: established facts and unresolved problems. AB - Neuroendocrine breast carcinoma (NEBC) diagnosis relies on (i) presence of morphologic neuroendocrine features, and (ii) neuroendocrine markers expressed in more than 50% of tumor cells. The World Health Organization classification describes 3 main histologic types: the solid, the small/oat cell, and the large cell variant. In addition, we have recently proposed a further categorization into 5 subgroups: the first 3 categories encompass solid lesions and include (i) solid cohesive carcinomas, (ii) alveolar carcinomas, and (iii) small cell carcinoma; the last subgroups include mucin-producing tumors which are (iv) solid papillary carcinomas and (v) cellular mucinous carcinomas. Chromogranin A and synaptophysin have been considered as the most sensitive and specific neuroendocrine markers in NEBC. At the molecular level, recent gene expression profiling studies have shown that NEBCs pertain to the luminal molecular type, being positive for hormone receptors and negative for HER2. Moreover, it has been demonstrated that mucinous and neuroendocrine carcinomas are transcriptionally distinct from conventional invasive ductal carcinomas. Following the above criteria, NEBCs constitute approximately 1% of all breast carcinomas. The clinical effect of neuroendocrine breast cancer is still a matter of debate; however, when compared with unselected breast cancers, NEBCs show a less aggressive clinical behavior. PMID- 20306833 TI - Salivary gland-type tumors of the breast: a spectrum of benign and malignant tumors including "triple negative carcinomas" of low malignant potential. AB - Salivary gland-type neoplasms of the breast are uncommon and comprise numerous entities analogous to that more commonly seen in salivary glands. The clinicopathologic spectrum ranges from benign to malignant but there are important differences as compared with those of their salivary counterpart. In the breast, benign adenomyoepithelioma is recognized in addition to malignant one, whereas in the salivary gland a histologically similar tumor is designated as epithelial-myoepithelial carcinoma without a separate benign subgroup. Mammary adenoid cystic carcinoma is a low-grade neoplasm compared with its salivary equivalent. It is also important to appreciate that in contrast to "triple negative" conventional breast carcinomas with aggressive course, most salivary type malignant breast neoplasms behave in a low-grade manner. Most of these tumors are capable of differentiating along both epithelial and myoepithelial lines, but the amount of each lineage-component varies from case to case, contributing to diagnostic difficulties. Well established examples of this group include pleomorphic adenoma, adenomyoepithelioma, and adenoid cystic carcinoma. Another family of salivary gland-type mammary epithelial neoplasms is devoid of myoepithelial cells. Key examples include mucoepidermoid carcinoma and acinic cell carcinoma. The number of cases of salivary gland-type mammary neoplasms in the published data is constantly increasing but some of the rarest subtypes like polymorphous low-grade adenocarcinoma and oncocytic carcinoma are "struggling" to become clinically relevant entities in line with those occurring more frequently in salivary glands. PMID- 20306834 TI - Breast pathology: beyond morphology. AB - Breast cancer is a heterogeneous disease and pathologists have evolved a system of classification that reflects this heterogeneity as well as provide prognostic and predictive information to manage patients. Professor Azzopardi's contribution to understanding and classifying breast disease is significant and reflected by the many articles in this issue. Nonetheless, there are limitations to the morphologic classification and new molecular methods promise to refine the biological understanding as well as provide better biomarkers for prognostication and targets for the development of novel therapeutics. The degree to which the new methods add value to the morphology remains to be seen, but there is hope that a symbiosis between morphology and molecular techniques will advance traditional histopathology and improve the care of patients with breast cancer. PMID- 20306836 TI - Profession's popular image. PMID- 20306835 TI - Commission will call for enhanced pay and authority for ward leaders. PMID- 20306837 TI - Going all out for Haiti. AB - The aftermath of the Haitian earthquake poses a huge challenge for nurses and other healthcare staff working in makeshift conditions. PMID- 20306838 TI - Uncharted territories. AB - RCN general secretary Peter Carter is to visit Gaza to help boost mental health services in the occupied Palestinian territory. PMID- 20306839 TI - A carer's perspective. Interview by Lynne Pearce. AB - In the fourth article in the series on managing change, Julie Newby describes how she improved end of life care and Stephen Wright analyses the skills she used. PMID- 20306840 TI - Numbers for newborns. AB - Newborns are screened for congenital conditions. To make tracking easier, a numbering system will become mandatory from April. PMID- 20306842 TI - Disseminating best practice at conferences. AB - This article, the first in a five-part series, discusses the skills required to present information and study findings at conferences. The article explores the ways in which best practice might be most successfully disseminated, through either verbal or poster presentations. In subsequent issues of Nursing Standard the author examines the dissemination of best practice through publication, taught sessions, workshops and electronic forms of communication. PMID- 20306843 TI - Care of patients undergoing intra-vitreal therapy. AB - This article discusses the role of the ophthalmic nurse in the care of patients with wet age-related macular degeneration who are undergoing intra-vitreal therapy. It provides an overview of the condition, its classification, clinical features, aetiology, diagnosis and treatment, and explains the implications for future nursing practice. A proactive, evidence-based and holistic approach to nursing care is emphasised throughout the article. PMID- 20306844 TI - Improving self-management for patients with long-term conditions. AB - An increasing number of people are living with long-term conditions. These conditions cannot be cured, but can be managed through education, health promotion, medication, therapy and self-management. Self-management involves people taking responsibility for their own health and wellbeing, as well as learning to manage any long-term illnesses. Nurses play a pivotal role in providing advice, guidance, education and support to people living with long-term conditions. Self-management is important as it not only benefits the patient, but also provides wider opportunities for community and specialist nurses to use and develop their clinical and interpersonal skills. PMID- 20306845 TI - Coaching interventions. PMID- 20306846 TI - Hurdles to understanding. PMID- 20306847 TI - In patients' interests. Interview by Danielle Weekes. PMID- 20306848 TI - A contentious area. PMID- 20306849 TI - [A comparison between anatomical landmark registration and surface registration for computer-assisted endoscopic sinus surgery]. AB - OBJECTIVE: To evaluate the clinical advantage and disadvantage of anatomical landmark registration (ALR) and surface registration (SR) in computer-assisted endoscopic sinus surgery (CAESS). METHOD: Twenty-six patients were selected for the CAESS, the preparatory times and mean target registration errors (TRE) were recorded in order to compare the difference between them two, their convenience and their value were also analyzed. RESULT: CAESSs were successfully used in 26 cases without complications. The average preparation time of SR was (8.5 +/- 1.9) minutes, that of ALR was (6.5 +/- 1.7) minutes. In the SR group, the TRE of naso labial angle was (1. 43 +/- 0.26) mm, that of front end of middle turbinate was (1.92 +/- 0.47) mm, that of front end of inferior turbinate was (1.82 +/- 0.49) mm, and that of back end of inferior turbinate was (2.03 +/- 0.42) mm. Them in ALR group were (1.58 +/- 0.35) mm, (2.05 +/- 0.37) mm, (1.92 +/- 0.31) mm and (2.48 +/- 0.64) mm, respectively. 24 cases (92. 2%) were not affected or were slightly affected by the navigation system. The value of navigation was affirmative in 22 cases (84. 6%), and its value was mainly related to TRE. CONCLUSION: The accuracy of surface registration was superior to that of anatomical landmark registration, but the anatomical landmark registration was more convenient and need less preparation time. The value of navigation system is its accuracy, convenience and no disturbance to surgery. The navigation system is more valuable in the complex cases than that in the general case. PMID- 20306850 TI - [The expression and significance of interleukin-17 and the infiltrating eosinophils in nasal polyps and nasal mucous of allergic rhinitis]. AB - OBJECTIVE: To observe the expression of interleukin-17 and the infiltration of eosinophilic cells in nasal polyps and allergic rhinitis, and investigate the roles of IL-17 and eosinophils in the etiology of nasal polyps and allergic rhinitis. METHOD: A study was conducted on 21 patients of nasal polyps, 18 ones of allergic rhinitis and 12 normal individuals. Immunohistochemical stain with the rabbit monoclonal antibodies of IL-17 was carried out. The eosinophilic cells infiltrated in different tissues were stained with HE, then counted under high power filed. The data was analyzed with ANOVA of SPSS12.0 software. RESULT: Many IL-17 stained cells were found in the samples of nasal polyps and allergic rhinitis, which were significantly higher than those in normal individuals (P < 0.05). Positive cell number in tissues of allergic rhinitis was similar to that in nasal polyps, but higher than in normal individuals. As for HE staining, there was no significant deviation of numbers of eosinophilic cell in tissue between allergic rhinitis and nasal polyps,while which differed from the normal ones (P < 0.05). CONCLUSIONS: 1. IL-17 is a newly cytokine which expressed in mucosa of allergic rhinitis and nasal polyps tissue. It indicates the degree of immunological reaction and inflammatory reaction, and can be used as an index to research the mechanism of nasal polyps as well as allergic rhinitis. 2. The eosinophilic cells count was correlated with the amount of IL-17 positive cells in nasal polyps and with allergic rhinitis correlation coefficients were R = 0. 606 (P < 0 01)and R = 0.446 (P < 0.05) respectively. It seems that eosinophils, which are regulated by IL-17, play an important roles in the development of nasal polyps and allergic rhinitis. PMID- 20306851 TI - [Efficacy evaluation of specific immunotherapy with standardized dermatophagoides pteronyssinus extract for allergic rhinitis accompanied with asthma]. AB - OBJECTIVE: To evaluate the efficacy of specific immunotherapy (SIT) with standardized dermatophagoides pteronyssinus extract for allergic rhinitis (AR)accompanied with asthma. METHOD: One hundred and fifty-five patients (40 AR with asthma, AR & asthma) in accordance with the inclusion criteria of SIT, were allocated to receive standardized Dermatophagoides pteronyssinus extract (SIT group, n = 89) or medical treatment (control group, n = 66). AR with or without asthma was observed separately. Symptom and medicine scores, quality of life were recorded and analyzed before and after 1 year treatment. Side effects were registered. Subjective evaluation of symptoms was made by the patients. RESULT: Rhinitis and asthma symptom scores, medicine scores and quality of life were greatly improved in SIT group of AR & asthma after 1 year, which were not significant changed in control group except for medicine scores. The subjective evaluation of symptoms was also significantly improved in SIT group. In patients of AR without asthma, the symptom scores, medicine scores and quality of life were both improved. The SIT group improved greater than that of control group. CONCLUSION: The clinical efficacy of patients with AR & asthma was not good with simple medical treatment, while great clinical efficacy could be acquired with SIT. PMID- 20306852 TI - [The correlative study between skin prick test with antigens and nasal provoking test in patients with allergic rhinitis]. AB - OBJECTIVE: To study the distribution of allergens in our district and the correlation between skin prick test with antigen and nasal provoking test in patients with allergic rhinitis. METHOD: A total of 1400 cases with allergic symptoms and signs underwent skin prick test with standardized aero antigens provoking by Allergo Phamar Company. The patients allergic to Dermatophagoides with different scale of the skin prick test were taken nasal provoking test in order to evaluate the correlation between skin prick test and nasal provoking test. RESULT: One thousand and eighty-eight (78%) cases showed a positive result in skin prick test. The percent of patients with positive skin prick test were as follows: 462 cases of Dermatophagoides pteronyssinus, 428 cases of Dermatophagoides farinae. Positive perennial aero antigens were 52.2% (568), positive seasonal aero antigens were 35.7% (388). All the patients of the scale of skin prick test was +++ and ++++ were positive. There are 29 patients were positive with nasal provoking test which the scale of skin prick test was ++. There are 21 patients were positive with nasal provoking test, which the scale of skin prick test was +. CONCLUSION: The correlation between skin test with antigens and nasal provoking test in patients whose positive scale were +++ and ++++. There are false positive in the patients whose positive scale were + and ++. The specific immunotherapy should consider the scale of the skin prick test and eliminate the false positive before the therapy. PMID- 20306853 TI - [Survey of quality of life in the patients with revision endoscopic sinus surgery]. AB - OBJECTIVE: To explore the effect of revision endoscopic sinus surgery (RESS) on quality of life in the patients with chronic rhinosinusitis with nasal polyposis (CRSwNP). METHOD: To survey and evaluate 60 cases of RESS patients (treatment group) and 120 normal ones with physical examination (Control group) through the medical outcomes survey short form questions (MOS SF-36) and the Sino-Nasal Outcome Test-20 (SNOT-20), and comparison and analysis of the two groups results which we got were carried out. RESULT: With SF-36 scales for evaluation of quality of life, the results show that: the scores of CRSwNP patients (treatment group) without surgical treatments with RESS were significantly lower than that of the control group(P < 0.05); while use of SNOT-20 scales in evaluation of the preoperative treatment group patients, the results were significantly higher than that of the control group (P < 0.05). While the CRSwNP patients with surgical treatments with RESS for 6 months, not only with SF-36 scales but also with SNOT 20 scales, there was no significant difference between the two groups (P > 0.05). CONCLUSION: RESS may obviously improve the clinical symptom of CRSNP patients. The SF-36 and SNOT-20 assessment scales could reflect the patient's QoL change. PMID- 20306854 TI - [Clinical analysis of orbital apex syndrome caused by sinus diseases]. AB - OBJECTIVE: To investigate the clinical characters and therapeutic methods of orbital apex syndrome caused by sinus diseases. METHOD: Six cases of orbital apex syndrome originated from sinus diseases were retrospective analyzed in our hospital from August 2003 to February 2009. Different therapeutic methods were taken according to different causes of disease. RESULT: Four cases of sinus infection,one cases of sphenoethmoidal mucocele, one cases of sinus squamous cell carcinoma. The results of patients with orbital apex syndrome included cure and effectiveness in 2 cases respectively, death from myocardial infarction in one case, and one case is still following up. CONCLUSION: Orbital apex syndrome originated from sinus diseases was rare, which was mainly caused by sinus infection. The key point is the correct etiology diagnosis in early phase. Treatment with endoscopic sinus surgery early is a good effective method for orbital apex syndrome caused by sinus diseases, in the same time with enough dosage of antibiotic and glucocorticoid therapy intravenously. PMID- 20306855 TI - [Studying on patient's nasal cycle of OSAHS with acoustic rhinometry]. AB - OBJECTIVE: To study the effect of OSAHS on adult nasal-cycle. METHOD: The nasal cycle of 20 healthy adults, 18 patients of snoring and 22 patients of OSAHS were examined with acoustic rhinometry, which was performed every 30 minutes in 7 hours. RESULT: The ratio of nasal cycle in healthy adults was (19/20, 95.0%), in snoring patients was (15/18, 83.0%), in patients of OSAHS was (15/22, 68.2%). The mean alteration amplitude of nasal cycle in healthy adults was significantly larger than that in patients with OSAHS (P < 0.05). The distribution of the healthy adults and patients with OSAHS between the typical cycle categories was significantly different (P < 0.05). CONCLUSION: The characteristics of nasal cycle in of OSAHS patients were different with healthy adults, which maybe owing to change of physical function of basal cavity. PMID- 20306856 TI - [Clinic analysis of cerebrospinal rhinorrhea in 24 cases]. AB - OBJECTIVE: To discuss the clinical experience of diagnosing and managing of cerebrospinal fluid (CSF) rhinorrhea. METHOD: Twenty-four cases of cerebrospinal rhinorrhea were analysed retrospectively from Jan 2003 to Sept 2008, among which 18 cases from department of Otolaryngology Head and Neck Surgery and 6 cases from Neurosurgery. RESULT: Postoperative follow-up lasted from 4 months to 72 months. All the cases were successfully cured, among which 6 cases with conservative treatment and 18 cases under surgery, and no relapse case was found. The 18 cases under surgery included endoscopic approach (12 cases), extra-nasal approach (4 cases), transnasal approach under microscope (2 cases). CONCLUSION: It is not only minimally invasive, safety and efficiency of transnasal endoscopic technique for CSF leaks, but also without facial scarring after operation. Transnasal endoscopic approach can be preferred for the closure of uncomplicated CSF leak, located at the cribriform plate or the sphenoid sinus. The extra-nasal or intracranial approach may be an attractive option for more complicated and large CSF leak, or the leak site is not easily found with endoscopic. PMID- 20306857 TI - [Bilateral versus unilateral sudden sensorineural hearing loss]. AB - OBJECTIVE: To analyze the clinical characteristics and treatment effect between bilateral (bi-) and unilateral (uni-) sudden sensorineural hearing loss (SSNHL). METHOD: Four hundred and eighty cases of SSNHL were retrospective study, which were divided into two groups of bi-SSNHL (n = 40) and uni-SSNHL (n = 440). Clinical characteristics and treatment effects were compared of the two groups. RESULT: The incidence rate of bi-SSNHL was 8.3 percent and uni-SSNHL was 91.7 percent of all patients with SSNHL. Bi-SSNHL occurs more commonly in patients of old age, diabetes mellitus, and lipid panes abnormalities compared to uni-SSNHL. Twenty-eight ears in the bi-SSNHL group showed hearing recovery (35%), compared with 56.4 percent of patients with uni-SSNHL. CONCLUSION: Bi-SSNHL and uni-SSNHL may have a completely different clinical characteristics and treatment effect, that implies a different pathophysiology and prognosis. Recognition their different clinical characteristics and treatment effect between bilateral and unilateral SSNHL can help in counseling and managing the patients and correctly evaluate the prognosis. PMID- 20306858 TI - First of her kind--filling the gap in more ways than one. PMID- 20306859 TI - Acrylic partial dentures--interim or permanent prostheses? AB - An acrylic partial denture (APD) is one option for replacing missing teeth and is also the most cost effective treatment option. Dentists are faced with the demand for replacing missing teeth from patients with limited financial resources; therefore the replacement of missingteeth with an APD is a common occurrence. One of the disadvantages of APD's is its poor strength. Dentists and dental technicians tend to design and construct acrylic partial dentures with little or no tooth support. This can have a detrimental effect on the surrounding hard as well as soft tissue. This article argues that APD's can be considered as a permanent prosthesis, provided that proper patient selection, education and the principles of partial denture design are adhered to. PMID- 20306860 TI - Compliance with preventive care following dental treatment of children under general anaesthesia. AB - OBJECTIVE: This study evaluated the self-reported preventive dental care compliance of parents/families whose children received dental treatment under general anaesthesia. STUDY DESIGN: Complete records of 68 pediatric patients who attended the University of Stellenbosch's Paediatric Dentistry Department for dental treatment were included in the survey. Parents of 41 (60%) patients were interviewed telephonically to evaluate parental dental health knowledge and preventive practices. RESULTS: The majority (85%) of parents had a good idea about the aetiology of dental caries. An assessment of the children's dental health behaviour reveals that parents were mostly responsible for brushing the childs' teeth (44%).The majority of parents (51%) reported that following dental treatment of the child under general anaesthesia, there was no change in their child's frequency of sugar consumption. Sixty-three percent of children treated under GA had returned for the one-week follow-up. However, only 22% of children returned for the three-month follow up appointment. Parents were informed about the importance of these follow-up appointments. CONCLUSION: Parental belief that proper dental health behaviour helps maintain the teeth, did not influence parents preventive compliance, despite them having received preventive instruction. Parents were mostly responsible for brushing their child's teeth following dental treatment of their children under general anaesthesia. This research found however that, in the majority of cases there was no change in the children's frequency of sugar intake. PMID- 20306861 TI - Cranio-maxillofacial surgery and rehabilitation and the University of the Western Cape. PMID- 20306862 TI - University of the Western Cape Faculty of Dentistry--and the Phelophepa health train. PMID- 20306863 TI - Comparing the performance of storage phosphor plate and Insight film images for the detection of proximal caries depth. AB - OBJECTIVES: To compare proximal caries depth between conventional film images, unenhanced and enhanced storage phosphor plate images. METHOD: Bitewing radiographs were taken on 100 patients presenting for Conservative and Periodontal treatment. Only one bitewing was taken on a patient either the right or left hand side of the patient A DenOptics storage phosphor plate and size 3 Kodak Insight film were simultaneously placed into a Rinn bitewing holder. The Insight film was placed behind the phosphor plate. Both were simultaneously exposed to radiation. The unenhanced phosphor plate images were copied four times. Contrast and brightness were either increased or decreased on the copied images. A five point scale was chosen for proximal caries depth: 0--sound, 1- caries in enamel, 2--caries reaching dentino-enamel junction, 3--caries into dentine, 4--caries in a restored area. The bitewing images were evaluated by 4 clinicians. Images with technical errors were excluded from the study. RESULTS: Altogether 1848 tooth surfaces were evaluated of which 136 surfaces were excluded due to technical errors. The results show that for the detection of proximal caries there is no significant difference in accuracy between unenhanced storage phosphor plate and Kodak Insight film images (p > 0.001). When decreasing both contrast and brightness there was no significant difference in diagnostic accuracy (p > 0.001) between unenhanced and enhanced storage phosphor plate images. More surfaces were analyzed for caries into the dentine on the enhanced images when both contrast and brightness were increased. CONCLUSION: Although contrast-enhanced and brightness-enhanced images retween conventional film, unenhanced and enhanced images. PMID- 20306864 TI - Areca nut and tobacco chewing habits in Durban, KwaZulu Natal. AB - Areca nut/quid chewing is a habit that is commonly practiced in the Indian subcontinent and this age-old social habit is still being practiced by the Indians in South Africa. The areca nut/quid is prepared in a variety of ways. The quid may be prepared with or without tobacco. This habit is said to be associated with the development of oral submucous fibrosis (OSF), a premalignant lesion, oral leukoplakia and oral cancer. The aim of the present study was to investigate the prevalence of areca nut/quid chewing (with or without tobacco), associated habits (smoking and alcohol consumption) as well as the awareness of the risks. The study was cross-sectional in design and used administered questionnaires and semi-structured interviews to collect the data. A convenience sample of 101 respondents was interviewed. More than three quarter were born in South Africa and the rest were migrant communities from Pakistan, India and Dubai. All respondents from the migrant community were males. Slightly more females than maleschewed areca nut/quid. Popular ingredients that were chewed included areca nut, betel leaf, lime and paan masala. Enjoyment and special functions were the most important reasons for chewing areca nut. Family influence was a reason for chewing. Nearly 60% did not know whether areca nut chewing is harmful to their health. The majority have not attempted to give up the habit. It is recommended that aggressive awareness programmes on the hazardous effects of areca nut/quid chewing be developed similar to those for smoking cessation. Government health warnings need to be written on paan packaging. Taxes need to be imposed on the areca nut and condiments. Age restrictions need to be imposed on purchasing of the areca nut/quid thus making access difficult for the children. PMID- 20306865 TI - Oral mucosal lesions and HIV status in a rural household survey in South Africa. AB - Several studies have documented the relevance of oral lesions in HIV populations. Oral HIV lesions are also considered useful indicators in HIV therapy. The objectives of the present study were to determine the prevalence of oral mucosal lesions (OML) in a rural population and to determine the differences, if any, in the prevalence of oral mucosal lesions of persons infected with HIV and persons not infected with HIV. The study was part of the Vaccine Preparedness Study (VPS) conducted by the Medical Research Council in Hlabisa, KwaZulu Natal, South Africa between 2000 and 2002. METHODS: A cross-sectional household survey examined adults aged 15 to 50 years. Oral mucosal lesions were determined by a presumptive diagnosis. Informed consent was obtained for the oral examination and separately for collecting a blood sample to determine HIV status by ELISA. RESULTS: A total of 2313 adults were interviewed for the VPS. Oral mucosal lesions were assessed in a sample comprising 537 adults. Of these, 185 consented to HIV testing and 22.7% (95% Confidence Interval (CI): 16.9-29.4%) were HIV positive. The prevalence of oral mucosal lesions in the total sample was 12.8% (95% CI: 10 16.3%). The prevalence of OML was 21.4% (9/42) among those who consented to a blood test and were HIV positive and 9.8% (n = 14/143) among those who were HIV negative. CONCLUSION: The prevalence of OML among HIV positive participants was significantly higher than among HIV negative participants. PMID- 20306866 TI - Association between periodontitis and systemic inflammation in patients with end stage renal disease. AB - Patients with end-stage renal disease (ESRD) experience a significantly increased rate of atherosclerotic complications. Inflammation plays a central role in the pathogenesis of these complications and C-reactive protein (CRP) has been found to be predictive of all-cause and cardiovascular mortality. Many patients have elevated CRP levels without an apparent infection. Periodontal diseases in the general population have been associated with both an increased prevalence of atherosclerotic complications and an elevation in serum CRP values. This study examined the association between periodontal disease and elevated CRP in patients with ESRD on chronic dialysis. METHODS: Eighty patients on chronic dialysis were included in the study. Demographic information, medical history and CRP levels were recorded. Periodontal examination was carried out by a single calibrated examiner and included gingival index (GI), bleeding on probing (BoP), probing depths (PD) and clinical attachment loss (CAL). These measurements were recorded in relation to the Ramfjord teeth. The presence in any one sextant of PD > or =4 mm or clinical loss of attachment > or =3 mm was diagnosed as periodontitis. RESULTS: Mean age of subjects was 50.3 +/- 9.06 years with a median time on dialysis of 24 months. 57.5% (n=46) of subjects were diagnosed as having periodontitis; of these 52.2% had CRP levels >10 mg/l. Of the 34 subjects with healthy periodontium, only 10 (29.4%) had elevated CRP levels. The serum CRP levels between these two groups were significantly different (p = 0.004). CONCLUSION: The results of the study showed significantly elevated levels of CRP in ESRD patients with periodontitis. Periodontal diseases may be an overlooked source of inflammation in ESRD patients. PMID- 20306867 TI - Effect of various tooth-whitening products on enamel microhardness. AB - OBJECTIVES: The purpose of this in vitro study was to evaluate the effect of various tooth-whitening products containing carbamide peroxide (CP) or hydrogen peroxide (HP), on enamel microhardness. METHODS: Enamel blocks were exposed to: Nite White ACP 10% CP (Group 2, n=10); Yotuel Patient 10% CP (Group 3, n=10); Opalescence PF 10% CP (Group 4, n=10); Opalescence PF 20% CP (Group 5, n=10); Opalescence Treswhite Supreme 10% HP (Group 6, n=10); Yotuel 10 Minutes 30% CP (Group 7, n=10); Opalescence Quick 45% CP (Group 8, n=10), Yotuel Special 35% HP (Group 9, n=10), Opalescence Boost 38% HP (Group 10, n=10) according to the instructions of the manufacturers. The control (Group 1, n=10) was enamel blocks kept in artificial saliva at 37 degrees C without any treatment. The microhardness values were obtained before exposure and after a 14-day treatment period. Specimens were kept in artificial saliva at 37 degrees C between treatments. Data were analysed using Kruskal-Wallis one-way ANOVA and Tukey Kramer Multiple Comparison Test. Indent marks on the enamel blocks were also examined under the Scanning Electron Microscope. RESULTS: All whitening products decreased enamel microhardness except group 10 but only Groups 2, 3, 4, 5 and 7 showed significant decrease in enamel microhardness as compared to the control group (p < 0.05). Groups 2, 3 and 7 differed significantly from all the other groups (p < 0.05). The highest damage was recorded for Group 2 (Nite White ACP 10% CP), which differed significantly from Groups 3 and 7. SEM images also showed damage to enamel. CONCLUSIONS: All products tested in this study decreased enamel microhardness except Opalescence Boost 38% HP. The products containing carbamide peroxide were more damaging to enamel because of the longer application times. Nite White ACP 10% CP showed the highest reduction in enamel microhardness as compared to other products tested. PMID- 20306868 TI - The mixed dentition pantomogram: a valuable dental development assessment tool for the dentist. AB - The mixed dentition pantomogram is routinely used in paediatric patients. This paper discusses the value of the pantomogram for early identification of problems in dental development during the mixed dentition stage. Aspects regarding dental maturity, leeway space, the sequence of eruption of the permanent teeth, anomalies and the development of the canines will be reviewed. PMID- 20306869 TI - Microleakage of four composite resin systems in class II restorations. AB - OBJECTIVE: To compare the microleakage at the enamel and dentine/cementum margins of three nanocomposites and a microhybrid composite in Class II restorations. MATERIALS AND METHODS: Four light-cured dental resin restorative materials in combination with their respective bonding agents were investigated. Eighty non carious, extracted human molars were divided into 4 groups of 20 teeth each. The apices of the teeth were sealed with a resin modified glass ionomer cement. Standardized Class II slot cavities were prepared on the proximal surfaces of each tooth. Each group had an equal number of cavities with gingival margins on enamel and on dentine/cementum. Restorations were placed as indicated: Group 1 (G1): Ceram-X mono/Prime & Bond NT (Dentsply), G2: Premise/ OptiBond Solo Plus (Kerr), G3: Grandio/Admira Bond (VOCO), G4: Z100/Adper Scotchbond Multi-Purpose (3M ESPE). After thermocycling and immersion in 0.5% methylene blue dye solution, the teeth were sectioned and dye penetration was scored on a scale of 0 to 3 on both the enamel and dentine/cementum margins. The data were analyzed using a Kruskal-Wallis one way ANOVA and Mann-Whitney U test of ranks (significance at p < 0.05). RESULTS: In the enamel group: Z100/Adper Scotchbond Multi-Purpose showed significantly higher leakage when compared to the other three groups (p < 0.05). In the dentine/cementum group: Grandio/Admira Bond showed significantly lower microleakage when compared to the other materials tested while Z100/Adper Scotchbond Multi-Purpose showed the largest microleakage (p < 0.05). CONCLUSION: No material was able to eliminate microleakage completely at the dentine/cementum margin with Grandio/Admira Bond showing the least microleakage when compared to the other three materials tested. At the enamel margins, all materials tested performed reasonably well. PMID- 20306870 TI - General practitioner's radiology case 79. Albers-Schonberg disease (osteopetrosis -marble bone). PMID- 20306871 TI - Oral medicine case book 23. Case 1--snuff dipper's lesion, Case 2--nicotinic stomatitis. PMID- 20306872 TI - Featuring dental education research: applying the principles of action research to improve teaching of dental prosthetics. AB - This article focuses on educational research conducted at the newly merged UWC faculty of dentistry. The research emphasises the change in teaching methods employed to address the concerns experienced in teaching the new large classes as observed in the prosthetic techniques module. These educational interventions were conducted over 5 years and the study design included the principles of action research. Students were assisted in learning the theory of the practical procedures and the subsequent completion of these procedures with the accurate application of the theoretical concepts. Changes in the teaching methods enhanced students learning and successful translation of the theory into practical work. The active learning exercises incorporated into the teaching further motivated and assisted students with deep learning. The debates indicated that students know and accept the value of the module as part of their training. PMID- 20306873 TI - Supporting nursing residency programs. PMID- 20306874 TI - The diabetes disease state management exemplar. AB - One relatively new method of providing care to patients with chronic disease is disease state management (DSM). Diabetes is particularly interesting to study because it is not only one of the most prevalent chronic diseases, but it is also a disease for which DSM is highly cost effective. Similarly, registered nurses represent the group of practitioners most likely to provide a comprehensive set of DSM activities. This experiment was conducted in fall 2005 at a nationally recognized diabetes center which is affiliated with a large, full service medical center. The results suggest at least three forms of content delivery--in-class, at-home study packets, and online modules--are all equally effective at enhancing diabetes DSM knowledge. PMID- 20306875 TI - Characteristics of internationally educated nurses in the United States: an update from the 2004 National Sample Survey of Registered Nurses. AB - Internationally educated nurses (IENs) have become an integral part of the U.S. registered nurse workforce. To understand the U.S. RN workforce and conduct nurse workforce planning, it is fundamental to know the who, what, and where about IENs. Analysis of the 2004 National Sample Survey of Registered Nurses revealed demographic and employment characteristics of IENs practicing in the United States. The results can help employers, recruiters, and policymakers stay abreast of the changing profile of IENs in order to make informed decisions regarding the recruitment of lENs, and U.S. workforce planning and policy. More importantly, systematic actions such as developing tailored transitional programs should be implemented to better integrate and retain IENs who are playing an increasingly important role of caring for Americans. PMID- 20306876 TI - Key elements of large survey data sets. AB - One low-cost area of research that nurses typically do not consider is to perform secondary analyses of large federal or state health care data sets. These data sets contain vast amounts of existing data that otherwise would be difficult and expensive to gather, thereby enabling research which is economically feasible and which potentially has wide implications and applications. Large survey data may be free and easy to access, but that does not mean that retrieving the raw data, examining the manuals for the survey, and conducting the secondary analysis is simple or easy. To analyze the data accurately, it is essential that nurse researchers fully understand all key elements of the data set survey chosen, as well as how to prepare and manage the data. In a time of limited funding and resources, and of numerous health concerns in all age groups across different races and ethnicities, nurse researchers need to utilize the many venues that contain rich and vast amounts of data such as large data sets. PMID- 20306877 TI - Nursing workload measurement in ambulatory care. AB - The scarcity of ambulatory workload tools has led many institutions to use metrics such as the number of physicians, patient panels, scheduled patient visits, procedure volumes, seasonality, etc. to determine staffing levels. These metrics do not accurately reflect the nurse staffing required to support the practice. The Workload Measurement and Reporting System (WMRS) was designed to meet the need of measuring work and collecting ambulatory nurse workload data at the point of care in diverse ambulatory practices. The pilot test confirmed that the WMRS application was successful in capturing workload in ambulatory practices that participated. While this method for measuring ambulatory nurse work required time and effort from the clinician, the WMRS application collected and stored a vast amount of valuable workload data when used consistently. PMID- 20306878 TI - Expanding the role of nursing in health care governance. AB - Nurses are an untapped resource for health care governing boards. It is essential to help nurses fulfill their potential to competently and confidently participate in the governance of our nation's health care organizations. Understanding the health care governance landscape is an important first step for nurses to take on the path to pursuing board service. Like other professionals who seek to more fully prepare themselves to take on the unique challenges of governance, nurses also have access to a range of resources such as Best On Board, a new education, testing, and certification program. Best On Board offers a continuum of courses designed to help both new and seasoned trustees demonstrate their understanding of board issues and responsibilities, enabling them to quickly and confidently contribute in their governance role. PMID- 20306879 TI - Sensible compromise: will there be health care reform? AB - Three significant challenges to the passage of health care legislation bear watching as they have the potential to make sensible compromise between the House and Senate unlikely. The first threat is the continuing exposure of the public to misinformation from media commentary and interest groups. If health care delivery issues weren't complex enough, another growing issue is the misuse of the filibuster, further obscuring change and clarity in legislative discussion. The third threat is a move by opponents of current health care reform to engage the Supreme Court and challenge the constitutionality of the legislation. If substantive health reform legislation fails to pass, nursing will have received a deep wound along with the rest of this country. Our voice as patient advocates must be stronger in these final days. PMID- 20306880 TI - Health care payment reform: implications for nurses. PMID- 20306881 TI - The human side of staffing. AB - While the call for data-driven staffing is loud and even overdue, our approach to it must be harmonized with the human side as well. Discovering the right combination of hard data and soft data may well be the impetus needed to catapult a shift in how we approach staffing to new levels of effectiveness. Nurses should not be apologizing for our focus on quality and the patient experience, but rather leveraging the human understanding that nursing has mastered into our business models, financial plans, and staffing programs. The way human beings respond to something, no matter how grounded in scientific facts and evidence, can mean effectiveness or ineffectiveness, success or failure. In developing staffing strategies, programs, and practices, it can be helpful to consider the "experience impact" as part of the decision-making process. PMID- 20306882 TI - Development of the role of director of advanced practice nursing. AB - Advanced practice nurses (APNs) are integral to cost-effective delivery of health care in large health care organizations. Development of the leadership position of director of advanced practice nurses in a large teaching institution provides leadership to APNs in various settings, contributes to staff satisfaction, facilitates increased professional growth, and provides improved quality and fiscal outcomes. Job satisfaction, productivity, accountability, and communication may be enhanced through implementation of the role of director of advanced practice nursing and a committee structure of APNs, as was found in this academic health system. PMID- 20306883 TI - Tilt training and pacing: a report on 9 patients with neurally mediated syncope. AB - OBJECTIVE: In patients with neurally mediated syncope (NMS), pacing has been used to prevent bradycardia and syncope. However, recurrence due to the vasodepressor component remains a problem. METHODS: We report on tilt training in 9 patients with a pacemaker (PM) implantation. Patients were submitted to daily in-hospital tilt testing. They were instructed to continue this therapy at home. RESULTS: A negative tilt test was obtained in all patients. Six patients remained free from syncope. Recurrent syncope was observed in 3 patients. In 4 patients the pacemaker had been implanted before the start of the tilt training programme. Five patients had a pacemaker implanted after the administration of tilt training therapy. CONCLUSION: NMS also occurs in paced patients.Tilt training improves the clinical outcome by restoring the vasoconstrictor reserve capacity. PMID- 20306884 TI - Dilated cardiomyopathy, spontaneous echo contrast in the aorta and embolic events. AB - BACKGROUND: Spontaneous echocardiographic contrast (SEC) is a frequent finding in patients with dilated cardiomyopathy (DCM). In this study, we have investigated the frequency and clinical correlates of aortic-SEC (Ao-SEC) in patients with DCM. METHODS: Ninety-two consecutive DCM patients (63 men, 29 women, mean age 60 +/- 11 years) underwent transthoracic and transoesophageal echocardiography. RESULTS: Ao-SEC was found in 53 patients (58%). It was associated with: (i) a lower cardiac index (P < 0.001); (ii) left atrial-SEC (P < 0.001); (iii) left ventricular-SEC (P = 0.008); (iv) a larger aortic root (P = 0.02); (v) the presence of complex aortic atherosclerotic plaques (P < 0.001).The significant determinant of thromboembolism was left-atrial SEC (P = 0.03).We did not find a significant correlation between Ao-SEC and thromboembolism. CONCLUSION: Most of the patients who developed embolic events in the follow-up period had Ao SEC.Thromboembolism is rather associated with left-atrial SEC than with Ao-SEC. PMID- 20306885 TI - Mechanistic insights into initiation and maintenance of ventricular fibrillation: implications for catheter ablation. AB - OBJECTIVE: This report is intended to provide an overview of the mechanism(s) of ventricular fibrillation (VF) and its relation to catheter ablation. METHODS AND RESULT: We conducted a Pubmed and Medline literature search to identify all experimental and clinical studies published in English involving the mechanisms of VF and catheter ablation for VF. We found that controversies still exist with respect to the initiation and maintenance of VF despite more than a century of research due to the complexity of this arrhythmia and the limitation of the mapping technology. However, catheter ablation targeting the triggering factor for VF has been successfully applied in some patients who experience failure of drug therapy and frequent implanted cardiac defibrillator shocks. CONCLUSIONS: VF is frequently triggered by short-coupled monophasic ventricular premature beats. VF is characteristic of partial and temporal organization instead of a state of completely aperiodic and disordered activation. Catheter ablation targeting the triggers for VF seems to be a safe and effective means for preventing VF in some patients. PMID- 20306886 TI - Valsartan alleviates atherosclerotic lesions in pulmonary arteries of rabbits via an endothelium-dependent mechanism. AB - OBJECTIVE: Angiotensin II plays an important role in the pathogenesis of atherosclerosis. This study was designed to examine the effect of valsartan, an angiotensin receptor blocker, on atherosclerotic lesions in pulmonary arteries of rabbits with atherosclerosis induced by a high-cholesterol (HC) diet. METHODS: Male New Zealand rabbits were randomly divided into four groups: control, HC without valsartan, HC with 3 mg/kg/d valsartan, and HC with 10 mg/kg/d valsartan. Following 12 weeks of treatment, serum lipid profiles were determined. Pulmonary arteries were harvested and stained with Sudan IV for evaluation of atherosclerotic lesions. The middle lobes of the rabbit lungs were isolated, embedded in paraffin, and sectioned and stained with haematoxylin and eosin. Nitric oxide (NO) and endothelin-1 (ET-1) levels were determined in pulmonary arteries by nitrate reductase assay and radioimmunoassay, respectively. RESULTS: HC feeding altered serum lipid levels and induced atherosclerotic lesions in pulmonary arteries. Although 12 weeks of valsartan treatment failed to alter serum lipid levels, it significantly ameliorated HC-induced atherosclerotic lesions. Lesion areas, inflammatory cell infiltration, and occlusions of small arteries of lungs were reduced. Moreover, the endothelium-derived NO levels in pulmonary arteries were increased by valsartan treatment (10 mg/kg/d) compared to levels in the HC group. ET-1 levels were decreased by valsartan treatment compared to levels in the HC group. NO and ET-1 levels were not altered by valsartan at 3 mg/kg/d. CONCLUSION: Our data demonstrates that HC diet-induced atherosclerotic lesions in rabbit pulmonary arteries can be ameliorated by treatment with valsartan, possibly through a NO and ET-1-dependent mechanism. PMID- 20306887 TI - Influence of drug-eluting stent on inflammation during restenosis in a porcine coronary model. AB - OBJECTIVE: The aim of this study is to compare anti-inflammatory and intimal hyperplasia inhibiting efficacy between the Firebird rapamycin drug-eluting stent and a bare metal stent in a porcine coronary injury model. METHODS: Twelve rapamycin drug-eluting stents (Firebird), and 12 bare metal stents (BMS) were deployed with the oversizing method into porcine coronary arteries. Coronary angiography, histopathological and immunocytochemistry analysis were carried out at week 4 after stenting. RESULTS: The distribution of stented vessels, diameter of reference vessels, and post-procedural minimal lumen diameter were compared between the two groups. At week 4 of follow-up, quantitative coronary angiography (QCA) showed that the minimal lumen diameter and late lumen loss were greater, and percent stenosis was less in the Firebird stent group than in the bare metal stent group. In the histopathological analysis, compared to the BMS group, injury score in the Firebird stent group (1.87 +/- 0.16 vs. 1.32 +/- 0.13) and inflammation score (1.86 +/- 0.55 vs. 1.12 +/- 0.35) decreased, P < 0.05. There are significant differences for neointimal area (4.60 +/- 1.39 mm2 in the BMS group vs. 1.51 +/- 0.45 mm2 in the TCS group, P < 0.05). The lumen area in the Firebird stent group enlarged (3.24 +/- 0.93 mm2 in the BMS group vs. 4.34 +/- 0.93 mm2 in the Firebird stent group, P < 0.05). Immunohistochemistry revealed that the Firebird stent suppressed cell proliferation (Ki67) and expression of nuclear factor-kappaB (NF-kappaB) in the arterial wall. CONCLUSION: The Firebird stent showed suppression of constrictive remodelling, inhibition of neointimal hyperplasia through antiproliferation, and anti-inflammation acts via attenuated NF-KB activation, which has proved to be a feasible method for preventing restenosis after coronary angioplasty in pigs. PMID- 20306888 TI - Prevalence of preoperative arrhythmias in children with delayed treatment of severe congenital heart disease. AB - AIM: Our aim was to determine the real importance of rhythm and conduction disorders in children with unoperated severe congenital heart disease. METHODS: Consecutive children with delayed treatment of severe congenital heart disease were prospectively studied for the occurrence of arrhythmias before any invasive investigation or surgical procedure was performed. RESULTS: All 168 children were in sinus rhythm. One hundred and fifty-eight patients (94%) had no significant preoperative findings. One child with double discordance had an intermittent complete atrioventricular block, and another one had a long QT syndrome. Children with severe ventricular dysfunction had paroxysmal atrioventricular re-entry tachycardia in 3 cases and abnormally frequent premature ventricular complexes in 3 other cases. Children with severe left atrial dilatation had periods of atrial ectopic tachycardia in one case and atrial fibrillation in another case. CONCLUSIONS: The prevalence of rhythm and conduction disorders is relatively low in children with delayed treatment of severe congenital heart disease. Only those with congenital heart disease classically combined with such disorders and those with prolonged severe ventricular dysfunction and/or atrial dilatation are at risk of developing significant arrhythmias and should undergo a preoperative assessment of arrhythmias. PMID- 20306889 TI - Usefulness of 6-minute walk test, plasma neurohumoral and cytokine activation in the assessment of symptomatic patients with left ventricle dysfunction caused by chronic severe mitral valve regurgitation. AB - OBJECTIVE: The aim of our study was to select the most relevant markers of impaired left ventricle (LV) function in patients with heart failure (HF) symptoms due to severe chronic mitral regurgitation (MR). METHODS AND RESULTS: Thirty-six patients with decompensated HF due to severe MR underwent echocardiography, 6-minute walk test (6MWT) and measurements of plasma renin activity, angiotensin II, aldosterone, noradrenaline (NA), brain natriuretic peptide (BNP), tumour necrosis factor alpha (TNFalpha) with its receptors, and interleukine-6. Patients presented with significant neurohumoral/cytokine activation. By stepwise multiple regression analysis the strongest prediction model for 6MWT included LVEDVI (R2 = 0.95, P = 0.024), BNP (R2 = 0.67, P = 0.0006), IL-6 (R2 = 0.90, P = 0.044); for BNP: 6MWT (R2 = 0.36, P = 0.003), LA (R2 = 0.56, P = 0.0077), LVESVI (R2 = 0.83, P = 0.0072); for NA: EF (R2 = 0.4 1, P = 0.036), and for TNFalpha: LVESVI (R2 = 0.65, P = 0.003). CONCLUSIONS: 6MWT and neurohumoral markers (mainly BNP, but also NA and TNFalpha) are good predictors of the degree of LV remodelling, showing an independent correlation with the level of LV dilatation/dysfunction in chronic severe MR.These assessments may supplement standard echocardiography in LV decompensation due to severe MR. PMID- 20306890 TI - Investigation of oxidant and antioxidant pathway changes in acute rheumatic fever. AB - AIM: The purpose of this study was to investigate the role of oxidant stress in the clinical process and pathogenesis of acute rheumatic fever (ARF). MATERIAL AND METHODS: The study included 33 children with ARF and 20 healthy control subjects. The diagnosis of ARF was established according to the Jones Criteria. Malondialdehyde (MDA), reduced glutathione (GSH), alpha-tocopherol, ascorbic acid, retinol and beta-carotene levels were measured as markers of oxidative stress together with some antioxidant markers. RESULTS: Our study includes 33 (19 male, 14 female) children with ARF and 20 (11 male, 9 female) healthy control subjects. The mean age ranged between 5-16 years and 5-15 years in the study and control groups, respectively. MDA was measured as 2.1 +/- 0.9 nmol/mL in the control group, 3.3 +/- 2.7 nmol/mL in the study group before treatment, and 2.1 +/- 1.2 nmol/mL after treatment. Blood GSH levels were 48.2 +/- 12.7 mg/dL in the control group, 24.7 +/- 16 mg/dL in the study group before treatment, and 40.6 +/ 21.3 mg/dL in the study group after treatment. MDA and GSH levels prior to the treatment were found to be significantly high and low as compared with the levels of the control group, respectively (P < 0.05, P < 0.001). After treatment, statistically important decrements and increments were determined in the levels of MDA (P < 0.05) and GSH (P < 0.01), respectively. Furthermore, alpha tocopherol, retinol and beta-carotene levels prior to treatment in the study group, were significantly lower in comparison with control group levels (P = 0.05, P < 0.05, P < 0.01, respectively). CONCLUSION: We suggested that tissue damage in ARF may not only occur in the presence of increased oxidative stress, but also as a consequence of decreased antioxidant markers. PMID- 20306891 TI - Carotid intima-media thickness: more than a research tool? AB - Carotid intima-media thickness (CIMT) can be measured non-invasively by means of B-mode ultrasound. Carotid ultrasonography is readily available and enables the assessment of the full spectrum of the atherosclerotic process, from normal artery walls to arterial occlusion. In population studies, CIMT correlates with present and future cardiovascular disease (CVD). The method has been well validated in histological and epidemiological studies. Controlled clinical trials have shown the value of CIMT as a surrogate marker to evaluate established therapies and novel anti-atherosclerotic drugs. At present, CIMT is increasingly being used as a surrogate aimed at reducing CVD risk at an individual level. In this paper we discuss the potential usefulness of CIMT as a risk marker in clinical programmes of CVD prevention. PMID- 20306892 TI - The right ventricle: anatomy, physiology and functional assessment. AB - Right ventricular function is acknowledged as an important prognostic element in cardiovascular pathologies. Although recent years have seen significant advances in the exploration of cardiac function, assessing right ventricular performance still remains a challenge for the daily practice. The right ventricle is a complex structure that cannot be approximated by a simple geometric form. It functions in a low impedance system therefore it is sensitive to pressure overload. Along with contractility and loading conditions, ventricular interactions play an important part in right ventricular function and failure. The aims of our review are to describe the main characteristics of RV anatomy, function and failure and also to present the standard and novel tools that can be employed to investigate them. Moreover, the advantages, limitations and clinical significance of each parameter will be discussed. PMID- 20306893 TI - Contribution of contrast echocardiography to the differentiation between a thrombus and a tumorous mass in end-stage lung carcinoma. PMID- 20306894 TI - Left atrial appendage occlusion using an amplatzer cardiac plug. PMID- 20306895 TI - Sarcoidosis: an unusual cause of acute pericarditis. AB - Mild to moderate asymptomatic pericardial effusions are commonly detected in patients with biopsy-proven sarcoidosis. However, symptomatic pericarditis is rare during the course of the disease. All reported cases at presentation were life-threatening tamponades. We describe the first case of a patient in whom sarcoidosis was revealed by an acute benign pericarditis persisting despite administration of colchicine and non-steroidal anti-inflammatory drugs. Similar cases may have been ignored since the initial diagnosis of sarcoidosis is challenging and corticosteroids are frequently given to patients with persistent chest pain. Clinicians should consider the possibility of sarcoidosis in case of pericarditis resistant to first-line therapy. PMID- 20306896 TI - Malignant fibrous histiocytoma of the heart: a case report. AB - Malignant fibrous histiocytoma (MFH) in the heart is rare. We present a case of a 38-year-old woman with histologically confirmed MFHs in the left atrium, liver and bone. The patient presented with shortness of breath and right shoulder pain. A plain radiograph showed an osteolytic lesion at the neck of the humerus on the right side. A computed tomography (CT) scan of the chest showed a lobulated tumour occupying the cardiac left atrium and a large heterogeneously enhancing mass in the liver and osteolytic metastasis in the thoracic spine. The patient underwent complete resection of the cardiac tumour, and histology showed a high grade pleomorphic sarcoma--an MFH. Biopsy of the lesions on the right shoulder and in the liver also showed the same histologic diagnosis. PMID- 20306897 TI - Percutaneous pulmonary valvuloplasty and atrial septal defect closure in a 69 year-old patient with Noonan's syndrome. AB - We present the case of a patient with Noonan syndrome who was seen for the first time at the age of 69 years with combined pulmonary valve stenosis and atrial septal defect. The patient was treated by a staged percutaneous approach. The treatment of these combined congenital heart defects remains challenging because their haemodynamics interact directly. In this case report we discuss both the underlying pathophysiology and haemodynamics. PMID- 20306898 TI - Catastrophic rapid onset heparin-induced thrombocytopenia--victim of our own success. AB - Heparin is integral to the treatment of acute coronary syndromes, deep vein thrombosis and its prophylaxis. An undesirable result of recurrent heparin use is rapid onset heparin-induced thrombocytopenia (HIT) within hours of exposure. This catastrophic condition is frequently diagnosed too late for therapy to be effective. We describe a case of fatal rapid onset HIT, analyze current evidence to diagnose this condition and propose a way so that it can be prevented. PMID- 20306899 TI - Fulminant myocarditis with dramatic response to corticoids. AB - A 47-year-old healthy man developed acute fulminant coxsackie BI myocarditis with cardiogenic shock and extreme elevation of NT-pro-BNP (82585 pg/ml). He had a dramatic and rapid improvement within the following days after administration of corticoids on top of dobutamine and classic treatment. PMID- 20306900 TI - Stroke and recurrent peripheral embolism in left atrial myxoma. AB - Primary cardiac tumours are uncommon, with an estimated incidence between 0.0017% and 0.19%. Cardiac myxoma is a rare cause of cerebrovascular disease, especially in children. This case report emphasizes the importance of cardiac evaluation, especially echocardiographic examination in cases with stroke and peripheral embolism. PMID- 20306901 TI - The Society for Internet-based Scientific Studies: a new platform to promote multicentric studies in the Royal Belgian Society for Surgery. PMID- 20306902 TI - The "Internet-based Scientific Studies" project of the Royal Belgian Society for Surgery: general rules. Edition 2010. PMID- 20306904 TI - The science behind topical negative pressure therapy. AB - Topical negative pressure therapy (TNP) is an established part of modern wound healing. With an increasing choice in TNP providers, understanding the differing modes of action, the biochemical and biophysical effects on the wound at a microscopic and macroscopic level, plus the role of the interface dressings, will aid the clinician in planning a clear goal of therapy. This article reviews the scientific evidence for TNP to date and explores each mechanism of action and the implications for wound healing and patient outcomes. PMID- 20306903 TI - Analysis of surgical errors in malpractice claims in Belgium. AB - The relative importance of the different factors that cause surgical error is unknown. Malpractice claim file analysis may help to identify leading causes of surgical errors and identify opportunities for prevention. We retrospectively reviewed 427 surgical malpractice claims from 3202 malpractice liability cases in which patients alleged error between 1996 and 2006. Surgeon-reviewer examined the litigation file and medical record to determine whether and injury attributable to surgical error had occurred and, if so, what factors contributed. Detailed descriptive information concerning etiology and outcome was recorded. The reviewer identified surgical errors that resulted in patient injury in the 427 studied claims. Sixty-three percent of these cases involved significant or major injury; 6% involved death. In most cases (48%), errors occurred in intra operative care; 15% in preoperative care; 37% in postoperative care. Nine percent of the cases had errors occurring during multiple phases of care; in 28%, more than one clinician played a contributory role. System factors contributed to error in 90% of cases. The leading system factors were inexperience/lack of technical competence (57%) and communication breakdown (42%). Cases with technical errors (57%) were more likely than those without technical errors (43%) to involve elective surgery (57% vs. 60%, Fisher's Exact Test < 0.001). There were no clear contributions to error from multiple personnel (26% vs. 31%, Fisher's Exact Test 0.28) and errors in multiple phases of care (73% vs. 68%, Fisher's Exact Test 0.28). In addition technical error cases were more likely than those without technical errors to have been caused by lack of clear lines (14% vs. 21%, Fisher's Exact Test 0.03), abnormal or different anatomy (6% vs. 2%, Fisher's Exact Test 0.04), interruption or distraction (14% vs. 4%, Fisher's Exact Test < 0.001). On the other hand, they were less likely to have been caused by judgment errors (47% vs. 59%, Fisher's Exact Test < 0.001). There were significant more problems caused by the numbers of personnel involved in university hospitals than in non-university hospitals. On the other hand, they were less likely to have been caused by failure of vigilance/memory (16% vs. 58% Fisher's Exact Test < 0.001), breakdown (19% vs. 50%, Fisher's Exact Test < 0.001), lack of supervision (2% vs. 34%, Fisher's Exact Test < 0.001) and lack of clear lines (1% vs. 22%, Fisher's Exact Test < 0.001) in university hospitals than in non-university hospitals. System factors play an important role in most surgical errors, including technical errors and some non technical errors. Malpractice claims analysis could encrypt the leading areas for intervening to reduce errors. PMID- 20306905 TI - The effect of statins on perioperative events in patients undergoing vascular surgery. AB - Despite recent advancements in perioperative care and guideline recommendations, patients undergoing vascular surgery remain at risk for perioperative cardiovascular complications. In this review, the results are summarized of the most recent studies on the effectiveness and safety of perioperative statin use for the prevention of these perioperative cardiovascular complications. Perioperative statin therapy was associated with an improvement in postoperative cardiovascular outcome and a reduction in serum lipid levels and levels of inflammation markers. PMID- 20306906 TI - Palliative treatment of malignant pleural effusions. AB - AIM: The aim of the current study was to analyse the results of video assisted thoracoscopic (VATS) talc pleurodesis for malignant pleural effusion. MATERIAL AND METHODS: From January 2002 to December 2004, 50 VATS procedures were performed under general anaesthesia on 48 patients for malignant pleural effusion. There were 45 women and 3 men with a median age of 57 years. The most common primary neoplasms were breast cancer (68%), ovarian cancer (6%), colon cancer (4%) and lung cancer (4%). Five patients had other types of tumour, including malignant lymphoma, fibrosarcoma, renal cell carcinoma, malignant pleural mesothelioma, acute myeloblastic leukaemia. RESULTS: The average duration of the operation was 46 min (range 20-120). Median duration of postoperative drainage was 5 days (range 2-13) and postoperative hospitalisation was 8 days (range 2-13). Four patients had postoperative complications. Thirty-day mortality was 1/48. One patient died from myocardial infarction. Three postoperative complications were noted (one non-septic febrile episode, one bilateral pneumopathy and one transitory hypoxaemia, treated by non invasive ventilation). Patients were relieved from dyspnoea in 34/48 of the cases (71%). Median survival was 6 months (ranging from 14 days to 2 years). CONCLUSIONS: Early talc pleurodesis via VATS is a safe technique for successfully treating pleural effusion and preventing recurrence in palliative patients with a symptomatic malignant pleural effusion. PMID- 20306907 TI - Surgical strategy in patients with secondary and tertiary hyperparathyroidism. A bi-institutional series. AB - BACKGROUND: Although total parathyroidectomy with forearm autotransplantation is a widely accepted treatment for patients with secondary/tertiary hyperparathyroidism (HPT) some debate persists about the optimal surgical strategy. In particular, the question what to do when less than four parathyroid glands can be found during surgery has yet to be resolved. The aim of this retrospective study was to review the outcome of total parathyroidectomy with autotransplantation and to assess the proper procedure (to autotransplant or not) when finding less than 4 glands after extensive surgical exploration. METHODS: Between 1995 and 2005, parathyroidectomy was performed in 74 patients in two affiliated centers. In this case-control study both clinical and biochemical outcomes of a total or subtotal parathyroidectomy were compared. The parathyroid hormone (PTH), serum calcium concentration, phosphate and alkaline phosphatase levels were monitored preoperatively, 1 and 12 months postoperatively. RESULTS: Sixty five patients underwent a total parathyroidectomy and nine patients underwent a subtotal parathyroidectomy. Persistent HPT was seen in nine patients (12%). Recurrent HPT was seen in eight patients (11%). There were no significant differences between the group with > or = 4 glands excised and the group with three glands excised regarding serum PTH levels after 12 months and the number of patients with a hypo- or hyperparathyroidism (persistent or recurrent). Procedure related morbidity was minimal. CONCLUSIONS: Total parathyroidectomy with forearm autotransplantation is safe and effective for patients with secondary/tertiary hyperparathyroidism. In case of not finding a fourth gland after extensive surgical exploration, our general advice is to proceed as planned with the autotransplantation. PMID- 20306908 TI - Postoperative PTH measurement as a predictor of hypocalcaemia after thyroidectomy. AB - BACKGROUND: Hypocalcaemia after thyroidectomy is the most common postoperative complication, with a reported incidence from 0.5% to even 50% of the operated patients. Hypoparathyroidism could be a result of careless or inadequate preparation during the surgical procedure. There is a variety of proposed options for the prediction of the incidence of hypocalcaemia. The most effective of them are the peri-operative and intra-operative measurements of the parathyroid hormone (PTH) level. METHODS: A prospective study was performed on 100 patients who underwent total thyroidectomy from January 2007 to June 2008. The total calcium level and intact human PTH (iPTH) levels were measured 24 hours before as well as 1 hour and 24 hours after the surgery. THE AIM: The goal of the study was to assess the potential correlation between the iPTH levels after the operation and the development of hypocalcaemia. The possible prediction value of postoperative iPTH levels was to be assessed. RESULTS: We have presented a significant correlation between early iPTH measurement and the risk of hypocalcaemia. Moreover, a significant correlation between the iPTH level one hour after operation with the calcium level 24 hours after the operation was demonstrated. CONCLUSION: Early postoperative assessment of iPTH levels can be used to identify the group of patients at risk of hypocalcaemia after thyroidectomy. Pre-emptive calcium supplementation can lead to the avoidance of complications causing prolonged hospital stay and most importantly to prevent severe hypocalcaemia. PMID- 20306909 TI - Open incisional hernia repair under local anaesthesia. AB - BACKGROUND: The Authors give an accurate description of a method of incisional hernia repair with an open technique, under local anaesthesia. The aim of this work was to show the feasibility and safety of an open preperitoneal mesh technique, as well as giving a description of technical details and the results of incisional hernia repair under local anaesthesia. METHODS: Between January 1994 and February 2008, 129 patients underwent an open mesh surgical procedure for incisional hernia. Using some simple selection criteria: maximal diameter of the hernia orifice not greater than 10 cm, the reducibility of the hernia sack, the absence of bowel obstructive symptoms, 71 patients (55.03%) were selected to be submitted to a local anaesthesia procedure, performing an open mesh repair. RESULTS: The median operative time was 101 min. The intra-operative measurement of the hernia defect showed that: in 24 patients (33.8%) it was < 3 cm, in 37 patients (52.2%) up to 10 cm and in ten patients (14%) > 10 cm. There were only two conversions to general anaesthesia (2.8%). Among the other 69 patients only four patients (5.7%) showed transient intra-operative bradycardia. All the other 69 patients (97.2%) had immediate postoperative deambulation. Forty-four of them (63.4%) were discharged within 24 h. During follow-up (12-168 months) only two recurrences (2.8%) were registered. CONCLUSIONS: This experience clearly shows that local anaesthesia for incisional hernia repair with a open preperitoneal mesh technique is feasible, safe, and effective, having a low intra-operative risk, being cost-effective and showing very good long-term results. PMID- 20306910 TI - Diagnosis and treatment of mesenteric tumours. AB - PURPOSE: To reveal clinical and diagnostic findings in patients with mesenteric tumours and to give an insight into the follow-up of these patients. BACKGROUND: Primary tumours of the mesentery are very infrequent. These tumours are cystic or solid and show benign or malignant clinical behaviour. In this article, we report clinical and radiological findings from eight cases of mesenteric tumours. PATIENTS AND METHODS: This study included eight patients with mesenteric tumours who underwent computed tomography in the Department of General Surgery, Baskent University, between December 2003 and April 2007. RESULTS: Three mesenteric tumours were solid and five had cystic patterns. Seven were excised totally on laparotomy and one was excised on laparoscopy. None of the patients showed malignant progression. CT showed mesenteric cysts in only two cases, but failed to show solid tumours: the pre-operative diagnosis was made accurately in just (2/8) 25% of the patients. CONCLUSIONS: It can be concluded that pre-operative CT is generally helpful, but inconclusive in an accurate diagnosis of mesenteric tumours. Surgery is required to make a definitive diagnosis of mesenteric tumours and to avoid complications. PMID- 20306911 TI - Right colonic diverticulitis: an uncommon disease in western countries. AB - BACKGROUND AND AIMS: Right colonic diverticulitis is not a frequent disease and its management is still controversial. In this study we describe our experience. MATERIAL AND METHODS: We retrospectively reviewed all patients operated on because of a right colonic diverticulitis in our surgical unit. All patients were treated laparoscopically. Demographics, diagnostic and surgical results were recorded. RESULTS: Between January 1994 and January 2007, 11 patients (7 males and 4 females) mean age 53 +/- 9 years (range 39-68), ASA 1: 6 patients, ASA 2: 4 patients, ASA 3: one patient, and BMI 27.8 (range 25-31), had right colonic diverticulitis. Four patients underwent emergency operations: one for peritonitis and three with an erroneous diagnosis of acute appendicitis; seven were operated on electively. There were no deaths or complications. The mean postoperative hospital stay was 5.6 days (range, 3-9). After a mean follow-up of 6.3 years (range 1-13) all patients of this series are symptom-free. INTERPRETATION AND CONCLUSION: Right colon diverticulitis diagnosis remains difficult. A pre operative imaging screening is necessary to successfully face this challenging disease. Laparoscopy is a safe and effective method to treat these patients. Colectomy should be considered a good therapeutic option for right colonic diverticulitis, although a conservative approach could be proposed in selected cases. PMID- 20306912 TI - Volar and dorsal mid-shaft forearm plating using DCP and LC-DCP: interference with the interosseous membrane and forearm-kinematics. AB - PURPOSE: To clarify if dorsal plate osteosynthesis of the forearm shaft is associated with impingement of the interosseous membrane (IOM) and if rotational kinematics of the forearm are influenced. BACKGROUND: Forearm fractures are treated by separate incisions. Osteosynthesis via one approach in proximal forearm fractures was associated with higher rates of synostosis. It has been claimed that this is due to IOM impingement. MATERIALS AND METHODS: 16 forearms of fresh frozen cadavers were dissected until only radius, ulna and the IOM remained. To preserve physiological forearm rotation, the elbow joint, the distal radio-ulnar joint and the carpus remained intact. In group 1, LC-DC and DC plates were placed on the flexor aspect of the respective bone. In group 2, the plates were placed ulnodorsal and radiodorsal. The distance between the plates and their effect on the IOM were investigated in a newly designed forearm simulator and measured in 30 degrees, 60 degrees and 90 degrees of pronation and supination respectively. RESULTS: The IOM was affected in neither group. There was no interference of the kinematics in group 1. In group 2, plate contact appeared in one pair in both types of plate. The plates were significantly closer in all positions in group 2. There was no difference between the various plates in the two groups. CONCLUSION: Dorsal plate osteosynthesis of the forearm shaft is not associated with an impingement of the IOM. Malpositioning of the plates is more likely to be of more effect in dorsal plate positioning and leads to interference with the kinematics. PMID- 20306913 TI - Oral fluvastatin reduces the severity of peritoneal adhesions in rats. AB - BACKGROUND: The aim of the study was to investigate the effect of fluvastatin on peritoneal adhesion formation. METHODS: 48 female Wistar-albino rats weighing 200 220 g were divided into four groups each containing 12 rats. Group I was sham, Group II was the control group, while Group III was given 10 mg/kg/day (28 days) oral fluvastatin. In Group IV, 10 mg/kg fluvastatin was administered intraperitoneally at the time of laparotomy but the rats died from that dose. After laparotomy on day 14, caecal serosal abrasions and punctuate haemorrhagies were performed. On day 28, laparotomies were repeated. Adhesions were graded and tissue samples were taken from incisions and adhesions. Hydroxyproline contents representing adhesions were measured quantitatively. On the 28th day, blood samples were taken to measure the tissue-type plasminogen activator (t-PA) activity. RESULTS: There were significant differences between the groups for adhesion severity (p < 0.0001), hydroxyproline content and t-PA activity of the adhesions (p < 0.0001). Analysis of the grading of adhesions documented significant differences between all groups. When the hydroxyproline content and t PA activity of the adhesions was analyzed, there were significant differences between groups II, I and III, but the difference between group I and group III was not statistically significant. CONCLUSIONS: The data presented in this study demonstrate that the oral administration of the HMG-CoA reductase inhibitor fluvastatin reduced intra-abdominal adhesion formation. PMID- 20306914 TI - A comparison of three fibrinolytic agents in prevention of intra-abdominal adhesions. AB - PURPOSE: Three different drugs affecting the coagulation process at various stages were studied for their effectiveness in preventing intra-peritoneal adhesion formation in rats. MATERIAL AND METHODS: Forty female Wistar-Albino rats divided into four groups based on the drugs administered during the experimental laparotomy and caecal abrasion: the control group--no drug administered, the intra-peritoneal tissue plasminogen activator (TPA) group, the subcutaneous fondaparinux sodium (FS) group and the intra-peritoneal activated drotrecogin alfa (ADA) group. After two weeks, intra-peritoneal adhesions were macroscopically and microscopically scored. RESULTS: The macroscopic scores of the three groups were similar but all lower than the control group (p = 0.002). Inflammation (p = 0.023) and fibrosis (p = 0.019) scores were lower in just the ADA group when compared to the control group. CONCLUSIONS: All three agents were effective in preventing adhesions when compared to the control group. Nevertheless, ADA seemed the most effective except when considering clinical applicability, in which case FS seemed to offer the greatest advantage. PMID- 20306915 TI - Acute and chronic gastric volvulus: radical different prognosis and management. Case report. AB - Gastric volvulus is an uncommon entity. Management is principally surgical. Diagnosis is often delayed because of the non-specific nature of the symptoms. The authors report two cases of gastric volvulus seen in a six month period. The first is an acute presentation diagnosed by computed tomography with incarceration and necrosis of the stomach, the transverse colon and great omentum. The issue was immediate laparotomy for total gastrectomy, colectomy, terminal colostomy and omentectomy. The patient survived, and the colostomy was closed and continuity restored three months later. The second one is a chronic form diagnosed by gastroscopy and barium swallow radiography. The treatment was elective with closure of the hiatus, Nissen procedure and gastropexy. The pathophysiology, classification and treatment of those two kinds of volvulus are briefly reviewed. PMID- 20306916 TI - A dermoid cyst of the round ligament clinically misdiagnosed as incarcerated inguinal hernia. AB - We present a case of a dermoid cyst located in the round ligament in a patient with a preliminary diagnosis of inguinal hernia. The dermoid cyst was diagnosed based on MRI findings and confirmed histopathologically. Dermoid cyst (mature teratoma) is a congenital cystic tumour formed by the well-developed (mature) tissues of at least two of the three germinal layers. It is mainly encountered in the gonads. Location within the round ligament is quite rare. Due to the anatomical localization of the round ligament, dermoid cysts within it or other inguinal canal masses are usually misdiagnosed as inguinal hernia. However, when an inguinal canal mass is encountered, despite the higher hernia frequency, a proper suspicion and investigation with regard to masses in this area could be extremely important in preventing intraoperative surprises. PMID- 20306917 TI - Pseudo-tumoral hepatic tuberculosis: a report of two cases. AB - Tuberculosis involving the liver in the absence of active pulmonary or miliary tuberculosis is very rare. The inflammatory pseudo-tumoral form is an entity difficult to diagnose. We report two patients, who underwent laparoscopic segmentectomy for suspected malignant tumour. Pathology showed tuberculoid granuloma with central caseous necrosis in both patients. The diagnosis in the first patient was made retrospectively on the resection specimen, whereas an active pre-operative work-up for tuberculosis diagnosis (biopsy and Polymerase Chain Reaction) remained futile in the second patient. The management of pseudo tumoral hepatic tuberculosis needs a multidisciplinary concertation and a surgical approach is often the best way to ensure the diagnosis. PMID- 20306918 TI - Inflammatory myofibroblastic tumour (IMT) of the liver: a report of two cases. AB - Inflammatory myofibroblastic tumour (IMT) is an uncommon mass lesion composed of myofibroblasts and mixed inflammatory infiltrate that rarely undergoes malignant transformation. Although IMT was originally reported in the lung, it is now recognised that it can occur in a variety of organs. Hepatic localisation of IMT is less frequent. Here we report two cases of IMT in the liver. They underwent hepatic resections with the diagnosis of FNH and Klatskin tumour. The pathological diagnosis of the tumour was IMT. We conclude that in the management of IMT in the liver, surgical excision is the primary choice, in order to obtain a definitive diagnosis as well as to relieve symptoms, and strict follow-up after surgery is required for the timely detection of recurrence. PMID- 20306919 TI - Non-Meckel's ileal diverticulitis with perforation: a rare cause of acute right lower quadrant pain. AB - A man, aged 74, presented with a rare clinical entity of an acute surgical abdomen similar to acute appendicitis. This case showed a non-Meckel's ileal diverticulitis that was complicated with a diverticular perforation and associated peritonitis. This is a very rare but potential life-threatening surgical emergency, mimicking the clinical presentation of acute appendicitis. The subject of small bowel non-Meckel's diverticulitis is reviewed because of the rarity of this condition and the diagnostic challenges it poses. PMID- 20306920 TI - Multiple intestinal intussusceptions in Peutz-Jeghers' syndrome: a case report. AB - Peutz-Jeghers' syndrome (PJS) is an autosomal dominant inherited disease, which is characterized by mucocutaneus pigmentation and hamartomatous gastro-intestinal polyps. Intussusceptions can easily occur in patients with PJS. Repeated laparotomy with resections and eventual short bowel syndrome is a major problem in these patients. We present a 20-year-old woman with multiple intestinal intussusceptions. Multiple enterotomies and intestinal resections were performed to achieve a longer symptom-free period. PMID- 20306921 TI - Quintuple primitive malignant neoplasms. A case report. AB - The authors describe the case of a patient who developed during 31 months, five malignant tumours, three synchronous and two metachronous. The primitive origin and the long interval of time between the occurrence of each tumour, allow to set them in the group of Multiple Primitive Malignant Neoplasm. The authors, reviewing the classifications and the pathogenesis of these tumours, underline the importance of the follow-up in oncology patients and emphasize the role of nosographic setting in order to plan the most suitable therapeutic approach. PMID- 20306922 TI - Familial multiple lipomatosis: a case report. AB - Lipoma is the most common type of soft tissue tumour. Multiple lipomas localised in different areas of the body are rare and can occur in specific hereditary syndromes. Familial multiple lipomatosis is a rare benign hereditary syndrome with a proposed autosomal-dominant inheritance. We present the case of a 67-year old man with this disease. Clinical features, genetic evidence, and treatment options are reviewed. PMID- 20306923 TI - Rupture of the common iliac artery following anal sex. AB - We describe the case of a young man admitted with acute onset of pain and defense in the left iliac fossa a few hours after rectal introduction of a dildo. At laparotomy a retroperitoneal haematoma was found along with a dissection of the left common iliac artery. No rectal perforation was identified. Aorto-iliac prosthetic bypass was necessary for repair. PMID- 20306924 TI - Gastroduodenal artery pseudoaneurysm ruptured in the common bile duct. AB - A pseudoaneurysm of the gastroduodenal artery (GDA) is the rarest splanchnic artery aneurysm, comprising fewer than 10% of these lesions. Bleeding into the gastrointestinal tract is the most rapidly fatal complication of an arterial visceral pseudoaneurysm, affecting 4-10% of patients. We present an unusual case of a GDA pseudoaneurysm that ruptured in the common bile duct, and that was successfully treated by partial resection and hepatic artery reconstruction. The postoperative evolution was favourable and the CT performed six months later disclosed the absence of a vascular tumour. PMID- 20306925 TI - Contribution to FDG-PET/CT diagnostics and post-operative monitoring of patients with mycotic aneurysm of the thoracic aorta. AB - Bacterial infection of the aorta is a life threatening condition calling for timely diagnostics and therapy. In the short communication presented here, the authors offer a case report on a patient of 70 years of age with aneurysm of the descending aorta caused by salmonella. The advantages of a new diagnostic hybrid modality are demonstrated and also the possibility of using it in the course of long-term monitoring of patients. PMID- 20306926 TI - Resection of blind ending bifid ureter in a patient with grade V vesicoureteric reflux. AB - Blind-ending bifid ureter is an extremely rare congenital anomaly. The authors report on a 13-year-old boy who presented with a previous diagnosis of right duplicated ureter and who had undergone a bilateral ureteroneocystostomy for vesicoureteral reflux in another clinic. The revision showed right blind-ending bifid ureter. The embryology, clinic and treatment of this anomaly is discussed. PMID- 20306927 TI - Techniques for supra-aortic trunk preservation in thoracic endovascular aneurysm repair. AB - Stent graft placement for aneurysmal disease of the aortic arch and proximal descending aorta is limited by the need to preserve flow to the supra-aortic trunks. Whilst extra-anatomical bypass and procedures combining open and endovascular arch repair are currently used in this setting, less invasive totally endovascular solutions have been described. These include in-situ fenestration of a thoracic stent graft using a retrograde approach from the target vessel to the lumen of the main device, to which it is connected by a smaller covered stent. Alternatively, so-called 'chimney' stents have been used, placing a parallel stent alongside the main device, connecting the aortic branch vessel with the native aortic lumen proximal to the seal zone of the main thoracic device. We review these techniques and discuss the merits and potential disadvantages of each procedure. PMID- 20306928 TI - Donor face reconstruction in a case of facial allotransplantation: technical note. AB - Families of organ donors are much more reluctant to approve donation of the corneas, face, and hands than of internal organs. The idea to "sacrifice" the face of a dead loved one is shocking to many. Moreover, most national laws, including Belgian laws, demand respect for the corpse. When mourners view an open coffin, visible parts such as the hands and face should appear normal. Hence, careful donor face reconstruction is required in a case of facial allotransplantation. We present a technique for donor face reconstruction that is both expedient and cost-effective. Instead of laboratory-cured silicone or acrylic polymers with internal and external coloration, an A-silicone impression material with a 2-minute set time and external colouring is used. PMID- 20306929 TI - History of cardiac surgery in Belgium. Part III: Evolution from 1960 to the present day. PMID- 20306930 TI - Concerns: management of common bile duct stone late after laparoscopic Roux-en-Y gastric bypass for obesity. Acta Chir Belg 2009; 109: 820-823. PMID- 20306931 TI - Spiritual disciplines, modern brain research and Bosch's psychological model of human dysfunction. AB - First I discuss aims and methods of spiritual disciplines from all times and ages. Difficulties that people experience in maintaining spiritual disciplines are described. Modern brain research sheds light on the question as to why this is so. The new psychotherapy of the Dutch psychologist Bosch is presented, which takes into account new insights of modern brain research and which bears striking similarities with universal spiritual disciplines. Some similarities are presented and implications of the findings are discussed. PMID- 20306932 TI - Exploring the meaning and role of spirituality for women survivors of intimate partner abuse. AB - Literature on trauma, coping and spirituality has introduced new questions about protective factors in the healing process for intimate partner abuse survivors (IPA). This qualitative study explores the relationship between spirituality and IPA with three focus groups of twenty-two women IPA survivors residing in a shelter. A content analysis revealed central themes that explicate the meaning and role spirituality plays for participants. Viewed as a salient dimension, spirituality provides strength, influences outcomes and assists in the regulation of behavioral responses in a positive manner in terms of participants' traumatic IPA victimization. Practice implications are discussed. PMID- 20306933 TI - Does pastoral counseling work? A pilot study of delinquent boys. AB - This is a study of the relationship between pastoral counseling interventions and recidivism in a small sample of 16 delinquent adolescent males in residential treatment programs where such interventions were routinely available. One or more of three pastoral counseling protocols were utilized with the youths who were assessed as demonstrating one or more of the spiritual needs addressed by the protocols and who were open to the intervention. Analysis showed a significant Spearman correlation (r = .588; p = .008) between pastoral counseling and low recidivism (measured as re-arrests since discharge at the time of the follow-up contact) suggesting that the pastoral counseling may be a contributing factor to successful treatment. PMID- 20306934 TI - Insecure attachment in couples' relationships. AB - Couples who are emotionally estranged even though they live together cannot really commit to each other. Their relationship is usually interwoven with painful, mostly unconscious and unaddressed attachment issues. These couples are characterized by a constant fear of intimacy, the leaving/approaching dynamics which provoke further fear in one of the partners and is therefore unstopable. With the help of therapeutic interventions, we will search for the roots of their avoidant behavior and try to creatre a save, intimate place which we call a sacred place, where the healing process can begin. PMID- 20306935 TI - Liminality in death care: the grief -work of pastors. AB - Proximity with issues of death and dying is one of the troubling aspects of ministry for many clergy. This article articulates the role of the minister as a liminal figure, a person who serves a ritual function in times of grief and loss, and who enables the creation of meaning in the in-between space between death and life. This liminal role is compared with that of the funeral director, as elaborated by Thomas Lynch in his memoir, The Undertaking. This paper suggests that while the liminal position is a difficult one for the pastor, it also provides some of the deepest satisfactions of ministry. PMID- 20306936 TI - The practice of interpersonal forgiveness in the personal and professional lives of clergy. AB - This study examined the effects of a forgiveness education intervention on the psychological wellbeing of clergy and their ability to apply interpersonal forgiveness skills in their personal lives and in professional conflict situations depicted in hypothetical interpersonal conflict vignettes. A sample of 32 clergy from eleven different denominations was randomly assigned to either an experimental or control group. Significant results were found between the groups in regards to the participants' willingness to forgive and the use of forgiveness strategies for resolving the interpersonal conflict situations. PMID- 20306937 TI - Hospital chaplains' involvement in a randomized controlled multidisciplinary trial: implications for spiritual care and research. AB - Chaplains' involvement in spirituality and health research can contribute something vital and unique to these investigations. It can also provide opportunity for professional growth and increased effectiveness. This article describes the authors' experience as co-investigators in a randomized controlled trial involving patients with a life expectancy of less than five years receiving radiation therapy for advanced cancer. It also discusses the application to clinical settings and other research. PMID- 20306938 TI - Pastoral formation process for seminarians a new model for developing psychologically healthy pastors. AB - The Pastoral Formation Program is based on systems theory. It examines the connections between family of origin history and a healthy career in ministry. Through exploration of a seminarian's spiritual, emotional, and psychological health, participants gain insight into personal family history and how it can lead to repetition. Program goals are to develop clergy with a clear understanding of their history, its impact on their professional life, and skills that will help them in ministry. PMID- 20306939 TI - Educating CPE supervisors: a grounded theory study. AB - This qualitative study was designed to cull the wisdom of CPE supervisors doing especially competent supervisory education and to develop a theory of CPE supervisory education. Grounded theory methodology included interviewing 11 supervisors and coding the data to identify themes. Four primary dimensions emerged along with a reciprocal core dimension, Supervisory Wisdom, which refers to work the supervisors do in terms of their continuing growth and development. PMID- 20306940 TI - The therapeutic covenant: a psychotheological pathway to dynamic engagement. AB - Covenant language resides at the heart of all great spiritual journeys. The covenant is rigid and flexible, secure and dangerous, constant and ever changing. On the surface a covenant can be understood as an agreement between the client and the therapist. Beneath the surface lies the dynamic nature of the covenant, a nature based on the emotional quality a client brings, couple with the therapist capacity to support emotional integrity in the process of covenant development. In its simplicity the covenant becomes the guiding force that leads the client and therapist into the complex world of the unconscious. This article seeks to access the theological and psychological ramifications of integrating covenant theory into the psychotherapeutic process. Herein we encounter a dynamic that animates change in the client while at the same time making significant demands upon the therapist. PMID- 20306941 TI - Jesus and people with disabilities: old stories, new approaches. AB - According to some authors, the healing narratives in the New Testament have fuelled destructive attitudes toward disability among Christians. The purpose of this paper is to explore a subset of Jesus' miracle healings for more constructive messages, and for guidance about pastoral care for people with disabilities. Of twenty-nine miracle accounts found in the four gospels, five were selected for this study that deal with physical disability in individual persons. Using the socio-rhetorical interpretive method, the stories are mined for themes regarding spiritual aspects of healing, identity, faith, sin and touch. PMID- 20306942 TI - Defining and overcoming barriers between Euro-American chaplains and African American families. AB - This article describes various communication barriers between Euro-American chaplains and African American families which prevent effective spiritual care. These barriers include covert and deeply internalized racism, belief in false ideologies, persistent stereotyping, and being unaware of white privilege. Proposes potential solutions of acknowledging ones own race; becoming sensitive to the history and continuing oppression of Euro-Americans toward African Americans; building multicultural competence through education; and building equal-status relationships with African American individuals. PMID- 20306943 TI - The metaphor of experience and the experience of metaphor: critical reflection on a contemplative process toward aliveness and compassion. AB - An epistemological web invites critical reflection and the possibility of new ideas emerging in the space between experience and different ways of thinking. A web offers a postmodern method of a hermeneutic of experience and a way of knowing that creates space for a robust, flexible, dynamic process of critical reflection and discovery. The following article utilizes an inter-textual epistemological web (see Figure 1, p. 4) to answer the question, "Do metaphors of experience and experiences of metaphor during contemplative healing prayer with a spiritual director nurture a transformational process toward aliveness and compassion?" How can one discover and communicate this reality in dialog with Hebrew scripture, psychoanalytic theory, affective neuroscience and ways of thinking about contemplative transformation? PMID- 20306944 TI - The dresser. PMID- 20306945 TI - The Twenty-Third Psalm revisited. PMID- 20306946 TI - Reflections on grief. PMID- 20306947 TI - Trial run. PMID- 20306948 TI - Finding God admidst the Greensburg tornadoscape: resurrection and restoration. PMID- 20306949 TI - Trees and education. PMID- 20306950 TI - "If I die tomorrow, chaplain, you know everything...". PMID- 20306951 TI - Tones and tunes as a spiritual practice. PMID- 20306952 TI - Parable of six students in a supervised pastoral education unit. PMID- 20306953 TI - Turn around. PMID- 20306954 TI - On turning 80. PMID- 20306955 TI - "Colonel". PMID- 20306956 TI - One century of Kirschner wires and Kirschner wire insertion techniques: a historical review. AB - A century ago, in 1909, Martin Kirschner (1879-1942) introduced a smooth pin, presently known as the Kirschner wire (K-wire). The K-wire was initially used for skeletal traction and is now currently used for many different goals. The development of the K-wire and its insertion devices were mainly influenced by the change in operative goals and by the introduction of antibiotics. The first versions of the Kirschner wire were hammered through a predrilled hole into the bone, but later on drilling became the standard technique of insertion. Drilling is considered a simple way of implanting, with many advantages, such as percutaneous and atraumatic insertion. However, this technique also has its disadvantages like temperature elevation, resulting in osteonecrosis and heat related complications. Despite these complications the K-wire is now standard for the treatment of hand fractures, worldwide. PMID- 20306957 TI - Paediatric hip fractures: a systematic review of incidence, treatment options and complications. AB - Hip fractures in children are rare; when not properly treated, they can be disastrous for the growing child. We present the incidence, causes, treatment options and possible complications. A good understanding of classification and treatment options is of great importance to minimize complications. A clear evidence-based algorithm, however, cannot be proposed. Further multi-centre studies should be performed to come to such a consensus on the treatment of pediatric hip fractures. PMID- 20306958 TI - Management of full thickness rotator cuff tears. A survey amongst members of the Flemish Elbow and Shoulder Surgeons Society (FLESSS). AB - The purpose of this study was to determine the attitude of the members of the Flemish Elbow and Shoulder Surgeons Society (FLESSS) towards full-thickness tears of the rotator cuff and their treatment in their daily practice. A survey form was sent to 123 shoulder surgeons between January and March 2008. Seventy-three responses were returned, a 60% response rate. For 40% of the respondents, arthro CT was the gold standard diagnostic method for assessment, 36% preferred arthro MRI. Arthroscopic, mini-open and open cuff repair were preferred by 64%, 19% and 16% of the responders respectively. Fewer years in practice, a higher volume of shoulder operations and a higher volume of rotator cuff repairs were significantly correlated with a higher percentage of arthroscopic repairs (p > or = 0.001). With respect to the type of fixation, 91% preferred screw-type anchors, and of these 81% were metal anchors. Our results show that all-arthroscopic techniques are becoming the gold standard for the repair of full-thickness tears of the rotator cuff in Flanders. PMID- 20306959 TI - Treatment of chronic wounds at the olecranon. AB - Surgical resection of the olecranon bursa may be complicated by wound healing problems. Treatment with debridement and primary skin closure can be attempted. We reviewed eight patients in whom this approach had failed. In four patients we achieved wound healing with a pedicled flap (three antecubital fasciocutaneous island flaps and one radial forearm flap). In three patients the wound healed after closure of the skin and immobilization of the elbow in extension. In one elderly patient with diabetes and rheumatoid arthritis an antecubital fasciocutaneous island flap failed. It can be concluded that the antecubital fasciocutaneous island flap and primary closure of the skin followed by immobilization of the elbow in extension can be used to treat chronic wounds at the olecranon. PMID- 20306960 TI - Mechanism of loosening of the Souter-Strathclyde total elbow replacement evidence from revision surgery. AB - Nine Souter-Strathclyde humeral and ulnar components retrieved from revision surgery for aseptic loosening were examined macro- and microscopically. The wear patterns were compared and photographed. Humeral components demonstrated no evidence of wear. All ulnar components exhibited similar wear patterns. Six of the nine exhibited macroscopic evidence taking the form of deep linear grooves on either the medial or lateral articulating surfaces. Microscopic examinations revealed wear on all nine, exhibited as disruption of the polyethylene machining lines on the articular surfaces, but almost complete preservation on the central gliding ridge. We believe our observations are explained by 'rocking' of the humeral component on the ulnar as a result of the congruent surfaces of the Souter-Strathclyde prosthesis, which resist rotational and translational movements, characteristic of the normal elbow. PMID- 20306961 TI - Is there a need for reconstruction after excision of the distal ulna for giant cell tumour? AB - Giant cell tumour rarely involves the distal ulna; the literature has sporadic cases reported, and the need for reconstruction after distal ulnar resection remains controversial. The uncommon presentation often leads to diagnostic delays, and some of the cases reported have attained large sizes prior to diagnosis, leading' to procedures which range from soft tissue stabilization to bone graft reconstruction of the surgical defect. We analyzed our cases with specific reference to the need for additional reconstruction; the radiological and functional outcome of extraperiosteal distal ulna resection without reconstruction in 4 patients with giant cell tumour of the distal ulna was assessed at a mean follow-up of 9 years post surgical excision. In our experience there was no radiological evidence of recurrence, radioulnar convergence and ulnar translocation of the carpus. Functional outcome was graded as excellent in 3 and good in one patient. In conclusion, it could be suggested that there is no need for reconstruction after distal ulna resection for GCT as an adequate functional outcome is seen even in late diagnosed cases. Reconstructive procedures, which come at the cost of additional morbidity and complications, and requires special technical skills, are not routinely justified for this rare condition. PMID- 20306962 TI - Negative ulnar variance has prognostic value in progression of Kienbock's disease. AB - The radiographic files of 70 patients with Kienbock's disease were analyzed. Ulnar variance, carpal height and Kienbick stage were determined. A significant difference in ulnar variance was seen between early and late stages of the disease. In later stages there is a marked negative ulnar variance, not caused by bone apposition on the radius. We hypothesize that negative ulnar variance encourages further progression of the collapse of the lunate, while neutral or positive ulnar variance seems to protect the lunate against deformation. PMID- 20306963 TI - Retroversion of the contralateral adult acetabulum after previous Perthes' disease. AB - Retroversion of the adult acetabulum following a previous Legg-Calve-Perthes disease (LCPD) is found in 30-40% of the patients. It is known that in LCPD there may also be morphologic changes in the nonaffected controlateral acetabulum. We investigated the prevalence of retroversion of the contralateral acetabulum in a group of adult patients with a history of LCPD. We found this morphology in 11 out of 36 patients (31%). The aetiology and its relation to Perthes' disease are discussed. PMID- 20306964 TI - Reliability and reproducibility of classification systems for Legg-Calve-Perthes disease: a systematic review of the literature. AB - Several classification systems are in use for Legg-Calve-Perthes disease. Three of them: Catterall, Salter Thompson and Herring (Lateral Pillar) are most commonly used. There has been debate on which is most reliable. The purpose of this paper was to systematically analyse the literature when the classifications were compared. The Ovid (Medline) Database was used and the MeSH terms Perthes Classification and Reliability were inserted. Eleven studies were retrieved but only five were suitable for analysis as they attempted to compare the classifications. Most studies used kappa agreements as the principal outcome measure, although intraclass coefficients and percentage agreements were also used. Only four studies assessed for both intraobserver reproducibility and interobserver reliability. A further study from the references appendages was found to be suitable, and was included in the analysis. Kappa ranged from poor to fair (Salter Thompson), fair to moderate (Catterall) and moderate to good (Herring). The outcome from Legg-Calve-Perthes disease is extremely variable. Inconsistent interpretation of the plain films may explain this, although it is likely this is multifactorial. The papers in this study show that on balance, the Lateral Pillar classification was most reliable, probably secondary to ease of use. A persistent theme was that the subchondral fracture line in the Salter Thompson system was difficult to interpret and not always present. It also showed that whilst reliability and reproducibility tended to improve with experience, disagreement was not always restricted to more junior personnel. Each classification has its merits but reliability and reproducibility remains unsatisfactory. Digital technology in the future may help delineate the lesions better and improve agreement. PMID- 20306965 TI - Clinical and radiological results of the stemmed Mc Minn cup in hip revision surgery. AB - Results with the stemmed McMinn acetabular cup in revision total hip arthroplasty with acetabular defects have been scarcely reported. We report our experience and radiological outcome with the stemmed cup in three Dutch orthopaedic departments. Twenty four patients with a median age of 69 years were operated between 1999 and 2005. Immediate postoperative radiographs were evaluated and compared with those at follow-up. The center of rotation was restored in 75% of the hips. Adequate alignment was seen in 71%. The mechanical failure rate was 38%. The cup was removed because of sepsis in three patients. Two patients had a dislocation (1 chronic). After 5 years, definite radiological loosening of the prosthesis was noted in 4 patients. PMID- 20306966 TI - Ilizarov treatment for aseptic delayed union or non-union after reamed intramedullary nailing of the femur. AB - The authors reviewed eight patients treated with an Ilizarov frame for a non infected delayed union or non-union after reamed intramedullary nailing of the femoral diaphysis. The hardware was completely removed in all cases but two, in which the distal fragment of a broken nail was left in situ. In five cases without shortening, progressive compression was applied. In the other three patients a simultaneous lengthening was performed using an additional percutaneous osteotomy. All patients achieved a good consolidation, with an average time to healing of 32 weeks and restoration of length and alignment if necessary. Bone grafting was never required, illustrating the sufficient biological potential for repair in non-infected femoral non-union. PMID- 20306967 TI - Femoral component rotation and Laurin angle after total knee arthroplasty. AB - One of the main problems after total knee arthroplasty is pain in the patellofemoral joint, which in some cases leads to revision surgery. Rotation of the femoral component has a significant influence on the path followed by the patella within the patellofemoral joint. We examined the influence of rotation of the femoral component after total knee arthroplasty on patellar tilt. We retrospectively analysed the radiographs of 48 patients who underwent primary LCS total knee arthroplasty without patella resurfacing and without lateral release. Rotation of the femoral component was determined using Kanekasu's technique and patellar tilt assessment according to Laurin on Merchant's views. This radiographic study confirmed a highly significant correlation between external rotation of the femoral component and a decrease in patellar tilt following TKA. Furthermore, we found a highly significant correlation between pre- and postoperative patellar tilt angle. PMID- 20306968 TI - A comparison of post-op haemoglobin levels and allogeneic blood transfusion rates following total knee arthroplasty without drainage or with reinfusion drains. AB - The effects of re-infusion drains on the rate of allogeneic blood transfusion and post-op haemoglobin levels in Total Knee Arthroplasty were examined. A group of 22 patients undergoing primary Total Knee Arthroplasty using a CBCII Constavac Stryker re-infusion drainage system were compared with a group of 30 patients, matched for age, sex and type of prosthesis but without any drain usage. The re infusion drain.group had a significantly lower day 1 and day 3 post-operative haemoglobin compared to the non-drainage group. The re-infusion drain group had a higher allogenic transfusion rate compared to the non-drainage group. There were no significant differences between the two groups regarding the rate of wound and transfusion related complications and mean length of post-operative stay. We found that reinfusion drains were ineffective in reducing allogeneic transfusion requirements as compared with non-drainage in total knee arthroplasty. PMID- 20306969 TI - Arthroscopy of the knee in elderly patients: cartilage lesions and their influence on short term outcome. A retrospective follow-up of 183 patients. AB - We reviewed all patients of 65 years and older (n=183), who underwent a knee arthroscopy between 2004 and 2005. The purpose of our study was to determine the frequency and severity of cartilage lesions and their influence on short-term clinical outcome. Signs of osteoarthritis (OA) were absent or minor on pre operative plain radiographs in 30.5% of patients, but only 5.3% of patients were found during arthroscopy to have no obvious cartilage lesions. WOMAC and KOOS scores did not clearly correlate with severity of cartilage damage, but some WOMAC and KOOS subscales scored significantly lower when cartilage lesions were located on the lateral side. Forty-one patients eventually underwent TKA after a mean period of 14 months. In conclusion, cartilage lesions were visualized in almost every case even when pre-operative radiographs suggested differently. The higher the Kellgren-Lawrence grade of cartilage lesions on preoperative radiographs, the higher the risk for a TKA in the short term. Forty-seven percent of patients with Kellgren-Lawrence grade 4 lesions needed a TKA during the time period of the study. PMID- 20306970 TI - Incidence and aetiology of talipes equino-varus with recent population changes. AB - This study looks at the changing incidence and aetiology of congenital talipes equinovarus due to the recent population changes within the area. Between 1st June 1992 and the 31st May 2006, 83 consecutive children (121 feet) born with fixed talipes equinovarus (TEV) were assessed and treated (an incidence of 1.6 per 1000 live births) in an observational longitudinal cohort study assessing associated factors. There were 17 syndromal cases in the fixed group (20.8%), 6 cases of non-syndromal distal arthrogryposis (7.2%), and a strong family history in 12 cases (14.5%). This study would suggest that genetic and primary causes of fixed TEV are more common than previously considered. Many of the primary aetiologies were diagnosed months or years after birth. PMID- 20306971 TI - Acute stress disorder and post-traumatic stress disorder following traumatic amputation. AB - Traumatic amputations are important causes of acute stress disorder and post traumatic stress disorder. In this study, we aimed to find out the occurrence rate of symptoms of acute and post-traumatic stress disorder after traumatic amputations and according to this, to assess the psychiatric status of the patients in the postoperative period. Twenty-two patients with traumatic limb amputation who were treated in our institution were retrospectively evaluated. During the early post-traumatic period, the patients were observed to determine whether they needed any psychiatric supportive treatment. During the follow-up period, after the sixth month from the trauma, the patients were referred to the psychiatry department and they were evaluated to determine whether they needed any psychiatric supportive treatment, by clinical psychiatric examination and use of the 'post-traumatic stress disorder scale' (Clinician Administered Post traumatic Scale, or CAPS). Twenty-one (95.5%) of 22 patients were male, one (4.5%) female. Mean age of the patients was 40.8 years (range: 15 to 69). During the early posttraumatic period, 8 (36.3%) of these patients consulted the psychiatry clinic following the orthopaedists' observations. Five (22.7%) of these patients needed psychiatric supportive treatment for acute stress disorder. After the 6th month (6 months to 5 years), 17 (77.2%) had chronic and delayed post-traumatic stress disorder and needed psychiatric supportive treatment. Patients who have sustained a traumatic amputation may need psychiatric supportive treatment in the late period after the trauma. As we orthopaedic surgeons treat these patients surgically, we should be aware of their psychiatric status. PMID- 20306972 TI - Anterior-only instrumentation and grafting after L5 corpectomy for non-traumatic lesions. AB - Anterior decompression and reconstruction have been used for the treatment of various conditions at the lumbosacral junction, particularly those necessitating corpectomy because of destruction due to primary or secondary bone tumour or infection. The authors conducted a prospective study on 15 consecutive patients who underwent L5 (L4-L5 in 3 cases) corpectomy for tumour or infection, between 2000 and 2005: 6 for tumour, 7 for tuberculous spondylitis, and 2 for pyogenic spondylitis. Corpectomy, bonegrafting (tricortical iliac bone graft or titanium mesh-bone graft) and anterior-only instrumentation (screw-plate or screw-rod) were performed via a retroperitoneal approach. One month of bed rest yielded additional stability. The patients were followed up for an average of 39.7 months (range: 7-73 months). Pain relief and neurological recovery were excellent. Solid fusion was obtained in all patients. There were no cases of plate or screw failure. Three patients with metastases died after 7, 17, and 13 months, in spite of successful fusion. No recurrence was noted in all 9 patients with spinal infection. The results observed indicate that grafting and anterior-only instrumentation and grafting is an effective and safe procedure for reconstruction of the lumbosacral junction following L5 (or even L4-L5) corpectomy; it may obviate the need for additional posterior stabilization in selected patients. PMID- 20306973 TI - Non-tuberculous thoracic and lumbar spondylodiscitis: single-stage anterior debridement and reconstruction, combined with posterior instrumentation and grafting. AB - Debridement is warranted for the treatment of nontuberculous spondylodiscitis in case of neurological compromise, deformity, instability, abscess formation, extensive destruction, intractable pain or failure of medical management. The additional use of instrumentation is still controversial, but might fight infection and yield stability. The purpose of this retrospective study was to evaluate the outcome of 16 cases of non-tuberculous thoracic or lumbar spondylodiscitis treated with anterior debridement and reconstruction (tricortical graft or titanium mesh cage), combined with single-stage posterior instrumentation and grafting. The pathogens identified were: Brucella (5), coagulase-negative Staphylococcus aureus (4), Staphylococcus aureus (3), unidentified (4). All 16 infections resolved without recurrence. Bony union was obtained in all cases. Fourteen out of 16 patients (87.5%) were completely relieved of pain and fully active, an excellent result according to Macnab's criteria; the other two patients obtained a good result. All 7 patients who had a neurological deficit improved. There were two superficial infections, which healed with debridement and antibiotics. A single iliac vein injury was primarily repaired. In conclusion, the proposed technique is an effective and safe treatment for pyogenic spondylodiscitis, if surgery is mandatory. PMID- 20306974 TI - Application guidelines for dynamic knee joint analysis with a dual fluoroscopic imaging system. AB - The widespread availability of mobile digital fluoroscopic systems with dynamic imaging capabilities places this type of motion analysis within reach of many research groups. With the addition of the second fluoroscope though, and the incorporation of a treadmill to analyze gait, the fluoroscopic analysis technique, which was once a rather straightforward method, has become more complex. Therefore, the purpose of the present manuscript was to provide a comprehensive review of the various processes that are associated with the dynamic knee joint motion analysis, including patient selection, construction of three-dimensional knee models, fluoroscopic scanning, and matching. PMID- 20306975 TI - Premature epiphyseal fusions in beta thalassaemia. AB - Thalassemia patients are now living longer due to better transfusion methods and diagnostic awareness. To see whether this longevity is associated with orthopaedic disability, especially physeal growth defects, we examined 105 patients aged between 5-25 years for evidence of clinically detectable premature epiphyseal fusions (PEF). Ours is a center focussed on transfusion dependent beta thalassemia (TDBT) patient management, and so detailed transfusion records related to age at first transfusion, regularity of transfusions and pre transfusional haemoglobin (Hb) levels were available. Five (4.7%) patients had deformities or limb length discrepancies, which lead to the detection of PEF. All patients with PEF had pre transfusion haemoglobin levels of less than 8 gm/dL. On comparing with the literature, we found that the prevalence of clinically detectable PEF in TDBT patients has decreased with better blood transfusion regimes. Though the pathogenesis of PEF is yet to be conclusively established, it is apparent that better control of the disease to maintain pre-transfusional haemoglobin levels consistently above 8 gm/dL in the first decade, can decrease the occurrence of PEF. PMID- 20306976 TI - A modified Weaver-Dunn procedure without need for internal fixation. AB - The shoulder as the most mobile joint in the body has a complex anatomy providing it with an increased range of motion, at the expense of its stability. The complex of ligaments and tendons around the acromioclavicular joint (ACJ) is prone to injury especially during sporting activity or following falls onto the apex of the shoulder. The original classification of ACJ dislocations having been modified by Rockwood suggests that types III to VI injuries may benefit from surgical intervention. Many procedures have been described to correct the deformity in the ACJ and to reestablish its ligamentous support. We describe a modification to the Weaver-Dunn procedure, which aims to establish a stable reduction with bone-to-bone healing, provided by bone plug fixation with Ethibond suture. PMID- 20306977 TI - Ilizarov treatment for extreme bilateral genu recurvatum in a pseudoachondroplasia patient: a case report. AB - The history of a 17-year-old female patient with pseudoachondroplasia, with an extreme bilateral genu recurvatum due to tibial growth disturbance, is presented. She was treated by the Ilizarov method over a nine- month period for consecutive bilateral correction of the lower legs, leading to an excellent functional result. The authors advocate the Ilizarov method as the treatment of choice for severe juxtaarticular osseous deformities, where the technical limits of a standard osteotomy with internal fixation are being exceeded. PMID- 20306978 TI - Living history in current orthopaedic hip surgery: intrapelvic teflon granuloma after total hip replacement. AB - The teflon hip arthroplasty design was used by Sir John Charnley in the early 60's but was taken off the market due to high complication rates. A case is reported of an intrapelvic granuloma after total hip arthroplasty following the use of a teflon socket. This appears to be the last surviving patient treated by Sir John Charnley using a Teflon hip socket design. PMID- 20306979 TI - Patient positioning for microdiscectomy nearly fatal because of iatrogenic obstruction to inferior cardiac inflow caused by hepatic hernia. AB - A routine microdiscectomy was complicated by an inferior cardiac inflow obstruction caused by compression of the inferior vena cava. This was due to further upward migration of an existing hepatic hernia through a right-sided diaphragmatic defect. Understanding the pathogenesis of this problem allowed the surgical team to adjust the positioning of the patient. After installing the patient on a different frame, the prone position was well tolerated and the microdiscectomy could be performed without the need to repair the diaphragmatic hernia. PMID- 20306980 TI - Post-traumatic calcific myonecrosis of flexor hallucis longus. A case report and literature review. AB - Calcific myonecrosis is a rare, late complication of compartment syndrome in the lower extremity. In this condition an entire single muscle of the leg is replaced by a fusiform mass with central liquefaction and peripheral calcification. Calcific myonecrosis presents a diagnostic dilemma to the clinician; it has to be considered in the differential diagnosis of a calcifying soft tissue tumour in the lower extremity. The purpose of this report is to highlight the importance of recognition of the lesion and its key clinico-pathological presenting features leading to appropriate management. We describe the unique presentation, diagnosis and surgical management of calcific myonecrosis involving only the flexor hallucis longus muscle of the leg in a middle-age adult. We found MRI Scan as the most useful method of investigation. Diagnosis can be confirmed by yellow-brown paste like material within the lesion intra-operatively or by aspiration and further by histology. We recommend complete excision of the lesion and closure of the wound with compression dressing, to avoid secondary infection. PMID- 20306981 TI - Cryptococcal lymphadenitis diagnosed by fine needle aspiration cytology: a review of 15 cases. AB - OBJECTIVE: To review the cases of cryptococcal infection presenting primarily with lymphadenopathy and diagnosed on fine needle aspiration cytology (FNAC) and to evaluate the various cellular reactions in this infection. STUDY DESIGN: Retrospective review of 15 cases of cryptococcal lymphadenitis diagnosed on FNAC between 1999 and 2007. RESULTS: A total of 15 cases of cryptococcal lymphadenitis were diagnosed, out of which 10 occurred in a setting of immunosuppression, and in 5 cases there was no obvious immunocompromised clinical setting. Eight patients had human immunodeficiency virus infection, and 2 were post-renal transplant. These patients presented with lymphadenopathy at various sites, with size ranging from 0.5 to 3 cm. The aspirate in most of the cases was fluid material. Detailed cytologic examination of the smears revealed a predominantly chronic inflammatory infiltrate and showed the presence of numerous organisms of varying size present both intracellularly as well as extracellularly. The 2 patients with renal transplant had a low load of organisms. Three cases showed well-formed granulomas, and a giant cell reaction was seen in 9 cases. The periodic acid-Schiff/Alcian blue stain was applied in all cases and confirmed the mucopolysaccharide capsule. One case represented dual infection with Mycobacterium tuberculosis and Cryptococcus. Unlike other fungal infections, the granulomatous reaction and associated inflammatory response in cryptococcal infection is very slight or absent. CONCLUSION: FNAC can expedite an accurate diagnosis of cryptococcal lymphadenitis, which helps in the prompt initiation of treatment. The cellular response and the organism load are variable. PMID- 20306982 TI - Correlation of positron emission tomography with fine needle aspiration biopsies in head and neck malignancy. AB - OBJECTIVE: To investigate whether a correlation between fine needle aspiration cytology and positron emission tomography (PET) exists in the preoperative screening, staging and diagnosis of head and neck cancer. STUDY DESIGN: We retrospectively correlated fine needle aspiration biopsy (FNAB) and PET scan in patients with head and neck lesions. RESULTS: There were 92 FNABs with corresponding PET scan in 83 patients. Mean standard uptake value (SUV) for benign lymph nodes was 5.05 (SD, 5.79), and 13.56 (SD, 6.38) and 16.99 (SD, 19.04) for squamous carcinoma and other malignancies, respectively. Ideal SUV cutoff value was determined to be 6.0. Of 66 malignant FNABs, 52 had an SUV > or = 6, 8 had an SUV < 6, and 6 were interpreted as "hypermetabolic." Of 26 benign FNAB (SUV was available for 17), 8 were interpreted as "hypermetabolic" and 1 as "not hypermetabolic." Of those with SUVs reported, 15 were < 6 while 2 were > or = 6. CONCLUSION: Lesions with SUV 6 are more likely to harbor malignancy, while lesions with repeatedly negative FNAB in the context of SUV > 6 should be considered for open biopsy. Further, lesions with SUV < 6 may harbor malignancy and therefore fine needle aspiration biopsy is also recommended. PMID- 20306983 TI - Bone marrow aspiration findings in kala-azar. AB - OBJECTIVE: To describe the bone marrow aspiration cytologic findings in visceral leishmaniasis. STUDY DESIGN: Bone marrow aspiration of 204 documented cases of kala-azar were reviewed in order to find aspiration clues other than typical intrahistiocytic and free Leishman-Donovan bodies. Aspiration findings were divided into different groups of common, uncommon as well as atypical/unusual findings. RESULTS: Common findings were granulomas, intrahistiocytic and free typical organisms, plasma cells with or without inclusions, eosinophilia, free floating cytoplasmic bodies with or without Leishman bodies, granular bodies and erythroid hyperplasia. Uncommon findings were: intracellular (non-histiocytic) organisms, hemophagocytosis, plasma cells with abnormal crystalline inclusions, leukemic blasts and necrosis. Atypical/unusual findings were: spore-like organisms, regular or irregular shape of aggregates of organisms (flower-like, ball-like, rosette-like, doughnut-like and platelet-like), intracytoplasmic granule-like organisms (kinetoplast only), pseudo-Pelger Huet, increased vessels, fibroblasts, Reed-Sternberg-like cells, multinucleated giant cells, tart cells and foamy cells. CONCLUSION: Knowledge of common, uncommon and unusual/atypical bone marrow aspiration findings of kala-azar may help arrive at a correct diagnosis; avoid unnecessary workups, such as sophisticated molecular techniques; and avoid fatal outcomes in untreated or non-diagnosed cases. PMID- 20306984 TI - Expression of estrogen receptor alpha and estrogen receptor beta in fine needle aspirates of breast carcinoma. AB - OBJECTIVE: To evaluate the expression of estrogen receptor beta (ERbeta) in fine needle aspirates (FNAs) and correlate the findings with its expression in tissue sections. STUDY DESIGN: In 38 cases of breast carcinoma, expression of estrogen receptor alpha (ERalpha) and ERbeta in aspirates and tissue sections was correlated with the cytologic and histologic grade of the tumor. RESULTS: ERalpha and ERbeta were expressed as nuclear staining in 80% and 90% of the cases in tissue sections and 47% and 45% of the cases in aspirates, respectively. Tissue expression of ERalpha (grade 1, 81%; grade 2, 100%) and ERbeta (grade 1, 94%; grade 2, 100%) was greater than in grade 3 tumors (ERalpha, 50%; ERbeta, 70%). In FNAs they were equally distributed in the different cytologic grades. In aspirates 30% of ERalpha negative tumors were positive for ERbeta, while in tissues 75% of ERalpha-negative tumors were positive for ERbeta (p = 0.007). CONCLUSION: Demonstration of ERbeta on FNA smears is feasible. It helps identify the specific subcohort of ERbeta-positive tumors in ERalpha-negative breast cancers; that may have therapeutic importance. PMID- 20306985 TI - Detecting p53 immunoexpression in esophageal mucosa with exfoliative cytology in individuals at risk for squamous cell carcinoma of the esophagus. AB - OBJECTIVE: To determine the prevalence of p53 expression in cytologic smear collected by the RS Balloon in high-risk individuals, and test its yield in the cytologic screening of squamous cell carcinoma of the esophagus (SCCE). STUDY DESIGN: Asymptomatic individuals at risk for SCCE underwent esophageal exfoliative cytology with the RS Balloon immediately followed by upper gastrointestinal endoscopy with biopsies of unstained areas after iodine mucosal staining of the esophagus. For each patient, cytologic expression of p53 was compared with the worst endoscopic biopsy diagnosis and the histologic expression of p53. RESULTS: One hundred seventy-one individuals were submitted to the study's protocol. There were 8 lost cases (4.7%) due to inadequate cytologic samples. The final sample consisted of 163 individuals where 150 were male (92%), mean age of 52.6 +/- 12.0 years old. There were 3 cases of dysplasia/SCCE. Immunohistochemical expression of p53 protein was positive in 38 patients (23.6%), with basal layer expression in 29 (76.3%), middle layer expression in 8 (21.1%) and superficial layer in 1 (2.6%). All patients with dysplasia/SCCE had positive immunohistochemical expression of p53 protein. Immunocytochemical expression of p53 protein in cytologic smear was negative in all cytology samples. CONCLUSION: The negative results of immunocytochemical expression of p53 protein suggest that its use does not contribute to improving the performance of conventional cytology of the esophagus in the screening for SCCE and its precursor lesions. PMID- 20306986 TI - Apoptosis and cell proliferation correlated with tumor grade in patients with ampullary carcinoma. AB - OBJECTIVE: To evaluate apoptosis and cell proliferation on cytologic specimens (smears) from endoscopic retrograde cholangiopancreatography in patients with ampulary carcinoma and to correlate that relationship with the grade of the tumors. STUDY DESIGN: Forty patients (23 males and 17 females) aged 45-81 who underwent endoscopic retrograde cholangiopancreatography were diagnosed by cytology as having ampullary adenocarcinoma and the diagnoses were confirmed histologically after an operation. All smears were stained using Papanicolaou and Giemsa stain. Apoptosis was assessed using terminal digoxigenin-labeled dUTP nick end labeling (TUNEL assay) and cell proliferation using MIB-1 monoclonal antibody by the alkaline phosphatase method. RESULTS: The TUNEL indices were 0.4 +/- 0.07, 0.91 +/- 0.33 and 3.1 +/- 0.9 in well, moderate and poorly differentiated ampullary carcinoma, respectively. The differences in both TUNEL and MIB-1 labeling indices were statistically significant between well, moderately and poorly differentiated ampullary carcinoma, and a positive correlation was found between TUNEL and the MIB-1 indices. CONCLUSION: Apoptosis (cell death) and cell proliferation increase as the grade of the differentiation decreases in ampullary carcinoma, suggesting a rapid turnover of the tumor cells with lower grates of differentiation, and apoptosis may play an important role in the growth of the tumors in patients with ampullary carcinomas. PMID- 20306987 TI - Trends in inflammatory status of the vaginal flora as established in the Dutch national screening program for cervical cancer over the last decade. AB - OBJECTIVE: To describe recent trends in the prevalence of cytologic patterns of the vaginal flora (koilocytosis, Trichomonas, dys-bacteriosis, Candida, Gardnerella, Actinomyces, Chlamydia trachomatis) over the last decade. STUDY DESIGN: From 1996 to 2005 > 500,000 cervical smears were screened in the context of the Dutch national screening program on a 5-year basis. Data from the first screening period were compared with those of the second screening period. RESULTS: Prevalences differed from 34.8 for dysbacteriosis to 0.2 for C trachomatis. Bacterial imbalance (dysbacteriosis, unequivocal Gardnerella and Trichomonas) showed a decline in all age groups. Cases of human papillomavirus (HPV)-related koilocytosis have dramatically increased among young women (30 and 35 years). CONCLUSION: Bacterial imbalance of the vaginal flora has significantly decreased during the past decade in all age cohorts. Campaigns on consciousness of vaginal hygiene might have contributed to this amazing effect. We ought to be concerned about the increase in HPV-related koilocytosis. PMID- 20306988 TI - Gynecologic infections seen in cervical smears in Kuwait. AB - OBJECTIVE: To study the different gynecologic infections seen in cervical smears in Kuwait. STUDY DESIGN: Over a 6-year period (2002-2007), a total of 42,294 cervical smears were studied in Mubarak Al-Kabeer Hospital, Kuwait. Conventional and ThinPrep (Cytyc Corp. Boxborough, Massachusetts) smears were first screened by cytotechnicians and finally reported by cytopathologists, Smears showing inflammation were analyzed with reference to Kuwaiti women. RESULTS: Of the 41,748 (98.7%) patients with satisfactory smears, inflammatory changes were observed in 17, 593 (42.1%). Specific infection was identified in 2,679 (15.2%) cases, of which 60.8% were Kuwaitis. The infections seen were Candida sp (73.8%), Trichomonsa vaginalis (11.9%), human papillomavirus (HPV99) (8.2%), Actinomyces like organisms (3.4%), Chlamydia trachomatis (2.2%) and herpes simplex virus (0.5%). No significant difference was found in the proportion of infectious agents among Kuwaiti and non-Kuwaiti women except marginally higher T vaginalis (10.9% vs 13.4%, p = 0.05) among non-Kuwaitis. Candida sp was the most detectable infectious agent in both Kuwaiti (74.6%) and non-Kuwaiti women (72.4%). Chi2 for trend revealed an increasing proportion of smears from Kuwaiti women found with specific infections (p = 0.049) as compared to those of non-Kuwaitis over the years. CONCLUSION: The prevalence of infections identified on cervical smears was found to be almost similar in Kuwaiti and non-Kuwaiti women except for T vaginalis, which was higher among non-Kuwaitis as compared to Kuwaitis (10.9% vs. 13.4%, p = 0.051). The Candida sp was the most detectable infectious agent, 74.6% in Kuwaiti and 72.4% in non-Kuwaiti women, followed by T vaginalis, the second and HPV being the third. PMID- 20306989 TI - Role of fine needle aspiration cytology, cell block preparation and CD63, P63 and CD56 immunostaining in classifying the specific tumor type of the lung. AB - OBJECTIVE: To determine whether CD63, p63 and CD56 are useful in the diagnostic evaluation of cytologic samples of pulmonary malignancy. STUDY DESIGN: We explored the utility of using a panel of 3 antibodies, CD63, p63 and CD56, for the diagnosis of lung cancer in cytologic samples consisting of 40 cases of cell block sections and previously Papanicolaou-stained cytologic smear slides. RESULTS: The positive rates for CD63, p63 and CD56 were as follows: adenocarcinoma (18/19), (0/19), (0/19), for small cell lung carcinoma (3/8), (0/8), (8/8), and for squamous cell carcinoma (0/13), (12/13), (0/13). All p63 positive cases were squamous cell carcinoma, and all CD56 positive cases were small cell lung carcinoma. CD63 was positive in the majority of adenocarcinomas. CONCLUSION: The panel of CD63, p63 and CD56 appears to be useful in the diagnostic evaluation of cytologic samples of pulmonary malignancy. PMID- 20306990 TI - Fine needle aspiration diagnosis of necrotizing eosinophilic abscess clinically mimicking hepatic neoplasia: a case report. AB - BACKGROUND: Eosinophilic hepatic pseudotumors (EHP) are known complications of visceral larva migrans (VLM). By radiologic studies, EHP can be suspicious for primary or metastatic hepatic neoplasia. Diagnosis of an EHP by fine needle aspiration (FNA) led to the diagnosis of Toxocara VLM in a patient with suspected hepatic neoplasia. CASE REPORT: A 38-year-old Cambodian man had hepatitis B and chronic hepatitis with grade III portal fibrosis diagnosed in 2003. He had had negative routine alpha-fetoprotein and radiologic screening for hepatic neoplasia until 2006 when abdominal computed tomography revealed a 1.6 x 1.2-cm, ill defined hypodense lesion in segment VII. Biopsy was recommended in order to exclude hepatocellular carcinoma. FNA of the lesion contained abundant Charcot Leyden crystals, degenerating eosinophils and necrotic debris. Work-up for nematode larva migrans was recommended. Toxocara antigen IgG titer was significantly elevated leading to a presumptive diagnosis of VLM, and therapy for Toxocara-induced VLM was given. CONCLUSION: Identification of abundant Charcot Leyden crystals and necrotic eosinophils in an FNA of the liver led to appropriate ancillary diagnostic tests and therapy for visceral larva migrans. PMID- 20306991 TI - Aspiration cytology of mesenchymal hamartoma of the chest wall in an infant: a case report. AB - BACKGROUND: Mesenchymal hamartoma of the chest wall is an extremely uncommon lesion of infants. Radiologic features simulate a malignant neoplasm; however, pathologic examination demonstrates an admixture of fibroblasts, benign cartilage and woven bone. There is a paucity of cytologic reports of this rare entity in the available literature. CASE: A 5-month-old infant presented with a large right chest wall swelling. Radiologic investigation demonstrated lytic destruction of the right 7th, 8th and 9th ribs with a large soft tissue mass. Fine needle aspiration smears showed lobules of hyaline cartilage and a few spindle cells with abundant chondromyxoid matrix. A cytologic diagnosis of a benign chondroid, possibly hamartomatous lesion was given, which was confirmed as mesenchymal hamartoma on histopathologic examination. CONCLUSION: Mesenchymal hamartoma is a rare chest wall lesion that can be diagnosed on cytology, provided that the cytopathologist is aware of this uncommon entity and appreciates the benign cytologic features. PMID- 20306992 TI - Pyothorax-associated lymphoma diagnosed by preoperative pleural effusion aspiration cytology: a case report. AB - BACKGROUND: Pyothorax-associated lymphoma (PAL) is a comparatively rare tumor, and it is difficult to definitively diagnose it preoperatively, especially in patients with only pleural thickening without mass formation. Pleural effusion aspiration cytology is a useful and easy diagnostic method for a large number of chest diseases. However, the cytologic findings of PAL have been rarely described. Here we report on the cytologic findings in a patient with PAL, manifested by pleural thickening without mass formation, and which was diagnosed preoperatively by pleural effusion aspiration cytology. CASE: A 64-year-old man was admitted to our hospital because of pleural thickening involving an empyema sac located in the left thorax and rapidly increasing pleural effusion. He had a 30-year history of chronic empyema and a 10-year history of diabetes mellitus. Left pleural effusion aspiration cytology showed malignant lymphoma. The patient was admitted to our hospital for PAL treatment. Because of poor respiratory function, he only underwent decortication with complete resection of the thickening pleural peel. However, he was well, without recurrence, 5 years after the operation. The histologic examination revealed that lymphoma cells were located only in the thickening pleural peel. CONCLUSION: This is a very rare case of PAL diagnosed by preoperative aspiration cytology for an increasing pleural effusion. This report demonstrates that pleural effusion aspiration cytology can be valuable for the diagnosis of PAL. PMID- 20306993 TI - Fine needle aspiration cytology diagnosis of primary renal lymphoma involving the pleura: a case report. AB - BACKGROUND: Primary renal lymphoma is a rare disease (< 1% of kidney lesions). We present a case of renal large B-cell type non-Hodgkin's lymphoma (NHL) with right sided pleural involvement. CASE: A 70-year-old man was admitted with persistent, painless, macroscopic hematuria for 1 month. Ultrasound examination, abdominal computed tomography and magnetic resonance imaging techniques revealed a large tumor in the right kidney extending in the perirenal area. The patient underwent a radical nephrectomy for suggested renal cell carcinoma. He developed thoracic pain and pleural effusion in the 10 days after surgery. The pleural fluid was cytologically processed using conventional and ThinPrep (Cytyc Corporation, Boxborough, Massachusetts, U.S.A.) cytopreparatory techniques, slides were Papanicolaou and Giemsa stained, and immunocytochemistry was performed on the ThinPrep slides. The cytologic examination of the fluid specimen revealed a highly cellular smear composed of dispersed neoplastic cells of intermediate and large size. Immunocytochemically, the neoplastic cells were: CD45 (LCA) (+), CD20 (+), CK7 (-), CK20 (-), NSE (-), CD45 RO (UCHL-1) (-) and CD30 (-). On cytomorphologic and immunocytologic examination, the specimen fulfilled the criteria of a large B-cell type NHL. Histologic evaluation of the nephrectomy specimen revealed an infiltrating, diffuse large cell renal NHL, B-cell type, of immunoblastic and centroblastic morphology. This NHL was considered a renal primary because no peripheral lymphadenopathy or hepatosplenomegaly was revealed by the imaging techniques. CONCLUSION: Cytomorphologic and immunocytologic examination revealed the typical features of a renal large B-cell type NHL in a case with pleural involvement. PMID- 20306994 TI - ALK+ anaplastic large cell lymphoma with cohesive, perivascular arrangements on cytology, mimicking a soft tissue sarcoma: a report of 2 cases. AB - BACKGROUND: An accurate recognition of a lymphoma at an extranodal site is essential to avoid unnecessary excisions. Fine needle aspiration cytology (FNAC) has been recognized as a useful tool in the primary diagnosis of soft tissue tumors. An anaplastic large cell lymphoma (ALCL), occurring in soft tissues, poses a diagnostic challenge. We present the cytomorphology of 2 cases of anaplastic lymphoma kinase (ALK)+ ALCL that displayed a perivascular arrangement, thereby mimicking a sarcoma. CASES: The patients were aged 16 and 9 years. While the former presented with multiple nodular soft tissue and bony lesions over the body, the latter complained of an axillary lump. FNAC smears in both cases showed pleomorphic cells, arranged in loosely cohesive groups around blood vessels and scattered singly, with prominent nucleoli and abundant, finely vacuolated cytoplasm. Interspersed were a few cells with embryoid nuclei. Differential diagnoses included a rhabdomyosarcoma and a lymphoma. On biopsy and immunohistochemistry, tumor cells were positive for vimentin, LCA, EMA, CD30 and ALK. CONCLUSION: ALCL should be considered in the differential diagnosis of pediatric soft tissue tumors, especially in cases with multifocal involvement. The presence of cohesive, perivascular arrangements on FNAC should not detract a cytologist for keeping this possibility in mind. Further, a careful search for the typical "hallmark" cells should be made. PMID- 20306995 TI - Primary cardiac B-cell lymphoma presented as heart tamponade and atrioventricular block: a case report. AB - BACKGROUND: Primay cardiac lymphoma is rare, and its diagnosis is not determined until autopsy. CASE: A 49-year-old man presented with heart tamponade and atrioventricular block. Bloody pericardiac effusion showed a monotonous proliferation of atypical large mononuclear cells, which demonstrated a lambda light-chain monoclonality by the fluorescence-activated cell-sorter method and clonal rearrangement bands by Southern blot analysis of the IgH gene. Transvenous biopsy excised from the right atrial tumor was diagnosed as diffuse large B-cell lymphoma. He underwent chemotherapy and permanent pacemaker implantation and is alive and well. CONCLUSION: Liquid cytology of cardiac effusion was very useful for rapid diagnosis, leading to a better prognosis. PMID- 20306996 TI - Ectomesenchymal chondromyxoid tumor of the tongue masquerading as pleomorphic adenoma on fine needle aspiration cytology smears: a case report. AB - BACKGROUND: Ectomesenchymal chondromyxoid tumor (ECMT) of the tongue is a relatively uncommonly recognized entity, first characterized in 1995 when Smith et al described the clinicopathologic features in 19 cases. The reported incidence of this tumor is still limited, and the recognition of its presenting features is not widespread. Although the tumor histology is typical, the fine needle aspiration cytology (FNAC) features can be mistaken for those of other myxoid lesions. CASE: A 47-year-old woman presented with a nodule on the dorsal surface of the tongue that had been present for 3 months. Fine needle aspiration smears from the nodule showed abundant myxoid to fibrillary stromal fragments and clusters of oval and polygonal to spindled cells with uniform nuclei. A cytologic diagnosis of pleomorphic adenoma was given. Subsequent histopathologic evaluation of the excised tumor revealed ECMT. CONCLUSION: Because of its abundant chondromyxoid stroma, ECMT shares morphologic similarities with other myxoid lesions, especially the salivary gland tumors, on histologic evaluation. The FNAC features of this tumor have not been reported before. The lack of awareness of ECMT as a tumor entity and nonexposure to the cytologic features may cause errors in the cytologic diagnosis. PMID- 20306997 TI - Cytologic findings of low grade endometrial stromal sarcoma with sex cord-like differentiation: a case report. AB - BACKGROUND: To report the cytologic characteristics of low grade endometrial stromal sarcoma with sex cord-like differentiation. CASE: A 49-year-old woman presented with hypermenorrhea, menorrhalgia and anemia. With a diagnosis of degenerated leiomyoma of the uterus, simple total hysterectomy was conducted. Histologic examination revealed cells with ovoid to short, spindle-shaped nuclei resembling endometrial stromal cells proliferating in a space-occupying manner and compressing and partially infiltrating the myometrium. Some tumor cells were arranged in sex cord-like form, and hyalinization was observed in the center of the cord. Low grade endometrial stromal sarcoma with sex cord-like differentiation was diagnosed. Touch imprint cytologic examination of the tumor showed cells containing scanty cytoplasm and ovoid to spindle-shaped nuclei with little atypia; they were scattered individually, aggregated in clusters, or arranged in cord or glandular form. Hyaline-like substance was present in abundance. The histologic characteristics of the endometrial stromal sarcoma with sex cord-like differentiation were confirmed by touch imprint cytology of the tumor. CONCLUSION: In this case of low grade endometrial stromal sarcoma with sex cord-like differentiation, cytologic examination revealed hyaline substance and tumor cells aligned in cord or glandular form. PMID- 20306998 TI - Fine needle aspiration cytology of benign fibrous histiocytoma of bone: a case report. AB - BACKGROUND; Benign fibrous histiocytoma (BFH) of bone is a very rare tumor, and almost all reported cases were diagnosed after surgical resection by histologic examination. We report a case in which cytologic features of BFH of bone were established preoperatively by fine needle aspiration (FNA). To the best of our knowledge, FNA findings of BFH of bone have not been previously reported. CASE: A 30-year-old man presented with pain in the right knee of 3 days' duration. Radiographs of the distal femur showed a lytic lesion. FNA biopsy followed by cytologic examination revealed highly cellular smears with spindle-shaped cells arranged in sheets, papillary fronds and storiform pattern. These cells had a moderate amount of cytoplasm and round to elongated nuclei with inconspicuous nucleoli. Multinucleate giant cells were occasionally seen. A cytologic diagnosis of Giant cell tumor of bone with a BFH component was rendered. Histology revealed a pure BFH of bone. CONCLUSION: The current case reveals the cytomorphologic features of BFH of bone. Cytology may permit the preoperative recognition of the lesion, allowing a more sound therapeutic approach. PMID- 20306999 TI - Fine needle aspiration appearance of parachordoma. PMID- 20307000 TI - Fine needle aspiration cytology of cysticercosis. PMID- 20307001 TI - Intraoperative cytology of subependymoma. PMID- 20307002 TI - Pancreatic pseudocyst disguised as chylous effusion. PMID- 20307003 TI - Epithelioid angiosarcoma. PMID- 20307004 TI - Rare diagnosis on aspiration cytology of parotid gland schwannoma. PMID- 20307005 TI - Comparison of liquid-based cytology and conventional filter preparations in urine: a possible serious pitfall. PMID- 20307006 TI - Fine needle aspiration cytology of malignant peripheral nerve sheath tumor of the tongue. PMID- 20307007 TI - Clear cell sarcoma of soft tissue: diagnostic dilemma in cytologic appearance. PMID- 20307008 TI - Pollen grains in sputum smear mimicking Toxocara eggs. PMID- 20307009 TI - Wavelet-synchronization methodology: a new approach for EEG-based diagnosis of ADHD. AB - A multi-paradigm methodology is presented for electroencephalogram (EEG) based diagnosis of Attention-Deficit/Hyperactivity Disorder (ADHD) through adroit integration of nonlinear science; wavelets, a signal processing technique; and neural networks, a pattern recognition technique. The selected nonlinear features are generalized synchronizations known as synchronization likelihoods (SL), both among all electrodes and among electrode pairs. The methodology consists of three parts: first detecting the more synchronized loci (group 1) and loci with more discriminative deficit connections (group 2). Using SLs among all electrodes, discriminative SLs in certain sub-bands are extracted. In part two, SLs are computed, not among all electrodes, but between loci of group 1 and loci of group 2 in all sub-bands and the band-limited EEG. This part leads to more accurate detection of deficit connections, and not just deficit areas, but more discriminative SLs in sub-bands with finer resolutions. In part three, a classification technique, radial basis function neural network, is used to distinguish ADHD from normal subjects. The methodology was applied to EEG data obtained from 47 ADHD and 7 control individuals with eyes closed. The Radial Basis Function (RBF) neural network classifier yielded a high accuracy of 95.6% for diagnosis of the ADHD in the feature space discovered in this research with a variance of 0.7%. PMID- 20307010 TI - PLEDs following control of seizures and at the end of life. AB - Periodic lateralized epileptiform discharges (PLEDs), an EEG pattern that is highly correlated with seizures, may represent an ictal pattern in some patients, but in other patients PLEDs persist despite the absence of seizures or after seizures have been controlled by anti-epileptic drugs. The tenacity of PLEDs was illustrated by continuous EEG recording in a 95-year-old woman with multiple old cerebral infarctions who had been admitted to the hospital because of seizures. The EEG showed PLEDs that were maximal in the left central region. These sometimes evolved into EEG seizure patterns, which were correlated with facial twitching. The seizures were controlled by anti-epileptic drugs (AEDs), but the PLEDs continued. The patient subsequently expired, with EEG monitoring still in progress. The PLEDs persisted as the patient developed agonal respirations. The interval between the epileptiform complexes gradually increased, and they stopped 40 seconds before disappearance of the other EEG background rhythms; cardiac arrest ensued less than 1 minute later. The resistance of the PLEDs to hypoxia reflects the robustness of the mechanisms that produced them, which may also account for their persistence in the face of AED treatment that stopped the seizures. PMID- 20307011 TI - Utilization of below-the-hairline EEG in detecting subclinical seizures. AB - Nonconvulsive status epilepticus (NCSE) is a serious condition commonly considered when evaluating a patient with altered mental status, and an electroencephalogram (EEG) is necessary for diagnosis. Neurology house staff often must make this diagnosis at times when no EEG technologist is available. We report our experience with abbreviated, emergency below-the-hairline EEGs (BTH EEG) performed by neurology residents at our institution over a 1-1/2 year period. We analyzed demographic and clinical data in relation to whether or not an ictal or periodic pattem was identified, and these results were compared to follow up EEGs. Thirty-nine studies were identified, ranging in duration from 3 min-13 hrs. Mean and median age of patients included was 53 (range 25-81 yrs); 21 were female. Seven of 39 BTH-EEGs showed at least one electrographic seizure, 9 more showed periodic discharges. Follow-up EEGs showed electrographic seizures in 6 of 39 patients, including 3 of the 7 with ictal BTH-EEG, and an additional 3 whose BTH-EEGs showed periodic lateralized discharges but no organized seizures. All 7 patients with ictal BTH-EEGs survived to discharge, vs. 23 of the remaining 32. We conclude that in selected cases, BTH-EEG is useful in detecting seizures and/or other epileptiform patterns. In our series, when NCSE was in question, the BTH-EEG showed these patterns 41% of the time. The BTH-EEG is a fast, non invasive, inexpensive tool that may save valuable time, especially when no other viable option is immediately available. This technique may be applicable more broadly, not just limited to centers with neurology residents. PMID- 20307012 TI - Amygdala lateralization at rest and during viewing of neutral faces in major depressive disorder using low-resolution brain electromagnetic tomography. AB - Neuroimaging experiments of amygdala activity during rest have shown abnormal amygdalar lateralization in Major Depressive Disorder (MDD). The current study is an exploratory investigation of the use of the neuroimaging technique Low Resolution Electromagnetic Tomography (LORETA) to measure current source density (CSD) in the amygdala. We examined seven adults with MDD and nine healthy control subjects at rest, and while they viewed images of emotionally neutral faces. The primary purpose was to compare the findings of LORETA with published findings using other neuroimaging techniques. Four frequency bands were examined: delta (1 3 Hz), theta (3-7 Hz), alpha (7-11 Hz), and beta (11-29 Hz). Results showed that for both MDD and control groups, the right amygdala displayed higher overall activity (across frequencies) than the left, both at rest, and while viewing neutral faces. Results also showed that controls displayed significant differences between resting and viewing neutral images across all four bands in the right amygdala, with all four bands having higher CSD values in the right amygdala. There were no significant differences in CSD values between rest vs. viewing neutral images in the MDD group. Findings suggest a more pronounced lateralization effect in normal healthy controls than in MDD subjects when changing from a resting (eyes-closed) condition to viewing faces without emotional valence. PMID- 20307013 TI - Event-related potentials elicited by the explicit and implicit processing of familiarity in faces. AB - Brain activity underlying explicit and implicit processing of face familiarity was assessed by Event-Related Potentials (ERPs) elicited by famous and unknown faces with happy or neutral expressions. A set of faces was presented in a familiarity judgment (explicit) task and another in an expression judgment (implicit familiarity) task. After recording, these tasks were repeated exchanging the stimuli, and post-recording behavioral data from the familiarity task were used for re-averaging EEG segments from the expression task. Both explicit and implicit processing of famous faces resulted in an enhanced N250. Explicit processing of famous faces was specifically associated with earlier N400 and P600, with increased activity within brain areas involved in identity processing around 250 and 450 ms. These findings suggest different brain dynamics for explicit and implicit face processing, and that implicit processing of the identity in the context of an expression task is mainly associated with the transient activation of face representations in memory. PMID- 20307014 TI - Post WISC-R and TOVA improvement with QEEG guided neurofeedback training in mentally retarded: a clinical case series of behavioral problems. AB - According to the DSM-IV, Mental Retardation is significantly sub-average general intellectual functioning accompanied by significant limitations in adaptive functioning in at least two of the following skill areas: communication, self care, home living, social/interpersonal skills, use of community resources, self direction, functional academic skills, work, leisure, health and safety. In pilot work, we have seen positive clinical effects of Neurofeedback (NF) applied to children with Trisomy 21 (Down Syndrome) and other forms of mental retardation. Given that many clinicians use NF in Attention Deficit Hyperactivity Disorder and Generalized Learning Disability cases, we studied the outcomes of a clinical case series using Quantitative EEG (QEEG) guided NF in the treatment of mental retardation. All 23 subjects received NF training. The QEEG data for most subjects had increased theta, alpha, and coherence abnormalities. A few showed increased delta over the cortex. Some of the subjects were very poor in reading and some had illegible handwriting, and most subjects had academic failures, impulsive behavior, and very poor attention, concentration, memory problems, and social skills. This case series shows the impact of QEEG-guided NF training on these clients' clinical outcomes. Fourteen out of 23 subjects formerly took medications without any improvement. Twenty-three subjects ranging from 7-16 years old attending private learning centers were previously diagnosed with mental retardation (severity of degree: from moderate to mild) at various university hospitals. Evaluation measures included QEEG analysis, WISC-R (Wechsler Intelligence Scale for Children-Revised) IQ test, TOVA (Test of Variables of Attention) test, and DPC-P (Developmental Behaviour Checklist) were filled out by the parents. NF trainings were performed by Lexicor Biolex software. NX-Link was the commercial software reference database used to target the treatment protocols, along with the clinical judgment of the first author. QEEG signals were sampled at 128 samples per second per channel and electrodes were placed according to the International 10-20 system. Between 80 and 160 NF training sessions were completed, depending on the case. None of the subjects received any special education during NF treatment. Two subjects with the etiology of epilepsy were taking medication, and the other 21 subjects were medication-free at the baseline. Twenty-two out of 23 patients who received NF training showed clinical improvement according to the DPC-P with QEEG reports. Nineteen out of 23 patients showed significant improvement on the WISC-R, and the TOVA. For the WISC-R test, 2 showed decline on total IQ due to the decline on some of the subtests, 2 showed no improvement on total IQ although improvement was seen on some of the subtests, however even these cases showed improvement on QEEG and DPC-P. This study provides the first evidence for positive effects of NF treatment in mental retardation. The results of this study encourage further research. PMID- 20307016 TI - Nonconvulsive status epilepticus presenting with throat clearing as part of clinical seizure semiology. AB - Oro-alimentary automatisms such as chewing movements, lip-smacking, repeated snuffling, swallowing and retching have been reported with seizures usually of temporal lobe origin. Throat clearing, usually along with other vegetative signs, has been reported in patients with temporal and rarely extra-temporal lobe epilepsy. We report a case of a 93-year-old woman admitted with acute right temporo-occipital stroke. Repeated throat clearing episodes raised suspicion for complex partial seizures. Video-EEG recording confirmed frequent right hemispheric focal seizures originating from the right posterior temporal area concordant with her cortical stroke. The value of throat clearing as a sign of complex partial seizures of temporal lobe origin and its lateralizing and localizing value is discussed. PMID- 20307015 TI - Magnetic resonance spectroscopy findings in photosensitive idiopathic generalized epilepsy. AB - Studies investigating the pathophysiology of epileptic photosensitivity indicate variable involvement of particular brain regions. Our aim was to identify metabolic differences between photosensitive idiopathic generalized epilepsy (IGE) patients and nonphotosensitive IGE patients and normal healthy subjects by using Magnetic Resonance Spectroscopy (MRS). Fourteen patients diagnosed with photosensitive IGE were investigated. The control groups consisted of 14 age- and sex-matched healthy volunteers and 14 IGE patients without photosensitivity. MRS measurements of N-acetylaspartate (NAA), choline-containing compounds (Cho), creatine (Cr) were performed in the frontal and occipital cortex and the thalamus bilaterally using a stimulated echo acquisition mode (STEAM) technique with a voxel size of 20 x 20 x 20 mm. The values of the patients with IGE were compared with those of the normal controls and within subgroups according to the clinical variables by appropriate statistical tests. Photosensitive IGE patients showed significantly decreased concentrations of NAA in the right frontal lobe and left thalamus, decreased NAA/Cr ratio in left thalamus and significantly increased concentrations of Cho/Cr ratio in the right frontal lobe and NAA/Cr in the left occipital lobe when compared to normal controls. Furthermore, left occipital NAA concentration increased and left thalamus NAA/Cr ratios were decreased from the IGE patients without photosensitivity but without reaching statistical significance. Our results support previous MR studies suggesting an asymmetrical neuronal dysfunction in favor of the dominant occipital cortex and thalamus in photosensitive IGE patients. PMID- 20307017 TI - Online removal of muscle artifact from electroencephalogram signals based on canonical correlation analysis. AB - The electroencephalogram (EEG) is often contaminated by electromyography (EMG). In this paper, a novel and robust technique is presented to eliminate EMG artifacts from EEG signals in real-time. First, the canonical correlation analysis (CCA) method is applied on the simulated EEG data contaminated by EMG and electrooculography (EOG) artifacts for separating EMG artifacts from EEG signals. The components responsible for EMG artifacts are distinguished from those responsible for brain activity based on the relative low autocorrelation. We demonstrate that the CCA method is more suitable to reconstruct the EMG-free EEG data than independent component analysis (ICA) methods. In addition, by applying CCA to analyze a number of EEG data contaminated by EMG artifacts, a correlation threshold is determined using an unbiased procedure. Hence, CCA can be used to remove EMG artifacts automatically. Finally, an example is given to verify that, after EMG artifacts were removed successfully from the EEG data contaminated by EMG and EOG simultaneously, not only the underlying brain activity signals but the EOG artifacts are preserved with little distortion. PMID- 20307018 TI - Work-induced changes in feelings of mastery. AB - Past theory and research indicate that conditions of work can have lasting effects on job incumbents. R. A. Karasek and T. Theorell (1990), for example, proposed that workers' feelings of mastery increase with levels of job demands and job control, and that these effects are mediated by the process of active learning. To test these propositions, 657 school teachers completed scales assessing job demands, control, active learning, and mastery on 2 occasions, 8 months apart. As hypothesized, job control predicted change in mastery, an effect that was mediated by active learning. Job demands had a weaker effect on change in mastery. The demands-mastery relationship was moderated by job control, so that under conditions of high control, but not low control, increasing job demands were associated with gains in mastery. The findings partially support R. A. Karasek and T. Theorell's (1990) predictions regarding the main, interactive, and mediated effects of job conditions on employee mastery. PMID- 20307019 TI - Predicting community opposition to inclusion in schools: the role of social dominance, contact, intergroup anxiety, and economic conservatism. AB - This study addresses community members' attitudes toward inclusion, the practice of including students with disabilities in regular education classroom settings. Participants in Study 1 were 271 community adults, completing measures of prior contact with people with disabilities, social dominance orientation (SDO), economic conservatism, intergroup anxiety, prejudice, and opposition to inclusion. Results from structural equation modeling indicated that amount of intergroup anxiety predicted opposition to inclusion via the mediator, prejudice toward people with disabilities, and that amount of prior contact indirectly predicted prejudice toward people with disabilities through intergroup anxiety. SDO positively predicted both intergroup anxiety and prejudice in the model, with prejudice also mediating between SDO and opposition to inclusion. Both SDO and economic conservatism failed to exhibit direct predictive relationships with opposition to inclusion. Participants in Study 2 were 161 community adults. Contact was shown to exert an indirect effect on prejudice via intergroup anxiety, whereas intergroup anxiety impacted inclusive attitudes via prejudice. SDO exerted both direct and indirect (via prejudice) effects on opposition to inclusion. PMID- 20307020 TI - Organizational strategy and employee outcomes: a person-organization fit perspective. AB - This study adopted a person-organization fit framework to examine (a) whether employees' perceptions of organizational strategy for adaptation predicted their commitment to their organization and their intentions to stay and (b) whether these 2 relationships were moderated by perceived job alternatives. Support was found for both hypotheses. Specifically, when there are numerous perceived job alternatives, employees who perceive a misfit between their company's strategy and their preferred strategy were less committed to their organization and less likely to stay than their fit counterparts. PMID- 20307021 TI - Psychometric properties of the Chinese version of the workaholism battery. AB - The authors designed the current study to examine the psychometric properties of the Chinese version of the workaholism battery (J. T. Spence & A. S. Robbins, 1992). Using the back-translation strategy recommended by R. Brislin (1980), the authors translated the original scale developed by Spence and Robbins. Factor analyses of responses from 1,235 full-time workers in Taiwan revealed a 5-factor solution. The reliability coefficients of the factors ranged from .58 to .88. Significant correlations between the 5 factors, the work-addiction risk test, career commitment, and job involvement provided evidence for convergent validity. Significant correlations between the 5 factors and criterion variables (emotional exhaustion, job satisfaction, and hours worked per week) provided evidence of concurrent criterion validity. Overall, the findings suggest that the Taiwanese workers conceptualize workaholism as 5 dimensions rather than the 2 or 3 dimensions that previous empirical studies (A. Kanai, M. Wakabayashi, & S. Fling, 1996; L. H. W. McMillan, E. C. Brady, M. P. Driscoll, & N. V. Marsh, 2002; J. T. Spence & A. S. Robbins, 1992) have suggested. The authors discussed implications and limitations of their findings. PMID- 20307023 TI - Siblings' motives for talking to each other. AB - The sibling relationship is an involuntary one that individuals often maintain throughout life (V. G. Cicirelli, 1995; M. A. Fitzpatrick & D. M. Badzinski, 1994; P. Noller & M. A. Fitzpatrick, 1993). The authors investigated interpersonal communication motives in sibling relationships to examine the way in which siblings voluntarily maintain their relationships with one another over time. R. B. Rubin, E. M. Perse, and C. A. Barbato (1988) identified 6 primary motives that people have for communicating: affection, control, escape, inclusion, pleasure, and relaxation. Participants were 323 individuals who reported on why they communicated with 1 of their siblings. The authors found differences between male and females participants and between intact and nonintact families. The number of siblings and the birth order of siblings also appeared to affect motives for communicating. The authors discuss the implications and limitations. PMID- 20307022 TI - Personal growth in the wake of stress: the case of mothers of preterm twins. AB - In a longitudinal study conducted in Israel, the authors compared mothers of preterm twins (n=64) with mothers of full-term single babies (n=75) and twins (n=72). The authors examined the contributions of internal resources (mother's attachment style, mental health, sociodemographic characteristics), external resources (perceived maternal grandmother's support, mother's marital adaptation), and features of the event itself (infant temperament, additional stressful life events, mother's feelings toward her baby or babies) in proximity to the birth, to personal growth 1 year following the birth. Although mothers of preterm twins reported the highest level of negative feelings toward their infants and the lowest level of mental health, they also experienced the greatest personal growth. Younger age and lower level of education, along with higher perceived support from maternal grandmothers contributed to higher personal growth. It seems that in the wake of stress, even mothers who display lower personal resources can rely on their environmental resources and experience personal growth. PMID- 20307024 TI - Gout is an independent risk factor for MI in women. PMID- 20307025 TI - Leprosy in 1910. 1910. PMID- 20307026 TI - Advances in the diagnosis and treatment of prostate cancer. AB - Prostate cancer is currently diagnosed in more than 34,000 men every year and claims more than 10,000 lives per annum in the UK. Recently, prostate specific antigen (PSA) population screening has been evaluated in two major randomised, controlled studies. Even though the more mature European study confirmed that PSA screening is capable of reducing prostate cancer mortality, anxieties still persist, particularly surrounding the issue of overdiagnosis of clinically insignificant cancer. The recent identification of 29 genetic variants that predispose towards prostate cancer offers another, more targeted, opportunity to reduce mortality. It also raises the possibility of the identification of a sub group of men who are especially susceptible to prostate cancer. In lower-risk patients with localised cancer active surveillance may be sufficient. In fitter men, with more clinically significant disease, eradication of the cancer by surgical removal of the gland is often involved. This is the only treatment which has been proven in a randomised controlled trial to reduce the rate of metastases and mortality compared with watchful waiting. Metastatic prostate cancer is associated with high mortality--approximately 70% within 5 years. Androgen deprivation, which has become the mainstay of treatment, effectively lowers intraprostatic DHT by more than 80%, resulting in reduced androgen receptor stimulation and increased prostate cancer apoptosis. PMID- 20307027 TI - Diagnosing urological disorders in ageing men. AB - The prevalence of erectile dysfunction (ED) increases with age. ED has organic aetiologies and is associated with other clinical comorbidities. Men with ED are more likely to have: cardiac disease, diabetes, hypercholesterolaemia, angina, hypertension, prostate disease and depression. Similarly, men with these conditions are more likely to have ED. It is believed that vasculogenic ED shares a common aetiology with coronary artery disease, including hyperlipidaemia, diabetes and hypertension. Taking a careful history of onset, duration and associated symptoms may reveal possible causes of ED. Past medical history, disease control, trauma and medication use can provide vital information. ED patients with a sedentary lifestyle should be encouraged to exercise. In obese men, weight loss of 10% or more can improve IIEF score. Regular exercise, healthy diet, smoking cessation, limiting alcohol intake and avoiding recreational drugs can reduce the risk of, or improve, ED. It is important to differentiate between patients suffering from nocturnal frequency, enuresis or nocturnal polyuria as the causes and treatments for each of these conditions are different. Reducing fluid intake after 6 pm and avoiding alcohol and/or caffeine at night may reduce nocturnal voiding. Anticholinergics can decrease bladder overactivity. An improvement in nocturia and nocturia bother score have been shown after administration of oral melatonin. Nocturnal enuresis can often be the only symptom of high-pressure chronic retention which is prevalent in older men. It is important to recognise this condition as treatment can prevent further renal impairment. In nocturnal polyuria the urine output at night is more than a third of the total daily urine output. If conservative measures are not successful, in the absence of heart failure, a low-dose diuretic in the afternoon can help the kidneys get rid of the fluid before bedtime. PMID- 20307028 TI - GPs have pivotal role in care of stroke patients. AB - Stroke is a major cause of mortality in the community and the most common cause of disability. At one year, a third of patients who have had a stroke have died, and 37% of survivors are dependent. In the acute phase of ischaemic stroke, patients should receive thrombolysis (within 4.5 hours of stroke onset), aspirin (within 48 hours of onset), and early access to a stroke unit. Care in a stroke unit significantly reduces the risk of death or dependency irrespective of stroke severity. A multidisciplinary team to manage the range of problems after stroke (e.g. swallowing difficulties, communication problems, mobility) is central to rehabilitation. Much rehabilitation is orientated toward physical function whereas returning to their social roles is more important to patients. While the emphasis of rehabilitation is on targeted therapy interventions to improve function and finding compensatory strategies to increase independence--the goal of community exercise is to improve general physical fitness and activity levels. The marked loss of physical fitness evident in stroke survivors can be at least partly reversed by physical fitness training, and leads to improvements in physical function. Group exercise also improves self-confidence and social integration. Pharmacological therapies play a key role in secondary prevention, and must be started as soon as possible to reduce the risk of early recurrence. PMID- 20307029 TI - Scalp problems. PMID- 20307031 TI - Surgical management of vitreofoveal traction syndrome: optical coherence tomographic evaluation and clinical outcomes. AB - BACKGROUND AND OBJECTIVE: To characterize vitreofoveal traction syndrome and to correlate clinical observations, optical coherence tomography features, and surgical results. PATIENTS AND METHODS: A retrospective, consecutive, interventional case series of 36 patients. Clinical and optical coherence tomography features taken from patient charts were compared preoperatively and postoperatively and correlated with visual outcomes. RESULTS: Preoperatively, visual acuity ranged from 20/40 to 20/400 and improved more than 2 lines in 50% of eyes. A macular hole developed in 2 eyes. The optical coherence tomography appearance of traction resolved in all eyes; cystic change improved markedly or resolved in 86% of eyes. Preoperative optical coherence tomography features did not correlate with visual acuity. Patients with symptoms for less than a 6-month duration (P = .048) were more likely to obtain a visual acuity of 20/40 or better postoperatively. Presence or resolution of macular cystic changes and subretinal fluid did not correlate with visual acuity or change (P > .05). CONCLUSION: Patients with vitreofoveal traction syndrome usually achieve favorable visual optical coherence tomography outcomes after pars plana vitrectomy. PMID- 20307032 TI - Visual outcomes in five different approaches for treatment of central retinal vein occlusion. AB - BACKGROUND AND OBJECTIVE: Four treatment methods for central retinal vein occlusion were compared with its natural course. PATIENTS AND METHODS: In this partially prospective, comparative, interventional case series on 63 eyes with central retinal vein occlusion, five approaches were compared: intravitreal triamcinolone injection; radial optic neurotomy; combined radial optic neurotomy and intraocular triamcinolone injection; combined internal limiting membrane peeling, radial optic neurotomy, and intraocular triamcinolone; and observation. RESULTS: Final visual acuity in the intravitreal triamcinolone group was better compared with the observation (P = .025), radial optic neurotomy (P = .037), combined radial optic neurotomy/intraocular triamcinolone injection (P = .401), and combined internal limiting membrane peeling, radial optic neurotomy, and intraocular triamcinolone injection (P = .023) groups. However, after adjustment for baseline visual acuity, the only treatment method with significant visual acuity improvement in relation to the observation group was the combined radial optic neurotomy/intraocular triamcinolone injection (P = .025, .023, and .054 at 1, 3, and 6 months, respectively). CONCLUSION: Among the five different approaches analyzed in this study, combined radial optic neurotomy and intraocular triamcinolone injection may provide a better visual outcome in the management of central retinal vein occlusion. PMID- 20307033 TI - Assessing the reliability of automated OCT retinal thickness measurements in patients with choroidal neovascularization due to age-related macular degeneration. AB - BACKGROUND AND OBJECTIVE: To compare automated versus manual retinal measurement using Stratus optical coherence tomography (OCT) (Carl Zeiss Meditec, Dublin, CA) in patients with choroidal neovascularization (CNV) due to age-related macular degeneration (AMD). PATIENTS AND METHODS: Patients with subfoveal CNV due to AMD underwent Stratus OCT imaging. Each scan was evaluated for automated: foveal center point thickness, central subfield thickness, signal strength, and manual: central retinal thickness, central retinal/lesion thickness, CNV thickness, pigment epithelial detachment thickness, and number of correct retinal boundaries (CRBs). RESULTS: A total of 209 OCT visits (49 patients) were assessed. On fast macular thickness map, 52% of scans had less than 4 (of possible 6) CRBs placed by the automated OCT algorithm. There was a mean difference of 34 microm between automated foveal center point thickness and manual central retinal thickness (P < .00005). Only 40% and 27% of automated foveal center point thickness and central subfield, respectively, lay within +/- 25 microm of manual central retinal thickness. As the number of CRBs or signal strength increased, the difference between manual and automated measurements decreased. CONCLUSION: Manual retinal thickness measurements differ significantly from those calculated by the current automated Stratus OCT software in exudative AMD. PMID- 20307034 TI - Association between retinal thickness and retinal pigment epithelium elevation in age-related macular degeneration. AB - BACKGROUND AND OBJECTIVE: To determine the association between retinal pigment epithelium elevation and maximum retinal thickness in patients with age-related macular degeneration. PATIENTS AND METHODS: Fifteen patients (mean age = 76 +/- 8 years) with age-related macular degeneration and pigment epithelial detachment underwent optical coherence tomography. The images were analyzed by two observers to measure maximum retinal thickness and the width and maximum height of the pigment epithelial detachment. Linear regression analysis was performed to determine the association between maximum retinal thickness and retinal pigment epithelium elevation. RESULTS: The results indicated high correlations between observers in identifying pigment epithelial detachment edges and measuring retinal pigment epithelium elevation and maximum retinal thickness. Pigment epithelial detachment height ranged from 82 to 599 microns. Mean maximum retinal thickness was 424 +/- 150 microns. Increased maximum retinal thickness was associated with more elevated retinal pigment epithelium (r = 0.7; P = .003). CONCLUSION: Retinal thickness was associated with pigment epithelial detachment height, warranting future investigations into pathophysiologic mechanisms leading to and potential treatment for pigment epithelial detachment and associated retinal thickening. PMID- 20307035 TI - Ranibizumab for exudative age-related macular degeneration in eyes previously treated with alternative vascular endothelial growth factor inhibitors. AB - BACKGROUND AND OBJECTIVE: To evaluate ranibizumab for exudative age-related macular degeneration previously treated with pegaptanib, bevacizumab, or both. PATIENTS AND METHODS: This was a retrospective, interventional case series of patients with exudative age-related macular degeneration who were treated with ranibizumab after being initially treated with pegaptanib, bevacizumab, or both. The primary outcome was change in visual acuity following the switch to ranibizumab. RESULTS: One hundred two eyes of 92 patients were identified. Following the switch to ranibizumab, there was an average gain of 0.7 lines in visual acuity. Ninety-four eyes (92%) lost 3 or fewer lines, 29 eyes (28%) gained more than 3 lines, and 3 eyes (3%) lost more than 6 lines after switching to ranibizumab. Lesion type and time between previous vascular endothelial growth factor inhibitor and ranibizumab did not affect the response. CONCLUSION: Ranibizumab maintained visual acuity in the majority of patients and appears to be an effective treatment regardless of previous anti-vascular endothelial growth factor therapy. PMID- 20307036 TI - The relation between bevacizumab injection and the formation of subretinal fibrosis in diabetic patients with panretinal photocoagulation. AB - BACKGROUND AND OBJECTIVE: To report the development of subretinal fibrosis after the injection of intravitreal bevacizumab in eyes with proliferative diabetic retinopathy (PDR) refractory to panretinal laser photocoagulation (PRP). PATIENTS AND METHODS: Twenty-one eyes of 15 patients treated with PRP and intravitreal injection of bevacizumab were included in this study. The clinical outcomes of 21 eyes having subretinal fibrosis after intravitreal bevacizumab injection were reviewed. RESULTS: There were 9 men and 6 women with a mean age of 51.3 +/- 8.9 years. All eyes had PDR refractory to panretinal photocoagulation and were treated with at least one intravitreal injection of 1.25 mg of bevacizumab (mean number of injections: 1.8). Before injection, there was subretinal fibrosis in 5 eyes and vitreoretinal traction in 19 eyes. After a mean follow-up period of 7 months, the development or progression of subretinal fibrosis was detected in all eyes. CONCLUSION: Intravitreal injection of bevacizumab may cause formation or progression of subretinal fibrosis in patients with PDR refractory to PRP. PMID- 20307037 TI - Role of ultrasound biomicroscopy in management of eyes with stage 5 retinopathy of prematurity. AB - BACKGROUND AND OBJECTIVE: To assess the role of ultrasound biomicroscopy in the surgical management of eyes with stage 5 retinopathy of prematurity. PATIENTS AND METHODS: Ultrasound biomicroscopy was performed preoperatively in 18 eyes with stage 5 retinopathy of prematurity to view the access to the anterior surgical space. RESULTS: Of the 15 (83.3%) eyes with anterior open funnel on B-scan ultrasonography, only 8 (53.3%) eyes had open access to the anterior surgical space and were scheduled for lensectomy. CONCLUSION: Ultrasound biomicroscopy is an effective tool for assessing anterior surgical space and helps surgical decision making in vitreoretinal surgery in eyes with stage 5 retinopathy of prematurity. PMID- 20307038 TI - Optical coherence tomography imaging of the fovea in retinopathy of prematurity. AB - BACKGROUND AND OBJECTIVE: To report foveal optical coherence tomography (OCT) findings in patients with a history of retinopathy of prematurity (ROP). PATIENTS AND METHODS: In a case-control study, OCT imaging of the fovea was performed on mostly adult patients with a history of ROP and no significant macular pathology. The same OCT imaging was performed on control subjects who were born full-term. RESULTS: Fourteen eyes of 12 patients with ROP were studied. Mean age was 39 years and mean gestational age at birth was 28 weeks. Of the 11 eyes with no cataract or pseudophakia, median best-corrected visual acuity was 20/40. Three eyes with cataracts had visual acuities of 20/50, 20/60, and 20/100. OCT imaging showed that eyes in the ROP group had a relative loss of the foveal depression, increased macular thickness, and continuation of inner retinal layers within the fovea. CONCLUSION: OCT imaging demonstrated abnormal foveal architecture in patients with a history of ROP, but most of these patients maintained good visual acuity. PMID- 20307039 TI - Short-term outcome of bimanual 23-gauge transconjunctival sutureless vitrectomy for patients with complicated vitreoretinopathies. AB - BACKGROUND AND OBJECTIVE: To evaluate the safety and efficacy of bimanual 23 gauge transconjunctival sutureless vitrectomy for patients with complicated vitreoretinopathies. PATIENTS AND METHODS: Twenty-nine eyes of 27 patients that received bimanual 23-gauge transconjunctival sutureless vitrectomy were prospectively enrolled. Fourteen eyes with diabetic tractional retinal detachment, 13 eyes with complicated rhegmatogeneous retinal detachment (including 3 traumatic retinal detachments), and 2 eyes with massive subretinal hemorrhage received 23-gauge transconjunctival sutureless vitrectomy. The visual and anatomical outcomes and the complications were measured. RESULTS: Visual acuity improved from 2.15 +/- 1.03 to 1.24 +/- 1.33 logarithm of the minimum angle of resolution (LogMAR) in the complicated diabetic retinopathy group (P = .002) and from 2.07 +/- 1.17 to 1.09 +/- 1.15 LogMAR in the complicated retinal detachment group (P = .009). Anatomical success was achieved in 23 of 29 (79.3%) eyes after the first vitrectomy and in 27 of 29 (94.6%) eyes after the final procedure. CONCLUSION: The bimanual 23-gauge transconjunctival sutureless vitrectomy was feasible and reproducible in patients with complicated vitreoretinal disease. This technique might provide a safe and effective alternative to the standard 20-gauge vitrectomy for severe complicated cases. PMID- 20307040 TI - Combination of internal limiting membrane peeling and endophotocoagulation for retinal detachment related to high myopia in patients with macular hole. AB - BACKGROUND AND OBJECTIVE: To evaluate the anatomic and visual outcomes of undergoing combined internal limiting membrane peeling and endophotocoagulation in retinal detachment related to high myopia in patients with macular hole. PATIENTS AND METHODS: Fifty-two eyes of 52 consecutive patients with macular hole and retinal detachment related to high myopia were recruited into the study. The combination treatment group underwent vitrectomy and perfluoropropane gas injection with the assistance of indocyanine green internal limiting membrane peeling and additional endophotocoagulation 2 weeks postoperatively. The control group only underwent vitrectomy and perfluoropropane gas injection and was matched to the combination treatment group according to the refractive errors and the size of macular hole. RESULTS: The primary macular hole closure rate was significantly higher in the combination treatment group (96.2%) than in the control group (57.7%) (P < .05). Six months postoperatively, a best-corrected visual acuity improvement of 2 or more lines was found in more eyes in the combination treatment group (100%) than in the control group (53.8%) (P > .05). CONCLUSION: Combined internal limiting membrane peeling and endophotocoagulation for retinal detachment related to high myopia in patients with macular hole has a promising anatomic closure rate and visual acuity and may be a better choice for retinal detachment in this group. PMID- 20307041 TI - Resident-performed Ahmed glaucoma valve surgery. AB - BACKGROUND AND OBJECTIVE: To evaluate the safety and efficacy of residents performing glaucoma valve surgery at a metropolitan county hospital. PATIENTS AND METHODS: A retrospective analysis was performed of consecutive resident-performed Ahmed valve (New World Medical, Inc., Rancho Cucamonga, CA) glaucoma surgeries from 1993 to 2005. Data of 50 eyes of 48 patients were evaluated for intraocular pressure (IOP) and best-corrected visual acuity. RESULTS: The mean follow-up period was 34.7 +/- 30.5 months, with an IOP decrease from 30.8 +/- 11.3 mm Hg preoperatively to 15.3 +/- 11.6 mm Hg at last visit. Success, defined by a postoperative IOP of greater than 5 mm Hg and at most 21 mm Hg or less or a decreased postoperative IOP of at least 25% if the preoperative IOP was already 21 mm Hg or less, occurred in 78% of eyes. Best-corrected visual acuity decreased in 58% of eyes. Four eyes (8%) required subsequent penetrating glaucoma procedures. CONCLUSION: This retrospective study suggests that placement of an Ahmed valve can be a safe and effective procedure in the hands of residents under appropriate attending physician supervision. PMID- 20307042 TI - Does phacoemulsification affect the long-term success of non-penetrating deep sclerectomy? AB - BACKGROUND AND OBJECTIVE: Phaco non-penetrating deep sclerectomy (PhacoNPDS) is an option to simultaneously treat cataract and glaucoma. The authors assessed tensional success of PhacoNPDS and NPDS up to 3 years of follow-up. PATIENTS AND METHODS: A longitudinal consecutive retrospective study was conducted comparing 376 eyes undergoing NPDS (group 1) and 87 eyes undergoing PhacoNPDS (group 2). Success was defined as complete 1 (intraocular pressure [IOP] < 21 mm Hg without medication); complete 2 (at least a 20% reduction of preoperative IOP without medication), and qualified (IOP < 21 mm Hg with or without medication). RESULTS: Preoperative IOP and number of medications were 23.7 and 2.7 in group 1 and 23.1 and 2.6 in group 2, respectively. Postoperative IOP (3 years) was 13.1 mm Hg in group 1 and 13.4 mm Hg in group 2 (P = .000). Complete 1, complete 2, and qualified success in 3 years were 57.5%, 53.7%, and 94.5% in group 1 and 56.1%, 56.1%, and 100% in group 2, respectively (P = .861, .772, and .159). Final number of medications was 0.5 in group 1 and 0.3 in group 2. CONCLUSION: PhacoNPDS seems to achieve similar tensional results as NPDS alone up to 3 years of follow-up. PMID- 20307043 TI - Ultrasound energy in phacoemulsification: a comparative analysis of phaco-chop and stop-and-chop techniques according to the degree of nuclear density. AB - BACKGROUND AND OBJECTIVE: To evaluate the amount of ultrasound energy used, corneal endothelial cell loss, and central corneal thickness using the phaco-chop and stop-and-chop techniques for cataracts with different degrees of nuclear density. PATIENTS AND METHODS: One hundred two eyes of 51 patients with bilateral senile cataract were included. Each eye was randomly assigned to have either phaco-chop or stop-and-chop nucleofractis during phacoemulsification. The groups were divided into two subgroups according to the nuclear density. The effective phacoemulsification time, endothelial cell density, and central corneal thickness were analyzed. RESULTS: The mean effective phacoemulsification time was similar between the groups in moderately dense nuclei (2.17 +/- 1.33 vs 1.33 +/- 1.05 seconds; P = .41). However, the phaco-chop technique required less effective phacoemulsification time than the stop-and-chop technique in dense nuclei (3.86 +/- 4.18 vs 6.70 +/- 5.43 seconds; P = .01). The endothelial cell loss and the central corneal thickness did not vary significantly between the groups. CONCLUSION: The phaco-chop technique requires lower ultrasound energy for nuclear management than the stop-and-chop technique in dense cataracts and the resulting endothelial loss was similar in both techniques. PMID- 20307044 TI - Femtosecond LASIK combined with astigmatic keratotomy for the correction of refractive errors after penetrating keratoplasty. AB - BACKGROUND AND OBJECTIVE: To evaluate the outcomes of femtosecond laser in situ keratomileusis (LASIK) compared to combined LASIK and astigmatic keratotomy in the treatment of refractive errors following penetrating keratoplasty. PATIENTS AND METHODS: A retrospective review was performed on 18 eyes of 16 patients who underwent LASIK for visual rehabilitation after penetrating keratoplasty. Seven eyes (38.8%) had undergone paired relaxing incisions with topographic guidance prior to LASIK performance. RESULTS: Preoperative uncorrected visual acuity was 20/100 or worse in 13 eyes (72.2%) and best-corrected visual acuity (BCVA) was 20/40 or better in 15 eyes (83.3%). After LASIK, uncorrected visual acuity was 20/40 or better in 10 eyes (55.5%) and BCVA was 20/40 or better in 17 eyes (94.4%). Three eyes (16.6%) had a loss of 1 to 2 lines of BCVA. No difference in visual outcomes was noted in eyes undergoing LASIK and astigmatic keratotomy versus LASIK alone. An increased complication rate was noted in patients who also underwent astigmatic keratotomy and was associated with flap creation. CONCLUSION: Femtosecond LASIK is effective in reducing ametropia after penetrating keratoplasty. Astigmatic keratotomy might complicate flap creation in LASIK; therefore, photorefractive keratectomy should be considered for patients who had previous astigmatic keratotomy to reduce astigmatism. PMID- 20307045 TI - Intraoperative use of three-dimensional spectral-domain optical coherence tomography. AB - BACKGROUND AND OBJECTIVE: To develop a prototype three-dimensional anterior segment spectral-domain optical coherence tomography (SD-OCT) device and demonstrate the feasibility of its use in the operating room. PATIENTS AND METHODS: Single-institution interventional case series including six consecutive patients undergoing Descemet's stripping automated endothelial keratoplasty (DSAEK). The prototype anterior segment SD-OCT was used intraoperatively to search for the presence of interface fluid between the host cornea and the DSAEK graft. RESULTS: Anterior segment SD-OCT was successfully used intraoperatively during DSAEK. After the initial placement of the graft, no fluid was clinically apparent; however, interface fluid was identified by anterior segment SD-OCT in two of the six cases. After additional aspiration, all patients were fluid-free on follow-up anterior segment SD-OCT scanning. CONCLUSION: Intraoperative anterior segment SD-OCT was used successfully to find interface fluid that was clinically undetectable under the microscope. As such, all patients were able to leave the operating room with a fully attached graft. PMID- 20307046 TI - The effect of femtosecond laser lamellar dissection at various depths on corneal endothelium in the recipient bed of the porcine eye. AB - BACKGROUND AND OBJECTIVE: To evaluate the effect of femtosecond laser lamellar dissection on corneal endothelium ultrastructure and viability. MATERIALS AND METHODS: Newly enucleated porcine eyes (N = 32) were used. The eyes were divided into four groups and a 7.5-mm diameter corneal lamellar dissection with the same size side cut at various depths was performed using a 60-kHz femtosecond laser with raster and spiral lamellar pattern. The endothelium was examined using scanning electron microscopy and light microscopy with Alizarin red staining. RESULTS: All four groups showed similar corneal endothelial cell morphology and viability at the center of the endothelium regardless of the lamellar cut pattern (P > .05). In groups 2 and 3, linear dotted endothelial cell damage or folding correlating with the side cut was observed. CONCLUSION: Using femtosecond lasers for stromal dissection and side cutting was safe for the central endothelium and caused only minimal damage to the peripheral endothelium, regardless of the laser emission pattern. PMID- 20307047 TI - A rabbit model of conjunctival injection induction after strabismus surgery enhanced by topical application of irritant chemicals. AB - BACKGROUND AND OBJECTIVE: To establish a rabbit model of conjunctival injection after strabismus surgery. MATERIALS AND METHODS: A prospective, masked-observer, controlled study was performed. Twenty eyes of 20 rabbits underwent strabismus surgery. Fifteen eyes were treated with 90% ethanol for 5 minutes followed by dispase for 10 minutes and 5 eyes were treated with balanced salt solution as a control group. Injection severity was assessed by means of a grade (0 to 3) at 5 minutes, 1, 24, and 48 hours, and 1 week after surgery. RESULTS: The application of 90% ethanol for 5 minutes followed by dispase for 10 minutes reliably caused conjunctival injection in all of the rabbits and the injection scores were significantly higher than those of the control group at 24 (P = .008) and 48 (P = .001) hours and 1 week (P = .022) after surgery. CONCLUSION: The combined application of 90% ethanol and dispase in rabbit eyes was found to successfully create a conjunctival injection rabbit model after strabismus surgery. PMID- 20307048 TI - In situ intraocular suture techniques for pupilloplasty and suspension of a subluxated intraocular lens. AB - The modified McCannel and Siepser techniques allow surgeons to create a locking knot at the extraocular space to maintain a closed chamber. The authors demonstrate that this method made the pupilloplasty easy and applied it to suspend a subluxated intraocular lens with scleral fixation of haptics. PMID- 20307049 TI - Transscleral fixation by injector implantation of a foldable intraocular lens. AB - Scleral fixation of a foldable intraocular lens (IOL) was performed in 17 eyes of 17 patients using a new small incision technique with injector implantation. All eyes were implanted with a hydrophobic acrylic three-piece IOL, either with phacoemulsification surgery or secondarily. No cases of intraoperative or postoperative complications were observed. The operation time required for scleral fixation only was less than 30 minutes in all cases. Scleral fixation of foldable IOLs using a self-sealing tunnel incision and injector technique minimizes intraoperative hypotony and related complications such as suprachoroidal hemorrhage. Furthermore, this technique saves surgery time and the sutureless technique used for most patients can reduce postoperative astigmatism. PMID- 20307050 TI - High-definition slit-lamp video camera system. AB - Using a high-definition video camera for slit-lamp examination is now possible with the assistance of an adaptor. The authors describe the easy manipulation, convenience of use, and performance of a high-definition slit-lamp video camera system and provide images of eyes that were obtained using the system. PMID- 20307051 TI - A computer algorithm to quantitatively assess quality of digital optic disc images. AB - Optic disc photography is used in the management and study of glaucoma. Quality assessment is needed at the time of acquisition and during review. A computerized algorithm for objective quality assessment was developed to mimic the procedure used by human observers. It was tested on film-based images obtained with mydriasis (40 normal and 46 glaucomatous eyes) and non-mydriatic digital images (30 normal and 38 glaucomatous eyes). The image sharpness was graded by six masked readers into four categories. The area under the receiver operating characteristic curve for identifying unreadable images was 1.0 for the digital and film-based images and 0.91 and 1.0 for differentiating between unreadable and mediocre images for digital and film-based images, respectively. This pilot study demonstrates that the algorithm can identify all unreadable images. Further studies are necessary to test whether it can be applied to images obtained in other locations on the fundus and with additional cameras. PMID- 20307052 TI - Increasing the sensitivity of enzyme-linked immunosorbent assay using multiplexed electrokinetic concentrator. AB - We developed a novel method to increase the sensitivity of standard enzyme-linked immunosorbent assay (ELISA) using a multiplexed electrokinetic concentration chip. The poly(dimethylsiloxane) (PDMS) molecular concentrator (1) was used to trap and collect charged fluorescent product of target-bound enzyme turnover reaction of ELISA that occurred in a standard 96 well plate. Detection sensitivities of both prostate specific antigen (PSA) and CA 19-9 (a human pancreatic and gastrointestinal cancer marker) ELISAs in serum are enhanced approximately 100 fold with a low CV of <17%. We also integrated this method with an on-chip bead-based ELISA that lends itself toward a fully automated on-chip diagnostic device. Detection sensitivity of microfluidic bead-based CA 19-9 ELISA in serum is enhanced approximately 65 fold compared to the results without the electrokinetic accumulation step. This chip can be directly applied to enhance the readout sensitivity of a wide range of existing ELISA kits at concentrations below the current detection limit. PMID- 20307053 TI - Formation of unsymmetrical 1,4-enediones via a focusing domino strategy: cross coupling of 1,3-dicarbonyl compounds and methyl ketones or terminal aryl alkenes. AB - A highly efficient synthesis of unsymmetrical 1,4-enediones from 1,3-dicarbonyl compounds and methyl ketones or terminal aryl alkenes has been developed via a focusing domino strategy. Simple and readily available starting materials, mild reaction conditions, and a very simple operation are advantages of the reaction, which allow straightforward synthesis of a variety of unsymmetrical 1,4 enediones. PMID- 20307054 TI - Hybrid orbital deformation (HOD) effect and spectral red-shift property of nonplanar porphyrin. AB - A series of 5,15-meso,meso-strapped nonplanar porphyrins with different degrees of ruffling distortion, as a model system, have been synthesized and characterized. The spectral red-shift of the nonplanar porphyrins was experimentally demonstrated to mainly originate from the hybrid orbital deformation (HOD) effect due to the distortion in the tetrapyrrole macrocycle, which confirmed previous explanations to the red-shift phenomenon. PMID- 20307055 TI - Multicomponent (n >or= 3) sorption isotherms in reversed-phase liquid chromatography: the effect of immobilized eluent on the retention of analytes. AB - The experimental technique of tracer pulse chromatography was used to simultaneously measure the uptake of eluent components by a C(18)-bonded reversed phase liquid chromatography (RPLC) packing and the retention factors for a series of test analytes over the full range of eluent composition for methanol and acetonitrile with water. The primary objective of the research was to determine whether or not the uptake of eluent components immobilized as part of the stationary phase would influence the retention of analyte standards. Both acetonitrile and methanol were absorbed in or adsorbed on the C(18)-bonded phase with the maximum amount of acetonitrile sorbed being about four times that of methanol. The thermodynamic void volume of the column and the excess sorption isotherms of acetonitrile, methanol, and water in binary aqueous/organic mixtures were determined directly from the tracer pulse experiments. The absolute sorption isotherms of the eluent components were indirectly estimated by a combination of techniques. Regression analysis of the nonstationary inflection point of the excess isotherms provided an estimate of the volume of eluent sorbed by the stationary phase but only over a limited eluent composition range. In order to expand the applicable composition range, several commonly used "unretained" probe solutes were tested to determine the accuracy of the assumption that the retention volumes of these solutes provided a viable measure of the kinetic void volume (mobile-phase volume) of the column. The difference between the thermodynamic and kinetic void volumes provided an estimate of the absolute volume of eluent present in the stationary phase. The experimental results showed that some solutes, viz., water and thiourea, did provide an accurate measure of the mobile-phase volume but only over a limited range of eluent composition. Using deuterated water as the unretained dead time marker for water-rich eluents combined with the regression results from excess isotherm data, the absolute volume of eluent sorbed by the stationary phase could be estimated over the full range of eluent composition. The effect of this uptake of eluent on the retention of the test solutes appeared to be minimal for this particular set of test analytes. PMID- 20307058 TI - Density functional study of hydrogen binding on gold and silver-gold clusters. AB - A theoretical study was carried out on the binding of hydrogen on small bimetallic Ag(m)Au(n) (m + n < or = 5) and pure Au(n) (n < or = 5) clusters with neutral, negative, and positive charge state. It is found that the composition and charge state of clusters have strong influence on the most favorable binding site. The adiabatic ionization potentials, electron affinities, and hydrogen binding energies of cluster hydrides increase with the Au content increasing for the given cluster size. The cationic silver-gold cluster hydrides prefer ejection of Au-containing products whereas the anionic silver-gold cluster hydrides prefer ejection of Ag-containing products. The magnitude of metal-H frequency in combination with the metal-H bond length indicates that, with the same type of the binding site, the Au-H interaction is stronger than the Ag-H interaction. PMID- 20307057 TI - Function of phenylalanine 259 and threonine 314 within the substrate binding pocket of the juvenile hormone esterase of Manduca sexta. AB - Juvenile hormone (JH) is a key insect developmental hormone that is found at low nanomolar levels in larval insects. The methyl ester of JH is hydrolyzed in many insects by an esterase that shows high specificity for JH. We have previously determined a crystal structure of the JH esterase (JHE) of the tobacco hornworm Manduca sexta (MsJHE) [Wogulis, M., Wheelock, C. E., Kamita, S. G., Hinton, A. C., Whetstone, P. A., Hammock, B. D., and Wilson, D. K. (2006) Biochemistry 45, 4045-4057]. Our molecular modeling indicates that JH fits very tightly within the substrate binding pocket of MsJHE. This tight fit places two noncatalytic amino acid residues, Phe-259 and Thr-314, within the appropriate distance and geometry to potentially interact with the alpha,beta-unsaturated ester and epoxide, respectively, of JH. These residues are highly conserved in numerous biologically active JHEs. Kinetic analyses of mutants of Phe-259 or Thr-314 indicate that these residues contribute to the low K(M) that MsJHE shows for JH. This low K(M), however, comes at the cost of reduced substrate turnover. Neither nucleophilic attack of the resonance-stabilized ester by the catalytic serine nor the availability of a water molecule for attack of the acyl-enzyme intermediate appears to be a rate-determining step in the hydrolysis of JH by MsJHE. We hypothesize that the release of the JH acid metabolite from the substrate binding pocket limits the catalytic cycle. Our findings also demonstrate that chemical bond strength does not necessarily correlate with how reactive the bond will be to metabolism. PMID- 20307059 TI - Conformational control of TT dimerization in DNA conjugates. A molecular dynamics study. AB - The paper presents quantum yield results for the [2+2] and 6-4 photodimerization of TT steps in several DNA structures, including hairpins where the context dependence of the photodimerization yield is determined, and it develops a theoretical model that correctly describes the trends in dimerization yield with DNA structure. The DNA conjugates considered include dT(20), dA(20)dT(20), and three alkane-linked hairpins that contain a single TT step. The theoretical modeling of the [2+2] process is based on CASSCF electronic structure calculations for ethylene + ethylene, which show that photoexcitation of low lying excited states leads to potential surfaces that correlate without significant barriers to a conical intersection with the ground state surface at geometries close to the dimer structure. The primary constraint on dimerization is the distance d between the two double bonds, and it is found that d < 3.52 A leads to quantum yield trends that match the observed trends within a factor of 3. Constraints on the dihedral angle between the two double bonds are not as important, and although it is possible to generate better dimerization yield predictions for some structures by including these constraints, the best overall picture is obtained with no constraint. For 6-4 dimerization, a distance g < 2.87 A and no constraint on dihedral angle provide an accurate description of the yield. PMID- 20307060 TI - Mesoporous hydrogels: revealing reversible porosity by cryoporometry, X-ray scattering, and gas adsorption. AB - Mesoporous poly(2-hydroxyethyl methacrylate-co-ethylene glycol dimethacrylate) networks, with cross-linker contents ranging from 100 to 5 mol %, were prepared using a hard-templating approach. The imbibition of the silica pellets with a monomer/cross-linker mixture resulted in mesoporous gels with a pore size of approximately 10 nm, which corresponds well with the average size of the fumed silica particles (10-11 nm). The highly cross-linked materials showed permanent surface areas of up to 230 m(2) g(-1) and porosities up to approximately 33 vol %. The porosity of the hydrogels was investigated in both dry and water-saturated state by nitrogen sorption, cryoporometry, and small-angle X-ray scattering (SAXS). It is only polymeric materials that contain 50 mol % or more of the cross linker that showed a significant porosity after evaporative drying. Freeze-drying is able to preserve the porosity also for hydrogels of intermediate cross-linker content, but the pores of the materials of low cross-linker content collapses completely upon solvent removal. The observed critical cross-linker ratio for pore stability compared favorably with a simple estimate of the critical cross linker density needed to make the material sufficiently stiff to withstand the Laplace pressure during solvent removal. Analysis of the hydrogels in the water swollen state revealed that gels having cross-linker contents down to 5 mol % still possessed mesoporosity. The pores got less defined at very low cross-linker contents, while their size was rather constant at intermediate to high cross linking densities. Closed pores could be reopened upon swelling, which suggests that the observed pore collapse upon drying may be at least partly reversible. PMID- 20307061 TI - Evaluation of the BET method for determining surface areas of MOFs and zeolites that contain ultra-micropores. AB - The BET analysis is commonly used for determining surface areas of metal-organic frameworks (MOFs) and zeolites that contain "ultra-micropores" (<7 A) even though it is often stated that the BET surface areas obtained for such small pores are not really meaningful in an absolute sense. In this study, nitrogen and argon isotherms in MOFs and zeolites (most of them having ultra-micropores) were predicted by grand canonical Monte Carlo (GCMC) simulations and used as pseudoexperimental data to evaluate the BET method for these structures. The BET surface areas calculated from the simulated nitrogen and argon isotherms agree well with the accessible surface areas obtained directly from crystal structures in a geometric fashion. However, this was only true when the BET analysis was performed using the appropriate pressure range based on published "consistency criteria"; the BET analysis underestimates the surface areas of all the selected MOFs and zeolites if it is done in the "standard" BET pressure range. Moreover, the BET theory was shown to work well for a zeolite with a highly heterogeneous surface. These results validate the application of the BET method for determining surface areas of MOFs and zeolites even for materials having ultra-micropores or heterogeneous pores. PMID- 20307062 TI - Spectroscopic rationale for efficient stimulated-emission depletion microscopy fluorophores. AB - We report a rationale for identifying superior dyes for stimulated-emission depletion (STED) microscopy. We compared the dyes pPDI and pTDI, which displayed excellent photostability in single-molecule spectroscopy. Surprisingly, their photostability and performance in STED microscopy differed significantly. While single pTDI molecules could be visualized with excellent resolution (35 nm), pPDI molecules bleached rapidly under similar conditions. Femtosecond transient absorption measurements proved that the overlap between the stimulated-emission band and the excited-state absorption band is the main reason for the observed difference. Thus, assessment of the excited-state absorption band provides a rational means of dye selection and determination of the optimal wavelength for STED. PMID- 20307064 TI - An STM study of the pH dependent redox activity of a two-dimensional hydrogen bonding porphyrin network at an electrochemical interface. AB - Studying electron transfer reactions of porphyrin molecules is important for a wide range of applications including biology, molecular devices, artificial photosynthesis, information storage, and fuel cells. It is known that porphyrins adsorbed in a self-assembled monolayer at an electrochemical interface may lose their electrochemical activity. However, the mechanism of the suppressed electrochemical activity is not clear. In this article, the electrochemical behavior of the two-dimensional network structures of 5,10,15,20-tetrakis(4 carboxylphenyl)-21H,23H-porphyrin (TCPP) molecules, formed via intermolecular hydrogen bonding on Au(111), was investigated by electrochemical scanning tunneling microscopy (EC-STM). Three types of domains, including a square network with molecules trapped inside, square packing, and hexagonal close-packing structures have been observed under various pH conditions. The difference in STM contrast between oxidized and reduced TCPP allows the slow electrochemical reduction of adsorbed TCPP to be visualized by STM. For the first time, the pH dependent reduction of porphyrins was imaged by EC-STM, revealing the mechanism of porphyrin slow reduction at electrochemical interfaces. TCPP reduction can be accelerated either by tuning the working electrode potential to a more negative value or by lowering the H(+) concentration. A redox reaction model was proposed based on the pH dependent reduction of TCPP to elucidate the fundamental aspects of porphyrin redox reactions. PMID- 20307063 TI - Discovery of novel 6,6-heterocycles as transient receptor potential vanilloid (TRPV1) antagonists. AB - The transient receptor potential cation channel, subfamily V, member 1 (TRPV1) is a nonselective cation channel that can be activated by a wide range of noxious stimuli, including capsaicin, acid, and heat. Blockade of TRPV1 activation by selective antagonists is under investigation in an attempt to identify novel agents for pain treatment. The design and synthesis of a series of novel TRPV1 antagonists with a variety of different 6,6-heterocyclic cores is described, and an extensive evaluation of the pharmacological and pharmacokinetic properties of a number of these compounds is reported. For example, the 1,8-naphthyridine 52 was characterized as an orally bioavailable and brain penetrant TRPV1 antagonist. In vivo, 52 fully reversed carrageenan-induced thermal hyperalgesia (CITH) in rats and dose-dependently potently reduced complete Freund's adjuvant (CFA) induced chronic inflammatory pain after oral administration. PMID- 20307065 TI - The significance of 2-furyl ring substitution with a 2-(para-substituted) aryl group in a new series of pyrazolo-triazolo-pyrimidines as potent and highly selective hA(3) adenosine receptors antagonists: new insights into structure affinity relationship and receptor-antagonist recognition. AB - Among the heterocyclic structures identified as potent human A(3) (hA(3)) adenosine receptor's antagonists, we have demonstrated that the new pyrazolo triazolo-pyrimidines, bearing an aryl group in replacement of the C(2)-furyl ring, not only confer a good pharmacological profile (with significantly enhanced selectivity against other adenosine receptor subytpes) but also overcome the metabolic transformation of the furan ring into toxic intermediates. All the synthesized [2-(para-substituted) phenyl]-pyrazolo-triazolo-pyrimidines showed affinity at the hA(3) receptor in the low nanomolar range. The most potent derivative of the series presented better affinity and excellent selectivity (compound 31, K(i) hA(3) = 0.108 nM; hA(1)/hA(3) = 5200; hA(2A)/hA(3) = 7200), in comparison to the C(2)-furyl counterpart. A receptor-driven molecular modeling investigation, based on a recently proposed model of A(3) receptor derived from the crystallographic structure of human A(2A) receptor, has been carried out in order to support the experimental binding data and to justify the enhanced selectivity against the other receptor subtypes. PMID- 20307066 TI - Cationic palladium(II) catalysis: C-H activation/Suzuki-Miyaura couplings at room temperature. AB - Cationic palladium(II) catalyst realized facile C-H activation of aryl urea with arylboronic acids at room temperature. This reaction is extremely mild to carry out aromatic C-H activations through electrophilic substitution. PMID- 20307067 TI - Directed self-assembly of dipeptides to form ultrathin hydrogel membranes. AB - The dipeptide amphiphile Fmoc-Leu-Gly-OH has been induced to self-assemble into thin surface-supported hydrogel gel films and gap-spanning hydrogel membranes. The thickness can be closely controlled, giving films/membranes from tens of nanometers to millimeters thick. SEM and TEM have confirmed that the dipeptides self-assemble to form fibers, with the membranes resembling a dense "mat" of entangled fibers. The films and membranes were stable once formed. The films could be reversibly dried and collapsed, then reswollen to regain the gel structure. PMID- 20307068 TI - Pterin-centered radical as a mechanistic probe of the second step of nitric oxide synthase. AB - The enzyme nitric oxide synthase is both medically relevant and of particular interest from a basic sciences perspective due to the complex nature of the chemical mechanism used to generate NO. The enzyme utilizes multiple redox-active cofactors and substrates to catalyze the five-electron oxidation of substrate l arginine to citrulline and nitric oxide. Two flavins, a cysteine-coordinated heme cofactor and, uniquely, a tetrahydrobiopterin cofactor, are used to deliver electrons from the cosubstrate NADPH to molecular oxygen, analogous to other P450s. The unprecedented involvement of the pterin cofactor as a single electron donor is unique among P450s and pterin utilizing proteins alike and adds to the complexity of this enzyme. In this report, the peroxide shunt with both Mn- and Fe-containing heme domain constructs of iNOS(heme) was used to characterize the formation of HNO as the initial inorganic product produced when oxygen activation occurs without pterin radical formation. To recover NO formation, preturnover of the iron-containing enzyme with l-arginine was used to generate the pterin centered radical, followed by peroxide shunt chemistry. Comparison of NO produced by this reaction with reactions that do not undergo preturnover, do not have peroxide added, or are performed with a pterin unable to generate a radical shows NO production to be dependent on both a pterin-centered radical and activated oxygen. Finally, the chemical HNO donor, Angeli's salt, was used to form the ferrous nitrosyl in the presence of the pterin radical intermediate. Under these conditions, the rate of pterin radical decay was increased as monitored by EPR spectroscopy. In comparison to pterin that aerobically decays, the Angeli's salt treated sample is also significantly protected from oxidation, suggesting ferrous nitrosyl-mediated reduction of the radical. Taken together, these results support a dual redox cycling role for the pterin cofactor during NOS turnover of NHA with particular importance for the proper release of NO from a proposed ferrous nitrosyl intermediate. PMID- 20307069 TI - Efficient electron transfer and sensitizer regeneration in stable pi-extended tetrathiafulvalene-sensitized solar cells. AB - The development of metal-free organic sensitizers is a key issue in dye sensitized solar cell research. We report successful photovoltaic conversion with a new class of stable tetrathiafulvalene derivatives, showing surprising electrochemical and kinetic properties. With time-resolved spectroscopy we could observe highly efficient regeneration of the photo-oxidized tetrathiafulvalene sensitizers, which were attached to a mesoporous TiO(2) film, by a redox mediator in the pores (iodide/tri-iodide), even though the measured driving force for regeneration was only approximately 150 mV. This important proof-of-concept shows that sensitizers with a small driving force, i.e. the oxidation potential of the sensitizer is separated from the redox potenial of the mediator by as little as 150 mV, can operate functionally in dye-sensitized solar cells and eventually aid to reduce photovoltage losses due to poor energetic alignment of the materials. PMID- 20307071 TI - Calcium-induced structural transitions of the calmodulin-melittin system studied by electrospray mass spectrometry: conformational subpopulations and metal unsaturated intermediates. AB - Calmodulin (CaM) is a calcium-sensing protein that can bind to and activate various target enzymes. Here, electrospray ionization mass spectrometry (ESI-MS) was used to investigate calcium-induced structural changes of CaM, as well as binding to the model target melittin (Mel). Nonspecific metalation artifacts were eliminated by conducting the experiments in negative ion mode and with calcium tartrate as metal source [Pan et al. (2009) Anal. Chem. 81, 5008]. Two coexisting CaM subpopulations can be distinguished on the basis of their ESI charge state distributions, namely, relatively disordered conformers (CaM(D), high charge states) and more tightly folded proteins (CaM(F), low charge states). Calcium titration experiments on isolated CaM reveal that the transition from apo-CaM(D) to Ca(4).CaM(F) proceeds with apparent K(d) values of 10, 14, 30, and 12 microM. In the presence of Mel, a gradual [Ca(2+)] increase results in an overall population shift from apo-CaM(D) to Ca(4).CaM(F).Mel. This transition involves various intermediates, Ca(n).CaM(F).Mel with n = 0, ..., 3, as well as apo CaM(D).Mel. Thus, neither the binding of four Ca(2+) nor the existence of a tightly folded CaM conformation is a prerequisite for target binding. Millisecond time-resolved ESI-MS experiments were conducted to monitor the response of a premixed CaM-Mel solution to a calcium concentration jump, thereby mimicking the conditions encountered in a cellular signaling context. The resulting data suggest that the formation of Ca(4).CaM(F).Mel proceeds along three parallel kinetic pathways: (1) metal binding to CaM(D) followed by formation of a compact protein-target complex, (2) folding of the apoprotein, then target binding, followed by metal complexation, (3) target binding to apo-CaM(D) followed by sequential metal binding. The exact structural properties of the various metal unsaturated CaM species, as well as their physiological roles, remain to be elucidated. PMID- 20307070 TI - Regulation of phenylalanine hydroxylase: conformational changes upon phenylalanine binding detected by hydrogen/deuterium exchange and mass spectrometry. AB - Phenylalanine acts as an allosteric activator of the tetrahydropterin-dependent enzyme phenylalanine hydroxylase. Hydrogen/deuterium exchange monitored by mass spectrometry has been used to gain insight into local conformational changes accompanying activation of rat phenylalanine hydroxylase by phenylalanine. Peptides in the regulatory and catalytic domains that lie in the interface between these two domains show large increases in the extent of deuterium incorporation from solvent in the presence of phenylalanine. In contrast, the effects of phenylalanine on the exchange kinetics of a mutant enzyme lacking the regulatory domain are limited to peptides surrounding the binding site for the amino acid substrate. These results support a model in which the N-terminus of the protein acts as an inhibitory peptide, with phenylalanine binding causing a conformational change in the regulatory domain that alters the interaction between the catalytic and regulatory domains. PMID- 20307072 TI - Royal jelly proteome comparison between A. mellifera ligustica and A. cerana cerana. AB - In this study, we compared royal jelly (RJ) produced by Apis mellifera ligustica and Apis cerana cerana in production, protein profiles, and abundances using proteomic approaches. The RJ proteome was displayed using two-dimensional gel electrophoresis (2DGE), and proteins were identified using MALDI-TOF MS and LC Chip/ESI-QTOF MS. Differences in the RJ proteome between the two bee species were validated using western-blot analysis. RJ production by A. cerana cerana (3.21 +/ 0.43 g) is significantly lower than that of A. mellifera ligustica (80.5 +/- 7.83 g). The 2DGE based MS approach identified 52 and 60 proteins in the RJ of A. mellifera ligustica and A. cerana cerana, respectively. The majority of the identified proteins were major royal jelly proteins (MRJPs). Peroxiredoxin 2540, glutathione S-transferase S1, and MRJP5 were detected only in the RJ of A. mellifera ligustica, and MRJP1 was the most abundant MRJP. In contrast, MRJP7 was found only in the RJ of A. cerana cerana. But, similar to A. mellifera ligustica, MRJP1 was found most abundantly in this case too. In this study, glucose oxidase was identified for the first time in the A. cerana cerana RJ. Comparing the protein levels of MRJP1, 2, 3, 4, and 5 between the two species, they were significantly higher in the RJ of A. mellifera ligustica than in A. cerana cerana. This observation was supported by Western blot analysis using anti-MRJP1, 2, 3 antibodies. The result suggested that A. mellifera ligustica needs more nutrition to nurse the developing larvae and queens as compared to that of A. cerana cerana. This study improved our understanding of protein composition of RJ from Western and Eastern honeybees. RJ produced by A. mellifera ligustica exceeds the RJ from A. cerana cerana both in terms of production and health purposes. PMID- 20307073 TI - Lithium cuprate coupling reactions: evaluation of computational methods for determination of the reaction mechanisms. AB - Several computational methods were evaluated for determining the gas-phase reaction mechanisms of lithium dimethylcuprate and dimethylcuprate anion with chloromethane and vinyl chloride. These methods include the B3LYP and M06 density functional theory (DFT) methods, the unscaled and spin-component-scaled Moller Plesset perturbation theory (MP2, SCS-MP2, and SCSC-MP2), CCSD, and CCSD(T). The reaction of interest is an oxidative addition of the alkyl or vinyl halide to the Cu(I) species, resulting in a Cu(III) intermediate, which undergoes reductive elimination with coupling of the two alkyl fragments. Three possible oxidative addition pathways were examined, a concerted addition to Cu(I), an S(N)2-like reaction of Cu on the alkyl halide, and a radical mechanism. A concerted reductive elimination step was also investigated. PMID- 20307074 TI - Molecular dynamics simulation of 8-oxoguanine containing DNA fragments reveals altered hydration and ion binding patterns. AB - We present results of molecular dynamics (MD) simulations of a double-stranded DNA fragment of sequence 5'-d(CGCGAGTTCGCG)-3' and 3'-d(GCGCTCAAGCGC)-5' in its native form and altered with guanine in the G6/C19 base pair replaced by 8 oxoguanine (8oxoG). DNA was simulated in solution with Na(+) counterions and explicit water molecules. Trajectories were analyzed for radial distribution functions (RDFs), spatial distribution functions (SDFs), residence times, and occupancies, for both water and ions. Structural parameters of DNA fragments were also considered. Particularly, we report sensible differences in the statistical and dynamical behavior of water and ions between the healthy and lesion containing models. Structural features such as sugar-phosphate backbone torsion angles also significantly differ. We conclude that 8oxoG noticeably modifies its close environment and that the observed changes in the vicinity of the lesion site might help the enzymes in charge of cleansing 8oxoG from human DNA to locate the aberration in its intrahelical context. This work supports the existence of a determinant early recognition mode of 8oxoG for hOGG1. PMID- 20307075 TI - Oxidation of atomic gold ions: thermochemistry for the activation of O(2) and N(2)O BY Au(+) ((1)S(0) and (3)D). AB - Reaction of Au(+) ((1)S(0) and (3)D) with O(2) and N(2)O is studied as a function of kinetic energy using guided ion beam tandem mass spectrometry. A flow tube ion source produces Au(+) primarily in its (1)S(0) (5d(10)) electronic ground state level but with some (3)D and perhaps higher lying excited states. The distribution of states can be altered by adding N(2)O, which completely quenches the excited states, or CH(4) to the flow gases. Cross sections as a function of kinetic energy are measured for both neutral reagents and both ground and excited states of Au(+). Formation of AuO(+) is common to both systems with the N(2)O system also exhibiting AuN(2)(+) and AuNO(+) formation. All reactions of Au(+) ((1)S(0)) are observed to be endothermic, whereas the excitation energy available to the (3)D state allows some reactions to be exothermic. Because of the closed shell character of ground state Au(+) ((1)S(0), 5d(10)), the reactivity of these systems is low and has cross sections with onsets and peaks at higher energies than expected from the known thermochemistry but lower than energies expected from impulsive processes. Analyses of the endothermic reaction cross sections yield the 0 K bond dissociation energy (BDE) in eV of D(0)(Au(+)-O) = 1.12 +/- 0.08, D(0)(Au(+)-N(2)) >= 0.30 +/- 0.04, and D(0)(Au(+)-NO) = 0.89 +/- 0.17, values that are all speculative because of the unusual experimental behavior. Combining the AuO(+) BDE measured here with literature data also yields the ionization energy of AuO as 10.38 +/- 0.23 eV. Quantum chemical calculations show reasonable agreement with the experimental bond energies and provide the electronic structures of these species. PMID- 20307076 TI - Detection of Escherichia coli O157:H7 using gold nanoparticle labeling and inductively coupled plasma mass spectrometry. AB - O157:H7 is a serotype of enterohemorrhagic Escherichia coli (EHEC) and one of the major causes of food-borne illness. Protection of food safety against bacterial contamination and rapid diagnosis of infection require simple and fast assays for detection of bacterial pathogens, including E. coli O157:H7. We describe here a rapid and sensitive assay for the E. coli O157:H7 bacteria by using antibody affinity binding, gold nanoparticle (Au NP) labeling, and inductively coupled plasma mass spectrometry (ICPMS) detection. Taking advantage of the signal amplification property of Au NPs and the high sensitivity of ICPMS, the assay was able to detect as few as 500 E. coli O157:H7 cells in 1 mL of sample (500 CFU/mL). Tests with nonpathogenic E. coli (DH5alpha, AlphaTauCC35218, and ATCC25922) showed high specificity of the assay for E. coli O157:H7. Each assay was completed within 40 min. Demonstration of this assay for E. coli O157:H7 suggests its potential for detecting a variety of bacterial pathogens. PMID- 20307077 TI - Jacaranone-derived glucosidic esters from Jacaranda glabra and their activity against Plasmodium falciparum. AB - In a survey of plants from Ecuador with antiprotozoal activity, Jacaranda glabra was found to show promising activity against the Plasmodium falciparum K1 strain. Subsequently, activity-guided isolation of the dichloromethane extract from the leaves of J. glabra afforded four new phenylethanoid glucosides containing jacaranone-type moieties (1-4), named jacaglabrosides A-D. Their chemical structures were identified using NMR spectroscopy and MS techniques. The compounds were found to be active in vitro against the P. falciparum K1 strain (IC(50) 1, 1.02; 2, 0.56; 3, 0.56; and 4, 0.55 microg/mL) and generally possessed a low cytotoxicity toward L-6 cells, with the exception of compound 1 (IC(50) 1, 8.3; 2, >90; 3, 87; and 4, 85 microg/mL). PMID- 20307078 TI - Synthesis, properties, and bishomoaromaticity of the first tetrahalogenated derivative of a 1, 5-diphosphadithiatetrazocine: a combined experimental and computational investigation. AB - The first example of a tetrahalogenated derivative of a diphosphadithiatetrazocine, 1,5-Cl(2)P(NSN)(2)PCl(2) (3), was synthesized by cyclocondensation of a 2:1 mixture of SCl(2) and SO(2)Cl(2) with Cl(2)P(NSiMe(3))N(SiMe(3))(2) in CH(2)Cl(2). The heterocycle 3 was isolated as an orange, moisture-sensitive, thermally labile solid and characterized by mass spectrometry, (31)P NMR, and UV-visible spectroscopy. The low-field (31)P NMR chemical shift (93.7 ppm) is indicative of a cross-ring S-S interaction in the eight-membered P(2)N(4)S(2) ring, and this conclusion is supported by density functional computations. Compound 3 exhibits unusual physical properties compared with those of the known tetraalkyl or aryl derivatives; mild heating (90 degrees C) produces an orange rubbery material. The bishomoaromatic character of the diphosphadithiatetrazocine 1,5-R(2)P(NSN)(2)PR(2) (R = Me, Cl, F) is evinced by the negative nucleus-independent chemical shift (NICS) values, and the through space bishomoconjugation in the eight-membered ring decreases with increasing electronegativity of the substituents attached to the P atoms. PMID- 20307080 TI - Magnetic and conducting properties of new halide-bridged mixed-valence Cu(I) Cu(II) 1D coordination polymers including a hexamethylene dithiocarbamate ligand. AB - New mixed-valence Cu(I)-Cu(II) coordination polymers with one-dimensional, infinite-chain structures, [Cu(I)(2)Cu(II)X(2)(Hm-dtc)(2)(CH(3)CN)(2)](n) [Hm dtc(-) = hexamethylene dithiocarbamate; X = Br(-) (1), I(-) (2)], have been prepared and structurally characterized by X-ray diffraction. These complexes consist of a mononuclear copper(II) unit Cu(II)(Hm-dtc)(2) and dinuclear copper(I) units Cu(I)(2)(CH(3)CN)(2)X(2). Magnetic studies have revealed that these complexes have a relatively strong antiferromagnetic interaction [J = -26.9 cm(-1) (1) and J = -22.2 cm(-1) (2)] between the unpaired electrons of the Cu(II) ions through the dinuclear copper(I) halide unit of Cu(I)(2)X(2) in the chain. The electrical properties of 1 and 2 are investigated using an impedance spectroscopy technique, and it is revealed that these complexes exhibit intriguing semiconducting properties with small activation energies [E(a) = 0.562 eV (1) and E(a) = 0.479 eV (2)]. PMID- 20307081 TI - Distribution of nutrients and antinutrients in milled fractions of chickpea and horse gram: seed coat phenolics and their distinct modes of enzyme inhibition. AB - Milled fractions of chickpea ( Cicer arietinum L.) and horse gram ( Macrotyloma uniflorum L. Verdc.) were evaluated for their nutritional and antinutritional characteristics. Crude protein content of these fractions ranged from 22.6-23.8 g 100(-1) g in cotyledon to 7.3-9.1 g 100(-1) g in seed coat fractions. The fat content of chickpea fractions (1.6-7.8 g 100(-1) g) was higher than that of horse gram fractions (0.6-2.6 g 100(-1) g). Crude fiber content was higher in seed coat fractions of both legumes than embryonic axe and cotyledon fractions. Seed coat fractions had high dietary fiber content (28.2-36.4 g 100(-1) g), made up of mainly insoluble dietary fiber. Most of the phytic acid and oligosaccharides were located in the cotyledon fractions, whereas phenolic compounds in higher concentrations were found in seed coats. Significantly higher concentrations of proteinaceous and phenolic inhibitors of digestive enzymes were found in cotyledon and seed coat fractions, respectively. The kinetic studies, using Michaelis-Menten and Lineweaver-Burk derivations, revealed that seed coat phenolics inhibit alpha-amylase activity by mixed noncompetitive (chickpea) and noncompetitive (horse gram) inhibition mechanisms. In the case of trypsin, chickpea and horse gram seed coat phenolics showed noncompetitive and uncompetitive modes of inhibition, respectively. These results suggest the wide variability in the nutrient and antinutrient composition in different milled fractions of legumes and potential utility of these fractions as ingredients in functional food product development. PMID- 20307079 TI - Polyvalent oligonucleotide iron oxide nanoparticle "click" conjugates. AB - We have utilized the copper-catalyzed azide-alkyne reaction to form a dense monolayer of oligonucleotides on a superparamagnetic nanoparticle core. These particles exhibit the canonical properties of materials densely functionalized with DNA, which can be controlled by modulating the density of oligonucleotides on the surface of the particles. Furthermore, like their Au analogues, these particles can easily cross HeLa (cervical cancer) cell membranes without transfection agents due to their dense DNA shell. Importantly, this approach should be generalizable to other azide-functionalized particles. PMID- 20307082 TI - Glyphosate affects seed composition in glyphosate-resistant soybean. AB - The cultivation of glyphosate-resistant (GR) soybeans has continuously increased worldwide in recent years mainly due to the importance of glyphosate in current weed management systems. However, not much has been done to understand eventual effects of glyphosate application on GR soybean physiology, especially those related to seed composition with potential effects on human health. Two experiments were conducted to evaluate the effects of glyphosate application on GR soybeans compared with its near-isogenic non-GR parental lines. Results of the first experiment showed that glyphosate application resulted in significant decreases in shoot nutrient concentrations, photosynthetic parameters, and biomass production. Similar trends were observed for the second experiment, although glyphosate application significantly altered seed nutrient concentrations and polyunsaturated fatty acid percentages. Glyphosate resulted in significant decreases in polyunsaturated linoleic acid (18:2n-6) (2.3% decrease) and linolenic acid (18:3n-3) (9.6% decrease) and a significant increase in monounsaturated fatty acids 17:1n-7 (30.3% increase) and 18:1n-7 (25% increase). The combined observations of decreased photosynthetic parameters and low nutrient availability in glyphosate-treated plants may explain potential adverse effects of glyphosate in GR soybeans. PMID- 20307084 TI - Enantioselective ProPhenol-catalyzed addition of 1,3-diynes to aldehydes to generate synthetically versatile building blocks and diyne natural products. AB - A highly enantioselective method for the catalytic addition of terminal 1,3 diynes to aldehydes was developed using our dinuclear zinc ProPhenol (1) system. Furthermore, triphenylphosphine oxide was found to interact synergistically with the catalyst to substantially enhance the chiral recognition. The generality of this catalytic transformation was demonstrated with aryl, alpha,beta-unsaturated and saturated aldehydes, of which the latter were previously limited in alkynyl zinc additions. The chiral diynol products are also versatile building blocks that can be readily elaborated; this was illustrated through highly selective trans-hydrosilylations, which enabled the synthesis of a beta-hydroxyketone and enyne. Additionally, the development of this method allowed for the rapid total syntheses of several biologically important diynol-containing natural products. PMID- 20307085 TI - Plasmonic nanobubbles as transient vapor nanobubbles generated around plasmonic nanoparticles. AB - We have used short laser pulses to generate transient vapor nanobubbles around plasmonic nanoparticles. The photothermal, mechanical, and optical properties of such bubbles were found to be different from those of plasmonic nanoparticle and vapor bubbles, as well. This phenomenon was considered as a new complex nanosystem-plasmonic nanobubble (PNB). Mechanical and optical scattering properties of PNB depended upon the nanoparticle surface and heat capacity, clusterization state, and the optical pulse length. The generation of the PNB required much higher laser pulse fluence thresholds than the explosive boiling level and was characterized by the relatively high lower threshold of the minimal size (lifetime) of PNB. Optical scattering by PNB and its diameter (measured as the lifetime) has been varied with the fluence of laser pulse, and this has demonstrated the tunable nature of PNB. PMID- 20307086 TI - Lactonecembranoids from Croton laevigatus. AB - Six new cembranoids, laevigatlactones A-F (1-6), and the known compound neocrotocembraneic acid (7) were isolated from leaves of Croton laevigatus. Their structures were elucidated on the basis of spectroscopic analysis, and that of 1 was confirmed by X-ray crystallography. Compound 2 exhibited modest cytotoxicity against HeLa cells, with an IC(50) value of 38.4 microM. PMID- 20307089 TI - Shape-controlled synthesis of single-crystalline palladium nanocrystals. AB - A versatile method for selectively synthesizing single-crystalline rhombic dodecahedral, cubic, and octahedral palladium nanocrystals, as well as their derivatives with varying degrees of edge- and corner-truncation, was reported for the first time. This is also the first report regarding the synthesis of rhombic dodecahedral palladium nanocrystals. All the nanocrystals were readily synthesized by a seed-mediated method with cetyltrimethylammonium bromide as surfactant, KI as additive, and ascorbic acid as reductant. At the same ascorbic acid concentration, a series of palladium nanocrystals with varying shapes were obtained through manipulation of the concentration of KI and the reaction temperature. The formation of different palladium facets were correlated with their growth conditions. In the absence of KI, the 100 palladium facets are favored. In the presence of KI, the concentration of KI and the reaction temperature play an important role on the formation of different palladium facets. The 110 palladium facets are favored at relatively high temperatures and medium KI concentrations. The 111 palladium facets are favored at relatively low temperatures and medium KI concentrations. The 100 palladium facets are favored at either very low or relatively high KI concentrations. These correlations were explained in terms of surface-energy and growth kinetics. These results provide a basis for gaining mechanistic insights into the growth of well-faceted metal nanostructures. PMID- 20307087 TI - Study on the constituents of Mexican propolis and their cytotoxic activity against PANC-1 human pancreatic cancer cells. AB - Three new flavonoids, (2R,3R)-3,5-dihydroxy-7-methoxyflavanone 3-(2 methyl)butyrate (1), (7''R)-8-[1-(4'-hydroxy-3'-methoxyphenyl)prop-2-en-1 yl]chrysin (2), and (7''R)-8-[1-(4'-hydroxy-3'-methoxyphenyl)prop-2-en-1 yl]galangin (3), together with 41 known compounds (4-44) were isolated from a methanolic extract of Mexican propolis. Compounds 2 and 3 are unique natural flavones containing a 1-phenylallyl moiety. The in vitro preferential cytotoxicity of all the isolates was evaluated against a PANC-1 human pancreatic cell line. Compound 3 displayed the most potent preferential cytotoxicity (PC(50) 4.6 microM) in the nutrient-deprived medium (NDM) and triggered apoptosis-like morphological changes in PANC-1 cells. PMID- 20307090 TI - An Organocatalyzed enantioselective synthesis of (2S,3R,4S)-4-hydroxyisoleucine and its stereoisomers. AB - A concise enantioselective total synthesis of (2S,3R,4S)-4-hydroxyisoleucine and its stereoisomers is described. A key feature of this protocol is a catalytic enantioselective mannich reaction that is either anti- or syn-selective as genesis of chirality. PMID- 20307091 TI - Effect of the electron donor/acceptor orientation on the fluorescence transduction efficiency of the d-PET effect of carbazole-based fluorescent boronic acid sensors. AB - We have synthesized three new carbazole-based fluorescent boronic acid sensors to investigate the fluorescence transduction efficiency of the novel d-PET effect, in which the fluorophore acts as the electron donor and the protonated amine/boronic acid group as the electron acceptor of the photoinduced electron transfer process (PET). Aryl ethynyl groups are attached at the 3,6-position of carbazole (aryl = 4-dimethylaminophenyl for sensor 1 or phenyl for sensor 2). Sensor 3 is without 3,6-substitutions. The phenylboronic acid moiety is attached at the 9-position (N-atom) of the carbazole in these sensors. We found that 1 and 3 are d-PET sensors (fluorophore as the electron donor, supported by DFT/TDDFT calculations), which show diminished emission at acidic pH but intensified emission at neutral/basic pH, which is in stark contrast to the normal a-PET (fluorophore as the electron acceptor) sensors, e.g., 2, which shows intensified emission at acidic pH but diminished emission at neutral pH. The fluorescence modulation efficiency of the d-PET effect of the new sensors, i.e., the emission intensity enhancement upon switching from acidic pH to neutral pH, is up to 10 fold, which is greatly improved compared to our previous d-PET sensors (ca. 3 fold). The efficient d-PET effect of the new sensors is attributed to the proper orientation of the electron donor/acceptor; i.e., the dipole moment and the transition moment (the direction of PET) of the new sensors are oriented in the same direction, and the dipole moment values of the new sensors along the vector direction of the PET are larger than that of the reported d-PET sensors. Selective recognition of alpha-hydroxyl carboxylic acids, such as tartaric acid, was achieved with the d-PET sensors, and a novel fluorescence transduction profile of enhancement/diminishment for chemoselectivity was observed. Herein we propose that the orientation of the electron donor/acceptor may significantly affect the fluorescence modulation efficiency of the PET effect; this discovery will be important for the future design of PET sensors with improved fluorescence transduction efficiencies. PMID- 20307092 TI - Asymmetric intramolecular aldol reactions of substituted 1,7-dicarbonylic compounds. A mechanistic study. AB - The diastereo- and enantioselectivity obtained experimentally by List on the proline-catalyzed intramolecular aldol reaction of substituted 1,7-dicarbonylic compounds was accurately predicted using density functional theory methods at the B3LYP/6-31++G** level. A polarizable continuum model was used to describe solvent effects. The theoretical data agree in good extension with List's experimental results, both in enantioselectivity and diastereoselectivity, and allow for the confirmation of our previous rationalization of the main factors contributing to the reaction selectivity. While the enantioselectivity results from an important electrostatic contact between the forming alkoxyde group and the proline moiety, the calculated diasteroselectivity results from several steric contacts that can be established between the different substituents and from their relative orientation in respect to the ring conformation. However, for dialdehydes that can originate two diastereomeric enamine intermediates, the proline attack and the immonium formation steps can also be of major importance in the rationalization of the final reaction selectivity, as is the case in two of the six studied systems. The obtained data allows for a full rationalization of the known experimental systems as well as for the extrapolation to new ones with variable substitution at the carbonylic chain. PMID- 20307093 TI - New triterpenoids and other constituents from a special microbial-fermented tea Fuzhuan brick tea. AB - Fuzhuan brick tea, a special microbial-fermented tea prepared from the leaves of Camellia sinensis var. sinensis, is a traditional beverage used in China throughout history. Phytochemical investigation of this material led to the identification of three new triterpenoids, 3beta,6alpha,13beta-trihydroxyolean-7 one (1), 3beta-acetoxy-6alpha,13beta-dihydroxyolean-7-one (2), and 3beta-O-(8 hydroxyoctanoyl)-12-oleanene (3), together with 11 known compounds, friedelin (4), beta-amyrone (5), beta-amyrin (6), alpha-spinasterone (7), alpha-spinasterol (8), 22,23-dihydro-alpha-spinasterone (9), 22,23-dihydro-alpha-spinasterol (10), alpha-phytol (11), alpha-tocopherol (12), alpha-tocoquinone (13), and caffeine (14). The structures of 1-13 were determined by spectroscopic and chemical methods. Compounds 1 and 2 are the first two examples of triterpenoids possessing a 6-hydroxy-7-one function. All of the compounds, except 6, 8, 10, 11, and 14, were isolated from tea and Camellia spp. for the first time. The antibacterial activities of 1 were assessed against some enteric pathogenic microbes. Compound 1 showed no cytotoxic activity against A-549, Bel-7402, and HCT-8 cell lines. PMID- 20307094 TI - Development of a direct procedure for the measurement of sulfur isotope variability in beers by MC-ICP-MS. AB - In this work, a multi-collector inductively coupled plasma mass spectrometer (MC ICP-MS) was evaluated for the direct measurement of sulfur stable isotope ratios in beers as a first step toward a general study of the natural isotope variability of sulfur in foods and beverages. Sample preparation consisted of a simple dilution of the beers with 1% (v/v) HNO(3). It was observed that different sulfur isotope ratios were obtained for different dilutions of the same sample indicating that matrix effects affected differently the transmission of the sulfur ions at masses 32, 33, and 34 in the mass spectrometer. Correction for mass bias related matrix effects was evaluated using silicon internal standardization. For that purpose, silicon isotopes at masses 29 and 30 were included in the sulfur cup configuration and the natural silicon content in beers used for internal mass bias correction. It was observed that matrix effects on differential ion transmission could be corrected adequately using silicon internal standardization. The natural isotope variability of sulfur has been evaluated by measuring 26 different beer brands. Measured delta(34)S values ranged from -0.2 to 13.8 per thousand. Typical combined standard uncertainties of the measured delta(34)S values were < or = 2 per thousand. The method has therefore great potential to study sulfur isotope variability in foods and beverages. PMID- 20307095 TI - Cloning, expression, and characterization of a thioredoxin reductase cDNA from Taiwanofungus camphorata. AB - A cDNA encoding putative thioredoxin reductase (TR) was identified from a medicinal mushroom, Taiwanofungus camphorata (T. camphorata). Alignment of the deduced amino acid sequence with TRs from other organisms showed high levels of identity (59-74%). A three-dimensional (3-D) homology structure was created for this TR. Functional T. camphorata TR (TcTR) was overexpressed in yeast and purified. The purified enzyme showed a monomic form on a 10% sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). The enzyme's half-life of deactivation at 60 degrees C was 12.9 min, and its thermal inactivation rate constant K(d) was 5.37 x 10(-2) min(-1). The optimal pH for the enzyme was pH 8 and retained about 76% activity in the presence of 0.1 M imidazole. The enzyme showed 50% activity after 10 min of incubation at 37 degrees C with chymotrypsin. The Michaelis constant (K(m)) value for dithionitrobenzoate (DTNB) was 1.59 mM. PMID- 20307096 TI - Polymeric micelles with ionic cores containing biodegradable cross-links for delivery of chemotherapeutic agents. AB - Novel functional polymeric nanocarriers with ionic cores containing biodegradable cross-links were developed for delivery of chemotherapeutic agents. Block ionomer complexes (BIC) of poly(ethylene oxide)-b-poly(methacylic acid) (PEO-b-PMA) and divalent metal cations (Ca(2+)) were utilized as templates. Disulfide bonds were introduced into the ionic cores by using cystamine as a biodegradable cross linker. The resulting cross-linked micelles with disulfide bonds represented soft, hydrogel-like nanospheres and demonstrated a time-dependent degradation in the conditions mimicking the intracellular reducing environment. The ionic character of the cores allowed to achieve a very high level of doxorubicin (DOX) loading (50% w/w) into the cross-linked micelles. DOX-loaded degradable cross linked micelles exhibited more potent cytotoxicity against human A2780 ovarian carcinoma cells as compared to micellar formulations without disulfide linkages. These novel biodegradable cross-linked micelles are expected to be attractive candidates for delivery of anticancer drugs. PMID- 20307097 TI - Covalently attached, silver-doped poly(vinyl alcohol) hydrogel films on poly(l lactic acid). AB - Covalently attached, soft poly(vinyl alcohol) (PVA) hydrogel films containing silver particles were prepared on solid biodegradable poly(l-lactic acid) (PLLA) samples by a multistep procedure involving oxygen plasma treatment, UV-initiated graft polymerization, and chemical grafting methods. The modification steps were followed and verified using attenuated total reflection infrared spectroscopy and X-ray photoelectron spectroscopy. 2-Hydroxyethyl methacrylate (HEMA) was graft polymerized from the surface of oxygen plasma-treated PLLA film samples and the alcohol functionality in the grafted polyHEMA chains was oxidized using pyridinium dichromate to obtain an aldehyde-rich surface. PVA was then grafted onto this surface using acid catalysis (acetal formation). The "freeze/thaw method" was used to form a PVA hydrogel layer that incorporated the covalently grafted PVA chains in the physically cross-linked gel. This composite film (PLLA PVA(gel)) was doped with silver ions, which were reduced to silver using NaBH(4). Scanning electron microscopy of cross sections of PLLA-PVA(gel) indicates robust attachment of the PVA hydrogel layer to the PLLA film. PLLA-PVA(gel/Ag(0)) film samples exhibit both antibacterial and reduced cell adhesion properties due to the antibacterial properties of silver nanoparticles and high water content, respectively. This method provides a route to mechanically sound biodegradable materials with tunable soft material surface properties. Potential applications in tissue engineering and biomedical devices are envisioned. PMID- 20307098 TI - Proteome and flavonoid analysis reveals distinct responses of epidermal tissue and whole leaves upon UV-B radiation of barley (Hordeum vulgare L.) seedlings. AB - We describe here the effect of UV-B irradiation on the proteome and flavonoid content of the barley seedling leaf epidermis and mesophyll. Flavonoid analysis was performed using UPLC-PDA/-MS. The major flavonoid molecule responding to UV-B radiation was saponarin, and this accumulated in the epidermis, but not in the mesophyll. Changes in protein expression were determined using two-dimensional gel electrophoresis (2-DE) and identified 11 responsive proteins (seven up regulated and two down-regulated in the epidermis; and one up- and one down regulated in the mesophyll). A label-free LC-MS/MS(E) approach was applied for a subset of samples consisting of epidermis tissue and was able to detect a further 15 (11 up-regulated and four down-regulated) proteins. Most of the proteins with changed expression pattern after UV-B treatment were involved in initial responses characteristic for oxidative stress. Others were primary metabolism proteins involved in the supply of precursors for secondary metabolites. A separate analysis of epidermis and mesophyll tissue is important to give a spatially resolved picture of the response to UV-B treatment. The label-free LC MS/MS(E) approach is complementary to the more conventional two-dimensional gel electrophoresis, as there was no overlap between the spectra of proteins identified by the two techniques. PMID- 20307099 TI - Solid-state (17)O NMR and computational studies of C-nitrosoarene compounds. AB - We report the first solid-state (17)O NMR determination of the (17)O quadrupole coupling (QC) tensor and chemical shift (CS) tensor for four (17)O-labeled C nitrosoarene compounds: p-[(17)O]nitroso-N,N-dimethylaniline ([(17)O]NODMA), SnCl(2)(CH(3))(2)([(17)O]NODMA)(2), ZnCl(2)([(17)O]NODMA)(2), and [(17)O]NODMA.HCl. The (17)O quadrupole coupling constants (C(Q)) observed in these C-nitrosoarene compounds are on the order of 10-15 MHz, among the largest values found to date for organic compounds. The (17)O CS tensor in these compounds exhibits remarkable sensitivity toward the nitroso bonding scheme with the chemical shift anisotropy (delta(11) - delta(33)) ranging from just 350 ppm in [(17)O]NODMA.HCl to over 2800 ppm in [(17)O]NODMA. This latter value is among the largest (17)O chemical shift anisotropies reported in the literature. These extremely anisotropic (17)O NMR interactions make C-nitrosoarene compounds excellent test cases that allow us to assess the detection limit of solid-state (17)O NMR. Our results suggest that, at 21.14 T, solid-state (17)O NMR should be applicable to all oxygen-containing organic functional groups. We also show that density functional theory (DFT) calculations can reproduce reasonably well the experimental (17)O QC and CS tensors for these challenging molecules. By combining quantum chemical calculations with experimental solid-state (17)O NMR results, we are able to determine the (17)O QC and CS tensor orientations in the molecular frame of reference for C-nitrosoarenes. We present a detailed analysis illustrating how magnetic field-induced mixing between individual molecular orbitals (MOs) contributes to the (17)O shielding tensor in C-nitrosoarene compounds. We also perform a Townes-Dailey analysis for the observed (17)O QC tensors and show that (17)O CS and QC tensors are intrinsically related through the pi bond order of the N horizontal lineO bond. Furthermore, we are able for the first time to examine the parallelism between individual (17)O and (15)N CS tensor components in C-nitrosoarenes. PMID- 20307100 TI - Encapsulation of a radiolabeled cluster inside a fullerene cage, (177)Lu(x)Lu((3 x))N@C(80): an interleukin-13-conjugated radiolabeled metallofullerene platform. AB - In this communication, we describe the successful encapsulation of (177)Lu into the endohedral metallofullerene (177)Lu(x)Lu(3-x)N@C(80) (x = 1-3) starting with (177)LuCl(3) in a modified quartz Kraschmer-Huffman electric generator. We demonstrate that the (177)Lu (beta-emitter) in this fullerene cage is not significantly released for a period of up to at least one-half-life (6.7 days). We also demonstrate that this agent can be conjugated with an interleukin-13 peptide that is designed to target an overexpressed receptor in glioblastoma multiforme tumors. This nanoparticle delivery platform provides flexibility for a wide range of radiotherapeutic and radiodiagnostic multimodal applications. PMID- 20307103 TI - Sustainability through nanotechnology. PMID- 20307102 TI - Thermodynamic changes in mechanochemically synthesized magnesium hydride nanoparticles. AB - The thermodynamic properties of magnesium hydride nanoparticles have been investigated by hydrogen decomposition pressure measurements using the Sieverts technique. A mechanochemical method was used to synthesize MgH(2) nanoparticles (down to approximately 7 nm in size) embedded in a LiCl salt matrix. In comparison to bulk MgH(2), the mechanochemically produced MgH(2) with the smallest particle size showed a small but measurable decrease in the decomposition reaction enthalpy (DeltaH decrease of 2.84 kJ/mol H(2) from DeltaH(bulk) = 74.06 +/- 0.42 kJ/mol H(2) to DeltaH(nano) = 71.22 +/- 0.49 kJ/mol H(2)). The reduction in DeltaH matches theoretical predictions and was also coupled with a similar reduction in reaction entropy (DeltaS decrease of 3.8 J/mol H(2)/K from DeltaS(bulk) = 133.4 +/- 0.7 J/mol H(2)/K to DeltaS(nano) = 129.6 +/- 0.8 J/mol H(2)/K). The thermodynamic changes in the MgH(2) nanoparticle system correspond to a drop in the 1 bar hydrogen equilibrium temperature (T(1 bar)) by approximately 6 degrees C to 276.2 +/- 2.4 degrees C in contrast to the bulk MgH(2) system at 281.8 +/- 2.2 degrees C. The reduction in the desorption temperature is less than that expected from theoretical studies due to the decrease in DeltaS that acts to partially counteract the effect from the change in DeltaH. PMID- 20307105 TI - Forster resonance energy transfer in dye-sensitized solar cells. AB - It appears that the efficiency of dye-sensitized solar cells (DSSCs) has reached a ceiling due to the limited absorption spectrum of currently available dyes. To achieve new record efficiencies, light absorption must be extended into the near infrared region of the spectrum without sacrificing performance in the visible region. No single dye has this ability, but there is greater strength in numbers. Forster resonance energy transfer (FRET) may be used to link two or more materials to provide strong absorption across a broad portion of the solar spectrum. This process has been shown to be effective and efficient, and a recent breakthrough in FRET-enhanced DSSCs is presented in this issue. This Perspective explores the background of this topic and considers directions for future development. PMID- 20307107 TI - Development and validation of the College Life Alcohol Salience Scale: a measure of beliefs about the role of alcohol in college life. AB - This article reports the development and validation of the College Life Alcohol Salience Scale (CLASS), which assesses college students' beliefs about the centrality of alcohol to the college experience. Developed using procedures designed to increase its ecological validity, the CLASS was administered to three samples of college students (total N = 571). Its unidimensional factor structure was first established via exploratory factor analysis and parallel analysis on one sample and then verified via confirmatory factor analysis on a separate sample. Scores on the CLASS were predictably related to a nomological network of drinking and personality variables and it provided incremental validity in accounting for drinking frequency and amount, when added to drinking motive scores. The importance of assessing and developing interventions to target the types of beliefs measured by the CLASS is discussed. PMID- 20307106 TI - Activation of aortic endothelial cells by oxidized phospholipids: a phosphoproteomic analysis. AB - Previous studies have shown that oxidized products of the phospholipid PAPC (Ox PAPC) are strong activators of aortic endothelial cells and play an important role in atherosclerosis and other inflammatory diseases. We and others have demonstrated that Ox-PAPC activates specific signaling pathways and regulates a large number of genes. Using a phosphoproteomic approach based on phosphopeptide enrichment and mass spectrometry analysis, we identified candidate changes in Ox PAPC-induced protein phosphorylation of 228 proteins. Functional annotation of these proteins showed an enrichment of the regulation of cytoskeleton, junctional components, and tyrosine kinases, all of which may contribute to the phenotypic and molecular changes observed in endothelial cells treated with Ox-PAPC. Many changes in protein phosphorylation induced by Ox-PAPC are reported here for the first time and provide new insights into the mechanism of activation by oxidized lipids, including phosphorylation-based signal transduction. PMID- 20307108 TI - Explicit and implicit measures of expectancy and related alcohol cognitions: a meta-analytic comparison. AB - Implicit measures assess the influence of past experience on present behavior in the absence of respondents' awareness of that influence. Application of implicit measurement to expectancy and related alcohol cognition research has helped elucidate the links between alcohol-related experiences, the functioning of alcohol-related memory, and alcohol-related behavior. Despite these advances, a coherent picture of the role of implicit measurement has been difficult to achieve because of the diversity of implicit measures used. Two central questions have emerged: Do implicit measures assess a distinct aspect of the alcohol associative memory domain not accessible via explicit measurement; when compared with explicit measurement, do they offer unique prediction of alcohol consumption? To address these questions, the authors conducted a meta-analysis of studies using both implicit and explicit measures of alcohol expectancy and other types of alcohol-related cognition. Results indicate that implicit and explicit measures are weakly related, and although they predict some shared variance in drinking, each also contributes a unique component. Results are discussed in the context of the theoretical distinction made between the 2 types of measures. PMID- 20307110 TI - What is the latent structure of alcohol use disorders? A taxometric analysis of the Personality Assessment Inventory Alcohol Problems Scale in male and female prison inmates. AB - Three indicators derived from the Personality Assessment Inventory (PAI) Alcohol Problems scale (ALC)-tolerance/high consumption, loss of control, and negative social and psychological consequences-were subjected to taxometric analysis-mean above minus below a cut (MAMBAC), maximum covariance (MAXCOV), and latent mode factor analysis (L-Mode)-in 1,374 federal prison inmates (905 males, 469 females). Whereas the total sample yielded ambiguous results, the male subsample produced dimensional results, and the female subsample produced taxonic results. Interpreting these findings in light of previous taxometric research on alcohol abuse and dependence it is speculated that while alcohol use disorders may be taxonic in female offenders, they are probably both taxonic and dimensional in male offenders. Two models of male alcohol use disorder in males are considered, one in which the diagnostic features are categorical and the severity of symptomatology is dimensional, and one in which some diagnostic features (e.g., withdrawal) are taxonic and other features (e.g., social problems) are dimensional. PMID- 20307111 TI - A longitudinal analysis of drinking motives moderating the negative affect drinking association among college students. AB - We examined among college students (N = 530; 276 women) the moderating effects of avoidance (coping) and appetitive (social-enhancement) drinking motives on the within-person associations between anxious and depressive affect and drinking frequency and quantity. Once per year for up to 4 years participants completed standard measures of drinking motives and retrospective reports of affect and drinking in the previous month. In addition, each year they completed a 30-day daily diary of affect and drinking. Results from models examining both the retrospective and aggregate daily data indicated that individuals with high compared with low social-enhancement motives showed stronger positive associations among changes in monthly negative affect and drinking frequency. Weak evidence was found for the predicted moderating effects of coping motives, although some results indicated that its effects were contingent on levels of social-enhancement motives. Our findings suggest that appetitive drinking motives might play an integral role in stress- and negative-affect related drinking among college students. PMID- 20307113 TI - Nicotine dependence subtypes among adolescent smokers: examining the occurrence, development and validity of distinct symptom profiles. AB - To increase understanding of the etiology and epidemiology of nicotine dependence among adolescent smokers, the present study examined the occurrence and development of distinct nicotine dependence symptom profiles in a sample of adolescent smokers. A total of 25 secondary schools throughout the Netherlands participated in a 1-year longitudinal study. Multiple dimensions of nicotine dependence were assessed, at two time points, among 641 adolescents (aged 14-17 years) who were classified as smokers. Results showed 4 distinct, yet stable, nicotine dependence subtypes that could be characterized by quantitative as well as qualitative differences. The symptom profiles were similar for males and females but differentially associated with previously identified correlates of nicotine dependence, namely parental smoking, peer smoking, and depressive mood. Finally, differential links of the 4 subtypes were found with regard to smoking uptake and cessation. The finding of qualitative different subgroups of adolescent smokers may have important implications for intervention efforts regarding nicotine dependence and smoking cessation. Such efforts may need to be tailored to the specific subgroups' needs. PMID- 20307112 TI - Does adolescent alcohol and marijuana use predict suppressed growth in psychosocial maturity among male juvenile offenders? AB - Multiple theories suggest mechanisms by which the use of alcohol and drugs during adolescence could dampen growth in psychosocial maturity. However, scant empirical evidence exists to support this proposition. The current study tested whether alcohol and marijuana use predicted suppressed growth in psychosocial maturity among a sample of male serious juvenile offenders (n = 1,170) who were followed from ages 15 to 21 years. Alcohol and marijuana use prospectively predicted lower maturity 6 months later. Moreover, boys with the greatest increases in marijuana use showed the smallest increases in psychosocial maturity. Finally, heterogeneity in the form of age-related alcohol and marijuana trajectories was related to growth in maturity, such that only boys who decreased their alcohol and marijuana use significantly increased in psychosocial maturity. Taken together, these findings suggest that patterns of elevated alcohol and marijuana use in adolescence may suppress age-typical growth in psychosocial maturity from adolescence to young adulthood, but that effects are not necessarily permanent, because decreasing use is associated with increases in maturity. PMID- 20307114 TI - Outcome expectancies and gambling behavior among urban adolescents. AB - This project sought to identify adolescent outcome expectancies for gambling and to evaluate their relation to gambling behavior among a sample of urban adolescents. In a preliminary study, 50 outcome expectancies were identified on the basis of a literature review or generated after surveying 35 urban high school students. These expectancies were then administered to 1,076 urban high school students. Rates of at-risk and problem gambling were 14.6% and 12.7%, respectively. Exploratory and confirmatory factor analyses were performed on randomly selected halves of the sample and identified 5 expectancy domains. In a structural equation model, material gain, negative affect, and positive self evaluation displayed significant positive relations, and negative social consequences and parent disapproval displayed significant negative relations, to gambling behavior. The model explained 48% of the variance in gambling problems and 58% of the variance in gambling frequency. These results demonstrate the salience of gambling-related cognitions in understanding the gambling behavior among these at-risk youth and suggest that expectancies may be important prevention targets for this population. PMID- 20307115 TI - Using the theory of planned behavior to predict gambling behavior. AB - Gambling is an important public health concern. To better understand gambling behavior, we conducted a classroom-based survey that assessed the role of the theory of planned behavior (TPB; i.e., intentions, subjective norms, perceived behavioral control, and attitudes) in past-year gambling and gambling frequency among college students. Results from this research support the utility of the TPB to explain gambling behavior in this population. Specifically, in TPB models to predict gambling behavior, friend and family subjective norms and perceived behavioral control predicted past-year gambling, and friend and family subjective norms, attitudes, and perceived behavioral control predicted gambling frequency. Intention to gamble mediated these relationships. These findings suggest that college-based responsible gambling efforts should consider targeting misperceptions of approval regarding gambling behavior (i.e., subjective norms), personal approval of gambling behavior (i.e., attitudes), and perceived behavioral control to better manage gambling behavior in various situations. (PsycINFO Database Record (c) 2010 APA, all rights reserved). PMID- 20307116 TI - Associations between family structure, family functioning, and substance use among Hispanic/Latino adolescents. AB - This study examined the role of family structure and functioning in predicting substance use among Hispanic/Latino adolescents, surveyed in 9th and 10th grade. The sample (N = 1433) was half female, mostly of Mexican descent, and the majority was born in the United States. Living with a single father was associated with less parental monitoring and less family cohesion (gamma = -0.07, -0.06, respectively). Living with a single mother was associated with less parental monitoring (gamma = -0.10). Living with neither parent was associated with less communication (gamma = -0.08), less parental monitoring (gamma = 0.09), more family conflict (gamma = 0.06), and less family cohesion (gamma = 0.06). Less monitoring was associated with substance use at follow-up (beta = 0.17). Low rates of parental monitoring appear to mediate the association between parental family structure and substance use. Results suggest that improving basic parenting skills and offering additional social support and resources to assist parents in monitoring adolescents may help prevent substance use. These interventions may be particularly beneficial for single parents. PMID- 20307119 TI - Self-injury, substance use, and associated risk factors in a multi-campus probability sample of college students. AB - This research examined two questions: (1) What is the prevalence of self injurious behavior (SIB) among college students, overall and by gender, academic level, and sexual orientation? (2) To what extent is SIB associated with different forms of substance use and other risk behaviors? A probability sample of 5,689 students completed an Internet survey on self-injury, mental health, and substance use. Past-year prevalence of SIB was 14.3%, with undergraduates significantly more likely than graduate students to engage in SIB. Drug use and frequent binge drinking were associated with higher rates of SIB. Among those who engaged in any SIB, those who used drugs had higher depression scores, higher prevalence of cigarette smoking, and higher rates of binge eating. In a multiple logistic regression model predicting SIB, depression, cigarette smoking, gambling, and drug use were significant predictors. Information about those at risk for SIB is critical for the design of prevention and intervention efforts as colleges continue to grapple with risky behaviors. PMID- 20307117 TI - Relationships over time between mental health symptoms and transmission risk among persons living with HIV. AB - Relationships between mental health symptoms (anxiety and depression) or a positive state of mind and behavior associated with HIV transmission (substance use and risky sexual behavior) were explored in a longitudinal study of persons living with HIV (PLH; N = 936) who were participants in a transmission-prevention trial. Bivariate longitudinal regressions were used to estimate the correlations between mental health symptoms and HIV-related transmission acts for 3 time frames: at the baseline interview, over 25 months, and from assessment to assessment. At baseline, mental health symptoms were associated with transmission acts. Elevated levels of mental health symptoms at baseline were associated with decreasing alcohol or marijuana use over 25 months. Over 25 months, an increasingly positive state of mind was associated with decreasing alcohol or marijuana use; an increasingly positive state of mind in the immediate intervention condition and increasing depressive symptoms in the lagged condition were related to increasing risky sexual behavior. Our findings suggest that mental health symptoms precede a decrease in substance use and challenge self medication theories. Changes in mental health symptoms and sexual behavior occur more in tandem. PMID- 20307120 TI - Mood and personality-based models of substance use. AB - Mood and personality-based vulnerabilities have been extensively examined in patients with substance use disorders, but their relevance as models of etiology remains to be fully investigated. The present investigation examined mood and personality-based models of substance use in a nonclinical sample of young adults. Two-hundred and twelve individuals were assessed for personality and clinical characteristics and participated in computerized ambulatory monitoring of mood states and substance use over a 1-week period. Personality factors were strong predictors of substance use frequency over the previous 30 days, as well as of substance use in daily life using ambulatory monitoring. A linear increase was also observed in the intensity of novelty seeking and antisocial personality traits as a function of the social deviance of substances used. However, mood disorder history was related only to the use of illicit drugs other than cannabis, and fluctuations in mood states did not prospectively predict daily use of substances in a manner consistent with self-medication. Moreover, there was little evidence that personality characteristics moderated relations between mood states and substance use in daily life. The relevance of results for mood and personality models of substance use etiology is discussed. PMID- 20307121 TI - Validation of a contemplation ladder in an adult substance use disorder sample. AB - Developing brief measures of motivation to abstain from substance use that reliably predict treatment retention and outcome is a high priority in the addiction field. This study examined the psychometric properties of a contemplation ladder designed to assess readiness to abstain from alcohol and drug use respectively, on the basis of the contemplation ladder for smoking cessation developed by Biener and Abrams (1991). Participants were 394 substance using male and female welfare recipients referred for treatment. The combined alcohol and other drug (AOD) ladder showed discriminant validity with demographic and health characteristics, convergent validity with conceptually related treatment motivation variables, concurrent validity with baseline AOD treatment and substance use variables, and predictive validity for participation in treatment services up to 1 month later and abstinence outcomes up to 1 year later. The AOD ladder showed predictive validity for those in drug-free treatment and no treatment at baseline but not for those in methadone maintenance. PMID- 20307122 TI - Action identification of drinking and self-control. AB - A number of investigators have proposed that self-control over addictive behaviors may be influenced by the way individuals mentally represent their actions. Previous research based on questionnaires has suggested that those who report higher-level identifications of their alcohol use behavior may exhibit more difficulty controlling their alcohol use (Wegner, Vallacher, & Dizadji, 1989). However, it is unclear whether this association is because of characteristic ways of mentally representing specific drinking events or the fact that those who have more impaired control consume more alcohol and drink across a broader array of situations. The current study sought to address this question by examining the association between impaired control over alcohol and action identification of drinking behavior in a structured laboratory drinking task. Ninety-one young adult hazardous drinkers (21-35 years) completed the Impaired Control Over Alcohol Scale (Heather, Tebbut, Mattick, & Zamir, 1993) and an alcohol consumption task. Participants then completed a Likert scale measure to assess action identification of their drinking behavior. Results showed that those who reported greater impaired control over alcohol experienced the drinking task at higher-level action identification even when accounting for alcohol consumption variables. These findings are consistent with the view that higher level identification of alcohol use behavior may hinder self-control (Wegner et al., 1989), and that self-management approaches may be enhanced through strategies to address mental representation of action. PMID- 20307123 TI - Distractibility moderates the relation between automatic alcohol motivation and drinking behavior. AB - Research suggests that alcohol use is influenced by (a) the strength of automatic motivational responses to alcohol cues and (b) individual differences in self control. The current study was designed to examine whether the self-control skill of inhibiting response to distracting stimuli would moderate the relation between automatic alcohol motivation and alcohol use. Eighty-seven hazardous drinkers completed baseline measures of automatic alcohol motivation and trait self control and reported their drinking at a follow-up session 6 weeks later. Regression analyses demonstrated an interaction such that greater distractibility strengthens a positive relation between alcohol use and automatic alcohol motivation. These results contribute to a growing body of work indicating that self-control resources may help to inhibit the influence of automatic processes on alcohol behavior. PMID- 20307124 TI - Testing the incentive-sensitization theory with at-risk drinkers: wanting, liking, and alcohol consumption. AB - Motivational models of addiction typically propose that alcohol and drugs are desired because of their hedonic effects (i.e., increasing pleasure or reducing distress). In contrast, the incentive-sensitization theory proposes that wanting motivation and liking motivation are separable and that after repeated substance use, motivation shifts from liking to wanting. Using a sample of 85 at-risk drinkers (as defined by the National Institute on Alcohol Abuse and Alcoholism), in the current study we examined the separability of liking motivation and wanting motivation for alcohol and whether years of drinking experience was associated with an increased role for wanting motivation and a decreased role for liking motivation. Consumption was measured with a free-drinking task. Wanting motivation was assessed immediately before drinking, and liking was assessed immediately after drinking had begun. The results indicated that (a) wanting motivation predicted variance of consumption unique from that accounted for by liking motivation, (b) longer drinking experience was associated with a decreased relation between liking motivation and consumption, and (c) longer drinking experience was not associated with an increased relation between wanting motivation and consumption. The results provide partial support for the incentive sensitization theory. PMID- 20307125 TI - Frequency and correlates of diary-measured hangoverlike experiences in a college sample. AB - A sample of college students, oversampled for smoking (N = 127, 43% smokers), monitored their daily experiences using electronic diaries over 14 days. We examined the frequency and correlates of liberally defined hangoverlike experiences (HLEs) using data from 1,595 person-days (1,325 after abstention from drinking and 270 after drinking, including 125 HLEs). More than 40% of the sample reported at least one HLE, and nearly half of all drinking episodes were followed by HLE. Endorsement of HLE was more likely as the number of drinks increased and was associated with modest elevations of hangover symptoms. Gender did not predict rates of overall HLE endorsement, but male students were less likely than female students to report an HLE after a drinking episode and showed a weaker relation between number of drinks and HLE. Smokers were more likely to report HLE, but there was no evidence that smoking status was associated with increased HLE susceptibility. Self-reported parental alcohol problems were associated with more frequent HLE and incrementally predicted HLE endorsement when number of drinks was covaried. The findings suggest that HLE is a common outcome of college drinking and attest to the feasibility of using electronic diaries to assess its episode- and person-level correlates. PMID- 20307126 TI - A brief image-based prevention intervention for adolescents. AB - The authors evaluated the efficacy of a brief image-based prevention intervention and assessed current drug use as a moderator of intervention effects. In a clinical trial, 416 high school-age adolescents were randomized to either the brief intervention or usual care control, with data collected at baseline and 3 month follow-up. The brief intervention consisted of a tailored in-person communication and a series of parent/guardian print materials based on the behavior-image model. Health behavior goal setting increased for participants receiving the brief intervention, with an effect size in the small range (d = 0.33). Overall effect sizes for cigarette smoking frequency and quantity and alcohol use frequency and quantity were small (ds = 0.16-0.21) and in favor of the brief intervention. However, adolescents reporting current substance use who received the brief intervention reduced their frequency and heavy use of alcohol, frequency and quantity of cigarette smoking, and reported fewer alcohol/drug problems, with larger effects ranging from small to approaching medium in size (ds = 0.32-0.43, ps < .01). This study suggests that brief image-based messages may increase health behavior goal setting and reduce substance use, particularly among drug-using older adolescents. PMID- 20307127 TI - Shifting closeness: interpersonal effects of personal goal progress. AB - In this article, we examine how the shifting motivational priority of personal goals affects relationship closeness. We hypothesize that people will draw closer to significant others who are instrumental (vs. noninstrumental) for a goal that has not been progressing well-a goal that is thus high in motivational priority. Once the goal has progressed successfully, we predict that people will cease to draw closer to instrumental others. Five studies support these predictions by showing that the impact of goal progress on reduced preference for instrumental others (Experiment 1) depends on the framing of progress as partial attainment (vs. greater commitment, Experiment 2) and the intention to balance across goals (vs. focus on one goal; Experiments 3-4). We find that moving away from instrumental others post progress is functional, in that it allows for drawing closer to those who are instrumental for alternative goals (Experiment 5). PMID- 20307128 TI - Yes, but what's the mechanism? (don't expect an easy answer). AB - Psychologists increasingly recommend experimental analysis of mediation. This is a step in the right direction because mediation analyses based on nonexperimental data are likely to be biased and because experiments, in principle, provide a sound basis for causal inference. But even experiments cannot overcome certain threats to inference that arise chiefly or exclusively in the context of mediation analysis-threats that have received little attention in psychology. The authors describe 3 of these threats and suggest ways to improve the exposition and design of mediation tests. Their conclusion is that inference about mediators is far more difficult than previous research suggests and is best tackled by an experimental research program that is specifically designed to address the challenges of mediation analysis. PMID- 20307129 TI - Increasing or decreasing interest in activities: the role of regulatory fit. AB - What makes people's interest in doing an activity increase or decrease? Regulatory fit theory (E. T. Higgins, 2000) provides a new perspective on this classic issue by emphasizing the relation between people's activity orientation, such as thinking of an activity as fun, and the manner of activity engagement that the surrounding situation supports. These situational factors include whether a reward for good performance, expected (Study 1) or unexpected (Study 2), is experienced as enjoyable or as serious and whether the free-choice period that measures interest in the activity is experienced as enjoyable or as serious (Study 3). Studies 1-3 found that participants were more likely to do a fun activity again when these situational factors supported a manner of doing the activity that fit the fun orientation-a reward or free-choice period framed as enjoyable. This effect was not because interest in doing an activity again is simply greater in an enjoyable than a serious surrounding situation because it did not occur, and even reversed, when the activity orientation was important rather than fun, where now a serious manner of engagement provides the fit (Study 4a and 4b). PMID- 20307130 TI - Nostalgia as a repository of social connectedness: the role of attachment-related avoidance. AB - Individuals who are low (compared with high) in attachment-related avoidance rely on social bonds to regulate distress, and the authors hypothesized that nostalgia can be a repository of such social connectedness. Studies 1-3 showed a positive association between loneliness and nostalgia when attachment-related avoidance was low, but not when it was high. Study 4 revealed that low-avoidance individuals derived more social connectedness from nostalgia than did high avoidance individuals. Study 5 extended these findings and demonstrated that, in addition to being a source of social connectedness, nostalgia increased participants' perceived capacity to provide emotional support to others. As in the case of social connectedness, this beneficial effect of nostalgia was significantly stronger when attachment-related avoidance was low (compared with high). PMID- 20307131 TI - When "negative" behaviors are positive: a contextual analysis of the long-term effects of problem-solving behaviors on changes in relationship satisfaction. AB - How should partners discuss the problems that arise over the course of their intimate relationships? Prior studies have provided inconsistent answers to this question, with some suggesting that partners benefit by avoiding negative behaviors and others suggesting that partners benefit by engaging in negative behaviors. The 2 longitudinal studies of newlyweds described here reconcile these inconsistent findings by revealing that direct negative problem-solving behaviors interact with the severity of the problems couples face in their relationships to account for changes in relationship satisfaction. Whereas spouses' tendencies to blame, command, and reject their partners predicted steeper declines in their own marital satisfaction when exhibited in the context of relationships facing only minor problems, those same behaviors predicted more stable satisfaction in relationships facing more severe problems. Subsequent analyses revealed that changes in the severity of the problems themselves mediated these effects. By contrast, indirect negative communications were associated with stably lower levels of satisfaction regardless of problem severity. The current findings join others in highlighting the theoretical importance of accounting for the relational context when examining the implications of various interpersonal processes. PMID- 20307132 TI - The schema-driven chameleon: how mimicry affects executive and self-regulatory resources. AB - The authors propose that behavioral mimicry is guided by schemas that enable efficient social coordination. If mimicry is schema driven, then the operation of these schemas should be disrupted if partners behave in counternormative ways, such as mimicking people they generally would not or vice versa, rendering social interaction inefficient and demanding more executive and self-regulatory resources. To test this hypothesis, Experiments 1-3 used a resource-depletion paradigm in which participants performed a resource-demanding task after interacting with a confederate who mimicked them or did not mimic them. Experiment 1 demonstrated impaired task performance among participants who were not mimicked by a peer. Experiments 2 and 3 replicated this effect and also demonstrated a significant reversal in social contexts where mimicry is counternormative, suggesting that inefficiency emerges from schema inconsistency, not from the absence of mimicry per se. Experiment 4 used a divided attention paradigm and found that resources are taxed throughout schema-inconsistent interactions. These findings suggest that much-needed resources are preserved when the amount of mimicry displayed by interacting individuals adheres to norms, whereas resources are depleted when mimicry norms are violated. PMID- 20307133 TI - Compassion, pride, and social intuitions of self-other similarity. AB - Compassion and pride serve contrasting social functions: Compassion motivates care-taking behavior, whereas pride enables the signaling and negotiation of rank within social hierarchies. Across 3 studies, compassion was associated with increased perceived self-other similarity, particularly to weak or vulnerable others. In contrast, pride was associated with an enhanced sense of similarity to strong others, and a decreased sense of similarity to weak others. These findings were obtained using trait measures (Study 1) and experimental inductions (Studies 2 and 3) of compassion and pride, examining the sense of similarity to strong or weak groups (Studies 1 and 2) and unfamiliar individuals (Study 3). The influences of compassion and pride on perceived self-other similarity could not be accounted for by positive mood, nor was this effect constrained by the ingroup status of the target group or individual. Discussion focuses on the contributions these findings make to an understanding of compassion and pride. PMID- 20307134 TI - Social support, problem solving, and the longitudinal course of newlywed marriage. AB - Married couples (N = 172) were observed as newlyweds and observed again 1 year later while engaging in 2 problem-solving and 2 personal support discussions. Microanalytic coding of these conversations was used to examine associations between problem-solving and social support behaviors for 1 year and their relative contributions to 10-year trajectories of self-reported relationship satisfaction and dissolution. Results demonstrated that initially lower levels of positive support behaviors and higher levels of negative support behaviors predicted 1-year increases in negative emotion displayed during problem-solving conversations. Emotions coded from the initial problem-solving conversations did not predict 1-year changes in social support behaviors. Controlling for emotions displayed during problem-solving interactions eliminated or reduced associations between initial social support behaviors and (a) later levels of satisfaction and (b) relationship dissolution. These findings corroborate models that prioritize empathy, validation, and caring as key elements in the development of intimacy (e.g., Reis & Shaver, 1988) and suggest that deficits in these domains foreshadow deterioration in problem solving and conflict management. Implications for integrating support and problem solving in models of relationship change are outlined, as are implications for incorporating social support in education programs for developing relationships. PMID- 20307135 TI - Self-esteem development from young adulthood to old age: a cohort-sequential longitudinal study. AB - The authors examined the development of self-esteem from young adulthood to old age. Data came from the Americans' Changing Lives study, which includes 4 assessments across a 16-year period of a nationally representative sample of 3,617 individuals aged 25 years to 104 years. Latent growth curve analyses indicated that self-esteem follows a quadratic trajectory across the adult life span, increasing during young and middle adulthood, reaching a peak at about age 60 years, and then declining in old age. No cohort differences in the self-esteem trajectory were found. Women had lower self-esteem than did men in young adulthood, but their trajectories converged in old age. Whites and Blacks had similar trajectories in young and middle adulthood, but the self-esteem of Blacks declined more sharply in old age than did the self-esteem of Whites. More educated individuals had higher self-esteem than did less educated individuals, but their trajectories were similar. Moreover, the results suggested that changes in socioeconomic status and physical health account for the decline in self esteem that occurs in old age. PMID- 20307136 TI - A meta-analysis of normal and disordered personality across the life span. AB - Debate continues about whether personality, both normal and disordered, can change significantly or is mainly stable across the life span. One issue that receives little attention is the degree to which personality stability coefficients may be influenced by attenuation due to measurement error. The current meta-analysis examines the data from recent research on personality stability, reporting both uncorrected and corrected stability coefficients. Attenuation due to measurement error was found to cause a significant reduction in personality stability coefficients, raising the possibility that some studies may conflate personality change with measurement error. Overall, corrected stability coefficients suggested that the stability of personality across adulthood is high, with only modest change. By contrast, personality during childhood is significantly more changeable. Both normal personality and personality disorders were highly stable across the life span, and patients in therapy experienced no more personality change than did nonpatients. Cross cultural comparisons suggested relatively similar levels of personality stability cross-culturally, although personality stability among people in South Pacific nations is slightly lower than among those in the United States, Canada, or European nations. PMID- 20307137 TI - The letter of recommendation effect in informant ratings of personality. AB - In most studies using informant reports of personality, the informants are recruited by the targets. Such informants may tend to like the targets and thus portray them in specific ways (e.g., too positively). Study 1 (N = 403) demonstrated the necessity to distinguish between "liking" and "knowing" in studying the relationships between informants and targets. Informants who liked their targets better described them more positively (i.e., as being more extraverted, agreeable, open, conscientious, and less neurotic). The association between personality ratings and liking was moderated by item evaluativeness. Liked targets were also described as being more similar to each other (range restriction), which would lower correlations of informant ratings of personality with external variables. Study 2 (N = 90) used a within-subjects design to disentangle actual personality differences between targets (substance) from the informants' specific views on the targets (style). Ninety informants were asked to nominate targets they did not like. These targets then nominated informants of their own choice. Target-nominated informants liked the targets very much and described the targets' personalities very positively and in ways that were highly redundant with the average target's self-rating. There was evidence that lower liking may be associated with better accuracy. Higher subjective levels of knowing were not associated with better interrater agreement but with a greater willingness to describe targets negatively. Implications for the field of recruiting are discussed. Where possible, the choice of informants and referees should be made independent of the targets' preferences. PMID- 20307138 TI - Hepatic CYP2B6 is altered by genetic, physiologic, and environmental factors but plays little role in nicotine metabolism. AB - Human cytochrome P4502B6 (CYP2B6) is predominantly expressed in the liver and it plays a major role in the metabolism of several therapeutically important drugs and environmental toxicants. The objective was twofold: (1) to determine the role of genetic, physiological, and environmental factors in predicting hepatic CYP2B6 protein expression; and (2) to investigate the role of CYP2B6 in nicotine C oxidation. Human livers (n = 40) were assessed for CYP2B6 protein and genotype. Linear regression analyses indicated that CYP2B6 genotype (10%), gender (14%), and exposure to inducers (21%), but not age, were predictors of CYP2B6 protein amounts. Livers with at least one CYP2B6*5 or *6 allele were associated with lower CYP2B6. Female livers and livers exposed to inducers (phenobarbital and/or dexamethasone) were associated with higher CYP2B6. A weak correlation between CYP2B6 and nicotine C-oxidation activity was observed, which was abrogated when controlling for CYP2A6 protein levels. CYP2B6*6 was not associated with different nicotine kinetics. In summary, CYP2B6 protein expression was associated with genotype, gender, and exposure to inducers, but not with nicotine C-oxidation activity. PMID- 20307139 TI - Evaluation of indomethacin and dexamethasone effects on BCRP-mediated drug resistance in MCF-7 parental and resistant cell lines. AB - Breast cancer resistance protein is a member of the ATP-binding cassette transporter G family that extrudes xenotoxins from cells, mediating drug resistance, and has been recognized as a major cause of failure of various carcinoma chemotherapies. In this study, the modulatory effects of dexamethasone and indomethacin on the cell cytotoxicity of mitoxantrone and on the BCRP protein activity in breast cancer cell lines were examined. MCF cells were seeded at 1 x 10(4) cells per well in 96-well flat-bottomed microplates for 48 hours and treated with increasing doses of dexamethasone, indomethacin, and novobiocin alone or preincubated with increasing doses of the drugs and then coexposed to mitoxantrone. Cell viability was measured after 1-4 days, using the MTT assay. BCRP activity was determined flow cytometrically by measuring mitoxantrone accumulation in the absence and presence of the inhibitor, novobiocin. Cotreatment of mitoxantrone with different concentrations of dexamethasone and indomethacin sensitized parental and resistant MCF-7 cells to mitoxantrone cytotoxicity. Dexamethasone increased the accumulation of mitoxantrone in the MCF 7/MX cell line, indicating an inhibition of BCRP. In spite of increased levels of mitoxantrone cytotoxicity in the presence of indomethacin, the accumulation of mitoxantrone was not increased in indomethacin-treated MCF cells. PMID- 20307140 TI - Biochemical evaluation of the protective effect of Aegle marmelos (L.), Corr. leaf extract on tissue antioxidant defense system and histological changes of pancreatic beta-cells in streptozotocin-induced diabetic rats. AB - Oxidative stress is produced under diabetic conditions and is likely involved in the progression of pancreatic damage found in diabetes. This study was undertaken to evaluate the protective effect of Aegle marmelos leaf extract, a medicinal plant, on the tissue antioxidant defense system and lipid peroxidative status in streptozotocin-induced diabetic rats. Ethanol extract of A. marmelos was administered orally for 30 days (150 mg/kg body weight/day) to diabetic rats. Activity of the three primary scavenger enzymes (superoxide dismutase, catalase, and glutathione peroxidase), levels of glutathione, and lipid peroxidation were estimated in plasma and pancreas of diabetic rats and compared to the reference drug, glibenclamide (600 microg/kg body weight/day). A significant increase in the levels of plasma glucose, vitamin E, ceruloplasmin, lipid peroxides, and a concomitant decrease in the levels of vitamin C and reduced glutathione were observed in diabetic rats. The activities of antioxidant enzymes were altered in diabetic rats. These alterations were reverted back to near normal levels after treatment with A. marmelos and glibenclamide. Histopathological studies also revealed the protective effect of A. marmelos on pancreatic beta-cells. The present study indicates that extract of A. marmelos modulates the activity of enzymic and nonenzymic antioxidants and enhances the defense against reactive oxygen species-generated damage in diabetic rats. PMID- 20307141 TI - Pathology Working Group review and evaluation of proliferative lesions of mammary gland tissues in female rats fed ammonium perfluorooctanoate (APFO) in the diet for 2 years. AB - Perfluorooctanoate (PFO) is a perfluorinated carboxylate that is widely distributed in the environment. A 2-year chronic study was conducted in rats fed either 30 or 300 ppm of ammonium perfluorooctanoate (APFO). To investigate the possible relationship of APFO exposure to proliferative mammary lesions, a Pathology Working Group (PWG) review of the original slides was performed. The consensus reached by the PWG was that the incidence of mammary-gland neoplasms was not affected by chronic dietary administration of APFO. Therefore, feeding female rats up to 300 ppm of APFO resulted in no increase in proliferative lesions of the mammary tissue. PMID- 20307142 TI - Behavioral and morphological endpoints: as an early response to sublethal malathion intoxication in the freshwater fish, Labeo rohita. AB - A short-term definitive test by the static renewal bioassay method was conducted to determine the acute toxicity (LC(50)) of commercial-grade organophosphate insecticide, malathion (50% EC) on the freshwater fish, Labeo rohita. Carp fingerlings were exposed to different concentrations of malathion for 96 hours. The acute toxicity (LC(50)) of malathion was found to be 4.5 microg/L. One tenth (1/10, 0.45 microg/L) of the acute toxicity value was selected as the sublethal concentration for subacute studies. The fish were exposed to sublethal concentration for 1, 5, 10, and 15 days and allowed to recover in toxicant-free medium for 15 days. Behavioral responses and morphological deformities were studied in the experimental tenures. Fish in toxic media exhibited irregular, random, circular swimming movements, hyperexcitability, loss of equilibrium, and sinking to the bottom. Caudal bending was the prime morphological malformation. The behavioral and morphological deformities were due to inhibition of acetylcholinesterase (AChE) activity. Inhibition of AChE activity results in excess accumulation of acetylcholine in cholinergic synapses, leading to hyperstimulation and cessation of neuronal transmission (i.e., paralysis). The carp were found under stress, but mortality was insignificant at the sublethal concentration tested. Impaired behavioral responses and morphological deformities were observed during recovery. This may be a consequence due to inhibition of brain and muscular AChE by malaoxon, via the biotransformation of sequestered malathion. PMID- 20307143 TI - Relations between toxicity and altered tissue distribution and urinary excretion of nicotine, cotinine, and hydroxycotinine after chronic oral administration of nicotine in rats. AB - Tissue distribution and urinary excretion of nicotine, cotinine, and hydroxycotinine after multiple oral administration of nicotine to rats for 4 weeks were studied. Physiological change and serum biochemical parameters were also measured to check dysfunction of organs. Significant change of glutathione S transferase, aspartate aminotransferase, blood urea nitrogen, and physiological parameters indicated the toxicity in liver and kidney, at the dose of 5 and 10 mg/kg/day. Only the concentration and total amount of cotinine, not nicotine or hydroxycotinine, in the liver and the kidney showed a proportional dose-dependent increase and were highly correlated with toxicity. Saturation of metabolizing enzymes for nicotine was estimated by the change of urinary excreted amount ratio between nicotine and its metabolites. Metabolizing enzyme to produce cotinine from nicotine was saturated after multiple oral dosing for 4 weeks in a low dose (1 mg/kg/day), but within 1 week in the dose of 5 and 10 mg/kg/day. PMID- 20307144 TI - Chlorophytum borivilianum as potential terminator of free radicals in various in vitro oxidation systems. AB - Chlorophytum borivilianum is a very popular herb in traditional Indian medicine and used as a potent "Rasayana" drug in "Ayurveda" as a rejuvenator. Currently, a large body of evidence supports the key role of free radicals in diverse pathological conditions such as aging and atherosclerosis. The present investigation essentially focuses on the comprehensive account of in vitro antioxidant activity exerted by C.borivilianum root extracts (i.e., aqueous and ethanolic), to clarify the pharmacological antagonism of chemicals/metals mediated oxidation. Graded-dose (25 to 1000 microg/ml) of aqueous extract exhibited higher antioxidant potency as evidenced by powerful nitric oxide, superoxide, hydroxyl, DPPH and ABTS(*+) radicals scavenging activity along with reducing capacity (Fe(3+)/ferricyanide complex and FRAP assays), metal chelating ability, as well as markedly suppressed the lipid peroxidation in mitochondrial fractions as compared to ethanolic extract. Further, aqueous extract significantly decreased (P < 0.05) copper-mediated human serum and kinetics of LDL oxidation, as demonstrated by prolongation of lag phase time with decline of oxidation rate, conjugated dienes, lipid hydroperoxides and thiobarbituric acid reactive substances. In addition, the total polyphenol and flavonoid contents of aqueous extract were higher than that of ethanolic extract, which indicated a positive correlation between antioxidant activity and contents of total phenols. The IC(50) values of both extracts were also compared with appropriate antioxidant standards. Overall, aqueous extract of C.borivilianum root has significant powerful antioxidant activity and may favorably affect atherosclerosis risk status by reducing LDL oxidation susceptibility. PMID- 20307145 TI - Structure elucidation and inhibitory effects of self-assembled organotin(IV) esters of p-tolyl acetic acid on bacterial, fungal, brine shrimp, and potato tumor cells. AB - Biologically active new organotin(IV) acetates (1-6) of p-tolyl acetic acid have been synthesized and characterized by multinuclear nuclear magnetic resonance ((1)H, (13)C) and mass spectrometry. The X-ray crystallographic data of compounds (3 and 4) were also collected. These studies show that in diorganotin(IV) compounds (compounds 1, 2, 3, and 6), tin exists in skew trapezoidal geometry with four strong and two weaker bonds, whereas triorganotin(IV) carboxylates (compounds 4 and 5) have four and five coordinated geometries in solution and solid form, respectively. These compounds were screened for a range of biological activities. Antibacterial activities were determined against six pathogenic bacterial strains, three Gram-positive and three Gram-negative; the activities were measured in terms of inhibition zones (mm). Antifungal activities were determined against six pathogenic fungal strains, cytotoxicity by the brine shrimp lethality assay, and antitumor activities by the crown gall tumor inhibition (potato disc) assay. PMID- 20307146 TI - Assessment of cytotoxic and clastogenic effects of nimesulide: an NSAID drug in somatic cells of BALB/c mice in vivo. AB - The in vivo genotoxicity of nimesulide, a sulfononilide nonsteroidal anti inflammatory drug (NSAID) with anti-inflammatory, analgesic, and antipyretic effects, was evaluated by employing a mouse in vivo chromosomal aberration test in bone marrow cells. Oral treatment of animals for 5 consecutive days with 1, 2.5, 5, and 7.5 mg/kg body weight of the drug resulted in a statistically nonsignificant reduction in mitotic index and increase in CAs/cell and percent abnormal metaphase. The results indicated that nimesulide does not induce cytotoxicity and is a weak clastogen in the bone marrow cells of the mouse in vivo. Thus, the drug presents a very weak genotoxic risk. PMID- 20307147 TI - Melatonin protection on mercury-exerted brain toxicity in the rat. AB - The effect of melatonin on the neurotoxicity induced by mercuric chloride was studied. Adult rats were fed orally with two different doses of mercuric chloride (2 mg; 4 mg/kg body weight) to evaluate brain toxicity with respect to cerebral hemisphere, cerebellum, and medulla oblongata regions for 60 days with or without supplementation with melatonin (5 mg/kg body weight) intraperitoneally. The results suggest that the graded doses of mercury elicit the depletion of enzymatic activities, such as adenosine triphosphatase, succinate dehydrogenase, phosphorylase, alkaline phosphatase, acid phosphatase, altered glycogen, total protein, and lipid peroxidation levels in the cerebral hemisphere, cerebellum, and medulla oblongata of the brain, thereby affecting their respective functions. Blood glucose and mercury levels increased, followed by a reduction in body and organ weights. All these effects seemed to be severe in the cerebral hemisphere of the brain. Further affected indices were, to some extent, maintained in the brain of animals cotreated with melatonin, showing its protective role against mercury-exerted neurotoxicity. PMID- 20307148 TI - Acute renal failure with acyclovir treatment in a child with leukemia. AB - Acyclovir is an effective, frequently used antiviral agent. Adverse effects of this drug are well known and are especially seen with high doses and/or dehydration. In this article, we report a 6-year-old boy with leukemia with nonoliguric acute renal failure in normal hydration status after using acyclovir treatment. He had no preexisting renal impairment, and there were no additional symptoms. Dimercaptosuccinic acid radionucleid scyntigraphy and other laboratory findings revealed impairment of proximal tubule function, in addition to distal tubule. We emphasize that renal functions should be monitored carefully during treatment with acyclovir, and asymptomatic nephrotoxicity must be kept in mind. PMID- 20307149 TI - Evaluation of salidroside in vitro and in vivo genotoxicity. AB - It is reported that salidroside, the main component of a traditional Chinese medicine, Rhodiola rosea, has the efficacy of protecting Coxsackie virus impairment. As part of a safety evaluation on salidroside for use in the treatment of viral myocarditis, the present study evaluated potential genotoxicity of salidroside by using the standard battery of tests (i.e., bacterial reverse mutation assay, chromosomal aberrations assay, and mouse micronucleus assay) recommended by the State Food and Drug Administration of China. The results showed that salidroside was not genotoxic under the conditions of the reverse mutation assay, chromosomal aberrations assay, and mouse micronucleus assay conditions. The anticipated clinical dose seems to be smaller than the doses administered in the genotoxicity assays. With confirmation from further toxicity studies, salidroside would hopefully prove to be a safe anti Coxsackie virus agent. PMID- 20307150 TI - Epithelial healing in experimental corneal alkali wounds with nondiluted autologous serum eye drops. AB - PURPOSE: To evaluate the effects of the topical application of nondiluted autologous serum on epithelial healing as an adjuvant therapy in rabbit corneal alkali wounds. METHODS: Central corneal alkali wounds were produced on the right eye of 16 rabbits, by a 60-second application of a 6-mm round filter paper soaked in 1 N sodium hydroxide (NaOH). One group of rabbits (n=8) was treated with non diluted autologous serum, the other control group (n=8) was treated with physiologic saline, topically 4 times a day. The epithelial healing of the wounds was followed on a slit lamp with and without fluorescein staining daily for 1 week. On day 7, both corneas of each rabbit were excised and assessed histopathologically. RESULTS: A significant increase in the epithelial healing rate was observed in the autologous serum-treated corneas compared with the controls. Epithelial hyperplasia was noticed in specimens with thickened surface cells with multilayers, revealing disorganization in both groups. The autologous serum-treated epithelium showed a relatively well-organized appearance. CONCLUSION: Nondiluted autologous serum eye drops could be used as an adjuvant therapy for promoting the epithelial healing process during the repair stage of corneal alkali wounds. PMID- 20307151 TI - The marketing of pharmaceutical agents: friend or foe? AB - OBJECTIVE: The aim of this paper is to provide a viewpoint regarding the marketing of pharmaceutical agents to psychiatrists and examine the results of a brief survey of the nature of booths, and gifts they offered, during 2009 RANZCP Congress in Adelaide. CONCLUSIONS: The pharmaceutical industry is highly organized and scientifically sophisticated. Efforts to influence our prescribing are likely to have a proven scientific base and to be responsive to evidence. PMID- 20307152 TI - College activities and the ethics of advertising. AB - OBJECTIVES: The aim of this paper is to examine whether advertising in the College journals and at RANZCP Congress, in particular from pharmaceutical companies, gives rise to a conflict of interests, and to discuss how this should be managed. CONCLUSIONS: While advertising will often represent a conflict of interests, banning advertising from the College journals or Congress is unlikely to the best way to manage this. Conflicts of interest may be better managed by development of clear policies on advertisements, broadening the advertising base (i.e. beyond pharmaceutical companies), checking the accuracy of advertisements, and, in the case of Congress, ceasing sponsored symposia. PMID- 20307156 TI - Euphemisms, political correctness and the identity of psychiatrists. PMID- 20307157 TI - Post-exam blues. PMID- 20307158 TI - The case against case histories. PMID- 20307163 TI - Synapse regression in depression: the role of 5-HT receptors in modulating NMDA receptor function and synaptic plasticity. AB - Depression is accompanied by an increase in activity in the amygdala and a decrease in the rostral anterior cingulate cortex (rACC), with the former attributed to a failure of the latter to exert its normal inhibitory influence. This failure is likely due to regression of synaptic connections between the rACC and the amygdala, a process reversed in part by selective serotonin reuptake inhibitors (SSRIs). The present work presents a hypothesis as to how SSRIs might bring about this process and hence normalization of activity, at least in patients that are responsive to SSRIs. Serotonin receptors of the excitatory 5 HT(2A)R class increase N-methyl-D-aspartate receptor (NMDAR) efficacy, while those of the inhibitory 5-HT(1A)R class decrease NMDAR efficacy. A decrease of 5 HT transporter (5-HTT) efficacy, either during human development through functional polymorphisms, or in animals through 5-HTT transgenic knockouts, is accompanied by a decrease in 5-HT(1A)R and hence an increase in excitability and NMDAR efficacy which drives an increase in synaptic spines in the amygdala. As the limbic region of the brain normally possesses high levels of 5-HT(1A)R the effect of loss of these is to increase excitation in this region, as is observed. Changes in the level of extracellular 5-HT in adult animals also modulates the density of synaptic spines, with these increasing with an increase in 5-HT, possibly as a consequence of increases in 5-HT(2A)R activity over that of 5 HT(1A)R. Increasing extracellular levels of 5-HT with SSRIs would then lead to an increase in excitability and in synaptic spines for afferents in the dorsal rostral anterior cingulate cortex but not in the ventral regions such as the amygdala that have few 5-HT(2A)R. This allows dorsal regions to once more exert their inhibitory influence over ventral regions. In this way, SSRIs may exert their effect in normalizing dorsal hypometabolism and ventral hypermetabolism in those suffering from depression. PMID- 20307164 TI - The Kessler Psychological Distress Scale in Te Rau Hinengaro: the New Zealand Mental Health Survey. AB - OBJECTIVE: The aim of the present study was to compare two versions of the Kessler 10-item scale (K10), as measures of population mental health status in New Zealand. METHOD: A nationwide household survey of residents aged > or = 16 years was carried out between 2003 and 2004. The World Mental Health Composite International Diagnostic Interview (CIDI 3.0) was used to obtain DSM-IV diagnoses. Serious mental illness (SMI) was defined as for the World Mental Health Surveys Initiative and the USA National Comorbidity Survey Replication. Participants were randomly assigned to receive the 'past month' K10 or the 'worst month in the past 12 months' K10. There were 12 992 completed interviews; 7435 included the K10. The overall response rate was 73.3%. Receiver operator characteristic (ROC) curves were used to examine the ability of both K10 versions to discriminate between CIDI 3.0 cases and non-cases, and to predict SMI. RESULTS: Scores on both versions of the K10 were higher for female subjects, younger people, people with fewer educational qualifications, people with lower household income and people resident in more socioeconomically deprived areas. Both versions of the K10 were effective in discriminating between CIDI 3.0 cases and non-cases for anxiety disorder, mood disorders and any study disorder. The worst month in the past 12 months K10 is a more effective predictor than the past 1 month K10 of SMI (area under the curve: 0.89 vs 0.80). CONCLUSIONS: Either version of the K10 could be used in repeated health surveys to monitor the mental health status of the New Zealand population and to derive proxy prevalence estimates for SMI. The worst month in the past 12 months K10 may be the preferred version in such surveys, because it is a better predictor of SMI than the past month K10 and also has a more logical relationship to 12 month disorder and 12 month service use. PMID- 20307165 TI - Psychopathology and symptom remission at adolescence among children with attention-deficit-hyperactivity disorder. AB - OBJECTIVE: The aim of the present study was to examine changes of attention deficit-hyperactivity disorder (ADHD) symptoms and psychiatric comorbidities at adolescence, and mother-child agreement on reports of ADHD symptoms among children with ADHD as compared to unaffected controls. METHODS: The participants included 93 patients (male, 82.8%) aged 11-16, who were clinically diagnosed with ADHD at the mean age of 7.3 +/- 2.8 years, and 93 age-, sex-, and parental education-matched school controls. The participants and their mothers were first interviewed separately for baseline psychopathology at childhood, followed by current psychopathology using the Chinese Kiddie Epidemiologic version of the Schedule for Affective Disorders and Schizophrenia. RESULTS: At adolescence, 46 patients (49.5%) met full DSM-IV ADHD criteria, 31 (33.3%) had subthreshold ADHD, and 16 (17.2%) had recovered from ADHD. We found a significant progressive decline in the three ADHD core symptoms for the ADHD group: hyperactivity had the greatest effect size, followed by inattention, and then impulsivity. Children with ADHD tended to report less severe ADHD symptoms at childhood and adolescence than their mothers. They were more likely than the controls to have oppositional defiant disorder (odds ratio (OR)=18.0; 95% confidence interval (CI)=8.3-38.9), conduct disorder (OR=23.1, 95%CI =5.3-100.2), mood disorders (OR=3.8, 95%CI = 1.5 9.4), bipolar disorders (Fisher's exact p < 0.001), and sleep disorders (OR=3.1, 95%CI = 1.6-6.0) at adolescence. CONCLUSIONS: The present findings are similar to those of Western studies, regarding the patterns of comorbidity, stability of core symptoms, and mother-child differences on symptom reports. PMID- 20307166 TI - Cigarette smoking and psychosis: naturalistic follow up 4 years after an intervention trial. AB - OBJECTIVE: Cigarette smoking is very common among people with a psychotic disorder and is often not addressed by clinicians. Additionally, few studies have evaluated smoking interventions among this group. The present study reports findings from a naturalistic follow up 4 years after a smoking intervention trial. METHOD: Longer-term smoking, symptomatology and functioning were examined among 247 participants (recruited in Sydney and Newcastle, Australia) who initially attended a 1 year follow up of an eight-session individually administered trial for regular smokers with a psychotic disorder. Variables profiled included continuous and point prevalence abstinence rates, smoking reduction status (no reduction, < 50%, > or = 50%, or abstinence) and changes in anxiety, depression and current functioning. RESULTS: Two-thirds of those who completed the 1 year assessment were followed up at 4 years (164/247, 66.4%), of whom 79.2% reported maintenance or improvement in their smoking reduction status relative to 1 year. Abstinence at 1 year was significantly associated with 4 year point prevalence abstinence. Lengthy periods of abstinence were also evident among those reporting 4 year point prevalence abstinence or at least a 50% reduction. No baseline or intervention status variables predicted smoking status at 4 years. Symptomatology and functioning also improved between baseline and 4 years. CONCLUSIONS: Smokers with a psychotic disorder are capable of long-term change. It is recommended that clinicians address and monitor smoking during treatment of people with psychosis, emphasizing potential lifestyle and harm reduction benefits, with a view to eventual smoking cessation. PMID- 20307167 TI - Comparison of the prevalence of mental health problems in deaf and hearing children and adolescents in Australia. AB - OBJECTIVE: The aims of the present study were to (i) identify the prevalence rate and nature of mental health problems in a group of Australian deaf children and adolescents and compare these to those reported for the Australian hearing population; and (ii) identify specific demographic characteristics that may typify deaf children and adolescents with mental health problems. METHOD: Sixty six parents of deaf children and adolescents aged 6-18 years, their teachers and 38 adolescents participated in the study. Data related to mental health problems were collected using the Child Behaviour Checklist and Youth Self-Report. Data related to demographic characteristics were obtained via parent and teacher surveys. RESULTS: The overall prevalence rate of mental health problems reported by parents and adolescents in the present study is comparable to that of the Australian hearing population. Parents in the present study, however, reported significantly more concerns on the social problem and thought problem scales than did Australian parents of hearing children and adolescents. There were also significant differences between the prevalence and nature of mental health problems as reported by the deaf adolescents in the present study when compared to deaf adolescents in another Australian study. These differences appear to be explained by differences in the preferred communication mode of the participants in the two studies. CONCLUSIONS: The known heterogeneity within the Australian deaf child and adolescent population with respect to preferred mode of communication has important implications not only for the appropriate selection and use of psychiatric instruments in assessing child and adolescent mental health but also for the accurate reporting of the prevalence and nature of mental health problems within this population. PMID- 20307168 TI - Recent declines in Australian male suicide are real, not artefactual. AB - OBJECTIVES: The aim of the present study was to clarify the extent to which the recorded marked decline in young male suicide (20-34 years) in Australia since 1998 is attributable to misclassification of cause of death information. METHODS: Secular trends in young male suicide rates were investigated for the period 1976 2005. Suicide rates in the period after the peak of the epidemic in this age group (1998) were re-calculated based on published estimates of under-enumeration of suicide data, and misclassification of likely suicide cases to other unintentional and undetermined external causes. Two misclassification scenarios were used to revise young male suicide rates from 1998: previously reported estimates of 9% under-enumeration due to misclassification of unintentional causes of death, and 17% under-enumeration due to misclassification of open cases in addition to unintentional causes of death. All-cause mortality was also examined. RESULTS: Recorded male suicide in the 20-34 year age group increased over the study period, peaking in 1998 at 39 per 100,000, before declining sharply in the period 1999-2005 by 44% to 22 per 100,000 in 2005. Following adjustment for misallocation under the first scenario, suicide rates declined 38% to 24 per 100,000, and under the second scenario declined 33% to 26 per 100,000. Revised suicide rates were not materially different from recorded suicide rates based on 95% confidence intervals over this period. All-cause mortality declined from 1999 due to reductions in suicide and other causes. CONCLUSION: The recent marked decline in young male suicide in Australia is real. The effects of misallocation of likely suicide cases to other causes did not substantially affect population trends in suicide rates in the period after 1998. There is still a need to account in detail for why young male suicide has declined so substantially during the period after 1998. PMID- 20307169 TI - Executive functions and memory abilities in children with 22q11.2 deletion syndrome. AB - OBJECTIVE: Velo-cardio-facial syndrome or 22q11.2 deletion syndrome (22q11DS) is the most common known microdeletion syndrome. One of the genes in the deleted region is the catechol-O-methyltransferase (COMT) gene, which is thought to have significant effects on cognition through its influence on dopamine metabolism. The aim of the present study was to better characterize the cognitive phenotype in a large cohort children with 22q11DS compared with sibling controls and to investigate if the cognitive deficits in 22q11DS were modulated by COMT expression. METHOD: The memory, executive function and attentional abilities of children with 22q11DS (n = 50) compared to sibling controls (n = 31), were measured. Also, within children with 22q11DS, a preliminary exploration was carried out of the relationship between cognitive ability and COMT genotype. RESULTS: Overall, the 22q11DS group had significantly reduced scores on tests of memory (especially in visual memory) and executive function (particularly in planning, working memory, and motor organization) compared with sibling controls. No association, however, was identified between COMT genotype and cognitive function. CONCLUSIONS: Although 22q11DS children have specific cognitive deficits, differences in COMT do not account for these findings. PMID- 20307170 TI - Patterns of antipsychotic medication use in Australia 2002-2007. AB - OBJECTIVE: Atypical antipsychotic medications that are primarily used to treat schizophrenia and bipolar disorder cost the Pharmaceutical Benefits Scheme (PBS) AUD$334.4m in 2007. There are indications that they have also been used outside the approved indications to treat behavioural disturbances in the elderly. The aim of the present study was therefore to examine (i) trends in prescribing of subsidized atypical antipsychotic drugs in the Australian population from 2002 to 2007; and (ii) gender and age differences in the utilization of these drugs. METHODS: Government (Medicare Australia) data on numbers of prescriptions, quantity and doses for atypical and typical antipsychotics from 2002 to 2007 were analysed. Defined daily dose per 1000 population per day were estimated for age and sex groups using Australian Bureau of Statistics population data. RESULTS: The proportion of prescribed antipsychotics that were atypical increased from 61% in 2002 to 77% in 2007. In male subjects, olanzapine was most often prescribed between the ages of 25 and 55 years. In female subjects, in contrast, the highest rates of prescribing were in those > or = 75 years. Lower doses of these drugs were prescribed in older adults. CONCLUSIONS: Atypical antipsychotic drugs were most commonly used to treat schizophrenia in younger men and behavioural disturbances in older women with dementia. They appear to have been used outside of the approved indication for schizophrenia and bipolar disorder with significant financial costs to the PBS. Research into the reasons for their extensive use in elderly women is needed to inform more rational prescribing of these medicines. PMID- 20307171 TI - Does socioeconomic inequality explain ethnic differences in nicotine dependence? Evidence from a New Zealand birth cohort. AB - OBJECTIVE: The present study examined the role of socioeconomic status and cultural identity in the association between ethnicity and nicotine dependence, in a birth cohort of >1000 methods young people studied to age 30. METHODS: Data were gathered on ethnicity, cultural identification, nicotine dependence, and socioeconomic factors, as part of a longitudinal study of a New Zealand birth cohort (the Christchurch Health and Development Study). RESULTS: Those reporting Maori identity had rates of nicotine dependence that were significantly higher (p < 0.05) than rates for non-Maori. Control for socioeconomic factors reduced the associations between ethnic identity and nicotine dependence to statistical non significance. In addition, there was no evidence of a statistically significant association between Maori cultural identity and nicotine dependence, nor was there evidence of gender differences in the association between ethnic identity and nicotine dependence, after controlling for socioeconomic factors. CONCLUSIONS: The higher rates of nicotine dependence observed among Maori appear to be attributable to differences in socioeconomic status. Efforts to improve the socioeconomic standing of Maori should therefore help to reduce rates of nicotine dependence in this population. PMID- 20307172 TI - Vulnerability factors for disaster-induced child post-traumatic stress disorder: the case for low family resilience and previous mental illness. AB - OBJECTIVE: The aim of the present study was to investigate whether parent report of family resilience predicted children's disaster-induced post-traumatic stress disorder (PTSD) and general emotional symptoms, independent of a broad range of variables including event-related factors, previous child mental illness and social connectedness. METHODS: A total of 568 children (mean age = 10.2 years, SD = 1.3) who attended public primary schools, were screened 3 months after Cyclone Larry devastated the Innisfail region of North Queensland. Measures included parent report on the Family Resilience Measure and Strengths and Difficulties Questionnaire (SDQ)-emotional subscale and child report on the PTSD Reaction Index, measures of event exposure and social connectedness. RESULTS: Sixty-four students (11.3%) were in the severe-very severe PTSD category and 53 families (28.6%) scored in the poor family resilience range. A lower family resilience score was associated with child emotional problems on the SDQ and longer duration of previous child mental health difficulties, but not disaster-induced child PTSD or child threat perception on either bivariate analysis, or as a main or moderator variable on multivariate analysis (main effect: adjusted odds ratio (OR(adj)) = 0.57, 95% confidence interval (CI) = 0.13-2.44). Similarly, previous mental illness was not a significant predictor of child PTSD in the multivariate model (OR(adj) = 0.75, 95%CI = 0.16-3.61). CONCLUSION: In this post-disaster sample children with existing mental health problems and those of low-resilience families were not at elevated risk of PTSD. The possibility that the aetiological model of disaster-induced child PTSD may differ from usual child and adolescent conceptualizations is discussed. PMID- 20307173 TI - Monitoring of patients on a community treatment order. PMID- 20307174 TI - Heritability of epigenetic effects. PMID- 20307175 TI - Mania as a presentation of acute demyelination in an adolescent girl. PMID- 20307176 TI - Bipolar affective disorder presenting as failure of parenting. PMID- 20307177 TI - Panhypopituitarism and psychosis in a male patient. PMID- 20307178 TI - The astrobiology habitability primer. PMID- 20307179 TI - The search for worlds like our own. AB - The direct detection of Earth-like exoplanets orbiting nearby stars and the characterization of such planets-particularly, their evolution, their atmospheres, and their ability to host life-constitute a significant problem. The quest for other worlds as abodes of life has been one of mankind's great questions for several millennia. For instance, as stated by Epicurus approximately 300 BC: "Other worlds, with plants and other living things, some of them similar and some of them different from ours, must exist." Demokritos from Abdera (460-370 BC), the man who invented the concept of indivisible small parts atoms-also held the belief that other worlds exist around the stars and that some of these worlds may be inhabited by life-forms. The idea of the plurality of worlds and of life on them has since been held by scientists like Johannes Kepler and William Herschel, among many others. Here, one must also mention Giordano Bruno. Born in 1548, Bruno studied in France and came into contact with the teachings of Nicolas Copernicus. He wrote the book De l'Infinito, Universo e Mondi in 1584, in which he claimed that the Universe was infinite, that it contained an infinite amount of worlds like Earth, and that these worlds were inhabited by intelligent beings. At the time, this was extremely controversial, and eventually Bruno was arrested by the church and burned at the stake in Rome in 1600, as a heretic, for promoting this and other equally confrontational issues (though it is unclear exactly which idea was the one that ultimately brought him to his end). In all the aforementioned cases, the opinions and results were arrived at through reasoning-not by experiment. We have only recently acquired the technological capability to observe planets orbiting stars other than 6 our Sun; acquisition of this capability has been a remarkable feat of our time. We show in this introduction to the Habitability Primer that mankind is at the dawning of an age when, by way of the scientific method and 21(st) century technology, we will be able to answer this fascinating controversial issue that has persisted for at least 2500 years. PMID- 20307180 TI - Origin and formation of planetary systems. AB - To estimate the occurrence of terrestrial exoplanets and maximize the chance of finding them, it is crucial to understand the formation of planetary systems in general and that of terrestrial planets in particular. We show that a reliable formation theory should not only explain the formation of the Solar System, with small terrestrial planets within a few AU and gas giants farther out, but also the newly discovered exoplanetary systems with close-in giant planets. Regarding the presently known exoplanets, we stress that our current knowledge is strongly biased by the sensitivity limits of current detection techniques (mainly the radial velocity method). With time and improved detection methods, the diversity of planets and orbits in exoplanetary systems will definitely increase and help to constrain the formation theory further. In this work, we review the latest state of planetary formation in relation to the origin and evolution of habitable terrestrial planets. PMID- 20307181 TI - Dynamical habitability of planetary systems. AB - The problem of the stability of planetary systems, a question that concerns only multiplanetary systems that host at least two planets, is discussed. The problem of mean motion resonances is addressed prior to discussion of the dynamical structure of the more than 350 known planets. The difference with regard to our own Solar System with eight planets on low eccentricity is evident in that 60% of the known extrasolar planets have orbits with eccentricity e > 0.2. We theoretically highlight the studies concerning possible terrestrial planets in systems with a Jupiter-like planet. We emphasize that an orbit of a particular nature only will keep a planet within the habitable zone around a host star with respect to the semimajor axis and its eccentricity. In addition, some results are given for individual systems (e.g., Gl777A) with regard to the stability of orbits within habitable zones. We also review what is known about the orbits of planets in double-star systems around only one component (e.g., gamma Cephei) and around both stars (e.g., eclipsing binaries). PMID- 20307182 TI - Geophysical and atmospheric evolution of habitable planets. AB - The evolution of Earth-like habitable planets is a complex process that depends on the geodynamical and geophysical environments. In particular, it is necessary that plate tectonics remain active over billions of years. These geophysically active environments are strongly coupled to a planet's host star parameters, such as mass, luminosity and activity, orbit location of the habitable zone, and the planet's initial water inventory. Depending on the host star's radiation and particle flux evolution, the composition in the thermosphere, and the availability of an active magnetic dynamo, the atmospheres of Earth-like planets within their habitable zones are differently affected due to thermal and nonthermal escape processes. For some planets, strong atmospheric escape could even effect the stability of the atmosphere. PMID- 20307183 TI - Origin and evolution of life on terrestrial planets. AB - The ultimate goal of terrestrial planet-finding missions is not only to discover terrestrial exoplanets inside the habitable zone (HZ) of their host stars but also to address the major question as to whether life may have evolved on a habitable Earth-like exoplanet outside our Solar System. We note that the chemical evolution that finally led to the origin of life on Earth must be studied if we hope to understand the principles of how life might evolve on other terrestrial planets in the Universe. This is not just an anthropocentric point of view: the basic ingredients of terrestrial life, that is, reduced carbon-based molecules and liquid H(2)O, have very specific properties. We discuss the origin of life from the chemical evolution of its precursors to the earliest life-forms and the biological implications of the stellar radiation and energetic particle environments. Likewise, the study of the biological evolution that has generated the various life-forms on Earth provides clues toward the understanding of the interconnectedness of life with its environment. PMID- 20307184 TI - Co-evolution of atmospheres, life, and climate. AB - After Earth's origin, our host star, the Sun, was shining 20-25% less brightly than today. Without greenhouse-like conditions to warm the atmosphere, our early planet would have been an ice ball, and life may never have evolved. But life did evolve, which indicates that greenhouse gases must have been present on early Earth to warm the planet. Evidence from the geological record indicates an abundance of the greenhouse gas CO(2). CH(4) was probably present as well; and, in this regard, methanogenic bacteria, which belong to a diverse group of anaerobic prokaryotes that ferment CO(2) plus H(2) to CH(4), may have contributed to modification of the early atmosphere. Molecular oxygen was not present, as is indicated by the study of rocks from that era, which contain iron carbonate rather than iron oxide. Multicellular organisms originated as cells within colonies that became increasingly specialized. The development of photosynthesis allowed the Sun's energy to be harvested directly by life-forms. The resultant oxygen accumulated in the atmosphere and formed the ozone layer in the upper atmosphere. Aided by the absorption of harmful UV radiation in the ozone layer, life colonized Earth's surface. Our own planet is a very good example of how life forms modified the atmosphere over the planets' lifetime. We show that these facts have to be taken into account when we discover and characterize atmospheres of Earth-like exoplanets. If life has originated and evolved on a planet, then it should be expected that a strong co-evolution occurred between life and the atmosphere, the result of which is the planet's climate. PMID- 20307186 TI - Stellar aspects of habitability--characterizing target stars for terrestrial planet-finding missions. AB - We present and discuss the criteria for selecting potential target stars suitable for the search for Earth-like planets, with a special emphasis on the stellar aspects of habitability. Missions that search for terrestrial exoplanets will explore the presence and habitability of Earth-like exoplanets around several hundred nearby stars, mainly F, G, K, and M stars. The evaluation of the list of potential target systems is essential in order to develop mission concepts for a search for terrestrial exoplanets. Using the Darwin All Sky Star Catalogue (DASSC), we discuss the selection criteria, configuration-dependent subcatalogues, and the implication of stellar activity for habitability. PMID- 20307185 TI - Deciphering spectral fingerprints of habitable exoplanets. AB - We discuss how to read a planet's spectrum to assess its habitability and search for the signatures of a biosphere. After a decade rich in giant exoplanet detections, observation techniques have advanced to a level where we now have the capability to find planets of less than 10 Earth masses (M(Earth)) (so-called "super Earths"), which may be habitable. How can we characterize those planets and assess whether they are habitable? This new field of exoplanet search has shown an extraordinary capacity to combine research in astrophysics, chemistry, biology, and geophysics into a new and exciting interdisciplinary approach to understanding our place in the Universe. The results of a first-generation mission will most likely generate an amazing scope of diverse planets that will set planet formation, evolution, and our planet into an overall context. PMID- 20307187 TI - A roadmap for the detection and characterization of other Earths. AB - The European Space Agency and other space agencies such as NASA recognize that the question with regard to life beyond Earth in general, and the associated issue of the existence and study of exoplanets in particular, is of paramount importance for the 21(st) century. The new Cosmic Vision science plan, Cosmic Vision 2015-2025, which is built around four major themes, has as its first theme: "What are the conditions for planet formation and the emergence of life?" This main theme is addressed through further questions: 1) How do gas and dust give rise to stars and planets? 2) How will the search for and study of exoplanets eventually lead to the detection of life outside Earth (biomarkers)? 3) How did life in the Solar System arise and evolve? Although ESA has busied itself with these issues since the beginning of the Darwin study in 1996, it has become abundantly clear that, as these topics have evolved, only a very large effort, addressed from the ground and from space with the utilization of different instruments and space missions, can provide the empirical results required for a complete understanding. The good news is that the problems can be addressed and solved within a not-too-distant future. In this short essay, we present the present status of a roadmap related to projects that are related to the key long-term goal of understanding and characterizing exoplanets, in particular Earth-like planets. PMID- 20307188 TI - The far future of exoplanet direct characterization. AB - We describe future steps in the direct characterization of habitable exoplanets subsequent to medium and large mission projects currently underway and investigate the benefits of spectroscopic and direct imaging approaches. We show that, after third- and fourth-generation missions have been conducted over the course of the next 100 years, a significant amount of time will lapse before we will have the capability to observe directly the morphology of extrasolar organisms. PMID- 20307189 TI - In vitro cytotoxicity, apoptosis, DNA-binding, and antioxidant activity studies of ruthenium (II) complexes. AB - Two new ligands maip (1) (maip = 2-(3-aminophenyl)imizado[4,5 f][1,10]phenanthroline), paip (2) (paip = 2-(4-aminophenyl)imidazo[4,5 f][1,10]phenanthroline), and their ruthenium (II) complexes [Ru(phen)(2)(maip)](ClO(4))(2) (3) and [Ru(phen)(2)(paip)](ClO(4))(2) (4) (phen = 1,10-phenanthroline) have been synthesized and characterized. The cytotoxicity of these compounds was evaluated by MTT [3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide] assay. The apoptosis assay was carried out with acridine orange/ethidium bromide staining methods. The DNA-binding behaviors of complexes 3 and 4 were investigated by viscosity measurements, thermal denaturation, photocleavage, and spectroscopic methods. The results show that the two complexes intercalate into the base pairs of DNA. In the presence of a complex, apoptosis of BEL-7402 cells was observed. Experiments show that these compounds exhibit antioxidant activity against hydroxyl radicals. PMID- 20307190 TI - Biological variation among african trypanosomes: I. Clonal expression of virulence is not linked to the variant surface glycoprotein or the variant surface glycoprotein gene telomeric expression site. AB - The potential association of variant surface glycoprotein (VSG) gene expression with clonal expression of virulence in African trypanosomes was addressed. Two populations of clonally related trypanosomes, which differ dramatically in virulence for the infected host, but display the same apparent VSG surface coat phenotype, were characterized with respect to the VSG genes expressed as well as the chromosome telomeric expression sites (ES) utilized for VSG gene transcription. The VSG gene sequences expressed by clones LouTat 1 and LouTat 1A of Trypanosoma brucei rhodesiense were identical, and gene expression in both clones occurred precisely by the same gene conversion events (duplication and transposition), which generated an expression-linked copy (ELC) of the VSG gene. The ELC was present on the same genomic restriction fragments in both populations and resided in the telomere of a 330-kb chromosome; a single basic copy of the LouTat 1/1A VSG gene, present in all variants of the LouTat 1 serodeme, was located at an internal site of a 1.5-Mb chromosome. Restriction endonuclease mapping of the ES telomere revealed that the VSG ELC of clones LouTat 1 and 1A resides in the same site. Therefore, these findings provide evidence that the VSG gene ES and, potentially, any cotranscribed ES-associated genes do not play a role in the clonal regulation of virulence because trypanosome clones LouTat 1 and 1A, which differ markedly in their virulence properties, both express identical VSG genes from the same chromosome telomeric ES. PMID- 20307191 TI - Clinical practice guidelines for Clostridium difficile infection in adults: 2010 update by the society for healthcare epidemiology of America (SHEA) and the infectious diseases society of America (IDSA). AB - Since publication of the Society for Healthcare Epidemiology of America position paper on Clostridium difficile infection in 1995, significant changes have occurred in the epidemiology and treatment of this infection. C. difficile remains the most important cause of healthcare-associated diarrhea and is increasingly important as a community pathogen. A more virulent strain of C. difficile has been identified and has been responsible for more-severe cases of disease worldwide. Data reporting the decreased effectiveness of metronidazole in the treatment of severe disease have been published. Despite the increasing quantity of data available, areas of controversy still exist. This guideline updates recommendations regarding epidemiology, diagnosis, treatment, and infection control and environmental management. PMID- 20307192 TI - Adding new chemistries to the genetic code. AB - The development of new orthogonal aminoacyl-tRNA synthetase/tRNA pairs has led to the addition of approximately 70 unnatural amino acids (UAAs) to the genetic codes of Escherichia coli, yeast, and mammalian cells. These UAAs represent a wide range of structures and functions not found in the canonical 20 amino acids and thus provide new opportunities to generate proteins with enhanced or novel properties and probes of protein structure and function. PMID- 20307193 TI - Amphipols, nanodiscs, and fluorinated surfactants: three nonconventional approaches to studying membrane proteins in aqueous solutions. AB - Membrane proteins (MPs) are usually handled in aqueous solutions as protein/detergent complexes. Detergents, however, tend to be inactivating. This situation has prompted the design of alternative surfactants that can be substituted for detergents once target proteins have been extracted from biological membranes and that keep them soluble in aqueous buffers while stabilizing them. The present review focuses on three such systems: Amphipols (APols) are amphipathic polymers that adsorb onto the hydrophobic transmembrane surface of MPs; nanodiscs (NDs) are small patches of lipid bilayer whose rim is stabilized by amphipathic proteins; fluorinated surfactants (FSs) resemble detergents but interfere less than detergents do with stabilizing protein/protein and protein/lipid interactions. The structure and properties of each of these three systems are described, as well as those of the complexes they form with MPs. Their respective usefulness, constraints, and prospects for functional and structural studies of MPs are discussed. PMID- 20307194 TI - Learning disabilities and dying. PMID- 20307195 TI - How oncology fellows discuss transitions in goals of care: a snapshot of approaches used prior to training. AB - INTRODUCTION: The moment when a physician raises the possibility of discontinuing palliative chemotherapy at the end of life is a critical moment in the illness, and a difficult conversation. Expert recommendations cite the importance of giving bad news in these situations but there is limited research addressing how physicians should discuss transitions in goals of care from disease-modifying therapy to end-of-life care. While existing research includes survey data and observational studies of oncologist outpatient visits with patient who have advanced cancer, there are no studies that characterize actual physician communication behaviors when the physician tried to initiate a transitions conversation with a patient who has advanced cancer. METHOD: In this study, we examined the communication approaches used by oncology fellows discussing transitions with a standardized patient using audiorecordings collected prior to an intensive communication skills workshop. In this preworkshop encounter, each oncology fellow had the task of discussing a transition in goals of care with a patient who was experiencing cancer progression despite treatment with existing evidence-based therapies. We used qualitative methodology to characterize the approaches used by oncology fellows in 20 of these pre-workshop conversations. RESULTS: We identified two themes in the approaches that fellows used: (1) the limitations of biomedical disease-modifying treatments and (2) the possibility of a new direction for medical care when disease-modifying treatments have been exhausted. CONCLUSION: We found that for each theme, fellows tended to emphasize a logical frame or an experiential frame. Understanding these frames could be useful in designing future communication skills training interventions. PMID- 20307197 TI - ACB-PCR quantification of K-RAS codon 12 GAT and GTT mutant fraction in colon tumor and non-tumor tissue. AB - K-RAS mutation is being developed as a cancer biomarker and tumor K-RAS is being used to predict therapeutic response. Yet, levels of K-RAS mutation in normal and pathological tissue samples have not been determined rigorously, nor inter individual variation in these levels characterized. Therefore, K-RAS codon 12 GAT and GTT mutant fractions were measured in colonic mucosa of individuals without colon cancer, tumor-distal mucosa, tumor-proximal mucosa, normal tumor-adjacent tissues, colonic adenomas, and carcinomas. The results indicate K-RAS codon 12 GAT mutation is present at measurable levels in normal appearing mucosa. All tumors carried K-RAS mutation, in most cases as a mutant subpopulation. PMID- 20307196 TI - p16 Modulates VEGF expression via its interaction with HIF-1alpha in breast cancer cells. AB - The degree of tumor progression (such as growth, angiogenesis, and metastasis) directly correlates with the expression of vascular endothelial growth factor (VEGF), but inversely correlates with the expression of tumor-suppressor gene p16, therefore we examined whether the restoration of p16 in breast cancer cells would modulate VEGF expression. Adenoviral-mediated p16 expression downregulated VEGF gene expression in breast cancer cells, and inhibited breast cancer cell induced angiogenesis by a dorsal air sac model in mice. Moreover, p16 appears to form a complex with HIF-1a, the transcription factor for the VEGF gene promoter. Taken together, the binding between p16 and HIF-1a protein may alter HIF-1a's ability to transactivate VEGF expression. PMID- 20307198 TI - Combination of fludarabine and imatinib induces apoptosis synergistically through loss of mitochondrial membrane potential and increases in caspase-3 enzyme activity in human K562 chronic myleloid leukemia cells. AB - In this study, we aimed to show the synergistic apoptotic effects of imatinib/fludarabine combination in human K562 chronic myleloid leukemia (CML) cells. There was a significant increase in cytotoxicity of combination of imatinib and fludarabine as compared to any agent alone. On the other hand, combination of both agents induced apoptosis significantly as confirmed by increases in caspase-3 enzyme activity and decreases in mitochondrial membrane potential. As a summary, the results of this study strongly suggest that combination of imatinib and fludarabine induced cell death synergistically comparing to only imatinib or fludarabine in human K562 CML cells. PMID- 20307199 TI - Adjuvant endocrine therapy for early breast cancer: the story so far. AB - Aromatase inhibitors (AIs) have largely replaced tamoxifen as adjuvant hormonal therapy for postmenopausal women with early breast cancer. While tamoxifen is effective in reducing breast cancer recurrence and mortality, recent data indicate two peaks of early, mostly distant metastatic recurrences in patients receiving tamoxifen, and AIs have proven more effective in reducing recurrence. As distant recurrence has been associated with poorer survival and death, reduction in this type of early recurrence event may lead to improved survival over the long term. Recent data from major clinical trials are beginning to bear out this contention. PMID- 20307200 TI - The role of irreversible EGFR inhibitors in the treatment of non-small cell lung cancer: overcoming resistance to reversible EGFR inhibitors. AB - Reversible epidermal growth factor receptor tyrosine kinase inhibitors are often used for the treatment of non-small cell lung cancer following failure of cytotoxic chemotherapy. While these agents are active in a subset of patients, most develop resistance and progress within the course of 1 year. In nearly half of the cases, acquired resistance is caused by a secondary epidermal growth factor receptor T790M mutation. Irreversible epidermal growth factor receptor tyrosine kinase inhibitors are an emerging class of agents that may have the potential to overcome and prevent the emergence of such mutation-related resistance. PMID- 20307201 TI - Assay, preclinical, and clinical brick walls and opportunities for system change through GRANDRx. PMID- 20307202 TI - Do liver IL-12 levels predict sustained response to IFN-alpha therapy in children with chronic hepatitis B? AB - The aim of this study is to investigate the immunoregulatory role of interleukin 12 and interferon-gamma in children with chronic hepatitis B who are treated with interferon-alpha therapy. The patients were divided into 2 groups: Group I included 16 children with naive chronic replicative hepatitis B infection, and Group II included 6 children who are inactive hepatitis B virus (HBV) carriers. Group I received interferon-alpha subcutaneously (10 mU/m(2)/dose), 3 times a week during 4 months. Initial serum alanine aminotransferase (ALT) levels, hepatitis B serologic markers, serum interleukin-12 and interferon-gamma levels were measured. In Group I, laboratory tests were re-evaluated in the second and fourth months. Liver biopsy was performed in all patients and samples were used for tissue interleukin-12 level evaluation and histopathological examination. Hepatic activity index (HAI) and serum interferon-gamma were significantly higher in Group I (P < 0.05). Initial tissue interleukin-12 levels in Group I were low but a significant increase was observed at the fourth month (P < 0.05). While responder patients in Group I had marked elevation of tissue interleukin-12 levels, nonresponders did not reveal considerable changes at the fourth month evaluation. A negative correlation was found between serum HBV-DNA copies and interferon-gamma levels prior to therapy (P < 0.01, r: -0.66). The analysis of cytokine levels with serum transaminases demonstrated a positive correlation between the tissue interleukin-12 levels at the fourth month and serum ALT levels at the beginning and second month of the therapy (r: 0.77, P < 0.05 and r: 0.92, P < 0.05, respectively). This is the first study emphasizing the relationship between tissue cytokine levels and therapy success. Understanding the course of chronic hepatits B in the pediatric population will help us to clarify some debates on the treatment. PMID- 20307203 TI - When is correlation coevolution? AB - Studying the correlation between traits of interacting species has long been a popular approach for identifying putative cases of coevolution. More recently, such approaches have been used as a means to evaluate support for the geographic mosaic theory of coevolution. Here we examine the utility of these approaches, using mathematical and computational models to predict the correlation that evolves between traits of interacting species for a broad range of interaction types. Our results reveal that coevolution is neither a necessary nor a sufficient condition for the evolution of spatially correlated traits between two species. Specifically, our results show that coevolutionary selection fails to consistently generate statistically significant correlations and, conversely, that non-coevolutionary processes can readily cause statistically significant correlations to evolve. In addition, our results demonstrate that studies of trait correlations per se cannot be used as evidence either for or against a geographic mosaic process. Taken together, our results suggest that understanding the coevolutionary process in natural populations will require detailed mechanistic studies conducted in multiple populations or the use of more sophisticated statistical approaches that better use information contained in existing data sets. PMID- 20307204 TI - Sequential acquisition of human papillomavirus (HPV) infection of the anus and cervix: the Hawaii HPV Cohort Study. AB - BACKGROUND: Relatively little is known about the epidemiology of anal human papillomavirus (HPV) infection in healthy women and its association with cervical HPV infection. METHODS: he association of an incident cervical (or anal) HPV infection with the subsequent risk of a genotype-concordant incident anal (or cervical) HPV infection was examined in a longitudinal cohort study of 751 sexually active women. Age-adjusted hazard ratios, obtained using Cox regression, served as measurements of relative risk (RR). RESULTS: Among women, the RR of acquiring an anal HPV infection after a cervical infection with HPV of the same genotype was 20.5 (95% confidence interval, 16.3-25.7), and the RR of acquiring a cervical HPV infection after an anal infection with HPV of the same genotype was 8.8 (95% confidence interval, 6.4-12.2), compared with women without a previous anal/cervical infection with HPV of a concordant genotype. RRs varied by phylogenetic species, with HPV alpha3/alpha15 and alpha1/alpha8/alpha10 types having a greater likelihood than other types of HPV infecting the anus among women with a previous infection at the cervix with HPV of the same genotype. CONCLUSIONS: It appears common for anal and cervical HPV infections to occur consecutively. The high degree of genotype-specific concordance suggests that the cervix (vagina) and anus may serve as reservoirs for HPV infection at the other anatomical site. PMID- 20307205 TI - Large urban outbreak of orally acquired acute Chagas disease at a school in Caracas, Venezuela. AB - BACKGROUND: Trypanosoma cruzi oral transmission is possible through food contamination by vector's feces. Little is known about the epidemiology and clinical features of microepidemics of orally acquired acute Chagas disease (CD). METHODS: A case-control, cohort-nested, epidemiological study was conducted during an outbreak of acute CD that affected a school community. Structured interviews were designed to identify symptoms and sources of infection. Electrocardiograms were obtained for all patients. Specific serum antibodies were assessed by immunoenzimatic and indirect hemagglutination tests. In some cases, parasitemia was tested directly or by culture, animal inoculation, and/or a polymerase chain reaction technique. RESULTS: Infection was confirmed in 103 of 1000 exposed individuals. Of those infected, 75% were symptomatic, 20.3% required hospitalization, 59% showed ECG abnormalities, parasitemia was documented in 44, and 1 child died. Clinical features differed from those seen in vectorial transmission. The infection rate was significantly higher among younger children. An epidemiological investigation incriminated contaminated fresh guava juice as the sole source of infection. CONCLUSIONS: This outbreak was unique, because it affected a large, urban, predominantly young, middle-class, otherwise healthy population and resulted in an unprecedented public health emergency. Rapid diagnosis and treatment avoided higher lethality. Food-borne transmission of T. cruzi may occur more often than is currently recognized. PMID- 20307206 TI - Temporal expression of adhesion factors and activity of global regulators during establishment of Staphylococcus aureus nasal colonization. AB - The human pathogen Staphylococcus aureus successfully colonizes its primary reservoir, the nasal cavity, most likely by regulatory adaptation to the nose environment. Cotton rats represent an excellent model for the study of bacterial gene expression in the initial phases of colonization. To gain insight into the expression profile necessary for the establishment of colonization, we performed direct transcript analysis by quantitative real-time reverse-transcription polymerase chain reaction on cotton rat noses removed from euthanized animals on days 1, 4, or 10 after instillation of 2 human S. aureus nose isolates. Global virulence regulators (agr, sae) were not active in this early phase, but the essential 2-component regulatory system WalKR seems to play an important role. Accordingly, an elevated expression of walKR target genes (sak, sceD) could be detected. In agreement with previous studies that demonstrated the essential role played by wall teichoic acid (WTA) polymers in nasal colonization, we detected a strongly increased expression of WTA-biosynthetic genes. The expression profile switched to production of the adhesive proteins ClfB and IsdA at later stages of the colonization process. These data underscore the temporal differences in the roles of WTA and surface proteins in nasal colonization, and they provide the first evidence for a regulation of WTA biosynthesis in vivo. PMID- 20307207 TI - Orally acquired Chagas disease: lessons from an urban school outbreak. PMID- 20307209 TI - On the composition of the preimmune repertoire of T cells specific for Peptide major histocompatibility complex ligands. AB - Millions of T cells are produced in the thymus, each expressing a unique alpha/beta T cell receptor (TCR) capable of binding to a foreign peptide in the binding groove of a host major histocompatibility complex (MHC) molecule. T cell mediated immunity to infection is due to the proliferation and differentiation of rare clones in the preimmune repertoire that by chance express TCRs specific for peptide-MHC (pMHC) ligands derived from the microorganism. Here we review recent findings that have altered our understanding of how the preimmune repertoire is established. Recent structural studies indicate that a germline-encoded tendency of TCRs to bind MHC molecules contributes to the MHC bias of T cell repertoires. It has also become clear that the preimmune repertoire contains functionally heterogeneous subsets including recent thymic emigrants, mature naive phenotype cells, memory phenotype cells, and natural regulatory T cells. In addition, sensitive new detection methods have revealed that the repertoire of naive phenotype T cells consists of distinct pMHC-specific populations that consistently vary in size in different individuals. The implications of these new findings for the clonal selection theory, self-tolerance, and immunodominance are discussed. PMID- 20307208 TI - Control of immunity by the TNFR-related molecule OX40 (CD134). AB - TNFR/TNF superfamily members can control diverse aspects of immune function. Research over the past 10 years has shown that one of the most important and prominent interactions in this family is that between OX40 (CD134) and its partner OX40L (CD252). These molecules strongly regulate conventional CD4 and CD8 T cells, and more recent data are highlighting their ability to modulate NKT cell and NK cell function as well as to mediate cross-talk with professional antigen presenting cells and diverse cell types such as mast cells, smooth muscle cells, and endothelial cells. Additionally, OX40-OX40L interactions alter the differentiation and activity of regulatory T cells. Blocking OX40L has produced strong therapeutic effects in multiple animal models of autoimmune and inflammatory disease, and, in line with a prospective clinical future, reagents that stimulate OX40 signaling are showing promise as adjuvants for vaccination as well as for treatment of cancer. PMID- 20307210 TI - The role of ThPOK in control of CD4/CD8 lineage commitment. AB - During alphabeta T cell development, cells diverge into alternate CD4 helper and CD8(+) cytotoxic T cell lineages. The precise correlation between a T cell's CD8 and CD4 choice and its TCR specificity to class I or class II MHC was noted more than 20 years ago, and establishing the underlying mechanism has remained a focus of intense study since then. This review deals with three formerly discrete topics that are gradually becoming interconnected: the role of TCR signaling in lineage commitment, the regulation of expression of the CD4 and CD8 genes, and transcriptional regulation of lineage commitment. It is widely accepted that TCR signaling exerts a decisive influence on lineage choice, although the underlying mechanism remains intensely debated. Current evidence suggests that both duration and intensity of TCR signaling may control lineage choice, as proposed by the kinetic signaling and quantitative instructive models, respectively. Alternate expression of the CD4 and CD8 genes is the most visible manifestation of lineage choice, and much progress has been made in defining the responsible cis elements and transcription factors. Finally, important clues to the molecular basis of lineage commitment have been provided by the recent identification of the transcription factor ThPOK as a key regulator of lineage choice. ThPOK is selectively expressed in class II-restricted cells at the CD4(+)8(lo) stage and is necessary and sufficient for development to the CD4 lineage. Given the central role of ThPOK in lineage commitment, understanding its upstream regulation and downstream gene targets is expected to reveal further important aspects of the molecular machinery underlying lineage commitment. PMID- 20307211 TI - The sterile inflammatory response. AB - The acute inflammatory response is a double-edged sword. On the one hand, it plays a key role in initial host defense, particularly against many infections. On the other hand, its aim is imprecise, and as a consequence, when it is drawn into battle, it can cause collateral damage in tissues. In situations where the inciting stimulus is sterile, the cost-benefit ratio may be high; because of this, sterile inflammation underlies the pathogenesis of a number of diseases. Although there have been major advances in our understanding of how microbes trigger inflammation, much less has been learned about this process in sterile situations. This review focuses on a subset of the many sterile stimuli that can induce inflammation-specifically dead cells and a variety of irritant particles, including crystals, minerals, and protein aggregates. Although this subset of stimuli is structurally very diverse and might appear to be unrelated, there is accumulating evidence that the innate immune system may recognize them in similar ways and stimulate the sterile inflammatory response via common pathways. Here we review established and emerging data about these responses. PMID- 20307212 TI - Slow down and survive: Enigmatic immunoregulation by BTLA and HVEM. AB - B and T lymphocyte associated (BTLA) is an Ig domain superfamily protein with cytoplasmic immunoreceptor tyrosine-based inhibitory motifs. Its ligand, herpesvirus entry mediator (HVEM), is a tumor necrosis factor receptor superfamily member. The unique interaction between BTLA and HVEM allows for a system of bidirectional signaling that must be appropriately regulated to balance the outcome of the immune response. HVEM engagement of BTLA produces inhibitory signals through SH2 domain-containing protein tyrosine phosphatase 1 (Shp-1) and Shp-2 association, whereas BTLA engagement of HVEM produces proinflammatory signals via activation of NF-kappaB. The BTLA-HVEM interaction is intriguing and quite complex given that HVEM has four other ligands that also influence immune responses, the conventional TNF ligand LIGHT and lymphotoxin alpha, as well as herpes simplex virus glycoprotein D and the glycosylphosphatidylinositol-linked Ig domain protein CD160. BTLA-HVEM interactions have been shown to regulate responses in several pathogen and autoimmune settings, but our understanding of this complex system of interactions is certainly incomplete. Recent findings of spontaneous inflammation in BTLA-deficient mice may provide an important clue. PMID- 20307214 TI - A randomized, placebo-controlled clinical trial of tacrolimus ophthalmic suspension 0.1% in severe allergic conjunctivitis. AB - AIMS: To examine the efficacy of tacrolimus ophthalmic suspension 0.1% in treating severe allergic conjunctivitis. METHODS: This was a multicenter, randomized, double-masked, placebo-controlled clinical trial. Fifty-six patients with severe allergic conjunctivitis in whom topical antiallergic agents and corticosteroids had been ineffective were randomized to tacrolimus or placebo treatment. Patients were treated either with tacrolimus or placebo twice-daily for 4 weeks. Severity of objective signs in palpebral and bulbar conjunctiva, limbus, and corneal involvement was assessed using 4 grades. Seven subjective symptoms were evaluated by visual analog scale (VAS) assessment. The primary efficacy endpoint was change in the total score of objective signs at the end of treatment. The secondary efficacy endpoints included change in the score for each objective sign and change in the VAS for each subjective symptom. Safety was assessed based on the severity and the incidence of adverse events. RESULTS: Mean change from baseline in total score for objective signs was significantly greater in the tacrolimus (-5.6 + or - 5.1) than in the placebo group (-0.1 + or - 4.5; P < 0.001). Tacrolimus significantly improved giant papillae (P = 0.001) and corneal involvement (P = 0.005). Five subjective symptoms (itching, discharge, hyperemia, lacrimation, and foreign body sensation) were significantly better in the tacrolimus than in the placebo group. The most frequent treatment-related adverse event in the tacrolimus group was mild ocular irritation upon topical instillation, which was well-tolerated. CONCLUSION: Tacrolimus ophthalmic suspension 0.1% is effective in treating severe allergic conjunctivitis. PMID- 20307215 TI - Intravitreal bevacizumab versus triamcinolone acetonide for refractory uveitic cystoid macular edema: a randomized pilot study. AB - PURPOSE: To compare intravitreal bevacizumab (IVB) versus intravitreal triamcinolone acetonide (IVT) for treatment of refractory uveitic cystoid macular edema (CME). METHODS: In this randomized clinical trial, 31 eyes with uveitic CME were allocated into the IVB group-eyes that received 1-3 injections of 1.25 mg bevacizumab (15 eyes) and the IVT group-eyes that received 1-3 injections of 2 mg triamcinolone (16 eyes). Primary outcome measure was change in best-corrected visual acuity (VA) at 36 weeks. RESULTS: Visual acuity improvement compared with baseline values was meaningful in the IVB group at 12, 24, and 36 weeks (-0.35 + or - 0.45 logMAR [P = 0.016]) and in the IVT group at 24 and 36 weeks (-0.32 + or - 0.32 logMAR [P = 0.001]). A significant central macular thickness (CMT) reduction was observed only in the IVT group at week 36 (74.6 + or - 108.0 microm [P = 0.049]). Between-group analysis disclosed no significant difference in any outcome measure. By statistically removing the factor of cataract, the IVT group had more improvement in VA (P = 0.007). CONCLUSIONS: IVB was as effective as IVT in refractory uveitic CME regarding VA improvement up to 36 weeks. Irrespective of triamcinolone-induced cataract, a more beneficial effect of IVT may be attainable. PMID- 20307216 TI - Aqueous humor concentrations of bimatoprost free acid, bimatoprost and travoprost free acid in cataract surgical patients administered multiple topical ocular doses of LUMIGAN or TRAVATAN. AB - PURPOSE: To quantify the aqueous humor (AH) concentrations of bimatoprost (amide), travoprost (isopropyl ester), and their hydrolysis products, bimatoprost free acid (BFA) and travoprost free acid (TFA), after multiple topical ocular doses of LUMIGAN and TRAVATAN, respectively, in patients awaiting cataract surgery. METHODS: In 2 separate open-label, sparse-sampling trials, glaucoma patients with cataracts received LUMIGAN (bimatoprost ophthalmic solution, 0.03%) or TRAVATAN (travoprost ophthalmic solution, 0.004%) bilaterally once daily for at least 21 days prior to cataract surgery. Anterior chamber paracentesis was performed at selected times up to 5 h after the last dose and an AH sample was collected. AH samples were assayed by an independent bioanalytical laboratory using a sensitive and validated tandem LC-MS/MS method. The assay lower limits of quantitation were 0.59 nM for bimatoprost, 0.29 nM for BFA, and 0.44 nM for TFA. RESULTS: AH concentrations of BFA (17-phenyl-trinor PGF(2alpha)) were quantifiable in all but one sample at 0.5 h. The maximum concentration achieved (C(max)) of BFA was 30.9 + or - 16.41 nM (n =5), observed at 2 h postdose. AH concentrations of bimatoprost amide were lower than BFA at all time points, with a C(max) of 6.81 + or - 1.36 nM (n = 7) at 1 h postdose. For TFA, measurable AH concentrations were obtained at all time points with a TFA C(max) of 3.91 + or - 2.27 nM (n = 5), which was observed at 3 h after the dose (all data are mean + or - SEM). CONCLUSIONS: Once daily topical ocular administration of LUMIGAN or TRAVATAN for 3 weeks resulted in significant concentrations of BFA and TFA in the AH. Quantifiable levels of bimatoprost amide were also measured. Maximum concentrations of BFA (30.9 nM) and TFA (3.91 nM) in the anterior chamber are sufficient to fully activate the FP prostanoid receptors in the target cells of the ciliary muscle and trabecular meshwork. Both bimatoprost in LUMIGAN and travoprost in TRAVATAN are essentially prodrugs that are rapidly hydrolyzed to their respective free acids that induce the IOP-lowering effect observed with both drugs in vivo. PMID- 20307217 TI - Prospects of intermittent preventive treatment of adults against malaria in areas of seasonal and unstable malaria transmission, and a possible role for chloroquine. AB - Chloroquine (CQ) is outmoded as an antimalarial drug in most of the malarial world because of the high resistance rate of parasites. The parasite resistance to CQ is attributed to pfcrt/pfmdr1 gene mutations. Recent studies showed that parasites with mutations of pfcrt/pfmdr1 genes are less virulent, and that those with dhfr/dhps mutations are more susceptible to host immune clearance; the former and latter mutations are linked. In the era of artemisinin-based combination therapy, the frequency of pfcrt/pfmdr1 wild variants is expected to rise. In areas of unstable malaria transmission, the unpredictable severe epidemics of malaria and epidemics of severe malaria could result in high mortality rate among the semi-immune population. With this in mind, the use of CQ for intermittent preventive treatment of adults (IPTa) is suggested as a feasible control measure to reduce malaria mortality in adults and older children without reducing uncomplicated malaria morbidity. The above is discussed in a multidisciplinary approach validating the deployment of molecular techniques in malaria control and showing a possible role for CQ as a rescue drug after being abandoned. PMID- 20307213 TI - Molecular basis of calcium signaling in lymphocytes: STIM and ORAI. AB - Ca(2+) entry into cells of the peripheral immune system occurs through highly Ca(2+)-selective channels known as CRAC (calcium release-activated calcium) channels. CRAC channels are a very well-characterized example of store-operated Ca(2+) channels, so designated because they open when the endoplasmic reticulum (ER) Ca(2+) store becomes depleted. Physiologically, Ca(2+) is released from the ER lumen into the cytoplasm when activated receptors couple to phospholipase C and trigger production of the second messenger inositol 1,4,5-trisphosphate (IP(3)). IP(3) binds to IP(3) receptors in the ER membrane and activates Ca(2+) release. The proteins STIM and ORAI were discovered through limited and genome wide RNAi screens, respectively, performed in Drosophila cells and focused on identifying modulators of store-operated Ca(2+) entry. STIM1 and STIM2 sense the depletion of ER Ca(2+) stores, whereas ORAI1 is a pore subunit of the CRAC channel. In this review, we discuss selected aspects of Ca(2+) signaling in cells of the immune system, focusing on the roles of STIM and ORAI proteins in store operated Ca(2+) entry. PMID- 20307218 TI - The role of antibacterial therapy in atopic eczema. AB - IMPORTANCE OF THE FIELD: Atopic eczema is highly colonized with Staphylococcus aureus in lesional as in non-lesional skin. Antimicrobial therapy as part of a comprehensive therapeutic concept in atopic eczema has been discussed for a long a time. AREAS COVERED IN THIS REVIEW: A complete literature review of the accessible publications concerning antibacterial and antiseptic therapy has been undertaken. WHAT THE READER WILL GAIN: This review covers the literature on antimicrobial therapy in atopic eczema and will try to weigh the different publications in the field. TAKE-HOME MESSAGE: A beneficial role for antibacterial/antiseptic therapy on top of anti-inflammatory therapy in atopic eczema has to be questioned. However, a role in prevention of overt skin infection seems possible. PMID- 20307219 TI - Castrate-resistant prostate cancer: therapeutic strategies. AB - IMPORTANCE OF THE FIELD: Castrate-resistant prostate cancer continues to be inadequately addressed by currently available therapies. AREAS COVERED IN THIS REVIEW: This review will discuss recent developments, including new chemotherapies and chemotherapy regimens, antiangiogenic therapy, immunotherapy, and other new agents, such as endothelin-A receptor antagonists and clusterin inhibitors. WHAT THE READER WILL GAIN: The reader will gain an understanding of the therapies in development for castration-resistant disease. TAKE HOME MESSAGE: Therapies focused on multiple different targets are currently being studied for castrate-resistant prostate cancer. PMID- 20307221 TI - Olopatadine: a drug for allergic conjunctivitis targeting the mast cell. AB - IMPORTANCE OF THE FIELD: Ocular allergic diseases are characterized by specific activation of conjunctival mast cells with subsequent release of preformed and newly formed mediators. Mast cells are thus the first therapeutic target of ocular anti-allergic treatments. AREAS COVERED IN THIS REVIEW: In this review, a Medline literature search was conducted on conjunctival mast cells, their role in ocular allergy and mast cell stabilization by ocular anti-allergic compounds. WHAT THE READER WILL GAIN: Olopatadine hydrochloride, a mast cell stabilizer and histamine receptor antagonist, has been shown to inhibit mast cell activation in an in vitro model of human mast cell culture, reducing histamine and TNF-alpha release and upregulating proinflammatory mediators in conjunctival epithelial cells. In the in vivo conjunctival allergen challenge (CAC) model in allergic subjects, combined with objective evaluations of tear mediators and cytology, olopatadine reduced histamine tear levels and all aspects of allergic inflammation, confirming the positive clinical effects observed in active allergic patients. TAKE HOME MESSAGE: Mast cells play a central role in the pathogenesis of ocular allergy. The CAC model is ideal for assessing the mast cell stabilizing effects of anti-allergic compounds. This review of clinical studies demonstrates the superiority of olopatadine compared with other topical allergic drugs. PMID- 20307220 TI - Fixed combinations of dorzolamide-timolol and brimonidine-timolol in the management of glaucoma. AB - IMPORTANCE OF THE FIELD: The emergence of fixed-combination drugs for the treatment of glaucoma has, to some extent, changed the medical management of glaucoma. The potential benefits of these drugs include a reduction in the total number of drops and preservatives instilled per day and improved patient comfort factors, which may contribute to better compliance. Combination medications may also improve therapeutic efficacy and play an important role in controlling medication cost. However, the fixed dosing may be a disadvantage in some cases. AREA COVERED IN THIS REVIEW: This review describes the composition, pharmacokinetics, mode of action, efficacy, side effects, and safety profile of fixed-combination dorzolamide-timolol and fixed-combination brimonidine-timolol. WHAT THE READER WILL GAIN: Understanding of the pros, cons, and safety profile of two FDA approved fixed-combination antiglaucoma medication. TAKE HOME MESSAGE: Fixed-combination medications may be a reasonable adjunct to prostaglandins if a large drop in the intraocular pressure (IOP) is desired and adding only one medication is unlikely to reach the target IOP range. Both mentioned drugs are effective in reducing the IOP and further clinical studies will help identify differences in efficacy between the two. The clinician must make an individualized assessment of the medication's risk-benefit profile for each patient. PMID- 20307222 TI - Nebivolol in chronic heart failure: current evidence and future perspectives. AB - IMPORTANCE OF THE FIELD: Chronic activation of the sympathetic nervous system leads to deterioration of cardiovascular function in heart failure patients. In systolic heart failure, beta-blockers were proven to be effective in decreasing the number of deaths and improving morbidity. However, beta-blockers are a heterogeneous drug group, consisting of agents with different selectivity for adrenergic receptors and/or additional effects in heart or peripheral circulation. AREAS COVERED IN THE REVIEW: We describe the role of the sympathetic nervous system, beta-blockers and specifically nebivolol in chronic heart failure. WHAT THE READER WILL GAIN: Nebivolol is a third-generation beta-blocker, with high beta(1)/beta(2) selectivity. Moreover, it has important vasodilating properties, by stimulating the production of nitric oxide. Smaller studies have already shown beneficial effects of nebivolol treatment on surrogate end points in heart failure patients. The recently published SENIORS (Phase III) study in an elderly heart failure population demonstrated a decreased number of clinical events in patients treated with nebivolol. Importantly, this effect was observed in patients with both impaired and preserved left ventricular systolic function. TAKE HOME MESSAGE: Specific beta-blockers may have distinct effects in various subgroups of heart failure patients. So far, nebivolol is the only beta-blocker to have been shown effective in elderly heart failure patients, regardless of their left ventricular ejection fraction. PMID- 20307223 TI - Armodafinil in the treatment of excessive sleepiness. AB - IMPORTANCE OF THE FIELD: Excessive sleepiness causes impaired quality of life and increases the risk of poor health and accidents. Armodafinil is a wake-promoting agent approved in 2007 by the US Food and Drug Administration for the treatment of excessive sleepiness arising from narcolepsy, obstructive sleep apnea (OSA; even after optimal treatment for the underlying obstruction) and shift-work disorder (SWD). It is the R-enantiomer of modafinil, which is a racemic mixture of R- and S-enantiomers. AREAS COVERED IN THIS REVIEW: This review summarizes the recent primary data on the pharmacokinetics, clinical efficacy and safety of armodafinil using literature published since 2005 that was identified from PubMed. WHAT THE READER WILL GAIN: The review describes recent advances in the understanding of the pharmacokinetic profile of the drug and why this may improve wakefulness later after dosing compared with modafinil. It also describes the recent efficacy and safety data supporting the use of armodafinil to treat excessive sleepiness in indicated patients. TAKE HOME MESSAGE: Armodafinil is a useful therapy for the treatment of excessive sleepiness arising from a number of clinical conditions. It is generally well tolerated and has a low potential for abuse or tolerance. PMID- 20307224 TI - Review of palonosetron: emerging data distinguishing it as a novel 5-HT(3) receptor antagonist for chemotherapy-induced nausea and vomiting. AB - IMPORTANCE OF THE FIELD: Since the advent of the 5-hydroxytryptamine 3 receptor antagonists (5-HT3RAs) in the 1990s, dramatic improvements have been achieved in the field of antiemetic therapy. The enhanced prevention of delayed and overall chemotherapy-induced nausea and vomiting (CINV) offered by palonosetron, a second generation 5-HT3RA and aprepitant, the first neurokinin-1 receptor antagonists (NK-1RA) represent the only significant treatment advances in the past decade. While initial trials of single-dose palonosetron indicated a potential benefit over first-generation 5-HT3RAs, only recently have new data become available, increasing the weight of evidence distinguishing it as a new 5-HT3RA in the class. AREAS COVERED IN THIS REVIEW: History of antiemetics and palonosetron, including clinical trials and pharmacological research, and literature published between 1981 and 2010 are covered. WHAT THE READER WILL GAIN: Unique pharmacological characteristics of palonosetron exhibiting prolonged half-life, high receptor affinity, allosteric interactions and positive cooperativity with 5 HT3 receptor resulting in long-term alteration and internalization of this receptor may explain the clinical observation of palonosetron. TAKE HOME MESSAGE: This review of recent progress in antiemetic therapy focuses on the newest data on palonosetron and discusses future trials and implications for clinical practice, with the overall goal of learning from history. PMID- 20307225 TI - Thrombin receptor antagonism -the potential of antiplatelet medication SCH 530348. AB - IMPORTANCE OF THE FIELD: Coronary artery disease is a leading cause of morbidity and mortality worldwide. Platelet activation and subsequent thrombus formation play a central role in disease progression and development of acute coronary syndromes (ACS). Despite widespread use of single and dual antiplatelet therapies in atherothrombotic disease, ischemic complications remain common. Therefore, the need exists for new antiplatelet agents that are more effective, but with acceptable safety profiles (i.e., do not increase risk of bleeding). Antiplatelet agents available at present are effective in blocking the cyclo-oxygenase, ADP mediated and final common (IIb/IIIa receptor) pathways for platelet activation. Recently, there has been more interest in inhibition of the proteinase-activated receptor-1 (PAR-1), which blocks thrombin-mediated platelet activation. AREAS COVERED IN THIS REVIEW: This review covers the pharmacology, pharmacokinetics and development of the new PAR(1) antagonist, SCH 530348 in a review of all publications relevant to the topic over the last 10 years. Phase II clinical trials indicate that addition of this agent to current antiplatelet regimens may provide additional antithrombotic protection without an increase in bleeding. Results of the ongoing Phase III trials, examining the use of SCH 530348 in patients with ACS and for secondary prevention of ischemic events are anxiously awaited. WHAT THE READER WILL GAIN: The review is a summary of all pharmacologic properties and current clinical data available on the PAR1 antagonist SCH 530348. The readers will be introduced to its novel mechanism of action, advantages over current antiplatelet agents and potential future applications should ongoing clinical trials confirm its efficacy in reducing platelet activity. TAKE HOME MESSAGE: SCH 530348 is a new, orally administered antiplatelet agent that blocks the protease-activated thrombin receptor on the platelet. Early clinical data indicate that it is associated with a lower risk of bleeding. However, its efficacy in improving clinical outcomes in patients with coronary disease remains to be confirmed in ongoing Phase III clinical trials. PMID- 20307226 TI - Bosentan. AB - IMPORTANCE TO THE FIELD: Pulmonary arterial hypertension (PAH) is a morbid condition with high mortality if left untreated. Bosentan is an effective treatment option for group 1 pulmonary arterial hypertension. Bosentan improves exercise tolerance and functional class and delays the time to clinical worsening in these patients. Investigation is ongoing to determine its efficacy in other groups of pulmonary hypertension. AREAS COVERED IN THIS REVIEW: This review provides a background on endothelin activity in PAH, as a rationale for the use of bosentan in this disease. It also presents evidence from key clinical trials of bosentan and discusses future directions in the study of bosentan to help the clinician better understand the role of bosentan in PAH management. WHAT THE READER WILL GAIN: i) An understanding of the rationale for using endothelin receptor antagonists in treating PAH; ii) an understanding of the clinical evidence to support bosentan for the treatment of PAH; and iii) an understanding of how to use bosentan optimally in the treatment of PAH. TAKE HOME MESSAGE: Bosentan is an effective and safe treatment for patients with PAH. Patients with suspected PAH should be evaluated carefully as the use of bosentan in non-group 1 pulmonary hypertension is still being investigated. Patients on bosentan should be monitored with monthly liver transaminase testing. Coadministration with other drugs should be reviewed carefully as drug-drug interactions may be important. PMID- 20307227 TI - Insights from the dabigatran versus warfarin trial in patients with venous thromboembolism (the RE-COVER trial). AB - In this clinical trial evaluation, we revisit the RE-COVER study, a large multicenter, randomized, double-blind, noninferiority trial on patients with acute venous thromboembolism treated with dabigatran versus warfarin. Study design and key results are re-evaluated in the context of previous work and future perspectives. PMID- 20307230 TI - Genetic variability of the european corn borer, Ostrinia nubilalis, suggests gene flow between populations in the Midwestern United States. AB - The European corn borer, Ostrinia nubilalis (Hubner) (Lepidoptera: Crambidae), is a widely distributed and serious economic pest to corn production in the U.S. Genetic variability of O. nubilalis was studied in 18 sub-populations in the upper Midwestern United States using amplified fragment length polymorphism. The relatively low GST values indicate that more variation exists within populations than between populations. High gene flow (Nm) values were indicated across the entire O. nubilalis population; the lowest degree of gene flow was in the northern samples (Nm = 1.96) and the highest degree of gene flow was in the southern samples (Nm = 2.77). The differences observed in the respective regions (north vs. south) may be explained by the voltinism patterns (univoltine vs. multivoltine, respectively) of O. nubilalis: southern multivoltine populations have opportunities for multiple matings for the duration of the year, further mix alleles. AMOVA results also indicated that most of the genetic variation was within sub-populations ( approximately 81% of total variation); less variation ( approximately 13%) was detected among populations within each of the three regions as designated for this study. However, the most striking and unexpected result was the low percentage of variation between all groups ( approximately 6%), further supporting implications of a high degree of gene flow. These results provide support for current requirements of refugia corn planting in Bt-corn management. These results also indicate that if resistance to Bt were to evolve in O. nubilalis, quick action would be necessary to deter the rapid spread of the gene for resistance. PMID- 20307229 TI - Alkalinization in the isolated and perfused anterior midgut of the larval mosquito, Aedes aegypti. AB - In the present study, isolated midguts of larval Aedes aegypti L. (Diptera: Culicidae) were mounted on perfusion pipettes and bathed in high buffer mosquito saline. With low buffer perfusion saline, containing m-cresol purple, transepithelial voltage was monitored and luminal alkalinization became visible through color changes of m-cresol purple after perfusion stop. Lumen negative voltage and alkalinization depended on metabolic energy and were stimulated in the presence of serotonin (0.2 micromol l(-1)). In some experiments a pH microelectrode in the lumen recorded pH values up to 10 within minutes after perfusion stop. The V-ATPase inhibitor concanamycin (50 micromol l(-1)) on the hemolymph side almost abolished V(te) and inhibited luminal alkalinization. The carbonic anhydrase inhibitor, methazolamide (50 micromol l(-1)), on either the luminal or hemolymph-side, or the inhibitor of anion transport, DIDS (1 mmol l( 1)) on the luminal side, had no effect on V(te) or alkalinization. Cl(-) substitution in the lumen or on both sides of the tissue affected V(te), but the color change of m-cresol purple was unchanged from control conditions. Hemolymph side Na(+) substitution or addition of the Na(+)/H(+) exchange inhibitor, amiloride (200 micromol l(-1)), reduced V(te) and luminal alkalinization. Luminal amiloride (200 micromol l(-1)) was without effects on V(te) or alkalinization. High K(+) (60 mmol l(-1)) in the lumen reduced V(te) without affecting alkalinization. These results indicate that strong luminal alkalinization in isolated and perfused anterior midgut of larval A. aegypti depends on basolateral V-ATPase, but is apparently independent of carbonic anhydrase, apical Cl( )/HCO(3)(-) exchange or apical K(+)/2H(+) antiport. PMID- 20307231 TI - Phototactic responses to ultraviolet and white light in various species of Collembola, including the eyeless species, Folsomia candida. AB - Previous observations have indicated homology in the cellular components between Collembolan eyes and the compound eyes of insects. However, behavioral or physiological studies indicating similarities in function are lacking. Collembolan eyes were examined from three species in the Family Isotomidae using scanning electron microscopy. Collembolan eyes are arranged dorsally and laterally on each side of the head in two species, Proisotoma minuta with eight eyes on each side of the head and Folsomia similis with one eye on each side of the head. In both of these species the eyes were located just posterior to the postantennal organ. In Folsomia candida, no external eye structures were detected. These three species were assayed for a series of behavioral preferences using ultraviolet (UV), white light and dark, and temperature conditions. The tests demonstrated that over 76% of all three species, including the eyeless F. Candida, chose white over UV light, over 69% preferred dark over UV, and over 77% favored dark over white light. The results demonstrated that all three species detect both UV and white light and avoid it, preferring cool, dark habitats. From the results of this study, it is hypothesized that F. candida may, in fact, be only "lensless" and may be able to detect light by having internal, non-ocular photoreceptors. Further histological studies are needed to investigate this possibility. PMID- 20307232 TI - A new nucleolar body appears in Drosophila saltans salivary gland cells before histolysis, in programmed cell death. AB - The salivary glands of Drosophila saltans (saltans group, saltans subgroup) analyzed in an advanced stage of programmed cell death showed the appearance of a single, round, nucleolar corpuscle inside the highly altered nucleus of every gland cell, at a time during which the integrity of the original nucleolus was already lost and the original nucleolar material apparently disappeared. In the same nuclei, which already had also lost the characteristic chromosome structure, some delicate chromosome threads were maintained. In many cells, the new nucleolar corpuscle and these chromosome threads are associated. These findings are novel. However, the hypothesis put forward concerning their meaning remains dependent on other studies. PMID- 20307233 TI - Impact of the stem borer, Dectes texanus, on yield of the cultivated sunflower, Helianthus annuus. AB - Foliar and soil-drench insecticide treatments were used in attempts to manipulate infestation of cultivated sunflower plants, Helianthus annuus LeConte (Asterales: Asteraceae) by Dectes texanus LeConte, (Coleoptera: Cerambycidae) a serious pest of sunflowers in the High Plains of the USA. Seed yields were assessed on a per plant basis for both oilseed and confection type sunflower hybrids in two years. Both insecticide treatments (foliar e-cyhalothrin and soil-drench carbofuran) improved yield of oilseed sunflowers in 2004, but not in 2005. Yield of confection hybrids was improved by a systemic fungicide (thiophanate methyl) in 2005, but insecticides did not improve yield in either year. Both insecticide treatments gave good control of various stalk-boring insects such as Cylindrocopturus adspersus (Coleoptera: Curculionidae), Mordellistena sp. (Coleoptera: Mordellidae), and Pelochrista womanana (Lepidoptera: Tortricidae), but neither gave better than 50% control of D. texanus. Plants were sorted according to the presence or absence of D. texanus larvae and no reduction was found in total seed weight, seed size, or oil content as a result of infestation. However, mature larvae of D. texanus girdle stalks at the base in preparation for overwintering, a behavior that reduced stalk breakage force by 34-40%, leading to yield losses through lodging. At harvest in 2005, there were differences between cultivars and among treatments in the proportions of D. texanus larvae that had girdled their plants at harvest. It was concluded that further research aimed at reducing crop losses to D. texanus should focus on means of delaying stalk desiccation and/or deterioration, factors that appear to trigger girdling behavior. PMID- 20307234 TI - Tissue and life stage specificity of glutathione S-transferase expression in the Hessian fly, Mayetiola destructor: implications for resistance to host allelochemicals. AB - Two new Delta and Sigma glutathione S-transferases (GSTs) in the Hessian fly, Mayetiola destructor (Diptera: Cecidomyiidae), were characterized and transcription profiles described. The deduced amino acid sequences for the two M. destructor Delta GSTs (MdesGST-1 and MdesGST-3) showed high similarity with other insect Delta GSTs including the conserved catalytic serine residue. The deduced amino acid sequence for the M. destructor Sigma GST (MdesGST-2) showed high similarity with other insect Sigma GSTs including the conserved glutathione and substrate binding sites. Quantitative tissue expression analysis showed that mRNA levels for MdesGST-1 were predominant in fat body, whereas for MdesGST-2 and MdesGST-3 expression was predominant in the midgut. Temporal expression during development showed peak mRNA levels for MdesGST-1 during larval development, but in the pupal stage for MdesGST-2. MdesGST-3 showed a constitutive expression pattern throughout development. M. destructor feeds on wheat, and expression analysis after feeding indicated that mRNA levels for MdesGST-1 were significantly higher in incompatible interactions in which larvae fed on resistant wheat, while MdesGST-3 was significantly higher in compatible interactions when larvae fed on susceptible wheat. MdesGST-2 showed an equivalent expression pattern during both interactions. These results suggest that the M. destructor Delta GSTs are important in detoxifying wheat allelochemicals during feeding, while Sigma GST participates in metabolism of endogenous substrates. PMID- 20307235 TI - Comparative studies of the influence of relative humidity and temperature on the longevity and fecundity of the parasitoid, Cotesia flavipes. AB - The parasitoid, Cotesia flavipes (Cameron) (Hymenoptera: Braconidae), was introduced for biological control of the stemborer, Chilo partellus (Swinhoe) (Lepidoptera: Crambidae), in eastern and southern African countries. The parasitoid became firmly established in Ethiopia, with varying density and distribution in various regions of the country indicating that there are factors regulating the success of the parasitoid. From previous studies, it was known that the population of the parasitoid released, the type of host, and temperature highly affect some of the biological parameters of the parasitoid. The current studies were undertaken to understand the individual and interactive effect of temperature and relative humidity on the longevity and fecundity of C. flavipes. The study was conducted on C. flavipes collected from the Melkassa Agricultural Research Center Experimental Field, Ethiopia. C. flavipes was reared in the laboratory on C. partellus feeding on pieces of sorghum stem. The longevity experiment was conducted at 10, 20, 30 and 40 degrees C, while the fecundity experiment was conducted at 20, 25, 28 and 30 degrees C. For both experiments 40 50%, 60-70% and 80-90% relative humidity regimes were used. The results obtained indicate that the interactive effect of temperature and relative humidity significantly affected the longevity, the number of oocytes, and fecundity of C. flavipes implying that the two factors play an important role in the success of the parasitoid as a biocontrol agent against C. partellus. The results obtained suggests the importance of the selection of target release sites for maximum efficiency of the parasitoid, which can have a positive impact on the on-going augmentative release of C. flavipes in Ethiopia. PMID- 20307236 TI - Characterization of microsatellite loci in the western subterranean termite, Reticulitermes hesperus, and cross-amplification in closely related cryptic species. AB - New, and previously reported microsatellites, were characterized for a group of four cryptic sibling species in California (USA) in the subterranean termite genus Reticulitermes with the goal of finding loci appropriate for population and species level studies. Three new microsatellites were identified originating from R. hesperus, and 19 loci previously characterized in R. flavipes and R. santonensis were examined. Of the three loci specifically developed for R. hesperus, none amplify with the other species. Variation appropriate for population level studies was found in 4-13 loci depending on the species. Fifteen loci appeared to be appropriate for use at the species level. Unique or monomorphic alleles are found among the four species, indicating these loci will be taxonomically informative for this group. PMID- 20307237 TI - Identification of termite species and subspecies of the genus Zootermopsis using near-infrared reflectance spectroscopy. AB - Dampwood termites of the genus Zootermopsis (Isoptera: Termopsidae) are an abundant group of basal termites found in temperate forests of western North America. Three species are currently recognized in the genus and one of these species is subdivided into two subspecies. Although morphological and genetic characters are useful in differentiating among the three species and the two subspecies, respectively, only hydrocarbon analysis can enable differentiation both among the three species and the two subspecies. Due to the limitations of hydrocarbon analysis, such as the need for fresh specimens, alternative methods that could rapidly and accurately identify Zootermopsis would be useful. Using a partial least squares analysis of near-infrared spectra, each of the Zootermopsis species and subspecies were identified with greater than 95% and 80% accuracy, respectively. Neural network analysis of the near-infrared spectra successfully enabled the identification of the species and subspecies with greater than 99% accuracy. The inexpensive, reproducible, and rapid nature of near-infrared spectroscopy makes it a viable alternative to morphological, hydrocarbon, or genetic analysis for identifying Zootermopsis. PMID- 20307238 TI - Coccinellids, aphids, and pollen in diversified vegetable fields with transgenic and isoline cultivars. AB - The influence of concurrent introduction of three transgenic vegetable cultivars on seasonal dynamics of coccinellids and their food, aphids and pollen, was examined within diversified farm systems practicing insect pest management in northeastern US agroecosystems. The transgenic cultivars used included sweet corn, potato, and winter squash, expressing Cry1(A)b, Cry3A, and plant viral coat proteins that target Lepidoptera, Coleoptera, and aphid-transmitted viruses, respectively. Transgenic systems reduced insecticides by 25%. Weekly differences in coccinellid density between transgenic and isoline crops were rare and transitory, governed by timing of at-planting or foliar insecticide use patterns; however cumulative frequencies for three of the six coccinellid species differed between transgenic and isoline crops. At a multicrop, farm systems level, seasonal dynamics of the coccinellids and aphids tracked dynamics in the sweet corn, which far surpassed the other crops in abundance of coccinellids and pollen, and harbored consistently higher aphid densities. Although these results warrant further study, the patterns suggest that diversified transgenic vegetable crops under current commercial management demonstrated transitory conservation of coccinellids, and that integration with selective insecticides or other IPM tactics could increase this potential. PMID- 20307240 TI - Impact of release rates on the effectiveness of augmentative biological control agents. AB - To access the effect of augmentative biological control agents, 31 articles were reviewed that investigated the impact of release rates of 35 augmentative biological control agents on the control of 42 arthropod pests. In 64% of the cases, the release rate of the biological control agent did not significantly affect the density or mortality of the pest insect. Results where similar when parasitoids or predators were utilized as the natural enemy. Within any order of natural enemy, there were more cases where release rates did not affect augmentative biological control than cases where release rates were significant. There were more cases in which release rates did not affect augmentative biological control when pests were from the orders Hemiptera, Acari, or Diptera, but not with pests from the order Lepidoptera. In most cases, there was an optimal release rate that produced effective control of a pest species. This was especially true when predators were used as a biological control agent. Increasing the release rate above the optimal rate did not improve control of the pest and thus would be economically detrimental. Lower release rates were of ten optimal when biological control was used in conjunction with insecticides. In many cases, the timing and method of biological control applications were more significant factors impacting the effectiveness of biological control than the release rate. Additional factors that may limit the relative impact of release rates include natural enemy fecundity, establishment rates, prey availability, dispersal, and cannibalism. PMID- 20307241 TI - Fungistatic activity of freshly killed termite, Nasutitermes acajutlae, soldiers in the Caribbean. AB - Termites may have high exposure to both pathogenic and competitive fungal species. Previous studies have shown anti-fungal properties of the primary components (alpha-pinene and limonene) of Nasutitermes frontal glands that are present on soldiers. In this study, the termite Nasutitermes acajutlae (Isoptera: Termitidae) was used to examine if the growth of naturally occurring fungi was inhibited by soldiers, as compared to workers that do not have frontal glands. Soldiers and workers were killed, surface sterilized, and placed on nutrient agar either singly or in combinations with other termites. Time until appearance of fungus and growth of visible fungal colonies was determined. Fungus appeared significantly earlier in cultures with single workers than with single soldiers (P < 0.001). Once fungus appeared, there were no significant differences in growth rate. When worker and/or soldier fluids were combined in one culture, fungal growth appeared later in cultures containing soldiers; growth was significantly slower in colonies with 5 workers and 5 soldiers than in cultures with 5 workers alone; P < 0.001. Finally, growth appeared later in cultures with 5 soldiers than in cultures with one soldier, suggesting a dose-response. Fungi that grew from termites were mostly non-pathogenic, suggesting the anti-fungal properties of soldiers may inhibit both pathogens and competitors. PMID- 20307242 TI - Cyclin B is an immunohistochemical proliferation marker which can predict for breast cancer death in low-risk node negative breast cancer. AB - Patients with low-risk node negative breast cancer have an excellent prognosis with 5% breast cancer mortality at 10 years. However, prognostic factors are needed to identify poor prognostic patients who might benefit from adjuvant systemic therapy. Proliferation has been identified as the most important component of gene expression profiles. Cyclin B is a proliferative marker easily assessed by immunohistochemistry. We wanted to examine cyclin B as a prognostic factor in low-risk breast cancer patients. PATIENTS AND METHODS: Using an experimental study design, we compared women dying early from their breast cancer (n=17) with women free from relapse more than eight years after initial diagnosis (n=24). All women had stage I, node negative and hormone receptor positive disease. None had received adjuvant chemotherapy. Tumor samples were immunostained for cyclin B using commercial antibodies. RESULTS: The mean percentage of cyclin B (12%) was significantly higher (p=0.001) in women dying from their breast cancer compared with women free from relapse (5%). High cyclin B (> or =9%) identified 11/17 patients dying from breast cancer and low cyclin B identified 22/24 patients free from relapse. The sensitivity and specificity of cyclin B was 65% and 92%, respectively. DISCUSSION: We found that low-risk node negative patients with high expression of cylin B had a significantly worse outcome than patients with low expression of cyclin B. Cyclin B could separate patients with poor survival from those with good survival with 80% accuracy. We suggest that cyclin B might be a potent prognostic factor in this low-risk patient group. PMID- 20307243 TI - Trends in the survival of patients diagnosed with cancer in female genital organs in the Nordic countries 1964-2003 followed up to the end of 2006. AB - Cancers of the female genital organs constitute more than 12% of all female cancers in the Nordic countries. The group includes cervix uteri, corpus uteri, ovary and other female genital organs including vulva and vagina, and in this study we compare the development in the Nordic countries regarding incidence, mortality and relative survival. MATERIAL AND METHODS: Data were retrieved from the NORDCAN database for the period 1964 to 2003, grouped into eight 5-year periods. The patients were followed up until the end of 2006. Analyses comprised trends in 5-year relative survival, excess mortality and age-specific relative survival. RESULTS: A substantial reduction of cervical cancer incidence followed the introduction of population-based screening in the 1970s and was also accompanied by a modest improvement in survival. Incidence trends in cancer of corpus uteri varied between the countries but the survival increased by around 20 percentage points during the study period in all countries. Ovarian cancer patients have the lowest survival among female genital cancers, but survival increased 10-15 percentage points over the 40 years of observation, while the incidence and mortality were rather stable throughout the observed period. Cancers of the other female genital organs, including vulva and vagina, are rare diagnoses and only small changes in incidence, mortality and survival have been observed over time. CONCLUSION: The declining trends in cervical cancer incidence and mortality, and improving survival of corpus uteri cancer patients, are in contrast with the rather poor prognosis associated with an ovarian cancer diagnosis. Cancer-specific differences between countries in the survival of female patients diagnosed with cancers of the cervix uteri, corpus uteri and other female genital organs are small. PMID- 20307244 TI - Fatal myocardial infarction during nilotinib treatment in a 60-year-old male patient. PMID- 20307245 TI - Mismatch repair protein expression is an independent prognostic factor in sporadic colorectal cancer. AB - Abstract Background. Mismatch repair (MMR) status has been reported as a prognostic and predictive factor in sporadic colorectal cancer (CRC). The purpose of this study was to determine the prognostic and predictive value of MMR protein expression in the adjuvant setting. Patients and methods. The MMR status in the primary tumor was retrospectively assessed on paraffin-embedded formalin-fixed samples from 1 006 patients with sporadic CRC (488 stage II and 518 stage III) using immunohistochemical analysis (IHC) of MLH1 and MSH2 expression. The patients were included in adjuvant Nordic trials between 1991 and 1996 randomly assigned to surgery alone or surgery plus adjuvant 5-fluorouracil (5-FU)-based chemotherapy. Data was censored at 120 months after surgery. Results. One hundred fifty-seven patients (15.6%) showed a loss of MMR protein expression (139 MLH1 negative, 15 MSH2 negative and 3 MLH1 and MSH2 negative) and were classified as MMR protein negative. A normal MMR protein expression was found in 849 patients who were defined as MMR protein positive. MMR protein expression was a significant prognostic marker in the entire study group with a better overall survival (OS) among patients with MMR protein negative tumors compared to patients with MMR protein positive tumors (p=0.01). In a multivariate analysis the MMR protein expression was significantly associated with OS, (HR 0.70 [95% CI, 0.40 to 0.99]; p=0.01). The MMR status did not predict survival benefit from adjuvant 5-FU-based chemotherapy. Conclusion. This study reveals that IHC of MLH1 and MSH2 expression can yield important prognostic information but is not a predictive factor for adjuvant 5-FU-based chemotherapy in sporadic CRC. PMID- 20307246 TI - Flat-detector computed tomography with intravenous contrast material application in experimental aneurysms: comparison with multislice CT and conventional angiography. AB - BACKGROUND: Despite limited soft tissue resolution flat-detector computed tomography (FD-CT) provides substantial superior spatial resolution in comparison with multislice computed tomography (MS-CT). This may add value in the visualization of small vascular structures if intravenous contrast application leads to substantial opacification and visibility of intracranial vessels or aneurysms. PURPOSE: To evaluate the feasibility of visualization of vascular structures by FD-CT angiography (FD-CTA) after intravenous contrast injection compared with MS-CTA and intra-arterial digital subtracted angiography (IADSA) in an animal model. MATERIAL AND METHODS: Aneurysms were created in the right common carotid artery in six New Zealand White Rabbits using the elastase technique. Imaging was performed using FD-CTA, MS-CTA (injection of 1 ml/kg body weight) and IADSA. Anonymized volume rendering reconstruction (VRT), maximum intensity projection (MIP), and multiplanar reconstruction (MPR) images were reconstructed and evaluated by two experienced reviewers for aneurysm geometry and vascular structure anatomy using standard tools of a dedicated workstation. RESULTS: Aneurysms could be successfully created in all animals. Measurements of aneurysm geometry (aneurysm height, width, neck width) and vascular structures (brachiocephalic trunk, carotid artery diameter and plane) were nearly identical in all three modalities. Intra- and inter-observer correlations of the different parameters showed high r values between 0.83 and 0.99. CONCLUSION: Our results show the feasibility of FD-CTA in comparison with MS-CTA and IADSA in an animal model. Despite limited soft tissue resolution, opacification of vascular structures with sufficient contrast to the surrounding structures was possible in all animals. Vascular structures appeared better delineated in FD-CTA than in MS CTA, probably due to the superior spatial resolution. PMID- 20307247 TI - Cerebral glucose metabolism: Influence on perihematomal edema formation after intracerebral hemorrhage in cat models. AB - BACKGROUND: Most intracerebral hemorrhage (ICH) imaging studies focus on structural brain changes. Stereotactic neuroimaging techniques such as magnetic resonance imaging (MRI) and positron emission tomography/computed tomography (PET/CT) are helpful in the diagnosis of ICH, monitoring the subsequent recovery and investigating its functional mechanisms. PURPOSE: To explore the influence of the changes in cerebral glucose metabolism on perihematomal edema formation in an experimental cat model of ICH. MATERIAL AND METHODS: Forty-eight cats were divided into 1 sham operation group (6 cats) and 7 ICH model groups (42 cats)". The ICH model groups were injected with 1.0 ml autologous nonheparinized blood into their thalami using accurate stereotactic guidance apparatus. MRI and (18)F fluorodeoxyglucose (FDG) PET/CT scans were acquired at 2, 6, 12, 24, 48, 72, and 120 h following the intervention. Pearson's correlation test was used to evaluate the association between T2-weighted signal intensity and the edema volume. Student's t test and q test were used to identify the times of significant temporal changes. RESULTS: The volume of perilesional edema did not significantly increase from 2 h to 12 h after ICH, but then increased by 229.4% at 24 h, peaked (by 273.5%), and steadily decreased by 72 h. The FDG intensity in perihematomal edema tissues was markedly reduced 2 h after ICH on PET images, reached its lowest level at 12 h, and then steadily increased at 24 h and 48 h. The changes of standard absorption value (SUV) in perihematomal edema were consistent with those of FDG intensity. CONCLUSION: Perihematomal glucose metabolism abnormalities have a close relationship with the formation of vasogenic edema. Furthermore, abnormal glucose metabolism may impair capillary integrity and increase blood-brain barrier permeability. PMID- 20307248 TI - Differences in uptake, localization, and processing of PNAs modified by COX VIII pre-sequence peptide and by triphenylphoshonium cation into mitochondria of tumor cells. AB - Two approaches to target PNAs (peptide nucleic acids) into mitochondria of HeLa cells were compared. In the first, PNA was modified with the lipophilic cation TPP. TPP-PNA accumulated rapidly within mitochondria driven by the membrane potential. It was found to be associated mainly with the mitochondrial membranes. In the second approach the COX VIII pre-sequence peptide was added to the PNA resulting in slow uptake of the peptide-PNA into the mitochondrial matrix. Whereas the amount of the uptake was lower, peptide-PNA was processed intramitochondrially in contrast to the TPP-PNA. Using the Chariot system to cross the cell membrane of HeLa cells, the uptake of peptide-PNA into the mitochondria was demonstrated. If a matrix localization of the free PNA is a pre requisite for the PNA interaction with mitochondrial DNA, the coupling PNA with an appropriate peptide seems to be the better strategy. PMID- 20307249 TI - IL-16 effects on A549 lung epithelial cells: dependence on CD9 as an IL-16 receptor? AB - Interleukin-16 (IL-16) is a pro-inflammatory cytokine released by many types of cells found in the lungs, including normal airway and alveolar epithelial cells. Though a chemotactin for CD4(+) cells and eosinophils, IL-16 also modulates their production of factors that influence inflammatory lung diseases, e.g., asthma and allergic rhinitis. To date, little is known about any potential autocrine-like regulatory effects of IL-16. Using a model human alveolar basal epithelial A549 cell line, the present study sought to assess lung epithelial cell responses to IL-16. Potential induced effects on cell growth/function were assessed using MTT reduction, lactate dehydrogenase release, and 5-bromo-2-deoxyuridine incorporation assays. As IL-16 (at locally high levels) can induce CD4(+) cell death via apoptosis, this potential outcome among the A549 cells was also evaluated using TUNEL and changes in expression of caspase-3 and the pro apoptotic and anti-apoptotic proteins of Bcl-2 family. The data here indicated that IL-16 inhibited A549 cell growth/function and this was associated with a marked increase in apoptosis characterized by DNA fragmentation, activation of caspase-3, and altered pro-apoptotic protein expression. Since lung epithelial cells lack the CD4 that may bind IL-16, it has been suggested that CD9 may act as an alternate receptor for this cytokine (i.e., an IL-16R). Thus, these studies also sought to determine the extent of CD9 expression on A549 cells and if any/all observed IL-16-induced changes were mediated by CD9. Flow cytometric analyses revealed the cells to be CD9(+)CD4(-). However, neutralization of the purported IL-16R with anti-CD9 antibody could not block the cytotoxic/growth inhibiting effects of IL-16. The only exception appeared to be a mitigation of a chemotactic effect of IL-16; however, studies with an equal amount of non specific antibody (of same isotype as the anti-CD9) revealed this effect to be artefactual. The neutralization study results thus suggest to us that as-yet undefined pathway(s) exist through which IL-16 may act to exert growth inhibiting/apoptosis-inducing effects on A549 cells, a cell line routinely used as a model for lung epithelial cells. PMID- 20307250 TI - Novel sustained-release fast-disintegrating multi-unit compressed tablets of lornoxicam containing Eudragit RS coated chitosan-alginate beads. AB - Novel fast-disintegrating multi-unit tablets (FDMUTs) were prepared to modify the release of lornoxicam (a potent non-steroidal anti-inflammatory drug with a short half-life) as well as to combine the advantages of multi-unit systems with the cost-effectiveness of compressed tablets. The proposed FDMUTs consisted of sustained-release lornoxicam beads directly compressed with fast-disintegrating component, containing amorphous solid dispersion of lornoxicam, anticipating rapid drug release that starts in the stomach to rapidly alleviate the painful symptoms and continues in the intestine to maintain extended analgesic effect. Initially, calcium-alginate and chitosan-alginate beads containing lornoxicam were prepared. Then, the erosion of selected beads formulation was suppressed by treatment with Eudragit RS either through polymer-reinforcement or beads coating. The beads, which elicited appropriate sustainment of lornoxicam release, were directly compressed with fast-disintegrating components to form FDMUTs. The release characteristics of the original beads were maintained after compression which indicates that the adopted compression process did not induce mechanical damage to the beads or coating. All of the prepared FDMUTs demonstrated acceptable physical properties that complied with compendial requirements. Release studies, performed in simulated gastric and intestinal fluids used in sequence to mimic the gastrointestinal transit, illustrate that the FDMUTs containing 8?mg lornoxicam equally distributed between the sustained-release beads and the fast-release component, showed the desired release profile. PMID- 20307251 TI - Polymeric micelles as a drug delivery system enhance cytotoxicity of vinorelbine through more intercellular accumulation. AB - Polymeric micelles had been used as an efficacious carrier system for anti-cancer drug delivery. However, it is not clear whether the molecular mechanism of drug encapsulated in micelles is same as free drug. In this study, the mechanism of vinorelbine loaded in glycol-phosphatidylethanolamine (PEG-PE) micelles (M-Vino) on tumor cells was investigated. Compared with free vinorelbine (Free Vino), M Vino was more effective in inhibiting the growth of tumor cells in vitro, inducing G(2)/M phase arrest and apoptosis of tumor cells. M-Vino showed a faster entry and higher accumulation in 4T1 cells than free vinorelbine. Therefore, M Vino destabilized microtubules, induced cell death, and enhanced its cytotoxicity through more intercellular accumulation of vinorelbine. PMID- 20307253 TI - Design of inductive sensors for tongue control system for computers and assistive devices. AB - PURPOSE: The paper introduces a novel design of air-core inductive sensors in printed circuit board (PCB) technology for a tongue control system. The tongue control system provides a quadriplegic person with a keyboard and a joystick type of mouse for interaction with a computer or for control of an assistive device. METHOD: Activation of inductive sensors was performed with a cylindrical, soft ferromagnetic material (activation unit). Comparative analysis of inductive sensors in PCB technology with existing hand-made inductive sensors was performed with respect to inductance, resistance, and sensitivity to activation when the activation unit was placed in the center of the sensor. Optimisation of the activation unit was performed in a finite element model. RESULTS: PCBs with air core inductive sensors were manufactured in a 10 layers, 100 microm and 120 microm line width technology. These sensors provided quality signals that could drive the electronics of the hand-made sensors. Furthermore, changing the geometry of the sensors allowed generation of variable signals correlated with the 2D movement of the activation unit at the sensors' surface. CONCLUSION: PCB technology for inductive sensors allows flexibility in design, automation of production and ease of possible integration with supplying electronics. The basic switch function of the inductive sensor can be extended to two-dimensional movement detection for pointing devices. PMID- 20307252 TI - Peripheral biomarkers do not correlate with cognitive impairment in highly active antiretroviral therapy-treated subjects with human immunodeficiency virus type 1 infection. AB - Neuropsychological (NP) impairments in human immunodeficiency virus (HIV) infected individuals remain high despite the introduction of highly active antiretroviral therapy (HAART). We sought to determine whether or not a monocyte gene expression profile along with other peripheral factors would correlate with neuropsychological impairment among HIV-infected individuals. Forty-four HIV-1 seropositive subjects (HIV+) on HAART and 11 HIV-1-seronegative controls (HIV-) had NP testing and blood drawn for monocyte gene expression analysis. All HIV+ subjects were assessed for CD4 counts, apolipoprotein E (ApoE) genotype, viral load, and plasma lipopolysaccharide (LPS) and soluble CD14 (sCD14). NP scores were normalized to age, gender, and education. Twenty-five percent of HIV+ individuals showed abnormal NP testing results (> 1.5 SD below normal in two domains). HIV+ individuals had deficits in attention/working memory, verbal learning, and information processing speed compared to HIV- controls. There was no correlation between overall NP impairment and plasma viral load, level of education, age, ethnic diversity, sCD14, plasma LPS, CD4 cell count, ApoE genotype, or years of infection. However, greater years of infection had worse visual learning performance. sCD14 and CD4 nadir positively correlated with information processing speed and fine motor skills, respectively. LPS correlated with viral load but not cognitive impairment. Monocyte gene expression confirmed a chronic inflammatory profile that correlated with viral load but not cognition. No blood index or profile was associated with overall NP impairment. PMID- 20307254 TI - Beyond the wheelchair: development of motorised transport for people with severe mobility impairments in developing countries. AB - PURPOSE: In developing countries, lack of over-the-road transportation reduces a vast number of disabled people to a life of begging, dependency and social isolation. Although there have been some excellent efforts to provide low-cost wheelchairs and hand-powered tricycles, little has been done to further provide transport for disabled people. METHODS: To address this problem directly we devised a low-cost motorised wheelchair transporter prototype (the Skeeter) using a combination of bicycle parts, a custom built frame, and an inexpensive small engine for propulsion. RESULTS: The Skeeter can provide independent operation and travel by a wheelchair user. It is an economically feasible solution to the lack of over-the-road transportation for people with mobility impairments in developing countries. CONCLUSIONS: The Skeeter has the potential to provide a major enhancement in the quality of life for people with disabilities in developing countries around the world. PMID- 20307255 TI - Pharmacological properties of thalidomide and its analogues. AB - Thalidomide and its immunomodulatory imide drugs (IMiDs) analogues CC-5013 (Revlimid, Lenalidomide) and CC-4047 (Actimid, Pomalidomide) have been used as anti-inflammatory and anticancerous drugs in the recent years. Thalidomide and IMiDs inhibit the cytokines tumour necrosis factor-alpha (TNF-alpha), interleukins (IL) 1-beta, 6, 12, and granulocyte macrophage-colony stimulating factor (GM-CSF). They also costimulate primary human T, NKT and NK lymphocytes inducing their proliferation, cytokine production, and cytotoxic activity. On the other hand, the compounds are anti-angiogenic, anti-proliferative, and pro apoptotic. Thalidomide analogues have been used as inhibitors of alpha glucosidase and could be potential drugs for diabetes treatment. In this review, we explore the current trend of the different structures, the new patents, and the possible new applications in different pathologies. PMID- 20307256 TI - Update information on drug metabolism systems--2009, part I. AB - The field of drug metabolism has changed dramatically in the past generation. Two of the driving forces are the advances in analytical chemistry and our understanding of the biological systems. With regard to the former, the advances in liquid chromatography-mass spectrometry (LC-MS) are extremely impressive, and the speed of analysis has been increased even more with the recent developments in ultraperformance LC (UPLC). NMR analysis on a sub-microgram scale is not unusual, and the 2-dimensional methods are also very impressive. The biology underlying gene regulation is highly developed, and the recombinant methods have greatly facilitated progress in the field. Today it is common to design discovery and development efforts focused on critical human phenomena from the very start, with animal studies supporting the efficacy and safety efforts. PMID- 20307258 TI - Novel insights into the assembly and function of human nuclear-encoded cytochrome c oxidase subunits 4, 5a, 6a, 7a and 7b. AB - Mammalian CcO (cytochrome c oxidase) is a hetero-oligomeric protein complex composed of 13 structural subunits encoded by both the mitochondrial and nuclear genomes. To study the role of nuclear-encoded CcO subunits in the assembly and function of the human complex, we used stable RNA interference of COX4, COX5A and COX6A1, as well as expression of epitope-tagged Cox6a, Cox7a and Cox7b, in HEK (human embryonic kidney)-293 cells. Knockdown of Cox4, Cox5a and Cox6a resulted in reduced CcO activity, diminished affinity of the residual enzyme for oxygen, decreased holoCcO and CcO dimer levels, increased accumulation of CcO subcomplexes and gave rise to an altered pattern of respiratory supercomplexes. An analysis of the patterns of CcO subcomplexes found in both knockdown and overexpressing cells identified a novel CcO assembly intermediate, identified the entry points of three late-assembled subunits and demonstrated directly the essential character as well as the interdependence of the assembly of Cox4 and Cox5a. The ectopic expression of the heart/muscle-specific isoform of the Cox6 subunit (COX6A2) resulted in restoration of both CcO holoenzyme and activity in COX6A1-knockdown cells. This was in sharp contrast with the unaltered levels of COX6A2 mRNA in these cells, suggesting the existence of a fixed expression programme. The normal amount and function of respiratory complex I in all of our CcO-deficient knockdown cell lines suggest that, unlike non-human CcO-deficient models, even relatively small amounts of CcO can maintain the normal biogenesis of this respiratory complex in cultured human cells. PMID- 20307259 TI - A role for Na+/H+ exchangers and intracellular pH in regulating vitamin C-driven electron transport across the plasma membrane. AB - Ascorbate (vitamin C) is the major electron donor to a tPMET (transplasma membrane electron transport) system that was originally identified in human erythrocytes. This plasma membrane redox system appears to transfer electrons from intracellular ascorbate to extracellular oxidants (e.g. non-transferrin bound iron). Although this phenomenon has been observed in nucleated cells, its mechanism and regulation are not well understood. In the present study we have examined both facets of this phenomenon in K562 cells and primary astrocyte cultures. Using ferricyanide as the analytical oxidant we demonstrate that tPMET is enhanced by dehydroascorbate uptake via facilitative glucose transporters, and subsequent accumulation of intracellular ascorbate. Additionally, we demonstrate that this stimulation is not due to ascorbate that is released from the cells, but is dependent only on a restricted intracellular pool of the vitamin. Substrate-saturation kinetics suggest an enzyme-catalysed reaction across the plasma membrane by an as-yet-unidentified reductase that relies on extensive recycling of intracellular ascorbate. Inhibition of ascorbate-stimulated tPMET by the NHE (Na(+)/H(+)-exchanger) inhibitors amiloride and 5-(N-ethyl-N isopropyl)amiloride, which is diminished by bicarbonate, suggests that tPMET activity may be regulated by intracellular pH. In support of this hypothesis, tPMET in astrocytes was significantly inhibited by ammonium chloride-pulse induced intracellular acidification, whereas it was significantly stimulated by bicarbonate-induced intracellular alkalinization. These results suggest that ascorbate-dependent tPMET is enzyme-catalysed and is modulated by NHE activity and intracellular pH. PMID- 20307260 TI - Myogenic regulatory factors transactivate the Tceal7 gene and modulate muscle differentiation. AB - Recurrent injuries eventually exhaust the capacity of skeletal muscle to fully restore or regenerate its cellular architecture. Therefore a comprehensive understanding of the muscle regeneration programme is needed to provide a platform for new therapies for devastating diseases such as Duchenne muscular dystrophy. To begin to decipher the molecular programme that directs muscle regeneration, we undertook an unbiased strategy using microarray analysis of cardiotoxin-injured skeletal muscle at defined time periods in the adult mouse. Using this strategy, we identified Tceal7 [transcription elongation factor A (SII)-like 7], which was dynamically regulated during muscle regeneration. Our studies revealed that Tceal7 was restricted to the skeletal muscle lineage during embryogenesis. Using transgenic technologies and transcriptional assays, we defined an upstream 0.7 kb fragment of the Tceal7 gene that directed the LacZ reporter to the developing skeletal muscle lineage. Analysis of the Tceal7 promoter revealed evolutionarily conserved E-box motifs within the 0.7 kb upstream fragment that were essential for promoter activity, as mutation of the E box motifs resulted in the loss of reporter expression in the somites of transgenic embryos. Furthermore, we demonstrated that MRFs (myogenic regulatory factors) were Tceal7 upstream transactivators using transcriptional assays, EMSAs (electrophoretic mobility-shift assays), and ChIP (chromatin immunoprecipitation) assays. Overexpression of Tceal7 in C2C12 myoblasts decreased cellular proliferation and enhanced differentiation. Further studies revealed that p27 expression was up-regulated following Tceal7 overexpression. These studies support the hypothesis that MRFs transactivate Tceal7 gene expression and promote muscle differentiation during muscle development and regeneration. PMID- 20307261 TI - Regulation of the miR-212/132 locus by MSK1 and CREB in response to neurotrophins. AB - Neurotrophins are growth factors that are important in neuronal development and survival as well as synapse formation and plasticity. Many of the effects of neurotrophins are mediated by changes in protein expression as a result of altered transcription or translation. To determine whether neurotrophins regulate the production of microRNAs (miRNAs), small RNA species that modulate protein translation or mRNA stability, we used deep sequencing to identify BDNF (brain derived neurotrophic factor)-induced miRNAs in cultured primary cortical mouse neurons. This revealed that the miR-212/132 cluster contained the miRNAs most responsive to BDNF treatment. This cluster was found to produce four miRNAs: miR 132, miR-132*, miR-212 and miR-212*. Using specific inhibitors, mouse models and promoter analysis we have shown that the regulation of the transcription of the miR-212/132 miRNA cluster and the miRNAs derived from it are regulated by the ERK1/2 (extracellular-signal-regulated kinase 1/2) pathway, via both MSK (mitogen and stress-activated kinase)-dependent and -independent mechanisms. PMID- 20307262 TI - Improvement of pain related self management for oncologic patients through a trans institutional modular nursing intervention: protocol of a cluster randomized multicenter trial. AB - BACKGROUND: Pain is one of the most frequent and distressing symptoms in cancer patients. For the majority of the patients, sufficient pain relief can be obtained if adequate treatment is provided. However, pain remains often undertreated due to institutional, health care professional and patient related barriers. Patients self management skills are affected by the patients' knowledge, activities and attitude to pain management. This trial protocol is aimed to test the SCION-PAIN program, a multi modular structured intervention to improve self management in cancer patients with pain. METHODS: 240 patients with diagnosed malignancy and pain > 3 days and average pain >or= 3/10 will participate in a cluster randomized trial on 18 wards in 2 German university hospitals. Patients from the intervention wards will receive, additionally to standard pain treatment, the SCION-PAIN program consisting of 3 modules: pharmacologic pain management, nonpharmacologic pain management and discharge management. The intervention will be conducted by specially trained oncology nurses and includes components of patient education, skills training and counseling to improve self care regarding pain management beginning with admission followed by booster session every 3rd day and one follow up telephone counseling within 2 to 3 days after discharge. Patients in the control group will receive standard care. Primary endpoint is the group difference in patient related barriers to management of cancer pain (BQII), 7 days after discharge. Secondary endpoints are: pain intensity & interference, adherence, coping and HRQoL. DISCUSSION: The study will determine if the acquired self management skills of the patients continue to be used after discharge from hospital. It is hypothesized that patients who receive the multi modular structured intervention will have less patient related barriers and a better self management of cancer pain. TRIAL REGISTRATION: ClinicalTrials NCT00779597. PMID- 20307263 TI - Asbestos, carbon nanotubes and the pleural mesothelium: a review of the hypothesis regarding the role of long fibre retention in the parietal pleura, inflammation and mesothelioma. AB - The unique hazard posed to the pleural mesothelium by asbestos has engendered concern in potential for a similar risk from high aspect ratio nanoparticles (HARN) such as carbon nanotubes. In the course of studying the potential impact of HARN on the pleura we have utilised the existing hypothesis regarding the role of the parietal pleura in the response to long fibres. This review seeks to synthesise our new data with multi-walled carbon nanotubes (CNT) with that hypothesis for the behaviour of long fibres in the lung and their retention in the parietal pleura leading to the initiation of inflammation and pleural pathology such as mesothelioma. We describe evidence that a fraction of all deposited particles reach the pleura and that a mechanism of particle clearance from the pleura exits, through stomata in the parietal pleura. We suggest that these stomata are the site of retention of long fibres which cannot negotiate them leading to inflammation and pleural pathology including mesothelioma. We cite thoracoscopic data to support the contention, as would be anticipated from the preceding, that the parietal pleura is the site of origin of pleural mesothelioma. This mechanism, if it finds support, has important implications for future research into the mesothelioma hazard from HARN and also for our current view of the origins of asbestos-initiated pleural mesothelioma and the common use of lung parenchymal asbestos fibre burden as a correlate of this tumour, which actually arises in the parietal pleura. PMID- 20307264 TI - Transcriptional profiling of an Fd-GOGAT1/GLU1 mutant in Arabidopsis thaliana reveals a multiple stress response and extensive reprogramming of the transcriptome. AB - BACKGROUND: Glutamate plays a central position in the synthesis of a variety of organic molecules in plants and is synthesised from nitrate through a series of enzymatic reactions. Glutamate synthases catalyse the last step in this pathway and two types are present in plants: NADH- or ferredoxin-dependent. Here we report a genome wide microarray analysis of the transcriptional reprogramming that occurs in leaves and roots of the A. thaliana mutant glu1-2 knocked-down in the expression of Fd-GOGAT1 (GLU1; At5g04140), one of the two genes of A. thaliana encoding ferredoxin-dependent glutamate synthase. RESULTS: Transcriptional profiling of glu1-2 revealed extensive changes with the expression of more than 5500 genes significantly affected in leaves and nearly 700 in roots. Both genes involved in glutamate biosynthesis and transformation are affected, leading to changes in amino acid compositions as revealed by NMR metabolome analysis. An elevated glutamine level in the glu1-2 mutant was the most prominent of these changes. An unbiased analysis of the gene expression datasets allowed us to identify the pathways that constitute the secondary response of an FdGOGAT1/GLU1 knock-down. Among the most significantly affected pathways, photosynthesis, photorespiratory cycle and chlorophyll biosynthesis show an overall downregulation in glu1-2 leaves. This is in accordance with their slight chlorotic phenotype. Another characteristic of the glu1-2 transcriptional profile is the activation of multiple stress responses, mimicking cold, heat, drought and oxidative stress. The change in expression of genes involved in flavonoid biosynthesis is also revealed. The expression of a substantial number of genes encoding stress-related transcription factors, cytochrome P450 monooxygenases, glutathione S-transferases and UDP-glycosyltransferases is affected in the glu1-2 mutant. This may indicate an induction of the detoxification of secondary metabolites in the mutant. CONCLUSIONS: Analysis of the glu1-2 transcriptome reveals extensive changes in gene expression profiles revealing the importance of Fd-GOGAT1, and indirectly the central role of glutamate, in plant development. Besides the effect on genes involved in glutamate synthesis and transformation, the glu1-2 mutant transcriptome was characterised by an extensive secondary response including the downregulation of photosynthesis-related pathways and the induction of genes and pathways involved in the plant response to a multitude of stresses. PMID- 20307265 TI - Uncoupled responses of Smad4-deficient cancer cells to TNFalpha result in secretion of monomeric laminin-gamma2. AB - BACKGROUND: Functional loss of the tumor suppressor Smad4 is involved in pancreatic and colorectal carcinogenesis and has been associated with the acquisition of invasiveness. We have previously demonstrated that the heterotrimeric basement membrane protein laminin-332 is a Smad4 target. Namely, Smad4 functions as a positive transcriptional regulator of all three genes encoding laminin-332; its loss is thus implicated in the reduced or discontinuous deposition of the heterotrimeric basement membrane molecule as evident in carcinomas. Uncoupled expression of laminin genes, on the other hand, namely overexpression of the laminin-gamma2 chain is an impressive marker at invasive edges of carcinomas where tumor cells are maximally exposed to signals from stromal cell types like macrophages. As Smad4 is characterized as an integrator of multiple extracellular stimuli in a strongly contextual manner, we asked if loss of Smad4 may also be involved in uncoupled expression of laminin genes in response to altered environmental stimuli. Here, we address Smad4 dependent effects of the prominent inflammatory cytokine TNFalpha on tumor cells. RESULTS: Smad4-reconstituted colon carcinoma cells like adenoma cells respond to TNFalpha with an increased expression of all three chains encoding laminin-332; coincubation with TGFbeta and TNFalpha leads to synergistic induction and to the secretion of large amounts of the heterotrimer. In contrast, in Smad4-deficient cells TNFalpha can induce expression of the gamma2 and beta3 but not the alpha3 chain. Surprisingly, this uncoupled induction of laminin-332 chains in Smad4 negative cells rather than causing intracellular accumulation is followed by the release of gamma2 into the medium, either in a monomeric form or in complexes with as yet unknown proteins. Soluble gamma2 is associated with increased cell migration. CONCLUSIONS: Loss of Smad4 may lead to uncoupled induction of laminin gamma2 in response to TNFalpha and may therefore represent one of the mechanisms which underlie accumulation of laminin-gamma2 at the invasive margin of a tumor. The finding, that gamma2 is secreted from tumor cells in significant amounts and is associated with increased cell migration may pave the way for further investigation to better understand its functional relevance for tumor progression. PMID- 20307266 TI - Computerized general practice based networks yield comparable performance with sentinel data in monitoring epidemiological time-course of influenza-like illness and acute respiratory illness. AB - BACKGROUND: Computerized morbidity registration networks might serve as early warning systems in a time where natural epidemics such as the H1N1 flu can easily spread from one region to another. METHODS: In this contribution we examine whether general practice based broad-spectrum computerized morbidity registration networks have the potential to act as a valid surveillance instrument of frequently occurring diseases. We compare general practice based computerized data assessing the frequency of influenza-like illness (ILI) and acute respiratory infections (ARI) with data from a well established case-specific sentinel network, the European Influenza Surveillance Scheme (EISS). The overall frequency and trends of weekly ILI and ARI data are compared using both networks. RESULTS: Detection of influenza-like illness and acute respiratory illness occurs equally fast in EISS and the computerized network. The overall frequency data for ARI are the same for both networks, the overall trends are similar, but the increases and decreases in frequency do not occur in exactly the same weeks. For ILI, the overall rate was slightly higher for the computerized network population, especially before the increase of ILI, the overall trend was almost identical and the increases and decreases occur in the same weeks for both networks. CONCLUSIONS: Computerized morbidity registration networks are a valid tool for monitoring frequent occurring respiratory diseases and the detection of sudden outbreaks. PMID- 20307267 TI - Thyroid function in children with growth hormone (GH) deficiency during the initial phase of GH replacement therapy - clinical implications. AB - BACKGROUND: Normal thyroid hormone secretion or appropriate L-thyroxine (L-T4) substitution is necessary for the optimal effect of the growth hormone (GH) administration on growth rate. The decrease of free thyroxine (FT4) levels at recombinant human GH (rhGH) therapy onset has been reported in several studies. The aim of the present study was to evaluate the effect of rhGH administration on thyrotropin (TSH) and FT4 serum concentrations in children with GH deficiency (GHD) during the 1st year of therapy, as well as to assess potential indications to thyroid hormone supplementation in them. PATIENTS AND METHODS: The analysis involved data of 75 children (59 boys, 16 girls) with disorders of GH secretion (GHD, neurosecretory dysfunction - NSD) and partial GH inactivity (inactGH), who were treated with rhGH for - at least - one year. In all the children, body height and height velocity (HV) were assessed before and after 1 year of therapy, while TSH, FT4, IGF-I and IGFBP-3 before treatment and after 3-6 months and 1 year of treatment. In the patients, who revealed hypothyroidism (HypoT), an appropriate L-T4 substitution was introduced immediately. The incidence of HypoT, occurring during the initial phase of rhGH therapy, was assessed, as well as its influence on the therapy effectiveness. RESULTS: Before rhGH substitution, there were no significant differences in either auxological indices or TSH and FT4 secretion, or IGF-I concentration and its bioavailability among the groups of patients. During the initial 3-6 months of rhGH administration, a significant decrease of FT4 serum concentration, together with a significant increase of IGF I SDS and IGF-I/IGFBP-3 molar ratio was observed in all the studied groups. In 17 children, HypoT was diagnosed and L-T4 substitution was administered. Despite similar IGF-I secretion increase, the improvement of HV presented significantly lower in children with HypoT than in those who remained euthyroid all the time. CONCLUSIONS: The incidence of HypoT during the initial phase of GH treatment in children with GHD and the negative effect of even transient thyroid hormone deficiency on the growth rate should be taken into account. PMID- 20307268 TI - A single blind randomized controlled trial of cognitive behavioural therapy in a help-seeking population with an At Risk Mental State for psychosis: the Dutch Early Detection and Intervention Evaluation (EDIE-NL) trial. AB - BACKGROUND: Psychotic disorders are a serious mental health problem. Intervention before the onset of psychosis might result in delaying the onset, reducing the impact or even preventing the first episode of psychosis. This study explores the effectiveness of cognitive behavioural therapy (CBT) in targeting cognitive biases that are involved in the formation of delusions in persons with an ultra high risk for developing psychosis. A single blind randomised controlled trial compares CBT with treatment as usual in preventing or delaying the onset of psychosis. METHOD/DESIGN: All help seeking patients aged 14 to 35 years referred to the mental health services in three regions in the Netherlands are pre screened with the Prodromal Questionnaire during a period of two years. Patients with a score of 18 or more on the sub-clinical positive symptoms items (45 items in total) will be assessed with the Comprehensive Assessment of At Risk Mental State (CAARMS). In a different pathway to care model all referrals from the mental health services in Amsterdam to the specialized psychosis clinic of the Academic Medical Centre in Amsterdam are also assessed with the CAARMS. The primary outcome is the transition rate to psychosis according to the CAARMS criteria. Group differences will be analysed with chi-square tests and survival analyses. DISCUSSION: CBT is a highly tolerated treatment. The psycho-educational CBT approach may prove to be a successful strategy since most people with an At Risk Mental State (ARMS) are distressed by odd disturbing experiences. Giving explanations for and normalising these experiences may reduce the arousal (distress) and therefore may prevent people from developing a catastrophic delusional explanation for their odd experiences and thus prevent them from developing psychosis.Screening the entire help-seeking population referred to community mental health services with a two-stage strategy, as compared with traditional referral to a specialist clinical psychosis centre, might detect more ultra-high-risk (UHR) patients. This type of screening could be implemented in mental health care as routine screening. The trial is registered at Current Controlled trials as trial number ISRCTN21353122. PMID- 20307269 TI - Selective accumulation of langerhans-type dendritic cells in small airways of patients with COPD. AB - BACKGROUND: Dendritic cells (DC) linking innate and adaptive immune responses are present in human lungs, but the characterization of different subsets and their role in COPD pathogenesis remain to be elucidated. The aim of this study is to characterize and quantify pulmonary myeloid DC subsets in small airways of current and ex-smokers with or without COPD. METHODS: Myeloid DC were characterized using flowcytometry on single cell suspensions of digested human lung tissue. Immunohistochemical staining for langerin, BDCA-1, CD1a and DC-SIGN was performed on surgical resection specimens from 85 patients. Expression of factors inducing Langerhans-type DC (LDC) differentiation was evaluated by RT-PCR on total lung RNA. RESULTS: Two segregated subsets of tissue resident pulmonary myeloid DC were identified in single cell suspensions by flowcytometry: the langerin+ LDC and the DC-SIGN+ interstitial-type DC (intDC). LDC partially expressed the markers CD1a and BDCA-1, which are also present on their known blood precursors. In contrast, intDC did not express langerin, CD1a or BDCA-1, but were more closely related to monocytes.Quantification of DC in the small airways by immunohistochemistry revealed a higher number of LDC in current smokers without COPD and in COPD patients compared to never smokers and ex smokers without COPD. Importantly, there was no difference in the number of LDC between current and ex-smoking COPD patients.In contrast, the number of intDC did not differ between study groups. Interestingly, the number of BDCA-1+ DC was significantly lower in COPD patients compared to never smokers and further decreased with the severity of the disease. In addition, the accumulation of LDC in the small airways significantly correlated with the expression of the LDC inducing differentiation factor activin-A. CONCLUSIONS: Myeloid DC differentiation is altered in small airways of current smokers and COPD patients resulting in a selective accumulation of the LDC subset which correlates with the pulmonary expression of the LDC-inducing differentiation factor activin-A. This study identified the LDC subset as an interesting focus for future research in COPD pathogenesis. PMID- 20307270 TI - Effects of antenatal dexamethasone treatment on glucocorticoid receptor and calcyon gene expression in the prefrontal cortex of neonatal and adult common marmoset monkeys. AB - BACKGROUND: Synthetic glucocorticoids such as dexamethasone (DEX) are commonly used to promote fetal lung maturation in at-risk preterm births, but there is emerging evidence of subsequent neurobehavioral abnormalities in these children e.g. problems with inattention/hyperactivity. However, molecular pathways mediating effects of glucocorticoid overexposure on motor and cognitive development are poorly understood. METHODS: In this study with common marmoset monkeys, we investigated for neonatal and adulthood effects of antenatal DEX treatment on the expression of the corticosteroid receptors and also calcyon, a risk gene for attention-deficit/hyperactivity disorder, in the prefrontal cortex (PFC). Pregnant marmosets were exposed to DEX (5 mg/kg body weight) or vehicle during early (days 42-48) or late (days 90-96) stages of the 144-day pregnancy. RESULTS: In neonates, relative to controls, glucocorticoid receptor (GR) mRNA levels were significantly reduced after the late DEX treatment in the medial, orbital and dorsal PFC and after the early DEX treatment in the dorsal PFC. The early DEX exposure, specifically, resulted in significant reduction in calcyon mRNA expression in the medial, orbital, dorsal and lateral PFC relative to controls. Mineralocorticoid receptor (MR) mRNA levels were not significantly affected by DEX treatment. In adults, PFC GR, calcyon, and MR mRNA levels were not significantly affected by early or late prenatal DEX treatment. CONCLUSION: These findings indicate that antenatal DEX treatment could lead to short-term alterations in PFC expression of the GR and calcyon genes, with possible neurodevelopmental functional consequences. PMID- 20307271 TI - Gastric glomus tumor: a case report. AB - Gastric glomus tumors are rare mesenchymal tumors of the gastrointestinal tract. We describe a 72-year-old patient who presented with episodes of melena and was subsequently investigated for a tumor of the antrum of the stomach. Surgical resection revealed a 2 x 2 x 1.7 cm well circumscribed submucosal tumor, extending into the muscularis propria. The histopathologic examination of the specimen demonstrated a glomus tumor of the stomach. We discuss the preoperative investigation, the diagnostic problems and the surgical treatment of the patient with this rare submucosal lesion. PMID- 20307272 TI - Interferon-gamma inhibits interleukin-1beta-induced matrix metalloproteinase production by synovial fibroblasts and protects articular cartilage in early arthritis. AB - INTRODUCTION: The first few months after symptom onset represents a pathologically distinct phase in rheumatoid arthritis (RA). We used relevant experimental models to define the pathological role of interferon-gamma (IFN gamma) during early inflammatory arthritis. METHODS: We studied IFN-gamma's capacity to modulate interleukin-1beta (IL-1beta) induced degenerative responses using RA fibroblast-like synoviocytes (FLS), a bovine articular cartilage explant (BACE)/RA-FLS co-culture model and an experimental inflammatory arthritis model (murine antigen-induced arthritis (AIA)). RESULTS: IFN-gamma modulated IL-1beta driven matrix metalloproteinases (MMP) synthesis resulting in the down-regulation of MMP-1 and MMP-3 production in vitro. IFN-gamma did not affect IL-1beta induced tissue inhibitor of metalloproteinase-1 (TIMP-1) production by RA FLS but skewed the MMP/TIMP-1 balance sufficiently to attenuate glycosaminoglycan-depletion in our BACE model. IFN-gamma reduced IL-1beta expression in the arthritic joint and prevented cartilage degeneration on Day 3 of AIA. CONCLUSIONS: Early therapeutic intervention with IFN-gamma may be critical to orchestrate tissue-protective responses during inflammatory arthritis. PMID- 20307273 TI - Reasons for participating in randomised controlled trials: conditional altruism and considerations for self. AB - BACKGROUND: Randomised controlled trials of healthcare interventions depend on the participation of volunteers who might not derive any personal health benefit from their participation. The idea that altruistic-type motives are important for trial participation is understandably widespread, but recent studies suggest considerations of personal benefit can influence participation decisions in various ways. METHODS: Non-participant observation of recruitment consultations (n = 25) and in-depth interviews with people invited to participate in the UK REFLUX trial (n = 13). RESULTS: Willingness to help others and to contribute towards furthering medical knowledge featured strongly among the reasons people gave for being interested in participating in the trial. But decisions to attend recruitment appointments and take part were not based solely on consideration of others. Rather, they were presented as conditional on individuals additionally perceiving some benefit (and no significant disadvantage) for themselves. Potential for personal benefit or disadvantage could be seen in both the interventions being evaluated and trial processes. CONCLUSIONS: The term 'conditional altruism' concisely describes the willingness to help others that may initially incline people to participate in a trial, but that is unlikely to lead to trial participation in practice unless people also recognise that participation will benefit them personally. Recognition of conditional altruism has implications for planning trial recruitment communications to promote informed and voluntary trial participation. TRIAL REGISTRATION: ISRCTN15517081. PMID- 20307274 TI - Environmental distribution of prokaryotic taxa. AB - BACKGROUND: The increasing availability of gene sequences of prokaryotic species in samples extracted from all kind of locations allows addressing the study of the influence of environmental patterns in prokaryotic biodiversity. We present a comprehensive study to address the potential existence of environmental preferences of prokaryotic taxa and the commonness of the specialist and generalist strategies. We also assessed the most significant environmental factors shaping the environmental distribution of taxa. RESULTS: We used 16S rDNA sequences from 3,502 sampling experiments in natural and artificial sources. These sequences were taxonomically assigned, and the corresponding samples were also classified into a hierarchical classification of environments. We used several statistical methods to analyze the environmental distribution of taxa. Our results indicate that environmental specificity is not very common at the higher taxonomic levels (phylum to family), but emerges at lower taxonomic levels (genus and species). The most selective environmental characteristics are those of animal tissues and thermal locations. Salinity is another very important factor for constraining prokaryotic diversity. On the other hand, soil and freshwater habitats are the less restrictive environments, harboring the largest number of prokaryotic taxa. All information on taxa, samples and environments is provided at the envDB online database, http://metagenomics.uv.es/envDB. CONCLUSIONS: This is, as far as we know, the most comprehensive assessment of the distribution and diversity of prokaryotic taxa and their associations with different environments. Our data indicate that we are still far from characterizing prokaryotic diversity in any environment, except, perhaps, for human tissues such as the oral cavity and the vagina. PMID- 20307275 TI - Truncus arteriosus with aortic arch interruption: cardiovascular magnetic resonance findings in the unrepaired adult. AB - Truncus arteriosus (TA) is a rare congenital condition defined as a single arterial vessel arising from the heart that gives origin to the systemic, pulmonary and coronary circulations. We discuss the unique case of a 28 year-old female patient with unrepaired TA and interruption of the aortic arch who underwent cardiovascular magnetic resonance (CMR). PMID- 20307276 TI - Specific expression profile and prognostic significance of peroxiredoxins in grade II-IV astrocytic brain tumors. AB - BACKGROUND: Peroxiredoxins (Prxs) have recently been suggested to have a role in tumorigenesis. METHODS: We studied the expression of Prx I-VI and their relationship to patient survival in 383 grade II-IV diffuse astrocytic brain tumors. RESULTS: Prx I positivity was found in 68%, Prx II in 84%, Prx III in 90%, Prx IV in 5%, Prx V in 4% and Prx VI in 47% of the tumors. Prx I and Prx II expression decreased significantly with increasing malignancy grade (p < 0.001 and p < 0.001). Patients with Prx I or Prx II positive tumors were significantly younger than the average age of all the patients (p = 0.014 and p = 0.005). A lower proliferation rate was associated with Prx I and Prx VI positive tumors (p = 0.019 and p = 0.033), and a lower apoptotic rate was found within Prx I and Prx II positive tumors (p < 0.001 and p = 0.007). Patients with Prx I and Prx II positive tumors had a significantly better survival rate than their Prx-negative counterparts (p = 0.0052 and p = 0.0002). CONCLUSION: The expression of Prx I and Prx II correlates with astrocytic tumor features, such as grade and patient age and proliferation activity (Prx I), and accordingly with patient survival. PMID- 20307277 TI - Development of a SNP resource and a genetic linkage map for Atlantic cod (Gadus morhua). AB - BACKGROUND: Atlantic cod (Gadus morhua) is a species with increasing economic significance for the aquaculture industry. The genetic improvement of cod will play a critical role in achieving successful large-scale aquaculture. While many microsatellite markers have been developed in cod, the number of single nucleotide polymorphisms (SNPs) is currently limited. Here we report the identification of SNPs from sequence data generated by a large-scale expressed sequence tag (EST) program, focusing on fish originating from Canadian waters. RESULTS: A total of 97976 ESTs were assembled to generate 13448 contigs. We detected 4753 SNPs that met our selection criteria (depth of coverage > or = 4 reads; minor allele frequency > 25%). 3072 SNPs were selected for testing. The percentage of successful assays was 75%, with 2291 SNPs amplifying correctly. Of these, 607 (26%) SNPs were monomorphic for all populations tested. In total, 64 (4%) of SNPs are likely to represent duplicated genes or highly similar members of gene families, rather than alternative alleles of the same gene, since they showed a high frequency of heterozygosity. The remaining polymorphic SNPs (1620) were categorised as validated SNPs. The mean minor allele frequency of the validated loci was 0.258 (+/- 0.141). Of the 1514 contigs from which validated SNPs were selected, 31% have a significant blast hit. For the SNPs predicted to occur in coding regions (141), we determined that 36% (51) are non-synonymous. Many loci (1033 SNPs; 64%) are polymorphic in all populations tested. However a small number of SNPs (184) that are polymorphic in the Western Atlantic were monomorphic in fish tested from three European populations. A preliminary linkage map has been constructed with 23 major linkage groups and 924 mapped SNPs. CONCLUSIONS: These SNPs represent powerful tools to accelerate the genetic improvement of cod aquaculture. They have been used to build a genetic linkage map that can be applied to quantitative trait locus (QTL) discovery. Since these SNPs were generated from ESTs, they are linked to specific genes. Genes that map within QTL intervals can be prioritized for testing to determine whether they contribute to observed phenotypes. PMID- 20307278 TI - Work and diet-related risk factors of cardiovascular diseases: comparison of two occupational groups. AB - BACKGROUND: Although work related risk factors associated with Cardiovascular Diseases (CD) have been well researched, there is no detailed knowledge regarding disparate occupational groups each with a different risk exposition. Therefore, two occupational groups (chefs and office workers) were compared with a focus on nutritional and psychosocial factors. METHODS: Two groups of subjects were tested for work and diet-related risks of CD (45 chefs and 48 office workers). The groups matched both for gender (male) and age (30 to 45 years). The study included a medical check-up, bioelectrical impedance analysis as well as an evaluation of questionnaires on health, nutritional behaviour and coping capacity. In addition, volunteers were required to compile a 7-day-dietary-record and collect their urine 24 h prior to their check-up. Blood samples drawn were analysed for glucose and lipid metabolism, homocysteine, vitamin B12, folic acid; C-reactive protein, uric acid, red blood cell fatty acids, plant sterols, antioxidative capacity and oxidative stress. RESULTS: On average, the chefs showed one risk factor more compared to the office workers. The most frequent risk factors in both groups included overweight/obesity (chef group [CG]: 62.2%; office group [OG]: 58.3%) and elevated TC (CG: 62.2%; OG: 43.8%]. Moreover, although the chefs often had higher CRP-concentrations (40.0%), more office workers suffered from hypertension (37.5%).Chefs showed significant higher concentrations of saturated fatty acids and oleic acid, whereas docosahexaenoic acid, Omega-6- and trans fatty acids were found more frequently in the red blood cell membranes of office workers. While there were no significant differences in analysed plant sterols between the two occupational groups, 7,8-dihydro-8-oxo-2' deoxyguanosine was significantly increased in office workers.Concerning the work related psychosocial factors, the chefs were characterised by a stronger subjective importance of work, a greater degree of professional aspiration and enhanced efforts at perfectionism at their workplace. CONCLUSIONS: The chefs in the study bear a higher risk of CD compared to the office-workers. Although, CD is not exclusively a result of workplace-conditions, study results show that work related influences can not be ignored. Thus, prevention of CD may be an important task attributable to occupational physicians. PMID- 20307279 TI - Improving pairwise sequence alignment accuracy using near-optimal protein sequence alignments. AB - BACKGROUND: While the pairwise alignments produced by sequence similarity searches are a powerful tool for identifying homologous proteins - proteins that share a common ancestor and a similar structure; pairwise sequence alignments often fail to represent accurately the structural alignments inferred from three dimensional coordinates. Since sequence alignment algorithms produce optimal alignments, the best structural alignments must reflect suboptimal sequence alignment scores. Thus, we have examined a range of suboptimal sequence alignments and a range of scoring parameters to understand better which sequence alignments are likely to be more structurally accurate. RESULTS: We compared near optimal protein sequence alignments produced by the Zuker algorithm and a set of probabilistic alignments produced by the probA program with structural alignments produced by four different structure alignment algorithms. There is significant overlap between the solution spaces of structural alignments and both the near optimal sequence alignments produced by commonly used scoring parameters for sequences that share significant sequence similarity (E-values < 10-5) and the ensemble of probA alignments. We constructed a logistic regression model incorporating three input variables derived from sets of near-optimal alignments: robustness, edge frequency, and maximum bits-per-position. A ROC analysis shows that this model more accurately classifies amino acid pairs (edges in the alignment path graph) according to the likelihood of appearance in structural alignments than the robustness score alone. We investigated various trimming protocols for removing incorrect edges from the optimal sequence alignment; the most effective protocol is to remove matches from the semi-global optimal alignment that are outside the boundaries of the local alignment, although trimming according to the model-generated probabilities achieves a similar level of improvement. The model can also be used to generate novel alignments by using the probabilities in lieu of a scoring matrix. These alignments are typically better than the optimal sequence alignment, and include novel correct structural edges. We find that the probA alignments sample a larger variety of alignments than the Zuker set, which more frequently results in alignments that are closer to the structural alignments, but that using the probA alignments as input to the regression model does not increase performance. CONCLUSIONS: The pool of suboptimal pairwise protein sequence alignments substantially overlaps structure based alignments for pairs with statistically significant similarity, and a regression model based on information contained in this alignment pool improves the accuracy of pairwise alignments with respect to structure-based alignments. PMID- 20307280 TI - Effect of the CB1 cannabinoid agonist WIN 55212-2 on the acquisition and reinstatement of MDMA-induced conditioned place preference in mice. AB - BACKGROUND: Numerous reports indicate that MDMA users consume other psychoactive drugs, among which cannabis is one of the most common. The aim of the present study was to evaluate, using the conditioned place preference, the effect of the cannabinoid agonist WIN 55,212-2 on the rewarding effects of MDMA in mice. METHODS: In the first experiment adolescent mice were initially conditioned with 1.25, 2.5 or 5 mg/kg of MDMA or 0.1 or 0.5 mg/kg of WIN and subsequently with both drugs. Reinstatement of the extinguished preference by priming doses was performed in the groups that showed CPP. In the second experiment, animals were conditioned with 2.5 or 5 mg/kg of MDMA and, after extinction, reinstatement of the preference was induced by 0.5 or 0.1 mg/kg of WIN. RESULTS: A low dose of WIN 55212-2 (0.1 mg/kg) increased the rewarding effects of low doses of MDMA (1.25 mg/kg), although a decrease in the preference induced by MDMA (5 and 2.5 mg/kg) was observed when the dose of WIN 55212-2 was raised (0.5 mg/kg). The CB1 antagonist SR 141716 also increased the rewarding effects of the lowest MDMA dose and did not block the effects of WIN. Animals treated with the highest WIN dose plus a non-neurotoxic dose of MDMA exhibited decreases of striatal DA and serotonin in the cortex. On the other hand, WIN 55212-2-induced CPP was reinstated by priming injections of MDMA, although WIN did not reinstate the MDMA induced CPP. CONCLUSIONS: These results confirm that the cannabinoid system plays a role in the rewarding effects of MDMA and highlights the risks that sporadic drug use can pose in terms of relapse to dependence. Finally, the potential neuroprotective action of cannabinoids is not supported by our data; on the contrary, they are evidence of the potential neurotoxic effect of said drugs when administered with MDMA. PMID- 20307281 TI - Current sample size conventions: flaws, harms, and alternatives. AB - BACKGROUND: The belief remains widespread that medical research studies must have statistical power of at least 80% in order to be scientifically sound, and peer reviewers often question whether power is high enough. DISCUSSION: This requirement and the methods for meeting it have severe flaws. Notably, the true nature of how sample size influences a study's projected scientific or practical value precludes any meaningful blanket designation of <80% power as "inadequate". In addition, standard calculations are inherently unreliable, and focusing only on power neglects a completed study's most important results: estimates and confidence intervals. Current conventions harm the research process in many ways: promoting misinterpretation of completed studies, eroding scientific integrity, giving reviewers arbitrary power, inhibiting innovation, perverting ethical standards, wasting effort, and wasting money. Medical research would benefit from alternative approaches, including established value of information methods, simple choices based on cost or feasibility that have recently been justified, sensitivity analyses that examine a meaningful array of possible findings, and following previous analogous studies. To promote more rational approaches, research training should cover the issues presented here, peer reviewers should be extremely careful before raising issues of "inadequate" sample size, and reports of completed studies should not discuss power. SUMMARY: Common conventions and expectations concerning sample size are deeply flawed, cause serious harm to the research process, and should be replaced by more rational alternatives. PMID- 20307282 TI - Phylodynamics of HIV-1 circulating recombinant forms 12_BF and 38_BF in Argentina and Uruguay. AB - BACKGROUND: Although HIV-1 CRF12_BF and CRF38_BF are two epidemiologically important recombinant lineages circulating in Argentina and Uruguay, little is known about their population dynamics. METHODS: A total of 120 "CRF12_BF-like" and 20 "CRF38_BF-like" pol recombinant sequences collected in Argentina and Uruguay from 1997 to 2009 were subjected to phylogenetic and Bayesian coalescent based analyses to estimate evolutionary and demographic parameters. RESULTS: Phylogenetic analyses revealed that CRF12_BF viruses from Argentina and Uruguay constitute a single epidemic with multiple genetic exchanges among countries; whereas circulation of the CRF38_BF seems to be confined to Uruguay. The mean estimated substitution rate of CRF12_BF at pol gene (2.5 x 10-3 substitutions/site/year) was similar to that previously described for subtype B. According to our estimates, CRF12_BF and CRF38_BF originated at 1983 (1978-1988) and 1986 (1981-1990), respectively. After their emergence, the CRF12_BF and CRF38_BF epidemics seem to have experienced a period of rapid expansion with initial growth rates of around 1.2 year-1 and 0.9 year-1, respectively. Later, the rate of spread of these CRFs_BF seems to have slowed down since the mid 1990s. CONCLUSIONS: Our results suggest that CRF12_BF and CRF38_BF viruses were generated during the 1980s, shortly after the estimated introduction of subtype F1 in South America (~1975-1980). After an initial phase of fast exponential expansion, the rate of spread of both CRFs_BF epidemics seems to have slowed down, thereby following a demographic pattern that resembles those previously reported for the HIV-1 epidemics in Brazil, USA, and Western Europe. PMID- 20307283 TI - "Well, it's nobody's responsibility but my own." A qualitative study to explore views about the determinants of health and prevention of knee pain in older adults. AB - BACKGROUND: Dahlgren and Whitehead's 'rainbow' outlines key determinants of health and has been widely adopted within public health policy and research. Public understanding regarding the determinants of health is, however, relatively unknown, particularly in relation to common chronic joint problems like knee pain. We aimed to explore individual attitudes to the prevention of knee pain, and assess how people make sense of their lives by using the rainbow model to explore social determinants of health. METHODS: Twenty-eight semi-structured interviews were undertaken with older adults living in the community. The format of the interview enabled individuals to first tell their story, then the rainbow picture was used to further prompt discussion. Interviews were digitally recorded and transcripts were fully transcribed. Qualitative computer software package NVivo 2 was used to manage the data. Thematic analysis was undertaken. RESULTS: Individual responsibility for health was a dominant theme although the role of health and statutory services was also recognised. Barriers to uptake of prevention activities included cultural perceptions, attitudes towards work and perceived costs of prevention activities. Participants used the rainbow for locating their personal life within a wider social, economic and policy context. CONCLUSIONS: People view individual responsibility as key to maintaining health and draw upon the past, present and future expectations when considering social determinants of their health. The rainbow picture does have relevance at the individual level and can help to formulate more dynamic and contextualised approaches to the prevention of health conditions in community living adults. PMID- 20307284 TI - RBC and WBC fatty acid composition following consumption of an omega 3 supplement: lessons for future clinical trials. AB - BACKGROUND: Results from increasing numbers of in vitro and in vivo studies have demonstrated that omega 3 fatty acids incorporated in cell culture media or in the diet of the animals can suppress the growth of cancers. When human clinical trials are initiated to determine the ability of omega 3 fatty acids to alter growth or response to chemotherapeutic interventions of cancers, it will be essential to determine the omega 3 intake of individuals in the trial to determine compliance with consumption of the supplement and to correlate with endpoints of efficacy. We wondered if the fatty acid composition of RBCs might accurately indicate incorporation of omega 3 fatty acids in the WBCs. In this report we determine and compare the changes in fatty acid compositions of red blood cells and white blood cells in response to consumption of three doses of an omega 3 fatty acid supplement. RESULTS: We found that the fraction of omega 3 fatty acids in both red blood cells and white blood cells increased following consumption of the supplement. There was a linear, dose responsive increase in the fraction of omega 3 fatty acids in red blood cells but the increase in omega 3 in white blood cells was not linear. The magnitude of increase in omega 3 fatty acids was different between the two cell types. CONCLUSIONS: Fatty acid analysis of red blood cells is a good measure of compliance with supplement consumption. However, fatty acid analysis of white blood cells is needed to correlate changes in fatty acid composition of white blood cells with other biochemical changes in the white blood cells. TRIAL REGISTRATION: ClinicalTrials.gov NCT00899353. PMID- 20307285 TI - Identification of recurrent regions of Copy-Number Variants across multiple individuals. AB - BACKGROUND: Algorithms and software for CNV detection have been developed, but they detect the CNV regions sample-by-sample with individual-specific breakpoints, while common CNV regions are likely to occur at the same genomic locations across different individuals in a homogenous population. Current algorithms to detect common CNV regions do not account for the varying reliability of the individual CNVs, typically reported as confidence scores by SNP-based CNV detection algorithms. General methodologies for identifying these recurrent regions, especially those directed at SNP arrays, are still needed. RESULTS: In this paper, we describe two new approaches for identifying common CNV regions based on (i) the frequency of occurrence of reliable CNVs, where reliability is determined by high confidence scores, and (ii) a weighted frequency of occurrence of CNVs, where the weights are determined by the confidence scores. In addition, motivated by the fact that we often observe partially overlapping CNV regions as a mixture of two or more distinct subregions, regions identified using the two approaches can be fine-tuned to smaller sub-regions using a clustering algorithm. We compared the performance of the methods with sequencing-based results in terms of discordance rates, rates of departure from Hardy-Weinberg equilibrium (HWE) and average frequency and size of the identified regions. The discordance rates as well as the rates of departure from HWE decrease when we select CNVs with higher confidence scores. We also performed comparisons with two previously published methods, STAC and GISTIC, and showed that the methods we consider are better at identifying low-frequency but high-confidence CNV regions. CONCLUSIONS: The proposed methods for identifying common CNV regions in multiple individuals perform well compared to existing methods. The identified common regions can be used for downstream analyses such as group comparisons in association studies. PMID- 20307286 TI - Accumulation of phenanthrene by roots of intact wheat (Triticum acstivnm L.) seedlings: passive or active uptake? AB - BACKGROUND: Polycyclic aromatic hydrocarbons (PAHs) are of particular concern due to their hydrophobic, recalcitrant, persistent, potentially carcinogenic, mutagenic and toxic properties, and their ubiquitous occurrence in the environment. Most of the PAHs in the environment are present in surface soil. Plants grown in PAH-contaminated soils or water can become contaminated with PAHs because of their uptake. Therefore, they may threaten human and animal health. However, the mechanism for PAHs uptake by crop roots is little understood. It is important to understand exactly how PAHs are transported into the plant root system and into the human food chain, since it is beneficial in governing crop contamination by PAHs, remedying soils or waters polluted by PAHs with plants, and modeling potential uptake for risk assessment. RESULTS: The possibility that plant roots may take up phenanthrene (PHE), a representative of PAHs, via active process was investigated using intact wheat (Triticum acstivnm L.) seedlings in a series of hydroponic experiments. The time course for PHE uptake into wheat roots grown in Hoagland solution containing 5.62 microM PHE for 36 h could be separated into two periods: a fast uptake process during the initial 2 h and a slow uptake component thereafter. Concentration-dependent PHE uptake was characterized by a smooth, saturable curve with an apparent Km of 23.7 microM and a Vmax of 208 nmol g(-1) fresh weight h(-1), suggesting a carrier-mediated uptake system. Competition between PHE and naphthalene for their uptake by the roots further supported the carrier-mediated uptake system. Low temperature and 2,4 dinitrophenol (DNP) could inhibit PHE uptake equally, indicating that metabolism plays a role in PHE uptake. The inhibitions by low temperature and DNP were strengthened with increasing concentration of PHE in external solution within PHE water solubility (7.3 muM). The contribution of active uptake to total absorption was almost 40% within PHE water solubility. PHE uptake by wheat roots caused an increase in external solution pH, implying that wheat roots take up PHE via a PHE/nH+ symport system. CONCLUSION: It is concluded that an active, carrier mediated and energy-consuming influx process is involved in the uptake of PHE by plant roots. PMID- 20307288 TI - Does commitment to rehabilitation influence clinical outcome of total hip resurfacing arthroplasty? AB - BACKGROUND: The purpose of this study was to evaluate whether compliance and rehabilitative efforts were predictors of early clinical outcome of total hip resurfacing arthroplasty. METHODS: A cross-sectional survey was utilized to collect information from 147 resurfacing patients, who were operated on by a single surgeon, regarding their level of commitment to rehabilitation following surgery. Patients were followed for a mean of 52 months (range, 24 to 90 months). Clinical outcomes and functional capabilities were assessed utilizing the Harris hip objective rating system, the SF-12 Health Survey, and an eleven-point satisfaction score. A linear regression analysis was used to determine whether there was any correlation between the rehabilitation commitment scores and any of the outcome measures, and a multivariate regression model was used to control for potentially confounding factors. RESULTS: Overall, an increased level of commitment to rehabilitation was positively correlated with each of the following outcome measures: SF-12 Mental Component Score, SF-12 Physical Component Score, Harris Hip score, and satisfaction scores. These correlations remained statistically significant in the multivariate regression model. CONCLUSIONS: Patients who were more committed to their therapy after hip resurfacing returned to higher levels of functionality and were more satisfied following their surgery. PMID- 20307287 TI - Biological species is the only possible form of existence for higher organisms: the evolutionary meaning of sexual reproduction. AB - Consistent holistic view of sexual species as the highest form of biological existence is presented. The Weismann's idea that sex and recombination provide the variation for the natural selection to act upon is dominated in most discussions of the biological meaning of the sexual reproduction. Here, the idea is substantiated that the main advantage of sex is the opposite: the ability to counteract not only extinction but further evolution as well. Living systems live long owing to their ability to reproduce themselves with a high fidelity. Simple organisms (like bacteria) reach the continued existence due to the high fidelity of individual genome replication. In organisms with a large genome and complex development, the achievable fidelity of DNA replication is not enough for the precise reproduction of the genome. Such species must be capable of surviving and must remain unchanged in spite of the continuous changes of their genes. This problem has no solution in the frame of asexual ("homeogenomic") lineages. They would rapidly degrade and become extinct or blurred out in the course of the reckless evolution. The core outcome of the transition to sexual reproduction was the creation of multiorganismic entity - biological species. Individual organisms forfeited their ability to reproduce autonomously. It implies that individual organisms forfeited their ability to substantive evolution. They evolve as a part of the biological species. In case of obligatory sexuality, there is no such a thing as synchronic multi-level selection. Natural selection cannot select anything that is not a unit of reproduction. Hierarchy in biology implies the functional predestination of the parts for the sake of the whole. A crucial feature of the sexual reproduction is the formation of genomes of individual organisms by random picking them over from the continuously shuffled gene pool instead of the direct replication of the ancestor's genome. A clear anti evolutionary consequence of the sexuality is evident from the fact that the genotypes of the individuals with an enhanced competitiveness are not transmitted to the next generation. Instead, after mating with "ordinary" individuals, these genotypes scatter and rearrange in new gene combinations, thus preventing the winner from exploiting the success. PMID- 20307289 TI - Does computer use pose a hazard for future long-term sickness absence? AB - The aim of the study was to investigate if weekly duration of computer use predicted sickness absence for more than two weeks at a later time.A cohort of 2146 frequent computer users filled in a questionnaire at baseline and was followed for one year with continuously recording of the duration of computer use and furthermore followed for 300 weeks in a central register of sickness absence for more than 2 weeks.147 participants of the 2,146 (6.9%) became first time sick listed in the follow-up period. Overall, mean weekly computer use did not turn out to be a risk factor for later sickness absence. The hazard ratio for sickness absence with weekly increase of one hour in computer use was 0.99 (95% CI: 0.99 to 1.00). Low satisfaction with work place arrangements and female gender both doubled the risk of sickness absence.We have earlier found that computer use did not predict persistent pain in the neck and upper limb, and it seems that computer use neither predicts future long-term sickness absence of all causes. PMID- 20307290 TI - Paniya Voices: a Participatory Poverty and Health Assessment among a marginalized South Indian tribal population. AB - BACKGROUND: In India, indigenous populations, known as Adivasi or Scheduled Tribes (STs), are among the poorest and most marginalized groups. 'Deprived' ST groups tend to display high levels of resignation and to lack the capacity to aspire; consequently their health perceptions often do not adequately correspond to their real health needs. Moreover, similar to indigenous populations elsewhere, STs often have little opportunity to voice perspectives framed within their own cultural worldviews. We undertook a study to gather policy-relevant data on the views, experiences, and priorities of a marginalized and previously enslaved tribal group in South India, the Paniyas, who have little 'voice' or power over their own situation. METHODS/DESIGN: We implemented a Participatory Poverty and Health Assessment (PPHA). We adopted guiding principles and an ethical code that promote respect for Paniya culture and values. The PPHA, informed by a vulnerability framework, addressed five key themes (health and illness, well-being, institutions, education, gender) using participatory approaches and qualitative methods. We implemented the PPHA in five Paniya colonies (clusters of houses in a small geographical area) in a gram panchayat (lowest level decentralized territorial unit) to generate data that can be quickly disseminated to decision-makers through interactive workshops and public forums. PRELIMINARY FINDINGS: Findings indicated that the Paniyas are caught in multiple 'vulnerability traps', that is, they view their situation as vicious cycles from which it is difficult to break free. CONCLUSION: The PPHA is a potentially useful approach for global health researchers working with marginalized communities to implement research initiatives that will address those communities' health needs in an ethical and culturally appropriate manner. PMID- 20307291 TI - Use of complementary and alternative medicines by a sample of Turkish women for infertility enhancement: a descriptive study. AB - BACKGROUND: Infertility patients are a vulnerable group that often seeks a non medical solution for their failure to conceive. World-wide, women use CAM for productive health, but only a limited number of studies report on CAM use to enhance fertility. Little is known about traditional and religious forms of therapies that are used in relation to conventional medicine in Turkey. We investigated the prevalence and types of complementary and alternative medicine (CAM) used by infertile Turkish women for fertility enhancement. METHODS: A face to-face questionnaire inquiring demographic information and types of CAM used for fertility enhancement were completed by hundred infertility patients admitted to a primary care family planning centre in Van, Turkey between January and July 2009. RESULTS: The vast majority of infertile women had used CAM at least once for infertility. CAM use included religious interventions, herbal products and recommendations of traditional "hodja's" (faith healers). Of these women, 87.8% were abused in the last 12 months, 36.6% felt not being supported by her partner and 80.5% had never spoken with a physician about CAM. CONCLUSIONS: Infertile Turkish women use complementary medicine frequently for fertility enhancement and are in need of information about CAM. Religious and traditional therapies are used as an adjunct to, rather than a substitute for, conventional medical therapy. Physicians need to approach fertility patients with sensitivity and should be able to council their patients about CAM accordingly. PMID- 20307292 TI - Phenotypic analysis of images of zebrafish treated with Alzheimer's gamma secretase inhibitors. AB - BACKGROUND: Several gamma-secretase inhibitors (GSI) are in clinical trials for the treatment of Alzheimer's disease (AD). This enzyme mediates the proteolytic cleavage of amyloid precursor protein (APP) to generate amyloid beta protein, Abeta, the pathogenic protein in AD. The gamma-secretase also cleaves Notch to generate Notch Intracellular domain (NICD), the signaling molecule that is implicated in tumorigenesis. RESULTS: We have developed a method to examine live zebrafish that were each treated with gamma-secretase inhibitors (GSI), DAPT {N- [N-(3,5-Difluorophenacetyl-L-alanyl)]-S-phenylglycine t-Butyl Ester}, Gleevec, or fragments of Gleevec. These compounds were first tested in a cell-based assay and the effective concentrations of these compounds that blocked Abeta generation were quantitated. The mortality of zebrafish, as a result of exposure to different doses of compound, was assessed, and any apoptotic processes were examined by TUNEL staining. We then used conventional and automatic microscopes to acquire images of zebrafish and applied algorithms to automate image composition and processing. Zebrafish were treated in 96- or 384-well plates, and the phenotypes were analyzed at 2, 3 and 5 days post fertilization (dpf). We identified that AD95, a fragment of Gleevec, effectively blocks Abeta production and causes specific phenotypes that were different from those treated with DAPT. Finally, we validated the specificity of two Notch phenotypes (pigmentation and the curvature of tail/trunk) induced by DAPT in a dose-dependent manner. These phenotypes were examined in embryos treated with GSIs or AD95 at increasing concentrations. The expression levels of Notch target gene her6 were also measured by in situ hybridization and the co-relationship between the levels of Notch inhibition by DAPT and AD95 and the severity of phenotypes were determined. CONCLUSION: The results reported here of the effects on zebrafish suggest that this newly developed method may be used to screen novel GSIs and other leads for a variety of therapeutic indications. PMID- 20307293 TI - Denitrification in human dental plaque. AB - BACKGROUND: Microbial denitrification is not considered important in human associated microbial communities. Accordingly, metabolic investigations of the microbial biofilm communities of human dental plaque have focused on aerobic respiration and acid fermentation of carbohydrates, even though it is known that the oral habitat is constantly exposed to nitrate (NO3-) concentrations in the millimolar range and that dental plaque houses bacteria that can reduce this NO3- to nitrite (NO2-). RESULTS: We show that dental plaque mediates denitrification of NO3- to nitric oxide (NO), nitrous oxide (N2O), and dinitrogen (N2) using microsensor measurements, 15N isotopic labelling and molecular detection of denitrification genes. In vivo N2O accumulation rates in the mouth depended on the presence of dental plaque and on salivary NO3- concentrations. NO and N2O production by denitrification occurred under aerobic conditions and was regulated by plaque pH. CONCLUSIONS: Increases of NO concentrations were in the range of effective concentrations for NO signalling to human host cells and, thus, may locally affect blood flow, signalling between nerves and inflammatory processes in the gum. This is specifically significant for the understanding of periodontal diseases, where NO has been shown to play a key role, but where gingival cells are believed to be the only source of NO. More generally, this study establishes denitrification by human-associated microbial communities as a significant metabolic pathway which, due to concurrent NO formation, provides a basis for symbiotic interactions. PMID- 20307294 TI - Protection from annual flooding is correlated with increased cholera prevalence in Bangladesh: a zero-inflated regression analysis. AB - BACKGROUND: Alteration of natural or historical aquatic flows can have unintended consequences for regions where waterborne diseases are endemic and where the epidemiologic implications of such change are poorly understood. The implementation of flood protection measures for a portion of an intensely monitored population in Matlab, Bangladesh, allows us to examine whether cholera outcomes respond positively or negatively to measures designed to control river flooding. METHODS: Using a zero inflated negative binomial model, we examine how selected covariates can simultaneously account for household clusters reporting no cholera from those with positive counts as well as distinguishing residential areas with low counts from areas with high cholera counts. Our goal is to examine how residence within or outside a flood protected area interacts with the probability of cholera presence and the effect of flood protection on the magnitude of cholera prevalence. RESULTS: In Matlab, living in a household that is protected from annual monsoon flooding appears to have no significant effect on whether the household experiences cholera, net of other covariates. However, counter-intuitively, among households where cholera is reported, living within the flood protected region significantly increases the number of cholera cases. CONCLUSIONS: The construction of dams or other water impoundment strategies for economic or social motives can have profound and unanticipated consequences for waterborne disease. Our results indicate that the construction of a flood control structure in rural Bangladesh is correlated with an increase in cholera cases for residents protected from annual monsoon flooding. Such a finding requires attention from both the health community and from governments and non governmental organizations involved in ongoing water management schemes. PMID- 20307295 TI - In silico fragmentation for computer assisted identification of metabolite mass spectra. AB - BACKGROUND: Mass spectrometry has become the analytical method of choice in metabolomics research. The identification of unknown compounds is the main bottleneck. In addition to the precursor mass, tandem MS spectra carry informative fragment peaks, but the coverage of spectral libraries of measured reference compounds are far from covering the complete chemical space. Compound libraries such as PubChem or KEGG describe a larger number of compounds, which can be used to compare their in silico fragmentation with spectra of unknown metabolites. RESULTS: We created the MetFrag suite to obtain a candidate list from compound libraries based on the precursor mass, subsequently ranked by the agreement between measured and in silico fragments. In the evaluation MetFrag was able to rank most of the correct compounds within the top 3 candidates returned by an exact mass query in KEGG. Compared to a previously published study, MetFrag obtained better results than the commercial MassFrontier software. Especially for large compound libraries, the candidates with a good score show a high structural similarity or just different stereochemistry, a subsequent clustering based on chemical distances reduces this redundancy. The in silico fragmentation requires less than a second to process a molecule, and MetFrag performs a search in KEGG or PubChem on average within 30 to 300 seconds, respectively, on an average desktop PC. CONCLUSIONS: We presented a method that is able to identify small molecules from tandem MS measurements, even without spectral reference data or a large set of fragmentation rules. With today's massive general purpose compound libraries we obtain dozens of very similar candidates, which still allows a confident estimate of the correct compound class. Our tool MetFrag improves the identification of unknown substances from tandem MS spectra and delivers better results than comparable commercial software. MetFrag is available through a web application, web services and as java library. The web frontend allows the end user to analyse single spectra and browse the results, whereas the web service and console application are aimed to perform batch searches and evaluation. PMID- 20307296 TI - Dietary patterns of adults living in Ouagadougou and their association with overweight. AB - BACKGROUND: Urbanization in developing countries comes along with changes in food habits and living conditions and with an increase in overweight and associated health risks. The objective of the study was to describe dietary patterns of adults in Ouagadougou and to study their relationship with anthropometric status of the subjects. METHODS: A qualitative food frequency questionnaire was administered to 1,072 adults living in two contrasted districts of Ouagadougou. Dietary patterns were defined by principal component analysis and described by multivariate analysis. Logistic regression was used to study their association with overweight. RESULTS: The diet was mainly made of cereals, vegetables and fats from vegetable sources. The two first components of the principal component analysis were interpreted respectively as a "snacking" score and as a "modern foods" score. Both scores were positively and independently associated with the economic level of households and with food expenditures (p 25 kg/m2). A higher "modern foods" score was associated with a higher prevalence of overweight when confounding factors were accounted for (OR = 1.19 [95% CI 1.03-1.36]) but there was no relationship between overweight and the "snacking" score. CONCLUSIONS: Modernisation of types of foods consumed was associated with the living conditions and the environment and with an increased risk of overweight. This should be accounted for to promote better nutrition and prevent non communicable diseases. PMID- 20307297 TI - A comparison of perioperative outcomes of video-assisted thoracic surgical (VATS) lobectomy with open thoracotomy and lobectomy: results of an analysis using propensity score based weighting. AB - BACKGROUND: Randomized trials comparing VATS lobectomy to open lobectomy are of small size. We analyzed a case-control series using propensity score-weighting to adjust for important covariates in order to compare the clinical outcomes of the two techniques. METHODS: We compared patients undergoing lobectomy for clinical stage I lung cancer (NSCLC) by either VATS or open (THOR) methods. Inverse probability of treatment weighted estimators, with weights derived from propensity scores, were used to adjust cohorts for determinants of perioperative morbidity and mortality including age, gender, preop FEV1, ASA class, and Charlson Comorbidity Index (CCI). Bootstrap methods provided standard errors. Endpoints were postoperative stay (LOS), chest tube duration, complications, and lymph node retrieval. RESULTS: We analyzed 136 consecutive lobectomy patients. Operative mortality was 1/62 (1.6%) for THOR and 1/74 (1.4%) for VATS, P = 1.00. 5/74 (6.7%) VATS were converted to open procedures. Adjusted median LOS was 7 days (THOR) versus 4 days (VATS), P < 0.0001, HR = 0.33. Adjusted median chest tube duration (days) was 5 (THOR) versus 3 (VATS), P < 0.0001, HR = 0.42. Complication rates were 39% (THOR) versus 34% (VATS), P = 0.61. Adjusted mean number of lymph nodes dissected per patient was 18.1 (THOR) versus 14.8 (VATS), p = 0.17. CONCLUSIONS: After balancing covariates that affect morbidity, mortality and LOS in this case-control series using propensity-weighting, the results confirm that VATS lobectomy is associated with a statistically significant shorter LOS, similar mortality and complication rates and similar rates of lymph node removal in patients with clinical stage I NSCLC. PMID- 20307298 TI - Orchestrated transcription of biological processes in the marine picoeukaryote Ostreococcus exposed to light/dark cycles. AB - BACKGROUND: Picoeukaryotes represent an important, yet poorly characterized component of marine phytoplankton. The recent genome availability for two species of Ostreococcus and Micromonas has led to the emergence of picophytoplankton comparative genomics. Sequencing has revealed many unexpected features about genome structure and led to several hypotheses on Ostreococcus biology and physiology. Despite the accumulation of genomic data, little is known about gene expression in eukaryotic picophytoplankton. RESULTS: We have conducted a genome wide analysis of gene expression in Ostreococcus tauri cells exposed to light/dark cycles (L/D). A Bayesian Fourier Clustering method was implemented to cluster rhythmic genes according to their expression waveform. In a single L/D condition nearly all expressed genes displayed rhythmic patterns of expression. Clusters of genes were associated with the main biological processes such as transcription in the nucleus and the organelles, photosynthesis, DNA replication and mitosis. CONCLUSIONS: Light/Dark time-dependent transcription of the genes involved in the main steps leading to protein synthesis (transcription basic machinery, ribosome biogenesis, translation and aminoacid synthesis) was observed, to an unprecedented extent in eukaryotes, suggesting a major input of transcriptional regulations in Ostreococcus. We propose that the diurnal co regulation of genes involved in photoprotection, defence against oxidative stress and DNA repair might be an efficient mechanism, which protects cells against photo-damage thereby, contributing to the ability of O. tauri to grow under a wide range of light intensities. PMID- 20307299 TI - Long-term survival of cancer patients compared to heart failure and stroke: a systematic review. AB - BACKGROUND: Cancer, heart failure and stroke are among the most common causes of death worldwide. Investigation of the prognostic impact of each disease is important, especially for a better understanding of competing risks. Aim of this study is to provide an overview of long term survival of cancer, heart failure and stroke patients based on the results of large population- and hospital-based studies. METHODS: Records for our study were identified by searches of Medline via Pubmed. We focused on observed and relative age- and sex-adjusted 5-year survival rates for cancer in general and for the four most common malignancies in developed countries, i.e. lung, breast, prostate and colorectal cancer, as well as for heart failure and stroke. RESULTS: Twenty studies were identified and included for analysis. Five-year observed survival was about 43% for all cancer entities, 40-68% for stroke and 26-52% for heart failure. Five-year age and sex adjusted relative survival was 50-57% for all cancer entities, about 50% for stroke and about 62% for heart failure. In regard to the four most common malignancies in developed countries 5-year relative survival was 12-18% for lung cancer, 73-89% for breast cancer, 50-99% for prostate cancer and about 43-63% for colorectal cancer. Trend analysis revealed a survival improvement over the last decades. CONCLUSIONS: The results indicate that long term survival and prognosis of cancer is not necessarily worse than that of heart failure and stroke. However, a comparison of the prognostic impact of the different diseases is limited, corroborating the necessity for further systematic investigation of competing risks. PMID- 20307300 TI - Annual variations in the number of malaria cases related to two different patterns of Anopheles darlingi transmission potential in the Maroni area of French Guiana. AB - BACKGROUND: With an Annual Parasite Incidence (API) of 132.1, in the high and moderate risks zones, the Maroni area of French Guiana has the second highest malaria incidence of South-America after Guyana (API = 183.54) and far above Brazil (API = 28.25). Malaria transmission is occurring despite strong medical assistance and active vector control, based on general WHO recommendations. This situation is generated by two main factors that are the social and cultural characteristics of this border area, where several ethnic groups are living, and the lack of understanding of transmission dynamics of the main mosquito vector, Anopheles darlingi. In this context, entomological data collected in two villages belonging to two different ethnic groups of the French border of the Maroni River, were retrospectively analysed to find out how the mosquito bionomics are related to the malaria transmission patterns. METHODS: Data were provided by human landing catches of mosquitoes carried out each month for two years in two villages belonging to two ethnic groups, the Amerindians Wayanas and the Aloukous of African origin. The mosquitoes were sorted by species, sex, date, hour and place of collection and processed for Plasmodium sp. parasite detection. The data were compiled to provide the following variables: human biting rates (HBR), parity rates (PR), numbers of infective bites (IB), entomological inoculation rates (EIR) and numbers of infected mosquitoes surviving enough to transmit (IMT). Spatial and temporal differences of variables between locations and during the night were tested by the Kruskall-Wallis analysis of variance to find out significant variations. RESULTS: The populations of the main mosquito vector An. darlingi showed significant variations in the spatial and temporal HBR/person/night and HBR/person/hour, IB/person/month and IB/person/hour, and IMT/village/night and IMT/village/hour. In the village of Loca (Aloukous), the IMT peaked from June to August with a very low transmission during the other months. The risks were higher during the first part of the night and an EIR of 10 infective bites per person and per year was estimated. In the village of Twenke (Wayanas), high level of transmission was reported all year with small peaks in March and October. The risk was higher during the second part of the night and an EIR of 5 infective bites per person and per year was estimated. CONCLUSION: For the first time in the past 40 years, the mosquito bionomics was related to the malaria transmission patterns in French Guiana. The peak of malaria cases reported from August to October in the Maroni region is concomitant with the significant peak of An. darlingi IMT, reported from the village of Loca where transmission is higher. However, the persistent number of cases reported all year long may also be related to the transmission in the Amerindian villages. The An. darlingi bionomics for these two close populations were found significantly different and may explain why a uniform vector control method is inadequate. Following these findings, malaria prevention measures adapted to the local conditions are needed. Finally, the question of the presence of An. darlingi sub species is raised. PMID- 20307301 TI - Prediction of haplotypes for ungenotyped animals and its effect on marker assisted breeding value estimation. AB - BACKGROUND: In livestock populations, missing genotypes on a large proportion of animals are a major problem to implement the estimation of marker-assisted breeding values using haplotypes. The objective of this article is to develop a method to predict haplotypes of animals that are not genotyped using mixed model equations and to investigate the effect of using these predicted haplotypes on the accuracy of marker-assisted breeding value estimation. METHODS: For genotyped animals, haplotypes were determined and for each animal the number of haplotype copies (nhc) was counted, i.e. 0, 1 or 2 copies. In a mixed model framework, nhc for each haplotype were predicted for ungenotyped animals as well as for genotyped animals using the additive genetic relationship matrix. The heritability of nhc was assumed to be 0.99, allowing for minor genotyping and haplotyping errors. The predicted nhc were subsequently used in marker-assisted breeding value estimation by applying random regression on these covariables. To evaluate the method, a population was simulated with one additive QTL and an additive polygenic genetic effect. The QTL was located in the middle of a haplotype based on SNP-markers. RESULTS: The accuracy of predicted haplotype copies for ungenotyped animals ranged between 0.59 and 0.64 depending on haplotype length. Because powerful BLUP-software was used, the method was computationally very efficient. The accuracy of total EBV increased for genotyped animals when marker-assisted breeding value estimation was compared with conventional breeding value estimation, but for ungenotyped animals the increase was marginal unless the heritability was smaller than 0.1. Haplotypes based on four markers yielded the highest accuracies and when only the nearest left marker was used, it yielded the lowest accuracy. The accuracy increased with increasing marker density. Accuracy of the total EBV approached that of gene-assisted BLUP when 4-marker haplotypes were used with a distance of 0.1 cM between the markers. CONCLUSIONS: The proposed method is computationally very efficient and suitable for marker-assisted breeding value estimation in large livestock populations including effects of a number of known QTL. Marker-assisted breeding value estimation using predicted haplotypes increases accuracy especially for traits with low heritability. PMID- 20307302 TI - Computer-assisted resilience training to prepare healthcare workers for pandemic influenza: a randomized trial of the optimal dose of training. AB - BACKGROUND: Working in a hospital during an extraordinary infectious disease outbreak can cause significant stress and contribute to healthcare workers choosing to reduce patient contact. Psychological training of healthcare workers prior to an influenza pandemic may reduce stress-related absenteeism, however, established training methods that change behavior and attitudes are too resource intensive for widespread use. This study tests the feasibility and effectiveness of a less expensive alternative - an interactive, computer-assisted training course designed to build resilience to the stresses of working during a pandemic. METHODS: A "dose-finding" study compared pre-post changes in three different durations of training. We measured variables that are likely to mediate stress responses in a pandemic before and after training: confidence in support and training, pandemic-related self-efficacy, coping style and interpersonal problems. RESULTS: 158 hospital workers took the course and were randomly assigned to the short (7 sessions, median cumulative duration 111 minutes), medium (12 sessions, 158 minutes) or long (17 sessions, 223 minutes) version. Using an intention-to-treat analysis, the course was associated with significant improvements in confidence in support and training, pandemic self-efficacy and interpersonal problems. Participants who under-utilized coping via problem solving or seeking support or over-utilized escape-avoidance experienced improved coping. Comparison of doses showed improved interpersonal problems in the medium and long course but not in the short course. There was a trend towards higher drop-out rates with longer duration of training. CONCLUSIONS: Computer-assisted resilience training in healthcare workers appears to be of significant benefit and merits further study under pandemic conditions. Comparing three "doses" of the course suggested that the medium course was optimal. PMID- 20307303 TI - A novel LMNA mutation (R189W) in familial dilated cardiomyopathy: evidence for a 'hot spot' region at exon 3: a case report. AB - We describe a case of a patient with idiopathic dilated cardiomyopathy and cardiac conduction abnormalities who presented a strong family history of sudden cardiac death. Genetic screening of lamin A/C gene revealed in proband the presence of a novel missense mutation (R189W), near the most prevalent lamin A/C mutation (R190W), suggesting a "hot spot" region at exon 3. PMID- 20307304 TI - Low-density lipoprotein particle size in hepatic steatosis and metabolic syndrome. AB - BACKGROUND: Hepatic steatosis (HS), the most frequent liver disorder, was reported to be an independent predictor of cardiovascular disease. HS, if combined with the metabolic syndrome (MetS), might have a synergistic effect on low-density lipoprotein (LDL) particle size. METHODS: Carotid intima-media thickness (IMT) and plaque formation, and HS were diagnosed ultrasonographically, and the MetS was diagnosed using the ATP III criteria in 274 healthy workers (mean age +/- SD, 43.5 +/- 7.1 yrs). LDL particle size was measured with density gradient ultracentrifugation, and subfractions were classified as large, buoyant LDL I (27.2 to approximately 28.5 nm) and small, dense LDL III (24.2~25.5). All participants were grouped into three categories: control, subjects with HS alone and those with both HS and the MetS. RESULTS: The subjects with HS alone were 84 (30.7%), whereas those with HS and the MetS were 46 (16.8%). LDL peak particle sizes showed significant negative correlations with carotid mean IMTs. LDL peak particle size and LDL I (%) decreased significantly in the HS, showing the lowest values in the subjects with both HS and the MetS, and their association was independent, even adjusted for potential confounders. LDL III also showed independent associations across the groups. CONCLUSION: HS alone was more prevalent than HS combined with the MetS in general population. For the patients with HS alone, LDL particle size and carotid atherosclerosis were found to fall in the middle of the control and those with both HS and the MetS. PMID- 20307305 TI - Apples and oranges: avoiding different priors in Bayesian DNA sequence analysis. AB - BACKGROUND: One of the challenges of bioinformatics remains the recognition of short signal sequences in genomic DNA such as donor or acceptor splice sites, splicing enhancers or silencers, translation initiation sites, transcription start sites, transcription factor binding sites, nucleosome binding sites, miRNA binding sites, or insulator binding sites. During the last decade, a wealth of algorithms for the recognition of such DNA sequences has been developed and compared with the goal of improving their performance and to deepen our understanding of the underlying cellular processes. Most of these algorithms are based on statistical models belonging to the family of Markov random fields such as position weight matrix models, weight array matrix models, Markov models of higher order, or moral Bayesian networks. While in many comparative studies different learning principles or different statistical models have been compared, the influence of choosing different prior distributions for the model parameters when using different learning principles has been overlooked, and possibly lead to questionable conclusions. RESULTS: With the goal of allowing direct comparisons of different learning principles for models from the family of Markov random fields based on the same a-priori information, we derive a generalization of the commonly-used product-Dirichlet prior. We find that the derived prior behaves like a Gaussian prior close to the maximum and like a Laplace prior in the far tails. In two case studies, we illustrate the utility of the derived prior for a direct comparison of different learning principles with different models for the recognition of binding sites of the transcription factor Sp1 and human donor splice sites. CONCLUSIONS: We find that comparisons of different learning principles using the same a-priori information can lead to conclusions different from those of previous studies in which the effect resulting from different priors has been neglected. We implement the derived prior is implemented in the open-source library Jstacs to enable an easy application to comparative studies of different learning principles in the field of sequence analysis. PMID- 20307306 TI - A proteomic study of cMyc improvement of CHO culture. AB - BACKGROUND: The biopharmaceutical industry requires cell lines to have an optimal proliferation rate and a high integral viable cell number resulting in a maximum volumetric recombinant protein product titre. Nutrient feeding has been shown to boost cell number and productivity in fed-batch culture, but cell line engineering is another route one may take to increase these parameters in the bioreactor. The use of CHO-K1 cells with a c-myc plasmid allowing for over expressing c-Myc (designated cMycCHO) gives a higher integral viable cell number. In this study the differential protein expression in cMycCHO is investigated using two-dimensional gel electrophoresis (2-DE) followed by image analysis to determine the extent of the effect c-Myc has on the cell and the proteins involved to give the new phenotype. RESULTS: Over 100 proteins that were differentially expressed in cMycCHO cells were detected with high statistical confidence, of which 41 were subsequently identified by tandem mass spectrometry (LC-MS/MS). Further analysis revealed proteins involved in a variety of pathways. Some examples of changes in protein expression include: an increase in nucleolin, involved in proliferation and known to aid in stabilising anti-apoptotic protein mRNA levels, the cytoskeleton and mitochondrial morphology (vimentin), protein biosynthesis (eIF6) and energy metabolism (ATP synthetase), and a decreased regulation of all proteins, identified, involved in matrix and cell to cell adhesion. CONCLUSION: These results indicate several proteins involved in proliferation and adhesion that could be useful for future approaches to improve proliferation and decrease adhesion of CHO cell lines which are difficult to adapt to suspension culture. PMID- 20307307 TI - Gamma knife radiosurgery for essential tremor: a case report and review of the literature. AB - Approximately 5 million people in America are affected by essential tremors (ET), which are classified as a type of benign movement disorder. This disease manifests as tremors that usually occur in the hands, but they may also be present in the head, face, tongue, and lower limbs. Radiofrequency thalamotomy (RF) and deep brain stimulation (DBS) are common invasive procedures with proven track records that are used to treat ET. Although these procedures have high success rates, they still put patients at risk of potential side effects and are invasive by nature. Thalamotomy using the gamma knife (GK) also produces favorable outcomes in treating tremors, without the complications associated with invasive neurosurgery procedures. This report describes the presenting symptoms and extended treatment outcome for a patient with an advanced case of ET, who received GK thalamotomy treatment six years ago. Because of this non-invasive treatment, she regained the ability to paint and live with an improved quality of life. We also discuss and review the relevant literature regarding the risks and benefits of this treatment modality. GK thalamotomy is one effective option for the treatment of ET, and due to its noninvasive nature, it has a different risk profile than neurosurgery. We suggest that GK thalamotomy should be presented as one viable treatment option to all ET patients, and should be recommended to those who would be best served by less invasive treatment techniques. PMID- 20307308 TI - In situ protein expression in tumour spheres: development of an immunostaining protocol for confocal microscopy. AB - BACKGROUND: Multicellular tumour sphere models have been shown to closely mimic phenotype characteristics of in vivo solid tumours, or to allow in vitro propagation of cancer stem cells (CSCs). CSCs are usually characterized by the expression of specific membrane markers using flow cytometry (FC) after enzymatic dissociation. Consequently, the spatial location of positive cells within spheres is not documented. Confocal microscopy is the best technique for the imaging of thick biological specimens after multi-labelling but suffers from poor antibody penetration. Thus, we describe here a new protocol for in situ confocal imaging of protein expression in intact spheroids. METHODS: Protein expression in whole spheroids (150 mum in diameter) from two human colon cancer cell lines, HT29 and CT320X6, has been investigated with confocal immunostaining, then compared with profiles obtained through paraffin immunohistochemistry (pIHC) and FC. Target antigens, relevant for colon cancer and with different expression patterns, have been studied. RESULTS: We first demonstrate that our procedure overcomes the well known problem of antibody penetration in compact structures by performing immunostaining of EpCAM, a membrane protein expressed by all cells within our spheroids. EpCAM expression is detected in all cells, even the deepest ones. Likewise, antibody access is confirmed with CK20 and CD44 immunostaining. Confocal imaging shows that 100% of cells express beta-catenin, mainly present in the plasma membrane with also cytoplasmic and nuclear staining, in agreement with FC and pIHC data. pIHC and confocal imaging show similar CA 19-9 cytoplasmic and membranar expression profile in a cell subpopulation. CA 19-9+ cell count confirms confocal imaging as a highly sensitive method (75%, 62% and 51%, for FC, confocal imaging and pIHC, respectively). Finally, confocal imaging reveals that the weak expression of CD133, a putative colon CSC marker, is restricted to the luminal cell surface of colorectal cancer acini, with CD133+ cellular debris into glandular lumina. CONCLUSION: The present protocol enables in situ visualization of protein expression in compact three-dimensional models by whole mount confocal imaging, allowing the accurate localization and quantification of cells expressing specific markers. It should prove useful to study rare events like CSCs within tumour spheres. PMID- 20307310 TI - The failure of routine rapid HIV testing: a case study of improving low sensitivity in the field. AB - BACKGROUND: The rapid HIV antibody test is the diagnostic tool of choice in low and middle-income countries. Previous evidence suggests that rapid HIV diagnostic tests may underperform in the field, failing to detect a substantial number of infections. A research study inadvertently discovered that a clinic rapid HIV testing process was failing to detect cases of established (high antibody titer) infection, exhibiting an estimated 68.7% sensitivity (95% CI [41.3%-89.0%]) over the course of the first three weeks of observation. The setting is a public service clinic that provides STI diagnosis and treatment in an impoverished, peri urban community outside of Cape Town, South Africa. METHODS: The researchers and local health administrators collaborated to investigate the cause of the poor test performance and make necessary corrections. The clinic changed the brand of rapid test being used and later introduced quality improvement measures. Observations were made of the clinic staff as they administered rapid HIV tests to real patients. Estimated testing sensitivity was calculated as the number of rapid HIV test positive individuals detected by the clinic divided by this number plus the number of PCR positive, highly reactive 3rd generation ELISA patients identified among those who were rapid test negative at the clinic. RESULTS: In the period of five months after the clinic made the switch of rapid HIV tests, estimated sensitivity improved to 93.5% (95% CI [86.5%-97.6%]), during which time observations of counselors administering tests at the clinic found poor adherence to the recommended testing protocol. Quality improvement measures were implemented and estimated sensitivity rose to 95.1% (95% CI [83.5%-99.4%]) during the final two months of full observation. CONCLUSIONS: Poor testing procedure in the field can lead to exceedingly low levels of rapid HIV test sensitivity, making it imperative that stringent quality control measures are implemented where they do not already exist. Certain brands of rapid-testing kits may perform better than others when faced with sub-optimal use. PMID- 20307309 TI - Frequent CXCR4 tropism of HIV-1 subtype A and CRF02_AG during late-stage disease- indication of an evolving epidemic in West Africa. AB - BACKGROUND: HIV-1 is one of the fastest evolving pathogens, and is distinguished by geographic and genetic variants that have been classified into different subtypes and circulating recombinant forms (CRFs). Early in infection the primary coreceptor is CCR5, but during disease course CXCR4-using HIV-1 populations may emerge. This has been correlated with accelerated disease progression in HIV-1 subtype B. Basic knowledge of HIV-1 coreceptor tropism is important due to the recent introduction of coreceptor antagonists in antiretroviral therapy, and subtype-specific differences regarding how frequently HIV-1 CXCR4-using populations appear in late-stage disease need to be further investigated. To study how frequently CXCR4-using populations appear in late-stage disease among HIV-1 subtype A and CRF02_AG, we evaluated the accuracy of a recombinant virus phenotypic assay for these subtypes, and used it to determine the HIV-1 coreceptor tropism of plasma samples collected during late-stage disease in Guinea-Bissau. We also performed a genotypic analysis and investigated subtype specific differences in the appearance of CXCR4 tropism late in disease. RESULTS: We found that the recombinant virus phenotypic assay accurately predicted HIV-1 coreceptor tropism of subtype A and CRF02_AG. Over the study period (1997-2007), we found an increasing and generally high frequency of CXCR4 tropism (86%) in CRF02_AG. By sequence analysis of the V3 region of our samples we developed a novel genotypic rule for predicting CXCR4 tropism in CRF02_AG, based on the combined criteria of the total number of charged amino acids and net charge. This rule had higher sensitivity than previously described genotypic rules and may be useful for development of future genotypic tools for this CRF. Finally, we conducted a literature analysis, combining data of 498 individuals in late-stage disease, and found high amounts of CXCR4 tropism for all major HIV-1 subtypes (60 77%), except for subtype C (15%). CONCLUSIONS: The increase in CXCR4 tropism over time suggests an evolving epidemic of CRF02_AG. The results of the literature analysis demonstrate the need for further studies investigating subtype-specific emergence for CXCR4-tropism; this may be particularly important due to the introduction of CCR5-antagonists in HIV treatment regimens. PMID- 20307311 TI - Primary medical care in Irish prisons. AB - BACKGROUND: An industrial dispute between prison doctors and the Irish Prison Service (IPS) took place in 2004. Part of the resolution of that dispute was that an independent review of prison medical and support services be carried out by a University Department of Primary Care. The review took place in 2008 and we report here on the principal findings of that review. METHODS: This study utilised a mixed methods approach. An independent expert medical evaluator (one of the authors, DT) inspected the medical facilities, equipment and relevant custodial areas in eleven of the fourteen prisons within the IPS. Semistructured interviews took place with personnel who had operational responsibility for delivery of prison medical care. Prison doctors completed a questionnaire to elicit issues such as allocation of clinician's time, nurse and administrative support and resources available. RESULTS: There was wide variation in the standard of medical facilities and infrastructure provided across the IPS. The range of medical equipment available was generally below that of the equivalent general practice scheme in the community. There is inequality within the system with regard to the ratio of doctor-contracted time relative to the size of the prison population. There is limited administrative support, with the majority of prisons not having a medical secretary. There are few psychiatric or counselling sessions available. CONCLUSIONS: People in prison have a wide range of medical care needs and there is evidence to suggest that these needs are being met inconsistently in Irish prisons. PMID- 20307312 TI - Accuracy of DXA in estimating body composition changes in elite athletes using a four compartment model as the reference method. AB - BACKGROUND: Dual-energy x-ray absorptiometry (DXA) provides an affordable and practical assessment of multiple whole body and regional body composition. However, little information is available on the assessment of changes in body composition in top-level athletes using DXA. The present study aimed to assess the accuracy of DXA in tracking body composition changes (relative fat mass [%FM], absolute fat mass [FM], and fat-free mass [FFM]) of elite male judo athletes from a period of weight stability to prior to a competition, compared to a four compartment model (4C model), as the criterion method. METHODS: A total of 27 elite male judo athletes (age, 22.2 +/- 2.8 yrs) athletes were evaluated. Measures of body volume by air displacement plethysmography, bone mineral content assessed by DXA, and total-body water assessed by deuterium dilution were used in a 4C model. Statistical analyses included examination of the coefficient of determinant (r2), standard error of estimation (SEE), slope, intercept, and agreement between models. RESULTS: At a group level analysis, changes in %FM, FM, and FFM estimates by DXA were not significantly different from those by the 4C model. Though the regression between DXA and the 4C model did not differ from the line of identity DXA %FM, FM, and FFM changes only explained 29%, 36%, and 38% of the 4C reference values, respectively. Individual results showed that the 95% limits of agreement were -3.7 to 5.3 for %FM, -2.6 to 3.7 for FM, and -3.7 to 2.7 for FFM. The relation between the difference and the mean of the methods indicated a significant trend for %FM and FM changes with DXA overestimating at the lower ends and underestimating at the upper ends of FM changes. CONCLUSIONS: Our data indicate that both at group and individual levels DXA did not present an expected accuracy in tracking changes in adiposity in elite male judo athletes. PMID- 20307313 TI - Effects of body weight and alcohol consumption on insulin sensitivity. AB - BACKGROUND: Obesity is a risk factor for the development of insulin resistance, which can eventually lead to type-2 diabetes. Alcohol consumption is a protective factor against insulin resistance, and thus protects against the development of type-2 diabetes. The mechanism by which alcohol protects against the development of type-2 diabetes is not well known. To determine the mechanism by which alcohol improves insulin sensitivity, we fed water or alcohol to lean, control, and obese mice. The aim of this study was to determine whether alcohol consumption and body weights affect overlapping metabolic pathways and to identify specific target genes that are regulated in these pathways. METHOD: Adipose tissue dysfunction has been associated with the development of type-2 diabetes. We assessed possible gene expression alterations in epididymal white adipose tissue (WAT). We obtained WAT from mice fed a calorie restricted (CR), low fat (LF Control) or high fat (HF) diets and either water or 20% ethanol in the drinking water. We screened the expression of genes related to the regulation of energy homeostasis and insulin regulation using a gene array composed of 384 genes. RESULTS: Obesity induced insulin resistance and calorie restriction and alcohol improved insulin sensitivity. The insulin resistance in obese mice was associated with the increased expression of inflammatory markers Cd68, Il-6 and Il-1alpha; in contrast, most of these genes were down-regulated in CR mice. Anti-inflammatory factors such as Il-10 and adrenergic beta receptor kinase 1 (Adrbk1) were decreased in obese mice and increased by CR and alcohol. Also, we report a direct correlation between body weight and the expression of the following genes: Kcnj11 (potassium inwardly-rectifying channel, subfamily J, member 11), Lpin2 (lipin2), and Dusp9 (dual-specificity MAP kinase phosphatase 9). CONCLUSION: We show that alcohol consumption increased insulin sensitivity. Additionally, alterations in insulin sensitivity related with obesity were coupled with alterations in inflammatory genes. We provide evidence that alcohol may improve insulin sensitivity by up-regulating anti-inflammatory genes. Moreover, we have indentified potential gene targets in energy metabolic pathways and signal transducers that may contribute to obesity-related insulin resistance as well as calorie restriction and alcohol-induced insulin sensitivity. PMID- 20307314 TI - Use of microarray technology to assess the time course of liver stress response after confinement exposure in gilthead sea bream (Sparus aurata L.). AB - BACKGROUND: Selection programs for growth and stress traits in cultured fish are fundamental to the improvement of aquaculture production. The gilthead sea bream (Sparus aurata) is the main aquacultured species in the Mediterranean area and there is considerable interest in the genetic improvement of this species. With the aim of increasing the genomic resources in gilthead sea bream and identifying genes and mechanisms underlying the physiology of the stress response, we developed a cDNA microarray for gilthead sea bream that is enriched by suppression substractive hybridization with stress and immunorelevant genes. This microarray is used to analyze the dynamics of gilthead sea bream liver expression profile after confinement exposure. RESULTS: Groups of confined and control juvenile fish were sampled at 6, 24, 72 and 120 h post exposure. GeneSpring analyses identified 202 annotated genes that appeared differentially expressed at least at one sampling time (P < 0.05). Gene expression results were validated by quantitative PCR of 10 target genes, and K-means clustering of differently expressed genes identified four major temporal gene expression profiles. Set 1 encompassed a rapid metabolic readjustment with enhanced uptake and intracellular transport of fatty acids as metabolic fuels. Set 2 was associated with a wide variety of tissue repair and remodeling processes that were mostly mediated by the stress response of the endoplasmic reticulum (ER). Sets 3 and 4 encompassed the re-establishment of cellular homeostasis with increased intracellular trafficking and scavenging of reactive oxygen species (ROS), accompanied by a bidirectional regulation of the immune system and a general decline of ROS production. CONCLUSIONS: Collectively, these findings show the complex nature of the adaptive stress response with a clear indication that the ER is an important control point for homeostatic adjustments. The study also identifies metabolic pathways which could be analyzed in greater detail to provide new insights regarding the transcriptional regulation of the stress response in fish. PMID- 20307315 TI - Genome-scale metabolic analysis of Clostridium thermocellum for bioethanol production. AB - BACKGROUND: Microorganisms possess diverse metabolic capabilities that can potentially be leveraged for efficient production of biofuels. Clostridium thermocellum (ATCC 27405) is a thermophilic anaerobe that is both cellulolytic and ethanologenic, meaning that it can directly use the plant sugar, cellulose, and biochemically convert it to ethanol. A major challenge in using microorganisms for chemical production is the need to modify the organism to increase production efficiency. The process of properly engineering an organism is typically arduous. RESULTS: Here we present a genome-scale model of C. thermocellum metabolism, iSR432, for the purpose of establishing a computational tool to study the metabolic network of C. thermocellum and facilitate efforts to engineer C. thermocellum for biofuel production. The model consists of 577 reactions involving 525 intracellular metabolites, 432 genes, and a proteomic based representation of a cellulosome. The process of constructing this metabolic model led to suggested annotation refinements for 27 genes and identification of areas of metabolism requiring further study. The accuracy of the iSR432 model was tested using experimental growth and by-product secretion data for growth on cellobiose and fructose. Analysis using this model captures the relationship between the reduction-oxidation state of the cell and ethanol secretion and allowed for prediction of gene deletions and environmental conditions that would increase ethanol production. CONCLUSIONS: By incorporating genomic sequence data, network topology, and experimental measurements of enzyme activities and metabolite fluxes, we have generated a model that is reasonably accurate at predicting the cellular phenotype of C. thermocellum and establish a strong foundation for rational strain design. In addition, we are able to draw some important conclusions regarding the underlying metabolic mechanisms for observed behaviors of C. thermocellum and highlight remaining gaps in the existing genome annotations. PMID- 20307316 TI - Up- and down-modulation of liver cytochrome P450 activities and associated events in two murine malaria models. AB - BACKGROUND: The mechanisms by which malaria up and down-regulates CYP activities are not understood yet. It is also unclear whether CYP activities are modulated during non-lethal malaria infections. This study was undertaken to evaluate the time course of CYP alterations in lethal (Plasmodium berghei ANKA) and non-lethal (Plasmodium chabaudi chabaudi) murine malaria. Additionally, hypotheses on the association of CYP depression with enhanced nitric oxide (NO) production, and of CYP2a5 induction with endoplasmic reticulum dysfunction, enhanced haem metabolism and oxidative stress were examined as well. METHODS: Female DBA-2 and C57BL/6 mice were infected with P.berghei ANKA or P. chabaudi and killed at different post-infection days. Infection was monitored by parasitaemia rates and clinical signs. NO levels were measured in the serum. Activities of CYP1a (ethoxyresorufin O-deethylase), 2b (benzyloxyresorufin-O-debenzylase), 2a5 (coumarin-7 hydroxylase) and uridine-diphosphoglucuronyl-transferase (UGT) were determined in liver microsomes. Glutathione-S-transferase (GST) activity and concentrations of gluthatione (GSH) and thiobarbituric acid-reactive substances (TBARS) were determined in the liver. Levels of glucose-regulated protein 78 (GRP78) were evaluated by immunoblotting, while mRNAs of haemoxygenase-1 (HO-1) and inducible nitric oxide synthase (iNOS) were determined by quantitative RT-PCR. RESULTS: Plasmodium berghei depressed CYP1a and 2b and induced 2a5 in DBA-2 mice. In P.berghei-infected C57BL/6 mice CYP activities remained unaltered. In both strains, GST and UGT were not affected by P.berghei. Plasmodium c. chabaudi depressed CYP1a and 2b and induced 2a5 activities on the day of peak parasitaemia or near this day. CYP2a5 induction was associated with over-expression of HO-1 and enhanced oxidative stress, but it was not associated with GRP78 induction, a marker of endoplasmic reticulum stress. Plasmodium chabaudi increased serum NO on days near the parasitaemia peak in both strains. Although not elevating serum NO, P.berghei enhanced iNOS mRNA expression in the liver. CONCLUSION: Down-regulation of CYP1a and 2b and induction of 2a5 occurred in lethal and non-lethal infections when parasitaemia rates were high. A contribution of NO for depression of CYP2b cannot be ruled out. Results were consistent with the view that CYP2a5 and HO-1 are concurrently up-regulated and suggested that CYP2a5 induction may occur in the absence of enhanced endoplasmic reticulum stress. PMID- 20307317 TI - Evidence of perturbations of cell cycle and DNA repair pathways as a consequence of human and murine NF1-haploinsufficiency. AB - BACKGROUND: Neurofibromatosis type 1 (NF1) is a common monogenic tumor predisposition disorder that arises secondary to mutations in the tumor suppressor gene NF1. Haploinsufficiency of NF1 fosters a permissive tumorigenic environment through changes in signalling between cells, however the intracellular mechanisms for this tumor-promoting effect are less clear. Most primary human NF1+/- cells are a challenge to obtain, however lymphoblastoid cell lines (LCLs) have been collected from large NF1 kindreds. We hypothesized that the genetic effects of NF1-haploinsufficiency may be discerned by comparison of genome-wide transcriptional profiling in somatic, non-tumor cells (LCLs) from NF1 affected and -unaffected individuals. As a cross-species filter for heterogeneity, we compared the results from two human kindreds to whole-genome transcriptional profiling in spleen-derived B lymphocytes from age- and gender matched Nf1+/- and wild-type mice, and used gene set enrichment analysis (GSEA), Onto-Express, Pathway-Express and MetaCore tools to identify genes perturbed in NF1-haploinsufficiency. RESULTS: We observed moderate expression of NF1 in human LCLs and of Nf1 in CD19+ mouse B lymphocytes. Using the t test to evaluate individual transcripts, we observed modest expression differences in the transcriptome in NF1-haploinsufficient LCLs and Nf1-haploinsuffiicient mouse B lymphocytes. However, GSEA, Onto-Express, Pathway-Express and MetaCore analyses identified genes that control cell cycle, DNA replication and repair, transcription and translation, and immune response as the most perturbed in NF1 haploinsufficient conditions in both human and mouse. CONCLUSIONS: Haploinsufficiency arises when loss of one allele of a gene is sufficient to give rise to disease. Haploinsufficiency has traditionally been viewed as a passive state. Our observations of perturbed, up-regulated cell cycle and DNA repair pathways may functionally contribute to NF1-haploinsufficiency as an "active state" that ultimately promotes the loss of the wild-type allele. PMID- 20307318 TI - Effects of clusterin over-expression on metastatic progression and therapy in breast cancer. AB - BACKGROUND: Clusterin is a secreted glycoprotein that is upregulated in a variety of cell lines in response to stress, and enhances cell survival. A second nuclear isoform of clusterin that is associated with cell death has also been identified. The aim of this study was to determine the role(s) of the secretory isoform in breast tumor progression and metastasis. METHODS: To investigate the role of secretory clusterin in the biology of breast cancer tumor growth and resistance to therapy we have engineered an MCF-7 cell line (MCF-7CLU) that over-expresses clusterin. We have measured the in vitro effects of clusterin over-expression on cell cycle, cell death, and sensitivity to TNFalpha and tamoxifen. Using an orthotopic model of breast cancer, we have also determined the effects of over expression of clusterin on tumor growth and metastatic progression. RESULTS: In vitro, over-expression of secretory clusterin alters the cell cycle kinetics and decreases the rate of cell death, resulting in the enhancement of cell growth. Over-expression of secretory clusterin also blocks the TNFalpha-mediated induction of p21 and abrogates the cleavage of Bax to t-Bax, rendering the MCF 7CLU cells significantly more resistant to the cytokine than the parental cells. Orthotopic primary tumors derived from MCF-7CLU cells grow significantly more rapidly than tumors derived from parental MCF-7 cells and, unlike the parental cells, metastasize frequently to the lungs. CONCLUSIONS: These data suggest that secretory clusterin, which is frequently up-regulated in breast cancers by common therapies, including anti-estrogens, may play a significant role in tumor growth, metastatic progression and subsequent drug resistance in surviving cells. PMID- 20307319 TI - Application of support vector machine modeling for prediction of common diseases: the case of diabetes and pre-diabetes. AB - BACKGROUND: We present a potentially useful alternative approach based on support vector machine (SVM) techniques to classify persons with and without common diseases. We illustrate the method to detect persons with diabetes and pre diabetes in a cross-sectional representative sample of the U.S. population. METHODS: We used data from the 1999-2004 National Health and Nutrition Examination Survey (NHANES) to develop and validate SVM models for two classification schemes: Classification Scheme I (diagnosed or undiagnosed diabetes vs. pre-diabetes or no diabetes) and Classification Scheme II (undiagnosed diabetes or pre-diabetes vs. no diabetes). The SVM models were used to select sets of variables that would yield the best classification of individuals into these diabetes categories. RESULTS: For Classification Scheme I, the set of diabetes-related variables with the best classification performance included family history, age, race and ethnicity, weight, height, waist circumference, body mass index (BMI), and hypertension. For Classification Scheme II, two additional variables--sex and physical activity--were included. The discriminative abilities of the SVM models for Classification Schemes I and II, according to the area under the receiver operating characteristic (ROC) curve, were 83.5% and 73.2%, respectively. The web-based tool-Diabetes Classifier was developed to demonstrate a user-friendly application that allows for individual or group assessment with a configurable, user-defined threshold. CONCLUSIONS: Support vector machine modeling is a promising classification approach for detecting persons with common diseases such as diabetes and pre-diabetes in the population. This approach should be further explored in other complex diseases using common variables. PMID- 20307320 TI - The expression of TRMT2A, a novel cell cycle regulated protein, identifies a subset of breast cancer patients with HER2 over-expression that are at an increased risk of recurrence. AB - BACKGROUND: Over-expression of HER2 in a subset of breast cancers (HER2+) is associated with high histological grade and aggressive clinical course. Despite these distinctive features, the differences in response of HER2+ patients to both adjuvant cytotoxic chemotherapy and targeted therapy (e.g. trastuzumab) suggests that unrecognized biologic and clinical diversity is confounding treatment strategies. Furthermore, the small but established risk of cardiac morbidity with trastuzumab therapy compels efforts towards the identification of biomarkers that might help stratify patients. METHODS: A single institution tissue array cohort assembled at the Clearview Cancer Institute of Huntsville (CCIH) was screened by immunohistochemistry staining using a large number of novel and commercially available antibodies to identify those with a univariate association with clinical outcome in HER2+ patients. Staining with antibody directed at TRMT2A was found to be strongly associated with outcome in HER2+ patients. This association with outcome was tested in two independent validation cohorts; an existing staining dataset derived from tissue assembled at the Cleveland Clinic Foundation (CCF), and in a new retrospective study performed by staining archived paraffin blocks available at the Roswell Park Cancer Institute (RPCI). RESULTS: TRMT2A staining showed a strong correlation with likelihood of recurrence at five years in 67 HER2+ patients from the CCIH discovery cohort (HR 7.0; 95% CI 2.4 to 20.1, p < 0.0004). This association with outcome was confirmed using 75 HER2+ patients from the CCF cohort (HR 3.6; 95% CI 1.3 to 10.2, p < 0.02) and 64 patients from the RPCI cohort (HR 3.4; 95% CI 1.3-8.9, p < 0.02). In bivariable analysis the association with outcome was independent of grade, tumor size, nodal status and the administration of conventional adjuvant chemotherapy in the CCIH and RPCI cohorts. CONCLUSIONS: Studies from three independent single institution cohorts support TRMT2A protein expression as a biomarker of increased risk of recurrence in HER2+ breast cancer patients. These results suggest that TRMT2A expression should be further studied in the clinical trial setting to explore its predictive power for response to adjuvant cytotoxic chemotherapy in combination with HER2 targeted therapy. PMID- 20307321 TI - Ultrafine particles from diesel vehicle emissions at different driving cycles induce differential vascular pro-inflammatory responses: implication of chemical components and NF-kappaB signaling. AB - BACKGROUND: Epidemiological evidence supports the association between exposure to ambient particulate matter (PM) and cardiovascular diseases. Chronic exposure to ultrafine particles (UFP; Dp <100 nm) is reported to promote atherosclerosis in ApoE knockout mice. Atherogenesis-prone factors induce endothelial dysfunction that contributes to the initiation and progression of atherosclerosis. We previously demonstrated that UFP induced oxidative stress via c-Jun N-terminal Kinases (JNK) activation in endothelial cells. In this study, we investigated pro inflammatory responses of human aortic endothelial cells (HAEC) exposed to UFP emitted from a diesel truck under an idling mode (UFP1) and an urban dynamometer driving schedule (UFP2), respectively. We hypothesize that UFP1 and UFP2 with distinct chemical compositions induce differential pro-inflammatory responses in endothelial cells. RESULTS: UFP2 contained a higher level of redox active organic compounds and metals on a per PM mass basis than UFP1. While both UFP1 and UFP2 induced superoxide production and up-regulated stress response genes such as heme oxygenease-1 (HO-1), OKL38, and tissue factor (TF), only UFP2 induced the expression of pro-inflammatory genes such as IL-8 (2.8 +/- 0.3-fold), MCP-1 (3.9 +/- 0.4-fold), and VCAM (6.5 +/- 1.1-fold) (n = 3, P < 0.05). UFP2-exposed HAEC also bound to a higher number of monocytes than UFP1-exposed HAEC (Control = 70 +/- 7.5, UFP1 = 106.7 +/- 12.5, UFP2 = 137.0 +/- 8.0, n = 3, P < 0.05). Adenovirus NF-kappaB Luciferase reporter assays revealed that UFP2, but not UFP1, significantly induced NF-kappaB activities. NF-kappaB inhibitor, CAY10512, significantly abrogated UFP2-induced pro-inflammatory gene expression and monocyte binding. CONCLUSION: While UFP1 induced higher level of oxidative stress and stress response gene expression, only UFP2, with higher levels of redox active organic compounds and metals, induced pro-inflammatory responses via NF kappaB signaling. Thus, UFP with distinct chemical compositions caused differential response patterns in endothelial cells. PMID- 20307322 TI - Elevated osteoprotegerin is associated with abnormal ankle brachial indices in patients infected with HIV: a cross-sectional study. AB - BACKGROUND: Patients infected with HIV have an increased risk for accelerated atherosclerosis. Elevated levels of osteoprotegerin, an inflammatory cytokine receptor, have been associated with a high incidence of cardiovascular disease (including peripheral arterial disease, or PAD), acute coronary syndrome, and cardiovascular mortality. The objective of this study was to determine whether PAD is prevalent in an HIV-infected population, and to identify an association with HIV-specific and traditional cardiovascular risk factors, as well as levels of osteoprotegerin. METHODS: One hundred and two patients infected with HIV were recruited in a cross-sectional study. To identify the prevalence of PAD, ankle brachial indices (ABIs) were measured. Four standard ABI categories were utilized: < or = 0.90 (definite PAD); 0.91-0.99 (borderline); 1.00-1.30 (normal); and >1.30 (high). Medical history and laboratory measurements were obtained to determine possible risk factors associated with PAD in HIV-infected patients. RESULTS: The prevalence of PAD (ABI < or = 0.90) in a young HIV-infected population (mean age: 48 years) was 11%. Traditional cardiovascular risk factors, including advanced age and previous cardiovascular history, as well as elevated C reactive protein levels, were associated with PAD. Compared with patients with normal ABIs, patients with high ABIs had significantly elevated levels of osteoprotegerin [1428.9 (713.1) pg/ml vs. 3088.6 (3565.9) pg/ml, respectively, p = 0.03]. CONCLUSIONS: There is a high prevalence of PAD in young HIV-infected patients. A number of traditional cardiovascular risk factors and increased osteoprotegerin concentrations are associated with abnormal ABIs. Thus, early screening and aggressive medical management for PAD may be warranted in HIV infected patients. PMID- 20307323 TI - Intensity level for exercise training in fibromyalgia by using mathematical models. AB - BACKGROUND: It has not been assessed before whether mathematical models described in the literature for prescriptions of exercise can be used for fibromyalgia syndrome patients. The objective of this paper was to determine how age-predicted heart rate formulas can be used with fibromyalgia syndrome populations as well as to find out which mathematical models are more accurate to control exercise intensity. METHODS: A total of 60 women aged 18-65 years with fibromyalgia syndrome were included; 32 were randomized to walking training at anaerobic threshold. Age-predicted formulas to maximum heart rate ("220 minus age" and "208 minus 0.7 x age") were correlated with achieved maximum heart rate (HRMax) obtained by spiroergometry. Subsequently, six mathematical models using heart rate reserve (HRR) and age-predicted HRMax formulas were studied to estimate the intensity level of exercise training corresponding to heart rate at anaerobic threshold (HRAT) obtained by spiroergometry. Linear and nonlinear regression models were used for correlations and residues analysis for the adequacy of the models. RESULTS: Age-predicted HRMax and HRAT formulas had a good correlation with achieved heart rate obtained in spiroergometry (r = 0.642; p < 0.05). For exercise prescription in the anaerobic threshold intensity, the percentages were 52.2-60.6% HRR and 75.5-80.9% HRMax. Formulas using HRR and the achieved HRMax showed better correlation. Furthermore, the percentages of HRMax and HRR were significantly higher for the trained individuals (p < 0.05). CONCLUSION: Age predicted formulas can be used for estimating HRMax and for exercise prescriptions in women with fibromyalgia syndrome. Karnoven's formula using heart rate achieved in ergometric test showed a better correlation. For the prescription of exercises in the threshold intensity, 52% to 60% HRR or 75% to 80% HRMax must be used in sedentary women with fibromyalgia syndrome and these values are higher and must be corrected for trained patients. PMID- 20307324 TI - Characterization of 13 multi-drug resistant Salmonella serovars from different broiler chickens associated with those of human isolates. AB - BACKGROUND: Salmonella are frequently isolated from chickens and their products. Prevalent serogroups and serovars of Salmonella as well as their genotypes and antibiograms were determined for cloacal samples from 1595 chickens. To understand the possible serovar and H antigens for transmission between chicken and human, serovars and their H antigens of 164 chicken and 5314 human isolates were compared. RESULTS: Prevalence of Salmonella differed among chicken lines and ages. Chicken and human isolates belonged mainly to serogroup B, C1, C2-C3, D, and E. 13 serovars and 66 serovars were identified for chicken and human isolates respectively. The common serovars for chicken and human isolates were S. Typhimurium, S. Enteritidis, S. Albany, S. Derby, and S. Anatum and shared common H1 antigens "g complex; i; e,h; and z4,z24" and H2 antigens "1 complex and -". In human isolates, H1 antigen "i" and H2 antigen "-" were common in all serogroups. In chicken, antimicrobial susceptibility differed among serogroups, serovars and three counties. All isolates were susceptible to cefazolin and ceftriaxone, but highly resistant to ampicillin, chloramphenicol, flumequine, streptomycin, sulfamethoxazole-trimethoprim, and tetracycline. Except those isolates of serogroup C1 of Chick group and serogroup G, all isolates were multi-drug resistance. Only S. Kubacha, S. Typhimurium, S. Grampian, and S. Mons were resistant to ciprofloxacin and/or enrofloxacin. CONCLUSION: In chicken, prevalent serogroups and serovars were associated with chicken ages, lines and regions; and flouroquinolone-resistant and MDR isolates emerged. H1 antigens "g complex and i" and H2 antigens "1 complex and -" might be important for transmission of Salmonella between chicken and human. PMID- 20307325 TI - Multidrug resistant yeasts in synanthropic wild birds. AB - BACKGROUND: The aim of this study was to investigate the presence of multidrug resistant yeasts in the faeces of synanthropic wild birds from the Bangsar suburb of Kuala Lumpur. METHODS: Species characterisations of yeast isolates and determinations of antimycotic susceptibility profiles were undertaken using the commercial characterization kit, Integral System Yeasts Plus (Liofilchem, Italy). RESULTS: Fourteen species of yeasts were detected in the bird faecal samples.Candida albicans was present in 28.89% of bird faecal samples, Candida krusei (13.33%), Candida tropicalis (4.44%), Candida glabrata (4.44%), Candida parapsilosis (2.22%), Candida lambica (2.22%), Candida stellatoidea (2.22%), Candida rugosa (2.22%) and Candida lusitaniae (2.22%). Amongst the non-candidal yeast isolates, Cryptococcus laurentii was present in 6.67% of bird faecal samples, Cryptococcus uniguttulatus (4.44%), Saccharomyces cerevisiae (4.44%), Trichosporon pullulans (2.22%), Trichosporon pullulans/Cryptococcus albidus (8.89%) and Rhodotorula rubra/Rhodotorula glutinis (4.44%). Of the isolated yeasts, 18.1% (or 26/144) were found to be resistant to all 11 antimycotic agents they were tested against i.e. Nystatin, Amphotericin B, Flucytosine, Econazole, Ketoconazole, Clotrimazole, Miconazole, Itraconazole, Voriconazole, Fluconazole 16 and Fluconazole 64. 45.8% (or 66/144) of the bird faecal yeast isolates were resistant to four or more of the 11 antimycotic agents they were tested against. CONCLUSIONS: This finding is of public health significance as these synanthropic wild birds may be reservoirs for transmission of drug resistant yeast infections to humans. PMID- 20307326 TI - Oligonucleotide microarray for the identification of potential mycotoxigenic fungi. AB - BACKGROUND: Mycotoxins are secondary metabolites which are produced by numerous fungi and pose a continuous challenge to the safety and quality of food commodities in South Africa. These toxins have toxicologically relevant effects on humans and animals that eat contaminated foods. In this study, a diagnostic DNA microarray was developed for the identification of the most common food-borne fungi, as well as the genes leading to toxin production. RESULTS: A total of 40 potentially mycotoxigenic fungi isolated from different food commodities, as well as the genes that are involved in the mycotoxin synthetic pathways, were analyzed. For fungal identification, oligonucleotide probes were designed by exploiting the sequence variations of the elongation factor 1-alpha (EF-1 alpha) coding regions and the internal transcribed spacer (ITS) regions of the rRNA gene cassette. For the detection of fungi able to produce mycotoxins, oligonucleotide probes directed towards genes leading to toxin production from different fungal strains were identified in data available in the public domain. The probes selected for fungal identification and the probes specific for toxin producing genes were spotted onto microarray slides. CONCLUSIONS: The diagnostic microarray developed can be used to identify single pure strains or cultures of potentially mycotoxigenic fungi as well as genes leading to toxin production in both laboratory samples and maize-derived foods offering an interesting potential for microbiological laboratories. PMID- 20307327 TI - Prevalence and risk profile of cervical Human papillomavirus infection in Zhejiang Province, southeast China: a population-based study. AB - BACKGROUND: Benign or malignant lesions caused by Human papillomavirus (HPV) produce considerable health burden worldwide. Since limited cross-protection would be offered between HPV types, heterogeneity in HPV type-specific distribution should be taken into account when predicting the effect of current prophylactic vaccines and forming the basic for the second-generation vaccines targeted to specific regions. Here, we investigated the prevalence of cervical HPV infection, as well as predictors concerned, in Zhejiang Province, southeast China. RESULTS: Totally 4987 cervical samples from five randomly chosen counties in Zhejiang Province were detected. The overall HPV prevalence was 13.3%. Established high-risk (HR) HPV prevalence was 10.2%. HPV-52 was the most prevalent type (3.1%), followed by HPV-16 (2.5%), -58 (2.1%), -68 (1.0%) and -81 (0.9%). HPV-16 or -18 were present in 3.1% of the detected samples, while 174 specimens (3.5%) were positive for any of HPV-6, -11, -16 and -18. The prevalence of HPV vaccine types was consistently low across age groups. Bimodal age distribution in HR-HPV, including established HR and probably HR-HPV, was observed, with a clear second peak in perimenopausal women. Multivariate unconditional logistic regression models revealed that partner's lifetime number of partners was the only common independent predictor of overall, established HR, established low-risk, single-type and multiple-type HPV infection in current study. CONCLUSIONS: We have observed low prevalence of HPV vaccine types and relatively high prevalence of HPV-52 and -58 in our population. Our findings support universal "catch-up" vaccination of sexual experienced young women in Zhejiang Province, as well as enhance the hypothesis that the second-generation HPV prophylactic vaccines including HPV-52 and -58 may offer higher protection for women in China and other Asian areas. Furthermore, our data support close surveillance of perimenopausal women with HR-HPV infection. PMID- 20307328 TI - The autonomic nervous system dysregulation in response to orthostatic stress in children with neurocardiogenic syncope. AB - Neurocardiogenic syncope is a common disorder, which is considered as a benign condition. However, sudden loss of conscience and muscle tone causes anxiety among the family members due to its similarity to sudden death. Autonomic nervous system dysregulation is thought to be responsible in the aetiology. Heart rate variability is used for assessment of autonomic nervous system.We evaluated 24 children between 6 and 18 years (mean plus or minus standard deviation is equal to 12.5 plus or minus 3.28, with neurocardiogenic syncope and 10 healthy controls, mean plus or minus standard deviation is equal to 12.48 plus or minus 3.27) by using 24 hour Holter monitorisation and head-up tilt test. Heart rate variability analysis was performed using the Holter recordings obtained both during head-up tilt test and throughout the day.Our results revealed that, there is no significant difference between the study and the control groups in terms of the mean heart rate and all indices of the heart rate variability (p > 0.05). However, during the first 5 minutes of the head-up tilt test, standard deviation of all RR intervals and root mean square of successive differences were significantly lower in the syncope group compared with the control group, 42.17 plus or minus 12.56 versus 60.10 plus or minus 33.10 and 21.26 plus or minus 8.87 versus 36.80 plus or minus 31.03; p-values 0.02 and 0.03, respectively.In conclusion; autonomic functions in children with neurocardiogenic syncope are similar to healthy children. However, sympathetic hyperactivation occurs during the early phase of orthostatic stress in children with neurocardiogenic syncope comparing to healthy controls. Parasympathetic innervation is not sufficient in compensation of this sympathetic hyperactivation. Management strategy in neurocardiogenic syncope should be based on these pathophysiologic mechanisms. PMID- 20307329 TI - Abnormalities of the major intrathoracic arteries in Turner syndrome as revealed by magnetic resonance imaging. AB - BACKGROUND: Ectatic aortopathy and arterial abnormalities cause excess morbidity and mortality in Turner syndrome, where a state of vasculopathy seemingly extends into the major head and neck branch arteries. OBJECTIVE: We investigated the prevalence of abnormalities of the major intrathoracic arteries, their interaction with arterial dimensions, and their association with karyotype. DESIGN: Magnetic resonance imaging scans determined the arterial abnormalities as well as head and neck branch artery and aortic dimensions in 99 adult women with Turner syndrome compared with 33 healthy female controls. Echocardiography determined aortic valve morphology. RESULTS: In Turner syndrome, the relative risk of any congenital abnormality was 7.7 (p = 0.003) and 6.7 of ascending aortic dilation (p = 0.02). A bovine aortic arch was seen in both Turner syndrome and controls. Other abnormalities were only encountered in Turner syndrome: elongated transverse aortic arch (47%), bicuspid aortic valve (27%), aortic coarctation (13%), aberrant right subclavian artery (8%), and aortic arch hypoplasia (2%). The innominate and left common carotid arteries were enlarged in Turner syndrome (p < 0.001). Significant associations were first, bicuspid aortic valve with aortic coarctation, elongated transverse aortic arch, and ascending aortic dilation; second, aortic coarctation with elongated aortic arch and descending aortic dilation; third, 45,X with aortic coarctation, elongated transverse aortic arch and ascending aortic dilation; and fourth, branch artery dilation with bicuspid aortic valve, aortic coarctation, elongated transverse aortic arch and 45,X. CONCLUSION: An increased risk of arterial abnormalities, aortic dilation, and enlargement of the branch arteries was found in Turner syndrome without distinct patterns of co-segregation. PMID- 20307330 TI - Critical care outcomes in pulmonary atresia and intact ventricular septum undergoing single-ventricle palliation. AB - OBJECTIVE: To examine early outcomes for pulmonary atresia with intact ventricular septum undergoing single-ventricle palliation and to determine risk factors for mortality. DESIGN: Retrospective observational study. SETTING: Tertiary paediatric critical care unit. INTERVENTION: Risk factors for mortality were sought for infants after the primary intervention whether surgical shunt or ductal stent. MEASUREMENTS AND MAIN RESULTS: We reviewed outcomes of 19 infants with pulmonary atresia with intact ventricular septum undergoing single-ventricle palliation between July, 2000 and July, 2008. Echocardiograms, cardiac catheterisation findings, anaesthesia, and critical care management, as well as autopsy reports were reviewed. We modelled survival after surgery and looked for predictors of early mortality. A total of 19 infants underwent single-ventricle palliation and seven of these died. The risk of death was increased by a lower arterial pH at induction of anaesthesia (p = 0.01), a lower systolic blood pressure (p = 0.01), and technical problems during surgery (p = 0.03). On admission to the critical care unit, a lower mixed venous saturation (p = 0.02) and presence of tachyarrhythmia (p = 0.02) were associated with the need for mechanical support within the first 48 hours. CONCLUSIONS: There is a high early mortality for those who undergo single-ventricle palliation. It is higher for those who are haemodynamically compromised before surgery; technical problems, and haemodynamic instability during surgery also increase mortality. PMID- 20307331 TI - Paul Raymond Lurie: an innovator and founder of paediatric cardiology. PMID- 20307332 TI - Non-compacted myocardium and foetal left isomerism as a hydrops' aetiology. AB - We present a case report of a pregnant woman with increased risk for trisomy 21 at first-trimester screening, assessed by ultrasonography, that was sent to our hospital. Amniocentesis was performed at 14 weeks and 2 days to obtain foetal karyotype that was normal (46,XX). At 19 weeks and 1 day, foetal hydrops associated with cardiac malformation was detected by routine scan. Foetal echocardiogram revealed a complete auriculoventricular septal defect, non compacted myocardium, and a bradycardia of 70-90 beats per minute, which lead to the suspicion of left isomerism. Foetal death occurred at 20 weeks and 3 days. Autopsy was consistent with the prenatal diagnosis. PMID- 20307333 TI - Successful transseptal puncture for radiofrequency ablation of left atrial tachycardia after closure of secundum atrial septal defect with Amplatzer septal occluder. AB - We report on a 37-year-old woman presenting with atrial arrhythmias after catheter closure of a secundum atrial septal defect with an Amplatzer septal occluder device. Electrophysiological studies suggested that the arrhythmia originated from the left atrium, from an area near the device. Transseptal puncture was successfully performed under transoesophageal guidance and the arrhythmia was successfully ablated. This case showed that transseptal puncture can be safely performed in the presence of an Amplatzer septal occluder device under transoesophageal echocardiography guidance and we speculate that the device may have created the substrate for the arrhythmia. PMID- 20307334 TI - Giant coronary aneurysms developed in a child of Kawasaki disease with only 3 days of fever. AB - Prolonged fever, 5 days or more, is the cardinal feature of Kawasaki disease. We described a 5-year-old boy with initial presentations of fever, conjunctivitis, and strawberry tongue. The fever only lasted for 3 days. However, giant coronary aneurysms developed later. This patient reminds us that coronary complications could happen even the fever is less than 5 days. Criteria of fever duration might need reconsideration. PMID- 20307335 TI - Evaluation of paediatric cardiosurgical model in Croatia by using the Aristotle basic complexity score and the risk adjustment for congenital cardiac surgery-1 method. AB - OBJECTIVE: The Aristotle basic complexity score and the risk adjustment in congenital cardiac surgery-1 method were developed and used to compare outcomes of congenital cardiac surgery. Both methods were used to compare results of procedures performed on our patients in Croatian cardiosurgical centres and results of procedures were taken abroad. METHODS: The study population consisted of all patients with congenital cardiac disease born to Croatian residents between 1 October, 2002 and 1 October, 2007 undergoing a cardiovascular operation during this period. RESULTS: Of the 556 operations, the Aristotle basic complexity score could be assigned to 553 operations and the risk adjustment in congenital cardiac surgery-1 method to 536 operations. Procedures were performed in two institutions in Croatia and seven institutions abroad. The average complexity for cardiac procedures performed in Croatia was significantly lower. With both systems, along with the increase in complexity, there is also an increase in mortality before discharge and postoperative length of stay. Only after the adjustment for complexity there are marked differences in mortality and occurrence of postoperative complications. CONCLUSION: Both, the Aristotle basic complexity score and the risk adjustment in congenital cardiac surgery-1 method were predictive of in-hospital mortality as well as prolonged postoperative length to stay, and can be used as a tool in our country to evaluate a cardiosurgical model and recognise potential problems. PMID- 20307336 TI - Woven right and aneurysmatic left coronary artery associated with Kawasaki disease in a 9-month-old patient. AB - Woven coronary artery disease is an extremely rare congenital abnormality with unusual findings of branching thin channels and distal reanastomosis. This pathologic finding was reported earlier in a few adult patients. In Kawasaki disease, coronary arterial system is commonly affected, which causes a necessity of cardiac imaging. We report a 9-month-old infant with Kawasaki disease in which left coronary artery aneurysm and woven right coronary artery were coincidentally detected during coronary angiography. After 1 year, coronary angiogram was re performed and showed no changes in the coronary arteries. During the follow-up period of 4 years, the patient remained asymptomatic. In Kawasaki disease, there is a tendency for thrombus formation and a woven coronary artery can be easily misinterpreted as a thrombus. Woven coronary artery is a benign condition and it should not be confused with a thrombus or a stenosis related finding which needs a medical or surgical intervention. PMID- 20307337 TI - Progressively worsening hypertrophic cardiomyopathy in a child with newly diagnosed Costello syndrome while receiving growth hormone therapy. AB - We describe a 6-year-old boy with newly diagnosed Costello syndrome after the diagnosis of severe hypertrophic cardiomyopathy. His neonatal asymmetric septal cardiomyopathy resolved by 9 months of age but reappeared at 6 years of age. This report highlights two important concepts: the association of genetic syndromes with hypertrophic cardiomyopathy and the possibility of worsening severity of hypertrophic cardiomyopathy linked to growth hormone therapy. PMID- 20307338 TI - Congenital cardiovascular lesions in children with trisomy 21 at the Bustamante Hospital for Children. AB - OBJECTIVE: To describe the cardiac lesions seen in children with trisomy 21, the outcome of these children and rates of access to corrective surgery at the Bustamante Hospital for Children. METHODS: A 10-year retrospective review of the records of trisomy 21 patients with cardiac lesions referred to the Bustamante Hospital for Children was conducted. RESULTS: A total of 76 patients were enrolled in the study, 30 (40%) males and 46 (60%) females; among these 110 cardiac lesions were detected. A total of 20 (26%) patients died, 48 (63%) survived, and for 8 (11%) the status was unknown. The most common lesion was the atrioventricular septal defect, which accounted for 41 (37%) of all the lesions and occurred as a single defect in 24 (53%) patients. At presentation, 33 (46%) patients had one or more medical complication; 30 (91%) had cardiac failure, 10 (30%) had pneumonia and 5 (15%) had evidence of systemic pulmonary arterial pressures. Cardiac catheterisation was recommended for 43 (56%) patients but only 10 (23%) had the procedure done. Surgery was recommended for 60 (79%) patients; of these 6 (10%) patients had the procedure done. The median time of survival was 88 months (7.3 years). The age of presentation was not found to significantly affect outcome. CONCLUSION: Trisomy 21 patients with cardiac lesions have high morbidity and mortality. This morbidity and mortality could be reduced if surgical intervention was offered routinely. PMID- 20307339 TI - Population-based surveillance study of Campylobacter infections in Finland. AB - The annual incidence in 14,361 campylobacteriosis cases reported in Finland in 2002-2005 varied between 61 and 76/100,000 population. The mean incidence was highest (148/100,000) in the 25-29 years age group and lowest (range 21 24/100,000) in children aged 5-14 years and patients aged >=75 years. The number of domestic cases was low in winter and peaked in summer. A total of 622 strains isolated from domestic infections and 785 foreign travel-related strains were serotyped. Serotypes Pen 3 and Pen 37 had the strongest association with travel related infections (96%, P<0.001), and Pen 6,7, Pen 12 and Pen 27 were significantly associated with domestic infections (>70% domestic within each serotype, P<0.001). Pen 2 and Pen 1,44 were less common in older than in younger patients. Of domestic strains, a higher proportion of Pen 2 strains was isolated in winter (18%) compared to the other serotypes (0-10%). PMID- 20307340 TI - Age, influenza pandemics and disease dynamics. AB - The world is currently confronting the first influenza pandemic of the 21st century [caused by a novel pandemic influenza A (H1N1) virus]. Earlier pandemics have been characterized by age distributions that are distinct from those observed with seasonal influenza epidemics, with higher attack rates (and correspondingly increased proportionate or relative mortality) in younger individuals. While the genesis of protection against infection in older individuals during a pandemic is uncertain, differential vulnerability to infection by age has important implications for disease dynamics and control, and for choice of optimal vaccination strategies. Age-related vulnerability to infection may explain differences between school- and community-derived estimates of the reproductive number (R) for a newly emerged pandemic strain, and may also help explain the failure of a newly emerged influenza A (H1N1) virus strain to cause a pandemic in 1977. Age-related factors may also help explain variability in attack rates, and the size and impact of influenza epidemics across jurisdictions and between populations. In Canada, such effects have been observed in the apparently increased severity of outbreaks on Indigenous peoples' reserves. The implications of these patterns for vaccine allocation necessitate targeted research to understand age-related vulnerabilities early in an influenza pandemic. PMID- 20307341 TI - Diarrhoea morbidity and mortality in older children, adolescents, and adults. AB - Diarrhoea is a leading cause of morbidity and mortality yet diarrhoea specific incidence and mortality rates for older children, adolescents, and adults have not been systematically calculated for many countries. We conducted a systematic literature review to generate regional incidence rates by age and to summarize diarrhoea specific mortality rates for regions of the world with inadequate vital registration data. Diarrhoea morbidity rates range from 29.9 episodes/100 person years for adults in the South East Asian region to 88.4 episodes/100 person-years in older children in the Eastern Mediterranean region and have remained unchanged in the last 30 years. Diarrhoea mortality rates decline as the child ages and remain relatively constant during adulthood. These data are critical for improving estimates worldwide and further highlight the need for improved diarrhoea specific morbidity and mortality data in these age groups. PMID- 20307342 TI - An assessment of the antibacterial activity in larval excretion/secretion of four species of insects recorded in association with corpses, using Lucilia sericata Meigen as the marker species. AB - The relative antibacterial activities of excretion/secretion (ES) from two carrion-feeding insects, Calliphora vicina Robineau-Desvoidy and Dermestes maculatus DeGeer, and a detritivore, Tenebrio molitor Linnaeus, were compared to that of Lucilia sericata Meigen, a species with ES of known antibacterial capacity, in order to explore the antimicrobial potential of other carrion and detritivore species. Viable counts were used to assess time-kill of ES against five bacterial species, Staphylococcus aureus, Escherichia coli, Bacillus cereus, Pseudomonas aeruginosa and Proteus mirabilis. Antibacterial activity was recorded in all four insect species although T. molitor and D. maculatus were the most effective in controlling growth of P. mirabilis. The blowflies were more effective in controlling a wider range of both Gram-positive and Gram-negative bacteria. The larval ES from all species was shown to reduce bacterial growth rate although differences in antibacterial spectrum were noted and the degree of potency varied between the four species. These differences may be explained ecologically by the different colonisation times of each insect species on the corpse. Overall, this study demonstrates that research into other carrion-feeding insect species has potential to provide an increased source of antimicrobial chemicals to broaden the range of bacterial species beyond that currently controlled using L. sericata. PMID- 20307343 TI - Chemical cues from the coffee berry borer influence the locomotory behaviour of its bethylid parasitoids. AB - Cephalonomia stephanoderis and Prorops nasuta are two bethylid wasps released into several Latin American countries for classical biological control of coffee berry borer, Hypothenemus hampei, the most serious insect pest of coffee worldwide. Recent studies on the host location behaviour of these parasitoids have shown that females of both species are attracted to volatile compounds released by immature stages and dust and frass of H. hampei. In this study, we investigated the role of the contact chemicals present in dust and frass of H. hampei on the behaviour of P. nasuta and C. stephanoderis females. Parasitoids remained longer on patches treated with methanol extracts than on acetone and hexane extracts. Females spent more time on the patch treated with the methanol extract of dust and frass than on the patches treated with the methanol extract of dry coffee and methanol control. The concentration of the methanol extracts from dust and frass influenced the locomotory activity of parasitoids of both species. The time that females spent in the patch tended to increase as the concentration of the methanol extracts increased. A further experiment aimed to identify other behavioural descriptors and gain a deeper understanding of the mechanisms underlying the response of parasitoids to methanol extracts was performed. Females of both species spent more time, covered more distance, turned more (per unit time and per unit distance), and decreased their speed when they contacted patches treated with methanol extracts in comparison to patches treated with methanol control. PMID- 20307344 TI - Words in puddles of sound: modelling psycholinguistic effects in speech segmentation. AB - There are numerous models of how speech segmentation may proceed in infants acquiring their first language. We present a framework for considering the relative merits and limitations of these various approaches. We then present a model of speech segmentation that aims to reveal important sources of information for speech segmentation, and to capture psycholinguistic constraints on children's language perception. The model constructs a lexicon based on information about utterance boundaries and deduces phonotactic constraints from the discovered lexicon. Compared to other models of speech segmentation, our model performs well in terms of accuracy, computational tractability and the number of components of the model. Finally, our model also reflects the psycholinguistic effects of language learning, in terms of the early advantage for segmentation provided by the child's name, and by revealing the overlap in usefulness of information for segmentation and for grammatical categorization of the language. PMID- 20307345 TI - Segmenting words from natural speech: subsegmental variation in segmental cues. AB - Most computational models of word segmentation are trained and tested on transcripts of speech, rather than the speech itself, and assume that speech is converted into a sequence of symbols prior to word segmentation. We present a way of representing speech corpora that avoids this assumption, and preserves acoustic variation present in speech. We use this new representation to re evaluate a key computational model of word segmentation. One finding is that high levels of phonetic variability degrade the model's performance. While robustness to phonetic variability may be intrinsically valuable, this finding needs to be complemented by parallel studies of the actual abilities of children to segment phonetically variable speech. PMID- 20307346 TI - Modeling the contribution of phonotactic cues to the problem of word segmentation. AB - How do infants find the words in the speech stream? Computational models help us understand this feat by revealing the advantages and disadvantages of different strategies that infants might use. Here, we outline a computational model of word segmentation that aims both to incorporate cues proposed by language acquisition researchers and to establish the contributions different cues can make to word segmentation. We present experimental results from modified versions of Venkataraman's (2001) segmentation model that examine the utility of: (1) language-universal phonotactic cues; (2) language-specific phonotactic cues which must be learned while segmenting utterances; and (3) their combination. We show that the language-specific cue improves segmentation performance overall, but the language-universal phonotactic cue does not, and that their combination results in the most improvement. Not only does this suggest that language-specific constraints can be learned simultaneously with speech segmentation, but it is also consistent with experimental research that shows that there are multiple phonotactic cues helpful to segmentation (e.g. Mattys, Jusczyk, Luce & Morgan, 1999; Mattys & Jusczyk, 2001). This result also compares favorably to other segmentation models (e.g. Brent, 1999; Fleck, 2008; Goldwater, 2007; Johnson & Goldwater, 2009; Venkataraman, 2001) and has implications for how infants learn to segment. PMID- 20307347 TI - Implicational markedness and frequency in constraint-based computational models of phonological learning. AB - This study examines the interacting roles of implicational markedness and frequency from the joint perspectives of formal linguistic theory, phonological acquisition and computational modeling. The hypothesis that child grammars are rankings of universal constraints, as in Optimality Theory (Prince & Smolensky, 1993/2004), that learning involves a gradual transition from an unmarked initial state to the target grammar, and that order of acquisition is guided by frequency, along the lines of Levelt, Schiller & Levelt (2000), is investigated. The study reviews empirical findings on syllable structure acquisition in Dutch, German, French and English, and presents novel findings on Polish. These comparisons reveal that, to the extent allowed by implicational markedness universals, frequency covaries with acquisition order across languages. From the computational perspective, the paper shows that interacting roles of markedness and frequency in a class of constraint-based phonological learning models embody this hypothesis, and their predictions are illustrated via computational simulation. PMID- 20307348 TI - Different digestion of caprine whey proteins by human and porcine gastrointestinal enzymes. AB - The objective of the present study was twofold: first to compare the degradation patterns of caprine whey proteins digested with either human digestive juices (gastric or duodenal) or commercial porcine enzymes (pepsin or pancreatic enzymes) and second to observe the effect of gastric pH on digestion. An in vitro two-step assay was performed at 37 degrees C to simulate digestion in the stomach (pH 2, 4 or 6) and the duodenum (pH 8). The whey proteins were degraded more efficiently by porcine pepsin than by human gastric juice at all pH values. Irrespective of the enzyme source, gastric digestion at pH 2 followed by duodenal digestion resulted in the most efficient degradation. Lactoferrin, serum albumin and the Ig heavy chains were highly degraded with less than 6 % remaining after digestion. About 15, 56 and 50 % Ig light chains, beta-lactoglobulin (beta-LG) and alpha-lactalbumin remained intact, respectively, when digested with porcine enzymes compared with 25, 74 and 81 % with human digestive juices. For comparison, purified bovine beta-LG was digested and the peptide profiles obtained were compared with those of the caprine beta-LG in the digested whey. The bovine beta-LG seemed to be more extensively cleaved than the caprine beta-LG in the whey. Commercial enzymes appear to digest whey proteins more efficiently compared with human digestive juices when used at similar enzyme activities. This could lead to conflicting results when comparing human in vivo protein digestion with digestion using purified enzymes of non-human species. Consequently the use of human digestive juices might be preferred. PMID- 20307349 TI - Establishment and characterization of embryonic stem-like cells from porcine somatic cell nuclear transfer blastocysts. AB - This study was aimed to establish embryonic stem (ES)-like cells from blastocysts derived from somatic cell nuclear transfer (SCNT) in pig. Somatic cells isolated from both day-30 fetus and neonatal cloned piglet were used for donor cells. A total of 60 blastocysts (46 and 14 derived from fetal and neonatal fibroblast donor cells, respectively) were seeded onto a mitotically inactive mouse embryonic fibroblast (MEF) monolayer and two ES-like cell lines, one from each donor cell type, were established. They remained undifferentiated over more than 52 (fetal fibroblast-derived) and 48 (neonatal fibroblast-derived) passages, while retaining alkaline phosphatase activity and reactivity with ES specific markers Oct-4, stage-specific embryonic antigen-1 (SSEA-1), SSEA-4, TRA-1-60 and TRA-1-81. These ES-like cells maintained normal diploid karyotype throughout subculture and successfully differentiated into embryoid bodies that expressed three germ layer-specific genes (ectoderm: beta-III tubulin; endoderm: amylase; and mesoderm: enolase) after culture in leukemia inhibitory factor-free medium. Microsatellite analysis confirmed that they were genetically identical to its donor cells. Combined with gene targeting, our results may contribute to developing an efficient method for producing transgenic pigs for various purposes. PMID- 20307350 TI - Effects of fish oil and starch added to a diet containing sunflower-seed oil on dairy goat performance, milk fatty acid composition and in vivo delta9 desaturation of [13C]vaccenic acid. AB - The potential benefits on human health have prompted an interest in developing nutritional strategies for specifically increasing rumenic acid (RA) in ruminant milk. The aims of the present study were to (i) compare two dietary treatments with lipid supplements on milk yield and composition, (ii) measure the in vivo delta9-desaturation of vaccenic acid (VA) to RA using 13C-labelled VA and (iii) determine the effect of the dietary treatments on this variable. Treatments were 90 g sunflower-seed oil (SO) per d or 60 g sunflower-seed oil and 30 g fish oil per d plus additional starch (SFO), in a grassland hay-based diet given to eight Alpine goats in a 2 x 2 cross-over design with 21 d experimental periods. Milk yield and composition were similar between treatments. Goats fed SFO had higher milk 6 : 0-16 : 0 concentration, lower milk sigmaC18 concentrations and showed no effect on milk VA and RA, compared with SO. At the end of the experiment, intravenous injection of 1.5 g [13C]VA followed by measurements of milk lipid 13C enrichment showed that in vivo 31.7 and 31.6 % of VA was delta9-desaturated into milk RA in the caprine with the SO and SFO treatments, respectively. The expression of genes encoding for delta9-desaturase (or stearoyl-CoA desaturase; SCD1, SCD5) in mammary tissues and four milk delta9-desaturation ratios were similar between treatments. In conclusion, the present study provides the first estimates of in vivo endogenous synthesis of RA (63-73 % of milk RA) from VA in goats, and shows no difference between the two lipid supplements compared. PMID- 20307351 TI - Effect of incremental amounts of fish oil in the diet on ruminal lipid metabolism in growing steers. AB - Based on the potential benefits to human health, there is interest in developing sustainable nutritional strategies to enhance the concentration of long-chain n-3 fatty acids in ruminant-derived foods. Four Aberdeen Angus steers fitted with rumen and duodenal cannulae were used in a 4 x 4 Latin square experiment with 21 d experimental periods to examine the potential of fish oil (FO) in the diet to enhance the supply of 20 : 5n-3 and 22 : 6n-3 available for absorption in growing cattle. Treatments consisted of total mixed rations based on maize silage fed at a rate of 85 g DM/kg live weight 0.75/d containing 0, 8, 16 and 24 g FO/kg diet DM. Supplements of FO reduced linearly (P < 0.01) DM intake and shifted (P < 0.01) rumen fermentation towards propionate at the expense of acetate and butyrate. FO in the diet enhanced linearly (P < 0.05) the flow of trans-16 : 1, trans-18 : 1, trans-18 : 2, 20 : 5n-3 and 22 : 6n-3, and decreased linearly (P < 0.05) 18 : 0 and 18 : 3n-3 at the duodenum. Increases in the flow of trans-18 : 1 were isomer dependent and were determined primarily by higher amounts of trans-11 reaching the duodenum. In conclusion, FO alters ruminal lipid metabolism of growing cattle in a dose-dependent manner consistent with an inhibition of ruminal biohydrogenation, and enhances the amount of long-chain n-3 fatty acids at the duodenum, but the increases are marginal due to extensive biohydrogenation in the rumen. PMID- 20307352 TI - The influence of maternal glycaemia and dietary glycaemic index on pregnancy outcome in healthy mothers. AB - Infant birth weight has increased in Ireland in recent years along with levels of childhood overweight and obesity. The present article reviews the current literature on maternal glycaemia and the role of the dietary glycaemic index (GI) and its impact on pregnancy outcomes. It is known that maternal weight and weight gain significantly influence infant birth weight. Fetal macrosomia (birth weight >4000 g) is associated with an increased risk of perinatal trauma to both mother and infant. Furthermore, macrosomic infants have greater risk of being obese in childhood, adolescence and adulthood compared to normal-sized infants. There is evidence that there is a direct relationship between maternal blood glucose levels during pregnancy and fetal growth and size at birth, even when maternal blood glucose levels are within their normal range. Thus, maintaining blood glucose concentrations within normal parameters during pregnancy may reduce the incidence of fetal macrosomia. Maternal diet, and particularly its carbohydrate (CHO) type and content, influences maternal blood glucose concentrations. However, different CHO foods produce different glycaemic responses. The GI was conceived by Jenkins in 1981 as a method for assessing the glycaemic responses of different CHO. Data from clinical studies in healthy pregnant women have documented that consuming a low-GI diet during pregnancy reduces peaks in postprandial glucose levels and normalises infant birth weight. Pregnancy is a physiological condition where the GI may be of particular relevance as glucose is the primary fuel for fetal growth. PMID- 20307353 TI - Markers of cardiovascular risk are not changed by increased whole-grain intake: the WHOLEheart study, a randomised, controlled dietary intervention. AB - Recommendations for whole-grain (WG) intake are based on observational studies showing that higher WG consumption is associated with reduced CVD risk. No large scale, randomised, controlled dietary intervention studies have investigated the effects on CVD risk markers of substituting WG in place of refined grains in the diets of non-WG consumers. A total of 316 participants (aged 18-65 years; BMI>25 kg/m2) consuming < 30 g WG/d were randomly assigned to three groups: control (no dietary change), intervention 1 (60 g WG/d for 16 weeks) and intervention 2 (60 g WG/d for 8 weeks followed by 120 g WG/d for 8 weeks). Markers of CVD risk, measured at 0 (baseline), 8 and 16 weeks, were: BMI, percentage body fat, waist circumference; fasting plasma lipid profile, glucose and insulin; and indicators of inflammatory, coagulation, and endothelial function. Differences between study groups were compared using a random intercepts model with time and WG intake as factors. Although reported WG intake was significantly increased among intervention groups, and demonstrated good participant compliance, there were no significant differences in any markers of CVD risk between groups. A period of 4 months may be insufficient to change the lifelong disease trajectory associated with CVD. The lack of impact of increasing WG consumption on CVD risk markers implies that public health messages may need to be clarified to consider the source of WG and/or other diet and lifestyle factors linked to the benefits of whole-grain consumption seen in observational studies. PMID- 20307354 TI - Linseed oil in the maternal diet increases long chain-PUFA status of the foetus and the newborn during the suckling period in pigs. AB - Linseed oil, being rich in 18 : 3n-3, represents an alternative source of n-3 PUFA in the maternal diet. However, little is known about the effect of this oil on the long chain n-3 PUFA composition of offspring, which are required for normal growth and maturation of numerous organs. The main objective of the experiment was therefore to investigate fatty acid composition of tissues from sows at the end of gestation and from piglets during the first week of postnatal life in response to maternal dietary linseed oil intake. Sows received either a lard (LAR)-based diet or a linseed oil (LSO)-based diet during gestation and lactation. Fatty acid composition was evaluated in sow plasma, placenta and milk, and in different tissues of piglets on days 0, 3, 7, 21 and 32. The LSO diet increased the proportions of n-3 PUFA and especially 22 : 6n-3 in the placenta. The carcass of LSO piglets at birth contained greater proportions of 20 : 5n-3, 22 : 5n-3 and 22 : 6n-3. The LSO sow milk exhibited greater proportions of 18 : 3n-3 compared with the LAR sow milk. The piglets suckling LSO sows had greater proportions of 18 : 3n-3, 20 : 5n-3 and 22 : 5n-3 in plasma and carcass. The proportions of 22 : 5n-3 and 22 : 6n-3 were greater in the brain of LSO piglets than in that of LAR piglets during the suckling period. In conclusion, LSO in the maternal diet during gestation and lactation increases 22 : 6n-3 concentrations in the placenta and in the foetus carcass, and it maintains 22 : 6n-3 concentrations in the brain during the first week of postnatal life. PMID- 20307355 TI - Effects of an acute alpha-lactalbumin manipulation on mood and food hedonics in high- and low-trait anxiety individuals. AB - Serotonergic hypofunction is associated with a depressive mood state, an increased drive to eat and preference for sweet (SW) foods. High-trait anxiety individuals are characterised by a functional shortage of serotonin during stress, which in turn increases their susceptibility to experience a negative mood and an increased drive for SW foods. The present study examined whether an acute dietary manipulation, intended to increase circulating serotonin levels, alleviated the detrimental effects of a stress-inducing task on subjective appetite and mood sensations, and preference for SW foods in high-trait anxiety individuals. Thirteen high- (eleven females and two males; anxiety scores 45.5 (sd 5.9); BMI 22.9 (sd 3.0)kg/m(2)) and twelve low- (ten females and two males; anxiety scores 30.4 (sd 4.8); BMI 23.4 (sd 2.5) kg/m(2)) trait anxiety individuals participated in a placebo-controlled, two-way crossover design. Participants were provided with 40 g alpha-lactalbumin (LAC; l-tryptophan (Trp):large neutral amino acids (LNAA) ratio of 7.6) and 40 g casein (placebo) (Trp:LNAA ratio of 4.0) in the form of a snack and lunch on two test days. On both the test days, participants completed a stress-inducing task 2 h after the lunch. Mood and appetite were assessed using visual analogue scales. Changes in food hedonics for different taste and nutrient combinations were assessed using a computer task. The results demonstrated that the LAC manipulation did not exert any immediate effects on mood or appetite. However, LAC did have an effect on food hedonics in individuals with high-trait anxiety after acute stress. These individuals expressed a lower liking (P = 0.012) and SW food preference (P = 0.014) after the stressful task when supplemented with LAC. PMID- 20307356 TI - Heat shock protein 70 and cellular disturbances in cochlear cisplatin ototoxicity model. AB - BACKGROUND: Exposure to cisplatin leads to cochlear cell death by apoptosis; these changes are most marked on the seventh day after exposure. Heat shock proteins are induced in inner ear cells in response to a variety of stimuli. This study examined the role of heat shock protein 70 in cisplatin-induced cochlear cell death. METHODS: Fifty-six Sprague-Dawley rats were involved. Some were injected with cisplatin (5 mg/kg body weight), some with cisplatin plus the caspase inhibitor Z-Asp(OMe)-Glu(OMe)-Val-Asp(OME)-fluoromethylketone (5 mg/kg body weight) and others were left as controls (being injected only with saline). Seven days later, we examined the expression of heat shock protein 70 and several other apoptosis-related proteins within the rat cochlear cells; we also assessed total superoxide dismutase activity, auditory brainstem response and auditory steady state response. RESULTS: Seven days after cisplatin injection, significantly increased expression of heat shock protein 70 was found within the rat cochleae. This correlated with increased executioner caspase levels, total superoxide dismutase activity and auditory brainstem response thresholds, and a significant elevation in auditory steady state response thresholds. Inhibition of caspase-3 activity significantly reduced cochlear heat shock protein 70 expression and total superoxide dismutase activity, and improved auditory brainstem response and auditory steady state response thresholds. CONCLUSIONS: Seven days after cisplatin exposure, we found disturbances of the cochlear cellular machinery involving heat shock protein 70, other apoptotic proteins and total superoxide dismutase. PMID- 20307357 TI - Anxiety and depression in head and neck out-patients. AB - OBJECTIVES: To investigate the prevalence of psychological distress in head and neck out-patients. DESIGN: We used the Hospital Anxiety and Depression Scale to screen 106 patients for mood disorders in a London head and neck ENT out-patient clinic. SETTING: Queen's Hospital, Romford, UK. PARTICIPANTS: One hundred and six patients attending a head and neck out-patient clinic. MAIN OUTCOME MEASURE: Hospital Anxiety and Depression Scale score. RESULTS: Approximately 39 per cent of patients had a possible anxiety disorder (10 per cent were rated as severe), and 27 per cent had possible depression (10 per cent were rated as severe). CONCLUSION: We recommend that a member of the head and neck multidisciplinary team should be trained to identify and correctly refer psychologically distressed patients to appropriate existing psychiatric services. PMID- 20307358 TI - Disability and quality of life among community elderly with dizziness: report from the Ibadan study of ageing. AB - BACKGROUND: Dizziness is prevalent among the elderly. However, little is known about its impact on quality of life and disability, especially in developing countries, where the number of elderly people is increasing. AIM: This study aimed to determine the prevalence of disability, and the quality of life, among elderly persons with dizziness living in the community. SETTING AND DESIGN: Longitudinal cohort study of dizziness among elderly persons (i.e. aged 65 years and over) residing in Yoruba-speaking areas of Nigeria. METHOD: Face-to-face interviews with respondents selected using a multi-stage, stratified area probability sampling of households. Dizziness was based on self-reporting and health-related quality of life was measured using the brief version of the World Health Organization quality of life assessment. RESULT: Dizziness was reported and confirmed in 318/1281 elderly respondents, a prevalence of 24.8 per cent. Respondents comprised 197 (61.9 per cent) women and 121 (38.1 per cent) men. Thirty-nine respondents (12.3 per cent) were aged 65-69 years, 91 (28.6 per cent) 70-74 years, 66 (20.8 per cent) 75-79 years and 122 (38.4 per cent) > or =80 years. The prevalence of disability in activities of daily living was 29.56 per cent, and that of disability in instrumental activities of daily living 10.1 per cent. The influence of gender was not significant. The prevalence of disability in activities of daily living (p = 0.00) and in instrumental activities of daily living (p = 0.00) increased significantly with age. Univariate analysis revealed that disability in activities of daily living (p = 0.00), disability in instrumental activities of daily living (p = 0.01), poor family interaction (p = 0.00), poor community involvement (p = 0.00), overall poor health (p = 0.00), current depression (p = 0.01), and difficulty with sedentary (p = 0.00) and vigorous (p = 0.00) activities were significantly more common among elderly respondents with dizziness, compared with non-dizzy elderly respondents. In contrast, cognitive impairment (p = 0.05) was not significantly correlated. The probabilities of the occurrence of difficulty with vigorous or sedentary mobility in our elderly respondents were 2.6 and 1.9, respectively, compared with non dizzy elderly respondents. Similarly, the probabilities of the occurrence of disability in activities of daily living, current depression and dementia were 1.6 each. Logistic regression analyses for age, sex, medical conditions and presence of disability confirmed that dizziness was significantly associated with worsened cognition. Similarly, dizziness was significantly associated with reduced total quality of life (p = 0.00), and also with reductions in the physical (p = 0.00), psychological (p = 0.00) and environmental (p = 0.00) domains of the research instrument. CONCLUSION: Among elderly people with dizziness, there was a high prevalence of significant disability requiring assistance. In addition, dizziness alone significantly reduced these individual's overall total quality of life, and their quality of life as regards physical, psychological and environmental parameters. This information will assist policy planning for the elderly. PMID- 20307359 TI - Citrobacter freundii causing pharyngitis and secondary retropharyngeal abscess with intrathoracic extension to the diaphragm: minimally invasive management of a rare case. AB - INTRODUCTION: Citrobacter freundii is a rare but potentially aggressive cause of pharyngitis which may progress to retropharyngeal abscess with diaphragmatic extension. OBJECTIVE: To raise awareness of: (1) citrobacter as a potential cause of head and neck infection, including retropharyngeal abscess; (2) a novel surgical approach to draining such an abscess; and (3) citrobacter's particular biological properties which may affect the clinical course. METHOD: Case report. RESULTS: The abscess was drained via a minimally invasive posterior pharyngeal wall incision and placement of a suction catheter into the mediastinum through this incision. Residual intrathoracic collections were drained by the cardiothoracic team via percutaneous aspiration. The patient made a full recovery. CONCLUSION: Early recognition of citrobacter head and neck infections, an awareness of the peculiarities of the clinical course of such infections, and timely surgical intervention can prevent catastrophic outcomes. A minimally invasive approach to mediastinal collections can be considered as a viable alternative to open thoracotomy, which carries a high morbidity rate. PMID- 20307360 TI - Management of carcinoma showing thymus-like element. AB - OBJECTIVE: To consolidate the key features of carcinoma showing thymus-like element, including its management. METHOD: We present our experience of the difficult diagnosis and management of this rare tumour. We also present the results of an extensive literature search, documenting those aspects of the clinical picture, natural history and management of carcinoma showing thymus-like element which are relevant to head and neck surgeons. RESULT: Intrathyroidal, epithelial carcinoma showing thymus-like element is a rare, malignant tumour of the thyroid gland, with histopathological features similar to squamous cell carcinoma but a more favourable prognosis. It is usually treated surgically using a combination of total thyroidectomy and selective neck dissection, with radiotherapy and chemotherapy in selected cases. CONCLUSION: Carcinoma showing thymus-like element of the thyroid gland is a rare condition. Head and neck surgeons with a thyroid interest should be aware of this tumour, because of its close histological resemblance to other, commoner malignancies of the thyroid gland. PMID- 20307361 TI - Communicating terminal diagnoses to Hispanic patients. AB - OBJECTIVE: This study addressed factors physicians employ in their communication of a terminal diagnosis and a hospice referral to Hispanic patients. METHOD: The research method used was an exploratory qualitative in-depth semi-structured interview with thematic analysis. The interviews were with ten physicians in Central Florida. The interviews were conducted in Spanish and/or English with physicians who serve terminally ill Hispanic patients. RESULTS: The findings provide vital information on factors that impact communication of diagnosis and hospice referral. Themes emerged relating to role of family members and end-of life decision-making. Language barriers and limited knowledge of cultural factors and beliefs impacted communication related to end-of-life decisions. Gaps in training and education for physicians were also identified. SIGNIFICANCE OF RESULTS: These results suggest that discussing end-of-life issues with the diverse category of Hispanic patients and families will be enhanced by eliminating language barriers, increased understanding of the role of family members, and knowledge of cultural factors and beliefs related to end-of-life decisions. PMID- 20307362 TI - Characteristics, interventions, and outcomes of misdiagnosed delirium in cancer patients. AB - OBJECTIVE: Although delirium is a common psychiatric complication in cancer patients, it is often not accurately recognized. To date, the characteristics and outcome of misrecognized patients are unclear in the cancer setting. This retrospective study was planned to determine the recognition by oncologists at the psychiatric consultation, characteristics, reversibility and outcome of misrecognized patients with delirium. METHOD: We reviewed charts of 60 patients diagnosed with delirium by the psycho-oncologists who were referred to the psychiatric consultation by the oncologists. Information about demographics, initial assessment by the oncologists, delirium subtype, precipitating factors, intervention for delirium, reversibility, and final status was obtained. RESULTS: Twenty-two among 60 delirious patients were misrecognized by the oncologists at the time of consultation. They were often diagnosed as having anxiety or other psychiatric disorders. Misrecognized participants were significantly younger than accurately recognized cases of delirium. The psychiatrists made suggestions to the oncologists for all the referred patients, even when they were accurately diagnosed with delirium before consultation. For the correctly recognized patients, the main suggestion was pharmacological reevaluation. For the misdiagnosed cases, the psychiatrists suggested a reconsideration of the strategy for cancer treatment and the provision of information to the patient's family members about their condition. SIGNIFICANCE OF RESULTS: Despite its high prevalence, delirium is difficult to diagnose for non-psychiatric physicians. Its detection is important not only to give the best treatment option to cancer patients but also to provide the best opportunity to inform their family about their condition and end-of-life issues. PMID- 20307363 TI - The recognition and documentation of delirium in hospital palliative care inpatients. AB - OBJECTIVE: Delirium is a clinical syndrome that is known to be under recognized by palliative care teams. A wide variation in reported prevalence may reflect differences in definitions and assessment methods, patient characteristics, and study design. The aim of this study was to test an intervention to improve recognition of delirium in the inpatient palliative care setting. METHOD: We conducted a retrospective palliative care notes review of documented prevalence of delirium among 61 patients referred to the Specialist Palliative Care Advisory Team (SPCT). Subsequently, training in the use of the Confusion Assessment Method (CAM) was provided to the SPCT and a prospective survey of the prevalence of delirium measured by the CAM was undertaken with the next 59 patients referred. RESULTS: In the retrospective chart review, the term "delirium" was not used, and synonyms were identified and used to establish a delirium prevalence of 11.5%. In the intervention utilizing the CAM in a prospective sample of 59 referred patients, a prevalence rate of 8.5-15.2% for delirium was found. Use of the CAM was received favorably by the SPCT. SIGNIFICANCE OF RESULTS: The institution of the use of the CAM as a screening and assessment tool in the inpatient palliative care setting did not significantly increase the recognition of delirium. Reasons for the low prevalence of delirium are discussed. PMID- 20307364 TI - The significance of fatigue in relatives of palliative patients. AB - OBJECTIVE: The aim of this study was to explore the significance of fatigue among relatives of palliative patients. METHOD: This pilot study has a descriptive and cross-sectional design and is the report of four open-ended questions focusing on the relatives' experiences of fatigue. The study population consisted of relatives of patients who were cared for in palliative care settings either at home or in an institution in Uppsala County during a specific day. RESULTS: The relatives were very tired and identified worries, uncertainty, the patient's suffering, and many demands as the causes for the fatigue. The most obvious consequences of the tiredness were a lack of motivation, feelings of insufficiency and apathy, and putting their own interests aside. Many relatives expressed that having the company of close family members, taking exercise and spending time outdoors gave them strength to carry on. The health care system could make the situation easier for relatives of patients in palliative care by providing good care for the patient, and psychosocial support and respite care for the relatives. SIGNIFICANCE OF RESULTS: The result of the pilot study is only preliminary, but it showed that relatives caring for patients in a late palliative phase suffer from great fatigue and require more attention, both scientifically and in the clinical settings. PMID- 20307365 TI - Results of a pilot investigation into a complex intervention for breathlessness in advanced chronic obstructive pulmonary disease (COPD): brief report. AB - OBJECTIVE: Breathlessness is the most common devastating symptom of advanced chronic obstructive pulmonary disease (COPD). The Breathlessness Intervention Service (BIS) is a multidisciplinary service that uses both pharmacological and non-pharmacological evidence-based interventions to reduce the impact of the symptom. The results of a Phase II evaluation of the service are reported. METHOD: Pretest - posttest analysis of non-randomized data was performed for 13 patients with severe advanced COPD referred to BIS. RESULTS: Mean VAS-Distress scores (primary outcome measure) decreased (improved) for the group between baseline and follow up suggesting a clinically significant improvement: 6.88 (SD = 2.50) to 5.25 (SD = 2.99). At an individual level, 11 of the 13 patients showed a decrease in their distress due to breathlessness, and for eight of these this was clinically significant (range of all decreases 0.3-7.1 cm). Changes in secondary outcome measures are also reported. SIGNIFICANCE OF RESULTS: The Breathlessness Intervention Service appears to reduce distress due to breathlessness among patients with advanced COPD. A Phase III fully-powered randomized controlled trial is warranted. PMID- 20307366 TI - Emerging adulthood and cancer: how unmet needs vary with time-since-treatment. AB - OBJECTIVE: The impact of a cancer experience during emerging adulthood (18-25 years of age) is an under-studied phenomenon, with research on young people typically focussing on children or adolescents. Needs-based research on this population is even scarcer. This study sought to ascertain the most commonly unmet needs of emerging adults with cancer, in various stages of time-since treatment, and to investigate links to psychological functioning. METHOD: Using an earlier version of a needs-based questionnaire, presently under development, as well as additional items developed specifically for this age group, the ten most unmet needs were determined for 63 emerging adults in each of the following three groups: those on or within one year since treatment; those between one and five years since treatment; and those beyond five years since treatment. Psychological functioning was measured by the Depression, Anxiety and Stress Scales (DASS-21). RESULTS: On average, participants rated 17.7 of the 132 needs as unmet. The 10 most unmet needs for each group generated a distinct picture of how needs change as time-since-treatment increases. For those at or within one year since treatment, there were a number of unmet needs directly related to health care provision and the hospital experience. For those whose treatment was more than one year previous, the most unmet needs were more focussed on emotional/psychological issues, particularly related to survivorship and life direction. Positive correlations were found between the number of unmet needs and levels of anxiety and stress. SIGNIFICANCE OF RESULTS: The results of the present study provide quantitative needs-based information about emerging adults with cancer, in the context of their treatment situation. This enables health care providers to better support the emerging adult with cancer in ways that are age appropriate and time-sensitive. The persisting levels of unmet needs and psychological distress beyond five years since treatment underscore the importance of long-term follow-up and support. PMID- 20307367 TI - Hospice volunteer as patient advocate: a trait approach. AB - OBJECTIVE: The purpose of this study is to examine traits of hospice volunteers that facilitate their success in this informal caregiving role, with the larger goal of alleviating the family caregiver burden and providing additional support to the hospice patient. To achieve this goal, a new scale was developed to tap into how hospice volunteers view their patient advocacy role. METHOD: Participants were 136 trained hospice volunteers from the Midwest who had direct contact with hospice patients. Volunteers mailed anonymous surveys that included measures of argumentativeness, locus of control, attitudes toward patient advocacy, and key demographic items. A new scale was developed to measure patient advocacy by hospice volunteers called the Hospice Volunteer as Patient Advocate. RESULTS: Submitting this scale to exploratory factor analysis, two factors emerged: duty as patient advocate and support of patient rights. After performing a multiple regression analysis, results showed that female volunteers who were high in internal locus of control were more likely to perceive that volunteers have a duty as patient advocates. Younger volunteers with more years of volunteer experience, higher levels of internal locus of control, and lower external locus of control were more likely to support patient rights. SIGNIFICANCE OF RESULTS: The findings of this study could be used to formalize hospice volunteers' role as patient advocates, thus better utilizing them as committed, caring communicators and improving patient-centered care at end-of-life. PMID- 20307368 TI - Influences on place of death in Botswana. AB - OBJECTIVE: There is an emerging body of research aimed at understanding the determinants of place of death, as where people die may influence the quality of their death. However, little is known about place of death for people of Southern Africa. This study describes place of death (home or hospital) and potential influencing factors (cause of death, age, gender, occupation, and district of residence). METHOD: We collected the death records for years 2005 and 2006 for all adult non-traumatic deaths that occurred in Botswana, described them, and looked for associations using bivariate and multivariate analyses. RESULTS: The evaluable sample consisted of 18,869 death records. Home deaths accounted for 36% of all deaths, and were predominantly listed with "unknown" cause (82.3%). Causes of death for hospital deaths were HIV/AIDS (49.7%), cardiovascular disease (13.8%), and cancer (6.6%). The mean age at the time of all deaths was 53.2 years (SD = 20.9); with 61 years (SD = 22.5) for home deaths and 48.8 years (SD = 18.6) for hospital deaths (p < .001). Logistic regression analysis revealed the following independent predictors of dying at home: unknown cause of death; female gender; >80 years of age; and residing in a city or rural area (p < .05). SIGNIFICANCE OF RESULTS: A major limitation of this study was documentation of cause of death; the majority of people who died at home were listed with an unknown cause of death. This finding impeded the ability of the study to determine whether cause of death influenced dying at home. Future study is needed to determine whether verbal autopsies would increase death-certificate listings of causes of home deaths. These data would help direct end-of-life care for patients in the home. PMID- 20307369 TI - On the road again: patient perspectives on commuting for palliative care. AB - OBJECTIVE: The aim of this research project was to gain an understanding of the experiences of rural cancer patients who commute to an urban cancer center for palliative care. METHOD: The study utilized a mixed method design. Fifteen individuals with a palliative designation participated in semi-structured interviews and filled out the Problems and Needs in Palliative Care Questionnaire. RESULTS: Qualitative findings included three major themes: cultures of rural life and care, strategies for commuting, and the effects of commuting. Participants valued their rural lifestyles and gained significant support from their communities. Strategies included preparing for the trip with particular attention to pain management, making the most of time, and maintaining significant relationships. Establishing a routine helped to offset the anxiety of commuting. Commuting was costly but the quality of life and supportive relationships obtained through treatment were significant benefits. Questionnaire data suggested that participants were experiencing a number of problems but few indicated they desired more professional attention to those problems. SIGNIFICANCE OF RESULTS: Rural lifestyles are often an important part of overall well-being and commuting for care is both costly and complex. Health care providers should assist individuals to weigh the relative contributions of staying in their rural locale versus commuting for care to their overall quality of life. Palliative-care individuals in this study indicated a number of ongoing problems but were not inclined to seek further assistance from health care providers in addressing those problems. Clinicians should actively inquire about problems and further research is needed to understand why patients are reluctant to seek help. PMID- 20307370 TI - How might Levinas' concept of the other's priority and Derrida's unconditional hospitality contribute to the philosophy of the modern hospice movement? AB - Hospitality is commonly referred as one of the meanings of hospes, the Latin word which is also the root of hospice. This article explores the semantics of the word hospice - the seal of identity of modern hospice movement - and attempts to integrate the meaning of hospitality into the modern hospice movement, understood as unconditional reception. Therefore, the article analyzes the concept of unconditional hospitality, developed by Jacques Derrida and that of ethical responsibility proposed by Emmanuel Levinas based on the phenomenological experience of the other. From this point of view, these two concepts tie in with the meaning of hospice, bringing substantial grounding elements to the hospice movement for the construction of a protective ethos. PMID- 20307371 TI - Surgical intensive care unit (ICU) delirium: a "psychosomatic" problem? AB - OBJECTIVE: Intensive Care Unit (ICU) delirium is a common complication after major surgery and related among other potential medical precipitants to either pre-existing cognitive impairment or the intensity and length of anesthesiology or the type of surgery. Nevertheless, in some rare situations, an organic etiology is not always found, which can be frustrating for the medical team. Some clinicians working in an intensive care unit have a reluctance to seek another hypothesis in the psychological field. METHOD: To illustrate this, we report the case of a 59-year-old woman who developed a massive delirium during her intensive care unit stay after being operated on for a left retroperitoneal sarcoma. Interestingly, she had had no previous cognitive disorders and a somatic explanation for her psychiatric disorder could not been found. Just before the surgery, she was grieving the recent loss of a colleague of the same age, and also a close friend, and therefore had a death anxiety. RESULTS: With this case report, we would like to point out the importance of psychological factors that might precipitate delirium in a predominately somatic environment such as an intensive care unit. SIGNIFICANCE OF RESULTS: ICU delirium can sometimes be considered as a "psychosomatic" problem with either a stress response syndrome after surgery or a defense mechanism against death anxiety. Clinicians should be aware of the possibility of such psychological factors even if they always must first rule out potential somatic causes for delirium and encourage thorough investigation and treatment of these medical causes. A collaboration with the psycho-oncologist is recommended to better manage this "psychosomatic" problem. PMID- 20307372 TI - Childhood trauma, attachment style, and a couple's experience of terminal cancer: case study. AB - OBJECTIVE: The primary objective of this article is to elucidate the significance of psychosocial distress and risk in a sub-population of end-stage cancer patients and their spouse caregivers who present with an especially challenging attachment style and histories of childhood trauma. The case study presented highlights the need to both identify and offer an empirically validated couple based intervention, along with a multi-disciplinary team approach over the trajectory of the illness and at end of life. METHOD: A validated marital protocol (emotionally focused couple therapy [EFT]) is modified for this population and conducted by an EFT-trained psychologist as part of a pilot investigation as to the feasibility and effectiveness of EFT for the terminal cancer population. Measures of marital distress, depression, hopelessness, and attachment security are completed at baseline and subsequent intervals, as reported in another publication. Attachment insecurity and the exquisitely intimate relationship with caregiving and care receiving are underscored, given the couple's traumatic childhood history. RESULTS: The couple described herein, followed from diagnosis of metastatic disease to end of life illuminates the potential effectiveness of a modified EFT protocol, and underscores the need to both identify and intervene with a population potentially at significantly high risk for marital distress, suicidality, depression, and hopelessness. SIGNIFICANCE OF RESULTS: The benefits of a multidisciplinary team is evident as the patient's symptoms of physical distress increased toward end of life and she returned to earlier behaviors, namely suicidal ideation and an attempt to alleviate her experience of suffering. The strength of the marital bond, possibly as a result of the intervention, and the efforts of the multidisciplinary team approach, demonstrate potential to mitigate a catastrophic end of life and a complicated spousal bereavement. This case study adds to the current empirical literature in an area that is currently under-studied and under-reported. PMID- 20307374 TI - Supporting early oral language skills for English language learners in inner city preschool provision. AB - BACKGROUND: A significant number of children now enter formal education in England with reduced levels of proficiency in oral language. Children who come from disadvantaged backgrounds and who are English language learners (ELL) are at risk of limited oral language skills in English which impacts on later educational achievement. AIMS: This paper reports the development of a theoretically motivated oral language intervention, Talking Time, designed to meet the needs of preschool children with poor language skills in typical preschool provision. SAMPLE: One hundred and forty-two 4-year-old children attending three inner city preschools in a disadvantaged area of London, England. METHOD: This is a quasi-experimental intervention study comparing children exposed to Talking Time with children exposed to a contrast intervention and children receiving the statutory early years curriculum. Measures were taken of both targeted and non-targeted language and cognitive skills. RESULTS: Data were analysed for the ELL. The intervention had a significant effect on vocabulary, oral comprehension, and sentence repetition but not narrative skills. As predicted, there were no effects on the skills which were not targeted. CONCLUSIONS: Regular evidence-based oral language interactions can make significant improvements in children's oral language. There is a need to examine the efficacy of more intensive interventions to raise language skills to allow learners to access the curriculum. PMID- 20307375 TI - Causal ordering of academic self-concept and achievement: effects of type of achievement measure. AB - BACKGROUND: The relation between academic self-concept and achievement has been examined in a large number of studies. The majority of these studies have found evidence for a reciprocal effects model. However, there is an ongoing debate on how students' achievement should be measured and whether the type of achievement indicator (grades, tests, teacher ratings) affects the causal pattern found in these studies. AIMS: The study aims at clarifying how the types of achievement measures and the way they are modelled can affect the results of causal ordering studies. In that sense, the study will yield recommendations for researchers in this domain and also provide some direction for practitioners seeking ways to enhance their students' achievement and/or academic self-concept. SAMPLE: Repeated measures of academic self-concept and achievement (standardized tests and teacher ratings) were examined in a sample of 1,753 students in Grades 7, 8, 10, and 12. METHOD: Structural equation modelling was used. Several models (with different types and numbers of achievement measures) were compared. RESULTS: Only small differences were found between models using one or two indicators of achievement. All models generally supported the reciprocal effects model. However, the final model, wherein tests and teacher ratings were used as separate latent variables, showed different developmental patterns in the causal relation between academic self-concept and achievement. CONCLUSIONS: Researchers should interpret the results of causal ordering studies discerningly because the type of measure chosen as an indicator of achievement might affect the causal pattern between academic self-concept and achievement. PMID- 20307377 TI - Electrophysiological assessment of polyneuropathic involvement in rheumatoid arthritis: relationships among demographic, clinical and laboratory findings. AB - OBJECTIVES: The aims of this study were to electrophysiologically evaluate polyneuropathy in rheumatoid arthritis (RA) patients and to examine the relationships among polyneuropathy and demographic, clinical and laboratory findings. PATIENTS AND METHODS: Sixty consecutive patients (51 women and nine men) with a clinical diagnosis of RA were examined electrophysiologically for the evidence of polyneuropathy. Parameters including age, gender, subcutaneous nodules, erosions, joint deformities, laboratory parameters, duration of RA, as well as dose, duration and type of disease modifying anti-rheumatic drug (DMARD) and steroid usage were recorded. RA activity was assessed using a 28-joint disease activity score (DAS28). The functional status of patients was measured using the health assessment questionnaire (HAQ). The symptoms and signs of polyneuropathy were quantified using the neuropathy symptoms score (NSS) and the neuropathy disability score (NDS), respectively. RESULTS: Ten patients (17%, eight women and two men) had polyneuropathic involvement as defined by nerve conduction studies (NCS). Two patients had mild symmetric sensory neuropathy and eight patients had mild symmetric sensorimotor axonal polyneuropathy. There was no significant difference in age, gender, subcutaneous nodules, erosions, joint deformities, rheumatoid factor, as well as dose, duration and type of DMARD and steroid therapy administered. We found a significant relationship among polyneuropathy and duration of RA, DAS28, HAQ, as well as abnormal NSS and NDS values. The durations of RA and DAS28 were also associated with a four- and three fold increase in the risk of polyneuropathy, respectively. CONCLUSION: Mild symmetric sensory or sensorimotor axonal polyneuropathies are common in RA patients and it is difficult to distinguish the symptoms of polyneuropathy from those of arthritis. An electrophysiological examination should be routinely carried out especially when patients have had a long disease duration and high scores for DAS28, HAQ, NSS and NDS. PMID- 20307378 TI - A double-blind, randomized, placebo-controlled, parallel-group study of Sativex, in subjects with symptoms of spasticity due to multiple sclerosis. AB - BACKGROUND: Muscle spasticity is common in multiple sclerosis (MS), occurring in more than 60% of patients. OBJECTIVE: To compare Sativex with placebo in relieving symptoms of spasticity due to MS. METHODS: A 15-week, multicenter, double-blind, randomized, placebo-controlled, parallel-group study in 337 subjects with MS spasticity not fully relieved with current anti-spasticity therapy. RESULTS: The primary endpoint was a spasticity 0-10 numeric rating scale (NRS). Intention-to-treat (ITT) analysis showed a non-significant improvement in NRS score, in favor of Sativex. The per protocol (PP) population (79% of subjects) change in NRS score and responder analyses (> or =30% improvement from baseline) were both significantly superior for Sativex, compared with placebo: 1.3 versus -0.8 points (change from baseline, p=0.035); and 36% versus 24% (responders, p=0.040). These were supported by the time to response (ITT: p=0.068; PP: p=0.025) analyses, carer global impression of change assessment (p=0.013) and timed 10-meter walk (p=0.042). Among the subjects who achieved a > or =30% response in spasticity with Sativex, 98, 94 and 73% reported improvements of 10, 20 and 30%, respectively, at least once during the first 4 weeks of treatment. Sativex was generally well tolerated, with most adverse events reported being mild-to-moderate in severity. DISCUSSION AND CONCLUSIONS: The 0-10 NRS and responder PP analyses demonstrated that Sativex treatment resulted in a significant reduction in treatment-resistant spasticity, in subjects with advanced MS and severe spasticity. The response observed within the first 4 weeks of treatment appears to be a useful aid to prediction of responder/non-responder status. PMID- 20307379 TI - Theory of mind skills 1 year after traumatic brain injury in 6- to 8-year-old children. AB - This study examined the longer-term effects of traumatic brain injury (TBI) on theory of mind (ToM) skills of children who were between the ages of 5 and 7 years at the time of injury. Fifty-two children with orthopaedic injury, 30 children with moderate TBI, and 12 children with severe TBI were evaluated approximately 1 year post-injury (mean age=6.98 years, SD=0.59, range=6.02-8.26). Children with severe TBI did not engage in representation of first- and second order mental states at a developmental level comparable to their peers, suggesting stagnation or lack of development, as well as regression of putatively existing ToM skills. Age, task-specific cognitive demands, and verbal abilities were strong predictors of ToM performance. However, even after taking those factors into account, children with severe TBI had poorer ToM performance than children with orthopaedic injuries. PMID- 20307380 TI - Multicentre randomised controlled trial of the clinical and cost-effectiveness of a bypass-surgery-first versus a balloon-angioplasty-first revascularisation strategy for severe limb ischaemia due to infrainguinal disease. The Bypass versus Angioplasty in Severe Ischaemia of the Leg (BASIL) trial. AB - OBJECTIVE: To compare a 'bypass-surgery-first' with a 'balloon-angioplasty-first' revascularisation strategy in patients with severe limb ischaemia (SLI) due to infrainguinal disease requiring immediate/early revascularisation. DESIGN: A stratified randomised controlled trial. A Delphi consensus study of vascular surgeons' and interventional radiologists' views on SLI treatment was performed before the trial. SETTING: Twenty-seven UK hospitals. PARTICIPANTS: Patients presenting with SLI as the result of infrainguinal atherosclerosis and who, in the opinion of the responsible consultant vascular surgeon and interventional radiologist, required and were suitable for both surgery and angioplasty. INTERVENTIONS: Patients were randomised to either 'bypass-surgery-first' or 'balloon-angioplasty-first' revascularisation strategies. MAIN OUTCOME MEASURES: The primary end point was amputation-free survival (AFS); secondary end points were overall survival (OS), health-related quality of life (HRQoL) and cost effective use of hospital resources. RESULTS: AFS at 1 and 3 years was not significantly different for surgery and angioplasty. Interim analysis showed that surgery was associated with significantly lower immediate failure, higher 30-day morbidity and lower 12-month reintervention rates than angioplasty; 30-day mortality was similar. Beyond 2 years from randomisation, hazard ratios (HRs) were significantly reduced for both AFS (adjusted HR 0.37; 95% CI 0.17 to 0.77; p = 0.008) and OS (HR 0.34; 95% CI 0.17 to 0.71; p = 0.004) for surgery relative to angioplasty. By 2008 all but four patients had been followed for 3 years, some for over 7 years: 250 (56%) were dead, 168 (38%) were alive without amputation and 30 (7%) were alive with amputation. Considering the follow-up period as a whole, AFS and OS did not differ between treatments but for patients surviving beyond 2 years from randomisation, bypass was associated with reduced HRs for AFS (HR 0.85; 95% CI 0.50 to 1.07; p = 0.108) and OS (HR 0.61; 95% CI 0.50 to 0.75; p = 0.009), equating to an increase in restricted mean OS of 7.3 months (p = 0.02) and AFS of 5.9 months (p = 0.06) during the subsequent follow-up period. Vein bypasses and angioplasties performed better than prosthetic bypasses. HRQoL was non-significantly better in the surgery group; amputation was associated with a significant reduction in HRQoL. Over the first year, hospital costs for bypass were significantly higher (difference 5420 pounds; 95% CI 1547 pounds to 9294 pounds) than for angioplasty. However, by 3 and at 7 years the differences in cost between the two strategies were no longer significant. Patients randomised to surgery lived, on average, 29 days longer at an additional average cost of 2310 pounds. A 36-month perspective showed not significantly different mean quality-adjusted life times for angioplasty and surgery. The Delphi study revealed substantial disagreement between and among surgeons and radiologists on the appropriateness of bypass surgery or balloon angioplasty. CONCLUSIONS: The findings of our study suggest that in patients with SLI due to infrainguinal disease the decision whether to perform bypass surgery or balloon angioplasty first appears to depend upon anticipated life expectancy. Patients expected to live less than 2 years should usually be offered balloon angioplasty first as it is associated with less morbidity and cost, and such patients are unlikely to enjoy the longer-term benefits of surgery. By contrast, those patients expected to live beyond 2 years should usually be offered bypass surgery first, especially where a vein is available as a conduit. Many patients who could not undergo a vein bypass would probably have been better served by a first attempt at balloon angioplasty than prosthetic bypass. The failure rate of angioplasty in SLI is high (c. 25%) and patients who underwent bypass after failed angioplasty fared significantly worse than those who underwent surgery as their first procedure. The interests of a significant proportion of BASIL patients may have been best served by primary amputation followed by high-quality rehabilitation. Further research is required to confirm or refute the BASIL findings and recommendations; validate the BASIL survival prediction model in a separate cohort of patients with SLI; examine the clinical and cost-effectiveness of new endovascular techniques and devices; and compare revascularisation with primary amputation and with best medical and nursing care in those SLI patients with the poorest survival prospects. TRIAL REGISTRATION: Current Controlled Trials ISRCTN45398889. PMID- 20307381 TI - Regulatory controversies surround blood glucose monitoring devices. PMID- 20307382 TI - Postprandial insulin and triglycerides after different breakfast meal challenges: use of finger stick capillary dried blood spots to study postprandial dysmetabolism. AB - BACKGROUND: High levels of insulin and lipids following a meal are recognized risk factors for atherosclerosis. Monitoring such risk factors in the general population is hampered by the inconvenience of venipuncture blood collection, particularly for both premeal and postmeal analyses. This study examined insulin and triglyceride levels in dried blood spots (DBSs) collected after different breakfast meal challenges to assess the potential of this method for risk assessment. METHODS: Glucose levels were measured using a glucose meter, and insulin and triglycerides were determined in DBS samples collected from 19 healthy volunteers before and at four time points up to 2.5 h after consuming each of five typical breakfast meals varying in nutritional composition. RESULTS: At 2 h, glucose was within normal postprandial values (<140 mg/dl) for all meals; significantly lower glucose was seen after meal 2 (the lowest carbohydrate content) compared to the other meals. Insulin returned to normal fasting levels (<15 microIU/ml) in significantly more subjects (90%) after meal 2 and significantly fewer subjects (31%) after meal 4 (highest carbohydrate content) than the other meals. Triglycerides were elevated to a similar extent in all subjects, with no significant differences between meals; levels were still rising at 2.5 h. CONCLUSIONS: Subjects were able to collect blood spots with minimum disruption to their normal daily activities. Relative ease of collection, analyte stability in dried blood, and the close correlation with serum levels that we have previously demonstrated makes DBS a convenient and simple tool for assessing the individual impact of different diets on postprandial dysmetabolism. PMID- 20307383 TI - Analysis of hemoglobin A1c from dried blood spot samples with the Tina-quantR II immunoturbidimetric method. AB - BACKGROUND: Hemoglobin A1c (HbA1c) has been endorsed as a tool for the diagnosis of diabetes. This test requires instrumentation that may not be available in underdeveloped areas. Dried blood spot (DBS) samples collected by finger stick procedures offer a mechanism to transport samples to laboratories that do measure HbA1c. METHODS: Whole blood (ethylenediaminetetraacetic acid) was applied to Ahlstrom 226 filter paper. These DBS samples were compared to whole blood samples using the Roche Tina-quant II immunoturbidometric assay. Hemoglobin A1c stability on DBS was assessed at three temperatures-4, 25, and 40 degrees C-for up to 9 days. A 44-day study was also done for DBS at 20-25 degrees C. RESULTS: The Tina quant II DBS method showed excellent agreement with whole blood HbA1c results (r(2) = 0.99) with a slight positive mean bias of 0.08 +/- 0.04% HbA1c (95% confidence interval). The variation in HbA1c on DBS samples subjected to different temperatures and times did not exceed 5.6%. CONCLUSIONS: Dried blood spot samples represent an alternative to whole blood for HbA1c by measurement when transporting whole blood is not feasible. PMID- 20307384 TI - Maximizing deoxyribonucleic acid yield from dried blood spots. AB - BACKGROUND: One source of deoxyribonucleic acid (DNA) for genetic studies is the utilization of dried blood spots stored on paper cards (Guthrie cards) collected shortly after birth. These cards represent an important source of material for epidemiologic and population-based genetic studies. Extraction of DNA from these cards can lead to variable amounts of recovered DNA. We report here results of our efforts to maximize yield from this valuable, but nonrenewable, resource. METHOD: Commercial methods of DNA extraction from blood cards were used, and protocol modifications were introduced that enhanced DNA yield. RESULTS: Use of a commercial solvent prior to DNA extraction steps gave greater yields than extraction without the solvent. Modification of the elution step by use of prewarmed extraction buffer and a soaking step at an elevated temperature increased yield by 6- to 10-fold. CONCLUSIONS: The modified DNA extraction method yielded as much as 660 ng of DNA from a single 5-mm-diameter punch of a blood spot card. The DNA performed well in downstream, polymerase chain reaction-based applications. PMID- 20307385 TI - Use of dried blood spots: an ideal tool for medical anthropology "in the field". AB - The use of dried whole blood spot samples provides medical anthropological researchers-especially those working in remote, isolated communities-with several advantages over traditional methods. Anthropological research utilizing venous drawn blood samples can create challenges in terms of phlebotomy training, personnel needs, storage and transportation requirements, and participant discomfort. Alternatively, research utilizing dried blood spot samples, via finger stick collection techniques, eliminates or reduces these problems greatly. While the use of dried blood spots is often the best sampling option for anthropologists or other population-level researchers, the method does have some limitations. Nevertheless, as the number of dried blood spot analyte protocols continues to increase, the logistical and participant advantages of dried blood spot methods assure their increased utility in biomedical anthropological research in the future. PMID- 20307386 TI - Utility of dried blood spots for measurement of cholesterol and triglycerides in a surveillance study. AB - BACKGROUND: Developing countries are facing a rise in noncommunicable diseases (NCD), which is a cause for concern. The World Health Organization has recommended a stepwise approach for NCD risk factor surveillance. Screening for risk factors in remote populations is difficult due to lack of resources and technical expertise, including standardized laboratory facilities. The collection of samples on filter paper for the assessment of risk factors circumvents the need for blood processing, storage, and shipment at ultralow temperatures. METHOD: Samples were collected on 3-mm Whatman filter paper from one industry (National Thermal Power Corporation) located in the periphery of Delhi as part of a surveillance carried out in industries from different parts of India. Total cholesterol was measured in serum and dried blood by the cholesterol oxidase/p aminophenazone method and triglycerides by the glycerophosphate oxidase peroxidase/aminophenazone method. Values obtained by the two methods were compared using Pearson correlation, and Bland-Altman plots were prepared to assess bias. RESULTS: The correlation coefficient "r" was 0.78 for cholesterol and 0.94 for triglycerides between dried blood spots and serum. Bland-Altman plots suggest that differences in values obtained by the two methods were within two standard deviations for most of the samples. CONCLUSIONS: Blood samples dried on filter paper can be a successful option for population screening in remote areas, provided preanalytical variations arising due to the method of blood spot preparation and storage are well controlled. PMID- 20307387 TI - A hazard analysis for a generic insulin infusion pump. AB - BACKGROUND: Researchers at the Food and Drug Administration (FDA)/Center for Device and Radiological Health/Office of Science and Engineering Laboratories have been exploring the concept of model-based engineering as a means for improving the quality of medical device software. Insulin pumps were chosen as a research subject because their design provides the desired degree of research complexity and these types of devices present an ongoing regulatory challenge. METHODS: Insulin pump hazards and their contributing factors are considered in the context of a highly abstract generic insulin infusion pump (GIIP) model. Hazards were identified by consulting with manufacturers, pump users, and clinicians; by reviewing national and international standards and adverse event reports collected by the FDA; and from workshops sponsored by Diabetes Technology Society. This information has been consolidated in tabular form to facilitate further community analysis and discussion. RESULTS: A generic insulin infusion pump model architecture has been established. A fairly comprehensive hazard analysis document, corresponding to the GIIP model, is presented in this article. CONCLUSIONS: We believe that this work represents the genesis of an insulin pump safety reference standard upon which future insulin pump designs can be based to help ensure a basic level of safety. More interaction with the diabetes community is needed to assure the quality of this safety modeling process. PMID- 20307389 TI - A disposable tear glucose biosensor-part 1: design and concept testing. AB - BACKGROUND: Tear glucose has been suggested previously as a potential approach for the noninvasive estimation of blood glucose. While the topic remains unresolved, an overview of previous studies suggests the importance of a tear sampling approach and warrants new technology development. A concept device is presented that meets the needs of a tear glucose biosensor. METHODS: Three approaches to chronoamperometric glucose sensing were evaluated, including glucose oxidase mediated by potassium ferricyanide or oxygen with a hydrogen peroxide catalyst, Prussian blue, and potassium ferricyanide-mediated glucose dehydrogenase. For tear sampling, calcium alginate, poly(2-hydroxyethyl methacrylate), and polyurethane foam were screened as an absorbent tear sampling material. A quantitative model based on the proposed function of concept device was created. RESULTS: For glucose sensing, it was found that potassium ferricyanide with glucose dehydrogenase was ideal, featuring oxygen insensitivity, long-term stability, and a lower limit of detection of 2 muM glucose. Polyurethane foam possessed all of the required characteristics for tear sampling, including reproducible sampling from a hydrogel-simulated, eye surface (4.2 +/- 0.5 microl; n = 8). It is estimated that 100 microM of glucose tear fluid would yield 135 nA (14.9% relative standard deviation). CONCLUSION: A novel concept device for tear glucose sampling was presented, and the key functions of this device were tested and used to model the performance of the final device. Based on these promising initial results, the device is achievable and within reach of current technical capabilities, setting the stage for prototype development. PMID- 20307390 TI - A disposable tear glucose biosensor-part 2: system integration and model validation. AB - BACKGROUND: We presented a concept for a tear glucose sensor system in an article by Bishop and colleagues in this issue of Journal of Diabetes Science and Technology. A unique solution to collect tear fluid and measure glucose was developed. Individual components were selected, tested, and optimized, and system error modeling was performed. Further data on prototype testing are now provided. METHODS: An integrated fluidics portion of the prototype was designed, cast, and tested. A sensor was created using screen-printed sensors integrated with a silicone rubber fluidics system and absorbent polyurethane foam. A simulated eye surface was prepared using fluid-saturated poly(2-hydroxyethyl methacrylate) sheets, and the disposable prototype was tested for both reproducibility at 0, 200, and 400 microM glucose (n = 7) and dynamic range of glucose detection from 0 to 1000 microM glucose. RESULTS: From the replicated runs, an established relative standard deviation of 15.8% was calculated at 200 microM and a lower limit of detection was calculated at 43.4 microM. A linear dynamic range was demonstrated from 0 to 1000 microM with an R(2) of 99.56%. The previously developed model predicted a 14.9% variation. This compares to the observed variance of 15.8% measured at 200 microM glucose. CONCLUSION: With the newly designed fluidics component, an integrated tear glucose prototype was assembled and tested. Testing of this integrated prototype demonstrated a satisfactory lower limit of detection for measuring glucose concentration in tears and was reproducible across a physiological sampling range. The next step in the device design process will be initial animal studies to evaluate the current prototype for factors such as eye irritation, ease of use, and correlation with blood glucose. PMID- 20307388 TI - What makes tight glycemic control tight? The impact of variability and nutrition in two clinical studies. AB - INTRODUCTION: Tight glycemic control (TGC) remains controversial while successful, consistent, and effective protocols remain elusive. This research analyzes data from two TGC trials for root causes of the differences achieved in control and thus potentially in glycemic and other outcomes. The goal is to uncover aspects of successful TGC and delineate the impact of differences in cohorts. METHODS: A retrospective analysis was conducted using records from a 211 patient subset of the GluControl trial taken in Liege, Belgium, and 393 patients from Specialized Relative Insulin Nutrition Titration (SPRINT) in New Zealand. Specialized Relative Insulin Nutrition Titration targeted 4.0-6.0 mmol/liter, similar to the GluControl A (N = 142) target of 4.4-6.1 mmol/liter. The GluControl B (N = 69) target was 7.8-10.0 mmol/liter. Cohorts were matched by Acute Physiology and Chronic Health Evaluation II score and percentage males (p > .35); however, the GluControl cohort was slightly older (p = .011). Overall cohort and per-patient comparisons (median, interquartile range) are shown for (a) glycemic levels achieved, (b) nutrition from carbohydrate (all sources), and (c) insulin dosing for this analysis. Intra- and interpatient variability were examined using clinically validated model-based insulin sensitivity metric and its hour-to-hour variation. RESULTS: Cohort blood glucose were as follows: SPRINT, 5.7 (5.0-6.6) mmol/liter; GluControl A, 6.3 (5.3-7.6) mmol/liter; and GluControl B, 8.2 (6.9-9.4) mmol/liter. Insulin dosing was 3.0 (1.0-3.0), 1.5 (0.5-3), and 0.7 (0.0-1.7) U/h, respectively. Nutrition from carbohydrate (all sources) was 435.5 (259.2-539.1), 311.0 (0.0-933.1), and 622.1 (103.7-1036.8) kcal/day, respectively. Median per-patient results for blood glucose were 5.8 (5.3-6.4), 6.4 (5.9-6.9), and 8.3 (7.6-8.8) mmol/liter. Insulin doses were 3.0 (2.0-3.0), 1.5 (0.8-2.0), and 0.5 (0.0-1.0) U/h. Carbohydrate administration was 383.6 (207.4-497.7), 103.7 (0.0-829.4), and 207.4 (0.0-725.8) kcal/day. Overall, SPRINT gave approximately 2x more insulin with a 3-4x narrower, but generally non zero, range of nutritional input to achieve equally TGC with less hypoglycemia. Specialized Relative Insulin Nutrition Titration had much less hypoglycemia (<2.2 mmol/liter), with 2% of patients, compared to GluControl A (7.7%) and GluControl B (2.9%), indicating much lower variability, with similar results for glucose levels <3.0 mmol/liter. Specialized Relative Insulin Nutrition Titration also had less hyperglycemia (>8.0 mmol/liter) than groups A and B. GluControl patients (A+B) had a approximately 2x wider range of insulin sensitivity than SPRINT. Hour to-hour variation was similar. Hence GluControl had greater interpatient variability but similar intrapatient variability. CONCLUSION: Protocols that dose insulin blind to carbohydrate administration can suffer greater outcome glycemic variability, even if average cohort glycemic targets are met. While the cohorts varied significantly in model-assessed insulin resistance, their variability was similar. Such significant intra- and interpatient variability is a further significant cause and marker of glycemic variability in TGC. The results strongly recommended that TGC protocols be explicitly designed to account for significant intra- and interpatient variability in insulin resistance, as well as specifying or having knowledge of carbohydrate administration to minimize variability in glycemic outcomes across diverse cohorts and/or centers. PMID- 20307391 TI - Electrochemical glucose biosensor of platinum nanospheres connected by carbon nanotubes. AB - BACKGROUND: Glucose biosensors comprised of nanomaterials such as carbon nanotubes (CNTs) and metallic nanoparticles offer enhanced electrochemical performance that produces highly sensitive glucose sensing. This article presents a facile biosensor fabrication and biofunctionalization procedure that utilizes CNTs electrochemically decorated with platinum (Pt) nanospheres to sense glucose amperometrically with high sensitivity. METHOD: Carbon nanotubes are grown in situ by microwave plasma chemical vapor deposition (MPCVD) and electro-chemically decorated with Pt nanospheres to form a CNT/Pt nanosphere composite biosensor. Carbon nanotube electrodes are immobilized with fluorescently labeled bovine serum albumin (BSA) and analyzed with fluorescence microscopy to demonstrate their biocompatibility. The enzyme glucose oxidase (GO(X)) is immobilized onto the CNT/Pt nanosphere biosensor by a simple drop-coat method for amperometric glucose sensing. RESULTS: Fluorescence microscopy demonstrates the biofunctionalization capability of the sensor by portraying adsorption of fluorescently labeled BSA unto MPCVD-grown CNT electrodes. The subsequent GO(X) CNT/Pt nanosphere biosensor demonstrates a high sensitivity toward H(2)O(2) (7.4 microA/mM/cm(2)) and glucose (70 microA/mM/cm(2)), with a glucose detection limit and response time of 380 nM (signal-to-noise ratio = 3) and 8 s (t(90%)), respectively. The apparent Michaelis-Menten constant (0.64 mM) of the biosensor also reflects the improved sensitivity of the immobilized GO(X)/nanomaterial complexes. CONCLUSIONS: The GO(X)-CNT/Pt nanosphere biosensor outperforms similar CNT, metallic nanoparticle, and more conventional carbon-based biosensors in terms of glucose sensitivity and detection limit. The biosensor fabrication and biofunctionalization scheme can easily be scaled and adapted for microsensors for physiological research applications that require highly sensitive glucose sensing. PMID- 20307392 TI - Fabrication of nanoindented electrodes for glucose detection. AB - BACKGROUND: The objective of this article was to design, fabricate, and evaluate a novel type of glucose biosensors based on the use of atomic force microscopy to create nanoindented electrodes (NIDEs) for the selective detection of glucose. METHODS: Atomic force microscopy nanoindentation techniques were extended to covalently immobilized glucose oxidase on NIDEs via composite hydrogel membranes composed of interpenetrating networks of inherently conductive poly(3,4 ethylenedioxythiophene) tetramethacrylate grown within ultraviolet cross-linked hydroxyethylmethacrylate-based hydrogels to produce an in vitro amperometric NIDE biosensor for the long-term monitoring of glucose. RESULTS: The calibration curve for glucose was linear from 0.25 to 20 mM. Results showed that the NIDE glucose biosensor has a much higher detection sensitivity of 0.32 microA/mM and rapid response times (<5 seconds). There was no interference from the competing interferent (fructose) present; the only interference was from species that react with H(2)O(2) (ascorbic acid). The linear equation was B(response) (microA) = 0.323 [glucose] (mM) + 0.634 (microA); n = 24, r(2) = 0.994. CONCLUSION: Results showed that the resultant NIDE glucose biosensor increases the dynamic range, device sensitivity, and response time and has excellent detecting performance for glucose. PMID- 20307393 TI - Mobile phone-based self-management tools for type 2 diabetes: the few touch application. AB - BACKGROUND: Mobile phones and other mobile information and communication technology applications and technologies hold great potential as a basis for powerful patient-operated self-management tools within diabetes. The work presented shows how such tools can be designed for supporting lifestyle changes among people with type 2 diabetes and how these were perceived by a group of 12 patients during a 6-month period. METHOD: The study used focus groups, interviews, feasibility testing, questionnaires, paper prototyping, and prototyping of both software and hardware components. The design process was iterative, addressing the various elements several times at an increasing level of detail. The final test of the application was done qualitatively in everyday settings in a cohort of 12 people with type 2 diabetes, aged 44-70 (four men and eight women). RESULTS: A mobile phone-based system called the Few Touch application was developed. The system includes an off-the-shelf blood glucose (BG) meter, a tailor-made step counter, and software for recording food habits and providing feedback on how users perform in relation to their own personal goals. User feedback from the 6-month user intervention demonstrated good usability of the tested system, and several of the participants adjusted their medication, food habits, and/or physical activity. Of the five different functionalities, the cohort considered the BG sensor system the best. CONCLUSIONS: It was shown that it is possible and feasible to design an application where several sensors and feedback applications are integrated in an overall system. The presented Few Touch application challenges people with type 2 diabetes to think about how they can improve their health, providing them with a way to capture and analyze relevant personal information about their disease. The half-year user intervention demonstrated that the system had a motivational effect on the users. PMID- 20307394 TI - Association of Indian Diabetes Risk Score with arterial stiffness in Asian Indian nondiabetic subjects: the Chennai Urban Rural Epidemiology Study (CURES-84). AB - OBJECTIVE: In this study, we aim to determine the association of Indian Diabetes Risk Score (IDRS) with augmentation index (AI), a preclinical marker of early atherosclerotic changes. METHODS: Subjects without known diabetes (n = 1985) were randomly selected from the Chennai Urban Rural Epidemiology Study, an ongoing population-based study on a representative population (aged >or=20 years) of Chennai, the largest city in Southern India. Augmentation index was measured using the Sphygmocor apparatus (Sphygmocor BPAS-1; PWV Medical, Sydney, Australia). Serum lipids were measured in an overnight fasting sample along with other biochemical parameters. Indian Diabetes Risk Score includes four parameters: age, abdominal obesity, family history of type 2 diabetes, and physical activity. RESULTS: Arterial stiffness values increased with an increase in IDRS. Subjects with IDRS >or=60 had significantly higher AI (24.6 +/- 7.2; p < .001) compared to subjects with an IDRS of 30-60 (16.4 +/- 5.5; p < .001) and with IDRS <30 (13.3 +/- 4.5), and the p for trend was statistically significant (<.001). Pearson correlation analysis in the total population revealed that AI was significantly correlated with age (p < .001), systolic and diastolic blood pressure (p < .001), IDRS (p < .001), glycated hemoglobin A1c (A1C) (p < .001), serum cholesterol (p < .001), serum triglycerides (p < .001), high-density lipoprotein (HDL) cholesterol (p < .001), low-density lipoprotein cholesterol (p < .001), and non-HDL cholesterol (p < .001). In linear regression analysis, IDRS showed a significant association with AI even after adjusting for blood pressure, smoking, insulin resistance, A1C, cholesterol, and triglycerides (beta = 6.388; p < .001). CONCLUSION: This study shows that, in addition to identifying unknown diabetes, IDRS also helps to identify those with arterial stiffness. PMID- 20307395 TI - Do differences in sleep architecture exist between persons with type 2 diabetes and nondiabetic controls? AB - BACKGROUND: It has been shown previously that the suppression of slow-wave sleep (SWS) markedly reduced insulin sensitivity and led to an impairment of glucose tolerance. We hypothesized that a decreased amount of SWS is a feature peculiar to subjects with type 2 diabetes. METHOD: A retrospective case-control study analyzed polysomnographic recordings and covariate data of 22 type 2 diabetic and 22 nondiabetic subjects [n = 44; 8 women, 36 men, aged 57.5 +/- 5.5 years, body mass index (BMI) 33.8 +/- 5.9 kg/m(2), apnea-hypopnea index (AHI) 29.6 +/- 22.2 episodes/hr] matched individually for sex, race, age, BMI, and severity of sleep related breathing disorders (SRBD). We assessed differences in sleep architecture between the study group and the control group. Primary end points included the percentage of total sleep time spent in each sleep stage. RESULTS: Despite similar age and severity of SRBD, subjects with type 2 diabetes demonstrated a significantly decreased amount of SWS (3.9 +/- 5.95% vs 8.4 +/- 4.57%; p = 0.012), increased percentage time in rapid eye movement sleep (24.1 +/- 12.14% vs 13.8 +/- 6.96%; p = 0.005), and higher arousal index (44.3 +/- 19.53/hr vs 35.7 +/- 12.67/hr; p = 0.037) compared to nondiabetic controls. After adjustment for sex, BMI, AHI, and smoking, age and presence of type 2 diabetes were independent predictors of the decreased SWS percentage (p = 0.001). Variables in this model accounted for 34% of the variance in the SWS percentage in our cohort. CONCLUSIONS: Results demonstrated distinct differences in sleep architecture in our cohort with decreased amounts of SWS in type 2 diabetes. These findings suggest that polysomnographic recognition of altered sleep architecture may be partially implicated in the early detection of persons with type 2 diabetes. PMID- 20307396 TI - Half-unit dose accuracy with HumaPen Luxura HD: an insulin pen for patients who need precise dosing. AB - BACKGROUND: The HumaPen Luxura HD insulin pen (Eli Lilly and Company, Indianapolis, IN) was originally designed to deliver accurate doses in half-unit increments from 1 to 30 units. Laboratory testing examined the accuracy of the initial 0.5-unit dose within a 95/95% tolerance interval with respect to a specification of +/-0.5 unit (+/-0.005 ml). METHODS: After priming, operators recorded the first 0.5 unit. Data were analyzed using k-value targets. RESULTS: While examining 577 half-unit doses per device lot, test temperature, operator, or test liquid, at least 95% of the doses were accurate with 95% confidence. All data points were within +/-0.5 unit (+/-0.005 ml). CONCLUSIONS: Dose accuracy of the initial half-unit is achieved with the HumaPen Luxura HD insulin pen. PMID- 20307397 TI - An analysis of the HumaPen Luxura HD pen: what is the role of 0.5-unit insulin dosing? AB - The HumaPen Luxura HD is an insulin pen device that has the ability to deliver insulin in half-unit increments. This study demonstrates the precision of this pen device using a computer-controlled dose accuracy glide force system. Although one other half-unit pen device is currently on the market, we are not aware of any studies using a similar methodology to verify its precision and accuracy. Clinical experience in treating a select group of adults with diabetes demonstrates the need for such a device. Although there are no outcome studies, this device should help to improve glycemic control and reduce hypoglycemia in such patients. We believe a half-unit insulin pen device is beneficial to more than just the pediatric population, and therefore, this device represents an improvement in present technology. PMID- 20307398 TI - Effects of controlled-release alpha lipoic acid in lean, nondiabetic patients with polycystic ovary syndrome. AB - BACKGROUND: The purpose of this study was to determine whether a preparation of controlled-release alpha lipoic acid (CRLA) influences features of the polycystic ovary syndrome (PCOS). METHODS: We administered CRLA 600 mg twice daily for 16 weeks to six lean, nondiabetic patients with PCOS. Insulin sensitivity was measured by the euglycemic, hyperinsulinemic clamp. Plasma lipids were measured by vertical ultracentrifugation. Oxidative stress markers were measured in serum. RESULTS: At the end of 16 weeks of CRLA treatment, there was a 13.5% improvement in insulin sensitivity as determined by the euglycemic, hyperinsulinemic clamp (p < .03). There was also a lowering of triglyceride levels (p < .04) and a shift in the distribution of low-density lipoprotein (LDL) particles toward the larger, more buoyant LDL subclass fraction. Two of the subjects who were not on oral contraception had an increased number of menstrual cycles. Controlled-release alpha lipoic acid treatment, however, was neither associated with an increase in plasma antioxidant capacity nor with a reduction in plasma lipid oxidation products. CONCLUSIONS: These data suggest that the CRLA has positive effects on the PCOS phenotype. The effects of CRLA, however, may have been exerted through a mechanism not involving changes in oxidative stress. PMID- 20307400 TI - Characterization of cardiovascular outcomes in a type 2 diabetes glucose supply and insulin demand model. AB - BACKGROUND: The nonsignificant reduction in macrovascular outcomes observed in Action to Control Cardiovascular Risk in Diabetes; Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation; and the Veterans Affairs Diabetes Trial have collectively created uncertainty with respect toward the proper extent of blood glucose reduction and also the optimal therapeutic choice to attain the reduction. In the article entitled "Glucose Supply and Insulin Demand Dynamics of Antidiabetic Agents" in this issue of Journal of Diabetes Science and Technology, we presented data for a pharmacokinetic/pharmacodynamic model that characterizes the effect of conventional antidiabetic therapies on the glucose supply and insulin demand dynamic. Here, it is our objective to test the hypothesis that, in conjunction with hemoglobin A1c (HbA1c), patients managed on the glucose supply side of the model would have fewer cardiovascular events versus those managed on the insulin demand side. METHODS: To test this hypothesis, the electronic medical records of a group model health maintenance organization were queried to compile a population of patients meeting the following inclusion criteria: (1) type 2 diabetes mellitus (T2DM), (2) known date of T2DM diagnosis; (3) ICD-9 or CPT code identification and chart review confirmation of a first major cardiovascular event (myocardial infarction, coronary artery bypass graft, or angioplasty),(4) five years of continuous eligibility, and (5) on antidiabetic therapy at the beginning of the 5-year observation period. These patients were subsequently matched (1:1) to T2DM patients meeting the same criteria who had not experienced an event and were analyzed for differences in glucose control (HbA1C), the glucose supply:insulin demand dynamic (SD ratio), and categorical combinations of both parameters. RESULTS: Fifty cardiovascular event patients met inclusion criteria and were matched to controls. No difference was observed for the average HbA1c or SD ratio between patients experiencing an event and controls (7.5 +/- 1.0% versus 7.3 +/- 0.9%, p = .275, and 1.2 +/- 0.3 versus 1.3 +/- 0.3, p = .205, respectively). Likewise, for categorical representations, there were no differences in event rate at the pre-identified breakpoints (HbA1c >or=7% versus <7%; 72% versus 64%, p = .391, and SD ratio >or=1 versus <1; 68% versus 76%, p = .373, >or=1.25 versus <1.25; 42% versus 56%, p = .161, >or=1.5 versus <1.5; 22% versus 30%, p = .362, respectively). Analyzing the combined effect of glucose control and the SD dynamic, patients managed at higher glucose values and on the insulin demand side of the model (HbA1c >or=7% and SD ratio <1.25) tended to have greater cardiovascular risk than those managed at an HbA1c <7%, or HbA1c >or=7% with an SD ratio >or=1.25 (61% versus 39%; p = .096). CONCLUSION: Independently, more aggressive HbA1c reduction and higher SD ratio values were not independently associated with a reduction in cardiovascular outcomes. Combining the parameters, it would appear that patients managed at higher glucose values and on the insulin demand side of the model may have increased cardiovascular risk. Based on these findings, it is pertinent to conduct subsequent works to refine SD ratio estimates and apply the model to larger, long-term T2DM cardiovascular outcome trials. J Diabetes Sci Technol 2010;4(2):382-390. PMID- 20307399 TI - Glucose supply and insulin demand dynamics of antidiabetic agents. AB - BACKGROUND: For microvascular outcomes, there is compelling historical and contemporary evidence for intensive blood glucose reduction in patients with either type 1 diabetes mellitus (T1DM) or type 2 diabetes mellitus (T2DM). There is also strong evidence to support macrovascular benefit with intensive blood glucose reduction in T1DM. Similar evidence remains elusive for T2DM. Because cardiovascular outcome trials utilizing conventional algorithms to attain intensive blood glucose reduction have not demonstrated superiority to less aggressive blood glucose reduction (Action to Control Cardiovascular Risk in Diabetes; Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation; and Veterans Affairs Diabetes Trial), it should be considered that the means by which the blood glucose is reduced may be as important as the actual blood glucose. METHODS: By identifying quantitative differences between antidiabetic agents on carbohydrate exposure (CE), hepatic glucose uptake (HGU), hepatic gluconeogenesis (GNG), insulin resistance (IR), peripheral glucose uptake (PGU), and peripheral insulin exposure (PIE), we created a pharmacokinetic/pharmacodynamic model to characterize the effect of the agents on the glucose supply and insulin demand dynamic. Glucose supply was defined as the cumulative percentage decrease in CE, increase in HGU, decrease in GNG, and decrease in IR, while insulin demand was defined as the cumulative percentage increase in PIE and PGU. With the glucose supply and insulin demand effects of each antidiabetic agent summated, the glucose supply (numerator) was divided by the insulin demand (denominator) to create a value representative of the glucose supply and insulin demand dynamic (SD ratio). RESULTS: Alpha glucosidase inhibitors (1.25), metformin (2.20), and thiazolidinediones (TZDs; 1.25-1.32) demonstrate a greater effect on glucose supply (SD ratio >1), while secretagogues (0.69-0.81), basal insulins (0.77-0.79), and bolus insulins (0.62 0.67) demonstrate a greater effect on insulin demand (SD ratio <1). CONCLUSION: Alpha-glucosidase inhibitors, metformin, and TZDs demonstrate a greater effect on glucose supply, while secretagogues, basal insulin, and bolus insulin demonstrate a greater effect on insulin demand. Because T2DM cardiovascular outcome trials have not demonstrated macrovascular benefit with more aggressive blood glucose reduction when using conventional algorithms that predominantly focus on insulin demand, it would appear logical to consider a model that incorporates both the extent of blood glucose lowering (hemoglobin A1c) and the means by which the blood glucose was reduced (SD ratio) when considering macrovascular outcomes. PMID- 20307401 TI - Real-time glucose estimation algorithm for continuous glucose monitoring using autoregressive models. AB - BACKGROUND: Continuous glucose monitors (CGMs) present a problem of lack of accuracy, especially in the lower range, sometimes leading to missed or false hypoglycemia. A new algorithm is presented here aimed at improving the measurement accuracy and hypoglycemia detection. Its core is the estimation of blood glucose (BG) in real time (RT) from CGM intensity readings using autoregressive (AR) models. METHODS: Eighteen patients with type 1 diabetes were monitored for three days (one at the hospital and two at home) using the CGMS Gold. For these patients, BG samples were taken every 15 min for 2 h after meals and every half hour otherwise during the first day. The relationship between the current measured by the CGMS Gold and BG was learned by an AR model, allowing its RT estimation. New capillary glucose measurements were used to correct the model BG estimations. RESULTS: A total of 563 paired points were obtained from BG and monitor readings to validate the new algorithm. 98.5% of paired points fell in zones A+B of the Clarke error grid analysis with the proposed algorithm. The overall mean and median relative absolute differences (RADs) were 9.6% and 6.7%. Measurements meeting International Organization for Standardization (ISO) criteria were 88.7%. In the hypoglycemic range, the mean and median RADs were 8.1% and 6.0%, and measurements meeting ISO criteria were 86.7%. The sensitivity and specificity with respect to hypoglycemia detection were 91.5% and 95.0%. CONCLUSIONS: The performance measured with both clinical and numerical accuracy metrics illustrates the improved accuracy of the proposed algorithm compared with values presented in the literature. A significant improvement in hypoglycemia detection was also observed. PMID- 20307402 TI - Continuous glucose monitoring: real-time algorithms for calibration, filtering, and alarms. AB - Algorithms for real-time use in continuous glucose monitors are reviewed, including calibration, filtering of noisy signals, glucose predictions for hypoglycemic and hyperglycemic alarms, compensation for capillary blood glucose to sensor time lags, and fault detection for sensor degradation and dropouts. A tutorial on Kalman filtering for real-time estimation, prediction, and lag compensation is presented and demonstrated via simulation examples. A limited number of fault detection methods for signal degradation and dropout have been published, making that an important area for future work. PMID- 20307403 TI - Review of the mechanism of action and clinical efficacy of recombinant human hyaluronidase coadministration with current prandial insulin formulations. AB - For patients with type 1 or type 2 diabetes, achieving good glycemic control is critical for successful treatment outcomes. As many patients remain unable to reach glycemic goals with currently available rapid-acting analog insulins, ultrafast insulin products are being developed that provide an even faster pharmacokinetic profile compared with current rapid prandial insulin products. The overall strategy of these ultrafast insulin products is to better mimic the normal physiologic response to insulin that occurs in healthy individuals to further improve glycemic control. Recombinant human hyaluronidase (rHuPH20) is a genetically engineered soluble hyaluronidase approved by the U.S. Food and Drug Administration as an adjuvant to increase the absorption and dispersion of other injected drugs; mammalian hyaluronidases as a class have over 6 decades of clinical use supporting the safety and/or efficacy of hyaluronidase coadministration. Clinical findings have demonstrated that coadministration of rHuPH20 with insulin or an insulin analog achieved faster systemic absorption, reduced inter- and intrapatient variability of insulin absorption, and achieved faster metabolic effects compared with injection of either insulin formulation alone. The magnitude of this acceleration is similar to the incrementally faster absorption of prandial insulin analogs as compared with regular insulin. In addition, coadministration of rHuPH20 with regular insulin or insulin analog also improved the achievement of prandial glycemic targets. Thus, rHuPH20 coadministration shows promise as a method of establishing a more rapid insulin profile to prandial insulin in patients with diabetes and has the potential to yield substantial improvements in postprandial glycemic excursion. PMID- 20307405 TI - Self-monitoring of blood glucose: practical aspects. AB - Self-monitoring of blood glucose (SMBG) should be part of a regular management plan for patients with diabetes. Self-monitoring of blood glucose provides information regarding an individual's dynamic blood glucose profile. This information can help with the appropriate scheduling of food, activity, and medication. It is also required for understanding of the timing of blood glucose variations. Lack of regular SMBG predicts hospitalization for diabetes-related complications. Self-monitoring of blood glucose is an essential tool for people with diabetes who are taking insulin or for those who experience fluctuations in their blood glucose levels, especially hypoglycemia. Application of practical aspects that aid in easy management of SMBG makes the task of checking blood glucose more achievable. For patients taking insulin and adjusting their dose, SMBG is needed for self-management. For others receiving oral medication, profiling glucose trends and the confirmation of high or low blood glucose can be a useful addendum to successful management. PMID- 20307404 TI - BALANCE (Bioengineering Approaches for Lifestyle Activity and Nutrition Continuous Engagement): developing new technology for monitoring energy balance in real time. AB - Methods that measure energy balance accurately in real time represent promising avenues to address the obesity epidemic. We developed an electronic food diary on a mobile phone that includes an energy balance visualization and computes and displays the difference between energy intake from food entries and energy expenditure from a multiple-sensor device that provides objective estimates of energy expenditure in real time. A geographic information system dataset containing locations associated with activity and eating episodes is integrated with an ArcPad mapping application on the phone to provide users with a visual display of food sources and locations associated with physical activity within their proximal environment. This innovative tool captures peoples' movement through space and time under free-living conditions and could potentially have many health-related applications in the future. PMID- 20307406 TI - Professional continuous glucose monitoring in clinical practice 2010. AB - Professional continuous glucose monitoring (PCGM) is a 3-5 day test done to evaluate diabetes control. The PCGM test uses interstitial glucose measurements done every 5 min with a glucose-oxidase-impregnated membrane. The PCGM test evaluates glucose control retrospectively with the glucose results being unknown to the patient until the results are downloaded after the testing period. The PCGM test allows the practitioner and patient to evaluate the effect of diet, physical activity, medications, and lifestyle events on glucose control during the 24 h period. Developing a PCGM program at a medical office involves understanding reimbursement issues and having trained staff and a process in place to initiate the test and download and interpret the data. PMID- 20307407 TI - Bluetooth low energy: wireless connectivity for medical monitoring. AB - Electronic wireless sensors could cut medical costs by enabling physicians to remotely monitor vital signs such as blood pressure, blood glucose, and blood oxygenation while patients remain at home. According to the IDC report "Worldwide Bluetooth Semiconductor 2008-2012 Forecast," published November 2008, a forthcoming radio frequency communication ("wireless connectivity") standard, Bluetooth low energy, will link wireless sensors via radio signals to the 70% of cell phones and computers likely to be fitted with the next generation of Bluetooth wireless technology, leveraging a ready-built infrastructure for data transmission. Analysis of trends indicated by this data can help physicians better manage diseases such as diabetes. The technology also addresses the concerns of cost, compatibility, and interoperability that have previously stalled widespread adoption of wireless technology in medical applications. PMID- 20307408 TI - Driving with diabetes in the future: in-vehicle medical monitoring. AB - The motor car is a ubiquitous feature of modern life, and most of us spend significant amounts of time in a car, behind the wheel. Driving a vehicle requires complex coordination of cognitive, motor, and sensory skills. All of these aspects can be affected adversely by diabetes per se, with hypoglycemia being the main concern for people with diabetes who drive. Here we introduce the concept of using the motor vehicle as a device to collect and deliver physiological and clinical information, which, in turn, may enable more people to drive more safely by reducing the chances of medical mishaps behind the wheel. This is particularly relevant for people living with diabetes who are at risk from a number of medical conditions that have the potential to have an impact on safe driving. The development of in-vehicle medical monitoring presents a new opportunity for novel collaborations between two industries, which have safety as a core value. PMID- 20307409 TI - The role of technology and the chronic care model. AB - Innovative technological approaches offer great promise for enhancing the quality of care and improved access. A chronic care model has been shown repeatedly to improve outcomes. The elements of the model include the health system, community, self-management support, decision support, clinical information systems, and delivery system redesign. Understanding opportunities to apply technology to the chronic care model is critically important as the rates of diabetes escalate and quality care becomes a priority for health systems. PMID- 20307411 TI - Second insulin pump safety meeting: summary report. AB - Diabetes Technology Society facilitated a second meeting of insulin pump experts at Mills-Peninsula Health Services, San Mateo, California on November 4, 2009, at the request of the Food and Drug Administration, Center for Devices and Radiological Health, Office of Science and Engineering Laboratories. The first such meeting was held in Bethesda, Maryland, on November 12, 2008. The group of physicians, nurses, diabetes educators, and engineers from across the United States discussed safety issues in insulin pump therapy and recommended adjustments to current insulin pump design and use to enhance overall safety. The meeting discussed safety issues in the context of pump operation; software; hardware; physical structure; electrical, biological, and chemical considerations; use; and environment from engineering, medical, nursing, and pump/user perspectives. There was consensus among meeting participants that insulin pump designs have made great progress in improving the quality of life of people with diabetes, but much more remains to be done. PMID- 20307413 TI - FDA meeting: Clinical accuracy requirements for point of care blood glucose meters. PMID- 20307414 TI - Insulin glargine and incidence of cancer--an ongoing debate. PMID- 20307415 TI - Does patient satisfaction with foot surgery change over time? AB - BACKGROUND: The national podiatric surgery audit tool PASCOM has a key role in determining patient satisfaction with service received and outcomes. The study aim was to examine the effects of time after surgery on satisfaction scores, by undertaking a retrospective longitudinal study utilising the patient satisfaction questionnaire known as the PSQ-10. A secondary objective was to examine test retest reliability, since this has not been previously reported. METHOD: NHS and private patients having undergone forefoot surgery were sent a further PSQ-10 satisfaction questionnaire after the standard 6-month PSQ-10 had been completed. The main outcome measure reflected a change in the score between the original and repeat PSQ-10 response. Internal consistency was measured by correlation between baseline questions for a subset of patients who were sent the second questionnaire within 6 months of the first. RESULTS: Of a total cohort of 204 patients, no significant differences were seen in overall scores. 46% showed increased satisfaction at the stage of the repeat questionnaire, with 41% a decline in score and 13% no change. Neurectomy patients improved the most with time and digital surgery was associated with the greatest decline in score. Significant correlations were demonstrated between all baseline questions for the test-retest cohort (13 patients). CONCLUSION: Time does not significantly influence patient satisfaction after discharge. There was satisfactory consistency between PSQ-10 responses. Further investigation into digital procedure outcomes is required. PMID- 20307416 TI - A year of foot and ankle orthotic provision for adults: prospective consultations data, with patient satisfaction survey. AB - OBJECTIVES: To characterise 12 months' adult, foot and ankle orthotic out-patient consultations in a regional centre; and to survey patients regarding their satisfaction with services received. METHODS: Prospective survey questionnaires completed by: (1) orthotists, during consecutive clinic consultations (n=4402 representing 2494 patients); (2) all patients receiving foot or ankle orthoses (n=1469), mailed 5 weeks later. Questions included a standard foot pain item, patients' perceived usefulness of the orthosis, and satisfaction with services received. Logistic regression identified factors associated with patients finding their orthosis 'very' or 'fairly helpful'. RESULTS: Consultations addressed myriad foot, ankle or other conditions. EVA (soft) foot orthoses were most commonly prescribed. The response rate from patients was 72%. Most (73%) said their orthosis would be 'very' or 'fairly helpful'. Following adjustment, females were less likely than males to find orthoses helpful (OR 0.71, p=0.031). All older age groups were at least twice as likely to find orthoses helpful as patients aged <40 (p<0.01). Ninety percent of respondents were 'very' or 'fairly satisfied' with the service received. CONCLUSIONS: Women, younger patients and those with more severe pain were less likely to perceive benefit from foot and ankle orthoses than other groups and may therefore require adjuvant or alternative intervention. PMID- 20307417 TI - The relationship between the height of the medial longitudinal arch (MLA) and the ankle and knee injuries in professional runners. AB - BACKGROUND: Usually the rate of lower extremity's injuries in sports such as running is known to be correlated with the height of foot arches. Foot pressure measurement studies have shown controversial results in this issue, mainly due to the complexity of the foot structure. This study aimed to investigate if any relationship exists between the MLA height and the ankle/knee injuries in professional runners. It was also aimed to find out any association between the foot pressure patterns and the clinical navicular drop test in the subjects. MATERIALS AND METHODS: Forty-seven professional runners were participated in this study and using the clinical navicular drop test, they were categorized into normal, low and high arch foot subjects. Using an Emed pedography platform (Novel, Germany), the maximum force, peak pressure and the contact area of their feet were studied in both static (single limb support) and dynamic conditions. RESULTS: The results of this study showed no strong correlation between the height of MLA and the rate of the ankle/knee injuries (P=0.58). The correlation between the clinical navicular drop test and the modified arch index (MAI) was between 0.32 in static and 0.57 in dynamic tests. CONCLUSION: The results of this study conveyed that having a lower or higher than a normal MLA is not a definite risk factor for sports-related injuries. This might be due to the complexity of the foot structure and its ability to accommodate with new situations routinely occurs in sport. Furthermore, although a high correlation was not found between the clinical navicular drop test and the foot pressure indices, due to the clinical entity of this test, the obtained association is relatively good. A significant correlation was found between the foot pressure distribution in single limb support (static) and the dynamic conditions, which provides an extrapolation of the results of this type static condition tests to the dynamic conditions. PMID- 20307418 TI - Diagnostic significance of radiologic measurements in posterior heel pain. AB - BACKGROUND: Posterior heel pain is a common complaint in both athlete and non athlete. For diagnosis of etiology certain angles, lines and soft tissue parameters have been developed in the literature to describe the calcaneal prominence and its relationship to Achilles tendon and its bursae. OBJECTIVES: A prospective study was undertaken to evaluate the diagnostic values of these angles, lines and soft tissue parameters in posterior heel pain. MATERIALS AND METHODS: Seventy-one painful heels in 58 patients (30 males and 28 females, mean+/-S.D. age; 41.4+/-10.82 years) were clinically and radiologically examined. This was compared with 50 heels in 25 control subjects. A lateral weight bearing film of the foot was taken to calculate different angles, lines and soft tissue parameters mentioned in the literature. RESULTS: There were 45 Pavlov's parallel pitch line positives and using test of Denis and Huber-Levernieux in only one posterior superior crest extended beyond vertical tangential. There was only one heel with Fowler & Philip angle >75 degrees. There were 10 heels with Steffensen & Evensen angle >65, 5 heels with total angle >90 degrees and 52 heels with Chauveaux-Liet angle >12 degrees. There were 73% true positive for Chauveaux-Liet angle and 63% true positive for parallel pitch line. Among soft tissue parameters ill defined retrocalcaneal recess was present in 61 symptomatic heels, plantar spur in 42 heels, posterior calcaneal step in 33 heels, Achilles tendon calcification in 29 heels, superficial tendo-Achilles bursitis in 58 heels, posterior calcaneal spur in 31 heels and antero posterior diameter of tendo Achilles more than 9 mm in 68 symptomatic heels. CONCLUSION: Parallel pitch lines, Chauveaux-Liet angle, ill-defined retrocalcaneal recess, superficial tendo Achilles bursa and anteroposterior diameter of Achilles tendon more than 9 mm about 2 cm above insertion are reliable objective diagnostic indicators of bony deformity of calcaneus and soft tissue affection in patients with posterior heel pain. It is the combination of these bony and soft tissue parameters, which enhance the diagnostic certitude. PMID- 20307419 TI - Foot pressure in clubfoot--the development of an objective assessment tool. AB - BACKGROUND: There are no universal criteria for the assessment of clubfoot. The ideal method should assess functional deformity reliably and objectively. Biomechanical techniques have also been suggested but their role remains undefined. OBJECTIVE: This study aimed to assess surgically corrected clubfeet by biomechanical means with the intention to develop certain ratios to aid in objective assessment. METHODS: Thirteen children (16 feet) with idiopathic clubfoot, who had previously undergone surgery (lateral-posteromedial release), were reviewed. Various clinical measurements were collected and symptoms assessed using a specially designed questionnaire. Biomechanical (foot pressure) parameters were obtained using two systems: Podotrack and Dynamic Pedobarograph. RESULTS: The results showed that foot pressure data were able to demonstrate abnormalities in foot posture and pressure distribution, which could objectively identify clubfoot deformities. In particular, ratios were calculated, which could be used to determine severity and monitor progression. CONCLUSION: This study suggests that foot pressure analysis should be routinely used in the assessment of clubfoot. The ratios calculated would be of immense help to the clinicians in monitoring the success of treatment and for early prediction of relapse in patients treated for clubfoot. PMID- 20307420 TI - The function of the midtarsal joint: a review of the literature. AB - The midtarsal joint (MTJt) consists of the combined articulations of the talonavicular and calcaneocuboid joints and represents the functional articulation between the rearfoot (talus and calcaneus) and the midfoot (navicular and cuboid). The movement of the transverse tarsal region has been described as a segment rotating around two distinct axes of the MTJt; the longitudinal and the oblique. Recent research has suggested that the two axes model of the MTJt is a theory of convenience to explain clinical observation, and that the MTJt moves in a more complex manner. It has been hypothesised that the MTJt has one triplanar axis of motion, so there remains the need to investigate the practical application of this understanding in terms of how this motion affects the MTJt in gait and the implications this may have on podiatric treatment. PMID- 20307421 TI - Gaenslen's split-heel incision for calcaneal osteomyelitis--case report. AB - BACKGROUND: The purpose of the report was to present a 45-year-old lady who had a chronic osteomyelitis right calcaneum with a large non-healing ulcer and discharging sinus, treated by split-heel incision of Gaenslen. OBJECTIVES: Patients who have a recurrent ulcer of the heel often have a below-the-knee amputation because durable soft tissue coverage cannot be obtained over the calcaneus. Often, even if the ulcer heals satisfactorily or the area appears to be revascularized as a result of a peripheral vascular procedure, the resulting surface is not durable and the ulcer recurs. Gaenslen's technique is recommended for refractory cases or patients with a draining sinus centrally located on the plantar aspect of the heel. An excellent functional result can be obtained. METHOD: Calcaneum was divided from posterior to anterior with a broad osteotome and split into two halves to expose the interior of the bone. Sequestra, infected material, necrotic slough damaged cortex were removed. The wound was closed loosely with a drain in situ. RESULT: The pressure sore and the surgical wound healing were remarkable at the end of 6 weeks. The heel had a deeply situated surgical scar and over which the surrounding tissues were laid, thus forming thick cushions. CONCLUSIONS: Split-heel incision of Gaenslen removed all sequestra, obviously infected matter and did little damage to the cortex. The resultant scar was painless and was so deeply situated that the tissues on either side curl inward to form 'cushions'. PMID- 20307422 TI - A case of pseudoarthrosis of the lateral talar process and distal fibula in a professional athlete. AB - We report a case of osteoarthritis of a pseudoarthrosis between the tip of the fibula and the lateral process of the talus. This was treated by excision of pseudoarthrosis with lateral ligament reconstruction. PMID- 20307423 TI - Re: Anomalous tibialis posterior muscle. PMID- 20307424 TI - Re: A clinical longitudinal evaluation of pre-fabricated, semi-rigid foot orthoses prescribed to improve foot function by Springett et al. [Foot 17 (2007) 184-189]. PMID- 20307425 TI - First MTP joint arthrodesis for the treatment of hallux rigidus: results of 29 consecutive cases using the foot health status questionnaire validated measurement tool. AB - BACKGROUND: Arthrodesis of the first MTP joint is an accepted and long established joint destructive procedure for the management of hallux rigidus. OBJECTIVES: This paper presents the results of 29 consecutive first MTP joint arthrodesis procedures for the treatment of hallux rigidus. METHOD: The outcomes of 29 (18 female and 11 male) consecutive arthrodesis procedures were analysed with the Foot Health Status Questionnaire (FHSQ), minimal important difference scores, and a patient satisfaction questionnaire. RESULTS: FHSQ foot pain scores improved for 27 (93%) patients; foot function improved for 23 (79%) patients; shoe scores improved for 18 (62%) patients; foot health improved for 20 (68%) patients; general health improved for 12 (41%) patients; physical activity improved for 21 (72%) patients; social capacity improved for 21 (21%) patients; vigour improved for 15 (51%) patients. FHSQ minimal important difference scores were achieved for foot pain in 25 patients (86%); foot function in 17 patients (58%); and general foot health in 19 (65%) patients. Analysis with the matched pairs Wilcoxon rank sum test (p<0.05) revealed statistically significant improvement in all FHSQ domains. Female patients appeared to fare better than male patients in all FHSQ categories other than general health and vigour. CONCLUSION: Arthrodesis of the first MTP joint can reliably reduce pain relating to hallux rigidus and can improve foot function and allow a return to physical activity. PMID- 20307426 TI - Arthrodesis of the first metatarsophalangeal joint for hallux rigidus--optimal position of fusion. AB - BACKGROUND: Good results are usually reported after arthrodesis of the first metatarso-phalangeal joint, but there is no definite agreement concerning the position that provides the best result. METHODS: We reviewed 35 patients with 39 fusions of the first metatarso-phalangeal joint 8 (2-15) years after surgery. In addition to clinical evaluation we measured the position of the arthrodeses radiographically and clinically, and also the distribution of pressure under the foot using insoles with pressure sensors. RESULTS: A total of 28 of 39 cases had an AOFAS score of 75 or better (90 best possible). Almost all patients experienced pain relief. Union was observed in 31 out of 39 feet, but the satisfaction rate was not significantly lower in those with pseudarthrosis. There was no strong correlation between the arthrodesis position and patient satisfaction. There was a good correlation (r=0.8; p<0.001) between the weight bearing radiographic extension angle and the height between the plantar surface and the pulp of the hallux and a flat board manually pressed against the sole of the foot. There was significantly increased local pressure under the pulp of the great toe in operated feet. CONCLUSIONS: There is only a weak correlation between position and clinical outcome. A good estimate of the extension angle is made by measuring the height between a flat object placed under the foot and the pulp of the distal phalanx. PMID- 20307427 TI - Treatment of tinea pedis with socks containing copper-oxide impregnated fibers. AB - BACKGROUND: Tinea pedis, known as Athlete's foot, is a common fungal infection of the feet, the majority of cases caused by dermatophytes. Copper oxide has potent antimicrobial and antifungal properties. OBJECTIVE: A pilot study designed to examine the efficacy of treating tinea pedis utilizing copper-oxide impregnated fibers woven into socks worn on a daily basis. METHODS: Fifty-six patients, ranging in age from 21 to 85 years were clinically diagnosed, photographed, and treated with the copper soled socks. Eight variables were studied, including scaling, erythema, fissuring, burning or itching, vesicular eruptions, edema, odor, and drainage. RESULTS: In a 9-day average follow up, all patients showed improvement or resolution of erythema (with a 95% Confidence interval (CI) of 1.0), fissuring (CI=1.0), vesicular eruptions (CI=1.0), scaling (CI=0.9-1.0) and for burning and itching (CI=0.61-0.95). In a 40-day average follow up, the 95% CI for improvement or resolution of scaling was 0.68-0.97, for erythema, 0.65-0.97, and for fissuring, burning and itching and vesicular eruptions it was 1.0. None of the study subjects worsened or showed adverse reactions while wearing copper oxide impregnated socks. CONCLUSION: This study strongly supports the effectiveness in using copper-oxide impregnated polyester fibers in treating the common manifestations of tinea pedis. PMID- 20307428 TI - What is the best method for child longitudinal plantar arch assessment and when does arch maturation occur? AB - BACKGROUND: The medial longitudinal arch modifies significantly during growth. Nevertheless, authors differ on the age at which the foot acquires the adult-like shape. The best method to assess this arch in children is also controversial. OBJECTIVES: Characterize the longitudinal arch of children between 3 and 10 years and compare the applicability of five evaluation methods. METHODS: Plantar prints were acquired from 391 healthy preschools children from the University of Sao Paulo, Brazil. We calculated the arch indexes of: Cavanagh and Rodgers, Chipaux Smirak, Staheli and the Alfa Angle, and compared them with the feet posture assessment. Non-parametric tests were used to compare among methods and ages. Spearman correlation was used to establish relationships among indexes. RESULTS: 3 and 4 years old showed a high prevalence of low arches (36-86%). Between 4 and 5 years old, significant difference was observed for all indexes. The indexes presented good correlation among them, although the proportions of the different arch types were different for each age group (p<0.001). CONCLUSIONS: The longitudinal arch acquires an adult-like shape progressively, being statistically notorious the moment of medial longitudinal arch's formation between 4 and 5 years old. The Chipaux-Smirak Index is the best index to assess children's feet; it provides a better classification for lower arches and is easily calculated. PMID- 20307429 TI - The MOJE total joint arthroplasty for 1st metatarso-phalangeal osteoarthritis: a short-term retrospective outcome study. AB - BACKGROUND: Evidence regarding the efficacy of the MOJE ceramic press fit total joint replacement for the first metatarso-phalangeal joint (MTPJ) is lacking. OBJECTIVES: Our aim was to assess the clinical outcome for the MOJE arthroplasty in a single surgeon series using objective and subjective assessment tools. METHODS: A retrospective outcome study of 24 implants was performed in 22 patients undergoing first MTPJ replacement for osteoarthritis from 2004 to 2006. Each patient underwent clinical assessment using the American Orthopaedic Foot and Ankle Score (AOFAS) for the hallux and a patient outcome satisfaction questionnaire. All pre- and post-operative radiographs were reviewed. RESULTS: Average follow-up was 26 months with a median AOFAS score of 80 out of a maximum 100. The revision rate at 3 years was 12.5%. Only 63% of patients were 'very satisfied' with the overall outcome from the procedure. AOFAS for the hallux correlated strongly with patient satisfaction. Radiographical mal-alignment in four patients was significantly associated with lower AOFAS (p=0.01). CONCLUSIONS: This implant offers less reliable outcomes than the 'gold standard' arthrodesis and one would advise caution regarding its use for osteoarthritis of the first MTPJ. PMID- 20307430 TI - A prospective comparison of two treatment options for tuberosity fractures of the proximal fifth metatarsal. AB - BACKGROUND: Tuberosity 'avulsion' fractures of the proximal fifth metatarsal are common injuries, but with few comparisons of conservative treatment options. OBJECTIVE: This study prospectively compared two commonly used conservative treatment methods. METHODS: 37 patients were allocated to treatment in either a plaster slipper (n=20) or tubi-grip support (n=17) for a period of 6 weeks. Patients were assessed at 2, 6 and 12 weeks after injury using a modified foot score which measured the level of pain and dysfunction. A radiograph was taken at 12 weeks. A Mann-Whitney U test compared median foot scores between the treatment groups at each review (p-value of 0.05 or less was deemed significant). RESULTS: A significantly (p=0.02) better foot score was measured in the plaster group at 2 weeks after injury (median score 68 (plaster group) compared to 57 (tubi-grip group)). However by the 6- and 12-week stages, the scores were comparable. Radiographs indicated two patients in each group with no clear evidence of union after 12 weeks. One patient remained symptomatic and required surgical treatment. CONCLUSIONS: The eventual clinical and radiological outcomes were comparable. During the initial 2 weeks, patients treated in plaster had a better-combined level of pain and function. PMID- 20307431 TI - Evaluation of surgical experience and the use of an osteotomy guide on the apical angle of an Austin osteotomy. AB - BACKGROUND: Distal osteotomies of the first metatarsal are commonly used to correct hallux valgus deformities. Of the distal osteotomies, the Austin osteotomy is popular among foot surgeons on an international level. The precision of the osteotomy is important to achieve a congruous osteotomy. OBJECTIVES: The purpose of this study was to examine the effects of experience and technique on creating a precise Austin osteotomy. METHOD: Three individuals with varying levels of experience (student, resident and podiatric physician) created Austin osteotomies in metatarsal sawbones, using three different techniques (freehand, guide wire and osteotomy guide). The medial and lateral apical angles were measured, and the mean, standard deviation, and range of the angles were calculated. The differences between medial and lateral angles were also calculated. RESULTS: The results indicated that the mean and range of the angles varied considerably with the freehand and guide wire techniques at all experience levels. The angles were accurate and consistent for all experience levels; however, when an osteotomy guide was used. The use of an osteotomy guide also noticeably reduced the number of divergent and convergent osteotomies. CONCLUSIONS: The use of an osteotomy guide consistently resulted in a more precise Austin osteotomy for all experience levels. PMID- 20307432 TI - Is eccentric muscle contraction a significant factor in the development of chronic anterior compartment syndrome? A review of the literature. AB - INTRODUCTION: The purpose of this article was to review published articles investigating the association of eccentric contractions of the anterior compartment with an increase in intramuscular pressure. METHODS: An electronic review using Medline, Amed and Science Direct returned 49 papers, seven of which were considered suitable. Manually browsing reference lists of these led to the identification of a further five relevant papers. A further nine papers were considered as suitable for background reading. RESULTS: Results of previous studies have indicated that there is a relationship between excessive eccentric contractions, delayed onset of muscle soreness, and an increase in intramuscular pressure. However, due to the differences in a number of variables between these studies a direct comparison cannot be made. CONCLUSION: Eccentric contractions of the anterior compartment have, in the short term, been associated with an increase in intra-compartmental pressure and delayed onset of muscle soreness in studies on healthy volunteers. There is no evidence as yet that there is a further association with the development of chronic anterior compartment syndrome. The long term effect of excessive eccentric contraction is believed to be a reduction of compliance in and loss of elasticity of the fascia, which is probably irreversible. PMID- 20307433 TI - Metastatic gastric adenocarcinoma mimicking osteomyelitis of second toe. AB - Recurrence of gastric carcinoma most frequently involves abdominal distension and usually occurs with in 5 years of primary surgery. Recurrence more than 8 years after surgery is extremely rare and bony metastasis occurs only in 0-17% cases of gastric carcinoma. We present a case of metastasis to the second toe which occurred 12 years after the initial surgery. The case highlights the importance of high index of suspicion of pedal metastasis in patients presenting with swelling or bony tenderness with history of carcinoma. PMID- 20307434 TI - Tarsal tunnel syndrome associated with a neurilemoma in posterior tibial nerve: a case report. AB - Compression neuropathy of the posterior tibial nerve (PTN) and its branches in the tarsal tunnel is called tarsal tunnel syndrome (TTS) and has various aetiologies. Space-occupying lesions in the tunnel, such as neurilemomas, can cause such a disease. When a neurilemoma occupies the tarsal tunnel, it can compress the PTN directly or indirectly and results in restriction of the tunnel volume. Symptoms due to this restricted volume may vary in TTS. A case of neurilemoma of PTN in tarsal tunnel with a complaint of posteromedial ankle intermittent pain in a 20-year-old patient is presented here. A mass was observed at the ankle posteromedially during clinical examinations and the patient underwent magnetic resonance imaging (MRI) and radiological investigation. Radiographic evaluation of the ankle was normal. However, MRI was revealed a mass adjacent to the PTN in the tarsal tunnel. An ovoid, smooth-surfaced, encapsulated and eccentrically localized mass in the PTN was detected at surgery. The mass was excised from the nerve and pathological evaluation revealed a neurilemoma (schwannoma). Neurilemomas arising from the PTN in the tarsal tunnel should always be kept in mind as a differential diagnosis when a patient complains of a posteromedial ankle pain. Since it is a space-occupying lesion and encapsulated tumor in the tarsal tunnel, simple surgical resection is curative without a distinct morbidity. PMID- 20307435 TI - Proper shoe sizes for Thai elderly. AB - BACKGROUND: Problems from improper shoe fitting are common, but there are limited foot data for the older Thai population. OBJECTIVES: To study foot dimensions and determine proper shoe sizes for Thai elderly. METHODS: Healthy older people: 108 men, 105 women, aged 60-80 years, who were independent in walking, were recruited. Thirteen foot dimensions and current shoes used were measured. Side-to side, gender difference, and correlations of main foot measurements were analyzed. RESULTS: About 50% women and 34% men wore too narrow shoes, and this was found to be associated with foot pain. At the same foot length (FL), men had larger foot width (FW) and toe depth. Foot width=2.39+(0.29 x FL), r=0.50, p=0.001 for women and=2.48+(0.31 x FL), r=0.56, p=0.002 for men. Arch length=1.0+(0.7 x FL), r=0.93, p=0.001 for both genders. Toe depth had constant values in all shoe sizes of each gender. Correlations of other foot parameters were reported. CONCLUSIONS: These anthropometric data is essential for proper shoe fitting in order to provide foot ergonomics and prevent foot problems for older Thai people. PMID- 20307437 TI - Association of abnormal foot angles and onychocryptosis. AB - OBJECTIVES: To find if there is any association between the abnormal interphalangeal (IPA) and/or hallux valgus angles (HVA) and onychocryptosis. MATERIALS AND METHODS: Eighty consecutive patients with proven ingrowing toenail of all grades had their interphalangeal and hallux valgus angles of the great toe been measured on a stress view standing radiograph, and compared with a control group of normal people. RESULTS: The mean age (SD) of our patients was 20 (6.4) years. Males are affected more than females. Lateral edge ingrowing was found in 85% of patients. The percentage of abnormal HVA in the diseased toes (60%), was significantly higher than that in contralateral toes (30%) (p<0.0005) and in normal controls (12%) (p<0.0005). Similarly, the percentage of abnormal IPA in the diseased toes (85%) was significantly higher than that in the contralateral toes (50%) (p<0.0005) and in normal controls (25%) (p<0.0005). CONCLUSIONS: Abnormal interphalangeal and hallux valgus angles or lateral deviation of the distal phalanx significantly associated with onychcryptosis. PMID- 20307436 TI - Local anaesthetic toxicity. AB - BACKGROUND: Local anaesthesia has been used by British podiatrists since the early 1960s. The use of local anaesthesia has allowed for the advancement of scope of practice and the development of podiatric surgery. Local anaesthesia is however associated with potential risks and adverse reactions including toxicity. OBJECTIVES: To review the current literature on the subject of local anaesthetic toxicity and to consider recent developments in the management of acute toxicity. CONCLUSIONS: Local anaesthesia although safe has the potential to cause serious harm in the event of toxicity. Appropriate steps should be taken to minimise the risk of toxicity and should it occur measures should be applied to minimise the consequences of toxicity. Such measures may include the use of Intralipid for resuscitation. PMID- 20307438 TI - The status of podiatry in the United Kingdom. AB - This paper reviews the sources of professional status and analyses these in relation to the podiatry profession in the United Kingdom. It is argued that the nature and act of professional practice and the patient/professional relationship are of particular importance in defining the status of the profession. These effects are discussed in relation to podiatry and compared to a high status professional group, that of dentistry. Finally the effects of attempting to change professional status are discussed. PMID- 20307439 TI - A review of surgical outcomes of the Lapidus procedure for treatment of hallux abductovalgus and degenerative joint disease of the first MCJ. AB - BACKGROUND: The modified Lapidus procedure has been used to treat hallux abducto valgus and degenerative joint disease of the first metatarsocuneiform joint for many years. Historically, the Lapidus has been associated with poor satisfaction due to complications such as non-union. The aim of this study was to review the surgical outcomes of 18 patients using the validated Foot Health Status Questionnaire (FHSQ). The four domains within the FHSQ were all investigated. Pre and post operative angular measurements were also reviewed. RESULTS: The results of the FHSQ were positive for all four domains, with foot pain having the greatest change. Only two complications were recorded: one poor pain control and one post operative bleed and all 18 patients went to osseous union. Radiographically the mean intermetatarsal angle improved by 7.8 degrees and HAV angle by 22.9. A positive association was also demonstrated between validated 'Minimal Important Difference' (MID) scores. CONCLUSION: The Lapidus is a valuable procedure that can have few complications and high levels of patient satisfaction. PMID- 20307440 TI - Audiovisual distraction as an adjunct to pain and anxiety relief during minor surgery. AB - BACKGROUND: Minor surgery for ingrown toenails can provoke anxiety and the anaesthetic injection can be acutely painful. Distraction techniques may reduce the associated pain and anxiety. OBJECTIVE: To investigate an audiovisual distraction (Bedscapes) on pain and anxiety during minor surgery for the correction of ingrown toenail. METHOD: In a randomised controlled trial, patients (N=152) with ingrown toenails requiring surgical correction under local anaesthesia were allocated to receive Bedscapes+standard care or standard care alone. Pain levels due to local anaesthetic injection were assessed post procedure, and anxiety levels were assessed pre- and post-procedure in both groups. Follow-up focus groups were conducted with 14 patients allocated to the Bedscapes group, and one-to-one interviews were held with four podiatrists. RESULTS: Participants with high pre-procedure anxiety scores experienced greater pain on injection, and older patients reported lower pain than younger patients, regardless of group allocation. Bedscapes did not reduce pain or anxiety, and was apparently no more effective than interpersonal interaction between podiatry staff and the patient. CONCLUSIONS: Pain of injected anaesthesia correlates closely with pre-operative anxiety. Formal audiovisual distraction has no added benefit over interpersonal interaction in the alleviation of pain and anxiety in patients undergoing nail surgery. PMID- 20307441 TI - Effect of using truncated versus total foot length to calculate the arch height ratio. AB - OBJECTIVE: The purpose of this study was to determine the arch height ratio in a large cohort of subjects as well as to assess the reliability and validity of the foot measurements utilized in the study. METHOD: Eight hundred and fifty subjects, 393 women and 457 men, consented to participate in the study. The dorsal arch height, total foot length, and the truncated foot length were used to calculate two variations of the arch height ratio. In addition to determining within- and between-rater measurement reliability, radiographs were used to establish validity. RESULTS: The truncated arch height ratio can be estimated using the total foot length, unless toe deformities are present in the individual being assessed. All foot measurements had high levels of intra- and inter-rater reliability and the validity of measuring the dorsal arch height while standing with equal weight on both feet was established. CONCLUSIONS: This investigation provides normative values from a large cohort of healthy female and male subjects for two variations of the arch height ratio. The arch height ratio is a reliable and valid measurement that may prove useful to clinicians and researchers for the classification of foot posture. PMID- 20307442 TI - The effect of different skin-ankle brace application pressures with and without shoes on single-limb balance, electromyographic activation onset and peroneal reaction time of lower limb muscles. AB - BACKGROUND: Several studies have been carried out in order to investigate the effect of ankle bracing on ankle joint function and performance. However, no study so far has examined the role of skin-brace interface pressure in neuromuscular control. The aim of this study was to investigate the effect of different skin-ankle brace interface pressures, with and without shoes, on quiet single-limb balance and the electromyographic (EMG) activation sequence of four lower limb muscles. METHODS: Twelve male physical education students who volunteered to take part in the study were measured with and without shoes under three ankle brace conditions: (i) without brace, (ii) with brace and 30 kilopascals (kPa) application pressure and (iii) with brace and 60 kPa application pressure. Single-limb balance (anteroposterior and mediolateral parameter) was assessed on the dominant lower limb, with open and closed eyes, on a force platform, simultaneously with the EMG recording of four lower lower limb muscles' (gastrocnemius, peroneus longus, rectus femoris and biceps femoris) activation onset. Peroneus longus reaction time was also measured by provoking a sudden subtalar inversion stress test using a trap-door. RESULTS: The results showed that the application of athletic footwear resulted in a significant difference between the condition with shoes and without shoes, with a significantly increased anteroposterior sway and sway velocity, in all three ankle brace application conditions with shoes (F=50.9, d.f.=1, p<0.001 and F=58.4, d.f.=1, p<0.001), but had no effect in the mediolateral stability, or the total stability parameter. Shoes had no significant effect on the EMG activation sequence of the four lower limb muscles. Lastly, ankle brace application with 30 and 60 kPa application pressures, with and without athletic footwear, led to a significant delay in the peroneus longus reaction time (F=9.71, d.f.=2, p<0.001). CONCLUSIONS: These findings suggest that different ankle brace application pressures may have an effect on single-limb balance, and peroneal reaction time. The application of athletic footwear, further adversely affects these parameters significantly. Further research is needed in this area with more dynamic and functional measurements, before the safe use of ankle bracing can be widely recommended. PMID- 20307443 TI - Acute effect of orthoses on foot orientation and perceived comfort in individuals with pes cavus during standing. AB - BACKGROUND: Changes in foot orientation due to orthoses and the relationship with perceived comfort are still unclear in pes cavus. The purpose of this study was to determine the acute changes of fore-foot angles due to the use of custom-made orthoses and their relationship with perceived comfort during standing. METHODS: Two photographs were taken using a color-coded camera-based system from the posterior and medial views of 20 subjects with bilateral pes cavus under barefoot and with orthoses conditions during standing. Djian-Annonier, calcaneal inclination, 1st metatarsal declination and rearfoot angles were measured and perceived comfort in the forefoot, midfoot and rearfoot was estimated using an adapted Visual Analogue Scale-type questionnaire. RESULTS: In comparison with the barefoot condition, orthoses increased significantly the 1st metatarsal declination angle by 1.9 degrees (p<0.01), and the Djian-Annonier angle by 1.1 degrees (p=0.02). The calcaneal inclination angle decreased significantly by an average of 3.0 degrees (p<0.01). Wearing orthoses significantly improved perceived comfort in forefoot, midfoot and rearfoot when compared to barefoot condition (p<0.01). A significant correlation was observed between variation of calcaneal inclination angle and the perceived comfort at the midfoot (r=-0.44; p=0.04). CONCLUSION: Flattening of foot arch and improvement of midfoot perceived comfort in pes cavus could be attributed to the reduction of the calcaneal inclination angle in the sagittal plane by using orthoses during standing. PMID- 20307444 TI - Cross-sectional study to evaluate radiological parameters in hallux rigidus. AB - BACKGROUND: Hallux rigidus (HR) is a common condition with X-rays used to evaluate its pathology, grade joint changes and to inform treatment. METHOD: A cross-sectional study was undertaken to evaluate radiological foot parameters in HR. In 110 subjects (180 feet) aged 18-70 years (mean 52 years) standard weight bearing X-rays were examined using dorsal plantar and lateral views. RESULTS: Seventy (64%) subjects had bilateral HR and 73 (66%) were female. The mean onset of HR (denoted by first metatarsophalangeal (MTP) joint restriction/pain) was 44 (14-68 years) years and median HR duration was 6 years (1-33 years). Flat or chevron-shaped metatarsal heads presented in 131 (73%) feet and a history of first MTP joint trauma in 22% (74% of whom had unilateral HR). In 74% of feet hallux abductus interphalangeus angle (HAI degrees) was greater than normal (< or =10 degrees). Correlations between first MTP joint narrowing and sclerosis (r=0.76, p=0.01) and increased HAI degrees and first MTP joint narrowing (r=0.34, p=0.01) was found. The mean hallux equinus angle of 11 degrees was outside the normal range (16-18 degrees). Abnormal sesamoid morphology presented in 117 (65%) feet (30% irregular or hypertrophic). Proximal sesamoid displacement was greater than that seen in non-HR. Metatarsus primus elevatus was within normal range (< or =8 mm) in 160 (89%) feet. The first metatarsal was longer than the second metatarsal in 66 (37%) feet although the first metatarsal was longer than the third metatarsal in 131 (73%) feet and may be responsible for altered forefoot function in HR. CONCLUSIONS: HR was associated with female gender, bilateral involvement, older age groups, flat or chevron-shaped metatarsal head, longer proximal phalanx, increased HAI degrees and a first metatarsal longer than the third metatarsal. For radiological parameters to be considered valid for inclusion in a classification of HR their content validity needs to be established by formal research. PMID- 20307445 TI - Foot and ankle injuries and time lost from play in professional soccer players. AB - BACKGROUND: Ankle and foot injuries are common in professional soccer players, but the relation among diagnosis, severity and time lost from play is not well known. OBJECTIVE: The aim of this study is to investigate the relationship among diagnosis, injury severity and time lost to play of professional soccer players with severe ankle and foot injuries with reviewing the recent literature. DESIGN: Retrospective descriptive study. PATIENTS AND METHODS: Collected data of 66 players with severe ankle and foot injuries were included in the study. Type of injury, diagnosis, treatment, injury severity and finally, time lost from play were evaluated from the medical records. Injury severity ('severe' if >28 days, 'moderate' if between 8 and 28 days) and time lost from play were calculated from medical records and by telephone interviews with the players. RESULTS: Most injuries (n=20, 32%) occurred during player-to-player contact. The most common diagnosis was ankle sprain (30.3%) with anterior talofibular ligament injury. Most (55%) hindfoot injuries were Achilles tendinopathy with or without rupture. Treatment was surgical in 23 patients (35%). The mean time lost from play for players with severe foot and ankle injuries was 61 days (range 21-240 days); after Achilles tendon ruptures, the mean time lost was 180 days. Injury severity was severe (>28 days lost from play) in 64% patients and moderate (8-28 days lost from play) in 36% patients. CONCLUSION: Time lost to play can dramatically increase by the presence of severe ankle and foot injuries. Serious ankle and foot injuries in this study resulted in players being out of professional competition for about 2 months. PMID- 20307446 TI - Eversion and inversion muscle group peak torque in hyperpronated and normal individuals. AB - BACKGROUND: Excessive subtalar pronation causes significant changes in the biomechanics of the lower leg, adversely influences proprioceptive feedback and neuromuscular reflex behavior and consequently, affects stability of the foot. However, the changes in muscle strength, caused by hyperpronation are unclear. OBJECTIVES: The purpose of the present study was to compare the evertor and invertor peak torque between hyperpronated and normal individuals as well as between their dominant and non-dominant foot. METHOD: 20 healthy male participants volunteered for this study. Leg dominance was assessed on the basis of a questionnaire and navicular drop measurements were used to classify participants into two groups: hyperpronated (> or =10 mm) and normals (5-9 mm). Isokinetic concentric eversion and inversion muscle group strength was tested at 30 degrees and 120 degrees/s using the Con-Trex MJ isokinetic dynamometer. RESULTS: In all cases, inversion peak torque was greater than eversion peak torque and declined with increasing angular velocity. No significant differences were found for inversion and eversion concentric strength at both speeds tested, neither between normal and hyperpronated individuals neither between their dominant and non-dominant foot. CONCLUSIONS: These results indicate the need re evaluation of navicular drop values in order to identify normal and abnormal subtalar pronation. The assessment of eccentric contractions is also proposed when examining invertors and evertors isokinetic strength. PMID- 20307447 TI - Sever's disease--does it effect quality of life? AB - BACKGROUND: Sever's disease is a condition which has been described inconsistently in the literature with respect to pathology, aetiology and management. In particular, the impact of this condition has been overlooked, probably because it is usually self-limiting. METHOD: This study used a prospective comparative design study to determine the impact of Sever's disease on the quality of life of its sufferers. RESULTS: Three scales--Happiness, Satisfaction with symptoms and Pain/comfort scale--from the POSNA musculoskeletal questionnaire showed significant differences between the symptomatic and control groups. CONCLUSION: Although the condition may resolve with time, these results show that it has a considerable impact on children's lives. PMID- 20307448 TI - Optokinetic analysis of gait cycle during walking with 1 cm- and 2 cm-high heel lifts. AB - The use of orthotic heel lifts is proposed in many cases of Achilles tendon disorders as a first-line or conservative treatment. The use of heeled shoes induces a plantar flexion of the ankle joint with a consequent decrease in the tension forces acting onto the triceps surae. The question to address is how high must the heel be? Gait cycle using 1 cm- and 2 cm-high heel lifts was examined. Each measurement included kinetic and kinematic data on angular variation and moments and power at the hip, knee and foot. The study included 14 healthy subjects (5 males, 9 females) between 20 and 35 years of age. The data provided by the analysis of the force plate curve showed a statistically significant change in some parameters (plate forces, knee moments) which were deemed useful in the analysis of load transfer modalities. A very significant decrease (p=0.0001) was found in the amplitude of the curve expressing the force produced by the whole limb in response to ground reaction forces. This is expressed by a decrease in minimum values, suggesting a lower degree of energy absorption at heel strike, as well as maximum values reflecting the amount of energy generated at push off. This might suggest that by reducing energy absorption by the whole limb a 2-cm heel lift would have a protective effect for those muscles that are most significantly involved in this function, such as the tibiotarsal complex (triceps surae) and the knee complex (rectus femoris). PMID- 20307449 TI - Flat foot and femoral anteversion in children--a prospective study. AB - BACKGROUND: Flat foot in children during the first years of life evokes significant parental concern. Flat foot, intoeing and femoral anteversion may well be differential dimensions of developmental pathodynamics with potential for inter-related developmental correction. While correlation of femoral anteversion with intoeing is documented, its relationship with flat foot remains unclear. OBJECTIVE: The aim of this prospective study is to investigate the relationship between flat foot and internal rotation of hip, indirectly femoral anteversion. METHODS: 651 Children, 339 boys and 312 girls, aged 3-6 years, were examined and Contact Index II for flat foot as well as internal rotation of hip measured. 82 children with other foot and leg deformities were excluded from further analysis. RESULTS: Out of 569 children, 95 (16.7%) had flat feet--56 bilateral, 39 unilateral--with Contact Index II of 0.88 or above. All children with flat feet (and none of the normal 474) had raised internal rotation of hip (mean 69.9 degrees, range 62-80 degrees). CONCLUSION: Regression analysis established an unequivocal and highly significant statistical relationship between flat foot and increased internal rotation of hip (F=168.1, p<0.001, r=0.53) in children between 3 and 6 years. PMID- 20307450 TI - Achilles tendon rupture following coblation for insertional Achilles tendinosis. AB - Radiofrequency microdebridement for Achilles tendinosis is a relatively new technique. We report a case of Achilles tendon rupture in a patient eight weeks after coblation for his right insertional Achilles tendinosis. We believe that this is the first reported case of Achilles tendon rupture following this new treatment of radiofrequency microdebridement for chronic Achilles tendinosis. PMID- 20307451 TI - Adamantinoma of the calcaneum--a case report. AB - Adamantinoma is rare, representing less than 1% of all primary malignant bone tumours. It is a slow growing low grade malignant tumour which is often clinically, radiologically and histologically mistaken for many other tumours like Ewing's sarcoma, synovial sarcoma, fibrosarcoma, metastatic carcinoma, fibrous cortical defect and osteofibrous dysplasia. Adamantinoma commonly occurs in the tibia. It is also known to occur in the fibula, femur, humerus, radius and ulna. Adamantinoma of the foot is extremely rare. There are few reported cases of metatarsal and cuneiform bone involvement. To our knowledge adamantinoma of the calcaneum has not been previously reported in the literature. We report the case of a male patient, aged 33 years, who was treated for adamantinoma of the calcaneum and followed for 16 years highlighting the difficulty in diagnosis and management of this rare tumor occurring at a rare site. PMID- 20307452 TI - Secondary chondrosarcoma in an enchondroma in a proximal phalanx of toe. A diagnostic problem. A case report. AB - The authors present a case of secondary chondrosarcomatous transformation in enchondroma in toe. The authors have discussed the available literature to throw light on differentiation of benign and malignant form. PMID- 20307453 TI - Foot varus in stroke patients: muscular activity of extensor digitorum longus during the swing phase of gait. AB - BACKGROUND: Hemiparetic patients often present an abnormal leg muscles balance that can lead to foot deformities like equinovarus or varus. OBJECTIVE: To assess whether a muscle imbalance between tibialis anterior and extensor digitorum longus was associated with a varus deformity of the foot during the swing phase of gait in stroke patients. METHODS: Twenty hemiparetic patients presenting a foot varus during the swing phase of gait were compared to 16 healthy subjects. Gait was analyzed by video recording and by surface electromyography. Duration and magnitude of electromyographic signal were collected for tibialis anterior and extensor digitorum longus. Presence of an activity of the calf muscles during the swing phase was also evaluated. RESULTS: Hemiparetic patients exhibited more often premature activity of the calf muscles (p<0.05) and greater duration and amplitude asymmetry between tibialis anterior and extensor digitorum longus (p<0.05). These asymmetries were explained by a decrease in extensor digitorum longus activity (p<0.05). CONCLUSIONS: The activity of extensor digitorum longus muscle during the swing phase of gait is important to balance the foot in the frontal plane. The activation of that muscle should be included in rehabilitation programs. PMID- 20307454 TI - An evaluation of the long-term effects of total plantar fasciotomy--a preliminary study. AB - BACKGROUND: Plantar fascia release for chronic plantar fasciitis has given excellent pain relief and rapid return to activities with few reported complications. Cadaveric studies have led to the identification of some potential post-operative problems, commonly weakness of the medial longitudinal arch (MLA) and pain in the lateral midfoot. METHODS: Eight total plantar fasciotomy patients (five bilateral and three unilateral) were evaluated subjectively and objectively with regards to surgical outcome and biomechanical change. The centre of pressure (COP) and loading of the foot were measured using the F Scan mobile system and COM'nalysis software. In addition, five control subjects were evaluated with the F Scan. The reading for one foot of one of the control subjects was discarded due to a biomechanical abnormality. RESULTS: The results of this study were that the COP of the foot in post-total plantar fasciotomy subjects was significantly laterally deviated throughout the propulsive phase of gait compared to that of control subjects (p<0.05). There was no significant difference in plantar pressure at the rearfoot or the first metatarsophangeal joint (MTPJt) between the post-operative and control groups (p>0.05). Six of the eight of the post operative patients (11 feet) considered the procedure to be successful in resolving their symptoms. CONCLUSION: Total plantar fasciotomy may result in changes to the COP of the foot. It could be extrapolated from this data, in conjunction with subjective visual clinical observations of gait, that supination of the foot could occur post-operatively rather than the pronatory state secondary to a collapsed arch that, collectively, the results of cadaver studies have suggested. The conclusions drawn from this pilot study are to some extent speculative, as the measurements were only made post-operatively and a small number of subjects were studied. Further research is required in this area. PMID- 20307455 TI - Hallux rigidus: a cross-sectional study to evaluate clinical parameters. AB - BACKGROUND: Hallux rigidus (HR) is a common condition with history and physical examination used to help evaluate pathology, grade clinical changes and to inform treatment. METHOD: A cross-sectional study was undertaken to evaluate the demographics of and clinical parameters encountered in HR. In 110 subjects (180 feet) aged 18-70 years (mean 52 years) a standardized history and physical examination was undertaken. Clinical parameters associated with HR were evaluated. The Foot Health Status Questionnaire (FHSQ) was used to measure health related quality-of-life dimensions. RESULTS: Seventy (64%) subjects had bilateral HR and 73 (66%) were female. Mean HR onset was 44 (14-68 years) years and median HR duration 6 years (1-33 years). A history of 1st MTPJ trauma presented in 22% of subjects; 74% of whom had unilateral HR. Eighty-four (47%) feet had pes planus based on a positive Foot Posture Index. A correlation between pes planus and 1st MTPJ pain was found (r=0.84, p=0.05). In 74% of feet, hallux abductus interphalangeus angle (HAI degrees ) was greater than normal (< or =10 degrees ). A correlation between HAI and reduced 1st MTPJ ROM was found (r=0.92, p=0.05). Second toe length was the same as the hallux in 111 feet (62%). A correlation between valgus hallucal rotation and 1st MTP joint pain in HR was found (r=.78, p=.05). A positive relationship was found between 2nd toe length and 1st MTPJ pain (p=0.001<0.05). A correlation between hallucal interphalangeal joint (IPJ) hyperextension and 1st MTPJ pain was found (r=0.78, p=0.01). A positive relationship was found between lesser MTPJ pain and supination at propulsion (p<0.001). There was no evidence of Achilles tendon contracture. The FHSQ results concur with clinical findings. CONCLUSIONS: HR was associated with female gender, bilateral involvement, older age groups, increased HAI degrees, 2nd toe length similar to hallux, hallucal IPJ hyperextension, lesser MTP joint pain, flat foot and certain gait alterations. HR was not associated with Achilles tendon tightness or footwear. The content validity of clinical parameters of HR needs to be established by formal research prior to their inclusion in a classification of HR. PMID- 20307456 TI - Surgical treatment for calcaneal intraosseous lipomas. AB - Intraosseous lipoma is among rare benign tumors of the bone. The aim of the present study was to evaluate the long-term surgical results of calcaneal lipomas, representing a relatively rare localization for this type of tumors. The present study included 21 calcaneal lipoma cases (22 feet) referred to our podiatry clinic between 1991 and 2001 with complaints of foot and heel pain resistant to conservative treatment for the last 3-6 months. In all cases, the diagnosis of calcaneal intraosseous lipoma was first confirmed radiologically, then histologically. The mean age was 39 years (range 16-62), 15 were females (71%) and 6 were males (29%). One patient had bilateral disease, whereas 11 and 9 patients had right and left calcaneal involvement, respectively. None of the patients have a palpable mass in their foot. For pre-operative differential diagnosis, 3 patients had computerized tomography examination (CT scan) and 8 patients underwent magnetic resonance imaging (MRI). All lesions were totally curetted out with angled curettes. The defect was filled with cancellous autografts taken from the ipsilateral iliac crest. In only four patients, the amount of autograft was not sufficient, so a combination of cancellous allograft and autograft was used. No drain was used. An elastic bandage was wrapped around the foot and ankle, and cold packs were applied to the surgical site. The mean duration of follow up was 94 (45-143) months. Pain improved in 17 feet at 4 months, in an additional 4 feet at 8 months and in the remaining one foot at 12 months. The mean time to the graft consolidation was 5 months (range 3-7 months). There were no recurrences or pathological fractures during the follow up. No wound infection or necrosis was seen at the surgical sites. There were no neurovascular complications. Five cases experienced pain in the iliac bone for 1 month, due to grafting procedures. Although calcaneal intraosseous lipoma accounts for a small portion of cases in the huge differential diagnosis chart for foot pain, it should be kept in mind as a possible diagnosis in unresolved cases. Most of the patients would benefit from non-surgical treatments. But if this is not the case, surgical treatment is indicated. In conclusion, curettage and autogenous bone grafting is an easy and effective method for the surgical treatment of calcaneal intraosseous lipomas. PMID- 20307457 TI - Efficacy of tibial nerve block, local steroid injection or both in the treatment of plantar heel pain syndrome. AB - BACKGROUND: Plantar Heel Pain Syndrome (PHPS) describes centralised plantar heel pain and tenderness. It can account for up to 15% of referrals to clinicians involved in the treatment of foot pain. OBJECTIVE: To compare tibial nerve block, local infiltration with steroid or both combined in the treatment of PHPS. METHODS: Patients with PHPS were randomly assigned to three treatment groups: Group 1-steroid injection to heel; Group 2-local anaesthetic block to tibial nerve; Group 3-both procedures. Pain visual analogue scale (VAS) was measured at baseline and after 1, 6 and 26 weeks. Heel tenderness index (HTI) was measured at baseline and after 6 weeks. The patient rated their discomfort from the injection(s) using a VAS. RESULTS: Forty-five patients (27 female) were recruited, 14 in Group 1, 12 in Group 2 and 19 in Group 3. Median age was 55, disease duration was 10 months and baseline pain VAS was 7.0 cm. All groups experienced a sustained improvement in pain VAS between baseline and weeks 1, 6 and 26 (all p<0.0001). Group 1 reported significantly lower pain VAS that those in Group 2 (p<0.01) or Group 3 (p<0.05) at week 6. Group 2 found the procedure less uncomfortable than Group 1 (p<0.01). The HTI was significantly higher in Group 2 at 6 weeks compared to Group 1 (p<0.005) and Group 3 (p<0.05). CONCLUSIONS: This study suggests that the natural history of PHPS following an injection is encouraging, that a tibial nerve block reduces the discomfort of the procedure, that a steroid injection to the heel may accelerate improvement and that clinicians should consider a combination of both strategies. PMID- 20307458 TI - A report of UK experience in 917 cases of day care foot surgery using a validated outcome tool. AB - BACKGROUND: Day case surgery is an increasingly important treatment modality and one that foot surgery is particularly well suited to. OBJECTIVES: This article presents an in depth evaluation of the outcomes of day case foot surgery undertaken in the primary care setting. METHOD: 917 consecutive day surgery cases were evaluated with the Foot Health Status Questionnaire (FHSQ), patient satisfaction questionnaires and complication audits. RESULTS: 917 separate day care admissions were audited (696 females and 221 males). The average age at time of surgery was 50 years (range 14-100, S.D. 11). Post-operative follow up was usually complete by 26 weeks (range 21-218 weeks, S.D. 145). A total of 2772 individual procedures with patients receiving between one and five procedures per admission. The majority of patients (81%, N=743) opted for local anaesthesia. The FHSQ scores for foot pain, foot function, foot health, shoe fitting, general health, physical activity, social capacity and vigour improved. Patient satisfaction results were favourable and complication rates were within acceptable limits. CONCLUSIONS: Podiatric surgery is well placed to meet both the demands of government and patients in delivering a high quality, safe and efficient treatment for patients requesting elective surgical intervention for foot deformity. PMID- 20307459 TI - Fixation of an Akin osteotomy with a tension suture: our results. AB - An Akin osteotomy is a closing wedge varus osteotomy of the proximal phalanx, usually performed as part of a hallux valgus correction surgery to complement the metatarsal correction. Numerous fixation techniques have been described; most provide good and stable fixation, but involve permanent and sometimes protruding hardware. A retrospective cohort study has been carried out of 115 feet in 109 patients using a technique with an absorbable suture fixation of the medial cortex of the proximal phalanx while preserving the lateral cortex. All the osteotomies united completely with no loss of position. HV angles and IM angles were within acceptable parameters. In comparison to others methods, the technique presented in this study is technically simple, provides good results, requires no specialized instrumentation, is cost effective and has a very low complication rate. PMID- 20307460 TI - Use of the modified Stainsby procedure in correcting severe claw toe deformity in the rheumatoid foot: a retrospective review. AB - INTRODUCTION: In claw toe deformity, the plantar plate of the metarsophalangeal joint becomes displaced onto the dorsal aspect of the metatarsal head. The Stainsby procedure replaces the displaced plantar plate to its correct position beneath the metatarsal head. OBJECTIVE: In this study we assess the efficacy of a modified Stainsby procedure for the treatment of claw toe deformity. METHODS: Thirteen patients were operated on between 2002 and 2008. Eleven patients (13 feet) were available for review with the average follow-up period being 16 months. Clinical examination was performed and AOFAS forefoot scores were measured. RESULTS: All 13 (100%) of the feet operated on had severe or moderate pain preoperatively. None had significant pain at review. Plantar callosities were reduced from 13 (100%) feet preoperatively to 1 (9%) foot postoperatively. The AOFAS forefoot score in the eleven patients improved significantly by 40.7 points from a preoperative mean of 20.1 to a mean of 50.2 at review (p<0.001). Ten (91%) of the 11 patients were completely satisfied with the procedure, 1 patient was satisfied with some reservations. CONCLUSION: This study demonstrates the modified Stainsby procedure to be effective in correcting claw toe deformity in the rheumatoid patient. It relieves pain, skin callosities and improves overall forefoot function. PMID- 20307461 TI - Midfoot plantar pressure significantly increases during late gestation. AB - BACKGROUND: A rise in plantar pressure has been observed in pregnant women with foot pain. The current literature on plantar pressure in pregnancy is sparse. It has been postulated that changes in plantar pressure result from the physiological effects of pregnancy. In this study we aim to quantify the plantar pressure of women in late pregnancy. METHODS: Twenty-two pregnant women undergoing a caesarean section and twenty non-pregnant women were recruited from University Hospital Coventry and Warwickshire between May to June 2007. Plantar pressure measurements were performed using an in-shoe measurement system. The control group was compared with the pregnant group at 38 weeks gestation. A selection of the pregnant group had repeat measurements at 4 months post-partum. The pre and post-partum measurements were also compared. RESULTS: The pregnant group (PG) exerted a significantly higher mean midfoot pressure compared to the non-pregnant control group (CG) (PG=115.5kPa, CG=95.4kPa; p=0.001). Post-partum (PP), there was a significant reduction in the mean and maximum midfoot pressure (mean; PG=111.9kPa, PP=66.2kPa; p<0.001, maximum; PG=184.0kPa, PP=108.3kPa; p<0.001). CONCLUSIONS: The physiological changes in late pregnancy result in an increase in midfoot plantar pressure. This increase resolves post-partum. PMID- 20307462 TI - The light revival: does phototherapy promote wound healing? A review. AB - BACKGROUND: Throughout history, light has been recognised as a potential source of healing. The introduction of lasers made it possible to modify and control light for optimum therapeutic use. AIM: This paper reviews recent clinical trials that test phototherapy on human models in order to assess the value of phototherapy in routine wound care. METHOD: A literature search was undertaken using a variety of sources including online databases. RESULTS: The results of numerous in vitro and animal investigations suggest that phototherapy may stimulate cell activity and promote tissue repair. Reports of human clinical trials are relatively few. There is inconsistency of selected treatment parameters amongst studies testing the effect of phototherapy on wound healing. Clinical trials using human models do not provide sufficient evidence to establish the usefulness of phototherapy as an effective tool in wound care regimes. CONCLUSION: Further well designed research trials are required to determine the true value of phototherapy in routine wound care. PMID- 20307463 TI - Simultaneous bilateral fracture-dislocation of the talus: a case report. AB - A bilateral talar body fracture-dislocation in a 29-year-old multitrauma patient is presented. There was a comminuted fracture associated with an ankle, subtalar and talonavicular subluxation on the right lower limb and an open fracture with complete dislocation of the body of talus on the left side. We performed a minimal invasive reduction and stabilization of the fractures with the use of K wires, due to severe contamination of the wounds and the patient's poor general condition. After a 28-month follow-up there were signs of posttraumatic arthritis but no signs of avascular necrosis of the talus bilaterally. The range of motion in both ankle joints was limited but the patient had a satisfactory level of activity. PMID- 20307464 TI - Bizarre accessory metatarsal located between the left fourth and fifth metatarsals: a case report. AB - We report a case of bizarre accessory metatarsal located between the left fourth and fifth metatarsals without a supernumerary digit in a 6-year-old girl. The accessory metatarsal was resected to alleviate foot pain on walking. This metatarsal dysplasia might have arisen from sequential failures of digital formation at an early stage of development. PMID- 20307465 TI - Neuro-epiphyseal injury around the ankle: a case report. AB - An epiphyseal injury without obvious trauma is a diagnostic dilemma; in neurologically impaired children, the lack of sensation and repetitive trauma can lead to neuropathic injuries of the physeal plate, with bizarre X-ray changes; the problem is compounded by lack of awareness in the average orthopaedist, leading to treatment delays and unnecessary procedures like biopsy, or even surgery for osteomyelitis or malignancy, with increased morbidity and disability. We report a 12-year male child with myelomeningocele and neurological deficit; he presented with painless swelling and redness of left leg and sensory-motor deficit below the knee joints. X-rays showed distal tibial epiphysis plate widening and irregularity. A diagnosis of neuropathic epiphyseal plate injury was considered; the clinico-radiological picture only resolved after rigid immobilization in below knee POP casts and abstinence of weight bearing. Lesser changes were noted in the opposite side also. The injured physis displaced somewhat posteromedially over 8 months, but ultimately fused; contra-lateral changes subsided with partial physeal fusion. The objective of reporting this unusual case is to increase the awareness levels, and to report the bizarre radiological changes. Management involves non-weight bearing immobilization; diagnostic delays lead to more reactive changes with higher incidence of subsequent physeal closure. PMID- 20307466 TI - Elective foot and ankle surgery; activity and perioperative complications in Queensland public hospitals, Australia. AB - OBJECTIVE: To conduct an audit of elective foot and ankle surgery in Queensland public hospitals and to compare the frequency of these procedures performed to other states and territories of Australia. METHODS: ICD-10-AM data was used to extract elective foot and ankle procedures from the Data Services Unit of Queensland Health, and the Australian Institute of Health and Welfare between the years of 2000 and 2004. RESULTS: During the 4-year audit period 3846 primary procedures were performed during the 4-year period with a complication rate of 2.2% during the hospital admission period. Mean length of stay was 1.7 days. Post operative infection rates were 0.26%. With the exception of Tasmania and the Northern Territory, Queensland performs the least number of elective foot and ankle procedures per capita per year in Australia. CONCLUSIONS: This is the first reported audit of elective foot and ankle surgery for Queensland public hospitals. Complication rates cannot be directly compared to the literature as this data could only capture complications within hospital admission period. Fewer elective foot and ankle procedures were performed in Queensland public hospitals compared to all other mainland states of Australia during the data collection period. PMID- 20307467 TI - Foot orthoses and dental appliances--is there a relationship? AB - BACKGROUND: This investigation was aimed at examining whether subjects who wear a combination of functional foot orthoses and dental appliances have less postural sway and furthermore to study if these changes are direction dependent. METHODS: Centre of pressure (CoP) displacement in seven subjects, mean age 49 range (39 58) who met the inclusion criteria were evaluated using a pressure platform. Total displacement of the centre of pressure, the reduction in the displacement about the origin, area of the ellipse, total displacement along the x- and y-axes and frequency of sway along the anterior-posterior and mediolateral axes were estimated under four conditions, namely wearing orthoses and appliances, wearing only orthoses, only appliances and finally wearing neither orthoses nor appliances. RESULTS: In the six patients who had class II malocclusion there was no significant difference between the displacement (z=0.314 and p=0.753) and the frequency (z=0.680 and p=0.496) of sway along the medio-lateral or anterior posterior axes. Under control conditions the mean path length was 780 (SD 415) mm, the mean deviation from origin was 4.76 (SD 5.8) mm and the mean area was 0.83 (SD 1.87) mm(2)/cm(2). The mean deviation from origin was seen to reduce under all experimental conditions. Wearing the dental appliance alone was seen to be the most effective although the difference was not statistically significant. The sway area was also seen to reduce under all experimental conditions. The sway was most reduced when participants were wearing orthoses (i.e. conditions 1 and 3) with the reduction being the greatest when the orthoses was worn on its own (i.e. condition 3). CONCLUSION: While, foot orthoses have been used for the relief of symptoms either within or extrinsic to the foot, they could have a much wider role in the management of patients with stability problems. Results from this study highlight the need for further research in this exciting and as yet unexplored area. PMID- 20307468 TI - A new scoring system for the evaluation of clubfoot: the IMAR-Clubfoot scale. AB - BACKGROUND: Recently much interest has been shown regarding the biomechanical techniques for the assessment of clubfoot but as yet their specific role in such an endeavour is unclear. Several scoring systems have been designed but none have been adopted as a standard. The ideal system should be simple, modular, reliable, repeatable and be able to assess functional deformity objectively. OBJECTIVE: This study was aimed to develop a comprehensive scoring system and to demonstrate the potential of such an assessment tool in evaluating clubfoot. METHODS: A new innovative scoring system, the IMAR-Clubfoot scale, was designed, which incorporated clinical and biomechanical data. Clinical assessment was performed using a questionnaire and standard clinical criteria while the biomechanical evaluation was undertaken using the Podotrack, the optical dynamic pedobarograph and the GAITRite systems. Thirteen children (16 clubfeet) were recruited for assessment using the IMAR-Clubfoot scale. RESULTS: The model can detect abnormalities related to talipes equinovarus and quantify them objectively. The results also emphasise the need for such a comprehensive system, which combines clinical and biomechanical data as there was no statistical correlation between these data. CONCLUSION: The scoring system would be helpful in assessing the deformity, deciding upon appropriate management and objectively defining the success/failure of treatment at patient follow-up. PMID- 20307469 TI - Assessment of mechanical strain in the intact plantar fascia. AB - BACKGROUND: A method of measuring tri-axial plantar fascia strain that is minimally affected by external compressive force has not previously been reported. OBJECTIVE: The purpose of this study was to assess the use of micro strain gauges to examine strain in the different axes of the plantar fascia. METHOD: Two intact limbs from a thawed, fresh-frozen cadaver were dissected, and a combination of five linear and one three-way rosette gauges were attached to the fascia of the foot and ankle. Strain was assessed during two trials, both consisting of an identical controlled, loaded dorsiflexion. RESULTS: An ICC analysis of the results revealed that the majority of gauge placement sites produced reliable measures (ICC>0.75). Strain mapping of the plantar fascia indicates that the majority of the strain is centrally longitudinal, which provides supportive evidence for finite element model analysis. CONCLUSION: Although micro-strain gauges do possess the limitation of calibration difficulty, they provide a repeatable measure of fascial strain and may provide benefits in situations that require tri-axial assessment or external compression. PMID- 20307470 TI - The biomechanics and clinical efficacy of footwear adapted with rocker profiles- evidence in the literature. AB - BACKGROUND: Rocker profiles are the most commonly prescribed external therapeutic shoe modification. However, the prescription criteria for rocker profiles have historically been based on theoretical considerations with minimal scientific study and validation. OBJECTIVE: Rocker profiles are used to afford pressure relief for the plantar surface of the foot, to limit the need for sagittal plane motion in the joints of the foot and to alter gait kinetics and kinematics in proximal joints. This paper reviews the literature relating to biomechanical and clinical efficacy. METHOD: A literature search was undertaken in Medline, PubMed, Recal, Cochrane database and Scopus. RESULTS AND CONCLUSIONS: Efficacy is demonstrated with regards to relief of forefoot plantar pressures. However, the definitive profile shape has not been demonstrated. The effectiveness of rocker soled shoes in restricting sagittal plane motion in individual joints of the foot is unclear. Rocker profiles have minimal effect on the kinetics and kinematics of the more proximal joints of the lower limb, but more significant effects are seen at the ankle. Further research is warranted on the effects of rocker profiles on individual joints of the foot and the manner in which they effect lower limb muscle activity and gait patterns. PMID- 20307471 TI - A review of the differences between normal and osteoarthritis articular cartilage in human knee and ankle joints. AB - BACKGROUND: Osteoarthritis (OA) is the most common joint disease yet its pathophysiology is still poorly understood. It is more prevalent in some lower limb joints than others; in particular the knee is more commonly affected than the ankle. Research into articular cartilage and OA has primarily focussed on using animal models. However, it is apparent that articular cartilage differs between species, so more research is concentrating on human cartilage. OBJECTIVE: This paper reviews recent studies that have been undertaken to elucidate the reasons for this, and to discover if the findings would alter the conception that articular cartilage is not capable of repair. METHOD: Primary research papers into human knee and ankle cartilage published since 1997 have been reviewed. RESULTS: Differences in the structure, metabolism, physical properties and response to trauma have been found, implying that ankle cartilage may be more resistant to damage. CONCLUSIONS: More research is needed before definitive conclusions can be reached, but the findings so far suggest that OA should not be accepted as the inevitable outcome of joint injury and individuals and practitioners, such as podiatrists, may be able to use simple measures to prevent or delay its onset. PMID- 20307473 TI - Congenital subtalar dislocation--a case report. AB - Congenital dislocation of the subtalar joint is one of the rarest forms of presentation of a calcaneo-valgus foot. We report the second case of this type published; an 18-month female child aged was seen with calcaneo-valgus deformity of left foot since birth. She was walking over the medial malleolus and medial border of foot. Radiographs and 3D CT scan of the left foot confirmed the diagnosis of a congenital subtalar dislocation. Surgical correction was achieved through a posterolateral incision, and the reduced joint was fixed with a k-wires for 6 weeks; the foot was immobilized in below knee cast for another 6 weeks, and an ankle foot orthosis was used for another 3 years. At 3 years post-surgical follow up, the child has a plantigrade foot with no functional impairment. Follow up radiographs and 3D CT scan confirmed the maintenance of well aligned talo calcaneal joint. This type of dislocation should be considered in the differential diagnosis of calcaneo-valgus foot; a clear understanding of the pathology, a precise operative reduction, and long-term use of orthosis results in a favourable outcome. PMID- 20307472 TI - Management of a complex hind foot war injury with negative pressure wound therapy: a case study. AB - We report the use of Negative Pressure Wound Therapy (NPWT) in a 39 year old patient with a complex open hind foot injury. The patient sustained an open calcaneal fracture with extensive soft tissue damage following the detonation of an explosively formed penetrating round in a confined space. A remarkable recovery was made following surgical debridement, internal fixation of the fracture and use of NPWT over the soft tissue injury. The patient returned to his normal level of function, without complications within a few months. PMID- 20307474 TI - Pigmented villonodular synovitis of the talonavicular joint: a case report and review of the literature. AB - Pigmented villonodular synovitis (PVNS) is a locally aggressive synovial proliferative disorder of unknown aetiology affecting the linings of joints, tendon sheaths, and bursae. A 22-year-old female patient presented with a 3-year history of an increasingly painful swelling on the dorsum of her right foot. Examination revealed a 4 cm x 2 cm swelling that was fluctuant, tender on palpation, unattached to overlying skin and partially mobile. A firm, pedunculated intra-articular lesion from the talonavicular joint was removed at surgery. Histology revealed a nodular lesion of stromal cells and numerous giant cells with villous architecture as well as abundant haemosiderin deposition with foamy macrophages (in keeping with PVNS). The patient is currently under review by the orthopaedic oncology team. Talonavicular joint PVNS is rare. MRI scanning is the optimum investigation. Complete excision is necessary to minimise high risk of recurrence. PMID- 20307475 TI - Midfoot fusion using a locking plate system: a case report. AB - BACKGROUND: Midfoot osteoarthrosis can impede daily activity and affect lifestyle, due to pain and footwear restrictions. A case is presented of an arthrodesis of the 2nd and 3rd metatarsocuneiform joints (MCJs), undertaken using a locking plate system, to treat painful degenerative changes that had been symptomatic for 6 months. CONCLUSION: Arthrodesis of the 2nd and 3rd MCJs using a locking plate system achieved adequate fusion and the presenting complaint was resolved. The patient was delighted with the surgical outcome. PMID- 20307476 TI - The epidemiology of calcaneal fractures. AB - BACKGROUND: Calcaneal fractures are rare, but debilitating injuries, which occur frequently in younger individuals. The economic impact of the residual long-term disability that may occur after these injuries is therefore disproportionate to their incidence. The aim of this study was to review the epidemiology and injury patterns of this injury. METHODS: Data was extracted from a computer database, which prospectively coded all orthopaedic trauma events in a single unit between January 1995 and June 2005. Over this period 697 patients sustaining 752 fractures (55 bilateral) were treated in our unit. The patient's demographic details were prospectively recorded, together with details of their injury and primary treatment. The radiographs of a subgroup of patients were retrospectively examined in detail. RESULTS: The annual incidence of fracture was 11.5 per 100,000, and occurred 2.4 times more frequently in males than females. In males, the incidence was 16.5/100,000/year, with a peak incidence in the age range 20-29 (21.6/100,000/year). In females, the overall incidence was 6.26/100,000/year, with a more even spread throughout the age cohorts and showing a gradual increase in incidence towards the post-menopausal years. The majority of fractures were sustained in falls from a height (71.5%), and 64.3% of these were from 6 feet and above. Only 18.8% of fractures occurred in the workplace, and although manual workers made up the largest occupational group, significant numbers occurred in both unemployed and the retired. Most injuries occurred in isolation but the most commonly seen concomitant injuries were lower limb (13.2%) or spinal injuries (6.3%). Conventional radiography in a subgroup of the patients showed an average Bohler's angle of 16.5 degrees with no difference between the males and females. There was a strong association between the severity of the fracture, as assessed using the Sanders classification on computerised tomography, and the degree of depression of the Bohler's angle (p=0.002). PMID- 20307477 TI - Trans-metatarsal amputation in patients with a diabetic foot: reviewing 10 years experience. AB - Considerable disagreement exists whether trans-metatarsal amputations are indicated in persons with diabetes. A previous study reported that statistically the success rate of Syme's amputation in diabetic patients over 65 years of age resulted in a very poor results. The purpose of this study was to investigate the results of trans-metatarsal amputations, in patients with diabetes and to seek markers which could shed light upon the advantages/disadvantages of this procedure. The records of 46 patients covering a 10-year period (1996-2006) were used as a database. Twelve needed higher amputation level and another 10 needed a wound revision. All the patients that maintained the original amputation level walk without a need for a prosthesis and kept their previous abode. TMA in diabetic patients, although at a high risk for an extrasurgical procedure, once successful, the patient will regain his previous lifestyle. PMID- 20307478 TI - The effect on neuromuscular stability, performance, multi-joint coordination and proprioception of barefoot, taping or preventative bracing. AB - OBJECTIVE: The objective of this study was to assess the effects of taping and preventive bracing on functional balance, jumping performance, multi-joint coordination and proprioception on comparison to barefoot and each other. DESIGN: Controlled trial as an experiment with the independent variable testing in 3 trials: control (barefooted), preventive bracing, and taping. SETTING: The sports physiotherapy research laboratory. PARTICIPANTS: Twenty physically active male university students aged between 20 and 28 who had been free from lower extremity pathology for 12 months and had no previous history of ankle sprain served as participants. MAIN OUTCOME MEASURES: Single leg balance (s), jumping performance (cm), coordination and proprioception assessments by the Functional Squat System. The software automatically calculated the absolute average error (cm) and the standard deviation (SD) of the average error. Average errors were independently quantified as a function of the action mode (concentric versus eccentric) and of the lower limb (dominant versus non-dominant). RESULTS: There was no significant difference among the groups for balance tests (p>0.05). For vertical jump performance of bilateral and the dominant leg there were significant differences that the barefoot group had better results compared to the other groups (p=0.059; 0.017). According to the coordination results of Functional Squat System participants were better in brace and tape situations since the deviations were less for all concentric and eccentric positions. Deviation results for the proprioception test were different for first visual and non-visual deviations for dominant leg (p<0.05). CONCLUSION: In conclusion, bracing and taping may play an important role in preventing injury or rehabilitation of the injured ankle by improving concentric and eccentric coordination, proprioception with the ability of reproducing motion in closed kinetic chain while decreasing vertical jump performance. No superiority of brace over tape or vice versa was found in this study. PMID- 20307479 TI - A clinical guideline for the conservative management of tibialis posterior tendon dysfunction. AB - BACKGROUND: Early and appropriate conservative treatment is considered essential to prevent progression of tibialis posterior tendon dysfunction (TPTD), with its potential long term disabling consequences and the need for surgical intervention. However, there is no consensus in the literature regarding the treatment of the disorder. This investigation aimed at developing a local clinical guideline for the conservative management of TPTD by a consensus development group. METHODOLOGY: An action research methodology utilising the RAND modified Delphi approach was employed involving seven multidisciplinary consensus group participants. The guideline developed from this process was then sent for national evaluation via postal questionnaire. RESULTS: Although a difference in opinion regarding certain aspects of the conservative management of TPTD was initially present, a local consensus was achieved following extensive discussion. 86% of survey respondents from other localities found the guideline useful but their comments, which were sometimes at odds with each other, revealed a lack of national consensus regarding the management of the condition. CONCLUSION: This research project has provided empirical evidence that a local clinical guideline can be developed by a consensus group for the management of TPTD. However, the lack of national consensus regarding TPTD treatment found in this research study and as reflected in the published literature, would limit the transferability of this guideline to other localities. While, the guideline reported in this study could be used to inform the development of other national and international guidelines, different areas of expertise that emerged between professions highlighted the importance of employing a multidisciplinary group in the development of guidelines for the management of musculoskeletal conditions of the foot and ankle. PMID- 20307480 TI - Arthroscopic release of flexor hallucis longus tendon using modified posteromedial and posterolateral portals in the supine position. AB - BACKGROUND: The flexor hallucis longus (FHL) is a known site of pathological conditions. FHL stenosing tenosynovitis presents as posterior medial ankle pain or great toe discomfort and is often associated with a catching sensation of the great toe. There are a wide variety of open procedures for the treatment of FHL stenosing tenosynovitis. OBJECTIVE: Arthroscopic treatment may circumvent some of the complications associated with open surgical treatment of the hindfoot. METHODS: Arthroscopic surgery was completed in the supine position using modified posteromedial and posterolateral portals. A 70 degrees arthroscope allowed for circumferential evaluation of the ankle through the posterolateral portal including the subtalar areas and the entire FHL tendon for release using basket forceps and a 3.5mm shaver. RESULTS: This method allows for decompression of the FHL from the entrance of the fibro-osseous tunnel to the knot of Henry. Active and passive range of motion of both the ankle and toes was encouraged postoperatively. The patient returned to sporting activity 6 weeks after surgery. CONCLUSIONS: Endoscopic treatment of the FHL stenosing tenosynovitis is presented as an alternative to an open surgical procedure; it may reduce wound complications and may allow for an earlier return to sport. PMID- 20307481 TI - Treatment of gun-shot defect of the foot with bovine collagen matrix application. AB - Nonoperative therapy might be chosen for patients with small wounds or defects around the foot and ankle region. Lyophilized bovine collagen matrix is one of ideal biological dressings used in wound treatment. We present an example of type 1 bovine collagen (Gelfix, Euroresearch, Inc., Milano, Italy) usage in a complex gun-shot wound of the foot and relevant literature is discussed. PMID- 20307482 TI - Identification of a flexor digitorum accessorius longus muscle with unique distal attachments. AB - During a cadaver dissection in a gross anatomy course, a flexor digitorum accessorius longus (FDAL) muscle was identified. The FDAL was a unilateral, two headed, multipennate muscle originating from the flexor retinaculum, deep fascia, and calcaneus. The muscle bodies fused into one tendon and coursed distally where slips were observed inserting into the flexor digitorum longus tendon and the flexor hallicus longus tendon. A survey of the literature revealed that an FDAL may be present in approximately 15% of the general population. Our results concerning the FDAL suggest the need for clinicians to recognize the occurrence and variability of accessory leg and ankle muscles, and to use available technology such as MRI to assist with the diagnosis and treatment of compressive neuropathies of the foot. PMID- 20307483 TI - Interdigital pilonidal sinus of the foot. AB - Pilonidal sinus of the interdigital spaces is a common condition among barbers. The condition results from a foreign body reaction to clients' hairs. It is thought that the short sharp hairs penetrate the skin when hands are rubbed through freshly cut hair. We present an unusual case of a pilonidal sinus arising in the interdigital spaces of the foot in a female hairdresser. This is to our knowledge only the second such case reported in the literature. PMID- 20307484 TI - Complete rupture of the peroneus longus tendon secondary to injection. AB - Rupture of the peroneal tendons is rare, particularly rupture of peroneus longus. We report a case of a peroneus longus rupture following repeated steroid injection for chronic pain. PMID- 20307485 TI - Painful and tender toe, osteoid osteoma of the distal phalanx of toe, a diagnostic dilemma. AB - Osteoid osteoma rarely involves the phalanges of the toes. Basically osteoid osteoma is often a diagnostic dilemma in musculoskeletal practice especially in the foot and ankle. Its presentation is confusing and this may result in delayed diagnosis. We have reported a case of osteoid osteoma of the distal phalanx of the second toe which was treated successfully with surgical excision and reviewed the literature. PMID- 20307486 TI - An anomalous hindfoot insertion of the posterior tibialis tendon. AB - The posterior tibialis tendon has numerous insertions but none into the hindfoot has ever been reported in the literature. We present the operative and histological findings of an anomalous insertion slip into the sustentaculum tali in an adult patient with flatfoot deformity. PMID- 20307487 TI - Fast high-resolution mapping of long fragments of genomic DNA based on single molecule detection. AB - Here we describe bacterial genotyping by direct linear analysis (DLA) single molecule mapping. DLA involves preparation of restriction digest of genomic DNA labeled with a sequence-specific fluorescent probe and stained nonspecifically with intercalator. These restriction fragments are stretched one by one in a microfluidic device, and the distribution of probes on the fragments is determined by single-molecule measurement of probe fluorescence. Fluorescence of the DNA-bound intercalator provides information on the molecule length. Because the probes recognize short sequences, they encounter multiple cognate sites on 100- to 300-kb-long DNA fragments. The DLA maps are based on underlying DNA sequences of microorganisms; therefore, the maps are unique for each fragment. This allows fragments of similar lengths that cannot be resolved by standard DNA sizing techniques to be readily distinguished. DNA preparation, data collection, and analysis can be carried out in as little as 5h when working with monocultures. We demonstrate the ability to discriminate between two pathogenic Escherichia coli strains, O157:H7 Sakai and uropathogenic 536, and we use DLA mapping to identify microorganisms in mixtures. We also introduce a second color probe to double the information used to distinguish molecules and increase the length range of mapped fragments. PMID- 20307489 TI - Prevention of cardiolipin oxidation and fatty acid cycling as two antioxidant mechanisms of cationic derivatives of plastoquinone (SkQs). AB - The present state of the art in studies on the mechanisms of antioxidant activities of mitochondria-targeted cationic plastoquinone derivatives (SkQs) is reviewed. Our experiments showed that these compounds can operate as antioxidants in two quite different ways, i.e. (i) by preventing peroxidation of cardiolipin [Antonenko et al., Biochemistry (Moscow) 73 (2008) 1273-1287] and (ii) by fatty acid cycling resulting in mild uncoupling that inhibits the formation of reactive oxygen species (ROS) in mitochondrial State 4 [Severin et al. Proc. Natl. Acad. Sci. USA 107 (2009), 663-668]. The quinol and cationic moieties of SkQ are involved in cases (i) and (ii), respectively. In case (i) SkQH2 interrupts propagation of chain reactions involved in peroxidation of unsaturated fatty acid residues in cardiolipin, the formed SkQ- being reduced back to SkQH2 by heme bH of complex III in an antimycin-sensitive way. Molecular dynamics simulation showed that there are two stable conformations of SkQ1 with the quinol residue localized near peroxyl radicals at C9 or C13 of the linoleate residue in cardiolipin. In mechanism (ii), fatty acid cycling mediated by the cationic SkQ moiety is involved. It consists of (a) transmembrane movement of the fatty acid anion/SkQ cation pair and (b) back flows of free SkQ cation and protonated fatty acid. The cycling results in a protonophorous effect that was demonstrated in planar phospholipid membranes and liposomes. In mitochondria, the cycling gives rise to mild uncoupling, thereby decreasing membrane potential and ROS generation coupled to reverse electron transport in the respiratory chain. In yeast cells, dodecyltriphenylphosphonium (capital ES, Cyrillic12TPP), the cationic part of SkQ1, induces uncoupling that is mitochondria-targeted since capital ES, Cyrillic12TPP is specifically accumulated in mitochondria and increases the H+ conductance of their inner membrane. The conductance of the outer cell membrane is not affected by capital ES, Cyrillic12TPP. PMID- 20307488 TI - Blocking the K-pathway still allows rapid one-electron reduction of the binuclear center during the anaerobic reduction of the aa3-type cytochrome c oxidase from Rhodobacter sphaeroides. AB - The K-pathway is one of the two proton-input channels required for function of cytochrome c oxidase. In the Rhodobacter sphaeroides cytochrome c oxidase, the K channel starts at Glu101 in subunit II, which is at the surface of the protein exposed to the cytoplasm, and runs to Tyr288 at the heme a3/CuB active site. Mutations of conserved, polar residues within the K-channel block or inhibit steady state oxidase activity. A large body of research has demonstrated that the K-channel is required to fully reduce the heme/Cu binuclear center, prior to the reaction with O2, presumably by providing protons to stabilize the reduced metals (ferrous heme a3 and cuprous CuB). However, there are conflicting reports which raise questions about whether blocking the K-channel blocks both electrons or only one electron from reaching the heme/Cu center. In the current work, the rate and extent of the anaerobic reduction of the heme/Cu center were monitored by optical and EPR spectroscopies, comparing the wild type and mutants that block the K-channel. The new data show that when the K-channel is blocked, one electron will still readily enter the binuclear center. The one-electron reduction of the resting oxidized ("O") heme/Cu center of the K362M mutant, results in a partially reduced binuclear center in which the electron is distributed about evenly between heme a3 and CuB in the R. sphaeroides oxidase. Complete reduction of the heme/Cu center requires the uptake of two protons which must be delivered through the K-channel. PMID- 20307490 TI - Substrate binding and the catalytic reactions in cbb3-type oxidases: the lipid membrane modulates ligand binding. AB - Heme-copper oxidases (HCuOs) are the terminal components of the respiratory chain in the mitochondrial membrane or the cell membrane in many bacteria. These enzymes reduce oxygen to water and use the free energy from this reaction to maintain a proton-motive force across the membrane in which they are embedded. The heme-copper oxidases of the cbb3-type are only found in bacteria, often pathogenic ones since they have a low Km for O2, enabling the bacteria to colonize semi-anoxic environments. Cbb3-type (C) oxidases are highly divergent from the mitochondrial-like aa3-type (A) oxidases, and within the heme-copper oxidase family, cbb3 is the closest relative to the most divergent member, the bacterial nitric oxide reductase (NOR). Nitric oxide reductases reduce NO to N2O without coupling the reaction to the generation of any electrochemical proton gradient. The significant structural differences between A- and C-type heme copper oxidases are manifested in the lack in cbb3 of most of the amino acids found to be important for proton pumping in the A-type, as well as in the different binding characteristics of ligands such as CO, O2 and NO. Investigations of the reasons for these differences at a molecular level have provided insights into the mechanism of O2 and NO reduction as well as the proton pumping mechanism in all heme-copper oxidases. In this paper, we discuss results from these studies with the focus on the relationship between proton transfer and ligand binding and reduction. In addition, we present new data, which show that CO binding to one of the c-type hemes of CcoP is modulated by protein-lipid interactions in the membrane. These results show that the heme c-CO binding can be used as a probe of protein-membrane interactions in cbb3 oxidases, and possible physiological consequences for this behavior are discussed. PMID- 20307491 TI - Cocaine produces D2R-mediated conformational changes in the adenosine A(2A)R dopamine D2R heteromer. AB - Adenosine A(2A) receptors (A(2A)Rs) and dopamine D(2) receptors (D(2)Rs) form constitutive heteromers in living cells and exhibit a strong functional antagonistic interaction. Recent findings give neurochemical evidence that extended cocaine self-administration in the rat give rise to an up-regulation of functional A(2A)Rs in the nucleus accumbens that return to baseline expression levels during cocaine withdrawal. In the present work, the acute in vitro effects of a concentration of cocaine known to fully block the dopamine (DA) transporter without exerting any toxic actions were investigated on A(2A)R and D(2L)R formed heteromers in transiently co-transfected HEK-293T cells. In vitro treatment of cocaine was found to produce changes in D(2)R homodimers and in A(2A)R-D(2)R heterodimers detected through bioluminescent energy transfer (BRET). Cocaine was found to produce a time- and concentration-dependent reduction in the BRET(max) between A(2A)R-D(2L)R heterodimers and D(2L)R homodimers, but not A(2A)R homodimers, indicating its effect on D(2)R. Cocaine was evaluated with regard to D(2)R binding using a human D(2L)R stable expressing CHO cell line and was found to produce an increase in the affinity of hD(2L)R for DA. At the level of G protein-coupling, cocaine produced a small, but significant increase in DA stimulated binding of GTPgammaS. However, cocaine failed to modulate D(2)R agonist-induced inhibition of cAMP in stable hD(2L)R CHO cells or the gating of GIRK channels in oocytes. Taken together, these results indicate a direct and specific effect of a moderate concentration of cocaine on the DA D(2L)R, that results in enhanced agonist recognition, G protein-coupling and an altered conformational state of D(2)R homodimers and A(2A)R-D(2)R heterodimers. PMID- 20307492 TI - Ethyl pyruvate has a neuroprotective effect through activation of extracellular signal-regulated kinase in Parkinson's disease model. AB - Ethyl pyruvate (EP), a simple derivative of endogenous pyruvate, has an anti inflammatory function. Recently, the protective neurological effects of EP have been reported in cell culture and animal models of neurological diseases. The present study investigates the protective effects of EP on dopaminergic cell death in Parkinson's disease models. The selective death of dopaminergic neurons in substantia nigra was prevented by EP in 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine mouse models. EP also suppressed the 1-methyl-4-pyridinium induced cell death of SH-SY5Y cells and restored the phosphorylation of extracellular signal-regulated kinase. Thus, EP has neuroprotective effects of EP in Parkinson's disease and its related signaling pathways. PMID- 20307493 TI - Vitamin E as a novel enhancer of macroautophagy in rat hepatocytes and H4-II-E cells. AB - Autophagy is an intracellular bulk degradation process induced by nutrient starvation, and contributes to macromolecular turnover and rejuvenation of cellular organelles. We demonstrated that vitamin E was a novel nutritional enhancer of autophagy in freshly isolated rat hepatocytes and rat hepatoma H4-II E cells. Supplementation of fresh hepatocytes with vitamin E (up to 100 microM) increased proteolysis significantly in the presence or absence of amino acids in a dose-dependent manner. The cytosolic LC3 ratio, a newly established index of autophagic flux, was significantly increased by vitamin E, strongly suggesting that the possible site of action is the LC3 conversion step, an early step in autophagosome formation. A typical antioxidant, alpha-lipoic acid, exerted autophagy suppression, while H(2)O(2) stimulated autophagy. It is conceivable that autophagy was stimulated by oxidative stress and this stimulation was cancelled by cellular antioxidative effects. However, in our studies, vitamin E could have enhanced autophagy over-stimulation by H(2)O(2), rather than suppress it. From these results, using a new cytosolic LC3 ratio, vitamin E increases autophagy by accelerating LC3 conversion through a new signaling pathway, emerging as a novel enhancer of autophagy. PMID- 20307494 TI - Inhibition of mitochondrial division through covalent modification of Drp1 protein by 15 deoxy-Delta(12,14)-prostaglandin J2. AB - Arachidonic acid derived endogenous electrophile 15d-PGJ2 has gained much attention in recent years due to its potent anti-proliferative and anti inflammatory actions mediated through thiol modification of cysteine residues in its target proteins. Here, we show that 15d-PGJ2 at 1 microM concentration converts normal mitochondria into large elongated and interconnected mitochondria through direct binding to mitochondrial fission protein Drp1 and partial inhibition of its GTPase activity. Mitochondrial elongation induced by 15d-PGJ2 is accompanied by increased assembly of Drp1 into large oligomeric complexes through plausible intermolecular interactions. The role of decreased GTPase activity of Drp1 in the formation of large oligomeric complexes is evident when Drp1 is incubated with a non-cleavable GTP analog, GTPgammaS or by a mutation that inactivated GTPase activity of Drp1 (K38A). The mutation of cysteine residue (Cys644) in the GTPase effector domain, a reported target for modification by reactive electrophiles, to alanine mimicked K38A mutation induced Drp1 oligomerization and mitochondrial elongation, suggesting the importance of cysteine in GED to regulate the GTPase activity and mitochondrial morphology. Interestingly, treatment of K38A and C644A mutants with 15d-PGJ2 resulted in super oligomerization of both mutant Drp1s indicating that 15d-PGJ2 may further stabilize Drp1 oligomers formed by loss of GTPase activity through covalent modification of middle domain cysteine residues. The present study documents for the first time the regulation of a mitochondrial fission activity by a prostaglandin, which will provide clues for understanding the pathological and physiological consequences of accumulation of reactive electrophiles during oxidative stress, inflammation and degeneration. PMID- 20307495 TI - Hypoxia-induced Bcl-2 expression in endothelial cells via p38 MAPK pathway. AB - Angiogenesis and apoptosis are reciprocal processes in endothelial cells. Bcl-2, an anti-apoptotic protein, has been found to have angiogenic activities. The purpose of this study was to determine the role of Bcl-2 in hypoxia-induced angiogenesis in endothelial cells and to investigate the underlying mechanisms. Human aortic endothelial cells (HAECs) were exposed to hypoxia followed by reoxygenation. Myocardial ischemia and reperfusion mouse model was used and Bcl-2 expression was assessed. Bcl-2 expression increased in a time-dependent manner in response to hypoxia from 2 to 72h. Peak expression occurred at 12h (3- to 4-fold, p<0.05). p38 inhibitor (SB203580) blocked hypoxia-induced Bcl-2 expression, whereas PKC, ERK1/2 and PI3K inhibitors did not. Knockdown of Bcl-2 resulted in decreased HAECs' proliferation and migration. Over-expression of Bcl-2 increased HAECs' tubule formation, whereas knockdown of Bcl-2 inhibited this process. In this model of myocardial ischemia and reperfusion, Bcl-2 expression was increased and was associated with increased p38 MAPK activation. Our results showed that hypoxia induces Bcl-2 expression in HAECs via p38 MAPK pathway. PMID- 20307496 TI - The creation of the artificial RING finger from the cross-brace zinc finger by alpha-helical region substitution. AB - The creation of the artificial RING finger as ubiquitin-ligating enzyme (E3) has been demonstrated. In this study, by the alpha-helical region substitution between the EL5 RING finger and the Williams-Beuren syndrome transcription factor (WSTF) PHD finger, the artificial E3 (WSTF PHD_RING finger) was newly created. The experiments of the chemical modification of residues Cys and the circular dichroism spectra revealed that the WSTF PHD_RING finger binds two zinc atoms and adopts the zinc-dependent ordered-structure. In the substrate-independent ubiquitination assay, the WSTF PHD_RING finger functions as E3 and was poly- or mono-ubiquitinated. The present strategy is very simple and convenient, and consequently it might be widely applicable to the creation of various artificial E3 RING fingers with the specific ubiquitin-conjugating enzyme (E2)-binding capability. PMID- 20307497 TI - Homeodomain-interacting protein kinase 2 (HIPK2) targets beta-catenin for phosphorylation and proteasomal degradation. AB - The regulation of intracellular beta-catenin levels is central in the Wnt/beta catenin signaling cascade and the activation of the Wnt target genes. Here, we show that homeodomain-interacting protein kinase 2 (HIPK2) acts as a negative regulator of the Wnt/beta-catenin pathway. Knock-down of endogenous HIPK2 increases the stability of beta-catenin and results in the accumulation of beta catenin in the nucleus, consequently enhancing the expression of Wnt target genes and cell proliferation both in vivo and in cultured cells. HIPK2 inhibits TCF/LEF mediated target gene activation via degradation of beta-catenin. HIPK2 phosphorylates beta-catenin at its Ser33 and Ser37 residues without the aid of a priming kinase. Substitutions of Ser33 and Ser37 for alanines abolished the degradation of beta-catenin associated with HIPK2. In ex vivo mouse model, HIPK2 knock-down resulted in accumulation of beta-catenin, thereby potentiated beta catenin-mediated cell proliferation and tumor formation. Furthermore, the axis duplication induced by the ectopic expression of beta-catenin was blocked by co injection of HIPK2 mRNAs into Xenopus embryos. Taken together, HIPK2 appears to function as a novel negative regulator of beta-catenin through its phosphorylation and proteasomal degradation. PMID- 20307498 TI - The tip region of the MacA alpha-hairpin is important for the binding to TolC to the Escherichia coli MacAB-TolC pump. AB - The tripartite efflux pump MacAB-TolC found in gram-negative bacteria is involved in resistance to antibiotics. We previously reported the funnel-like hexameric structure of the adaptor protein MacA to be physiologically relevant. In this study, we investigated the role of the tip region of its alpha-hairpin, which forms a cogwheel structure in the funnel-like shape of the MacA hexamer. Mutational and biochemical analyses revealed that the conserved residues located at the tip region of the alpha-hairpin of MacA play an essential role in the binding of TolC. Our findings offer a molecular basis for understanding the drug resistance of pathogenic bacteria. PMID- 20307499 TI - Calcium-sensing receptor activation contributed to apoptosis stimulates TRPC6 channel in rat neonatal ventricular myocytes. AB - Capacitative calcium entry (CCE) refers to the influx of calcium through plasma membrane channels activated on depletion of endoplasmic sarcoplasmic/reticulum (ER/SR) Ca(2+) stores, which is performed mainly by the transient receptor potential (TRP) channels. TRP channels are expressed in cardiomyocytes. Calcium sensing receptor (CaR) is also expressed in rat cardiac tissue and plays an important role in mediating cardiomyocyte apoptosis. However, there are no data regarding the link between CaR and TRP channels in rat heart. In this study, in rat neonatal myocytes, by Ca(2+) imaging, we found that the depletion of ER/SR Ca(2+) stores by thapsigargin (TG) elicited a transient rise in cytoplasmic Ca(2+) ([Ca(2+)](i)), followed by sustained increase depending on extracellular Ca(2+). But, TRP channels inhibitor (SKF96365), not L-type channels or the Na(+)/Ca(2+) exchanger inhibitors, inhibited [Ca(2+)](i) relatively high. Then, we found that the stimulation of CaR with its activator gadolinium chloride (GdCl(3)) or by an increased extracellular Ca(2+)([Ca(2+)](o)) increased the concentration of intracelluar Ca(2+), whereas, the sustained elevation of [Ca(2+)](i) was reduced in the presence of SKF96365. Similarly, the duration of [Ca(2+)](i) increase was also shortened in the absence of extracellular Ca(2+). Western blot analysis showed that GdCl(3) increased the expression of TRPC6, which was reversed by SKF96365. Additionally, SKF96365 reduced cardiomyocyte apoptosis induced by GdCl(3). Our results suggested that CCE exhibited in rat neonatal myocytes and CaR activation induced Ca(2+)-permeable cationic channels TRPCs to gate the CCE, for which TRPC6 was one of the most likely candidates. TRPC6 channel was functionally coupled with CaR to enhance the cardiomyocyte apoptosis. PMID- 20307500 TI - Conserved CA-rich motifs in gene promoters of Pt x tMYB021-responsive secondary cell wall carbohydrate-active enzymes in Populus. AB - In order to understand gene regulation during wood formation, we cloned a MYB46 like gene in hybrid aspen, Populus tremula x tremuloides, called Pt x tMYB021. Phylogenetic and paired identity analysis of MYB46-like genes in Populus and Arabidopsis reveals relationships between paralogous pairs of Populus MYB46-like proteins and their Arabidopsis counterparts MYB46 and MYB83, and suggest that Pt x tMYB021 is the ortholog of MYB46. Pt x tMYB021 is expressed mainly in xylem tissues, and transiently expressed Pt x tMYB46 transactivates gene promoters of xylan-active CAZymes GT43A, GT43B and Xyn10A. Analysis of conserved motifs within these promoters identify the sequence CCACCAAC, called ACTYP, which is similar to the AC elements mediating transactivation by MYB transcription factors during lignin biosynthesis. Further analysis by Motif Finder identifies four 6 bp CA rich motifs overlapping ACTYP, and we show that these motifs are enriched in xylem-specific promoters. We propose that AC-type regulatory elements mediate xylem-specific MYB46-dependent expression of secondary cell wall carbohydrate active enzymes (CAZymes), besides activating gene expression of lignin biosynthesis enzymes. PMID- 20307501 TI - Connexin 26 (GJB2) mutations as a cause of the KID syndrome with hearing loss. AB - KID syndrome (MIM 148210) is an ectodermal dysplasia characterized by the occurrence of localized erythematous scaly skin lesions, keratitis and severe bilateral sensorineural deafness. KID syndrome is inherited as an autosomic dominant disease, due to mutations in the gene encoding gap junction protein GJB2 (connexin 26, Cx26). Cx26 is a component of gap junction channels in the epidermis and in the stria vascularis of the cochlea. These channels play a role in the coordinated exchange of molecules and ions occurring in a wide spectrum of cellular activities. In this paper we describe two patients with Cx26 mutations cause cell death by the alteration of protein trafficking, membrane localization and probably interfering with intracellular ion concentrations. We discuss the pathogenesis of both the hearing and skin phenotypes. PMID- 20307502 TI - Deep sequencing of coding and non-coding RNA in the CNS. AB - Several methods now exist for identifying and quantifying many biological events in parallel and in a relatively unbiased fashion. For gene expression experiments, cloning approaches have been supplemented with microarray platforms over the past few years. The focus of this review is on deep sequencing, a new set of techniques that can be used to both identify RNA species and quantify them in a massively parallel fashion. Deep sequencing has some advantages over other methods, driven largely by the high depth of coverage for any library of nucleic acids. This allows, for example, estimates of alternative splicing and untranslated region utilization. We will discuss how deep sequencing methods are being applied to characterization of gene expression in the brain and how these technologies might develop over the next few years. PMID- 20307504 TI - Oxidative stress activates STAT1 in basilar arteries after subarachnoid hemorrhage. AB - The signal transducer and activator of transcription 1 (STAT1) is one of the most important signaling molecule transducing signals from the cell surface in response to cytokines or growth factors. Subarachnoid hemorrhage (SAH) results in production of cytokines and growth factors in the CSF. We here investigated whether this signaling molecule is activated in the rat basilar artery after SAH. In a rat single-hemorrhage model of SAH, basilar arteries were obtained at various times until 7days after SAH. Western blot analysis with phosphorylated (p)-STAT1 at Tyr(701), p-STAT1 at Ser(727), STAT1, and actin antibodies was performed. The expression of STAT1 and p-STAT1 at Tyr(701) in basilar arteries was also examined by immunohistochemistry. Intracisternal injection of interleukin-6 (IL-6), hydrogen peroxide, or hydroxyl radical scavenger was conducted to examine for phosphorylation of STAT1. Western blot analysis showed STAT1 to be significantly phosphorylated at Tyr(701) and Ser(727) within 2h of SAH and to gradually decrease thereafter. Immunohistochemistry revealed this phosphorylation of STAT1 to occur in the outer membranes of the basilar artery. Intracisternal injection of hydrogen peroxide, but not IL-6, also significantly increased phosphorylation of STAT1 at Tyr(701). Hydroxyl radical scavenger significantly reduced phosphorylation of STAT1. These results indicate that reactive oxygen species, produced in the CSF after SAH, activates STAT1 molecule in the outer membranes of basilar arteries. This STAT1 signaling might contribute to morphological arterial wall changes in cerebral vasospasm. PMID- 20307505 TI - Neural correlates of forgiveness for moral transgressions involving deception. AB - We used positron emission tomography (PET) to investigate the neural mechanisms underlying the willingness to forgive another person's moral transgression involving deception. During scanning, 12 subjects were asked to judge the forgivability of a perpetrator's moral transgression. These transgressions were described by four kinds of scenarios composed of a combination of two factors: the attitude of the perpetrator (dishonest or honest) and the severity of the moral transgression (serious or minor). Behavioral data showed that both the perpetrator's dishonesty and the seriousness of the scenario decreased the subjects' willingness to forgive the moral transgression. Neuroimaging data revealed that, relative to honest responses, a perpetrator's dishonest responses were associated with right ventromedial prefrontal activity, which possibly reflects the subjects' identification of the perpetrator's deception. The opposite comparison did not show significant activation. Moreover, a comparison of serious scenarios with minor scenarios did not reveal significant activation. Instead, minor scenarios, relative to serious scenarios, evoked activity in the right middle frontal gyrus and the right caudate nucleus, possibly reflecting increased demand on frontal control system function. Further analysis revealed that the left ventromedial prefrontal cortex showed a significant interaction between the two factors, indicating that this region functions as a mediator of the two factors, modulating judgments regarding the forgivability of moral transgressions. Taken together, these findings suggest that the ventromedial prefrontal cortex plays a key role in the forgiveness of moral transgressions involving deception. PMID- 20307503 TI - Regulatory RNAs in brain function and disorders. AB - Regulatory RNAs are being increasingly investigated in neurons, and important roles in brain function have been revealed. Regulatory RNAs are non-protein coding RNAs (npcRNAs) that comprise a heterogeneous group of molecules, varying in size and mechanism of action. Regulatory RNAs often exert post-transcriptional control of gene expression, resulting in gene silencing or gene expression stimulation. Here, we review evidence that regulatory RNAs are implicated in neuronal development, differentiation, and plasticity. We will also discuss npcRNA dysregulation that may be involved in pathological states of the brain such as neurodevelopmental disorders, neurodegeneration, and epilepsy. PMID- 20307506 TI - Effects of protostane-type triterpenoids on the 5-HT3A receptor-mediated ion current in Xenopus oocytes. AB - Alisol derivatives are unique protostane-type triterpenoid compounds that are isolated from Alismatis rhizoma, which is a well-known traditional medicine in East Asia. In the present study, we investigated the effects of protostane-type triterpenoids (AA, Alisol A; AB, Alisol B; AB-ac, Alisol B 23-acetate; AC-ac, Alisol C 23-aceteate) on 5-HT-induced currents mediated by the human 5-HT(3)A receptor expressed in Xenopus laevis oocytes. Co-treatment with triterpenoids regulated the 5-HT-induced inward peak current in a concentration-dependent and reversible manner. In addition, regulation of I(5-HT) by triterpenoids occurred in a non-competitive manner. Taken together, these results indicate that triterpenoids may regulate the 5-HT(3)A receptors that are expressed in Xenopus oocytes. Furthermore, this regulation of the ligand-gated ion channel activity by triterpenoids may be one of the pharmacological actions of Alismatis rhizoma. PMID- 20307507 TI - Who is ziji? ERP responses to the Chinese reflexive pronoun during sentence comprehension. AB - The Principle A of Chomsky's (1981) Binding Theory requires the reflexive pronoun in a sentence to be bound to its antecedent within its governing category. However, in Chinese sentences with a common structure "P-NP(1)+VP(1)+P NP(2)+VP(2)+ziji", in which the P-NP stands for personal name and the reflexive ziji (standing for myself, himself, herself, yourself, ourselves etc., depending on context) is at the object position, ziji can refer to either the local subject (P-NP(2), local reference) or the matrix or main subject (P-NP(1), long-distance reference) or both (ambiguous reference), depending on properties of VP(2). This study investigates whether this violation of Principle A comes with processing costs during sentence comprehension. In an event-related potential (ERP) experiment we found that, as compared with the local reference condition, ERP responses to ziji were significantly more positive in the long-distance reference condition. This pattern appeared on both P300 and P600. It is suggested that linking the reflexive with a distant, rather than a local, antecedent during sentence comprehension requires more processing resources. While the P300 effect may reflect the detection of incongruence between the mental representation based on Principle A and the representation based on the processing of local verb, the P600 effect may be associated with a second-pass integration process that links the reflexive with the matrix subject. PMID- 20307508 TI - A temporal constraint for automatic deviance detection and object formation: A mismatch negativity study. AB - The automatic detection of deviations within a constant sine wave tone is confined to the initial part of approximately 350 ms. When a deviation occurs beyond this critical limit, the mismatch negativity (MMN) - a deviance-related component of the event-related potential - is largely attenuated or even absent. However, for time-variant acoustic stimuli such as speech sounds or tonal patterns, MMN is also obtained for deviations beyond the initial 350 ms. We consider two hypotheses that can explain the MMN to time-variant sounds. One is that the terminal part of those sounds is represented as the spectral information varies over time (spectral-variation hypothesis). The other is that transients, occurring in time-variant signals, help to segment the long sounds into smaller units, each being not larger than the critical 350 ms (segmentation hypothesis). We measured MMN to duration shortenings (deviants) embedded in a sequence of 1000 ms long standard tones of increasing frequency (sweeps). The sweeps did or did not contain a noise burst. Results reveal a lack of MMN to the duration deviant in the sweep without a noise burst, which rules out the spectral-variation hypothesis. The presence of MMN to the duration deviant in the sweep with a noise burst supports the segmentation hypothesis. Thus, the results suggest a temporal constraint inherent to the processing of unstructured/unsegmented long tones. We argue that transients within a sound act as segmentation cues providing an automatic sound representation for which deviations can be detected. PMID- 20307510 TI - Specificity of glucocorticoid receptor primary antibodies for analysis of receptor localization patterns in cultured cells and rat hippocampus. AB - After glucocorticoid stimulation, glucocorticoid receptors (GRs) are translocated to the nucleus to modulate transcription of glucocorticoid target genes. The subcellular distribution and trafficking of GR in cultured cells has been studied quite intensively using several techniques. However, the intracellular localization of nuclear receptors in ligand-free and stimulated conditions in vivo is still controversial, in part because of inconsistent results with different antibodies. Knowledge of trafficking of GR in vivo could greatly contribute to understanding nuclear receptor signaling. Therefore, in this study we systematically compared a panel of different primary GR antibodies using immunohistochemistry and confocal imaging. Nuclear translocation patterns at different time points after glucocorticoid stimulation were compared in cultured AtT20 cells and rat hippocampal CA1 and dentate gyrus cells. The BuGR2 antibody consistently detected GR nuclear translocation patterns between in vivo and in vitro settings, but the other GR primary antibodies provided contradictory results. While GR H300 and P20 strongly detected nuclear GR immunoreactivity after glucocorticoid stimulation in both CA1 and dentate gyrus cells, the same antibodies provided poor results in cultured cells. The opposite was found for the primary GR M20 antibody. These data indicate that with a particular glucocorticoid receptor antibody the findings in cell culture studies cannot always be extrapolated to in vivo situations. Moreover, different antibodies disclose different features of the glucocorticoid receptor translocation process. PMID- 20307509 TI - A helper virus-free HSV-1 vector containing the vesicular glutamate transporter-1 promoter supports expression preferentially in VGLUT1-containing glutamatergic neurons. AB - Multiple potential uses of direct gene transfer into neurons require restricting expression to specific classes of glutamatergic neurons. Thus, it is desirable to develop vectors containing glutamatergic class-specific promoters. The three vesicular glutamate transporters (VGLUTs) are expressed in distinct populations of neurons, and VGLUT1 is the predominant VGLUT in the neocortex, hippocampus, and cerebellar cortex. We previously reported a plasmid (amplicon) Herpes Simplex Virus (HSV-1) vector that placed the Lac Z gene under the regulation of the VGLUT1 promoter (pVGLUT1lac). Using helper virus-free vector stocks, we showed that this vector supported approximately 90% glutamatergic neuron-specific expression in postrhinal (POR) cortex, in rats sacrificed at either 4 days or 2 months after gene transfer. We now show that pVGLUT1lac supports expression preferentially in VGLUT1-containing glutamatergic neurons. pVGLUT1lac vector stock was injected into either POR cortex, which contains primarily VGLUT1 containing glutamatergic neurons, or into the ventral medial hypothalamus (VMH), which contains predominantly VGLUT2-containing glutamatergic neurons. Rats were sacrificed at 4 days after gene transfer, and the types of cells expressing ss galactosidase were determined by immunofluorescent costaining. Cell counts showed that pVGLUT1lac supported expression in approximately 10-fold more cells in POR cortex than in the VMH, whereas a control vector supported expression in similar numbers of cells in these two areas. Further, in POR cortex, pVGLUT1lac supported expression predominately in VGLUT1-containing neurons, and, in the VMH, pVGLUT1lac showed an approximately 10-fold preference for the rare VGLUT1 containing neurons. VGLUT1-specific expression may benefit specific experiments on learning or specific gene therapy approaches, particularly in the neocortex. PMID- 20307511 TI - RNAi therapeutics for CNS disorders. AB - RNA interference (RNAi) is a process of sequence-specific gene silencing and serves as a powerful molecular tool to manipulate gene expression in vitro and in vivo. RNAi technologies have been applied to study gene function and validate drug targets. Researchers are investigating RNAi-based compounds as novel therapeutics to treat a variety of human diseases that are currently lacking sufficient treatment. To date, numerous studies support that RNAi therapeutics can improve disease phenotypes in various rodent models of human disease. Here, we focus on the development of RNAi-based therapies aimed at treating neurological disorders for which reduction of mutant or toxic gene expression may provide clinical benefit. We review RNAi-based gene-silencing strategies, proof of-concept studies testing therapeutic RNAi for CNS disorders, and highlight the most recent research aimed at transitioning RNAi-based therapeutics toward clinical trials. PMID- 20307512 TI - Synchronous retinotopic frontal-temporal activity during long-term memory for spatial location. AB - Early visual areas in occipital cortex are known to be retinotopic. Recently, retinotopic maps have been reported in frontal and parietal cortex during spatial attention and working memory. The present event-related potential (ERP) and functional magnetic resonance imaging (fMRI) study determined whether spatial long-term memory was associated with retinotopic activity in frontal and parietal regions, and assessed whether retinotopic activity in these higher level control regions was synchronous with retinotopic activity in lower level visual sensory regions. During encoding, abstract shapes were presented to the left or right of fixation. During retrieval, old and new shapes were presented at fixation and participants classified each shape as old and previously on the "left", old and previously on the "right", or "new". Retinotopic effects were manifested by accurate memory for items previously presented on the left producing activity in the right hemisphere and accurate memory for items previously presented on the right producing activity in the left hemisphere. Retinotopic ERP activity was observed in frontal regions and visual sensory (occipital and temporal) regions. In frontal cortex, retinotopic fMRI activity was localized to the frontal eye fields. There were no significant ERP or fMRI retinotopic memory effects in parietal regions. The present long-term memory retinotopic effects complement previous spatial attention and working memory findings (and suggest retinotopic activity in parietal cortex may require an external peripheral stimulus). Furthermore, ERP cross-correlogram analysis revealed that retinotopic activations in frontal and temporal regions were synchronous, indicating that these regions interact during retrieval of spatial information. PMID- 20307513 TI - Bone marrow stromal cell transplantation for treatment of sub-acute spinal cord injury in the rat. AB - Bone marrow stromal cells (BMSCs) have been studied as effective transplants for the treatment of spinal cord injury (SCI). Our previous study showed that BMSCs infused into the cerebrospinal fluid (CSF) exhibited distinct effects on the recovery of acute SCI. The present study examined the effects of BMSCs in sub acute SCI (2weeks post-injury) by transplanting them directly into the lesion. The spinal cord was crush-injured at the Th8-9 level in rats, and 2weeks later, cultured BMSCs (5x10(5)) derived from GFP-transgenic rats of the same strain were transplanted into the lesion. Tissue repair and nerve regeneration were examined by immunohistochemistry and electron microscopy. GFP-labeled BMSCs survived as cell assemblies in the spinal cord for 1-2weeks after transplantation. The dorsal side of BMSC assemblies in the spinal cord usually showed an expanded GFAP negative, astrocyte-devoid area, in which extracellular matrices including collagen fibrils were deposited. Numerous regenerating axons associated with Schwann cells grew out through such astrocyte-devoid extracellular matrices. Ascending (CGRP-containing) and descending (5HT- and TH-containing) axons were included in these regenerating axons. Regenerated axons were myelinated by Schwann cells beyond 2weeks post-transplantation. Cavity formation was reduced in the cell transplantation group. Locomotory behavior assessed by the BBB scale improved to 9.8 points in the cell transplantation group, while it was to 5.5-5.7 in the control. BMSC transplantation into lesions of advanced SCI has markedly beneficial effects on tissue repair and axonal outgrowth, leading to improved locomotion in rats. PMID- 20307514 TI - Metabolism of carbosulfan II. Human interindividual variability in its in vitro hepatic biotransformation and the identification of the cytochrome P450 isoforms involved. AB - This study aims to characterize interindividual variability and individual CYP enzymes involved in the in vitro metabolism of the carbamate insecticide carbosulfan. Microsomes from ten human livers (HLM) were used to characterize the interindividual variability in carbosulfan activation. Altogether eight phase I metabolites were analyzed by LC-MS. The primary metabolic pathways were detoxification by the initial oxidation of sulfur to carbosulfan sulfinamide ('sulfur oxidation pathway') and activation via cleavage of the nitrogen sulfur bond (N-S) to give carbofuran and dibutylamine ('carbofuran pathway'). Differences between maximum and minimum carbosulfan activation values with HLM indicated nearly 5.9-, 7.0, and 6.6-fold variability in the k(m), V(max) and CL(int) values, respectively. CYP3A5 and CYP2B6 had the greatest efficiency to form carbosulfan sulfinamide, while CYP3A4 and CYP3A5 were the most efficient in the generation of the carbofuran metabolic pathway. Based on average abundances of CYP enzymes in human liver, CYP3A4 contributed to 98% of carbosulfan activation, while CYP3A4 and CYP2B6 contributed 57 and 37% to detoxification, respectively. Significant correlations between carbosulfan activation and CYP marker activities were seen with CYP3A4 (omeprazole sulfoxidation), CYP2C19 (omeprazole 5-hydroxylation) and CYP3A4 (midazolam 1'-hydroxylation), displaying r(2)=0.96, 0.87 and 0.82, respectively. Activation and detoxification pathways were inhibited by ketoconazole, a specific CYP3A4 inhibitor, by 90-97% and 47 94%, respectively. Carbosulfan inhibited relatively potently CYP3A4 and moderately CYP1A1/2 and CYP2C19 in pooled HLM. These results suggest that the carbosulfan activation pathway is more important than the detoxification pathway, and that carbosulfan activation is predominantly catalyzed in humans by CYP3A4. PMID- 20307515 TI - Modulation of PPAR-gamma by telmisartan protects the heart against myocardial infarction in experimental diabetes. AB - Telmisartan, an angiotensin II-receptor blocker (ARB), is a partial agonist of the peroxisome proliferator-activated receptor-gamma (PPAR-gamma). We investigated whether telmisartan improved the pathophysiology of myocardial infarction in diabetes partially through the PPAR-gamma pathway by assessing a variety of indices, e.g., hemodynamic, biochemical, histoarchitectural changes, and apoptosis. Diabetes was induced by a single dose of streptozotocin (70 mg/kg, IP). Diabetic rats received either telmisartan (10 mg/kg/day, orally), the PPAR gamma antagonist GW9662 (1 mg/kg/day, IP), or both for 14 days with concurrent administration of isoproterenol (85 mg/kg, SC) on days 13 and 14. Compared with diabetic controls, diabetic rats with myocardial infarction exhibited altered hemodynamic profiles and reduction in the activities of creatine kinase-MB isoenzyme, lactate dehydrogenase, superoxide dismutase, catalase, and glutathione level along with increased level of malondialdehyde in the heart. Further, diabetic animals with myocardial infarction exhibited increased myonecrosis, edema, and apoptotic cell death. Treatment with telmisartan significantly improved the redox status of the myocardium with subsequent cardiac functional recovery. However, significant effects were lowered in animals treated with telmisartan plus GW9662. Telmisartan markedly inhibited Bax expression, TUNEL positive cells, myonecrosis, and edema. On the other hand, administration of telmisartan plus GW9662 did not elicit the same effects, nor did they increase Bcl-2 protein expression in isoproterenol-induced myocardially infarcted diabetic rats when administered concomitantly or individually. Moreover, down-regulated PPAR-gamma expression in myocardially infarcted diabetic hearts was increased by telmisartan treatment. In addition to class effects of ARBs, telmisartan reduces oxidative stress and apoptosis and improves cardiac function via the PPAR-gamma pathway. PMID- 20307516 TI - Resveratrol attenuates hyperglycemia-mediated oxidative stress, proinflammatory cytokines and protects hepatocytes ultrastructure in streptozotocin-nicotinamide induced experimental diabetic rats. AB - The present study was hypothesized to investigate the hepatoprotective nature of resveratrol in averting hyperglycemia-mediated oxidative stress by measuring extent of oxidant stress and levels of proinflammatory cytokines and antioxidant competence in the hepatic tissues of streptozotocin-nicotinamide-induced diabetic rats. After the experimental period of 30 days, the pathophysiological markers such as serum bilirubin and hepatic aspartate transaminase (AST), alanine transaminase (ALT) and alkaline phosphatase (ALP) were studied in addition to hepatic TNF-alpha, IL-1 beta, IL-6, NF-kappaB p65 and nitric oxide (NO) levels in control and experimental groups of rats. The levels of vitamin C, vitamin E and reduced glutathione (GSH) and activities of superoxide dismutase (SOD), catalase, glutathione peroxidase (GPx), glutathione-S-transferase (GST) and glutathione reductase (GR) were determined in the liver tissues. Extent of oxidative stress was also assessed by hepatic lipid peroxides, hydroperoxides and protein carbonyls. A portion of liver was processed for histological and ultrastructural studies. Oral administration of resveratrol (5mg/kg b.w.) to diabetic rats showed a significant decline in hepatic proinflammatory cytokines and notable attenuation in hepatic lipid peroxides, hydroperoxides and protein carbonyls. The diminished activities of hepatic enzymic antioxidants as well as the decreased levels of hepatic non-enzymic antioxidants of diabetic rats were reverted to near normalcy by resveratrol administration. Moreover, the histological and ultrastructural observations evidenced that resveratrol effectively rescues the hepatocytes from hyperglycemia-mediated oxidative damage without affecting its cellular function and structural integrity. The findings of the present investigation demonstrated the hepatocyte protective nature of resveratrol by attenuating markers of hyperglycemia-mediated oxidative stress and antioxidant competence in hepatic tissues of diabetic rats. PMID- 20307517 TI - Current treatment options for people with Alzheimer's disease in Croatia. AB - About 16% of the population in Croatia is older than 65 years. Croatia has no register of persons with dementia (PWD), but based on a calculation that 10% of persons over 65 years are affected by dementia, the approximate number of PWD would be 80,000, the majority being patients with Alzheimer's disease (AD). Psychogeriatric departments exist in hospitals, but there are almost no nursing homes and an insufficient number of daily care centres for PWD. Antidementia drugs registered in Croatia are donepezil, rivastigmine and memantine. Clinical studies of new antidementia drugs have been conducted in Croatia since 1989. At present, studies of several antidementia drugs are underway at different testing stages. PMID- 20307518 TI - Structural role of mismatched C-C bonds in a series of d-erythro-sphingomyelins as studied by DSC and electron microscopy. AB - A series of d-erythro (2S, 3R) sphingomyelins (SMs) whose acyl chain was 16, 18, 20, 22, and 24 carbons long, respectively, was synthesized by the acylation of d erythro-sphingosylphosphorylcholine. For all the SM dispersions, reversible and reproducible thermal behavior was observed to show the gel-to-gel and the main gel-to-liquid crystal phase transition in heating scan. The main transition enthalpy (DeltaH(M)) decreased linearly with increasing acyl chain length. The vesicular structures were observed for all the gel phases at temperatures just below the main transition, but the mean diameter of these vesicles changed markedly from approximately 1.5 to 100nm with increasing acyl chain length. On this basis, the decrease in DeltaH(M) with increasing acyl chain length was discussed from the viewpoint of the effect of the mismatched C-C bonds in the acyl chain on the van der Waals attractive force between the matched acyl chain segment and the sphingoshine chain of the gel phase at temperatures just below the main transition. PMID- 20307521 TI - Microalbumin screening. PMID- 20307520 TI - HDL in humans with cardiovascular disease exhibits a proteomic signature. AB - BACKGROUND: Alterations in protein composition and oxidative damage of high density lipoprotein (HDL) have been proposed to impair the cardioprotective properties of HDL. We tested whether relative levels of proteins in HDL(2) could be used as biomarkers for coronary artery disease (CAD). METHODS: Twenty control and eighteen CAD subjects matched for HDL-cholesterol, age, and sex were studied. HDL(2) isolated from plasma was digested with trypsin and analyzed by high resolution matrix-assisted laser desorption ionization mass spectrometry (MALDI MS) and pattern recognition analysis. RESULTS: Partial least squares discriminant analysis (PLS-DA) of mass spectra clearly differentiated CAD from control subjects with area under the receiver operating characteristic curve (ROC(AUC)) of 0.94. Targeted tandem mass spectrometric analysis of the model's significant features revealed that HDL(2) of CAD subjects contained oxidized methionine residues of apolipoprotein A-I and elevated levels of apolipoprotein C-III. A proteomic signature composed of MALDI-MS signals from apoA-I, apoC-III, Lp(a) and apoC-I accurately classified CAD and control subjects (ROC(AUC)=0.82). CONCLUSIONS: HDL(2) of CAD subjects carries a distinct protein cargo and that protein oxidation helps generate dysfunctional HDL. Moreover, models based on selected identified peptides in MALDI-TOF mass spectra of the HDL may have diagnostic potential. PMID- 20307522 TI - Alterations of insulin-like growth factor binding protein 3 (IGFBP-3) glycosylation in patients with breast tumours. AB - OBJECTIVES: Insulin-like growth factor binding protein-3 (IGFBP-3) is an important modulator of development and progression of breast cancer as it regulates the amount of free, physiologically active IGF-I and IGF-II. Changes in the glycosylation pattern within IGFBP-3 may affect its interaction with ligands. The aim of this study was to investigate whether such changes occur during disease progression. DESIGN AND METHODS: IGFBP-3 in serum samples from healthy women and from women with breast tumours was characterised in terms of its concentration (IRMA), glycosylation moiety (lectin-affinity chromatography) and distribution of molecular species (immunoblotting). RESULTS: In patients with benign tumours the concentration and carbohydrate content of IGFBP-3 was unaltered compared to healthy women. In patients with malignant tumours in most cases these two parameters were unchanged, but there were women whose concentration of IGFBP-3 was reduced and its structure was altered. In non surviving cancer patients the concentration of IGFBP-3 was significantly reduced and these molecules contained a greater amount of biantennary complex type N glycans having more mannose, fucose, bisecting GlcNAc and terminal sialic acid residues. CONCLUSION: Our results showed that breast cancer progression causes alterations of IGFBP-3 glycosylation. The extent of changes increases with breast cancer severity. PMID- 20307523 TI - Comparison of salivary cortisol and calculated free plasma cortisol during low dose ACTH test in healthy subjects. AB - OBJECTIVES: To compare free plasma cortisol (FPC) with salivary and calculated cortisol. DESIGN AND METHODS: FPC, salivary cortisol, free cortisol index (FCI), albumin-derived free cortisol index (FCIalb), Coolen's and Dorin's cortisol were assayed during repeated low-dose ACTH test in healthy women. RESULTS: FPC significantly correlated with its surrogates, the most with FCIalb and salivary cortisol. FPC and salivary cortisol showed the highest method agreement. CONCLUSIONS: FCIalb and salivary cortisol are preferred surrogates of FPC. PMID- 20307524 TI - Ayanin, a non-selective phosphodiesterase 1-4 inhibitor, effectively suppresses ovalbumin-induced airway hyperresponsiveness without affecting xylazine/ketamine induced anesthesia. AB - In recent in vitro reports, the IC(50) value of ayanin (quercetin-3,7,4'-O trimethylether) was 2.2microM for inhibiting interleukin (IL)-4 production from purified basophils, and its therapeutic ratio was >19. Therefore, we were interested in investigating the effects on ovalbumin induced airway hyperresponsiveness in vivo, and to clarify its potential for treating asthma. Ayanin (30-100micromol/kg, orally (p.o.)) dose-dependently and significantly attenuated the enhanced pause (P(enh)) value induced by methacholine in sensitized and challenged mice. It also significantly suppressed the increases in total inflammatory cells, macrophages, lymphocytes, neutrophils, and eosinophils, and levels of cytokines, including IL-2, IL-4, IL-5, and tumor necrosis factor (TNF)-alpha in bronchoalveolar lavage fluid of these mice. However, at 100micromol/kg, it significantly enhanced the level of interferon (IFN)-gamma. In addition, ayanin (30-100micromol/kg, p.o.) dose-dependently and significantly suppressed total and OVA-specific immunoglobulin (Ig)E levels in the serum and bronchoalveolar lavage fluid, and enhanced the IgG(2a) level in serum of these mice. In the present results, ayanin did not affect xylazine/ketamine-induced anesthesia, suggesting that ayanin has few or no adverse effects, such as nausea, vomiting, and gastric hypersecretion. In conclusion, the above results suggest that ayanin may have the potential for use in treating allergic asthma. PMID- 20307525 TI - Beta-asarone protection against beta-amyloid-induced neurotoxicity in PC12 cells via JNK signaling and modulation of Bcl-2 family proteins. AB - Neurodegenerative brain disorders such as Alzheimer's disease have been well investigated. However, significant methods for the treatment of the promotion and progression of Alzheimer's disease are unavailable to date. Apoptosis is a crucial pathway in neuronal loss in Alzheimer's disease patients. Thus, the suppression of apoptosis may be an effective therapeutic strategy for Alzheimer's disease. In this study, we evaluated the effect of beta-asarone on beta-amyloid (Abeta)-induced toxicity in cultured PC12 cells. Our data show significant induction of apoptosis in PC12 cells incubated with Abeta peptide, and this effect was reduced by beta-asarone. Beta-asarone reduced Abeta-induced JNK activation. In addition, beta-asarone attenuates Abeta-induced down-regulation of Bcl-w and Bcl-xL in a JNK-dependent manner, and subsequent inhibition mitochondrial release of cytochrome c and activation of caspase-3. Together, these findings indicate that Abeta-induced apoptosis of PC12 cells proceeds through mitochondrial pathway. Further, the JNK signaling cascade plays a role in regulating the anti-apoptotic effects of beta-asarone. Thus, our results indicate that beta-asarone might be a potentially therapeutic compound for Alzheimer's disease. PMID- 20307527 TI - Anti-fatigue effect of dicethiamine hydrochloride is likely associated with excellent absorbability and high transformability in tissues as a Vitamin B(1). AB - The anti-fatigue effect of dicethiamine hydrochloride (DCET) was assessed and compared to that of thiamine hydrochloride (VB(1)HCl) in rats. The absorbability and tissue distribution of thiamine after oral administration of DCET and VB(1)HCl were also examined. To create fatigued animals, male SD rats were placed in plastic cages containing 1.5cm of water for 5 consecutive days. The extent of fatigue was evaluated by a weight-loaded forced swimming test. After oral administration of DCET or VB(1)HCl to non-fatigued rats, blood and tissues were serially collected to determine the concentrations of thiamine and its phosphate esters. Pharmacokinetic analysis was performed to examine the thiamine profile in the body after administration of DCET or VB(1)HCl. Swimming time was significantly shorter for the fatigued vehicle group than the non-fatigued group. DCET (30 and 100mg/kg) significantly prolonged the swimming time compared to the fatigued vehicle group. The anti-fatigue effect of VB(1)HCl (70.1mg/kg) was not significant in our set of results. Both DCET and VB(1)HCl were rapidly absorbed into the circulating blood as thiamine and eventually became localized in the organs. Thiamine was distributed at higher concentrations to the blood, heart, thigh muscles, cerebellum, hippocampus, and thalamus after administration of DCET compared to VB(1)HCl. These results indicate that DCET is a vitamin B(1) derivative that has excellent absorbability and transformability in tissues and suggest that DCET as an oral therapy may be useful against combined mental and physical fatigue, such as that often encountered in contemporary society. PMID- 20307526 TI - Icariin exterts negative effects on human gastric cancer cell invasion and migration by vasodilator-stimulated phosphoprotein via Rac1 pathway. AB - Cellular movement is mainly orchestrated by actin-dependent cytoskeleton in which Rho GTPase Rac1 or vasodilator-stimulated phosphoprotein (VASP) closely collaborates. In the present in vitro study, we investigated the inhibitory effect and underlying molecular mechanism of icariin, a pure extract of the traditional Chinese medicine Herba epimedii, on the invasive and migration properties of human gastric cancer cell line BGC-823. At 50% growth-inhibiting concentration, icariin significantly suppressed tumor cells migration and invasion, which were traceable to down-regulation of Rac1 and VASP. Together with icariin, the selected siRNA targeting Rac1 or VASP reinforced these inhibitory effects. Rac1-siRNA-dependent down-regulation of Rac1 led to a large drop in VASP expression, whereas VASP-siRNA led to a slight fall in Rac1 expression, implying that the amount of Rac1 may influence VASP expression level. Moreover, transfection with Rac1 plasmids pcDNA3-EGFP-Rac1-Q61L led to the enhancement in expression level of both Rac1 and VASP. These results indicate that icariin exerts negative effects on tumor cell invasion and migration via the Rac1 dependent VASP pathway and may be a potential anti-cancer drug. PMID- 20307528 TI - Glucosamine regulation of LPS-mediated inflammation in human bronchial epithelial cells. AB - Inflammation is a complex process involving cytokine production to regulate host defense cascades in order to clear pathogenic agents. Upregulation of inflammatory cytokines, such as IL-6 and IL-8 by bacteria infection, occurs in pulmonary tissues and has been demonstrated to be critical to the lung inflammatory response. Glucosamine, primarily identified as an anti-arthritis supplement, has been also regarded as a potential anti-inflammatory agent. Thus we hypothesized that lipopolysaccharide (LPS) would activate IL-6 and IL-8 expressions in human primary bronchial epithelial cells and glucosamine could attenuate such an effect. The RT-PCR, real-time PCR, and ELISA analyses demonstrated that LPS-induced mRNAs encoding IL-6 and IL-8 and the subsequent secretion of IL-6 and IL-8 were inhibited by glucosamine treatment. MTT, alamarBlue, and annexin V apoptosis assays all suggested that this inhibition effect was not due to a cytotoxic effect mediated by glucosamine. Using the inhibitors of the MAP kinases and NFkappaB, it was revealed that p38, JNK and ERK, as well as NFkappaB, are all involved in LPS-induced IL-8 secretion; however only p38 is involved in LPS-induced IL-6 secretion. Immunoblot analysis further demonstrated that LPS-mediated phosphorylation of JNK and ERK, but not the LPS induced NFkappaB translocation, was inhibited by glucosamine. Altogether, our results indicate that glucosamine can potently suppress LPS-induced inflammatory cytokine expression, at least in part via attenuation of MAPK activation. PMID- 20307529 TI - Bradykinin-induced depolarisation and Ca(2+) influx through voltage-gated Ca(2+) channels in rat submucosal neurons. AB - The aim of the present study was the investigation of the mechanism, by which bradykinin B(2) receptor stimulation evokes an increase of the cytosolic Ca(2+) concentration in rat submucosal plexus. In ganglionic cells within the intact submucosal plexus, the Ca(2+)-response evoked by bradykinin was suppressed by Ni(2+), suggesting that Ca(2+) enters the cell through voltage-gated Ca(2+) channels (Ca(v) channels). Inhibition of Ca(v) channel subtypes P, T and R with omega-agatoxin IVA, flunarizine, and SNX-482 did not affect the response to bradykinin. In contrast, verapamil, omega-conotoxin GVIA, and omega-conotoxin MVIIC attenuated the actions of bradykinin, indicating the involvement of the L-, N- and Q-subtypes of Ca(v) channels. The combination of these three blockers had a strong inhibitory action on the bradykinin response. In order to study the mechanism of activation of Ca(v) channels by bradykinin, isolated submucosal neurons in culture were used. Immunocytochemical stainings revealed that these neurons expressed the bradykinin B(2) receptor, while the B(1) receptor was absent. Isolated submucosal glial cells did not express the bradykinin B(2) receptor. Whole-cell patch-clamp measurements of submucosal neurons showed that bradykinin induced a depolarisation of the membrane in average of 14mV. The ionic mechanism underlying the depolarisation was identified with current measurements at two different membrane potentials (-81 and 0mV). The current associated to Na(+) influx was not changed by bradykinin, whereas the current representing K(+) outflux was reduced by 26%. The present results suggest that at submucosal neurons from the rat colon bradykinin induces a depolarisation by decreasing the K(+) conductance, followed by activation of the Ca(v) channels, which mediates the increase of the cytosolic Ca(2+) concentration. PMID- 20307530 TI - Reversal of heparin-induced increases in aPTT in the rat by PM102, a novel heparin antagonist. AB - Protamine is the only agent approved to reverse heparin-induced anticoagulation. Due to the significant adverse effects of protamine there is an important need for an alternative agent with an improved safety profile. The pharmacodynamics of PM102, a novel peptide-based heparin antagonist, was evaluated and compared to protamine in a rat model. Rats were dosed with intravenous heparin (50U/kg) and 4min later with protamine (0.25, 0.75mg/kg single intravenous bolus) or PM102 (0.1, 0.3, 1, 3, 30mg/kg single intravenous bolus). Blood samples were collected though 60min for assessment of activated partial thromboplastin time (aPTT) and plasma concentration of PM102. Both doses of protamine markedly lowered the elevated aPTT to baseline values within 1 to 5min after administration. PM102 (0.3-30mg/kg) also rapidly and completely reversed heparin-induced increases in aPTT within 1 to 5min. The effects of PM102 administered as an infusion over 10min also reversed aPTT with similar potency to that observed for bolus administration. The onset of reversal with infusion was delayed relative to the same total dose given as a bolus; however, the maximum effect was similar. PM102 rapidly (T(max) 1-2.6min) appeared in plasma after dosing. Concentrations of PM102 generally declined rapidly after reaching T(max) with a mean T(1/2) of 4 to 31min. PM102 is a novel synthetic peptide that effectively reverses the anticoagulant effect of heparin. It's utility as a bolus injection as well as infusion, its rapid efficacy and its rapid clearance make this an ideal candidate for clinical development. PMID- 20307531 TI - Mutagenesis studies of neuropeptide S identify a suitable peptide tracer for neuropeptide S receptor binding studies and peptides selectively activating the I(107) variant of human neuropeptide S receptor. AB - Neuropeptide S and its receptor represent a novel neurotransmitter system mainly expressed in the brain. A single nucleotide polymorphism in the first extracellular loop (I107) increases the potency of neuropeptide S and has been identified for both the human neuropeptide S receptor short (A) and long (B) C terminal forms. Preliminary human genetic studies link this polymorphism to asthma, panic disorders and altered sleep behavior. No polymorphism or splice variants have been reported for the rat neuropeptide S receptor, however it carries an isoleucine at position 107. To identify a suitable tracer for neuropeptide S receptor binding and investigate the role of specific amino acids within neuropeptide S we carried out mutagenesis of the peptide and assessed the ability of the mutations to stimulate calcium release in HEK293 cells expressing human neuropeptide S receptor variants (A, B, AI(107), BI(107)) and rat neuropeptide S receptor. Replacement of threonine at position 8 by arginine and methionine at position 10 by tyrosine resulted in a mutant peptide slightly more potent on all neuropeptide S receptor variants compared to neuropeptide S and more importantly the iodinated mutant peptide was found to be a suitable tracer for binding studies with improved signal to noise ratio and stability compared to [(125)I-Y(10)] neuropeptide S. Replacement of serine at position 1 of neuropeptide S peptide by arginine resulted in a complete loss of potency for the neuropeptide S receptor (long and short form) but not for the I(107) receptor variants (long and short) or rat neuropeptide S receptor. PMID- 20307532 TI - Effect of the anti-diabetic drug metformin on bone mass in ovariectomized rats. AB - Recent studies have reported bone loss in the patients with diabetes and a direct osteogenic effect of metformin on osteoblast-like cells in culture. In this study, we investigated the action of metformin on bone mass in ovariectomized (OVX) rats. Three months after either a sham surgery or bilateral ovariectomy, thirty-two female Sprague-Dawley rats were randomly assigned into four groups: (1) Sham group; (2) OVX group; (3) OVX+metformin (50mg/kg/day) group; and (4) OVX+metformin (100mg/kg/day) group. After 2 months of oral administration with or without metformin, tibiae were harvested for dual energy X-ray absorptiometry, micro-computed tomography (micro-CT) and histology analysis, while the bone marrow cells from tibiae were collected for measurement of the mRNAs expressions for three osteoblast genes and estrogen receptors alpha by the use of real-time RT-PCR. We found that the impaired bone density and quality induced by bilateral ovariectomy were significantly improved by the treatment of metformin (both 50 and 100mg/kg/day), and this action could be partly mediated by regulating bone marrow cells development through induction of mechanisms regulating osteoblast markers core binding factor a1 and LDL receptor-related protein 5. These findings provide new evidence that the anti-diabetic drug metformin has a direct inhibition effect on bone loss in OVX rats, in addition to its well-documented osteogenic potency in vitro. PMID- 20307533 TI - Involvement of L-arginine-nitric oxide-cyclic guanosine monophosphate pathway in the antidepressant-like effect of bis selenide in the mouse tail suspension test. AB - The present study investigated a possible antidepressant-like effect of bis selenide by using the forced swimming and the tail suspension tests. The involvement of the l-arginine-nitric oxide-cyclic guanosine monophosphate signaling pathway in the antidepressant-like action of bis selenide was investigated. Bis selenide, given by oral route at doses of 0.5-5mg/kg, decreased the immobility time in the forced swimming and tail suspension tests. Pretreatment with l-arginine (750mg/kg, intraperitoneal, i.p., a nitric oxide precursor), sildenafil (5mg/kg, i.p., a phosphodiesterase 5 inhibitor) or S nitroso-N-acetyl-penicillamine (25microg/site, intracerebroventricular, i.c.v., a nitric oxide donor) reversed the reduction in the immobility time elicited by bis selenide (1mg/kg, p.o.) in the tail suspension test. Bis selenide (0.1mg/kg, p.o., a subeffective dose) produced a synergistic antidepressant-like effect with N(G)-nitro-L-arginine (0.3mg/kg, i.p., an inhibitor of nitric oxide synthase) or 7-nitroindazole (25mg/kg, i.p., a specific neuronal nitric oxide synthase inhibitor) in the tail suspension test. Pretreatment of animals with methylene blue (10mg/kg, i.p., an inhibitor of nitric oxide synthase and soluble guanylate cyclase) or 1H-[1,2,4] oxadiazolo [4,3-a]quinoxalin-1-one (30pmol, i.c.v., a specific inhibitor of soluble guanylate cyclase), at subeffective doses, caused a synergistic effect with bis selenide in the tail suspension test. Bis selenide (1mg/kg, p.o.), at an effective dose in the forced swimming and tail suspension tests, caused a significant decrease in the mouse cerebral nitrate/nitrite levels. The antidepressant-like effect of bis selenide in the tail suspension test is dependent on the inhibition of the L-arginine-nitric oxide-cyclic guanosine monophosphate pathway. PMID- 20307534 TI - The L-, N-, and T-type triple calcium channel blocker benidipine acts as an antagonist of mineralocorticoid receptor, a member of nuclear receptor family. AB - Aldosterone-induced activation of mineralocorticoid receptor, a member of the nuclear receptor family, results in increased tissue damage such as vascular inflammation and cardiac and perivascular fibrosis. Benidipine, a long-lasting dihydropyridine calcium channel blocker, is used for hypertension and angina. Benidipine exhibits pleiotropic pharmacological features such as renoprotective and cardioprotective effects through triple blockade of L-, N-, and T-type calcium channels. However, the mechanism of additional beneficial effects on end organ damage is poorly understood. Here, we examined the effects of benidipine and other calcium channel blockers on aldosterone-induced mineralocorticoid receptor activation using luciferase reporter assay system. Benidipine showed more potent activity than efonidipine, amlodipine, or azelnidipine. Benidipine depressed the response to higher concentrations of aldosterone, whereas pretreatment of eplerenone, a steroidal mineralocorticoid receptor antagonist, did not. Binding studies using [(3)H] aldosterone indicated that benidipine and other calcium channel blockers competed for binding to mineralocorticoid receptor. Benidipine and other calcium channel blockers showed antagonistic activity on Ser810 to Leu mutant mineralocorticoid receptor, which is identified in patients with early-onset hypertension. On the other hand, eplerenone partially activated the mutant. Results of analysis using optical isomers of benidipine indicated that inhibitory effect of aldosterone-induced mineralocorticoid receptor activation was independent of its primary blockade of calcium channels. These results suggested that benidipine directly inhibits aldosterone-induced mineralocorticoid receptor activation, and the antagonistic activity might contribute to the drug's pleiotropic pharmacological features. PMID- 20307535 TI - Radioligand binding characterization of the bradykinin B(2) receptor in the rabbit and pig ileal smooth muscle. AB - Several species-related differences have been reported in kinin B(2) receptor pharmacology. The present study aimed to evaluate the affinity of the bradykinin B(2) receptor antagonist MEN16132 for the rabbit and pig B(2) receptor, and radioligand binding experiments using [(3)H]bradykinin and membranes of rabbit and pig ileum smooth muscle were conducted. The [(3)H]bradykinin binding was characterized by homologous displacement curves indicating K(d) values of 0.65 and 0.33nM in rabbit and pig, respectively. The B(2) receptor specificity of [(3)H]bradykinin binding was shown by the low affinity (>microM) displayed by agonists ([desArg(9)]bradykinin and Lys[desArg(9)]bradykinin) and antagonists [Leu(8),desArg(9)]bradykinin and Lys[Leu(8),desArg(9)]bradykinin) selective for the B(1) receptor. The affinity of MEN16132 and other antagonists was determined by inhibition curves (pK(i) values in the rabbit and pig assay, respectively): MEN16132 (10.4 and 10.3) and peptide compounds such as icatibant (10.1 and 9.9) and MEN11270 (10.3 and 10.1) displayed subnanomolar potency in both assays; the nonpeptide LF16-0687 (8.4 and 8.5) and FR173657 (8.2 and 9.1) exhibited a different affinity pattern, whereas WIN64338 displayed low affinity (5.7 and or=7 microg/ml). The removing of the endothelium diminished the melittin-induced relaxation but did not affect the maximal contraction. The inhibition of prostaglandin and nitric oxide (NO) synthesis (by indomethacin and by N-omega-Nitro-l-arginine, respectively) and the use of K(+) channel inhibitors (apamin and charybdotoxin) showed that melittin evoked relaxation via an endothelium-dependent mechanism (NO production), and by activation of charybdotoxin-sensitive K(+) channels of smooth muscle. Apamin alone did not affect contraction or relaxation, but the inhibition of NO and prostanoid production revealed the involvement of apamin-sensitive K(+) channels of smooth muscle in melittin-induced relaxation. Our data show that melittin and apamin could affect contractility of porcine LAD at concentrations similar to those encountered in multiple honeybee stings in humans. Melittin could directly affect contractility of porcine LAD, whereas apamin acts as a modulator of the relaxant response to melittin. PMID- 20307564 TI - Vitamin B3, the nicotinamide adenine dinucleotides and aging. AB - Organism aging is a process of time and maturation culminating in senescence and death. The molecular details that define and determine aging have been intensely investigated. It has become appreciated that the process is partly an accumulation of random yet inevitable changes, but it can be strongly affected by genes that alter lifespan. In this review, we consider how NAD(+) metabolism plays important roles in the random patterns of aging, and also in the more programmatic aspects. The derivatives of NAD(+), such as reduced and oxidized forms of NAD(P)(+), play important roles in maintaining and regulating cellular redox state, Ca(2+) stores, DNA damage and repair, stress responses, cell cycle timing and lipid and energy metabolism. NAD(+) is also a substrate for signaling enzymes like the sirtuins and poly-ADP-ribosylpolymerases, members of a broad family of protein deacetylases and ADP-ribosyltransferases that regulate fundamental cellular processes such as transcription, recombination, cell division, proliferation, genome maintenance, apoptosis, stress resistance and senescence. NAD(+)-dependent enzymes are increasingly appreciated to regulate the timing of changes that lead to aging phenotypes. We consider how metabolism, specifically connected with Vitamin B3 and the nicotinamide adenine dinucleotides and their derivatives, occupies a central place in the aging processes of mammals. PMID- 20307566 TI - The role of vitamin E and oxidative stress in diabetes complications. AB - Diabetes is a disease characterized by poor glycemic control for which risk of the type 2 form increases with age. A rise in blood glucose concentration causes increased oxidative stress which contributes to the development and progression of diabetes-associated complications. Studies have shown that primary antioxidants or genetic manipulation of antioxidant defenses can at least partially ameliorate this oxidative stress and consequentially, reduce severity of diabetic complications in animal models. Data from humans is less clear and will be summarized in this review. We highlight results from studies performed to investigate the role of vitamin E in preventing diabetes-induced oxidative damage in cell culture, animal models, and human participants, and summarize evidence testing whether this nutrient has an effect on outcomes related to the diabetic complications of nephropathy, retinopathy, and neuropathy. The most compelling evidence for an effect of vitamin E in diabetes is on protection against lipid peroxidation, whereas effects on protein and DNA oxidation are less pronounced. More studies are required to make definitive conclusions about the effect of vitamin E treatment on diabetes complications in human subjects. PMID- 20307567 TI - Acute exercise reverses aged-induced impairments in insulin signaling in rodent skeletal muscle. AB - The insulin resistance associated with aging is improved by exercise, but the molecular mechanisms of this improvement are not fully understood. We investigated whether the improvement in insulin action, associated with acute exercise in old rats is dependent on the modulation of pIRS-1Ser307, JNK, IkBalpha and PTP-1B. Aging rats were subjected to swimming for two 1.5-h long bouts, separated by a 45min rest period. Sixteen hours after the exercise, the rats were killed and proteins from the insulin signaling pathway were analyzed by immunoblotting. Our results show that the reduction in glucose disappearance rate (Kitt), observed in aged rats, was restored at 16h after exercise. Aging led to an increase in Ser307 phosphorylation of IRS-1, and this was reversed by exercise in the skeletal muscle, in parallel with a reduction in pJNK and IkBalpha degradation. Moreover, aging induced an increase in the expression of PTP-1B and attenuated insulin signaling in the muscle of rats, a phenomenon that was reversed by exercise. Interestingly, the decrease in PTP-1B expression in the muscle of exercised old rats was accompanied by an increase in SIRT1 expression. These results provide new insights into the mechanisms by which exercise restores insulin sensitivity during aging. PMID- 20307568 TI - Colorectal cancer screening adherence is higher with fecal immunochemical tests than guaiac-based fecal occult blood tests: a randomized, controlled trial. AB - OBJECTIVES: Determine whether colorectal cancer screening adherence is greater with fecal immunochemical tests (FIT) or guaiac-based fecal occult blood tests (gFOBT). METHODS: We used electronic health records to identify 3869 New Mexico Veterans Affairs Health Care System primary care patients due for screening in 2008 for whom fecal blood testing was appropriate. We invited randomly selected patients by mail to participate in a study comparing FIT and gFOBT. We randomly allocated 404 subjects to receive FIT (n=202) or gFOBT (n=202) by mail. We determined the proportion of subjects completing testing within 90days of agreeing to participate in the study. We also used multivariate logistic regression to evaluate screening completion, adjusting for age, gender, race/ethnicity, clinic site, previous gFOBT testing, and co-morbidity. RESULTS: Screening adherence was higher with FIT than gFOBT (61.4% vs. 50.5%, P=0.03). The adjusted odds ratio for completing FIT vs. gFOBT was 1.56, 95% CI 1.04, 2.32. CONCLUSION: In a clinic setting of patients who were due for colorectal cancer screening, adherence was significantly higher with FIT than gFOBT. PMID- 20307565 TI - Mitochondrial DNA alterations and reduced mitochondrial function in aging. AB - Oxidative damage to mitochondrial DNA increases with aging. This damage has the potential to affect mitochondrial DNA replication and transcription which could alter the abundance or functionality of mitochondrial proteins. This review describes mitochondrial DNA alterations and changes in mitochondrial function that occur with aging. Age-related alterations in mitochondrial DNA as a possible contributor to the reduction in mitochondrial function are discussed. PMID- 20307569 TI - A novel conjugative plasmid from Enterococcus faecalis E99 enhances resistance to ultraviolet radiation. AB - Enterococcus faecalis has emerged as a prominent healthcare-associated pathogen frequently encountered in bacteremia, endocarditis, urinary tract infection, and as a leading cause of antibiotic-resistant infections. We recently demonstrated a capacity for high-level biofilm formation by a clinical E. faecalis isolate, E99. This high biofilm-forming phenotype was attributable to a novel locus, designated bee, specifying a pilus at the bacterial cell surface and localized to a large approximately 80 kb conjugative plasmid. To better understand the origin of the bee locus, as well as to potentially identify additional factors important to the biology and pathogenesis of strain E99, we sequenced the entire plasmid. The nucleotide sequence of the plasmid, designated pBEE99, revealed large regions of identity to the previously characterized conjugative plasmid pCF10. In addition to the bee locus, pBEE99 possesses an open reading frame potentially encoding aggregation substance, as well as open reading frames putatively encoding polypeptides with 60% to 99% identity at the amino acid level to proteins involved in regulation of the pheromone response and conjugal transfer of pCF10. However, strain E99 did not respond to the cCF10 pheromone in clumping assays. While pBEE99 was found to be devoid of any readily recognizable antibiotic resistance determinants, it carries two non-identical impB/mucB/samB-type genes, as well as genes potentially encoding a two-component bacteriocin similar to that encoded on pYI14. Although no bacteriocin activity was detected from an OG1RF transconjugant carrying pBEE99 against strain FA2-2, it was approximately an order of magnitude more resistant to ultraviolet radiation. Moreover, curing strain E99 of this plasmid significantly reduced its ability to survive UV exposure. Therefore, pBEE99 represents a novel conjugative plasmid that confers biofilm-forming and enhanced UV resistance traits that might potentially impact the virulence and/or fitness of E. faecalis. PMID- 20307570 TI - Circadian clock genes: non-circadian roles in sleep, addiction, and psychiatric disorders? AB - Elucidation of the cellular and molecular mechanisms of the circadian clock, along with the realization that these mechanisms are operative in both central and peripheral tissues, has revolutionized circadian biology. Further, these observations have resulted in an explosion of interest in the health implications of circadian organization and disorganization at both molecular and physiological levels. Thus, recent research has implicated mutations and polymorphisms of circadian clock genes in diabetes and obesity, cardiovascular disease, and cancer. At the neuro-behavioral level, circadian clock genes have also been implicated in sleep disorders, drug and alcohol addiction, and other psychiatric conditions. While such findings are frequently described as revealing "non circadian" effects of clock genes, it remains possible that most of these non circadian effects are in fact secondary to the loss of cellular and systemic rhythmicity. This review summarizes the evidence linking circadian clock genes to biobehavioral dysregulation, and considers criteria for defining a pleiotropic clock gene effect as non-circadian. PMID- 20307571 TI - Outcomes of cryptococcal meningitis in antiretroviral naive and experienced patients in South Africa. PMID- 20307572 TI - Mycobacterium chelonae valve endocarditis resulting from contaminated biological prostheses. AB - OBJECTIVES: A rapid-growing mycobacteria biological prosthetic valve (BPV) endocarditis related to prosthetic manufacturing process is described in Brazil. METHODS: From 1999 to 2008, thirty-nine patients underwent BPV replacement due to culture-negative suspected endocarditis. All these cases had histological sections stained by Ziehl-Neelsen method. Clinical and microbiological data were reviewed in all acid-fast bacilli (AFB) positive cases. The 16S-23S internal transcribed sequence (ITS) was amplified using DNA extracted from paraffin embedded samples, digested with restrictions enzymes and/or sequenced. RESULTS: Eighteen AFB positive BPV (18/39)(46%) were implanted in 13 patients and were from the same manufacturer. Four of them were implanted in other hospitals. Thirteen BPV were histologically proven endocarditis and five showed a colonization pattern. The examination of six non-implanted "sterile" BPV from this manufacturer resulted in 5 AFB positive. Mycobacterium chelonae was the AFB identified by ITS restriction analysis and sequencing. CONCLUSIONS: Rapid-growing mycobacteria infections must be suspected and Ziehl-Neelsen stain always performed on histology of either early or late BPV endocarditis, particularly when blood cultures are negative. PMID- 20307573 TI - Establishment of cell-based reporter system for diagnosis of poxvirus infection. AB - Poxvirus detection assays are based on morphology, viral antigens and specific nucleic acids, none of which indicates virus viability or infectious capacity. Determination of virus viability is achieved by propagation in cell cultures and subsequent analysis by the mentioned methods, a process that takes days. Thus, presented here the development of a new assay, named PILA (Poxvirus Infection Luciferase Assay), for rapid detection of infectious poxviruses which is a cell based reporter assay. The assay is composed of two steps: (i) Transfection of cells with a poxvirus specific reporter vector which consists of the early 7.5 kDa-STR promoter, regulating the expression of luciferase gene; (ii) Infection with a poxvirus containing sample. Luciferase activity measured post infection, indicates the presence of infectious poxvirus in the sample. The assay can detect quantities as low as 100 PFU of VACV, six hours post infection. Orthopox virus universality was confirmed by detection of various Orthopoxviruses, and specificity was verified by using pox-specific neutralizing antibodies. The PILA is specific, rapid, simple, and suitable for detecting viable virus. The assay can be utilized for applications such as poxvirus titration, neutralizing assay and drug discovery. The assay was adjusted for live detection assay by using GFP as reporting gene. PMID- 20307574 TI - Priming with a DNA vaccine and boosting with an inactivated vaccine enhance the immune response against infectious bronchitis virus. AB - The methods of repeated immunization with inactivated vaccines have been used widely to increase antibody protection against infectious bronchitis virus (IBV). However, compared with DNA vaccines, these methods usually induce poor cellular responses. In the present study, specific pathogen-free (SPF) chickens were immunized intramuscularly with a DNA vaccine carrying the main IBV structural genes (pVAX1-S1, pVAX1-M, and pVAX1-N, respectively) and boosted with the IBV M41 strain inactivated vaccine to assess whether such a new strategy could enhance the immune responses against IBV. The protection efficacy of the DNA vaccine carrying different structural genes for priming was evaluated further. The chickens were immunized primely on day 7 and boosted 2 weeks later. After that, distribution of the DNA vaccine in vivo, the percentage of CD4+CD3+ and CD8+CD3+ subgroups of peripheral blood T-lymphocytes, and the specific IgG and virus neutralizing antibodies were measured. Chickens were then challenged by the nasal ocular route with the IBV M41 strain 4 weeks after booster immunization. The results demonstrated that priming with a DNA vaccine encoding nucleocapsid protein (pVAX1-N) and boosting with the inactivated IBV vaccine led to the dramatic augmentation of humoral and cellular responses, and provided up to 86.7% rate of immune protection, providing an effective approach to protect chickens from IBV. PMID- 20307575 TI - Optimisation of reverse transcriptase loop-mediated isothermal amplification assay for rapid detection of Macrobrachium rosenbergii noda virus and extra small virus in Macrobrachium rosenbergii. AB - The standardisation and optimisation of a one step single tube reverse transcriptase loop-mediated isothermal amplification (RT-LAMP) procedure is described for rapid diagnosis of white tail disease, a viral disease caused by Macrobrachium rosenbergii noda virus (MrNV) and extra small virus (XSV), in giant fresh water prawn, M. rosenbergii. Time, temperature and quantity of each reagent were optimised for the detection of the two viruses. This method was more sensitive than the conventional reverse transcriptase polymerase chain reaction (RT-PCR) for detecting the two viruses. The RT-LAMP reaction is highly suited for disease diagnosis in developing countries. Amplification of DNA can be detected without the use of agarose gel electrophoresis, by the production of a whitish precipitate of magnesium pyrophosphate as a by-product. The cost of RT-LAMP for one reaction is nearly 4 times less than that of RT-PCR. PMID- 20307576 TI - Simple construction of chimeric hairpin RNA for virus resistance in plants. AB - RNA silencing has been adopted to develop virus-resistant plants through expression of virus-derived hairpin RNAs. Due to the high sequence specificity of RNA silencing, this technology has been limited to the targeting of single viruses. Simultaneous targeting of multiple viruses or plant genes can be achieved by using a chimeric cassette. In this study, a simple method was developed to construct chimeric hairpin RNA rapidly and efficiently. This method splices two DNA fragments from viruses or plant genes to be a chimeric sequence using Overlap Extension PCR (OE-PCR); then this chimeric sequence was assembled with an intron sequence to generate an intron-containing hairpin RNA construct in one step mediated by OE-PCR. This method is neither dependent on restriction enzymes nor requires expensive consumables, so a chimeric hairpin RNA can be constructed rapidly and costlessly. Two chimeric hairpin RNA constructs were amplified successfully using this method, with the targeting sequences from both papaya ringspot virus (PRSV) and two plant genes encoding translation initiation factors eIF4E and eIFiso4E. This novel method is a useful strategy to construct chimeric hairpin RNA for RNA silencing in plants. PMID- 20307577 TI - Dengue virus replicons: production of an interserotypic chimera and cell lines from different species, and establishment of a cell-based fluorescent assay to screen inhibitors, validated by the evaluation of ribavirin's activity. AB - The prevention and treatment of flavivirus infections are public health priorities. Dengue fever is the most prevalent mosquito-borne viral disease of humans, affecting more than 50 million people annually. Despite the urgent need to control dengue infections, neither specific antiviral therapies nor licensed vaccines exist and the molecular basis of dengue pathogenesis is not well understood. In this study we produced a novel dengue virus type 2 (DV2) subgenomic replicon that expresses a fusion protein comprised of Enhanced Green Fluorescent Protein (EGFP) and Puromycin N-Acetyltransferase (PAC). We successfully established BHK, COS and Huh7 cell lines that stably expressed the DV2 replicon. Using EGFP as a reporter of DV replication complex activity, we set up a new HTS assay. The assay was validated using the inhibitor ribavirin, confirmed by flow cytometry analysis and the analysis of NS5 expression by Western-blot analysis. In order to develop a system to test antivirals against the NS5 proteins of all four DV serotypes in a similar cellular environment, the replicon was further modified, to allow easy exchange of the NS5 gene between DV serotypes. As proof of principle, a chimeric replicon in which the DV2 NS5 gene was substituted with that of DV type 3 was stably expressed in BHK cells and used in ribavirin inhibition studies. The assays described in this study will greatly facilitate DV drug discovery by serving as primary or complementary screening. The approach should be applicable to the development of fluorescent cell-based HTS assays for other flaviviruses, and useful for the study of many aspects of DV, including viral replication and pathogenesis. PMID- 20307578 TI - Lipophile-conjugated sulfated oligosaccharides as novel microbicides against HIV 1. AB - With the aim of providing compounds suitable for further development as microbicides active against human immunodeficiency virus 1 (HIV-1) a library containing 37 lipophile-conjugated sulfated oligosaccharides was screened for antiviral and virucidal activity against this virus. Four highly active compounds had low drug inhibition concentrations (IC(50)) for HIV-1 and inactivated viral particles, suggestive of virucidal properties. Two of these compounds comprising a sulfated tetrasaccharide linked to a cholestanol group by a glycosidic bond, showed low toxicity and high selectivity indices. The two compounds were active both against CCR5 and dual-tropic CCR5/CXCR4 clinical HIV-1 isolates. Since herpes simplex virus type 2 (HSV-2) may be a cofactor for HIV-1 infection, the virucidal effect of the compounds was demonstrated against both viruses when mixed and incubated together on permissive cells. Incubation of compounds with serum, and to a lesser degree, cervical secretions, reduced the HIV-1 inactivating capacity, which suggests the need for molecular modification to reduce host protein binding. Considering the virucidal effect and low toxicity, these sulfated oligosaccharides with lipophilic tails may offer new possibilities of microbicide development. PMID- 20307579 TI - Slow binding-tight binding interaction between benzimidazol-2-one inhibitors and HIV-1 reverse transcriptase containing the lysine 103 to asparagine mutation. AB - Novel benzimidazol-2-one non-nucleoside reverse transcriptase inhibitors (NNRTIs) have been recently identified, through rational structure-based molecular modeling and docking approaches, as highly effective inhibitors of the wild type and drug-resistant HIV-1 reverse transcriptase (RT). These compounds also showed potent anti-HIV activities against viral strains, superior to the clinically approved NNRTI efavirenz. However, they were still of limited efficacy towards the K103N mutant. Here we report a detailed enzymatic analysis elucidating the molecular mechanism of interaction between benzimidazol-2-one derivatives and the K103N mutant RT. The loss of potency of these molecules towards the K103N RT was specifically due to a reduction of their association rate to the enzyme. Unexpectedly, these compounds showed a strongly reduced dissociation rate from the K103N mutant, as compared to the wild type enzyme, suggesting that, once occupied by the drug, the mutated binding site could achieve a more stable interaction with these molecules. The characterization of this slow binding-tight binding mutant-specific mechanism of interaction may pave the way to the design of more effective new generation benzimidazol-2-one NNRTIs with promising drug resistant profile and minimal toxicity. PMID- 20307581 TI - Regional metabolic alteration of Alzheimer's disease in mouse brain expressing mutant human APP-PS1 by 1H HR-MAS. AB - This study aimed to find the most sensitive brain region of APP-PS1 mice in early stage Alzheimer's disease (AD) and to compare the findings with wild-type mouse brain using (1)H high resolution magic angle spectroscopy (HR-MAS). At 18 and 35 weeks of age, the object recognition test was performed with both APP-PS1 and wild-type mice, and the metabolite concentrations were measured in six brain regions at 38-42 weeks using (1)H HR-MAS. Compared to that of wild-type mice, the memory index of the APP-PS1 mice at 18 weeks was not significantly different; however, the memory index of the APP-PS1 mice at 35 weeks was significantly lower. Similar to the results of the (1)H HR-MAS, the [N-acetyl aspartate (NAA)+acetate (Acet)] level in APP-PS1 mice was decreased in the hippocampus and temporal cortex, and the myo-inositol (mIns) level was increased in the entire brain. In addition, scyllo-inositol (sIns) was also elevated in the frontal, occipital, and parietal cortices, hippocampus and thalamus. These findings demonstrated that the behavioral abnormalities of the APP-PS1 mice started at about 30 weeks of age and that the hippocampus and temporal cortex were the most sensitive regions during early-stage AD. In addition, the results of this study confirmed that an increase of mIns and sIns precedes the reduction of the NAA level. These findings demonstrated that the metabolism of the APP-PS1 mouse was associated with early-stage AD. Furthermore, the regional neurochemical profile of APP-PS1 mouse can be used to investigate the pathophysiological mechanisms associated with AD. PMID- 20307580 TI - Compounds that target host cell proteins prevent varicella-zoster virus replication in culture, ex vivo, and in SCID-Hu mice. AB - Varicella-zoster virus (VZV) replicates in quiescent T cells, neurons, and skin cells. In cultured fibroblasts (HFFs), VZV induces host cyclin expression and cyclin-dependent kinase (CDK) activity without causing cell cycle progression. CDK1/cyclin B1 phosphorylates the major viral transactivator, and the CDK inhibitor roscovitine prevents VZV mRNA transcription. We investigated the antiviral effects of additional compounds that target CDKs or other cell cycle enzymes in culture, ex vivo, and in vivo. Cytotoxicity and cell growth arrest doses were determined by Neutral Red assay. Antiviral effects were evaluated in HFFs by plaque assay, genome copy number, and bioluminescence. Positive controls were acyclovir (400 microM) and phosphonoacetic acid (PAA, 1 mM). Test compounds were roscovitine, aloisine A, and purvalanol A (CDK inhibitors), aphidicolin (inhibits human and herpesvirus DNA polymerase), l-mimosine (indirectly inhibits human DNA polymerase), and DRB (inhibits casein kinase 2). All had antiviral effects below the concentrations required for cell growth arrest. Compounds were tested in skin organ culture at EC(99) doses; all prevented VZV replication in skin, except for aloisine A and purvalanol A. In SCID mice with skin xenografts, roscovitine (0.7 mg/kg/day) was as effective as PAA (36 mg/kg/day). The screening systems described here are useful models for evaluating novel antiviral drugs for VZV. PMID- 20307582 TI - Neurochemical and behavioral effects elicited by bupropion and diethylpropion in rats. AB - This study is an attempt to demonstrate whether bupropion (BP) and diethylpropion (DEP) exert their pharmacological actions by similar neurochemical mechanisms in the dorsal striatum. In this regard, the release of dopamine (DA), glutamate (Glu), and GABA, was determined in the rat dorsal striatum after acute (5 min) and chronic (15 consecutive days) treatments, and subsequently correlated with the locomotor activities produced by these drugs. The results from the acute experiments indicate that BP and DEP (40 mg/kg) increase locomotor activity, whereas chronic DEP treatment decreases locomotor activity by unspecific mechanisms. Acute BP treatment produces significant DA and Glu, but not GABA, releases. A lesser extent of DA release and tissue content of DA and its metabolites, and consequently less locomotor activity, was observed after chronic BP treatment. Acute DEP (5mg/kg) was only able to slightly increase DA release and to decrease the tissue levels of DA, but no other markers, with practically nil locomotor activity, whereas chronic DEP produced even less neurotransmitter release. The observed difference between BP and DEP might be based on that although both drugs inhibit the DA and norepinephrine transporters, the BP induced nicotinic receptor inhibition has yet to be demonstrated for DEP. PMID- 20307583 TI - A computational theory of episodic memory formation in the hippocampus. AB - A quantitative computational theory of the operation of the hippocampus as an episodic memory system is described. The CA3 system operates as a single attractor or autoassociation network to enable rapid, one-trial associations between any spatial location (place in rodents or spatial view in primates) and an object or reward and to provide for completion of the whole memory during recall from any part. The theory is extended to associations between time and object or reward to implement temporal order memory, also important in episodic memory. The dentate gyrus performs pattern separation by competitive learning to produce sparse representations, producing for example neurons with place-like fields from entorhinal cortex grid cells. The dentate granule cells produce by the very small number of mossy fibre connections to CA3 a randomizing pattern separation effect important during learning but not recall that separates out the patterns represented by CA3 firing to be very different from each other, which is optimal for an unstructured episodic memory system in which each memory must be kept distinct from other memories. The direct perforant path input to CA3 is quantitatively appropriate to provide the cue for recall in CA3, but not for learning. The CA1 recodes information from CA3 to set up associatively learned backprojections to neocortex to allow subsequent retrieval of information to neocortex, providing a quantitative account of the large number of hippocampo neocortical and neocortical-neocortical backprojections. Tests of the theory including hippocampal subregion analyses and hippocampal NMDA receptor knockouts are described and support the theory. PMID- 20307584 TI - Dorsolateral prefrontal cortex specifically processes general - but not personal knowledge deception: Multiple brain networks for lying. AB - Despite intensive research into ways of detecting deception in legal, moral and clinical contexts, few experimental data are available on the neural substrate for the different types of lies. We used transcranial direct current stimulation (tDCS) to modulate dorsolateral prefrontal cortex (DLPFC) function and to assess its influence on various types of lies. Twenty healthy volunteers were tested before and after tDCS (anodal and sham). In each session the Guilty Knowledge Task and Visual Attention Task were administered at baseline and immediately after tDCS ended. A computer-controlled task was used to evaluate truthful responses and lie responses to questions referring to personal information and general knowledge. Dependent variables collected were reaction times (RTs) and accuracy. At baseline the RTs were significantly longer for lies than for truthful responses. After sham stimulation, lie responses remained unchanged (p = 0.24) but after anodal tDCS, RTs decreased significantly only for lies involving general knowledge (p = 0.02). tDCS left the Visual Attention Task unaffected. These findings show that manipulating DLPFC function with tDCS specifically modulates deceptive responses for general information leaving those on personal information unaffected. Multiple cortical networks intervene in deception involving general and personal knowledge. Deception referring to general and personal knowledge probably involves multiple cortical networks. PMID- 20307585 TI - Regular voluntary exercise cures stress-induced impairment of cognitive function and cell proliferation accompanied by increases in cerebral IGF-1 and GST activity in mice. AB - Chronic stress impairs cognitive function and hippocampal neurogenesis. This impairment is attributed to increases in oxidative stress, which result in the accumulation of lipid peroxide. On the other hand, voluntary exercise enhances cognitive function, hippocampal neurogenesis, and antioxidant capacity in normal animals. However, the effects of voluntary exercise on cognitive function, neurogenesis, and antioxidants in stressed mice are unclear. This study was designed to investigate whether voluntary exercise cures stress-induced impairment of cognitive function accompanied by improvement of hippocampal neurogenesis and increases in antioxidant capacity. Stressed mice were exposed to chronic restraint stress (CRS), which consisted of 12h immobilization daily and feeding in a small cage, for 8 weeks. Exercised mice were allowed free access to a running wheel during their exposure to CRS. At the 6th week, cognitive function was examined using the Morris water maze (MWM) test. Daily voluntary exercise restored stress-induced impairment of cognitive function and the hippocampal cell proliferation of newborn cells but not cell survival. Voluntary exercise increased insulin-like growth factor 1 (IGF-1) protein and mRNA expression in the cerebral cortex and liver, respectively. In addition, CRS resulted in a significant increase in the number of 4-hydrosynonenal (4-HNE)-positive cells in the hippocampal dentate gyrus; whereas, voluntary exercise inhibited it and enhanced glutathione s-transferases (GST) activity in the brain. These findings suggest that voluntary exercise attenuated the stress-induced impairment of cognitive function accompanied by improvement of cell proliferation in the dentate gyrus. This exercise-induced improvement was attributed to exercise induced enhancement of IGF-1 protein and GST activity in the brain. PMID- 20307586 TI - Acute and repeated stress differentially regulates behavioral, endocrine, neural parameters relevant to emotional and stress response in young and aged rats. AB - Aging is associated with dysregulation of emotional and endocrine responses in a stressful environment. To understand the developmental mechanisms of stress vulnerability with aging, we investigated the effects of repeated stress on behavioral, endocrine, and neural parameters relating to emotional and stress responses in young (3 months old) and aged (24 months old) F344/N male rats. Young and aged rats were either subjected to 1-h restraint stress for 14 consecutive days or left undisturbed. After the procedures, behaviors were examined in open-field and elevated plus-maze tests to evaluate the level of anxiety induced by aging and repeated stress. Following the behavioral tests, serum corticosterone concentrations and c-Fos immunoreactivity throughout the brain in response to acute restraint stress were examined. Control and repeatedly stressed aged rats showed more anxiety-related behaviors than control and repeatedly stressed young rats in both tests. In particular, repeatedly stressed aged rats showed more anxiety-related behaviors in the elevated plus-maze than control aged and repeatedly stressed young rats, although stressed young rats were not different from control young rats. Repeatedly stressed aged rats showed higher serum corticosterone concentrations in response to acute stress than subjects in all other conditions. In c-Fos expression, control aged rats showed decreases in c-Fos-positive cells in response to acute stress in the prefrontal cortex, medial preoptic area, bed nucleus of the stria terminalis, nucleus accumbens, medial amygdaloid nucleus, and CA3 subfield of hippocampus, whereas they showed increases in the dorsal raphe nucleus and parvocellular part of the paraventricular nucleus of the hypothalamus compared to acutely stressed control young rats. These results indicate that repeated stress enhances emotional and stress responses in aged rats but not in young rats, suggesting that aging causes organisms to become vulnerable to stress, which might be mediated by dysfunction of the brain system regulating emotional and stress responses. PMID- 20307587 TI - Prenatal oxycodone exposure impairs spatial learning and/or memory in rats. AB - Recent changes in demographic patterns of drug use have resulted in the increased non-medical use of prescription opiates. These users are younger and more likely to be female, which has the potential for increasing rates of in utero exposure. Therefore, we developed a rat model that simulates a prescription opiate dependent woman who becomes pregnant. Adult female Sprague-Dawley rats were treated for 30 days via oral gavage with ascending doses of oxycodone HCl up to a final dose of 15mg/kg/day, which was maintained during breeding and gestation. Controls were treated with water. The adult male offspring of these treated dams were tested on the radial arm maze, the Morris water maze (with a short and a long intertrial interval), and a spatial T-maze. Prenatal oxycodone exposure led to a deficit in the radial arm maze characterized by a greater number of reference memory errors, especially in the beginning of testing. In contrast, in the T-maze, prenatal oxycodone-exposed rats learned the task as well as well as the prenatal water controls. However, they had a modest deficit in retention of the task when assessed 5 days after acquisition training ended. For the Morris water maze, the intertrial interval affected the pattern of learning. While there was no deficit when the training had a short intertrial interval, when there was a long intertrial interval, prenatal oxycodone-exposed rats had poorer acquisition. The spatial learning deficit was characterized by and increased latency to find and a greater distance traveled to the platform in the prenatal oxycodone-exposed rats. These data were corroborated by analysis of the behavioral search strategy, which showed a decreased use of spatial strategies and an increase in non-spatial strategies, especially wall-hugging, in prenatal oxycodone-exposed rats as compared to prenatal water control rats on day 2 of acquisition. These results indicate that prenatal oxycodone exposure consistently impairs learning and memory in a battery of spatial tasks. PMID- 20307588 TI - The Leishmania mexicana A600 genes are functionally required for amastigote replication. AB - Leishmania parasites, the causative agent of leishmaniasis, have a digenetic lifecycle consisting of the morphologically distinct insect vector stage (promastigote) and the mammalian infective amastigote stage. Differentiation of promastigotes to the amastigote stage involves significant morphological and biochemical changes, however, very few genes have been characterised as being differentially expressed in the two stages. The Leishmania A600 genes are one of the few gene families that exhibit stage-specific expression and, as such, they are of interest as potential virulent factors. In this study, we characterize the A600 family in several Leishmania species and investigate their role in amastigote differentiation and proliferation. Four open reading frames, A600-1, A600-2, A600-3, and A600-4, were identified at the multi-gene L. mexicana A600 locus via cloning and restriction mapping. Homology searching identified A600 homologues in other Leishmania species, L. major, L. braziliensis and L. infantum but not in the closely related Trypanosoma family. A targeted gene deletion approach was utilized to determine the cellular function of the L. mexicanaA600 genes. A600(-/-) promastigotes differentiated to axenic amastigotes in response to temperature shift and acidification of culture media, but showed significant growth arrest. Similarly, during in vitro macrophage infection studies, A600(-/-) promastigotes established an early infection, but were deficient in their ability to proliferate as intracellular amastigotes. The ability of A600(-/-) amastigotes to proliferate in mouse peritoneal macrophages was restored by re-introduction of the A600-1 gene, but not the A600-4 gene. The results from these experiments show that the A600-1 gene is essential for continued proliferation of amastigotes, and potentially for development of chronic leishmaniasis. Furthermore, these results suggest a potential role for the L. mexicana A600-deficient mutant as a vaccine candidate. PMID- 20307589 TI - Ligation of beta4 integrins activates PKB/Akt and ERK1/2 by distinct pathways relevance of the keratin filament. AB - In normal epithelial cells hemidesmosomes mediate stable adhesion to the underlying basement membrane. In carcinoma cells a functional and spatial dissociation of the hemidesmosomal complex is observed stimulating the hypothesis that the beta4 integrin may trigger essential signalling cascades determining cell fate. In the present study we dissected the signalling pathways giving rise to PKB/Akt and ERK1/2 activation in response to beta4 ligation by 3E1. It was found that the activation of PKB/Akt is sensitive towards alterations of the keratin filament as demonstrated by using KEB-7 cells that carry a keratin mutation typical for epidermolysis bullosa simplex. Similar results were achieved by chemically induced keratin aggregations. Of note, the signalling to ERK1/2 was not affected. ERK1/2 activation utilizes an EGF-R transactivation mechanism as shown by dominant-negative expression experiments and also by treatment with a specific inhibitor (AG1478). Downstream from the EGF-R the activation of ERK1/2 takes the prototypical signalling cascade via Shc, Ras and Raf-1 as demonstrated by dominant-negative expression experiments. Taken together our data define a new model of beta4-dependent PKB/Akt and ERK1/2 activation demonstrating the keratin filament as a structure necessary in signal transmission. PMID- 20307591 TI - Carrier induced epitopic suppression of antibody responses induced by virus-like particles is a dynamic phenomenon caused by carrier-specific antibodies. AB - Pre-existing immunity against vaccine carrier proteins has been reported to inhibit the immune response against antigens conjugated to the same carrier by a process termed carrier induced epitopic suppression (CIES). Hence understanding the phenomenon of CIES is of major importance for the development of conjugate vaccines. Virus-like particles (VLPs) are a novel class of potent immunological carriers which have been successfully used to enhance the antibody response to virtually any conjugated antigen. In the present study we investigated the impact of a pre-existing VLP-specific immune response on the development of antibody responses against a conjugated model peptide after primary, secondary and tertiary immunization. Although VLP-specific immune responses led to reduced peptide-specific antibody titers, we showed that CIES against peptide-VLP conjugates could be overcome by high coupling densities, repeated injections and/or higher doses of conjugate vaccine. Furthermore we dissected VLP-specific immunity by adoptively transferring VLP-specific antibodies, B-cells or T(helper) cells separately into naive mice and found that the observed CIES against peptide VLP conjugates was mainly mediated by carrier-specific antibodies. PMID- 20307592 TI - Cross-reactive antibody responses to the 2009 A/H1N1v influenza virus in the Italian population in the pre-pandemic period. AB - To assess in Italy the pre-pandemic susceptibility of the general population to the 2009 A/H1N1v influenza virus, 587 serum samples collected in 2004 were analyzed using haemagglutination-inhibition (HI), single-radial-haemolysis (SRH) and microneutralisation (MN) assays. Serum samples were stratified by age group, gender, and geographic area. Overall, using HI assay, the proportion of subjects showing antibodies cross-reacting with 2009 A/H1N1v virus at seroprotection level (>or=1:40) was estimated to be 6.7%, 12.4%, and 22.4% in individuals born between 2004 and 1949, 1948 and 1939, 1938 and 1909, respectively. With a HI antibody titre of >or=1:10, in the same birth cohort, the seroprotection levels were 13.5%, 19.2%, and 58.2%, respectively. The results suggest that the Italian population was not fully naif to the current pandemic virus and that the possible previous exposure and immune response increases with age. PMID- 20307593 TI - A new subunit vaccine based on nucleoprotein nanoparticles confers partial clinical and virological protection in calves against bovine respiratory syncytial virus. AB - Human and bovine respiratory syncytial viruses (HRSV and BRSV) are two closely related, worldwide prevalent viruses that are the leading cause of severe airway disease in children and calves, respectively. Efficacy of commercial bovine vaccines needs improvement and no human vaccine is licensed yet. We reported that nasal vaccination with the HRSV nucleoprotein produced as recombinant ring-shaped nanoparticles (N(SRS)) protects mice against a viral challenge with HRSV. The aim of this work was to evaluate this new vaccine that uses a conserved viral antigen, in calves, natural hosts for BRSV. Calves, free of colostral or natural anti-BRSV antibodies, were vaccinated with N(SRS) either intramuscularly, or both intramuscularly and intranasally using Montanide ISA71 and IMS4132 as adjuvants and challenged with BRSV. All vaccinated calves developed anti-N antibodies in blood and nasal secretions and N-specific cellular immunity in local lymph nodes. Clinical monitoring post-challenge demonstrated moderate respiratory pathology with local lung tissue consolidations for the non-vaccinated calves that were significantly reduced in the vaccinated calves. Vaccinated calves had lower viral loads than the non-vaccinated control calves. Thus N(SRS) vaccination in calves provided cross-protective immunity against BRSV infection without adverse inflammatory reaction. PMID- 20307590 TI - Hedgehog signaling and gastrointestinal cancer. AB - Hedgehog (Hh) signaling is critical for embryonic development and in differentiation, proliferation, and maintenance of multiple adult tissues. De regulation of the Hh pathway is associated with birth defects and cancer. In the gastrointestinal tract, Hh ligands Sonic (Shh) and Indian (Ihh), as well as the receptor Patched (Ptch1), and transcription factors of Glioblastoma family (Gli) are all expressed during development. In the adult, Shh expression is restricted to the stomach and colon, while Ihh expression occurs throughout the luminal gastrointestinal tract, its expression being highest in the proximal duodenum. Several studies have demonstrated a requirement for Hh signaling during gastrointestinal tract development. However to date, the specific role of the Hh pathway in the adult stomach and intestine is not completely understood. The current review will place into context the implications of recent published data related to the biochemistry and cell biology of Hh signaling on the luminal gastrointestinal tract during development, normal physiology and subsequently carcinogenesis. PMID- 20307594 TI - An in vitro assay system as a potential replacement for the histamine sensitisation test for acellular pertussis based combination vaccines. AB - The histamine sensitisation test (HIST) for pertussis toxin is currently an official batch release test for acellular pertussis containing combination vaccines in Europe and North America. However, HIST, being a lethal endpoint assay, often leads to repeated tests due to large variations in test performance. Although a more precise HIST test based on measurement of temperature reduction after the histamine challenge is used in Asian countries, this test still uses animals. An in vitro test system based on a combination of enzyme coupled-HPLC and carbohydrate-binding assays with results analysed by a mathematical formula showed a good agreement with the in vivo HIST results based on measurement of temperature reduction after histamine challenge. The new in vitro test system was shown to be a potential alternative to the current in vivo HIST. PMID- 20307595 TI - Comparison of egg and high yielding MDCK cell-derived live attenuated influenza virus for commercial production of trivalent influenza vaccine: in vitro cell susceptibility and influenza virus replication kinetics in permissive and semi permissive cells. AB - Currently MedImmune manufactures cold-adapted (ca) live, attenuated influenza vaccine (LAIV) from specific-pathogen free (SPF) chicken eggs. Difficulties in production scale-up and potential exposure of chicken flocks to avian influenza viruses especially in the event of a pandemic influenza outbreak have prompted evaluation and development of alternative non-egg based influenza vaccine manufacturing technologies. As part of MedImmune's effort to develop the live attenuated influenza vaccine (LAIV) using cell culture production technologies we have investigated the use of high yielding, cloned MDCK cells as a substrate for vaccine production by assessing host range and virus replication of influenza virus produced from both SPF egg and MDCK cell production technologies. In addition to cloned MDCK cells the indicator cell lines used to evaluate the impact of producing LAIV in cells on host range and replication included two human cell lines: human lung carcinoma (A549) cells and human muco-epidermoid bronchiolar carcinoma (NCI H292) cells. The influenza viruses used to infect the indicators cell lines represented both the egg and cell culture manufacturing processes and included virus strains that composed the 2006-2007 influenza seasonal trivalent vaccine (A/New Caledonia/20/99 (H1N1), A/Wisconsin/67/05 (H3N2) and B/Malaysia/2506/04). Results from this study demonstrate remarkable similarity between influenza viruses representing the current commercial egg produced and developmental MDCK cell produced vaccine production platforms. MedImmune's high yielding cloned MDCK cells used for the cell culture based vaccine production were highly permissive to both egg and cell produced ca attenuated influenza viruses. Both the A549 and NCI H292 cells regardless of production system were less permissive to influenza A and B viruses than the MDCK cells. Irrespective of the indicator cell line used the replication properties were similar between egg and the cell produced influenza viruses. Based on these study results we conclude that the MDCK cell produced and egg produced vaccine strains are highly comparable. PMID- 20307596 TI - Production and efficacy of an Aeromonas hydrophila recombinant S-layer protein vaccine for fish. AB - A recombinant protein for the S-layer protein of Aeromonas hydrophila was produced and its ability to protect common carp Cyprinus carpio L. against six virulent isolates of A. hydrophila was assessed. A group of 120 carp (30-40 g) were vaccinated intra-peritoneally with 0.1 ml of adjuvanted vaccine (30 microg protein per fish). Another group of 120 carp were injected with 0.1 ml of PBS adjuvant mixture to serve as controls. Twenty fish from each group were challenged with each one of six virulent isolates of A. hydrophila 35 days post vaccination. The fish were maintained in 12 separate tanks before terminating the experiment at 16 days post-challenge. The relative percentage survival (RPS) for the six isolates of A. hydrophila ranged from 56 to 87%. The difference in survival rate of fish challenged with four of the isolates was statistically significant in vaccinated fish compared to control fish, when analysed using a Chi-square test. The results of the study suggest that the recombinant S-layer protein of A. hydrophila could be useful as a vaccine antigen to protect fish against different isolates of this pathogenic bacterium. PMID- 20307597 TI - VP5-deficient mutant virus induced protection against challenge with very virulent infectious bursal disease virus of chickens. AB - A mutant infectious bursal disease virus (IBDV) deficient in expressing VP5, rGx F9VP2DeltaVP5, was generated using reverse genetics technology. In comparison to the characteristics of rGx-F9VP2 virus in vitro, the mutant virus demonstrated lower viral titer and cytopathogenicity. To understand the role of VP5 in the pathogenicity of IBDV in vivo, animal experiments were conducted. rGx F9VP2DeltaVP5 caused reduced bursal lesion of SPF chickens compared to rGx-F9VP2. Although rGx-F9VP2DeltaVP5 induced lower serum antibody than rGx-F9VP2 did, both inoculated groups were fully protected against vvIBDV challenge 4 weeks post inoculation. In addition, immunosuppression induced by VP5-deficient virus was studied in 2-week-old SPF chickens immunized with AIV inactivated vaccine. And there was reduced immunosuppression as shown in our experimental results. The results showed that AIV hemagglutination inhibition (HI) antibodies of the rGx F9VP2DeltaVP5 inoculated group were similar to those of the mock-inoculated group, however, they were higher than those of the rGx-F9VP2 inoculated group, indicating that deficiency of VP5 decreased the immunosuppression of rGx F9VP2DeltaVP5 in chickens. All data indicated that VP5 played an important role in viral replication and pathogenesis both in vitro and in vivo. The VP5 deficient mutant virus could be a good candidate as a marked vaccine. PMID- 20307598 TI - Effects of long-time reading experience on reaction time and the recognition potential. AB - The proposition that long-time experience in reading a language gradually builds up rapidly acting neural processes that facilitate the processing of words in that language and speed them into conscious awareness was examined. Behavioral reaction time (RT) and electrophysiological responsiveness to visually displayed words and non-language images were measured in persons who differed in how much experience they had in reading English. The electrophysiological response was the recognition potential (RP). Behavioral RT and the latency of the RP to English words were both expected to depend upon how much English reading experience a person had. The short latency of the RP was expected to free it from the influence of non-perceptual factors that affect RT, such as speed/accuracy tradeoff. This expectation yielded the prediction that the behavioral and electrophysiological results would differ in a specific way. Long-time readers of English were expected to show shorter RP latency to English words than less experienced (China-educated) readers of English but no RP latency difference for non-language images, with which neither group had greater experience. In contrast, due to speed accuracy tradeoff, the China-educated subjects were expected to show longer RT for both the words and the non-language images. The prediction was confirmed. The amount of language experience that a person had showed a stronger relationship to RP latency than it did to RT. This helped to validate the use of the RP as a tool for investigating perception and demonstrated definite advantages that it has for studying acquired perceptual processes in humans. PMID- 20307599 TI - Improved tumor-targeting drug delivery and therapeutic efficacy by cationic liposome modified with truncated bFGF peptide. AB - Fibroblast growth factor receptors (FGFRs), overexpressed on the surface of a variety of tumor cells and on tumor neovasculature in situ, are potential targets for tumor- and vascular-targeting therapy. This study aimed to develop a FGFR mediated drug delivery system to target chemotherapeutic agents to FGFR overexpressed tumor cells and tumor neovasculature endothelial cells in vitro and in vivo. Here we designed a truncated human basic fibroblast growth factor peptide (tbFGF), which was attached to the surface of cationic liposomal doxorubicin (LPs-DOX) and paclitaxel (LPs-PTX) via electrostatic force. Then we characterized the tbFGF-modified liposome (tbFGF-LPs) and examined internalization of doxorubicin in tumor cells (TRAMP-C1, B16) and HUVEC cells in vitro. In vivo, we evaluated the biodistribution and antitumor efficacy of tbFGF LPs-DOX and tbFGF-LPs-PTX in C57BL/6J mice bearing TRAMP-C1 prostate carcinoma and B16 melanoma, respectively. The tbFGF-LPs-DOX significantly improved the uptake of doxorubicin in TRAMP-C1, B16 and HUVEC cells, respectively. Biodistribution study in B16 tumor-bearing mice showed that tbFGF-LPs-PTX achieved 7.1-fold (72.827+/-7.321mgh/L vs 10.292+/-0.775mgh/L, mean+/-SD, P<0.01) accumulation of paclitaxel in tumor tissue than those of free paclitaxel. More importantly, treatment of tumor-bearing mice with tbFGF-LPs-DOX and tbFGF-LPs-PTX showed the significant inhibition in tumor growth and improvement in survival rate as compared with mice treated with free and liposomal drugs in TRAMP-C1 and B16 tumor models, respectively. Furthermore, repeated intravenous administration of tbFGF-LPs-DOX/PTX did not induce anti-bFGF antibodies. These results suggested that this FGFR-mediated drug delivery system may provide a new treatment strategy for tumors which overexpress FGFRs. PMID- 20307600 TI - The selective impact of chocolate craving on visuospatial working memory. AB - The present study aimed to extend previous research into cognitive impairments as a consequence of food craving. In particular, the study examined the impact of chocolate craving on the three components of working memory: the phonological loop, the visuospatial sketchpad, and the central executive, assessed by the digit span, Corsi blocks, and the double span tasks, respectively. A sample of 96 female undergraduate students was randomly assigned to a craving or control condition. Participants in the craving condition abstained from eating chocolate for 24h prior to testing, and performed the cognitive tasks in the presence of chocolate, a manipulation that successfully elicited chocolate cravings. As predicted on the basis of the visual imagery nature of food cravings, participants in the craving condition performed more poorly on the Corsi blocks task than control participants, but the groups did not differ on the digit span or double span measures. These results indicate that chocolate cravings selectively disrupt performance on visuospatial tasks. According to the working memory model, this occurs because food cravings compete for limited visuospatial working memory resources. These findings have practical implications in that visuospatial memory plays an important role in many everyday behaviours. PMID- 20307601 TI - Induction of apoptosis by plant natriuretic peptides in rat cardiomyoblasts. AB - Atrial natriuretic peptide (ANP) has an important role in maintaining the homeostasis of body fluids and blood pressure and also in preventing cardiac hypertrophy and initiating the process of apoptosis. An immunoreactive analog of ANP was discovered in plants over a decade ago and termed plant natriuretic peptide (PNP). PNP is a small protein that contains sequence and structural similarity to ANP within a predicted protruding psi (psi) loop. Since application of ANP or PNP stimulates similar functional effects in plants, it is conceivable that PNP may have effects on mammalian cells. In this report, we show that purified recombinant PNP induces apoptosis in a dose dependent and cell type specific manner. Rat cardiac myoblasts (H9c2 cells) were more susceptible to the apoptotic promoting effects of PNP and ANP than HEK-293T cells where PNP had a protective effect at lower concentrations. Similarly rat thoracic myoblasts (A 10) were less responsive to both PNP and ANP than the H9c2 cells. Since PNP is mimicking the effect of ANP in this instance, PNP may prove to be a useful lead molecule for developing novel therapeutic natriuretic peptides. PMID- 20307602 TI - Structure and function relationship of toxin from Chinese scorpion Buthus martensii Karsch (BmKAGAP): gaining insight into related sites of analgesic activity. AB - In this study, an effective Escherichia coli expression system was used to study the role of residues in the antitumor-analgesic peptide from Chinese scorpion Buthus martensii Karsch (BmKAGAP). To evaluate the extent to which residues of the toxin core contribute to its analgesic activity, nine mutants of BmKAGAP were obtained by PCR. Using site-directed mutagenesis, all of these residues were individually substituted by one amino acid. These were then subjected to a circular dichroism analysis, and an analgesic activity assay in mice. This study represents a thorough mapping and elucidation of the epitopes that underlie the molecular basis of the analgesic activity. The three-dimensional structure of BmKAGAP was established by homology modeling. Our results revealed large mutant dependent differences that indicated important roles for the studied residues. With our ongoing efforts for establishing the structure and analgesic activity relationship of BmKAGAP, we have succeeded in pinpointing which residues are important for the analgesic activity. PMID- 20307603 TI - Inhibition of L-type calcium currents by salusin-beta in rat cardiac ventricular myocytes. AB - Salusin-beta is a new regulatory peptide relevant to the cardiovascular system and exerts negative inotropic effect on ventricular muscle. The purpose of the present study was to determine whether salusin-beta can inhibit cardiac L-type calcium channel current (I(Ca,L)). Using whole-cell voltage-clamp techniques, I(Ca,L) was measured in ventricular myocytes isolated from 12 to 16 weeks rats. Salusin-beta dose-dependently and reversibly reduced the magnitude of I(Ca,L) in rat ventricular myocytes. Neither threshold potential nor the peak potential of current-voltage relationship was affected. Salusin-beta increased the rate of I(Ca,L) inactivation without altering its gating properties. These results suggest salusin-beta inhibited I(Ca,L) by increasing the rate of I(Ca,L) inactivation and the inhibition of L-type Ca(2+) channels induced by salusin-beta may contribute to its negative inotropic effect on ventricular muscle. PMID- 20307604 TI - Surgery and sepsis increase somatostatin-like immunoreactivity in the human plasma. AB - We have previously shown in animals that somatostatin released from capsaicin sensitive afferents in response to inflammation and tissue damage exerts systemic anti-nociceptive and anti-inflammatory actions. Since peptidergic sensory innervation of the airways and the joints are particularly dense, we aimed at investigating the alterations of plasma somatostatin-like immunoreactivity (SST LI) in response to thoracic and orthopedic surgery, as well as sepsis. Thoracotomy, video-assisted thoracoscopy, hip and knee endoprosthesis were performed under general anesthesia. Blood was taken before, during and after the surgical procedures, as well as at admission and every consecutive morning from septic patients receiving exclusively total parenteral nutrition. SST-LI was determined from the plasma with specific and sensitive radioimmunoassay developed in our laboratory. Plasma SST-LI in healthy volunteers and preoperatively was 8 12fmol/ml. Both thoracotomy and thoracoscopy significantly increased SST-LI by 55 60% at the end of the procedures when the thoracic cavity and the skin were closed. Hip endoprosthesis implantation elevated SST-LI by 30% after skin incision, which increased further to 55% by the time the surgery was completed. In contrast, knee operations performed under tourniquet did not alter SST-LI in the systemic circulation. SST-LI was almost 3-fold higher in the plasma of septic patients than in healthy volunteers. This human study revealed that thoracic/hip surgery and sepsis elevate SST-LI in the systemic circulation, presumably by inducing its release from sensory fibres. It is concluded, that the endogenous protective mechanism mediated by neural somatostatin, which has been evidenced in animals, is likely to operate in patients. PMID- 20307605 TI - Pharmacological profile and antiparkinsonian properties of the novel nociceptin/orphanin FQ receptor antagonist 1-[1-cyclooctylmethyl-5-(1-hydroxy-1 methyl-ethyl)-1,2,3,6-tetrahydro-pyridin-4-yl]-3-ethyl-1,3-dihydro-benzoimidazol 2-one (GF-4). AB - In this study we provided a pharmacological characterization of the recently synthesized nociceptin/orphanin FQ (N/OFQ) peptide receptor (NOP) antagonist 1-[1 Cyclooctylmethyl-5-(1-hydroxy-1-methyl-ethyl)-1,2,3,6-tetrahydro-pyridin-4-yl]-3 ethyl-1,3-dihydro-benzoimidazol-2-one (GF-4) and investigated its antiparkinsonian properties. GF-4 inhibited N/OFQ binding to CHO(hNOP) cell membranes (pK(i) 7.46), and antagonized N/OFQ effects in a calcium mobilization assay and electrically stimulated isolated tissues (pK(B) 7.27-7.82), showing a approximately 5-fold selectivity over classical opioid receptors. In vivo, GF-4 dually modulated stepping activity in wild-type mice, causing facilitation in the 0.01-10mg/kg dose range and inhibition at 30mg/kg. These effects were mediated by NOP receptors since GF-4 was ineffective in NOP receptor knock-out mice. Antiparkinsonian properties of GF-4 were investigated in 6-hydroxydopamine hemilesioned rats. GF-4 ameliorated akinesia, bradykinesia and overall gait ability in the 0.1-10mg/kg dose range, but inhibited motor activity at 30mg/kg. To investigate the circuitry underlying motor facilitating and inhibitory effects of GF-4, microdialysis coupled to behavioral testing (akinesia test) was performed. An anti-akinetic dose of GF-4 (1mg/kg) reduced glutamate (GLU) and enhanced GABA release in SNr, while the pro-akinetic dose of GF-4 (30mg/kg) evoked opposite effects. Moreover, the anti-akinetic dose of GF-4 reduced GABA and increased GLU release in ventro-medial thalamus, the pro-akinetic dose decreasing GABA without affecting GLU release in this area. We conclude that GF-4 is an effective NOP receptor antagonist able to attenuate parkinsonian-like symptoms in vivo via inhibition of the nigro-thalamic pathway. PMID- 20307606 TI - Novel conopeptides in a form of disulfide-crosslinked dimer. AB - In our present work, seven conotoxins and conopeptides were cloned from four cone snail species based on the M-superfamily signal peptides. Among them, two conopeptides, Vt3.1 and Vt3.2, showed unusual sequence characteristics. Both of them contained two cysteines that are separated by just one non-cysteine residue. In vitro, the chemically synthesized Vt3.1 formed dimers with different intermolecular disulfide linkages. Only the dimer with crossed disulfides showed bioactivity when injected into the intraventricular region of mice brains. Therefore, Vt3.1 and Vt3.2 represent a new group of conopeptides that form disulfide-crosslinked dimers in vitro and probably in vivo. PMID- 20307607 TI - Changed salt appetite and central angiotensin II-induced cellular activation in rat offspring following hypoxia during fetal stages. AB - Hypoxia in pregnancy may induce fetal growth restriction and cause functional abnormalities during development. The present study determined the long-term influence of hypoxia in fetal life on dipsogenic behavior linked to central angiotensin (Ang) network in the offspring rats. Fetal blood pO(2) and body weight were decreased by hypoxia during pregnancy, followed by a postnatal "catch up" growth. Subcutaneous hypertonic saline or intracerebroventricular Ang II significantly increased salt intake in the offspring prenatally exposed to hypoxia, while water intake was the same between the two groups. Ang II-induced c fos expression was detected in the paraventricular nuclei, median preoptic nuclei, supraoptic nuclei, and subfornical organ in the brain, in association with reduced forebrain AT(2) receptor protein abundance in the offspring prenatally exposed to hypoxia. Levels of central AT(1) receptor protein were not changed between the two groups. Hypoxia during pregnancy could be linked to developmental problems related to behavioral dysfunctions in body fluid regulations in later life, in association with the change in central angiotensin II-mediated neural activation and expression of the Ang II receptor in the brain. PMID- 20307608 TI - A novel cyclopeptide from the cyclization of PACAP(1-5) with potent activity towards PAC1 attenuates STZ-induced diabetes. AB - The N-terminal deletion of pituitary adenylate cyclase-activating polypeptide (PACAP)(1-5) generates its own antagonist. The cyclopeptide C*HSDGIC*, which results from the cyclization of PACAP(1-5) with disulfide, was designed and synthesized. CHO cells expressing a PAC1 N/R splice variant (PAC1-CHO) were used to detect the potent activation of PAC1 by C*HSDGIC*. In vitro cell assays showed that C*HSDGIC* stimulated cAMP production and increased the viability of PAC1-CHO cells at micromolar concentrations, about 1000 fold that of PACAP. PACAP(6-38) blocked the effects of PACAP on the proliferation of PAC1-CHO cells but did not interfere with the effects of C*HSDGIC*, suggesting that the activation of PAC1 by C*HSDGIC* was independent of the binding of PAC1 to the C-terminus of PACAP. In experiments in vivo, 10mumol/kg C*HSDGIC* decreased the plasma glucose level, increased the plasma insulin level and improved glucose tolerance significantly (P<0.01) when co-injected with STZ for 5 days. The results of these in vitro and in vivo studies of the biological characteristics of C*HSDGIC* reveal that it is a potent activator of PAC1. PMID- 20307609 TI - Peptidergic modulation of serotonin and nerve elicited responses of the salivary duct muscle in the snail, Helix pomatia. AB - In the present study, the ability of a range of endogenous neuropeptides to modulate neuromuscular transmission was examined in the salivary duct neuromuscular preparation of the terrestrial snail, Helix pomatia. Immunohistochemical and physiological techniques were used to localize the neuropeptides (GSPYFVamide, CARP, FMRFamide and APGWamide) and to investigate whether contractions elicited by the stimulation of the salivary nerve or by exogenously applied 5-HT are subject to peptidergic modulation. All of the neuropeptides studied decreased the tonus by a direct action on the muscle fibers in a concentration dependent manner in a range of 10(-9) to 10(-6)M. Neuropeptides distinctly affected the 5-HT evoked contraction or relaxation and GSPYFVa and APGWa decreased also the amplitude of contractions elicited by the stimulation of the salivary nerve. All four neuropeptides facilitated the relaxation phase providing further evidence for the postsynaptic action of neuropeptides. Low Ca(2+)/high Mg(2+) saline abolished the nerve-elicited contractions, however the denervated muscle retained the ability to contract due to the mobilization of the Ca(2+) from intracellular stores. It was concluded, that peptides belonging to different peptide families exerted their effects through pre- and postsynaptic mechanisms. The modulatory effect of neuropeptides can be assigned to the partial co-localization of 5-HT and neuropeptides in the nerves innervating muscles of the salivary duct, as it was demonstrated by double labeling immunohistochemistry. A double origin of the 5-HTergic innervation was demonstrated, including efferents originating from both the cerebral and visceral ganglia. PMID- 20307610 TI - Antidepressant-like or anxiolytic-like actions of topiramate alone or co administered with intra-lateral septal infusions of neuropeptide Y in male Wistar rats. AB - We tested the effects of intra-lateral septal infusions of neuropeptide Y (NPY) combined with systemic injections of topiramate in the DRL-72s paradigm and the elevated plus-maze test in male Wistar rats. Intra-lateral septal infusions of desipramine (5.0 microg/microl; P<0.05) or intra-lateral septal infusions of NPY (3.0 microg/microl, P<0.05; 3.5 microg/microl, P<0.05) or systemic injections of topiramate (20.0mg/kg, P<0.05; 30.0mg/kg, P<0.05) or subthreshold doses of topiramate (10.0mg/kg) combined with intra-lateral septal infusions of subthreshold doses of NPY (2.5 microg/microl; P<0.05) induced a dose-dependent increase in reinforced lever presses and a cohesive rightward shift of the inter response time distribution in the DRL 72s task. In the elevated plus-maze test, intra-lateral septal infusions of NPY (3.0 microg/microl, P<0.05; 3.5 microg/microl, P<0.05) or midazolam (10.0 microg/microl; P<0.05) or systemic injections of topiramate (20.0mg/kg, P<0.05; 30.0mg/kg, P<0.05) or subthreshold doses of systemic injections of topiramate (10.0mg/kg) combined with intra lateral septal infusions of subthreshold doses of NPY (2.5 microg/microl; P<0.05) increased the exploration of the open arms without affecting locomotion. In conclusion, intra-septal NPY has anxiolytic effects in the EPM, and antidepressant effects in the DRL 72s test. Similarly, systemic topiramate has anxiolytic effects in the EPM, and antidepressant effects in the DRL 72s test. Finally, a combination of subthreshold doses of NPY and topiramate together also have anxiolytic and antidepressant effects, suggesting a synergistic effect. PMID- 20307611 TI - Endogenous orexin-A modulates gastric motility by peripheral mechanisms in rats. AB - Orexin-A (OXA) and orexin receptor type 1 (OX1R) are found in enteric nervous system and smooth muscle cells in the digestive tract. Fasting is a stimulant for OXA synthesis. The aim of the present study was to investigate central and peripheral effects of endogenous OXA on gastric motility. Endogenous OXA synthesis was induced by 36h fasting. Vagotomy was used to evaluate N.vagus mediated effects of OXA. Gastric emptying and interdigestive gastric motility were measured by spectrophotometric and manometric methods, respectively. Rats were pretreated with OX1R antagonist SB-334867 prior to measurements. Plasma OXA concentration was assayed with radioimmunoassay while preproorexin (PPO) expression was determined with Western blotting in gastric and hypothalamic tissues. OXA immunoreactivity in antrum was determined with immunohistochemistry. Plasma OXA level, PPO protein expression and OXA immunoreactivity were significantly increased in response to 36h fasting. Endogenous OXA facilitated gastric emptying and inhibited gastric interdigestive motility. As these effects were abolished with SB-334867, it is likely that gastrokinetic effects of OXA are mediated via OX1R. Vagotomy did not alter OXA-mediated effects. According to current data, OXA is up-regulated both centrally and peripherally upon fasting. Endogenous OXA accelerates gastric emptying while it inhibits interdigestive motility. PMID- 20307612 TI - Depolarizing stimuli cause persistent and selective loss of orexin in rat hypothalamic slice culture. AB - A hypothalamic neuropeptide orexin (hypocretin) is a critical regulator of physiological processes including sleep/wakefulness and feeding. Using organotypic slice culture of rat hypothalamus, we found that exposure to elevated extracellular concentration of K(+) (+10-30 mM) for 24-72h led to a substantial decrease in the number of neurons immunoreactive for orexin and a co-existing neuropeptide dynorphin-A. In contrast, the same treatment affected neither the number of melanin-concentrating hormone-immunoreactive neurons nor the number of total neurons. A substantial decrease of orexin-immunoreactive neurons was also induced by 72h treatment with 1-10 microM veratridine, a Na(+) channel activator. The effect of elevated K(+) was only partially reversible, and that of veratridine was virtually irreversible, although the decrease in orexin immunoreactivity was not associated with signs of cell damage assessed by propidium iodide uptake and Hoechst 33342 nuclear staining. In addition, the level of preproorexin mRNA did not decrease during treatment with elevated K(+) or veratridine. After treatment with elevated K(+) and veratridine, c-Fos immunoreactivity appeared in orexin-immunoreactive neurons but not in melanin concentrating hormone-immunoreactive neurons, suggesting selective excitation of orexin neurons. However, the amount of orexin released extracellularly was paradoxically decreased by treatment with elevated K(+) and veratridine. Overall, these characteristics of orexin neurons may be taken into consideration to understand the behaviors of these neurons under physiological and pathophysiological conditions. PMID- 20307613 TI - Peripherally injected CCK-8S activates CART positive neurons of the paraventricular nucleus in rats. AB - Cholecystokinin (CCK) plays a role in the short-term inhibition of food intake. Cocaine- and amphetamine-regulated transcript (CART) peptide has been observed in neurons of the paraventricular nucleus (PVN). It has been reported that intracerebroventricular injection of CART peptide inhibits food intake in rodents. The aim of the study was to determine whether intraperitoneally (ip) injected CCK-8S affects neuronal activity of PVN-CART neurons. Ad libitum fed male Sprague-Dawley rats received 6 or 10 microg/kg CCK-8S or 0.15M NaCl ip (n=4/group). The number of c-Fos-immunoreactive neurons was determined in the PVN, arcuate nucleus (ARC), and the nucleus of the solitary tract (NTS). CCK-8S dose-dependently increased the number of c-Fos-immunoreactive neurons in the PVN (mean+/-SEM: 102+/-6 vs. 150+/-5 neurons/section, p<0.05) and compared to vehicle treated rats (18+/-7, p<0.05 vs. 6 and 10 microg/kg CCK-8S). CCK-8S at both doses induced an increase in the number of c-Fos-immunoreactive neurons in the NTS (65+/-13, p<0.05, and 182+/-16, p<0.05). No effect on the number of c-Fos neurons was observed in the ARC. Immunostaining for CART and c-Fos revealed a dose dependent increase of activated CART neurons (19+/-3 vs. 29+/-7; p<0.05), only few activated CART neuron were observed in the vehicle group (1+/-0). The present observation shows that CCK-8S injected ip induces an increase in neuronal activity in PVN-CART neurons and suggests that CART neurons in the PVN may play a role in the mediation of peripheral CCK-8S's anorexigenic effects. PMID- 20307614 TI - Src tyrosine kinase regulates angiotensin II-induced protein kinase Czeta activation and proliferation in vascular smooth muscle cells. AB - Protein kinase Czeta (PKCzeta) isoform plays a critical role in angiotensin II (AngII)-elicited extracellular signal-regulated kinase 1/2 (ERK1/2) activation and proliferation in vascular smooth muscle cells (VSMCs). However, the exact signal transduction mechanism by which AngII activates PKCzeta has not been clarified. In this study, we investigated the role of Src in PKCzeta activation and VSMCs proliferation induced by AngII. AngII-induced rapid activation of PKCzeta, which was associated with its phosphorylation and nuclear translocation. AngII not only induced Src activation but also promoted the physical association between Src and PKCzeta, which was abolished by Src inhibition with PP2. Src inhibition also abrogated AngII-stimulated PKCzeta activation, ERK1/2 phosphorylation and VSMCs proliferation. In conclusion, Src kinase plays an important role in AngII-elicited PKCzeta activation and the subsequent downstream signaling including ERK1/2 activation and VSMCs proliferation. PMID- 20307615 TI - NGF-induced moesin phosphorylation is mediated by the PI3K, Rac1 and Akt and required for neurite formation in PC12 cells. AB - Moesin is a member of ERM family proteins which act as the cross-linkers between plasma membrane and actin-cytoskeleton and is activated by phosphorylation at Thr 558. In neurons, suppression of radixin and moesin alters the growth cone morphology. However, the significance of phosphorylation of ERM proteins in neuronal cells has not been fully investigated. In this study, we studied the signaling pathways responsible for moesin phosphorylation and its functional importance in NGF-treated PC12 cells. NGF rapidly induced the phosphorylation of moesin at Thr-558 in PC12 cells which was dependent on PI3K and Rac1. We found that Akt interacted and phosphorylated with moesin both in vitro and in vivo. Inhibition of PI3K and Rac1 abolished the NGF-induced Akt activation, indicating that Akt is at the downstream of PI3K and Rac1. To examine the functional role of phosphorylated ERM proteins, a dominant negative mutant form of moesin (T558A) was introduced into PC12 cells. The mutant significantly reduced the frequency of cells with neurites following NGF treatment. Our results indicate that PI3K, Rac1 and Akt-dependent phosphorylation of moesin is required for the NGF-induced neurite formation in differentiating PC12 cells. PMID- 20307616 TI - Opposite changes in cannabinoid CB1 and CB2 receptor expression in human gliomas. AB - Gliomas are the most important group of malignant primary brain tumors and one of the most aggressive forms of cancer. During the last years, several studies have demonstrated that cannabinoids induce apoptosis of glioma cells and inhibit angiogenesis of gliomas in vivo. As the effects of cannabinoids rely on CB(1) and CB(2) receptors activation, the aim of the present study was to investigate both receptors protein expression in cellular membrane homogenates of human glial tumors using specific antibodies raised against these proteins. Additionally, we studied the functionality of the cannabinoid receptors in glioblastomas by using WIN 55,212-2 stimulated [(35)S]GTPgammaS binding. Western blot analysis showed that CB(1) receptor immunoreactivity was significantly lower in glioblastoma multiforme (-43%, n=10; p<0.05) than in normal post-mortem brain tissue (n=16). No significant differences were found for astrocytoma (n=6) and meningioma (n=8) samples. Conversely, CB(2) receptor immunoreactivity was significantly greater in membranes of glioblastoma multiforme (765%, n=9; p<0.05) and astrocytoma (471%, n=4; p<0.05) than in control brain tissue (n=10). Finally, the maximal stimulation of [(35)S]GTPgammaS binding by WIN 55,212-2 was significantly lower in glioblastomas (134+/-4%) than in control membranes (183+/-2%; p<0.05). The basal [(35)S]GTPgammaS binding and the EC(50) values were not significantly different between both groups. The present results demonstrate opposite changes in CB(1) and CB(2) receptor protein expression in human gliomas. These changes may be of interest for further research about the therapeutic effects of cannabinoids in glial tumors. PMID- 20307617 TI - Association analysis of 3p21 with Crohn's disease in a New Zealand population. AB - Recent genome-wide association studies have provided evidence for the involvement of 3p21 in the pathogenesis of Crohn's disease (CD). Here we attempted to validate the 3p21 region in a well characterized CD case-control New Zealand dataset of 329 CD patients and 521 controls by genotyping tagging single nucleotide polymorphisms (SNPs) across this region. Analysis revealed significant differences between patients and controls for six of 14 SNPs: rs9874472, rs1800668, rs11716445, rs4283605, rs2131109, and rs6446298. Five of these demonstrated strong interaction with CARD15 and phenotypic analysis demonstrated association of these SNPs with age at first diagnosis, CD location, CD behavior and requirement of bowel resection. The results from this study support the accumulating evidence that suggests the 3p21 region is a CD-associated locus, although it remains unclear which is the causative SNP and/or gene. PMID- 20307618 TI - Description and molecular modeling of two novel HLA alleles: HLA-A*0343 and A*0345. AB - We report the identification of two novel human leucocyte antigen (HLA) in two Caucasian individuals. HLA-A*0343 differs from A*03010101 by four changes at nucleotides 411-414 (CCGG-->TGAA) and by a point mutation at position 418 (G- >C). These differences lead to two amino acid substitutions at codon 114, where arginine has changed into negatively charged glutamic acid, and at codon 116, where aspartic acid has changed into positively charged histidine. Molecular modeling showed that these changes have a profound influence on the overall charge of the F pocket of the groove, resulting in potentially important changes in the peptide repertoire. HLA-A*0345 was found in a hematological female patient candidate to bone marrow transplantation. This new variant differs from HLA A*03010101 at position 845 (C-->A) encoding an amino acid change of threonine to asparagine at codon 258 located in the alpha3 domain. Molecular modeling does not suggest a substantial role of this substitutions on the interaction with beta2 microglobulin or CD8. PMID- 20307619 TI - HF-rTMS treatment decreases psychomotor retardation in medication-resistant melancholic depression. AB - Repetitive Transcranial Magnetic Stimulation (rTMS) applied to the left dorsolateral prefrontal cortex (DLPFC) might be a promising treatment strategy for depression. As one of the key features of melancholic depression is disturbances in psychomotor activity, we wanted to evaluate whether HF-rTMS treatment could influence psychomotor symptoms. Twenty antidepressant-free unipolar melancholic depressed patients, all at least stage III medication resistant, were studied. All were treated with 10 sessions of High-Frequency (HF) rTMS applied to the left dorsolateral prefrontal cortex (DLPFC) under MRI guidance. Forty percent of the patients showed a reduction of at least 50% on their initial 17-item Hamilton Depression Rating Score (HDRS) scale and were defined as clinical responders. Regardless of clinical outcome HF-rTMS treatment resulted in significant decreases on the Depressive Retardation Rating Scale (DRRS) scores. Although this was an open study in a relatively small sample, our results suggest that HF-rTMS might act on the 'psychomotor' level and these findings could add some further information as to why this kind of treatment can be beneficial for severely depressed patients of the melancholic subtype. PMID- 20307620 TI - Imipramine on the treatment of chronic dizziness and panic disorder--3 cases report. PMID- 20307621 TI - Successful augmentation of clozapine-resistant treatment of schizophrenia with clonidine. PMID- 20307622 TI - Quetiapine XR: current status for the treatment of major depressive disorder. AB - Quetiapine fumarate extended release (XR) has been approved for treatment of schizophrenia and bipolar disorder. Quetiapine may have antidepressant effects through effects on 5-HT(2A) receptor, 5-HT(1A) receptor, dopamine receptor, glutamate receptor and norepinephrine transporter. Recently, 7 large-scale randomized, double-blind, placebo (2-studies with active comparator)-controlled clinical trials have demonstrated that quetiapine XR has clinically meaningful efficacy as monotherapy and adjunct therapy to antidepressants for the treatment of adult patients with major depressive disorder (MDD). In such clinical trials, quetiapine XR was generally well tolerated, although weight gain and changes in metabolic parameters, consistent with the known profile of quetiapine, were observed in some patients. As of December 2009, the United States Food and Drug Administration has approved quetiapine XR for the adjunct treatment of MDD. From the data of currently available clinical trials, this review provides an overview of the data and clinical implications for quetiapine XR in the treatment of MDD to enhance clinicians understanding of the use of quetiapine XR in the treatment of MDD. PMID- 20307623 TI - Exposure of human skin to benzo[a]pyrene: role of CYP1A1 and aryl hydrocarbon receptor in oxidative stress generation. AB - Exposure to benzo[a]pyrene (BaP) can induce inflammatory skin diseases and skin cancer, which are both associated to oxidative stress. BaP is known to bind with high specificity to the aryl hydrocarbon receptor (AhR), modifying the expression of CYP1A1, involved both in cancer and inflammation. While the current knowledge is based on murine skin and cell culture data, in this study human healthy skin has been treated with 5muM BaP in conditions simulating occupational and environmental exposure. AhR and CYP1A1 expression was evaluated by Western blotting, which revealed their presence even in control untreated skin; both enzyme and receptor increased more than twofold after exposure to BaP. AhR expression level was lower than CYP1A1 in basal conditions and following induction. Oxidative stress was evaluated in terms of MTT reduction, protein peroxidation and reactive oxygen species (ROS) formation. A significant increase in ROS and carbonyl compound production, as well as reduced tissue viability have been determined by BaP. The results of this experiment indicate that BaP, an AhR agonist, can significantly increase receptor and CYP1A1 expression and induce oxidative stress in human skin, confirming the involvement of this pathway in the pathogenesis of tissue damage due to polycyclic aromatic hydrocarbons. PMID- 20307624 TI - Clinical study investigating abrasive effects of three toothpastes and water in an in situ model. AB - OBJECTIVES: This in situ study compared the abrasive effect of repeated brushings (over 10 days) of a low relative abrasive dentine (RDA) toothpaste with moderate and high relative abrasive dentine (RDA) toothpastes, on human dentine in situ. MATERIALS AND METHODS: The study design was single centre, single blind, randomized, split mouth, two period, four-treatment cross-over, in situ study in 20 healthy subjects. Subjects wore bi-lateral lower buccal appliances each fitted with four dentine sections with treatment applied with a power toothbrush, during each 10 day study period. Samples were measured at baseline, day 5 and day 10 by contact profilometry, and baseline and day 10 with non-contact profilometry. RESULTS: Nineteen subjects were included in the efficacy analysis. Results as measured by contact and non-contact profilometry from brushing with the moderate RDA paste and high RDA paste showed significantly (p<0.0001) more abrasion to dentine than brushing with the low RDA paste or water after 10 days. Dentine loss following tooth brushing with the low RDA paste was not significantly different from brushing with water, after 10 days. CONCLUSIONS: The methodology successfully showed clear differentiation between the amount of dentine lost following toothbrushing with the low RDA paste compared to the moderate or high RDA pastes. Dentine loss following brushing with the low RDA paste showed a comparable degree of abrasion to brushing with water. PMID- 20307625 TI - Valproic acid stimulates clusterin expression in human astrocytes: Implications for Alzheimer's disease. AB - Clusterin is a secreted molecular chaperone, also called apolipoprotein J. Recent genetic studies have demonstrated that clusterin is a significant susceptibility gene for late-onset Alzheimer's disease (AD). Clusterin shares several properties with apolipoprotein E, a well-known risk gene for AD, i.e. they bind to amyloid beta peptides and are present in neuritic plaques, enhance the clearance of amyloid-beta peptides in brain, and are included in lipid particles and thus regulate cholesterol traffic. Biochemical studies indicate that clusterin can prevent the progress of AD pathogenesis. We have observed earlier that histone deacetylase (HDAC) inhibitors can induce the expression of clusterin in several neuroblastoma and glioma cell lines. Recent studies have revealed that valproic acid, a common and well-tolerated drug for epilepsy and bipolar disorders, is a potent HDAC inhibitor. In this study, we examined whether valproic acid can induce the expression of clusterin in human astrocytes. Our results demonstrated that valproic acid is a potent inducer of clusterin expression and secretion in human astrocytes at the therapeutical concentrations. Another clinically used HDAC inhibitor, the cancer drug, Vorinostat (SAHA, suberoylanilide hydroxamic acid), also robustly stimulated the expression of clusterin in human astrocytes. One could postulate that valproic acid may be able to prevent amyloid-beta aggregation in AD, as observed in transgenic AD mice, by increasing clusterin expression. PMID- 20307626 TI - Effect of the bases flanking an abasic site on the recognition of nucleobase by amiloride. AB - BACKGROUND: We explain here the various non-covalent interactions which are responsible for the different binding modes of a small ligand with DNA. METHODS: The combination of experimental and theoretical methods was used. RESULTS: The interaction of amiloride with thymine was found to depend on the bases flanking the AP site and different binding modes were observed for different flanking bases. Molecular modeling, absorption studies and binding constant measurements support for the different binding patterns. The flanking base dependent recognition of AP site phosphates was investigated by (31)P NMR experiments. The thermodynamics of the ligand-nucleotide interaction was demonstrated by isothermal titration calorimetry. The emission behavior of amiloride was found to depend on the bases flanking the AP site. Amiloride photophysics in the context of AP-site containing DNA is investigated by time-dependent density functional theory. CONCLUSIONS: Flanking bases affect the ground and excited electronic states of amiloride when binding to AP site, which causes flanking base-dependent fluorescence signaling. GENERAL SIGNIFICANCE: The various noncovalent interactions have been well characterized for the determination of nucleic acid structure and dynamics, and protein-DNA interactions. However, these are not clear for the DNA-small molecule interactions and we believe that our studies will bring a new insight into such phenomena. PMID- 20307627 TI - The sedimentation properties of ferritins. New insights and analysis of methods of nanoparticle preparation. AB - BACKGROUND: Ferritin exhibits complex behavior in the ultracentrifuge due to variability in iron core size among molecules. A comprehensive study was undertaken to develop procedures for obtaining more uniform cores and assessing their homogeneity. METHODS: Analytical ultracentrifugation was used to measure the mineral core size distributions obtained by adding iron under high- and low flux conditions to horse spleen (apoHoSF) and human H-chain (apoHuHF) apoferritins. RESULTS: More uniform core sizes are obtained with the homopolymer human H-chain ferritin than with the heteropolymer horse spleen HoSF protein in which subpopulations of HoSF molecules with varying iron content are observed. A binomial probability distribution of H- and L-subunits among protein shells qualitatively accounts for the observed subpopulations. The addition of Fe(2+) to apoHuHF produces iron core particle size diameters from 3.8 + or - 0.3 to 6.2 + or - 0.3 nm. Diameters from 3.4 + or - 0.6 to 6.5 + or - 0.6 nm are obtained with natural HoSF after sucrose gradient fractionation. The change in the sedimentation coefficient as iron accumulates in ferritin suggests that the protein shell contracts approximately 10% to a more compact structure, a finding consistent with published electron micrographs. The physicochemical parameters for apoHoSF (15%/85% H/L subunits) are M=484,120 g/mol, nu=0.735 mL/g, s(20,w)=17.0 S and D(20,w)=3.21 x 10(-)(7) cm(2)/s; and for apoHuHF M=506,266 g/mol, nu=0.724 mL/g, s(20,w)=18.3S and D(20,w)=3.18 x 10(-)(7) cm(2)/s. SIGNIFICANCE: The methods presented here should prove useful in the synthesis of size controlled nanoparticles of other minerals. PMID- 20307628 TI - AFM observation of single, functioning ionotropic glutamate receptors reconstituted in lipid bilayers. AB - BACKGROUND: Ionotropic glutamate receptors (iGluRs) are responsible for extracellular signaling in the central nervous system. However, the relationship between the overall structure of the protein and its function has yet to be resolved. Atomic force microscopy (AFM) is an important technique that allows nano-scale imaging in liquid. In the present work we have succeeded in imaging by AFM of the external features of the most common iGluR, AMPA-R (alpha-amino-3 hydroxy-5-methyl-4-isoxazole propionic acid receptor), in a physiological environment. METHODS: Homomeric GluR3 receptors were over-expressed in insect cells, purified and reconstituted into lipid membranes. AFM images were obtained in a buffer from membranes immobilized on a mica substrate. RESULTS: Using Au nanoparticle-conjugated antibodies, we show that proteins reconstitute predominantly with the N-terminal domain uppermost on the membrane. A tetrameric receptor structure is clearly observed, but it displays considerable heterogeneity, and the dimensions differ considerably from cryo-electron microscopy measurements. CONCLUSIONS: Our results indicate that the extracellular domains of AMPA-R are highly flexible in a physiological environment. GENERAL SIGNIFICANCE: AFM allows us to observe the protein surface structure, suggesting the possibility of visualizing real time conformational changes of a functioning protein. This knowledge may be useful for neuroscience as well as in pharmaceutical applications. PMID- 20307629 TI - Ras signalling regulates differentiation and UCP1 expression in models of brown adipogenesis. AB - BACKGROUND: The Ras/Raf/MEK/ERK pathway has been recognised as an important signalling module in adipogenesis and adipocyte function, but whether it promotes or inhibits the formation of fat cells has not been reconciled. METHODS: Here we investigate the significance of Ras signalling intensity on two unrelated models of mouse brown adipocyte differentiation. RESULTS: A constitutively active H-Ras mutant (Ras V12) caused a complete block of adipose conversion, as manifested by a lack of both lipid accumulation and induction of adipocyte gene expression. The Ras V12-mediated impediment of differentiation was inefficiently rescued by forced expression of the adipogenic transcription factors C/EBPalpha and PPARgamma. However, the defective differentiation was alleviated by MEK inhibitors, suggesting that the obstruction of differentiation was dependent on activation of ERK. A dominant interfering H-Ras mutant (Ras N17) did not inhibit differentiation, but led to increased expression of genes important for energy dissipation in brown fat cells, including UCP1. GENERAL SIGNIFICANCE: These data suggest that the intensity of Ras signalling is important for differentiation and UCP1 expression in models of brown adipogenesis. PMID- 20307630 TI - Nepetalactone content in shoot cultures of three endemic Nepeta species and the evaluation of their antimicrobial activity. AB - Rapid micropropagation of Nepeta rtanjensis, N. sibirica and N. nervosa was performed. Qualitative and quantitative nepetalactone content in methanol extracts of in vitro grown plants was analysed by reverse-phase HPLC coupled with UV and MS detection. Only trans,cis-nepetalactone was detected in shoots of N. rtanjensis, while cis,trans-nepetalactone stereoisomer was present in N. sibirica. No nepetalactone was observed in shoots of N. nervosa. The antimicrobial activity of methanol extracts, against eight bacterial and eight fungal species, was evaluated. All the tested extracts showed significant antibacterial and strong antifungal activity. However, N. rtanjensis extract exhibited the best antimicrobial potential. PMID- 20307631 TI - Selective vulnerability of the striatal subregions of C57BL/6 mice to paraquat. AB - Paraquat (PQ) is a strong redox agent that contributes to the formation of reactive oxygen species (ROS) and induces toxicity of the nigrostriatal dopaminergic system. In this study, we investigated the effect of PQ on the dopaminergic system of four striatal subregions. Male C57BL/6 mice (aged 7 weeks and 23-25 g) were used for this study. The mice were administrated with normal saline or PQ (10mg/kg i.p.) twice weekly for three consecutive weeks, and we evaluated changes in body weight and the performance of motor coordination. We also measured changes in tyrosine hydroxylase (TH) immunoreactivity, dopamine (DA) and its metabolites, reduced glutathione (GSH), and oxidized glutathione (GSSG) in the striatum. The body weight gain of PQ-treated mice was lower than that of control mice 2 weeks after PQ administration, and this lowering effect was sustained until 4 weeks after PQ administration. In the rota-rod test, PQ had a significant effect on the time it took mice to fall from the rotating rod at 2 weeks after injection as compared to the control rats, and the effect was sustained up to 4 weeks after PQ administration. Additionally, the densities of TH-positive fibers were reduced in dorsal regions of both the striata and ventral subregion of the caudal striatum (RD, CD and CV subregions). The DA level however, decreased in four subregions of the striata. The rate of DA oxidation and O-methylation increased in the RD subregion. After PQ administration, GSH levels were significantly reduced in the RD and CV subregions, but GSSG levels in the RD and CD subregions increased compared to the control rats. The ratio of GSH/GSSG also decreased in the RD and CD subregions. We found that repeated PQ injection altered DA metabolism through the generation of oxidative stress in the striatum, and although the RD subregion showed the most prominent change, the dorsal region of the striatum may be more sensitive to PQ exposure. PMID- 20307632 TI - Direct toxicity effects of sulfo-conjugated troglitazone on human hepatocytes. AB - Troglitazone (TGZ), an orally active hypoglycemic agent, was found to be associated with severe drug-induced liver failure and was withdrawn from the market in 2000. Although the exact mechanism is not clear, it has been postulated that the formation of its major sulfo-conjugated metabolite (TGZS) plays an important role in its toxicity. TGZS inhibits bile salt export pump (BSEP) that causes accumulation of bile salts in liver. High concentration of bile salts causes cell death and mitochondrial dysfunction via detergent properties. One question arises whether TGZS has direct toxicity effect on human liver cells in addition to BSEP inhibition. In this study, both TGZ and chemically synthesized TGZS were incubated with normal human hepatocytes (THLE-2 cells) for measuring their cytotoxicity in vitro using the MTT assay. Glutathione (GSH) and protein carbonyl (PC) assays were further performed to measure the oxidative stress generated by these two compounds during incubation with THLE-2 cells. The results from this study indicated that TGZS (EC(50)=21.74+/-5.38 microM) was more toxic than TGZ (EC(50)=41.12+/-4.3 microM) in THLE-2 cells. The GSH and PC data further confirmed that TGZS produced greater oxidative stress in THLE-2 cells as compared to TGZ. In conclusion, our study demonstrated for the first time that TGZS has direct toxicity effect on human liver cells and may be partially responsible for the hepatotoxicity of TGZ. PMID- 20307633 TI - The coefficient of rolling resistance (CoRR) of some pharmaceutical tablets. AB - Experiments have been conducted to measure the coefficient of rolling resistance (CoRR) of some pharmaceutical tablets and several common materials, such as glass beads and steel ball bearings. CoRR values are required as inputs for discrete element method (DEM) models which can be used to model particulate flows and solid dosage form manufacturing processes. Until now there have been no CoRR data reported for pharmaceutical materials, and thus these new data will help to facilitate more accurate modeling of pharmaceutical systems. PMID- 20307634 TI - Improvement of dissolution and absorption properties of poorly water-soluble drug by preparing spray-dried powders with alpha-glucosyl hesperidin. AB - The feasibility of alpha-glucosyl hesperidin (Hsp-G) to improve the dissolution and bioavailability of poorly water-soluble drug was investigated. A spray-dried powder (SDP) of Hsp-G and flurbiprofen (FP), an acidic drug (pK(a)=3.78) with low water solubility, was prepared by a spray-drying method. Powder X-ray diffraction analysis revealed the conversion of FP from the crystal to the amorphous form when dispersed in Hsp-G. The SDPs of FP/Hsp-G resulted in pronounced improvement in both the dissolution rate and solubility of FP. The apparent solubility of FP in hydrochloric acid solution (pH 1.2) was improved by 10-fold more than untreated FP crystals when prepared as SDPs in Hsp-G. The bioavailability of FP from the prepared SDPs was evaluated in vivo after oral administration to rats, in comparison with the untreated FP crystals. The results revealed 2.5- and 2.8 fold improvement in the C(max) and AUC values, respectively, after oral administration of the SDPs of FP/Hsp-G. In conclusion, Hsp-G is a potentially safe material to enhance the dissolution and absorption of poorly water-soluble drugs. PMID- 20307635 TI - Biochemical and biophysical characterization of lysozyme modified by PEGylation. AB - PEGylation is a strategy that has been used to improve the biochemical properties of proteins and their physical and thermal stabilities. In this study, hen egg white lysozyme (EC 3.2.1.17; LZ) was modified with methoxypolyethylene glycol-p nitrophenyl carbonate (mPEG-pNP, MW 5000). This PEGylation of LZ produced conjugates that retained full enzyme activity with glycol chitosan, independent of degree of enzyme modification; its biological activity with the substrate Micrococcus lysodeikticus was altered according to its degree of modification. The conjugate obtained with a low degree of mPEG-pNP/NH(2) modification was studied by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF), demonstrating a spectral peak at m/z 19,988 Da with 77% of its original enzymatic activity. Spectroscopic studies of Fourier transform infrared (FTIR) and circular dichroism (CD) did not show any relevant differences in protein structure between the native and conjugate LZ. Studies of the effects of pH and temperature on PEGylated LZ indicated that the conjugate was active over a broad pH range, stable at 50 degrees C, and demonstrated resistance to proteolytic degradation. PMID- 20307636 TI - Distribution of perineuronal nets in the human superior olivary complex. AB - Perineuronal nets (PNNs) are specialized assemblies of chondroitin sulfate proteoglycans (CSPGs) in the central nervous system that form a lattice-like covering over the cell body, primary dendrites and initial axon segment of select neuronal populations. PNNs appear to play significant roles in development of the central nervous system, neuronal protection, synaptic plasticity and local ion homeostasis. In seven human brainstems (average age=81 years), we have utilized Wisteria floribunda (WFA) histochemistry and immunocytochemistry for CSPG to map the distribution of PNNs within the nuclei of the human superior olivary complex (SOC). Within the SOC, the majority of net-bearing neurons are situated in the most medially situated nuclei, especially the superior paraolivary nucleus and medial nucleus of the trapezoid body. Net-bearing neurons are consistently found in the ventral nucleus of the trapezoid body and posterior periolivary nucleus, but to a lesser extent in the lateral nucleus of the trapezoid body. Finally, perineuronal nets are typically absent from the lateral and medial superior olives. PMID- 20307637 TI - Chemopreventive and anti-cancer properties of the aqueous extract of flowers of Butea monosperma. AB - ETHNOPHARMACOLOGICAL RELEVANCE: Butea monosperma (Lam.) (Fabaceae) popularly known as 'flame of the forest' has been widely used in the traditional Indian medical system of 'Ayurveda' for the treatment of a variety of ailments including liver disorders. AIM OF THE STUDY: To evaluate the antioxidative, anti inflammatory, hepatoprotective and anti-cancer activities of the aqueous extract of Butea monosperma flowers. MATERIALS AND METHODS: Dried flowers of Butea monosperma were extracted with water. The extract was tested for its anti proliferative, pro-apoptotic and anti-carcinogenic effects in hepatoma cell lines. The chemopreventive and anti-angiogenic effects of the extract were evaluated by its daily oral administration in a HBV-related X15-myc mouse model of hepatocellular carcinoma (HCC). RESULTS: Treatment with the aqueous extract inhibited cell proliferation and accumulation of cells in G1 phase. This was accompanied by a marked reduction in the levels of activated Erk1/2 and SAPK/JNK and induction of apoptotic cell death. Oral administration of the extract in transgenic mice conferred hepatoprotection as is evident from normal serum ALT levels and improved liver histopathology and lowered serum VEGF level. CONCLUSIONS: The ability of aqueous extract of Butea monosperma flowers to impose growth arrest and trigger pro-apoptotic death in cell culture strongly correlated with its strong chemopreventive effect in vivo when given orally. PMID- 20307638 TI - Effect of an extract of Andrographis paniculata leaves on inflammatory and allergic mediators in vitro. AB - AIM OF STUDY: Andrographis paniculata has been known to possess widespread traditional application in the treatment of allergy and inflammatory diseases. In the current study, we sought to examine the effects of an extract of Andrographis paniculata leaves on inhibition of lipopolysaccharide (LPS) induced [nitric oxide (NO), prostaglandin E(2) (PGE(2)), interleukin-1beta (IL-1 beta), and interleukin 6 (IL-6)] and calcimycin (A23187) induced [leukotriene B(4) (LTB(4)), thromboxane B(2) (TXB(2)) and histamine] mediators in diverse cell based models. MATERIALS AND METHODS: Effect of an extract of Andrographis paniculata leaves (AP) was studied on inhibition of LPS induced NO, PGE(2), IL-1 beta and IL-6 in J774A.1 murine macrophages; A23187 induced LTB(4) and TXB(2) in HL-60 promyelocytic leukemic cells and histamine in RBL-2H3 rat basophilic leukemia cells. RESULTS AND CONCLUSION: AP illustrated significant alleviation of pro-inflammatory, inflammatory, and allergic mediators. However, no inhibition was observed against histamine release. This outcome has been summed up to deduce that AP is fairly potent in attenuating the inflammation by inhibiting pro-inflammatory (NO, IL-1 beta and IL-6), inflammatory (PGE(2) and TXB(2)) and allergic (LTB(4)) mediators. PMID- 20307639 TI - Sedative and anticonvulsant activities of methanol extract of Dorstenia arifolia in mice. AB - ETHNOPHARMACOLOGICAL RELEVANCE: Dorstenia arifolia is a plant that has been used in the folk medicine to produce hypnotic, sedative and ansiolitic effects but the pharmacological properties have not yet been studied. In addition, the smoke of its rhizome is reputed to induce lethargic sensation. AIMS OF THE STUDY: The present study investigated possible activities of the methanol extract (ME) of Dorstenia arifolia rhizome on the central nervous system (CNS). MATERIALS AND METHODS: ME was tested for sedative, hypnotic and anticonsulsant effects using locomotor activity evaluation, pentobarbital-induced sleeping time and pentylenetetrazol (PTZ)-induced convulsion, respectively. RESULTS: Intraperitoneal administration of ME (10 and 50mg/kg) significantly decreased locomotor activity from 205.2+/-25.6 movements/min (DMSO) to 112.1+/-18.4 (P<0.05) and 114.9+/-16.9 (P<0.05), respectively. Flumazenil (10 mg/kg), an antagonist of GABA(A) receptor, prevented the ME-induced sedation. Treatment with ME (50mg/kg) significantly increased the duration of pentobarbital-induced sleeping time from 41.0+/-2.3 to 57.9+/-2.9 min (P<0.05). The latencies to seizures after intraperitoneal injection of PTZ was recorded and compared between groups. ME promoted a significant protection of PTZ-induced seizures and mortality in a dose-dependent manner. CONCLUSIONS: Our findings indicate that ME of Dorstenia arifolia rizhome has pronounced central effects, and that the sedative and anticonvulsant activities may be related to a facilitation of the GABAergic transmission. PMID- 20307640 TI - Correlation between synergistic action of Radix Angelica dahurica extracts on analgesic effects of Corydalis alkaloid and plasma concentration of dl-THP. AB - AIM OF STUDY: Yuanhu Zhitong prescription that consists of Corydalis yanhusuo and Radix Angelicae dahuricae has been used for the treatment of gastralgia, costalgia, headache and dysmenorrhea in Traditional Chinese Medicine. Our previous studies demonstrated that Corydalis alkaloid (CA, derived from the root of Corydalis yanhusu) had potent analgesic properties, and the total coumarins of Angelica dahurica (Cou) and volatile oil (VO) that derived from the root of Radix Angelicae dahuricae all could increase the analgesic effect of CA. The major objective of this paper was to investigate the mechanism that leading the analgesia of CA increased by Cou and (or) VO. MATERIALS AND METHODS: The relationship between analgesic effect of CA and the plasma concentration of Dl tetrahydropalmatine (dl-THP, active component of CA) was assayed in mice writhing test. The CA (34, 68 and 134 mg/kg) reduced the nociception by acetic acid intraperitoneal injection in a dose-dependent manner, and there was a significant linear relationship between the analgesic effect of CA and the plasma concentration of dl-THP. Then the plasma concentration of dl-THP at different time intervals in rats after oral administration of CA, CA-Cou, CA-VO and CA-Cou VO were examined by using HPLC. RESULTS AND CONCLUSION: The results indicated that Cou and (or) VO raised the plasma concentration of dl-THP prominently. In conclusion, the reason that Radix Angelica dahurica extracts reinforced the analgesic effects of Corydalis alkaloid was related to the improvement of the plasma concentration of dl-THP. PMID- 20307641 TI - Evaluation of anticancer activity of Cleome gynandra on Ehrlich's Ascites Carcinoma treated mice. AB - ETHNOPHARMACOLOGICAL RELEVANCE: The plant Cleome gynandra L. (Capparidaceae), is commonly known as 'Hurhur'and 'Karaila' in India and 'Cat's whiskers' in English. Traditionally the whole plant is used in the treatment of tumor, anti inflammatory and lysosomal stability actions. AIM OF STUDY: The objective of present study is to explore the anticancer activity of the methanol extract of the Cleome gynandra in Swiss albino mice against Ehrlich Ascites Carcinoma (EAC) cell line. MATERIALS AND METHODS: Anticancer activity of methanol extract of Cleome gynandra (MECG) was evaluated in Swiss albino mice against Ehrlich Ascites Carcinoma (EAC) cell line at the doses of 200 and 400mg/kg body weight intraperitoneally. MECG was administered for nine consecutive days. Twenty-four hours of last dose and 18 h of fasting, the mice were sacrificed and antitumor effect of MECG assessed by evaluating tumor volume, viable and nonviable tumor cell count, tumor weight and hematological parameters of EAC bearing host. RESULTS: MECG showed significant decrease in (p<0.01) tumor volume, viable cell count, tumor weight and elevated the life span of EAC tumor bearing mice. Hematological profile such as RBC, hemoglobin, WBC and lymphocyte count reverted to normal level in MECG treated mice. CONCLUSION: From the result it was showed that the extract has potent dose dependent anticancer activity and that is comparable to that of 5-fluorouracil. PMID- 20307642 TI - Nitric oxide in fruit ripening: trends and opportunities. AB - Monitoring ethylene is crucial in regulating post-harvest life of fruits. The concept of nitric oxide (NO) involvement in antagonizing ethylene is new. NO mediated physiologies casted through regulation of plant hormones are widely reported during developmental and stress chemistry having no direct link with ripening. Research in NO biology and understanding its interplay with other signal molecules in ripening fruits suggest ways of achieving greater synergies with NO applications. Experiments focused at convincingly demonstrating the involvement of NO in altering ripening-related ethylene profile of fruits, would help develop new processes for shelf life extension. This issue being the central theme of this review, the putative mechanisms of NO intricacies with other primary and secondary signals are hypothesized. The advantage of eliciting NO endogenously may open up various biotechnological opportunities for its precise delivery into the target tissues. PMID- 20307643 TI - d-Serine administration provokes lipid oxidation and decreases the antioxidant defenses in rat striatum. AB - The present work investigated the effects of intrastriatal administration of d serine on relevant parameters of oxidative stress in striatum of young rats. d Serine significantly induced lipid peroxidation, reflected by the significant increase of thiobarbituric acid-reactive substances, and significantly diminished the striatum antioxidant defenses, as verified by a decrease of the levels of reduced glutathione and total antioxidant status. Finally, d-serine inhibited superoxide dismutase activity, without altering the activities of glutathione peroxidase and catalase. In contrast, this d-amino acid did not alter sulfhydryl oxidation, a measure of protein oxidative damage. The present data indicate that d-serine in vivo administration induces lipid oxidative damage and decreases the antioxidant defenses in the striatum of young rats. Therefore, it is presumed that this oxidative stress may be a pathomechanism involved at least in part in the neurological damage found in patients affected by disorders in which d-serine metabolism is compromised, leading to altered concentrations of this d-amino acid. PMID- 20307644 TI - Regulation of hemagglutinin/protease expression by the VarS/VarA-CsrA/B/C/D system in Vibrio cholerae. AB - In this study, through the analysis of Vibrio cholerae 2740-80 mutant strains produced by the cholera toxin subunit B gene containing Mariner-based transposon, we found that disruption of the varS gene, a member of the recently reported sensory system VarS/VarA-CsrA/B/C/D, resulted in altered expression of hemagglutinin/protease A. To further investigate the connection between VarS and HapA, we generated an additional varS mutant, V. cholerae 2740-80-VS, and examined the effect of this mutation on expression of HapA and of genes in the VarS/VarA-CsrA/B/C/D system. 2740-80-VS showed decreased expression of varS, csrB/C, hapR, and hapA along with increased biofilm production. Interestingly, expression of the alternative sigma factor sigma(s), which is important for adaptation to environmental stress, was also decreased in this mutant. These results indicate that the VarS/VarA-CsrA/B/C/D system is involved in the control of HapA expression and biofilm production in V. cholerae 2740-80 through HapR regulation, and also that VarS/VarA controls expression of sigma(s) for HapA regulation. PMID- 20307645 TI - Identification of a novel angiogenin inhibitor 1 and its association with hyaluronidase of Streptococcus suis serotype 2. AB - To characterize the role of hyaluronidase (Hyl) of Streptococcus suis serotype 2 (S. suis 2), the hylA gene that encodes Hyl was cloned, expressed and purified. A murine brain cDNA library was used to screen for interacting proteins of Hyl. Employing the yeast two-hybrid system, a novel murine ribonuclease, angiogenin inhibitor 1 (AI1), which shares 93% homology with porcine AI1, was shown to interact with Hyl in yeast. Through co-immunoprecipitation assays, the interaction between AI1 and Hyl was further confirmed. Transcription and translation products of the identified cDNA were detected in both normal cells and S. suis 2-infected cells. AI1 was found to localize mainly in the cytoplasm of 293T cells. These results suggested that the identified protein AI1 might be involved in the pathogenesis of meningitis through interaction with Hyl of S. suis 2. PMID- 20307646 TI - Comparison of immunotoxic effects induced by the extracts from methanol and gasoline engine exhausts in vitro. AB - Gasoline engine exhaust has been considered as a major source of air pollution in China. Due to lower cyto- and geno-toxicity effects of methanol engine exhaust, methanol is regarded as a potential substitute for gasoline. We have previously compared cyto- and geno-toxicities of gasoline engine exhaust with that of methanol engine exhaust in A549 cells (Zhang et al., 2007).To characterize the immunotoxic effects for gasoline and methanol engine exhausts in immune cell, in this study, we further compared effects of gasoline and methanol engine exhausts on immune function in RAW264.7 cell and rabbit alveolar macrophages. Results showed that both gasoline and methanol engine exhaust could evidently inhibit RAW264.7 cell proliferation, promote RAW264.7 cell apoptosis, decrease E-rosette formation rate and inhibit anti-tumor effects of alveolar macrophages, at the same time, these effects of gasoline engine exhaust were far stronger than those of methanol engine exhaust. In addition, gasoline engine exhaust could significantly inhibit activities of ADCC of alveolar macrophages, but methanol engine exhaust could not. These results suggested that both gasoline and methanol engine exhausts might be immunotoxic atmospheric pollutants, but some effects of gasoline engine exhaust on immunotoxicities may be far stronger than that of methanol engine exhaust. PMID- 20307647 TI - Cyclobutane pyrimidine dimers are photosensitised by carprofen plus UVA in human HaCaT cells. AB - Every year in the UK about 75,000 cases of non-melanoma skin cancer (NMSC) are registered, and about 9500 people are diagnosed with cutaneous melanoma (CM). The main risk factor for these cancers is exposure to sunlight. The effects of light on skin are wavelength dependent, with wavelengths in the UVB waveband (280-315 nm) being the most carcinogenic. UVB is directly absorbed by DNA, producing dimeric pyrimidine photoproducts including cyclobutane pyrimidine dimers (CPD) and pyrimidine (6-4) pyrimodone photoproducts (6-4PP). However UVA (315-400 nm) can also produce CPD, induce skin tumours in mice, and has been shown to be mutagenic in cell culture. Although the precise role of UVA in human skin cancer remains to be elucidated, it comprises the major portion of solar UV radiation, transmits through window glass and can be delivered in high doses from tanning lamps. Non-steroidal anti-inflammatory drugs (NSAIDs), in particular the 2-aryl propionic acid derivatives, are a well-documented group of photosensitising chemicals producing clinical phototoxic and photoallergic reactions. We have used carprofen, a model compound from this group to see if it could amplify the effects of UVA and contribute to the formation of CPD by UVA. Preliminary work has shown that carprofen combined with low doses of UVA (lambda(max): 365 nm; 5 J/cm(2)) can produce both strand breaks (SB) and CPD in human skin or blood cells. CPD were detected indirectly by both an immunofluorescence method and as T4 endonuclease V sensitive sites in the comet assay. These findings show that compounds other than fluoroquinolones and psoralen derivatives may contribute to CPD formation in skin cells in combination with UVA. PMID- 20307648 TI - In utero exposure to di-(2-ethylhexyl) phthalate affects liver morphology and metabolism in post-natal CD-1 mice. AB - The plasticizer di-(2-ethylhexyl)phthalate (DEHP) affects reproductive development, glycogen and lipid metabolism. Whereas liver is a main DEHP target in adult rodents, the potential impact on metabolic programming is unknown. Effects of in utero DEHP exposure on liver development were investigated upon treatment of pregnant CD-1 mice on gestational days (GD)11-19. F1 mice were examined at post-natal days 21 (weaning) and 35 (start of puberty): parameters included liver histopathological, immunocytochemical and alpha-fetoprotein (AFP) gene expression analyses. In utero DEHP exposure altered post-natal liver development in weanling mice causing significant, dose-related (i) increased hepatosteatosis, (ii) decreased glycogen storage, (iii) increased beta-catenin intracytoplasmic localization (females only). At puberty, significantly decreased glycogen storage was still present in males. A treatment-induced phenotype was identified with lack of glycogen accumulation and intracytoplasmic localization of beta-catenin which was associated with increased AFP gene expression. Our findings suggested that DEHP alters post-natal liver development delaying the programming of glycogen metabolism. PMID- 20307649 TI - Testis dysfunction by isoproterenol is mediated by upregulating endothelin receptor A, leptin and protein kinase Cvarepsilon and is attenuated by an endothelin receptor antagonist CPU0213. AB - This study has examined whether upregulation of endothelin receptor A, leptin and phosphorylated protein kinase Cvarepsilon contributes to stress-induced testicular damaged and its possible reversal by endothelial (ET) antagonism. Adult male Sprague-Dawley rats were randomly divided into control and isoproterenol (ISO 1mg/kg, subcutaneous (s.c.), 10 days) groups, and intervened with the ET receptor antagonist CPU0213 (20mg/kg, s.c.), on days 6-10. In ISO group, testicular succinate dehydrogenase, lactate dehydrogenase, acid phosphotase, and gamma-glutamyl transpeptidase, and serum testosterone decreased, whereas FSH increased, relative to control. The seminiferous tubules were damaged in association with testicular upregulation of protein abundance of leptin and pPKCvarepsilon, and mRNA and protein expression of leptin receptor (OBRb) and ET(A). CPU0213 was effective in ameliorating these abnormalities. Over-expression of ET(A) and leptin accounting for the testis dysfunction is likely to be mediated by pPKCvarepsilon in the ISO treated rats. The upregulated ET pathway appears to be critical in pathologies of the testis. PMID- 20307650 TI - N-acetyl-L-methionyl-L-Dopa-methyl ester as a dual acting drug that relieves L Dopa-induced oxidative toxicity. AB - Initiation and progression of Parkinson's disease seem to be linked to oxidative stress, closely related to decreased mitochondrial functions and ubiquitin proteasome system dysfunction. To date, L-Dopa is the most effective medication , although long-term treatment can enhance oxidative stress and accelerate the degenerative process of residual cells. Therefore the inhibition of oxidation of L-Dopa/dopamine and the inhibition of reactive oxygen species formation are important strategies for neuroprotective therapy. Recently, several dual acting drugs, in which L-Dopa/dopamine are covalently linked to antioxidant molecules, were shown to induce sustained delivery of both L-Dopa/dopamine in rat plasma and striatum, suggesting that these compounds might be proposed as useful agents against Parkinson's disease. Here, by analyzing GSH levels and heme oxygenase-1 expression, we investigated in primary mesencephalic neuron cultures and in newborn mice the effects of the treatment with Ac-Met-LD-OMe. Moreover, by using proteasome inhibitor-treated mice as Parkinson's disease animal model, we demonstrated the beneficial effects of the systemic administration of this novel codrug. PMID- 20307651 TI - Role of Pin1 in neointima formation: down-regulation of Nrf2-dependent heme oxygenase-1 expression by Pin1. AB - Abnormal proliferation of vascular smooth muscle cells (VSMCs) contributes to intima formation after stenting and balloon angioplasty. Pin1, a peptidyl prolyl isomerase recognizing phosphorylated Ser/Thr-Pro, isomerizes the peptide bond. Because Pin1 overexpression is associated with transformation and the uncontrolled cell growth of tumors, we hypothesized that Pin1 functions as a chronic stimulator of VSMC proliferation. Pin1-positive smooth muscle cells were seen in the neointimal region of the femoral artery after guidewire injury. Exposure of VSMCS to platelet-derived growth factor (PDGF) increased Pin1 expression in a concentration-dependent manner. Basal cell growth rate and cyclin D1 expression were enhanced in Pin1-overexpressing VSMCs (Pin1-VSMCs). Moreover, PDGF-induced production of reactive oxygen species (ROS) in Pin1-VSMCs was higher than in control VSMCs. In Pin1-VSMCs, heme oxygenase-1 (HO-1) induction in response to nitric oxide donor was suppressed compared to control VSMCs. Nuclear translocation of nuclear factor E2-related factor-2 (Nrf2) was also diminished in Pin1-VSMCs. In contrast, the activity of the inducible minimal antioxidant response element (ARE) was potentiated in Pin1-null mouse embryonic fibroblasts (MEFs), compared to Pin1-wild-type MEFs. Moreover, Nrf2 ubiquitination was stimulated by Pin1 overexpression. Intraperitoneal injection of juglone (a Pin1 inhibitor) for 3weeks (1mg/kg, two times a week) significantly suppressed neointimal formation induced by wire injury. In conclusion, Pin1 induction during neointimal formation may be associated with ROS-mediated VSMC proliferation via down-regulation of Nrf2/ARE-dependent HO-1 expression. Pin1 may be a novel therapeutic target for several vascular diseases including atherosclerosis and stenosis. PMID- 20307652 TI - Polychlorinated biphenyl induced ROS signaling delays the entry of quiescent human breast epithelial cells into the proliferative cycle. AB - Polychlorinated biphenyls (PCBs) are environmental chemical contaminants that can produce reactive oxygen species (ROS) by autoxidation of dihydroxy-PCBs and redox cycling. We investigate the hypothesis that PCB induced perturbations in ROS signaling regulate the entry of quiescent cells into the proliferative cycle. Quiescent MCF-10A human breast epithelial cells were incubated with 0-3 micromolar of 2-(4-chlorophenyl)benzo-1,4-quinone (4-Cl-BQ), 2, 2', 4, 4', 5, 5' hexachlorobiphenyl (PCB 153), and Aroclor 1254 for 4 days. Cells were replated at a lower density and analyzed for cell cycle phase distributions, ROS levels, MnSOD expression, and cyclin D1 protein levels. Quiescent cells incubated with 4 Cl-BQ showed the maximal delay in entering S phase. This delay was associated with a decrease in MnSOD activity, protein and mRNA levels, and an increase in cellular ROS levels. Results from the mRNA turnover assay showed that the 4-Cl-BQ treatment selectively enhanced the degradation of the 4.2kb MnSOD transcript, while the half-life of the 1.5 kb transcript did not change. Accumulation of cyclin D1 protein levels in replated cells was suppressed in cells treated with 4 Cl-BQ. Pretreatment of quiescent cells with polyethylene glycol-conjugated superoxide dismutase and catalase suppressed 4-Cl-BQ induced increase in ROS levels, which was consistent with an increase in cyclin D1 accumulation, and entry into S phase. These results showed 4-Cl-BQ induced perturbations in ROS signaling inhibit the entry of quiescent cells into S phase. PMID- 20307653 TI - Evidence that yeast frataxin is not an iron storage protein in vivo. AB - Yeast cells deficient in the yeast frataxin homolog (Yfh1p) accumulate iron in their mitochondria. Whether this iron is toxic, however, remains unclear. We showed that large excesses of iron in the growth medium did not inhibit growth and did not decrease cell viability. Increasing the ratio of mitochondrial iron to-Yfh1p by decreasing the steady-state level of Yfh1p to less than 100 molecules per cell had very few deleterious effects on cell physiology, even though the mitochondrial iron concentration greatly exceeded the iron-binding capacity of Yfh1p in these conditions. Mossbauer spectroscopy and FPLC analyses of whole mitochondria or of isolated mitochondrial matrices showed that the chemical and biochemical forms of the accumulated iron in mitochondria of mutant yeast strains (Deltayfh1, Deltaggc1 and Deltassq1) displayed a nearly identical distribution. This was also the case for Deltaggc1 cells, in which Yfh1p was overproduced. In these mitochondria, most of the iron was insoluble, and the ratio of soluble-to insoluble iron did not change when the amount of Yfh1p was increased up to 4500 molecules per cell. Our results do not privilege the hypothesis of Yfh1p being an iron storage protein in vivo. PMID- 20307654 TI - Determination of permeation resistance distribution in in vitro cell monolayer permeation experiments. AB - The results of cell monolayer permeation experiments are often affected by concentration dependent cellular processes, such as active transport and metabolism. The rigorous analysis of the concentration dependence of these processes is often limited by the lack of knowledge of the actual concentration at the site of action because the measurement of the local concentration is seldom feasible. However, the local concentrations can be estimated if the rates into and out of a particular location are known. Thus, an insight into the distribution of the permeation resistance in the in vitro cell monolayer permeation experiments would enable the estimation of local concentrations during the permeation experiments and, consequently, a more thorough analysis of the concentration dependent processes involved in the transepithelial transfer of compounds. In this study, a compartmental model was constructed applicable for dissecting the roles of apical and basal side aqueous boundary layers and the cell membranes in the total permeation barrier for weakly acidic and basic compounds. The model was applied for the analysis of the Caco-2 permeation data of three high permeability compounds, propranolol, metoprolol and ibuprofen. Furthermore, the effects of extracellular pH and the agitation conditions on the local concentrations of these compounds were evaluated. PMID- 20307655 TI - Prediction of food effect by bile micelles on oral drug absorption considering free fraction in intestinal fluid. AB - The purpose of the present study was to derive a theoretical framework for prediction of the food effects by interactions with bile micelles on oral drug absorption. The effect of bile micelles was discussed based on the categories of permeability limited (PL), dissolution rate limited (DRL) and solubility limited (SL) absorption. SL was further categorized as the solubility-epithelial membrane limited (SL-E) and the solubility-unstirred water layer (UWL) limited (SL-U). In PL, an increase of bile micelles in the fed state was suggested to result in a negative food effect if the drug molecules bind to bile micelles because of a decrease of free monomer concentration. In DRL, a positive food effect was anticipated. In SL-E (e.g., pranlukast), little or no food effect was anticipated since the increase of apparent solubility (bile micelle bound molecule+free molecule) would be cancelled out by the decrease of effective permeability (the free monomer concentration at the epithelial membrane surface would remain the same. Total flux=solubilityxpermeability). In SL-U (e.g., danazol), a positive food effect was anticipated since the bile micelle bound molecules can permeate the UWL (however, slower than free monomer molecules). Based on this discussion, it was suggested that a formulation which could increase the free fraction at the epithelial membrane surface would be required to enhance oral absorption for SL-E (e.g., supersaturable formulations), whereas any formulation which can increase the UWL flux would be effective for SL-U (e.g., micro- to nano-emulsion systems, nano-milling and cyclodextrins). It was also suggested that a simple dissolution test would be misleading for SL-E and a simultaneous assessment of dissolution and permeation would be required. PMID- 20307656 TI - Effect of route of administration on the pharmacokinetics and toxicokinetics of cinnarizine in dogs. AB - AIMS: Cinnarizine, a piperazine derivative, is currently used for the treatment of cerebral thrombosis, cerebral arteriosclerosis, subarachnoid hemorrhage and some other diseases. However, it exhibits variable dissolution and low bioavailability after oral administration. Cinnarizine for injection was developed in order to enhance its bioavailability and make the practice more convenient for patients suffering from dysphagia. The aim of the present study was to compare the pharmacokinetics and toxicokinetics of cinnarizine following intravenous and oral administration in dogs and provide scientific basis for the development of cinnarizine for injection. METHODS: Beagle dogs were given single- or multiple-dose of cinnarizine by oral (single-dose: 10mg/kg; multiple-dose: 21.5, 12.9, 4.3mg/kg) and intravenous (single-dose: 10mg/kg; multiple-dose: 10, 6, 2mg/kg) routes. HPLC was applied to detect the plasma concentration of cinnarizine. The pharmacokinetics and toxicokinetics parameters were calculated and compared. RESULTS: The pharmacokinetics of cinnarizine following oral administration in dogs was found to fit the one-compartment mode. That of cinnarizine following intravenous injection in dogs was found to fit the two compartment model. The relative bioavailability of oral administration was 46.4%. Cinnarizine cumulated significantly in dogs when 10mg/kg cinnarizine was injected repeatedly. Multiple-dose of cinnarizine over 6mg/kg induced reversible kidney injury in dogs. CONCLUSION: The present study indicates that pharmacokinetics and toxicokinetics properties of cinnarizine for injection show advantages over the oral preparation. But caution should be taken with the cumulative action when cinnarizine is injected and the dose of cinnarizine should be lower than 6mg/kg. PMID- 20307657 TI - Pharmacokinetics of fexofenadine: evaluation of a microdose and assessment of absolute oral bioavailability. AB - A human pharmacokinetic study was performed to assess the ability of a microdose to predict the pharmacokinetics of a therapeutic dose of fexofenadine and to determine its absolute oral bioavailability. Fexofenadine was chosen to represent an unmetabolized transporter substrate (P-gP and OATP). Fexofenadine was administered to 6 healthy male volunteers in a three way cross-over design. A microdose (100microg) of (14)C-drug was administered orally (period 1) and intravenously by 30min infusion (period 2). In period 3 an intravenous tracer dose (100microg) of (14)C-drug was administered simultaneously with an oral unlabelled therapeutic dose (120mg). Plasma was collected from all 3 periods and analysed for both total (14)C content and parent drug by accelerator mass spectrometry (AMS). For period 3, plasma samples were also analysed using HPLC fluorescence to determine total drug concentration. Urine was collected and analysed for total (14)C. Good concordance between the microdose and therapeutic dose pharmacokinetics was observed. Microdose: CL 13L/h, CL(R) 4.1L/h, V(ss) 54L, t(1/2) 16h; therapeutic dose: CL 16L/h, CL(R) 6.2L/h, V(ss) 64L, t(1/2) 12h. The absolute oral bioavailability of fexofenadine was 0.35 (microdose 0.41, therapeutic dose 0.30). Despite a 1200-fold difference in dose of fexofenadine, the microdose predicted well the pharmacokinetic parameters following a therapeutic dose for this transporter dependent compound. PMID- 20307658 TI - Inhibition of oligopeptide transporter suppress growth of human pancreatic cancer cells. AB - Oligopeptide transporters are abundantly expressed in various types of cancer cells. We here synthesized two novel dipeptides, l-phenylalanyl sarcosine (Phe Sar) and 4-(4-methoxyphenyl)-l-phenylalanyl sarcosine (Bip(OMe)-Sar), and examined their effect on the growth of human pancreatic cancer AsPC-1 cells, which are known to highly express oligopeptide transporter PEPT1/SLC15A1. Growth of AsPC-1 cells was inhibited by these two peptides and a typical PEPT1/SLC15A1 substrate Gly-Sar. Growth inhibition by Gly-Sar, Phe-Sar and Bip(OMe)-Sar was concentration-dependent with half-maximal inhibitory concentration of 50, 0.91 and 0.55mM, respectively. These peptides also inhibited PEPT1-mediated [(3)H]Gly Sar uptake with half-maximal inhibitory concentration of 2.6, 0.81 and 0.27mM, respectively. Thus, the rank order of the tumor cell growth inhibition by these three peptides was the same as that of PEPT1-inhibitory activity. Growth of AsPC 1 cells was also inhibited by 2-aminobicyclo(2,2,1)heptane-2-carboxylic acid (BCH), which is a typical inhibitor of amino acid transporter system L. The growth inhibition by BCH and Gly-Sar was additive, suggesting that these compounds act at distinct loci. Oligopeptide transporters thus appear to be a promising target for inhibition of pancreatic cancer progression. These results also proposed the idea that oligopeptide transporter is required for growth of AsPC-1 cells. PMID- 20307659 TI - Development of a fluorescence-based assay for drug interactions with human Multidrug Resistance Related Protein (MRP2; ABCC2) in MDCKII-MRP2 membrane vesicles. AB - PURPOSE: To establish a fluorescence-based assay for drug interactions with the ABC-export-protein MRP2 (ABCC2). METHODS: Apical membrane vesicles were isolated by differential centrifugation from polarized MDCKII cells and MDCKII cells transfected with human MRP2. Vesicle fractions were characterized by electron microscopy, determination of the marker enzyme alkaline phosphatase and Western blot analysis of MRP2. Vesicle orientation was determined by measurement of 5' nucleotidase activity in the absence and in the presence of detergents. To assess MRP2 activity, the uptake of the fluorescent MRP2-substrate 5-(6)-carboxy-2',7' dichlorofluorescein (CDF) was determined in the absence and in the presence of other compounds potentially interacting with MRP2. RESULTS: Apical membrane vesicles could be isolated from cells in considerable purity as indicated by electron microscopy, enrichment of alkaline phosphatase and high enrichment of MRP2 in vesicles of MDCKII-MRP2 cells. About half of the vesicles showed "inside out" orientation. CDF was taken up into the membrane vesicles in a time- and concentration-dependent manner following a Michaelis-Menten type of kinetics with a K(M) of 39 microM and a V(max) of 465.3 fmol/(mgprotein x min). Thereby, uptake into vesicles from transfected cells was significantly higher than uptake into vesicles from control cells. Presence of known MRP2-substrates/inhibitors in the incubation medium decreased CDF uptake into the vesicles in a concentration dependent manner, whereas nonsubstrates/inhibitors had no effect. CONCLUSIONS: This CDF-based uptake assay can be used as a rapid and sensitive screening system to assess drug interactions with human MRP2 and therefore represents a useful tool in compound profiling. PMID- 20307660 TI - Loss of collagen-receptor DDR1 delays renal fibrosis in hereditary type IV collagen disease. AB - Alport syndrome is a hereditary type IV collagen disease leading to progressive renal fibrosis, hearing loss and ocular changes. End stage renal failure usually develops during adolescence. COL4A3-/- mice serve as an animal model for progressive renal scarring in Alport syndrome. The present study evaluates the role of Discoidin Domain Receptor 1 (DDR1) in cell-matrix interaction involved in pathogenesis of Alport syndrome including renal inflammation and fibrosis. DDR1/COL4A3 Double-knockouts were compared to COL4A3-/- mice with 50% or 100% expression of DDR1, wildtype controls and to DDR1-/- COL4A3+/+ controls for over 6years. Double-knockouts lived 47% longer, mice with 50% DDR1 lived 29% longer and showed improved renal function (reduction in proteinuria and blood urea nitrogen) compared to animals with 100% DDR1 expression. Loss of DDR1 reduced proinflammatory, profibrotic cells via signaling of TGFbeta, CTGF, NFkappaB and IL-6 and decreased deposition of extracellular matrix. Immunogold-staining and in situ hybridisation identified podocytes as major players in DDR1-mediated fibrosis and inflammation within the kidney. In summary, glomerular epithelial cells (podocytes) express DDR1. Loss of DDR1-expression in the kidney delayed renal fibrosis and inflammation in hereditary type IV collagen disease. This supports our hypothesis that podocyte-matrix interaction via collagen receptors plays an important part in progression of renal fibrosis in Alport disease. The blockade of collagen-receptor DDR1 might serve as an important new therapeutic concept in progressive fibrotic and inflammatory diseases in the future. PMID- 20307661 TI - Association between polymorphic variation in VDR and RXRA and circulating levels of vitamin D metabolites. AB - The vitamin D metabolite 1,25(OH)2D is the bioactive ligand of the vitamin D receptor (VDR). VDR forms a heterodimer with the retinoid X receptors (RXRs) that when bound to ligand influences the transcriptional control of genes that regulate circulating levels of vitamin D metabolites. Whether genetic variation in VDR or RXRA affects circulating levels of 1,25(OH)2D or 25(OH)D has not been established. We used a single nucleotide polymorphism (SNP) tagging approach to evaluate the association between SNPs in VDR and RXRA and serum levels of 1,25(OH)2D and 25(OH)D. A total of 42 tagSNPs in VDR and 32 in RXRA were analyzed in a sample of 415 participants. Principal components analyses revealed a gene level association between RXRA and serum 1,25(OH)2D concentrations (P=0.01), but not 25(OH)D. No gene-level association was found for VDR with either serum biomarker. At the single-SNP level, a significant positive trend was observed for increasing 1,25(OH)2D levels with each additional copy of the A allele for RXRA SNP rs9409929 (P-trend=0.003). After a multiple comparisons adjustment, no individual SNP in VDR or RXRA was significantly associated with either outcome. These results demonstrate an association between genetic variation in RXRA and 1,25(OH)2D serum concentrations. PMID- 20307662 TI - 24R,25-dihydroxyvitamin D3 [24R,25(OH)2D3] controls growth plate development by inhibiting apoptosis in the reserve zone and stimulating response to 1alpha,25(OH)2D3 in hypertrophic cells. AB - Previously we showed that costochondral growth plate resting zone (RC) chondrocytes response primarily to 24R,25(OH)2D3 whereas prehypertrophic and hypertrophic (GC) cells respond to 1alpha,25(OH)2D3. 24R,25(OH)2D3 increases RC cell proliferation and inhibits activity of matrix processing enzymes, suggesting it stabilizes cells in the reserve zone, possibly by inhibiting the matrix degradation characteristic of apoptotic hypertrophic GC cells. To test this, apoptosis was induced in rat RC cells by treatment with exogenous inorganic phosphate (Pi). 24R,25(OH)2D3 blocked apoptotic effects in a dose-dependent manner. Similarly, apoptosis was induced in ATDC5 cell cultures and 24R,25(OH)2D3 blocked this effect. Further studies indicated that 24R,25(OH)2D3 acts via at least two independent pathways. 24R,25(OH)2D3 increases LPA receptor-1 (LPA R1) expression and production of lysophosphatidic acid (LPA), and subsequent LPA R1/3 dependent signaling, thereby decreasing p53 abundance. LPA also increases the Bcl 2/Bax ratio. In addition, 24R,25(OH)2D3 acts by increasing PKC activity. 24R,25(OH)2D3 stimulates 1-hydroxylase activity, resulting in increased levels of 1,25(OH)2D3, and it increases levels of phospholipase A2 activating protein, which is required for rapid 1alpha,25(OH)2D3-dependent activation of PKC in GC cells. These results suggest that 24R,25(OH)2D3 modulates growth plate development by controlling the rate and extent of RC chondrocyte transition to a GC chondrocyte phenotype. PMID- 20307663 TI - Vitamin D analogs induce lipoxygenase mRNA expression and activity as well as reactive oxygen species (ROS) production in human bone cells. AB - Vitamin D metabolites or its less-calcemic analogs (JKF or QW) are beneficial for bone biology. We analyzed whether or not 25(OH)D3 (25), 1,25(OH)2D3 (1,25), JKF or QW regulate lipooxygenase (LO) enzymes expression and their products hydroxyeicosatetraenoic acid (12 and 15 HETE) formation as well as reactive oxygen species (ROS) production in human bone cell lines (SaOS2 and hFOB) and primary cultured human bone cells (Obs) from males or females. All compounds except 25 increased LOs mRNA expression and HETE production in female or male Obs. ROS formation was induced by JKF and QW in both cell lines, and was inhibited by different inhibitors. Baicalein (baic) an inhibitor of 12 and 15 LO activity, inhibited partially ROS formation by JKF or QW in SaSO2 and hFOB. JKF stimulated DNA synthesis in female Obs was inhibited by baic but unchanged by addition of HETE or HETE with baic. These results indicate that vitamin D increased oxidative stress in bone cells is in part via induction of LO expression and activity. This new feature of vitamin D is probably mediated by intracellular and/or membranal receptors and its potential hazard could lead to potential damage due to increased lipid oxidation. PMID- 20307664 TI - Human breast tumor slices: a model for identification of vitamin D regulated genes in the tumor microenvironment. AB - While many studies have addressed the direct effects of 1alpha,25(OH)2D3 on breast cancer (BC) cells, stromal-epithelial interactions, which are important for the tumor development, have been largely ignored. In addition, high concentrations of the hormone, which cannot be attained in vivo, have been used. Our aim was to establish a more physiological breast cancer model, represented by BC tissue slices, which maintain epithelial-mesenchymal interactions, cultured with a relatively low 1alpha,25(OH)2D3 concentration, in order to evaluate the vitamin D pathway. Freshly excised human BC samples were sliced and cultured in complete culture media containing vehicle, 0.5 nM or 100 nM 1alpha,25(OH)2D3 for 24 h. BC slices remained viable for at least 24 h, as evaluated by preserved tissue morphology in hematoxylin and eosin (HE) stained sections and bromodeoxyuridine (BrdU) incorporation by 10% of tumor cells. VDR mRNA expression was detected in all samples and CYP24A1 mRNA expression was induced by 1alpha,25(OH)2D3 in both concentrations (but mainly with 100 nM). Our results indicate that the vitamin D signaling pathway is functional in BC slices, a model which preserves stromal-epithelial interactions and mimics in vivo conditions. PMID- 20307665 TI - Occult cytomegalovirus in vivarium-housed mice may influence transplant allograft acceptance. AB - We have recently shown that latent murine cytomegalovirus (MCMV) can influence murine transplant allograft acceptance. During these studies we became aware that vivarium-housed control mice can acquire occult MCMV infection. The purpose of this investigation was to confirm occult MCMV transmission and determine the timing, vehicle, and possible consequences of transmission. Mice arriving from a commercial vendor were negative for MCMV both by commercial serologic testing and by our nested PCR. Mice housed in our vivarium became positive for MCMV DNA 30-60 days after arrival, but remained negative for MCMV by commercial serologic testing. To confirm MCMV we sequenced PCR products for several genes and showed >99% homology to MCMV. Further sequence analyses show that the occult MCMV is similar to a laboratory strain of MCMV, but the vehicle of transmission remains unclear. Control tissues from historical experiments with unexplained graft losses were evaluated for occult MCMV, and mice with unexplained allograft losses showed significantly higher incidence of occult MCMV than did allograft acceptors. Deliberate infection with very low titer MCMV confirmed that viral transmission can occur without measurable virus specific antibody or T-cell responses. These data suggest that vivarium-housed mice can develop occult MCMV that is missed by currently available commercial serologic testing, and that these infections may influence transplant allograft acceptance. PMID- 20307666 TI - Transforming growth factor beta 1 (TGF-beta1) and rapamycin synergize to effectively suppress human T cell responses via upregulation of FoxP3+ Tregs. AB - BACKGROUND: The major obstacle faced by patients with type 1 diabetes who undergo islet transplantation is a gradual decline in insulin independence. This decline may reflect alloimmune rejection, autoimmune recurrence and toxicity of drugs such as rapamycin to islet beta cells. Thus, there is a pressing need to refine immunosuppressive protocols in order to reduce toxicity to islet grafts and yet prevent rejection. Recent studies demonstrated that TGF-beta1 is a critical cytokine for the regulation of immune responses. In naive T cells, TGF-beta1 induces FoxP3(+) regulatory T cells and thus could promote transplant tolerance. In this study, in vitro experiments were performed to determine whether TGF-beta1 could synergize with low-dose rapamycin and inhibit T cell activation and production of inflammatory cytokines, as well as enhance FoxP3 expression for potential application in islet transplantation. METHODS: Human peripheral blood mononuclear cells were stimulated with either anti-CD3/CD28 or anti-CD3 during TGF-beta1 and rapamycin treatment. RESULTS: TGF-beta1 inhibited T cell proliferation induced with anti-CD3 stimulation, but not with anti-CD3/CD28 stimulation. The combination of these reagents produced a synergistic inhibition of T cell proliferation induced with both anti-CD3/CD28 and anti-CD3 stimulations. Moreover, TGF-beta1 and rapamycin significantly suppressed cytokine production and induced regulatory T cells by upregulating FoxP3 expression. CONCLUSIONS: These results suggest that the combination of TGF-beta1 and low-dose rapamycin can potently inhibit T cell responses in vivo and would be beneficial in supporting islet graft survival by limiting toxicity and preventing immune rejection. PMID- 20307667 TI - Neuron-selective changes in RNA transcripts related to energy metabolism in toxic models of parkinsonism in rodents. AB - Dopamine (DA) neurons in the substantia nigra (SNDA neurons) are among the most severely affected in Parkinson's disease (PD). Mitochondrial complex I inhibition by rotenone or MPTP can induce SNDA neurodegeneration and recapitulate motor disability in rodents. We performed a transcriptional analysis of the midbrain response to complex I inhibition focused on selected metabolic transcripts using quantitative real-time RT-PCR in conjunction with laser-capture microdissection (LCM) of immunofluorescently targeted SNDA and ventral tegmental area (VTA) DA neurons. There were DA neuron-selective alterations in metabolic transcripts in response to generalized complex I inhibition dependent on the behavioral response of the animal, and vulnerable SNDA neurons were more dynamic in their metabolic transcriptional response than less vulnerable VTADA neurons. The metabolic transcriptional response of DA neurons may contribute significantly to the ultimate toxicity associated with mitochondrial inhibition, and better understanding of this response may provide insight into potential targets for neuroprotection in PD. PMID- 20307668 TI - Stimulation of the rat subthalamic nucleus is neuroprotective following significant nigral dopamine neuron loss. AB - Deep brain stimulation of the subthalamic nucleus (STN-DBS) is efficacious in treating the motor symptoms of Parkinson's disease (PD). However, the impact of STN-DBS on the progression of PD is unknown. Previous preclinical studies have demonstrated that STN-DBS can attenuate the degeneration of a relatively intact nigrostriatal system from dopamine (DA)-depleting neurotoxins. The present study examined whether STN-DBS can provide neuroprotection in the face of prior significant nigral DA neuron loss similar to PD patients at the time of diagnosis. STN-DBS between 2 and 4 weeks after intrastriatal 6-hydroxydopamine (6 OHDA) provided significant sparing of DA neurons in the SN of rats. This effect was not due to inadvertent lesioning of the STN and was dependent upon proper electrode placement. Since STN-DBS appears to have significant neuroprotective properties, initiation of STN-DBS earlier in the course of PD may provide added neuroprotective benefits in addition to its ability to provide symptomatic relief. PMID- 20307670 TI - Visually induced gamma-band activity predicts speed of change detection in humans. AB - Groups of activated neurons typically synchronize in the gamma-frequency band (30 100 Hz), and gamma-band synchronization has been implicated in numerous cognitive functions. Those functions are ultimately expressed as behavior and therefore, functional gamma-band synchronization should be directly related to behavior. We recorded the magnetoencephalogram in human subjects and used a visual stimulus to induce occipital gamma-band activity. We found that the strength of this gamma band activity at a given moment predicted the speed with which the subject was able to report a change in the stimulus. This predictive effect was restricted in time, frequency and space: It started only around 200 ms before the behaviorally relevant stimulus change, was present only between 50 and 80 Hz, and was significant only in bilateral middle occipital gyrus, while the peak of overall visually induced gamma-band activity was found in the calcarine sulcus. These results suggest that visually induced gamma-band activity is functionally relevant for the efficient transmission of stimulus change information to brain regions issuing the corresponding motor response. PMID- 20307671 TI - Molecular phylogeny and DNA barcoding in the meadow-spittlebug Philaenus spumarius (Hemiptera, Cercopidae) and its related species. AB - Philaenus spumarius, widely studied for its colour/pattern polymorphism, is a widespread species across the Holartic. The patterns of haplotype divergence at the mitochondrial gene cytochrome oxidase I (COI) found in this study suggest a postglacial western Europe (Iberian and Italian peninsulas to Britain) and a eastern (from Near East to Finland) south-to-north colonization. The haplotypes found in North America are most likely derived from the British haplotypes. The barcode fragment used here allowed the distinction of the species within genus Philaenus and questioned some taxonomic identifications of sequences present in Genbank. PMID- 20307672 TI - Phylogeny of the mourning wheatear Oenanthe lugens complex. AB - The phylogenetic relationship of many species and subspecies within the genus Oenanthe (wheatears) is still debated. Only recently molecular approaches have been used to clarify their basal taxonomy. One of the main unsolved groups is summarized under the name mourning wheatear O. lugens, which comprises depending on the underlying species concept 3-8 different taxa. These include the wheatears of the subspecies group lugens (halophila, lugens, persica), the subspecies group lugubris (lugubris, schalowi, vauriei), and the subspecies group lugentoides (lugentoides, boscaweni). In order to shed light on this unsolved issue we studied the taxonomy of the mourning wheatear complex by means of molecular markers and comparative morphometry. We found reasonable evidence to follow a narrow species concept treating all the three subspecies groups of the mourning wheatear in future as three independent taxonomic entities (super-species O. lugens, O. lugentoides, O. lugubris). Further within the subspecies group O. lugens we suggest treating halophila and lugens as members of the polytypic species O. lugens, while the Persian mourning wheatear O. persica merits the status of an independent monotypic species, endemic to the Iranian Plateau. Genetic and morphometric characters support a long separation of this form (a half to one Million years). For the black form "basalti" from Syria and Jordan our molecular data indicates a close relationship to lugens and this form is therefore probably best treated as a colour morph of lugens, adapted to the local habitat conditions. However, future behavioural studies have to show if there exist prezygotic barriers between both forms. PMID- 20307669 TI - A mobile threat to genome stability: The impact of non-LTR retrotransposons upon the human genome. AB - It is now commonly agreed that the human genome is not the stable entity originally presumed. Deletions, duplications, inversions, and insertions are common, and contribute significantly to genomic structural variations (SVs). Their collective impact generates much of the inter-individual genomic diversity observed among humans. Not only do these variations change the structure of the genome; they may also have functional implications, e.g. altered gene expression. Some SVs have been identified as the cause of genetic disorders, including cancer predisposition. Cancer cells are notorious for their genomic instability, and often show genomic rearrangements at the microscopic and submicroscopic level to which transposable elements (TEs) contribute. Here, we review the role of TEs in genome instability, with particular focus on non-LTR retrotransposons. Currently, three non-LTR retrotransposon families - long interspersed element 1 (L1), SVA (short interspersed element (SINE-R), variable number of tandem repeats (VNTR), and Alu), and Alu (a SINE) elements - mobilize in the human genome, and cause genomic instability through both insertion- and post-insertion-based mutagenesis. Due to the abundance and high sequence identity of TEs, they frequently mislead the homologous recombination repair pathway into non-allelic homologous recombination, causing deletions, duplications, and inversions. While less comprehensively studied, non-LTR retrotransposon insertions and TE-mediated rearrangements are probably more common in cancer cells than in healthy tissue. This may be at least partially attributed to the commonly seen global hypomethylation as well as general epigenetic dysfunction of cancer cells. Where possible, we provide examples that impact cancer predisposition and/or development. PMID- 20307673 TI - Phylogeography of the Middle Eastern tree frogs (Hyla, Hylidae, Amphibia) as inferred from nuclear and mitochondrial DNA variation, with a description of a new species. AB - Evolutionary relationships of the tree frogs from the Middle East and the demographic histories of their populations were studied using a combination of mitochondrial and nuclear genes. Hyla savignyi and neighboring populations of H. orientalis (former eastern populations of H. arborea) were the main focus taxa. Within H. savignyi, a deep phylogenetic divergence dated about 8.4Ma was discovered. Southern populations from Yemen, Jordan, southern Syria and extreme north-eastern Israel are hereby described as a new species, H. felixarabica sp. nov. Our study points to a biogeographic connection of the south-western Arabian Peninsula and southern Levant and to the importance of the Dead Sea Rift as a historical barrier geographically separating the new species from H. savignyi. Major genetic breaks revealed within species (H. felixarabica: Yemen vs. Jordan Syria; H. savignyi sensu stricto: Levant vs. Turkey-Iran) are probably connected to climate changes during the Plio-Pleistocene boundary, while the finer phylogeographic structuring probably resulted from the Quaternary climate oscillations. The Cypriote population of H. savignyi originated from southern Anatolia relatively recently. Hyla orientalis from the southern Black Sea region seems to be genetically quite uniform, although two phylogeographic units with western Turkish and Caucasus-Caspian affinities might be detected. Hyla savignyi and H. orientalis carry signals of population expansions dated to the middle to late Pleistocene, while populations of H. felixarabica seem to have rather been constant in size, which might indicate more stable climatic conditions in the southern regions during the Quaternary. PMID- 20307674 TI - Neotropical mutualism between Acacia and Pseudomyrmex: phylogeny and divergence times. AB - The interaction between Acacia and Pseudomyrmex is a textbook example of mutualism between ants and plants, nevertheless aspects of its evolutionary biology have not been formally explored. In this paper we analyze primarily the phylogenies of both New World Acacia and of their associated species of ants, and the geographic origin of this mutualism. Until now, there has been no molecular analysis of this relationship in terms of its origin and age. We analyzed three chloroplast markers (matK, psaB-rps14, and trnL-trnF) on a total of 70 taxa of legumes from the subfamily Mimosoideae, and two nuclear regions (long-wavelength rhodopsine and wingless) on a total of 43 taxa of ants from subfamily Pseudomyrmecinae. The monophyly of subgenus Acacia and within the New World lineages that of the myrmecophilous Acacia group was established. In addition, our results supported the monophyly of the genus Pseudomyrmex and of the associated acacia-ants P. ferrugineus group. Using Bayesian methods and calibration data, the estimated divergence times for the groups involved in the mutualism are: 5.44+/-1.93 My for the myrmecophilous acacias and 4.58+/-0.82 My for their associated ant species, implying that their relationship originated in Mesoamerica between the late Miocene to the middle Pliocene, with eventual diversification of both groups in Mexico. PMID- 20307675 TI - Divergence times and colonization of the Canary Islands by Gallotia lizards. AB - The Canary Islands have become a model region for evolutionary studies. We obtained 1.8 Kbp of mtDNA sequence from all known island forms of the endemic lizard genus Gallotia and from its sister taxon Psammodromus in order to reanalyze phylogenetic relationships within the archipelago, estimate lineage divergence times, and reconstruct the colonization history of this group. Well supported phylogenies were obtained using maximum parsimony and Bayesian inference. Previous studies have been unable to establish the branching pattern at the base of the tree. We found evidence that G. stehlini (Gran Canaria) originated from the most basal Gallotia node and G. atlantica from the subsequent node. Divergence times were estimated under a global clock using Bayesian Markov Chain Monte Carlo methods implemented by three different programs: BEAST, MCMCTREE, MULTIDIVTIME. Node constraints were derived from subaerial island appearance data and were incorporated into the analyses as soft or hard maximal bounds. Posterior node ages differed slightly between programs, possibly due to different priors on divergence times. The most eastern Canary Islands first emerged just over 20 mya and their colonization appears to have taken place relatively quickly, around 17-20 mya. The subsequent node is consistent with cladogenesis due to colonization of Gran Canaria from the eastern islands about 11-13 mya. The western islands appear to have been colonized by a dispersal event from Lanzarote/Fuerteventura in the east to either La Gomera or one of the ancient edifices that subsequently formed Tenerife in the west, about 9-10 mya. Within the western islands, the most recent node that is ancestral to both the G. intermedia/G. gomerana/G. simonyi and the G.galloti/G. caesaris clades is dated at about 5-6 mya. Subsequent dispersal events between ancient Tenerife islands and La Gomera are dated at around 3 mya in both clades, although the direction of dispersal cannot be determined. Finally, we show that G. galloti is likely to have colonized La Palma more than 0.5 Ma after emergence of the island 1.77 mya, while G. caesaris from the same clade may have colonized El Hierro very soon after it emerged 1.12 mya. There are tentative indications that the large-bodied endangered G. simonyi colonized El Hierro around the same time or even later than the smaller-bodied G. caesaris. This study demonstrates the effectiveness of Bayesian dating of a phylogeny in helping reconstruct the historical pattern of dispersal across an oceanic archipelago. PMID- 20307676 TI - Marine biogeographic boundaries and human introduction along the European coast revealed by phylogeography of the prawn Palaemon elegans. AB - A phylogeographic analysis is carried out for the widely distributed European littoral prawn Palaemon elegans in order to test for potential genetic differentiation and geographic structure. Mitochondrial sequences were obtained from 283 specimens from the northeastern Atlantic, the Baltic, Mediterranean, Black and Caspian Seas. Our study revealed a surprisingly complex population structure. Three main haplogroups can be separated: one from the Atlantic (Type I) and two from the Mediterranean (Types II and III). While the Mediterranean types occur in sympatry, a clear phylogeographic break was observed along the Almeria-Oran Front separating Type I and giving evidence for a genetic isolation of Atlantic and Mediterranean populations. Type III represents the most distinct haplogroup with high levels of nucleotide divergence, indicating the occurrence of a cryptic species with a Messinian origin. The colonization of the southeastern Baltic Sea is most likely due to human introduction. PMID- 20307677 TI - c-Fos expression is elevated in GABAergic interneurons of the gustatory cortex following novel taste learning. AB - Long-term sensory memories are considered to be stored in the relevant cortical region subserving the given modality. We and others have recently identified a series of molecular alterations in the gustatory cortex (GC) of the rat at different time intervals following novel taste learning. Some of these correlative modifications were also necessary for taste memory acquisition and/or consolidation. However, very little is known about the localization of these molecular modifications within the GC or about the functional activation of the GC hours after novel taste learning. Here, we hypothesize that inhibitory interneurons are activated in the GC on a scale of hours following learning and used c-Fos expression and confocal microscopy with different markers to test this hypothesis. We found that GABAergic interneurons are activated in the GC in correlation with novel taste learning. The activation was evident in the deep but not superficial layers of the dysgranular insular cortex. These results suggest that the GABAergic machinery in the deep layers of the GC participates in the processing of taste information hours after learning, and provide evidence for the involvement of a local cortical circuit not only during acquisition of new information but also during off-line processing and consolidation of taste information. PMID- 20307678 TI - The effect of post-learning presentation of music on long-term word-list retention. AB - Memory consolidation processes occur slowly over time, allowing recently formed memories to be altered soon after acquisition. Although post-learning arousal treatments have been found to modulate memory consolidation, examination of the temporal parameters of these effects in humans has been limited. In the current study, 127 participants learned a neutral word list and were exposed to either a positively or negatively arousing musical piece following delays of 0, 20 or 45min. One-week later, participants completed a long-term memory recognition test, followed by Carver and White's (1994) approach/avoidance personality scales. Retention was significantly enhanced, regardless of valence, when the emotion manipulation occurred at 20min, but not immediately or 45min, post learning. Further, the 20min interval effect was found to be moderated by high 'drive' approach sensitivity. The selective facilitatory conditions of music identified in the current study (timing and personality) offer valuable insights for future development of more specified memory intervention strategies. PMID- 20307679 TI - Platelet adhesion and intracellular calcium levels in antigen-challenged rats. AB - There is considerable evidence that platelet activation occurs in allergic airways diseases. In this study we aimed to investigate platelet adhesion to immobilized fibrinogen and intracellular calcium levels in a rat model of allergic inflammation. Male Wistar rats were challenged with ovalbumin (OVA). At 30 min to 24h after OVA-challenge, assays of platelet adhesion to immobilized fibrinogen and intracellular calcium levels using fura 2-AM loaded platelets were performed. The serum levels of IgE were approximately 5-fold greater in OVA sensitized rats. A marked eosinophil influx in bronchoalveolar lavage (BAL) fluid of OVA-challenged rats at 24h after OVA-challenge was also seen. OVA-challenge resulted in a marked thrombocytopenia, as observed within 12h after OVA challenge. The agonists ADP (0.5-50 microM) and thrombin (30-100 mU/ml) concentration-dependently increased platelet adhesion to immobilized fibrinogen. At an early time after OVA-challenge (30 min), platelets exhibited greater platelet adhesion compared with the non-sensitized group, whereas at a late time (24h) they exhibited lower platelet adhesion to both agonists. Moreover, at 30 min after OVA-challenge, intracellular calcium levels to ADP (20 microM) and thrombin (100 mU/ml)-activated platelets were greater compared with non challenged rats. As opposed, at 24h after OVA challenge, a lower intracellular calcium level to ADP- and thrombin-activated platelets was observed. In conclusion, OVA-challenge in rats promotes a biphasic response in platelet adhesion consisting of an increased adhesion and intracellular calcium levels at an early phase (30 min), which progress to a reduction in adhesion and intracellular calcium levels at a late time (24h) after antigen challenge. PMID- 20307681 TI - Effect of formoterol and budesonide on chemokine release, chemokine receptor expression and chemotaxis in human neutrophils. AB - Severe persistent asthma and chronic obstructive pulmonary disease (COPD) are associated with neutrophil influx into the airways. It is not clear whether neutrophil chemotaxis is influenced by beta(2)-agonists and glucocorticoids, drugs commonly used in treatment of asthma and COPD. The effect of a long-acting beta(2)-agonist (formoterol), and a glucocorticosteroid (budesonide) on chemokine/cytokine release (CXCL8, CXCL1, IL-6), regulation of chemokine receptors (CXCR1, CXCR2), and migration were assessed in neutrophils from 10 non allergic, healthy donors. Formoterol enhanced and budesonide inhibited IL-6, CXCL8 and CXCL1 release from LPS-stimulated neutrophils. Formoterol up-regulated both CXCR1 and CXCR2 expression, whereas budesonide up-regulated the expression of CXCR2 only. Despite the effects on chemokine release and drug-induced up regulation of CXCR1 and CXCR2, no influence on neutrophil chemotaxis could be demonstrated. We conclude that a beta(2)-agonist and a glucocorticoid, commonly used in the treatment of obstructive lung diseases, influence chemokine release and receptor sensitivity but the functional consequences of these findings remain unclear. PMID- 20307680 TI - Impact of infusion method on amikacin serum levels in humans. AB - Aminoglycosides are broad-spectrum antibiotics with peak-dependent bactericidal activity, administered by gravity infusion or for more accuracy by electronic pump infusion. The aim of this study was to assess the difference between the two systems and its pharmacokinetic impact. Twenty-four patients hospitalised for community-acquired pulmonary infections received amikacin by IV route over 1 h with a targeted peak concentration of 35 mg/L. They were randomly distributed into two groups, one receiving infusion through a pump system, the other by gravity. Amikacin serum levels were determined at the end of infusion and 24 h later. C(max) values were significantly lower with gravity than pump (40.2 +/- 12.3 vs. 50.6 +/- 17.6 mg/L, respectively; p = 0.04). Elimination half-life time, volume of distribution and clearance did not differ significantly from one group to the other. The percentage of patients who failed to achieve the targeted peak concentration was significantly higher with gravity than pump (41.7% vs. 16.7%, respectively; p < 0.001). Improving infusion flow-rate provides better control over amikacin C(max). This study underlines the fact that infusion device characteristics should be added to the physiopathological information of a patient if we are to make a better estimation of pharmacokinetic parameters. PMID- 20307682 TI - Growth of the chicken embryo: implications of egg size. AB - Among avian species with large differences in egg size, changes in eggshell conductance and incubation time permit the water loss necessary for embryonic development. To what extent this happens for different-size eggs within a species is much less known. Chicken eggs with fresh egg weight (Wegg) either large (L, approximately 66 g) or small (S, approximately 51 g) were incubated at 38 degrees C and 60% humidity; their yolk and albumen scaled almost in proportion to Wegg. Eggshell gas conductance scaled to 0.77 of Wegg, as it occurs inter-specifically, while external pipping and hatching occurred at similar times in S and L. Hence, L lost less water during incubation than S, and embryos of L were over-hydrated and those of S were dehydrated. The absolute values of embryo's weight, growth rate, oxygen consumption and the weight of the chorioallantoic membrane were similar between S and L during the first half of incubation, and greater in L in the second half. Incubation in hypoxia reduced growth rate in both sets and maintained the difference in growth trajectories between S and L. The energetic cost of growth and tissue maintenance did not differ significantly. It is concluded that, among chicken eggs of different sizes, 1) the growth rate of the embryo relates to the size of its egg, probably genetically and because of differences in water content, 2) eggshell conductance contributes, but incubation time does not, to the requirements for water loss. Therefore, the egg water balance during incubation may be the physiological constraint that limits the maximal variability in egg size compatible with embryonic survival. PMID- 20307683 TI - Pim-2 phosphorylation of p21(Cip1/WAF1) enhances its stability and inhibits cell proliferation in HCT116 cells. AB - Pim-2 kinase is one of the three highly conserved Pim family members which are known to be involved in cell survival and cell proliferation. Here we demonstrate that like Pim-1, Pim-2 also phosphorylates the cell cycle inhibitor p21(Cip1/WAF1) (p21) on Thr145 in vitro and in vivo. Overexpression of Pim-2 in HCT116 cells leads to the increased stability of p21 and results in enhanced levels of both exogenous and endogenous p21 proteins. Knockdown of Pim-2 expression via siRNA results in reduced level of endogenous p21, indicating that like Pim-1, Pim-2 is another legitimate p21 kinase. However, Pim-2 has no influence on the nuclear localization of p21 in HCT116 cells. In addition, Pim-2 is able to arrest the cell cycle at G1/S phase and inhibit cell proliferation through phosphorylation of p21 in HCT116 cells. These data suggest that Pim-2 phosphorylation of p21 enhances p21's stability and inhibits cell proliferation in HCT116 cells. PMID- 20307685 TI - Alkylation of sperm DNA is associated with male factor infertility and a reduction in the proportion of oocytes fertilised during assisted reproduction. AB - Approximately one-third of IVF cases in the UK are attributed to male factor infertility and in the majority of cases the origin of male infertility is unknown. The integrity of sperm DNA is important both for the success of assisted reproduction and the implications for the off-spring. One type of DNA damage that has not been investigated with respect to fertility outcomes is the adduct N7 methyldeoxyguanosine (N7-MedG), a biomarker for exposure to alkylating agents. A prospective cohort of couples attending for IVF had their N7-MedG levels in sperm measured using an immunoslot blot technique to examine whether sperm N7-MedG levels are associated with male factor infertility, semen quality measures or assisted reproduction outcomes. Sufficient DNA for analysis was obtained from 67/97 couples and N7-MedG was detected in 94% of sperm samples analysed. Men diagnosed with male factor infertility had significantly higher mean levels of N7 MedG in their sperm DNA (P=0.03). Logistic regression analysis showed that N7 MedG levels were significantly negatively associated with the proportion of oocytes successfully fertilised irrespective of the method of fertilisation used (IVF or intra-cytoplasmic sperm injection; ICSI, P<0.001). Therefore exposure to DNA alkylating agents is significantly associated with male infertility and the proportion of oocytes fertilised during assisted reproduction. Reducing such exposure may improve male fertility but further work is required to determine the relative importance of exogenous and endogenous sources of exposure. PMID- 20307684 TI - Cascades of transcription regulation during liver regeneration. AB - An increasing demand for new strategies in cancer prevention and regenerative medicine requires a better understanding of molecular mechanisms that control cell proliferation in tissue-specific manner. Regenerating liver is a unique model allowing use of biochemical, genetic, and engineering tools to uncover molecular mechanisms and improve treatment of hepatic cancers, liver failure, and fibrotic disease. Molecular mechanisms of liver regeneration involve extra- and intracellular factors to activate transcription of genes normally silenced in quiescent liver. While many upstream signaling pathways of the regenerating liver have been extensively studied, our knowledge of the downstream effectors, transcription factors (TFs), remains limited. This review describes consecutive engagement of pre-existing and de novo synthesized TFs, as cascades that regulate expression of growth-related and metabolic genes during liver regeneration after partial hepatectomy in mice. Several previously recognized regulators of regenerating liver are described in the light of recently identified co-activator and co-repressor complexes that interact with primary DNA-binding TFs. Published results of gene expression and chromatin immunoprecipitation analyses, as well as studies of transgenic mouse models, are used to emphasize new potential regulators of transcription during liver regeneration. Finally, a more detailed description of newly identified transcriptional regulators of liver regeneration illustrates the tightly regulated balance of proliferative and metabolic responses to partial hepatectomy. PMID- 20307686 TI - Genetic activities in micronuclei: is the DNA entrapped in micronuclei lost for the cell? AB - Micronuclei are good markers of genotoxic exposure in humans and their scoring has been extensively used to identify potential genotoxic agents. Micronuclei are also indicators of chromosomal instability, since the frequency of micronuclei is higher in tumour cells and cells with a defective DNA damage repair system or disrupted cell cycle checkpoint machinery. Despite the widespread use of this biomarker, information on the basic biology of micronuclei and the impact of micronuclei on the cell is relatively controversial. In some cell systems, micronuclei are considered to be genetic material that is lost for the cell; whereas other studies suggest that micronuclear DNA is actively transcribed and its genes are fully expressed. Recently, evidence has accumulated suggesting that damaged DNA entrapped in micronuclei induces a defective cell cycle checkpoint arrest and DNA repair response, and that micronuclear content can be degraded without inducing an immediate cell cycle arrest or causing the cell to enter apoptosis. Overall, these findings emphasise the important consequences of micronucleus formation in terms of chromosomal instability in general and gene loss in particular. PMID- 20307687 TI - Target proteins of the cytosolic thioredoxin in Plasmodium falciparum. AB - The target proteins of a cytosolic Trx (PfTrx-1) in Plasmodium falciparum with Trx-affinity chromatography were examined. Based on the Trx protein reduction pathway, we generated a cysteine mutant of PfTrx-1, which captures the target protein as a mixed disulfide intermediate. A number of proteins were captured with PfTrx-1(C33S) immobilized on resin and were eluted by DTT treatment. The PfTrx-1(C33S) immobilized resin-captured proteins were trypsin-digested and analyzed on a liquid chromatography-mass spectrometry system. Analysis of the sequence data against databases assigned 20 proteins, four of which had been found previously in P. falciparum, with the remaining 16 being new targets. The potential Trx-target proteins included those in pathways such as the redox cycle, protein biosynthesis, energy metabolism and signal transduction. We captured 4 enzymes in the glycolysis pathway (hexokinase, glyceraldehyde-3-phosphate dehydrogenase (GAPDH), phosphoglycerate mutase and L-lactate dehydrogenase (LDH)) as Trx-targets, and we found that PfTrx-1 enhanced the activity of PfGAPDH and PfLDH. PMID- 20307688 TI - Cardiac mast cell proteases do not contribute to the regulation of the rat coronary vascular responsiveness to arterial delivered angiotensin I and II. AB - Cardiac mast cells (MC) are apposed to capillaries within the heart and release renin and proteases capable of metabolizing angiotensins (Ang). Therefore, we hypothesized that mast cell degranulation could alter the rat coronary vascular responsiveness to the arterial delivered Ang I and Ang II, taking into account carboxypeptidase and chymase-1 activities. Hearts from animals that were either pretreated or not with systemic injection of the secretagogue compound 48/80 were isolated and mounted on a Langendorff apparatus to investigate coronary reactivity. The proteolytic activity of the cardiac perfusate from isolated hearts, pretreated or not with the secretagogue, toward Ang I and tetradecapeptide renin substrate was analyzed by HPLC. Coronary vascular reactivity to peptides was not affected by compound 48/80 pretreatment, despite the extensive amount of cardiac MC degranulation. Cardiac MC activation did not modify the generation of both Ang II and Ang 5-10 from Ang I by cardiac perfusate, activities that could be ascribed to MC carboxypeptidase and chymase 1, respectively. An aliskiren-resistant Ang I-forming activity was increased in perfusates from secretagogue-treated hearts. Thus, cardiac MC proteases capable of metabolizing angiotensins do not affect rat coronary reactivity to arterial delivered Ang I and II. PMID- 20307689 TI - Genetic association of Toll-like-receptor 4 and tumor necrosis factor-alpha polymorphisms with Plasmodium falciparum blood infection levels. AB - Dysregulated innate immune responses due to inappropriate signaling by Toll-like receptors (TLRs) and aberrant production of pro-inflammatory cytokines are implicated in the immunopathology and disease outcome in Plasmodium falciparum malaria. This study investigates the relationship between polymorphic variability of candidate genes including TLR-2, -4, -9, tumor necrosis factor-alpha and lymphotoxin-alpha and blood infection level in Indian mild malaria patients. Genotyping was carried out by PCR-RFLP and sequencing. Association of parasite load with genotypes was examined using model based and model free approaches. Allele and haplotype based risk assessment for disease severity was performed by stratifying the patients into high and low parasitemic groups on the basis of a threshold value derived by employing a two-component mixture model and expectation-maximization algorithm. The mean parasitemia was significantly increased for variant homozygous genotype (C/C) at TNF-alpha promoter -1031 and major homozygous genotypes encoding Asp/Asp and Thr/Thr at codons 299 and 399, respectively, on TLR4 polypeptide. Individuals harboring combined genotype C/C Asp/Asp-Thr/Thr on TNF-alpha and TLR4 presented the highest parasite load. The frequencies of variant allele C in TNF-1031 (OR=1.91 with 95% CI=1.24-2.94) and TNF-alpha promoter haplotypes C-C-G-G (OR=1.99 with 95% CI=1.21-3.27) and C-C-G-A (OR=2.96 with 95% CI=1.19-7.37) pertaining to loci TNF-1031/-857/-308/-238 were significantly elevated in the high parasitemic group. On the contrary, the frequencies of variant allele encoding Ile at 399 (OR=0.55 with 95% CI=0.32-0.94) and haplotype corresponding to Gly-Ile (299-399) (OR=0.51 with 95% CI=0.28-0.9) in TLR4 were higher in low parasitemic group. In silico analysis indicate differential binding of transcription factors to TNF-alpha promoter haplotypes and alteration in the surface charge distribution of the TLR4 variant proteins. Our results support a genetic role of TLR4 and TNF-alpha in controlling the blood infection level in mild malaria. PMID- 20307690 TI - Bisphosphonates in patients with autoimmune rheumatic diseases: Can they be used in women of childbearing age? AB - Autoimmune rheumatic diseases (ARD) are prevalent in women during their childbearing age. For their treatment, high doses of corticosteroid (CS) for long term periods are often required, increasing the risk of bone loss. According to recent guidelines, bisphosphonates (BP) should be used as first line treatment to prevent CS induced osteoporosis. However, due to their long-term release from bone and their ability to cross the placenta, it has been suggested to avoid BP in women during their fertile years. BP seem to decrease foetus bone length in pregnant animals, but not in humans, at least, when they are administered at therapeutic dosage. BP are embryo toxic in animals when used at high dosage. In a systematic literature review, we found 58 women treated with BP close before or during pregnancy, showing no related congenital malformations. However, the Unit of Clinical and Epidemiological Genetics in University of Padova collected ten cases of women treated with BP during pregnancy, reporting 20% of congenital malformations. Thus, we suggest to avoid BP during pregnancy and caution with their use in fertile women. When they have to be given before pregnancy, specific affinities of the BP have to be considered to plan the washout period beforehand. PMID- 20307691 TI - Central chemoreception: lessons from mouse and human genetics. AB - The response to increased P(CO(2)) in the brain is an essential drive to breathe and required for CO(2) and pH homeostasis in the blood, but where and how CO(2) is sensed are still contentious issues. Here, we review evidence from mouse and human genetics that argue for the crucial role in CO(2) chemosensitivity of a limited set of central neurons that express the Phox2b transcription factor and are disabled by Phox2b mutations. A common trait of different Phox2b mutations that impair CO(2) responsiveness in the embryo and respiration in neonates is the depletion of Phox2b-expressing neurons in the retrotrapezoid nucleus, providing genetic evidence for their importance for proper breathing and central chemosensitivity at birth. PMID- 20307692 TI - Polyglutamine tract-binding protein-1 binds to U5-15kD via a continuous 23 residue segment of the C-terminal domain. AB - Polyglutamine tract-binding protein-1 (PQBP-1) is a nuclear protein that interacts with various proteins, including RNA polymerase II and the spliceosomal protein U5-15kD. PQBP-1 is known to be associated with X-linked mental retardation in which a frameshift mutation in the PQBP-1 gene occurs. In the present study, we demonstrate that PQBP-1 binds to U5-15kD via a continuous 23 residue segment within its C-terminal domain. Intriguingly, this segment is lost in the frameshift mutants of PQBP-1 associated with X-linked mental retardation. These findings suggest that the frameshift mutations in the PQBP-1 gene lead to expression of mutants lacking the ability to interact with U5-15kD. PMID- 20307693 TI - Encapsulation of fibroblasts causes accelerated alginate hydrogel degradation. AB - Calcium-alginate hydrogel has been widely studied as a material for cell encapsulation for tissue engineering. At present, the effect that cells have on the degradation of alginate hydrogel is largely unknown. We have shown that fibroblasts encapsulated at a density of 7.5 x 10(5) cells ml(-1) in both 2% and 5% w/v alginate remain viable for at least 60 days. Rheological analysis was used to study how the mechanical properties exhibited by alginate hydrogel changed during 28 days in vitro culture. Alginate degradation was shown to occur throughout the study but was greatest within the first 7 days of culture for all samples, which correlated with a sharp release of calcium ions from the construct. Fibroblasts were shown to increase the rate of degradation during the first 7 days when compared with acellular samples in both 2% and 5% w/v gels, but after 28 days both acellular and cell-encapsulating samples retained disc-shaped morphologies and gel-like spectra. The results demonstrate that although at an early stage cells influence the mechanical properties of encapsulating alginate, over a longer period of culture, the hydrogels retain sufficient mechanical integrity to exhibit gel-like properties. This allows sustained immobilization of the cells at the desired location in vivo where they can produce extracellular matrix and growth factors to expedite the healing process. PMID- 20307694 TI - Chitosan-poly(lactide-co-glycolide) microsphere-based scaffolds for bone tissue engineering: in vitro degradation and in vivo bone regeneration studies. AB - Natural polymer chitosan and synthetic polymer poly(lactide-co-glycolide) (PLAGA) have been investigated for a variety of tissue engineering applications. We have previously reported the fabrication and in vitro evaluation of a novel chitosan/PLAGA sintered microsphere scaffold for load-bearing bone tissue engineering applications. In this study, the in vitro degradation characteristics of the chitosan/PLAGA scaffold and the in vivo bone formation capacity of the chitosan/PLAGA-based scaffolds in a rabbit ulnar critical-sized-defect model were investigated. The chitosan/PLAGA scaffold showed slower degradation than the PLAGA scaffold in vitro. Although chitosan/PLAGA scaffold showed a gradual decrease in compressive properties during the 12-week degradation period, the compressive strength and compressive modulus remained in the range of human trabecular bone. Chitosan/PLAGA-based scaffolds were able to guide bone formation in a rabbit ulnar critical-sized-defect model. Microcomputed tomography analysis demonstrated that successful bridging of the critical-sized defect on the sides both adjacent to and away from the radius occurred using chitosan/PLAGA-based scaffolds. Immobilization of heparin and recombinant human bone morphogenetic protein-2 on the chitosan/PLAGA scaffold surface promoted early bone formation as evidenced by complete bridging of the defect along the radius and significantly enhanced mechanical properties when compared to the chitosan/PLAGA scaffold. Furthermore, histological analysis suggested that chitosan/PLAGA-based scaffolds supported normal bone formation via intramembranous formation. PMID- 20307695 TI - Molecular analysis of Chanarin-Dorfman syndrome (CDS) patients: Identification of novel mutations in the ABHD5 gene. AB - Chanarin-Dorfman syndrome (CDS) is an autosomal recessive metabolic disorder associated with congenital ichthyosis and a multisystemic accumulation of neutral lipids in various types of cells. Recently, mutations of the ABHD5 gene were identified as the cause of CDS. In this work, we carried out molecular analysis of the ABHD5 gene in 6 unrelated patients. We identified one previously reported mutation, N209X and two novel genetic alterations; a nonsense mutation (p.Y50X) and missense mutation (p.S73A). PMID- 20307696 TI - Measurement in psychosomatic research. PMID- 20307697 TI - Introduction to health measurement scales. AB - Both research and clinical decision making rely on measurement scales. These scales vary with regard to their psychometric properties, ease of administration, dimensions covered by the scale, and other properties. This article reviews the main psychometric characteristics of scales and assesses their utility. PMID- 20307698 TI - Pediatric consultation-liaison psychiatry. PMID- 20307699 TI - Measurement of self-reported pain intensity in children and adolescents. AB - Acute and chronic pain is a common experience in children and youth. A thorough assessment is fundamental to understand this experience and to assess and monitor treatment responses. The intensity of pain is the parameter most commonly assessed. In this article, we describe the different methods employed to assess pediatric pain intensity and review well-validated and commonly used self-report measures of pain. This review is based on the recent systematic reviews conducted for the Pediatric Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials Consensus Group and the Society of Pediatric Psychology. Amongst the several types of pediatric pain measures, self-report, when available, is regarded as the primary source of information about pain intensity, to be complemented by observation and knowledge of the context. There is a large number of self-report measures of pediatric pain intensity; and there is some agreement that professionals in the clinical and research practice should assess pain intensity using the Pieces of Hurt Tool, the Faces Pain Scale, the Oucher, or Visual Analogue Scales because these measures have shown to have sound psychometric properties and clinical utility. Despite the increased number of age appropriate self-report measures of pediatric pain intensity over the last years, we report several research gaps and priorities of future research. PMID- 20307700 TI - Delirium in children and adolescents: A systematic review of the literature. AB - OBJECTIVES: The purpose of this study was to collate all works relating to delirium and probable delirium in children and adolescents published since 1980. METHODS: A systematic review of the literature in all languages published between 1980 and March 2009 was conducted. RESULTS: The literature is limited to small case series and case reports including a total of 217 children or adolescents with definite delirium and a further 136 children and adolescents with "probable delirium." These articles, in addition to unsystematic reviews, overviews, editorials, journal commentaries, and pertinent book chapters, are discussed in relation to prevalence, predisposing and precipitating factors, phenomenology, residual psychopathology, mortality, management, and prevention of delirium in childhood and adolescence. CONCLUSIONS: Delirium is an important but neglected disorder of childhood associated with significant morbidity and high mortality. Current clinical practice for management is based on slim empirical evidence. PMID- 20307701 TI - A medical record review for functional somatic symptoms in children. AB - OBJECTIVE: The objectives of this study were to develop and test a systematic medical record review for functional somatic symptoms (FSSs) in paediatric patients and to estimate the inter-rater reliability of paediatricians' recognition of FSSs and their associated impairments while using this method. METHODS: We developed the Medical Record Review for Functional Somatic Symptoms in Children (MRFC) for retrospective medical record review. Described symptoms were categorised as probably, definitely, or not FSSs. FSS-associated impairment was also determined. Three paediatricians performed the MRFC on the medical records of 54 children with a diagnosed, well-defined physical disease and 59 with 'symptom' diagnoses. The inter-rater reliabilities of the recognition and associated impairment of FSSs were tested on 20 of these records. RESULTS: The MRFC allowed identification of subgroups of children with multisymptomatic FSSs, long-term FSSs, and/or impairing FSSs. The FSS inter-rater reliability was good (combined kappa=0.69) but only fair as far as associated impairment was concerned (combined kappa=0.29). CONCLUSIONS: In the hands of skilled paediatricians, the MRFC is a reliable method for identifying paediatric patients with diverse types of FSSs for clinical research. However, additional information is needed for reliable judgement of impairment. The method may also prove useful in clinical practice. PMID- 20307702 TI - Structured education program improves the coping with atopic dermatitis in children and their parents-a multicenter, randomized controlled trial. AB - OBJECTIVE: The objective of this study was to prove training-specific effects in children with atopic dermatitis (AD) and their parents concerning coping with the disease after their participation in a training program. In the 1-year follow-up, the changes in the training group were compared to the changes in a waiting control group while controlling the effects of the changes in severity scores. METHODS: One hundred eighty-five children aged 8-12 years and their parents participated in the study. Complete data sets at the 1-year follow-up were available for 185 parent-child pairs (102 training group; 83 waiting control group). In addition to the severity of the AD [measured with the Scoring Atopic Dermatitis (SCORAD)], data on children's itching-scratching cognitions and coping behavior and on parents handling their affected children were used in the analysis. To study whether the intervention group experienced an additional psychological benefit, which is not due to the SCORAD values, analyses of covariance with repeated measures with standardized residual change scores of the SCORAD as covariate were calculated. RESULTS: The intervention group showed greater improvement in children's coping behavior and in parents' handling their affected children. Additional effects of the training program not due to somatic improvement could be seen in the scales of itching-scratching cognitions and in three of four scales on parents dealing with their affected children. CONCLUSION: The training program, which was tested in the German Atopic Dermatitis Intervention Study, had effects on almost all explored psychological variables. Therefore, additional psychological benefit in the training group does not only depend on the greater improvement of SCORAD values in this group. PMID- 20307703 TI - Childhood predictors of recurrent abdominal pain in adolescence: A 13-year population-based prospective study. AB - OBJECTIVE: To investigate maternal and child emotional symptoms, physical health problems, and negative life events measured at children's age 18 months and 12 years as potential predictors for self-reported recurrent abdominal pain (RAP) in adolescents (14 years). METHODS: A population-based prospective study conducted at child health clinics (preventive health care) in Norway followed a cohort of 916 mothers with children from children's age 18 months until adolescence. Child self-report was obtained from 12 years of age. Outcome measure was adolescent self-reported RAP. RESULTS: Of 456 adolescents, 58 (13%) reported RAP. Of these, 36 (62%) were girls. By multivariate analyses, the following maternal factors predicted RAP in adolescence: psychological distress at children's age 18 months (OR, 2.5; 95% CI, 1.3-4.8) and a maternal history of psychological distress at children's age 12 years (OR, 3.2; 95% CI, 1.7-6.2). The following child factors measured at age 12 years predicted RAP in adolescence: abdominal (OR, 2.5; 95% CI, 1.3-4.9) and extraintestinal pain (OR, 2.3; 95% CI, 1.2-4.4) by maternal report, self-reported frequent extraintestinal pain (OR, 2.9; 95% CI, 1.4-5.9), and self-reported depressive symptoms (OR, 2.4; 95% CI, 1.1-5.1). Negative life events and physical health in mothers and toddlers did not predict RAP. CONCLUSIONS: This is the first cohort study that finds maternal psychological distress in early childhood to predict RAP in their offspring 13 years later. Our results support that maternal psychological distress and preadolescent children's depressive and somatic symptoms may play a role in the development of RAP. PMID- 20307704 TI - Is fear of pain related to placebo analgesia? AB - OBJECTIVE: Verbal information that a painkiller has been administered generates an expectation of pain relief which in turn decreases pain. This expectation based pain reduction is termed placebo analgesia. We hypothesized that fear of pain would be related to higher stress and pain intensity and to reduced placebo analgesia. METHODS: Sixty-three students (30 females) participated in a Two Condition (placebo, natural history)xFive-Test (one pretest, four post-tests) within-subjects design. Heat pain was induced by a 30x30-mm contact thermode to the medial volar forearm. Each pain test lasted for 4 min at a temperature of 46 degrees C. Stress, arousal, and pain intensity and pain unpleasantness were rated on 100-mm visual analogue scales. RESULTS: Fear of pain was related to higher anticipatory stress and to higher stress and pain intensity during pain. Fear of pain was also related to reduced placebo analgesic responding. CONCLUSION: Fear of pain was positively related to stress both during pain and in the anticipation of pain, and negatively related to placebo analgesia. Previous research has indicated a role for increased stress in the nocebo response, and the present findings suggest that decreased stress may strengthen the placebo response. PMID- 20307705 TI - Biopsychosocial impact of the voice in relation to the psychological features in female student teachers. AB - OBJECTIVE: The aim of the study was to assess biopsychosocial impact of the voice in relation to the psychological features in female student teachers. METHODS: This research was a cross-sectional study in 755 student teachers using general questionnaires, the Voice Handicap Inventory (VHI), Type D Scale-16, Symptom Check List (SCL-90), and Utrecht Coping List (UCL). Student teachers with a relative high score on the VHI (>75th percentile) and students with a relative low score (<25th percentile) were compared. RESULTS: Type D student teachers had a 4x greater risk of a high VHI-score (OR 4.23) than the non-type-D group. The student teachers with relative high VHI scores scored significantly higher (P<.001) on the SCL-90 total and all subscales, compared to the student teachers with relative low VHI scores. Furthermore, the students with a relative high VHI score had significant high scores on the subscales passive attitude (P<.001), palliative reactions (P<.001), avoidance and a waiting attitude (P<.001), and expression of emotions (P=.003) of the UCL. CONCLUSION: This study showed that a relative high biopsychosocial impact of the voice is related to the personality trait Type D, psychosomatic well-being and coping strategies in female student teachers. These features should be implemented in screening and training programs for students for a voice demanding profession. The students have to be prepared to cope with psychological, physical and vocal demands of the teaching profession. The speech therapist (of the vocational university) has to be aware of an important role in coaching the students into a more active coping attitude. PMID- 20307706 TI - Predictors of treatment outcome after cognitive behavior therapy and antispasmodic treatment for patients with irritable bowel syndrome in primary care. AB - OBJECTIVE: To examine predictors of treatment outcome in IBS-patients who participated in a randomized controlled trial in primary care, where 149 irritable bowel syndrome (IBS) patients were randomized to mebeverine hydrochloride (n=77) or mebeverine+cognitive behavior therapy (CBT) (n=72). CBT offered additional benefit over mebeverine alone. METHODS: Regression analyses were used to identify predictors of work and social adjustment 12 months after treatment ended. The intervention groups were analyzed separately in order to look at the separate effects in each group. RESULTS: Lower levels of psychological distress (anxiety and depression) at baseline predicted a good outcome in the mebeverine group [beta=0.388 (95% CI: 0.065-0.936), P=.025] but not in the mebeverine+CBT group. In the adjusted model for the mebeverine+CBT group less adaptive IBS related behavioral coping predicted a good outcome [beta=0.285 (95% CI: 0.002-0.210), P=.045]. CONCLUSION: Different factors are associated with outcome depending on the treatment received. At assessment clinicians should assess patients coping styles and may want to consider recommending CBT to those patients with IBS in primary care who are engaging in unhelpful coping behavior. PMID- 20307707 TI - Biopsychosocial research revisited. PMID- 20307710 TI - Stem cell source and outcome after hematopoietic stem cell transplantation (HSCT) in children and adolescents with acute leukemia. AB - Allogeneic hematopoietic stem cell transplantation from siblings, unrelated donors or HLA mismatched family members has become an important procedure to offer a chance of cure to children and adolescents with acute leukemia at high risk of relapse and those with certain genetic diseases. Bone marrow (BM) was the only stem cell source for many years. During the past 15 years, peripheral blood stem cells from granulocyte colony-stimulating factor (G-CSF) mobilized healthy donors, or umbilical cord blood from related or unrelated donors, have become available. Each stem cell source has different risks/benefits for patients and donors, the choice depending not only on availability, but also on HLA compatibility and urgency of the HSCT. This review will analyze the advantages and limitations of each of these options, and the main criteria which can be applied when choosing the appropriate stem cell source for pediatric transplant recipients with acute leukemia. PMID- 20307709 TI - Hematopoietic stem cell transplantation for leukemia. AB - Leukemia represents the most common pediatric malignancy, accounting for approximately 30% of all cancers in children less than 20 years of age. Most children diagnosed with leukemia are cured without hematopoietic stem cell transplantation (HSCT), but for some high-risk subgroups, allogeneic HSCT plays an important role in their therapeutic approach. The characteristics of these high-risk subgroups and the role of HSCT in childhood leukemias are discussed. PMID- 20307712 TI - The graft-versus-tumor effect in pediatric malignancy. AB - Because severe forms of the graft-versus-host reaction directed against normal tissues (also termed graft-versus-host disease [GVHD]) also contribute to morbidity and mortality following allogeneic hematopoietic stem cell transplantation, major efforts have focused on strategies to separate GVHD from the potentially beneficial immune reactivity against tumor (also called the graft versus-tumor [GVT] effect). This article focuses on the data supporting the contribution of the GVT effect to cure of malignancy, what is known about the biology of the GVT reaction, and, finally, strategies to manipulate the GVT effect to increase the potency of HSCT. PMID- 20307711 TI - Autologous and allogeneic cellular therapies for high-risk pediatric solid tumors. AB - Since the 1950s, the overall survival of children with cancer has gone from almost zero to approaching 80%. Although there have been notable successes in treating solid tumors such as Wilms tumor, some childhood solid tumors have continued to elude effective therapy. With the use of megatherapy techniques such as tandem transplantation, dose escalation has been pushed to the edge of dose limiting toxicities, and any further improvements in event-free survival will have to be achieved through novel therapeutic approaches. This article reviews the status of autologous and allogeneic hematopoietic stem cell transplantation (HSCT) for many pediatric solid tumor types. Most of the clinical experience in transplant for pediatric solid tumors is in the autologous setting, so some general principles of autologous HSCT are reviewed. The article then examines HSCT for diseases such as Hodgkin disease, Ewing sarcoma, and neuroblastoma, and the future of cell-based therapies by considering some experimental approaches to cell therapies. PMID- 20307714 TI - Immunotherapy in the context of hematopoietic stem cell transplantation: the emerging role of natural killer cells and mesenchymal stromal cells. AB - Immunotherapy in the context of hematopoietic stem cell transplantation has been dominated for many years by T-cell- and dendritic-cell-based treatment modalities. During the last decade, insight into the biology of natural killer (NK) cells and mesenchymal stromal cells (MSC) has rapidly increased and resulted in NK- and MSC-based therapeutic strategies in clinical practice. This article reviews current knowledge of the biology and clinical aspects of NK cells and MSC. PMID- 20307713 TI - T-cell-based therapies for malignancy and infection in childhood. AB - One major advance in T-cell-based immunotherapy in the last 20 years has been the molecular definition of numerous viral and tumor antigens. Adoptive T-cell transfer has shown definite clinical benefit in the prophylaxis and treatment of viral infections that develop in pediatric patients after allogeneic transplant and in posttransplant lymphoproliferative disease associated with the Epstein Barr virus. Developing adoptive T-cell therapies for other malignancies presents additional challenges. This article describes the recent advances in T-cell-based therapies for malignancy and infection in childhood and strategies to enhance the effector functions of T cells and optimize the cellular product, including gene modification and modulation of the host environment. PMID- 20307715 TI - Current international perspectives on hematopoietic stem cell transplantation for inherited metabolic disorders. AB - Inherited metabolic disorders (IMD) or inborn errors of metabolism are a diverse group of diseases arising from genetic defects in lysosomal enzymes or peroxisomal function. These diseases are characterized by devastating systemic processes affecting neurologic and cognitive function, growth and development, and cardiopulmonary status. Onset in infancy or early childhood is typically accompanied by rapid deterioration. Early death is a common outcome. Timely diagnosis and immediate referral to an IMD specialist are essential steps in management of these disorders. Treatment recommendations are based on the disorder, its phenotype including age at onset and rate of progression, severity of clinical signs and symptoms, family values and expectations, and the risks and benefits associated with available therapies such as allogeneic hematopoietic stem cell transplantation (HSCT). This review discusses indications for HSCT and outcomes of HSCT for selected IMD. An international perspective on progress, limitations, and future directions in the field is provided. PMID- 20307716 TI - Bone marrow transplantation for inherited bone marrow failure syndromes. AB - The inherited bone marrow failure (BMF) syndromes are characterized by impaired hematopoiesis and cancer predisposition. Most inherited BMF syndromes are also associated with a range of congenital anomalies. Progress in improving the outcomes for children with inherited BMF syndromes has been limited by the rarity of these disorders, as well as disease-specific genetic, molecular, cellular, and clinical characteristics that increase the risks of complications associated with hematopoietic stem cell transplantation (HSCT). As a result, the ability to develop innovative transplant approaches to circumvent these problems has been limited. Recent progress has been made, as best evidenced in studies adding fludarabine to the preparative regimen for children undergoing unrelated donor HSCT for Fanconi anemia. The rarity of these diseases coupled with the far more likely incremental improvements that will result from ongoing research will require prospective international clinical trials to improve the outcome for these children. PMID- 20307717 TI - Hematopoietic stem cell transplantation for osteopetrosis. AB - Osteopetrosis is the generic name for a group of diseases caused by deficient formation or function of osteoclasts, inherited in either autosomal recessive or dominant fashion. Osteopetrosis varies in severity from a disease that may kill infants to an incidental radiological finding in adults. It is increasingly clear that prognosis is governed by which gene is affected, making detailed elucidation of the cause of the disease a critical component of optimal care, including the decision on whether hematopoietic stem cell transplantation is appropriate. This article reviews the characteristics and management of osteopetrosis. PMID- 20307718 TI - Hematopoietic stem cell transplantation for hemoglobinopathies: current practice and emerging trends. AB - Despite improvements in the management of thalassemia major and sickle cell disease, treatment complications are frequent and life expectancy remains diminished for these patients. Hematopoietic stem cell transplantation (HSCT) is the only curative option currently available. Existing results for HSCT in patients with hemoglobinopathy are excellent and still improving. New conditioning regimens are being used to reduce treatment-related toxicity and new donor pools accessed to increase the number of patients who can undergo HSCT. PMID- 20307719 TI - Bone marrow transplantation for primary immunodeficiency diseases. AB - Advances in immunology have led to a breathtaking expansion of recognized primary immunodeficiency diseases (PID) with over 120 disease-related genes identified. In North America alone more than 1000 children have received allogeneic blood or marrow transplant over the past 30 years, with the majority surviving long term. This review presents results and highlights challenges and notable advances, including novel less toxic conditioning regimens, to transplant the more common and severe forms of PID. HLA-matched sibling donors remain the ideal option, however, advances in living donor unrelated HSCT and banked umbilical cord blood grafts provide hope for all children with severe PID. PMID- 20307720 TI - Autologous hematopoietic stem cell transplantation for childhood autoimmune disease. AB - Autologous and allogeneic hematopoietic stem cell transplantation (HSCT) can be used in the management of patients with autoimmune disorders. Experience gained in adults has helped to better define the conditioning regimens required and appropriate selection of patients who are most likely to benefit from autologous HSCT. The field has been shifting toward the use of safer and less intense nonmyeloablative regimens used earlier in the disease course before patients accumulate extensive irreversible organ damage. This article reviews the experience of using autologous HSCT in treating the most common childhood autoimmune and rheumatic diseases, primarily juvenile idiopathic arthritis, systemic lupus erythematosus, and diabetes mellitus. PMID- 20307721 TI - Management of acute graft-versus-host disease in children. AB - Acute graft-versus-host disease (aGVHD) remains a major cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation (HSCT) in children. Although 30% to 50% of children respond to corticosteroids as initial therapy, the optimal initial or second-line therapies have not yet been determined. Newer approaches with combination therapy, novel agents, monoclonal antibodies, and/or cellular therapies show some promise but require prospective well-designed trials that include children to establish their efficacy. This article reviews the clinical presentation, treatment, and practical management guidelines for children with aGVHD. PMID- 20307723 TI - The burden of cure: long-term side effects following hematopoietic stem cell transplantation (HSCT) in children. AB - Children who survive hematopoietic stem cell transplantation (HSCT) are at risk for an inordinate number of long-term side effects. Late effects can be secondary to the underlying diagnosis for which the transplant is performed, prior treatment of the disease, the transplant preparative regimen, treatment of the complications of transplant, and immunologic interactions between the graft and the host. This article describes the risks and manifestations of the most commonly reported late effects in survivors of pediatric HSCT. PMID- 20307724 TI - Opportunities for the prevention of osteoarthritis. PMID- 20307725 TI - A National Public Health Agenda for Osteoarthritis 2010. PMID- 20307722 TI - Chronic graft-versus-host disease (GVHD) in children. AB - Five-year survival rates for childhood cancer now exceed 80% and with the significant progress made by the transplant community in developing less toxic conditioning regimens and in the treatment of posttransplant complications, allo hematopoietic stem cell transplantation (HSCT) contributes significantly to that population of long-term survivors. In this context, the acute and long-term toxicities of chronic graft-versus-host disease (cGVHD) have an ever-increasing effect on organ function, quality of life, and survival; patients and families who initially felt great relief to be cured from the primary disease, now face the challenge of a chronic debilitating illness for which preventative and treatment strategies are suboptimal. Hence, the development of novel strategies that reduce and or control cGVHD, preserve graft-versus-tumor effects, facilitate engraftment and immune reconstitution, and enhance survival after allo-HSCT represents one of the most significant challenges facing physician-scientists and patients. PMID- 20307727 TI - Expression of Toll-like receptor 2 and 4 in inflamed pulp in severe combined immunodeficiency (SCID) mice. PMID- 20307729 TI - Antibacterial efficacy of MTAD final rinse and two percent chlorhexidine gel medication in teeth with apical periodontitis. PMID- 20307730 TI - Anesthetic efficacy of 1.8 milliliters and 3.6 milliliters of 2% lidocaine with 1:100,000 epinephrine for posterior superior alveolar nerve blocks. AB - INTRODUCTION: The purpose of this prospective, randomized, single-blinded study was to measure the degree of anesthesia obtained with 1.8 mL and 3.6 mL of 2% lidocaine with 1:100,000 epinephrine in posterior superior alveolar (PSA) nerve blocks. METHODS: Thirty-one adult subjects randomly received PSA nerve blocks of 1.8 mL and 3.6 mL of the lidocaine solution at 2 separate appointments in a crossover design. An electric pulp tester was used to test for anesthesia of the first and second molars and premolars in 3-minute cycles for 50 minutes. Anesthesia was considered successful when 2 consecutive 80 readings were obtained within 15 minutes. RESULTS AND CONCLUSIONS: Anesthetic success for the 1.8 mL volume of 2% lidocaine with 1:100,000 epinephrine was 97% for the second molar and 77% for the first molar. Anesthetic success for the 3.6 mL volume of 2% lidocaine with 1:100,000 epinephrine was 100% for the second molar and 84% for the first molar. The differences were not statistically significant between the 2 anesthetic volumes. Anesthetic success for the premolars for both volumes was in the low to moderate range and would not provide predictable pulpal anesthesia. For the first molar, the 3.6 mL volume of the lidocaine formulation provided a statistically longer duration of pulpal anesthesia than the 1.8 mL volume. The pain of depositing a 3.6 mL volume of a lidocaine solution was not statistically more painful than depositing a 1.8 mL volume. PMID- 20307731 TI - A systematic evaluation of the quality of meta-analyses in endodontics. AB - INTRODUCTION: Meta-analyses have been suggested to be the highest form of evidence available to clinicians to guide clinical practice in dental care. High methodologic quality is a prerequisite for valid interpretation and application of review findings. However, meta-analyses are complex exercises, and assessing quality can be a daunting task. Clinicians and policymakers require guidance, which is not provided adequately by the available literature on the quality of meta-analyses. The purpose of this study was to systematically evaluate the quality of meta-analyses that address topics pertinent to endodontics. METHODS: To identify potentially eligible meta-analyses for inclusion, systematic searches performed in MEDLINE and the Cochrane Database of Systematic Reviews were enriched by hand searches, citation mining, and expert recommendation. Comprehensive search strategies were constructed for electronic searches. Predetermined inclusion criteria were applied to each identified meta-analysis independently by two reviewers. To assess report quality, the included meta analyses were assessed by using A Measurement Tool to Assess Systematic Reviews (AMSTAR). RESULTS: A total of 16 reports of meta-analyses were included (kappa = 0.96). The overall quality of reports of meta-analyses was found to be high, with an estimated mean overall AMSTAR score of 8.33 out of 11 (95% confidence interval, 7.62-8.88). The weakest areas within the included meta-analyses were failure to report the likelihood of publication bias. CONCLUSIONS: The overall quality of the reports of meta-analyses available in endodontics is high according to AMSTAR. PMID- 20307732 TI - Identifying and reducing risks for potential fractures in endodontically treated teeth. AB - INTRODUCTION: Although long-term functional survival rates can be high for initial endodontically treated permanent teeth, they are generally more susceptible to fracture than teeth with vital pulps. Tooth extraction is often the consequence of an unfavorable prognosis after coronal and root fractures, but their occurrence in endodontically treated teeth might be reduced by identifying the risks for fracture associated with various operative procedures. METHODS: This article presents an overview of the risk factors for potential tooth fractures in endodontically treated teeth on the basis of literature retrieved from PubMed and selected journal searches. RESULTS: Postendodontic tooth fractures might occur because of the loss of tooth structure and induced stresses caused by endodontic and restorative procedures such as access cavity preparation, instrumentation and irrigation of the root canal, obturation of the instrumented root canal, post-space preparation, post selection, and coronal restoration and from inappropriate selection of tooth abutments for prostheses. CONCLUSIONS: Potential tooth fractures might be reduced by practitioners being aware during dental treatments of controllable and noncontrollable risks. PMID- 20307733 TI - Guided tissue regeneration in periapical surgery. AB - Tissue regeneration by using membrane barriers and bone grafting materials in periapical surgery is an example of tissue engineering technology. Membrane barriers and/or bone grafts are often used to enhance periapical new bone formation. However, the periapical tissues also consist of the periodontal ligament (PDL) and cementum. For regeneration of the periapical tissues after periapical surgery, one of the important requirements is recruitment and differentiation of progenitor/stem cells into committed pre-osteoblasts, pre-PDL cells, and pre-cementoblasts. Homing of progenitor/stem cells into the wounded periapical tissues is regulated by factors such as stromal cell-derived factor 1, growth factors/cytokines, and by microenvironmental cues such as adhesion molecules and extracellular matrix and associated noncollagenous molecules. Tissue regeneration after injury appears to recapitulate the pathway of normal embryonic tissue development. Multiple tissue regeneration involves a complex interaction between different cells, extracellular matrix, growth/differentiation factors, and microenvironmental cues. Little is known concerning the biologic mechanisms that regulate temporal and spatial relationship between alveolar bone, PDL, and cementum regeneration during periapical wound healing. Simply applying a membrane barrier and/or bone graft during periapical surgery might not result in complete regeneration of the periapical tissues. It has not been clearly demonstrated that these biomaterials are capable of recruiting progenitor/stem cells and inducing these undifferentiated mesenchymal cells to differentiate into PDL cells and cementoblasts after periapical surgery. PMID- 20307734 TI - Isolation and taxonomy of filamentous fungi in endodontic infections. AB - INTRODUCTION: The purpose of this study was to research the presence of filamentous fungi in the root canals of teeth with pulp necrosis and periapical lesions and to perform the taxonomic study of the isolates. METHODS: Samples collected from 60 root canals with sterile absorbent paper points were inoculated in Sabouraud dextrose agar supplemented with chloramphenicol. The material was cultured from 7-14 days at room temperature to observe mycelial growth. Samples with growth were seeded in media specific for microculture (CYA agar, malt extract agar, or potato dextrose agar). Taxonomy was evaluated by macroscopic examination and optical microscopy. RESULTS: Filamentous fungi were isolated in situ from 17 of 60 samples (28.3%). Considering the positive root canal isolates, the genus Aspergillus was isolated from 7 samples (41%); 4 species were identified: Aspergillus ustus, A. granulosus, A. niger, and A. sydowii. Emericella quadriluniata, sexual form of Aspergillus, was isolated from 1 sample. Penicillium species (Penicillium implicatum, P. micsynvisk, P. lividum, and P. citrionigrum) were isolated from 4 samples (24%). Fusarium species (Fusarium moniliforme and F. melanochorum) were isolated from 2 samples (12%). The species Aureobasidium pullulans, Exophiala jeanselmei, Eurotium amstelodame, and Cladosporium sphaerospermum were isolated from 1 sample each. CONCLUSIONS: The root canals of teeth with pulp necrosis and periapical lesions might present positive culture for filamentous fungi. PMID- 20307735 TI - Biofilm formation capability of Enterococcus faecalis cells in starvation phase and its susceptibility to sodium hypochlorite. AB - INTRODUCTION: Enterococcus faecalis is commonly associated with persistent periapical infections. The physiologic state of the cells in the canal is probably closest to the starvation state. However, the biofilm formation capability of starved E. faecalis cells on human dentin and the susceptibility of the biofilm to 5.25% sodium hypochlorite remain poorly understood. METHODS: E. faecalis American Type Culture Collection (ATCC) 29212 in different growth phases were incubated on human dentin and polystyrene blocks. Scanning electron microscopy and biofilm assay were used to investigate the biofilm formation capability of these cells. The susceptibility of the biofilm to 5.25% NaClO was also determined by the plate count method. RESULTS: Scanning electron microscopy and biofilm assay showed that starved cells were able to form biofilm on dentin with reduced efficiency as compared with the cells in the exponential phase and stationary phase (p < 0.05). Biofilm grown on dentin harbored more cells than polystyrene (p < 0.05). Biofilms of starved cells were more resistant to 5.25% NaClO than those of stationary cells (p < 0.05), and the impact of 5.25%NaClO on them decreased as the biofilm matured. CONCLUSION: E. faecalis cells in the starvation phase could develop biofilm on human dentin, which is responsive to 5.25% NaClO. It may contribute to the predominant role of E. faecalis involved in persistent periapical infections. PMID- 20307736 TI - Effect of cytosolic phospholipase A2 on proinflammatory cytokine-induced bone resorptive genes including receptor activator of nuclear factor kappa B ligand in human dental pulp cells. AB - INTRODUCTION: Although cytokines stimulate prostaglandin E(2) (PGE(2)) production and cyclooxygenase-2 (COX-2) gene expression in human dental pulp cells (HDPCs), the involvement of cytosolic phospholipase A(2) (cPLA(2)) has not been assessed. The purpose of this study was to examine the role of cPLA(2) on the regulation of proinflammatory cytokine-stimulated genes associated with osteoclast differentiation or bone resorption. METHODS: Tumor necrosis factor-alpha (TNF alpha) and interleukin-1alpha (IL-1alpha)-induced COX-2 and receptor activator of nuclear factor kappa B ligand (RANKL) mRNA and protein expression in the HDPCs was determined by using reverse transcription-polymerase chain reaction (RT-PCR) and Western blot analysis. PGE(2) release and osteoclast-related gene expression were measured by enzyme-linked immunosorbent assay and RT-PCR. RESULTS: Stimulation with TNF-alpha and IL-1alpha synergistically increased levels of COX 2 as well as RANKL mRNA and protein expression. Osteoclast markers (macrophage colony-stimulating factor [M-CSF], matrix metalloproteinase-9 [MMP-9], and tartrate-resistant acid phosphatase [TRAP]) and osteolysis regulating cytokines or osteoclastogenic cytokines (IL-6, IL-11, and Il-17) were up-regulated in HDPCs after IL-1alpha and TNF-alpha treatment. A cPLA(2) inhibitor attenuated both the cytokine-stimulated PGE(2) release as well as changes in osteoclast differentiation-related genes like RANKL. CONCLUSIONS: These results suggest that cPLA(2) is involved in inflammatory cytokine-induced osteoclastogenic gene expression and consequent damage or destruction. PMID- 20307737 TI - Methylation pattern of the IFN-gamma gene in human dental pulp. AB - INTRODUCTION: DNA methylation is characterized by the addition of methyl groups in cytosines within cytosine-phosphate-guanine (CpG) islands. Unmethylated islands are related with transcriptionally active structure, whereas methylated DNA recruits methyl-binding proteins that promotes chromatin compaction. Although epigenetic events can influence the expression of cytokines, such events have not been investigated in dental pulp yet. The purpose of the present study was to evaluate the methylation status of the interferon gamma (IFN-gamma) gene in human dental pulp affected by inflammation compared with pulp tissue of impacted molar teeth and to verify the impact of methylation status in the expression pattern of the gene. METHODS: Methylation-specific polymerase chain reaction (MSP) was used to verify the DNA methylation status of the IFN-gamma gene in 16 human dental pulps affected by inflammation and in 16 pulp samples of impacted molar teeth. Histologic sections stained by hematoxylin-eosin were used for histopathological evaluation, and the expression of IFN-gamma was assessed by quantitative real time PCR (qPCR). RESULTS: Although total methylation was observed in 43.75% of the samples of normal dental pulp tissues, partial methylation or unmethylation was found in 93.75% of the samples of inflamed pulp tissues. All the samples with total methylation in MSP showed no transcription of IFN-gamma. The qPCR results showed expression of IFN-gamma in 5 of 10 samples with partial methylation. CONCLUSION: The present study gives the first evidence of the possible participation of epigenetic events in the development of dental pulp inflammation. PMID- 20307738 TI - Mineral trioxide aggregate induces bone morphogenetic protein-2 expression and calcification in human periodontal ligament cells. AB - INTRODUCTION: Mineral trioxide aggregate (MTA) is a therapeutic, endodontic repair material that is reported to exhibit calcified tissue-conductive activity although the mechanisms remain unclear. We hypothesize that the dissolution of calcium from MTA into the surrounding environment may play an important role in the osteoblastic/cementoblastic differentiation of human periodontal ligament cells (HPLCs). METHODS: Two populations of HPLCs were obtained from two patients, respectively, and were cultured in the presence or absence of MTA discs and/or CaCl(2) in order to investigate calcium release, calcification activity, calcium sensing receptor (CaSR) gene expression and bone morphogenetic protein-2 (BMP-2), and BMP-2 receptor protein and gene expression. RESULTS: MTA released a substantial accumulation of calcium (4 mmol/L) within 14 days into culture media. After 4 weeks, the two populations of HPLCs independently exhibited calcification as well as BMP-2 distribution in the vicinity of MTA. HPLCs inherently expressed genes encoding for the CaSR and BMP-2 receptors. Exogenous CaCl(2) media supplementation induced CaSR gene expression in HPLCs and calcification and BMP-2 synthesis throughout the entire HPLC cultures, whereas MgCl(2) had no effect. Both MTA and CaCl(2) stimulated BMP-2 gene expression above that of baseline levels. CONCLUSION: Here we show the first report showing that HPLCs cocultured directly with MTA up-regulated BMP2 expression and calcification. These results may be through CaSR interactions that were potentially activated by the release of calcium from MTA into the culture environment. PMID- 20307739 TI - The prevalence and morphologic classification of distolingual roots in the mandibular molars in a Korean population. AB - INTRODUCTION: The aims of this study were to determine the incidence and concurrency rate of distolingual (DL) roots on mandibular molars and to classify them according to their morphologic features. METHODS: Serial cross-sectional computed tomography images of the mandibles were collected retrospectively from 1,775 Korean patients of Mongoloid origin. The incidence of DL roots was calculated for each molar, and their patterns of concurrence were analyzed with the Fisher exact test. DL roots were categorized into five groups according to their morphologic characteristics using the three-dimensional reconstructed images. RESULTS: The incidence rate of DL roots was highest for first molars (24.5%) and lowest for second molars (0.7%). They were often present concurrently in adjacent molars (p < 0.004). The morphologic characteristics of DL roots in the first molars varied greatly from a severely curved type (type III, 40.5%) to an underdeveloped small type or a conical type (2.5% and 1.4%, respectively). CONCLUSION: Data regarding the pattern of occurrence and the morphologic features of DL roots can provide useful information to clinicians, leading to higher rate of success of endodontic treatment. PMID- 20307740 TI - Protective effects of follicle-stimulating hormone inhibitor on alveolar bone loss resulting from experimental periapical lesions in ovariectomized rats. AB - INTRODUCTION: The direct effect of follicle-stimulating hormone (FSH) on bone resorption has been demonstrated recently. The aim of this study was to evaluate the effect of FSH inhibitor leuprorelin (LE) on alveolar bone loss resulting from experimental periapical lesions in ovariectomized (OVX) rats. METHODS: Twenty seven female rats were randomly assigned into 4 groups and subjected to ovariectomy or sham surgery (1.6 mg/kg body weight LE or vehicle was injected immediately). One week after surgery, the pulp of each rat's bilateral lower first molars was exposed to the oral environment. Three weeks after pulpal exposure, all the animals were killed, and bilateral mandibles were extracted for histologic processing. Radiographic and histologic examination for periapical bone loss area, enzyme histochemical examination for tartrate-resistant acid phosphatase (TRAP), and immunohistochemical examination for FSH receptor (FSHR) were performed. RESULTS: LE significantly decreased the alveolar bone loss area and osteoclast occurrence compared with non-LE treatment ovariectomized rats (P < .05), and the number of FSHR-positive cells was significantly correlated with alveolar bone loss area (r = 0.796, P < .01). CONCLUSIONS: LE has protective effects on alveolar bone loss resulting from experimental periapical lesions in OVX rats. PMID- 20307741 TI - Morphologic analysis of the root apex in human teeth. AB - INTRODUCTION: To determine the morphologic shape and position of the root apex and the major foramen in maxillary and mandibular teeth. METHODS: A total of 845 maxillary and mandibular human teeth root specimens were evaluated. Each root specimen was measured at each root apex by using a calibrated microscope at a magnification of 20x. The anatomic parameters evaluated included the position of the root apex and the major foramen (in the center, buccal, lingual, mesial, or distal) and shapes of peripheral contours of the major foramen (rounded, oval, asymmetric, and semilunar) and root apex (rounded, flat, beveled, and elliptical). All data were summarized, and means, frequencies, and percentages were calculated for each group of specimens (incisors, canines, premolars, and molars). RESULTS: The most frequent root apex morphology in maxillary and mandibular teeth was the round shape (35.1%). The most frequent shape of the apical foramen was round (52.9%) or oval (25.2%). The major location of both the root apex (39.7%) and the major foramen (58.4%) was in the center of the root. CONCLUSION: The most frequent root apex morphology and apical foramen in the maxillary and mandibular teeth was the round followed by the oval shape. The most prevalent location of the root apex and the major foramen was in the center followed by the distal position. PMID- 20307742 TI - Ca2+ extrusion via Na+-Ca2+ exchangers in rat odontoblasts. AB - INTRODUCTION: Intracellular Ca(2+) is essential to many signal transduction pathways, and its level is tightly regulated by the Ca(2+) extrusion system in the plasma membrane, which includes the Na(+)-Ca(2+) exchanger (NCX). Although expression of NCX1 isoforms has been demonstrated in odontoblasts, the detailed properties of NCX remain to be clarified. In this study, we investigated localization and ion-transporting/pharmacologic properties of NCX isoforms in rat odontoblasts. METHODS: We characterized both the reverse and forward modes of NCX activity in odontoblasts in a dental pulp slice preparation. Ca(2+) influx by reverse NCX activity was measured by fura-2 fluorescence. Ca(2+) efflux by forward NCX activity elicited inward Na(+) current as measured by perforated patch clamp recording. For immunohistochemical analysis, cryostat sections of incisors were incubated with antibodies against NCX. RESULTS: Immunohistochemical observation revealed localization of NCX1 and NCX3 in the distal membrane of odontoblasts. Inward currents by forward NCX activity showed dependence on external Na(+). Fura-2 fluorescence measurement revealed that Ca(2+) influx by reverse NCX activity depended on extracellular Ca(2+) concentration, and that this influx was blocked by NCX inhibitor KB-R7943 in a concentration-dependent manner. However, Ca(2+) influx by NCX showed a slight sensitivity to SEA0400 (a potent NCX1 inhibitor), indicating that expression potencies in odontoblasts were NCX3 > NCX1. CONCLUSIONS: These results suggest that odontoblasts express NCX1 and NCX3 at the distal membrane, and that these isoforms play an important role in the Ca(2+) extrusion system as well as in the directional Ca(2+) transport pathway from the circulation to the dentin-mineralizing front. PMID- 20307743 TI - Antifungal efficacy of 5.25% sodium hypochlorite, 2% chlorhexidine gluconate, and 17% EDTA with and without an antifungal agent. AB - INTRODUCTION: The aim of this in vitro study was to evaluate the efficacy of 5.25% sodium hypochlorite (NaOCl), 2% chlorhexidine gluconate (CHX), and 17% EDTA as a final irrigant with and without the inclusion of an antifungal agent (1% clotrimazole) on Candida albicans. METHODS: Sixty-five single-rooted instrumented and inoculated with a suspension of C. albicans. The experimental specimens were divided into two groups. The irrigant group was divided into three subgroups and irrigated with 5.25% NaOCl, 2% CHX, and 17% EDTA, respectively. The irrigant with antifungal group was divided into three subgroups and irrigated with 5.25% NaOCl, 2% CHX, and 17% EDTA respectively followed by 1% clotrimazole. Aliquots from the experimental teeth were plated on 4% Sabouraud agar (Tital Biotech, Delhi, India), and the colony-forming units (CFUs) were evaluated under light microscopy (400x). RESULTS: NaOCl, 5.25%, exhibited superior antifungal efficacy compared with 2% CHX and 17% EDTA (p < 0.001). On inclusion of 1% clotrimazole, there was a significant decrease in the CFU (p < 0.001); 5.25% NaOCl and 2% CHX with clotrimazole showed significantly greater antifungal properties than 17% EDTA with clotrimazole (p < 0.001). CONCLUSION: One percent of clotrimazole proved to be effective against C. albicans when used along with root canal irrigants as a final rinse. PMID- 20307744 TI - The self-adjusting file (SAF). Part 1: respecting the root canal anatomy--a new concept of endodontic files and its implementation. AB - AIM: To introduce a new concept, the self-adjusting file (SAF), and discuss its unique features compared with current rotary nickel-titanium file systems. THE NEW CONCEPT: The SAF file is hollow and designed as a thin cylindrical nickel titanium lattice that adapts to the cross-section of the root canal. A single file is used throughout the procedure. It is inserted into a path initially prepared by a # 20 K-file and operated with a transline- (in-and-out) vibration. The resulting circumferential pressure allows the file's abrasive surface to gradually remove a thin uniform hard-tissue layer from the entire root canal surface, resulting in a canal with a similar cross-section but of larger dimensions. This holds also for canals with an oval or flat cross-section, which will be enlarged to a flat or oval cross-section of larger dimensions. The straightening of curved canals is also reduced because of the high pliability of the file and the absence of a rigid metal core. Thus, the original shape of the root canal is respected both longitudinally and in cross-section. The hollow SAF file is operated with a constant flow of irrigant that enters the full length of the canal and that is activated by the vibration and is replaced continuously throughout the procedure. This results in effective cleaning even at the cul de sac apical part of the canal. The SAF has high mechanical endurance; file separation does not occur; and mechanical failure, if it occurs, is limited to small tears in the latticework. CONCLUSION: The SAF represents a new step forward in endodontic file development that may overcome many of the shortcomings of current rotary nickel-titanium file systems. PMID- 20307745 TI - The self-adjusting file (SAF). Part 2: mechanical analysis. AB - INTRODUCTION: The study was designed to explore the mechanical properties of the self-adjusting file (SAF) and its application in the root canal using continuous irrigation. METHODS: The compressibility of the SAF file and the resulting peripheral force were measured using specially designed systems. The abrasivity of the file was tested on dentin blocks representing a flat root canal. The durability of the SAF file was tested using a functional fatigue-to-failure assay. Degradation of the file was evaluated by using files that were previously used for 10, 20, and 30 minutes and comparing their efficacy with that of new, unused files. The potential of extruding irrigant beyond the apex was explored in roots with an open apical foramen. RESULTS: The SAF file was elastically compressible from a diameter of 1.5 mm to dimensions similar to those of a #20 stainless steel K-file. This compression resulted in an evenly applied force to the root canal walls. The in-and-out vibration of the file and the peripheral force, combined with its abrasivity, allow for hard-tissue removal. Under the conditions of the experiment, no mechanical failure was observed with up to 29 minutes of operation in the root canal. The file loses its efficacy after prolonged use, with a 40% reduction after 30 minutes of operation. The operation of the file with continuous irrigation did not push the irrigant beyond an open apical foramen. CONCLUSIONS: The SAF file is an elastically compressible file that effectively removes dentin and can mechanically endure use under its recommended mode of operation with a minimal loss of efficacy. PMID- 20307746 TI - The self-adjusting file (SAF). Part 3: removal of debris and smear layer-A scanning electron microscope study. AB - AIM: The aim of this study was to evaluate the cleaning ability of the Self Adjusting File (SAF) system in terms of removal of debris and smear layer. METHODOLOGY: Root canal preparations were performed in 20 root canals using an SAF operated with a continuous irrigation device. The glide path was initially established using a size 20 K-file followed by the SAF file that was operated in the root canal via a vibrating motion for a total of 4 minutes. Sodium hypochlorite (3%) and EDTA (17%) were used as continuous irrigants and were alternated every minute during this initial 4-minute period. This was followed by a 30-second rinse using EDTA applied through a nonactivated SAF and a final flush with sodium hypochlorite. The roots were split longitudinally and subjected to scanning electron microscopy (SEM). The presence of debris and a smear layer in the coronal, middle, and apical thirds of the canal were evaluated through the analysis of the SEM images using five-score evaluation systems based on reference photographs. RESULTS: The SAF operation with continuous irrigation, using alternating irrigants, resulted in root canal walls that were free of debris in all thirds of the canal in all (100%) of the samples. In addition, smear layer free surfaces were observed in 100% and 80% of the coronal and middle thirds of the canal, respectively. In the apical third of the canal, smear layer-free surfaces were found in 65% of the root canals. CONCLUSIONS: The operation of the SAF system with continuous irrigation coupled with alternating sodium hypochlorite and EDTA treatment resulted in a clean and mostly smear layer-free dentinal surface in all parts of the root canal. PMID- 20307747 TI - Preparation of oval-shaped root canals in mandibular molars using nickel-titanium rotary instruments: a micro-computed tomography study. AB - INTRODUCTION: This study evaluated the prepared surface areas of oval-shaped canals in distal roots of mandibular molars using four different instrumentation techniques. METHODS: Teeth were prescanned and reconstructed using micro-computed tomography (MCT) scans at low resolution (68 microm). Forty-eight molars with ribbon-shaped/oval distal root canals were selected and randomly assigned to four groups. Distal canals (n = 12 each) were prepared by circumferential filing using Hedstrom files to apical size #40 (group H/CF); with ProTaper nickel-titanium rotaries to finishing file 4 (F4) considering the distal canal as 1 canal (group PT/1); ProTaper to F4 considering buccal and oral aspects of the distal canal as 2 individual canals (group PT/2); ProTaper to F4 in a circumferential filing motion (PT/CF). Before and after shaping, teeth were evaluated using MCT at 34 microm resolution. The percentage of prepared surface was assessed for the full canal length and the apical 4 mm. Statistical analysis was performed using analysis of variance and Bonferroni/Dunn multiple comparisons. RESULTS: Preoperatively, canal anatomy was statistically similar among the groups (p = 0.56). Mean (+/- standard deviation) untreated areas ranged from 59.6% (+/-14.9, group PT/2) to 79.9% (+/-10.3, PT/1) for the total canal length and 65.2% to 74.7% for the apical canal portion, respectively. Canals in group PT/1 had greater untreated surface areas (p < 0.01) than groups PT/2 and PT/CF. Among all groups, amounts of treated surface areas were statistically similar in the apical 4 mm. CONCLUSIONS: Preparations of oval-shaped root canals in mandibular molars left a variable portion of surface area unprepared regardless of the instrumentation technique used. However, considering oval canals as two separate entities during preparation appeared to be beneficial in increasing overall prepared surface. PMID- 20307748 TI - Micro-computed tomographic comparison of nickel-titanium rotary versus traditional instruments in C-shaped root canal system. AB - INTRODUCTION: The purpose of this study was to assess the efficacy of instrumentation of C-shaped canals with ProTaper rotary system and traditional instruments by using micro-computed tomography (micro-CT). METHODS: Twenty-four mandibular molars with C-shaped canals were selected in pairs and sorted equally into 2 groups, which were assigned for instrumentation by ProTaper rotary system (ProTaper group) or by K-files and Gates-Glidden burs (Hand Instrument group). Three-dimensional images were constructed by micro-CT. The volume of dentin removed, uninstrumented canal area, time taken for instrumentation, and iatrogenic error of instrumentation were investigated. RESULTS: Hand Instrument group showed greater amount of volumetric dentin removal and left less uninstrumented canal area than ProTaper group (P < .01). The time needed for instrumentation was shorter for ProTaper group than for Hand Instrument group (P < .05). No instrument breakage occurred in both groups, but more conspicuous procedural errors were detected in Hand Instrument group than for ProTaper group. CONCLUSIONS: It was concluded that ProTaper rotary system maintained the canal curvature with speediness and few procedural errors, whereas traditional instrumentation can clean more canal surface. PMID- 20307749 TI - Influence of water cooling on root surface temperature generated during post space preparation. AB - INTRODUCTION: This in vitro study evaluated the temperature increases on the root surface of teeth during preparation of post space with and without water cooling. METHODS: Thirty premolar teeth with a single canal were used. After root canal obturation, the teeth were divided into 2 groups, and post spaces were prepared by using a drill without cooling (dry group) and with water irrigation of 25 mL/min(-1) (wet group). Temperatures were measured on the entire root surface by using a thermal imaging camera. RESULTS: Root surface temperature increases were significantly lower when post spaces were created with water cooling compared with dry post preparation (P < .0001 for root canal filling removal and P < .0001 for post space preparation). In both groups, significantly higher temperatures were recorded during the post space preparation than during the filling removal (P < .001 for nonirrigated teeth and P < .001 for irrigated teeth). CONCLUSIONS: Irrigation during post space preparation significantly influenced the outer root surface temperature. The risk of irreversible injury to the root surrounding tissues is potentially minimized when post space is prepared by using water cooling. PMID- 20307751 TI - Effect of apical preparation size and preparation taper on irrigant volume delivered by using negative pressure irrigation system. AB - INTRODUCTION: The purpose of this investigation was to determine the effect that apical preparation size and preparation taper had on the volume of irrigant delivered to the working length of a root canal preparation in a clinically relevant amount of time. METHODS: Forty intact human single-rooted teeth were randomly distributed into 2 separate phases. The first phase aimed to determine the smaller apical size that will allow more volume of irrigant at working length. All samples had the same taper and were sequentially instrumented to sizes of 30.06, 35.06, 40.06, and 45.06. The second phase aimed to determine the taper that will allow more volume of irrigant at working length. Teeth were sequentially instrumented to 40.02, 40.04, 40.06, and 40.08. All samples were irrigated by using the micro-cannula, and the volume of sodium hypochlorite suctioned at working length under negative pressure was measured during a period of 30 seconds by using a custom recovery device. RESULTS: An increase in size from ISO #35 to ISO #40 resulted in a percentage gain of approximately 44% in mean irrigant volume, whereas an increase in size from ISO #40 to ISO #45 resulted in a percentage gain of approximately 4%. An increase in taper from 0.02 through 0.08 resulted in percentage gains of approximately 74%, 5.4%, and 2.4% increase, respectively. CONCLUSIONS: The data demonstrated that an increase in apical preparation size and taper resulted in a statistically significant increase in the volume of irrigant. In addition, an apical enlargement to ISO #40 with a 0.04 taper will allow for tooth structure preservation and maximum volume of irrigation at the apical third when using the apical negative pressure irrigation system. PMID- 20307750 TI - Dissolution of nickel-titanium endodontic files via an electrochemical process: a new concept for future retrieval of fractured files in root canals. AB - INTRODUCTION: The retrieval of fractured instruments from root canals has been largely reported in the literature. However, a less complex retrieval method that causes minimum damage to the dental structures is needed. The aim of this article is to introduce a new concept of retrieval of fractured instruments from root canals based on an electrochemical process. METHODS: Current register tests were used to evaluate the dissolution process of 25.04 nickel-titanium (NiTi) K3 rotary files. A constant anodic potential was applied to the NiTi files, whereas the Potentiostat registered the anodic current. After the tests, all files were observed by using an optical microscope. RESULTS: The current attained initial values of approximately 55 mA that declined during the entire test. A good reproducibility of results was observed. The optical microscopy analysis evidenced a progressive consumption of the files with increasing polarization time. CONCLUSIONS: The results presented here show that the concept of fractured file retrieval by an electrochemical process is feasible. This concept resulted in a consistent basis for the development of a method to remove fractured instruments from root canals. PMID- 20307752 TI - Comparison of bacterial reduction in straight and curved canals using erbium, chromium:yttrium-scandium-gallium-garnet laser treatment versus a traditional irrigation technique with sodium hypochlorite. AB - INTRODUCTION: This study compared the reduction of Enterococcus faecalis in straight and curved canals using an erbium, chromium:yttrium-scandium-gallium garnet laser and irrigation with 6.15% sodium hypochlorite (NaOCl). METHODS: Fifty-five single-rooted extracted teeth were divided into straight and curved canal groups. The root lengths were standardized (14.0mm) and NiTi instruments were used to prepare the canals to a size #40/0.06 taper. Irrigation was performed with 6.15% NaOCl and RCPrep (Premier Dental Products Co, Plymouth Meeting, PA) as lubricant. The smear layer was removed with 17% EDTA. The samples were sterilized, inoculated with E. faecalis, and incubated for 48 hours at 37 degrees in a CO(2) chamber. They were then divided into 7 groups: NaOCl in straight canals (NS); NaOCl in curved canals (NC); laser in straight canals (LS); laser in curved canals (LC); positive control straight canals (PCS); positive control curved canals (PCC); and negative control (NegC). Bacterial reduction was measured by counting the colony-forming units (CFUs) and determining the optical density. RESULTS: Groups NS, NC, and LS exhibited bacterial growth in 1 out of 10 samples (10%). In group LC, three out of 10 samples (30%) showed bacterial growth. Kruskal-Wallis showed a statistically significant difference between all treatment groups and the positive controls (p<0.001). Analysis of variance showed a statistical significant difference in optic density between experimental and positive controls. CONCLUSIONS: Traditional irrigation techniques using 6.15% NaOCl effectively eliminated all bacteria in straight and curved canals. Er,Cr:YSGG laser also effectively removed all bacteria from straight canals. However, in three curved canals, even though there were significant bacterial reductions, they failed to render canals completely free of bacteria. PMID- 20307753 TI - Distortion and breakage of Liberator, EndoSequence, and ProFile systems in severely curved roots of molars. AB - INTRODUCTION: The aim of this study was to investigate the incidence of endodontic file distortion and breakage when the Liberator (Miltex Inc, York, PA), EndoSequence (Brasseler USA, Savannah, GA), and ProFile (Tulsa Dental Products, Tulsa, OK) systems were used to instrument severely curved root canals of extracted human molars. METHODS: Eighty-four roots of extracted human molars with curvatures measuring 40 degrees to 80 degrees were used. The roots were randomly assigned into four groups based on the rotary instrumentation system: group 1, ProFile (.04 taper); group 2, EndoSequence (.04 taper); group 3, Liberator (.04 taper); and group 4, Liberator (.02 taper). RESULTS: File distortion was 19.4%, 10%, 44.4%, and 59.1% for the ProFile, EndoSequence, and Liberator .04 and Liberator .02 groups, respectively. There were statistically significant differences between the ProFile and Liberator .04 groups (p < 0.05), the ProFile and Liberator .02 groups (p < 0.01), the EndoSequence and Liberator .04 groups (p < 0.01), and the EndoSequence and Liberator .02 groups (p < 0.01). Broken files occurred in 2.8% of the ProFile group and 7.4% of the Liberator .04 group. There were no broken files in the EndoSequence or Liberator .02 groups. No statistically significant differences were found among the four groups (p = 0.28) with regard to file breakage. CONCLUSION: It can be concluded that more file distortions occurred in both Liberator groups than with either the ProFile or the EndoSequence groups to a statistically significant degree. PMID- 20307754 TI - Effect of final irrigation regimen on sealer penetration in curved root canals. AB - INTRODUCTION: The purpose of this study was to evaluate the effect of different final irrigation regimens on the sealer penetration into dentinal tubules of curved root canals. METHODS: The mesiobuccal canals from 45 extracted maxillary and mandibular molars were instrumented with sodium hypochlorite (NaOCl) irrigation. The samples were divided into 3 groups according to the final irrigation used: group N (control), 3.5% NaOCl; group E, 17% ethylenediaminetetraacetic acid (EDTA); and group EN, 17% EDTA followed by 3.5% NaOCl. All teeth were obturated with gutta-percha and AH Plus sealer labeled with fluorescent dye. Transverse sections at 2 mm (apical) and 5 mm (coronal) from root apex were examined by using confocal laser scanning microscopy. Then, total percentage and maximum depth of sealer penetration were measured. RESULTS: The apical sections in each group showed significantly lower percentage and maximum depth of sealer penetration than the coronal sections (P < .05). In apical levels, group E and EN resulted in a higher percentage of sealer penetration than the control group (P < .05), but there was no significant difference of maximum depth between group E and the control group (P > .05). CONCLUSIONS: In curved canal, final rinse with NaOCl after the use of EDTA had no additional effect on sealer penetration. Complete debridement with a 1-minute application of EDTA remains a challenge in the apical area of curved canals. PMID- 20307755 TI - Study on the influence of refreshment/activation cycles and irrigants on mechanical cleaning efficiency during ultrasonic activation of the irrigant. AB - INTRODUCTION: The aims of this study were to evaluate dentin debris removal from the root canal during ultrasonic activation of sodium hypochlorite (2% and 10%), carbonated water, and distilled water and to determine the influence of 3 ultrasonic refreshment/activation cycles of the irrigant by using the intermittent flush technique. METHODS: Root canals with a standardized groove in 1 canal wall, which was filled with dentin debris, were irrigated ultrasonically. The irrigant was refreshed and ultrasonically activated 3 times for 20 seconds. The quantity of dentin debris after irrigation was determined after each refreshment/activation cycle. RESULTS AND CONCLUSIONS: Ultrasonic activation of the irrigant combined with the intermittent flush method produces a cumulative effect over 3 refreshment/activation cycles. Sodium hypochlorite as an irrigant is significantly more effective than carbonated water, which is significantly more effective than distilled water, in removing dentin debris from the root canal during ultrasonic activation. PMID- 20307756 TI - Flexural fatigue and torsional resistance of ProFile GT and ProFile GT series X instruments. AB - INTRODUCTION: The purpose of this study was to compare the flexural fatigue and torsional resistance of ProFile GT and GT Series X instruments, taking into account their structural and dimensional characteristics. METHODS: Instrument diameter at each millimeter from the tip and pitch length were the dimensional parameters measured. Chemical composition was determined by energy-dispersive x ray spectroscopy and phase constitution by x-ray diffraction. Vickers microhardness measurements were performed to assess instrument strength. One group of 20/.06 GT and GTX instruments (n = 10 each) was tested until failure in a flexural fatigue test device, whereas another group of 20/.04 files (n = 10 each) was tested in torsion based on ISO 3630-1. RESULTS: GT and GTX instruments showed approximately the same chemical composition, namely 51at%Ni-49at%Ti (56wt%Ni-44wt%Ti) and contained mainly the beta-phase. GTX instruments showed higher intensity x-ray diffraction peaks and a statistically higher Vickers microhardness. There was a significant decrease in the diameter of GTX in relation to GT instruments from D6 to D9 for 20/.04 instruments and from D4 to D7 for 20/.06 instruments. Pitch length increased along the active part of both instruments, with a steeper increase in GTX. In general, GT Series X instruments were significantly more resistant to flexural fatigue than were similar GT instruments (p < 0.001) but exhibited lower torsional strength (p < 0.001). CONCLUSIONS: Different structural and dimensional characteristics were found in GTX instruments in comparison with GT instruments; this is probably the cause for their higher flexural fatigue resistance and lower torsional strength. PMID- 20307758 TI - Case report: Diagnosis and treatment of a botryoid odontogenic cyst found in the maxillary anterior region. AB - INTRODUCTION: The botryoid odontogenic cyst (BOC) is a multicompartmentalized variant of the lateral periodontal cyst (LPC) that is typically found in the premolar-canine region of the mandible. METHODS: A 60-year old man was referred for evaluation of a radiolucent lesion discovered on a routine examination. Radiographs revealed a unilocular radiolucency between the roots of teeth #10 and #11. Clinically, the site appeared normal with minimal probing depths, and there were no signs of swelling, bleeding, or mobility of the adjacent teeth. The pulps of both teeth responded to cold without lingering. After patient consent, the lesion was accessed by a mucoperiosteal flap, curetted from its bony cavity, and submitted for biopsy. The site was then treated with a bone allograft and a collagen membrane. RESULTS: The diagnosis of a BOC was made based on location and the histopathological findings of multiple cystic spaces lined by nonkeratinized stratified squamous epithelium. The 22-month follow-up revealed a normal clinical appearance with evidence of radiographic bone fill at the site of the lesion. CONCLUSION: This case shows an unusual presentation of a BOC in both location and radiographic appearance and emphasizes the importance of a microscopic examination of unilocular lesions when associated with teeth having normal responding vital pulps. The relatively high recurrence rate for the BOC warrants periodic follow-up. PMID- 20307757 TI - Effect of vapor lock on root canal debridement by using a side-vented needle for positive-pressure irrigant delivery. AB - INTRODUCTION: This study examined the effect of vapor lock on canal debridement efficacy by testing the null hypothesis that there is no difference between a "closed" and an "open" system design in smear layer and debris removal by using a side-vented needle for irrigant delivery. METHODS: Roots in the closed system were sealed with hot glue and embedded in polyvinylsiloxane to restrict fluid flow through the apical foramen during cleaning and shaping. For the open system, the apical foramen was enlarged and connected to the external environment via a channel within the polyvinylsiloxane to permit unrestricted fluid flow. Smear and debris scores were evaluated by using scanning electron microscopy and analyzed by using Cochran-Mantel-Haenszel statistic. RESULTS: No difference in smear scores was detected between the 2 systems at all canal levels. Significant differences in debris scores between the 2 systems were found at each canal level: coronal (P < .001), middle (P < .001), and apical (P < .001). CONCLUSIONS: The null hypothesis was rejected; presence of an apical vapor lock effect adversely affects debridement efficacy. Thus, studies with unspecified or questionable mechanisms to restrict fluid flow through the apical foramen have to be interpreted with caution. PMID- 20307759 TI - Orthodontic-surgical-endodontic management of unerupted maxillary central incisor with distoangular root dilaceration. AB - INTRODUCTION: Root dilaceration refers to a dental anomaly characterized by an abrupt deviation in the longitudinal axis of the tooth. It can be localized in the crown, between the crown and the root, or, most frequently, in the root. This report describes a horizontally unerupted maxillary central incisor with distoangular root dilacerations most likely caused by a traumatic dental injury to its primary predecessor. METHODS: Surgical-orthodontic traction was applied after the redistribution of the space in the anterior maxillary region. RESULTS: Root dilaceration of the tractioned tooth was evident and did not allow the alignment of the tooth into proper position in the dental arch. Root canal filling and apicoectomy were performed. This procedure restored the normal appearance of the anterior maxillary teeth. CONCLUSION: Long-term follow-up (8 years) by periapical radiography indicated stable periodontal health without the presence of root resorption. PMID- 20307761 TI - The view from the third rail. PMID- 20307760 TI - Effect of unintentionally extruded mineral trioxide aggregate in treatment of tooth with periradicular lesion: a case report. AB - INTRODUCTION: This case report describes the effect of unintentionally extruded mineral trioxide aggregate (MTA) into periradicular lesions and tissues on the prognosis of periradicular healing in maxillary left central incisor with periradicular lesion. METHODS: A 17-year-old girl with a large periradicular lesion from the apices of her maxillary left central to lateral incisors was referred. Tooth #9 had an open apex, but tooth #10 was normal. Conservative root canal treatment was performed to tooth #10. The apical third of the canal of tooth #9 was filled with MTA as an apical plug because of open apex. During this procedure, a radiograph was taken, and it showed an excessive extrusion of MTA into the periradicular lesion. The remaining canal space was filled with gutta percha and AH Plus sealer by using a lateral condensation technique. RESULTS: At follow-up examinations, the tooth was asymptomatic and radiographically showed repair of the lesion. Healing was achieved without any need for further endodontic surgical intervention. CONCLUSIONS: The results of this case showed that complete periapical healing is possible despite the extrusion of the MTA. This might be due to biologic properties of the MTA. Even so, extrusion of the filling material is not advocated. PMID- 20307762 TI - Investigation of impacted permanent teeth except the third molar in Chinese patients through an X-ray study. AB - PURPOSE: To investigate the incidence and the local factors of impacted permanent teeth, except for the third molar, in Chinese patients through an x-ray study. MATERIALS AND METHODS: A total of 548 impacted permanent teeth from panoramic radiographs were studied and recorded according to the patients' gender and age, tooth position, and classification of impaction. The local factors contributing to impacted permanent tooth were also investigated. RESULTS: The incidence of impacted permanent teeth in the Chinese was 6.15%. The impacted tooth showed a predilection for women and was more common in the maxilla. The impaction of the canine had the greatest occurrence, 28.10% of all impacted teeth. Vertical impaction was most common (49.09%). The chief local factor for impacted teeth was the lack of interdental space (49.64%). CONCLUSIONS: All permanent teeth can occur with impaction in Chinese patients. Dentists should perform a thorough evaluation before planning suitable treatment. PMID- 20307763 TI - Effect of nicotine on gene expression of angiogenic and osteogenic factors in a rabbit model of bone regeneration. AB - PURPOSE: This study aims to evaluate the influence of nicotine on the gene expression of osteogenic and angiogenic factors in bone regeneration by use of a nicotine-compromised rabbit model of mandibular lengthening. MATERIALS AND METHODS: Thirty adult New Zealand white rabbits were randomly assigned to the nicotine group or the control group. The total nicotine or placebo exposure time for all animals was 7 weeks. Unilateral mandibular distraction osteogenesis was performed. Five animals in each group were sacrificed at day 5, day 11, and day 18, respectively, after commencement of active distraction. The distraction regenerate samples were harvested, and the messenger ribonucleic acid expression of bone transforming growth factor beta(1), platelet-derived growth factor A, and basic fibroblast growth factor was assayed by real-time polymerase chain reaction analysis. RESULTS: The messenger ribonucleic acid expression of transforming growth factor beta(1), platelet-derived growth factor A, and basic fibroblast growth factor was significantly inhibited by nicotine exposure at a variety of time points. CONCLUSIONS: The presence of nicotine inhibited the gene expression of angiogenic and osteogenic factors resulting in compromised bone regeneration. PMID- 20307764 TI - Bisphosphonate-related osteonecrosis of the jaw associated with dental implants. AB - PURPOSE: Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is a well documented devastating side effect of long-term bisphosphonate (BP) use. There is scarce information in the literature on BRONJ associated with dental implants (DIs). The purpose of this study was to present a large series of cases of this association. PATIENTS AND METHODS: The files of all patients with BRONJ associated with DIs who were treated in the department of oral and maxillofacial surgery from 2003 to 2009 were reviewed. Data on demographics, medical background, type, and duration of BP treatment before the development of BRONJ, mode of therapy, and therapeutic outcome were retrieved. RESULTS: Of the 27 patients enrolled into the study, 11 (41%) developed BRONJ while taking oral BPs and 16 (59%) developed BRONJ associated with intravenous BPs. BRONJ developed after mean periods of 68 months (median, 60), 16.4 months (median, 13), and 50.2 months (median, 35) in patients on alendronate, zoledronic acid, and pamidronate, respectively. Only 6 patients developed BRONJ during the first 6 months after DI placement. When BP treatment had been started before DI placement, there was a mean duration of 16.2 months (median, 11) until the appearance of BRONJ development. Long-term antibiotics and only essential surgical procedures comprised the treatment of choice, and the response rate was considerably better for patients taking the oral type of BPs. There was no significant association between BRONJ and diabetes, steroid intake, or smoking habits. CONCLUSION: Patients undergoing BP treatment and who receive DIs require a prolonged follow up period to detect any development of BRONJ associated with DIs. PMID- 20307766 TI - "13-23-30" anatomic approach for maxillary full-arch implant reconstruction: a case report and surgical-prosthetic considerations. AB - For the past 30 years, implant treatment has been advocated for partially and fully edentulous patients to improve function, esthetics, phonetics, and comfort. Patients can now benefit from removable and fixed implant-retained and implant supported prostheses using the bone-anchoring techniques of endosseous osseointegrated implants. Much research has been done on complete maxillary implant reconstruction because of the large number of patients with edentulous maxillas and an enormous armamentarium of surgical-prosthetic implant techniques used in these cases. In the present article, one more technique is recommended, an anatomically based surgical-prosthetic approach--"13-23-30"--that should help a clinician with the initial selection of implant sites when contemplating an implant treatment of edentulous maxilla with a fixed 6-implant-supported hybrid prosthesis. This technique is based on the anatomy and function of mastication of natural dentition. The rationale behind this anatomic concept of treatment is discussed, and a case report is presented. PMID- 20307765 TI - Occurrence of bisphosphonate-related osteonecrosis of the jaw after surgical tooth extraction. AB - PURPOSE: To evaluate the occurrence of bisphosphonate-related osteonecrosis of the jaw (BRONJ) in patients exposed to nitrogen-containing bisphosphonates (NBPs) requiring surgical tooth extraction. PATIENTS AND METHODS: Sixty high-risk patients exposed to NBPs underwent surgical tooth extraction with bone biopsy and were treated with a 7-day cycle of oral antibiotics and discontinuation of NBPs for 1 month. BRONJ was defined as the occurrence of any BRONJ stage (0-3) at 3, 6, or 12 months of follow-up. Inferential analysis was performed on a per-bone (maxilla and/or mandible) basis (n = 72). The time to BRONJ was calculated, and age, gender, cancer diagnosis, and baseline osteomyelitis were evaluated as potential predictors. Exact logistic regression was used to model the time-to outcome relationship, and hazard rates were calculated from logistic probabilities. RESULTS: BRONJ was detected at 3 months' follow-up in 4 bones and at 6 months in 1 further bone. In the whole cohort of bones, the hazard rate of BRONJ was 5.6% at 3 months and 1.5% at 6 months. Baseline osteomyelitis was a strong risk factor for BRONJ development (odds ratio, 156.96; exact 95% confidence interval, 18.99 to infinity; exact P < .0001). CONCLUSION: In this 12 month follow-up study, BRONJ was a rare outcome in high-risk NBP users who underwent surgical tooth extraction. Moreover, baseline osteomyelitis was a very strong risk factor for BRONJ development. PMID- 20307767 TI - Effects of early functional loading on maintenance of free autogenous bone graft and implant osseointegration: an experimental study in dogs. AB - PURPOSE: The aim of the present study was to investigate the healing, integration, and maintenance of autogenous onlay bone grafts and implant osseointegration either loaded in the early or the delayed stages. MATERIALS AND METHODS: A total of 5 male dogs received bilateral blocks of onlay bone grafts harvested from the contralateral alveolar ridge of the mandible. On one side, the bone block was secured by 3 dental implants (3.5 mm x 13.0 mm, Osseospeed; AstraTech AB, Molndal, Sweden). Two implants at the extremities of the graft were loaded 2 days after installation by abutment connection and prosthesis (simultaneous implant placement group); the implant in the middle remained unloaded and served as the control. On the other side, the block was fixed with 2 fixation screws inserted in the extremities of the graft. Four weeks later, the fixation screws were replaced with 3 dental implants. The loading procedure (delayed implant placement group) was performed 2 days later, as described for the simultaneous implant placement sites. The animals were sacrificed 12 weeks after the grafting procedure. Implant stability was measured through resonance frequency analysis. The bone volume and density were assessed on computed tomography. The bone to implant contact and bone area in a region of interest were evaluated on histologic slides. RESULTS: The implant stability quotient showed statistical significance in favor of the delayed loaded grafts (P = .001). The bone-to-implant contact (P = .008) and bone area in a region of interest (P = 0.005) were significantly greater in the delayed group. Nevertheless, no difference was found in terms of graft volume and density between the early loaded and delayed-loaded approaches. CONCLUSIONS: The protocol in which the implant and bone graft were given delayed loading allows for effective quality of implant osseointegration and stabilization, with healing and remodeling occurring in areas near the implant resulting in denser bone architecture. PMID- 20307768 TI - Maxillary sinus floor augmentation and simultaneous implant placement using locally harvested autogenous bone chips and bone debris: a prospective clinical study. AB - PURPOSE: The aim of this study was to prospectively evaluate the status of implants, marginal bone loss, and outcome of maxillary sinus floor augmentation in patients undergoing maxillary sinus lift and simultaneous implant placement with the use of bone grafts harvested adjacent to the actual surgical site. MATERIALS AND METHODS: Patients in need of maxillary sinus floor augmentation to enable implant placement were enrolled in 2 different groups. In group A, a "bone trap" was used to harvest bone debris during implant preparation with additional bone collected by further drilling adjacent to the implant sites. In group B, a "bone scraper" was used to harvest cortical bone chips from the zygomatic buttress and from the lateral sinus wall before opening of a bony window. All patients were provided a fixed partial denture after a healing period of 3 to 6 months. A total of 61 patients with 81 Straumann implants (Institut Straumann AG, Basel, Switzerland) were assessed, with 17 patients (20 implants) in group A and 44 patients (61 implants) in group B. RESULTS: One implant was lost (in group B) before loading. The survival rate after a follow-up of 12 to 60 months was 98.8%. There was no significant difference in marginal bone loss on the mesial and distal sides of the implant when baseline to 1-year registration was compared with baseline to final registration. During the same time, graft height decreased significantly on the distal apical side of the implants. CONCLUSIONS: Bone grafts can be locally harvested at the site of the maxillary sinus augmentation procedure to enable placement, successful healing, and loading of 1 to 3 implants. PMID- 20307769 TI - Surgical management of a giant cavernous hemangioma involving the lower lip: report of a case and review of the literature. PMID- 20307770 TI - Bisphosphonate-related osteonecrosis of the jaw combined with jaw metastasis of prostate adenocarcinoma: report of a case. PMID- 20307771 TI - Low-grade fibromyxoid sarcoma: clinical study and case report. PMID- 20307772 TI - Is nevoid basal cell carcinoma syndrome really so rare? Proposal for an investigative protocol based on a case series. PMID- 20307773 TI - Interleukin 12 receptor beta1 chain deficiency in a child with disseminated tuberculosis: a case report. PMID- 20307774 TI - Endoscopically assisted repair of mandibular angle fractures. PMID- 20307775 TI - Simultaneous modified oblique Le Fort III and segmentalized Le Fort I osteotomies. PMID- 20307776 TI - Reconstructing large palate defects: the double buccinator myomucosal island flap. PMID- 20307777 TI - Buccinator myomucosal flap as soft tissue covering for vascularized free fibular flap in anterior maxillary bony defects. PMID- 20307778 TI - Sagittal split genioplasty: a new technique. PMID- 20307779 TI - The vacuum-assisted closure in treating craniofacial wounds. PMID- 20307780 TI - Modified palatal flap--a simpler approach for removal of palatal tori. PMID- 20307781 TI - Antibiotic prophylaxis in artificial joint patients. PMID- 20307782 TI - In reply to "Etiology of hyperparathyroidism in McCune-Albright syndrome". PMID- 20307783 TI - Removal of large complex odontoma using Le Fort I osteotomy. PMID- 20307785 TI - High cervical transmasseteric anteroparotid approach for low subcondylar fracture of mandible. PMID- 20307787 TI - Intracranial vascular lesions and anatomical variants all residents should know. AB - The purpose of this article is to extensively illustrate pathologically and clinically proven cases of intracranial vascular lesions and variants accumulated at a tertiary referral center. These are organized by normal anatomy and variants, arterial lesions, and venous lesions. High-quality computed tomography, computed tomographic angiography, magnetic resonance imaging, magnetic resonance angiography, 3D reconstruction, and angiographic figures illustrate the findings and complement a succinct review of this category of disease. Some cases are accompanied by histopathologic correlation. The reader of this article will gain or refresh information about intracranial vascular lesions and variants for clinical practice and for preparation for certifying examinations and clinical practice. The text and figures aid recognition of these entities and emphasize anatomy, clinical context, and differential diagnosis. These can aid the radiologist in arriving at the appropriate diagnosis. PMID- 20307788 TI - Vascular abnormalities of the spine: an imaging review. AB - The purpose of this educational article is to present a variety of vascular abnormalities of the spine to aid in recognition and accurate diagnosis. The lesions differ in clinical presentation, prognosis, and treatment. This has implications for patient care including treatment options. We provide an example based illustrated glossary to help the reader identify varying types of vascular spine lesions. Collected cross-sectional and angiographic imaging of the spine from our tertiary care institution provides a clear patient-based representation. PMID- 20307789 TI - How's your disk? Illustrative glossary of degenerative disk lesions using standardized lexicon. AB - The growing demand for structured reporting in radiology requires acceptance and familiarity of standard terms. This article clearly summarizes and illustrates the standard lexicon and classification scheme for degenerative lumbar disk pathology. First-year residents and veteran radiologists will gain/refresh knowledge of the lexicon for standard reporting. We provide an example-based illustrated glossary that contains diagrams and referenced descriptive explanations to illustrate disk lesions in the current standardized lexicon. Collected cross-sectional imaging of the spine from our tertiary care institution provides a clear patient-based representation of elements in the lexicon. PMID- 20307790 TI - Congratulations on the 10-year anniversary of the National Drug Abuse Treatment Clinical Trial Network--now, what's new for the coming decade? PMID- 20307791 TI - Equivalence of family functioning and externalizing behaviors in adolescent substance users of different race/ethnicity. AB - The Brief Strategic Family Therapy for Adolescent Drug Abuse clinical trial of 480 adolescents boys and girls aged 12 to 17 years and their parents was designed to maximize the chance that a sufficient number of Hispanic and Black adolescents would be included to allow valid subgroup comparisons. Examination of measurement invariance is an important step to ensure valid analysis. Two construct areas important to the analysis of trial results, adolescent problem behaviors, and family functioning showed a high degree of measurement invariance, which allowed valid comparisons of mean baseline differences across groups. Results showed that Black families had significantly higher initial levels of family functioning and lower levels of adolescent externalizing behaviors than either Hispanic or White non-Hispanic families. This pattern is consistent with an increased likelihood of referral of Black adolescents with more severe problems to restricted setting rather than to outpatient drug abuse treatment. This possibility highlights the importance of considering differing baseline characteristics of subgroups prior to assessing differential treatment effectiveness to prevent confounding. PMID- 20307792 TI - Study results from the Clinical Trials Network's first 10 years: where do they lead? AB - The National Drug Abuse Treatment Clinical Trials Network (CTN) began in 2000 with the goal of "improv[ing] the quality of drug abuse treatment throughout the country using science as the vehicle." Since then, 24 discrete clinical trials were launched, 20 are completed, and 15 have published main outcome papers. Of the latter, 4 tested pharmacological treatment, 8 psychosocial/behavioral treatment, 1 a combination of medication and counseling, and 2 targeted HIV/hepatitis C virus risk behavior. We review main study findings for these trials, including treatment retention, substance use or risk behavior outcomes, and secondary outcomes when analyzed. The purpose of this review is to identify the incremental progress toward improving drug treatment made by these trials and to propose next steps for the CTN and for the field arising from these studies. The CTN provides a unique opportunity to systematically design trials that incorporate treatment improvements from previous trials and to direct efforts toward innovations most likely to be incorporated into practice. PMID- 20307794 TI - The first decade of the National Drug Abuse Treatment Clinical Trials Network: bridging the gap between research and practice to improve drug abuse treatment. AB - The National Institute on Drug Abuse established the National Drug Abuse Treatment Clinical Trials Network (CTN) in 1999 to improve the quality of addiction treatment using science as the vehicle. The network brings providers from community-based drug abuse treatment programs and scientists from university based research centers together in an alliance that fosters bidirectional communication and collaboration. Collaboration enhanced the relevance of research to practice and facilitated the development and implementation of evidence-based treatments in community practice settings. The CTN's 20 completed trials tested pharmacological, behavioral, and integrated treatment interventions for adolescents and adults; more than 11,000 individuals participated in the trials. This article reviews the rationale for the CTN, describes the translation of its guiding principles into research endeavors, and anticipates the future evolution of clinical research within the Network. PMID- 20307793 TI - Partnerships and pathways of dissemination: the National Institute on Drug Abuse Substance Abuse and Mental Health Services Administration Blending Initiative in the Clinical Trials Network. AB - Since 2001, the National Drug Abuse Treatment Clinical Trials Network (CTN) has worked to put the results of its trials into the hands of community treatment programs, in large part through its participation in the National Institute on Drug Abuse-Substance Abuse and Mental Health Services Administration Blending Initiative and its close involvement with the Center for Substance Abuse Treatment's Addiction Technology Transfer Centers. This article describes (a) the CTN's integral role in the Blending Initiative, (b) key partnerships and dissemination pathways through which the results of CTN trials are developed into blending products and then transferred to community treatment programs, and (c) three blending initiatives involving buprenorphine, motivational incentives, and motivational interviewing. The Blending Initiative has resulted in high utilization of its products, preparation of more than 200 regional trainers, widespread training of service providers in most U.S. States, Puerto Rico, and the U.S. Virgin Islands and movement toward the development of Web-based implementation supports and technical assistance. Implications for future directions of the Blending Initiative and opportunities for research are discussed. PMID- 20307795 TI - A longitudinal study of organizational formation, innovation adoption, and dissemination activities within the National Drug Abuse Treatment Clinical Trials Network. AB - The National Institute on Drug Abuse established the National Drug Abuse Treatment Clinical Trials Network (CTN) to conduct trials of promising substance abuse treatment interventions in diverse clinical settings and to disseminate results of these trials. This article focuses on three dimensions of CTN's organizational functioning. First, a longitudinal dataset is used to examine CTN's formation as a network of interorganizational interaction among treatment practitioners and researchers. Data indicate strong relationships of interaction and trust, but a decline in problem-centered interorganizational interaction over time. Second, adoption of buprenorphine and motivational incentives among CTN's affiliated community treatment programs (CTPs) is examined over three waves of data. Although adoption is found to increase with CTPs' CTN participation, there is only modest evidence of widespread penetration and implementation. Third, CTPs' pursuit of the CTN's dissemination goals are examined, indicating that such organizational outreach activities are underway and likely to increase innovation diffusion in the future. PMID- 20307796 TI - From research to the real world: buprenorphine in the decade of the Clinical Trials Network. AB - The National Institute on Drug Abuse (NIDA) established the National Drug Abuse Treatment Clinical Trials Network (CTN) in 1999 to bring researchers and treatment providers together to develop a clinically relevant research agenda. Initial CTN efforts addressed the use of buprenorphine, a mu-opioid partial agonist, as treatment for opioid dependence. Strong evidence of buprenorphine's therapeutic efficacy was demonstrated in clinical trials involving several thousand opioid-dependent participants, and in 2002, the Food and Drug Administration approved buprenorphine for the treatment of opioid dependence. With the advent of a sublingual tablet containing both buprenorphine and naloxone to mitigate abuse and diversion (Suboxone), buprenorphine appeared poised to be the first-line treatment for opioid addiction. Notwithstanding its many attributes, certain implementation barriers remained to be addressed in CTN studies, and these efforts have brought a body of knowledge on buprenorphine to frontline clinicians. The purpose of this article is to review CTN-based buprenorphine research and related efforts to overcome challenges to the implementation of buprenorphine therapy in mainstream practice. Furthermore, this article explores current issues and future challenges that may require additional CTN efforts. PMID- 20307797 TI - Motivational incentives research in the National Drug Abuse Treatment Clinical Trials Network. AB - The purpose of this article is to review both main findings and secondary analyses from studies of abstinence incentives conducted in the National Drug Abuse Treatment Clinical Trials Network (CTN). Previous research has supported the efficacy of tangible incentives provided contingent on evidence of recent drug abstinence. CTN conducted the first multisite effectiveness trial of this novel intervention. Study participants were stimulant abusers (N = 803) participating in treatment at 14 clinical sites and randomly assigned to treatment as usual with or without a prize draw incentive program. Study participants could earn up to $400 over 3 months for submission of drug-free urine and breath (BAL) specimens. Three-month retention was significantly improved by incentives offered to psychosocial counseling clients (50% incentive vs. 35% control retained), whereas ongoing stimulant drug use was significantly reduced in methadone maintenance clients (54.4% incentive vs. 38.7% control samples testing stimulant-negative). In both settings, duration of continuous abstinence achieved was improved in the incentive condition. These studies support effectiveness of one abstinence incentive intervention and highlight the different outcomes that can be expected with application in methadone maintenance versus psychosocial counseling treatment settings. Secondary analyses have shown the importance of early treatment positive versus negative urine screens in moderating the outcome of abstinence incentives and have explored both safety and cost-effectiveness of the intervention. Implications for the use of motivational incentive methods in clinical practice are discussed. PMID- 20307798 TI - Using a latent variable approach to inform gender and racial/ethnic differences in cocaine dependence: a National Drug Abuse Treatment Clinical Trials Network study. AB - This study applies a latent variable approach to examine gender and racial/ethnic differences in cocaine dependence, to determine the presence of differential item functioning (DIF) or item-response bias to diagnostic questions of cocaine dependence, and to explore the effects of DIF on the predictor analysis of cocaine dependence. The analysis sample included 682 cocaine users enrolled in two national multisite studies of the National Drug Abuse Treatment Clinical Trials Network (CTN). Participants were recruited from 14 community-based substance abuse treatment programs associated with the CTN, including 6 methadone and 8 outpatient nonmethadone programs. Factor and multiple indicators-multiple causes (MIMIC) procedures evaluated the latent continuum of cocaine dependence and its correlates. MIMIC analysis showed that men exhibited lower odds of cocaine dependence than women (regression coefficient, beta = -0.34), controlling for the effects of DIF, years of cocaine use, addiction treatment history, comorbid drug dependence diagnoses, and treatment setting. There were no racial/ethnic differences in cocaine dependence; however, DIF by race/ethnicity was noted. Within the context of multiple community-based addiction treatment settings, women were more likely than men to exhibit cocaine dependence. Addiction treatment research needs to further evaluate gender-related differences in drug dependence in treatment entry and to investigate how these differences may affect study participation, retention, and treatment response to better serve this population. PMID- 20307799 TI - Pain and continued opioid use in individuals receiving buprenorphine-naloxone for opioid detoxification: secondary analyses from the Clinical Trials Network. AB - Pain complaints are common among individuals with opioid dependence. However, few studies investigate pain during opioid detoxification or the impact this pain has on continued opioid use. This secondary analysis utilized data from two Clinical Trials Network randomized controlled trials of buprenorphine-naloxone for short term opioid detoxification to examine the extent to which pain was associated with continued opioid use during and immediately following a 13-day detoxification protocol. At follow-up, more severe pain was associated with a greater number of self-reported days of opioid use during the prior 30 days (p < .05) but was not associated with urine toxicology results collected at follow-up. These results, although mixed, have potentially important clinical implications for assessing and addressing pain during opioid detoxification. Pain that is experienced during and immediately following medically monitored detoxification may be associated with continued opioid use. These findings lend further support for continued research on pain among patients with opioid dependence. PMID- 20307800 TI - Predicting outpatient treatment entry following detoxification for injection drug use: the impact of patient and program factors. AB - This article examines variables that predicted outpatient treatment entry within 6 months of residential detoxification. Patient data were collected from 632 injection drug users enrolled in a randomized trial conducted at eight detoxification programs within the National Drug Abuse Treatment Clinical Trials Network (CTN) with follow-up assessments conducted at 2, 8, 16, and 24 weeks. Detoxification program characteristics were collected during this study and from a survey of CTN treatment organizations. Survival analysis found that estimated proportions of reported outpatient treatment entry varied across sites from .06 to .72. A model-building approach determined variables significantly associated with outpatient treatment entry. The best predictive model contained five program level variables: accreditation, fewer beds, longer stays, shorter distance between detoxification and outpatient unit, and larger city population. Results suggest the importance of detoxification program characteristics in facilitating further treatment and the need for systems modifications to improve continuity of care. PMID- 20307801 TI - Multisite effectiveness trials of treatments for substance abuse and co-occurring problems: have we chosen the best designs? AB - Multisite effectiveness trials such as those carried out in the National Drug Abuse Treatment Clinical Trials Network (CTN) are a critical step in the development and dissemination of evidence-based treatments because they address how such treatments perform in real-world clinical settings. As Brigham et al. summarized in a recent article (G. S. Brigham, D. J. Feaster, P. G. Wakim, & C. L. Dempsey C. L., 2009), several possible experimental designs may be chosen for such effectiveness trials. These include (a) a new treatment intervention (Tx) is compared to an existing mode of community based treatment as usual (TAU): Tx versus TAU; (b) a new intervention is added to TAU and compared to TAU alone: Tx + TAU versus TAU; or (c) a new intervention is added to TAU and compared to a control condition added to TAU: Tx + TAU versus control + TAU. Each of these designs addresses a different question and has different potential strengths and weaknesses. As of December 2009, the primary outcome paper had been published for 16 of the multisite randomized clinical trials conducted in the CTN, testing various treatments for drug abuse, HIV risk behavior, or related problems. This paper systematically examines, for each of the completed trials, the experimental design type chosen and its original rationale, the main findings of the trial, and the strengths and weaknesses of the design in hindsight. Based on this review, recommendations are generated to inform the design of future effectiveness trials on treatments for substance abuse, HIV risk, and other behavioral health problems. PMID- 20307802 TI - Effect of smoking scenes in films on immediate smoking: a randomized controlled study. AB - BACKGROUND: The National Cancer Institute has concluded that exposure to smoking in movies causes adolescent smoking and there are similar results for young adults. PURPOSE: This study investigated whether exposure of young adult smokers to images of smoking in films stimulated smoking behavior. METHODS: 100 cigarette smokers aged 18-25 years were randomly assigned to watch a movie montage composed with or without smoking scenes and paraphernalia followed by a 10-minute recess. The outcome was whether or not participants smoked during the recess. Data were collected and analyzed in 2008 and 2009. RESULTS: Smokers who watched the smoking scenes were more likely to smoke during the break (OR=3.06, 95% CI=1.01, 9.29). In addition to this acute effect of exposure, smokers who had seen more smoking in movies before the day of the experiment were more likely to smoke during the break (OR=6.73, 95% CI=1.00, 45.25, comparing the top to bottom 5th percentiles of exposure). Level of nicotine dependence (OR=1.71, 95% CI=1.27, 2.32 per point on the Fagerstrom Test for Nicotine Dependence scale); contemplation (OR=9.07, 95% CI=1.71, 47.99) and precontemplation (OR=7.30, 95% CI=1.39, 38.36) stages of change; and impulsivity (OR=1.21, 95% CI=1.03, 1.43) were also associated with smoking during the break. Participants who watched the montage with smoking scenes and those with a higher level of nicotine dependence were also more likely to have smoked within 30 minutes after the study. CONCLUSIONS: There is a direct link between viewing smoking scenes and immediate subsequent smoking behavior. This finding suggests that individuals attempting to limit or quit smoking should be advised to refrain from or reduce their exposure to movies that contain smoking. PMID- 20307803 TI - Cigarette advertising and adolescent smoking. AB - BACKGROUND: Although most agree that the association between tobacco marketing and youth smoking is causal, few studies have assessed the specificity of this association. PURPOSE: This study aims to examine the specificity of the association between cigarette advertising and teen smoking. METHODS: A cross sectional survey of 3415 German schoolchildren aged 10-17 years was conducted using masked images of six cigarette brands and eight other commercial products in 2008. The exposure variable was a combination of contact frequency (recognition) and brand names (cued recall). Sample quartile (Q) exposure to advertisement exposure was calculated in 2009. Outcome variables were ever tried and current (monthly) smoking, and susceptibility to smoking among never smokers. RESULTS: The prevalence of ever smoking was 31.1% and that of current smoking was 7.4%, and 35.3% of never smokers were susceptible to smoking. Ad recognition rates ranged from 15% for a regionally advertised cigarette brand to 99% for a sweet. Lucky Strike and Marlboro were the most highly recognized cigarette brands (with ad recognition rates of 55% and 34%, respectively). After controlling for a range of established influences on smoking behaviors, the adjusted ORs for having tried smoking were 1.97 (95% CI=1.40, 2.77) for Q4 exposure to cigarette ads compared with adolescents in Q1, 2.90 (95% CI=1.48, 5.66) for current smoking, and 1.79 (95% CI=1.32, 2.43) for susceptibility to smoking among never smokers. Exposure to ads for commercial products other than cigarettes was significantly associated with smoking in crude but not multivariate models. CONCLUSIONS: This study underlines the specificity of the relationship between tobacco marketing and youth smoking, with exposure to cigarette ads, but not other ads, being associated with smoking behavior and intentions to smoke. This finding suggests a content-related effect of tobacco advertisements. PMID- 20307804 TI - Promoting primary care smoking-cessation support with quitlines: the QuitLink Randomized Controlled Trial. AB - BACKGROUND: Counseling by clinicians promotes smoking cessation, but in most U.S. primary care practices, it is difficult to provide more than brief advice to quit in the course of routine work. Telephone quitlines can deliver effective intensive counseling, but few collaborate closely with clinicians. PURPOSE: This study aimed to determine whether cessation support in practices is enhanced by a systems approach, in partnership with quitlines. DESIGN: A cluster RCT was used. SETTING/PARTICIPANTS: Participants included 1817 adult smokers from 16 primary care practices in the Virginia Ambulatory Care Outcomes Research Network. INTERVENTION: An expanded tobacco-use "vital sign" intervention (identify smokers, advise cessation, and assess readiness to quit) that was combined with fax referral of preparation-stage smokers to a quitline providing feedback to practices was compared to a traditional tobacco-use vital sign alone. MAIN OUTCOME MEASURES: The frequency of cessation support (in-office discussion of methods to quit or quitline referral) reported by patients in an exit survey (September 2005-July 2006, analyzed in 2008) was measured. RESULTS: The adjusted percentage of smokers who reported receiving cessation support differed by 12.5% in intervention and control practices (40.7% vs 28.2%, respectively; p<0.001). Both in-office discussion of methods to quit and quitline referral increased significantly with the intervention. Post hoc analysis revealed that the increase in cessation was stable for both patient gender and visit type and was more pronounced with patients aged 35-54 years and with male and more experienced clinicians. CONCLUSIONS: A systems approach to identifying smokers, advising and assessing readiness to quit, combined with a partnership with a quitline, increases delivery of cessation support for primary care patients beyond that accomplished by traditional tobacco-use vital sign screening alone. CLINICAL TRIAL REGISTRATION: NCT00112268. PMID- 20307805 TI - Television- and screen-based activity and mental well-being in adults. AB - BACKGROUND: Sedentary behavior is emerging as an independent risk factor for physical health, although there is no existing evidence regarding mental well being. PURPOSE: This study aimed to examine the association between recreational sedentary behavior (based on TV- and screen-based entertainment [TVSE] time) and mental health in a representative sample of adults. METHODS: Participants were 3920 men and women (mean age 51.0+/-15.8 years) from the 2003 Scottish Health Survey. The General Health Questionnaire (GHQ-12) and the mental health component of the 12-Item Short-Form Survey Instrument (MCS-12) were administered to obtain information on current mental health. Self-reported TVSE time, physical activity, and physical function was also measured. Analyses were conducted in 2009. RESULTS: Approximately 25% of participants engaged in at least 4 hours/day of TVSE. In general linear models, TVSE time per week was independently associated with GHQ-12 score (higher scores represent worse mental health status) after adjustment for age, gender, physical activity, physical function, area deprivation level, smoking, alcohol, fruit and vegetable intake, and BMI. After full adjustment, participants in the group with the highest TVSE level (>4 hours/day) had an increase in GHQ-12 score of 0.28 (95% CI=0.05, 0.51) compared with participants in the group with the lowest TVSE level (< or =2 hours/day). In stratified analyses, the association between TVSE time and GHQ-12 score persisted across all physical activity levels. Similar associations were observed using the MCS-12. CONCLUSIONS: Sedentary behavior in leisure time is independently associated with poorer mental health scores in a representative population sample. PMID- 20307806 TI - Racial disparities in hospitalizations for ambulatory care-sensitive conditions. AB - BACKGROUND: Variation in the quality of ambulatory care may be a key factor in explaining disparities in health, and these disparities have large cost implications. PURPOSE: This study identified differences in hospitalization rates for elderly African-American and white Marylanders for eight ambulatory care sensitive conditions (ACSCs). It assessed the relative contribution of race to disparities in preventable hospitalizations after controlling for demographic and socioeconomic factors as well as underlying prevalence. It also estimated the excess cost associated with these disparities. METHODS: Using prevention quality indicator specifications from the Agency for Healthcare and Research Quality applied to 2006 Medicare claims data, eight ACSC hospitalization measures were developed for 569,896 Maryland Medicare beneficiaries. The analysis was conducted in 2008. A Poisson regression model identified race, age, gender, and income as factors associated with differences in ACSC hospitalization rates. Excess costs were estimated from excess hospitalizations of African Americans and the median cost per admission. RESULTS: African Americans had significantly higher rates of ACSC hospitalizations than whites for five of eight conditions after controlling for demographic, socioeconomic, and geographic factors. Excess costs from disparities in quality ranged from $8 million (heart failure) to $38,000 (urinary tract infection). CONCLUSIONS: Race may be a key predictor of preventable hospitalizations for some ACSCs. Racial disparities in these hospitalizations represent excess costs to Medicare. Because ACSC admissions are potentially preventable with optimal ambulatory care, improving care for minority populations may reduce disparities and lower hospital costs. PMID- 20307807 TI - Cancer screening in Native Americans from the Northern Plains. AB - BACKGROUND: Native Americans from the Northern Plains have the highest age adjusted cancer mortality compared to Native Americans from any other region in the U.S. PURPOSE: This study examined the utilization and determinants of cancer screening in a large sample of Native Americans from the Northern Plains. METHODS: A survey was administered orally to 975 individuals in 2004-2006 from three reservations and among the urban Native-American community in the service region of the Rapid City Regional Hospital. Data analysis was conducted in 2007 2008. RESULTS: Forty-four percent of individuals reported ever receiving any cancer screening. Particularly low levels were found for breast, cervical, prostate, and colon cancer screening. In multivariate analyses, the strongest determinant of receiving cancer screening overall or cancer screening for a specific cancer site was recommendation for screening by a doctor or nurse. Other determinants associated with increased likelihood of ever having cancer screening included older age, female gender, and receiving physical exams more than once a year. Increased age was a determinant of breast cancer screening, and receiving physical exams was associated with cervical cancer screening. CONCLUSIONS: Cancer screening was markedly underutilized in this sample of Native Americans from the Northern Plains. Future research should evaluate the potential for improving cancer screening. PMID- 20307808 TI - Motivation for health screening: evaluation of social influence among Mexican American adults. AB - BACKGROUND: Americans of Mexican origin are at high risk for developing cardiovascular disease. PURPOSE: This study aimed to evaluate the associations between the presence of social network members who encourage screening and individuals' motivation to undergo three types of health screening: blood cholesterol, blood pressure, and blood glucose. The distinct roles of encouragers from different generations (older, same, and younger) were evaluated. METHODS: Adults of Mexican origin (N=452) aged 20-75 years from 162 households in Houston TX were included in this cross-sectional study by completing surveys in 2008 regarding their intentions to screen, health behaviors, illness beliefs, social networks, and family health history in either English or Spanish. Data were analyzed in 2009. RESULTS: About one third of the participants reported having at least one same-generation network member who encouraged screening; smaller proportions reported having at least one older- (17% to 19%) and one younger generation (11% to 12%) encourager. The presence of at least one older-generation encourager was associated with higher levels of intention to screen for all three screenings controlling for sociodemographic characteristics and illness beliefs. Having at least one same-generation encourager was associated with higher levels of intention to screen for blood cholesterol. CONCLUSIONS: Social influence may play an important role in motivating individuals to engage in screenings. Network based intervention involving older individuals to provide encouragement to younger network members should be explored as a means to increase motivation to screen among this population. PMID- 20307809 TI - Diabetes risk reduction behaviors among U.S. adults with prediabetes. AB - BACKGROUND: Diabetes can be prevented or delayed in high-risk adults through lifestyle modifications, including dietary changes, moderate-intensity exercise, and modest weight loss. However, the extent to which U.S. adults with prediabetes are making lifestyle changes consistent with reducing risk is unknown. PURPOSE: This study aimed to study lifestyle changes consistent with reducing diabetes risk and factors associated with their adoption among adults with prediabetes. METHODS: In 2009, data were analyzed from 1402 adults aged > or =20 years without diabetes who participated in the 2005-2006 National Health and Nutrition Examination Survey and had valid fasting plasma glucose and oral glucose tolerance tests. The extent to which adults with prediabetes report that in the past year they tried to control or lose weight, reduced the amount of fat or calories in their diet, or increased physical activity or exercise was estimated and factors associated with the adoption of these behaviors were examined. RESULTS: Almost 30% of the U.S. adult population had prediabetes in 2005-2006, but only 7.3% (95% CI=5.5%, 9.2%) were aware they had it. About half of adults with prediabetes reported performing diabetes risk reduction behaviors in the past year, but only about one third of adults with prediabetes had received healthcare provider advice about these behaviors in the past year. In multivariate analyses, provider advice, female gender, and being overweight or obese were positively associated with all three risk reduction behaviors. CONCLUSIONS: Adoption of risk reduction behaviors among U.S. adults with prediabetes is suboptimal. Efforts to improve awareness of prediabetes, increase promotion of healthy behaviors, and improve availability of evidence-based lifestyle programs are needed to slow the growth in new cases of diabetes. PMID- 20307810 TI - Physical activity and mortality risk in the Japanese elderly: a cohort study. AB - BACKGROUND: Physical activity recommendations for older adults with poor health needs to be understood. PURPOSE: This study aims to examine the association between the frequency of physical activity and mortality among a sample of elderly subjects, most of whom were under treatment for pre-existing disease. METHODS: Data on the frequency of leisure-time physical activity, walking for transportation, and non-exercise physical activity were obtained from a population-based cohort study in Shizuoka, Japan. Of the randomly selected 22,200 residents aged 65-84 years, 10,385 subjects were followed from 1999 to 2006 and analyzed. Hazard ratios (HRs) and 95% CIs were obtained for all-cause; cardiovascular disease (CVD); and cancer mortality, after adjusting for covariates such as pre-existing disease(s). A subgroup analysis that was restricted to subjects under treatment for pre-existing disease(s) at baseline was further conducted. Data were collected between 1999 and 2006, and all analyses were conducted in 2008 and 2009. RESULTS: Every physical activity was associated with a reduced risk of all-cause and CVD mortality, among not only the total sample but even those under treatment. The HRs for CVD mortality among participants with 5 or more days of non-exercise physical activity per week for the total sample and those with pre-existing disease(s) were 0.38 (95% CI=0.22, 0.55) and 0.35 (95% CI=0.24, 0.52), respectively, compared with no non-exercise physical activity. The association between physical activity and cancer mortality was not clear. CONCLUSIONS: This study suggests a protective effect of physical activity on all-cause and CVD mortality among Japanese elderly people with pre existing disease. PMID- 20307811 TI - Lower-body function, neighborhoods, and walking in an older population. AB - BACKGROUND: Poor lower-body capacity is associated with reduced mobility in older populations. PURPOSE: This study sought to determine whether neighborhood environments (e.g., land-use patterns and safety) moderate that association. METHODS: The study is based on a cross-sectional sample of 884 people aged > or =65 years identified through service organizations in Alameda County CA, Cook County IL, Allegheny County PA, and Wake and Durham counties NC. In-person interviews focused on neighborhood characteristics, physical and cognitive function, and physical activity and walking. Functional capacity was tested using measures of lower-body strength, balance, and walking speed. The main outcome was time spent walking in a typical week (<150 vs > or =150 minutes per week). Objective environmental measures were also included. Estimates of main and interaction effects were derived from regression models. RESULTS: Living in a residential area, compared to a mixed-use or commercial area, was associated with less time spent walking (<150 minutes per week; OR=1.57, 95% CI=1.04, 2.38). Living in a less-compact area (greater median block length) is also significantly associated with less walking for seniors, but only among those with excellent lower-body strength. CONCLUSIONS: Neighborhood type is associated with walking among older people, as it is among the general adult population. In individuals with poor lower-body function, no association was found between residence in a less-compact area and walking. For those people, the relationship between neighborhood characteristics and walking requires further study. PMID- 20307812 TI - The built environment and location-based physical activity. AB - BACKGROUND: Studies of the built environment and physical activity have implicitly assumed that a substantial amount of activity occurs near home, but in fact the location is unknown. PURPOSE: This study aims to examine associations between built environment variables within home and work buffers and moderate-to vigorous physical activity (MVPA) occurring within these locations. METHODS: Adults (n=148) from Massachusetts wore an accelerometer and GPS unit for up to 4 days. Levels of MVPA were quantified within 50-m and 1-km home and work buffers. Multiple regression models were used to examine associations between five objective built environment variables within 1-km home and work buffers (intersection density, land use mix, population and housing unit density, vegetation index) and MVPA within those areas. RESULTS: The mean daily minutes of MVPA accumulated in all locations=61.1+/-32.8, whereas duration within the 1-km home buffers=14.0+/-16.4 minutes. Intersection density, land use mix, and population and housing unit density within 1-km home buffers were positively associated with MVPA in the buffer, whereas a vegetation index showed an inverse relationship (all p<0.05). None of these variables showed associations with total MVPA. Within 1 km of work, only population and housing unit density were significantly associated with MVPA within the buffer. CONCLUSIONS: Findings are consistent with studies showing that certain attributes of the built environment around homes are positively related to physical activity, but in this case only when the outcome was location-based. Simultaneous accelerometer-GPS monitoring shows promise as a method to improve understanding of how the built environment influences physical activity behaviors by allowing activity to be quantified in a range of physical contexts and thereby provide a more explicit link between physical activity outcomes and built environment exposures. PMID- 20307814 TI - Dissemination and implementation research on community-based cancer prevention: a systematic review. AB - CONTEXT: An extensive array of effective interventions for the prevention of cancer exists, suggesting that evidence is ready for widespread use. However, few of these approaches have been extensively utilized in real-world settings. Further, little is known on how to best disseminate and implement evidence-based interventions for the primary prevention of cancer in community settings. EVIDENCE ACQUISITION: A systematic review of the dissemination and implementation literature was conducted between 2006 and 2008 in the topic areas of smoking, healthy diet, physical activity, and sun protection. English-language peer reviewed articles published between 1980 and 2008 that met the inclusion criteria were classified by suitability of study design (i.e., greatest, moderate, least); quality of execution (i.e., good, fair, limited); and effectiveness (i.e., substantial, some, or little/no evidence of effectiveness) and were abstracted for dissemination- and implementation-related content. EVIDENCE SYNTHESIS: Twenty five unique dissemination and implementation studies were identified. The majority of included studies were conducted in the U.S., in schools, and with children as the ultimate target population, had the least suitability of study design, had fair or limited execution, and used a theoretic framework, active dissemination and implementation approaches, and multimodal strategies. There was considerable heterogeneity across studies in reported mediators, moderators, and outcomes. CONCLUSIONS: Key implications from this review include the need for uniform language, studies targeting various populations and settings, valid and reliable measures, triangulation of and more practice-based evidence, standardized reporting criteria, and active and multimodal strategies. PMID- 20307813 TI - Knowledge gaps and misconceptions about coronary heart disease among U.S. South Asians. AB - BACKGROUND: Although South Asians are at higher risk for coronary heart disease (CHD) than most other U.S. racial/ethnic groups, very little research has addressed this disparity. PURPOSE: As a first step in developing culturally targeted CHD prevention messages for this rapidly growing community, this study examined South Asians' knowledge and beliefs about CHD. METHODS: Analyses, conducted in 2009, were based on data collected from January to July 2008 in a cross-sectional study population of 270 South Asian adults in Illinois. Interviews were conducted in English, Hindi, or Urdu using a standardized questionnaire. Multivariate regression models were used to examine the associations between sociodemographics and CHD knowledge and attitudes about preventability. RESULTS: Eighty-one percent of respondents had one or more CHD risk factors. Most participants (89%) said they knew little or nothing about CHD. Stress was the most frequently mentioned risk factor (44%). Few mentioned controlling blood pressure (11%); cholesterol (10%); and diabetes (5%) for prevention. Fifty-three percent said that heart attacks are not preventable. Low education level, being interviewed in Urdu or Hindi, and low level of acculturation were associated with less knowledge and believing that CHD is not preventable. CONCLUSIONS: A majority of South Asians in this study believed that CHD is not preventable and had low awareness of modifiable risk factors. As a first step, CHD education should target the knowledge gaps that may affect risk factor control and behavior change. Educational messages may need to be somewhat different for subgroups (e.g., by education and language) to be maximally effective. PMID- 20307815 TI - The worldwide battle against soft drinks in schools. AB - Sugar-sweetened beverages are widely believed to be contributing to the growing prevalence of overweight and obesity around the world. One of the channels used by industry to encourage greater consumption and preferences for soft drinks is schools. But governments around the world are taking action to limit the availability of soft drinks in schools. More than 30 national and subnational governmental bodies have made efforts to restrict availability, and the soft drinks industry has also taken some limited voluntary action. Most government-led efforts-with some exceptions-restrict the availability of any drink with added sugar, but the voluntary pledges take less-restrictive approaches. There is little consensus on artificially sweetened drinks. Policies vary in other ways, too, presenting an opportunity to study the effects of different policy approaches on short- and long-term consumption and attitudes. In the meantime, the widespread condemnation of soft drinks in schools suggests that it is within the industry's interests to take more comprehensive action. PMID- 20307816 TI - Continuing issues for dissemination and implementation of cancer prevention interventions. PMID- 20307817 TI - Lost opportunities in accessing reproductive health care--can pediatricians still make a difference? PMID- 20307818 TI - Which adolescents have opportunities to talk to doctors alone? PMID- 20307819 TI - A meta-analysis of obesity interventions among U.S. minority children. AB - PURPOSE: To quantitatively evaluate the efficacy of interventions designed to prevent or treat obesity among U.S. minority children using meta-analytic techniques. METHODS: A total of 40 intervention trials involving 10,725 children aged 6-19 years were examined. RESULTS: Interventions with more components showed a higher mean effect size than those with fewer components: among 32 controlled trials, d = .07 for one-component (n = 6); d = .08 for two-component (n = 15); d = .33 for three-component (n = 10); and d = .71 for four-component (n = 1) interventions. Interventions with parental involvement (n = 22, d = .21) and lifestyle interventions (n = 14, d = .34) showed a greater mean effect size than those without parental involvement (n = 10, d = .05) or lifestyle interventions (n = 18, d = .04), despite the fact that their 90% confidence intervals overlapped. Among uncontrolled trials (n = 8), two-component interventions (n = 5) yielded d = .86 and three-component interventions (n = 3) yielded d = .96. CONCLUSIONS: Evidence indicates that, among U.S. minority children, obesity interventions with three or more components might be more efficacious than those using fewer components. Parental involvement, lifestyle change, culturally-based adaptation, and interactive computer programs seem to show promise in the reduction of obese minority children. PMID- 20307820 TI - Utilization of health services in physician offices and outpatient clinics by adolescents and young women in the United States: implications for improving access to reproductive health services. AB - PURPOSE: We examined utilization patterns of adolescents and young women as they seek general and reproductive health services in physician offices and hospital outpatient clinics. METHODS: We analyzed physician office visits in the 2003-2006 National Ambulatory Medical Care Surveys, and hospital outpatient clinic visits in the National Hospital Ambulatory Medical Care Surveys, to examine utilization patterns of females aged 9-26 years by 2-year age intervals and other characteristics such as physician specialty or clinic type. RESULTS: The number of visits to primary care physician offices increased with age, from 4.9 million for ages 9-10 years to 9.0 million for ages 25-26 years. The proportion of visits made to obstetrician-gynecologists and family practitioners increased with age, and by ages 15-16 years fewer than half of all visits to primary care providers were made to pediatricians. The proportion of visits to family practitioners increased from 25% at ages 9-10 years to 30% at ages 25-26 years. By ages 17-18 years, a larger proportion of visits were made to obstetrician-gynecologists (33% of 7.0 million visits) and to family practitioners (34%) than to pediatricians (23%). The proportion of visits for reproductive health services peaked at 53% of 7.5 million physician visits at ages 20-21 years. Similar utilization patterns were observed for the 11.0 million hospital outpatient visits to primary care providers. CONCLUSIONS: Because adolescents and young women most commonly utilize healthcare services provided by obstetrician-gynecologists and family practitioners, these specialties should be priority targets for interventions to improve the quality and availability of reproductive health services. PMID- 20307821 TI - Parenting style as a predictor of adolescent weight and weight-related behaviors. AB - PURPOSE: Current research indicates that specific parenting styles are associated with adolescent overweight, dietary intake, and physical activity; but most of the research has been cross-sectional, making it difficult to determine the temporal order of these associations. The current study adds to the previous research by examining 5-year longitudinal associations between parenting style and adolescent weight and weight-related behaviors. METHODS: Data from Project EAT, a population-based study with adolescents from diverse ethnic and socioeconomic backgrounds, were used. Adolescents (N = 2,516) from 31 Minnesota schools completed in-class assessments in 1999 (Time 1) and mailed surveys in 2004 (Time 2). Multiple linear regression models were used to predict mean levels of adolescent outcomes at Time 2 from parenting style at Time 1. RESULTS: Time 1 maternal authoritative parenting style predicted lower body mass index in adolescent sons and daughters at Time 2. Time 1 paternal permissive parenting style predicted more fruits and vegetables intake in daughters at Time 2. Significant associations were not found between parenting style and adolescent physical activity. CONCLUSIONS: Findings suggest that authoritative parenting style may play a protective role related to adolescent overweight and that the dimension of warmth and/or caring in the parent-adolescent relationship may be important in relation to female adolescent healthy dietary intake. Further exploration of opposite sex parent-adolescent dyad patterns related to parenting style and adolescent weight and weight-related behaviors is warranted. PMID- 20307822 TI - Television use and snacking behaviors among children and adolescents in China. AB - PURPOSE: Television (TV) use has been linked with poor eating behaviors and obesity in young people. This study examines the association between TV watching and paying attention to TV commercials with buying and requesting snacks seen on commercials, and eating snacks while watching TV among youth in China. METHODS: Data from 1,552 participants (ages 6-17.99) in the 2004 China Health and Nutrition Survey were analyzed cross-sectionally. The 2004 China Health and Nutrition Survey was conducted in nine Chinese provinces. RESULTS: Most respondents (92.2%) reported watching TV; on average children (6-11.99 years old) and adolescents (12-17.99 years old) watched TV for 9-10 hours per week. Nearly half (42.9%) of all the respondents said they "sometimes" or "often" paid attention to TV commercials. Respondents who reported paying attention to commercials had higher odds of requesting snacks (odds ratio [OR] = 3.43; 95% confidence interval [CI] = 2.55-4.60) and buying snacks (OR = 2.73; 95% CI = 2.17 3.43) seen on TV, and eating snacks while watching TV (OR = 1.60; 95% CI = 1.23 2.07) than those who did not pay attention. However, frequency of watching TV was not significantly related to snacking. CONCLUSION: Attention to TV commercials for snack foods may be one of the factors affecting the increase in obesity among children and adolescents in China. PMID- 20307823 TI - Randomized controlled clinical trial of yoga in the treatment of eating disorders. AB - PURPOSE: This was a pilot project designed to assess the effect of individualized yoga treatment on eating disorder outcomes among adolescents receiving outpatient care for diagnosed eating disorders (anorexia nervosa, bulimia nervosa, eating disorder not otherwise specified). METHODS: A total of 50 girls and 4 boys aged 11-21 years were randomized to an 8-week trial of standard care vs. individualized yoga plus standard care. Of these, 27 were randomized to standard care and 26 to yoga plus standard care (attrition: n = 4). Standard care (every other week physician and/or dietician appointments) was required to meet ethical guidelines. The No Yoga group was offered yoga after study completion as an incentive to maintain participation. Outcomes evaluated at baseline, end of trial, and 1-month follow-up included Eating Disorder Examination (EDE), Body Mass Index (BMI), Beck Depression Inventory, State-Trait Anxiety Inventory, and Food Preoccupation questionnaire. RESULTS: The Yoga group demonstrated greater decreases in eating disorder symptoms. Specifically, the EDE scores decreased over time in the Yoga group, whereas the No Yoga group showed some initial decline but then returned to baseline EDE levels at week 12. Food preoccupation was measured before and after each yoga session, and decreased significantly after all sessions. Both groups maintained current BMI levels and decreased in anxiety and depression over time. CONCLUSIONS: Individualized yoga treatment decreased EDE scores at 12 weeks, and significantly reduced food preoccupation immediately after yoga sessions. Yoga treatment did not have a negative effect on BMI. Results suggest that individualized yoga therapy holds promise as adjunctive therapy to standard care. PMID- 20307824 TI - Does resistance training improve the functional capacity and well being of very young anorexic patients? A randomized controlled trial. AB - PURPOSE: We determined the effects of a 3-month low-moderate-intensity strength training program (2 sessions/week) on functional capacity, muscular strength, body composition, and quality of life (QOL) in 22 young (12-16 yrs) anorexic outpatients. METHODS: Patients were randomly assigned to a training or control group (n=11 [10 females] each). Training sessions were of low intensity (loads for large muscle groups ranging between 20%-30% and 50%-60% of six repetitions maximum [6RM] at the end of the program). We measured functional capacity by the time up and go and the timed up and down stairs tests. Muscular strength was assessed by 6RM measures for seated bench and leg presses. We estimated percent body fat and muscle mass. We assessed patients' QOL with the Short Form-36 items. RESULTS: The intervention was well tolerated and did not have any deleterious effect on patients' health, and did not induce significant losses in their body mass. The only studied variable for which a significant interaction (group x time) effect was found (p=.009) was the 6RM seated lateral row test. CONCLUSIONS: Low-moderate-intensity strength training does not seem to add major benefits to conventional psychotherapy and refeeding treatments in young anorexic patients. PMID- 20307825 TI - The causal impact of childhood-limited maltreatment and adolescent maltreatment on early adult adjustment. AB - PURPOSE: We use full-matching propensity score models to test whether developmentally specific measures of maltreatment, in particular childhood limited maltreatment versus adolescent maltreatment, are causally related to involvement in crime, substance use, health-risking sex behaviors, and internalizing problems during early adulthood. METHODS: Our design includes 907 participants (72% male) in the Rochester Youth Development Study, a community sample followed from age 14 to age 31 with 14 assessments, including complete maltreatment histories from Child Protective Services records. RESULTS: After balancing the data sets, childhood-limited maltreatment is significantly related to drug use, problem drug use, depressive symptoms, and suicidal thoughts. Maltreatment during adolescence has a significant effect on a broader range of outcomes: official arrest or incarceration, self-reported criminal offending, violent crime, alcohol use, problem alcohol use, drug use, problem drug use, risky sex behaviors, self-reported sexually transmitted disease diagnosis, and suicidal thoughts. CONCLUSIONS: The causal effect of childhood-limited maltreatment is focused on internalizing problems, whereas adolescent maltreatment has a stronger and more pervasive effect on later adjustment. Increased vigilance by mandated reporters, especially for adolescent victims of maltreatment, along with provision of appropriate services, may prevent a wide range of subsequent adjustment problems. PMID- 20307826 TI - Sexual orientation and bullying among adolescents in the growing up today study. AB - PURPOSE: To examine the relationship between sexual orientation and past-year reports of bullying victimization and perpetration in a large sample of American youth. METHODS: Survey data from 7,559 adolescents aged 14-22 who responded to the 2001 wave questionnaire of the Growing Up Today Study were examined cross sectionally. Multivariable generalized estimating equations regression was performed using the modified Poisson method. We examined associations between sexual orientation and past-year bully victimization and perpetration with heterosexuals as the referent group, stratifying by gender and controlling for age, race/ethnicity, and weight status. RESULTS: Compared to heterosexual males, mostly heterosexual males (risk ratio [RR]: 1.45; 95% confidence interval [CI]: 1.13, 1.86) and gay males (RR 1.98; CI: 1.39, 2.82) were more likely to report being bullied. Similarly, mostly heterosexual females (RR: 1.72, 95% CI: 1.45, 2.03), bisexual females (RR: 1.63, 95% CI: 1.14, 2.31), and lesbians (RR: 3.36, 95% CI: 1.76, 6.41) were more likely to report being bullied than were heterosexual females. Gay males (RR: 0.34, 95% CI: 0.14, 0.84) were much less likely to report bullying others than were heterosexual males. Mostly heterosexual females (RR: 1.70, 95% CI: 1.42, 2.04) and bisexual females (RR: 2.41, 95% CI: 1.80, 3.24) were more likely to report bullying others than heterosexual females. No lesbian participants reported bullying others. CONCLUSIONS: There are significant differences in reports of bullying victimization and perpetration between heterosexual and sexual minority youth. Clinicians should inquire about sexual orientation and bullying, and coordinate care for youth who may need additional support. PMID- 20307827 TI - Gender and the effects of an economic empowerment program on attitudes toward sexual risk-taking among AIDS-orphaned adolescent youth in Uganda. AB - PURPOSE: This article examines gender differences in attitudes toward sexual risk taking behaviors of acquired immune deficiency syndrome (AIDS)-orphaned youth participating in a randomized control trial testing an economic empowerment intervention in rural Uganda. METHODS: Adolescents (average age 13.7 years) who had lost one or both parents to AIDS from 15 comparable schools were randomly assigned to either an experimental (n=135) or a control condition (n=142). Adolescents in the experimental condition, in addition to usual care, also received support and incentives to save money toward secondary education. RESULTS: Findings indicate that although adolescent boys and girls within the experimental condition saved comparable amounts, the intervention appears to have benefited girls, in regard to the attitudes toward sexual risk-taking behavior, in a different way and to a lesser extent than boys. CONCLUSIONS: Future research should investigate the possibility that adolescent girls might be able to develop equally large improvements in protective attitudes toward sexual risk taking through additional components that address gendered social norms. PMID- 20307828 TI - Factors associated with intention-to-recommend human papillomavirus vaccination among physicians in Mysore, India. AB - PURPOSE: This qualitative study investigated physician intention-to-recommend the human papillomavirus (HPV) vaccine to parents of adolescent girls in India. There are currently no data on attitudes to HPV vaccination among healthcare providers in India. METHODS: Between June and August 2008, 20 semistructured qualitative in depth interviews were conducted among physicians from a range of specialties and practice settings in Mysore District, India. Physicians were interviewed about their specialty and the types of patients they saw in their practice, attitudes toward recommending HPV vaccination to parents of adolescent girls, perceived subjective norms surrounding the promotion of vaccines in their work settings, and their perceptions regarding self-efficacy in recommending the HPV vaccine. RESULTS: The study found that knowledge about HPV infection and its relationship to cervical cancer was low among physicians across specialties. While most physicians expressed positive attitudes toward vaccination in general, and HPV vaccination in particular, the overwhelming majority believed that few of their patients would react positively to a vaccine recommendation. Physicians were concerned about talking to parents about their adolescent daughters' reproductive lives. Certain specialties, particularly obstetrician/gynecologists, suggested that recommending immunization was not appropriate in their work setting. CONCLUSION: With the HPV vaccine recently being approved in India, there is a strong need to provide more education for physicians about the relationship of HPV infection and cervical cancer and the benefits of vaccinating adolescent girls to prevent cervical cancer in the future. PMID- 20307829 TI - Adolescents' perceptions of cigarette brand image: does plain packaging make a difference? AB - PURPOSE: To examine the effect of plain packaging on adolescents' perceptions of cigarette packs, attributes of smokers, and expectations of cigarette taste, and to identify the effect of increasing the size of pictorial health warnings on appraisal of plain packs. METHODS: We used a 5 (degree of plain packaging and graphic health warning)x 3 (brand type) between-subjects experimental design, using a Web-based methodology to expose adolescents to one randomly selected cigarette pack, during which respondents completed ratings. RESULTS: When brand elements such as color, branded fonts, and imagery were progressively removed from cigarette packs, adolescents perceived packs to be less appealing, rated attributes of a typical smoker of the pack less positively, and had more negative expectations of cigarette taste. Pack appeal was reduced even further when the size of the pictorial health warning on the most plain pack was increased from 30% to 80% of the pack face, with this effect apparent among susceptible nonsmokers, experimenters, and established smokers. CONCLUSIONS: Removing as much brand information from cigarette packs as possible is likely to reduce positive cigarette brand image associations among adolescents. By additionally increasing the size of pictorial health warnings, positive pack perceptions of those who are at greater risk of becoming regular addicted adult smokers are most likely to be reduced. PMID- 20307830 TI - Who gets confidential care? Disparities in a national sample of adolescents. AB - Using the 2001-2004 Medical Expenditures Panel Survey, we examined rates of past year adolescent time alone with a clinician by visit type, and among youths with a preventive visit, examined age, gender, and race/ethnicity differences. Youths with a preventive visit have higher rates of time alone; rates for these youths increase with age, are higher for males (42%) versus females (37%), and are lowest among Hispanics. Time alone rates are low, especially for younger females and Hispanic youths. Special efforts are needed to increase time alone in these populations. PMID- 20307831 TI - Thriving in stepfamilies: exploring competence and well-being among African American youth. AB - Although scholars conclude that children/adolescents in two-parent nuclear families have an advantage over those in stepfamilies, emerging evidence indicates that the experiences of African American youths have been overshadowed. In three replicated studies, we detected no differences on several important and commonly assessed well-being and competence indicators among samples of African American youth in two-parent nuclear and stepfamilies. PMID- 20307832 TI - Prevalence of insufficient, borderline, and optimal hours of sleep among high school students - United States, 2007. AB - We describe the prevalence of insufficient, borderline, and optimal sleep hours among U.S. high school students on an average school night. Most students (68.9%) reported insufficient sleep, whereas few (7.6%) reported optimal sleep. The prevalence of insufficient sleep was highest among female and black students, and students in grades 11 and 12. PMID- 20307833 TI - Recreational versus nonrecreational prescription borrowing: time for an expanded conceptualization? PMID- 20307834 TI - Measurement problems in assessing adolescent exposure to alcohol advertising in magazines. PMID- 20307838 TI - Adolescent males and human papillomavirus: psychosexual development, infection, and vaccination. PMID- 20307839 TI - Human papillomavirus-related disease in men: not just a women's issue. AB - The most common cause of mortality related to human papillomavirus (HPV) infection is cervical cancer. However, male HPV infection is also an important concern, both for the disease burden in men and for the risk of transmission to women. HPV is associated with a variety of cancers in men, including anal cancer and a subset of penile and oral cancers. The incidence of anal and oral cancers related to HPV is increasing in the general population and is growing even faster among individuals who are immunocompromised because of human immunodeficiency virus (HIV) infection. Penile HPV infection is very common among heterosexual men and remains high throughout a wide range of ages. Likewise, anal HPV infection and anal intraepithelial neoplasia are very common throughout a wide range of ages in both HIV-negative and HIV-positive men who have sex with men. Other HPV related diseases of clinical importance in men include condylomata acuminata (genital warts) and recurrent respiratory papillomatosis. The quadrivalent HPV vaccine has been shown to be highly efficacious in the prevention of genital warts in women and precancerous lesions of the cervix, vulva, and vagina. In addition, recent interim data have shown that the quadrivalent HPV vaccine is highly effective in reducing external genital lesions in young men. Although the protective efficacy of HPV vaccination in men has not yet been fully established pending the outcome of public policy discussions and cost-efficacy studies-there may be a strong rationale for vaccinating boys, similar to girls, at an early age when they have had limited or no prior sexual activity. PMID- 20307840 TI - Beyond cervical cancer: burden of other HPV-related cancers among men and women. AB - Human papillomavirus (HPV) infection is a necessary cause of cervical cancer, and is etiologically associated with a subset of cancers of the anus, oropharynx, penis, vagina, and vulva. Current data indicate that HPV infection is potentially associated with 90%-93% of anal cancers, 12%-63% of oropharyngeal cancers, 36% 40% of penile cancers, 40%-64% of vaginal cancers, and 40%-51% of vulvar cancers. HPV infection accounts for up to 492,800 cervical cancers and 97,215 cases of noncervical HPV-related cancers worldwide during 2002, including up to 50,780 cancers among men (13,485 anal cancers, 26,775 oropharyngeal cancers, and 10,520 penile cancers) and up to 46,435 cancers among women (14,787 anal cancers, 6,048 oropharyngeal cancers, and 25,600 vaginal/vulvar cancers). In the United States annually (1998-2003), up to 10,846 cervical cancers, 4,753 noncervical cancers among men, and 4,128 noncervical cancers among women are potentially attributable to HPV infection. Incidence rates for cervical cancer have declined significantly during the past 30 years in the United States, consistent with the success of Pap smear screening. However, incidence rates for anal, oropharyngeal, and vulvar cancers have increased substantially in recent years. The high proportion of cervical and noncervical cancers caused by HPV types 16 and 18, that is, 70%-76% for cervical cancers and 63%-95% for noncervical cancers, underscores the potential for prevention of a majority of cervical as well as noncervical HPV related cancers through prophylactic HPV vaccination. PMID- 20307843 TI - Preface. PMID- 20307842 TI - Examining the development and sexual behavior of adolescent males. AB - A careful examination of young men's sexuality by health professionals in pediatrics, primary care, and reproductive health is foundational to adolescent male sexual health and healthy development. Through a review of existing published data, this article provides background and a developmental framework for sexual health services for adolescent boys. The article first defines and provides an overview of adolescent boys' sexual health, and then discusses developmentally focused research on the following topics: (1) early romantic relationships and the evolution of power and influence within these relationships; (2) developmental "readiness" for sex and curiosity; (3) boys' need for closeness and intimacy; (4) adopting codes of masculinity; (5) boys' communicating about sex; and (6) contextual influences from peers, families, and providers. This article concludes by examining the implications of these data for sexual health promotion efforts for adolescent males, including human papillomavirus vaccination. PMID- 20307844 TI - What is new in radiology and pathology of motility disorders in children? AB - Disorders affecting colorectal motility lead to significant morbidity in children with surgical conditions. Etiology is frequently unknown, which in turn makes treatment empiric and compromises outcome. A thorough understanding of the normal mechanisms of control and the ability to recognize and manage defects is an important goal for clinicians. This article reviews recent advances made in the investigation of children with colorectal motility disorders, including the role of transit studies (marker studies and scintigraphy), options for assessing anatomy (ultrasound, contrast enema, and sectional imaging) and the use of manometry, both anorectal and colonic. Current concepts in microscopic evaluation are outlined. PMID- 20307845 TI - Advances in pediatric colorectal surgical techniques. AB - The operative management of pediatric colorectal diseases has improved significantly in recent years through the development of innovative approaches for operative exposure and a better understanding of colorectal anatomy. Advances in transanal and minimal access techniques have formed the cornerstone of this innovation, leading to improved functional outcomes, earlier recovery, and superior cosmetic results for a number of colorectal diseases. In this regard, we have witnessed a significant evolution in the way that many of these conditions are managed, particularly in the areas of anorectal malformations and Hirschsprung disease. Furthermore, a more thorough understanding of the pathophysiology underlying encopresis and true fecal continence has led to novel and less invasive approaches to the operative management of these conditions. The goal of this review is to describe the evolution of operative management pertaining to these diseases, with an emphasis on technical aspects and relevant clinical pitfalls. PMID- 20307846 TI - Transanal endorectal pull-through for Hirschsprung disease: technique, controversies, pearls, pitfalls, and an organized approach to the management of postoperative obstructive symptoms. AB - The transanal endorectal pull-through emerged in the late 1990s as the most recent step in the evolution of the surgical correction of Hirschsprung disease. This operation provides the advantages of a minimal access approach with shorter hospital stay, shorter time to full feeding, less pain, and improved cosmesis with excellent outcomes. This article will review the technical principles of the transanal endorectal pull-through, and will address ongoing controversies in the application of this technique. We will also discuss an organized approach to the problem of obstructive symptoms that may affect a subgroup of patients after the transanal pull-through. PMID- 20307847 TI - Genetics of Hirschsprung disease and anorectal malformations. AB - Hirschsprung disease (HD) and anorectal malformations (ARMs) result from alterations in hindgut development. It has long been recognized that both recur in families and thus result, at least in part, from genetic factors. Progress in the understanding of the genetic basis of HD has been made by the application of findings from genetic animal models of altered enteric nervous system development to human beings. Several genes have been shown to be important for human enteric nervous system development, and current work is progressing to identify genetic interactions that may explain the variable phenotype of HD. By contrast, understanding of the genetic factors underlying ARMs is much less developed. We and others have shown that genetic factors play an important role in the pathogenesis of ARMs, and many mouse genetic models suggest molecular pathways that may be altered in ARMs. PMID- 20307848 TI - Caring for children with colorectal disease in the context of limited resources. AB - The management of patients with colorectal disease in the pediatric population is challenging. Such management is all the more challenging when facing the constraints imposed by an environment with limited clinical resources. Three types of colorectal problems are highlighted in this article: anorectal malformations, Hirschsprung's disease, and acquired rectovaginal fistula in the human immunodeficiency virus-positive population. Through the use of illustrative cases, the authors discuss the pitfalls and challenges encountered in the diagnosis, treatment, and appropriate disposition of these patients. The bulk of the experience used to write this article was acquired in low- and middle-income countries in Africa. The authors hope that the lessons learned will help others manage such patients in the context of limited resources, but recognize that challenges will vary from place to place. There is no substitute for local, contextual expertise. PMID- 20307849 TI - Cloacal malformations: lessons learned from 490 cases. AB - In this review we describe lessons learned from the authors' series of patients born with the most complex of congenital anorectal problems, cloacal malformations, with the hope to convey the improved understanding and surgical treatment of the condition's wide spectrum of complexity learned from patients cared for over the last 25 years. This includes a series of 490 patients, 397 of whom underwent primary operations, and 93 who underwent reoperations after attempted repairs at other institutions. With regard to the newborn, we have learned that the clinician must make an accurate neonatal diagnosis, drain a hydrocolpos when present, and create an adequate, totally diverting colostomy, leaving enough distal colon available for the pull-through, and a vaginal replacement if needed. A correct diagnosis will avoid repairing only the rectal component. For the definitive reconstruction, all patients in the series were managed with a posterior sagittal approach; 184 of whom also required a laparotomy. The average length of the common channel was 4.6 cm for patients who required a laparotomy and 2.5 cm for those who did not. Hydrocolpos was present in 139 patients (30%). Vaginal reconstruction involved a vaginal pull-through in 308 patients, a vaginal flap in 44, vaginal switch in 48, and vaginal replacement in 90 (33 with rectum, 15 with colon, and 42 with small bowel). A total of 220 underwent total urogenital mobilization, which was first introduced in 1996. Complications included rectal prolapse in 26, vaginal stricture or atresia in 18, urethrovaginal fistula in 13, and urethral atresia in 6. A total of 53% of all cases have voluntary bowel movements. The others are kept clean with a mechanical daily emptying (an enema) as part of a bowel management program. Indications for reoperations included persistent urogenital sinus after initial repair in 39 patients. Fifty-one had problems such as rectal prolapse, stricture, retraction, dehiscence or atresia, 29 had a mislocated rectum, 34 had vaginal stricture, retraction, dehiscence, atresia, or stenosis, 16 had urethrovaginal or rectovaginal fistulae, and 5 had urethral stricture or atresia. The series was divided into 2 distinct groups of patients where common channel measurement was known (n = 400): group A were those with a common channel < or = 3.0 cm (n = 225, 56%) and group B had a common channel >3 cm (n = 175, 44%). The separation into these 2 groups has important therapeutic and prognostic implications. Patients in Group A can be repaired posterior sagittally with a reproducible operation. Because they represent most patients, most well-trained pediatric surgeons should be able to repair these types of malformations, and the prognosis is good. Patients in Group B (those with a common channel >3 cm), usually require a laparotomy, have a much higher incidence of associated urological problems, and often require special maneuvers for vaginal reconstruction. Surgeons who repair Group B malformations require special training in urology; the operations are prolonged and technically demanding, and the functional results are not as good as in group A. PMID- 20307850 TI - Gynecologic concerns in patients with anorectal malformations. AB - Children with anorectal malformations (ARMs) constitute a significant group within a pediatric surgery practice. In females, the most common ARM is an imperforate anus with a rectovestibular fistula, followed by an imperforate anus with a rectoperineal fistula and then cloacal anomalies. Some malformations, such as an imperforate anus with a rectovestibular fistula, may seem straightforward, treated with a posterior sagittal anorectoplasty; however, it is vital to recognize the association with gynecologic anomalies. Girls with the most complex anorectal defect, cloacal malformation, have significant associated urological and gynecologic anomalies, which should be recognized and treated. An opportunity to diagnose and treat such anomalies may be missed in the newborn period or at the definitive surgery, unless the pediatric surgeon is aware of this association. With the knowledge of the associated anomalies and long-term sequelae, surgeons can provide better care for girls and important counseling for parents. Important gynecologic issues to consider may be divided into several categories, such as infancy, puberty, sexual intimacy, and obstetrical concerns. Knowledge of reproductive-related issues in females with ARMs allows the pediatric surgeon and their gynecology colleagues to provide optimal surgical management throughout infancy, childhood, and into young adulthood. Appropriate counseling for patients and families about potential reproductive concerns that may develop many years after the definitive surgical repair allows preparation and planning to preserve future fertility. PMID- 20307851 TI - Evaluation and treatment of the patient with Hirschsprung disease who is not doing well after a pull-through procedure. AB - Ideally, after operative management of Hirschsprung disease, a child should thrive, avoid recurrent episodes of abdominal distention and enterocolitis, and be fecally continent. However, there is a small group of patients that do not do well after their pull-through procedure. The purpose of this article is to describe our algorithm for the work-up and management of the post pull-through patient with Hirschsprung disease who is not doing well. These children can be categorized into 2 distinct groups: (1) those who are soiling, and (2) those who suffer from distention and enterocolitis. Both of these patient types can be systematically treated with a combination of bowel management, dietary changes, and laxatives, and, potentially, a redo operation, with the goal of having a clean, and happy child. PMID- 20307852 TI - A practical approach to the management of pediatric fecal incontinence. AB - We describe the rationale and key aspects for success of a bowel management program for the treatment of pediatric fecal incontinence. A retrospective review was done of the medical strategies used for the treatment of over a 1000 patients with fecal incontinent, combining the experience of the authors' previously published reports (Pena A, Guardino K, Tovilla JM, et al. J Pediatr Surg 1998; 33:133-137 and Bischoff A, Levitt MA, Bauer C, et al. J Pediatr Surg 2009; 44:1278-1284) and additional treated patients after those publications. Emphasis was placed on the review of the key factors needed to achieve success. Through the years, we have learned important lessons that resulted in our current strategy which allows us to obtain better results than earlier in our series. At present, the key aspects for success are (a) to distinguish between true fecal incontinence and pseudoincontinence; (b) to determine the characteristics of the colon (dilated or nondilated), ascertained by looking at the patient's contrast enema, and determine the treatment strategy from this; (c) to monitor the result of the enema (amount of stool left in the colon) with daily abdominal radiographs during a 1-week period; and (d) to thereby modify the type of enema daily, depending on the clinical result, and the abdominal radiograph. Following a systematic rationale in the classification of patients with fecal incontinence and applying selectively, individualized management, it is possible to achieve a 95% success rate in patients suffering from fecal incontinence. PMID- 20307853 TI - Outcome of anorectal malformations and Hirschsprung's disease beyond childhood. AB - Anorectal malformations (ARMs) and Hirschsprung disease (HD) are the most common congenital colorectal defects in the newborn. The outcomes of HD and ARMs have improved significantly because of improved understanding of the pathologic anatomy and physiology of these defects and of the modern surgical techniques. Still, many patients suffer from defective bowel control even as adults. Some of these also have problems with urinary control and sexual functions. The functional problems are more pronounced in patients with ARMs. Compared with healthy people, both patients with ARMs and those with HD have limitations in their quality of life. Inferior quality of life is more common in patients with ARMs. There are very few published data on long-term outcome of adults with ARMs and HD. The effect of aging on the functional outcome and quality of life remains unclear, although some preliminary data suggest that the bowel function and quality of life may deteriorate with aging. PMID- 20307855 TI - Introduction. The World Society for Pediatric and Congenital Heart Surgery. PMID- 20307856 TI - Congenital heart surgery databases around the world: do we need a global database? AB - The question posed in the title of this article is: "Congenital Heart Surgery Databases Around the World: Do We Need a Global Database?" The answer to this question is "Yes and No"! Yes--we need to create a global database to track the outcomes of patients with pediatric and congenital heart disease. No--we do not need to create a new "global database." Instead, we need to create a platform that allows for the linkage of currently existing continental subspecialty databases (and continental subspecialty databases that might be created in the future) that will allow for the seamless sharing of multi-institutional longitudinal data across temporal, geographical, and subspecialty boundaries. This review article will achieve the following objectives: (A) Consider the current state of analysis of outcomes of treatments for patients with congenitally malformed hearts. (B) Present some principles that might make it possible to achieve life-long longitudinal monitoring and follow-up. (C) Describe the rationale for the creation of a Global Federated Multispecialty Congenital Heart Disease Database. (D) Propose a methodology for the creation of a Global Federated Multispecialty Congenital Heart Disease Database that is based on linking together currently existing databases without creating a new database. To perform meaningful multi-institutional analyses, any database must incorporate the following six essential elements: (1) Use of a common language and nomenclature. (2) Use of a database with an established uniform core dataset for collection of information. (3) Incorporation of a mechanism to evaluate the complexity of cases. (4) Implementation of a mechanism to assure and verify the completeness and accuracy of the data collected. (5) Collaboration between medical and surgical subspecialties. (6) Standardization of protocols for life long longitudinal follow-up. Analysis of outcomes must move beyond recording 30 day or hospital mortality, and encompass longer-term follow-up, including cardiac and non-cardiac morbidities, and importantly, those morbidities impacting health related quality of life. Methodologies must be implemented in our databases to allow uniform, protocol-driven, and meaningful long-term follow-up. We need to create a platform that allows for the linkage of currently existing continental subspecialty databases (and continental subspecialty databases that might be created in the future) that will allow for the seamless sharing of multi institutional longitudinal data across temporal, geographical, and subspecialty boundaries. This "Global Federated Multispecialty Congenital Heart Disease Database" will not be a new database, but will be a platform that effortlessly links multiple databases and maintains the integrity of these extant databases. Description of outcomes requires true multi-disciplinary involvement, and should include surgeons, cardiologists, anesthesiologists, intensivists, perfusionists, neurologists, educators, primary care physicians, nurses, and physical therapists. Outcomes should determine primary therapy, and as such must be monitored life-long. The relatively small numbers of patients with congenitally malformed hearts requires multi-institutional cooperation to accomplish these goals. The creation of a Global Federated Multispecialty Congenital Heart Disease Database that links extant databases from pediatric cardiology, pediatric cardiac surgery, pediatric cardiac anesthesia, and pediatric critical care will create a platform for improving patient care, research, and teaching related to patients with congenital and pediatric cardiac disease. PMID- 20307857 TI - The IMPACT registry: IMproving Pediatric and Adult Congenital Treatments. AB - Tremendous advances have occurred in catheter-based interventions for congenital heart disease. Multicenter trials of these advances are either out of date or have been limited in scope. As such little is known on the application of these techniques in the current era. The IMPACT Registry (IMproving Pediatric and Adult Congenital Treatments) will allow us to measure variability in the performance and outcomes of both diagnostic and interventional cardiac catheterization procedures in all children and adults with congenital heart disease. The IMPACT Registry will be harmonized with the Society of Thoracic Surgeons Congenital Heart Disease Database, thereby allowing us to compare catheter-based interventions with surgical interventions when appropriate. The initial release of the registry will only include hospital-based outcomes, but ultimately it will transition to a longitudinal registry. The IMPACT Registry will provide the necessary benchmark tools for quality improvement activities for cardiac catheterization procedures in congenital heart disease. PMID- 20307858 TI - The challenge of congenital heart disease worldwide: epidemiologic and demographic facts. AB - Congenital heart disease (CHD) afflicts a large number of children every year. The incidence of CHD is generally considered to be 8 per 1,000 live births. However, this estimate is perhaps inaccurate and does not take into consideration regional differences. A large review of the literature was performed to establish the true incidence of CHD and geographical variations. Data on the incidence of specific lesions and their geographical variation, as well as on mortality from CHD, was also reviewed. Taking into consideration the available data on incidence, mortality, and access to care, the global challenge that CHD represents was analyzed. Insight into how to confront this challenge is given. PMID- 20307859 TI - Improving pediatric cardiac surgical care in developing countries: matching resources to needs. AB - This article reviews a systematic approach to the design and support of pediatric cardiac surgery programs in the developing world with the guidance and strategies of Children's HeartLink, an experienced non-government organization for more than 40 years. An algorithm with criteria for the selection of a partner site is outlined. A comprehensive education strategy from the physician to the allied health care provider is the mainstay for successful program development. In a partner program, the road to successful advancement and change depends on many factors, such as government support, hospital administration support, medical staff leadership, and a committed and motivated faculty with requisite skills, incentives, and resources. In addition to these factors, it is essential that the development effort includes considerations of environment (eg, governmental support, regulatory environment, and social structure) and health system (elements related to affordability, access, and awareness of care) that impact success. Partner programs should be willing to initiate a clinical database with the intent to analyze and critique their results to optimize quality assurance and improve outcomes. PMID- 20307860 TI - Pro: NIRS is "standard of care" for postoperative management. AB - Successful postoperative management depends on early detection and correction of circulatory insufficiency. Global cardiac output and oxygen delivery must be adequate and distributed appropriately to meet metabolic demands to prevent the development of multi-organ dysfunction, morbidity, and death. Decreased cardiac output during the postoperative period is common, but circulatory assessment using standard monitoring provides inadequate information to reliably detect low cardiac output syndrome or effectively guide therapy. Goal-directed therapy using invasive estimates of global oxygen supply-demand balance (SvO2) has been shown to improve survival among patients in shock states. Near infrared spectroscopy (NIRS) is a noninvasive assessment of regional oxygen supply-demand balance. Multiple prospective observational studies have shown that NIRS-derived measures of systemic oxygen balance correlate with global circulatory measures, including SvO2 and biochemical indicators of shock. Additionally, NIRS has been shown in multiple prospective observational studies to identify circulatory inadequacy in specific organ systems, such as the brain, kidney, and gut. NIRS provides continuous, non-invasive measures that are suitable targets for goal-directed therapy to treat deficiencies in global and regional perfusion and should be standard of care. PMID- 20307861 TI - Near infrared spectroscopy (NIRS) should not be standard of care for postoperative management. AB - Neurologic dysfunction is a problem in patients with congenital heart disease. Near infrared spectroscopy (NIRS) may provide a real-time window into cerebral oxygenation. Enthusiasm for NIRS has increased in hopes of reducing neurologic dysfunction. However, potential gains need to be evaluated relative to cost and potential detriment of intervention before routine implementation. Responding to data in ways that seem intuitively beneficial can be risky when the long-term impact is unknown. Many centers, and even entire countries, have adopted NIRS as standard of care. Available data suggest that multimodality monitoring, including NIRS, may be a useful adjunct. However, the current literature on the use of NIRS alone does not demonstrate improvement in neurologic outcome. Data correlating NIRS findings with indirect measures of neurologic outcome or mortality are limited. Although NIRS has promise for measuring regional tissue oxygen saturation, the lack of data demonstrating improved outcomes limits the support for wide-spread implementation. PMID- 20307862 TI - Use of a fenestration should be routine during the Fontan procedure: PRO. AB - The physiologic effects of a fenestration are to decrease "Fontan pressure" and systemic oxygen saturation, but to improve both cardiac index and systemic oxygen delivery. Several nonrandomized studies have shown that a fenestration improves clinical outcomes by decreasing the duration of postoperative effusions and the length of hospital stay. The single prospective, randomized study has also shown that use of a fenestration improves clinical outcomes. While there are some disadvantages to a fenestration; these are of relatively limited clinical importance. Selective rather than routine use of a fenestration relies on the ability to predict outcome based on preoperative or intraoperative variables. However, none of these variables has been found to have useful predictive value in the individual patient. In conclusion, the Fontan procedure can be done without a fenestration, with good outcomes. However, the positive effects of a fenestration on duration of effusions and length of hospital stay argue that use of a fenestration should be routine during the Fontan procedure. PMID- 20307863 TI - Aortic valve repair for congenital and balloon-induced aortic regurgitation. AB - Current techniques for aortic valve replacement in the child carry multiple disadvantages. Longer-term follow-up of the Ross procedure has documented disappointing late results for an increasing proportion of patients. Many challenges continue to face the development of a tissue-engineered valve with growth potential. In this setting, aortic valve repair is a useful temporizing procedure that allows a child to have an excellent quality of life, free from the need for anticoagulation and the risk of thromboembolism. Repair techniques are primarily based on the use of autologous pericardium to extend leaflets and support prolapsing leaflets. These methods appear to be particularly applicable in the setting of balloon-induced aortic valve regurgitation. An increasing number of centers are reporting satisfactory midterm results with aortic valve repair. PMID- 20307864 TI - Uses and limitations of registry and academic databases. AB - A database is simply a structured collection of information. A clinical database may be a Registry (a limited amount of data for every patient undergoing heart surgery) or Academic (an organized and extensive dataset of an inception cohort of carefully selected subset of patients). A registry and an academic database have different purposes and cost. The data to be collected for a database is defined by its purpose and the output reports required for achieving that purpose. A Registry's purpose is to ensure quality care, an Academic Database, to discover new knowledge through research. A database is only as good as the data it contains. Database personnel must be exceptionally committed and supported by clinical faculty. A system to routinely validate and verify data integrity is essential to ensure database utility. Frequent use of the database improves its accuracy. For congenital heart surgeons, routine use of a Registry Database is an essential component of clinical practice. PMID- 20307865 TI - The Congenital Heart Surgeons Society Datacenter: unique attributes as a research organization. AB - Over the last 25 years, the Congenital Heart Surgeons Society (CHSS) has evolved from an informal club to a mature organization. A central feature of the CHSS has been dedication to evaluating outcomes of congenital heart surgery across a wide array of clinical diagnoses. These research activities have been orchestrated through the CHSS Datacenter, which has developed a unique organizational structure that has strengths and weaknesses in comparison to other research organizational structures (e.g., prospective randomized trials, registries, etc). This review will highlight the unique attributes of the CHSS Datacenter with emphasis on the Datacenter's strengths and weaknesses in comparison to other organizational structures. PMID- 20307866 TI - Multi-institutional studies: lessons learned from the Pediatric Heart Network Single Ventricle Reconstruction Trial. AB - This session of the Congenital Post-Graduate Course 89th Annual Meeting of the American Association for Thoracic Surgery focused on clinical research in pediatric cardiac surgery. This particular lecture concentrated on the management of clinical trials from the viewpoint of a multi-institutional trial, utilizing my experiences as the Study Co-Chair of the National Heart Lung Blood Institute (NHLBI)-funded, Pediatric Heart Network Single Ventricle Reconstruction (SVR) Trial. Preparing for the role as a Primary Investigator through coursework and reading is an important prerequisite. Study design requires thoughtful crafting of the primary question, secondary question, and subanalyses. Often the challenge is not what to include, but what to exclude, to develop a practical database. Getting your co-investigators invested in the trial is crucial, as subject enrollment is time-consuming and will determine the success or failure of your trial. PMID- 20307867 TI - Chance, bias, and confounding: threats to valid measurement of quality in the context of pediatric cardiac surgery. AB - Assessment of quality in pediatric cardiac surgery has frequently been an add-on to efforts to measure adult cardiac surgery, without sufficient acknowledgement of the differences between the specialties. As a result, data reporting has often proceeded without adequate attention to data analysis. Assessment of clinical outcomes relies on the methods of observational epidemiology. Interpretation of the results of such investigations requires an understanding of the limitations inherent in the design of observational studies: chance, bias, and confounding. These limitations are of particular importance when studying pediatric cardiac surgery because of the relatively low number of cases performed at any one institution or by any one surgeon, the diversity of operations, and the heterogeneity of the congenital cardiac patient population. PMID- 20307868 TI - The Fontan/Kreutzer procedure at 40: an operation for the correction of tricuspid atresia. AB - The first atriopulmonary anastomosis (APA) with neither a valve in the inferior vena cava (IVC) nor an Glenn shunt was performed in 1971. A fenestration was intentionally left in the atrial septum. In a second patient, the APA incorporated the patient's own pulmonary valve, which had been removed from the outflow tract of the right ventricle. Since the early days, our rationale was that the right atrium would only function as a pathway, and the end diastolic pressure and the systole of the main ventricle would be the principal "pump" of this system. The late hemodynamic problems of the APA have decreased with newer and better surgical techniques, such as the lateral tunnel (LT) or the extracardiac conduit (EC). Although these procedures have improved the prognosis and quality of life of patients with a univentricular heart (UH), in the long run, deterioration frequently occurs because of chronic low cardiac output and high central venous pressure. Progressive increase in pulmonary vascular resistances and ventricular dysfunction are frequently the underlying reasons for this deterioration. However, such deterioration is not inevitable in every case, as shown in the longest survivor of the world after 34 years of follow-up. The Fontan Kreutzer (FK) palliation represents the best surgical option despite its uncertain late outcome. Certainly, it is one of the triumphs of cardiac surgery in congenital heart disease. PMID- 20307869 TI - Evolution of the Fontan-Kreutzer procedure. AB - The surgical techniques used to construct the Fontan-Kreutzer circulation have evolved considerably since the initial reports. In the early years, it was thought that a power source other than the main ventricular chamber was useful or even necessary to serve the pulmonary circulation. Better understanding of the physiology of the Fontan-Kreutzer circulation has led to an understanding that avoidance of flow disturbances and energy losses in the surgically constructed pathways is critically important. In vitro studies and clinical investigations of flow dynamics led to the introduction of the total cavopulmonary connection, or total cavopulmonary connections, designed to minimize flow disturbances and the resultant energy losses. Other important surgical modifications include staging with a superior cavopulmonary connection and creation of a fenestration. These innovations have resulted in extension of the Fontan-Kreutzer procedure to the management of complex univentricular hearts and, in particular, the management of hypoplastic left heart syndrome. There have been significant improvements of early mortality and morbidity following the Fontan-Kreutzer procedure. Yet it is important to recognize that there is continuing late attrition and morbidity for patients with the Fontan-Kreutzer circulation. PMID- 20307870 TI - Forty years of the Fontan operation: a failed strategy. PMID- 20307871 TI - [Laryngotracheal NK/T lymphoma: clinical case]. AB - NK/T-cell lymphoma is a rare condition with an aggressive course and poor prognosis. Historically known as "lethal midline granuloma", it generally appears in a midfacial location. We describe the case of a 22-year-old Colombian woman with laryngotracheal affectation, presenting with hoarseness and hemoptysis. CT scan and MRI showed severe laryngeal and tracheal destruction. The biopsy showed a polymorphic, lymphoid cell infiltrate with angiocentric and angiodestructive pattern. The immunohistochemical study confirmed the immunophenotype of the NK/T cells: CD2+, CD56+ and cytoplasmic CD3+. The in situ hybridization and flow cytometry findings were: EBER+, TIA-1+ and perforin+. The patient died from complications of her disease, before undergoing oncologic treatment. PMID- 20307873 TI - Effects of organosolv pretreatment and enzymatic hydrolysis on cellulose structure and crystallinity in Loblolly pine. AB - Ethanol organosolv pretreatment was performed on Loblolly pine to enhance the efficiency of enzymatic hydrolysis of cellulose to glucose. Solid-state (13)C NMR spectroscopy coupled with line shape analysis was used to determine the structure and crystallinity of cellulose isolated from pretreated and enzyme-hydrolyzed Loblolly pine. The results indicate reduced crystallinity of the cellulose following the organosolv pretreatment, which renders the substrate easily hydrolyzable by cellulase. The degree of crystallinity increases and the relative proportion of para-crystalline and amorphous cellulose decreases after enzymatic hydrolysis, indicating preferential hydrolysis of these regions by cellulase. The structural and compositional changes in this material resulting from the organosolv pretreatment and cellulase enzyme hydrolysis of the pretreated wood were studied with solid-state CP/MAS (13)C NMR spectroscopy. NMR spectra of the solid material before and after the treatments show that hemicelluloses and lignin are degraded during the organosolv pretreatment. PMID- 20307872 TI - [Sphenoid sinusitis with intracranial extension produced by an emergent fungus]. AB - This is a case of fungal sphenoid sinusitis in a diabetic patient with non specific symptoms and bone erosion radiological findings in the superior and posterior sphenoid walls. Surgical treatment was performed by transnasal endoscopic approach and voriconazole orally thereafter. The histopathological study found fungus hyphal without mucosa invasion and the molecular study determined DNA to be Phialemonium curvatum, an unusual pathogen. PMID- 20307874 TI - Preliminary studies into the inhibition of the cholesterol alpha glucosyltransferase from Helicobacter pylori using azasugars. AB - Various known inhibitors of glycosidases were assessed for their ability to inhibit, both independently as well as with UDP, the cholesterol alpha glucosyltransferase from Helicobacter pylori. The sub-cloning, expression and purification of the glucosyltransferase is also discussed. PMID- 20307875 TI - Immunoregulation of autocrine prolactin: suppressing the expression of costimulatory molecules and cytokines in T lymphocytes by prolactin receptor knockdown. AB - Ample evidence indicates that prolactin (PRL) secreted from the pituitary gland plays an important role in a variety of human immune responses. However, the immunoregulation of autocrine PRL in T lymphocytes is not fully understood. To evaluate the role of autocrine PRL in T lymphocyte activation, PRL receptor (PRLR) in Jurkat cells was silenced by lentivirus-mediated stable expression of PRLR shRNAi. Knockdown of PRLR resulted in a considerable reduction of phytohemagglutinin (PHA)-induced T cell proliferation. Moreover, the synthesis and secretion of CD137, CD154, IL-2 and IL-4 were significantly decreased, while the production of CD28, IFN-gamma and IL-10 was not affected in PHA-primed PRLR deficient cells. These results demonstrate the importance of autocrine regulation of the PRL signaling in T lymphocyte growth and activation, and support a mechanism by which autocrine PRL participates in the immunoregulation through selectively influencing the expression of certain critical costimulatory molecules and cytokines. PMID- 20307876 TI - Toxicity of chromated copper arsenate: a study in mice. AB - Chromated copper arsenate (CCA) was widespread used as a chemical wood preservative with application in the construction of playground equipment, fences, jetties, and naval. Environmental protection agency (EPA) had limited the use of CCA-treated wood on 2002, due to probable implications on both human and environmental health. Although this fact, several industries pursue the use of this product within their manufactories. In addition, the durability of this wood for 60 years, makes these treated products an hazard to the public health. In the present work, studies were explored exposing mice to CCA, during 14, 24, 48, and 96 h for the assessment of acute toxicity of CCA. Kidney and liver were removed, prepared for histology and for metalloid, and copper content evaluation by high resolution inductively coupled plasma mass spectroscopy. The histological results evidenced apparently normal structures for control animals and group exposed to As2O5. On the contrary, the renal sections of the animals treated with CCA revealed epithelium cells desquamation, hyaline, and granular casts in renal tubules lumen. Furthermore, high levels of arsenic were detected in the kidney of animals treated with CCA over 14 and 48 h, being significantly greater than controls. Although this approach underlines the potential hazard of CCA on some vital organs, further testing may be required to establish the impacts on other functions. PMID- 20307877 TI - [Adult-onset hereditary hemophagocytic lymphohistiocytosis]. PMID- 20307878 TI - Endogenous gonadotropin flare following microdose leuprolide (MDL) stimulation protocol does not correlate with in vitro fertilization (IVF) outcome. AB - Patients undergoing first IVF cycle using MDL from October 2005 to November 2008 had serum FSH, LH, and estradiol (E2) levels measured prior to and 2 days after initiation of MDL; and evidence of a follicular flare, defined as a doubling in endogenous gonadotropins, was evaluated and correlated with clinical pregnancy, cancellation, implantation, spontaneous abortion, and ongoing pregnancy rate as well as cycle parameters. Although there was no difference in IVF outcomes, higher doses of exogeneous gonadotropins as well as greater days of stimulation were observed in patients with a documented FSH or LH flare. PMID- 20307879 TI - Estrogens and androgens affect human luteal cell function. AB - OBJECTIVE: To evaluate estrogens (Es)--E2, estrone (E1), and estriol--and androgens--T and androstendione (A)-effect on P, prostaglandin (PG) F2alpha, PGE2, and vascular endothelial growth factor (VEGF) release and on VEGF expression in human luteal cells. To elucidate whether androgens effects were direct or mediated by their conversion in Es, an aromatase inhibitor was used. Finally, the luteal effect of the non-aromatizable dihydrotestosterone was evaluated. DESIGN: Prospective laboratory study. SETTING: University hospital. PATIENT(S): Corpora lutea (CLs) were obtained from 36 normally menstruating patients in the midluteal phase of the menstrual cycle. INTERVENTION(S): The human luteal cells were isolated from CLs and primary cultures were established. MAIN OUTCOME MEASURE(S): P and PG release were assayed by enzyme immunoassay; VEGF secretion by ELISA; VEGF messenger RNA (mRNA) expression by real-time polymerase chain reaction (PCR). RESULT(S): P and PGF2alpha secretion were decreased by Es and androgens. The VEGF release was increased by Es and androgens, whereas VEGF mRNA expression was not. The aromatase inhibitor counteracted T and A luteal effects. CONCLUSION(S): Both Es and androgens could participate in the regulation of human luteal function. The effect of T and A seems to be mediated by their conversion to Es, whereas for dihydrotestosterone, both direct androgenic and indirect estrogenic luteal effects could coexist. PMID- 20307880 TI - Internal consistency and Cronbach's alpha: A comment on Beeckman et al. (2010). PMID- 20307881 TI - Is epicardial fat tissue a marker of metabolic syndrome in obese children? AB - OBJECTIVE: The goal of the study was to assess the association between epicardial fat (EF) thickness and waist circumference, insulin resistance and other metabolic syndrome components in obese children. METHODS: 52 obese children (23 males and 29 females) in the mean age 11.6 + or - 2.87 years were studied. Their mean BMI was 26.17 + or - 2.13. Control group included 54 normal weight children (22 males and 32 females) in the mean age 12.85 + or - 2.15 years (BMI -18.55 + or - 2.71). Obesity was defined according to IOTF criteria. EF thickness on the right ventricle was obtained in all children by two-dimensional M-mode echocardiogram. In obese children systolic (SBP) and diastolic (DBP) blood pressure was measured and fasting serum triglycerides, low- and high-density lipoproteins, cholesterol, and glucose and insulin levels were measured. Metabolic syndrome was determined according to IDF 2007 criteria. RESULTS: We documented a statistically significant correlation between epicardial fat BMI z score and waist circumference in both groups. No statistically significant correlation between EF thickness and HOMA Index was found. There was also no statistically significant difference in EF thickness between obese children with or without metabolic syndrome. CONCLUSION: Although EF in overweight children is a good indicator of visceral fat it does not seem to be the independent predictor of metabolic syndrome in this age group. The lack of relationship of EF thickness with insulin resistance and metabolic syndrome suggests that in children the prognostic value of this fat tissue may differ from that in adults. PMID- 20307882 TI - Impact of apolipoprotein E genotype and dietary quercetin on paraoxonase 1 status in apoE3 and apoE4 transgenic mice. AB - OBJECTIVES: The aim of the present study was to determine hepatic paraoxonase 1 (PON1) status in response to apoE genotype and dietary quercetin supplementation in mice. METHODS AND RESULTS: ApoE3 and apoE4 transgenic mice were fed semi synthetic diets without (controls) and with quercetin (2 mg/g diet) for 6 weeks. Hepatic mRNA and protein levels of PON1 were significantly lower in apoE4 as compared to apoE3 mice. Feeding quercetin-enriched diets induced hepatic PON1 gene expression with a tendency for greater induction in apoE3 as compared to apoE4 mice. Furthermore, hepatic mRNA and protein levels of beta-glucuronidase and sulfatase, both enzymes centrally involved in the deconjugation of quercetin conjugates, were lower in apoE4 vs. apoE3 mice. PPARgamma (which partly controls PON1 gene expression) mRNA levels were lower in apoE4 vs. apoE3 mice. CONCLUSION: We provide first evidence that PON1 is differentially regulated in response to apoE genotype. PMID- 20307883 TI - Eosinophil cationic protein: A new biomarker of coronary atherosclerosis. AB - AIMS: Coronary atherosclerosis is a chronic inflammatory disease, but different inflammatory biomarkers may reflect different phases of atherosclerotic plaque evolution. We aimed at assessing the role of eosinophil cationic protein (ECP), a sensitive marker of eosinophil activation, and C-reactive protein (CRP) in coronary artery disease (CAD). METHODS AND RESULTS: Consecutive anginal patients with angiographic evidence of CAD [stable angina (SA) or non-ST-elevation acute coronary syndrome (NSTE-ACS)], or with angiographically normal coronary arteries (NCA) were enrolled. The severity of CAD was graded according to Bogaty's score and coronary lesion morphology was defined as smooth or complex. Baseline ECP and high sensitivity CRP were measured in all patients. Of 198 patients (64 + or - 10 years, male 74%), 91 had SA, 57 had NSTE-ACS and 50 had NCA. ECP levels were significantly higher in SA [30 microg/L (13.8-46.9), p<0.001] and NSTE-ACS [21.8 microg/L (5.5-46.3), p=0.016] compared to NCA [9.7 microg/L (6.1-13.6)], without significant difference between SA and NSTE-ACS (p=0.45). CRP levels were significantly higher in NSTE-ACS [2.38 mg/L (1.11-11.94)] compared to SA [1.48 mg/L (0.82-2.83), p=0.03], and NCA [1.09 mg/L (0.8-2.1), p<0.001], without significant difference between SA and NCA (p=0.20). The addition of ECP to main cardiovascular risk factors improved the area under the curve from 0.88 to 0.92, p=0.007 for the angiographic diagnosis of CAD; further addition of CRP increased the area to 0.94, p=0.014. At multiple linear regression analysis ECP levels independently predicted CAD severity (p=0.001), whereas CRP levels independently predicted lesion complexity (p=0.01). CONCLUSIONS: Our study shows that ECP is a marker of CAD and that different inflammatory biomarkers reflect different phases of atherosclerotic plaque evolution. PMID- 20307884 TI - The adsorption of Naproxen enantiomers on the chiral stationary phase (R,R)-Whelk O1 under reversed-phase conditions: the effect of mobile phase composition. AB - The adsorption of the Naproxen enantiomers on the Whelk-O1 chiral stationary phase from acidic (0.01 M CH3COOH) methanol-water solutions was studied using the frontal analysis method and band profile calculations. The adsorption model that best accounted for these data is one assuming the coexistence of three types of adsorption sites, two of them being enantioselective, associated with the chiral selectors, the third type being the nonselective type of sites associated with residual surface silanol groups. The adsorption equilibrium is influenced by secondary processes that result in variations of the model parameters with the mobile phase composition. Several qualitative correlations between the model parameters and the methanol-water ratio were observed and are discussed. PMID- 20307885 TI - Investigations on the emission of fragrance allergens from scented toys by means of headspace solid-phase microextraction gas chromatography-mass spectrometry. AB - In the revised European toy safety directive 2009/48/EC the application of fragrance allergens in children's toys is restricted. The focus of the present work lies on the instrumental analytics of 13 banned fragrance allergens, as well as on 11 fragrance allergens that require declaration when concentrations surpass 100 microg per gram material. Applying a mixture of ethyl acetate and toluene solid/liquid extraction was performed prior to quantitative analysis of mass contents of fragrances in scented toys. In addition, an easy-to-perform method for the determination of emitted fragrances at 23 degrees C (handling conditions) or at 40 degrees C (worst case scenario) has been worked out to allow for the evaluation of potential risks originating from inhalation of these compounds during handling of or playing with toys. For this purpose a headspace solid-phase microextraction (HS-SPME) technique was developed and coupled to subsequent gas chromatography-mass spectrometry (GC-MS) analysis. Fragrance allergens were adsorbed (extracted) from the gas phase onto an 85 microm polyacrylate fiber while incubating pieces of the scented toys in sealed headspace vials at 23 degrees C and 40 degrees C. Quantification of compounds was performed via external calibration. The newly developed headspace method was subsequently applied to five perfumed toys. As expected, the emission of fragrance allergens from scented toys depends on the temperature and on the content of fragrance allergens present in those samples. In particular at conditions mimicking worst case (40 degrees C), fragrance allergens in toys may pose a risk to children since considerable amounts of compound might be absorbed by lung tissue via breathing of contaminated air. PMID- 20307886 TI - The kinetic plot method applied to gradient chromatography: theoretical framework and experimental validation. AB - The kinetic plot method, originally developed for isocratic separations, was extended to the practically much more relevant case of gradient elution separations. A set of explicit as well as implicit data transformation expressions has been established. These expressions can readily be implemented in any calculation spread-sheet program, and allow to directly turn any experimental data set representing the relation between the separation efficiency and the flow rate measured on a single column into the kinetic performance limit curve of the tested separation medium. Since the kinetic performance limit curve is based on an extrapolation to columns with a different length, it should be realized that the curve is only valid under the assumption that the gradient time and the delay time (if any) are adapted such that the analytes are subjected to the same relative mobile phase history when the column length is changed. Both experimental and numerical data are presented to corroborate the fact that the kinetic performance limit curves that are obtained using the proposed expressions are indeed independent of the column length the experimental data were collected in. Deviations might arise if excessive viscous heating occurs in columns with a pronounced non-adiabatic thermal behaviour. PMID- 20307887 TI - Fast proteomic protocol for biomarker fingerprinting in cancerous cells. AB - The advance of novel technologies that will enable the detection of large sets of biomarker proteins, to greatly improve the sensitivity and specificity of an assay, represents a major objective in biomedical research. To demonstrate the power of mass spectrometry (MS) detection for large-scale biomarker screening in cancer research, a simple, one-step approach for fast biomarker fingerprinting in complex cellular extracts is described. MCF-7 breast cancer cells were used as a model system. Fast proteomic profiling of whole cellular extracts was achieved on a linear trap quadrupole (LTQ) mass spectrometer by one of the following techniques: (a) data-dependent liquid chromatography (LC)-MS/MS of un-labeled cell extracts, (b) data-dependent LC-MS/MS with pulsed Q dissociation (PQD) detection of iTRAQ labeled samples, and (c) multiple reaction monitoring (MRM)-MS of low abundant proteins that could not be detected with data-dependent MS/MS. The data-dependent LC-MS/MS analysis of MCF-7 cells enabled the identification of 796 proteins (p<0.001) and the simultaneous detection of 156 previously reported putative cancer biomarkers. PQD detection of iTRAQ labeled cells resulted in the detection of 389 proteins and 64 putative biomarkers. MRM-MS analysis enabled the successful monitoring of a panel of low-abundance proteins in one single experiment, highlighting the utility of this technique for targeted analysis in cancer investigations. These results demonstrate that MS-based technologies relying on a one-step separation protocol have the potential to revolutionize biomarker research and screening applications by enabling fast, sensitive and reliable detection of large panels of putative biomarkers. To further stimulate the exploration of proteins that have been previously reported in the literature to be differentially expressed in a variety of cancers, an extensive list of approximately 1100 candidate biomarkers has been compiled and included in the manuscript. PMID- 20307888 TI - Comprehensive blood plasma lipidomics by liquid chromatography/quadrupole time-of flight mass spectrometry. AB - A lipidomics strategy, combining high resolution reversed-phase liquid chromatography (RPLC) with high resolution quadrupole time-of-flight mass spectrometry (QqTOF), is described. The method has carefully been assessed in both a qualitative and a quantitative fashion utilizing human blood plasma. The inherent low technical variability associated with the lipidomics method allows to measure 65% of the features with an intensity RSD value below 10%. Blood plasma lipid spike-in experiments demonstrate that relative concentration differences smaller than 25% can readily be revealed by means of a t-test. Utilizing an advanced identification strategy, it is shown that the detected features mainly originate from (lyso-)phospholipids, sphingolipids, mono-, di- and triacylglycerols and cholesterol esters. The high resolution offered by the up-front RPLC step further allows to discriminate various isomeric species associated with the different lipid classes. The added value of utilizing a Jetstream electrospray ionization (ESI) source over a regular ESI source in lipidomics is for the first time demonstrated. In addition, the application of ultra high performance LC (UHPLC) up to 1200bar to extend the peak capacity or increase productivity is discussed. PMID- 20307889 TI - Adsorption of arsenic ions on Brazilian sepiolite: effect of contact time, pH, concentration, and calorimetric investigation. AB - The original sepiolite clay mineral has been collected from Amazon region, Brazil. The compound 2-aminomethylpyridine (AMP) was anchored onto Amazon sepiolite surface by heterogeneous route. The natural (SPT) and modified (SPT(AMP)) sepiolite samples were characterized by elemental analysis, SEM, N(2) adsorption, and nuclear magnetic nuclei of (29)Si and (13)C. The well-defined peaks obtained in the (13)C NMR spectrum in the 0-160 ppm region confirmed the attachment of organic functional groups as pendant chains bonded into the porous clay. The ability of these materials to remove As(V) from aqueous solution was followed by a series of adsorption isotherms at room temperature and pH 4.0. The maximum number of moles adsorbed was determined to be 7.26*10(-2) and 11.70*10( 2) mmol g(-1) for SPT and SPT(AMP), respectively. In order to evaluate the clay samples as adsorbents in dynamic system, a glass column was fulfilled with clay samples (1.0 g) and it was fed with 2.0*10(-2) mmol dm(-3) As(V) at pH 4.0. The energetic effects caused by metal cations adsorption were determined through calorimetric titrations. Thermodynamics indicated the existence of favorable conditions for such As(V)-nitrogen interactions. PMID- 20307890 TI - Thermodynamic investigation of the systems poly(ethylene glycol) + sodium pentane 1-sulfonate + water and poly(vinyl pyrrolidone) + sodium pentane-1-sulfonate + water. AB - Thermodynamic properties for aqueous solutions containing sodium pentane-1 sulfonate (C(5)SO(3)Na) in the absence and presence of poly(ethyleneglycol) (PEG) or poly(vinylpyrrolidone) (PVP) determined as a function of surfactant concentration from the density, sound velocity, viscosity, conductivity and vapor liquid equilibria data, are reported here. Densities and sound velocities, allowing for the determination of apparent molar volumes and compressibilities, were measured at 288.15-313.15 K. Changes in the apparent molar properties upon micellization were derived using a pseudo-phase-transition approach and the infinite dilution apparent molar volumes and compressibilities of the monomer and micellar state of C(5)SO(3)Na in the investigated solutions were determined. The values of the infinite dilution apparent molar properties of micellar states of C(5)SO(3)Na in aqueous polymer solutions are larger than those in pure water. Vapor-liquid equilibrium data such as water activity, vapor pressure, osmotic coefficient, activity coefficient and Gibbs free energies were obtained through isopiestic method at 298.15 K. The variations of the critical micelle concentration (CMC) of C(5)SO(3)Na in water and in aqueous PEG and PVP solutions with temperature were obtained and a comparison between the CMC of C(5)SO(3)Na obtained from different thermodynamic properties was also made. PMID- 20307891 TI - Children's thinking about their own and others' regret and relief. AB - In two experiments using a decision-making game, we investigated children's thinking about regret and relief. In Experiment 1 (N=43, 31 children [5 years 4 months to 8 years 2 months of age] and 12 adults), participants chose between two boxes containing different numbers of stickers. They rated their happiness before learning that the other box contained more (regret) or fewer (relief) stickers. They rerated their chosen box with the counterfactual knowledge. The experience of regret was evident at 5 years of age, and the experience of relief was evident at 7 years of age. In Experiment 2 (N=69, 53 children [5 years 3 months to 6 years 11 months of age] and 16 adults), participants either played the game (self condition) or watched another play the game (other condition). Children in the self condition confirmed the results from Experiment 1. We found no evidence that children up to 7 years of age were able to predict others' regret and relief, a finding that suggests differing developmental trajectories between experiencing and understanding others' regret and relief. PMID- 20307893 TI - [Pancoast tumor with Horner's syndrome]. PMID- 20307892 TI - Depression is associated with increased sensitivity to signals of disgust: a functional magnetic resonance imaging study. AB - Emotions of fear and disgust are related to core symptoms of depression. The neurobiological mechanisms of these associations are poorly understood. This functional magnetic resonance imaging study aimed at examining the Blood oxygenation level dependent (BOLD) response to facial expressions of fear and disgust in patients with major depressive disorder. Nine patients in an episode of major depression and nine healthy controls underwent two functional magnetic resonance imaging experiments where they judged the gender of facial identities displaying different degrees (mild, strong) of fear or disgust, intermixed with non-emotional faces. Compared with healthy controls, patients with depression demonstrated greater activation in left insula, left orbito-frontal gyrus, left middle/inferior temporal gyrus, and right middle/inferior temporal gyrus to expressions of strong disgust. Depressed patients also demonstrated reduced activation in left inferior parietal lobe to mildly fearful faces. Enhanced activation to facial expressions of disgust may reflect an emotion processing bias that suggests high relevance of emotion of disgust to depression. PMID- 20307894 TI - [Erdheim-Chester disease with bone lesion and retroperitoneal fibrosis]. PMID- 20307895 TI - [Hospital care of patients with A/H1N1 influenza: evaluation of the first 1000 reported cases in Spain]. AB - INTRODUCTION AND OBJECTIVES: Influenza A is expected to have a great impact in countries in the northern hemisphere yet little has been reported about how this outbreak can affect hospital care. The aim of this study is to assess patients who demand care for flu symptoms and their outcome. MATERIAL AND METHODS: From the beginning of the outbreak a specific protocol was established for the care of patients with potential influenza A in admission, emergency and hospitalization ward. A nominal registry was designed with clinical and epidemiological data. RESULTS: 1018 patients were evaluated for potential influenza A from the beginning of the outbreak until the 31(st) August, 2009. 77% of them fulfilled clinical criteria and were classified as suspected cases. Mean age was 31,7 years (SD17,2), 52% were women, 3,3% pregnant or puerperal. The admission rate was 23,4% with a global mean stay of 3,5 days, and 2,5 for the adults who were admitted to the short stay hospital unit. 2,8 % had pneumonia, two patients required admission to the intensive care unit and one of them died. CONCLUSIONS: Our data show an outbreak with mild illness, with a remarkable percentage of pneumonia but with good outcome. Despite of the high percentage of admissions, and in order to avoid the misleading attention to other patients, we believe that an assistance model based in specific units, short stay and post-discharge follow up could be suitable. PMID- 20307896 TI - A simple pharmacokinetic model linking plasma progesterone concentrations with the hormone released from bovine intravaginal inserts. AB - On the basis of pharmacokinetic modeling, this study provides some insights into predicting in vivo plasma progesterone concentrations when using bovine intravaginal inserts for systemic progesterone delivery. More significantly, this contribution is the first attempt to build a simple pharmacokinetic model that links plasma progesterone concentrations with the hormone released from bovine intravaginal inserts. After evaluating three rival pharmacokinetic models and considering some phenomena involved in the intravaginal administration of progesterone, a primary pharmacokinetic model having a good data fitting capability with only two adjustable parameters is proposed to the above mentioned task. Kinetic parameters are given for lactating Holstein dairy cows with two levels of daily milk yields; and non-pregnant, non-lactating Holstein-Friesian cattle. Model predictions indicate the occurrence of a preferential distribution of the intravaginally administered progesterone dose through a first uterine pass effect. PMID- 20307897 TI - Carriage of diarrhoeagenic Escherichia coli by older children and adults in Accra, Ghana. AB - Diarrhoeagenic Escherichia coli (DEC) were sought in stool specimens from 72 adults and children aged over 3 years, who presented with diarrhoea at a hospital in Accra, Ghana, and 72 matched controls. Only diffusely-adherent E. coli were significantly associated with disease in these older individuals (P=0.029). We additionally tested 53 specimens from infants among whom DEC were collectively associated with disease (P=0.012). Enteropathogenic, enterotoxigenic and enteroaggregative E. coli, the most commonly isolated pathotypes from infants with diarrhoea, were frequently recovered from healthy adults. Asymptomatic carriage of DEC by older individuals in Accra may place young children at risk for diarrhoea. PMID- 20307898 TI - NADPH-d cells (mast cells) around and within the autonomic nerves of porcine renal hilus. AB - The enzymehistochemical localization of nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d) reactive cells next and within the autonomic nerves in the porcine kidney's hilus, close to renal artery and vein as well as in its adventitia, was studied. It was established that the prevailing part of NADPH-d-reactive cells were distributed next to and within NADPH-d-reactive autonomic fibers around the renal vein. Comparatively small number of reactive cells was found around the renal artery, but single NADPH-d-reactive cells were found in the neighbouring autonomic nerves as well. The cells observed next to nerves had much more expressed reaction (granules) than those, located in the nerves. Toluidine blue staining on frozen and paraffine sections from the same areas showed well-expressed gamma-ma metachromasia in mast cells with similar or identical localization. This indicated that observed reactive cells were mast cells. The obtained data convincingly showed that porcine NADPH-d cells may produce nitric oxide and in this way most probably they were involved in the function of autonomic nerves in the renal blood vessels (vasodilatation) and the kidney function, as well. PMID- 20307899 TI - Sorting of influenza A virus RNA genome segments after nuclear export. AB - The genome of the influenza A virus consists of eight different segments. These eight segments are thought to be sorted selectively in infected cells. However, the cellular compartment where segments are sorted is not known. We examined using temperature sensitive (ts) mutant viruses and cell fusion where segments are sorted in infected cells. Different cells were infected with different ts mutant viruses, and these cells were fused. In fused cells, genome segments are mixed only in the cytoplasm, because M1 prevents their re-import into the nucleus. We made a marker ts53 virus, which has silent mutations in given segments and determined the reassortment frequency on all segments using ts1 and marker ts53. In both co-infected and fused cells, all of marker ts53 segments and ts1 segments were incorporated into progeny virions in a random fashion. These results suggest that influenza virus genome segments are sorted after nuclear export. PMID- 20307900 TI - Electrochemical incineration of diclofenac in neutral aqueous medium by anodic oxidation using Pt and boron-doped diamond anodes. AB - The degradation of diclofenac, a common non-steroidal anti-inflammatory drug, in aqueous medium has been studied by anodic oxidation (AO) using an undivided cell with a Pt or boron-doped diamond (BDD) anode. Operating without pH regulation, AO with Pt acidifies the solution with precipitation of its protonated form, whereas using BDD, the solution becomes alkaline and only attains partial mineralization. Total incineration of low contents of the drug is feasible by AO with BDD in a neutral buffer medium of pH 6.5. Comparative treatment with Pt gives poor decontamination. The diclofenac decay always follows a pseudo first-order reaction. The increase in current for AO with BDD accelerates the degradative process, but decreases its efficiency. 2-Hydroxyphenylacetic acid, 2,5 dihydroxyphenylacetic acid, 2,6-dichloroaniline and 2,6-dichlorohydroquinone have been identified as aromatic intermediates. For AO with Pt, high amounts of malic, succinic, tartaric and oxalic acids are accumulated in the bulk and the N derivatives produced are rapidly destroyed with loss of NH4+. When BDD is employed, some carboxylic acids are also accumulated in small extent, with a larger persistence of oxalic and oxamic acids. The process involves the formation of different N-derivatives that slowly release NH4+ and NO3(-) ions. Chloride ion is lost in all cases. PMID- 20307901 TI - Association between reduced ADAMTS13 and diabetic nephropathy. AB - INTRODUCTION: Deficiency of Von Willebrand factor (VWF)-cleaving protease (ADAMTS13) causes platelet thrombosis in the microcirculation. Intrarenal coagulation is thought to be associated with the development and progression of diabetic nephropathy. Our aim was to clarify the association between plasma ADAMTS13 antigen (ADAMTS13Ag) levels and diabetic nephropathy. MATERIAL AND METHODS: We measured the plasma levels of VWF antigen (VWFAg) and ADAMTS13Ag, and calculated the VWF/ADAMTS13 ratio in 86 type 2 diabetic patients and 26 healthy volunteers, to investigate the relationship between these levels and renal function. With regard to diabetic macroangiopathy, the relationship between these levels and carotid intima-media thickness (IMT) was also investigated. RESULTS AND CONCLUSIONS: A significant positive and negative correlation was noted between ADAMTS13Ag and the estimated glomerular filtration rate (eGFR), vWF/ADAMTS13 ratio and eGFR, respectively. The diabetic patients were divided into normoalbuminuria (n=50), microalbuminuria (n=8) and overt nephropathy (n=28) groups. Compared among these three groups and the 26 healthy volunteers, ADAMTS13Ag was significantly lower only in the overt nephropathy group. The mean carotid IMT was measured in 69 patients and was significantly negatively correlated with ADAMTS13Ag and positively correlated with VWF/ADAMTS13 ratio. When these 69 patients were divided into four groups according to eGFR and ADAMTS13 levels (ADAMTS13/eGFR; low/low: n=12; high/low: n=7; low/high: n=25; high/high: n=25), the mean carotid IMT was increased in patients with a low ADAMTS13Ag in the same eGFR group. The present study suggests that reduced ADAMTS13 might be associated with diabetic nephropathy. PMID- 20307902 TI - Hepatocyte Growth Factor: a marker and a player in disseminated intravascular coagulation. PMID- 20307903 TI - Increases in circulating matrix metalloproteinase-9 levels following fibrinolysis for acute pulmonary embolism. AB - INTRODUCTION: Fibrinolyis is one of the first line therapies in high risk pulmonary embolism (PE) according to current guidelines. Previous studies showed that fibrinolytic therapy with tPA (tissue plasminogen activator, or alteplase) upregulates the concentrations of matrix metalloproteinases (MMPs) and contributes to hemorrhagic transformation after cardioembolic stroke. However, no previous study has described the circulating MMPs levels following fibrinolysis for acute PE. MATERIALS AND METHODS: We serially measured the circulating levels of MMPs (MMP-9 and MMP-2) and their endogenous inhibitors, the tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-2 in alteplase and in streptokinase treated patients with acute PE by gelatin zymography and by enzyme-linked immunosorbent assays, respectively. RESULTS: We found that therapy of PE streptokinase or with alteplase is associated increased pro-MMP-9, but not MMP-2, concentrations for up to 24hours, whereas no significant changes were found in TIMP-1 or TIMP-2 concentrations. This alteration returned to normal 3 to 5days after thrombolysis. This is the first study reporting on MMPs alterations following fibrinolysis for acute PE. CONCLUSIONS: We found transient increases in circulating pro-MMP-9 levels following fibrinolysis for acute PE. Our findings support the hypothesis that increased MMP-9 levels may underlie the risk of intracerebral hemorrhage or other bleeding complication of thrombolysis for acute PE, and the use of MMP inhibitors may decrease such risk. PMID- 20307904 TI - Do u txt? Event-related potentials to semantic anomalies in standard and texted English. AB - Texted English is a hybrid, technology-based language derived from standard English modified to facilitate ease of communication via instant and text messaging. We compared semantic processing of texted and standard English sentences by recording event-related potentials in a classic semantic incongruity paradigm designed to elicit an N400 effect. In participants fluent in both text and standard English, an N400 effect was elicited in both the texted and standard English conditions. The amplitude and distribution of the N400 effect (300-500ms) in the texted and standard English conditions were similar, but the text semantic incongruity effect was characterized by a delayed peak latency and an extended duration into the 500-700ms epoch. This pattern of results replicates previous findings regarding differences in the N400 effect in native and non-native language processing, but for the first time extends the bilingual ERP literature to include the technological phenomenon of texted English. PMID- 20307905 TI - Brief report: multilevel analysis of school smoking policy and pupil smoking behaviour in Wales. AB - A multilevel analysis of cross-sectional data from a survey involving 1941 pupils (in grades 10 and 11) and policy indicators developed from interviews with staff from 45 secondary schools in Wales examined the hypotheses that pupil smoking prevalence would be associated with: restrictive staff and pupil smoking policies; dissemination of school smoking policies; and implementation of smoking policies in the context of a health promoting whole school environment. The only statistically significant association found was that pupils attending schools that did not disseminate pupil smoking policy in a written document had a greater tendency (OR = 2.16, 95% CI 1.13-4.10) to smoke daily on school premises than those who attended schools that disseminated policy through a written document. This association was not significant (p < 0.05) when pupil level covariates were included. Further research is required to identify the effectiveness and optimal content, enforcement and support of school smoking policies. PMID- 20307907 TI - The impact of anti-HY responses on outcome in current and subsequent pregnancies of patients with recurrent pregnancy losses. AB - Women pregnant with a male fetus often generate cellular and humoral immune responses against male-specific minor histocompatibility (HY) antigens-however, the importance of these responses for pregnancy outcome is unclear. Epidemiologic studies have shown that the birth of a boy compared with a girl prior to a series of miscarriages significantly reduces the chance of a subsequent live birth and pregnancies with boys have an increased risk of placental abruption. This paper aims to review the current knowledge about the impact of anti-HY immunity on pregnancy outcome in terms of miscarriage and placental abruption. Our knowledge primarily comes from studies of the impact on pregnancy outcome of HLA class II alleles known to restrict CD4 T cell mediated anti-HY responses among 358 secondary recurrent miscarriage (SRM) patients and 203 of their children born prior to the miscarriages and investigation of these HLA alleles in 8 patients with recurrent severe placental abruptions. The chance of a subsequent live birth in SRM patients with firstborn boys compared to firstborn girls was significantly lower in women with HY-restricting HLA class II alleles [OR: 0.17 (0.1-0.4), p=0.0001]. Most patients with recurrent placental abruptions had firstborn boys and significantly more of these patients carried HLA haplotypes with HY restricting class II alleles compared with controls (p=0.009). These findings are strongly indicative of aberrant maternal immune reactions against fetal HY antigens playing a role in recurrent miscarriage and placental abruption. We propose pathogenetic pathways for these conditions that in our view best explain the findings. PMID- 20307906 TI - Bipolar disorder with frequent mood episodes in the New Zealand Mental Health Survey. AB - BACKGROUND: Rapid cycling bipolar disorder has been studied almost exclusively in clinical samples. METHODS: A national cross-sectional survey in 2003-2004 in New Zealand used the Composite International Diagnostic Interview (CIDI 3.0). Diagnosis was by DSM-IV. Depression severity was assessed with the Quick Inventory of Depressive Symptoms (QIDS) and role impairment using Sheehan Scales. Complex survey analyses compared percentages and means, and used logistic regression and discrete-time survival analyses. Frequent mood episodes (FMEs) in the past 12 months (4+) were used as an indicator of rapid cycling. RESULTS: The lifetime prevalence of bipolar disorder (I + II) was 1.7%. Twelve-month prevalence was 1.0%: 0.3% with FME and 0.7% with No FME (1-3 episodes). Another 0.7% had no episodes in that period. Age of onset was earliest for FME (16.0 years versus 19.5 and 20.1, p<.05). In the past 12 months, weeks in episode, total days out of role and role impairment in the worst month were all worse for the FME group (p<.0001) but both the FME and No-FME groups experienced severe and impairing depression. Lifetime suicidal behaviours and comorbidity were high in all three bipolar groups but differed little between them. About three-quarters had ever received treatment but only half with twelve-month disorder made treatment contact. LIMITATIONS: Recall, not observation of episodes. CONCLUSIONS: Even in the community the burden of bipolar disorder is high. Frequent mood episodes in bipolar disorder are associated with still more disruption of life than less frequent episodes. Treatment is underutilized and could moderate the distress and impairment experienced. PMID- 20307908 TI - Comment on "Adenoidectomy for otitis media with effusion in 2-3-year-old children" by Margaretha L. Casselbrant et al. [Int. J. Pediat. Otorhinolaryngol. 73 (2009) 1718-1724]. PMID- 20307909 TI - A prospective matched nested case-control study of bacterial gill disease outbreaks in Ontario, Canada government salmonid hatcheries. AB - Early-rearing salmonids in Ontario, Canada government fish hatcheries have been persistently affected by bacterial gill disease (BGD), and outbreaks at these locations have often been associated with high morbidity and mortality. The causative agent of BGD, Flavobacterium branchiophilum, is ubiquitous in fresh water, and outbreaks of BGD are considered to be associated with deleterious environmental conditions. This paper summarizes a 14-month rearing unit-level prospective nested matched case-control investigation at six Ontario government hatcheries (raising a total of six different salmonid species) to identify, and quantify the effects of, important predictors of BGD outbreaks. Ongoing husbandry data were collected on all early-rearing (<9 months of age) fish tank-lots ("tank lot"=a group of fish from a specific lot existing in a single hatchery tank for a given period during the study time frame) at participating hatcheries, and all outbreaks of BGD were confirmed by light microscopy during the study period. Control tank-lots were selected at the end of the study and matched to individual cases based on time, hatchery, and species. Data were analyzed using logistic regression modeling, controlling for fish age. The final multivariable model indicated that affected tank-lots were significantly more likely to have had lower fish numbers, lower individual fish weights, higher mortality levels and higher feeding rates during the week preceding observed BGD outbreaks than were asymptomatic control tank-lots. Refinements in the observation and manipulation of these factors could therefore aid in the prevention of fish losses associated with observable BGD outbreaks. The predictive (as opposed to causal) nature of the identified factors needs to be considered, and further research is required to understand the relationships between these factors and BGD. PMID- 20307910 TI - Predictors of acute bowel toxicity in patients treated with IMRT whole pelvis irradiation after prostatectomy. AB - PURPOSE/OBJECTIVE: Whole pelvis irradiation with IMRT (WPRT-IMRT) after prostatectomy is efficient in reducing acute toxicity: however, a number of patients still experience moderate acute bowel toxicity. MATERIALS AND METHODS: Ninety-six patients treated with WPRT-IMRT after prostatectomy with adjuvant or salvage intent were analysed. A number of parameters were individually recovered, including the DVHs of the intestinal cavity outside PTV and of the loops referred to both the WPRT phase and the whole treatment. Correlation between clinical dosimetric parameters and acute bowel toxicity was investigated by logistic analyses. Best predictive cut-off values for continuous variables were assessed by ROC curves. RESULTS: 15/96 (15.6%) Patients experienced grade 2 toxicity (no grade 3). Best dose-volume predictors were the fraction of loops receiving more than 45, 50 and 55 Gy (respectively, V45TL >= 50cc, V50TL >= 13cc, V55TL >= 3cc; p-values ranging from 0.005 to 0.027). Age, GU acute toxicity, rectal acute toxicity and time between prostatectomy and IMRT were also predictors of acute bowel toxicity. Multivariate analysis showed that the most predictive independent parameters were age (OR: 1.13; 95%CI: 1.02-1.25; p=0.021) and V50TL (>= 13cc, OR: 8.2; 95%CI: 1.7-40; p=0.009). CONCLUSIONS: The risk of moderate acute uGI toxicity during WPRT-IMRT for post-operatively treated patients increases with age; the risk is substantially reduced in patients with small overlap between PTV and loops. PMID- 20307911 TI - Trends in technology, trade and consumption likely to impact on microbial food safety. AB - Current and potential future trends in technology, consumption and trade of food that may impact on food-borne disease are analysed and the key driving factors identified focusing on the European Union and, to a lesser extent, accounting for the United States and global issues. Understanding of factors is developed using system-based methods and their impact is discussed in relation to current events and predictions of future trends. These factors come from a wide range of spheres relevant to food and include political, economic, social, technological, regulatory and environmental drivers. The degree of certainty in assessing the impact of important driving factors is considered in relation to food-borne disease. The most important factors driving an increase in the burden of food borne disease in the next few decades were found to be the anticipated doubling of the global demand for food and of the international trade in food next to a significantly increased consumption of certain high-value food commodities such as meat and poultry and fresh produce. A less important factor potentially increasing the food-borne disease burden would be the increased demand for convenience foods. Factors that may contribute to a reduction in the food-borne disease burden were identified as the ability of governments around the world to take effective regulatory measures as well as the development and use of new food safety technologies and detection methods. The most important factor in reducing the burden of food-borne disease was identified as our ability to first detect and investigate a food safety issue and then to develop effective control measures. Given the global scale of impact on food safety that current and potentially future trends have, either by potentially increasing or decreasing the food-borne disease burden, it is concluded that a key role is fulfilled by intergovernmental organisations and by international standard setting bodies in coordinating the establishment and rolling-out of effective measures that, on balance, help ensure long-term consumer protection and fair international trade. PMID- 20307912 TI - Pharmaceutical supply chain in China: current issues and implications for health system reform. AB - OBJECTIVE: This article discusses the performance and distortions of pharmaceutical market in China and provides some reflections and policy implications for currently implemented reform. METHODS: This study is based on literature review and publicly available data by searching electronic databases and official web pages of the Chinese government on the internet. RESULTS: China's economic transition and the incremental and piecemeal nature of health care reform have created a pharmaceutical market with a number of deficiencies, including ineffective supervision, mark-up price pattern, distortion of the price schedule, and lack of authoritative drug formulary. CONCLUSIONS: We conclude that the root cause of the market and government failures is that higher-than-cost drugs preferred by all suppliers. New drug pricing mechanism is the key to the current pharmaceutical reform and should be implemented in coordination with other health system reforms. PMID- 20307913 TI - Diagnosis of synchronous primary lung adenocarcinomas based on epidermal growth factor (EGFR) gene status: A case report. AB - The diagnosis of multiple primary lung cancer is sometimes difficult when multiple lung tumors with the same histologic type are identified. We now present a case of synchronous double primary lung adenocarcinomas (one in the right upper lobe and another in the right middle lobe) diagnosed based on mutational analysis of the epidermal growth factor receptor (EGFR) gene, although clinico pathological findings suggested the diagnosis of intrapulmonary metastasis. After complete resection, pathological sections revealed the similar pathological features of two adenocarcinomas and unexpected subcarinal nodal metastasis. As the L858R mutation within exon 21 of the EGFR gene was identified in the middle lobe tumor and the subcarinal node but not in the upper-lobe tumor, we diagnosed as double primary cancers. Local mediastinal recurrence after operation has been well-controlled with administration of gefitinib, a EGFR-tyrosine kinase inhibitor, and mutational analysis of the EGFR gene provided important information not only in the diagnosis of double primary cancers but also in decision-making of selection of chemotherapeutic agent. PMID- 20307914 TI - Transgenic apple expressing an antigenic protein of the human respiratory syncytial virus. AB - A gene coding for the human respiratory syncytial virus (RSV)-F protein, driven by the constitutively expressed CaMV 35S promoter, was introduced into leaf tissues of apple, Malusxdomestica Borkh. cv. Royal Gala, via Agrobacterium mediated transformation. Two putative transgenic lines were identified, and the presence of the RSV-F gene was confirmed by polymerase chain reaction (PCR). A total of 25 plants from these different transgenic events were successfully rooted, acclimatized, and transferred to the greenhouse. Stable integration of the transgene was confirmed and transgene copy number was determined by DNA gel blot analysis. Expression of the npt-II selectable marker and RSV-F was determined using reverse-transcription polymerase chain reaction (RT-PCR). Furthermore, enzyme-linked immunosorbent assay (ELISA) revealed varying levels of protein expression of the RSV-F transgene, ranging from 0 to 20 microg/g tissue. This is a first step in an effort to assess the efficacy of using apple for developing a plant-based vaccine against RSV. PMID- 20307915 TI - Costs of QuantiFERON-TB Gold versus tuberculin skin test in Spanish healthcare workers. AB - We compared the cost of the tuberculin skin test (TST) with the QuantiFERON-TB Gold (QFT-G) test when screening for latent tuberculosis in 134 healthcare workers in Spain. The QFT-G test cost euro42.5 per healthcare worker, while the TST cost euro39.5. The tests varied in cost structure; most (70%) TST costs were due to time demands on the participants, whereas the QFT-G was more expensive in terms of consumables (50% of the total cost). Accordingly, the results depend on the hourly wages of the participants and the time they must dedicate to the tests. In the Spanish healthcare system, the societal costs of QFT-G are comparable to those of the TST, although their cost structures are quite distinct. PMID- 20307916 TI - [Factors associated with hospital readmissions in the elderly]. AB - OBJECTIVE: To identify factors associated with hospital readmissions in the elderly. DESIGN: Observational descriptive study. SETTING: Health area 3 of Madrid. PARTICIPANTS: Patients 74 years-old and over with a hospital admission to Hospital Universitario Principe de Asturias in 2006. Those with a hospital admission in the previous 6 months were excluded. A total of 1051 patients were identified. MAIN MEASURES: Hospital Discharge Minimum Basic Data Set and primary care information system were used to develop logistical regression models. The dependent variable was the hospital readmission in a 6 month period. Independent variables were socio-demographics, health status and health care activity. RESULTS: There were 22.6% readmissions in the first 6 months. Variables associated with higher risk of readmission were, hospital stay (hospital stay greater than 15 days had an OR: 1.73 (95% CI:1.17-2.54), the total number of medicines prescribed to the patient (OR: 1.05; 95% CI:1.01-1.09), having hypertension (OR:1.56; 95% CI:1.11-2.18), heart failure (OR: 1.56; 95% CI:1.00 2.44) or ischemic heart disease (OR: 1.51; 95% CI:1.00-2.26), and the primary care nursing mean attendance pressure (OR: 0.93; 95% CI:0.87-0.98). The model that integrates information from both systems explains a higher number of factors associated with readmission. CONCLUSIONS: Hospital readmissions have been associated to patient medical condition and to factors related to the health care received. Integrating information from hospital and primary care administrative data bases improves the capacity to identify factors associated with a higher readmission risk. PMID- 20307917 TI - [Influenza A, what do our patients think about it?]. PMID- 20307918 TI - [Descending thoracic and abdominal aortic aneurysm in perfusion ventilation scintigraphy. An incidental finding]. PMID- 20307919 TI - New 6-amino-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazines and [1,2,4]triazolo[3,4-b] [1,3,4]thiadiazin-6-ones: synthesis, characterization and antibacterial activity evaluation. AB - (4-X-Phenylsulfonyl)phenyl] containing 6-amino-[1,2,4]triazolo[3,4 b][1,3,4]thiadiazines and [1,2,4]triazolo[3,4-b][1,3,4]thiadiazin-6-ones were synthesized by intermolecular condensation of 2-chloro-N-phenylacetamide, 2 chloroacetic acid, oxalylchloride and bromo-diethylmalonate with 4-amino-5-[4-(4 X-phenylsulfonyl)phenyl]-4H-1,2,4-triazole-3-thiols (X = H, Cl, Br). The structures of newly synthesized compounds were confirmed by elemental analysis and IR, NMR spectral data. All the compounds were screened for their antibacterial activities. Some of them exhibited good activities against Staphylococcus epidermidis ATCC 14990, Pseudomonas aeruginosa ATCC 9027, Staphylococcus aureus ATCC 25923 and Escherichia coli ATCC 25922. PMID- 20307920 TI - Application of in-situ measurement to determine 137Cs in the Swiss Alps. AB - Establishment of (137)Cs inventories is often used to gain information on soil stability. The latter is crucial in mountain systems, where ecosystem stability is tightly connected to soil stability. In-situ measurements of (137)Cs in steep alpine environments are scarce. Most studies have been carried out in arable lands and with Germanium (Ge) detectors. Sodium Iodide (NaI) detector system is an inexpensive and easy to handle field instrument, but its validity on steep alpine environments has not been tested yet. In this study, a comparison of laboratory measurements with GeLi detector and in-situ measurements with NaI detector of (137)Cs gamma soil radiation has been done in an alpine catchment with high (137)Cs concentration (Urseren Valley, Switzerland). The aim of this study was to calibrate the in-situ NaI detector system for application on steep alpine slopes. Replicate samples from an altitudinal transect through the Urseren Valley, measured in the laboratory with a GeLi detector, showed a large variability in (137)Cs activities at a meter scale. This small-scale heterogeneity determined with the GeLi detector is smoothed out by uncollimated in-situ measurements with the NaI detector, which provides integrated estimates of (137)Cs within the field of view (3.1 m(2)) of each measurement. There was no dependency of (137)Cs on pH, clay content and carbon content, but a close relationship was determined between measured (137)Cs activities and soil moisture. Thus, in-situ data must be corrected for soil moisture. Close correlation (R(2) = 0.86, p < 0.0001) was found for (137)Cs activities (in Bq kg( 1)) estimated with in-situ (NaI detector) and laboratory (GeLi detector) methods. We thus concluded that the NaI detector system is a suitable tool for in-situ measurements in alpine environments. This paper describes the calibration of the NaI detector system for field application under elevated (137)Cs activities originating from Chernobyl fallout. PMID- 20307921 TI - Anthropogenic input of polycyclic aromatic hydrocarbons into five lakes in western China. AB - The temporal distribution of polycyclic aromatic hydrocarbons (PAHs) was examined in dated sediments from five lakes in Western China. The surficial concentrations of seven carcinogenic PAHs (BaA, Chyr, BbF, BkF, BaP, DBA and INP, hereafter denoted as PAH7) were highly site-specific. The SigmaPAH7 concentrations generally increased from the deep layers to surface sediments. The temporal trends of SigmaPAH7 concentrations were clearly different from those reported in developed countries. From 1950s to 1980s, which PAHs started to decrease in developed countries, is the right period that PAHs started to increase rapidly in Western China. The fluxes and mass inventories suggest that the PAH7 input over the past three decades was much more rapidly than it was before the 1980s. Source identification indicates that the PAHs were primarily from biomass burning and domestic coal combustion, and increasing vehicular and/or industrial coal combustion emission was also found. PMID- 20307922 TI - Spatial distribution of heavy metal concentrations in urban, suburban and agricultural soils in a Mediterranean city of Algeria. AB - As part of a larger program aiming at assessing transfer and effects of metals in food webs, this work studied the spatial distribution of Cd, Cr, Cu, Pb, and Zn in 101 sub-surface soils, systematically sampled (1 x 1 km regular grid) over a large area around Annaba, the fourth most-populated city of Algeria. Cd and Cr exhibited only one abnormally high value, with all other concentrations being close to pedogeological background. Some places in the centre of the city were polluted by Pb (up to 823 mg kg(-1)), probably due to aerial deposition from gasoline exhausts. Zn never exceeded regulatory limits over the whole sampling area. Cu was the only element for which a spatial autocorrelation occurred. A spatial interpolation by cokriging allowed the identification of agricultural activities as the main Cu pollution source. Our approach revealed various anthropogenic pollution sources, more efficiently for large-scale patterns than for local abnormalities. PMID- 20307923 TI - The knowledge, education and behaviour of young people with regard to Chlamydia trachomatis in Aarhus, Denmark and Bonn, Germany: do prevention concepts matter? AB - Young people are at high risk of sexually transmitted infections, especially Chlamydia trachomatis, the most prevalent bacterial sexually transmitted disease in the developed world. Young people lack knowledge about sexually transmitted diseases (STDs) and are more aware of the risks of unwanted pregnancy than their risk of acquiring a STD. Different STD prevention concepts in different countries focus on different STDs. Based on explorative data analysis (Categorical Principal Component Analysis, CatPCA) this study, conducted in 2005, investigates the associations between self-estimation of sexual knowledge, active knowledge of chlamydia and HIV/AIDS, differing sex education and the sexual behaviour of 15-19 year old pupils from Aarhus, Denmark (N = 97), and Bonn, Germany (N = 93). A constructed knowledge, education and behaviour space model shows interesting associations between active STD knowledge and the sex education provided by both media and professionals. Sexual behaviour depends especially on sex education acquired through TV, Internet and print media. The young people from Aarhus and Bonn have significantly differing knowledge levels of chlamydia and HIV/AIDS. This is understood to be an effect of the different STD prevention concepts in Denmark and Germany. PMID- 20307924 TI - Differential effect of myocardial matrix and integrins on cardiac differentiation of human mesenchymal stem cells. AB - Dysregulation of matrix synthesis during myocardial fibrosis in post-infarct ventricular remodeling contributes to ventricular dysfunction. Bone marrow stem cell transplantation prevents functional deterioration following myocardial infarction. However, effect of myocardial extracellular matrix (ECM) on stem cell differentiation is poorly understood. We investigate the role of collagen matrices and integrin system in cardiac differentiation and engraftment of stem cells in infarcted myocardium. Sternum-derived bone marrow mesenchymal stem cells (MSCs) were differentiated into cardiomyocyte-like cells (CLCs). They were characterized using RT-PCR, immunofluorescence, flow cytometry and functional integrin neutralization assays. CLCs were injected into peri-infarct borders of injured myocardium of Wistar rats one week following left anterior descending (LAD) artery ligation. Cardiac function was analyzed via pressure-volume relationships. Cardiac differentiated CLCs displayed collagen V specificity, which was absent in undifferentiated MSCs. Collagen V, but not collagen I matrix, promoted attachment, proliferation and cardiac differentiation of CLCs. In contrast to beta(1), alpha(v) integrin contributed minimally in the attachment of CLCs on collagen matrices. However, inhibition of alpha(v)beta(3,) but not alpha(2)beta(1) integrin, selectively attenuated troponin T, sarcomeric alpha actin and ryanodine 2 receptor gene expression in CLCs. Both MSC and CLC transplantation prevented chamber dilatation and improved contractile function. However, systolic activity in MSC transplanted animals was accompanied by heightened wall stress as demonstrated by elevated myocardial end-diastolic pressure and prolonged tissue relaxation time. Localization of CLCs in the vicinity of collagen V-expressing myofibers promoted their integration into cardiac syncytium. CLCs may facilitate hemodynamic recovery by preserving tissue elasticity in the peri-infarct borders that sustains contractile efficiency for functional recovery in an actively remodeling infarcted myocardium. PMID- 20307927 TI - Genetic heterogeneity of inflammatory response and skin tumorigenesis in phenotypically selected mouse lines. AB - Non-inbred AIR (AIRmax, AIRmin) and Car (Car-S, Car-R) mouse lines were generated from the same eight inbred mice through bidirectional selective breeding for acute inflammatory response and for susceptibility to two-stage skin tumorigenesis, respectively. Because AIR lines also showed a differential predisposition to skin tumorigenesis and Car lines differed in the extent of inflammatory response, we carried out genome-wide association studies using SNP arrays to identify the genetic elements affecting skin tumor susceptibility and inflammatory response in AIR and Car lines. We found that the phenotypic outcome reflects a specific genetic profile in each mouse line, suggesting that distinct genetic elements, selected by differential genetic drifts, and exerting pleiotropic effects in each mouse population, control the skin tumor susceptibility and inflammatory response phenotypes. These findings point to the complex link between skin tumor susceptibility and inflammatory response in mice. PMID- 20307928 TI - PM, carbon, and PAH emissions from a diesel generator fuelled with soy-biodiesel blends. AB - Biodiesels have received increasing attention as alternative fuels for diesel engines and generators. This study investigates the emissions of particulate matter (PM), total carbon (TC), e.g., organic/elemental carbons, and polycyclic aromatic hydrocarbons (PAHs) from a diesel generator fuelled with soy-biodiesel blends. Among the tested diesel blends (B0, B10 (10 vol% soy-biodiesel), B20, and B50), B20 exhibited the lowest PM emission concentration despite the loads (except the 5 kW case), whereas B10 displayed lower PM emission factors when operating at 0 and 10 kW than the other fuel blends. The emission concentrations or factors of EC, OC, and TC were the lowest when B10 or B20 was used regardless of the loading. Under all tested loads, the average concentrations of total-PAHs emitted from the generator using the B10 and B20 were lower (by 38% and 28%, respectively) than those using pure petroleum diesel fuel (B0), while the emission factors of total-PAHs decreased with an increasing ratio of biodiesel to premium diesel. With an increasing loading, although the brake specific fuel consumption decreased, the energy efficiency increased despite the bio/petroleum diesel ratio. Therefore, soy-biodiesel is promising for use as an alternative fuel for diesel generators to increase energy efficiency and reduce the PM, carbon, and PAH emissions. PMID- 20307929 TI - Simultaneous metal leaching and sludge digestion by thermophilic microorganisms: effect of solids content. AB - High concentrations of heavy metal in livestock manures limit land application of their sludges. A practical and economical method of sludge treatment is important for converting the livestock sludge into soil conditioners or fertilizers. In this study, the effect of solid contents on the simultaneous aerobic digestion and metal leaching at thermophilic condition were investigated in a batch reactor. Different solid contents in the range of 0.5-4% (dry-w/v) were studied. The results showed that an increase of solid content decreased the pH reducing rate. It was the result of increase in buffering capacity and possible microbial inhibition at a higher solid content. Similar results were also found in the variations of ORP and sulfate concentrations during this process. In most cases, this biological process is able to solubilize 82-99% of heavy metals from the livestock sludge. It was found that the efficiency and rate of metal solubilization decreased with increasing solid contents. In addition, 54-80% of organic matter in the sludge was degraded after 28 days of reaction. A low sludge digestion efficiency was found at a high solid content. Moreover, the dewaterability of sludge was improved and the fertility (N, P and K) of sludge did not change significantly after this bioprocess. PMID- 20307930 TI - The use of artificial neural network (ANN) for modeling of COD removal from antibiotic aqueous solution by the Fenton process. AB - The study examined the implementation of artificial neural network (ANN) for the prediction and simulation of antibiotic degradation in aqueous solution by the Fenton process. A three-layer backpropagation neural network was optimized to predict and simulate the degradation of amoxicillin, ampicillin and cloxacillin in aqueous solution in terms of COD removal. The configuration of the backpropagation neural network giving the smallest mean square error (MSE) was three-layer ANN with tangent sigmoid transfer function (tansig) at hidden layer with 14 neurons, linear transfer function (purelin) at output layer and Levenberg Marquardt backpropagation training algorithm (LMA). ANN predicted results are very close to the experimental results with correlation coefficient (R(2)) of 0.997 and MSE 0.000376. The sensitivity analysis showed that all studied variables (reaction time, H(2)O(2)/COD molar ratio, H(2)O(2)/Fe(2+) molar ratio, pH and antibiotics concentration) have strong effect on antibiotic degradation in terms of COD removal. In addition, H(2)O(2)/Fe(2+) molar ratio is the most influential parameter with relative importance of 25.8%. The results showed that neural network modeling could effectively predict and simulate the behavior of the Fenton process. PMID- 20307931 TI - Biosorption of Zn(II) by live and dead cells of Streptomyces ciscaucasicus strain CCNWHX 72-14. AB - The biosorption characteristics of Zn(II) using live and dead cells of Streptomyces ciscaucasicus strain CCNWHX 72-14 as biosorbents have been investigated in the present research. Optimum conditions for biosorption were determined to be: pH adjusted to 5.0, agitated at 90 rpm and at a dose of 2 g/L. For initial zinc concentrations of 1-150 mg/L, batch biosorption data of live biomass preferred to be simulated with Freundlich model while those of dead strain fit Langmuir isotherm well. Experimental maximum biosorption capacity turned out to be 42.75 mg/g (0.654 mmol/g) for living material and 54 mg/g (0.826 mmol/g) for dead sorbents, respectively. The pseudo-second-order equation, instead of the pseudo-first-order one, was chosen to describe the time course biosorption process. In contrast to live biosorbents, dead biomass seemed to have lower binding strength with higher desorption efficiency at pH 1.0. Competitive biosorption revealed the order of competing metal ion to be: Cu(2+)>Cd(2+)>Ni(+). FT-IR analysis indicated that more functional groups were involved in the biosorption process of dead adsorbents, compared with those linked to live biomass. Taken together, it can be concluded that dead cells of CCNWHX 72-14 were better and cheaper biosorbents than live ones. PMID- 20307932 TI - Adsorption of Cr(VI) using Fe-crosslinked chitosan complex (Ch-Fe). AB - In the present investigation, Fe-chitosan crosslinked is used as adsorbent for the removal of chromium from aqueous solutions. The influence of pH, temperature and other ions was evaluated. pH 2.0 was found to be the optimum pH for adsorption of Cr(VI) onto Ch-Fe. Coordination of unsaturated sites for the iron(III) complex of polymer were considered to be the adsorption sites for Cr(VI) species, the predominant species being HCrO(4)(-). The Langmuir and Langmuir-Freundlich adsorption isotherm models were applied to describe the isotherm parameter for Cr(VI) adsorption. The results indicate that the Langmuir Freundlich adsorption model and maximum adsorption capacity was calculated as 295 mg/g at 25 degrees C, with pH 4.7. Cr(VI) uptake on the adsorbent decreased from 295 mg/g at 25 degrees C to 209 mg/g at 65 degrees C. Rate constants as a function of temperature were evaluated with the help of a proposed second order kinetic model. The other coexisting ions, nitrate, chlorides and sulphate influenced Cr(VI) adsorption. PMID- 20307933 TI - Reply to the topical review entitled "the phenomenon of changes in cortical excitability in migraine is not migraine-specific--a unifying thesis" by Anne Stankewitz and Arne May published in Pain 2009;145:14-7. PMID- 20307934 TI - Compensation claim lodgement and health outcome developmental trajectories following whiplash injury: A prospective study. AB - This study aimed to identify distinctive trajectories for pain/disability and posttraumatic stress disorder (PTSD) symptoms following whiplash injury and to examine the effect of injury compensation claim lodgement on the trajectories. In a prospective study, 155 individuals with whiplash were assessed at <1month, 3, 6 and 12months post injury. Outcomes at each time point were Neck Disability Index (NDI) and the Posttraumatic Stress Diagnostic Scale (PDS). Group-based trajectory analytical techniques were used to identify outcome profiles. The analyses were then repeated after including third party compensation claim lodgment as a binary time-changing covariate. Three distinct NDI trajectories were determined: (1) Mild: mild or negligible pain/disability for the entire 12 months (45%), (2) Moderate: initial moderate pain/disability that decreased to mild levels by 3 months (39%) and (3) Chronic-severe: severe pain/disability persisting at moderate/severe levels for 12 months (16%). Three distinct PTSD trajectories were also identified: (1) Resilient: mild symptoms throughout (40%), (2) Recovering: initial moderate symptoms declining to mild levels by 3months (43%) and (3) Chronic moderate-severe: persistent moderate/severe symptoms throughout 12 months (17%). Claim submission had a detrimental effect on all trajectories (p<0.001) except for the Chronic-severe NDI trajectory (p=0.098). Following whiplash injury, there are distinct pathways of recovery for pain/ disability and PTSD symptoms. Management of whiplash should consider the detrimental association of compensation claim with psychological recovery and recovery of those with mild to moderate pain/disability levels. However, claim lodgement has no significant association with a more severe pain and disability trajectory. PMID- 20307935 TI - Efficacy of pyrantel pamoate and ivermectin paste formulations against naturally acquired Oxyuris equi infections in horses. AB - In recent years, numerous veterinary practitioners have reported anecdotal episodes in which anthelmintic treatment did not appear to deliver the expected efficacy against equine pinworms (Oxyuris equi). Anthelmintic resistance has not been demonstrated formally in equine pinworms, so a clinical study was designed to evaluate the efficacy of paste formulations of pyrantel pamoate or ivermectin against naturally acquired infections with O. equi. Twenty-one horses (>4 months to 15 years of age) with patent, naturally acquired pinworm infections were blocked by source of origin and allocated randomly to one of three treatment groups: horses (n=7) assigned to Group 1 were treated orally with pyrantel pamoate paste at a dosage of 13.2 mg/kg (2x label dosage), Group 2 horses (n=7) were untreated controls, and horses (n=7) assigned to Group 3 were treated orally with ivermectin paste at a dosage of 200 microg/kg. Fourteen days after treatment, horses were euthanatized, necropsied, and large intestinal contents were processed for recovery of adult pinworms. In addition, duplicate 1% aliquots of intestinal contents from the cecum, ventral colon, dorsal colon, and small colon were collected, preserved, and examined for recovery and enumeration of fourth-stage larval O. equi. Anthelmintic efficacy against pinworms was evaluated by comparing the post-treatment worm counts of Groups 1 and 3 to those of control animals. Mean numbers of O. equi adults recovered postmortem were significantly decreased by both pyrantel pamoate (P=0.0366) and ivermectin (P=0.0137) treatment, with respective efficacies of 91.2% and 96.0%. In addition, both products demonstrated >99% efficacy against fourth-stage O. equi larvae. The current study demonstrated acceptable adulticidal and larvicidal efficacy of both pyrantel pamoate and ivermectin paste formulations against O. equi and did not support the existence of macrocyclic lactone or pyrimidine resistance in the pinworm populations evaluated. PMID- 20307936 TI - Efficacy of pyrantel pamoate against a macrocyclic lactone-resistant isolate of Parascaris equorum in horses. AB - The expanding prevalence of Parascaris equorum populations that are resistant to macrocyclic lactone (ML) anthelmintics makes it desirable to identify dewormers which remain effective. The objective was to evaluate the efficacy of pyrantel pamoate in 14 suckling foals that had been infected orally with approximately 600 larvated eggs of a P. equorum isolate selected for ML resistance (ML-R). Seventy days after inoculation, foals were weaned, housed individually, and fecal samples were examined frequently to detect the onset of patency. Between 73 and 80 days post-inoculation, all 14 foals developed P. equorum egg counts>or=150 eggs per gram (EPG). An initial cohort of eight foals was treated orally with ivermectin paste (200 microg/kg) 84-91 days post-inoculation. Egg counts were reduced by only 47% at 2 weeks after ivermectin treatment, confirming the ML-R status of the isolate. A second cohort of six foals was not treated with ivermectin. Within each cohort, eligible foals were allocated randomly to treated (pyrantel pamoate; n=7) or untreated control (n=7) groups. Treated foals were dosed orally on Day 0 with a paste formulation of pyrantel pamoate at 13.2mg/kg. Mean ascarid egg counts of treated foals were reduced by 96.0% and 98.8% at 1 and 2 weeks post treatment, respectively. On Day 14, foals were euthanatized and specimens of P. equorum were recovered from the gut contents, preserved in 10% formalin, and counted. Mean numbers of P. equorum adults recovered postmortem were significantly lower (P=0.0031) in foals treated with pyrantel pamoate (X=1.7; range 0-16) compared to control foals (X=63.0; range 0-320). A paste formulation of pyrantel pamoate, at a dosage of 13.2 mg/kg, was 97.3% effective against a ML R isolate of P. equorum. PMID- 20307937 TI - Meningomyelitis due to nematode infection in four cats. AB - Spinal cord parasitic migrations in cats are uncommon. This report describes four cases of chronic hindlimb paraparesis in cats associated with nematode infection. Complete neurologic, hematologic, serum chemistry and radiographic examination was performed on all animals. Computed tomographic (CT)-myelographic examination at the lumbar area in one cat showed a slight swelling of the spinal cord. Necropsy examination of the spinal cord revealed generalized edema and marked submeningeal hemorrhage at the thoracic region in three cats. On histopathologic examination, numerous sections of adult nematodes and eggs were present in histological sections of the affected spinal cord segments in all cats. The morphologic features of the nematode, location and appearance of the lesions suggest that the parasite responsible for the paralysis in these cats is Gurltia paralysans. PMID- 20307938 TI - Biodiversity and distribution of helminths and protozoa in naturally infected horses from the biosphere reserve La Sierra Madre de Chiapas", Mexico. AB - A cross sectional survey was performed to identify gastrointestinal helminths and protozoans in naturally infected horses from the biosphere reserve known as "La Sierra Madre de Chiapas", Mexico (El Triunfo and La Sepultura). During a three year survey, fecal samples from 90 horses and parasites from 2 necropsied animals were collected. Five families from the Nematoda class: Ascaridae, Kathlanidae, Oxyuridae, Strongylidae and Trichostrongylidae were found, whereas, only one family from the class Cestoda, was observed: Anoplocephalidae. One family from the class Insecta, was observed: Gasterophiilidae. The number of species of parasites ranged from 13 to 18 with an average of 15 per animal. Adult parasites were recovered from the large intestine luminal contents at necropsy. Species recovered included: Strongylus vulgaris, S. equinus, S. edentatus, Oxyuris equi, Parascaris equorum, Coronocyclus coronatum, C. labiatus, C. labratus, Cyathostomum tetracanthum, Cylicocyclus insigne, C. leptostomus, Cylicodontophorus bicoronatus, Cylicostephanus asymetricus, C. bidentatus, C. minutus, C. longibursatus, Petrovinema poculatum, Poteriostomum imparidentatum, Cylicostephanus goldi, Tridentoinfundibulum gobi, Triodontophorus serratus and T. tenuicollis. One species of Diptera were recovered from stomach and identified: Gasterophilus intestinalis. Furthermore, different species of protozoa were recovered from fresh horse-dung and identified in four classes: Sporozoa, Litostomatea, Ciliasida and Suctoria. Nine families: Cryptosporidiidae, Eimeriidae, Balantidiidae, Buetschliidae, Blepharocorythidae, Cycloposthiidae, Spirodiniididae, Ditoxidae, Acinetidae; and 31 ciliates species were recorded: Allantosoma dicorniger, A. intestinalis, Alloiozona trizona, Blepharosphaera intestinalis, Blepharoprosthium pireum, Blepharoconus benbrooki, Bundleia postciliata, Didesmis ovalis, D. quadrata, Sulcoarcus pellucidulus, Blepharocorys angusta, B. cardionucleata, B. curvigula, B. juvata, B. uncinata, B. valvata, Cycloposthium bipalmatum, C. edentatum, C. scutigerum, Charonina equi, Ditoxum funinucleum, Spirodinium equi, Tetratoxum unifasciculatum, Triadinium caudatum, T. galea, T. minimum and Tripalmaria dogieli. Other ciliate observed and recorded was Ochoterenaia appendiculata. This study describes the biodiversity and distribution of common and new helminths and protozoas found in the gastrointestinal tract from horses in the biosphere reserve "Sierra Madre de Chiapas" in Mexico. PMID- 20307939 TI - Binding of serum albumin to the anthelmintic drugs albendazole, triclabendazole and their sulphoxides. AB - The binding of drugs to plasma proteins--especially serum albumin--is an important factor in controlling the availability and distribution of these drugs. In this study we have investigated the binding of two drugs commonly used to treat liver fluke infections, albendazole (ABZ) and triclabendazole (TCBZ), and their sulphoxide metabolites to bovine serum albumin (BSA). Both ABZ and TCBZ caused shifts in the mobility of BSA in native gel electrophoresis. No such changes were observed with the sulphoxides under identical conditions. The drugs, and their sulphoxides, caused quenching of the intrinsic tryptophan fluorescence of BSA, indicating association between the drugs and this protein. Quantification of this quenching suggested a 5-10-fold reduction in affinity of the sulphoxides compared to the parent compounds. These results are discussed in respect to previous work on the pharmacodynamics of these fasciolicides and will inform the design of novel anthelmintics. PMID- 20307940 TI - State associations with the cortisol awakening response in healthy females. AB - The current study examined intra-individual relationships between the cortisol awakening response (CAR) and state sleep-related and psychosocial variables in a pooled design study. 12 healthy female participants (age range: 22-41 years.) were examined on 12 study days each, occurring at three-day intervals. Quantitative diaries capturing state sleep-related and psychosocial variables were filled out on the evening before each study day as well as 45 min post awakening on the study day. On each study day, salivary free cortisol was determined at 0, 15, 30, and 45 min post-awakening. Relationships between cortisol measures and psychosocial variables were analysed using dummy-variable linear regression models. State variability in the CAR (area under increase curve; AUC(I)) was found to be inversely related to simultaneous variability in awakening time (beta=-.29, p<.005) and positively related to variability in adverse psychosocial states of stress (beta=.22, p<.01) and tension (beta=.32, p<.001) measured 45 min post-awakening. In addition, levels of the CAR were also found to decrease linearly over the study period across participants (beta=-.19, p<.01) and this time trend could not be explained through a relationship between the CAR and any of the examined variables. The results are discussed within the context of previous evidence and potential implications for cross-sectional research are highlighted. PMID- 20307941 TI - Mucous cysts. PMID- 20307942 TI - Factors determining the impact of care-giving on caregivers of elderly patients with dementia. A systematic literature review. AB - INTRODUCTION: Dementia caregivers suffer a considerable care burden. More than in comparable groups of caregivers or peers, they are confronted with feelings of depression and decreased physical health. Although many studies are set up to determine the link between the stressors in dementia care-giving and the impact on the family caregiver, the results remained inconclusive. Others, depression in caregivers remains the main cause of a premature or acute ending of home care. METHOD: The aim of this systematic literature review was to analyse what factors determine the development of depression in caregivers of elderly patients with dementia. Depression was taken as primary outcome as it is shown to be the main reason for caregivers to abandon home care. RESULTS: Depression occurs in one in three of caregivers and it occurs more frequently in those who care for patients with dementia than in caregivers of patients with other chronic illnesses. CONCLUSION: Caregiver characteristics rather than objective care needs of the patients tend to be responsible for the onset of depression. Future research should concentrate on demonstrating links between negative feelings in caregivers and the way the care situation evolves. This can have important implications in home care support. PMID- 20307943 TI - Obesity in older mothers, gestational weight gain, and risk estimates for preterm phenotypes. AB - OBJECTIVE: To assess whether advanced maternal age modifies the relationship between maternal pregravid weight status, gestational weight gain patterns, and the occurrence of spontaneous preterm birth (SPB) and medically indicated preterm birth (MIPB). METHODS: Retrospective cohort analysis of vital statistics data from the state of Florida for the period 2004 through 2007 comprising 311,422 singleton pregnancies (two age groups: 20-24 years old or younger women and >or=35 years or older women). Mothers were classified into five clusters based on their pre-pregnancy body mass index (BMI) values: non-obese (less than 30), class I obese (30.0or=50.0). RESULTS: MIPB occurred more frequently among older than younger women [11.8% vs. 6.4%, respectively (p<0.0001)) whereas SPB occurred more frequently among younger women [11.3% vs. 10.5%, respectively (p<0.0001)). Maternal obesity increased the risk for MIPB but not for SPB. Regardless of BMI status, the risk of MIPB was elevated among older mothers, particularly among those with suboptimal (<0.23 kg/week) and supraoptimal (>0.68 kg/week) gestational weight gain. A dose-response relationship with increasing gestational weight gain was evident (p<0.01); the greatest risk for MIPB occurred among older mothers with weekly gestational weight gain in excess of 0.79 kg (OR=7.76, 95% CI=5.73-10.5). CONCLUSION: The occurrence of medically indicated preterm birth is positively associated with increased maternal pregravid body weight, older maternal age and extremes of gestational weight gain. Targeted pre- and inter-conception weight management efforts should be particularly encouraged in older mothers. PMID- 20307944 TI - 'Bipolar disorder' in the elderly: what's in a name? AB - Bipolar disorder is a chronic disorder of mood which leads to episodes of either elevated mood or depression in a sizable number of adults in the community (1%). Though the prevalence rates in the elderly are lower in the community (up to 0.1%), there is significantly higher morbidity in protected environments like care homes and hospital settings where prevalence rates may be as high as 10%. Bipolar disorder in the elderly is probably heterogenous and its etiopathogenesis is complex. Bipolar disorder may be divided into two distinct subtypes, the late onset bipolar (LOB) and the early onset bipolar (EOB) groups. LOB patients tend to have a milder illness in terms of manic severity but they have higher medical and neurological burden. They also have lower familial burden of bipolar illness as compared to EOB patients. There is an increased risk of dementia and stroke in patients with late life bipolar disorder (and there may be a protective effect of lithium in preventing dementia). White matter changes, as seen by increased white matter hyperintensities on neuroimaging, are also increased, providing further evidence of cerebrovascular disease. Treatment of late life bipolar is currently based on guidelines drawn up for younger bipolar disorder patients. Good quality intervention studies are needed to estimate the possible protective effect of cognitive enhancers and/or vascular prevention strategies. This review suggests that late life bipolar disorder, particularly late onset bipolar disorder, is probably a distinct diagnostic entity compared to the younger bipolar patients as it has a different presentation, etiology and hence perhaps needs different treatment strategies. PMID- 20307945 TI - Preventing and treating the accelerated ageing of obesity. AB - Advances in the molecular biology of ageing, insulin resistance, inflammation, carcinogenesis and caloric restriction have elucidated commonalities relevant to the chronic overnutrition syndrome termed obesity. Not until the expanded acceptance and availability of surgical treatment of obesity ("bariatric surgery") has it been possible to explore the beneficial effects of sustained voluntary weight loss through controlled undernutrition in freely living people. Bariatric surgery is 58 years old and has undergone dramatic improvements recently becoming significantly safer and more accessible owing to the development of minimally invasive approaches and other advances. Furthermore, it is cost-effective compared to all forms of non-operative treatment. Thus older candidates, with more numerous and severe comorbidities are being recruited, increasing the pool of patients who have had operations which extend the otherwise shorter lives of the obese. Here we describe two mechanistically different operations, gastric restrictive and diversionary, and address their risks, complications, side-effects and beneficial outcomes, in aggregate increasing longevity, reducing morbidity and most important: improving health related quality-adjusted life years. PMID- 20307946 TI - Menopause and myocardial infarction risk among employed women in relation to work and family psychosocial factors in Lithuania. AB - OBJECTIVES: To assess the relationship between menopause and age at menopause and the risk of the first non-fatal myocardial infarction taking into account the possible influence of psychosocial job characteristics, marital stress, level of social support, educational level, occupation, age and traditional ischemic heart disease risk factors. METHODS: Population-based case-control study among 35-61 years old employed women in Kaunas, Lithuania. Totally 122 myocardial infarction cases and 371 controls were interviewed in 2001-2004. The logistic regression analysis was performed. RESULTS: Younger age at menopause (0.05). CONCLUSION: Bilateral thalamic diffusion properties are altered in temporal lobe epilepsy. The presence of hippocampal sclerosis enhances the change ipsilaterally. PMID- 20307958 TI - Augmented renal clearance in the Intensive Care Unit: an illustrative case series. AB - The substantial underlying disease burden, in combination with the therapeutic interventions provided, can result in significantly altered end-organ function in the critically ill. These changes can in turn affect key pharmacokinetic (PK) indices for many antibiotics, including drug clearance, promoting potentially subtherapeutic concentrations for lengthy periods of the dosing interval, therapeutic failure or the selection of resistant organisms. This paper presents three instructional cases from our tertiary-level Intensive Care Unit, where established antibiotic dosing regimens failed to achieve predefined PK targets for optimal bacterial killing. Using therapeutic drug monitoring (TDM), significant dose modification was subsequently undertaken. We propose augmented renal clearance as a possible mechanism underlying this phenomenon, particularly in young post-operative, burns or head-injured patients with normal serum creatinine concentrations. TDM, or at least a measured creatinine clearance, should be considered early in this setting to allow the optimisation of antibiotic exposure. PMID- 20307959 TI - The physicochemical properties of a spray dried glutinous rice starch biopolymer. AB - Glutinous rice starch (GRS) is a biopolymer used widely in the food industry but not at all in the pharmaceutical industry. There are several ways to modify this biopolymer. Physical modification is simple and cheap because it requires no chemicals or biological agents. The aim of this study was to characterize the physicochemical properties of a spray dried glutinous rice starch (SGRS) produced from pregelatinized GRS. The surface morphology changed from an irregular to concave spherical shape as revealed by Scanning Electron Microscopy (SEM). SGRS was almost amorphous as determined by X-ray Diffraction (XRD) spectroscopy. The water molecules became linked through hydrogen bonds to the exposed hydroxyl group of amorphous SGRS as determined by Near Infrared (NIR) spectroscopy. Then, SGRS formed a colloid gel matrix with water and developed a highly viscous gelatinous form as determined using Differential Scanning Calorimetry (DSC) and a stress control type rheometer. In addition, SGRS can swell and produce a gelatinous surface barrier like a hydrophilic matrix biopolymer which controls drug release. Therefore, a novel application of SGRS is as a sustained release modifier for direct compression tablets in the pharmaceutical industry. PMID- 20307960 TI - Adsorption of albumin and sodium hyaluronate on UHMWPE: a QCM-D and AFM study. AB - The biotribological properties of artificial joints, in particular the efficiency of the lubrication, strongly determine their lifetime. The most commonly used artificial joints combine a metallic or ceramic part articulating against a ultra high molecular weight polyethylene (UHMWPE) counterface, and are lubricated by the periprosthetic fluid. This fluid contains several macromolecules, namely albumin and sodium hyaluronate (NaHA), that are known to be involved in the lubrication process. There are several studies in the literature concerning the interaction of the referred macromolecules with ceramic or metallic prosthetic materials. However, to our knowledge, information about their binding to the polymeric surface is practically inexistent. The objective of this work is to contribute to clarify the role played by albumin and NaHA on the biolubrication process, through the investigation of their interaction with the UHMWPE surface. The study involves adsorption measurements using a quartz crystal microbalance with dissipation (QCM-D), the characterization of the adsorbed films by atomic force microscopy (AFM) and wettability determinations. Albumin was found to adsorb strongly and extensively to the polymer, while NaHA led to a very low adsorption. In both cases rigid films were obtained, but with different morphology and porosity. The high binding affinity of the protein to the polymer was demonstrated both by the results of the fittings to Langmuir and Freundlich models and by the values of the adhesion forces determined by AFM. In the simultaneous adsorption of albumin and NaHA, protein adsorption is predominant and determines the surface properties. PMID- 20307961 TI - Selective adsorption of small proteins on large-pore anion exchangers coated with medium size proteins. AB - A new anion exchanger support has been designed for the selective adsorption of small proteins. This has been achieved activating an aminated support with glutaraldehyde and further coating the support surface with bovine serum albumin (BSA). In this support, "wells" are generated by two neighborhoods BSA molecules, on the bottom of those "wells" glutaraldehyde groups are exposed out ready to react with small molecules that have a size small enough to be accommodated between two BSA molecules on the pre-existing support. However, the BSA surface was not inert enough adsorbing many proteins, thereby reducing the selectivity of the system. A further solution was coating the immobilized BSA molecules with dextran, reducing the adsorption of protein on the BSA surface. This new matrix has been evaluated in the selective adsorption of the very small beta lactoglobulins and alpha-lactalbumin from dairy whey, achieving the selective adsorption of both small proteins while other larger proteins from dairy whey remained in the supernatant. Moreover, a protein crude extract has been offered to the new matrix, and only small proteins could be adsorbed on the support (as probed by gel filtration). Thus this amino-glutaraldehyde-BSA-dextran-Sepharose is a matrix that may be used to selectively ionically adsorb proteins that were smaller than BSA (62 kDa). This strategy may be used for any other kind of adsorbing groups (chelating agents, boronic acid, etc.), or using proteins with different sizes to coat the support, designing tailor-made supports that may permit the fractioning of proteins following their sizes and by adsorption/desorption on different matrices. PMID- 20307962 TI - Involvement of catalase in the protective effect of binaphthyl diselenide against renal damage induced by glycerol. AB - In the present study, the protective effect of binapthyl diselenide [(NapSe)(2)] was investigated on glycerol-induced renal damage in rats. Adult male Wistar rats were treated with (NapSe)(2) (50 mg/kg, orally) or vehicle. After 24 h (NapSe)(2) treatment, the animals received an intramuscular injection of glycerol (8 ml/kg, dissolved in saline) or vehicle as a divided dose into the hind limbs. Twenty four hours afterwards, rats were euthanized and the levels of urea and creatinine were measured in plasma. Non-protein thiol (NPSH) levels and catalase (CAT) activity were evaluated in renal homogenates. Histopathological evaluations were also performed in kidneys of rats. The rats exposed to glycerol presented swelling of the proximal and distal tubules with evidence of cell damage and death. Glycerol-exposed rats presented an increase in renal failure markers (plasmatic urea and creatinine levels) and a reduction in renal CAT activity. No change was observed in NPSH levels in kidneys of rats exposed to glycerol. (NapSe)(2) protected against the alterations caused by glycerol in rats. (NapSe)(2) increased per se NPSH levels (33%) in kidneys of rats. In conclusion, the results demonstrated that treatment with (NapSe)(2) protected against renal damage induced by glycerol in rats, probably due to its antioxidant effect. PMID- 20307963 TI - Functional relationship between cationic amino acid transporters and beta defensins: implications for dry skin diseases and the dry eye. AB - The ocular surface, constantly exposed to environmental pathogens, is particularly vulnerable to infection. Hence an advanced immune defence system is essential to protect the eye from microbial attack. Antimicrobial peptides, such as beta-defensins, are essential components of the innate immune system and are the first line of defence against invaders of the eye. High concentrations of L arginine and L-lysine are necessary for the expression of beta-defensins. These are supplied by epithelial cells in inflammatory processes. The limiting factor for initiation of beta-defensin production is the transport of L-arginine and L lysine into the cell. This transport is performed to 80% by only one transporter system in the human, the y(+)-transporter. This group of proteins exclusively transports the cationic amino acids L-arginine, L-lysine and L-ornithine and is also known under the term cationic amino acid transporter proteins (CAT proteins). Various infections associated with L-arginine deficiency (for example psoriasis, keratoconjuctivitis sicca) are also associated with an increase in beta-defensin production. For the first time, preliminary work has shown the expression of human CATs in ocular surface epithelia and tissues of the lacrimal apparatus indicating their relevance for diseases of the ocular surface. In this review, we summarize current knowledge on the human CATs that appear to be integrated in causal regulation cascades of beta-defensins, thereby offering novel concepts for therapeutic perspectives. PMID- 20307964 TI - Phytotoxicity of landfill leachate on willow--Salix amygdalina L. AB - Because of low investment and operational costs, interest is increasing in the use of willow plants in landfill leachate disposal. Toxic effects of leachate on the plants should be avoided in the initial period of growth and phytotoxicological testing may be helpful to select appropriate leachate dose rates. The aim of this study was to determine the phytotoxicity of landfill leachate on young willow (Salix amygdalina L.) cuttings, as a criterion for dose rate selection in the early phase of growth. Over a test period of 6 weeks plants were exposed to six concentrations of landfill leachate solutions (0%; 6.25%; 12.5%; 25%; 50% and 100%), under two different regimes. In regime A willow plants were cultivated in leachate solution from the beginning, whereas in regime B they were grown initially in clean water for 4 weeks, after which the water was exchanged for leachate solutions. The lowest effective concentration causing toxic effects (LOEC) was calculated (p<0.05). In regime A LOEC was between 5.44% and 6.50% of leachate concentration, but slightly higher in regime B (5.32 6.59%). Willow plants were able to survive in landfill leachate solutions with electrical conductivity (EC) values up to 5.0 mS/cm in regime A, whereas in regime B plants were killed when EC exceeded 3.0 mS/cm. This indicates an ability of willow plants to tolerate higher strengths of landfill leachate if they are cultivated in such concentrations from the beginning. PMID- 20307965 TI - Electrochemical detection of dopamine in the presence of ascorbic acid using graphene modified electrodes. AB - Dopamine plays a significant role in the function of human metabolism. It is important to develop sensitive sensor for the determination of dopamine without the interference by ascorbic acid. This paper reports the synthesis of graphene using a modified Hummer's method and its application for the electrochemical detection of dopamine. Electrochemical measurements were performed at glassy carbon electrode modified with graphene via drop-casting method. Cyclic voltammogram of ferri/ferrocyanide redox couple at graphene modified electrode showed an increased current intensity compared with glassy carbon electrode and graphite modified electrode. The decrease of charge transfer resistance was also analyzed by electrochemical impedance spectroscopy. The capacity of graphene modified electrode for selective detection of dopamine was confirmed in a sufficient amount of ascorbic acid (1 mM). The observed linear range for the determination of dopamine concentration was from 4 microM to 100 microM. The detection limit was estimated to be 2.64 microM. PMID- 20307967 TI - Auditory representations and memory in birdsong learning. AB - Songbirds are well suited to studies of vocal processing not only because of their impressive motor abilities, but also because of their exquisite sensory system that allows them to detect subtle song variability, memorize complex songs, and monitor auditory feedback during singing. Recent experiments point to areas outside the traditional song system for being relevant to sensory functions implicated in song learning. By manipulating or suppressing activity in these areas, adult birds lose their ability to recognize the songs of their tutors and juveniles are unable to form accurate copies of tutor song. Taken together, these experiments show that the sensory mechanisms for vocal learning encompass a larger network than previously thought. PMID- 20307966 TI - Dynamics of Active Sensing and perceptual selection. AB - Sensory processing is often regarded as a passive process in which biological receptors like photoreceptors and mechanoreceptors transduce physical energy into a neural code. Recent findings, however, suggest that: first, most sensory processing is active, and largely determined by motor/attentional sampling routines; second, owing to rhythmicity in the motor routine, as well as to its entrainment of ambient rhythms in sensory regions, sensory inflow tends to be rhythmic; third, attentional manipulation of rhythms in sensory pathways is instrumental to perceptual selection. These observations outline the essentials of an Active Sensing paradigm, and argue for increased emphasis on the study of sensory processes as specific to the dynamic motor/attentional context in which inputs are acquired. PMID- 20307969 TI - Targeting the transforming growth factor-beta signalling pathway in metastatic cancer. AB - Transforming growth factor (TGF)-beta signalling plays a dichotomous role in tumour progression, acting as a tumour suppressor early and as a pro-metastatic pathway in late-stages. There is accumulating evidence that advanced-stage tumours produce excessive levels of TGF-beta, which acts to promote tumour growth, invasion and colonisation of secondary organs. In light of the pro metastasis function, many strategies are currently being explored to antagonise the TGF-beta pathway as a treatment for metastatic cancers. Strategies such as using large molecule ligand traps, reducing the translational efficiency of TGF beta ligands using antisense technology, and antagonising TGF-beta receptor I/II kinase function using small molecule inhibitors are the most prominent methods being explored today. Administration of anti-TGF-beta therapies alone, or in combination with immunosuppressive or cytotoxic therapies, has yielded promising results in the preclinical and clinical settings. Despite these successes, the temporal- and context-dependent roles of TGF-beta signalling in cancer has made it challenging to define patient subgroups that are most likely to respond, and the therapeutic regimens that will be most effective in the clinic. Novel mouse models and diagnostic tools are being developed today to circumvent these issues, which may potentially expedite anti-TGF-beta drug development and clinical application. PMID- 20307968 TI - Function of inhibition in visual cortical processing. AB - Although sensory processing in V1 has been extensively characterized, the role of GABAergic inhibition is still not well understood. Advances in molecular biology have now removed significant barriers to the direct investigation of inhibitory processes in vivo. Recent studies have provided important insights into the influence of GABAergic inhibition on cortical processing at both the single cell level, where inhibition helps to shape cortical receptive fields, and at the network level, where inhibition is critical for generating cortical oscillations and setting network state. PMID- 20307970 TI - Cancer metastasis as a therapeutic target. AB - Despite many years of basic and clinical research aimed at curbing tumour growth, metastasis remains the prime reason why cancer patients succumb to their disease. Effective translational research is urgently required, yet is not always easy to achieve. Here we review reasons why metastasis as a disease process has proven difficult to control, and suggest ways in which translational research in this area can be strengthened and advanced. PMID- 20307971 TI - Vascular encasement as element of risk stratification in abdominal neuroblastoma. AB - BACKGROUND: Vascular encasement of major vessels has been introduced as element of image defined risk factors (IDRF) for stratification of abdominal neuroblastoma. Some subgroups of this tumor entity are still subject of discussion regarding surgical approach and radicality. Aim of this study was to analyse a cohort of related patients. PATIENTS AND METHODS: Children operated on for neuroblastoma with encasement of major abdominal vessels (April 2002-April 2009) were retrospectively evaluated regarding surgical procedures, intra- and postoperative complications, and outcome. RESULTS: There were 18 patients with abdominal NB and encasement of major vessels. Mean age at operation was 43.5 months (2.5-113), mean operation time was 228 minutes (157-428). Complete macroscopic tumor resection was realised in 14 children. Vascular reconstruction was necessary in 5 patients. Tumor progression/relapses requiring further operation occurred in 3 patients. Major postoperative complications were 1 loss of unilateral renal function with subsequent nephrectomy, 1 renal vein thrombosis (operative revision), 1 renal artery embolism (operative revision), and 1 ureteral obstruction (stenting). Mean follow up was 34.8 months (2-78). CONCLUSIONS: Vascular encasement as part of IDRF is a valuable tool for stratification of abdominal NB. Surgery of NB with vascular encasement includes divers and complex procedures. Children seem to benefit from complete tumor resection or at least relevant tumor reduction although operations can mean a relevant strain for the patients. PMID- 20307972 TI - The pyrolytic degradation of wood-derived lignin from pulping process. AB - Lignin is a key component in the biomass with a complex polymeric structure of the phenyl-C(3) alkyl units. The kraft lignin from the wood pulping process is tested in TG-FTIR and Py-GC-MS. The samples are pyrolyzed in TGA coupled with FTIR from 30 to 900 degrees C at the heating rate of 20 and 40K/min. The evolution of phenolic compounds in the initial pyrolysis stage of lignin is determined by FTIR, while the second stage is mainly attributed to the production of the low molecular weight species. A bench-scale fast pyrolysis unit is employed to investigate the effect of temperature on the product yield and composition. It is found that the guaiacol-type and syringol-type compounds as the primary products of lignin pyrolysis are predominant in bio-oil, acting as the significant precursors for the formation of the derivatives such as the phenol-, cresol- and catechol-types. A series of free-radical chain-reactions, concerning the cracking of different side-chain structures and the methoxy groups on aromatic ring, are proposed to demonstrate the formation pathways for the typical compounds in bio-oil by closely relating lignin structure to the pyrolytic mechanisms. The methoxy group (-OCH(3)) is suggested to work as an important source for the formation of the small volatile species (CO, CO(2) and CH(4)) through the relevant free radical coupling reactions. PMID- 20307973 TI - Dependence on the properties of organic solvent: study on acyl migration kinetics of partial glycerides. AB - During Rhizopus oryzae-mediated methanolysis of triglycerides for biodiesel production, the amount of 1,2-DG and 2-MG as well as the ratio of 1,2-DG/1,3-DG and 2-MG/1-MG differed significantly in different reaction medium, which indicated that solvent might be a crucial factor that would influence the acyl migration rate, leading to varied biodiesel yield. In this paper, the influence of solvent and their properties on acyl migration kinetics of both 1,2 diglyceride and 2-monoglyceride were investigated systematically. It was found that decreasing solvent polarity would give increasing acyl migration rate constants in general. Solvent polarity influenced the acyl migration rate through the influence of the charge dispersion of the transition state. High polarity of the solvent was unfavorable to the transition state charge dispersion, which would increase its energy state, and thus decreased the acyl migration rate and then led to relatively lower methyl ester yield. PMID- 20307974 TI - Removal of organic substances and oxidation of ammonium nitrogen by a down-flow hanging sponge (DHS) reactor under high salinity conditions. AB - A down-flow hanging sponge (DHS) reactor, constructed by connecting three identical treatment units in series, was fed with highly saline artificial coke plant wastewater containing 1400 mg L(-1) of phenol in terms of chemical oxygen demand (COD) and 500 mg-NL(-1) of ammonium nitrogen. The COD was removed by the 1st unit, achieving 92% removal at an average COD loading rate of 3.0 kg-COD m( 3)d(-1) for all units, with oxidation of ammonium nitrogen occurring primarily in the two downstream units. Microbial assays of the different units of the reactor revealed greater numbers of nitrifying bacteria in the 2nd and 3rd units than in the 1st unit, corresponding with the observed ammonium oxidation pattern of the reactor. These findings suggest that a succession of microflora was successfully established along the DHS. PMID- 20307975 TI - Enzymatic saccharification of biologically pre-treated wheat straw with white-rot fungi. AB - Wheat straw was submitted to a pre-treatment by the basidiomycetous fungi Euc-1 and Irpex lacteus, aiming to improve the accessibility of cellulose towards enzymatic hydrolysis via previous selective bio-delignification. This allowed the increase of substrate saccharification nearly four and three times while applying the basidiomycetes Euc-1 and I. lacteus, respectively. The cellulose/lignin ratio increased from 2.7 in the untreated wheat straw to 5.9 and 4.6 after the bio treatment by the basidiomycetes Euc-1 and I. lacteus, respectively, thus evidencing the highly selective lignin biodegradation. The enzymatic profile of both fungi upon bio-treatment of wheat straw have been assessed including laccase, manganese-dependent peroxidase, lignin peroxidase, carboxymethylcellulase, xylanase, avicelase and feruloyl esterase activities. The difference in efficiency and selectivity of delignification within the two fungi treatments was interpreted in terms of specific lignolytic enzyme profiles and moderate xylanase and cellulolytic activities. PMID- 20307976 TI - DSC studies to evaluate the impact of bio-oil on cold flow properties and oxidation stability of bio-diesel. AB - This paper describes the use of Differential Scanning Calorimetry (DSC) to evaluate the impact of varying mix ratios of bio-oil (pyrolysis oil) and bio diesel on the oxidation stability and on some cold flow properties of resulting blends. The bio-oils employed were produced from the semi-continuous Auger pyrolysis of pine pellets and the batch pyrolysis of pine chips. The bio-diesel studied was obtained from poultry fat. The conditions used to prepare the bio oil/bio-diesel blends as well as some of the fuel properties of these blends are reported. The experimental results suggest that the addition of bio-oil improves the oxidation stability of the resulting blends and modifies the crystallization behavior of unsaturated compounds. Upon the addition of bio-oil an increase in the oxidation onset temperature, as determined by DSC, was observed. The increase in bio-diesel oxidation stability is likely to be due to the presence of hindered phenols abundant in bio-oils. A relatively small reduction in DSC characteristic temperatures which are associated with cold flow properties was also observed but can likely be explained by a dilution effect. PMID- 20307977 TI - Phosphate-limitation mediated lipid production by Rhodosporidium toruloides. AB - Nitrogen-limited conditions have been routinely prepared for efficient lipid production by oleaginous microorganisms. However, it is difficult to attain high cellular lipid contents with natural nitrogen-rich substrates. In the present study, we showed that lipid accumulation by Rhodosporidium toruloides Y4 was directly linked to the carbon to phosphorus (C/P) molar ratios of the culture media. Moreover, such lipid accumulation phenomena were effective regardless of the presence of high amounts of nitrogen sources. Thus, cellular lipid content and lipid yield were 62.2% and 0.205 g/g glucose, respectively, using a medium with a carbon to nitrogen (C/N) molar ratio of 6.1 and a C/P molar ratio of 9552. This work suggested that phosphorus limitation can be equally effective and efficient to mediate lipid accumulation, which in turn, provides opportunities to produce microbial lipid more economically using natural or waste materials with high nitrogen content. PMID- 20307978 TI - Biomimetic soy protein nanocomposites with calcium carbonate crystalline arrays for use as wood adhesive. AB - Despite the biodegradability, non-toxicity, and renewability, commercially available soy protein-based adhesives still have not been widely adopted by industry, partially due to their disappointing performances, i.e., low glue strength in the dry state and no glue strength in the wet state. In this study, biomimetic soy protein/CaCO(3) hybrid wood glue was devised and an attempt made to improve the adhesion strength. The structure and morphology of the adhesive and its fracture bonding interface and adhesion strength were investigated. Results showed that the compact rivets or interlocking links, and ion crosslinking of calcium, carbonate, hydroxyl ions in the adhesive greatly improving the water-resistance and bonding strength of soy protein adhesives. Glue strength of soy protein hybrid adhesive was higher than 6 MPa even after three water-immersion cycles. This green and sustainable proteinous hybrid adhesive, with high glue strength and good water-resistance, is a good substitute for formaldehyde wood glues. PMID- 20307979 TI - Synthesis and bioluminescence-inducing properties of autoinducer (S)-4,5 dihydroxypentane-2,3-dione and its enantiomer. AB - The autoinducer (4S)-4,5-dihydroxypentane-2,3-dione ((S)-DPD, AI-2) facilitates chemical communication, termed 'quorum sensing', amongst a wide range of bacteria, The synthesis of (S)-DPD is challenging in part due to its instability. Herein we report a novel synthesis of (S)-DPD via (2S)-2,3-O-isopropylidene glyceraldehyde, through Wittig, dihydroxylation and oxidation reactions, with a complimentary asymmetric synthesis to a key precursor. Its enantiomer (R)-DPD, was prepared from d-mannitol via (2R)-2,3-O-isopropylideneglyceraldehyde. The synthesized enantiomers of DPD have AI-2 bioluminescence-inducing properties in the Vibrio harveyi BB170 strain. PMID- 20307980 TI - B-Raf kinase inhibitors: hit enrichment through scaffold hopping. AB - In continuation of our efforts toward hit identification and optimization for a B Raf kinase project, we have employed a scaffold hopping strategy. The original HTS hit scaffold pyrazolo[1,5-a]pyrimidine was replaced with different thienopyrimidine and thienopyridine scaffolds to append the optimal pharmacophore moieties in order to generate novel B-raf kinase inhibitors with desirable potency and properties. This strategy led to the identification of additional lead compound 11b which had good enzyme and cell potency, while maintaining selectivity over a number of kinases. PMID- 20307981 TI - Rational design of a pirinixic acid derivative that acts as subtype-selective PPARgamma modulator. AB - Peroxisome proliferator-activated receptor gamma (PPARgamma) is involved in glucose and lipid homeostasis. PPARgamma agonists are in clinical use for the treatment of type 2 diabetes. Lately, a new class of selective PPARgamma modulators (SPPARgammaMs) was developed, which are believed to show less side effects than full PPARgamma agonists. We have previously shown that alpha substitution of pirinixic acid, a moderate agonist of PPARalpha and PPARgamma, leads to low micromolar active balanced dual agonists of PPARalpha and PPARgamma. Herein we present modifications of pirinixic acid leading to subtype-selective PPARgamma agonists and furthermore the development of a selective PPARgamma modulator guided by molecular docking studies. PMID- 20307982 TI - Identification of very potent inhibitor of human aminopeptidase N (CD13). AB - In this Letter we describe broad comparision studies toward rat, pig, and human aminopeptidase N (CD13) orthologs using phosphinate inhibitors related in structure to hydroxamic acids. This SAR approach yielded a very potent inhibitor of human aminopeptidase N: alpha(1)-amino-3-phenylpropyl(alpha(2)-hydroxy-3 phenylpropyl)phosphinic acid with an IC(50)=60 nM. PMID- 20307983 TI - A 3 months mild functional test regime does not affect disease parameters in young mdx mice. AB - To assess the effect of potential therapeutic agents in dystrophic mice it is useful to have a functional test regime that does not affect the natural disease progression of mdx mice with dystrophinopathy. We determined the effect of a 12 week test regime consisting of fore limb grip strength, rotarod analysis and two and four limb hanging wire tests on the disease progression of 4-week-old mdx mice. Mice performed the different functional tests on consecutive days on a weekly basis. No difference was found in serum creatine kinase levels between functionally active and sedentary mice. The percentage of fibrotic/necrotic areas assessed in a semi-automated way with colour deconvolution of skeletal muscles, heart and diaphragm did not vary within muscles or between groups, nor did the gene expression levels of disease-related genes. We conclude that this test regime may be suitable for short-term functional evaluation of therapeutic approaches in the mdx mouse. PMID- 20307984 TI - Synthesis and biological evaluation of 4-(hydroxyimino)arylmethyl diarylpyrimidine analogues as potential non-nucleoside reverse transcriptase inhibitors against HIV. AB - A series of novel diarylpyrimidine analogues featuring a hydroxyiminomethyl group between the pyrimidine scaffold and the aryl wing I have been synthesized and tested in MT-4 cells culture as non-nucleoside reverse transcriptase inhibitors against human immunodeficiency virus (HIV). Most of these new congeners exhibited moderate to excellent activity against wild-type virus with an EC(50) value ranging from 0.569microM to 0.005microM. 4-(4-((Hydroxyimino) (3 methoxyphenyl)methyl)pyrimidin-2-ylamino)benzonitrile (12n) was identified as the most active compound of this new series (EC(50)=0.025microM, SI >1223) associated with moderate activity against HIV-1 double mutant strains (K103N+Y181C) (EC(50)=8.72microM) in addition to its anti-HIV-2 activity with an EC(50) value of 8.31microM. Preliminary structure-activity relationship (SAR) among the newly synthesized DAPYs was also investigated. PMID- 20307985 TI - Aspects of thermal martensite in a FeNiMnCo alloy. AB - Thermal martensite characteristics in Fe-29%Ni-2%Mn-2%Co alloy were investigated with scanning electron microscopy (SEM) and Mossbauer spectroscopy characterization techniques. SEM observations obviously revealed the lath martensite morphology in the prior austenite phase of examined alloy. As well, the martensitic transformation kinetics was found to be as athermal type. On the other hand, Mossbauer spectroscopy offered the paramagnetic austenite phase and ferromagnetic martensite phase with their volume fractions. Also, the internal magnetic field of the martensite was measured as 32.9T from the Mossbauer spectrometer. PMID- 20307986 TI - Solar UV exposures measured simultaneously to all arbitrarily oriented leaves on a plant. AB - The possible ramifications of climate change include the influence it has upon the amount of cloud cover in the atmosphere. Clouds cause significant variation in the solar UV radiation reaching the earth's surface and in turn the amount incident on ecosystems. The consequences of changes in solar UV radiation delivered to ecosystems due to climate change may be significant and should be investigated. Plants are an integral part of the world wide ecological balance, and research has shown they are affected by variations in solar UV radiation. Therefore research into the influence of solar UV radiation on plants is of particular significance. However, this requires a means of obtaining detailed information on the solar UV radiation received by plants. This research describes a newly developed dosimetric technique employed to gather information on solar UV radiation incident to the leaves of plants in combination with the measurement of spectral irradiances in order to provide an accurate method of collecting detailed information on the solar UV radiation affecting the canopy and lower leaf layers of individual plants. Variations in the measurements take into account the inclination and orientation of each leaf investigated, as well as the influence of shading by other leaves in the plant canopy. PMID- 20307987 TI - Quality improvement guidelines for percutaneous transhepatic cholangiography, biliary drainage, and percutaneous cholecystostomy. PMID- 20307988 TI - Excimer laser-assisted retrieval of Gunther Tulip vena cava filters: a pilot study in a canine Model. AB - PURPOSE: Although most Gunther Tulip filters (GTFs) can be safely retrieved within a few months after implantation, their recommended safe retrieval period is within a few weeks. This study aims to assess the feasibility of excimer laser assisted retrieval of GTFs incorporated into the inferior vena cava (IVC) wall in a canine model. MATERIALS AND METHODS: Six GTFs were implanted in six mongrel dogs and retrieved after four weeks. The retrieval system consisted of a 14-F excimer laser sheath, an 8-F guide catheter, and a 15-mm Goose Neck snare. RESULTS: All filters were tightly fixed to the IVC wall. After ablation of the adhesions by excimer laser emission, all filters were successfully retrieved. Final cavography after retrieval revealed no caval damage except for minor extravasation in three dogs. Examination of the caval specimen taken from a dog immediately after filter retrieval revealed partial absence of the intima and media. In the remaining five dogs, cavography performed 2 days after filter retrieval revealed complete hemostasis and almost indistinguishable intimal indentations. On follow-up cavography 28 days after filter retrieval, caval stenosis with 38% +/- 11% diameter narrowing was noted. The caval specimen obtained from a dog at 28 days showed neointima formation at the level where the filter struts were in contact with the caval wall. The other four dogs have survived for more than 3 months without any adverse events. CONCLUSIONS: Laser assisted retrieval of a GTF incorporated into the IVC wall is feasible in dogs. PMID- 20307989 TI - Utility of iodinated contrast medium in hydrodissection fluid when performing renal tumor ablation. AB - In 21 patients undergoing percutaneous renal tumor ablation, hydrodissection with use of a mixture of 5% dextrose in water and iodinated contrast medium was performed to prevent thermal injury to adjacent structures. This technique allows for the movement of adjacent organs as well as improved differentiation among the hydrodissection fluid, renal tumor, and adjacent tissues. PMID- 20307990 TI - Transjugular intrahepatic portosystemic shunt creation using a transjugular and ultrasound-guided percutaneous approach in a liver transplant recipient. PMID- 20307991 TI - Endovascular temporary vessel occlusion with a reverse-thermosensitive polymer for bloodless minimally invasive renal surgery. AB - PURPOSE: To demonstrate the feasibility of reversible vessel embolization with angiographic guidance for delivery of a rapid reverse-thermosensitive polymer to provide hemostasis as an aid for minimally invasive renal surgery in a porcine model. MATERIALS AND METHODS: After isolation of the left kidney of seven anesthetized pigs (50-70 kg) with a surgical robot, a renal angiogram of both kidneys was obtained. A 5-F angiographic catheter was used to selectively embolize a lower-pole segmental artery of the right and left kidney with a thermosensitive polymer (LeGoo-XL). Distal and proximal embolization of the target vessel was compared. Degree and duration of hemostasis and reversibility was determined. After complete hemostasis was obtained angiographically, a partial robotic lower-pole nephrectomy was performed on the left kidney only. RESULTS: Only proximal embolization provided controllable hemostasis. A 20% polymer concentration in a buffer solution of 40% saline solution and 40% iodine contrast medium by weight injected at room temperature resulted in a reproducible embolus for more than 30 minutes, the time needed to perform a partial nephrectomy. The radiographic appearance of the embolus was used to determine the total amount of polymer needed. Cold saline solution completely dissolved any residual polymer at the end of surgery. CONCLUSIONS: Proximal arterial occlusion with a thermosensitive polymer can be rapidly reversed with selective intraarterial infusion of chilled saline solution. Preceding nephron-sparing surgery with transcatheter embolization of the relevant branch of the renal artery with the polymer can facilitate the procedure and ought to be investigated further. PMID- 20307992 TI - Tunneled pleural catheters for treatment of recurrent malignant pleural effusion following failed pleurodesis. AB - PURPOSE: To evaluate patient outcomes when tunneled pleural drainage catheters are placed for symptomatic, recurrent malignant pleural effusion following failed chemical pleurodesis. MATERIALS AND METHODS: Two hundred seventy patients who underwent placement of a tunneled pleural catheter between January 2002 and December 2006 were retrospectively identified by reviewing interventional radiology billing records with institutional review board approval. Of these 270 patients, 63 (68 hemithoraces; 44 women, 19 men) with dyspnea were referred for tunneled pleural drainage catheter placement following failed pleurodesis for malignant pleural effusion. Clinical and procedural details were identified by chart review. Endpoints were technical success, symptomatic improvement in dyspnea, time to hospital discharge, and time to catheter removal or time to death with the catheter in place. RESULTS: Clinical improvement in dyspnea was noted in 60 of the 63 patients (95%). Fifty-seven of the 63 patients (90%) were discharged with their catheter in place after a median of 3 days (range, 0-29 days). Twenty-seven of the 63 patients (43%) were discharged in 2 days or less. Stays longer than 2 days were all associated with treatment of other medical problems. Twenty-one of the 68 catheters (31%) required fibrinolytic therapy for optimal evacuation of complex pleural collections. Eleven of the 68 catheters (16%) could subsequently be removed due to durable resolution of pleural effusion. The remaining patients died with catheters in place and no clinical evidence of catheter dysfunction after a median of 58 days. CONCLUSIONS: Even following failed pleurodesis, recurrent malignant pleural effusions can be effectively managed with placement of tunneled pleural catheters. PMID- 20307993 TI - Influence of pain reduction by transcutaneous electrical nerve stimulation (TENS) on somatosensory functions in patients with painful traumatic peripheral partial nerve injury. AB - Following peripheral nerve injury sensory loss is taken as a sign of denervation. However, based on reports of improved sensitivity following relief of pain it has been suggested that a functional block produced by the activity in the nociceptive system itself may be responsible for at least part of the sensory aberrations. The aim was to examine if pain reduction by high-frequency TENS influenced somatosensory functions in patients with long-term unilateral painful traumatic peripheral partial nerve injury. Eighteen patients with spontaneous ongoing pain and a touch sensation in the innervation territory of the injured nervous structure of at least 5 on an intensity 11-point Likert rating scale compared with contralaterally, participated. Before and following 80 Hz TENS with a stimulus intensity generating non-painful paresthesiae in the painful areas during 30 min the pain intensity was rated on a numerical rating scale and bedside examination of somatosensory functions (BE) and quantitative sensory testing (QST) were performed in the same areas. Before and following TENS there was no difference in sensory functions between nine patients with >= 50% pain reduction and nine patients with a smaller or no reduction in pain. Compared to baseline, only minor TENS-induced alterations in somatosensory functions were found at BE in conjunction with decreased sensitivity to light touch at QST (p < 0.01) in both groups alike. In conclusion >= 50% pain reduction by TENS did not alter sensory functions differentially compared to a smaller or no reduction in pain. PMID- 20307994 TI - Maple syrup urine disease: further evidence that newborn screening may fail to identify variant forms. AB - Newborn screening (NBS) by tandem mass spectrometry (MS/MS) has allowed for early detection and initiation of treatment in many patients with maple syrup urine disease (MSUD) (OMIM 248600), however, a recent report suggests that variants forms may be missed. Information on these patients is limited. We present clinical, biochemical and molecular information on patients with variant forms of MSUD not detected by the California Newborn Screening Program. Between July 2005 and July 2009, 2200,000 newborns were screened in California by MS/MS. Seventeen cases of MSUD were detected and three (two siblings) were missed. Additionally, the NBS cards of two siblings with late onset MSUD, who were born pre-expanded NBS, were retrospectively analyzed. None of the five patients met criteria to be considered presumptive positive for MSUD (leucine>200micromol/L and a ratio of leucine/alanine>or=1.5). Alloisoleucine (allo-ile) was subsequently analyzed in the NBS cards of all five patients, two of whom were found to have elevated levels. The proband in each family was diagnosed following symptoms triggered by an intercurrent illness or increased protein intake. At diagnosis, leucine levels ranged between 561 and >4528micromol/L, and allo-ile ranged from 137 to 239micromol/L. Two affected siblings had normal plasma amino acids when asymptomatic; however, their biochemical profiles were diagnostic of MSUD during intercurrent illnesses. The median age at diagnosis of all patients was one year (range 0.8-6.7). Heterozygous BCKDHB (E1beta) mutations (c.832G>A/c.970C>T) were identified in one family and a homozygous DBT (E2) sequence variant (c.1430 T>G) in another. The third family had one identifiable DBT mutation (c.827T>G), however, a second mutation was not detected. This report provides further evidence that NBS by MS/MS is unable to detect all cases of MSUD. Second-tier testing with allo-ile may improve sensitivity; however, some children with variant forms will invariably be missed. PMID- 20307995 TI - The obese phenotype-inducing N82K mutation in human leptin disrupts receptor binding and biological activity. AB - A novel homozygous mutation of the leptin gene was recently reported in an Egyptian child and his sister with severe early onset obesity. This mutation results from the substitution of asparagine (AAC) by lysine (AAA) at codon 103 of a non-mature (signal peptide-containing) leptin and corresponds to the N82K mutation in the mature protein. The patient had very low serum leptin levels, raising the question of whether the obese phenotype resulted from low leptin levels or from its lower intrinsic activity. To answer this question, we characterized the functional consequences of the N82K mutation. Wild-type (WT) human leptin was mutated accordingly, expressed in Escherichia coli at high yield, purified to homogeneity as a monomer and compared to WT human leptin prepared by the same methodology. Circular dichroism analysis of the mutated leptin indicated proper refolding and a secondary structure identical to that of the WT human leptin. In contrast to WT human leptin, the N82K mutant did not form a detectable complex with human leptin-binding domain (hLBD) and its binding capacity to hLBD assessed in a nonradioactive receptor-binding assay was at least 500-fold lower than that of WT human leptin. The biological activity of the N82K mutant, tested in two cell bioassays, was reduced by more than three orders of magnitude relative to WT human leptin. Therefore, though the present report does not explain the reason for the low circulating leptin levels it definitely documents that the reported obese phenotype originates not only from low serum leptin levels but also from the N82K mutant's almost total lack of intrinsic leptin activity. PMID- 20307996 TI - "Overcoming barriers: new developments and future directions for urea cycle disorders.". Introduction. PMID- 20307997 TI - Pseudomuscular male with seizures: disseminated cysticercosis. PMID- 20307998 TI - High ferritin levels are associated with hepatosplenic candidiasis in hematopoietic stem cell transplant candidates. AB - OBJECTIVES: Invasive fungal infections (IFI) are a significant cause of morbidity and mortality in hematopoietic stem cell transplant (HSCT) recipients. Hepatosplenic candidiasis (HSC) is defined as a distinct form of invasive candidiasis, with liver, spleen, and kidney involvement, in patients with hematological disorders. METHODS: The charts of 255 patients (male/female 168/87; median age 35 (range 16-71) years) who were evaluated pre-HSCT at the Gazi University Hospital Stem Cell Transplantation Unit between 2003 and 2008, were retrospectively reviewed. RESULTS: HSC, which was demonstrated in six (2.3%) patients, was found to be more common in allogeneic HSCT recipients than in autologous HSCT recipients and in patients who had received two or more previous chemotherapy courses than in patients who had received fewer than two (p>0.05). Patients with HSC tended to have a worse performance status than patients without HSC according to the World Health Organization (p=0.001) and Karnofsky scale (p=0.007). Pre-transplantation ferritin (p=0.008) and acute phase reactant levels, including erythrocyte sedimentation rate (p=0.025) and C-reactive protein (p=0.007), were significantly higher in patients with HSC than in patients without HSC. CONCLUSIONS: This study shows the predictive role of pre transplantation ferritin levels in selecting a subset of patients at increased risk for HSC. Pre-transplantation risk assessment and targeted strategies might lower the morbidity and mortality of IFI in HSCT recipients. PMID- 20307999 TI - Minimally invasive post-mortem CT-angiography in a case involving a gunshot wound. AB - Non-contrast post-mortem computed tomography (pm-CT) is useful in the evaluation of bony pathologies, whereas minimally invasive pm-CT-angiography allows for the detection of subtle vascular lesions. We present a case of an accidentally self inflicted fatal bullet wound to the chest where pm-CT-angiography revealed a small laceration of the anterior interventricular branch of the left coronary artery and a tiny disruption of the right ventricle with pericardial and pleural effusion. Subsequent autopsy confirmed our radiological findings. Post-mortem CT angiography has a great potential for the detection of vascular lesions and can be considered equivalent to autopsy for selected cases in forensic medicine. PMID- 20308000 TI - Degradation of phenol using a combination of ultrasonic and UV irradiations at pilot scale operation. AB - In the present work, combination of ultraviolet (UV) irradiations (using 8 W UV tube) with ultrasonic (US) irradiations (rated power 1 kW and frequency of 25 kHz) has been investigated for the degradation of phenol at pilot scale of operation. Different modes of operation viz. UV alone, US alone, UV/US, UV/TiO(2) (photocatalysis), UV/H(2)O(2), UV/NaCl, UV/US/TiO(2) (sonophotocatalysis) and H(2)O(2) assisted sonophotocatalysis have been investigated with an objective of maximizing the extent of phenol degradation. Effect of presence of hydrogen peroxide and sodium chloride at a concentration of 10 g/l and TiO(2) over a range of 0.5-2.5 g/l has been investigated. It has been observed that 2.0 g/l of TiO(2) is the optimum concentration, beyond which a decrease in the extent of degradation is observed. Maximum extent of degradation of phenol was 37.75% for H(2)O(2) assisted photosonocatalysis at pH of 2. The present work is first of its kind to report the use of combined ultrasonic and UV irradiations at pilot scale operation and obtained results should induce some degree of certainty in proposed industrial applications of sonochemical reactors for wastewater treatment. PMID- 20308001 TI - Second primary tumours in oral cancer. AB - Second primary tumours in patients treated for oral cancer occur at a rate of 3% to 7% per year. The majority of these tumours show up at least six months after the detection of the primary and are often located in the upper aerodigestive tract. Cessation of smoking habits may reduce the risk of the development of a second primary. There is no statistical significance between the oral subsite of the primary and the occurrence of a second primary. There are conflicting views in the literature on the survival rate of patients treated for a second primary in the head and neck region. PMID- 20308002 TI - Quality of life perspectives in patients with oral cancer. AB - This article is set in the context of the oral healthcare team caring for patients following oral cancer treatment. It provides an overview of the definition of quality of life (QoL), how it is measured, the key issues for patients with respect oral cancer, and comment about the role of the dental multidisciplinary team. It provides a source of relevant literature specific to this topic. PMID- 20308003 TI - TGFbeta1 genetic polymorphism is associated with survival in head and neck squamous cell carcinoma independent of the severity of chemoradiotherapy induced mucositis. AB - Chemoradiotherapy (CRT) of head and neck squamous cell carcinoma (HNSCC) is often accompanied by severe mucosal reactions. We have recently shown that the single nucleotide polymorphism (SNP) rs1982073 of the TGFbeta1 gene (TGFB1) is associated with the survival of HNSCC patients who have undergone CRT. In order to evaluate possible mechanisms mediating this, we investigated if the TGFB1 polymorphism was associated with the severity of mucositis induced by CRT. Peripheral blood DNA of 34 HNSCC patients who had undergone CRT was genotyped for the SNP rs1982073 of the TGFB1. Mucositis was graded according to acute toxicity criteria of radiation therapy oncology group (RTOG). The mean follow-up time was 48 months (range, 4-115 months). We did not find a significant association between the TGFB1 polymorphism and the degree of acute mucositis (OD=2.65; 95% CI 0.50-13.89; p=0.25). The degree of acute mucositis was not connected to disease free survival (p=0.35). However, the TGFB1 polymorphism was associated with survival irrespective of the degree of mucositis (HR=3.23; 95% CI 1.19-8.77; p=0.02). PMID- 20308004 TI - Changes of symptoms and depression in oral cavity cancer patients receiving radiation therapy. AB - The purposes of this study were to (1) examine changes in symptom severity and depression within 3 months of first undergoing radiation therapy (RT) or concurrent chemoradiation therapy (CCRT), and (2) identify factors involved in changes in symptom severity in newly diagnosed oral cavity cancer patients undergoing post-operative RT or CCRT. A prospective panel survey was conducted to assess changes in symptoms, depression, and disease- or treatment-related characteristics within 3 months of beginning RT or CCRT (pre-treatment and 1, 2, and 3 months from first receiving RT). A total of 76 eligible oral cavity cancer patients were recruited from the outpatient radiation department of a medical center in northern Taiwan. The results showed mild-to-moderate overall symptom and depression levels during treatment, with the five most distressing symptoms being swallowing difficulty, poor appetite, oral mucositis, pain, and fatigue. The severity of symptoms and depression peaked at approximately 2 months from beginning RT or CCRT (T3). Changes in overall symptom severity were found to be significantly related to patients' radiation dose and depression level. These results can help advance understanding of changes in symptoms and facilitate prevention and management of symptoms associated with RT or CCRT. Psychological distress, particularly, depression, requires careful monitoring and management in oral cavity cancer patients undergoing RT or CCRT. PMID- 20308005 TI - Potentially malignant disorders of the oral and oropharyngeal mucosa; present concepts of management. AB - In spite of tremendous progress in the field of molecular biology there is yet no single marker that reliably predicts malignant transformation of a potentially malignant disorder of the oral mucosa. Therefore, it is recommended to excise or laser any oral of oropharyngeal leukoplakia/erythroplakia, if feasible, irrespective of the presence or absence of dysplasia. However, it is actually unknown whether such removal truly prevents the possible development of a squamous cell carcinoma. Therefore, lifelong follow-up is recommended at intervals of no more than 6 months. At present, oral lichen planus is more or less accepted as being a potentially malignant disorder. There are no means to prevent such event. The efficacy of follow-up of oral lichen planus is questionable. PMID- 20308006 TI - Primary tumor induces sentinel lymph node lymphangiogenesis in oral squamous cell carcinoma. AB - The main factor that affects the prognosis of patients with oral squamous cell carcinoma (OSCC) is regional lymph node metastases, which usually spreads first to the sentinel lymph nodes (SLNs). Recent studies have demonstrated that tumor cells in several malignancies can induce lymphangiogenesis in SLNs before metastasizing. To elucidate the mechanisms of tumor dissemination of OSCC, we investigated whether primary tumors induce lymphangiogenesis within SLNs in patients with OSCC. The mRNA expression of lymphatic-specific markers, including VEGFR-3, Prox-1, and LYVE-1 in 23 metastasis-negative SLNs obtained from 10 patients with OSCC, was investigated using a quantitative real-time RT-PCR assay, and compared with control lymph nodes from patients with non-cancerous diseases. In addition, VEGF-C and VEGF-D expressions of the primary tumor were examined by immunohistochemistry. In SLNs, there were highly significant correlations between the three lymphatic markers examined. Interestingly, the level of LYVE-1 expression in SLNs, despite the absence of metastasis, was significantly higher than in control lymph nodes. Moreover, SLNs from patients with VEGF-C-positive tumor showed a significantly higher expression of VEGFR-3 than those from patients with VEGF-C-negative tumor. Our findings suggest that in OSCC, the primary tumor actively induces lymphangiogenesis in SLNs prior to the onset of metastases, and where tumor-derived VEGF-C plays an important role. PMID- 20308007 TI - Oral and dental health care of oral cancer patients: hyposalivation, caries and infections. AB - Oral cancer and its treatment can cause a variety of problems to patients, also as regards maintaining their daily oral hygiene. Surgery mutilates tissues which may hamper cleaning the teeth and mucosal surfaces. The patient may have complicated reconstructive structures that also need continuous attention. Radiotherapy-induced hyposalivation further complicates the situation and decreases the quality of life. Consequently, dental caries, mucosal diseases such as candidosis and sialadenitis become problematic to treat. Hence every effort should be focused on prevention. In caries prevention intensified fluoride therapy together with dietary counseling is needed. Oral cancer patients also need to be frequently referred to dental hygienists for professional cleaning. Drinking enough daily and moisturizing mucosal surfaces with commercial dry-mouth products, vegetable oils, milk products and respective topical agents need to be individually recommended. In addition, patients with severe dry mouth cases may also benefit from the prescription of pilocarpine tablets. In oral candidosis, the microbiological diagnosis must be confirmed before administration of antifungal drugs in order to avoid the selection pressure to resistant strains. PMID- 20308008 TI - Early effect of boron neutron capture therapy mediated by boronophenylalanine (BPA-BNCT) on mast cells in premalignant tissue and tumors of the hamster cheek pouch. AB - Mast cell (MC) activation in the hamster cheek pouch cancerization model is associated with the increase in tumor cell proliferation, mediated in turn by tryptase, a protease released from mast cell granules after activation. Tryptase induces tumor cell proliferation through the activation of PAR-2 (protease activated receptor-2) on the plasma membrane of carcinoma cells. The therapeutic success of boron neutron capture therapy mediated by boronophenylalanine (BPA BNCT) in tumor control in the hamster cheek pouch oral cancer model has been previously reported by our laboratory. Early effects of BPA-BNCT on tumors of the hamster cheek pouch include a reduction in DNA-synthesis with the concomitant decrease in the proliferation of malignant cells. The aim of the present study was to investigate the early histological changes in mast cells after BPA-BNCT in tumors and premalignant tissue of the hamster cheek pouch. Tumor-bearing pouches were treated with BPA-BNCT or beam only (neutron irradiation without prior administration of the boron compound) and sacrificed 1day after treatment. The samples were fixed in Carnoy fixative and stained with alcian blue-safranin to identify all the populations of mast cells. Total, active and inactive mast cells (MC) were counted in the connective tissue and the adventitious tissue underlying the pouch wall and at the base of the tumors in pouches treated with BPA-BNCT, in keeping with a previously described technique. BPA-BNCT induced a marked reduction in the total number of mast cells in the pouch (p<0.05). This reduction in the total number of mast cells was due to a reduction in mast cells at the base of the tumor (p<0.005) and it occurred at the expense of the active mast cells (p<0.05). A slight reduction that did not reach statistical significance also occurred in the amount of mast cells in the pouch wall (that corresponds to the premalignant tissue in tumor-bearing pouches), and in the adventitious tissue. In this case the reduction was seen in the inactive population. Both BPA BNCT and beam only elicited a qualitative change in the secretion modality of the granule content. Although further studies are needed to evaluate the subcellular effect of BNCT on mast cell granule secretion, the reduction in cell proliferation induced by BPA-BNCT would be partially due to the decrease in total mast cells in the hamster check pouch. PMID- 20308009 TI - Oral cancer pain. AB - Pain may be the initial symptom in oral cancer, and is a common complaint both in patients awaiting treatment and in those already in treatment. However, little has been published in the literature on the management of oral cancer pain. Effective pain control requires a multimodal approach in which pharmacological management based on the World Health Organization (WHO) analgesic ladder continues to play an essential role. Although different routes are available for the administration of analgesics, oral delivery continues to be the principal route for pain control in the first instance. Interventional approaches include blockade of a peripheral nerve or of the relevant ganglion, and the use of central neuraxial blockade. The intraventricular or intrathecal administration of opioids, with or without local anaesthetics, has been indicated for severe intractable pain. The development of new treatment modalities provides additional options, though further clinical research is required. There is no evidence of the efficacy of non-pharmacological methods such as acupuncture or transcutaneous nerve stimulation in the management of oral cancer pain. Surgery, radiation therapy, and chemotherapy have also been suggested, but their results have not been quantified. PMID- 20308010 TI - Socio-economic factors and stage at presentation of head and neck cancer patients in Ottawa, Canada: a logistic regression analysis. AB - To determine if socio-economic status (SES) affects the stage at presentation of head and neck cancer (HNC) patients in Ottawa, Canada. To determine if the method of diagnosis affects the stage at presentation in these patients. We obtained data on SES, method of diagnosis, and stage at presentation for patients presenting to the head and neck cancer clinic at The Ottawa Hospital Regional Cancer Centre (TORCC). We performed a logistic regression analysis using stage at presentation as the dependent variable. We found no statistically significant association between average family income (by postal code) and stage at presentation. We found that oral cancers presented at a later stage compared with other HNCs but that who made the diagnosis was an important factor. Oral cancers diagnosed by a dentist had 3.44 times the odds of being at a later stage than other HNCs (CI 1.01-11.96), but oral cancers diagnosed by other means had 11.42 times the odds of being at a later stage than other HNCs. We found that male patients presented at a later stage than female patients (OR 2.62, CI 1.03-6.63). Finally, former smokers had about 1/3 the odds of presenting at a later stage than current smokers (OR 0.33, CI 0.13-0.84) although nonsmokers were not significantly less likely than current smokers to present later (OR 0.47, CI 0.17 1.32). We found no evidence that in Ottawa, Canada patients of a lower SES with HNC presented at an different stage than patients with higher SES. We found that patients presenting with oral cancers presented at an earlier stage if they were diagnosed by a dentist. PMID- 20308011 TI - Investigation of the spin-Hamiltonian parameters for the trigonal U5+ center in CaF2 crystal. AB - The spin-Hamiltonian parameters (g factor g(//), g(perpendicular) and hyperfine structure constants A(//), A(perpendicular)) of the trigonal U(5+) center in CaF(2) crystal have been calculated from the complete diagonalization (of energy matrix) method (CDM) for 5f(1) ions in trigonal crystal field and under an external magnetic field. In the calculation, the crystal-field parameters are estimated from the superposition model. From the calculations, these spin Hamiltonian parameters are reasonably explained, and the defect model (i.e., the trigonal U(5+) center is attributed to U(5+) substituting for Ca(2+) in CaF(2) with six F(-) ions replaced by O(2-) and the other two F(-) sites vacant because of charge compensation) given in the previous paper is confirmed. The results are discussed. PMID- 20308012 TI - Melt grafting of metal salts onto LLDPE backbone--an FTIR study. AB - The melt graft functionalization of metal di(meth)acrylates onto linear low density poly(ethylene) (LLDPE) at 160 degrees C under inert atmosphere is reported here. The post melt grafting FTIR-RI method was used to find out the % grafting of metal salts onto LLDPE backbone. Further, DSC, TGA and HRTEM techniques were introduced to explain the results. A plausible reaction mechanism was proposed. PMID- 20308013 TI - The effect of laser wavelength on the Raman Spectra of phenanthrene, chrysene, and tetracene: implications for extra-terrestrial detection of polyaromatic hydrocarbons. AB - Raman spectroscopy, with visible laser (514 and 633 nm) and near infrared (785 and 1064 nm) excitation, has been used to obtain high quality spectra of phenanthrene, chrysene, and tetracene. Samples with dimensions from a minimum size of 10 microm have been analyzed utilizing a Raman microprobe fitted with a charge-coupled device (CCD) array detector and a FT-Raman instrument. Fluorescence is observed for samples using visible 514, 633 and near infrared 785 nm excitation but most of the samples can be measured with a near infrared 1064 nm Nd:YAG laser. PMID- 20308014 TI - DFT (LSDA, B3LYP and B3PW91) comparative vibrational spectroscopic analysis of alpha-acetonaphthone. AB - FT-IR and FT-Raman spectra of alpha-acetonaphthone have been recorded and analyzed. The geometry, fundamental vibrational frequencies and intensity of the vibrational bands are interpreted with the aid of structure optimizations and normal coordinate force field calculations based on density functional theory (DFT) B3PW91/6-311G method and also a comparative studies between different levels and various basis sets combination. The scaled B3PW91/6-11G results are best, even though LSDA/6-311G wavenumbers are well in agreement before scaling. The complete vibrational assignments of wavenumbers are made on the basis of potential energy distribution (PED). The effects due to the substitutions of methyl group and carbon-oxygen bond are investigated. The results of the calculations are applied to simulated spectra of the title compound, which shows excellent agreement with observed spectra. PMID- 20308015 TI - Influence of myristic acid on furosemide binding to bovine serum albumin. Comparison with furosemide-human serum albumin complex. AB - Fluorescence studies on furosemide (FUR) binding to bovine serum albumin (BSA) showed the existence of three or four binding sites in the tertiary structure of the protein. Two of them are located in subdomain IIA, while the others in subdomains IB and/or IIIA. Furosemide binding in subdomain IB is postulated on the basis of run of Stern-Volmer plot indicating the existence of two populations of tryptophans involved in the interaction with FUR. In turn, the significant participation of tyrosil residues in complex formation leads to the consideration of the subdomain IIIA as furosemide low-affinity binding site. The effect of increasing concentration of fatty acid on FUR binding in all studied binding sites was also investigated and compared with the previous results obtained for human serum albumin (HSA). For BSA the lesser impact of fatty acid on affinity between drug and albumin was observed. This is probably a result of more significant role of tyrosines in the complex formation and different polarity of microenvironment of the fluorophores when compared HSA and BSA. The most distinct differences between FUR-BSA and FUR-HSA binding parameters are observed when third fatty acid molecule is bound with the protein and rotation of domains I and II occurs. However these structural changes mostly affect FUR low affinity binding sites. PMID- 20308016 TI - Headache and low platelets in a patient with acute leukemia. PMID- 20308017 TI - Severe thrombocytopenia associated with acute autochthonous hepatitis E. PMID- 20308018 TI - Practice domains in sports medicine and sport science. PMID- 20308019 TI - Knowledge of the professional role of others: a key interprofessional competency. AB - In this paper, the authors present the results of a study which delineated six key competencies of interprofessional collaborative practice for patient-centred care: communication; strength in one's professional role; knowledge of professional role of others; leadership; team function; and negotiation for conflict resolution. While all of these competencies are important and require special attention, this paper examines and discusses the competency knowledge of professional role of others and its associated behavioural indicators, especially as these relate to the interprofessional education of nursing students. The identification of these competencies and their behavioural indicators serve two purposes. It forms the basis for the preparation of students, preceptors, and faculty for interprofessional practice, and it develops a tool for assessing student performance in such practice. Consequently, we believe that the utilization of this key competency and its behavioural indicators will contribute to the development of programs that include specific knowledge and skills related to interprofessional nursing education. This will enable educators to support and evaluate students in interprofessional educational experiences more efficiently and effectively. Ultimately, as nursing students practice and become fully functioning practitioners, client care will be optimized. PMID- 20308020 TI - Purification of lactoferrin using hydroxyapatite. AB - Lactoferrin is an important nutriceutical with various physiological functions. It is present in whey at very low concentrations. This work describes a mixed mode (hydroxyapatite) chromatography method for one-column fractionation of lactoferrin from whey. Lactoperoxidase, a protein with similar molecular weight and isoelectric point, was initially desorbed from the matrix under isocratic conditions. Lactoferrin was obtained in homogeneity without lactoperoxidase activity and free from other major whey proteins such as alpha lactoalbumin and beta lactoglobulin. PMID- 20308021 TI - Comprehensive gas chromatography with Time of Flight MS and large volume introduction for the detection of fluoride-induced regenerated nerve agent in biological samples. AB - Recently, several methods have been developed to verify exposure to nerve agents. Most of these methods, such as the fluoride reactivation technique and the analysis of inhibited phosphonylated butyrylcholinesterase (BuChE), are based on mass spectrometry. The high specificity of the mass spectrometer might also imply a disadvantage, because the acquisition mass, i.e. the identity of the analyte must be known beforehand in order to direct the MS analysis in the most sensitive mode. In real cases, the identity of the nerve agent is not always known beforehand and the mass spectrometer should be operated in a scanning mode, with the consequence that sensitivity of the method will be lower. Comprehensive GC, or GC x GC, is a technique which offers enhanced separation. The implied larger selectivity of the GC separation allows mass spectrometry to be conducted in a less specific, scanning, mode. By the use of this configuration, the identity of the nerve agent does not have to be known beforehand but can be traced. In order to be able to detect lower concentrations and assess lower exposure levels, a large volume injection technique was developed allowing sample sizes up to 100 microL. The technique was tested with plasma samples that had been inhibited with various nerve agents. Subsequently, the cholinesterase-bound nerve agent was regenerated by the fluoride reactivation technique. Using the newly developed comprehensive GC-MS method it was possible to detect nerve agent at an exposure level of 1% BuChE inhibition, which is approximately 70 pg nerve agent/mL. These low exposure levels cannot be verified with a cholinesterase (ChE) activity assay. Moreover, the identity of the regenerated nerve agent was verified by the mass spectrum that was generated by the TOF mass spectrometer. This paper presents a technique able to deliver full-scan data on the analysis of nerve agents in biomedical samples at relevant exposure levels (1% BuChE inhibition). This full-scan data meets for a large part the forensic requirements that are in place for the analysis of biomedical samples in the context of alleged use of Chemical Warfare Agents. PMID- 20308022 TI - Sensitive quantification of sirolimus and everolimus by LC-MS/MS with online sample cleanup. AB - Sirolimus and its derivative everolimus are widely used today as immunosuppressive agents for example in the transplantation medicine. The problematic pharmacokinetic behavior of those substances makes therapeutic drug monitoring mandatory. Therefore, a fast, simple and sensitive high-throughput procedure using online extraction with turbulent flow chromatography for the concurrent measurement of sirolimus and everolimus has been developed. 200 microl of whole blood was mixed with internal standard (23-desmethoxyrapamycin) and the precipitation solution and centrifuged. An aliquot of the supernatant was transferred into autosampler vials. 50 microl of the supernatant was injected into the LC system, where the analytes were extracted using turbulent flow chromatography and thereafter analyzed using reversed phase chromatography. Detection was done by atmospherical pressure chemical ionization (APCI) mass spectrometry in the negative ionization mode. The method has been fully validated and compared to a previously used method. The method was shown to be linear over the entire calibration range (2.2-43.7 microg/l for everolimus and 2.9-51.2 microg/l for sirolimus). The lower limit of quantification was 0.5 microg/l for both compounds. For within-day and between-day analysis, the CV's were <7.6% for everolimus and <8.7% for sirolimus, respectively. The accuracy was between 92.1% and 105% for everolimus and 96.1% and 106% for sirolimus. Recovery ranged between 46.3% and 50.6% for everolimus and 51.2% and 57.2% for sirolimus. The method was demonstrated to be free of matrix effects and comparable to the previously used method. The presented LC-MS/MS method, using turbulent flow chromatography online extraction, allows a fast, simple and reliable determination of everolimus and sirolimus. PMID- 20308023 TI - [Suprasellar mass and diabetes insipidus. A case of lymphocytic infundibuloneurohypophysitis self-limited with steroids]. PMID- 20308025 TI - [Spinal section due to a C7 vertebral body fracture]. PMID- 20308026 TI - [Symptomatic hypocalcaemia due to nutritional rickets. A presentation of two cases]. AB - INTRODUCTION: The nutritional rickets is considered an uncommon disease in developed countries, but the increase in its incidence appears to be related to the increase in the number of immigrants in these countries. Thus in Spain, we must increase our diagnostic suspicion of this disease and be able to detect it, even when it appears with unusual symptoms. We describe two clinical cases of breast-fed babies who presented with symptomatic hypocalcaemia and were diagnosed with rickets. Case 1. A six month-old breast-fed baby who had episodes of tonic seizures and irritability, with no other findings in the physical examination, and diagnosed with secondary hypocalcaemia due to nutritional rickets. Case 2. A seven month-old breast-fed baby who had generalised hypertonia, stridor and irritability, with a normal physical examination, and also diagnosed with hypocalcaemia secondary to rickets. DISCUSSION: The old concept that rickets is a rare condition in our country means that we often tend to rule out this pathology, thus delaying the diagnosis and the treatment. We must review our concepts in order to be able to detect the common and also the unusual symptoms of nutritional rickets. PMID- 20308027 TI - Wide thumb and the first web reconstruction using a neurovascularised instep free flap. AB - Deformed hands result in palmar defects of the thumb. The sensate instep free flap can be used for wide palmar coverage of the thumb. Three hands with palmar defects of the thumb extended to the first web space underwent soft-tissue reconstruction using a neurovascular instep free flap. These flaps provided sensate coverage with static two-point discrimination values of 8-15 mm. Key pinch strengths of reconstructed thumbs were nearly half of those on the normal side. Donor foot morbidity was minimal with no hyperkeratosis. The neurovascular instep free flap supplies sensate, similar pliable and tough glabrous skin to the palmar surface of the thumb extended to the first web area. PMID- 20308024 TI - How to predict a high rate of inappropriateness for upper endoscopy in an endoscopic centre? AB - BACKGROUND: Inappropriateness of upper endoscopy (EGD) indication causes decreased diagnostic yield. Our aim of was to identify predictors of appropriateness rate for EGD among endoscopic centres. METHODS: A post-hoc analysis of two multicentre cross-sectional studies, including 6270 and 8252 patients consecutively referred to EGD in 44 (group A) and 55 (group B) endoscopic Italian centres in 2003 and 2007, respectively, was performed. A multiple forward stepwise regression was applied to group A, and independently validated in group B. A <70% threshold was adopted to define inadequate appropriateness rate clustered by centre. RESULTS: discrete variability of clustered appropriateness rates among the 44 group A centres was observed (median: 77%; range: 41-97%), and a <70% appropriateness rate was detected in 11 (25%). Independent predictors of centre appropriateness rate were: percentage of patients referred by general practitioners (GP), rate of urgent examinations, prevalence of relevant diseases, and academic status. For group B, sensitivity, specificity and area under receiver operating characteristic curve of the model in detecting centres with a <70% appropriateness rate were 54%, 93% and 0.72, respectively. CONCLUSIONS: A simple predictive rule, based on rate of patients referred by GPs, rate of urgent examinations, prevalence of relevant diseases and academic status, identified a small subset of centres characterised by a high rate of inappropriateness. These centres may be presumed to obtain the largest benefit from targeted educational programs. PMID- 20308028 TI - Elective cross-over transfer of the foot: case report. AB - The case of a patient with sequels of a right Syme amputation and a left replanted upper tibial amputation was treated with elective cross-transfer of the left foot and ankle to the right distal tibial stump, and the left below-knee (BK) stump was resurfaced with a latissimus dorsi free flap. The patient regained independent walking capacity with a left BK prosthesis at 8 months postoperatively. PMID- 20308029 TI - Genetic polymorphisms in the UDP-glucuronosyltransferase 1A1 (UGT1A1) gene and prostate cancer risk in Caucasian men. AB - BACKGROUND: Catechol-estrogen metabolites can induce carcinogenesis by acting as endogenous tumor initiators. Glucuronidation, mediated by the UDP glucuronosyltransferase 1A1 (UGT1A1) enzyme, is a main metabolic pathway of estrogen detoxification in steroid target tissues, such as the prostate. The aim of our study was to investigate the possible correlation between UGT1A1 promoter gene polymorphisms and prostate cancer risk. PATIENTS AND METHODS: 129 patients with prostate cancer and 260 healthy controls were included in our study. A(TA)TAA promoter polymorphism of UGT1A1 gene was studied using the Fragment Analysis Software of an automated DNA sequencer and three genotypes (homozygous 7/7, heterozygous 6/7 and normal homozygous 6/6) were identified. RESULTS: No significant differences were observed between the cancer group and controls regarding the genotyping distribution of the three UGT1A1 promoter genotypes (P>0.05). Also, no association was found between overall disease risk and the presence of the polymorphic homozygous genotype (TA(7)/TA(7) vs TA(6)/TA(7)+TA(6)/TA(6)) (P=0.18). In addition, no association was revealed between UGT1A1 genotype distribution and Gleason score (P=0.55). CONCLUSION: Our data suggest that the TA repeat polymorphism of UGT1A1 gene does not seem to alter prostate cancer risk susceptibility in Caucasian men. PMID- 20308030 TI - Associations between glutathione S-transferase pi Ile105Val and glyoxylate aminotransferase Pro11Leu and Ile340Met polymorphisms and early-onset oxaliplatin induced neuropathy. AB - PURPOSE: Although the risk of oxaliplatin-induced neuropathy depends on cumulative oxaliplatin dose, susceptibility to this adverse event differs greatly among patients. In this study, we investigated the associations between oxaliplatin-induced neuropathy and the following polymorphisms: glutathione S transferase pi (GSTP1) Ile(105)Val, and glyoxylate aminotransferase (AGXT) Pro(11)Leu and AGXT Ile(340)Met. EXPERIMENTAL DESIGN: Eighty-two Japanese patients with histologically confirmed colorectal cancer who received at least six cycles of the modified FOLFOX6 (m-FOLFOX6) regimen were enrolled. To minimize differences in cumulative oxaliplatin dose between patients, oxaliplatin-induced neuropathy was evaluated using an oxaliplatin-specific scale during the 2-week period after completion of the sixth cycle of treatment. RESULTS: Forty-four patients developed grade 2/3 oxaliplatin-induced neuropathy. There were more patients carrying at least one GSTP1(105)Val allele among the group with grade 2/3 neuropathy (18/44, 41%) than among the group with grade 1 neuropathy (9/38, 24%), although the difference was not statistically significant (P=0.098). There were similar numbers of patients carrying at least one AGXT(105)Met allele in the grade 2/3 neuropathy (7/44, 16%) and grade 1 neuropathy groups (5/38, 13%; P=0.725). The AGXT(11)Leu allele was not found in any of our patients or controls. CONCLUSIONS: We found no significant association between oxaliplatin induced neuropathy and the GSTP1 Ile(105)Val and AGXT Ile(340)Met polymorphisms. Given that no AGXT(11)Leu allele was found among our study population (n=177), evaluating this polymorphism in Japanese patients in future studies is likely to be uninformative. PMID- 20308031 TI - Functional polymorphisms to modulate luminal lipid exposure and risk of colorectal cancer. AB - PURPOSE: Fat absorption may play a crucial role in colorectal carcinogenesis by determining intra-colonic exposure to potentially carcinogenic lipid metabolites. METHODS: We conducted a population-based case-control study that included 1163 cases and 1501 controls to examine whether individuals who carry genetic variants associated with lower lipid absorption have a higher risk of colorectal cancer. Using Taqman assay, we determined FABP2 alanine (A)/threonine (T) polymorphism at codon 54 in exon-2 and APOE isoforms. Multivariable odds ratios (OR) and 95% confidence intervals (CI) were calculated by unconditional logistic regression models, assuming FABP2 A54 and APO non-E4 as high risk alleles. RESULTS: We found no associations with either of the polymorphisms. The OR associated with FABP2 A54 homozygotes compared with the others was 1.01 (95% CI; 0.86-1.45) and that for non-ApoE4 carriers compared with carries was 0.95 (95% CI; 0.80-1.13). However, there was a statistically significant negative interaction between total fat intake and FABP2 AA genotypes (p=0.025), indicating that the risk of colorectal cancer associated with this polymorphism is higher in the subjects with lower fat intake. CONCLUSIONS: These results suggest that these SNPs may not be useful in predicting colorectal cancer risk in populations with high fat intake. PMID- 20308032 TI - Airborne endotoxin concentrations in homes burning biomass fuel. AB - BACKGROUND: About half of the world's population is exposed to smoke from burning biomass fuels at home. The high airborne particulate levels in these homes and the health burden of exposure to this smoke are well described. Burning unprocessed biological material such as wood and dried animal dung may also produce high indoor endotoxin concentrations. OBJECTIVE: In this study we measured airborne endotoxin levels in homes burning different biomass fuels. METHODS: Air sampling was carried out in homes burning wood or dried animal dung in Nepal (n = 31) and wood, charcoal, or crop residues in Malawi (n = 38). Filters were analyzed for endotoxin content expressed as airborne endotoxin concentration and endotoxin per mass of airborne particulate. RESULTS: Airborne endotoxin concentrations were high. Averaged over 24 hr in Malawian homes, median concentrations of total inhalable endotoxin were 24 endotoxin units (EU)/m(3) in charcoal-burning homes and 40 EU/m(3) in wood-burning homes. Short cooking-time samples collected in Nepal produced median values of 43 EU/m(3) in wood-burning homes and 365 EU/m(3) in dung-burning homes, suggesting increasing endotoxin levels with decreasing energy levels in unprocessed solid fuels. CONCLUSIONS: Airborne endotoxin concentrations in homes burning biomass fuels are orders of magnitude higher than those found in homes in developed countries where endotoxin exposure has been linked to respiratory illness in children. There is a need for work to identify the determinants of these high concentrations, interventions to reduce exposure, and health studies to examine the effects of these sustained, near-occupational levels of exposure experienced from early life. PMID- 20308033 TI - Investigation of relationships between urinary biomarkers of phytoestrogens, phthalates, and phenols and pubertal stages in girls. AB - BACKGROUND: Hormonally active environmental agents may alter the course of pubertal development in girls, which is controlled by steroids and gonadotropins. OBJECTIVES: We investigated associations of concurrent exposures from three chemical classes (phenols, phthalates, and phytoestrogens) with pubertal stages in a multiethnic longitudinal study of 1,151 girls from New York City, New York, greater Cincinnati, Ohio, and northern California who were 6-8 years of age at enrollment (2004-2007). METHODS: We measured urinary exposure biomarkers at visit 1 and examined associations with breast and pubic hair development (present or absent, assessed 1 year later) using multivariate adjusted prevalence ratios (PR) and 95% confidence intervals (CIs). Modification of biomarker associations by age specific body mass index percentile (BMI%) was investigated, because adipose tissue is a source of peripubertal hormones. RESULTS: Breast development was present in 30% of girls, and 22% had pubic hair. High-molecular-weight phthalate (high MWP) metabolites were weakly associated with pubic hair development [adjusted PR, 0.94 (95% CI, 0.88-1.00), fifth vs. first quintile]. Small inverse associations were seen for daidzein with breast stage and for triclosan and high MWP with pubic hair stage; a positive trend was observed for low-molecular-weight phthalate biomarkers with breast and pubic hair development. Enterolactone attenuated BMI associations with breast development. In the first enterolactone quintile, for the association of high BMI with any development, the PR was 1.34 (95% CI, 1.23-1.45 vs. low BMI). There was no BMI association in the fifth, highest quintile of enterolactone. CONCLUSIONS: Weak hormonally active xenobiotic agents investigated in this study had small associations with pubertal development, mainly among those agents detected at highest concentrations. PMID- 20308034 TI - Exposure science: a view of the past and milestones for the future. AB - BACKGROUND: The study of human exposure to environmental toxicants has evolved as a scientific field over the past 30 years. OBJECTIVES: This review provides a historical perspective on the growth of exposure science as a field, with some emphasis on the results from initial observational studies in obtaining information needed for generating hypotheses on significant human contact with environmental agents, testing the performance of models, and reducing exposures to protect public health. DISCUSSION: Advances in activity pattern and behavioral research that established a suite of variables needed to accurately define contact and factors that influence contact are also discussed. The identification and characterization of these factors have played a pivotal role in the growth of the field and in developing exposure reduction strategies. Answers to two key questions on the relevance and fundamental value of exposure science to the fields of environmental health and risk management are presented as a path forward: a) What does one do with such exposure information? b) What roles does exposure science play in situations beyond observational analyses and interpretation? CONCLUSIONS: The discussion identifies the need for more focused use of observational studies of exposure for epidemiologic analyses. Further, the introduction and use of new tools and approaches for hypothesis testing that can improve the use of exposure science in prevention research for risk management is needed to affect the source-to-effect continuum. A major restructuring of the field is not required to achieve innovation. However, additional resources for training and education are required to ensure that the potential for exposure science to play a central role in reducing and preventing excess risk within environmental/occupational health is achieved. PMID- 20308035 TI - Common genetic variation, residential proximity to traffic exposure, and left ventricular mass: the multi-ethnic study of atherosclerosis. AB - BACKGROUND: Elevated left ventricular mass (LVM) is a strong predictor of negative cardiovascular outcomes, including heart failure, stroke, and sudden cardiac death. A relationship between close (< 50 m compared with > 150 m) residential proximity to major roadways and higher LVM has previously been described, but the mechanistic pathways that are involved in this relationship are not known. Understanding genetic factors that influence susceptibility to these effects may provide insight into relevant mechanistic pathways. OBJECTIVE: We set out to determine whether genetic polymorphisms in genes affecting vascular and autonomic function, blood pressure, or inflammation influence the relationship between traffic proximity and LVM. METHODS: This was a cross sectional study of 1,376 genotyped participants in the Multi-Ethnic Study of Atherosclerosis, with cardiac magnetic resonance imaging performed between 2000 and 2002. The impact of tagged single-nucleotide polymorphisms (tagSNPs) and inferred haplotypes in 12 candidate genes (ACE, ADRB2, AGT, AGTR1, ALOX15, EDN1, GRK4, PTGS1, PTGS2, TLR4, VEGFA, and VEGFB) on the relationship between residential proximity to major roadways and LVM was analyzed using multiple linear regression, adjusting for multiple potential confounders. RESULTS: After accounting for multiple testing and comparing homozygotes, tagSNPs in the type 1 angiotensin II receptor (AGTR1, rs6801836) and arachidonate 15-lipoxygenase (ALOX15, rs2664593) genes were each significantly (q < 0.2) associated with a 9 10% difference in the association between residential proximity to major roadways and LVM. Participants with suboptimal blood pressure control demonstrated stronger interactions between AGTR1 and traffic proximity. CONCLUSIONS: Common polymorphisms in genes responsible for vascular function, inflammation, and oxidative stress appear to modify associations between proximity to major roadways and LVM. Further understanding of how genes modify effects of air pollution on CVD may help guide research efforts into specific mechanistic pathways. PMID- 20308036 TI - Low-level mercury can enhance procoagulant activity of erythrocytes: a new contributing factor for mercury-related thrombotic disease. AB - BACKGROUND: Associations between cardiovascular diseases and mercury have been frequently described, but underlying mechanisms are poorly understood. OBJECTIVES: We investigate the procoagulant activation of erythrocytes, an important contributor to thrombosis, by low-level mercury to explore the roles of erythrocytes in mercury-related cardiovascular diseases. METHODS: We used freshly isolated human erythrocytes and ex vivo and in vivo thrombosis models in rats to investigate mercury-induced procoagulant activity. RESULTS: Prolonged exposure to low-dose mercuric ion (Hg(2+); 0.25-5 microM for 1-48 hr) induced erythrocyte shape changes from discocytes to echinocytes to spherocytes, accompanied by microvesicle (MV) generation. These MVs and remnant erythrocytes expressed phosphatidylserine (PS), an important mediator of procoagulant activation. Hg(2+) inhibited flippase, an enzyme that recovers PS into the inner leaflet of the cell membrane, and activated scramblase, an enzyme that alters lipid asymmetry in the cell membrane. Consistent with these activity changes, Hg(2+) increased intracellular calcium and depleted ATP and protein thiol. A thiol supplement reversed Hg(2+)-induced MV generation and PS exposure and inhibited the increase in calcium ion (Ca(2+)) and depletion of ATP, indicating that free-thiol depletion was critical to Hg(2+)-mediated procoagulant activity. The procoagulant activity of Hg(2+)-treated erythrocytes was demonstrated by increased thrombin generation and endothelial cell adhesion. We further confirmed Hg(2+)-mediated procoagulant activation of erythrocytes in ex vivo and in vivo rat thrombosis models, where Hg(2+) treatment (0.5-2.5 mg/kg) increased PS exposure and thrombus formation significantly. CONCLUSION: This study demonstrated that mercury could provoke procoagulant activity in erythrocytes through protein-thiol depletion mediated PS exposure and MV generation, ultimately leading to enhanced thrombosis. PMID- 20308037 TI - Value of community pharmacy residency programs: college of pharmacy and practice site perspectives. AB - OBJECTIVES: To describe and compare perceptions of key informants representing U.S. colleges/schools of pharmacy and community pharmacy practice sites regarding (1) value associated with community pharmacy residency programs (CPRPs) and (2) barriers to offering CPRPs . DESIGN: Descriptive, non-experimental, cross sectional study. SETTING: United States, June 13, 2009, through July 13, 2009. PARTICIPANTS: 554 respondents to a Web-based survey. INTERVENTION: Key informants representing the following four organizational groups were surveyed: (1) colleges/schools of pharmacy participating in CPRPs, (2) colleges/schools of pharmacy not participating in CPRPs, (3) CPRP community pharmacy practice sites, and (4) non-CPRP community pharmacy practice sites. MAIN OUTCOME MEASURES: Value of CPRPs to participating pharmacies, value of CPRPs to participating colleges/schools of pharmacy, and barriers to offering CPRPs. RESULTS: Overall, 267 key informants from colleges/schools of pharmacy and 287 key informants from pharmacy practice sites responded to the survey (n = 554 total respondents). Of these, 334 responders provided data that were usable for analysis. The most important types of value to the respondents were altruistic in nature (e.g., pharmacy education development, pharmacy profession development, community engagement). However, barriers to offering CPRPs were more practical and included challenges related to accreditation and operational issues. Further, evidence indicated that (1) lack of leadership, (2) lack of revenue generated from such programs, and (3) the cost of reimbursement for residents may be fundamental, multidimensional barriers to implementing CPRPs. CONCLUSION: Guidelines for starting and continuing CPRPs, "industry norms" that would require CPRP training for certain types of employment, and creation of models for patient care revenue would help develop and position CPRPs in the future. PMID- 20308038 TI - Handwritten 'post-it' notes, questionnaire formats and response to a postal questionnaire survey. PMID- 20308039 TI - Skeletal muscle proteomics in livestock production. AB - Proteomics allows studying large numbers of proteins, including their post translational modifications. Proteomics has been, and still are, used in numerous studies on skeletal muscle. In this article, we focus on its use in the study of livestock muscle development and meat quality. Changes in protein profiles during myogenesis are described in cattle, pigs and fowl using comparative analyses across different ontogenetic stages. This approach allows a better understanding of the key stages of myogenesis and helps identifying processes that are similar or divergent between species. Genetic variability of muscle properties analysed by the study of hypertrophied cattle and sheep are discussed. Biological markers of meat quality, particularly tenderness in cattle, pigs and fowl are presented, including protein modifications during meat ageing in cattle, protein markers of PSE meat in turkeys and of post-mortem muscle metabolism in pigs. Finally, we discuss the interest of proteomics as a tool to understand better biochemical mechanisms underlying the effects of stress during the pre-slaughter period on meat quality traits. In conclusion, the study of proteomics in skeletal muscles allows generating large amounts of scientific knowledge that helps to improve our understanding of myogenesis and muscle growth and to control better meat quality. PMID- 20308040 TI - Self-adjustment of phosphate binder dose to meal phosphorus content improves management of hyperphosphataemia in children with chronic kidney disease. AB - BACKGROUND: Hyperphosphataemia in patients with chronic kidney disease (CKD) is associated with mineral and bone disorder and increased cardiovascular mortality. Despite phosphate binders (PB), nutrition counselling and dialysis therapy, the prevalence of hyperphosphataemia remains unacceptably high. It was hypothesized that an inadequate relation of PB dose to meal inorganic phosphorus (iP) content may be an important factor for failure of phosphate management. METHODS: The innovative 'Phosphate Education Program' (PEP) bases on patient empowerment to eye-estimate meal iP content by newly defined 'Phosphate Units' (PU; 1 PU per 100 mg phosphorus) and self-adjust PB dosage to dietary iP intake by an individually prescribed PB/PU ratio (PB pills per PU). In a prospective study, 16 children (aged 4-17 years) with CKD and their parents were trained with the PEP concept and followed up for 24 weeks for changes in serum electrolyte levels, dietary behaviour and PB dose. RESULTS: Within 6 weeks after PEP training, the percentage of children with serum phosphate (PO) >1.78 mmol/l dropped from 63% (10/16) to 31% (5/16). Mean serum PO level decreased from 1.94 +/- 0.23 at baseline to 1.68 +/- 0.30 (SD) mmol/l in Week 7-12 (P = 0.02) and to 1.78 +/- 0.36 (SD) mmol/l in Week 19-24 (P = 0.2), whereas serum calcium [2.66 +/- 0.3 vs 2.60 +/- 0.23 (SD) mmol/l in Weeks 7-12 (P = 0.45) and 2.66 +/- 0.23 (SD) mmol/l in Week 19-24 (P = 0.21)] and serum potassium [4.69 +/- 0.48 vs 4.58 +/- 0.68 (SD) mmol/l in Week 7 12 (P = 0.40) and 4.65 +/- 0.49 (SD) mmol/l in Week 19-24 (P = 0.73)] remained unchanged. The mean daily PB dose rose from 6.3 +/- 2.9 to 8.2 +/- 5.4 (SD) pills during observation period with an increased meal-to-meal variability (P = 0.04). Dietary iP intake was not affected by PEP concept. CONCLUSION: The empowerment of children with CKD and their parents to self-adjust PB dose to eye-estimated meal iP content significantly improved management of hyperphosphataemia without reducing dietary iP intake. PMID- 20308041 TI - Usefulness of exercise-stress echocardiography for risk stratification of true asymptomatic patients with aortic valve stenosis. AB - Aims Abnormal exercise test defined as the occurrence of exercise limiting symptoms, fall in blood pressure below baseline, or complex ventricular arrhythmias is useful to predict clinical events in asymptomatic patients with aortic stenosis (AS). The purpose of this study was to determine whether exercise stress echocardiography (ESE) adds any incremental prognostic value to resting echocardiography in patients with AS having a normal exercise response. Methods and results One hundred and eighty-six asymptomatic patients with at least moderate AS and preserved LV ejection fraction (>/=50%) were assessed by Doppler echocardiography at rest and during a maximum ramp semi-supine bicycle exercise test. Fifty-one (27%) patients had an abnormal exercise test and were excluded from the present analysis. Among the 135 patients with normal exercise test, 67 had an event (aortic valve replacement motivated by symptoms or cardiovascular death) at a mean follow-up of 20 +/- 14 months. The variables independently associated with events were: age >/=65 years [hazard ratio (HR) = 1.96; 95% confidence interval (CI): 1.15-3.47; P = 0.01], diabetes, (HR = 3.20; 95% CI: 1.33-6.87; P = 0.01), LV hypertrophy (HR = 1.96; 95% CI: 1.17-3.27; P = 0.01), resting mean gradient >35 mmHg (HR = 3.60; 95% CI: 2.11-6.37; P < 0.0001), and exercise-induced increase in mean gradient >20 mmHg (HR = 3.83; 95% CI: 2.16 6.67; P < 0.0001). Conclusion The exercise-induced increase in transvalvular gradient may be helpful to improve risk stratification in asymptomatic AS patients with normal exercise response. These results thus suggest that ESE may provide additional prognostic information over that obtained from standard exercise testing and resting echocardiography. PMID- 20308042 TI - Exercise echocardiography in aortic stenosis: one more piece in the puzzle. PMID- 20308043 TI - Warning about the poor prognosis of squamous cell carcinoma of the thyroid. PMID- 20308044 TI - Familial and sporadic breast cancers: differences in clinical, histopathological, and immunohistochemical features. AB - In the present study, the authors investigated the clinical, histopathological, and immunohistochemical features in familial breast cancer (FBC) patients and compared them with findings in sporadic breast cancers (SBCs); hormone receptor status was stratified by age. A total of 849 patients treated for breast cancer were included in the study. The patients were stratified into 2 groups: FBC, 160 patients (19%), and SBC, 689 patients (81%). FBC tumors differed from SBC tumors by earlier age of diagnosis and low content of progesterone receptor (PR). These characteristics should be of value in evaluating the possibility of mutation and in targeting mutation screening in such families. PR gene polymorphism leads to an increased risk of breast cancer because it determines inadequate control of estrogen receptor (ER)-driven proliferative function. ER+/PR- tumors more frequently showed HER2 (human epidermal growth factor receptor) overexpression and represent a distinct subset in FBC patients. The authors suggest that late onset FBCs need more intensive therapy and a more careful follow-up. PMID- 20308045 TI - Tintin in the ruptured crypt. PMID- 20308046 TI - Improved success rate of cardiac resynchronization therapy implant by employing an active fixation coronary sinus lead. AB - AIMS: Cardiac resynchronization therapy (CRT) is the standard treatment for heart failure with severe reduced left ventricular (LV) function and wide QRS complex. Coronary sinus (CS) lead implantation is challenging and accompanied by substantial dislocation rates. We evaluated the usage of an active fixation LV lead (Attain Starfix, Medtronic, MN, USA) with deployable lobes in challenging lead positions. METHODS AND RESULTS: Between September 2006 and August 2009, 678 CRT devices were implanted. In 82 patients (12%) (59 male, 70 +/- 10 years, 39 ICM, 41 DCM, 2 valvular CM, LVEF 28 +/- 9%, NYHA 3.0 +/- 0.4, QRS 169 +/- 29 ms), the Attain Starfix active fixation lead was used. The main reason was intra operative dislodgement of one (n = 47) or two (n = 5) passive fixation leads during implantation or revision procedure (n = 30). Active fixation lead implantation was overall successful with 90% (n = 74). Anatomical peculiarity was mostly an optimal lead position in otherwise unstable proximal parts of the target vein or a circumscripted areal of optimal threshold without phrenic nerve stimulation. At median follow-up of 99 days the threshold remained stable (1.2 +/ 0.8 vs. 1.0 +/- 0.5 V at 0.5 ms). Revisions due to instability in ectatic vein (n = 1) after 12 months and extractions (n = 2) because of device perforation/infection after 6/15 months were performed without complication. CONCLUSION: The Attain Starfix active fixation lead proved to be an important option in anatomically challenging, otherwise unstable positions often located in the proximal part of the target vein. Lead revisions or extractions as late as 15 months after implantation were feasible. PMID- 20308047 TI - Right- and left-hand performance on the Rey-Osterrieth Complex Figure: A preliminary study in non-clinical sample of right handed people. AB - Intermanual differences in performing the Rey-Osterrieth Complex Figure Test (ROCFT) were experimentally investigated. Undergraduate participants (n = 120; 60 men, 60 women) were randomly assigned to one of four groups based on the hand used in a copy trial and a recall test. Hand use had a minimal effect on performance in the copy trial. However, recall accuracy was lower when the non dominant left hand was used in the copy trial than when the dominant right hand was used, regardless of the hand used in the recall test. These findings are important from a clinical perspective, especially in cases in which patients use the non-dominant hand due to hemiplegia of the dominant hand when conducting the ROCFT. PMID- 20308048 TI - Nitrogen use efficiencies of spring barley grown under varying nitrogen conditions in the field and growth chamber. AB - BACKGROUND AND AIMS: Nitrogen-use efficiency (NUE) of cereals needs to be improved by nitrogen (N) management, traditional plant breeding methods and/or biotechnology, while maintaining or, optimally, increasing crop yields. The aims of this study were to compare spring-barley genotypes grown on different nitrogen levels in field and growth-chamber conditions to determine the effects on N uptake (NUpE) and N utilization efficiency (NUtE) and ultimately, NUE. METHODS: Morphological characteristics, seed yield and metabolite levels of 12 spring barley (Hordeum vulgare) genotypes were compared when grown at high and low nitrogen levels in field conditions during the 2007 and 2008 Canadian growing seasons, and in potted and hydroponic growth-chamber conditions. Genotypic NUpE, NUtE and NUE were calculated and compared between field and growth-chamber environments. KEY RESULTS: Growth chamber and field tests generally showed consistent NUE characteristics. In the field, Vivar, Excel and Ponoka, showed high NUE phenotypes across years and N levels. Vivar also had high NUE in growth chamber trials, showing NUE across complex to simplistic growth environments. With the high NUE genotypes grown at low N in the field, NUtE predominates over NUpE. N metabolism-associated amino acid levels were different between roots (elevated glutamine) and shoots (elevated glutamate and alanine) of hydroponically grown genotypes. In field trials, metabolite levels were different between Kasota grown at high N (elevated glutamine) and Kasota at low N plus Vivar at either N condition. CONCLUSIONS: Determining which trait(s) or gene(s) to target to improve barley NUE is important and can be facilitated using simplified growth approaches to help determine the NUE phenotype of various genotypes. The genotypes studied showed similar growth and NUE characteristics across field and growth-chamber tests demonstrating that simplified, low-variable growth environments can help pinpoint genetic targets for improving spring barley NUE. PMID- 20308049 TI - Silencing ataxin-3 mitigates degeneration in a rat model of Machado-Joseph disease: no role for wild-type ataxin-3? AB - Machado-Joseph disease or spinocerebellar ataxia type 3 (MJD/SCA3) is a fatal, autosomal dominant disorder caused by a cytosine-adenine-guanine expansion in the coding region of the MJD1 gene. RNA interference has potential as a therapeutic approach but raises the issue of the role of wild-type ataxin-3 (WT ATX3) in MJD and of whether the expression of the wild-type protein must be maintained. To address this issue, we both overexpressed and silenced WT ATX3 in a rat model of MJD. We showed that (i) overexpression of WT ATX3 did not protect against MJD pathology, (ii) knockdown of WT ATX3 did not aggravate MJD pathology and that (iii) non-allele-specific silencing of ataxin-3 strongly reduced neuropathology in a rat model of MJD. Our findings indicate that therapeutic strategies involving non-allele-specific silencing to treat MJD patients may be safe and effective. PMID- 20308050 TI - SOX10 structure-function analysis in the chicken neural tube reveals important insights into its role in human neurocristopathies. AB - The HMG-domain containing transcription factor Sox10 is essential for neural crest (NC) development and for oligodendrocyte differentiation. Heterozygous SOX10 mutations in humans lead to corresponding defects in several NC-derived lineages and to leukodystrophies. Disease phenotypes range from Waardenburg syndrome and Waardenburg-Hirschsprung disease to Peripheral demyelinating neuropathy, Central dysmyelination, Waardenburg syndrome and Hirschsprung disease (PCWH). The phenotypic variability can partly be explained by the action of modifier genes, but is also influenced by the mutation that leads to haploinsufficiency in some and to mutant SOX10 proteins with altered properties in other cases. Here, we used in ovo electroporation in the developing neural tube of chicken to determine which regions and properties of SOX10 are required for early NC development. We found a strict reliance on the DNA-binding activity and the presence of the C-terminal transactivation domain and a lesser influence of the dimerization function and a conserved domain in the center of the protein. Intriguingly, dominant-negative effects on early NC development were mostly observed for truncated SOX10 proteins whose production in patients is probably prevented by nonsense-mediated decay. In contrast, mutant SOX10 proteins that occur in patients were usually inactive. Any dominant negative activity which some of these mutants undoubtedly possess must, therefore, be restricted to single NC-derived cell lineages or oligodendrocytes at later times. This contributes to the phenotypic variability of human SOX10 mutations. PMID- 20308051 TI - Quality control for exposure assessment in epidemiological studies. AB - In the framework of an epidemiological study, dosemeters were used for the assessment of radio frequency electromagnetic field exposure. To check the correct dosemeter's performance in terms of consistency of recorded field values over the entire study period, a quality control strategy was developed. In this paper, the concept of quality control and its results is described. From the 20 dosemeters used, 19 were very stable and reproducible, with deviations of a maximum of +/-1 dB compared with their initial state. One device was found to be faulty and its measurement data had to be excluded from the analysis. As a result of continuous quality control procedures, the confidence in the measurements obtained during the field work was strengthened significantly. PMID- 20308052 TI - Study on the response of thermoluminescent dosemeters to synchrotron radiation: experimental method and Monte Carlo calculations. AB - In the present study, the energy dependence of response of some popular thermoluminescent dosemeters (TLDs) have been investigated such as LiF:Mg,Ti, LiF:Mg,Cu,P and CaSO(4):Dy to synchrotron radiation in the energy range of 10-34 keV. The study utilised experimental, Monte Carlo and analytical methods. The Monte Carlo calculations were based on the EGSnrc and FLUKA codes. The calculated energy response of all the TLDs using the EGSnrc and FLUKA codes shows excellent agreement with each other. The analytically calculated response shows good agreement with the Monte Carlo calculated response in the low-energy region. In the case of CaSO(4):Dy, the Monte Carlo-calculated energy response is smaller by a factor of 3 at all energies in comparison with the experimental response when polytetrafluoroethylene (PTFE) (75 % by wt) is included in the Monte Carlo calculations. When PTFE is ignored in the Monte Carlo calculations, the difference between the calculated and experimental response decreases (both responses are comparable >25 keV). For the LiF-based TLDs, the Monte Carlo-based response shows reasonable agreement with the experimental response. PMID- 20308053 TI - Animal models for Klinefelter's syndrome and their relevance for the clinic. AB - In mammals, the contribution of the Y chromosome is paramount for male sexual determination; however, the presence of a single functional X chromosome is also of importance. In contrast to females where X inactivation is seen; the X chromosome of the male stays active. When, due to meiotic non-disjunction events, males are born with a supernumerary X chromosome, the resulting 47, XXY karyotype is referred to as Klinefelter's syndrome. This frequent genetic condition is most commonly associated with infertility, hypogonadism, gynecomastia and cognitive impairments. The condition has also been associated with a reduced life expectancy, insulin resistance, dyslipidemia, increased body fat mass and reduced bone mineral content. In a variety of species, male animals with karyotypes resembling Klinefelter's syndrome arise and develop a subset of features similar to those seen in humans. The availability of these animals is driving efforts to experimentally address the pathophysiology of the condition. To date, two models, 41, XXY and 41, XX(Y)* (mutated Y chromosome) male mice, have been established which resemble aspects of the pathophysiology of Klinefelter's syndrome. Experiments performed in these models confirm that the presence of a supernumerary X chromosome causes germ cell loss, cognitive deficits, Leydig cell hyperplasia, and that their Sertoli cells are capable of supporting germ cells of normal karyotype. This review summarizes the generation and characterization of the animal models for Klinefelter's syndrome and suggests experimental strategies to improve our understanding of the mechanisms underlying the pathophysiology of Klinefelter's syndrome. PMID- 20308054 TI - Price deflation and the underground organ economy in the Philippines. AB - BACKGROUND: This is the first in-depth study of the illicit human organ trade in the Philippines. The question for analytical investigation is why the underground organ commerce thrives, despite meager support and compensation for commercial donors (or vendors). METHODS: Quantitative survey results were obtained from a probability sample of living Filipino kidney vendors (P = 0.95; alpha = 0.05). The kidney trade was studied because it has the highest level of demand among all tradeable human organs in the Philippines and globally. RESULTS: The study finds that deflated vendor compensation, lower than global kidney purchase prices, and relative stability in kidney supply obtain from a combination of the socio economic characteristics of Filipino vendors and the asymmetric information available to them. The high degree of ambiguity and continuity between legitimate organ donations and underground buy-and-sell operations poses major challenges to effective regulation and law enforcement on the part of the Philippine government. CONCLUSIONS: Any reform effort will need to effectively address the fine distinction between two different but overlapping organ procurement markets, and brokered trading, with minimal transaction costs, based on asymmetric information. Policy lessons and insights from the Philippine experience that are transferable to other countries, particularly in the developing world, are noted in this study. PMID- 20308055 TI - Prevalence of the use of self-tests by adults in the United Kingdom: a questionnaire survey. AB - BACKGROUND: Self-tests that people can do without a health professional are widely available, but there is little information about how many people have used one. Our aim was to describe the prevalence of use. METHODS: An initial questionnaire, sent to 8048 adults registered with six general practices in North Birmingham and Warwickshire and Worcestershire, asked whether the person had self tested. A second questionnaire validated the use for people from the final four practices by asking how each self-test had been obtained and why it had been used. RESULTS: The age-standardised prevalence of confirmed use for any self-test other than for pregnancy or high blood pressure was 47 (95% confidence interval (CI): 37-57) per 1000 women and 22 (95% CI: 14-30) per 1000 men. If everyone who initially reported use but did not return an eligible second questionnaire had the same rates of confirmed use as eligible responders, this would increase to 95 (95% CI: 81-110) per 1000 women and 55 (95% CI: 41-68) per 1000 men. CONCLUSION: An appreciable minority of the population have self-tested for medical conditions. PMID- 20308056 TI - Mast cell-derived prostaglandin D2 controls hyaluronan synthesis in human orbital fibroblasts via DP1 activation: implications for thyroid eye disease. AB - Thyroid eye disease (TED) is a debilitating disorder characterized by the accumulation of adipocytes and hyaluronan (HA). Production of HA by fibroblasts leads to remarkable increases in tissue volume and to the anterior displacement of the eyes. Prostaglandin D(2) (PGD(2)), mainly produced by mast cells, promotes orbital fibroblast adipogenesis. The mechanism by which PGD(2) influences orbital fibroblasts and their synthesis of HA is poorly understood. We report here that mast cell-derived PGD(2) is a key factor that promotes HA biosynthesis by orbital fibroblasts. Primary orbital fibroblasts from TED patients were isolated and used to test the effects of PGD(2), prostaglandin J(2), as well as prostaglandin D receptor (DP) agonists and antagonists on HA synthesis. The expression of HA synthase (HAS), hyaluronidase, DP1, and DP2 mRNA levels was assessed by PCR. Small interfering RNAs against HAS1 or HAS2 were used to assess the importance of HAS isoforms on HA production. Treatment of human orbital fibroblasts with PGD(2) and PGJ(2) increased HA synthesis and HAS mRNA. HAS2 was the dominant isoform responsible for HA production by PGD(2). The effect of PGD(2) on HA production was mimicked by the selective DP1 agonist BW245C. The DP1 antagonist MK-0524 completely blocked PGD(2)-induced HA synthesis. Human mast cells (HMC-1) produced PGD(2). Co-culture of HMC-1 cells with orbital fibroblasts induced HA production and inhibition of mast cell-derived PGD(2) prevented HA synthesis. Mast cell derived PGD(2) increased HA production via activation of DP1. Selectively targeting the production of PGD(2) and/or activation of DP1 may prevent pathological changes associated with TED. PMID- 20308057 TI - RasGRP1 is essential for ras activation by the tumor promoter 12-O tetradecanoylphorbol-13-acetate in epidermal keratinocytes. AB - RasGRP1 is a guanine nucleotide exchange factor for Ras that binds with high affinity to diacylglycerol analogs like the phorbol esters. Recently, we demonstrated a role for RasGRP1 in skin carcinogenesis and suggested its participation in the action of tumor-promoting phorbol esters like 12-O tetradecanoylphorbol-13-acetate (TPA) on Ras pathways in epidermal cells. Given the importance of Ras in carcinogenesis, we sought to discern whether RasGRP1 was a critical pathway in Ras activation, using a RasGRP1 knockout (KO) mouse model to examine the response of keratinocytes to TPA. In contrast to the effect seen in wild type keratinocytes, Ras(GTP) levels were barely detected in RasGRP1 KO cells even after 60 min of exposure to phorbol esters. The lack of response was rescued by enforced expression of RasGRP1. Furthermore, small hairpin RNA-induced silencing of RasGRP1 abrogated the effect of TPA on Ras. Analysis of Ras isoforms showed that both H-Ras and N-Ras depended on RasGRP1 for activation by TPA, whereas activation of K-Ras could not be detected. Although RasGRP1 was dispensable for ERK activation in response to TPA, JNK activation was reduced in the KO keratinocytes. Notably, TPA-induced phosphorylation of JNK2, but not JNK1, was reduced by RasGRP1 depletion. These data identify RasGRP1 as a critical molecule in the activation of Ras by TPA in primary mouse keratinocytes and suggest JNK2 as one of the relevant downstream targets. Given the role of TPA as a skin tumor promoter, our findings provide additional support for a role for RasGRP1 in skin carcinogenesis. PMID- 20308058 TI - Hsc70 rapidly engages tau after microtubule destabilization. AB - The microtubule-associated protein Tau plays a crucial role in regulating the dynamic stability of microtubules during neuronal development and synaptic transmission. In a group of neurodegenerative diseases, such as Alzheimer disease and other tauopathies, conformational changes in Tau are associated with the initial stages of disease pathology. Folding of Tau into the MC1 conformation, where the amino acids at residues 7-9 interact with residues 312-342, is one of the earliest pathological alterations of Tau in Alzheimer disease. The mechanism of this conformational change in Tau and the subsequent effect on function and association to microtubules is largely unknown. Recent work by our group and others suggests that members of the Hsp70 family play a significant role in Tau regulation. Our new findings suggest that heat shock cognate (Hsc) 70 facilitates Tau-mediated microtubule polymerization. The association of Hsc70 with Tau was rapidly enhanced following treatment with microtubule-destabilizing agents. The fate of Tau released from the microtubule was found to be dependent on ATPase activity of Hsc70. Microtubule destabilization also rapidly increased the MC1 folded conformation of Tau. An in vitro assay suggests that Hsc70 facilitates formation of MC1 Tau. However, in a hyperphosphorylating environment, the formation of MC1 was abrogated, but Hsc70 binding to Tau was enhanced. Thus, under normal circumstances, MC1 formation may be a protective conformation facilitated by Hsc70. However, in a diseased environment, Hsc70 may preserve Tau in a more unstructured state, perhaps facilitating its pathogenicity. PMID- 20308059 TI - Midkine and pleiotrophin have bactericidal properties: preserved antibacterial activity in a family of heparin-binding growth factors during evolution. AB - Antibacterial peptides of the innate immune system combat pathogenic microbes, but often have additional roles in promoting inflammation and as growth factors during tissue repair. Midkine (MK) and pleiotrophin (PTN) are the only two members of a family of heparin-binding growth factors. They show restricted expression during embryogenesis and are up-regulated in neoplasia. In addition, MK shows constitutive and inflammation-dependent expression in some non transformed tissues of the adult. In the present study, we show that both MK and PTN display strong antibacterial activity, present at physiological salt concentrations. Electron microscopy of bacteria and experiments using artificial lipid bilayers suggest that MK and PTN exert their antibacterial action via a membrane disruption mechanism. The predicted structure of PTN, employing the previously solved MK structure as a template, indicates that both molecules consist of two domains, each containing three antiparallel beta-sheets. The antibacterial activity was mapped to the unordered C-terminal tails of both molecules and the last beta-sheets of the N-terminals. Analysis of the highly conserved MK and PTN orthologues from the amphibian Xenopus laevis and the fish Danio rerio suggests that they also harbor antibacterial activity in the corresponding domains. In support of an evolutionary conserved function it was found that the more distant orthologue, insect Miple2 from Drosophila melanogaster, also displays strong antibacterial activity. Taken together, the findings suggest that MK and PTN, in addition to their earlier described activities, may have previously unrealized important roles as innate antibiotics. PMID- 20308060 TI - The PX-RICS-14-3-3zeta/theta complex couples N-cadherin-beta-catenin with dynein dynactin to mediate its export from the endoplasmic reticulum. AB - We have recently shown that beta-catenin-facilitated export of cadherins from the endoplasmic reticulum requires PX-RICS, a beta-catenin-interacting GTPase activating protein for Cdc42. Here we show that PX-RICS interacts with isoforms of 14-3-3 and couples the N-cadherin-beta-catenin complex to the microtubule based molecular motor dynein-dynactin. Similar to knockdown of PX-RICS, knockdown of either 14-3-3zeta or - resulted in the disappearance of N-cadherin and beta catenin from the cell-cell boundaries. Furthermore, we found that PX-RICS and 14 3-3zeta/ are present in a large multiprotein complex that contains dynein dynactin components as well as N-cadherin and beta-catenin. Both RNAi- and dynamitin-mediated inhibition of dynein-dynactin function also led to the absence of N-cadherin and beta-catenin at the cell-cell contact sites. Our results suggest that the PX-RICS-14-3-3zeta/ complex links the N-cadherin-beta-catenin cargo with the dynein-dynactin motor and thereby mediates its endoplasmic reticulum export. PMID- 20308061 TI - Two distinct regions of latency-associated peptide coordinate stability of the latent transforming growth factor-beta1 complex. AB - Transforming growth factor-beta1 (TGF-beta1) is secreted as part of an inactive complex consisting of the mature dimer, the TGF-beta1 propeptide (latency associated peptide (LAP)), and latent TGF-beta-binding proteins. Using in vitro mutagenesis, we identified the regions of LAP that govern the cooperative assembly and stability of the latent TGF-beta1 complex. Initially, hydrophobic LAP residues (Ile(53), Leu(54), Leu(57), and Leu(59)), which form a contiguous epitope on one surface of an amphipathic alpha-helix, interact with mature TGF beta1 to form the small latent complex. TGF-beta1 binding is predicted to alter LAP conformation, exposing ionic residues (Arg(45), Arg(50), Lys(56), and Arg(58)) on the other side of the alpha-helix, which form the binding site for latent TGF-beta-binding proteins. The stability of the resultant large latent complex is dependent upon covalent dimerization of LAP, which is facilitated by key residues (Phe(198), Asp(199), Val(200), Leu(208), Phe(217), and Leu(219)) at the dimer interface. Significantly, genetic mutations in LAP (e.g. R218H) that cause the rare bone disorder Camurati-Engelmann disease disrupted dimerization and reduced the stability of the latent TGF-beta1 complex. PMID- 20308062 TI - Functional characterization of Wiskott-Aldrich syndrome protein and scar homolog (WASH), a bi-modular nucleation-promoting factor able to interact with biogenesis of lysosome-related organelle subunit 2 (BLOS2) and gamma-tubulin. AB - The Arp2/3 complex is essential for actin filament nucleation in a variety of cellular processes. The activation of the Arp2/3 complex is mediated by nucleation-promoting factors, such as the Wiskott-Aldrich syndrome family proteins, which share a WCA (WH2 domain, central region, acidic region) catalytic module at the C-terminal region, required for Arp2/3 activation, but diverge at the N-terminal region, required for binding to specific activators. Here, we report the characterization of WASH, a new member of the WAS family that has nucleation-promoting factor activity and recently has been demonstrated to play a role in endosomal sorting. We found that overexpression of the WASH-WCA domain induced disruption of the actin cytoskeleton, whereas overexpression of full length WASH in mammalian cells did not affect stress fiber organization. Furthermore, our analysis has revealed that nerve growth factor treatment of PC12 cells overexpressing full-length WASH leads to disruption of the actin cytoskeleton. We have also found that WASH interacts through its N-terminal region with BLOS2, a centrosomal protein belonging to the BLOC-1 complex that functions as a scaffolding factor in the biogenesis of lysosome-related organelles. In addition to BLOS2, WASH also interacts with centrosomal gamma tubulin and with pallidin, an additional component of the BLOC-1 complex. Collectively, our data propose that WASH is a bimodular protein in which the C terminus is involved in Arp2/3-mediated actin nucleation, whereas the N-terminal portion is required for its regulation and localization in the cells. Moreover, our data suggest that WASH is also a component of the BLOC-1 complex that is associated with the centrosomes. PMID- 20308063 TI - Ion-dependent polymerization differences between mammalian beta- and gamma nonmuscle actin isoforms. AB - beta- and gamma-nonmuscle actins differ by 4 amino acids at or near the N terminus and distant from polymerization interfaces. beta-Actin contains an Asp(1)-Asp(2)-Asp(3) and Val(10) whereas gamma-actin has a Glu(1)-Glu(2)-Glu(3) and Ile(10). Despite these small changes, conserved across mammals, fish, and birds, their differential localization in the same cell suggests they may play different roles reflecting differences in their biochemical properties. To test this hypothesis, we established a baculovirus-driven expression system for producing these actins in isoform-pure populations although contaminated with 20 25% insect actin. Surprisingly, Ca-gamma-actin exhibits a slower monomeric nucleotide exchange rate, a much longer nucleation phase, and a somewhat slower elongation rate than beta-actin. In the Mg-form, this difference between the two is much smaller. Ca-gamma-actin depolymerizes half as fast as does beta-actin. Mixing experiments with Ca-actins reveal the two will readily co-polymerize. In the Ca-form, phosphate release from polymerizing beta-actin occurs much more rapidly and extensively than polymerization, whereas phosphate release lags behind polymerization with gamma-actin. Phosphate release during treadmilling is twice as fast with beta- as with gamma-actin. With Mg-actin in the initial stages, phosphate release for both actins correlates much more closely with polymerization. Calcium bound in the high affinity binding site of gamma-actin may cause a selective energy barrier relative to beta-actin that retards the equilibration between G- and F-monomer conformations resulting in a slower polymerizing actin with greater filament stability. This difference may be particularly important in sites such as the gamma-actin-rich cochlear hair cell stereocilium where local mm calcium concentrations may exist. PMID- 20308064 TI - Involvement of heterogeneous ribonucleoprotein F in the regulation of cell proliferation via the mammalian target of rapamycin/S6 kinase 2 pathway. AB - The S6 kinases (S6Ks) have been linked to a number of cellular processes, including translation, insulin metabolism, cell survival, and RNA splicing. Signaling via the phosphotidylinositol 3-kinase and mammalian target of rapamycin (mTOR) pathways is critical in regulating the activity and subcellular localization of S6Ks. To date, nuclear functions of both S6K isoforms, S6K1 and S6K2, are not well understood. To better understand S6K nuclear roles, we employed affinity purification of S6Ks from nuclear preparations followed by mass spectrometry analysis for the identification of novel binding partners. In this study, we report that in contrast to S6K1, the S6K2 isoform specifically associates with a number of RNA-binding proteins, including heterogeneous ribonucleoproteins (hnRNPs). We focused on studying the mechanism and physiological relevance of the S6K2 interaction with hnRNP F/H. Interestingly, the S6K2-hnRNP F/H interaction was not affected by mitogenic stimulation, whereas mTOR binding to hnRNP F/H was induced by serum stimulation. In addition, we define a new role of hnRNP F in driving cell proliferation, which could be partially attenuated by rapamycin treatment. S6K2-driven cell proliferation, on the other hand, could be blocked by small interfering RNA-mediated down regulation of hnRNP F. These results demonstrate that the specific interaction between mTOR and S6K2 with hnRNPs is implicated in the regulation of cell proliferation. PMID- 20308065 TI - TPPP/p25 promotes tubulin acetylation by inhibiting histone deacetylase 6. AB - TPPP/p25 (tubulin polymerization-promoting protein/p25) is an unstructured protein that induces microtubule polymerization in vitro and is aligned along the microtubule network in transfected mammalian cells. In normal human brain, TPPP/p25 is expressed predominantly in oligodendrocytes, where its expression is proved to be crucial for their differentiation process. Here we demonstrated that the expression of TPPP/p25 in HeLa cells, in doxycycline-inducible CHO10 cells, and in the oligodendrocyte CG-4 cells promoted the acetylation of alpha-tubulin at residue Lys-40, whereas its down-regulation by specific small interfering RNA in CG-4 cells or by the withdrawal of doxycycline from CHO10 cells decreased the acetylation level of alpha-tubulin. Our results indicate that TPPP/p25 binds to HDAC6 (histone deacetylase 6), an enzyme responsible for tubulin deacetylation. Moreover, we demonstrated that the direct interaction of these two proteins resulted in the inhibition of the deacetylase activity of HDAC6. The measurement of HDAC6 activity showed that TPPP/p25 is able to induce almost complete (90%) inhibition at 3 microM concentration. In addition, treatment of the cells with nocodazole, vinblastine, or cold exposure revealed that microtubule acetylation induced by trichostatin A, a well known HDAC6 inhibitor, does not cause microtubule stabilization. In contrast, the microtubule bundling activity of TPPP/p25 was able to protect the microtubules from depolymerization. Finally, we demonstrated that, similarly to other HDAC6 inhibitors, TPPP/p25 influences the microtubule dynamics by decreasing the growth velocity of the microtubule plus ends and also affects cell motility as demonstrated by time lapse video experiments. Thus, we suggest that TPPP/p25 is a multiple effector of the microtubule organization. PMID- 20308066 TI - LVIS553 transcriptional regulator specifically recognizes novobiocin as an effector molecule. AB - In this study we aimed to identify small molecules with high affinity involved in the allosteric regulation of LVIS553, a MarR member from Lactobacillus brevis ATCC367. Using high throughput screening, novobiocin was found to specifically bind LVIS553 with a K(D) = 33.8 +/- 2.9 microM consistent with a biologically relevant ligand. Structure guided site-directed mutagenesis identified Lys(9) as a key residue in novobiocin recognition. The results found in vitro were correlated in vivo. An increased tolerance to the antibiotic was observed when LVIS553 and the downstream putative transport protein LVIS552 were either expressed in a low copy plasmid in L. brevis or as a single copy chromosomal insertion in Bacillus subtilis. We provide evidence that LVIS553 is involved in the specific regulation of a new mechanism of tolerance to novobiocin. PMID- 20308067 TI - Conserved 3'-untranslated region sequences direct subcellular localization of chaperone protein mRNAs in neurons. AB - mRNA localization provides polarized cells with a locally renewable source of proteins. In neurons, mRNA translation can occur at millimeters to centimeters from the cell body, giving the dendritic and axonal processes a means to autonomously respond to their environment. Despite that hundreds of mRNAs have been detected in neuronal processes, there are no reliable means to predict mRNA localization elements. Here, we have asked what RNA elements are needed for localization of transcripts encoding endoplasmic reticulum chaperone proteins in neurons. The 3'-untranslated regions (UTRs) of calreticulin and Grp78/BiP mRNAs show no homology to one another, but each shows extensive regions of high sequence identity to their 3'UTRs in mammalian orthologs. These conserved regions are sufficient for subcellular localization of reporter mRNAs in neurons. The 3'UTR of calreticulin has two conserved regions, and either of these is sufficient for axonal and dendritic targeting. However, only nucleotides 1315 1412 show ligand responsiveness to neurotrophin 3 (NT3) and myelin-associated glycoprotein (MAG). This NT3- and MAG-dependent axonal mRNA transport requires activation of JNK, both for calreticulin mRNA and for other mRNAs whose axonal levels are commonly regulated by NT3 and MAG. PMID- 20308068 TI - Inducible dimerization and inducible cleavage reveal a requirement for both processes in caspase-8 activation. AB - Caspase-8 is a cysteine protease activated by membrane-bound receptors at the cytosolic face of the cell membrane, initiating the extrinsic pathway of apoptosis. Caspase-8 activation relies on recruitment of inactive monomeric zymogens to activated receptor complexes, where they produce a fully active enzyme composed of two catalytic domains. Although in vitro studies using drug mediated affinity systems or kosmotropic salts to drive dimerization have indicated that uncleaved caspase-8 can be readily activated by dimerization alone, in vivo results using mouse models have reached the opposite conclusion. Furthermore, in addition to interdomain autoprocessing, caspase-8 can be cleaved by activated executioner caspases, and reports of whether this cleavage event can lead to activation of caspase-8 have been conflicting. Here, we address these questions by carrying out studies of the activation characteristics of caspase-8 mutants bearing prohibitive mutations at the interdomain cleavage sites both in vitro and in cell lines lacking endogenous caspase-8, and we find that elimination of these cleavage sites precludes caspase-8 activation by prodomain driven dimerization. We then further explore the consequences of interdomain cleavage of caspase-8 by adapting the tobacco etch virus protease to create a system in which both the cleavage and the dimerization of caspase-8 can be independently controlled in living cells. We find that unlike the executioner caspases, which are readily activated by interdomain cleavage alone, neither dimerization nor cleavage of caspase-8 alone is sufficient to activate caspase-8 or induce apoptosis and that only the coordinated dimerization and cleavage of the zymogen produce efficient activation in vitro and apoptosis in cellular systems. PMID- 20308069 TI - Topologically random insertion of EmrE supports a pathway for evolution of inverted repeats in ion-coupled transporters. AB - Inverted repeats in ion-coupled transporters have evolved independently in many unrelated families. It has been suggested that this inverted symmetry is an essential element of the mechanism that allows for the conformational transitions in transporters. We show here that small multidrug transporters offer a model for the evolution of such repeats. This family includes both homodimers and closely related heterodimers. In the former, the topology determinants, evidently identical in each protomer, are weak, and we show that for EmrE, an homodimer from Escherichia coli, the insertion into the membrane is random, and dimers are functional whether they insert into the cytoplasmic membrane with the N- and C terminal domains facing the inside or the outside of the cell. Also, mutants designed to insert with biased topology are functional regardless of the topology. In the case of EbrAB, a heterodimer homologue supposed to interact antiparallel, we show that one of the subunits, EbrB, can also function as a homodimer, most likely in a parallel mode. In addition, the EmrE homodimer can be forced to an antiparallel topology by fusion of an additional transmembrane segment. The simplicity of the mechanism of coupling ion and substrate transport and the few requirements for substrate recognition provide the robustness necessary to tolerate such a unique and unprecedented ambiguity in the interaction of the subunits and in the dimer topology relative to the membrane. The results suggest that the small multidrug transporters are at an evolutionary junction and provide a model for the evolution of structure of transport proteins. PMID- 20308070 TI - An improved ivermectin-activated chloride channel receptor for inhibiting electrical activity in defined neuronal populations. AB - The ability to silence the electrical activity of defined neuronal populations in vivo is dramatically advancing our understanding of brain function. This technology may eventually be useful clinically for treating a variety of neuropathological disorders caused by excessive neuronal activity. Several neuronal silencing methods have been developed, with the bacterial light activated halorhodopsin and the invertebrate allatostatin-activated G protein coupled receptor proving the most successful to date. However, both techniques may be difficult to implement clinically due to their requirement for surgically implanted stimulus delivery methods and their use of nonhuman receptors. A third silencing method, an invertebrate glutamate-gated chloride channel receptor (GluClR) activated by ivermectin, solves the stimulus delivery problem as ivermectin is a safe, well tolerated drug that reaches the brain following systemic administration. However, the limitations of this method include poor functional expression, possibly due to the requirement to coexpress two different subunits in individual neurons, and the nonhuman origin of GluClR. Here, we describe the development of a modified human alpha1 glycine receptor as an improved ivermectin-gated silencing receptor. The crucial development was the identification of a mutation, A288G, which increased ivermectin sensitivity almost 100-fold, rendering it similar to that of GluClR. Glycine sensitivity was eliminated via the F207A mutation. Its large unitary conductance, homomeric expression, and human origin may render the F207A/A288G alpha1 glycine receptor an improved silencing receptor for neuroscientific and clinical purposes. As all known highly ivermectin-sensitive GluClRs contain an endogenous glycine residue at the corresponding location, this residue appears essential for exquisite ivermectin sensitivity. PMID- 20308071 TI - Role of inositol trisphosphate receptors in autophagy in DT40 cells. AB - Previous studies have shown that small interfering RNA knockdown and pharmacological inhibition of inositol 1,4,5-trisphosphate receptors (IP(3)Rs) stimulate autophagy. We have investigated autophagy in chicken DT40 cell lines containing targeted deletions of all three IP(3)R isoforms (triple knock-out (TKO) cells). Using gel shifts of microtubule-associated protein 1 light chain 3 as a marker of autophagy, we find that TKO cells have enhanced basal autophagic flux even under nutrient-replete conditions. Stable DT40 cell lines derived from TKO cells containing the functionally inactive D2550A IP(3)R mutant did not suppress autophagy in the same manner as wild-type receptors. This suggests that the channel function of the receptor is important in its regulatory role in autophagy. There were no marked differences in the phosphorylation state of AMP activated protein kinase, Akt, or mammalian target of rapamycin between wild-type and TKO cells. The amount of immunoprecipitated complexes of Bcl-2-Beclin-1 and Beclin-1-Vps34 were also not different between the two cell lines. The major difference noted was a substantially decreased mTORC1 kinase activity in TKO cells based on decreased phosphorylation of S6 kinase and 4E-BP1. The discharge of intracellular stores with thapsigargin stimulated mTORC1 activity (measured as S6 kinase phosphorylation) to a greater extent in wild-type than in TKO cells. We suggest that basal autophagic flux may be negatively regulated by IP(3)R dependent Ca(2+) signals acting to maintain an elevated mTORC1 activity in wild type cells and that Ca(2+) regulation of this enzyme is defective in TKO cells. The protective effect of a higher autophagic flux in cells lacking IP(3)Rs may play a role in the delayed apoptotic response observed in these cells. PMID- 20308072 TI - Biochemical characterization of the cellular glycosylphosphatidylinositol-linked membrane type-6 matrix metalloproteinase. AB - Ubiquitously expressed membrane type-1 matrix metalloproteinase (MT1-MMP), an archetype member of the MMP family, binds tissue inhibitor of metalloproteinases 2 (TIMP-2), activates matrix metalloproteinase-2 (MMP-2), and stimulates cell migration in various cell types. In contrast with MT1-MMP, the structurally similar MT6-MMP associates with the lipid raft compartment of the plasma membrane using a GPI anchor. As a result, MT6-MMP is functionally distinct from MT1-MMP. MT6-MMP is insufficiently characterized as yet. In addition, a number of its biochemical features are both conflicting and controversial. To reassess the biochemical features of MT6-MMP, we have expressed the MT6-MMP construct tagged with a FLAG tag in breast carcinoma MCF-7 and fibrosarcoma HT1080 cells. We then used phosphatidylinositol-specific phospholipase C to release MT6-MMP from the cell surface and characterized the solubilized MT6-MMP fractions. We now are confident that cellular MT6-MMP partially exists in its complex with TIMP-2. Both TIMP-1 and TIMP-2 are capable of inhibiting the proteolytic activity of MT6-MMP. MT6-MMP does not stimulate cell migration. MT6-MMP, however, generates a significant level of gelatinolysis of the fluorescein isothiocyanate-labeled gelatin and exhibits an intrinsic, albeit low, ability to activate MMP-2. As a result, it is exceedingly difficult to record the activation of MMP-2 by cellular MT6-MMP. Because of its lipid raft localization, cellular MT6-MMP is inefficiently internalized. MT6-MMP is predominantly localized in the cell-to cell junctions. Because MT6-MMP has been suggested to play a role in disease, including cancer and autoimmune multiple sclerosis, the identity of its physiologically relevant cleavage targets remains to be determined. PMID- 20308073 TI - Rescue of cystathionine beta-synthase (CBS) mutants with chemical chaperones: purification and characterization of eight CBS mutant enzymes. AB - Missense mutations represent the most common cause of many genetic diseases including cystathionine beta-synthase (CBS) deficiency. Many of these mutations result in misfolded proteins, which lack biological function. The presence of chemical chaperones can sometimes alleviate or even restore protein folding and activity of mutant proteins. We present the purification and characterization of eight CBS mutants expressed in the presence of chemical chaperones such as ethanol, dimethyl sulfoxide, or trimethylamine-N-oxide. Preliminary screening in Escherichia coli crude extracts showed that their presence during protein expression had a significant impact on the amount of recovered CBS protein, formation of tetramers, and catalytic activity. Subsequently, we purified eight CBS mutants to homogeneity (P49L, P78R, A114V, R125Q, E176K, P422L, I435T, and S466L). The tetrameric mutant enzymes fully saturated with heme had the same or higher specific activities than wild type CBS. Thermal stability measurements demonstrated that the purified mutants are equally or more thermostable than wild type CBS. The response to S-adenosyl-L-methionine stimulation or thermal activation varied. The lack of response of R125Q and E176K to both stimuli indicated that their specific conformations were unable to reach the activated state. Increased levels of molecular chaperones in crude extracts, particularly DnaJ, indicated a rather indirect effect of the chemical chaperones on folding of CBS mutants. In conclusion, the chemical chaperones present in the expression medium were able to fully restore the activity of eight CBS mutants by improving their protein folding. This finding could have direct implications for the development of a therapeutical approach to pyridoxine unresponsive homocystinuria. PMID- 20308074 TI - Functional heterogeneity of CD11c-positive adipose tissue macrophages in diet induced obese mice. AB - Obesity represents a state of chronic, low grade inflammation and is associated with infiltration of increased numbers of adipose tissue macrophages (ATMs). Diet induced obesity leads to an increase in non-inflammatory M1-like ATMs displaying the CD11c surface marker. We assessed the function of CD11c-positive ATMs when insulin resistant high fat diet (HFD) mice become insulin-sensitive after switching from HFD to normal chow (NC). HFD mice rapidly become insulin-sensitive in all major insulin-target tissues, including muscle, liver, and adipose tissue, after the diet switch. In adipose tissue the CD11c-positive macrophages remain constant in number despite the presence of insulin sensitivity, but these macrophages now assume a new phenotype in which they no longer exhibit increased inflammatory pathway markers. Adipose tissue markers of apoptosis and necrosis were elevated on HFD and remain high after the HFD --> NC diet switch. Furthermore, ATM accumulation preceded detectable adipocyte necrosis at the early phase of HFD. Together, these results indicate that 1) CD11c-positive M1-like ATMs can exhibit phenotypic plasticity and that the polarization of these cells between inflammatory and non-inflammatory states is well correlated to the presence of absence of insulin resistance, and 2) adipocyte necrosis and apoptosis can be dissociated from ATM accumulation. PMID- 20308075 TI - A putative extracellular salt bridge at the subunit interface contributes to the ion channel function of the ATP-gated P2X2 receptor. AB - The recent crystal structure of the ATP-gated P2X4 receptor revealed a static view of its architecture, but the molecular mechanisms underlying the P2X channels activation are still unknown. By using a P2X2 model based on the x-ray structure, we sought salt bridges formed between charged residues located in a region that directly connects putative ATP-binding sites to the ion channel. To reveal their significance for ion channel activation, we made systematic charge exchanges and measured the effects on ATP sensitivity. We found that charge reversals at the interfacial residues Glu(63) and Arg(274) produced gain-of function phenotypes that were cancelled upon paired charge swapping. These results suggest that a putative intersubunit salt bridge formed between Glu(63) and Arg(274) contributes to the ion channel function. Engineered cysteines E63C and R274C formed redox-dependent cross-links in the absence of ATP. By contrast, the presence of ATP reduced the rate of disulfide bond formation, indicating that ATP binding might trigger relative movement of adjacent subunits at the level of Glu(63) and Arg(274), allowing the transmembrane helices to open the channel. PMID- 20308076 TI - Temporin-SHf, a new type of phe-rich and hydrophobic ultrashort antimicrobial peptide. AB - Because issues of cost and bioavailability have hampered the development of gene encoded antimicrobial peptides to combat infectious diseases, short linear peptides with high microbial cell selectivity have been recently considered as antibiotic substitutes. A new type of short antimicrobial peptide, designated temporin-SHf, was isolated and cloned from the skin of the frog Pelophylax saharica. Temporin-SHf has a highly hydrophobic sequence (FFFLSRIFa) and possesses the highest percentage of Phe residues of any known peptide or protein. Moreover, it is the smallest natural linear antimicrobial peptide found to date, with only eight residues. Despite its small size and hydrophobicity, temporin-SHf has broad-spectrum microbicidal activity against Gram-positive and Gram-negative bacteria and yeasts, with no hemolytic activity. CD and NMR spectroscopy combined with restrained molecular dynamics calculations showed that the peptide adopts a well defined non-amphipathic alpha-helical structure from residue 3 to 8, when bound to zwitterionic dodecyl phosphocholine or anionic SDS micelles. Relaxation enhancement caused by paramagnetic probes showed that the peptide adopts nearly parallel orientations to the micelle surface and that the helical structure is stabilized by a compact hydrophobic core on one face that penetrates into the micelle interior. Differential scanning calorimetry on multilamellar vesicles combined with membrane permeabilization assays on bacterial cells indicated that temporin-SHf disrupts the acyl chain packing of anionic lipid bilayers, thereby triggering local cracks and microbial membrane disintegration through a detergent like effect probably via the carpet mechanism. The short length, compositional simplicity, and broad-spectrum activity of temporin-SHf make it an attractive candidate to develop new antibiotic agents. PMID- 20308077 TI - Aspartic acid racemization and collagen degradation markers reveal an accumulation of damage in tendon collagen that is enhanced with aging. AB - Little is known about the rate at which protein turnover occurs in living tendon and whether the rate differs between tendons with different physiological roles. In this study, we have quantified the racemization of aspartic acid to calculate the age of the collagenous and non-collagenous components of the high strain injury-prone superficial digital flexor tendon (SDFT) and low strain rarely injured common digital extensor tendon (CDET) in a group of horses with a wide age range. In addition, the turnover of collagen was assessed indirectly by measuring the levels of collagen degradation markers (collagenase-generated neoepitope and cross-linked telopeptide of type I collagen). The fractional increase in D-Asp was similar (p = 0.7) in the SDFT (5.87 x 10(-4)/year) and CDET (5.82 x 10(-4)/year) tissue, and D/L-Asp ratios showed a good correlation with pentosidine levels. We calculated a mean (+/-S.E.) collagen half-life of 197.53 (+/-18.23) years for the SDFT, which increased significantly with horse age (p = 0.03) and was significantly (p < 0.001) higher than that for the CDET (34.03 (+/ 3.39) years). Using similar calculations, the half-life of non-collagenous protein was 2.18 (+/-0.41) years in the SDFT and was significantly (p = 0.04) lower than the value of 3.51 (+/-0.51) years for the CDET. Collagen degradation markers were higher in the CDET and suggested an accumulation of partially degraded collagen within the matrix with aging in the SDFT. We propose that increased susceptibility to injury in older individuals results from an inability to remove partially degraded collagen from the matrix leading to reduced mechanical competence. PMID- 20308078 TI - MDM2 promotes proteasomal degradation of p21Waf1 via a conformation change. AB - MDM2 plays a major role in cancer development and progression via both p53 dependent and -independent functions. One of its p53-independent functions is the induction of the ubiquitin-independent proteasomal degradation of p21(Waf1). The present study was designed to characterize the mechanism(s) by which MDM2 induces p21(Waf1) degradation. We first determined the regions of MDM2 required for p21(Waf1) degradation using pulldown assays and Western blotting and then examined the mechanisms using limited proteolysis and fluorescence resonance energy transfer assays. We found that the MDM2-p21(Waf1) interaction depended on the central domain of MDM2 and that nuclear localization of both proteins was necessary for p21(Waf1) degradation. Specifically, amino acids 226-250 of MDM2 were required for p21(Waf1) binding and degradation, and amino acids 251-260 were necessary for p21(Waf1) degradation. The latter region induced a conformation change in p21(Waf1), increasing its interaction with the C8 subunit of the proteasome, leading to its degradation. When MDM2 lacked either segment (aa 226 250 or aa 251-260), its capacity to promote p21(Waf1) degradation and cell cycle progression was significantly reduced. In summary, the present study elucidated a previously unknown mechanism by which MDM2 promotes the degradation of an intact protein (p21(Waf1)) through an ubiquitin-independent proteasomal degradation pathway. Because MDM2 also increases the degradation of other proteins in a ubiquitin-independent manner, this mechanism may underlie part of its tumorigenic properties. PMID- 20308079 TI - Long chain acyl-CoA synthetase-3 is a molecular target for peroxisome proliferator-activated receptor delta in HepG2 hepatoma cells. AB - ACSL3 is a member of the long chain acyl-CoA synthetase (ACSL) family that plays key roles in fatty acid metabolism in various tissues in an isozyme-specific manner. Our previous studies showed that ACSL3 was transcriptionally up-regulated by the cytokine oncostatin M (OSM) in HepG2 cells, accompanied by reduced cellular triglyceride content and enhanced beta-oxidation. In this study, we investigated the molecular mechanism underlying the OSM-induced activation of ACSL3 gene transcription in HepG2 cells. We showed that OSM treatment resulted in a coordinated elevation of mRNA levels of ACSL3 and peroxisome proliferator activated receptor delta (PPARdelta). The effect of OSM on ACSL3 mRNA expression was inhibited by cellular depletion of PPARdelta. By utilizing a PPARdelta agonist, L165041, we demonstrated that activation of PPARdelta led to increases in ACSL3 promoter activity, mRNA level, and protein level in HepG2 cells. Analysis of the ACSL3 promoter sequence identified two imperfect PPAR-responsive elements (PPRE) located in the ACSL3 promoter region -944 to -915, relative to the transcription start site. The up-regulation of ACSL3 promoter activity by PPARdelta was abolished by deletion of this PPRE-containing region or mutation to disrupt the binding sites. Direct interactions of PPARdelta with ACSL3-PPRE sequences were demonstrated by gel mobility shift and chromatin immunoprecipitation assays. Finally, we provided in vivo evidence showing that activation of PPARdelta by L165041 in hamsters increased ACSL3 mRNA and protein levels in the liver. These new findings define ACSL3 as a novel molecular target of PPARdelta in HepG2 cells and provide a regulatory mechanism for ACSL3 transcription in liver tissue. PMID- 20308080 TI - Polydactyl inheritance in the pig. AB - Two pigs were identified having "extra feet" (preaxial polydactyly) within a purebred population of Yorkshire pigs. Polydactyly is an inherited disorder in many species that may be controlled by either recessive or dominant genes. Experimental matings were conducted using pigs that had produced affected offspring with the result of 12 polydactyl offspring out of 95 piglets. One polydactyl-producing boar was also mated to 4 Duroc sows and 8 distantly related Yorkshire sows to produce 129 unaffected offspring. Together, these results suggest a recessive mode of inheritance, possibly with incomplete penetrance. Candidate genes, LMBR1, EN2, HOXA10-13, GLI3, WNT2, WNT16, and SHH, were identified based on association with similar phenotypes in other species. Homologues for these genes are all found on SSC18. Sequencing and linkage studies showed no evidence for association with HOXA10-13, WNT2, and WNT16. Results for the regions including GLI3, LMBR1, and SHH, however, were inconclusive. A whole genome scan was conducted on DNA samples from 10 affected pigs and 12 close relatives using the Illumina PorcineSNP60 BeadChip and compared with 69 more distantly related animals in the same population. No evidence was found for a major gene causing polydactyly. However, a 25-Mb stretch of homozygosity on SSC8 was identified as fairly unique to the family segregating for this trait. Therefore, this chromosome segment may play a role in development of polydactyly in concert with other genes. PMID- 20308081 TI - Microsatellite analyses provide evidence of male-biased dispersal in the radiated tortoise Astrochelys radiata (Chelonia: Testudinidae). AB - Dispersal is a major force in shaping the genetic structure and dynamics of species; thus, its understanding is critical in formulating appropriate conservation strategies. In many species, sexes do not face the same evolutionary pressures, and consequently dispersal is often asymmetrical between males and females. This is well documented in birds and mammals but has seldom been investigated in other taxa, including reptiles and, more specifically, nonmarine chelonians. In these species, nest-site fidelity observations are frequent but still remain to be associated with natal homing. Here, we tested for sex-biased dispersal in the radiated tortoise (Astrochelys radiata) from southern Madagascar. Using data from 13 microsatellite markers, we investigated patterns of relatedness between sexes in 2 populations. All Mantel tests indicated significant isolation by distance at the individual level in females but not in males. Furthermore, spatial autocorrelation analyses and 2 analytical approaches designed to assess general trends in sex-specific dispersal also supported male biased dispersal. On the other hand, comparisons of overall genetic structure among sampling sites did not provide conclusive support for greater philopatry in females, but these tests may have low statistical power because of methodological and biological constraints. Radiated tortoises appear to be both polyandrous and polygynous, and evolutionary processes that may lead to a sex bias in dispersal are discussed with respect to tortoise breeding biology. Female natal homing is hypothesized as a key trait explaining greater female philopatry in A. radiata. These findings highlight the necessity of additional research on natal homing in tortoises, a behavioral trait with direct implications for conservation. PMID- 20308083 TI - Response to "Radiation therapeutic gain and Asian botanicals," by Stephen Sagar. AB - Numerous botanical agents, many of which are used in whole medical system practices (i.e. traditional Chinese medicine, Ayurvedic medicine, etc.), have been shown to exhibit radiomodifying effects on tumors and normal tissues in vitro and in-vivo studies. Some of these agents can enhance the therapeutic gain of radiation therapy by either acting as a radiosensitizer to tumor cells and/or as a radioprotector to normal cells. Botanical agents are comprised of multiple phytochemical compounds that may work individually or synergistically to not only improve radiation therapy outcomes, but may also exhibit a variety of anti-cancer effects as well. It will be important to evaluate these botanicals for efficacy, tumor specificity, and safety profiles before they can be recommended during radiation therapy. PMID- 20308084 TI - Prevalence, patterns, and costs of Chinese medicine use among prostate cancer patients: a population-based study in Taiwan. AB - BACKGROUND: Taiwan's National Health Insurance (NHI) is a comprehensive and universal program, providing Western medicine (WM) and Chinese medicine (CM). This study aims to explore CM use among prostate cancer patients in NHI. METHODS: A cross-section retrospective analysis was conducted using registration and claim data sets from the NHI Research Database. In 2007, 22,352 prostate cancer patients with 265,497 visits of CM and WM ambulatory services were identified. Patient demographics, patterns of therapies, and costs were analyzed. RESULTS: In 2007, 592 prostate cancer patients (2.6%) had 4141 CM outpatient visits (7.0 on average). The median age was 73.9. The majority (90.5%) of CM users also used WM ambulatory services. About one third of CM outpatient services were provided by private clinics. The most frequently used CM therapies were Chinese herbal medication (93.6%), followed by acupuncture/traumatology manipulative therapies (7.0%). CM accounted for 0.2% expenditure ($87,500) and 1.6% visits of ambulatory services. The average cost per visit for WM was 6.3 times higher than that for CM ($133.6 vs $21). CONCLUSIONS: The prevalence and costs of insurance-covered CM among prostate cancer patients were low. Most prostate cancer patients did not use insurance-covered CM. The majority of CM users also used WM. CM appeared to play a complementary rather than an alternative role. PMID- 20308085 TI - Ski acts as therapeutic target of qingyihuaji formula in the treatment of SW1990 pancreatic cancer. AB - BACKGROUND: Qingyihuaji formula (QYHJ) is a widely used herbal formula that has shown promising antitumor effect in the treatment of pancreatic cancer in the Cancer Hospital, Fudan University, Shanghai, China. OBJECTIVE: This research was conducted to study whether Ski acts as a therapeutic target of QYHJ formula in the treatment of SW1990 pancreatic cancer. METHODS: The expression changes of Ski mRNA and protein in SW1990 pancreatic cancer subcutaneously transplanted tumor treated with QYHJ were detected by real-time polymerase chain reaction and Western blot. Then, we established a stable transfection SW1990 cell with low expression of Ski through lentivirus-mediated RNA interference (RNAi) technique. The responses to QYHJ treatment on a subcutaneously transplanted tumor with different Ski expression statuses were evaluated. Finally, the effect of Ski downregulation on SW1990 cell biological behavior was also evaluated. RESULTS: Expression of Ski mRNA and protein in SW1990 subcutaneously transplanted tumor decreased dramatically after the treatment with QYHJ. Stable transfection cells with low expression of Ski (SW1990/Ski RNAi) were created, and negative vector transfected cells (SW1990/con RNAi) were used as controls. The tumor weight inhibitory rates of QYHJ on subcutaneously transplanted tumors formed by SW1990 or SW1990/con RNAi were 29.6% and 32.2%, respectively, whereas they were 16.0% to 17.8% when the tumors were formed by SW1990/Ski RNAi. Ski downregulation sensitized the response of SW1990 cells to TGF-beta1-induced growth inhibition in vitro. Flow cytometric analyses revealed that the percentage of cells in the G1 phase increased from 40.4% to 62.9% when Ski was downregulated. The subcutaneously transplanted tumors formed by SW1990/Ski RNAi grew much more slowly than those formed by parental and control vector-transfected cells. CONCLUSION: Ski acts as therapeutic target of QYHJ in the treatment of SW1990 pancreatic cancer cells, and its expression status mediates different responses to QYHJ treatment. PMID- 20308086 TI - Toxicity and cytopathogenic properties toward human melanoma cells of activated cancer therapeutics in zebra fish. AB - There is an increasing body of data showing that activated cancer therapy--the synergistic effect of "preloaded" molecules and a tuned energy source to produce cytopathogenic moieties--is a promising new modality for cancer treatment. The key activated therapies are photodynamic therapy (PDT), which involves the synergy between light and photosensitizer molecules, and ultrasound activated therapy (USAT; also referred to as sonodynamic therapy), which involves the synergy between ultrasound and sonosensitizer molecules. PDT is a well-known activated therapy with roots dating back to 1900. However, minimal data exist on USAT. One reason is the lack of suitable sonosensitizers for clinical USAT use. The authors present both LC(50) toxicity and cancer cell cytotoxicity studies on 2 dual activation agents. These compounds function as both sonosensitizers and photosensitizers, and are referred to as SonneLux agents, designated SF1 and SF2. The sensitizers are derived from chlorophyll and are metal centered porphyrins known to specifically accumulate in hyperproliferating tissue. LC(50) studies on both SF1 and SF2 as determined in zebra fish reveal that both are essentially nontoxic to zebra fish. In the worst case, 5% zebra fish death is noted at the maximum soluble concentration of the sensitizer. In the cytotoxicity studies, melanoma cell line WM-266-4, derived from a metastatic site of a malignant melanoma, was tested against SF1 and SF2. Both sensitizer systems showed marked efficacy in the destruction of the implanted melanoma cells. They show great promise for clinical use in the future. PMID- 20308087 TI - A case of recurred hepatocellular carcinoma refractory to doxorubicin after liver transplantation showing response to herbal medicine product, Rhus verniciflua Stokes extract. AB - There is no established protocol proven to be beneficial for treatment of hepatocellular carcinoma recurrence after liver transplantation. Only a few reports have shown direct treatment by surgery or ablation to be independent predictors of survival for localized recurrence. Moreover, the necessity of immunosuppression to prevent allograft rejection makes many physicians hesitate to administer systemic chemotherapy. This case report documents a case in which the administration of an herbal product, an extract of the lacquer tree, Rhus verniciflua Stokes, was associated with a decrease in the size of lung metastases in a patient with recurrent hepatocellular carcinoma after liver transplantation refractory to doxorubicin. This patient experienced prolonged survival compared with average survival times and little toxicity. PMID- 20308089 TI - Mutations and Brian Charlesworth. PMID- 20308090 TI - The population genetics of mutations: good, bad and indifferent. AB - Population genetics is fundamental to our understanding of evolution, and mutations are essential raw materials for evolution. In this introduction to more detailed papers that follow, we aim to provide an oversight of the field. We review current knowledge on mutation rates and their harmful and beneficial effects on fitness and then consider theories that predict the fate of individual mutations or the consequences of mutation accumulation for quantitative traits. Many advances in the past built on models that treat the evolution of mutations at each DNA site independently, neglecting linkage of sites on chromosomes and interactions of effects between sites (epistasis). We review work that addresses these limitations, to predict how mutations interfere with each other. An understanding of the population genetics of mutations of individual loci and of traits affected by many loci helps in addressing many fundamental and applied questions: for example, how do organisms adapt to changing environments, how did sex evolve, which DNA sequences are medically important, why do we age, which genetic processes can generate new species or drive endangered species to extinction, and how should policy on levels of potentially harmful mutagens introduced into the environment by humans be determined? PMID- 20308091 TI - Measurements of spontaneous rates of mutations in the recent past and the near future. AB - The rate of spontaneous mutation in natural populations is a fundamental parameter for many evolutionary phenomena. Because the rate of mutation is generally low, most of what is currently known about mutation has been obtained through indirect, complex and imprecise methodological approaches. However, in the past few years genome-wide sequencing of closely related individuals has made it possible to estimate the rates of mutation directly at the level of the DNA, avoiding most of the problems associated with using indirect methods. Here, we review the methods used in the past with an emphasis on next generation sequencing, which may soon make the accurate measurement of spontaneous mutation rates a matter of routine. PMID- 20308092 TI - Rate and effects of spontaneous mutations that affect fitness in mutator Escherichia coli. AB - Knowledge of the mutational parameters that affect the evolution of organisms is of key importance in understanding the evolution of several characteristics of many natural populations, including recombination and mutation rates. In this study, we estimated the rate and mean effect of spontaneous mutations that affect fitness in a mutator strain of Escherichia coli and review some of the estimation methods associated with mutation accumulation (MA) experiments. We performed an MA experiment where we followed the evolution of 50 independent mutator lines that were subjected to repeated bottlenecks of a single individual for approximately 1150 generations. From the decline in mean fitness and the increase in variance between lines, we estimated a minimum mutation rate to deleterious mutations of 0.005 (+/-0.001 with 95% confidence) and a maximum mean fitness effect per deleterious mutation of 0.03 (+/-0.01 with 95% confidence). We also show that any beneficial mutations that occur during the MA experiment have a small effect on the estimate of the rate and effect of deleterious mutations, unless their rate is extremely large. Extrapolating our results to the wild-type mutation rate, we find that our estimate of the mutational effects is slightly larger and the inferred deleterious mutation rate slightly lower than previous estimates obtained for non-mutator E. coli. PMID- 20308093 TI - What can we learn about the distribution of fitness effects of new mutations from DNA sequence data? AB - We investigate several questions concerning the inference of the distribution of fitness effects (DFE) of new mutations from the distribution of nucleotide frequencies in a population sample. If a fixed sequencing effort is available, we find that the optimum strategy is to sequence a modest number of alleles (approx. 10). If full genome information is available, the accuracy of parameter estimates increases as the number of alleles sequenced increases, but with diminishing returns. It is unlikely that the DFE for single genes can be reliably estimated in organisms such as humans and Drosophila, unless genes are very large and we sequence hundreds or perhaps thousands of alleles. We consider models involving several discrete classes of mutations in which the selection strength and density apportioned to each class can vary. Models with three classes fit almost as well as four class models unless many hundreds of alleles are sequenced. Large numbers of alleles need to be sequenced to accurately estimate the distribution's mean and variance. Estimating complex DFEs may therefore be difficult. Finally, we examine models involving slightly advantageous mutations. We show that the distribution of the absolute strength of selection is well estimated if mutations are assumed to be unconditionally deleterious. PMID- 20308094 TI - The population genetics of beneficial mutations. AB - The population genetic study of advantageous mutations has lagged behind that of deleterious and neutral mutations. But over the past two decades, a number of significant developments, both theoretical and empirical, have occurred. Here, I review two of these developments: the attempt to determine the distribution of fitness effects among beneficial mutations and the attempt to determine their average dominance. Considering both theory and data, I conclude that, while considerable theoretical progress has been made, we still lack sufficient data to draw confident conclusions about the distribution of effects or the dominance of beneficial mutations. PMID- 20308095 TI - Forces that influence the evolution of codon bias. AB - The frequencies of alternative synonymous codons vary both among species and among genes from the same genome. These patterns have been inferred to reflect the action of natural selection. Here we evaluate this in bacteria. While intragenomic variation in many species is consistent with selection favouring translationally optimal codons, much of the variation among species appears to be due to biased patterns of mutation. The strength of selection on codon usage can be estimated by two different approaches. First, the extent of bias in favour of translationally optimal codons in highly expressed genes, compared to that in genes where selection is weak, reveals the long-term effectiveness of selection. Here we show that the strength of selected codon usage bias is highly correlated with bacterial growth rate, suggesting that selection has favoured translational efficiency. Second, the pattern of bias towards optimal codons at polymorphic sites reveals the ongoing action of selection. Using this approach we obtained results that were completely consistent with the first method; importantly, the frequency spectra of optimal codons at polymorphic sites were similar to those predicted under an equilibrium model. Highly expressed genes in Escherichia coli appear to be under continuing strong selection, whereas selection is very weak in genes expressed at low levels. PMID- 20308096 TI - What drives recombination hotspots to repeat DNA in humans? AB - Recombination between homologous, but non-allelic, stretches of DNA such as gene families, segmental duplications and repeat elements is an important source of mutation. In humans, recent studies have identified short DNA motifs that both determine the location of 40 per cent of meiotic cross-over hotspots and are significantly enriched at the breakpoints of recurrent non-allelic homologous recombination (NAHR) syndromes. Unexpectedly, the most highly penetrant form of the motif occurs on the background of an inactive repeat element family (THE1 elements) and the motif also has strong recombinogenic activity on currently active element families including Alu and LINE2 elements. Analysis of genetic variation among members of these repeat families indicates an important role for NAHR in their evolution. Given the potential for double-strand breaks within repeat DNA to cause pathological rearrangement, the association between repeats and hotspots is surprising. Here we consider possible explanations for why selection acting against NAHR has not eliminated hotspots from repeat DNA including mechanistic constraints, possible benefits to repeat DNA from recruiting hotspots and rapid evolution of the recombination machinery. I suggest that rapid evolution of hotspot motifs may, surprisingly, tend to favour sequences present in repeat DNA and outline the data required to differentiate between hypotheses. PMID- 20308097 TI - Transposable elements in natural populations of Drosophila melanogaster. AB - Transposable elements (TEs) are families of small DNA sequences found in the genomes of virtually all organisms. The sequences typically encode essential components for the replicative transposition sequences of that TE family. Thus, TEs are simply genomic parasites that inflict detrimental mutations on the fitness of their hosts. Several models have been proposed for the containment of TE copy number in outbreeding host populations such as Drosophila. Surveys of the TEs in genomes from natural populations of Drosophila have played a central role in the investigation of TE dynamics. The early surveys indicated that a typical TE insertion is rare in a population, which has been interpreted as evidence that each TE is selected against. The proposed mechanisms of this natural selection are reviewed here. Subsequent and more targeted surveys identify heterogeneity among types of TEs and also highlight the large role of homologous and possibly ectopic crossing over in the dynamics of the Drosophila TEs. The recent discovery of germline-specific RNA interference via the piwi-interacting RNA pathway opens yet another interesting mechanism that may be critical in containing the copy number of TEs in natural populations of Drosophila. The expected flood of Drosophila population genomics is expected to rapidly advance understanding of the dynamics of TEs. PMID- 20308099 TI - On epistasis: why it is unimportant in polygenic directional selection. AB - There is a difference in viewpoint of developmental and evo-devo geneticists versus breeders and students of quantitative evolution. The former are interested in understanding the developmental process; the emphasis is on identifying genes and studying their action and interaction. Typically, the genes have individually large effects and usually show substantial dominance and epistasis. The latter group are interested in quantitative phenotypes rather than individual genes. Quantitative traits are typically determined by many genes, usually with little dominance or epistasis. Furthermore, epistatic variance has minimum effect, since the selected population soon arrives at a state in which the rate of change is given by the additive variance or covariance. Thus, the breeder's custom of ignoring epistasis usually gives a more accurate prediction than if epistatic variance were included in the formulae. PMID- 20308098 TI - Mutations and quantitative genetic variation: lessons from Drosophila. AB - A central issue in evolutionary quantitative genetics is to understand how genetic variation for quantitative traits is maintained in natural populations. Estimates of genetic variation and of genetic correlations and pleiotropy among multiple traits, inbreeding depression, mutation rates for fitness and quantitative traits and of the strength and nature of selection are all required to evaluate theoretical models of the maintenance of genetic variation. Studies in Drosophila melanogaster have shown that a substantial fraction of segregating variation for fitness-related traits in Drosophila is due to rare deleterious alleles maintained by mutation-selection balance, with a smaller but significant fraction attributable to intermediate frequency alleles maintained by alleles with antagonistic pleiotropic effects, and late-age-specific effects. However, the nature of segregating variation for traits under stabilizing selection is less clear and requires more detailed knowledge of the loci, mutation rates, allelic effects and frequencies of molecular polymorphisms affecting variation in suites of pleiotropically connected traits. Recent studies in D. melanogaster have revealed unexpectedly complex genetic architectures of many quantitative traits, with large numbers of pleiotropic genes and alleles with sex-, environment- and genetic background-specific effects. Future genome wide association analyses of many quantitative traits on a common panel of fully sequenced Drosophila strains will provide much needed empirical data on the molecular genetic basis of quantitative traits. PMID- 20308100 TI - Genetic hitchhiking versus background selection: the controversy and its implications. AB - The controversy on the relative importance of background selection (BGS; against deleterious mutations) and genetic hitchhiking (associated with positive directional selection) in explaining patterns of nucleotide variation in natural populations stimulated research activities for almost a decade. Despite efforts from many theorists and empiricists, fundamental questions are still open, in particular, for the population genetics of regions of reduced recombination. On the other hand, the development of the BGS and hitchhiking models and the long struggle to distinguish them, all of which seem to be a purely academic exercise, led to quite practical advances that are useful for the identification of genes involved in adaptation and domestication. PMID- 20308101 TI - Beneficial mutations and the dynamics of adaptation in asexual populations. AB - We discuss the dynamics of adaptive evolution in asexual (clonal) populations. The classical 'periodic selection' model of clonal evolution assumed that beneficial mutations are very rare and therefore substitute unfettered into populations as occasional, isolated events. Newer models allow for the possibility that beneficial mutations are sufficiently common to coexist and compete for fixation within populations. Experimental evolution studies in microbes provide empirical support for stochastic models in which both selection and mutation are strong effects and clones compete for fixation; however, the relative importance of competition among clones bearing mutations of different selective effects versus competition among clones bearing multiple mutations remains unresolved. We provide some new theoretical results, moreover, suggesting that population dynamics consistent with the periodic selection model can arise even in a deterministic model that can accommodate a very high beneficial mutation rate. PMID- 20308102 TI - The role of meiotic drive in hybrid male sterility. AB - Meiotic drive causes the distortion of allelic segregation away from Mendelian expected ratios, often also reducing fecundity and favouring the evolution of drive suppressors. If different species evolve distinct drive-suppressor systems, then hybrid progeny may be sterile as a result of negative interactions of these systems' components. Although the hypothesis that meiotic drive may contribute to hybrid sterility, and thus species formation, fell out of favour early in the 1990s, recent results showing an association between drive and sterility have resurrected this previously controversial idea. Here, we review the different forms of meiotic drive and their possible roles in speciation. We discuss the recent empirical evidence for a link between drive and hybrid male sterility, also suggesting a possible mechanistic explanation for this link in the context of chromatin remodelling. Finally, we revisit the population genetics of drive that allow it to contribute to speciation. PMID- 20308103 TI - Mutation and the evolution of ageing: from biometrics to system genetics. AB - A notable success for evolutionary genetics during the past century was to generate a coherent, quantitative explanation for an apparent evolutionary paradox: the tendency for multicellular organisms to show declining fitness with age (senescence, often referred to simply as 'ageing'). This general theory is now widely accepted and explains most of the features of senescence that are observed in natural and laboratory populations, but specific instantiations of that theory have been more controversial. To date, most of the empirical tests of these models have relied on data generated from biometric experiments. Modern population genetics and genomics provide new, and probably more powerful, ways to test ideas that are still controversial more than half a century after the original theory was developed. System-genetic experiments have the potential to address both evolutionary and mechanistic questions about ageing by identifying causal loci and the genetic networks with which they interact. Both the biometrical approaches and the newer approaches are reviewed here, with an emphasis on the challenges and limitations that each method faces. PMID- 20308105 TI - The next generation of biomaterial development. PMID- 20308104 TI - Mutation and the evolution of recombination. AB - Under the classical view, selection depends more or less directly on mutation: standing genetic variance is maintained by a balance between selection and mutation, and adaptation is fuelled by new favourable mutations. Recombination is favoured if it breaks negative associations among selected alleles, which interfere with adaptation. Such associations may be generated by negative epistasis, or by random drift (leading to the Hill-Robertson effect). Both deterministic and stochastic explanations depend primarily on the genomic mutation rate, U. This may be large enough to explain high recombination rates in some organisms, but seems unlikely to be so in general. Random drift is a more general source of negative linkage disequilibria, and can cause selection for recombination even in large populations, through the chance loss of new favourable mutations. The rate of species-wide substitutions is much too low to drive this mechanism, but local fluctuations in selection, combined with gene flow, may suffice. These arguments are illustrated by comparing the interaction between good and bad mutations at unlinked loci under the infinitesimal model. PMID- 20308106 TI - Building off-the-shelf tissue-engineered composites. AB - Rapid advances in technology have created the realistic possibility of personalized medicine. In 2000, Time magazine listed tissue engineering as one of the 'hottest 10 career choices'. However, in the past decade, only a handful of tissue-engineered products were translated to the clinical market and none were financially viable. The reality of complex business planning and the high investment, high-technology environment was not apparent, and the promise of tissue engineering was overstated. In the meantime, biologists were steadily applying three-dimensional benchtop tissue-culture systems for cellular research, but the systems were gelatinous and thus limited in their ability to facilitate the development of complex tissues. Now, the bioengineering literature has seen an emergence of literature describing biofabrication of tissues and organs. However, if one looks closely, again, the viable products appear distant. 'Rapid' prototyping to reproduce the intricate patterns of whole organs using large volumes of cellular components faces daunting challenges. Homogenous forms are being labelled 'tissues', but, in fact, do not represent the heterogeneous structure of the native biological system. In 2003, we disclosed the concept of combining rapid prototyping techniques with tissue engineering technologies to facilitate precision development of heterogeneous complex tissue-test systems, i.e. systems to be used for drug discovery and the study of cellular behaviour, biomedical devices and progression of disease. The focus of this paper is on the challenges we have faced since that time, moving this concept towards reality, using the case of breast tissue as an example. PMID- 20308107 TI - Wetting behaviour of laser synthetic surface microtextures on Ti-6Al-4V for bioapplication. AB - Wettability at the surface of an implant material plays a key role in its success as it modulates the protein adsorption and thereby influences cell attachment and tissue integration at the interface. Hence, surface engineering of implantable materials to enhance wettability to physiological fluid under in vivo conditions is an area of active research. In light of this, in the present work, laser-based optical interference and direct melting techniques were used to develop synthetic microtextures on Ti-6Al-4V alloys, and their effects on wettability were studied systematically. Improved wettability to simulated body fluid and distilled water was observed for Ca-P coatings obtained by direct melting technique. This superior wettability was attributed to both the appropriate surface chemistry and the three-dimensional surface features obtained using this technique. To assert a better control on surface texture and wettability, a three-dimensional thermal model based on COMSOL's multiphysics was employed to predict the features obtained by laser melting technique. The effect of physical texture and wetting on biocompatibility of laser-processed Ca-P coatings was evaluated in the preliminary efforts on culturing of mouse MC3T3-E1 osteoblast cells. PMID- 20308108 TI - Vascular tissue engineering by computer-aided laser micromachining. AB - Many conventional technologies for fabricating tissue engineering scaffolds are not suitable for fabricating scaffolds with patient-specific attributes. For example, many conventional technologies for fabricating tissue engineering scaffolds do not provide control over overall scaffold geometry or over cell position within the scaffold. In this study, the use of computer-aided laser micromachining to create scaffolds for vascular tissue networks was investigated. Computer-aided laser micromachining was used to construct patterned surfaces in agarose or in silicon, which were used for differential adherence and growth of cells into vascular tissue networks. Concentric three-ring structures were fabricated on agarose hydrogel substrates, in which the inner ring contained human aortic endothelial cells, the middle ring contained HA587 human elastin and the outer ring contained human aortic vascular smooth muscle cells. Basement membrane matrix containing vascular endothelial growth factor and heparin was to promote proliferation of human aortic endothelial cells within the vascular tissue networks. Computer-aided laser micromachining provides a unique approach to fabricate small-diameter blood vessels for bypass surgery as well as other artificial tissues with complex geometries. PMID- 20308109 TI - The role of disc-type crystal shape for micromechanical predictions of elasticity and strength of hydroxyapatite biomaterials. AB - The successful design of ceramic bone biomaterials is challenged by two competing requirements: on the one hand, such materials need to be stiff and strong, which would suggest a low porosity (of pore sizes in the 10-100 microm range) to be targeted; on the other hand, bone biomaterials need to be bioactive (in particular vascularized), which suggests a high porosity of such materials. Conclusively, reliable information on how porosity drives the stiffness and strength properties of ceramic bone biomaterials (tissue engineering scaffolds) is of great interest. In this context, mathematical models are increasingly being introduced into the field. Recently, self-consistent continuum micromechanics formulations have turned out as expressedly efficient and reliable tools to predict hydroxyapatite biomaterials' stiffness and strength, as a function of the biomaterial-specific porosity, and of the 'universal' properties of the individual hydroxyapatite crystals: their stiffness, strength and shape. However, the precise crystal shape can be suitably approximated by specific ellipsoidal shapes: while it was shown earlier that spherical shapes do not lead to satisfactory results, and that acicular shapes are an appropriate choice, we here concentrate on disc-type crystal shape as, besides needles, plates are often reported in micrographs of hydroxyapatite biomaterials. Disc-based model predictions of a substantial set of experimental data on stiffness and strength of hydroxyapatite biomaterials almost attain the quality of the very satisfactory needle-based models. This suggests that, as long as the crystal shape is clearly non-spherical, its precise shape is of secondary importance if stiffness and strength of hydroxyapatite biomaterials are predicted on the basis of continuum micromechanics, from their micromorphology and porosity. PMID- 20308110 TI - Molecular mechanisms of crystallization impacting calcium phosphate cements. AB - The biomineral calcium hydrogen phosphate dihydrate (CaHPO(4).2H(2)O), known as brushite, is a malleable material that both grows and dissolves faster than most other calcium minerals, including other calcium phosphate phases, calcium carbonates and calcium oxalates. Within the body, this ready formation and dissolution can play a role in certain diseases, such as kidney stone and plaque formation. However, these same properties, along with brushite's excellent biocompatibility, can be used to great benefit in making resorbable biomedical cements. To optimize cements, additives are commonly used to control crystallization kinetics and phase transformation. This paper describes the use of in situ scanning probe microscopy to investigate the role of several solution parameters and additives in brushite atomic step motion. Surprisingly, this work demonstrates that the activation barrier for phosphate (rather than calcium) incorporation limits growth kinetics and that additives such as magnesium, citrate and bisphosphonates each influence step motion in distinctly different ways. Our findings provide details of how, and where, molecules inhibit or accelerate kinetics. These insights have the potential to aid in designing molecules to target specific steps and to guide synergistic combinations of additives. PMID- 20308111 TI - Use of unnatural amino acids for design of novel organomodified clays as components of nanocomposite biomaterials. AB - Sodium montmorillonite (Na-MMT) clay was modified with three different unnatural amino acids in order to design intercalated clay structures that may be used for bone biomaterials applications. Prior work on polymer-clay nanocomposites (PCNs) has indicated the effect of the appropriate choice of modifiers on enhancing properties of PCNs. Our X-ray diffraction results indicate an increase in the d spacing of Na-MMT clay after it was modified with the three unnatural amino acids. Transmission Fourier transform infrared spectroscopy experiments were carried out on the unmodified and modified MMT clay samples to study the molecular interactions between the amino acids used as modifiers and the Na-MMT clay. Cell culture experiments showed that the Na-MMT clay modified with the three amino acids was biocompatible as were the modified clay-incorporated films of chitosan/polygalacturonic acid/hydroxyapatite. PMID- 20308112 TI - Novel synthesis strategies for natural polymer and composite biomaterials as potential scaffolds for tissue engineering. AB - Recent developments in tissue engineering approaches frequently revolve around the use of three-dimensional scaffolds to function as the template for cellular activities to repair, rebuild and regenerate damaged or lost tissues. While there are several biomaterials to select as three-dimensional scaffolds, it is generally agreed that a biomaterial to be used in tissue engineering needs to possess certain material characteristics such as biocompatibility, suitable surface chemistry, interconnected porosity, desired mechanical properties and biodegradability. The use of naturally derived polymers as three-dimensional scaffolds has been gaining widespread attention owing to their favourable attributes of biocompatibility, low cost and ease of processing. This paper discusses the synthesis of various polysaccharide-based, naturally derived polymers, and the potential of using these biomaterials to serve as tissue engineering three-dimensional scaffolds is also evaluated. In this study, naturally derived polymers, specifically cellulose, chitosan, alginate and agarose, and their composites, are examined. Single-component scaffolds of plain cellulose, plain chitosan and plain alginate as well as composite scaffolds of cellulose-alginate, cellulose-agarose, cellulose-chitosan, chitosan-alginate and chitosan-agarose are synthesized, and their suitability as tissue engineering scaffolds is assessed. It is shown that naturally derived polymers in the form of hydrogels can be synthesized, and the lyophilization technique is used to synthesize various composites comprising these natural polymers. The composite scaffolds appear to be sponge-like after lyophilization. Scanning electron microscopy is used to demonstrate the formation of an interconnected porous network within the polymeric scaffold following lyophilization. It is also established that HeLa cells attach and proliferate well on scaffolds of cellulose, chitosan or alginate. The synthesis protocols reported in this study can therefore be used to manufacture naturally derived polymer-based scaffolds as potential biomaterials for various tissue engineering applications. PMID- 20308113 TI - Next-generation biomedical implants using additive manufacturing of complex, cellular and functional mesh arrays. AB - In this paper, we examine prospects for the manufacture of patient-specific biomedical implants replacing hard tissues (bone), particularly knee and hip stems and large bone (femoral) intramedullary rods, using additive manufacturing (AM) by electron beam melting (EBM). Of particular interest is the fabrication of complex functional (biocompatible) mesh arrays. Mesh elements or unit cells can be divided into different regions in order to use different cell designs in different areas of the component to produce various or continually varying (functionally graded) mesh densities. Numerous design elements have been used to fabricate prototypes by AM using EBM of Ti-6Al-4V powders, where the densities have been compared with the elastic (Young) moduli determined by resonant frequency and damping analysis. Density optimization at the bone-implant interface can allow for bone ingrowth and cementless implant components. Computerized tomography (CT) scans of metal (aluminium alloy) foam have also allowed for the building of Ti-6Al-4V foams by embedding the digital-layered scans in computer-aided design or software models for EBM. Variations in mesh complexity and especially strut (or truss) dimensions alter the cooling and solidification rate, which alters the alpha-phase (hexagonal close-packed) microstructure by creating mixtures of alpha/alpha' (martensite) observed by optical and electron metallography. Microindentation hardness measurements are characteristic of these microstructures and microstructure mixtures (alpha/alpha') and sizes. PMID- 20308115 TI - Biomimetic hydroxyapatite-containing composite nanofibrous substrates for bone tissue engineering. AB - The fracture of bones and large bone defects owing to various traumas or natural ageing is a typical type of tissue malfunction. Surgical treatment frequently requires implantation of a temporary or permanent prosthesis, which is still a challenge for orthopaedic surgeons, especially in the case of large bone defects. Mimicking nanotopography of natural extracellular matrix (ECM) is advantageous for the successful regeneration of damaged tissues or organs. Electrospun nanofibre-based synthetic and natural polymer scaffolds are being explored as a scaffold similar to natural ECM for tissue engineering applications. Nanostructured materials are smaller in size falling, in the 1-100 nm range, and have specific properties and functions related to the size of the natural materials (e.g. hydroxyapatite (HA)). The development of nanofibres with nano-HA has enhanced the scope of fabricating scaffolds to mimic the architecture of natural bone tissue. Nanofibrous substrates supporting adhesion, proliferation, differentiation of cells and HA induce the cells to secrete ECM for mineralization to form bone in bone tissue engineering. Our laboratory (NUSNNI, NUS) has been fabricating a variety of synthetic and natural polymer-based nanofibrous substrates and synthesizing HA for blending and spraying on nanofibres for generating artificial ECM for bone tissue regeneration. The present review is intended to direct the reader's attention to the important subjects of synthetic and natural polymers with HA for bone tissue engineering. PMID- 20308114 TI - Atomic layer deposition-based functionalization of materials for medical and environmental health applications. AB - Nanoporous alumina membranes exhibit high pore densities, well-controlled and uniform pore sizes, as well as straight pores. Owing to these unusual properties, nanoporous alumina membranes are currently being considered for use in implantable sensor membranes and water purification membranes. Atomic layer deposition is a thin-film growth process that may be used to modify the pore size in a nanoporous alumina membrane while retaining a narrow pore distribution. In addition, films deposited by means of atomic layer deposition may impart improved biological functionality to nanoporous alumina membranes. In this study, zinc oxide coatings and platinum coatings were deposited on nanoporous alumina membranes by means of atomic layer deposition. PEGylated nanoporous alumina membranes were prepared by self-assembly of 1-mercaptoundec-11-yl hexa(ethylene glycol) on platinum-coated nanoporous alumina membranes. The pores of the PEGylated nanoporous alumina membranes remained free of fouling after exposure to human platelet-rich plasma; protein adsorption, fibrin networks and platelet aggregation were not observed on the coated membrane surface. Zinc oxide-coated nanoporous alumina membranes demonstrated activity against two waterborne pathogens, Escherichia coli and Staphylococcus aureus. The results of this work indicate that nanoporous alumina membranes may be modified using atomic layer deposition for use in a variety of medical and environmental health applications. PMID- 20308116 TI - Osteoblast adhesion, proliferation and growth on polyelectrolyte complex hydroxyapatite nanocomposites. AB - In this work, we have investigated osteoblast adhesion, proliferation and differentiation on nanocomposites of chitosan, polygalacturonic acid (PgA) and hydroxyapatite. These studies were done on both two- and three-dimensional (scaffold) samples. Atomic force microscopy experiments showed nanostructuring of film samples. Scaffolds were prepared by freeze-drying methods. The mechanical response and porosity of the scaffolds were also determined. The compressive elastic modulus and compressive strength were determined to be around 0.9 and 0.023 MPa, respectively, and the porosity of these scaffolds was found to be around 97 per cent. Human osteoblast cells were used to study their adhesion, proliferation and differentiation. Optical images were collected after different intervals of time of seeding cells. This study indicated that chitosan/PgA/hydroxyapatite nanocomposite films and scaffolds promote cellular adhesion, proliferation and differentiation. The formation of bone-like nodules was observed after 7 days of seeding cells. The nodule size continues to increase with time, and after 20 days the size of some nodules was around 735 microm. Scanning electron microscope images of nodules showed the presence of extracellular matrix. The alizarin red S staining technique was used to confirm mineralization of these nodules. PMID- 20308117 TI - Biomaterials by freeze casting. AB - The functional requirements for synthetic tissue substitutes appear deceptively simple: they should provide a porous matrix with interconnecting porosity and surface properties that promote rapid tissue ingrowth; at the same time, they should possess sufficient stiffness, strength and toughness to prevent crushing under physiological loads until full integration and healing are reached. Despite extensive efforts and first encouraging results, current biomaterials for tissue regeneration tend to suffer common limitations: insufficient tissue-material interaction and an inherent lack of strength and toughness associated with porosity. The challenge persists to synthesize materials that mimic both structure and mechanical performance of the natural tissue and permit strong tissue-implant interfaces to be formed. In the case of bone substitute materials, for example, the goal is to engineer high-performance composites with effective properties that, similar to natural mineralized tissue, exceed by orders of magnitude the properties of its constituents. It is still difficult with current technology to emulate in synthetic biomaterials multi-level hierarchical composite structures that are thought to be the origin of the observed mechanical property amplification in biological materials. Freeze casting permits to manufacture such complex, hybrid materials through excellent control of structural and mechanical properties. As a processing technique for the manufacture of biomaterials, freeze casting therefore has great promise. PMID- 20308118 TI - Biologically active collagen-based scaffolds: advances in processing and characterization. AB - A small number of type I collagen-glycosaminoglycan scaffolds (collagen-GAG scaffolds; CGSs) have unusual biological activity consisting primarily in inducing partial regeneration of organs in the adult mammal. Two of these are currently in use in a variety of clinical settings. CGSs appear to induce regeneration by blocking the adult healing response, following trauma, consisting of wound contraction and scar formation. Several structural determinants of biological activity have been identified, including ligands for binding of fibroblasts to the collagen surface, the mean pore size (which affects ligand density) and the degradation rate (which affects the duration of the wound contraction-blocking activity by the scaffold). Processing variables that affect these determinants include the kinetics of swelling of collagen fibres in acetic acid, freezing of the collagen-GAG suspension and cross-linking of the freeze dried scaffold. Recent developments in the processing of CGSs include fabrication of scaffolds that are paucidisperse in pore size, scaffolds with gradients in physicochemical properties (and therefore biological activity) and scaffolds that incorporate a mineral component. Advances in the characterization of the pore structure of CGSs have been made using confocal and nonlinear optical microscopy (NLOM). The mechanical behaviour of CGSs, as well as the resistance to degradative enzymes, have been studied. Following seeding with cells (typically fibroblasts), contractile forces in the range 26-450 nN per cell are generated by the cells, leading to buckling of scaffold struts. Ongoing studies of cell-seeded CGSs with NLOM have shown an advantage over the use of confocal microscopy due to the ability of the former method to image the CGS surfaces without staining (which alters its surface ligands), reduced cell photodamage, reduced fluorophore photobleaching and the ability to image deeper inside the scaffold. PMID- 20308119 TI - Infliximab may be effective in the treatment of steroid-resistant eosinophilic fasciitis: report of three cases. AB - OBJECTIVE: EF is a rare fibrosing disorder that may involve skin and internal organs. Current therapies include moderate- to high-dose glucocorticoids with or without use of immunosuppressives. METHODS: We report three cases of steroid resistant EF in clinical practice who were treated with 3 mg/kg every 8 weeks infliximab therapy. RESULTS: All patients noticed an improvement in their symptoms, joint contractures and skin thickening within 8 weeks of starting infliximab therapy, ultimately leading to a drug-free remission (range 1-3 years). CONCLUSION: Based on this and other reported cases, infliximab may be beneficial in patients with steroid-resistant EF. PMID- 20308120 TI - BSR and BHPR rheumatoid arthritis guidelines on eligibility criteria for the first biological therapy. PMID- 20308121 TI - BSR and BHPR rheumatoid arthritis guidelines on eligibility criteria for the first biological therapy. PMID- 20308122 TI - Sleepiness or fatigue? Can we detect treatable causes of tiredness in primary Sjogren's syndrome? AB - OBJECTIVE: To study the prevalence of fatigue and daytime sleepiness in primary SS (pSS) and analyse predicting sleep disturbing factors and other potential determinants of fatigue and sleepiness. METHOD: Seventy-two consecutive pSS patients and 59 age-matched healthy controls were compared. Assessment instruments were profile of fatigue (ProF), visual analogue scale fatigue, Epworth Sleepiness Scale (ESS), Hospital Anxiety and Depression Scale, restless legs syndrome (RLS) Diagnostic Criteria and Lund University Sleep Questionnaire. In addition, markers of immune disturbance, inflammation and disease activity using the European League Against Rheumatism SS Disease Activity Index were analysed in patients. RESULTS: Fatigue, especially somatic fatigue, is the main problem for pSS patients. Sleepiness is a minor problem. Patients had significantly more often anxiety, nocturia and woke up more frequently during the night than controls. The factors that predicted daytime fatigue in pSS patients were anxiety and nightly awakenings due to pain. Nocturia was frequent but was not associated with fatigue or sleepiness. RLS, depression and sicca symptoms contributed to fatigue in the univariate regression analysis only. CONCLUSIONS: This is the first study demonstrating not only the presence of disturbed sleep, but also that nightly musculoskeletal pain and other sleep disturbing factors and anxiety significantly influence fatigue. Management strategies aimed at these aspects should therefore be included in future trials for treatment of fatigue in pSS. PMID- 20308123 TI - Abstracts of the British Society for Rheumatology Annual Meeting and the British Health Professionals in Rheumatology Meeting. Birmingham, United Kingdom. April 21-23, 2010. PMID- 20308160 TI - Analytical approaches to RNA profiling data for the identification of genes enriched in specific cells. AB - We have recently developed a novel method for the affinity purification of the complete suite of translating mRNA from genetically labeled cell populations. This method permits comprehensive quantitative comparisons of the genes employed by each specific cell type. We provide a detailed description of tools for analysis of data generated with this and related methodologies. An essential question that arises from these data is how to identify those genes that are enriched in each cell type relative to all others. Genes relatively specifically employed by a cell type may contribute to the unique functions of that cell, and thus may become useful targets for development of pharmacological tools for cell specific manipulations. We describe here a novel statistic, the specificity index, which can be used for comparative quantitative analysis to identify genes enriched in specific cell populations across a large number of profiles. This measure correctly predicts in situ hybridization patterns for many cell types. We apply this measure to a large survey of CNS cell-specific microarray data to identify those genes that are significantly enriched in each population Data and algorithms are available online (www.bactrap.org). PMID- 20308161 TI - Synthesis of high-quality libraries of long (150mer) oligonucleotides by a novel depurination controlled process. AB - We have achieved the ability to synthesize thousands of unique, long oligonucleotides (150mers) in fmol amounts using parallel synthesis of DNA on microarrays. The sequence accuracy of the oligonucleotides in such large-scale syntheses has been limited by the yields and side reactions of the DNA synthesis process used. While there has been significant demand for libraries of long oligos (150mer and more), the yields in conventional DNA synthesis and the associated side reactions have previously limited the availability of oligonucleotide pools to lengths <100 nt. Using novel array based depurination assays, we show that the depurination side reaction is the limiting factor for the synthesis of libraries of long oligonucleotides on Agilent Technologies' SurePrint DNA microarray platform. We also demonstrate how depurination can be controlled and reduced by a novel detritylation process to enable the synthesis of high quality, long (150mer) oligonucleotide libraries and we report the characterization of synthesis efficiency for such libraries. Oligonucleotide libraries prepared with this method have changed the economics and availability of several existing applications (e.g. targeted resequencing, preparation of shRNA libraries, site-directed mutagenesis), and have the potential to enable even more novel applications (e.g. high-complexity synthetic biology). PMID- 20308162 TI - A rationally designed peptide enhances homologous recombination in vitro and resistance to DNA damaging agents in vivo. AB - The RecA family of proteins is essential in homologous recombination, a critical step in DNA repair. Here, we report that a rationally-designed small peptide based on the crystal structure of Escherichia coli RecA-DNA complex can promote homologous recombination through the enhancement of both RecA-mediated strand assimilation and three-strand exchange activity. Among 17 peptides tested, peptide #3 with the amino acid sequence of IRFLTARRR has the most potent activity in promoting the RecA-mediated D-loop formation by approximately 7.2-fold at 37 degrees C. Other peptides such as IRFLTAKKK and IRLLTARRR also have similar, albeit lower, activities. Therefore, hydrophobicity and poly-positive charges, and the space between them in those small peptides are crucial features for such activities. The enhancement of recombination by these peptides appears to be a general phenomenon as similar results were seen by using different plasmids. Remarkably, peptide #3 alone without RecA can also promote the D-loop formation at elevated temperature. Cell viability assays showed that the peptide elevates mammalian cell resistance to two cytotoxic DNA drugs, cisplatin and doxorubicin. The rescue of viability may result from increased DNA repair efficiency. Such peptides may find future biological applications. PMID- 20308163 TI - Integration of stable extracellular DNA released from Escherichia coli into the Bacillus subtilis genome vector by culture mix method. AB - The stable cloning of giant DNA is a necessary process in the production of recombinant/synthetic genomes. Handling DNA molecules in test tubes becomes increasingly difficult as their size increases, particularly above 100 kb. The need to prepare such large DNA molecules in a regular manner has limited giant DNA cloning to certain laboratories. Recently, we found stable plasmid DNA of up to 100 kb in Escherichia coli culture medium during the infection and propagation of lambda phage. The extracellular plasmid DNA (excpDNA) released from lysed E. coli was demonstrably stable enough to be taken up by competent Bacillus subtilis also present in the medium. ExcpDNA transfer, induced by simply mixing E. coli lysate with recipient B. subtilis, required no biochemical purification of the DNA. Here, this simple protocol was used to integrate excpDNA into a B. subtilis genome, designated the 'BGM vector'. A slightly modified protocol for DNA cloning in BGM is presented for DNA fragments >100 kb. This technique should facilitate giant DNA cloning in the BGM vector and allow its application to other hosts that can undergo natural transformation. PMID- 20308164 TI - Quantitative profiling of the full APOBEC3 mRNA repertoire in lymphocytes and tissues: implications for HIV-1 restriction. AB - The human APOBEC3 proteins are DNA cytidine deaminases that impede the replication of many different transposons and viruses. The genes that encode APOBEC3A, APOBEC3B, APOBEC3C, APOBEC3D, APOBEC3F, APOBEC3G and APOBEC3H were generated through relatively recent recombination events. The resulting high degree of inter-relatedness has complicated the development of specific quantitative PCR assays for these genes despite considerable interest in understanding their expression profiles. Here, we describe a set of quantitative PCR assays that specifically measures the mRNA levels of each APOBEC3 gene. The specificity and sensitivity of each assay was validated using a full matrix of APOBEC3 cDNA templates. The assays were used to quantify the APOBEC3 repertoire in multiple human T-cell lines, bulk leukocytes and leukocyte subsets, and 20 different human tissues. The data demonstrate that multiple APOBEC3 genes are expressed constitutively in most types of cells and tissues, and that distinct APOBEC3 genes are induced upon T-cell activation and interferon treatment. These data help define the APOBEC3 repertoire relevant to HIV-1 restriction in T cells, and they suggest a general model in which multiple APOBEC3 proteins function together to provide a constitutive barrier to foreign genetic elements, which can be fortified by transcriptional induction. PMID- 20308165 TI - Spontaneous aortic arch thrombus presenting as acute critical limb ischemia. AB - We report a case of a 52-year-old male who presented with acute leg ischemia and underwent successful femoral embolectomy and fasciotomies. Investigations revealed a pedunculated mass in the aortic arch, floating under the innominate and left common carotid arteries. Urgent resection was performed through a longitudinal aortotomy with deep hypothermic circulatory arrest and axillary artery perfusion to reveal a 2.5 x 1.5 cm pedunculated mass attached to the posterior aspect of the arch that was resected. Histology revealed thrombus material prompting lifelong systemic anticoagulation. On 3 months follow-up, the patient had returned to normal activities and computed tomography confirmed complete resection without recurrence. This case study demonstrates that spontaneous thrombus formation is possible in high-flow vascular regions such as the aortic arch and also confirms the importance of evaluating central sources of thromboemboli in patients presenting with acute limb ischemia. Urgent surgical removal is recommended and can be performed safely. PMID- 20308166 TI - A study of patient satisfaction following endothermal ablation for varicose veins. AB - OBJECTIVE: To evaluate patient satisfaction following endothermal ablation for varicose veins (VVs). METHODS: A 12-question survey was sent to consecutive patients treated with endothermal ablation--questions related to preprocedure symptoms, recurrence, further treatments, and patient satisfaction. RESULTS: Questionnaires sent a median 12 (range 6-22) months postintervention were returned by 177 (60.0%) of 295 patients; 63 (35.6%) of 177 received treatment for recurrent VVs. Preintervention symptoms included aching (141 [79.7%] of 177), swelling (86 [48.6%] of 177), and heaviness (72 [40.7%] of 177). Improvements in preoperative symptoms were reported by 82.5% (146 of 177). Postintervention recurrence was reported by 87 (49.4%) of 177; 61 (70.1%) of 87 reported a few recurrent varicosities only. Further treatment was required by 11 (6.2%) of 177; 79 (44.6%) of 177 of patients reported no complications. The majority (151 [85.8%] of 176) were satisfied with their treatment. In all, 16 (25.4%) of 62 of patients treated for recurrent VVs were dissatisfied versus 9 (7.9%) of 114 of those with primary VVs (P = .0026). CONCLUSIONS: The majority of patients are satisfied with results following endothermal ablation. Dissatisfaction may be more likely following treatment for recurrent VVs. PMID- 20308167 TI - An evaluation of the use of carbon dioxide angiography in endovascular aortic aneurysm repair. AB - INTRODUCTION: Renal dysfunction after endovascular aortic aneurysm repair is an increasingly recognised problem. Carbon dioxide (CO(2)) angiography has been used to limit the risk of contrast nephrotoxicity during endovascular procedures. This prospective study evaluates the performance of CO(2) angiography during EVAR. METHODS: Seventeen patients undergoing EVAR over a 12 month period were included. All were males with a median age of 74 (range 62-86) years. The median preoperative creatinine was 105 (range 77-165) micromol/L. CO(2) angiography was used routinely in all patients for graft positioning. Contrast was used for completion angiograms and whenever CO(2) did not satisfactorily demonstrate the anatomy. RESULTS: All patients had successful deployment of stent graft. The median contrast usage was 59 (range 20-250)ml. CO( 2) angiography successfully demonstrated the aortic and iliac bifurcation in all 17 cases and the renal artery anatomy in 9. 7 out of 17 patients had both CO(2) and contrast completion angiography. CO(2) correlated with contrast angiography in 6 of the 7 patients. There was no significant difference in pre and post-operative creatinine values (P >0.9; Wilcoxon test). CONCLUSION: CO(2) angiography is a useful adjunct to contrast during the performance of EVAR and helps reduce contrast load and the risk of contrast nephrotoxicity. PMID- 20308168 TI - Anesthetic experience with endovascular aortic aneurysm repair. AB - BACKGROUND: We endeavored to characterize the anesthesia experience with endovascular aneurysm repair (EVAR) at a large academic medical center in the United States. METHODS: A retrospective review of electronic medical records was conducted for all patients undergoing elective EVAR from 2002 to 2007 in a large academic medical center. RESULTS: A total of 522 cases met inclusion criteria, with 4% of cases using general anesthesia (GA), 92% regional anesthesia (RA), and 4% local anesthesia (LA). There was no statistically significant difference between the groups for duration of surgery or in-hospital mortality. In-hospital length of stay was longer for GA than LA or RA. Four cases were converted to open repair. Two mortalities occurred during the perioperative period (0.4% of cases). CONCLUSIONS: The vast majority of EVAR were successfully performed under RA, involved mild blood loss, involved infrequent need for conversion to GA, and resulted in brief in-hospital length of stay and low mortality rate. PMID- 20308169 TI - A prospective, randomized, placebo-controlled study evaluating the efficacy of dexmedetomidine for sedation during vascular procedures. AB - OBJECTIVE: To examine the efficacy of dexmedetomidine (DEX) as a primary sedative during vascular procedures performed under monitored anesthesia care (MAC). A total of 55 patients were randomized in a 2:2:1 ratio to receive either DEX 1.0 microg/kg load or DEX 0.5 microg/kg load versus midazolam (MDZ) boluses, the current standard of care. This was followed by a maintenance infusion of DEX versus a normal saline infusion for the control group. Midazolam was given in 0.5 mg increments to maintain an equivalent target level of sedation among the 3 study groups. Fentanyl was given in 25 microg increments to treat pain as needed. The percentage of DEX patients not requiring MDZ and the total dose of MDZ and fentanyl were compared to the control. Dexmedetomidine was efficacious as a sole sedative for 50% of patients. The total dose of MDZ and fentanyl was significantly less during the DEX infusions. Patient satisfaction was superior with DEX. PMID- 20308170 TI - The diagnosis and management of aortic dissection. AB - Aortic dissection represents the most common aortic emergency, affecting 3 to 4 per 100,000 people per year and is still associated with a high mortality. Twenty percent of the patients with aortic dissection die before reaching hospital and 30% die during hospital admission. Aortic dissections may be classified in 3 ways: according to their anatomical extent (the Stanford or DeBakey systems), according to the time from onset (acute or chronic), and according to the underlying pathology (the European Society of Cardiologists' system). Advances in endovascular technology have provided new treatment options. Hybrid endovascular and conventional open surgical repair represent the mainstay of treatment for acute type A dissection. Medical management remains the gold standard for acute and uncomplicated chronic type B dissection, though endovascular surgery offers exciting potential in the management of complicated type B dissection through sealing of the intimal entry tear. PMID- 20308171 TI - Outcome in patients requiring renal replacement therapy after open surgical repair for ruptured abdominal aortic aneurysm. AB - OBJECTIVE: To determine the relationship between postoperative renal replacement therapy (RRT) and patient survival after open surgical repair (OR) of ruptured abdominal aortic aneurysm (rAAA). METHODS: A retrospective review of consecutive patients who underwent OR for rAAA repair between January 2002 and July 2008 was performed. Early (<30 days) and late (>30 days) outcomes were assessed. RESULTS: A total of 94 patients (69 men; median [range] age 73.8 [56-89] years) underwent OR of rAAA (infrarenal = 78, juxtarenal = 15, and suprarenal = 1). In-hospital mortality rate was 40% and mean (range) length of intensive care unit (ICU) stay was 9.3 (0-56) days. A total of 23 (24%) patients required postoperative RRT. In hospital mortality rate was significantly higher (RRT: 87% (20 of 23) vs no RRT: 18 of 71 (25%), P < .0001) and ICU stay significantly longer (RRT: mean (range) days; 14.8 (1-44) vs no RRT: 7.5 (0-56), P = .04) in the RRT patients. On multivariate analysis, RRT (P = .0053) and/or inotropic support (P = .0033) were independent risk factors for death within 30 days of the index procedure. CONCLUSIONS: Renal replacement therapy following OR of rAAA is an independent risk factor for mortality. PMID- 20308172 TI - Postdischarge outcomes of blunt cerebrovascular injuries. AB - A retrospective review was conducted to assess outcomes of blunt cerebrovascular injuries (BCVIs) diagnosed in a 14-month period at a level-1 trauma center and evaluated postdischarge at a single vascular practice. Twenty-nine patients with 34 BCVIs (10 carotid; 24 vertebral) were admitted. Eleven (37.9%) patients were treated with combined anticoagulation and antiplatelet therapy, 9 (31.0%) with anticoagulation, and 4 (13.8%) with antiplatelets. Five (17.2%) patients underwent observation. Seventeen (58.6%) patients (19 injuries) returned for follow-up evaluation. At a mean follow-up of 9.2 weeks, all patients had normal neurological examinations with no complications. Sixteen (84.2%) BCVIs resolved. Anticoagulation and antiplatelet therapies were equally effective in preventing cerebral infarction. Although the majority of lesions resolve, BCVIs have the ability to progress and often require surgical intervention. Routine follow-up after discharge is warranted for all BCVIs and should include repeat computed tomography angiography (CTA) with bilateral carotid/vertebral duplex ultrasound (US) as a physiological test. PMID- 20308173 TI - Double microcatheter single vascular access embolization technique for complex peripheral vascular pathology. AB - The authors describe an embolization technique that allows safe, controllable exclusion of complex vascular pathologies using a single vascular access and 2 microcatheters. This technique is particularly useful in situations where high flow increases the risk of coil migration and nontarget embolization and in large aneurysms. It affords precise placement and repositioning of coils. This method was used to treat patients with pulmonary arteriovenous malformations, renal arteriovenous fistulae and aneurysms, visceral arterial aneurysms and pseudoaneurysms, an aortic pseudoaneurysm, and occlusion of native parent vessels. The technique facilitated safe and successful endovascular closure in all cases. PMID- 20308175 TI - Abdominal aortic aneurysms in triplets. AB - We report the case of 3 male triplets, 2 of whom, both lifelong smokers, presented with ruptured abdominal aortic aneurysm (AAA) within 24 hours of each other. One survived surgery but the other died from the rupture. The third brother, an ex-smoker, was found to have an ectatic aorta and was placed into a surveillance program. This case highlights and discusses the combination of genetic and environmental factors that underpin the etiology of aneurysms and demonstrates the importance of assessing first-degree relatives of patients presenting with AAA. PMID- 20308174 TI - Contrast-enhanced magnetic resonance angiography following subintimal recanalization. AB - PURPOSE: To describe the appearance of lower extremity runoff vessels following subintimal recanalization (SIR) on contrast-enhanced magnetic resonance angiography (ceMRA) and compare 2 different ceMRA techniques. METHODS: A total of 6 patients underwent stepping table 3-dimensional (3D) ceMRA and time-resolved 2 dimensional (2D) MRA within 1 to 3 days (mean 1.83 days) following SIR. The 2 techniques were compared with intra-arterial digital subtraction angiography (DSA). RESULTS: A total of 15 arteries were recanalized in 6 patients. Three dimensional ceMRA allowed evaluation of patency in all segments above the knee. Postprocedural hyperemia impaired the assessment of the trifurcation vessels on 3D ceMRA. Due to its higher temporal resolution 2D MRA was not affected by venous contamination and allowed reliable confirmation of patency of the recanalized vessels. CONCLUSIONS: Diagnostic MRA studies of the lower extremity runoff vessels following SIR is possible, but a hybrid technique using a stepping table MR DSA and a time-resolved sequence like 2D MRA of the calf station is necessary for runoff assessment. PMID- 20308176 TI - Endovascular management of congenital atresia of the infrarenal IVC. AB - This case illustrates the feasibility of endovascular treatment for chronic venous insufficiency attributable to congenital atresia of the infrarenal inferior vena cava (IVC). Three-dimensional computed tomography (CT) venography can elucidate alternate sites of drainage and identify other venous pathology, such as dominant stenoses that may be amenable to venoplasty and/or stent placement. PMID- 20308177 TI - varLD: a program for quantifying variation in linkage disequilibrium patterns between populations. AB - MOTIVATION: Linkage disequilibrium (LD) differences between populations can potentially result in failure to replicate primary signals of trait association in independent genome-wide association studies (GWAS). However, such inter population LD differences can be leveraged to narrow the search for common causal variants responsible for the association signals observed. The ability to assess and quantify LD variations among populations is thus expected to contribute to both replication and fine-mapping stages of GWAS. AVAILABILITY: The program varLD is available for download from http://www.nus-cme.org.sg/software/varld.html. PMID- 20308179 TI - Latest tuberculosis statistics are a "wake-up call for all governments to act immediately". PMID- 20308182 TI - Sexual health consultation for men who have sex with men. PMID- 20308183 TI - Patent on BRCA1 gene should never have been granted, researchers say. PMID- 20308186 TI - Global Fund will eliminate vertical transmission of HIV by 2015 if funding continues at present level, report says. PMID- 20308188 TI - Health payment-induced poverty under China's New Cooperative Medical Scheme in rural Shandong. AB - OBJECTIVE: To measure the incidence and severity of health payment-induced poverty of rural households under the New Cooperative Medical Scheme (NCMS) in rural Shandong, China. METHOD: We collected primary data from a household survey to identify catastrophic health payments and measure associated health payment induced poverty in a county of Shandong province. From a stratified random cluster sample of 3101 households, 375 households that might be at risk of catastrophic payments were identified and interviewed. A validity test of the screening method was conducted, from which we obtained the adjusted total number of households with catastrophic payments in the sample of 3101. The health payment-induced poverty incidence and severity were compared without and with NCMS reimbursements. RESULTS: Before the NCMS intervention, 5.06% of the sample households fell below the national poverty line due to health payments in 2004, compared with 4.03% after reimbursements. With NCMS reimbursements, the health payment-induced poverty gap of those households still remaining below the Chinese national poverty line dropped by 19.2% to an average of 977.2 Yuan. CONCLUSION: Out-of-pocket health payments remain a severe burden for rural households. Financial protection from the NCMS was limited. PMID- 20308190 TI - A comparison of two assessment systems in predicting functional outcomes of older rehabilitation patients. PMID- 20308191 TI - Intracoronary infusion of selected autologous bone marrow stem cells improves longitudinal myocardial strain and strain rate in patients with old anterior myocardial infarction without recent revascularization. AB - AIMS: We sought to evaluate the efficacy of intracoronary infusion of selected bone marrow stem cells (BMSCs) in patients with remote, anterior non-viable MI by the use of tissue Doppler imaging. METHODS AND RESULTS: We infused selected CD133+ and CD133-CD34+ BMSCs in 10 patients enrolled in the study. Peak systolic strain rate, maximum strain during the cardiac cycle (epsilon(max)), strain during ejection time (epsilon(et)), and post-systolic strain (epsilon(ps)) were measured. Peak systolic strain rate (-0.69 +/- 0.2 vs. -1.15 +/- 0.27, P = 0.001), epsilon(max) (-9.87 +/- 3.30 vs. -15.57 +/- 5, P = 0.006), and epsilon(et) (-7.45+/-2.86 vs. -10.92 +/- 4.45, P = 0.015) improved significantly during the rest study 6 months after cell infusion. Low-dose inotropic challenge also showed significant improvement of longitudinal deformation indices in the follow-up study. Global ejection fraction did not improve significantly after cell therapy. CONCLUSION: Intracoronary infusion of selected BMSCs in patients with remote, anterior, non-viable myocardial infarction is safe and leads to improvement of longitudinal deformation indices 6 months after the infusion. PMID- 20308189 TI - Identification and characterization of beta-lactamase inhibitor protein-II (BLIP II) interactions with beta-lactamases using phage display. AB - Protein-protein interactions are critical to cellular processes yet the ability to predict and rationally design interactions is limited because of incomplete knowledge of the principles governing these interactions. The beta-lactamase inhibitory protein (BLIP)/beta-lactamase interaction has become a model system to investigate protein-protein interactions and has been the focus of several structural, thermodynamic and binding specificity studies. BLIP-II also inhibits beta-lactamase but has no sequence homology with BLIP. The structure of BLIP-II in complex with TEM-1 beta-lactamase revealed that BLIP-II has a completely different structure than BLIP but it interacts with the same protruding loop helix region of TEM-1 as does BLIP. The significance of the individual interacting residues in molecular recognition by BLIP-II is currently unknown. Therefore, a phage display vector was developed with the purpose of expressing BLIP-II onto the surface of the M13 filamentous bacteriophage. The BLIP-II displayed phage bound to TEM-1 with picomolar affinity indicating that BLIP-II is properly folded while on the surface of the phage. The phage system, as well as enzyme inhibition assays with purified proteins, revealed that BLIP-II is a more potent inhibitor than BLIP for several class A beta-lactamases with K(i) values in the low picomolar range. PMID- 20308192 TI - How to measure the effects of the intracoronary stem cell therapy? AB - The results of clinical studies showed that there is a moderate increase in left ventricular (LV) ejection fraction (EF) at 4-6 months after stem cell therapy. So far, the endpoint of such trials was the change of LVEF and volumes measured by LV angiography or MRI; however, these parameters might not be optimal to assess the effects of BMC therapy. BOOST trial was one of the first studies addressing the effect of bone marrow cell transfer in patients with acute ST-elevation myocardial infarction. The results of 5-year follow-up were reported, showed no sustained effect on the LV systolic function in the whole group, but some beneficial effects on diastolic function were found. Other study showed using tissue-Doppler that after implantation of selected CD133+ and CD133-CD34+ bone marrow-derived cells in patients with history of anterior MI and severely reduced LVEF the indices of regional LV systolic function improved. Clinical significance of these findings remains to be established; however, the assessment of diastolic function and tissue-Doppler imaging might be valuable parameters in stem cell based trials. PMID- 20308193 TI - Association between coronary flow reserve, left ventricular systolic function, and myocardial viability in acute myocardial infarction. AB - AIMS: To investigate the relationships between coronary flow reserve (CFR), left ventricular (LV) systolic function, and myocardial viability in patients with acute myocardial infarction (AMI). METHODS AND RESULTS: In 149 patients with a first AMI, we estimated CFR non-invasively and assessed LV systolic function with low-dose dobutamine Doppler echocardiography (LDDE), which also identified viability. Resting echocardiographic variables did not differ between patients with preserved (54.4%) and low CFR (45.6%). During LDDE, longitudinal LV function was decreased [9.5 cm/s (8;11.3) vs. 10.6 cm/s (8.5;12.5), P = 0.04] and end systolic volume increased [49.5 mL (38;66) vs. 42 (31;61), P = 0.04] in patients with low compared with preserved CFR. Among 87 (58%) patients with resting wall motion abnormalities, 28 met the criteria for viability. One of 53 (2%) met the criteria for viability in patients with CFR < or =2 compared with 27 of 34 (79%) with CFR > 2, P < 0.0001. CONCLUSION: Resting echocardiographic parameters were similar in patient groups. During LDDE, patients with reduced CFR had increased LV size and compromised longitudinal function of LV and were less likely to have evidence of myocardial viability. PMID- 20308194 TI - Anomalous origin of the left coronary artery from the pulmonary artery with patent ductus arteriosus: a must to recognize entity. AB - Anomalous left coronary artery from the pulmonary trunk (ALCAPA) presents in early infancy with a clinical picture of congestive heart failure with left ventricular (LV) dysfunction and mitral insufficiency. These manifestations of myocardial ischaemia may be masked in the presence of an associated patent ductus arteriosus (PDA) or ventricular septal defect (VSD) which prevents the fall of pulmonary artery pressures and allows perfusion of the anomalous coronary artery. We present a case of a patient with large PDA-associated ALCAPA and preserved LV function. The importance of such a finding lies in the fact that VSD closure or PDA ligation in such cases would unmask the ALCAPA. PMID- 20308195 TI - Overuse injuries in high school athletes. AB - PURPOSE: To evaluate relationships between seasonal patterns of athletic participation and overuse injuries in high school athletes. METHODS: Self reported survey of sports played and injuries sustained during the preceding 12 months administered anonymously to 9th-12th graders in school. RESULTS: Females suffered more overuse injuries than males. Overuse injuries increased slightly with age and with seasons of sports played per calendar year. Students who played sports all year long had 42% increased risk of overuse injury compared to those who played fewer than 4 seasons. CONCLUSIONS: Reducing the number of sport seasons played by high school athletes could decrease their rate of overuse injuries, with the greatest gains potentially achieved by taking at least one season off from sports entirely each calendar year. PMID- 20308196 TI - Vitiligo therapy in children: a case for considering excimer laser treatment. PMID- 20308197 TI - Healthy for now? A cross-sectional study of the comorbidities in obese preschool children in the United States. AB - OBJECTIVE: Examine health of preschoolers by BMI status. METHODS: A cross sectional analysis of children 3 to 5 years old in the 1999-2008 National Health and Nutrition Examination Survey was carried out. The measured age- and sex specific BMI percentiles were used to categorize children as very obese, obese, overweight, or healthy weight. The authors used logistic regression to examine the effect of weight status on 17 available measures of current child health potentially related to obesity. RESULTS: Except for very obese children, weight status had minimal effect on most measures of health for preschool-aged children (n = 2792). Parents of very obese children reported poorer general health and more activity limitations for their children. Additionally, very obese girls had more frequent/severe headaches, and overweight/obese boys had more asthma diagnoses. CONCLUSIONS: Only severe obesity appears consistently related to immediate health problems in preschool-aged children. Parental perception that very obese children have worse health and more activity limitations may lead to decreases in physical activity, which would perpetuate obesity. PMID- 20308198 TI - Oxytocin, dopamine, and the amygdala: a neurofunctional model of social cognitive deficits in schizophrenia. AB - Until recently, the social cognitive impairment in schizophrenia has been underappreciated and remains essentially untreated. Deficits in emotional processing, social perception and knowledge, theory of mind, and attributional bias may contribute to functional social cognitive impairments in schizophrenia. The amygdala has been implicated as a key component of social cognitive circuitry in both animal and human studies. In addition, structural and functional studies of schizophrenia reproducibly demonstrate abnormalities in the amygdala and dopaminergic signaling. Finally, the neurohormone oxytocin plays an important role in multiple social behaviors in several mammals, including humans. We propose a model of social cognitive dysfunction in schizophrenia and discuss its therapeutic implications. The model comprises abnormalities in oxytocinergic and dopaminergic signaling in the amygdala that result in impaired emotional salience processing with consequent social cognitive deficits. PMID- 20308199 TI - Relation of whole blood carboxyhemoglobin concentration to ambient carbon monoxide exposure estimated using regression. AB - Exposure to carbon monoxide (CO) and other ambient air pollutants is associated with adverse pregnancy outcomes. While there are several methods of estimating CO exposure, few have been evaluated against exposure biomarkers. The authors examined the relation between estimated CO exposure and blood carboxyhemoglobin concentration in 708 pregnant western Washington State women (1996-2004). Carboxyhemoglobin was measured in whole blood drawn around 13 weeks' gestation. CO exposure during the month of blood draw was estimated using a regression model containing predictor terms for year, month, street and population densities, and distance to the nearest major road. Year and month were the strongest predictors. Carboxyhemoglobin level was correlated with estimated CO exposure (rho = 0.22, 95% confidence interval (CI): 0.15, 0.29). After adjustment for covariates, each 10% increase in estimated exposure was associated with a 1.12% increase in median carboxyhemoglobin level (95% CI: 0.54, 1.69). This association remained after exclusion of 286 women who reported smoking or being exposed to secondhand smoke (rho = 0.24). In this subgroup, the median carboxyhemoglobin concentration increased 1.29% (95% CI: 0.67, 1.91) for each 10% increase in CO exposure. Monthly estimated CO exposure was moderately correlated with an exposure biomarker. These results support the validity of this regression model for estimating ambient CO exposures in this population and geographic setting. PMID- 20308200 TI - Root resorption before and after orthodontic treatment: a clinical study of contributory factors. AB - This clinical study evaluated factors related to root resorption before (T1) and after (T2) orthodontic treatment. Ninety-six subjects between 9 and 34 years (34 males and 62 females) who had been treated using fixed appliances for at least 1 year and who had panoramic radiographs at T1 and T2 were selected. The relationship between root resorption at T1 and T2, with regard to gender, age, extraction versus non-extraction patterns, specific teeth and treatment duration was investigated. No statistically significant differences in root resorption were found in relation to gender. Significant differences in root resorption (P = 0.000, P < 0.01) and also in treatment duration (P = 0.036, P < 0.05) were noted between the extraction and non-extraction groups; extraction and treatment duration correlated with T2 mean root resorption. Patient age correlated with root resorption of the upper incisors at T1 and T2. Using multiple regression analysis, age and duration of treatment were found to be more associated with root resorption than with extractions; the presence of root resorption at T1 was associated with T2 root resorption, especially of the anterior teeth. PMID- 20308201 TI - Dissociable roles of the medial prefrontal cortex and nucleus accumbens core in goal-directed actions for differential reward magnitude. AB - The medial prefrontal cortex (mPFC) and nucleus accumbens (NAc) are 2 structures within a larger corticolimbic network mediating goal-directed actions, especially when the procurement of different goals is sensitive to impulsive tendencies. The present study investigated the role of these structures in goal-directed action for differential reward by training rats to respond for sucrose reward at a nosepoke operandum such that longer duration nosepokes (up to 2 s) resulted in correspondingly larger volumes of reward. After 16 weeks of training, neurotoxic lesions of either the mPFC or the NAc-core were performed, followed by reassessment of sustained response behavior. Lesions of mPFC increased choice impulsivity by shifting responding away from large rewards toward rewards of smaller sizes. The total volume of reward earned remained unchanged, thereby dissociating the lesion effects on response parameters from overall motivation for reward. In contrast, NAc-core lesions decreased the total amount of responding and total volume of reward earned without altering choice impulsivity across differing nosepoke durations and reward sizes. These results suggest that the mPFC mediates the ability to maintain behavioral responding over longer durations for larger magnitude rewards, while the NAc-core mediates the initiation of responding, perhaps by affecting motivational drive, independent of reward magnitude. PMID- 20308202 TI - It was not MY fault: event-related brain potentials in active and observational learning from feedback. AB - Performance feedback during learning is accompanied by a negative event-related potentials (ERP) component, the feedback-related negativity (FRN), which codes a reward prediction error. An open issue relates to the coding of feedback stimuli in observational learning. The present study aimed to determine differences in the neural processing of feedback in active and observational learners in a between-subjects design. By choosing between different stimuli, 15 active learners could learn a rule determining the probability of monetary reward. Each of the 15 observers was yoked to the performance of one active learner. In test trials, observers could prove whether they had gained insight into the rule. Although both groups learned at a comparable rate, FRN amplitudes following negative feedback were significantly reduced in observational relative to active learners, whereas there was no difference for the FRN in response to positive feedback. Additionally, between-group differences were already observed in the time window preceding the FRN, between 150 and 220 ms after feedback onset. The processing of feedback stimuli thus depends upon the direct relevance for one's own action planning. The FRN as an error signal indicating the need for behavioral adaptation appears to be especially relevant, if negative feedback is linked to agency. PMID- 20308204 TI - Vasodilator-stimulated phosphoprotein: crucial for activation of Rac1 in endothelial barrier maintenance. PMID- 20308203 TI - Nociceptive afferent activity alters the SI RA neuron response to mechanical skin stimulation. AB - Procedures that reliably evoke cutaneous pain in humans (i.e., 5-7 s skin contact with a 47-51 degrees C probe, intradermal algogen injection) are shown to decrease the mean spike firing rate (MFR) and degree to which the rapidly adapting (RA) neurons in areas 3b/1 of squirrel monkey primary somatosensory cortex (SI) entrain to a 25-Hz stimulus to the receptive field center (RF(center)) when stimulus amplitude is "near-threshold" (i.e., 10-50 MUm). In contrast, RA neuron MFR and entrainment are either unaffected or enhanced by 47 51 degrees C contact or intradermal algogen injection when the amplitude of 25 Hz stimulation is 100-200 MUm (suprathreshold). The results are attributed to an "activity dependence" of gamma-aminobutyric acid (GABA) action on the GABA(A) receptors of RA neurons. The nociceptive afferent drive triggered by skin contact with a 47-51 degrees C probe or intradermal algogen is proposed to activate nociresponsive neurons in area 3a which, via corticocortical connections, leads to the release of GABA in areas 3b/1. It is hypothesized that GABA is hyperpolarizing/inhibitory and suppresses stimulus-evoked RA neuron MFR and entrainment whenever RA neuron activity is low (as when the RF(center) stimulus is weak/near-threshold) but is depolarizing/excitatory and augments MFR and entrainment when RA neuron activity is high (when the stimulus is strong/suprathreshold). PMID- 20308206 TI - Inflorescence development in petunia: through the maze of botanical terminology. AB - Flowering plants have developed many ways to arrange their flowers. A flower bearing branch or system of branches is called an inflorescence. The number of flowers that an inflorescence contains ranges from a single flower to endless flower-clusters. Over the past centuries, botanists have classified inflorescences based on their morphology, which has led to an unfortunate maze of complex botanical terminology. With the rise of molecular developmental biology, research has become increasingly focused on how inflorescences develop, rather than on their morphology. It is the decisions taken by groups of stem cells at the growing tips of shoots, called meristems, on when and where to produce a flower or a shoot that specify the course of inflorescence development. Modelling is a helpful aid to follow the consequences of these decisions for inflorescence development. The so-called transient model can produce the broad inflorescence types: cyme, raceme, and panicle, into which most inflorescences found in nature can be classified. The analysis of several inflorescence branching mutants has led to a solid understanding of cymose inflorescence development in petunia (Petunia hybrida). The cyme of petunia is a distinct body plan compared with the well-studied racemes of Arabidopsis and Antirrhinum, which provides an excellent opportunity to study evolutionary developmental biology (evo-devo) related questions. However, thus far, limited use has been made of this opportunity, which may, at least in part, be due to researchers getting lost in the terminology. Some general issues are discussed here, while focusing on inflorescence development in petunia. PMID- 20308205 TI - Differential expression of genes identified by suppression subtractive hybridization in petals of opening carnation flowers. AB - Flower opening is an event accompanied by morphological changes in petals which include elongation, expansion, and outward-curving. Petal cell growth is a fundamental process that underlies such phenomena, but its molecular mechanism remains largely unknown. Suppression subtractive hybridization was performed between petals during the early elongation period (stage 1) and during the opening period (stage 5) in carnation flowers and a pair of subtraction libraries abundant in differentially expressed genes was constructed at each stage. 393 cDNA clones picked up by differential screening out of 1728 clones were sequenced and 235 different cDNA fragments were identified, among which 211 did not match any known nucleotide sequence of carnation genes in the databases. BLASTX search of nucleotide sequences revealed that putative functions of the translational products can be classified into several categories including transcription, signalling, cell wall modification, lipid metabolism, and transport. Open reading frames of 15 selected genes were successfully determined by rapid amplification of cDNA ends (RACE). Time-course analysis of these genes by real-time RT-PCR showed that transcript levels of several genes correlatively fluctuate in petals of opening carnation flowers, suggesting an association with the morphological changes by elongation or curving. Based on the results, it is suggested that the growth of carnation petals is controlled by co-ordinated gene expression during the progress of flower opening. In addition, the possible roles of some key genes in the initiation of cell growth, the construction of the cell wall and cuticle, and transport across membranes were discussed. PMID- 20308207 TI - Malformations in a chornobyl-impacted region. AB - OBJECTIVE: One of the populations most exposed to chronic low-dose radiation from Chornobyl (Chernobyl in Russian) lives in Polissia, the region representing the northern half of Rivne Province (Oblast) in Ukraine. Here the patterns and population rates of malformations are reported and possible etiologic factors and regional contrasts are explored. PATIENTS AND METHODS: Malformations, as defined by international standards, noted among all 96 438 births in Rivne between 2000 and 2006, were analyzed statistically. Contrasts of rates in Polissia compared with the rest of Rivne also were investigated. RESULTS: The overall rate of neural tube defects in Rivne is among the highest in Europe (22.2 per 10,000 live births). The rates of conjoined twins and teratomas also seem to be elevated. In Polissia, the overall rates of neural tube defects are even higher (27.0 vs 18.3, respectively; odds ratio: 1.46 [95% confidence interval: 1.13-1.93]), and the rates of microcephaly and microphthalmia may also be elevated. CONCLUSIONS: The malformation patterns observed suggest early disruptions of blastogenesis, manifesting as alterations of body axes, twinning, duplications, laterality, and midline formation. The results are sufficiently compelling to justify continuing and expanding this investigation of malformations in chronic low-dose radiation impacted regions of Ukraine. PMID- 20308208 TI - Measles outbreak in a highly vaccinated population, San Diego, 2008: role of the intentionally undervaccinated. AB - OBJECTIVE: In January 2008, an intentionally unvaccinated 7-year-old boy who was unknowingly infected with measles returned from Switzerland, resulting in the largest outbreak in San Diego, California, since 1991. We investigated the outbreak with the objective of understanding the effect of intentional undervaccination on measles transmission and its potential threat to measles elimination. METHODS: We mapped vaccination-refusal rates according to school and school district, analyzed measles-transmission patterns, used discussion groups and network surveys to examine beliefs of parents who decline vaccination, and evaluated containment costs. RESULTS: The importation resulted in 839 exposed persons, 11 additional cases (all in unvaccinated children), and the hospitalization of an infant too young to be vaccinated. Two-dose vaccination coverage of 95%, absence of vaccine failure, and a vigorous outbreak response halted spread beyond the third generation, at a net public-sector cost of $10 376 per case. Although 75% of the cases were of persons who were intentionally unvaccinated, 48 children too young to be vaccinated were quarantined, at an average family cost of $775 per child. Substantial rates of intentional undervaccination occurred in public charter and private schools, as well as public schools in upper-socioeconomic areas. Vaccine refusal clustered geographically and the overall rate seemed to be rising. In discussion groups and survey responses, the majority of parents who declined vaccination for their children were concerned with vaccine adverse events. CONCLUSIONS: Despite high community vaccination coverage, measles outbreaks can occur among clusters of intentionally undervaccinated children, at major cost to public health agencies, medical systems, and families. Rising rates of intentional undervaccination can undermine measles elimination. PMID- 20308209 TI - Prevalence of complementary medicine use in pediatric cancer: a systematic review. AB - CONTEXT: Complementary and alternative medicine (CAM) is used by pediatric patients with cancer, but the actual frequency of CAM use is undetermined. OBJECTIVE: In this systematic review we summarize the current evidence on the prevalence of CAM use in pediatric patients with cancer and assess the reported quality of included studies. METHODS: We systematically searched 6 major electronic databases, reference lists of existing reviews, and personal files. We included full articles about primary research studies (without language restriction) that reported the prevalence of CAM use if all or a defined subsample of participants were pediatric patients with cancer. Detailed information regarding methods and results was extracted from the original articles. A quality-assessment tool was rigorously developed on the basis of the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement and used to assess reported study quality. Formal tests of interrater agreement were conducted. RESULTS: We included 28 studies with survey data (collected from 1975 to 2005) from 3526 children. In 20 studies with 2871 participants, the prevalence of any CAM use (since cancer diagnosis) ranged from 6% to 91%; considerable heterogeneity across studies precluded meta-analysis. Study quality was mixed and not correlated with CAM prevalence. Herbal remedies were the most popular CAM modality, followed by diets/nutrition and faith healing. Commonly reported reasons for CAM use included to help cure or fight the child's cancer, symptomatic relief, and support of ongoing use of conventional therapy. There was little evidence of an association between CAM use and patients' sociodemographic characteristics. CONCLUSIONS: Many pediatric patients with cancer use CAM. It is important that pediatricians be aware of this fact and encourage open communication with patients and their parents. Using standardized survey methods and CAM definitions in future studies could improve their quality and help generate comparable data. Our quality-assessment tool could prove valuable for other reviews of prevalence studies. PMID- 20308210 TI - Redefining the role of intestinal microbes in the pathogenesis of necrotizing enterocolitis. AB - Neonatal necrotizing enterocolitis (NEC) remains an important cause of morbidity and mortality among very low birth weight infants. It has long been suspected that intestinal microbes contribute to the pathogenesis of NEC, but the details of this relationship remain poorly understood. Recent advances in molecular biology and enteric microbiology have improved our ability to characterize intestinal microbes from infants with NEC and from healthy unaffected newborns. The lack of diversity within the neonatal intestine makes it possible to study gut microbial communities at a high level of resolution not currently possible in corresponding studies of the adult intestinal tract. Here, we summarize clinical and laboratory evidence that supports the hypothesis that NEC is a microbe mediated disorder. In addition, we detail recent technologic advances that may be harnessed to perform high-throughput, comprehensive studies of the gut microbes of very low birth weight infants. Methods for characterizing microbial genotype are discussed, as are methods of identifying patterns of gene expression, protein expression, and metabolite production. Application of these technologies to biological samples from affected and unaffected newborns may lead to advances in the care of infants who are at risk for the unabated problem of NEC. PMID- 20308211 TI - Effects of changing body-checking rules on rates of injury in minor hockey. AB - OBJECTIVE: In this study we explored the effects of the 2002 rule change in Ontario minor hockey, in which body-checking was introduced at the atom (ages 9 10) instead of the peewee (previously ages 12-13) age level. It was hypothesized that the introduction of body-checking at younger ages would result in higher overall rates of injury to minor hockey players, with concomitant increases in neurotraumatic injuries. PATIENTS AND METHODS: Participants included injured minor hockey players between the ages of 7 and 14 years in the Kingston area of Ontario, Canada. The Kingston sites of the Canadian Hospitals Injury Reporting and Prevention Program were used to identify injuries that presented to the only 2 emergency departments in this community. In our analyses, we compared rates and patterns of injury that required hospital-based emergency medicine care before (1997-1998 to 2001-2002 seasons) and after (2002-2003 to 2006-2007 seasons) implementation of the body-checking rule change. RESULTS: Overall rates of injury to minor hockey players declined in the years after the rule change. Rates of injury attributable to body-checking, as well as the natures and anatomic sites of injury caused by body-checking, remained consistent in the 2 study periods. CONCLUSIONS: In this historical study, we did not observe an increase in the overall rates of injury and concomitant neurotraumatic events. Increased enforcement of playing rules as well as temporal declines in emergency department use may have contributed to these findings. PMID- 20308212 TI - Growth hormone: health considerations beyond height gain. AB - The therapeutic benefit of growth hormone (GH) therapy in improving height in short children is widely recognized; however, GH therapy is associated with other metabolic actions that may be of benefit in these children. Beneficial effects of GH on body composition have been documented in several different patient populations as well as improvements in lipid profile. Marked augmentation of bone mineral density also seems evident in many pediatric populations. Some of these benefits may require continued therapy past the acquisition of adult height. With long-term therapy of any kind, the adverse consequences of treatment should also be considered. Fortunately, long-term GH treatment seems to be safe and well tolerated. This review describes the long-term metabolic effects of GH treatment in the pediatric population and considers how these may benefit children who are treated with GH. PMID- 20308213 TI - Culturally-sensitive information-sharing in pediatric palliative care. AB - OBJECTIVES: This study aimed to learn about experiences of Mexican American and Chinese American families who require pediatric palliative care. This article describes parents' perceptions of information-sharing by health care providers during their child's hospitalizations and at their child's death. METHODS: The study used a retrospective design of grounded theory analysis. Participants included 36 parents (26 Mexican American and 10 Chinese American) from 28 families who experienced between 6 months and 5 years before study participation the death of a child who was aged or =3 to 24 months and were administered the RNDA by 8 different professionals (3 physicians, 4 therapists, and 1 special teacher). Validity was determined on 34 children aged <3 months in hospital and 81 children aged > or =3 to 24 months in urban (n = 47) and rural (n = 34) community-based populations by any 1 of the 8 professionals, with simultaneous administration of the adapted Bayley Scales of Infant Development II by a psychologist as the gold standard. RESULTS: Mean kappa coefficients of agreement among professionals in overall and individual domains in the 2 age groups ranged from good to excellent. For both younger and older children, there was good concurrent validity (ie, significantly lower mean Mental Development Index and Psychomotor Development Index scores) for children with > or =1 neurodevelopmental impairment and for children with impairments in most functional domains, compared with children with no impairments. Significantly more impairments were found in children from disadvantaged compared with socioeconomically more advantaged communities, indicating good discriminant validity. CONCLUSIONS: The RNDA can be used by professionals from a range of backgrounds with high reliability and validity for determining functional status of children who are younger than 2 years. The study findings have important practical implications for early identification and intervention to mitigate neurodevelopmental impairments in large populations that live in developing countries where professional expertise is sparse. PMID- 20308215 TI - Multicenter study of repeat epinephrine treatments for food-related anaphylaxis. AB - OBJECTIVE: We sought to establish the frequency of receiving >1 dose of epinephrine in children who present to the emergency department (ED) with food related anaphylaxis. PATIENTS AND METHODS: We performed a medical chart review at Boston hospitals of all children presenting to the ED for food-related acute allergic reactions between January 1, 2001, and December 31, 2006. We focused on causative foods, clinical presentations, and emergency treatments. RESULTS: Through random sampling and appropriate weighting, the 605 reviewed cases represented a study cohort of 1255 patients. These patients had a median age of 5.8 years (95% confidence interval [CI]: 5.3-6.3), and the cohort was 62% male. A variety of foods provoked the allergic reactions, including peanuts (23%), tree nuts (18%), and milk (15%). Approximately half (52% [95% CI: 48-57]) of the children met diagnostic criteria for food-related anaphylaxis. Among those with anaphylaxis, 31% received 1 dose and 3% received >1 dose of epinephrine before their arrival to the ED. In the ED, patients with anaphylaxis received antihistamines (59%), corticosteroids (57%), epinephrine (20%). Over the course of their reaction, 44% of patients with food-related anaphylaxis received epinephrine, and among this subset of patients, 12% (95% CI: 9-14) received >1 dose. Risk factors for repeat epinephrine use included older age and transfer from an outside hospital. Most patients (88%) were discharged from the hospital. On ED discharge, 43% were prescribed self-injectable epinephrine, and only 22% were referred to an allergist. CONCLUSIONS: Among children with food-related anaphylaxis who received epinephrine, 12% received a second dose. Results of this study support the recommendation that children at risk for food-related anaphylaxis carry 2 doses of epinephrine. PMID- 20308216 TI - Placental inflammatory response is associated with poor neonatal growth: preterm birth cohort study. AB - OBJECTIVE: We sought to determine whether placental markers of intrauterine inflammation were associated with poor weight gain among premature infants in the neonatal period. METHODS: We reviewed 697 preterm births prospectively enrolled as part of an ongoing molecular epidemiological study. Placental markers and serial weight gain were analyzed for premature infants who were hospitalized for >/=21 days (N = 256). Placentas were examined for maternal inflammatory response (MIR), defined as subchorionitis, chorioamnionitis, deciduitis, or free membranitis, and fetal inflammatory response (FIR), defined as inflammation extending to the umbilical cord or chorionic plate. Multivariate linear regression and stratified analyses were performed. RESULTS: Decreases in weight gain at day 21 were associated with the presence of either MIR or FIR (beta coefficient = -4.63 +/- 1.41; P = .001). The association was stronger with FIR than MIR (P for trend = .0027) and persisted in the remaining hospitalized infants at day 28 (n = 223; beta coefficient = -5.53 +/- 1.85; P = .0028). Mean body weights were similar among the 3 groups by corrected age of 36 weeks or discharge, whichever came first. Associations between placental inflammation and poor growth persisted among infants with prenatal corticosteroid exposure and/or neonatal complications and remained marginally significant in the nonexposed groups. Among infants without intrauterine growth restriction, significant association persisted (n = 186; beta coefficient = -5.68 +/- 1.56; P = .0003). CONCLUSIONS: Placental inflammation is associated with poor neonatal growth. MIR and FIR may be useful markers for identifying infants at risk for postnatal growth failure. PMID- 20308217 TI - It's all about dwell time--reduce it and infection rates decrease? PMID- 20308218 TI - Innovation in pediatric education: the path to transforming pediatric graduate medical education. PMID- 20308219 TI - Widespread vitamin D deficiency in urban Massachusetts newborns and their mothers. AB - OBJECTIVE: To determine vitamin D status and associated factors in a cohort of newly delivered infants and their mothers in Boston, Massachusetts. PATIENTS AND METHODS: Enrollment in this cross-sectional study took place from 2005 to 2007 in an urban Boston teaching hospital with 2500 births per year. A questionnaire and medical-record data were used to identify variables that are potentially associated with vitamin D deficiency (25-hydroxyvitamin D [25(OH)D] < 20 ng/mL). Infant and maternal blood was obtained by venipuncture within 72 hours of birth. The main outcome measure was infant and maternal 25(OH)D status, assessed by competitive protein binding. RESULTS: We enrolled 459 healthy mother/infant pairs. After subsequent exclusions, analyses were performed on 376 newborns and 433 women. The median infant 25(OH)D level was 17.2 ng/mL (95% confidence interval [CI]: 16.0-18.8; range: <5.0 to 60.8 ng/mL). The median maternal 25(OH)D level was 24.8 ng/mL (95% CI: 23.2-25.8; range: <5.0 to 79.2 ng/mL). Overall, 58.0% of the infants and 35.8% of the mothers were vitamin D deficient (25[OH]D < 20 ng/mL); 38.0% of the infants and 23.1% of the mothers were severely deficient (25[OH]D < 15 ng/mL). Risk factors for infant vitamin D deficiency included maternal deficiency (adjusted odds ratio [aOR]: 5.28 [95% CI: 2.90-9.62]), winter birth (aOR: 3.86 [95% CI: 1.74-8.55]), black race (aOR: 3.36 [95% CI: 1.37 8.25]), and a maternal BMI of >/=35 (aOR: 2.78 [95% CI: 1.18-6.55]). Maternal prenatal-vitamin use throughout the second and third trimesters was protective against infant deficiency (aOR: 0.30 [95% CI: 0.16-0.56]). Similarly, prenatal vitamin use of > or =5 times per week in the third trimester was protective for mothers (aOR: 0.37 [95% CI: 0.20-0.69]). Despite this, >30% of the women who took prenatal vitamins were still vitamin D deficient at the time of birth. CONCLUSIONS: A high proportion of infants and their mothers in New England were vitamin D deficient. Prenatal vitamins may not contain enough vitamin D to ensure replete status at the time of birth. PMID- 20308220 TI - Current pediatrician practices in identifying high-risk behaviors of adolescents. AB - OBJECTIVE: In the United States, 15- to 24-year-olds represent approximately 14% of HIV cases diagnosed in 2006 and almost 50% of the 19 million sexually transmitted infections (STIs) reported annually. This survey assessed pediatricians' practices regarding preventive health care screening, provision of reproductive health services including HIV and STI screening and counseling, and barriers to providing these services. METHODS: A random-sample mailed survey of 1626 US members of the American Academy of Pediatrics in 2005.A total of 752 completed questionnaires were returned (46% response rate). Analysis was limited to the 468 pediatricians who provided health supervision visits to patients who were older than 11 years. RESULTS: Most pediatricians discussed sexual activity at preventive care visits; similar numbers discuss abstinence (62%), condoms (61%), and STIs (61%) with slightly fewer discussing HIV (54%). Pediatricians occasionally or rarely/never discussed homosexuality/sexual identity (82%). Most (71%) identified adolescents with high-risk behaviors by clinical interviews. Approximately 30% prescribed condoms, 22% distributed condoms, and 19% provided condom demonstrations. Whereas 46% of pediatricians recommended STI tests for all sexually active teens, only 28% recommended HIV testing for this population. Hospital/clinic-based and inner-city practitioners were more likely to prescribe, provide, and demonstrate condoms and recommend HIV/STI tests for sexually active teens. The most frequently identified barrier to HIV and STI prevention counseling was lack of time. CONCLUSIONS: Pediatricians believed it is important to deliver reproductive health services, and most addressed adolescent sexual activity at preventive care visits but did not routinely address homosexuality/sexual identity. Counseling and testing practices varied by physician characteristics. PMID- 20308221 TI - Adherence to vitamin D recommendations among US infants. AB - OBJECTIVES: In November 2008, the American Academy of Pediatrics (AAP) doubled the recommended daily intake of vitamin D for infants and children, from 200 IU/day (2003 recommendation) to 400 IU/day. We aimed to assess the prevalence of infants meeting the AAP recommended intake of vitamin D during their first year of life. METHODS: Using data from the Infant Feeding Practices Study II, conducted from 2005 to 2007, we estimated the percentage of infants who met vitamin D recommendations at ages 1, 2, 3, 4, 5, 6, 7.5, 9, and 10.5 months (n = 1952-1633). RESULTS: The use of oral vitamin D supplements was low, regardless of whether infants were consuming breast milk or formula, ranging from 1% to 13%, varying by age. Among infants who consumed breast milk but no formula, only 5% to 13% met either recommendation. Among mixed-fed infants, 28% to 35% met the 2003 recommendation, but only 9% to 14% would have met the 2008 recommendation. Among those who consumed formula but no breast milk, 81% to 98% met the 2003 recommendation, but only 20% to 37% would have met the 2008 recommendation. CONCLUSIONS: Our findings suggest that most US infants are not consuming adequate amounts of vitamin D according to the 2008 AAP recommendation. Pediatricians and health care providers should encourage parents of infants who are either breastfed or consuming <1 L/day of infant formula to give their infants an oral vitamin D supplement. PMID- 20308222 TI - Sensitivity of the pediatric early warning score to identify patient deterioration. AB - OBJECTIVE: We evaluated the Pediatric Early Warning Score (PEWS) sensitivity as an early indicator of patients deterioration leading to a Rapid Response Team (RRT)/code event. We hypothesized that at least 80% of patients had a critical PEWS preceding the event. We determined staff awareness of deterioration in patient status prior to the event as evidenced by consults, addition of monitoring equipment or increased frequency of assessment. The timing of these events was compared to critical PEWS times. METHODS: One hundred and seventy non ICU RRT and 16 code events were identified between October 2006 and February 2008. We completed retrospective PEWS at four-hour intervals or less for twenty four hours preceding the event. The PEWS algorithm, guiding staff to consult at a critical score > or =4 or a single domain score equal to 3, was applied. RESULTS: For 85.5% of patients the earliest indicator of deterioration, evidenced by a critical PEWS, was a median of 11 hours 36 minutes and the earliest preceding the event was 30 minutes. For 97.1% of patients the earliest median time to a consult was 80 minutes. Oximetry was added 6.9 hours for 43.5% of patients. 7% of patients had increased nursing assessment. A sub-group of patients had 1) critical PEWS, 2) consult and 3) addition of a monitor. The median time for earliest critical PEWS for these was significant (P < 0.001). CONCLUSION: PEWS can potentially provide a forewarning time >11 hours, alerting the team to adapt the care plan and possibly averting an RRT or code. PMID- 20308223 TI - Sociodemographic risk indicators of hookah smoking among White Americans: a pilot study. AB - BACKGROUND: Despite the sustained public health efforts to decrease cigarette smoking, there is an increasing trend in the use of alternative tobacco products that are perceived by some as less harmful. One example is hookah smoking. This study aimed to assess hookah trends among White Americans. METHODS: Two hundred and forty-five White American adults residing in southeast Michigan answered a self-administered standardized questionnaire that included basic demographics, socioeconomic status, and questions related to hookah smoking behavior. Logistic regression was used to determine risk indicators for hookah smoking. RESULTS: The combined prevalence of hookah smoking in the White American study population was 19%, with 10% of the sample smoking hookah only and 9% smoking both hookah and cigarettes. Approximately 19% of respondents believed that smoking hookah was less harmful than smoking cigarettes. Significant risk indicators for smoking hookah were being younger than 22 years and living with a family member who used tobacco. DISCUSSION: In addition to reporting the prevalence of use in this important group of potential users, we outline important sociodemographic risk factors for hookah use in a non-Arab American population. More research is needed with a larger population to better understand this new tobacco trend in order to curb a new potential health threat. PMID- 20308224 TI - Metabolic activation of heterocyclic amines and expression of CYP1A1 in the tongue. AB - Xenobiotic metabolism in oral tissues, especially in the tongue, has never been reported. In the present study, the metabolic activation/detoxification ability of promutagens in the tongue and the expression levels of related enzymes were investigated. Quantitative PCR analysis of rat tongue demonstrated constitutive messenger RNA (mRNA) expression of numerous drug-metabolizing enzymes. In particular, we detected mRNA, protein expression, and enzymatic activity of cytochrome P450 (CYP)1A1 in the tongue tissue. Metabolic activation of promutagens in the tongue was estimated using benzo[a]pyrene or heterocyclic amines (HCAs), found in cooked meat and tobacco products. Metabolic activation levels of HCAs in the tongue were comparable to those in the liver. In contrast, the expression levels of glutathione-S-transferase (GST) and uridine diphosphate glucuronosyltransferase (UGT) in the tongue were considerably lower compared with those in the liver, and as a result, the mutagenic activity in the tongue was not decreased by GST- or UGT-dependent conjugation. Treatment of rats with sudan III, a typical inducer of CYP1A1, resulted in markedly increased CYP1A1 mRNA, protein expressions, and CYP1A-dependent enzymatic and mutagenic activities. In addition, CYP1A1 mRNA expression in carcinoma cells (SAS) was induced by sudan III exposure. In conclusion, mutagenic activation of xenobiotics and an increased risk of cancer in the tongue were observed in this study. Furthermore, ingestion of drug-metabolizing enzyme inducers has the potential to increase the metabolic activation in the tongue tissue and increase the risk of biomolecular attack by promutagens. PMID- 20308226 TI - Cost-effectiveness of a programme to detect and provide better care for female victims of intimate partner violence. AB - OBJECTIVE: Primary care clinicians often fail to detect women who are victims of intimate partner violence (IPV). Our aim was to investigate the cost effectiveness of a programme in primary care to detect and support such women. METHODS: We developed a Markov model to estimate the cost-effectiveness of education and support for primary care clinicians to increase their identification of survivors of IPV and to refer them to a specialist advocacy agency or a psychologist with specialist skills. The programme was implemented in three general practices in the United Kingdom (with an additional practice acting as a control) and provided cost data and rates of identification and referral. Other cost data and the effectiveness of IPV advocacy came from published sources. RESULTS: The model gave an incremental cost-effectiveness ratio (ICER) of approximately pounds sterling 2,450 per quality adjusted life year (QALY). Although the ratio increased in some of the sensitivity analyses, most were under a conventional willingness to pay threshold (pounds sterling 30,000/QALY). CONCLUSIONS: While there is considerable uncertainty in the underlying parameters, a training programme for primary care teams to increase identification and referral of women experiencing IPV is likely to be cost effective. PMID- 20308227 TI - Hyperthyroidism and venous thrombosis: a casual or causal association? A systematic literature review. AB - A kaleidoscope of coagulation disorders have been reported in patients with thyroid dysfunctions. Globally, these disorders involve both primary and secondary hemostasis and range from subclinical laboratory abnormalities to, more rarely, life-threatening hemorrhages or thrombotic events. While overt hypothyroidism appears to be associated with a bleeding tendency, hyperthyroidism emerged to have an increased risk of thrombotic events. In particular, a number of case reports have documented acute venous thrombosis complications in patients with overt hyperthyroidism, especially at cerebral sites. Nevertheless, further observational and intervention studies might be needed to provide a more definitive information on the clinical relevance of this association, along with the potential implication for prevention and treatment of coagulation fibrinolytic abnormalities in patients with thyroid dysfunction. PMID- 20308225 TI - Arsenic exposure perturbs epithelial-mesenchymal cell transition and gene expression in a collagen gel assay. AB - Arsenic is a naturally occurring metalloid and environmental contaminant. Arsenic exposure in drinking water is reported to cause cancer of the liver, kidneys, lung, bladder, and skin as well as birth defects, including neural tube, facial, and vasculogenic defects. The early embryonic period most sensitive to arsenic includes a variety of cellular processes. One key cellular process is epithelial mesenchymal transition (EMT) where epithelial sheets develop into three dimensional structures. An embryonic prototype of EMT is found in the atrioventricular (AV) canal of the developing heart, where endothelia differentiate to form heart valves. Effects of arsenic on this cellular process were examined by collagen gel invasion assay (EMT assay) using explanted AV canals from chicken embryo hearts. AV canals treated with 12.5-500 ppb arsenic showed a loss of mesenchyme at 12.5 ppb, and mesenchyme formation was completely inhibited at 500 ppb. Altered gene expression in arsenic-treated explants was investigated by microarray analysis. Genes whose expression was altered consistently at exposure levels of 10, 25, and 100 ppb were identified, and results showed that 25 ppb in vitro was particularly effective. Three hundred and eighty two genes were significantly altered at this exposure level. Cytoscape analysis of the microarray data using the chicken interactome identified four clusters of altered genes based on published relationships and pathways. This analysis identified cytoskeleton and cell adhesion-related genes whose disruption is consistent with an altered ability to undergo EMT. These studies show that EMT is sensitive to arsenic and that an interactome-based approach can be useful in identifying targets. PMID- 20308228 TI - Asymptomatic saddle pulmonary embolism: case report and literature review. AB - Saddle pulmonary embolism is defined as a visible thromboembolus straddling the bifurcation of the main pulmonary artery trunk. Patient with saddle pulmonary embolism have a 2-week mortality of 5.8%. 46 years old, hypertensive male, presented with right leg swelling and pain, with no evidence of cardiopulmonary distress. CTA showed a large saddle pulmonary embolus. Doppler ultrasound of right lower extremity, revealed a large filling defect extending from the common femoral vein distally involving the deep femoral vein, femoral vein and popliteal vein on the right. Diagnosis of saddle embolus on its own is not associated with an unfavorable outcome, therefore should not influence management of PE. Echocardiography done within 48 hours in-patient with symptomatic saddle pulmonary embolism reveals mild to moderate right ventricular enlargement in 90% and mild to severe right ventricular dysfunction in 80%. Emerging evidence suggest that primary therapy with thrombolytics and embolectomy, should be used in PE patients who presents with hypotension plus moderate to severe right ventricular dysfunction on echo cardiogram. Patients with saddle pulmonary embolism can have normal cardiopulmonary reserve; these patients can be managed with conventional treatment for pulmonary embolism in hospital settings, in order to deal with any complications developed during management. Aggressive management should be reserved for patients who are hemodynamically unstable as well as those with echocardiographic evidence of severe right ventricular strain. Physicians should decrease their threshold for suspicion of pulmonary embolism in patients with deep venous thrombosis in the hope of revealing more and more hidden cases of pulmonary embolism. PMID- 20308229 TI - Prothrombin complex concentrate such as therapy and prophylaxis in factor X deficient patient (Friuli variant). AB - BACKGROUND: Factor X (FX) deficiency is a serious, rare bleeding disorder, with 1 in 500 000 affected people. Hemorrhages, hematuria, epistaxis, and other bleeding complications are frequent. CASE REPORT: Now, we report a case of a well-known 77 year-old FX-deficient patient (Friuli variant, level <1%, mutation Pro(343)->Ser, exon VIII) with hypertension, chronic obstructive pulmonary disease (COPD), and chronic gastritis, admitted many times to hospital due to surgical complications after aortic abdominal aneurysm (AAA) repair. Use of prothrombin complex concentrate (PCC) such as hemostatic therapy during surgeries and prophylaxis after discharge is shown in this article. Three consecutive surgeries were considered. First, endoleak postendoprosthesis; second, AAA breakage; and third, planned surgery, a new endovascular prosthesis positioning and femur-femoral bypass. No adverse events due to PCC were found by local physicians. DISCUSSION: We discuss the methods commonly used in the treatment and prophylaxis of patients with FX deficiency to reduce hemorrhagic risk and to improve their quality of life. CONCLUSION: Waiting for specific therapeutic options for FX deficiency, currently, the best treatment is represented by PCC. Its correct use permits an improvement in life quality and a reduction in bleeding frequency in FX-deficient patients. PMID- 20308230 TI - Relationship between psychological distress and endogenous anticoagulants in patients with a previous venous thromboembolic event. AB - BACKGROUND: Psychological distress, particularly anxiety and depression, has been associated with a prothrombotic state. However, the relationship between psychosocial factors and endogenous anticoagulants protein S (PS) and protein C (PC) has not previously been investigated. We explored the association between psychological distress, PS, and PC in patients with an objectively diagnosed venous thromboembolic event (VTE). METHODS: We investigated 126 consecutively enrolled patients >=3 months after VTE (ie, deep venous thrombosis and/or pulmonary embolism) and >=1 month of discontinuation of oral anticoagulants. Approximately 10 days before blood collection for thrombophilia workup, anxiety and depression scores were assessed using the Hospital Anxiety and Depression scale (HADS). Protein C and S were determined by routine laboratory assays. RESULTS: After controlling for demographic and medical factors, PC, as measured by the PC-activated partial thromboplastin time (aPTT) method and the PC chromatin substrate method, was positively associated with psychological distress (sum of anxiety plus depression symptoms; P <= .027), anxiety (P <= .055), and depression (P <= .031), explaining between 3% and 6% of the variance. Total PS antigen showed a direct relationship with psychological distress (P = .025) and depression (P = .005), explaining 5% and 7% of respective variances. Free PS showed a positive association with depression (P = .046), explaining 3% of the variance. Anxiety showed no independent association with either PS measure. CONCLUSIONS: Psychological distress is independently associated with enhanced endogenous anticoagulant potential. This might reflect a counterregulatory mechanism to outweigh the previously observed hypercoagulability in individuals under chronic stress and with elevated symptoms of anxiety and depression. PMID- 20308231 TI - Molecular characterization of FXI deficiency. AB - Factor XI (FXI) deficiency is a rare autosomal bleeding disease associated with genetic defects in the FXI gene. It is a heterogeneous disorder with variable tendency in bleeding and variable causative FXI gene mutations. It is characterized as a cross-reacting material-negative (CRM-) FXI deficiency due to decreased FXI levels or cross-reacting material-positive (CRM+) FXI deficiency due to impaired FXI function. Increasing number of mutations has been reported in FXI mutation database, and most of the mutations are affecting serine protease (SP) domain of the protein. Functional characterization for the mutations helps to better understand the molecular basis of FXI deficiency. Prevalence of the disease is higher in certain populations such as Ashkenazi Jews. The purpose of this review is to give an overview of the molecular basis of congenital FXI deficiency. PMID- 20308233 TI - Clinical research in the UK: back from the brink, but are neurologists missing the boat? PMID- 20308234 TI - Managing acute behavioural disturbance in a neurology ward. AB - Episodes of behavioural disturbance are commonplace on neurology wards. The key to their safe management is prior planning, including securing the safety of the ward environment, and a formal risk assessment. Protocols which define staff roles and the unit strategy for the management of behavioural disturbance should be formally agreed and appropriate training provided. The commonest cause of disturbed behaviour in neurology-and neurosurgical wards-is delirium. This presents with fluctuating orientation, grossly impaired attention and disruption of the sleep-wake cycle. The cause is generally multifactorial with a combination of pre-existing vulnerabilities and acute precipitants. Management reflects this and depends on a multifaceted approach to medical care, including basic supportive measures, minimising polypharmacy and promoting orientation, early mobilisation and nutritional status, as well as treating the underlying medical conditions. Antipsychotic medication has a specific treatment effect but never as the only approach to the management of the delirious patient. PMID- 20308235 TI - The neurofibromatoses. AB - Neurofibromatosis 1 (NF1) and neurofibromatosis 2 (NF2) are inherited autosomal dominant disorders that have a significant impact on the nervous system and predispose to tumour formation. The current nomenclature makes NF1 and NF2 awkward bedfellows because they are clinically and genetically separate disorders. Neurofibromas are characteristic of NF1, a common condition with major skin involvement and many clinical complications. By contrast, schwannomas are the distinctive lesions in NF2, cutaneous signs are less prominent in this rarer disorder and clinical manifestations are largely restricted to the nervous system and eye. The current aim of neurofibromatosis specialists is to provide cohesive standards of care for everyone with neurofibromatosis and to devise standardised protocols for assessment and management within a multidisciplinary setting. PMID- 20308236 TI - Brain microbleeds. AB - Brain microbleeds are small dot-like lesions appearing as hyposignal on gradient echo T2* MR sequences. They represent microscopic areas of old haemosiderin deposits. They are frequent in the setting of symptomatic cerebrovascular disease and also in older healthy people, suggesting a link with cerebral amyloid angiopathy. Their use as diagnostic or prognostic biomarkers remains uncertain. More recently, they have been highlighted as a potential key factor in the pathogenesis of Alzheimer's disease, connecting the main pathological contributors of amyloid accumulation and cerebrovascular damage. The increasing use of MRI in clinical practice and research has brought brain microbleeds very much to our attention, raising many clinical dilemmas, such as-what do they mean? Should I treat a patient with antithrombotic drugs or thrombolysis? And many others. PMID- 20308237 TI - The imploding antrum syndrome: an unusual cause of double vision. AB - A 42-year-old man presented with a 3 day history of drooping of the right eyelid and intermittent double vision. He was found to have mechanical restriction of the left eye in elevation and MRI demonstrated an abnormality in the left maxillary sinus with descent of the left inferior rectus muscle. CT confirmed the diagnosis of 'imploding antrum' or 'silent sinus' syndrome. It was treated surgically with complete resolution of symptoms and signs. PMID- 20308238 TI - CMT, a life sentence not a death sentence. PMID- 20308239 TI - What got me into neurology (and did it work out?). PMID- 20308240 TI - The groom who could not say "I do". PMID- 20308241 TI - Jordan. PMID- 20308242 TI - The bare essentials: hyperkinetic movement disorders: shakes, jumps and jolts. PMID- 20308243 TI - A mixed-methods prospective study of death certification in general practice. AB - BACKGROUND: Accurate completion of death certificates is important for compiling national and regional statistics. Determining actual cause of death can be extremely difficult; internationally, uncertainty has been acknowledged in many cases. We set out to explore the issue of uncertainty further: in what circumstances do GPs feel more or less certain, and how do they feel about this? OBJECTIVES: The study aimed (i) to focus on death certification issues faced by GPs and their related attitudes, and (ii) to assess GPs' confidence in stated diagnosis and reasons influencing certification. METHODS: This was a prospective, cross-sectional, mixed-methods study. Participants were 15 GP trainers in Ireland. Two focus groups, held 1 year apart, explored issues surrounding, and attitudes towards, death certification. A one-page questionnaire, completed after the death of every patient for 6 months, recorded patient age and gender, place and certified cause of death, certifier, and level of certainty about cause of death (on a 10-point scale). RESULTS: There were 168 deaths across the 15 practices during the study period. Overall confidence in certified cause of death was relatively high but varied significantly according to certifier, and place and cause of death. The main issues surrounded the varying level of certainty with diagnosis, concerns regarding the family of the deceased, and the perceived gap in education about death certification, including legal matters. CONCLUSIONS: GPs appear to feel in an ambivalent or invidious position where death certification is required, a situation that could be addressed in postgraduate training settings. PMID- 20308244 TI - Post-infectious gastrointestinal symptoms after acute Giardiasis. A 1-year follow up in general practice. AB - BACKGROUND: Giardia lamblia is endemic in many tropical and subtropical areas of the world, and in Europe and North America a common cause of waterborne outbreaks of gastroenteritis. In 2004, approximately 5000 people were sick with giardiasis during an outbreak in Bergen, Norway. OBJECTIVE: To investigate the presence of gastrointestinal complaints and persistent infection in a 1-year period after acute giardiasis. METHODS: From a population (N = 7100) assigned to two general practice clinics, a cohort of 134 patients with clinically defined giardiasis was identified. Of these, 118 gave consent to take part in this study. The patients were asked to submit stool samples 6 months after the acute infection and to return questionnaires delivered by mail 6 and 12 months after the outbreak. Main outcome measures were proportion of patients with persistent infection and/or gastrointestinal symptoms. RESULTS: Stool samples were submitted by 69.5% (82/118) of the patients after 6 months, and three were positive for G. lamblia. After 6 months, 37.3% (44/118) of the patients reported gastrointestinal symptoms related to their Giardia infection. This proportion went down to 19.2% (19/99) after 12 months. The reported water intake prior to the outbreak was significantly higher in patients with persistent symptoms, but there was no association with gender and neuroticism as has been shown in other studies of functional gastrointestinal disorders. CONCLUSION: Persistent gastrointestinal symptoms are a common complication after giardiasis in a population most likely previously unexposed to G. lamblia. The results show the need for further investigation of the mechanism involved. PMID- 20308245 TI - Differences in the primary care management of patients with psychosis from two ethnic groups: a population-based cross-sectional study. AB - BACKGROUND: Ethnicity is an important dimension in many aspects of psychosis. OBJECTIVE: To investigate ethnic differences in the primary care management of patients with psychosis. METHODS: Data were obtained from Lambeth DataNet, a database of computerized general practice case records derived from practices in an inner city London borough. We undertook a cross-sectional survey of patients with psychosis. OUTCOME MEASURES: health screening, chronic disease management and prescribing data and differences between ethnic groups were expressed as odds ratios (ORs). RESULTS: One thousand six hundred and ninety-four of 165,911 (1.02%) registered patients had a diagnosis of psychosis; 1090 (64%) had ethnicity recorded; 501 were White and 403 were Black or Black British. There were no significant ethnic differences for blood pressure, cholesterol or HbA1c monitoring or control; cervical or mammography screening; treatment with hypotensives, statins, antidepressants, lithium, antipsychotics or atypical antipsychotics. Depot injectable antipsychotics were more likely to be prescribed to Black patients than other delivery modes: OR 2.10 (95% CI: 1.20-3.67). CONCLUSIONS: Measurable aspects of physical health care of patients with psychosis were similar, regardless of ethnicity. Increased use of the depot antipsychotic medication in black patients needs further exploration. PMID- 20308246 TI - Overcoming the barriers to chlamydia screening in general practice--a qualitative study. AB - BACKGROUND: There is low uptake of chlamydia screening in general practices registered with the English National Chlamydia Screening Programme (NCSP). Aims. To explore staff's attitudes and behaviour around chlamydia screening and how screening could be optimized in general practice. METHODS: A qualitative study with focus groups and interviews, in general practices in seven NCSP areas. Twenty-five focus groups and 12 interviews undertaken with a purposively selected diverse group of high and low chlamydia-screening practices in 2006-08. Data were collected and analysed using a framework analytical approach. RESULTS: Higher screening practices had more staff with greater belief in patient and population benefits of screening and, as screening was a subjective norm, it was part of every day practice. Many staff in the majority of other practices were uncomfortable raising chlamydia opportunistically and time pressures meant that any extra public health issues covered within a consultation were determined by Quality Outcomes Framework (QOF) targets. All practices would value more training and feedback about their screening rates and results. Practices suggested that use of computer prompts, simplified request forms and more accessible kits could increase screening. CONCLUSION: Practice staff need more evidence of the value of opportunistic chlamydia screening in men and women; staff development to reduce the barriers to broaching sexual health; simpler request forms and easily accessible kits to increase their ability to offer it within the time pressures of general practice. Increased awareness of chlamydia could be attained through practice meetings, computer templates and reminders, targets and incentives or QOF points with feedback. PMID- 20308247 TI - Rem, a member of the RGK GTPases, inhibits recombinant CaV1.2 channels using multiple mechanisms that require distinct conformations of the GTPase. AB - Rad/Rem/Gem/Kir (RGK) GTPases potently inhibit Ca(V)1 and Ca(V)2 (Ca(V)1-2) channels, a paradigm of ion channel regulation by monomeric G-proteins with significant physiological ramifications and potential biotechnology applications. The mechanism(s) underlying how RGK proteins inhibit I(Ca) is unknown, and it is unclear how key structural and regulatory properties of these GTPases (such as the role of GTP binding to the nucleotide binding domain (NBD), and the C terminus which contains a membrane-targeting motif) feature in this effect. Here, we show that Rem inhibits Ca(V)1.2 channels by three independent mechanisms that rely on distinct configurations of the GTPase: (1) a reduction in surface density of channels is accomplished by enhancing dynamin-dependent endocytosis, (2) a diminution of channel open probability (P(o)) that occurs without impacting on voltage sensor movement, and (3) an immobilization of Ca(V) channel voltage sensors. The presence of both the Rem NBD and C-terminus (whether membrane targeted or not) in one molecule is sufficient to reconstitute all three mechanisms. However, membrane localization of the NBD by a generic membrane targeting module reconstitutes only the decreased P(o) function (mechanism 2). A point mutation that prevents GTP binding to the NBD selectively eliminates the capacity to immobilize voltage sensors (mechanism 3). The results reveal an uncommon multiplicity in the mechanisms Rem uses to inhibit I(Ca), predict new physiological dimensions of the RGK GTPase-Ca(V) channel crosstalk, and suggest original approaches for developing novel Ca(V) channel blockers. PMID- 20308248 TI - Exercise intensity-dependent regulation of peroxisome proliferator-activated receptor coactivator-1 mRNA abundance is associated with differential activation of upstream signalling kinases in human skeletal muscle. AB - Skeletal muscle contraction increases intracellular ATP turnover, calcium flux, and mechanical stress, initiating signal transduction pathways that modulate peroxisome proliferator-activated receptor gamma coactivator-1alpha (PGC-1alpha) dependent transcriptional programmes. The purpose of this study was to determine if the intensity of exercise regulates PGC-1alpha expression in human skeletal muscle, coincident with activation of signalling cascades known to regulate PGC 1alpha transcription. Eight sedentary males expended 400 kcal (1674 kj) during a single bout of cycle ergometer exercise on two separate occasions at either 40% (LO) or 80% (HI) of . Skeletal muscle biopsies from the m. vastus lateralis were taken at rest and at +0, +3 and +19 h after exercise. Energy expenditure during exercise was similar between trials, but the high intensity bout was shorter in duration (LO, 69.9 +/- 4.0 min; HI, 36.0 +/- 2.2 min, P < 0.05) and had a higher rate of glycogen utilization (P < 0.05). PGC-1alpha mRNA abundance increased in an intensity-dependent manner +3 h after exercise (LO, 3.8-fold; HI, 10.2-fold, P < 0.05). AMP-activated protein kinase (AMPK) (2.8-fold, P < 0.05) and calcium/calmodulin-dependent protein kinase II (CaMKII) phosphorylation (84%, P < 0.05) increased immediately after HI but not LO. p38 mitogen-activated protein kinase (MAPK) phosphorylation increased after both trials (2.0-fold, P < 0.05), but phosphorylation of the downstream transcription factor, activating transcription factor-2 (ATF-2), increased only after HI (2.4-fold, P < 0.05). Cyclic-AMP response element binding protein (CREB) phosphorylation was elevated at +3 h after both trials (80%, P < 0.05) and class IIa histone deacetylase (HDAC) phosphorylation increased only after HI (2.0-fold, P < 0.05). In conclusion, exercise intensity regulates PGC-1alpha mRNA abundance in human skeletal muscle in response to a single bout of exercise. This effect is mediated by differential activation of multiple signalling pathways, with ATF-2 and HDAC phosphorylation proposed as key intensity-dependent mediators. PMID- 20308249 TI - Kv1.3 is the exclusive voltage-gated K+ channel of platelets and megakaryocytes: roles in membrane potential, Ca2+ signalling and platelet count. AB - A delayed rectifier voltage-gated K(+) channel (Kv) represents the largest ionic conductance of platelets and megakaryocytes, but is undefined at the molecular level. Quantitative RT-PCR of all known Kv alpha and ancillary subunits showed that only Kv1.3 (KCNA3) is substantially expressed in human platelets. Furthermore, megakaryocytes from Kv1.3(/) mice or from wild-type mice exposed to the Kv1.3 blocker margatoxin completely lacked Kv currents and displayed substantially depolarised resting membrane potentials. In human platelets, margatoxin reduced the P2X(1)- and thromboxaneA(2) receptor-evoked [Ca(2+)](i) increases and delayed the onset of store-operated Ca(2+) influx. Megakaryocyte development was normal in Kv1.3(/) mice, but the platelet count was increased, consistent with a role of Kv1.3 in apoptosis or decreased platelet activation. We conclude that Kv1.3 forms the Kv channel of the platelet and megakaryocyte, which sets the resting membrane potential, regulates agonist-evoked Ca(2+) increases and influences circulating platelet numbers. PMID- 20308250 TI - N-Acetylcysteine infusion does not affect glucose disposal during prolonged moderate-intensity exercise in humans. AB - There is evidence that reactive oxygen species (ROS) signalling is required for normal increases in glucose uptake during contraction of isolated mouse skeletal muscle, and that AMP-activated protein kinase (AMPK) is involved. The aim of this study was to determine whether ROS signalling is involved in the regulation of glucose disposal and AMPK activation during moderate-intensity exercise in humans. Nine healthy males completed 80 min of cycle ergometry at 62 +/- 1% of peak oxygen consumption ( V(O(2)peak).A 6,6-(2)H-glucose tracer was infused at rest and during exercise, and in a double-blind randomised cross-over design, N acetylcysteine (NAC) or saline (CON) was co-infused. NAC was infused at 125 mg kg(1) h(1) for 15 min and then at 25 mg kg(1) h(1) for 20 min before and throughout exercise. NAC infusion elevated plasma NAC and cysteine, and muscle NAC and cysteine concentrations during exercise. Although neither NAC infusion nor exercise significantly affected muscle reduced or oxidised glutathione (GSH or GSSG) concentration (P > 0.05), S-glutathionylation (an indicator of oxidative stress) of a protein band of approximately 270 kDa was increased approximately 3 fold with contraction and this increase was prevented by NAC infusion. Despite this, exercised-induced increases in tracer determined glucose disposal, plasma lactate, plasma non-esterified fatty acids (NEFAs), and decreases in plasma insulin were not affected by NAC infusion. In addition, skeletal muscle AMPKalpha and acetyl-CoA carboxylase-beta (ACCbeta) phosphorylation increased during exercise by approximately 3- and approximately 6-fold (P < 0.05), respectively, and this was not affected by NAC infusion. Unlike findings in mouse muscle ex vivo, NAC does not attenuate skeletal muscle glucose disposal or AMPK activation during moderate-intensity exercise in humans. PMID- 20308251 TI - Mutations in GABAA receptor subunits associated with genetic epilepsies. AB - Mutations in inhibitory GABAA receptor subunit genes (GABRA1, GABRB3, GABRG2 and GABRD) have been associated with genetic epilepsy syndromes including childhood absence epilepsy (CAE), juvenile myoclonic epilepsy (JME), pure febrile seizures (FS), generalized epilepsy with febrile seizures plus (GEFS+), and Dravet syndrome (DS)/severe myoclonic epilepsy in infancy (SMEI). These mutations are found in both translated and untranslated gene regions and have been shown to affect the GABAA receptors by altering receptor function and/or by impairing receptor biogenesis by multiple mechanisms including reducing subunit mRNA transcription or stability, impairing subunit folding, stability, or oligomerization and by inhibiting receptor trafficking. PMID- 20308252 TI - Common phenotype of resting mouse extensor digitorum longus and soleus muscles: equal ATPase and glycolytic flux during transient anoxia. AB - Rates of ATPase and glycolysis are several times faster in actively contracting mouse extensor digitorum longus muscle (EDL) than soleus (SOL), but we find these rates are not distinguishable at rest. We used a transient anoxic perturbation of steady state energy balance to decrease phosphocreatine (PCr) reversibly and to measure the rates of ATPase and of lactate production without muscle activation or contraction. The rate of glycolytic ATP synthesis is less than the ATPase rate, accounting for the continual PCr decrease during anoxia in both muscles. We fitted a mathematical model validated with properties of enzymes and solutes measured in vitro and appropriate for the transient perturbation of these muscles to experimental data to test whether the model accounts for the results. Simulations showed equal rates of ATPase and lactate production in both muscles. ATPase controls glycolytic flux by feedback from its products. Adenylate kinase function is critical because a rise in [AMP] is necessary to activate glycogen phosphorylase. ATPase is the primary source of H+ production. The sum of contributions of the 13 reactions of the glycogenolytic and glycolytic network to total proton load is negligible. The stoichiometry of lactate and H+ production is near unity. These results identify a default state of energy metabolism for resting muscle in which there is no difference in the metabolic phenotype of EDL and SOL. Therefore, additional control mechanisms, involving higher ATPase flux and [Ca2+], must exist to explain the well-known difference in glycolytic rates in fast-twitch and slow-twitch muscles in actively contracting muscle. PMID- 20308253 TI - An in vivo tethered toxin approach for the cell-autonomous inactivation of voltage-gated sodium channel currents in nociceptors. AB - Understanding information flow in sensory pathways requires cell-selective approaches to manipulate the activity of defined neurones. Primary afferent nociceptors, which detect painful stimuli, are enriched in specific voltage-gated sodium channel (VGSC) subtypes. Toxins derived from venomous animals can be used to dissect the contributions of particular ion currents to cell physiology. Here we have used a transgenic approach to target a membrane-tethered isoform of the conotoxin MrVIa (t-MrVIa) only to nociceptive neurones in mice. T-MrVIa transgenic mice show a 44 +/- 7% reduction of tetrodotoxin-resistant (TTX-R) VGSC current densities. This inhibition is permanent, reversible and does not result in functional upregulation of TTX-sensitive (TTX-S) VGSCs, voltage-gated calcium channels (VGCCs) or transient receptor potential (TRP) channels present in nociceptive neurones. As a consequence of the reduction of TTX-R VGSC currents, t MrVIa transgenic mice display decreased inflammatory mechanical hypersensitivity, cold pain insensitivity and reduced firing of cutaneous C-fibres sensitive to noxious cold temperatures. These data validate the use of genetically encoded t toxins as a powerful tool to manipulate VGSCs in specific cell types within the mammalian nervous system. This novel genetic methodology can be used for circuit mapping and has the key advantage that it enables the dissection of the contribution of specific ionic currents to neuronal function and to behaviour. PMID- 20308254 TI - Ganglionic transmission in a vasomotor pathway studied in vivo. AB - Intracellular recordings were made in vivo from 40 spontaneously active cells in the third lumbar sympathetic ganglion of urethane-anaesthetized rats. In 38/40 cells ongoing action potentials showed strong cardiac rhythmicity (93.4 +/- 1.9% modulation) indicating high barosensitivity and probable muscle vasoconstrictor (MVC) function. Subthreshold excitatory postsynaptic potentials (EPSPs) showed the same pattern. The 38 barosensitive neurons fired action potentials at 2.9 +/- 0.3 Hz. All action potentials were triggered by EPSPs, most of which were unitary events. Calculations indicated that <5% of action potentials were triggered by summation of otherwise subthreshold EPSPs. 'Dominant' synaptic inputs with a high safety factor were identified, confirming previous work. These were active in 24/38 cells and accounted for 32% of all action potentials; other ('secondary') inputs drove the remainder. Inputs (21 dominant, 19 secondary) attributed to single preganglionic neurons fired at 1.38 +/- 0.16 Hz. An average of two to three preganglionic neurons were estimated to drive each ganglion cell's action potentials. When cells were held hyperpolarized to block spiking, a range of spontaneous EPSP amplitudes was revealed. Threshold equivalent was defined as the membrane potential value that was exceeded by spontaneous EPSPs at the same frequency as the cell's original firing rate. In 10/12 cells examined, a continuum of EPSP amplitudes overlapped threshold equivalent. Small changes in cell excitability could therefore raise or lower the percentage of preganglionic inputs triggering action potentials. The results indicate that vasoconstrictor ganglion cells in vivo mostly behave not as 1:1 relays, but as continuously variable gates. PMID- 20308255 TI - Cobalt asthma--a case series from a cobalt plant. AB - BACKGROUND: Cobalt has been shown to induce mainly asthma, allergic contact dermatitis and hard metal disease. The data on cobalt asthma are mainly based on case reports. AIMS: To characterize all the cases of occupational cobalt asthma encountered in a cobalt plant at the time of diagnosis and 6 months later. We also evaluated the incidence of cobalt asthma in different departments on the basis of data on occupational exposures. METHODS: We identified cases of cobalt asthma confirmed with specific bronchial challenge tests in the Kokkola cobalt plant in Finland where exposure levels have been regularly monitored. RESULTS: Between 1967 and 2003, a total of 22 cases of cobalt asthma were diagnosed in the cobalt plant. On challenge tests, mostly late or dual asthmatic reactions were observed. The incidence of cobalt asthma was the highest in the departments with the highest cobalt exposure levels. All cases of cobalt asthma were encountered in departments where irritant gases were present in the ambient air in addition to cobalt. At the time of the follow-up examination 6 months later, non-specific hyperreactivity had mostly remained at the same level or increased. CONCLUSIONS: The incidence of cobalt asthma correlated with the exposure levels of cobalt in corresponding departments. An irritating effect of gaseous compounds may enhance the risk of cobalt asthma and even the smallest amounts of cobalt may be harmful to susceptible workers. Symptoms of asthma may continue despite the fact that occupational exposure to cobalt has ceased. PMID- 20308256 TI - Correlates of short- and long-term absence due to musculoskeletal disorders. AB - BACKGROUND: Musculoskeletal disorders (MSD) are a common cause of disability and absence from work. There is no consistent evidence in the literature regarding predictors for short- and long-term absences due to these disorders. AIMS: To investigate work-related factors influencing short- and long-term absences due to MSD in German-speaking countries. METHODS: The study is based on data from the Fourth European Working Conditions Survey. The study population included 2849 workers in German-speaking countries who participated in face-to-face interviews. Logistic regression models were used to determine the associations between possible risk factors and the occurrence of short- or long-term absence due to MSD. RESULTS: A tiring or painful working position was positively correlated with short- and long-term absenteeism due to MSD, whereas the freedom to decide when to take holidays was negatively associated with this phenomenon. Some psychosocial factors, such as the ability to apply one's own ideas at work, the ability to choose or change the speed or rate of work and the emotional demands of the job, had contradictory impacts on short- and long-term absenteeism due to MSD. CONCLUSIONS: The results of this investigation show that it is important to distinguish between predictors of short- and long-term absenteeism due to MSD. PMID- 20308257 TI - The benefits of sustained leisure-time physical activity on job strain. AB - BACKGROUND: The long-term effects of leisure-time physical activity (LTPA) on job strain have not been assessed in a large prospective population-based cohort study. AIMS: To examine the relationship between the LTPA and the prevalence of job strain. METHODS: The participants were 861 full-time employees (406 men and 455 women), aged 24-39 years in 2001, from the ongoing Cardiovascular Risk in Young Finns Study. LTPA was assessed using a self-report questionnaire in 1992 and in 2001. The participants were grouped into four categories according to tertiles of LTPA index at two time points: persistently active, increasingly active, decreasingly active and persistently inactive. Job strain was measured in 2001 by indicators of job demands and job control. RESULTS: Baseline LTPA was inversely associated with job strain (P < 0.001) and job demands (P < 0.05) and directly associated with job control (P < 0.05) in both sexes in a model adjusted for the change in 9-year LTPA, age, educational level, occupational status and smoking. Compared with persistently active participants, persistently inactive participants had a 4.0-fold higher job strain after adjustment for the confounders. Similarly, persistently inactive participants had a 2.7-fold higher job demands and a 1.8-fold lower job control. Decreasing physical activity was independently associated with high job strain (P < 0.01) and with low job control (P < 0.01). CONCLUSIONS: Participation in regular LTPA during leisure may help young adults to cope with job strain. A long-term benefit of LTPA may play a role in the development of mental well-being. PMID- 20308258 TI - Job strain among Malaysian office workers of a multinational company. AB - BACKGROUND: Information on job strain exposure among Malaysian workers in multinational companies is limited. AIMS: To investigate the prevalence and factors associated with high job strain among office workers of a multinational company in Malaysia. METHODS: A cross-sectional study was conducted in November 2007 among 470 eligible workers. Respondents self-administered the Job Content Questionnaire downloaded from the company's intranet. A median-split procedure was applied to create four groups according to the Job Demand-Control Model: active, passive, high and low job strain. Logistic regression models were used to investigate the associations between socio-demographic, occupational and psychosocial factors and high job strain. RESULTS: A total of 356 questionnaires were received (response rate 76%). Twenty-one per cent of respondents were in the high job strain group, 35% were in the passive group, whereas 26% and 17% of workers were in the low strain and active groups, respectively. After controlling for confounders, three factors were found to be associated with high job strain: male workers (adjusted OR 1.94, 95% CI 1.04-3.64), working >48 h per week (adjusted OR 2.51, 95% CI 1.44-4.39) and job insecurity (adjusted OR 1.14, 95% CI 1.02-1.27). One protective factor for high job strain was the scale 'created skill', which is part of skill discretion (adjusted OR 0.70, 95% CI 0.57-0.86). CONCLUSIONS: About one in five workers in this study experience high job strain. Work improvement measures include reducing long working hours and job insecurity and giving workers the opportunity to learn, use creativity and develop abilities. PMID- 20308259 TI - Laboratory work and adverse pregnancy outcomes. AB - BACKGROUND: Laboratory workers are commonly exposed to chemical, biological and physical agents. They also may adopt poor postures for long periods and be engaged in moving and handling. These factors may increase the risk of adverse pregnancy outcome in female laboratory workers. AIMS: To assess whether laboratory work during pregnancy increases the risk of adverse pregnancy outcomes. METHODS: The 1990-2006 Finnish Medical Birth Registry was used to identify all singleton newborns of all Finnish laboratory workers (n = 5425) and those of teachers (n = 21,438) as the reference population. The main outcomes were sexual differentiation (female gender), low birth weight, high birth weight, preterm delivery, post-term delivery, small-for-gestational age (SGA), large-for gestational age and perinatal death. The generalized estimating equation (GEE) analysis was used to estimate odds ratios (ORs) adjusted for maternal age, parity, marital status and maternal smoking during pregnancy. RESULTS: In the GEE analysis, the risk of low birth weight (adjusted OR: 1.27, 95% CI: 1.08-1.45) and SGA (adjusted OR: 1.27, 95% CI: 1.02-1.52) was higher in laboratory workers than in teachers. Correspondingly the prevalence of high birth weight (> or = 4000 g) was lower in newborns of laboratory workers (adjusted OR: 0.90, 95% CI: 0.83 0.98). The prevalence of post-term deliveries was close to being significantly higher among newborns of laboratory workers (adjusted OR: 1.16, 95% CI: 1.00 1.31). CONCLUSIONS: This large population-based study provides evidence that laboratory work may be associated with reduced foetal growth. PMID- 20308260 TI - Exogenous lipoid pneumonia caused by paraffin in an amateur fire breather. AB - BACKGROUND: Paraffin has characteristics that make it popular among fire breathers. AIMS: To describe a case of paraffin-induced lipoid pneumonia in a fire breather. METHODS: The patient was evaluated clinically in relation to his occupational history. RESULTS: A 32-year-old man presented with dyspnoea, tachypnoea and non-productive cough of 2 h duration that started immediately following an attempt to blow fire using paraffin as the volatile substance. He was discharged from the emergency ward but returned the next day presenting again with dyspnoea accompanied by mid-sternal pain, fever (38.1 degrees C) and leucocytosis. Chest radiography showed perihilar punctuate infiltrations. A diagnosis of exogenous lipoid pneumonia caused by paraffin was made, and the patient was treated, with full recovery within a week. CONCLUSIONS: Fire breathers must be viewed as a population at risk of paraffin-induced lipoid pneumonia. PMID- 20308261 TI - Surveillance of Australian workplace Based Respiratory Events (SABRE) in New South Wales. AB - BACKGROUND: The Surveillance of Australian workplace Based Respiratory Events (SABRE) New South Wales (NSW) scheme is a voluntary notification scheme established to determine the incidence of occupational lung diseases in NSW Australia. AIMS: Data presented in this paper summarize the last 7 years of reporting to SABRE (June 2001 to December 2008). METHODS: Every 2 months, participating occupational physicians, respiratory physicians and general practitioners (accredited by the NSW WorkCover Authority) reported new cases of occupational lung disease seen in their practices. Data collected include gender, age, causal agent and the occupations and industries believed responsible. Estimated incidence was calculated for each disease. RESULTS: Three thousand six hundred and fifty-four cases were notified to the scheme, consisting of 3856 diagnoses. Most of the cases were males (76%). Pleural plaques [1218 (28%)] were the most frequently reported condition, followed by mesothelioma [919 (24%)]. Silicosis [90 (2%)] and occupational asthma [OA; 89 (2%)] were the most frequently reported non-asbestos-related diseases. Estimated rates for mesothelioma, diffuse pleural thickening (DPT) and OA were 83, 83 and 5 cases per million employed males per year, respectively. Trades such as carpenters and electricians associated with the building industry, electricity supply and asbestos product manufacture were the most common occupations and industries reported. CONCLUSIONS: Asbestos-related diseases are the most frequently reported conditions to SABRE NSW. The very low incidence of OA for NSW most likely reflects under-diagnosis as well as under-reporting. Occupational lung disease is still occurring in NSW despite current preventative strategies. The SABRE scheme currently provides the only available information in this area. PMID- 20308262 TI - Obesity and sickness absence: results from the CHAP study. AB - BACKGROUND: Obesity is an increasing public health problem. A small number of studies have examined the relationship between obesity and sickness absence, with mixed results, particularly regarding short-term sickness absence. AIMS: To determine if obesity is associated with short- and long-term sickness absence and to investigate the mechanisms that may underlie any association. METHODS: Cross sectional (n = 1489) and prospective (n = 625) analyses were conducted on staff from London Underground Ltd. All participants underwent regular clinical examinations that involved their height and weight being measured, obesity related medical problems being diagnosed and psychiatric disorders being identified. The number of days taken for short- (<10 days in an episode) and long term sickness absence were recorded by managers on an electronic database. RESULTS: There was a positive linear association between employees' body mass index (BMI) and the number of days' work missed due to sickness absence on both cross-sectional and prospective analyses (P < 0.001). Obesity was a risk factor for both short- and long-term sickness absence. Obese individuals typically took an extra 4 days sick leave every year. The majority of the increased risk for long-term sickness absence appeared to be mediated via co-morbid chronic medical conditions. The excess short-term sickness absence was not explained by obesity related medical problems, psychiatric disorders or workplace factors. CONCLUSIONS: Obese employees take significantly more short- and long-term sickness absence than workers of a healthy weight. There is growing evidence to support employers becoming more involved in tackling obesity. PMID- 20308263 TI - Do patients undergoing lung biopsy need a postoperative chest drain at all? AB - A best evidence topic in thoracic surgery was written according to a structured protocol. The question addressed whether insertion of an intercostal chest drain prolongs the length of stay of patients undergoing lung biopsy. Altogether 210 papers were found using the reported search, of which 10 represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated. We conclude that where an intraoperative check reveals no air leak, chest drain should be avoided if possible in order to discharge patients earlier. Where chest drain is used following video-assisted thoracoscopic surgery lung biopsy, early removal results in reduced pain and earlier discharge. Four studies advocate early chest tube removal, allowing discharge of 95% within 24 h in one study, reduced hospital stay from 3.9+/-2.1 days to 2+/-1 days (P=0.001) in another, and a median stay of 1.2 days (range 0-7 days) in a third. Removal of chest drain within 1 h of the operation was possible in 92% of patients (one study), significantly reducing pain (P=0.03, P=0.005; two studies) and postoperative complications (P=0.01; one study) compared with conventional treatment. Five studies in which patients were managed without chest drain following intraoperative air leak checks, reduced hospital stay vs. conventional management (two studies; 2 vs. 3, P<0.001, 1 vs. 3, P<0.01) but results in no difference in complication rates (three studies: pneumothoraces requiring chest drain; 2 vs. 2, P=non-significant; 0 vs. 0; 0 vs. 0) or pain score (two studies; 0.77 vs. 0.76, P=0.894; 5 vs. 5, P=0.81). PMID- 20308264 TI - Correlation of computed tomography densitometry and pathological grading of emphysema with the variation of respiratory function after lobectomy for lung cancer. AB - The presence of emphysema may lead to an underestimation of postoperative respiratory function after lobectomy when evaluated by standard functional assessment. The aim of the study was to assess the correlation between computed tomography (CT) densitometry, pathological grading of emphysema and variation of pulmonary function after lobectomy for lung cancer. Forty-one patients entered the study. Respiratory function was assessed preoperatively and after a mean period of 4.04 months following surgery. Postoperative function remained unchanged or increased after surgery in nine patients (Group A). In the remaining 32 patients (Group B) postoperative function was reduced after surgery. Preoperative forced expiratory volume in 1 s (FEV(1))% was 68.5+/-13.1% in Group A and 91.7+/-21.0% in Group B. CT densitometry of the lobe to be resected was 877.8+/-57.6 HU in Group A and -827.5+/-64.4 HU in Group B. Pathological grading of emphysema of the resected lobe (range 0-10) was 4.1+/-2.2 in Group A and 3.1+/ 1.2 in Group B. A significant correlation was observed (Spearman rank correlation) between the variation of FEV(1) and preoperative FEV(1) (P=0.003; r= 0.455), CT quantitative assessment (P=0.036; r=-0.430) and pathological grading (P=0.008; r=0.673). Patients with a higher degree of emphysema had a lower reduction of respiratory function after lobectomy and CT densitometry and pathological grading of emphysema correlated with the variation in respiratory function. PMID- 20308265 TI - Pneumonectomy for lung cancer over the age of 75 years: is it worthwhile? AB - The objective of the study was to evaluate the outcome in elderly patients (>75 years) submitted to pneumonectomy for lung cancer. Records of 40 elderly patients, who underwent pneumonectomy at our Institution from 1990 to 2008, were retrospectively reviewed. This group was compared with 289 younger patients submitted to pneumonectomy in the same period. In the older group median age was 77 years (range 75-84 years), 16 were right-side procedures. In the younger group median age was 62 years (range 24-74 years), 114 were right-sided procedures. The overall mortality rate was 7.5% and 6.2% in the older and younger groups, respectively (P=0.75); morbidity rate was 35.1% and 17.7% (P=0.01) and five-year survival rate was 32% and 30%, respectively (P=0.85). Right-sided procedures (P=0.0006) were associated with higher risk of mortality and age over 75 years (P=0.01) with increased risk of morbidity; pathological stage was the only predictor of five-year survival. Pneumonectomy appears to be justified even in patients older than 75 years, because short- and long-term outcomes can be acceptable and comparable with those of younger patients. Advanced age alone does not justify denying curative resection of lung cancer, but right-sided procedures require a careful pre- and postoperative approach. PMID- 20308266 TI - Does ABO-incompatible and ABO-compatible neonatal heart transplant have equivalent survival? AB - A best evidence topic (BET) in cardiac surgery was written according to a structured protocol. The question addressed was whether ABO-incompatible (ABO-I) heart transplant recipients have a similar survival rate as an ABO-compatible (ABO-C) transplant in the pediatric population <1 year of age. Altogether more than 112 papers were found using the reported search, of which 10 represented the best evidence to answer the clinical question. Generally, ABO-I transplantation has been associated with the neonatal population because of the relative immaturity of the immune system for the first year of life. In the BET the search term 'pediatric' was used as a method to ensure retrieval all relevant papers. However, the vast majority of the patients reviewed were <1 year of age with specific techniques undertaken to modulate preoperative, intraoperative and postoperative isohemagglutinin titer levels with rejection monitoring. Therefore, the BET conclusions should not be applied to the pediatric group as a broad age classification. Two large series are of particular interest. Patel et al. reviewed all primary heart transplantation recipients < or =1 year of age in the United Network for Organ Sharing/Organ Procurement and Transplantation Network (UNOS/OPTN) registry (ABO-I=35 vs. ABO-C=556). There was no difference in 30-day mortality (ABO-I=5.9% vs. ABO-C=8.8%; P=0.55); one-year mortality (ABO-I=16.6% vs. ABO-C=14.7%; P=0.77); graft rejection (ABO-I=1 vs. ABO-C=0); and graft failure (ABO-I=24% vs. ABO-C=24%; P>0.99). Three-year Kaplan-Meier survival was 70% (P=0.85). Propensity score adjusted analysis did not implicate ABO-I as a predictor of mortality [hazard ratio (HR)=3.6, confidence interval (CI): 0.2 49.0; P=0.33]. The ABO-I group demonstrated an increased need for pacemaker (ABO I=3.1% vs. ABO-C=0.4%; P=0.03) and higher stroke rate (ABO-I=12.9% vs. ABO C=1.3%; P<0.0001). Dipchand et al. published the results of the Toronto cohort from 1992 to 2006 (ABO-I=16 vs. ABO-C=38). The median age at transplantation (ABO I=88 days vs. ABO-C=84 days; P=0.82) and the number of neonatal transplant recipients (ABO-I=17% vs. ABO-C=22%; P=0.59) was similar. The freedom from post transplantation death or retransplantation was equivalent at one year (ABO-I=77% vs. ABO-C=84%) and seven years (ABO-I=74% vs. ABO-C=74%; P=0.87). No significant difference was observed for the five-year freedom from: rejection (ABO-I=60% vs. ABO-C=45%; P=0.41); renal dysfunction (ABO-I=67% vs. ABO-C=72%; P=0.70); allograft vasculopathy (ABO-I=87% vs. ABO-C=78%; P=0.45); and post transplantation lymphoproliferative disorder (PTLD) (ABO-I=87% vs. ABO-C=86%; P=0.93). We conclude that ABO-I transplantation is comparable to ABO-C transplantation, with several retrospective papers concluding there is no difference in mortality, morbidity or graft failure in the pediatric population <1 year of age. PMID- 20308268 TI - Cortical rim sign and acute renal infarction. PMID- 20308269 TI - Cholesterol microembolization syndrome: a complication of anticoagulant therapy. PMID- 20308270 TI - Association between parity and risk of suicide among parous women. AB - BACKGROUND: There are limited empirical data to support the theory of a protective effect of parenthood against suicide, as proposed by Durkheim in 1897. I conducted this study to examine whether there is an association between parity and risk of death from suicide among women. METHODS: The study cohort consisted of 1,292,462 women in Taiwan who had a first live birth between Jan. 1, 1978, and Dec. 31, 1987. The women were followed up from the date of their first birth to Dec. 31, 2007. Their vital status was ascertained by means of linking records with data from a computerized mortality database. Cox proportional hazard regression models were used to estimate hazard ratios of death from suicide associated with parity. RESULTS: There were 2252 deaths from suicide during 32 464 187 person-years of follow-up. Suicide-related mortality was 6.94 per 100,000 person-years. After adjustment for age at first birth, marital status, years of schooling and place of delivery, the adjusted hazard ratio was 0.61 (95% confidence interval [CI] 0.54-0.68) among women with two live births and 0.40 (95% CI 0.35-0.45) among those with three or more live births, compared with women who had one live birth. I observed a significantly decreasing trend in adjusted hazard ratios of suicide with increasing parity. INTERPRETATION: This study provides evidence to support Durkheim's hypothesis that parenthood confers a protective effect against suicide. PMID- 20308271 TI - Accuracy of patient-reported height loss and risk factors for height loss among postmenopausal women. AB - BACKGROUND: Since loss of height may indicate vertebral fracture, the accuracy of the information on height is relevant for clinical practice. We undertook this study to compare reported and measured loss of height among post-menopausal women in a primary care setting. We also analyzed the determinants of this height loss. METHODS: In an observational study conducted between December 2007 and May 2008, we asked 1779 randomly selected general practitioners to recruit the first five female patients who were more than 60 years of age, regardless of the reason for the consultation. Using a questionnaire, physicians collected data on demographic and clinical variables, history of osteoporosis and current anti-osteoporotic treatment. We used three assessments of height: tallest height in early adulthood recalled by the patient, estimated current height reported by the patient at the visit and current measured height. We defined loss of height as the difference between the patient's tallest recalled height and her current measured height. RESULTS: A total of 8610 patients were included in the analysis; the mean age was 70.9 (standard deviation [SD] 7.2) years. The mean loss of height was 4.5 cm. The mean current reported height was 2.1 (SD 2.5) cm lower than the tallest recalled height and 2.4 (SD 2.6) cm lower than the measured current height. The best predictors of a loss of height of 3 cm or more were age (odds ratio [OR] 1.09, 95% confidence interval [CI] 1.08-1.10), previous vertebral fracture (OR 1.49, 95% CI 1.16-1.91), previous nonvertebral fracture (OR 1.26, 95% CI 1.06-1.51), thoracic kyphosis (OR 2.07, 95% CI 1.69-2.55), scoliosis (OR 1.35, 95% CI 1.12 1.63), back pain (OR 1.22, 95% CI 1.07-1.39) and osteoporosis (OR 1.39, 95% CI 1.20-1.60). INTERPRETATION: Our study showed that the patients' estimated current height was not correct, with a mean difference of -2.5 cm from the current measured height. The mean height loss was 4.5 cm. Previous vertebral fracture and thoracic kyphosis were strong determinants of the height loss. PMID- 20308272 TI - Amalgamation triggers linguistic constitutional challenge. PMID- 20308273 TI - Stroke rehabilitation services inadequate, experts say. PMID- 20308274 TI - Veterans stepping forward for treatment of operational stress injuries. PMID- 20308275 TI - Memorial and Western are leaders in incorporating technology in med schools. PMID- 20308276 TI - Health care in Romania: fighting collapse. PMID- 20308277 TI - A large and a small hand. PMID- 20308278 TI - Accurate prediction of genetic values for complex traits by whole-genome resequencing. AB - Whole-genome resequencing technology has improved rapidly during recent years and is expected to improve further such that the sequencing of an entire human genome sequence for $1000 is within reach. Our main aim here is to use whole-genome sequence data for the prediction of genetic values of individuals for complex traits and to explore the accuracy of such predictions. This is relevant for the fields of plant and animal breeding and, in human genetics, for the prediction of an individual's risk for complex diseases. Here, population history and genomic architectures were simulated under the Wright-Fisher population and infinite sites mutation model, and prediction of genetic value was by the genomic selection approach, where a Bayesian nonlinear model was used to predict the effects of individual SNPs. The Bayesian model assumed a priori that only few SNPs are causative, i.e., have an effect different from zero. When using whole genome sequence data, accuracies of prediction of genetic value were >40% increased relative to the use of dense approximately 30K SNP chips. At equal high density, the inclusion of the causative mutations yielded an extra increase of accuracy of 2.5-3.7%. Predictions of genetic value remained accurate even when the training and evaluation data were 10 generations apart. Best linear unbiased prediction (BLUP) of SNP effects does not take full advantage of the genome sequence data, and nonlinear predictions, such as the Bayesian method used here, are needed to achieve maximum accuracy. On the basis of theoretical work, the results could be extended to more realistic genome and population sizes. PMID- 20308279 TI - Functional genomic identification of genes required for male gonadal differentiation in Caenorhabditis elegans. AB - The Caenorhabditis elegans somatic gonad develops from a four-cell primordium into a mature organ that differs dramatically between the sexes in overall morphology (two arms in hermaphrodites and one in males) and in the cell types comprising it. Gonadal development in C. elegans is well studied, but regulation of sexual differentiation, especially later in gonadal development, remains poorly elucidated. To identify genes involved in this process, we performed a genome-wide RNAi screen using sex-specifically expressed gonadal GFP reporters. This screen identified several phenotypic classes, including approximately 70 genes whose depletion feminized male gonadal cells. Among the genes required for male cell fate specification are Wnt/beta-catenin pathway members, cell cycle regulators, and genes required for mitotic spindle function and cytokinesis. We find that a Wnt/beta-catenin pathway independent of extracellular Wnt ligand is essential for asymmetric cell divisions and male differentiation during gonadal development in larvae. We also find that the cell cycle regulators cdk-1 and cyb 3 and the spindle/cytokinesis regulator zen-4 are required for Wnt/beta-catenin pathway activity in the developing gonad. After sex is determined in the gonadal primordium the global sex determination pathway is dispensable for gonadal sexual fate, suggesting that male cell fates are promoted and maintained independently of the global pathway during this period. PMID- 20308280 TI - A strand invasion 3' polymerization intermediate of mammalian homologous recombination. AB - Initial events in double-strand break repair by homologous recombination in vivo involve homology searching, 3' strand invasion, and new DNA synthesis. While studies in yeast have contributed much to our knowledge of these processes, in comparison, little is known of the early events in the integrated mammalian system. In this study, a sensitive PCR procedure was developed to detect the new DNA synthesis that accompanies mammalian homologous recombination. The test system exploits a well-characterized gene targeting assay in which the transfected vector bears a gap in the region of homology to the single-copy chromosomal immunoglobulin mu heavy chain gene in mouse hybridoma cells. New DNA synthesis primed by invading 3' vector ends copies chromosomal mu-gene template sequences excluded by the vector-borne double-stranded gap. Following electroporation, specific 3' extension products from each vector end are detected with rapid kinetics: they appear after 0.5 hr, peak at 3-6 hr, and then decline, likely as a result of the combined effects of susceptibility to degradation and cell division. New DNA synthesis from each vector 3' end extends at least approximately 1000 nucleotides into the gapped region, but the efficiency declines markedly within the first approximately 200 nucleotides. Over this short distance, an average frequency of 3' extension for the two invading vector ends is approximately 0.007 events/vector backbone. DNA sequencing reveals precise copying of the cognate chromosomal mu-gene template. In unsynchronized cells, 3' extension is sensitive to aphidicolin supporting involvement of a replicative polymerase. Analysis suggests that the vast majority of 3' extensions reside on linear plasmid molecules. PMID- 20308285 TI - Physicians lead reform. PMID- 20308281 TI - Caenorhabditis elegans fibroblast growth factor receptor signaling can occur independently of the multi-substrate adaptor FRS2. AB - The components of receptor tyrosine kinase signaling complexes help to define the specificity of the effects of their activation. The Caenorhabditis elegans fibroblast growth factor receptor (FGFR), EGL-15, regulates a number of processes, including sex myoblast (SM) migration guidance and fluid homeostasis, both of which require a Grb2/Sos/Ras cassette of signaling components. Here we show that SEM-5/Grb2 can bind directly to EGL-15 to mediate SM chemoattraction. A yeast two-hybrid screen identified SEM-5 as able to interact with the carboxy terminal domain (CTD) of EGL-15, a domain that is specifically required for SM chemoattraction. This interaction requires the SEM-5 SH2-binding motifs present in the CTD (Y(1009) and Y(1087)), and these sites are required for the CTD role of EGL-15 in SM chemoattraction. SEM-5, but not the SEM-5 binding sites located in the CTD, is required for the fluid homeostasis function of EGL-15, indicating that SEM-5 can link to EGL-15 through an alternative mechanism. The multi substrate adaptor protein FRS2 serves to link vertebrate FGFRs to Grb2. In C. elegans, an FRS2-like gene, rog-1, functions upstream of a Ras/MAPK pathway for oocyte maturation but is not required for EGL-15 function. Thus, unlike the vertebrate FGFRs, which require the multi-substrate adaptor FRS2 to recruit Grb2, EGL-15 can recruit SEM-5/Grb2 directly. PMID- 20308287 TI - Defining high risk. PMID- 20308288 TI - ADHD and obesity. PMID- 20308289 TI - Auditory processing disorder and speech perception problems in noise: finding the underlying origin. AB - PURPOSE: A hallmark listening problem of individuals presenting with auditory processing disorder (APD) is their poor recognition of speech in noise. The underlying perceptual problem of the listening difficulties in unfavorable listening conditions is unknown. The objective of this article was to demonstrate theoretically how to determine whether the speech recognition problems are related to an auditory dysfunction, a language-based dysfunction, or a combination of both. METHOD: Tests such as the Speech Perception in Noise (SPIN) test allow the exploration of the auditory and language-based functions involved in speech perception in noise, which is not possible with most other speech-in noise tests. Psychometric functions illustrating results from hypothetical groups of individuals with APD on the SPIN test are presented. This approach makes it possible to postulate about the origin of the speech perception problems in noise. CONCLUSION: APD is a complex and heterogeneous disorder for which the underlying deficit is currently unclear. Because of their design, SPIN-like tests can potentially be used to identify the nature of the deficits underlying problems with speech perception in noise for this population. A better understanding of the difficulties with speech perception in noise experienced by many listeners with APD should lead to more efficient intervention programs. PMID- 20308290 TI - Within-treatment factors as predictors of outcomes following conversational recasting. AB - PURPOSE: Although conversational recasting has been a generally successful treatment approach, the precise factors that influence children's learning through recasts are not yet understood. In this study, we examined details of the relationship between child utterance and clinician utterance that seemed likely to influence learning. METHOD: Three measures were calculated from transcripts of recasting sessions with 17 preschoolers with specific language impairment. In all sessions, 3rd person singular -s served as the target. The measures of interest were the frequency of recasts following child utterances that were prompted by clinicians, the frequency of clinicians' recasts of subjectless sentences, and the frequency of clinicians' noncorrective recasts. We assessed the short-term and long-term predictive value of these measures through regression analyses. RESULTS: Noncorrective recasts proved to be a positive predictor of short- and long-term gains in the use of the target form. Recasts of subjectless sentences were associated with poorer outcomes, though their contribution was relatively small. CONCLUSIONS: The nature of learning that takes place varies according to the relationship between child and clinician utterances during the recasting process. These variations have implications for clinical practice and for how learning through recasting is characterized. PMID- 20308291 TI - Interactions of Encephalitozoon cuniculi polar tube proteins. AB - Microsporidia are eukaryotic, obligate intracellular organisms defined by small spores that contain a single invasion organelle, the polar tube, which coils around the interior of the spore. When these parasites infect host cells, the polar tube is discharged from the anterior pole of the spore, pierces the cell, and transfers sporoplasm into the cytoplasm of the host. Three polar tube proteins (PTP1, PTP2, and PTP3) have been identified in this structure. The interactions of these proteins in the assembly and function of the polar tube are not known. This study was undertaken to examine the protein interactions of the Encephalitozoon cuniculi polar tube proteins (EcPTPs). Immunofluorescence and immunoelectron microscopy confirmed the colocalization of EcPTP1, EcPTP2, and EcPTP3 to the polar tube. Experiments using cross-linkers indicated that EcPTP1, EcPTP2, and EcPTP3 form a complex in the polar tube, which was confirmed by immunoprecipitation using EcPTP1 antiserum. Yeast two-hybrid analysis revealed that full-length EcPTP1, EcPTP2, and EcPTP3 interact with each other in vivo. Both the N and C termini of EcPTP1 were involved in these interactions, but the central region of this protein, which contains a repetitive motif, was not. Further studies of polar tube proteins and their structural interactions may help elucidate the formation of the polar tube during the invasion process. PMID- 20308292 TI - Lack of interleukin-12 in p40-deficient mice leads to poor CD8+ T-cell immunity against Encephalitozoon cuniculi infection. AB - A CD8(+) T-cell response is critical for protection against Encephalitozoon cuniculi infection. However, the factors responsible for the generation of CD8(+) T-cell immunity during E. cuniculi infection and the cytokines involved in this process have not been identified. In the present study, we demonstrated that p40 deficient animals, which are unable to produce interleukin-12 (IL-12), have a serious defect in expansion of the CD8(+) T-cell response which compromises the survival of an infected host. Adoptive transfer of CD8(+) T cells from immunocompetent donors protected SCID mice infected with E. cuniculi, whereas administration of CD8(+) T cells from p40(-/-) mice failed to protect infected SCID mice. In vitro dendritic cell (DC) cultures from knockout mice pulsed with E. cuniculi spores were unable to develop a robust CD8(+) T-cell immune response. Addition of exogenous IL-12 or transfer of CD8(+) T cells that were initially primed with DC from p40(-/-) animals to DC cultures from immunocompetent mice (directly or via transwells) led to optimal expansion of these cells. This IL-12 mediated reinstatement of CD8(+) T-effector immunity was independent of gamma interferon (IFN-gamma) as addition of antibody to the cultures failed to have an effect. These studies demonstrated that IL-12 plays a predominant role in the expansion of effector CD8(+) T-cell immunity against E. cuniculi, which is critical for host survival. These findings are very important for understanding the protective immune mechanisms needed to protect an immunocompromised host against an opportunistic infection and can be extended to other microsporidial pathogens. PMID- 20308293 TI - Trimer stability of YadA is critical for virulence of Yersinia enterocolitica. AB - Yersinia adhesin A (YadA) is a trimeric autotransporter adhesin with multiple functions in host-pathogen interactions. The aim of this study was to dissect the virulence functions promoted by YadA in vitro and in vivo. To accomplish this, we generated Yersinia enterocolitica O:8 mutants expressing point mutations in YadA G389, a highly conserved residue in the membrane anchor of YadA, and analyzed their impact on YadA expression and virulence functions. We found that point mutations of YadA G389 led to impaired transport, stability, and surface display of YadA. YadA G389A and G389S mutants showed comparable YadA surface expression, autoagglutination, and adhesion to those of wild-type YadA but displayed reduced trimer stability and complement resistance in vitro and were 10- to 1,000-fold attenuated in experimental Y. enterocolitica infection in mice. The G389T, G389N, and G389H mutants lost trimer stability, exhibited strongly reduced surface display, autoagglutination, adhesion properties, and complement resistance, and were avirulent (>10,000-fold attenuation) in mice. Our data demonstrate that G389 is a critical residue of YadA, required for optimal trimer stability, transport, surface display, and serum resistance. We also show that stable trimeric YadA protein is essential for virulence of Y. enterocolitica. PMID- 20308294 TI - Functional characterization of the IlpA protein of Vibrio vulnificus as an adhesin and its role in bacterial pathogenesis. AB - Vibrio vulnificus is a Gram-negative bacterium that causes a fatal septicemia. One of its virulence factors is a membrane-bound lipoprotein, IlpA, which can induce cytokine production in human immune cells. In the present study, the role of IlpA as an adhesion molecule was investigated. An ilpA-deleted V. vulnificus mutant showed significantly decreased adherence to INT-407 human intestinal epithelial cells, which in turn resulted in reduced cytotoxicity. The DeltailpA mutant recovered the adherence ability of the wild type by complementation in trans with the intact ilpA gene. In addition, pretreatment of V. vulnificus with anti-IlpA polyclonal antibodies resulted in a significant reduction of bacterial adherence. To localize the domain of IlpA required for cytoadherence, three truncated recombinant IlpA polypeptides were constructed and tested for the ability to adhere to human cells by a ligand-binding immunoblot assay and fluorescence microscopy. The polypeptide containing the carboxy (C)-terminal hydrophilic domain exhibited direct binding to INT-407 cells. Therefore, the C terminal domain of IlpA allows this protein to be an adhesion molecule of V. vulnificus. PMID- 20308295 TI - Zebrafish as a model host for Candida albicans infection. AB - In this work, the zebrafish model organism was developed to obtain a minivertebrate host system for a Candida albicans infection study. We demonstrated that C. albicans can colonize and invade zebrafish at multiple anatomical sites and kill the fish in a dose-dependent manner. Inside zebrafish, we monitored the progression of the C. albicans yeast-to-hypha transition by tracking morphogenesis, and we monitored the corresponding gene expression of the pathogen and the early host immune response. We performed a zebrafish survival assay with different C. albicans strains (SC5314, ATCC 10231, an hgc1 mutant, and a cph1/efg1 double mutant) to determine each strain's virulence, and the results were similar to findings reported in previous mouse model studies. Finally, using zebrafish embryos, we monitored C. albicans infection and visualized the interaction between pathogen and host myelomonocytic cells in vivo. Taken together, the results of this work demonstrate that zebrafish can be a useful host model to study C. albicans pathogenesis, and they highlight the advantages of using the zebrafish model in future invasive fungal research. PMID- 20308296 TI - Fine-tuning synthesis of Yersinia pestis LcrV from runaway-like replication balanced-lethal plasmid in a Salmonella enterica serovar typhimurium vaccine induces protection against a lethal Y. pestis challenge in mice. AB - A balanced-lethal plasmid expression system that switches from low-copy-number to runaway-like high-copy-number replication (pYA4534) was constructed for the regulated delayed in vivo synthesis of heterologous antigens by vaccine strains. This is an antibiotic resistance-free maintenance system containing the asdA gene (essential for peptidoglycan synthesis) as a selectable marker to complement the lethal chromosomal DeltaasdA allele in live recombinant attenuated Salmonella vaccines (RASVs) such as Salmonella enterica serovar Typhimurium strain chi9447. pYA4534 harbors two origins of replication, pSC101 and pUC (low and high copy numbers, respectively). The pUC replication origin is controlled by a genetic switch formed by the operator/promoter of the P22 cro gene (O/P(cro)) (P(R)), which is negatively regulated by an arabinose-inducible P22 c2 gene located on both the plasmid and the chromosome (araC P(BAD) c2). The absence of arabinose, which is unavailable in vivo, triggers replication to a high-copy-number plasmid state. To validate these vector attributes, the Yersinia pestis virulence antigen LcrV was used to develop a vaccine against plague. An lcrV sequence encoding amino acids 131 to 326 (LcrV196) was optimized for expression in Salmonella, flanked with nucleotide sequences encoding the signal peptide (SS) and the carboxy-terminal domain (CT) of beta-lactamase, and cloned into pYA4534 under the control of the P(trc) promoter to generate plasmid pYA4535. Our results indicate that the live Salmonella vaccine strain chi9447 harboring pYA4535 efficiently stimulated a mixed Th1/Th2 immune response that protected mice against lethal challenge with Y. pestis strain CO92 introduced through either the intranasal or subcutaneous route. PMID- 20308297 TI - Genome sequencing of recent clinical Chlamydia trachomatis strains identifies loci associated with tissue tropism and regions of apparent recombination. AB - The human pathogen Chlamydia trachomatis exists as multiple serovariants that have distinct organotropisms for different tissue sites. Culture and epidemiologic data have demonstrated that serovar G is more prevalent, while serovar E is less prevalent, for rectal isolates from men having sex with men (MSM). The relative prevalence of these serovars is the opposite for isolates from female cervical infections. In contrast, the prevalence of serovar J isolates is approximately the same at the different tissue sites, and these isolates are the only C-class strains that are routinely cultured from MSM populations. These correlations led us to hypothesize that polymorphisms in open reading frame (ORF) sequences correlate with the different tissue tropisms of these serovars. To explore this possibility, we sequenced and compared the genomes of clinical anorectal and cervical isolates belonging to serovars E, G, and J and compared these genomes with each other, as well as with a set of previously sequenced genomes. We then used PCR- and restriction digestion-based genotyping assays performed with a large collection of recent clinical isolates to show that polymorphisms in ORFs CT144, CT154, and CT326 were highly associated with rectal tropism in serovar G isolates and that polymorphisms in CT869 and CT870 were associated with tissue tropism across all serovars tested. The genome sequences collected were also used to identify regions of likely recombination in recent clinical strains. This work demonstrated that whole-genome sequencing along with comparative genomics is an effective approach for discovering variable loci in Chlamydia spp. that are associated with clinical presentation. PMID- 20308298 TI - Modulation of allergic airway inflammation by the oral pathogen Porphyromonas gingivalis. AB - Accumulating evidence suggests that bacteria associated with periodontal disease may exert systemic immunomodulatory effects. Although the improvement in oral hygiene practices in recent decades correlates with the increased incidence of asthma in developed nations, it is not known whether diseases of the respiratory system might be influenced by the presence of oral pathogens. The present study sought to determine whether subcutaneous infection with the anaerobic oral pathogen Porphyromonas gingivalis exerts a regulatory effect on allergic airway inflammation. BALB/c mice sensitized and subsequently challenged with ovalbumin exhibited airway hyperresponsiveness to methacholine aerosol and increased airway inflammatory cell influx and Th2 cytokine (interleukin-4 [IL-4], IL-5, and IL-13) content relative to those in nonallergic controls. Airway inflammatory cell and cytokine contents were significantly reduced by establishment of a subcutaneous infection with P. gingivalis prior to allergen sensitization, whereas serum levels of ovalbumin-specific IgE and airway responsiveness were not altered. Conversely, subcutaneous infection initiated after allergen sensitization did not alter inflammatory end points but did reduce airway responsiveness in spite of increased serum IgE levels. These data provide the first direct evidence of a regulatory effect of an oral pathogen on allergic airway inflammation and responsiveness. Furthermore, a temporal importance of the establishment of infection relative to allergen sensitization is demonstrated for allergic outcomes. PMID- 20308299 TI - AdpC is a Prevotella intermedia 17 leucine-rich repeat internalin-like protein. AB - The oral bacterium Prevotella intermedia attaches to and invades gingival epithelial cells, fibroblasts, and endothelial cells. Several genes encoding proteins that mediate both the adhesion and invasion processes are carried on the genome of this bacterium. Here, we characterized one such protein, AdpC, belonging to the leucine-rich repeat (LRR) protein family. Bioinformatics analysis revealed that this protein shares similarity with the Treponema pallidum LRR (LRR(TP)) family of proteins and contains six LRRs. Despite the absence of a signal peptide, this protein is localized on the bacterial outer membrane, indicating that it is transported through an atypical secretion mechanism. The recombinant form of this protein (rAdpC) was shown to bind fibrinogen. In addition, the heterologous host strain Escherichia coli BL21 expressing rAdpC (V2846) invaded fibroblast NIH 3T3 cells at a 40-fold-higher frequency than control E. coli BL21 cells expressing a sham P. intermedia 17 protein. Although similar results were obtained by using human umbilical vein endothelial cells (HUVECs), only a 3-fold-increased invasion of V2846 into oral epithelial HN4 cells was observed. Thus, AdpC-mediated invasion is cell specific. This work demonstrated that AdpC is an important invasin protein of P. intermedia 17. PMID- 20308300 TI - Probiotic colonization of the adherent mucus layer of HT29MTXE12 cells attenuates Campylobacter jejuni virulence properties. AB - The HT29MTXE12 (E12) cell line harbors an adherent mucus layer, providing a novel technique to model mucosal infection in vitro. In this study, we have characterized the interaction of Campylobacter jejuni with the E12 cell line and exploited its unique mucus layer to examine the potential efficacy of probiotic treatment to attenuate C. jejuni virulence properties. C. jejuni 81-176 colonized and reproduced in E12 mucus. Adhesion to and internalization of C. jejuni were enhanced in E12 cells harboring mucus compared to parental cells without mucus. Translocation of C. jejuni occurred at early time points following infection. C. jejuni aligned with tight junctions and colocalized with the tight junction protein occludin, suggesting a paracellular route of translocation. Probiotic strains Lactobacillus rhamnosus R0011, Lactobacillus helveticus R0052, Lactobacillus salivarius AH102, Bifidobacterium longum AH1205, a commercial combination of L. rhamnosus R0011 and L. helveticus R0052 (Lacidofil), and a cocktail consisting of L. rhamnosus, L. helveticus, and L. salivarius (RhHeSa) colonized E12 mucus and bound to underlying cells. Probiotics attenuated C. jejuni association with and internalization into E12 cells and translocation to the basolateral medium of transwells. Live bacteria and prolonged precolonization of E12 cells with probiotics were necessary for probiotic action. These results demonstrate the potential for E12 cells as a model of mucosal pathogenesis and provide a rationale for the further investigation of probiotics as prophylaxis against human campylobacteriosis. PMID- 20308301 TI - Distinct physiologic and inflammatory responses elicited in baboons after challenge with Shiga toxin type 1 or 2 from enterohemorrhagic Escherichia coli. AB - Shiga toxin-producing Escherichia coli is a principal source of regional outbreaks of bloody diarrhea and hemolytic-uremic syndrome in the United States and worldwide. Primary bacterial virulence factors are Shiga toxin types 1 and 2 (Stx1 and Stx2), and we performed parallel analyses of the pathophysiologies elicited by the toxins in nonhuman primate models to identify shared and unique consequences of the toxemias. After a single intravenous challenge with purified Stx1 or Stx2, baboons (Papio) developed thrombocytopenia, anemia, and acute renal failure with loss of glomerular function, in a dose-dependent manner. Differences in the timing and magnitude of physiologic responses were observed between the toxins. The animals were more sensitive to Stx2, with mortality at lower doses, but Stx2-induced renal injury and mortality were delayed 2 to 3 days compared to those after Stx1 challenge. Multiplex analyses of plasma inflammatory cytokines revealed similarities (macrophage chemoattractant protein 1 [MCP-1] and tumor necrosis factor alpha [TNF-alpha]) and differences (interleukin-6 [IL-6] and granulocyte colony-stimulating factor [G-CSF]) elicited by the toxins with respect to the mediator induced and timing of the responses. Neither toxin induced detectable levels of plasma TNF-alpha. To our knowledge, this is the first time that the in vivo consequences of the toxins have been compared in a parallel and reproducible manner in nonhuman primates, and the data show similarities to patient observations. The availability of experimental nonhuman primate models for Stx toxemias provides a reproducible platform for testing antitoxin compounds and immunotherapeutics with outcome criteria that have clinical meaning. PMID- 20308302 TI - Role of excessive inflammatory response to Stenotrophomonas maltophilia lung infection in DBA/2 mice and implications for cystic fibrosis. AB - Stenotrophomonas maltophilia is a pathogen that causes infections mainly in immunocompromised patients. Despite increased S. maltophilia isolation from respiratory specimens of patients with cystic fibrosis (CF), the real contribution of the microorganism to CF pathogenesis still needs to be clarified. The aim of the present study was to evaluate the pathogenic role of S. maltophilia in CF patients by using a model of acute respiratory infection in DBA/2 mice following a single exposure to aerosolized bacteria. The pulmonary bacterial load was stable until day 3 and then decreased significantly from day 3 through day 14, when the bacterial load became undetectable in all infected mice. Infection disseminated in most mice, although at a very low level. Severe effects (swollen lungs, large atelectasis, pleural adhesion, and hemorrhages) of lung pathology were observed on days 3, 7, and 14. The clearance of S. maltophilia observed in DBA/2 mouse lungs was clearly associated with an early and intense bronchial and alveolar inflammatory response, which is mediated primarily by neutrophils. Significantly higher levels of interleukin-1beta (IL-1beta), IL-6, IL-12, gamma interferon (IFN-gamma), tumor necrosis factor alpha (TNF-alpha), GROalpha/KC, MCP-1/JE, MCP-5, macrophage inflammatory protein 1alpha (MIP 1alpha), MIP-2, and TARC were observed in infected mice on day 1 with respect to controls. Excessive pulmonary infection and inflammation caused systemic effects, manifested by weight loss, and finally caused a high mortality rate. Taken together, our results show that S. maltophilia is not just a bystander in CF patients but has the potential to contribute to the inflammatory process that compromises respiratory function. PMID- 20308303 TI - Association of pathogen strain-specific gene transcription and transmission efficiency phenotype of Anaplasma marginale. AB - Efficient transmission of pathogens by an arthropod vector is influenced by the ability of the pathogen to replicate and develop infectiousness within the arthropod host. While the basic life cycle of development within and transmission from the arthropod vector are known for many bacterial and protozoan pathogens, the determinants of transmission efficiency are largely unknown and represent a significant gap in our knowledge. The St. Maries strain of Anaplasma marginale is a high-transmission-efficiency strain that replicates to a high titer in the tick salivary gland and can be transmitted by <10 ticks. In contrast, A. marginale subsp. centrale (Israel vaccine strain) has an identical life cycle but replicates to a significantly lower level in the salivary gland, with transmission requiring >30-fold more ticks. We hypothesized that strain-specific genes expressed in the tick salivary gland at the time of transmission are linked to the differences in the transmission efficiency phenotype. Using both annotation-dependent and -independent analyses of the complete genome sequences, we identified 58 strain-specific genes. These genes most likely represent divergence from common ancestral genes in one or both strains based on analysis of synteny and lack of statistical support for acquisition as islands by lateral gene transfer. Twenty of the St. Maries strain-specific genes and 16 of the strain-specific genes in the Israel strain were transcribed in the tick salivary gland at the time of transmission. Although associated with the transmission phenotype, the expression levels of strain-specific genes were equal to or less than the expression levels in infected erythrocytes in the mammalian host, suggesting that function is not limited to salivary gland colonization. PMID- 20308304 TI - Potent neutralization of staphylococcal enterotoxin B by synergistic action of chimeric antibodies. AB - Staphylococcal enterotoxin B (SEB), a shock-inducing exotoxin synthesized by Staphylococcus aureus, is an important cause of food poisoning and is a class B bioterrorism agent. SEB mediates antigen-independent activation of a major subset of the T-cell population by cross-linking T-cell receptors (TCRs) with class II major histocompatibility complex (MHC-II) molecules of antigen-presenting cells, resulting in the induction of antigen independent proliferation and cytokine secretion by a significant fraction of the T-cell population. Neutralizing antibodies inhibit SEB-mediated T-cell activation by blocking the toxin's interaction with the TCR or MHC-II and provide protection against the debilitating effects of this superantigen. We derived and searched a set of monoclonal mouse anti-SEB antibodies to identify neutralizing anti-SEB antibodies that bind to different sites on the toxin. A pair of non-cross-reactive, neutralizing anti-SEB monoclonal antibodies (MAbs) was found, and a combination of these antibodies inhibited SEB-induced T-cell proliferation in a synergistic rather than merely additive manner. In order to engineer antibodies more suitable than mouse MAbs for use in humans, the genes encoding the VL and VH gene segments of a synergistically acting pair of mouse MAbs were grafted, respectively, onto genes encoding the constant regions of human Igkappa and human IgG1, transfected into mammalian cells, and used to generate chimeric versions of these antibodies that had affinity and neutralization profiles essentially identical to their mouse counterparts. When tested in cultures of human peripheral blood mononuclear cells or splenocytes derived from HLA-DR3 transgenic mice, the chimeric human mouse antibodies synergistically neutralized SEB-induced T-cell activation and cytokine production. PMID- 20308305 TI - Inflammatory cytokine response to Bacillus anthracis peptidoglycan requires phagocytosis and lysosomal trafficking. AB - During advanced stages of inhalation anthrax, Bacillus anthracis accumulates at high levels in the bloodstream of the infected host. This bacteremia leads to sepsis during late-stage anthrax; however, the mechanisms through which B. anthracis-derived factors contribute to the pathology of infected hosts are poorly defined. Peptidoglycan, a major component of the cell wall of Gram positive bacteria, can provoke symptoms of sepsis in animal models. We have previously shown that peptidoglycan of B. anthracis can induce the production of proinflammatory cytokines by cells in human blood. Here, we show that biologically active peptidoglycan is shed from an active culture of encapsulated B. anthracis strain Ames in blood. Peptidoglycan is able to bind to surfaces of responding cells, and internalization of peptidoglycan is required for the production of inflammatory cytokines. We also show that the peptidoglycan traffics to lysosomes, and lysosomal function is required for cytokine production. We conclude that peptidoglycan of B. anthracis is initially bound by an unknown extracellular receptor, is phagocytosed, and traffics to lysosomes, where it is degraded to a product recognized by an intracellular receptor. Binding of the peptidoglycan product to the intracellular receptor causes a proinflammatory response. These findings provide new insight into the mechanism by which B. anthracis triggers sepsis during a critical stage of anthrax disease. PMID- 20308306 TI - Type IV secretion machinery promotes ton-independent intracellular survival of Neisseria gonorrhoeae within cervical epithelial cells. AB - Survival of Neisseria gonorrhoeae within host epithelial cells is expected to be important in the pathogenesis of gonococcal disease. We previously demonstrated that strain FA1090 derives iron from a host cell in a process that requires the Ton complex and a putative TonB-dependent transporter, TdfF. FA1090, however, lacks the gonococcal genetic island (GGI) that is present in the majority of strains. The GGI in strain MS11 has been partially characterized, and it encodes a type IV secretion system (T4SS) involved in DNA release. In this study we investigated the role of iron acquisition and GGI-encoded gene products in gonococcal survival within cervical epithelial cells. We demonstrated that intracellular survival of MS11 was dependent on acquisition of iron from the host cell, but unlike the findings for FA1090, expression of the Ton complex was not required. Survival was not dependent on a putative TonB-like protein encoded in the GGI but instead was directly linked to T4SS structural components in a manner independent of the ability to release or internalize DNA. These data suggest that expression of selected GGI-encoded open reading frames confers an advantage during cervical cell infection. This study provides the first link between expression of the T4SS apparatus and intracellular survival of gonococci. PMID- 20308309 TI - Immunotherapy for glioblastoma: a long and winding road. PMID- 20308310 TI - Allergy and inflammatory transcriptome is predominantly negatively correlated with CD133 expression in glioblastoma. AB - Allergies and the use of anti-inflammatory medication appear to be associated with reduced glioblastoma risk. However, these observations may merely reflect systemic immunosuppression induced by the tumor. To better understand the effect of this tumor on allergies and inflammation, we used CD133 mRNA expression as an indicator of tumor aggressiveness and systematically examined its relation to mRNA expression levels of 919 allergy- and inflammation-related genes in 142 glioblastoma tissue samples. We found that 69% of these genes are negatively correlated with CD133 expression including allergy-related (eg, interleukin [IL] 4R-alpha; Pearson correlation coefficient [r] = - 0.40; 95% confidence interval [CI] = - 0.53, -0.25) and immunoregulatory genes (eg, TGF-beta1; r = - 0.35; 95% CI = - 0.49, -0.20). Exceptions to this negative trend include the proinflammatory cytokine IL-17-beta (r = 0.22; 95% CI = 0.06, 0.37) and 2 IL-17 receptors. Also positively related to CD133 expression are NCAM-1 (r = 0.45; 95% CI = 0.31, 0.57) and PDGFR-alpha (r = 0.45; 95% CI = 0.30, 0.57). Previous literature suggests that NCAM-1(+) T cells infiltrate glioblastoma and may cause suppression of antitumor immunity, whereas PDGFR-alpha is involved in neurogenesis and amplified in glioblastoma. Ours is the first study to document down-regulation of the majority of allergy- and inflammation-related genes with glioblastoma progression. However, IL-17 and NCAM-1 may play proinflammatory and immunosuppressive roles, respectively, during the late stage of glioblastoma progression. Our findings suggest that immune function continues to change as the tumor progresses. PMID- 20308311 TI - Autophagy induced by valproic acid is associated with oxidative stress in glioma cell lines. AB - Autophagy represents an alternative tumor-suppressing mechanism that overcomes the dramatic resistance of malignant gliomas to radiotherapy and proapoptotic related chemotherapy. This study reports that valproic acid (VPA), a widely used anti-epilepsy drug, induces autophagy in glioma cells. Autophagy, crucial for VPA induced cell death, is independent of apoptosis, even though apoptotic machinery is proficient. Oxidative stress induced by VPA occurs upstream of autophagy. Oxidative stress also activates the extracellular signal-regulated kinase 1/2 (ERK1/2) pathway, whereas blocking this pathway inhibits autophagy and induces apoptosis. VPA-induced autophagy cannot be alleviated by inositol, suggesting a mechanism different from that for lithium. Moreover, VPA potentiates autophagic cell death, but not apoptosis, when combined with other autophagy inducers such as rapamycin, Ly294002, and temozolomide in glioma cells both in vitro and in vivo, which may warrant further investigation toward possible clinical application in patients with malignant gliomas. PMID- 20308312 TI - In vivo validation of MRI vessel caliber index measurement methods with intravital optical microscopy in a U87 mouse brain tumor model. AB - The vessel caliber index (VCI), a magnetic resonance imaging biomarker of the average blood vessel diameter, is increasingly being used as a tool for assessing tumor angiogenesis and response to antiangiogenic therapy. However, although the VCI has been correlated with histological vessel diameters, good quantitative agreement with histology has been lacking. In addition, no VCI validation studies have been performed in vivo where the structural deformations frequently associated with histological tissue preparation are not present. This study employs intravital optical microscopy (IVM) measurements of cerebral blood vessel diameters in a mouse orthotopic glioma model to provide the first such in vivo validation. Two VCI correlation models, both a linear and a 3/2-power dependence on the DeltaR2*/DeltaR2 ratio, were compared with the IVM data. The linear VCI model, determined from steady-state susceptibility contrast (SSC) images, was found to be in excellent quantitative agreement with the intravitally determined VCI for separate tumor size matched groups of mice. In addition, preliminary data indicate that the VCI is independent of whether a dynamic susceptibility contrast or SSC measurement method is used. PMID- 20308313 TI - Normal human monocytes exposed to glioma cells acquire myeloid-derived suppressor cell-like properties. AB - Glioblastoma patients are immunosuppressed, yet glioblastomas are highly infiltrated by monocytes/macrophages. Myeloid-derived suppressor cells (MDSC; immunosuppressive myeloid cells including monocytes) have been identified in other cancers and correlate with tumor burden. We hypothesized that glioblastoma exposure causes normal monocytes to assume an MDSC-like phenotype and that MDSC are increased in glioblastoma patients. Healthy donor human CD14(+) monocytes were cultured with human glioblastoma cell lines. Controls were cultured alone or with normal human astrocytes. After 48 hours, glioblastoma-conditioned monocytes (GCM) were purified using magnetic beads. GCM cytokine and costimulatory molecular expression, phagocytic ability, and ability to induce apoptosis in activated lymphocytes were assessed. The frequency of MDSC was assessed by flow cytometry in glioma patients' blood and in GCM in vitro. As predicted, GCM have immunosuppressive, MDSC-like features, including reduced CD14 (but not CD11b) expression, increased immunosuppressive interleukin-10, transforming growth factor-beta, and B7-H1 expression, decreased phagocytic ability, and increased ability to induce apoptosis in activated lymphocytes. Direct contact between monocytes and glioblastoma cells is necessary for complete induction of these effects. In keeping with our hypothesis, glioblastoma patients have increased circulating MDSC compared with normal donors and MDSC are increased in glioma conditioned monocytes in vitro. To our knowledge, this has not been reported previously. Although further study is needed to directly characterize their origin and function in glioblastoma patients, these results suggest that MDSC may be an important contributor to systemic immunosuppression and can be modeled in vitro by GCM. PMID- 20308314 TI - Morphologic and molecular characterization of ATRT xenografts adapted for orthotopic therapeutic testing. AB - Atypical teratoid rhabdoid tumor (ATRT) is a malignant tumor of the central nervous system that most commonly arises in young children. The aggressive growth and propensity for early dissemination throughout the neuraxis confers a dismal prognosis. Large clinical trials that could test new therapeutic agents are difficult to conduct due to the low incidence of this cancer. For this reason, high throughput preclinical testing with suitable animal models for ATRT would serve a critical need for identifying the most efficacious treatments. In response to this need, we have adapted ATRT cell lines for bioluminescence imaging (BLI) of intracranial (orthotopic) xenografts established in athymic mice. Our results indicate that following supratentorial or infratentorial injection in athymic mice, ATRT cells produce rapidly growing tumors, often with intraventricular spread or neuraxis dissemination. When established as orthotopic xenografts, the tumors predominantly display cells with a rhabdoid-like cellular morphology that show a spectrum of immunophenotypes similar to primary ATRT tumors. To demonstrate the feasibility of this orthotopic ATRT xenograft model for therapeutic testing with correlation to biomarker analysis, we examined the responses of luciferase-modified ATRT cells to temozolomide (TMZ). These xenografts, which highly express MGMT, are resistant to TMZ treatment when compared with an orthotopic glioblastoma xenograft that is MGMT deficient and responsive to TMZ. These data suggest that an orthotopic ATRT xenograft model, in which BLI is used for monitoring tumor growth and response to therapy, should contribute to the identification of effective therapeutics and regimens for treating this highly aggressive pediatric brain tumor. PMID- 20308315 TI - Intra-tumoral dendritic cells increase efficacy of peripheral vaccination by modulation of glioma microenvironment. AB - Pilot data showed that adding intratumoral (IT) injection of dendritic cells (DCs) prolongs survival of patients affected by glioblastoma multiforme (GBM) treated by subcutaneous (SC) delivery of DCs. Using a murine model resembling GBM, we investigated the immunological mechanisms underlying this effect. C57BL6/N mice received brain injections of GL261 glioma cells. Seven days later, mice were treated by 3 SC injections of DCs with or without 1 IT injection of DCs. DC maturation, induced by pulsing with GL261 lysates, was necessary to develop effective immune responses. IT injection of pulsed (pDC), but not unpulsed DCs (uDC), increased significantly the survival, either per se or in combination with SC-pDC (P < .001 vs controls). Mice treated by IT-pDC plus SC pDC survived longer than mice treated by SC-pDC only (P = .03). Injected pDC were detectable in tumor parenchyma, but not in cervical lymph nodes. In gliomas injected with IT-pDC, CD8+ cells were significantly more abundant and Foxp3+ cells were significantly less abundant than in other groups. Using real-time polymerase chain reaction, we also found enhanced expression of IFN-gamma and TNF alpha and decreased expression of transforming growth factor-beta (TGF-beta) and Foxp3 in mice treated with SC-pDC and IT-pDC. In vitro, pDC produced more TNF alpha than uDC: addition of TNF-alpha to the medium decreased the proliferation of glioma cells. Overall, the results suggest that IT-pDC potentiates the anti tumor immune response elicited by SC-pDC by pro-immune modulation of cytokines in the tumor microenvironment, decrease of Treg cells, and direct inhibition of tumor proliferation by TNF-alpha. PMID- 20308316 TI - Chloroquine activates the p53 pathway and induces apoptosis in human glioma cells. AB - Glioblastoma is the most common malignant brain tumor in adults. The currently available treatments offer only a palliative survival advantage and the need for effective treatments remains an urgent priority. Activation of the p53 growth suppression/apoptotic pathway is one of the promising strategies in targeting glioma cells. We show that the quinoline derivative chloroquine activates the p53 pathway and suppresses growth of glioma cells in vitro and in vivo in an orthotopic (U87MG) human glioblastoma mouse model. Induction of apoptosis is one of the mechanisms underlying the effects of chloroquine on suppressing glioma cell growth and viability. siRNA-mediated downregulation of p53 in wild-type but not mutant p53 glioblastoma cells substantially impaired chloroquine-induced apoptosis. In addition to its p53-activating effects, chloroquine may also inhibit glioma cell growth via p53-independent mechanisms. Our results clarify the mechanistic basis underlying the antineoplastic effect of chloroquine and reveal its therapeutic potential as an adjunct to glioma chemotherapy. PMID- 20308317 TI - Intracerebral administration of CpG oligonucleotide for patients with recurrent glioblastoma: a phase II study. AB - Immunostimulating oligodeoxynucleotides containing CpG motifs (CpG-ODN) have shown promising efficacy in cancer models when injected locally. In a phase I clinical trial, intratumoral infusions of CpG-ODN in glioblastoma (GBM) patients were well tolerated at doses up to 20 mg. This phase II trial was designed to study the efficacy of a local treatment by CpG-ODN in patients with recurrent GBMs. Patients with recurrent GBM occurring at least 3 months after radiotherapy, and previously treated with 1 or 2 regimens of chemotherapy received 20 mg of CpG ODN (CpG-28) by convection-enhanced delivery. The primary endpoint was the percentage of patients without tumor progression 6 months after inclusion. Secondary endpoints were tolerance, survival, and radiological response. Thirty four patients were enrolled in two centers between November 2004 and March 2006. Thirty-one patients received CpG-ODN treatment. The progression-free survival (PFS) at 6 months was 19%. One partial response and 3 minor responses were observed. The median overall survival was 28 weeks. Eight patients (24%) were alive 1 year after inclusion and 5 patients (15%) were alive after 2 years. Treatment was usually well tolerated. As reported previously, the most common toxicities were lymphopenia, mild fever, seizures, and transient neurological worsening. Despite a few cases showing a radiological response, CpG-28 showed modest activity on the 6-month PFS in this patient population. The molecular or clinical characteristics of a subgroup of patients that could potentially benefit from such an approach remain to be defined. PMID- 20308318 TI - Meningeal dissemination in primary CNS lymphoma: diagnosis, treatment, and survival in a large monocenter cohort. AB - The frequency of meningeal dissemination (MD) in primary CNS lymphoma (PCNSL), its prognostic impact, and optimal management have not been defined thus far. In 69 of 92 (75%) immunocompetent patients, primarily diagnosed with PCNSL at our institution between January 1994 and February 2007, cerebrospinal fluid was analyzed for MD. MD was found by cytomorphology in 7/63 (11%), by immunophenotyping in 1/32 (3%), and by PCR of the IgH CDR III region in 6/37 (16%). Neuroradiologic examination revealed MD in 3 of 69 patients (4%). Median event-free survival (EFS) of patients with MD diagnosed by any of the methods was 26 months, of those without MD 34.1 months (P = .24); median overall survival (OAS) of these two patients' groups was 45.5 and 42.5 months, respectively (P = .34). Patients with cytomorphologic proof of MD had a median EFS of 15.4 months and OAS of 18.5 months, those without MD 34.3 and 45 months (P = .018 and .017, respectively). We found a low frequency of MD despite the use of putatively sensitive diagnostic methods. No impact on outcome was seen for MD, diagnosed by any of the methods used; however, patients with cytomorphologic proof of MD had a significantly shorter median EFS and OAS. PMID- 20308321 TI - SWR1 complex poises heterochromatin boundaries for antisilencing activity propagation. AB - In eukaryotes, chromosomal processes are usually modulated through chromatin modifying complexes that are dynamically targeted to specific regions of chromatin. In this study, we show that the chromatin-remodeling complex SWR1 (SWR1-C) uses a distinct strategy to regulate heterochromatin spreading. Swr1 binds in a stable manner near heterochromatin to prepare specific chromosomal regions for H2A.Z deposition, which can be triggered by NuA4-mediated acetylation of histone H4. We also demonstrate through experiments with Swc4, a module shared by NuA4 and SWR1-C, that the coupled actions of NuA4 and SWR1-C lead to the efficient incorporation of H2A.Z into chromatin and thereby synergize heterochromatin boundary activity. Our results support a model where SWR1-C resides at the heterochromatin boundary to maintain and amplify antisilencing activity of histone H4 acetylation through incorporating H2A.Z into chromatin. PMID- 20308320 TI - Runx1 directly promotes proliferation of hair follicle stem cells and epithelial tumor formation in mouse skin. AB - Runx1/AML1 is a transcription factor implicated in tissue stem cell regulation and belongs to the small Runx family of cancer genes. In the hair follicle (HF), Runx1 epithelial deletion in morphogenesis impairs normal adult hair homeostasis (cycle) and blocks adult hair follicle stem cells (HFSCs) in quiescence. Here, we show that these effects are overcome later in adulthood. By deleting Runx1 after the end of morphogenesis, we demonstrate its direct role in promoting anagen onset and HFSC proliferation. Runx1 deletion resulted in cyclin-dependent kinase inhibitor Cdkn1a (p21) upregulation. Interfering with Runx1 function in cultured HFSCs impaired their proliferation and normal G(0)/G1 and G(1)/S cell cycle progression. The proliferation defect could be rescued by Runx1 readdition or by p21 deletion. Chemically induced skin tumorigenesis in mice turned on broad Runx1 expression in regions of the skin epithelium, papillomas, and squamous cell carcinomas. In addition, it revealed reduced rates of tumor formation in the absence of Runx1 that were accompanied by decreased epithelial levels of phospho Stat3. Runx1 protein expression was similar in normal human and mouse hair cycles. We propose that Runx1 may act as a skin oncogene by directly promoting proliferation of the epithelial cells. PMID- 20308322 TI - Arginine methylation controls the subcellular localization and functions of the oncoprotein splicing factor SF2/ASF. AB - Alternative splicing and posttranslational modifications (PTMs) are major sources of protein diversity in eukaryotic proteomes. The SR protein SF2/ASF is an oncoprotein that functions in pre-mRNA splicing, with additional roles in other posttranscriptional and translational events. Functional studies of SR protein PTMs have focused exclusively on the reversible phosphorylation of Ser residues in the C-terminal RS domain. We confirmed that human SF2/ASF is methylated at residues R93, R97, and R109, which were identified in a global proteomic analysis of Arg methylation, and further investigated whether these methylated residues regulate the properties of SF2/ASF. We show that the three arginines additively control the subcellular localization of SF2/ASF and that both the positive charge and the methylation state are important. Mutations that block methylation and remove the positive charge result in the cytoplasmic accumulation of SF2/ASF. The consequent decrease in nuclear SF2/ASF levels prevents it from modulating the alternative splicing of target genes, results in higher translation stimulation, and abrogates the enhancement of nonsense-mediated mRNA decay. This study addresses the mechanisms by which Arg methylation and the associated positive charge regulate the activities of SF2/ASF and emphasizes the significance of localization control for an oncoprotein with multiple functions in different cellular compartments. PMID- 20308323 TI - Human AlkB homolog ABH8 Is a tRNA methyltransferase required for wobble uridine modification and DNA damage survival. AB - tRNA nucleosides are extensively modified to ensure their proper function in translation. However, many of the enzymes responsible for tRNA modifications in mammals await identification. Here, we show that human AlkB homolog 8 (ABH8) catalyzes tRNA methylation to generate 5-methylcarboxymethyl uridine (mcm(5)U) at the wobble position of certain tRNAs, a critical anticodon loop modification linked to DNA damage survival. We find that ABH8 interacts specifically with tRNAs containing mcm(5)U and that purified ABH8 complexes methylate RNA in vitro. Significantly, ABH8 depletion in human cells reduces endogenous levels of mcm(5)U in RNA and increases cellular sensitivity to DNA-damaging agents. Moreover, DNA damaging agents induce ABH8 expression in an ATM-dependent manner. These results expand the role of mammalian AlkB proteins beyond that of direct DNA repair and support a regulatory mechanism in the DNA damage response pathway involving modulation of tRNA modification. PMID- 20308324 TI - Positive regulation of interferon regulatory factor 3 activation by Herc5 via ISG15 modification. AB - Virus infection induces host antiviral responses, including induction of type I interferons. Transcription factor interferon regulatory factor 3 (IRF3) plays a pivotal role and is tightly regulated in this process. Here, we identify HERC5 (HECT domain and RLD 5) as a specific binding protein of IRF3 by immunoprecipitation. Ectopic expression or knockdown of HERC5 could, respectively, enhance or impair IRF3-mediated gene expression. Mechanistically, HERC5 catalyzes the conjugation of ubiquitin-like protein ISG15 onto IRF3 (Lys193, -360, and -366), thus attenuating the interaction between Pin1 and IRF3, resulting in sustained IRF3 activation. In contrast to results for wild-type IRF3, the mutant IRF3(K193,360,366R) interacts tightly with Pin1, is highly polyubiquitinated, and becomes less stable upon Sendai virus (SeV) infection. Consistently, host antiviral responses are obviously boosted or crippled in the presence or absence of HERC5, respectively. Collectively, this study characterizes HERC5 as a positive regulator of innate antiviral responses. It sustains IRF3 activation via a novel posttranslational modification, ISGylation. PMID- 20308325 TI - Ephrin-B1 reverse signaling controls a posttranscriptional feedback mechanism via miR-124. AB - Eph receptors and ephrins exhibit complex and highly dynamic expression patterns during embryonic development. In addition, changes in their expression levels are often associated with pathological situations in adults. Yet, little is known about the mechanisms regulating their expression. Here we report that the expression of ephrin-B1 is controlled by a feedback loop involving posttranscriptional regulatory mechanisms. We observed that the EfnB1 3' untranslated region (3'-UTR) confers instability to mRNA transcripts, and we identified miR-124 as a posttranscriptional repressor of EfnB1 expression. Furthermore, we showed that miR-124 is itself regulated by ephrin-B1 reverse signaling, thus revealing the existence of a mutually repressive interaction between ephrin-B1 and this microRNA (miRNA). Lastly, we demonstrated the relevance of this mutual inhibition for neuronal differentiation. Our results suggest that miRNAs could be important effectors of Eph/ephrin signaling to refine domains of expression and to regulate function. PMID- 20308326 TI - Mechanism of Mediator recruitment by tandem Gcn4 activation domains and three Gal11 activator-binding domains. AB - Targets of the tandem Gcn4 acidic activation domains in transcription preinitiation complexes were identified by site-specific cross-linking. The individual Gcn4 activation domains cross-link to three common targets, Gal11/Med15, Taf12, and Tra1, which are subunits of four conserved coactivator complexes, Mediator, SAGA, TFIID, and NuA4. The Gcn4 N-terminal activation domain also cross-links to the Mediator subunit Sin4/Med16. The contribution of the two Gcn4 activation domains to transcription was gene specific and varied from synergistic to less than additive. Gcn4-dependent genes had a requirement for Gal11 ranging from 10-fold dependence to complete Gal11 independence, while the Gcn4-Taf12 interaction did not significantly contribute to the expression of any gene studied. Complementary methods identified three conserved Gal11 activator binding domains that bind each Gcn4 activation domain with micromolar affinity. These Gal11 activator-binding domains contribute additively to transcription activation and Mediator recruitment at Gcn4- and Gal11-dependent genes. Although we found that the conserved Gal11 KIX domain contributes to Gal11 function, we found no evidence of specific Gcn4-KIX interaction and conclude that the Gal11 KIX domain does not function by specific interaction with Gcn4. Our combined results show gene-specific coactivator requirements, a surprising redundancy in activator-target interactions, and an activator-coactivator interaction mediated by multiple low-affinity protein-protein interactions. PMID- 20308327 TI - A glycine-rich domain of hnRNP H/F promotes nucleocytoplasmic shuttling and nuclear import through an interaction with transportin 1. AB - Heterogeneous nuclear ribonucleoprotein (hnRNP) H and F are members of a closely related subfamily of hnRNP proteins that are implicated in many aspects of RNA processing. hnRNP H and F are alternative splicing factors for numerous U2- and U12-dependent introns. The proteins have three RNA binding domains and two glycine-rich domains and localize to both the nucleus and cytoplasm, but little is known about which domains govern subcellular localization or splicing activity. We show here that the central glycine-tyrosine-arginine-rich (GYR) domain is responsible for nuclear localization, and a nonclassical nuclear localization signal (NLS) was mapped to a short, highly conserved sequence whose activity was compromised by point mutations. Glutathione S-transferase (GST) pulldown assays demonstrated that the hnRNP H NLS interacts with the import receptor transportin 1. Finally, we show that hnRNP H/F are transcription dependent shuttling proteins. Collectively, the results suggest that hnRNP H and F are GYR domain-dependent shuttling proteins whose posttranslational modifications may alter nuclear localization and hence function. PMID- 20308328 TI - Functional effects of PTPN11 (SHP2) mutations causing LEOPARD syndrome on epidermal growth factor-induced phosphoinositide 3-kinase/AKT/glycogen synthase kinase 3beta signaling. AB - LEOPARD syndrome (LS), a disorder with multiple developmental abnormalities, is mainly due to mutations that impair the activity of the tyrosine phosphatase SHP2 (PTPN11). How these alterations cause the disease remains unknown. We report here that fibroblasts isolated from LS patients displayed stronger epidermal growth factor (EGF)-induced phosphorylation of both AKT and glycogen synthase kinase 3beta (GSK-3beta) than fibroblasts from control patients. Similar results were obtained in HEK293 cells expressing LS mutants of SHP2. We found that the GAB1/phosphoinositide 3-kinase (PI3K) complex was more abundant in fibroblasts from LS than control subjects and that both AKT and GSK-3beta hyperphosphorylation were prevented by reducing GAB1 expression or by overexpressing a GAB1 mutant unable to bind to PI3K. Consistently, purified recombinant LS mutants failed to dephosphorylate GAB1 PI3K-binding sites. These mutants induced PI3K-dependent increase in cell size in a model of chicken embryo cardiac explants and in transcriptional activity of the atrial natriuretic factor (ANF) gene in neonate rat cardiomyocytes. In conclusion, SHP2 mutations causing LS facilitate EGF-induced PI3K/AKT/GSK-3beta stimulation through impaired GAB1 dephosphorylation, resulting in deregulation of a novel signaling pathway that could be involved in LS pathology. PMID- 20308329 TI - Effects of the cognition-enhancing agent ABT-239 on fetal ethanol-induced deficits in dentate gyrus synaptic plasticity. AB - Prenatal ethanol exposure causes deficits in hippocampal synaptic plasticity and learning. At present, there are no clinically effective pharmacotherapeutic interventions for these deficits. In this study, we examined whether the cognition-enhancing agent 4-(2-{2-[(2R)-2-methylpyrrolidinyl]ethyl}-benzofuran-5 yl) benzonitrile (ABT-239), a histamine H(3) receptor antagonist, could ameliorate fetal ethanol-induced long-term potentiation (LTP) deficits. Long Evans rat dams consumed a mean of 2.82 g/kg ethanol during a 4-h period each day. This voluntary drinking pattern produced a mean peak serum ethanol level of 84 mg/dl. Maternal weight gain, offspring litter size, and birth weights were not different between ethanol-consuming and control groups. A stimulating electrode was implanted in the entorhinal cortical perforant path, and a recording electrode was implanted in the dorsal dentate gyrus of urethane-anesthetized adult male offspring. Baseline input/output responses were not affected either by prenatal ethanol exposure or by 1 mg/kg ABT-239 administered 2 h before data collection. No differences were observed between prenatal treatment groups when a 10-tetanus train protocol was used to elicit LTP. However, LTP elicited by 3 tetanizing trains was markedly impaired by prenatal ethanol exposure compared with control. This fetal ethanol-induced LTP deficit was reversed by ABT-239. In contrast, ABT-239 did not enhance LTP in control offspring using the 3-tetanus train protocol. These results suggest that histamine H(3) receptor antagonists may have utility for treating fetal ethanol-associated synaptic plasticity and learning deficits. Furthermore, the differential effect of ABT-239 in fetal alcohol offspring compared with controls raises questions about the impact of fetal ethanol exposure on histaminergic modulation of excitatory neurotransmission in affected offspring. PMID- 20308330 TI - Glucocorticoid-dependent expression of O(6)-methylguanine-DNA methyltransferase gene modulates dacarbazine-induced hepatotoxicity in mice. AB - O(6)-methylguanine-DNA methyltransferase (MGMT) plays a crucial role in the defense against the alkylating agent-induced cytotoxic lesion O(6)-alkylguanine in DNA. Although a significant circadian variation in MGMT activity has been found in the liver of mice, the exact mechanism of the variation remains poorly understood. In this study, we present evidence that glucocorticoids were required for the 24-h oscillation of MGMT expression in mouse liver. The exposure of mouse hepatic cells (Hepa1-6) to dexamethasone (DEX) significantly increased the mRNA levels of MGMT in a dose-dependent manner. The DEX-induced increase in MGMT expression was reversed by concomitant treatment with RU486 [11beta-[p (dimethylamino) phenyl]-17beta-hydroxy-17-(1-propynyl)estra-4,9-dien-3-one], a glucocorticoid receptor antagonist. The mRNA levels of MGMT and its enzymatic activity in the liver of mice showed significant 24-h oscillations, which were not observed in adrenalectomized mice. A single administration of DEX to adrenalectomized mice significantly increased the mRNA levels of MGMT in the liver. These findings suggest that the 24-h oscillation in the hepatic expression of MGMT is caused by the endogenous rhythm of glucocorticoid secretion. Dacarbazine (DTIC), a potent O(6)-guanine-alkylating agent, causes serious hepatotoxicity accompanied by hepatocellular necrosis and hepatic vein thrombosis. DTIC-induced hepatotoxicity in mice was attenuated by administering the drug at the time of day when MGMT expression was abundant. The present findings suggest that glucocorticoid-regulated oscillation in the hepatic MGMT expression is the underlying cause of dosing time-dependent changes in DTIC induced hepatotoxicity. PMID- 20308331 TI - Protection against acute kidney injury via A(1) adenosine receptor-mediated Akt activation reduces liver injury after liver ischemia and reperfusion in mice. AB - Hepatic ischemia reperfusion (IR) injury causes acute kidney injury (AKI). However, the contribution of AKI to the pathogenesis of liver IR injury is unclear. Furthermore, controversy still exists regarding the role of A(1) adenosine receptors (A(1)ARs) in AKI. In this study, we determined whether exogenous and endogenous A(1)AR activation protects against AKI with subsequent liver protection after hepatic IR in mice. We found that after hepatic IR A(1) knockout (KO) mice and A(1)AR antagonist-treated A(1) wild-type (WT) mice developed worse AKI and liver injury compared with vehicle-treated A(1)WT mice. Moreover, a selective A(1)AR agonist protected against hepatic IR-induced AKI and liver injury in A(1)WT mice. Renal A(1)AR-mediated kidney protection plays a crucial role in protecting the liver after IR because: 1) selective unilateral renal lentiviral overexpression of human A(1)ARs [enhanced green fluorescent protein (EGFP)-huA(1)AR] in A(1)KO mice protected against both kidney and liver injury sustained after liver IR, 2) removal of the EGFP-huA(1)AR lentivirus injected kidney from A(1)KO mice abolished both renal and hepatic protection after liver IR, and 3) bilateral nephrectomy before hepatic ischemia abolished the protective effects of A(1)AR activation in A(1)WT mice. Finally, inhibition of Akt, but not extracellular signal-regulated kinase mitogen-activated protein kinase, prevented the kidney and liver protection afforded by A(1)AR agonist treatment. Taken together, we show that endogenous and exogenous activation of renal A(1)ARs protect against liver and kidney injury after liver IR in vivo via pathways involving Akt activation. PMID- 20308335 TI - The impact of a short-term intervention using the WHO guidelines for the management of severe malnutrition at a rural facility in Angola. AB - OBJECTIVE: To measure the impact of practice review and in-service supervision based on WHO guidelines on outcomes of severely malnourished children in a rural facility with minimal resources staffed only by nurses. DESIGN: Intervention (January to August 2006) with historical comparison of outcomes (January to August 2005). SETTING: Therapeutic feeding centre in rural Angola. PATIENTS: All children admitted to the feeding centre during the study period. INTERVENTION: Medecins Du Monde implemented an intervention that consisted of weekly physician supervision of staff activities and establishment of a study group composed of nurses in the centre. MAIN OUTCOME MEASURES: Routine practices in the centre and measured indicators for outcomes of admitted children, which were compared to indicators before the intervention. RESULTS: During the intervention the authors observed improved delivery of important tasks such as frequent feeding and avoidance of intravenous rehydration. Among the 379 children admitted during the intervention, compared to the 358 children admitted previously, successful treatment increased from 73.2% to 82.6% (RR 1.13; 95% CI 1.04 to 1.22) and fatalities decreased from 15.6% to 8.7% (RR 0.56; 95% CI 0.37 to 0.83). CONCLUSION: This short-term intervention with in-service supervision based on the WHO guidelines in a setting of limited resources apparently contributed to a reduction in fatality rates. These findings support the view that such guidelines can be effectively implemented in under-resourced facilities in Angola and similar settings if they are introduced using an interactive approach and if in service supervision continues to be provided. PMID- 20308337 TI - Extreme leucocytosis and the risk of serious bacterial infections in febrile children. AB - OBJECTIVE: To determine the clinical significance of extreme leucocytosis (white blood cell (WBC) count >25,000/mm(3)) as a predictor of serious bacterial infection (SBI) in children. PATIENTS AND METHODS: A retrospective case-control study was conducted in a paediatric emergency department in Israel. The study evaluated children aged 3-36 months admitted to the emergency department with fever (>38 degrees C) who had a complete blood count (CBC). Children with extreme leucocytosis were identified through the laboratory database. Further, for each case patient two consecutive febrile patients with WBC counts of 15,000 24,999/mm(3) (moderate leucocytosis) served as controls (a case-control ratio of 1:2). RESULTS: During the study, 146 patients with extreme leucocytosis were identified and compared with 292 patients with moderate leucocytosis. SBI was found in 57 (39%) patients with extreme leucocytosis compared with 45 (15.4%) control patients (p<0.001). The most commonly found SBI was segmental or lobar pneumonia, which was diagnosed in 41 (28%) patients in the case group compared with 27 (9.2%) patients in the control group (p<0.001, OR 3.83, 95% CI 2.25 to 6.52). Children with extreme leucocytosis were more often treated with antibiotics (52.7% vs 27.7%, p<0.001) and admitted to hospital (98.6% vs 50.68%, p<0.001). CONCLUSIONS: In febrile children aged 3-36 months, the presence of extreme leucocytosis is associated with a 39% risk of having SBIs. The increased risk for SBI is mainly due to a higher risk for pneumonia. PMID- 20308338 TI - Images in paediatrics: Multiple button battery ingestion. PMID- 20308339 TI - Breast feeding and drug therapy in neglected diseases. PMID- 20308340 TI - Question 1. Is delayed clamping of the umbilical cord in moderately preterm babies beneficial? PMID- 20308341 TI - Towards evidence based medicine for paediatricians. PMID- 20308342 TI - Question 2. Which medications effectively reduce pubertal gynaecomastia? PMID- 20308343 TI - Question 3. Do Portacaths or Hickman lines have a higher risk of catheter-related bloodstream infections in children with leukaemia? PMID- 20308344 TI - Emotional, self-conceptual, and relational characteristics of bullies and the bullied. AB - AIMS: To clarify distributions of emotional and somatic symptoms among different groups involved in bullying behaviour during early adolescence; to explore differences in social integration and self-perceptions; to explore how different cut-off limits for bullying behaviour may affect the impact of these measures; and to interpret our findings in the light of theories of identity that may suggest directions for interventions against bullying in schools. METHODS: A cross-sectional study, based on self-completion questionnaire, of 1237 pupils aged 11-15 years in autumn 2000 in Alesund, Norway. RESULTS: Bullies and their victims reported similar and greater emotional impairments and psychosomatic complaints, lack of self-confidence, and pessimism than students not involved in bullying. With increasing involvement, bullies differed from non-involved students only in regard to depressive complaints and pessimism. The bullied group reported more depressive, somatic and anxiety complaints, and self-reproach with increasing victimisation. Both bullies and the bullied reported problems relating to school, parents, and teachers. Bullies enjoyed friendships to the same degree or better than their peers not involved in bullying, whereas the bullied group reported impaired peer relations and increasing problems with more serious involvement. Bullies, the bullied, and bully-victims reported diminishing peer support in their class with increasing involvement. CONCLUSIONS: Both the bullied and bullies share relational, emotional, and self-conceptual problems, but they also differ in whether they succeed in social arenas and to what extent they are affected by different emotional and self-conceptual problems. They are, however, fellow sufferers in many aspects. PMID- 20308345 TI - Advancing towards a tissue-engineered tympanic membrane: silk fibroin as a substratum for growing human eardrum keratinocytes. AB - Human tympanic membrane cells (hTMCs), harvested from tympanic membrane (TM) explants, were grown in culture and then seeded on membranes prepared from silkworm (Bombyx mori) silk fibroin (BMSF) and on tissue-culture plastic membranes (PET). Fibroin was isolated from silk cast into membranes with a thickness of 10-15 microm. The hTMCs were cultured on both materials for 15 days in a serum-containing culture medium. The cells grown on both substrata were subjected to nuclear staining (DAPI) and counted. Further, the cultures were immunostained for a number of protein markers related to the epithelial/keratinocyte phenotype and cell adhesion complexes. The BMSF membranes supported levels of hTMC growth higher than that observed on the PET membranes. The immunofluorochemical analysis indicated unequivocally that BMSF is a more suitable substratum than PET with respect to the growth patterns, proliferation, and cell-cell contact and adhesion. BMSF appear as a promising substratum in the tissue-engineered constructs for the replacement of TM in case of nonhealing perforations. PMID- 20308346 TI - Moving beyond the notion of 'self' care. PMID- 20308347 TI - Emerging models for mobilizing family support for chronic disease management: a structured review. AB - OBJECTIVES: We identify recent models for programmes aiming to increase effective family support for chronic illness management and self-care among adult patients without significant physical or cognitive disabilities. We then summarize evidence regarding the efficacy for each model identified. METHODS: Structured review of studies published in medical and psychology databases from 1990 to the present, reference review, general Web searches and conversations with family intervention experts. Review was limited to studies on conditions that require ongoing self-management, such as diabetes, chronic heart disease and rheumatologic disease. RESULTS: Programmes with three separate foci were identified: (1) Programmes that guide family members in setting goals for supporting patient self-care behaviours have led to improved implementation of family support roles, but have mixed success improving patient outcomes. (2) Programmes that train family in supportive communication techniques, such as prompting patient coping techniques or use of autonomy supportive statements, have successfully improved patient symptom management and health behaviours. (3) Programmes that give families tools and infrastructure to assist in monitoring clinical symptoms and medications are being conducted, with no evidence to date on their impact on patient outcomes. DISCUSSION: The next generation of programmes to improve family support for chronic disease management incorporate a variety of strategies. Future research can define optimal clinical situations for family support programmes, the most effective combinations of support strategies, and how best to integrate family support programmes into comprehensive models of chronic disease care. PMID- 20308348 TI - Family influences on self-management among functionally independent adults with diabetes or heart failure: do family members hinder as much as they help? AB - OBJECTIVES: Among functionally independent patients with diabetes or heart failure, we examined family member support and family-related barriers to self care. We then identified patient characteristics associated with family support and family barriers and how each was associated with self-management adherence. METHODS: Cross-sectional survey of 439 patients with diabetes or heart failure (74% response rate). RESULTS: 75% of respondents reported supportive family involvement in self-care; however, 25% reported frequent family-related barriers to self-care. Women reported family support less often (64% v. 77%) and family barriers to self-care more often (30% v. 21%) than men. 78% of respondents reported involved family members nagged or criticized them about illness care. In multivariate models, low health literacy, partnered status and higher family function were associated with higher family support levels, while female gender, older age, higher education, and more depression symptoms were associated with family barriers to self-care. Family barriers were associated with lower disease care self-efficacy (p<0.01), and both barriers and family support were associated with patients' self-management adherence (both p<0.05). DISCUSSION: Family members are highly involved in the self-care of these higher functioning patients. Interventions should help patients with chronic illness overcome family barriers to self-care and help families use positive and effective support techniques. PMID- 20308349 TI - The case for involving adult children outside of the household in the self management support of older adults with chronic illnesses. AB - OBJECTIVES: This study sought to (1) identify barriers to spousal support for chronic illness self-care among community-dwelling older adults; and (2) describe the potential availability of self-care support from adult children living outside of the household. METHODS: Nationally representative US sample of chronically ill adults aged 51+ were interviewed as part of the Health and Retirement Study (N = 14,862). Both participants and their spouses (when available) reported information about their health and functioning. Participants also reported information about their contact with adult children and the quality of those relationships. RESULTS: More than one-third (38%) of chronically ill older adults in the US are unmarried; and when spouses are available, the majority of them have multiple chronic diseases and functional limitations. However, the vast majority of chronically ill older adults (93%, representing roughly 60 million Americans) have adult children, with half having children living over 10 miles away. Most respondents with children (78%) reported at least weekly telephone contact and that these relationships were positive. Roughly 19 million older chronically ill Americans have adult children living at a distance but none nearby; these children are in frequent telephone contact and respondents (including those with multiple chronic diseases) report that the relationships are positive. DISCUSSION: As the gap between available health services for disease management and the need among community-dwelling patients continues to grow, adult children-including those living at a distance-represent an important resource for improving self-care support for people with chronic diseases. PMID- 20308350 TI - Patient-caregiver concordance in symptom assessment and improvement in outcomes for patients undergoing cancer chemotherapy. AB - OBJECTIVE: To measure the agreement between cancer patients' and family caregivers' perceptions of the patients' symptom severity, and the association between changes in caregiver accuracy and changes in outcomes. METHODS: Secondary analysis of baseline and 10-week follow-up data from 142 cancer patient/caregiver dyads. Patient/caregiver agreement about symptom burden was measured for the 8 most prevalent symptoms and overall. Bivariate analyses examined the patient and caregiver characteristics associated with caregivers who were overestimators, underestimators or accurate at baseline. We tested the relationship between change in caregiver accuracy and both caregiver behaviour (e.g. use of information, hours spent caregiving) and patient outcomes (e.g. total symptom severity and frequency). RESULTS: At baseline, caregivers overestimated the severity of 17 out of 18 symptoms; 50% predicted mean symptom severity accurately. Accuracy worsened over time for 51%, stayed the same for 36%, and improved for 13%. While not statistically significant, caregivers whose accuracy improved over time had patients who reported greater declines in: symptom severity, number of symptoms, symptom interference, total symptom frequency and depression. In addition, these caregivers experienced greater reductions in their use of information and hours helping the patient. DISCUSSION: Caregivers typically over-estimate cancer patients' symptom burden and accuracy does not improve over time. Improving caregiver accuracy may boost the positive effects of cognitive behavioural interventions designed to improve cancer patients' quality of life. PMID- 20308351 TI - Informal and formal care infrastructure and perceived need for caregiver training for frail US veterans referred to home and community-based services. AB - OBJECTIVES: To describe the informal care network of US veterans referred to home and community-based services (Homemaker Home Health services, H/HHA, or Home Based Primary Care, HBPC) at the Durham Veterans Affairs Medical Center (VAMC), including: quantity and types of tasks provided and desired content for caregiver training programs. METHODS: All primary care patients referred to H/HHA or HBPC during the preceding 3 months were sent questionnaires in May 2007. Additionally, caregivers were sent questionnaires if a patient gave permission. Descriptive statistics and chi-squared tests were performed. RESULTS: On average, patients received 5.6 hours of VA care and 47 hours of informal care per week. 26% of patients (38% of patients with caregiver proxy respondents) and 59% of caregivers indicated the caregiver would be interested in participating in a training program by phone or on-site. Significant barriers to participation existed. The most common barriers were: transportation; no time due to caregiving or work demands; caregiver's own health limitations; and no need. CONCLUSIONS: Caregiver training needs to be tailored to overcome barriers to participate. Overcoming these barriers may be possible through in-home phone or internet training outside traditional business hours, and by tailoring training to accommodate limiting health problems among caregivers. PMID- 20308352 TI - Psychological health in older adult spousal caregivers of older adults. AB - OBJECTIVES: The need for informal caregiving has been rapidly increasing across several countries. Spouses comprise a sizeable segment of informal caregivers and typically represent an older cohort with special health concerns. The objective of this review was to examine psychological health outcomes in older adult spouses caring for older adults. METHODS: Literature review/synthesis (1999 2009). RESULTS: Compared to demographically matched married non-caregiving controls, older adult spousal caregivers experienced more cognitive functioning difficulties, strain, distress, stress, loneliness, depression, anxiety and poorer mental health. Caregivers of spouses with cognitive impairments, quite often wives, were especially affected by poor psychological health, as were caregivers who were new to the caregiving role and those who rated caregiving as stressful. Psychological health improved when the caregiving role ceased. DISCUSSION: Several poor psychological outcomes were found in older adults caring for their spouses; the magnitude of which varied and were more pronounced under certain circumstances. To preserve caregiver health, maintain recipient health and care quality and avoid exceeding system of care capacity, efforts are needed to provide support to older adult spousal caregivers and recipients. Couples may need to be assessed as a unit, taking gender and cultural considerations into account, and additional resources may be required. PMID- 20308353 TI - Endurance of multiplication fact fluency for students with attention deficit hyperactivity disorder. AB - This study examines the relationship between a critical learning outcome of behavioral fluency and endurance, by comparing the effects of two practice procedures on multiplication facts two through nine. The first procedure, called whole time practice trial, consisted of an uninterrupted 1 minute practice time. The second procedure, endurance building practice trials, had three 20 second practice trials. A total of 3 students with attention deficit hyperactivity disorder participated. Results indicated that multiplication facts with the endurance building practice trials produced more efficient learning when compared to the whole time practice trial procedure for all 3 participants. Additionally, results show that even with the amount of practice time being equal, 1 minute in both conditions, on average participants practiced 30% more problems with the endurance building practice trials procedure than they did with the whole time practice trial procedure. PMID- 20308354 TI - The impact of acceptance-based versus avoidance-based protocols on discomfort. AB - This study aimed to isolate the conditions under which aversive stimulation is experienced as more or less discomforting/unpleasant. Discomfort was induced by playing loud noises through headphones while participants performed computer tasks. We employed 4 main conditions. Condition 1: the acceptance-based protocol (ACT), intended to integrate discomfort in a valued direction, was implemented before the Inclusion Task (task performance could continue despite the presence of the noise). Subsequently, the experiential avoidance-based protocol (EA), intended to promote a relation of opposition between discomfort and valued actions, was implemented before the Opposition Task (task performance was suspended until the participants eliminated the sounds). Condition 2: this order was reversed. Conditions 3 and 4: the tasks were presented without any protocol. The ACT protocol produced the lowest level of discomfort, particularly when it was implemented before participants had experimental experience in trying to control discomfort. Two postcontrol conditions confirmed this result. Implications for prevention and treatment of psychological suffering are discussed. PMID- 20308355 TI - Experiential avoidance and problem behavior: a mediational analysis. AB - Despite their formal dissimilarity, problem behaviors (e.g., substance misuse, binge eating, self-harm) may share a common function. According to Acceptance and Commitment Therapy (ACT), this shared function is Experiential Avoidance, the process of avoiding, escaping or otherwise altering unwanted private events (e.g., thoughts, feelings, memories) and the contexts that elicit them. Structural Equation Modeling was used cross-sectionally with data from a clinical opportunity sample ( N = 290) to test (a) whether problem behavior covariance was associated with experiential avoidance, and (b) whether experiential avoidance mediated the relationships between historical and dispositional risk factors (childhood trauma and negative affect intensity, respectively) and the tendency to engage in problem behaviors. Analysis showed that experiential avoidance contributed to the covariation of problem behaviors, and that it fully mediated the relationships between both risk factors and problem behavior. Thus, experiential avoidance may be a key process to target in the management of individuals with behavior problems. PMID- 20308356 TI - Vasovagal syncope and blood donor return: examination of the role of experience and affective expectancies. AB - Vasovagal sensations (e.g., dizziness, nausea, and fainting) are one of the main reasons people find blood donation unpleasant. A better understanding of predictors of vasovagal sensations during blood donation could inform interventions designed to increase donor return rates. The present investigation examined the extent to which experience with blood donation and vasovagal sensations during blood donation uniquely predict the likelihood of donor return, even when controlling for affective expectancies. Participants presenting at community blood drives indicated how many times they have given blood and provided ratings of expected anxiety, pain, disgust, as well as fear of fainting before giving blood. After donating, participants completed a measure of vasovagal sensations experienced during blood donation. They also rated the pleasantness of the experience and willingness to donate blood in the future. The findings showed that experience with blood donation and vasovagal sensations during blood donation uniquely predicted willingness to donate blood in the future even when controlling for age and negative affective expectancies about giving blood. This finding suggests that vasovagal sensations and experience with blood donation have unique (and perhaps additive) effects on willingness to donate blood in the future, suggesting that behavior modification interventions that directly target these variables could potentially increase donor retention. PMID- 20308357 TI - Acceptance and commitment therapy versus cognitive therapy for the treatment of comorbid eating pathology. AB - Previous research has indicated that although eating pathology is prevalent in college populations, both CBT and non-CBT-based therapies achieve only limited effectiveness. The current study examined several questions related to the treatment of eating pathology within the context of a larger randomized controlled trial that compared standard CBT (i.e., Beck's cognitive therapy; CT) with acceptance and commitment therapy (ACT; Hayes, 2004).The results indicated that the two treatments were differentially effective at reducing eating pathology. Specifically, CT produced modest decreases in eating pathology whereas ACT produced large decreases. In addition, a weaker suggestion emerged that ACT was more effective than CT at increasing clinician-rated global functioning among those with eating pathology. These findings suggest that ACT is a useful treatment for disordered eating and potentially, for eating disorders per se. PMID- 20308359 TI - Increased serum level of early prostate cancer antigen is associated with subsequent cancer risk in men with high-grade prostatic intraepithelial neoplasia. AB - Early prostate cancer antigen (EPCA) has been recently suggested as a novel biomarker in malignant and premalignant lesions of the prostate. This study was to examine serum expression of EPCA and to further clarify the relationship between initial serum EPCA levels and the presence of subsequent cancer in the individuals with isolated high-grade prostatic intraepithelial neoplasia (HGPIN). An indirect ELISA was used for initial serum EPCA measurement in 112 men with isolated HGPIN, who were enrolled and completed a follow-up of >or=5 years. All patients had a detectable concentration of EPCA in the initial serum, with a mean of 0.64+/-0.13 absorbance at 450 nm. Thirty-three patients had an initial serum EPCA level of >or=1.10, in which 31 cases were subsequently identified as having prostate cancer on follow-up. However, in the remaining 79 cases, serum EPCA levels were all <1.10, and none was diagnosed with cancer later. Statistical analysis showed a significantly higher serum ECPA level in isolated HGPIN patients with subsequent cancer than those without cancer (P<0.001). The area under the receiver operating characteristic curves showed that serum EPCA level had better predictive accuracy of cancer onset on follow-up than prostate specific antigen velocity and abnormal digital rectal examination findings. Furthermore, univariate and multivariate Cox regression analyses demonstrated the predictive performance independently by initial serum EPCA>or=1.10 absorbance (relative risk, 3.32; 95% confidence intervals, 2.62-5.03, P<0.001). These preliminary findings first show the potential of serum EPCA to serve as a significant predictor for subsequent cancer in isolated HGPIN. PMID- 20308360 TI - Human heterochromatin protein 1 isoform HP1beta enhances androgen receptor activity and is implicated in prostate cancer growth. AB - There are currently few successful therapies for castration-resistant prostate cancer (CRPC). CRPC is thought to result from augmented activation of the androgen/androgen receptor (AR) signaling pathway, which could be enhanced by AR cofactors. In this study, heterochromatin protein 1beta (HP1beta), but not HP1alpha or HP1gamma was found to be an AR cofactor. HP1beta interacted with the AR, and enhanced the DNA-binding ability of AR to androgen-responsive element in the prostate-specific antigen enhancer and promoter regions, and to increase the transcription of AR target genes. In prostate cancer (PCa) tissues, HP1beta expressions correlated with Gleason score and tri-methylation levels of histone H3 lysine 9. Silencing of HP1beta suppressed the growth of AR-expressing PCa cells by inducing cell-cycle arrest at the G(1) phase, similar to inhibition of androgen/AR signaling. Furthermore, HP1beta was overexpressed in castration resistant LNCaP derivative CxR cells, and HP1beta knockdown also suppressed the cell growth in CxR cells. These findings indicate that HP1beta is involved in the proliferation of AR-expressing PCa cells and progression to CRPC as an AR coactivator. Modulation of HP1beta expression or function might be a useful strategy for developing novel therapeutics for PCa, even in CRPC. PMID- 20308361 TI - Antagonism of the complement component C4 by flavivirus nonstructural protein NS1. AB - The complement system plays an essential protective role in the initial defense against many microorganisms. Flavivirus NS1 is a secreted nonstructural glycoprotein that accumulates in blood, is displayed on the surface of infected cells, and has been hypothesized to have immune evasion functions. Herein, we demonstrate that dengue virus (DENV), West Nile virus (WNV), and yellow fever virus (YFV) NS1 attenuate classical and lectin pathway activation by directly interacting with C4. Binding of NS1 to C4 reduced C4b deposition and C3 convertase (C4b2a) activity. Although NS1 bound C4b, it lacked intrinsic cofactor activity to degrade C4b, and did not block C3 convertase formation or accelerate decay of the C3 and C5 convertases. Instead, NS1 enhanced C4 cleavage by recruiting and activating the complement-specific protease C1s. By binding C1s and C4 in a complex, NS1 promotes efficient degradation of C4 to C4b. Through this mechanism, NS1 protects DENV from complement-dependent neutralization in solution. These studies define a novel immune evasion mechanism for restricting complement control of microbial infection. PMID- 20308362 TI - Lymph node fibroblastic reticular cells directly present peripheral tissue antigen under steady-state and inflammatory conditions. AB - Lymph node stromal cells (LNSCs) can induce potent, antigen-specific T cell tolerance under steady-state conditions. Although expression of various peripheral tissue-restricted antigens (PTAs) and presentation to naive CD8+ T cells has been demonstrated, the stromal subsets responsible have not been identified. We report that fibroblastic reticular cells (FRCs), which reside in the T cell zone of the LN, ectopically express and directly present a model PTA to naive T cells, inducing their proliferation. However, we found that no single LNSC subset was responsible for PTA expression; rather, each subset had its own characteristic antigen display. Studies to date have concentrated on PTA presentation under steady-state conditions; however, because LNs are frequently inflammatory sites, we assessed whether inflammation altered stromal cell-T cell interactions. Strikingly, FRCs showed reduced stimulation of T cells after Toll like receptor 3 ligation. We also characterize an LNSC subset expressing the highest levels of autoimmune regulator, which responds potently to bystander inflammation by up-regulating PTA expression. Collectively, these data show that diverse stromal cell types have evolved to constitutively express PTAs, and that exposure to viral products alters the interaction between T cells and LNSCs. PMID- 20308363 TI - Cerebral cavernous malformations proteins inhibit Rho kinase to stabilize vascular integrity. AB - Endothelial cell-cell junctions regulate vascular permeability, vasculogenesis, and angiogenesis. Familial cerebral cavernous malformations (CCMs) in humans result from mutations of CCM2 (malcavernin, OSM, MGC4607), PDCD10 (CCM3), or KRIT1 (CCM1), a Rap1 effector which stabilizes endothelial cell-cell junctions. Homozygous loss of KRIT1 or CCM2 produces lethal vascular phenotypes in mice and zebrafish. We report that the physical interaction of KRIT1 and CCM2 proteins is required for endothelial cell-cell junctional localization, and lack of either protein destabilizes barrier function by sustaining activity of RhoA and its effector Rho kinase (ROCK). Protein haploinsufficient Krit1(+/-) or Ccm2(+/-) mouse endothelial cells manifested increased monolayer permeability in vitro, and both Krit1(+/-) and Ccm2(+/-) mice exhibited increased vascular leak in vivo, reversible by fasudil, a ROCK inhibitor. Furthermore, we show that ROCK hyperactivity occurs in sporadic and familial human CCM endothelium as judged by increased phosphorylation of myosin light chain. These data establish that KRIT1 CCM2 interaction regulates vascular barrier function by suppressing Rho/ROCK signaling and that this pathway is dysregulated in human CCM endothelium, and they suggest that fasudil could ameliorate both CCM disease and vascular leak. PMID- 20308364 TI - A novel Rac-dependent checkpoint in B cell development controls entry into the splenic white pulp and cell survival. AB - Rac1 and Rac2 GTPases transduce signals from multiple receptors leading to cell migration, adhesion, proliferation, and survival. In the absence of Rac1 and Rac2, B cell development is arrested at an IgD- transitional B cell stage that we term transitional type 0 (T0). We show that T0 cells cannot enter the white pulp of the spleen until they mature into the T1 and T2 stages, and that this entry into the white pulp requires integrin and chemokine receptor signaling and is required for cell survival. In the absence of Rac1 and Rac2, transitional B cells are unable to migrate in response to chemokines and cannot enter the splenic white pulp. We propose that loss of Rac1 and Rac2 causes arrest at the T0 stage at least in part because transitional B cells need to migrate into the white pulp to receive survival signals. Finally, we show that in the absence of Syk, a kinase that transduces B cell antigen receptor signals required for positive selection, development is arrested at the same T0 stage, with transitional B cells excluded from the white pulp. Thus, these studies identify a novel developmental checkpoint that coincides with B cell positive selection. PMID- 20308365 TI - Lymph node-resident lymphatic endothelial cells mediate peripheral tolerance via Aire-independent direct antigen presentation. AB - Peripheral immune tolerance is generally thought to result from cross presentation of tissue-derived proteins by quiescent tissue-resident dendritic cells to self-reactive T cells that have escaped thymic negative selection, leading to anergy or deletion. Recently, we and others have implicated the lymph node (LN) stroma in mediating CD8 T cell peripheral tolerance. We demonstrate that LN-resident lymphatic endothelial cells express multiple peripheral tissue antigens (PTAs) independent of the autoimmune regulator (Aire). They directly present an epitope derived from one of these, the melanocyte-specific protein tyrosinase, to tyrosinase-specific CD8 T cells, leading to their deletion. We also show that other LN stromal subpopulations express distinct PTAs by mechanisms that vary in their Aire dependence. These results establish lymphatic endothelial cells, and potentially other LN-resident cells, as systemic mediators of peripheral immune tolerance. PMID- 20308366 TI - Effects of inoculum, pH, and cations on the in vitro activity of fidaxomicin (OPT 80, PAR-101) against Clostridium difficile. AB - The effects of the inoculum, pH, cation concentrations, and different lots of commercial media on the in vitro susceptibility of Clostridium difficile to fidaxomicin were examined. Of the factors evaluated, only pH alterations influenced the activity of fidaxomicin against C. difficile, noticeably reducing its activity at higher pH (> or =7.9). PMID- 20308367 TI - Population pharmacokinetics of micafungin in neonates and young infants. AB - Micafungin is an echinocandin with potent activity against Candida spp. Hematogenous Candida meningoencephalitis (HCME) is a frequent complication of disseminated Candida infection in premature infants. A preclinical model of HCME suggests that micafungin may be an effective agent for this syndrome, but relatively high weight-based dosages are required. This prompted the further study of the safety and pharmacokinetics (PK) of micafungin in infants. Here, we describe the population pharmacokinetics of micafungin in 47 infants with a proven or presumptive diagnosis of disseminated candidiasis, who received 0.75, 1.5, 3, 7, 10, and 15 mg/kg of micafungin. The drug was infused daily, and samples were taken in the first dosing interval and at steady state. Serum concentrations were measured using high-performance liquid chromatography (HPLC). Data were modeled using an allometric pharmacokinetic model using a three-fourths scaling exponent for clearance and parameters normalized to a 70-kg adult. Drug exposures were estimated using Monte Carlo simulation. Optimal sampling times were determined using D-optimal design theory. The fit of the allometric model to the data was highly acceptable. The pharmacokinetics of micafungin were linear. The weight-normalized estimates of clearance and volume of distribution approximated those previously described for adults. The original population parameter values could be recapitulated in the Monte Carlo simulations. A dosage of 10 mg/kg/day resulted in 82.6% of patients with areas under the concentration time curve (AUCs) that are associated with near-maximal decline in fungal burden within the central nervous system (CNS). PMID- 20308368 TI - Homozygous triplicate mutations in three 16S rRNA genes responsible for high level aminoglycoside resistance in Nocardia farcinica clinical isolates from a Canada-wide bovine mastitis epizootic. AB - Nocardia farcinica strains showing high-level resistance to amikacin were isolated from clinical cases in a Canada-wide bovine mastitis epizootic. Shotgun cloning of the resistance genes in the amikacin-resistant mastitis isolate N. farcinica IFM 10580 (W6220 [Centers for Disease Control and Prevention]) using a multicopy vector system revealed that the 16S rRNA gene with an A-to-G single point mutation at position 1408 (in Escherichia coli numbering) conferred "moderate" cross-resistance to amikacin and other aminoglycosides to an originally susceptible N. farcinica strain IFM 10152. Subsequent DNA sequence analyses revealed that, in contrast to the susceptible strain, all three chromosomal 16S rRNA genes of IFM 10580, the epizootic clinical strain, contained the same A1408G point mutations. Mutant colonies showing high-level aminoglycoside resistance were obtained when the susceptible strain N. farcinica IFM 10152 was transformed with a multicopy plasmid carrying the A1408G mutant 16S rRNA gene and was cultured in the presence of aminoglycosides for 3 to 5 days. Of these transformants, at least two of the three chromosomal 16S rRNA genes contained A1408G mutations. A triple mutant was easily obtained from a strain carrying the two chromosomal A1408G mutant genes and one wild-type gene, even in the absence of the plasmid. The triple mutant showed the highest level of resistance to aminoglycosides, even in the absence of the plasmid carrying the mutant 16S rRNA gene. These results suggest that the homozygous mutations in the three 16S rRNA genes are responsible for the high-level aminoglycoside resistance found in N. farcinica isolates of the bovine mastitis epizootic. PMID- 20308369 TI - Raltegravir penetration in seminal plasma of healthy volunteers. PMID- 20308370 TI - Preclinical in vitro and in vivo characterization of the fully human monoclonal IgM antibody KBPA101 specific for Pseudomonas aeruginosa serotype IATS-O11. AB - Pseudomonas aeruginosa infection in ventilator-associated pneumonia is a serious and often life-threatening complication in intensive care unit patients, and new treatment options are needed. We used B-cell-enriched peripheral blood lymphocytes from a volunteer immunized with a P. aeruginosa O-polysaccharide toxin A conjugate vaccine to generate human hybridoma cell lines producing monoclonal antibodies specific for individual P. aeruginosa lipopolysaccharide serotypes. The fully human monoclonal antibody secreted by one of these lines, KBPA101, is an IgM/kappa antibody that binds P. aeruginosa of International Antigenic Typing System (IATS) serotype O11 with high avidity (5.81 x 10(7) M(-1) +/- 2.8 x 10(7) M(-1)) without cross-reacting with other serotypes. KBPA101 specifically opsonized the P. aeruginosa of IATS O11 serotype and mediated complement-dependent phagocytosis in vitro by the human monocyte-like cell line HL-60 at a very low concentration (half-maximal phagocytosis at 0.16 ng/ml). In vivo evaluation of KBPA101 demonstrated a dose-response relationship for protection against systemic infections in a murine burn wound sepsis model, where 70 to 100% of animals were protected against lethal challenges with P. aeruginosa at doses as low as 5 microg/animal. Furthermore, a high efficacy of KBPA101 in protection from local respiratory infections in an acute lung infection model in mice was demonstrated. Preclinical toxicology evaluation on human tissue, in rabbits, and in mice did not indicate any toxicity of KBPA101. Based on these preclinical findings, the first human clinical trials have been initiated. PMID- 20308371 TI - Impact of different carbapenems and regimens of administration on resistance emergence for three isogenic Pseudomonas aeruginosa strains with differing mechanisms of resistance. AB - We compared drugs (imipenem and doripenem), doses (500 mg and 1 g), and infusion times (0.5 and 1.0 [imipenem], 1.0 and 4.0 h [doripenem]) in our hollow-fiber model, examining cell kill and resistance suppression for three isogenic strains of Pseudomonas aeruginosa PAO1. The experiments ran for 10 days. Serial samples were taken for total organism and resistant subpopulation counts. Drug concentrations were determined by high-pressure liquid chromatography-tandem mass spectrometry (LC/MS/MS). Free time above the MIC (time > MIC) was calculated using ADAPT II. Time to resistance emergence was examined with Cox modeling. Cell kill and resistance emergence differences were explained, in the main, by differences in potency (MIC) between doripenem and imipenem. Prolonged infusion increased free drug time > MIC and improved cell kill. For resistance suppression, the 1-g, 4-h infusion was able to completely suppress resistance for the full period of observation for the wild-type isolate. For the mutants, control was ultimately lost, but in all cases, this was the best regimen. Doripenem gave longer free time > MIC than imipenem and, therefore, better cell kill and resistance suppression. For the wild-type organism, the 1-g, 4-h infusion regimen is preferred. For organisms with resistance mutations, larger doses or addition of a second drug should be studied. PMID- 20308373 TI - Susceptibility of recently collected Spanish pneumococci nonsusceptible to oral penicillin from serotypes not included in the 7-valent conjugate vaccine. AB - The susceptibilities of pneumococci recently collected (up to June 2009) in Spain (500 isolates nonsusceptible to oral penicillin and 150 susceptible isolates) from serotypes not included in the conjugate vaccine were determined. Most nonsusceptible isolates (53.6%) belonged to serotype 19A. Susceptibility rates in serotype 19A penicillin-intermediate (n = 201)/penicillin-resistant (n = 67) isolates were <33%/< or =6.0% (erythromycin and oral cephalosporins with defined breakpoints), 85.1%/11.9% (amoxicillin), and 96.0%/52.2% (cefotaxime), respectively. Low susceptibility to common oral beta-lactams was also found in serotypes 11A (95.5% susceptibility to cefotaxime and erythromycin) and 35B. PMID- 20308372 TI - Novel synthetic, salt-resistant analogs of human beta-defensins 1 and 3 endowed with enhanced antimicrobial activity. AB - Human beta-defensins (hBDs) are antimicrobial peptides of human innate immunity. The antibacterial activities of hBDs 1, 2, and 4 but not the activity of hBD3 are impaired by high salt levels. We have designed and synthesized seven novel hBD analogs, constituted by different domains of hBD1 (which is constitutively expressed in humans) and of hBD3 (which is induced by microorganisms and inflammatory factors in humans), that would maintain and potentially increase the wild-type antimicrobial activities and be salt resistant. We have compared the antibacterial, antiviral, and chemotactic activities of the analogs with those of hBD1 and hBD3. We show that the hBD1 internal region and the hBD3 C-terminal region are critical for antibacterial activity also at high salt concentrations, whereas deletion of the N-terminal region of hBD3 results in an increase in antibacterial activity. All analogs inhibited herpes simplex virus; antiviral activity was enhanced by the hBD1 internal region and the hBD3 C-terminal region. Wild-type and analog peptides were chemotactic for granulocytes and monocytes, irrespective of the salt concentrations. These new peptides may have therapeutic potential. PMID- 20308374 TI - Activity of ceftaroline against recent emerging serotypes of Streptococcus pneumoniae in the United States. AB - The in vitro activity of ceftaroline against 891 pneumococci collected in 2008 from 22 centers in the United States was investigated. Ceftaroline was the most potent agent tested, with the MICs being <0.008 to 0.5 microg/ml and the MIC(90)s being <0.008 to 0.25 microg/ml against 11 prevailing serotypes. The overall rates of susceptibility were as follows: penicillin G, 86.2%; ceftriaxone, 90.7%; cefuroxime, 70.1%; erythromycin, 61.6%; clindamycin, 79.2%; levofloxacin, 99.4%; and vancomycin, 100%. Serotype 19A isolates were the least susceptible. These results support the use of ceftaroline for the treatment of pneumococcal infections, including those caused by pneumococci resistant to other agents. PMID- 20308375 TI - Combined antibacterial and anti-inflammatory activity of a cationic disubstituted dexamethasone-spermine conjugate. AB - The rising number of antibiotic-resistant bacterial strains represents an emerging health problem that has motivated efforts to develop new antibacterial agents. Endogenous cationic antibacterial peptides (CAPs) that are produced in tissues exposed to the external environment are one model for the design of novel antibacterial compounds. Here, we report evidence that disubstituted dexamethasone-spermine (D2S), a cationic corticosteroid derivative initially identified as a by-product of synthesis of dexamethasone-spermine (DS) for the purpose of improving cellular gene delivery, functions as an antibacterial peptide-mimicking molecule. This moiety exhibits bacterial killing activity against clinical isolates of Staphylococcus aureus, Pseudomonas aeruginosa present in cystic fibrosis (CF) sputa, and Pseudomonas aeruginosa biofilm. Although compromised in the presence of plasma, D2S antibacterial activity resists the proteolytic activity of pepsin and is maintained in ascites, cerebrospinal fluid, saliva, and bronchoalveolar lavage (BAL) fluid. D2S also enhances S. aureus susceptibility to antibiotics, such as amoxicillin (AMC), tetracycline (T), and amikacin (AN). Inhibition of interleukin-6 (IL-6) and IL-8 release from lipopolysaccharide (LPS)- or lipoteichoic acid (LTA)-treated neutrophils in the presence of D2S suggests that this molecule might also prevent systemic inflammation caused by bacterial wall products. D2S-mediated translocation of green fluorescent protein (GFP)-labeled glucocorticoid receptor (GR) in bovine aorta endothelial cells (BAECs) suggests that some of its anti inflammatory activities involve engagement of glucocorticoid receptors. The combined antibacterial and anti-inflammatory activities of D2S suggest its potential as an alternative to natural CAPs in the prevention and treatment of some bacterial infections. PMID- 20308376 TI - Mutant prevention concentrations of four carbapenems against gram-negative rods. AB - We tested the propensities of four carbapenems to select for resistant Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Acinetobacter baumannii mutants by determining the mutant prevention concentrations (MPCs) for 100 clinical strains with various ss-lactam phenotypes. Among the members of the Enterobacteriaceae family and A. baumannii strains, the MPC/MIC ratios were mostly 2 to 4. In contrast, for P. aeruginosa the MPC/MIC ratios were 4 to > or =16. The MPC/MIC ratios for beta-lactamase-positive K. pneumoniae and E. coli isolates were much higher (range, 4 to >16 microg/ml) than those for ss-lactamase-negative strains. PMID- 20308377 TI - Telbivudine exhibits no inhibitory activity against HIV-1 clinical isolates in vitro. AB - Most approved drugs with activity against hepatitis B virus (HBV) have activity against human immunodeficiency virus type 1 (HIV-1), which precludes their use in patients who are coinfected with HBV and HIV-1 and who are not receiving antiretroviral therapy due to the risk of inducing resistance. The activity of telbivudine, a highly selective HBV inhibitor, against temporally and geographically distinct wild-type and multidrug-resistant HIV-1 clinical isolates was evaluated in vitro. No inhibition was observed with up to 600 muM drug, which supports further exploration of telbivudine as a therapeutic option for the treatment of HBV infections in patients coinfected with HIV-1. PMID- 20308378 TI - Systematic review and meta-analysis of the tolerability and hepatotoxicity of antifungals in empirical and definitive therapy for invasive fungal infection. AB - To evaluate the tolerability and liver safety profiles of the systemic antifungal agents commonly used for the treatment of invasive fungal infection, we conducted a systematic review and meta-analysis of randomized controlled trials published before 31 August 2009. Two reviewers independently applied selection criteria, performed quality assessment, and extracted data. We used the beta-binomial model to account for variation across studies and the maximum likelihood method to estimate the pooled risks. We identified 39 studies with more than 8,000 enrolled patients for planned comparisons. The incidence rates of treatment discontinuation due to adverse reactions and liver injury associated with antifungal therapy ranged widely. The pooled risks of treatment discontinuation due to adverse reactions were above 10% for amphotericin B formulations and itraconazole, whereas they were 2.5% to 3.8% for fluconazole, caspofungin, and micafungin. We found that 1.5% of the patients stopped itraconazole treatment due to hepatotoxicity. Furthermore, 19.7% of voriconazole users and 17.4% of itraconazole users had elevated serum liver enzyme levels, although they did not require treatment discontinuation, whereas 2.0% or 9.3% of fluconazole and echinocandin users had elevated serum liver enzyme levels but did not require treatment discontinuation. The results were similar when we stratified the data by empirical or definitive antifungal therapy. Possible explanations for antifungal agent-related hepatotoxicity were confounded by antifungal prescription to patients with a high risk of liver injury, the increased chance of detection of hepatotoxicity due to prolonged treatment, or the pharmacological entity. PMID- 20308379 TI - In vitro properties of BAL30072, a novel siderophore sulfactam with activity against multiresistant gram-negative bacilli. AB - BAL30072 is a new monocyclic beta-lactam antibiotic belonging to the sulfactams. Its spectrum of activity against significant Gram-negative pathogens with beta lactam-resistant phenotypes was evaluated and was compared with the activities of reference drugs, including aztreonam, ceftazidime, cefepime, meropenem, imipenem, and piperacillin-tazobactam. BAL30072 showed potent activity against multidrug resistant (MDR) Pseudomonas aeruginosa and Acinetobacter sp. isolates, including many carbapenem-resistant strains. The MIC(90)s were 4 microg/ml for MDR Acinetobacter spp. and 8 microg/ml for MDR P. aeruginosa, whereas the MIC(90) of meropenem for the same sets of isolates was >32 microg/ml. BAL30072 was bactericidal against both Acinetobacter spp. and P. aeruginosa, even against strains that produced metallo-beta-lactamases that conferred resistance to all other beta-lactams tested, including aztreonam. It was also active against many species of MDR isolates of the Enterobacteriaceae family, including isolates that had a class A carbapenemase or a metallo-beta-lactamase. Unlike other monocyclic beta-lactams, BAL30072 was found to trigger the spheroplasting and lysis of Escherichia coli rather than the formation of extensive filaments. The basis for this unusual property is its inhibition of the bifunctional penicillin-binding proteins PBP 1a and PBP 1b, in addition to its high affinity for PBP 3, which is the target of monobactams, such as aztreonam. PMID- 20308380 TI - Characterization of CSP-1, a novel extended-spectrum beta-lactamase produced by a clinical isolate of Capnocytophaga sputigena. AB - The Capnocytophaga sputigena isolate NOR, responsible for septicemia, was resistant to amoxicillin and narrow-spectrum cephalosporins. In a cloning experiment, a new gene, bla(CSP-1), was identified; this gene encodes a novel extended-spectrum beta-lactamase (ESBL) that shares only 52% and 49% identities with the CME-1 and VEB-1 beta-lactamases, respectively. The G+C content of this gene, its genetic environment, the absence of conjugation transfer, and its detection in two reference strains suggested that it was an intrinsic resistance gene located on the chromosome. PMID- 20308381 TI - Preclinical characterization of the antiviral activity of SCH 900518 (narlaprevir), a novel mechanism-based inhibitor of hepatitis C virus NS3 protease. AB - Small-molecule hepatitis C virus (HCV) NS3 protease inhibitors such as boceprevir (SCH 503034) have been shown to have antiviral activity when they are used as monotherapy and in combination with pegylated alpha interferon and ribavirin in clinical trials. Improvements in inhibitor potency and pharmacokinetic properties offer opportunities to increase drug exposure and to further increase the sustained virological response. Exploration of the structure-activity relationships of ketoamide inhibitors related to boceprevir has led to the discovery of SCH 900518, a novel ketoamide protease inhibitor which forms a reversible covalent bond with the active-site serine. It has an overall inhibition constant (K*(i)) of 7 nM and a dissociation half-life of 1 to 2 h. SCH 900518 inhibited replicon RNA at a 90% effective concentration (EC(90)) of 40 nM. In biochemical assays, SCH 900518 was active against proteases of genotypes 1 to 3. A 2-week treatment with 5x EC(90) of the inhibitor reduced the replicon RNA level by 3 log units. Selection of replicon cells with SCH 900518 resulted in the outgrowth of several resistant mutants (with the T54A/S and A156S/T/V mutations). Cross-resistance studies demonstrated that the majority of mutations for resistance to boceprevir and telaprevir caused similar fold losses of activity against all three inhibitors; however, SCH 900518 retained more activity against these mutants due to its higher intrinsic potency. Combination treatment with alpha interferon enhanced the inhibition of replicon RNA and suppressed the emergence of resistant replicon colonies, supporting the use of SCH 900518 pegylated alpha interferon combination therapy in the clinic. In summary, the results of the preclinical characterization of the antiviral activity of SCH 900518 support its evaluation in clinical studies. PMID- 20308382 TI - Phenotypic susceptibility to bevirimat in isolates from HIV-1-infected patients without prior exposure to bevirimat. AB - Bevirimat (BVM) is the first of a new class of anti-HIV drugs with a novel mode of action known as maturation inhibitors. BVM inhibits the last cleavage of the Gag polyprotein by HIV-1 protease, leading to the accumulation of the p25 capsid small peptide 1 (SP1) intermediate and resulting in noninfectious HIV-1 virions. Early clinical studies of BVM showed that over 50% of the patients treated with BVM did not respond to treatment. We investigated the impact of prior antiretroviral (ARV) treatment and/or natural genetic diversity on BVM susceptibility by conducting in vitro phenotypic analyses of viruses made from patient samples. We generated 31 recombinant viruses containing the entire gag and protease genes from 31 plasma samples from HIV-1-infected patients with (n = 21) or without (n = 10) prior ARV experience. We found that 58% of the patient isolates tested had a >10-fold reduced susceptibility to BVM, regardless of the patient's ARV experience or the level of isolate resistance to protease inhibitors. Analysis of mutants with site-directed mutations confirmed the role of the V370A SP1 polymorphism (SP1-V7A) in resistance to BVM. Furthermore, we demonstrated for the first time that a capsid polymorphism, V362I (CA protein V230I), is also a major mutation conferring resistance to BVM. In contrast, none of the previously defined resistance-conferring mutations in Gag selected in vitro (H358Y, L363M, L363F, A364V, A366V, or A366T) were found to occur among the viruses that we analyzed. Our results should be helpful in the design of diagnostics for prediction of the potential benefit of BVM treatment in HIV-1 infected patients. PMID- 20308383 TI - Characterization of DIM-1, an integron-encoded metallo-beta-lactamase from a Pseudomonas stutzeri clinical isolate in the Netherlands. AB - A carbapenem-resistant Pseudomonas stutzeri strain isolated from a Dutch patient was analyzed in detail. This isolate produced a metallo-beta-lactamase (MBL) whose gene, with 43.5% GC content, was cloned and expressed in Escherichia coli. beta-Lactamase DIM-1 (for Dutch imipenemase) was weakly related to other Ambler class B beta-lactamases, sharing <52% amino acid identity with the most closely related MBL, GIM-1, and 45% identity with IMP-type MBLs. The beta-Lactamase DIM-1 significantly hydrolyzed broad-spectrum cephalosporins and carbapenems and spared aztreonam. This MBL gene was embedded in a class 1 integron containing two other gene cassettes, encoding resistance to aminoglycosides and disinfectants, that was located on a 70-kb plasmid. PMID- 20308384 TI - The M230L nonnucleoside reverse transcriptase inhibitor resistance mutation in HIV-1 reverse transcriptase impairs enzymatic function and viral replicative capacity. AB - The M230L mutation in HIV-1 reverse transcriptase (RT) is associated with resistance to first-generation nonnucleoside reverse transcriptase inhibitors (NNRTIs). The present study was designed to determine the effects of M230L on enzyme function, viral replication capacity (RC), and the extent to which M230L might confer resistance to the second-generation NNRTI etravirine (ETR) as well as to the first-generation NNRTIs efavirenz (EFV) and nevirapine (NVP). Phenotyping assays with TZM-bl cells confirmed that M230L conferred various degrees of resistance to each of the NNRTIs tested. Recombinant viruses containing M230L displayed an 8-fold decrease in RC compared to that of the parental wild-type (WT) virus. Recombinant HIV-1 WT and M230L mutant RT enzymes were purified; and both biochemical and cell-based phenotypic assays confirmed that M230L conferred resistance to each of EFV, NVP, and ETR. RT that contained M230L was also deficient in regard to each of minus-strand DNA synthesis, both DNA- and RNA-dependent polymerase activities, processivity, and RNase H activity, suggesting that this mutation contributes to diminished viral replication kinetics. PMID- 20308385 TI - Novel mechanism of glycopeptide resistance in the A40926 producer Nonomuraea sp. ATCC 39727. AB - In glycopeptide-resistant enterococci and staphylococci, high-level resistance is achieved by replacing the C-terminal d-alanyl-d-alanine of lipid II with d-alanyl d-lactate, thus reducing glycopeptide affinity for cell wall targets. Reorganization of the cell wall in these organisms is directed by the vanHAX gene cluster. Similar self-resistance mechanisms have been reported for glycopeptide producing actinomycetes. We investigated glycopeptide resistance in Nonomuraea sp. ATCC 39727, the producer of the glycopeptide A40926, which is the precursor of the semisynthetic antibiotic dalbavancin, which is currently in phase III clinical trials. The MIC of Nonomuraea sp. ATCC 39727 toward A40926 during vegetative growth was 4 microg/ml, but this increased to ca. 20 microg/ml during A40926 production. vanHAX gene clusters were not detected in Nonomuraea sp. ATCC 39727 by Southern hybridization or by PCR with degenerate primers. However, the dbv gene cluster for A40926 production contains a gene, vanY (ORF7), potentially encoding an enzyme capable of removing the terminal d-Ala residue of pentapeptide peptidoglycan precursors. Analysis of UDP-linked peptidoglycan precursors in Nonomuraea sp. ATCC 39727 revealed the predominant presence of the tetrapeptide UDP-MurNAc-l-Ala-d-Glu-meso-Dap-d-Ala and only traces of the pentapeptide UDP MurNAc-l-Ala-d-Glu-meso-Dap-d-Ala-d-Ala. This suggested a novel mechanism of glycopeptide resistance in Nonomuraea sp. ATCC 39727 that was based on the d,d carboxypeptidase activity of vanY. Consistent with this, a vanY-null mutant of Nonomuraea sp. ATCC 39727 demonstrated a reduced level of glycopeptide resistance, without affecting A40926 productivity. Heterologous expression of vanY in a sensitive Streptomyces species, Streptomyces venezuelae, resulted in higher levels of glycopeptide resistance. PMID- 20308386 TI - Intra- and extracellular activities of dicloxacillin against Staphylococcus aureus in vivo and in vitro. AB - Antibiotic treatment of Staphylococcus aureus infections is often problematic due to the slow response and recurrences. The intracellular persistence of the staphylococci offers a plausible explanation for the treatment difficulties because of the impaired intracellular efficacies of the antibiotics. The intra- and extracellular time- and concentration-kill relationships were examined in vitro with THP-1 cells and in vivo by use of a mouse peritonitis model. The in vivo model was further used to estimate the most predictive pharmacokinetic/pharmacodynamic (PK/PD) indices (the ratio of the maximum concentration of drug in plasma/MIC, the ratio of the area under the concentration-time curve/MIC, or the cumulative percentage of a 24-h period that the free [f] drug concentration exceeded the MIC under steady-state pharmacokinetic conditions [fT(MIC)]) for dicloxacillin (DCX) intra- and extracellularly. In general, DCX was found to have similar intracellular activities, regardless of the model used. Both models showed (i) the relative maximal efficacy (1-log-unit reduction in the numbers of CFU) of DCX intracellularly and (ii) the equal relative potency of DCX intra- and extracellularly, with the MIC being a good indicator of the overall response in both situations. Discordant results, based on data obtained different times after dosing, were obtained from the two models when the extracellular activity of DCX was measured, in which the in vitro model showed a considerable reduction in the number of CFU from that in the original inoculum (3-log-unit decrease in the number of CFU after 24 h), whereas the extracellular CFU reduction achieved in vivo after 4 h did not exceed 1 log unit. Multiple dosing of DCX in vivo revealed increased extra- and intracellular efficacies (2.5 log and 2 log units of reduction in the numbers of CFU after 24 h, respectively), confirming that DCX is a highly active antistaphylococcal antibiotic. PK/PD analysis revealed that fT(MIC) is the index that is the most predictive of the outcome of infection both intra- and extracellularly. PMID- 20308387 TI - Plasmodium vivax susceptibility to ferroquine. AB - The novel organometallic chloroquine analog ferroquine (SSR 97193) is effective against chloroquine-resistant Plasmodium falciparum. The ex vivo efficacy of ferroquine against Plasmodium vivax isolates was tested. Ferroquine has a potent ex vivo effect on P. vivax schizont maturation (median 50% inhibitory concentration, 15 nM; n = 42). No significant cross-sensitivity between ferroquine and other antimalarials was detected. This drug may be a suitable replacement for chloroquine in the treatment of drug-resistant P. vivax malaria. PMID- 20308388 TI - Origins of the recent emergence of Plasmodium falciparum pyrimethamine resistance alleles in Madagascar. AB - The combination of sulfadoxine-pyrimethamine is recommended for use as intermittent preventive treatment of malaria during pregnancy and is deployed in Africa. The emergence and the spread of resistant parasites are major threats to such an intervention. We have characterized the Plasmodium falciparum dhfr (pfdhfr) haplotypes and flanking microsatellites in 322 P. falciparum isolates collected from the Comoros Islands and Madagascar. One hundred fifty-six (48.4%) carried the wild-type pfdhfr allele, 19 (5.9%) carried the S108N single-mutation allele, 30 (9.3%) carried the I164L single-mutation allele, 114 (35.4%) carried the N51I/C59R/S108N triple-mutation allele, and 3 (1.0%) carried the N51I/C59R/S108N/I164L quadruple-mutation allele. Microsatellite analysis showed the introduction from the Comoros Islands of the ancestral pfdhfr triple mutant allele of Asian origin and its spread in Madagascar. Evidence for the emergence on multiple occasions of the I164L single-mutation pfdhfr allele in Madagascar was also obtained. Thus, the conditions required to generate mutants with quadruple mutations are met in Madagascar, representing a serious threat to current drug policy. PMID- 20308389 TI - Cure of Listeria monocytogenes meningitis after early transition to oral therapy. PMID- 20308391 TI - In vitro activity of fidaxomicin (OPT-80) tested against contemporary clinical isolates of Staphylococcus spp. and Enterococcus spp. PMID- 20308390 TI - In vitro activity of ACH-702, a new isothiazoloquinolone, against Nocardia brasiliensis compared with econazole and the carbapenems imipenem and meropenem alone or in combination with clavulanic acid. AB - The in vitro activities of ACH-702 and other antimicrobials against 30 Nocardia brasiliensis isolates were tested. The MIC(50) (MIC for 50% of the strains tested) and MIC(90) values of ACH-702 were 0.125 and 0.5 microg/ml. The same values for econazole were 2 and 4 microg/ml. The MIC(50) and MIC(90) values of imipenem and meropenem were 64 and >64 microg/ml and 2 and 8 microg/ml, respectively; the addition of clavulanic acid to the carbapenems had no effect. PMID- 20308393 TI - Evidence that maternal conjugated linoleic acid negatively affects lipid uptake in late-stage chick embryos resulting in increased embryonic mortality. AB - An experiment was performed to determine the effect of maternal dietary conjugated linoleic acid (CLA) on growth and composition of surviving chick embryos and residual yolk sacs during the last week of development when lipid utilization becomes prevalent. After 14 d on experimental diets, hatchability of non-cooled eggs obtained from CLA-fed hens (0.5% of the diet) was 10%, where 20% of surviving CLA embryos died after d 13 of incubation. Hatchability was 93% for controls and only 4.36% of mortality occurred after d 13 of incubation. Decline in yolk sac weight in control embryos (0.75 g/d) was significantly greater than that from viable CLA embryos (0.51 g/d). Growth rate (2.6 g/d) of surviving embryos from d 13 to 20 was reduced in CLA embryos in comparison to growth rate of controls (3.0 g/d). Relative proportion of lipid in residual yolk sacs in embryos from control-fed hens decreased from 26.72% (d 13) to 15.94% (d 19) during incubation, whereas little change was evident in residual yolk sac from CLA embryos on d 13 (21.52%) to d 19 (20.39%). Fatty acid analysis of residual yolk sac contents suggested that transport of fatty acids from the contents (liquid yolk) to the yolk sac membrane was not impaired in CLA embryos, as shown by a similar pattern in reduction of total fatty acids in residual yolk sac contents between treatment groups. Apart from 18:1n-9 (d 17), there were no consistent differences in the fatty acid content between embryos from hens fed the control diet or the CLA diet at any time point. Maternal CLA led to increased 18:0 and decreased 18:1n-9 in yolk lipid and embryonic tissues compared with controls across time. These findings could possibly suggest that CLA embryos had less capacity to use yolk lipids from the residual yolk sac during the last week of incubation. PMID- 20308394 TI - Short-term spatial memory responses in aged Japanese quail selected for divergent adrenocortical stress responsiveness. AB - Stress-induced glucocorticoids can dampen learning and spatial memory via neuronal damage to the hippocampus. Cognition losses can be transient (associated with acute stress episodes) or permanent as in aged individuals who show chronic glucocorticoid-induced accelerated brain aging and neurodegeneration (dementia). Thus, chronic versus acute stress effects on spatial memory responses of quail selected for reduced (low stress, LS) or exaggerated (high stress, HS) plasma corticosterone (B) response to brief restraint were assessed. Aged food-motivated male LS and HS quail were tested for 10 min in a feed-baited 8-arm radial arm maze (RAM) 1) at 255 d of age (quail who had experienced lifelong management stressors but who were otherwise never intentionally stressed; that is, chronically stressed birds), 2) on the next day post-acute stressor treatment (5 min of restraint), and 3) on the next day without treatment (acute stress recovery). The RAM tests used the win-shift procedure in which visited arms were not rebaited. Radial arm maze performance was measured by determination of the total number of arm choices made, the number of correct entries made into baited arms out of the first 8 choices, the time required to make a choice, and the number of pellets eaten. Line effects (P < 0.001 in all cases) were detected for total number of arm choices made (HS < LS), number of correct entries made into baited arms out of the first 8 choices (HS < LS), time required to make a choice (HS > LS), and number of pellets eaten (HS < LS). However, neither the effects of day of RAM testing nor its interaction with line further influenced these variables. Thus, although selection for divergent plasma B responsiveness to an acute stressor was found to be associated with severe impairment of spatial memory in aged male HS compared with LS quail, the observed spatial memory impairments (HS > LS) could not be further altered by acute stressor treatment. Line differences in cognition may reflect lifelong management-induced stress episodes that periodically produce higher plasma B responses in HS than LS quail, which underlie HS quail memory deficits, or other etiologies, or both. PMID- 20308395 TI - Short- and long-term movement patterns in complex confined environments in broiler chickens: the effects of distribution of cover panels and food resources. AB - In captivity, the positioning of structural enrichment and food resources influences behavior and space use. The aim of this experiment was to examine the influence of cover panels and the positioning of food resources on the movement and space use of domestic fowl (Gallus gallus domesticus). Eight groups of 45 male chickens were used for this study. Each group was temporarily divided into 2 groups of 20 birds; each group was used to investigate the influence of cover panels and the effects of food resources. In the cover panel treatments, 20 birds were placed in the 10-m(2) testing enclosures that contained one 2-m cover panel in the center, four 0.5-m panels in a zigzag fashion, or had no panels (controls). In the food resource treatments, the position of the feed trays varied, with 1 feed tray in the center; 2 feed trays, one at each edge; or 4 feed trays, one at each corner of the enclosure. Locations of focal birds were collected through instantaneous scan sampling that was recorded as X,Y coordinates. From these X,Y coordinates, we calculated net and total distance moved, mean and maximum step lengths, and angular dispersion of the path of movement. To calculate long-term space use, 3 replications for each of 3 cover panel and food resource treatments were placed in nine 10-m(2) enclosures for 1 wk. Locations of focal birds in each group were collected by ad libitum scan sampling and data were used to calculate core areas by kernel estimates. Mixed model ANOVA was used to determine the effects of the distribution of cover panels and positioning of food resources on movement parameters during the study period, whereas 1-way ANOVA was used for core areas. Surprisingly, our analyses showed that long-term and short-term movement was not affected by changing the location of cover panels or food resources. Only net distance seemed to be affected to a certain degree by the presence of the cover and the distinctive availability of food resources. PMID- 20308396 TI - Genotypes of chicken major histocompatibility complex B locus associated with regression of Rous sarcoma virus J-strain tumors. AB - The chicken MHC-B locus affects the response to several strains of Rous sarcoma virus (RSV). We evaluated the association between haplotypes of the MHC-B locus and responses to the J strain of RSV by using an F(2) experimental resource family constructed with tumor-regressive (White Leghorn) and tumor-progressive (Rhode Island Red) chickens. The MHC-B haplotypes were determined by genotyping of the microsatellite marker LEI0258 and MHC-B locus class I alpha chain 2 (BF2). Two haplotypes in the resource family, one associated with tumor regression and one with progression, were defined by these 2 markers. To discriminate more precisely the regressive haplotype in this family, we further developed 35 SNP markers at the MHC-B locus. Information on the haplotypes revealed here should be useful for identifying chickens with regression and progression phenotypes of J strain RSV-induced tumors. PMID- 20308397 TI - Evaluation of inbreeding in laying hens by applying optimum genetic contribution and gene flow theory. AB - Due to consistent increases of inbreeding of on average 0.95% per generation in layer populations, selection tools should consider both genetic gain and genetic relationships in the long term. The optimum genetic contribution theory using official estimated breeding values for egg production was applied for 3 different lines of a layer breeding program to find the optimal allocations of hens and sires. Constraints in different scenarios encompassed restrictions related to additive genetic relationships, the increase of inbreeding, the number of selected sires and hens, and the number of selected offspring per mating. All these constraints enabled higher genetic gain up to 10.9% at the same level of additive genetic relationships or in lower relationships at the same gain when compared with conventional selection schemes ignoring relationships. Increases of inbreeding and genetic gain were associated with the number of selected sires. For the lowest level of the allowed average relationship at 10%, the optimal number of sires was 70 and the estimated breeding value for egg production of the selected group was 127.9. At the highest relationship constraint (16%), the optimal number of sires decreased to 15, and the average genetic value increased to 139.7. Contributions from selected sires and hens were used to develop specific mating plans to minimize inbreeding in the following generation by applying a simulated annealing algorithm. The additional reduction of average additive genetic relationships for matings was up to 44.9%. An innovative deterministic approach to estimate kinship coefficients between and within defined selection groups based on gene flow theory was applied to compare increases of inbreeding from random matings with layer populations undergoing selection. Large differences in rates of inbreeding were found, and they underline the necessity to establish selection tools controlling long-term relationships. Furthermore, it was suggested to use optimum genetic contribution theory for conservation schemes or, for example, the experimental line in our study. PMID- 20308398 TI - Histopathology, immunohistochemistry, in situ apoptosis, and ultrastructure characterization of the digestive and lymphoid organs of new type gosling viral enteritis virus experimentally infected gosling. AB - Here, for the first time, to colocalize new type gosling viral enteritis virus (NGVEV) with histological lesions and in situ apoptosis in the digestive organs (esophagus, proventriculus, gizzard, small intestine, cecum, rectum, liver, and pancreas) and the lymphoid organs (bursa of Fabricius, thymus, Harderian gland, and spleen) of experimentally infected goslings, portions of tissues were collected at sequential infection time points and examined by histopathology for histological lesions, immunohistochemical staining for viral antigens, ultrastructural observation by transmission electron microscope (TEM) for virus particles and apoptotic cells, and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling assay for in situ apoptosis. The hyperemia, hemorrhage, infiltration of lymphocytes, progressive lymphoid depletion, apoptosis, and necrosis were readily observed in the lymphoid organs and intestine tract by histopathological examination. The NGVEV particles and viral antigens widely appeared in the small intestine and bursa of Fabricius as early as 2 d postinfection (PI) by TEM and immunohistochemical staining, and the presence and quantity of it reached a maximum during 6 to 12 d PI. The principal sites for NGVEV were endothelial cells, epithelia, mucosal cells, glandular cells, fibrocytes, macrophages, and lymphocytes. A series of apoptotic morphological changes including chromatin condensation and margination, cytoplasmic shrinkage, and formation of apoptotic body were observed by TEM, and the number of apoptotic cells was largely increased from 4 d PI and peaked at 9 d PI by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling analysis. The histological organ lesions and apoptosis in vivo were generally associated with sites of NGVEV localization, which can be regarded as the cause of death. This work may shed light on the pathogenesis of new type gosling viral enteritis and put new insight into the pathogenesis of goose adenovirus. PMID- 20308399 TI - Effect of the duration of prefeeding on amino acid digestibility of wheat distillers dried grains with solubles in broiler chicken. AB - The objective of this study was to determine the effect of the duration of prefeeding on prececal amino acid (AA) digestibility of wheat distillers dried grains with solubles (DDGS) in broilers. The experimental diets with DDGS at levels of 0, 10, and 20% were offered ad libitum for 7, 5, and 3 d, starting on 14, 16, and 18 d of age. Titanium dioxide was used as an indigestible marker. Six pens of 10 birds were allocated to each treatment. Digesta was sampled on a pen basis from the distal two-thirds of the intestine section between Meckel's diverticulum and 2 cm anterior to the ileo-ceca-colonic junction. Ingested and digested amounts of AA were determined for each pen. Digestibility of AA in the diets was not significantly affected by the duration of prefeeding but was significantly reduced by inclusion of DDGS. Digestibility of AA in DDGS was determined by using a linear regression approach. The digestibility of AA in DDGS ranged from 76% (Arg, 5 d of feeding) to 33% (Asp, 3 d of feeding). There was no significant effect of prefeeding time on AA digestibility of DDGS. Lysine digestibility of DDGS was 72%. The mean digestibility of the AA Arg, Cys, Ile, Leu, Lys, Met, Phe, Thr, and Val of DDGS across the 3 prefeeding times was 66%. This study gave evidence that 3 d of prefeeding a diet is sufficient in studying prececal AA digestibility in broilers when low-digestible feeds are used. PMID- 20308400 TI - Characterization of folate-dependent enzymes and indices of folate status in laying hens supplemented with folic acid or 5-methyltetrahydrofolate. AB - The conversion of folic acid (FA) to the biologically active 5 methyltetrahydrofolate (5-MTHF) is necessary for the deposition of folate in the egg. A study was conducted to compare egg folate concentrations, indices of folate status, and activities of folate-dependent enzymes in response to equimolar intake of either FA or 5-MTHF in laying hens. Forty-eight laying hens, 24 wk of age, from 2 different strains (Shaver White and Shaver Brown) were randomly assigned to receive 1 of 3 (n = 8 per strain) dietary treatments: 1) basal diet with no supplemental folate, 2) basal diet + 10 mg/kg of FA, or 3) basal diet + 11.3 mg/kg of 5-MTHF for 3 wk. A completely randomized design with 3 dietary treatments and 2 laying hen strains in a 3 x 2 factorial arrangement was used. Data were subjected to ANOVA, using the PROC GLM procedure of SAS. Plasma homocysteine, serum, and egg folate concentrations; hepatic serine hydroxymethyltransferase; and methionine synthase activity were affected by dietary folate supplementation but not by its form (FA and 5-MTHF). Relative to control hens, plasma homocysteine was decreased (P < 0.05) by 14.2%, whereas serum and egg folate were increased (P < 0.05) by 78.3 and 61.8%, respectively, in hens consuming either folate compound. Hepatic serine hydroxymethyltransferase and methionine synthase activity were increased and decreased (P < 0.05), respectively, in folate-fed birds compared with control-fed birds. Hepatic dihydrofolate reductase was influenced by both the addition and form of dietary folate, being higher (P < 0.05) in FA-fed birds than in 5-MTHF and control-fed birds. Feed efficiency was improved (P < 0.05) in 5-MTHF-fed birds relative to FA fed birds. Strain of hen influenced serum folate and plasma homocysteine concentrations but not other indices of folate metabolism. Overall, FA and 5-MTHF have equivalent effects in enhancing egg folate concentrations and improving folate status in laying hens. Also, supplementation and form of folate may modulate the activity of folate-dependent enzymes. PMID- 20308401 TI - Regulation of chick bone growth by leptin and catecholamines. AB - Leptin and the sympathetic nervous system have a unique role in linking nutritional status to skeletal metabolism in mammals. Such a regulatory mechanism has not been identified in birds but would be beneficial to signal information about energy reserves to an organ system essential for locomotion, reproduction, and survival. To explore this potential role of leptin and the sympathetic nervous system in birds, an ex vivo chick tibiotarsal model was used to test the effects of leptin and sympathetic activity on longitudinal bone growth and the expression of chondrocyte markers. Reverse transcription-PCR analysis revealed the expression of chicken leptin receptor mRNA as well as both alpha-adrenergic (alpha1A, alpha2A, alpha2B, alpha2C) and beta adrenergic (beta1, beta2) receptor subtype mRNA in the whole bone. Incubation with norepinephrine (NE; 0, 10, or 100 microM for 4 d) caused a significant increase in distal condyle length as compared with vehicle-treated, contralateral tibiotarsi. In contrast, no change in condyle length was detected after leptin treatment (0 or 10 nM or 1 microM for 4 d). Analysis of cell proliferation by bromodeoxyuridine incorporation revealed no increase in bromodeoxyuridine-positive cells in the condyles in response to leptin or NE treatments. Real-time PCR analysis showed that NE enhanced type X collagen mRNA expression, a marker of mature hypertrophic chondrocytes, with no effect on type II collagen mRNA, the matrix protein secreted by proliferating chondrocytes. Leptin treatment had no effect on the expression of either matrix protein. Treatment with agonists specific for alpha- or beta-adrenergic receptors indicates that the activation of alpha-adrenergic receptors is most likely responsible for the sympathetic effect on type X collagen gene expression. These results suggest that NE and other sympathetic agonists have positive effects on bone elongation and the changes in critical genes associated with this process. These neurotransmitters may facilitate this by promoting chondrocyte maturation. These studies represent novel evidence suggesting a role of sympathetic tone in the regulation of skeletal growth in avian species. PMID- 20308402 TI - Changes in satellite cell proliferation and differentiation during turkey muscle development. AB - Posthatch muscle growth is determined by the activation, differentiation, and fusion of satellite cells. Satellite cells composing an individual muscle are heterogeneous, which will differentially affect muscle growth. The proliferation and differentiation of turkey primary pectoralis major muscle cells were investigated in vitro at 1 d of age and at 4, 8, 16, 26, 35, 45, and 54 wk of age. The turkey was selected for these studies because turkey skeletal muscle fibroblasts do not grow in primary muscle cell cultures. Results from the proliferation analysis showed a decrease in proliferation by 8 wk of age. Differentiation into myotubes was significantly decreased by 4 wk of age and myotube diameter was decreased. The changes in muscle weight relative to total BW were measured for the anterior latissimus dorsi, biceps brachii, pectoralis major, sartorius, biceps femoris, and gastrocnemius muscles to compare the relative growth of different muscles. The age at which the muscles reached their maximum relative weight was muscle-dependent, with the biceps brachii plateauing the earliest at 4 wk and the sartorius the latest at 45 wk of age. These data suggested that changes in myogenic cells begin to occur early in muscle development and the activity of the satellite cells during these initial stages of posthatch growth is critical in overall muscle mass accumulation. PMID- 20308403 TI - Early feeding affects resistance against cold exposure in young broiler chickens. AB - In field conditions, a fasting period of 24 to 72 h after hatch is common, which is associated with delayed gastrointestinal development and yolk utilization and retarded subsequent performance. Hardly any information is available about the influence of diet composition in the first days on later life and additionally, effects of early feeding on thermoregulatory development are also not known. The aim of this study was to investigate effects of diet composition in early fed broiler chickens on their (thermoregulatory) development. Shortly after hatch, 200 Hybro chickens (initial BW of 43.6 g) were assigned to 1 of 5 feed treatments: control, dextrose, albumen, prestarter, or prestarter plus fat. Water was available ad libitum. Measurements were done in 10 replicates of 4 chickens per treatment. At d 2 or 3, half of the chickens were exposed to 20 degrees C for 30 min to determine resistance against cold exposure and rectal temperature was determined just before, immediately after, and 30 min after the end of this cold exposure. Thereafter, all chickens were killed to investigate body development. Chickens in both prestarter groups developed faster than in the other 3 groups, expressed by a higher BW, yolk-free body mass, heart and liver weight, and higher chick and intestine length. Between d 2 and 3, differences in these variables among chickens from both prestarter groups and other groups increased. Rectal temperature before cold exposure was higher in chickens from both prestarter groups (40.6 and 40.7 degrees C, respectively) and decreased less (0.6 and 0.7 degrees C, respectively) during cold exposure than in chickens from the control (39.5 and 1.2 degrees C, respectively) and albumen group (39.8 and 2.1 degrees C, respectively), whereas chickens from the dextrose group were in between (40.4 and 1.2 degrees C, respectively). We conclude that early fed diet composition in broiler chickens is (besides general development) important for development of both body temperature and resistance against cold exposure, probably as a reflection of a changed metabolic rate. PMID- 20308405 TI - Changes in physicochemical properties of egg white and yolk proteins from duck shell eggs due to hydrostatic pressure treatment. AB - The shell of the duck egg did not crack after pressure treatments (300 to 500 MPa; 25 degrees C; 10 min) in this study; therefore, the changes of physicochemical properties of egg white and yolk proteins from the intact shell egg by pressure treatment were first investigated and compared with those of pressurized hen liquid eggs. Although the proximate compositions of duck eggs and hen eggs were similar, the moisture and protein contents of hen whole eggs were higher than those of duck whole eggs. The protein contents of duck egg white and yolk were slightly lower than those of hen eggs, and the moisture content of duck egg white was equal to that of hen egg white, whereas that of duck egg yolk was lower than that of hen egg yolk. After pressure treatment at 500 MPa, the results of solubility, sulfhydryl content, surface hydrophobicity, and residual denaturation enthalpy showed that egg white proteins underwent slight but significant unfolding and aggregation, whereas pressure treatments below 500 MPa induced insignificant changes in the physicochemical properties. On the other hand, pressure treatments at 400 and 500 MPa significantly reduced the solubility and residual denaturation enthalpy of egg yolk proteins. However, the native PAGE result showed that pressure treatment up to 500 MPa did not affect the protein components of egg white and yolk. The results showed that the application of pressure treatment on duck shell egg may induce reversible denaturation of both egg white and yolk proteins. The egg white and yolk proteins may be prevented from denaturation after pressure treatment in the presence of the eggshell compared with the absence of the eggshell. As reported in the literature, pressure treatments at 300 to 500 MPa and 25 degrees C would be efficient for decontamination of duck shell eggs. Therefore, based on the consideration for food safety and functional properties, pressure processing can be a good preservation technique for duck shell eggs. PMID- 20308404 TI - Soybean, palm kernel, and animal-vegetable oils and vitamin E supplementation effect on lipid oxidation stability of sous vide chicken meat. AB - There is an increasing demand in precooked chicken meat products for restaurants and catering services. Because cooked chicken meat develops lipid oxidation relatively fast, sous vide chicken meat was studied to assess its shelf-life. Six hundred Cobb x Ross broilers were fed for 6 wk with a basal corn-soybean meal diet including soybean, palm kernel, or animal-vegetable oil, each supplemented with 33 or 200 mg/kg of dl-alpha-tocopheryl acetate. Broilers were randomly assigned into 6 treatments and 4 repetitions with 25 birds each. Boneless breast or thigh muscle pieces were dissected into 5 x 5 x 5 cm cubes, vacuum-packed, cooked in water bath (until 74 degrees C internal temperature), chilled, and stored at 4 degrees C for 1, 5, 10, 25, and 40 d. For each storage day, each pouch contained 3 pieces of meat, either breast or thigh. Thiobarbituric acid reactive substances analysis, to quantify malonaldehyde (MDA) values, was conducted to estimate the lipid oxidation development. Nonheme iron values of cooked meat were analyzed. Fatty acid methyl esters analysis was performed in chicken muscle to determine its fatty acid composition. There was no interaction between dietary fat and vitamin E level in all of the variables studied except in nonheme iron. Dietary fat significantly influenced the fatty acid composition of the muscle (P < 0.01), but it did not affect the MDA values, regardless of differences in the muscle fatty acid composition between treatments. Supplementation of the high level of vitamin E significantly reduced the MDA values in both breast and thigh meat (P < 0.01). The maximum MDA values were observed at d 40 of storage in thigh and breast meat in animal-vegetable and soybean oil treatments with the low levels of vitamin E, 0.91 and 0.70 mg/kg, respectively. Nonheme iron values in thigh meat differed between treatments at 1 or 25 d of storage but not in breast meat. In conclusion, refrigerated sous vide chicken meat has a prolonged shelf-life, which is enhanced by dietary supranutritional supplementation of vitamin E. PMID- 20308406 TI - Oil exudation and histological structures of duck egg yolks during brining. AB - Changes in oil exudation and histological structures of salted duck egg yolks during brining up to 5 wk were investigated. During brining, the salt contents of albumen, exterior yolk (hardened portion), and interior yolk (soft or liquid portion) gradually increased accompanied by slight decreases in moisture content. The hardening ratio of salted egg yolks increased rapidly to about 60% during the first week of brining and then reached 100% at the end of brining. After brining, part of the lipids in salted egg yolk became free due to the structural changes of low-density lipoprotein induced by dehydration and increase of salt content, and more free lipids in salted egg yolk were released after the cooking process. With the brining time increased up to 5 wk, the outer region of the cooked salted yolk gradually changed into dark brown, brown, orange, and then dark brown, whereas the center region changed into light yellow, yellow, dark yellow, and then yellow again. The microstructures of cooked salted egg yolks showed that the yolk spheres in the outer and middle regions retained their original shape, with some shrinking and being packed more loosely when brining time increased, and the exuded oil filled the space between the spheres. Furthermore, the yolk spheres in the center region transformed to a round shape but still showed granulation after 4 wk of brining, whereas they were mostly disrupted after 2 to 5 wk of brining. One of the most important characteristics of cooked salted egg yolks, gritty texture, contributed to oil exudation and granulated yolk spheres were observed at the brining time of 4 wk. PMID- 20308407 TI - Effects on egg quality traits of genotype and diets with mussel meal or wheat distillers dried grains with solubles. AB - The aim of the study was to evaluate effects on exterior and interior egg quality and sensory characteristics of eggs from hens fed diets with admixtures of 3.5 or 7.0% of mussel meal or 20% wheat-distillers dried grains with solubles (DDGS). The mussel meal diets followed organic standards, whereas the DDGS diet was formulated for hens in conventional production. Standard diets, one organic and one conventional from a Swedish feed manufacturer, were included for comparison. The study used 164 Hy-Line White W-98 and 164 Hy-Line Brown layers housed in small-group furnished cages. Egg flavor or odor was not affected by genotype. Egg flavor intensity was stronger in eggs from hens fed either of the mussel diets or the standard organic diet compared with the conventional diet. There were no differences between any of the diets in egg odor intensity, off-flavor, or off odor. The mussel diets and the standard organic diet gave stronger yolk pigmentation than the conventional and DDGS diet, respectively. Manure DM was lower with the admixture of 7.0% mussel meal than 3.5%. There was a tendency (P < 0.10) toward a difference between diets in dirty eggs, and the percentage was highest with 7.0% mussel meal. Diet or genotype had no effect on egg weight, albumen height, shell deformation, shell breaking strength, or proportion of cracked eggs. Genotype differences were found in weight percentage of albumen, yolk, and shell and in the presence of blood and meat spots and in percentage of dirty eggs. In conclusion, the majority of egg quality traits were unaffected by the diets studied. With the admixture of DDGS used in the present study, the characteristics of eggs were similar to those of eggs produced on the conventional standard diet. There was no indication of impaired egg odor or flavor with the used fractions of DDGS or mussel meal. PMID- 20308408 TI - Dietary inclusion level effects of distillers dried grains with solubles on broiler meat quality. AB - A completely randomized design with 7 replications (n = 7, treatments = 5 with 8 subsamples per treatment) was used to evaluate the effects of feeding various levels of distillers dried grains with solubles (DDGS; 0, 6, 12, 18, and 24%) on broiler breast and thigh meat quality. Broilers were harvested in a pilot scale processing plant with commercial prototype equipment at 42 d of age. The right half of each breast was evaluated for pH, instrumental color, cooking loss, proximate analysis, and tenderness. The left half of each breast was used for consumer acceptability testing. Thigh meat was evaluated for proximate composition, fatty acid composition, and TBA reactive substances. Breast meat from broilers that were fed DDGS had a higher (P < 0.05) pH than those from the control diet. In addition, the 18 and 24% DDGS treatments yielded breast meat with higher (P < 0.05) pH values than the 6% DDGS treatment. No differences existed (P > 0.05) among breast meat from the different treatments with respect to cooking loss, instrumental color, and consumer acceptability, but breast meat from the control (0% DDGS) treatment had slightly lower (P < 0.05) shear force than breast meat from the 18 and 24% DDGS treatments. In addition, no differences (P > 0.05) existed among proximate composition of breast and thigh meat from the control and DDGS treatments. As DDGS concentration increased, there was a linear increase (P < 0.05) in linoleic and polyunsaturated fatty acids, which indicates a greater potential for lipid oxidation. The TBA reactive substances values were greater (P < 0.05) for the 18 and 24% DDGS treatments at d 5 when compared with the control and 6% DDGS treatments, which indicates increased oxidation. Overall, data suggest that all treatments yielded high-quality breast meat and that thigh meat quality was similar among treatments containing 0 to 12% DDGS, but higher inclusion levels led to thigh meat that was more susceptible to oxidation. PMID- 20308409 TI - Modified pressure imaging for egg crack detection and resulting egg quality. AB - Cracks in the shell surface compromise the primary barrier for external microbial contamination of the egg. Microcracks are very small cracks in the shell surface that are difficult to detect by human graders. New technology has been developed that uses modified pressure and imaging to detect microcracks in eggs. Research has shown the system to have an accuracy of 99.6% in detecting both cracked and intact eggs. A study was undertaken to determine if quality differences existed between modified pressure imaged and control eggs during extended cold storage. Three replicates were conducted with eggs stored at 4 degrees C for 5 wk with weekly quality testing. The physical quality factors monitored were Haugh units, albumen height, egg weight, shell strength, vitelline membrane strength and elasticity, and whole egg total solids. All measurements were conducted on individual eggs (12/treatments per replicate) each week with the exception of whole egg solids, which were determined from 3 pools (4 eggs each)/treatment per replicate each week. Percentage of whole egg total solids was the only significant difference (P < 0.05) between treatments (23.65% modified pressure imaged and 23.47% control). There was a significant difference (P < 0.05) for egg weight between replicates (60.82, 58.02, and 60.58 g for replicates 1, 2, and 3, respectively). Therefore, imaging eggs in the modified pressure system for microcrack detection did not alter egg quality during extended cold storage. Utilizing the modified pressure crack detection technology would result in fewer cracked eggs reaching the consumer, consequently enhancing food safety without affecting product quality. PMID- 20308410 TI - Alkali-aided protein extraction of chicken dark meat: composition and stability to lipid oxidation of the recovered proteins. AB - Chicken dark meat has been considered as a major underused commodity due to the increasing demand for further-processed breast meat products. One option to increase the utilization of chicken dark meat is to extract myofibrillar proteins and separate them from fat and pigments to enhance their application for the preparation of further-processed meat products. The objective of the current study was to determine the effect of pH, in the range of 10.5 to 12.0, on the alkaline solubilization process of chicken dark meat. Aspects studied were the effect of the alkali-aided process on protein content, lipid composition, lipid oxidation, and color characteristics of the extracted meat. Each experiment and each assay were done at least in triplicate. Lipid content of the extracted meat showed a 50% reduction compared with the chicken dark meat. Neutral lipids were reduced by 61.51%, whereas polar lipids were not affected by the alkali treatments. There was a higher amount of TBA reactive substances observed in the extracted meat compared with chicken dark meat, indicating that extracted meat was more susceptible to oxidation. Long-chain polyunsaturated fatty acids (22:4n 6, 20:3n-3, 20:5n-3, 22:5n-3, and 22:6n-3), which were detected only in the polar lipids, were responsible for increasing lipid oxidation susceptibility of extracted meat compared with chicken dark meat. Alkali-aided extraction of chicken dark meat lightened the color of the meat. The redness, yellowness, and total heme pigments in extracted meat significantly decreased by 83, 11, and 53%, respectively, compared with chicken dark meat. Even though this process did not remove polar lipids, based on our early findings, the extracted meat had considerable physicochemical and textural properties for product preparation compared with those of raw dark meat. Hence, alkali recovery of protein can be considered a potentially useful method to increase the utilization of dark chicken meat. PMID- 20308411 TI - Computational study of the heat transfer of an avian egg in a tray. AB - The development of an embryo in an avian egg depends largely on its temperature. The embryo temperature is affected by its environment and the heat produced by the egg. In this paper, eggshell temperature and the heat transfer characteristics from one egg in a tray toward its environment are studied by means of computational fluid dynamics (CFD). Computational fluid dynamics simulations have the advantage of providing extensive 3-dimensional information on velocity and eggshell temperature distribution around an egg that otherwise is not possible to obtain by experiments. However, CFD results need to be validated against experimental data. The objectives were (1) to find out whether CFD can successfully simulate eggshell temperature from one egg in a tray by comparing to previously conducted experiments, (2) to visualize air flow and air temperature distribution around the egg in a detailed way, and (3) to perform sensitivity analysis on several variables affecting heat transfer. To this end, a CFD model was validated using 2 sets of temperature measurements yielding an effective model. From these simulations, it can be concluded that CFD can effectively be used to analyze heat transfer characteristics and eggshell temperature distribution around an egg. In addition, air flow and temperature distribution around the egg are visualized. It has been observed that temperature differences up to 2.6 degrees C are possible at high heat production (285 mW) and horizontal low flow rates (0.5 m/s). Sensitivity analysis indicates that average eggshell temperature is mainly affected by the inlet air velocity and temperature, flow direction, and the metabolic heat of the embryo and less by the thermal conductivity and emissivity of the egg and thermal emissivity of the tray. PMID- 20308412 TI - Sequential feeding using whole wheat and a separate protein-mineral concentrate improved feed efficiency in laying hens. AB - The effect of feeding nutritionally different diets in sequential or loose-mix systems on the performance of laying hen was investigated from 16 to 46 wk of age. Equal proportions of whole wheat grain and protein-mineral concentrate (balancer diet) were fed either alternatively (sequential) or together (loose mix) to ISA Brown hens. The control was fed a complete layer diet conventionally. Each treatment was allocated 16 cages and each cage contained 5 birds. Light was provided 16 h daily (0400 to 2000 h). Feed offered was controlled (121 g/bird per d) and distributed twice (4 and 11 h after lights-on). In the sequential treatment, only wheat was fed at first distribution, followed by balancer diet at the second distribution. In loose-mix, the 2 rations were mixed and fed together during the 2 distributions. Leftover feed was always removed before the next distribution. Sequential feeding reduced total feed intake when compared with loose-mix and control. It had lower wheat (-9 g/bird per d) but higher balancer (+1.7 g/bird per d) intakes than loose-mix. Egg production, egg mass, and egg weight were similar among treatments. This led to an improvement in efficiency of feed utilization in sequential compared with loose-mix and control (10 and 5%, respectively). Birds fed sequentially had lower calculated ME (kcal/bird per d) intake than those fed in loose-mix and control. Calculated CP (g/bird per d) intake was reduced in sequential compared with loose-mix and control. Sequentially fed hens were lighter in BW. However, they had heavier gizzard, pancreas, and liver. Similar liver lipid was observed among treatments. Liver glycogen was higher in loose-mix than the 2 other treatments. It was concluded that feeding whole wheat and balancer diet, sequentially or loosely mixed, had no negative effect on performance in laying hens. Thus, the 2 systems are alternative to conventional feeding. The increased efficiency of feed utilization in sequential feeding is an added advantage compared with loose-mix and thus could be employed in situations where it is practicable. PMID- 20308413 TI - Food, energy, and the environment. AB - During the 2009 annual meeting of the Poultry Science Association, a symposium entitled "Global Views of New Agriculture: Food, Energy, and the Environment" was held that focused on several major issues affecting agriculture. Issues included future funding for basic agricultural research, sustainability, bioenergy, and their effects on global food markets. In many ways, a subtitle for the symposium could have been "Agriculture-Why What We Do Matters." It matters because of the fiscal and physical realities the planet will face in the coming decades relative to human population growth and the increasing demands to feed a hungry world. The challenges are daunting and the technologies to address them will require us to reevaluate the structure and policies we have established relative to agricultural research. In this case, change is all the more difficult because the traditional model of agricultural research has been so successful. One only needs to note the remarkable increases in productivity of the past half century of commodities such as corn and soybeans or feed efficiencies among broilers, laying hens, and turkeys to recognize the significant advancements that have been achieved. However, these historic gains have frequently required increased inputs, most notably fossil fuels. Food production in the future will likely be confronted with concerns involving energy, water, climate change, and the threat of agroterrorism. For example, we will need to develop crops that are more drought-resistant and more tolerant to a wider range of salinities as access to fresh water becomes more problematic. Animal agriculture will also need to adapt to diets composed of atypical feedstuffs. Whether future generations will inherit a world described by Paul Roberts in his books The End of Oil and The End of Food will be in part determined by the research model we adopt in the near term. PMID- 20308415 TI - Breeding of tomorrow's chickens to improve well-being. AB - Chickens, as well as other animals, have the ability to change their behavior (behavioral plasticity) and physiology (physiological plasticity) based on the costs and benefits to fit their environment (adaptation). Through natural selection, the population preserves and accumulates traits that are beneficial and rejects those that are detrimental in their prevailing environments. The surviving populations are able to contribute more genes associated with beneficial traits for increased fitness to subsequent generations. Natural selection is slow but constant; working over multiple generations, the changes to the population often appear silent or undetectable at a given point in history. Chickens were domesticated from the wild red jungle fowl. The principle of domestication of chickens, as well as other farm animals, by humans is similar to that of natural selection: selecting the best animals with the highest survivability and reproducibility (artificial selection). Compared with natural selection, the process of artificial selection is motivated by human needs and acts more rapidly with more visible results over a short time period. This process has been further accelerated following the development of current breeding programs and the emergence of specialized breeding companies. A laying hen, for example, produces more than 300 hundred eggs a year, whereas a jungle fowl lays 4 to 6 eggs in a year. During the domestication process, chickens retained their capability to adapt to their housing environments, which is usually achieved by genetic changes occurring with each subsequent generation. Genes control the behavioral, physiological, immunological, and psychological responses of animals to stressors, including environmental stimulations. With advances in understanding of genetic mediation of animal physiology and behavior and the discovery of the genome sequences of many species, animal production breeding programs can be improved in both speed and efficiency. Modern chicken breeding programs have the potential to be operated successfully in the breeding of tomorrow's chickens with high production efficiency and optimal welfare, resulting from resistance to stress, disease, or both. PMID- 20308416 TI - Why using genetics to address welfare may not be a good idea. AB - Welfare of animals in livestock production systems is now widely defined in terms of 3 classes of measures: veterinary health, mental well-being (or feelings), and natural behaviors. Several well-documented points of tension exist among welfare indicators in these 3 classes. Strategies that aim to improve welfare using genetics can increase resistance to disease and may also be able to relieve stress or injury. One strategy is to reduce the genetic proclivity of the bird to engage in behaviors that are frustrated in modern production systems. Another is to develop strains less prone to behaviors hurtful to other hens. Yet another is to make overall temperament a goal for genetic adjustments. These genetic approaches may score well in terms of veterinary and psychological well-being. Yet they also involve changes in behavioral repertoire and tendencies of the resulting bird. Although it has seemed reasonable to argue that such animals are better off than frustrated or injured animals reflecting more species-typical behaviors, there is a point of view that holds that modification of a species typical trait is ipso facto a decline in the well-being of the animal. Additionally, a significant amount of anecdotal evidence has been accumulated that suggests that many animal advocates and members of the public find manipulation of genetics to be an ethically unacceptable approach to animal welfare, especially when modifications in the environment could also be a response to welfare problems. Hence, though promising from one perspective, genetic strategies to improve welfare may not be acceptable to the public. PMID- 20308417 TI - Primary broiler breeding--striking a balance between economic and well-being traits. AB - Primary breeders are well aware that selecting for better health and well-being along with economic traits such as faster growth rate, higher levels of meat yield, and improved efficiency of feed utilization are critical to balanced long term genetic progress of their pure lines as well as to increased production efficiency of broiler products for the broiler industry. Cobb collects and selects on over 50 phenotypic observations per pedigree candidate at various ages. Over 50% of these collections are involved with evaluation of each bird's health, welfare, and fitness. Some examples of these traits are various chick defects, various broiler age skeletal and leg abnormalities, feather cover, various physiological measures of heart and lung functions, and specific causes of mortality. Large pedigree populations, massive data collection infrastructure, integration of better technologies in evaluation of phenotypes, and sophisticated data analysis capability have allowed geneticists to perform selections that are balanced for both economic and welfare traits. Cobb's internal as well as worldwide sponsored research has facilitated geneticists to make science-based breeding decisions. Each pedigree line per product available to primary breeders exhibits their own unique characteristics that are enhanced by selective breeding and positioned in special mating schemes to produce the product and welfare performance that our customers demand. Additionally, most if not all primary breeding companies now offer different products for different markets that exhibit varying levels of performance and behavior to fit customer needs. Future expansion of these products and creation of new products by breeding companies will be in large dictated by both our customers and consumers. PMID- 20308418 TI - The European experience in poultry welfare--a decade ahead. AB - Farm animal welfare is a major issue in Europe, which resulted in regulations and development of research dedicated to animal welfare, especially on standard poultry production, which is often considered as resulting in very poor welfare. The effect of selection is also often questioned. Indeed, capacities of adaptation have been very little considered during the first years of commercial selection and thus have been reduced. Nowadays, a much greater importance is given to welfare-related traits and genomic selection should alleviate the need for their measurements in the short-term. However, the choice of the fittest selection criteria is still to be made. Because behavioral traits are highly dependent on environment, general reactivity may be more efficient. For example, selection against undesirable behavior such as feather pecking has been proven to be efficient, but selection for reduced mortality rates in collective cages proved to be preferable. Most often, selection should not exacerbate extreme values, which are most often detrimental, as in the case of social motivation, which, when increased to too large of an extent, results in increased aggressivity. Moreover, a general propensity will not result in overall improvement; for example, reducing fearfulness has positive effects but does not modify response to social stress. Detrimental effects on other traits may also be observed: although genetic resistance to diseases should increase animal welfare, it may also result in increased frequency of silent carriers and in turn to human transmission. Indeed, an optimum must be found. Studying lines selected for or against these traits will be of great help to choose the best strategy of selection. Another and longer term concern should be on links with other production traits but also on sustainability, which will probably be of greater importance in the coming years. PMID- 20308419 TI - Molecular neuroendocrine events during stress in poultry. AB - Magnocellular neurons in the hypothalamic paraventricular nucleus containing arginine vasotocin (AVT) project to the posterior pituitary and release the peptide peripherally to target tissues. Parvocellular neurons contain either corticotropin-releasing hormone (CRH), AVT, or both neuropeptides and project to the median eminence. Corticotropin-releasing hormone and AVT are then transported to the anterior pituitary where they bind to CRH1 or vasotocin VT2 receptors, many found co-localized on the same pituitary cell type, the corticotrope. Central administration of CRH compared with AVT is more effective in releasing the stress hormone corticosterone, whereas peripheral administration of AVT is more efficacious. Simultaneous, peripheral administration of CRH and AVT also resulted in a synergistic release of corticosterone. Cell culture studies demonstrated a synergistic release of the second messenger, cyclic adenosine monophosphate, when both CRH and AVT were added to cells transfected with CRH and VT2 receptors, providing a possible explanation for the enhanced release of corticosterone following combined peripheral administration of the 2 peptides. A social stress model, mature male-male interaction, demonstrated activation of neurons in the paraventricular nucleus and suggested that the posterior pituitary as well as the anterior pituitary are involved in a social stress response. PMID- 20308420 TI - Understanding stress-induced immunosuppression: exploration of cytokine and chemokine gene profiles in chicken peripheral leukocytes. AB - At present, the poultry meat and egg industry has gained a lot of ground, being viewed as a provider of a healthy alternative to red meat and other protein sources. If this trend is to be maintained, solutions must be found to improve resistance of chickens to disease, which often is weakened by stressful conditions. In poultry, stress-induced immunosuppression is manifested by failures in vaccination and increased morbidity and mortality of flocks. Currently, several modern cellular and molecular approaches are being used to explore the status of the immune system during stress and disease. It is likely that these new techniques will lead to the development of new strategies for preventing and controlling immunosuppression in poultry. Using quantitative reverse transcription-PCR assays, a broad spectrum of cytokine, chemokine, and their receptor genes can be quantified in birds and then be used as markers to assess the effects of stress on the immune system. Currently, we are investigating immune and endocrine interactions in the chicken, in particular the cells and molecules that are known to be involved in such interactions in mammals. We have evaluated the effects of corticosterone administration in drinking water on peripheral lymphocyte and heterophil cytokine and chemokine gene profiles. In particular, there seems to be effects on cytokine and chemokine mRNA expression levels in both lymphocytes and heterophils, especially expression of the proinflammatory cytokines interleukin (IL)-1beta, IL-6, and IL-18 and chemokines C-C motif, ligand 1 inflammatory (CCLi1); C-C motif, ligand 2 inflammatory (CCLi2); C-C motif, ligand 5 (CCL5); C-C motif, ligand 16 (CCL16); C X-C motif ligand 1 inflammatory (CXCLi1); and C-X-C motif ligand 2 inflammatory (CXCLi2), which are initially upregulated and are potentially involved in modulating the adaptive immune response. A chronic treatment with corticosterone downregulates proinflammatory cytokines and chemokines, suggesting that the delayed effects of chronic stress can suppress the immune response. Messenger RNA expression levels of transforming growth factor-beta4 (TGF-beta4) are also upregulated in cortisosterone-treated birds. It appears that the balance between T-helper (Th) 1 and Th2/T regulatory cytokine production is altered in conditions associated with significant changes in plasma corticosterone concentration. Experiments are underway to decipher the cytokine and chemokine responses to vaccination and bacterial challenge on the background of stress-induced immunosuppression. PMID- 20308421 TI - Modification of animals versus modification of the production environment to meet welfare needs. AB - The balance between genetic modification and welfare may be as old as the chicken and egg debate. Meeting welfare needs of farm animals has become an integral part of animal agriculture. Until recently, environmental and management modifications have been the methods of choice for meeting welfare needs of animals. Genetic selection has improved growth, livability, and general welfare, but some aspects of welfare like metabolic disorders, susceptibility to some diseases, and skeletal problems have increased. Genetic variability in behavioral and physiological traits relating to welfare exists thus raising the possibility of selecting for welfare-related traits. Advances in molecular biology have also made it possible for the identification of QTL for behavioral and welfare traits. Identification of causal or associative genes for welfare traits and improved biotechnology tools raises the possibility of either selecting for improved welfare or genetically modifying birds to suit the commercial production environment. An integration of management, genetics, and genomic tools should be employed to genetically improve production and welfare traits with concurrent welfare risk assessments to address public and consumer concerns. PMID- 20308422 TI - Doug Hilton: at home with blood cell biology. Interview by Caitlin Sedwick. PMID- 20308423 TI - New insights into oxidative folding. AB - The oxidoreductase ERO1 (endoplasmic reticulum [ER] oxidoreductin 1) is thought to be crucial for disulfide bond formation in the ER. In this issue, Zito et al. (2010. J. Cell Biol. doi:10.1083/jcb.200911086) examine the division of labor between the two mammalian isoforms of ERO1 (ERO1-alpha and -beta) in oxidative folding. Their analysis reveals a selective role for ERO1-beta in insulin production and a surprisingly minor contribution for either ERO1 isoform on immunoglobulin folding and secretion. PMID- 20308424 TI - Mammalian BLM helicase is critical for integrating multiple pathways of meiotic recombination. AB - Bloom's syndrome (BS) is an autosomal recessive disorder characterized by growth retardation, cancer predisposition, and sterility. BS mutated (Blm), the gene mutated in BS patients, is one of five mammalian RecQ helicases. Although BLM has been shown to promote genome stability by assisting in the repair of DNA structures that arise during homologous recombination in somatic cells, less is known about its role in meiotic recombination primarily because of the embryonic lethality associated with Blm deletion. However, the localization of BLM protein on meiotic chromosomes together with evidence from yeast and other organisms implicates a role for BLM helicase in meiotic recombination events, prompting us to explore the meiotic phenotype of mice bearing a conditional mutant allele of Blm. In this study, we show that BLM deficiency does not affect entry into prophase I but causes severe defects in meiotic progression. This is exemplified by improper pairing and synapsis of homologous chromosomes and altered processing of recombination intermediates, resulting in increased chiasmata. Our data provide the first analysis of BLM function in mammalian meiosis and strongly argue that BLM is involved in proper pairing, synapsis, and segregation of homologous chromosomes; however, it is dispensable for the accumulation of recombination intermediates. PMID- 20308425 TI - ERO1-beta, a pancreas-specific disulfide oxidase, promotes insulin biogenesis and glucose homeostasis. AB - Mammals have two genes encoding homologues of the endoplasmic reticulum (ER) disulfide oxidase ERO1 (ER oxidoreductin 1). ERO1-beta is greatly enriched in the endocrine pancreas. We report in this study that homozygosity for a disrupting allele of Ero1lb selectively compromises oxidative folding of proinsulin and promotes glucose intolerance in mutant mice. Surprisingly, concomitant disruption of Ero1l, encoding the other ERO1 isoform, ERO1-alpha, does not exacerbate the ERO1-beta deficiency phenotype. Although immunoglobulin-producing cells normally express both isoforms of ERO1, disulfide bond formation and immunoglobulin secretion proceed at nearly normal pace in the double mutant. Moreover, although the more reducing environment of their ER protects cultured ERO1-beta knockdown Min6 cells from the toxicity of a misfolding-prone mutant Ins2(Akita), the diabetic phenotype and islet destruction promoted by Ins2(Akita) are enhanced in ERO1-beta compound mutant mice. These findings point to an unexpectedly selective function for ERO1-beta in oxidative protein folding in insulin-producing cells that is required for glucose homeostasis in vivo. PMID- 20308426 TI - The TWEAK-Fn14 system is a critical regulator of denervation-induced skeletal muscle atrophy in mice. AB - Skeletal muscle atrophy occurs in a variety of clinical settings, including cachexia, disuse, and denervation. Inflammatory cytokines have been shown to be mediators of cancer cachexia; however, the role of cytokines in denervation- and immobilization-induced skeletal muscle loss remains unknown. In this study, we demonstrate that a single cytokine, TNF-like weak inducer of apoptosis (TWEAK), mediates skeletal muscle atrophy that occurs under denervation conditions. Transgenic expression of TWEAK induces atrophy, fibrosis, fiber-type switching, and the degradation of muscle proteins. Importantly, genetic ablation of TWEAK decreases the loss of muscle proteins and spared fiber cross-sectional area, muscle mass, and strength after denervation. Expression of the TWEAK receptor Fn14 (fibroblast growth factor-inducible receptor 14) and not the cytokine is significantly increased in muscle upon denervation, demonstrating an unexpected inside-out signaling pathway; the receptor up-regulation allows for TWEAK activation of nuclear factor kappaB, causing an increase in the expression of the E3 ubiquitin ligase MuRF1. This study reveals a novel mediator of skeletal muscle atrophy and indicates that the TWEAK-Fn14 system is an important target for preventing skeletal muscle wasting. PMID- 20308427 TI - Endogenous Bak inhibitors Mcl-1 and Bcl-xL: differential impact on TRAIL resistance in Bax-deficient carcinoma. AB - Tumor necrosis factor (alpha)-related apoptosis-inducing ligand (TRAIL) is a promising anticancer agent that preferentially kills tumor cells with limited cytotoxicity to nonmalignant cells. However, signaling from death receptors requires amplification via the mitochondrial apoptosis pathway (type II) in the majority of tumor cells. Thus, TRAIL-induced cell death entirely depends on the proapoptotic Bcl-2 family member Bax, which is often lost as a result of epigenetic inactivation or mutations. Consequently, Bax deficiency confers resistance against TRAIL-induced apoptosis. Despite expression of Bak, Bax deficient cells are resistant to TRAIL-induced apoptosis. In this study, we show that the Bax dependency of TRAIL-induced apoptosis is determined by Mcl-1 but not Bcl-xL. Both are antiapoptotic Bcl-2 family proteins that keep Bak in check. Nevertheless, knockdown of Mcl-1 but not Bcl-xL overcame resistance to TRAIL, CD95/FasL and tumor necrosis factor (alpha) death receptor ligation in Bax deficient cells, and enabled TRAIL to activate Bak, indicating that Mcl-1 rather than Bcl-xL is a major target for sensitization of Bax-deficient tumors for death receptor-induced apoptosis via the Bak pathway. PMID- 20308428 TI - The PI3K p110alpha isoform regulates endothelial adherens junctions via Pyk2 and Rac1. AB - Endothelial cell-cell junctions control efflux of small molecules and leukocyte transendothelial migration (TEM) between blood and tissues. Inhibitors of phosphoinositide 3-kinases (PI3Ks) increase endothelial barrier function, but the roles of different PI3K isoforms have not been addressed. In this study, we determine the contribution of each of the four class I PI3K isoforms (p110alpha, beta, -gamma, and -delta) to endothelial permeability and leukocyte TEM. We find that depletion of p110alpha but not other p110 isoforms decreases TNF-induced endothelial permeability, Tyr phosphorylation of the adherens junction protein vascular endothelial cadherin (VE-cadherin), and leukocyte TEM. p110alpha selectively mediates activation of the Tyr kinase Pyk2 and GTPase Rac1 to regulate barrier function. Additionally, p110alpha mediates the association of VE cadherin with Pyk2, the Rac guanine nucleotide exchange factor Tiam-1 and the p85 regulatory subunit of PI3K. We propose that p110alpha regulates endothelial barrier function by inducing the formation of a VE-cadherin-associated protein complex that coordinates changes to adherens junctions with the actin cytoskeleton. PMID- 20308429 TI - Myosin II activity regulates vinculin recruitment to focal adhesions through FAK mediated paxillin phosphorylation. AB - Focal adhesions (FAs) are mechanosensitive adhesion and signaling complexes that grow and change composition in response to myosin II-mediated cytoskeletal tension in a process known as FA maturation. To understand tension-mediated FA maturation, we sought to identify proteins that are recruited to FAs in a myosin II-dependent manner and to examine the mechanism for their myosin II-sensitive FA association. We find that FA recruitment of both the cytoskeletal adapter protein vinculin and the tyrosine kinase FA kinase (FAK) are myosin II and extracellular matrix (ECM) stiffness dependent. Myosin II activity promotes FAK/Src-mediated phosphorylation of paxillin on tyrosines 31 and 118 and vinculin association with paxillin. We show that phosphomimic mutations of paxillin can specifically induce the recruitment of vinculin to adhesions independent of myosin II activity. These results reveal an important role for paxillin in adhesion mechanosensing via myosin II-mediated FAK phosphorylation of paxillin that promotes vinculin FA recruitment to reinforce the cytoskeletal ECM linkage and drive FA maturation. PMID- 20308430 TI - The Arf tumor suppressor protein inhibits Miz1 to suppress cell adhesion and induce apoptosis. AB - Oncogenic stress induces expression of the alternate reading frame (Arf) tumor suppressor protein. Arf then stabilizes p53, which leads to cell cycle arrest or apoptosis. The mechanisms that distinguish both outcomes are incompletely understood. In this study, we show that Arf interacts with the Myc-associated zinc finger protein Miz1. Binding of Arf disrupts the interaction of Miz1 with its coactivator, nucleophosmin, induces the sumoylation of Miz1, and facilitates the assembly of a heterochromatic complex that contains Myc and trimethylated H3K9 in addition to Miz1. Arf-dependent assembly of this complex leads to the repression of multiple genes involved in cell adhesion and signal transduction and induces apoptosis. Our data point to a tumor-suppressive pathway that weakens cell-cell and cell-matrix interactions in response to expression of Arf and that may thereby facilitate the elimination of cells harboring an oncogenic mutation. PMID- 20308431 TI - Fibroblast growth factor receptors 1 and 2 in keratinocytes control the epidermal barrier and cutaneous homeostasis. AB - Fibroblast growth factors (FGFs) are master regulators of organogenesis and tissue homeostasis. In this study, we used different combinations of FGF receptor (FGFR)-deficient mice to unravel their functions in the skin. Loss of the IIIb splice variants of FGFR1 and FGFR2 in keratinocytes caused progressive loss of skin appendages, cutaneous inflammation, keratinocyte hyperproliferation, and acanthosis. We identified loss of FGF-induced expression of tight junction components with subsequent deficits in epidermal barrier function as the mechanism underlying the progressive inflammatory skin disease. The defective barrier causes activation of keratinocytes and epidermal gammadelta T cells, which produce interleukin-1 family member 8 and S100A8/A9 proteins. These cytokines initiate an inflammatory response and induce a double paracrine loop through production of keratinocyte mitogens by dermal cells. Our results identify essential roles for FGFs in the regulation of the epidermal barrier and in the prevention of cutaneous inflammation, and highlight the importance of stromal epithelial interactions in skin homeostasis and disease. PMID- 20308432 TI - Association analysis of 33 lipoprotein candidate genes in multi-generational families of African ancestry. AB - African ancestry individuals have a more favorable lipoprotein profile than Caucasians, although the mechanisms for these differences remain unclear. We measured fasting serum lipoproteins and genotyped 768 tagging or potentially functional single nucleotide polymorphisms (SNPs) across 33 candidate gene regions in 401 Afro-Caribbeans older than 18 years belonging to 7 multi generational pedigrees (mean family size 51, range 21-113, 3,426 relative pairs). All lipoproteins were significantly heritable (P<0.05). Gender-specific analysis showed that heritability for triglycerides was much higher (P<0.01) in women than in men (women, 0.62+/-0.18, P<0.01; men, 0.13+/-0.17, P>0.10), but the heritability for LDL cholesterol (LDL-C) was higher (P<0.05) in men than in women (men, 0.79+/-0.21, P<0.01; women, 0.39+/-0.12, P<0.01). The top 14 SNPs that passed the false discovery rate threshold in the families were then tested for replication in an independent population-based sample of 1,750 Afro-Caribbean men aged 40+ years. Our results revealed significant associations for three SNPs in two genes (rs5929 and rs6511720 in LDLR and rs7517090 in PCSK9) and LDL-C in both the family study and in the replication study. Our findings suggest that LDLR and PCSK9 variants may contribute to a variation in LDL-C among African ancestry individuals. Future sequencing and functional studies of these loci may advance our understanding of genetic factors contributing to LDL-C in African ancestry populations. PMID- 20308433 TI - A comparison of 11 o'clock versus oblique femoral tunnels in the anterior cruciate ligament-reconstructed knee: knee kinematics during a simulated pivot test. AB - BACKGROUND: Traditionally, a standard femoral tunnel for a single-bundle anterior cruciate ligament (ACL) reconstruction is positioned 6 to 7 mm anterior to the posterior wall at an 11 o'clock orientation in the femoral notch (right knee). However, some surgeons have advocated placing the femoral tunnel at a more oblique orientation at or near the femoral footprint of the ACL's posterolateral bundle (at approximately 9:30 to 10 o'clock in the notch) to provide the graft with a better mechanical advantage for controlling tibial rotation and eliminating the pivot shift. HYPOTHESIS: Moving the femoral tunnel from the standard location to an oblique position in the femoral notch will significantly reduce the magnitude of a simulated pivot shift. STUDY DESIGN: Controlled laboratory study. METHODS: Internal-external tibial rotation and anteroposterior (AP) displacement of the lateral tibial plateau were measured in 17 fresh-frozen cadaveric knees during a simulated pivot-shift event with a single-bundle ACL reconstruction placed in standard and oblique femoral tunnels. Baseline kinematic measurements were taken with the graft tensioned to restore intact AP knee laxity at 30 degrees of flexion. The measurements were repeated as graft tension was decreased to produce approximately 2-mm incremental increases in laxity (up to +10 mm). Correlations between lateral tibial plateau displacement and tibial rotation during the pivot shift were determined for both tunnels. RESULTS: There were no significant differences in tibial rotations or tibial plateau displacements during the pivot shift between standard and oblique femoral tunnels when the graft was tensioned to restore intact knee laxity. The relationship between pivot-shift magnitude and AP laxity was highly linear for each knee specimen over the range of laxities tested; the mean slopes for anteromedial (AM) and posterolateral (PL) tunnels were not significantly different. There were near perfect linear correlations (mean r2 >.98) between lateral plateau displacement and tibial rotation for both femoral tunnel positions; the slope of the regression line was not significantly different between tunnels. CONCLUSION: Moving the femoral tunnel from the standard location to a more oblique position in the notch did not significantly alter pivot-shift kinematics. Lateral plateau displacement was strongly correlated with tibial rotation, and either can be used to quantify the pivot shift. Clinical Relevance The rationale for placing the femoral tunnel at an oblique position in the notch to reduce the pivot shift is questioned. PMID- 20308434 TI - Biomechanical evaluation of shear force vectors leading to injury of the biceps reflection pulley: a biplane fluoroscopy study on cadaveric shoulders. AB - BACKGROUND: The clinical importance of the biceps reflection pulley (BRP), which stabilizes the long head of the biceps tendon (LHB) as it exits the joint, has been shown. However, there is controversy on the pathomechanism of injury to the BRP. The angular orientation of the LHB relative to its origin and distal course changes with joint positions and may place the BRP at risk for injury. PURPOSE: To measure the course of the LHB in common arm positions and to determine the shear and normal (stabilizing) force vectors as well as the excursion of the LHB. STUDY DESIGN: Descriptive laboratory study. METHODS: The LHBs of 8 fresh-frozen cadaveric shoulders were marked with arthroscopically injected microbeads and mounted in a custom-built shoulder rig. Data for neutral arm position, forward flexion, and abduction were collected in internal, neutral, and external rotation using biplane fluoroscopy. Bone and LHB position were reconstructed in 3 dimensions. RESULTS: The shear component of the resulting vector was significantly higher during internal (28.4% +/- 18.1%) compared with external rotation (18.9% +/- 9.7%; P = .0157) and was highest in neutral arm position with internal rotation (39.2% +/- 12.7%) and forward flexion with neutral rotation (36.2% +/- 10.7%). The normal force vector, stabilizing the LHB, was significantly higher in abduction (55.2% +/- 9.6%) compared with forward flexion (39.1% +/- 12.4%; P <.0001) and neutral positions (39.1% +/- 11.4%; P <.0001). The LHB excursion was significantly lower for neutral arm positions (0.7 +/- 6.0 mm) compared with forward flexion (12.6 +/- 8.3 mm; P <.0001) and abduction (12.0 +/- 6.5 mm; P <.0001). CONCLUSION: Increased shear load at forward flexion with internal or neutral arm rotation and internal rotation at neutral arm position may cause injury to the BRP. Additionally, a sawing mechanism caused by the 12-mm linear excursion combined with a load of the LHB through the BRP during elevation may also lead to lesions. CLINICAL RELEVANCE: Knowledge of the pathomechanisms of BRP injury may help in developing specific treatment and rehabilitation strategies as well as tests for physical examination. PMID- 20308435 TI - Science to practice: will randomized prospective clinical trials be necessary for RF ablation of large liver tumors with liposomal doxorubicin? PMID- 20308436 TI - CT and US in the diagnosis of appendicitis: an argument for CT. PMID- 20308438 TI - Pediatric appendicitis: an argument for US. PMID- 20308439 TI - Compliance with Fleischner Society guidelines for management of lung nodules: lessons and opportunities. PMID- 20308440 TI - Part-solid nodules: two steps forward.... PMID- 20308441 TI - Net assets: PowerPoint pearls for radiology presentations. Part I. PMID- 20308442 TI - Update on the use of MR for assessment and diagnosis of psychiatric diseases. AB - The lack of quantitative objective measures of psychiatric diseases such as anxiety and depression is one reason that the causative factors of psychiatric diseases remain obscure. The fact that human behavior is complex and cannot be easily tested in laboratories or reproduced in animal models further complicates our understanding of psychiatric diseases. During the past 3 decades, several magnetic resonance (MR)-based tools such as MR morphometry, diffusion-tensor imaging, functional MR imaging, and MR spectroscopy have yielded findings that provide tangible evidence of the neurobiologic manifestations of psychiatric diseases. In this article, we summarize major MR findings of schizophrenia, bipolar disorder, anxiety disorders, and attention deficit-hyperactivity disorder as examples to illustrate the promise that MR techniques hold for not only revealing the neurobiological underpinnings of psychiatric disorders but also enhancing our understanding of healthy human behavior. However, many radiologists remain skeptical about the diagnostic value of MR in psychiatric disease. Many inconsistent, noncomparable reports in the literature contribute to this skepticism. The aims of this article are to (a) illustrate the most reported MR findings of major psychiatric disorders such as schizophrenia, mood disorders, anxiety disorders, and attention deficit-hyperactivity disorder; (b) inform radiologists of the potential roles of MR imaging in psychiatric imaging research; and (c) discuss several confounding factors in the design and interpretation of MR imaging findings in psychiatry. PMID- 20308443 TI - Decrease in breast density in the contralateral normal breast of patients receiving neoadjuvant chemotherapy: MR imaging evaluation. AB - PURPOSE: To investigate the change of breast density with quantitative magnetic resonance (MR) imaging in the contralateral normal breast of patients receiving neoadjuvant chemotherapy. MATERIALS AND METHODS: This study was approved by the institutional review board and was HIPAA compliant. Informed consent was obtained. Fifty-four patients with breast cancer (mean age, 47 years; age range, 30-74 years) treated with NAC protocol and enrolled in a breast MR imaging research study were studied. The density in the contralateral normal breast was analyzed by using an MR imaging-based segmentation method. The effect of chemotherapy on the change of density following the doxorubicin and cyclophosphamide (AC) and the AC and taxane regimen was evaluated. The dependence on age was investigated by using a multivariate regression model. RESULTS: In patients who underwent both AC and taxane follow-up, the mean percentage of change from the individual's baseline density was -10% (95% confidence interval: 12.8%, -7.2%) after AC and -12.7% (95% confidence interval: -16%, -9.4%) after AC and taxane. In patients who underwent both follow-up studies after one to two and four cycles of AC, the mean percentage of change was -9.4% (95% confidence interval: -13.5%, -5.3%) after one to two cycles of AC and -14.7% (95% confidence interval: -20.6%, -8.7%) after four cycles of AC. The percentage reduction of density was significantly dependent on age. Patients younger than 40 years had a greater reduction after chemotherapy than patients older than 55 years (P = .01). CONCLUSION: By using three-dimensional MR imaging, patients receiving chemotherapy showed reduction of breast density, and the effects were significant after initial treatment with one to two cycles of the AC regimen. PMID- 20308444 TI - Bicuspid aortic valve: four-dimensional MR evaluation of ascending aortic systolic flow patterns. AB - PURPOSE: To use time-resolved three-dimensional phase-contrast magnetic resonance (MR) imaging, also called four-dimensional flow MR imaging, to evaluate systolic blood flow patterns in the ascending aorta that may predispose patients with a bicuspid aortic valve (BAV) to aneurysm. MATERIALS AND METHODS: The HIPAA compliant protocol received institutional review board approval, and informed consent was obtained. Four-dimensional flow MR imaging was used to assess blood flow in the thoracic aorta of 53 individuals: 20 patients with a BAV, 25 patients with a tricuspid aortic valve (TAV), and eight healthy volunteers. The Fisher exact test was used to evaluate the significance of flow pattern differences. RESULTS: Nested helical flow was seen at peak systole in the ascending aorta of 15 of 20 patients with a BAV but in none of the healthy volunteers or patients with a TAV. This flow pattern was seen both in patients with a BAV with a dilated ascending aorta (n = 6) and in those with a normal ascending aorta (n = 9), was seen in the absence of aortic stenosis (n = 5), and was associated with eccentric systolic flow jets in all cases. Fusion of right and left leaflets gave rise to right-handed helical flow and right-anterior flow jets (n = 11), whereas right and noncoronary fusion gave rise to left-handed helical flow with left-posterior flow jets (n = 4). CONCLUSION: Four-dimensional flow MR imaging showed abnormal helical systolic flow in the ascending aorta of patients with a BAV, including those without aneurysm or aortic stenosis. Identification and characterization of eccentric flow jets in these patients may help identify those at risk for development of ascending aortic aneurysm. PMID- 20308445 TI - IN-1233, an ALK-5 inhibitor: prevention of granulation tissue formation after bare metallic stent placement in a rat urethral model. AB - PURPOSE: To evaluate the efficacy of an activin receptor-like kinase-5 inhibitor, IN-1233, for the prevention of tissue hyperplasia after bare stent placement in a rat urethral model. MATERIALS AND METHODS: Procedures were performed in accordance with the National Institutes of Health guidelines for humane handling of animals; approval of the committee of animal research was obtained. In 20 Sprague-Dawley male rats (weight range, 300-350 g), a self-expanding metallic bare stent was inserted in the urethra by using fluoroscopic guidance. One group of 10 rats (group A) was treated with IN-1233, the other group of 10 rats (group B) received no treatment. Retrograde urethrography was performed 4 and 8 weeks after stent placement. All rats were sacrificed at 8 weeks for histologic analysis. RESULTS: Stent placement was technically successful in all rats. The average stent diameter was significantly larger in group A compared with group B at follow-up retrograde urethrography performed 4 (P = .006) and 8 (P < .001) weeks after stent placement. At histologic analysis, the percentage of granulation tissue area (P < .001), thickness of submucosal fibrosis (P < .001), and number of epithelial layers (P < .001) were significantly decreased in group A compared with group B. Inflammatory cell infiltration (P < .001) was significantly increased in group A compared with group B. CONCLUSION: IN-1233 is effective for the prevention of granulation tissue formation after bare metallic stent placement in a rat urethral model. PMID- 20308446 TI - Colorectal and extracolonic cancers detected at screening CT colonography in 10,286 asymptomatic adults. AB - PURPOSE: To retrospectively determine the detection rates, clinical stages, and short-term patient survival for all unsuspected cancers identified at screening computed tomographic (CT) colonography, including both colorectal carcinoma (CRC) and extracolonic malignancies. MATERIALS AND METHODS: From April 2004 through March 2008, prospective colorectal and extracolonic interpretation was performed in 10,286 outpatient adults (5388 men, 4898 women; mean age, 59.8 years) undergoing screening CT colonography at two centers in this institutional review board-approved, HIPAA-compliant study. For all histologically proved, clinically unsuspected cancers detected at CT colonography that were identified at retrospective review of the medical records, the stage of disease, treatment, and clinical outcome were analyzed. Benign neoplasms (including advanced colorectal adenomas), symptomatic lesions, and tumors without pathologic proof were excluded. Statistical analysis was performed with Fisher exact test and two sample z test. RESULTS: Unsuspected cancer was confirmed in 58 (0.56%) patients (33 women, 25 men; mean age, 60.8 years), which included invasive CRC in 22 patients (0.21%) and extracolonic cancer in 36 patients (0.35%). Extracolonic malignancies included renal cell carcinoma (n = 11), lung cancer (n = 8), non Hodgkin lymphoma (n = 6), and a variety of other tumors (n = 11). Cancers in 31 patients (53.4%) were stage I or localized. At the most recent clinical follow-up (mean, 30.0 months +/- 11.8 [standard deviation]; range, 12-56 months), three patients (5.2%) had died of their cancer. CONCLUSION: The overall detection rate of unsuspected cancer is approximately one per 200 asymptomatic adults undergoing routine screening CT colonography, including about one invasive CRC per 500 cases and one extracolonic cancer per 300 cases. Detection and treatment at an early presymptomatic stage may have contributed to the favorable outcome. PMID- 20308447 TI - Prostate cancer: value of multiparametric MR imaging at 3 T for detection- histopathologic correlation. AB - PURPOSE: To determine utility of multiparametric imaging performed at 3 T for detection of prostate cancer by using T2-weighted magnetic resonance (MR) imaging, MR spectroscopy, and dynamic contrast material-enhanced MR imaging, with whole-mount pathologic findings as reference standard. MATERIALS AND METHODS: This prospectively designed, HIPAA-compliant, single-institution study was approved by the local institutional review board. Seventy consecutive patients (mean age, 60.4 years; mean prostate-specific antigen level, 5.47 ng/mL [5.47 microg/L]; range, 1-19.9 ng/mL [1-19.9 microg/L]) were included; informed consent was obtained from each patient. All patients had biopsy-proved prostate cancer, with a median Gleason score of 7 (range, 6-9). Images were obtained by using a combination of six-channel cardiac and endorectal coils. MR imaging and pathologic findings were evaluated independently and blinded and then correlated with histopathologic findings by using side-by-side comparison. Analyses were conducted with a raw stringent approach and an alternative neighboring method, which accounted for surgical deformation, shrinkage, and nonuniform slicing factors in pathologic specimens. Generalized estimating equations (GEEs) were used to estimate the predictive value of region-specific, pathologically determined cancer for all three modalities. This approach accounts for the correlation among multiple regions in the same individual. RESULTS: For T2 weighted MR imaging, sensitivity and specificity values obtained with stringent approach were 0.42 (95% confidence interval [CI]: 0.36, 0.47) and 0.83 (95% CI: 0.81, 0.86), and for the alternative neighboring approach, sensitivity and specificity values were 0.73 (95% CI: 0.67, 0.78) and 0.89 (95% CI: 0.85, 0.93), respectively. The combined diagnostic accuracy of T2-weighted MR imaging, dynamic contrast-enhanced MR imaging, and MR spectroscopy for peripheral zone tumors was examined by calculating their predictive value with different combinations of techniques; T2-weighted MR imaging, dynamic contrast-enhanced MR imaging, and MR spectroscopy provided significant independent and additive predictive value when GEEs were used (P < .001, P = .02, P = .002, respectively). CONCLUSION: Multiparametric MR imaging (T2-weighted MR imaging, MR spectroscopy, dynamic contrast-enhanced MR imaging) of the prostate at 3 T enables tumor detection, with reasonable sensitivity and specificity values. PMID- 20308448 TI - Effect of reduced radiation CT protocols on the detection of renal calculi. AB - PURPOSE: To determine the effect of reduced radiation (tube charge, measured as milliamperes per second) protocols on the sensitivity and specificity of multidetector computed tomography (CT) in the detection of renal calculi. MATERIALS AND METHODS: This Health Insurance Portability and Accountability Act compliant human cadaveric study was approved by the Department of Anatomic Pathology with strict adherence to the university policy for handling donor specimens. Three to five renal stones (range, 2.0-4.0 mm) were randomly placed in 14 human cadaveric kidneys and scanned with a 16-detector CT scanner at 100, 60, and 30 mAs while maintaining other imaging parameters as constant. Following acquisition, images were reviewed independently by two radiologists who were blinded to the location and presence of renal calculi. Interobserver agreement was measured with kappa statistics. The McNemar test was used to compare the sensitivity and specificity between different radiation settings for each reader. RESULTS: Specificity for both readers ranged from 105 (0.95; 95% confidence interval [CI]: 0.90, 0.99) to 109 (0.99; 95% CI: 0.95, 1.0) of 110 without significant differences between 30 and 60 mAs to the standard 100 mAs (P = .500 to >.999). Sensitivity ranged from 42 (0.74; 95% CI: 0.60, 0.84) to 48 (0.84; 95% CI: 0.72, 0.93) of 57, also without significant differences (P = .070 to >.999). When renal calculi detection rates were analyzed by size, 3.0-4.0-mm stones were detected well at all tube charge settings, ranging from 86%-90% (n = 21 for 3.0 mm stones) to 95%-100% (n = 19 for 4.0-mm stones). However, 2.0-mm stones were poorly detected at all tube charge settings (29%-59%; 5-10 of 17). Overall interobserver agreement for stone detection was excellent, with kappa = 0.862. CONCLUSION: Decreasing the tube charge from 100 to 30 mAs resulted in similar detection of renal stones while reducing patient radiation exposure by as much as 70%. Multidetector CT scanning parameters should be tailored to minimize radiation exposure to the patients while helping detect clinically significant renal stones. PMID- 20308449 TI - Anterior cruciate ligament reconstruction by using bioabsorbable femoral cross pins: MR imaging findings at follow-up and comparison with clinical findings. AB - PURPOSE: To determine the frequency of imaging findings and complications related to bioabsorbable femoral cross pins at follow-up magnetic resonance (MR) imaging studies after anterior cruciate ligament (ACL) reconstruction and compare these MR imaging findings with clinical evaluation findings. MATERIALS AND METHODS: The institutional review board approved this retrospective study, and informed consent was waived. Follow-up MR imaging studies (average, 26 months after surgery) in 218 patients with prior ACL reconstruction were retrospectively reviewed. Cross-pin fracture, posterior transcortical breach, migration, resorption, and lateral prominence of cross pins, as well as the cross-pin angle relative to the transepicondylar line, were investigated on MR images. The clinical evaluation included Lachman, anterior drawer, and pivot shift tests, as well as assessment for joint tenderness. RESULTS: Fracture, posterior transcortical breach, migration, and lateral prominence of cross pins were excluded from analysis when at least one cross pin was completely resorbed (n = 16 patients). Forty-five fractured cross pins were seen in 35 (17%) of 202 patients. The posterior femoral cortex was breached in 57 (28%) of 202 patients. Migration of fractured pin fragments occurred in 12 (6%) of 202 patients. There was a significant relationship between fractures and posterior breach of cross pins (P = .001), as well as between cross-pin angles and fractures (P = .002). Both cross pins were completely resorbed in 12 (6%) of 218 patients (average time since surgery, 53 months; range, 8-92 months). No significant association was found between any MR imaging finding related to cross pins and clinical test findings. CONCLUSION: Fracture and posterior transcortical breach of bioabsorbable femoral cross pins, commonly seen at follow-up MR imaging studies, do not correlate with clinical findings of joint instability or pain. Posteriorly angulated cross pins and posterior transcortical breach are significantly associated with cross-pin fractures. PMID- 20308450 TI - Functional MR imaging or Wada test: which is the better predictor of individual postoperative memory outcome? AB - PURPOSE: To retrospectively determine whether blood oxygen level-dependent functional magnetic resonance (MR) imaging can aid prediction of postoperative memory changes in epileptic patients after temporal lobe surgery. MATERIALS AND METHODS: This study was approved by the local ethics committee, and informed consent was obtained from all patients. Data were analyzed from 25 patients (12 women, 13 men; age range, 19-52 years) with refractory epilepsy in whom temporal lobe surgery was performed after they underwent preoperative functional MR imaging, the Wada test, and neuropsychological testing. The functional MR imaging protocol included three different memory tasks (24-hour delayed recognition, encoding, and immediate recognition). Individual activations were measured in medial temporal lobe (MTL) regions of both hemispheres. The prognostic accuracy of functional MR imaging for prediction of postoperative memory changes was compared with the accuracy of the Wada test and preoperative neuropsychological testing by using a backward multiple regression analysis. RESULTS: An equation that was based on left functional MR imaging MTL activation during delayed recognition, side of the epileptic focus, and preoperative global verbal memory score was used to correctly predict worsening of verbal memory in 90% of patients. The right functional MR imaging MTL activation did not substantially correlate with the nonverbal memory outcome, which was only predicted by using the preoperative nonverbal global score. Wada test data were not good predictors of changes in either verbal or nonverbal memory. CONCLUSION: Findings suggest that functional MR imaging activation during a delayed-recognition task is a better predictor of individual postoperative verbal memory outcome than is the Wada test. PMID- 20308451 TI - Second-opinion consultations in neuroradiology. AB - PURPOSE: To assess the patient care benefit of a recently implemented institutional policy requiring official second-opinion consultation for all studies performed outside the institution. MATERIALS AND METHODS: The institutional review board approved the retrospective review of patient data for this HIPAA-compliant study and waived the need for individual informed consent. The second-opinion consultation reports for outside neuroradiology studies finalized by subspecialty-trained neuroradiologists within calendar year 2008 were compared with the outside reports provided with the images. The reports were categorized by using a five-point scale: 1 indicated no difference in interpretation; 2, clinically unimportant difference in detection; 3, clinically unimportant difference in interpretation; 4, clinically important difference in detection; and 5, clinically important difference in interpretation. Clinically important differences were defined as those likely to change patient care or diagnoses. Statistical comparisons were performed by using two-sample continuity corrected Z tests with two-sided alternatives. Bonferroni corrections were performed when more than two rates were compared. Confidence intervals for all rates were constructed by using the score interval along with the Yates continuity correction. RESULTS: Of 7465 studies, 4534 (60.7%) had an outside report for comparison. There were 347 (7.7%) instances with clinically important differences. Of these 347 discrepancies, 233 (67.1%) were category 4 and 114 (32.9%) were category 5. When the final diagnosis was determined from pathology reports, clinical assessments, and/or imaging follow-up, the second-opinion consultation was noted to be correct in 163 (84.0%) of 194 studies with category 4 or 5 discrepancies. CONCLUSION: A 7.7% rate of discrepant interpretations (347 of 4534 studies) was noted for a service offering second-opinion consultations for outside examinations. Most were discrepancies in detecting abnormalities rather than in interpreting identified findings. When a definitive diagnosis was obtainable, the second-opinion consultation was more accurate in 84% of studies. Review of outside studies benefits patient care. PMID- 20308452 TI - Certainty of stroke diagnosis: incremental benefit with CT perfusion over noncontrast CT and CT angiography. AB - PURPOSE: To systematically evaluate the diagnostic benefits and inter- and intraobserver reliability of an incremental computed tomographic (CT) protocol in the confirmation of clinically suspected stroke, with combined imaging and clinical data as the reference standard. MATERIALS AND METHODS: Institutional review board approval was obtained, and participants gave informed consent. A total of 191 patients (mean age, 67 years +/- 16 [standard deviation]; 105 men) with strokelike symptoms of no more than 3 hours duration were recruited. Blinded review was performed by four readers with limited stroke imaging experience. Diagnostic confidence was recorded on a five-point scale. Logistic regression analysis was used to calculate the difference between the real and observed diagnoses, adjusting for confidence. Predictive effects of observed diagnostic performance and confidence score were quantified with the entropy r(2) value. Sensitivity, specificity, and confidence intervals were calculated while accounting for multiple reader assessments. Receiver operating characteristic (ROC) analyses, including area under the ROC curve, were conducted for three modalities in combination with confidence score. Inter- and intraobserver agreement was established with the Cohen kappa statistic. RESULTS: The final diagnosis was infarct in 64% of the patients, transient ischemic attack in 18%, and stroke mimic in 17%. Large-vessel occlusion occurred in 70% of the patients with an infarct. Sensitivity for stroke determination with noncontrast CT, CT angiography, and CT perfusion increased by 12.4% over that with noncontrast CT and CT angiography and by 18.2% over that with only noncontrast CT for a confidence level of 4 or higher. The incremental protocol was more likely to enable confirmation of clinical stroke diagnosis (odds ratio, 13.3) than was noncontrast CT and CT angiography (odds ratio, 6.4) or noncontrast CT alone (odds ratio, 3.3), The area under the ROC curve was 0.67 for the combination of noncontrast CT and confidence score, 0.72 for the combination of CT angiography and confidence score, and 0.81 for the combination of CT perfusion and confidence score. Inter- and intraobserver agreement increased with progressive sequence use. CONCLUSION: An incremental stroke protocol that includes CT perfusion increases diagnostic performance for stroke diagnosis and inter- and intraobserver agreement. PMID- 20308453 TI - Improved detection of active multiple sclerosis lesions: 3D subtraction imaging. AB - PURPOSE: To examine the benefits of using near-isotropic single-slab three dimensional (3D) magnetic resonance (MR) imaging for the creation of subtraction images and to evaluate their performance in the detection of active multiple sclerosis (MS) brain lesions in comparison with two-dimensional (2D) subtraction images. MATERIALS AND METHODS: The study protocol was approved by the local ethics review board and all subjects gave written informed consent before investigation. Three-dimensional MR sequences, including double inversion recovery, fluid-attenuated inversion recovery, T2-weighted, and T1-weighted magnetization-prepared rapid acquisition gradient-echo (MP-RAGE), and corresponding 2D sequences were performed twice in 14 patients (eight women, six men; mean age, 37.6 years) with MS and nine age-matched healthy control subjects (three women, six men; mean age, 31.7 years). Active lesions were scored by two independent raters, followed by a consensus reading. Lesion counts were evaluated by using negative binomial regression; interrater agreement was evaluated by using intraclass correlation coefficient. RESULTS: Three-dimensional subtraction images had less residual misregistration and flow artifacts and depicted higher numbers of active lesions with greater interobserver agreement compared with 2D subtraction images. Among the 3D sequences, MP-RAGE subtraction imaging enabled detection of a significantly higher mean number of positive active MS lesions compared with 2D subtraction imaging (2.8 versus 1.7, P = .012), particularly infratentorial lesions (0.6 vs 0.1, P < .05), and a substantially higher (nonsignificant) mean number of small (<3 mm) lesions (0.6 vs 0.1, P > .05). CONCLUSION: Three-dimensional subtraction imaging, after image registration, produced better image quality, leading to increased detection of active MS lesions with greater interobserver agreement in comparison with 2D subtraction imaging; 3D MP-RAGE subtraction imaging represents a promising technique to increase sensitivity in ascertaining lesion dissemination in time and increase the power of MR imaging metrics for the evaluation of treatment effects in clinical trials. PMID- 20308454 TI - Does multidetector CT attenuation change in colon cancer liver metastases treated with 90Y help predict metabolic activity at FDG PET? AB - PURPOSE: To evaluate the correlation between change in attenuation and tumor metabolic activity assessed by using fluorodeoxyglucose (FDG) positron emission tomography (PET) in colon cancer liver metastases treated with yttrium 90 ((90)Y) radioembolization. MATERIALS AND METHODS: This Health Insurance Portability and Accountability Act-compliant retrospective study was approved by the institutional review board; patient informed consent was waived. Unresectable chemorefractory colon cancer liver metastases treated with (90)Y radioembolization in 28 patients were evaluated at pre- and posttreatment multidetector computed tomographic (CT) and FDG PET scans. Maximum cross sectional diameter, volume, and overall attenuation of target lesions were calculated. The percentage change (%Delta) in these parameters after treatment was calculated and correlated with the standardized uptake value (SUV) analysis at FDG PET. The accuracy of the radiologic parameters in helping predict response to treatment at FDG PET was assessed. Data were analyzed by using the Student t, Wilcoxon matched pair, Mann-Whitney, Spearman rank correlation, and chi(2) tests. The significance level was set at .05. RESULTS: Seventy-four metastatic lesions in 10 women and 18 men (mean age, 61.5 years +/- 14.3 [standard deviation]) were evaluated. Mean follow-up interval for multidetector CT after treatment was 30 days. A significant reduction in maximum cross-sectional diameter, volume, and attenuation was observed from pre- to posttreatment multidetector CT (P < .05). The %Delta in attenuation had higher correlation with %Delta in SUV (r = 0.61) than diameter (r = 0.39) or volume (r = 0.49) and also predicted the metabolic activity at FDG PET with higher sensitivity (P < .001). By using a threshold level of a reduction in attenuation of 15% or greater, attenuation showed 84.2% sensitivity and 83.3% specificity in predicting response at FDG PET evaluation. CONCLUSION: Changes in attenuation of colon cancer liver metastases treated with (90)Y radioembolization correlate highly with metabolic activity at FDG PET and may be useful as an early surrogate marker for assessing treatment response. PMID- 20308455 TI - Skeletal trauma in child abuse: detection with 18F-NaF PET. AB - PURPOSE: To evaluate the sensitivity of fluorine 18-labeled sodium fluoride ((18)F-NaF) positron emission tomography (PET) for assessment of skeletal trauma in pediatric patients suspected of having been abused and to compare the diagnostic performance of this examination with that of high-detail skeletal survey. MATERIALS AND METHODS: The institutional review board approved this retrospective study and determined that it was in accordance with regulations of HIPAA privacy rule 45, Code of Federal Regulations parts 160 and 164, and that the criteria for waived patient authorization were met. The baseline skeletal survey and PET images obtained in 22 patients younger than 2 years between September 2007 and January 2009 were reviewed. Fourteen patients also underwent follow-up skeletal survey. The PET images were interpreted by two pediatric nuclear medicine physicians. The initially obtained skeletal survey images were interpreted blindly by a pediatric radiologist. A second pediatric radiologist interpreted the follow-up skeletal survey images in conjunction with the baseline survey images and rendered a final interpretation for the 14 patients in whom both baseline and follow-up skeletal survey data were available, which served as the reference standard. RESULTS: A total of 156 fractures were detected at baseline skeletal survey, and 200 fractures were detected at PET. Compared with the reference standard (findings in the 14 patients who underwent baseline and follow-up skeletal survey), PET had sensitivities of 85% for the detection of all fractures, 92% for the detection of thoracic fractures (ribs, sternum, clavicle, and scapula), 93% for the detection of posterior rib fractures, and 67% for the detection of classic metaphyseal lesions (CMLs), defined as a series of microfractures across the metaphysis. Compared with the reference standard, baseline skeletal survey had sensitivities of 72% for the detection of all fractures, 68% for the detection of thoracic fractures, 73% for the detection of posterior rib fractures, and 80% for the detection of CMLs. CONCLUSION: (18)F-NaF PET had greater sensitivity in the overall detection of fractures related to child abuse than did baseline skeletal survey. (18)F-NaF PET was superior in the detection of rib fractures in particular. Thus, (18)F-NaF PET is an attractive choice for evaluation of suspected child abuse, an application in which high sensitivity is desirable. Because of the lower sensitivity of PET in the detection of CMLs, a characteristic fracture in child abuse, initial radiographic evaluation remains necessary. PMID- 20308456 TI - Pediatric and adolescent lymphoma: comparison of whole-body STIR half-Fourier RARE MR imaging with an enhanced PET/CT reference for initial staging. AB - PURPOSE: To compare the diagnostic performance of rapid whole-body anatomic magnetic resonance (MR) staging of pediatric and adolescent lymphoma to an enhanced positron emission tomographic (PET)/computed tomographic (CT) reference standard. MATERIALS AND METHODS: Ethical permission was given by the University College London Hospital ethics committee, and informed written consent was obtained from all participants and/or parents or guardians. Thirty-one subjects (age range, 7.3-18.0 years; 18 male, 11 female) with histologically proved lymphoma were prospectively recruited. Pretreatment staging was performed with whole-body short inversion time inversion-recovery (STIR) half-Fourier rapid acquisition with relaxation enhancement (RARE) MR imaging, fluorine 18 fluorodeoxyglucose PET/CT, and contrast agent-enhanced chest CT. Twenty-six subjects had posttreatment PET/CT and compromised our final cohort. Eleven nodal and 11 extranodal sites per patient were assessed on MR imaging by two radiologists in consensus, with a nodal short-axis threshold of >1 cm and predefined extranodal positivity criteria. The same sites were independantly evaluated by two nuclear medicine physicians on PET/CT images. Disease positivity was defined as a maximum standardized uptake value >2.5 or nodal size >1 cm. An unblinded expert panel reevaluated the imaging findings, removing perceptual errors, and derived an enhanced PET/CT reference standard (taking into account chest CT and 3-month follow-up imaging) against which the reported and intrinsic performance of MR imaging was assessed by using the kappa statistic. RESULTS: There was very good agreement between MR imaging and the enhanced PET/CT reference standard for nodal and extranodal staging (kappa = 0.96 and 0.86, respectively) which improved following elimination of perceptual errors (kappa = 0.97 and 0.91, respectively). The sensitivity and specificity of MR imaging (following removal of perceptual error) were 98% and 99%, respectively, for nodal disease and 91% and 99%, respectively, for extranodal disease. CONCLUSION: Whole body STIR half-Fourier RARE MR imaging of pediatric and adolescent lymphoma can accurately depict nodal and extranodal disease and may provide an alternative nonionizing imaging method for anatomic disease assessment at initial staging. PMID- 20308457 TI - Dual-modality breast tomosynthesis. AB - PURPOSE: To evaluate the clinical performance of a hybrid scanner that uses dual modality tomosynthesis (DMT) and technetium 99m sestamibi to provide coregistered anatomic and functional breast images in three dimensions. MATERIALS AND METHODS: A prospective pilot evaluation of the scanner was performed in women scheduled to undergo breast biopsy after institutional review board approval and informed consent were obtained. All subject data were handled in compliance with the rules and regulations concerning the privacy and security of protected health information under HIPAA. The study included 17 women (mean age, 53 years; age range, 44-67 years) and 21 biopsy-sampled lesions. Results of DMT scanning were compared with histopathologic results for the 21 lesions. RESULTS: Of the 21 lesions, seven were malignant, and 14 were benign. Among the 13 subjects with one lesion each, three had positive biopsy results, and 10 had negative biopsy results. Among the four subjects with two lesions, the biopsy results were as follows: bilateral in one, both negative; bilateral in one, both positive; unilateral in two, one positive and one negative. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of DMT scanning were 86%, 100%, 100%, 93%, and 95%, respectively. CONCLUSION: Pilot clinical evaluation of the DMT scanner suggests that it is a feasible and accurate method with which to detect and diagnose breast cancer. Systems such as the DMT scanner that are designed specifically for three-dimensional multimodality breast imaging could make possible some of the advances in tumor detection, localization, and characterization of breast cancer that are now being observed with whole-body three-dimensional hybrid systems, such as positron emission tomography/computed tomography (CT) or single photon emission computed tomography/CT. PMID- 20308458 TI - Compliance with Fleischner Society guidelines for management of small lung nodules: a survey of 834 radiologists. AB - PURPOSE: To determine the familiarity of radiologists with the Fleischner Society guidelines for management of small lung nodules and to assess whether their decisions for nodule management are consistent with these recommendations. MATERIALS AND METHODS: Institutional review board exemption was granted for this electronic survey, which was sent to a sample of 7000 radiologists randomly selected from the Radiological Society of North America (RSNA) directory. Three clinical scenarios for nodule management were presented. Information about policies and guidelines for nodule management, awareness of published guidelines, and respondent demographics was obtained. Associations between these parameters and management recommendations were assessed by using a chi(2) test. Respondents were also asked about tube current settings for routine chest computed tomographic examinations and those performed solely for nodule follow-up. RESULTS: Of 834 respondents (response rate, 11.9%), 649 (77.8%) were aware of the Fleischner Society guidelines and 490 (58.8%) worked in practices that employed them or similar guidelines. Management selections were consistent with the Fleischner guidelines in 34.7%-60.8% of responses for the three scenarios. A significantly higher rate of concordance was associated with awareness of the Fleischner guidelines, presence of written policies based on them, a teaching practice setting, practice in a group with at least one member having chest radiology fellowship training, and fewer than 5 years of experience practicing radiology (P < .05 for all associations). The spectrum of tube current settings used was similar between the subgroups of respondents who were aware and those who were unaware of the Fleischner guidelines. CONCLUSION: Among survey respondents, there was high awareness and adoption of the Fleischner guidelines, but radiologists showed varying degrees of conformance with these recommendations. Future efforts are necessary to bridge the gap between awareness and implementation of these evidence-based guidelines. PMID- 20308459 TI - Hyperpolarized 3He MR for sensitive imaging of ventilation function and treatment efficiency in young cystic fibrosis patients with normal lung function. AB - PURPOSE: To assess the sensitivity of hyperpolarized helium 3 ((3)He) magnetic resonance (MR) imaging for the detection of peripheral airway obstruction in younger cystic fibrosis (CF) patients showing normal spirometric results (mean forced expiratory volume in 1 second [FEV(1)], 112% +/- 14.5 [standard deviation]) and to observe the immediate effects of a single chest physical therapy (CPT) session, thereby comparing two image quantification techniques. MATERIALS AND METHODS: Ten pediatric CF patients (age range, 8-16 years) with normal spirometric results were included in this study after approval from the local research ethics committee. Spirometry followed by proton and hyperpolarized (3)He three-dimensional lung imaging were performed with a 1.5-T MR unit before and after 20 minutes of CPT. The number of ventilation defects per image (VDI) and the ventilated lung fraction (VF), defined as the ratio of ventilated lung volume divided by total lung volume, were quantified. RESULTS: Ventilation defects were found in all patients (mean VDI, 5.1 +/- 1.9; mean global VF, 78.5% +/- 12.3; and mean peripheral VF, 75.5% +/- 17.1) despite normal spirometric results. After CPT, disparate changes in the distribution of ventilation defects were observed but the average VDI and VF did not change significantly (mean VDI, 5.1 +/- 1.1; mean global VF, 83.5% +/- 12.2; and mean peripheral VF, 80.3% +/- 12.2). There was no correlation between FEV(1) and VDI (rho = -0.041, P = .863) or global VF (rho = -0.196, P = .408) values but peripheral VF and VDI were correlated (rho = -0.563, P = .011). CONCLUSION: Although spirometric results indicate normal lung function, the mean VDI in patients (5.1) found in this study is well above the VDI in healthy subjects (1.6) reported in the literature. A single CPT session induces disparate changes in the distribution and extent of ventilation defects. PMID- 20308460 TI - Optimal scan parameters for CT fluoroscopy in lung interventional radiologic procedures: relationship between radiation dose and image quality. AB - PURPOSE: To evaluate the relationship between radiation doses and lung computed tomographic (CT) fluoroscopic scan parameters and to determine optimal scan parameters for performance of lung interventional radiologic (IR) procedures. MATERIALS AND METHODS: The institutional review board approved this prospective study, which included 32 patients with a single lung tumor; written informed consent was obtained. CT fluoroscopic images were obtained with three tube voltages (80,120,135 kV) and three tube currents (10, 20, 30 mA) in each patient. The signal-to-noise ratios (SNRs) and the contrast-to-noise ratios (CNRs) were measured quantitatively. To evaluate the feasibility of performing lung IR procedures, four readers visually scored the image quality. Acceptable CT fluoroscopic images were determined by using agreement of at least three of the four readers. The weighted CT dose index for each CT scan parameter was measured. A piecewise linear regression equation was obtained from the relationship between radiation doses and visual image scores. RESULTS: Both the SNR and the CNR improved as the radiation dose increased, leading to improvement in the image quality. Acceptable image quality was achieved in 94% (30 of 32) of patients when the radiation dose was 1.18 mGy/sec (120 kV, 10 mA) and in all patients when it was greater than 1.48 mGy/sec (135 kV, 10 mA). The piecewise linear curve showed rapid improvement in image quality until the radiation dose increased to 1.48 mGy/sec (135 kV, 10 mA). When the radiation dose was increased greater than 1.48 mGy/sec, improvement in the image quality became more gradual. CONCLUSION: Results of this study can be used to guide the determination of optimal scan parameters in lung CT fluoroscopy. PMID- 20308461 TI - H1N1 influenza: initial chest radiographic findings in helping predict patient outcome. AB - PURPOSE: To retrospectively evaluate whether findings on initial chest radiographs of influenza A (H1N1) patients can help predict clinical outcome. MATERIALS AND METHODS: Institutional review board approval was obtained; informed consent was waived. All adult patients admitted to the emergency department (May to September 2009) with a confirmed diagnosis of H1N1 influenza who underwent frontal chest radiography within 24 hours were included. Radiologic findings were characterized by type and pattern of opacities and zonal distribution. Major adverse outcome measures were mechanical ventilation and death. RESULTS: Of 179 H1N1 influenza patients, 97 (54%) underwent chest radiography at admission; 39 (40%) of these had abnormal radiologic findings likely related to influenza infection and five (13%) of these 39 had adverse outcomes. Fifty-eight (60%) of 97 patients had normal radiographs; two (3%) of these had adverse outcomes (P = .113). Characteristic imaging findings included the following: ground-glass (69%), consolidation (59%), frequently patchy (41%), and nodular (28%) opacities. Bilateral opacities were common (62%), with involvement of multiple lung zones (72%). Findings in four or more zones and bilateral peripheral distribution occurred with significantly higher frequency in patients with adverse outcomes compared with patients with good outcomes (multizonal opacities: 60% vs 6%, P = .01; bilateral peripheral opacities: 60% vs 15%, P = .049). CONCLUSION: Extensive involvement of both lungs, evidenced by the presence of multizonal and bilateral peripheral opacities, is associated with adverse prognosis. Initial chest radiography may have significance in helping predict clinical outcome but normal initial radiographs cannot exclude adverse outcome. PMID- 20308462 TI - Can vascularity at power Doppler US help predict thyroid malignancy? AB - PURPOSE: To retrospectively evaluate the diagnostic performance of power Doppler ultrasonography (US) in depicting vascularity and to determine whether the combination of vascularity and suspicious gray-scale US features is more useful in predicting thyroid malignancy than are gray-scale features alone. MATERIALS AND METHODS: This was an institutional review board-approved retrospective study, with waiver of informed consent. A total of 1083 thyroid nodules in 1024 patients (median age, 51 years; range, 16-83 years), consisting of 886 women (median age, 50 years; range, 16-83 years) and 138 men (median age, 53 years; range, 19-74 years), were included. Nodules with marked hypoechogenicity, noncircumscribed margins, microcalcifications, and taller-than-wide shape were classified as suspicious according to gray-scale US criteria. Vascularity was classified as none, peripheral, and intranodular. The diagnostic performance of gray-scale and power Doppler US features was compared and classified as follows: criterion 1, any single suspicious gray-scale US feature; criterion 2, addition of any vascularity as one of the suspicious features to criterion 1; criterion 3, addition of peripheral vascularity to criterion 1; criterion 4, addition of intranodular vascularity to criterion 1; criterion 5, addition of no vascularity to criterion 1; criterion 6, American Association of Clinical Endocrinologists and Associazione Medici Endocrinology guidelines--all hypoechoic nodules with at least one of the following US features: irregular margins, intranodular vascular spots, taller-than-wide shape, or microcalcifications. RESULTS: Of 1083 nodules, 814 were benign and 269 were malignant. Intranodular vascularity was frequently seen in benign nodules and no vascularity was more frequent in malignant nodules (P < .0001, respectively). The area under the receiver operating characteristic curve (A(z)) of criterion 1 was superior (A(z) = 0.851) to that of criteria 2 (A(z) = 0.634), 3 (A(z) = 0.752), 4 (A(z) = 0.733), 5 (A(z) = 0.718), and 6 (A(z) = 0.806) (P < .0001). CONCLUSION: Vascularity itself or a combination of vascularity and gray-scale US features was not as useful as the use of suspicious gray-scale US features alone for predicting thyroid malignancy. PMID- 20308463 TI - Nonresectable combined hepatocellular carcinoma and cholangiocarcinoma: analysis of the response and prognostic factors after transcatheter arterial chemoembolization. AB - PURPOSE: To evaluate the clinical effectiveness of transcatheter arterial chemoembolization (TACE) performed in patients with nonresectable combined hepatocellular carcinoma (HCC) and cholangiocarcinoma and analyze the prognostic factors of patient survival after TACE. MATERIALS AND METHODS: Each patient provided informed consent for TACE. The institutional review board approved the current study and waived the requirement for patient consent for this retrospective review. From 1997 to 2009, 50 patients underwent TACE for nonresectable combined HCC-cholangiocarcinoma. Tumor response was evaluated on the basis of findings on computed tomographic (CT) scans obtained a mean of 30.7 days after TACE. The survival rate and the prognostic factors of patient survival were evaluated. RESULTS: After TACE, 35 (70%) of the 50 patients were classified as responders--having either a partial response or stable disease with successful (>50%) tumor necrosis--and 15 (30%) were classified as nonresponders. Tumor response was significantly related to tumor vascularity: One (10%) of the 10 patients with hypovascular tumors and 34 (85%) of the 40 patients with hypervascular tumors were responders (P < .001). The median patient survival period was 12.3 months. Results of multivariable Cox regression analyses confirmed that tumor size (hazard ratio [HR], 2.49; P = .028), tumor vascularity (HR, 4.19; P = .001), Child-Pugh class (HR, 4.3; P = .001), and portal vein invasion (HR, 6.45; P < .001) were the independent factors associated with patient survival duration after TACE. CONCLUSION: TACE is safe and may be effective for prolonging the survival of patients with nonresectable combined HCC cholangiocarcinoma, as compared with the historically reported survivals of these patients. Tumor vascularity is highly associated with tumor response. The patient survival period after TACE for combined HCC-cholangiocarcinoma is significantly dependent on tumor size, tumor vascularity, Child-Pugh class, and presence or absence of portal vein invasion. PMID- 20308464 TI - Celiac axis and common hepatic artery variations in 5002 patients: systematic analysis with spiral CT and DSA. AB - PURPOSE: To identify and evaluate the spectrum and prevalence of celiac axis (CA) and common hepatic artery (CHA) variations by using spiral computed tomography (CT) and digital subtraction angiography (DSA). MATERIALS AND METHODS: Institutional review board approval was obtained, and the requirement for informed patient consent was waived. The findings in 5002 patients who underwent spiral CT and DSA were retrospectively evaluated. CHA was defined as an arterial trunk containing at least one segmental hepatic artery and the gastroduodenal artery. The pattern of the aortic origin of the branches of the CA and superior mesenteric arteries was analyzed. The CHA anatomy was then investigated. RESULTS: Of 15 possible types of CA variation, 13 types were identified. A normal CA was noted in 4457 (89.1%) of the 5002 patients. Twelve types of CA variation were identified in 482 (9.64%) patients. In the remaining 63 (1.26%) patients, the CA anatomy was classified as ambiguous because the CHA was absent owing to separate origins of the hepatic arteries and the gastroduodenal artery (n = 55) or because the origin of the CHA could not be determined owing to persistent anastomotic channels (n = 8). Seven CHAs originating from the normal CA had a retroportal (n = 6) or transpancreatic (n = 1) course. All eight CHAs originating from the left gastric artery passed the fissure of the ligamentum venosum. The 148 CHAs originating from the superior mesenteric artery showed diverse relationships with the pancreas--being supra-, trans-, or infrapancreatic--and the superior mesenteric-portal venous axis--being pre- or retroportal. The 20 CHAs originating from the aorta had a normal suprapancreatic preportal course. CONCLUSION: Known or newly found CA and CHA variations could be systematically described in detail. The authors propose a hypothetical anatomic model for summarizing the observed CHA variations. PMID- 20308465 TI - Hepatocellular carcinoma: CT for tumor response after transarterial chemoembolization in patients exceeding Milan criteria--selection parameter for liver transplantation. AB - PURPOSE: To retrospectively evaluate the clinical outcome of patients with hepatocellular carcinoma (HCC) who exceeded the Milan criteria, who underwent transarterial chemoembolization (TACE) before orthotopic liver transplantation (OLT), to determine the value of computed tomography (CT)-based tumor response to TACE as a preoperative selection criterion for OLT. MATERIALS AND METHODS: The study included 33 patients with HCC who exceeded the Milan criteria and underwent OLT after TACE. Informed written consent was obtained before TACE and OLT. Institutional review board approval was not required. Tumor response to TACE was evaluated at 1 month with CT according to amended Response Evaluation Criteria in Solid Tumours (RECIST) guidelines. In the explanted liver, degree of tumor necrosis (> or = 90%, 50%-89%, or < 50%), residual tumor stage and grade, and presence of microvascular invasion were assessed. Follow-up after OLT ranged from 1 to 143 months. RESULTS: After TACE, CT showed complete tumor response (CR) in 18 (55%) patients. On the explanted liver, tumor necrosis was rated 90% or greater in 20 (61%) patients, with a good correlation with CT. Microvascular invasion was observed in nine (27%) of 33 patients; none of them were reported to have a CR at CT. The 5-year cumulative survival rate after OLT was 72.5%; it was significantly (P = .003) higher in patients with a CR (94.4%) compared with patients with a partial response (PR) (45.4%) and stable disease (50%). The 5 year cumulative recurrence-free rate after OLT was 74.4%; it was not affected by the tumor nodule size and number, whereas it was significantly (P = .008) higher in patients with a CR (94.4%) compared with patients with a PR (46.7%) and stable disease (50%). CONCLUSION: In patients with HCC who exceeded the Milan criteria, a CR after TACE, on the basis of amended RECIST guidelines, is associated with excellent posttransplantation outcomes. Therefore, 1-month response to TACE assessed at CT may represent a valid selection criterion for OLT. PMID- 20308467 TI - Case 156: Inverted Meckel diverticulum. PMID- 20308468 TI - Mammographic screening: a well-recognized medical advance. PMID- 20308469 TI - Correction to the relative risk calculation for gadolinium-enhanced MR imaging and nephrogenic systemic fibrosis. PMID- 20308470 TI - Molecular characterization of the cis-prenyltransferase of Giardia lamblia. AB - Giardia lamblia, the protist that causes diarrhea, makes an Asn-linked-glycan (N glycan) precursor that contains just two sugars (GlcNAc(2)) attached by a pyrophosphate linkage to a polyprenol lipid. Because the candidate cis prenyltransferase of Giardia appears to be more similar to bacterial enzymes than to those of most eukaryotes and because Giardia is missing a candidate dolichol kinase (ortholog to Saccharomyces cerevisiae SEC59 gene product), we wondered how Giardia synthesizes dolichol phosphate (Dol-P), which is used to make N-glycans and glycosylphosphatidylinositol (GPI) anchors. Here we show that cultured Giardia makes an unsaturated polyprenyl pyrophosphate (dehydrodolichol), which contains 11 and 12 isoprene units and is reduced to dolichol. The Giardia cis prenyltransferase that we have named Gl-UPPS because the enzyme primarily synthesizes undecaprenol pyrophosphate is phylogenetically related to those of bacteria and Trypanosoma rather than to those of other protists, metazoans and fungi. In transformed Saccharomyces, the Giardia cis-prenyltransferase also makes a polyprenol containing 11 and 12 isoprene units and supports normal growth, N glycosylation and GPI anchor synthesis of a rer2Delta, srt1Delta double-deletion mutant. Finally, despite the absence of an ortholog to SEC59, Giardia has cytidine triphosphate-dependent dolichol kinase activity. These results suggest that the synthetic pathway for Dol-P is conserved in Giardia, even if some of the important enzymes are different from those of higher eukaryotes or remain unidentified. PMID- 20308471 TI - Role of UDP-glucuronosyltransferase isoforms in 13-cis retinoic acid metabolism in humans. AB - 13-cis Retinoic acid (13cisRA, isotretinoin) is an important drug in both dermatology, and the treatment of high-risk neuroblastoma. 13cisRA is known to undergo cytochrome P450-mediated oxidation, mainly by CYP2C8, but phase II metabolic pathways have not been characterized. In the present study, the glucuronidation activities of human liver (HLM) and intestinal microsomes (HIM), as well as a panel of human UDP-glucuronosyltransferases (UGTs) toward both 13cisRA and the 4-oxo metabolite, 4-oxo 13cisRA, were compared using high performance liquid chromatography. Both HLM and, to a greater extent, HIM catalyzed the glucuronidation of 13cisRA and 4-oxo 13cisRA. Based on the structures of 13cisRA and 4-oxo 13cisRA, the glucuronides formed are conjugated at the terminal carboxylic acid. Further analysis revealed that UGT1A1, UGT1A3, UGT1A7, UGT1A8, and UGT1A9 were the major isoforms responsible for the glucuronidation of both substrates. For 13cisRA, a pronounced substrate inhibition was observed with individual UGTs and with HIM. UGT1A3 exhibited the highest rate of activity toward both substrates, and a high rate of activity toward 13cisRA glucuronidation was also observed with UGT1A7. However, for both substrates, K(m) values were above concentrations reported in clinical studies. Therefore, UGT1A9 is likely to be the most important enzyme in the glucuronidation of both substrates as this enzyme had the lowest K(m) and is expressed in both the intestine and at high levels in the liver. PMID- 20308472 TI - Muscle edema. PMID- 20308473 TI - Contrast-enhanced myocardial inversion time at the null point for detection of left ventricular myocardial fibrosis in patients with dilated and hypertrophic cardiomyopathy: a pilot study. AB - OBJECTIVE: The purpose of this article is to investigate a noninvasive method for quantifying diffuse myocardial fibrosis with cardiac MRI in patients with dilated cardiomyopathy and hypertrophic cardiomyopathy. MATERIALS AND METHODS: We performed cardiac MRI on 35 patients (24 patients with dilated cardiomyopathy and 11 patients with hypertrophic cardiomyopathy) and 10 control subjects, on a clinical 1.5-T cardiac MRI scanner. Delayed hyperenhancement images were obtained 15 minutes after injection of a bolus of gadopentetate dimeglumine (0.2 mmol/kg), to identify fibrosis using an inversion recovery gradient-echo technique (inversion time scout sequence: TR, 20.8 milliseconds; TE, 1.3 milliseconds; inversion time, individually determined to null the myocardial signal [range, 85 800 milliseconds]). An inversion time mapping sequence was used to calculate the contrast-enhanced myocardial inversion time at the null point of a single midventricular slice as an index of diffuse fibrosis. RESULTS: The mean contrast enhanced myocardial inversion time at the null point was significantly shorter in the patient group than the control group (343. 7 +/- 27.9 vs 390.4 +/- 19.3 milliseconds; p < 0.0001). In the patient group, the mean contrast-enhanced myocardial inversion time at the null point was shorter in patients with dilated cardiomyopathy than in patients with hypertrophic cardiomyopathy (337.0 +/- 29.6 vs 358.6 +/- 17.1 milliseconds, p = 0.02). In the dilated cardiomyopathy group, contrast-enhanced myocardial inversion time at the null point was significantly related to the left ventricular ejection fraction (r = 0.52; p = 0.01). However, in the hypertrophic cardiomyopathy group, contrast-enhanced myocardial inversion time at the null point had only a small positive correlation with the left ventricular ejection fraction (r = 0.27; p = 0.41). CONCLUSION: Contrast-enhanced myocardial inversion time at the null point is shorter with myocardial fibrosis in patients with dilated cardiomyopathy and hypertrophic cardiomyopathy. In dilated cardiomyopathy, contrast-enhanced myocardial inversion time at the null point is inversely related to the severity of dilated cardiomyopathy. PMID- 20308474 TI - Cardiac MRI in arrhythmogenic right ventricular cardiomyopathy. AB - OBJECTIVE: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a cause of sudden cardiac death in otherwise healthy young adults. This article outlines the spectrum of MRI findings in ARVC using a combination of static and cine images. CONCLUSION: The detection of right ventricular enlargement, fatty infiltration, fibrosis, and wall motion abnormalities at MRI is useful in the diagnosis of ARVC. PMID- 20308475 TI - How not to miss or mischaracterize a renal cell carcinoma: protocols, pearls, and pitfalls. AB - OBJECTIVE: MDCT protocol optimization for renal cell carcinoma requires attention to several data acquisition, reconstruction, and display parameters. Specifically, multiple acquisitions with varying coverage, careful timing of each contrast-enhanced phase, and use of 2D and 3D multiplanar displays are required. This article reviews these parameters, supplemented by experience-based pearls and pitfalls. CONCLUSION: Proper data acquisition and utilization of postprocessing tools are essential to avoid missed diagnoses or misinterpretation when imaging renal cell carcinoma. PMID- 20308476 TI - Diffusion-weighted MRI of peripheral zone prostate cancer: comparison of tumor apparent diffusion coefficient with Gleason score and percentage of tumor on core biopsy. AB - OBJECTIVE: The objective of our study was to determine the relationship between the apparent diffusion coefficient (ADC) value on diffusion-weighted imaging (DWI) and Gleason score of prostate cancer and percentage of tumor involvement on prostate core biopsy. MATERIALS AND METHODS: We performed a retrospective study of 57 patients with biopsy-proven prostate cancer who underwent endorectal MRI with DWI between July 2007 and March 2008. Regions of interest (ROIs) were drawn on ADC maps at sites of visible tumor on DW images and ADC maps. A hierarchic mixed linear model was used to compare the ADC value of prostate cancer with the Gleason score and the percentage of tumor on core biopsy. RESULTS: Eighty-one sites of biopsy-proven prostate cancer were visible on DW images and ADC maps. The least-squares mean ADC for disease with a Gleason score of 6 was 0.860 x 10( 3) mm(2)/s (standard error of the mean [SEM], 0.036); Gleason score of 7, 0.702 x 10(-3) mm(2)/s (SEM, 0.030); Gleason score of 8, 0.672 x 10(-3) mm(2)/s (SEM, 0.057); and Gleason score of 9, 0.686 x 10(-3) mm(2)/s (SEM, 0.067). Differences between the mean ADC values for a prostate tumor with a Gleason score of 6 and one with a Gleason score of 7 (p = 0.0096) and for a prostate tumor with a Gleason score of 6 and one with a Gleason score of 8 (p = 0.0460) were significant. Comparison between the ADC and percentage of tumor on core biopsy showed a mean ADC decrease of 0.006 (range, 0.004-0.008 x 10(-3) mm(2)/s) for every 1% increase in tumor in the core biopsy specimen. CONCLUSION: DWI may help differentiate between low-risk (Gleason score, 6) and intermediate-risk (Gleason score, 7) prostate cancer and between low-risk (Gleason score, 6) and high-risk (Gleason score > 7) prostate cancer. There is an inverse relationship between the ADC and the percentage of tumor involvement on prostate core biopsies. PMID- 20308477 TI - MRI in lipid-lowering agent-associated myopathy: a retrospective review of 21 cases. AB - OBJECTIVE: The objective of our study was to identify disease-specific patterns of myopathic changes in patients with lipid-lowering agent (LLA)-associated myopathy using a dedicated MRI protocol. MATERIALS AND METHODS: Axial T1- and T2 weighted STIR images were obtained for the detection of lipomatosis and edema, respectively, of the thighs and legs. Information about patient age, sex, duration of dyslipidemia and of medication use, latency of symptom onset, maximum creatine kinase (CK) level, presence of myalgia and muscle weakness, and LLA or LLAs used was collected. RESULTS: Significant correlations resulted for the radiologic diagnosis of LLA-associated myopathy and maximum CK level; the presence of edema and maximum CK level; edema and weakness in the ventral thigh muscle group, thigh adductors, or deep dorsal muscle group of the legs; and lipomatosis and weakness of the deep dorsal muscle group of the legs and peroneal muscle group, respectively. CONCLUSION: MRI is a method that helps detect active pathologic processes in patients with suspected LLA-associated myopathy but does not reveal disease-specific patterns. PMID- 20308478 TI - Skeletal SPECT/CT of the peripheral extremities. AB - OBJECTIVE: Hybrid cameras that combine SPECT and helical CT can be used to correlate scintigraphic information with morphologic information in one imaging session. The purpose of this study was to investigate, in comparison with the value of scintigraphy and SPECT alone, the incremental diagnostic value of skeletal SPECT/CT in the care of patients with pain of the extremities. MATERIALS AND METHODS: Seventy-one patients without cancer who had pain in the extremities underwent three-phase bone scintigraphy and SPECT/CT of either the upper (n = 20) or the lower (n = 51) extremities. Planar scintigraphic and SPECT images and planar scintigraphic and SPECT/CT images were interpreted independently from each other. The findings were classified into the following diagnostic categories: normal, trauma, tumor, osteomyelitis, and osteoarthritis. RESULTS: Four patients had no abnormal bone metabolism or CT abnormality in the extremities. Among 34 lesions classified as osteoarthritis on planar and SPECT images, seven were reclassified as fracture and one as benign tumor at SPECT/CT. Of 15 lesions initially classified as osteomyelitis, four were diagnosed as osteoarthritis, four as fracture, and one as inflammation of the soft tissue only. Of eight diagnoses of fracture with the conventional approach, two were reclassified as osteomyelitis and two as osteoarthritis. In one of 10 patients with the initial diagnosis of a tumorlike lesion, the diagnosis was changed to trauma on the basis of SPECT/CT findings, and in another patient, the diagnosis was changed to osteoarthritis. Overall, SPECT/CT findings led to revision of the diagnostic category in the cases of 23 of 71 patients (p < 0.01). CONCLUSION: Compared with bone scintigraphy and SPECT, the use of SPECT/CT increases diagnostic accuracy in the evaluation of orthopedic disorders affecting the extremities. PMID- 20308479 TI - Superior vena cava obstruction evaluation with MDCT. AB - OBJECTIVE: The purpose of this article is to review the CT findings associated with superior vena cava obstruction and to illustrate collateral venous pathways bypassing the obstruction as shown on MDCT. CONCLUSION: Multiple collateral venous pathways can form to bypass an obstruction of the superior vena cava. With its ability to acquire near isotropic data, MDCT allows high-quality reformations and thus exquisitely displays these venous collaterals and has the potential to aid in planning therapy to bypass the obstruction. PMID- 20308480 TI - Ultrasound guiding device: suggestions for further improvements. PMID- 20308481 TI - CT distinction of interarterial and intraseptal courses of anomalous left coronary artery arising from inappropriate aortic sinus. PMID- 20308482 TI - Recognition of specific morphologic patterns for identifying benign thyroid nodules. PMID- 20308483 TI - Control and management of the radiation environment. PMID- 20308484 TI - Image gently: Ten steps you can take to optimize image quality and lower CT dose for pediatric patients. PMID- 20308485 TI - Embryo dose estimates in body CT. AB - OBJECTIVE: The purpose of this article is to develop a method for estimating embryo doses in CT. MATERIALS AND METHODS: Absorbed doses to the uterus (embryo) of a 70-kg woman were estimated using the ImPACT CT Patient Dosimetry Calculator. For a particular CT scan length, relative uterus doses and normalized plateau uterus doses were determined for a range of commercial CT scanners. Patient size characteristics were obtained from cross-sectional axial images of 100 consecutive patients (healthy women undergoing unenhanced pelvic CT examinations). For each patient, the diameter of a water cylinder with the same mass as the patient's pelvis was computed. Relative dose values were generated for cylinder diameters ranging from 16 to 36 cm at x-ray tube voltages between 80 and 140 kV. RESULTS: Values of relative uterus dose increased monotonically with increasing scan length, independently of scanner model, and reached a plateau for scan lengths greater than approximately 50 cm. The average normalized plateau uterus dose for all scanners was approximately 1.4 and showed interscanner differences of less than 10% for modern scanners operated at 120 kV. Normalized plateau doses show little dependence on the x-ray tube voltage used to perform the CT examination. Our results show that the uterus dose estimate in an abdominal or pelvis CT examination performed on a 70-kg patient is about 40% higher than the reported value of the volume CT dose index (CTDI(vol)). The pelvis of a 70-kg patient may be modeled as a water cylinder with a diameter of 28 cm and has an average anteroposterior dimension of 22 cm. For constant CT technique factors, embryo dose estimates for a 45-kg patient would be approximately 18% higher than those for a 70-kg patient, whereas the corresponding dose estimates in a 120-kg patient would be approximately 37% lower. CONCLUSION: Embryo doses can be estimated using relative uterus doses, normalized plateau uterus doses, and CTDI(vol) data with correction factors for patient size. PMID- 20308486 TI - Estimating effective dose for CT using dose-length product compared with using organ doses: consequences of adopting International Commission on Radiological Protection publication 103 or dual-energy scanning. AB - OBJECTIVE: The objective of our study was to compare dose-length product (DLP) based estimates of effective dose with organ dose-based calculations using tissue weighting factors from publication 103 of the International Commission on Radiological Protection (ICRP) or dual-energy CT protocols. MATERIALS AND METHODS: Using scanner- and energy-dependent organ dose coefficients, we calculated effective doses for CT examinations of the head, chest, coronary arteries, liver, and abdomen and pelvis using routine clinical single- or dual energy protocols and tissue-weighting factors published in 1991 in ICRP publication 60 and in 2007 in ICRP publication 103. Effective doses were also generated from the respective DLPs using published conversion coefficients that depend only on body region. For each examination type, the same volume CT dose index was used for single- and dual-energy scans. RESULTS: Effective doses calculated for CT examinations using organ dose estimates and ICRP 103 tissue weighting factors differed relative to ICRP 60 values by -39% (-0.5 mSv, head), 14% (1 mSv, chest), 36% (4 mSv, coronary artery), 4% (0.6 mSv, liver), and -7% ( 1 mSv, abdomen and pelvis). DLP-based estimates of effective dose, which were derived using ICRP 60-based conversion coefficients, were less than organ dose based estimates for ICRP 60 by 4% (head), 23% (chest), 37% (coronary artery), 12% (liver), and 19% (abdomen and pelvis) and for ICRP 103 by -34% (head), 37% (chest), 74% (coronary artery), 16% (liver), and 12% (abdomen and pelvis). All results were energy independent. CONCLUSION: These differences in estimates of effective dose suggest the need to reassess DLP to E conversion coefficients when adopting ICRP 103, particularly for scans over the breast. For the evaluated scanner, DLP to E conversion coefficients were energy independent, but ICRP 60 based conversion coefficients underestimated effective dose relative to organ dose-based calculations. PMID- 20308487 TI - How effective is effective dose as a predictor of radiation risk? AB - OBJECTIVE: This article discusses the relatively recent adoption of effective dose in medicine that allows comparison between different imaging techniques, and describes the principles, pitfalls, and potential value of effective dose. The medical community must use this information wisely, realizing that effective dose represents a generic estimate of risk from a given procedure for a generic model of the human body. CONCLUSION: Effective dose is not the risk for any one individual. Due to the inherent uncertainties and oversimplifications involved, effective dose should not be used for epidemiologic studies or for estimating population risks. PMID- 20308488 TI - Pseudohelical scan for the dose profile measurements of 160-mm-wide cone-beam MDCT. AB - OBJECTIVE: Our objective was to determine what the reasonable total phantom length should be for the measurements and determination of length equilibrium, specifically for the Aquilion ONE cone-beam MDCT system. MATERIALS AND METHODS: Radiation dose measurements of a 160-mm-wide cone-beam-MDCT scanner and its radiation dose profile require a different approach than the traditional or conventional method using thermoluminescent dosimeters or small ionization chambers, which have been suggested by some investigators. In order to obtain the radiation dose profile of a cone-beam MDCT, two key elements must be addressed: proper instrumentation for the detection of radiation beam and inclusion of the tails of the radiation dose profile. In this study, a small (2 x 2 x 0.3 mm) solid-state detector was used to measure the dose profile, which required the introduction of a stepping motor to pull the detector through the phantom. Inclusion of the tails of the radiation dose profile meant more than one standard CT dose index phantom would be required to encompass the dose profile tails as much as practically possible. In fact, at minimum, a total of five standard CT dose index (CTDI) phantoms would be required to ensure the entire dose profile is included and detected. RESULTS: In the case of Toshiba Aquilion ONE MDCT with the maximum beam width of 160 mm, the phantom length that is required for the radiation dose profile measurement should be at least 750 mm, or 5 standard CTDI body phantoms. Current CTDI measurements utilizing 150 mm or 350 mm phantom lengths significantly underestimate the total dose of wide cone-beam MDCT. CONCLUSION: The measurement method outlined in this study amounts to an introduction of a new CT dose profile measurement using a pseudohelical scan. PMID- 20308489 TI - Contrast material injection protocol with the dose adjusted to the body surface area for MDCT aortography. AB - OBJECTIVE: The objective of our study was to investigate the effect on aortic enhancement of contrast material volumes adjusted for a patient's body surface area (BSA) at CT angiography (CTA). SUBJECTS AND METHODS: A 64-MDCT scanner was used to perform CTA of the whole aorta in 89 patients (mean age, 68.7 years) with confirmed or suspected aortoiliac disease. The patients were divided into groups: a body weight (BW) group (n = 45) and a BSA (n = 44) group. The contrast dose was 360 mg I/kg BW in the BW group and 12,753 mg I/m(2) BSA in the BSA group. Because the average BW of Japanese adults is approximately 60 kg, the contrast dose in the two protocols was identical in patients weighing 60 kg. We compared aortic enhancement achieved with the two protocols using the two-tailed Student's t test, and we used the generalized linear model to analyze the effect of patient age, sex, and BW on aortic enhancement in each protocol group. RESULTS: The mean aortic enhancement in the BW and BSA groups was 324.2 and 311.7 HU, respectively; the difference was not significant (p = 0.26). In the BW group, BW had a statistically significant effect on aortic enhancement (p < 0.01), whereas neither patient age nor sex did (p = 0.08 and 0.07, respectively). In the BSA group, the age, sex, BW, and BW by sex had no statistically significant effect on aortic enhancement (p = 0.33, 023, 0.10, and 0.16, respectively). CONCLUSION: Under the BSA protocol, aortic enhancement tended to be consistent and adequate regardless of patient BW. PMID- 20308490 TI - What radiologists want to see: stack mode display in PowerPoint. AB - OBJECTIVE: The purpose of this article is to describe a stack mode viewer that is fully embeddable in PowerPoint and does not require external files. CONCLUSION: We developed a Web-based service named "RadViewer" that creates a Flash-based stack mode viewer and that is automatically embedded into PowerPoint. Features include mouse wheel and keyboard scrolling, zoom, cine loop, and brightness and contrast controls similar to those of a PACS workstation. Stack mode viewer created by RadViewer can be used in most radiology society meetings and conferences that use PowerPoint. PMID- 20308491 TI - Measurement of pulmonary circulation parameters using time-resolved MR angiography in patients after Ross procedure. AB - OBJECTIVE: The purposes of our study were to retrospectively evaluate the pulmonary circulation parameters of pulmonary transit time and pulmonary blood volume in patients after Ross procedures using time-resolved MR angiography and to investigate associations with right ventricular dysfunction in the same group of patients. MATERIALS AND METHODS: Sixteen patients who had undergone a Ross procedure (12 men, four women; mean age, 42.13 +/- 14.24 years; age range, 21-68 years) and 16 age- and sex-matched control patients (12 men, 4 women; mean age, 42.25 +/- 14.62 years; age range, 21-68 years) were evaluated using cardiac MRI and Argus postprocessing software. Right and left ventricular volumetric parameters, including ejection fraction, end-systolic volume, and end-diastolic volume, were measured from cine true fast imaging with steady-state precession images. Pulmonary circulation parameters, including pulmonary transit time, were measured using dynamic time-resolved MR angiography and pulmonary blood volume was calculated. Pulmonary circulation parameters were correlated with volumetric parameters. The results were statistically analyzed using the Mann-Whitney U test, paired-samples Student's t test, Pearson's correlation, and linear regression. RESULTS: Pulmonary circulation parameters were significantly prolonged in patients after the Ross procedure compared with control patients (p < 0.01). Strong correlations exist between pulmonary circulation parameters and right ventricular function, especially pulmonary transit time and right ventricular ejection fraction (R > 0.60, p < 0.001). CONCLUSION: Patients after undergoing the Ross procedure had prolonged pulmonary transit times compared with normal control patients; this and other pulmonary circulation parameters best correlate with worsened right ventricular ejection fraction and may be predictors of right ventricular dysfunction in this group of patients. PMID- 20308492 TI - Combined cardiac CT and MRI for the comprehensive workup of hemodynamically relevant coronary stenoses. AB - OBJECTIVE: The purpose of our study was to prospectively evaluate the accuracy of a comprehensive assessment of coronary artery disease (CAD) with prospectively ECG-gated coronary CT angiography (CTA) and perfusion-cardiac MRI for the detection of hemodynamically relevant coronary stenoses. SUBJECTS AND METHODS: Forty-seven consecutive patients underwent k-space and time broad-use linear acquisition speed-up technique accelerated perfusion-cardiac MRI at 1.5 T and dual-source coronary CTA. Catheter coronary angiography (CA), coronary CTA, and perfusion-cardiac MRI were all performed within a median time interval of 7.5 days. Detection of hemodynamically relevant stenoses by the combination of coronary CTA plus perfusion-cardiac MRI was compared with the combination of CA plus perfusion-cardiac MRI, the latter serving as the standard of reference. RESULTS: CA identified stenoses in 75 of 141 coronary arteries (53.2%) in 33 of 47 patients (70.2%). Cardiac MRI revealed perfusion defects in 30 of 47 patients (63.8%). Image quality of coronary CTA was diagnostic in 635 of 638 segments (99.5%). Coronary CTA revealed stenoses greater than 50% in 76 of 141 coronary arteries (53.9%) of 33 of 47 patients (70.2%). Sensitivity, specificity, negative and positive predictive value, and accuracy of coronary CTA and perfusion-cardiac MRI versus CA and perfusion-cardiac MRI for the detection of hemodynamically relevant stenoses were 96.7%, 100%, 94.4%, 100%, and 97.9%, respectively. CONCLUSION: The combination of coronary CTA and perfusion-cardiac MRI shows diagnostic performance comparable to that of CA and perfusion-cardiac MRI. Preliminary data suggest that coronary CTA may replace CA in the diagnosis of hemodynamically relevant CAD. PMID- 20308493 TI - Influence of applying nitroglycerin in whole-heart free-breathing 3D coronary MR angiography. AB - OBJECTIVE: The purpose of our study was to assess the impact of sublingual nitroglycerin (NTG) spray on free-breathing 3D whole-heart coronary MR angiography (MRA). SUBJECTS AND METHODS: We compared the timing parameters; measured the lumen diameter of the major coronary arteries; calculated coronary vasodilation, apparent signal-to-noise ratio (SNR), and apparent contrast-to noise ratio (CNR); and evaluated the image quality on pre- and post-NTG coronary MRA in 15 volunteers. Statistical analysis was performed with p value less than 0.05 considered significant. RESULTS: The mean trigger delay and optimal acquisition window were shortened significantly and the mean scanning time was prolonged statistically after NTG administration. There was no significant alteration in terms of apparent SNR and apparent CNR. The lumen diameters were significantly larger in coronary MRA post-NTG than in that of pre-NTG, with an average 25.35% +/- 6.51% (SD) increase, and the left circumflex coronary artery (LCX) had slightly lower vasodilation in comparison with the right coronary artery. Image quality scores of 53 (39.3%, 53/135) segments were increased and 15 segments (11.1%, 15/135) decreased after NTG administration, and the remaining 67 segments (49.6%, 67/135) were unchanged. CONCLUSION: In general, sublingual NTG is useful for improving visualization of the coronary artery lumen and alleviating the impact of artifact. However, several alterations and disadvantages should be taken into consideration in view of the disturbed assessment of vasodilatory response in the LCX and the impaired quality in a minority of segments after NTG administration. Further studies are needed to evaluate the effect of beta-blockade on eliminating the disadvantages of sublingual NTG. PMID- 20308494 TI - Effect of padding duration on radiation dose and image interpretation in prospectively ECG-triggered coronary CT angiography. AB - OBJECTIVE: Prospectively ECG-triggered coronary CT angiography images are acquired during a window in middiastole. Additional surrounding x-ray beam on time, or padding, can be variably set, and the increased padding results in additional available phases for analysis. The purpose of this study was to assess the effect of padding duration on image interpretability and its incident effect on radiation dose. SUBJECTS AND METHODS: We prospectively evaluated imaging of 886 patients undergoing consecutive prospectively ECG-triggered coronary CT angiographic examinations at three centers and compared the findings in patients stratified by padding duration. We assessed the effect of padding duration on image interpretability and radiation dose. RESULTS: The mean patient age was 56 +/- 12 years, and 58% of the patients were men. The median heart rate was 55 beats/min (interquartile range, 50-61 beats/min). Padding duration was 0, 1-99, and 100-150 milliseconds for 268, 482, and 136 patients, respectively, with no difference in image interpretability rate between groups (per patient, 98.8%, 97.3%, and 97.1%; per artery, 99.2%, 99.2%, and 99.1%). The groups differed in median radiation dose (2.3 mSv [interquartile range, 1.5-3.2 mSv]; 3.8 mSv [interquartile range, 2.3-4.7 mSv]; 5.5 mSv [interquartile range, 3.8-6.1 mSv]; p < 0.001). Independent of patient and scan parameters, increased padding was associated with greater radiation dose (45% increase per 100-millisecond increase in padding, p < 0.001). CONCLUSION: In a large multicenter study of coronary CT angiography of patients with excellent heart rate control, the use of minimal padding was associated with a substantial reduction in radiation dose with preserved image interpretability. Use of no or reduced padding should be considered in dose-reduction strategies. PMID- 20308495 TI - High-pitch dual-source CT angiography of the thoracic and abdominal aorta: is simultaneous coronary artery assessment possible? AB - OBJECTIVE: The purpose of this study was to prospectively evaluate the average heart rate and heart rate variability required for diagnostic imaging of the coronary arteries with high-pitch dual-source CT angiography of the thoracic and thoracoabdominal aorta. SUBJECTS AND METHODS: One hundred consecutively registered patients (82 men, 18 women; mean age, 68 +/- 13 years) underwent clinically indicated CT angiography of the thoracic (n = 33) and thoracoabdominal (n = 67) aorta with a dual-source 128-MDCT scanner in ECG-synchronized high-pitch (pitch, 3.2) data acquisition mode. No beta-blockers were administered. The image quality of the coronary arteries was graded on a 3-point scale by two independent blinded readers. The average heart rate and heart rate variability before data acquisition were noted. Effective radiation doses were calculated. RESULTS: Interobserver agreement on grade of image quality for the 1,414 coronary segments evaluated by both observers was good (kappa = 0.68). Diagnostic image quality was found for 1,375 of the 1,414 segments (97.2%) in 83 of 100 patients (83%). In 17% of the patients, image quality was nondiagnostic for at least one coronary artery segment. Average heart rate and heart rate variability (each p < 0.05) were significantly higher in patients with at least one nondiagnostic coronary segment compared with those without. All patients with an average heart rate less than 63 beats/min and heart rate variability less than 1.2 beats/min had diagnostic image quality in all coronary segments. Effective radiation doses were 2.3 +/- 0.3 mSv for thoracic and 4.4 +/- 0.5 mSv for thoracoabdominal CT angiography. The average scan times were 0.88 +/- 0.06 second for thoracic and 1.67 +/- 0.15 seconds for thoracoabdominal CT angiography. CONCLUSION: For patients with an average heart rate less than 63 beats/min and heart rate variability less than 1.2 beats/min, dual-source CT angiography of the thoracoabdominal aorta at a high pitch of 3.2 delivers diagnostic depiction of the coronary arteries at a low radiation dose. PMID- 20308496 TI - High-resolution double arterial phase hepatic MRI using adaptive 2D centric view ordering: initial clinical experience. AB - OBJECTIVE: The objective of our study was to evaluate a new 3D fast spoiled gradient-recalled echo (FSPGR) sequence referred to as modified liver acceleration volume acquisition (LAVA) for high-resolution gadolinium-enhanced dual arterial phase liver MRI and to determine the effect of this technique on the timing of the contrast bolus and lesion detection. MATERIALS AND METHODS: Gadolinium-enhanced dual arterial phase liver MRI was performed in 109 patients using a modified LAVA sequence that supports adaptive 2D centric view ordering, efficient 2D autocalibrated acceleration, and partial-Fourier to achieve faster scan times while maintaining the same slice thickness, resolution, and coverage as single-phase imaging. After a fixed 20-second scan delay, a modified LAVA acquisition required a single 24- to 26-second breath-hold for two arterial phases with 56-60 slices per pass. Images were reviewed for timing relative to liver enhancement, lesion conspicuity, and lesion detection. Liver lesion depiction was evaluated qualitatively and quantitatively. A control group of 109 patients underwent imaging using a single arterial phase 3D FSPGR sequence, which was also performed with a fixed 20-second scan delay. RESULTS: The single arterial phase images produced optimal timing in the middle or late arterial phase in 79 (72%) of the 109 control group patients compared with 99 (91%) of the 109 study group patients who underwent imaging using a dynamic modified LAVA dual arterial phase sequence. For the modified LAVA sequence, the first-pass images were obtained during the mid arterial phase in 34 patients (31%). The second-pass images were obtained during the mid arterial phase in 51 patients (47%) and late arterial phase in 26 patients (24%). Sixty-two patients had liver lesions showing greater conspicuity--on the first phase in 17 patients (27%) and second phase in 45 patients (73%). Hypovascular lesions were more conspicuous on second-phase images in 24 (86%) of 28 patients. Hypervascular lesions were more conspicuous on first-phase images in 13 patients (38%) and on second-phase images in 21 (62%) of 34 patients. The first-phase images detected 165 and 155 liver lesions, respectively, for two observers compared with 233 and 224 lesions on the second phase images, whereas the combined dual arterial phase images detected 256 and 248 hepatic lesions. CONCLUSION: High-resolution dual arterial phase 3D FSPGR MRI improves the timing of the arterial phase of liver enhancement and provides additional information for liver lesion detection. PMID- 20308497 TI - Diagnostic performance of CT in the detection of intestinal ischemia associated with small-bowel obstruction using maximal attenuation of region of interest. AB - OBJECTIVE: The purpose of this study was to assess the diagnostic performance of CT in the detection of intestinal ischemia associated with small-bowel obstruction using the maximal attenuation of a region of interest (ROI). MATERIALS AND METHODS: Abdominal CT scans of 60 patients with small-bowel obstruction were retrospectively reviewed. The reference standard of the clinicopathologic groups was classified into four categories: no bowel necrosis, mucosal-submucosal necrosis, superficial muscle necrosis, and transmural necrosis. The viability of the small bowel on CT was evaluated by visual assessment using five categories (i.e., definitely intestinal ischemia, probably intestinal ischemia, possibly intestinal ischemia, equivocal CT results, and no intestinal ischemia) and by measurement of the maximal attenuation of an ROI at selected obstructed small-bowel loops on contrast-enhanced and unenhanced CT scans. Diagnostic performances were evaluated by one-way analysis of variance and receiver operating characteristic (ROC) curve analysis. RESULTS: The sensitivity, specificity, positive and negative predictive values, and accuracy of visual assessment for intestinal ischemia were 91.7% (33/36), 66.7% (16/24), 80.5% (33/41), 84.2% (16/19), and 81.7% (49/60), respectively. The maximal attenuation of the ROIs on contrast-enhanced CT and the subtraction value between the maximal attenuation on contrast-enhanced CT and that on unenhanced CT scans at selected bowel were significantly different according to clinicopathologic group (p < 0.001). The area under the ROC curve of the maximal attenuation subtraction values between contrast-enhanced and unenhanced CT scans (0.995) was higher than that of visual assessment (0.908) for the detection of intestinal ischemia. CONCLUSION: The quantification of bowel wall enhancement using the maximal attenuation of an ROI was a reliable and useful method for the diagnosis of intestinal ischemia and showed good correlation with pathology results. PMID- 20308498 TI - Pilot study assessing differentiation of steatosis hepatis, hepatic iron overload, and combined disease using two-point dixon MRI at 3 T: in vitro and in vivo results of a 2D decomposition technique. AB - OBJECTIVE: The purpose of our study was to evaluate whether two-point Dixon MRI using a 2D decomposition technique facilitates metabolite differentiation between lipids and iron in standardized in vitro liver phantoms with in vivo patient validation and allows semiquantitative in vitro assessment of metabolites associated with steatosis, iron overload, and combined disease. MATERIALS AND METHODS: The acrylamide-based phantoms were made to reproduce the T1- and T2 weighted MRI appearances of physiologic hepatic parenchyma and hepatic steatosis iron overload by the admixture of triglycerides and ferumoxides. Combined disease was simulated using joint admixtures of triglycerides and ferumoxides at various concentrations. For phantom validation, 30 patients were included, of whom 10 had steatosis, 10 had iron overload, and 10 had no liver disease. For MRI an in phase/opposed-phase T1-weighted sequence with TR/TE(opposed-phase)/TE(in-phase) of 4.19/1.25/2.46 was used. Fat/water series were obtained by Dixon-based algorithms. In-phase and opposed-phase and fat/water ratios were calculated. Statistical cluster analysis assessed ratio pairs of physiologic liver, steatosis, iron overload, and combined disease in 2D metabolite discrimination plots. RESULTS: Statistical assessment proved that metabolite decomposition in phantoms simulating steatosis (1.77|0.22; in-phase/opposed-phase|fat/water ratios), iron overload (0.75|0.21), and healthy control subjects (1.09|0.05) formed three clusters with distinct ratio pairs. Patient validation for hepatic steatosis (3.29|0.51), iron overload (0.56|0.41), and normal control subjects (0.99|0.05) confirmed this clustering (p < 0.001). One-dimensional analysis assessing in vitro combined disease only with in-phase/opposed-phase ratios would have failed to characterize metabolites. The 2D analysis plotting in phase/opposed-phase and fat/water ratios (2.16|0.59) provided accurate semiquantitative metabolite decomposition (p < 0.001). CONCLUSION: MR Dixon imaging facilitates metabolite decomposition of intrahepatic lipids and iron using in vitro phantoms with in vivo patient validation. The proposed decomposition technique identified distinct in-phase/opposed-phase and fat/water ratios for in vitro steatosis, iron overload, and combined disease. PMID- 20308499 TI - Feline esophagus and gastroesophageal reflux. AB - OBJECTIVE: The purposes of this study were to reassess the relation between a feline esophagus (transient transverse esophageal folds) and gastroesophageal reflux (GER) and to determine whether a feline esophagus is observed more often during swallowing or during reflux of barium. MATERIALS AND METHODS: A computerized search of double-contrast esophagrams was performed to generate four equal groups of 56 patients with marked, moderate, mild, and no GER. The imaging findings were reviewed to determine the frequency of a feline esophagus in these groups and whether this sign was detected during swallowing or reflux of barium. The presence of a feline esophagus also was correlated with the presence of a hiatal hernia, reflux esophagitis, a peptic stricture, and esophageal dysmotility. RESULTS: A feline esophagus was detected in 20 of 224 patients (9%). It was detected during reflux of barium in 17 patients (85%), swallowing of barium in two patients (10%), and both in one patient (5%). GER was present in all 20 patients with a feline esophagus and in 148 of the 204 patients (73%) without a feline esophagus (p = 0.0068). A significant relation also was found between a feline esophagus and the presence of a hiatal hernia (p = 0.0116) but not between a feline esophagus and the presence of reflux esophagitis, a peptic stricture, or esophageal dysmotility. CONCLUSION: All patients with a feline esophagus at barium esophagography had associated GER. These transverse folds were observed mainly during reflux of barium from the stomach rather than during swallowing of barium. When a feline esophagus is detected during barium studies, the patient is extremely likely to have GER whether or not GER is seen at fluoroscopy. PMID- 20308500 TI - Hypervascular liver masses on contrast-enhanced ultrasound: the importance of washout. AB - OBJECTIVE: The objective of our study was to determine the role of negative enhancement (washout), its presence and timing, in the differential diagnosis of hypervascular liver masses on contrast-enhanced ultrasound. MATERIALS AND METHODS: One-hundred forty-six hypervascular liver lesions (mean size, 3.9 cm; range, 1.0-17.0 cm) were evaluated with contrast-enhanced ultrasound over a 6 month period. Seventy-four were benign (29 hemangiomas, 31 focal nodular hyperplasia [FNH] lesions, seven adenomas, five inflammatory lesions, two other) and 72, malignant (41 hepatocellular carcinomas [HCCs], 25 metastases, six other). Two independent reviewers retrospectively recorded the presence and timing of washout in the portal venous phase, observing until 4 minutes after injection, of a contrast agent (perflutren microspheres). Diagnoses were confirmed by histopathology (n = 68) or clinicoradiologic follow-up (n = 78). Timing of washout was compared between types of lesion using Fisher's exact test. RESULTS: Washout occurred in both benign (27/74, 36%) and malignant (70/72, 97%) lesions but was more frequently seen in malignancy (p < 0.001) (kappa = 0.91). Metastases showed more rapid washout than HCCs (p < 0.001): 20 of 25 metastases showed washout by 30 seconds after injection and 23 of 41 HCCs, later than 75 seconds. All malignant lesions without washout were HCCs (2/41). Among the benign lesions, all five inflammatory lesions showed rapid washout before 75 seconds and six of seven adenomas showed washout, mostly later than 75 seconds (5/6). Washout also occurred in hemangiomas (6/29) and FNH lesions (9/31), mostly later than 75 seconds after injection (12/15). CONCLUSION: Hypervascular malignant lesions show washout except infrequent cases of HCC. Rapid washout characterizes metastases, whereas HCCs show variable, often slow, washout. However, washout is not unique to malignancy and may be seen in benign lesions. PMID- 20308501 TI - Complementary roles of CT and endoscopic ultrasound in evaluating a pancreatic mass. AB - OBJECTIVE: The objectives of our study were to illustrate normal pancreatic anatomy using endoscopic ultrasound and to show the imaging findings of solid pancreatic masses on endoscopic ultrasound and CT. CONCLUSION: CT and endoscopic ultrasound have complementary roles in the diagnosis of solid pancreatic masses. PMID- 20308502 TI - Radiologic mimics of cirrhosis. AB - OBJECTIVE: The objective of this article is to provide a practical review of the conditions other than cirrhosis that can result in diffuse surface nodularity of the liver or portal hypertension. CONCLUSION: Conditions that can mimic cirrhosis on imaging include pseudocirrhosis of treated breast cancer metastases to the liver, fulminant hepatic failure, miliary metastases, sarcoidosis, schistosomiasis, congenital hepatic fibrosis, idiopathic portal hypertension, early primary biliary cirrhosis, chronic Budd-Chiari syndrome, chronic portal vein thrombosis, and nodular regenerative hyperplasia. PMID- 20308503 TI - Optimizing detectability of renal pathology with MDCT: protocols, pearls, and pitfalls. AB - OBJECTIVE: The purpose of this article is to review MDCT acquisition protocol parameters and interpretative practices for evaluating genitourinary lesions other than classic renal cell carcinoma, to optimize lesion detectability and accurately characterize pathologic abnormalities. CONCLUSION: With the goal of refining interpretative performance, this pictorial essay shows the patterns of conspicuity unique to each genitourinary pathologic abnormality, presents experience-based recommendations to improve detection and characterization using multiphasic MDCT, and describes pitfalls to be avoided. PMID- 20308504 TI - Masters of radiology panel discussion: role of communication in today's radiologic practices. PMID- 20308505 TI - Frequency of use of imaging tests in the diagnosis of pulmonary embolism: effects of physician specialty, patient characteristics, and region. AB - OBJECTIVE: The purpose of this study was to ascertain whether clinical practice in diagnosing pulmonary embolism is consistent with recommendations in the literature and to explore variations in practice across site of care (e.g., emergency department), physician and patient characteristics, and geographic location. MATERIALS AND METHODS: Medicare 5% research identifiable files were analyzed. The cases of patients with emergency department visits or inpatient stays for a diagnosis of pulmonary embolism or for symptoms related to pulmonary embolism (shortness of breath, chest pain, and syncope) were identified. We determined the number of patients who underwent each type of relevant imaging test and evaluated variations in the first non-chest-radiographic test by site of care and treating physician specialty. Using logistic regression, we studied variations in the use of common imaging tests, exploring variations associated with patient characteristics, physician specialty, site of care, and geographic location. RESULTS: For patients in whom pulmonary embolism might have been suspected, the most common tests were echocardiography (26% of the patients), CT or CT angiography of the chest (11%), cardiac perfusion study (6.9%), and duplex ultrasound (7.3%). For patients with an inpatient diagnosis of pulmonary embolism, the most common tests were chest CT or CT angiography (49%), duplex ultrasound (18%), echocardiography (10.9%), and ventilation-perfusion scintigraphy (10.9%). For patients for whom pulmonary embolism might have been suspected, many large variations were found in practice patterns among physician specialties and geographic locations. There were fewer variations among patients with the inpatient diagnosis of pulmonary embolism. CONCLUSION: Physician practice in the diagnosis of pulmonary embolism is broadly consistent with recommendations. However, variations by physician specialty and geographic location may be evidence of inappropriate imaging. PMID- 20308506 TI - The educational and career impact of using medical students for triaging off-hour diagnostic imaging requests at a major academic medical center. AB - OBJECTIVE: The purpose of this article is to evaluate the educational and career impact of using medical students for triaging off-hour diagnostic imaging requests at a major academic medical center. SUBJECTS AND METHODS: A survey of former and current medical students who participated in the Emergency Department Radiology Triage Program at the Yale University School of Medicine was conducted via e-mail. Results were reported using averages or percentages or both. RESULTS: Twenty-six (61.9%) of the 42 participants responded. Seventeen (65.4%) of the 26 respondents pursued an additional degree while in the program. The most important factor for joining was financial, with a mean importance of 4.0 on a scale of 1 (no importance) to 5 (most important). Eleven (42.3%) of the 26 respondents stated that their participation encouraged them to pursue a career in diagnostic radiology. Nine (34.6%) of the 26 respondents stated that the program had major or moderate importance on their specialty choice, whereas 20 of the 26 (76.9%) described the program as being of at least moderate help to their medical career. The most satisfying aspect of the program, on a scale of 1 (extremely dissatisfying) to 5 (extremely satisfying), was interacting with the junior radiology resident (mean rating, 4.5), whereas the least satisfying aspect was the Veterans Affairs triage component (mean rating, 2.9). CONCLUSION: The use of medical students for triaging off-hour diagnostic imaging requests has proven successful from an operational standpoint; it also appears to be favorably viewed concurrently and retrospectively by the growing cohort of students who have participated. PMID- 20308507 TI - Geographic variation in the utilization of noninvasive diagnostic imaging: national medicare data, 1998-2007. AB - OBJECTIVE: This study provides an overview of geographic variation in noninvasive diagnostic imaging utilization in the Medicare population over the period 1998 to 2007. MATERIALS AND METHODS: The Centers for Medicare and Medicaid Services Physician Supplier Procedure Summary Master Files for 1998-2007 were the primary data source for the study. Physician Supplier Procedure Summary Master Files are an aggregation of the complete Part B Medicare billing records for all 32-37 million fee-for-service beneficiaries and provide the total number of each type of procedure performed, categorized by geographic regions. For the 10 Centers for Medicare and Medicaid Services geographic regions, we calculated the overall noninvasive diagnostic imaging procedure utilization rate and the ratio of the highest to lowest region (a relative risk statistic) for each year of the study. For the first and last years of the study, we calculated these numbers for 28 noninvasive diagnostic imaging categories. RESULTS: In 2007, the Atlanta region had the highest utilization rate, with 4.60 procedures per capita, and Seattle had the lowest rate, with 2.99 procedures per capita. The relative risk was 1.54. Over the 10 years of the study, there was little change in the relative utilization rates of regions, and the relative risk ranged between 1.47 and 1.56. In 2007, bone densitometry showed the lowest regional relative risk (1.29), and cardiovascular PET showed the highest regional relative risk (70.2). Cardiovascular noninvasive diagnostic imaging and high-technology, high-cost noninvasive diagnostic imaging (e.g., MRI, PET, and nuclear medicine) showed high regional relative risk. CONCLUSION: Regional variation is substantial--about 50% higher in the highest regions than in the lowest regions--but is not huge. Regional variation is increasing slightly. Cardiovascular and high-technology procedures show the greatest regional variation. PMID- 20308508 TI - Radiologic malpractice litigation risk in Italy: an observational study over a 14 year period. AB - OBJECTIVE: The purpose of this study is to assess the risk of medical malpractice litigation for Italian radiologists, compared with the corresponding data in the literature. MATERIALS AND METHODS: The insurance claims of Italian radiologists over the 1993-2006 period were anonymously assessed and classified according to the cause of the claim. RESULTS: A total of 1,424 claims were filed during the examined period, with most claims being filed at a considerable time interval after the event (up to 10 years). The resulting incidence may be estimated as 44.2 cases per 1,000, meaning that 44% of Italian radiologists have received, or will receive, summons regarding their professional activity during the past 10 years. CONCLUSION: The risk of medical malpractice litigation for Italian radiologists is by now comparable to that for American radiologists. Comparison with previous data concerning the same study population shows that the diagnostic errors category has surpassed all other error categories (nondiagnostic errors) and that, within the diagnostic errors category, claims for allegedly missed cancer have surpassed claims for allegedly missed bone abnormalities. Among missed diagnosis claims, the maximum increase concerned mammograms. Strict adherence to radiologic standards and radiotherapy protocols may be a means of reducing the risk of legal action and obviating litigation. PMID- 20308509 TI - Favorable outcomes after sonographically guided intratendinous injection of hyperosmolar dextrose for chronic insertional and midportion achilles tendinosis. AB - OBJECTIVE: The objective of our study was to report on changes in the short-term sonographic appearance and 2-year follow-up for pain outcomes in a large patient population with chronic Achilles tendinosis who underwent sonographically guided dextrose injections. SUBJECTS AND METHODS: One hundred eight tendons (86 midportion and 22 insertional) from 99 patients experiencing pain for greater than 6 months at either the Achilles tendon insertion or midportion were included in the study. Gray-scale (5-12 and 7-15 MHz) and color Doppler sonography examinations preceded the injection procedure using a 27-gauge needle administering a net 25% dextrose-lidocaine solution intratendinously. Structural features of each tendon and presence of neovascularity were noted. Visual analog scale (VAS) items were recorded at baseline, posttest, and 28.6 months follow-up. RESULTS: A median of five (range, 1-13) injection consultations were needed for each patient, spaced 5.6 +/- 3.1 (SD) weeks apart. There was a significant improvement in pain scores for both midportion (rest: 34.1 +/- 27.7-3.3 +/- 7.4, activities of daily living (ADL): 50.2 +/- 25.6-9.5 +/- 16.2, and sport: 70.7 +/- 23.3-16.7 +/- 22.0) and insertional (rest: 33.0 +/- 26.5-2.7 +/- 6.0, ADL: 51.3 +/- 25.4-10.0 +/- 16.3, and sport: 69.6 +/- 24.5-17.7 +/- 29.1) patients from baseline to follow-up for all VAS items. There were reductions in the size and severity of hypoechoic regions and intratendinous tears and improvements in neovascularity. CONCLUSION: Dextrose injections appear to present a low-cost and safe treatment alternative with good long-term evidence for reducing pain from pathology at either the insertion or midportion of the Achilles tendon. PMID- 20308510 TI - Radiographic detection of hip and pelvic fractures in the emergency department. AB - OBJECTIVE: Our purpose was to evaluate the detection of hip and pelvic fractures with radiography in the emergency department. MATERIALS AND METHODS: All MR images of the lower extremity or pelvis ordered from July 2005 through June 2008 by the emergency department after the patient had undergone radiography were retrospectively reviewed in consensus by two musculoskeletal radiologists. All radiographs and MR images were reviewed in regard to patient age and sex, MRI protocol, site of fracture, fracture identification, other possible pain generators, and unexpected findings. Receiver operating characteristics analysis was performed on the findings. RESULTS: A total of 92 patients and 97 examinations were included. Our patient sample (77 women, 15 men; average age, 70.8 years; range, 19-94 years) had an elderly female bias. Sixty-five of the patients had a history of trauma. Thirteen patients (14%) with normal radiographic findings were found to have 23 fractures at MRI (six hip and 17 pelvic fractures). In 11 patients (12%) MRI showed no fracture after radiographic findings had suggested the presence of a fracture. In another 15 patients who had abnormal findings on radiographs, MRI depicted 12 additional pelvic fractures not identified on radiographs. In 43 of the 59 patients (73%) without MRI evidence of a fracture, the MRI findings suggested the presence of a potential pain generator, including muscle edema and tears, trochanteric bursitis, and hamstring tendinopathy. Receiver operating characteristics analysis for the detection of hip fractures with radiography showed an area under the curve of 0.74. CONCLUSION: Our study showed poor sensitivity of radiography in the evaluation of hip and pelvic pain in the emergency department. PMID- 20308511 TI - Diagnosis of proximal femoral insufficiency fractures in patients receiving bisphosphonate therapy. AB - OBJECTIVE: The purpose of this article is to describe the imaging features of proximal femoral insufficiency fractures in patients on long-term bisphosphonate therapy. CONCLUSION: The imaging findings of bisphosphonate-related femoral insufficiency fractures, which include a typical proximal diaphyseal location and transverse liner radiolucency through localized thickening of the lateral cortex, allow a specific diagnosis. PMID- 20308512 TI - The importance of sagittal 2D reconstruction in pelvic and sacral trauma: avoiding oversight of U-shaped fractures of the sacrum. AB - OBJECTIVE: The U-shaped sacral fracture can be overlooked without appropriate imaging. Radiographic and CT imaging of seven patients with U-shaped sacral fractures was reviewed. CONCLUSION: Although it is difficult to discern on anteroposterior radiographs and axial or coronal CT, the fracture is easily identifiable on CT images in the sagittal plane. We advocate reconstruction of CT images of the sacrum in the sagittal plane in trauma to prevent failure of identification. PMID- 20308513 TI - Dual-energy CT as a potential new diagnostic tool in the management of gout in the acute setting. AB - OBJECTIVE: Gout is the most common crystal deposition arthropathy currently diagnosed clinically and with arthrocentesis. Dual-energy CT is a promising new imaging technique offering potential new applications in a number of clinical areas. CONCLUSION: The ability of dual-energy CT to diagnose early gout and its use as a problem-solving tool is shown here. Diagnosis of subclinical gout could avert associated long-term complications, thereby reducing disease burden and improving overall quality of life. PMID- 20308514 TI - MR arthrography of the second and third metatarsophalangeal joints for the detection of tears of the plantar plate and joint capsule. AB - OBJECTIVE: Tears of the plantar plate and joint capsule of the metatarsophalangeal joint are underrecognized causes of lesser metatarsalgia. This study evaluated MR arthrography for evaluation of this condition in 45 metatarsophalangeal joints in 41 patients. CONCLUSION: Most metatarsophalangeal joint capsular tears occur at the distal lateral border of the plantar plate, often with injury of the adjacent interosseous tendon. Plantar plate tears are less common. MR arthrography of the metatarsophalangeal joint delineates capsular tears and associated abnormalities. PMID- 20308515 TI - Head and neck cancers on CT: preliminary study of treatment response assessment based on computerized volume analysis. AB - OBJECTIVE: The objective of our study was to investigate the feasibility of computerized segmentation of lesions on head and neck CT scans and evaluate its potential for estimating changes in tumor volume in response to treatment of head and neck cancers. MATERIALS AND METHODS: Twenty-six CT scans were retrospectively collected from the files of 13 patients with 35 head and neck lesions. The CT scans were obtained from an examination performed before treatment (pretreatment scan) and an examination performed after one cycle of chemotherapy (posttreatment scan). Thirteen lesions were primary site cancers and 22 were metastatic lymph nodes. An experienced radiologist (radiologist 1) marked the 35 lesions and outlined each lesion's 2D contour on the best slice on both the pre- and posttreatment scans. Full 3D contours were also manually extracted for the 13 primary tumors. Another experienced radiologist (radiologist 2) verified and modified, if necessary, all manually drawn 2D and 3D contours. An in-house developed computerized system performed 3D segmentation based on a level set model. RESULTS: The computer-estimated change in tumor volume and percentage change in tumor volume between the pre- and posttreatment scans achieved a high correlation (intraclass correlation coefficient [ICC] = 0.98 and 0.98, respectively) with the estimates from manual segmentation for the 13 primary tumors. The average error in estimating the percentage change in tumor volume by automatic segmentation relative to the radiologists' average error was -1.5% +/- 5.4% (SD). For the 35 lesions, the ICC between the automatic and manual estimates of change in pre- to posttreatment tumor area was 0.93 and of percentage change in pre- to posttreatment tumor area was 0.85. The average error in estimating the percentage change in tumor area by automatic segmentation was -3.2% +/- 15.3%. CONCLUSION: Preliminary results indicate that this computerized segmentation system can reliably estimate changes in tumor size on CT scans relative to radiologists' manual segmentation. This information can be used to calculate changes in tumor size on pre- and posttreatment scans to assess response to treatment. PMID- 20308516 TI - Medullary thyroid carcinoma: comparison with papillary thyroid carcinoma and application of current sonographic criteria. AB - OBJECTIVE: The aim of this study was to evaluate whether sonography can diagnose medullary thyroid carcinoma (MTC) as a malignant lesion using widely accepted sonographic criteria and to compare which sonographic findings of MTC are different from findings for papillary thyroid carcinoma (PTC). MATERIALS AND METHODS: The study included 42 patients (13 men and 29 women; mean age, 48 years) with 46 MTCs and 51 consecutive patients (10 men and 41 women; mean age, 48 years) with 55 PTCs that were confirmed at surgery. Two radiologists retrospectively determined the sonographic diagnoses according to malignant criteria (a taller-than-wide shape, spiculated margin, marked hypoechogenicity, and microcalcifications or macrocalcifications) and compared the sonographic findings of MTCs and PTCs. RESULTS: MTCs were diagnosed as malignant for 72% of cases by sonography, whereas PTCs were 87% malignant (p = 0.0511). Compared with PTCs, MTCs were larger (mean size, 2.3 +/- 1.5 cm vs 1.1 +/- 1.1 cm) (p = 0.001; odds ratio [OR], 3.84; 95% CI, 1.719-8.565), more frequently showed the presence of a cystic change (33% vs 4%) (p = 0.0226; OR, 0.10; 95% CI, 0.014-0.725), and more commonly showed homogeneous echotexture of the solid portion (59% vs 31%) (p = 0.0004; OR, 0.08; 95% CI, 0.019-0.321). MTCs tended to show an oval shape and circumscribed margin, but there was no statistical significance in multivariate analysis. There were no significant differences in echogenicity, presence, and type of calcification for MTCs and PTCs. CONCLUSION: Currently accepted sonographic criteria can be applied for a diagnosis of MTCs. MTCs differ from PTCs in size, presence of a cystic change, and echotexture. PMID- 20308517 TI - A practical MRI grading system for lumbar foraminal stenosis. AB - OBJECTIVE: This study aimed to evaluate the reproducibility of a new grading system for lumbar foraminal stenosis. MATERIALS AND METHODS: Four grades were developed for lumbar foraminal stenosis on the basis of sagittal MRI. Grade 0 refers to the absence of foraminal stenosis; grade 1 refers to mild foraminal stenosis showing perineural fat obliteration in the two opposing directions, vertical or transverse; grade 2 refers to moderate foraminal stenosis showing perineural fat obliteration in the four directions without morphologic change, both vertical and transverse directions; and grade 3 refers to severe foraminal stenosis showing nerve root collapse or morphologic change. A total of 576 foramina in 96 patients were analyzed (from L3-L4 to L5-S1). Two experienced radiologists independently assessed the sagittal MR images. Interobserver agreement between the two radiologists and intraobserver agreement by one reader were analyzed using kappa statistics. RESULTS: According to reader 1, grade 1 foraminal stenosis was found in 33 foramina, grade 2 in six, and grade 3 in seven. According to reader 2, grade 1 foraminal stenosis was found in 32 foramina, grade 2 in six, and grade 3 in eight. Interobserver agreement in the grading of foraminal stenosis between the two readers was found to be nearly perfect (kappa value: right L3-L4, 1.0; left L3-L4, 0.905; right L4-L5, 0.929; left L4-L5, 0.942; right L5-S1, 0.919; and left L5-S1, 0.909). In intraobserver agreement by reader 1, grade 1 foraminal stenosis was found in 34 foramina, grade 2 in eight, and grade 3 in seven. Intraobserver agreement in the grading of foraminal stenosis was also found to be nearly perfect (kappa value: right L3-L4, 0.883; left L3-L4, 1.00; right L4-L5, 0.957; left L4-L5, 0.885; right L5-S1, 0.800; and left L5-S1, 0.905). CONCLUSION: The new grading system for foraminal stenosis of the lumbar spine showed nearly perfect interobserver and intraobserver agreement and would be helpful for clinical study and routine practice. PMID- 20308518 TI - Imaging presentation of venous thrombosis in patients with cancer. AB - OBJECTIVE: The purpose of this article is to review the imaging of venous thrombosis in patients with cancer. CONCLUSION: Multiple imaging techniques have the capacity to display thrombosis accurately. The optimal choice is dictated by the location and duration of symptoms and by the availability of imaging techniques. Peripheral and superficial thrombi are best managed with ultrasound, whereas central thrombi require CT or MRI. If CT and MRI are contraindicated, flow studies are appropriate. FDG PET/CT appropriately shows venous thrombosis and might play a prominent role in the future. PMID- 20308519 TI - MR spectroscopic evaluation of psychomotor delay of unknown cause in children. AB - OBJECTIVE: The aim of this study was to use MR spectroscopy to determine whether the brain metabolism of children with psychomotor delay of unknown cause differs from that of children without psychomotor delay. SUBJECTS AND METHODS: Twenty children (10 girls, 10 boys; mean age, 8.65 years; range, 4-15 years) with psychomotor delay and 19 children without psychomotor delay who served as controls (nine girls, 10 boys; mean age, 8.79 years; range, 6-13 years) were evaluated with multivoxel MR spectroscopy of the brain. The Stanford-Binet test and Wechsler Intelligence Scale for Children-Revised were used to evaluate developmental quotient. Psychomotor delay was assessed as severe (developmental quotient, < 50), moderate (developmental quotient, 50-75) and mild (developmental quotient, > 75). The controls had a developmental quotient greater than 95. Spectra were acquired from eight specific voxels at the bilateral parasagittal frontal and parietal gray matter and the bilateral frontal and parietal white matter at the level of the centrum semiovale. The ratios of N-acetylaspartate (NAA) to choline (Cho), NAA to creatine (Cr), and choline to creatine were determined. RESULTS: Thirteen children had minor and seven children had moderate psychomotor delay. In the psychomotor delay group, the right frontal white matter NAA/Cho, NAA/Cr, and Cho/Cr ratios were 1.45 +/- 0.18, 1.95 +/- 0.33, and 1.36 +/ 0.27; in the control group the ratios were 1.46 +/- 0.23, 2.04 +/- 0.33, and 1.41 +/- 0.19. The ratios for the left frontal lobe white matter were 1.34 +/- 0.21, 2.01 +/- 0.33, and 1.55 +/- 0.26 in the psychomotor delay group and 1.42 +/ 0.15, 2.17 +/- 0.34, and 1.53 +/- 0.25 in the control group. The ratios for the right parietal lobe white matter were 1.80 +/- 0.38, 2.04 +/- 0.43, and 1.18 +/- 0.35 in the psychomotor delay group and 1.89 +/- 0.31, 2.16 +/- 0.30, and 1.17 +/ 0.23 in the control group. The left parietal lobe white matter ratios were 1.66 +/- 0.36, 2.08 +/- 0.35, and 1.35 +/- 0.29 in the psychomotor delay group and 1.81 +/- 0.29, 2.17 +/- 0.35, and 1.22 +/- 0.26 in the control group. CONCLUSION: Metabolite distribution varied with brain region in children with and those without psychomotor delay. No significant difference was found between the brain metabolite ratios of children with psychomotor delay of unknown cause and those of age-matched children without psychomotor delay. PMID- 20308520 TI - Assessing early vascular changes and treatment response after laser-induced thermotherapy of pulmonary metastases with perfusion CT: initial experience. AB - OBJECTIVE: The objective of our study was to use perfusion CT to prospectively monitor early vascular changes in tumor perfusion of pulmonary metastases after laser-induced thermotherapy (LITT) and to determine whether any of the perfusion parameters would predict technical success after therapy. SUBJECTS AND METHODS: Twelve patients with histologically proven pulmonary metastases undergoing LITT were enrolled prospectively in this study. Perfusion CT was performed before treatment, 1 day after treatment, and 4-6 weeks after therapy, and tumor blood flow, tumor blood volume (TBV), mean transit time (MTT), and permeability of the capillary wall surface (capillary permeability-surface product) in 22 pulmonary metastases were calculated. Perfusion parameters at baseline and after LITT were compared. Measurement of tumor diameter on long-term follow-up CT was the gold standard with which perfusion CT results were compared for local control. RESULTS: Median tumor blood flow, TBV, and capillary permeability-surface product had decreased significantly from baseline by 43%, 61%, and 73%, respectively, 1 day after LITT. Perfusion parameters obtained 4-6 weeks after treatment had not changed significantly compared with those obtained 1 day after therapy. There seems to be a good correlation between changes in perfusion CT parameters 1 day after therapy and local outcome, according to the Response Evaluation Criteria in Solid Tumors (RECIST), 1 year after therapy. CONCLUSION: Perfusion CT of pulmonary metastases has potential in the assessment of early vascular changes that result from LITT and predicting technical success immediately after treatment. Tumors with perfusion measurements that had not changed after therapy indicated progressive disease. PMID- 20308521 TI - Chemoembolization of the left inferior phrenic artery in patients with hepatocellular carcinoma: 9-year single-center experience. AB - OBJECTIVE: The purpose of this study was to evaluate retrospectively the radiologic findings and imaging response of hepatocellular carcinoma supplied by the left inferior phrenic artery. MATERIALS AND METHODS: From January 2000 through December 2008, chemoembolization of the left inferior phrenic artery was performed on 152 patients (123 men, 29 women; mean age, 55.8 years) with hepatocellular carcinoma. The CT scans and digital subtraction angiograms of these patients were retrospectively reviewed in consensus by two investigators, who evaluated tumor location, tumor-feeding vessels, origin of the left inferior phrenic artery, technical success of chemoembolization, complications, and tumor response. Tumor response was assessed on the basis of the criteria of the European Association for the Study of the Liver. RESULTS: Tumors supplied by the left inferior phrenic artery were located in Couinaud segment 2/3 (n = 100), segment 4 (n = 45), and other segments (n = 7). The most common tumor-feeding vessel was the anteromedial limb of the left inferior phrenic artery (n = 82) followed by the lateral limb (n = 40) and the anterior limb (n = 30). Selective chemoembolization via the left inferior phrenic artery was achieved in 58 of the patients (38%). Complete or partial response as detected on first follow-up CT images (mean follow-up time, 2.5 months) was achieved by 30 patients. In 33 patients in whom the tumor was supplied exclusively by the left inferior phrenic artery, the tumor response was more favorable in patients who underwent selective than in those who underwent nonselective chemoembolization via the left inferior phrenic artery (p = 0.028). CONCLUSION: Selective chemoembolization via the left inferior phrenic artery is possible and results in good response of tumors supplied exclusively by the left inferior phrenic artery. PMID- 20308522 TI - Fluoroscopically guided balloon dilation for pharyngoesophageal stricture after radiation therapy in patients with head and neck cancer. AB - OBJECTIVE: The purpose of this article is to assess the safety and long-term efficacy of fluoroscopically guided balloon dilation for pharyngoesophageal strictures after radiation therapy in patients with head and neck cancers. MATERIALS AND METHODS: From April 1997 to February 2009, fluoroscopically guided balloon dilation was performed in 17 patients with pharyngoesophageal strictures caused by radiation therapy. Technical success, clinical success (decrease of at least one grade in dysphagia score and good contrast passage on 1-month follow-up esophagogram), recurrence of dysphagia, and complications related to the procedure were retrospectively evaluated. RESULTS: All 17 patients underwent 41 balloon dilation procedures, with each patient undergoing one to seven procedures (mean, 2.4 procedures). The technical success rate was 100%, and clinical success was achieved in 64.7% (11/17) of the patients. Five patients (29.4%) showed no recurrence of dysphagia after one session of balloon dilation. Of 12 patients (70.6%) with recurrence of dysphagia, 10 underwent repeat balloon dilation and two underwent gastrostomy after the first session of balloon dilation. The maximum balloon diameters were 15 mm (n = 22), 20 mm (n = 16), and 25 mm (n = 3). As minor complications, three cases of type 1 esophageal rupture occurred in two patients (11.8%). There were no major complications. CONCLUSION: Although the recurrence rate was high with repeat balloon dilation, fluoroscopically guided balloon dilation seems to be a simple and safe primary treatment technique for pharyngoesophageal stricture due to radiation therapy in patients with head and neck cancer. PMID- 20308523 TI - Benign predominantly solid thyroid nodules: prospective study of efficacy of sonographically guided radiofrequency ablation versus control condition. AB - OBJECTIVE: The purpose of this study was to evaluate the efficacy of radiofrequency ablation of benign predominantly solid thyroid nodules by comparing the findings in treatment and control groups. SUBJECTS AND METHODS: Thirty patients with normal thyroid function, each with a benign predominantly (> 50%) solid thyroid nodule causing pressure symptoms or cosmetic problems, were assigned to a control group (n = 15) or to a group undergoing a single session of radiofrequency ablation (n = 15). Thyroid nodule volume, thyroid function, pressure symptoms, and cosmetic concerns were evaluated before treatment and during follow-up. Sonographically guided radiofrequency ablation was performed with an internally cooled electrode (1-cm active tip) with an output power of 30 80 W. RESULTS: The control group had no resolution of symptoms or cosmetic problems. The mean nodule volume increased slightly after 6 months but without statistical significance (p = 0.46). In the radiofrequency ablation group, the mean symptom score (p = 0.001) and cosmetic grade (p = 0.001) improved significantly. Mean nodule volume decreased significantly from 7.5 +/- 4.9 mL (range, 1.7-20.0 mL) to 1.3 +/- 0.8 mL (range, 0.2-2.6 mL) 6 months after radiofrequency ablation (p = 0.001). There were no major complications of ablation. CONCLUSION: This study confirmed that radiofrequency ablation is effective for reducing nodule volume and relieving nodule-related clinical problems and that an effect due to spontaneous nodule reduction can be excluded owing to the results of the comparison with a similar control group. PMID- 20308524 TI - Radial scars without atypia diagnosed at imaging-guided needle biopsy: how often is associated malignancy found at subsequent surgical excision, and do mammography and sonography predict which lesions are malignant? AB - OBJECTIVE: The purposes of our study were to evaluate the surgical outcome of cases of radial scar without atypia diagnosed at imaging-guided percutaneous needle biopsy and to determine whether the mammographic and sonographic features are able to predict which lesions will be upgraded to malignancy at surgical excision. MATERIALS AND METHODS: The records of 4,458 consecutive imaging-guided biopsies were retrospectively reviewed. Surgical excision results were available in 62 cases in which radial scar was the highest-risk lesion at stereotactically guided or sonographically guided biopsy. The mammographic and sonographic images and surgical findings were reviewed. The underestimation rate of malignancy of percutaneous biopsy was calculated. Differences in mammographic and sonographic appearances between radial scars with and without associated malignancy were evaluated using the Fisher's exact test. RESULTS: The percutaneous malignancy underestimation rate was 8% (5/62): 9% (4/43) for sonography guided 14-gauge biopsies and 5% (1/19) for stereotactically guided 11-gauge vacuum-assisted biopsies (p = 1.000). Mammographic and sonographic appearances were not significantly different between radial scars with and those without associated malignancy. CONCLUSION: A percutaneous diagnosis of a radial scar does not exclude associated malignancy at surgical excision. Mammographic and sonographic features of a lesion diagnosed as a radial scar at percutaneous imaging-guided biopsy do not predict which lesions will have associated malignancy at surgery. Therefore, all patients with percutaneous diagnosis of a radial scar should undergo surgical excision regardless of mammographic and sonographic appearances, until further criteria can be determined. PMID- 20308526 TI - Multimodality imaging of triple receptor-negative tumors with mammography, ultrasound, and MRI. AB - OBJECTIVE: We retrospectively reviewed imaging findings for 44 patients with triple receptor-negative breast carcinomas on mammography, sonography, and MRI to determine the imaging characteristics of triple receptor-negative cancers that may improve diagnosis at the time of presentation. CONCLUSION: Despite their large size at presentation, triple receptor-negative cancers may be occult on mammography or sonography and frequently have benign or indeterminate features. MRI identified all triple receptor-negative cancers and showed features that had a high positive predictive value for malignancy. PMID- 20308525 TI - Recommendation for short-interval follow-up examinations after a probably benign assessment: is clinical practice consistent with BI-RADS guidance? AB - OBJECTIVE: American College of Radiology BI-RADS guidance suggests that women with a probably benign finding on mammography receive a management recommendation for short-interval follow-up; historically, radiologists in community practice have not consistently linked this assessment with short-interval follow-up. We evaluated predictors of discordance between probably benign assessments and short interval follow-up recommendations. MATERIALS AND METHODS: We linked data on 196 radiologists who completed a survey on demographic and practice patterns to 15,515 diagnostic mammograms they interpreted with probably benign assessments between 2001 and 2006. Patient characteristics were collected at the time of the mammography. Using logistic regression, we examined whether patient and radiologist characteristics were associated with the odds of short-interval follow-up recommendations (relative to a recommendation for normal follow-up, additional imaging evaluation, or biopsy or surgical consultation). RESULTS: Overall, 90.9% of mammograms with probably benign findings were recommended for short-interval follow-up; 4.3% were recommended for normal follow-up, 3.0% for additional imaging, and 1.8% for biopsy or surgical consultation. Women with probably benign findings were less likely to receive a short-interval follow-up recommendation if they had extremely dense breasts versus almost entirely fatty breasts (odds ratio [OR], 0.61; 95% CI, 0.39-0.96) or had a breast lump versus no symptoms (OR, 0.55; 95% CI, 0.38-78). Radiologists were less likely to recommend short-interval follow-up if they had >/= 20 years of experience versus < 10 years of experience (OR, 0.57; 95% CI, 0.36-0.90) but more likely if they practiced primarily at an academic medical center versus other institutions (OR, 2.66; 95% CI, 1.14-6.21). CONCLUSION: In contrast to older studies, the majority of probably benign assessments are now recommended for short-interval follow-up, but the probability of short-interval follow-up recommendations varies by patient and radiologist characteristics. PMID- 20308527 TI - Regulation of androgen-responsive transcription by the chromatin remodeling factor CHD8. AB - The androgen receptor (AR) mediates the effect of androgens through its transcriptional function during both normal prostate development and in the emergence and progression of prostate cancer. AR is known to assemble coactivator complexes at target promoters to facilitate transcriptional activation in response to androgens. Here we identify the ATP-dependent chromatin remodeling factor chromodomain helicase DNA-binding protein 8 (CHD8) as a novel coregulator of androgen-responsive transcription. We demonstrate that CHD8 directly associates with AR and that CHD8 and AR simultaneously localize to the TMPRSS2 enhancer after androgen treatment. In the LNCaP cell line, reduction of CHD8 levels by small interfering RNA treatment severely diminishes androgen-dependent activation of the TMPRSS2 gene. We demonstrate that the recruitment of AR to the TMPRSS2 promoter in response to androgen treatment requires CHD8. Finally, CHD8 facilitates androgen-stimulated proliferation of LNCaP cells, emphasizing the physiological importance of CHD8. Taken together, we present evidence of a functional role for CHD8 in AR-mediated transcriptional regulation of target genes. PMID- 20308528 TI - Aldose reductase regulates vascular smooth muscle cell proliferation by modulating G1/S phase transition of cell cycle. AB - Abnormal proliferation of vascular smooth muscle cells (VSMC) is a key feature of development of cardiovascular complications, atherosclerosis, and restenosis. Patients with diabetes have higher risk for restenosis after coronary angioplasty than nondiabetic patients due to hyperglycemia-induced release of cytokines such as TNF-alpha. However, the molecular mechanisms regulating VSMC proliferation remain unclear. Herein, we report that inhibition of the polyol pathway enzyme aldose reductase (AR) prevents high glucose (HG)- and/or TNF-alpha-induced VSMC proliferation by accumulating cells at the G1 phase of the cell cycle. Treatment of VSMC with AR inhibitor sorbinil prevented HG- as well as TNF-alpha-induced phosphorylation of retinoblastoma protein and activation of E2F-1. Inhibition of AR also prevented HG- and TNF-alpha-induced phosphorylation of cyclin-dependent kinase (cdk)-2 and expression of G1/S transition regulatory proteins such as cyclin D1, cyclin E, cdk-4, c-myc, and proliferative cell nuclear antigen. More importantly, inhibition of AR prevented the increased expression of E2F-1 and proliferative cell nuclear antigen in diabetic rat aorta. Treatment of VSMC with the most abundant and toxic lipid aldehyde 4-hydroxy-trans-2-nonenal (HNE) or its glutathione conjugate [glutathionyl (GS)-HNE] or AR-catalyzed product of GS-HNE, GS-1,4-dihydroxynonane, resulted in increased E2F-1 expression. Inhibition of AR prevented HNE- or GS-HNE-induced but not GS-1,4-dihydroxynonane-induced up regulation of E2F-1. Collectively, these results show that AR could regulate HG- and TNF-alpha-induced VSMC proliferation by altering the activation of G1/S-phase proteins such as E2F-1, cdks, and cyclins. Thus, inhibition of AR may be a useful therapeutic approach in preventing vascular complications. PMID- 20308529 TI - The nuclear receptor cofactor receptor-interacting protein 140 is a positive regulator of amphiregulin expression and cumulus cell-oocyte complex expansion in the mouse ovary. AB - The nuclear receptor cofactor receptor-interacting protein 140 (RIP140) is essential for cumulus cell-oocyte complex (COC) expansion, follicular rupture, and oocyte release during ovulation. The expression of many genes necessary for COC expansion is impaired in the absence of RIP140, but the studies herein document that their expression can be restored and COC expansion rescued by treatment with the epidermal growth factor (EGF)-like factor amphiregulin (AREG) both in vitro and in vivo. We demonstrate by several approaches that RIP140 is required for the expression of the EGF-like factors in granulosa cells, but the dependence of genes involved in cumulus expansion, including Ptgs2 Has2, Tnfaip6, and Ptx3, is indirect because they are induced by AREG. Treatment of granulosa cells with forskolin to mimic the effects of LH increases AREG promoter activity in a RIP140-dependent manner that 1) requires an intact cAMP response element in the proximal promoter region of the Areg gene and 2) involves its actions as a coactivator for cAMP response element-binding protein/c-Jun transcription factors. Although human chorionic gonadotropin and AREG coadministration is sufficient to restore ovulation fully in RIP140 heterozygous mice in vivo, both follicular rupture and ovulation remain impaired in the RIP140 null mice. Thus, we conclude that although the level of RIP140 expression in the ovary is a crucial factor required for the transient expression of EGF-like factors necessary for cumulus expansion, it also plays a role in other signaling pathways that induce follicular rupture. PMID- 20308530 TI - Identification, localization, and function of a novel avian hypothalamic neuropeptide, 26RFa, and its cognate receptor, G protein-coupled receptor-103. AB - Several neuropeptides with the C-terminal RFamide sequence have been identified in the hypothalamus of a variety of vertebrates. Among the RFamide peptide groups, however, only LPXRFamide peptides, including gonadotropin-inhibitory hormone, have been characterized in the avian brain. In the present study, we sought for the presence of other RFamide peptides in the avian hypothalamus. We identified a cDNA encoding an RFamide peptide orthologous to 26RFa (also referred to as QRFP) in the hypothalamus of the Japanese quail. The deduced quail 26RFa precursor consisted of 120-amino-acid residues, encoding one RFamide peptide with 27 amino acids. This RFamide peptide was flanked at the N terminus by a dibasic amino acid cleavage site and at the C terminus by a glycine amidation signal. Quantitative RT-PCR analysis demonstrated specific expression of quail 26RFa mRNA in the diencephalon including the hypothalamus. Furthermore, mass spectrometry analysis revealed the presence of a peptide exhibiting the mass of mature 26RFa, indicating that the peptide is actually produced from the precursor in the diencephalon. 26RFa-producing cell bodies were localized in the anterior hypothalamic nucleus in the brain. Synthetic 26RFa increased intracellular Ca(2+) concentration in HEK293T cells transfected with the chicken G protein-coupled receptor GPR103. Intracerebroventricular injection of 26RFa in broiler chicks stimulated feeding behavior. These data provide the first evidence for the occurrence of the peptide 26RFa in the avian hypothalamus and indicate that this peptide exerts orexigenic activity. PMID- 20308531 TI - The effect of relaxin on cell proliferation in mouse cervix requires estrogen receptor {alpha} binding to estrogen response elements in stromal cells. AB - The study objective was to determine whether stromal and/or epithelial estrogen receptor-alpha (ERalpha) is required for relaxin to promote proliferation of stromal and epithelial cells in the mouse cervix. Four types of tissue recombinants were prepared with cervical stroma (St) and epithelium (Ep) from wild-type (wt) and ERalpha knockout (ko) mice: wt-St+wt-Ep, wt-St+ko-Ep, ko-St+wt Ep and ko-St+ko-Ep. Tissue recombinants were grafted under the renal capsule of syngeneic female mice. After 3 wk of transplant growth, hosts were ovariectomized and fitted with silicon implants containing 17beta-estradiol (treatment d 1). Animals were injected sc with relaxin or vehicle PBS at 6-h intervals from 0600 h on d 8 through 0600 h on d 10. To evaluate cell proliferation, 5-bromo-2' deoxyuridine was injected sc 10 h before tissue recombinants were collected at 1000 h on d 10. Relaxin promoted marked proliferation of both epithelial and stromal cells in tissue recombinants containing wt St (P < 0.001) but far lower proliferation in recombinants prepared with ko St, regardless of whether Ep was derived from wt or ko mice. An additional experiment using mice expressing wt ERalpha, a mutant of ERalpha that selectively lacks classical signaling through estrogen response element binding, or no ERalpha demonstrated that ERalpha must bind to an estrogen response element to enable relaxin's proliferative effects. In conclusion, this study shows that ERalpha-expressing cells in St, using a classical signaling pathway, are necessary for relaxin to promote marked proliferation in both stromal and epithelial cells of the mouse cervix. PMID- 20308532 TI - The action of leptin on appetite-regulating cells in the ovine hypothalamus: demonstration of direct action in the absence of the arcuate nucleus. AB - It is widely accepted that leptin acts on first-order neurons in the arcuate nucleus (ARC) with information then relayed to other hypothalamic centers. However, the extent to which leptin mediates its central actions solely, or even primarily, via this route is unclear. We used a model of hypothalamo-pituitary disconnection (HPD) to determine whether leptin action on appetite-regulating systems requires the ARC. This surgical preparation eliminates the ARC. We measured effects of iv leptin to activate hypothalamic neurons (Fos labeling). In ARC-intact animals, leptin increased the percentage of Fos-positive melanocortin neurons and reduced percentages of Fos-positive neuropeptide Y neurons compared with saline-treated animals. HPD itself increased Fos labeling in the lateral hypothalamic area (LHA). Leptin influenced Fos labeling in the dorsomedial nucleus (DMH), ventromedial nucleus, and paraventricular nucleus (PVN) in HPD and normal animals, with effects on particular cell types varying. In the LHA and DMH, leptin decreased orexin cell activation in HPD and ARC-intact sheep. HPD abolished leptin-induced expression of Fos in melanin-concentrating hormone cells in the LHA and in CRH cells in the PVN. In contrast, HPD accentuated activation in oxytocin neurons. Our data from sheep with lesions encompassing the ARC do not suggest a primacy of action of leptin in this nucleus. We demonstrate that first order to second order signaling may not represent the predominant means by which leptin acts in the brain to generate integrated responses. We provide evidence that leptin exerts direct action on cells of the DMH, ventromedial nucleus, and PVN. PMID- 20308533 TI - Studies in zebrafish reveal unusual cellular expression patterns of gonadotropin receptor messenger ribonucleic acids in the testis and unexpected functional differentiation of the gonadotropins. AB - This study aimed to improve, using the zebrafish model, our understanding of the distinct roles of pituitary gonadotropins FSH and LH in regulating testis functions in teleost fish. We report, for the first time in a vertebrate species, that zebrafish Leydig cells as well as Sertoli cells express the mRNAs for both gonadotropin receptors (fshr and lhcgr). Although Leydig cell fshr expression has been reported in other piscine species and may be a common feature of teleost fish, Sertoli cell lhcgr expression has not been reported previously and might be related to the undifferentiated gonochoristic mode of gonadal sex differentiation in zebrafish. Both recombinant zebrafish (rzf) gonadotropins (i.e. rzfLH and rzfFSH) stimulated androgen release in vitro and in vivo, with rzfFSH being significantly more potent than rzfLH. Forskolin-induced adenylate cyclase activation mimicked, whereas the protein kinase A inhibitor H-89 significantly reduced, the gonadotropin-stimulated androgen release. Therefore, we conclude that both FSH receptor and LH/choriogonadotropin receptor signaling are predominantly mediated through the cAMP/protein kinase A pathway to promote steroid production. Despite this similarity, other downstream mechanisms seem to differ. For example, rzfFSH up-regulated the testicular mRNA levels of a number of steroidogenesis-related genes both in vitro and in vivo, whereas rzfLH or human chorionic gonadotropin did not. Although not fully understood at present, these differences could explain the capacity of FSH to support both steroidogenesis and spermatogenesis on a long-term basis, whereas LH-stimulated steroidogenesis might be a more acute process, possibly restricted to periods during which peak steroid levels are required. PMID- 20308534 TI - Tumor-infiltrating lymphocytes and mitotic index in metastatic melanoma as predictors of patient survival. PMID- 20308535 TI - Steady-state cross-presentation of OVA is mannose receptor-dependent but inhibitable by collagen fragments. PMID- 20308536 TI - Short N-terminal sequences package proteins into bacterial microcompartments. AB - Hundreds of bacterial species produce proteinaceous microcompartments (MCPs) that act as simple organelles by confining the enzymes of metabolic pathways that have toxic or volatile intermediates. A fundamental unanswered question about bacterial MCPs is how enzymes are packaged within the protein shell that forms their outer surface. Here, we report that a short N-terminal peptide is necessary and sufficient for packaging enzymes into the lumen of an MCP involved in B(12) dependent 1,2-propanediol utilization (Pdu MCP). Deletion of 10 or 14 amino acids from the N terminus of the propionaldehyde dehydrogenase (PduP) enzyme, which is normally found within the Pdu MCP, substantially impaired packaging, with minimal effects on its enzymatic activity. Fusion of the 18 N-terminal amino acids from PduP to GFP, GST, or maltose-binding protein resulted in their encapsulation within MCPs. Bioinformatic analyses revealed N-terminal extensions in two additional Pdu proteins and three proteins from two unrelated MCPs, suggesting that N-terminal peptides may be used to package proteins into diverse MCPs. The potential uses of MCP assembly principles in nature and in biotechnology are discussed. PMID- 20308537 TI - MIPs are ancestral ligands for the sex peptide receptor. AB - Upon mating, females of many animal species undergo dramatic changes in their behavior. In Drosophila melanogaster, postmating behaviors are triggered by sex peptide (SP), which is produced in the male seminal fluid and transferred to female during copulation. SP modulates female behaviors via sex peptide receptor (SPR) located in a small subset of internal sensory neurons that innervate the female uterus and project to the CNS. Although required for postmating responses only in these female sensory neurons, SPR is expressed broadly in the CNS of both sexes. Moreover, SPR is also encoded in the genomes of insects that lack obvious SP orthologs. These observations suggest that SPR may have additional ligands and functions. Here, we identify myoinhibitory peptides (MIPs) as a second family of SPR ligands that is conserved across a wide range of invertebrate species. MIPs are potent agonists for Drosophila, Aedes, and Aplysia SPRs in vitro, yet are unable to trigger postmating responses in vivo. In contrast to SP, MIPs are not produced in male reproductive organs, and are not required for postmating behaviors in Drosophila females. We conclude that MIPs are evolutionarily conserved ligands for SPR, which are likely to mediate functions other than the regulation of female reproductive behaviors. PMID- 20308538 TI - Targeting a kinetochore-associated motor protein to kill cancer cells. PMID- 20308539 TI - A genome-scale protein interaction profile of Drosophila p53 uncovers additional nodes of the human p53 network. AB - The genome of the fruitfly Drosophila melanogaster contains a single p53-like protein, phylogenetically related to the ancestor of the mammalian p53 family of tumor suppressors. We reasoned that a comprehensive map of the protein interaction profile of Drosophila p53 (Dmp53) might help identify conserved interactions of the entire p53 family in man. Using a genome-scale in vitro expression cloning approach, we identified 91 previously unreported Dmp53 interactors, considerably expanding the current Drosophila p53 interactome. Looking for evolutionary conservation of these interactions, we tested 41 mammalian orthologs and found that 37 bound to one or more p53-family members when overexpressed in human cells. An RNAi-based functional assay for modulation of the p53 pathway returned five positive hits, validating the biological relevance of these interactions. One p53 interactor is GTPBP4, a nucleolar protein involved in 60S ribosome biogenesis. We demonstrate that GTPBP4 knockdown induces p53 accumulation and activation in the absence of nucleolar disruption. In breast tumors with wild-type p53, increased expression of GTPBP4 correlates with reduced patient survival, emphasizing a potential relevance of this regulatory axis in cancer. PMID- 20308540 TI - Transcriptome and metabolome profiling of field-grown transgenic barley lack induced differences but show cultivar-specific variances. AB - The aim of the present study was to assess possible adverse effects of transgene expression in leaves of field-grown barley relative to the influence of genetic background and the effect of plant interaction with arbuscular mycorrhizal fungi. We conducted transcript profiling, metabolome profiling, and metabolic fingerprinting of wild-type accessions and barley transgenics with seed-specific expression of (1,3-1, 4)-beta-glucanase (GluB) in Baronesse (B) as well as of transgenics in Golden Promise (GP) background with ubiquitous expression of codon optimized Trichoderma harzianum endochitinase (ChGP). We found more than 1,600 differential transcripts between varieties GP and B, with defense genes being strongly overrepresented in B, indicating a divergent response to subclinical pathogen challenge in the field. In contrast, no statistically significant differences between ChGP and GP could be detected based on transcriptome or metabolome analysis, although 22 genes and 4 metabolites were differentially abundant when comparing GluB and B, leading to the distinction of these two genotypes in principle component analysis. The coregulation of most of these genes in GluB and GP, as well as simple sequence repeat-marker analysis, suggests that the distinctive alleles in GluB are inherited from GP. Thus, the effect of the two investigated transgenes on the global transcript profile is substantially lower than the effect of a minor number of alleles that differ as a consequence of crop breeding. Exposing roots to the spores of the mycorrhizal Glomus sp. had little effect on the leaf transcriptome, but central leaf metabolism was consistently altered in all genotypes. PMID- 20308541 TI - Biosynthesis and functions of bacillithiol, a major low-molecular-weight thiol in Bacilli. AB - Bacillithiol (BSH), the alpha-anomeric glycoside of L-cysteinyl-D-glucosamine with L-malic acid, is a major low-molecular-weight thiol in Bacillus subtilis and related bacteria. Here, we identify genes required for BSH biosynthesis and provide evidence that the synthetic pathway has similarities to that established for the related thiol (mycothiol) in the Actinobacteria. Consistent with a key role for BSH in detoxification of electrophiles, the BshA glycosyltransferase and BshB1 deacetylase are encoded in an operon with methylglyoxal synthase. BshB1 is partially redundant in function with BshB2, a deacetylase of the LmbE family. Phylogenomic profiling identified a conserved unknown function protein (COG4365) as a candidate cysteine-adding enzyme (BshC) that co-occurs in genomes also encoding BshA, BshB1, and BshB2. Additional evolutionarily linked proteins include a thioredoxin reductase homolog and two thiol:disulfide oxidoreductases of the DUF1094 (CxC motif) family. Mutants lacking BshA, BshC, or both BshB1 and BshB2 are devoid of BSH. BSH is at least partially redundant in function with other low-molecular-weight thiols: redox proteomics indicates that protein thiols are largely reduced even in the absence of BSH. At the transcriptional level, the induction of genes controlled by two thiol-based regulators (OhrR, Spx) occurs normally. However, BSH null cells are significantly altered in acid and salt resistance, sporulation, and resistance to electrophiles and thiol reactive compounds. Moreover, cells lacking BSH are highly sensitive to fosfomycin, an epoxide-containing antibiotic detoxified by FosB, a prototype for bacillithiol-S transferase enzymes. PMID- 20308542 TI - Annexin A1 regulates TGF-beta signaling and promotes metastasis formation of basal-like breast cancer cells. AB - Annexin A1 (AnxA1) is a candidate regulator of the epithelial- to mesenchymal (EMT)-like phenotypic switch, a pivotal event in breast cancer progression. We show here that AnxA1 expression is associated with a highly invasive basal-like breast cancer subtype both in a panel of human breast cancer cell lines as in breast cancer patients and that AnxA1 is functionally related to breast cancer progression. AnxA1 knockdown in invasive basal-like breast cancer cells reduced the number of spontaneous lung metastasis, whereas additional expression of AnxA1 enhanced metastatic spread. AnxA1 promotes metastasis formation by enhancing TGFbeta/Smad signaling and actin reorganization, which facilitates an EMT-like switch, thereby allowing efficient cell migration and invasion of metastatic breast cancer cells. PMID- 20308543 TI - xCT deficiency accelerates chemically induced tumorigenesis. AB - During the course of inflammation and its resolution, macrophages are exposed to various cytotoxic materials, including reactive oxygen species. Thus, macrophages require a protective machinery against oxidative stress to survive at the inflammatory site. Here, we showed that xCT, a component of transport system x(c)(-), was significantly up-regulated in activated infiltrating cells, including macrophages and neutrophils at the inflammatory site. System x(c)(-) mediates the uptake of extracellular L-cystine and is consequently responsible for maintenance of intracellular glutathione levels. We established a loss-of function mouse mutant line of xCT by N-ethyl-N-nitrosourea mutagenesis. Macrophages from xCT(mu/mu) mice showed cell death in association with the excessive release of high mobility group box chromosomal protein 1 upon stimulation with LPS, suggesting that xCT deficiency causes unremitting inflammation because of the impaired survival of activated macrophages at the inflammatory site. Subcutaneous injection of 3-methylcholanthrene (3-MCA) induced the generation of fibrosarcoma in association with inflammation. When 3-MCA was injected s.c. into mice, xCT mRNA was up-regulated in situ. In xCT(mu/mu) mice, inflammatory cytokines (such as IL-1beta and TNFalpha) were overexpressed, and the generation of 3-MCA-induced fibrosarcoma was accelerated. These results clearly indicate that the defect of the protective system against oxidative stress impaired survival of activated macrophages and subsequently enhanced tumorigenecity. PMID- 20308544 TI - Targeting the protein prenyltransferases efficiently reduces tumor development in mice with K-RAS-induced lung cancer. AB - RAS and RHO proteins, which contribute to tumorigenesis and metastasis, undergo posttranslational modification with an isoprenyl lipid by protein farnesyltransferase (FTase) or protein geranylgeranyltransferase-I (GGTase-I). Inhibitors of FTase and GGTase-I were developed to block RAS-induced malignancies, but their utility has been difficult to evaluate because of off target effects, drug resistance, and toxicity. Moreover, the impact of FTase deficiency and combined FTase/GGTase-I deficiency has not been evaluated with genetic approaches. We found that inactivation of FTase eliminated farnesylation of HDJ2 and H-RAS, prevented H-RAS targeting to the plasma membrane, and blocked proliferation of primary and K-RAS(G12D)-expressing fibroblasts. FTase inactivation in mice with K-RAS-induced lung cancer reduced tumor growth and improved survival, similar to results obtained previously with inactivation of GGTase-I. Simultaneous inactivation of FTase and GGTase-I markedly reduced lung tumors and improved survival without apparent pulmonary toxicity. These data shed light on the biochemical and therapeutic importance of FTase and suggest that simultaneous inhibition of FTase and GGTase-I could be useful in cancer therapeutics. PMID- 20308545 TI - Aberrant temporal and spatial brain activity during rest in patients with chronic pain. AB - In the absence of external stimuli, human hemodynamic brain activity displays slow intrinsic variations. To find out whether such fluctuations would be altered by persistent pain, we asked 10 patients with unrelenting chronic pain of different etiologies and 10 sex- and age-matched control subjects to rest with eyes open during 3-T functional MRI. Independent component analysis was used to identify functionally coupled brain networks. Time courses of an independent component comprising the insular cortices of both hemispheres showed stronger spectral power at 0.12 to 0.25 Hz in patients than in control subjects, with the largest difference at 0.16 Hz. A similar but weaker effect was seen in the anterior cingulate cortex, whereas activity of the precuneus and early visual cortex, used as a control site, did not differ between the groups. In the patient group, seed point-based correlation analysis revealed altered spatial connectivity between insulae and anterior cingulate cortex. The results imply both temporally and spatially aberrant activity of the affective pain-processing areas in patients suffering from chronic pain. The accentuated 0.12- to 0.25-Hz fluctuations in the patient group might be related to altered activity of the autonomic nervous system. PMID- 20308546 TI - Origin and formation of the first two distinct cell types of the inner cell mass in the mouse embryo. AB - A crucial question in mammalian development is how cells of the early embryo differentiate into distinct cell types. The first decision is taken when cells undertake waves of asymmetric division that generate one daughter on the inside and one on the outside of the embryo. After this division, some cells on the inside remain pluripotent and give rise to the epiblast, and hence the future body, whereas others develop into the primitive endoderm, an extraembryonic tissue. How the fate of these inside cells is decided is unknown: Is the process random, or is it related to their developmental origins? To address this question, we traced all cells by live-cell imaging in intact, unmanipulated embryos until the epiblast and primitive endoderm became distinct. This analysis revealed that inner cell mass (ICM) cells have unrestricted developmental potential. However, cells internalized by the first wave of asymmetric divisions are biased toward forming pluripotent epiblast, whereas cells internalized in the next two waves of divisions are strongly biased toward forming primitive endoderm. Moreover, we show that cells internalized by the second wave up regulate expression of Gata6 and Sox17, and changing the expression of these genes determines whether the cells become primitive endoderm. Finally, with our ability to determine the origin of cells, we find that inside cells that are mispositioned when they are born can sort into the correct layer. In conclusion, we propose a model in which the timing of cell internalization, cell position, and cell sorting combine to determine distinct lineages of the preimplantation mouse embryo. PMID- 20308547 TI - Patterns of aging in the long-lived wandering albatross. AB - How does an animal age in natural conditions? Given the multifaceted nature of senescence, identifying the effects of age on physiology and behavior remains challenging. We investigated the effects of age on a broad array of phenotypic traits in a wild, long-lived animal, the wandering albatross. We studied foraging behavior using satellite tracking and activity loggers in males and females (age 6-48+ years), and monitored reproductive performance and nine markers of baseline physiology known to reflect senescence in vertebrates (humoral immunity, oxidative stress, antioxidant defenses, and hormone levels). Age strongly affected foraging behavior and reproductive performance, but not baseline physiology. Consistent with results of mammal and human studies, age affected males and females differently. Overall, our findings demonstrate that age, sex, and foraging ability interact in shaping aging patterns in natural conditions. Specifically, we found an unexpected pattern of spatial segregation by age; old males foraged in remote Antarctica waters, whereas young and middle-aged males never foraged south of the Polar Front. Old males traveled a greater distance but were less active at the sea surface, and returned from sea with elevated levels of stress hormone (corticosterone), mirroring a low foraging efficiency. In contrast to findings in captive animals and short-lived birds, and consistent with disposable soma theory, we found no detectable age-related deterioration of baseline physiology in albatrosses. We propose that foraging efficiency (i.e., the ability of individuals to extract energy from their environment) might play a central role in shaping aging patterns in natural conditions. PMID- 20308548 TI - Xenopus Bsx links daily cell cycle rhythms and pineal photoreceptor fate. AB - In the developing central nervous system, the cell cycle clock plays a crucial role in determining cell fate specification. A second clock, the circadian oscillator, generates daily rhythms of cell cycle progression. Although these two clocks interact, the mechanisms linking circadian cell cycle progression and cell fate determination are still poorly understood. A convenient system to address this issue is the pineal organ of lower vertebrates, which contains only two neuronal types, photoreceptors and projection neurons. In particular, photoreceptors constitute the core of the pineal circadian system, being able to transduce daily light inputs into the rhythmical production of melatonin. However, the genetic program leading to photoreceptor fate largely remains to be deciphered. Here, we report a previously undescribed function for the homeobox gene Bsx in controlling pineal proliferation and photoreceptor fate in Xenopus. We show that Xenopus Bsx (Xbsx) is expressed rhythmically in postmitotic photoreceptor precursors, reaching a peak during the night, with a cycle that is complementary to the daily rhythms of S-phase entry displayed by pineal cells. Xbsx knockdown results in increased night levels of pineal proliferation, whereas activation of a GR-Xbsx protein flattens the daily rhythms of S-phase entry to the lowest level. Furthermore, evidence is presented that Xbsx is necessary and sufficient to promote a photoreceptor fate. Altogether, these data indicate that Xbsx plays a dual role in contributing to shape the profile of the circadian cell cycle progression and in the specification of pineal photoreceptors, thus acting as a unique link between these two events. PMID- 20308550 TI - The phosphatase and tensin homolog regulates epidermal growth factor receptor (EGFR) inhibitor response by targeting EGFR for degradation. AB - The phosphatase and tensin homolog (PTEN) is a tumor suppressor that is inactivated in many human cancers. PTEN loss has been associated with resistance to inhibitors of the epidermal growth factor receptor (EGFR), but the molecular basis of this resistance is unclear. It is believed that unopposed phosphatidylinositol-3-kinase (PI3K) activation through multiple receptor tyrosine kinases (RTKs) can relieve PTEN-deficient cancers from their "dependence" on EGFR or any other single RTK for survival. Here we report a distinct resistance mechanism whereby PTEN inactivation specifically raises EGFR activity by impairing the ligand-induced ubiquitylation and degradation of the activated receptor through destabilization of newly formed ubiquitin ligase Cbl complexes. PTEN-associated resistance to EGFR kinase inhibitors is phenocopied by expression of dominant negative Cbl and can be overcome by more complete EGFR kinase inhibition. PTEN inactivation does not confer resistance to inhibitors of the MET or PDGFRA kinase. Our study identifies a critical role for PTEN in EGFR signal termination and suggests that more potent EGFR inhibition should overcome resistance caused by PI3K pathway activation. PMID- 20308549 TI - Multiple aquatic invasions by an endemic, terrestrial Hawaiian moth radiation. AB - Insects are the most diverse form of life on the planet, dominating both terrestrial and freshwater ecosystems, yet no species has a life stage able to breath, feed, and develop either continually submerged or without access to water. Such truly amphibious insects are unrecorded. In mountain streams across the Hawaiian Islands, some caterpillars in the endemic moth genus Hyposmocoma are truly amphibious. These larvae can breathe and feed indefinitely both above and below the water's surface and can mature completely submerged or dry. Remarkably, a molecular phylogeny based on 2,243 bp from both nuclear (elongation factor 1alpha and carbomoylphosphate synthase) and mitochondrial (cytochrome oxidase I) genes representing 216 individuals and 89 species of Hyposmocoma reveals that this amphibious lifestyle is an example of parallel evolution and has arisen from strictly terrestrial clades at least three separate times in the genus starting more than 6 million years ago, before the current high islands existed. No other terrestrial genus of animals has sponsored so many independent aquatic invasions, and no other insects are able to remain active indefinitely above and below water. Why and how Hyposmocoma, an overwhelmingly terrestrial group, repeatedly evolved unprecedented aquatic species is unclear, although there are many other evolutionary anomalies across the Hawaiian archipelago. The uniqueness of the community assemblages of Hawaii's isolated biota is likely critical in generating such evolutionary novelty because this amphibious ecology is unknown anywhere else. PMID- 20308551 TI - Progressive renal injury from transgenic expression of human carbonic anhydrase IV folding mutants is enhanced by deficiency of p58IPK. AB - Mutations in the human carbonic anhydrase IV (hCAIV) have been associated with retinal degeneration in an autosomal-dominant form of retinitis pigmentosa (RP17). Prior in vitro cell culture studies confirmed that all of the RP17 associated hCAIV mutations cause protein misfolding, leading to endoplasmic reticulum (ER) stress-induced apoptosis in cells expressing the mutant proteins. To evaluate the physiological impacts of these folding mutants in other carbonic anhydrase IV-producing tissues, we generated two transgenic mouse lines expressing R219S or R14W hCAIV under control of the endogenous hCAIV promoter. Expression of either of these mutant proteins in kidneys caused progressive renal injury in male transgenic mice as evidenced by an age-dependent increase in the tubule cell apoptosis starting at approximately 20 weeks of age and vacuolization throughout the renal cortex in older mice. Up-regulation of the ER chaperone, BiP, was observed in the cells of the renal cortex of the male transgenic mice, suggesting ER stress as a causal factor for the renal injury. The renal injury inflicted by expression of the folding mutants was markedly enhanced by haploinsufficiency of the ER cochaperone p58(IPK). The transgenic mice expressing the hCAIV folding mutants on a p58(IPK) heterozygous background showed extensive renal tubular apoptosis by approximately 10 weeks of age in both male and female mice. These data indicate that expression of the RP17-associated folding mutants of hCAIV can adversely affect tissues beyond the retina and their in vivo proteotoxicity is sensitive to modulation of the protein folding environment of the ER. PMID- 20308552 TI - Truncated beta-amyloid peptide channels provide an alternative mechanism for Alzheimer's Disease and Down syndrome. AB - Full-length amyloid beta peptides (Abeta(1-40/42)) form neuritic amyloid plaques in Alzheimer's disease (AD) patients and are implicated in AD pathology. However, recent transgenic animal models cast doubt on their direct role in AD pathology. Nonamyloidogenic truncated amyloid-beta fragments (Abeta(11-42) and Abeta(17-42)) are also found in amyloid plaques of AD and in the preamyloid lesions of Down syndrome, a model system for early-onset AD study. Very little is known about the structure and activity of these smaller peptides, although they could be the primary AD and Down syndrome pathological agents. Using complementary techniques of molecular dynamics simulations, atomic force microscopy, channel conductance measurements, calcium imaging, neuritic degeneration, and cell death assays, we show that nonamyloidogenic Abeta(9-42) and Abeta(17-42) peptides form ion channels with loosely attached subunits and elicit single-channel conductances. The subunits appear mobile, suggesting insertion of small oligomers, followed by dynamic channel assembly and dissociation. These channels allow calcium uptake in amyloid precursor protein-deficient cells. The channel mediated calcium uptake induces neurite degeneration in human cortical neurons. Channel conductance, calcium uptake, and neurite degeneration are selectively inhibited by zinc, a blocker of amyloid ion channel activity. Thus, truncated Abeta fragments could account for undefined roles played by full length Abetas and provide a unique mechanism of AD and Down syndrome pathologies. The toxicity of nonamyloidogenic peptides via an ion channel mechanism necessitates a reevaluation of the current therapeutic approaches targeting the nonamyloidogenic pathway as avenue for AD treatment. PMID- 20308553 TI - Cultural differences are not always reducible to individual differences. AB - We show that differences in social orientation and in cognition that exist between cultures and social classes do not necessarily have counterparts in individual differences within those groups. Evidence comes from a large-scale study conducted with 10 measures of independent vs. interdependent social orientation and 10 measures of analytic vs. holistic cognitive style. The social measures successfully distinguish between interdependence (viewing oneself as embedded in relations with others) and independence (viewing oneself as disconnected from others) at the group level. However, the correlations among the measures were negligible. Similar results were obtained for the cognitive measures, for which there are no coherent individual differences despite the validity of the construct at the group level. We conclude that behavioral constructs that distinguish among groups need not be valid as measures of individual differences. PMID- 20308554 TI - A sense of direction in human entorhinal cortex. AB - Finding our way in spatial environments is an essential part of daily life. How do we come to possess this sense of direction? Extensive research points to the hippocampus and entorhinal cortex (EC) as key neural structures underlying spatial navigation. To better understand this system, we examined recordings of single-neuron activity from neurosurgical patients playing a virtual-navigation video game. In addition to place cells, which encode the current virtual location, we describe a unique cell type, EC path cells, the activity of which indicates whether the patient is taking a clockwise or counterclockwise path around the virtual square road. We find that many EC path cells exhibit this directional activity throughout the environment, in contrast to hippocampal neurons, which primarily encode information about specific locations. More broadly, these findings support the hypothesis that EC encodes general properties of the current context (e.g., location or direction) that are used by hippocampus to build unique representations reflecting combinations of these properties. PMID- 20308555 TI - Coherent and incoherent inference in phylogeography and human evolution. AB - A hypothesis is nested within a more general hypothesis when it is a special case of the more general hypothesis. Composite hypotheses consist of more than one component, and in many cases different composite hypotheses can share some but not all of these components and hence are overlapping. In statistics, coherent measures of fit of nested and overlapping composite hypotheses are technically those measures that are consistent with the constraints of formal logic. For example, the probability of the nested special case must be less than or equal to the probability of the general model within which the special case is nested. Any statistic that assigns greater probability to the special case is said to be incoherent. An example of incoherence is shown in human evolution, for which the approximate Bayesian computation (ABC) method assigned a probability to a model of human evolution that was a thousand-fold larger than a more general model within which the first model was fully nested. Possible causes of this incoherence are identified, and corrections and restrictions are suggested to make ABC and similar methods coherent. Another coalescent-based method, nested clade phylogeographic analysis, is coherent and also allows the testing of individual components of composite hypotheses, another attribute lacking in ABC and other coalescent-simulation approaches. Incoherence is a highly undesirable property because it means that the inference is mathematically incorrect and formally illogical, and the published incoherent inferences on human evolution that favor the out-of-Africa replacement hypothesis have no statistical or logical validity. PMID- 20308556 TI - Toll-like receptor 8-mediated activation of murine plasmacytoid dendritic cells by vaccinia viral DNA. AB - Plasmacytoid dendritic cells (pDCs) play a critical role in antiviral immunity through their ability to produce large amounts of type I IFNs. Activation of pDCs upon viral infection has been shown to be dependent on MyD88 and mediated by Toll like receptors (TLR) 7 and 9, which sense viral ssRNA and CpG DNA, respectively. In this study, we showed that murine pDC recognition of vaccinia virus (VV), a dsDNA virus, was MyD88-dependent but TLR9-independent. Using HEK293 cells transfected with murine TLR7 or TLR8 and a NF-kappaB luciferase reporter, we demonstrated that stimulation of TLR8-, but not TLR7-, transfected cells with either VV or VV DNA resulted in substantial NF-kappaB activation, and that siRNA mediated knockdown of TLR8 expression in pDCs led to a complete ablation of VV induced type I IFN production. We further identified that the VV genome was rich in poly(A)/T sequences, and synthetic poly(A) and poly T oligodeoxynucleotides were capable of activating pDCs in a TLR8-dependent manner. In vivo, TLR8-MyD88 dependent pDC activation played a critical role in innate immune control of VV infection. Collectively, our data are unique in demonstrating that TLR8 is required for sensing poly(A)/T-rich DNA in pDCs, and that murine TLR8 is functional in the context of a viral infection. PMID- 20308557 TI - UV radiation suppresses experimental autoimmune encephalomyelitis independent of vitamin D production. AB - Although the exact cause of multiple sclerosis (MS) is unknown, a number of genetic and environmental factors are thought to influence MS susceptibility. One potential environmental factor is sunlight and the subsequent production of vitamin D. A number of studies have correlated decreased exposure to UV radiation (UVR) and low serum 25-hydroxyvitamin D(3) [25(OH)D(3)] levels with an increased risk for developing MS. Furthermore, both UVR and the active form of vitamin D, 1alpha,25-dihydroxyvitamin D(3), suppress disease in the experimental autoimmune encephalomyelitis (EAE) animal model of MS. These observations led to the hypothesis that UVR likely suppresses disease through the increased production of vitamin D. However, UVR can suppress the immune system independent of vitamin D. Therefore, it is unclear whether UVR, vitamin D, or both are necessary for the putative decrease in MS susceptibility. We have probed the ability of UVR to suppress disease in the EAE model of MS and assessed the effect of UVR on serum 25(OH)D(3) and calcium levels. Our results indicate that continuous treatment with UVR dramatically suppresses clinical signs of EAE. Interestingly, disease suppression occurs with only a modest, transient increase in serum 25(OH)D(3) levels. Further analysis demonstrated that the levels of 25(OH)D(3) obtained upon UVR treatment were insufficient to suppress EAE independent of UVR treatment. These results suggest that UVR is likely suppressing disease independent of vitamin D production, and that vitamin D supplementation alone may not replace the ability of sunlight to reduce MS susceptibility. PMID- 20308558 TI - Coordination of Rab8 and Rab11 in primary ciliogenesis. AB - Primary cilia are microtubule-based membrane projections located at the surface of many cells. Defects in primary cilia formation have been implicated in a number of genetic disorders, such as Bardet-Biedl Syndrome and Polycystic Kidney Disease. Recent studies have demonstrated that polarized vesicular transport involving Rab8 and its guanine nucleotide-exchange factor Rabin8 is essential for primary ciliogenesis. Here we report that Rabin8 is a direct downstream effector of Rab11, which functions in membrane trafficking from the trans-Golgi network and recycling endosomes. Rab11, in its GTP-bound form, interacts with Rabin8 and kinetically stimulates the guanine nucleotide-exchange activity of Rabin8 toward Rab8. Rab11 is enriched at the base of the primary cilia and inhibition of Rab11 function by a dominant-negative mutant or RNA interference blocks primary ciliogenesis. Our results suggest that Rab GTPases coordinate with each other in the regulation of vesicular trafficking during primary ciliogenesis. PMID- 20308559 TI - P53-induced microRNA-107 inhibits HIF-1 and tumor angiogenesis. AB - The pathway involving the tumor suppressor gene TP53 can regulate tumor angiogenesis by unclear mechanisms. Here we show that p53 regulates hypoxic signaling through the transcriptional regulation of microRNA-107 (miR-107). We found that miR-107 is a microRNA expressed by human colon cancer specimens and regulated by p53. miR-107 decreases hypoxia signaling by suppressing expression of hypoxia inducible factor-1beta (HIF-1beta). Knockdown of endogenous miR-107 enhances HIF-1beta expression and hypoxic signaling in human colon cancer cells. Conversely, overexpression of miR-107 inhibits HIF-1beta expression and hypoxic signaling. Furthermore, overexpression of miR-107 in tumor cells suppresses tumor angiogenesis, tumor growth, and tumor VEGF expression in mice. Finally, in human colon cancer specimens, expression of miR-107 is inversely associated with expression of HIF-1beta. Taken together these data suggest that miR-107 can mediate p53 regulation of hypoxic signaling and tumor angiogenesis. PMID- 20308560 TI - In colorectal cancer mast cells contribute to systemic regulatory T-cell dysfunction. AB - T-regulatory cells (Treg) and mast cells (MC) are abundant in colorectal cancer (CRC) tumors. Interaction between the two is known to promote immune suppression or loss of Treg functions and autoimmunity. Here, we demonstrate that in both human CRC and murine polyposis the outcome of this interaction is the generation of potently immune suppressive but proinflammatory Treg (DeltaTreg). These Treg shut down IL10, gain potential to express IL17, and switch from suppressing to promoting MC expansion and degranulation. This change is also brought about by direct coculture of MC and Treg, or culture of Treg in medium containing IL6 and IL2. IL6 deficiency in the bone marrow of mice susceptible to polyposis eliminated IL17 production by the polyp infiltrating Treg, but did not significantly affect the growth of polyps or the generation of proinflammatory Treg. IL6-deficient MC could generate proinflammatory Treg. Thus, MC induce Treg to switch function and escalate inflammation in CRC without losing T-cell suppressive properties. IL6 and IL17 are not needed in this process. PMID- 20308561 TI - Estrogen receptor ESR1 controls cell migration by repressing chemokine receptor CXCR4 in the zebrafish posterior lateral line system. AB - The primordium that generates the embryonic posterior lateral line of zebrafish migrates from the head to the tip of the tail along a trail of SDF1-producing cells. This migration critically depends on the presence of the SDF1 receptor CXCR4 in the leading region of the primordium and on the presence of a second SDF1 receptor, CXCR7, in the trailing region of the primordium. Here we show that inactivation of the estrogen receptor ESR1 results in ectopic expression of cxcr4b throughout the primordium, whereas ESR1 overexpression results in a reciprocal reduction in the domain of cxcr4b expression, suggesting that ESR1 acts as a repressor of cxcr4b. This finding could explain why estrogens significantly decrease the metastatic ability of ESR-positive breast cancer cells. ESR1 inactivation also leads to extinction of cxcr7b expression in the trailing cells of the migrating primordium; this effect is indirect, however, and due to the down-regulation of cxcr7b by ectopic SDF1/CXCR4 signaling in the trailing region. Both ESR1 inactivation and overexpression result in aborted migration, confirming the importance of this receptor in the control of SDF1 dependent migration. PMID- 20308562 TI - Hypoxia inducible microRNA 210 attenuates keratinocyte proliferation and impairs closure in a murine model of ischemic wounds. AB - Ischemia complicates wound closure. Here, we are unique in presenting a murine ischemic wound model that is based on bipedicle flap approach. Using this model of ischemic wounds we have sought to elucidate how microRNAs may be implicated in limiting wound re-epithelialization under hypoxia, a major component of ischemia. Ischemia, evaluated by laser Doppler as well as hyperspectral imaging, limited blood flow and lowered tissue oxygen saturation. EPR oximetry demonstrated that the ischemic wound tissue had pO(2) <10 mm Hg. Ischemic wounds suffered from compromised macrophage recruitment and delayed wound epithelialization. Specifically, epithelial proliferation, as determined by Ki67 staining, was compromised. In vivo imaging showed massive hypoxia inducible factor-1alpha (HIF 1alpha) stabilization in ischemic wounds, where HIF-1alpha induced miR-210 expression that, in turn, silenced its target E2F3, which was markedly down regulated in the wound-edge tissue of ischemic wounds. E2F3 was recognized as a key facilitator of cell proliferation. In keratinocytes, knock-down of E2F3 limited cell proliferation. Forced stabilization of HIF-1alpha using Ad-VP16- HIF 1alpha under normoxic conditions up-regulated miR-210 expression, down-regulated E2F3, and limited cell proliferation. Studies using cellular delivery of miR-210 antagomir and mimic demonstrated a key role of miR-210 in limiting keratinocyte proliferation. In summary, these results are unique in presenting evidence demonstrating that the hypoxia component of ischemia may limit wound re epithelialization by stabilizing HIF-1alpha, which induces miR-210 expression, resulting in the down-regulation of the cell-cycle regulatory protein E2F3. PMID- 20308563 TI - Genetic variation of melatonin productivity in laboratory mice under domestication. AB - Melatonin is a pineal hormone produced at night; however, many strains of laboratory mice are deficient in melatonin. Strangely enough, the gene encoding HIOMT enzyme (also known as ASMT) that catalyzes the last step of melatonin synthesis is still unidentified in the house mouse (Mus musculus) despite the completion of the genome sequence. Here we report the identification of the mouse Hiomt gene, which was mapped to the pseudoautosomal region (PAR) of sex chromosomes. The gene was highly polymorphic, and nonsynonymous SNPs were found in melatonin-deficient strains. In C57BL/6 strain, there are two mutations, both of which markedly reduce protein expression. Mutability of the Hiomt likely due to a high recombination rate in the PAR could be the genomic basis for the high prevalence of melatonin deficiency. To understand the physiologic basis, we examined a wild-derived strain, MSM/Ms, which produced melatonin more under a short-day condition than a long-day condition, accompanied by increased Hiomt expression. We generated F2 intercrosses between MSM/Ms and C57BL/6 strains and N2 backcrosses to investigate the role of melatonin productivity on the physiology of mice. Although there was no apparent effect of melatonin productivity on the circadian behaviors, testis development was significantly promoted in melatonin-deficient mice. Exogenous melatonin also had the antigonadal action in mice of a melatonin-deficient strain. These findings suggest a favorable impact of melatonin deficiency due to Hiomt mutations on domestic mice in breeding colonies. PMID- 20308564 TI - HR23B is a biomarker for tumor sensitivity to HDAC inhibitor-based therapy. AB - Histone deacetylase (HDAC) inhibitors are emergent cancer drugs. HR23B is a candidate cancer biomarker identified in a genome-wide loss-of-function screen which influences sensitivity to HDAC inhibitors. Because HDAC inhibitors have found clinical utility in cutaneous T-cell lymphoma (CTCL), we evaluated the role of HR23B in CTCL cells. Our results show that HR23B governs the sensitivity of CTCL cells to HDAC inhibitors. Furthermore, proteasome activity is deregulated in HDAC inhibitor-treated CTCL cells through a mechanism dependent upon HR23B, and HDAC inhibitors sensitize CTCL cells to the effects of proteasome inhibitors. The predictive power of HR23B for clinical response to HDAC inhibitors was investigated through an analysis of a unique collection of CTCL biopsies taken from a phase II clinical trial, where there was a frequent coincidence between HR23B expression and clinical response to HDAC inhibitor. Our study supports the personalized medicine approach for treating cancer and the increasing drive to translate laboratory-based findings into clinical utility. PMID- 20308565 TI - ATP-gated P2X3 receptors constitute a positive autocrine signal for insulin release in the human pancreatic beta cell. AB - Extracellular ATP has been proposed as a paracrine signal in rodent islets, but it is unclear what role ATP plays in human islets. We now show the presence of an ATP signaling pathway that enhances the human beta cell's sensitivity and responsiveness to glucose fluctuations. By using in situ hybridization, RT-PCR, immunohistochemistry, and Western blotting as well as recordings of cytoplasmic free Ca(2+) concentration, [Ca(2+)](i), and hormone release in vitro, we show that human beta cells express ionotropic ATP receptors of the P2X(3) type and that activation of these receptors by ATP coreleased with insulin amplifies glucose-induced insulin secretion. Released ATP activates P2X(3) receptors in the beta-cell plasma membrane, resulting in increased [Ca(2+)](i) and enhanced insulin secretion. Therefore, in human islets, released ATP forms a positive autocrine feedback loop that sensitizes the beta cell's secretory machinery. This may explain how the human pancreatic beta cell can respond so effectively to relatively modest changes in glucose concentration under physiological conditions in vivo. PMID- 20308566 TI - Imaging extrasynaptic glutamate dynamics in the brain. AB - Glutamate is the major neurotransmitter in the brain, mediating point-to-point transmission across the synaptic cleft in excitatory synapses. Using a glutamate imaging method with fluorescent indicators, we show that synaptic activity generates extrasynaptic glutamate dynamics in the vicinity of active synapses. These glutamate dynamics had magnitudes and durations sufficient to activate extrasynaptic glutamate receptors in brain slices. We also observed crosstalk between synapses--i.e., summation of glutamate released from neighboring synapses. Furthermore, we successfully observed that sensory input from the extremities induced extrasynaptic glutamate dynamics within the appropriate sensory area of the cerebral cortex in vivo. Thus, the present study clarifies the spatiotemporal features of extrasynaptic glutamate dynamics, and opens up an avenue to directly visualizing synaptic activity in live animals. PMID- 20308567 TI - Dynamic evolution of translation initiation mechanisms in prokaryotes. AB - It is generally believed that prokaryotic translation is initiated by the interaction between the Shine-Dalgarno (SD) sequence in the 5' UTR of an mRNA and the anti-SD sequence in the 3' end of a 16S ribosomal RNA. However, there are two exceptional mechanisms, which do not require the SD sequence for translation initiation: one is mediated by a ribosomal protein S1 (RPS1) and the other used leaderless mRNA that lacks its 5' UTR. To understand the evolutionary changes of the mechanisms of translation initiation, we examined how universal the SD sequence is as an effective initiator for translation among prokaryotes. We identified the SD sequence from 277 species (249 eubacteria and 28 archaebacteria). We also devised an SD index that is a proportion of SD containing genes in which the differences of GC contents are taken into account. We found that the SD indices varied among prokaryotic species, but were similar within each phylum. Although the anti-SD sequence is conserved among species, loss of the SD sequence seems to have occurred multiple times, independently, in different phyla. For those phyla, RPS1-mediated or leaderless mRNA-used mechanisms of translation initiation are considered to be working to a greater extent. Moreover, we also found that some species, such as Cyanobacteria, may acquire new mechanisms of translation initiation. Our findings indicate that, although translation initiation is indispensable for all protein-coding genes in the genome of every species, its mechanisms have dynamically changed during evolution. PMID- 20308568 TI - HLA-A alleles and infectious mononucleosis suggest a critical role for cytotoxic T-cell response in EBV-related Hodgkin lymphoma. AB - A proportion of classical Hodgkin lymphoma (HL) is believed to be causally related to infection with the ubiquitous lymphotropic EBV. The determining factors for development of EBV-related HL remain poorly understood, but likely involve immunological control of the viral infection. Accordingly, markers of the HLA class I region have been associated with risk of EBV-related HL. To study the host genetic component of EBV-related HL further, we investigated the lymphoma's association with HLA-A*01 and HLA-A*02 simultaneously in the setting of infectious mononucleosis (IM), a risk factor for EBV-related HL, in a case-series analysis including 278 EBV-related and 656 EBV-unrelated cases of HL. By logistic regression, HLA-A*01 alleles [odds ratio (OR) per allele, 2.15; 95% CI, 1.60 2.88] were associated with increased and HLA-A*02 alleles (OR per allele, 0.70; 95% CI, 0.51-0.97) with decreased risk of EBV-related HL. These allele-specific associations corresponded to nearly 10-fold variation in risk of EBV-related HL between HLA-A*01 and HLA-A*02 homozygotes. History of IM was also associated with risk of EBV-related HL (OR, 3.40; 95% CI, 1.74-6.66). The association between history of IM and EBV-related HL was not seen in the presence of HLA-A*02 because this allele appeared to neutralize the effect of IM on EBV-related HL risk. Our findings suggest that HLA class I-restricted EBV-specific cytotoxic T-cell responses and events in the early immune response to EBV infection in IM play critical roles in the pathogenesis of EBV-related HL. PMID- 20308569 TI - Zbtb20 is essential for the specification of CA1 field identity in the developing hippocampus. AB - The development of hippocampal circuitry depends on the proper assembly of correctly specified and fully differentiated hippocampal neurons. Little is known about factors that control the hippocampal specification. Here, we show that zinc finger protein Zbtb20 is essential for the specification of hippocampal CA1 field identity. We found that Zbtb20 expression was initially activated in the hippocampal anlage at the onset of corticogenesis, and persisted in immature hippocampal neurons. Targeted deletion of Zbtb20 in mice did not compromise the progenitor proliferation in the hippocampal and adjacent transitional ventricular zone, but led to the transformation of the hippocampal CA1 field into a transitional neocortex-like structure, as evidenced by cytoarchitectural, neuronal migration, and gene expression phenotypes. Correspondingly, the subiculum was ectopically located adjacent to the CA3 in mutant. Although the field identities of the mutant CA3 and dentate gyrus (DG) were largely maintained, their projections were severely impaired. The hippocampus of Zbtb20 null mice was reduced in size, and exhibited increased apoptotic cell death during postnatal development. Our data establish an essential role of Zbtb20 in the specification of CA1 field identity by repressing adjacent transitional neocortex-specific fate determination. PMID- 20308570 TI - Association of RIG-I with innate immunity of ducks to influenza. AB - Ducks and wild waterfowl perpetuate all strains of influenza viruses in nature. In their natural host, influenza viruses typically cause asymptomatic infection and little pathology. Ducks are often resistant to influenza viruses capable of killing chickens. Here, we show that the influenza virus sensor, RIG-I, is present in ducks and plays a role in clearing an influenza infection. We show evidence suggesting that RIG-I may be absent in chickens, providing a plausible explanation for their increased susceptibility to influenza viruses compared with ducks. RIG-I detects RNA ligands derived from uncapped viral transcripts and initiates the IFN response. In this study, we show that the chicken embryonic fibroblast cell line, DF-1, cannot respond to a RIG-I ligand. However, transfection of duck RIG-I into DF-1 cells rescues the detection of ligand and induces IFN-beta promoter activity. Additionally, DF-1 cells expressing duck RIG I have an augmented IFN response resulting in decreased influenza replication after challenge with either low or highly pathogenic avian influenza virus. Implicating RIG-I in the antiviral response to an infection in vivo, we found that RIG-I expression is induced 200 fold, early in an innate immune response in ducks challenged with the H5N1 virus A/Vietnam/1203/04. Finding this natural disease resistance gene in ducks opens the possibility of increasing influenza resistance through creation of a transgenic chicken. PMID- 20308571 TI - Gonadotropin-positive pituitary tumors accompanied by ovarian tumors in aging female ERbeta-/- mice. AB - At 2 years of age, 100% (23/23) of ERbeta(-/-) female mice have developed large pituitary and ovarian tumors. The pituitary tumors are gonadotropin-positive and the ovarian tumors are sex cord (less differentiated) and granulosa cell tumors (differentiated and estrogen secreting). No male mice had pituitary tumors and no pituitary or ovarian tumors developed in ERalpha(-/-) mice or in ERalphabeta(-/-) double knockout mice. The tumors have high proliferation indices, are ERalpha positive, ERbeta-negative, and express high levels of nuclear phospho-SMAD3. Mice with granulosa cell tumors also had hyperproliferative endometria. The cause of the pituitary tumors appeared to be excessive secretion of gonadotropin releasing hormone (GnRH) from the hypothalamus resulting from high expression of NPY. The ovarian phenotype is similar to that seen in mice where inhibin is ablated. The data indicate that ERbeta plays an important role in regulating GnRH secretion. We suggest that in the absence of ERbeta, the proliferative action of FSH/SMAD3 is unopposed and the high proliferation leads to the development of ovarian tumors. The absence of tumors in the ERalphabeta(-/-) mice suggests that tumor development requires the presence of ERalpha. PMID- 20308572 TI - Systematic discovery of nonobvious human disease models through orthologous phenotypes. AB - Biologists have long used model organisms to study human diseases, particularly when the model bears a close resemblance to the disease. We present a method that quantitatively and systematically identifies nonobvious equivalences between mutant phenotypes in different species, based on overlapping sets of orthologous genes from human, mouse, yeast, worm, and plant (212,542 gene-phenotype associations). These orthologous phenotypes, or phenologs, predict unique genes associated with diseases. Our method suggests a yeast model for angiogenesis defects, a worm model for breast cancer, mouse models of autism, and a plant model for the neural crest defects associated with Waardenburg syndrome, among others. Using these models, we show that SOX13 regulates angiogenesis, and that SEC23IP is a likely Waardenburg gene. Phenologs reveal functionally coherent, evolutionarily conserved gene networks-many predating the plant-animal divergence capable of identifying candidate disease genes. PMID- 20308573 TI - Ribosome-associated peroxiredoxins suppress oxidative stress-induced de novo formation of the [PSI+] prion in yeast. AB - Peroxiredoxins (Prxs) are ubiquitous antioxidants that protect cells against oxidative stress. We show that the yeast Tsa1/Tsa2 Prxs colocalize to ribosomes and function to protect the Sup35 translation termination factor against oxidative stress-induced formation of its heritable [PSI(+)] prion conformation. In a tsa1 tsa2 [psi(-)] [PIN(+)] strain, the frequency of [PSI(+)] de novo formation is significantly elevated. The Tsa1/Tsa2 Prxs, like other 2-Cys Prxs, have dual activities as peroxidases and chaperones, and we show that the peroxidase activity is required to suppress spontaneous de novo [PSI(+)] prion formation. Molecular oxygen is required for [PSI(+)] prion formation as growth under anaerobic conditions prevents prion formation in the tsa1 tsa2 mutant. Conversely, oxidative stress conditions induced by exposure to hydrogen peroxide elevates the rate of de novo [PSI(+)] prion formation leading to increased suppression of all three termination codons in the tsa1 tsa2 mutant. Altered translational fidelity in [PSI(+)] strains may provide a mechanism that promotes genetic variation and phenotypic diversity (True HL, Lindquist SL (2000) Nature 407:477-483). In agreement, we find that prion formation provides yeast cells with an adaptive advantage under oxidative stress conditions, as elimination of the [PSI(+)] prion from tsa1 tsa2 mutants renders the resulting [psi(-)] [pin(-)] cells hypersensitive to hydrogen peroxide. These data support a model in which Prxs function to protect the ribosomal machinery against oxidative damage, but when these systems become overwhelmed, [PSI(+)] prion formation provides a mechanism for uncovering genetic traits that aid survival during oxidative stress conditions. PMID- 20308574 TI - Primary state formation in the Viru Valley, north coast of Peru. AB - The origins of urban life and functioning states are two of the most fascinating research problems in anthropological archeology and a topic that has intrigued generations of scholars working on the Peruvian north coast. In this region, Andeanists have documented the rise of Moche as a dominant culture during the first millennium A.D., and the emergence of urban life and stately institutions at this society's principal center. Although there is a broad consensus that Moche represents an archaic state, it is still unclear whether it is an example of primary state formation or a case of a second-generation state. To document this question, archaeological excavations were recently carried out at the Gallinazo Group site in the Viru Valley. Results from a radiocarbon dating program indicate that a functioning state probably emerged in this valley during the second century B.C., possibly preceding Moche by a few centuries. These results necessarily raise question regarding the nature of state development on the north coast of Peru and, in particular, whether there was a single center of state development in this region or multiple sites where similar conditions and processes led to the parallel emergence of functioning states. PMID- 20308575 TI - Drosophila topo IIIalpha is required for the maintenance of mitochondrial genome and male germ-line stem cells. AB - Topoisomerase IIIalpha (topo IIIalpha), a member of the conserved Type IA subfamily of topoisomerases, is required for the cell proliferation in mitotic tissues, but has a lesser effect on DNA endoreplication. The top3alpha gene encodes two forms of protein by utilizing alternative translation initiation sites: one (short form) with the nuclear localization signal only, exclusively localized in the nuclei, and the other (long form), retaining a mitochondrial import sequence at the N-terminus and the nuclear localization sequence at the C terminus, localized primarily in the mitochondria, though with a small portion in the nuclei. Both forms of topo IIIalpha can rescue the viability of null mutants of top3alpha. No apparent defect is associated with the flies rescued by the long form; short-form-rescued flies (referred to as M1L), however, exhibit defects in fertilities. M1L females are sterile. They can lay eggs but with mitochondrial DNA (mtDNA) copy number and ATP content decreased by 20- and 2- to 3-fold, respectively, and they fail to hatch. Of the newly eclosed M1L males, 33% are completely sterile, whereas the rest have residual fertilities that are quickly lost in 6 days. The fertility loss of M1L males is caused by the disruption of the individualization complex and a progressive loss of germ-line stem cells. This study implicates topo IIIalpha in the maintenance of mtDNA and male germ line stem cells, and thus is a causative candidate for genetic disorders associated with mtDNA depletion. PMID- 20308576 TI - One-microsecond molecular dynamics simulation of channel gating in a nicotinic receptor homologue. AB - Recently discovered bacterial homologues of eukaryotic pentameric ligand-gated ion channels, such as the Gloeobacter violaceus receptor (GLIC), are increasingly used as structural and functional models of signal transduction in the nervous system. Here we present a one-microsecond-long molecular dynamics simulation of the GLIC channel pH stimulated gating mechanism. The crystal structure of GLIC obtained at acidic pH in an open-channel form is equilibrated in a membrane environment and then instantly set to neutral pH. The simulation shows a channel closure that rapidly takes place at the level of the hydrophobic furrow and a progressively increasing quaternary twist. Two major events are captured during the simulation. They are initiated by local but large fluctuations in the pore, taking place at the top of the M2 helix, followed by a global tertiary relaxation. The two-step transition of the first subunit starts within the first 50 ns of the simulation and is followed at 450 ns by its immediate neighbor in the pentamer, which proceeds with a similar scenario. This observation suggests a possible two-step domino-like tertiary mechanism that takes place between adjacent subunits. In addition, the dynamical properties of GLIC described here offer an interpretation of the paradoxical properties of a permeable A13'F mutant whose crystal structure determined at 3.15 A shows a pore too narrow to conduct ions. PMID- 20308577 TI - Tin-containing zeolites are highly active catalysts for the isomerization of glucose in water. AB - The isomerization of glucose into fructose is a large-scale reaction for the production of high-fructose corn syrup (HFCS; reaction performed by enzyme catalysts) and recently is being considered as an intermediate step in the possible route of biomass to fuels and chemicals. Here, it is shown that a large pore zeolite that contains tin (Sn-Beta) is able to isomerize glucose to fructose in aqueous media with high activity and selectivity. Specifically, a 10% (wt/wt) glucose solution containing a catalytic amount of Sn-Beta (150 Sn:glucose molar ratio) gives product yields of approximately 46% (wt/wt) glucose, 31% (wt/wt) fructose, and 9% (wt/wt) mannose after 30 min and 12 min of reaction at 383 K and 413 K, respectively. This reactivity is achieved also when a 45 wt% glucose solution is used. The properties of the large-pore zeolite greatly influence the reaction behavior because the reaction does not proceed with a medium-pore zeolite, and the isomerization activity is considerably lower when the metal centers are incorporated in ordered mesoporous silica (MCM-41). The Sn-Beta catalyst can be used for multiple cycles, and the reaction stops when the solid is removed, clearly indicating that the catalysis is occurring heterogeneously. Most importantly, the Sn-Beta catalyst is able to perform the isomerization reaction in highly acidic, aqueous environments with equivalent activity and product distribution as in media without added acid. This enables Sn-Beta to couple isomerizations with other acid-catalyzed reactions, including hydrolysis/isomerization or isomerization/dehydration reaction sequences [starch to fructose and glucose to 5-hydroxymethylfurfural (HMF) demonstrated here]. PMID- 20308578 TI - Transmission distortion by loss of p21 or p27 cyclin-dependent kinase inhibitors following competitive spermatogonial transplantation. AB - Spermatogonial stem cells (SSCs) undergo self-renewal division to support spermatogenesis. Although several positive regulators of SSC self-renewal have been identified, little is known about the mechanisms that negatively regulate SSCs. Here we developed a novel transplantation assay for SSCs and demonstrate that p21 and p27 cyclin-dependent kinase inhibitors play critical roles in SSC self-renewal and differentiation. Overexpression of p21 or p27 abrogated proliferation of cultured SSCs in vitro, and their expression levels were downregulated by exogenous self-renewal signals. In contrast, no apparent defects were found in p21 or p27-deficient SSCs by spermatogonial transplantation. However, competitive spermatogonial transplantation with WT SSCs revealed that the loss of either gene causes distortion of germline transmission: p21 deficiency facilitated mutant offspring production, whereas germline transmission was limited by p27-deficiency. Serial transplantation also showed that the loss of p27, but not p21, decreases secondary colony formation, suggesting that appropriate amounts of p27 are necessary for sustaining SSC self-renewal. Thus, p21 and p27 cyclin-dependent kinase inhibitors play critical roles in germline transmission by regulating the balance between SSC self-renewal and differentiation, and competitive spermatogonial transplantation technique will be useful for analyzing subtle defects in spermatogenesis that are not evident by traditional spermatogonial transplantation. PMID- 20308579 TI - Atomic-level imaging of Mo-V-O complex oxide phase intergrowth, grain boundaries, and defects using HAADF-STEM. AB - In this work, we structurally characterize defects, grain boundaries, and intergrowth phases observed in various Mo-V-O materials using aberration corrected high-angle annular dark-field (HAADF) imaging within a scanning transmission electron microscope (STEM). Atomic-level imaging of these preparations clearly shows domains of the orthorhombic M1-type phase intergrown with the trigonal phase. Idealized models based on HAADF imaging indicate that atomic-scale registry at the domain boundaries can be seamless with several possible trigonal and M1-type unit cell orientation relationships. The alignment of two trigonal domains separated by an M1-type domain or vice versa can be predicted by identifying the number of rows/columns of parallel symmetry operators. Intergrowths of the M1 catalyst with the M2 phase or with the Mo(5)O(14)-type phase have not been observed. The resolution enhancements provided by aberration-correction have provided new insights to the understanding of phase equilibria of complex Mo-V-O materials. This study exemplifies the utility of STEM for the characterization of local structure at crystalline phase boundaries. PMID- 20308580 TI - Neurons sense nanoscale roughness with nanometer sensitivity. AB - The interaction between cells and nanostructured materials is attracting increasing interest, because of the possibility to open up novel concepts for the design of smart nanobiomaterials with active biological functionalities. In this frame we investigated the response of human neuroblastoma cell line (SH-SY5Y) to gold surfaces with different levels of nanoroughness. To achieve a precise control of the nanoroughness with nanometer resolution, we exploited a wet chemistry approach based on spontaneous galvanic displacement reaction. We demonstrated that neurons sense and actively respond to the surface nanotopography, with a surprising sensitivity to variations of few nanometers. We showed that focal adhesion complexes, which allow cellular sensing, are strongly affected by nanostructured surfaces, leading to a marked decrease in cell adhesion. Moreover, cells adherent on nanorough surfaces exhibit loss of neuron polarity, Golgi apparatus fragmentation, nuclear condensation, and actin cytoskeleton that is not functionally organized. Apoptosis/necrosis assays established that nanoscale features induce cell death by necrosis, with a trend directly related to roughness values. Finally, by seeding SH-SY5Y cells onto micropatterned flat and nanorough gold surfaces, we demonstrated the possibility to realize substrates with cytophilic or cytophobic behavior, simply by fine tuning their surface topography at nanometer scale. Specific and functional adhesion of cells occurred only onto flat gold stripes, with a clear self alignment of neurons, delivering a simple and elegant approach for the design and development of biomaterials with precise nanostructure-triggered biological responses. PMID- 20308581 TI - Two competing orientation patterns explain experimentally observed anomalies in growing actin networks. AB - The lamellipodium of migrating animal cells protrudes by directed polymerization of a branched actin network. The underlying mechanisms of filament growth, branching, and capping can be studied in in vitro assays. However, conflicting results have been reported for the force-velocity relation of such actin networks, namely both convex and concave shapes as well as history dependencies. Here we model branching as a reaction that is independent of the number of existing filaments, in contrast to capping, which is assumed to be proportional to the number of existing filaments. Using both stochastic network simulations and deterministic rate equations, we show that such a description naturally leads to the stability of two qualitatively different stationary states of the system, namely a +/- 35 degrees and a +70/0/-70 degrees orientation pattern. Changes in network growth velocity induce a transition between these two patterns. For sufficiently different protrusion efficiency of the two network architectures, this leads to hysteresis in the growth velocity of actin networks under force. Dependent on the history of the system, convex and concave regimes are obtained for the force-velocity relation. Thus a simple generic model can explain the experimentally observed anomalies, with far reaching consequences for cell migration. PMID- 20308582 TI - Subunit interactions in bovine papillomavirus. AB - Papillomaviruses, members of a group of dsDNA viruses associated with epithelial growths and tumors, have compact capsids assembled from 72 pentamers of the protein L1. We have determined the structure of bovine papillomavirus by electron cryomicrosopy (cryoEM), at approximately 3.6 A resolution. The density map, obtained from single-particle analysis of approximately 4,000 particle images, shows the trace of the L1 polypeptide chain and reveals how the N- and C-terminal "arms" of a subunit (extensions from its beta-jelly-roll core) associate with a neighboring pentamer. Critical contacts come from the C-terminal arm, which loops out from the core of the subunit, forms contacts (including a disulfide) with two subunits in a neighboring pentamer, and reinserts into the pentamer from which it emanates. This trace corrects one feature of an earlier model. We discuss implications of the structure for virion assembly and for pathways of infectious viral entry. We suggest that it should be possible to obtain image reconstructions of comparable resolution from cryoEM images of asymmetric particles. From the work on papillomavirus described here, we estimate that such a reconstruction will require about 1.5 million images to achieve the same number of averaged asymmetric units; structural variability will increase this number substantially. PMID- 20308583 TI - Out-of-equilibrium conformational cycling of GroEL under saturating ATP concentrations. AB - The molecular chaperone GroEL exists in at least two allosteric states, T and R, that interconvert in an ATP-controlled manner. Thermodynamic analysis suggests that the T-state population becomes negligible with increasing ATP concentrations, in conflict with the requirement for conformational cycling, which is essential for the operation of molecular machines. To solve this conundrum, we performed fluorescence correlation spectroscopy on the single-ring version of GroEL, using a fluorescent switch recently built into its structure, which turns "on," i.e., increases its fluorescence dramatically, when ATP is added. A series of correlation functions was measured as a function of ATP concentration and analyzed using singular-value decomposition. The analysis assigned the signal to two states whose dynamics clearly differ. Surprisingly, even at ATP saturation, approximately 50% of the molecules still populate the T state at any instance of time, indicating constant out-of-equilibrium cycling between T and R. Only upon addition of the cochaperonin GroES does the T-state population vanish. Our results suggest a model in which the T/R ratio is controlled by the rate of ADP release after hydrolysis, which can be determined accordingly. PMID- 20308584 TI - High-kappa oxide nanoribbons as gate dielectrics for high mobility top-gated graphene transistors. AB - Deposition of high-kappa dielectrics onto graphene is of significant challenge due to the difficulties of nucleating high quality oxide on pristine graphene without introducing defects into the monolayer of carbon lattice. Previous efforts to deposit high-kappa dielectrics on graphene often resulted in significant degradation in carrier mobility. Here we report an entirely new strategy to integrate high quality high-kappa dielectrics with graphene by first synthesizing freestanding high-kappa oxide nanoribbons at high temperature and then transferring them onto graphene at room temperature. We show that single crystalline Al(2)O(3) nanoribbons can be synthesized with excellent dielectric properties. Using such nanoribbons as the gate dielectrics, we have demonstrated top-gated graphene transistors with the highest carrier mobility (up to 23,600 cm(2)/V x s) reported to date, and a more than 10-fold increase in transconductance compared to the back-gated devices. This method opens a new avenue to integrate high-kappa dielectrics on graphene with the preservation of the pristine nature of graphene and high carrier mobility, representing an important step forward to high-performance graphene electronics. PMID- 20308585 TI - Inducible gene expression from the plastid genome by a synthetic riboswitch. AB - Riboswitches are natural RNA sensors that regulate gene expression in response to ligand binding. Riboswitches have been identified in prokaryotes and eukaryotes but are unknown in organelles (mitochondria and plastids). Here we have tested the possibility to engineer riboswitches for plastids (chloroplasts), a genetic system that largely relies on translational control of gene expression. To this end, we have used bacterial riboswitches and modified them in silico to meet the requirements of translational regulation in plastids. These engineered switches were then tested for functionality in vivo by stable transformation of the tobacco chloroplast genome. We report the identification of a synthetic riboswitch that functions as an efficient translational regulator of gene expression in plastids in response to its exogenously applied ligand theophylline. This riboswitch provides a novel tool for plastid genome engineering that facilitates the tightly regulated inducible expression of chloroplast genes and transgenes and thus has wide applications in functional genomics and biotechnology. PMID- 20308586 TI - Combinatorial libraries against libraries for selecting neoepitope activation specific antibodies. AB - A systematic approach to the discovery of conformation-specific antibodies or those that recognize activation-induced neoepitopes in signaling molecules and enzymes will be a powerful tool in developing antibodies for basic science and therapy. Here, we report the isolation of antibody antagonists that preferentially bind activated integrin Mac-1 (alpha(M)beta(2)) and are potent in blocking neutrophil adhesion and migration. A novel strategy was developed for this task, consisting of yeast surface display of Mac-1 inserted (I) domain library, directed evolution to isolate active mutants of the I domain, and screening of phage display of human antibody library against the active I domain in yeast. Enriched antibody library was then introduced into yeast surface two hybrid system for final quantitative selection of antibodies from monomeric antigen-antibody interaction. This led to highly efficient isolation of intermediate to high affinity antibodies, which preferentially reacted with the active I domain, antagonized the I domain binding to intercellular adhesion molecule (ICAM)-1, complement C3 fragment iC3b, and fibronectin, and potently inhibited neutrophil migration on fibrinogen. The strategy demonstrated herein can be broadly applicable to developing antibodies against modular domains that switch between inactive and active conformations, particularly toward the discovery of antibody antagonists in therapeutic and diagnostic applications. PMID- 20308587 TI - p-Adic coupling of mock modular forms and shadows. AB - A "mock modular form" is the holomorphic part of a harmonic Maass form f. The nonholomorphic part of f is a period integral of its "shadow," a cusp form g. A direct method for relating the coefficients of shadows and mock modular forms is not known. We solve these problems when the shadow is an integer weight newform. Our solution is p-adic, and it relies on our definition of an algebraic "regularized mock modular form." As an application, we consider the modular solution to the cubic "arithmetic-geometric mean." PMID- 20308588 TI - Intra- and intercellular fluctuations in Min-protein dynamics decrease with cell length. AB - Self-organization of proteins in space and time is of crucial importance for the functioning of cellular processes. Often, this organization takes place in the presence of strong random fluctuations due to the small number of molecules involved. We report on stochastic switching of the Min-protein distributions between the two cell halves in short Escherichia coli cells. A computational model provides strong evidence that the macroscopic switching is rooted in microscopic noise on the molecular scale. In longer bacteria, the switching turns into regular oscillations that are required for positioning of the division plane. As the pattern becomes more regular, cell-to-cell variability also lessens, indicating cell length-dependent regulation of Min-protein activity. PMID- 20308589 TI - Mapping amorphous calcium phosphate transformation into crystalline mineral from the cell to the bone in zebrafish fin rays. AB - The continuously forming fin bony rays of zebrafish represent a simple bone model system in which mineralization is temporally and spatially resolved. The mineralized collagen fibrils of the fin bones are identical in structure to those found in all known bone materials. We study the continuous mineralization process within the tissue by using synchrotron microbeam x-ray diffraction and small angle scattering, combined with cryo-scanning electron microscopy. The former provides information on the mineral phase and the mineral particles size and shape, whereas the latter allows high-resolution imaging of native hydrated tissues. The integration of the two techniques demonstrates that new mineral is delivered and deposited as packages of amorphous calcium phosphate nanospheres, which transform into platelets of crystalline apatite within the collagen matrix. PMID- 20308590 TI - Compound-specific carbon isotopes from Earth's largest flood basalt eruptions directly linked to the end-Triassic mass extinction. AB - A leading hypothesis explaining Phanerozoic mass extinctions and associated carbon isotopic anomalies is the emission of greenhouse, other gases, and aerosols caused by eruptions of continental flood basalt provinces. However, the necessary serial relationship between these eruptions, isotopic excursions, and extinctions has never been tested in geological sections preserving all three records. The end-Triassic extinction (ETE) at 201.4 Ma is among the largest of these extinctions and is tied to a large negative carbon isotope excursion, reflecting perturbations of the carbon cycle including a transient increase in CO(2). The cause of the ETE has been inferred to be the eruption of the giant Central Atlantic magmatic province (CAMP). Here, we show that carbon isotopes of leaf wax derived lipids (n-alkanes), wood, and total organic carbon from two orbitally paced lacustrine sections interbedded with the CAMP in eastern North America show similar excursions to those seen in the mostly marine St. Audrie's Bay section in England. Based on these results, the ETE began synchronously in marine and terrestrial environments slightly before the oldest basalts in eastern North America but simultaneous with the eruption of the oldest flows in Morocco, a CO(2) super greenhouse, and marine biocalcification crisis. Because the temporal relationship between CAMP eruptions, mass extinction, and the carbon isotopic excursions are shown in the same place, this is the strongest case for a volcanic cause of a mass extinction to date. PMID- 20308591 TI - Lethal protein produced in response to competition between sibling bacterial colonies. AB - Sibling Paenibacillus dendritiformis bacterial colonies grown on low-nutrient agar medium mutually inhibit growth through secretion of a lethal factor. Analysis of secretions reveals the presence of subtilisin (a protease) and a 12 kDa protein, termed sibling lethal factor (Slf). Purified subtilisin promotes the growth and expansion of P. dendritiformis colonies, whereas Slf is lethal and lyses P. dendritiformis cells in culture. Slf is encoded by a gene belonging to a large family of bacterial genes of unknown function, and the gene is predicted to encode a protein of approximately 20 kDa, termed dendritiformis sibling bacteriocin. The 20 kDa recombinant protein was produced and found to be inactive, but exposure to subtilisin resulted in cleavage to the active, 12 kDa form. The experimental results, combined with mathematical modeling, show that subtilisin serves to regulate growth of the colony. Below a threshold concentration, subtilisin promotes colony growth and expansion. However, once it exceeds a threshold, as occurs at the interface between competing colonies, Slf is then secreted into the medium to rapidly reduce cell density by lysis of the bacterial cells. The presence of genes encoding homologs of dendritiformis sibling bacteriocin in other bacterial species suggests that this mechanism for self-regulation of colony growth might not be limited to P. dendritiformis. PMID- 20308592 TI - Genomic arrangement of bacterial operons is constrained by biological pathways encoded in the genome. AB - It is generally known that bacterial genes working in the same biological pathways tend to group into operons, possibly to facilitate cotranscription and to provide stoichiometry. However, very little is understood about what may determine the global arrangement of bacterial genes in a genome beyond the operon level. Here we present evidence that the global arrangement of operons in a bacterial genome is largely influenced by the tendency that a bacterium keeps its operons encoding the same biological pathway in nearby genomic locations, and by the tendency to keep operons involved in multiple pathways in locations close to the other members of their participating pathways. We also observed that the activation frequencies of pathways also influence the genomic locations of their encoding operons, tending to have operons of the more frequently activated pathways more tightly clustered together. We have quantitatively assessed the influences on the global genomic arrangement of operons by different factors. We found that the current arrangements of operons in most of the bacterial genomes we studied tend to minimize the overall distance between consecutive operons of a same pathway across all pathways encoded in the genome. PMID- 20308593 TI - Revealing strengths and weaknesses of methods for gene network inference. AB - Numerous methods have been developed for inferring gene regulatory networks from expression data, however, both their absolute and comparative performance remain poorly understood. In this paper, we introduce a framework for critical performance assessment of methods for gene network inference. We present an in silico benchmark suite that we provided as a blinded, community-wide challenge within the context of the DREAM (Dialogue on Reverse Engineering Assessment and Methods) project. We assess the performance of 29 gene-network-inference methods, which have been applied independently by participating teams. Performance profiling reveals that current inference methods are affected, to various degrees, by different types of systematic prediction errors. In particular, all but the best-performing method failed to accurately infer multiple regulatory inputs (combinatorial regulation) of genes. The results of this community-wide experiment show that reliable network inference from gene expression data remains an unsolved problem, and they indicate potential ways of network reconstruction improvements. PMID- 20308594 TI - Increasing levels of free thyroxine as a risk factor for a first venous thrombosis: a case-control study. AB - A hypercoagulable state exists in hyperthyroidism, but the association with venous thrombosis (VT) is not fully explored. We aimed to investigate VT risk for different plasma levels of thyroid hormones and thyroid antibodies. We used a case-control study on leg vein thrombosis conducted between September 1999 and August 2006 at the Academic Medical Center, Amsterdam, The Netherlands. Parameters of thyroid function were assessed in 190 cases (mean age, 57 years; range, 19-90 years) and 379 sex-matched controls (mean age, 56 years; range, 18 93 years). Odds ratios (ORs) and 95% confidence intervals (CIs) for VT risk were estimated according to several cutoff levels derived from plasma levels observed in controls. We found the risk of VT to gradually rise with increasing levels of free thyroxine (FT(4)). In the absence of traditional acquired risk factors, FT(4) levels above 17 pmol/L yielded a sex- and age-adjusted OR of 2.2 (95% CI, 1.2-4.2) for deep VT, which further increased up to an OR of 13.0 (95% CI, 1.1 154.1) for FT(4) levels above reference range. Our data suggest increasing levels of FT(4) to be a risk factor for VT and may have implications for both the prevention and management of this disease. PMID- 20308595 TI - How I treat hemochromatosis. AB - Hemochromatosis is a common genetic disorder in which iron may progressively accumulate in the liver, heart, and other organs. The primary goal of therapy is iron depletion to normalize body iron stores and to prevent or decrease organ dysfunction. The primary therapy to normalize iron stores is phlebotomy. In this opinion article, we discuss the indications for and monitoring of phlebotomy therapy to achieve iron depletion, maintenance therapy, dietary and pharmacologic maneuvers that could reduce iron absorption, and the role of voluntary blood donation. PMID- 20308596 TI - Activated protein C cofactor function of protein S: a critical role for Asp95 in the EGF1-like domain. AB - Protein S has an established role in the protein C anticoagulant pathway, where it enhances the factor Va (FVa) and factor VIIIa (FVIIIa) inactivating property of activated protein C (APC). Despite its physiological role and clinical importance, the molecular basis of its action is not fully understood. To clarify the mechanism of the protein S interaction with APC, we have constructed and expressed a library of composite or point variants of human protein S, with residue substitutions introduced into the Gla, thrombin-sensitive region (TSR), epidermal growth factor 1 (EGF1), and EGF2 domains. Cofactor activity for APC was evaluated by calibrated automated thrombography (CAT) using protein S-deficient plasma. Of 27 variants tested initially, only one, protein S D95A (within the EGF1 domain), was largely devoid of functional APC cofactor activity. Protein S D95A was, however, gamma-carboxylated and bound phospholipids with an apparent dissociation constant (Kd(app)) similar to that of wild-type (WT) protein S. In a purified assay using FVa R506Q/R679Q, purified protein S D95A was shown to have greatly reduced ability to enhance APC-induced cleavage of FVa Arg306. It is concluded that residue Asp95 within EGF1 is critical for APC cofactor function of protein S and could define a principal functional interaction site for APC. PMID- 20308597 TI - Cross-presentation by dendritic cells from live cells induces protective immune responses in vivo. AB - Cross-presentation is an essential mechanism that allows dendritic cells (DCs) to efficiently present exogenous antigens to CD8(+) T cells. Among cellular antigen sources, apoptotic cells are commonly considered as the best for cross presentation by DCs. However, the potential of live cells as a source of antigen has been overlooked. Here we explored whether DCs were able to capture and cross present antigens from live cells. DCs internalized cytosolic and membrane material into vesicles from metabolically labeled live cells. Using time-lapse confocal microscopy in whole spleens, we showed that DCs internalized material from live cells in vivo. After ovalbumin uptake from live cells, DCs cross-primed ovalbumin-specific naive OT-I CD8(+) T cells in vitro. Injected into mice previously transferred with naive OT-I T cells, they also cross-primed in vivo, even in the absence of endogenous DCs able to present the epitope in the recipient mice. Interestingly, DCs induced stronger natural CD8(+) T-cell responses and protection against a lethal tumor challenge after capture of antigens from live melanoma cells than from apoptotic melanoma cells. The potential for cross-presentation from live cells uncovers a new type of cellular intercommunication and must be taken into account for induction of tolerance or immunity against self, tumors, grafts, or pathogens. PMID- 20308598 TI - The relationship between blood groups and disease. AB - The relative contribution of founder effects and natural selection to the observed distribution of human blood groups has been debated since blood group frequencies were shown to differ between populations almost a century ago. Advances in our understanding of the migration patterns of early humans from Africa to populate the rest of the world obtained through the use of Y chromosome and mtDNA markers do much to inform this debate. There are clear examples of protection against infectious diseases from inheritance of polymorphisms in genes encoding and regulating the expression of ABH and Lewis antigens in bodily secretions particularly in respect of Helicobacter pylori, norovirus, and cholera infections. However, available evidence suggests surviving malaria is the most significant selective force affecting the expression of blood groups. Red cells lacking or having altered forms of blood group-active molecules are commonly found in regions of the world in which malaria is endemic, notably the Fy(a-b-) phenotype and the S-s- phenotype in Africa and the Ge- and SAO phenotypes in South East Asia. Founder effects provide a more convincing explanation for the distribution of the D- phenotype and the occurrence of hemolytic disease of the fetus and newborn in Europe and Central Asia. PMID- 20308599 TI - c-Myc controls the development of CD8alphaalpha TCRalphabeta intestinal intraepithelial lymphocytes from thymic precursors by regulating IL-15-dependent survival. AB - The murine gut epithelium contains a large population of thymus-derived intraepithelial lymphocytes (IELs), including both conventional CD4(+) and CD8alphabeta(+) T cells (expressing T-cell receptor alphabeta [TCRalphabeta]) and unconventional CD8alphaalpha(+) T cells (expressing either TCRalphabeta or TCRgammadelta). Whereas conventional IELs are widely accepted to arise from recirculation of activated CD4(+) and CD8alphabeta(+) T cells from the secondary lymphoid organs to the gut, the origin and developmental pathway of unconventional CD8alphaalpha IELs remain controversial. We show here that CD4-Cre mediated inactivation of c-Myc, a broadly expressed transcription factor with a wide range of biologic activities, selectively impairs the development of CD8alphaalpha TCRalphabeta IELs. In the absence of c-Myc, CD4(-) CD8(-) TCRalphabeta(+) thymic precursors of CD8alphaalpha TCRalphabeta IELs are present but fail to develop on adoptive transfer in immunoincompetent hosts. Residual c Myc-deficient CD8alphaalpha TCRalphabeta IEL display reduced proliferation and increased apoptosis, which correlate with significantly decreased expression of interleukin-15 receptor subunits and lower levels of the antiapoptotic protein Bcl-2. Transgenic overexpression of human BCL-2 resulted in a pronounced rescue of CD8alphaalpha TCRalphabeta IEL in c-Myc-deficient mice. Taken together, our data support a model in which c-Myc controls the development of CD8alphaalpha TCRalphabeta IELs from thymic precursors by regulating interleukin-15 receptor expression and consequently Bcl-2-dependent survival. PMID- 20308600 TI - A unique interaction between alphaIIb and beta3 in the head region is essential for outside-in signaling-related functions of alphaIIbbeta3 integrin. AB - The main interface of the 2 subunits of platelet integrin alphaIIbbeta3 comprises the beta-propeller domain of alphaIIb and the betaA domain of beta3. In the center of the beta-propeller, several aromatic residues interact by cation-pi and hydrophobic bonds with Arg261 of betaA. In this study, we substituted alphaIIb Trp110 or beta3-Arg261 by residues abundant in other alpha or beta subunits at corresponding locations and expressed them in baby hamster kidney cells along with normal beta3 or alphaIIb, respectively. These mutant cells displayed normal surface expression and fibrinogen binding but grossly impaired outside-in signaling-related functions: adhesion to immobilized fibrinogen, cell spreading, focal adhesion kinase phosphorylation, clot retraction, and reduced alphaIIbbeta3 stability in EDTA (ethylenediaminetetraacetic acid). Expression of mutants with substitutions of Arg261 in beta3 by alanine or lysine with normal alphav yielded normal surface expression of alphavbeta3 and soluble fibrinogen binding as well as normal outside-in signaling-related functions, contrasting findings for alphaIIbbeta3. Structural analysis of alphaIIbbeta3 and alphavbeta3 revealed that alphavbeta3 has several strong interactions between alphav and beta3 subunits that are missing in alphaIIbbeta3. Together, these findings indicate that the interaction between Trp110 of alphaIIb and Arg261 of beta3 is critical for alphaIIbbeta3 integrity and outside-in signaling-related functions. PMID- 20308601 TI - Identification during the follow-up of time-dependent prognostic factors for the competing risks of death and blast phase in primary myelofibrosis: a study of 172 patients. AB - The median survival of patients with primary myelofibrosis ranges from 3.5 to 5.5 years, and most patients die from cause related to the disease, including blast phase (BP, in 5%-30% of cases). Because identification of high-risk patients might use information collected during the clinical course, we assessed the prognostic value of time-dependent covariates for 2 competing risks (death and BP) in a series of 172 patients. Significant (P < .01) adverse time-dependent prognostic factors for the risk of death were the time to onset of anemia (hemoglobin < 100 g/L [10 g/dL]), leukocytosis (leukocyte count > 30 x 10(9)/L), thrombocytopenia (platelet count < 150 x 10(9)/L), presence of circulating blasts, intermediate-high or high International Working Group for Myelofibrosis Research and Treatment score, and time to splenectomy. The first 3 dependent covariates and the time to chemotherapy initiation (P = .05) were prognostic factors for the risk of BP. The prognostic effect of onset of leukocytosis was significantly more pronounced for BP than for death. Thus, occurrence during the follow-up of characteristics associated with an adverse prognostic value at diagnosis also influenced the risks of death and BP. Patients with leukocytosis should be closely monitored. These data might efficiently help to evaluate the severity of the disease before treatment decision during the clinical course. PMID- 20308602 TI - Pegylated interferon-alpha, ribavirin, and rituximab combined therapy of hepatitis C virus-related mixed cryoglobulinemia: a long-term study. AB - This study illustrates the use and efficacy of a combination of pegylated interferon-alpha (Peg-IFN-alpha) and ribavirin (RBV), with or without rituximab (RTX), in hepatitis C virus (HCV)-related mixed cryoglobulinemia (MC). Twenty-two patients with HCV-related MC received Peg-IFN-alpha (2a: 180 mug or 2b: 1.5 mug/kg) weekly plus RBV (1000 or 1200 mg) daily for 48 weeks, and RTX (375 mg/m(2)) once a week for 1 month followed by two 5-monthly infusions (termed PIRR). Fifteen additional patients received Peg-IFN-alpha/RBV with the same modalities as the PIRR schedule. Complete response was achieved in 54.5% (12/22) and in 33.3% (5/15) of patients who received PIRR and Peg-IFN-alpha/RBV, respectively (P < .05). Clearance of HCV RNA and conversion of B-cell populations from oligoclonal to polyclonal in liver, bone marrow, and peripheral blood was maintained for up to 3 years in 10 of 12 (83.3%) and in 2 of 5 (40%) patients receiving PIRR and Peg-IFN-alpha/RBV, respectively (P < .01). Cryoproteins in 22.7% (5/22) of patients with PIRR and in 33.3% (5/15) with Peg-IFN-alpha/RBV persisted despite sustained HCV RNA clearance. No response occurred in remaining 5 patients of both groups. PIRR therapy is well tolerated and more effective than Peg-IFN-alpha/RBV combination in HCV-related MC. Its effect may last for more than 3 years. PMID- 20308603 TI - Differential characteristics of Waldenstrom macroglobulinemia according to patterns of familial aggregation. AB - Familial aggregation of Waldenstrom macroglobulinemia (WM) and related B-cell disorders (BCDs) suggests a role for genetic factors, but few data address environmental influences. We designed a questionnaire-based study to examine clinical and environmental factors in a cohort of WM families with various patterns of case aggregation. We analyzed data on 103 WM patients and 272 unaffected relatives from 35 multiple-case WM and 46 mixed WM/BCD kindred and 28 nonfamilial (sporadic) WM patients, using logistic regression models with generalized estimating equations to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for association. In this study population, the WM disease process appeared similar among patients regardless of family history. Familial WM patients were more likely than unaffected relatives to report a history of autoimmune disease (OR, 2.27; 95% CI = 1.21-4.28) and infections (OR, 2.13; 95% CI = 1.25-3.64). Familial WM patients were also more likely to report exposure to farming (OR, 2.70; 95% CI = 1.34-5.42), pesticides (OR, 2.83; 95% CI = 1.56 5.11), wood dust (OR, 2.86; 95% CI = 1.54-5.33), and organic solvents (multiple case WM OR, 4.21; 95% CI = 1.69-10.51) compared with unaffected family members. These data provide clues to both genetic and environmental factors that may influence development of WM. Well-designed case-control studies are needed to confirm these findings. PMID- 20308604 TI - Safety and efficacy of rituximab in patients with hepatitis C virus-related mixed cryoglobulinemia and severe liver disease. AB - The effectiveness of rituximab in hepatitis C virus (HCV)-related mixed cryoglobulinemia (MC) has been shown. However, the risk of an increase in viral replication limits its use in cirrhosis, a condition frequently observed in patients with MC. In this prospective study, 19 HCV-positive patients with MC and advanced liver disease, who were excluded from antiviral therapy, were treated with rituximab and followed for 6 months. MC symptoms included purpura, arthralgias, weakness, sensory-motor polyneuropathy, nephropathy, and leg ulcers. Liver cirrhosis was observed in 15 of 19 patients, with ascitic decompensation in 6 cases. A consistent improvement in MC syndrome was evident at the end-of treatment (EOT) and end-of-follow-up (EOF-U). Variable modifications in both mean viral titers and alanine aminotransferase values were observed at admission, EOT, third month of follow-up, and EOF-U (2.62 x 10(6), 4.28 x 10(6), 4.82 x 10(6), and 2.02 x 10(6) IU/mL and 63.6, 49.1, 56.6, and 51.4 IU/L, respectively). Improvement in liver protidosynthetic activity and ascites degree was observed at EOT and EOF-U, especially in more advanced cases. This study shows the effectiveness and safety of rituximab in MC syndrome with advanced liver disease. Moreover, the depletion of CD20(+) B cells was also followed by cirrhosis syndrome improvement despite the possibility of transient increases of viremia titers. PMID- 20308605 TI - Increased sensitivity to angiotensin II is present postpartum in women with a history of hypertensive pregnancy. AB - Pregnancies complicated by new-onset hypertension are associated with increased sensitivity to angiotensin II, but it is unclear whether this sensitivity persists postpartum. We studied pressor response to infused angiotensin II in 25 normotensive postpartum women in both high- and low-sodium balance. Ten women had a history of hypertensive pregnancy (5 with preeclampsia; 5 with transient hypertension of pregnancy), and 15 women had a history of uncomplicated, normotensive pregnancy. Systolic and diastolic blood pressures, aldosterone, and soluble fms-like tyrosine kinase 1 levels were measured before and after angiotensin II infusion in both dietary phases. In high sodium balance, women with a history of hypertensive pregnancy were normotensive but had significantly higher systolic and diastolic blood pressures than controls (115 versus 104 mm Hg and 73 versus 65 mm Hg, respectively; P<0.05). Women with a history of hypertensive pregnancy had a pressor response to salt loading, demonstrated by an increase in systolic blood pressure on a high-salt diet. They also had greater systolic pressor response (10 versus 2 mm Hg; P=0.03), greater increase in aldosterone (56.8 versus 30.8 ng/dL; P=0.03), and increase in soluble fms-like tyrosine kinase 1 levels (11.0 versus -18.9 pg/mL; P=0.02) after infusion of angiotensin II in low-sodium balance compared with controls. Thus, women with a history of hypertensive pregnancy demonstrated salt sensitivity of blood pressure and had increased pressor, adrenal, and soluble fms-like tyrosine kinase 1 responses to infused angiotensin II in low-sodium balance. Increased sensitivity to angiotensin II observed during pregnancy in women with hypertensive pregnancy is present postpartum; this feature may contribute to future cardiovascular risk in these women. PMID- 20308606 TI - Epidemiology of chronic kidney disease among normotensives: but what is chronic kidney disease? PMID- 20308608 TI - Effect of sodium loading/depletion on renal oxygenation in young normotensive and hypertensive men. AB - The goal of this study was to investigate the effect of sodium intake on renal tissue oxygenation in humans. To this purpose, we measured renal hemodynamics, renal sodium handling, and renal oxygenation in normotensive (NT) and hypertensive (HT) subjects after 1 week of a high-sodium and 1 week of a low sodium diet. Renal oxygenation was measured using blood oxygen level-dependent magnetic resonance. Tissue oxygenation was determined by the measurement of R2* maps on 4 coronal slices covering both kidneys. The mean R2* values in the medulla and cortex were calculated, with a low R2* indicating a high tissue oxygenation. Ten male NT (mean age: 26.5+/-7.4 years) and 8 matched HT subjects (mean age: 28.8+/-5.7 years) were studied. Cortical R2* was not different under the 2 conditions of salt intake. Medullary R2* was significantly lower under low sodium than high sodium in both NT and HT subjects (28.1+/-0.8 versus 31.3+/-0.6 s(-1); P<0.05 in NT; and 27.9+/-1.5 versus 30.3+/-0.8 s(-1); P<0.05, in HT), indicating higher medullary oxygenation under low-sodium conditions. In NT subjects, medullary oxygenation was positively correlated with proximal reabsorption of sodium and negatively with absolute distal sodium reabsorption, but not with renal plasma flow. In HT subjects, medullary oxygenation correlated with the 24-hour sodium excretion but not with proximal or with the distal handling of sodium. These data demonstrate that dietary sodium intake influences renal tissue oxygenation, low sodium intake leading to an increased renal medullary oxygenation both in normotensive and young hypertensive subjects. PMID- 20308607 TI - Prevalence of chronic kidney disease in persons with undiagnosed or prehypertension in the United States. AB - Hypertension is both a cause and a consequence of chronic kidney disease, but the prevalence of chronic kidney disease throughout the diagnostic spectrum of blood pressure has not been established. We determined the prevalence of chronic kidney disease within blood pressure categories in 17 794 adults surveyed by the National Health and Nutrition Examination Survey during 1999-2006. Diagnosed hypertension was defined as self-reported provider diagnosis (n=5832); undiagnosed hypertension was defined as systolic blood pressure > or = 140 mm Hg or diastolic blood pressure > or = 90 mm Hg, without report of provider diagnosis (n=3046); prehypertension was defined as systolic blood pressure > or = 120 and <140 mm Hg or diastolic blood pressure > or = 80 and <90 mm Hg (n=3719); and normal was defined as systolic blood pressure <120 mm Hg and diastolic blood pressure <80 mm Hg (n=5197). Chronic kidney disease was defined as estimated glomerular filtration rate <60 mL/min per 1.73 m(2) or urinary albumin:creatinine ratio >30 mg/g. Prevalences of chronic kidney disease among those with prehypertension and undiagnosed hypertension were 17.3% and 22.0%, respectively, compared with 27.5% with diagnosed hypertension and 13.4% with normal blood pressure, after adjustment for age, sex, and race in multivariable logistic regression. This pattern persisted with varying definitions of kidney disease; macroalbuminuria (urinary albumin:creatinine ratio >300 mg/g) had the strongest association with increasing blood pressure category (odds ratio: 2.37 [95% CI: 2.00 to 2.81]). Chronic kidney disease is prevalent in undiagnosed and prehypertension. Earlier identification and treatment of both these conditions may prevent or delay morbidity and mortality from chronic kidney disease. PMID- 20308609 TI - Endothelial dysfunction and hypertension: cause or effect? PMID- 20308610 TI - Hypoxia-inducible factor prolyl-hydroxylase 2 senses high-salt intake to increase hypoxia inducible factor 1alpha levels in the renal medulla. AB - High salt induces the expression of transcription factor hypoxia-inducible factor (HIF) 1alpha and its target genes in the renal medulla, which is an important renal adaptive mechanism to high-salt intake. HIF prolyl-hydroxylase domain containing proteins (PHDs) have been identified as major enzymes to promote the degradation of HIF-1alpha. PHD2 is the predominant isoform of PHDs in the kidney and is primarily expressed in the renal medulla. The present study tested the hypothesis that PHD2 responds to high salt and mediates high-salt-induced increase in HIF-1alpha levels in the renal medulla. In normotensive rats, high salt intake (4% NaCl, 10 days) significantly inhibited PHD2 expressions and enzyme activities in the renal medulla. Renal medullary overexpression of the PHD2 transgene significantly decreased HIF-1alpha levels. PHD2 transgene also blocked high-salt-induced activation of HIF-1alpha target genes heme oxygenase 1 and NO synthase 2 in the renal medulla. In Dahl salt-sensitive hypertensive rats, however, high-salt intake did not inhibit the expression and activities of PHD2 in the renal medulla. Correspondingly, renal medullary HIF-1alpha levels were not upregulated by high-salt intake in these rats. After transfection of PHD2 small hairpin RNA, HIF-1alpha and its target genes were significantly upregulated by high-salt intake in Dahl salt-sensitive rats. Overexpression of PHD2 transgene in the renal medulla impaired renal sodium excretion after salt loading. These data suggest that high-salt intake inhibits PHD2 in the renal medulla, thereby upregulating the HIF-1alpha expression. The lack of PHD-mediated response to high salt may represent a pathogenic mechanism producing salt-sensitive hypertension. PMID- 20308611 TI - Adenosine activates a2b receptors and enhances chloride secretion in kidney inner medullary collecting duct cells. AB - In the kidney, defects in the regulation of urine salt excretion can result in extracellular fluid volume expansion, leading to salt-sensitive hypertension. Previous studies have demonstrated that, when rats are maintained on a high sodium chloride (NaCl) diet, adenosine production increases in the renal medulla with parallel changes in adenosine receptor expression. These studies suggest that adenosine signaling in the kidney can respond to high NaCl loading; however, the functional consequences of these changes in adenosine signaling are not clear. We used the immortalized cell line mIMCD-K2, a murine model system for the renal inner medullary collecting duct, to study the direct effects of adenosine on NaCl transport across the inner medullary collecting duct epithelium with an Ussing chamber system. When epithelial Na(+) channels were inhibited, the addition of adenosine to the apical side of mIMCD-K2 cell sheets stimulated short circuit current in a dose-dependent manner. This increase in short-circuit current was inhibited by a cystic fibrosis transmembrane conductance regulator Cl(-) channel inhibitor. Pharmacological studies with a panel of adenosine receptor agonists and antagonists demonstrated that adenosine activates apical A2b adenosine receptors to enhance the short-circuit current. Furthermore, adenosine application to mIMCD-K2 cell sheets increased intracellular cAMP, whereas inhibition of protein kinase A completely blocked the adenosine response. Together, our findings indicate that adenosine stimulates Cl(-) secretion through the cystic fibrosis transmembrane conductance regulator in mIMCD-K2 cells by activating apical A2b receptors and signaling through cAMP/protein kinase A. We propose that this adenosine receptor pathway may provide one mechanism for enhancing urine NaCl excretion in the setting of high dietary NaCl intake. PMID- 20308612 TI - Endothelial dysfunction and the risk of hypertension: the multi-ethnic study of atherosclerosis. AB - Hypertension is associated with impaired endothelial function in cross-sectional studies. However, few longitudinal data exist on whether endothelial dysfunction precedes the development of hypertension. We examined the cross-sectional and longitudinal relationships between endothelial-dependent brachial artery flow mediated dilation (FMD) and hypertension prevalence and incidence in 3500 participants from the Multi-Ethnic Study of Atherosclerosis, an ethnically diverse, community-based cohort study. At baseline, the prevalence ratios (95% CI) of hypertension from the highest to the lowest quartile of FMD were 1.00 (referent), 1.26 (1.12 to 1.40), 1.35 (1.21 to 1.52), and 1.68 (1.50 to 1.87; linear trend P<0.001). This association remained (P=0.017) after adjustment for demographics (age, sex, and ethnicity), Multi-Ethnic Study of Atherosclerosis site, and other risk factors. Of the 1869 participants without hypertension at baseline, 584 (31.3%) developed hypertension over a median follow-up of 4.8 years. The unadjusted relative risks (95% CI) of incident hypertension from the highest to the lowest quartile of FMD were 1.00 (referent), 1.38 (1.14 to 1.67), 1.44 (1.19 to 1.74), and 1.64 (1.36 to 1.97; linear trend P<0.001). However, after adjustment for demographics and Multi-Ethnic Study of Atherosclerosis site, the relationship between FMD and incident hypertension was attenuated and not statistically significant: 1.00 (referent), 1.26 (1.04 to 1.52), 1.19 (0.98 to 1.44), and 1.18 (0.97 to 1.44). The longitudinal results also did not appreciably change after adjustment for additional risk factors and baseline blood pressure levels. In this sample, reduced FMD was not an independent predictor of hypertension incidence, suggesting that impaired endothelial function does not play a major role in the development of hypertension. PMID- 20308613 TI - Factor XIIa inhibitor recombinant human albumin Infestin-4 abolishes occlusive arterial thrombus formation without affecting bleeding. AB - BACKGROUND: Blood coagulation is a tightly regulated process of sequentially activated serine proteases culminating in fibrin formation, which is critical for limiting posttraumatic blood loss but also may contribute to acute thrombotic diseases, most notably myocardial infarction and stroke. Recent studies with factor XII-deficient mice revealed that the factor XII-induced intrinsic coagulation pathway is essential for pathological thrombus formation but dispensable for hemostasis. Consequently, these findings led to the hypothesis that factor XII could be a promising pharmacological target for safe antithrombotic therapy. METHODS AND RESULTS: The complementary DNA of the previously described factor XIIa inhibitor Infestin-4, cloned from the midgut of Triatoma infestans, was fused to recombinant human albumin (rHA) and analyzed in vitro. The resulting protein rHA-Infestin-4 specifically inhibits factor XIIa and causes prolonged activated partial thromboplastin time in human, mouse, and rat plasma. To assess its inhibitory potency in vivo, mice and rats were injected with rHA-Infestin-4 and challenged in pathological thrombus formation models. In addition, bleeding assays were performed. rHA-Infestin-4 completely abolished occlusive arterial thrombus formation in mice and rats while leaving hemostasis fully intact. Furthermore, rHA-Infestin-4 was highly protective in a murine model of ischemic stroke. CONCLUSIONS: These results identify rHA-Infestin-4 as a promising agent to achieve powerful protection from ischemic cardiovascular and cerebrovascular events without affecting hemostasis. PMID- 20308614 TI - Early surgery versus conventional treatment in asymptomatic very severe aortic stenosis. AB - BACKGROUND: The optimal timing of surgical intervention remains controversial in asymptomatic patients with very severe aortic stenosis. We therefore compared the long-term results of early surgery and a conventional treatment strategy. METHODS AND RESULTS: From 1996 to 2006, we prospectively included a total of 197 consecutive asymptomatic patients (99 men; age, 63+/-12 years) with very severe aortic stenosis. Patients were excluded if they had angina, syncope, exertional dyspnea, ejection fraction <0.50, significant mitral valve disease, or age >85 years. Very severe aortic stenosis was defined as a critical stenosis in the aortic valve area < or =0.75 cm(2) accompanied by a peak aortic jet velocity > or =4.5 m/s or a mean transaortic pressure gradient > or =50 mm Hg on Doppler echocardiography. The primary end point was defined as the composite of operative mortality and cardiac death during follow-up. Early surgery was performed on 102 patients, and a conventional treatment strategy was used for 95 patients. There were no significant differences between the 2 groups in terms of age, gender, European System for Cardiac Operative Risk Evaluation score, or ejection fraction. During a median follow-up of 1501 days, the operated group had no operative mortalities, no cardiac deaths, and 3 noncardiac deaths; the conventional treatment group had 18 cardiac and 10 noncardiac deaths. The estimated actuarial 6-year cardiac and all-cause mortality rates were 0% and 2+/ 1% in the operated group and 24+/-5% and 32+/-6% in the conventional treatment group, respectively (P<0.001), and for 57 propensity score-matched pairs, the risk of all-cause mortality was significantly lower in the operated group than in the conventional treatment group (hazard ratio, 0.135; 95% confidence interval, 0.030 to 0.597; P=0.008). CONCLUSIONS: Compared with the conventional treatment strategy, early surgery in patients with very severe aortic stenosis is associated with an improved long-term survival by decreasing cardiac mortality. Early surgery is therefore a therapeutic option to further improve clinical outcomes in asymptomatic patients with very severe aortic stenosis and low operative risk. PMID- 20308615 TI - Oxidative stress regulates left ventricular PDE5 expression in the failing heart. AB - BACKGROUND: Phosphodiesterase type 5 (PDE5) inhibition has been shown to exert profound beneficial effects in the failing heart, suggesting a significant role for PDE5 in the development of congestive heart failure (CHF). The purpose of this study is to test the hypothesis that oxidative stress causes increased PDE5 expression in cardiac myocytes and that increased PDE5 contributes to the development of CHF. METHODS AND RESULTS: Myocardial PDE5 expression and cellular distribution were determined in left ventricular samples from patients with end stage CHF and normal donors and from mice after transverse aortic constriction (TAC)-induced CHF. Compared with donor human hearts, myocardial PDE5 protein was increased approximately equal 4.5-fold in CHF samples, and the increase of myocardial PDE5 expression was significantly correlated with myocardial oxidative stress markers 3'-nitrotyrosine or 4-hydroxynonenal expression (P<0.05). Histological examination demonstrated that PDE5 was mainly expressed in vascular smooth muscle in normal donor hearts, but its expression was increased in both cardiac myocytes and vascular smooth muscle of CHF hearts. Myocardial PDE5 protein content and activity also increased in mice after TAC-induced CHF (P<0.05). When the superoxide dismutase (SOD) mimetic M40401 was administered to attenuate oxidative stress, the increased PDE5 protein and activity caused by TAC was blunted, and the hearts were protected against left ventricular hypertrophy and CHF. Conversely, increased myocardial oxidative stress in superoxide dismutase 3 knockout mice caused a greater increase of PDE5 expression and CHF after TAC. In addition, administration of sildenafil to inhibit PDE5 attenuated TAC-induced myocardial oxidative stress, PDE5 expression, and CHF. CONCLUSIONS: Myocardial oxidative stress increases PDE5 expression in the failing heart. Reducing oxidative stress by treatment with M40401 attenuated cardiomyocyte PDE5 expression. This and selective inhibition of PDE5 protected the heart against pressure overload-induced left ventricular hypertrophy and CHF. PMID- 20308616 TI - Evaluation of bromocriptine in the treatment of acute severe peripartum cardiomyopathy: a proof-of-concept pilot study. AB - BACKGROUND: Peripartum cardiomyopathy (PPCM) is a potentially life-threatening heart disease that occurs in previously healthy women. We identified prolactin, mainly its 16-kDa angiostatic and proapoptotic form, as a key factor in PPCM pathophysiology. Previous reports suggest that bromocriptine may have beneficial effects in women with acute onset of PPCM. METHODS AND RESULTS: A prospective, single-center, randomized, open-label, proof-of-concept pilot study of women with newly diagnosed PPCM receiving standard care (PPCM-Std; n=10) versus standard care plus bromocriptine for 8 weeks (PPCM-Br, n=10) was conducted. Because mothers receiving bromocriptine could not breast-feed, the 6-month outcome of their children (n=21) was studied as a secondary end point. Blinded clinical, hemodynamic, and echocardiographic assessments were performed at baseline and 6 months after diagnosis. Cardiac magnetic resonance imaging was performed 4 to 6 weeks after diagnosis in PPCM-Br patients. There were no significant differences in baseline characteristics, including serum 16-kDa prolactin levels and cathepsin D activity, between the 2 study groups. PPCM-Br patients displayed greater recovery of left ventricular ejection fraction (27% to 58%; P=0.012) compared with PPCM-Std patients (27% to 36%) at 6 months. One patient in the PPCM Br group died compared with 4 patients in the PPCM-Std group. Significantly fewer PPCM-Br patients (n=1, 10%) experienced the composite end point of poor outcome defined as death, New York Heart Association functional class III/IV, or left ventricular ejection fraction <35% at 6 months compared with the PPCM-Std patients (n=8, 80%; P=0.006). Cardiac magnetic resonance imaging revealed no intracavitary thrombi. Infants of mothers in both groups showed normal growth and survival. CONCLUSIONS: In this trial, the addition of bromocriptine to standard heart failure therapy appeared to improve left ventricular ejection fraction and a composite clinical outcome in women with acute severe PPCM, although the number of patients studied was small and the results cannot be considered definitive. Larger-scale multicenter and blinded studies are in progress to test this strategy more robustly. PMID- 20308617 TI - Race/ethnicity, quality of care, and outcomes in ischemic stroke. AB - BACKGROUND: Prior studies suggest differences in stroke care associated with race/ethnicity. We sought to determine whether such differences existed in a population of black, Hispanic, and white patients hospitalized with stroke among hospitals participating in a quality-improvement program. METHODS AND RESULTS: We analyzed in-hospital mortality and 7 stroke performance measures among 397,257 patients admitted with ischemic stroke to 1181 hospitals participating in the Get With The Guidelines-Stroke program 2003 through 2008. Relative to white patients, black and Hispanic patients were younger and more often had diabetes mellitus and hypertension. After adjustment for both patient- and hospital-level variables, black patients had lower odds relative to white patients of receiving intravenous thrombolysis (odds ratio [OR], 0.84; 95% confidence interval [CI], 0.77 to 0.91), deep vein thrombosis prophylaxis (OR, 0.88; 95% CI, 0.83 to 0.92), smoking cessation (OR, 0.85; 95% CI, 0.79 to 0.91), discharge antithrombotics (OR, 0.88; 95% CI, 0.84 to 0.92), anticoagulants for atrial fibrillation (OR, 0.84; 95% CI, 0.75 to 0.94), and lipid therapy (OR, 0.91; 95% CI, 0.88 to 0.96), and of dying in-hospital (OR, 0.90; 95% CI, 0.85 to 0.95). Hispanic patients received similar care as their white counterparts on all 7 measures and had similar in-hospital mortality. Black (OR, 1.31; 95% CI, 1.28 to 1.35) and Hispanic (OR, 1.16; 95% CI, 1.11 to 1.20) patients had higher odds of exceeding the median length of hospital stay relative to whites. During the study, quality of care improved in all 3 race/ethnicity groups. CONCLUSIONS: Black patients with stroke received fewer evidence-based care processes than Hispanic or white patients. These differences could lead to increased risk of recurrent stroke. Quality of care improved substantially in the Get With The Guidelines-Stroke Program over time for all 3 racial/ethnic groups. PMID- 20308618 TI - Primary angioplasty versus fibrinolysis in acute myocardial infarction: long-term follow-up in the Danish acute myocardial infarction 2 trial. AB - BACKGROUND: The Danish Acute Myocardial Infarction 2 (DANAMI-2) study found that primary angioplasty (primary percutaneous coronary intervention [pPCI]) compared with fibrinolysis reduced 30-day adverse events in patients with ST-segment elevation myocardial infarction. The present study investigated whether the benefit of pPCI was maintained at a long-term follow-up. METHODS AND RESULTS: We randomly assigned 1572 patients with ST-segment elevation myocardial infarction 1129 patients at referral hospitals and 443 patients at invasive hospitals-to pPCI or fibrinolysis. Median time from randomization to arrival in the catheterization laboratory for patients admitted to referral hospitals was 67 minutes, with 96% of patients arriving in the catheterization laboratory within 120 minutes. The primary study end point was a composite of death or reinfarction. Median follow-up time was 7.8 years. For the primary end point, 8 year cumulative incidence (1-Kaplan-Meier) was 34.8% in the pPCI group and 41.3% in the fibrinolysis group (hazard ratio, 0.78; 95% confidence interval, 0.66 to 0.92). Reinfarction rates were reduced in the pPCI group (11.7% versus 18.5%; hazard ratio, 0.60; 95% confidence interval, 0.46 to 0.77). Among patients randomized at referral hospitals, pPCI reduced reinfarction (13% versus 18.5%; hazard ratio, 0.66; 95% confidence interval, 0.49 to 0.89) and mortality (26.7% versus 33.3%; hazard ratio, 0.78; 95% confidence interval, 0.63 to 0.97). CONCLUSIONS: The benefit of pPCI over fibrinolysis was maintained at a long-term follow-up. pPCI reduced the risk of reinfarction in the overall cohort and reduced reinfarction and mortality among patients randomized at referral hospitals. This result reinforces that pPCI should be offered to ST-segment elevation myocardial infarction patients when interhospital transport to an invasive hospital can be completed within 120 minutes. PMID- 20308619 TI - Medication errors in acute cardiovascular and stroke patients: a scientific statement from the American Heart Association. PMID- 20308620 TI - Bromocriptine for the treatment of peripartum cardiomyopathy. PMID- 20308621 TI - The influence of the maxillary frenum on the development and pattern of dental caries on anterior teeth in breastfeeding infants: prevention, diagnosis, and treatment. AB - In breastfeeding infants, an abnormal attachment of maxillary frenum has the potential to become a significant factor in contributing to facial caries formation on the maxillary anterior teeth. This is in part due to the inability of infants to remove residual milk from the area between the lip and facial surfaces of the maxillary central and lateral incisors at the completion of nursing. Early diagnosis and treatment of an abnormal frenum attachment with the simple and quick revision technique using the Erbium: YAG or Diode laser can prevent these from occurring and does not present any significant risks to the infant. PMID- 20308622 TI - Images in cardiovascular medicine. Fibrinolytic therapy in mechanical valve thrombosis in a one-year-old girl. PMID- 20308623 TI - Letter by Virmani et al regarding article, "Drug-eluting stents in animals and patients: where do we stand today?". PMID- 20308624 TI - Letter by Santangeli et al regarding article, "High-density substrate mapping in Brugada syndrome: combined role of conduction and repolarization heterogeneities in arrhythmogenesis". PMID- 20308627 TI - Global chronic disease research training for fellows: perspectives, challenges, and opportunities. PMID- 20308626 TI - Sugar-sweetened beverages, obesity, type 2 diabetes mellitus, and cardiovascular disease risk. PMID- 20308628 TI - Images in cardiovascular medicine. ST-elevation alternans and nonsustained polymorphic ventricular tachycardia in a patient with Prinzmetal (variant) angina. PMID- 20308629 TI - IFN regulatory factor-1 bypasses IFN-mediated antiviral effects through viperin gene induction. AB - Viperin is an antiviral protein whose expression is highly upregulated during viral infections via IFN-dependent and/or IFN-independent pathways. We examined the molecular alterations induced by the transcriptional activator IFN regulatory factor (IRF)-1 and found viperin to be among the group of IRF-1 regulated genes. From these data, it was not possible to distinguish genes that are primary targets of IRF-1 and those that are targets of IRF-1-induced proteins, like IFN beta. In this study, we show that IRF-1 directly binds to the murine viperin promoter to the two proximal IRF elements and thereby induces viperin expression. Infection studies with embryonal fibroblasts from different gene knock-out mice demonstrate that IRF-1 is essential, whereas the type I IFN system is dispensable for vesicular stomatitis virus induced viperin gene transcription. Further, IRF 1, but not IFN type I, mediates the induction of viperin transcription after IFN gamma treatment. In contrast, IRF-1 is not required for IFN-independent viperin induction by Newcastle disease virus infection and by infection with a vesicular stomatitis virus mutant that is unable to block IFN expression and secretion. We conclude that the IRF-1 mediated type I IFN independent mechanism of enhanced viperin expression provides a redundant mechanism to protect cells from viral infections. This mechanism becomes important when viruses evade innate immunity by antagonizing the induction and function of the IFN system. PMID- 20308630 TI - Treatment failure of a TLR-7 agonist occurs due to self-regulation of acute inflammation and can be overcome by IL-10 blockade. AB - Multiple TLR agonists have been shown to have antitumor effects in animal models. However, the therapeutic efficacy of TLR agonist monotherapy in cancer treatment has been limited, and the mechanisms of failure remain unknown. We demonstrate that topical treatment with a TLR-7 agonist, imiquimod, can elicit significant regression of spontaneous breast cancers in neu transgenic mice, a model of human HER-2/neu(+) breast cancer. However, tumor growth progressed once imiquimod therapy was ended. Gene expression analysis using tumor-derived RNA demonstrated that imiquimod induced high levels of IL-10 in addition to TNF-alpha and IFN gamma. Elevated levels of circulating IL-10 were also detected in sera from imiquimod-treated mice. Elevated serum IL-10 appeared to be derived from IL-10 and dual cytokine secreting (IFN-gamma(+) and IL-10(+)) CD4(+) T cells rather than CD4(+)CD25(+)Foxp3(+) T regulatory cells, which were also induced by imiquimod treatment. Blockade of IL-10, but not TGF-beta, enhanced the antitumor effect of imiquimod by significantly prolonging survival in treated mice. These data suggest that the excessive inflammation induced by TLR agonists may result in a self-regulatory immunosuppression via IL-10 induction and that blocking IL 10 could enhance the therapeutic efficacy of these agents. PMID- 20308631 TI - B cell-derived vascular endothelial growth factor A promotes lymphangiogenesis and high endothelial venule expansion in lymph nodes. AB - Vascular endothelial growth factor A (VEGF-A) is a prominent growth factor for both angiogenesis and lymphangiogenesis. Recent studies have shown the importance of VEGF-A in enhancing the growth of lymphatic endothelial cells in lymph nodes (LNs) and the migration of dendritic cells into LNs. VEGF-A is produced in inflamed tissues and/or in draining LNs, where B cells are a possible source of this growth factor. To study the effect of B cell-derived VEGF-A, we created transgenic mice (CD19(Cre)/hVEGF-A(fl)) that express human VEGF-A specifically in B cells. We found that the human VEGF-A produced by B cells not only induced lymphangiogenesis in LNs, but also induced the expansion of LNs and the development of high endothelial venules. Contrary to our expectation, we observed a significant decrease in the Ag-specific Ab production postimmunization with OVA and in the proinflammatory cytokine production postinoculation with LPS in these mice. Our findings suggest immunomodulatory effects of VEGF-A: B cell-derived VEGF-A promotes both lymphangiogenesis and angiogenesis within LNs, but then suppresses certain aspects of the ensuing immune responses. PMID- 20308632 TI - The effector T cell response to ryegrass pollen is counterregulated by simultaneous induction of regulatory T cells. AB - Allergy is associated with pathological Th2 responses to otherwise harmless environmental Ags. In contrast, nonallergic individuals mount nonpathological immune responses to allergens, partly attributed to regulatory T cell (Treg) activity. Although thymus-derived natural Tregs have been shown to maintain tolerance to self-Ags and prevent autoimmunity, the generation of Tregs specific to non-self-Ags is less well understood. We investigated the potential for induction of Tregs from PBMCs of ryegrass pollen-allergic or healthy subjects by stimulation in vitro with ryegrass pollen extract in the absence of additional exogenous stimuli. We found that two subsets of proliferating CD4(+) T cells were induced, one expressing intermediate levels of Foxp3 (and IFN-gamma, IL-4, IL-17, or IL-2) and the other expressing high levels of Foxp3 (and no effector cytokines). After enrichment based on CD39 expression, the Foxp3(hi) subset suppressed CD4(+) T cell proliferation and IFN-gamma production. The Foxp3(hi) Treg originated from both conversion of dividing non-Tregs (CD4(+)CD25( )CD127(hi)) and expansion of natural Tregs (CD4(+)CD25(+)CD127(lo)). Stable functional Tregs expressing high levels of Foxp3 were induced simultaneously with effector T cells by allergen stimulation. Induction of Foxp3(hi) Tregs was reduced in allergic subjects. These results indicate that the cogeneration of Foxp3(hi) Tregs in response to allergen may be a mechanism for controlling allergic reactions in healthy individuals, which is impaired in those with allergies. PMID- 20308633 TI - Cutting edge: IL-23 receptor deficiency prevents the development of lupus nephritis in C57BL/6-lpr/lpr mice. AB - IL-17-producing T cells infiltrate kidneys of patients with lupus nephritis, and IL-23-treated lymph node cells from lupus-prone mice may transfer disease to Rag1 deficient mice. In this study, we show that IL-23R-deficient lupus-prone C57BL/6 lpr/lpr mice display decreased numbers of CD3(+)CD4(-)CD8(-) cells and IL-17A producing cells in the lymph nodes and produce less anti-DNA Abs. In addition, clinical and pathology measures of lupus nephritis are abrogated. The presented experiments document the importance of IL-23R-mediated signaling in the development of lupus nephritis and urge the consideration of proper biologics for the treatment of the disease. PMID- 20308634 TI - Histone acetylation at the single-cell level: a marker of memory CD8+ T cell differentiation and functionality. AB - Following stimulation, memory T (T(M)) cells rapidly express many effector functions, a hallmark feature that allows them to provide protective immunity. Recent studies suggest that genes involved in this rapid recall response may maintain an open chromatin structure in resting T(M) cells via epigenetic modifications. However, these studies have mostly focused on a few loci, and the techniques used required a large number of cells. We have developed a flow cytometric assay measuring histone modifications in individual murine T cells in combination with lineage-specific markers. In this study, we show that the per cell level of a marker of open chromatin, diacetylated histone H3 (diAcH3), increases as naive CD8(+) T cells develop into T(M) cells, demonstrating a novel correlation between the differentiation state of a CD8(+) T cell and its abundance of a specific histone modification. Furthermore, our results show that T(M) cells defective in rapid recall ability have less diAcH3 than their fully functional counterparts, indicating that the diAcH3 level of individual T(M) cells is a useful marker for assessing their functionality. PMID- 20308635 TI - Functional analysis of Lyn kinase A and B isoforms reveals redundant and distinct roles in Fc epsilon RI-dependent mast cell activation. AB - Engagement of FcepsilonRI causes its phosphorylation by Lyn kinase. Two alternatively spliced variants, Lyn A and B, are expressed in mast cells, and both isoforms interact with FcepsilonRI. Unlike Lyn A, Lyn B lacks a 21-aa region in the N-terminal unique domain. In this study, we investigated the role of Lyn A and B isoforms in mast cell signaling and responses. Lyn B was found to be a poor inducer of mast cell degranulation and was less potent in both inositol 1,4,5 triphosphate production and calcium responses. Expression of Lyn B alone showed reduced phosphorylation of both phospholipase Cgamma-1 and -2 and decreased interaction of phospholipase Cgamma-1 with the phosphorylated linker for activation of T cells. Lyn B also showed increased binding of tyrosine phosphorylated proteins, which included the negative regulatory lipid phosphatase SHIP-1. In contrast, both Lyn A and B caused similar total cellular tyrosine phosphorylation and FcepsilonRI phosphorylation and neither Lyn A nor Lyn B alone could completely restore mast cell degranulation or dampen the excessive cytokine production seen in the absence of Lyn. However, expression of both isoforms showed complementation and normalized responses. These findings demonstrate that Lyn B differs from Lyn A in its association with SHIP-1 and in the regulation of calcium responses. However, complementation of both isoforms is required in mast cell activation. PMID- 20308636 TI - Genome-wide mapping and assembly of structural variant breakpoints in the mouse genome. AB - Structural variation (SV) is a rich source of genetic diversity in mammals, but due to the challenges associated with mapping SV in complex genomes, basic questions regarding their genomic distribution and mechanistic origins remain unanswered. We have developed an algorithm (HYDRA) to localize SV breakpoints by paired-end mapping, and a general approach for the genome-wide assembly and interpretation of breakpoint sequences. We applied these methods to two inbred mouse strains: C57BL/6J and DBA/2J. We demonstrate that HYDRA accurately maps diverse classes of SV, including those involving repetitive elements such as transposons and segmental duplications; however, our analysis of the C57BL/6J reference strain shows that incomplete reference genome assemblies are a major source of noise. We report 7196 SVs between the two strains, more than two-thirds of which are due to transposon insertions. Of the remainder, 59% are deletions (relative to the reference), 26% are insertions of unlinked DNA, 9% are tandem duplications, and 6% are inversions. To investigate the origins of SV, we characterized 3316 breakpoint sequences at single-nucleotide resolution. We find that approximately 16% of non-transposon SVs have complex breakpoint patterns consistent with template switching during DNA replication or repair, and that this process appears to preferentially generate certain classes of complex variants. Moreover, we find that SVs are significantly enriched in regions of segmental duplication, but that this effect is largely independent of DNA sequence homology and thus cannot be explained by non-allelic homologous recombination (NAHR) alone. This result suggests that the genetic instability of such regions is often the cause rather than the consequence of duplicated genomic architecture. PMID- 20308637 TI - B-type natriuretic peptide-guided heart failure therapy: A meta-analysis. AB - BACKGROUND: The use of plasma levels of B-type natriuretic peptides (BNPs) to guide treatment of patients with chronic heart failure (HF) has been investigated in a number of randomized controlled trials (RCTs). However, the benefits of this treatment approach have been uncertain. We therefore performed a meta-analysis to examine the overall effect of BNP-guided drug therapy on cardiovascular outcomes in patients with chronic HF. METHODS: We identified RCTs by systematic search of manuscripts, abstracts, and databases. Eligible RCTs were those that enrolled more than 20 patients and involved comparison of BNP-guided drug therapy vs usual clinical care of the patient with chronic HF in an outpatient setting. RESULTS: Eight RCTs with a total of 1726 patients and with a mean duration of 16 months (range, 3-24 months) were included in the meta-analysis. Overall, there was a significantly lower risk of all-cause mortality (relative risk [RR], 0.76; 95% confidence interval [CI], 0.63-0.91; P = .003) in the BNP-guided therapy group compared with the control group. In the subgroup of patients younger than 75 years, all-cause mortality was also significantly lower in the BNP-guided group (RR, 0.52; 95% CI, 0.33-0.82; P = .005). However, there was no reduction in mortality with BNP-guided therapy in patients 75 years or older (RR, 0.94; 95% CI, 0.71-1.25; P = .70). The risk of all-cause hospitalization and survival free of any hospitalization was not significantly different between groups (RR, 0.82; 95% CI, 0.64-1.05; P = .12 and RR, 1.07; 95% CI, 0.85-1.34; P = .58, respectively). The additional percentage of patients achieving target doses of angiotensin-converting enzyme inhibitors and beta-blockers during the course of these trials averaged 21% and 22% in the BNP group and 11.7% and 12.5% in the control group, respectively. CONCLUSIONS: B-type natriuretic peptide-guided therapy reduces all-cause mortality in patients with chronic HF compared with usual clinical care, especially in patients younger than 75 years. A component of this survival benefit may be due to increased use of agents proven to decrease mortality in chronic HF. However, there does not seem to be a reduction in all cause hospitalization or an increase in survival free of hospitalization using this approach. PMID- 20308638 TI - Covering cancer: comment on "cancer and the media". PMID- 20308640 TI - Substitution of (R,S)-methadone by (R)-methadone: Impact on QTc interval. AB - BACKGROUND: Methadone is administered as a chiral mixture of (R,S)-methadone. The opioid effect is mainly mediated by (R)-methadone, whereas (S)-methadone blocks the human ether-a-go-go-related gene (hERG) voltage-gated potassium channel more potently, which can cause drug-induced long QT syndrome, leading to potentially lethal ventricular tachyarrhythmias. METHODS: To investigate whether substitution of (R,S)-methadone by (R)-methadone could reduce the corrected QT (QTc) interval, (R,S)-methadone was replaced by (R)-methadone (half-dose) in 39 opioid-dependent patients receiving maintenance treatment for 14 days. (R)-methadone was then replaced by the initial dose of (R,S)-methadone for 14 days (n = 29). Trough (R) methadone and (S)-methadone plasma levels and electrocardiogram measurements were taken. RESULTS: The Fridericia-corrected QT (QTcF) interval decreased when (R,S) methadone was replaced by a half-dose of (R)-methadone; the median (interquartile range [IQR]) values were 423 (398-440) milliseconds (ms) and 412 (395-431) ms (P = .06) at days 0 and 14, respectively. Using a univariate mixed-effect linear model, the QTcF value decreased by a mean of -3.9 ms (95% confidence interval [CI], -7.7 to -0.2) per week (P = .04). The QTcF value increased when (R) methadone was replaced by the initial dose of (R,S)-methadone for 14 days; median (IQR) values were 424 (398-436) ms and 424 (412-443) ms (P = .01) at days 14 and 28, respectively. The univariate model showed that the QTcF value increased by a mean of 4.7 ms (95% CI, 1.3-8.1) per week (P = .006). CONCLUSIONS: Substitution of (R,S)-methadone by (R)-methadone reduces the QTc interval value. A safer cardiac profile of (R)-methadone is in agreement with previous in vitro and pharmacogenetic studies. If the present results are confirmed by larger studies, (R)-methadone should be prescribed instead of (R,S)-methadone to reduce the risk of cardiac toxic effects and sudden death. PMID- 20308641 TI - Bupropion and cognitive behavioral therapy for weight-concerned women smokers. AB - BACKGROUND: We previously documented that cognitive behavioral therapy for smoking-related weight concerns (CONCERNS) improves cessation rates. However, the efficacy of combining CONCERNS with cessation medication is unknown. We sought to determine if the combination of CONCERNS and bupropion therapy would enhance abstinence for weight-concerned women smokers. METHODS: In a randomized, double blind, placebo-controlled trial, weight-concerned women (n = 349; 86% white) received smoking cessation counseling and were randomized to 1 of 2 adjunctive counseling components: CONCERNS or STANDARD (standard cessation treatment with added discussion of smoking topics but no specific weight focus), and 1 of 2 medication conditions: bupropion hydrochloride sustained release (B) or placebo (P) for 6 months. Rates and duration of biochemically verified prolonged abstinence were the primary outcomes. Point-prevalent abstinence, postcessation weight gain, and changes in nicotine withdrawal, depressive symptoms, and weight concerns were evaluated. RESULTS: Women in the CONCERNS + B group had higher rates of abstinence (34.0%) and longer time to relapse than did those in the STANDARD + B (21%; P = .05) or CONCERNS + P (11.5%; P = .005) groups at 6 months, although rates of prolonged abstinence in the CONCERNS + B and STANDARD + B groups did not differ significantly at 12 months. Abstinence rates and duration did not differ in the STANDARD + B group (21% and 19%) compared with the STANDARD + P group (10% and 7%) at 6 and 12 months, respectively. There were no differences among abstinent women in postcessation weight gain or weight concerns, although STANDARD + B produced greater decreases in nicotine withdrawal and depressive symptoms than did STANDARD + P. CONCLUSIONS: Weight-concerned women smokers receiving the combination of CONCERNS + B were most likely to sustain abstinence. This effect was not related to differences in postcessation weight gain or changes in weight concerns. Trial Registration clinicaltrials.gov Identifier: NCT00006170. PMID- 20308643 TI - Trends in chronic obstructive pulmonary disease prevalence, incidence, and mortality in ontario, Canada, 1996 to 2007: a population-based study. AB - BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a preventable and treatable disease with a prevalence of more than 10% worldwide among adults 40 years and older. Whether this amount has been increasing, decreasing, or stable over time remains unknown. METHODS: A longitudinal cohort study using population based, health administrative data from 1991 to 2007 was conducted in Ontario, Canada. Individuals with COPD were identified using a previously validated health administrative case definition of COPD. Annual COPD prevalence, incidence, and all-cause mortality rates were estimated from 1996 to 2007. RESULTS: The prevalence of COPD increased by 64.8% between 1996 and 2007. The age- and sex standardized COPD prevalence rate increased from 7.8% to 9.5%, representing a relative increase of 23.0% (P < .001). The age- and sex-standardized incidence decreased from 11.8 per 1000 adults to 8.5 per 1000 adults, representing a relative decrease of 28.3% (P < .001). Finally, the age- and sex-standardized all cause mortality rate decreased from 5.7% to 4.3%, representing a relative decrease of 24.0% (P < .001). CONCLUSIONS: Our findings indicate a substantial increase in COPD prevalence in the last decade, with more of the burden being shifted from men to women. Effective clinical and public health strategies are needed to prevent COPD and manage the increasing number of people living longer with this disease. PMID- 20308642 TI - Curbing methicillin-resistant Staphylococcus aureus in 38 French hospitals through a 15-year institutional control program. AB - BACKGROUND: The Assistance Publique-Hopitaux de Paris (AP-HP) institution administers 38 teaching hospitals (23 acute care and 15 rehabilitation and long term care hospitals; total, 23 000 beds) scattered across Paris and surrounding suburbs in France. In the late 1980s, the proportion of methicillin resistance among clinical strains of Staphylococcus aureus (MRSA) reached approximately 40% at AP-HP. METHODS: A program aimed at curbing the MRSA burden was launched in 1993, based on passive and active surveillance, barrier precautions, training, and feedback. This program, supported by the strong commitment of the institution, was reinforced in 2001 by a campaign promoting the use of alcohol based hand-rub solutions. An observational study on MRSA rate was prospectively carried out from 1993 onwards. RESULTS: There was a significant progressive decrease in MRSA burden (-35%) from 1993 to 2007, whether recorded as the proportion (expressed as percentage) of MRSA among S aureus strains (41.0% down to 26.6% overall; 45.3% to 24.2% in blood cultures) or incidence of MRSA cases (0.86 down to 0.56 per 1000 hospital days). The MRSA burden decreased more markedly in intensive care units (-59%) than in surgical (-44%) and medical ( 32%) wards. The use of ABHR solutions (in liters per 1000 hospital days) increased steadily from 2 L to 21 L (to 26 L in acute care hospitals and to 10 L in rehabilitation and long-term care hospitals) following the campaign. CONCLUSION: A sustained reduction of MRSA burden can be obtained at the scale of a large hospital institution with high endemic MRSA rates, providing that an intensive program is maintained for a long period. PMID- 20308644 TI - Individualized medical decision making: necessary, achievable, but not yet attainable. AB - The need is urgent to provide older persons with individualized information about the benefits and harms of different diagnostic and treatment strategies. This need results from the growing recognition of the heterogeneity in outcomes in older persons with differing comorbidity profiles. The heterogeneity of benefits and harms resulting from treatment is not yet as well appreciated. Warfarin vs aspirin therapy for the reduction of stroke risk in nonvalvular atrial fibrillation provides an example of a treatment for which the benefit-to-harm ratio may actually reverse according to an older person's comorbidities, thus highlighting the importance of basing this treatment decision on individualized outcome data. Despite the wealth of studies in nonvalvular atrial fibrillation, many assumptions are necessary to calculate patient-specific outcomes, and these assumptions may lead to substantial overestimation or underestimation of benefits and harms. Improving care for patients with comorbidities will require substantive increases in the efforts and resources allocated to the collection and dissemination of outcome data for patients with varying comorbidities. PMID- 20308645 TI - The socioeconomic gradient in daily colds and influenza, headaches, and pain. PMID- 20308646 TI - Vitamin D supplementation. PMID- 20308647 TI - Evaluating enzyme replacement therapy in fabry disease. PMID- 20308649 TI - Re: Late effects from radiation therapy: the hits just keep on coming. PMID- 20308648 TI - Association between a germline OCA2 polymorphism at chromosome 15q13.1 and estrogen receptor-negative breast cancer survival. AB - BACKGROUND: Traditional prognostic factors for survival and treatment response of patients with breast cancer do not fully account for observed survival variation. We used available genotype data from a previously conducted two-stage, breast cancer susceptibility genome-wide association study (ie, Studies of Epidemiology and Risk factors in Cancer Heredity [SEARCH]) to investigate associations between variation in germline DNA and overall survival. METHODS: We evaluated possible associations between overall survival after a breast cancer diagnosis and 10 621 germline single-nucleotide polymorphisms (SNPs) from up to 3761 patients with invasive breast cancer (including 647 deaths and 26 978 person-years at risk) that were genotyped previously in the SEARCH study with high-density oligonucleotide microarrays (ie, hypothesis-generating set). Associations with all-cause mortality were assessed for each SNP by use of Cox regression analysis, generating a per rare allele hazard ratio (HR). To validate putative associations, we used patient genotype information that had been obtained with 5' nuclease assay or mass spectrometry and overall survival information for up to 14 096 patients with invasive breast cancer (including 2303 deaths and 70 019 person years at risk) from 15 international case-control studies (ie, validation set). Fixed-effects meta-analysis was used to generate an overall effect estimate in the validation dataset and in combined SEARCH and validation datasets. All statistical tests were two-sided. RESULTS: In the hypothesis-generating dataset, SNP rs4778137 (C>G) of the OCA2 gene at 15q13.1 was statistically significantly associated with overall survival among patients with estrogen receptor-negative tumors, with the rare G allele being associated with increased overall survival (HR of death per rare allele carried = 0.56, 95% confidence interval [CI] = 0.41 to 0.75, P = 9.2 x 10(-5)). This association was also observed in the validation dataset (HR of death per rare allele carried = 0.88, 95% CI = 0.78 to 0.99, P = .03) and in the combined dataset (HR of death per rare allele carried = 0.82, 95% CI = 0.73 to 0.92, P = 5 x 10(-4)). CONCLUSION: The rare G allele of the OCA2 polymorphism, rs4778137, may be associated with improved overall survival among patients with estrogen receptor-negative breast cancer. PMID- 20308650 TI - Conventional and complementary therapies: a tale of two research standards? PMID- 20308651 TI - Cancer in the oldest old: making better treatment decisions. PMID- 20308652 TI - Therapy for recurrent high-grade gliomas: does continuous dose-intense temozolomide have a role? PMID- 20308653 TI - Role of fusion subtype in Ewing sarcoma. PMID- 20308654 TI - TP53 alterations determine clinical subgroups and survival of patients with choroid plexus tumors. AB - PURPOSE Choroid plexus carcinomas are pediatric tumors with poor survival rates and a strong, but poorly understood, association with Li-Fraumeni syndrome (LFS). Currently, with lack of biologic predictors, most children are treated with aggressive chemoradiation protocols. PATIENTS AND METHODS We established a multi institutional tissue and clinical database, which enabled the analysis of specific alterations of the TP53 tumor suppressor and its modifiers in choroid plexus tumors (CPTs). We conducted high-resolution copy-number analysis to correlate these genetic parameters with family history and outcome. Results We studied 64 patients with CPTs. All individuals with germline TP53 mutations fulfilled LFS criteria, whereas all patients not meeting these criteria harbored wild-type TP53 (P < .001). TP53 mutations were found in 50% of choroid plexus carcinomas (CPCs). Additionally, two sequence variants known to confer TP53 dysfunction, TP53 codon72 and MDM2 SNP309, coexisted in the majority of TP53 wild type CPCs (92%) and not in TP53 mutated CPC (P = .04), which suggests a complementary mechanism of TP53 dysfunction in the absence of a TP53 mutation. High-resolution single nucleotide polymorphism (SNP) array analysis revealed extremely high total structural variation (TSV) in TP53-mutated CPC tumor genomes compared with TP53 wild-type tumors and choroid plexus papillomas (CPPs; P = .006 and .004, respectively). Moreover, high TSV was associated with significant risk of progression (P < .001). Five-year survival rates for patients with TP53 immunopositive and -immunonegative CPCs were 0% and 82 (+/- 9%), respectively (P < .001). Furthermore, 14 of 16 patients with TP53 wild-type CPCs are alive without having received radiation therapy. CONCLUSION Patients with CPC who have low tumor TSV and absence of TP53 dysfunction have a favorable prognosis and can be successfully treated without radiation therapy. PMID- 20308655 TI - Phase II trial of continuous dose-intense temozolomide in recurrent malignant glioma: RESCUE study. AB - PURPOSE Concomitant temozolomide (TMZ)/radiotherapy followed by adjuvant TMZ has increased survival in patients with glioblastoma multiforme (GBM). However, few options are effective for patients who experience treatment failure. We conducted a multicenter, phase II study to assess the efficacy and safety of continuous dose-intense TMZ for recurrent GBM. PATIENTS AND METHODS Patients with malignant glioma at progression after standard TMZ 150 to 200 mg/m(2) x 5 days in a 28-day cycle for three or more cycles were stratified by tumor type (anaplastic glioma group A, GBM, group B). Ninety-one patients with GBM were prospectively divided into three groups (early [B1], extended [B2], and rechallenge [B3]) according to the timing of progression during adjuvant therapy. All patients received continuous dose-intense TMZ 50 mg/m(2)/d for up to 1 year or until progression occurred. Response was assessed by using RECIST (Response Evaluation Criteria in Solid Tumors). Results A total of 116 of 120 patients were evaluable for efficacy. For patients with GBM, 6-month progression-free survival (PFS) was 23.9% (B1, 27.3%; B2, 7.4%; B3, 35.7%). One-year survival from time of study entry was 27.3%, 14.8%, and 28.6% for the B1, B2 and B3 groups, respectively. For patients with anaplastic glioma, 6-month PFS was 35.7%; 1-year survival was 60.7%. The most common grades 3 and 4 nonhematologic toxicities were nausea/vomiting (6.7%) and fatigue (5.8%). Grades 3 and 4 hematologic toxicities were uncommon. CONCLUSION Rechallenge with continuous dose-intense TMZ 50 mg/m(2)/d is a valuable therapeutic option for patients with recurrent GBM. Patients who experience progression during the first six cycles of conventional adjuvant TMZ therapy or after a treatment-free interval get the most benefit from therapy. PMID- 20308656 TI - High EVI1 expression predicts outcome in younger adult patients with acute myeloid leukemia and is associated with distinct cytogenetic abnormalities. AB - PURPOSE The purpose of this study was to investigate frequency and prognostic significance of high EVI1 expression in acute myeloid leukemia (AML). PATIENTS AND METHODS A diagnostic assay detecting multiple EVI1 splice variants was developed to determine the relative EVI1 expression by single real-time quantitative polymerase chain reaction in 1,382 newly diagnosed adult patients with AML younger than 60 years. Patients were treated on four Dutch-Belgian HOVON (n = 458) and two German-Austrian AML Study Group protocols (n = 924). Results The EVI1 assay was tested in the HOVON cohort and validated in the AMLSG cohort. High EVI1 levels (EVI1(+)) were found with similar frequencies in both cohorts combined, with a 10.7% incidence (148 of 1,382). EVI1(+) independently predicted low complete remission (CR) rate (odds ratio, 0.54; P = .002), adverse relapse free survival (RFS; hazard ratio [HR], 1.32; P = .05), and event-free survival (EFS; HR, 1.46; P < .001). This adverse prognostic impact was more pronounced in the intermediate cytogenetic risk group (EFS; HR, 1.64; P < .001; and RFS; HR, 1.55; P = .02), and was also apparent in cytogenetically normal AML (EFS; HR, 1.67; P = .008). Besides inv(3)/t(3;3), EVI1(+) was significantly associated with chromosome abnormalities monosomy 7 and t(11q23), conferring prognostic impact within these two cytogenetic subsets. EVI1(+) was virtually absent in favorable risk AML and AML with NPM1 mutations. Patients with EVI1(+) AML (n = 28) who received allogeneic stem cell transplantation in first CR had significantly better 5-year RFS (33% +/- 10% v 0%). CONCLUSION EVI1 expression in AML is unequally distributed in cytogenetic subtypes. It predicts poor outcome, particularly among intermediate cytogenetic risk AML. Patients with EVI1(+) AML may benefit from allogeneic transplantation in first CR. Pretreatment EVI1 screening should be included in risk stratification. PMID- 20308657 TI - Detecting disabilities in older patients with cancer: comparison between comprehensive geriatric assessment and vulnerable elders survey-13. AB - PURPOSE Comprehensive geriatric assessment (CGA) is a multidimensional method used by geriatricians and oncologists to detect and evaluate multiple age-related problems and to plan and coordinate interventions. Because its main drawback is the time required, efforts have been made to evaluate screening instruments suitable for preliminarily assessing elderly patients. The main aim of this study was to establish the accuracy of the Vulnerable Elders Survey-13 (VES-13) in predicting the presence of abnormalities revealed by CGA. PATIENTS AND METHODS Patients age > or = 70 years with a histologically or cytologically confirmed diagnosis of a solid or hematologic tumor underwent both CGA and a VES-13 assessment, and the reliability and validity of VES-13 were analyzed. Results Fifty-three percent of the 419 elderly patients with cancer (mean age, 76.8 years) were vulnerable on VES-13; the rates of disabilities on CGA and activities of daily living (ADLs)/instrumental activities of daily living (IADLs) scales were 30% and 25%, respectively. The sensitivity and specificity of VES-13 were 87% and 62%, respectively, versus CGA and 90% and 70%, respectively, versus ADL/IADL scales. CONCLUSIONS On the basis of our data, VES-13 is highly predictive of impaired functional status and can thus be considered a useful preliminary means of assessing older patients with cancer before undertaking a full CGA. PMID- 20308658 TI - Breast cancer among the oldest old: tumor characteristics, treatment choices, and survival. AB - PURPOSE Few data are available on breast cancer characteristics, treatment, and survival for women age 80 years or older. PATIENTS AND METHODS We used the linked Surveillance, Epidemiology and End Results-Medicare data set from 1992 to 2003 to examine tumor characteristics, treatments (mastectomy, breast-conserving surgery [BCS] with radiation therapy or alone, or no surgery), and outcomes of women age 80 years or older (80 to 84, 85 to 89, > or = 90 years) with stage I/II breast cancer compared with younger women (age 67 to 79 years). We used Cox proportional hazard models to examine the impact of age on breast cancer-related and other causes of death. Analyses were performed within stage, adjusted for tumor and sociodemographic characteristics, treatments received, and comorbidities. Results In total, 49,616 women age 67 years or older with stage I/II disease were included. Tumor characteristics (grade, hormone receptivity) were similar across age groups. Treatment with BCS alone increased with age, especially after age 80. The risk of dying from breast cancer increased with age, significantly after age 80. For stage I disease, the adjusted hazard ratio of dying from breast cancer for women age > or = 90 years compared with women age 67 to 69 years was 2.6 (range, 2.0 to 3.4). Types of treatments received were significantly associated with age and comorbidity, with age as the stronger predictor (26% of women age > or = 80 years without comorbidity received BCS alone or no surgery compared with 6% of women age 67 to 79 years). CONCLUSION Women age > or = 80 years have breast cancer characteristics similar to those of younger women yet receive less aggressive treatment and experience higher mortality from early-stage breast cancer. Future studies should focus on identifying tumor and patient characteristics to help target treatments to the oldest women most likely to benefit. PMID- 20308659 TI - Irinotecan in the adjuvant treatment of colon cancer: is the story finished or does personalized therapy open new opportunities? PMID- 20308660 TI - Palliative chemoradiation in advanced hepatocellular carcinoma. PMID- 20308662 TI - Child with ataxia telangiectasia developing acute myeloid leukemia. PMID- 20308661 TI - Multidisciplinary meeting on male breast cancer: summary and research recommendations. AB - Male breast cancer is a rare disease, accounting for less than 1% of all breast cancer diagnoses worldwide. Most data on male breast cancer comes from small single-institution studies, and because of the paucity of data, the optimal treatment for male breast cancer is not known. This article summarizes a multidisciplinary international meeting on male breast cancer, sponsored by the National Institutes of Health Office of Rare Diseases and the National Cancer Institute Divisions of Cancer Epidemiology and Genetics and Cancer Treatment and Diagnosis. The meeting included representatives from the fields of epidemiology, genetics, pathology and molecular biology, health services research, and clinical oncology and the advocacy community, with a comprehensive review of the data. Presentations focused on highlighting differences and similarities between breast cancer in males and females. To enhance our understanding of male breast cancer, international consortia are necessary. Therefore, the Breast International Group and North American Breast Cancer Group have joined efforts to develop an International Male Breast Cancer Program and to pool epidemiologic data, clinical information, and tumor specimens. This international collaboration will also facilitate the future planning of clinical trials that can address essential questions in the treatment of male breast cancer. PMID- 20308663 TI - Phase II trial of bevacizumab, thalidomide, docetaxel, and prednisone in patients with metastatic castration-resistant prostate cancer. AB - PURPOSE We previously demonstrated that thalidomide appears to add to the activity of docetaxel in metastatic castration-resistant prostate cancer (CRPC). Phase II studies combining docetaxel with bevacizumab have had substantial antitumor activity. We hypothesized that the combination of docetaxel plus these antiangiogenic drugs with different targets would have substantial clinical activity. To explore safety and efficacy, this was tested in mice and in human patients. PATIENTS AND METHODS Preclinical efficacy of the combination therapy was evaluated in PC3 xenograft mice. Sixty patients with progressive metastatic CRPC received intravenous docetaxel and bevacizumab plus oral thalidomide and prednisone. The primary end point was a prostate-specific antigen (PSA) decline of > or = 50%. Secondary end points included time to progression, overall survival, and safety. Results In the mouse model, combination therapy of docetaxel, bevacizumab, and thalidomide inhibited tumor growth most effectively. In the clinical trial, 90% of patients receiving the combination therapy had PSA declines of > or = 50%, and 88% achieved a PSA decline of > or = 30% within the first 3 months of treatment. The median time to progression was 18.3 months, and the median overall survival was 28.2 months in this group with a Halabi-predicted survival of 14 months. While toxicities were manageable, all patients developed grade 3/4 neutropenia. CONCLUSION The addition of bevacizumab and thalidomide to docetaxel is a highly active combination with manageable toxicities. The estimated median survival is encouraging, given the generally poor prognosis of this patient population. These results suggest that definitive clinical trials combining antiangiogenic agent combinations with docetaxel are warranted to improve treatment outcomes for patients with metastatic CRPC. PMID- 20308664 TI - Lymph node staging by positron emission tomography in cervical cancer: relationship to prognosis. AB - PURPOSE A previous retrospective study demonstrated that positron emission tomography with [(18)F]fluorodeoxyglucose (FDG-PET) was more sensitive than computed tomography for lymph node staging in patients with cervical cancer; the findings on FDG-PET were strongly associated with progression-free survival. Therefore, a prospective cohort study was initiated to evaluate FDG-PET lymph node staging in a larger patient population. PATIENTS AND METHODS The study was conducted between July 2000 and March 2009. All 560 patients with cervical cancer underwent pretreatment FDG-PET lymph node staging. Treatment included surgery alone, surgery and postoperative radiation therapy, and definitive radiation or combination radiation and chemotherapy. PET findings were correlated with the risk of disease progression and with survival. Results Overall, 47% of patients had lymph node involvement by FDG-PET at diagnosis. The frequency of lymph node metastasis increased with clinical stage and was similar to that in historical surgical series. Within a stage, patients with PET-positive lymph nodes had significantly worse disease-specific survival than those with PET-negative lymph nodes (P < .001). Disease-specific survival was stratified into distinct groups based on the most distant level of PET-detected nodal disease (none, pelvic, para aortic, or supraclavicular; P < .001). The hazard ratios for disease recurrence increased incrementally based on the most distant level of nodal disease: pelvic 2.40 (95% CI, 1.63 to 3.52), para-aortic 5.88 (95% CI, 3.80 to 9.09), and supraclavicular 30.27 (95% CI 16.56 to 55.34). CONCLUSION Nodal involvement detected by FDG-PET in cervical cancer relates to clinical stage, is comparable to historical data, and stratifies patient recurrence and survival outcomes. PMID- 20308665 TI - Safety, pharmacokinetics, and preliminary clinical activity of inotuzumab ozogamicin, a novel immunoconjugate for the treatment of B-cell non-Hodgkin's lymphoma: results of a phase I study. AB - PURPOSE Inotuzumab ozogamicin (CMC-544) is an antibody-targeted chemotherapy agent composed of a humanized anti-CD22 antibody conjugated to calicheamicin, a potent cytotoxic agent. This was a phase I study to determine the maximum tolerated dose (MTD), safety, and preliminary efficacy of inotuzumab ozogamicin in an expanded MTD cohort of patients with relapsed or refractory CD22(+) B-cell non-Hodgkin's lymphoma (NHL). PATIENTS AND METHODS Inotuzumab ozogamicin was administered intravenously as a single agent once every 3 or 4 weeks at doses ranging from 0.4 to 2.4 mg/m(2). Outcomes included MTD, safety, pharmacokinetics, response, progression-free survival (PFS), and overall survival. Results Seventy nine patients were enrolled. The MTD was determined to be 1.8 mg/m(2). Common adverse events at the MTD were thrombocytopenia (90%), asthenia (67%), and nausea and neutropenia (51% each). The objective response rate at the end of treatment was 39% for the 79 enrolled patients, 68% for all patients with follicular NHL treated at the MTD, and 15% for all patients with diffuse large B-cell lymphoma treated at the MTD. Median PFS was 317 days (approximately 10.4 months) and 49 days for patients with follicular NHL and diffuse large B-cell lymphoma, respectively. CONCLUSION Inotuzumab ozogamicin has demonstrated efficacy against CD22(+) B-cell NHL, with reversible thrombocytopenia as the main toxicity. PMID- 20308666 TI - Do radiation-associated soft tissue sarcomas have the same prognosis as sporadic soft tissue sarcomas? AB - PURPOSE To determine the prognostic significance of histologic type in radiation associated soft tissue sarcomas (RASs) and determine whether RASs are associated with an inferior prognosis compared with sporadic soft tissue sarcomas (STSs). PATIENTS AND METHODS One hundred thirty primary RASs were identified from 7,649 STS patients from 1982 to 2007. Multivariate analysis of clinicopathologic factors for disease-specific survival (DSS) was performed for RASs, and a multivariate analysis of radiation exposure was also performed for RASs and sporadic sarcomas. A matched-cohort analysis was performed for radiation associated and sporadic malignant fibrous histiocytoma (MFH). Results Most RASs were high grade (83%), deep (87%), and truncal (61.5%). The median interval between radiation therapy and RAS development was 10 years (range, 1.3 to 74 years), which varied significantly by histologic type (P = .003). The 5-year DSS was 58%, and independent predictors were size > 5 cm, margin positivity, and histologic type. Multivariate analysis of histologic types of primary, high-grade radiation-associated and sporadic STSs showed that RAS was associated with a worse DSS (hazard ratio, 1.7; range, 1.1 to 2.4; P = .007). For pleomorphic MFH the most common RAS type-the 5-year DSS was 44% versus 66% in a matched cohort of sporadic MFH patients (P = .07). DSS was significantly worse in primary RAS malignant peripheral nerve sheath tumors (MPNSTs) compared with unmatched sporadic MPNSTs (P = .001). CONCLUSION Histologic type, margin status, and tumor size are the most important independent predictors of DSS in patients with RASs. DSS in patients with primary RAS is significantly worse compared with sporadic STS independent of sarcoma histologic type. PMID- 20308667 TI - Nomogram to predict subsequent brain metastasis in patients with metastatic breast cancer. AB - PURPOSE Brain metastasis is usually a fatal event in patients with stage IV breast cancer. We hypothesized that its occurrence can be predicted if a clinical nomogram can be developed, thus allowing for selection of enriched patient populations for prevention trials. PATIENTS AND METHODS Electronic medical records of patients with metastatic breast cancer were retrospectively reviewed for the period between January 2000 and February 2007 under a study approved by the institutional review board. A multivariate logistic regression analysis of selected prognostic features was done. A nomogram to predict brain metastasis was constructed and validated in a cohort of 128 patients with brain metastasis treated at the Cross Cancer Institute (Edmonton, Alberta, Canada). Results Of 2,136 patients with breast cancer, 362 developed subsequent brain metastasis. Age, grade, negative status of estrogen receptor and human epidermal growth factor receptor 2, number of metastatic sites (one v > one), and short disease free survival were significantly and independently associated with subsequent brain metastasis. The nomogram showed an area under the receiver operating characteristic curve (AUC) of 0.68 (95% CI, 0.66 to 0.69) in the training set. The validation set showed a good discrimination with an AUC of 0.74 (95% CI, 0.70 to 0.79). The nomogram was well calibrated, with no significant difference between the predicted and the observed probabilities. CONCLUSION We have developed a robust tool that is able to predict subsequent brain metastasis in patients with breast cancer with nonbrain metastatic disease. Selection of an enriched patient population at high risk for brain metastasis will facilitate the design of trials aiming at its prevention. PMID- 20308668 TI - Lymphoma recurrence 5 years or later following diffuse large B-cell lymphoma: clinical characteristics and outcome. AB - PURPOSE Patients with diffuse large B-cell lymphoma (DLBCL) usually relapse early following diagnosis but some relapses happen at 5 years or later. Few data exist regarding clinical characteristics and outcome of these patients. PATIENTS AND METHODS We performed a retrospective analysis of all patients from two centers in Lyon, France, between 1985 and 2003 who had a biopsy-proven relapse 5 years or later following diagnosis of DLBCL. All available biopsies were reviewed and immunohistochemistry was completed. Results Among 1,492 patients with DLBCL, 54 were eligible. At diagnosis, 63% of patients had stage I-II, 82% had low/low intermediate International Prognostic Index (IPI) score, 65% had extranodal involvement, 24% had an indolent component associated with DLBCL, 57% had germinal center phenotype, and 43% had non-germinal center phenotype. Median time from diagnosis to relapse was 7.4 years (range, 5 to 20.5 years). At time of relapse, 83% had DLBCL histology, and 17% had indolent histology. Having an indolent component at diagnosis was associated with indolent histology at relapse (P = .028). Five-year event free-survival (EFS) was 17% for patients with DLBCL relapse and 61% for patients with indolent relapse (P = .027). Five-year overall survival was 27% for patients with DLBCL and 75% for patients with indolent relapse (P = .029). For DLBCL relapse, 3-year EFS was 56% versus 18% with autologous stem-cell transplantation or not, respectively (P = .0661). CONCLUSION Patients with DLBCL who had a late relapse usually had localized stage, favorable IPI score, and extranodal involvement at diagnosis. The outcome of patients with DLBCL at time of relapse remains poor, and aggressive treatment such as autologous stem-cell transplantation should be pursued whenever possible. Biopsy at relapse is essential because some patients relapse with indolent histology. PMID- 20308669 TI - Current treatment protocols have eliminated the prognostic advantage of type 1 fusions in Ewing sarcoma: a report from the Children's Oncology Group. AB - PURPOSE Ewing sarcoma family tumors (ESFTs) exhibit chromosomal translocations that lead to the creation of chimeric fusion oncogenes. Combinatorial diversity among chromosomal breakpoints produces varying fusions. The type 1 EWS-FLI1 transcript is created as a result of fusion between exons 7 of EWS and 6 of FLI1, and retrospective studies have reported that type 1 tumors are associated with an improved outcome. We have re-examined this association in a prospective cohort of patients with ESFT treated according to current Children's Oncology Group (COG) treatment protocols. METHODS Frozen tumor tissue was prospectively obtained from patients diagnosed with ESFT, and reverse transcriptase polymerase chain reaction (RT-PCR) was used to determine translocation status. Analysis was confined to patients with localized tumors who were diagnosed after 1994 and treated according to COG protocols. Translocation status was correlated with disease characteristics, event-free survival (EFS), and overall survival (OS). Results RT PCR identified chimeric fusion oncogenes in 119 of 132 ESFTs. Eighty-nine percent of identified transcripts were EWS-FLI1, and of these, 58.8% were type 1. Five year EFS and OS rates for patients with type 1 and non-type 1 fusions diagnosed between 2001 and 2005 were equivalent (type 1: EFS, 63% +/- 7%; OS, 83% +/- 6%; non-type 1: EFS, 71% +/- 9%; OS, 79% +/- 8%). CONCLUSION Current intensive treatment protocols for localized ESFT have erased the clinical disadvantage that was formerly observed in patients with non-type 1 EWS-FLI1 fusions. PMID- 20308670 TI - Neoadjuvant treatment with trastuzumab in HER2-positive breast cancer: results from the GeparQuattro study. AB - PURPOSE Trastuzumab, a humanized antibody against the human epidermal growth factor receptor type 2 (HER2), has shown high efficacy in breast cancer. We prospectively investigated its efficacy given simultaneously with anthracycline taxane-based neoadjuvant chemotherapy. PATIENTS AND METHODS Patients with operable or locally advanced, HER2-positive tumors were treated preoperatively with four cycles of epirubicin/cyclophosphamide followed by four cycles of docetaxel with or without capecitabine (EC-T[X]) and trastuzumab 6 mg/kg (with a loading dose of 8 mg/kg) every 3 weeks during all chemotherapy cycles. Patients with HER2-negative tumors treated in the same study with the same chemotherapy but without trastuzumab were used as a reference group. Results Of 1,509 participants, 445 had HER2-positive tumors treated with trastuzumab and chemotherapy. Pathologic complete response (pCR; defined as no invasive or in situ residual tumors in the breast) rate was 31.7%, which was 16% higher than that in the reference group (15.7%). HER2-positive patients without response to the first four cycles of EC showed an unexpectedly high pCR rate of 16.6% (3.3% in the reference group). Breast conservation rate was 63.1% and comparable to that of the reference group (64.7%). EC-T(X) plus trastuzumab was associated with more febrile neutropenia and conjunctivitis, but with a comparable short-term cardiac toxicity profile as the reference group. CONCLUSION This trial confirms that combining trastuzumab with anthracycline-taxane-based neoadjuvant chemotherapy results in a high pCR rate without clinically relevant early toxicity. Combination of chemotherapy with trastuzumab should be considered when neoadjuvant treatment is given to patients with HER2-positive breast cancer. PMID- 20308671 TI - Capecitabine in addition to anthracycline- and taxane-based neoadjuvant treatment in patients with primary breast cancer: phase III GeparQuattro study. AB - PURPOSE Capecitabine can be integrated either concomitantly or sequentially to anthracycline-plus-taxane-based regimens. PATIENTS AND METHODS Patients with large operable or locally advanced tumors, with hormone receptor-negative tumors, or with receptor-positive tumors but also clinically node-positive disease were recruited to receive preoperatively four cycles of epirubicin plus cyclophosphamide (EC; epirubicin 90 mg/m(2) and cyclophosphamide 600 mg/m(2)). Patients were then randomly assigned to four cycles of docetaxel (100 mg/m(2)), four cycles of docetaxel + capecitabine (TX; docetaxel 75 mg/m(2) plus capecitabine 1,800 mg/m(2)), or four cycles of docetaxel (75 mg/m(2)) followed by four cycles of capecitabine (1,800 mg/m(2); T-X). Patients with human epidermal growth factor receptor 2 (HER-2) -positive tumors received trastuzumab concomitantly with all cycles. Primary objectives were to assess the effect of docetaxel by comparing EC plus docetaxel versus EC plus TX and to assess the effect of duration by comparing EC plus TX versus EC plus T-X on pathologic complete response (pCR, without invasive/noninvasive breast tumor, regardless of nodal status) at surgery, irrespective of trastuzumab treatment. Results Of 1,509 patients starting EC, 1,421 were randomly assigned to docetaxel (n = 471), TX (n = 471), or T-X (n = 479). At surgery, pCR rates were 22.3%, 19.5%, and 22.3%, respectively; the difference for docetaxel (EC plus docetaxel v EC plus TX) was 2.8% (95% CI, -2.4% to 8.0%; P = .298).The difference for duration was -2.8% (95% CI, -8.0% to 2.4%; P = .298). Breast conservation rates were 70.1%, 68.4%, and 65.3%, respectively (P = .781 for docetaxel; P = .270 for duration). Concomitant but not sequential treatment with docetaxel was associated with more diarrhea; nail changes, and hand-foot-syndrome, but it was associated with less edema. CONCLUSION Adding capecitabine to or prolonging duration of neoadjuvant EC plus docetaxel does not result in higher efficacy at surgery. PMID- 20308672 TI - Major tumor shrinking and persistent molecular remissions after consolidation with bortezomib, thalidomide, and dexamethasone in patients with autografted myeloma. AB - PURPOSE We investigated the effect on minimal residual disease, by qualitative and real-time quantitative polymerase chain reaction (RQ-PCR), of a consolidation regimen that included bortezomib, thalidomide, and dexamethasone (VTD) in patients with multiple myeloma (MM) responding to autologous stem-cell transplantation (auto-SCT). PATIENTS AND METHODS Patients achieving at least very good partial response who had an available molecular marker based on the immunoglobulin heavy-chain rearrangement received four courses of treatment every month: four infusions per month of bortezomib at 1.6 mg/m(2), thalidomide at 200 mg/d, and dexamethasone at 20 mg/d on days 1 to 4, 8 to 11, and 15 to 18. Patients were studied with tumor-clone-specific primers by qualitative nested PCR and RQ-PCR. Results Of 39 patients enrolled, 31 received the four VTD courses. Immunofixation complete responses increased from 15% after auto-SCT to 49% after VTD. Molecular remissions (MRs) were 3% after auto-SCT and 18% after VTD. Median time to maximum response was 3.5 months. So far, no patient in MR has relapsed (median follow-up, 42 months). VTD consolidation induced an additional depletion of 4.14 natural logarithms of tumor burden by RQ-PCR. Patients with a tumor load less than the median value after VTD had outcomes better than those who had tumor loads above the median value after VTD (at median follow-up: progression-free survival, 100% v 57%; P < .001). CONCLUSION To the best of our knowledge, this study is the first to document the occurrence of persistent MRs in a proportion of MM patients treated without allogeneic transplantation. Moreover, the major reduction in tumor load recorded by RQ-PCR after VTD suggests that unprecedented levels of tumor cell reduction can be achieved in MM thanks to the new nonchemotherapeutic drugs. PMID- 20308673 TI - Impact of EWS-ETS fusion type on disease progression in Ewing's sarcoma/peripheral primitive neuroectodermal tumor: prospective results from the cooperative Euro-E.W.I.N.G. 99 trial. AB - PURPOSE EWS-ETS fusion genes are the driving force in Ewing's sarcoma pathogenesis. Because of the variable breakpoint locations in the involved genes, there is heterogeneity in fusion RNA and protein architecture. Since previous retrospective studies suggested prognostic differences among patients expressing different EWS-FLI1 fusion types, the impact of fusion RNA architecture on disease progression and relapse was studied prospectively within the Euro-E.W.I.N.G. 99 clinical trial. PATIENTS AND METHODS Among 1,957 patients who registered before January 1, 2007, 703 primary tumors were accessible for the molecular biology study. Fusion type was assessed by polymerase chain reaction on frozen (n = 578) or paraffin-embedded materials (n = 125). The primary end point was the time to disease progression or relapse. Results After exclusion of noninformative patients, 565 patients were entered into the prognostic factor analysis comparing type 1 (n = 296), type 2 (n = 133), nontype 1/nontype 2 EWS-FLI1 (n = 91) and EWS ERG fusions (n = 45). Median follow-up time was 4.5 years. The distribution of sex, age, tumor volume, tumor site, disease extension, or histologic response did not differ between the four fusion type groups. We did not observe any significant prognostic value of the fusion type on the risk of progression or relapse. The only slight difference was that the risk of progression or relapse associated with nontype 1/nontype 2 EWS-FLI1 fusions was 1.38 (95% CI, 0.96 to 2.0) times higher than risk associated with other fusion types, but it was not significant (P = .10). CONCLUSION In contrast to retrospective studies, the prospective evaluation did not confirm a prognostic benefit for type 1 EWS-FLI1 fusions. PMID- 20308674 TI - Teaching neuroimages: T2 hypointense thalami in infantile GM1 gangliosidosis. PMID- 20308675 TI - Teaching neuroimages: confirmation of prenatal periventricular venous infarction with susceptibility-weighted MRI. PMID- 20308677 TI - Mild cognitive impairment and on to dementia: down the slippery slope but faster. PMID- 20308678 TI - CSF markers in amyotrophic lateral sclerosis: has the time come? PMID- 20308679 TI - Cognitive decline in incident Alzheimer disease in a community population. AB - OBJECTIVE: To measure the cognitive consequences of incident Alzheimer disease (AD) in older African American and white subjects. METHODS: Data are from the Chicago Health and Aging Project, a longitudinal cohort study of older white and black persons residing in a geographically defined community. At 3-year intervals, the entire study population completed 4 brief cognitive tests, from which a previously established composite measure of global cognition was derived, and a subset underwent detailed clinical evaluation that supported clinical classification of mild cognitive impairment, dementia, and AD. We used mixed effects models to examine change in cognitive function following the diagnostic evaluation. RESULTS: On clinical evaluation, 614 persons were found to have no cognitive impairment, 395 had mild cognitive impairment, and 149 had AD (88.5% mild); 10 persons with other dementias were excluded from analyses. During up to 11 years of observation following the clinical evaluation (mean = 5.5, SD = 2.5), the composite measure of global cognition declined a mean of 0.042 unit per year (SE = 0.008, p < 0.001) in those with no cognitive impairment. In comparison to the no cognitive impairment group, the annual rate of decline was increased more than twofold in mild cognitive impairment (estimate = 0.086, SE = 0.011, p < 0.001) and more than fourfold in AD (estimate = 0.173, SE = 0.020, p < 0.001). Results did not reliably vary by race, sex, or age. CONCLUSIONS: Alzheimer disease has a devastating impact on cognition, even in its prodromal stages, with comparable effects in African American and white persons. PMID- 20308680 TI - Does hypothermia influence the predictive value of bilateral absent N20 after cardiac arrest? AB - BACKGROUND: Bilateral absent N20 responses of median nerve somatosensory evoked potentials (SEPs) reliably predict poor prognosis after cardiac arrest. However, the studies supporting this fact were carried out before hypothermia was established as standard treatment. Recent evidence suggests that hypothermia treatment affects the predictive value of clinical findings in cardiac arrest patients, raising the question whether the predictive value of N20 responses has changed as well. METHODS: We retrospectively studied 185 consecutive patients treated with hypothermia after cardiac arrest. SEP recordings were available for 112 patients. SEPs were classified as bilateral absent N20, pathologic N20, or normal. Baseline and follow-up information were obtained from our database. RESULTS: We identified 36 patients with bilateral absent N20, 35 (97%) of whom had poor outcome. One patient had prolonged high amplitude peripheral SEP, but bilaterally absent N20 3 days after cardiac arrest and regained consciousness with normal cognitive functions and reproducible N20 responses. One further patient had minimally detectable N20 at day 3 and recovered consciousness and normal N20 responses on follow-up. CONCLUSIONS: Our data indicate that recovery of consciousness and cognitive functions is possible in spite of absent or minimally present N20 responses more than 24 hours after cardiac arrest in a very small proportion of patients. N20 responses may recover beyond this time window. The predictive value of bilateral absent N20 responses needs to be reevaluated in larger prospective studies. Until these studies are available, decisions to stop therapy in cardiac arrest survivors should not be based on N20 responses alone. PMID- 20308681 TI - Hyperfamiliarity for faces. AB - OBJECTIVE: To report 4 cases of hyperfamiliarity for faces (HFF) and review 5 previously reported cases. METHODS: We identified cases of HFF from PubMed search and references in prior reports. RESULTS: Three of our 4 cases had pathologic findings that were most extensive in the left temporal lobe. HFF occurred after a tonic-clonic seizure (cases 1 and 3), during simple partial seizures (case 2), and in the setting of an increase in simple partial seizure frequency but not during seizures (case 4). All 9 cases were adults with 1 or more seizures; symptoms first occurred after seizures in 5 cases and during seizures in 1 case. Ictal symptoms lasted from seconds to minutes and from 2 days to more than 7 years in the other 6 cases. The duration of HFF was not associated with the presence or extent of a structural lesion. While in several cases HFF appears to result from a postictal Todd paralysis, the mechanism underlying persistent cases is uncertain. CONCLUSIONS: This modality (visual)-specific and stimulus (face) specific syndrome is associated with diverse structural, functional imaging, and neurophysiologic findings. Lesions are more often left-sided and involve the temporal lobe. Epilepsy and seizures were present in all 9 cases, suggesting a pathophysiologic relationship, which likely varies among cases. Although only reported in 9 patients, HFF is probably much more common than it is diagnosed. PMID- 20308682 TI - CSF glial markers correlate with survival in amyotrophic lateral sclerosis. AB - BACKGROUND: In neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS), CSF biomarkers are increasingly studied to evaluate their relevance for differential diagnosis, disease progression, and understanding of pathophysiologic processes. OBJECTIVE: To identify a biomarker profile of neuronal and glial CSF proteins to discriminate ALS from other motor neuron diseases (MND) and to assess whether baseline levels of CSF measures in ALS are associated with the course of the disease. METHODS: A total of 122 consecutive subjects with MND were included in this cross-sectional study (ALS, n = 75; lower motor neuron syndrome, n = 39; upper motor neuron diseases, n = 8). Clinical follow-up included 76 patients. We determined baseline levels of protein tau and astroglial S100beta in CSF and microglial sCD14 in CSF and serum in relation to diagnosis, duration of disease, and survival. RESULTS: CSF tau was significantly elevated in ALS and upper motor neuron diseases as compared to lower motor neuron diseases and controls. CSF S100beta levels were significantly lower in lower motor neuron diseases as compared to other MND. CSF concentrations of S100beta and sCD14 correlated with the survival time in patients with ALS. CONCLUSIONS: In motor neuron diseases, CSF tau elevation indicates the degeneration of upper motor neurons, while S100 beta and sCD14 may indicate the activation of CNS glial cells. Because S100beta and sCD14 concentrations correlate with survival in amyotrophic lateral sclerosis (ALS), we suppose that the combination of both markers may be useful to obtain prognostic information in patients with ALS. PMID- 20308683 TI - Diffusion tensor MRI changes in cerebellar structures of patients with familial essential tremor. AB - OBJECTIVE: The aim of our study was to investigate the microstructural integrity of brain regions functionally involved in the tremor loop in patients with familial essential tremor (FET), using diffusion tensor imaging (DTI). METHODS: Twenty-five patients with FET, 15 patients with Parkinson disease (PD), and 15 healthy subjects were studied. DTI was performed to measure fractional anisotropy (FA) and mean diffusivity (MD) in various regions of interest: red nucleus, dentate nucleus (DN), cerebellar white matter, middle (MCP) and superior cerebellar peduncle (SCP), and ventrolateral thalamus. RESULTS: In patients with FET, FA values in the DN (median 0.19, range 0.13-0.23) were reduced (p < 0.001) compared with patients with PD (median 0.37, range 0.32-0.58) and healthy controls (median 0.36, range 0.33-0.40). In patients with FET, FA was also reduced (p = 0.003) and MD values increased (p < 0.001) in the SCP compared with patients with PD and healthy controls. Among patients with FET, those with longer disease duration showed FA values in the DN lower than those with shorter disease duration (p = 0.018). Patients with FET could be completely distinguished from both patient with PD and healthy controls using FA values of the DN alone. CONCLUSION: Neuroimaging evidence of microstructural changes consistent with neurodegeneration was found in the dentate nucleus (DN) and SCP of patients with familial essential tremor. This suggests that neurodegenerative pathology of cerebellar structures may play a role in essential tremor. Further studies are needed to assess the role of fractional anisotropy and mean diffusivity changes in DN and SCP in the differential diagnosis of essential tremor and Parkinson disease, which may present similar clinical signs at the onset of disease. PMID- 20308685 TI - New-onset refractory status epilepticus with restricted DWI and neuronophagia in the pulvinar. PMID- 20308684 TI - Anti-inflammatory drugs and risk of Parkinson disease: a meta-analysis. AB - BACKGROUND/OBJECTIVE: Anti-inflammatory drugs may prevent Parkinson disease (PD) by inhibiting a putative underlying neuroinflammatory process. We tested the hypothesis that anti-inflammatory drugs reduce PD incidence and that there are differential effects by type of anti-inflammatory, duration of use, or intensity of use. METHODS: MEDLINE and EMBASE were searched for studies that reported risk of PD associated with anti-inflammatory medications. Random-effects meta-analyses were used to pool results across studies for each type of anti-inflammatory drug. Stratified meta-analyses were used to assess duration- and intensity-response. RESULTS: Seven studies were identified that met the inclusion criteria, all of which reported associations between nonaspirin nonsteroidal anti-inflammatory drugs (NSAIDs) and PD, 6 of which reported on aspirin, and 2 of which reported on acetaminophen. Overall, a 15% reduction in PD incidence was observed among users of nonaspirin NSAIDS (relative risk [RR] 0.85, 95% confidence interval [CI] 0.77 0.94), with a similar effect observed for ibuprofen use. The protective effect of nonaspirin NSAIDs was more pronounced among regular users (RR 0.71, 95% CI 0.58 0.89) and long-term users (RR 0.79, 95% CI 0.59-1.07). No protective effect was observed for aspirin (RR 1.08, 95% CI 0.92-1.27) or acetaminophen (RR 1.06, 95% CI 0.87-1.30). Sensitivity analyses found results to be robust. CONCLUSIONS: There may be a protective effect of nonaspirin nonsteroidal anti-inflammatory drug use on risk of Parkinson disease (PD) consistent with a possible neuroinflammatory pathway in PD pathogenesis. PMID- 20308686 TI - Microstructural white matter changes in metabolic syndrome: a diffusion tensor imaging study. PMID- 20308687 TI - How did stroke become of interest to neurologists? A slow 19th century saga. PMID- 20308688 TI - Randomized, controlled trial of telcagepant for the acute treatment of migraine. PMID- 20308689 TI - Pharmacokinetics and safety of a single intravenous dose of the antibiotic tigecycline in patients with cirrhosis. AB - Tigecycline belongs to a new class of tetracyclines, the glycylcyclines, less than 20% of which is metabolized in the liver. Twenty-five patients with cirrhosis with varying degrees of functional hepatic reserve (Child-Pugh A, n = 10; B, n = 10; C, n = 5) and 23 healthy adults, matched by age, sex, weight, and smoking habits, received 100 mg of tigecycline infused intravenously over 60 minutes. Serum and urine samples were collected up to 120 hours after dosing. Pharmacokinetic data were derived using noncompartmental methods. The most common treatment-emergent adverse events in healthy volunteers were nausea (56.5%), vomiting (21.7%), and headache (21.7%) and in the patients with cirrhosis, albuminuria (12%). Mean (+/- 1 SD) tigecycline clearance values were 29.8 +/- 11.3 L/h in healthy subjects and 31.2 +/- 13.9 L/h (Child-Pugh A), 22.1 +/- 9.3 L/h (Child-Pugh B), and 13.5 +/- 2.7 L/h (Child-Pugh C) in the patients. A single intravenous dose of tigecycline 100 mg was safe and well-tolerated in patients with cirrhosis with varying degrees of hepatic functional reserve. No adjustment of tigecycline maintenance dosage is warranted in patients with compensated or moderately decompensated cirrhosis; doses should be reduced by 50%, to 25 mg, every 12 hours in patients with severely decompensated disease. PMID- 20308690 TI - Capecitabine-induced, rapid decrease of renal function due to drug dispensing error in a hospital pharmacy. PMID- 20308692 TI - Reliability, usefulness, and validity of a repeated sprint and jump ability test. AB - PURPOSE: Two studies involving 122 handball players were conducted to assess the reliability, usefulness, and validity of a repeated shuttle-sprint and jump ability (RSSJA) test. The test consisted of 6x(2x12.5-m) sprints departing on 25 s, with a countermovement jump performed during recovery between sprints. METHODS: For the reliability and usefulness study, 14 well-trained male handball players performed the RSSJA test 7 d apart. Reliability of the test variables was assessed by the typical error of measurement, expressed as a coefficient of variation (CV). The minimal changes likely to be "real" in sprint time and jump power were also calculated. For the validity study, players of seven teams (national to international levels, women and men) performed the RSSJA test. RESULTS: CV values for best and mean sprint time were 1.0% (90% CL, 0.7 to 1.6) and 1.0% (90% CL, 0.7 to 1.4). CV values for best and mean jump peak power were 1.7% (90% CL, 1.2 to 2.7) and 1.5% (90% CL, 1.1 to 2.5). The percent sprint and jump decrements were less reliable, with CVs of 22.3% (90% CL, 15.7 to 38.3) and 34.8% (90% CL, 24.2 to 61.8). Minimal changes likely to be "real" for mean sprint time and jumping peak power were -2.6% and 4.8%. Qualitative analysis revealed that the majority of between-team differences were rated as "almost certain" (ie, 100% probability that the true differences were meaningful) for mean sprint and jump performances. CONCLUSION: The RSSJA test is reliable and valid to assess repeated explosive effort sequences in team sports such as handball. Test results are likely to be representative of gender and competition level; thus the test could be used to discriminate across playing standards and monitor fitness levels. PMID- 20308691 TI - Identification of a hormone-regulated dynamic nuclear actin network associated with estrogen receptor alpha in human breast cancer cell nuclei. AB - Estrogen receptor alpha (ERalpha) is a modular protein of the steroid/nuclear receptor family of transcriptional regulators that upon binding to the hormone undergoes structural changes, resulting in its nuclear translocation and docking to specific chromatin sites. In the nucleus, ERalpha assembles in multiprotein complexes that act as final effectors of estrogen signaling to the genome through chromatin remodeling and epigenetic modifications, leading to dynamic and coordinated regulation of hormone-responsive genes. Identification of the molecular partners of ERalpha and understanding their combinatory interactions within functional complexes is a prerequisite to define the molecular basis of estrogen control of cell functions. To this end, affinity purification was applied to map and characterize the ERalpha interactome in hormone-responsive human breast cancer cell nuclei. MCF-7 cell clones expressing human ERalpha fused to a tandem affinity purification tag were generated and used to purify native nuclear ER-containing complexes by IgG-Sepharose affinity chromatography and glycerol gradient centrifugation. Purified complexes were analyzed by two dimensional DIGE and mass spectrometry, leading to the identification of a ligand dependent multiprotein complex comprising beta-actin, myosins, and several proteins involved in actin filament organization and dynamics and/or known to participate in actin-mediated regulation of gene transcription, chromatin dynamics, and ribosome biogenesis. Time course analyses indicated that complexes containing ERalpha and actin are assembled in the nucleus early after receptor activation by ligands, and gene knockdown experiments showed that gelsolin and the nuclear isoform of myosin 1c are key determinants for assembly and/or stability of these complexes. Based on these results, we propose that the actin network plays a role in nuclear ERalpha actions in breast cancer cells, including coordinated regulation of target gene activity, spatial and functional reorganization of chromatin, and ribosome biogenesis. PMID- 20308693 TI - Caffeine does not augment markers of muscle damage or leukocytosis following resistance exercise. AB - PURPOSE: The purpose of this study was to evaluate the effects of caffeine ingestion before a resistance exercise session on markers of muscle damage (CK, LDH, ALT, AST) and leukocyte levels. METHODS: Fifteen soccer athletes completed two resistance exercise sessions that differed only in the ingestion of caffeine or a placebo preworkout. RESULTS: CK concentration increased significantly following the caffeine session (415.8+/-62.8 to 542.0+/-73.5) and the placebo session (411.5+/-43.3 to 545.8+/-59.9), with no significant differences between sessions. Similarly, LDH concentration increased significantly following the caffeine session (377.5+/-18.0 to 580.5+/-36.1) and the placebo session (384.8+/ 13.9 to 570.4+/-36.1), with no significant differences between sessions. Both sessions resulted in significant increases in the total leukocyte count (caffeine=6.24+/-2.08 to 8.84+/-3.41; placebo=6.36+/-2.34 to 8.77+/-3.20), neutrophils (caffeine=3.37+/-0.13 to 5.15+/-0.28; placebo=3.46+/-0.17 to 5.12+/ 0.24), lymphocytes (caffeine=2.19+/-0.091 to 2.78+/-0.10; placebo=2.17+/-0.100 to 2.75+/-0.11), and monocytes (caffeine=0.53+/-0.02 to 0.72+/-0.06; placebo=0.56+/ 0.03 to 0.69+/-0.04), with no significant differences between sessions. CONCLUSION: Ingestion of caffeine at 4.5 mg/kg(-1) did not augment markers of muscle damage or leukocyte levels above that which occurs through resistance exercise alone. PMID- 20308694 TI - Effects of acute multinutrient supplementation on rugby union game performance and recovery. AB - PURPOSE: To investigate the effects of an acute multinutrient supplement on game based running performance, peak power output, anaerobic by-products, hormonal profiles, markers of muscle damage, and perceived muscular soreness before, immediately after, and 24 h following competitive rugby union games. METHODS: Twelve male rugby union players ingested either a comprehensive multinutrient supplement (SUPP), [RE-ACTIVATE:01], or a placebo (PL) for 5 d. Participants then performed a competitive rugby union game (with global positioning system tracking), with associated blood draws and vertical jump assessments pre, immediately post and 24 h following competition. RESULTS: SUPP ingestion resulted in moderate to large effects for augmented 1st half very high intensity running (VHIR) mean speed (5.9+/-0.4 vs 4.8+/-2.3 mxmin(-1); d=0.93). Further, moderate increases in 2nd half VHIR distance (137+/-119 vs 83+/-89 m; d=0.73) and VHIR mean speed (5.9+/-0.6 vs 5.3+/-1.7 mxmin(-1); d=0.56) in SUPP condition were also apparent. Postgame aspartate aminotransferase (AST; 44.1+/-11.8 vs 37.0+/-3.2 UL; d=1.16) and creatine kinase (CK; 882+/-472 vs 645+/-123 UL; d=0.97) measures demonstrated increased values in the SUPP condition, while AST and CK values correlated with 2nd half VHIR distance (r=-0.71 and r=-0.76 respectively). Elevated C-reactive protein (CRP) was observed postgame in both conditions; however, it was significantly blunted with SUPP (P=.05). CONCLUSIONS: These findings suggest SUPP may assist in the maintenance of VHIR during rugby union games, possibly via the buffering qualities of SUPP ingredients. However, correlations between increased work completed at very high intensities and muscular degradation in SUPP conditions, may mask any anticatabolic properties of the supplement. PMID- 20308695 TI - Acute carbohydrate ingestion affects lactate response in highly trained swimmers. AB - PURPOSE: Effects of acute carbohydrate ingestion on blood lactate (BLa) response to graded exercise was examined in highly trained male and female swimmers. METHODS: Twenty-three swimmers performed the United States Swimming Lactate Protocol, a graded interval test (5x200 on 5 min), following ingestion of carbohydrate sports drink (CHO) and placebo (PLA). RESULTS: There was no difference in heart rate (P=.55), swim velocity (P=.95), or ratings of perceived exertion (P=.58) between beverages. There was a significant main effect for gender (P=.002) on BLa during all swim stages and recovery. In females, BLa was 27% to 50% higher for CHO during the first (P=.009) and second (P=.04) swim stages. Predicted BLa at selected swim velocity was higher (P=.048) for CHO versus PLA in females at 1.27 mxs(-1) and higher (P<.02) for men at 1.4 mxs(-1). Mean (+/-SD) BLa was significantly (P=.004) greater for CHO (2.7+/-1.2) compared with PLA (2.0+/-1.1 mmolxL(-1)) during the second test stage and when normalized relative to velocity (P=.004). Peak BLa after the final swim (9.6+/-3.1 vs. 9.0+/ 3.2 mmolxL(-1), P=.36) was not different between CHO and PLA. CONCLUSIONS: Acute CHO ingestion alters the BLa: swim velocity relationship during moderate intensity swims of an incremental swim test, particularly for females. Therefore, pretest beverage ingestion should be standardized during the administration of BLa testing to prevent potential erroneous interpretations regarding athlete's training status. PMID- 20308696 TI - Heart rate responses and fluid balance of competitive cross-country hang gliding pilots. AB - PURPOSE: To evaluate the physiological challenges of competitive cross-country hang gliding. METHODS: Seventeen experienced male pilots (age=41+/-9 y; mean+/ SD) were fitted with a monitor that recorded heart rate and altitude at 0.5 Hz throughout a competitive flight. Fluid losses were evaluated by comparing pilot pre- and postflight mass. RESULTS: The pilots' displacement was 88.4+/-43.7 km in 145.5+/-49.4 min. Mean flight altitude was 1902+/-427 m (range=1363-2601 m) with a maximum altitude of 2925+/-682 m (1870-3831 m). The mean in-flight heart rate of the pilots was 112+/-11 bpm (64+/-6% predicted HRmax). For all except one subject, heart rate was highest while launching (165+/-12 bpm, 93+/-7% predicted HRmax), followed by landing (154+/-13 bpm, 87+/-7% predicted HRmax). No statistically significant relationship was observed between heart rate during the launch and reported measures of state anxiety. Heart rate was inversely related (P<.01) to altitude for all pilots except one. Fluid loss during the flight was 1.32+/-0.70 L, which approximated 0.55 L/h, while mean in-flight fluid consumption was 0.39+/-0.44 L. Six pilots consumed no fluid during the flight. CONCLUSIONS: Even among experienced pilots, high heart rates are more a function of state anxiety than physical work demand. Fluid losses during flight are surprisingly moderate but pilots may still benefit from attending to fluid balance. PMID- 20308697 TI - The Bath University Rugby Shuttle Test (BURST): a pilot study. AB - PURPOSE: This study presents an exercise protocol utilizing movement patterns specific to rugby union forward and assesses the reproducibility of scores from this test. METHODS: After habituation, eight participants (mean+/-SD: age=21+/-3 y, height=180+/-4 cm, body mass=83.9+/-3.9 kg) performed the Bath University Rugby Shuttle Test (BURST) on two occasions, 1 wk apart. The protocol comprised 16x315-s cycles (4x21-min blocks) of 20-m shuttles of walking and cruising with 10-m jogs, with simulated scrummaging, rucking, or mauling exercises and standing rests. In the last minute of every 315-s cycle, a timed Performance Test was carried out, involving carrying a tackle bag and an agility sprint with a ball, followed by a 25-s recovery and a 15-m sprint. RESULTS: Participants traveled 7078 m, spending 79.8 and 20.2% of time in low- and high-intensity activity, respectively. The coefficients of variation (CV) between trials 1 and 2 for mean time on the Performance Test (17.78+/-0.71 vs 17.58+/-0.79 s) and 15-m sprint (2.69+/-0.15 vs 2.69+/-0.15 s) were 1.3 and 0.9%, respectively. There was a CV of 2.2% between trials 1 and 2 for mean heart rate (160+/-5 vs 158+/-5 beats x min( 1)) and 14.4% for blood lactate (4.41+/-1.22 vs 4.68+/-1.68 mmolxL(-1)). CONCLUSION: Results suggest that measures of rugby union-specific high-intensity exercise performed during the BURST were reproducible over two trials in habituated participants. PMID- 20308698 TI - The physical and physiological demands of basketball training and competition. AB - PURPOSE: To characterize the physical and physiological responses during different basketball practice drills and games. METHODS: Male basketball players (n=11; 19.1+/-2.1 y, 1.91+/-0.09 m, 87.9+/-15.1 kg; mean+/-SD) completed offensive and defensive practice drills, half court 5on5 scrimmage play, and competitive games. Heart rate, VO2, and triaxial accelerometer data (physical demand) were normalized for individual participation time. Data were log transformed and differences between drills and games standardized for interpretation of magnitudes and reported with the effect size (ES) statistic. RESULTS: There was no substantial difference in the physical or physiological variables between offensive and defensive drills; physical load (9.5%; 90% confidence limits+/-45); mean heart rate (-2.4%; +/-4.2); peak heart rate (-0.9%; +/-3.4); and VO2 (-5.7%; +/-9.1). Physical load was moderately greater in game play compared with a 5on5 scrimmage (85.2%; +/-40.5); with a higher mean heart rate (12.4%; +/-5.4). The oxygen demand for live play was substantially larger than 5on5 (30.6%; +/-15.6). CONCLUSIONS: Defensive and offensive drills during basketball practice have similar physiological responses and physical demand. Live play is substantially more demanding than a 5on5 scrimmage in both physical and physiological attributes. Accelerometers and predicted oxygen cost from heart rate monitoring systems are useful for differentiating the practice and competition demands of basketball. PMID- 20308699 TI - The effect of prior endurance training on nap sleep patterns. AB - PURPOSE: The use of daytime napping as a recovery tool following exercise is virtually unexplored. The objective of this study was to assess the quality of daytime nap sleep following endurance training in an athletic population, and to appraise the optimal circadian timing of the nap and the time interval between training and the nap. METHODS: Six physically trained male subjects (22.5+/-2.4 y) performed four separate standardized 90-min endurance training sessions followed by a 90-min daytime nap either 1 or 2 h after training (time interval), commencing at either 10:30 or 11:30 (circadian timing). During the nap, sleep was monitored using polysomnography. Subjective measurements of sleep quality, alertness and preparedness to train following a nap were recorded using a visual analog scale. RESULTS: The duration of slow wave sleep (SWS) was significantly greater during the 11:30 naps (13.7+/-9.0 min) compared with the 10:30 naps (6.9+/-8.8 min) (P=.049). There was no significant difference in SWS duration between a 1-h (10.6+/-10.2 min) or 2-h (10.0+/-9.0 min) time interval between training and the nap (P=.82). No other sleep variables differed significantly according to circadian timing or time interval. CONCLUSION: Recovery naps commenced later in the morning contain more SWS than earlier naps. The data imply that daytime naps have a potential role as a valuable recovery tool following endurance exercise, given the suggested energy restorative functions of SWS. PMID- 20308700 TI - Elite athletes: are the genes the champions? AB - Recent research has analyzed the genetic factors that influence world-class athletic status. Much of what we know comes from association studies, with the ACE I/D and ACTN3 R577X polymorphisms having been extensively studied. The association between the ACTN3 R577X variation and elite athlete status in power sports is strongly documented, yet whether the current body of knowledge on other variants can be extrapolated to athletic champion status remains to be determined. Athletic champion status is a complex polygenic trait in which numerous candidate genes, complex gene-gene interactions, and environment-gene interactions are involved. Besides the need for more studies and new approaches taking into account the complexity of the problem, we believe that factors beyond genetic endowment are likely to have a stronger influence in the attainment of athletic champion status. PMID- 20308701 TI - Talent development in adolescent team sports: a review. AB - Traditional talent development pathways for adolescents in team sports follow talent identification procedures based on subjective games ratings and isolated athletic assessment. Most talent development models are exclusive rather than inclusive in nature. Subsequently, talent identification may result in discontentment, premature stratification, or dropout from team sports. Understanding the multidimensional differences among the requirements of adolescent and elite adult athletes could provide more realistic goals for potential talented players. Coach education should include adolescent development, and rewards for team success at the adolescent level should reflect the needs of long-term player development. Effective talent development needs to incorporate physical and psychological maturity, the relative age effect, objective measures of game sense, and athletic prowess. The influences of media and culture on the individual, and the competing time demands between various competitions for player training time should be monitored and mediated where appropriate. Despite the complexity, talent development is a worthy investment in professional team sport. PMID- 20308702 TI - Reliability of an in-water repeated-sprint test for water polo. AB - Time-motion studies indicate the importance of repeated high-intensity activities during water polo match play. The purpose of this study was to assess the reliability of an in-water repeated-sprint test, which comprised 6x10-m all-out sprints, departing every 17 s. This protocol was chosen to replicate the regular intense periods of match play. PMID- 20308703 TI - Quicker, faster, better? PMID- 20308704 TI - Update in prolactinomas. AB - Prolactinomas are a frequent cause of gonadal dysfunction and infertility, especially in women. Dopamine agonists are first-line therapy and their efficacy in the treatment of prolactinomas is well established. Current challenges related to the management of prolactinomas remain in the recurrence of the disease after withdrawal of dopamine agonists, the potential of increased risk of cardiac valvulopathy, which is observed in patients treated with high-dose cabergoline for Parkinson's disease, the effects of pregnancy, and impaired quality of life associated with pituitary adenomas in general, and prolactinomas in particular. Although most prolactinomas are biochemically well controlled by pharmaceutical treatment, long-term follow-up is required. PMID- 20308705 TI - Role of vitamin D in cardiovascular disease. AB - There is increasing evidence for health benefits accomplished by activated vitamin D through interaction with the vitamin D receptor (VDR) that go beyond calcium and bone homeostasis and regulation of parathyroid hormone (PTH) secretion. Treatment with vitamin D receptor agonists (VDRAs) is associated with reduced mortality in (pre)dialysis patients. Interestingly, these relations are independent of PTH levels and calcium x phosphorus product. This suggests the presence of biological functions of vitamin D that are independent of its interaction with the parathyroid glands. Because chronic kidney disease leads to increased cardiovascular mortality, mechanisms in which VDRAs can influence cardiovascular disease are discussed. These mechanisms comprise the potential ameliorating effects of VDRAs on atherosclerosis, arterial media calcification, cardiac hypertrophy, the renin-angiotensin system and thrombosis. Moreover, treatment strategies with VDRAs are discussed together with several recent observational studies. Treatment advice consists of correction of 25(OH) vitamin D deficiency, low-dose calcitriol in patients with secondary hyperparathyroidism, and activated vitamin D analogues may be indicated when higher doses are needed to suppress PTH secretion. New insights into biological and clinical effects of VDRAs may broaden the patient group that may benefit from VDRA treatment to patients with creatinine clearances in the 30 to 60 ml/min range. PMID- 20308706 TI - Optimal nutrition and its potential effect on survival in critically ill patients. AB - Optimal nutrition serves to maintain normal organ function and to preserve body energy stores to guarantee survival during times of shortage of food. Especially total body protein content is an important determinant of survival. However, recommendations about nutrition refer mostly to total energy intake with either no emphasis on total protein content or protein intake only considered as a fixed percentage of caloric intake. This paper focuses on the role of total body protein mass or lean body mass (= mass of organs and muscle) (LBM) on survival of healthy humans and critically ill patients. Recommendations on the amount of protein per kg bodyweight are made based on the scarce evidence available in humans. PMID- 20308707 TI - Reduction of the door-to-needle time for administration of antibiotics in patients with a severe infection: a tailored intervention project. AB - BACKGROUND: Door-to-needle time (DNT), defined as the time between arrival at the emergency department (ED) and intravenous (iv) antibiotic administration is of crucial importance in the treatment of patients suffering from serious infections. The aim of this project was to reduce the DNT for patients with a serious infection as primary outcome parameter. METHODS: All adult patients arriving at the ED with a suspected infection for whom admission and iv antibiotics were indicated were included. RESULTS: Firstly, baseline DNT was measured and potential delaying factors were identified. Subsequently, five tailored interventions were implemented at regular intervals and their effects on the DNT were analysed. The interventions were: 1) additional resident attendance during peak hours, 2) immediate examination by residents prior to laboratory results, 3) chest X-ray at the ED instead of the external radiology department, 4) iv antibiotic administration at the ED instead of the ward and finally, 5) primary dipstick urine analysis at the ED. A total of 295 patients were included (53.9% men), median age was 59 years (IQR 46 to 73). Median baseline DNT was 183 min (IQR 122 to 296). Implementation of the first three interventions did not reduce the DNT ; however, after implementation of the fourth (administer all antibiotics at the ED) and finally all five interventions the DNT was reduced by 15.3% (p=0.040) to a final median DNT of 155 min (IQR 95 to 221). CONCLUSION: Identification of delaying factors and implementation of tailored interventions reduces the DNT . PMID- 20308708 TI - Sore throat after dumbbell exercises. PMID- 20308709 TI - A dysfunctional central venous line. PMID- 20308710 TI - An X-ray that helps to solve the puzzle. PMID- 20308711 TI - Hyperthyroidism caused by excessive consumption of sausages. AB - Hyperthyroidism results from excessive production of thyroid hormones. This is usually caused by Graves disease, but exogenous thyroid hormones can lead to similar symptoms. Recognition of the latter is difficult as excessive intake of thyroid hormone is not usually admitted nor recognised. To our knowledge, exogenous hyperthyroidism caused by thyroid-contaminated food has been described twice, but not in the Netherlands. A 77-year-old man presented at the Outpatient Department of Internal Medicine with lab values revealing hyperthyroidism. There were no abnormal findings at the physical examination. Antibodies against the thyroidstimulating hormone (TSH) receptor were not detectable. Thyroid scintigraphy with 123I showed an uptake of less than 1%. Silent thyroiditis was diagnosed and the natural course was awaited, but with no improvement in the thyroid values. The thyroglobulin was very low. Further anamnesis revealed an excessive daily consumption of sausages. Thyroid hormones were detectable in these sausages. After the patient stopped eating them, he became and remained euthyroid. The case stipulates the importance of a thorough anamnesis. PMID- 20308712 TI - Human recombinant insulin and amyloidosis: an unexpected association. AB - A 48-year-old patient with diabetes mellitus was treated with human (recombinant) insulin. He developed cutaneous amyloidosis twice at different locations where subcutaneous insulin had been injected. There were no signs of systemic amyloidosis. Additional pathological-anatomical investigations demonstrated insulin in one (the most recent) amyloid tumour. A limited number of similar cases have been reported in the literature, although mostly associated with porcine insulin. Cutaneous amyloidosis may be associated with local injections of human (recombinant) insulin. One should therefore also consider this diagnosis when finding tumours at sites where insulin has been injected. PMID- 20308713 TI - Tamsulosin and hyperglycaemia in patients with diabetes. PMID- 20308714 TI - Tryps after adventurous trips. PMID- 20308717 TI - Acute liver failure. AB - Acute liver failure is a rare but often catastrophic illness affecting the liver and multiple organ systems. Patients with acute liver failure require a multidisciplinary approach for adequate management. With improved critical care and the availability of liver transplantation, survival has significantly improved. Hepatic encephalopathy, cerebral edema and infections are the most common complications of acute liver failure. The evaluation requires a diligent search for a specific etiology of the liver failure, since certain causes may respond well to specific pharmacological therapies. Acetaminophen and non acetaminophen drug-induced hepatotoxicity account for more than 50% of cases of acute liver failure. Assessment of prognosis frequently (at least on a daily basis) by using various prognostic tools, allows the treating team to decide whether or not to proceed with urgent liver transplantation. Artificial liver support devices are still in evaluation and not ready for use in clinical practice. While it is determined whether or not there is sufficient hepatic regeneration, the care of the patient with acute liver failure revolves around managing the dysfunction of multiple extra hepatic systems. PMID- 20308718 TI - Endoscopic band ligation versus propranolol for the primary prophylaxis of variceal bleeding in cirrhotic patients with high risk esophageal varices. AB - BACKGROUND: Gastroesophageal variceal bleeding is a common complication of portal hypertension. Current guidelines recommend thorn-blockers for primary prophylaxis. However, evidence suggests that endoscopic variceal ligation (EVL) reduce bleeding episodes. AIMS: To compare endoscopic EVL with propranolol (PPL) for primary prophylaxis of variceal bleeding. METHODS: We conducted a randomized controlled trial. Over a 9-year period, 75 patients with cirrhosis and high-risk esophageal varices (HREV) were recruited and allocated to EVL (n=39) or PPL (n=36). Primary outcome was variceal bleeding. Secondary outcomes were survival, source of bleeding and serious adverse events. Analyses were made by intention-to treat. RESULTS: Baseline characteristics were similar. Medium follow-up was 1647+/-1096 days. complete follow-up was achieved in 85% of patients. Variceal bleeding occurred in 12% of EVL and in 25% of PPL group (p=0.17). The actuarial risks of bleeding after 2 years were similar in both groups. Overall mortality was 51% in EVL and 33% in PPL group (p=0.17). Patients in the EVL group showed a lower rate of esophageal variceal bleeding (5.1% v/s 25%, p=0.027) and a higher rate of subcardial variceal bleeding compared with PPL group (7.7% v/s 0%, p=0.027). Serious adverse events related to EVL occurred in 2 patients, including 1 death. CONCLUSIONS: The present study supports that PPL should be considered the first choice in primary prophylaxis of variceal bleeding offering similar effects and lower severe adverse events compared with EVL. PMID- 20308719 TI - Multimodal therapy for hepatocellular carcinoma: a complementary approach to liver transplantation. AB - OBJECTIVE: To evaluate the survival benefit of multimodal therapy for the treatment of HCC. BACKGROUND: Orthotopic liver transplantation (OLT) is considered the treatment of choice for selected patients with hepatocellular carcinoma (HCC). However, donor organ shortages and patients whose HCCs exceed OLT criteria require consideration of alternate therapeutic options such as hepatic resection, radiofrequency ablation (RFA), ethanol injection (EI), transarterial chemoembolization (TACE), and chemotherapy (CTX). This study was performed to evaluate the survival benefit of multimodal therapy for treatment of HCC as complementary therapy to OLT. METHODS: A retrospective review was conducted of HCC patients undergoing therapy following multidisciplinary review at our institution from 1996 . 2006 with a minimum of a 2 year patient follow-up. Data were available on 247/252 patients evaluated. Relevant factors at time of diagnosis included symptoms, hepatitis B (HBV) and C (HCV) status, antiviral therapy, Child-Pugh classification, portal vein patency, and TNM staging. Patients underwent primary treatment by hepatic resection, RFA, EI, TACE, CTX, or were observed (best medical management). Patients with persistent or recurrent disease following initial therapy were assessed for salvage therapy. Survival curves and pairwise multiple comparisons were calculated using standard statistical methods. RESULTS: Mean overall survival was 76.8 months. Pairwise comparisons revealed significant mean survival benefits with hepatic resection (93.2 months), RFA (66.2 months), and EI (81.1 months), compared with TACE (47.4 months), CTX (24.9 months), or observation (31.4 months). Shorter survival was associated with symptoms, portal vein thrombus, or Child-Pugh class B or C. HCV infection was associated with significantly shorter survival compared with HBV infection. Antiviral therapy was associated with significantly improved survival in chronic HBV and HCV patients only with earlier stage disease. CONCLUSION: Multimodal therapy is effective therapy for HCC and may be used as complementary treatment to OLT. PMID- 20308720 TI - Distribution of HCV genotypes and HCV RNA viral load in different regions of Mexico. AB - BACKGROUND AND AIM: To identify the geographic distribution of hepatitis C virus (HCV) genotypes and HCV RNA viral load in a large number of HCV-infected carriers in Mexico. METHODS: Patients with chronic hepatitis C (n = 8,802) were studied to identify HCV genotype using an immune line probe assay in samples shown previously to be positive for viral RNA by an RT-PCR test. Baseline HCV RNA was also evaluated. RESULTS: Genotype 1 accounted for 70.3%, genotype 2 for 21.8%, genotype 3 for 7.2%, genotype 4 for 0.3%, and genotype 5 for 0.1% of all cases; coinfection was present in 0.3%. Overall, Genotype 1 was the most prevalent Genotype. Regionally, genotype 1 occurred more frequently in the North-East, North, and Center- East regions of Mexico; genotype 2 was more prevalent in the South, East, and Peninsula regions; and genotype 3 was more prevalent in the North and North-West regions. Only 22.4% of patients with genotype 1 were classified in the low HCV RNA viral load category, and the distribution of this genotype did not differ significantly between regions. CONCLUSION: The prevalence of HCV genotypes and viral load in Mexico was 70.3% for genotype 1, but only 22.4% of these patients had a low HCV viral load. Distribution was not uniform in Mexico, with greater frequency of genotype 2 in South, East and Peninsula Regions and Genotype 3 in North and North-West Regions. PMID- 20308721 TI - Effects of TIPS on global end-diastolic volume and cardiac output and renal resistive index in ICU patients with advanced alcoholic cirrhosis. AB - The transjugular porto-systemic stent-shunt (TIPS) reduces portal pressure in cirrhotic patients and is used as a nonsurgical treatment for refractory ascites, recurrent variceal hemorrhage or hepatorenal syndrome. There are concerns regarding a negative impact on cirrhotic cardiomyopathy and deterioration of hyperkinetic circulatory dysfunction. We analyzed a prospectively maintained database containing hemodynamic data on cirrhotic ICU patients. Hemodynamic monitoring was performed using transpulmonary thermodilution (PiCCO, Pulsion Medical Systems, Munich, Germany). Renal perfusion was assessed by Doppler ultrasound during studies of portal and TIPS perfusion before and after the procedure. Complete data sets of 8 patients (4 male, 4 female, age 60 years (52 67), Child-Pugh-Turcotte score 10 (8-12)) were available. After TIPS, there was a substantial increase of GEDVI (646 ml/m2 (580-737) to 663 mL/m2 (643-792); p=0.036) that was even more pronounced at 24 hours (716 mL/m2 (663-821); P=0.012). CI increased from 3.3 L/min/m2 (3.1-4.2) to 3.9 L/min/m2 (3.6-5.3) (p=0.012) and 3.9 L/min/m2 (3.7-5.2) (p=0.017), respectively. There was a significant decrease of renal RI from 0.810 (0.781-0.864) to 0.746 (0.710-0.798) (p=0.028) and a transient increase of fractional excretion of sodium. SVRI (1737 dyn*s/cm5/m2 (1088 . 2115) vs. 1917 dyn*s/cm5/m2 (1368-2177) was not significantly altered immediately after TIPS but decreased to 1495 dyn*s/cm5/m2 (833- 1765) at 24 hours (p=0.036). There were no significant changes of mean arterial pressure (MAP). In conclusion, TIPS resulted in a pronounced increase of central blood volume. The observed hemodynamic effects are compatible with a preload driven increase of cardiac output and secondary decreases in SVRI and RI. PMID- 20308722 TI - Efficacy, tolerability and safety in the treatment of chronic hepatitis C with combination of PEG-Interferon - Ribavirin in daily practice. AB - BACKGROUND: Efficacy and safety of Pegylated Interferon alfa (PegIFN)-Ribavirin (RBV) for the treatment of chronic hepatitis C (CHC) in routine clinical practice seems to be comparable with results of randomized-controlled trials. AIMS: To evaluate the efficacy, tolerability and safety of CHC treatment with PegIFN + RBV in .real world. patients in Argentina and to analyze factors associated with SVR. METHODS: Medical records of patients treated according to current guidelines from 2001 to 2008 were reviewed. RESULTS: 235 patients were included and 80.8% completed treatment. Discontinuation occurred in 7.6% due to adverse events (AE), and 1.2% dropped-out treatment. Overall SVR was 60.8%. Multivariate analysis demonstrated that being naive (p 0.031) and low basal viral load (p 0.006) were associated with SVR, whereas F3-F4 (p 0.001) and elevated ALT (p 0.023) were associated with non-response. 80% of planned doses completed was associated with 74% SVR (p <0.001). At least one AE was reported in 93.6% of the patients: neutropenia in 27.6%, thrombocytopenia in 15.3%, anemia in 38.7%, psychiatric symptoms in 63.4%, thyroid dysfunction in 10.2%. CONCLUSION: Efficacy, tolerability and safety of treatment of CHC in daily practice in Argentina are similar to those reported in randomized controlled trials. PMID- 20308723 TI - High ghrelin and obestatin levels and low risk of developing fatty liver. AB - AIM: Obesity and insulin resistance are associated with nonalcoholic fatty liver disease (NAFLD). It was recently reported that the ratio between levels of ghrelin and obestatin is also associated with obesity and insulin resistance. We investigated the association between the ghrelin/obestatin ratio and NAFLD. METHODS: This cross-sectional study included 98 subjects (51 NAFLD patients and 47 controls). Anthropometric, metabolic and biochemical variables were measured and serum concentrations of ghrelin and obestatin were determined. Logistic regression analyses (univariate and multivariate) were conducted to determine whether NAFLD was associated with ghrelin and obestatin levels and the ghrelin/obestatin ratio. RESULTS: We studied 51 NAFLD cases and 47 controls. Men comprised 82% of cases and 61% of controls. The mean ages of the groups differed significantly. Body mass index (P < 0.001), waist circumference (P < 0.001) and WHR (P < 0.001) were significantly greater in the NAFLD group than in the control group. The NAFLD group had higher mean fasting glucose level (P = 0.001), HOMA-IR index (P < 0.001) and triglyceride level (P < 0.001) than the controls. Ghrelin and obestatin concentrations were classed according to tertiles. Multivariate analysis revealed a negative correlation between ghrelin and obestatin levels and an overweight status, obesity and metabolic syndrome. Ghrelin and obestatin were evaluated in multivariate logistic regression analysis, they had a protective effect against hepatic steatosis after controlling for potential confounders. CONCLUSION: Serum ghrelin and obestatin concentrations are correlated with a low risk of developing NAFLD. However, ghrelin/obestatin ratio was not correlated with NAFLD. PMID- 20308724 TI - Hepatotoxicity due to rifampicin, isoniazid and pyrazinamide in patients with tuberculosis: is anti-HCV a risk factor? AB - BACKGROUND AND RATIONALE: Among the adverse events related to tuberculosis treatment, hepatotoxicity is the most serious, and recognition of risk factors for it is essential to achieve successful therapy. The aim of the study is to evaluate the role of anti-HCV as a risk factor for hepatotoxicity in hospitalized patients under tuberculosis treatment with rifampicin, isoniazid and pyrazinamide (RHZ). METHODS: Historical cohort study carried out at Hospital Sanatorio Partenon, from 1998 to 2006. Patients aged 18 years or older, tested for anti HCV, who presented normal pre-treatment aminotransferases (AST, ALT) and bilirrubin and who used RHZ during hospitalization were included in the study. Individuals who used anti-tuberculosis drugs six months prior to hospitalization, had clinical evidence of chronic liver disease or showed previous history of hepatotoxicity to RHZ were excluded. RESULTS: A sample of 534 patients was studied. The incidence of hepatotoxicity was 8.8% (n = 47). After univariate analysis, the following variables were associated to hepatotoxicity: anti-HIV positive, anti-HCV positive, use of antiretroviral therapy and high doses of rifampicin and isoniazid per kg of body weight (p < 0.05). When Cox regression was performed, anti-HIV positive [RR = 2.3 (IC(95% )1.2-4.1); p = 0.008] and high doses of isoniazid per kg of body weight [RR = 1.3 (IC(95%) 1.1-1.7); p = 0.016] remained independently associated to development of hepatotoxicity. CONCLUSIONS: In conclusion, the anti-HIV positive and high doses of isoniazid were considered independent risk factors for hepatotoxicity due to RHZ esqueme in the present study. Though univariate analysis showed that anti-HCV was associated to the outcome, it was not identified as an independent risk factor for hepatotoxicity related to the use of RHZ when the analysis was controlled to HIV. PMID- 20308725 TI - Hepatoblastoma. Clinical experience at a single institution using the Siopel staging system. AB - BACKGROUND: Staging in Hepatoblastoma has recently become controversial. In developing countries diagnosis occurs mostly in advanced stages under these circumstances, we propose another option that can be considered of prognostic value. METHOD: A retrospective analysis of cases diagnosed with Hepatoblastoma (HB), treated in a single Institution, in nine years was conducted. Chemotherapeutic regimens were analyzed, as well as the number of courses administered and response to treatment. RESULTS: Thirty-two patients were studied. Patients had symptoms from 1 to 25 weeks before diagnosis. SIOP stratification was used, finding 12 cases in PRETEXT II, 6 cases in PRETEXT III, and 14 cases in PRETEXT IV. No single case was identified in PRETEXT I. CONCLUSIONS: When comparing survival using the PRETEXT system, SIOP and our study showed marked differences. These results may not be comparable due to differences in tumor volume among the same PRETEXT stratification. We believe that tumor volume is related to prognosis. PMID- 20308726 TI - Methimazole-induced hypothyroidism causes alteration of the REDOX environment, oxidative stress, and hepatic damage; events not caused by hypothyroidism itself. AB - Our objective was to compare, over a time-course, markers of oxidative stress, the REDOX environment, and the antioxidant enzymatic system in the liver of rats with methimazole- or thyroidectomy-caused hypothyroidism. METHODS: We used 60 male Wistar rats divided into four groups: 1) the euthyroid, which received only tap water, 2) false thyroidectomy, which received the surgery and postoperative treatment, 3) thyroidectomy-caused hypothyroidism, which had the thyroid gland removed and a parathyroid reimplant, and 4) methimazole-caused hypothyroidism in rats that received 60 mg/kg/d of the antithyroid drug in drinking water. Five rats of the euthyroid and methimazole-caused hypothyroidism groups were killed at the end of the first, second, third, and fourth week after treatment, and five rats of false thyroidectomy and thyroidectomy-caused hypothyroidism groups were killed at the end of the second and eighth week after the surgical procedure. Each liver was removed and stored at -70 degrees C until oxidative stress, REDOX environment, and antioxidant enzymatic system markers were tested. We also made a histological study at the end of the treatment. RESULTS: The histological study revealed that only the methimazole-caused hypothyroidism caused cell damage. This damage is associated with an increase of oxidative stress markers that were not compensated for by the antioxidant system. The catalase activity is reduced and this allows H2O2-caused damage. In conclusion methimazole causes cell damage in the liver, whereas hypothyroidism per se does not cause hepatic-cell damage. PMID- 20308727 TI - Adult live donor liver transplantation: routine, commonplace, standard care for end stage liver disease (we hope). PMID- 20308728 TI - Hepatic lymphoma in a post renal transplant patient with chronic hepatitis B. PMID- 20308729 TI - Macro-AST in an asymptomatic young patient. PMID- 20308730 TI - Actinomycotic liver abscess: a rare complication of colonic diverticular disease. AB - We present the first case of hepatic actinomycosis requiring both medical and surgical intervention due to liver dissemination from a primary colonic abscess. A 52-year-old white male had a computerised (CT) abdominal scan following an episode of collapse and was found to have peri-colonic and hepatic abscesses. Prior to this episode, he suffered with a two month history of fever, unexplained weight loss, and anaemia suggesting possible malignancy. He was treated with both radiological and surgical drainage of the abscesses, alongside the antibiotic cover and underwent an anterior colonic resection with primary anastomosis. There have been no previous reports of an actinomycotic liver abscess complicating colonic diverticular abscess. A multi- team approach is recommended when disseminated actinomycotic infection is encountered. PMID- 20308731 TI - Pitfall alveolar echinococcosis in non-endemic areas. Alveolar echinococcosis migrating northward. AB - Alveolar echinococcosis of the liver can be mistaken as a liver tumor. The occurrence of the fox tapeworm echinococcus multilocularis is increasing in formerly unaffected European regions. As a consequence, alveolar echinococcosis is becoming an important differential diagnosis in Eastern and Northern Europe. PMID- 20308732 TI - Endovascular treatment of a hepatic artery aneurysm causing chronic abdominal pain; a case report. AB - BACKGROUND: Aneurysms of the visceral arteries are rare but potentially lethal lesions. We describe a case of a successful endovascular exclusion of a hepatic artery aneurysm in a patient that suffered from chronic abdominal pain. CASE REPORT: A 68-year old man presented with chronic abdominal pain that had existed for 10 months. A diagnostic contrast-enhanced CT scan showed an 18 mm atherosclerotic aneurysm of the hepatic artery. When other pathology was excluded the aneurysm was excluded using an ePTFE-covered nitinol stentgraft. Post deployment angiograms showed a complete exclusion of the aneurysm. The abdominal complaints immediately resolved. After a follow-up period of 18 months patient had a patent endograft and remained free of symptoms. CONCLUSIONS: Small hepatic artery aneurysms may cause chronic recurrent abdominal pain and can be safely excluded using a covered stentgraft. PMID- 20308733 TI - Liver involvement in severe human influenza a H1N1. AB - Influenza A is a disease caused by a RNA virus, member of the orthomyxoviridae family. The influenza infection is characterized primarily by pulmonary affection that may advance to an acute pulmonary respiratory failure course. Hepatic involvement is not frequent and accounts for < 3% of all cases. We describe two patients with acute Influenza A H1N1 infection who developed hepatic involvement. Needle core liver biopsy of one of the patient revealed only micro and macrovesicular steatosis. PMID- 20308734 TI - Shortened therapy for genotype 1 hepatitis C virus. The final answer? PMID- 20308735 TI - Wake-up call for sleep disorders in developing nations. PMID- 20308736 TI - Sleep apnoea's detriment: part of the proof is in the lipids. PMID- 20308737 TI - Hyperlipidaemia in patients with sleep-related breathing disorders: prevalence & risk factors. AB - BACKGROUND & OBJECTIVES: several studies have shown a close relationship between obstructive sleep apnoea (OSA) and dyslipidaemia. This study was designed to clarify the relationship of metabolic dysfunctions in sleep related-breathing disorders (SRBD), including OSA and simple snoring. The end point was to determine the prevalence of hyperlipidaemia and hyperuricaemia in SRBD. Factors contributing to hyperlipidaemia and hyperuricaemia in SRBD were also evaluated. METHODS: Outpatients >20 yr old with complaint of habitual snoring were prospectively enrolled. All patients underwent an overnight polysomnography (PSG) in a sleep laboratory and blood assay after overnight fasting. The factors of gender, age, body mass index (BMI), apnoea-hypopnoea index (AHI), and desaturation index (DI) were recorded in the PsG report. A logistic regression analysis was conducted to investigate the relationship between metabolic dysfunctions and these factors. RESULTS: Of the 275 patients (88.4% male), 236 (85.8%) were diagnosed with OSA (AHI>5/h). The mean (+/- SD) of age, BMI, AHI, and DI were 44.2 +/- 11.4 yr, 27.4 +/- 4.0 kg/m(2), 37.9 +/- 30.6/h, and 21.2 +/- 23.2/h, respectively. The overall prevalence of hypercholesterolaemia, hypertriglyceridaemia, and hyperuricaemia in this study was 61.1, 55.3, and 25.8 per cent, respectively. Logistic regression analysis revealed that DI was a significant independent factors contributing to hypercholesterolaemia [odds ratio (OR)=1.016, P=0.010, 95% confidence interval (CI)=1.004-1.028] and hypertriglyceridaemia (OR=1.021, P=0.002, 95% CI=1.008-1.034). INTERPRETATION & CONCLUSIONS: The data of the present study support a high prevalence of hyperlipidaemia in SRBD. DI may be a determining factor contributing to hyperlipidaemia in SRDB. Underdiagnosis of hyperlipidaemia in SRBD is a critical problem. PMID- 20308738 TI - Overview of sleep & sleep disorders. AB - Sleep is defined on the basis of behavioural and physiological criteria dividing it into two states: non rapid eye movement (NREM) sleep which is subdivided into three stages (N1, N2, N3); and rapid eye movement (REM) sleep characterized by rapid eye movements, muscle atonia and desynchronized EEG. Circadian rhythm of sleep-wakefulness is controlled by the master clock located in the suprachiasmatic nuclei of the hypothalamus. The neuroanatomical substrates of the NREM sleep are located principally in the ventrolateral preoptic nucleus of the hypothalamus and those of REM sleep are located in pons. A variety of significant physiological changes occur in all body systems and organs during sleep as a result of functional alterations in the autonomic and somatic nervous systems. The international classification of sleep disorders (ICSD, ed 2) lists eight categories of sleep disorders along with appendix A and appendix B. The four major sleep complaints include excessive daytime sleepiness, insomnia, abnormal movements or behaviour during sleep and inability to sleep at the desired time. The most important step in assessing a patient with a sleep complaint is obtaining a detailed history including family and previous histories, medical, psychiatric, neurological, drug, alcohol and substance abuse disorders. Some important laboratory tests for investigating sleep disorders consist of an overnight polysomnography, multiple sleep latency and maintenance of wakefulness tests as well as actigraphy. General physicians should have a basic knowledge of the salient clinical features of common sleep disorders, such as insomnia, obstructive sleep apnoea syndrome, narcolepsy-cataplexy syndrome, circadian rhythm sleep disorders (e.g., jet leg, shift work disorder, etc.) and parasomnias (e.g., partial arousal disorders, REM behaviour disorder, etc.) and these are briefly described in this chapter. The principle of treatment of sleep disorders is first to find cause of the sleep disturbance and vigorously treat the co morbid conditions causing the sleep disturbance. If a satisfactory treatment is not available for the primary condition or does not resolve the problem, the treatment should be directed at the specific sleep disturbance. Most sleep disorders, once diagnosed, can be managed with limited consultations. The treatment of primary sleep disorders, however, is best handled by a sleep specialist. An overview of sleep and sleep disorders viz., Basic science; international classification and approach; and phenomenology of common sleep disorders are presented. PMID- 20308739 TI - Circadian rhythm sleep disorders. AB - Circadian rhythm sleep disorders are common conditions manifested as misalignment between the sleep period and the physical/social 24-h environmental cycle. Delayed sleep phase (typical in adolescents) and advanced sleep phase (frequent in the elderly), situations in which the sleep period is displaced to a later or earlier time, respectively, are the two most prevalent circadian rhythm sleep disorders. There are, however, nine possible diagnoses of clinical interest. Since light is the main cue used in synchronizing the biological clock, blind individuals and night-shift/rotating-shift workers are more prone to develop circadian rhythm sleep disorders. In this article, the circadian rhythm syndromes included in the new International Classification of Sleep Disorders are reviewed as well as the most recent guidelines for diagnosis and treatment. PMID- 20308740 TI - Central sleep apnoea. AB - Central sleep apnoea (CSA) is characterized by the cessation of breathing during sleep due to absent ventilatory drive and may be associated with symptoms of insomnia, excessive daytime sleepiness or frequent arousals. Central apnoeas occur through two pathophysiologic patterns, either post- hyperventilation or post-hypoventilation. The prevalence of CSA is dependent on the population being studied, the predominant risk factors being elderly age group and co-morbid conditions.Data regarding the racial distribution of this disorder are very limited. CSA may be a clinical marker of underlying medical disorders, including cardiac or neurological disease, with resultant significant morbidity and mortality. Given that the underlying pathogenesis remains poorly understood, therapeutic options are currently limited to empiric treatment with PAP devices and rudimentary attempts at pharmacologic therapy with respiratory stimulant drugs and/or oxygen/carbon dioxide gas supplementation as well as treating the underlying cause. The long-term impact of CSA on health and mortality needs further clarification. Future research should be aimed at elucidating the physiologic determinants and consequences of central breathing instability in populations of different age groups, gender and racial descent, as a prerequisite to the development of novel therapeutic interventions in the different populations. PMID- 20308741 TI - Obstructive sleep apnoea: definitions, epidemiology & natural history. AB - Obstructive sleep apnoea (OSA) is increasingly being recognized as an important health issue in the last two to three decades. It is characterized by frequent episodes of upper airway collapse during sleep, causing recurrent arousals, intermittent hypoxaemia, sleep fragmentation and poor sleep quality. There is accumulating evidence that OSA is being considered as an independent risk factor for hypertension, glucose intolerance / diabetes mellitus, cardiovascular diseases and stroke, leading to increased cardiometabolic morbidity and mortality. The prevalence rates of OSA have been estimated in the range of 2 to 10 per cent worldwide, and the risk factors for obstructive sleep apnoea include advanced age, male sex, obesity, family history, craniofacial abnormalities, smoking and alcohol consumption. The common clinical presenting symptoms are heavy snoring, witnessed apnoeas and daytime hypersomnolence, which would help to identify the affected individuals. With increasing awareness of this disease entity and associated complications in our society, there have been increased referrals to sleep physicians or expertise for further investigations and diagnostic evaluation. Early recognition and treatment of obstructive sleep apnoea may prevent from adverse health consequences. Some of the epidemiological aspects of obstructive sleep apnoea in adults are reviewed. PMID- 20308742 TI - Epidemiology of adult obstructive sleep apnoea syndrome in India. AB - There is a paucity of published Indian studies on the prevalence and risk factors of obstructive sleep apnoea (OSA) in adults. The limited published literature, however, does not suggest significant differences in the prevalence and risk factors for OSA and obstructive sleep apnoea syndrome (OSAS) as compared to western studies. Well designed studies are required from all parts of India. Patients should be screened carefully before referring them to costly investigations such as overnight polysomnography. With the background of increasing urbanization, fast growing economy and changes in lifestyle, India will have an epidemic of obesity. Therefore, future studies on the association of OSA and metabolic syndrome should carefully evaluate confounding effect of obesity on metabolic abnormalities in patients with OSA. PMID- 20308744 TI - Consequences of obstructive sleep apnoea. AB - A plethora of medical consequences have been associated with the syndrome of obstructive sleep apnoea (OSA). These are global, affecting nearly every body function, and have been related to two key pathophysiological findings in sleep apnoea: repetitive falls in oxyhaemoglobin saturation during sleep, and recurrent arousals from sleep which terminate apnoea episodes. Sufferers of OSA may experience daytime sleepiness, which has been measured both subjectively using the Epworth Sleepiness Scale and the Stanford Sleepiness Scale, but also objectively, using Multiple Sleep Latency Testing, Maintenance of Wakefulness testing, and the Oxford Sleep Resistance test. In addition to the loss of alertness, sleep apnoea contributes to memory deficits, reduced vigilance, impaired executive function, increased risk for automobile and occupational accidents, and decreased quality of life.Importantly, afflicted individuals experience improvements in these outcomes with treatment. Taken together, this evidence forms a compelling basis to identify and treat latent cases of sleep apnoea. Not only do patients have the opportunity to achieve improvements in these outcomes and health-related quality of life, but the enormous economic burden that untreated apnoea imposes on the health care system may be eased. PMID- 20308745 TI - Cardiovascular consequences of obstructive sleep apnoea. AB - Obstructive sleep apnoea (OSA) is a form of sleep disordered breathing with a high prevalence rate and is often underdiagnosed. OSA is associated with hypertension, coronary artery disease, stroke, peripheral vascular disease, heart failure, and arrhythmias. The presence of OSA may be a strong predictor of fatal cardiovascular events in patients with cardiovascular disease (CVD). Increased sympathetic drive, activation of metabolic and inflammatory markers, and impaired vascular function are some of the proposed mechanisms that could explain the association between OSA and cardiovascular diseases. Understanding these mechanisms is important for identifying treatment strategies. The presence of OSA should be considered in clinical practice, especially in patients with CVD. Randomized intervention studies are needed to establish whether early identification and treatment of OSA patients reduces cardiovascular morbidity. PMID- 20308746 TI - Sleep & the metabolic syndrome. AB - Sleep is an essential part of our daily living, and sleep disturbances may intervene with the biological and physiological processes in human body leading to the development of metabolic dysfunction. Short sleep duration and poor sleep quality have adverse effects on metabolism and hormonal processes, contributing to increased cardiovascular risk. Obstructive sleep apnoea is a chronic condition characterized by repetitive upper airway collapse during sleep, causing intermittent hypoxaemia, recurrent arousals and sleep fragmentation. Sleep disturbances can increase sympathetic activity, provoke systemic inflammation and oxidative stress, and impair vascular endothelial function. Obstructive sleep apnoea is increasingly recognized to be an independent cardiovascular risk factor. There is intense research interest in the association between obstructive sleep apnoea and the metabolic syndrome - the constellation of inter-related metabolic derangements including central obesity, hypertension, insulin resistance and dyslipidaemia, which appears to directly promote the development of atherosclerosis. The underlying pathophysiologic pathways or mechanistic links between obstructive sleep apnoea and metabolic syndrome have not been well delineated. This article reviews the current knowledge of the relationship between sleep disturbances, sleep-disordered breathing and the metabolic syndrome in adults. PMID- 20308743 TI - Pathophysiology & genetics of obstructive sleep apnoea. AB - Obstructive sleep apnoea (OSA) is a highly prevalent condition with proven neurocognitive and cardiovascular consequences. OSA patients experience repetitive narrowing or collapse of the pharyngeal airway during sleep. Multiple factors likely underlie the pathophysiology of this condition with considerable inter-individual variation. Important risk factors for OSA include obesity, male gender, and ageing. However, the mechanisms underlying these major risk factors are not well understood. We briefly review the state-of-the-art knowledge regarding OSA pathogenesis in adults and highlight the potential role of genetics in influencing key OSA pathophysiological traits. PMID- 20308747 TI - Diagnosis of sleep apnoea: some critical issues. AB - Rather than describing a method for determining which patients should be labelled as having a disease, sleep apnoea, this review describes assessment as a process for deciding whom to investigate, what degree of sleep apnoea they have, how important their symptoms are, whether symptoms are likely attributable to sleep apnoea, and what sort of treatment to offer, if any. Beginning with identifying patients at risk and use of clinical prediction rules, the review covers (i) measurement and implications of the apnoeahypopnoea index; (ii) distinguishing central from obstructive apnoeas; (iii) significance of associated periodic limb movements; (iv) the controversy about the use of portable monitors instead of laboratory polysomnography; (v) evaluation of symptoms associated with sleep apnoea; and (vi) the important role of trials of treatment. PMID- 20308748 TI - Evaluation of the upper airway in obstructive sleep apnoea. AB - The evaluation of the upper airway (UA) includes the physical examination of pharyngeal structures and a number of imaging techniques that vary from the mostly used lateral cephalometry and computed tomography to more sophisticated methods such as tri-dimensional magnetic resonance image (MRI). Other complex techniques addressing UA collapsibility assessed by measurement of pharyngeal critical pressure and negative expiratory pressure however are not routinely performed. These methods provide information about anatomic abnormalities and the level of pharyngeal narrowing or collapse while the patient is awake or asleep. Data suggest that individual patients have different patterns of UA narrowing. So, the best method for evaluating obstruction during obstructive events remains controversial. In general, in clinical practice physical examination including a systematic evaluation of facial morphology, mouth, nasal cavity and the pharynx as well as simple imaging techniques such as nasopharyngoscopy and cephalometry have been more routinely utilized. Findings associated with obstructive sleep apnoea (OSA) are UA narrowing by the lateral pharyngeal walls and enlargements of tonsils, uvula and tongue. Additionally cephalometry identifies the most significant craniofacial characteristics associated with this disease. MRI studies demonstrated that lateral narrowing of UA in OSA is due to parapharyngeal muscle hypertrophy and/or enlargement of non adipose soft tissues. The upper airway evaluation has indubitably contributed to understand the pathophysiology and the diagnosis of OSA and snoring. Additionally, it also helps to identify the subjects with increased OSA risk as well as to select the more appropriate modality of treatment, especially for surgical procedures. PMID- 20308749 TI - Treatment of obstructive sleep apnoea. AB - Obstructive sleep apnoea (OSA) is a prevalent disorder with significant co morbidities. Presently only rarely, treatments for obstructive sleep apnoea are curative. More typically, this is a disease that requires lifelong intervention and commitment from both the patients and healthcare providers. In light of the commitments, there is no uniform approach to treating sleep apnoea. Rather, approach to treatment of OSA should be governed by disease severity, symptoms and health risk and by which approach will work best for in a specific patient. It is equally important to identify and treat contributors to obstructive sleep apnoea severity, including obesity and endocrine disorders. In this sense, treating the patient with obstructive sleep apnoea requires a long-term partnership between patient and sleep medicine healthcare providers. With a strong partnership, obstructive sleep apnoea may be effectively treated in growing numbers of patients. PMID- 20308751 TI - Continuous positive airway pressure therapy: new generations. AB - Continuous positive airway pressure (CPAP) is the treatment of choice for obstructive sleep apnoea syndrome (OSAS). However, CPAP is not tolerated by all patients with OSAS and alternative modes of pressure delivery have been developed to overcome pressure intolerance, thereby improving patient comfort and adherence. Auto-adjustable positive airway pressure (APAP) devices may be utilised for the long-term management of OSAS and may also assist in the initial diagnosis of OSAS and titration of conventional CPAP therapy. Newer modalities such as C-Flex and A-Flex also show promise as treatment options in the future. However, the evidence supporting the use of these alternative modalities remains scant, in particular with regard to long-term cardiovascular outcomes. In addition, not all APAP devices use the same technological algorithms and data supporting individual APAP devices cannot be extrapolated to support all. Further studies are required to validate the roles of APAP, C-Flex and A-Flex. In the interim, standard CPAP therapy should continue as the mainstay of OSAS management. PMID- 20308750 TI - Adherence to continuous positive airway pressure treatment for obstructive sleep apnoea: implications for future interventions. AB - Adherence to continuous positive airway pressure (CPAP) treatment for obstructive sleep apnoea (OSA) is a critical problem. Poor adherence (30-60%) to CPAP is widely recognized as a significant limiting factor in treating OSA, reducing the overall effectiveness of the treatment and leaving many OSA patients at heightened risk for co-morbid conditions, impaired function and quality of life. The extant literature examining adherence to CPAP provides critical insight to measuring adherence outcomes, defining optimal adherence levels, and predicting CPAP adherence. This research has revealed salient factors that are associated with or predict CPAP adherence and may guide the development of interventions to promote CPAP adherence. Over the past 10 years, intervention studies to promote CPAP adherence have incorporated a multitude of strategies including education, support, cognitive behavioural approaches, and mixed strategies. This review of the current status of research on CPAP adherence will (i) synthesize the extant literature with regard to measuring, defining, and predicting CPAP adherence; (ii) review published intervention studies aimed at promoting CPAP adherence; and (iii) suggest directions for future empiric study of adherence to CPAP that will have implications for translational science. Our current understanding of CPAP adherence suggests that adherence is a multi-factorial, complex clinical problem that requires similarly designed approaches to effectively address poor CPAP adherence in the OSA population. PMID- 20308752 TI - Surgical treatment of snoring & obstructive sleep apnoea. AB - Obstructive sleep apnoea (OSA) syndrome is a potentially serious disorder affecting millions of people around the world. Many of these individuals are undiagnosed while those who are diagnosed, often exhibit poor compliance with nightly use of continuous positive airway pressure (CPAP), a very effective nonsurgical treatment. Various surgical procedures have been proposed to manage and, in some cases, treat OSA. In this article we review methods used to assess the sites of obstruction and a number of surgical procedures designed to address OSA. Effective surgical management of OSA depends upon developing a complete database and determining different levels of obstruction, which may include nasal, nasopharyngeal, oropharyngeal, and hypopharyngeal/retrolingual, or a combination of these sites. A systematic approach to clinical evaluation, treatment planning and surgical management is recommended and is likely to result in more predictable outcomes. Surgical treatment may involve various procedures that are performed in different stages depending on the patient's sites of obstruction. The most commonly performed procedures include nasal reconstruction, uvulopalatopharyngoplasty (UPPP), advancement genioplasty, mandibular osteotomy with genioglossus advancement, and hyoid myotomy and suspension. In more severe cases, maxillomandibular advancement (MMA) with advancement genioplasty may be indicated. Even after appropriate surgical treatment, some patients may demonstrate continued obstruction with associated symptoms. Published indications for surgical treatment include an elevated respiratory disturbance index (RDI) with excessive daytime somnolence (EDS), oxygen desaturations below 90 per cent, medical co-morbidities including hypertension and arrhythmias, anatomic abnormalities of the upper airway and failure of medical treatment. The success of surgery in OSA is generally measured by achieving a (RDI) of less than 5, improvement of oxygen nadir to 90 per cent or more with no desaturations below 90 per cent and quality of life improvements with elimination or significant reduction of OSA symptoms. From a practical point of view, achieving these goals may be extremely difficult without patients' cooperation, most notably in the realm of weight loss and maintenance of a healthy lifestyle. PMID- 20308753 TI - Sleep disordered breathing in patients with chronic kidney disease. AB - The prevalence of sleep-disordered breathing (SDB) in the advanced chronic kidney disease (CKD) patient population has been estimated to be more than 50 per cent. SDB is associated with episodic upper airway obstruction or cessation of breathing during sleep leading to repetitive episodes of hypoxaemia, hypercapnia, and sleep fragmentation, activation of the sympathetic nervous system, endothelial dysfunction, oxidative stress, and inflammation. Clinical consequences of this disorder may include excessive daytime sleepiness, depressed mood, cognitive impairment, hypertension, as well as increased risk for cardiovascular disease and metabolic dysregulation. SDB may also contribute substantially to the daytime sleepiness, poor quality of life, and high rate of cardiovascular disease in CKD patients. Although the causal links between CKD and SDB remain speculative, there are multiple factors related to fluid overload and azotaemia that may contribute to the increased propensity to SDB. Renal transplantation, nocturnal automated peritoneal dialysis and nocturnal haemodialysis have been found to be associated with a reduction in the severity of SDB when compared to conventional forms of dialysis. Nocturnal dialysis modalities may facilitate further understanding of the pathophysiology of SDB as well as provide therapeutic alternatives for patients with both kidney failure and SDB. SDB is an important but often overlooked public health problem in the CKD patient population. Early diagnosis and treatment of SDB may provide better quality of life and attenuate the cardiovascular risk of morbidity and mortality in these patients. PMID- 20308754 TI - Sleep disordered breathing in women of childbearing age & during pregnancy. AB - Obstructive sleep apnoea (OSA) affects 11 per cent of pre-menopausal women though it often remains undetected. Women may present differently than men, and the classic findings of snoring, witnessed apnoeas and sleepiness may not be observed. Factors which predispose to OSA include polycystic ovarian syndrome, obesity, retromicrognathia, and hypothyroidism. OSA may contribute to neurocognitive dysfunction, depression, hypertension and metabolic syndrome. Emerging evidence indicates that snoring and OSA increase during pregnancy. For normal women with normotensive, low-risk pregnancies the prevalence of OSA is very low. Among normotensive pregnant women with high risk pregnancies, the prevalence of OSA is high and is even higher among those with gestational hypertension/preeclampsia during pregnancy. Incident snoring, which is a marker for OSA, is associated with an increased risk of developing gestational hypertension. Recent studies indicate that OSA per se is an independent risk factor for gestational hypertension/pre-eclampsia and may contribute to other poor obstetrical outcomes. The diagnostic test of choice for OSA is a polysomnography with electroencephalogram. Milder degree of disease than what is usually considered clinically significant among men or non-pregnant women appears to be relevant for foetomaternal outcomes. There seems to be benefit for blood pressure control to treating even milder degrees of OSA with CPAP, both acutely and over the 9 months of pregnancy. Chronic hypertensive women should be strongly considered for diagnosis and treatment of OSA prior to or beginning as early as possible in pregnancy to help maintain blood pressure control. Increasing awareness of OSA among maternal health care providers is important given the potential benefits for pregnancy and other health-related outcomes associated with identification and treatment of OSA. PMID- 20308755 TI - Sleep disorders in the elderly. AB - Nearly half of older adults report difficulty initiating and maintaining sleep. With age, several changes occur that can place one at risk for sleep disturbance including increased prevalence of medical conditions, increased medication use, age-related changes in various circadian rhythms, and environmental and lifestyle changes. Although sleep complaints are common among all age groups, older adults have increased prevalence of many primary sleep disorders including sleep disordered breathing, periodic limb movements in sleep, restless legs syndrome, rapid eye movement (REM) sleep behaviour disorder, insomnia, and circadian rhythm disturbances. The present review discusses age-related changes in sleep architecture, aetiology, presentation, and treatment of sleep disorders prevalent among the elderly and other factors relevant to ageing that are likely to affect sleep quality and quantity. PMID- 20308756 TI - Sleep disordered breathing in children. AB - Sleep disordered breathing (SDB) is increasingly being recognised as a cause of morbidity even in young children. With an estimated prevalence of 1 to 4 per cent, SDB results from having a structurally narrow airway combined with reduced neuromuscular tone and increased airway collapsibility. SDB in children differs from adults in a number of ways, including presenting symptoms and treatment. Presentation may differ according to the age of the child. Children have a more varied presentation from snoring and frequent arousals to enuresis to hyperactivity. Those with Down syndrome, midface hypoplasia or neuromuscular disorders are at higher risk for developing SDB. First line definitive treatment in children involves tonsillectomy and adenoidectomy. Rapid maxillary expansion, allergy treatment and continuous positive airway pressure (CPAP) are other options. As untreated SDB results in complications as learning difficulties, memory loss and a long term increase in risk of hypertension, depression and poor growth, it is important to diagnose SDB. PMID- 20308758 TI - Parasomnias: an overview. AB - Parasomnias are abnormal experiences or behaviours that occur during sleep and can be subdivided into disorders of arousal, disorders of rapid eye movement (REM) sleep or other parasomnias. Diagnosis rests on a thorough clinical evaluation with supporting data from a full polysomnography with time synchronized video. While the prognosis for arousal disorders is generally excellent, the diagnosis of REM behaviour disorder (RBD) is more ominous and associated with neurodegenerative disorders, and as such, requires routine neurological surveillance. The cornerstone of treatment for all parasomnias is adequate patient and bed partner education. Data supporting pharmacologic therapy are limited but clonazapam for RBD has been reported to be effective in up to 89 per cent of patients. PMID- 20308759 TI - Narcolepsy: clinical features, co-morbidities & treatment. AB - Narcolepsy is a neurologic illness that typically begins in the second and third decades of life. It is chronic in nature and negatively impacts the quality of life of affected patients. The classic presentation is a tetrad of excessive daytime sleepiness, cataplexy, sleep paralysis, and hypnagogic hallucinations. The exact cause remains unknown, but there is significant evidence that hypocretin deficiency plays an integral role. Some primary conditions that result in secondary narcolepsy include traumatic brain injury, congenital disorders, tumours, and strokes. Some medical and psychiatric disorders share characteristics of narcolepsy, at times leading to diagnostic inaccuracy. Other sleep disorders are commonly co-morbid. Diagnosis relies on patient history and objective data gathered from polysomnography and multiple sleep latency testing. Treatment focuses on symptom relief through medication, education, and behavioural modification. Both classic pharmacological treatments as well as newer options have significant problems, especially because of side effects and abuse potential. Novel modalities are being examined to expand options for treatment. PMID- 20308757 TI - Diagnosis, prevalence, pathways, consequences & treatment of insomnia. AB - Insomnia is a highly prevalent sleep disorder that frequently occurs in its acute form and occurs at a rate of approximately 10 per cent in its chronic form in many countries. There is a high prevalence of insomnia in a variety of medical and psychiatric conditions for which insomnia often serves as a risk factor. The aetiology and pathophysiology of insomnia is such that several factors may predispose individuals for or precipitate and/or perpetuate the condition. Both sedative-hypnotic and cognitivebehavioural interventions exist for insomnia and each type of intervention have substantial levels of empirical support for their efficacy. PMID- 20308760 TI - Nocturnal hypoventilation - identifying & treating syndromes. AB - Nocturnal hypoventilation is a common feature of disorders affecting the function of the diaphragm or central respiratory drive mechanisms. The ensuing change in gas exchange is initially confined to rapid eye movement (REM) sleep, but over time buffering of the raised carbon dioxide produces a secondary depression of respiratory drive that will further reduce ventilation not only during sleep but eventually during wakefulness as well. Failure to identify and treat nocturnal hypoventilation results in impairments in daytime function, quality of life and premature mortality. While some simple daytime tests of respiratory function can identify at risk individuals, these cannot predict the nature or severity of any sleep disordered breathing present. Nocturnal monitoring of gas exchange with or without full polysomnography is the only way to comprehensively assess this disorder, especially in the early stages of its evolution. Non invasive ventilation used during sleep is the most appropriate approach to reverse the consequences of nocturnal hypoventilation, although continuous positive airway pressure (CPAP) may be effective in those individuals where a significant degree of upper airway obstruction is present. When appropriately selected patients use therapy on a regular basis, significant improvements in quality of life, exercise capacity and survival can be achieved, irrespective of the underlying disease process. PMID- 20308761 TI - Growth performance of affluent Indian preschool children: a comparison with the new WHO growth standard. AB - This study was conducted to evaluate the nutritional status of 2-5 year old affluent, urban children using the new WHO 2006 standards. A cross-sectional, multicentric preschool-based study was conducted on 1493 children (727 boys). Mean Z scores for height, weight, body mass index and weight for height( 0.75(1.1), -0.59(1.1), -0.19(1.22) and -0.26(1.18), respectively) were below the WHO standard median. PMID- 20308762 TI - Prevalence of hypertension among schoolchildren in Shimla. AB - This cross sectional study was done to find the prevalence of sustained hypertension and prehypertension among school children aged 11-17 years. A total of 1085 apparently healthy students from rural and urban schools in hills of northern India were examined using standard methods. Students with blood pressures above the 90th centile were reexamined after four weeks. The mean BMI of the students was 17.5 +/- 2.7 kg/m2, 5 (0.4%) were obese, and 39 (3.5%) overweight. After two evaluations, hypertension was identified in 62 (5.9%) children and prehypertension in 130 (12.3%). Urban and rural children had comparable rates of elevated BP (hypertension and prehypertension). Rates of elevated BP were significantly higher (46.5% vs 17%, P<0.001) among those with high BMI (overweight and obese) compared to those with normal BMI. In conclusion, nearly 20% of the school children had elevated blood pressures. PMID- 20308763 TI - Intravenous Adrenaline for Shock in Neonates. AB - Dopamine and dobutamine have been widely used to treat shock with variable success in newborns. In this retrospective data analysis, we report on the use of adrenaline in 20 neonates with birth asphyxia and shock that was refractory to dopamine and dobutamine. We concluded that adrenaline is a safe and effective drug that can be used as an add-on therapy to dopamine and/or dobutamine in newborns with shock secondary to birth asphyxia. PMID- 20308765 TI - Effect of oral zinc supplementation on the growth of preterm infants. AB - OBJECTIVE: To compare the effect of oral zinc supplementation on growth of preterm infants. DESIGN: Randomized controlled trial. SETTING: Dhaka Shisu Hospital (Tertiary care hospital). SUBJECTS: 100 appropriate for date preterm infants weighing between 1000 to 2500 g were randomized to receive zinc and multivitamin supplement (Group I; n=50) or only multivitamin supplement (Group II). INTERVENTION: Zinc supplementation was given 2mg/kg/day for 6 weeks along with multivitamin in Group I and only multivitamin to Group II. PRIMARY OUTCOME VARIABLE: Increment of weight and length. RESULTS: At enrollment, serum zinc (62.1 +/- 12.4 ug/dL in Group I and 63.1 +/- 14.6 ug/dL in Group II) and hemoglobin levels (14.9 +/- 2.4 g/dL in Group I and 14.4 +/- 1.7 g/dL in Group II) were almost similar in both groups. Serum zinc levels were in lower limit of normal range. After supplementation, serum zinc and hemoglobin levels were significantly higher in Group I (105 +/- 16.5 ug/dL) than Group II (82.2 +/- 17.4 ug/dL) (P<0.05). Weight, length and head circumference were comparable in both groups at enrollment. Significant differences in weight gain and increment in length were found in first and second follow up between two groups but OFC increments were not significant (P>0.05). Reduction of morbidity was apparent in zinc supplemented group. No serious adverse effect was noted related to supplementation therapy. CONCLUSION: Zinc supplementation for preterm low birth weight babies is found effective to enhance the growth in early months of life. PMID- 20308766 TI - Transient tone abnormalities in high risk infants and cognitive outcome at five years. AB - OBJECTIVE: to identify transient tone abnormalities and determine its prevalence in high risk infants and their cognitive outcome at 5 years. DESIGN: prospective cohort observational study. SETTING: high risk infants discharged from a level II neonatal unit in a 12 month period, and followed upto 5 years. METHODS: High risk infants and normal controls were assessed for abnormalities of tone using the method described by Amiel Tison at 3, 6, 9, 12 months. An IQ by Stanford Binet method and a preschool inventory by Ayres, Bobath was done at 5 years. Those infants who had normal tone at 6 and 12 months were called normal high risk (HR) group and those who had abnormalities at 6 months, which disappeared at 12 months, were called the transient tone abnormalities (TTA) group. RESULTS: out of 190 high risk infants, 113 were normal HR and 67 (35.2%) were labeled as TTA. Ten infants with cerebral palsy had abnormal tone throughout the first year. Controls had normal tone throughout the follow-up period. Although there was no difference in the IQ of the TTA group (98.5 +/- 12.4) and the normal HR (99.1 +/- 13.1) group, it was significantly less (P=0.04) than that of controls (106.1 +/- 9.1). Preschool inventory in TTA children showed poor language development (P=0.014). CONCLUSION: many of the tone abnormalities detected at 6 months resolve by 12 months, hence a hasty diagnosis of cerebral palsy should not be made. High risk infants with transient tone abnormalities have a normal cognitive outcome at 5 years, except for poor language skills. PMID- 20308767 TI - Diagnostic re-evaluation of children with congenital hypothyroidism. AB - OBJECTIVES: To investigate the causes of congenital hypothyroidism in children more than 3 years of age and to document the frequency of transient vs permanent hypothyroidism. DESIGN: Hospital based observational study. SETTING: Pediatric endocrine clinic of a medical college. PATIENTS: Children over 3 years of age, on treatment for congenital hypothyroidism. INTERVENTION: Thyroid function test (TFT) and thyroid ultrasound was done. Children with agenesis or hemiagenesis in thyroid ultrasound were identified. In children with normal or equivocal thyroid ultrasound, thyroxine was stopped and followed. Children with abnormal TFT on follow up had thyroid scintigraphy with or without potassium perchlorate discharge, after which, thyroid hormone supplement was restarted. Children who remained euthyroid on follow up were labeled as having transient hypothyroidism. MAIN OUTCOME MEASURE: Proportion of children with transient hypothyroidism. RESULTS: Among 36 children studied (20 boys and 16 girls), eighteen (50%) had transient hypothyroidism and fifteen (41.7%) had thyroid agenesis. There was one with hemiagenesis, one with ectopic thyroid and another with dyshormonogenesis (2.8% each). Initial TSH level at the time of diagnosis was higher in permanent hypothyroidism as compared with transient group (83.0 +/- 31.6 vs 47.0 +/- 33.1 mIU/mL; P= 0.002). CONCLUSIONS: Thyroid hormone supplementation could be discontinued in 50% of children diagnosed with congenital hypothyroidism. PMID- 20308768 TI - School absenteeism among children and its correlates: a predictive model for identifying absentees. AB - OBJECTIVES: To determine the magnitude of absenteeism and its correlates and to develop a model to predict absenteeism in school children. DESIGNS: A cross sectional study. SETTING: three government schools in Delhi. PARTICIPANTS: 704 students, aged 10 to15 years. METHODS: students were registered and interviewed using a pre designed questionnaire. The frequency and causes of school absenteeism were ascertained by school records, leave applications and one months recall. The factors were subjected to univariate analysis and a stepwise multiple logistic regression analysis and a predictive model was developed. RESULTS: The average absenteeism of a student over 6 months was 14.3+/-10.2 days (95% CI 13.5 15.0). 48% children absented themselves for more than two days per month on an average. The main factors associated with school absenteeism were younger age, male sex, increasing birth order, lower levels of parental education and income, school truancy, school phobia and family reasons. The discriminating ability of the predictive model developed was 92.4% CONCLUSIONS: it is possible to identify potential absentees in school children. PMID- 20308769 TI - Impact of two regimens of vitamin D supplementation on calcium - vitamin D - PTH axis of schoolgirls of Delhi. AB - OBJECTIVE: To determine the efficacy of supplementation with oral vitamin D3 (cholecalciferol) on bone mineral biochemical parameters of school-going girls. SETTING: Government school (government-aided) and Private school (fee paying) in Delhi. DESIGN: Randomized controlled trial. INTERVENTION: Cholecalciferol granules (60,000 IU) orally with water, either once in two months (two-monthly D3 group) or once a month (one-monthly D3 group) for one year. PARTICIPANTS: 290 healthy schoolgirls (6-17 y), 124 from lower socioeconomic strata (LSES) (attending government schools) and 166 from upper socioeconomic strata (USES) (attending private schools). OUTCOME MEASURES: Serum 25(OH)D, calcium, phosphorus, parathyroid hormone, and alkaline phosphatase levels at 6 and 12 months after start of supplementation. RESULTS: At baseline, 93.7% schoolgirls were vitamin D deficient [25(OH)D<50 nmol/L]. While significant increase in serum calcium and decrease in alkaline phosphatase levels was noted in both groups with both interventions, PTH response was inconsistent. In LSES subjects, two-monthly D3 and one-monthly D3 supplementation resulted in a significant increase in serum 25(OH)D levels by 8.3 nmol/L and 11.0 nmol/L, respectively at 6 months (P<0.05). Similarly, the increase in the two intervention arms in USES subjects was 10.5 nmol/L and 16.0 nmol/L, respectively (P<0.05). In both groups, this increase in serum 25(OH)D levels persisted at 12 months (P<0.05). Despite supplementation with 60,000 IU of Vitamin D3 (monthly or two-monthly), only 47% were vitamin D sufficient at the end of one year. CONCLUSIONS: 60,000 IU of cholecalciferol, monthly or two-monthly, resulted in a significant increase in serum 25(OH)D levels in vitamin D deficient schoolgirls. PMID- 20308770 TI - Potential neuroprotective effects of acupuncture stimulation on diabetes mellitus in a global ischemic rat model. AB - Acupuncture (ACU) is known to be effective in ischemia treatment, and glutamate (GLU) excitotoxicity is an important factor in neuronal cell death. We observed the effect of ACU on cerebral blood flow (%CBF) and DeltaGLU (the changes in GLU release) in the ischemic stroke rat model of diabetic mellitus (DM). A global ischemia was induced using the eleven-vessel occlusion (11-VO) method in 14 Sprague-Dawley rats (DM), which were randomly divided into two groups: the control group and the ACU-treatment group. Extracellular DeltaGLU was assessed using an intra-cerebral biosensor system measuring 256 samples per second, simultaneously with %CBF and electroencephalogram. ACU stimulation was applied to ACU points GB34 and GB39 during the ischemic period. Twenty-three diagnostic parameters were proposed first for a detailed analysis of changes in %CBF and GLU release during ischemia/reperfusion. ACU rats showed a significant decrease in ischemic (p < 0.05) and reperfusion %CBF (p < 0.0001) than control rats, and a significantly larger decrease in ischemic DeltaGLU (p < 0.05) and peak level of reperfusion DeltaGLU (p < 0.005) than control rats. From these results, we suggest that ACU stimulation is responsible for the potential protection of neurons through suppression of %CBF response in the increased plasma osmolality and extracellular DeltaGLU in diabetic rats under ischemic conditions. PMID- 20308771 TI - The morphological classification of heartbeats as dominant and non-dominant in ECG signals. AB - Surface electrocardiography (ECG) is the art of analyzing the heart's electrical activity by applying electrodes to certain positions on the body and measuring potentials at the body surface resulting from this electrical activity. Usually, significant clinical information can be obtained from analysis of the dominant beat morphology. In this respect, identification of the dominant beats and their averaging can be very helpful, allowing clinicians to carry out the measurement of amplitudes and intervals on a beat much cleaner from noise than a generic beat selected from the entire ECG recording. In this paper a standard clustering algorithm for the morphological grouping of heartbeats has been analyzed based on K-means, different signal representations, distance metrics and validity indices. The algorithm has been tested on all the records of the MIT-BIH Arrhythmia Database (MIT-BIH AD) obtaining satisfying performances in terms of averaged dominant beat estimation, but the results have not been fully satisfactory in terms of sensitivity and specificity. In order to improve the clustering accuracy, an ad hoc algorithm based on a two-phase decision tree, which integrates additional specific knowledge related to the ECG domain, has been implemented. Similarity features extracted from every beat have been used in the decision trees for the identification of different morphological classes of ECG beats. The results, in terms of dominant beat discrimination, have been evaluated on all annotated beats of the MIT-BIH AD with sensitivity = 99.05%, specificity = 93.94%, positive predictive value = 99.32% and negative predictive value = 91.69%. Further tests have shown a very slight decrement of the performances on all detected beats of the same database using an already published QRS detector, demonstrating the validity of the algorithm in real unsupervised clustering situations where annotated beat positions are not available but beats are detected with a high-performance beat detector. PMID- 20308772 TI - How to detect and reduce movement artifacts in near-infrared imaging using moving standard deviation and spline interpolation. AB - Near-infrared imaging (NIRI) is a neuroimaging technique which enables us to non invasively measure hemodynamic changes in the human brain. Since the technique is very sensitive, the movement of a subject can cause movement artifacts (MAs), which affect the signal quality and results to a high degree. No general method is yet available to reduce these MAs effectively. The aim was to develop a new MA reduction method. A method based on moving standard deviation and spline interpolation was developed. It enables the semi-automatic detection and reduction of MAs in the data. It was validated using simulated and real NIRI signals. The results show that a significant reduction of MAs and an increase in signal quality are achieved. The effectiveness and usability of the method is demonstrated by the improved detection of evoked hemodynamic responses. The present method can not only be used in the postprocessing of NIRI signals but also for other kinds of data containing artifacts, for example ECG or EEG signals. PMID- 20308773 TI - ECG-based prediction of atrial fibrillation development following coronary artery bypass grafting. AB - In patients undergoing coronary artery bypass grafting (CABG) surgery, post operative atrial fibrillation (AF) occurs with a prevalence of up to 40%. The highest incidence is seen between the second and third day after the operation. Following cardiac surgery AF may cause various complications such as hemodynamic instability, heart attack and cerebral or other thromboembolisms. AF increases morbidity, duration and expense of medical treatments. This study aims at identifying patients at high risk of post-operative AF. Early prediction of AF would provide timely prophylactic treatment and would reduce the incidence of arrhythmia. Patients at low risk of post-operative AF could be excluded on the basis of the contraindications of anti-arrhythmic drugs. The study included 50 patients in whom lead II electrocardiograms were continuously recorded for 48 h following CABG. Univariate statistical analysis was used in the search for signal features that could predict AF. The most promising ones identified were P wave duration, RR interval duration and PQ segment level. On the basis of these, a nonlinear multivariate prediction model was made by deploying a classification tree. The prediction accuracy was found to increase over time. At 48 h following CABG, the measured best smoothed sensitivity was 84.8% and the specificity 85.4%. The positive and negative predictive values were 72.7% and 92.8%, respectively, and the overall accuracy was 85.3%. With regard to the prediction accuracy, the risk assessment and prediction of post-operative AF is optimal in the period between 24 and 48 h following CABG. PMID- 20308774 TI - An artificial vector model for generating abnormal electrocardiographic rhythms. AB - We present generalizations of our previously published artificial models for generating multi-channel ECG to provide simulations of abnormal cardiac rhythms. Using a three-dimensional vectorcardiogram (VCG) formulation, we generate the normal cardiac dipole for a patient using a sum of Gaussian kernels, fitted to real VCG recordings. Abnormal beats are specified either as perturbations to the normal dipole or as new dipole trajectories. Switching between normal and abnormal beat types is achieved using a first-order Markov chain. Probability transitions can be learned from real data or modeled by coupling to heart rate and sympathovagal balance. Natural morphology changes from beat-to-beat are incorporated by varying the angular frequency of the dipole as a function of the inter-beat (RR) interval. The RR interval time series is generated using our previously described model whereby time- and frequency-domain heart rate (HR) and heart rate variability characteristics can be specified. QT-HR hysteresis is simulated by coupling the Gaussian kernels associated with the T-wave in the model with a nonlinear factor related to the local HR (determined from the last n RR intervals). Morphology changes due to respiration are simulated by introducing a rotation matrix couple to the respiratory frequency. We demonstrate an example of the use of this model by simulating HR-dependent T-wave alternans (TWA) with and without phase-switching due to ectopy. Application of our model also reveals previously unreported effects of common TWA estimation methods. PMID- 20308775 TI - A comparison of the effects of fibre alignment of smooth and textured fibres in electrospun membranes on fibroblast cell adhesion. AB - A polyester polycaprolactone-based polyurethane elastomer (PU) and poly-(l lactide) (PLLA), two common biomaterials, were electrospun to produce membranes with fibres either randomly orientated or aligned. PU was used to produce membranes consisting of smooth fibres. PLLA was used to prepare fibres with a textured surface. Contact angle measurements of the PU and PLLA cast films reveal that they were both below 90 degrees and fully wetted in less than 60 s. These membranes were investigated for the effect of fibre topography and fibre alignment on cell adhesion, using mouse L929 fibroblasts. It was found that the alignment of electrospun fibres controls the directional spreading of fibroblast independent of fibre being smooth or textured. PMID- 20308776 TI - Biphasic calcium sulfate dihydrate/iron-modified alpha-tricalcium phosphate bone cement for spinal applications: in vitro study. AB - In this study, the cytocompatibility of new 'iron-modified/alpha-tricalcium phosphate (IM/alpha-TCP) and calcium sulfate dihydrate (CSD)' bone cement (IM/alpha-TCP/CSD-BC) intended for spinal applications has been approached. The objective was to investigate by direct-contact osteoblast-like cell cultures (from 1 to 14 days) the in vitro cell adhesion, proliferation, morphology and cytoskeleton organization of MG-63 cells seeded onto the new cements. The results were as follows: (a) quantitative MTT-assay and scanning electron microscopy (SEM) showed that cell adhesion, proliferation and viability were not affected with time by the presence of iron in the cements; (b) double immunofluorescent labeling of F-actin and alpha-tubulin showed a dynamic interaction between the cell and its porous substrates sustaining the locomotion phenomenon on the cements' surface, which favored the colonization, and confirming the biocompatibility of the experimental cements; (c) SEM-cell morphology and cytoskeleton observations also evidenced that MG-63 cells were able to adhere, to spread and to attain normal morphology on the new IM/alpha-TCP/CSD-BC which offered favorable substratum properties for osteoblast-like cells proliferation and differentiation in vitro. The results showed that these new iron-modified cement-like biomaterials have cytocompatible features of interest not only as possible spinal cancellous bone replacement biomaterial but also as bone tissue engineering scaffolds. PMID- 20308779 TI - Insights into the disappointing clinical trials of antioxidants in neurodegenerative diseases. PMID- 20308777 TI - Promoting successful cognitive aging: a comprehensive review. AB - Promoting successful cognitive aging is a topic of major importance to individuals and the field of public health. This review presents a coherent framework not only for evaluating factors, protective activities, and enhancing agents that have already been proposed, but also ones that will be put forward in the future. The promotion of successful cognitive aging involves the dual goals of preventing loss of information processing capacity and cognitive reserve, and enhancing brain capacity and cognitive reserve. Four major lines of evidence are available for evaluating whether a proposed factor promotes successful cognitive aging: 1) epidemiologic/cohort studies; 2) animal/basic science studies; 3) human "proof-of-concept" studies; and 4) human intervention studies. Each line of evidence has advantages and limitations that will be discussed. Through illustrative examples, we trace the ways in which each method informs us about the potential value of several proposed factors. Currently, lines of converging evidence allow the strongest case to be made for physical and cognitively stimulating activities. Although epidemiological data seem to favor the use of statins to lower the risk of dementia, more definitive recommendations await further randomized controlled studies. There is presently no clear evidence that antioxidants or Ginkgo biloba promote successful cognitive aging. The impact of resveratrol, fish oil, and a long list of other proposed agents needs to be determined. Clinicians remain well-positioned to identify and aggressively treat vascular risk factors, diabetes, sleep disorders, and other conditions that may reduce brain capacity, and to encourage activities that can build cognitive reserve. PMID- 20308780 TI - Osteopontin is increased in the cerebrospinal fluid of patients with Alzheimer's disease and its levels correlate with cognitive decline. AB - Inflammation is believed to play a role in Alzheimer's disease (AD). Osteopontin (OPN) is a molecule involved in macrophage recruitment and activation and implicated in neurodegeneration. In order to elucidate the role of OPN in AD, we evaluated its levels in serum and cerebrospinal fluid (CSF) of 67 AD patients, 46 frontotemporal dementia (FTD) patients, and 69 controls. We found that OPN levels: i) are significantly increased in the CSF of AD patients; ii) correlate with MMSE score; and iii) are higher in the early disease phases ( 2 years). These findings support a role of OPN in AD pathogenesis. PMID- 20308778 TI - Neuronutrition and Alzheimer's disease. AB - Alzheimer's disease (AD) is a complex neurological disorder resulting from both genetic and environmental factors with the latter being particularly important for the sporadic form of the disease. As such, diets rich in saturated fatty acids and alcohol, and deficient in antioxidants and vitamins appear to promote the onset of the disease, while diets rich in unsaturated fatty acids, vitamins, antioxidants, and wine likely suppress its onset. In addition, evidence suggests that diets rich in polyphenols and some spices suppress the onset of AD by scavenging free radicals and preventing oxidative damage. Metal ions are known to catalyze the production of free radicals and induce mental retardation or dementia, and several studies have also identified metals such as Pb, Fe, Al, Cu, and Zn in AD pathogenesis. While specific metal chelators have been tested for therapy, they have not been very successful, probably due to their late administration, i.e., after brain damage has been triggered. Since several dietary polyphenols are known to chelate metals, their routine use may also be protective against the onset of AD. In this review, we summarize beneficial dietary techniques in the fight against AD. PMID- 20308781 TI - Statin users without an APOE-epsilon4 allele have increased insulin resistance. AB - The present study examined the relationships among statin use, APOE genotype, and insulin resistance as measured by the homeostasis model assessment of insulin resistance (HOMA-IR) in healthy older adults. APOE epsilon4- (i.e., not having an epsilon4 allele) statin users had higher HOMA-IR values compared with epsilon4+/statin users (p=0.0169), and with non-users who were epsilon4- (p=0.0003) or epsilon4+ (p=0.0006). These results suggest that statin use may modulate insulin levels for individuals without an APOE epsilon4 allele. PMID- 20308783 TI - Follow-up study of susceptibility loci for Alzheimer's disease and onset age identified by genome-wide association. AB - Replication of genetic association findings in independent studies represents an important validation tool in the search for susceptibility genes for complex diseases such as Alzheimer's disease (AD). In a well-characterized memory-clinic based study comprising 1078 unrelated AD patients and 652 control individuals, we set out to replicate previously reported genome-wide association of four novel risk SNPs with AD and onset age, with first stage p-values ranging from 0.001 to 0.000004. We obtained evidence for association between rs179943, an intronic SNP in ATXN1 at 6p22.3, and affection status (OR = 0.63 (95% CI = 0.44-0.90; nominal p = 0.01)). Overall, our data provided independent support for association of at least one chromosomal locus with AD and warranted a more in-depth investigation of these regions for possible underlying functional variants. PMID- 20308782 TI - Leptin reduces pathology and improves memory in a transgenic mouse model of Alzheimer's disease. AB - We have previously reported anti-amyloidogenic effects of leptin using in vitro and in vivo models and, more recently, demonstrated the ability of leptin to reduce tau phosphorylation in neuronal cells. The present study examined the efficacy of leptin in ameliorating the Alzheimer's disease (AD)-like pathology in 6-month old CRND8 transgenic mice (TgCRND8) following 8 weeks of treatment. Leptin-treated transgenic mice showed significantly reduced levels of amyloid beta (Abeta){1-40} in both brain extracts (52% reduction, p= 0.047) and serum (55% reduction, p= 0.049), as detected by ELISA, and significant reduction in amyloid burden (47% reduction, p=0.041) in the hippocampus, as detected by immunocytochemistry. The decrease in the levels of Abeta in the brain correlated with a decrease in the levels of C99 C-terminal fragments of the amyloid-beta protein precursor, consistent with a role for beta -secretase in mediating the effect of leptin. In addition, leptin-treated TgCRND8 mice had significantly lower levels of phosphorylated tau, as detected by AT8 and anti-tau-Ser{396} antibodies. Importantly, after 4 or 8 weeks of treatment, there was no significant increase in the levels of C-reactive protein, tumor necrosis factor alpha, and cortisol in the plasma of leptin-treated TgCRND8 animals compared to saline-treated controls, indicating no inflammatory reaction. These biochemical and pathological changes were correlated with behavioral improvements, as early as after 4 weeks of treatment, as recorded by a novel object recognition test and particularly the contextual and cued fear conditioning test after 8 weeks of treatment. Leptin-treated TgCRND8 animals significantly outperformed saline treated littermates in these behavioral tests. These findings solidly demonstrate the potential for leptin as a disease modifying therapeutic in transgenic animals of AD, driving optimism for its safety and efficacy in humans. PMID- 20308784 TI - Reduced homocysteine-thiolactonase activity in Alzheimer's disease. AB - Elevated plasma homocysteine (Hcy) is a risk factor for Alzheimer's disease (AD). Bleomycin hydrolase (BLH), a thiol-dependent enzyme that has Hcy-thiolactonase (HTase) and aminopeptidease (APase) activities, has also been implicated in Alzheimer's disease (AD). In order to examine its role in AD, BLH activities were measured in postmortem brain tissue from twelve AD patients and twelve control patients who died from non-neurological causes. We found that HTase and APase activities in human brain extracts were strongly correlated and sensitive to the thiol reagent iodoacetamide, indicating that they are associated with BLH. Both activities were significantly decreased in brain tissue extracts from AD patients relative to controls (7.6 +/- 4.2 vs. 13.5 +/- 5.5 units, p= 0.003 for HTase, and 3.82 +/- 1.27 vs. 5.33 +/- 1.68 units, p=0.010 for APase). HTase and APase activities were positively correlated with N-linked protein Hcy, but not with tHcy, in AD and control brains. Levels of brain total Hcy and N-linked protein Hcy did not differ between AD cases and controls. These results suggest that diminished functional BLH activity could contribute to the pathology of AD. PMID- 20308785 TI - Early deficits in cortical control of swallowing in Alzheimer's disease. AB - The goal of this study was to determine whether functional changes in cortical control of swallowing are evident in early Alzheimer's disease (AD), before dysphagia (swallowing impairment) is evident. Cortical function was compared between an early AD group and a group of age-matched controls during swallowing. Swallowing oropharyngeal biomechanics examined from videofluoroscopic recordings were also obtained to more comprehensively characterize changes in swallowing associated with early AD. Our neuroimaging results show that the AD group had significantly lower Blood-Oxygen-Level-Dependent (BOLD) response in many cortical areas that are traditionally involved in normal swallowing (i.e., pre and postcentral gyri, Rolandic and frontal opercula). There were no regions where the AD group showed more brain activity than the healthy controls during swallowing, and only 13% of all active voxels were unique to the AD group, even at this early stage. This suggests that the AD group is not recruiting new regions, nor are they compensating within regions that are active during swallowing. In videofluoroscopic measures, the AD group had significantly reduced hyo-laryngeal elevation than the controls. Although, swallowing impairment is usually noted in the late stages of AD, changes in cortical control of swallowing may begin long before dysphagia becomes apparent. PMID- 20308786 TI - Intrathecal IgG synthesis in patients with alterations in the neurochemical dementia diagnostics. AB - Neurochemical Dementia Diagnostics (NDD), i.e., analysis of the cerebrospinal fluid (CSF) concentrations of amyloid-beta peptides and tau/phospho-tau proteins plays important role in the diagnosis of neurodegeneration and dementias. Several studies show alterations of these biomarkers in Alzheimer's disease (AD), however, only a few reports address alterations of other CSF biomarkers (albumin and immunoglobulins' quotients, cell count, lactate concentration, etc.) in the pathophysiology and diagnostic procedures of dementias. Therefore, we analyzed these biomarkers in patients diagnosed for dementia syndromes and carefully characterized with the state-of-the-art NDD analysis: Abeta1-42, Abetax-42, Abetax-42/x-40 ratio, tau, and ptau181. We found intrathecal IgG synthesis in 5 out of 112 patients showing alterations of the NDD biomarkers, and in four out of these five subjects, we could not find any satisfying reason for the intrathecal humoral response. In 25.9% of the patients with altered NDD biomarkers, we found an increased albumin quotient indicating a dysfunction of the blood-CSF barrier; however a similar figure of 25.2% was found in the group of patients without alterations in the NDD. Our findings suggest that at least some patients with increased CSF concentrations of tau/ptau proteins and decreased concentrations of Abeta{42} peptides show simultaneously CSF alterations found otherwise in neuroinflammatory processes. This, in turn, suggests that extended diagnosis should be performed in patients with "isolated" alterations of NDD biomarkers or intrathecal immunoglobulin synthesis. PMID- 20308788 TI - PP2A regulates tau phosphorylation directly and also indirectly via activating GSK-3beta. AB - Abnormal hyperphosphorylation of tau appears to be crucial in neurofibrillary degeneration in Alzheimer's disease (AD). Previous studies suggest that a down regulation of protein phosphatase 2A (PP2A), the major tau phosphatase in human brain, contributes to tau hyperphosphorylation in AD. However, the effects of PP2A down-regulation on site-specific tau hyperphosphorylation is not well understood. In the present study, we showed that PP2A dephosphorylated tau at several phosphorylation sites with different efficiencies. Among the sites studied, Thr205, Thr212, Ser214, and Ser262 were the most favorable sites, and Ser199 and Ser404 were the least favorable sites for PP2A in vitro. Inhibition of PP2A with okadaic acid in metabolically active rat brain slices caused inhibition of glycogen synthase kinase-3beta (GSK-3beta) via an increase in its phosphorylation at Ser9. GSK-3beta phosphorylated tau at many sites, with Ser199, Thr205, and Ser396 being the most favorable sites in cells. The overall alterations in tau phosphorylation induced by PP2A inhibition were the result of the combined effects of both reduced tau dephosphorylation due to PP2A inhibition directly and reduced phosphorylation by GSK-3beta due to its inhibition. Because the impacts of tau phosphorylation on its biological activity and on neurofibrillary degeneration are site-specific, this study provides a new insight into the role of PP2A down-regulation in neurofibrillary degeneration in AD. PMID- 20308787 TI - GLP-1 receptor stimulation reduces amyloid-beta peptide accumulation and cytotoxicity in cellular and animal models of Alzheimer's disease. AB - Type 2 (T2) diabetes mellitus (DM) has been associated with an increased incidence of neurodegenerative disorders, including Alzheimer's disease (AD). Several pathological features are shared between diabetes and AD, including dysfunctional insulin signaling and a dysregulation of glucose metabolism. It has therefore been suggested that not only may the two conditions share specific molecular mechanisms but also that agents with proven efficacy in one may be useful against the other. Hence, the present study characterized the effects of a clinically approved long-acting analogue, exendin-4 (Ex-4), of the endogenous insulin releasing incretin, glucagon-like peptide-1 (GLP-1), on stress-induced toxicity in neuronal cultures and on amyloid-beta protein (Abeta) and tau levels in triple transgenic AD (3xTg-AD) mice with and without streptozocin (STZ) induced diabetes. Ex-4 ameliorated the toxicity of Abeta and oxidative challenge in primary neuronal cultures and human SH-SY5Y cells in a concentration-dependent manner. When 11 to 12.5 month old female 3xTg AD mice were challenged with STZ or saline, and thereafter treated with a continuous subcutaneous infusion of Ex-4 or vehicle, Ex-4 ameliorated the diabetic effects of STZ in 3xTg-AD mice, elevating plasma insulin and lowering both plasma glucose and hemoglobin A1c (HbA1c) levels. Furthermore, brain levels of Abeta protein precursor and Abeta, which were elevated in STZ 3xTg-AD mice, were significantly reduced in Ex-4 treated mice. Brain tau levels were unaffected following STZ challenge, but showed a trend toward elevation that was absent following Ex-4 treatment. Together, these results suggest a potential value of Ex-4 in AD, particularly when associated with T2DM or glucose intolerance. PMID- 20308789 TI - Dysfunctional characteristics of circulating angiogenic cells in Alzheimer's disease. AB - Vascular senescence contributes to the progression of Alzheimer's disease (AD) and circulating angiogenic cells (CACs) participate in the maintenance of the endothelium. As a step toward the development endothelial regeneration therapies for AD, we investigated the functional characteristics of CACs in AD patients. We enrolled AD patients and non-demented risk factor control subjects after matching for age, sex, and Framingham risk score. CACs were cultured from peripheral blood samples taken from subjects and used for various ex vivo assays. CACs from AD patients showed reduced chemotaxis, increased senescence, reduced paracrine angiogenic activity, and altered gene expression patterns compared to CACs from risk factor (RF) controls. Addition of high concentration Abeta{1-42} (200, 2000 ng/mL) to the CAC culture reduced CAC counts and endothelial nitric oxide synthase/Akt phosphorylation and induced apoptosis. However, lower concentration of Abeta{1-42} (2, 20 ng/mL) failed to reduce the CAC counts. CACs from AD patients were more susceptible to the cytotoxic effect of Abeta{1-42} than CACs from RF controls. In summary, AD patients have intrinsic dysfunctions of CACs which provides an extended understanding of vascular endothelial pathogenesis in AD. PMID- 20308790 TI - Circulating angiogenic cells and Alzheimer's disease: contribution of the bone marrow to the pathogenesis of the disease. PMID- 20308791 TI - Anesthesia with isoflurane increases amyloid pathology in mice models of Alzheimer's disease. AB - There is a great interest in the environmental and genetic factors which modify the risk of Alzheimer's disease since the manipulation of these factors could help to change the prevalence and natural course of this disease. Among the first group, anesthesia and surgery have been considered as risk enhancers, based mostly on "in vitro" experiments and epidemiological studies. We have investigated the effects of repetitive anesthesia, twice a week, for 3 months, from 7 to 10 months of age, with isoflurane on survival, behavior, apoptosis in hippocampal cells, amyloid-beta (Abeta) peptide and tau patterns, chaperones and autophagy in WT and AbetaPP{swe} mice. We have found that AbetaPP{swe} mice treated with isoflurane have increased mortality, less responsiveness after anesthesia, long lasting reduced exploratory behavior, increased number of TUNEL{+} apoptotic cells, and increased ratio of pro-apoptotic proteins in hippocampus, reduced astroglial and increased microglial responses, increased Abeta aggregates and high molecular weight peptides, abnormal chaperone responses and reduced autophagy. These effects were not present in WT mice, suggesting that the deleterious impact of isoflurane on behavior, survival, neuronal cell death, and processing of proteins involved in neurodegeneration is restricted to subjects with increased susceptibility but does not affect normal subjects. PMID- 20308792 TI - Combined volumetry and DTI in subcortical structures of mild cognitive impairment and Alzheimer's disease patients. AB - The aim of this work was to investigate the hypothesis that multimodal MRI is able to detect the progressive disruption of volume and microstructure of subcortical structures in patients with amnestic mild cognitive impairment (a MCI) and mild Alzheimer's disease (AD) in comparison with healthy controls (CTRL). We combined volumetric and diffusion tensor imaging (DTI) techniques in a cross-sectional study including 30 a-MCI, 30 AD patients, and 30 age-matched CTRL. We employed a fully automated model-based segmentation algorithm on 3 Tesla MRI anatomical images and accurate coregistration of DTI to anatomical images to extract regional values of DTI parameters. Both the hippocampi significantly and progressively decreased in volume from CTRL through MCI to AD. Both the thalami showed a progressive and significant decrease in volume from CTRL to AD. Mean diffusivity (MD) values increased progressively across the three groups in the bilateral hippocampus, amygdala, and in the right caudate. No differences in fractional anisotropy (FA) values were found. Two distinct but overlapping patterns of progression of structural (i.e., atrophy) and microstructural (i.e., MD increase) damage were observed. Particularly, the pattern of atrophy was mirrored by the increasing value of the averaged MD, which provided a further indicator of subtle tissue disruption in the hippocampal structure in mild AD patients. Combining different MRI modalities can allow identifying sensitive indicators of the subtle pathogenic mechanisms that occur in subcortical areas of AD patients. PMID- 20308793 TI - The Society for Neuroscience 2009 meeting report, part 2. PMID- 20308795 TI - The relationship between serum uric acid level and metabolic syndrome: differences by sex and age in Taiwanese. AB - BACKGROUND: Metabolic syndrome (MetS) and hyperuricemia are important risk factors for cardiovascular disease. However, findings regarding the relationship between serum uric acid (UA) level and components of MetS have been inconsistent. This study was performed to explore the potential value of UA level as a marker of MetS among male and female Chinese of different ages. METHODS: A total of 5896 subjects (2960 females and 2936 males) were recruited from the Department of Health Management at the Chang Gung Medical Center. Hyperuricemia was defined as a serum UA value >7.0 mg/dL for males or >6.0 mg/dL for females. MetS was defined according to the criteria of the Adult Treatment Panel III, as modified for Chinese subjects. Serum UA was used to differentiate MetS and to calculate epidemiological indices by means of discriminate analysis and logistic regression. RESULTS: The sensitivity and specificity of serum UA concentration as a marker of MetS ranged from 55.2% to 61.4% and 61.9% to 68.4%, respectively. Subjects with high UA had a higher risk of MetS, with odds ratios ranging from 1.23 to 1.82 (P < 0.01). A positive correlation between serum UA and MetS was observed in both sexes. Serum UA and the occurrence of MetS rose with increasing age in females; in males, however, UA values did not vary with age. CONCLUSIONS: Serum UA is more closely associated with MetS in females than in males. High UA among middle-aged women may predict the development of MetS. PMID- 20308796 TI - Angiostatin inhibition of vascular endothelial growth factor-stimulated nitric oxide production in endothelial cells. AB - Angiostatin (AS), a proteolytic fragment of plasminogen, is a potent antiangiogenic factor. It was reported that AS attenuates the vasodilatory response to vascular endothelial growth factor (VEGF) in isolated interventricular arterioles. Here, we investigated the effect of AS on nitric oxide (NO) production in human umbilical vein endothelial cells (HUVECs). AS inhibited VEGF-stimulated NO production in a dose-dependent manner, whereas AS alone did not affect basal NO production. Disruption of kringle structures by reduction of disulfide bonds resulted in the loss of the inhibitory effect of AS on VEGF-stimulated NO production. To elucidate how AS might impair VEGF activation of endothelial NO synthase (eNOS), we further examined whether AS would affect Ca(2+)-dependent and -independent pathways of eNOS activation. AS had no effect on the transient increase in cytosolic Ca(2+) levels elicited by VEGF. In contrast, AS prevented VEGF-potentiated eNOS phosphorylation at Ser1177. These results clearly indicate that AS inhibits VEGF-stimulated NO production in HUVECs without affecting basal NO production. The kringle structures of AS are required for this effect, and impairment of Ser1177 phosphorylation of eNOS might be involved in the inhibition of VEGF-stimulated NO production by AS. PMID- 20308797 TI - Mexiletine reverses oxaliplatin-induced neuropathic pain in rats. AB - Oxaliplatin is a platinum-based chemotherapy drug characterized by the development of acute and chronic peripheral neuropathies. Mexiletine, an orally available Na(+)-channel blocker, has widely been used in patients with chronic painful diabetic neuropathy. In the present study, we examined the effect of mexiletine on oxaliplatin-induced neuropathic pain in rats. Mexiletine (100, but not 10 and 30, mg/kg, p.o.) completely reversed both mechanical allodynia and cold hyperalgesia induced by oxaliplatin (4 mg/kg, i.p., twice a week). Lidocaine (30, but not 3 and 10, mg/kg, i.p.) also significantly relieved both pain behaviors. These results suggest that mexiletine may be effective in relieving the oxaliplatin-induced neuropathic pain clinically. PMID- 20308798 TI - Aldosterone-sensitive nucleus tractus solitarius neurons regulate sensitivity of the baroreceptor reflex in high sodium-loaded rats. AB - We examined the role of aldosterone-sensitive neurons in the nucleus tractus solitarius (NTS) in the arterial baroreceptor reflex (baroreflex) function. Baroreflex sensitivity was induced by phenylephrine in high sodium-loaded rats and was significantly reduced. This baroreflex sensitivity was reversed by microinjection of the mineralocorticoid receptor (MR) antagonist eplerenone into the NTS. 11beta-Hydroxysteroid dehydrogenase type 2 neurons and MR were also identified in the NTS. These data suggest that the aldosterone-sensitive neurons in the NTS may have an important role in baroreflex function. PMID- 20308799 TI - Nerve growth factor suppresses prostate tumor growth. AB - Nerve growth factor (NGF) facilitates reinnervation of perivascular nerves that regulate vascular tone and blood flow. This study investigated whether NGF prevents tumor growth by promoting neuronal regulation of tumor blood flow. The growth rate of DU145 prostate carcinoma cells subcutaneously implanted into nude mice was significantly inhibited by subcutaneous NGF administration. Significant suppression of tumor growth continued after withdrawing NGF. NGF increased vascular smooth muscle cells in tumor tissues, but had no cytotoxic action on tumor cells in vitro. These results suggest that NGF prevents tumor growth via an indirect effect, probably innervation or maturation of the tumor neovasculature. PMID- 20308800 TI - Identification and characterization of rat RhoA gene promoter. AB - RhoA upregulation has been suggested in bronchial smooth muscles (BSMs) of asthmatic rats. Here, we cloned/characterized the 5'-promoter region of the rat rhoA. A transcription-initiation site was identified at 66-bp upstream of the reference sequence, GenBank-BC061732. Luciferase assay using interleukin-13 (IL 13)-stimulated cells revealed a significant promoter activity at 238- to 166-bp upstream of the transcription-initiation site, which contains a signal transducer and activation of transcription (STAT) 6-binding region. The IL-13-induced increase in luciferase activity was inhibited by a STAT6 inhibitor, AS1517499, or a Janus kinases (JAKs) inhibitor, JAK Inhibitor-I, but not by tyrphostin-AG490, WHI-P131, or tyrphostin-AG9 (selective JAK2, JAK3, and Tyk2 inhibitors, respectively). Thus, rat BSM rhoA expression may have causal relation to the IL 13-JAK1-STAT6 signaling. PMID- 20308801 TI - Involvement of platelet-derived growth factor-BB and its receptor-beta in hypoxia induced depression of excitatory synaptic transmission in the nucleus tractus solitarius of mice. AB - The role of platelet-derived growth factor (PDGF)-BB / PDGF receptor (PDGFR)-beta signal in inhibition of synaptic transmission by hypoxia is unclear. In the nucleus tractus solitarius neurons, hypoxia with N(2) or NaCN decreased the amplitude of excitatory postsynaptic currents (EPSCs) similarly in wild type (WT) and PDGFR-beta gene-knockout (KO) mice. Recovery of EP SCs after a high concentration of NaCN in KO mice was significantly faster than that in WT mice, while recovery after a low concentration of NaCN or N(2) was not different between both mice. These results suggest that the PDGF-BB / PDGFR-beta signal modulates the excitatory synaptic transmission during hypoxia. PMID- 20308802 TI - Internalization of constitutively active N111G MUTANT of AT1 receptor induced by angiotensin II-receptor antagonists candesartan, losartan, and telmisartan: comparison with valsartan. AB - Based on radioligand binding and signal transduction assays in our previous study, we have determined the binding pattern and functional efficacy of the constitutively active mutant N111G of angiotensin II type 1 (AT(1)) receptor. We have also shown that the N111G mutant induces homologous internalization through mediation of the AT(1)-receptor antagonist valsartan. In this study we demonstrated that other AT(1)-receptor antagonists, candesartan, losartan, and telmi-sartan, also stimulate internalization of N111G mutant receptor to the same extent. We further showed that the internalization pattern is also similar for all the AT(1)-receptor antagonists. PMID- 20308803 TI - Interactions of calmodulin with the multiple binding sites of Cav1.2 Ca2+ channels. AB - Although calmodulin binding to various sites of the Cav1.2 Ca(2+) channel has been reported, the mechanism of the interaction is not fully understood. In this study we examined calmodulin binding to fragment channel peptides using a semi quantitative pull-down assay. Calmodulin bound to the peptides with decreasing affinity order: IQ > preIQ > I-II loop > N-terminal peptide. A peptide containing both preIQ and IQ regions (Leu(1599) - Leu(1668)) bound with approximately 2 mol of calmodulin per peptide. These results support the hypothesis that two molecules of calmodulin can simultaneously bind to the C-terminus of the Cav1.2 channel and modulate its facilitatory and inhibitory activities. PMID- 20308804 TI - Effects of nicorandil on the cAMP-dependent Cl- current in guinea-pig ventricular cells. AB - In guinea-pig cardiomyocytes, a cAMP-dependent Cl(-) current (I(Cl,cAMP)) flows through a cardiac isoform of the cystic fibrosis transmembrane conductance regulator (CFTR), which belongs to a family of the ATP-binding cassette (ABC) proteins. Although several K(+)-channel openers and sulfonylurea ATP-sensitive K(+) (K(ATP))-channel blockers reportedly inhibit I(Cl,cAMP), effects of nicorandil on the Cl(-) current have not been evaluated. This study was conducted to examine the effects of nicorandil on I(Cl,cAMP) in isolated guinea-pig ventricular cells using patch clamp techniques. Nicorandil in concentrations higher than 300 microM enhanced the I(Cl,cAMP) preactivated by 0.1 microM isoproterenol. The isoproterenol-induced I(Cl,cAMP) was inhibited by 100 microM glibenclamide, but not by 100 microM pinacidil. SNAP (S-nitroso-N-acetyl-D,L penicillamine, 10 microM), a nitric oxide (NO) donor, similarly enhanced the isoproterenol-induced I(Cl,cAMP). However, SG-86, a denitrated metabolite possessing K(+ )channel-opening action, failed to enhance the Cl(-) current. When the I(Cl,cAMP) was activated by 3-isobutyl-1-methylxanthine (IBMX, 30 microM), either nicorandil or SNAP failed to enhance the isoproterenol-induced I(Cl,cAMP). Thus, nicorandil enhances I(Cl,cAMP) in guinea-pig cardiomyocytes through an increase in intracellular cGMP, although direct modulation of I(Cl,cAMP) by NO cannot be completely excluded. PMID- 20308805 TI - Cohort differences in health, functioning and physical activity in the young-old Finnish population. AB - BACKGROUND AND AIMS: A mixed picture emerges from the international literature about secular and cohort changes in the health and functioning of older adults. We conducted a repeated population based cross-sectional study to determine trends in health, functioning and physical activity in the young old Finnish population. METHODS: Representative samples of community-dwelling people aged 65 69 years in 1988 (n=362), 1996 (n=320) and 2004 (n=292) were compared in socio economic status, self-rated health, chronic diseases, memory problems, ability to carry out instrumental activities of daily living, physical activity, and five year mortality. RESULTS: Significant improvement in all the investigated modalities, except that of chronic diseases, was observed in the newer cohorts. In logistic regression analysis, after controlling for socioeconomic status and gender, cohort effects remained significant for memory problems, IADL difficulties and physical activity. Cox regression analyses showed significant improvement in survival when later cohorts were compared with the earlier ones. CONCLUSIONS: This study provides evidence of improving levels of socio-economic status, self-rated health, functioning, physical activity, and lower risk of mortality in the newer cohorts of the Finnish young-old, but this was not accompanied by a parallel diminution in chronic diseases. PMID- 20308806 TI - Someone asked for a "how-to" write editorial. PMID- 20308807 TI - Gaining the most from an older adult research interview. AB - The relationship between research and practice is increasingly important. The research interview is part of the foundation of quality research and evidence based practice decisions. Thorough preparation and planning is required for a successful research interview with an older adult. PMID- 20308808 TI - A "waiver" program that keeps Ohio elders at home: PASSPORT in home health care. PMID- 20308809 TI - When a for-profit acquires a nonprofit organization: lessons learned from one home health/hospice's experience. PMID- 20308810 TI - Development and implementation of an advanced wound management class: preparing for OASIS-C. AB - This article explains the process of developing a 10-week course entitled Advanced Wound Management, in preparation for the implementation of Outcome and Assessment Information Set-C (OASIS-C). The impetus for choosing wound management was the result of a Needs Assessment completed by the nursing staff. The wound management learning needs identified by the clinicians in the Needs Assessment were aligned with the organization's goal to prepare for OASIS-C. PMID- 20308811 TI - The use of electronic health information systems in home care: facilitators and barriers. AB - Electronic health information systems (EHIS) containing standardized assessment data (e.g., RAI-Home Care, Outcome and Assessment Information Set [OASIS]) hold considerable promise, but their potential has yet to be fully realized. Literature was searched for strategies on implementing and using EHIS, including barriers and facilitators of their use in home care. Results of this review will be discussed in terms of their implications for the future development and use of EHIS in home care, and for future research. PMID- 20308812 TI - OASIS-C, depression screening, and M1730: additional screening is necessary: the value of using standardized assessments. PMID- 20308813 TI - The Gatekeeper Program: proactive identification and case management of at-risk older adults prevents nursing home placement, saving healthcare dollars program evaluation. AB - The Gatekeeper Program is an innovative community and hospital partnership focused on prevention of premature nursing home placement. Utilizing trained volunteers, who come into contact with older adults through their everyday jobs, the program provides assistance to over 1600 older adults. Positive program outcomes include reducing emergency department (ED) and hospital admissions and a 14 million dollar savings in healthcare costs related to nursing home placement. PMID- 20308814 TI - Patient safety and medications in the home. PMID- 20308816 TI - Neuroanesthesiology update. AB - Recent literature contains many reports of value to clinicians providing anesthetic or intensive care for neurosurgical patients or patients experiencing, or at risk for, neurological impairment. We will review many of these articles, focusing on those that address intracranial hemorrhage, intracranial procedures, carotid endarterectomy, spine surgery, and the determinants of outcome in patients with evolving or new-onset neurologic disease. Additionally, we will review articles addressing neurotoxicity, neuroprotection, and nervous system monitoring. PMID- 20308817 TI - Emergence times are similar with sevoflurane and total intravenous anesthesia: results of a multicenter RCT of patients scheduled for elective supratentorial craniotomy. AB - BACKGROUND: Nearly every anesthetic agent has been used for craniotomy, yet the choice between intravenous or volatile agents has been considered an area of significant debate in neuroanesthesia. We designed a Randomized Clinical Trial to test the hypothesis that inhalation anesthesia (sevoflurane/remifentanil--group S) reduces emergence time by 5 minutes compared with intravenous anesthesia (propofol/remifentanil--group P) in patients undergoing neurosurgery for supratentorial neoplasms. METHODS: Adult ASA I-III elective patients were randomly assigned to group S or P. The primary outcome was time to reach an Aldrete test score (AS) of more than equal to 9; secondary outcomes were times to eyes opening (TEO) and extubation (ET), adverse events, intraoperative hemodynamics, brain relaxation score (BRS), opioid consumption, and diuresis. RESULTS: No significant differences were found between S (n=149) and P (n=153) treatments in primary outcomes: median time to reach AS=9 was 5 minutes (25th to 75th percentile 5 to 10 minutes in both groups, P > or = 0.05); and 15 minutes to reach AS=10 (P group 95% CI=10.3-19.7 min; S group 95% CI=11.4-18.5 min, P > or = 0.05) in both groups. TEO and ET expressed as median values (95% CI) were, respectively: 8 (6.8 to 9.2) minutes in group P versus 6 (4.6 to 7.4) in group S, P < 0.05; 10 (9.6 to 10.4) minutes in group P versus 8 (7 to 9) in group S, P < 0.05. Shivering, postoperative nausea and vomiting, pain, and seizure during the first 3 postoperative hours were not significantly different between the 2 groups, nor was BRS. Hypotension was more frequent in group S. Intraoperative diuresis and opioid consumption were greater in group P. CONCLUSIONS: Sevoflurane/remifentanil neuroanesthesia is not superior to propofol/remifentanil in time to reach an AS > or = 9. PMID- 20308818 TI - Electroacupoint stimulation for postoperative nausea and vomiting in patients undergoing supratentorial craniotomy. AB - OBJECTS: We evaluated the effectiveness of transcutaneous electrical acupoint stimulation (TEAS) at the P6 acupoint for prevention of postoperative nausea and vomiting in patients undergoing supratentorial craniotomy. METHODS: The study population was patients aged 20 to 60 years who underwent supratentorial craniotomy under general anesthesia. Exclusion criteria were obesity, diabetes mellitus, and a history of motion sickness, postoperative nausea and vomiting, or smoking. Patients were randomized into 2 groups: stimulation and control. In the former, transcutaneous stimulation electrodes were placed at the right P6 acupoint. In controls, electrodes were positioned at a nonacupoint site. Patients received a standard general anesthesia. Ondansetron was given as a routine antiemetic treatment for each patient before skin closure. Postoperatively, metoclopramide (10 mg, i.v.) was administered as a rescue antiemetic. RESULT: Forty patients received TEAS and 40 were controls. In the TEAS group, 18% of patients had nausea compared with 37% of the controls. The cumulative prevalence of vomiting was 12.5% with acustimulation and 32.5% in controls (P<0.05). The prevalence of nausea, vomiting was significantly lower with TEAS at the P6 acupoint. CONCLUSIONS: TEAS at the P6 meridian points is an effective adjunct to standard antiemetic drug therapy for prevention of nausea and vomiting in patients undergoing supratentorial craniotomy. PMID- 20308819 TI - Cerebral autoregulation and CO2 reactivity before and after elective supratentorial tumor resection. AB - BACKGROUND: The effect of surgical decompression of tumor on autoregulation and CO2 reactivity is not known. We examined the effect of elective tumor resection on cerebral autoregulation and CO2 reactivity. METHODS: Patients with supratentorial tumors undergoing elective craniotomy for tumor resection under standard anesthesia underwent cerebral autoregulation and CO2 reactivity testing immediately before and between 6 and 24 hours after surgery. Transient hyperemic response of the middle cerebral artery after the release of 10 second compression of the ipsilateral common carotid artery was used to calculate the transient hyperemic response ratio (THRR). THRR>1.1 defined the normal autoregulation. Voluntary hyperventilation was titrated to reduce the ETCO2 by 10 mm Hg below baseline and CO2 reactivity was calculated. RESULTS: Thirty-five patients (26 male and 9 female) were studied. Overall, cerebral autoregulation was intact before and after tumor resection for the cohort (THRR 1.27+/-0.10 and 1.30+/ 0.12, P=0.11). However, cerebral autoregulation was impaired preoperatively in 7 (20%) patients and remained impaired in all 7 patients after tumor resection. Larger tumor size (P=0.002), and midline shift more than 5 mm (P<0.001) were associated with impaired cerebral autoregulation. Twenty-eight (80%) patients who had intact preoperative cerebral autoregulation maintained autoregulation postoperatively. CO2 reactivity was within normal limits before and after surgery in all patients and did not change between the 2 periods (3.41+/-0.46/mm Hg and 3.60+/-0.63%/mm Hg, P=0.07). CONCLUSION: Preoperative cerebral autoregulation was impaired in a significant number of patients with large supratentorial tumor size and midline shift more than 5 mm and was associated with postoperative impaired cerebral autoregulation during the first 24 hours after the surgery. PMID- 20308820 TI - Feasibility of microdialysis to determine interstitial rocuronium concentration in the muscle tissue of anesthetized neurosurgical patients. AB - BACKGROUND: Microdialysis is used to determine the concentrations of substances in the extracellular fluid of tissues. To date, it has not been used to measure rocuronium concentrations in human muscle. We determined the ability of microdialysis to recover rocuronium from muscle interstitial tissue for the purpose of assessing the effect of chronic phenytoin therapy on muscle concentrations of rocuronium. METHODS: In a first phase, an in vitro study was performed to establish the ability of the assay to recover rocuronium. In a second phase, 17 patients undergoing brain surgery were enrolled. Eight patients were on chronic phenytoin therapy and the remaining 9 patients were not taking any antiepileptic agent (controls). Rocuronium was administered intravenously and muscle tissue samples for microdialysis were collected. RESULTS: The recovery rate of the in vitro assay was 36% at a pump rate of 1 microL/min. Rocuronium muscle tissue concentrations could be measured in 25 microdialysate samples. Rocuronium concentrations were similar in patients treated with phenytoin and in controls, although the doses required to obtain a similar effect were significantly higher in patients on chronic phenytoin treatment. CONCLUSIONS: Quantification of drug concentrations in muscle by means of microdialysis is technically feasible in the clinical setting and it might help in studying pharmacologic mechanisms of drug action. Based on our results the decrease in the degree of effect of rocuronium in the presence of chronic phenytoin therapy might seem to be due mainly to a pharmacokinetic mechanism. PMID- 20308824 TI - Adnexal masses: when to observe, when to intervene, and when to refer. PMID- 20308825 TI - Physicians influence and the malpractice problem. PMID- 20308826 TI - Predicting risk of malignancy in adnexal masses. AB - OBJECTIVE: To estimate the accuracy of preoperative ultrasonography, serum CA 125, and patient demographics as a means of predicting risk of malignancy in women with a ultrasonographically confirmed adnexal mass. METHODS: Tumor morphology derived from ultrasonographic images, tumor size, tumor bilaterality, serum CA 125, and patient demographics were evaluated preoperatively in 395 patients undergoing surgery from 2001 to 2008. Tumor morphology was classified as complex, solid, or cystic. Preoperative findings were compared with tumor histologic findings at the time of surgery. Multivariable classification and regression tree analysis were used to identify a group of patients at high risk of ovarian malignancy. RESULTS: One hundred eighteen patients had ovarian cancer, 13 patients had ovarian tumors of borderline malignancy, and 264 had benign ovarian tumors. Multivariable classification and regression tree analysis defined women at high risk of ovarian malignancy as those with an adnexal mass having complex or solid morphology and a serum CA 125 value greater than 35 units/mL. This definition had a positive predictive value of 84.7% and a negative predictive value of 92.4% and correctly identified 77.3% of patients with stage I and stage II ovarian cancer and 98.6% of patients with stage III and stage IV ovarian cancer. CONCLUSION: Patients with solid or complex ovarian tumors and an elevated serum CA 125 level (greater than 35 units/mL) are at high risk of ovarian malignancy. LEVEL OF EVIDENCE: II. PMID- 20308827 TI - Neutrophil count for the identification of postmenopausal hypertensive women at increased cardiovascular risk. AB - OBJECTIVE: High white blood cell and neutrophil counts identify patients at increased cardiovascular risk in various clinical settings. However, the prognostic value of white blood cell and neutrophil counts in hypertensive postmenopausal women is unknown. We tested the independent prognostic value of total white blood cell and neutrophil counts for cardiovascular events in hypertensive postmenopausal women. METHODS: We examined 298 initially untreated postmenopausal women with essential hypertension who were part of Progetto Ipertensione Umbria Monitoraggio Ambulatoriale (PIUMA). Mean duration of follow up was 8 years (range 1-20 years). Treatment was tailored to each individual. RESULTS: Mean age at entry was 59 years. Diabetic women comprised 9.1% of the group, and current smokers comprised 17.5% of the group. During follow-up, 31 new major cardiovascular events occurred. In univariable analyses, age, diabetes, serum creatinine, blood pressure, left ventricular hypertrophy, and neutrophil count showed an association with the risk of events (all P<.05). In a multivariable Cox analysis, after adjustment for traditional cardiovascular risk factors, for each 1.25x10 (1 standard deviation) increase in neutrophil count there was a 67% higher risk of cardiovascular events (hazard ratio 1.67, 95% confidence interval 1.32-2.07; P<.001). Furthermore, neutrophil count showed robust incremental predictive value for cardiovascular events, in addition to traditional risk factors. Total white blood cell count did not show any association with cardiovascular events. CONCLUSION: A high peripheral neutrophil count identifies postmenopausal hypertensive women at increased risk of cardiovascular disease. Such relation appears to be independent of traditional risk factors. LEVEL OF EVIDENCE: III. PMID- 20308828 TI - The natural history of the normal first stage of labor. AB - OBJECTIVE: To examine labor patterns in a large population and to explore an alternative approach for diagnosing abnormal labor progression. METHODS: Data from the National Collaborative Perinatal Project were used. A total of 26,838 parturients were selected who had a singleton term gestation, spontaneous onset of labor, vertex presentation, and a normal perinatal outcome. A repeated measures analysis was used to construct average labor curves by parity. An interval-censored regression was used to estimate duration of labor stratified by cervical dilation at admission and centimeter by centimeter. RESULTS: The median time needed to progress from one centimeter to the next became shorter as labor advanced (eg, from 1.2 hours at 3-4 cm to 0.4 hours at 7-8 cm in nulliparas). Nulliparous women had the longest and most gradual labor curve; multiparous women of different parities had very similar curves. Nulliparas may start the active phase after 5 cm of cervical dilation and may not necessarily have a clear active phase characterized by precipitous dilation. The deceleration phase in the late active phase of labor may be an artifact in many cases. CONCLUSION: The active phase of labor may not start until 5 cm of cervical dilation in multiparas and even later in nulliparas. A 2-hour threshold for diagnosing labor arrest may be too short before 6 cm of dilation, whereas a 4-hour limit may be too long after 6 cm. Given that cervical dilation accelerates as labor advances, a graduated approach based on levels of cervical dilation to diagnose labor protraction and arrest is proposed. LEVEL OF EVIDENCE: III. PMID- 20308829 TI - Maternal and neonatal outcomes after antepartum treatment of influenza with antiviral medications. AB - OBJECTIVE: To review the maternal and neonatal outcomes after antepartum exposure to M2 ion channel inhibitors or oseltamivir to provide some guidance on the risk, if any, of antiviral medication during pregnancy. METHODS: This was a retrospective cohort study examining maternal and neonatal outcomes after antepartum exposure to antiviral therapy for influenza. We evaluated maternal characteristics, pregnancy outcomes, and fetal outcomes and compared them with our overall obstetric population. RESULTS: Exposure to antiviral therapies (M2 ion channel inhibitors [n=104] compared with oseltamivir [n=135] compared with the control group [n=82,097]) during pregnancy was not associated with increased rates of preterm birth (7% compared with 10% compared with 6%, P=.190), premature rupture of membranes (23% compared with 16% compared with 22%, P=.154), gestational diabetes (4% compared with 8% compared with 6%, P=.388), or preeclampsia (6% compared with 1% compared with 4%, P=.209). Exposure was not associated with increased duration of hospital stay for mother or neonate. There were no differences in the incidence of minor malformations (19% compared with 15% compared with 22%, P=.101). Liveborn singletons without major malformations did not have differences in fetal weight (3,238+/-586 g compared with 3,281+/-642 g compared with 3,336+/-571 g, P=.186), need for intubation (2% compared with 0.8% compared with 1%, P=.552), intensive care nursery admission (3% compared with 3% compared with 2%, P=.418), or hyperbilirubinemia (12% compared with 9% compared with 8%, P=.282). Liveborn singletons had no grade 3 or 4 intraventricular hemorrhages, seizures, or neonatal deaths. Two preterm neonates exposed to different classes of medications had necrotizing enterocolitis (1.0% compared with 0.8% compared with 0.02%, P<.001). CONCLUSION: We found no evidence of an association between antepartum antiviral exposure and adverse outcomes. LEVEL OF EVIDENCE: II. PMID- 20308830 TI - Severity of 2009 pandemic influenza A (H1N1) virus infection in pregnant women. AB - OBJECTIVE: To examine 2009 H1N1 influenza illness severity and the effect of antiviral treatment on the severity of illness among pregnant women. METHODS: We abstracted medical records from hospitalized pregnant (n=62) and nonpregnant (n=74) women with laboratory-confirmed 2009 H1N1 influenza in New York City, May through June 2009. We compared characteristics of pregnant and nonpregnant women and of severe and moderate influenza illness among pregnant women, with severe defined as illness resulting in intensive care admission or death. RESULTS: The 2009 H1N1 hospitalization rate was significantly higher among pregnant than nonpregnant women (55.3 compared with 7.7 per 100,000 population). Eight pregnant (including two deaths) and 16 nonpregnant (including four deaths) cases were severe. Pregnant women represented 6.4% of hospitalized cases and 4.3% of deaths caused by 2009 H1N1 influenza. Only 1 in 30 (3.3%) pregnant women who received oseltamivir treatment within 2 days of symptom onset had severe illness compared with 3 of 14 (21.4%) and four of nine (44.4%) pregnant women who started treatment 3-4 days and 5 days or more after symptom onset, respectively (P=.002 for trend). Severe and moderate 2009 H1N1 influenza illness occurred in all pregnancy trimesters, but most women (54.8%) were in the third trimester. Twenty two women delivered during their influenza hospitalization, and severe neonatal outcomes (neonatal intensive care unit admission or death) occurred among five of six (83.3%) women with severe illness compared with 2 of 16 (12.5%) women with moderate illness (P=.004). CONCLUSION: Our findings highlight the potential for severe illness and adverse neonatal outcomes among pregnant 2009 H1N1 influenza infected women and suggest the benefit of early oseltamivir treatment. LEVEL OF EVIDENCE: II. PMID- 20308831 TI - Accuracy of real-time polymerase chain reaction for Toxoplasma gondii in amniotic fluid. AB - OBJECTIVE: To provide clinicians with information about the accuracy of real-time polymerase chain reaction (PCR) analysis of amniotic fluid for the prenatal diagnosis of congenital Toxoplasma infection. METHODS: This was a prospective cohort study of women with Toxoplasma infection identified by prenatal screening in three centers routinely carrying out real-time PCR for the detection of Toxoplasma gondii in amniotic fluid. The data available were gestational age at maternal infection, types and dates of maternal treatment, results of amniocentesis and neonatal work-up and definitive infectious status of the child. We estimated sensitivity, specificity and positive and negative predictive values both overall and per trimester of pregnancy at the time of maternal infection. RESULTS: Polymerase chain reaction analysis was carried out on amniotic fluid for 261 of the 377 patients included (69%). It was accurate with the exception of four negative results in children who were infected. Overall sensitivity and negative predictive value were 92.2% (95% confidence interval [CI] 81-98%) and 98.1% (95% CI 95-99.5%), respectively. There was no significant association with the trimester of pregnancy during which maternal infection occurred. Specificity and positive predictive values of 100% were obtained for all trimesters. CONCLUSION: Real-time PCR analysis significantly improves the detection of T. gondii on amniotic fluid. It provides an accurate tool to predict fetal infection and to decide on appropriate treatment and surveillance. However, postnatal follow-up remains necessary in the first year of life to fully exclude infection in children for whom PCR results were negative. LEVEL OF EVIDENCE: III. PMID- 20308832 TI - Association between tampon use and choosing the contraceptive vaginal ring. AB - OBJECTIVE: To estimate whether tampon users are more likely to select the contraceptive vaginal ring than combined oral contraceptive pills (OCPs). METHODS: The Contraceptive Choice Project is a longitudinal study of 10,000 St. Louis area women promoting the use of long-acting, reversible methods of contraception and evaluating user continuation and satisfaction for all reversible methods. We performed univariable and multivariable analyses of the 311 women who were asked about tampon use at the time of enrollment and who chose the contraceptive vaginal ring or OCPs to assess the association of tampon use and choice of combined hormonal method. RESULTS: Among contraceptive vaginal ring and OCP users, 247 (79%) reported using tampons. Contraceptive vaginal ring users were not significantly different from OCP users in terms of age, race or ethnicity, marital status, insurance, body mass index, or parity. Adjusted analysis indicated that tampon users were more likely to choose the contraceptive vaginal ring instead of OCPs (adjusted relative risk 1.34, 95% confidence interval 1.01-1.78). Women with previous contraceptive vaginal ring experience were also more likely to choose the contraceptive vaginal ring (adjusted relative risk 1.96, 95% confidence interval 1.6-2.4). Recent OCP use did not influence method choice. CONCLUSION: In our baseline analysis of the Contraceptive Choice Project, tampon users were more likely to choose the contraceptive vaginal ring than OCPs. Use of tampons could be considered an indicator for the initial acceptability of the contraceptive vaginal ring, but all women should be offered the contraceptive vaginal ring regardless of experience with tampon use. LEVEL OF EVIDENCE: II. PMID- 20308833 TI - Gestrinone compared with mifepristone for emergency contraception: a randomized controlled trial. AB - OBJECTIVE: To compare the efficacy of gestrinone with that of mifepristone for emergency contraception. METHODS: A randomized double-blind trial was conducted in five family-planning clinics in China. We randomly assigned 998 healthy women with regular menstrual cycles and negative urine pregnancy tests who were requesting emergency contraception up to 72 hours after unprotected coitus to receive single-dose 10 mg gestrinone (n=499) or 10 mg mifepristone (n=499). We monitored them to 7 days after the expected first day of their next menstrual period. The study was powered to detect a 5% failure rate between the two regimens. RESULTS: The treatment groups did not differ significantly; posttreatment pregnancy rates were 2.4% in the gestrinone group compared with 1.8% in the mifepristone group (P=.51). The majority of women menstruated the first day of expected menses, and groups did not differ regarding side effects. CONCLUSION: The effectiveness of 10 mg gestrinone is not significantly different from 10 mg mifepristone as an emergency contraceptive method. CLINICAL TRIAL REGISTRATION: ISRCTN Register, isrctn.org, ISRCTN87842530. LEVEL OF EVIDENCE: I. PMID- 20308834 TI - Home screening compared with clinic-based screening for sexually transmitted infections. AB - OBJECTIVE: To estimate completion rate and acceptability of home screening for sexually transmitted infections (STIs) compared with clinic-based screening in a prospective cohort study. METHODS: The first 462 women enrolled in the Contraceptive Choice Project were screened at the 12-month follow-up for Chlamydia trachomatis and Neisseria gonorrhoeae using strand displacement analysis of self-collected vaginal swabs. In a telephone interview, participants were given a choice of no-cost screening with swabs mailed to the participant's home (home-based) or screening that was available at area family planning clinics without an appointment (clinic-based). The clinic-based group also included women who elected to screen with their regular provider according to the clinician's normal practice. We analyzed the rates of screening, including patient preference and the proportion of completed tests by testing method. RESULTS: Women were more likely to choose to screen for STIs at home than at a clinic or with their own medical provider (75.7% compared with 16.1% compared with 8.2%, P<.001). Women choosing clinic testing were more likely to be African American than those choosing home testing. African-American women constituted 42% of the clinic group compared with 28% of the home group (relative risk [RR] 1.63, 95% confidence interval [CI] 1.14-2.31). The groups did not differ in other demographic characteristics, STI risk factors, or access to health care. Overall, 228 women (56.6%) completed screening. Women who chose home-based testing were more likely to complete a test compared with all clinic-based testers (64.6% compared with 31.6%, RR 2.04, 95% CI 1.51-2.76). CONCLUSION: Women overwhelmingly preferred to screen for STIs at home. Future interventions to increase screening rates in young women should consider alternative screening strategies such as home-based or patient-controlled testing. LEVEL OF EVIDENCE: II. PMID- 20308835 TI - Results of a program to test women for rectal chlamydia and gonorrhea. AB - OBJECTIVE: To analyze whether rectal testing among women increased chlamydia and gonorrhea case-finding and whether reported receptive anal intercourse was a risk factor for rectal infection. METHODS: From March 2007 to August 2008, women receiving pelvic examinations at the San Francisco sexually transmitted disease clinic were tested for rectal gonorrhea and chlamydia by using a transcription mediated amplification assay. Results of testing and clinical and demographic data were analyzed using a cross-sectional study design. RESULTS: Of 1,308 women with both rectal and vaginal tests, test results were positive for 79 patients (6.0%) for rectal chlamydia or gonorrhea and 88 patients (6.7%) for genital chlamydia or gonorrhea. Test results were positive for 13 patients (1.0%) at the rectum only, increasing detection from 88 to 101 patients (14.8%; 95% confidence interval 8.1-23.9). No correlation existed between reported anal sex and rectal chlamydia (P=.74); however, 50% of women with rectal gonorrhea reported anal sex compared with 21% of women without rectal gonorrhea (P=.002). CONCLUSION: Sexually transmitted disease clinics might improve chlamydia and gonorrhea case finding through rectal testing of women, but more study is needed to determine the effects of finding and treating such infections. Reporting anal intercourse did not predict rectal chlamydial infection among women tested at both the rectum and the vagina. LEVEL OF EVIDENCE: II. PMID- 20308836 TI - Effect of prior cesarean delivery on risk of second-trimester surgical abortion complications. AB - OBJECTIVE: To estimate second-trimester surgical abortion complication rates and to estimate the effect of past cesarean delivery on the risk of complications. METHODS: Demographic, medical, and operative data were collected prospectively between October 2004 and March 2007 in an academic, urban, U.S. abortion clinic. Complication and intervention rates were calculated. Multivariable logistic regression models were used to evaluate risk factors for a major complication, hemorrhage, cervical laceration, and atony. RESULTS: We included 2,973 second trimester surgical abortions. Cervical laceration (3.3%), atony (2.6%), and hemorrhage (1.0%) were the most common complications. The rate of major complications (eg, transfusion, disseminated intravascular coagulation, and reoperation) was 1.3%. In multivariable logistic regression modeling, a history of two or more cesarean deliveries was the strongest predictor for having a major complication (odds ratio [OR] 7.4, 95% confidence interval [CI] 3.4-15.8), while additional predictors included gestational age of 20 weeks or more (OR 4.4, 95% CI 2.0-11.4) and insufficient initial cervical preparation requiring further dilation (OR 2.6, 95% CI 1.2-5.4). CONCLUSION: Second-trimester surgical abortions were associated with a major complication rate of approximately 1%. A history of two or more cesarean deliveries was associated with a sevenfold increase in odds of major complication and was the strongest independent risk factor for a major complication. LEVEL OF EVIDENCE: III. PMID- 20308837 TI - Progesterone receptor genotype, family history, and spontaneous preterm birth. AB - OBJECTIVE: To examine whether women with a personal or family history of preterm birth are more likely to have genetic variation in the human progesterone receptor (hPR). METHODS: Women with a singleton preterm birth at less than 37 weeks of gestation between 2002 and 2006 were identified from a prospectively collected clinical and biologic obstetric database (cases). Women in the control group were those with only term deliveries at or above 38 weeks of gestation. The Utah Population Database was queried for family history (first- or second-degree relative) of preterm birth. DNA was extracted from stored buffy coats and genotyped for six single nucleotide polymorphisms in the hPR. RESULTS: One hundred fifty-four patients (92 women in the preterm case group, 62 women in the term control group) were included. All were white or Hispanic. There were no statistical differences between white and Hispanic allele frequencies. Women in the preterm case group were more likely to carry the minor allele, G (minor allele frequency 0.29 compared with 0.18, P=.035) for rs471767, and were more likely to carry the GT haplotype across rs471767 and rs578029 compared with women in the term control group. Similar haplotype block variation was seen among women with preterm birth plus a family history of preterm birth. CONCLUSION: Allele and haplotype frequencies in the hPR are significantly different among women with preterm birth and women with preterm birth plus a family history of preterm birth. This suggests the hPR gene may be a candidate for association with preterm birth or familial preterm birth. LEVEL OF EVIDENCE: III. PMID- 20308838 TI - Chorioamnion separation as a risk for preterm premature rupture of membranes after laser therapy for twin-twin transfusion syndrome. AB - OBJECTIVE: To compare the outcomes in chorioamnion membrane separation with nonchorioamnion membrane separation cases after fetoscopic laser photocoagulation of placental anastomoses for the treatment of twin to twin transfusion syndrome. METHODS: We performed a retrospective cohort study of twin to twin transfusion syndrome cases that underwent laser ablation at the Texas Children's Fetal Center from October 2007 to March 2009. The cases were identified from our database. We excluded triplet pregnancies. Chorioamnion membrane separation was identified by ultrasound examination performed within 24 hours of intervention. Preterm premature rupture of membranes (PROM) was defined as rupture of the membranes before 34 weeks of gestation. RESULTS: Ninety-seven cases were included in the analysis; 19 (19.6%) had chorioamnion membrane separation. There were no significant differences in preoperative and intraoperative variables, except for a lower recipient maximum vertical pocket (10.3+/-2.1 compared with 12.6+/-3.4; P<.01), and higher rate of iatrogenic septostomy (21% compared with 2.5%; P=.01) in the chorioamnion membrane separation group. Postoperatively, the incidence of preterm PROM was 74% in chorioamnion membrane separation group compared with 23% in the nonchorioamnion membrane separation group (relative risk 3.2, 95% confidence interval 1.9-4.4). The procedure-to-delivery interval was reduced by 20 days in the chorioamnion membrane separation group (P<.01). The neonatal survival rate was 63.2% in the chorioamnion membrane separation group compared with 84% in the nonchorioamnion membrane separation group (P=.016). CONCLUSION: A low preoperative recipient maximum vertical pocket is associated with increased risk of chorioamnion membrane separation. Postoperative chorioamnion membrane separation after laser surgery for twin to twin transfusion syndrome is a major risk factor for preterm PROM, early delivery, and an increase in perinatal mortality. LEVEL OF EVIDENCE: II. PMID- 20308839 TI - Efforts needed to provide Institute of Medicine-recommended guidelines for gestational weight gain. AB - OBJECTIVE: To estimate body mass index (BMI)-specific gestational weight gain recommendations and frequency of weight and gestational weight gain discussions and documentation. METHODS: Medical record review of 477 randomly selected patients who met inclusion criteria and who received care in faculty and resident clinics at a central Massachusetts tertiary care center. Patients started prenatal care at or before 14 weeks of gestation and delivered between April 2007 and March 2008. RESULTS: Our patients were mean (+/-standard deviation) 27.8 (+/ 6.3) years, 69.8% multiparous, 45.3% white, 10.5% black, and 15.9% Hispanic. Mean gestational age at initial visit was 9.6 (+/-2.1) weeks and mean prenatal visits attended were 12.6 (+/-2.7). Using prenatal chart data alone, BMI was not calculable for 41.2% of patients due to missing height (27.7%), prepregnancy weight (27.9%), or both (14.5%). In the total sample, documentation was missing with regard to BMI (95.4%), gestational weight gain (85.3%), gestational weight gain goals (90.1%), and discussion of weight (88.9%). Supplemental data were obtained to calculate prepregnancy BMI for 469 patients. Per 1990 (BMI at least 26.1) and 2009 (BMI at least 25.0) guidelines, 42% and 49% of patients were overweight or obese, respectively, before pregnancy. Analysis of actual gestational weight gain by BMI revealed that 76% of overweight and 65% of obese patients gained excessively. CONCLUSION: Prenatal care providers should include recording height and weight to calculate BMI and to provide BMI-specific gestational weight gain guidelines. LEVEL OF EVIDENCE: III. PMID- 20308840 TI - Precise DNA genotyping diagnosis of hydatidiform mole. AB - OBJECTIVE: To estimate whether tissue DNA genotyping is effective for the confirmation and subclassification of hydatidiform moles. METHODS: Consecutive cases of products of conception were selected based on histologic alterations that are suspicious for molar pregnancy. DNA genotyping was performed by a multiplex polymerase chain reaction targeting 15 tetrameric polymorphic loci of the human genome. RESULTS: A total of 205 products of conception were included. DNA genotyping was informative in all, leading to the final identification of 60 cases of hydatidiform moles, including 17 complete and 43 partial moles. Among 17 cases of complete moles, 14 cases were monospermic and three were dispermic. Forty-three cases were confirmed as triploid partial moles, 42 of which were dispermic and one was monospermic. Among nonmolar cases, 32 gestations showed allelic changes indicating chromosomal alterations, including 28 cases of trisomy syndrome: trisomy 16 (eight cases), trisomy 21 (six cases), trisomy 7 (three cases), trisomy 13 (three cases), trisomy 4 (one case), trisomy 8 (one case), trisomy 18 (one case), XXY/Klinefelter syndrome (one case), and multiple trisomies (four cases). Monosomy 22 was seen in one case. Two nonmolar cases were triploid digynic-monoandric gestations. More complex chromosomal abnormalities were seen in one case. The remaining 113 cases were balanced biallelic gestations. CONCLUSION: Tissue DNA genotyping is a practical and highly accurate method for the confirmation and subclassification of hydatidiform moles. LEVEL OF EVIDENCE: III. PMID- 20308841 TI - Vitamin D and pelvic floor disorders in women: results from the National Health and Nutrition Examination Survey. AB - OBJECTIVE: To estimate the prevalence of vitamin D deficiency in women with pelvic floor disorders and to evaluate possible associations between vitamin D levels and pelvic floor disorders. METHODS: Using 2005-2006 National Health and Nutrition Examination Survey data, we performed a cross-sectional analysis of nonpregnant women older than 20 years of age with data on both pelvic floor disorders and vitamin D measurements (n=1,881). Vitamin D levels lower than 30 ng/mL were considered insufficient. The prevalence of demographic factors, pelvic floor disorders, and vitamin D levels were determined, accounting for the multi stage sampling design; odds ratios (OR) and 95% confidence intervals (CI) were calculated to evaluate associations between vitamin D levels and pelvic floor disorders with control for known risk factors. RESULTS: One or more pelvic floor disorders were reported by 23% of women. Mean vitamin D levels were significantly lower for women reporting at least one pelvic floor disorder and for those with urinary incontinence, irrespective of age. In adjusted logistic regression models, we observed significantly decreased risks of one or more pelvic floor disorders with increasing vitamin D levels in all women aged 20 or older (OR, 0.94; 95% CI, 0.88-0.99) and in the subset of women 50 years and older (OR, 0.92; 95% CI, 0.85-0.99). Additionally, the likelihood of urinary incontinence was significantly reduced in women 50 and older with vitamin D levels 30 ng/mL or higher (OR, 0.55; 95% CI, 0.34-0.91). CONCLUSION: Higher vitamin D levels are associated with a decreased risk of pelvic floor disorders in women. LEVEL OF EVIDENCE: III. PMID- 20308842 TI - The influence of pelvic muscle activation during vaginal delivery. AB - OBJECTIVE: To estimate the influence of pelvic floor muscle activation during vaginal delivery using a three-dimensional computational finite element model. METHODS: A computational finite element model of the pelvic skeletal structure, pelvic floor, and fetus was developed. The movements of the fetus during birth, in vertex position, were simulated; namely, the engagement, descent, flexion, internal rotation, and extension of the fetal head. The opposite forces against the fetal descent and the stress on the pelvic floor muscles were obtained in passive, 5%, 10%, and 15% pelvic floor muscle simulated activations. RESULTS: The increase in pelvic floor muscle activation was associated with higher values of forces against the fetal descent. The descending fetus encountered increasing resistance in higher stations with the increase in pelvic floor muscle activation. The maximum values of stress of the pelvic floor muscles were obtained in +4 station. The increase in pelvic floor muscle activation was also followed by higher values of pelvic floor stress. CONCLUSION: This study demonstrates the feasibility of using a computational modeling approach to study parturition. This experimental evidence suggests that the pelvic floor muscle activation during vaginal delivery may represent an obstacle to fetal descent and increase the risk for pelvic floor injuries. LEVEL OF EVIDENCE: III. PMID- 20308843 TI - Quality of life in women with postpartum anal incontinence. AB - OBJECTIVE: To estimate the effect of anal incontinence on postpartum quality of life (QOL). METHODS: We conducted a longitudinal follow-up study of women reporting anal incontinence on a statewide postpartum survey to estimate the effect of anal incontinence on QOL up to 2 years postpartum. Quality of life was assessed every 6 months for 2 years based on the Uebersax incontinence impact questionnaire. The effect of severe anal incontinence on QOL was determined by multivariate logistic regression. RESULTS: A total of 1,050 women reported persistent anal incontinence and returned at least two completed QOL surveys during the 2-year study period. Among women with anal incontinence, 51% reported frustration caused by anal incontinence, 26% reported that anal incontinence affected their emotional health, 18.5% reported anal incontinence affected their child-caring abilities, and 16.2% reported a negative effect on social activities. One in three women with anal incontinence reported severe symptoms. Compared with women with mild anal incontinence, women with severe anal incontinence were four to seven times as likely to report that anal incontinence affected emotional health and the ability to perform daily activities. However, only 10% of women sought medical help for anal incontinence at 6 months, 13.5% at 1 year, and 16.7% at 2 years. CONCLUSION: Even 2 years after delivery, more than a quarter of women who experience a new onset of anal incontinence after childbirth report persistently negative QOL. Despite this, few women discuss anal incontinence with their medical providers. LEVEL OF EVIDENCE: III. PMID- 20308844 TI - Effect of myogenic stem cells on contractile properties of the repaired and unrepaired transected external anal sphincter in an animal model. AB - OBJECTIVE: To estimate the effect of myogenic stem cells on contractile function of the external anal sphincter after transection with or without repair in an animal model. METHODS: One hundred twenty virginal female rats were randomly assigned to repair (n=60) or no repair (n=60) after anal sphincter transection. Animals were further divided into two groups: 40-microliter injection at the transection site with either phosphate-buffered solution (control) or myogenic stem cells (3.2x10 cells). Animals were killed at 7, 21, or 90 days, and the anal sphincter complex dissected and analyzed for contractile function. RESULTS: Contractile function of the external anal sphincter was severely impaired 7 days after sphincter transection with or without repair. Twitch tension, maximal tetanic contraction, and maximal contractile force in response to electrical field stimulation improved significantly with time after sphincter repair. Injection of myogenic stem cells in the anal sphincter at the time of repair resulted in superior contractile function at both 7 days and 90 days compared with controls. Interestingly, contractile function of the nonrepaired external anal sphincter did not improve with time with or without myogenic stem cells. Indicators of denervation (fatigue and twitch or tetany ratios) did not change among groups. CONCLUSION: In this animal model, injection of myogenic stem cells at the time of external anal sphincter repair resulted in enhanced contractile function at 90 days compared with repair alone. Without repair, function of the external anal sphincter was not improved by stem cell therapy at any time point. These results suggest that addition of myogenic stem cells improves both acute and long-term function of the external anal sphincter after mechanical injury. PMID- 20308845 TI - U.S. Food and Drug Administration drug approval: slow advances in obstetric care in the United States. AB - The process for drug approval in the United States is complex and time-consuming. There are comparatively few drugs with U.S. Food and Drug Administration (FDA) approved indications for obstetric use in this country at this time; however, several are under development. We review the process for drug approval and recount the approval histories of obstetric drugs reviewed in the recent past. We also outline the current status of two progestational agents that are under development. For a variety of reasons, including a small market compared with others such as cardiology or oncology, and the potential of being drawn into medical-legal litigation, sponsors are disinclined to pursue drug development for obstetric purposes in this country. We compare the procedures for review and approval of drugs in the United States with those in Europe, and note that recent changes within the FDA may result in not only more drugs being approved but also changes in labeling of already approved drugs. Special programs to facilitate drug development and reforms to modernize the process and improve safety are discussed. These may result in changes in labeling of already approved drugs. Obstacles such as funding and liability are also discussed. PMID- 20308846 TI - Cervical cancer prevention through human papillomavirus vaccination: using the "teachable moment" for educational interventions. AB - Cervical cancer represents a global women's health issue. The emergence of vaccines against the most common types of human papillomaviruses causing cervical cancer represents a significant advance in cervical cancer prevention. Adolescent girls are the primary target population for vaccination-a population that traditionally has been difficult to reach. Obstetricians and gynecologists may hold the key to improving adolescent human papillomavirus vaccinations through the novel use of their existing relationships with adolescents' mothers during the routine cervical cancer screening visit. We propose using maternal cancer screenings, specifically breast and cervical cancer screening episodes, as "teachable moments," naturally occurring life or health events thought to motivate a person to adopt risk-reducing health behaviors spontaneously, to improve human papillomavirus vaccination rates among adolescents. PMID- 20308847 TI - Role of hormone therapy in the management of menopause. AB - There are many options available to address the quality of life and health concerns of menopausal women. The principal indication for hormone therapy (HT) is the treatment of vasomotor symptoms, and benefits generally outweigh risks for healthy women with bothersome symptoms who elect HT at the time of menopause. Although HT increases the risk of coronary heart disease, recent analyses confirm that this increased risk occurs principally in older women and those a number of years beyond menopause. These findings do not support a role for HT in the prevention of heart disease but provide reassurance regarding the safety of use for hot flushes and night sweats in otherwise healthy women at the menopausal transition. An increased risk of breast cancer with extended use is another reason short-term treatment is advised. Hormone therapy prevents and treats osteoporosis but is rarely used solely for this indication. If only vaginal symptoms are present, low-dose local estrogen therapy is preferred. Contraindications to HT use include breast or endometrial cancer, cardiovascular disease, thromboembolic disorders, and active liver disease. Alternatives to HT should be advised for women with or at increased risk for these disorders. The lowest effective estrogen dose should be provided for the shortest duration necessary because risks increase with increasing age, time since menopause, and duration of use. Women must be informed of the potential benefits and risks of all therapeutic options, and care should be individualized, based on a woman's medical history, needs, and preferences. PMID- 20308848 TI - Fertility and uterine artery embolization. PMID- 20308849 TI - Urgent cesarean delivery for fetal bradycardia. PMID- 20308851 TI - Cycle control with a 21-day compared with a 24-day oral contraceptive pill: a randomized controlled trial. PMID- 20308853 TI - Fetal monitoring bundle. PMID- 20308855 TI - Cycle control with a 21-day compared with a 24-day oral contraceptive pill: a randomized controlled trial. PMID- 20308857 TI - Pregnancy and laboratory studies: a reference table for clinicians. PMID- 20308858 TI - Vesico-uterine fistula after endometrial ablation in a woman with prior cesarean deliveries. PMID- 20308860 TI - ACOG Practice Bulletin No. 111: Inherited thrombophilias in pregnancy. AB - Inherited thrombophilias are associated with an increased risk of venous thromboembolism and also have been linked to adverse outcomes in pregnancy. However, there is limited evidence to guide screening for and management of these conditions in pregnancy. The purpose of this document is to review common thrombophilias and their association with maternal venous thromboembolism risk and adverse pregnancy outcomes, indications for screening to detect these conditions, and management options in pregnancy. PMID- 20308863 TI - Factors affecting graft and patient survival after live donor kidney transplantation in the UK. AB - BACKGROUND: The outcome after living donor renal transplantation is superior to that for deceased donor transplantation, but the results are not uniformly successful. The factors responsible for the variable outcome after living donor transplantation have not been well defined. METHODS: UK Transplant Registry data were analyzed to determine the outcomes of 3142 first adult kidney transplants from living donors (71% genetically related and 29% unrelated) performed between 2000 and 2007 inclusive. Kaplan-Meier survival estimates were determined, and factors that might be associated with graft and patient survival were analyzed using Cox proportional hazards regression modeling. RESULTS: Patient survival at 5 years was better for recipients of grafts from related than unrelated donors (97% vs. 93%, P=0.0002), but conversely graft survival was better in recipients of genetically unrelated grafts (93% vs. 89%, P=0.06). After adjustment for the factors found to influence graft and patient survival, these differences were no longer apparent. In contrast to the expectations, the degree of human leukocyte antigen-A, -B, and -DR mismatch did not influence graft survival. Increasing donor age (but not recipient age), recipient diabetes, and grafts from adult offspring were independently associated with poorer patient survival in the first 3 years after transplantation. Poorer graft survival was independently associated with donor age older than 59 years, and female recipients. CONCLUSIONS: Advanced donor age, but not human leukocyte antigen mismatch, is associated with poorer outcome after live donor kidney transplantation. However, the results of live donor transplantation remain superior to deceased donor kidney transplantation. PMID- 20308864 TI - A new role for the virtual crossmatch in kidney allograft reuse. PMID- 20308865 TI - Back-table thrombolysis in live donor kidney transplantation. PMID- 20308866 TI - The use of explanted internal iliac artery grafts in renal transplants with multiple arteries. PMID- 20308867 TI - Early relapse of autoimmune glomerulonephritis after kidney transplantation despite antibody induction and triple-drug-based immunosuppression. PMID- 20308868 TI - Experiences in uterine transplantation. PMID- 20308869 TI - Clinical outcomes of sorafenib treatment in patients with metastatic hepatocellular carcinoma who had been previously treated with fluoropyrimidine plus platinum-based chemotherapy. AB - OBJECTIVES: There has been no report on sorafenib therapy in patients with metastatic hepatocellular carcinoma (HCC) who had been treated with systemic chemotherapy. The objectives of this analysis were to investigate efficacy and safety of sorafenib in these patients and to elucidate risk factors associated with clinical outcomes. METHODS: We analyzed patients with metastatic HCC who were treated with sorafenib after failure of fluoropyrimidine plus platinum-based chemotherapy between April 2007 and December 2008. RESULTS: Twenty-four patients (male, 79.2%) were included. Median age was 53 years. Chronic hepatitis B was the predominant cause of HCC (79.2%), followed by chronic hepatitis C (4.2%) and alcohol (4.2%). Twenty patients (83.3%) were Child-Pugh A and 4 patients (16.7%) were Child-Pugh B. Median follow-up duration was 11.1 months. No objective response was observed. Fourteen patients (58.3%) had stable disease. The disease control rate was 58.3%. Median progression-free survival was 2.3 months (95% confidence interval, 0.5-4.1) and overall survival was 7.1 months (95% confidence interval, 3.5-10.7). Grade 3 neutropenia was observed in 1.4% and grade 3 anemia in 1.4%. Grade 3 or 4 nonhematologic toxicities were hand-foot syndrome (16.7%), skin rash (8.3%), diarrhea (4.2%), headache (4.2%), and fatigue (4.2%). Four patients (16.7%) discontinued the therapy because of toxicities. CONCLUSIONS: Sorafenib had modest efficacy and tolerable toxicity in patients with metastatic HCC who had received fluoropyrimidine plus platinum-based chemotherapy. PMID- 20308870 TI - Stereotactic body radiotherapy in the treatment of advanced adenocarcinoma of the pancreas. AB - OBJECTIVES: The aim of the study was to assess the feasibility and safety of stereotactic body radiotherapy (SBRT) in patients with advanced pancreatic adenocarcinoma. METHODS: We reviewed outcomes of 71 patients treated with SBRT for pancreatic cancer between July 2004 and January 2009. Forty patients (56%) had locally unresectable disease, 11 patients (16%) had local recurrence following surgical resection, 8 patients (11%) had metastatic disease, and 12 patients (17%) received adjuvant SBRT for positive margins. The median dose was 24 Gy (18-25 Gy), given in a single-fraction SBRT (n = 67) or fractionated SBRT (n = 4). Kaplan-Meyer survival analyses were used to estimate freedom from local progression (FFLP) and overall survival (OS) rates. RESULTS: The median follow-up among surviving patients was 12.7 months (4-26 months). The median tumor volume was 17 mL (5.1-249 mL). The overall FFLP rates at 6 months/1 year were 71.7%/48.5%, respectively. Among those with macroscopic disease, FFLP was achieved in 77.3% of patients with tumor size <15 mL (n = 22), and 59.5% for >=15 mL (n = 37) (P = 0.02). FFLP was achieved in 73% following 24 to 25 Gy, and 45% with 18 to 22 Gy (P = 0.004). The median OS was 10.3 months, with 6 month/1 year OS rates of 65.3%/41%, respectively. Grade 1-2 acute and late GI toxicity were seen in 39.5% of patients. Three patients experienced acute grade 3 toxicities. CONCLUSIONS: SBRT is feasible, with minimal grade >=3 toxicity. The overall FFLP rate for all patients was 64.8%, comparable to rates with external beam radiotherapy. This shorter treatment course can be delivered without delay in adjuvant systemic therapy. PMID- 20308871 TI - Overrepresentation of males in traumatic brain injury of infancy and in infants with macrocephaly: further evidence that questions the existence of shaken baby syndrome. AB - Shaken baby syndrome (SBS) has been thought to be caused by violent shaking of an infant and is characterized by the triad of findings: subdural hematoma (SDH), retinal hemorrhages, and neurologic abnormalities. The triad is not specific for SBS and can be seen in accidental trauma and in certain medical conditions. Recent observations, however, question whether SBS exists. Herein, we review the gender differences in 3 groups of infants with traumatic brain injury: (1) neonates with SDH from birth trauma, (2) infants with SDH from accidental trauma, and (3) infants with SDH from SBS. Gender differences are also presented in a fourth group of infants with macrocephaly related to increased extra-axial fluid spaces (IEAFS). Compared with the expected male frequency of 51.4% in newborns, there was a statistically significant overrepresentation of males in each of the 4 groups-65.3%, 62.2%, 62.6%, and 68.8%, respectively. We believe that the most likely explanation for these findings relates to the larger head size of the male compared with the female which has several relevant consequences. First, the larger head circumference of a male newborn compared with a female newborn may increase the likelihood that a male newborn will incur a small SDH from the minor trauma of the birthing process that can later rebleed and present with a symptomatic SDH that could be misdiagnosed as SBS and child abuse. Second, a short fall would have a greater likelihood of causing a SDH in a male infant than a female infant who could subsequently become symptomatic from hours to weeks later and could thus present as an unexplained SDH. Third, infants with macrocephaly related to IEAFS may be at increased risk for developing a SDH from the larger head size and greater tautness of the bridging vessels in the extra axial fluid spaces. We believe that many infants who have been diagnosed with SBS have been given incorrect diagnoses of child abuse. Rather, their SDH may occur as a result of a small SDH from the birthing process that enlarges during early infancy, a short fall, or from macrocephaly with IEAFS. PMID- 20308872 TI - The potential use of the eye temperature decrease in determining the time of death in the early postmortem period: studies in pigs. AB - The experiment was performed in pigs during which the postmortem body temperature was continuously measured. The study was focused on a period of time starting 0.5 hours after the animals' termination and consisted in computer recording of the cooling process of the eyeball (vitreous humor), orbit soft tissues, muscles, and the rectum. The experiment revealed the absence of a plateau phase of temperature decrease in eyeball and orbit soft tissues contrary to muscles and rectum, what demonstrates that temperature measurements in the eye could become an alternative method of determining the time of death during the initial phase of postmortem cooling. During this early postmortem period determination of the time of death based on measurements of the rectum or muscles temperatures due to existing plateau is not possible. PMID- 20308873 TI - "Authors" of dismemberment. PMID- 20308874 TI - Liposomal pegylated doxorubicin and oxaliplatin as salvage chemotherapy in patients with metastatic gastric cancer treated earlier. AB - The aim of this study was to evaluate the activity and safety of pegylated liposomal doxorubicin (PLD) and oxaliplatin (LOHP) as salvage chemotherapy in patients with metastatic gastric cancer (MGC) who had earlier been treated with docetaxel, capecitabine, 5-fluorouracil, and leucovorin. Treatment consisted of PLD (40 mg/m(2)) and LOHP (120 mg/m(2)) administered over 2 days, every 3 weeks. Response to therapy was assessed using the Response Evaluation Criteria In Solid Tumors; toxicity was evaluated by the National Cancer Institute common toxicity criteria (version 2.0). Thirty-six patients with pretreated MGC and a mean age of 66 years were recruited for the study. After a median follow-up of 11 months and 202 courses of chemotherapy administered (median, five courses per patient), the overall response rate in the 36 evaluable patients was estimated to be 28%. Grades 3 and 4 hematological toxicities were neutropenia in 44% of patients, grade 2-3 diarrhea in 14% of patients, and grade 2 neuropathy in 12 patients. Median progression-free survival and overall survival were 5.8 and 9.2 months, respectively, with 1-year survival rate of 36%, [95% confidence interval (CI): 21 54%]. Median survival time from the diagnosis of metastatic disease was 31.5 months. Seventy-two percent of patients (n=26) (95% CI: 58-88%) obtained a clinical benefit from this chemotherapy regimen. PLD and LOHP is an active regimen, able to give palliation in a substantial percentage of MCG patients who have been pretreated with taxanes. PMID- 20308875 TI - Short stature, severe aortic root dilation, skin hyperextensibility, extreme joint laxity and craniofacial dysmorphic features: a probable new syndrome. AB - We report a 10-year-old male proband, born from consanguineous marriage, presenting with short stature, severe aortic root dilation, skin hyperextensibility, extreme joint laxity and craniofacial dysmorphism. Clinical, biochemical and molecular findings did not match any of the well-described connective tissue syndromes in the differential diagnosis for this specific combination of features. We presume that the phenotype presented in this patient may constitute a newly recognized syndrome of likely autosomal recessive inheritance. PMID- 20308876 TI - Fibrin adhesive is better than sutures in pterygium surgery. AB - PURPOSE: To evaluate the recurrence rate, surgical time, and postoperative pain between conjunctival autografting with sutures and with fibrin adhesive in pterygium surgery. METHODS: A prospective, randomized, double-blind, clinical trial on the benefits of using fibrin adhesive in place of sutures in pterygium surgery. One hundred seventy-five eyes with primary pterygium were randomized to undergo pterygium surgery with conjunctival autograft transplantation using either fibrin adhesive or sutures. One hundred thirty-seven eyes of 113 patients that were operated on by a single surgeon (V.R.) completed the 1-year follow-up. Sixty-eight eyes were operated with fibrin adhesive and 69 eyes with sutures. Patients were followed up at 1 day, 1 week, 1 month, 6 months, and 1 year after surgery. Pterygium recurrence and postoperative pain was graded by an independent observer (A.L.) masked to the method of treatment. Surgical time was measured with a stopwatch. RESULTS: All patients were followed up for 1 year. There were 3 recurrences (4.41%) in the fibrin adhesive group and 11 recurrences (15.9%) in the suture group. The mean duration required to complete surgery in the fibrin adhesive group was 16.93 +/- 2.85 minutes, whereas that of the suture group was 29.84 +/- 5.65 minutes, which was statistically significant (P < 0.001). The immediate postoperative pain score and week 1 postoperative pain score were significantly lower in the fibrin adhesive group (P < 0.05). No major complications were observed in either group. CONCLUSION: The use of fibrin adhesive in primary pterygium surgery with conjunctival autografts reduces the recurrence rate, surgical time, and postoperative pain when compared with sutures. PMID- 20308877 TI - A comparison of endothelial cell loss after phacoemulsification in penetrating keratoplasty patients and normal patients. AB - PURPOSE: To compare phacoemulsification-related endothelial cell loss in transplanted corneas and normal corneas. METHODS: Forty-nine patients who underwent phacoemulsification/intraocular lens insertion after penetrating keratoplasty (PK-CAT group) (50 eyes) were compared with 65 patients who underwent phacoemulsification/intraocular lens insertion only (CAT group) (100 eyes). The PK-CAT group was divided into corneal endothelial dysfunction (CED) and opacity subgroups according to recipient endothelial function. Effective phacoemulsification time and endothelial density were analyzed. RESULTS: The endothelial cell density after cataract surgery from 1 month (1772.72 +/- 315.89) to 24 months (917.25 +/- 372.75) in the PK-CAT group was significantly lower than that before cataract surgery (2189.36 +/- 358.68) (P < 0.05) but that in CAT group was not significantly different from baseline during follow-up time (P < 0.05). The rate of graft survival in the opacity subgroup (82.0%) of the PK-CAT group was higher than that in the CED subgroup (54.5%) after 2 years (P < 0.05). The mean endothelial density in the opacity subgroup (1216.73 +/- 271.63 cells/mm2) of the PK-CAT group was significantly higher than that in the CED subgroup (632.50 +/- 238.29 cells/mm2) at 2 years after cataract surgery (P < 0.05). CONCLUSIONS: The phacoemulsification-related endothelial cell loss in transplanted corneas was higher than that in normal corneas. A possible factor contributing to higher endothelial cell loss in transplanted corneas is recipient endothelial dysfunction. PMID- 20308878 TI - Time-kill assay results for a linalool-hinokitiol-based eyelid cleanser for lid hygiene. AB - PURPOSE: Time-kill testing was performed for a linalool-hinokitiol-based eyelid cleanser against Pseudomonas aeruginosa, Moraxella catarrhalis, Escherichia coli, Serratia marcescens, Staphylococcus aureus, methicillin-resistant S. aureus (MRSA), Staphylococcus epidermidis, and Pityrosporum ovale to evaluate its efficacy. METHODS: An inoculum of 1 mL of each test organism culture was added to 49 mL of test cleanser. At 30 seconds and 1 minute, 1 mL of sample was removed from each test mixture and added to 9 mL of neutralizer. Five milliliters of aliquots were incubated for 48 hours and counted for colony-forming units. Ten percent povidone-iodine was used as a control. RESULTS: At 30 seconds, the linalool-hinokitiol-based eyelid cleanser produced a 99.9999% reduction in P. aeruginosa, a 99.999% reduction in E. coli, a 99.99% reduction in M. catarrhalis and S. marcescens, a 99.9% reduction in MRSA, a 99.2% reduction in S. epidermidis, and a 97.5% reduction in S. aureus. At 1 minute, this cleanser achieved a 95.8% reduction in P. ovale. At 30 seconds, povidone-iodine produced a 99.9999% reduction in P. aeruginosa and M. catarrhalis, a 99.999% reduction in S. marcescens and a 94.9% reduction in S. epidermidis. At 1 minute, 10% povidone iodine produced a 93.8% reduction in E coli but failed to produce a 1-log reduction in S. aureus or MRSA. CONCLUSIONS: This linalool-hinokitiol-based eyelid cleanser may be helpful in the outpatient setting for patients with presurgical, blepharitis, punctal plug and dry eye, and in the inpatient setting for patients who are allergic to iodine, or as an adjunct to povidone-iodine. PMID- 20308879 TI - Characteristics and outcome of patients with acute coronary syndrome and normal or near-normal coronary angiography. AB - INTRODUCTION: The incidence of normal or near-normal coronary angiography (NONCA) in patients undergoing coronary angiography, who have in patients with acute coronary syndrome (ACS) is reported between 1 and 12%. Earlier studies reported conflicting results regarding the nature and outcome of these patients. We used Acute Coronary Syndrome Israeli Survey (ACSIS), a biannually, nationwide ACS survey, as a source of unselected population representative of general clinical practice for the analysis and characterization of this group along the full spectrum of ACS. METHODS: This study uses patient data collected from ACSISs conducted in 2004, 2006, and 2008 in all the cardiology departments and coronary care units in Israel. Of the 5937 patients included in these surveys, 4060 (68.5%) had no earlier coronary interventions. Of these, complete angiographic data were available for 2903 patients who defines the study group. The rest of the patients were managed conservatively during the index hospitalization. On the basis of coronary angiography, 142 (4.9%) of the 2903 patients had no obstructive coronary artery disease (OCAD), 1895 (65.3%) had 1-2-vessel OCAD, 752 (25.9%) had 3-vessel OCAD, and 114 (3.9%) had left main disease. A comparison was made between the NONCA group and the OCAD group. RESULTS: When compared with the patients with OCAD, the NONCA patients were younger, more likely to be females, and had similar risk factors for OCAD. On admission, a higher incidence of chronic anticoagulants usage was noted in the NONCA group (5.6 vs. 2.0% in OCAD, P=0.04). One-quarter of the NONCA patients presented with ST-elevation on ECG as opposed to nearly half in the OCAD group (27.5 vs. 52.3% P<0.001). Most of the NONCA patients presented with normal or preserved left ventricular function on echocardiography, as compared with the significantly lower incidence of normal function in OCAD patients (77 vs. 45.5%, P<0.001). The NONCA patients were less likely to be treated with the recommended therapy for ACS, and this trend continued upon discharge. By stratifying the OCAD patients according to the number of diseased vessels, the NONCA patients had a similar mortality rate after 1 year, as the patients with 1-2-vessel OCAD (3.0 vs. 3.8, P=0.920). CONCLUSION: To our knowledge, this is the first study that explores the NONCA entity and its outcome along the full spectrum of ACS by using three nationwide, unbiased ACS surveys. These data indicate that, in discordance with common belief, NONCA patients share similar risk factors and outcome with the 1-2-vessels OCAD patients, but tend to be undertreated compared with the relevant ACS guidelines during, and more importantly, after the acute episode. Further follow-up is needed to establish their true long-term outcome. PMID- 20308880 TI - Coronary revascularization in patients with type 2 diabetes and results of the BARI 2D trial. AB - OBJECTIVES: This Perspective reviews the results of early and contemporary studies evaluating the safety and efficacy of coronary revascularization in patients with diabetes. It also addresses the implications of some of the data in the Bypass Angioplasty Revascularization Investigation in type 2 diabetes (BARI 2D) trial. METHODS: Review of the literature and discussion of the implications of results in the BARI 2D trial. RESULTS: Patients with diabetes benefit from revascularization by coronary thrombolysis, percutaneous transluminal coronary angioplasty, percutaneous coronary intervention (PCI), or coronary artery bypass grafting (CABG). However, with each intervention the benefit is less and the risks and complications are greater than in patients without diabetes. Revascularization for treatment of ST elevation myocardial infarction increases survival. When used for treatment of non-ST elevation myocardial infarction or unstable angina, it does not except in those at very high risk. In patients with chronic, symptomatic coronary artery disease, long-term mortality is comparable after CABG or PCI. However, the incidence of major adverse cardiac events is greater after PCI primarily because of the need for more subsequent revascularization procedures. Both interventions relieve symptoms, but neither improves survival except in patients at high risk. In patients with clinically stable chronic coronary disease, survival after CABG or PCI is comparable with that in patients treated with optimal medical therapy alone. Accordingly, evaluation for revascularization can be deferred until signs and symptoms worsen except in patients at high risk. In patients at high risk survival after promptly implemented CABG is greater than that with optimal medical therapy, especially when the diabetes is being treated with insulin sensitizing agents. PMID- 20308881 TI - Association between increasing levels of hemoglobin A1c and coronary atherosclerosis in asymptomatic individuals without diabetes mellitus. AB - BACKGROUND: Earlier studies have shown an association between high-normal glucose and increasing glycosylated hemoglobin (HbA1c) levels and cardiovascular events. The objective of this investigation was to study the association between increasing levels of HbA1c in asymptomatic individuals without diabetes mellitus (DM) and coronary plaque characteristics. METHODS: The study population consisted of 1043 asymptomatic Korean individuals without DM who underwent 64-slice cardiac computed tomography angiography as part of a health screening evaluation. We excluded 147 individuals with known history of DM and/or fasting glucose of at least 126 mg/dl, no HbA1c data, or missing risk factor information. The associations between coronary atherosclerosis and plaque subtype burden with increasing HbA1c levels were assessed using multivariable regression analyses. RESULTS: The final study population consisted of 906 individuals without DM (mean age: 49+/-9 years, 62% males); 19 and 9% of the population had any and two or more segments with coronary plaque, respectively. Unadjusted analysis showed a positive association between increasing levels of HbA1c and the number of coronary segments with any (P<0.001) and with mixed coronary plaques (P<0.0001). The association persisted even when traditional risk factors were taken into account. No significant relationship was found between increasing HbA1c levels and the burden of noncalcified or calcified plaque. CONCLUSION: Increasing levels of HbA1c in asymptomatic individuals without DM are associated with the presence of coronary atherosclerosis, but more specifically with the presence and burden of mixed coronary plaques. Elements of plaque instability have been associated with mixed coronary plaques. PMID- 20308882 TI - Impact of selective decontamination of the digestive tract on multiple organ dysfunction syndrome: systematic review of randomized controlled trials. AB - OBJECTIVE: We examined the impact of selective decontamination of the digestive tract on multiple organ dysfunction syndrome. DATA SOURCES: We searched MEDLINE, EMBASE, the Cochrane Register of Controlled Trials, previous meta-analyses, and meetings proceedings. STUDY SELECTION: We included all randomized trials comparing both oropharyngeal and intestinal administration of antibiotics in selective decontamination of the digestive tract with or without a parenteral component, with placebo or standard therapy used in the controls. DATA EXTRACTION: Two reviewers independently applied selection criteria, performed quality assessment, and extracted the data. The primary end point was the number of patients with multiple organ dysfunction syndrome developing during intensive care unit stay. Secondary end points were overall mortality and multiple organ dysfunction syndrome-related mortality. Odds ratios were pooled with the random effect model. DATA SYNTHESIS: We identified seven randomized trials including 1270 patients. Multiple organ dysfunction syndrome was found in 132 of 637 patients (20.7%) in the selective decontamination of the digestive tract group and in 219 of 633 patients (34.6%) in the control group (odds ratio, 0.50; 95% confidence interval, 0.34-0.74; p < .001). Overall mortality for selective decontamination of the digestive tract vs. control patients was 119 of 637 (18.7%) and 145 of 633 (22.9%), respectively, demonstrating a nonsignificant reduction in the odds of death (odds ratio, 0.82; 95% confidence interval, 0.51 1.32; p = .41). In five studies including 472 patients, multiple organ dysfunction syndrome-related mortality was demonstrated in 31 of 239 (13%) patients in selective decontamination of the digestive tract group and 37 of 233 (15.9%) in the controls (odds ratio, 0.84; 95% confidence interval, 0.48-1.41; p = .54). CONCLUSIONS: Selective decontamination of the digestive tract reduces the number of patients with multiple organ dysfunction syndrome. Mortality was not significantly reduced, probably because of the small sample size. PMID- 20308883 TI - Pretreatment with atorvastatin attenuates lung injury caused by high-stretch mechanical ventilation in an isolated rabbit lung model. AB - OBJECTIVE: We hypothesized that pretreatment with atorvastatin improves alveolar capillary permeability and hemodynamics and, thus, confers protection against lung injury caused by high-stretch mechanical ventilation. METHODS: Twenty-four isolated sets of normal rabbit lungs were utilized. Treated animals received atorvastatin (20 mg/kg body weight/day by mouth) for 3 days before surgery. Lungs were perfused constantly (300 mL/min) and ventilated for 1 hr with pressure control ventilation at either 23 (high pressure; resulting in tidal volume approximately 22 mL/kg) or 11 (low pressure; tidal volume approximately 10 mL/kg) cm H2O peak inspiratory pressure and positive end-expiratory pressure of 3 cm H2O. Four groups were examined: high pressure-no statin, high pressure-statin pretreatment, low pressure-no statin, and low pressure-statin pretreatment. RESULTS: The high-pressure-no statin group sustained more damage than the low pressure groups. In high-pressure groups, lungs of statin-pretreated vs. no statin-pretreated animals sustained a significantly lower increase in ultrafiltration coefficient (an accurate marker of alveolar capillary permeability; high-pressure-statin pretreatment vs. high-pressure-no statin, 0.013 +/- 0.017 g/min/mm Hg/100g vs. 1.723 +/- 0.495 g/min/mm Hg/100g; p < .001), lower weight gain (i.e., less edema formation; 4.62 +/- 1.50 grams vs. 17.75 +/- 4.71 grams; p = .005), improved hemodynamics (i.e., lower increase in mean pulmonary artery pressure; 0.56 +/- 0.51 mm Hg vs. 5.62 +/- 1.52 mm Hg; p = .04), lower protein concentration in bronchoalveolar lavage fluid (p < .001), and fewer histologic lesions (p = .013). Apoptosis of lung parenchyma cells was not different (p = .97). There was no difference between low-pressure-statin pretreatment and low-pressure-no statin groups regarding these outcomes. CONCLUSION: In this model, atorvastatin improves alveolar capillary permeability and hemodynamics and, thus, attenuates lung injury caused by high-stretch mechanical ventilation. PMID- 20308884 TI - High-dose renal replacement therapy for acute kidney injury: Systematic review and meta-analysis. AB - OBJECTIVE: To determine the effect of renal replacement therapy dose on mortality and dialysis dependence in patients with acute kidney injury. DATA SOURCES: MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials to October 2009; PubMed "Related Articles;" bibliographies of included trials; and additional information from trial authors. STUDY SELECTION: Randomized and quasi randomized, controlled trials in adults with acute kidney injury prescribed highvs. standard-dose continuous renal replacement therapy (> or =30 mL/kg/hr vs. <30 mL/kg/hr), intermittent hemodialysis, or sustained low-efficiency dialysis (daily vs. alternate day, or by target biochemistry). DATA EXTRACTION: Three authors independently selected studies and extracted data on outcomes and study quality. Meta-analyses used random-effects models. DATA SYNTHESIS: Of 5416 citations, 12 trials (n = 3999) met inclusion criteria. Modalities included continuous renal replacement therapy (7 trials), intermittent hemodialysis (3 trials), sustained low-efficiency dialysis (1 trial), and all three (1 trial). Study quality was moderate-high. Meta-analyses found no effect of high-dose renal replacement therapy on mortality (risk ratio, 0.89; 95% confidence interval, 0.77 1.03; 12 trials; n = 3954) or dialysis dependence among survivors (risk ratio, 1.15; 95% confidence interval, 0.92-1.44; 8 trials with events; n = 1743). The effect on mortality was similar (all interaction p values were nonsignificant) in patients with sepsis (risk ratio, 1.02; 95% confidence interval, 0.85-1.23; 9 trials; n = 1786) vs. without sepsis (risk ratio, 0.89; 95% confidence interval, 0.75-1.05; 8 trials; n = 1955), treated exclusively with continuous renal replacement therapy (risk ratio, 0.87; 95% confidence interval, 0.71-1.06; 7 trials; n = 2462) vs. other modalities alone or in combination (risk ratio, 0.92; 95% confidence interval, 0.70 -1.21; 5 trials; n = 1492), and in trials with low (risk ratio, 0.96; 95% confidence interval, 0.85-1.09; 6 trials; n = 3475) vs. higher (risk ratio, 0.76; 95% confidence interval, 0.53-1.09; 6 trials; n = 479) risk of bias. CONCLUSIONS: High-dose renal replacement therapy in acute kidney injury does not improve patient survival or recovery of renal function overall or in important patient subgroups, including those with sepsis. PMID- 20308885 TI - Long-term mortality and quality of life in sepsis: a systematic review. AB - BACKGROUND: Long-term outcomes from sepsis are poorly understood, and sepsis in patients may have different long-term effects on mortality and quality of life. Long-term outcome studies of other critical illnesses such as acute lung injury have demonstrated incremental health effects that persist after hospital discharge. Whether patients with sepsis have similar long-term mortality and quality-of-life effects is unclear. OBJECTIVE: We performed a systematic review of studies reporting long-term mortality and quality-of-life data (>3 months) in patients with sepsis, severe sepsis, and septic shock using defined search criteria. DESIGN: Systematic review of the literature. INTERVENTIONS: None. MAIN RESULTS: Patients with sepsis showed ongoing mortality up to 2 yrs and beyond after the standard 28-day inhospital mortality end point. Patients with sepsis also had decrements in quality-of-life measures after hospital discharge. Results were consistent across varying severity of illness and different patient populations in different countries, including large and small studies. In addition, these results were consistent within observational and randomized, controlled trials. Study quality was limited by inadequate control groups and poor adjustment for confounding variables. CONCLUSIONS: Patients with sepsis have ongoing mortality beyond short-term end points, and survivors consistently demonstrate impaired quality of life. The use of 28-day mortality as an end point for clinical studies may lead to inaccurate inferences. Both observational and interventional future studies should include longer-term end points to better understand the natural history of sepsis and the effect of interventions on patient morbidities. PMID- 20308887 TI - Timing of angiography after fibrinolysis for ST-elevation acute myocardial infarction. AB - PURPOSE OF REVIEW: Despite its limited efficacy in opening occluded coronary arteries in ST-elevation myocardial infarction, fibrinolysis remains the major reperfusion strategy used worldwide. Apart from bleeding, early reocclusion of the culprit artery is a common complication of the therapy and usually leads to a worse prognosis. RECENT FINDINGS: During the last 7 years routine percutaneous coronary intervention after fibrinolysis has been shown to improve early and long term outcome in six large randomized trials. SUMMARY: The optimal time window to perform percutaneous coronary intervention is between 3 and 24 h after fibrinolysis. PMID- 20308886 TI - Role of absolute lung volume to assess alveolar recruitment in acute respiratory distress syndrome patients. AB - OBJECTIVE: It is commonly assumed that lung volume at zero end-expiratory pressure (functional residual capacity) is not affected by positive end expiratory pressure (PEEP) even in presence of alveolar recruitment, and it is often ignored when measuring lung recruitment by pressure-volume curves. Aim of the study was to investigate the effect of PEEP on functional residual capacity, and quantify the error of considering equal functional residual capacity in measuring alveolar recruitment. DESIGN: Interventional human study. SETTING: A 10 bed general intensive care unit in a university hospital. PATIENTS: Ten sedated, curarized, mechanically ventilated acute respiratory distress syndrome patients. INTERVENTIONS: Three levels of PEEP (5, 10, and 15 cm H2O), were randomly applied, for 1 hr each. MEASUREMENTS AND MAIN RESULTS: At each PEEP we obtained a pressure-volume curve, the volume expired from PEEP to zero pressure (PEEP related lung volume) and functional residual capacity by helium dilution method. Functional residual capacity increased at increasing PEEP levels. Functional residual capacity was 507 +/- 292, 607 +/- 311, and 681 +/- 312 ml (p < .05), respectively, at PEEP 5, 10, and 15 cm H2O. Pressure-volume curves were aligned starting from PEEP related lung volume (relative volume method) or from end expiratory lung volume at PEEP (absolute volume method). Recruitment was measured as vertical distance of pressure-volume curves at 20 cm H2O airway pressure. The relative volume method led to underestimation of recruitment (43 +/- 28% and 35 +/- 18 %, respectively, at PEEP 10 and 15). CONCLUSIONS: Functional residual capacity is affected by PEEP. Ignoring this effect leads to relevant underestimation of alveolar recruitment as measure by pressure-volume curve displacement. PMID- 20308888 TI - The genetic landscape from single gene to polygenic disorders. PMID- 20308889 TI - New diagnostic devices in heart failure. AB - PURPOSE OF REVIEW: Heart failure is among the leading causes of morbidity and mortality in the United States. In recent years, implantable devices have been developed that aim to predict impending heart failure events in time to prevent clinical decompensation. This review focuses on these emerging technologies and the implications they hold for the future of heart failure management. RECENT FINDINGS: Many devices have recently been studied in patients with heart failure. These devices either evaluate hemodynamic values, including pulmonary and left atrial pressures, or intrathoracic impedance, which is related to pulmonary congestion. In small trials, device-acquired parameters like these have correlated well with data obtained during pulmonary artery catheterization. At least one trial has suggested a possible reduction in clinical heart failure events in patients with a device measuring pulmonary pressures. Other trials, recently completed or ongoing, are expected to shed more light on the role of diagnostic devices in improving heart failure outcomes. SUMMARY: Incorporation of diagnostic devices into the management of heart failure patients may prove instrumental in reducing the burden of this disease on patients and healthcare systems. PMID- 20308890 TI - Role of the polycomb group gene BMI1 in normal and leukemic hematopoietic stem and progenitor cells. AB - PURPOSE OF REVIEW: The polycomb group gene BMI1 fulfills essential roles in both normal and leukemic stem cells. The underlying molecular mechanisms are beginning to become unraveled and an overview of the current knowledge on BMI1 signaling in normal and leukemic stem cells will be presented here. RECENT FINDINGS: In addition to a role in bypassing senescence and the orchestration of the symmetry of hematopoietic stem cell divisions, it has recently become clear that BMI1 also functions in the protection against oxidative stress. In the absence of BMI1, reactive oxygen species accumulate, associating with activation of DNA damage response pathways and increased apoptosis. BMI1-mediated control over reactive oxygen species levels might occur independently of the INK4a/ARF pathway, but rather involves impaired mitochondrial functions. In human hematopoietic malignancies, BMI1 is frequently overexpressed, which associates with poor prognosis. Down modulation of BMI1 impairs self-renewal and long-term expansion of leukemic stem cells. SUMMARY: Understanding molecular mechanisms by which BMI1 affects stem cell fate will increase our insights into the biology of hematopoietic stem cells and will also aid in understanding the process of leukemic transformation and ultimately in the identification of drugable targets that might facilitate the eradication of leukemic stem cells. PMID- 20308892 TI - Role of myeloid cells in vascular endothelial growth factor-independent tumor angiogenesis. AB - PURPOSE OF REVIEW: Targeting the vascular endothelial growth factor (VEGF) pathway has had a significant impact in the therapy of cancer and intraocular neovascular disorders. Similar to other therapies, inherent/acquired resistance to anti-VEGF drugs may occur in cancer patients, leading to disease recurrence. This review describes recent findings on the role of myeloid cells in refractoriness or/and acquired resistance to such therapies. RECENT FINDINGS: Various myeloid cell types, including tumor-associated macrophages, Tie2 expressing monocytes and neutrophils, have been implicated in tumor angiogenesis. Several cytokines involved in the mobilization and/or proangiogenic effects of these cells represent therapeutic targets. CD11b+Gr1+ myeloid cells have been shown to render tumors refractory to angiogenic blockade by VEGF antibodies. This effect was mediated by the secreted protein Bv8, which is upregulated by granulocyte colony-stimulating factor. SUMMARY: Progress in unraveling proangiogenic mechanisms dependent on various myeloid cell types has expanded our understanding of tumor angiogenesis and has generated a number of potential therapeutic targets. PMID- 20308891 TI - Mechanisms of vascular stability and the relationship to human disease. AB - PURPOSE OF REVIEW: The genetic basis for a variety of vascular malformation syndromes have been described, with an increasing functional understanding of the associated genes. RECENT FINDINGS: Genes responsible for familial vascular malformation syndromes have increasingly been shown to be involved in the control of vascular stability. SUMMARY: Genes involved in vascular stability pathways are good candidates for causing vascular malformation syndromes. Although these findings confirm the biologic importance of the involved pathways, further explanations are required to describe the focal nature of disease. PMID- 20308893 TI - Hypoxia-driven angiogenesis: role of tip cells and extracellular matrix scaffolding. AB - PURPOSE OF REVIEW: Angiogenesis is a highly coordinated tissue remodeling process leading to blood vessel formation. Hypoxia triggers angiogenesis via induction of expression of growth factors such as vascular endothelial growth factor (VEGF). VEGF instructs endothelial cells to form tip cells, which lead outgrowing capillary sprouts, whereas Notch signaling inhibits sprout formation. Basement membrane deposition and mechanical cues from the extracellular matrix (ECM) induced by hypoxia may participate to coordinated vessel sprouting in conjunction with the VEGF and Notch signaling pathways. RECENT FINDINGS: Hypoxia regulates ECM composition, deposition, posttranslational modifications and rearrangement. In particular, hypoxia-driven vascular remodeling is dynamically regulated through modulation of ECM-modifying enzyme activities that eventually affect both matricellular proteins and growth factor availability. SUMMARY: Better understanding of the complex interplay between endothelial cells and soluble growth factors and mechanical factors from the ECM will certainly have significant implications for understanding the regulation of developmental and pathological angiogenesis driven by hypoxia. PMID- 20308894 TI - Cardiac risk evaluation for abdominal transplantation. AB - PURPOSE OF REVIEW: Cardiovascular disease has emerged as a leading cause of perioperative morbidity and mortality in renal and liver transplant patients. There is no consensus on how to diagnose cardiac disease in transplant patients. Further, there is significant disagreement in the literature regarding the use of routine screening methods to detect disease. This review will explore published observations on cardiac complications in renal and liver transplant patients to try and determine why investigators hold such divergent opinions. RECENT FINDINGS: The prevalence of cardiac disease is greater in renal and liver transplant patients than in the general public. Complications of cardiac disease play a large role in early mortality and graft loss in the postoperative period. While the presence of risk factors seems to predict coronary disease in renal disease, these factors do not perform as well in liver disease. Noninvasive stress testing for coronary artery disease seems to have low sensitivity in both transplant populations. However, the measurement of cardiac troponin seems to be of some value in predicting early mortality. SUMMARY: Physicians have not identified an effective yet cost-effective way to screen transplant patients for cardiac disease. Therefore, the first step in creating widely accepted protocols demand that physicians decide what predictive power that screening tests should have in this unique population. PMID- 20308895 TI - Anesthesia and outcome after partial hepatectomy for adult-to-adult donor transplantation. AB - PURPOSE OF REVIEW: The worldwide adoption of live liver donors as a source of donor organs for transplantation has been curtailed by the very real risk of complications in otherwise healthy people. Our objective in this review is to outline the perioperative management of the live liver donor for adult-to-adult transplantation. RECENT FINDINGS: The incidence and severity of complications following live liver donation is extremely variable, and reporting needs to be standardized if we are to improve the perioperative management and outcomes. Agreed definitions would clarify the incidence and severity of postoperative complications, allow identification of areas in which management can be improved and suggest areas for future investigation. Such an effort will require the cooperation of centers around the world. SUMMARY: Live liver donation is a valuable option for organ donation that can be conducted safely with a multidisciplinary perioperative approach. Future considerations should focus on the recovery period and how the intraoperative management can be optimized to minimize the impact of surgery on donors' quality of life. PMID- 20308896 TI - Sodium, potassium and glucose management in organ transplantation. AB - PURPOSE OF REVIEW: To present current knowledge about the metabolic management of patients undergoing solid organ transplantation, and potential organ donors. RECENT FINDINGS: Appropriate management of electrolytes and glucose improves outcome after transplantation, although conflicting evidence exists. Patients with cirrhosis-induced hyponatremia can be successfully transplanted but are at increased risk of postoperative complications. A new class of drugs, the vaptans, that antagonizes arginine vasopressin may be an effective treatment for hyponatremia in transplant candidates. Recent literature has documented the implications, predictors and potential therapies for perioperative hyperkalemia in the transplant population. The debate over appropriate targets for serum glucose in perioperative and critically ill patients has been lively. The documented risk of hypoglycemia associated with 'intensive insulin therapy' has led to the adoption of more conservative glycemic targets. Studies of glycemic control in transplant recipients are limited. SUMMARY: In patients undergoing solid organ transplants, sodium management should aim to minimize an acute change in sodium concentration. Vaptans may be of future use in optimizing patients with cirrhosis prior to transplantation. Pending further studies, a perioperative 'middle ground' target glucose of between 140 and 180 mg/dl seems reasonable at this time. PMID- 20308897 TI - Psychological outcomes with face transplantation: overview and case report. AB - PURPOSE OF REVIEW: The purpose of this review is to provide guidance in a burgeoning new field of facial composite tissue transplantation. This review will contrast face transplant with solid organ transplantation, provide information to guide selection of face transplant candidates, and share information on psychological outcomes. RECENT FINDINGS: Previously published face transplant reports have not investigated body image, mood changes, perception of teasing, quality of life, self-esteem, or social reintegration quantitatively. Face transplantation appears to decrease depression and verbal abuse, and improve quality of life and social reintegration, though may not alter anxiety or self esteem. The Psychosocial Adjustment for Illness Scale-Self-Report scale may have advantages over the SF-36 and World Health Organization Quality of Life (WHOQOL) BREF rating scales for measuring psychological distress and social reintegration. SUMMARY: Face transplantation is currently a technique of last resort after traditional reconstructive techniques have failed, not for cosmesis alone. Mortality among eight existing face transplant patients is 25%, two of eight. Some consider blindness as an absolute contraindication; however, those who are legally blind but retain some vision may be appropriate candidates. Physical goals of transplantation include regaining movement of underlying structures and restoring the appearance of a normal face. However, psychological outcomes and quality of life are also important to the success of face transplantation and ultimately will determine the value of the procedure. PMID- 20308898 TI - Depersonalization disorder. AB - PURPOSE OF REVIEW: There is increasing interest in depersonalization disorder, in part because of the increased community awareness of the condition via the Internet. The disorder may be more prevalent than schizophrenia but is often misdiagnosed; hence, an update is timely. RECENT FINDINGS: Recent research has included characterization of the nosology and phenomenology of the disorder, whereas emerging evidence demonstrates a neurophysiological dampening down in addition to psychological dampening in the face of emotional stimulation. SUMMARY: Greater understanding of the clinical characteristics of this disorder will improve the reliability of diagnosis and aid the development of neurobiological and psychological models for empirical testing. Although response to current treatments has been disappointing, recent research has identified the basis for the development of new pharmacological and psychological treatments. PMID- 20308899 TI - Localizing performance of go/no-go tasks to prefrontal cortical subregions. AB - PURPOSE OF REVIEW: Response inhibition is an essential executive function implemented by the prefrontal cortex. Performance of go/no-go tasks, which are frequently used to investigate response inhibition, recruits a variety of cognitive components besides response inhibition. This article reviews recent findings on the functional localization associated with go/no-go tasks. RECENT FINDINGS: Recent neuropsychological and neuroimaging studies have shown that the presupplementary motor area and ventrolateral prefrontal cortex are crucial for response inhibition and that various subregions of the prefrontal cortex make different contributions leading to successful response inhibition. In particular, functional dissociation has been identified in the right ventrolateral prefrontal cortex, which consists of at least three subregions: the posterior part of the inferior frontal gyrus, inferior frontal junction and inferior frontal gyrus/insula. SUMMARY: Neuropsychological studies provide strong evidence that separate subregions of the prefrontal cortex make critical contributions to specific cognitive components involved in response inhibition, whereas neuroimaging studies cannot provide direct evidence regarding the causality, but provide insights into functional localization with high spatial resolution. These methods contribute significantly to our understanding of how executive functions are implemented and should continue to do so into the future. PMID- 20308900 TI - The effects of early adversity on the adult and developing brain. AB - PURPOSE OF REVIEW: Recent advances in neuroimaging methods have provided new ways of unravelling the complex interplay between genetic and environmental factors that influence functional brain development in the critical first years of life. This has allowed new insights into the effects that early adverse experience can exert on the brain later in life. We review recent progress in the characterization of those effects and underlying mechanisms through which adverse environment influences the neurocognitive development. RECENT FINDINGS: Socioeconomic background may have a profound effect on structural and functional brain development, especially in the domains of language and prefrontal executive control. These effects are mediated by several factors: diet, quality of parental care, impoverished environment, prenatal exposure to toxic substances and so on. Other circumstances such as perinatal brain injury, early sensory deprivation or limb malformation may result in atypical functional organization of the brain and lasting cognitive impairment of certain functions. Early experience of maltreatment or institutionalized care may alter the development of the social brain, contributing to negative mental health outcomes, which may be partially reversed through early intervention programmes. SUMMARY: Subsequent models of psychiatric disorder should take into account early risk factors and embrace developmental models at multiple levels of biological organization. There is a continuing need for the study of optimal environmental input during sensitive periods in brain development. PMID- 20308901 TI - Review of HIV and HCV infection among drug users in China. AB - PURPOSE OF REVIEW: Drug abuse has resulted in a huge public health and economic burden in China, especially the rapid spread of HIV/AIDS and hepatitis C virus (HCV) infection. Multiple HIV and HCV subtypes were detected among drug users in China, this study reviews the molecular distribution of HIV and HCV among injection drug users (IDUs) and explores new epidemiologic trends of HIV and HCV among drug users in China. RECENT FINDINGS: The 2009 National Narcotic Control Commission report showed that the percentage of users of 'new-type drugs', including amphetamine-type stimulants (ATS: methamphetamine and MDMA/ecstasy) and ketamine, was about 27% of total drug users. The pooled data from published papers showed that CRF07BC was the predominant HIV-1 subtype, which accounted for 38.8%, and it was followed by AE, which accounted for 22.7% among HIV-positive IDUs. Following these, the CRF08BC, B' and C subtypes accounted for about 10.8%, 9.9% and 9.2%, respectively. Subtype 6a was the predominant HCV subtype, accounting for 36.7%, and subtypes 3b, 1a, 3a and 1b were the next most predominant subtypes. SUMMARY: With the increase of 'new-type drugs' use and AE HIV-1 subtype infection among IDUs, the situation regarding HIV/AIDS and HCV infection has become complicated. More comprehensive prevention and intervention strategies should be instigated for the extensive high-risk populations in China. PMID- 20308902 TI - The intersecting risks of substance use and HIV risk among substance-using South African men and women. AB - PURPOSE OF REVIEW: The aim of this article is to review the recent literature examining the intersection between alcohol and other drug use and HIV risk behaviors for South African men and women, and the implications for the development of interventions and future research. RECENT FINDINGS: The current literature indicates that substance use in sexual contexts (i.e. before or during sex) as well as outside of the sexual context is associated with HIV risk behaviors, such as having unprotected sex and multiple sex partners. Additionally, environments where substances are used, such as drinking establishments, may be associated with HIV risk behaviors. Moreover, sexual violence is also associated with substance use. Brief HIV prevention interventions to address substance use have demonstrated promising findings - such as consistent condom use, less impaired sex, and less unprotected vaginal and anal intercourse - when compared with other interventions. SUMMARY: Recent research findings support the previous literature concerning the link between substance use and HIV risk behaviors in South Africa and suggest the need for interventions focused on sexual risk behaviors in the context of substance use and the environments in which they are used. PMID- 20308903 TI - Sexual and drug use behaviors associated with HIV and other sexually transmitted infections among female sex workers in the Mexico-US border region. AB - PURPOSE OF REVIEW: The purpose of this review is to summarize the latest research regarding HIV/sexually transmitted infection (STI) risk among female sex workers (FSWs) along the Mexico-US border. Although Mexico has a low prevalence of HIV overall, HIV prevalence among FSWs in Tijuana is quite high, and even higher among FSWs who inject drugs (FSW-IDUs). Efforts to better understand and curtail the HIV epidemic among FSWs in this region are greatly needed. RECENT FINDINGS: A brief HIV/STI risk reduction intervention for FSWs was successful in decreasing HIV/STI sexual risk behavior with clients among FSWs in Tijuana and Ciudad Juarez, Mexico. However, the intervention was less effective among FSW-IDUs, and had no effect on FSWs' condom use with their noncommercial partners. Whereas the majority of research thus far has focused on FSWs' individual-level risk factors, comparatively less is known about their clients and noncommercial sexual partners who may heavily influence their behavior, and engage in high-risk behaviors themselves. SUMMARY: Further studies including FSWs' intimate partners and clients are needed as well as interventions specific to FSW-IDUs. Targeting the most at-risk populations and reducing both sexual and injection-risk behaviors simultaneously may curb the growing HIV epidemic in the Mexico-US border region. PMID- 20308904 TI - Alcohol and drug use in suicidal behaviour. AB - PURPOSE OF REVIEW: To present a summary of estimates of the risk of suicidal behaviour (ideation, plan and attempt) among those with substance use disorders in the general population and risk estimates for those with acute alcohol and drug consumption (intoxication) immediately prior to a suicide attempt. RECENT FINDINGS: In Mexico and elsewhere studies have emerged on the risk of suicidal behaviour among those with substance use disorders that are not affected by treatment selection bias or by psychiatric comorbidity. In developed and developing groups of nations, alcohol use disorders were associated with increased odds ratio (OR) of ideation (range 2.0-2.5) and attempt (2.6-3.7), whereas drug use disorders were associated with increased risk of ideation (2.3 3.0) and attempt (2.0-4.0). Follow-up studies of general population samples reported an OR for drug use disorders from 1.9 to 3.7 for ideation, and an OR of 3.0 for attempt. Alcohol dependence increased suicide ideation with an OR of 1.5. Those drinking alcohol prior to the suicide attempt had ORs in the range of 6.2 9.6. This increase may have a dose-response relationship. We found no studies providing risk estimates for drug use prior to a suicide attempt. SUMMARY: Current evidence points to a causal role of alcohol and drug use disorders exerting a distal effect on suicidal behaviour. Evidence for the proximal role of alcohol and drug use, as triggers of suicidal behaviour, are still very limited in number, analytical techniques and scope of substances other than alcohol. PMID- 20308905 TI - Substance abuse among Iranian high school students. AB - PURPOSE OF REVIEW: In this study, we reviewed data on drug use among high school students in Iran. RECENT FINDINGS: Published epidemiological studies in international and domestic journals show that drug use/abuse is a serious mental health problem in Iran. There is cultural support for opium in Iran and also there is cultural tolerance for tobacco smoking, especially as water pipe smoking in Iranian families. Alcohol, opium and cannabis are the most frequently used illicit drugs, but there are new emerging problems with anabolic steroids, ecstasy and stimulant substances, such as crystal methamphetamine. SUMMARY: There is a serious drug abuse problem among Iranian high school students. It could be due to role modeling by parents - mainly fathers - and also cultural tolerance of some substances. Early onset of tobacco smoking, with a daily use rate between 4.4 and 12.8% in high school students, is an important risk factor for other drug abuse problems. Use of all types of drugs, except prescription drugs, is more prevalent among boys. Alcohol is the most frequently abused substance, with a lifetime rate of at least 9.9%. Lifetime rates of opiate use - mostly opium - was between 1.2 and 8.6% in different parts of the country. As drug abuse is a frequent problem among Iranian high school students, it is necessary to design and implement drug prevention programs to protect them. Such programs, including life skills training and drug education, have been operating in recent years for Iranian students from kindergarten to the university level. PMID- 20308906 TI - Comparison of central and mixed venous saturation during liver transplantation in cirrhotic patients: a pilot study. AB - BACKGROUND AND OBJECTIVE: Liver transplantation is associated with important haemodynamic variations requiring cardiac output and oximetric data monitoring. The mixed venous saturation (SvO2) integrates parameters combining information about oxygen consumption, cardiac output and haemoglobin concentration. Central venous saturation (ScvO2) can be directly measured from blood drawn in the superior venous system via a central venous catheter. ScvO2 has been proposed as an alternative to SvO2 for intraoperative haemodynamic monitoring. The aim of the present study was to examine the level of agreement between SvO2 and ScvO2 during the preanhepatic and the neohepatic stage of liver transplantation in cirrhotic patients. MATERIALS AND METHODS: After agreement from the regulatory authorities for medical research and having obtained informed consent, 30 patients with cirrhosis undergoing liver transplantation were prospectively included. Blood gas samples were simultaneously drawn from the arterial line, the right atrium port and the pulmonary artery port of the catheter: during the preanhepatic stage (two times) and two times 30-40 min after graft revascularization. Arterial saturation (SaO2), haemoglobin concentration, cardiac index, SvO2, ScvO2 and oxygen consumption, delivery and extraction (VO2, DO2 and EO2, respectively) were measured. A Bland-Altman test was used to determine bias and limits of agreement between SvO2 and ScvO2. Both parameters were considered to be equivalent if limits of agreement were within +/-5%. RESULTS: Bland-Altman analysis revealed a bias (limit of agreement) of -1.2% (-9.1 to 6.6%), -0.3% (-4.8 to 4%) and -2.1% ( 12 to 7.8%) for the overall measurements and preanhepatic and postgraft reperfusion measurements, respectively. SvO2 decreased significantly between hepatectomy and reperfusion, whereas cardiac index, VO2, DO2 and EO2 showed significantly higher values after reperfusion. ScvO2 and SaO2 levels did not display different values between the two periods. DISCUSSION: Measurements of SvO2 and ScvO2 showed a good level of agreement during the preanhepatic stage, whereas the level of agreement was low after liver graft reperfusion. The increase of VO2 associated with the decrease of SvO2 and the stability of ScvO2 between the two periods suggest an incomplete mixing of splanchnic venous blood into the right atrium. In addition, our samples were taken from the right atrium, which is not possible using a conventional central venous catheter, as the tip must lie in the superior vena cava and not in the right atrium. ScvO2 cannot be considered equivalent to SvO2 for the haemodynamic monitoring of patients with cirrhosis undergoing liver transplantation. PMID- 20308907 TI - Comparative evaluation of propofol 350 and 200 mg for induction of anaesthesia in morbidly obese patients: a randomized double-blind pilot study. AB - BACKGROUND AND OBJECTIVE: The aim of this pilot study was to evaluate efficacy and safety of propofol 350 versus 200 mg for induction of anaesthesia in morbidly obese patients undergoing bariatric surgery. PATIENTS AND METHODS: Twenty morbidly obese patients (BMI range 38-60 kg m) were randomized to receive propofol 350 or 200 mg over 60 s for induction of anaesthesia. Bispectral index (BIS) values, induction characteristics and haemodynamic parameters were compared. RESULTS: At the time of intubation, in the 200 mg group, mean BIS values were more variable and significantly higher [53 (range 27-86) versus 31 (range 18-52), 200 versus 350 mg group (P = 0.01)]. In 20% of the 200 mg group, an additional propofol dose was needed, whereas no additional doses were judged necessary in the 350 mg group. At the time of intubation, six patients in the 200 mg group had systolic arterial pressures above 160 mmHg [mean 162 (range 100 210)], whereas mean pressures in the first 10 min were more in the target range in the 350 mg group [mean 122 (range 90-170)] (P = 0.01). One patient in the 350 mg group experienced a serious decrease in systolic arterial pressure (below 60 mmHg), immediately upon starting the maintenance dose. There were no significant differences in heart rate. CONCLUSION: Although propofol 200 mg proved to be an inadequate induction dose for morbidly obese patients, the 350 mg induction dose deserves further study, provided the maintenance dose is not started within 5 min, thereby preventing temporary cardiovascular instability. PMID- 20308909 TI - The lexicon of 'Cardiac Rehabilitation': is it time for an evolutionary new term? PMID- 20308908 TI - Blood pressure and antihypertensive therapy according to the global cardiovascular risk level in Italy: the CHECK Study. AB - BACKGROUND: Elevated blood pressure (BP) is one of the most important modifiable risk factors for cardiovascular diseases. In this study we assessed the excess of cardiovascular risk attributable to high BP and antihypertensive treatment in a sample of Italian patients enrolled by the 'Cholesterol and Health: Education, Control and Knowledge' (CHECK) study. METHODS: CHECK is a large, cross-sectional epidemiological study, which randomly enrolled patients aged 40-79 years from 425 Italian General Practices from March 2002 to April 2004. Among 5731 patients enrolled in the study [49.6% men, mean age (standard deviation) 57.7 (10.3) years], 723 (12.6%) had 'optimal' BP, 1496 (26.1%) had 'high normal' BP, and 1942 (33.9%) were hypertensive. RESULTS: According to the European Guidelines stratification of the cardiovascular risk-excess attributable to high BP, 34.7% of the sample had a low added risk and 53.2% had a moderate-to-very high added risk. The pharmacological therapy was prescribed in 22.3, 43.9, 61.4, and 76.9% of the patients with low, moderate, high, and very high added risk, respectively. CONCLUSION: Overall dietary and drug therapies are under prescribed, as most of the treated patients would require two additional antihypertensive drugs to meet the recommended BP target. This effort could provide significant individual benefit to moderate/high-risk patients. PMID- 20308910 TI - Feasibility and long-term evolution of TIPS in cirrhotic patients with portal thrombosis. AB - AIM: Many researchers consider portal thrombosis (PT) as a contraindication to transjugular intrahepatic portosystemic shunt (TIPS). The aim of this retrospective study was to compare the feasibility and long-term prognosis of TIPS in cirrhotic patients, with and without, complete PT. PATIENTS AND METHODS: Four hundred and thirty-six consecutive cirrhotic patients with portal hypertension were referred for TIPS, between 1990 and 2004. These patients were divided into two groups according to their portal patency. PT+: 34 patients with complete PT with cavernoma (19) or without (15) cavernoma versus PT-: 402 patients with normal portal patency (308) and partial PT (94). Epidemiological data were compared using the chi and Student's t-tests, and comparative evolution was made from actuarial data using the log-rank test. RESULTS: PT+ patients were more frequently women with viral hepatitis, and TIPS was performed more often for bleeding indications. The TIPS success rate was significantly lower in the PT+ group (79%) than in the PT- group (99.5%) (P<10). Presence of a cavernoma decreased the success rate to 63%. TIPS was always feasible in cases of recent PT and portal cavernoma with an accessible intrahepatic patent portal branch. Early and late outcome and complications were not significantly different between the two groups. CONCLUSION: Complete PT does not modify TIPS' long-term outcome. Rather than a contraindication, PT should be considered as an indication for TIPS in cirrhotic patients with accessible intrahepatic portal vein. Further randomized studies should be planned in cirrhotic patients with recent PT to better qualify TIPS and anticoagulation indications, respectively. PMID- 20308911 TI - The angiotensin-converting enzyme insertion/deletion polymorphism modifies the clinical outcome in patients with Pompe disease. AB - PURPOSE: The insertion/deletion polymorphism of angiotensin-converting enzyme may influence muscle properties. We examined whether Pompe disease clinical manifestations, which are known to be highly variable among late-onset patients, may be modulated by angiotensin-converting enzyme polymorphism. METHODS: We included 38 patients with late-onset Pompe disease, aged 44.6 +/- 19.8 years. We compared the distribution of angiotensin-converting enzyme polymorphism according to demographic and disease parameters. RESULTS: The distribution of angiotensin converting enzyme polymorphism was in line with the general population, with 16% of patients carrying the II genotype, 37% carrying the DD genotype, and the remaining patients with the ID genotype. The three groups did not differ in mean age, disease duration, Walton score, and other scores used to measure disease severity. The DD polymorphism was associated with earlier onset of disease (P = 0.041), higher creatine kinase levels at diagnosis (P = 0.024), presence of muscle pain (P = 0.014), and more severe rate of disease progression (P = 0.037, analysis of variance test for interaction). DISCUSSION: These findings suggest a potential role of angiotensin-converting enzyme polymorphism in modulating Pompe disease phenotype and prognosis. PMID- 20308912 TI - Health-related quality of life in the family caregivers of stroke survivors. AB - The objective of this cross-sectional study was to identify the factors associated with health-related quality of life (HRQOL) of family caregivers of Chinese stroke patients. One hundred and twenty-three stroke patients consecutively admitted to a stroke clinic and their 123 family caregivers were recruited. The caregivers' HRQOLs were assessed with the Short Form 36 (SF-36). Two subscores of the SF-36, the Physical Component Summary and the Mental Component Summary Scores served as the dependent variables. Independent variables comprised patients and caregivers' demographic data and physical and psychological conditions in relation to caregivers' HRQOL. The severity of coexisting illnesses of both the patients and their caregivers was assessed using the Cumulative Illness Rating Scale. The Geriatric Depression Scale (GDS) was administered to rate both the patients and their caregivers' depressive symptoms. The extent of the patients' functional disability was assessed using the Barthel Index and the Instrumental Activities of Daily Living. Global cognition of the patients was measured using the Mini Mental State Examination. The level of social support and recent life events of the caregivers were rated using Lubben Social Network Scale and the Modified Life Event Scale, respectively. The multiple linear regression revealed caregivers' Cumulative Illness Rating Scale and GDS score were associated with Physical Component Summary Score of SF-36. The patients and caregivers' GDS score were associated with Mental Component Summary Score of SF-36. Severity of depressive symptoms in Chinese stroke patients and their caregivers is an important factor associated with the caregivers' HRQOL. Further studies evaluating interventions on caregivers' HRQOL should include the assessment and management of mood disorders. PMID- 20308913 TI - Pacemaker implantation in a patient with persistent left superior vena cava using a steerable catheter-delivered lead. PMID- 20308914 TI - Alcoholic cardiomyopathy. AB - The myocardial depressant effects of excessive ethanol consumption have long been known. Excessive alcohol intake is reported in a wide range (3-40%) of patients with idiopathic dilated cardiomyopathy; furthermore, chronic excessive alcohol consumption may lead to progressive and chronic cardiac dysfunction and can be a possible cause of dilated cardiomyopathy, referred to as alcoholic cardiomyopathy (ACM). The pathophysiological mechanisms underlying ACM are poorly understood. Excessive alcohol consumption has been associated with left-ventricular myocyte loss in some animal models but not in all studies. In addition, heavy drinking may cause myocyte dysfunction, due to abnormalities in calcium homeostasis, and cause elevated levels of norepinephrine. Increasing doses of ethanol have been associated with a negative inotropic effect on myocytes in animal experiments. In this review, we evaluate the epidemiology, current pathophysiological mechanisms and possible role of factors that influence ACM and discuss its clinical presentation, prognosis and treatment. PMID- 20308915 TI - Refractory acute decompensated heart failure: an observational study on a noninvasive hemodynamic monitoring system aimed at improving the therapeutic approach. AB - BACKGROUND: Inotropic agents should only be administered in acute decompensated heart failure (ADHF) refractory to vasodilators at optimal doses because they are associated with adverse outcome. In this setting a noninvasive hemodynamic monitoring system (NHMS) could be useful for optimizing treatment. METHODS: INCLUSION CRITERIA: advanced chronic heart failure, ejection fraction 30% or less, admission for ADHF with systolic blood pressure 115 mmHg or less and inadequate response at 48 h of therapy. Patients were evaluated with a NHMS: with vascular systemic resistance (VSR) greater than 1500 dyne x s/cm we used vasodilators at increasing doses, with VSR less than 1500 and cardiac index (CI) less than 2.4 l/min per m inotropic agents were used. RESULTS: The study population consisted of 20 patients (mean age 67 + or - 12 years) with ejection fraction 20 + or - 7%. After 48 h of clinical-guided therapy, none of the patients achieved VSR 1500 or less, and 12 patients had a CI less than 2.4 l/min per m. After hemodynamic-guided therapeutic optimization there was a significant reduction of dyspnea at rest (7.7 + or - 1.25 versus 2.44 + or - 1.33 on the 10 point Likert scale, P < 0.001) and 'cold' presentation (12 patients before and 1 patient after, P = 0.0004). Daily urinary volume was higher (1217 + or - 369 versus 2260 + or - 797 ml, P = 0.001) without renal function deterioration (creatinine 1.56 + or - 0.52 versus 1.34 + or - 0.61 mg/dl, P = 0.012).The nitroprusside dosing was increased after NHMS (0.13 + or - 0.19 versus 0.4 + or - 0.310 microg/kg per min, P = 0.044), whereas doses of inotropic agents, diuretics and beta-blockers did not change significantly. CONCLUSIONS: In refractory ADHF a NHMS improves significantly symptoms and renal function, with a better use of vasodilators. PMID- 20308916 TI - Sodium nitroprusside infusion prevents hypothyroidism in patients undergoing coronary artery bypass grafting: a prospective randomized clinical trial. AB - OBJECTIVE: The level of thyroid hormones is an important factor in determining the outcome of coronary artery bypass patients. Sodium nitroprusside (SNP) is a natural donor of nitric oxide which has been shown to interfere with thyroid hormone synthesis. Whether clinical use of sodium nitroprusside has any effect on thyroid function has not yet been investigated. The aim of this study was to investigate the effects of SNP administration on circulating levels of thyroid hormones. METHODS: One hundred and six consecutive patients who underwent coronary artery bypass grafting operation were prospectively randomized to receive continuous infusions of either SNP or saline limited to the rewarming time of cardiopulmonary bypass (CPB). Free triiodothyronine (T3), total T3, free thyroxine (T4), total T4 and thyroid-stimulating hormone (TSH) levels were analyzed. RESULTS: Free T3, TSH and albumin changes of SNP and control groups were statistically different from each other. In the SNP group, free T3 values stayed in the euthyroid range between CPB and post-CPB periods, the period when SNP was infused, whereas it continued to decline to hypothyroidic levels in the control group. In addition, in the SNP group, an elevation in TSH levels was observed during the CPB period. Postoperatively, an earlier restoration of free T3 and TSH levels was observed in the SNP group when compared to the control group. CONCLUSION: In this study, administration of SNP during cardiopulmonary bypass is shown to regulate free T3 and TSH levels positively. PMID- 20308917 TI - Influences of thiopurine methyltransferase genotype and activity on thiopurine induced leukopenia in Korean patients with inflammatory bowel disease: a retrospective cohort study. AB - BACKGROUND AND AIM: Myelotoxicity has been shown to be very common in Korean patients with inflammatory bowel disease (IBD) during azathioprine (AZA) or 6 mercaptopurine (6-MP) treatment. The purpose of this study was to investigate the relative risk of the thiopurine methyltransferase (TPMT) and inosine triphosphate pyrophosphatase (ITPA) genotypes and TPMT activity for the development of leukopenia in Korean IBD patients during AZA/6-MP treatment. METHODS: We retrospectively analyzed 286 Korean patients with IBD who had been treated with AZA/6-MP for at least 6 months between June 1996 and September 2006. Common TPMT mutations, including TPMT*1, *2, *3A, *3B, and *3C, and ITPA mutations, including 94C>A and IVS2+21A>C, were determined using a high-performance liquid chromatography method. TPMT activity was measured using liquid chromatography with coupled mass spectrometry/mass spectrometry. RESULTS: Leukopenia occurred in 118 cases (41.3%). TPMT *1/*3C was detected in 7 cases (2.4%), and ITPA 94 C>A was detected in 66 cases (23.1%), including 63 heterozygotes (22.1%) and 3 homozygotes (1.0%). The median TPMT activity was 9.3 U/mL (interquartile range 10.4, range 2.1 to 76.2). Cox regression analysis revealed that patients with heterozygous *3C type TPMT had a higher probability of leukopenia than those with wild type TPMT (P=0.02). Patients with intermediate TPMT activity had a lower probability of leukopenia than those with low activity (P=0.01). However, the ITPA genotype did not affect the risk of leukopenia. CONCLUSIONS: Our data showed that it could be helpful to examine TPMT genotypes and to measure TPMT activity in Korean patients taking AZA/6-MP to predict the development of leukopenia. PMID- 20308918 TI - Sclerotherapy in a child using the transnasal route. PMID- 20308919 TI - Sequential or concomitant therapy for Helicobacter pylori eradication? PMID- 20308920 TI - Deleterious combined effects of salt-loading and endothelial cell restricted endothelin-1 overexpression on blood pressure and vascular function in mice. AB - BACKGROUND: We previously showed that young transgenic mice overexpressing preproendothelin-1 specifically in endothelial cells had hypertrophic remodeling, endothelial dysfunction, increased vascular NADPH oxidase activity, and inflammation in mesenteric small arteries without blood pressure (BP) elevation compared to nontransgenic wild-type littermates. To assess the consequences of salt-loading and the role of endothelin receptors, we investigated the effects of these on vascular structure, function, and oxidative stress in mesenteric arteries in salt-loaded transgenic mice treated with endothelin receptor antagonists. METHODS: Ten-month-old male transgenic and wild-type littermates were salt-loaded (4% NaCl) and treated with endothelin subtype A receptor antagonist (ET(A)RA, ABT-627, 5 mg/kg per day), endothelin subtype B receptor antagonist (ET(B)RA; A-192621, 30 mg/kg per day), or ET(A)/BRA (bosentan, 100 mg/kg per day) for 4 weeks. BP was measured by radiotelemetry, vascular reactivity of mesenteric small arteries was studied on a pressurized myograph, and vascular NADPH oxidase activity was studied by lucigenin chemiluminescence. RESULTS: Transgenic+salt mice had significantly increased BP compared with wild type+salt mice, which was prevented by ET(A)RA and dual ET(A/B)RA but further increased by ETB antagonism. Increased small artery media/lumen ratio of transgenic+salt mice was significantly decreased only by dual ET(A/B)RA (P < 0.01), whereas no differences were found in media cross-sectional area. Impaired maximal relaxation of small arteries to acetylcholine was significantly prevented with ET(A)RA and ET(A/B)RA (P < 0.05). N(omega)-nitro-L-arginine methyl ester induced reduction of acetylcholine maximal relaxation was partially prevented by ET(A)RA, completely prevented by dual, and partially restored by vitamin C preincubation following dual ET(A/B)RA. The blunted endothelin-1 contractile response of small arteries found in transgenic+salt mice was partially restored by ET(A)RA and completely prevented by dual ET(A/B)R antagonism. The vasoconstrictor response to endothelin-1 was not altered in the presence or absence of ET(B)RA. Increased vascular NADPH oxidase activity of transgenic+salt mice was further increased by ET(B)RA but returned to levels seen in wild type+salt mice under either ET(A)RA and ET(A/B)RA. CONCLUSION: Transgenic+salt mice with endothelin-1 overexpression have structural alterations of mesenteric resistance vessels, endothelial dysfunction due to reduced nitric oxide bioavailability, a reduced responsiveness to endothelin-1, and enhanced vascular NADPH oxidase activity. ET(B)RA further exacerbated these effects, whereas ET(A)RA significantly improved but did not normalize them in chronically salt loaded transgenic mice with endothelial cell human endothelin-1 overexpression. Salt and endothelin-1 overexpression have deleterious additive effects on vascular remodeling mediated by ET(A)R and ET(B)R. ET(B)R probably located in the endothelium, however, also exerts beneficial effects on endothelial function in this experimental paradigm. The present study provides the first in-vivo demonstration that endothelin-1 overexpression when associated with high-salt intake results in enhanced endothelial dysfunction and vascular remodeling of resistance vessels, and contributes to elevated BP, via ET(A)R and ET(B)R. PMID- 20308921 TI - Hypertensive effects of central angiotensin II infusion and restraint stress are reduced with age. AB - OBJECTIVE: We investigated the effect of age on cardiovascular responses mediated by central angiotensin II (AngII) after intracerebroventricular infusion of AngII, and during restraint stress. METHODS: Blood pressure (BP) and heart rate (HR) of young (5-month-old) and old (27-month-old) male Fischer-344 x Brown Norway rats were measured using radiotelemetry. AngII was infused intracerebroventricularly using osmotic minipumps (10 ng/0.5 microl/h for 11 days). BP and HR responses to stress were evaluated by placing animals in restrainers for 20 min before and after intracerebroventricular infusion of the AngII-type-1 receptor inhibitor losartan (15 microg/microl per h for 3 days). RESULTS: Resting BP was significantly elevated and HR was significantly lower in old rats compared with young. AngII-induced BP increase was markedly reduced in old rats, but HR responses were similar. Diurnal variation of both BP and HR was lower in old animals, and AngII reduced the amplitude of BP variation in young rats, but not in old. Restraint stress-induced BP and HR elevations were reduced with age. BP responses were diminished by central losartan infusion in both young and old, but this effect was more significant in young rats. In addition, expression of CuZn-superoxide dismutase and catalase declined significantly with age in the hypothalamus, whereas baseline oxidative stress increased. In contrast, AngII-induced increase in hypothalamic oxidative stress decreased with age. CONCLUSION: This study demonstrates that the role of central AngII diminishes with age in the regulation of BP both during baseline conditions and during stress, whereas the involvement of AngII in the regulation of HR remains unaffected. PMID- 20308922 TI - Impact of different definitions of the metabolic syndrome on the prevalence of organ damage, cardiometabolic risk and cardiovascular events. AB - OBJECTIVES: We compared definitions of metabolic syndrome performed by ATPIII [the National Cholesterol Education Program Adult Treatment Panel III; three criteria of the following: systolic blood pressure >or=130 mmHg and/or diastolic blood pressure >or=85 mmHg, fasting serum glucose >or=110 mg/dl, high-density lipoprotein plasma cholesterol or=150 mg/dl, waist circumference >or=102 cm (men) or 88 cm (women)], AHA (the American Heart Association; same cut-off of ATPIII except serum glucose >or= 100 mg/dl) and IDF [the International Diabetes Federation; mandatory criteria of visceral obesity with reduced cut-off of 94 cm (men) or 80 cm (women), and at least two criteria with the same cut-off as in AHA] for their impact on metabolic syndrome prevalence, cardiac organ damage, long-term risk of cardiovascular events and death for any cause and risk of developing diabetes mellitus, in-office and out-of-office hypertension and left ventricular hypertrophy (LVH). METHODS: In 2051 participants, we measured office, home and ambulatory blood pressure as well as metabolic, anthropometric and echocardiographic variables. Measurements were performed between 1990 and 1992 and repeated 10 years later. Information on long-term incidence of cardiovascular events and all-cause deaths was also collected. RESULTS: Prevalence of metabolic syndrome was significantly greater when using the AHA and IDF as compared to the ATPIII definition. Prevalence of LVH was higher in participants with than without metabolic syndrome and similar for the three definitions. Over 12-year follow-up, there were 179 cardiovascular events and 233 deaths for any cause. The risk of cardiovascular events and death was markedly greater for participants with as compared with those without metabolic syndrome, regardless of the definition of metabolic syndrome. This was the case also for the risk of new-onset diabetes mellitus, office, home and ambulatory hypertension and new-onset LVH. CONCLUSION: Risks of fatal and nonfatal cardiovascular events, diabetes mellitus, hypertension and LVH were similar for the three definitions of metabolic syndrome. However, the AHA and IDF definitions are more sensitive than that of ATPIII in identifying metabolic syndrome condition. PMID- 20308923 TI - Genu recurvatum in cerebral palsy--part B: hamstrings are abnormally long in children with cerebral palsy showing knee recurvatum. AB - Hyperextension of the knee in stance (knee recurvatum) is a common disorder in patients with spastic cerebral palsy (CP). A group 35 children with CP (47 lower limbs) was divided into two subgroups according to the timing of maximum knee extension during the stance phase of gait. Gait analysis and musculoskeletal modelling data were compared with a control group of 12 normally developing children. We observed no difference in kinematics between the CP groups who showed an equinus position of the foot at initial contact. Both groups showed increased external extensor moments across the knee. The muscle-tendon lengths of the hamstrings were abnormally long at initial contact, and in both recurvatum groups, contracted faster compared with the control group. Surface electromyography revealed prolonged activity of the hamstrings in stance and early activation in swing. Abnormally long hamstrings at initial contact together with equinus position of the foot are the main causes of genu recurvatum in children with CP. PMID- 20308924 TI - Reduced bone mass accrual in swim-trained prepubertal mice. AB - INTRODUCTION: Clinical studies have found that nonimpact non-weight-bearing sports are associated with normal to low bone mineral densities. The objective of this study was to quantify structural bone adaptations of the mouse to swimming using in vivo micro-computed tomography. METHODS: Prepubertal female mice underwent a 16-wk training program, in which they swam for progressively increasing durations up to 55 min for 5 d.wk(-1). A sham group was subjected to the water, but they did not perform the swimming exercise. Skeletal sites that were assessed included the proximal humerus, lumbar spine, midshaft and distal femur, proximal tibia, and the skull. RESULTS: Normal bone mass accrual was suppressed in the swim group during the initial 4 wk of training, during rapid growth. Swim mice gained 31.8% less (P = 0.001) and 16.7% less (P = 0.003) trabecular bone volume at the proximal tibial and humeral metaphyses, respectively. In the 12 wk that followed, low trabecular bone volume persisted in the swimmers (P < 0.001). Trabecular properties were reduced primarily at the metaphysis but not the epiphysis, and cortical bone was reduced at both compartments. At the femoral midshaft, swim mice had less cortical porosity (SHAM = 32% +/- 3% vs SWIM = 22% +/- 3%, P = 0.043). Despite the bone microarchitectural adaptations, swimming did not induce detectable changes to macroarchitecture, including bone length and total volume. Tissue mineral density was unaffected by swimming, suggesting that material changes did not occur. CONCLUSIONS: In conclusion, the response of prepubertal mice to swimming was adaptation at the bone microarchitectural level and resulted in an altered topology that was sustained until the end of the training program. Low bone mass was systemic throughout the mouse, with the largest depressions in the hindlimbs and spine. PMID- 20308925 TI - Relation of femoral diameter, shear rate, and dilatory response to knee extensor exercise. AB - INTRODUCTION: Younger women typically exhibit marked dilation of the common femoral artery (CFA) during knee extensor exercise; this is in apparent contrast to subject groups with larger (men) and/or older (older women) vessels, which on average display much smaller exercise-induced increases in CFA diameter. To gain additional insight into this variation, the present study closely examined within and between-group relationships among CFA diameter, shear rate, and the magnitude of exercise-induced CFA dilation. METHODS: Healthy women (15 younger and 18 older) and men (15 younger and 13 older) performed graded single-leg knee extensor exercise while CFA diameter and blood velocity were measured using Doppler ultrasound. RESULTS: Resting CFA diameter was smaller (P < 0.05) in women (younger: 0.71 +/- 0.02 cm; older: 0.72 +/- 0.02 cm) compared with men (younger: 0.84 +/- 0.01 cm; older: 0.97 +/- 0.03 cm). Resting CFA diameter was inversely associated with peak shear rate (combined groups: r = -0.83, P < 0.001) and the magnitude of dilation in women (younger: r = -0.82; older: r = -0.73, P < 0.001) and younger men (r = -0.66, P < 0.01) but not in older men (r = -0.17, P = 0.56). The dilatory response of the CFA to graded increases in shear rate showed a continuum across groups best described by a quadratic function (r2 = 0.89). Using piecewise regression modeling, a threshold diameter of 0.79 cm was identified below which diameter is inversely related to the magnitude of CFA dilation but above which little to no dilation was present. CONCLUSIONS: The CFA dilates to knee extensor exercise in women and men, the magnitude of which varies because of differences in shear rate across CFA diameters. PMID- 20308926 TI - Mechanisms for increases in VO2max with endurance training in older and young women. AB - PURPOSE: To examine the time course and mechanisms of cardiorespiratory fitness adaptation to training in older (O) and young (Y) women. METHODS: A total of six O (69 +/- 7 yr) and eight Y (25 +/- 5 yr) women were examined before training and after 3, 6, 9, and 12 wk of training. Training was performed on a cycle ergometer three times per week for 45 min at ~70% of VO2max. RESULTS: VO2max (mL.kg( 1).min(-1)) increased within 3 wk, with further changes observed at weeks 6 and 9 in both O (17% +/- 14%) and Y and also posttraining (12 wk) in Y (22% +/- 6%, P < 0.05). Maximal cardiac output (Qmax, open-circuit acetylene) and stroke volume increased only in Y after 9 wk of training (P < 0.05). Age * testing time interactions in maximal arterial-venous O2 difference (a-vO2diff) after 6 wk of training revealed a greater dependence on a-vO2diff in O compared with Y (P < 0.05); ~65% of the change in VO2max from pretraining to posttraining was explained by a widened maximal a-vO2diff in O compared with almost equal increases in Qmax and maximal a-vO2diff in Y. The early adaptations (first 3 wk) in O relied exclusively on a nonsignificant increase in Qmax, whereas Y depended on a widened maximal a-vO2diff. Later changes in VO2max were explained exclusively by an improved maximal a-vO2diff in O and a larger Qmax in Y. CONCLUSIONS: O and Y women displayed a different time course of training adaptation in VO2max, with Y (after an initial improvement in maximal a-vO2diff) depending more on changes in Qmax and O mostly relying on a widened maximal a vO2diff. PMID- 20308927 TI - Inhaled fluticasone and the hormonal and inflammatory response to brief exercise. AB - PURPOSE: Inhaled corticosteroids (ICS) improve symptoms in lung diseases, such as asthma. Initial data suggest that the effects of ICS remain localized in the lung; however, recent studies demonstrate alteration to the peripheral immune system in patients with asthma. We sought to evaluate the effect of ICS on peripheral immune mediators and hypothalamic-pituitary-adrenal axis and their response to exercise in healthy men. METHODS: Eleven healthy males (18-30 yr old) were placed on 2 wk of fluticasone proprionate (440 MUg) twice daily. A 30-min bout of exercise was performed on a cycle ergometer at approximately 70% of peak work rate before and after the start of ICS. Blood was sampled before and after exercise. Cytokines and hypothalamic-pituitary-adrenal axis mediators were measured by ELISA, and fluticasone was measured by liquid chromatography/tandem mass spectrometry. RESULTS: After ICS treatment, cortisol and adrenocorticotropin were decreased, and a blunted exercise response was observed for cortisol, adrenocorticotropin, and growth hormone. Peripheral leukocytes and neutrophils were significantly increased in response to exercise in both the untreated and the ICS-treated conditions and at baseline after ICS treatment. Interleukin-6 was elevated with ICS treatment, but the exercise response was blunted. Circulating median fluticasone levels were 0.15 ng.mL(-1) and were increased to 0.20 ng.mL( 1) in response to exercise. CONCLUSIONS: Exercise revealed deficits in growth hormone production after ICS treatment not identified by static markers. Neutrophils were shown to be surrogate markers of the systemic effect of ICS. Exercise significantly increased circulating levels of fluticasone. Exercise challenge tests can be used to assess the physiological effect of exogenous corticosteroids. PMID- 20308928 TI - External and internal biphasic direct current shock doses for pediatric ventricular fibrillation and pulseless ventricular tachycardia. AB - OBJECTIVE: To determine energy dose and number of biphasic direct current shocks for pediatric ventricular fibrillation (VF) and pulseless ventricular tachycardia (VT). DESIGN: Observation of preshock and postshock rhythms, energy doses, and number of shocks. SETTING: Pediatric hospital. PATIENTS: Shockable ventricular dysrhythmias. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Forty-eight patients with VF or pulseless VT received external shock at 1.7 +/- 0.8 (mean +/- SD) J/kg. Return of spontaneous circulation (ROSC) occurred in 23 (48%) patients with 2.0 +/- 1.0 J/kg, but 25 (52%) patients remained in VF after 1.5 +/- 0.7 J/kg (p = .05). In 24 non-responding patients, additional 1-8 shocks (final dose, 2.8 +/- 1.2 J/kg) achieved ROSC in 14 (58%) with 2.6 +/- 1.1 J/kg but not in 10 (42%) with 3.2 +/- 1.2 J/kg (not significant). Overall, 37 (77%) patients achieved ROSC with 2.2 +/- 1.1 J/kg (range, 0.5-5.0 J/kg). Eight patients without ROSC recovered with cardiopulmonary bypass and internal direct current shock. At 13 subsequent episodes of VF or VT among eight patients, five achieved ROSC and survived. In combined first and subsequent resuscitative episodes, doses in the range of 2.5 to < 3 J/kg achieved most cases of ROSC. Survival for > 1 yr was seen in 28 (78%) of 36 patients with VF and seven (58%) of 11 patients with VT, with 35 (73%) overall. Lack of ROSC was associated with multiple shocks (p = .003). Repeated shocks with adhesive pads had significantly less impedance (p < .001). Pads in an anteroposterior position achieved highest ROSC rate. Internal shock for another 48 patients with VF or VT achieved ROSC in 28 (58%) patients with 0.7 +/- 0.4 J/kg but not in 20 patients with 0.4 +/- 0.3 J/kg (p = .01). Nineteen of the nonresponders who received additional internal 1-9 shocks at 0.6 +/- 0.5 J/kg and one patient given extracorporeal membrane oxygenation all recovered, yielding 100% ROSC, but 1-yr survival tallied 43 (90%) patients. CONCLUSIONS: The initial biphasic direct current external shock dose of 2 J/kg for VF or pulseless VT is inadequate. Appropriate doses for initial and subsequent shocks seem to be in the range of 3-5 J/kg. Multiple shocks do not favor ROSC. The dose for internal shock is 0.6-0.7 J/kg. PMID- 20308930 TI - Brain tumor resection in children: neurointensive care unit course and resource utilization. AB - OBJECTIVE: To describe the pediatric intensive care unit (PICU) course and resource utilization for children with brain tumor resection and to identify factors predicting prolonged (>1 day) PICU length of stay. After craniotomy for brain tumor resection, children recover in the PICU. A few require critical care interventions and a >24-hr length of stay. DESIGN: We reviewed all brain tumor resection patients admitted to the PICU over 2 yrs. Preoperative, intraoperative, and postoperative variables and tumor characteristics were examined. The extracted variables were compared between two groups with a length of stay in the PICU of >1 or <1 day. SETTING: Pediatric intensive care unit in a tertiary academic children's medical center. PATIENTS: A total of 105 patients post brain tumor resection were admitted to the PICU over the study period and analyzed. INTERVENTIONS: Record review. MEASUREMENTS AND MAIN RESULTS: Thirty-two (31%) of 105 patients remained in the PICU for >1 day. The mean age of patients in the >1 day group was 5.0 +/- 0.81 yrs and 8.78 +/- 0.65 yrs in the <1 day group (p < .05). The estimated blood loss was 20 +/- 2.37 mL/kg in the >1 day and 9 +/- 0.92 mL/kg in the <1 day group (p < .05). Fifteen (14.3%) patients were mechanically ventilated on arrival in the PICU; these patients more often had a length of stay of >1 day (p < .05). The number of unexpected intensive care unit interventions were 0.7 per patient, were more common in the >1 day group, and included treatment of sodium abnormalities, new neurologic deficits, paresis, or seizures (p < .05). In a logistic regression model, estimated blood loss and intubation on arrival predicted longer lengths of stay in the PICU (odds ratio, 1.1; 95% confidence interval, 1.05-1.18; and odds ratio, 33; 95% confidence interval, 2.57 333, respectively), with a receiver operating characteristic curve of 0.86 and 95% confidence interval, 0.78-0.94. CONCLUSIONS: Large intraoperative estimated blood loss and intubation on arrival may be predictive of PICU lengths of stay of >1 day for children who have had a craniotomy for brain tumor resection. Intensive care unit interventions are more common in these children. PMID- 20308929 TI - Critical illness in children with influenza A/pH1N1 2009 infection in Canada. AB - OBJECTIVE: To describe characteristics, treatment, and outcomes of critically ill children with influenza A/pandemic influenza A virus (pH1N1) infection in Canada. DESIGN: An observational study of critically ill children with influenza A/pH1N1 infection in pediatric intensive care units (PICUs). SETTING: Nine Canadian PICUs. PATIENTS: A total of 57 patients admitted to PICUs between April 16, 2009 and August 15, 2009. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Characteristics of critically ill children with influenza A/pH1N1 infection were recorded. Confirmed intensive care unit cases were compared with a national surveillance database containing all hospitalized pediatric patients with influenza A/pH1N1 infection. Risk factors were assessed with a Cox proportional hazard model. The PICU cohort and national surveillance data were compared, using chi-square tests. Fifty-seven children were admitted to the PICU for community acquired influenza A/pH1N1 infection. One or more chronic comorbid illnesses were observed in 70.2% of patients, and 24.6% of patients were aboriginal. Mechanical ventilation was used in 68% of children, 20 children (35.1%) had acute lung injury on the first day of admission, and the median duration of ventilation was 6 days (range, 0-67 days). The PICU mortality rate was 7% (4 of 57 patients). When compared with nonintensive care unit hospitalized children, PICU children were more likely to have a chronic medical condition (relative risk, 1.73); aboriginal ethnicity was not a risk factor of intensive care unit admission. CONCLUSIONS: During the first outbreak of influenza A/pH1N1 infection, when the population was naive to this novel virus, severe illness was common among children with underlying chronic conditions and aboriginal children. Influenza A/pH1N1-related critical illness in children was associated with severe hypoxemic respiratory failure and prolonged mechanical ventilation. However, this higher rate and severity of respiratory illness did not result in an increased mortality when compared with seasonal influenza. PMID- 20308931 TI - Reducing catheter-associated bloodstream infections in the pediatric intensive care unit: Business case for quality improvement. AB - OBJECTIVE: To determine whether catheter-associated bloodstream infections were associated with increased lengths of stay in pediatric intensive care units and hospitals and increased healthcare costs in critically ill children. Previous studies have shown that hospital-acquired bloodstream infections are associated with longer stays in pediatric intensive care units, increased hospital costs, and increased hospital mortality. Catheter-associated bloodstream infections comprise the vast majority of hospital-acquired bloodstream infections. DESIGN: Retrospective, case-matched, cohort study and financial analysis. SETTING: University-affiliated children's medical center. PATIENTS: Twenty-two critically ill children with catheter-associated bloodstream infections and their matched controls. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We compared the length of stay, mortality, and hospital costs in critically ill children with catheter-associated bloodstream infections and matched controls. The presence of catheter-associated bloodstream infections extended the entire hospital length of stay by 9 days (6.5 days while in the pediatric intensive care unit) and increased hospital costs by $33,039, primarily driven by the increase in length of stay days. Quality improvement efforts directed at reducing the prevalence of catheter-associated bloodstream infections during the period of study decreased total hospital days by 354, reduced total hospital costs by $1,298,271, and reduced total costs to payers by $1,415,676. CONCLUSION: The potential cost savings from reducing or eliminating catheter-associated bloodstream infections in the pediatric intensive care unit are significant. Elimination of catheter associated bloodstream infections will directly reduce hospital costs, improve asset utilization, and most importantly, improve clinical care. PMID- 20308932 TI - Prevalence of adverse events in pediatric intensive care units in the United States. AB - OBJECTIVES: Selection of relevant patient safety interventions for the pediatric intensive care (PICU) requires identification of the types and severity of adverse events (AEs) and adverse drug events (ADEs) that occur in this setting. The study's objectives were to: 1) determine the rates of AEs/ADEs, including types, severity, and preventability, in PICU patients; 2) identify population characteristics associated with increased risk of AEs/ADEs; 3) develop and test a PICU specific trigger tool to facilitate identification of AEs/ADEs. DESIGN, SETTING, PATIENTS: Retrospective, cross-sectional, randomized review of 734 patient records who were discharged from 15 U.S. PICUs between September and December 2005. INTERVENTION: A novel PICU-focused trigger tool for AE/ADE detection. MEASUREMENTS AND RESULTS: Sixty-two percent of PICU patients had at least one AE. A total of 1488 AEs, including 256 ADEs, were identified. This translates to a rate of 28.6 AEs and 4.9 ADEs per 100 patient-days. The most common types of AEs were catheter complications, uncontrolled pain, and endotracheal tube malposition. Ten percent of AEs were classified as life threatening or permanent; 45% were deemed preventable. Higher adjusted rates of AEs were found in surgical patients (p = .02), patients intubated at some point during their PICU stay (p = .002), and patients who died (p < .001). Surgical patients had higher preventable adjusted AE (p = .01) and ADE rates (p = .02). The adjusted cumulative risk of an AE per PICU day was 5.3% and 1.6% for an ADE alone. There was a 4% increase in adjusted ADEs rates for every year increase in age. CONCLUSIONS: AEs and ADEs occur frequently in the PICU setting. These data provide areas of focus for evidence-based prevention strategies to decrease the substantial risk to this vulnerable pediatric population. PMID- 20308933 TI - Predictive factors for the outcome of noninvasive ventilation in pediatric acute respiratory failure. AB - OBJECTIVES: To identify success and failure prognostic signs of noninvasive ventilation in pediatric acute respiratory failure. Noninvasive ventilation constitutes an alternative treatment for pediatric acute respiratory failure. However, tracheal intubation should not be delayed when considered necessary. DESIGN: Prospective, noncontrolled, clinical study. SETTING: Pediatric intensive care unit in a university hospital. PATIENTS: Children (age range, 1 month-16 yrs) with moderate-to-severe acute respiratory failure who received noninvasive ventilation during a 4-year period. Failure was defined as the need for tracheal intubation. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Nine (19.1%) of 47 patients needed tracheal intubation between the third and 87th hour after the start of treatment (33.6 +/- 29.6 hrs). Failure was associated with the younger age group (4 +/- 3.3 yrs vs. 7.7 +/- 5 yrs, p < .04), acute respiratory distress syndrome (failure/acute respiratory distress syndrome: 5 of 10 vs. failure/non acute respiratory distress syndrome: 4 of 37, p = .013), and worsening radiographic images taken at 24 hrs and/or 48-72 hrs (p = .001 and p < .001, respectively). A significant reduction in heart rate was observed between the second and fourth hour after starting noninvasive ventilation (130 +/- 25.8 bpm vs. 116 +/- 27.7 bpm, p < .001) and Pco2 (54.1 +/- 19.5 torr vs. 48.6 +/- 14.3 torr; 7.21 +/- 2.6 vs. 6.48 +/- 1.91 kPa, p < .007) in the success group. The failure group had a higher rate of breathing assistance, both initial and maximal. In the multivariant analysis, only maximum mean airway pressure and Fio2 formed part of the success/failure discriminant function with a cutoff point of 11.5 and 0.57, respectively. CONCLUSIONS: Modifications in a patient's respiratory assistance were made depending on the clinical, blood gas, and radiologic evolution of the patient. Mean airway pressure and Fio2 values of >11.5 and 0.6, respectively, predict failure and possibly set the limit above the patient's risk of delayed intubation increases. PMID- 20308934 TI - Mumps outbreak in the Republic of Moldova, 2007-2008. AB - BACKGROUND: Moldova experienced a nationwide mumps outbreak between 2007 and 2008. Single-dose monovalent mumps vaccination at 15 to 18 months was introduced in 1983, replaced by a 2-dose MMR schedule at age 1 and 6 to 7 years in 2002. We investigated the outbreak to quantify its extent, explore the role of primary and secondary vaccine failure, and provide control recommendations. METHODS: We analyzed national mumps surveillance and vaccination coverage data to estimate vaccine effectiveness (VE) using the screening method. A retrospective cohort study in 5 educational institutions was conducted to determine age-specific attack rates (ARs) and VE. We compared vaccine strain-specific ARs. Isolation and genotyping of mumps virus strains were performed. RESULTS: Of 31,142 cases reported during October 2007 and July 2008, 80% were in 15- to 24-year-olds. Of cases with information (66%), 92% were vaccinated once, 4% twice. One-dose mumps VE estimates based on surveillance data over 1997-2001 declined from 91% (95% CI: 88%-92%) in 2-year-olds to 72% (70%-74%) in 15- to 19-year-olds. In the cohort study (n = 1589), VE was -40% (-120% to 20%) for 1 dose. For 2 doses it was 62% ( 43% to 90%) in 13- to 15-year-olds. ARs were higher in individuals vaccinated with Urabe strains (43%) than with Leningrad-Zagreb strains (14%, P < 0.001). Mumps virus genotype G5 was identified. CONCLUSIONS: Low effectiveness of single dose mumps vaccination was the main cause of the outbreak. Waning immunity may have contributed to this. The risk of mumps in 2-dose vaccinees was low. Other countries in which large population groups have received <2 doses of mumps vaccine may face similar outbreaks. PMID- 20308935 TI - Parental attitudes about influenza immunization and school-based immunization for school-aged children. AB - OBJECTIVES: Identify parental beliefs and barriers related to influenza immunization of school-aged children and acceptance of school-based influenza immunization. METHODS: We conducted a cross-sectional survey of parents of elementary school-aged children in November 2008. Outcomes were receipt of influenza vaccine, acceptance of school-based immunization, and barriers to immunization. RESULTS: Response rate was 65% (259/397). Parents reported that 26% of children had received the vaccine and 24% intended receipt. A total of 50% did not plan to immunize. Factors associated with receipt were belief that immunization is a social norm (adjusted odds ratios [AOR], 10.8; 95% CI, 2.8 41.8), belief in benefit (AOR, 7.8; CI, 1.8-33.8), discussion with a doctor (AOR, 7.0; CI, 2.9-16.8), and belief that vaccine is safe (AOR, 4.0; CI, 1.0-15.8). A total of 75% of parents would immunize their children at school if the vaccine were free, including 59% (76/129) who did not plan to immunize. Factors associated with acceptance of school-based immunization were belief in benefit (AOR, 6.1; 95% CI, 2.7-14.0), endorsement of medical setting barriers (AOR, 3.7; 95% CI, 1.3-10.3), and beliefs that immunization is a social norm (AOR, 3.3; 95% CI, 1.4-7.6) and that the child is susceptible to influenza (AOR, 2.6; 95% CI, 1.2-5.7). Medical setting barriers were competing time demands, inconvenience, and cost; school barriers were parents' desire to be with children and competence of person delivering the vaccine. CONCLUSIONS: School-based immunization programs can increase immunization coverage by targeting parents for whom time demands and inconvenience are barriers, demonstrating that immunization is a social norm, and addressing concerns about influenza vaccine benefit and safety. PMID- 20308937 TI - Newborn serum retinoic acid level is associated with variants of genes in the retinol metabolism pathway. AB - Retinoic acid (RA) is a critical regulator of gene expression during embryonic development. In rodents, moderate maternal vitamin A deficiency leads to subtle morphogenetic defects and inactivation of RA pathway genes causes major disturbances of embryogenesis. In this study, we quantified RA in umbilical cord blood of 145 healthy full-term Caucasian infants from Montreal. Sixty seven percent of values were <10 nmol/L (84 were <0.07 nmol/L) and 33% had moderate or high levels. Variation in RA could not be explained by parallel variation in its precursor, retinol (ROL). However, we found that the (A) allele of the rs12591551 single nucleotide polymorphism (SNP) in the ALDH1A2 gene (ALDH1A2rs12591551(A)), occurring in 19% of newborns, was associated with 2.5-fold higher serum RA levels. ALDH1A2 encodes retinaldehyde dehydrogenase (RALDH) 2, which synthesizes RA in fetal tissues. We also found that homozygosity for the (A) allele of the rs12724719 SNP in the CRABP2 gene (CRABP2rs12724719(A/A)) was associated with 4.4 fold increase in umbilical cord serum RA. CRABP2 facilitates RA binding to its cognate receptor complex and transfer to the nucleus. We hypothesize that individual variation in RA pathway genes may account for subtle variations in RA dependent human embryogenesis. PMID- 20308936 TI - Persistence of adenovirus nucleic acids in nasopharyngeal secretions: a diagnostic conundrum. AB - BACKGROUND: Polymerase chain reaction (PCR) assays increase the rate of viral detection in clinical specimens, compared with conventional virologic methods. Studies suggest that PCR may detect virus nucleic acid (NA) that persists in the respiratory tract. METHODS: We analyzed virologic data from children having frequent upper respiratory infections (URI), who were followed up in a longitudinal study. Nasopharyngeal secretions were collected at URI onset and when acute otitis media was diagnosed; virus studies were performed using conventional diagnostics and PCR. Repeated presence of adenovirus by PCR was further studied by sequencing and phylogenetic analysis. RESULTS: Of 581 URI episodes in 76 children, 510 viruses were detected. Of the viruses detected by PCR, 15% were those detected previously; repeated positives occurred most frequently with adenovirus. Sequencing results were available in 13 children with repeated adenovirus detection; the following 4 patterns of infection were identified (16 instances): (1) adenovirus of the same serotype and strain detected continuously (n = 8 instances), (2) adenovirus of different serotypes detected during sequential URI episodes (n = 3), (3) adenovirus of the same serotype but different strains detected during sequential URI episodes (n = 3), and (4) adenovirus of the same serotype and strain detected intermittently (n = 2). CONCLUSIONS: Among children with frequent URIs, repeated positive PCR results for adenovirus NA may represent a new serotype/strain, or persistence of viral NA. Results must be interpreted with caution; clinical correlation and presence of other viruses are important. Further longitudinal studies of children during and after infection are required for better understanding of the clinical significance of positive PCR tests for adenovirus NA in the respiratory tract. PMID- 20308938 TI - Dual-platform proteomics study of plasma biomarkers in pediatric patients undergoing cardiopulmonary bypass. AB - Plasma samples from pediatric cardiac patients undergoing cardiopulmonary bypass (CPB) procedures were used to identify and characterize patterns of changes in potential biomarkers related to tissue damage and inflammation. These included proteins associated with systemic inflammatory response syndrome. Potential biomarkers were identified using a dual-platform proteomics approach requiring approximately 150 microL of plasma, which included two-dimensional difference gel electrophoresis (2D-DIGE) and a multiplexed immunoassay. Methods used in the dual approach measured levels of 129 proteins in plasma from pediatric CPB patients. Of these, 70 proteins changed significantly (p<0.05) between time points, and 36 of these retained significance after the highly stringent Bonferroni correction [p<0.001 for 2D-DIGE and p<0.00056 for multianalyte profile (MAP) assays]. Many of the changing proteins were associated with tissue damage, inflammation, and oxidative stress. This study uses a novel approach that combines two discovery proteomics techniques to identify a pattern of potential biomarkers changing after CPB. This approach required only 150 microL of plasma per time point and provided quantitative information on 129 proteins. The changes in levels of expression of these proteins may provide insight into the understanding, treatment, and prevention of systemic inflammation, thereby helping to improve the outcomes of pediatric CPB patients. PMID- 20308939 TI - Early isomerization of bilirubin in phototherapy of neonatal jaundice. AB - Neonatal jaundice is usually treated with phototherapy that converts bilirubin to more polar stereoisomers. These should theoretically be less able to cross the blood-brain barrier. The rates of photoisomer formation and concentrations accumulating in the circulation may have a bearing on the risk of kernicterus. The purpose of this study was to determine the rate of appearance of the major 4Z, 15E photoisomer of bilirubin during the early stages of phototherapy. Twenty jaundiced neonates were treated with phototherapy, and blood samples were drawn before and at approximately 15, 30, 60, and 120 min (10 infants) or at approximately 15, 60, 120, and 240 min (10 infants) after beginning phototherapy. Blood samples were analyzed for total serum bilirubin (TSB) and the 4Z, 15E photoisomer of bilirubin. Significant (p<0.0001) formation of the 4Z, 15E photoisomer was detectable within 15 min. The change in TSB from time 0 was insignificant at 120 min but reached significance at 240 min (p<0.001). The 4Z, 15E bilirubin constituted up to 20-25% of TSB at 2 h and may not have peaked by 4 h. Further studies are needed to determine whether this early shift in balance between bilirubin isomers with different polarities may impact the risk of bilirubin encephalopathy even before TSB starts to fall. PMID- 20308940 TI - Noninvasive respiratory support of juvenile rabbits by high-amplitude bubble continuous positive airway pressure. AB - Bubble continuous positive airway pressure (B-CPAP) applies small-amplitude, high frequency oscillations in airway pressure (DeltaPaw) that may improve gas exchange in infants with respiratory disease. We developed a device, high amplitude B-CPAP (HAB-CPAP), which provides greater DeltaPaw than B-CPAP provides. We studied the effects of different operational parameters on DeltaPaw and volumes of gas delivered to a mechanical infant lung model. In vivo studies tested the hypothesis that HAB-CPAP provides noninvasive respiratory support greater than that provided by B-CPAP. Lavaged juvenile rabbits were stabilized on ventilator nasal CPAP. The animals were then supported at the same mean airway pressure, bias flow, and fraction of inspired oxygen (FiO2) required for stabilization, whereas the bubbler angle was varied in a randomized crossover design at exit angles, relative to vertical, of 0 (HAB-CPAP0; equivalent to conventional B-CPAP), 90 (HAB-CPAP90), and 135 degrees (HAB-CPAP135). Arterial blood gases and pressure-rate product (PRP) were measured after 15 min at each bubbler angle. Pao2 levels were higher (p<0.007) with HAB-CPAP135 than with conventional B-CPAP. PaCO2 levels did not differ (p=0.073) among the three bubbler configurations. PRP with HAB-CPAP135 were half of the PRP with HAB-CPAP0 or HAB-CPAP90 (p=0.001). These results indicate that HAB-CPAP135 provides greater respiratory support than conventional B-CPAP does. PMID- 20308941 TI - The effectiveness of a posted information package on the beliefs and behavior of musculoskeletal practitioners: the UK Chiropractors, Osteopaths, and Musculoskeletal Physiotherapists Low Back Pain ManagemENT (COMPLeMENT) randomized trial. AB - STUDY DESIGN: Randomized controlled trial. OBJECTIVE: To investigate the effect of a printed information package on the low back pain (LBP)-related beliefs and reported behavior of musculoskeletal practitioners (chiropractors, osteopaths, and musculoskeletal physiotherapists) across the United Kingdom. SUMMARY OF BACKGROUND DATA: A substantial proportion of musculoskeletal practitioners in United Kingdom does not follow current LBP guideline recommendations. METHODS: In total, 1758 practitioners were randomly allocated to either of the 2 study arms. One arm was posted a printed information package containing guideline recommendations for the management of LBP (n = 876) and the other received no intervention (n = 882). The primary outcome measure consisted of 3 "quality indicators" (activity, work, and bed-rest) relating to a vignette of a patient with LBP, in which responses were dichotomized into either "guideline inconsistent" or "guideline-consistent." The secondary outcome was the practitioners' LBP-related beliefs, measured using the Health Care Providers Pain and Impairment Relationship Scale. Outcomes were measured at baseline and at 6 months. RESULTS: Follow-up at 6 months was 89%. The changes in reported behavior on the quality indicators were as follows: activity, odds ratio (OR) 1.29 (95% confidence interval, 1.03-1.61) and number needed to be treated (NNT), 19 (15 28); work, OR 1.35 (1.07-1.70) and NNT 19 (14-29); and bed-rest, OR 1.31 (0.97 1.76) and NNT 47 (33-103). The composite NNT for a change from guideline inconsistent to guideline-consistent behavior on at least 1 of the 3 quality indicators was 10 (9-14). LBP-related beliefs were significantly improved in those who were sent the information package (P = 0.002), but only to a small degree (mean difference, 0.884 scale points; 95% confidence interval, 0.319 1.448). CONCLUSION: Printed educational material can shift LBP-related beliefs and reported behaviors of musculoskeletal practitioners, toward practice that is more in line with guideline recommendations. PMID- 20308942 TI - Primary intradural extramedullary melanoma of the cervical spinal cord: case report. AB - STUDY DESIGN: Case report. OBJECTIVE: We report a case of primary intradural extramedullary melanoma of the cervical spinal cord in a nonwhite patient. SUMMARY OF BACKGROUND DATA: Melanoma occurs most commonly in white populations and is rare in Asian populations. Primary malignant melanoma of the spinal cord is a rare disease entity that predominately affects the middle or lower thoracic spine. METHODS: A 39-year-old man presented with a tingling sensation in the upper extremities accompanied by motor weakness of the lower extremities. Preoperative magnetic resonance imaging (MRI) of the cervical spine suggested a multiloculated subdural hematoma in the subacute stage that spread from the level of C1 to the level of C6. RESULTS: A standard posterior midline approach was used under the impression that the subacute subdural hematoma was caused by a hidden vascular anomaly or a rare, intradural, pigmented tumor. A dark black-colored, hard, intradural mass was found, and gross total removal was performed. Histopathological investigation confirmed malignant melanoma. No hypermetabolic lesions were noted on whole-body FDG-PET. Additional dermatologic and ophthalmologic examinations did not reveal any other foci of primary melanoma. The patient was discharged with improvement of motor weakness. Subsequent radiotherapy and chemotherapy were administered. CONCLUSION: Unlike most cases of primary intradural melanoma, this patient presented with unusual radiologic findings in the cervical spinal cord. The case described in the present study illustrates that primary spinal cord melanoma is rare and must be diagnosed with caution due to its variable clinical and radiologic presentation. PMID- 20308943 TI - Evaluation of a Canadian back pain mass media campaign. AB - STUDY DESIGN: Quasi-experimental before-and-after design with control group. OBJECTIVE: We evaluated a back pain mass media campaign's impact on population back pain beliefs, work disability, and health utilization outcomes. SUMMARY OF BACKGROUND DATA: Building on previous campaigns in Australia and Scotland, a back pain mass media campaign (Don't Take it Lying Down) was implemented in Alberta, Canada. A variety of media formats were used with radio ads predominating because of budget constraints. METHODS: Changes in back pain beliefs were studied using telephone surveys of random samples from intervention and control provinces before campaign onset and afterward. The Back Beliefs Questionnaire (BBQ) was used along with specific questions about the importance of staying active. For evaluating behaviors, we extracted data from governmental and workers' compensation databases between January 1999 and July 2008. Outcomes included indicators of number of visits to health care providers, use of diagnostic imaging, and compensation claim incidence and duration. Analysis included time series analysis and ANOVA testing of the interaction between province and time. RESULTS: Belief surveys were conducted with a total of 8566 subjects over the 4 year period. Changes on BBQ scores were not statistically significant, however, the proportion of subjects agreeing with the statement, "If you have back pain you should try to stay active" increased in Alberta from 56% to 63% (P = 0.008) with no change in the control group (consistently approximately 60%). No meaningful or statistically significant effects were seen on the behavioral outcomes. CONCLUSION: A Canadian media campaign appears to have had a small impact on public beliefs specifically related to campaign messaging to stay active, but no impact was observed on health utilization or work disability outcomes. Results are likely because of the modest level of awareness achieved by the campaign and future campaigns will likely require more extensive media coverage. PMID- 20308944 TI - Giant anterior arachnoid cyst associated with syringomyelia: implications for treatment and follow-up. AB - STUDY DESIGN: A case report of a unique anterior intradural spinal arachnoid cyst (ISAC) associated with syringomyelia. OBJECTIVE: To discuss the surgical treatment and follow-up of anterior ISACs associated with syringomyelia. SUMMARY OF BACKGROUND DATA: Fenestration is commonly performed in arachnoid cysts with a large craniocaudal extension and in arachnoid cysts associated with syringomyelia. Particularly, excision of dorsal arachnoid cysts, without a shunting operation for the syrinx, achieves excellent results. However, anterior arachnoid cysts are different from dorsal cysts in having a greater craniocaudal extension and showing intracystic fibrous septae. METHODS: A 55-year-old man presented a small syringomyelic cavity at C1/C2 level and a giant anterior extramedullary intradural cystic cavity spreading from C1 to T11. A posterior laminectomy at C3 level was performed, and generous fenestration of the cyst was followed by the positioning of a cyst-subarachnoid shunt. RESULTS: After surgery, transitory relief was soon followed by a progressive worsening of symptoms. A specific kinematic-magnetic resonance imaging (K-MRI) was then carried out, showing a regular sisto-diastolic modulation of flow and normal shunt function. To define the real fluid dynamics within the cyst, the patient underwent a computed tomography-myelography (CT-M). Only a small quantity of contrast was found inside the pouch, confirming the clinical diagnosis of a poor communication within the shunt and the failure of previous surgery. CONCLUSION: This is the most extensive anterior ISAC associated with syringomyelia reported in literature until now. The treatment of extensive intradural extramedullary arachnoid cysts, especially for those located ventral to the spine and associated with syringomyelia, is still a matter of debate. In our case, fenestration and insertion of a cyst-subarachnoid shunt alone were not sufficient to restore normal CSF dynamics. In addition, we show that K-MRI may not be a proper method for postoperative follow-up of these lesions. PMID- 20308945 TI - Nerve root sedimentation sign: evaluation of a new radiological sign in lumbar spinal stenosis. AB - STUDY DESIGN: Retrospective case-referent study. OBJECTIVE: To assess whether the new sedimentation sign discriminates between nonspecific low back pain (LBP) and symptomatic lumbar spinal stenosis (LSS). SUMMARY OF BACKGROUND DATA: In the diagnosis of LSS, radiologic findings do not always correlate with clinical symptoms, and additional diagnostic signs are needed. In patients without LSS, we observe the sedimentation of lumbar nerve roots to the dorsal part of the dural sac on supine magnetic resonance image scans. In patients with symptomatic and morphologic central LSS, this sedimentation is rarely seen. We named this phenomenon "sedimentation sign" and defined the absence of sedimenting nerve roots as positive sedimentation sign for the diagnosis of LSS. METHODS: This study included 200 patients. Patients in the LSS group (n = 100) showed claudication with or without LBP and leg pain, a cross-sectional area <80 mm, and a walking distance <200 m; patients in the LBP group (n = 100) had LBP, no leg pain, no claudication, a cross-sectional area of the dural sac >120 mm, and a walking distance >1000 m. The frequency of a positive sedimentation sign was compared between the 2 groups, and intraobserver and interobserver reliability were assessed in a random subsample (n = 20). RESULTS: A positive sedimentation sign was identified in 94 patients in the LSS group (94%; 95% confidence interval, 90%-99%) but none in the LBP group (0%; 95% confidence interval, 0% 4%). Reliability was kappa = 1.0 (intraobserver) and kappa = 0.93 (interobserver), respectively. There was no difference in the detection of the sign between segmental levels L1-L5 in the LSS group. CONCLUSION: A positive sedimentation sign exclusively and reliably occurs in patients with LSS, suggesting its usefulness in clinical practice. Future accuracy studies will address its sensitivity and specificity. If they confirm the sign's high specificity, a positive sedimentation sign can rule in LSS, and, with a high sensitivity, a negative sedimentation sign can rule out LSS. PMID- 20308946 TI - Combined occipital-cervical and atlantoaxial disassociation without neurologic injury: case report and review of the literature. AB - STUDY DESIGN: Case report and literature review. OBJECTIVE: To discuss the diagnosis, limitations, and treatment of combined occipital-cervical and atlantoaxial disassociation with normal neurologic function. SUMMARY OF BACKGROUND DATA: Injuries to the craniocervical junction can lead to devastating neurologic deficits. Occipital-cervical disassociation is a well-documented injury pattern that can lead to pain, spinal cord injury, and death. Early diagnosis and treatment can preserve neurologic function. Combined injuries to both the occipital-cervical and atlantoaxial segments are less common and, to date, have only been described with severe neurologic injury. METHODS: Retrospective review of a case. Literature review was performed through Medline and Pubmed searches. RESULTS: This is the first case to present a combined occipital-cervical and atlantoaxial disassociation with a neurologically intact patient. Initial physical examination was limited, but early imaging revealed evidence of instability. Early diagnosis and early (< 24) surgical stabilization was performed with no complications and neurologic preservation. One-year follow up visit revealed normal neurologic examination with neck pain VAS = 2/10 and neck disability index = 6. CONCLUSION: Combined injuries to the occipital cervical and atlantoaxial can result in upper cervical instability. Despite previous reports, neurologic preservation remains a possibility in this injury pattern. Limitations in physical examination and radiographic imaging persist, but early diagnosis and surgical stabilization may improve neurologic outcomes. PMID- 20308947 TI - Multiple lumbar pedicle fractures in osteopetrosis: a case report. AB - STUDY DESIGN: Single case report. OBJECTIVE: To report the observation of multiple lumbar pedicle fractures in a patient with osteopetrosis. SUMMARY OF BACKGROUND DATA: Osteopetrosis is characterized by osteoclast dysfunction, impaired bone resorption, and poor bone remodeling. As a result, the bone is brittle but hard and is referred to as "marble bone disease." Although long bone fractures are relatively common, fractures of the spine are rare. Spondylolysis has been reported in the cervical and lumbar spine, and pedicle fractures have been reported in the cervical spine. We report the case of a patient with autosomal dominant osteopetrosis with multiple lumbar pedicle fractures. To the best of our knowledge, there have been no previous reports of multiple lumbar pedicle fractures in osteopetrosis. METHODS: A 73-year-old woman, with a known history of osteopetrosis, presented with acute nonradiating low back pain following a bout of coughing. The lower limb neurology and bladder and bowel function were normal. The imaging findings, clinical course, and treatment are discussed. RESULTS: Initial computed tomography scans of the patient revealed the presence of multiple pedicle fractures with spondylolysis. The patient was advised bed rest for the first 3 days, and when the acute pain subsided, she was permitted to ambulate with a lumbosacral corset. The patient was asymptomatic for 8 months, when she was readmitted with another episode of acute low back pain. The CT scan revealed fresh fracture of the L4 pedicle, which was not seen on the previous scan. The pain settled down again with conservative measures. CONCLUSION: This case report discusses the rare occurrence of multiple lumbar pedicle fractures and pars interarticularis (spondylolysis) fractures in a patient with osteopetrosis. PMID- 20308956 TI - Heart failure in search of a cure. PMID- 20308957 TI - Abnormal mitochondrial function during ischemia reperfusion provides targets for pharmacological therapy. AB - The concept of reperfusion injury has been a subject of intense debate. Some researchers believe that the entire injury develops during the ischemic period, whereas others argue that blood reflow extends tissue injury due to the release of oxygen-derived free radicals, an inflammatory reaction involving influx of various populations of immune cell, and dysregulation of intracellular and particularly mitochondrial calcium concentration. Mitochondrial calcium overload in the presence of oxygen-derived free radicals can result in the opening of the mitochondrial permeability transition pore (mPTP), which further compromises cellular energetics. The resultant low ATP and altered ion homeostasis lead to a rupture of the plasma membrane and cell death. Mitochondria have long been proposed as one of the main players in cell death, since the mitochondria are central to synthesis of both ATP and the formation of oxygen-derived free radicals. These mechanisms are centered on mitochondrial calcium overload as a key component of cell death. Pharmacological strategies that are cardioprotective attempt to reduce mitochondrial calcium overload to decrease the likelihood of arrhythmias and cardiac dysfunction elicited by reperfusion. PMID- 20308958 TI - Inflammation a potential target for therapeutic intervention in heart failure. PMID- 20308959 TI - Glucose management, heart failure and transplantation. PMID- 20308960 TI - Percutaneous device therapy to prevent and treat acute decompensated heart failure. PMID- 20308961 TI - Computational fluid dynamics as a tool for visualizing hemodynamic flow patterns. AB - Computational fluid dynamics (CFD) techniques have progressed to a point where they can be routinely applied towards the simulation of blood flow dynamics in the human vasculature. Patient-specific geometries and physiologically accurate flow rates can be obtained from clinical images to provide accurate boundary conditions for these simulations. Advances in computer hardware and CFD software in recent years have reduced the simulation computing time from days to hours. Such a time frame permits incorporation of the information obtained with CFD into the clinical workflow for the surgical repair vascular pathologies. In this article, the concepts of CFD are introduced via a patient-specific simulation of the hemodynamics in a type III B aortic dissection. Emphasis is placed on the practical aspects of how to optimize CFD simulations so that their results may be of clinical value to the treating surgeon. Limitations as they exist today are discussed. PMID- 20308962 TI - Heart failure research: translating basic science into therapies. AB - Congestive heart failure is a syndrome characterized by decreased cardiac output with consequent neurohormonal activation leading to water and salt retention. This ultimately results in pulmonary and vascular congestion with eventual organ hypoperfusion and death. Often described as a "vicious cycle", congestive heart failure is responsible for more than 40,000 deaths per year in the United States and plays a substantial role in another 250,000 deaths; it takes a financial toll as well, with approximately $34 billion spent each year on the medical care of patients. The key to ending this vicious cycle is applied research. The Department of Cardiology within The Methodist Hospital is conducting research aimed at understanding heart failure and working towards therapies to improve patient care. PMID- 20308963 TI - The evolution of nuclear cardiology takes us back to the beginning to develop today's "new standard of care" for cardiac imaging: how quantifying regional radioactive counts at five and 60 minutes post-stress unmasks hidden ischemia. PMID- 20308964 TI - Michael E. DeBakey, M.D.: beloved brother, master mentor, compatible colleague, professional paragon. PMID- 20308966 TI - Does physical activity affect quality of life, disease symptoms and immune measures in patients with inflammatory bowel disease? A systematic review. AB - Inflammatory bowel diseases (IBD) are a group of chronic, episodic inflammatory conditions of the large and small intestines. Individuals with IBD have been reported to use physical activity (PA) as a complementary therapy although the effectiveness of PA for reducing disease burden in patients with IBD is not known. The review objective is to evaluate published studies on physical activity and IBD focusing on quality of life, disease burden markers and immunological outcomes. A literature search was carried out using MEDLINE, WEB OF SCIENCE, CINHAL, and SCOPUS (to December 2008). Studies were included if they 1) were provided in English; 2) dealt with IBD in humans; 3) focused on the outcome measures of health related quality of life, clinical disease indicators or immune function; and 4) included PA as a primary intervention for IBD cases. In total, 7 studies were included in this systematic review: 5 were on PA and quality of life measures and inflammatory disease markers, and 2 on PA and immune measures. Four studies showed that PA significantly increased quality of life for IBD patients as assessed by various questionnaires. PA was also associated with decreased disease activity. There was no evidence that PA affected immune outcomes in patients with IBD. The role of PA as an adjunctive therapy for patients with IBD has not been well characterized in the literature. However, there is some evidence that PA may improve quality of life and reduce disease activity in patients with IBD. PMID- 20308967 TI - Physiological profile of water polo players in different competitive levels. AB - AIM: The purpose of this study was to determine if there are different physiological characteristics in water polo players of three different competitive levels (national team, NT, junior national team, NJ, and amateur club, AC). METHODS: To better define the training levels of water polo players competing at different levels, we administered a shuttle swim test (SST, a specific test used by Italian coaches) and a classic speed-lactate test. The shuttle swim test is based on actions at maximum intensity followed by incomplete recoveries. To compare the athletes, we used their morphological characteristics, the speed during an incremental test associated with fixed blood lactate concentrations of 2 mmol*1-1 (Aerobic Threshold, AT) and 4 mmol*1-1 (Anaerobic Threshold, AnT), and the SST data (speed, heart rate and lactate concentration). RESULTS: The heart rate at the end of the SST was 164+/-12 beats*min-1 for NT, 166+/-10 beats*min-1 for NJ (no significant difference, P>0.05) and 179+/-9 beats*min-1 for AC (significantly different from NT and NJ, P<0.05). The AT and AnT speeds were significantly higher in NT than in AC and NJ (P<0.05). No significant differences were found in AT and AnT speeds between AC and NJ (P>0.05). The mean speed during the shuttle swim test was significantly higher in NT and NJ than in AC (P<0.05). Lactate values were similar in the NT, AC and NJ groups (P>0.05). The SST mean speed was significantly correlated with the AT (P<0.01) and AnT speeds (P<0.05) in three groups . In all groups no significant correlation was found between SST blood lactate and AT or AnT speeds (P>0.05). CONCLUSION: Some differences were found among the senior and junior professional and amateur water polo players in both SST performance and Aerobic and Anaerobic Thre-shold speeds. The shuttle swim test for water polo provides conditioning coaches and sport scientists with data on the sport-specific movement speed and the competition-specific fatigue resistance in each athlete. PMID- 20308968 TI - Oxygen cost of sprint training. AB - AIM: The purpose of the study was to profile the oxygen uptake of sprinters during various portions of a typical sprint training workout. METHODS: This was a descriptive study of 11 female sprinters and jumpers on an NCAA Division II university track team. Subjects were assessed for VO(2max), and VO(2) and HR kinetics during a 65 min typical sprint training session on a treadmill. The sprint session included a warm-up, static stretching, acceleration runs, 8x20 s sprints at 150% of velocity VO(2max) (vVO(2max)) with a 3-min walk recovery, and a cool-down. RESULTS: Mean VO(2) and HR (M+/-SD) for the entire 65 min sprint training session were 19.1+/-7.6 mL/kg/min and 138.7+/-24.0 b/min, respectively. VO(2) rose to 33 mL/kg/min during and immediately following each 20 s sprint which represented 73% of VO(2max). VO(2) during and after each sprint remained nearly constant (P>0.05) rather than rising as hypothesized. CONCLUSION: VO(2) during a 65 min sprint training workout in female college athletes varies greatly but was elevated to 33 mL/kg/min following each 20 s sprint. VO(2) did not rise across the series of eight sprints. These results suggest that chronic sprint training may elicit a moderate aerobic training effect. Implications for training are discussed. PMID- 20308969 TI - Aerobic power assessment by using a 10 min heart rate control running on treadmill. AB - AIM: This study evaluated the reliability and validity of a proposed 10 min running speed variance test (RSVHRC) in assessing aerobic power at which the intensity was controlled at 80% of age-predicted maximal heart rate (HR). METHODS: Forty-four college students (21 men and 23 women, age: 21+/-3 years, height: 166.6+/-7.9 cm, weight: 61.7+/-9.3 kg) were recruited to undergo 2 RSVHRC test trials, and a maximal exercise test at least 24 hours apart. The test consisted of a 3-min warm-up at 1.67 km/h, followed by adjusting speed up to either at 2.5 m/s or 2.78 m/s immediately depending upon onset HR after the warm up. HR was monitored every 30 seconds and running speed was adjusted accordingly to maintain HR (+/-5bpm) for 10 minutes. RSVHRC was determined by the slope of distance/time relationship from 3rd to 10th min. RESULTS: Pair t-test showed that there was no significant difference between 1st (2.38+/-0.58 m/s) and 2nd trial (2.40+/-0.63 m/s). Intraclass correlation coefficient (ICC) score showed that RSVHRC was highly reliable (ICC=0.98, 95% CI=0.97-0.99). Coefficient of variation, standard error of measurement (SEM), and %SEM were 4.8%, 0.12 m/s, 5.02% respectively. Additionally, a Pearson product-moment correlation coefficient demonstrated 2 trials were correlated with maximal oxygen uptake (46.6+/-8.1 mL/kg/min) at r=0.74, 0.71 (P<0.05). CONCLUSION: In conclusion, 80%HRmax RSVHRC is an easy and highly reliable submaximal exercise test that provides good validity to assess aerobic power in young and healthy population, which can be applied on treadmill setting. PMID- 20308970 TI - Inter-relationships between machine squat-jump strength, force, power and 10 m sprint times in trained sportsmen. AB - AIM: Strength and conditioning practitioners appear focussed on developing maximal strength based on the premise that it underpins explosive muscular performance. Investigation into the relationship between strength and a multitude of explosive power measures is limited though. Furthermore, the relationship of explosive force and power with functional performance is unclear. METHODS: We examined the inter-relationships between maximal strength and explosive measures of force and power at different loads. Also investigated were the relationships between explosive measures and 10-m sprinting ability. Forty elite-level well trained rugby union and league athletes performed 10-m sprints followed by bilateral concentric-only machine squat-jumps at 20 and 80%1RM. The magnitudes of the inter-relationships between groups of force measures, power measures and sprint times were interpreted using Pearson correlation coefficients, which had uncertainty (90% confidence limits) of approximately +/-0.25. Measures investigated included peak force, peak power, rate of force development, and some of Zatsiorsky's explosive measures, all expressed relative to body mass. RESULTS: The relationship between maximal strength and peak power was moderate at 20 %1RM (r=0.32) but trivial at 80 %1RM (r=-0.03). Practically no relationship between any of the explosive measures and 10-m sprint ability was observed (r=-0.01 to 0.06). CONCLUSION: Although correlations do not imply cause and effect, we speculate that the common practice of focussing on high levels of maximal strength in a machine squat to improve power output may be misguided. Our results also cast doubt on the efficacy of increasing explosive force and power in a machine squat-jump with the intention of improving sprint ability in well-trained athletes. PMID- 20308971 TI - Effects of three distinct protocols of fitness training on body composition, strength and blood lactate. AB - AIM: Circuit training is a very popular methodology in fitness program because it allows to join together cardiovascular and strength training. The purpose of this study was to determine the physiological effects of circuit training performed at different intensities on body composition, strength and blood lactate in middle aged subjects who had recently undergone only minimum physical training. METHODS: Forty participants (aged 50-65) were assigned to a control group (CG) or to one of the three exercise treatment groups: Endurance Group (EG), Circuit-Low Intensity Group (CLG), Circuit-High Intensity Group (CHG). The three groups exercised three times per week, 50 min per session for 12 wk using EG (N.=10), CLG (N.=10) or CHG (N.=10). Pre- and post-training, participants RESULTS: Among the three groups, CHG showed the greatest reductions in body weight (BW), percentage of fat mass (FM), waistline, blood lactate (produced at 100 Watt during submaximal test) and greater improvement in 6RM in horizontal leg press and underhand cable pulldowns. CONCLUSION: The results obtained favored the conclusion that high-intensity exercise combined with endurance training in the circuit training technique is more effective than endurance training alone or low intensity circuit training in improving body composition, blood lactate, moreover CHG results in significantly greater strength increase compared to traditional circuit training. PMID- 20308972 TI - A single oral intake of arginine does not affect performance during repeated Wingate anaerobic test. AB - AIM: The ergogenic effect of arginine has been demonstrated in research focusing on its intake before exercise. However, in these studies, the effect of arginine in combination with other various metabolites were assessed. The aim of this study was to determine whether a single oral intake of arginine, without any other compounds, 60 minutes prior to exercise, modifies performance and exercise metabolism during a repeated Wingate anaerobic test. METHODS: Six healthy, active, but not highly trained volunteers participated in the study. Subjects performed three 30s all-out supramaximal Wingate Anaerobic Tests (WAnTs) with 4 minute-interval rest periods between WAnTs. RESULTS: Arginine ingestion before exercise did not influence physical performance. Triple WAnTs resulted in a marked increase in white blood cell (WBC) count, lactate and ammonia concentrations, however there were no differences between arginine and the placebo trials. CONCLUSION: Our data indicated that 2 g of arginine ingested in a single dose, neither induced nitrite/nitrate (NOx) concentrations changes, nor improved physical performance. PMID- 20308973 TI - Effects of chronic Rhodiola Rosea supplementation on sport performance and antioxidant capacity in trained male: preliminary results. AB - AIM: Rhodiola Rosea, is an adaptogen plant which has been reported to promote fatty acids utilisation, to ameliorate antioxidant function, and to improve body resistance to physical strenuous efforts. The purpose of the present study was to investigate the effects on physical performance as well as on the redox status of a chronic Rhodiola Rosea supplementation in a group of competitive athletes during endurance exercise. METHODS: Following a chronic supplementation with Rhodiola Rosea for 4 weeks, 14 trained male athletes underwent a cardio-pulmonary exhaustion test and blood samples to evaluate their antioxidant status and other biochemical parameters. These data were compared with those coming from the same athletes after an intake of placebo. RESULTS: The evaluation of physical performance parameters showed that HR Max, Borg Scale level, VO(2) max and duration of the test were essentially unaffected by Rhodiola Rosea assumption. On the contrary, Rhodiola Rosea intake reduced, in a statistically significative manner, plasma free fatty acids levels. No effect on blood glucose was found. Blood antioxidant status and inflammatory parameters resulted unaffected by Rhodiola Rosea supplementation. Blood lactate and plasma creatine kinase levels were found significantly lower (P<0.05) in Rhodiola Rosea treated subjects when compared to the placebo treated group. CONCLUSION: Chronic Rhodiola Rosea supplementation is able to reduce both lactate levels and parameters of skeletal muscle damage after an exhaustive exercise session. Moreover this supplementation seems to ameliorate fatty acid consumption. Taken together those observation confirm that Rhodiola Rosea may increase the adaptogen ability to physical exercise. PMID- 20308974 TI - Bilateral suprascapular nerve entrapment by glenoid labral cysts associated with rotator cuff damage and posterior instability in an amateur weightlifter. AB - Suprascapular nerve entrapment is a common condition in athletes. The entrapment is most frequently due to a "glenoid labral cyst" produced by joint fluid extrusion in consequence of labral degenerative changes. The bilaterality of the entrapment and the association with rotator cuff pathology are a rare evidence. We present the case of a 38-year-old amateur weightlifter with an history of left shoulder chronic posterior pain and progressive external rotation weakness, and with an acute right shoulder pain and weakness. Magnetic resonance imaging showed a bilateral glenoid labral cyst in association with partial tear of the supraspinatus tendon, atrophy of the infraspinatus muscle and type 2 SLAP lesion at the left shoulder and subacromial impingement syndrome (due to acromio clavicular osteophyte), mild atrophy of the infraspinatus muscle and type 1-2 SLAP lesion at the right side. PMID- 20308975 TI - High grade splenic rupture in an elite Rugby Union player. AB - The authors present the case of an amateur under-18 international squad Rugby Union player who sustained a Grade III splenic rupture while scoring a try. He was admitted to hospital and treated with strict bedrest following initial computed tomography (CT) evaluation. He maintained hemodynamic stability throughout and registered no drop in hemoglobin. A repeat CT scan five days later showed no radiological progression and he was discharged with instructions to avoid exercise for three months. A follow-up CT scan performed at 10 weeks after the injury showed radiological resolution but the decision was made to avoid physical contact for a further three months. The player made a full recovery and is now back playing representative rugby. This report reviews the management and raises the question as to when players should be allowed back to play contact sports following a splenic rupture. PMID- 20308976 TI - Gender comparison of C-reactive protein and cardiovascular disease risk in college students and intercollegiate athletes. AB - AIM: Research involving coronary artery disease (CAD) risk in young adults is limited; therefore we compared cardiovascular risk between college-aged men and women. METHODS: Thirty college men and women volunteered as study subjects. CAD risk assessment included systolic blood pressure (SBP), diastolic blood pressure (DBP), waist circumference, percent body fat (%BF), maximum oxygen consumption, fasting plasma C-reactive protein (CRP), total cholesterol (TC), high-density lipoprotein-cholesterol (HDL-C), Body Mass Index (BMI) and fasting glucose. Risk factors were compared between groups using a t-test and Pearson product moment correlations were used to determine the relationships between CRP and CAD risk factors. RESULTS: Statistically significant differences were observed for HDL, TC/HDL ratio, SBP, and %BF, between men and women. Total cholesterol and CRP concentration were not different between men and women. Log CRP was positively correlated with %BF and BMI. Further, 47% of the subjects met the criteria for one or more risk factors for CAD, as specified by the American College of Sports Medicine. CONCLUSION: Our data indicate a gender difference in CAD risk in college students with similar reported activity. Waist circumference, fasting glucose, % body fat, and BMI are associated with CRP in college age men and women. PMID- 20308977 TI - Eating attitudes, self-esteem and social physique anxiety among Iranian females who participate in fitness programs. AB - AIM: Today, women's participation in sports has substantially increased. This growth has been accompanied by concerns about health risks, as eating disorders, and psychological features, as self-esteem (SE) and social physique anxiety (SPA). The purpose of this study was to determine disordered eating attitudes and their relation to SE, SPA, as well as body weight, and body mass index (BMI), in Iranian females who participate in fitness programs. METHODS: Subjects were 250 females, aged 14-51 years, who participated in fitness programs. Eating attitude test-26 (EAT-26), Rosenberg's self esteem scale (RSES), and social physique anxiety scale (SPAS), were used. Body weight and height were measured, and then Body Mass Index (BMI) was calculated. RESULTS: According to BMI cut-offs, 36% of subjects were overweight or obese. 28.4% and 19.6% of subjects were disordered eating attitudes (EAT-26>or=20) and low self-esteem (RSES<15), respectively. Disordered eating attitude subjects had lower SE and higher SPA, body weight and BMI than normal subjects (P<0.05). The low SE group had higher SPAS than normal one (P<0.02). In bivariate analysis, EAT-26 score was correlated negatively with RSES (r=-0.13, P<0.04) and positively with body weight, BMI, and SPAS (r=0.40, 0.42, and 0.47, respectively, P<0.001). SPAS had positive correlation with body weight and BMI (r=0.22, 0.19, CONCLUSION: It can be concluded that disordered eating attitudes are prevalent among Iranian females who participate in fitness programs. In this group, high SPA, body weight and BMI, and low SE accompany disordered eating attitudes. PMID- 20308978 TI - Validating the salivary testosterone and cortisol concentration measures in response to short high-intensity exercise. AB - AIM: To validate the testosterone (T) and cortisol (C) concentration measures in saliva in response to short high-intensity exercise. METHODS: Nine healthy males provided matching saliva and plasma samples before and after a 30-second Wingate cycle test. Saliva was assayed for T (Sal-T) and C (Sal-C) concentrations, and plasma for total T and total C, sex hormone-binding globulin, corticosteroid binding globulin (CBG) and albumin concentrations. The plasma free and bioavailable hormones were calculated. RESULTS: The Sal-T and plasma T correlations were weak to moderate (r=0.57-0.61) when examined between individuals (pooled data for all participants), but these relationships improved (r = 0.71-0.73) within individuals (data for each participant on average). The Sal-C and plasma C correlations were strong both between individuals (r=0.81 0.84) and within individuals (r=0.83-0.84). The peak relative increases in Sal-T (35+/-9%) and Sal-C (63+/-29%) concentrations exceeded the plasma total and/or free hormones, but not the bioavailable hormones. Albumin (10+/-3%) and CBG (16+/ 4%) also increased with exercise, along with blood lactate (943+/-119%). CONCLUSION: The Sal-T and Sal-C concentration measures were validated in response to short high-intensity exercise, especially for individuals. The hormonal changes in saliva were also more sensitive to exercise (i.e. greater relative responses) than the plasma total and/or free hormones, potentially arising from changes in the binding proteins and blood lactate. These findings support the use of saliva as a medium for steroid determination in sport. PMID- 20308979 TI - Effect of different exercise intensities on oxidative stress markers and antioxidant response in trained cyclists. AB - Traditionally, physical activity has been associated with beneficial effects on the organism. However, exercise has been shown to increase the production of reactive oxygen species (ROS) to a point that can exceed antioxidant defences, causing oxidative stress. Characteristics of exercise such as the intensity or duration seem to be associated with oxidative damage. The aim of this study was to evaluate the effect of exercise of two different cycling intensities on oxidative stress and antioxidant response in trained males. Twenty male trained cyclists participated in this study. The maximal exercise test consisted of an incremental cycling test until voluntary exhaustion, and the submaximal test was a steady state at 75% VO(2max) for 30 min on a cycloergometer. In maximal exercise test (16+/-4 min of cycling), the results showed an increase in malondialdehyde (MDA) from 40.6+/-2.0 to 45.4+/- 18.4 microM (p<0.05) in plasma and from 0.21+/-0.10 to 0.23+/-0.12 micromol/g Hb (P<0.05) in erythrocytes, also vitamin C increased in plasma from 3.80+/-1.60 to 5.20+/-2.16 mg/mL (P<0.05) and it decreased from 130.5+/-34.7 to 83.4+/-30.0 mg/g hemoglobin (P<0.05) in erythrocytes, whereas there were no changes in vitamin E concentrations. In submaximal exercise, no significant differences were obtained in MDA, vitamin C or vitamin E. In conclusion, short time of high intensity cycling leads to oxidative stress increasing plasma and decreasing erythrocyte vitamin C levels. PMID- 20308980 TI - A study of saccadic eye movement dynamics in volleyball: comparison between athletes and non-athletes. AB - AIM: Visual search strategy in sports may influence performance. Thus it is interesting to investigate oculo-motor behavior of athletes and its possible impingement upon sport training and coaching. The differences in fixations and saccadic eye movements between expert volleyball players and novice subjects was studied, by carrying out a precise analysis of gaze shifts during the observation of a standard game situation. METHODS: Fifteen professional athletes and fifteen non athletes watched at a volleyball filmed sequence in which a setter receives a pass tossed from the coach and sets it forward or backward. Then, the number and duration of fixations to specific interest areas (IAs) were counted. In addition, the sequences of saccades from each IA to the others were analyzed. RESULTS: The results showed that expert players performed fewer fixations of longer duration and spent more time looking first at the initial pass trajectory and then at the setter's hands, disregarding the ball trajectory. The non athletes, instead, followed the whole course of the ball, before and after the hands touch. CONCLUSION: These findings support the interpretation that experts volleyball players extract more task-relevant information from each fixation than do less skilled athletes, and that player's proficiency influences the strategy used in the treatment of visual information. PMID- 20308981 TI - Real time VO2 measurements during soccer match-play. PMID- 20308982 TI - Isolation and enrichment of rat mesenchymal stem cells (MSCs) and separation of single-colony derived MSCs. AB - MSCs are a population of adult stem cells that is a promising source for therapeutic applications. These cells can be isolated from the bone marrow and can be easily separated from the hematopoietic stem cells (HSCs) due to their plastic adherence. This protocol describes how to isolate MSCs from rat femurs and tibias. The isolated cells were further enriched against two MSCs surface markers CD54 and CD90 by magnetic cell sorting. Expression of surface markers CD54 and CD90 were then confirmed by flow cytometry analysis. HSC marker CD45 was also included to check if the sorted MSCs were depleted of HSCs. MSCs are naturally quite heterogeneous. There are subpopulations of cells that have different shapes, proliferation and differentiation abilities. These subpopulations all express the known MSCs markers and no unique marker has yet been identified for the different subpopulations. Therefore, an alternative approach to separate out the different subpopulations is using cloning cylinders to separate out single-colony derived cells. The cells derived from the single colonies can then be cultured and evaluated separately. PMID- 20308983 TI - Blockade of interaction of alpha9 integrin with its ligands hinders the formation of granulation in cutaneous wound healing. AB - The wound healing is a complex process consisting of inflammatory reaction, proliferation of mesenchymal cells, and formation and contraction of granulation tissue. The integrin receptors have crucial roles in this process. Recently, alpha9 integrin has also been detected on keratinocytes within wound sites. However, its functional significance at various wound healing processes was not fully elucidated. To address the role of alpha9 integrin in wound healing process, we made a full-thickness skin excisional wound and treated mice with anti-alpha9 integrin antibody. It has been shown that wound healing process was divided into three distinct phases: first, the re-epithelialization phase, second, the phase of granulation tissue formation, and finally the phase of contraction of granulation tissue. We found that contraction of granulation tissue was not impaired by blocking the interaction of alpha9 integrin with its ligands, indicating that alpha9 integrin is not involved in myofibroblast differentiation. It is noteworthy that the formation of granulation tissue, as characterized by dense vimentin and CD31-positive area, was impaired. The hindrance of granulation tissue formation is because of the inhibition of adhesion and migration of alpha9 integrin-positive dermal fibroblasts. In conclusion, alpha9 integrin is involved in the formation of granulation tissue through regulating migration and adhesion of dermal fibroblasts in the full thickness skin excisional wound model. PMID- 20308984 TI - Bone marrow mononuclear cells attenuate fibrosis development after severe acute kidney injury. AB - One of the early phases that lead to fibrosis progression is inflammation. Once this stage is resolved, fibrosis might be prevented. Bone marrow mononuclear cells (BMMCs) are emerging as a new therapy for several pathologies, including autoimmune diseases, because they enact immunosuppression. In this study we aimed to evaluate the role of BMMC administration in a model of kidney fibrosis induced by an acute injury. C57Bl6 mice were subjected to unilateral severe ischemia by clamping the left renal pedicle for 1h. BMMCs were isolated from femurs and tibia, and after 6h of reperfusion, 1 x 10(6) cells were administrated intraperitoneally. At 24h after surgery, treated animals showed a significant decrease in creatinine and urea levels when compared with untreated animals. Different administration routes were tested. Moreover, interferon (IFN) receptor knockout BMMCs were used, as this receptor is necessary for BMMC activation. Labeled BMMCs were found in ischemic kidney on FACS analysis. This improved outcome was associated with modulation of inflammation in the kidney and systemic modulation, as determined by cytokine expression profiling. Despite non amelioration of functional parameters, kidney mRNA expression of interleukin (IL) 6 at 6 weeks was lower in BMMC-treated animals, as were levels of collagen 1, connective tissue growth factor (CTGF), transforming growth factor-beta (TGF beta) and vimentin. Protective molecules, such as IL-10, heme oxygenase 1 (HO-1) and bone morphogenetic 7 (BMP-7), were increased in treated animals after 6 weeks. Moreover, Masson and Picrosirius red staining analyses showed less fibrotic areas in the kidneys of treated animals. Thus, early modulation of inflammation by BMMCs after an ischemic injury leads to reduced fibrosis through modulation of early inflammation. PMID- 20308985 TI - Organizing the cell cortex: the role of ERM proteins. AB - Specialized membrane domains are an important feature of almost all cells. In particular, they are essential to tissues that have a highly organized cell cortex, such as the intestinal brush border epithelium. The ERM proteins (ezrin, radixin and moesin) have a crucial role in organizing membrane domains through their ability to interact with transmembrane proteins and the cytoskeleton. In doing so, they can provide structural links to strengthen the cell cortex and regulate the activities of signal transduction pathways. Recent studies examining the structure and in vivo functions of ERMs have greatly advanced our understanding of the importance of membrane-cytoskeleton interactions. PMID- 20308987 TI - Prion-like transmission of protein aggregates in neurodegenerative diseases. AB - Neurodegenerative diseases are commonly associated with the accumulation of intracellular or extracellular protein aggregates. Recent studies suggest that these aggregates are capable of crossing cellular membranes and can directly contribute to the propagation of neurodegenerative disease pathogenesis. We propose that, once initiated, neuropathological changes might spread in a 'prion like' manner and that disease progression is associated with the intercellular transfer of pathogenic proteins. The transfer of naked infectious particles between cells could therefore be a target for new disease-modifying therapies. PMID- 20308986 TI - The final steps of integrin activation: the end game. AB - Cell-directed changes in the ligand-binding affinity ('activation') of integrins regulate cell adhesion and migration, extracellular matrix assembly and mechanotransduction, thereby contributing to embryonic development and diseases such as atherothrombosis and cancer. Integrin activation comprises triggering events, intermediate signalling events and, finally, the interaction of integrins with cytoplasmic regulators, which changes an integrin's affinity for its ligands. The first two events involve diverse interacting signalling pathways, whereas the final steps are immediately proximal to integrins, thus enabling integrin-focused therapeutic strategies. Recent progress provides insight into the structure of integrin transmembrane domains, and reveals how the final steps of integrin activation are mediated by integrin-binding proteins such as talins and kindlins. PMID- 20308988 TI - Environmental enrichment requires adult neurogenesis to facilitate the recovery from psychosocial stress. AB - The subgranular zone of the adult hippocampal dentate gyrus contains a pool of neural stem cells that continuously divide and differentiate into functional granule cells. It has been shown that production of new hippocampal neurons is necessary for amelioration of stress-induced behavioral changes by antidepressants in animal models of depression. The survival of newly born hippocampal neurons is decreased by chronic psychosocial stress and increased by exposure to enriched environments. These observations suggest the existence of a link between hippocampal neurogenesis, stress-induced behavioral changes, and the beneficial effects of enriched environment. To show causality, we subjected transgenic mice with conditionally suppressed neurogenesis to psychosocial stress followed by environmental enrichment. First, we showed that repeated social defeat coupled with chronic exposure to an aggressor produces robust and quantifiable indices of submissive and depressive-like behaviors; second, subsequent exposure to an enriched environment led to extinction of the submissive phenotype, while animals exposed to an impoverished environment retained the submissive phenotype; and third, enrichment was not effective in reversing the submissive and depressive-like behaviors in transgenic mice lacking neurogenesis. Our data show two main findings. First, living in an enriched environment is highly effective in extinguishing submissive behavioral traits developed during chronic social stress, and second, these effects are critically dependent on adult neurogenesis, indicating that beneficial behavioral adaptations are dependent on intact adult neurogenesis. PMID- 20308989 TI - Dynamic molecular and anatomical changes in the glucocorticoid receptor in human cortical development. AB - The glucocorticoid receptor (GR) has a critical role in determining the brain's capacity to respond to stress, and has been implicated in the pathogenesis of psychiatric illness. We hypothesized that key changes in cortical GR occur during adolescence and young adulthood, at a time when individuals are at increased risk of developing schizophrenia, bipolar disorder and major depression. We investigated the mRNA and protein expression of GR in the dorsolateral prefrontal cortex across seven developmental time points from infancy to adulthood. GR mRNA expression, determined by microarray and quantitative real-time PCR, was lowest in neonates and peaked around young adulthood. Western blotting revealed two dynamic patterns of GRalpha protein expression across the lifespan, with N terminal variants displaying differing unique patterns of abundance. GRalpha-A and a 67-kDa GRalpha isoform mirrored mRNA trends and peaked in toddlers and late in adolescence, whereas a 40-kDa isoform, very likely a GRalpha-D variant, peaked in neonates and decreased across the lifespan. GRalpha protein was localized to pyramidal neurons throughout life and most strikingly in young adulthood, but to white matter astrocytes only in neonates and infants (<130 days). These results suggest that the neonatal and late adolescent periods represent critical windows of stress pathway development, and highlight the importance of white matter astrocytes and pyramidal neurons, respectively, at these stages of cortical development. Evidence of dynamic patterns of GR isoform expression and cellular localization across development strengthens the hypothesis that windows of vulnerability to stress exist across human cortical development. PMID- 20308990 TI - Genome-wide copy number variation analysis in attention-deficit/hyperactivity disorder: association with neuropeptide Y gene dosage in an extended pedigree. AB - Attention-deficit/hyperactivity disorder (ADHD) is a common, highly heritable neurodevelopmental syndrome characterized by hyperactivity, inattention and increased impulsivity. To detect micro-deletions and micro-duplications that may have a role in the pathogenesis of ADHD, we carried out a genome-wide screen for copy number variations (CNVs) in a cohort of 99 children and adolescents with severe ADHD. Using high-resolution array comparative genomic hybridization (aCGH), a total of 17 potentially syndrome-associated CNVs were identified. The aberrations comprise 4 deletions and 13 duplications with approximate sizes ranging from 110 kb to 3 Mb. Two CNVs occurred de novo and nine were inherited from a parent with ADHD, whereas five are transmitted by an unaffected parent. Candidates include genes expressing acetylcholine-metabolizing butyrylcholinesterase (BCHE), contained in a de novo chromosome 3q26.1 deletion, and a brain-specific pleckstrin homology domain-containing protein (PLEKHB1), with an established function in primary sensory neurons, in two siblings carrying a 11q13.4 duplication inherited from their affected mother. Other genes potentially influencing ADHD-related psychopathology and involved in aberrations inherited from affected parents are the genes for the mitochondrial NADH dehydrogenase 1 alpha subcomplex assembly factor 2 (NDUFAF2), the brain-specific phosphodiesterase 4D isoform 6 (PDE4D6) and the neuronal glucose transporter 3 (SLC2A3). The gene encoding neuropeptide Y (NPY) was included in a ~3 Mb duplication on chromosome 7p15.2-15.3, and investigation of additional family members showed a nominally significant association of this 7p15 duplication with increased NPY plasma concentrations (empirical family-based association test, P=0.023). Lower activation of the left ventral striatum and left posterior insula during anticipation of large rewards or losses elicited by functional magnetic resonance imaging links gene dose-dependent increases in NPY to reward and emotion processing in duplication carriers. These findings implicate CNVs of behaviour-related genes in the pathogenesis of ADHD and are consistent with the notion that both frequent and rare variants influence the development of this common multifactorial syndrome. PMID- 20308991 TI - Integrative genome-wide association analysis of cytoarchitectural abnormalities in the prefrontal cortex of psychiatric disorders. AB - Cytoarchitectural abnormalities have been described in the prefrontal cortex (PFC) of subjects with psychiatric disorders. We explored the possible genetic causalities that may underlie the cytoarchitectural abnormalities of calbindin containing gamma-aminobutyric acid (GABA)ergic neurons and perineuronal oligodendrocytes in the PFC of subjects with psychiatric disorders by converging results from genome-wide single-nucleotide polymorphism (SNP) scans for the traits and expression SNP (eSNP) associations. In the initial genome-wide scans, we identified several development- and apoptosis-related genes associated with the cytoarchitectural traits. Moreover, the susceptibility gene for bipolar disorder, PPP2R2C, was found to be associated with the number of perineuronal oligodendrocytes. Further eSNP analyses indicated that two novel candidate genes, RAB2A and SLC38A1, were associated with the density of calbindin-positive neurons and the number of perineuronal oligodendrocytes, respectively. Our findings may provide novel insights into the genetic causalities associated with cytoarchitectural abnormalities in the PFC of subjects with major psychiatric disorders as well as into the etiology of such disorders. PMID- 20308992 TI - Olanzapine promotes fat accumulation in male rats by decreasing physical activity, repartitioning energy and increasing adipose tissue lipogenesis while impairing lipolysis. AB - Olanzapine and other atypical antipsychotics cause metabolic side effects leading to obesity and diabetes; although these continue to be an important public health concern, their underlying mechanisms remain elusive. Therefore, an animal model of these side effects was developed in male Sprague-Dawley rats. Chronic administration of olanzapine elevated fasting glucose, impaired glucose and insulin tolerance, increased fat mass but, in contrast to female rats, did not increase body weight or food intake. Acute studies were conducted to delineate the mechanisms responsible for these effects. Olanzapine markedly decreased physical activity without a compensatory decline in food intake. It also acutely elevated fasting glucose and worsened oral glucose and insulin tolerance, suggesting that these effects are adiposity independent. Hyperinsulinemic euglycemic clamp studies measuring (14)C-2-deoxyglucose uptake revealed tissue specific insulin resistance. Insulin sensitivity was impaired in skeletal muscle, but either unchanged or increased in adipose tissue depots. Consistent with the olanzapine-induced hyperglycemia, there was a tendency for increased (14)C-2 deoxyglucose uptake into fat depots of fed rats and, surprisingly, free fatty acid (FFA) uptake into fat depots was elevated approximately twofold. The increased glucose and FFA uptake into adipose tissue was coupled with increased adipose tissue lipogenesis. Finally, olanzapine lowered fasting plasma FFA, and as it had no effect on isoproterenol-stimulated rises in plasma glucose, it blunted isoproterenol-stimulated in vivo lipolysis in fed rats. Collectively, these results suggest that olanzapine exerts several metabolic effects that together favor increased accumulation of fuel into adipose tissue, thereby increasing adiposity. PMID- 20308993 TI - A double hit implicates DIAPH3 as an autism risk gene. AB - Recent studies have shown that more than 10% of autism cases are caused by de novo structural genomic rearrangements. Given that some heritable copy number variants (CNVs) have been observed in patients as well as in healthy controls, to date little attention has been paid to the potential function of these non-de novo CNVs in causing autism. A normally intelligent patient with autism, with non affected parents, was identified with a maternally inherited 10 Mb deletion at 13q21.2. Sequencing of the genes within the deletion identified a paternally inherited nonsynonymous amino-acid substitution at position 614 of diaphanous homolog 3 (DIAPH3) (proline to threonine; Pro614Thr). This variant, present in a highly conserved domain, was not found in 328 healthy subjects. Experiments showed a transient expression of Diaph3 in the developing murine cerebral cortex, indicating it has a function in brain development. Transfection of Pro614Thr in murine fibroblasts showed a significant reduction in the number of induced filopodia in comparison to the wild-type gene. DIAPH3 is involved in cell migration, axon guidance and neuritogenesis, and is suggested to function downstream of SHANK3. Our findings strongly suggest DIAPH3 as a novel autism susceptibility gene. Moreover, this report of a 'double-hit' compound heterozygote for a large, maternally inherited, genomic deletion and a paternally inherited rare missense mutation shows that not only de novo genomic variants in patients should be taken seriously in further study but that inherited CNVs may also provide valuable information. PMID- 20308994 TI - Exploring functional polymorphisms in the dopamine receptor D2 gene using prolactin concentration in healthy subjects. PMID- 20308996 TI - The largest Last Supper: depictions of food portions and plate size increased over the millennium. AB - Portion sizes of foods have been noticably increasing in recent years, but when did this trend begin? If art imitates life and if food portions have been generally increasing with time, we might expect this trend to be reflected in paintings that depict food. Perhaps the most commonly painted meal has been that of Jesus Christ's Last Supper, chronicled in the New Testament of the Bible. A CAD-CAM analysis of the relative food-to-head ratio in 52 representative paintings of the Last Supper showed that the relative sizes of the main dish (entree) (r=0.52, P=0.002), bread (r=0.30, P=0.04), and plates (r=0.46, P=0.02) have linearly increased over the past millennium. PMID- 20308995 TI - The pathogenesis of tendinopathy: balancing the response to loading. AB - Tendons are designed to withstand considerable loads. Mechanical loading of tendon tissue results in upregulation of collagen expression and increased synthesis of collagen protein, the extent of which is probably regulated by the strain experienced by the resident fibroblasts (tenocytes). This increase in collagen formation peaks around 24 h after exercise and remains elevated for about 3 days. The degradation of collagen proteins also rises after exercise, but seems to peak earlier than the synthesis. Despite the ability of tendons to adapt to loading, repetitive use often results in injuries, such as tendinopathy, which is characterized by pain during activity, localized tenderness upon palpation, swelling and impaired performance. Tendon histological changes include reduced numbers and rounding of fibroblasts, increased content of proteoglycans, glycosaminoglycans and water, hypervascularization and disorganized collagen fibrils. At the molecular level, the levels of messenger RNA for type I and III collagens, proteoglycans, angiogenic factors, stress and regenerative proteins and proteolytic enzymes are increased. Tendon microrupture and material fatigue have been suggested as possible injury mechanisms, thus implying that one or more 'weak links' are present in the structure. Understanding how tendon tissue adapts to mechanical loading will help to unravel the pathogenesis of tendinopathy. PMID- 20308997 TI - Subacute sensory ataxia and optic neuropathy with thiamine deficiency. AB - BACKGROUND: A 71 year-old man with a history of partial gastrectomy presented to the emergency department with subacute gait instability associated with painful dysesthesias and clumsiness in both hands. 10 years before presentation he had received a diagnosis of megaloblastic anemia, with no neurological involvement, as a result of vitamin B(12) and folate deficiency, for which he was receiving regular supplements. INVESTIGATIONS: Neurological examination; routine laboratory testing; MRI of the spine and brain; lumbar puncture; electromyography; sensory, motor and visual evoked potentials, optic nerve optical coherence tomography; immunoelectrophoresis; cryoglobulins; immunological and infection tests; screening for onconeural antibodies; measurement of serum metabolic values, including vitamins B(12) and E, folates, homocysteine, copper, zinc and pyruvic acid; transketolase activity; gastrointestinal endoscopies; and the glucose breath test. DIAGNOSIS: Subacute sensory ataxia with bilateral optic neuropathy related to thiamine deficiency resulting from remote partial gastrectomy. MANAGEMENT: Parenteral thiamine supplementation followed by chronic oral thiamine and short-term, low-dose multivitamins. PMID- 20308998 TI - HDL metabolism and activity in chronic kidney disease. AB - Chronic kidney disease (CKD) is associated with development of atherosclerosis and premature death from cardiovascular disease. The predisposition of patients with CKD to atherosclerosis is driven by inflammation, oxidative stress and dyslipidemia, all of which are common features of this condition. Markers of dyslipidemia in patients with advanced CKD are impaired clearance and heightened oxidation of apolipoprotein-B-containing lipoproteins and their atherogenic remnants, and a reduction of the plasma concentration, antioxidant, and anti inflammatory properties of high-density lipoprotein (HDL). Studies in animal models of CKD indicate that the disease promotes lipid accumulation in the artery wall and kidney, leading to atherosclerosis, glomerulosclerosis and tubulointerstitial injury. These effects seem to be mediated by an increased cellular influx of lipids, elevated cellular production and reduced cellular catabolism of fatty acids, and impaired antioxidant, anti-inflammatory and reverse lipid transport properties of HDL. Available pharmacological therapies have been largely ineffective in ameliorating oxidative stress, inflammation, HDL deficiency and/or dysfunction, and the associated atherosclerosis and cardiovascular disease in patients with end-stage renal disease. This Review aims to provide an overview of the mechanisms and consequences of CKD-induced HDL deficiency and dysfunction. PMID- 20308999 TI - Metabolic acidosis: pathophysiology, diagnosis and management. AB - Metabolic acidosis is characterized by a primary reduction in serum bicarbonate (HCO(3)(-)) concentration, a secondary decrease in the arterial partial pressure of carbon dioxide (PaCO(2)) of approximately 1 mmHg for every 1 mmol/l fall in serum HCO(3)(-) concentration, and a reduction in blood pH. Acute forms (lasting minutes to several days) and chronic forms (lasting weeks to years) of the disorder can occur, for which the underlying cause/s and resulting adverse effects may differ. Acute forms of metabolic acidosis most frequently result from the overproduction of organic acids such as ketoacids or lactic acid; by contrast, chronic metabolic acidosis often reflects bicarbonate wasting and/or impaired renal acidification. The calculation of the serum anion gap, calculated as [Na(+)] - ([HCO(3)(-)] + [Cl(-)]), aids diagnosis by classifying the disorders into categories of normal (hyperchloremic) anion gap or elevated anion gap. These categories can overlap, however. Adverse effects of acute metabolic acidosis primarily include decreased cardiac output, arterial dilatation with hypotension, altered oxygen delivery, decreased ATP production, predisposition to arrhythmias, and impairment of the immune response. The main adverse effects of chronic metabolic acidosis are increased muscle degradation and abnormal bone metabolism. Using base to treat acute metabolic acidosis is controversial because of a lack of definitive benefit and because of potential complications. By contrast, the administration of base for the treatment of chronic metabolic acidosis is associated with improved cellular function and few complications. PMID- 20309000 TI - Autoimmune polyglandular syndromes. AB - The autoimmune polyglandular syndromes-a group of syndromes comprising a combination of endocrine and nonendocrine autoimmune diseases-differ in their component diseases and in the immunologic features of their pathogenesis. One of the three main syndromes, type 1 autoimmune polyglandular syndrome (APS-1), has a unique pathogenic mechanism owing to mutations in the autoimmune regulator (AIRE) gene, which results in the loss of central tolerance-a process by which developing T cells with potential reactivity for self-antigens are eliminated during early differentiation in the thymus. Patients with IPEX (immune dysfunction, polyendocrinopathy, enteropathy, X-linked) syndrome harbor mutations in the forkhead box P3 (FOXP3) gene in regulatory T cells, which leads to severe autoimmunity and immune deficiency. Although both of these disorders are rare, their well-defined mechanisms of disease provide a basis for the understanding of the more common condition, APS-2. In this syndrome, alleles of human leukocyte antigens (HLAs) determine the targeting of specific tissues by autoreactive T cells, which leads to organ-specific autoimmunity as a result of this loss of tolerance. Non-HLA genes also contribute to autoimmunity in APS-2 and, depending on the polymorphism, potentially predispose to a loss of tolerance or influence which organ is specifically targeted. This Review discusses the genetic basis of APS-1, APS-2 and IPEX syndrome, with an emphasis on the mechanisms of autoimmunity and presents currently available therapies to treat their underlying autoimmune disorders. PMID- 20309001 TI - Ischiatic pressure sores: our experience in coupling a split-muscle flap and a fasciocutaneous flap in a 'criss-cross' way. AB - STUDY DESIGN: Description of a technique and prospective follow-up study. OBJECTIVES: The aim of this study was to present our experience in the surgical treatment of ischial pressure sores, especially recurrence. SETTING: The Department of Plastic and Reconstructive Surgery and Spinal Injuries Unit, CTO Hospital, Rome, Italy. METHODS: From 1995 to 1997, the authors used in 12 consecutive paraplegic patients, who had a grade III or IV decubitus ulcer in the ischial area only, two different and independent flaps coupled together in a 'criss-cross' musculocutaneous flap: a split-muscle gluteus maximus flap and a rhomboid fasciocutaneous local flap. The average follow-up period was 3 years and 9 months. Details of the operative procedure are presented to prove that this criss-cross closure of the ischial pressure sore beneficial for patients with spinal cord injury. RESULTS: All flaps survived; recurrence of the decubitus ulcer occurred in one patient (8%). Pressure-sore-free survival after surgery was 20 months in the patient with recurrence and an average of 26 months in patients without recurrence. CONCLUSION: The results obtained confirm this procedure to be safe and useful. We believe this technique to be a valuable alternative for the reconstruction of primary or recurrent ischial pressure ulcers. PMID- 20309002 TI - Editorial note on: glucose tolerance and physical activity level in people with spinal cord injury. PMID- 20309003 TI - Civilian spinal cord injuries due to terror explosions. AB - STUDY DESIGN: Retrospective analysis of civilians with spinal cord injuries (SCIs) due to terror explosions. OBJECTIVES: To analyze and describe the clinical characteristics and rehabilitation outcomes of civilians with SCI due to explosions admitted for in-patient rehabilitation from 2000-2004. SETTING: SCI rehabilitation service, Tel Hashomer, Israel. METHODS: Retrospective chart review. Civilians with SCI due to terror-related gunshot wounds (GSWs) served as a control group. RESULTS: Eleven civilians with SCI caused by penetrating atypical foreign objects (PAFOs) and eight with GSWs were identified. The male-to female ratio was approximately 2:1. Foreign objects were present within the spinal canal in seven patients, causing bone injury without canal penetration in three, and one patient had both bone injury and canal penetration. The most common level of injury was thoracic. Seven had complete motor SCI. Three individuals improved in American Spinal Injury Association status: one individual improved from B to C (cervical); one from C to D (thoracic); and the third from D to E (lumbar). Despite the similar acute hospital length of stay and functional independence measure (FIM) scores on admission, the PAFO group had a shorter rehabilitation length of stay with higher FIM scores and higher FIM efficiency at discharge. CONCLUSIONS: Although the pathophysiology of PAFO blast injuries is similar to the high-velocity GSWs or the high-energy military munition injuries, better rehabilitation outcomes were seen, with slightly higher FIM efficiency and efficacy at discharge. This result is likely to be caused by less neurological tissue damage at impact. PMID- 20309004 TI - Impaired immune response to voluntary arm-crank ergometer exercise in patients with cervical spinal cord injury. AB - STUDY DESIGN: Non-randomized study. OBJECTIVE: The mechanism underlying exercise induced argumentation of natural killer cell cytotoxic activity (NKCA) in humans remains unclear. To address this, NKCA responses were studied during and after exercise in persons with cervical spinal cord injury (CSCI) and dysfunctional sympathetic nervous system. SETTING: Kibikogen Rehabilitation Center for Employment Injuries. METHODS: We examined the NKCA responses to 20-min arm-crank ergometer exercise at 60% of maximum oxygen consumption in eight persons with CSCI (between C6 and C7) and six able-bodied subjects. NKCA, adrenaline, and cortisol were measured before, immediately after exercise, 1 h after exercise, and 2 h after exercise. RESULTS: In able-bodied subjects, NKCA increased immediately after exercise (P<0.01) and then decreased to below the pre-exercise level 1 h after exercise, before recovering to the baseline level at 2 h after exercise. Plasma adrenaline concentrations increased significantly immediately after exercise (P<0.01) and returned to the baseline level 1 h after exercise. The plasma cortisol level did not change throughout the study. In contrast, NKCA, plasma concentrations of adrenaline, and cortisol did not change throughout the study in subjects with CSCI. CONCLUSION: In subjects with CSCI, the lack of response in NKCA throughout the experiment is probably mainly due to a dysfunctional sympathetic nervous system. PMID- 20309005 TI - Surgical treatment of post-traumatic syringomyelia. AB - STUDY DESIGN: A retrospective study. OBJECTIVES: To review the outcome of 40 patients with post-traumatic syringomyelia treated with laminectomy and reconstitution of the spinal subarachnoid channels. SETTING: Birmingham, United Kingdom. METHOD: A retrospective study of patients undergoing surgery between 1996 and 2007 was carried out. All 40 patients underwent a laminectomy with the creation of a cerebrospinal fluid (CSF) conduit. RESULTS: A total of 18 (1 in 2) patients had long-term stabilization of symptoms after laminectomy and creation of a CSF conduit alone. Later, 17 patients underwent supplementary procedures. Overall, surgical treatment resulted in 27(2 in 3) patients with continued stabilization of symptoms and 13 (1 in 3) experiencing worsening of symptoms in the long term (mean follow-up was 64 months). Radiological review at 6 months revealed a reduction in the size of the syrinx in 21 out of 33 (2 in 3) patients. CONCLUSIONS: Laminectomy for syringomyelia, with reconstruction of the spinal CSF channels alone, resulted in a reduction of syrinx size by 6 months, with half of all patients experiencing stabilization of symptoms in the long term. When additional techniques are taken into account, two in three of patients achieved long-term stabilization of symptoms. PMID- 20309006 TI - Tumor size and survival in breast cancer--a reappraisal. AB - The size of a breast cancer at diagnosis has conventionally been thought of as a fundamental and critical determinant of clinical outcome. However, the tendency of some subtypes of breast cancer to behave aggressively, despite being small (/= 0(1). The present analytic results are in good agreement with the numerical results of Bullock and Lipkis. PMID- 20309116 TI - Prism coupling selectivity in anisotropic uniaxial waveguide. AB - General coupling equations are derived describing field amplitude transfer from a prism to an anisotropic, uniaxial waveguide, having its optical axis in the plane of incidence. The influence of optical axis orientation on coupling efficiency and selectivity is discussed for a Gaussian incident beam. PMID- 20309117 TI - Gasdynamic light guide: high power density transmission measurements; errata. PMID- 20309118 TI - Patents. AB - 4,212,540; 4,218,138; 4,218,615; 4,221,459: 4,221,460: 4,221,463; 4,221,472; 4,221,483; 4,221,486; 4,222,630; 4,222,633; 4,222,634; 4,225,216; 4,225,786; 4,226,501. PMID- 20309119 TI - Selective excitation of parabolic-index optical fibers by Gaussian beams: comment. PMID- 20309120 TI - Lens design and local minima. AB - The widespread belief that local minima exist in the least squares lens-design error function is not confirmed by the Los Alamos Scientific Laboratory (LASL) optimization program. LASL finds the optimum-minimum region, which is characterized by small parameter gradients of similar size, small performance improvement per iteration, and many designs that give similar performance. Local minima and unique prescriptions have not been found in many-parameter problems. The reason for these absences is that image errors caused by a change in one parameter can be compensated by changes in the remaining parameters. False local minima have been found, and four cases are discussed. PMID- 20309121 TI - Cladded radially inhomogeneous sphere lenses. AB - When a radially inhomogeneous sphere is cladded with an additional refractive index medium, the spherical transverse aberration of a resultant lens is minimized in order to image a point light source in the diffraction-limited spot size for a lens a few millimeters in diameter with ~0.4 N.A. Examples of numerical data used in designing such sphere lenses are given for three different cases: imaging, Fourier transform, and optical disk reading. Various uses of these lenses are also envisioned for demonstrating their potential usefulness. PMID- 20309122 TI - Tomographic image reconstruction from limited projections using iterative revisions in image and transform spaces. AB - An iterative technique is proposed for improving the quality of reconstructions from projections when the number of projections is small or the angular range of projections is limited. The technique consists of transforming repeatedly between image and transform spaces and applying a priori object information at each iteration. The approach is a generalization of the Gerchberg-Papoulis algorithm, a technique for extrapolating in the Fourier domain by imposing a space-limiting constraint on the object in the spatial domain. A priori object data that may be applied, in addition to truncating the image beyond the known boundaries of the object, include limiting the maximum range of variation of the physical parameter being imaged. The results of computer simulations show clearly how the process of forcing the image to conform to a priori object data reduces artifacts arising from limited data available in the Fourier domain. PMID- 20309123 TI - Absolute distance measurements by variable wavelength interferometry. AB - This paper describes a laser interferometer which provides absolute distance measurements using tunable lasers. An active feedback loop system, in which the laser frequency is locked to the optical path length difference of the interferometer, is used to tune the laser wavelengths. If the two wavelengths are very close, electronic frequency counters can be used to measure the beat frequency between the two laser frequencies and thus to determine the optical path difference between the two legs of the interferometer. PMID- 20309124 TI - Interband transitions in aggregated copper films. AB - The optical properties of aggregated copper films have been studied in the spectral range from 200 to 1000 nm. Although it is well known that these films exhibit an anomalous absorption in the visible region attributed by many authors to collective oscillations of electrons in the particles forming the films, not much interest has been shown in the study of interband transitions occurring in these aggregated films. The results of the present work indicate that interband transitions are also found in copper in aggregated form, and that their effects cannot be ignored in the analysis of the optical properties of island films. PMID- 20309125 TI - Stability and astigmatic compensation analysis of five-mirror cavity for mode locked dye lasers. AB - A five-mirror cavity suitable for passively mode-locked dye lasers is analyzed and also modeled on the computer. Simple approaches for constructing a compensated cavity are shown. Experiments are performed confirming the theoretical results. PMID- 20309126 TI - Diffraction-limited geodesic lens: a search for substitute contours. AB - Diffraction-limited geodesic lens contours are compared with algebraic and transcendental contours. Curvature errors are analyzed for lenses between f/0.68 and f/10. It is shown that certain oblate ellipsoids of revolution closely approximate the diffraction-limited contour above f/3.0. Aberrations are analyzed, and a simple formula with tabulated constants provides a method for finding the closest approximation contour ellipse for a desired f/No. PMID- 20309127 TI - Coupling characteristics measurements between curved waveguides using a two-core fiber coupler. AB - Coupling characteristics between two curved waveguides are studied using a two core fiber. A tunable monochromatic light source is used to measure the wavelength dependence of the coupling efficiency. Measured values of the coupling efficiency agree well with theory. It is found that (1) the coupling efficiency can be changed from 0 to 1 by changing the radius of curvature, for example, from 100 mm to infinity in the measured coupler; and (2) when phase shift due to curvature sbeta/2R exceeds the coupling coefficient K, where s is the center-to center core separation, beta the propagation constant, and R the radius of curvature, coupling between the curved cores does not occur, and there is only the phase shift between the cores. PMID- 20309128 TI - Coupled wave analysis of obliquely incident waves in thin film gratings. AB - The problem of a guided wave obliquely incident on a grating etched in a thin film guide is considered. Two-dimensional coupled wave equations for the incident and reflected beams are derived for the cases of TE-TE, TE-TM, and TM-TM coupling. Two methods, a ray optic approximation and a coupled beam method, are proposed for the numerical solution of the coupled wave equations. Both methods are illustrated by a number of calculated examples. PMID- 20309129 TI - Calculations of stress-induced changes in the transverse refractive-index profile of optical fibers. AB - Changes in transverse refractive index induced by the photoelastic effect are calculated when an optical fiber is subjected to a uniformly applied diametral stress. For moderate values of the force per unit length applied to the fiber, we find that regions of comparable or higher refractive index than the core may be induced in the outer region of the fiber. Thus the stressed region is capable of acting as a mode converter that affects the transmission characteristics of the fiber and may enable coupling of energy in or out of the fiber. PMID- 20309130 TI - Pulse distortion in optical fibers with transverse offset splices. AB - A method for calculating the pulse distortion in a spliced multimode optical fiber vs transverse misalignment is presented. Measurements on two graded-index and one step-index fibers are shown. In graded-index fibers both theory and experiment show a rapid decrease of the rms pulse width for large offsets. For smaller offsets some discrepancies are observed. These are remedied to some extent by considering unequal mode excitation conditions. Different lengths of the two spliced sections are investigated as well. In the step-index case the experiments show no variation in the rms pulse width as predicted by the theory. PMID- 20309131 TI - Characterization of single-mode optical fiber filters. AB - The fabrication of narrowband highly reflecting filters in single-mode step-index fibers was reported recently by Hill et al. [Appl. Phys. Lett. 32, 647 (1978)]. The underlying effect on which these filters are based is a photoinduced refractive-index change in the GeO(2) used as a core dopant in SiO(2) fibers. A study is reported aimed at the characterization of such optical fiber filters. A theoretical model is developed, and relevant fiber parameters are determined through intercomparison with experiment. In this way, both the magnitude of the photoinduced index change and its dependence on the writing power coupled into the fiber are determined. PMID- 20309132 TI - Fluorescence profiling of single-mode optical fiber preforms. AB - A new nondestructive and noncontacting method to measure accurately the refractive-index profile of single-mode optical fiber preforms is presented. The method is based on the fact that a Ge-doped preform core fluoresces strongly when excited by UV radiation. The preform, which need not be index matched, is excited transversely to its axis by a He-Cd laser emitting at a wavelength of 325 nm. The intensity of the resulting fluorescence radiation is detected by a video camera and plotted giving the index distribution directly. The profiles so obtained in <1 min are in excellent agreement with those measured by interferometry and by the focusing method, thus providing a simple yet powerful alternative to those techniques. PMID- 20309133 TI - Measuring fiber connection loss using steady-state power distribution: a method. AB - This paper describes conditions for the reproducible measurement of optical fiber connection losses. The steady-state power distribution is characterized by the width of the far-field pattern (FFP). A method is proposed to determine the power distribution in the fiber from the measured FFP. Using this method, connection losses of graded-index fibers are calculated for various widths of the FFP. Calculated results are verified experimentally. The width of the FFP must be controlled to within an accuracy of 3% for a 0.05-dB reproducibility of the connection loss. Connection loss dependence on mismatch of fiber parameters is also calculated. Calculation shows that variations in core radius, numerical aperture, and index gradient have to be controlled to within 3%, 6%, and 0.3, respectively, for the same reproducibility. PMID- 20309134 TI - Relations between near-field and far-field intensities, radiance, and modal power distribution of multimode graded-index fibers. AB - A relation between the modal power distribution and the radiance at the fiber end face is derived. From this relation near-field and far-field intensities are expressed in terms of the modal power distribution. The relation for the far field intensity is discussed in detail for some special cases. PMID- 20309135 TI - Ultraviolet analysis of graded-index lightguide preforms. AB - The UV spectra of graded-index fiber-optic preforms have been studied using a technique in which annular masks of varying diameters are placed over the preforms. The collimated UV beam from a conventional absorption-spectrophotometer excites selected regions in the preform core, and the absorption spectra for the varying mask diameters are measured. With this technique and germania borosilicate and phosphosilicate (GeBSi and GePSi) preforms, a previously unresolved absorption band peaking at 330 nm was found and assigned to amorphous GeO(2). Measurements of the peak absorption coefficient were correlated with x ray fluorescence measurements of GeO(2) concentrations. Absorption associated with P(2)O(5) overlaps the GeO(2) absorption below ~320 nm. That is, between 305 and 320 nm, GePSi preforms absorb strongly while GeBSi preforms absorb weakly. This difference in absorption behavior combined with weak filtering properties of the UV-cured coating at lambda > 305 nm explains why coated GePSi fibers are more sensitive to UV damage than coated GeBSi fibers. PMID- 20309136 TI - Multimode fiber-optic hydrophone based on a schlieren technique. AB - A multimode fiber-optic hydrophone is described which is based upon a schlieren acoustooptic intensity modulation mechanism. Computer modeling of critical device parameters was experimentally verified and used to indicate ultimate attainable device performance. The device was shown to be able to detect the Knudsen noise level for frequencies up to 1 kHz, to have a dynamic range of 125 dB, to have an omnidirectional receiving response, and to be able to detect displacements as small as 3.4 x 10(-3) A. The device is not susceptible to phase noise, is relatively insensitive to static pressure head variations and is electrically passive. PMID- 20309137 TI - Performance of SIT vidicons when exposed to transient light signals. AB - A central phenomenon regarding the actual behavior of SIT vidicons under pulsed light operation is the capacitive lag. Although this physical effect has been known for years, many users are unaware of its consequences in photometric measurements of transient phenomena. This work describes different aspects of SIT tube behavior studied in conditions designed to simulate their operation when viewing a streak camera or channel plate intensifier phosphor screen. PMID- 20309138 TI - Continuous-readout extreme-ultraviolet airglow spectrometer. AB - A satellite-borne extreme-ultraviolet airglow spectrometer is described covering the 275-1420-A range with 8-A resolution. The spectrometer is of near normal incidence Rowland circle design and employs a holographically ruled concave grating. The detector is a microchannel plate with resistive anode providing a continuous readout of any 650-A ground-commandable subset of the total bandpass. This simultaneous wide spectral coverage results in a factor of 80 increase in sensitivity over a fixed exit slit design of equivalent resolution. PMID- 20309139 TI - X-ray monochromator designs based on extreme off-plane grating mountings. AB - Several monochromator designs are presented in which the beam is incident on the grating nearly parallel to the grooves. The efficiency of such mountings, when obeying the blaze condition, is much higher than that of classical arrangements. Because only the Snell's components of the angular coordinates are varied, this high efficiency is found over the complete wavelength range. With the designs described the wavelength region from 0.6 to 100 nm can be covered without interchanging gratings. For each wavelength the spectral resolution can be increased to ~10(4). Entrance and exit slit positions and the corresponding beam orientations are fixed. PMID- 20309140 TI - Deconvolution technique for line-of-sight optical scattering measurements in axisymmetric sprays. AB - A procedure has been developed for deconvoluting line-of-sight average measurements of droplet-size distribution and optical extinction into the actual radial variations of droplet-size distribution and droplet number density in axisymmetric sprays. Preconditioning the line-of-sight average data via spline smoothing was shown to be necessary to prevent a complete loss of accuracy in the central region of the spray. After preconditioning, uncertainties in the average data propagated about 1:1 into the deconvoluted results. Cumulative truncation errors for a worst-case analysis approached 15% in the central region of the spray. A sample analysis for a typical hollow-cone spray is presented. PMID- 20309141 TI - Radiative scattering cross sections: comparison of experiment and theory. AB - By comparing experimental and theoretical values of the radiative scattering cross sections of spherical particles over a wavelength range of 0.40-0.70 microm, both the scattering particle distribution function and concentration as well as the scattering coefficient are obtained. The experimental cross sections are derived from transmission data by using monodispersed polystyrene latex particles immersed in distilled water and a standard spectrophotometer. A discrete bimodal particle size distribution is used to account for coagulation. It is adjusted to yield the correct distribution function by making the difference between the experimental and theoretical cross section essentially constant with wavelength. The constant difference is proportional to the measurement error in the particle volume concentration and is easily eliminated by correcting the concentration. In addition, the scattering coefficient for the medium is obtained as a function of wavelength. PMID- 20309142 TI - Stratospheric trace constituent profile retrievals using laser heterodyne radiometer IR limb sensing spectra. AB - A retrieval technique for use with high resolution IR solar occultation limb sensing data is described for profiling stratospheric trace constituents. Remote measurement of CIO during sunset in the 24-45-km region with a 2-km height resolution is chosen as an example. Two types of instruments are considered: a laser heterodyne radiometer with line resolving spectral resolution and an interferometer spectrometer with a fixed slit width of 0.02 cm(-1). It is pointed out that a multichannel approach is necessary with the heterodyne instrument for improved retrieval accuracy. The error analysis indicates the relative sizes of instrument noise and other sources of error in the retrieval of altitude profiles with high (2-km) vertical resolution. PMID- 20309143 TI - Monostatic heterodyne lidar performance: the effect of the turbulent atmosphere. AB - The reduction in the SNR of a monostatic heterodyne lidar because of the presence of atmospheric refractive turbulence in the medium intervening between the lidar and the target was calculated. We find previous approximations made to perform the calculation, namely, independent refractive turbulence on outward bound and return paths and a quadratic form for the wave structure function, to be erroneous. An exact calculation shows that previous results overestimated signal degradation. PMID- 20309145 TI - Patterns of correlation of interferograms and Ronchigrams. PMID- 20309146 TI - Pulse compression by intracavity degenerate four-wave mixing. PMID- 20309144 TI - Comparison of reflectance with backscatter and absorption parameters for turbid waters. AB - The relation of reflectance to backscatter and absorption parameters is investigated for waters more turbid than those of previous investigations. Experimental data are examined for river waters in which beam attenuation values range from 8.9 to 18.9 m(_1) at 550 nm. Attenuation, absorption, backscatter, and irradiance reflectance spectral properties are presented for wavelengths between 450 and 800 nm. Comparisons of reflectance with backscatter to absorption ratio and backscatter with absorption plus backscatter ratio indicate that data for turbid waters do not fit linear or polynomial models which are presently available in the literature. PMID- 20309147 TI - Radio ffrequency-IR double resonance spectroscopy using a color center laser. PMID- 20309148 TI - Dichroic filters: a simple design. PMID- 20309149 TI - Echelle efficiencies: theory and experiment; comment. PMID- 20309150 TI - Echelle efficiencies: theory and experiment; author's reply to comment. PMID- 20309151 TI - Emissivity spectra of composite microscopic particles. PMID- 20309152 TI - Rayleigh scattering. PMID- 20309153 TI - Balloon-borne laser heterodyne radiometer for measurements of stratospheric trace species. AB - Remote measurements of a key stratospheric radical species, chlorine monoxide, have been made with a recently developed balloon-borne instrument: a laser heterodyne radiometer. The characteristics of this instrument, which facilitate its use for measurement of selected trace species in the stratosphere, are described here. The technique of solar occultation in the IR is used to provide the measurement data. This technique is briefly described to point out the high sensitivity and specificity which can be achieved when using a high spectral resolution instrument such as an IR heterodyne radiometer in this manner. PMID- 20309154 TI - Laser absorption spectrometer: remote measurement of tropospheric ozone. AB - The laser absorption spectrometer (LAS) is an airborne instrument able to perform remote measurement of trace atmospheric gases. The instrument uses a pair of carbon dioxide laser-heterodyne receiver systems that are directed downward from an airplane and determines gas concentration by the differential absorption method. Configured to measure tropospheric ozone, the LAS has been used in conjunction with another instrumented aircraft to test the accuracy of this method of measurement. A complete description of the instrument is presented, and the results of extensive flight testing are summarized. PMID- 20309155 TI - Optical pulse propagation through clouds. AB - The cloud impulse response (spatial and temporal) to optical pulse propagation has been measured. Experimental data are reported for the radiance function, pulse stretching, and (the first published) delay time. The results have been confirmed by Monte Carlo modeling. A geometric scattering model is presented explaining the temporal results for the test conditions. PMID- 20309156 TI - Target loop adaptive optics: thermal blooming correction. AB - To evaluate adaptive optics (AO) concepts for the correction of nonlinear atmospheric phenomena occurring in high energy laser beam propagation and to perform AO system trade offs, a simple, but reasonably accurate, model of the entire AO loop is required. Heretofore, no such model existed which takes into account the temporal response of the atmosphere and yet is simple enough to permit extensive system tradeoffs. We have developed such a model. Optimum thermal blooming correction dictates that the atmospheric response time must be accounted for properly, especially for strong blooming strength. Experimental verification of the above model was carried out using an argon-ion laser with an iodine blooming cell and a closed AO loop to provide corrections for tilt, focus, and astigmatism. Reasonable agreement between theory and experimental data was achieved. PMID- 20309157 TI - Optical communications through a dispersive medium: a performance bound for photocounting. AB - This paper considers the effects of pulse stretching and background radiation on a binary optical communication system with a photon counting detector. An idealized receiver processor is developed which provides a lower bound on the error probability that can be achieved by any realizable processor. A very simple approximation to the error probability is shown to be valid for intersymbol interference over more than about five-bit intervals. PMID- 20309158 TI - Offset local oscillator for cw laser Doppler anemometry. AB - Using two CO(2) lasers with one frequency-locked to the other, we have developed a simple heterodyne cw Doppler backscatter anemometer for remote sensing. The configuration as tested in a lidar application requires no additional optics or detector over a homodyne setup. Spectra of the vertical wind show an example of the results available from a simple heterodyne Doppler lidar with a threshold of 0.25 m sec(-1) and an uncertainty of +/-10% in the velocity estimate. PMID- 20309159 TI - Selection of fluorescence lidar operating parameters for SNR maximization. AB - Fluorescence lidar when applicable offers one of the most sensitive methods for measuring the concentration of trace constituents of the atmosphere. In the conduct of a fluorescence lidar experiment, one can control a number of parameters which can be used to optimize the SNR. In this paper the optimum division of laser pulses centered on and off the fluorescence excitation wavelength is calculated as a function of the ratio of the fluorescence signal strength to the strength of fluorescence from interfering species. For strong interference signals the time should be divided equally on and off the line. For strong fluorescence signals the time on line is proportional to the square root of the on-line off-line signal ratio. The optimization of the integration time for varying values of signal-to-background and signal-to-interference ratios, atmospheric attenuation, laser energy variations, background measurement time, and on-line off-line time division is also considered. PMID- 20309160 TI - Deviation-free Bragg cell frequency-shifting. AB - A method is described of applying a variable frequency-shift to a laser beam, by means of Bragg cells, in which the direction of the output diffracted beam is unaffected by the magnitude of the applied shift. Applications of the technique to reference-beam and Doppler-difference forms of laser anemometry are discussed together with methods of obtaining increased dynamic range. PMID- 20309161 TI - High gain optical detection with GaAs field effect transistors. AB - The photoresponse of GaAs field effect transistor (FET) optical detectors to optical intensity modulation signals of moderate frequency is investigated. High ac responsivity is available at frequencies of interest in optical communications: more than 6 A/W can be obtained up to 100 MHz, with a noise equivalent power of <10(-12) W/ radicalHz. The slope of the frequency response is dependent on the otpical bias power, an effect that can be attributed to traps. The GaAs FET optical detector complements the performance of available P-I-N and avalanche photodiode photodetectors for communications by providing high photoresponse at low bias voltages. PMID- 20309162 TI - Acoustooptic spectrum analysis of radar signals using an integrating photodetector array. AB - This paper examines the instantaneous Fourier power spectrum for different types of radar signals such as cw, pulse-modulated cw, and linear FM signals using an acoustooptic spectrum analyzer. The effects on the time-integrated output intensity distribution, due to the truncation of the propagating acoustic signal by the finite aperture width of the Bragg cell and the amplitude weighting on the signal, are also analyzed. Some experimental results on pulse-modulated cw and linear FM signals are presented and then compared to theory. PMID- 20309163 TI - Acoustooptic spectral estimation: a statistical analysis. AB - The power spectral density estimate obtained by an acoustooptic (AO) system is analyzed. We find that the variance of the estimate depends on the ratio T(2)/T(1), where T(1) is the aperture of the AO cell and T(2) is the integration time of the detector. PMID- 20309164 TI - Photoacoustic measurement of low-level absorptions in solids. AB - Small repetitively pulsed lasers can be used with a photoacoustic detection method to obtain linear absorption measurements on optical thin films with a 5 x 10(-5) sensitivity using an acoustic-coupling procedure and with a 1 x 10(-5) sensitivity using a liquid-transducer procedure. PMID- 20309166 TI - Two-dimensional modulation transfer functions of image scanning systems. AB - Image data processing based on optical scanning and digital reconstruction frequently ignores artifacts produced by the scanning process itself. Characterization of these artifacts by measurement of system modulation transfer function (MTF) using the traditional knife-edge scan technique produces only one section of the 2-D MTF, and interpretation of this as representative of the complete MTF may yield misleading re A theoretical analysis is presented which allows reconstruction of the complete 2-D MTF from a sequence of knife-edge measurements, and an experimental example is shown for the case of a vidicon camera based scanning system. PMID- 20309165 TI - Optical heterodyne profilometry. AB - A noncontact optical technique for the measurement of surface profile is described, which has a height sensitivity of the order of 1 A. It is based on a common path heterodyne interferometer in which two orthogonally polarized beams of slightly different frequency are focused on the surface to be measured. One focal point acts as a reference as the other point circularly scans the surface. The phase of the beat frequency of the interfering return beams is directly proportional to the surface height. The results of a surface measurement include graphical displays of the surface profile, autocovariance function, spectral density function, stability, and repeatability. Comparison with other instruments is also discussed. PMID- 20309167 TI - Thermal IR exitance model of a plant canopy. AB - A thermal IR exitance model of a plant canopy based on a mathematical abstraction of three horizontal layers of vegetation was developed. Canopy geometry within each layer is quantitatively described by the foliage and branch orientation distributions and number density. Given this geometric information for each layer and the driving meteorological variables, a system of energy budget equations was determined and solved for average layer temperatures. These estimated layer temperatures, together with the angular distributions of radiating elements, were used to calculate the emitted thermal IR radiation as a function of view angle above the canopy. The model was applied to a lodgepole pine (Pinus contorta) canopy over a diurnal cycle. Simulated vs measured radiometric average temperatures of the midcanopy layer corresponded within 2 degrees C. Simulation results suggested that canopy geometry can significantly influence the effective radiant temperature recorded at varying sensor view angles. PMID- 20309168 TI - Liquid crystal display device for total reflection switching with fluorescent dye addition. AB - Bias dependences for reflectivity curves were measured in the total reflection range for several liquid crystals, and orientation near the boundary was investigated. Incident angle dependences of the transient response for total reflection ON and OFF switching were measured. Fluorescent dye addition effects for total reflection switching were investigated. Using a mixture of the fluorescent dye (coumarin 6) and MBBA + BBCA, a novel display device for a wide viewing angle has been successfully demonstrated. PMID- 20309169 TI - Surface reflectance measurements in the ultraviolet from an airborne platform. Part 2. AB - The spectral and broadband reflectance of naturally occurring desert sand, black lava, White Sands, New Mexico gypsum sand, and snow cover is measured from a twin engine Cessna 402-series aircraft. The measurement system, fully described in Part 1 [D. D. Doda and A. E. S. Green, Appl. Opt. 19, 2140 (1980)], is computer controlled and electrically isolated from the aircraft. It consists of upward and downward looking hemispheric diffusers, filters, a rotating 90 degrees mirror, a focusing lens, and a double monochromator/PMT or a UV enhanced photodiode. Measurements are made at several altitudes enabling the empirical determination of the backscatter and attenuation effects on the reflectance. In addition these reflectance results along with those reported earlier for a pine forest, green farmland, the open ocean, and brown farmland are represented analytically. PMID- 20309170 TI - Optical reflectance: a sensitive nondestructive method for detecting surface damage in crystalline GaAs and other semiconductors. AB - Optical reflectance has been demonstrated to be a very sensitive nondestructive method to determine the degree of surface damage for crystalline germanium and silicon semiconductors. Application of this method to measure the surface quality of gallium arsenide (GaAs) is reported here. For GaAs, the optical reflectance at 5.1 eV can be used to determine the degree of surface damage, i.e., the surface quality. For a series of GaAs substrates polished with selected abrasives, the reflectance is shown to decrease with increasing size of the abrasive. As an independent method of determining the degree of surface damage, the photoluminescence spectrum of GaAs has been measured and correlated with the optical reflectance. Overall, the optical reflectance is shown to be a nondestructive, simple, fast, and sensitive measurement, which is readily adaptable to quality control inspection of GaAs and other III-V semiconductor surfaces. PMID- 20309171 TI - Vacuum ultraviolet Mach-Zehnder interferometer with CaF(2) optics. AB - A VUV Mach-Zehnder interferometer has been equipped with CaF(2) optics. To test these, the hook method was used to measure the oscillator strength of the 146.9610-nm (1)S(0)-(3)P(0)(1) line of atomic xenon. The result, f = 0.244 +/- 0.015, is in agreement with data obtained by other techniques. We conclude, as a result of this work, that application of our Mach-Zehnder interferometer to hook method measurements of oscillator strengths of lines with wavelengths longer than ~150 nm will be routine, but that such measurements below that wavelength limit must await development of more intense VUV continuum sources. PMID- 20309172 TI - Helmholtz resonator enhancement of photoacoustic signals. AB - A Helmholtz resonator attached to a nonresonant photoacoustic cell enhances the responsivity to trace gas absorption by as much as a factor of 15.3. A simple system model based on a lumped parameter approach predicts the experimentally determined resonance frequency f(0) within 6% for all five resonator volumes tried and gives a pressure amplitude response at resonance proportional to f(0)( 5/2), which is the approximate experimental dependence. Optimization of response based on the model shows a pressure amplitude dependence on a(1/2), the square root of the radius of the cylindrical tube connecting the cell and the resonator. PMID- 20309173 TI - Optics of flow cells for liquid chromatography. AB - The design and performance of flow cells and flow cell optics are discussed, with special consideration of the requirements of absorption measuring instruments used as detectors in liquid chromatography. The origins of refractive-index sensitivity and other flow-dependent disturbances and the role of the field and aperture stops in minimizing these effects are described. Equations are derived to show the interaction of optical parameters and flow cell dimensions, and conditions for optimum cell designs are presented. It is shown that under certain conditions, the acceptance of a flow cell varies directly with the square of the volume and inversely with the fourth power of the optical path length. The results of some experimental measurements are presented for various flow cell optical systems, and it is shown that sensitivity to changing refractive index of the solvent can be reduced to a small residual associated with reflection at solvent-window interfaces. PMID- 20309174 TI - Distortion of grating prisms, and their use in radial velocity determinations of astronomical objects with slitless field spectrographs. AB - The basic theory of off-axis distortion and dispersion errors of grating-prisms is given. it is used to determine steller radial velocities according to the reversion method with slitless grating-prism field spectrographs. PMID- 20309175 TI - Intensifier silicon vidicon spectrophotometer for line profile studies in astronomy. AB - The design and performance characteristics of a moderate dispersion spectrophotometer (Deltalambda ~ 0.1 nm) for astronomical observations are described. The spectrophotometer employs an intensifier silicon vidicon as detector. The operating characteristics of the detector have been evaluated and optimized. In astronomical use, the spectrupsilonophotometer is capable of recording line profiles of stars of m(upsilon) = 3.74 with a spectral resolution of 0.15 nm and SNR = 50 in an integration time of 10 sec when used with a 60-cm telescope. PMID- 20309176 TI - Photometric monitoring of hysteresis in solid-solid phase transformations. AB - The addition of a simple solid-state photometer to a standard polarizing microscope permits continuous monitoring of the optical path difference of birefringent crystals undergoing solid-solid phase transformations. This approach permits direct recording of phase transformation hysteresis loops for microscopic crystals. Such data offer advantages over conventional birefringence measurements for studies involving phase transformation dynamics. PMID- 20309177 TI - Optical analysis of point focus parabolic radiation concentrators. AB - A simple formalism is developed for analyzing the optical performance of point focus parabolic radiation concentrators. To account for off-axis aberrations of the parabola, an angular acceptance function is defined as that fraction of a beam of parallel radiation incident on the aperture that would reach the receiver if the optics were perfect. The radiation intercepted by the receiver of a real concentrator is obtained as a convolution of angular acceptance function, of optical error distribution, and of angular brightness distribution of the radiation source. For numerical calculations this method is more accurate and less time-consuming than the ray-tracing method. PMID- 20309178 TI - Chromatic aberration matching of the polychromatic optical transfer function. AB - To point out the danger of evaluating lenses on the basis of color-blind polychromatic OTFs, it has been shown that lenses with completely different chromatic aberrations can have the same polychromatic OTF. An analytical technique-chromatic aberration matching-is proposed that will ascertain the chromatic aberrations that are different and yet give the same polychromatic OTF for a specified spectral combination of the light source and the detector. A typical numerical example is given which supports the theory and the discussion. PMID- 20309179 TI - Intensity profile of outgoing beams from uniform and linearly tapered grating couplers. AB - Intensity distribution of outgoing beams from a uniform sinusoidal grating is investigated on the basis of first-order perturbation theory by dividing the grating region into short subsections. Intensity distribution of outgoing beams from a linearly tapered sinusoidal grating is also studied by considering it as a chain of uniform gratings with steplike amplitudes and using the results obtained for the uniform grating. The intensity profile of outgoing beams from a uniform grating coupler is theoretically verified to exhibit an extremely asymmetric shape and to differ considerably from the Gaussian shape laser beam usually employed as an incident beam in an input coupler, although this fact has been well recognized by people who have studied gratings. However, the output intensity beam profiles from the linearly tapered grating are found to approach a Gaussian shape similar to the profile of the incident beam. PMID- 20309180 TI - Equalization of dispersion in single-mode fibers. AB - Optical pulse equalization in single-mode fibers using positive and negative chromatic dispersion has been demonstrated by Lin et al. [Opt. Lett. 5, 476 (1980)]. In this paper, an earlier theory of pulse propagation in single-mode fibers is extended to the case of a tandem arrangement of N fibers with different dispersive properties. The theory includes first- and second-order dispersion. It is shown that, by using fibers with positive and negative chromatic dispersion, the first-order dispersion term cancels out on average. PMID- 20309181 TI - Ultraviolet-excited fluorescence in optical fibers and preforms. AB - Germanium-doped optical fibers and preforms are found to fluoresce at a wavelength near 420 nm when excited by UV radiation at a wavelength below 350 nm. The UV absorption spectrum of a preform sample was measured and found to exhibit a strong and relatively broad peak in the vicinity of 240 nm. Experimental results of the application of this effect to the refractive-index profiling of multimode optical fiber preforms is presented. In this application the preform is excited transversely to its axis by a He-Cd laser emitting at a wavelength of 325 nm. The resulting fluorescent radiation is detected by a video camera to give the concentration profile directly. The effects of boron and phosphorous dopants on the profile are also shown. PMID- 20309182 TI - Optical fiber end preparation: a new method for producing perpendicular fractures in glass fibers, coated-glass fibers, and plastic-clad fibers. AB - A new method for cutting optical fibers is presented. A smooth scratch, without any visible cracks and chipping, is circumferentially made around the complete periphery before the fiber is fractured by simple axial tension. Break angles of 0.5 degrees are easily obtained. Coated-glass fibers and plastic-clad fibers are cut properly for the first time owing to the novel scratching procedure. A compact tool is used to perform the required sequence of operations automatically. PMID- 20309183 TI - Branching elements for optical data buses. AB - Asymmetric 4-port couplers and star couplers with 60 ports for multimode fibers are described. The power variations in the output fibers over a -40-+120 degrees C temperature range are reported as is the insertion loss. The optimum output coupling required for minimum path attenuation is computed for a T-bus with symmetric and asymmetric couplers. PMID- 20309184 TI - Four definitions for the term emittance: errata. PMID- 20309185 TI - Fringe contrast in electronic speckle pattern interferometry. PMID- 20309186 TI - Distance measurement from a moving object based on speckle velocity detection. PMID- 20309187 TI - Optical alignment of a far-infrared Michelson interferometer. PMID- 20309188 TI - Polar display of a fractional order of optical interference. PMID- 20309189 TI - Testing concave aspheric surfaces: use of two crossed Babinet compensators. PMID- 20309190 TI - Easy way to find the sagitta depth. PMID- 20309191 TI - Mass spectrometry of ion-induced water clusters: an explanation of the IR continuum absorption; addenda. PMID- 20309192 TI - In situ separation of scattering and absorption in fluids. PMID- 20309193 TI - Optical absorption in thin slabs and spherical particles. PMID- 20309194 TI - Limits on the propagation constants of planar optical waveguide modes. PMID- 20309195 TI - Circular diffraction patterns from total internal reflection Raman-Nath modulators. PMID- 20309196 TI - Power fluctuations caused by laser beam wandering and shift. PMID- 20309197 TI - Splice loss and mode conversion in a multimode fiber: erratum. PMID- 20309198 TI - Accurate laser wavelength measurement with a precision two-beam scanning Michelson interferometer. AB - This paper gives the details of a precision two-beam scanning Michelson interferometer, designed and perfected for accurate comparison of an unknown laser wavelength and the precisely calibrated wavelength of a reference laser. An iodine Lamb-dip stabilized He-Ne 633-nm laser (calibrated with respect to a Kr standard) is used as the reference. The design incorporates features to minimize instrumental errors and the effect of fringe shifts caused by diffraction (in the IR). It is applied to accurate measurements of a stable CO(2) laser wavelength tuned to the centers of its various transitions. Measurements are done by simultaneous fringe counting and relative fringe-phase comparison at the two wavelengths using on-line data storage and processing with an electronic digital computer. The accuracy in the 10-microm region is several parts in 10(9) and is limited by correction for diffraction fringe shifts. Because of its low-Q and broadband operating characteristics, it can be applied to rapid accurate laser wavelength measurements over the entire wavelength range permitted by its transmitting optics. In the visible range where the diffraction correction is small, the interferometer can be used to perform measurements to within several parts in 10(11). The paper gives theoretical derivation of various diffraction corrections, the design and construction of the interferometer, the alignment procedures, detailed analysis of various error sources, and data processing. It also gives the details of a previously reported accurate measurement of the speed of light using the measured wavelength of the CO(2) R(14) line and its known frequency. PMID- 20309199 TI - Optical characterization of powders: the use of Mie theory and composite media models. AB - The measurement of the optical response of materials occurring as finely divided powders is difficult due to the complex interaction of the optical wave with the material. Guided by methods used to study the optical properties of composite media, we have developed experimental and theoretical techniques for characterizing the optical properties of powders. We have applied these techniques to two supported catalysts and have observed several optical effects arising from the very small particle size of these materials. PMID- 20309200 TI - Arc-acoustic interaction in rare gas flashlamps. AB - High frequency oscillations have been observed in rare gas flashlamp voltage and light output pulses. Experiments have shown that the frequency of the oscillations increases with the square root of the input electrical energy density. At fixed energy density input, the period of the oscillations increases linearly with the cylindrical lamp radius and with the square root of the atomic mass of the rare gas. These measured dependences suggest an acoustic generation mechanism with the gas temperature proportional to the input energy density. This interpretation allows a determination of the instantaneous gas temperature from the measured oscillation frequency. PMID- 20309201 TI - Multiplate resonant reflectors for the vacuum ultraviolet. AB - A multiplate resonant reflector has been designed, constructed, and used in the VUV as an output mirror for an Ar excimer laser. Details of the design calculations etc. are given. PMID- 20309202 TI - Efficiency and concentration ratio measurements of fluorescent solar concentrators using a xenon measurement system. AB - An indoor test stand for fluorescent planar concentrator-collectors (FPC) with a 1.6-kW xenon light source, irradiating a rectangular triangle (active area 400 cm(2)) with 82 mW cm(-2), and a typical homogeneity of +/-10% is described in detail. Conditions and definitions for the efficiency measurements are discussed, taking intensity and reflection effects into account. As an illustration FPC efficiency and concentration ratios are reported (best optical efficiency was 7.5% for a single-plate one-dye FPC), the influence of thickness variation is discussed, and an enhancement in solar cell efficiency is demonstrated. PMID- 20309203 TI - Zenith sky brightness and airglow emissions during the equatorial solar eclipse of 30 June 1973. AB - Experimental and calibration procedures used for photometric zenith measurements at Loiyengalani (2.75 degrees N, 36.6 degrees E) during the total solar eclipse of 30 June 1973 are described briefly. Comparison was made between sky brightness at wavelengths in the 3914-6300-A range during totality and morning twilight at Dar es Salaam. The twilight 3914- and 6300-A sky background ratio is sometimes close to the expected value for a pure Rayleigh molecular scattering process, but the corresponding ratio at eclipse mid-totality is about one-third this, indicating a shift toward the red consistent with an atmosphere containing aerosols. The zenith sky brightness at 5600 A was <1 kR/A, somewhat lower than has been observed at low latitudes during the past 50 years. Comparison of the 6300-A line emission rate of 1.4 +/- 0.6 kR with the Jan. 1974 Atmosphere Explorer satellite dayglow analysis suggests the main source of O((1)D) atoms during totality is by excitation of O((3)P) atoms in the lower thermosphere. About 1 kR of 5577 A was also observed, but the 5200-A emission was too low for reliable detection. An unexpectedly high 3914-A emission rate of at least 1 kR was apparent, the high rate being supported by observation at 4278 A. PMID- 20309204 TI - Atmospheric transmittance: improvement of LOWTRAN prediction by incorporating turbulence effects. AB - Using the mutual intensity function, we calculate the turbulence loss-effect and add such effects into LOWTRAN predictions and the experimental data. The turbulence corrections bring the Lowtran-calculated transmittance and the experimentally obtained transmittance into closer agreement with each other. PMID- 20309205 TI - AFGL atmospheric absorption line parameters compilation: 1980 version. AB - A new version of the AFGL atmospheric absorption line parameters compilation is now available. Major modifications since the last edition of 1978 include the updating of the strongest bands of water vapor, updated line positions for carbon dioxide, improved ozone parameters in the 5- and 10-microm regions, and updated and additional data for methane in the 3.5- and 7.7-microm regions. The atlas now contains over 159,000 rotational and vibration-rotation transitions from 0.3 to 17,880 cm(-1). PMID- 20309206 TI - Monotonic relationships between scattered powers and diameters in Lorenz-Mie theory for simultaneous velocimetry and sizing of single particles. AB - Monotonic relationships between scattered intensities and diameters in Lorenz-Mie theory are obtained with the aid of the SUPERMIDI computer program. The influence of the solid collection angle, scattered light, and of the real and imaginary parts of the complex refractive index on these relations is discussed. Results are given for typical opaque particles (aluminum) and transparent particles (glass). Emphasis is on the application of such relationships to simultaneous measurements of the velocity and the size of single particles embedded in flows. PMID- 20309207 TI - Passive remote smoke plume opacity sensing: a technique. AB - A new passive technique for the remote measurement of the visual opacity of plumes emerging from smokestacks is presented. It is based on the detection of the attenuation of the polarized component of Rayleigh-scattered background skylight as it traverses a smoke plume. A two-color difference measurement of the polarization of skylight through the plume is compared with a similar measurement of the unattenuated skylight adjacent to the plume. This method is independent of the intrinsic brightness of the plume resulting from the scattering of sunlight and cancels white-light polarization effects of plume-scattered radiation. A prototype instrument incorporating this method has been successfully field tested on an EPA smoke school generator and a power plant stack plume. PMID- 20309208 TI - Rapid inversion of limb radiance data using an emissivity growth approximation. AB - The time-consuming nature of limb relaxation-type inversion algorithms is due primarily to the numerous integrations over an absorption band to obtain forward radiance values with which to compare measured values. A new method has been devised for the quick and accurate (0.5% error) calculation of single gas broadband (~100-cm(-1)) limb radiance. The method uses a precalculated data base consisting of homogeneous path emissivity vs mass path data for a wide range of temperature and pressure. A 50-km altitude range, 1-km resolution, constituent inversion employing this method requires under 1 sec of computational time when run on modern computer hardware. The method does not rely upon a priori statistical knowledge. PMID- 20309209 TI - High sensitivity operation of discrete solid state detectors at 4 K. AB - Techniques are described to allow operation of discrete solid state detectors at 4 K with optimized junction field effect transistor (JFET) amplifiers. Three detector types cover the 0.6-4-mum spectral range with a noise equivalent power (NEP) of ~10(-16) Hz(-1/2) for two of the types and potential improvement to this performance for the third. Lower NEPs can be anticipated at longer IR wavelengths. PMID- 20309210 TI - Color contrast criteria in a guest-host mode liquid crystal display. AB - Color contrast in a liquid crystal display using dye dichroism is investigated experimentally. Nematic liquid crystal with a positive dielectric anisotropy is used as the host. Three kinds of merocyanine dye are used as the guest. Optimum solubility of the dye is decided, and its criteria, taking account of the color difference, is established. The color difference is given in the 1976 CIE (L*, a*, b*) color scale. The contrast ratio values show good correlation with observed estimated values, and the validity of the criteria is confirmed. PMID- 20309211 TI - Thermal action of laser irradiation in biological material monitored by egg-white coagulation. AB - Coagulation of egg white of Nd:YAG and CO(2) laser beams was filmed to illustrate the thermal effect of their radiation and the role of internal scattering caused by the increased structurization of the medium in its non-transparent phase, typical of practically all biological tissue. The purpose was a vivid demonstration of the range of necrosis attainable with these two lasers in surgical and endoscopic applications. PMID- 20309212 TI - Off-axis multipass amplifier as a large aperture driver stage for fusion lasers. AB - A multipass amplifier configuration is described which has potential as a large aperture, high gain driver stage for fusion laser systems. We avoid the present limitations of large aperture switches by using an off-angle geometry that does not require an optical switch. The saturated gain characteristics of this multipass amplifier are optimized numerically. Three potential problems are investigated experimentally, self-lasing, output beam quality, and amplified spontaneous emission output. The results indicate comparable cost for comparable performance to a linear chain, with some operational advantage for the multipass driver stage. PMID- 20309213 TI - Source flow effect on line shape. AB - The combined effect of mean and thermal particle motion on Doppler line shape is evaluated. Optical radiation transverse to the axis of a source flow with semi angle theta(e) is considered in the limit theta(2)(e) <<1. Expressions for gain and anomalous index of refraction are deduced in terms of radiation frequency and a parameter X(e) which characterizes the ratio of mean to thermal motion in the optical path direction. The decrement in cw chemical laser output power, due to transverse flow expansion, is briefly noted. PMID- 20309214 TI - Plasma-breakdown retropulse isolators for the infrared. AB - The design and performance of a passive plasma isolator for suppressing retropulses in high-power CO(2) laser-fusion systems are described. The device uses a gas-filled spatial filter designed to produce a plasma at the focal plane iris. General design criteria for these isolators are discussed, and the performance of a specific isolator is evaluated. For the unit tested, retropulse attenuations of 33 dB for focal plane intensities of 1.5 TW/cm(2) have been demonstrated. PMID- 20309215 TI - Effet de phase dans la dispersion de la puissance lumineuse des fibres optiques unimodales. AB - Pulse broadening calculations in monomode fibers do not include till now the phase variation of the coherent input field. Although it is correct to ignore this variation at wavelengths different from the zero material dispersion wavelength lambda(o), this effect must be taken into account for wavelengths nearly equal to lambda(o). We have found for silica-type fibers that if the relative source linewidth (Deltalambda(o))/lambdao is less than 10(-3), the phase effect largely dominates over important distances in the evaluation of the pulse broadening giving rise to a decrease of the r.m.s. output pulse width. Therefore, this effect must be relevant for the estimation of the maximum information capacity on monomode fibers. PMID- 20309216 TI - Mode properties of optical fibers with lossy components by the propagating beam method. AB - The theory of optical fibers has been concerned mainly with propagation in lossless waveguides. Although real fibers are composed of core materials with extremely small absorption coefficients, they may have claddings and jackets with substantially higher losses. These components can in turn selectively attenuate certain higher-order guided modes. The propagating beam method utilizes configuration space solutions to a scalar wave equation to generate the mode propagation constants and eigenfunctions for a general class of weakly guiding fibers. This method has now been generalized to treat fibers with absorbing components such as claddings and jackets. It is now possible to compute with this generalized method both the mode attenuation coefficients and mode eigenfunctions for such fibers. Results are given for planar and circularly symmetric waveguides with lossy claddings and jackets. PMID- 20309217 TI - Resonance of a dielectric cavity inside a fiber. AB - Resonance phenomena for a dielectric spherical cavity embedded inside a fiber waveguide are treated analytically. The interaction of fiber and scatterer fields is described in terms of an internal equation which is reduced into an infinite system of equations. The case of optically small but dense spheres is considered in detail. The resonance phenomena occurring for this case permit a decoupling procedure to be developed for the infinite system of equations. Analytic expressions are derived for the low-order mode central frequencies and quality factors. Numerical results are presented. PMID- 20309218 TI - Maser clocks. PMID- 20309219 TI - Computer simulation of the velocity matched gate. AB - Numerical calculations based on the coupled-wave equations have been carried out with various conditions for the operation of a velocity matched gate. The influences of velocity mismatch, impedance mismatch, and the attenuation of the modulation signal are studied. Our results show that velocity match is critical for very narrow gate. However, impedance mismatch is unimportant for the operation of such a gate. In fact, a standing wave gate can also generate short pulses provided the length of the device is much greater than the wavelength of the modulation signal. It is also shown that the side lobes of the pulses can be suppressed by tapering the coupling. PMID- 20309220 TI - Traveling wave amplitude modulator with 1-GHz bandwidth for coherent light optical communication. AB - Two electrooptic materials, deuterated cesium dihydrogen arsenate (D-CDA, CsD(2)AsO(4)) and lithium tanta-late (LiTaO(3)), are examined for the application of a traveling wave-type coherent light modulator. The main design goals are (a) low drive power of 4 W for 10% linear amplitude modulation; (b) +/-3-dB bandwidth of 1 GHz; and (c) 50-Omega impedance. Experimental performance based on theoretical expectations are presented for both materials. Using a microwave network analyzer, the results indicate that the D-CDA modulator gives better performance with a VSWR of 1.06 as compared with the LiTaO(3) modulator figure of 1.23. Direct Current contrast ratio measurements for D-CDA and LiTaO(3) were 50:1 and 20:1, respectively. PMID- 20309221 TI - Resolution and color blur of the one-step rainbow hologram. AB - From the point spread function and wavelength spread, the hologram image resolution and color blur for a one-step rainbow holographic process are analyzed. To achieve a higher image resolution and smaller degree of color blur, we proposed the insertion of a cylindrical lens in a one-step rainbow holographic process. We have shown that higher image resolution and a smaller degree of color blur can be obtained by the cylindrical lens technique. Experimental confirmations of the calculated results are also demonstrated. There is another advantage of the cylindrical lens technique, that is, a higher object beam irradiance, for which it relaxes the power requirement of the coherent source. PMID- 20309222 TI - Holographic filter that transforms a Gaussian into a uniform beam. AB - A simple method of constructing a holographic filter is described which transforms a Gaussian into a uniform beam and conserves 30% of the beam power. PMID- 20309223 TI - Multiplex holography for space-variant processing: a transfer function sampling approach. AB - Several techniques for the holographic representation of any bandlimited space variant system by spatially sampling the input plane and multiplexing the respective system transfer functions have been previously described. This paper describes an alternative multiplexing technique in which the transfer functions are sampled in the Fourier plane to produce the multiplexed holograms. Various techniques for generating multiple copies of the input function that are required during playback are considered. Experimental results using computer-multiplexed holograms are also presented. PMID- 20309224 TI - Defect measurements in digital optical disks. AB - A method of characterizing defects on an unrecorded optical disk is described. Information on the density of defects is obtained by analyzing the statistical distribution of the widths of the pulses obtained when playing back an unrecorded disk. It was shown that disk quality, as measured by bit error rates on actual recording, can be correlated with defect densities measured in this manner. The same method can also be used to characterize defects on uncoated substrates. It was demonstrated that defects on tellurium coated disks are largely the result of defects on the uncoated substrates. PMID- 20309225 TI - Linearity of image photon counting systems. AB - Image photon counting systems are limited in dynamic range by clumping of photon events which cannot be disentangled by the reduction processing. The loss of linearity is studied for overlapping of photon events of the same diameter. More realistic situations taking into account the pulse width distribution of the events and the limitations of the processing systems are also examined. In all cases, the dynamic range of image counting systems is limited to low counting rates. These systems require high resolution intensifiers and fast readouts of the target of the pickup tube. PMID- 20309227 TI - Patents patter. PMID- 20309226 TI - Simplified formula for the illuminance in an optical system. AB - A formula is derived for the illuminance at any surface in an optical system. By tracing a single ray one can compute the flux density at the image plane or any other position along the ray. The formula involves the ratio of the products of the principal curvatures of the wave front as it approaches each surface to products of the same quantities after the wave front is refracted at each surface. A procedure is presented for determining the required principal curvatures by generalizing the Coddington equations to multiple surfaces for both meridional and skew rays. Results are applicable to both spherical and aspherical surfaces. Since principal radii of curvature specify points on the caustic surfaces, the formula and computation procedure automatically yields the equations for caustic surfaces as a by-product. To illustrate the computation procedure the illuminance and caustic surfaces are derived for an aspherical singlet. PMID- 20309228 TI - Photoacoustic observation of thermal wave interference effects in thin samples. PMID- 20309229 TI - Dye lasers: triaxial and quadraxial flashlamp-pumped types compared. PMID- 20309231 TI - Passive multiplexing of digital fiber-optic sensors. PMID- 20309230 TI - Effect of laser diode spontaneous emission on IOSA operation. PMID- 20309233 TI - From the editor. PMID- 20309232 TI - Ocean-atmosphere interface: its influence on radiation. AB - The influence of the ocean-atmosphere interface on the radiance distribution in both the ocean and atmosphere is investigated. At visible wavelengths in the real ocean just below the surface, the downwelling radiance is a maximum within the critical angle and drops off by 1 or 2 orders of magnitude toward the horizon. The usual explanation that this is due to the sky radiation concentrated within the critical angle and the total internal reflection of the weak upward radiance at the ocean surface at angles outside the critical angle is too simplistic. There are two other important factors: (1) the atmosphere must have sufficient optical thickness so that appreciable sky (multiple scattered) radiation develops at all angles in the downward direction; (2) the water must have appreciable absorption so that the upwelling radiance just below the ocean surface is only a small fraction of the downwelling radiance entering the ocean. Examples show that, if either one of these conditions is not satisfied, an entirely different radiance distribution develops. The variation of the following quantities with depth is studied: radiance; vector and scalar irradiance; distribution function; reflectance; and heating rate. The radiance distribution in a homogeneous medium is compared with that in the same medium with an atmosphere-ocean interface at various depths within the medium. Most of the calculations are done for Rayleigh scattering centers, but some results are given for Mie-type scattering. PMID- 20309234 TI - Line parameters of methane from 2385 to 3200 cm(-1). AB - New line parameters of the methane spectrum have been incorporated in the AFGL compilation for the 2385-3200-cm(-1) region and were determined from data recorded at 0.01- and 0.02-cm(-1) resolution. Observed line positions and strengths are given for approximately 8076 absorptions with strengths >3.3 x 10( 24) cm/molecule (8.2 x 10(-5) cm(-2) atm(-1)). Lower state energies are given for 97% of the absorptions listed. Most of the lower states are determined through assignment of seven bands of (12)CH(4) (nu(1), nu(3), 2nu(2), nu(2) + nu(4), 2nu(4), nu(3) + nu(4) - nu(4) and nu(2) + nu(3) - nu(2)), four bands of (13)CH(4) (nu(3), 2nu(4), nu(2) + nu(4) and nu(3) + nu(4) - nu(4)), and three bands of CH(3)D (nu(1), nu(4), and 2nu(5)). A few of the lower state energies are determined experimentally from the data taken at cold sample temperatures. PMID- 20309235 TI - Ozone profiling from backscattered UV radiance measurements: a new procedure. AB - This paper presents a data analysis technique that has been developed to support a stratospheric ozone measurement and profiling program. The data consist of solar backscattered UV radiation monitored by a spacecraft. The output consists of ozone mixing ratio profiles complete with error bars throughout the atmosphere. The technique is based upon principles of nonlinear optimal estimation. It provides a number of desirable features that have not been available together in any previously constructed technique for the problem. Iteration on both radiation measurements and total ozone measurements is among these features. PMID- 20309236 TI - Statistical properties of He-Ne laser radiation reflected through a turbulent atmosphere. AB - Statistical properties of a He-Ne laser beam (0.63 microm) propagating through atmospheric folded paths of 1 and 12 km were investigated experimentally using direct and heterodyne detection. Measured scintillation histograms, power spectra, time autocorrelations, and phase fluctuations are reported. The turbulence parameters derived from the optical measurements were found to be in good agreement with those obtained from measurements of in situ temperature fluctuations. PMID- 20309237 TI - Telecentric optical system for observing daytime chemical releases at high altitudes. AB - A system to be used for the tracking of high altitude chemical releases in the presence of a bright daytime sky is described. The system uses telecentric optics, a tilting filter, a solid state image sensor, and a real time digital processor to produce the release image. Field test data are presented. PMID- 20309238 TI - Sparkle phenomenon. AB - Propagation of a laser beam of sufficiently high power density along a path contaminated by suspended particulate matter creates an impressive visible effect due to the burning of the particles. This effect, appropriately named sparkle, may seriously hamper attempts to utilize the beam path for receiving the low level object return signal required in the operation of certain closed loop control systems. This paper analyzes the sparkle phenomenon by examining the particle energy capture and loss mechanism and developing an event temperature history. Specifically, the observed event duration is explained in terms of the boiling point front velocity through the particle, and expressions for the particle motion in the beam are developed. PMID- 20309240 TI - Absorption cross-section maxima and minima in IR absorption bands of small ionic ellipsoidal particles. AB - Optical absorption cross section extrema can be investigated thoroughly for very small particles within the framework of the Rayleigh ellipsoid approximation. For an oriented ellipsoid with optical constants described by a one-oscillator Lorentz model, the frequency of maximum absorption lies between the transverse and longitudinal optical mode frequencies and depends on the particle shape and the surrounding medium; in general, the low frequency peaks are higher than the high frequency peaks. Absorption integrated over frequency for a single ellipsoid is independent of the damping constant. For randomly oriented ellipsoids, the integrated absolute maximum absorption is obtained for disks and the absolute minimum absorption for spheres. However, a sphere or any other ellipsoidal shape can be the greatest absorber at frequencies where surface modes are excited. Such surface modes are possible in the IR for particles of many common insulators: various alkali halides; oxides; carbonates; and silicates. PMID- 20309241 TI - Statistical properties of light reflected from a moderately rough surface scanned through a finite size aperture. AB - The probability density function P(I) of the integrated intensity I, reflected from a moderately rough surface, is computed correct to order (2pisigma/lambda)(2), where sigma is the rms of the surface roughness z(x), and lambda is the incident wavelength. By using the assumption that z(x) is a Gaussian random variable, we obtain P(I) as a function of the size of the detector aperture and the correlation length of the surface roughness. Numerical results and a comparison with previous works are given. PMID- 20309242 TI - High repetition rate frequency-doubled Nd:YAG laser for airborne bathymetry. AB - A flashlamp pumped frequency-doubled Nd:YAG laser producing 7-nsec 2.8-mJ pulses at 530 nm and 400 pps has been developed for use in airborne bathymetry. A flashlamp gas mixture of krypton and xenon provides efficient laser operation and rapid lamp recovery. Pulse transmission mode operation is used to achieve a narrow pulse width. Thermally induced lensing and birefringence in the rod are compensated for in the optical resonator. Rapid, high repetition rate Pockels cell switching is accomplished with a thyratron driver. A CD*A crystal cut for 85 degrees phase matching at 55 degrees C is used to provide high conversion efficiency second harmonic generation. PMID- 20309243 TI - Experimental determination of the incremental gain for a transit in a neodymium laser. AB - A method is described by which the power gain and axis intensity for a direct transit can be calculated on the basis of parameter measurements from the laser beam. The results obtained are used in the case of a neodymium laser. The measurements show that the power gain for a transit depends both on the diameter of the mode selector and the cavity length whereas the intensity gain depends only on the latter. The measured gains are smaller than the calculated ones on the basis of the plane wave approximation. PMID- 20309244 TI - Intracavity adaptive optics. 1: Astigmatism correction performance. AB - A detailed experimental study has been conducted on adaptive optical control methodologies inside a laser resonator. A comparison is presented of several optimization techniques using a multidither zonal coherent optical adaptive technique system within a laser resonator for the correction of astigmatism. A dramatic performance difference is observed when optimizing on beam quality compared with optimizing on power-in-the-bucket. Experimental data are also presented on proper selection criteria for dither frequencies when controlling phase front errors. The effects of hardware limitations and design considerations on the performance of the system are presented, and general conclusions and physical interpretations on the results are made when possible. PMID- 20309245 TI - Unified single-pass model of linewidths in the Hansch, single- and double-grating grazing-incidence dye lasers. AB - A N(2)-pumped dye laser is modeled as a spectrometer. An equivalent entrance/exit slit function is developed and used to calculate the single-pass linewidths for the Hansch, single- and double-grating grazing-incidence dye laser cavities. The results of these detailed calculations are expressed in grating-dependent terms to show the unity of the three solutions and to illustrate performance differences of the three cavities for any particular grating size, groove spacing, and order. PMID- 20309246 TI - Irradiation of biological specimens by a cw Ar(+) laser and temperature distributions. AB - Temperature measurements related to the interaction of the 5145-A line of a cw argon laser with in vivo whole biological specimens are presented, both in TEM(00), single frequency, and multimode, multifrequency operating conditions. A simple mathematical model for the evaluation of the temperature trends in a region outside the direct impact of the laser beam is also proposed. PMID- 20309247 TI - Two-mirror multipass absorption cell. AB - A multipass cell for absorption measurements with laser light is described. The number of passes is adjusted by variation of the distance of two parallel concave mirrors. The position and direction of the exit beam do not change when the path length is varied. A cell of 1-m length was used for infrared absorption measurements with an effective path length between 3 and 150 m. PMID- 20309248 TI - Nonlinear response of low-background extrinsic silicon detectors. 1: A phenomenological model. AB - Extrinsic photoconductive silicon detectors operated in the infrared at low background flux and high bias voltage respond nonlinearly to strongly modulated illumination. They can exhibit a dc nonlinear response even at low bias. We present a simple mathematical prescription for computing the output corresponding to a given input signal. This phenomenological model predicts results in reasonable agreement with measured response data for square wave input modulation. PMID- 20309249 TI - Optimum conditions in the attenuated total reflection technique. AB - In this paper the optimum condition for using the attenuated total reflection (ATR) technique is studied. In optimum conditions, the energy of an incident plane wave can be totally absorbed. The optimum condition can be realized by fabricating a localized thickness variation in the gap between a prism and a sample substrate with a point contact pressure. In the ATR technique, for example, the complex refractive index and the foil thickness of a thin metal foil, and the gap thickness are unknown parameters. To determine these unknown parameters, we prepared three prism coupling systems with different refractive indices. By this technique, we measured the complex refractive indices and the foil thicknesses of thin gold foils sputtered onto glass substrates, and the refractive index and the film thickness of a silica film sputtered onto a metal substrate. PMID- 20309250 TI - Variable birefringent beam splitter. AB - A sapphire disk is used as a variable birefringent beam splitter for the linearly polarized pump beam in an oscillator-amplifier dye laser system. Rotation of the disk varies the extent of retardation. The induced elliptical polarization results in a variable back surface reflectance between approximately 0.02-0.15 for the green spectral region. Reflectances are measured on two disks with different thicknesses and compared with an approximate model describing the reflectance as a function of angle of rotation of the disk. PMID- 20309251 TI - Dynamic optical tests of a high-speed polygon. AB - A dynamic optical deformation test for a high-speed polygon is described in which a laser beam is reflected off a rotating polygon and is focused on a pair of Ronchi rulings at 45 degrees to each other. The astigmatism and defocus terms of the deformation are measured and mapped over any one of the polygon facets. The relatively simple and sensitive setup is also used for testing pyramidal error, facet-to-facet angle error, and axis-to-facet interval deviations. PMID- 20309252 TI - Compact recording of the appearance of surfaces and thin films. AB - For improvement of optical surfaces and reflectivity enhancing films and for comparison with their appearance after use or testing, it is necessary to observe and record the nature of a surface or film with high resolution. Modifications of standard Twyman-Green and knife-edge testing methods are presented which meet this need. The appearance of flat surfaces of 40-mm diam can be preserved on a single photographic emulsion. Examples showing film defects due to reflectivity or phase changes with resolution of a few microns are presented. PMID- 20309253 TI - Graphical method to design multilayer phase retarders. AB - When multilayer reflectors are used at nonnormal incidence, the two planes of polarization generally have different phase shifts. This difference, known as phase retardance, depends on the multilayer design, the incidence angle, and the wavelength. Heretofore, the design of reflectors with specific phase retardance has been carried out by computer optimization except for the case of a single layer on a metal substrate. A graph of phase retardance D vs the average phase shift A as a function of layer thickness provides a means for visualization that is useful in reflector designs. A D-A graph predicts the phase properties of a reflector as a function of the index and thickness of an added layer. Graphs of phase retardance vs average phase for two different materials can be superposed to predict the composite performance of a multilayer reflector. This graphical technique is employed to design and analyze reflectors with specified phase retardance. PMID- 20309254 TI - Mechanisms of laser-induced failure in antireflection-coated LiNbO(3) crystals. AB - Substrate preparation before coating and coating cleanliness are the dominant factors affecting laser-induced damage to antireflection-coated LiNbO(3). Careful control of these factors resulted in an order of magnitude improvement in the damage threshold to 15-20 GW/cm(2) at 30 nsec across the entire surface. PMID- 20309255 TI - Nodular defects in dielectric multilayers and thick single layers. AB - The investigation of nodular defects in both thick dielectric single layers and multilayer systems by scanning electron microscopy (SEM) reveals the nodules to be of essentially the same shape no matter how many layers were deposited and what materials were used. The SEM micrographs of a thick LaF(3) layer used in IR coatings and of TiO(2)/SiO(2) multilayer systems are presented. Whereas the nodules in the thick fluoride layer are clearly caused by small spherical particles in an underlying layer of Ge, the cause is less obvious with the multilayer nodules. However, micrographs of uncoated glass substrate surfaces obtained by replicating films used for transmission electron microscopy as well as investigations by SEM and electron micro-probe techniques indicated that particular surface defects or contaminations of submicroscopic size act as the nuclei necessary for the formation of nodules. A growth model and possible measures to prevent nodular defects are discussed from a general point of view. PMID- 20309256 TI - Dielectric square bandpass design. AB - Two concepts new in square bandpass design make the design process easier and more systematic. One is the use of adjacent high-order rejection bands. The second is the use of effective index ratio. This paper extends the work of L. I. Epstein [J. Opt. Soc. Am. 42 806 (1952): "The Design of Optical Filters"] and A. Thelen [J. Opt. Soc. Am. 50 1533 (1966): "Equivalent Layers in Multilayer Filters"]. PMID- 20309257 TI - Mathematical methods in the synthesis and identification of thin film systems: errata. AB - The synthesis and identification of layered media is represented as an inverse problem for the wave equation or a related Schroedinger equation. Analytically it can be solved by using a relation between the reflection coefficient and the refractive-index profile, resulting from a Bremmer series solution of the wave equation. With a view to practical synthesis within a given system family three approaches are discussed: complete scanning by means of pattern recognition; investigation of a related Tschebyschev approximation problem; and application of quasi-linearization. PMID- 20309258 TI - Two-stage spatial filtering for diffraction pattern analysis. AB - The use of optical power spectrum analysis for feature detection and classification is often restricted by the superposition of the aperture spectrum. A spatial frequency filtering technique using a circular aperture and filters has been previously proposed to separate the object and aperture spectra. An adaptation of this technique using square apertures and an opaque cross spatial filter offers improved performance for some applications. Numerical calculations and experimental results are given comparing the two techniques. PMID- 20309259 TI - Propagation characteristics of single-mode evanescent field couplers. AB - The propagation of polarized light through a BOTTLE coupler has been investigated experimentally. Relative phase shifts for orthogonally polarized modes and the strength of coupling between these modes have been determined. These results have been related to elements in the transfer matrix for the coupler. The effect of polarization on the sensitivity of an interferometric sensor with a fiber coupler as the output beam splitter has also been investigated. PMID- 20309260 TI - Polarization-optical time domain reflectometry: a technique for the measurement of field distributions. AB - Consideration is given to a new optical fiber technique for the measurement of the spatial distribution of physical fields (e.g., magnetic field, electric field, temperature, mechanical stress): polarization-optical time domain reflectometry (POTDR). The technique relies upon the time resolution of light backscattered from a pulse propagating in a monomode optical fiber to measure the spatial distribution of the fiber's polarization properties. These properties are modified by the field under investigation. The technique appears feasible and could form the basis for a new measurement technology. PMID- 20309261 TI - Efficient conversion of light over a wide spectral range by four-photon mixing in a multimode graded-index fiber. AB - The efficient conversion of 1.06-mum radiation in a graded-index multimode optical fiber oscillator into a small number of spectral components propagating in specific modes of the fiber and falling in the spectral range spanning from the blue to 1.53 mum is reported. The effect is shown to result primarily from phase-matched four-photon mixing. The converted light is found to propagate as individual fiber modes which are identified. The wavelengths of the spectral components of the output of the oscillator are governed primarily by fiber geometry. Analysis of the results also indicates the presence and gives a measure of the fiber-core birefringence sensed by low-order modes of propagation of the graded-index multimode fibers we have studied. The efficiency of the oscillator source and the specific characteristic wavelengths available with common graded index fibers suggest several possible applications, which are discussed. PMID- 20309262 TI - EXOSAT x-ray imaging optics. AB - The European X-ray Observatory, EXOSAT, to be launched in 1981 will carry two Wolter I x-ray telescopes, each having a geometric area of ~100 cm(2). A qualification model of the Wolter I optics has been manufactured and extensively tested in optical and x-ray beams. The influence of manufacturing tolerances on the resolution of the optics is discussed, and mechanical and optical measurements of those deviations are presented. Finally, the x-ray imaging quality of the optics is presented, and the correlation with the achieved tolerances is shown. PMID- 20309263 TI - Bragg reflection concentrators for hard x-ray astronomy. AB - The use of parabolic concentrators with mosaic Bragg crystals as reflectors to the problems of hard x-ray source and cyclotron line detection is discussed. The primary application of the instrument is to detect the broad continuum of hard x ray sources at energies above ~5 keV where normal grazing incidence concentrators become inefficient. The sensitivity of the instrument is calculated for pyrolytic graphite and lithium fluoride reflectors. Sensitivity for sources with continuum fluxes 10(-3) Crab in the >20-keV energy range is possible for observing times of 10(4) to 10(5) sec. PMID- 20309264 TI - New Mauna Loa coronagraph systems. AB - A new set of instruments, consisting of two coronagraph systems, has been installed and is operating at the Mauna Loa Observing Station, Hawaii, operated by the High Altitude Observatory of Boulder, Colorado. The instruments are the 23 cm objective Mark III K-coronameter (K-III) system, a photoelectric instrument used to observe the inner solar corona from 1.2 R(0) to 2.2 R(0) and the 12.5-cm objective Prominence Monitor system used for the detection of H(alpha) limb activity. New features of the K-coronameter system include the use of achromatic wave plates for wide bandpass operation and linear diode array detectors. Raster scans of the coronal image are obtained in 1.5 min for a critical sampling scheme of 20-sec of arc resolution (10 x 10-sec of arc pixels) in the coronal p(B) image. This represents a 350 information gain factor for each detection channel when compared with the previous Mauna Loa K-coronameters. PMID- 20309265 TI - Complex spatial coherence function: its measurement by means of a phase-modulated shearing interferometer. AB - A stellar interferometer is proposed that has the following characteristics: parallel shear, phase modulation and detection, white light fringes, simplicity, and high mechanical stability. The interferometer developed is able to measure the complex coherence function of a star and distinguish it from most telescopic and atmospheric aberrations. This is achieved by detection of the fringes in the exit pupil, which is divided into small areas each less than a projected atmospheric isoplanatic patch. Then the phase-modulated fringes are detected independently in each area and summed incoherently. A description of a laboratory simulation is given. PMID- 20309266 TI - Lau effect: theory and experiment. AB - It was recently shown that coherence theory provides a simple and elegant means of interpreting and extending the Lau effect. The details of this analysis are presented along with experimental results which show good qualitative agreement with the predicted intensity distributions. In addition an unexpected intensity modulation is observed which is readily explained in terms of the present analysis. PMID- 20309267 TI - Optical properties of metals. PMID- 20309269 TI - Light trap of high performance and simple construction. PMID- 20309268 TI - Lidar survey of the post Mt. St. Helens stratospheric aerosol at Haute Provence Observatory. PMID- 20309270 TI - Azimuthal radiometric temperature measurements of wheat canopies. PMID- 20309271 TI - Scattering calculations using a microcomputer. PMID- 20309272 TI - Time-average laser specklegram of plate vibration using multiaperture recording. PMID- 20309273 TI - Effective optical constants of anisotropic materials: erratum. PMID- 20309274 TI - Patents. AB - 4,004,093; 4,064,535; 4,160,162; 4,206,969; 4,209,224; 4,210,400; 4,230,397; 4,230,398; 4,230,941; 4,230,942; 4,231,636; 4,231,637; 4,232,941; 4,232,942; 4,232,943; 4,232,944; 4,232,945; 4,233,107; 4,233,501; 4,235,518; 4,235,519; 4,235,520; 4,235,521; 4,236,789; 4,237,550. PMID- 20309275 TI - Aspheric potpourri. AB - This paper pursues further applications of the geometric design procedures described previously [L. Mertz, Appl. Opt. 18, 4182 (1979)]. One novel system with a large spherical main mirror provides an almost ideal searchlight solution with numerous potential applications. In addition, several new forms of coma correctors are developed for application with the Arecibo-style telescope configuration. PMID- 20309276 TI - Balloon-borne stratospheric far-IR spectral absorption measurements: the design of a solar telescope and high-resolution Michelson interferometer combination. AB - The design, construction, and performance of a combined solar telescope and Michelson interferometer for balloon-borne stratospheric far-IR absorption studies is discussed in terms of the relevant parameters and precautions necessary to obtain high resolution radiometrically calibrated spectra of the stratosphere between 20 and 100 cm(-1). Preliminary data are presented to indicate that the system performed as designed and provided constituent concentration values for H(2)O and O(3) from measurements of strong absorption lines in this spectrum. PMID- 20309277 TI - Self-calibrating technique for beam divergence measurements of cw and pulsed lasers. AB - A convenient method to measure beam divergence of laser beams is described. The apparatus is compact and accurate due to the use of a telescope to focus the beam. Incorporation of a Fabry-Perot etalon permits focusing and in situ calibration. Measurement of single-pulse beam divergence is performed with a CCTV system which includes a video tape recorder. PMID- 20309278 TI - Light absorption by airborne aerosols: comparison of integrating plate and spectrophone techniques. AB - An excellent correlation between the integrating plate (IP) and the photoacoustic methods for measuring aerosol light absorption has been found for airborne graphitic carbon in diesel vehicle exhaust. However, the regression coefficient depends on the orientation of the Teflon membrane filter during the IP analysis. With the collected particulates between the filter and the integrating plate, the IP response is 1.85 times that for the filter reversed. In either case the response ratio of the IP method to the photoacoustic method is >1.0, i.e., 2.43 vs 1.30. The IP calibration is also probably dependent on the nature of the filter medium. PMID- 20309279 TI - OH rotational temperature from two-line laser-excited fluorescence. AB - A two-line laser-excited fluorescence technique has been developed to measure the rotational temperature of the OH molecule. This technique eliminates problems encountered in the application of other laser fluorescence methods for measuring the OH temperature in combustion environments, such as fluorescence trapping, nonequilibrium excited state population, spectral bandwidth sensitivity, and quenching. The technique consists of exciting a specific rotational level of the OH molecule in the A(2)Sigma (upsilon' = 0) excited state from two different rotational levels in the X(2)Pi(upsilon'' = 0) ground state using a tunable dye laser and monitoring the broadband fluorescence. An example of the implementation of this technique in an atmospheric pressure methane-air flat flame is included. The possible application of this technique in turbulent combustion is also evaluated. PMID- 20309280 TI - Fluorescence of mixed powder samples: a six-flux theory. AB - A six-flux theory is derived for the diffuse reflectance and fluorescence of mixed powder samples of various shades of gray. One component of the powder is assumed to be fluorescent, with nonoverlapping excitation and emission bands. For symmetrical normal illumination and isotropic scattering, the six-flux reflectance reduces exactly to the Kubelka-Munk (two-flux) expression. Measurements of the fluorescence of a series of silica-silicon carbide-calcium tungstate mixed powder samples, which were found to vary over a range of 60:1, correlate well with the six-flux theory over the full range, whereas a two-flux theory is satisfactory only at high sample reflectances. PMID- 20309281 TI - Absolute spectroradiometric and photometric scales based on an electrically calibrated pyroelectric radiometer. AB - An absolute spectroradiometric scale has been developed based on an electrically calibrated absolute detector and silicon detector-interference filter combination. Using the recently adopted definition of the photometric base unit, the candela, the absolute spectroradiometric scale was used to realize a photometric scale, i.e., to calibrate incandescent lamps as luminous intensity standards. These new scales were compared with existing standards and were found to agree to better than 1%. PMID- 20309282 TI - Broadband single-pulse CARS spectra in a fired internal combustion engine. AB - The first known broadband single-pulse coherent anti-Stokes Raman scattering (CARS) measurements within the cylinder of a firing internal combustion engine are reported. Postcombustion temperature and carbon monoxide concentration are probed with 1-mm(3) spatial resolution and 10-nsec temporal resolution. Space- and time-resolved measurements, as presented here, are shown to be necessary for the study of fluctuating systems such as engines. PMID- 20309283 TI - Quantitative ATR spectroscopy: some basic considerations. AB - A comprehensive treatment of ATR spectra on the basis of the Lorentz-Lorenz law and Fresnel equations is given. The standard equation for the effective thickness is redefined showing how the lossy case deviates from the lossless case. A matrix effect due to the influence of the real part of the refractive index within an absorption band is demonstrated theoretically as well as experimentally. The concentration of a nonab-sorbing solute sample, i.e., glucose, is determined by ATR spectroscopy near the critical angle. PMID- 20309284 TI - Absolute tracer dye concentration using airborne laser-induced water Raman backscatter. AB - Reported here for the first time is the use of simultaneous airborne laser induced dye fluorescence and the 3400-cm(-1) OH-stretch water Raman backscatter spectra to yield the absolute concentration of an ocean-dispersed tracer dye. Using a straightforward theoretical model, the concentration is calculated by numerically comparing the airborne laser-induced fluorescence and Raman backscatter spectra to similar laboratory data for a known dye concentration measured under comparable environmental and instrumental conditions. The dye is assumed to be uniformly mixed throughout the water column together with other interfering, fluorescent, organic matter. A minimum detectable integrated water column dye concentration of approximately 2 ppb by weight as limited by background and instrument noise is obtained. A dye concentration contour map produced from the conical scan lidar data is given. PMID- 20309285 TI - Decay kinetics of (4)F(3/2) fluorescence of Nd(+3) in YAG at room temperature. AB - By means of localized time constant measurements, the fluorescent behavior for the principal transition of YAG:Nd emanating from the (4)F(3/2) state has been analyzed at room temperature as a function of concentration. It is found that the overall decay process is the superposition of multiexponential components over the concentration range of 0.9-1.6 at. % of Nd. The dependence of decay rate on excitation intensity was examined to register monomolecular kinetics for the case associated with each exponential decay process. From these results it is predicted that the YAG:Nd crystals are inhomogeneously broadened in nature similar to glass. PMID- 20309286 TI - Thermal distortion modeling of mirrors based on experimental data. AB - Mirrors are modeled to match test results from the Thermal Distortion Test Facility (TDTF) at Kirtland AFB, Albuquerque, N.M. The model allows distortions resulting from realistic beam profiles to be accurately calculated from a closed form five-parameter equation. The basic modeling concepts as well as the model's capabilities are discussed. A comparison of model distortion predictions with observed distortions resulting from a high-energy laser beam is made. PMID- 20309287 TI - Coupled optical resonators for the enhancement of laser intracavity power. AB - A double-cavity optical configuration designed to maximize the power available from cw lasers is reported. A passive supplementary cavity is strongly coupled to the main active laser cavity. It is shown theoretically that higher powers are available inside the passive cavity than those achievable by operating the same laser in a two-mirror configuration designed for optimum coupling. Furthermore, the power inside the passive cavity is equal to or greater than the useful circulating power in the two-mirror configuration. Key aspects of the theory are verified with a high power cw argon laser. PMID- 20309288 TI - Interlaboratory measurement comparison to determine the radiation angle (N.A.) of graded-index optical fibers. AB - A procedure for determining the radiation angle (N.A.) of graded-index optical fibers was tested by an inter-laboratory measurement comparison among six fiber manufacturers and the National Bureau of Standards (NBS). Radiation angle was determined using the 5% intensity points on an exit far-field radiation pattern. Measurements on five fibers representing low-to-high N.A. values show standard deviations of 2.9, 2.4, 2.0, 1.5, and 0.9%. The overall average, 2.0%, is close to the one standard deviation measurement precision reported by most participants. PMID- 20309289 TI - Bending losses in hollow and dielectric tube leaky waveguides. AB - A general method is presented of evaluating bending losses in hollow-core waveguides; analytic expressions are obtained for metallic hollow, dielectric hollow, and tube leaky waveguides on the basis of the 2-D slab waveguide model. Numerical examples are given for waveguides made of different kinds of metals, oxide, and dielectric materials at 10.6 microm. It is shown that the dielectric tube leaky waveguide can be bent with a small bending radius compared with a metallic hollow waveguide when the guide material is appropriately selected. PMID- 20309290 TI - Calculation of photopolymerization energy required for optical fiber coating. AB - The UV flux density required for photopolymerization is calculated, primarily based on an estimation of the overall system efficiency and the activation energy of the photoinitiator added to the prepolymer solution. We found that there is a linear relationship between the flux density and coating speed. The experimental results support the relation. Furthermore, it is noted that full curing has been achieved at speeds >5 m/sec with the 10-kW output power. The 10-kW system delivers 1.5 kW of UV power in the 300-400-nm spectral range. PMID- 20309291 TI - Linear Fresnel lens with polar tracking. AB - The performance of coma and color corrected linear Fresnel lenses for solar concentration is evaluated for use in polar tracking systems. Effective concentrations of up to 90 at 75% efficiency were obtained. PMID- 20309292 TI - Digital holographic interferometry of convective heat transport. AB - Real-time holographic interferometry has been used to study the convective heat transport in a flat plate solar collector. The analysis and interpretation of the interferograms using digital techniques are discussed. This study aims to develop an automated digital process for interference pattern analysis, and thus special attention is given to those optical and physical aspects that are relevant to this goal. This includes the structural systematics of the fringes, noise due to spurious optical effects, and the accuracy of digitized optical signals. Some experimental results on automated analysis of interferograms will be discussed. PMID- 20309293 TI - Far-IR optical properties of freestanding and dielectrically backed metal meshes. AB - The optical properties of freestanding and dielectrically backed inductive metal meshes are investigated in the far IR spectral regime. The most pronounced effect of the substrate is to cause a shift in the diffraction edge to longer wavelengths by a factor equal to the substrate index of refraction. Various theoretical models are reviewed and tested with the main result being that only the microwave based waveguide-array model successfully predicts the freestanding and dielectrically back optical features in and around the diffraction edge. A simplified version of this model is presented and shown to be adequate for describing the majority of the spectral features. The backed meshes are then characterized in terms of mirror quality for use in optically pumped far IR lasers. PMID- 20309294 TI - Determination of optical constants of absorbing materials using transmission and reflection of thin films on partially metallized substrates: analysis of the new (T,R(m)) technique. AB - A new accurate technique for determining the optical constants of thin absorbing films is presented. The configuration used includes a conventional spectrophotometer and a transparent substrate, half of which is covered with an opaque highly reflecting metal layer prior to the deposition of the film to be studied. The normal incidence transmission T of the thin film on the transparent substrate is then combined with a measurement of the near normal reflection R(m) of the same film on the metal covered part of the substrate. The combination (T,R(m)) yields an accurate and experimentally simple technique for determining the optical constants of thin films. A detailed evaluation of the accuracy of the extracted optical constants n and k of the thin film is obtained from numerical computations using realistic assumptions of various experimental uncertainties. Comparison with conventional techniques shows a greatly improved accuracy of the new technique. PMID- 20309295 TI - Optical activities in industry. PMID- 20309296 TI - Soft x-ray propagation on cylindrical polystyrene surface by successive grazing reflections. PMID- 20309298 TI - Space-bandwidth product for the Mellin transform. PMID- 20309297 TI - Precise periodicity control in the fabrication of holographic gratings. PMID- 20309299 TI - Deuterium lamp based monochromator calibration extended down to 115 nm. PMID- 20309300 TI - Extinction coefficients calculated from aerosol spectra measured in a convective marine layer with stratus. PMID- 20309301 TI - Deviation-free Bragg cell frequency-shifting: erratum. PMID- 20309302 TI - Laser absorption spectrometer: remote measurement of tropospheric ozone; erratum. PMID- 20309303 TI - Selective detection of uranium by laser-induced fluorescence: a potential remote sensing technique. 1: Optical characteristics of uranyl geologic targets. AB - The remote sensing of laser-induced uranyl ion fluorescence is examined as a potential indicator of uranium occurring in geologic materials at the earth's surface. The lifetime and brightness of the fluorescence from a wide variety of rocks, minerals, and soils are reported. The distinctive characteristics of uranyl ion absorption and fluorescence were observed in diverse geologic materials such as chalcedonies and opals containing 15-3000 ppm of uranium and in surface coatings of uranyl minerals such as metaautunite, liebigite, and an dersonite. The conditions which permit the excitation and selective detection of uranyl ion fluorescence from such targets are described. PMID- 20309304 TI - Selective detection of uranium by laser-induced fluorescence: a potential remote sensing technique. 2: Experimental assessment of the remote sensing of uranyl geologic targets. AB - An analysis is presented of a method to detect selectively uranyl ion fluorescence from geologic targets. Limitations to the sensitivity which are imposed by system parameters and noise sources are discussed. A ground-based laser system designed and constructed as part of this study is described, and data obtained with this system are presented. Finally the operating criteria of a conceptual airborne system for regional mapping of uranyl fluorescence anomalies are considered. PMID- 20309305 TI - Information content of optical data with respect to aerosol properties: numerical studies with a randomized minimization-search-technique inversion algorithm. AB - The information content of a set of optical data with respect to the particle size distribution is discussed in a numerical study. We show how the kernels of the integral equation relating size distribution and optical properties can be used to determine the particle size range in which an inversion of the size distribution is possible. We present an iterative least squares fit algorithm allowing the inversion of optical data to yield a histogram distribution for the particle size distribution. We discuss the uniqueness and stability of the solutions in relation to the range of radii and in relation to the number of histogram columns by means of synthetic data calculated via Mie theory. PMID- 20309306 TI - Infrared water vapor continuum absorption: equilibria of ions and neutral water clusters. AB - The temperature dependence of (C(o)(s))lambda, the self-broadening coefficient for the water vapor continuum absorption at wavelength lambda, can be modeled by the equilibrium ion product of water which is tabulated widely in physics texts and handbooks. A theoretical basis for this modeling is developed from water cluster theory, and it is shown that experimental values of (C(o)(s))lambda. could be seriously in error, especially at high temperatures, if the saturation ratio (fractional RH) of water vapor is not taken into account by the experimenter for reasons other than normalization of the coefficient for partial pressure of the sample. An explanation is suggested for the departure of (C(o)(s))lambda from the usual negative dependence on increasing water vapor temperature in some experiments. Figures are given showing equilibrium sizes and populations of neutral water clusters and ions in water vapor as functions of humidity and temperature, based in part on data of Bignell and other workers. PMID- 20309307 TI - AFGL trace gas compilation: 1980 version. AB - A new edition of the AFGL trace gas compilation is now available. Absorption line parameters of positions, intensities, and halfwidths are given for the major bands of thirteen gases covering the spectral region from 0 to 10,000 cm(-1). In addition to updating the original gases (NO, SO(2), NO(2), and NH(3)), the molecules HNO(3), OH, HF, HC1, HBr, HI, CIO, OCS, and H(2)CO have been added to the compilation. The sources for the additions and modifications are described. PMID- 20309308 TI - Vacuum-pipeless laser earth strainmeter. AB - A vacuum-pipeless laser strainmeter has been designed, tested, and is described. The strainmeter has a compensator for the change of the refractive index of air which is determined by Edlen's formula using measured values of atmospheric pressure and temperature. The effect of air-condition change was compensated by the compensator, and residual of the effect was less than +/-5 x 10(-9) for 75 h. The strainmeter has successfully recorded solid tidal strains. PMID- 20309309 TI - Photothermal deflection spectroscopy and detection. AB - The theory for a sensitive spectroscopy based on the photothermal deflection of a laser beam is developed. We consider cw and pulsed cases of both transverse and collinear photothermal deflection spectroscopy for solids, liquids, gases, and thin films. The predictions of the theory are experimentally verified, its implications for imaging and microscopy are given, and the sources of noise are analyzed. The sensitivity and versatility of photothermal deflection spectroscopy are compared with thermal lensing and photoacoustic spectroscopy. PMID- 20309310 TI - Light-beat measurements of second-order space-time correlation in the transmittance of a fluctuating medium. AB - A method is proposed for measurements of the second-order space-time correlation in the transmittance of a given fluctuating medium. Three kinds of light-beat photocurrent are produced by the use of some optical polarization components and two photodetectors. Correlational processing of these currents by an electronic correlator offers two correlation outputs in phase quadrature from which the correlation of concern can be constructed. The measurements of its modulus and phase are assured by simulation experiments using a thermally turbulent atmosphere in an optical heterodyne interferometer. PMID- 20309311 TI - Vacuum UV and soft x-ray optical emissions from electron impact on metals. AB - Spectrograms from 2200 to 20 A of optical emissions produced by a simple lamp using fast (3-10-keV) electron impact on tungsten and tantalum targets are presented. The lamp dissipated up to 5 kW/cm(2) on the target surface, simultaneously cleaning the surface and generating bremsstrahlung in the soft x ray region with 3-keV electron impact and longer wavelength transition radiation at the higher energy. In both the bremsstrahlung and transition radiation modes, the lamp emissions were of sufficient strength and reproducibility to qualify the two mechanisms as potential processes for use in a secondary standard light source. Calculated spectral distributions of transition radiation for normally incident electrons on tungsten, tantalum, and aluminum targets, with a viewing direction 45 degrees from the normal, are also shown. PMID- 20309312 TI - Near millimeter wave bandpass filters. AB - The properties of bandpass filters for broadband photometry are reported in the 3 12-cm(-1) frequency range. The filters are based on a combination of capacitive grids deposited on thick Mylar substrates and are designed to have very high out of-band rejection. Low frequencies are blocked by a thick grill that consists of a hexagonal grid of circular holes in a thick metal plate. PMID- 20309313 TI - Fundamentals of plasma physics. By v. E. Golant, a. P. Zhilinsky, and I. E. Sakharov. PMID- 20309314 TI - Far-infrared bandpass filters from cross-shaped grids. AB - The optical transmission characteristics of electroformed metal grids with inductive and capacitive cross patterns have been investigated in the far infrared spectral region. The transmission characteristics of one-and two-grid devices are represented by transmission line theory parameters. Results are used to suggest construction guidelines for two-grid bandpass filters. PMID- 20309315 TI - Particle size measurements using an optical variable-frequency-grid technique. AB - A fringe visibility method for sizing particles 10 microm and larger has been developed. As the image of a particle scans across a variable frequency grid, the transmitted light signal oscillates with varying visibility. The visibility goes through a null at a well-defined point where the particle diameter approximates the local grid spacing. Several optical arrangements implementing the variable frequency grid technique have been tested. Using classified alumina and pulverized coal particles we obtained good agreement between size distributions measured by this technique and those from a commercial off-line analyzer. However, our optical arrangement and signal processing techniques require further development to reduce them to practice. PMID- 20309316 TI - Tandem multipass Fabry-Perot interferometer for Brillouin scattering. AB - A new design of a plane mirror Fabry-Perot interferometer with the mirror blanks freely supported by horizontal rings is described. Special attention is paid to the surface flatness and dielectric coatings of the mirrors. It is shown that any two piezoelectrically scanned Fabry-Perot interferometers can be synchronized in tandem operation using simple optics and standard electronic driving and stabilization equipment. Applications of the tandem system to Brillouin scattering are given. The observation of Brillouin spectra of supported thin plastic films and of a clamped metal surface is reported. PMID- 20309317 TI - Measurement of submicron laser beam radii. AB - Three methods for direct measurement of the intensity distribution in laser beams focused by microscope optics to waists of submicron width are described and compared. They use scans of the beam waist with (1) a knife-edge, (2) a submicroscopic point fluorescent source, and (3) convolution scans generated by the photobleached pattern of the focused beam. An indirect photographic technique is also evaluated. The laser beam is found to propagate ideally down to a minimum size usually limited by the aberrations of the optics. PMID- 20309318 TI - Curved tube correction factors for indirect measurements with a radiation thermometer. AB - To measure surface temperature, a radiation guide in the form of a curved tube with a specular wall is used to couple thermal energy between a target surface and a radiometer. The relationship between the radiometer output and the target temperature depends on a correction factor, CF, which is a function of the tube temperature and another factor CFS. The term CFS, determined by the shape and reflectivity of the tube, is computed by a ray-trace technique. Calculations show how the factor CFS depends both on the ratio of tube length-to-diameter and length-to-bend radius. A particular gold-plated tube in conjunction with a radiometer having a narrowband filter at 7.9 microm is used to verify the relationship between surface temperature and radiometer output. Surface temperatures in the 0-100 degrees C range are measured for various fixed wall temperatures. There is good agreement between the measured and the calculated values. PMID- 20309319 TI - Whiteness: assessment of tint. AB - The tint of 431 white textile samples is visually assessed by 6 colorists. Tristimulus values based on measured spectral radiance factors of the samples are calculated for the CIE 1931 standard colorimetric observer and the CIE 1964 supplementary standard colorimetric observer. The parameters of colorimetric tint formulas are evaluated for both standard observers. PMID- 20309320 TI - Tapered fiber-optic sheet formation and its image-guiding properties. AB - Polymer fiber-optic sheets with tapered guides have been made by selective photopolymerization for use as image transformers. A new fabrication technique has been proposed, and good image-guiding properties have been achieved. It has been confirmed theoretically and experimentally that scatterers in cladding layers permit high resolution and surface cladding layers with large refractive index differences by polymer coating give high lighting efficiency. These tapered fiber-optic sheets used as an image reducer have resolutions of up to 6 lines/mm and lighting efficiency of ~4%. PMID- 20309321 TI - Optical Kerr effect in long fibers. AB - Optical Kerr modulation of >100% is demonstrated in long birefringent optical fibers using low laser powers of ~1 W. We have experimentally investigated the effects of group-velocity dispersion, thermal stability of polarization, and fiber birefringence. Use of fiber Kerr modulation as a fast optical shutter is studied, and it is concluded that resolution times shorter than 1 psec are possible in principle. PMID- 20309322 TI - Annual review of physical chemistry, vol. 31. Edited by B. S. Rabinovitch, j. M. Schurr, and h. L. Strauss. PMID- 20309323 TI - Energy transmission capacity of optical fibers determined by a temperature rise. AB - The temperature distribution in a step-index multimode optical fiber is calculated when light is launched into the core either as a cw or as a pulse train. It is shown that, after constant energy begins to flow in the core by a cw, the steady-state temperature depends strongly on the environment in which the fiber is placed. The energy transmission capacity of an optical fiber is defined as the input power which raises the temperature of the fiber to an acceptable level. When a plastic-coated fiber of 1-mm diam is placed in the air with free convection, the calculated capacity for a continuous input wave is ~820 W if the loss of the fiber is 10 dB/km. PMID- 20309324 TI - Patents patter. PMID- 20309325 TI - Measuring the complex frequency response of multimode optical fibers. AB - An improved frequency-sweeping method for measuring the complex frequency response (transfer function) H(omega) of multimode optical fibers is proposed. Measurement of the phase angle of H(omega) is difficult and has been performed infrequently and with poor accuracy. In the method proposed, this difficulty is overcome using a single-mode fiber as a reference for the phase angle of H(omega). The complex frequency responses of two multimode fibers measured with this new technique are shown and compared with pulse method results. PMID- 20309326 TI - Holographic measurement of refractive-index profile in the transition region of an optical fiber preform. AB - The refractive-index profile at the preform-fiber transition region was measured using holographic shearing interferometry. It involved the measurements of both the horizontal and vertical deflection functions. Analysis is also given on the ray trajectories in the transition region. It is shown that the vertical deflection of the rays has a significant influence on the measurement of the horizontal deflection function which is needed for reconstruction of the index profile. It is found from measurement results that there is a variation of the index profile as the preform is transformed into fiber. This is especially pronounced at the cladding region where boron is doped. PMID- 20309327 TI - Bistability and thresholding by a new photoconductor-twisted nematic liquid crystal device with optical feedback. AB - A new design for obtaining optical bistability in two dimensions is reported in this paper. This design uses optical feedback on a photoconductor-twisted nematic liquid crystal (PC-TNLC) device with a new structure. The PC-TNLC device is essentially a 2-D array of optically controlled light values. The device structure with a new arrangement of the photoconductor, the liquid crystal film, and a patterned transparent electrode gives better control over its input-output (I-O) response, which is important in obtaining bistable operation. A theoretical analysis is carried out to determine the conditions under which bistability occurs. A sharp transition from the OFF to ON state in the I-O response suggests that the thresholding operation on gray scale input images can be performed. Experimentally, an 8 x 8 PC-TNLC device with optical feedback was demonstrated to have bistable behavior. The ON:OFF ratio of 50:1 was obtained in the output. This device was also used to perform thresholding operation on a gray scale image with eight levels. The observed value of gamma for the thresholding operation was 8. Such a bistable device was shown to have potential applications in digital optical processing. PMID- 20309328 TI - Binarization effects in a correlator with noisy input data. AB - Correlations of binarized data and gray-scale data in the presence of additive noise are compared using two performance criteria (mean ratio and peak-to sidelobe ratio). General expressions are provided to evaluate these performance measures as a function of input data length, bandwidth, and signal-to-noise ratio. We find that binarized correlators outperform gray-scale correlators when the input SNR(i) exceeds a threshold level that depends on input bandwidth and sequence length. PMID- 20309329 TI - Implementation of an incoherent optical image restoration method: limitations related to optical subtraction. AB - Incoherent optical information processing is known to be far less sensitive to noise than coherent processing. However, it is restricted to real non-negative quantities. In cases like approximate deconvolution for image restoration, where positive and negative quantities are involved, the use of incoherent illumination is possible only at the expense of some additional sophistication needed to incorporate the negative parts; in particular, the restoration can be achieved by combining two incoherent convolutions and one subtraction. This paper describes an experiment of this type, with special emphasis on the practical implementation and on the difficulties related to the subtraction. Alignment and normalization of the two images to be subtracted are critical issues. If the subtraction is performed optically, the dynamic range of this operation is an additional problem. PMID- 20309330 TI - Optical information parallel processing: a technique. AB - A coherent optical information parallel processing technique using a multidiffraction grating is presented. We have shown that this parallel processing technique is capable of performing multichannel spatial filtering in the spatial frequency plane. The number of parallel processing channels is about 2N times the number of processing channels of the conventional coherent optical processor. However, in practice, the number of processing channels is limited by the number of multiplex gratings that can be synthesized and the available power of the light source. Extension of the monochromatic parallel processing system to polychromatic parallel processing is also presented. It can be shown that the number of processing channels of the polychromatic parallel processor is higher than the monochromatic parallel processor. Extension of this parallel processing concept to multisignal parallel processing is also discussed. However, the multisignal processing technique is not a real-time method because it requires an initial encoding step. Nevertheless, this disadvantage may be alleviated with ingenious design of the encoding system. We also assert that this parallel processing technique may be applied to white light parallel processing. PMID- 20309331 TI - First-order intensity and phase statistics of Gaussian speckle produced in the diffraction region. AB - General expressions for first-order statistics of Gaussian speckle produced in the diffraction region are derived for an arbitrary profile of the illuminating beam with a plane wave front. The statistical properties of the complex amplitude, the intensity, and the phase of speckles are studied under illumination of a Gaussian beam. The joint probability density function of the speckle field characterized by an equiprobability density ellipse is investigated in some detail with an intimate relation to the correlation coefficient between the real and imaginary parts of the complex speckle amplitude. This correlation coefficient is found to affect appreciably the statistics of speckles produced especially in the near-field diffraction region when a standard deviation of the random phase variation produced by a diffuse object under illumination is relatively small and the number of independent scatterers contributing to the formation of speckles is small. PMID- 20309332 TI - Vibration analysis by speckle techniques in real time. AB - Vibration analysis in quasi-real time is studied by recording the time-averaged speckle pattern in a bismuth silicon oxide crystal (Bi(12)SiO(20)). When the crystal is illuminated with a spherical wave, the spatially structured information from the time-averaged speckle pattern leads to fringes in the Fraunhofer plane. No storage device is required when the appropriate wavelength is chosen for writing and reading out the information. Experimental results will be presented together with a comparison of measurements obtained with a Doppler shift vibrometer. PMID- 20309333 TI - Reconstruction of a Fraunhofer hologram recorded near the focal plane of a transforming lens: experiment and results. AB - The holographic system for an optical memory is examined. A Fraunhofer hologram of an array object is recorded near the focal plane of a thick transforming lens. This hologram is read out with a spherical wave, and the intensity distribution in an image plane is theoretically calculated and experimentally measured. The concept of a traveling subaperture connected to a local recording of information in the hologram is verified. PMID- 20309334 TI - Measurement of nonlinear frequency chirp of Q-switched ruby laser. AB - The frequency chirp of a Q-switched ruby laser is investigated with two interference experiments: holography of a rotating object and measurement of time coherence. Nonlinearity of the frequency chirp markedly affects both interference experiments for large time differences between the two beams, which enable us to determine the nonlinear frequency chirp, that is, chirp rate and time. A hyperbolic tangent function provides a better approximation of the frequency chirp than the linear function generally used. In this experiment the chirp time was 1.0-1.5 times as long as the half-intensity width of the pulse. PMID- 20309335 TI - Calculation of the effective refractive-index step for the metal-cladded-ridge waveguide laser. AB - A newly developed stripe-geometry injection laser is presented with built-in passive waveguiding produced by an effective refractive-index step between active stripe and adjoining regions. In contrast with the similar CSP laser, however, confinement of the lasing mode is achieved by metal reflection instead of excess absorption loss outside the active stripe. A model for this type of injection laser is established, and a numerical analysis of the waveguiding mechanism is performed. As a result, design curves are obtained that directly determine the technological parameters required for diode preparation. PMID- 20309336 TI - Passive pulse shaping by spectral narrowing of picosecond pulses. AB - Synchronizing a picosecond laser pulse with a nanosecond one would be useful in laser fusion research. Amplitude modulation of a picosecond spectrum makes this possible; this passive technique has already been studied by C. Froehly and demonstrated by B. Colombeau. It is shown here that this kind of pulse shaper is usable on a power laser chain. Starting from a 40-psec pulse, several pulse shapes with durations up to 640- and 40-psec rise time have been obtained at different power levels. Efficiency and signal to noise ratio of the system have been studied. The diffraction-limited beam has been amplified in a power laser chain. PMID- 20309337 TI - Small fast large-aperture light modulator using attenuated total reflection. AB - An optical modulator is described which offers several advantages in terms of speed, aperture size, and ease of operation over other techniques for amplitude modulation of a collimated light beam. This simple device consists of a prism separated from a metallically reflecting surface by a small micron-size gap. Varying the gap thickness changes the intensity of the light reflected off the base of the prism. The prism acts as a coupler for the excitation of surface plasmons on the metallic surface. This paper explains the principle of operation and presents experimental results obtained on a simple realization of the device. PMID- 20309338 TI - Patents. AB - 3,989,890; 3,989,947; 3,994,435; 4,073,574; 4,150,320; 4,164,432; 4,165,913; 4,171,003; 4,165,917; 4,168,882; 4,175,391; 4,222,370; 4,206,494; 4,222,667; 4,225,240; 4,227,076; 4,225,236; 4,226,502; 4,227,769; 4,227,773; 4,228,437. PMID- 20309339 TI - General analysis of the projection speckle method. PMID- 20309340 TI - Bibliography on optical testing. PMID- 20309341 TI - Lidar evaluation of smoke and dust clouds. AB - Lidar provides the means to evaluate quantitatively the spatial and temporal variability of smoke and dust clouds as they are transported downwind from particulate sources. Quantitative evaluation of cloud optical and physical densities from cloud backscatter is complicated by effects from particle size, shape, and composition and by attenuation and multiple scattering for dense clouds. Examples are presented that review use of the lidar technique to provide useful evaluations of smoke and dust clouds. PMID- 20309342 TI - Simple inversion technique to obtain cloud droplet size parameters using solar aureole data. AB - A simple inversion technique in the single scattering regime has been developed to deduce cloud droplet size parameters by using the measurement of the radiance of near-forward scattered solar radiation as a function of angle. Compared with the numerical inversion technique that uses exact Mie scattering calculations, the new technique is much less time-consuming and hence should be usable in an on line real time analysis. To test the effectiveness of the new technique, we use the results of polydispersed cloud size distribution calculated by Deirmendjian to retrieve the model size parameters. The agreement is excellent. We also generalize the theory to include the broadband source. A typical experimental example is given. Its comparison with time-consuming Mie scattering inversion technique again shows excellent agreement. PMID- 20309343 TI - Characteristics of skylight at the zenith during twilight as indicators of atmospheric turbidity. 2: Intensity and color ratio. AB - This is the second of two papers based on an extensive series of measurements of the intensity and polarization of light from the zenith sky during periods of twilight made at an altitude of 3400 m on the island of Hawaii. Part 1 dealt with the skylight polarization; part 2 is on the measured intensity and quantities derived from the intensity. The principal results are that (1) the polarization and intensity of light from the zenith during twilight are sensitive indicators of the existence of turbid layers in the stratosphere and upper troposphere, and (2) at least at Mauna Loa primary scattering of the sunlight incident on the upper atmosphere during twilight is strongly dominant over secondary or multiple scattering at wavelengths beyond ~0.60microm, whereas this is much less true at shorter wavelengths. It is suggested that the development and general use of a simple twilight polarimeter would greatly facilitate determinations of turbidity in the upper layers of the atmosphere. PMID- 20309344 TI - Combined eye-atmosphere visibility model. AB - The effect of the earth's atmosphere on the visibility in the nadir direction, as determined by the human eye, is presented. The visibility characteristics can be obtained from the combined eye-atmosphere modulation transfer function. This function is applied to the calculation of visibility thresholds of an area of an albedo different from its surroundings. It is shown that the atmospheric effect of diffusing sharp boundaries between adjacent areas has a significant influence on the visibility threshold. A sensitivity study is carried out to investigate the effects of different atmospheric optical conditions on the visibility thresholds. This model emphasizes the use of a combined eye-atmosphere theory to predict visibility conditions from airplanes. PMID- 20309345 TI - General wavelength dependence of imaging through the atmosphere. AB - Atmospheric MTF formulations are restated to include contrast reduction by thermal backgrounds received by the imaging system. These backgrounds should be of significance for infrared imaging through the atmosphere. Absorption windows such as 2.0-2.4 and 3.1-4.1-microm wavelengths, which contain minimum atmospheric background, are suggested as usually permitting the best resolution for long range atmospheric imaging of apparently bright objects despite the fact that received object beam radiation may even peak in the 8-13-microm window. The 8-13 microm window is generally better for thermal imaging of objects whose temperatures are close to those of the atmosphere. PMID- 20309346 TI - Polarization imaging. AB - Although several attempts have been made in the past to use the partially polarized nature of optical fields in constructing images, the technique is not widely known or used. This paper reviews the principles of single-parameter polarization imaging and introduces the concept of multiparameter Stokes vector imaging. The Stokes vector image construction is discussed in the context of a recently introduced model of the human visual system perception space. It is shown that this perception space model allows one to take advantage of more of the information contained in the optical field to create an intelligible color display. The perception space model is also used to define a quantitative visual discrimination threshold applicable to multiparameter image construction and display. PMID- 20309347 TI - Optimum shape of a Kirkpatrick-Baez x-ray reflector supported at discrete points for on-axis performance. AB - Nested flat plates bent into the Kirkpatrick-Baez parabolic geometry and supported at discrete points are one means of obtaining large area grazing incidence x-ray optics with good angular resolution. A method for optimizing the on-axis resolution combining finite element and ray trace techniques with selective masking is presented. The optimally determined supported point location technique can lead to greatly reduced in situ labor costs. PMID- 20309348 TI - Fast camera for x rays: a novel concept. AB - In laser fusion and related fields the interaction between the laser and the target material is followed by the emission of x rays. The time history of these x rays is experimentally recorded by streak cameras. The currently used streak cameras have physical limitations for the temporal and spatial resolution limit. This paper presents a novel concept for a streak camera where these limitations are relaxed. In the camera described the photoelectron is moving in parallel electric and magnetic fields. The proposed design parameters use moderate fields and give time resolution limits of a few picoseconds and no spatial dispersion in one dimension. PMID- 20309349 TI - Directional pedestal-free laser Doppler velocimetry without frequency biasing. Part 1. AB - The spatial structure of the optical field on the detector of a laser Doppler velocimeter is examined. It is shown that for sufficiently small scatterers, the optical field is a traveling wave of shape determined by the detector optics alone. The direction of travel of the optical field reflects that of the scattering particle. Thus, the direction of motion of the particle is determined by temporal correlation of photocurrents from two spatially offset detector arrays. The arrays also eliminate the Doppler pedestal as shown by Ogiwara (1979). In this paper, the theory of the new method is described; experimental implementation will be described in a complementary paper. PMID- 20309350 TI - High frequency laser Doppler measurements using multiaxial-mode lasers. AB - Generally applicable laser Doppler anemometers have become commercially available and are now widely used for fluid flow studies. When used for high velocity measurements, e.g., in excess of 100 m/sec, laser Doppler anemometers usually comprise a high power argon-ion laser and a counter signal processor. A literature survey showed that most high speed LDA measurements have been carried out at Doppler frequencies much below the frequency capabilities of modern LDA frequency counters. This paper suggests that this might be due to the multiaxial mode output of cw lasers employed for high speed velocity measurements. The theory is discussed and experimental investigations are described that verify the theoretical results. These results suggest the use of single-mode lasers for high speed velocity measurements. The multiaxial-mode output of cw lasers is also claimed to be responsible for signal-to-noise ratio differences between LDA signals obtained with the blue and green lines of argon-ion lasers. The differences are only observed, however, when broadband detection systems are employed. Consideration is also given to the use of photodetectors for high frequency LDA systems. It is shown that photomultipliers that permit high anode currents are advantageous in laser Doppler anemometry; they are essential when measurements are made at high Doppler frequencies. Their use permits available high power lasers to be employed for LDA measurements and the high and basically noise-free gain of photomultipliers still to be used. PMID- 20309351 TI - Saturation of anomalous dispersion in cw HF lasers. AB - The high gain and narrow linewidth of HF chemical lasers lead to a large resonant component of the refractive index. Calculations indicate that this (unsaturated) anomalous dispersion is at least as large as the non-resonant Gladstone-Dale dispersion. Possible deleterious effects of anomalous dispersion are briefly reviewed. These effects in a high-power device are mitigated by multimode operation, which acts to saturate homogeneously the anomalous dispersion at intensities considerably lower than those required for power broadening of the inhomogeneous Doppler line shape over to a homogeneous line. PMID- 20309352 TI - Optimum mode size criterion for low-gain lasers. AB - The influence of the geometric relationship between laser pump and mode distributions on the performance of low-gain lasers has been analyzed. By considering cases in which the pump size is varied for a constant mode size and the mode size is varied for a constant pump size, a figure of merit has been defined through which laser performance can be optimized. The analysis shows that for any value of the pump radius R(o), the figure of merit is a maximum when omega, the 1/e radius of the Gaussian resonator mode, is approximately equal to R(o). PMID- 20309353 TI - Optogalvanic effect as a detector for intracavity atomic absorption in a cw dye laser. AB - It is demonstrated that the optogalvanic effect in a sodium hollow cathode discharge is a sensitive detector specific to the intracavity absorption of sodium atoms in a flame. In this feasibility study the variation of the optogalvanic signal vs the sodium concentration in the flame indicated a detection limit below 1 ng/ml. The sensitivity can be easily improved, and this technique is applicable to other atoms and Doppler-free intermodulation spectroscopic detection methods. PMID- 20309354 TI - Passively switched double-pass active mirror system. AB - Active mirror amplifiers have been demonstrated to be viable large aperture amplifiers for use in laser fusion systems. In addition to having a large storage efficiency (1.2-1.5%) at the highest pumping level and a thermal recovery time in the 15-30-min range, they are also scalable to large apertures and allow the propagation of circular polarization. An important additional property is that regardless of the angle of incidence, no birefringence occurs in active mirror amplifiers. Based upon a circular polarization scheme that allows passive switching, we have constructed and operated a double-passed active mirror system. For a 50-J input energy and a pulse width of 700 psec (Gaussian FWHM), we have measured a focusable output energy of approximately 230 J. Complementary single pass experiments resulted in an output energy of approximately 140 J, therefore, using the double-passed arrangement, we have increased the focusable output energy by ~64%. In this paper we describe the short-pulse (B-limited) and long pulse (damage-limited) staging of double-passed active mirror systems, discuss in detail the passive double-pass system, and describe its experimental verification. PMID- 20309355 TI - Dynamic pumping model for amplifier performance predictions. AB - Based upon time resolved spectroscopy of 13-mm xenon filled flashlamps, we have constructed a unique dynamic pumping model to predict the gain performance of active mirror amplifiers. The model, which includes the effects of spontaneous emission, concentration quenching, water quenching, and amplified spontaneous emission, uses only spectroscopy data from small glass samples as input. The use of the model in amplifier/system optimizations will be described. PMID- 20309356 TI - Reflective optics for irradiance redistribution of laser beams: design. AB - The output irradiance of a typical unstable resonator with circular symmetry has a central obscuration and is peaked near the obscuration. A method is presented for designing two-mirror optical systems to convert this beam into a beam of arbitrary obscuration ratio and more uniform irradiance. A method is also given for analyzing the alignment sensitivity of such a system. An example shows that useful irradiance redistributions can be achieved with alignment sensitivities comparable to ordinary Cassegrain systems. PMID- 20309357 TI - Mode properties of a strip confocal unstable resonator with saturable gain. AB - The asymptotic analysis technique for calculating the modes of unstable strip resonators is extended to include the effects of a saturable but otherwise uniform gain. Utilizing simultaneous forward and backward (in time) propagation and the Rigrod gain formula, an iterative algorithm is employed to find the intensities inside a resonator. In contrast with Fox-Li type iterations, this scheme converges rapidly and gives all the higher modes. Mode properties at critical Fresnel numbers are examined as a function of gain saturation, which is seen to reduce mode degeneracy. PMID- 20309358 TI - Modes of a laser resonator with a retroreflective mirror. AB - The self-consistent integral equation for the field distribution of the resonant modes in an inclined retroreflective grating resonator is solved in the limit of large Fresnel numbers. The transverse field distribution in the direction perpendicular to the grating grooves can be described in terms of Hermite Gaussian functions provided that lambda << d << w, where lambda is the wavelength, d is the grating spacing, and w is the beam spot size. PMID- 20309359 TI - Correlator based on an integrated optical spatial light modulator. AB - The fabrication and characterization of a 17.5-M bit/sec integrated optical correlator are described. The correlator makes use of a novel programmable electrooptic spatial light modulator in conjunction with a digitally modulated surface acoustic wave. PMID- 20309360 TI - Integrated Fresnel lens on thermally oxidized silicon substrate. AB - Thin film Fresnel lenses have been achieved on SiO(2)/Si substrates covered with a waveguide layer of Si(3)N(4) grown by low pressure chemical vapor deposition (LPCVD). The phase shift between the different zones is induced by a SiO(2) top layer chemically etched. The use of this additional layer having a smaller refractive index than the waveguide results in a saturation of the lens characteristics vs the thickness of the SiO(2) layer; this feature associated with the good reproducibility of the LPCVD technology allows good control of the lens characteristics. PMID- 20309361 TI - Interrelationship between water absorption loss and dispersion in multimode fiber. AB - Similarities between fiber bandwidth spectra and loss spectra are found to occur. Wavelength-dependent far-field radiation patterns were used to deduce that high OH ion concentrations, near the center of the core, caused differential attenuation of low-order modes. This resulted in bandwidth peaks at the same wavelengths where water absorption loss peaked. PMID- 20309362 TI - Low reflectance terminations and connections for duplex fiber-optic telecommunication links. AB - The signal-to-noise ratio of full duplex fiber-optic telecommunication links using a single fiber with directional couplers is shown to be extremely sensitive to reflections from fiber end terminations and fiber-to-fiber connections. This paper will examine a series of experimental measurements made to determine the reflectance coefficients of several different end terminations and types of connection. PMID- 20309363 TI - Optical fiber profiles using the refracted near-field technique: a comparison with other methods. AB - Multimode fiber profiles by the refracted near-field method (RNF) agree to within +/-0.5% with profiles obtained by the highly accurate interferometric slab technique in regions of adequate resolution of the latter. Nineteen multimode fiber profiles by the RNF and transverse interferometric methods differ in Delta and alpha on the average by 4% and 3%, respectively. The precision of a refractive-index determination by the RNF technique is 4 x 10(-5). A rapid method of calibrating the profiles by measuring the liquid temperature is presented, and the effect of foreign matter on the fiber face is discussed. PMID- 20309364 TI - Modal noise in optical fibers: open and closed speckle pattern regimes. AB - Modal noise generation in multimode optical fiber is identified as occurring in two statistically differing regimes, that in which there is independence of the speckles (open regime) and that in which the speckles have an interdependency related to the constancy of the total light power in the core modes (closed regime). We derive statistical expressions for modal noise generation in the closed regime and verify them with experiment. PMID- 20309365 TI - Characteristics of holographic scanners utilizing a concave auxiliary reflector. AB - The characteristics of 2-D holographic scanners utilizing a concave auxiliary reflector are analyzed. The total resolution capability of the scanner is discussed in detail for the scanner operated at both finite and infinite conjugations, and the factors limiting resolution are indicated. The resolution considerations lead to a near-optimal design procedure which is used in design examples for typical applications in the visible, millimeter, and ultrasonic wavelength regions. PMID- 20309366 TI - Endoscopic hologram interferometry using fiber optics. AB - Basic and practical problems on the formation of fringes in endoscopic hologram interferometry using fiber optics have been studied in connection with medical diagnosis of living body cavities, nondestructive testing of inner parts of machines, etc. It is pointed out that fiber bundles instead of single fibers can be used to transmit high power laser light for object illumination to prevent the light path break induced by the high power density of concentrated laser light. The effects of extended source illumination by the fiber bundle, image transmission through the ordered fiber bundle, and fiber bundle movement on the fringe visibility were investigated. PMID- 20309367 TI - Spatial resolution for two-beam spectroscopy: a new mechanism. AB - With the help of interference effects, two-beam and multiple-beam spectroscopy detect in the pairs of beams (bundles of rays selected by the optical system) phase correlations due to certain fluctuations in optically thin distributions of incoherent light sources. Originally spatial resolution along the line of sight was expected for multiple-beam spectroscopy because of the limited region of intersection for pairs of beams. Here more general analysis shows another mechanism of spatial resolution allowing use of broader overlapping beams. Thus a simpler two-beam spectroscopy configuration (to be discussed in more detail elsewhere) capable of making more efficient use of emitted light proves to offer the same localized measurement of spatially harmonic fluctuations in the appropriate light source distributions. PMID- 20309368 TI - Heterodyne frequency measurements on the 11.6-microm band of OCS: new frequency/wavelength calibration tables for 11.6- and 5.8-microm OCS bands. AB - Heterodyne difference frequency measurements between a (13)CO(2) laser and a diode laser tuned (and in most cases locked) to the peaks of OCS absorption lines have been used to improve frequency calibration tables in the 860-cm(-1) region by factors of 20-50. Measurements have been made on the vibrational transitions 10(0)0-00(0)0, 11(1)0-01(1)0, and 20(0)0-10(0)0 for OCS. The measurements on the 10(0)0-00(0)0 and 20(0)0-10(0)0 transitions are also used to provide frequency calibration tables for the 20(0)0-00(0)0 band of OCS near 1700 cm(-1). PMID- 20309369 TI - Angular distribution of coherent Raman emission in degenerate four-wave mixing with pumping by a single diffraction coupled laser beam: configurations for high spatial resolution. AB - This paper contains a discussion of the relation between the angular distributions of the coherently emitted radiation and the angular distribution of the incident beams in a degenerate four-wave mixing experiment, when two of the input beams are derived from the same laser source. The objective of the discussion is to obtain beam configurations that permit the use of such spectroscopic techniques when good spatial resolution is required so that the conventional collinear phase matching geometry is inappropriate. Two different configurations are indeed obtained and experimentally demonstrated that have, in the worst direction (longitudinal), spatial resolution of the order of 1 mm, with beam apertures comparable with those used in the standard collinear experiments and without the complicating requirement of two distinct pump beams. PMID- 20309370 TI - Temperature dependence of the self-broadening coefficients for the fundamental band of carbon monoxide. AB - The exponent eta for the temperature dependence of the self-broadening coefficient of carbon monoxide has been measured directly using a tunable diode laser spectrometer. For lines of (12)C(16)O between P(25) and P(31), the exponent has a value of 0.66 +/- 0.05. For the P(13) and P(16) lines of (13)C(16)O, the exponent appears to be the same. These results show that the value of eta is less than the generally accepted value of 0.75 for temperatures between ambient and 180 degrees C. PMID- 20309371 TI - Optical water quality model of Lake Ontario. 1: Determination of the optical cross sections of organic and inorganic particulates in Lake Ontario. AB - A five-component optical model of Lake Ontario is discussed in terms of unique organics (as represented by chlorophyll a), unique inorganics (as represented by total suspended minerals), unique nonliving organics, and unique dissolved organics. Direct measurements of the irradiance attenuation coefficient K(0), the diffuse reflectance R(0), and the total atttenuation coefficient c are used in conjunction with simulated solutions of the radiative transfer equations to determine the inherent optical properties of the water masses. Multiple regressions between these inherent optical properties and directly measured water quality data are then performed to determine the absorption, scattering, and backscattering cross sections of the organic and inorganic components. PMID- 20309373 TI - Fabry-Perot filters used for optical preprocessing. AB - A Fabry-Perot etalon placed in the object plane of a coherent optical processing system can be used as a variable bandpass preprocessing filter. Use of this filter leads to improved correlation signals in a matched spatial filter system. Experimental results are shown and compared with results obtained by two other preprocessing methods. PMID- 20309372 TI - Optical water quality model of Lake Ontario. 2: Determination of chlorophyll a and suspended mineral concentrations of natural waters from submersible and low altitude optical sensors. AB - Spectrooptical and water quality data collected from a 1979 coordinated in situ and airborne study of western Lake Ontario are used to devise a five-component model from which subsurface chlorophyll a and suspended solids concentrations may be determined from submersible optical sensors capable of measuring spectral irradiance reflectance just beneath the free-surface layer. A water-air interface model, which incorporates the effects of surface reflection, is also presented in an attempt to extend such water quality estimations to low altitude remote sensors. Special emphasis is given to the spectral wavelength bands of the Coastal Zone Color Scanner aboard Nimbus-7. PMID- 20309374 TI - Fluorescence standard reference material: quinine sulfate dihydrate. PMID- 20309375 TI - Image contrast reversal with a photorefractive recording medium. AB - Images with partial and complete contrast reversal have been retrieved from a single image recorded in a lithium niobate crystal. The input image, a grey tone transparency, is modulated with the help of two diffracted orders of a Ronchi ruling. The same two orders are used to read the crystal. The relative amplitude of these orders is altered with the help of a linear polarizer, and this produces variable tones in the output image. Partially coherent light can be used at both the writing and the reading stages. PMID- 20309376 TI - Defect-type discriminating optical system. AB - Novel coherent optical defect detecting methods, which can distinguish between opaque defects and transparent defects, are proposed. One of these novel methods makes use of a holographylike polarity reference signal and is suited to automatic detection systems. The other employs two independent light sources, and suitable for visual detection systems. Realizing these novel methods using omnidirectional spatial filters, simple but effective periodic pattern defect detecting systems are formed, which can be easily accommodated with defect touching-up stages. PMID- 20309377 TI - A perfect storm in interventional pain management: regulated, but unbalanced. AB - Interventional pain management now stands at the crossroads at what is described as "the perfect storm." The confluence of several factors has led to devastating results for interventional pain management. This article seeks to provide a perspective to various issues producing conditions conducive to creating a "perfect storm" such as use and abuse of interventional pain management techniques, and in the same context, use and abuse of various non-interventional techniques. The rapid increase in opioid drug prescribing, costs to health care, large increases in death rates, and random and rampant drug testing, can also lead to increases in health care utilization. Other important aspects that are seldom discussed include medico-legal and ethical perspectives of individual and professional societal opinions and the interpretation of diagnostic accuracy of controlled diagnostic blocks. The aim of this article is to discuss the impact of several factors on interventional pain management and overuse, abuse, waste, and fraud; inappropriate application without evidence-based literature support (sometimes leading to selective use or non-use of randomized or observational studies for proving biased viewpoints - post priori rather than a priori), and issues related to multiple professional societies having their own agendas to push rather than promulgating the science of interventional pain management. This perspective is based on a review of articles published in this issue of Pain Physician, information in the public domain, and other relevant articles. Based on the results of this review, various issues of relevance to modern interventional pain management are discussed and the viewpoints of several experts debated. In conclusion, supporters of interventional pain management disagree on multiple aspects for various reasons while detractors claim that interventional pain management should not exist as a speciality. Issues to be addressed include appropriate use of evidence-based medicine (EBM), overuse, overutilization, and abuse. PMID- 20309378 TI - A systematic review on the effectiveness of the Nucleoplasty procedure for discogenic pain. AB - BACKGROUND: Nucleoplasty is a minimally invasive procedure for treating pain caused by symptomatic disc herniation that is refractory to conservative therapy. Observational studies have reported differing outcomes for this procedure and thus its effectiveness is yet to be determined. STUDY DESIGN: A systematic review of the efficacy of the nucleoplasty procedure. OBJECTIVES: To assess the clinical efficacy of the nucleoplasty procedure for treating back pain from symptomatic, contained disc herniation and to evaluate the methodological quality of the included studies. METHODS: The relevant literature for nucleoplasty was identified through a search of the following databases: Pubmed, Ovid Medline, and the Cochrane library, and by a review of the bibliographies of the included studies. A review of the literature of the effectiveness of the nucleoplasty procedure for managing discogenic pain was performed according to the criteria for observational studies using a "Quality Index" scale to determine the methodological quality of the literature. The level of evidence was classified as Level I, II, or III based on the quality of evidence developed by the United States Preventive Services Task Force (USPSTF) for therapeutic interventions. Recommendations were based on the criteria developed by Guyatt et al. OUTCOME MEASURES: The main outcome measures evaluated were the percentage of pain relief based on visual analogue scale (VAS) or numeric rating scale (NRS), percentage of patients with more than 50% reduction in pain, percentage of patients meeting one or more success criteria after nucleoplasty, and improvement in patient function. Secondary measures noted were reports of complications and the Quality Index scores of each study that was evaluated. RESULTS: The quality of evidence for improvement in pain or function after a nucleoplasty procedure is Level II-3. The recommendation is 1C/strong for the nucleoplasty procedure based on the quality of evidence available. The median Quality Index score was 16 (range 12 - 19), indicating adequate methodological quality of the available literature. None of the studies reported major complications related to nucleoplasty. CONCLUSIONS: Observational studies suggest that nucleoplasty is a potentially effective minimally invasive treatment for patients with symptomatic disc herniations who are refractory to conservative therapy. The recommendation is a level 1C, strongly supporting the therapeutic efficacy of this procedure. However, prospective randomized controlled trials with higher quality of evidence are necessary to confirm efficacy and risks, and to determine ideal patient selection for this procedure. PMID- 20309379 TI - Making sense of the accuracy of diagnostic lumbar facet joint nerve blocks: an assessment of the implications of 50% relief, 80% relief, single block, or controlled diagnostic blocks. AB - BACKGROUND: The presence of lumbar facet joint pain has been overwhelmingly supported and the accuracy of controlled diagnostic blocks has been demonstrated in multiple studies and confirmed in systematic reviews. However, controversy surrounds the following related issues: placebo control, the amount of relief (50% versus 80%), single block versus double block, and placebo or comparative control. STUDY DESIGN: An observational report of an outcome study to establish the diagnostic accuracy of controlled lumbar facet joint nerve blocks. SETTING: An interventional pain management practice setting in the United States. OBJECTIVE: To determine the accuracy of controlled diagnostic blocks in managing lumbar facet joint pain at the end of 2 years, with 2 different criteria (50% or 80% relief) and single block versus double block. METHODS: A previous study of 152 patients showed an 89.5% of sustained diagnosis of lumbar facet joint pain at the end of a 2-year follow-up period when the diagnosis was made with double blocks and at least 80% relief. The present evaluation includes comparison of the above results with a study of 110 patients undergoing lumbar facet joint nerve blocks with positive criteria of at least 50% relief and follow-up of 2 years. The inclusion criteria in both studies was based on a positive response to diagnostic controlled comparative local anesthetic lumbar facet joint blocks, with either 50% or 80% relief and the ability to perform previously painful movements. The treatment in both groups included therapeutic lumbar facet joint interventions either with facet joint nerve blocks or radiofrequency neurotomy. OUTCOME MEASURES: The sustained diagnosis of lumbar facet joint pain at the end of one year and 2 years based on pain relief and functional status improvement. RESULTS: At the end of one year, the diagnosis was confirmed in 75% of the group with 50% relief, whereas it was 93% in the group with 80% relief. At the end of the 2-year follow-up, the diagnosis of lumbar facet joint pain was sustained in 51% of the patients in the group with 50% relief, whereas it was sustained in 89.5% of the patients with 80% relief. The results differed between 50% relief and 80% relief with prevalence of 61% facet joint pain with dual blocks with 50% relief, and 31% with dual blocks with 80% relief; whereas with only a single block, the prevalence was 73% with 50% relief and 53% in the 80% relief group. LIMITATIONS: The study is limited by its observational nature. CONCLUSION: Controlled diagnostic lumbar facet joint nerve blocks are valid utilizing the criteria of 80% pain relief and the ability to perform previously painful movements, with a sustained diagnosis of lumbar facet joint pain in at least 89.5% of the patients at the end of a 2-year follow-up. In contrast, the diagnosis was sustained in 51% of the patients with 50% relief at the end of 2 years. Thus, inappropriate diagnostic criteria will increase the prevalence of facet joint pain substantially, leading to inappropriate and unnecessary treatment. PMID- 20309380 TI - A medical-legal review regarding the standard of care for epidural injections, with particular reference to a closed case. AB - Interventional pain management is an evolving field, with a primary focus on the safety of the patient. One major source of risk to patients is intraarterial or intraneural injections. Interventional pain physicians have considerable interest in identifying techniques which avoid these complications. A recent article has reviewed complications associated with interventional procedures and concluded that the complications were due to deviation from a specific prescribed protocol. One of the cases reviewed went to jury trial and the record of that case is in the public domain. Two of the authors of the recent review were expert witnesses in the trial. They provided conflicting testimony as to alleged violations of the standard of care. Their criticisms also differed from a third criticism contained in the article as well as the protocol being advocated in the article, thus contravening the claim that there is one prescribed protocol which must be followed. The definition of standard of care varies amongst jurisdictions, but is generally defined as either that care which a reasonably well-trained physician in that specialty would provide under similar circumstances or as what would constitute reasonable medical care under the circumstances presented. Analysis of the case which went to trial indicates that there is not one prescribed protocol which must be followed; the definition of standard of care is broader than that. Interventional pain management is an evolving field and the standard of care is broadly defined. PMID- 20309381 TI - Intrathecal catheter-syringe adaptor for short-term intrathecal analgesia with an externalized pump: a case report. AB - BACKGROUND: In most patients, cancer pain is effectively treated with conservative medical management consisting of oral and/or transdermal analgesics. Cancer patients tend to fail conservative medical management near the end of their life expectancy, thus requiring alternative routes of analgesia such as intravenous, epidural, or intrathecal. The intrathecal route provides the most effective analgesia due to the close proximity of the opioid receptors in the spinal cord. Though there are many techniques that exist for intrathecal drug delivery, complications can limit effectiveness such as infection, bleeding, cerebrospinal fluid (CSF) leaks, post-dural puncture headaches (PDPH), pump and/or catheter malfunctions, or limitations of technical expertise. Therefore, an important goal in palliative cancer pain therapy is to use equipment that is going to have the fewest number of complications and will be the most familiar to the health care providers. We describe the combination of the Medtronic Indura 1P catheter, which has the least catheter-related complications and can be used with any external drug infusion pump. These are regular infusion pumps that the health care workers are familiar with so they can provide excellent and efficient service to the patient. METHODS: In an operating room, the intrathecal catheter was placed using sterile technique under fluoroscopic guidance. The epidural space was identified with loss of resistance technique. Then the introducer needle (supplied in the Indura 1P catheter kit) was advanced until free-flowing CSF was obtained. The spinal catheter was advanced into the intrathecal space through the introducer needle to lumbar 2-3 level. The catheter was tunneled subcutaneously 10 cm lateral to the catheter exit site. A syringe filling device was inserted into the catheter opening and was secured with silk suture. A luer lock syringe was attached to the syringe filling device and CSF was aspirated. The syringe filling device was capped and later attached to an external drug infusion pump. RESULTS: We report the successful use of the Medtronic Indura 1P, one piece intrathecal catheter, connected to the external drug pump for a 3 week period in a patient with metastatic cervical cancer for palliative pain control. LIMITATIONS: Case report only. CONCLUSION: This technique is simple to perform by pain specialists. The catheter modification allows the use of the Medtronic intrathecal catheter with standard external drug infusion pumps. This facilitates the patient's care in the hospice setting. PMID- 20309382 TI - Intracranial neurostimulation for pain control: a review. AB - Intracranial neurostimulation for pain relief is most frequently delivered by stimulating the motor cortex, the sensory thalamus, or the periaqueductal and periventricular gray matter. The stimulation of these sites through MCS (motor cortex stimulation) and DBS (deep brain stimulation) has proven effective for treating a number of neuropathic and nociceptive pain states that are not responsive or amenable to other therapies or types of neurostimulation. Prospective randomized clinical trials to confirm the efficacy of these intracranial therapies have not been published. Intracranial neurostimulation is somewhat different than other forms of neurostimulation in that its current primary application is for the treatment of medically intractable movement disorders. However, the increasing use of intracranial neurostimulation for the treatment of chronic pain, especially for pain not responsive to other neuromodulation techniques, reflects the efficacy and relative safety of these intracranial procedures. First employed in 1954, intracranial neurostimulation represents one of the earliest uses of neurostimulation to treat chronic pain that is refractory to medical therapy. Currently, 2 kinds of intracranial neurostimulation are commonly used to control pain: motor cortex stimulation and deep brain stimulation. MCS has shown particular promise in the treatment of trigeminal neuropathic pain and central pain syndromes such as thalamic pain syndrome. DBS may be employed for a number of nociceptive and neuropathic pain states, including cluster headaches, chronic low back pain, failed back surgery syndrome, peripheral neuropathic pain, facial deafferentation pain, and pain that is secondary to brachial plexus avulsion. The unique lack of stimulation-induced perceptual experience with MCS makes MCS uniquely suited for blinded studies of its effectiveness. This article will review the scientific rationale, indications, surgical techniques, and outcomes of intracranial neuromodulation procedures for the treatment of chronic pain. PMID- 20309383 TI - Importance of urine drug testing in the treatment of chronic noncancer pain: implications of recent medicare policy changes in kentucky. AB - BACKGROUND: Urine drug testing has become a widely used tool in American society for deterring illicit drug use. In the practice of medicine, urine drug testing is commonly used to help diagnose substance misuse, abuse, or addiction. OBJECTIVE: This narrative review provides an informed perspective on the importance of urine drug testing in the medical treatment of chronic noncancer pain. The history and current uses of urine drug tests in the United States are reviewed, the prevalence and nature of prescription drug misuse is described as is related to chronic noncancer pain, and implications and considerations for practitioners are presented related to the noncancer pain diagnosis and treatment. DISCUSSION: Practitioners are confronted with the ethical and legal dilemma of being called to adequately treat chronic pain in a culture with a high prevalence of prescription drug abuse. Yet the symptoms of drug abuse are nonspecific and therefore of limited value to the practitioner in determining patient compliance to drug treatment regimens. In contrast, urine drug testing has a reliable history, both in and out of medicine, as an independent sign of drug misuse. This sign can be used to aid in the diagnosis and treatment of drug misuse and underlying addictions to improve patient outcomes. CONCLUSION: Regular urine drug testing should be a part of acute and chronic pain management whether or not the patient has any signs or symptoms of drug misuse. PMID- 20309384 TI - Urine drug testing in the treatment of chronic noncancer pain in a Kentucky private neuroscience practice: the potential effect of Medicare benefit changes in Kentucky. AB - BACKGROUND: Because the symptoms of drug misuse are nonspecific and difficult to detect, pain physicians have relied heavily on the results of urine drug tests to diagnose and treat chronic noncancer pain in patients who are prescribed controlled substances. However, changes in Medicare local carrier determinations for Medicare Part B providers in Connecticut, Indiana, Kentucky, and New York went into effect on July 1, 2009, whereby qualitative drug screening was no longer recognized as medically reasonable and necessary in the treatment of patients with chronic noncancer pain unless the patient presents with suspected drug overdose. STUDY DESIGN: A retrospective review of urine drug testing services. OBJECTIVE: To determine the extent of urine drug testing in patients with chronic noncancer pain in a large, Kentucky neuroscience practice offering pain management services combined with neurologic and neurosurgical services to better understand the potential effects of recent changes to Medicare benefits. METHODS: An audit of services provided during 2007 was conducted using computer software. OUTCOME MEASURES: Outcome measures included the number of practice services, number of urine drug tests by payor, and the number of noncompliant patients by payor who self-released from care. RESULTS: Urine drug tests represented approximately 18.2% of professional medical services rendered in 2007 to patients with a diagnosis of chronic noncancer pain. Of these, UDTs represented approximately 22.2% of services provided to Medicare patients and 24.6% of services provided to Medicaid patients. In 2007, 2,081 patients with noncompliant UDTs self released from the practice against medical advice. Of these, 23.1% were enrolled in Medicare and 47.5% were enrolled in Medicaid. Approximately 40% of patients were referred to the CARE Clinic on the basis of noncompliance as indicated by UDT and/or behavioral health issues. Of these, approximately 50% remained in treatment. Urine drug tests were also instrumental in revealing that 19.6% of patients showed signs of drug abuse or addiction. Of these patients, approximately 60% were government insured. LIMITATIONS: Not a prospective, double-blinded study. We approximated the proportion of patients potentially affected by drug abuse or addiction as the percentage of patients self releasing from medical care. CONCLUSION: In 2007, UDTs were used as an effective tool in adherence monitoring in a private neuroscience practice in Kentucky that offers pain management services combined with neurologic and neurosurgical services. UDTs were instrumental in referring 40% of patients for evaluation and treatment by behavioral health and addiction medicine specialists. UDTs were also instrumental in discovering signs of drug abuse or addiction in 19.6% of patients. Of these patients, approximately 60% were government insured. Should the objective and reliable sign offered by UDTs be eliminated from the physician's toolbox, the physician's ability to accurately diagnose and treat these patients could be impaired. PMID- 20309385 TI - Neurostimulation article clarification. PMID- 20309386 TI - Herpes zoster: are selective nerve root injections the treatment or the cause? PMID- 20309387 TI - In response to Herpes zoster: are selective nerve root injections the treatment or the cause? PMID- 20309388 TI - Interventional pain management at crossroads: the perfect storm brewing for a new decade of challenges. AB - The health care industry in general and care of chronic pain in particular are described as recession-proof. However, a perfect storm with a confluence of many factors and events -none of which alone is particularly devastating - is brewing and may create a catastrophic force, even in a small specialty such as interventional pain management. Multiple challenges related to interventional pain management in the current decade will include individual and group physicians, office practices, ambulatory surgery centers (ASCs), and hospital outpatient departments (HOPD). Rising health care costs are discussed on a daily basis in the United States. The critics have claimed that health outcomes are the same as or worse than those in other countries, but others have presented the evidence that the United States has the best health care system. All agree it is essential to reduce costs. Numerous factors contribute to increasing health care costs. They include administrative costs, waste, abuse, and fraud. It has been claimed the U.S. health care system wastes up to $800 billion a year. Of this, fraud accounts for approximately $200 billion a year, involving fraudulent Medicare claims, kickbacks for referrals for unnecessary services, and other scams. Administrative inefficiency and redundant paperwork accounts for 18% of health care waste, whereas medical mistakes account for $50 billion to $100 billion in unnecessary spending each year, or 11% of the total. Further, American physicians spend nearly 8 hours per week on paperwork and employ 1.66 clerical workers per doctor, more than any other country. It has been illustrated that it takes $60,000 to $88,000 per physician per year, equal to one-third of a family practitioner's gross income, and $23 to $31 billion each year in total to interact with health insurance plans. The studies have illustrated that an average physician spends $68,274 per year communicating with insurance companies and performing other non-medical functions. For an office-based practice, the overall total in the United States is $38.7 billion, or $85,276 per physician. In the United States there are 2 types of physician payment systems: private health care and Medicare. Medicare has moved away from the Medicare Economic Index (MEI) and introduced the sustainable growth rate (SGR) formula which has led to cuts in physician payments on a yearly basis. In 2010 and beyond into the new decade, interventional pain management will see significant changes in how we practice medicine. There is focus on avoiding waste, abuse, fraud, and also cutting costs. Evidence-based medicine (EBM) and comparative effectiveness research (CER) have been introduced as cost-cutting and rationing measures, however, with biased approaches. This manuscript will analyze various issues related to interventional pain management with a critical analysis of physician payments, office facility payments, and ASC payments by various payor groups. PMID- 20309389 TI - Protocol for evaluation of the comparative effectiveness of percutaneous adhesiolysis and caudal epidural steroid injections in low back and/or lower extremity pain without post surgery syndrome or spinal stenosis. AB - BACKGROUND: Treatment of chronic low back pain with or without lower extremity pain continues to be a challenge. Epidural steroids are commonly utilized in patients after the failure of conservative treatment. The results of epidural steroid injections have been variable based on the pathophysiology, the route of administration, injected drugs, and utilization of fluoroscopy. In patients resistant to fluoroscopically directed epidural injections, percutaneous epidural adhesiolysis and percutaneous targeted delivery of injections with or without adhesiolysis has been recommended. Percutaneous adhesiolysis has been studied in chronic pain syndromes related to post laminectomy syndrome and spinal stenosis with encouraging results. There is a paucity of literature regarding the effectiveness of the targeted delivery of medications with or without epidural adhesiolysis in patients recalcitrant to epidural steroid injections without a history of surgery and spinal stenosis. STUDY DESIGN: A randomized, equivalence trial of percutaneous lumbar adhesiolysis and caudal epidural steroid injections in patients with low back and/or lower extremity pain without post surgery syndrome or spinal stenosis. SETTING: An interventional pain management practice setting in the United States. OBJECTIVE: The study is designed to evaluate the effectiveness of percutaneous epidural adhesiolysis in managing chronic low back and/or lower extremity pain in patients without post lumbar surgery syndrome or spinal stenosis and compare it with fluoroscopically directed caudal epidural steroid injections METHODS: The study design includes 120 patients randomly assigned into 2 groups. Group I (60 patients), the control group, will receive caudal epidural injections with catheterization up to S3 with local anesthetic, steroids, and 0.9% sodium chloride solution; Group II (60 patients), the intervention group, will receive percutaneous adhesiolysis with target delivery of lidocaine, 10% hypertonic sodium chloride solution, and non-participate betamethasone. Randomization will be performed by computer-generated random allocation sequence by simple randomization. OUTCOME MEASURES: Multiple outcome measures will be utilized including numeric rating scale (NRS), the Oswestry Disability Index 2.0 (ODI), employment status, and opioid intake with assessment at 3, 6, 12, 18 and 24 months post treatment. Significant pain relief is considered as 50% or more, whereas significant improvement in the disability score is defined as a reduction of 40% or more. RESULTS: The results will be analyzed to show significant relief as well as improvement in functional status. LIMITATIONS: This study is limited by potentially inadequate double blinding and the lack of a placebo group. PMID- 20309390 TI - Olfactory discrimination training up-regulates and reorganizes expression of microRNAs in adult mouse hippocampus. AB - Adult male mice (strain C57Bl/6J) were trained to execute nose-poke responses for water reinforcement; then they were randomly assigned to either of two groups: olfactory discrimination training (exposed to two odours with reward contingent upon correctly responding to one odour) or pseudo-training (exposed to two odours with reward not contingent upon response). These were run in yoked fashion and killed when the discrimination-trained mouse reached a learning criterion of 70% correct responses in 20 trials, occurring after three sessions (a total of approximately 40 min of training). The hippocampus was dissected bilaterally from each mouse (N = 7 in each group) and profiling of 585 miRNAs (microRNAs) was carried out using multiplex RT-PCR (reverse transcription-PCR) plates. A significant global up-regulation of miRNA expression was observed in the discrimination training versus pseudo-training comparison; when tested individually, 29 miRNAs achieved significance at P = 0.05. miR-10a showed a 2.7 fold increase with training, and is predicted to target several learning-related mRNAs including BDNF (brain-derived neurotrophic factor), CAMK2b (calcium/calmodulin-dependent protein kinase IIbeta), CREB1 (cAMP-response element-binding protein 1) and ELAVL2 [ELAV (embryonic lethal, abnormal vision, Drosophila)-like; Hu B]. Analysis of miRNA pairwise correlations revealed the existence of several miRNA co-expression modules that were specific to the training group. These in vivo results indicate that significant, dynamic and co ordinated changes in miRNA expression accompany early stages of learning. PMID- 20309391 TI - Serial observations and mutational analysis of an adoptee with family history of hypertrophic cardiomyopathy. AB - Hypertrophic cardiomyopathy (HCM) is an inherited cardiac disease with an autosomal dominant mode of transmission. Comprehensive genetic screening of several genes frequently found mutated in HCM is recommended for first-degree relatives of HCM patients. Genetic testing provides the means to identify those at risk of developing HCM and to institute measures to prevent sudden cardiac death (SCD). Here, we present an adoptee whose natural mother and maternal relatives were known be afflicted with HCM and SCD. The proband was followed closely from age 6 to 17 years, revealing a natural history of the progression of clinical findings associated with HCM. Genetic testing of the proband and her natural mother, who is affected by HCM, revealed that they were heterozygous for both the R719Q and T1513S variants in the cardiac beta-myosin heavy chain (MYH7) gene. The proband's ominous family history indicates that the combination of the R719Q and T1513S variants in cis may be a "malignant" variant that imparts a poor prognosis in terms of the disease progression and SCD risk. PMID- 20309392 TI - Severe outcome of pharyngeal-cervical-brachial pure motor axonal neuropathy. AB - We present two further cases of the pharyngeal-cervical-brachial (PCB) form of GBS, with unfavourable outcome, showing dramatic dissociation between upper and lower body Symptoms. Both patients showed rapidly progressive motor denervation with disappearance of Compound Muscle Action Potentials (CMAPs) in upper limbs muscles. Sensory Nerve Action Potentials (SNAPs) were instead normal. Normal reflexes, F waves and action potentials were elicited in lower limbs. Despite i.v. Immunoglobulin treatment no recovery was observed and both patients died within a year from onset of symptoms. PMID- 20309393 TI - Theoretical modeling for hepatic microwave ablation. AB - Thermal tissue ablation is an interventional procedure increasingly being used for treatment of diverse medical conditions. Microwave ablation is emerging as an attractive modality for thermal therapy of large soft tissue targets in short periods of time, making it particularly suitable for ablation of hepatic and other tumors. Theoretical models of the ablation process are a powerful tool for predicting the temperature profile in tissue and resultant tissue damage created by ablation devices. These models play an important role in the design and optimization of devices for microwave tissue ablation. Furthermore, they are a useful tool for exploring and planning treatment delivery strategies. This review describes the status of theoretical models developed for microwave tissue ablation. It also reviews current challenges, research trends and progress towards development of accurate models for high temperature microwave tissue ablation. PMID- 20309394 TI - Autonomic dysfunction presenting as postural orthostatic tachycardia syndrome in patients with multiple sclerosis. AB - BACKGROUND: Autonomic dysfunction is common in patients suffering from multiple sclerosis (MS) and orthostatic dizziness occurs in almost 50% of these patients. However, there have been no reports on postural orthostatic tachycardia syndrome (POTS) in patients suffering from MS. METHODS: The patients were included for analysis in this study if they had POTS with either a prior history of MS or having developed MS while being followed for POTS. Postural orthostatic tachycardia (POTS) is defined as symptoms of orthostatic intolerance(>6 months) accompanied by a heart rate increase of at least 30 beats/min (or a rate that exceeds 120 beats/min) that occurs in the first 10 minutes of upright posture or head up tilt test (HUTT) occurring in the absence of other chronic debilitating disorders. We identified nine patients with POTS who were suffering from MS as well. Each of these patients had been referred from various other centers for second opinions. RESULTS: The mean age at the time of diagnosis of POTS was 49+/ 9 years and eight of the 9 patients were women. Five patients (55%) had hyperlipidemia, 3 (33%) migraine and 2 (22%) patients had coronary artery disease and diabetes each. Fatigue and palpitations (on assuming upright posture) were the most common finding in our patients (9/9). All patients also had orthostatic dizziness. Syncope was seen in 5/9(55%) of patients. Four patients (44%), who did not have clear syncope, were having episodes of near syncope. The presence of POTS in our study population resulted in substantial limitation of daily activities. Following recognition and treatment of POTS, 6/9(66%), patients were able to resume daily activities of living. Their symptoms (especially fatigue and orthostatic intolerance) improved. The frequency and severity of syncope also improved. Three (33%) patients failed to show a good response to treatment. CONCLUSION: Patients suffering from MS may manifest autonomic dysfunction by developing POTS. Early recognition and proper management may help improve the symptoms of POTS. PMID- 20309395 TI - An Electrode Array for Limiting Blood Loss During Liver Resection: Optimization via Mathematical Modeling. AB - Liver resection is the current standard treatment for patients with both primary and metastatic liver cancer. The principal causes of morbidity and mortality after liver resection are related to blood loss (typically between 0.5 and 1 L), especially in cases where transfusion is required. Blood transfusions have been correlated with decreased long-term survival, increased risk of perioperative mortality and complications. The goal of this study was to evaluate different designs of a radiofrequency (RF) electrode array for use during liver resection. The purpose of this electrode array is to coagulate a slice of tissue including large vessels before resecting along that plane, thereby significantly reducing blood loss. Finite Element Method models were created to evaluate monopolar and bipolar power application, needle and blade shaped electrodes, as well as different electrode distances. Electric current density, temperature distribution, and coagulation zone sizes were measured. The best performance was achieved with a design of blade shaped electrodes (5 x 0.1 mm cross section) spaced 1.5 cm apart. The electrodes have power applied in bipolar mode to two adjacent electrodes, then switched sequentially in short intervals between electrode pairs to rapidly heat the tissue slice. This device produces a ~1.5 cm wide coagulation zone, with temperatures over 97 masculineC throughout the tissue slice within 3 min, and may facilitate coagulation of large vessels. PMID- 20309396 TI - Preparation, characterization, and in vitro release study of albendazole encapsulated nanosize liposomes. AB - The purpose of the present study was to formulate effective and controlled release albendazole liposomal formulations. Albendazole, a hydrophobic drug used for the treatment of hydatid cysts, was encapsulated in nanosize liposomes. Rapid evaporation method was used for the preparation of albendazole-encapsulated conventional and PEGylated liposomes consisting of egg phosphatidylcholine (PC) and cholesterol (CH) in the molar ratios of (6:4) and PC:CH: polyethylene glycol (PEG) (5:4:1), respectively. In this study, PEGylated and conventional liposomes containing albendazole were prepared and their characteristics, such as particle size, encapsulation efficiency, and in vitro drug release were investigated. The drug encapsulation efficiency of PEGylated and conventional liposomes was 81% and 72%, respectively. The biophysical characterization of both conventional and PEG coated liposomes were done by transmission electron microscopy and UV-vis spectrophotometry. Efforts were made to study in vitro release of albendazole. The drug release rate showed decrease in albendazole release in descending order: free albendazole, albendazole-loaded conventional liposomes, and least with albendazole-loaded PEG-liposomes. Biologically relevant vesicles were prepared and in vitro release of liposome-entrapped albendazole was determined. PMID- 20309397 TI - Effect of Fe(3)O(4)-magnetic nanoparticles on acute exercise enhanced KCNQ(1) expression in mouse cardiac muscle. AB - While the potential impact of magnetic nanoparticles (MNPs) has been widely explored in almost all medical fields, including cardiology, one question remains; that is whether MNPs interfere with cardiac physiological processes such as the expression and function of ion channels, especially in vivo. KCNQ(1) channels are richly expressed in cardiac myocytes and are critical to the repolarization of cardiac myocytes. In this study, we evaluated the effects of Fe(3)O(4)-magnetic nanoparticles (MNPs-Fe(3)O(4)) on the expression of KCNQ(1) in cardiac muscle of mice at rest and at different times following a single bout of swimming (SBS). Firstly, we demonstrated that the expression levels of KCNQ(1) channels are significantly up-regulated in mice following a SBS by means of reverse transcription polymerase chain reaction (RT-PCR) and western-blot. After treating mice with normal saline or pure MNPs-Fe(3)O(4) separately, we studied the potential effect of MNPs-Fe(3)O(4) on the expression profile of KCNQ(1) in mouse cardiac muscle following a SBS. A SBS increased the transcription of KCNQ(1) at 3 hours post exercise (3PE) 164% +/- 24% and at 12 hours post exercise (12PE) by 159% +/- 23% (P < 0.05), and up-regulated KCNQ(1) protein 161% +/- 27% at 12PE (P < 0.05) in saline mice. In MNPs-Fe(3)O(4) mice, KCNQ(1) mRNA increased by 151% +/- 14% and 147% +/- 12% at 3 and 12 PE, respectively (P <0.05). Meanwhile, an increase of 152% +/- 14% in KCNQ(1) protein was also detected at by 12PE. These results indicated that the administration of MNPs-Fe(3)O(4) did not cause any apparent effects on the expression profile of KCNQ(1) in rested or exercised mice cardiac muscle. Our studies suggest a novel path of KCNQ(1) current adaptations in the heart during physical exercise and in addition provide some useful information for the biomedical application of MNPs which are imperative to advance nanomedicine. PMID- 20309399 TI - The investigation of polymer-siRNA nanoparticle for gene therapy of gastric cancer in vitro. AB - Small interfering RNA (siRNA) molecules have significant therapeutic promise for the genetic treatment of cancer. To overcome instability and low transfection efficiency, polyethylene glycol-polyethyleneimine (PEG-PEI) was synthesized and investigated as a non-viral carrier of siRNA targeting CD44v6 in gastric carcinoma cells. The size, surface charge using zeta potential, and morphology via scanning electron microscopy (SEM) of PEG-PEI/siRNA nanoparticles was characterized, and their cytotoxicity, transfection efficiency, and interaction with SGC7901 human gastric carcinoma cells was evaluated. The transfection efficiency of PEG-PEI/siRNA nanocomplexes was dependant on the charge ratio between amino groups of PEG-PEI and phosphate groups of siRNA (N/P) values, which reflected the molar ratio of PEG-PEI to siRNA during complex formation. The transfection efficiency of PEG-PEI/siRNA at N/P 15 was 72.53% +/- 2.38%, which was higher than that observed using Lipofectamine 2000 and PEI as delivery carriers. Cytotoxicity of PEG-PEI was determined by MTT (3-[4,5-dimethylthiazol-2 yl]-2,5-diphenyltetrazolium bromide) assay and was obviously lower than that of PEI. Moreover, when N/P was below 15, PEG-PEI/siRNA was less toxic than Lipofectamine 2000/siRNA. RT-PCR (real time polymerase chain reaction) and Western blot analyses of CD44v6 expression demonstrated the gene silencing effect of PEG-PEI/siRNA at N/P 15. These data indicate that PEG-PEI may be a promising non-viral carrier for altering gene expression in the treatment of gastric cancer with many advantages, such as relatively high gene transfection efficiency and low cytotoxicity. PMID- 20309398 TI - Combination of calcipotriol and methotrexate in nanostructured lipid carriers for topical delivery. AB - The combination of calcipotriol with methotrexate can strengthen the topical therapy for psoriasis. The aim of the present study was to evaluate the potential of nanostructured lipid carriers (NLCs) loaded with lipophilic calcipotriol and hydrophilic methotrexate as topical therapy. NLCs composed of Precirol ATO 5 with various amounts of squalene as the liquid lipid were prepared. The particle size, surface charge, molecular environment, drug permeation, and skin irritation of the carriers were assessed. Hyperproliferative skin was also used as a permeation barrier in this study. It was found that variations in the Precirol/squalene ratio had profound effects on the physicochemical characteristics of the NLCs. The range of particle size of the NLC preparations was 270 to 320 nm, with vehicles containing a higher Precirol amount exhibiting a larger diameter. NLCs with a higher Precirol/squalene ratio also showed greater polarity in their molecular environment. Calcipotriol-loaded NLC systems provided drug fluxes of 0.62 to 1.08 microg/cm(2)/h, which were slightly higher or comparable to the 30% ethanol vehicle (control, 0.72 microg/cm(2)/h). The methotrexate amount permeating the skin was 2.4 to 4.4-times greater using NLCs compared to that with the control. Dual drug-loaded NLCs exhibited reduced skin permeation of calcipotriol but not methotrexate. The in vivo topical delivery examined by confocal laser scanning microscopy (CLSM) showed a good correlation with the in vitro results. These two drugs with extremely different polarities can successfully be combined in NLCs. Results suggest that NLCs may have the potential to serve as delivery carriers for antipsoriatic drugs because of enhanced drug permeation and limited skin irritation. PMID- 20309401 TI - Novel USH2A compound heterozygous mutations cause RP/USH2 in a Chinese family. AB - PURPOSE: To identify the disease-causing gene in a four-generation Chinese family affected with retinitis pigmentosa (RP). METHODS: Linkage analysis was performed with a panel of microsatellite markers flanking the candidate genetic loci of RP. These loci included 38 known RP genes. The complete coding region and exon-intron boundaries of Usher syndrome 2A (USH2A) were sequenced with the proband DNA to screen the disease-causing gene mutation. Restriction fragment length polymorphism (RFLP) analysis and direct DNA sequence analysis were done to demonstrate co-segregation of the USH2A mutations with the family disease. One hundred normal controls were used without the mutations. RESULTS: The disease causing gene in this Chinese family was linked to the USH2A locus on chromosome 1q41. Direct DNA sequence analysis of USH2A identified two novel mutations in the patients: one missense mutation p.G1734R in exon 26 and a splice site mutation, IVS32+1G>A, which was found in the donor site of intron 32 of USH2A. Neither the p.G1734R nor the IVS32+1G>A mutation was found in the unaffected family members or the 100 normal controls. One patient with a homozygous mutation displayed only RP symptoms until now, while three patients with compound heterozygous mutations in the family of study showed both RP and hearing impairment. CONCLUSIONS: This study identified two novel mutations: p.G1734R and IVS32+1G>A of USH2A in a four generation Chinese RP family. In this study, the heterozygous mutation and the homozygous mutation in USH2A may cause Usher syndrome Type II or RP, respectively. These two mutations expand the mutant spectrum of USH2A. PMID- 20309402 TI - Analysis of microsatellite polymorphisms within the GLC1F locus in Japanese patients with normal tension glaucoma. AB - PURPOSE: To investigate whether the GLC1F locus is associated with normal tension glaucoma (NTG) in Japanese patients. METHODS: We recruited 242 unrelated Japanese subjects, including, 141 NTG patients and 101 healthy controls. The patients exhibiting a comparatively early onset were selected as they suggest that genetic factors may show stronger involvement. Genotyping and assessment of allelic diversity was performed on 11 highly polymorphic microsatellite markers in and around the GLC1F locus. RESULTS: Individuals carrying the 163 allele of D7S1277i had a statistically significant increased risk of NTG (p=0.0013, pc=0.016, OR=2.47, 95%CI=1.42-4.30). None of the other markers identified significant loci (pc>0.05) after Bonferroni's correction. CONCLUSIONS: These findings suggested that the genes in the GLC1F locus may be associated with the pathogenesis of NTG. PMID- 20309404 TI - The UNITAID Patent Pool Initiative: Bringing Patents Together for the Common Good. AB - Developing and delivering appropriate, affordable, well-adapted medicines for HIV/AIDS remains an urgent challenge: as first-line therapies fail, increasing numbers of people require costly second-line therapy; one-third of ARVs are not available in pediatric formulations; and certain key first- and second-line triple fixed-dose combinations do not exist or sufficient suppliers are lacking. UNITAID aims to help solve these problems through an innovative initiative for the collective management of intellectual property (IP) rights - a patent pool for HIV medicines. The idea behind a patent pool is that patent holders - companies, governments, researchers or universities - voluntarily offer, under certain conditions, the IP related to their inventions to the patent pool. Any company that wants to use the IP to produce or develop medicines can seek a license from the pool against the payment of royalties, and may then produce the medicines for use in developing countries (conditional upon meeting agreed quality standards). The patent pool will be a voluntary mechanism, meaning its success will largely depend on the willingness of pharmaceutical companies to participate and commit their IP to the pool. Generic producers must also be willing to cooperate. The pool has the potential to provide benefits to all. PMID- 20309403 TI - Variable phenotypic expressivity in a Swiss family with autosomal dominant retinitis pigmentosa due to a T494M mutation in the PRPF3 gene. AB - PURPOSE: To characterize the clinical, psychophysical, and electrophysiological phenotypes in a five-generation Swiss family with dominantly inherited retinitis pigmentosa caused by a T494M mutation in the Precursor mRNA-Processing factor 3 (PRPF3) gene, and to relate the phenotype to the underlying genetic mutation. METHODS: Eleven affected patients were ascertained for phenotypic and genotypic characterization. Ophthalmologic evaluations included color vision testing, Goldmann perimetry, and digital fundus photography. Some patients had autofluorescence imaging, Optical Coherence Tomography, and ISCEV-standard full field electroretinography. All affected patients had genetic testing. RESULTS: The age of onset of night blindness and the severity of the progression of the disease varied between members of the family. Some patients reported early onset of night blindness at age three, with subsequent severe deterioration of visual acuity, which was 0.4 in the best eye after their fifties. The second group of patients had a later onset of night blindness, in the mid-twenties, with a milder disease progression and a visual acuity of 0.8 at age 70. Fundus autofluorescence imaging and electrophysiological and visual field abnormalities also showed some degree of varying phenotypes. The autofluorescence imaging showed a large high density ring bilaterally. Myopia (range: -0.75 to -8) was found in 10/11 affected subjects. Fundus findings showed areas of atrophy along the arcades. A T494M change was found in exon 11 of the PRPF3 gene. The change segregates with the disease in the family. CONCLUSIONS: A mutation in the PRPF3 gene is rare compared to other genes causing autosomal dominant retinitis pigmentosa (ADRP). Although a T494M change has been reported, the family in our study is the first with variable expressivity. Mutations in the PRPF3 gene can cause a variable ADRP phenotype, unlike in the previously described Danish, English, and Japanese families. Our report, based on one of the largest affected pedigree, provides a better understanding as to the phenotype/genotype description of ADRP caused by a PRPF3 mutation. PMID- 20309405 TI - No Higher Risk of CRPS After External Fixation of Distal Radial Fractures - Subgroup Analysis Under Randomised Vitamin C Prophylaxis. AB - Operative and conservative treatment of wrist fractures might lead to complex regional pain syndrome (CRPS) type I.In our multicenter dose response study in which patients with distal radial fractures were randomly allocated to placebo or vitamin C in a daily dose of 200mg, 500mg or 1500mg during 50 days, an operated subgroup was analyzed.48 (of 427) fractures) were operated (11.2%). Twenty-nine patients (60%) were treated with external fixation, 14 patients (29%) with K wiring according to Kapandji and five patients (10%) with internal plate fixation. The 379 remaining patients were treated with a plaster.In the operated group of patients who received vitamin C no CRPS (0/37) was seen in comparison with one case of CRPS (Kapandji technique) in the operated group who received placebo (1/11 = 9%, p=.23). There was no CRPS after external fixation.In the conservatively treated group 17 cases of CRPS (17/379 = 4.5%) occurred in comparison with one in case of CRPS in the operated group (1/48 = 2.1%, p=.71).External fixation doesn't necessarily lead to a higher incidence of CRPS in distal radial fractures. Vitamin C may also play a role in this. This subgroup analysis in operated distal radial fractures showed no CRPS occurrence with vitamin C prophylaxis. PMID- 20309406 TI - Primary shoulder arthroplasty versus conservative treatment for comminuted proximal humeral fractures: a systematic literature review. AB - The objective was to identify whether arthroplasty or conservative treatment is the best available treatment for three- and four-part proximal humeral fractures by analyzing the outcome measure of the Constant score. We conducted an electronic search. The systematic review included 33 studies encompassing 1096 patients with three- or four-part proximal humeral fractures that used the Constant score as outcome measure. The mean Constant score in the conservative group was 66.5 and in the arthroplasty group was 55.5. The difference could be attributed to selection bias, unreliable classification of the fractures and inter-observer differences in the assessment of the Constant score. PMID- 20309407 TI - Rare Lipomatous Tumors with Osseous and/or Chondroid Differentiation in the Oral Cavity Report of Two Cases and Review of the Literature. AB - The purpose of this study was to determine the clinicopathological and immunohistochemical features of lipoma/fibrolipoma with rare occasions as osseous and/or chondroid differentiation in the oral cavity. Two cases of the tumors, who presented with a painless, relatively hard mass on the oral mucosa, were studied. These were consisted of a well-circumscribed mass of fatty tissue with chondroid and significant fibrous component intermixed with the lobules of fat cells with chondroid and woven bone component, respectively. Immunohistochemical study revealed that peripheral spindle cells around chondroid tissue stained diffusely for S-100 alpha & beta and Sox-9, though peripheral spindle cells around osteoid tissue only stained for RUNX-2. According to review of the literature, lipoma/fibrolipoma with osseous and/or chondroid differentiation was 18 cases. Also fibrolipoma with osseous and chondroid differentiation is the first to be reported here. These results indicated that the cartilage/bone is produced by differentiation of undifferentiated mesenchymal cells of stroma. PMID- 20309409 TI - Effect of educational level on oral health in peritoneal and hemodialysis patients. AB - Background. In previous studies, the oral and dental health statuses were compared in hemodialysis (HD) and peritoneal dialysis (PD) patients without taking into account the effect of educational levels on oral health. Hence we aimed to make a comparison of these parameters based upon the subjects educational levels. Patients and Methods. 76 PD (33 males, 43 females-mean age: 44 +/- 12 years) and 100 HD (56 males, 44 females-mean age: 46 +/- 14 years) patients were included. The number of decayed, missing and filled teeth were detected, DMFT index was calculated and plaque index (PI) values were assessed. Results. Significantly higher numbers of filled teeth (P < .001) and lower PI values (P < .01) in the PD group were detected with higher educational levels, whereas no significance was detected in the HD group. Higher DMFT index values were assessed in the lower educated and high school levels in PD than HD patients (P < .05). Higher numbers of filled teeth (P < .05) were detected in the secondary school level in PD patients. This difference was even more significant in the high school level (P < .001). Conclusion. We assume that PD patients, who were found to be in a higher educational level, are more caring for their oral health as compared to HD patients. PMID- 20309408 TI - Restoration of endodontically treated teeth review and treatment recommendations. AB - Coronal restorations and posts can positively influence the long-term prognosis of teeth following root canal therapy. Final sealing the canal by placing an appropriate post and core will minimize leakage of oral fluids and bacteria into the periradicular area and is recommended as soon as possible after completion of root canal filling. Glass ionomer or MTA placed over the residual root canal filling after post space preparation may be effective to prevent bacterial leakage. A ferrule of 1-2 mm of tooth tissue coronal to the finish line of the crown significantly improves the fracture resistance of the tooth and is more important than the type of the material the core and post are made of. PMID- 20309410 TI - Correlation of hepatitis C antibody levels in gingival crevicular fluid and saliva of hepatitis C seropositive hemodialysis patients. AB - Search for hepatitis C virus (HCV) in body fluids other than blood is important when assessing possible nonparenteral routes of viral transmission. However, the role of oral fluids in HCV transmission remains controversial. Our aim was to compare the prevalence of HCV antibody (HCV Ab) levels in saliva, and gingival crevicular fluid (GCF) of HCV seropositive hemodialysis patients. Serum, saliva and GCF samples were collected from thirty-nine patients. Samples were analyzed for HCV Ab using the Ortho HCV 3.0 SAVe enzyme-linked immunosorbent assay (ELISA). HCH Ab levels in saliva and GCF of all HCV-seropositive patients were statistically compared. Reported here are the results of the study designed to determine the correlation between HCV-RNA positivity in serum and the detection of antibodies in GCF and saliva. One hundred percent (100%) of the 39 patients have antibodies to HCV in their serum, 15.4% have antibodies to HCV in GCF, and saliva found out. HCV Ab seropositivity in GCF and saliva was significantly correlated (kappa = 0.462; P < .001). This study supports the concept that GCF may be a significant source of HCV in saliva. PMID- 20309411 TI - Determination of cortisol and dehydroepiandrosterone levels in saliva for screening of periodontitis in older Japanese adults. AB - Background. Recent reports have found a positive relationship between periodontitis and the hormones cortisol and dehydroepiandrosterone (DHEA). We investigated the associations between those levels and periodontitis in never smokers and smokers of elderly subjects. Subjects and Methods. Cortisol and DHEA levels in saliva were determined in 171 subjects (85 males, 86 females), with clinical examinations including probing depth (PD) and clinical attachment loss (CAL) also performed. Results. Smoking had effects on cortisol and DHEA levels, and those were significantly associated with severe PD and CAL in never-smokers. According to ROC analysis, the cutoff values of cortisol and DHEA to obtain the optimal sensitivity and specificity for detecting severe periodontitis were 2.06 ng/mL and 60.24 pg/mL, respectively, for PD, and 2.12 ng/mL and 61.78 pg/mL, respectively, for CAL. Conclusions. Assessment of hormone levels may be a useful screening method for periodontitis, though limited to never-smokers. PMID- 20309412 TI - Comparison of the Keratometric Corneal Astigmatic Power after Phacoemulsification: Clear Temporal Corneal Incision versus Superior Scleral Tunnel Incision. AB - Objective. This is prospective randomized control trial to compare the mean keratometric corneal astigmatism diopter power (not surgical induced astigmatism) among preop and one-month and three-month postop phacoemulcification of either a clear temporal corneal incision or a superior scleral tunnel Incision, using only keratometric astigmatic power reading to evaluate the difference between the two cataract surgery incisions. Methods. 120 patients (134 eyes) underwent phacoemulcification were randomly assigned to two groups: Group A, the clear temporal corneal incision group, and Group B, the superior scleral tunnel incision group. SPSS11.5 Software was used for statistical analysis to compare the postsurgical changes of cornea astigmatism on keratometry. Results. The changes of corneal astigmatic diopter in Groups A and B after 3 month postop from keratometric reading were 1.04 + 0.76 and 0.94 + 0.27, respectively (P = .84 >.05), which showed no statistic significance difference. Conclusion. The incision through either temporal clear cornea or superior scleral tunnel in phacoemulcification shows no statistic difference in astigmatism change on keratometry 3-month postop. PMID- 20309413 TI - Undiagnosed patent foramen ovale presenting as retinal artery occlusion-an emerging association. AB - Purpose. To report patent foramen ovale (PFO) as the cause of retinal artery occlusion in a young and previously fit male and discuss the appropriate medical and surgical management options. Methods. Interventional case report with serial fundus photographs of an 18-year-old male presenting to the eye casualty with sudden onset left visual loss. Results. Visual acuities were 6/24 left and 6/4 right with a left afferent pupillary defect. Slitlamp examination confirmed a left hemiretinal artery occlusion and subsequent cardiology review with transoesophageal echocardiography revealed patent foramen ovale which was closed surgically. Conclusions. PFO is not uncommon and is often covert but predisposes individuals to embolic events. These events may be ophthalmic with visual sequelae and so ophthalmologists, physicians, and other healthcare personnel should be aware of this important and emerging association. PMID- 20309414 TI - Secretory Leukoprotease Inhibitor: A Native Antimicrobial Protein in the Innate Immune Response in a Rat Model of S. aureus Keratitis. AB - Purpose. To describe the presence of secretory leukocyte protease inhibitor (SLPI), a cationic peptide with antimicrobial and antiprotease activity in the innate immune reaction in a rat model of Staphylococcus aureus keratitis. Methods. Forty female Lewis rats were divided into 2 groups: the infectious keratitis and the epithelial defect groups. Eyes were processed for immunohistochemical studies for SLPI, interleukin-1, interleukin-6, tumor necrosis factor-alpha, and matrix metalloproteinase-8. Results. Immunohistochemical studies confirmed high levels of SLPI, IL-1, IL-6, TNF-alpha, and MMP-8 expression in eyes with S. aureus keratitis and with epithelial defects, in contrast to undetectable SLPI expression in the normal control corneas. Conclusions. To our knowledge, this paper is the first to demonstrate the presence of SLPI with increased amounts of proinflammatory cytokines in inflamed and infected corneas. PMID- 20309415 TI - Normal speed and accuracy of saccade and vergence eye movements in dyslexic reader children. AB - Objective. Latency of eye movements depends on cortical structures while speed of execution and accuracy depends mostly on subcortical brainstem structures. Prior studies reported in dyslexic reader children abnormalities of latencies of saccades (isolated and combined with vergence); such abnormalities were attributed to deficits of fixation control and of visual attention. In this study we examine speed and accuracy characteristics of horizontal eye movements in natural space (saccades, vergence and combined movements) in dyslexic reader children. Methods. Two paradigms are tested: gap paradigm (fixation offset 200 ms prior to target onset), producing shorter latencies, in both non-dyslexic reader and dyslexic reader children and simultaneous paradigm. Seventeen dyslexic reader children (mean age: 12 +/- 0.08 years) and thirteen non-dyslexic reader children (mean age: 12 +/- 1 years) were tested. Horizontal eye movements from both eyes were recorded simultaneously by a photoelectric device (Oculometer, Dr. Bouis). Results. For all movements tested (saccades, vergence, isolated or combined) and for both paradigms, the mean velocity and accuracy were similar in dyslexic readers and non-dyslexic readers; no significant difference was found. Conclusion. This negative but important result, suggests no dysfunction of brainstem ocular motor circuits in dyslexic readers. It contrasts results on latencies related to visual attention dysfunction at cortical level. PMID- 20309416 TI - Contribution of a real depth distance stereoacuity test to clinical management. AB - Measurement of Stereopsis forms an important part of the clinical assessment of patients with disorders of ocular motility. The introduction of a real depth distance stereoacuity test (FD2) was evaluated in clinical practice and to what extent the introduction affected clinical management. Seventy-three patients under evaluation before and following the introduction of the test were included. Combined thresholds were measured at near using the Frisby and TNO test and at distance using the FD2. Fifty healthy controls were included. Forty-five patients demonstrated Stereopsis using the FD2 and 23 of these had a change in their management based in part on their responses using the FD2. Patients with evidence of Stereopsis using the FD2 were significantly more likely to have change in their management than expected from the whole sample (P = .02). The introduction of a real depth distance stereoacuity test into clinical practice contributed to a change in management when used in conjunction with other tests. The usefulness of the FD2 is limited by its range at 6 m. Use at closer distances necessitates the calculation of binocular threshold from the combined and monocular threshold. PMID- 20309417 TI - Stigma of People with HIV/AIDS in Sub-Saharan Africa: A Literature Review. AB - The aim of this literature review is to elucidate what is known about HIV/AIDS and stigma in Sub-Saharan Africa. Literature about HIV/AIDS and stigma in Sub Saharan Africa was systematically searched in Pubmed, Medscape, and Psycinfo up to March 31, 2009. No starting date limit was specified. The material was analyzed using Gilmore and Somerville's (1994) four processes of stigmatizing responses: the definition of the problem HIV/AIDS, identification of people living with HIV/AIDS (PLWHA), linking HIV/AIDS to immorality and other negative characteristics, and finally behavioural consequences of stigma (distancing, isolation, discrimination in care). It was found that the cultural construction of HIV/AIDS, based on beliefs about contamination, sexuality, and religion, plays a crucial role and contributes to the strength of distancing reactions and discrimination in society. Stigma prevents the delivery of effective social and medical care (including taking antiretroviral therapy) and also enhances the number of HIV infections. More qualitative studies on HIV/AIDS stigma including stigma in health care institutions in Sub-Saharan Africa are recommended. PMID- 20309418 TI - Infant sleeping environment in South-eastern Nigeria (sleeping place and sleeping position): a preliminary survey. AB - Objective. To determine infant sleeping position/place and the factors associated with them in South-eastern Nigeria. Methods. this is a cross-sectional study on infant sleeping environment. Subjects were the mother/ infant pairs that attended the well baby clinics at the Institute of Child Health of the University of Nigeria Teaching Hospital, Enugu (ICH-UNTH), Mother of Christ Specialist Hospital (MCSH), Enugu and the Ebonyi State University Teaching Hospital (EBSUTH), Abakaliki. Results. Lying on the side was the most common (51.1%) and the least stable sleeping position. Only 36.6% of infants who slept in that position were likely to be found in the same position the following morning; lying supine was the most stable (74.1%). The difference in stability of sleeping positions was statistically significant (P < .01). Twenty six point seven percent of the mothers routinely lay their infants in prone position. On logistic regression, maternal parity was the only factor that was predictive of nonprone sleeping position (P = .01). Bed sharing, though common (66.9%), was more among the experienced (P = .03) and less educated mothers (P < .01). Conclusion. There is a high level of prone sleeping position and bed sharing among infants in this study site. The potential consequences of these are unclear. There is therefore a need to conduct local studies to clarify its implication. PMID- 20309419 TI - Front-loading sputum microscopy services: an opportunity to optimise smear-based case detection of tuberculosis in high prevalence countries. AB - Setting. Ethiopia, Nepal, Nigeria, and Yemen. Objective. To reduce the time to complete sputum microscopy. Design. Cross-sectional surveys enrolling 923 patients with chronic cough in the 4 countries and using similar protocols. Spot morning-spot sputum specimens were collected. An additional sputum specimen (Xspot) was collected one hour after the first, and the yields of the first two or the three specimens collected as spot-morning-spot or spot-Xspot-morning were compared. Results. 216 patients had >/= one positive smear. 210 (97%) were identified by the spot-morning-spot, and 210 (97%) were identified by the spot Xspot-morning specimens, with 203 and 200 identified by the first 2 specimens of each approach, respectively. Neither difference was significant. Conclusions. The time to complete smear microscopy could be reduced. PMID- 20309420 TI - Factors associated with coverage and usage of long-lasting insecticidal nets in madagascar. AB - In October 2007, long-lasting insecticidal nets (LLINs) were distributed in 59 of the 111 districts in Madagascar as part of a nationwide child survival campaign. A community-based cross-sectional survey was conducted six months post-campaign to evaluate net ownership, use and equity. Here, we examined the effects of socioeconomic factors on LLIN ownership and usage in districts with and without net distribution during the campaign. Our data demonstrated that in districts with LLIN distribution, LLIN ownership was similar across all wealth groups in households with at least one child under the age of five years (90.5% versus 88.6%); in districts without net distribution, 57.8% of households in the poorest tertile compared to 90.1% of households in the least poor tertile owned at least one LLIN. In contrast, in LLIN-owning households, both in districts with and without net distribution, higher socio-economic status was not associated with use among children under five years. These findings suggest that socio-economic status contributes to the household net ownership but once a household owns a net, socio-economic status is not associated with net use. PMID- 20309421 TI - Simple Liver Cyst as a Focus of Salmonella paratyphi Abscess: A Case Report. AB - Salmonellosis, endemic in various part of the world, is considered a differential diagnosis in a tropical traveller. Although it usually presents as gastroenteritis, its various clinical syndromes may vary from mild gastroenteritis to severe septicaemia including abscess formation, the later two being the most common cause of morbidity and mortality. Here we present a patient who returned to the UK after an overseas trip and was diagnosed with a pyogenic liver abscess with Salmonella paratyphi at a site of a pre-existing simple liver cyst. PMID- 20309422 TI - Journal of Hematopathology listed in PubMed! PMID- 20309423 TI - Recent advances in bone marrow biopsy pathology. AB - The second quarter of 2009 saw steady advances in bone marrow biopsy (BMB) pathology. The following publications are a personal selection of the highlights. Quality issues in diagnostic immunohistochemistry for BMB have largely been ignored in external quality assurance programmes, and this issue is highlighted. In other areas, publications reflecting advances in flow cytometry and aspirate morphology are discussed where translation to the BMB is possible. Classifications undergo constant change, and several publications address the redefinition of the cut off points between malignancy, benign, and normal. Lastly, current scientific research is presented where it is relevant to the understanding of BMB pathobiology. PMID- 20309424 TI - Carcinoma and multiple lymphomas in one patient: establishing the diagnoses and analyzing risk factors. AB - Multiple malignancies may occur in the same patient, and a few reports describe cases with multiple hematologic and non-hematologic neoplasms. We report the case of a patient who showed the sequential occurrence of four different lymphoid neoplasms together with a squamous cell carcinoma of the lung. A 62-year-old man with adenopathy was admitted to the hospital, and lymph node biopsy was positive for low-grade follicular lymphoma. He achieved a partial remission with chemotherapy. Two years later, a PET-CT scan showed a left hilar mass in the lung; biopsy showed a squamous cell carcinoma. Simultaneously, he was diagnosed with diffuse large B cell lymphoma in a neck lymph node; after chemo- and radiotherapy, he achieved a complete response. A restaging PET-CT scan 2 years later revealed a retroperitoneal nodule, and biopsy again showed a low-grade follicular lymphoma, while a biopsy of a cutaneous scalp lesion showed a CD30 positive peripheral T cell lymphoma. After some months, a liver biopsy and a right cervical lymph node biopsy showed a CD30-positive peripheral T cell lymphoma consistent with anaplastic lymphoma kinase-negative anaplastic large cell lymphoma. Flow cytometry and cytogenetic and molecular genetic analysis performed at diagnosis and during the patient's follow-up confirmed the presence of two clonally distinct B cell lymphomas, while the two T cell neoplasms were confirmed to be clonally related. We discuss the relationship between multiple neoplasms occurring in the same patient and the various possible risk factors involved in their development. PMID- 20309426 TI - Hematopathology: a decade into the new millennium. PMID- 20309425 TI - New developments in the pathology of malignant lymphoma: a review of the literature published from January to August 2009. PMID- 20309427 TI - A cytomorphological and immunohistochemical profile of aggressive B-cell lymphoma: high clinical impact of a cumulative immunohistochemical outcome predictor score. AB - We analyzed morphological and immunohistochemical features in 174 aggressive B cell lymphomas of nodal and extranodal origin. Morphological features included presence or absence of a follicular component and cytologic criteria according to the Kiel classification, whereas immunohistochemical studies included expression of CD10, BCL-2, BCL-6, IRF4/MUM1, HLA-DR, p53, Ki-67 and the assessment of plasmacytoid differentiation. Patients were treated with a CHOP-like regimen. While the presence or absence of either CD10, BCL-6 and IRF4/MUM1 reactivity or plasmacytoid differentiation did not identify particular cytomorphologic or site specific subtypes, we found that expression of CD10 and BCL-6, and a low reactivity for IRF4/MUM1 were favourable prognostic indicators. In contrast, BCL 2 expression and presence of a monotypic cytoplasmic immunoglobulin expression was associated with an unfavourable prognosis in univariate analyses. Meta analysis of these data resulted in the development of a cumulative immunohistochemical outcome predictor score (CIOPS) enabling the recognition of four distinct prognostic groups. Multivariate analysis proved this score to be independent of the international prognostic index. Such a cumulative immunohistochemical scoring approach might provide a valuable alternative in the recognition of defined risk types of aggressive B-cell lymphomas. PMID- 20309428 TI - P38 mitogen activated protein kinase expression and regulation by interleukin-4 in human B cell non-Hodgkin lymphomas. AB - The prevalence and regulation of p38 mitogen activated protein kinase (MAPK) expression in human lymphomas have not been extensively studied. In order to elucidate the role of p38 MAPK in lymphomagenesis, we examined the expression of native and phosphorylated p38 (p-p38) MAPK in cell lines derived from human hematopoietic neoplasms including B cell lymphoma-derived cell lines using Western blot analysis. The p-p38 MAPK protein was also analyzed in 30 B cell non Hodgkin lymphoma (NHL) tissue biopsies by immunohistochemistry. Our results show that the expression of p38 MAPK was up-regulated in most of the cell lines as compared with peripheral blood lymphocytes, while the expression of p-p38 MAPK was more variable. A subset of B cell NHL biopsies showed increased expression of p-p38 MAPK relative to reactive germinal center cells. Interleukin-4 (IL-4) induced a dose-dependent increase in the expression of p-p38 MAPK (1.6- to 2.8 fold) in cell lines derived from activated B cell-like diffuse large B cell lymphoma (DLBCL) but not those from germinal center-like DLBCL. No change was seen in native p38 MAPK. The in vitro kinase activity of p38 MAPK, however, was induced (1.6- to 3.2-fold) in all five cell lines by IL-4. Quantitative fluorescent RT-PCR demonstrated that all four isoforms of p38 MAPK gene were expressed in the lymphoma cell lines, with p38gamma and p38beta isoforms being predominant. IL-4 stimulation increased the expression of beta, gamma, and delta isoforms but not alpha isoform in two cell lines. In conclusion, there is constitutive expression and activation of p38 MAPK in a large number of B lymphoma-derived cell lines and primary lymphoma tissues, supportive of its role in lymphomagenesis. The differential IL-4 regulation of p38 MAPK expression in cell lines derived from DLBCL may relate to the cellular origin of these neoplasms. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s12308-009-0049-5) contains supplementary material, which is available to authorized users. PMID- 20309429 TI - Changed concepts and definitions of myeloproliferative neoplasms (MPN), myelodysplastic syndromes (MDS) and myelodysplastic/myeloproliferative neoplasms (MDS/MPN) in the updated 2008 WHO classification. AB - The purpose of this overview is to discuss the changes in the 2008 WHO classification of myeloid neoplasms, with exclusion of acute myeloid leukaemia. Specific mutations or rearrangements leading to constitutive activation of growth factor receptors or cytoplasmic tyrosine kinases are now recognised as recurrent genetic events characterising the group of myeloproliferative neoplasms (MPN). A newly introduced subgroup consists of patients with persistent eosinophilia and myeloid or lymphoid proliferations harbouring specific genetic changes involving platelet-derived growth factor receptors alpha and beta (PDGFRA and PDGFRB) or fibroblast growth factor receptor 1 (FGFR1). The clinical relevance of recognising myeloid neoplasms with aberrant tyrosine kinase activity is based in novel treatment options with tyrosine kinase inhibitors. The myelodysplastic syndromes (MDS) without increased blasts are further divided into subtypes of refractory cytopaenias with unilineage dysplasia. A new provisional entity is refractory cytopaenia of childhood. Down syndrome- and therapy-related myeloid neoplasms, including MDS, were moved to the section of acute myeloid leukaemia and related precursor neoplasms. PMID- 20309431 TI - Rare lymphoid malignancies of the breast: a report of two cases illustrating potential diagnostic pitfalls. AB - Breast involvement by lymphoma is uncommon and poses challenges in diagnosis. Lymphomas may clinically, radiologically, and morphologically mimic both benign and neoplastic conditions. We describe two cases of lymphoid malignancies predominantly involving the breast, both presenting diagnostic dilemmas. The first case, ALK-negative anaplastic large-cell lymphoma involving a seroma associated with a breast implant, is an emerging clinicopathologic entity. Anaplastic large-cell lymphoma has been identified in association with breast implants and seroma formation relatively recently. The second case, hairy cell leukemia involving the breast and ipsilateral axillary sentinel lymph node, is, to our knowledge, the first reported case of hairy cell leukemia involving the breast at the time of diagnosis. While a localized bone lesion was present at time of diagnosis, bone marrow involvement was relatively mild in comparison to that seen in the breast and lymph node. In the first case, lymphoma occurred in a clinical setting where malignancy was unsuspected, highlighting the importance of careful morphologic evaluation of paucicellular samples, as well as awareness of rare clinicopathologic entities, in avoiding a misdiagnosis of a benign inflammatory infiltrate. In the second case, the lymphoid neoplasm exhibited classic morphologic and immunophenotypic features, but presented at an unusual site of involvement. Knowledge of the patient's concurrent diagnosis of hairy cell leukemia involving the bone marrow and bone helped avoid a misdiagnosis of carcinoma rather than lymphoma. PMID- 20309430 TI - Gray zones around diffuse large B cell lymphoma. Conclusions based on the workshop of the XIV meeting of the European Association for Hematopathology and the Society of Hematopathology in Bordeaux, France. AB - The term "gray-zone" lymphoma has been used to denote a group of lymphomas with overlapping histological, biological, and clinical features between various types of lymphomas. It has been used in the context of Hodgkin lymphomas (HL) and non Hodgkin lymphomas (NHL), including classical HL (CHL), and primary mediastinal large B cell lymphoma, cases with overlapping features between nodular lymphocyte predominant Hodgkin lymphoma and T-cell/histiocyte-rich large B cell lymphoma, CHL, and Epstein-Barr-virus-positive lymphoproliferative disorders, and peripheral T cell lymphomas simulating CHL. A second group of gray-zone lymphomas includes B cell NHL with intermediate features between diffuse large B cell lymphoma and classical Burkitt lymphoma. In order to review controversial issues in gray-zone lymphomas, a joint Workshop of the European Association for Hematopathology and the Society for Hematopathology was held in Bordeaux, France, in September 2008. The panel members reviewed and discussed 145 submitted cases and reached consensus diagnoses. This Workshop summary is focused on the most controversial aspects of gray-zone lymphomas and describes the panel's proposals regarding diagnostic criteria, terminology, and new prognostic and diagnostic parameters. PMID- 20309432 TI - New developments in the pathology of malignant lymphoma: a review of the literature published from August to November 2009. PMID- 20309433 TI - TRACER. A new approach to comparative modeling that combines threading with free space conformational sampling. AB - A new approach to comparative modeling of proteins, TRACER, is described and benchmarked against classical modeling procedures. The new method unifies true three-dimensional threading with coarse-grained sampling of query protein conformational space. The initial sequence alignment of a query protein with a template is not required, although a template needs to be somehow identified. The template is used as a multi-featured fuzzy three-dimensional scaffold. The conformational search for the query protein is guided by intrinsic force field of the coarse-grained modeling engine CABS and by compatibility with the template scaffold. During Replica Exchange Monte Carlo simulations the model chain representing the query protein finds the best possible structural alignment with the template chain, that also optimizes the intra-protein interactions as approximated by the knowledge based force field of CABS. The benchmark done for a representative set of query/template pairs of various degrees of sequence similarity showed that the new method allows meaningful comparative modeling also for the region of marginal, or non-existing, sequence similarity. Thus, the new approach significantly extends the applicability of comparative modeling. PMID- 20309434 TI - Effect of pentoxifylline on proteinuria, markers of tubular injury and oxidative stress in non-diabetic patients with chronic kidney disease - placebo controlled, randomized, cross-over study. AB - BACKGROUND: Inhibition of the renin-angiotensin-aldosterone system (RAAS) with angiotensin converting enzyme inhibitors (ACEI) and/or angiotensin II subtype 1 receptor antagonists (ARB) is a common strategy used in the management of patients with chronic kidney disease (CKD). However, there is no universal therapy that can stop progression of CKD. Pentoxifylline (PTE) is a non-specific phosphodiesterase inhibitor with anti-inflammatory properties. It has been reported to have promising effects in CKD treatment. METHODS: In a placebo controlled, randomized, cross-over study we evaluated the influence of PTE (1200 mg/day) added to RAAS blockade on proteinuria, surrogate markers of tubular injury and oxidative stress-dependent products in 22 non-diabetic patients with proteinuria (0.4-4.3 g per 24 h) with normal or declined kidney function [eGFR 37 178 mL/min]. In an eight-week run-in period, therapy using ACEI and/or ARB was adjusted to achieve a blood pressure below 130/80 mm Hg. Next, patients were randomly assigned to one of two treatment sequences: PTE/washout/placebo or placebo/washout/PTE. Clinical evaluation and laboratory tests were performed at the randomization point and after each period of the study. RESULTS: The PTE therapy reduced proteinuria (by 26%) as compared to placebo. There were no differences in alpha(1)-microglobulin, urine excretion of N-acetyl-beta-d glucosaminidase (NAG), hsCRP, the urinary excretion of 15-F(2)t-isoprostane, blood pressure (BP), eGFR and serum creatinine between the PTE and placebo groups. CONCLUSION: Pentoxifylline may decrease proteinuria in non-diabetic patients with CKD. PMID- 20309435 TI - Lack of correlation between X region spa polymorphism and virulence of methicillin resistant and methicillin sensitive Staphylococcus aureus strains. AB - Staphylococcus aureus is an etiological factor of severe infections in both hospital and ambulatory environments. As methicillin resistant Staphylococcus aureus strains spread quickly across healthcare centers resulting in life threatening infections with increased mortality, they are considered more virulent than MSSA strains. Protein A, encoded by the spa gene, is one of the virulence factors involved in the staphylococcal pathogenesis. It has been suggested that the number of 24-bp tandem repeat units along the X region of the spa gene correlates with the virulence level of the strains. The current work analyzed the relationships between the virulence of MRSA and MSSA strains with region X polymorphism. No obvious correlation was observed. PMID- 20309439 TI - Ambient mass spectrometry. PMID- 20309440 TI - Ambient ionization mass spectrometry: current understanding of mechanistic theory; analytical performance and application areas. AB - Ambient ionization mass spectrometry allows the rapid analysis of samples or objects in their native state in the open environment with no prior preparation. Over the past six years, the ability of these techniques to provide selective analyte desorption and ionization, in combination with mass spectrometry (MS), has provided a growing number of powerful analytical alternatives across broad application areas, both quantitative and qualitative in nature, including pharmaceutical analysis, process chemistry, biological imaging, in vivo analysis, proteomics, metabolomics, forensics, and explosives detection. With the emergence of new ambient ionization methods, and the complementary nature of existing desorption and/or ionization techniques, additional hyphenated methods have been devised, which pushes the total number of documented methods to almost thirty. To cover all current ambient ionization techniques in detail would be too complex and detract from the main objective of this review. Rather, an overview of the field of ambient ionization MS will be given, followed by broad classification to allow detailed discussion of theory and common mechanistic factors underpinning a number of key techniques. Consideration will be given to experimental design, ease of implementation and analytical performance, detailing subsequent impact on a number of application areas, both established and emerging. PMID- 20309442 TI - Selective ionization of melamine in powdered milk by using argon direct analysis in real time (DART) mass spectrometry. AB - 5-Hydroxymethylfurfural (5-HMF) is a compound with the elemental composition C(6)H(6)O(3) that is present in powdered milk. Protonated 5-HMF (calculated m/z 127.0395) has the same nominal m/z as protonated melamine (calculated m/z 127.0732) and can interfere with direct analysis of melamine in powdered milk. Tandem mass spectrometry and high-resolution mass spectrometry have been previously used to distinguish melamine from 5-HMF. An alternative approach is presented here that uses the direct analysis in real time (DART) ion source operated with argon gas in combination with acetylacetone and pyridine reagent gases to selectively ionize melamine and eliminate the interference from 5-HMF. High-resolution/accurate mass data were used to verify the elimination of the 5 HMF interference and confirm the melamine elemental composition. With further refinement, this technique could lead to a rapid analysis method for screening large numbers of samples. PMID- 20309441 TI - Desorption electrospray ionization and other ambient ionization methods: current progress and preview. AB - Mass spectrometry allows rapid chemical analysis of untreated samples in the ambient environment. This is a result of recent rapid progress in ambient ionization techniques. The most widely studied of these new methods, desorption electrospray ionization (DESI), uses fast-moving solvent droplets to extract analytes from surfaces and propel the resulting secondary microdroplets towards the mass analyzer. This review of DESI and other ambient methods centers on the accompanying chemical processes. Manipulation of the chemistry accompanying ambient ionization can be used to optimize chemical analysis, including molecular imaging. Solvent effects, geometry effects, electrochemical processes and mechanisms are covered. Extensions of the methodology to solution-phase analysis, to stand-off detection and to therapeutic drug analysis using miniature mass spectrometers are also treated. PMID- 20309443 TI - Routine analysis and characterization of highly insoluble polycyclic aromatic compounds by direct analysis in real time mass spectrometry (DART). AB - Direct Analysis in Real Time (DART), is used for the first time for the routine rapid analysis of highly insoluble polycyclic aromatic compounds. Direct analysis of such compounds as solid samples under solvent-free conditions shows that DART is a powerful analytical platform capable of providing high-throughput analysis for these complex samples, requiring no special sample pre-treatment or instrument setup. PMID- 20309444 TI - Direct analysis of melamine in complex matrices using a handheld mass spectrometer. AB - A low temperature plasma ambient ionization source, coupled to a portable mass spectrometer (Mini 10.5), is used for the determination of melamine contamination in whole milk and related materials. Thermally assisted desorption and ionization of the analyte was achieved with the plasma probe. The small size, low power consumption and capability for direct sampling without pretreatment makes plasma ionization an appropriate ionization method for use with a handheld mass spectrometer. The standard discontinuous atmospheric pressure interface used to connect atmospheric pressure ion sources to mass spectrometers (Gao et al., Anal. Chem., 2008, 80, 4026-4032) was modified by using supplementary pumping to increase the ion transfer efficiency. Whole milk, fish, milk powder and other complex matrices spiked with melamine were placed on glass slides close to the vacuum inlet and analyzed without sample pretreatment. Quantitation in complex matrices was achieved using MS/MS of protonated melamine m/z 127 to yield the characteristic fragment ion of m/z 85. Analysis rates of two samples per minute, levels of melamine as low as 250 ng/mL in whole milk (below the regulatory level in the US of 1 ppm (1 microg/mL) or the European level of 2.5 ppm (microg/mL)), a linear dynamic range of 0.5-50 microg/mL and a relative standard deviation of ca. 7.6-16.2% were achieved. The importance of melamine to public health and the prior lack of a rapid, sensitive and yet highly specific field analysis method add to the relevance of this study. PMID- 20309445 TI - Transmission-mode direct analysis in real time and desorption electrospray ionization mass spectrometry of insecticide-treated bednets for malaria control. AB - Transmission-mode direct analysis in real time (TM-DART) is presented as an alternative sampling strategy to traditional methods of sample introduction for DART MS analysis. A custom-designed sample holder was fabricated to rapidly and reproducibly position insecticide-treated nets normal to the ionizing metastable gas stream, enabling transmission of desorbed analyte ions through the holder cavity and into the MS. Introduction of the sample at this fixed geometry eliminates the need for optimizing sample position and allows spectra based on factors such as metastable gas temperature and flow to be systematically evaluated. The results presented here, supported by computational fluid dynamic simulations, demonstrate the effects of these factors on the resulting mass spectra and the potential of this sampling strategy to be used for qualitative and quantitative analyses. Transmission-mode desorption electrospray ionization (TM-DESI) experiments on similar insecticide-treated nets were performed for comparison purposes. PMID- 20309446 TI - Molecularly imprinted polymers as analyte sequesters and selective surfaces for easy ambient sonic-spray ionization. AB - The use of a molecularly imprinted polymer (MIP) as a selective surface for ambient mass spectrometry is demonstrated. The MIP is used to sequester target analytes from urine and easy ambient sonic-spray ionization mass spectrometry (EASI-MS) is shown to be able to efficiently desorb the analytes from the MIP surface and then transfer them in protonated forms to the gas phase for MS analysis. A set of five phenothiazines (chlorpromazine, perphenazine, triflupromazine, thioridazine and prochlorperazine) were chosen from a proof-of principle class of drug samples. A chlorpromazine-imprinted methacrylic polymer was synthesized and used to prepare a MIP probe. The MIP-EASI-MS technique using acidified methanol as solvent has been shown to allow quantification of all five drugs in urine with LOQ of ca. 1 micromol L(-1). PMID- 20309447 TI - Fingerprinting and aging of ink by easy ambient sonic-spray ionization mass spectrometry. AB - Using easy ambient sonic-spray ionization mass spectrometry (EASI-MS), fast and non-destructive fingerprinting identification and aging of ballpoint pen ink writings have been performed directly from paper surfaces under ordinary ambient conditions. EASI-MS data obtained directly from the ink lines showed that pens from different brands provide typical ink chemical profiles. Accelerated ink aging has also been monitored by EASI-MS revealing contrasting degradation behaviors for six different common ink dyes. As demonstrated for Basic Violet 3, some dyes display a cascade of degradation products whose abundances increase linearly with time thus functioning as 'chemical clocks' for ink aging. Analysis of questionable documents has confirmed the ink aging capabilities of EASI-MS. The order of superimposition at a crossing point has also been determined by EASI MS. For two superimposed ink lines, continuous EASI-MS analysis has also shown that the EASI spray is able to penetrate through the layers and therefore both ink layers could be characterized. PMID- 20309448 TI - Effects of matrix, electrospray solution, and laser light on the desorption and ionization mechanisms in electrospray-assisted laser desorption ionization mass spectrometry. AB - Electrospray-assisted laser desorption ionization (ELDI) is a technique which combines laser desorption with subsequent electrospray ionization. It is useful for directly detecting small and large molecules in solid or liquid samples under ambient conditions. In this paper, the detection of the protein molecules desorbed on a dry protein spot by using pulse laser energies of up to 300 microJ was demonstrated. The influences of organic and inorganic matrices, the laser energy, the laser wavelength, and the sample plate material on desorption of protein molecules from sample plates were discussed. In addition, the effects of the composition of the electrospray solution on the ionization of the desorbed protein molecules were studied. PMID- 20309449 TI - Rapid fingerprinting and classification of extra virgin olive oil by microjet sampling and extractive electrospray ionization mass spectrometry. AB - Microjet sampling in combination with extractive electrospray ionization (EESI) mass spectrometry (MS) was applied to the rapid characterization and classification of extra virgin olive oil (EVOO) without any sample pretreatment. When modifying the composition of the primary ESI spray solvent, mass spectra of an identical EVOO sample showed differences. This demonstrates the capability of this technique to extract molecules with varying polarities, hence generating rich molecular information of the EVOO. Moreover, with the aid of microjet sampling, compounds of different volatilities (e.g.E-2-hexenal, trans-trans-2,4 heptadienal, tyrosol and caffeic acid) could be sampled simultaneously. EVOO data was also compared with that of other edible oils. Principal Component Analysis (PCA) was performed to discriminate EVOO and EVOO adulterated with edible oils. Microjet sampling EESI-MS was found to be a simple, rapid (less than 2 min analysis time per sample) and powerful method to obtain MS fingerprints of EVOO without requiring any complicated sample pretreatment steps. PMID- 20309450 TI - Atmospheric pressure-thermal desorption (AP-TD)/electrospray ionization-mass spectrometry for the rapid analysis of Bacillus spores. AB - A technique is described where an atmospheric pressure-thermal desorption (AP-TD) device and electrospray ionization (ESI)-mass spectrometry (MS) are coupled and used for the rapid analysis of Bacillus subtilis spores in complex matrices. The resulting AP-TD/ESI-MS technique combines the generation of volatile compounds and/or pyrolysis products with soft-ionization MS detection. In the AP-TD/ESI-MS approach, an electrospray solvent plume was used as the ionization vehicle of thermally desorbed neutrals at atmospheric pressure prior to mass spectrometric analysis using a quadrupole ion trap mass spectrometer. The approach is quantitative with the volatile standard dimethyl methylphosphonate (DMMP) and with the use of an internal standard (diethyl methylphosphonate, DEMP). A linear response was obtained as tested in the 1-50 ppm range (R(2) = 0.991) with a standard error of the estimate of 0.193 (0.9% RSD, n = 5). Bacterial spores were detected by performing pyrolysis in situ methylation with the reagent tetramethylammonium hydroxide (TMAH) for the detection of the bacterial spore biomarker dipicolinic acid (DPA) as the dimethylated derivative (2Me-DPA). This approach allowed spore detection even in the presence of growth media in crude lyophilized samples. Repetitive analyses could be performed with a duty cycle of less than 5 min total analysis time (including sample loading, heating and data acquisition). This strategy proved successful over other direct ambient MS approaches like DESI-MS and AP-TD/ESI-MS without the in situ derivatization step to detect the dipicolinic acid biomarker from spores. A detection limit for the dimethylated DPA biomarker was estimated at 1 ppm (equivalent to 0.01 mug of DPA deposited in the thermal desorption tube), which corresponded to a calculated detection limit of 10(5) spores deposited or 0.1% by weight spore composition in solid samples (assuming a 1 mg sample size). The AP-TD/ESI source used in conjunction with the in situ methylation step allowed the differentiation of bacterial spores from other 'suspicious white powders' using a single stage for mass analysis and with minimum sample preparation, making this approach suitable for simple field-portable MS instrumentation and pattern recognition data analysis. PMID- 20309456 TI - Computational enzymology. AB - Molecular simulations and modelling are changing the science of enzymology. Calculations can provide detailed, atomic-level insight into the fundamental mechanisms of biological catalysts. Computational enzymology is a rapidly developing area, and is testing theories of catalysis, challenging 'textbook' mechanisms, and identifying novel catalytic mechanisms. Increasingly, modelling is contributing directly to experimental studies of enzyme-catalysed reactions. Potential practical applications include interpretation of experimental data, catalyst design and drug development. PMID- 20309457 TI - A pH-sensitive graphene oxide composite hydrogel. AB - Graphene oxide/poly(vinyl alcohol) (GO/PVA) composite hydrogel was prepared and utilized for selective drug release at physiological pH. PMID- 20309458 TI - Experimental visualization of covalent bonds and structural disorder in a gallium zinc oxynitride photocatalyst (Ga(1-x)Znx)(N(1-x)Ox): origin of visible light absorption. AB - We present the experimental visualization of covalent bonding, positional disorders and split anion sites in visible-light responsive photocatalyst (Ga(0.885)Zn(0.115))(N(0.885)O(0.115)). ZnO alloying into GaN reduces the band gap, leading to the visible-light response. DFT calculations indicated no significant difference in band gap between structural models with and without split sites. PMID- 20309459 TI - Improved dynamics and positional bias with a second generation palladium(II) complexed molecular shuttle. AB - A second generation palladium(II)-complexed molecular shuttle, featuring structural changes to the size and shape of the macrocycle, shows significantly increased rates of shuttling and improved co-conformational bias compared to the original system. PMID- 20309460 TI - Detection of mercury in fish organs with a two-photon fluorescent probe. AB - We report a two-photon fluorescent probe (AHg1) that can be excited by 780 nm femto-second pulses, shows high photostability and negligible toxicity, and can visualize the site of Hg(2+) accumulation, but can also estimate trace amounts of mercury ions in fresh fish organs by two-photon microscopy. PMID- 20309461 TI - Observation of the selective staining of chromosomal DNA in dividing cells using a luminescent terbium(III) complex. AB - The emission intensity of a monocationic Tb or Eu(III) complex of a bis(1 azaxanthone) ligand is enhanced in the presence of serum albumin; the lanthanide complex stains dividing cells, allowing visualisation of mitotic chromosomes. PMID- 20309462 TI - Water reduction by photoexcited silica and alumina. AB - Excess electrons in solvent are amongst the most fascinating chemical species, at the very edge between physics and chemistry. In this contribution, we report the use of silica and alumina photochemistry to create and stabilize aqueous solutions of electron. PMID- 20309463 TI - A simple, novel method for preparing an effective water oxidation catalyst. AB - A novel oxygen catalyst is prepared via the photodeposition of ruthenium(IV) oxide on a titania photocatalyst derived from a perruthenate precursor. PMID- 20309464 TI - A quantum dot-based ratiometric pH sensor. AB - A quantum dot-based ratiometric pH sensor that responds to the pH range 6-8 was developed using FITC (fluorescein isothiocyanate) conjugated CdSe/CdZnS nanocrystals. PMID- 20309465 TI - Iron/iron oxide nanoparticles: a versatile support for catalytic metals and their application in Suzuki-Miyaura cross-coupling reactions. AB - Iron/iron oxide core-shell nanoparticles (Fe@Fe(x)O(y)) are a versatile support for immobilizing catalytic metals. Fe@Fe(x)O(y) decorated with Pd (Fe@Fe(x)O(y)/Pd) exhibits high catalytic activity toward Suzuki-Miyaura cross coupling reactions in aqueous solution at room temperature in air. PMID- 20309466 TI - Organocatalytic asymmetric synthesis of polyfunctionalized 3-(cyclohexenylmethyl) indoles via a quadruple domino Friedel-Crafts-type/Michael/Michael/aldol condensation reaction. AB - A new organocatalytic quadruple domino Friedel-Crafts-type/Michael/Michael/aldol condensation reaction has been developed. In this one-pot multi-component process acrolein, various indoles and nitroalkenes are used as starting materials. The diphenylprolinol TMS-ether catalysis provides a straightforward and efficient entry to 3-(cyclohexenylmethyl)-indoles bearing three stereogenic centers in moderate to excellent yields (23-82%) and excellent stereoselectivities (dr = 91 : 9 to >95 : 5, ee = 94 to >99%). PMID- 20309467 TI - A flow-based synthesis of imatinib: the API of Gleevec. AB - A concise, flow-based synthesis of Imatinib, a compound used for the treatment of chronic myeloid leukaemia, is described whereby all steps are conducted in tubular flow coils or cartridges packed with reagents or scavengers to effect clean product formation. An in-line solvent switching procedure was developed enabling the procedure to be performed with limited manual handling of intermediates. PMID- 20309468 TI - Organometallic control at the nanoscale: a new, one-pot method to decorate a magnetic nanoparticle surface with noble metal atoms. AB - A novel cascade of reactions is designed to control in situ the deposition of noble metal islands (e.g. Rh) on top of nanoparticles of a 3d metal (e.g. Fe, Co). PMID- 20309469 TI - Phosphinopnictinophosphonium frameworks. AB - Reactions of the cyclic tetraphosphine (CyP)(4) with arsenium or stibenium cations (R(2)Pn(+), Pn = As, Sb and R = Cl, Ph) give salts of the new cationic frameworks [(CyP)(4)(AN)](+), [(CyP)(4)(SbCl(2))](+) and [{(CyP)(4)}(2)(Sb(2)Cl(2))](2+). The cations can be viewed as coordination complexes of a cyclophosphine ligand on a pnictenium cation, or a cyclo-2,3,4 triphosphino-1-pnictino-1-phosphonium cation, representing the first branched cyclic pnictogen framework, and examples of tertiary phosphonium centers with As P or Sb-P bonds. PMID- 20309470 TI - Room-temperature synthesis of MnO2.3H2O ultrathin nanostructures and their morphological transformation to well-dispersed nanorods. AB - MnO(2).3H(2)O ultrathin nanostructures with sizes of approximately 2-3 nm were synthesized at room temperature and transformation to well-dispersed nanorods was achieved after hydrothermal treatments. PMID- 20309471 TI - Direct multiple C-H bond arylation reaction of heteroarenes catalyzed by cationic palladium complex bearing 1,10-phenanthroline. AB - A cationic palladium complex bearing 1,10-phenanthroline ligand is found to catalyze direct C-H arylation reactions of heteroarenes with aryl iodides to give mono-, di-, or tri-arylated products selectively. PMID- 20309472 TI - The synthesis of chiral N-heterocyclic carbene-borane and -diorganoborane complexes and their use in the asymmetric reduction of ketones. AB - Chiral N-heterocyclic carbene-borane complexes have been synthesised, and have been shown to reduce ketones with Lewis acid promotion. Chiral N-heterocyclic carbene-borane and -diorganoborane complexes can reduce ketones with enantioselectivities up to 75% and 85% ee, respectively. PMID- 20309473 TI - Organic dye-sensitized TiO2 for the redox conversion of water pollutants under visible light. AB - Titania nanoparticles sensitized with metal-free organic dye exhibit high visible light activities for the redox conversion of water pollutants in a wider pH range in comparison with TiO(2) sensitized with ruthenium bipyridyl complexes. PMID- 20309474 TI - Unusual reactivity in organoaluminium and NHC chemistry: deprotonation of AlMe3 by an NHC moiety involving the formation of a sterically bulky NHC-AlMe3 Lewis adduct. AB - A sterically congested NHC-AlMe(3) Lewis adduct (NHC = 1,3-di-tert-butylimidazol 2-ylidene) was found to either isomerize to an "abnormal" NHC-AlMe(3) species or to be involved in the deprotonation of AlMe(3) to form the corresponding imidazolium species along with an AlMe(3)-stabilized methylene aluminium anion. PMID- 20309475 TI - Determination of absolute configuration of trimeric indole alkaloid, psychotrimine, by first asymmetric total synthesis. AB - The first asymmetric total synthesis of psychotrimine, a trimeric indole alkaloid, was accomplished via an asymmetric Ireland-Claisen rearrangement to construct a chiral quaternary carbon center, thereby establishing the absolute configuration of psychotrimine. PMID- 20309476 TI - Diastereoselective HOTf-catalyzed three-component one-pot 1,3-dipolar cycloaddition of alpha-diazo ester, nitrosobenzene and electron-deficient alkene. AB - A novel HOTf-catalyzed three-component one-pot cycloaddition of alpha-diazo ester, nitrosobenzene and electron deficient alkene has been developed. This catalysis is very simple to operate and tolerant to moisture/oxygen to afford the product with high to excellent diastereoselectivity in good to excellent yield, thus providing a useful and convenient method for the preparation of diverse functionalized isoxazolidines under very mild conditions. PMID- 20309477 TI - Reversible, solid state capture of carbon dioxide by hydroxylated amidines. AB - Hydroxylated amidine derivatives can capture, store, and release CO(2) reversibly in the solid state in a quantitative manner under clean and dry conditions at ambient temperature. PMID- 20309482 TI - Click chemistry: function follows form. PMID- 20309483 TI - Fluorogenic click reaction. AB - Fluorogenic Cu(I)-catalyzed alkyne-azide cycloaddition (CuAAC) reactions have emerged as a powerful tool for bioconjugation, materials science, organic synthesis and drug discovery. This review highlights the design of the recent development of fluorogenic CuAAC reactions as well as their applications. PMID- 20309484 TI - The application of CuAAC 'click' chemistry to catenane and rotaxane synthesis. AB - The copper(I)-catalysed azide-alkyne cycloaddition (the CuAAC 'click' reaction) is proving to be a powerful new tool for the construction of mechanically interlocked molecular-level architectures. The reaction is highly selective for the functional groups involved (terminal alkynes and azides) and the experimental conditions are mild and compatible with the weak and reversible intermolecular interactions generally used to template the assembly of interlocked structures. Since the CuAAC reaction was introduced as a means of making rotaxanes by an 'active template' mechanism in 2006, it has proven effective for the synthesis of numerous different types of rotaxanes, catenanes and molecular shuttles by passive as well as active template strategies. Mechanistic insights into the CuAAC reaction itself have been provided by unexpected results encountered during the preparation of rotaxanes. In this tutorial review we highlight the rapidly increasing utility and future potential of the CuAAC reaction in mechanically interlocked molecule synthesis. PMID- 20309485 TI - In situ click chemistry: probing the binding landscapes of biological molecules. AB - Combinatorial approaches to the discovery of new functional molecules are well established among chemists and biologists, inspired in large measure by the modular composition of many systems and molecules in Nature. Many approaches rely on the synthesis and testing of individual members of a candidate combinatorial library, but attention has also been paid to techniques that allow the target to self-assemble its own binding agents. These fragment-based methods, grouped under the general heading of target-guided synthesis (TGS), show great promise in lead discovery applications. In this tutorial review, we review the use of the 1,3 dipolar cycloaddition reaction of organic azides and alkynes in a kinetically controlled TGS approach, termed in situ click chemistry. The azide-alkyne reaction has several distinct advantages, most notably high chemoselectivity, very low background ligation rates, facile synthetic accessibility, and the stability and properties of the 1,2,3-triazole products. Examples of the discovery of potent inhibitors of acetylcholinesterases, carbonic anhydrase, HIV protease, and chitinase are described, as are methods for the templated assembly of agents that bind DNA and proteins. PMID- 20309486 TI - Click chemistry under non-classical reaction conditions. AB - First described almost a decade ago, "click" reactions such as the Cu(I) catalyzed azide-alkyne cycloaddition (CuAAC) are widely used today in organic and medicinal chemistry, in the polymer and material science field, and in chemical biology. While most click reactions can be performed at room temperature there are instances where some form of process intensification is required. In this tutorial review, aimed at the synthetic chemistry community, examples of click chemistry carried out under non-classical reaction conditions, such as for example applying microwave heating or continuous flow processing will be highlighted. PMID- 20309487 TI - Copper-catalyzed azide-alkyne cycloaddition (CuAAC) and beyond: new reactivity of copper(I) acetylides. AB - Copper-catalyzed azide-alkyne cycloaddition (CuAAC) is a widely utilized, reliable, and straightforward way for making covalent connections between building blocks containing various functional groups. It has been used in organic synthesis, medicinal chemistry, surface and polymer chemistry, and bioconjugation applications. Despite the apparent simplicity of the reaction, its mechanism involves multiple reversible steps involving coordination complexes of copper(I) acetylides of varying nuclearity. Understanding and controlling these equilibria is of paramount importance for channeling the reaction into the productive catalytic cycle. This tutorial review examines the history of the development of the CuAAC reaction, its key mechanistic aspects, and highlights the features that make it useful to practitioners in different fields of chemical science. PMID- 20309488 TI - Kinetic target-guided synthesis. AB - In the last decade, various target-guided synthesis (TGS) approaches have been developed in which a target protein is actively engaged in the assembly of its own bidentate ligand from a pool of smaller reactive fragments. Although TGS is relatively less explored, it demonstrates great promise to streamline drug discovery by combining screening and synthesis into a single step. Herein, we focus on the class of kinetic TGS approaches which utilize irreversible reactions to combine two reactive fragments into the inhibitory compound. These kinetic TGS applications have been successful due to the unique combination of the slow nature of the chemical reaction combining the two fragments into a single molecule and the use of reactive fragments displaying good affinities toward one of the binding sites. So far, kinetic TGS and especially in situ click chemistry, a kinetic TGS variant using the 1,3-dipolar cycloaddition of azides and alkynes, have led to the identification of highly potent inhibitors. This tutorial review focuses on kinetic TGS approaches aside from those employing the 1,3-dipolar cycloaddition of azides and alkynes, and discusses the features and advantages of these TGS approaches in detail. PMID- 20309489 TI - Tricks with clicks: modification of peptidomimetic oligomers via copper-catalyzed azide-alkyne [3 + 2] cycloaddition. AB - This tutorial review examines recent developments involving use of Copper catalyzed Azide-Alkyne [3 + 2] Cycloaddition (CuAAC) reactions in the synthesis, modification, and conformational control of peptidomimetic oligomers. CuAAC reactions have been used to address a variety of objectives including: (i) ligation of peptidomimetic oligomers; (ii) synthesis of ordered "foldamer" architectures; (iii) conjugation of ligands to peptidomimetic scaffolds; and (iv) macrocyclization of peptidomimetics using triazole linkages as conformational constraints. Variations in synthesis protocols, such as the use of different solvent systems, temperatures and copper species are evaluated herein to present a range of variables for the optimization of CuAAC reactions. The overall objectives of these studies are assessed to highlight the widespread applications of the products, which range from bioactive ligands to new materials. PMID- 20309490 TI - Marrying click chemistry with polymerization: expanding the scope of polymeric materials. AB - Click chemistry constitutes a class of reactions broadly characterized by efficiency, selectivity, and tolerance to a variety of solvents and functional groups. By far the most widely utilized of these efficient transformation reactions is the Cu(I)-catalyzed azide-alkyne cycloaddition. This reaction has been creatively employed to facilitate the preparation of complex macromolecules, such as multiblock copolymers, shell or core cross-linked micelles, and dendrimers. This critical review highlights the application of click chemistry, in particular the Cu(I)-catalyzed azide-alkyne cycloaddition, to the synthesis of a wide variety of new materials with possible uses as drug delivery agents, tissue engineering scaffolds, and dispersible nanomaterials (83 references). PMID- 20309491 TI - Thiol-click chemistry: a multifaceted toolbox for small molecule and polymer synthesis. AB - The merits of thiol-click chemistry and its potential for making new forays into chemical synthesis and materials applications are described. Since thiols react to high yields under benign conditions with a vast range of chemical species, their utility extends to a large number of applications in the chemical, biological, physical, materials and engineering fields. This critical review provides insight into emerging venues for application as well as new mechanistic understanding of this exceptional chemistry in its many forms (81 references). PMID- 20309492 TI - Click chemistry with DNA. AB - The advent of click chemistry has led to an influx of new ideas in the nucleic acids field. The copper catalysed alkyne-azide cycloaddition (CuAAC) reaction is the method of choice for DNA click chemistry due to its remarkable efficiency. It has been used to label oligonucleotides with fluorescent dyes, sugars, peptides and other reporter groups, to cyclise DNA, to synthesise DNA catenanes, to join oligonucleotides to PNA, and to produce analogues of DNA with modified nucleobases and backbones. In this critical review we describe some of the pioneering work that has been carried out in this area (78 references). PMID- 20309495 TI - Morpho-histological study of banana (Musa spp. cv. Grande Naine [AAA]) cell suspensions during cryopreservation and regeneration. AB - In this work, a morpho-histological study of banana (Musa spp. cv. Grande Naine [AAA]) embryogenic cell suspensions during cryopreservation and regeneration was performed. It was demonstrated that the regeneration process of somatic embryos originating from cryopreserved cell suspensions was different from that of control cell suspensions. Somatic embryos originating from cryopreserved cell suspensions had a unicellular origin. The regeneration process was modified not only by freezing in liquid nitrogen but also by the plasmolyzing effect of the 0.5 M sucrose solution employed during pretreatment. This result explained the high number of embryonic structures formed on M3 medium, compared with the control. Proembryos blocked at the globular stage could pursue their development when they were plated on new culture medium at a lower density after 30 days of culture on M3 medium. The unicellular origin of somatic embryos produced from cryopreserved cell suspensions offers the prospect of using cryopreservation to select non-chimeral transformed plants. PMID- 20309496 TI - Addition of ficoll and disaccharides to vitrification solutions improve in vitro viability of vitrified equine embryo. AB - The aim of the present study was to evaluate the in vitro viability of equine embryos vitrified in three different solutions. Day 6 and 6.5 embryos were measured and morphologically evaluated. Only grade 1 or 2 morulae and early blastocysts were vitrified. Eighteen embryos were distributed in Group 1: 40 percent ethylene glycol in PBS, Group: 2 and 3: 40 percent ethylene glycol, 18 percent Ficoll, 0.3M sucrose or 0.3M trehalose in PBS, respectively. The vitrified embryos were loaded individually into 0.25 ml straws, which were cooled and immersed in liquid nitrogen. After warming at 20 degree C for 20s, the embryos were expelled out into 0.5M sucrose in PBS and transferred to PBS solution. The embryonic diameter was measured again and morphology and viability were evaluated with Propidium iodide and Hoechst 33258 dyes. Embryos vitrified with sucrose (19.2 percent) and trehalose (26.7 percent ) showed the highest percentage of viable cells and morphological quality. PMID- 20309497 TI - Can thermal expansion differences between cryopreserved tissue and cryoprotective agents alone cause cracking? AB - One of the limiting factors in large-scale cryopreservation is the formation of fractures. The prevalence of cracking in cryopreserved bulky tissues is frequently associated with temperature gradients, which lead to non-uniform thermal contraction of the tissue. With new cryoprotectants available, it may be possible to reduce temperature gradients to much lower levels, in which case other contributions to mechanical stress development and cracking will become more significant. One potential contributor to such stress is the difference in thermal expansion between tissue and the cryoprotectant. The current study addresses the role of thermal expansion mismatch by drawing upon recently obtained experimental data and engineering models for the development of thermal stresses. This question is addressed for the case of cryopreservation via vitrification (glass formation), for which crystal formation is avoided, and tissues and solutions gradually transition from fluid-like to solid-like response, as the viscosity increases with decreasing temperature. PMID- 20309498 TI - Can vitrified zebrafish blastomeres be used to obtain germ-line chimaeras? AB - Blastomere cryopreservation plays an important role in maintaining the genetic diversity for valuable fish species. Recently, an original procedure for blastomere vitrification in zebrafish (Danio rerio) was developed in our lab. In the present work, blastomeres from the wild strain embryos, previously vitrified thawed by this procedure, were injected into embryos from the gold strain in order to assess their ability to colonise the germ-line of recipient embryos. The blastomere survival rate at thawing (higher than 90 percent) as well as the whole number of recovered blastomeres per donor embryo (around 20 percent), were in the ranges previously reported for this vitrification technique. Despite this, only 2 adult chimaeric specimens were finally obtained from a total of 47 injected embryos. Signals of chimaerism were not detected at any stage of development of the chimaeric embryos (somatic chimaerism) or in adulthood (somatic and germ-line chimaerism). In relation to this, difficulties during blastomere insertion are thought to be responsible for the poor results obtained, their aspects being discussed in detail in this work. More improvements to overcome such technical difficulties are needed and, until then, blastomere vitrification may only be of interest for germplasm cryobanking. PMID- 20309499 TI - Cryopreservation strategies for Cyathea australis (R. BR.) domin. AB - The influence of liquid nitrogen (LN) on the germination of C. australis spores and survival of gametophytes at various stages of development was investigated. Exposure to LN did not change the viability of mature spores (80 percent) but stimulated the germination of immature spores from 1.9 percent to 41 percent. Disinfection before cryopreservation contributed to loss of spore survival. However, some germination capacity was regained (48 percent) if the sterilized spores were enclosed in alginate capsules and subsequently exposed to osmotic desiccation and 5-hour air drying. Development of gametophytes derived from frozen and non-frozen spores was similar. Preculture factors (the period, type and abscisic acid treatment) affected gametophyte viability and growth. A two week preculture on agar significantly increased survival compared to preculture in a liquid medium. Addition of abscisic acid (ABA) to solid or liquid media stimulated explant survival. Highest viability (85 percent) of frozen-thawed gametophytes was achieved by a 2-week preculture in agar with 0.25 M sucrose and 10 muM ABA. Gametophytes developed directly from spores grew and multiplied in vitro at a uniform rate. Young, intensively growing gametophytes and large, proliferating ones survived better (73-80 percent) following cryoexposure than mature, non proliferating gametophytes (50 percent). Less than one quarter of the explant surface was alive in 60-80 percent of the gametophytes that survived cryoexposure. PMID- 20309500 TI - Cryopreservation of embryogenic cultures of Dioscorea bulbifera l. by encapsulation- dehydration. AB - Embryogenic cultures of Dioscorea bulbifera were cryopreserved using an encapsulation- dehydration procedure with subsequent plant regeneration. Embryogenesis was induced by culturing in vitro grown axillary bud meristems on MS medium supplemented with 2.0 mg per liter 2,4-D. After cryopreservation, recovery growth of embryogenic culture up to 53.3 percent was recorded when excised proliferating embryogenic cultures of 1.5-2.0 mm in diameter were: encapsulated in 3 percent calcium alginate containing 0.15 M sucrose followed by preculturing with 0.5 M sucrose for 3 d; dehydrated in the laminar air flow for 4 h, thereby reducing the bead moisture content to 19.4 percent ( fresh weight basis); plunged into liquid nitrogen; thawed at 40 degree C; and cultured on recovery growth medium, i.e. MS supplemented with 2.0 mg per liter 2,4-D and 0.3 mg per liter BAP. However, preculturing for an extended period of 7 d increased the recovery growth further to 67.8 percent. During recovery growth the embryogenic tissue protruded out of the beads without loss of structural integrity of the cryopreserved embryos. Subculturing of these cultures on to embryo conversion medium, i.e. MS medium with 0.5 mg per liter zeatin and 400 mg per liter glutamine, resulted in production of plantlets through embryo conversion. The regenerated plantlets exhibited the same morphology as that of originally maintained in vitro plantlets and were established in vivo, in a net house with 80 percent success. PMID- 20309501 TI - Cryobanking of human ovarian tissue for anti-cancer treatment: comparison of vitrification and conventional freezing. AB - The first case of cryopreservation of human ovarian tissue with good survival of follicles after warming was described in 1996. Childbirth after cryopreservation of ovarian tissue is now a reality. Cryopreservation of ovarian tissue can be performed using one of two methods: conventional ("slow") freezing and cryopreservation by direct plunging into liquid nitrogen (so called vitrification or "rapid" freezing). Comparative investigations of vitrification and conventional freezing performed on mammalian ovarian tissue are limited, and authors present different conclusions. The higher effectiveness of vitrification in comparison with conventional freezing for human oocytes and embryos was shown, whereas data on human ovarian tissue are limited. The aim of different studies was to compare the safety and effectiveness of conventional freezing and vitrification of human ovarian tissue. Below we shortly summarize the results of some investigations with different conclusions. The discussion on the post warming quality of follicles as well as on the problems of microbial contamination of cells in liquid nitrogen at vitrification is presented. In our opinion, for cryopreservation of human ovarian tissue, conventional freezing is more promising than vitrification. PMID- 20309502 TI - Effect of the size of zona pellucida thinning by laser assisted hatching on clinical outcome of human frozen-thawed embryo transfers. AB - Of 122 consecutive procedures, 31 were not assisted hatching (AH), which served as the control group, 34 were AH with 40 microm thinning of the zona, and 57 were AH with 80 microns of the zona thinning. The pregnancy and implantation rates were significantly higher in 80 microns thinning group compared to control group (40.3 vs. 16.1 percent, P=0.03; 21.5 vs. 7.5 percent, P=0.007, respectively). In addition, the implantation rate was signigicantly higher in 80 microns group than in 40 microns group (21.5 percent vs.9.4 percent, P=0.024). The results indicated that the size of the zona pellucida thinning by laser may influence the pregnancy and implantation rates following frozen-thawed cleaved embryo transfer. PMID- 20309503 TI - Overcoming recalcitrance in Porphyridium aerugineum Geitler employing encapsulation-dehydration cryopreservation methods. AB - Cultures of the recalcitrant microalga Porphyridium aerugineum were cryopreserved. A two-step, uncontrolled rapid freezing protocol, using methanol as cryoprotectant resulted in 23.8 percent viable cells. Cultures in the exponential growth phase, grown under low light intensity to prevent vacuole formation in cells, cryopreserved using a passive freezer, showed 22.4 percent viability. This value was enhanced to 31.5 percent when a controlled-rate freezer was employed. Optimized cultures in the exponential growth phase, cultivated in medium supplemented or not with vitamin B12, were then tested for freezing using the encapsulation-dehydration protocol. High cell loss was observed early during the sorbitol dehydration steps, but 63.6 percent of the remaining encapsulated cells were viable after thawing. This study confirmed the potential of encapsulation-dehydration as a method allowing to improve the low viability obtained with two-step freezing protocols. It also showed the importance of monitoring the response of algal cells to bead osmotic and evaporative dehydration pretreatments before freezing. PMID- 20309504 TI - Detection of 8-hydroxy-2-deoxyguanosine as a marker of oxidative damage in DNA and germplasm exposed to cryogenic treatments. AB - An HPLC method has been optimised to measure 8-hydroxy-2-deoxyguanosine (8OHdG) in DNA and germplasm with the objective of using the adduct as a marker of cryostorage stability. The encapsulation-dehydration cryopreservation protocol was adapted as a model system for assessing the formation of 8OHdG from alginate encapsulated DNA of calf thymus (CT) and currant species (Ribes) exposed to temperatures of -20 and -196 degree C. The presence of H2O2 exacerbated the formation of 8OHdG in encapsulated CT and Ribes DNA. Production of the oxidized adduct was lower in the plant system. A reduction in residual water following osmotic dehydration and evaporative desiccation was associated with reduced adduct formation in encapsulated DNA. No significant differences in 8OHdG adduct formation were observed in plants regenerated from cryopreserved Ribes meristems derived from genotypes known to have differential tolerance to cryopreservation. PMID- 20309505 TI - Cryopreservation of Thymus moroderi by droplet vitrification. AB - Thymus moroderi Pau ex Martinez (Labiatae) was successfully cryopreserved using the droplet vitrification method. After 20 min in loading solution at room temperature, shoot tips were dehydrated with PVS2 at 0 degree C for 30 min and immersed into LN. For thawing, shoot-tips were transferred into recovery solution for 15 min. A test of different recovery media revealed that the best results were obtained when the medium was supplement with 0.275 micromolar BA. PMID- 20309506 TI - Vitrification of mosses: a useful method for the cryopreservation of Splachnum ampullaceum Hedw. AB - The source of germplasm as well as the technique used for storage of mosses can enhance survival after cryopreservation. Samples of gametophores, protonemata and protonemal brood cells from in vitro cultures of Splachnum ampullaceum were cryopreserved following exposure to a plant vitrification solution (PVS2) for two different times (5 and 10 min) at 0 degree C. Half of the samples were pretreated with a loading solution containing 2 M glycerol and 0.4 M sucrose before exposure to PVS2. After one week storage in liquid nitrogen, S. ampullaceum samples were regenerated on Gamborg's B5 mineral medium with B5 vitamins. Exposure to a loading solution was a prerequisite for high survival in all samples. Four weeks after cryopreservation, 92.3 percent brood cells, 60.0 percent gametophores and 46.0 percent protonemata pretreated with a loading solution had regenerated, displaying normal growth and development, thus demonstrating that vitrification is a useful method for moss cryopreservation. PMID- 20309507 TI - Critical moisture content windows differ for the cryopreservation of pomelo (Citrus grandis) seeds and embryonic axes. AB - Cryopreservation was attempted using a partial dehydration and freezing protocol on pomelo (Citrus grandis) seeds of ten cultivars and embryonic axes of one cultivar collected from Xishuangbanna. Although seeds of all ten cultivars could be dehydrated safely to 10 percent moisture content, further dehydration impaired seed viability with critical moisture contents ranging from 9 percent to 7 percent. Complete seedling regenerated from seeds frozen in a moisture window between 5-9 percent, and maximum seedling recovery varied between 22-86 percent. Cryopreservation of Jiajieyou cv. embryonic axes had a moisture window between 3 20 percent , much wider compared to whole seed cryopreservation, and maximum post thaw emergence of 93 percent was achieved at 13 percent moisture content. Emergence differed only slightly from survival when whole seeds were cryopreserved, but for the embryonic axis cryopreservation at low moisture contents resulted in much lower emergence than survival. Possible causes of intraspecific variation in cryotolerance in pomelo seeds is discussed. PMID- 20309508 TI - Cryopreservation of Fraser photinia (Photinia x fraseri Dress.) via vitrification based one-step freezing techniques. AB - An efficient vitrification-based cryopreservation procedure was developed for Fraser photinia shoot apices by assessing the influences of various vitrification solutions (PVS1, PVS2, PVS3 and VSL) and different vitrification methods (cryovial vitrification, droplet vitrification and droplet freezing) on shoot regrowth. Moreover, influences of cold-hardening period (0 to 8 weeks), preculture medium (with sucrose and proline) and regrowth medium (QL plus 4.4, 8.8 and 17.6 micromolar BA) were also evaluated. Among the different procedures tested, best shoot regrowth (40.3 percent) was achieved by using a droplet vitrification technique in which cold-hardened and precultured shoot apices were vitrified for 120 min at 0 degree C in droplets, rapidly cooled, thawed and then cultured on 17.6 micromolar BA-containing QL medium. Overall results indicated the importance of not only the composition of vitrification solution, and preculture and regrowth media, but also the application of an appropriate vitrification technique to achieve optimum recovery post-cryopreservation. PMID- 20309509 TI - Effect of timing, dose and interstitial versus nanoparticle delivery of tumor necrosis factor alpha in combinatorial adjuvant cryosurgery treatment of ELT-3 uterine fibroid tumor. AB - Cryosurgery has shown potential as a minimally invasive technology for tumor treatment. However, incomplete destruction followed by tumor recurrence after cryosurgery is a common drawback. This study characterizes several variables in the cryoadjuvant TNF-alpha enhancement of conservative cryosurgery (i.e. freezing to the visible edge) of ELT-3 (uterine leiomyoma) tumor in a female nude mouse model. The variables include pretreatment time, mode of TNF-alpha delivery (native vs. CYT-6091, a PEGylated 33 nm colloidal gold core nanoparticle) and dose of TNF-alpha. Survival and tumor growth delay were measured up to 30 days and showed: 1) pretreatment with TNF-alpha required 4 hours incubation prior to cryosurgery to produce a tumor growth delay over cryosurgery alone, and 2) CYT 6091 reduced the toxicity of TNF-alpha administration over intratumoral or peritumoral injection of native TNF-alpha. Taken together, 5 microgram TNF-alpha delivered by the nanodrug CYT-6091 4 hours prior to cryosurgery yielded a dramatic reduction in tumor growth over cryosurgery alone and in some cases even total remission of the tumor. However, some toxicity at higher doses (i.e. 5 micrograms) with CYT-6091 was noted compared to previous work in prostate (LNCaP) cancer grown in a male nude mouse. Potential reasons for this, including sex and weight of the animals are discussed. Further opportunities to optimize the TNF alpha enhanced cryosurgical response of this tumor include dosing between 2 - 5 microgram at 4 hours prior to cryosurgery, and freezing beyond the visible edge of the tumor. PMID- 20309510 TI - Cryopreservation of Fraxinus excelsior L. embryogenic callus by one-step freezing and slow cooling techniques. AB - An efficient cryopreservation protocol for the safe storage of Fraxinus excelsior L. embryogenic callus cultures is reported. The cryopreservation methods tested included one-step freezing by means of (i) encapsulation-vitrification; or (ii) encapsulation-dehydration; and (iii) slow cooling using the Nalgene Freezing container, Mr Frosty, which produces a temperature decrease of about 1 masculineC min-1 when placed in a -70 degree C freezer. None of the one-step freezing techniques was effective for cryopreservation of encapsulated callus masses, irrespective of the cryoprotective treatment applied, i.e., treatment with the PVS2 vitrification solution or physical dehydration with silica gel before direct immersion in liquid nitrogen. On the contrary, when a slow cooling protocol was applied to embryogenic callus which had been pretreated for 60 min with a 210 g per liter (0.61 M) sucrose-7.5 percent DMSO cryoprotective solution, up to about 1.3 g per Petri dish of proliferating callus was observed 42 days after recovery from liquid nitrogen, and cultures were able to produce somatic embryos 8 weeks after transfer to semi-solid medium. TTC staining of callus cultures provided a fast evaluation of culture viability. PMID- 20309511 TI - [Targeted therapy of basal cell carcinoma through inhibition of the hedgehog signaling pathway]. PMID- 20309512 TI - [A rare case of a sclerodermoid chronic graft versus host disease. Successful treatment with extracorporeal photopheresis (ECP)]. AB - A 31-year-old woman presented with progressive deep linear induration on her lower abdomen, forearms and thighs. These symptoms developed three years after allogenic stem cell transplantation. Furthermore, the patient showed multiple hypopigmented lichenoid papules on the extensor surfaces of the forearms consistent with lichen sclerosus. Histological analysis of a biopsy specimen from her left thigh showed dermal sclerosis extending into the fascia, thus establishing the diagnosis of a rare combination of superficial and deep sclerodermoid chronic graft-versus-host disease. After 7 cycles of extracorporeal photopheresis, a marked resolution of the indurations and a reduction of the modified Rodnan skin score from 12 to 7 were noted. PMID- 20309513 TI - [Rehabilitation for occupational dermatoses. Outpatient and inpatient measures]. AB - In recent years, the number of reports of suspicions of occupational diseases, received by the public statutory employer's liability insurance bodies, has remained constant. The recognition of occupational diseases under number 5101 BKV, however, has decreased considerably. This is more than likely due to improved prevention management concepts by the public statutory employer's liability insurance bodies. Nevertheless there are still severe occupational skin diseases that are resistant to or relapse under therapy, thus threatening discontinuation of the occupation. For these cases, an interdisciplinary inpatient treatment as a tertiary individual prevention measure was introduced. This consists of a three-week inpatient period followed by a three-week outpatient sick leave for further stabilization of the skin condition. During the inpatient stay intensive dermatological diagnosis and treatment are accompanied by in-depth health education seminars and psychological interventions. The selection of individually suitable skin protection measures and their practical trial in a workplace simulation model with an ergotherapist are of particular importance. Evaluations of this program showed that two-thirds of the participants with the defined risk of having to give up their occupation were able to continue with their occupation on a long-term basis. PMID- 20309514 TI - [Dermatologic-psychosomatic rehabilitation]. AB - Dermatologic-psychosomatic rehabilitation is indicated when a patient has both cutaneous and psychological disease, as well as when psychosocial factors have a negative influence on the course of disease or coping mechanisms. The goals of multimodal dermatologic and psychotherapeutic treatment are increased empowerment and self-action, as well as acceptance of disability. Requirements for admission are given with regard to ICF. The course of rehabilitation is explained and the most important therapeutic tools are presented. PMID- 20309515 TI - [Holistic approach to in-patient dermatological rehabilitation]. AB - Chronic diseases usually limit patients severely in their working, social and family life. With many chronic or chronically recurring skin diseases, particularly atopic disorders, it is often impossible to define specific causes that will respond to treatment. Since a full cure cannot be achieved in constitutional dermatoses, a holistic therapeutic approach is required. This must go beyond the identification, treatment and cure of the disease, and take into account the reciprocal interactions between the patient's organic, emotional and social symptoms. Based on the bio-psycho-social model of disease and health, modern dermatological rehabilitation therefore applies a holistic concept which goes well beyond dermatological treatment, also including the dimensions of function, activity, participation and context. The holistic approach is based on findings in rehabilitation science and takes into account the principles of complexity, interdisciplinary care and individuality. PMID- 20309516 TI - [Biomechanical principles for treatment of osteoporotic fractures of the pelvis]. AB - Fractures of the pelvis are of increasing interest, especially in older patients due to the often concomitant osteoporosis. The low bone quality can be a problem in several fixation situations. In this review the present and relevant literature on biomechanical data of unstable pelvic ring injuries and all biomechanical data dealing with osteosynthesis for acetabular fractures are discussed. PMID- 20309517 TI - Does egg colouration reflect male condition in birds? AB - How colouration provides information about individuals in birds has been a central issue in recent decades. Although much information has been derived, little is known about the adaptive significance of egg colouration in birds. A recent idea suggests that biliverdin- and porphyrin-pigmented eggs may act as a post-mating sexual signal for males to assess female quality. In birds, it is common for males to influence prelaying female condition by courtship feeding. Using Eurasian kestrels, a species that lays protoporphyrin-pigmented eggs, we descriptively assessed the influence of male feeding on egg pigmentation by considering female phenotype, condition, breeding parameters and male body condition. We found that older females and females with greyer tails (an index of individual quality) produce highly pigmented eggs. However, male body condition was the only variable that explained egg colouration when considered together with the female-related variables. Therefore, females that mated with males in better condition laid highly pigmented eggs. With the same species, we also explored the cost of producing protoporphyrin-pigmented eggs using a food-supply experiment before the laying period. Food supplementation did not increase egg pigmentation, but hatching success and egg mass were positively related to egg colouration only in food supplied pairs. We suggest that egg colouration might be costly to produce and probably suggests egg quality. However, this cost cannot be explained by female quality, but by male condition instead. In general, our results do not support the theory that egg colouration is a post-mating sexual signal in species where males determine female condition at the time of laying. PMID- 20309518 TI - [Pitfalls and difficulties in interpretation of bone densitometry]. AB - The clinical relevance of osteoporosis as a frequent systemic skeletal disease is to be found in fractures and their consequences. For prevention of these disease manifestations great importance must be attached to a safest possible diagnosis even before the occurrence of the first fracture and osteodensitometry is a well established technique for this purpose. Among the different measurement procedures DXA (dual-energy X-ray absorptiometry) has become the gold standard worldwide. This method is seen as very reliable and adequately precise. Prerequisites for these characteristics are the correct interpretation of the measurement data obtained by taking into consideration all potential influencing factors which can either false positively or false negatively influence a single value as well as the calculated mean value and the T and Z scores. Thus, exact knowledge of potential sources of error is of crucial importance. The present study shows important sources of error and difficulties in interpretation as well as a discussion of the options for their prevention. For the clinical practice osteodensitometry is to be seen as an important diagnostic component, which can only been interpreted meaningfully with respect to the clinical data. PMID- 20309519 TI - [Medical training therapy with special consideration to osteoporosis of the spinal column]. AB - Medical training therapy (MTT) plays a decisive role in maintenance and development of musculoskeletal health of humans in all phases of life. In childhood and adolescence it can contribute to the highest possible so-called peak bone mass and thus avoid or delay the appearance of osteoporosis for as long as possible, in view of increased life expectations. In young adults targeted MTT is well suited to improve performance and to maintain the maximum developed bone mass. The latter is also true for perimenopausal and postmenopausal women in whom MTT can compensate for the loss of bone mass due to hormone deficiency in comparison to those not in training. Elderly people who have possibly already suffered several fractures and who are in danger of becoming permanently dependent on external help due to increasing fragility can still improve muscle strength and mass by regular MTT even in advanced age. This will reduce or avoid the risk of falling and maintain the ability to be self-sufficient for as long as possible. In order to support this, rehabilitation measures even in-hospital, could be useful and should be especially promoted in line with the amendments to the social legislation effective from 1st April 2007 ("Rehabilitation before nursing"). PMID- 20309520 TI - Pneumonia associated with invasive and noninvasive ventilation: an analysis of the German nosocomial infection surveillance system database. AB - PURPOSE: Pneumonia associated with invasive mechanical ventilation (IMV) is one of the indicator infections of the German Nosocomial Infection Surveillance System. In 2005 surveillance was extended to include pneumonia associated with noninvasive ventilation (NIV). The aim of this study was to determine the utilization of IMV and NIV and the associated incidence densities (IDs) of pneumonia and to compare the characteristics of pneumonia cases and the spectrum of associated pathogens. METHODS: We analyzed the pooled data of 400 intensive care units (ICUs) with respect to three categories of pneumonia: pneumonia associated with IMV and NIV and pneumonia not associated with ventilation. Pooled ventilation utilization rates and pneumonia IDs were calculated in total and stratified by hospital size, hospital type and ICU type. RESULTS: Four hundred ICUs with 779,500 admitted patients, 1,068,472 IMV days and 101,569 NIV days reported 6,869 cases of pneumonia between 2005 and 2007. Of these, 5,811 cases were associated with IMV, 160 with NIV and 898 were not associated with ventilation. The mean pneumonia IDs were 1.58 and 5.44 cases per 1,000 ventilator days for NIV and IMV, respectively. Pneumonia cases associated with IMV were younger, had a longer ICU stay before onset of pneumonia and were more often associated with gram-negative bacteria than cases associated with NIV; however, there were no differences in the proportion of secondary sepsis and death. CONCLUSIONS: This surveillance study including pneumonia associated with IMV and NIV and pneumonia not associated with ventilation shows significant differences of pneumonia IDs, patient characteristics and the spectrum of associated pathogens. PMID- 20309521 TI - Septic shock due to Legionella pneumophila serogroup 2: usefulness of molecular biology for diagnosis, treatment and epidemiological investigation. PMID- 20309522 TI - Anatomy of the ankle ligaments: a pictorial essay. AB - Understanding the anatomy of the ankle ligaments is important for correct diagnosis and treatment. Ankle ligament injury is the most frequent cause of acute ankle pain. Chronic ankle pain often finds its cause in laxity of one of the ankle ligaments. In this pictorial essay, the ligaments around the ankle are grouped, depending on their anatomic orientation, and each of the ankle ligaments is discussed in detail. PMID- 20309523 TI - Adrenal effects of teriparatide in the treatment of severe postmenopausal osteoporosis. AB - The aim of our study was to investigate the effects of teriparatide on the hypophysis-adrenal axis in postmenopausal women. Treatment with teriparatide increased plasmatic and urinary levels of cortisol after 6 and 12 months. Our paper demonstrates a possible direct secretagogue effect of teriparatide on adrenals in osteoporotic postmenopausal women. INTRODUCTION: Teriparatide, recombinant human parathyroid hormone (1-34) (rhPTH [1-34]), is approved for the treatment of osteoporosis in men and postmenopausal women at high risk for fracture. In literature, data regarding the secretagogue effect of PTH on adrenocortical cells are present on in vitro, but not on in vivo, studies. The aim of our study was to investigate the effects of teriparatide on the hypophysis adrenal axis in postmenopausal women. METHODS: Twenty postmenopausal women with severe osteoporosis were treated with teriparatide in a regimen of 20 MUg daily, self-administered injections at bedtime for 12 months and a calcium and vitamin D supplementation. At the same time, 20 osteopenic women matched for age and body mass index with the patients were enrolled and treated only with calcium and vitamin D. In all subjects, calcium, adrenocorticotropic hormone (ACTH), and plasmatic and urinary cortisol were evaluated at baseline and after 6 and 12 months. RESULTS: Treatment with teriparatide increased plasmatic and urinary levels of cortisol after 6 and 12 months, reaching statistical significance only after 1 year. Plasmatic levels of ACTH did not change significantly. CONCLUSIONS: Our paper, for the first time, demonstrates a possible direct secretagogue effect of teriparatide on adrenals in osteoporotic postmenopausal women. PMID- 20309524 TI - What is the best balance of benefits and risks among anti-resorptive therapies for postmenopausal osteoporosis? AB - Pharmacologic osteoporosis therapy, particularly anti-resorptives, is recommended in postmenopausal women with clinical risk factors for fracture. Treatment decisions should be made based on the relative benefit-risk profile in different patient populations. Emerging options [e.g., selective estrogen receptor modulators (SERMs) and denosumab] may hold promise for providing protection from bone loss and for fracture risk reduction.Osteoporosis, the most common clinical disorder of bone metabolism, is characterized by low bone mineral density, deterioration of microarchitecture, and a consequent increase in bone fragility and risk of fracture. Pharmacologic therapy is recommended in postmenopausal women with clinical risk factors for fracture and includes anti-resorptive agents such as bisphosphonates, hormone therapy, SERMs, and calcitonin. The anabolic agent teriparatide (parathyroid hormone) is usually reserved for high-risk patients or those with glucocorticoid-induced osteoporosis. Strontium ranelate, available outside the USA, has both anti-resorptive and anabolic properties. Supplementation with calcium and vitamin D is recommended for all women aged 50 years and older. Bisphosphonates are often considered first-line therapy for osteoporosis and have the largest base of clinical trial data showing efficacy for global fracture risk reduction. Low-dose hormone therapy is appropriate for younger women who are experiencing other menopausal symptoms. In women for whom bisphosphonates are not appropriate or not tolerated or in younger postmenopausal women who have a low risk for hip fracture, SERMs are a suitable treatment option. Calcitonin is designated for patients who are unable or unwilling to tolerate other osteoporosis agents. Emerging options, including newer SERMs (e.g., bazedoxifene and lasofoxifene) and the monoclonal antibody denosumab, may hold promise for providing protection from bone loss and for fracture risk reduction. Because no single agent is appropriate for all patients, treatment decisions should be made on an individual basis, taking into account the relative benefits and risks in different patient populations. PMID- 20309525 TI - The Ontario Osteoporosis Strategy: implementation of a population-based osteoporosis action plan in Canada. AB - In the last decade, there have been a number of action plans published to highlight the importance of preventing osteoporosis and related fractures. In the province of Ontario Canada, the Ministry of Health provided funding for the Ontario Osteoporosis Strategy. The goal is to reduce morbidity, mortality, and costs from osteoporosis and related fractures through an integrated and comprehensive approach aimed at health promotion and disease management. This paper describes the components of the Ontario Osteoporosis Strategy and progress on implementation efforts as of March 2009. There are five main components: health promotion; bone mineral density testing, access, and quality; postfracture care; professional education; and research and evaluation. Responsibility for implementation of the initiatives within the components is shared across a number of professional and patient organizations and academic teaching hospitals with osteoporosis researchers. The lessons learned from each phase of the development, implementation, and evaluation of the Ontario Osteoporosis Strategy provides a tremendous opportunity to inform other jurisdictions embarking on implementing similar large-scale bone health initiatives. PMID- 20309526 TI - Age, cohort and period effects on hip fracture incidence: analysis and predictions from New Zealand data 1974-2007. AB - Hip fractures are substantial problem worldwide. The increase in rate with age does not continue into very old age. Rates decline in successive birth cohorts. If the increasing trend in period effect continues, there will be a substantial increase in hip fracture incidence. INTRODUCTION: The purpose of this study is to (1) determine incidence rates for fracture neck of femur (FNF) for the period 1974-2007, (2) estimate age, cohort, and period effects, and (3) predict the burden of FNF in 2025. METHODS: Age adjusted incidence rates were estimated using New Zealand hospital discharge data for 1974-2007. Age-period-cohort modeling was used to estimate individual effects of these factors after adjusting for the other two factors. Future fracture burden was estimated under two scenarios. RESULTS: Age-adjusted rates for women increased from 1974 to 1987 whereas rates for men have increased from 1974 until 2007. Risk increased from 70 years of age but dropped among the very elderly. Period effects showed a steady increase in risk throughout 1974-2007. In contrast, the risk was lower in later cohorts. If there is no change in the period effect from 2007 we estimate a reduction in the burden of illness from FNF, especially for women. However if the period effect continues to increase, there will be substantial increases in FNF incidence, especially for men. CONCLUSIONS: The effect of population aging on FNF incidence is predictable because projections are based on an existing population. The increasing health and improvement in measures of physical status of older people through the last century, explain the decline in FNF incidence in later cohorts. The steady increase in period effect may be due to increased survival of the very frail. This burden of illness resulting from FNFs must be addressed by population based, research proven approaches to fall and fracture prevention. PMID- 20309527 TI - Femoral neck bone mineral density in ambulatory men with poliomyelitis. AB - We evaluated bilateral femoral neck bone mineral densities (FNBMDs) in 32 men with poliomyelitis and their matched controls. Men with poliomyelitis had significantly lower FNBMD in both legs, and FNBMD was lowest in their shorter legs. Knee extensor strength and regular exercise were important predictive factors associated with decreased FNBMD. INTRODUCTION: People with poliomyelitis (polio) are prone to leg fractures after mild trauma. The flaccid paralysis, asymmetric involvement, and underdeveloped growth of afflicted legs may lead to osteoporosis of either leg, characterized by different patterns. This study aimed to measure their femoral FNBMD and to explore the factors associated with changes in FNBMD in either leg. METHODS: We did a prospective study to evaluate bilateral FNBMD with dual-energy X-ray absorptiometry in 32 men with polio (age range, 41 57 years; mean, 47 years) and 32 age- and body mass index-matched controls. Measuring the difference in leg length, we classified the legs of each polio subject as "longer" or "shorter." In addition, we chose the right leg of each control as a reference leg. We then used the Mann-Whitney U test to compare FNBMD of these three groups of legs and searched for the factors associated with FNBMD using stepwise multiple regression analyses. RESULTS: Compared to the reference leg, men with polio had significantly lower FNBMD in both their longer and shorter legs, by 13% and 23%, respectively. The difference in FNBMD between the two legs of polio subjects was significant. Knee extensor strength and regular exercise were two important factors associated with bilateral FNBMD in men with polio. CONCLUSIONS: Men with polio had lower bilateral FNBMD. FNBMD of the shorter leg should be the choice for predicting the risk of hip fracture in men with polio because on average, the shorter leg has lower BMD. PMID- 20309528 TI - Norepinephrine transporter occupancy by antidepressant in human brain using positron emission tomography with (S,S)-[18F]FMeNER-D2. AB - RATIONALE: Central norepinephrine transporter (NET) is one of the main targets of antidepressants. Although the measurement of NET occupancy has been attempted in humans, the outcomes have been inconclusive. OBJECTIVE: In this study, the occupancy of NET by different doses of an antidepressant, nortriptyline, was measured using positron emission tomography (PET) with (S,S)-[(18)F]FMeNER-D(2). MATERIALS AND METHODS: PET scans using (S,S)-[(18)F]FMeNER-D(2) were performed on six healthy men before and after oral administration of a single oral dose of nortriptyline (10-75 mg). After a bolus i.v. injection of (S,S)-[(18)F]FMeNER D(2), dynamic scanning was performed for 0-90 min, followed by scanning for 120 180 min. The ratio of the thalamus-to-caudate areas under the curve (120-180 min) minus 1 was used as the binding potential (BP(ND)) for NET. NET occupancy was calculated as the percentage reduction of BP(ND). Venous blood samples were taken to measure the concentrations of nortriptyline just before injection of the tracer and at 180 min after the injection. RESULTS: Mean NET occupancies by nortriptyline were 16.4% at 10 mg, 33.2% at 25 mg, and 41.1% at 75 mg. The mean plasma concentration of nortriptyline was less than the lower limit of detection at 10 mg, 23.7 ng/mL at 25 mg, and 50.5 ng/mL at 75 mg. Estimated ED(50) was 76.8 mg of administration dose and 59.8 ng/mL of plasma concentration. CONCLUSIONS: NET occupancy by nortriptyline corresponding to the administration dose of 10-75 mg or plasma concentration was observed from 16% to 41%. PMID- 20309529 TI - Reinstatement of extinguished amphetamine self-administration by 3,4 methylenedioxymethamphetamine (MDMA) and its enantiomers in rhesus monkeys. AB - RATIONALE: The effectiveness of MDMA and its enantiomers to reinstate responding previously maintained by drug self-administration has not been thoroughly investigated. OBJECTIVES: The present study was designed to compare the reinstatement effects of amphetamine, the piperazine-analog BZP, SR(+/-)-MDMA, S(+)-MDMA, R(-)-MDMA, and fenfluramine on behavior maintained under a second order schedule of intravenous amphetamine self-administration in rhesus monkeys (n=4). METHODS: Following saline substitution and extinction, a range of doses of amphetamine, BZP, SR(+/-)-MDMA, S(+)-MDMA, R(-)-MDMA, and fenfluramine were administered i.v. as non-contingent priming injections in order to characterize their effectiveness to reinstate responding previously maintained by amphetamine self-administration. RESULTS: Priming injections of amphetamine, BZP, SR(+/-) MDMA, and S(+)-MDMA induced significant reinstatement effects. In contrast, neither R(-)-MDMA nor fenfluramine effectively reinstated behavior. Pretreatment with the selective serotonin transporter inhibitor, fluoxetine, attenuated the reinstatement effects of SR(+/-)-MDMA, S(+)-MDMA, and BZP but had no significant effect on amphetamine-primed reinstatement. CONCLUSIONS: Given the profile of neurochemical effects published previously, these findings suggest that the reinstatement effects of MDMA are mediated primarily by dopamine release; however, the attenuation of MDMA-induced reinstatement by fluoxetine supports previous research demonstrating the complex behavioral pharmacology of MDMA-like drugs and that the reinstatement effects of MDMA are at least partially mediated by serotonergic mechanisms. PMID- 20309530 TI - Rapid development of tolerance to sub-anaesthetic dose of ketamine: an oculomotor study in macaque monkeys. AB - BACKGROUND: Ketamine, a non-competitive N-methyl-D: -aspartic acid antagonist, has been widely used for anaesthetic purposes. At sub-anaesthetic dosage, it induces a dissociative state similar to schizophrenia. The discovery of this effect on dissociative state has led to its use as a pharmacological model of schizophrenia and has also been responsible for its illegal use as a recreational drug. Whereas the former has provided invaluable information, the latter has demonstrated that repeated administration of ketamine induces tolerance. Surprisingly, a review of the relevant literature shows that tolerance to sub anaesthetic doses of ketamine is largely unreported in neuropharmacological studies. METHODS: In order to investigate this caveat, we have performed a post hoc analysis of the behavioural effects induced by repeated injections of sub anaesthetic doses of ketamine observed in five consecutive monkeys performing two oculomotor tasks. Ketamine effects were quantified by the animals' performances and latencies in a prosaccade and an antisaccade task, two oculomotor paradigms that are impaired after ketamine administration. RESULTS: Although the result of the initial injections confirmed a clear behavioural effect of ketamine injections in all monkeys, subsequent administrations showed that a tolerance eventually appeared in all monkeys. The profile of this tolerance exhibited however a large inter-subject variability. CONCLUSIONS: Psychopharmacological experiments using ketamine as a pharmacological model of psychosis should therefore consider the kinetic and time course of these effects in each individuals and take them into account in the design of experimental protocols. PMID- 20309531 TI - Nicotine modulation of information processing is not limited to input (attention) but extends to output (intention). AB - RATIONALE: Nicotine influences many cognitive processes, especially those requiring high attentional loads, yet the impact of nicotine on all aspects of information processing has not been well delineated. OBJECTIVE: The aim of the study was to determine the relative behavioral and functional effects of nicotine on dissociable aspects of information processing (i.e., selective attention and motor intention). METHODS: Adult smokers (N = 25) and healthy controls (N = 23) performed the intention/attention task (IAT) twice, during functional magnetic resonance imaging. The IAT assesses the relative differences in performance evoked by prime stimuli that provide information regarding either the correct hand with which to respond (i.e., intentional primes) or the likely location of a target stimulus (i.e., attentional primes). Smokers were scanned 2 h after nicotine (21 mg) or placebo patch placement. The order of nicotine and placebo sessions was randomized and counter-balanced. Controls were also scanned twice, with no patch placement in either session. RESULTS: While drug condition had no significant effect on reaction time, smokers were overall more accurate than controls. Moreover, nicotine significantly increased the response to intentional primes in brain regions known to mediate response readiness, e.g., inferior parietal lobe, supramarginal gyrus, and striatum. CONCLUSIONS: While limited to participant accuracy, these data suggest that the behavioral effects of nicotine in smokers are not only limited to information processing input (i.e., selective attention) but are also generalizable to output functions (i.e., motor intention). Moreover, nicotine's effects on intention appear to be mediated by a facilitation of function in brain regions associated with information processing output. PMID- 20309532 TI - Complication rate in unprotected carotid artery stenting with closed-cell stents. AB - INTRODUCTION: The discussion on the use of protection devices (PDs) in carotid artery stenting (CAS) is gaining an increasing role in lowering the periprocedural complication rates. While many reviews and reports with retrospective data analysis do promote the use of PDs the most recent multi centre trials are showing advantages for unprotected CAS combined with closed cell stent designs. METHODS: We retrospectively analysed 358 unprotected CAS procedures performed from January 2003 to June 2009 in our clinic. Male/female ratio was 2.68/1. The average age was 69.3 years. Seventy-three percent (261/358) showed initial neurological symptoms. All patients were treated on a standardised interventional protocol. A closed and small-sized cell designed stent was implanted in most cases (85.2%). One hundred seventy-one (47.8%) were controlled by Doppler ultrasonography usually at first in a 3-month and later in 6-month intervals. RESULTS: The peri-interventional and 30-day mortality/stroke rate was 4.19% (15/358). These events included three deaths, five hyperperfusion syndromes (comprising one death by a secondary fatal intracranial haemorrhage), one subarachnoid haemorrhage and seven ischaemic strokes. Only 20% (3/15) of all complications occurred directly peri-interventional. The overall peri interventional complication rate was 0.8% (3/358). Most complications occurred in initial symptomatic patients (5.36%). The in-stent restenosis rate for more than 70% was 7% (12/171) detected at an average of 9.8 month. CONCLUSION: Our clinical outcome demonstrates that unprotected CAS with small cell designed stents results in a very low procedural complication rate, which makes the use of a protection device dispensable. PMID- 20309533 TI - Optimum b value for resolving crossing fibers: a study with standard clinical b value using 1.5-T MR. AB - INTRODUCTION: We sought to investigate the optimum b value for resolving crossing fiber using high-angular resolution diffusion imaging (HARDI)-based multi-tensor tractography. The study tested the standard b values that are commonly used in the routine clinical setting. METHODS: Ten normal volunteers (five men and five women) with a mean age of 26.3 years (range, 22-32 years) were scanned using a 1.5-T clinical magnetic resonance unit. Single-shot echo-planar imaging was used for diffusion-weighted imaging with a diffusion-sensitizing gradient in 32 orientations. The b values of 700, 1,400, 2,100, and 2,800 s/m(2) were used. Data postprocessing was performed using multi-tensor methods. The depiction of the optic nerves, optic tracts, and decussation of superior cerebellar peduncles were assessed. RESULTS: The depictions of the nerve fibers were independent of the b values tested. CONCLUSION: The depiction of crossing fibers by HARDI-based multi tensor tractography is not substantially influenced by b values ranging from 700 to 2,800 s/m(2). Thus, the optimum b value within this range may be the lowest one considering the higher signal to noise ratio. PMID- 20309534 TI - Persistent primitive trigeminal arteries (PTA) and its variant (PTAV): analysis of 103 cases detected in 16,415 cases of MRA over 3 years. AB - INTRODUCTION: The primitive persistent trigeminal artery (PTA) is the most common carotid-basilar anastomosis, but because of its extremely low incidence, it is poorly understood. The purpose of this study is to clarify the features of PTA and its variants (PTAV) based on a large magnetic resonance angiography (MRA) series. METHODS: MRA was performed on continuous 16,415 patients (8,610 males and 7,805 females) between October 2005 and September 2008 using two 1.5-T systems and one 1.0-T system. These all MRAs were evaluated by neuroradiologists. RESULTS: The incidence of both PTA and PTAV was 0.68% (48 cases of PTA, 50 cases of PTAV, and five unclassified). Among them, 65 cases originated from the left internal carotid artery and 38 from the right. There were 44 cases of lateral type PTA and four cases of medial type. Hypoplasia of the basilar artery proximal to the union of PTA was recognized as follows: no hypoplasia in 12 cases, moderate hypoplasia in 22 cases, and severe hypoplasia in 13 cases. Distance from SCA and the union was an average of 6.7 mm. Four cases of pre- and postoperative cerebral aneurysms were recognized in 103 cases (3.9%). CONCLUSION: We have identified details of both PTA/PTAV. The incidence of PTA was similar to previous studies, and the co-existence of cerebral aneurysm was also similar when compared to patients in the general population without PTA or PTAV. PMID- 20309535 TI - Large endolymphatic sac anomaly. PMID- 20309536 TI - CT and MR imaging for pediatric cochlear implantation: emphasis on the relationship between the cochlear nerve canal and the cochlear nerve. AB - BACKGROUND: Cochlear implantation has become an accepted treatment for deafness. As the frequency of cochlear implantation has increased, requests for images have also increased in the work-up for candidates. An absent cochlear nerve (CN) is a contraindication to cochlear implantation. Therefore, MRI is performed to evaluate the CN in patients with sensorineural hearing loss. Recently, some authors have reported the relationship between cochlear nerve canal (CNC) stenosis and CN hypoplasia. OBJECTIVE: To review the relationship between CNC and CN. MATERIALS AND METHODS: During a period of 78 months, 21 children (42 ears) with unilateral or bilateral sensorineural hearing loss underwent both HRCT and MRI of the cochlear nerve. We retrospectively reviewed two factors: the evaluation of inner ear malformations and the relationship between CNC stenosis and CN hypoplasia. RESULTS: Inner ear malformations were recognized in ten ears. The mean CNC diameter was approximately 2 mm (ranging from 0.6 to 2.7 mm). CN hypoplasia was seen in eight of the 42 ears; all eight were associated with CNC stenosis (1.5 mm in diameter and the remaining two ears, with incomplete partition type I, had CNC stenosis. CONCLUSION: Children with CNC stenosis had a high incidence of CN hypoplasia. CNC stenosis (1.5 mm. Therefore, we conclude that children with CNC stenosis or malformations on HRCT should receive MR imaging of the CN. PMID- 20309537 TI - Fetal tumors: imaging features. AB - Although fetal tumors are rare, the prognostic and decision-making implications are substantial. The purpose of this pictorial essay is to highlight the most common tumors encountered during fetal imaging and to discuss the respective typical imaging findings. When appropriate, limited additional information regarding further considerations for patient care will be included. PMID- 20309538 TI - Antimicrobial resistance of the coral pathogen Vibrio coralliilyticus and Caribbean sister phylotypes isolated from a diseased octocoral. AB - Vibrio coralliilyticus is a global marine pathogen that has been found to cause disease in several marine organisms, including corals. This study is the first report of the isolation of V. coralliilyticus from a diseased Caribbean octocoral, Pseudopterogorgia americana. Five sister phylotypes were positively identified using 16S rRNA gene sequencing, recA probes specific for V. coralliilyticus, and rep-PCR fingerprinting. The antimicrobial resistance was compared between pathogenic strains of V. coralliilyticus and the Caribbean strains. First, the antimicrobial resistance of V. coralliilyticus-type strain ATCC BAA-450 was determined using an agar-overlay antimicrobial bioassay at 24 degrees C and 27 degrees C, temperatures which are relevant to its known temperature-dependent virulence. From 108 distinct bacteria isolated from P. americana, 12 inhibited the V. coralliilyticus-type strain at 24 degrees C and five at 27 degrees C. Next, the phenotypic comparison of two Caribbean phylotypes and three V. coralliilyticus reference strains against a subset of 30 bacteria demonstrated a similar resistance trend. At both temperatures, the reference strains were inhibited by three bacteria isolates, while the Caribbean strains were inhibited by four to nine bacteria. Additionally, V. coralliilyticus-type strain ATCC BAA-450 and one of the Caribbean strains were inhibited by a higher number of bacteria at 24 degrees C compared with 27 degrees C. Together, these results highlight that V. coralliilyticus strains have antimicrobial resistance to the majority of coral-associated bacteria tested, which may be temperature dependent in some strains. Furthermore, all V. coralliilyticus strains tested showed multi-drug resistance to a range of 11-16 (out of 26) commercial antibiotics. This study establishes V. coralliilyticus in association with a Caribbean octocoral and demonstrates its resistance to the antimicrobial activity of coral-associated bacteria and to commercial antibiotics. PMID- 20309539 TI - High-level production of heterologous proteins using untreated cane molasses and corn steep liquor in Escherichia coli medium. AB - To develop an economical industrial medium, untreated cane molasses (UCM) was tested as a carbon source for fermentation culturing of Escherichia coli. To test the industrial application of this medium, we chose a strain co-expressing a carbonyl reductase (PsCR) and a glucose dehydrogenase (BmGDH). Although corn steep liquor (CSL) could be used as an inexpensive nitrogen source to replace peptone, yeast extract could not be replaced in E. coli media. In a volume of 40 ml per 1-l flask, a cell concentration of optical density (OD(600)) 15.1 and enzyme activities of 6.51 U/ml PsCR and 3.32 U/ml BmGDH were obtained in an optimized medium containing 25.66 g/l yeast extract, 3.88 g/l UCM, and 7.1% (v/v) CSL. When 3.88 g/l UCM was added to the medium at 6 h in a fed-batch process, the E. coli concentration increased to OD(600) of 24, and expression of both PsCR and BmGDH were twofold higher than that of a batch process. Recombinant cells from batch or fed-batch cultures were assayed for recombinant enzyme activity by testing the reduction of ethyl 4-chloro-3-oxobutanoate to ethyl (S)-4-chloro-3 hydroxybutanoate (CHBE). Compared to cells from batch cultures, fed-batch cultured cells showed higher recombinant enzyme expression, producing 560 mM CHBE in the organic phase with a molar yield of 92% and an optical purity of the (S) isomer of >99% enantiomeric excess. PMID- 20309540 TI - Single-cell analysis and isolation for microbiology and biotechnology: methods and applications. AB - Various single-cell isolation techniques, including dilution, micromanipulation, flow cytometry, microfluidics, and compartmentalization, have been developed. These techniques can be used to cultivate previously uncultured microbes, to assess and monitor cell physiology and function, and to screen for novel microbiological products. Various other techniques, such as viable staining, in situ hybridization, and those using autofluorescence proteins, are frequently combined with these single-cell isolation techniques depending on the purpose of the study. In this review article, we summarize currently available single-cell isolation techniques and their applications, when used in combination with other techniques, in microbiological and biotechnological studies. PMID- 20309541 TI - Investigation of factors influencing spore germination of Paenibacillus polymyxa ACCC10252 and SQR-21. AB - Bioorganic fertilizer containing Paenibacillus polymyxa SQR-21 showed very good antagonistic activity against Fusarium oxysporum. To optimize the role of P. polymyxa SQR-21 in bioorganic fertilizer, we conducted a study of spore germination under various conditions. In this study, L-asparagine, glucose, fructose and K(+) (AGFK), and sugars (glucose, fructose, sucrose, and lactose) plus L-alanine were evaluated to determine their ability to induce spore germination of two strains; P. polymyxa ACCC10252 and SQR-21. Spore germination was measured as a decrease in optical density at 600 nm. The effect of heat activation and germination temperature were important for germination of spores of both strains on AGFK in Tris-HCl. L-Alanine alone showed a slight increase in spore germination; however, fructose plus L-alanine significantly induced spore germination, and the maximum spore germination rate was observed with 10 mmol l( 1) L-alanine in the presence of 1 mmol l(-1) fructose in phosphate-buffered saline (PBS). In contrast, fructose plus L-alanine hardly induced spore germination in Tris-HCl; however, in addition of 10 mmol l(-1) NaCl into Tris HCl, the percentages of OD(600) fall were increased by 19.6% and 24.3% for ACCC10252 and SQR-21, respectively. AGFK-induced spore germination was much more strict to germination temperature than that induced by fructose plus L-alanine. For both strains, fructose plus L-alanine-induced spore germination was not sensitive to pH. The results in this study can help to predict the effect of environmental factors and nutrients on spore germination diversity, which will be beneficial for bioorganic fertilizer storage and transportation to improve the P. polymyxa efficacy as biological control agent. PMID- 20309542 TI - Transcriptome shifts in response to furfural and acetic acid in Saccharomyces cerevisiae. AB - Furfural and acetic acid are two prevalent inhibitors to microorganisms during cellulosic ethanol production, but molecular mechanisms of tolerance to these inhibitors are still unclear. In this study, genome-wide transcriptional responses to furfural and acetic acid were investigated in Saccharomyces cerevisiae using microarray analysis. We found that 103 and 227 genes were differentially expressed in the response to furfural and acetic acid, respectively. Furfural downregulated genes related to transcriptional control and translational control, while it upregulated stress-responsive genes. Furthermore, furfural also interrupted the transcription of genes involved in metabolism of essential chemicals, such as etrahydrofolate, spermidine, spermine, and riboflavin monophosphate. Acetic acid downregulated genes encoding mitochondrial ribosomal proteins and genes involved in carbohydrate metabolism and regulation and upregulated genes related to amino acid metabolism. The results revealed that furfural and acetic acid had effects on multiple aspects of cellular metabolism on the transcriptional level and that mitochondria might play important roles in response to both furfural and acetic acid. This research has provided insights into molecular response to furfural and acetic acid in S. cerevisiae, and it will be helpful to construct more resistant strains for cellulosic ethanol production. PMID- 20309543 TI - Genetic and metabolic engineering of isoflavonoid biosynthesis. AB - Isoflavonoids are a diverse group of secondary metabolites derived from the phenylpropanoid pathway. These compounds are distributed predominantly in leguminous plants and play important roles in plant-environment interactions and human health. Consequently, the biosynthetic pathway of isoflavonoid compounds has been widely elucidated in the past decades. Up to now, most of the structural genes and some of the regulatory genes involved in this pathway have been isolated and well characterized. Nowadays, the protective effects of the legume isoflavonoids against hormone dependent cancers, cardiovascular disease, osteoporosis, and menopausal symptoms have generated considerable interest within the genetic and metabolic engineering fields to enhance the dietary intake of these compounds for disease prevention. Subsequently, there are some great progresses in genetic and metabolic engineering to improve their yields in leguminous and non-leguminous plants and/or microorganisms. Because of the field of flavonoid biosynthesis has been reviewed fairly extensively in the past, this review concentrates on the more recent development in the isoflavonoid branch of phenylpropanoid pathway, including gene isolation and characterization. In addition, we describe the state-of-the-art research with respect to genetic and metabolic engineering of isoflavonoid biosynthesis. PMID- 20309544 TI - Comparative analysis of membranous proteomics of Shewanella decolorationis S12 grown with azo compound or Fe (III) citrate as sole terminal electron acceptor. AB - Shewanella decolorationis S12 is capable of carrying out anaerobic respiration using azo dyes and Fe (III) citrate as electron acceptors. In the present study, proteomic techniques including two-dimensional gel electrophoresis (2-DE) and matrix-assisted laser desorption/ionization time-of-flight/time-of-flight mass spectrometry were used to analyze the similarity and the dissimilarity of the membrane proteins isolated from strain S12 cells grown in amaranth or Fe (III) citrate with defined inorganic salt medium. The cells of strain S12 grown under a saturated dissolved oxygen condition served as controls. This is the first work that made the comparative analysis of cell membranous proteomics of strain S12 grown with azo compound or Fe (III) citrate as a sole terminal electron acceptor. The results showed that most of the membrane proteins of strain S12 under azo respiration are similar to those under Fe (III) respiration, but dissimilar from those of oxygen-grown cells. FdnH and FrdB were expressed specifically in azo respiration. NqrA-2, DctP, and hypothetical protein SO_4719 showed relative overexpression in azo respiration compared with Fe (III) respiration. OmpA family protein SO_3545 was detected to be specific to Fe (III) respiration. Furthermore, ArgF, SdhA, and HoxK were expressed markedly in both amaranth- and Fe (III) citrate-grown cultures compared with oxygen-grown cultures. PMID- 20309545 TI - Kaposiform hemangioendothelioma arising in the deltoid muscle without the Kasabach-Merritt phenomenon. AB - Kaposiform hemangioendothelioma (KHE) is a rare tumor that occurs nearly exclusively during infancy and childhood. It has features common to both capillary hemangioma and Kaposi sarcoma and for that reason many terms have been used for these tumors including "Kaposi-like infantile hemangioendothelioma" and "hemangioma with Kaposi sarcoma-like features." KHE typically presents as an ill defined, red to purple, indurated plaque and is often complicated by the Kasabach Merritt phenomenon (KMP), a condition of severe thrombocytopenia and consumptive coagulopathy. Knowledge of the radiological findings of this uncommon tumor might be helpful for diagnosis. We present the MRI features of a case of KHE with neither typical skin lesions nor the Kasabach-Merritt phenomenon. PMID- 20309546 TI - Epitope distance to the target cell membrane and antigen size determine the potency of T cell-mediated lysis by BiTE antibodies specific for a large melanoma surface antigen. AB - Melanoma chondroitin sulfate proteoglycan (MCSP; also called CSPG4, NG2, HMW-MAA, MSK16, MCSPG, MEL-CSPG, or gp240) is a surface antigen frequently expressed on human melanoma cells, which is involved in cell adhesion, invasion and spreading, angiogenesis, complement inhibition, and signaling. MCSP has therefore been frequently selected as target antigen for development of antibody- and vaccine based therapeutic approaches. We have here used a large panel of monoclonal antibodies against human MCSP for generation of single-chain MCSP/CD3-bispecific antibodies of the BiTE (for bispecific T cell engager) class. Despite similar binding affinity to MCSP, respective BiTE antibodies greatly differed in their potency of redirected lysis of CHO cells stably transfected with full-length human MCSP, or with various MCSP deletion mutants and fusion proteins. BiTE antibodies binding to the membrane proximal domain D3 of MCSP were more potent than those binding to more distal domains. This epitope distance effect was corroborated with EpCAM/CD3-bispecific BiTE antibody MT110 by testing various fusion proteins between MCSP and EpCAM as surface antigens. CHO cells expressing small surface target antigens were generally better lysed than those expressing larger target antigens, indicating that antigen size was also an important determinant for the potency of BiTE antibody. The present study for the first time relates the positioning of binding domains and size of surface antigens to the potency of target cell lysis by BiTE-redirected cytotoxic T cells. In case of the MCSP antigen, this provides the basis for selection of a maximally potent BiTE antibody candidate for development of a novel melanoma therapy. PMID- 20309547 TI - Upscaling of environmental information: support of land-use management decisions by spatio-temporal regionalization approaches. AB - This article presents several case studies in southwest Germany, which aimed to support land use management decisions by a process-oriented statistical upscaling of point-related environmental monitoring data to the landscape scale. When techniques of data subsetting were used in a sensible way and corresponding to the appropriate scale for the evaluation envisaged, multiple linear regression offered a data mining technique which was able to spatially predict relatively complex environmental patterns with parsimonious, interpretable and accurate models, whereby different evaluation scales were best represented by different DTM resolutions. Scenario models based upon the regression formulas were a valuable tool for visualizing management options and evaluating management impacts (tree species selection) on soil functions (carbon storage), which qualifies the presented methodology as a useful aid in decision making. Such upscaling techniques may be used for forecasting long-term effects of ecosystem management, but they provided no information on temporal dynamics. Therefore, time trends of point information on soil solution data were scaled by linking them to soil chemical data which was available in higher spatial resolution, using both statistical and process-oriented methods. PMID- 20309548 TI - New strategy of endothelial protection in cardiac surgery: use of enhancer of endothelial nitric oxide synthase. AB - BACKGROUND: Endothelial dysfunction related to the loss of nitric oxide (NO) production remains an important issue in cardiac surgery. We examined the hypothesis that AVE3085, a novel compound that enhances eNOS transcription, may protect coronary endothelium against hypoxia-reoxygenation (H-R) injury during cardioplegic arrest and the possible mechanism by which this occurs. METHODS: Porcine coronary small arteries (600-800-microm diameter) were subjected to hypoxia (PO(2) <5 mmHg) in St. Thomas cardioplegic (ST) solution with or without AVE3085 (10 microM) or L-arginine (10 mM) at either 37 or 4 degrees C for 60 min, followed by 30-min reoxygenation. Bradykinin (-10 to -6.5 LogM)-induced, endothelium-dependent relaxation was studied in a myograph in U(46619) precontraction before and after H-R. Protein expressions of eNOS and phosphorylated eNOS at Ser-1177 (p-eNOS(Ser1177)) were also determined. RESULTS: Exposure to ST solution with H-R at both 37 and 4 degrees C markedly reduced bradykinin-induced relaxation in coronary small arteries. Addition of AVE3085 in ST solution at 37 degrees C preserved the vasorelaxant response to bradykinin (95.7 +/- 2.1% vs. 69.2 +/- 6.6%, p < 0.01), with the protective effect comparable to that of L-arginine (96.1 +/- 3.3% vs. 70.6 +/- 8.7%, p < 0.05). eNOS and p-eNOS(Ser1177) expressions in coronary endothelial cells were significantly increased by the addition of AVE3085 in ST solution during hypoxia (p < 0.05). Protection of endothelium-dependent relaxation from H-R by AVE3085 (70.3 +/- 7.2% vs. 90.5 +/- 2.4%, p < 0.05) also reached a level similar to that by L-arginine (69.9 +/- 9.0% vs. 94.7 +/- 3.9%, p < 0.05) at 4 degrees C. CONCLUSIONS: We have demonstrated a new mechanism to protect coronary endothelium from H-R injury by using eNOS enhancers. This may form a new strategy in the future development of cardioplegic/preservation solutions with direct targeting of eNOS expression in coronary vasculature. PMID- 20309549 TI - A note on a paper by Erik Volz: SIR dynamics in random networks. AB - Recent work by Volz (J Math Biol 56:293-310, 2008) has shown how to calculate the growth and eventual decay of an SIR epidemic on a static random network, assuming infection and recovery each happen at constant rates. This calculation allows us to account for effects due to heterogeneity and finiteness of degree that are neglected in the standard mass-action SIR equations. In this note we offer an alternate derivation which arrives at a simpler-though equivalent-system of governing equations to that of Volz. This new derivation is more closely connected to the underlying physical processes, and the resulting equations are of comparable complexity to the mass-action SIR equations. We further show that earlier derivations of the final size of epidemics on networks can be reproduced using the same approach, thereby providing a common framework for calculating both the dynamics and the final size of an epidemic spreading on a random network. Under appropriate assumptions these equations reduce to the standard SIR equations, and we are able to estimate the magnitude of the error introduced by assuming the SIR equations. PMID- 20309550 TI - A stochastic SIS epidemic with demography: initial stages and time to extinction. AB - We study an open population stochastic epidemic model from the time of introduction of the disease, through a possible outbreak and to extinction. The model describes an SIS (susceptible-infective-susceptible) epidemic where all individuals, including infectious ones, reproduce at a given rate. An approximate expression for the outbreak probability is derived using a coupling argument. Further, we analyse the behaviour of the model close to quasi-stationarity, and the time to disease extinction, with the aid of a diffusion approximation. In this situation the number of susceptibles and infectives behaves as an Ornstein Uhlenbeck process, centred around the stationary point, for an exponentially distributed time before going extinct. PMID- 20309551 TI - Complete sequence of the mitochondrial genome of a diatom alga Synedra acus and comparative analysis of diatom mitochondrial genomes. AB - The first two mitochondrial genomes of marine diatoms were previously reported for the centric Thalassiosira pseudonana and the raphid pennate Phaeodactylum tricornutum. As part of a genomic project, we sequenced the complete mitochondrial genome of the freshwater araphid pennate diatom Synedra acus. This 46,657 bp mtDNA encodes 2 rRNAs, 24 tRNAs, and 33 proteins. The mtDNA of S. acus contains three group II introns, two inserted into the cox1 gene and containing ORFs, and one inserted into the rnl gene and lacking an ORF. The compact gene organization contrasts with the presence of a 4.9-kb-long intergenic region, which contains repeat sequences. Comparison of the three sequenced mtDNAs showed that these three genomes carry similar gene pools, but the positions of some genes are rearranged. Phylogenetic analysis performed with a fragment of the cox1 gene of diatoms and other heterokonts produced a tree that is similar to that derived from 18S RNA genes. The introns of mtDNA in the diatoms seem to be polyphyletic. This study demonstrates that pyrosequencing is an efficient method for complete sequencing of mitochondrial genomes from diatoms, and may soon give valuable information about the molecular phylogeny of this outstanding group of unicellular organisms. PMID- 20309552 TI - Differentiation between hepatic haemangiomas and cysts with an inversion recovery single-shot turbo spin-echo (SSTSE) sequence using the TI nulling value of hepatic haemangioma with sensitivity encoding. AB - OBJECTIVE: To evaluate the additional value of inversion recovery (IR) single shot turbo spin-echo (SSTSE) imaging with sensitivity encoding (SENSE) using the inversion time (TI) value of hepatic haemangioma as a supplement to conventional T2-weighted turbo spin-echo (TSE) imaging for the discrimination of hepatic haemangiomas and cysts. METHODS: A total of 134 lesions (77 hepatic haemangiomas, 57 hepatic cysts) in 59 patients were evaluated. Three readers evaluated these images and used a five-point scale to evaluate the lesion status. A receiver operating characteristic (ROC) analysis and 2 x 2 table analysis were used. RESULTS: The ROC analysis for all the readers and all the cases revealed a significantly higher area under the curve (AUC) for the combination of moderately and heavily T2-weighted TSE with IR-SSTSE images (0.945) than for moderately and heavily T2-weighted TSE images alone (0.894) (P < 0.001). For the combination of T2-weighted TSE with IR-SSTSE versus T2-weighted TSE alone, the 2 x 2 table analysis revealed a higher true-positive rate; this difference was statistically significant (P < 0.0001). CONCLUSION: The introduction of IR-SSTSE with SENSE sequences significantly improves the diagnostic accuracy of the differentiation of hepatic haemangioma and cysts while increasing the time required for routine abdominal imaging by only 20 s. PMID- 20309553 TI - Squamous cell carcinoma of the head and neck: diffusion-weighted MR imaging for prediction and monitoring of treatment response. AB - OBJECTIVE: To investigate the role of diffusion-weighted imaging (DWI) in predicting and monitoring chemoradiotherapy response in head and neck squamous cell carcinoma (HNSCC). METHODS: Diffusion-weighted imaging was performed pre treatment (n = 50), intra-treatment (n = 41) and post-treatment (n = 20). Apparent diffusion coefficient (ADC) values were correlated with locoregional failure (LF). RESULTS: Locoregional failure occurred in 20/50 (40%) patients. A significant correlation was found between LF and post-treatment ADC (p = 0.02) but not pre- or intra-treatment ADC. Serial change in ADC was even more significant (p = 0.00001), using a fall in ADC early (pre- to intra-treatment) or late (intra- to post-treatment) to indicate LF, achieved 100% specificity, 80% sensitivity and 90% accuracy. CONCLUSIONS: Single ADC measurements pre- or intra treatment did not predict response, but ADC post-treatment was a marker for LF. Serial change in ADC was an even stronger marker, when using an early or late treatment fall in ADC to identify LF. PMID- 20309554 TI - Spectroscopic (multi-energy) CT distinguishes iodine and barium contrast material in MICE. AB - OBJECTIVE: Spectral CT differs from dual-energy CT by using a conventional X-ray tube and a photon-counting detector. We wished to produce 3D spectroscopic images of mice that distinguished calcium, iodine and barium. METHODS: We developed a desktop spectral CT, dubbed MARS, based around the Medipix2 photon-counting energy-discriminating detector. The single conventional X-ray tube operated at constant voltage (75 kVp) and constant current (150 microA). We anaesthetised with ketamine six black mice (C57BL/6). We introduced iodinated contrast material and barium sulphate into the vascular system, alimentary tract and respiratory tract as we euthanised them. The mice were preserved in resin and imaged at four detector energy levels from 12 keV to 42 keV to include the K-edges of iodine (33.0 keV) and barium (37.4 keV). Principal component analysis was applied to reconstructed images to identify components with independent energy response, then displayed in 2D and 3D. RESULTS: Iodinated and barium contrast material was spectrally distinct from soft tissue and bone in all six mice. Calcium, iodine and barium were displayed as separate channels on 3D colour images at <55 microm isotropic voxels. CONCLUSION: Spectral CT distinguishes contrast agents with K edges only 4 keV apart. Multi-contrast imaging and molecular CT are potential future applications. PMID- 20309555 TI - Electronic cleansing for CT colonography: does it help CAD software performance in a high-risk population for colorectal cancer? AB - OBJECTIVE: To compare the performance of computer-aided detection (CAD) for CT colonography (CTC) with and without electronic cleansing (EC) in a high-risk population tagged with a faecal tagging (FT) protocol. METHODS: Thirty-two patients underwent CTC followed by same-day colonoscopy. All patients underwent bowel preparation and FT with barium and gastrografin. Each CTC dataset was processed with colon CAD with and without EC. Per-polyp sensitivity was calculated. The average number of false-positive (FP) results and their causes were also analysed and compared. RESULTS: Eighty-six polyps were detected in 29 patients. Per-polyp sensitivities of CAD with EC (93.8% and 100%) were higher than those without EC (84.4% and 87.5%) for polyps >or=6 mm and >or=10 mm, respectively. However, the differences were not significant. The average number (6.3) of FPs of CAD with EC was significantly larger than that (3.1) without EC. The distribution of FPs in both CAD settings was also significantly different. The most common cause of FPs was the ileocaecal valve in both datasets. However, untagged faeces was a significantly less common cause of FPs with EC, EC-related artefacts being more common. CONCLUSION: Electronic cleansing has the potential to improve per-polyp sensitivity of CTC CAD, although the significantly larger number of FPs with EC remains to be improved. PMID- 20309556 TI - 3D 23Na MRI of human skeletal muscle at 7 Tesla: initial experience. AB - OBJECTIVE: To evaluate healthy skeletal muscle pre- and post-exercise via 7 T (23)Na MRI and muscle proton T(2) mapping, and to evaluate diabetic muscle pre- and post-exercise via 7 T (23)Na MRI. METHODS: The calves of seven healthy subjects underwent imaging pre- and post-exercise via 7 T (23)Na MRI (3D fast low angle shot, TR/TE = 80 ms/0.160 ms, 4 mm x 4 mm x 4 mm) and 1 week later by (1)H MRI (multiple spin-echo sequence, TR/TE = 3,000 ms/15-90 ms). Four type 2 diabetics also participated in the (23)Na MRI protocol. Pre- and post-exercise sodium signal intensity (SI) and proton T(2) relaxation values were measured/calculated for soleus (S), gastrocnemius (G), and a control, tibialis anterior (TA). Two-tailed t tests were performed. RESULTS: In S/G in healthy subjects post-exercise, sodium SI increased 8-13% (p < 0.03), then decreased (t(1/2) = 22 min), and (1)H T(2) values increased 12-17% (p < 0.03), then decreased (t(1/2 )= 12-15 min). In TA, no significant changes in sodium SI or (1)H T(2) values were seen (-2.4 to 1%, p > 0.17). In S/G in diabetics, sodium SI increased 10-11% (p < 0.04), then decreased (t(1/2) = 27-37 min) without significant change in the TA SI (-3.6%, p = 0.066). CONCLUSION: It is feasible to evaluate skeletal muscle via 3D (23)Na MRI at 7 T. Post-exercise muscle (1)H T(2) values return to baseline more rapidly than sodium SI. Diabetics may demonstrate delayed muscle sodium SI recovery compared with healthy subjects. PMID- 20309557 TI - Chronic mitral regurgitation detected on cardiac MDCT: differentiation between functional and valvular aetiologies. AB - OBJECTIVE: To determine whether cardiac computed tomography (MDCT) can differentiate between functional and valvular aetiologies of chronic mitral regurgitation (MR) compared with echocardiography (TTE). METHODS: Twenty-seven patients with functional or valvular MR diagnosed by TTE and 19 controls prospectively underwent cardiac MDCT. The morphological appearance of the mitral valve (MV) leaflets, MV geometry, MV leaflet angle, left ventricular (LV) sphericity and global/regional wall motion were analysed. The coronary arteries were evaluated for obstructive atherosclerosis. RESULTS: All control and MR cases were correctly identified by MDCT. Significant differences were detected between valvular and control groups for anterior leaflet length (30 +/- 7 mm vs. 22 +/- 4 mm, P < 0.02) and thickness (3.0 +/- 1 mm vs. 2.2 +/- 1 mm, P < 0.01). High-grade coronary stenosis was detected in all patients with functional MR compared with no controls (P < 0.001). Significant differences in those with/without MV prolapse were detected in MV tent area (-1.0 +/- 0.6 mm vs. 1.3 +/- 0.9 mm, P < 0.0001) and MV tent height (-0.7 +/- 0.3 mm vs. 0.8 +/- 0.8 mm, P < 0.0001). Posterior leaflet angle was significantly greater for functional MR (37.9 +/- 19.1 degrees vs. 22.9 +/- 14 degrees , P < 0.018) and less for valvular MR (0.6 +/- 35.5 degrees vs. 22.9 +/- 14 degrees, P < 0.017). Sensitivity, specificity, and positive and negative predictive values of MDCT were 100%, 95%, 96% and 100%. CONCLUSION: Cardiac MDCT allows the differentiation between functional and valvular causes of MR. PMID- 20309558 TI - Whole-body diffusion-weighted magnetic resonance imaging with apparent diffusion coefficient mapping for staging patients with diffuse large B-cell lymphoma. AB - OBJECTIVE: To design a whole-body MR protocol using exclusively diffusion weighted imaging (DWI) with respiratory gating and to assess its value for lesion detection and staging in patients with diffuse large B-cell lymphoma (DLBCL), with integrated FDG PET/CT as the reference standard. METHODS: Fifteen patients underwent both whole-body DWI (b = 50, 400, 800 s/mm(2)) and PET/CT for pretreatment staging. Lymph node and organ involvement were evaluated by qualitative and quantitative image analysis, including measurement of the mean apparent diffusion coefficient (ADC). RESULTS: A total of 296 lymph node regions in the 15 patients were analysed. Based on International Working Group size criteria alone, DWI findings matched PET/CT findings in 277 regions (94%) (kappa score = 0.85, P < 0.0001), yielding sensitivity and specificity for DWI lymph node involvement detection of 90% and 94%. Combining visual ADC analysis with size measurement increased DWI specificity to 100% with 81% sensitivity. For organ involvement, the two techniques agreed in all 20 recorded organs (100%). All involved organ lesions showed restricted diffusion. Ann Arbor stages agreed in 14 (93%) of the 15 patients. CONCLUSION: Whole-body DWI with ADC analysis can potentially be used for lesion detection and staging in patients with DLBCL. PMID- 20309559 TI - Real-time contrast-enhanced ultrasound-guided biopsy of focal hepatic lesions not localised on B-mode ultrasound. AB - OBJECTIVE: To prospectively evaluate the technical feasibility of percutaneous real-time contrast-enhanced ultrasound (CEUS) guided biopsy of focal hepatic lesions that are not confidently localised on B-mode US. METHODS: The study included 44 patients (mean age, 61.3 years) whose biopsy target could not be confidently localised on B-mode US performed by two independent radiologists. Biopsy was attempted under the guidance of both CEUS and B-mode US simultaneously displayed on a single monitor. Final diagnosis was established based on the pathological examination of the biopsy specimen as well as on clinical and radiological follow-up. RESULTS: The size and depth of the target lesions were 18.0 +/- 9.0 mm (mean +/- SD) and 41.8 +/- 17.2 mm respectively. Five patients with negative or indistinct CEUS findings did not undergo biopsy, while 39 patients completed the biopsy. In 38 of the 39 patients, the biopsy result was concordant with the final diagnosis. In the remaining one patient, the biopsy failed to prove metastasis. As there were six cases of technical failure, the technical success rate was 86% (38/44). The sensitivity in diagnosing malignancy was 88% (30/34). CONCLUSION: Real-time CEUS-guided biopsy is technically feasible for hepatic focal lesions that are not confidently localised on B-mode US. PMID- 20309560 TI - Screening for renal insufficiency following ESUR (European Society of Urogenital Radiology) guidelines with on-site creatinine measurements in an outpatient setting. AB - OBJECTIVE: To report the results and implications for workflow following introduction of ESUR guidelines to screen for potential renal insufficiency (RI) in private practice with on-site creatinine measurements. METHODS: A total of 1,766 consecutive outpatients scheduled for contrast-enhanced CT (CECT) completed the ESUR questionnaire enquiring about kidney disease, renal surgery, proteinuria, diabetes mellitus, hypertension, gout or use of nephrotoxic drugs. Patients with positive risk factors underwent on-site creatinine measurement and calculation of estimated glomerular filtration rate (eGFR). Attending radiologists adapted subsequent imaging depending on renal function and presence of risk factors. RESULTS: One or more ESUR risk factors were present in 796 (45.1%) patients, including hypertension (37.7%), nephrotoxic medication (21.3%), diabetes mellitus (8.0%), proteinuria (3.9%), renal disease (4.1%), gout (3.1%) and renal surgery (2.6%). Pre-procedural creatinine measurements revealed severe RI (eGFR < 30 ml min(-1) 1.73 m(-2)) in 10 (1.3%) and moderate RI (eGFR 30-59 ml min(-1) 1.73 m(-2)) in 106 (13.8%). Imaging work-up was adapted in 132 (16.6%) as follows: reduction of contrast material dose (n = 85), CT without contrast (n = 40), changeover to MRI (n = 3) or scintigraphy (n = 4). CONCLUSION: Screening for RI following ESUR guidelines requires creatinine measurements in nearly half of outpatients scheduled for CECT and reveals moderate to severe renal impairment in 6.6%. PMID- 20309561 TI - Persistent postpartum haemorrhage after failed arterial ligation: value of pelvic embolisation. AB - OBJECTIVES: To evaluate the role and efficacy of pelvic embolisation in the treatment of persistent postpartum haemorrhage after failed arterial ligation and to identify the complications of this procedure in this specific population. METHODS: The clinical files and angiographic examinations of 12 consecutive women (mean age 32 years) who were treated with pelvic embolisation because of persistent, severe postpartum haemorrhage after failed arterial ligation were reviewed. RESULTS: Angiography revealed that persistent bleeding was due to incomplete arterial ligation (n = 4) or the presence of newly developed anastomotic routes (n = 8). In 11 women, pelvic embolisation stopped the bleeding. Hysterectomy was needed in one woman with retained placenta. Two complications due to pelvic embolisation, including leg ischaemia and transient sciatic nerve ischaemia, were identified, both after internal iliac artery ligation. CONCLUSIONS: In women with persistent postpartum haemorrhage after failed arterial ligation, pelvic embolisation is an effective treatment in most cases. However, embolisation of the anastomotic routes that contribute to persistent bleeding may result in ischaemic complications. These potential complications reaffirm that arterial ligation should not be the favoured option for postpartum haemorrhage and that special care must be given during pelvic embolisation after failed arterial ligation. PMID- 20309562 TI - Clinical experience with survivin as a biomarker for urothelial bladder cancer. AB - OBJECTIVES: This study was carried out as a prospective pilot study to evaluate the potential of survivin mRNA measurement in patients suspicious for urothelial bladder cancer (BC). Data were also analyzed for possible influences of secondary urological findings on survivin measurements. METHODS: Survivin was measured by an mRNA assay in voided urine samples of 50 patients with suspicion of new or recurrent BC prior to transurethral resection. Sample evaluation was possible in 49 cases. Histopathology revealed no malignancy in 17 (35%) and BC in 32 (65%) patients. Survivin mRNA was quantitated by real-time PCR from frozen cell pellets of centrifuged urine samples. A ROC analysis of the survivin data was performed. RESULTS: ROC analysis identified the best cut-off level at 10,000 mRNA copies, resulting in a sensitivity of 53% and a specificity of 88%. Seven of the 20 pTa tumors (35%), all four pT1 (100%) and all four muscle-invasive tumors (100%) were detected. Of four patients with carcinoma in situ (Cis), 50% could be identified. Only two patients (4%) were assessed as false positive. Histologically confirmed cystitis and concomitant urological findings (inflammatory cells in urine, microhematuria and others) had no detectable influence on survivin measurements. CONCLUSION: In present group of patients, survivin was a reliable biomarker for high-grade urothelial BC (sensitivity 83%), but not for low grade (sensitivity 35%) urothelial BC with a high specificity (88%). No confounders influencing the results of survivin measurements could be identified. PMID- 20309563 TI - Clinical efficacy of a loading dose of naftopidil for patients with benign prostate hyperplasia. AB - PURPOSE: The efficacy of a loading dose of alpha(1)-adrenoreceptor antagonist for patients with benign prostate hyperplasia who did not improve at a low dose has not been determined. We performed a prospective study to estimate the efficacy of incremental naftopidil administration. METHODS: The efficacy of naftopidil was examined based on changes in the International Prostate Symptom Score (IPSS). We defined a "responder" as a patient who improved by >=5 points in IPSS total score. All patients were administered naftopidil at 50 mg/day for 12 weeks, and nonresponders at 50 mg/day were increased to 75 mg/day. Efficacy was finally evaluated after an additional 12 weeks of administration at 75 mg/day. RESULTS: Among 122 patients whose data could be analyzed, the efficacy rate after administration at 50 mg/day was 52.5%. In all IPSS items except urgency score, the responders had significantly higher (poorer) values than nonresponders before the start of treatment. Of 40 patients whose dose was increased to 75 mg/day and whose data could be analyzed, prostate volume in the responder group (9 patients) was significantly smaller than that in the nonresponder group (31 patients). Multivariate analysis showed that patients with improved IPSS total score, voiding symptoms, urgency, and weak stream after administration of 50 mg/day naftopidil were more likely to improve after a dose increase. CONCLUSIONS: A dose increment of naftopidil to 75 mg/day may be useful in patients with BPH who did not improve at 50 mg/day. PMID- 20309564 TI - Congenital pouch colon: antenatal diagnosis and video-assisted management. AB - Congenital pouch colon (CPC) is an unusual abnormality associating a pouch-like dilatation of a shortened colon with an anorectal malformation (ARM). There are few reports of CPC in Europe, a contrario it represents up to 15% of ARM in India. Coloplasty and excision are described in the surgical management. This report describes a new case of CPC. This is the first reported case with a prenatal clinical presentation as an hypoechogenic abdominal image at ultrasound and a video-assisted management. PMID- 20309565 TI - Clinical events after surgical splenectomy in children with sickle cell anemia. AB - PURPOSE: Despite advances in immune prophylaxis, sepsis remains the most feared complication following splenectomy for acute splenic sequestration crisis (ASSC) in children with sickle cell anemia (SCA). We seek to investigate the true prevalence of sepsis and other complications of splenectomy in this patient population. METHODS: We reviewed the records of children with SCA (HbSS) who underwent splenectomy for ASSC between 1993 and 2008 at a single institution. RESULTS: Fifty-eight patients (33 males) at a median age of 2 years at splenectomy were included with an average post-splenectomy follow-up of 6.4 years (range 6 months-14 years). Thirty-seven patients (64%) underwent laparoscopic splenectomy, and acute chest syndrome (ACS) was the most common post-operative complication (6.9%). There was no difference in the incidence of sepsis pre- and post-splenectomy. The occurrence of vaso-occlusive pain crises (VOC) and ACS was significantly higher after splenectomy. In addition, 14 patients (24%) developed stroke (n = 5) or an abnormal transcranial Doppler (TCD) (n = 9) after splenectomy. CONCLUSION: Our data suggest that splenectomy can be safely performed in children with SCA given a low risk of sepsis. However, the increased incidence of VOC, ACS, and stroke or abnormal TCDs after splenectomy remains a concern. PMID- 20309566 TI - The neuroinflammatory hypothesis of delirium. AB - Delirium is a neuropsychiatric syndrome characterized by a sudden and global impairment in consciousness, attention and cognition. It is particularly frequent in elderly subjects with medical or surgical conditions and is associated with short- and long-term adverse outcomes. The pathophysiology of delirium remains poorly understood as it involves complex multi-factorial dynamic interactions between a diversity of risk factors. Several conditions associated with delirium are characterized by activation of the inflammatory cascade with acute release of inflammatory mediators into the bloodstream. There is compelling evidence that acute peripheral inflammatory stimulation induces activation of brain parenchymal cells, expression of proinflammatory cytokines and inflammatory mediators in the central nervous system. These neuroinflammatory changes induce neuronal and synaptic dysfunction and subsequent neurobehavioural and cognitive symptoms. Furthermore, ageing and neurodegenerative disorders exaggerate microglial responses following stimulation by systemic immune stimuli such as peripheral inflammation and/or infection. In this review we explore the neuroinflammatory hypothesis of delirium based on recent evidence derived from animal and human studies. PMID- 20309567 TI - Von Economo neuron density in the anterior cingulate cortex is reduced in early onset schizophrenia. AB - The anterior cingulate cortex (ACC) represents a phylogenetically ancient region of the mammalian brain that has undergone recent adaptive changes in humans. It contains a large spindle-shaped cell type, referred to as von Economo neuron (VEN) that has been shown to be involved in the pathophysiology of various neuropsychiatric disorders. Schizophrenia is a group of disorders that is, in part, characterised by a disruption of neuronal migration in early ontogeny and presumably secondary degeneration after the first psychotic episode in some patients. Accordingly, we tested the hypothesis that the density of VENs is reduced in a neurodevelopmental subtype of schizophrenia, which we defined by an early onset of the disorder. The density of VENs was estimated in layer Vb of Brodmann's area 24 in 20 subjects diagnosed with schizophrenia. The results were compared with 19 specimens from patients with bipolar disorder as a clinical control and 22 non-psychiatric samples. The density of VENs did not differ between the three groups. However, the VEN density in the right ACC correlated with the age at onset, and inversely with the duration of the illness in schizophrenia, but not in bipolar disorder. Thus, patients with early onset schizophrenia (and longer duration of illness) had a reduced VEN density. Age, sex, postmortem interval, brain weight, and cortical thickness had no significant impact on the results. These findings suggest that VENs in the ACC are involved in neurodevelopmental and perhaps neurodegenerative processes specific to schizophrenia. PMID- 20309568 TI - Papp-Lantos inclusions and the pathogenesis of multiple system atrophy: an update. AB - Multiple systemic atrophy (MSA) is a progressive, adult-onset neurodegenerative disorder of undetermined aetiology characterized by a distinctive oligodendrogliopathy with argyrophilic glial cytoplasmic inclusions (GCIs) and selective neurodegeneration. GCIs or Papp-Lantos inclusions, described more than 20 years ago, are now accepted as the hallmarks for the definite neuropathological diagnosis of MSA and suggested to play a central role in the pathogenesis of this disorder. GCIs are composed of hyperphosphorylated alpha synuclein (alphaSyn), ubiquitin, LRRK2 (leucin-rich repeat serine/threonine protein) and many other proteins, suggesting that MSA represents an invariable synucleinopathy of non-neuronal type, a specific form of proteinopathies. The origin of alphaSyn deposition in GCIs is not yet fully understood, but recent findings of dysregulation in the metabolism of myelin basic protein (MBP) and p25alpha, a central nervous system-specific protein, also called TPPP (tubulin polymerization promoting protein), strengthened the working model of MSA as a primary glial disorder and may explain frequent alterations of myelin in MSA. However, it is unknown whether these changes represent an early event or myelin dysregulation occurs further downstream in MSA pathogenesis. The association between polymorphisms at the SNCA gene locus and the risk for developing MSA also points to a primary role of alphaSyn in its pathogenesis, while in a MBP promoter driven alphaSyn transgenic mouse model gliosis accompanied the neurodegenerative process originating in oligodendrocytes. Because alphaSyn represents a major component in both oligodendroglial and neuronal inclusions in MSA, some authors suggested both a primary oligodendrogliopathy and a neuronal synucleinopathy, but current biomolecular data and animal models support a crucial role of the Papp Lantos inclusions and of aberrant alphaSyn accumulation as their main constituent, causing oligodendroglial pathology, myelin disruption and, finally, neuronal degeneration in MSA. The relationship between oligodendrocytes involved by Papp-Lantos inclusions and those in degenerating neurons in the course of MSA needs further elucidation. PMID- 20309569 TI - Smoking and AMH levels in women with normal reproductive history. AB - PURPOSE: To investigate the effect of age and smoking on the AMH levels in normal cycling healthy women with normal reproductive history. MATERIALS AND METHODS: In 137 women, blood samples were taken on day 3 of a spontaneous cycle. Serum FSH, LH, E2, progesterone and AMH were measured in all blood samples. For the statistical analysis of the data, t test, Pearson's correlation and linear regression analysis were performed. RESULTS: Of 137 women (43%), 59 were smokers. Age was positively correlated with serum FSH and LH levels (r = 0.584, P < 0.001 and r = 0.330, P < 0.001, respectively) and negatively correlated with serum AMH levels (r = -0.882, P < 0.001). There were no significant differences in FSH, LH, E2, progesterone and AMH levels between smokers and non-smokers. Multiple stepwise linear regression analysis showed that in both smokers and non-smokers, age was the most significant determinant of AMH levels (r = -0.889, P < 0.001 and r = -0.944, P < 0.001, respectively), while smoking was not related to AMH levels. CONCLUSIONS: Aging significantly decreases AMH levels in women with normal cycles and normal reproductive history, while smoking does not seem to have significant effects on AMH levels. PMID- 20309570 TI - The laparoscopic-assisted vaginal approach to early endometrial cancer. AB - INTRODUCTION: For the surgical treatment of endometrial cancer laparotomy still is regarded as the gold standard. Over the past decade, the laparoscopic approach has gained equivalence in FIGO stage I carcinomas. RESULTS: Laparoscopic-assisted vaginal hysterectomy and bilateral salpingooophorectomy plus pelvic/paraaortic lymphadenectomy have shown short-term advantages such as reduced blood loss and shorter hospitalization without reducing oncological safety or outcome. This has already been confirmed by numerous smaller studies and recent randomized controlled trials with sufficient numbers of patients are being published. CONCLUSION: Further acceptance of the technique is necessary to enable every gynecological oncologist to individualize treatment by offering minimal access options. PMID- 20309571 TI - Prospective evaluation of a post-stroke epilepsy risk scale. AB - Ischemic and hemorrhagic strokes are established etiological factors for recurrent seizures. Still, only few prospective data are available to predict post-stroke epilepsy and to choose the best point in time and anticonvulsive agent for treatment. In a prospective study we evaluated 264 consecutive stroke patients and assessed their post-stroke epilepsy risk within a follow-up of 1 year. Data on ten risk items concerning the stroke localisation, persisting neurological deficit, stroke subtype, established diagnosis of vascular encephalopathy, early- and late-onset seizures were collected using a post-stroke epilepsy risk scale (PoSERS). All patients underwent brain imaging with either CT, MRI or both and 148 patients underwent electroencephalography. The overall frequency of early-onset seizures within 14 days was 4.5%, of at least one late seizure 6.4% and of epilepsy 3.8%. Chi-Square tests showed significantly higher relative frequencies of seven of the ten clinical characteristics in post-stroke epilepsy patients. The total scale showed moderate sensitivity (70%) and positive predictive value (87.5%) while specificity (99.6%) and negative predictive value (98.8%) were relatively high. The EEG showed little value in predicting post stroke epilepsy. The PoSERS appears to be a valuable tool to predict the risk for post-stroke epilepsy within the first few days after a stroke. PMID- 20309572 TI - The epidemiology of CuZn-SOD mutations in Germany: a study of 217 families. AB - We screened 217 patients from Germany (n = 213), Austria (n = 2) and Switzerland (n = 2) with a positive family history for amyotrophic lateral sclerosis (ALS) for mutations in the copper/zinc superoxide dismutase (SOD1) gene. We found that 13% of the families tested carried mutations. By analyzing inheritance, we detected a clear-cut co-segregation in 5 of the 28 families; however, in two families with an established mutation, co-segregation was absent. In Germany, the R115G mutation is comparatively frequent and exhibits a specific aggressive phenotype. The L144F mutation, which is the most prevalent mutation in the Balkan countries, and the D90A mutation which is the most frequent SOD1 mutation globally, seem to be the second most common disease-causing mutations in Germany. PMID- 20309573 TI - Idiopathic maculopathy in eyes with regressed retinopathy of prematurity. AB - BACKGROUND: To describe idiopathic maculopathy in eyes with regressed retinopathy of prematurity, which differs from cicatricial changes in retinopathy of prematurity. METHODS: SETTING: institutional. PATIENTS: patients were former preterm infants who had undergone fundus examinations for retinopathy of prematurity between December 1993 and May 2002. Posterior polar cicatricial change was excluded. The medical records of eight eyes (four patients) with photo documented idiopathic maculopathy were reviewed retrospectively. MAIN OUTCOME MEASURES: complete ophthalmologic examinations including best corrected visual acuity (BCVA), refractive error, funduscopic examination, fluorescein angiography (FAG), and optical coherence tomography (OCT). RESULTS: Maculopathy was characterized by depigmented geographic atrophy. FAG showed window defects due to atrophy of retinal pigment epithelium. OCT showed depression in the fovea with retained internal architecture. In all cases patients had retinopathy of prematurity, and all except one had been treated with laser photocoagulation. In the case without laser photocoagulation, maculopathy was observed on the first exam. In the other cases, no maculopathy was observed on the first exam, but was detected after laser photocoagulation. No patient had a family history of hereditary retinal dystrophy. In all cases, maculopathy was noted in both eyes with myopia. BCVA was variable (0.0 approximately 0.82, 0.32 +/- 0.32 logMAR). No progression was observed over the course of 8 years. CONCLUSION: Idiopathic maculopathy is a rare posterior polar change that differs from the cicatricial changes seen in retinopathy of prematurity, and is independent of prior laser photocoagulation. No progression was observed, and visual prognosis was fair. PMID- 20309574 TI - Association between macular microcirculation and soluble intercellular adhesion molecule-1 in patients with macular edema and retinal vein occlusion. AB - BACKGROUND: In patients who have macular edema secondary to retinal vein occlusion, the role of vasoactive molecules such as growth factors and the influence of molecules related to leukocyte adhesion need to be investigated further. METHODS: A prospective study was performed to investigate the relations between perifoveal capillary blood flow velocity and the vitreous levels of vascular endothelial growth factor (VEGF) and soluble intercellular adhesion molecule-1 (sICAM-1) in patients with macular edema and retinal vein occlusion. Undiluted vitreous specimens were obtained from 11 eyes of 11 patients with macular edema (nine had branch retinal vein occlusion and two had central retinal vein occlusion). VEGF and sICAM-1 levels were measured by enzyme-linked immunoabsorbent assay. Before vitreous sampling, perifoveal capillary blood flow velocity was measured by fluorescein angiography with a scanning laser ophthalmoscope and the tracing method. The relations between perifoveal capillary blood flow velocity and the vitreous levels of VEGF and sICAM-1 were investigated. RESULTS: There was a significant correlation between perifoveal capillary blood flow velocity and the vitreous level of sICAM-1 (rho = -0.7303, p = 0.03). In contrast, there was no significant association between blood flow velocity and the vitreous level of VEGF (rho = -0.1458, p = 0.67). CONCLUSIONS: The vitreous level of sICAM-1 is associated with perifoveal capillary blood flow velocity in patients who have retinal vein occlusion and macular edema. PMID- 20309575 TI - The characterization of the first anti-mouse Muc6 antibody shows an increased expression of the mucin in pancreatic tissue of Cftr-knockout mice. AB - Gel-forming mucins are large high-molecular weight secreted O-glycoproteins responsible for the gel-properties of the mucus blanket. Five orthologous gel forming mucins have been cloned in human and mouse. Among them, the mucin MUC6 has been less studied, particularly in rodents and no anti rodent-Muc6 antibody has been reported yet. In order to further study Muc6 in mice, our aims were to obtain a specific Muc6 antibody, to validate it and to test it in Cftr deficient mice. A polyclonal serum named CP4 was isolated from a rabbit immunized by a mouse Muc6 peptide. In Western blot experiments, the antibody detected a high molecular weight molecule secreted by the gastric tissue. Using immunohistochemistry, we showed that the antibody reacted strongly with deep glands of duodenum and ileum and mucous neck cells of gastric body. CP4 also recognized Muc6 protein secreted at the surface of the stomach and renal collecting tubules. The centroacinar cells of pancreatic tissue also reacted with the antibody. Cftr-/- mice showed a higher expression of Muc6 at both protein and RNA levels compared with their control Cftr+/+ littermates suggesting that as in the human disease, Muc6 may contribute to the formation of materials that block pancreatic acini and ducts in mouse models of cystic fibrosis. The rabbit anti mouse Muc6 polyclonal antibody seems highly specific to the mouse mucin and will be useful to study pancreatic pathology in cystic fibrosis. PMID- 20309576 TI - Evidence-based use of enteral nutrition in acute pancreatitis. AB - PURPOSE: A systematic review was carried out to analyze current evidence-based data on the use of enteral nutrition in the management of acute pancreatitis. METHODS: Literature search was performed on "Pubmed" and "Medline" databases to identify articles investigating the role and potential effect of enteral nutrition on the outcome of patients with acute pancreatitis. Relevant data were analyzed from the viewpoints of possible benefits and complications, route and timing of administration, and composition of nutrients. RESULTS: Thirty-two prospective randomized controlled trials and 15 meta-analyses of those were identified and included in this overview. Strong evidence suggests that enteral nutrition significantly reduces mortality rate of severe acute pancreatitis. While both nasogastric and nasojejunal feeding appear to be safe in severe pancreatitis, early low-fat oral diet is possibly beneficial in patients with mild pancreatitis. Since maintenance of the gut barrier function is one of the crucial effects of enteral nutrition, enteral feeding should be commenced within the first 24 h after hospital admission, in order to prevent early bacterial translocation. However, it seems that neither immunonoenhanced nutrients nor probiotic supplementation are able to reduce mortality further, and--therefore- cannot be recommended for patients with acute pancreatitis. CONCLUSION: Although enteral nutrition is undoubtedly a key component of the management of acute pancreatitis, the exact role of that is needed to be defined yet. In particular, conflicting data from studies on nutrient compositions will require further clarification in the future. PMID- 20309577 TI - Generation of highly pure fusions of colorectal carcinoma and antigen-presenting cells. AB - PURPOSE: The induction of potent T cell responses against tumors is the goal of tumor immunotherapy. One approach is the fusion of antigen-presenting cells (APCs) with tumor cells. Hybrid cells combine the antigenicity of tumors with the immunostimulatory capacity of APCs. However, contaminating unfused cells present in the fusion reaction may prevent the induction of antitumoral immune responses. Here, we present a simple and effective protocol to substantially elevate the purity of hybrid cells. METHODS: Colorectal tumor cell lines and CD40-activated B cells as APCs were fused using polyethylene glycol. Important parameters including cell numbers, concentrations, and handling and detection procedures were optimized. Combination of these optimized fusion conditions with both magnetic cell sorting and selective adherence delivered very pure preparations of APC/tumor cell hybrids. The T cell stimulatory capacity of these hybrids was tested using ELISpot. RESULTS: The optimization of the fusion resulted in maximal fusion efficiencies of 31.6% (n = 10, range 13.5-46.6%). Prelabeling of APCs with magnetic beads allowed for easy elimination of up to 94.3% of unfused tumor cells from the cell mixture by magnetic separation. Hybrid cell capacity to firmly adhere to plastic was then used to remove unfused B cells from the remaining cell mixture by simple washing. The obtained 85.0% pure hybrids cells readily induced antitumoral T cell responses. CONCLUSIONS: Our protocol delivers pure hybrid cell preparations with strong immunostimulatory potential. In subsequent experiments, the ability of hybrid cells to stimulate specific antitumoral T cell responses must be tested in vivo. PMID- 20309578 TI - Features of anthocyanin biosynthesis in pap1-D and wild-type Arabidopsis thaliana plants grown in different light intensity and culture media conditions. AB - The number of different anthocyanin molecules potentially produced by Arabidopsis thaliana and which anthocyanin molecule is the first product of anthocyanidin modification remain unknown. To accelerate the understanding of these questions, we investigated anthocyanin biosynthesis in rosette leaves of both pap1-D and wild-type (WT) A. thaliana plants grown in nine growth conditions, which were composed of three light intensities (low light, middle light, and high light) and three media derived from MS medium (medium-1, 2, and 3). These nine growth conditions differentially affected the levels of anthocyanins and pigmentation patterns of rosette leaves, which were closely related to the diversification levels of cyanin structures. The combined growth conditions of high light and either medium-2 or medium-1 induced the most molecular diversity of anthocyanin structures in rosette leaves of pap1-D plants. Twenty cyanin molecules, including five that were previously unknown, were characterized by HPLC-ESI-MS and HPLC-TOF MS analyses. We detected that the A. thaliana anthocyanin molecule A11 was most likely the first cyanin derived from the multiple modification steps of cyanidin. In addition, in the same growth condition, rosette leaves of pap1-D plants produced much higher levels and more diverse molecular profiling of cyanins than those of WT plants. The transcript levels of PAP1, PAL1, CHS, DFR, and ANS cDNAs were much higher in pap1-D rosette leaves than in WT ones. Furthermore, on the same agar-solidified medium, an enhancement of light intensity increased levels and molecular diversity of cyanins in both pap1-D and WT rosette leaves. In the same light intensity condition, the responses of anthocyanin levels and profiling to medium alternation were different between pap1-D and WT plants. PMID- 20309580 TI - Clinico-pathological features of breast myxoma: report of a case with histogenetic considerations. AB - We herein report the clinical, radiological, and pathological findings of a rare case of myxoma occurring in the breast parenchyma of a 75-year-old female. The tumor was incidentally detected at a mammographic screening and, ultrasonographically, presented as an ovoid mass. Histologically, an encapsulated hypocellular, myxoid tumor with low vascularization was evident. Neoplastic cells were round- to spindle/stellate-shaped and stained with vimentin and focally with calponin. We emphasize that morphology remains preeminent in the diagnosis of a breast myxoma, while immunohistochemistry may assist in ruling out other tumor entities. Differential diagnosis with all benign and malignant myxoid lesions, primarily occurring in the breast, is provided. The histogenesis of breast myxoma is unknown. The lack of expression of desmin, alpha-smooth muscle actin, CD34, CD99, CD10, bcl-2 protein, and estrogen/progesterone/androgen receptors, all markers characteristically expressed by "the benign spindle cell tumors of the mammary stroma," would suggest that breast myxoma does not fall into this tumor category and that its putative precursor mesenchymal cell resides in the interlobular stroma. PMID- 20309579 TI - Monoclonal antibodies to rhamnogalacturonan I backbone. AB - Monoclonal antibodies were raised against rhamnogalacturonan I backbone, a pectin domain, using Arabidopsis thaliana seed mucilage-derived rhamnogalacturonan I oligosaccharides--BSA conjugates. Two monoclonal antibodies, designated INRA-RU1 and INRA-RU2, selected for further characterization, were specific for the backbone of rhamnogalacturonan I, displaying no binding activity against the other pectin domains i.e. homogalacturonans, galactans or arabinans. A range of oligosaccharides was prepared by enzymatic digestion of rhamnogalacturonan I isolated from Arabidopsis thaliana seed mucilage and from sugar beet pectin, purified by low-pressure chromatography and characterized by high-performance anion-exchange chromatography and mass spectrometry. These rhamnogalacturonan I oligomers were used to characterize the binding site of the two monoclonal antibodies by competitive inhibition. Both INRA-RU1 and INRA-RU2 showed maximal binding to the [-->2)-alpha-L-rhamnosep-(1-->4)-alpha-D-galacturonic acid p-(1- >](7) structural motif but differed in their minimum binding requirement. INRA RU2 required at least two disaccharide (rhamnose-galacturonic acid) repeats for the antibody to bind, while INRA-RU1 required a minimum of six disaccharide repeats. Furthermore, the binding capacity of INRA-RU1 decreased steeply as the number of disaccharide repeats go beyond seven. Each of these antibodies reacted with hairy regions isolated from sugar beet pectin. Immunofluorescence microscopy indicated that both antibodies can be readily used to detect rhamnogalacturonan I epitopes in various cell wall samples. PMID- 20309581 TI - Anthelmintic activity of KSI-4088 against Caenorhabditis elegans. AB - Anthelmintic resistance is a serious global problem because of the worldwide spread of resistant nematodes in animals and humans. This has triggered increasing investment in research for new anthelmintics. Over the past decade, Caenorhabditis elegans has become a popular model organism for parasitic nematode research, and many examples have been published to illustrate its use. In this study, we investigated the effect of KSI-4088 on the egg hatching, larval development, and migration of the nematode worm C. elegans compared with ivermectin and levamisole (well-known anthelmintic drugs). KSI-4088 demonstrated anthelmintic activity on all assays of C. elegans. The anthelmintic activity of KSI-4088 on egg hatching and larval development showed especially strong activity, but assays showed that ivermectin and levamisole had no effects on C. elegans. In addition, KSI-4088 was capable of producing a change in the timing of the development of the worms at the L1-L3 and L4 stage. Also, we demonstrate that C. elegans L3-4 are more sensitive than adults to KSI-4088 in assay of migration. Our results indicate that KSI-4088 is an active anthelmintic compound that should be further investigated with the aim of developing a potent drug against nematodes. PMID- 20309582 TI - Osteogenic differentiation of stem cells derived from human periodontal ligaments and pulp of human exfoliated deciduous teeth. AB - Multipotent stem cells derived from periodontal ligaments (PDLSC) and pulp of human exfoliated deciduous teeth (SHED) represent promising cell sources for bone regeneration. Recent studies have demonstrated that retinoic acid (RA) and dexamethasone (Dex) induce osteogenesis of postnatal stem cells. The objective of this study was to examine the effects of RA and Dex on the proliferation and osteogenic differentiation of SHED and PDLSC and to compare the osteogenic characteristics of SHED and PDLSC under RA treatment. SHED and PDLSC were treated with serum-free medium either alone or supplemented with RA or Dex for 21 days. The proliferation of SHED and PDLSC was significantly inhibited by both RA and Dex. RA significantly upregulated gene expression and the activity of alkaline phosphatase in SHED and PDLSC. Positive Alizarin red and von Kossa staining of calcium deposition was seen on the RA-treated SHED and PDLSC after 21 days of culture. The influences of RA on the osteogenic differentiation of SHED and PDLSC were significantly stronger than with Dex. Supplementation with insulin enhanced RA-induced osteogenic differentiation of SHED. Thus, RA is an effective inducer of osteogenic differentiation of SHED and PDLSC, whereas RA treatment in combination with insulin supplementation might be a better option for inducing osteogenic differentiation. Significantly higher cell proliferation of PDLSC results in greater calcium deposition after 3-week culture, suggesting that PDLSC is a better osteogenic stem cell source. This study provides valuable information for efficiently producing osteogenically differentiated SHED or PDLSC for in vivo bone regeneration. PMID- 20309583 TI - Functional expression of alpha 7 nicotinic acetylcholine receptors in human periodontal ligament fibroblasts and rat periodontal tissues. AB - Tobacco smoking is the main risk factor associated with chronic periodontitis, but the mechanisms that underlie this relationship are largely unknown. Recent reports proposed that nicotine plays an important role in tobacco-related morbidity by acting through the nicotinic acetylcholine receptors (nAChRs) expressed by non-neuronal cells. The aim of this study was to investigate whether alpha 7 nAChR was expressed in periodontal tissues and whether it functions by regulating IL-1 beta in the process of periodontitis. In vitro, human periodontal ligament (PDL) cells were cultured with 10(-12) M of nicotine and/or 10(-9) M of alpha-bungarotoxin (alpha-Btx), a alpha 7 nAChR antagonist. The expression of alpha 7 nAChR and IL-1 beta in PDL cells and the effects of nicotine/alpha-Btx administration on their expression were explored. In vivo, an experimental periodontitis rat model was established, and the effects of nicotine/alpha-Btx administration on expression of alpha 7 nAChR and development of periodontitis were evaluated. We found that alpha 7 nAChR was present in human PDL cells and rat periodontal tissues. The expressions of alpha 7 nAChR and IL-1 beta were significantly increased by nicotine administration, whereas alpha-Btx treatment partially suppressed these effects. This study was the first to demonstrate the functional expression of alpha 7 nAChR in human PDL cells and rat periodontal tissues. Our results may be pertinent to a better understanding of the relationships among smoking, nicotine, and periodontitis. PMID- 20309584 TI - Improving intravenous fluid therapy in children with gastroenteritis. AB - Gastroenteritis is one of the most common medical conditions seen by pediatricians. The standard approach to intravenous fluid therapy for these children has been to administer a 0.9% sodium chloride (NaCl) bolus followed by a hypotonic solution ranging from 0.2-0.45% NaCl to replace the remaining deficit plus maintenance. We have questioned the safety of this approach as there have been reports of death or permanent neurologic impairment from hyponatremic encephalopathy. Hanna and Saberi (Pediatr Nephrol. doi: 10.1007/s00467-009-1428-y ) found the incidence of hospital-acquired hyponatremia (sodium < 135 mEq/L) to be 18.5% for patients presenting with isonatremic dehydration from gastroenteritis. This confirms that the current approach of using hypotonic fluids results in a high incidence of hyponatremia. Hypotonic fluids are not appropriate for rehydration in patients with gastroenteritis as it is a state of arginine vasopressin (AVP) excess due to both hemodynamic stimuli from volume depletion and non-hemodynamic stimuli such as nausea and vomiting. Free water will be retained until the volume deficit is corrected and the hemodynamic stimulus for AVP production abates. A safer and more effective approach is the administration of 0.9% NaCl in a continuous infusion following bolus therapy. 0.9% NaCl not only serves as prophylaxis against hyponatremia, but it is superior to hypotonic fluids as an extracellular volume expander and corrects the volume deficit more rapidly. PMID- 20309585 TI - Primary Sjogren syndrome that developed after IgA nephropathy. PMID- 20309586 TI - Reduction in the critical dark length for flower induction during aging in the short-day plant Pharbitis nil var. Kidachi. AB - The stress-sensitive short-day plant Pharbitis nil var. Kidachi flowers under a 16-h light and 8-h dark regime and non-stress conditions when grown for long periods of time. Such flowering was found to occur from the third week, and the floral buds were formed from the eighth node of the main stem. When young plants were grafted onto aged plants, the scions were induced to flower early. This flower induction by grafting was more effective when older plants were used as rootstocks. Grafting experiments using a single leaf as a donor revealed that younger leaves are more responsive to flower induction, suggesting that this age mediated flowering response is not induced by aging or senescence of individual leaves. Rather, the plant may obtain the ability to flower as the whole plant ages. Flowering does not occur under continuous light conditions. A night break given in the 8-h dark period inhibits flowering. These results suggest that 8-h dark conditions, which are normally considered to be long-day conditions, actually correspond to short-day conditions for this plant. The 8-h dark conditions caused early flowering more efficiently in older plants. The critical dark length determined by a single treatment was 12 h in 0-week-old plants and was reduced to 6 h in 2- and 4-week-old plants. These results suggest that the critical dark length becomes shorter when plants get older. The expression of PnFT1 and PnFT2, orthologs of the flowering gene flowering locus T, was analyzed by reverse transcription-polymerase chain reaction revealing that the expression of PnFT at the end of dark period is correlated with flowering. PMID- 20309587 TI - Strong post-pollination pre-zygotic isolation between sympatric, food-deceptive Mediterranean orchids. AB - Mediterranean orchids that grow in admixed, co-flowering populations, and frequently show hybrid progenies are interesting to use to study the nature and the strength of post-zygotic barriers. However, examination of pre- and post pollination pre-zygotic isolating mechanisms requires sympatric, co-flowering species pairs that do not produce hybrid swarms. In this study, we analyzed a contact zone between Orchis italica and O. papilionacea, in which hybrid forms have never been reported, although hybridization between members of their groups of appurtenance has been signaled. We investigated pre-pollination barriers observing the floral phenology of both species and identified pollinators by means of molecular analysis of pollinaria collected on the insects captured in the study site. Post-pollination barriers were tested performing manual crosses in order to evaluate pollen germination/pollen tube growth in vivo and fruit and seed formation. Floral phenologies of O. italica and O. papilionacea display nearly overlapping trends, and two common pollinators have been identified by molecular analysis of pollinaria. Thus, pre-pollination barriers are very weak or nonexistent. Bidirectional crosses have shown that the growth of heterospecific pollen tubes is fully blocked in stigmatic cell layers. Since no fruit formation was detected in bidirectional interspecific crosses, we assume that reproductive isolation between the examined species is fully guaranteed by post-pollination pre-zygotic mechanisms acting at stigmatic level. Such condition has been rarely described and may mask the potential action of post-zygotic mechanisms. PMID- 20309588 TI - Cetuximab-based therapy for metastatic colorectal cancer: a meta-analysis of the effect of K-ras mutations. AB - BACKGROUND: Cetuximab has a favorable effect on patients with metastatic colorectal cancer harboring wild K-ras gene. This meta-analysis was planned to quantify the benefit. METHODS: A meta-analysis of clinical studies that have used cetuximab-based therapy (CBT) for patients with known K-ras status. RESULTS: There were four randomized studies (RS) that compared CBT versus non-cetuximab control (NCC) in 2,292 patients, and six non-randomized studies (NRS) included patients received cetuximab after failure of prior chemotherapy (411 patients). Patients in RS with wild K-ras tumor gained more benefit from CBT vs. NCC. For response rate (RR), the odds ratio was 2.10 (p = 0.0002), while the hazard ratio (HR) for progression-free survival (PFS) was 0.64 (p = 0.04). On the other hand, CBT was associated with an adverse effect on RR and no effect on PFS in mutated K ras. In all patients who received CBT in RS and NRS, those with wild vs. mutated K-ras demonstrated higher RR (odds ratio 3.72; p < 0.0001). Compared with NCC in three RS, CBT showed significant overall survival (OS) advantage in patients with wild K-ras (HR = 0.68; p = 0.01). CONCLUSIONS: The significant clinical benefit of CBT concerning RR, PFS, and OS was restricted to patients with wild-type K ras. There is a need to better define potential responders to CBT. PMID- 20309589 TI - Modulation of tissue factor and thrombomodulin expression in human aortic endothelial cells incubated with high glucose. AB - Diabetes is often associated with atherothrombosis. It is unknown whether high glucose can modulate the expression of tissue factor (TF) and thrombomodulin (TM) in human aortic endothelial cells (HAECs). HAECs were treated with a lower-degree high glucose condition (LG, 11.2 mM) for 8 days and a higher-degree high glucose condition (HG, 30 mM) for 4-6 h. Methoxyphenyl tetrazolium inner salt assay, real time polymerase chain reaction, western blot, and TF activity assay were performed. In HAECs, both LG and HG conditions were nontoxic. LG caused a 74 +/- 20% decrease (P = 0.273) and HG caused a 57 +/- 5% decrease in TF mRNA expression (P = 0.001). LG caused a 53 +/- 13% decrease (P = 0.036) and HG caused a 75 +/- 10% decrease in TF protein expression (P = 0.096). TF activity was not significantly changed by LG (127 +/- 13%, P = 0.40) or HG treatments (120 +/- 42%, P = 0.70). In contrast, LG caused a 153 +/- 16% increase (P = 0.03) and HG caused a 211 +/- 20% increase in TM mRNA expression (P = 0.005). LG caused a 131 +/- 31% increase (P = 0.35) and HG caused a 140 +/- 9% increase in TM protein expression (P = 0.006). Different high glucose conditions do not provide the sufficient stress required to induce TF expression in HAECs. In contrast, high glucose conditions can induce TM expression in HAECs. PMID- 20309590 TI - Changes induced by formalin pain in central alpha1-adrenoceptor density are modulated by adenosine receptor agonists. AB - We aimed to elucidate the role of alpha(1)-adrenoceptors in adenosine analgesia in the formalin test. Formalin was injected into the hind paw of male CD-1 mice after injection of adenosine A(1) or A(2a) receptor agonists, CPA, [N(6) cyclopentyladenosine], and CGS21680 [2-p-(2-carboxyethyl)-phenylethylamino-5'-N ethylcarboxamidoadenosine hydrochloride]. In the behavioral experiment, alpha(1) adrenoceptors were blocked by an alpha(1)-adrenoceptor antagonist prazosin, 0.01 mg/kg i.p., and the time mice spent paw licking was recorded for the early (0-15 min) and late (15-60 min) phase of formalin pain. In the neurochemical experiments, mice were killed 15 or 45 min after formalin injection. The density of alpha(1)-adrenoceptors was assessed in various brain areas and in the lumbar spinal cord by [(3)H]prazosin autoradiography. Adenosine agonists produced analgesia in both phases of formalin pain, while prazosin showed a tendency to pronociceptive action in the late phase, and antagonized the effect of CGS21680. After formalin injection, alpha(1)-adrenoceptor density was elevated in some brain areas, mainly in the late phase (some contralateral amygdaloid and ipsilateral thalamic nuclei) and depressed in others (early phase in the ipsilateral spinal cord and late phase in both ipsi- and contralateral sensorimotor cortex). Elevation of alpha(1)-adrenoceptor density, which may be interpreted as a defensive response, did not develop in several cases of CPA pretreated mice. This suggests that the analgesic effect of adenosine A(1) receptor activation renders the defensive response unnecessary. The depression of alpha(1)-adrenoceptors may suggest development of hypersensitivity in a given structure, and this was antagonized by CGS21680, suggesting the role of A(2a) receptors in control of inflammatory formalin pain. PMID- 20309591 TI - Unusual electron-dense dome associates with compound plasmodesmata in the embryo suspensor of genus Sedum (Crassulaceae). AB - Plasmodesmata ensure the continuity of cytoplasm between plant cells and play an important part in the intercellular communication and signal transduction. During the development of the suspensor of both Sedum acre L. and Sedum hispanicum L., changes in the ultrastructure of plasmodesmata and adjoining cytoplasm are observed. Numerous simple plasmodesmata are present in the inner wall of the two celled embryo separating the basal cell from the apical cell. From the early globular to the torpedo stage of embryo development, the part of the wall separating the basal cell from the first layer of the chalazal suspensor cells is perforated by unusual, compound plasmodesmata. The role and the sort of transport through these plasmodesmata are discussed. PMID- 20309592 TI - Transmembrane potential measurements on plant cells using the voltage-sensitive dye ANNINE-6. AB - The charging of the plasma membrane is a necessary condition for the generation of an electric-field-induced permeability increase of the plasmalemma, which is usually explained by the creation and the growth of aqueous pores. For cells suspended in physiological buffers, the time domain of membrane charging is in the submicrosecond range. Systematic measurements using Nicotiana tabacum L. cv. Bright Yellow 2 (BY-2) protoplasts stained with the fast voltage-sensitive fluorescence dye ANNINE-6 have been performed using a pulsed laser fluorescence microscopy setup with a time resolution of 5 ns. A clear saturation of the membrane voltage could be measured, caused by a strong membrane permeability increase, commonly explained by enhanced pore formation, which prevents further membrane charging by external electric field exposure. The field strength dependence of the protoplast's transmembrane potential V (M) shows strong asymmetric saturation characteristics due to the high resting potential of the plants plasmalemma. At the pole of the hyperpolarized hemisphere of the cell, saturation starts at an external field strength of 0.3 kV/cm, resulting in a measured transmembrane voltage shift of ?V(M) = -150 mV, while on the cathodic (depolarized) cell pole, the threshold for enhanced pore formation is reached at a field strength of approximately 1.0 kV/cm and ?V(M) = 450 mV, respectively. From this asymmetry of the measured maximum membrane voltage shifts, the resting potential of BY-2 protoplasts at the given experimental conditions can be determined to V(R) = -150 mV. Consequently, a strong membrane permeability increase occurs when the membrane voltage diverges |V(M)| = 300 mV from the resting potential of the protoplast. The largest membrane voltage change at a given external electric field occurs at the cell poles. The azimuthal dependence of the transmembrane potential, measured in angular intervals of 10 degrees along the circumference of the cell, shows a flattening and a slight decrease at higher fields at the pole region due to enhanced pore formation. Additionally, at the hyperpolarized cell pole, a polarization reversal could be observed at an external field range around 1.0 kV/cm. This behavior might be attributed to a fast charge transfer through the membrane at the hyperpolarized pole, e.g., by voltage-gated channels. PMID- 20309593 TI - Distribution of methionine between cells and incubation medium in suspension of rat hepatocytes. AB - Methionine is an essential amino acid involved in many significant intracellular processes. Aberrations in methionine metabolism are associated with a number of complex pathologies. Liver plays a key role in regulation of blood methionine level. Investigation of methionine distribution between hepatocytes and medium is crucial for understanding the mechanisms of this regulation. For the first time, we analyzed the distribution of methionine between hepatocytes and incubation medium using direct measurements of methionine concentrations. Our results revealed a fast and reversible transport of methionine through the cell membrane that provides almost uniform distribution of methionine between hepatocytes and incubation medium. The steady-state ratio between intracellular and extracellular methionine concentrations was established within a few minutes. This ratio was found to be 1.06+/-0.38, 0.89+/-0.26, 0.67+/-0.16 and 0.82+/-0.06 at methionine concentrations in the medium of 64+/-19, 152+/-39, 413+/-55, and 1,204+/-104 MUmol/L, respectively. The fast and uniform distribution of methionine between hepatocytes and extracellular compartments provides a possibility for effective regulation of blood methionine levels due to methionine metabolism in hepatocytes. PMID- 20309594 TI - Development and behaviour of 5-year-old very low birthweight infants. AB - The place and time of birth influence the mortality of premature infants. We studied the effect of prematurity, time of birth, birth hospital level and district on the development and behaviour in a national cohort of 5-year-old Finnish very low birthweight infants (VLBWI). All surviving VLBWI (gestational age <32 weeks or birthweight Freundlich (two-parameter) > Langmuir (two-parameter) > Khan (three parameter) > Fritz-Schluender (four-parameter). The thermodynamic parameters such as DeltaG (0), DeltaH (0) and DeltaS (0) have been determined, which indicates the sorption of Ni(II) onto L. variegata was spontaneous and endothermic in nature. PMID- 20309611 TI - The reliability of cause-of-death coding in The Netherlands. AB - Cause-of-death statistics are a major source of information for epidemiological research or policy decisions. Information on the reliability of these statistics is important for interpreting trends in time or differences between populations. Variations in coding the underlying cause of death could hinder the attribution of observed differences to determinants of health. Therefore we studied the reliability of cause-of-death statistics in The Netherlands. We performed a double coding study. Death certificates from the month of May 2005 were coded again in 2007. Each death certificate was coded manually by four coders. Reliability was measured by calculating agreement between coders (intercoder agreement) and by calculating the consistency of each individual coder in time (intracoder agreement). Our analysis covered an amount of 10,833 death certificates. The intercoder agreement of four coders on the underlying cause of death was 78%. In 2.2% of the cases coders agreed on a change of the code assigned in 2005. The (mean) intracoder agreement of four coders was 89%. Agreement was associated with the specificity of the ICD-10 code (chapter, three digits, four digits), the age of the deceased, the number of coders and the number of diseases reported on the death certificate. The reliability of cause-of death statistics turned out to be high (>90%) for major causes of death such as cancers and acute myocardial infarction. For chronic diseases, such as diabetes and renal insufficiency, reliability was low (<70%). The reliability of cause-of death statistics varies by ICD-10 code/chapter. A statistical office should provide coders with (additional) rules for coding diseases with a low reliability and evaluate these rules regularly. Users of cause-of-death statistics should exercise caution when interpreting causes of death with a low reliability. Studies of reliability should take into account the number of coders involved and the number of codes on a death certificate. PMID- 20309612 TI - Effect of inter-reader variability on outcomes in studies using carotid intima media thickness quantified by carotid ultrasonography. AB - Systematic differences between readers or equipment in imaging studies are not uncommon; failure to account for such differences when using Carotid Ultrasonography may introduce bias into associations between carotid intima media thickness (cIMT) and outcomes. We demonstrate the impact of this source of systematic measurement error (SME) using data on 5,521 participants from the Multi-Ethnic Study of Atherosclerosis (MESA) and 661 participants from the Study of Fat Redistribution and Metabolic Change in HIV Infection (FRAM). Participants were between 37 and 78 years old. Two outcomes were considered: (1) the effect of HIV infection on cIMT (between study) and (2) the association of cIMT with cardiovascular events (within study). All estimates were adjusted for demographics (age, gender, and ethnicity) and for traditional cardiovascular disease risk factors (smoking, blood pressure, diabetes and cholesterol). When comparing the FRAM and MESA cohorts to estimate the association of HIV infection on common cIMT, accounting for machine and reader variability (between study variability) reduced the difference associated with HIV infection from +0.080 mm (95% Confidence Interval (CI):0.065-0.095) to +0.037 mm (95% CI:0.003 to 0.072) while internal cIMT declined from +0.254 mm (95% CI:0.205-0.303) to +0.192 mm (95% CI:0.076-0.308). Attenuation of the association between cIMT and cardiovascular endpoints occurred when within study reader variability was not accounted for. The effect of SME due to use of multiple readers or machines is most important when comparisons are made between two different study populations. Within-cohort measurement error dilutes the association with events. PMID- 20309613 TI - Trends in advanced glycation end products research in diabetes mellitus and its complications. AB - Advanced glycation end-products (AGEs) are heterogeneous groups of compounds that result from the non-enzymatic reaction of reducing sugars with free amino groups of biological molecules such as proteins, lipids, and nucleic acids. A large number of studies have been focused on AGEs metabolism, analysis, treatments, and their implications in the pathogenesis of diseases, especially in diabetes mellitus. Here, we review recent advances in the understanding of pathological complications caused by the production of AGEs. We provide an overview of the most important issues published within this area in last years; we also present the number of scientific papers related to AGEs available since 1950 until 2008 in the most important fields including metabolism, physiology, and pharmacology, thus as analytical methods for AGE detection and quantification and studies carried out in human body fluids. Data were collected from ovidSP. PMID- 20309614 TI - Daidzein effect on hormone refractory prostate cancer in vitro and in vivo compared to genistein and soy extract: potentiation of radiotherapy. AB - PURPOSE: Genistein, the major bioactive isoflavone of soybeans, acts as a radiosensitizer for prostate cancer (PCa) both in vitro and in vivo. However, pure genistein promoted increased metastasis to lymph nodes. A mixture of soy isoflavones (genistein, daidzein, glycitein) did not cause increased metastasis, but potentiated radiotherapy. We tested whether daidzein could negate genistein induced metastasis. METHODS: Mice bearing PC-3 prostate tumors were treated with daidzein, genistein or both, and with tumor irradiation. Primary tumors and metastases were evaluated. The effects of each isoflavone and soy were compared in vitro using PC-3 (AR-) and C4-2B (AR+) androgen-independent PCa cell lines. RESULTS: Daidzein did not increase metastasis to lymph nodes and acted as a radiosensitizer for prostate tumors. Daidzein inhibited cell growth and enhanced radiation in vitro but at doses higher than genistein or soy. Daidzein caused milder effects on inhibition of expression and/or activities of APE1/Ref-1, HIF 1alpha and NF-kappaB in PC-3 and C4-2B cells. CONCLUSIONS: Daidzein could be the component of soy that protects against genistein-induced metastasis. Daidzein inhibited cell growth and synergized with radiation, affecting APE1/Ref-1, NF kappaB and HIF-1alpha, but at lower levels than genistein and soy, in AR+ and AR- PCa cells, suggesting it is an AR-independent mechanism. PMID- 20309616 TI - The development and mechanism studies of cationic chitosan-modified biodegradable PLGA nanoparticles for efficient siRNA drug delivery. AB - PURPOSE: In order to improve siRNA delivery for possible clinical applications, we developed biodegradable chitosan-modified poly(D,L-lactide-co-glycolide) (CHT PLGA) nanoparticles with positive surface charge, high siRNA loading, high transfection efficiency and low toxicity. METHODS: CHT-PLGA nanoparticles were prepared, and siRNA was loaded by emulsion evaporation method with poly(vinyl alcohol) (PVA) as emulsifier. siRNA loading efficiency, particle size, and Zeta potential of nanoparticles were measured. Gel retardation and protection assays were conducted to determine the loading and binding of siRNA in the formulation. Cell transfection was performed to study in vitro siRNA silencing efficiency. XTT assay was used to evaluate the cytotoxicity. RESULTS: It was found that the nanoparticle diameter and positive Zeta potential increase as the chitosan coating concentration increases. CHT-PLGA nanoparticles showed excellent siRNA binding ability and effective protection of oligos from RNase degradation. siRNA loaded nanoparticles were successfully delivered into the HEK 293 T cell line, and the silencing of green fluorescence protein (GFP) expression was observed using fluorescent microscopy and flow cytometry. In addition, the cytotoxicity assay revealed that CHT-PLGA nanoparticles had relatively low cytotoxicity. CONCLUSION: This study suggests that biodegradable cationic CHT-PLGA nanoparticles possess great potential for efficient and safer siRNA delivery in future clinical applications. PMID- 20309617 TI - Subterranean herbivore-induced volatiles released by citrus roots upon feeding by Diaprepes abbreviatus recruit entomopathogenic nematodes. AB - Herbivore-induced volatile emissions benefit plant hosts by recruiting natural enemies of herbivorous insects. Such tritrophic interactions have been examined thoroughly in the above-ground terrestrial environment. Recently, similar signals have also been described in the subterranean environment, which may be of equal importance for indirect plant defense. The larvae of the root weevil, Diaprepes abbreviates, are a serious pest of citrus. Infestations can be controlled by the use of entomopathogenic nematodes, yet the interactions between the plant, insect and nematode are poorly understood and remain unpredictable. In bioassays that used a root zone six-arm olfactometer, citrus roots ('Swingle citrumelo' rootstock) recruited significantly more entomopathogenic nematodes (Steinernema diaprepesi) when infested with root weevil larvae than non-infested roots. Infested plants were more attractive to nematodes than larvae alone. Roots damaged by weevil larvae attracted more nematodes than mechanically damaged roots and sand controls. By dynamic in situ collection and GC-MS analysis of volatiles from soil, we determined that four major terpene compounds were produced by infested plant roots that were not found in samples from non-infested roots or soil that contained only larvae. Solvent extracts of weevil-infested roots attracted more nematodes than extracts of non-infested roots in a two choice sand column bioassay. These findings suggest that Swingle citrus roots release induced volatiles as an indirect defense in response to herbivore feeding, and that some of these induced volatiles function as attractants for entomopathogenic nematodes. PMID- 20309618 TI - Species by environment interactions affect pyrrolizidine alkaloid expression in Senecio jacobaea, Senecio aquaticus, and their hybrids. AB - We examined the effects of water and nutrient availability on the expression of the defense pyrrolizidine alkaloids (PAs) in Senecio jacobaea and S. aquaticus. Senecio jacobaea, and S. aquaticus are adapted to different natural habitats, characterized by differing abiotic conditions and different selection pressures from natural enemies. We tested if PA concentration and diversity are plastic over a range of water and nutrient treatments, and also whether such plasticity is dependent on plant species. We also tested the hypothesis that hybridization may contribute to PA diversity within plants, by comparing PA expression in parental species to that in artificially generated F(1) hybrids, and also in later generation natural hybrids between S. jacobaea and S. aquaticus. We showed that total PA concentration in roots and shoots is not dependent on species, but that species determines the pattern of PA diversification. Pyrrolizidine alkaloid diversity and concentration are both dependent on environmental factors. Hybrids produce a putatively novel PA, and this PA is conserved in natural hybrids, that are backcrossed to S. jacobaea. Natural hybrids that are backcrossed several times to S. jacobaea are with regard to PA diversity significantly different from S. jacobaea but not from S. aquaticus, while F(1) hybrids are in all cases more similar to S. jacobaea. These results collectively suggest that PA diversity is under the influence of natural selection. PMID- 20309619 TI - Couples' attributions for work function changes in prodromal Huntington disease. AB - People who have tested positive for the expanded Huntington disease (HD) gene who are not yet diagnosed (pre-HD) and their companions report subtle changes in ability of people with pre-HD to do their jobs. However, it is not known whether they attribute these changes to HD. Semi-structured telephone interviews were analyzed from seven persons with pre-HD at different estimated points from diagnosis and six companions. Data were analyzed using qualitative analysis methods. Participants made attributions related to health, work, and temperament. Only one participant attributed a change to HD. The process of forming attributions was demonstrated through symptom monitoring and comparison of participants with pre-HD to others with and without HD. Participants also expressed uncertainty regarding how to make attributions. Attributions influence coping procedures, including whether to seek and accept medical treatment. In persons with prodromal HD the relationship between attributions and use of coping strategies for symptoms that interfere with job functioning is unknown. PMID- 20309620 TI - Modeling shifts in the rate and pattern of subthalamopallidal network activity during deep brain stimulation. AB - Deep brain stimulation (DBS) of the subthlamic nucleus (STN) represents an effective treatment for medically refractory Parkinson's disease; however, understanding of its effects on basal ganglia network activity remains limited. We constructed a computational model of the subthalamopallidal network, trained it to fit in vivo recordings from parkinsonian monkeys, and evaluated its response to STN DBS. The network model was created with synaptically connected single compartment biophysical models of STN and pallidal neurons, and stochastically defined inputs driven by cortical beta rhythms. A least mean square error training algorithm was developed to parameterize network connections and minimize error when compared to experimental spike and burst rates in the parkinsonian condition. The output of the trained network was then compared to experimental data not used in the training process. We found that reducing the influence of the cortical beta input on the model generated activity that agreed well with recordings from normal monkeys. Further, during STN DBS in the parkinsonian condition the simulations reproduced the reduction in GPi bursting found in existing experimental data. The model also provided the opportunity to greatly expand analysis of GPi bursting activity, generating three major predictions. First, its reduction was proportional to the volume of STN activated by DBS. Second, GPi bursting decreased in a stimulation frequency dependent manner, saturating at values consistent with clinically therapeutic DBS. And third, ablating STN neurons, reported to generate similar therapeutic outcomes as STN DBS, also reduced GPi bursting. Our theoretical analysis of stimulation induced network activity suggests that regularization of GPi firing is dependent on the volume of STN tissue activated and a threshold level of burst reduction may be necessary for therapeutic effect. PMID- 20309621 TI - The heavy burden of psychiatric comorbidity in youth with autism spectrum disorders: a large comparative study of a psychiatrically referred population. AB - The objective of the study was to systematically examine patterns of psychiatric comorbidity in referred youth with autism spectrum disorders (ASD) including autistic disorder and pervasive developmental disorder not otherwise specified. Consecutively referred children and adolescents to a pediatric psychopharmacology program were assessed with structured diagnostic interview and measures of psychosocial functioning. Comparisons were made between those youth satisfying diagnostic criteria for ASD and age and sex matched youth without ASD referred to the same clinical program. 9.3% (217/2323) of the referred youth (age range: 3-17 years) met DSM-III-R criteria for ASD. ASD youth suffered from significantly higher number of comorbid disorders than comparisons (6.4 +/- 2.7 vs. 5.2 +/- 2.9; p < 0.001). Ninety-five percent of the youth with ASD had three or more comorbid psychiatric disorders and 74% had five or more comorbid disorders. ASD youth were also more functionally impaired and required extra-assistance in school and therapeutic interventions at higher rates than age and sex matched non ASD referred youth. Youth with ASD have high levels of psychiatric comorbidity and dysfunction comparable to the referred population of youth without ASD. These findings emphasize the heavy burden of psychiatric comorbidity afflicting youth with ASD and may be important targets for intervention. PMID- 20309622 TI - A preliminary study: the anti-proliferation effect of salidroside on different human cancer cell lines. AB - Salidroside (p-hydroxyphenethyl-beta-d-glucoside), which is present in all species of the genus Rhodiola, has been reported to have a broad spectrum of pharmacological properties. The present study, for the first time, focused on evaluating the effects of the purified salidroside on the proliferation of various human cancer cell lines derived from different tissues, and further investigating its possible molecular mechanisms. Cell viability assay and [(3)H] thymidine incorporation were used to evaluate the cytotoxic effects of salidroside on cancer cell lines, and flow cytometry analyzed the change of cell cycle distribution induced by salidroside. Western immunoblotting further studied the expression changes of cyclins (cyclin D1 and cyclin B1), cyclin-dependent kinases (CDK4 and Cdc2), and cyclin-dependent kinase inhibitors (p21(Cip1) and p27(Kip1)). The results showed that salidroside inhibited the growth of various human cancer cell lines in concentration- and time-dependent manners, and the sensitivity to salidroside was different in those cancer cell lines. Salidroside could cause G1-phase or G2-phase arrest in different cancer cell lines, meanwhile, salidroside resulted in a decrease of CDK4, cyclin D1, cyclin B1 and Cdc2, and upregulated the levels of p27(Kip1) and p21(Cip1). Taken together, salidroside could inhibit the growth of cancer cells by modulating CDK4-cyclin D1 pathway for G1-phase arrest and/or modulating the Cdc2-cyclin B1 pathway for G2 phase arrest. PMID- 20309623 TI - Toward the integration of education and mental health in schools. AB - Education and mental health integration will be advanced when the goal of mental health includes effective schooling and the goal of effective schools includes the healthy functioning of students. To build a solid foundation for this reciprocal agenda, especially within the zeitgeist of recent educational reforms, a change in the fundamental framework within which school mental health is conceptualized is needed. This change involves acknowledging a new set of priorities, which include: the use of naturalistic resources within schools to implement and sustain effective supports for students' learning and emotional/behavioral health; inclusion of integrated models to enhance learning and promote health; attention to improving outcomes for all students, including those with serious emotional/behavioral needs; and strengthening the active involvement of parents. A strong research agenda to support these new priorities is essential. PMID- 20309624 TI - Inconsistent self-report of delinquency by adolescents and young adults with ADHD. AB - The purpose of the current study was to test the ability of adolescents and young adults with childhood ADHD to reliably self-report delinquency history. Data were examined from the Pittsburgh ADHD Longitudinal Study (PALS), a follow-up study of children diagnosed with ADHD between 1987 and 1996. Self-report of lifetime delinquency history was compared to concurrent parent-report and to self-report 1 year later. Participants included 313 male probands and 209 demographically similar comparison individuals without ADHD. Results indicated that adolescents and young adults with childhood ADHD were more likely than comparison participants to fail to report delinquent acts reported by a parent and to recant acts they endorsed 1 year earlier. This trend was most apparent for acts of mild to moderate severity. After controlling for several covariates, current ADHD symptom severity and parent-report of the participant's tendency to lie predicted reporting fewer delinquent acts than one's parent. Current ADHD symptom severity also predicted more recanting of previously endorsed acts. Based on these findings, several recommendations are made for the assessment of delinquency history in adolescents and young adults with childhood ADHD. PMID- 20309625 TI - Familism, parent-adolescent conflict, self-esteem, internalizing behaviors and suicide attempts among adolescent Latinas. AB - Adolescent Latinas continue to report higher levels of suicide attempts than their African-American and White peers. The phenomenon is still not understood and is theorized to be the result of the confluence of many cultural, familial, and individual level factors. In Latino cultures, belief in the importance of the family, the value known as familism, appears to protect youth's emotional and behavioral health, but parent-adolescent conflict has been found to be a risk factor for suicide attempts. The role of familism in relation to parent adolescent conflict, self-esteem, internalizing behaviors, and suicide attempts has not been studied extensively. To address this question, we interviewed 226 adolescent Latinas, 50% of whom had histories of suicide attempts. Using path analysis, familism as a cultural asset was associated with lower levels of parent adolescent conflict, but higher levels of internalizing behaviors, while self esteem and internalizing behaviors mediated the relationship between parent adolescent conflict and suicide attempts. Our findings point to the importance of family involvement in culturally competent suicide prevention and intervention programs. Reducing parent-daughter conflict and fostering closer family ties has the added effect of improving self-esteem and shrinking the likelihood of suicide attempts. PMID- 20309626 TI - Transforming growth factor-beta1 polymorphisms and breast cancer risk: a meta analysis based on 27 case-control studies. AB - The association between transforming growth factor-beta1 (TGF-beta1) gene polymorphisms and breast cancer risk has been widely reported, but results were somewhat controversial and underpowered. To derive a more precise estimation of the relationship between TGF-beta1 polymorphisms and breast cancer risk, we conducted a meta-analysis of all available case-control studies relating the T869C and/or C-509T polymorphisms of the TGF-beta1 gene to the risk of developing breast cancer. Eligible articles were identified by search of databases including MEDLINE, PubMed, Web of Science, EMBASE, and Chinese Biomedical Literature database (CBM) for the period up to March 2010. Finally, a total of 17 articles involving 27 case-control studies were identified, 25 with 20,022 cases and 24,423 controls for T869C polymorphism and eight with 10,633 cases and 13,648 controls for C-509T polymorphism. The pooled ORs were performed for the allele contrasts, additive genetic model, dominant genetic model and recessive genetic model, respectively. Subgroup analysis was also performed by ethnicity for T869C polymorphism. With respect to T869C polymorphism, no association was found in overall analysis (C vs. T: OR = 1.033, 95% CI = 0.996-1.072). In the subgroup analysis by ethnicity, significantly increased risk was found in Caucasian population (C vs. T: OR = 1.051, 95% CI = 1.018-1.085; CC vs. TT + TC: OR = 1.083, 95% CI = 1.019-1.151), but not in Asian population (C vs. T: OR = 1.054, 95% CI = 0.983-1.130). With respect to C-509T polymorphism, no significant association with breast cancer risk was demonstrated in overall analysis (T vs. C: OR = 0.986, 95% CI = 0.936-1.039). It can be concluded that potentially functional TGF-Beta1 T869C polymorphism may play a low penetrance role in breast cancer susceptibility in an ethnicity-specific manner. PMID- 20309627 TI - Evaluation of established breast cancer risk factors as modifiers of BRCA1 or BRCA2: a multi-center case-only analysis. AB - The incomplete penetrance of mutations in BRCA1 and BRCA2 suggests that some combination of environmental and genetic factors modifies the risk of breast cancer in mutation carriers. This study sought to identify possible interactions between established breast cancer risk factors and BRCA1 or BRCA2 mutations using a case-only study design. Breast cancer cases that had been tested for BRCA1 and BRCA2 mutations were identified from 11 collaborating centers. Comparisons of reproductive and lifestyle risk factors were made between women with breast cancer who were positive for BRCA1 mutations (n = 283), BRCA2 mutations (n = 204), or negative for both BRCA1 and BRCA2 mutations (n = 894). Interaction risk ratios (IRRs) were calculated using multinominal logistic regression models. Compared with non-carriers, statistically significant IRRs were observed for later age at menarche among BRCA2 mutation carriers, for a greater number of pregnancies among both BRCA1 and BRCA2 mutation carriers, and for alcohol use among BRCA1 mutation carriers. Our data suggest that the risk for breast cancer among BRCA1 or BRCA2 carriers may be modified by reproductive characteristics and alcohol use. However, our results should be interpreted cautiously given the overall inconsistency in the epidemiologic literature on modifiers of BRCA1 and BRCA2. PMID- 20309629 TI - Biochemical composition of juvenile cultured vs. wild silver pomfret, Pampus argenteus: determining the diet for cultured fish. AB - We evaluated the biochemical composition of juvenile cultured and wild silver pomfret Pampus argenteus. Cultured silver pomfret (SF) had significantly (P<0.05) lower crude protein content and higher crude lipid content than wild SF. Concentrations of almost all amino acids, except glycine and arginine, were significantly higher (P<0.05) in wild SF compared to cultured SF. Further, wild SF had a significantly (P<0.05) higher concentration of total amino acids (TAA), essential amino acids (EAA), and a higher essential amino acid index (EAAI) than cultured SF. Saturated fatty acids (SFA) in cultured SF were significantly higher than in wild SF. However, the content of poly-unsaturated fatty acids (PUFA) and n-3 fatty acids in wild SF was significantly higher than in cultured SF. Mono unsaturated fatty acids (MUFA) in cultured and wild SF were not significantly different. Fatty acids C16:0 and C18:1 were the principal fatty acids of the SFAs and MUFAs, respectively, in both cultured and wild SF. The results will be useful for determining the dietary requirements for culture of SF. PMID- 20309628 TI - Manganese superoxide dismutase polymorphism, treatment-related toxicity and disease-free survival in SWOG 8897 clinical trial for breast cancer. AB - To date, the few studies of associations between a functional polymorphism in the oxidative stress-related gene manganese superoxide dismutase (SOD2) and breast cancer survival have been inconsistent. In a homogeneous patient population from a large cooperative group trial Southwest Oncology Group (SWOG) 8897, we evaluated this polymorphism in relation to both treatment-related toxicity and disease-free survival (DFS). Among 458 women who received cyclophosphamide containing adjuvant chemotherapy, those with variant C alleles, related to higher antioxidant activity, experienced less grade 3-4 neutropenia (OR = 0.52, 95% CI = 0.29-0.92) but had worse DFS (HR = 1.59, 95% CI = 0.99-2.55) than women with TT genotypes. No associations were observed among 874 women who were followed without adjuvant therapy. Our results are consistent with the hypothesis that women with higher SOD2 antioxidant activity may experience less treatment-related toxicity but shorter time to disease recurrence or death after breast cancer adjuvant chemotherapy, supporting the modifying effects of oxidative stress related enzymes on cancer treatment toxicity and efficacy. PMID- 20309630 TI - Antioxidant system breakdown in brain of feral golden grey mullet (Liza aurata) as an effect of mercury exposure. AB - Although brain has been recognized as a primary target for mercury toxicity in mammals, the effects of this metal in fish brain are scarcely described. Thus, the main objective of this study was to assess the mercury threat to feral fish (Liza aurata) by estimating the antioxidant defenses and peroxidative damage in brain, keeping in mind the association with mercury accumulation. Sampling was carried out in an estuarine area historically affected by discharges from a chlor alkali industry-Laranjo Basin (Ria de Aveiro, Portugal). Total mercury (T-Hg) in brain increased towards the contamination source, clearly indicating mercury exposure. An overall antioxidant depletion was verified in brain of fish collected at the mercury-contaminated stations, since total glutathione content and the studied antioxidant enzymes (catalase-CAT, glutathione peroxidase-GPx, glutathione-S-transferase-GST and glutathione reductase-GR) significantly decreased. In addition, this breakdown of the redox-defense system was significantly correlated with the accumulated T-Hg levels. Unexpectedly, fish exhibited unaltered lipid peroxidation levels, pointing out a higher propensity of mercury to inhibit enzymes than to oxidatively damage lipids in the brain. Nevertheless, an increased susceptibility of the fish's brain was identified, leaving the organ more vulnerable to oxidative stress-related challenges. Overall, the current findings provide information to better understand mechanisms of mercury neurotoxicity in fish. PMID- 20309631 TI - Product-limit estimators of the gap time distribution of a renewal process under different sampling patterns. AB - Nonparametric estimation of the gap time distribution in a simple renewal process may be considered a problem in survival analysis under particular sampling frames corresponding to how the renewal process is observed. This note describes several such situations where simple product limit estimators, though inefficient, may still be useful. PMID- 20309632 TI - Cost-effective gene transfection by DNA compaction at pH 4.0 using acidified, long shelf-life polyethylenimine. AB - Introduction of genetic material into cells is an essential prerequisite for current research in molecular cell biology. Although transfection with commercially available reagents results in excellent gene expression, their high costs are obstacles to experimentation with a large number or large scales of transfection. The cationic polymer linear-polyethylenimine (MW 25,000) (PEI), one of the most cost-effective vehicles, facilitates DNA compaction by polyplex formation, which leads to efficient delivery of DNA into cells by endocytosis. However, the use of PEI is still limited because of substantial cytotoxicity and intolerable deterioration in transfection efficiency by its low stability. Here, we show that acidification of PEI is important for its transfection activity. Dissolving PEI powder in 0.2N HCl confers a long shelf-life for PEI storage at 4 and -80 degrees C, and the polyplex formation of plasmid DNA with PEI is optimized in lactate-buffered saline at pH 4.0. Furthermore, changing the culture medium at 8-12 h posttransfection can minimize the cytotoxicity of PEI without sacrificing the high transfection efficiency comparable to that of commercial reagents. The cost per test using acidified PEI is drastically reduced to approximately 1:10,000, compared with commercial reagents. Thus, we conclude that acidification of PEI satisfactorily accomplishes cost-effective, high-efficiency transfection. PMID- 20309633 TI - Positive and negative reinforcement underlying risk behavior in early adolescents. AB - The goal of the current study was to examine the combined influence of positive reinforcement processes using a behavioral task measuring risk taking propensity (RTP) and negative reinforcement processes using a behavioral task measuring deficits in distress tolerance (DT) on a range of risk taking behaviors among early adolescents. Participants included a community sample of 230 early adolescents (aged 9-13) who completed two behavioral tasks assessing reinforcement processes as well as reported on past year risk behavior involvement as assessed by items from the Youth Risk Behavior Surveillance System at a baseline and a 1-year follow-up assessment. Data indicated that at the Wave 2 assessment, RTP was positively related to number of risk-taking behaviors in the past year but only for those with low DT, with this finding persisting after controlling for the significant influence of male gender and higher sensation seeking. Results of the present study highlight the importance of considering both positive and negative reinforcement processes in combination when investigating vulnerability factors for early risk behavior engagement in youth. PMID- 20309635 TI - Heart involvement in systemic sclerosis: present but not evident. PMID- 20309636 TI - Strategic costs and preferences revelation in the allocation of resources for health care. AB - This article examines the resources allocation process in the internal market for health care in an environment characterised by asymmetry of information. We analyse the strategic behaviour of the provider and show how, by misreporting its cost function and reservation utility, it might shift the allocation of resources away from the purchaser's objectives. Although the fundamental importance of equity, efficiency and risk aversion considerations which have been the traditional focus of the literature on allocation of resources should not be denied, this paper shows that contracts and internal markets are not neutral instruments and more research should be devoted to studying their effects. PMID- 20309637 TI - IL-29 and IFN-alpha regulate the expression of MxA, 2',5'-OAS and PKR genes in association with the activation of Raf-MEK-ERK and PI3K-AKT signal pathways in HepG2.2.15 cells. AB - Interferons (IFNs) can activate the PI3K-AKT and Raf-MEK-ERK signal pathways and induce antiviral proteins (MxA, 2',5'-OAS and PKR) expression in specific cell lines. However, the relationship between those antiviral proteins expression and signal pathways remains unknown at present. Thus our experiments were designed to determine the exact relationship in HepG2.2.15 cell line. The results demonstrated that IFN-alpha and IL-29 were both able to activate PI3K-AKT and Raf MEK-ERK signal pathways, and IFN-alpha up-regulated the expression of MxA, 2',5' OAS and PKR whereas IL-29 increased mRNA expression of MxA and 2',5'-OAS and had no influence on PKR. Furthermore, MxA, 2',5'-OAS and PKR expression were down regulated while PI3K-AKT signal pathway was blocked by LY294002. And MxA was up regulated after Raf-MEK-ERK signal pathway being blocked by PD98059. These findings indicate that the expression of MxA, 2',5'-OAS and PKR are up-regulate by PI3K-AKT signal pathway, and Raf-MEK-ERK signal pathway has a negative regulatory effect on the expression of MxA and no significant effect on 2',5'-OAS and PKR. PMID- 20309638 TI - The SF-36 component summary scales and the daytime diurnal cortisol profile. AB - PURPOSE: Higher daytime cortisol output has been associated with higher levels of perceived stress and worse mental and physical health outcomes. Hypothalamic pituitary-adrenal (HPA) axis dysregulation, such as elevated secretion of daytime cortisol, occurs in many mental and physical illnesses. However, the nature of the association between functional health status and daytime cortisol production has not been established. METHODS: Healthy adult volunteers (n=68, 45 females) provided saliva samples 3, 6, 9 and 12 h after waking, for two consecutive days, in everyday settings. Bivariate correlations between log salivary cortisol concentrations were calculated, and the SF-36 component summary scores were calculated. Latent growth curve modeling was used to model the daytime profile and adjust for covariates (age, sex and waking time). RESULTS: Higher PCS scores were not associated with cortisol three hours after waking (cortisol intercept), or the diurnal decline (cortisol slope). Higher MCS scores were correlated with faster cortisol decline across the day (r=-.31, P<.01) but not with cortisol intercepts. In a latent growth curve model adjusting for age, sex and waking time, the association was no longer statistically significant. CONCLUSIONS: Large scale epidemiological studies involving salivary cortisol would benefit from measuring SF-36 component summary scores. Cortisol intercepts and slopes may be differentially related to the PCS and MCS, although greater statistical power is needed to test this hypothesis more fully. Associations between daytime cortisol and the PCS or MCS could reflect the regulatory competence of bodily systems, common causes or unmeasured confounding factors. PMID- 20309639 TI - Risk of varices bleeding after spleen-preserving distal pancreatectomy with excision of splenic artery and vein. AB - BACKGROUND: Spleen-preserving distal pancreatectomy with excision of splenic vessels (SPDP-ESV) has been widely adopted because of its simplicity. However, this simplified technique may lead to gastric varices and bleeding. METHODS: For better understanding of the hemodynamic changes and risk of gastric variceal bleeding, we instituted a prospective study to perform serial follow-up contrast abdominal computed tomography (CT) and endoscopy for patients after SPDP-ESV. RESULTS: There were 37 patients, with a mean follow-up period of 45.3 months (range 23-59 months), included in the analysis. Of the 37 patients studied, 11 (29.7%) had perigastric varices, 12 (32.4%) had splenomegaly, and 3 (8.1%) had gastric submucosal varices on follow-up CT performed 6 months after surgery. Endoscopy also showed gastric varices in three patients with gastric submucosal varices on CT scan. CT performed 18 months after surgery showed no progression of splenomegaly or gastric submucosal varices. Follow-up endoscopies also showed three gastric varices detected on endoscopy at 6 months to be stationary. CONCLUSIONS: Based on serial CT and endoscopic examinations, the first postoperative months will show who is at risk of gastric variceal bleeding. PMID- 20309640 TI - Adherence to the National Quality Forum (NQF) breast cancer measures within cancer clinical trials: a review from ACOSOG Z0010. AB - BACKGROUND: In 2007, the National Quality Forum (NQF) released four performance measures for the treatment of breast cancer. We proposed to study the degree of adherence with these measures among participating institutions in a multi institutional trial. METHODS: American College of Surgeons Oncology Group (ACOSOG) Z0010 enrolled breast cancer patients onto a phase II trial studying the prognostic significance of bone marrow and sentinel node micrometastases. The current study used chi(2) analyses to determine the degree of adherence with four NQF measures among three institution types: academic, community, and teaching affiliate. RESULTS: The study revealed small but important differences in two measures. Ninety-five percent of patients from teaching affiliated institutions received whole-breast radiation compared to 92% at academic and 91% at community hospitals. Among patients who were underinsured or uninsured, a marked decrease in radiation use was noted in comparison to patients with insurance-85 versus 93%, respectively. The study also revealed a difference among institutional types in patients undergoing excisional biopsy for diagnosis. In teaching-affiliated hospitals, 28.6% underwent excisional biopsy as compared to 36.8 and 37.4% in academic and community hospitals, respectively. There was no statistically significant difference between adherence rates with the remaining two measures. Adjuvant chemotherapy was administered to patients with hormone receptor negative tumors > or =1 cm in size in 79-85% of institutions. Tamoxifen was administered to 79-82% of those patients with hormone receptor-positive cancers. CONCLUSIONS: Among breast cancer patients enrolled onto a multi-institutional clinical trial, we found a high degree of adherence with current consensus standards for adjuvant treatment, despite varied practice environments. PMID- 20309641 TI - Overexpression of activin A in oral squamous cell carcinoma: association with poor prognosis and tumor progression. AB - BACKGROUND: Both activin A, a member of transforming growth factor beta superfamily, and its inhibitor follistatin have been shown to be overexpressed in various cancers. We examined the potential role of activin A and follistatin in tissue and blood samples from patients with oral squamous cell carcinoma. METHODS: For activin A and follistatin, the expression of tissue samples from 92 patients was examined by immunohistochemical study, and the serum levels of blood samples from 111 patients and 91 healthy controls were measured by enzyme-linked immunosorbent assay. RESULTS: We found that overexpression of immunohistochemically detected activin A was correlated with positive N stage, poor histological differentiation, and perineural invasion (P = 0.029, 0.002, and 0.014, respectively). In survival analyses, patients with oral squamous cell carcinoma, whose tumors overexpressed activin A, had a worse prognosis for overall survival and disease-free survival (P = 0.009 and 0.007). However, expression of follistatin in tumor was not correlated with overall survival or disease-free survival. Serum activin A and follistatin levels in 111 untreated patients were neither significantly different from those of 91 control samples nor associated with any clinicopathological manifestations. In vitro suppression of activin A expression in OC3 cells using specific interfering RNA-attenuated cell proliferation, migration, and invasiveness. CONCLUSIONS: These findings suggest that activin A overexpression in oral squamous cell carcinomas is associated with patients' survival and may contribute to tumor progression and metastasis. PMID- 20309642 TI - Body mass index and major cancer surgery outcomes: lack of association or need for alternative measurements of obesity? AB - BACKGROUND: Although surgical studies have reported inconsistent associations between increased body mass index (BMI) and operative outcomes, the accuracy of BMI for measuring obesity has been questioned in previous epidemiologic studies. Simultaneously, BMI has known comorbidities, which may mediate the effect of BMI if included in multivariable models. We sought to examine the effect of BMI on operative outcomes after adjusting for preoperative factors. METHODS: We identified 8858 patients who underwent major thoracic, abdominal, and pelvic surgery for solid organ tumors in American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) centers from 2005 to 2007. We used multivariable analyses to assess the effect of BMI on short-term operative outcomes after controlling for covariates. RESULTS: Increased BMI was not associated with worse short-term operative outcomes in our bivariable analyses. However, patients with BMI > or = 35 had higher American Society of Anesthesiologists scores, longer operative times, and an increased number of postoperative complications (P < 0.0001). After adjusting for pre- and intraoperative factors, BMI did not predict any short-term operative outcome except for an increased total number of complications in BMI > or = 35. These results persisted after removing potential mediators from the multivariable analysis. CONCLUSIONS: In ACS NSQIP, BMI has minimal association with short-term operative outcomes after major cancer surgery. Although these findings may suggest a lack of association between obesity and cancer surgery outcomes, it confirms the previously examined limitations of BMI. Because of the rising incidence of obesity in the United States and its challenging effect on surgeon's practice, ACS NSQIP should consider exploring alternative measures of general and abdominal obesity. PMID- 20309643 TI - Complete remission of unresectable hepatocellular carcinoma treated with reduced dose of sorafenib: a case report. AB - Hepatocellular carcinoma (HCC) is a highly aggressive cancer. For patients who are diagnosed with advanced stage disease that are not surgical candidates, the disease is universally lethal. Advance has been made to extend survival with molecular target therapy, but durable complete responses are extremely rare. We report an unusual case where a 74-year-old patient with unresectable HCC received eight months of reduced-dose of sorafenib, a tyrosine kinase inhibitor, and achieved a durable complete remission. At the most recent follow up, he remains in remission 16 months after cessation of treatment, without clinical or imaging evidence of disease recurrence. PMID- 20309644 TI - Aberrant behaviours of reaction diffusion self-organisation models on growing domains in the presence of gene expression time delays. AB - Turing's pattern formation mechanism exhibits sensitivity to the details of the initial conditions suggesting that, in isolation, it cannot robustly generate pattern within noisy biological environments. Nonetheless, secondary aspects of developmental self-organisation, such as a growing domain, have been shown to ameliorate this aberrant model behaviour. Furthermore, while in-situ hybridisation reveals the presence of gene expression in developmental processes, the influence of such dynamics on Turing's model has received limited attention. Here, we novelly focus on the Gierer-Meinhardt reaction diffusion system considering delays due the time taken for gene expression, while incorporating a number of different domain growth profiles to further explore the influence and interplay of domain growth and gene expression on Turing's mechanism. We find extensive pathological model behaviour, exhibiting one or more of the following: temporal oscillations with no spatial structure, a failure of the Turing instability and an extreme sensitivity to the initial conditions, the growth profile and the duration of gene expression. This deviant behaviour is even more severe than observed in previous studies of Schnakenberg kinetics on exponentially growing domains in the presence of gene expression (Gaffney and Monk in Bull. Math. Biol. 68:99-130, 2006). Our results emphasise that gene expression dynamics induce unrealistic behaviour in Turing's model for multiple choices of kinetics and thus such aberrant modelling predictions are likely to be generic. They also highlight that domain growth can no longer ameliorate the excessive sensitivity of Turing's mechanism in the presence of gene expression time delays. The above, extensive, pathologies suggest that, in the presence of gene expression, Turing's mechanism would generally require a novel and extensive secondary mechanism to control reaction diffusion patterning. PMID- 20309645 TI - The influence of gene expression time delays on Gierer-Meinhardt pattern formation systems. AB - There are numerous examples of morphogen gradients controlling long range signalling in developmental and cellular systems. The prospect of two such interacting morphogens instigating long range self-organisation in biological systems via a Turing bifurcation has been explored, postulated, or implicated in the context of numerous developmental processes. However, modelling investigations of cellular systems typically neglect the influence of gene expression on such dynamics, even though transcription and translation are observed to be important in morphogenetic systems. In particular, the influence of gene expression on a large class of Turing bifurcation models, namely those with pure kinetics such as the Gierer-Meinhardt system, is unexplored. Our investigations demonstrate that the behaviour of the Gierer-Meinhardt model profoundly changes on the inclusion of gene expression dynamics and is sensitive to the sub-cellular details of gene expression. Features such as concentration blow up, morphogen oscillations and radical sensitivities to the duration of gene expression are observed and, at best, severely restrict the possible parameter spaces for feasible biological behaviour. These results also indicate that the behaviour of Turing pattern formation systems on the inclusion of gene expression time delays may provide a means of distinguishing between possible forms of interaction kinetics. Finally, this study also emphasises that sub-cellular and gene expression dynamics should not be simply neglected in models of long range biological pattern formation via morphogens. PMID- 20309646 TI - Impact of splenectomy on thrombocytopenia, chemotherapy, and survival in patients with unresectable pancreatic cancer. AB - BACKGROUND: Patients with unresectable pancreatic cancer (PDAC) or endocrine tumors (PET) often develop splenic vein thrombosis, hypersplenism, and thrombocytopenia which limits the administration of chemotherapy. METHODS: From 2001 to 2009, 15 patients with recurrent or unresectable PDAC or PET underwent splenectomy for hypersplenism and thrombocytopenia. The clinical variables of this group of patients were analyzed. The overall survival of patients with PDAC was compared to historical controls. RESULTS: Of the 15 total patients, 13 (87%) had PDAC and 2 (13%) had PET. All tumors were either locally advanced (n = 6, 40%) or metastatic (n = 9, 60%). The platelet counts significantly increased after splenectomy (p < 0.01). All patients were able to resume chemotherapy within a median of 11.5 days (range 6-27). The patients with PDAC had a median survival of 20 months (range 4-67) from the time of diagnosis and 10.6 months (range 0.6-39.8) from the time of splenectomy. CONCLUSIONS: Splenectomy for patients with unresectable PDAC or PET who developed hypersplenism and thrombocytopenia that limited the administration of chemotherapy, significantly increased platelet counts, and led to resumption of treatment in all patients. Patients with PDAC had better disease-specific survival as compared to historical controls. PMID- 20309647 TI - 'Slowing down when you should': initiators and influences of the transition from the routine to the effortful. AB - BACKGROUND: 'Slowing down when you should' has been described as marking the transition from 'automatic' to 'effortful' functioning in professional practice. The ability to 'slow down' is hypothesized as an important factor in expert judgment. This study explored the nature of the 'slowing down' phenomenon intraoperatively and its link to surgical judgment. METHODS: Twenty-eight surgeons across different surgical specialties were interviewed from four hospitals affiliated with a large urban university. In grounded theory tradition, data were collected and analyzed in an iterative design, using a constant comparative approach. Emergent themes were identified and a conceptual framework was developed. RESULTS: Surgeons recognized the 'slowing down' phenomenon acknowledging its link to judgment and described two main initiators. Proactively planned 'slowing down' moments were anticipated preoperatively from operation specific (tying superior thyroid vessels) or patient-specific (imaging abnormality) factors. Surgeons also described situationally responsive 'slowing down' moments to unexpected events (encountering an adherent tumor). Surgeons described several influencing factors on the slowing down phenomenon (fatigue, confidence). CONCLUSIONS: This framework for 'slowing down' assists in making tangible the previously elusive construct of surgical judgment, providing a vocabulary for considering the events surrounding these critical moments in surgery, essential for teaching, self-reflection, and patient safety. PMID- 20309648 TI - Release of metal ions from orthodontic appliances by in vitro studies: a systematic literature review. AB - In the present work, a systematic literature review on release of metal ions from orthodontic appliances under in vitro conditions is described. Detailed and schematic analysis of used materials and applied methods (immersion media, incubation time, temperature, and analytical techniques) is provided. The PubMed search identified 40 studies, among which eight met the selection criteria. One additional study was included in the review. All the authors agreed that the doses of released metal ions were far below the toxic level and the dietary intake. Although the concentrations of metal ions in immersion media greatly differed, the general conclusions were coherent. It must be underlined that the main disadvantage of in vitro tests was that the experimental setup did not reflect in vivo conditions, e.g., the presence of biofilm, which grows on the surface of the materials in oral cavity. The presence and activity of microflora to a large extent is responsible for the process of corrosion, in particular, biodeterioration. The further scheme of in vitro research should incorporate changeable conditions of oral cavity environment (pH, dynamic conditions-saliva flow) and the presence of microbiological flora (microbiological attack) in the experimental design and, first of all, the real proportions of appliance elements. PMID- 20309649 TI - Transient receptor potential melastatin 2 expression is increased following experimental traumatic brain injury in rats. AB - Traumatic brain injury (TBI) elicits a sequence of complex biochemical changes including oxidative stress, oedema, inflammation and excitotoxicity. These factors contribute to the high morbidity and mortality following TBI, although their underlying molecular mechanisms remain poorly understood. Transient receptor potential melastatin 2 (TRPM2) is a non-selective cation channel, highly expressed in the brain and immune cells. Recent studies have implicated TRPM2 channels in processes involving oxidative stress, inflammation and cell death. However, no studies have investigated the role of TRPM2 in TBI pathophysiology. In the present study, we have characterised TRPM2 mRNA and protein expression following experimental TBI. Adult male Sprague Dawley rats were injured using the impact-acceleration model of diffuse TBI with survival times between 5 and 5 days. Real-time RT-PCR (including reference gene validation studies) and semi quantitative immunohistochemistry were used to quantify TRPM2 mRNA and protein levels, respectively, following TBI. Significant increases in TRPM2 mRNA and protein expression were observed in the cerebral cortex and hippocampus of injured animals, suggesting that TRPM2 may contribute to TBI injury processes such as oxidative stress, inflammation and neuronal death. Further characterisation of how TRPM2 may contribute to TBI pathophysiology is warranted. PMID- 20309651 TI - 1H, 13C, and 15N chemical shift assignments for the RNA recognition motif of Nab3. AB - Nuclear polyadenylated RNA-binding (Nab)3 protein is an RNA-binding protein that is involved in the poly(A) independent termination pathway. Here, we report the NMR spectral assignments of RNA-recognition motif (RRM) of Nab3. The assignment will allow performing NMR structural and RNA-binding studies of Nab3 with the aim to investigate its role in the poly(A) independent termination pathway. PMID- 20309650 TI - Epiblast/germ line hypothesis of cancer development revisited: lesson from the presence of Oct-4+ cells in adult tissues. AB - The morphology of several tumors mimics developmentally early tissues; tumors often express early developmental markers characteristic for the germ line lineage. Recently, our group identified a population of very small stem cells (SCs) in murine bone marrow (BM) and other adult organs that express several markers characteristic for epiblast/germ line-derived SCs. We named these rare cells "Very Small Embryonic/Epiblast-like Stem Cells (VSELs)." We hypothesized that these cells that express both epiblast and germ line markers are deposited during early gastrulation in developing tissues and organs and play an important role in the turnover of tissue-committed (TC) SCs. To support this, we envision that the germ line is not only the origin of SCs, but also remains as a scaffold or back-up for the SC compartment in adult life. Furthermore, we noticed that VSELs are protected from uncontrolled proliferation and teratoma formation by a unique DNA methylation pattern in some developmentally crucial imprinted genes, which show hypomethylation or erasure of imprints in paternally methylated genes and hypermethylation of imprints in the maternally methylated. In pathological situations, however, we hypothesize that VSELs could be involved in the development of several malignancies. Therefore, potential involvement of VSELs in cancerogenesis could support century-old concepts of embryonic rest- or germ line origin hypotheses of cancer development. However, we are aware that this working hypothesis requires further direct experimental confirmation. PMID- 20309652 TI - Development and statistical optimization of solid lipid nanoparticles of simvastatin by using 2(3) full-factorial design. AB - The objective of this study was to develop solid lipid nanoparticles (SLNs) of simvastatin and to optimize it for independent variables (amount of glycerol monostearate, concentration of poloxamer, and volume of isopropyl alcohol) in order to achieve desired particle size with maximum percent entrapment efficiency (% EE) and percent cumulative drug release (% CDR). To achieve our goal, eight formulations (F(1)-F(8)) of SLNs were prepared by solvent injection technique and optimized by 2(3) full-factorial design. The design was validated by extra design checkpoint formulation (F(9)), and the possible interactions between independent variables were studied. The responses of the design were analyzed using Design Expert 7.1.6. (Stat-Ease, Inc, USA), and the analytical tools of software were used to draw Pareto charts and response surface plots. On the basis of software analysis, formulation F(10) with a desirability factor of 0.611 was selected as optimized formulation and was evaluated for the independent parameters. Optimized formulation showed particle size of 258.5 nm, % EE of 75.81%, with of 82.67% CDR after 55 h. The release kinetics of the optimized formulation best fitted the Higuchi model, and the recrystallization index of optimized formulation was found to be 65.51%. PMID- 20309653 TI - Cascade impactor (CI) mensuration--an assessment of the accuracy and precision of commercially available optical measurement systems. AB - Multi-stage cascade impactors (CIs) are the preferred measurement technique for characterizing the aerodynamic particle size distribution of an inhalable aerosol. Stage mensuration is the recommended pharmacopeial method for monitoring CI "fitness for purpose" within a GxP environment. The Impactor Sub-Team of the European Pharmaceutical Aerosol Group has undertaken an inter-laboratory study to assess both the precision and accuracy of a range of makes and models of instruments currently used for optical inspection of impactor stages. Measurement of two Andersen 8-stage 'non-viable' cascade impactor "reference" stages that were representative of jet sizes for this instrument type (stages 2 and 7) confirmed that all instruments evaluated were capable of reproducible jet measurement, with the overall capability being within the current pharmacopeial stage specifications for both stages. In the assessment of absolute accuracy, small, but consistent differences (ca. 0.6% of the certified value) observed between 'dots' and 'spots' of a calibrated chromium-plated reticule were observed, most likely the result of treatment of partially lit pixels along the circumference of this calibration standard. Measurements of three certified ring gauges, the smallest having a nominal diameter of 1.0 mm, were consistent with the observation where treatment of partially illuminated pixels at the periphery of the projected image can result in undersizing. However, the bias was less than 1% of the certified diameter. The optical inspection instruments evaluated are fully capable of confirming cascade impactor suitability in accordance with pharmacopeial practice. PMID- 20309654 TI - Two-step solid lipid extrusion as a process to modify dissolution behavior. AB - Extrudates based on varying ratios of the triglyceride tripalmitin and the hydrophilic polymer polyethylene glycol as matrix formers were produced as oral dosage forms with controlled release characteristics. The extrudates were processed below the melting points of the excipients and contained the hydrophobic model drug chloramphenicol. The influence of the ratio of the matrix formers on drug dissolution was investigated, with an increase in the water soluble polymer content increasing the drug release rate. In addition, the effect of varying the extrusion process on the extrudate structure and drug dissolution was investigated. Two-step extrusion was performed, which comprised an initial extrusion step of drug and one matrix component followed by milling these extrudates and a second extrusion step for the milled extrudates mixed with the second matrix component. Initial extrusion with polyethylene glycol led to increased dissolution rates, while initial extrusion with tripalmitin led to decreased dissolution rates compared to the dissolution characteristics of extrudates containing the same composition produced by one-step extrusion. Thus, two-step solid lipid extrusion can successfully be used as a process to modify the dissolution behavior of extrudates. PMID- 20309655 TI - In brief: Crowe's classification: arthroplasty in developmental dysplasia of the hip. PMID- 20309656 TI - Maggot excretions inhibit biofilm formation on biomaterials. AB - BACKGROUND: Biofilm-associated infections in trauma surgery are difficult to treat with conventional therapies. Therefore, it is important to develop new treatment modalities. Maggots in captured bags, which are permeable for larval excretions/secretions, aid in healing severe, infected wounds, suspect for biofilm formation. Therefore we presumed maggot excretions/secretions would reduce biofilm formation. QUESTIONS/PURPOSES: We studied biofilm formation of Staphylococcus aureus, Staphylococcus epidermidis, Klebsiella oxytoca, Enterococcus faecalis, and Enterobacter cloacae on polyethylene, titanium, and stainless steel. We compared the quantities of biofilm formation between the bacterial species on the various biomaterials and the quantity of biofilm formation after various incubation times. Maggot excretions/secretions were added to existing biofilms to examine their effect. METHODS: Comb-like models of the biomaterials, made to fit in a 96-well microtiter plate, were incubated with bacterial suspension. The formed biofilms were stained in crystal violet, which was eluted in ethanol. The optical density (at 595 nm) of the eluate was determined to quantify biofilm formation. Maggot excretions/secretions were pipetted in different concentrations to (nonstained) 7-day-old biofilms, incubated 24 hours, and finally measured. RESULTS: The strongest biofilms were formed by S. aureus and S. epidermidis on polyethylene and the weakest on titanium. The highest quantity of biofilm formation was reached within 7 days for both bacteria. The presence of excretions/secretions reduced biofilm formation on all biomaterials. A maximum of 92% of biofilm reduction was measured. CONCLUSIONS: Our observations suggest maggot excretions/secretions decrease biofilm formation and could provide a new treatment for biofilm formation on infected biomaterials. PMID- 20309657 TI - Revision total knee arthroplasty infection: incidence and predictors. AB - BACKGROUND: Deep infection remains one of the most devastating and costly complications after total knee arthroplasty (TKA). The risk of deep infection after revision TKA is reportedly greater than that for primary TKA; however, we do not know the exact incidence of infection after revision TKA. QUESTIONS/PURPOSES: We determined the incidence of infection after revision, the type of microorganisms involved and TKA, and the potential risk factors for this infection. METHODS: We retrospectively reviewed 475 patients (476 knees) with 499 TKA revisions performed between March 1998 and December 2005. Of the 476 knees, 91 (19%) were revised for infection and 385 (81%) were revised for aseptic failure. Preoperative history, results of physical examinations, laboratory and radiographic results, joint fluid aspiration results along with analysis of intraoperative findings were all considered to make an assessment of septic versus aseptic failure modes. Patients were followed for a minimum of 25 months (mean, 65 months; range, 25-159 months). RESULTS: Deep infection developed in 44 of the 476 knees (9%). The infection rate was higher in patients undergoing revision for infection than in patients with aseptic revisions: 21% (23 of 91) and 5% (21 of 385), respectively. Revision for infection, higher Charlson index, and diagnosis other than osteoarthritis at the time of primary TKA predicted infection of the revision. The risk of infection for patients undergoing TKA revisions was 10-fold higher than for patients undergoing primary TKA at our institution. CONCLUSIONS: Infection of primary TKA is the most important risk factor for subsequent infection of TKA revisions. LEVEL OF EVIDENCE: Level III, prognostic study. See Guidelines for Authors for a complete description of levels of evidence. PMID- 20309658 TI - Outcomes of revision total knee arthroplasty after methicillin-resistant Staphylococcus aureus infection. AB - BACKGROUND: The incidence of infection by methicillin-resistant Staphylococcus aureus (MRSA) in total knee arthroplasty (TKA) is becoming a more frequent concern, as increased morbidity following TKA has been reported for infections by resistant organisms. This study investigates whether MRSA infections are associated with decreased functional scores. QUESTIONS/PURPOSES: We therefore compared the functional scores, operative times, and rates of reinfection of revision TKA following MRSA infection versus other indications for revision. METHODS: We retrospectively reviewed charts of 101 patients (103 knees) who underwent mobile bearing TKA revision from January 2003 to September 2006, with a minimum clinical followup of 2 years in 45 knees (44%). We obtained the following indices: WOMAC, Activities of Daily Living Score (ADLS), SF-36, and Knee Society scores (KSS). Three groups of revisions were compared: MRSA infection (n = 6), non-MRSA infection (n = 9), and aseptic failure (n = 30). The three groups were similar in demographics and comorbidities. RESULTS: The MRSA (166 minutes) and non-MRSA groups (149 minutes) had longer operative times than the aseptic group (121 minutes). With numbers available, there were no differences in ROM, WOMAC, ADLS, KSS, and SF-36, with MRSA separate or combined with all infections. Infection recurrence between MRSA-infected knees and non-MRSA-infected knees was similar. CONCLUSIONS: While our study was underpowered to detect functional differences between MRSA-infected knees and non-MRSA-infected knees it does add data to the literature. Knees revised for infection have longer operative times and more frequent infection after revision. The reason for increased operative times is unclear. LEVEL OF EVIDENCE: Level III, therapeutic study. See the Guidelines for Authors for a complete description of levels of evidence. PMID- 20309659 TI - High long-term survival of bulk femoral head autograft for acetabular reconstruction in cementless THA for developmental hip dysplasia. AB - BACKGROUND: Deficient acetabula associated with acetabular dysplasia cause difficulty achieving adequate coverage of the acetabular component during THA. Autografting with the removed femoral head has been used for several decades to achieve better coverage, but the long-term benefits of this technique remain controversial, with some series reporting high rates of graft resorption and collapse. QUESTIONS/PURPOSES: We evaluated the fate of bulk femoral head autograft for acetabular reconstruction in cementless THA for developmental hip dysplasia. PATIENTS AND METHODS: We retrospectively reviewed 70 patients (83 hips) (68 women, two men) with a mean age of 57 years at index surgery. According to the classification of Crowe et al. for hip dysplasia, 10 hips were classified as Type I, 45 as Type II, 19 as Type III, and nine as Type IV. Minimum followup was 9 years (mean, 11 years; range, 9-14 years). RESULTS: We observed no collapsed grafts. In all patients we observed disappearance of the host-graft interface and appearance of radiodense bands in the grafts bridging host iliac bone and at the lateral edges of the acetabular sockets; remodeling with definite trabecular reorientation was seen in 90%. The 10-year survival rate without acetabular revision for any reason was 94%. The mean Merle d'Aubigne and Postel hip score improved from a mean of 9.1 preoperatively to 17.2 at last followup. CONCLUSIONS: Cementless THA combined with autologous femoral bone graft in patients with developmental dysplasia resulted in a high rate of survival. Structural bone grafting achieved a stable construct until osseointegration occurred. We believe the radiodense bands represent a radiographic sign of successful completion of repair of the deficient acetabulum. Congruous and stable contact of the cancellous portion of the graft to the host bed by impaction and use of improved porous cementless sockets may be associated with successful socket survival. LEVEL OF EVIDENCE: Level IV, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence. PMID- 20309660 TI - N-acetylcysteine protects striated muscle in a model of compartment syndrome. AB - BACKGROUND: To avoid ischemic necrosis, compartment syndrome is a surgical emergency treated with decompression once identified. A potentially lethal, oxidant-driven reperfusion injury occurs after decompression. N-acetylcysteine is an antioxidant with the potential to attenuate the reperfusion injury. QUESTIONS/PURPOSES: We asked whether N-acetylcysteine could preserve striated muscle contractility and modify neutrophil infiltration and activation after simulated compartment syndrome release. MATERIALS AND METHODS: Fifty-seven rats were randomized to control, simulated compartment syndrome, and simulated compartment syndrome plus N-acetylcysteine groups. We isolated the rodent cremaster muscle on its neurovascular pedicle and placed it in a pressure chamber. Chamber pressure was elevated above critical closing pressure for 3 hours to simulate compartment syndrome. Experiments were concluded at three times: 1 hour, 24 hours, and 7 days after decompression of compartment syndrome. We assessed twitch and tetanic contractile function and tissue myeloperoxidase activity. Ten additional rats were randomized to control and N-acetylcysteine administration after which neutrophil respiratory burst activity was assessed. RESULTS: The simulated compartment syndrome decreased muscle contractility and increased muscle tissue myeloperoxidase activity compared with controls. Treatment with N-acetylcysteine preserved twitch and tetanic contractility. N acetylcysteine did not alter neutrophil infiltration (myeloperoxidase activity) acutely but did reduce infiltration at 24 hours, even when given after decompression. N-acetylcysteine reduced neutrophil respiratory burst activity. CONCLUSION: N-acetylcysteine administration before or after simulated compartment syndrome preserved striated muscle contractility, apparently by attenuating neutrophil activation and the resultant oxidant injury. CLINICAL RELEVANCE: Our data suggest a potential role for N-acetylcysteine in the attenuation of muscle injury after release of compartment syndrome and possibly in the prophylaxis of compartment syndrome. PMID- 20309661 TI - Seroprevalence of human herpes simplex, hepatitis B and epstein-barr viruses in children with acute lymphoblastic leukemia in southern iran. AB - To investigate the seroprevalence of Herpes Simplex Viruses (HSV1 and HSV2), Ebstein-Barr Virus (EBV) and Hepatitis B Virus (HBV) in children with acute lymphoblastic leukemia (ALL) in southern Iran. 90 patients with ALL and 90 age sex matched healthy participants were enrolled in this study. Antibodies (IgG) against HBsAg, HSV1, HSV2, EBV different antigens including Epstein-Barr nuclear antigen-1 (EBNA-1), viral capsid antigen (VCA) and early antigen (EA) were measured by enzyme-linked immunosorbent assay (ELISA). There were 54 (60%) male and 36 (40%) female in both study groups with mean age of 8.47 +/- 3.61 and 8.61 +/- 2.84 years in case and control group respectively (P = 0.812). The prevalence of antibodies against HBsAg (P = 0.002), HSV1 (P < 0.0001), VCA (P = 0.021) and EA (P < 0.0001) antigens of EBV were significantly higher in ALL patients. With the results of this study, we could not exclude a connection between these viral infections and later leukemogenesis in childhood ALL, although nor latent infection nor congenital infection cannot be excluded by this method. PMID- 20309662 TI - R72P polymorphism of TP53 in ulcerative colitis patients is associated with the incidence of colectomy, use of steroids and the presence of a positive family history. AB - P53 tumor suppressor protein is one of the pivotal regulators for genome integrity, cell cycle and apoptosis. The most commonly and extensively studied single nucleotide polymorphism (SNP) of p53 is Arg>Pro substitution on codon 72 (R72P). Although we know that the SNP has unique functional effects on the protein, its clinical significance is not clearly identified yet. Aim of the study was to access the relationship between R72P genotype distribution and clinical variables in patients with ulcerative colitis (UC) and colorectal cancer (CRC). Genomic DNA samples were extracted from 95 UC, 50 CRC, and 219 healthy controls. R72P genotype analysis was carried out with polymerase chain reaction following by restriction enzyme digestion. We observed that Pro allele carriage is a strong risk factor for CRC (OR = 3.03; 95%CI = 1.91-2.40; p = 0.003), but only modest association with UC (OR = 1.61; 95%CI = 0.98-2.65; p = 0.059) (Pro/Pro and Pro/Arg genotypes vs. Arg/Arg genotype). We did not find any correlation between genotype distribution of the polymorphism and clinical parameters of CRC, but in UC, Pro/Pro genotype was significantly related to an inflammatory bowel disease family history (OR = 8.0; 95%CI = 1.68-38.08, p = 0.015), and Arg/Pro genotype was significantly associated with the history of disease-related colectomy (OR = 17.77; 95%CI = 0.98-323.34, p = 0.012) and steroid use (OR = 10.14; 95%CI = 2.63-39.12, p = 0.0002). Our data suggest that R72P variant seems to be associated with high risk for development of CRC but carries low risk for development of UC. R72P genotypes might be a useful predictive marker for surgical and medical treatment of UC. PMID- 20309663 TI - Redox mechanism of neurotoxicity by a serotonin-acrolein polymeric melanoid. AB - Postoperative cognitive dysfunction may be associated with the toxic products of lipid peroxidation, such as the alpha,beta-unsaturated aldehyde acrolein, which accumulates in aging. We previously identified an acrolein-mediated, serotonin derived melanoid product, or SDM. This study further characterizes this putative novel neuromelanin, which is not made from catecholamines. In addition to its strong protein-binding properties, we observed that SDM binds Fe(2+) readily and exhibits complex redox characteristics. SDM may exist as a two-dimensional network of polymers that coalesce into larger entities exhibiting electroactive properties. These observations suggest that SDM may contribute to the decline in cognition due to focal degeneration from SDM-mediated free-radical production. We know that inhalational anesthetics sequester acrolein, which is toxic to neurons, and we propose that the local increase in acrolein depletes serotonin levels and enhances neuronal vulnerability through the production of neuromelanin-like structures, such as SDM. PMID- 20309664 TI - Amyloid-beta precursor protein induces glial differentiation of neural progenitor cells by activation of the IL-6/gp130 signaling pathway. AB - Although amyloid precursor protein (APP) due to the cytotoxicity of Abeta peptides, has been intensively studied, the physiological role of APP still remains wrapped up in veil. In this article, we propose that alpha-cleaved ectodomain of APP (sAPPalpha) stimulates the IL-6/gp130 signaling pathway for induction of gliogenesis within neural progenitor cells (NPCs). In our previous study, a high dose of APP differentiated NPCs into glial fibrillary acidic protein (GFAP) positive cells. In order to elucidate the mechanism of APP-induced glial differentiation, we examined the effects of sAPPalpha on the IL-6/gp130 signaling pathway. Application of sAPPalpha promoted mRNA expression of gp130, ciliary neurotrophic factor (CNTF), and Janus kinase 1 (JAK1). sAPPalpha stimulated the glial differentiation by upregulating the expression and phosphorylation of gp130. While mRNA expression of STAT3 was unchanged, phosphorylation of STAT3-Tyr705 gradually increased. Application of small interference RNA (siRNA) for STAT3 suppressed GFAP expression even in the presence of APP. Treatment with siRNA or inhibitor, AG490, of JAK1 efficiently suppressed STAT3 phosphorylation and GFAP expression. Upregulation of CNTF was observed in either short- or long-term treatment with sAPPalpha. RNA's interference of CNTF dose-dependently inhibited GFAP expression upregulated by treatment with sAPPalpha. This study suggests that the IL-6/gp130 signaling pathway is involved in sAPPalpha-induced glial differentiation of NPCs. Although further investigation is needed, this study may provide insight into the mechanism of glial differentiation of NPCs under pathological conditions in Alzheimer's disease or Down syndrome. PMID- 20309665 TI - Epigenetically regulated imprinted genes and foetal programming. AB - Genomic imprinting is a widespread epigenetic phenomenon in mammals and many imprinted genes are expressed in the developing hypothalamus and placenta. The placenta and brain are very different structures with very different roles, but in the pregnant mother they functionally interact coordinating and ensuring the provision of nutrients, timing of parturition and priming of hypothalamus for maternal care and nurturing. This interaction has been evolutionarily fine-tuned to optimise infant survival such that when resources are poor, the mother 'informs' this condition to the foetus producing a thrifty phenotype that is adapted to survive scarce resources after birth. PMID- 20309667 TI - Contralateral breast dose from chest wall and breast irradiation: local experience. AB - Second cancer induction in the contralateral breast (CB) is an issue of some concern in breast radiotherapy especially for women under the age of 45 years at the time of treatment. The CB dose from 2-field and 3-field techniques in post mastectomy chest wall irradiations in an anthropomorphic phantom as well as in patients were measured using thermoluminescent dosimeters (TLDs) at the local radiotherapy center. Breast and chest wall radiotherapy treatments were planned conformally (3D-CRT) and delivered using 6-MV photons. The measured CB dose at the surface fell sharply with distance from the field edge. However, the average ratio of the measured to the calculated CB dose using the pencil beam algorithm at the surface was approximately 53%. The mean and median measured internal dose at the posterior border of CB in a phantom was 5.47+/-0.22 cGy and 5.44 cGy, respectively. The internal CB dose was relatively independent of depth. In the present study the internal CB dose is 2.1-4.1% of the prescribed dose which is comparable to the values reported by other authors. PMID- 20309668 TI - Anatomical basis of the suprascapular nerve entrapment, and clinical relevance of the supraspinatus fascia. AB - INTRODUCTION: The entrapment of the suprascapular nerve (SSN) is commonly considered at the level of the suprascapular notch and more rarely in the spinoglenoid notch. Recent per-operative findings showed a compression of the SSN along its course in the supraspinatus fossa. The removal of a fascia for releasing the nerve between the suprascapular notch and spinoglenoid notch led us to purchase an anatomical study. MATERIALS AND METHODS: 30 cadaver shoulders have been dissected. The morphological features about the suprascapular notch, the supraspinatus fascia, and the spinoglenoid notch have been observed. Histological studies of the fascia and the spinoglenoid ligament have been performed. Morphometric parameters such as shape of the suprascapular notch, diameters of the SSN before and after the suprascapular notch, distance between the two notches, length of the course of the SSN into the supraspinatus fossa, diameters of the spinoglenoid notch have been measured. RESULTS: The shape of the suprascapular notch could be seen as "U"- or "V" as previously reported. The fascia was quite constant (completely identified in 29 shoulders) and was the lateral extension of the supraspinatus fascia. The SSN coursed between the bone and the fascia and was surrounded by fat tissue. This fascia was thickened at the level of the spinoglenoid notch and joined the infraspinatus fascia. The spinoglenoid ligament was seen in 28 shoulders. DISCUSSION AND CONCLUSION: In pathologic and post-trauma conditions, the fascia can be retracted or thickened and the SSN may be entrapped along its course in the supraspinatus fossa, between the suprascapular notch and the spinoglenoid notch and without any compression in any notch. These anatomical data lead us to consider that a tunnel syndrome may concern the SSN. PMID- 20309669 TI - [Skin and eyes]. AB - Numerous diseases affect both skin and eyes due to similar ontogenetic origin. The eye is the second most common site of melanoma after the skin. The eyelids are predisposed for development of toxic and allergic dermatitis as the skin in this region is four times thinner than the other facial skin. The differential diagnosis must include atopic and seborrhoeic eyelid dermatitis. Atopic and vernal keratoconjunctivitis are associated with atopic eczema. Various immunobullous disorders involve the conjunctiva with varying severity. Side effects of dermatologic treatments with glucocorticoids, antimalarials, psoralens, retinoids, or tetracyclines may involve the eye. PMID- 20309671 TI - [Analysis of intracardial electrograms in pacemakers and ICD systems by Biotronik]. AB - Detailed analysis of stored electrograms is essential for the interpretation of arrhythmias, programming changes, and optimization of the medical therapy in patients with implanted pacemakers and defibrillators. The physician who cares for patients with implantable electrical devices has to be able to understand the detection and treatment algorithms of those devices. Biotronik pacemakers of newer generations are capable of storing intracardiac electrograms. Earlier devices store up to 12 electrograms of 10 s duration after certain trigger events, like atrial tachycardia or high ventricular rates. Cardiac resynchronization systems can store electrograms after patient activation with magnets in addition to the above mentioned trigger-activated electrograms. Defibrillators store intracardiac electrograms during tachycardia episodes with near-field and far-field electrograms of the right ventricular lead in addition to the markers in single and dual chamber defibrillators (in addition to an atrial electrogram) and near field electrograms of the atrial, the right, and the left ventricular electrode in addition to the markers in resynchronization systems. Each channel has a maximum storing capacity of 32 min. If there are more episodes than storing capacity, electrograms of older episodes will be overwritten, but if the newer episodes are all classified as supraventricular, the last two ventricular episodes (VT or VF) will remain in the episode memory. This article describes stored electrograms, detection, and treatment algorithms of implantable cardiac devices manufactured by Biotronik. PMID- 20309672 TI - [Stored electrograms in pacemakers and ICDs from St. Jude Medical]. AB - Stored electrograms (EGMs) significantly improve pacemaker and ICD therapy. In pacemaker systems, the main focus of stored EGMs concerns the manual control of device detection of atrial tachyarrhythmias, especially atrial fibrillation. In ICD therapy, stored EGMs allow the discrimination of adequate and inadequate detection of ventricular tachycardia. This review presents the implementation of stored EGMs in systems from St. Jude Medical and explains the mode of EGM storage and marker annotations, which are useful for interpretation of stored EGMs and to understand the way the device interprets the EGM. Clinical examples illustrate appropriate and inappropriate device classifications. PMID- 20309673 TI - [Pacemaker ECG quiz no. 21: Strange ECG after DDDR pacemaker implantation]. AB - In a patient with sinus node disease (intermittent sinus arrest with symptomatic pauses >4 s), a DDDR pacemaker with a dedicated algorithm to avoid unnecessary ventricular pacing (mode switch between AAIR and DDDR) was implanted. The pacemaker ECG after implantation shows an unexpected tachycardia. PMID- 20309674 TI - Basic science and clinical application of stem cells in veterinary medicine. AB - Stem cells play an important role in veterinary medicine in different ways. Currently several stem cell therapies for animal patients are being developed and some, like the treatment of equine tendinopathies with mesenchymal stem cells (MSCs), have already successfully entered the market. Moreover, animal models are widely used to study the properties and potential of stem cells for possible future applications in human medicine. Therefore, in the young and emerging field of stem cell research, human and veterinary medicine are intrinsically tied to one another. Many of the pioneering innovations in the field of stem cell research are achieved by cooperating teams of human and veterinary medical scientists.Embryonic stem (ES) cell research, for instance, is mainly performed in animals. Key feature of ES cells is their potential to contribute to any tissue type of the body (Reed and Johnson, J Cell Physiol 215:329-336, 2008). ES cells are capable of self-renewal and thus have the inherent potential for exceptionally prolonged culture (up to 1-2 years). So far, ES cells have been recovered and maintained from non-human primate, mouse (Fortier, Vet Surg 34:415 423, 2005) and horse blastocysts (Guest and Allen, Stem Cells Dev 16:789-796, 2007). In addition, bovine ES cells have been grown in primary culture and there are several reports of ES cells derived from mink, rat, rabbit, chicken and pigs (Fortier, Vet Surg 34:415-423, 2005). However, clinical applications of ES cells are not possible yet, due to their in vivo teratogenic degeneration. The potential to form a teratoma consisting of tissues from all three germ lines even serves as a definitive in vivo test for ES cells.Stem cells obtained from any postnatal organism are defined as adult stem cells. Adult haematopoietic and MSCs, which can easily be recovered from extra embryonic or adult tissues, possess a more limited plasticity than their embryonic counterparts (Reed and Johnson, J Cell Physiol 215:329-336, 2008). It is believed that these stem cells serve as cell source to maintain tissue and organ mass during normal cell turnover in adult individuals. Therefore, the focus of attention in veterinary science is currently drawn to adult stem cells and their potential in regenerative medicine. Also experience gained from the treatment of animal patients provides valuable information for human medicine and serves as precursor to future stem cell use in human medicine.Compared to human medicine, haematopoietic stem cells only play a minor role in veterinary medicine because medical conditions requiring myeloablative chemotherapy followed by haematopoietic stem cell induced recovery of the immune system are relatively rare and usually not being treated for monetary as well as animal welfare reasons.In contrast, regenerative medicine utilising MSCs for the treatment of acute injuries as well as chronic disorders is gradually turning into clinical routine. Therefore, MSCs from either extra embryonic or adult tissues are in the focus of attention in veterinary medicine and research. Hence the purpose of this chapter is to offer an overview on basic science and clinical application of MSCs in veterinary medicine. PMID- 20309675 TI - Modeling languages for biochemical network simulation: reaction vs equation based approaches. AB - Biochemical network modeling and simulation is an essential task in any systems biology project. The systems biology markup language (SBML) was established as a standardized model exchange language for mechanistic models. A specific strength of SBML is that numerous tools for formulating, processing, simulation and analysis of models are freely available. Interestingly, in the field of multidisciplinary simulation, the problem of model exchange between different simulation tools occurred much earlier. Several general modeling languages like Modelica have been developed in the 1990s. Modelica enables an equation based modular specification of arbitrary hierarchical differential algebraic equation models. Moreover, libraries for special application domains can be rapidly developed. This contribution compares the reaction based approach of SBML with the equation based approach of Modelica and explains the specific strengths of both tools. Several biological examples illustrating essential SBML and Modelica concepts are given. The chosen criteria for tool comparison are flexibility for constraint specification, different modeling flavors, hierarchical, modular and multidisciplinary modeling. Additionally, support for spatially distributed systems, event handling and network analysis features is discussed. As a major result it is shown that the choice of the modeling tool has a strong impact on the expressivity of the specified models but also strongly depends on the requirements of the application context. PMID- 20309676 TI - Mental disorder in Polish families: is diagnosis a predictor of caregiver's burden? AB - OBJECTIVE: To test whether a caregiver's burden is associated with the patient's psychiatric diagnosis and to find other predictors of family burden; to provide Polish data on the issue to international literature. METHOD: Of 377 eligible subjects, 141 were interviewed on admission to the mental hospital using Brief Psychiatric Rating Scale, Manchester Short Assessment of Quality of Life, Groningen Social Disability Schedule and Client's Sociodemographic and Clinical History Inventory. Their caregivers completed the Involvement Evaluation Questionnaire (IEQ). Subjects were grouped according to ICD-10 diagnoses: schizophrenia (n = 55), depression (n = 61), and anxiety and personality disorders (n = 25). Highly aggressive, suicidal and somatically unstable patients were excluded along with patients below 18 and over 65 years. Statistics included multiple regression analysis, ANOVA, Kruskal-Wallis and chi-square tests. RESULTS: Diagnostic groups differed with respect to sociodemographics, psychopathology and quality of life, but not with respect to mean level of social functioning. Despite between-group differences, the caregiver's burden did not differ according to the diagnostic group. Of the four dimensions of burden, "worrying" and "urging" scored the highest. Majority of caregivers worried about their relative's general health (82%), future (74%) and financial status (66%). Caregivers' characteristics and not patients' explained the largest proportion of the family burden variance (almost 23% for IEQ Tension). Higher burden seemed to be associated with the carer's age, being a parent and number of hours spent weekly on caring for the ill relative. Lower burden was associated with the carers' subjective feelings of being able to cope with problems and to pursue their own activities. Longer history of patient's illness led to higher IEQ Tension. Polish caregivers were affected by their role in the same way as their counterparts abroad, but more of them were worried. CONCLUSIONS: The caregiver's burden seems to be independent of the patient's diagnosis, but other factors contribute to the perceived burden, many of which are on the caregiver's part. In Poland, the overall family burden may be attributed mostly to worrying about a mentally ill relative and his future. All caregivers may benefit from psychoeducation and family interventions usually planned for those caring for relatives with schizophrenia. PMID- 20309677 TI - Years from menopause-to-surgery is a major factor in the post-operative subjective outcome for pelvic organ prolapse. AB - INTRODUCTION AND HYPOTHESIS: The purpose of the current study was to determine the main factors associated with post-operative subjective outcome in post menopausal patients with pelvic organ prolapse. METHODS: Ninety-four women were selected among patients who underwent surgery for grade 3 or 4 prolapse. The outcome was evaluated by the Patient Global Impression of Improvement (PGI-I) scale. Multivariate ordinal regression analysis was performed. RESULTS: The number of patients with improvement (1 or 2 on the PGI-I scale) was 88 (93.7%). Age and years from menopause-to-surgery were negatively (beta = -0.16, P = 0.01) and positively (beta = 0.14, P = 0.01) associated with the PGI-I scale. The aging effect was lost after adjusting for prolapse grade. CONCLUSION: The greater the number of years from menopause-to-pelvic organ prolapse surgery, the less satisfied were the patients. The association between older patients and greater satisfaction appears to be a confounding effect of prolapse grade. PMID- 20309678 TI - Risk of atrial fibrillation associated with use of bisphosphonates and other drugs against osteoporosis: a cohort study. AB - We studied the association between bisphosphonate use and risk of atrial fibrillation or flutter and the effect of confounders such as heart and lung disease in a nationwide retrospective cohort from Denmark. All users of bisphosphonates and other drugs against osteoporosis between 1996 and 2006 (n = 103,562) were the exposed group and three age- and gender-matched controls from the general population (n = 310,683) were the nonexposed group. The main outcome measure was atrial fibrillation or atrial flutter. Before initiation of treatment against osteoporosis, no excess of atrial fibrillation or flutter was present for any drug except for etidronate (OR = 1.22, 95% CI 1.15-1.29). After initiation of treatment, raloxifene was not associated with any excess risk of atrial fibrillation (OR = 0.98, 95% CI 0.72-1.33). Etidronate (HR = 1.08, 95% CI 1.02 1.14) and alendronate (HR = 1.09, 95% CI 1.00-1.20) were associated with an excess risk of atrial fibrillation after treatment start if statistical adjustments were made for cardiovascular disease. However, this association disappeared upon statistical adjustment for chronic obstructive pulmonary disease (COPD) (etidronate HR = 1.04, 95% CI 0.98-1.10; alendronate HR = 1.05, 95% CI 0.96-1.15). In patients using etidronate (12.5% vs. 3.8%) and alendronate (11.4% vs. 4.6%) major differences were present in prevalence of COPD at start of treatment compared to matched controls. In conclusion, oral bisphosphonates do not seem to be associated with an excess risk of atrial fibrillation. Any excess risk seen in prior studies may be due to confounding from COPD. PMID- 20309679 TI - The structure of dopamine induced alpha-synuclein oligomers. AB - Inclusions of aggregated alpha-synuclein (alpha-syn) in dopaminergic neurons are a characteristic histological marker of Parkinson's disease (PD). In vitro, alpha syn in the presence of dopamine (DA) at physiological pH forms SDS-resistant non amyloidogenic oligomers. We used a combination of biophysical techniques, including sedimentation velocity analysis, small angle X-ray scattering (SAXS) and circular dichroism spectroscopy to study the characteristics of alpha-syn oligomers formed in the presence of DA. Our SAXS data show that the trimers formed by the action of DA on alpha-syn consist of overlapping worm-like monomers, with no end-to-end associations. This lack of structure contrasts with the well-established, extensive beta-sheet structure of the amyloid fibril form of the protein and its pre-fibrillar oligomers. We propose on the basis of these and earlier data that oxidation of the four methionine residues at the C- and N terminal ends of alpha-syn molecules prevents their end-to-end association and stabilises oligomers formed by cross linking with DA-quinone/DA-melanin, which are formed as a result of the redox process, thus inhibiting formation of the beta-sheet structure found in other pre-fibrillar forms of alpha-syn. PMID- 20309680 TI - Detection of low-grade prosthetic joint infections using 99mTc-antigranulocyte SPECT/CT: initial clinical results. AB - PURPOSE: Low-grade joint infections are characterized by infiltration of granulocytes, which mediate aspects of inflammatory changes. We evaluated retrospectively the contribution of SPECT/CT as an addition to planar scintigraphy with (99m)Tc-labelled antigranulocyte antibodies for diagnosing and localizing low-grade joint infections. METHODS: Planar scintigraphy using (99m)Tc labelled antigranulocyte BW 250/183 antibodies was performed in 31 patients with suspected joint infections at 5 min, 5 h and 24 h after injection, with additional SPECT/CT performed 6 h after injection. With reference to gold standard clinical data, we assessed the diagnostic sensitivity of scintigraphy alone and in conjunction with SPECT/CT. RESULTS: Joint infections were diagnosed clinically in 9 of the 31 patients (1 hip and 8 knee prostheses). Planar scintigraphy revealed 6 true-positives, 13 true-negatives, 9 false-positives and 3 false-negative results, indicating sensitivity, specificity, positive and negative predictive values of, respectively, 0.66, 0.60, 0.4 and 0.81. With the addition of SPECT images, corresponding sensitivity, specificity, positive and negative predictive values increased to 0.89, 0.45, 0.40 and 0.91. Implementation of fused SPECT/CT led to a further increase to 0.89, 0.73, 0.57 and 0.94. CONCLUSION: Relative to planar scintigraphy, SPECT with and without CT substantially improved the utility of imaging with (99m)Tc-labelled antigranulocyte antibodies for diagnosis and localization of suspected joint infections. Optimal accuracy was obtained through image fusion, which permitted anatomical allocation of foci of pathological tracer accumulation as well as providing information on the extent of the infection. This imaging method seems suited for selection of patients requiring surgical therapy. PMID- 20309681 TI - Skin metastasis of follicular thyroid carcinoma. PMID- 20309682 TI - The SPECT tracer [123I]ADAM binds selectively to serotonin transporters: a double blind, placebo-controlled study in healthy young men. AB - PURPOSE: The tracer (123)I-2-([2-({dimethylamino}methyl)phenyl]thio)-5 iodophenylamine ([(123)I]ADAM) has been developed to image serotonin transporters (SERTs) with SPECT. Preclinical studies have shown that [(123)I]ADAM binds selectively to SERTs. Moreover, initial human studies have shown that [(123)I]ADAM binding could be blocked by selective serotonin reuptake inhibitors (SSRIs). However, in humans it has not been proven that [(123)I]ADAM binds selectively to SERTs. METHODS: We examined the in vivo availability of SERTs in 12 healthy young volunteers 5 h after bolus injection of [(123)I]ADAM. To evaluate the selectivity of binding, four participants were pretreated (double blinded design) with placebo, four with paroxetine (20 mg) and four with the dopamine/norepinephrine blocker methylphenidate (20 mg). SPECT studies were performed on a brain-dedicated system (Neurofocus), and the SPECT images were coregistered with individual MR scans of the brain. ADAM binding in SERT-rich brain areas and cerebellar cortex (representing non-specific binding) was assessed by drawing regions of interest (ROIs) on the individual MR images. Specific to non-specific ratios were used as the outcome measure. RESULTS: We found that specific to non-specific ratios were statistically significantly lower in paroxetine-pretreated participants than in placebo- or methylphenidate pretreated participants. No such difference was found between groups pretreated with placebo or methylphenidate. CONCLUSION: Our preliminary findings suggest that [(123)I]ADAM binds selectively to SERTs in human brain. PMID- 20309683 TI - Clinical value of FDG PET/CT in the diagnosis of suspected recurrent ovarian cancer: is there an impact of FDG PET/CT on patient management? AB - PURPOSE: The aim of this study was to evaluate the clinical value of FDG PET/CT in patients with suspected ovarian cancer recurrence as compared with diagnostic CT, and to assess the impact of the results of FDG PET/CT on treatment planning. METHODS: Included in this retrospective study were 60 patients with suspected recurrent ovarian cancer who had previously undergone primary debulking surgery and had been treated with adjuvant chemotherapy. Diagnostic CT and FDG PET/CT imaging were performed for all patients as clinically indicated. The changes in the clinical management of patients according to the results of FDG PET/CT were also analysed. RESULTS: FDG PET/CT was performed in 21 patients with a previously negative or indeterminate diagnostic CT scan, but an elevated CA-125 level, and provided a sensitivity of 95% in the detection of recurrent disease. FDG PET/CT revealed recurrent disease in 19 patients. In 17 of 60 patients, the indication for FDG PET/CT was an elevated CA-125 level and an abnormal diagnostic CT scan to localize accurately the extent of disease. FDG PET/CT scans correctly identified recurrent disease in 16 of the 17 patients, a sensitivity of 94.1%. Moreover, FDG PET/CT was performed in 18 patients with clinical symptoms of ovarian cancer recurrence, an abnormal diagnostic CT scan, but a normal CA-125 level. In this setting, FDG PET/CT correctly confirmed recurrent disease in seven patients providing a sensitivity of 100% in determining recurrence. In four patients, FDG PET/CT was carried out for the assessment of treatment response. Three of four scans were classified as true-negative indicating a complete response. In the other patient, FDG PET/CT identified progression of disease. In total, 45 (75%) of the 60 patients had recurrent disease, in 14 (31.1%) documented by histopathology and in 31 (68.9%) on clinical follow-up, while 15 (25%) had no evidence of recurrent disease. The overall sensitivity, specificity, accuracy, and positive and negative predictive value of FDG PET/CT were significantly superior to those of diagnostic CT (95.5% vs. 55.5%, 93.3% vs. 66.6%, 95% vs. 58.3%, 97.7% vs. 83.3%, 87.7% vs. 33.3%, respectively; p = 0.02) in the detection of recurrent ovarian cancer. FDG PET/CT changed the management in 31 patients (51.6%). It led to the use of previously unplanned treatment procedures in 19 patients (61.2%) and the avoidance of previously planned therapeutic procedures in 12 patients (38.8%). CONCLUSION: Our results confirm that FDG PET/CT is a superior posttherapy surveillance modality for the detection of recurrent ovarian cancer than diagnostic CT imaging. Furthermore, integrated FDG PET/CT was useful specifically in optimizing the treatment plan and it might play an important role in treatment stratification in the future. PMID- 20309685 TI - Can an undetectable value of TG and a negative neck ultrasound study be considered reliable methods to assess the completeness of thyroid ablation? PMID- 20309686 TI - Imaging of proliferation with 18F-FLT PET/CT versus 18F-FDG PET/CT in non-small cell lung cancer. AB - PURPOSE: To compare the diagnostic efficacies of (18)F-FLT and (18)F-FDG PET/CT in non-small-cell lung cancer (NSCLC), focusing on the correlation between FLT and FDG tumour uptake and tumour cell proliferation as indicated by the cyclin D1 labelling index. METHODS: A total of 31 patients with NSCLC underwent FLT and FDG PET/CT scanning followed by surgery. PET/CT images were compared with the pathology. Tumour cell proliferation was assessed by cyclin D1 immunohistochemistry. RESULTS: The sensitivities of FLT and FDG PET/CT for the primary lesion were 74% and 94%, respectively (p=0.031). For N staging, 77% patients were correctly staged, 6% overstaged, 16% understaged by FLT, while the values for FDG were 77%, 16% and 6%, respectively. The sensitivity, specificity, accuracy, and positive predictive value with FLT for lymph nodes were 65%, 98%, 93% and 89%, respectively, and 85%, 84%, 84% and 52% with FDG (p<0.01).Tumour SUV of FLT was significantly correlated with the cyclin D1 labelling index (r=0.644; p<0.01), but the SUV of FDG was not significantly correlated (r=0.293; p>0.05). CONCLUSION: In terms of N staging, FLT PET/CT resulted in understaging of more patients but overstaging of fewer patients, and for regional lymph nodes showed better specificity, accuracy and positive predictive value than FDG PET/CT in NSCLC. Tumour FLT uptake was correlated with tumour cell proliferation as indicated by the cyclin D1 labelling index, suggesting that further studies are needed to evaluate the use of FLT PET/CT for the assessment of therapy response to anticancer drugs. PMID- 20309687 TI - Pancytopenia secondary to hypopituitarism may just be due to hypothyroidism alone. PMID- 20309688 TI - Evaluating bleeding severity in immune thrombocytopenia (ITP). AB - Despite immune thrombocytopenia (ITP) being one of the most common conditions encountered by the pediatric hematologist, relatively few prospective investigations of ITP exist, and treatment approaches remain highly variable. The ideal prospective clinical trial would use a reduction in severe bleeding as an outcome; however, recent data shows that due to the rarity of severe bleeding events such a trial is not feasible due to the large number of children needed to be enrolled on such studies. Therefore, platelet count is often used a surrogate risk for bleeding severity and an increase in platelet count as the primary outcome in clinical trials. Reliance solely on the platelet count fails to account for relevant patient-related outcomes, among them bleeding severity. Bleeding assessment instruments published to date lack validity and reliability. Therefore, rigorous methods to design and analysis of patient-related outcome measurement tools need to be applied. Once designed appropriately, these measures can be applied to enhance research and help to guide treatment for those patients who truly need it. PMID- 20309689 TI - Chronic immune thrombocytopenic purpura-who needs medication? AB - Chronic ITP (immune thrombocytopenic purpura; now defined as duration of more than 12 months) is not always associated with significant bleeding problems so that most children and adults can be managed expectantly with no medication unless surgery, accidents or other pathology mandate it. A cut-off platelet count of 30 x 10(9)/l divides a group with no increased mortality from those whose risk is greater and in whom medication is usually appropriate. There is increasing recognition of long-term morbidity and mortality associated with immune suppression induced by medication and more recently new concerns have arisen about the long-term vascular complications of splenectomy. A more conservative approach to medication is warranted in many patients with chronic ITP. PMID- 20309690 TI - Future research in ITP: an ICIS consensus. AB - While much has been learned about the basic immunology and clinical characteristics of immune thrombocytopenia, many important questions remain with regard to pathogenesis, disease progression, identification of novel therapeutic targets and approaches, and clinical trials that rationalize and optimize use of existing therapies. The answers to these questions are likely to impact our understanding of the pathogenesis and therapeutic targets of autoimmune disease in general. PMID- 20309691 TI - Genetic studies in pediatric ITP: outlook, feasibility, and requirements. AB - The genomic revolution in medicine has not escaped attention of clinicians and scientists involved in medical management and research studies of immune thrombocytopenic purpura (ITP). In principle, ITP biology and care will benefit greatly from modern methods to understand the patterns of gene expression and genetic markers associated with fundamental parameters of the disease including predictors of remission, risk factors for severity, determinants of response to various therapies, and possibly biological sub-types. However, applying modern genetics to ITP carries severe challenges: (a) Achieving adequate sample sizes is a fundamental problem because ITP is rare (and in pediatric ITP, chronic cases constitute only about one fourth of the total); (b) familial transmission of childhood ITP is so rare that a convincing pedigree requires consideration of other immunologic or hematologic disorders; (iii) ITP is probably biologically heterogeneous, based on clinical observations, immunological studies, and animal models. Here we review the advantages and disadvantages of potential genetic approaches. Sufficient information is available to set reasonable bounds on which genetic analyses of ITP are feasible and how they are most likely to be accomplished. The highest priority is for accurate phenotypes to compare to genetic analyses. Several registries worldwide hold promise for accomplishing this goal. PMID- 20309692 TI - MDR1 C2005T polymorphism changes substrate specificity. AB - PURPOSE: The current study is to determine the alterations of efflux transport activity to Rh123 and sensitivity to anticancer agents mediated by a MDR1 C2005T polymorphism. METHODS: Expressions of mRNA and protein of MDR1 were measured by real-time PCR and immunoblotting, respectively, and localization of P glycoprotein (P-gp) by confocal microscopy. Cell cytotoxicity and efflux transport activity were determined by MTT and Rh123 transepithelial permeability assay, respectively. RESULTS: MDR1 C2005T polymorphism did not affect the expression level of the MDR1 mRNA and protein and had no effect on the trafficking of P-gp to plasma membrane. A cytotoxicity study showed that MDR1wt and MDR1 (2005T) cells exhibited similar resistance, as measured by IC(50) values, to vinblastine (30.3 +/- 2.5 vs. 32.5 +/- 1.7 nM) and vincristine (104.1 +/- 1.9 vs. 110.3 +/- 3.5 nM). However, MDR1 (2005T) cells were less resistant to paclitaxel (28.2 +/- 2.1 vs. 91.8 +/- 3.5 nM; P < 0.05) and etoposide (119.7 +/- 6.5 vs. 546.8 +/- 9.5 nM; P < 0.05). The apparent transepithelial permeability ratios of Rh123 in MDR1 (wt) and MDR1 (2005T) cells were 2.12 +/- 0.46 and 3.64 +/- 0.78 (P < 0.05), respectively. CONCLUSIONS: The MDR1 C2005T polymorphism alters the transepithelial permeability of a fluorescent substrate and sensitivity to select cytotoxic agents, which may influence drug disposition and the therapeutic efficacy of some P-gp substrates. PMID- 20309693 TI - Hydroxychloroquine improves dry eye symptoms of patients with primary Sjogren's syndrome. AB - The objective of the study is to investigate the effect of hydroxychloroquine (HCQ) on subjective and objective parameters of dry eye in patients with primary Sjogren's disease and to evaluate the association of tear fluid B-cell activating factor (BAFF) level with the response. Thirty-two patients with primary Sjogren's disease were enrolled in this prospective study. All patients included in the study completed at least a 48-month run-in period of using hydroxychloroquine. Patients were then instructed to drop the treatment for 3 months. Baseline and post cessation of treatment (baseline and 3 months) evaluations included, subjective symptom scoring, fluorescein and lissamine green staining, Schirmer's test, tear break-up time (BUT) and tear fluid BAFF assessments. Significant worsening was observed in, tear break up-time (TBUT) (7.9 +/- 3.4 vs. 5.9 +/- 2.9, P < 0.001) lissamine green of staining of the ocular surface (1.3 +/- 0.9 vs. 1.8 +/- 0.8, P < 0.01) and corneal fluorescein staining scores (2.2 +/- 2.1 vs. 4.6 +/- 3.3, P < 0.003) between on and off HCQ treatment, respectively. Similarly, gritty sensation and burning sensation were significantly changed at week 12 compared to baseline evaluation (1.18 +/- 1.02 vs. 1.7 +/- 1.05, P < 0.007 and 1.1 +/- 1.0 vs. 1.6 +/- 1.2, P < 0.0, respectively). Disease duration significantly correlated with baseline OSDI (r = 0.38, P < 0.04) and the average daily use of artificial tears (r = 0.36, P < 0.04). The mean BAFF levels were 0.8 +/- 0.5 and 4.0 +/- 0.7 ng/ml for baseline and week 12 evaluation, respectively (P < 0.0001). The results of this study suggest that HCQ may alleviate symptoms and signs of dry eye in pSS and decreases tear fluid BAFF levels. PMID- 20309694 TI - Effects of micronutrient antioxidants (alpha-tocopherol and ascorbic acid) on skin thickening and lung function in patients with early diffuse systemic sclerosis. AB - To assess the effects of alpha-tocopherol and ascorbic acid on skin thickening and lung function in patients with early diffuse systemic sclerosis (SSc), thirteen patients with early diffuse SSc, with positive anti-topoisomerase-I antibody, high skin thickening progression rate (STPR >= 12/year) and decreased lung diffusing capacity (DLCO <= 75%) were included in this study. Patients were randomized into two subgroups: Subgroup A-six patients, treated with intravenous cyclophosphamide (CyP) (500 mg/m(2) of body surface monthly) and antioxidants (alpha-tocopherol 400 IU/day and ascorbic acid 1,000 mg/day), and Subgroup B seven patients, who received CyP without antioxidants. In both subgroups, effects of treatment on skin thickening and lung function were evaluated by comparison of the modified Rodnan skin score (MRSS), STPR, forced vital capacity (FVC), transfer-factor (DLCO) and diffusing coefficient for carbon monoxide (DLCO/VA) at baseline and 1 month after the sixth pulse of CyP. The mean MRSS did not change from baseline to the end of the follow-up in subgroup A (15.7 vs. 16.4, P = 0.50), but it increased significantly in subgroup B (17.9 vs. 23.6, P = 0.03). Although the mean STPR decreased notably in both subgroups of patients (in subgroup A-from 18.9/year to 2.2/year, P = 0.03, and in subgroup B-from 17.5/year to 8.6/year, P = 0.03), the mean STPR at the end of the treatment period was significantly lower in subgroup A (2.2/year vs. 8.6/year, P = 0.04). The mean value of FVC did not change either in subgroup A (91.0-87%, P = 0.2) or in subgroup B (from 101.2 to 99.7%, P = 0.7). Parameters of lung diffusing capacity improved somewhat in subgroup A (DLCO from 55.7 to 62.0% and DLCO/VA from 68.7 to 74.2%) and decreased in subgroup B (DLCO from 66.2 to 60.6% and DLCO/VA from 76.9 to 71.6%), but differences were not statistically significant. After 6 months of therapy, patients treated with CyP and antioxidants had a significantly lower STPR, compared to patients treated with CyP only. Lung function parameters remained stable in both subgroups. However, lung diffusing capacity improved slightly, without statistical significance, in patients treated with CyP and antioxidants, and it deteriorated in patients without antioxidants. PMID- 20309695 TI - [Acute bilateral shoulder pain as initial presentation of ochronosis: a case report and literature review]. AB - Ochronosis is a rare genetic metabolic disorder resulting from a constitutional lack of homogentisic acid oxidase and subsequent accumulation of its substrate causing destruction of connective tissues with various systemic abnormalities. Typical musculoskeletal symptoms are arthropathy and low back pain and stiffness. Arthropathy primarily affects knee and hip joints, but shoulders are less frequently involved. We describe a case of ochronosis initially presented as acute bilateral shoulder pain. Review of literature with respect to the etiology, natural course of the disease, differential diagnosis and management was made. PMID- 20309696 TI - [The role of TNF-alpha as pain mediator]. AB - Tumor necrosis factor (TNF)-alpha is not only a proinflammatory mediator but also a pain mediator. Numerous nociceptors express the TNF receptors 1 and 2. By a direct action at the nociceptor TNF-alpha is involved in the generation and maintenance of inflammation-related pain. PMID- 20309698 TI - [The G-DRG System 2009--relevant changes for rheumatology]. AB - The following article presents the major general and specific changes in the G DRG system, in the classification systems for diagnoses and procedures as well as for the billing process for 2010. Since the G-DRG system is primarily a tool for the redistribution of resources, every hospital needs to analyze the economic effects of the changes by applying the G-DRG transition-grouper to its own cases. Depending on their clinical focus, rheumatological departments may experience positive or negative consequences from the adjustments. In addition, relevant current case law is considered. PMID- 20309697 TI - [Capillaroscopy. Procedure and nomenclature]. AB - Capillaroscopy has high diagnostic and prognostic value in autoimmune connective tissue diseases, in particular systemic sclerosis (SSc). Our working group has developed a consensus on nomenclature, technical equipment, procedure, and diagnostic interpretation of results. The following are required: binocular microscopes with at least 20-/50- and 160-/200-fold magnification and digital archiving. Documentation of defined findings is mandatory. The simultaneous occurrence of, e.g. caliber variations, ectasia, ramifications, elongation (length > 350 microm), torsion (at least two crossing segments per capillary loop), sludge, hemorrhage, and edema is of pathological significance. The isolated occurrence of bushy capillaries (multiple ramifications), thrombosis, giant capillary (capillary lumen > 50 microm), and avascular areas also indicates disease. The latter two findings are highly specific for SSc. Other findings are consistent with connective tissue diseases. These standardized definitions increase quality and comparability of nailfold capillaroscopy in Germany. PMID- 20309699 TI - [Immunomodulatory therapy improves quality of life with rheumatoid arthritis]. AB - Pain, fatigue as well as functional and social impairments reduce the health related quality of life in rheumatoid arthritis patients. Using numeric evaluations and qualitative questionnaires, it could be shown in both controlled drugs trials and in practice registries that modern drug therapy achieves an improvement in terms of quality of life (as well as in other patient-related treatment results). However, the improvements often do not achieve even the average quality-of-life levels seen in healthy people. PMID- 20309700 TI - [Health-related quality of life (HRQoL) in rheumatoid arthritis]. AB - In order to measure therapeutic effects or assess disease course, outcomes measurement parameters are commonly used in patients with rheumatoid arthritis. From the patient's perspective, possibly the most important outcome measurement parameter is quality of life (QoL). QoL may be defined in terms of "health status" and "functioning in daily life". According to the WHO, quality of life is defined as the satisfaction of a patient/person with their situation in terms of health status and their ability to function in daily life. Since assessing QoL makes sense only from the patient's perspective, generic or disease-specific questionnaires are usually used. For rheumatoid arthritis, multiple questionnaires which can be used in a routine clinical setting are available. In addition, QoL is a highly subjective concept and can depend on a variety of individual factors. Thus, measurement of QoL using the profiles and indices of common instruments cannot fully account for an individual's perspective. PMID- 20309701 TI - [Spondyloarthritis and quality of life]. AB - To measure the disease activity of spondyloarthritides (SpA), quality of life is assessed in addition to inflammation and functional impairment. To measure quality of life in ankylosing spondylitis (AS), the generic measurement instruments SF-36, SF-12 and EQ-5D are available in German, whereby the SF-36 is the instrument primarily used in clinical investigations. Compared to the normal population, AS patients experience a reduced quality of life. In woman and patients with a poor educational background, quality of life was particularly reduced.Measuring quality of life is also a generally recognised part of evaluating psoriasis arthritis (PsA), for which only SF-36 and EQ-5D are available in German-speaking countries. The instrument most frequently used in clinical studies is SF-36. The quality of life in PsA patients, in terms of both physical and mental components, was found to be significantly lower than in the normal population. Although PsA patients shared a similar reduction in quality of life to AS patients, they nevertheless enjoyed a better quality of life than rheumatoid arthritis patients. PMID- 20309702 TI - [The significance of health-related quality of life in systemic vasculitides]. AB - Systemic vasculitides are a heterogenous group of chronic relapsing diseases. Initial data show that health-related quality of life (HRQoL) from the patient's perspective is reduced on all levels (physical, social and emotional). These studies suggest that generic questionnaires do not encompass all relevant and important levels of HRQoL in vasculitis. Moreover, data indicate that tiredness (fatigue) and reduced energy levels play a significant role. This article presents an overview of the existing literature. PMID- 20309703 TI - [Measuring quality of life in rheumatic disease. A critical appraisal]. AB - The term quality of life (QoL) has been introduced to account for relevant non clinical endpoints and the integration of patients' perspectives into treatment evaluation, amongst others. However, QoL is not a uniform, consistent scientific concept but an equivocal generic term for a field of interest. It can relate to such diverse aspects as living conditions, functioning, perception or appraisal of health-related states or general aspects of life. Any assessment of QoL must necessarily exclude relevant facets and assume comparability of basic important life themes in specific groups of people. Widespread instruments for QoL assessment in rheumatology, e.g. SF-36, EQ-5D or the Nottingham Health Profile, represent different QoL concepts (profiles vs. indices). However, they have in common a societal ideal of a physically capable, mentally healthy, socially integrated and functionally competent person. Before an assessment of QoL the aims of an assessment and the concepts of interest should be specified. PMID- 20309704 TI - [Quality of life in rheumatic diseases]. PMID- 20309705 TI - Comment on "Hybrid computational phantoms for medical dose reconstruction" by Bolch et al. PMID- 20309706 TI - Tissue and data archives from irradiation experiments conducted at Argonne National Laboratory over a period of four decades. AB - Irradiation experiments conducted on dogs and mice at Argonne National Laboratory, IL between 1952 and 1992 led to creation of archives of paraffin embedded tissues accompanied by extensive datasets with gross pathology and histopathology information. Over the past 40 years, these data were investigated computationally, using different statistical approaches. Embedded tissues are used to this day as a source of genomic and mitochondrial DNA for quantitative PCR amplification. Data and paraffin block sections are available upon request interested researchers should visit the Websites http://janus.northwestern.edu/dog_tissues/introduction.php for dog and http://janus.northwestern.edu/janus2/index.php for mouse archive. PMID- 20309707 TI - Temporal trends in childhood leukaemia incidence following exposure to radioactive fallout from atmospheric nuclear weapons testing. AB - Notably raised rates of childhood leukaemia incidence have been found near some nuclear installations, in particular Sellafield and Dounreay in the United Kingdom, but risk assessments have concluded that the radiation doses estimated to have been received by children or in utero as a result of operations at these installations are much too small to account for the reported increases in incidence. This has led to speculation that the risk of childhood leukaemia arising from internal exposure to radiation following the intake of radioactive material released from nuclear facilities has been substantially underestimated. The radionuclides discharged from many nuclear installations are similar to those released into the global environment by atmospheric nuclear weapons testing, which was at its height in the late-1950s and early-1960s. Measurements of anthropogenic radionuclides in members of the general public resident in the vicinity of Sellafield and Dounreay have found levels that do not differ greatly from those in persons living remote from nuclear installations that are due to ubiquitous exposure to the radioactive debris of nuclear weapons testing. Therefore, if the leukaemia risk to children resulting from deposition within the body of radioactive material discharged from nuclear facilities has been grossly underestimated, then a pronounced excess of childhood leukaemia would have been expected as a consequence of the short period of intense atmospheric weapons testing. We have examined childhood leukaemia incidence in 11 large-scale cancer registries in three continents for which data were available at least as early as 1962. We found no evidence of a wave of excess cases corresponding to the peak of radioactive fallout from atmospheric weapons testing. The absence of a discernible increase in the incidence of childhood leukaemia following the period of maximum exposure to the radioactive debris of this testing weighs heavily against the suggestion that conventional methods are seriously in error when assessing the risk of childhood leukaemia from exposure to man-made radionuclides released from nuclear installations. PMID- 20309708 TI - Muscle ceramide content in man is higher in type I than type II fibers and not influenced by glycogen content. AB - Human muscle is studied during glycogen depletion and repletion to understand the influence of exercise and muscle glycogen on total ceramide content. In addition, fiber-type-specific ceramide storage is investigated. Ten healthy males (26.4 +/- 0.9 years, BMI 24.4 +/- 0.7 kg m(-2) and VO2max 57 +/- 2 mL O2 min(-1) kg(-1)) participated in the study. On the first day, one leg was glycogen-depleted (DL) by exhaustive intermittent exercise followed by low carbohydrate diet. Next day, in the overnight fasted condition, muscle biopsies were excised from vastus lateralis before and after exhaustive exercise from both DL and control leg (CL). Muscle glycogen was analyzed biochemically and total muscle ceramide content by 2D quantitative lipidomic approach. Furthermore, fiber-type ceramide content was determined by fluorescence immunohistochemistry. Basal muscle glycogen was decreased (P < 0.05) with 50 +/- 6% in DL versus CL. After exhaustive exercise, muscle glycogen was similar in CL and DL 139 +/- 38 and 110 +/- 31 mmol kg(-1), respectively. Total muscle ceramide 58 +/- 1 pmol mg(-1) was not influenced by glycogen or exercise. Ceramide content was consistently higher (P < 0.001) in type I than in type II muscle fibers. In conclusion, human skeletal muscle, ceramide content is higher in type I than in type II. Despite rather large changes in muscle glycogen induced by prior depletion, exercise to exhaustion and repletion, total muscle ceramide concentration remained unchanged. PMID- 20309709 TI - Task conflict effect in task switching. AB - A part of action preparation is deciding what the relevant task is. This task decision process is conceptually separate from response selection. To show this, the authors manipulated task conflict in a spatial task-switching paradigm, using conflict stimuli that appeared during trials with univalent targets (affording 1 task). The conflict stimuli afforded task identity because they were used as task cues with bivalent targets (affording 2 tasks) that were intermixed with the univalent targets. Thus, for univalent targets, irrelevant stimuli either caused low task conflict or high task conflict. In three experiments, the authors found poorer performance in high task conflict trials than in low task conflict trials. Task conflict was introduced during target appearance (Experiment 1) or task preparation (Experiments 2 and 3). In the latter case, the task conflict effect decreased with increasing task preparation time showing that task preparation involves task decision. PMID- 20309711 TI - Predictors of residual symptoms in lower extremities after decompression surgery on lumbar spinal stenosis. AB - Leg pain/numbness and gait disturbance, two major symptoms in the lower extremities of lumbar spinal stenosis (LSS), are generally expected to be alleviated by decompression surgery. However, the paucity of information available to patients before surgery about specific predictors has resulted in some of them being dissatisfied with the surgical outcome when the major symptoms remain after the procedure. This prospective, observational study sought to identify the predictors of the outcome of a decompression surgery: modified fenestration with restorative spinoplasty. Of 109 consecutive LSS patients who underwent the decompression surgery, 89 (56 males and 33 females) completed the 2 year follow-up. Both leg pain/numbness and gait disturbance determined by the Japanese Orthopedic Association scoring system were significantly improved at 2 years after surgery compared to those preoperative, regardless of potential predictors including gender, preoperative presence of resting numbness in the leg, drop foot, cauda equina syndrome, degenerative spinal deformity or myelographic filling defect, or the number of decompressed levels. However, 27 (30.3%) and 13 (14.6%) patients showed residual leg pain/numbness and gait disturbance, respectively. Among the variables examined, the preoperative resting numbness was associated with residual leg pain/numbness and gait disturbance, and the preoperative drop foot was associated with residual gait disturbance, which was confirmed by logistic regression analysis after adjustment for age and gender. This is the first study to identify specific predictors for these two remaining major symptoms of LSS after decompression surgery, and consideration could be given to including this in the informed consent. PMID- 20309712 TI - Comparison of enlargement of the spinal canal after cervical laminoplasty: open door type and double-door type. AB - The purpose of this study was to compare the degree of enlargement of the spinal canal between two methods of cervical laminoplasty (open-door laminoplasty and double-door laminoplasty) and to determine their appropriate surgical indications based on the results. Tension-band laminoplasty (TBL, one method of open-door type) was performed in 33 patients and double-door laminoplasty (DDL) in 20 patients. The operation level ranged from C2 to C7 in all patients. The width of the spinal canal and the inclination angle of the lamina at the C5 and C6 levels were measured using a computer software program (Image J) and pre- and postoperative CT films. Concerning the degree of enlargement of the spinal canal, the mean expansion ratio at the C5 level was 148.9% in TBL and 148.2% in DDL, and there was no significant difference between them. However, at the C6 level, it was 159.0% in TBL and 140.3% in DDL, which was significantly larger in TBL than DDL (p < 0.05). The increase of inclination angle of the lamina was 11.0 degrees in TBL and 19.0 degrees in DDL at the C5 level, and 9.2 degrees in TBL and 19.3 degrees in DDL at the C6 level. At both the C5 and C6 levels, it was significantly larger in DDL than TBL (p < 0.0001). In conclusion, the appropriate surgical indications of TBL were considered to be (1) cervical spondylotic myelopathy (CSM) combined with hemilateral radiculopathy, (2) severe prominence of ossification of the posterior longitudinal ligament (OPLL), and (3) patients with tiny spinous processes who cannot undergo DDL. Those of DDL were considered to be (1) usual CSM, (2) small and slight prominence of OPLL, (3) CSM combined with bilateral radiculopathy, and (4) cervical canal stenosis combined with instability necessitating posterior spinal instrumentation surgery. PMID- 20309713 TI - Larval stage Lymantria dispar microRNAs differentially expressed in response to parasitization by Glyptapanteles flavicoxis parasitoid. AB - MicroRNAs (miRNAs) are small RNA molecules that regulate gene expression by targeting messenger RNAs and causing cleavage or translation blockage. miRNAs induced after parasitization of the lepidopteran host Lymantria dispar by the parasitoid wasp Glyptapanteles flavicoxis, which introduces a polydnavirus and other parasitoid factors, were examined to identify induced miRNAs that might regulate host genes and contribute to host immunosuppression and other effects. miRNA profiling of parasitized larval hemocytes versus non-parasitized ones by microarray hybridization to mature insect and virus miRNAs identified 27 differentially expressed miRNAs after parasitization. This was confirmed by real time relative qPCR for insect miRNAs (dme-mir-1, -8, -14, -184, -276, -277, -279, -289, -let-7) using miRNA-specific TaqMan assays. Certain cellular miRNAs were differentially expressed in larval tissues, such as the potentially developmentally linked mir-277, signifying a need for functional studies. PMID- 20309714 TI - Journal of Artificial Organs 2009: the year in review. PMID- 20309715 TI - Synchronous collision malignant melanoma and adenocarcinoma of the rectum. AB - "Collision tumors" consist of two independent but coexisting tumors. This uncommon situation might be easily mistaken for a composite tumor where one histogenetic event originates from two apparently distinct neoplasms. Colorectal collisions are particularly unusual; here, we report the exceedingly rare case of a 61-year-old man with malignant melanoma and adenocarcinoma colliding in the rectum. Collision tumors have an idiopathic pathophysiology and in fact "accidental meeting" is accepted by many authors. This article discusses the concepts about cancer development, which are overlooked by this hypothesis, another theory to explain that this rare occurrence involves microenvironment changes. PMID- 20309716 TI - Correction of end colostomy prolapse using a curved surgical stapler, performed under sedation. AB - Acute stoma prolapse most commonly occurs following emergency surgery, frequently in patients with significant medical co-morbidities. Correction often requires re laparotomy and resiting of the stoma, placing an already frail patient at risk of further morbidity. An elderly patient experienced an end colostomy prolapse 14 days following emergency laparotomy. A novel technique was employed using the CONTOUR curved stapling device to excise the prolapsed segment, under a brief period of intravenous sedation, thereby avoiding the sequelae of general anaesthetic. No complications were experienced, and the patient was deemed fit for discharge 5-days post re-intervention. PMID- 20309717 TI - Transvaginal sacrospinous rectopexy: initial clinical experience. AB - BACKGROUND: There is a wide range of surgical procedures available to treat rectal prolapse that differ in approach as well as in principle. The current perineal approaches available involve mucosal or full thickness resection. There are currently no accepted procedures combining rectal fixation without resection using the perineal approach. We present our initial report of transvaginal sacrospinous rectopexy for the treatment of rectal prolapse. METHODS: A longitudinal incision was made in the posterior wall of the vagina. The rectum and sacrospinous ligament were identified. Two sutures were placed in the sacrospinous ligament and brought through a piece of Surgisis mesh previously anchored to the anterior surface of the rectum. This was performed bilaterally. These sutures were tied to complete the rectal suspension, and the posterior wall of the vagina was closed. RESULTS: Transvaginal sacrospinous rectopexy was performed in all seven cases. In the first two cases, a Delorme procedure was performed concurrently. Two patients had rubber band ligation for symptomatic internal hemorrhoids, one patient had a sphincter plication, and one patient had an anal encirclement procedure with Surgisis. Six of the seven patients had concomitant urologic procedures. The average operative time was 163 min, and the average blood loss was 107 mL. None of the cases required conversion to an open procedure. There was one full thickness recurrence at 18 weeks. CONCLUSION: Transvaginal sacrospinous rectopexy is a safe, minimally invasive, technically feasible technique for the treatment of rectal prolapse. PMID- 20309718 TI - Cyanidin-3-O-beta-glucoside inhibits LPS-induced expression of inflammatory mediators through decreasing IkappaBalpha phosphorylation in THP-1 cells. AB - OBJECTIVE AND DESIGN: As a common phytochemical, cyanidin 3-O-beta-glucoside (C3G) has a role in inhibiting inflammatory mediators; however, its mechanism of action remains unclear. The purpose of this study was to explore the effect of C3G on lipopolysaccharide (LPS)-stimulated TNFalpha and IL-6 expression in the human monocyte/macrophage cell line THP-1, and to explore the mechanisms involved. METHODS: Differentiated THP-1 cells were treated with different concentrations of C3G (0.005, 0.05, 0.5,10 microM) in the absence or presence of 1 ng/mL LPS. mRNA expression levels were detected by real time PCR, and secretion of TNFalpha and IL-6, phosphorylated IkappaBalpha, and nuclear factor-kappa B (NF kappaB) P65 were monitored by ELISA or Western blotting analysis. The role of an inhibitor of IkappaBalpha phosphorylation, BAY 11-7082, in C3G inhibition of LPS induced cytokines expression was investigated. RESULTS: C3G (0.05-0.5 microM) treatment significantly inhibited LPS-stimulated TNFalpha and IL-6 mRNA expression and secretion of these proteins by THP-1 cells. Phosphorylation of IkappaBalpha and NF-kappaB nuclear translocation could be blocked by 0.5 microM C3G. BAY 11-7082 treatment abolished C3G-induced reduction of TNFalpha and IL-6. CONCLUSION: Our results suggest that C3G exerts its anti-inflammatory effect through inhibiting IkappaBalpha phosphorylation, thereby suppressing NF-kappaB activity in THP-1 cells. PMID- 20309719 TI - A prospective study of temozolomide plus thalidomide during and after radiation therapy for pediatric diffuse pontine gliomas: preliminary results of the Korean Society for Pediatric Neuro-Oncology study. AB - This prospective study was performed to determine the efficacy and safety of temozolomide (TMZ) plus thalidomide during and after radiation therapy (RT) in pediatric patients with newly diagnosed diffuse pontine glioma (DPG). Seventeen patients with pediatric DPG were enrolled between November 2004 and March 2008. The median age was eight years (range, 3-16 years); seven patients were male and ten were female. With the exception of one glioblastoma case, which was diagnosed via open biopsy, all diagnoses were established using neuroradiological studies. The authors used the Korean Society for Pediatric Neuro-Oncology (KSPNO)-A053 protocol. The mean follow-up period was 12 months (range, 8.5-25 months). Five patients were withdrawn from the study. The rates of response to treatment and survival were analyzed in 12 patients. Ten out of the 12 patients showed a partial response (PR), whereas one patient exhibited stable disease (SD) and another patient had progressive disease (PD). The tumor control rate was 92% (11/12) and the response rate was 83% (10/12). The median progression-free survival (PFS) of the 12 patients was 7.2 months (95% confidence interval (CI), 3.6-10.7). Six-month and twelve-month PFS were 58.3 and 16.7%, respectively. Overall survival (OS) was 12.7 months (95% CI, 10.4-15.1). One and two-year survival were 58.3 and 25%, respectively. The main adverse effect was hematological toxicity, with four patients exhibiting grade 3 or 4 toxicity. All patients tolerated the regimen well enough to continue the adjuvant chemotherapy. No Pneumocystis jiroveci pneumonia was noted. The TMZ plus thalidomide regimen was safe and tolerated well enough to be administered on an outpatient basis. Larger studies are required to demonstrate the efficacy of this regimen. PMID- 20309720 TI - The CXCR4 antagonist AMD3100 suppresses hypoxia-mediated growth hormone production in GH3 rat pituitary adenoma cells. AB - Pituitary adenomas produce the chemokine stromal cell-derived factor (SDF 1alpha/CXCL12) and its receptor, CXCR4. A recent study indicated that CXCL12 and CXCR4 are concomitantly up-regulated in hypoxia. The objective of this study was to analyze the molecular mechanism of hypoxia-mediated CXCR4 up-regulation and assess the effect of pharmacological inhibition of CXCR4 by the receptor blocker, AMD3100, on pituitary function. CXCR4 expression in pituitary adenoma tissues was determined by a tissue microarray analysis of 62 pituitary adenoma samples. CXCR4 expression was significantly elevated and positively correlated with Knosp grade in pituitary adenomas (P < 0.005), and was higher in macroadenoma and growth hormone (GH)-producing adenomas. Pre-operative serum GH levels were significantly correlated with CXCR4 levels in the microarray (P < 0.0001). The relative expression of genes/gene categories that were modulated by up-regulated CXCL12/CXCR4 signaling was determined by a comparative transcriptome analysis of wild-type and CXCR4-knockdown cells in normoxia and hypoxia using the rat GH producing and prolactin-producing pituitary adenoma cell line, GH3. Real-time reverse transcriptase-polymerase chain reaction analysis (RT-PCR) showed that CXCR4 mRNA expression in GH3 cells was increased by hypoxia (1% oxygen), and a cDNA microarray analysis revealed that inhibin beta-C expression was diminished. siRNA-mediated CXCR4 knockdown blocked the hypoxia-induced decrease in inhibin beta-C mRNA expression, as did inhibition of CXCR4 activity with AMD3100. An ELISA study demonstrated that GH secretion by wild-type GH3 cells was moderately enhanced by hypoxia and further potentiated by exposure to recombinant SDF 1alpha/CXCL12 protein. Conversely, hypoxia-induced GH secretion was reduced in CXCR4-silenced cells and in cells treated with the CXCR4 antagonist, AMD3100, notwithstanding the presence of SDF-1alpha/CXCL12 protein. These latter observations reflect the failure of hypoxia to suppress expression of inhibin beta-C in cells deficient in CXCR4 or in which CXCR4 signaling was blocked. Together, these results indicate that the SDF-1alpha/CXCL12-CXCR4 signaling pathway interfaces with the classical endocrine pathway to up-regulate GH production via suppression of inhibin beta-C. Because it blocks CXCR4 and prevents hypoxia-induced down-regulation of inhibin beta-C expression, AMD3100 has promise as a molecular-targeting agent in the treatment of GH-producing adenomas. PMID- 20309721 TI - Metnase/SETMAR: a domesticated primate transposase that enhances DNA repair, replication, and decatenation. AB - Metnase is a fusion gene comprising a SET histone methyl transferase domain and a transposase domain derived from the Mariner transposase. This fusion gene appeared first in anthropoid primates. Because of its biochemical activities, both histone (protein) methylase and endonuclease, we termed the protein Metnase (also called SETMAR). Metnase methylates histone H3 lysine 36 (H3K36), improves the integration of foreign DNA, and enhances DNA double-strand break (DSB) repair by the non-homologous end joining (NHEJ) pathway, potentially dependent on its interaction with DNA Ligase IV. Metnase interacts with PCNA and enhances replication fork restart after stalling. Metnase also interacts with and stimulates TopoIIalpha-dependent chromosome decatenation and regulates cellular sensitivity to topoisomerase inhibitors used as cancer chemotherapeutics. Metnase has DNA nicking and endonuclease activity that linearizes but does not degrade supercoiled plasmids. Metnase has many but not all of the properties of a transposase, including Terminal Inverted Repeat (TIR) sequence-specific DNA binding, DNA looping, paired end complex formation, and cleavage of the 5' end of a TIR, but it cannot efficiently complete transposition reactions. Interestingly, Metnase suppresses chromosomal translocations. It has been hypothesized that transposase activity would be deleterious in primates because unregulated DNA movement would predispose to malignancy. Metnase may have been selected for in primates because of its DNA repair and translocation suppression activities. Thus, its transposase activities may have been subverted to prevent deleterious DNA movement. PMID- 20309722 TI - Phenotypic variability in five Aceria spp. (Acari: Prostigmata: Eriophyoidea) inhabiting Cirsium species (Asteraceae) in Serbia. AB - From about 250 Cirsium spp., only two Aceria spp. (Acari: Eriophyoidea) have been described, Aceria anthocoptes (Nal.) and Aceria cirsii Pet. B. & Shi. Host specificity, which generally characterizes eriophyoid mites, potentially leads to speciation, so we may expect more than two Aceria spp. and/or other infraspecific taxa. Furthermore, studies on host-related variability in the morphology of Aceria mites are generally lacking. The purpose of this study was to investigate quantitative morphological traits of five Aceria populations inhabiting five Cirsium spp. in Serbia. MANOVA analysis revealed significant differences in 23 commonly used morphological traits as well as four additional traits related to the prodorsal shield design. In addition, the most important qualitative traits using scanning electron microphotographs were studied in order to clarify phenotypic differences among five Aceria spp. Discriminant analysis identified eight traits that significantly differentiate five populations. UPGMA cluster analysis of the squared Mahalanobis distances indicates that A. cirsii was morphologically the most divergent, while A. anthocoptes populations from Cirsium arvense and Aceria sp. from Cirsium heterophyllum were isolated from the branch clustering Aceria spp. populations from Cirsium eriophorum and Cirsium creticum. Analysis of qualitative traits using SEM confirmed results obtained from the analysis of morphometric features. PMID- 20309723 TI - The application of lambda-cyhalothrin in tick control. AB - In recent years, in urban areas of Novi Sad, unique ecological conditions, specific floristic and faunistic composition and poor habits of citizens in sense of public health, facilitate the development and maintenance of ticks. Regarding the importance of ticks as vectors of severe human and animal diseases, complex and detailed studies are conducted with an aim to find the most efficient methods for tick control. Two tick species, Ixodes ricinus and Dermacentor marginatus, were identified during a 3-year period on the territory of Municipality of Novi Sad. During 2006, the efficacy of the pyrethroid lambda-cyhalothrin in tick control varied from 60.7 to 100%. The highest efficacy recorded in 2007 was 92.3%. The efficacy of lambda-cyhalothrin in 2008 varied from 39.1 to 100%. Lambda-cyhalothrin showed high efficacy in tick control at localities which were improved before the application (mowed, litter removed, abundance control and euthanasia of abandoned cats and dogs). The results of this research indicate that lambda-cyhalothrin has a toxic effect on ticks and could be used as efficient acaricide for tick control, although its efficacy depends on formulation, terrain features and methods of application. PMID- 20309724 TI - Nepali concepts of psychological trauma: the role of idioms of distress, ethnopsychology and ethnophysiology in alleviating suffering and preventing stigma. AB - In the aftermath of a decade-long Maoist civil war in Nepal and the recent relocation of thousands of Bhutanese refugees from Nepal to Western countries, there has been rapid growth of mental health and psychosocial support programs, including posttraumatic stress disorder treatment, for Nepalis and ethnic Nepali Bhutanese. This medical anthropology study describes the process of identifying Nepali idioms of distress and local ethnopsychology and ethnophysiology models that promote effective communication about psychological trauma in a manner that minimizes stigma for service users. Psychological trauma is shown to be a multifaceted concept that has no single linguistic corollary in the Nepali study population. Respondents articulated different categories of psychological trauma idioms in relation to impact on the heart-mind, brain-mind, body, spirit, and social status, with differences in perceived types of traumatic events, symptom sets, emotion clusters and vulnerability. Trauma survivors felt blamed for experiencing negative events, which were seen as karma transmitting past life sins or family member sins into personal loss. Some families were reluctant to seek care for psychological trauma because of the stigma of revealing this bad karma. In addition, idioms related to brain-mind dysfunction contributed to stigma, while heart-mind distress was a socially acceptable reason for seeking treatment. Different categories of trauma idioms support the need for multidisciplinary treatment with multiple points of service entry. PMID- 20309725 TI - Primary peritoneal and ovarian cancers: an epidemiological comparative analysis. AB - We performed case-control analyses using data from the North Carolina Ovarian Cancer Study to determine risk factors that distinguish primary peritoneal cancer (PPC) from epithelial ovarian cancer (EOC). Our risk factor analyses were restricted to invasive serous cancers including 495 EOC cases, 62 PPC cases and 1,086 control women. Logistic regression analyses were used to calculate adjusted odds ratios and 95% confidence intervals for risk factor associations. Although many case-control associations for the invasive serous PPC cases were similar to those of the invasive serous EOC cases, some differences were observed including a twofold increase in risk of invasive serous PPC in women who were >or=35 years at last pregnancy, whereas a decreased risk was observed for invasive serous EOC risk. We could not confirm a previous report of an association between tubal ligation and PPC, a factor consistently associated with a decreased risk of EOC. The difference in the risk factor associations between invasive serous PPC and EOC cancers suggests divergent molecular development of peritoneal and ovarian cancers. A larger study to determine risk factors for invasive serous PPC is warranted. PMID- 20309726 TI - Anatomical mysteries. PMID- 20309727 TI - Effects of systemic nicotine, alcohol or their combination on cholinergic markers in the frontal cortex and hippocampus of rat. AB - Acute alcohol (Alc) intoxication has been shown to decrease choline acetyltransferase (ChAT) in the rat brain. The present study extends that finding by examining the effects of nicotine (Nic), Alc, and their combination on ChAT and acetylcholinesterase (AChE) in the frontal cortex and hippocampus of rat. The samples were collected at 30 and 120 min after intraperitoneal administration of saline (0.9%, control), Nic (1 mg/kg), Alc (1 g/kg), and Nic + Alc and analyzed by RT-PCR, Western blot and colorimetry. Alc alone considerably reduced ChAT mRNA expression, whereas Nic alone decreased AChE mRNA expression. In contrast, Nic + Alc exposure had resulted in no significant change in the parameters. These findings are consistent with the results of the Western blot and AChE activity analysis. The results, therefore, indicate that Nic and Alc alone may interact with the central cholinergic system. This interactive effect may contribute to a frequent association of tobacco and Alc consumption. PMID- 20309728 TI - Glutamate differently modulates metabotropic glutamate receptors in neuronal and glial cells. AB - Glutamate is an excitatory neurotransmitter implicated in learning and memory processes, but at high concentrations it acts as an excitotoxin causing degeneration and neuronal death. The aim of this work was to determine the excitotoxic effect of glutamate and the regulation of metabotropic glutamate receptors (mGluR) during excitotoxicity in neurons and C6 glioma cells. Results show that glutamate causes excitotoxic damage only in cortical neurons. Loss of cell viability in neurons was glutamate concentration- and time-dependent. Total mGluR levels were significantly reduced in these cells when exposed to glutamate. However, in C6 cells, which have been used as a model of glial cells, these receptors were regulated in a biphasic manner, decreased after 6 h, and increased after 24/48 h of treatment. Results show a cell dependent mGluR regulation by glutamate exposure which could mediate the vulnerability or not to glutamate mediated excitotoxicity. PMID- 20309730 TI - Computational investigation of the delamination of polymer coatings during stent deployment. AB - Recent advances in angioplasty have involved the application of polymer coatings to stent surfaces for purposes of drug delivery. Given the high levels of deformation developed in the plastic hinge of a stent during deployment, the achievement of an intact bond between the coating and the stent presents a significant mechanical challenge. Problems with coating delamination have been reported in recent experimental studies. In this paper, a cohesive zone model of the stent-coating interface is implemented in order to investigate coating debonding during stent deployment. Simulations reveal that coatings debond from the stent surface in tensile regions of the plastic hinge during deployment. The critical parameters governing the initiation of delamination include the coating thickness and stiffness, the interface strength between the coating and stent surface, and the curvature of the plastic hinge. The coating is also computed to debond from the stent surface in compressive regions of the plastic hinge by a buckling mechanism. Computed patterns of coating delamination correlate very closely with experimental images. This study provides insight into the critical factors governing coating delamination during stent deployment and offers a predictive framework that can be used to improve the design of coated stents. PMID- 20309729 TI - Chronic unpredictable stress before pregnancy reduce the expression of brain derived neurotrophic factor and N-methyl-D-aspartate receptor in hippocampus of offspring rats associated with impairment of memory. AB - To investigate the effect of stress before pregnancy on memory function and serum corticosterone (COR) levels, as well as the expression of brain-derived neurotrophic factor (BDNF), N-methyl-D-aspartate (NMDA) 2A (NR2A) and 2B (NR2B) receptors in the hippocampus of the offspring rats when they were 2 months postnatally. Adult female Sprague-Dawley (SD) rats were divided randomly into two groups: control group (n = 8) and chronic unpredictable stress (CUS) group (n = 12). All rats were tested in the open field test and sucrose intake test before and after CUS. The memory function of their offspring were tested in the Morris water maze. Serum COR levels were determined by using a standard radioimmunoassay kit. The expression of BDNF, NR2A and NR2B in the hippocampus of the offspring rats were studied by immunoreactivity quantitative analysis and real-time RT-PCR. (1) Following CUS, reduced open field test activity and decreased sucrose consumption were observed relative to controls. (2) The Morris water maze task demonstrated increased escape latency in the offspring rats of CUS group relative to controls (P < 0.01). No-platform probe testing showed reduced crossings for offspring of CUS relative to controls (P < 0.05). (3) CUS induced a significant increase in serum COR levels of the offspring rats (P < 0.01), but no difference was observed in the body or brain weight between the offspring of the two groups. (4) Immunoreactivity quantitative analysis shows that BDNF and NR2B in the offspring of CUS group was decreased in the CA3 and DG regions of the hippocampus compared to the control group offspring, but NR2A levels were not altered between the offspring of the two groups. (5) Real-time RT-PCR demonstrated that BDNF and NR2B mRNAs were significantly decreased in the offspring of the CUS group compared with the control group (P < 0.01). No significant difference in the levels of NR2A mRNA was detected between offspring of CUS and offspring of control groups. In our study, pregestational stress can increase serum corticosterone levels and reduce the expression of BDNF and NR2B in the hippocampus of offspring. These alterations are associated with impairment of memory in the adult offspring. These data suggest that, stress before pregnancy might have a profound influence on brain development of offspring, that may persist into and be manifested in adulthood. PMID- 20309731 TI - A comparative finite-element analysis of bone failure and load transfer of osseointegrated prostheses fixations. AB - An alternative solution to conventional stump-socket prosthetic limb attachment is offered by direct skeletal fixation. This study aimed to assess two percutaneous trans-femoral implants, the OPRA system (Integrum AB, Goteborg, Sweden), and the ISP Endo/Exo prosthesis (ESKA Implants AG, Lubeck, Germany) on bone failure and stem-bone interface mechanics both early post-operative (before bony ingrowth) and after full bone ingrowth. Moreover, mechanical consequences of implantation of those implants in terms of changed loading pattern within the bone and potential consequences on long-term bone remodeling were studied using finite-element models that represent the intact femur and implants fitted in amputated femora. Two experimentally measured loads from the normal walking cycle were applied. The analyses revealed that implantation of percutaneous prostheses had considerable effects on stress and strain energy density levels in bone. This was not only caused by the implant itself, but also by changed loading conditions in the amputated leg. The ISP design promoted slightly more physiological strain energy distribution (favoring long-term bone maintenance), but the OPRA design generated lower bone stresses (reducing bone fracture risk). The safety factor against mechanical failure of the two percutaneous designs was relatively low, which could be improved by design optimization of the implants. PMID- 20309732 TI - The effects of interfacial conditions and stem length on potential failure mechanisms in the uncemented resurfaced femur. AB - It is hypothesized that changes in stem length and implant-bone interfacial conditions would affect the mechanical environment within the uncemented resurfaced femur, thereby influencing potential short- and long-term failure mechanisms. This study is aimed at investigating the influence of changes in implant-bone interfacial conditions and stem length on eventual failure, using 3D FE models integrated with bone remodeling simulations. Musculoskeletal forces corresponding to normal walking and stair climbing were used as applied loading conditions. Sliding micromotions of 26-72 microm at the implant-bone interfaces for both the stem designs suggest bone ingrowth on the coated surface of the implant was likely. The initial risk of femoral neck fracture was less for the uncemented designs as compared to the cemented designs, irrespective of interfacial conditions and variation in stem length. For the uncemented variety, shortening the stem length provided only slight advantages (5%) with regard to strain shielding and bone remodeling. However, bone resorption was considerably higher when fully bonded interfaces were simulated. It may, therefore, be concluded that cementless fixation seems to be a viable alternative to cemented fixation, provided sufficient initial fixation and secondary stability through bone ingrowth into the coated surface of the implant can be achieved. PMID- 20309733 TI - The interface between generating renal tubules and a polyester fleece in comparison to the interstitium of the developing kidney. AB - An increasing number of investigations is dealing with the repair of acute and chronic renal failure by the application of stem/progenitor cells. However, accurate data concerning the cell biological mechanisms controlling the process of regeneration are scarce. For that reason new implantation techniques, advanced biomaterials and morphogens supporting regeneration of renal parenchyma are under research. Special focus is directed to structural and functional features of the interface between generating tubules and the surrounding interstitial space. The aim of the present experiments was to investigate structural features of the interstitium during generation of tubules. Stem/progenitor cells were isolated from neonatal rabbit kidney and mounted between layers of a polyester fleece to create an artificial interstitium. Perfusion culture was performed for 13 days in chemically defined Iscove's Modified Dulbecco's Medium containing aldosterone (1 x 10(-7) M) as tubulogenic factor. Recordings of the artificial interstitium in comparison to the developing kidney were performed by morphometric analysis, scanning and transmission electron microscopy. The degree of differentiation was registered by immunohistochemistry. The data reveal that generated tubules are embedded in a complex network of fibers consisting of newly synthesized extracellular matrix proteins. Morphometric analysis further shows that the majority of tubules within the artificial interstitium develops in a surprisingly close distance between 5 and 25 mum to each other. The abundance of synthesized extracellular matrix acts obviously as a spacer keeping generated tubules in distance. For comparison, the same principle of construction is found in the developing parenchyma of the neonatal kidney. Most astonishingly, scanning electron microscopy reveals that the composition of interstitial matrix is not homogeneous but differs along a cortico-medullary axis of proceeding tubule development. PMID- 20309734 TI - Cytokine antagonism reduces pain and modulates spinal astrocytic reactivity after cervical nerve root compression. AB - Relationships between nerve root compression, behavioral sensitivity, spinal cytokines, and glial reactivity are not fully defined for painful cervical nerve root compression. Spinal cytokines were quantified after mechanical root compression (10gf), root exposure to inflammatory chromic gut material (chr), the combination of both insults together (10gf + chr) or sham. TNFalpha and IL-1beta significantly increased at 1 h (p < 0.029). IL-1alpha was significantly increased over normal, sham and chr at 1 h following 10gf and over normal and sham after 10gf + chr (p < 0.048). By day 1, only IL-1beta after 10gf remained elevated over normal (p = 0.038). Accordingly, the soluble TNF receptor-1 (sTNFR1) and the IL-1 receptor antagonist (IL-1ra) were separately administered at early time points after each injury. With sTNFR1, behavioral sensitivity was significantly decreased for 7 days after both 10gf and 10gf + chr (p < 0.005). Treatment with IL-1ra significantly reduced sensitivity for 10gf + chr (p < 0.034) but not for 10gf. Sensitivity remained significantly elevated over sham at all time points (p < 0.044). Spinal astrocytic reactivity significantly decreased for both treatments after 10gf (p < 0.002); but, only IL-1ra following 10gf + chr significantly reduced astrocytic reactivity (p < 0.001). Early increases in spinal TNFalpha, IL-1beta, and IL-1alpha may induce pain, affect spinal astrocytic responses, and appear to have differential effects in mediating the behavioral hypersensitivity produced by different types of painful cervical radicular injuries. PMID- 20309735 TI - Unraveling changes in myocardial contractility during human fetal growth: a finite element analysis based on in vivo ultrasound measurements. AB - Knowledge of normal fetal heart (FH) performance and development is crucial for evaluating and understanding how various congenital heart lesions may modify heart contractility during the gestational period. However, since biomechanical models of FH are still lacking, structural approaches proposed to describe the mechanical behavior of the adult human heart cannot be used to model the evolution of the FH. In this paper, a finite element model of the healthy FH wall is developed to quantify its mechanical properties during the gestational period. An idealized thick-walled ellipsoidal shape was used to model the left ventricle (LV). The diastolic LV geometry was reconstructed from in vivo ultrasound measurements performed on 24 normal FHs between 20 and 37 weeks of gestation. An anisotropic hyperelastic constitutive law describing the mechanical properties of the passive and active myocardium was used. The evolution of the mechanical properties of the normal LV myocardium during fetal growth was obtained by successfully fitting the ejection fraction predicted by the model to in vivo measurements. We found that only the active tension varies significantly during the gestational period, increasing linearly from 20 kPa (at 20 weeks) to 40 kPa (at 37 weeks of gestation). We propose a possible explanation of the increasing force-generating ability of the myocardial tissue during fetal heart development based on a combination of myocyte enlargement, differentiation, and proliferation kinetics. PMID- 20309736 TI - A microfluidic imaging chamber for the direct observation of chemotactic transmigration. AB - To study the roles of nonmuscle myosin II (NM-II) during invasive cell migration, microfluidic migration chambers have been designed and fabricated using photo- and soft-lithography microfabrication techniques. The chamber consists of two channels separated by a vertical barrier with multiple bays of pores with widths varying from 6 microm to 16 microm, and lengths varying from 25 microm to 50 microm. The cells are plated in the channel on one side of the barrier while a chemoattractant is flowed through the channel on the other side of the barrier. In these chambers, cells can be observed with transmitted light or fluorescence optics while they chemotax through various sized pores that impose differential mechanical resistance to transmigration. As an initial test of this device, we compared breast-cancer cell chemotactic transmigration through different pore sizes with and without inhibition of NM-II. Two distinct rates were observed as cells attempted to pull their nucleus through the smaller pores, and the faster nuclear transit mode was critically dependent on NM-II motor activity. The ability to monitor cells as they chemotax through pores of different dimensions within a single experimental system provides novel information on how pore size affects cell morphology and migration rate, providing a dramatic improvement of imaging potential relative to other in vitro transmigration systems such as Boyden chambers. PMID- 20309737 TI - Assessment of metal contaminations leaching out from recycling plastic bottles upon treatments. AB - BACKGROUND, AIMS, AND SCOPE: Heavy metal contaminants in environment, especially in drinking water, are always of great concern due to their health impact. Due to the use of heavy metals as catalysts during plastic syntheses, particularly antimony, human exposure to metal release from plastic bottles has been a serious concern in recent years. The aim and scope of this study were to assess metal contaminations leaching out from a series of recycling plastic bottles upon treatments. METHODOLOGY: In this study, leaching concentrations of 16 metal elements were determined in 21 different types of plastic bottles from five commercial brands, which were made of recycling materials ranging from no. 1 to no. 7. Several sets of experiments were conducted to study the factors that could potentially affect the metal elements leaching from plastic bottles, which include cooling with frozen water, heating with boiling water, microwave, incubating with low-pH water, outdoor sunlight irradiation, and in-car storage. RESULTS: Heating and microwave can lead to a noticeable increase of antimony leaching relative to the controls in bottle samples A to G, and some even reached to a higher level than the maximum contamination level (MCL) of the US Environmental Protection Agency (USEPA) regulations. Incubation with low-pH water, outdoor sunlight irradiation, and in-car storage had no significant effect on antimony leaching relative to controls in bottle samples A to G, and the levels of antimony leaching detected were below 6 ppb which is the MCL of USEPA regulations. Cooling had almost no effect on antimony leaching based on our results. For the other interested 15 metal elements (Al, V, Cr, Mn, Co, Ni, Cu, As, Se, Mo, Ag, Cd, Ba, Tl, Pb), no significant leaching was detected or the level was far below the MCL of USEPA regulations in all bottle samples in this study. In addition, washing procedure did contribute to the antimony leaching concentration for polyethylene terephthalate (PET) bottles. The difference of antimony leaching concentration between washing procedure involved and no washing procedure involved (AC) was larger than zero for samples A to G. This interesting result showed that higher antimony concentration was detected in experiments with no washing procedures compared with those experiments with washing procedures. Our study results indicate that partial antimony leaching from PET bottles comes from contaminations on the surface of plastic during manufacturing process, while major antimony leaching comes from conditional changes. CONCLUSION: The results revealed that heating and microwaving enhance antimony leaching significantly in PET plastic bottles. Plastic bottle manufacturers should consider the contaminations during manufacturing process and washing bottles before first use was strongly recommended to remove those contaminants. PMID- 20309739 TI - Exploring the potential causes of the emergence of hospitalists: chicken vs. egg. PMID- 20309741 TI - Searching for pale, getting rickets. PMID- 20309740 TI - What is most important to patients when deciding about colorectal screening? AB - BACKGROUND: Colorectal cancer (CRC) screening can be administered through tests with varied characteristics and is a preference-sensitive decision. OBJECTIVE: To assess patient experiences with a Maximum Differences Scaling (MDS) tool for eliciting values about CRC screening test characteristics and determine whether patients vary in how they prioritize test characteristics and whether this variation relates to test preferences. DESIGN: MDS survey to elicit patients' values for characteristics related to fecal occult blood testing, sigmoidoscopy, colonoscopy, CT colonography and colon capsule endoscopy. PARTICIPANTS: 92 patients enrolled in primary care clinics at a VA hospital and associated university. RESULTS: Patients reported that the tool was easy to use (95%). On completion 62% would choose colonoscopy, 23% colon capsule endoscopy and 10% CT colonography. Of the attributes evaluated, patients valued sensitivity, risk of tear and need for a second test most. Sensitivity was more important to those choosing colonoscopy than those choosing other tests (median importance = 21.5 versus 19.6, p < 0.01). Concern with complications and sedation was positively associated with age (p < 0.001 and p < 0.001), whereas concern with colon preparation and missing work was negatively associated with age (p < 0.009 and p < 0.03). Patients with fair or poor health status were less concerned with sensitivity than patients in good to excellent health (median importance = 19.3 versus 21.4, p < 0.008). CONCLUSIONS: This pilot study suggests that patients vary in how they prioritize colorectal cancer screening test attributes; this variation is associated with test preferences, and this MDS tool is feasible to use and may help patients construct their preferences. PMID- 20309742 TI - A model of head movement contribution for gaze transitions. AB - Head posture has been associated with work-related neck symptoms and discomfort, but its relationship with visual tasks has received much less attention. Head movement amplitude is normally a fraction of the angular distance to a visual target, as gaze transition is usually achieved through the combination of both head and eye movement. In this study, the proportion of head orientation vs. target orientation, named head movement contribution ratio (HMCR), was quantified and modelled as a function of target location. Head movements were measured on subjects orienting and maintaining gaze for 2 s at randomly presented visual targets distributed along an arc placed horizontally or vertically. Bootstrap regression models showed that the horizontal HMCR was approximately 69% of target azimuth. The vertical HMCR was bilinear and corresponded to 52% and 8% and of target elevation for targets above and below the horizontal plane, respectively. The data also demonstrated that head orientation is affected by the kinematic coupling between horizontal and vertical components of head movement. STATEMENT OF RELEVANCE: Awkward head and neck posture is a risk factor for work-related musculoskeletal disorders. This study investigated the influence of visual target location on head orientation over a large range of target eccentricity, as an attempt to predict the head and neck posture required for visual target detection and identification. PMID- 20309743 TI - Evidence-based guidelines for the wise use of computers by children: physical development guidelines. AB - Computer use by children is common and there is concern over the potential impact of this exposure on child physical development. Recently principles for child specific evidence-based guidelines for wise use of computers have been published and these included one concerning the facilitation of appropriate physical development. This paper reviews the evidence and presents detailed guidelines for this principle. The guidelines include encouraging a mix of sedentary and whole body movement tasks, encouraging reasonable postures during computing tasks through workstation, chair, desk, display and input device selection and adjustment and special issues regarding notebook computer use and carriage, computing skills and responding to discomfort. The evidence limitations highlight opportunities for future research. The guidelines themselves can inform parents and teachers, equipment designers and suppliers and form the basis of content for teaching children the wise use of computers. STATEMENT OF RELEVANCE: Many children use computers and computer-use habits formed in childhood may track into adulthood. Therefore child-computer interaction needs to be carefully managed. These guidelines inform those responsible for children to assist in the wise use of computers. PMID- 20309744 TI - The performance of computer input devices in a vibration environment. AB - This study investigates the performance of a touch screen, mouse and trackball in a motion environment. A Stewart motion platform was used to generate a six-degree of-freedom motion environment. Participants were placed in an environment where vehicle vibration was simulated. Tasks were used according to Fitts' Law to obtain the movement time, error rate, index of performance and throughput of each input device. The results showed that during static conditions, the touch screen gave the best results. However, in the vibration environment, the mouse gave the best results. The trackball is the worst of the three. The error rate and end point variation tends to increase for the touch screen in the vibration environment. STATEMENT OF RELEVANCE: This study investigates the performance of a pointing device in a vibration environment. The results showed that during static conditions, the touch screen gave the best results. However, in the vibration environment, the mouse gave the best results. The track ball is the worst of the three. This research achievement can help human-computer interaction design in various dynamic environments such as in sea and land vehicles. PMID- 20309745 TI - Relationship between hand stability and the 10-Hz physiological tremor during various manual tasks. AB - To quantify an individual's ability to perform manual operations stably, the relationship between hand stability and the 10-Hz physiological tremor was investigated. A total of 35 subjects were assessed when performing force and position control tasks, which were representative of ordinary hand movements. Hand stability was analysed as two components: the fluctuation caused by voluntary control (the control error or inaccuracy when voluntarily maintaining a position or force) and the involuntary oscillatory fluctuation (physiological tremor). The control error was defined by the standard deviation of the low frequency component. The tremor was evaluated based on the power spectrum around 10 Hz. A positive correlation between the control error and the 10-Hz tremor was observed in the finger force control tasks. A correlation between finger tremor and arm tremor also was observed; subjects showing small tremors in the finger tasks also exhibited small tremors when performing the arm tasks. Taken together, the results suggested that the 10-Hz tremor can be used as a benchmark to evaluate an individual's ability to use their hands precisely. STATEMENT OF RELEVANCE: It is important to be able to quantify an individual's ability to perform precise manual operations, such as those required for microsurgery. One important aspect is instability when applying force with a finger. The relationship between hand stability and the 10-Hz physiological tremor was investigated in this study. A correlation was found between control error (or inaccuracy when voluntarily maintaining a position or force) and the 10-Hz tremor in the finger force control tasks and the results suggest that the 10-Hz tremor can be used as a measure to evaluate an individual's ability to use their hands precisely. PMID- 20309746 TI - Interactive effects from self-reported physical and psychosocial factors in the workplace on neck pain and disability in female office workers. AB - This study explored the interaction between physical and psychosocial factors in the workplace on neck pain and disability in female computer users. A self-report survey was used to collect data on physical risk factors (monitor location, duration of time spent using the keyboard and mouse) and psychosocial domains (as assessed by the Job Content Questionnaire). The neck disability index was the outcome measure. Interactions among the physical and psychosocial factors were examined in analysis of covariance. High supervisor support, decision authority and skill discretion protect against the negative impact of (1) time spent on computer-based tasks, (2) non-optimal placement of the computer monitor and (3) long duration of mouse use. Office workers with greater neck pain experience a combination of high physical and low psychosocial stressors at work. Prevention and intervention strategies that target both sets of risk factors are likely to be more successful than single intervention programmes. STATEMENT OF RELEVANCE: The results of this study demonstrate that the interaction of physical and psychosocial factors in the workplace has a stronger association with neck pain and disability than the presence of either factor alone. This finding has important implications for strategies aimed at the prevention of musculoskeletal problems in office workers. PMID- 20309747 TI - Physical characteristics related to bra fit. AB - Producing well-fitting garments has been a challenge for retailers and manufacturers since mass production began. Poorly fitted bras can cause discomfort or pain and result in lost sales for retailers. Because body contours are important factors affecting bra fit, this study analyses the relationship of physical characteristics to bra-fit problems. This study has used 3-D body scanning technology to extract upper body angles from a sample of 103 college women; these data were used to categorise physical characteristics into shoulder slope, bust prominence, back curvature and acromion placement. Relationships between these physical categories and bra-fit problems were then analysed. Results show that significant main effects and two-way interactions of the physical categories exist in the fit problems of poor bra support and bra-motion restriction. The findings are valuable in helping the apparel industry create better-fitting bras. STATEMENT OF RELEVANCE: Poorly fitted bras can cause discomfort or pain and result in lost sales for retailers. The findings regarding body-shape classification provide researchers with a statistics method to quantify physical characteristics and the findings regarding the relationship analysis between physical characteristics and bra fit offer bra companies valuable information about bra-fit perceptions attributable to women with figure variations. PMID- 20309748 TI - Occupational and environmental risk factors for falls among workers in the healthcare sector. AB - Falls are a leading cause of occupational injury for workers in healthcare, yet the risk factors of falls in this sector are understudied. Falls resulting in workers' compensation for time-loss from work from 2004-2007 for healthcare workers in British Columbia (BC) were extracted from a standardised incident reporting database. Productive hours were derived from payroll data for the denominator to produce injury rates; relative risks were derived through Poisson regression modelling. A total of 411 falls were accepted for time-loss compensation. Compared to registered nurses, facility support workers (risk ratio (95% CI) = 6.29 (4.56-8.69)) and community health workers (6.58 (3.76-11.50)) were at high risk for falls. Falls predominantly occurred outdoors, in patients' rooms and kitchens depending on occupation and sub-sector. Slippery surfaces due to icy conditions or liquid contaminants were a leading contributing factor. Falls were more frequent in the colder months (January-March). The risk of falls varies by nature of work, location and worker demographics. The findings of this research will be useful for developing evidence-based interventions. STATEMENT OF RELEVANCE: Falls are a major cause of occupational injury for healthcare workers. This study examined risk factors including occupation type, workplace design, work setting, work organisation and environmental conditions in a large healthcare worker population in BC, Canada. The findings of this research should contribute towards developing evidence-based interventions. PMID- 20309749 TI - DEXA-assessed regional body composition changes in young female military soldiers following 12-weeks of periodised training. AB - Dual-energy X-ray absorptiometry (DEXA) was used to assess whole body and regional soft tissue mass, fat mass and lean body mass compositional changes in 68 female recruits (age 20.8 +/- 1.14 years; body mass 59.5 +/- 8.79 kg; stature 159.57 +/- 5.53 cm) pre- and post 12-weeks of military basic training. A decrease in total body fat tissue mass (10.2%) and regional percent fat (10.9%) was measured with an increase in total lean body mass (8.7%). Of interest were the differences in the responses in the tissue composition of the arms (16.2% loss in fat mass with an 11.6% gain in lean mass), trunk (17.0% decrease in fat mass with a 10.4% increase in lean mass) and the legs (10.5% increase in lean mass but no change in fat mass). These findings show the importance of considering regional rather than whole body composition changes when assessing the effects of a training programme. STATEMENT OF RELEVANCE: Female soldiers experienced a change in total body fat tissue (-10.2%) and lean body mass (+8.7%) after basic training; however, no significant fat mass decrease was evident in the leg region. Regional rather than whole body composition changes need to be considered when assessing the effects of a training programme. PMID- 20309750 TI - Comparison of two tracer gas dilution methods for the determination of clothing ventilation and of vapour resistance. AB - Clothing microclimate ventilation is an important parameter in climatic stress and in contaminated environments. The two main methods for its determination (Crockford et al. (CR) 1972 and Lotens and Havenith (LH) 1988) were, after further development, compared in terms of reproducibility, validity and usability. Both methods were shown to have a good sensitivity and reproducibility (with average coefficients of variation 1.5-2.3% for the method alone and up to 7% for method and clothing/movement effects combined). They produced values very close to calibration values in forced ventilation tests (r = 0.988). Weak points for the CR method were the limits in the time constant of the measurement apparatus, causing an upper limit to the ventilation that can be reliably measured (around 800 l/min) and the method of measuring clothing microclimate volume. The original 'vacuum oversuit' (CR) method was cumbersome and prone to large errors. Alternative methods of measuring clothing microclimate volume (whole body scanner or manual circumference measurements) were shown to produce good results. For the LH method, the distribution of the tracer gas over the whole skin surface became a problem factor at very high ventilations (above 1000 l/min). As all methods use tracer gases (O(2), Ar, CO(2), SF(6)) with diffusivities smaller than that of water vapour, this potentially creates a problem in the calculation of vapour resistance from the ventilation values in the region where the emphasis of vapour transfer moves from diffusion to convection. In most real-life situations, where body and air movement are present, a correction is not however required because the error remains below 10%. STATEMENT OF RELEVANCE: Clothing ventilation indicates heat loss potential as well as risk of pollutants entering the clothing. Two main methods for its determination are compared and validated, identifying a number of issues. An in depth analysis is given of the advantages and disadvantages of the available methodologies. PMID- 20309751 TI - The role of human-at-work systems in business sustainability: perspectives based on expert and qualified production workers in a manufacturing enterprise. AB - A community of highly qualified employees is desirable for the workforce to become a competitive business advantage, improving and sustaining corporate health. Currently, the scientific literature is limited on information comparing the assessment of expert and qualified workers for the employee-work environment interface. Such information would be valuable for industrial managers to obtain and act on the different perspectives of its workers for business improvement and survivability. A primary objective of this study is to explore the perspectives of expert and qualified workers on the quality of the employee-work environment interface in a manufacturing enterprise. This investigation was performed in a production department in a small manufacturing enterprise. Two expert workers participated in the study, with each being in the company for 30 years and having performed all jobs in the production department as well as supervisory and line management responsibilities. A total of 13 qualified workers from day and night shifts were used in the study, with the great majority of workers possessing 10 or more years of on-the-job experience but not acquiring the same specialised knowledge required for operating the technological resources in the department. The work compatibility methodology was used to assess the quality of employee work environment interface for both expert and qualified workers. Both expert and qualified workers provided similar trends in terms of their compatibility assessment of experienced and acting work domains. In general, the compatibility levels for the day shift were poorer than those obtained for the night shift for acting work domains. The similarities in assessment between the expert and qualified workers were much closer for factors impacting job performance at the task and immediate surrounding levels (i.e. physical and mental task content, physical environment). There were greater differences at the macro level, that is, at the process and enterprise levels, in terms of organisational/social/technological environment. This is particularly noted for the organisational environment. The compatibility values obtained for the experienced domains mirror those obtained for acting domains. The overall workload was assessed as requiring major redesign during the day shift and needing added responsibilities for the night shift according to both expert and qualified workers. The assessment of qualified workers is comparable with that of expert workers for the job content and immediate surroundings. Differences are more observed for process- and enterprise-based factors; thereby, providing company management different perspectives in order to devise organisational strategies conducive for optimum human and corporate health and pointing to the probable interactions of the different systems impacting individual and enterprise performance. STATEMENT OF RELEVANCE: This research examines similarities and differences between qualified and expert workers in their assessment of the worker-work environment interface. The contribution to improved understanding of the complex interactions of human-at-work and enterprise systems should be beneficial to organisations in their quest to remain competitive in a global economy. PMID- 20309753 TI - Special issue of statistical genetics and genomics in clinical trials: guest editor's note. PMID- 20309754 TI - Discrete nonparametric algorithms for outlier detection with genomic data. AB - In high-throughput studies involving genetic data such as from gene expression microarrays, differential expression analysis between two or more experimental conditions has been a very common analytical task. Much of the resulting literature on multiple comparisons has paid relatively little attention to the choice of test statistic. In this article, we focus on the issue of choice of test statistic based on a special pattern of differential expression. The approach here is based on recasting multiple-comparison procedures for assessing outlying expression values. A major complication is that the resulting p values are discrete; some theoretical properties of sequential testing procedures in this context are explored. We propose the use of q value estimation procedures in this setting. Data from a gene expression profiling experiment in prostate cancer are used to illustrate the methodology. PMID- 20309755 TI - Network-based empirical Bayes methods for linear models with applications to genomic data. AB - Empirical Bayes methods are widely used in the analysis of microarray gene expression data in order to identify the differentially expressed genes or genes that are associated with other general phenotypes. Available methods often assume that genes are independent. However, genes are expected to function interactively and to form molecular modules to affect the phenotypes. In order to account for regulatory dependency among genes, we propose in this paper a network-based empirical Bayes method for analyzing genomic data in the framework of linear models, where the dependency of genes is modeled by a discrete Markov random field defined on a predefined biological network. This method provides a statistical framework for integrating the known biological network information into the analysis of genomic data. We present an iterated conditional mode algorithm for parameter estimation and for estimating the posterior probabilities using Gibbs sampling. We demonstrate the application of the proposed methods using simulations and analysis of a human brain aging microarray gene expression data set. PMID- 20309756 TI - Optimized ranking and selection methods for feature selection with application in microarray experiments. AB - In microarray experiments, the goal is often to examine many genes, and select some of them for additional investigation. Traditionally, such a selection problem has been formulated as a multiple testing problem. When the genes of interest are genes with unequal distribution of gene expression under different conditions, multiple testing methods provide an appropriate framework for addressing the selection problems. However, when the genes of interest are a set of genes with the largest difference in gene expression under different conditions, multiple testing methods do not directly address the selection goal and sometimes lead to biased conclusions. For such cases, we propose two methods based on the statistical ranking and selection framework to directly address the selection goal. The proposed methods have an inherent optimization nature in that the selection is optimized according to either a prespecified minimum correct selection ratio (r* selection) or probability of making a correct selection (P* selection). These methods are compared with the multiple testing method that controls the tail probability of the proportion of false positives. Both simulation studies and real data applications provide insight into the fundamental difference between the multiple testing methods and the proposed methods in the way of addressing different selection goals. It has been shown that the proposed methods provide a clear advantage over the multiple testing methods when the goal is to select the most significant genes (not all the significant genes). When the goal is to select all the significant genes, the proposed methods perform equally well as the current multiple testing methods. Another advantage provided by the proposed methods is their ability to detect noisy data and therefore suggest no sensible selection can be made. PMID- 20309757 TI - Evaluation of a statistical equivalence test applied to microarray data. AB - Microarray technology is commonly used to identify differentially expressed (DE) genes across conditions. A related issue that has rarely been discussed but is equally important is to identify commonly expressed genes or constantly expressed genes across different organs, tissues, or species. A common practice in the literature for such studies is to apply the differential expression analysis and conclude that a gene is unchanged if there is no statistical evidence to conclude for differential expression. However, genes that are not statistically significantly DE could be (1) truly non-DE genes or (2) truly DE genes not detected by the statistical test of differential expression due to lack of power resulted from high noise level or lack of replication. Therefore, the practice of treating non-statistically significantly DE genes as non-DE genes has the risk of including genes that are truly DE without controlling such errors. We argue that if one wants to identify genes that are truly non-DE, one needs to show statistical evidence through valid statistical tests with the appropriate type I error rate control. In this paper, we consider the identification of non-DE genes through statistical equivalence tests under the framework of multiple testing. In particular, we consider the average equivalence criterion and study the power and false discovery rate (FDR) of the standard average equivalence test, the "two one sided tests" (TOST), through extensive simulation studies based on real microarray data sets. We study the effects of various factors that can affect the power and FDR of the equivalence test including the proportion of non-DE genes. We also compare the ROC curves of the equivalence test with those of the naive method of selecting genes that are not statistically significant DE. PMID- 20309758 TI - A semiparametric Bayesian approach for estimating the gene expression distribution. AB - Gene expression microarrays are powerful tools for global comparison and estimation of gene expression. Many microarray studies have demonstrated biologically plausible results with only a few arrays, leading to a misperception that a handful of hybridized arrays can always find something meaningful. From a statistical point of view, it is important to prospectively estimate required sample sizes prior to undertaking a microarray experiment. However, all sample size calculations need to directly or indirectly estimate the unknown distribution of the effect sizes of gene expression intensities. A parametric mixture model has been developed for relating the sample size directly to the false discovery rate (FDR), the most popular multiple-comparison control criteria. In this paper, we extend the parametric mixture model and propose a robust semiparametric Dirichlet process mixture model, where the parametric distribution of gene expressions is no longer specified. This analysis is performed in a Bayesian inference framework using Markov-chain Monte Carlo steps. The usefulness of the method is illustrated by simulations and a real murine lung study. PMID- 20309759 TI - Weighted gene coexpression network analysis: state of the art. AB - Weighted gene coexpression network analysis (WGCNA) has been applied to many important studies since its introduction in 2005. WGCNA can be used as a data exploratory tool or as a gene screening method; WGCNA can also be used as a tool to generate testable hypothesis for validation in independent data sets. In this article, we review key concepts of WGCNA and some of its applications in gene expression analysis of oncology, brain function, and protein interaction data. PMID- 20309760 TI - Testing gene-treatment interactions in pharmacogenetic studies. AB - Drug-related side effects are one of the leading causes of death and illness in the developed world. Finding genes that modify drug response has the potential to significantly improve drug delivery, by identifying both individuals that can benefit from therapy and those at increased risk of harm. We present a simple approach to testing gene-by-treatment interactions in case-control pharmacogenetic studies. The approach utilizes a retrospective model that seeks to increase power through a Hardy-Weinberg equilibrium assumption among the controls, but does not assume that the event of interest is rare in the target population. We conduct extensive simulations and find that the approach shows similar or improved power, compared to standard methods, in all cases considered. We present methods for both autosomal and X-linked markers and show how the methods can be easily implemented using standard statistical software. PMID- 20309761 TI - Genotype-based risk and pharmacogenetic sampling in clinical trials. AB - A number of recent genome-wide association (GWA) studies have identified unequivocal statistical associations between inherited genetic variations, mostly single-nucleotide polymorphisms (SNPs), and common complex diseases such as diabetes, cardiovascular disease, and obesity. Genotyping individuals for these variations has the potential to help redefine how pharmacologic agents undergo clinical development. By identifying carriers of known genomic variants that contribute to susceptibility, a high-risk population can be defined, as well as individuals with potential for a better response to a drug. We evaluated the potential utility that selecting individuals for a trial on the basis of genotypes identified in contemporary GWA studies would have had on recently described clinical trials. We pursued this by constraining both the risks of a disease outcome associated with particular genotypes and overall drug responses to those actually observed in genetic association and clinical trial studies, respectively. We pursued these evaluations in the context of clinical trials investigating drugs for macular degeneration, obesity, heart disease, type II diabetes, prostate cancer, and Alzheimer's disease. We show that the increase in incidence of outcomes in trials restricted to individuals with specific genotypic profiles can result in substantial reductions in requisite sample sizes for such trials. In addition, we also derive realistic bounds for samples sizes for clinical trials investigating pharmacogenetic effects that leverage genetic variations identified in recent association studies. PMID- 20309762 TI - Haplotype-based pharmacogenetic analysis for longitudinal quantitative traits in the presence of dropout. AB - We propose a variety of methods based on the generalized estimation equations to address the issues encountered in haplotype-based pharmacogenetic analysis, including analysis of longitudinal data with outcome-dependent dropouts, and evaluation of the high-dimensional haplotype and haplotype-drug interaction effects in an overall manner. We use the inverse probability weights to handle the outcome-dependent dropouts under the missing-at-random assumption, and incorporate the weighted L(1) penalty to select important main and interaction effects with high dimensionality. The proposed methods are easy to implement, computationally efficient, and provide an optimal balance between false positives and false negatives in detecting genetic effects. PMID- 20309763 TI - Modeling the genetic etiology of pharmacokinetic-pharmacodynamic links with the ARMA process. AB - Substantial variability exists among different patients in response to drugs. The identification of genetic factors that contribute to the interpersonal differentiation has been an important task for pharmacogenetic research and drug discovery. In this article, we have derived a high-dimensional statistical model for unveiling the genetic machinery for drug response by integrating two different but biologically related processes--pharmacokinetics (PK) and pharmacodynamics (PD)--into a genetic mapping framework. Using an integrated model of PK and PD, we can identify specific DNA sequence variants and test how they relate to the differential effect of the body to the drug (PK) and the effect of the drug on the body (PD). To effectively model a two-stage hierarchic structure of the covariance matrix at the PD and PK level, we have for the first time introduced an autoregressive moving-average (ARMA) process to the mixture based likelihood function for sequence mapping. Closed-form estimates of the determinant and inverse of the ARMA-based covariance matrix are incorporated into the estimation step, which significantly increases the computational efficiency. Simulation studies have been performed to test the statistical behavior of our model. Potential applications of this model to pharmacogenetic research are discussed. PMID- 20309764 TI - A systems biology approach for identifying novel pathway regulators in eQTL mapping. AB - Expression quantitative trait loci (eQTL) mapping holds great promise in elucidating gene regulations and predicting gene networks associated with complex phenotypes. We propose a systems biology approach by incorporating prior pathway information into an eQTL mapping framework, to identify novel pathway regulators that mediate pathway expression changes. We model gene expressions in a predefined biological pathway as a multivariate response to test the joint variation changes among different genotype categories at a locus. The method is motivated and applied to a yeast data set. Significant pathway regulators and regulation hotspots are detected. The proposed method provides a powerful tool for understanding gene regulation at a pathway level. PMID- 20309765 TI - Bagging optimal ROC curve method for predictive genetic tests, with an application for rheumatoid arthritis. AB - Translation studies have been initiated to assess the combined effect of genetic loci from recently accomplished genome-wide association studies and the existing risk factors for early disease prediction. We propose a bagging optimal receiver operating characteristic (ROC) curve method to facilitate this research. Through simulation and real data application, we compared the new method with the commonly used allele counting method and logistic regression, and found that the new method yields a better performance. The new method was applied on the Wellcome Trust data set to form a predictive genetic test for rheumatoid arthritis. The formed test reached an area under the curve (AUC) value of 0.7. PMID- 20309767 TI - Summarizing and quantifying multilocus linkage disequilibrium patterns with multi order Markov chain models. AB - Studies on linkage disequilibrium (LD) are important in mapping disease genes. A novel statistical method, the multi-order Markov chain model has been recently developed to quantify the complexity level of multilocus LD patterns among single nucleotide polymorphism markers (Kim et al., 2008). In this study, mathematical relationships between two types of LD measures are derived to understand the Markov chain model parameters in terms of conventional LD measures. Statistical sample properties of the Markov chain order estimates are investigated by simulations. Two published data sets are reanalyzed to illustrate the proposed approach. PMID- 20309766 TI - Practical issues in building risk-predicting models for complex diseases. AB - Recent genome-wide association studies have identified many genetic variants affecting complex human diseases. It is of great interest to build disease risk prediction models based on these data. In this article, we first discuss statistical challenges in using genome-wide association data for risk predictions, and then review the findings from the literature on this topic. We also demonstrate the performance of different methods through both simulation studies and application to real-world data. PMID- 20309768 TI - Current progress on statistical methods for mapping quantitative trait loci from inbred line crosses. AB - Tremendous progress has been made in recent years on developing statistical methods for mapping quantitative trait loci (QTL) from crosses of inbred lines. Most of the recent research is focused on strategies for mapping multiple-QTL and associated model selection procedures and criterion. We review the progress of research in this area on one trait and multiple traits by maximum likelihood and Bayesian methods. PMID- 20309773 TI - Accuracy of the Borg CR10 scale for estimating grip forces associated with hand tool tasks. AB - The gripping of tools is required by many industrial operations, and an important aspect of exposure assessment is determining the grip force output of operators. Ratings of perceived exertion can provide an indirect measure of grip force; however, reports in the literature of the use of Borg CR10 scale ratings as a surrogate measure of grip force have been mixed. During a laboratory study with 16 participants, power grip forces were measured directly during three hand tool task simulations: (1) a screwdriver task, (2) a ratchet task, and (3) a lift and carry task, each performed at four force/load levels. Borg scale ratings reported following each trial were compared with mean, peak, and integrated grip forces for the respective trials. Pearson correlations conducted on an individual basis were greatest for the screwdriver task, r approximately 0.9. Correlations for integrated grip force were generally better than for mean or peak force. Correlations were also performed on data pooled for all participants, simulating a cross-sectional sampling approach. Correlations made with pooled data were weaker than when conducted on an individual basis, ranging from r = 0.26 for peak grip force for the lift and carry task, to r = 0.79 for the screwdriver task. When the pooled data were normalized to individual maximum voluntary grip exertions, correlation generally improved but not to the level of the "individually scaled" data. Based on these findings, a protocol is proposed that could improve the strength of correlations between direct measures of grip force and ratings of perceived exertion. Differences in strength of correlation between task simulations are discussed with respect to differences observed in force distributions about the handle for the three tasks. PMID- 20309774 TI - Further characterisation of self-defining memories in young adults: a study of a Swiss sample. AB - Several individual differences affecting four dimensions of self-defining memories (SDMs)--structure, content, affect, and autobiographical reasoning (Blagov & Singer, 2004; McLean & Fournier, 2008; Singer & Salovey, 1993)--have been observed in young adults (principally in North America). In this study we aimed to investigate the relationships between the different dimensions of SDMs, providing further evidence of the content validity of the Self-Defining Memory task. It was possible to discern two specific profiles from the three SDMs collected from each participant. Almost half the participants retrieved specific SDMs with little autobiographical reasoning and tension; the other participants retrieved an opposite profile, suggesting that there are individual differences in the cognitive and affective processes related to the construction of SDMs. The second aim of the study was to conduct across-cultural extension of research on SDMs, using a sample of Swiss young adults. The results were similar to those obtained by previous studies, suggesting a certain cultural invariability. The only difference observed concerned the number of SDMs containing meaning making. Swiss young adults attribute more explicit meanings to their memories than North American young adults, suggesting that they are more engaged in autobiographical reasoning. PMID- 20309775 TI - Comparison of illness representations dimensions and illness representation clusters in predicting outcomes in the first year following diagnosis of type 2 diabetes: results from the DESMOND trial. AB - This article explores the utility of cluster analysis of illness representations, in comparison to analysing each dimension of the individual's illness representation, to predict an individual's response to diagnosis of type 2 diabetes. Participants in a large multi-centre randomised controlled trial of a self-management education intervention for people with type 2 diabetes, completed measures of illness beliefs (coherence, timeline, impact, seriousness, personal responsibility) and depression along with HbA1c and body mass index (BMI), at baseline 4, 8 and 12 months. The results of the cluster analysis were compared with an independent qualitative study of participants' responses to diagnosis and participation in the study. The quantitative analysis of 564 participants for whom complete data were available, identified four clusters of illness representations as the most parsimonious description of the data. The mean profiles of these clusters were comparable with groups identified by the independent qualitative analysis, and predicted the trajectory of illness outcomes over the 1-year follow-up. Combining illness beliefs into discrete clusters may be more useful in understanding patterns of responding to illness than using analysis of illness beliefs dimensions independently. PMID- 20309776 TI - Lay views about medicines: the influence of the illness label for the use of generic versus brand. AB - The aim of this cross-sectional study was to investigate how different types of prescriptions using different illness labels may influence lay views about the use of generic or brand medicines. The participants were 882 Portuguese (both sexes) recruited from the general population, who completed a self-administered questionnaire. A vignette methodology was used in which different prescriptions (generic versus brand) were given for the same label (flu, hypertension, asthma and angina pectoris). The dependent variables were for each illness label: (a) the level of agreement with the prescription, (b) beliefs about the efficacy of a medicine and (c) beliefs about the relief of symptoms. There were main effects of the label and the type of prescription upon beliefs about the use of medicines. There were interactions between illness label and type of medicines. Labels which were perceived as more serious were associated with a lower belief in generic medicines. These results raise important questions concerning the need to consider illness perceptions of lay people (including perceived severity) and its relationship with perceptions of treatment for different conditions. Furthermore, these results may have implications for health-related behaviour in general, and in particular for communication between lay people and health professionals, prescribing behaviour, health costs and adherence to treatment. PMID- 20309777 TI - A volitional help sheet to increase physical activity in people with low socioeconomic status: A randomised exploratory trial. AB - Volitional help sheets use Gollwitzer's (1993) concept of implementation intentions as a vehicle to change behaviour using Prochaska and DiClemente's (1983) processes of change. The present study designed and tested a volitional help sheet to increase physical activity in a group with low socioeconomic status (low-SES). Sixty-eight people (33 women, 35 men; mean age 27) with low-SES were randomly allocated to either an experimental group or a control group. Both groups received a questionnaire and a volitional help sheet; the only difference between the experimental and control groups was that the former were given explicit instructions to link occasions on which they were tempted not to be physically active with appropriate behavioural responses (processes of change). Physical activity (Metabolic Equivalent minutes per week) was the main outcome measure; behavioural intention and self-efficacy were the secondary outcome measures. The findings revealed significant increase in physical activity in the experimental condition, relative to the control condition, F (1, 66) = 7.28, p < 0.01, eta2(10) = 0.10, but no differences for social cognitive variables. Furthermore, the participants who were most responsive to the intervention engaged in more than three times the physical activity at baseline than those who received the intervention but did not subsequently change. The findings provide further support for volitional help sheets to change health behaviour and extend them to a group with low-SES. Further work is required to refine this intervention tool. PMID- 20309778 TI - A Q-methodological study of smoking identities. AB - In contrast to the psychological literature on adolescent smoking, little research has investigated the social identities of adult smokers. This study aimed to identify shared 'smoking identities' amongst a sample of 64 British smokers from different socio-economic groups using Q-methodology. Participants were asked to sort 70 items concerning smoking and smokers according to their agreement/disagreement with them. The 64 Q-sorts were then subjected to a by person factor analysis yielding six factors, with the first four interpretable factors being presented here. Each factor is understood to represent a distinct 'identity position'. The first two, the 'addicted' smoker, and the 'in control' smoker, oriented around a biomedical model of smoking as an addictive health risk. The final two, the 'no big deal' smoker and the 'proud' smoker reflected alternative understandings and values. The identity positions also differed in the extent to which smoking was considered a core part of self-identity. Unpacking the 'smoking identities' of current smokers offers the opportunity to devise targeted health promotion. PMID- 20309779 TI - The relationship between religious/spiritual factors and perceived growth following a diagnosis of breast cancer. AB - This study investigates the role of religious salience, God image and religious coping in relation to perceived growth following a diagnosis of breast cancer. Eighty-seven breast cancer patients were followed from pre-diagnosis up to 24 months post-surgery. The findings of this study provided limited support for the role of positive aspects of spirituality in relation to perceived growth. Religious involvement at pre-diagnosis was predictive of less growth at 24 months post-surgery while a positive image of God had no association with growth. While some forms of positive religious coping demonstrated positive associations, others evidenced no relationship or negative relationships with growth. Negative aspects of spirituality were more consistently related to growth with the nature of the association again depending on the type of negative spirituality being assessed. For example, passive deferral coping was related to less growth while spiritual discontent coping was related to greater growth across time. Such findings underscore the need to attend to negative aspects of spirituality from early on in the process of cancer adjustment as such expressions may have implications for women's ability to develop and maintain a positive perspective in their coping over the long-term. PMID- 20309780 TI - Who cares, who bears, who benefits? Female spouses vicariously carry the burden after cancer diagnosis. AB - BACKGROUND AND AIM: Among couples coping with cancer diagnosis, the effects of gender, role (patient vs. spouse) and patient relationship status (single vs. partnered) on quality of life (QoL) have been investigated with inconsistent results. The present study examined the impact of gender, role and relationship status on male and female patients, their spouses and non-partnered patients. METHOD: A representative sample of 218 patients with a new primary cancer diagnosis (any type and stage) and their spouses (n = 137), were assessed within 8 weeks of diagnosis. Measures assessed multiple QoL dimensions including health related and dyadic QoL as well as symptoms of distress: (anxiety, depression, intrusion, avoidance and hyperarousal). RESULTS: Multivariate analyses of covariance revealed lower QoL for women versus men, and for spouses versus patients on a number of measures (health-related QoL, satisfaction with dyadic coping, anxiety and intrusions). CONCLUSIONS: Female spouses of cancer patients are at high risk of deteriorated QoL immediately after diagnosis, and require special attention to their psychosocial care needs. PMID- 20309781 TI - Children's sense of coherence and trait emotional intelligence: a longitudinal study exploring the development of somatic complaints. AB - The objective of this study was to investigate the prospective relationships between sense of coherence, trait emotional intelligence and children's somatic complaints. The study included four waves of data collection with six months in between each wave. Participants were 324 girls and 393 boys (mean age = 10 years and 3 months, SD = 8.5 months) at the first time of data collection. The children filled out self-report questionnaires concerning their somatic complaints, sense of coherence and trait emotional intelligence. Multilevel model analyses were carried out that included cross-sectional and longitudinal effects of sense of coherence and trait emotional intelligence on children's somatic complaints. The results showed that higher levels of trait emotional intelligence and a stronger sense of coherence were associated with fewer somatic complaints in children. These relationships seemed to be bidirectional. PMID- 20309782 TI - Predictors of perceived social support in long-term survivors of cardiac transplant: the role of psychological distress, quality of life, demographic characteristics and clinical course. AB - AIM: To examine associations between perceived social support, quality of life, psychopathological, demographic and clinical variables in long-term heart transplant survivors. METHODS: Sixty six patients transplanted from 10.2 +/- 3.3 years completed the Interpersonal Support Evaluation List, Symptom Questionnaire and World Health Organization Quality of Life-BREF. Parameters of post-transplant medical course were retrieved. Spearman rank order correlation, Mann-Whitney U test, Kruskal-Wallis test and multiple regression analyses were performed. RESULTS: At multiple regression analyses SQ depression significantly predicted Interpersonal Support Evaluation List (ISEL) total and appraisal scores (p = 0.005 and p = 0.047), indicating better satisfaction for support in patients with less depressive symptoms. Low levels of depression and being married or living as married were significantly associated with better ISEL belonging (p = 0.03 and p = 0.008) and self-esteem (p < 0.001 and p = 0.038). Skin cancer significantly correlated with better tangible (p = 0.02) and total (p = 0.05) support. Social quality of life was positively associated with ISEL total (p < 0.01), appraisal (p < 0.05), belonging (p < 0.01) and tangible (p < 0.05) scores; yet, it significantly predicted none of the them. CONCLUSIONS: Depressive symptoms may worsen patients' satisfaction for their interpersonal support. Marital status seems to foster sense of belonging and self-esteem. The paucity of significant associations between ISEL and clinical parameters may reflect the caregivers' continuous provision of support regardless of clinical status. PMID- 20309783 TI - [New insights in the differential diagnosis of bladder pain syndrome]. AB - The diagnosis of bladder pain syndrome/interstitial cystitis (BPS/IC) is challenging, since pathogenetic mechanisms and the definition of clinical relevant parameters are still under lively discussion. The criteria recently proposed by the European Society for the Study of Interstitial Cystitis (ESSIC) define a collective of patients based on the cardinal symptom of bladder pain which is heterogeneous, and therefore cannot receive standardised consistent therapy. Thus an extended diagnosis based on molecular markers seems to be indicated to render individual pharmacotherapy possible, and to contribute to elucidation of BPS/IC pathogenesis. For this purpose we feel the vital need for taking a bladder biopsy. The diagnosis of BPS/IC should rely on 3 "columns": (1) clinical diagnostics; (2) histopathology; (3) molecular diagnostics/protein expression. Since a significant contribution of the 3 functional units of the bladder to the pathophysiology is most evident, the examinations should ideally include urothelium, lamina propria, and detrusor musculature. Generation of receptor profiles of the detrusor muscle represents a first attempt to define a diagnostic tool for the individualisation of BPS/IC pharmacotherapy. Other factors, e.g., beta-hCG expression in the urothelium, need further evaluation. Extended BPS/IC diagnostics could be realistically integrated into routine patient care within a clinic/laboratory network. PMID- 20309784 TI - [Preventive prepubic urethrectomy]. PMID- 20309785 TI - Chronic flexibility improvement after 12 week of stretching program utilizing the ACSM recommendations: hamstring flexibility. AB - The ACSM flexibility training recommendations emphasize proper stretching of muscles supporting the major joints, but there is a little evidence to support this recommendation in terms of effectiveness, and which stretching parameters (technique and single stretch duration) are more adequate. A randomized controlled clinical trial design was use to investigate whether the ACSM flexibility training recommendation parameters improve hip flexion range of motion. A total of 173 subjects, 122 men (21.3+/-2.5 years; 176.33+/-8.35 cm; 74.42+/-10.80 kg) and 51 women (20.7+/-1.6 years; 163.43+/-6.57 cm; 60.12+/-7.88 kg), classified as recreationally active young adult university students were randomly assigned to 1 of 7 groups: 1 control group (no stretching) or 1 of 6 stretching groups. All stretching groups performed 12 weeks of flexibility training with a consistent stretch daily dose (180 s) and frequency (3 days per week) parameters and different stretch technique (passive or active) and single stretch duration (15, 30, or 45 s). Hip flexion passive range of motion (PROM) was determined through the bilateral straight-leg raise test before, during (at 4 and 8 weeks), and after the program (12 weeks). All stretching groups performed hip flexion PROM after flexibility training. A significant improvement was identified in mean PROM for each stretching group, but no significant differences were found between stretch technique and single stretch duration (p>0.05). The control group's mean PROM decreased (Delta PROM: -0.08 degrees, 95% confidence interval [CI]=-2.3 to 5.3), whereas all stretching groups increased PROM (Delta PROM: 15.14 degrees, 95% CI=10.19 to 23.56) in hip flexion after 12 weeks of stretching (p<0.05). The present study suggests that the current ACSM flexibility training recommendations are effective for improving hip flexion ROM in recreationally active young adults. PMID- 20309786 TI - Asymmetry of force fluctuation in knee extension. AB - The purpose of this study was to investigate the asymmetry of force fluctuation and mechanomyogram (MMG) signal during low intensity isometric knee extension. Twelve healthy males (21+/-1 years) performed unilateral force matching tasks; sustained isometric knee extension for 15 s at levels corresponding to 10% and 20% maximal voluntary contraction (MVC) with the visual feedback of force. During the force matching tasks, MMG was detected by an accelerometer arrangement placed on the vastus lateralis. Power spectrum density of the MMG was obtained by the fast Fourier transformation method, and mean power frequency (MPF) was calculated. Force fluctuation, amplitude of MMG and MPF of MMG were significantly increased in 20% MVC task compared to the 10% MVC task in both limbs. Significant differences between stronger MVC limb and weaker MVC limb were not observed in force fluctuation, amplitude of MMG and MPF of MMG during 10% and 20% MVC tasks. These results suggest that the asymmetry of force steadiness during low intensity isometric knee extension was not observed because there was no difference regarding mechanical characteristics in active muscle between stronger and weaker limbs. PMID- 20309787 TI - [Cannabis use disorders]. PMID- 20309788 TI - Central hypothyroidism due to malnutrition in a 6-year old girl. PMID- 20309789 TI - Continuous venovenous hemofiltration rapidly lowers toxic metabolites in a patient with MSUD and imminent cerebral herniation. AB - Maple syrup urine disease (MSUD) is an inborn error of amino acid metabolism. During catabolic stress encephalopathy and brain swelling that can culminate in brain herniation may occur. Beyond the neonatal period, these metabolic decompensations normally can be treated with a conservative dietary emergency regimen. Nevertheless in exceptionally severe cases also older patients may require extracorporeal interventions. We present the case of a 12-year-old patient with cerebral edema and imminent cerebral herniation. Continuous venovenous hemofiltration (CVVH) caused a prompt decrease of the toxic metabolite levels as well as an improvement of the patient's condition. PMID- 20309790 TI - [Lysosomal storage diseases - update and new therapeutic options]. AB - Lysosomal storage diseases represent a group of about 50 genetic disorders. The deficiencies of lysosomal and non-lysosomal proteins cause an accumulation of compounds which are normally degraded within the lysosome. There are currently no therapeutic options to cure patients suffering from a lysosomal storage disease. Due to their progressive nature there is considerable morbidity and mortality. Thus, an early treatment to maintain major systemic functions is of utmost importance. While so far only symptomatic therapies are in use, the newly available enzyme replacement therapies offer a real causal approach for selected storage diseases. Many of these disorders are characterised by pathognomonic eye findings. Therefore, the ophthalmological examination provides the opportunity for an early and non-invasive diagnosis and a chance to initiate early treatment. This review is intended to give a survey of the most common lysosomal storage diseases, particularly with regard to ophthalmological changes as well as illustrate new therapeutic options. PMID- 20309791 TI - [Idiopathic non-specific orbital inflammation: anatomic classification and treatment options]. AB - BACKGROUND: The aim of this study was to identify the clinical presentation of idiopathic non-specific orbital inflammations (NSI) in relation to the anatomic pattern of involvement in the orbit and to evaluate the treatment options. PATIENTS AND METHODS: 35 cases of patients with NSI were retrospectively reviewed. In all cases the diagnosis was confirmed by biopsy of the lesion. 10 patients exhibited a severe amount of fibrosis in biopsy specimens in terms of an idiopathic sclerosing non-specific orbital inflammation (SNSI). The patients were treated with corticosteroids, radiotherapy or surgery (en-block excision or orbital decompression/debulking). Follow-up data were available for 27 / 35 patients for a period of 2 to 24 months after initial diagnosis. RESULTS: The anatomic pattern of involvement was anterior in 7 / 35, intraconal in 5 / 35, diffuse in 1 / 35, apical in 2 / 35, and lacrimal in 20 / 35 patients. 16 patients with NSI were initially treated with systemic corticosteroids. 12 / 16 patients had a complete regression of symptoms, 1 / 16 patients had partial regression and 3 / 16 patients had no improvement. 4 patients with SNSI were initially treated with systemic corticosteroids. 3 / 4 patients with SNSI had no improvement under steroid therapy. 1 patient with SNSI received no treatment and no progression was observed on follow-up. 7 patients (3 with NSI and 4 with SNSI) were treated surgically. In 5 / 7 (2 with NSI and 3 with SNSI) surgical therapy was the initial treatment due to well-circumscribed lesions in orbital imaging, whereas in 2 / 7 orbital decompression with debulking was performed after failure of systemic corticosteroids. 5 / 7 patients had a complete resolution of symptoms, whereas 2 / 7 had a partial resolution with persistent postoperative diplopia. 3 patients were treated with radiotherapy. In 2 / 3 previous steroid therapy was unsuccessful in controlling the disease. 2 / 3 of these patients had complete regression and 1 / 3 partial regression of symptoms. CONCLUSIONS: Classification of NSI according to their anatomic pattern of involvement provides a useful framework for the clinical evaluation of these patients. Systemic steroids should be the first-line therapy in cases with NSI. However, if severe fibrosis in terms of SNSI is present, corticosteroid therapy is very likely to fail, so that surgical therapy should be considered early, especially in cases of relatively well-circumscribed lesions. PMID- 20309792 TI - Xanthohumol and related prenylated flavonoids inhibit inflammatory cytokine production in LPS-activated THP-1 monocytes: structure-activity relationships and in silico binding to myeloid differentiation protein-2 (MD-2). AB - Xanthohumol (XN) is a prenylated chalcone-type flavonoid found in hops and beer. Our objective of this study was to determine the anti-inflammatory activities of XN, isoxanthohumol (IX), and 15 related prenylated chalcones and flavanones, as well as their structure-activity relationships. The anti-inflammatory activities of the flavonoids were measured by their ability to inhibit lipopolysaccharide (LPS)-induced cytokine production in human monocytic THP-1 cells. The position, number, and length of the prenyl groups had a marked influence on the inhibitory activity of the prenylfavonoids towards MCP-1 and IL-6 production. The alpha,beta unsaturated carbonyl moiety present in chalcones such as XN was not an absolute requirement for inhibitory activity, as the saturated XN derivative, tetrahydroxanthohumol (TX), showed inhibitory activity comparable to XN. With the aim to determine the mechanism of the observed anti-inflammatory effects, cellular protein levels of Toll-like receptor 4 (TLR4) were measured by Western blot 24 h following coexposure of THP-1 cells to LPS and either XN, TX, or IX. Only XN reduced the cellular TLR4 protein content. Therefore, an additional hypothesis was developed for an anti-inflammatory mechanism that involves the TLR4 coreceptor myeloid differentiation protein-2 (MD-2), which provides the actual binding site for LPS. Molecular docking studies showed that the complementarity of prenylated flavonoids with the hydrophobic MD-2 pocket (indicating goodness of fit) directly predicted their relative ability to inhibit MCP-1 and IL-6 production. In conclusion, prenylated flavonoids may suppress LPS induced TLR4 activation at least partly by interfering with LPS binding to the TLR4 coreceptor MD-2, and XN (but not other prenylflavonoids) exerts an additional anti-inflammatory effect by downregulating the cellular TLR4 protein content. PMID- 20309793 TI - Phytochemical characterization of Rhododendron ferrugineum and in vitro assessment of an aqueous extract on cell toxicity. AB - Within a systematic phytochemical investigation of the leaves of RHODODENDRON FERRUGINEUM L. (Ericaceae), the volatile oil was isolated (0.7 %) and its constituents were characterized. Eleven flavonoids were isolated and characterized, with quercetin 3- O-[6''- O-(2-methyl-1-oxobutyl)]-beta- D glucopyranoside and 2 R,3 R-dihydromyricetin 3- O- beta- L-arabinopyranoside as new natural products. Beside monomeric flavan-3-ols (catechin, epicatechin, gallocatechin, epigallocatechin) from the tannin fraction (about 3.5 % calculated as pyrogallol), the dimeric procyanidins B1 to B7 were identified, as well as the trimeric compounds procyanidin C1, epicatechin-(4 beta -> 8)-epicatechin-(4 beta > 8)-catechin and the trimeric A type-linked cinnamtannin B1. Additionally, phloroacetophenon 4- O- beta- D-glucopyranoside and chlorogenic acid were isolated. Water-soluble carbohydrates comprised about 13.5 % of the dried leaves, including fructans (3 %), polysaccharides (1 %) (mainly type II arabinogalactans), glucose, fructose, sucrose, stachyose and raffinose. The IN VITRO effects on cellular vitality (MTT test), proliferation (BrdU incorporation) and necrosis (LDH release) of an aqueous extract were investigated. The extract did not exert any toxic effects, while the vitality and the proliferation rates of epithelial HaCaT keratinocytes were significantly increased at 100 ug/mL, indicating that the aqueous extract does not have negative effects against cellular activity. PMID- 20309794 TI - Arisanschinins A-E, lignans from Schisandra arisanensis hay. AB - Four new oxygenated dibenzocyclooctadiene lignans, arisanschinins A-D ( 1- 4), and a new 1,4-bis(phenyl)-2,3-dimethylbutane lignan, arisanschinin E ( 5), together with 15 known compounds, were isolated from the EtOAc-soluble fraction of the aerial parts of SCHISANDRA ARISANENSIS Hay. The structures of 1- 5 were elucidated on the basis of extensive spectroscopic analyses, including 2D NMR (HMQC, HMBC, and NOESY) experiments. The configurations of the biphenyl and octadiene moieties were deduced from circular dichroism (CD) and NOESY spectra, respectively. Compound 1 showed significant inhibition of alpha-glucosidase IN VITRO. The radical-scavenging activities of these compounds were evaluated using DPPH. PMID- 20309795 TI - Bisnortriterpenoids possessing an 18-Nor-schiartane skeleton from Schisandra propinqua var. propinqua. AB - Six C (28) triterpenoids with an 18-nor-schiartane framework were isolated from the aerial parts of SCHISANDRA PROPINQUA var. PROPINQUA. The new compounds, propindilactones P-S ( 1- 4), were structurally characterized by extensive spectroscopic methods. New compounds 2 and 3, together with known wuweizidilactones B and H ( 5- 6), were evaluated for their anti-HBV activity. PMID- 20309796 TI - The antinociceptive effect of a benzopyran (HP1) isolated from Hypericum polyanthemum in mice hot-plate test is blocked by naloxone. AB - Several species of the genus Hypericum (Guttiferae) have been used for analgesic purposes all over the world and some of them have demonstrated to possess this effect in rodents. This study describes the antinociceptive effect of the cyclohexane extract from aerial parts of H. polyanthemum (POL) as well as of benzopyrans, 6-isobutyryl-5,7-dimethoxy-2,2-dimethyl-benzopyran (HP1), 7-hydroxy 6-isobutyryl-5-methoxy-2,2-dimethyl-benzopyran (HP2), and 5-hydroxy-6-isobutyryl 7-methoxy-2,2-dimethyl-benzopyran (HP3), which are the main components of POL. The antinociceptive effect was evaluated through hot-plate and writhing tests in mice, and the opioid system involvement was assessed by using naloxone (2.5 mg/kg, s.c.) antagonism. In the hot-plate test, POL (45, 90, 180 mg/kg, p.o) showed a dose-dependent effect, and out of the benzopyrans only HP1 (30, 60, 90 mg/kg, i.p.) was active. Its effect was also dose-dependent, with the maximum reached at 60 mg/kg. HP1 60 mg/kg (p.o.) also inhibited acetic acid-induced writhing in 58%. The pretreatment with naloxone abolished the antinociceptive effect of HP1 60 mg/kg (i.p) in the hot plate. Furthermore, the H. polyanthemum cyclohexane extract and HP1 did not affect the mice performance in the rota-rod apparatus suggesting that at antinociceptive doses they do not present gross neurotoxicity nor induce motor impairment. From these data it is reasonable to assume that the benzopyran HP1 accounts for the H. polyanthemum cyclohexane extract antinociceptive effect, and this effect is, at least in part, mediated by an opioid-like mechanism. PMID- 20309797 TI - Development of a coculture system to evaluate the bioactivity of plant extracts on pancreatic beta-cells. AB - Natural plant extracts are candidates for the development of new functional foods. Most of them are usually complex mixtures of molecules of uncertain bioavailability that are often partially metabolized before they finally reach the target cells IN VIVO. IN VITRO studies of the bioactivity of these extracts suggest that their direct application to some cell cultures might be a long way from becoming a reality. To overcome this limitation, we seeded Caco-2 cells onto culture inserts and after 21 days, cocultured these with INS-1E on the base of the well. After 24 hours of coculture, TEER (transepithelium electrical resistance) measurements indicated no changes in the permeability of the Caco-2 barrier. We also found no changes in either the ability of Caco-2 cells to metabolize the flavan-3-ol component of a grape-seed procyanidin-rich extract, or in the flavanols' ability to pass through the barrier. However, the expression of the Caco-2 SGLT-1 gene increased due to the coculture. GSIS (glucose stimulated insulin secretion) was maintained in the INS-1E cells with higher levels of insulin secretion despite the fact that the insulin gene expression was unmodified by the cocultivation. Furthermore, we found that in some of the assays requiring several medium changes there was a tendency to lose beta-cells. Neutral red assay showed that seeded cells should only be cocultured for a short time to obtain a higher consistency. In conclusion, four hours coculture with Caco-2 cells and INS-1E is a suitable method for checking the bioactivity of natural plant extracts of unknown bioavailability on beta-cells. PMID- 20309798 TI - Fo shou san, an ancient herbal decoction prepared from rhizoma chuanxiong and radix angelicae sinensis, stimulates the production of hemoglobin and erythropoietin in cultured cells. AB - Fo Shou San (FSS) is an ancient herbal decoction comprised of Rhizoma Chuanxiong (RC; Chuanxiong) and Radix Angelicae Sinensis (RAS; Danggui) in a ratio of 2 : 3. It is mainly prescribed for patients having a blood deficiency. This combination is considered the most popular herb pair among Chinese medicines; however, the rationale of having these two chemically similar herbs within the decoction has historically not been made clear. Here, we attempted to reveal the chemical and biological properties of this decoction as a means to deduce its mechanism of action. The effects of FSS were determined in different cell culture models. With respect to stimulation of blood circulation, FSS inhibited ADP-mediated platelet aggregation in a dose-dependent manner. In order to reveal the hematopoietic effect of this decoction, FSS was applied onto cultured K562 human leukemia cells and Hep3B human hepatocellular carcinoma cells. Application of FSS in cultured K562 cells inhibited cell proliferation and subsequently induced the production of hemoglobin. Additionally, the mRNA expression of erythropoietin (EPO) was induced in a dose-dependent manner when FSS was applied to Hep3B cells. The current results reveal the effects of FSS in different cell models, paving a direction for mechanistic studies. PMID- 20309799 TI - Two prenylated and C-methylated flavonoids from Tripterygium wilfordii. AB - Two unusual prenylated and C-methylated flavanones, (+/-)-5,4'-dihydroxy-2' methoxy-6',6''- dimethypyrano-(2'',3'':7,8)-6-methyflavanone ( 1) and (2 S) 5,7,4'-trihydroxy-2'-methoxy-8,5'- di(3-methyl-2-butenyl)-6-methyflavanone ( 2), and 10 known compounds were isolated from the stems and roots of TRIPTERYGIUM WILFORDII. Their structures were elucidated based on spectroscopic analyses including 1- and 2-D NMR, HR-ESI-MS, CD, and x-ray crystallography. The anti inflammatory, antiproliferative, and antibacterial activities of compounds 1 and 2 were investigated. Compound 2 had an inhibitory effect on lipopolysaccharides (LPS)-triggered RAW cell nitric oxide (NO) production, with an IC (50) value of 15.0 +/- 0.7 uM. Both compounds showed moderate antiproliferative activity against the tumor cell lines HT-29 and ZR-75-1. PMID- 20309800 TI - [Compulsive hoarding - a literature review]. AB - OBJECTIVE: To provide an overview of empirical findings with regard to compulsive hoarding. METHODS: A systematic literature search of medical and psychological journals was conducted using PubMed. Relevant publications from the reference lists and recent books were also identified and included. RESULTS: The article reviews the phenomenology, diagnosis, etiology, neurobiology, prevalence, conceptualization, and treatment of compulsive hoarding. Compulsive hoarding is characterized by excessive acquisition, difficulty discarding possessions, clutter that precludes activities for which living spaces where designed and it causes significant distress, family and socioeconomic burden. Neuropsychological studies and neuroimaging indicate dysfunction of the anterior cingulated cortex and other ventral and medial prefrontal cortical areas. CONCLUSIONS: Further research is required to resolve the controversy as to whether compulsive hoarding is characteristic of a subtype of OCD or an unique syndrome and to develop disorder specific treatments. PMID- 20309801 TI - Outcome of craniocerebral gunshot injuries in the civilian population. Prognostic factors and treatment options. AB - AIM: Gunshot wounds to the head are rare in Europe. They may be inflicted by low velocity handguns, captive bolt guns and tear gas cartridges and mostly result from suicide attempts. The experience of neurosurgeons with this kind of traumatic injury is decreasing; the aim of this study was therefore to analyse prognostic factors which help to decide whether or not to operate and to discuss treatment options. METHODS: Thirty patients with gunshot head injuries treated in our hospital from 1993 to 2008 were retrospectively evaluated. Glasgow Coma Scale (GCS) score, pupil reactivity, lesion localisation, number of bone fragments, intracranial pressure (ICP), midline shift, hypotension, and dural penetration were analysed for their prognostic value. Surgically and non-surgically treated patients were evaluated separately. Complications were registered. RESULTS: A low GCS of 3-8, fixed pupils, >2 bone fragments, bilobar or posterior fossa/brainstem lesions and ICP >45 mmHg were indicators of a poor prognosis. CONCLUSION: Patients with a GCS of 3-8 and two non-reactive pupils should not be operated. If one or both of the pupils are reactive, surgery should be performed irrespective of the GCS score, except in patients with translobar/transventricular wounds. Even if there are no clear contraindications to surgery, the outcome is expected to be poor in patients with a low GCS score, midline shift >10 mm, >2 bone fragments in the brain, and a bilobar, posterior fossa/brainstem or ventricular lesion and ICP >45 mmHg. When surgery is performed the wound and the missile or bone track should be debrided meticulously, the wound and dura should be closed in a watertight fashion and antibiotic prophylaxis as well as tetanus serum should be given. PMID- 20309802 TI - Versatility of chimeric flap based on thoracodorsal vessels incorporating vascularized scapular bone and latissimus dorsi myocutaneous flap in reconstructing lower-extremity bone defects due to osteomyelitis. AB - To treat lower-extremity osteomyelitis secondary to trauma, bone and soft tissue can be grafted at the same time using microsurgical techniques. We investigate the use of chimeric flaps based on thoracodorsal vessels incorporating vascularized scapular bone and latissimus dorsi myocutaneous flap to reconstruct bone and soft-tissue defects of the lower leg due to osteomyelitis. Ten patients with lower-extremity bone and soft-tissue defects due to osteomyelitis were treated. Vascularized scapular bones were raised on the angular branch of the thoracodorsal artery. Latissimus dorsi myocutaneous flaps were elevated simultaneously to reconstruct the soft tissue defects. All patients tolerated the procedure well. One patient developed an early venous thrombosis, which was successfully treated by thrombectomy. Mean follow-up time was 7 years and 8 months. Bone union without refracture was observed in all patients. The mean time required for bone union after surgery was 13.5 weeks. Donor-site morbidity was minimal. Chimeric flaps based on thoracodorsal vessels incorporating vascularized scapular bone and latissimus dorsi myocutaneous are safe and effective in the repair of lower-extremity bone and soft-tissue defects caused by osteomyelitis. PMID- 20309803 TI - A novel technique for lower extremity limb salvage: the vastus lateralis muscle flap with concurrent use of the vacuum-assisted closure device. AB - Free tissue transfer is an essential component of lower extremity limb reconstruction and has dramatically improved salvage attempts. In this report, we examine the use of the underutilized free vastus lateralis muscle flap and describe our treatment protocol that involves a novel application for the vacuum assisted closure device in an effort to reduce edema and congestion in lower extremity limb salvage. Thirteen patients underwent reconstruction with 14 vastus lateralis flaps with closure occurring on average 35.2 days after injury and an average case duration of 4:34 days. We report one flap failure, one superficial abscess, and one donor site hematoma. All patients were ambulatory at 6 months. Our early experience using this underutilized flap and novel protocol demonstrate successful lower extremity reconstruction with few complications, and good function and contour. Given its advantages, this versatile flap should be included as an option in lower extremity limb salvage operations. PMID- 20309804 TI - [Concordance of the Gleason score in prostate multibiopsy and definitive histology]. AB - BACKGROUND: Due to an insufficient mean agreement between the Gleason score (GS) revealed from multibiopsy and definitive histology after radical prostatectomy (RP) of merely about 45 %, a modification of the GS including an elimination of GS 2-4 was -accomplished in 2005. The aim of the present study was to evaluate the concordance of GS and WHO grading in biopsy and definitive histology and to determine parameters influencing the diagnostic accuracy of the biopsy and the prognosis. MATERIALS AND METHODS: Within a 10-year-period before modification of the GS, radical prostatectomy was performed in 856 patients (study group, SG; mean age 64.2 years). The grade of agreement between GS and WHO grading in biopsy and definitive histology was calculated by kappa statistics (kappa) (for the complete and single time -periods). Furthermore, we assessed the univariable and multivariable influence of different preoperatively available parameters on disease-free survival (DFS). The mean follow-up period was 39 months (range: 10 139 months). RESULTS: Undergrading of GS and WHO grading decreased continuously within the three time -periods in favour of a higher agreement regarding the histological results revealed from biopsy and definitive histology. However, we found only a poor to moderate agreement in the complete time period (kappa values of 0.354 for GS and 0.404 for WHO grading) that - with regard to both parameters was improved by an increased number of biopsy cores taken. PSA value, clinical tumour stage, number of positive cores (dichotomised at 34 %), annual RP case load (dichotomised at 75), and GS revealed an independent significant influence on DFS. Patients with GS 2-4 in the biopsy exhibited an upgrade to GS > or = 7 in only 5.7 %, and -showed, -independent of the definitive histology, a significantly better prognosis in comparison with patients presenting with a higher GS. CONCLUSIONS: The results of the present study again suggest the independent prognostic impact of the GS revealed from biopsy. However, the concordance with the GS in the definitive histology remains deficient and is improvable by taking a higher number of biopsy cores. Although the elimination of GS 2-4 might be comprehensible for the pathologist's purpose, it results in a considerable loss of pretherapeutic prognostic information. PMID- 20309805 TI - [Solitary fibrous tumor of the seminal vesicle]. AB - A 56-year-old man presented to our hospital with a pelvic mass. The tumor was diagnosed to occur from right seminal vesicle and to be a benign solitary fibrous tumor by transrectal tumor biopsy. The tumor enlarged during follow up, and he under-went resection of the tumor. PMID- 20309806 TI - [Hiatoplasty reinforcement by means of a lightweight titanized polypropylene mesh fixed with fibrin glue]. AB - INTRODUCTION: Suture-based hiatoplasty is associated with a high recurrence rate. Using meshes of different shapes and materials to reinforce these sutures reduces the risk of recurrences. On the other hand morbidity attributable to the suture and tack fixation of these meshes has been observed during the development phase of these techniques. Moreover, there are some experimental and clinical data about mesh migration into the oesophageus. For this reason we analysed the outcome of our patients who underwent a mesh-reinforced hiatoplasty with a lightweight titanised polypropylene mesh fixed by fibrin glue. PATIENTS AND METHODS: All the patients who under-went a mesh-reinforcement between 3 / 2006 and 12 / 2007 were collected retrospectively. The hiatoplasty was reinforced by means of a lightweight titanised polypropylene mesh that had been designed especially for that purpose (TiSure(r), GfE). Mesh fixation was performed with 2 mL of fibrin glue (Tissucol(r), Baxter). Postoperative data were elucidated for all patients via their general practitioner or by interviewing the patients by telephone using a dedicated questionnaire. RESULTS: 26 patients with a median age of 58 years and a median BMI of 27.5 kg / m2 underwent laparoscopic mesh reinforced hiatoplasty. There were 15 axial and 11 paraoesophageal hernias, in 5 cases with upside-down stomach and in 4 cases recurrent hernias. 15 patients underwent an additional dorsal 270 degrees -fundoplication, the remaining 11 patients had a fundophrenicopexy, with conversion taking place in 2 cases. The median follow-up was 34.3 months. 3 patients suffered from dysphagia, 1 of them had to be re-operated and has been free of symptoms since then. 2 patients suffered from mild gastrooesophageal reflux which was treated conservatively. So far no mesh migration and no recurrences have been seen. CONCLUSIONS: Despite the short observation time, this study indicates the patients are not exposed to any danger by the lightweight titanised polypropylene mesh. Moreover, the mesh appears to enhance hiatorrhaphy safety even in the presence of extensive hiatal hernias as well as in the case of an upside-down stomach. PMID- 20309807 TI - [Erosive bleeding of the cystic artery into a cholecysto-colic fistula as a rare cause of acute gastrointestinal bleeding]. AB - Acute gastrointestinal bleeding is one of the most frequent medical emergencies. The most common causes are inflammations, ulcers, neoplasms and angiodysplasias. They can usually be diagnosed and treated via endoscopy, but less frequent causes, which require increased diagnostic and therapeutic efforts, must also be considered. We present the case of a 53-year-old patient with gastrointestinal bleeding. He was diagnosed with transverse colon bleeding in another hospital. A bleeding diverticulum was assumed. Following admission to our hospital, a bleeding through the ampulla of Vater was discovered via gastroscopy. The CT scan showed arterial bleeding into the gallbladder. We immediately performed a laparotomy and found a cholecysto-colic fistula as the cause of the bleeding into the transverse colon. PMID- 20309808 TI - [Mesh-wrapping of a traumatised liver with active bleeding: a subsequent complication--obstruction of the inferior vena cava]. AB - In multiply traumatised patients injuries of the -liver are frequently seen. Depending on location and extent of the trauma, different techniques can be applied. In the presented case of a central liver trauma in a 21-year-old man with active bleeding, mesh-wrapping of both liver lobes was applied to achieve control of the bleeding. Postoperatively the patient developed constant hypertension, oliguria and severe anasarka of the lower half of the body caused by a near total obstruction of the inferior vena cava. After removal of the wrappings, all symptoms slowly disappeared. This case and the findings in similar cases in the literature suggest that there is an indication for wrapping a traumatised liver rather with diffuse and peripheral bleeding than with a central liver trauma. PMID- 20309809 TI - Combination therapy in the treatment of schizophrenia. AB - BACKGROUND: Although the international guidelines for the treatment of schizophrenia recommend antipsychotic monotherapy as the treatment of choice, many schizophrenia patients receive two or more antipsychotics in clinical practice, while co-treatment with antidepressants, mood stabilizers and benzodiazepines is also common. AIM: The aim of the present review is to summarize the results of the randomized controlled trials of combination therapy versus monotherapy in schizophrenia and to discuss possible implications of these results. DISCUSSION: Altogether, recommendations are based upon theoretical assumptions rather than upon evidence-based knowledge regarding the combination of different antipsychotics or antipsychotics with other psychotropic agents in schizophrenia treatment, since the available studies reveal conflicting results. The augmentation with antidepressants for the treatment of persisting negative symptoms and with mood stabilizers in patients with additional affective symptoms seems to be a successful strategy. CONCLUSIONS: Further randomized controlled trials are warranted to provide substantial evidence and to suggest combination strategies for treatment-resistant schizophrenia. PMID- 20309810 TI - Bupropion-associated premature ejaculation. PMID- 20309817 TI - [Editorial address at the beginning of the new decade]. PMID- 20309819 TI - Imaging of active multiple sclerosis plaques: efficiency of contrast-enhanced magnetization transfer subtraction technique. AB - PURPOSE: T1-weighted (T1W) magnetic resonance images with magnetization transfer (MT) are widely used in the evaluation of multiple sclerosis (MS) plaques. We aimed to evaluate the contribution of the subtraction technique with MT in the detection of acute MS plaques. MATERIALS AND METHODS: Sixty-four patients during an MS attack were enrolled in the study. Axial T1W spin echo (SE) with MT, axial sagittal T2W fast SE, axial FLAIR and postcontrast axial T1W SE magnetic resonance imaging sequence with MT were acquired from all patients. The subtraction (postcontrast-precontrast) images were obtained on the workstation. FLAIR and T2W images were used as reference for plaque imaging. Contrast material enhanced plaques were considered as acute plaques. Qualitatively, both subtracted and contrast-enhanced with MT images were evaluated visually. Quantitatively, signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) were calculated. RESULTS: A total of 464 plaques were detected on T2W and FLAIR images. Thirty five acute plaques were detected on both postcontrast MT and subtracted images. Additionally, 66 acute plaques were only detected on subtracted images visually. CNR and SNR values of acute MS plaques were significantly higher on subtracted MT images than on postcontrast MT images (P < 0.001). CONCLUSION: The subtraction technique seems to facilitate the detection of acute MS plaques by intensifying the visibility of poorly enhanced plaques without use of high dose contrast medium. We suggest the use of subtraction technique in routine imaging work-up of MS patients with acute attacks. PMID- 20309820 TI - Improvement of a popcorn population using selection indexes from a fourth cycle of recurrent selection program carried out in two different environments. AB - We estimated genetic gains for popcorn varieties using selection indexes in a fourth cycle of intrapopulation recurrent selection developed in the campus of the Universidade Estadual do Norte Fluminense. Two hundred full-sib families were obtained from the popcorn population UNB-2U of the third recurrent selection cycle. The progenies were evaluated in a randomized block design with two replications at sites in two different environments: the Colegio Estadual Agricola Antonio Sarlo, in Campos dos Goytacazes, and the Empresa de Pesquisa Agropecuaria do Estado do Rio de Janeiro (PESAGRO-RIO), in Itaocara, both in the State of Rio de Janeiro. There were significant differences between families within sets in all traits, indicating genetic variability that could be exploited in future cycles. Thirty full-sib families were selected to continue the program. The selection indexes used to predict the gains were those of Mulamba and Mock, Smith and Hazel. The best results were obtained with the Mulamba and Mock index, which allowed the prediction of negative gains for the traits number of diseased ears and ears attacked by pests, number of broken plants and lodging, as well as ears with poor husk cover. It also provided higher gains for popping expansion and grain yield than with the other indexes, giving values of 10.55 and 8.50%, respectively, based on tentatively assigned random weights. PMID- 20309821 TI - Overexpression of type-A rice response regulators, OsRR3 and OsRR5, results in lower sensitivity to cytokinins. AB - Response regulators are part of a two-component regulatory system. The type-A Arabidopsis response regulators act as negative regulators. To understand the function of type-A response regulators in the model monocot plant, rice (Japonica cultivar-group: Zhonghua11), we overexpressed two type-A OsRR genes, OsRR3 and OsRR5 (pACT1:OsRR3 and pACT1:OsRR5). We hoped to gain insight into their molecular function in cytokinin-signaling pathways. Both OsRR3 and OsRR5 overexpressors had longer roots and more lateral roots compared with Zhonghua11, when treated with exogenous cytokinin. Using callus formation and chlorophyll content assays, we found that Zhonghua11 was more sensitive to cytokinin compared with other cultivars of rice, expressing high transcript levels of OsRR3 and OsRR5. The expression of most type-A OsRR genes was repressed by OsRR3 and OsRR5 overexpression. However, semi-quantitative RT-PCR showed that three type-A OsRR genes showed increased expression. Our results suggest that both OsRR3 and OsRR5 mainly act as negative regulators of cytokinin signaling, as indicated by the reduced sensitivity of OsRR3 and OsRR5 overexpressors to exogenous cytokinins. PMID- 20309822 TI - Benefits of kinesiotherapy and aquatic rehabilitation on sickle cell anemia. A case report. AB - The process of hemoglobin polymerization and the consequent sickling of red blood cells that occurs in patients with sickle cell disease shortens the half-life of red blood cells. It causes vaso-occlusive complications, as well as pain and pulmonary and cardiovascular dysfunction. We evaluated an aquatic rehabilitation program used for patients with sickle cell anemia and examined the possible benefits that exercise in warm water has for the circulatory system, for relieving pain, and for increasing lung capacity. The patient was a 32-year-old female. The parameters that we used in this study include respiratory muscle strength (which was calculated by measuring maximum inspiratory pressures and maximum expiratory pressures), the McGill and Wisconsin pain questionnaires (in order to evaluate the patients' characterizations and descriptions of their pain), and the SF-36 Health Survey. The treatment included warm water exercises, stretching, aerobic exercise, and relaxation, during two sessions of 45 min per week for 5 weeks. The patient experienced a significant decrease in pain, a significant increase in the strength of respiratory muscles, and improved quality of life. We conclude that aquatic rehabilitation can be used to improve the clinical condition of sickle cell anemia patients, and we encourage more research on this new treatment regime, in comparison with other types of therapies. PMID- 20309823 TI - Karyotypic evolution trends in Rhamdia quelen (Siluriformes, Heptapteridae) with considerations about the origin and differentiation of its supernumerary chromosomes. AB - Among catfish species of the genus Rhamdia reported for the Brazilian territory, R. quelen is the most widespread, being found in nearly all hydrographic basins of Brazil. Nowadays, R. quelen is a synonym for at least 47 other species in this genus, its taxonomic status still being controversial. The available cytogenetic reports show a wide variation in the karyotypic macrostructure, with the frequent presence of supernumerary chromosomes. The remarkable cytogenetic variability associated with taxonomic issues in this species indicates that R. quelen is actually a species complex. In order to carry out a wide comparative cytogenetic study in R. quelen from southern and southeastern Brazil and examine a species complex, we analyzed the chromosomes of 14 populations from the main hydrographic basins of these two regions. Using classic and molecular cytogenetic techniques, we found seven distinct karyotypic formulae, all bearing 2n = 58 chromosomes. Supernumerary chromosomes were present in most of the populations; their number, size and C-banding pattern allowed us to differentiate populations with similar karyotypic compositions. We examined patterns of chromosomal evolution as well as the probable mechanisms involved in the origin and morphological differentiation of their supernumerary chromosomes. PMID- 20309824 TI - Optimization of DNA extraction from seeds and fresh leaf tissues of wild marigold (Tagetes minuta) for polymerase chain reaction analysis. AB - Tagetes, a genus of flowering marigolds in the family Asteraceae (Compositeae), is reported to be a medicinal plant with hypotensive, spasmolytic, anti inflammatory, antimicrobial, and antifungal properties. Tagetes minuta characteristically contains high concentrations of essential oils, flavonoids, polyphenols, and polysaccharides that interfere with DNA, causing erroneous or no PCR products. We tested and modified various standard protocols in an effort to isolate high-quality DNA from different plant tissues of T. minuta. We used sun dried, shade-dried and fresh-leaf tissues, as well as seeds for DNA analysis. The DNA obtained from seeds and fresh-leaf tissues with a modified cetyltrimethylammonium bromide buffer protocol was of good quality, with no colored pigments and contaminants. We were able to obtain good quality DNA from fresh leaf tissues without using liquid nitrogen. A relatively large amount of DNA was also extracted from the sun- and shade-dried tissues, but its quality was not as good as that from seeds. The DNA extracted from seeds and fresh leaves was successfully amplified by PCR using arbitrary RAPD primers. The same protocol will probably be useful for extracting high-molecular weight DNA from other plant materials containing large amounts of secondary metabolites and essential oils. PMID- 20309825 TI - Identifying the molecular basis of functions in the transcriptome of the social amoeba Dictyostelium discoideum. AB - The unusual life cycle of Dictyostelium discoideum, in which an extra-cellular stressor such as starvation induces the development of a multicellular fruiting body consisting of stalk cells and spores from a culture of identical amoebae, provides an excellent model for investigating the molecular control of differentiation and the transition from single- to multi-cellular life, a key transition in development. We utilized serial analysis of gene expression (SAGE), a molecular method that is unbiased by dependence on previously identified genes, to obtain a transcriptome from a high-density culture of amoebae, in order to examine the transition to multi-cellular development. The SAGE method provides relative expression levels, which allows us to rank order the expressed genes. We found that a large number of ribosomal proteins were expressed at high levels, while various components of the proteosome were expressed at low levels. The only identifiable transmembrane signaling system components expressed in amoebae are related to quorum sensing, and their expression levels were relatively low. The most highly expressed gene in the amoeba transcriptome, dutA untranslated RNA, is a molecule with unknown function that may serve as an inhibitor of translation. These results suggest that high-density amoebae have not initiated development, and they also suggest a mechanism by which the transition into the development program is controlled. PMID- 20309826 TI - Gelling agents and culture vessels affect in vitro multiplication of banana plantlets. AB - Agar is the most commonly used gelling agent in media for plant tissue culture. Because of the high price of tissue-culture-grade agar, attempts have been made to identify suitable alternatives. The type of culture vessel and lid also affects the gaseous composition inside the vessel as well as light penetration. In turn, the vessel affects growth parameters, such as shoot elongation, proliferation and fresh weight, as well as hyperhydric degradation processes. We examined the effects of different culture vessels, including commercial glass jars, magenta boxes, and disposable containers, as well as different gelling agents (agar-agar, Agargel, Phytagel, and plant agar) on the micropropagation of Dwarf Cavendish bananas in an effort to find a combination that yields large numbers of high-quality seedlings. The different culture vessels did not significantly affect seedling culture success. The medium significantly affected shoot weight. Phytagel resulted in the highest shoot weight (overall mean = 2.4 g), while agar, Agargel and plant agar resulted in 1.7, 2.2 and 2.2 g, respectively. Disposable container/Phytagel and Magenta/Agargel combinations yielded the highest shoot weights (2.9 and 3.0 g, respectively). Mean shoot length increased progressively with subculture (four subcultures were made). The highest mean shoot length was obtained with Phytagel and Agargel media (6.4 and 6.3 cm, respectively). Shoot number was significantly affected by medium only at subculture 4. Overall, the highest mean shoot length was obtained with the Magenta/Agargel combination (8.5 cm). Phytagel and plant agar gave higher mean shoot number than agar and Agargel (2.1, 2.1 and 1.7 and 1.9, respectively). The costs of the media and of the culture vessels need to be taken into account for final choice of the banana shoot culture system. PMID- 20309827 TI - Abnormal hemoglobin phenotypes in carriers of mild anemia in Latin America. AB - We looked for abnormal hemoglobins in blood samples sent for diagnosis of anemia. Identification of the hemoglobins was made using electrophoretic, chromatographic and molecular procedures. The 2020 blood samples were of patients from various regions of Brazil and from some other Latin American countries. Among the abnormal hemoglobins that we found, 3.5% are known to be rare, while 51% had an electrophoretic profile similar to that of Hb S at alkaline pH. Differentiation was possible only by combining electrophoretic and chromatographic methods. Hb Hasharon, an alpha globin chain mutant, was the most frequently found variant hemoglobin; it accounted for 14.3% of the abnormal DNA samples. The other abnormal hemoglobin phenotypes displayed distinct electrophoretic profiles; most of them migrated faster than Hb A. The frequencies of the different abnormal hemoglobin profiles that we found reflect the miscegenation of the Latin American population and indicate the importance of hemoglobin studies using various methods in combination for accurate diagnosis and appropriate counseling of carriers and their families. PMID- 20309828 TI - Karyological features of wild and cultivated forms of myrtle (Myrtus communis, Myrtaceae). AB - Myrtle is an evergreen shrub or small tree widespread throughout the Mediterranean region. In Turkey, both cultivated and wild forms, differing in plant and fruit size and fruit composition, can be found. These differences may have resulted from the domestication of the cultivated form over a long period of time. We investigated whether wild and cultivated forms of myrtle differ in karyological features (i.e., number of somatic chromosomes and relative genome size). We sampled two wild forms and six cultivated types of myrtle. All the samples had the same chromosome number (2n = 2x = 22). The results were confirmed by 4',6-diamidino-2-phenylindole (DAPI) flow cytometry. Only negligible variation (approximately 3%) in relative fluorescence intensity was observed among the different myrtle accessions, with wild genotypes having the smallest values. We concluded that despite considerable morphological differentiation, cultivated and wild myrtle genotypes in Turkey have similar karyological features. PMID- 20309829 TI - [Migraine and gestation: a complex relationship]. PMID- 20309830 TI - Serotonin transporter gene polymorphisms and auditory hallucinations in psychosis. AB - INTRODUCTION: To study the role of the serotonin transporter gene (SLC6A4) in the emotional processing of auditory hallucinations can be particularly important to better understand the pathophysiology of auditory hallucinations. Moreover, a poly-morphism located in this gene (5-HTTLPR) has been previously associated with different disorders related to altered emotional responses. The aim of this study was to evaluate the relationship between different polymorphisms of the SLC6A4 gene and different aspects of auditory hallucinations in schizophrenic patients, with a special consideration toward the emotional response to auditory hallucinations. SUBJECTS AND METHODS: Two samples of 224 patients with auditory hallucinations and 346 healthy subjects were studied. AH were assessed in patients through the PSYRATS scale for auditory hallucinations. Several polymorphisms located within the SLC6A4 gene were analysed through case-control comparisons as well as association analyses with different parameters of auditory hallucinations. RESULTS: No differences were found between patients and controls for any of the analysed polymorphisms (p > 0.05). However, the evaluation of auditory hallucinations parameters showed that the low expressing alleles of the 5-HTTLPR polymorphism were associated with higher levels of intensity of the distress caused by auditory hallucinations (p = 0.049 corrected for the item 'intensity of distress'). There was also a trend with the parameter disruption (p = 0.06 corrected). These two items of the PSYRATS scale are directly related to the emotional dimension of auditory hallucinations. In contrast, we did not observe any association with items related to other dimensions of auditory hallucinations. CONCLUSIONS: Our results support a possible role of the serotonin transporter in the emotional response to auditory hallucinations. PMID- 20309831 TI - [Usefulness of the Stroop test in attention deficit hyperactivity disorder]. AB - AIMS: The aim of this study is to analyse the differences in the Stroop effect between cases with attention deficit hyper-activity disorder (ADHD) and controls. It also seeks to find the best model based on the third task of the colours and words test (Stroop-CW) for predicting ADHD and to analyse the validity of the Stroop-CW test for diagnosing the disorder. SUBJECTS AND METHODS: The sample studied consisted of 100 cases of ADHD -according to Diagnostic and statistical manual of mental disorders (DSM-IV) criteria- and 100 controls, between 7 and 11 years of age, who were evaluated using the Stroop test. The controls were recruited at random and paired by age, sex and sociodemographic area with the cases. RESULTS: The cases present a mean cognitive style that is significantly less flexible (d = -1.06) and they also display a lower capacity to inhibit or control automatic responses than the controls at all ages (7 years: d = 1.67; 8 years: d = 1.02; 9 years: d = 1.32; 10 years: d = 2.04; 11 years: d = 0.89). The model of logistic regression analysis that best predicts ADHD is made up of age and Stroop-CW. The formulation derived from the model offers a sensitivity of 81% and a specificity of 72%, taking the criteria of the DSM-IV for ADHD as the reference test. CONCLUSIONS: The Stroop-CW test presents usefulness and complementary criteria validity for the diagnosis of ADHD. PMID- 20309832 TI - [Mesial temporal sclerosis in paediatrics: its clinical spectrum. Our experience gained over a 19-year period]. AB - INTRODUCTION: Mesial temporal sclerosis (MTS) is defined as neuron loss and gliosis in the hippocampus and adjacent structures. Here we report on our 19 years' experience in dealing with this condition. PATIENTS AND METHODS: A retrospective, descriptive study was conducted of patients diagnosed with MTS between May 1990 and January 2009. RESULTS: A diagnosis of MTS was established in 16 cases (62.5% males). By location these cases were distributed as follows: 12 were unilateral (seven left temporal and five right) and four were bilateral. It was associated to cortical dysplasia in six patients (37.5%) and to hippocampal arachnoid cysts in two other cases. As regards possible causations, in one case herpes simplex encephalitis was suspected; in three cases, a prenatal cerebral vascular pathology; and in three others, prenatal infection by cytomegalovirus. The distribution of the clinical spectrum was as follows: five patients with isolated clinical epilepsy; one with isolated psychomotor retardation or mental retardation (PMR-MR); one with isolated autism spectrum disorder (ASD); three with epilepsy associated to PMR-MR; one with epilepsy associated to ASD; two with PMR-MR and ASD; and two with the triad consisting of epilepsy together with PMR MR and ASD. In one case, MTS was discovered in migraine studies, without any other symptoms. Crises were controlled with monotherapy in all the patients who received antiepileptic treatment except in three, one of whom required surgery. CONCLUSIONS: The definitive diagnosis of MTS is pathologic, but the latest neuroimaging techniques have allowed a very reliable approximate diagnosis to be reached. It may be associated to other malformative disorders, such as focal cortical dysplasia or cysts. MTS can be observed in epilepsy (whether refractory or not), but also in ASD, PMR-MR or asymptomatic patients. PMID- 20309833 TI - [Inflammation as a therapeutic agent in cerebral infarction: cellular inflammatory response and inflammatory mediators]. AB - INTRODUCTION: The immune central nervous system (CNS) innate immune cells including microglia and macrophages play integral roles in receiving and propagating inflammatory signals. Inflammation is generally a beneficial response of an organism to infection but, when prolonged or inappropriate, it can be detrimental. Neuronal loss in acute (e.g. stroke and head injury) and chronic (e.g. multiple sclerosis and Alzheimer's disease) CNS diseases has been associated with inflammatory processes systemically and in the brain. DEVELOPMENT: Herein we review the processes that participate in the activation of the immune system and the starting of inflammatory response after stroke, where neuronal necrotic cell death has been described. We addressed the relevance of the innate inflammatory cells that are on the CNS, as microglia and macrophages, which have an important role in receiving and spreading inflammatory signals. In addition, the inflammatory response is characterized by an increase in the levels of expression of inflammatory mediators, which regulate adhesion molecules, and increase the permeability of the blood-brain barrier. It has also been described that inflammation promotes the rapid over-expression and activation of a variety of genes, and it has been postulated that transcription factors should be studied for their potential use in therapeutics and repair. Transcriptional activation can be a double-edged sword since depending on the individual transcription factor it can induce the expression of either neuroprotective or neurotoxic genes. CONCLUSION: In summary, a better understanding of the different molecules mediating the immune response will allow the design of new pharmacological tools that could improve stroke treatment. PMID- 20309834 TI - [Genetics of Alzheimer's disease]. AB - INTRODUCTION AND DEVELOPMENT. Alzheimer's disease (AD), the leading cause of dementia, is a complex disorder in which genetic and environmental factors interact. Three genes -the amyloid precursor protein (APP) and the presenilin 1 and 2 (PSEN1 and PSEN2)- have been linked to autosomal dominant forms of AD. Besides, a fourth gene -the apolipoprotein E gene (APOE)- seems to be the only major genetic factor related to late-onset sporadic and familial AD cases. Although more than a thousand studies have been performed to date, little is known about other genetic factors leading to this devastating dementia. Nevertheless, the last three years have witnessed a surge in genetic research of AD due to the implementation of novel technologies enabling large-scale genetic analyses. CONCLUSION. This review provides a summary of current knowledge about AD in the genetic field. PMID- 20309835 TI - [De secretis mulierum, de chirurgia et de modo medendi libri septem. Neurology and women in mediaeval medical literature]. AB - INTRODUCTION AND AIMS: The School of Salerno stood as a landmark in the teaching and practice of medicine in the Western mediaeval world. Women could be both teachers and students and made significant contributions to its abundant scientific production. One of the most important of such women was Trotula of Salerno, the 12th century author of the Passionibus mulierum curandorum. De secretis mulierum, de chirurgia et de modo medendi libri septem is an anonymous medical poem from the School of Salerno, which was discovered in a manuscript from the 13th century. It consists of seven books and 7280 dactylic hexameters. The first book is specifically devoted to women's diseases and the second is a treaty on cosmetics. Books III and IV deal with surgery and follow the classical a capite ad calcem formula. The seventh book, De modo medendi, deals with therapeutics. We review the references to neurological diseases, using a critical translation of this text to carry out our study. DEVELOPMENT: The poem proposes therapies to treat epilepsy, headache or tinnitus. The treatment to be prescribed for headache differs depending on its origin. It puts forward pathophysiological explanations for the different types of headache, it relates engorged blood vessels with hemicranial headache, and suggests an excess of phlegm as the origin of mild occipital headache. CONCLUSIONS: Neurological pathology is well represented in this mediaeval monograph on women's diseases. Furthermore, it also shows us the vision that the Salerno physician has of these conditions and the therapeutic arsenal (based mainly on medicinal plants) that was available for use. PMID- 20309837 TI - [Germinoma with tetraventricular extension: the importance of biopsy studies in germinal tumours in the nervous system]. PMID- 20309838 TI - [Infarction from air embolism secondary to intestinal ischaemia]. PMID- 20309839 TI - [Nutrition and attention-deficit/hyperactivity disorder]. PMID- 20309840 TI - Orthogonal predictions: follow-up questions for suggestive data. AB - When a biological hypothesis of causal effect can be inferred, the hypothesis can sometimes be tested in the selfsame database that gave rise to the study data from which the hypothesis grew. Valid testing happens when the inferred biological hypothesis has scientific implications that predict new relations between observations already recorded. Testing for the existence of the new relations is a valid assessment of the biological hypothesis, so long as the newly predicted relations are not a logical correlate of the observations that stimulated the hypothesis in the first place. These predictions that lead to valid tests might be called 'orthogonal' predictions in the data, and stand in marked contrast to 'scrawny' hypotheses with no biological content, which predict simply that the same data relations will be seen in a new database. The Universal Data Warehouse will shortly render moot searches for new databases in which to test. PMID- 20309841 TI - Lipid peroxidation in the kidney of rats treated with V and/or Mg in drinking water. AB - Spontaneous and stimulated lipid peroxidation (LPO) after vanadate and magnesium treatment was studied in kidney supernatants obtained from outbred 5-month-old, albino male Wistar rats. The 2-month-old animals daily received: group I (control), deionized water to drink; group II, water solution of sodium metavanadate, NaVO(3) (SMV, 0.125 mg V ml(-1)); group III, water solution of magnesium sulfate, MgSO(4) (MS, 0.06 mg Mg ml(-1)); and group IV, water solution of SMV-MS at the same concentrations as in groups II and III for V and Mg, respectively, over a 12-week period. FeSO(4), NaVO(3) and MgSO(4) were selected as agents that may modify LPO process in in vitro conditions. Spontaneous malondialdehyde (MDA) levels in kidney supernatants increased significantly in the rats in groups II and IV, compared with groups I and III; and they were also significantly higher in all the groups of rats compared with the liver supernatants. The total antioxidant status (TAS) in groups II and IV tended to be higher too. Vanadium concentration in the kidney of the rats in groups II and IV increased, whereas the kidney Mg content in groups II, III and IV decreased, compared with levels in the liver. As the two-way ANOVA indicated, the changes in the basal MDA level, TAS and Mg concentration in the liver of rats at combined V and Mg application only resulted from independent action of V. As far as the in vitro results are concerned, in the supernatants obtained from the rats in groups II and IV, a significant increase in MDA level was demonstrated in the presence of 30 microm of exogenous FeSO(4) as well as 30, 100, 200 and 400 microm NaVO(3) and 100, 200, 400, 600, 800 and 1000 microm MgSO(4), compared with groups I and III. The 600, 800 and 1000 microm of exogenous MgSO(4) also significantly elevated MDA production in the supernatants obtained from the rats in group III, compared with spontaneously formed MDA in the same supernatants. The three-way ANOVA showed that the changes in LPO induced by in vitro treatment of kidney supernatants with exogenous Fe or V or Mg (600, 800 and 1000 microm) were a consequence of independent action of those metals and they also resulted from the interactions between exogenous Fe (Fe(exog)) and endogenous V (V(end)) and between V(end) and exogenous V (V(exog)). In conclusion, V (as NaVO(3)) consumed by the rats with drinking water at a dose of 12.9 mg V kg(-1) b.w. per 24 h for 12 weeks increased the basal LPO and markedly enhanced TAS in the renal tissue. Its pro-oxidant potential was also found in in vitro conditions. The Mg dose (6 mg Mg kg(-1) b.w. per 24 h) ingested by the rats together with V (12.7 mg V kg( 1) b.w. per 24 h) neither reduced nor intensified the spontaneous LPO, compared with V-only intoxicated animals; however, the stimulating effect of Mg on LPO was revealed in in vitro conditions. PMID- 20309842 TI - Inter-rater reliability of the Structured Clinical Interview for DSM-IV Axis I Disorders (SCID I) and Axis II Disorders (SCID II). AB - This study simultaneously assessed the inter-rater reliability of the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders Axis I (SCID I) and Axis II disorders (SCID II) in a mixed sample of n = 151 inpatients and outpatients, and non-patient controls. Audiotaped interviews were assessed by independent second raters blind for the first raters' scores and diagnoses. Categorical inter-rater reliability was assessed for 12 Axis I disorders of SCID I, while both categorical and dimensional inter-rater reliability was tested for all Axis II disorders. Results revealed moderate to excellent inter-rater agreement of the Axis I disorders, while most categorically and dimensionally measured personality disorders showed excellent inter-rater agreement. PMID- 20309843 TI - Bacopa monniera (L.) wettst inhibits type II collagen-induced arthritis in rats. AB - Bacopa monniera (L.) Wettst is an Ayurvedic herb with antirheumatic potential. This study investigated the therapeutic efficacy of Bacopa monniera in treating rheumatoid arthritis using a type II collagen-induced arthritis rat model. Arthritis was induced in male Wistar rats by immunization with bovine type II collagen in complete Freund's adjuvant. Bacopa monniera extract (BME) was administered after the development of arthritis from day 14 onwards. The total duration of experiment was 60 days. Paw swelling, arthritic index, inflammatory mediators such as cyclooxygenase, lipoxygenase, myeloperoxidase and serum anti collagen IgG and IgM levels were analysed in control and experimental rats. Arthritic induction significantly increased paw edema and other classical signs of arthritis coupled to upregulation of inflammatory mediators such as cyclooxygenase, lipoxygenase, neutrophil infiltration and increased anti-collagen IgM and IgG levels in serum. BME significantly inhibited the footpad swelling and arthritic symptoms. BME was effective in inhibiting cyclooxygenase and lipoxygenase activities in arthritic rats. Decreased neutrophil infiltration was evident from decreased myeloperoxidase activity and histopathological data where an improvement in joint architecture was also observed. Serum anti-collagen IgM and IgG levels were consistently decreased. Thus the study demonstrates the potential antiarthritic effect of Bacopa monniera for treating arthritis which might confer its antirheumatic activity. PMID- 20309844 TI - Corrective osteotomy using customized hydroxyapatite implants prepared by preoperative computer simulation. AB - BACKGROUND: Opening wedge corrective osteotomy usually requires a bone graft. However, it is difficult to shape the graft into an appropriate configuration. To resolve this problem, we developed an original computer program system that calculates the size and shape of a bone graft and cuts a hydroxyapatite block into the desired shape. METHODS: Five patients with forearm deformity were included in this study. The amount of deformity and the three-dimensional (3D) shape of the bone graft to be inserted into the osteotomy site were calculated and designed by comparing bilateral 3D bone models. For the bone graft, a block of hydroxyapatite was cut based on the preoperative simulation. In addition, a customized osteotomy template was designed and manufactured before surgery, based on preoperative simulations and used during the actual operation. RESULTS: Corrective osteotomy based on simulations was achieved in all cases. The average angular deformities on anteroposterior and lateral radiographs were decreased from 16.8 degrees to 1.2 degrees and from 16.6 degrees to 0.6 degrees, respectively, after surgery. All patients had bone fusion within 5 months. CONCLUSIONS: Customized hydroxyapatite implants are helpful for accurate correction and good functional results. PMID- 20309845 TI - New tactile sensing system for minimally invasive surgical tumour localization. AB - BACKGROUND: Minimally invasive surgery (MIS) suffers from the inability to directly palpate organs for tumour localization. A tactile sensing system (TSS), consisting of a probe and a visualization interface, was developed to present an active pressure map of the contact surface to locate tumours during MIS. METHODS: The TSS performance was compared to MIS graspers to locate occult 10 mm phantom tumours in ex vivo bovine liver and ex vivo porcine lung. Performance assessment included applied pressure, localization distance and accuracy. RESULTS: The TSS realized a relative 71% reduction in maximum applied pressure and a 31% increase in detection accuracy in liver tissue (when compared to MIS graspers) and demonstrated no significant differences in performance when palpating lung tissue. CONCLUSIONS: The TSS may help surgeons to identify occult tumours during surgery by restoring some of the haptic information lost during MIS. PMID- 20309846 TI - Increased risk of high-grade prostate cancer among infertile men. AB - BACKGROUND: It has been reported that fatherhood status may be a risk factor for prostate cancer. In the current study, the authors examined the subsequent occurrence of prostate cancer in a cohort of men evaluated for infertility to determine whether male infertility is a risk factor for prostate cancer. METHODS: A total of 22,562 men who were evaluated for infertility from 1967 to 1998 were identified from 15 California infertility centers and linked to the California Cancer Registry. The incidence of prostate cancer was compared with the incidence in an age-matched and geography-matched sample of men from the general population. The risk of prostate cancer in men with and those without male factor infertility was modeled using a Cox proportional hazards regression model. RESULTS: A total of 168 cases of prostate cancer that developed after infertility were identified. Men evaluated for infertility but not necessarily with male factors were not found to have an increased risk of cancer compared with the general population (standardized incidence ratio [SIR], 0.9; 95% confidence interval [95% CI], 0.8-1.1). This risk was found to be highest for men with male factor infertility who developed high-grade prostate cancer (SIR, 2.0; 95% CI, 1.2-3.0). On multivariate analyses, men with male factor infertility were found to be 2.6 times more likely to be diagnosed with high-grade prostate cancer (hazard ratio, 2.6; 95% CI, 1.4-4.8). CONCLUSIONS: Men with male factor infertility were found to have an increased risk of subsequently developing high grade prostate cancer. Male infertility may be an early and identifiable risk factor for the development of clinically significant prostate cancer. PMID- 20309847 TI - Race versus place of service in mortality among medicare beneficiaries with cancer. AB - BACKGROUND: Evidence suggests that excess mortality among African-American cancer patients is explained in part by the healthcare setting. The objective of this study was to compare mortality among African-American and Caucasian cancer patients and to evaluate the influence of attendance at a National Cancer Institute (NCI)-designated comprehensive or clinical cancer center. METHODS: The authors conducted a retrospective cohort analysis of Medicare beneficiaries with an incident diagnosis of lung, breast, colorectal, or prostate cancer between 1998 and 2002 who were identified from Surveillance, Epidemiology, and End Results data. Multivariate logistic regression models were used to assess the impact of NCI cancer center attendance and race on all-cause and cancer-specific mortality at 1 year and 3 years after diagnosis. RESULTS: The likelihood of 1 year and 3-year all-cause and cancer-specific mortality was higher for African Americans than for Caucasians in crude and adjusted models (cancer-specific adjusted: Caucasian referent, 1-year odds ratio [OR], 1.13; 95% confidence interval [CI], 1.07-1.19; 3-year OR, 1.23; 95% CI, 1.17-1.30). By cancer site, cancer-specific mortality was higher among African Americans at 1 year for breast and colorectal cancers and for all cancers at 3 years. NCI cancer center attendance was associated with significantly lower odds of mortality for African Americans (1-year OR, 0.63; 95% CI, 0.56-0.76; 3-year OR, 0.71; 95% CI, 0.62 0.81). With Caucasians as the referent group, the excess mortality risk among African Americans no longer was observed for all-cause or cancer-specific mortality risk among patients who attended NCI cancer centers (cancer-specific mortality:1-year OR, 0.95; 95% CI, 0.76-1.19; 3-year OR, 1.00; 95% CI, 0.82 1.21). CONCLUSIONS: African-American Medicare beneficiaries with lung, breast, colorectal, and prostate cancers had higher mortality compared with their Caucasian counterparts; however, there were no significant differences in mortality by race among those who attended NCI cancer centers. The results of this study suggested that place of service may explain some of the cancer mortality excess observed in African Americans. PMID- 20309848 TI - Covariation of self- and other-directed aggression among inpatient youth: continuity in the transition to treatment and shared risk factors. AB - Although other- and self-directed aggression covary in very high-risk youth, these forms of aggression infrequently are studied simultaneously. Understanding better their covariation is an important task for improving services to high-risk youth. In this study, data from the clinical records of 476 youth admitted to secure inpatient treatment were analyzed to examine relations among self- and other-directed aggression exhibit before and during inpatient treatment. Analyses tested the hypotheses that self- and other-directed aggression would tend to covary and display continuity from pre-treatment to in-treatment. Also tested were the hypotheses that youth with histories of co-occurring self- and other directed aggression would show the highest levels of aggression during treatment and the greatest degree of personal and contextual risk on entering treatment. These hypotheses were largely supported. Exploratory analyses revealed interesting discontinuities in aggression (aggression emitted only before or during treatment) with critical implications for research and practice with youth receiving clinical care, especially those in institutional placements. PMID- 20309849 TI - Prey capture in frogs: alternative strategies, biomechanical trade-offs, and hierarchical decision making. AB - Frogs exhibit flexible repertoires of prey-capture behavior, which depend primarily on visual analysis of prey attributes. We review three examples of how visual cues are used to modulate prey-capture strategies. (1) Dyscophus guineti modulates tongue aiming in response to prey location. These frogs turn only their heads to apprehend prey located at azimuths <40 degrees . At azimuths >40 degrees , the frogs switch from this strategy to one in which both head and tongue are aimed toward prey. (2) Rana pipiens modulates its feeding behavior in response to prey size, using tongue prehension for capturing small prey but switching to jaw prehension to capture large prey. (3) In Cyclorana novaehollandiae, visual processing of prey attributes involves hierarchical decision making. These frogs first assess prey size. For large prey, they ignore velocity but not shape. For small prey, they ignore shape but not velocity. Alternative prey-capture strategies are associated with biomechanical trade-offs that result from the interaction between the feeding apparatus and varying attributes of prey. Alternative strategies likely exist because biomechanical constraints prevent any one strategy from being effective over a range of prey attributes. Taken together, these studies emphasize the requirement that predators must somehow tune prey-capture kinematics simultaneously to multiple attributes of prey. In frogs, the choice among alternative prey-capture strategies involves a hierarchical decision-making process. Hierarchical decision making is expected to be widespread among animals. However, no previous studies were found except for humans, who frequently use this type of approach to make complex decisions. PMID- 20309850 TI - Compatibility of traditional and novel acaricides with bumblebees (Bombus terrestris): a first laboratory assessment of toxicity and sublethal effects. AB - BACKGROUND: This project assessed the potential hazards of different classical and novel acaricides against an important non-target and beneficial insect for the pollination of wild flowers and cultivated crops, the bumblebee Bombus terrestris (L). Twenty-three acaricides used commercially in the control of phytophagous mites (Acari) were tested in greenhouses and/or the open field. Side effects included acute mortality and also sublethal effects on nest reproduction. The different compounds were administered in the laboratory via three different worst-case field scenario routes of exposure: dermal contact and orally via the drinking of treated sugar water and via treated pollen. The compounds were tested at their respective maximum field recommended concentration (MFRC), and, when strong lethal effects were observed, a dose-response assay with a dilution series of the MFRC was undertaken to calculate LC(50) values. RESULTS: From the different acaricide classes, several chemistries caused high levels of acute toxicity in bumblebee workers, especially bifenthrin and abamectin which resulted in 100% mortality by contact. In addition, several acaricides tested were found to have a detrimental effect on drone production. For oral exposures via treated sugar water, the dose-response assay showed the LC(50) values for abamectin, bifenazate, bifenthrin and etoxazole to be 1/15 MFRC (1.17 mg AI L(-1)), 1/10 MFRC (9.6 mg AI L(-1)), 1/83 MFRC (0.36 mg AI L(-1)) and 1/13 MFRC (4.4 mg AI L( 1)) respectively, indicating that their use should be carefully evaluated. CONCLUSION: Overall, the results suggest that most of the acaricides tested are compatible with bumblebees, with the exceptions of abamectin, bifenazate, bifenthrin and etoxazole. However, the risks also depended on the type of treatment. As a result, the sugar water treatment seems to present the worst-case situation of exposure, indicating that this approach is suitable for determining the hazards of pesticides against bumblebees. Finally, it is suggested that future tier testing under more field-related conditions is required for a final decision of their risks. PMID- 20309851 TI - Use of rat segmental intestine for fetal pancreatic transplantation. AB - It is thought that the small intestine may provide a scaffold for pancreas regeneration. Herein, we investigated whether fetal pancreatic tissue could be transplanted into the segmental intestine in rats. Fetal pancreases from firefly luciferase transgenic Lewis rat embryos (embryonic day 14.5 and 15.5) were transplanted into streptozotocin (STZ)-induced diabetic wild-type Lewis rats. As a scaffold for pancreatic development, rat small intestinal segments were utilized after the removal of mucosa, and fetal pancreases were grafted into the luminal surface through the stoma. We also transplanted fetal pancreases into the omentum. The survival of transplanted fetal pancreases was monitored by luciferase-derived photons and blood glucose levels. Transplanted fetal pancreas derived photons were stable for 28 days, suggesting that transplanted fetal pancreatic tissues survived and that their intestinal blood supply was maintained. PMID- 20309852 TI - Improvement of the skin flap survival with the bone marrow-derived mononuclear cells transplantation in a rat model. AB - Partial necrosis of skin flaps remains a significant problem in plastic and reconstructive surgery. In this study we attempted to evaluate the effect of bone marrow-derived mononuclear cells (BM-MNCs) transplantation on improvement of skin flap survival in a rat random pattern skin flap model. Thirty Wistar rats were divided into three groups with each consisting of 10 rats. BM-MNCs and the adipose-derived stem cells (ADSCs) were transplanted into the subcutaneous tissue in the area where the flap would be dissected. The flaps were then raised two days after cells transplantation. The animals receiving the preoperative Dulbecco's Modified Eagle Medium (DMEM) treatment were used as the controls. On the 7th postoperative day, the survival areas of flaps were measured and tissues were collected for examinations. The results showed that the mean survival areas were 46.33 +/- 13.46% in the ADSCs group and 50.06 +/- 13.82% in the BM-MNCs group as the percentages of the total skin flaps, which were significantly higher than that in the control group (26.33 +/- 7.14%) (P < 0.05). Histological analysis showed increased neovascularization in the flap treated with BM-MNCs when compared with ADSCs transplantation. Survival BM-MNCs and ADSCs were detected in the flap tissues. Higher levels of the basic fibroblast growth factor (bFGF) and vascular endothelium growth factor (VEGF) were found in the BM-MNCs transplantation group (P < 0.05). The findings from this study demonstrated that preoperative treatment with BM-MNCs transplantation could promote neovascularization and improve flap survival. These effects of BM-MNCs on flap survival were comparable with ADSCs transplantation, but without necessity of in vitro cells expansion. PMID- 20309853 TI - Development of a portocaval shunt using a small intestinal segment in rats. AB - The transjugular portosystemic shunt, widely used to treat portal hypertension today, may increase the risk of encephalopathy and reduce effective hepatic flow. To address these issues, a strategy to produce a portocaval shunt (PCS) with hepatic function using intestinal grafts was conceived, and rat models were developed. We transplanted ileal grafts from wild-type and luciferase transgenic Lewis rats to wild-type Lewis rats, anastomosing the graft mesenteric artery (SMA) and portal vein (PV) to the recipient PV trunk and inferior vena cava, respectively. Recipient survival was significantly longer in the partial PCS model, in which the graft SMA was anastomosed to the recipient PV trunk in an end to-side fashion, than in the total PCS model, with the end-to-end anastomosis. In the partial PCS model, histological and luminescence analyses showed graft survival for 1 month. These results suggest that intestinal grafts can be maintained in the particular conditions required for our strategy. PMID- 20309854 TI - Primary high-grade ocular adnexal lymphoma: clinicopathological characteristics and prognostic factors of a single-centre series. PMID- 20309855 TI - Low cobalamin levels associated with sickle cell disease: Contrasting origins and clinical meanings in two instructive patients. PMID- 20309857 TI - Semi-micro flow injection analysis method for evaluation of quenching effect of health foods or food additive antioxidants on peroxynitrite. AB - A semi-micro flow injection analysis (SMFIA) method for evaluation of quenching effect of food additive antioxidants or health foods on peroxynitrite (ONOO(-)) is described. The injected sample was carried with phosphate buffer containing NaNO(2), mixed with a trigger solution to generate ONOO(-) and then detected CL generated after mixing with luminol solution. Selective chemiluminescence caused by ONOO(-) in this generation system was confirmed by catalase treatment. Ascorbic acid (ASA), Trolox and ascorbyl palmitate (ASP) were used as food additive antioxidants. EC(50) values of ASA, Trolox and ASP were 2.6, 6.4 and 43 ug/mL, respectively. The amount of reagents required for an assay by this SMFIA system could reduce the time by a third compared with the conventional method previously reported. Furthermore, as an application of the proposed method, the quenching effect of commercially available Noni (Morinda citrifolia) juices was evaluated. PMID- 20309856 TI - Laboratory tests for protein C deficiency. AB - Hereditary protein C deficiency is a hypercoagulable state associated with an increased risk for venous thrombosis. The recommended initial test for protein C is an activity (functional) assay, which may be clotting time based or chromogenic. The advantages and disadvantages of the various testing options are presented. The causes of acquired protein C deficiency are much more common than hereditary deficiency. Therefore, this article describes the appropriate steps to take when protein C activity is low, to confirm or exclude a hereditary deficiency. The causes of falsely normal results are also described, including lupus anticoagulants and direct thrombin inhibitors. PMID- 20309858 TI - Electrochemiluminescence of palmatine being oxidized by electrogenerated hydroxyl radical and its analytical application. AB - A strong electrochemiluminescence (ECL) of palmatine in NaOH medium was observed at a vaseline-impregnated graphite anode. The ECL production could be described as follows: hydroxyl radical (OH(*)) was generated via the oxidation of hydroxyl group (OH(-)) in NaOH medium, and the formed OH(*) subsequently oxidized palmatine base converted from palmatine in NaOH medium to the excited state oxypalmatine (oxypalmatine*). As the oxypalmatine* went back to its ground state, a stronger chemiluminescence was produced. Based on the ECL of palmatine, an ECL method for the determination of palmatine was proposed. An ECL signal of palmatine in NaOH solution was obtained by applying direct current of 15 mA to the vaseline-impregnated graphite anode. The ECL intensity was rectilinear with palmatine concentration in the range of 8.0 * 10(-7) to 2.0 * 10(-5) mol l(-1) and the limit of detection (signal-to-noise = 3) was 3 * 10(-7) mol l(-1) . The proposed method was applied to the determination of palmatine in pharmaceutical preparations. PMID- 20309859 TI - Study on the interaction between human serum albumin and a novel bioactive acridine derivative using optical spectroscopy. AB - The interaction of a novel bioactive agent N-{[N-(2-dimethylamino) ethyl] acridine-4-carboxamide}-alpha-alanine [N-(ACR-4-CA)-alpha-ALA] with human serum albumin (HSA) was investigated by fluorescence spectroscopy, UV-vis absorption and circular dichroism spectrophotometric techniques under simulative physiological conditions. The fluorescence quenching of HSA by addition of N-(ACR 4-CA)-alpha-ALA is due to static quenching and hydrogen bonding. Moreover, hydrophobic interactions play a role in the binding of N-(ACR-4-CA)-alpha-ALA to HSA as well. The number of binding sites, n, and the binding constant values, K(A), were noted to be 0.88 and 3.4 * 10(4) L mol(-1) for N-(ACR-4-CA)-alpha-ALA at 293 K. The binding distances and the energy transfer efficiency between N-(ACR 4-CA)-alpha-ALA and protein were determined. The negative value of enthalpy change and positive value of entropy change in the present study indicated that both hydrogen bonding and hydrophobic forces played a major role in the binding of N-(ACR-4-CA)-alpha-ALA to HSA. PMID- 20309860 TI - Precise landmarking in computer assisted total knee arthroplasty is critical to final alignment. AB - Image-free computer navigation systems build a frame of reference of a patient's knee from anatomical landmarks entered by the surgeon during the initial stage of total knee arthroplasty. We performed tibial cuts on 70 sawbones using computer navigation. All landmarks were marked identically except for the tibial mechanical entry point, which was marked correctly in 10 bones and with offsets of 5, 10, and 15 mm medially and laterally in the others. The actual coronal angle of the tibial cuts was measured directly and compared to the final angle given by the navigation system. Significant deviations of the coronal angle were observed in the trial groups. Landmarking errors during navigated TKA can lead to inaccurate tibial bone cuts. This navigation system did not have an iterative software method to verify landmarking errors that can lead to inaccurate tibia bone cuts. PMID- 20309861 TI - Analysis of frictional behavior and changes in morphology resulting from cartilage articulation with porous polyurethane foams. AB - Porous polyurethane foams (PUR) have been extensively evaluated as meniscal replacement materials and show great promise enabling infiltration of cells and fibrocartilage formation in vivo. Similar to most materials, PUR demonstrates progressive degeneration of opposing cartilage; however, the damage mechanism is impossible to determine because no information exists on the frictional properties of PUR-cartilage interfaces. The goals of this study were to characterize the frictional behavior of a cartilage-PUR interface across a range of articulating conditions and assess the resulting morphological changes to the cartilage surface following articulation. Articular cartilage was oscillated against PUR or stainless steel using phosphate-buffered saline (PBS) and synovial fluid as lubricants. Following friction testing, cartilage and PUR samples were analyzed with environmental scanning electron microscopy and histological staining to determine changes in tissue morphology. Stribeck-surface analysis demonstrated distinct lubrication modes; however, boundary mode lubrication was dominant in cartilage-PUR interfaces and the low-friction pressure-borne lubrication mechanism present in native joints was absent. Microscopy noted obvious wear, with disruption of the collagen architecture and concomitant proteoglycan loss in cartilage articulated against PUR. These data collectively point to the importance of frictional properties as design parameters for implants and materials for soft tissue replacement. PMID- 20309862 TI - Breaking T cell tolerance against self type II collagen in HLA-DR4-transgenic mice and development of autoimmune arthritis. AB - OBJECTIVE: To establish a new animal model in DRB1*0401 (DR4)-transgenic mice in which T cell tolerance to self type II collagen (CII) can be broken and allow for the development of autoimmune arthritis, to investigate the role of posttranslational modifications of the CII(259-273) epitope in the induction and breaking of tolerance of DR4-restricted T cells, and to characterize DR4 restricted T cell recognition of the immunodominant CII(259-273) epitope. METHODS: DR4-transgenic mice expressing either the entire human CII protein (HuCII) or only the immunodominant T cell epitope of heterologous CII (MMC) in joint cartilage were established on different genetic backgrounds, and susceptibility to collagen-induced arthritis (CIA) was tested. RESULTS: HuCII mice displayed stronger T cell tolerance to heterologous CII than did MMC mice. On the B10 background, arthritis developed only in MMC mice with a defective oxidative burst. However, MMC mice on the C3H background were susceptible to arthritis also with a functional oxidative burst. Significant recall responses in tolerized mice were detected only against the nonglycosylated CII(259-273) epitope. Recognition of the CII(259-273) epitope was heterogeneous, but the majority of T cells in DR4 mice specifically recognized the nonglycosylated side chain of lysine at position 264. CONCLUSION: It is possible to break tolerance to self CII and induce arthritis in DR4 mice. However, arthritis susceptibility is tightly controlled by the genetic background and by the source of the transgenic element for expressing the heterologous CII peptide as a self CII protein in the joint. In contrast to CIA in A(q)-expressing mice, the nonglycosylated CII(259 273) epitope is clearly immunodominant in both tolerized and nontolerized DR4 mice. PMID- 20309863 TI - Does pregnancy provide vaccine-like protection against rheumatoid arthritis? AB - OBJECTIVE: Previous studies have evaluated the correlation between rheumatoid arthritis (RA) risk and pregnancy history, with conflicting results. Fetal cells acquired during pregnancy provide a potential explanation for modulation of RA risk by pregnancy. The present study was undertaken to examine the effect of parity on RA risk. METHODS: We examined parity and RA risk using results from a population-based prospective study in Seattle, Washington and the surrounding area and compared women who were recently diagnosed as having RA (n = 310) with controls (n = 1,418). We also evaluated the distribution of parity in cases according to HLA genotype. RESULTS: We found a significant reduction of RA risk associated with parity (relative risk [RR] 0.61 [95% confidence interval 0.43 0.86], P = 0.005). RA risk reduction in parous women was strongest among those who were younger. Most striking was that RA risk reduction correlated with the time that had elapsed since the last time a woman had given birth. RA risk was lowest among women whose last birth occurred 1-5 years previously (RR 0.29), with risk reduction lessening progressively as the time since the last birth increased (for those 5-15 years since last birth, RR 0.51; for those >15 years, RR 0.76), compared with nulliparous women (P for trend = 0.007). No correlation was observed between RA risk and either age at the time a woman first gave birth or a woman's total number of births. Among cases with the highest genetic risk of RA (i.e., those with 2 copies of RA-associated HLA alleles), a significant underrepresentation of parous women versus nulliparous women was observed (P = 0.02). CONCLUSION: In the present study, there was a significantly lower risk of RA in parous women that was strongly correlated with the time elapsed since a woman had last given birth. While the explanation for our findings is not known, HLA-disparate fetal microchimerism can persist many years after a birth and could confer temporary protection against RA. PMID- 20309865 TI - Expression of Toll-like receptor 3 and Toll-like receptor 7 in muscle is characteristic of inflammatory myopathy and is differentially regulated by Th1 and Th17 cytokines. AB - OBJECTIVE: To assess the expression of Toll-like receptor 3 (TLR-3) and TLR-7 in muscle tissue from patients with polymyositis (PM) and dermatomyositis (DM) and to investigate the function and regulation of TLR-3 in cultured muscle cells. METHODS: The expression of TLR-3, TLR-7, HLA class I, and CD56, a marker of immature myoblast precursors, was analyzed using immunohistochemistry. TLR-3 regulation and signaling were assessed in myoblasts and in differentiated myotubes with the TLR-3 agonist poly(I-C), necrotic myoblasts, and Th1 and Th17 cytokines, in the presence or absence of neutralizing anti-TLR-3 antibody. Levels of TLR-3 messenger RNA (mRNA) were quantified by reverse transcription-polymerase chain reaction. Levels of interleukin-6 (IL-6), CCL20, and IL-8 were determined by enzyme-linked immunosorbent assay. RESULTS: TLR-3 and TLR-7 were expressed in PM/DM tissues, but not in noninflammatory muscle tissues, and were primarily detected in inflammatory infiltrates, although a few muscle cells were also positive. These TLR-3- and TLR-7-positive fibers expressed high levels of CD56 and HLA class I antigens. A synergy between poly(I-C) and IL-17 was observed for the production of IL-6 and CCL20. Similarly, stimulation with necrotic myoblasts increased IL-6 production, and stimulation with necrotic myoblasts in combination with IL-17 further increased the induction of IL-6. TLR-3 blockade decreased the inducing effect of necrotic myoblasts and IL-17 on IL-6 production. Stimulation with interferon-gamma (IFNgamma) increased TLR-3 mRNA levels, but IL-17 down regulated the inducing effect of IFNgamma. CONCLUSION: Our findings indicate that TLR-3 and TLR-7 are expressed in inflammatory myopathic tissues, particularly in immature myoblast precursors. Necrotic muscle cells activate cytokine production, in part, through the TLR-3 pathway, with a differential regulatory effect of Th1 and Th17 cytokines. PMID- 20309864 TI - The histopathologic associates of neurometabolite abnormalities in fatal neuropsychiatric systemic lupus erythematosus. AB - OBJECTIVE: To determine the histopathologic basis of altered brain neurometabolites in neuropsychiatric systemic lupus erythematosus (NPSLE). METHODS: Brain neurometabolite concentrations in a 20-voxel area of the brain were determined premortem by magnetic resonance spectroscopy (MRS) in 7 individuals with NPSLE. Absolute concentrations of neurometabolite for N acetylaspartate (NAA), choline, creatine, and lactate were measured. After the death of the patients, histopathologic changes were determined at autopsy of the brain and were matched voxel-by-voxel with the neurometabolites. RESULTS: The mean +/- SD absolute concentrations of NAA (9.15 +/- 1.78 mM in patients versus 12.2 +/- 0.8 mM in controls; P < 0.01) and creatine (6.43 +/- 0.16 mM in patients versus 6.90 +/- 0.60 mM in controls; P < 0.003) were significantly reduced and the concentration of choline (2.51 +/- 0.42 mM in patients versus 1.92 +/- 0.32 mM in controls; P < 0.04) was significantly elevated in NPSLE patients as compared with controls. Widespread heterogeneous changes in the histologic features of the brain were present, including microinfarcts, microhemorrhages, bland angiopathy, thrombotic angiopathy with platelet and fibrin thrombi, neuronal necrosis in various states of resolution, reduced numbers of axons and neurons, vacuole and space formation among the fibers, reduced numbers of oligodendrocytes, reactive microglia and astrocytes, lipid-laden macrophages, and cyst formation. Neurometabolite abnormalities were closely associated with underlying histopathologic changes in the brain: 1) elevated choline levels were independently associated with gliosis, vasculopathy, and edema (r = 0.75, P < 0.004 in the multivariate model); 2) reduced creatine levels with reduced neuronal-axonal density and gliosis (r = 0.72, P < 0.002 in the multivariate model); 3) reduced NAA levels with reduced neuronal-axonal density (r = 0.66, P < 0.001 in the multivariate model); and 4) the presence of lactate with necrosis, microhemorrhages, and edema (r = 0.996, P < 0.0001 in the multivariate model). CONCLUSION: Altered neurometabolites in NPSLE patients, as determined by MRS, are a grave prognostic sign, indicating serious underlying histologic brain injury. PMID- 20309866 TI - Near-infrared lymphatic imaging demonstrates the dynamics of lymph flow and lymphangiogenesis during the acute versus chronic phases of arthritis in mice. AB - OBJECTIVE: To develop an in vivo imaging method to assess lymphatic draining function in the K/BxN mouse model of inflammatory arthritis. METHODS: Indocyanine green, a near-infrared fluorescent dye, was injected intradermally into the footpads of wild-type mice, mouse limbs were illuminated with an 806-nm near infrared laser, and the movement of indocyanine green from the injection site to the draining popliteal lymph node (LN) was recorded with a CCD camera. Indocyanine green near-infrared images were analyzed to obtain 5 measures of lymphatic function across time. Images of K/BxN arthritic mice and control nonarthritic littermates were obtained at 1 month of age, when acute joint inflammation commenced, and again at 3 months of age, when joint inflammation became chronic. Lymphangiogenesis in popliteal LNs was assessed by immunochemistry. RESULTS: Indocyanine green and its transport within lymphatic vessels were readily visualized, and quantitative measures were derived. During the acute phase of arthritis, the lymphatic vessels were dilated, with increased indocyanine green signal intensity and lymphatic pulses, and popliteal LNs became fluorescent quickly. During the chronic phase, new lymphatic vessels were present near the foot. However, the appearance of indocyanine green in lymphatic vessels was delayed. The size and area of popliteal LN lymphatic sinuses progressively increased in the K/BxN mice. CONCLUSION: Our findings indicate that indocyanine green near-infrared lymphatic imaging is a valuable method for assessing the lymphatic draining function in mice with inflammatory arthritis. Indocyanine green-near-infrared imaging of K/BxN mice identified 2 distinct lymphatic phenotypes during the acute and chronic phase of inflammation. This technique can be used to assess new therapies for lymphatic disorders. PMID- 20309867 TI - Dihydrosphingosine 1-phosphate has a potent antifibrotic effect in scleroderma fibroblasts via normalization of phosphatase and tensin homolog levels. AB - OBJECTIVE: Previous studies have revealed a phosphatase and tensin homolog (PTEN) dependent interaction between the sphingolipid agonist dihydrosphingosine 1 phosphate (dhS1P) and the transforming growth factor beta/Smad3 signaling pathway. This study was undertaken to examine responses of systemic sclerosis (SSc) fibroblasts to sphingosine 1-phosphate (S1P) and dhS1P and to gain further insight into the regulation of the S1P/dhS1P/PTEN pathway in SSc fibrosis. METHODS: Fibroblast cultures were established from skin biopsy samples obtained from patients with SSc and matched healthy controls. Western blotting and quantitative polymerase chain reaction were used to measure protein and messenger RNA levels, respectively. PTEN protein was examined in skin biopsy samples by immunohistochemistry. RESULTS: PTEN protein levels were low in SSc fibroblasts and correlated with elevated levels of collagen and phospho-Smad3 and reduced levels of matrix metalloproteinase 1 (MMP-1). Treatment with dhS1P restored PTEN levels and normalized collagen and MMP-1 expression, as well as Smad3 phosphorylation status in SSc fibroblasts. S1P was strongly profibrotic in SSc and control fibroblasts. Distribution of S1P receptor isoforms was altered in SSc fibroblasts, which had reduced levels of S1P receptor 1 and S1P receptor 2 and elevated levels of S1P receptor 3. Only depletion of S1P receptor 1 abrogated the effects of dhS1P and S1P in control dermal fibroblasts. In contrast, depletion of either S1P receptor 1 or S1P receptor 2 prevented the effects of S1P and dhS1P in SSc fibroblasts. CONCLUSION: Our findings demonstrate that PTEN deficiency is a critical determinant of the profibrotic phenotype of SSc fibroblasts. The antifibrotic effect of dhS1P is mediated through normalization of PTEN expression, suggesting that dhS1P or its derivatives may be effective as therapeutic antifibrotic agents. The distribution and function of S1P receptors differ in SSc and healthy fibroblasts, suggesting that alteration in the sphingolipid signaling pathway may contribute to SSc fibrosis. PMID- 20309868 TI - Angiogenesis and the persistence of inflammation in a rat model of proliferative synovitis. AB - OBJECTIVE: To determine whether blood vessel growth at the onset of resolving synovitis leads to its subsequent persistence and whether inhibiting this angiogenesis at the onset of persistent inflammation leads to its subsequent resolution. METHODS: Inflammation and angiogenesis were induced by injection of 0.03% carrageenan and/or 6 pmoles of fibroblast growth factor 2 (FGF-2) into rat knees. A brief treatment with the angiogenesis inhibitor PPI-2458 (5 mg/kg orally on alternate days) was administered 1 day before and up to 3 days after synovitis induction. Controls comprised naive and vehicle-treated rats. Synovial angiogenesis was measured using the endothelial cell proliferation index, and inflammation was determined by measuring joint swelling and macrophage percentage area. Data are presented as the geometric mean (95% confidence interval). RESULTS: Intraarticular injection of 0.03% carrageenan into rat knees produced acute synovitis, which was not associated with synovial angiogenesis and which resolved within 29 days. Injection of FGF-2 (6 pmoles) induced synovial angiogenesis without significant synovitis. Stimulation of angiogenesis with FGF 2 at the time of carrageenan injection was followed by synovitis that persisted for 29 days. Persistence of carrageenan/FGF-2-induced synovitis was prevented by systemic administration of 3 doses of the angiogenesis inhibitor PPI-2458 during the acute phase. CONCLUSION: Our findings indicate that conversion of acute inflammation to chronic inflammation may be due to the stimulation of angiogenesis, and brief antiangiogenic treatment during the acute phase of synovitis may prevent its subsequent progression. Clinical studies will be needed to determine whether brief antiangiogenic treatment may reduce the burden of inflammatory joint diseases such as rheumatoid arthritis by facilitating the resolution of early synovitis. PMID- 20309869 TI - Tetracycline-regulated bone morphogenetic protein 2 gene expression in lentivirally transduced primary rabbit chondrocytes for treatment of cartilage defects. AB - OBJECTIVE: Treatment of cartilage defects is still challenging, primarily because of the poor self-healing capacity of articular cartilage. Gene therapy approaches have gained considerable attention, but, depending on the vector system used, they can lead to either limited or unrestrained gene expression, and therefore regulation of gene expression is necessary. This study was undertaken to construct an efficient tetracycline (Tet)-regulated, lentivirally mediated system for the expression of growth factor bone morphogenetic protein 2 (BMP-2) in primary rabbit chondrocytes that will allow for the induction and termination of growth factor gene expression once cartilage regeneration is complete. METHODS: Chondrogenic ATDC5 cells and primary rabbit chondrocytes were lentivirally transduced with different tetracycline-on (Tet-On)-regulated, self-inactivating vectors for the induction of expression of enhanced green fluorescent protein (eGFP) or BMP-2, using either a 1-vector system or a 2-vector system. RESULTS: Expression of eGFP was induced on ATDC5 cells and chondrocytes. The highest induction rate and highest level of gene expression were reached when the spleen focus-forming virus long terminal repeat promoter was used to drive the reverse transactivator expression, after the addition of doxycycline, in chondrocytes. An up to 20-fold induction of Tet-mediated BMP-2 expression was observed on ATDC5 cells. The extent of induction and expression level of BMP-2 in chondrocytes were similar between the 1-vector system- and 2-vector system-infected cells (mean +/- SD 15.5 +/- 1.1 ng/ml and 14.6 +/- 0.4 ng/ml, respectively). In addition, prolonged induction and switching-off of BMP-2 expression, as well as repeated induction, were demonstrated. Production of proteoglycans, as shown by Alcian blue staining, demonstrated the functionality of the lentivirally expressed BMP-2 under induced conditions. CONCLUSION: The lentivirally mediated Tet-On system is an effective strategy for efficient, repeatedly inducible expression of BMP-2 in primary rabbit chondrocytes. Therefore, use of this system in in vivo experiments may be a promising approach as a treatment strategy for cartilage defects. PMID- 20309870 TI - Heparanase in primary human osteoblasts. AB - Heparanase (HPSE) is known to be involved in fracture repair in mice, but its presence and function in human bone formation remains unclear. Our aim was to determine the expression of HPSE in human bone forming osteoblasts and to better understand its role in osteogenesis. HPSE protein expression and enzymatic activity were demonstrated in osteoblasts isolated from trabecular bone specimens of patients with osteoporosis (OP) and from healthy subjects, although the levels differed markedly. Thus, low levels of HPSE expression were observed in osteoporotic osteoblasts, including in the nucleus compared to those from healthy subjects. Notably, HPSE gene expression was associated with alkaline phosphatase (ALP) activity, the bone turnover marker. Gene profile studies demonstrated that osteogenic genes were downregulated in osteoporotic osteoblasts. We further exposed osteoblasts to exogenous HPSE and found that the level of histone H3 phosphorylation was increased. We provide evidence, for the first time, demonstrating that HPSE expresses and functions in human osteoblasts. Our data suggest that previously undescribed function of HPSE-mediated osteoblastogenesis through regulation of osteogenic gene expression and histone H3 modification. HPSE upregulation may be a novel therapeutic approach in the prevention and treatment of OP. PMID- 20309871 TI - High-resolution NMR correlation experiments in a single measurement (HR-PANACEA). AB - Three important NMR pulse sequences, INADEQUATE, HSQC and three-dimensional HMBC have been combined into a single entity called high-resolution Parallel Acquisition NMR: an All-in-one Combination of Experimental Applications (HR PANACEA) to provide reliable structural information about a small molecule in a single measurement. This exploits a recent instrumental development that permits simultaneous acquisition of signals from several nuclear species, using multiple receivers. Where high-precision values of the long-range heteronuclear splittings are important, selected regions of a large experimental data matrix are extracted and examined with the highest possible resolution. The J-doubling technique is then applied to derive precise values for these couplings. As proof of principle, the method is applied to the molecule of methyl salicylate, confirming the expected conformation of the C-O-H moiety. PMID- 20309872 TI - Synthesis and in-vitro cytotoxicity of poly-functionalized 4-(2-arylthiazol-4-yl) 4H-chromenes. AB - A new series of 4-aryl-4H-chromenes bearing a 2-arylthiazol-4-yl moiety at the 4 position were prepared as potential cytotoxic agents. The in-vitro cytotoxic activity of the synthesized 4-aryl-4H-chromenes was investigated in comparison with etoposide, a well-known anticancer drug, using MTT colorimetric assay. Among them, the 2-(2-chlorophenyl)thiazol-4-yl analog 4b showed the most potent activity against nasopharyngeal epidermoid carcinoma KB, medulloblastoma DAOY, and astrocytoma 1321N1, and compound 4d bearing a 2-(4-chlorophenyl)thiazol-4-yl moiety at the 4-position of the chromene ring exhibited the best inhibitory activity against breast cancer cells MCF-7, lung cancer cells A549, and colon adenocarcinoma cells SW480 with IC(50 )values less than 5 microM. The ability of compound 4b to induce apoptosis was confirmed in a nuclear morphological assay by DAPI staining in the KB and MCF-7 cells. PMID- 20309873 TI - Synthesis and antineoplastic activity of O-alkylated derivatives of 7 hydroximinoandrost-5-ene steroids. AB - Varied positioning of the hydroximino group on the parental steroid skeleton results in remarkable changes in the antineoplastic activity profile of the compounds. Here, the compound 7-oximino-5-androstene and its O-alkylated derivatives have been prepared and screened for cytotoxic and aromatase inhibitory activity. The steroidal 7-oximino ether derivatives exhibited insignificant cytotoxic effects when screened against three cancer cell lines, MCF-7 (breast), NCl-H460 (lung), and SF-268 (CNS) at 100 microM. However, the imidazolyl-substituted steroidal oxime ethers displayed moderate inhibition of cytochrome P450 aromatase. PMID- 20309875 TI - GABA and glutamate immunoreactivity in tentacles of the sea anemone Phymactis papillosa (LESSON 1830). AB - Sea anemones have a structurally simple nervous system that controls behaviors like feeding, locomotion, aggression, and defense. Specific chemical and tactile stimuli are transduced by ectodermal sensory cells and transmitted via a neural network to cnidocytes and epithelio-muscular cells, but the nature of the neurotransmitters operating in these processes is still under discussion. Previous studies demonstrated an important role of peptidergic transmission in cnidarians, but during the last decade the contribution of conventional neurotransmitters became increasingly evident. Here, we used immunohistochemistry on light and electron microscopical preparations to investigate the localization of glutamate and GABA in tentacle cross-sections of the sea anemone Phymactis papillosa. Our results demonstrate strong glutamate immunoreactivity in the nerve plexus, while GABA labeling was most prominent in the underlying epithelio muscular layer. Immunoreactivity for both molecules was also found in glandular epithelial cells, and putative sensory cells were GABA positive. Under electron microscopy, both glutamate and GABA immunogold labeling was found in putative neural processes within the neural plexus. These data support a function of glutamate and GABA as signaling molecules in the nervous system of sea anemones. PMID- 20309876 TI - Stratification and synaptogenesis in the mushroom body of the honeybee, Apis mellifera. AB - Stratification is a basic anatomical feature of central brain in both vertebrates and many invertebrates. The aim of this study was to investigate the relationship between stratification and synaptogenesis in the developing mushroom bodies of the honeybee. During metamorphosis, the vertical lobe of mushroom body shows progressive stratification with three thick primary strata and more secondary strata and laminae. Three primary strata are formed at the metamorphic stage P1, before the youngest generation of the mushroom body intrinsic neurons, Kenyon cells, is produced. Thus, the primary strata within the lobe are unlikely to represent three major subpopulations of the Kenyon cells sequentially produced in the mushroom bodies. Formation of laminae starts at the stage P2 and culminates at the end of metamorphosis. The laminae appear within the lobe rather than being added sequentially from the ingrowth stratum. Alternating dark and light lamina (lamina doublets) are formed in the vertical lobe in late metamorphosis (stages P6-P9), but they are not visible in adults. The pattern of stratification is not continuous along the vertical lobe at the same developmental stage, and resorting of axons of the Kenyon cells is likely to occur within dark laminae. In the developing vertical lobe, dark laminae show lower synaptic density and exhibit an ultra structure that is indicative for a delay in synaptogenesis relative to the primary strata. A local transient block of synaptogenesis within the dark laminae may provide correct targeting of Kenyon cells by extrinsic mushroom body neurons. PMID- 20309874 TI - Rheumatoid arthritis risk allele PTPRC is also associated with response to anti tumor necrosis factor alpha therapy. AB - OBJECTIVE: Anti-tumor necrosis factor alpha (anti-TNF) therapy is a mainstay of treatment in rheumatoid arthritis (RA). The aim of the present study was to test established RA genetic risk factors to determine whether the same alleles also influence the response to anti-TNF therapy. METHODS: A total of 1,283 RA patients receiving etanercept, infliximab, or adalimumab therapy were studied from among an international collaborative consortium of 9 different RA cohorts. The primary end point compared RA patients with a good treatment response according to the European League Against Rheumatism (EULAR) response criteria (n = 505) with RA patients considered to be nonresponders (n = 316). The secondary end point was the change from baseline in the level of disease activity according to the Disease Activity Score in 28 joints (triangle upDAS28). Clinical factors such as age, sex, and concomitant medications were tested as possible correlates of treatment response. Thirty-one single-nucleotide polymorphisms (SNPs) associated with the risk of RA were genotyped and tested for any association with treatment response, using univariate and multivariate logistic regression models. RESULTS: Of the 31 RA-associated risk alleles, a SNP at the PTPRC (also known as CD45) gene locus (rs10919563) was associated with the primary end point, a EULAR good response versus no response (odds ratio [OR] 0.55, P = 0.0001 in the multivariate model). Similar results were obtained using the secondary end point, the triangle upDAS28 (P = 0.0002). There was suggestive evidence of a stronger association in autoantibody-positive patients with RA (OR 0.55, 95% confidence interval [95% CI] 0.39-0.76) as compared with autoantibody-negative patients (OR 0.90, 95% CI 0.41 1.99). CONCLUSION: Statistically significant associations were observed between the response to anti-TNF therapy and an RA risk allele at the PTPRC gene locus. Additional studies will be required to replicate this finding in additional patient collections. PMID- 20309879 TI - Prospective identification of tumorigenic osteosarcoma cancer stem cells in OS99 1 cells based on high aldehyde dehydrogenase activity. AB - High aldehyde dehydrogenase (ALDH) activity has recently been used to identify tumorigenic cell fractions in many cancer types. Herein we hypothesized that a subpopulation of cells with cancer stem cells (CSCs) properties could be identified in established human osteosarcoma cell lines based on high ALDH activity. We previously showed that a subpopulation of cells with high ALDH activity were present in 4 selected human osteosarcoma cell lines, of which a significantly higher ALDH activity was present in the OS99-1 cell line that was originally derived from a highly aggressive primary human osteosarcoma. Using a xenograft model in which OS99-1 cells were grown in NOD/SCID mice, we identified a highly tumorigenic subpopulation of osteosarcoma cells based on their high ALDH activity. Cells with high ALDH activity (ALDH(br) cells) from the OS99-1 xenografts were much less frequent, averaging 3% of the entire tumor population, compared to those isolated directly from the OS99-1 cell line. ALDH(br) cells from the xenograft were enriched with greater tumorigenicity compared to their counterparts with low ALDH activity (ALDH(lo) cells), generating new tumors with as few as 100 cells in vivo. The highly tumorigenic ALDH(br) cells illustrated the stem cell characteristics of self-renewal, the ability to produce differentiated progeny and increased expression of stem cell marker genes OCT3/4A, Nanog and Sox-2. The isolation of osteosarcoma CSCs by their high ALDH activity may provide new insight into the study of osteosarcoma-initiating cells and may potentially have therapeutic implications for human osteosarcoma. PMID- 20309880 TI - Prognostic significance of differentially expressed miRNAs in esophageal cancer. AB - Altered microRNA (miRNA) expression has been found to promote carcinogenesis, but little is known about the role of miRNAs in esophageal cancer. In this study, we selected 10 miRNAs and analyzed their expression in 10 esophageal cancer cell lines and 158 tissue specimens using Northern blotting and in situ hybridization, respectively. We found that Let-7g, miR-21 and miR-195p were expressed in all 10 cell lines, miR-9 and miR-20a were not expressed in any of the cell lines, and miR-16-2, miR-30e, miR-34a, miR-126 and miR-200a were expressed in some of the cell lines but not others. In addition, transient transfection of miR-34a inhibited c-Met and cyclin D1 expression and esophageal cancer cell proliferation, whereas miR-16-2 suppressed RAR-beta(2) expression and increased tumor cell proliferation. Furthermore, we found that miR-126 expression was associated with tumor cell dedifferentiation and lymph node metastasis, miR-16-2 was associated with lymph node metastasis, and miR-195p was associated with higher pathologic disease stages in patients with esophageal adenocarcinoma. Kaplan-Meier analysis showed that miR-16-2 expression and miR-30e expression were associated with shorter overall and disease-free survival in all esophageal cancer patients. In addition, miR-16-2, miR-30e and miR-200a expression were associated with shorter overall and disease-free survival in patients with esophageal adenocarcinoma; however, miR-16-2, miR-30e and miR-200a expression were not associated with overall or disease-free survival in squamous cell carcinoma patients. Our data indicate that further evaluation of miR-30e and miR 16-2 as prognostic biomarkers is warranted in patients with esophageal adenocarcinoma. In addition, the role of miR-34a in esophageal cancer also warrants further study. PMID- 20309881 TI - Loss of MKK4 expression in ovarian cancer: a potential role for the epithelial to mesenchymal transition. AB - In the current study, we investigated the mechanism relating downregulation of mitogen-activated protein kinase kinase 4 (MKK4) expression to development of ovarian cancer. Over-expression of the MKK4 gene in TOV-21 G cells, a line with homozygous deletion of MKK4, resulted in morphologic changes in which cells growing in a scattered, fibroblast-like pattern formed tightly packed colonies. Based on a wound healing assay and a Matrigel invasion assay, we determined that both motility and invasiveness of MKK4-transfected TOV-21G cells were significantly reduced compared to control vector-transfected cells. To confirm that MKK4 expression related to tumor invasion resulted from an epithelial to mesenchymal transition (EMT)-like morphological change, we used 2 independent but complementary approaches. MKK4 gene knockdown in MDAH 2774 cells over-expressing MKK4 increased invasion activity. Additionally, engineered expression of MKK4 in SKOV3 cells, a line with low endogenous MKK4 expression, produced a phenotype similar to that of TOVG-21G. Interestingly, we found that MKK4 upregulation caused downregulation of phosphorylated NF-kappaB and Twist, as well as upregulation of E-cadherin, in TOVG-21G and SKOV3 cells. Reciprocal results were obtained in MDAH 2774 cells with MKK4 knockdown. Our results suggest that MKK4 downregulation causes increased phosphorylation NF-kappaB. This promotes Twist over-expression, resulting in E-cadherin downregulation that induces EMT in ovarian cancer. PMID- 20309882 TI - Effect of inbreeding depression on growth and fluctuating asymmetry in Turkish young males. AB - This study sought to examine the effects of inbreeding on physical development and fluctuating asymmetry (FA). A total 144 male high-school students (mean age = 18.11 +/- 0.52) whose parents are first cousins (F = 0.125) of low-socioeconomic status and 146 male students (mean age = 18.08 +/- 0.54) from the same school who do not have any consanguineous parents (F = 0) were observed in Ankara. In addition to the weight and height measurements of the individuals, eight bilateral traits (hand width, elbow width, wrist width, knee width, ankle width, foot width, ear length, and ear width) were measured. Whereas the inbred group has lower values in terms of weight and height, the difference in body mass index between the groups is not significant. Although the inbred group is more asymmetric in terms of the observed bilateral traits, the differences are below the significance level. However, the composite FA index shows that the inbred group is more asymmetric and the difference is significant (P < 0.05). Inbreeding depression has a negative effect on weight and height development, and a negative effect on developmental stability. PMID- 20309883 TI - Toward quantifying the usage costs of human immunity: Altered metabolic rates and hormone levels during acute immune activation in men. AB - There is a paucity of data on the energetic demands of human immune functions, despite the fact that both clinical medicine and evolutionary biology would benefit from further clarification of these costs. To better understand the energetic requirements of mounting a mild immune response, as well as some of the major hormonal changes underlying these metabolic changes, we examined changes in resting metabolic rate (RMR) and hormones during and after respiratory tract infection in young adult men. An epidemiologic passive detection design was used to recruit 25 nonfebrile subjects naturally infected with respiratory tract pathogens. Symptomology, percent body fat, RMR, salivary testosterone and cortisol, and other information were collected at a minimum of three time points during and after convalescence. Comparisons of the differences in RMR, testosterone, and cortisol between sampling days within individual cases were made using paired t-tests. Participants experienced 8% higher RMR during illness, and a subset of these men experienced a mean increase greater than 14%. The participants also experienced 10% lower testosterone levels during illness, and a subset of these participants experienced a mean decrease of 30%, although cortisol levels did not change significantly. These results document elevated RMR following natural pathogen exposure in adult humans, demonstrating that even mild immune reactions can elicit significant increases in energy expenditure. Understanding the costs of immunity and the immunomodulatory actions of hormones are central to understanding the role of immunity in human life history evolution. PMID- 20309888 TI - Technology of creation of an expert system for diagnosing thyroid pathology based on a set of qualitative signs of cell atypia. AB - An expert system for differential diagnosis of thyroid pathology has been developed, in which the function of transforming qualitative signs of cell atypia into the quantitative form is realized. It based on the set of qualitative signs of cell atypia and works in the mode by the question-answer principle. An expert system (software) contained the X-matrix and six standard S-matrices. The X matrix was designed for filling with the alternative answers yes/no regarding the presence of cells with characteristic signs of atypia in the visual fields of a preparation. S-matrices characterized the main forms of thyroid diseases, such as papillary and follicular cancer, follicular adenoma, autoimmune thyroiditis, nodular colloid and diffuse toxic goiter, by their set of yes/no answers. The answers entered to the X-matrix were compared with answers of the S-matrix. Each element of each S-matrix, besides the answers yes/no, contained its weighting coefficient corresponding to a qualitative feature of a certain nosologic form. Weighting coefficient of each feature for every nosologic form was calculated by their frequency of occurrence in 30 visual fields. Comparison of X-matrices with S-matrices and verification of diagnosis according to the value of a diagnostic index with a percentage probability was performed in the automatic mode. Diagnostic index was determined by the sum of weighting coefficients of features with the coincident yes/no answers, while comparing X-matrix elements with the corresponding S-matrix elements. The software displayed on the monitor is the list of nosologic forms in the order of decreasing the diagnostic index values. PMID- 20309889 TI - Profiling of mouse synaptosome proteome and phosphoproteome by IEF. AB - Synapses play important roles in neurotransmission and neuroplasticity. For an in depth analysis of the synaptic proteome and phosphoproteome, synaptosomal proteins from whole mouse brain were analyzed by IEF and MS resulting in the largest synaptosome proteome described to date, with 2980 unique proteins identified with two or more peptides. At the same time, 118 synaptosomal phosphoproteins were identified, eight of which are reported for the first time as phosphorylated. Expression of selected proteins in synaptosomes was investigated by Western blot. We demonstrate that IEF is a powerful method to interrogate complex samples such as brain tissue both at the proteome and the phosphoproteome level without the need of additional enrichment for phosphoproteins. The detailed synaptoproteome data set reported here will help to elucidate the molecular complexity of the synapse and contribute to our understanding of synaptic systems biology in health and disease. PMID- 20309890 TI - Simultaneous electrophoretic analysis of proteins of very high and low molecular mass using Tris-acetate polyacrylamide gels. AB - To separate and analyze giant and small proteins in the same electrophoresis gel, we have used a 3-15% polyacrylamide gradient gel containing 2.6% of the crosslinker bisacrylamide and 0.2 M of Tris-acetate buffer (pH 7.0). Samples were prepared in a sample buffer containing lithium dodecyl sulphate and were run in the gel described above using Tris-Tricine-SDS-sodium bisulfite buffer, pH 8.2, as electrophoresis buffer. Here, we show that this system can be successfully used for general applications of SDS-PAGE such as CBB staining and immunoblot. Thus, by using Tris-acetate 3-15% polyacrylamide gels, it is possible to simultaneously analyze proteins, in the mass range of 10-500 kDa, such as HERC1 (532 kDa), HERC2 (528 kDa), mTOR (289 kDa), Clathrin heavy chain (192 kDa), RSK (90 kDa), S6K (70 kDa), beta-actin (42 kDa), Ran (24 kDa) and LC3 (18 kDa). This system is highly sensitive since it allows detection from as low as 10 microg of total protein per lane. Moreover, it has a good resolution, low cost, high reproducibility and allows for analysis of proteins in a wide range of weights within a short period of time. All these features together with the use of a standard electrophoresis apparatus make the Tris-acetate-PAGE system a very helpful tool for protein analysis. PMID- 20309891 TI - Proteomic analysis reveals changes in the hippocampus protein pattern of rats exposed to dietary zinc deficiency. AB - An experiment was performed to observe protein changes in the hippocampus of zinc deficient (ZD) rats. Twenty-four male weanling Wistar rats were randomly assigned to ZD (n=12) and control groups (n=12). After 4-wk treatment, we used 2-DE and MALDI-TOF-MS to analyze the proteomes of hippocampus in the two groups. One of the important differential proteins, ubiquitin C-terminal hydrolase L1 (Uch-L1), was confirmed by Western blot assays. The results demonstrated that compared with the controls, ZD rats had significantly reduced plasma zinc concentration and alkaline phosphatase activity. The latency period in passive avoidance performance was also significantly shorter for the ZD rats. Nine proteins were differentially expressed between the two groups. Eight of them were identified. Tubulin beta chain and voltage-dependent anion channel 1 were upregulated, while mitochondrial aldehyde dehydrogenase, alpha-enolase, dimethylarginine dimethylaminohydrolase 1, F-actin capping protein alpha-2 subunit, pyruvate dehydrogenase beta and Uch-L1 were downregulated, respectively. Importantly, some of the identified proteins (e.g. Uch-L1) are known to be involved in cognitive impairment. Western blot analysis of hippocampus Uch-L1 expression confirmed the proteomic findings. The data indicated that there may be common mechanisms or pathways in cognitive dysfunction between neurodegenerative diseases and zinc deficiency. PMID- 20309892 TI - Improved sample preparation method for glycan analysis of glycoproteins by CE-LIF and CE-MS. AB - CE is a high-resolution separation technique broadly used in the biotechnology industry for carbohydrate analysis. The standard sample preparation protocol for CE analysis of glycans released from glycoproteins generally requires derivatization times of overnight at 37 degrees C, using > or =100 fold excess of fluorophore reagent, 8-aminopyrene-1,3,6-trisulfonic-acid, if the sample is unknown, or it is a regulated biotherapeutic product, possibly containing terminal sialic acid(s). In this paper, we report on significant improvements for the standard CE sample preparation method of glycan analysis. By replacing the conventionally used acetic acid catalyst with citric acid, as low as 1:10 glycan to fluorophore molar ratio (versus the typical 1:> or =100 ratio) maintained the >95% derivatization yield at 55 degrees C with only 50 min reaction time. Terminal sialic acid loss was negligible at 55 degrees C during the derivatization process, and indicating that the kinetics of labeling at 55 degrees C was faster than the loss of sialic acid from the glycan. The reduced relative level of 8-aminopyrene-1,3,6-trisulfonic-acid simplified the removal of excess reagent, important in both CE-LIF (electrokinetic injection bias) and CE MS (ion suppression). Coupling CE- ESI-MS confirmed that the individual peaks separated by CE corresponded to single glycans and increased the confidence of structural assignment based on glucose unit values. PMID- 20309893 TI - Endogenous morphine levels after laparoscopic versus open colectomy. AB - BACKGROUND: Endogenous morphine may be a component of the acute-phase response to surgical trauma that affects both hospital stay and gastrointestinal motility. The purpose of this study was to assess the responses of endogenous morphine, stress hormones and cytokines following laparoscopic and open colectomy. METHODS: Twenty patients who underwent a laparoscopic colectomy were compared with ten who had an open procedure. Data collected included operative blood loss, operating time and time to pass flatus. Plasma endogenous morphine was measured before and immediately after operation, and 3, 24 and 48 h later. RESULTS: Age was comparable in the two groups. Operating time (mean 92.2 versus 61.3 min), time to tolerance of solid food (56.8 versus 103.6 h) and hospital stay (median 4 versus 6 days) were all significantly longer in the open group. Endogenous morphine levels rose immediately after open colectomy only and were higher than those after laparoscopic colectomy (8.69 versus 1.97 ng/ml; P < 0.001). Levels remained significantly higher than [corrected] in the laparoscopic group at 3 h (10.36 versus 0.52 ng/ml; P < 0.001) and 24 h, but were similar in both groups after 48 h. CONCLUSION: There is a greater degree of morphine synthesis after open than laparoscopic colectomy. PMID- 20309894 TI - Bariatric surgery reduces mortality in Swedish men. AB - BACKGROUND: Mortality is lower in obese patients who have undergone surgery for obesity than in those who have not. The majority of patients in these studies have been women. Perioperative mortality is known to be higher among men, and this may counterbalance the survival advantage seen after surgery. This cohort study compared mortality among operated obese patients, non-operated obese patients and a general control cohort of men. METHODS: The study was based on record linkage between Swedish registries. An operated obese, a non-operated obese and a general control cohort were created. The two non-operated cohorts were assigned pseudosurgery dates. Data regarding preoperative and postoperative morbidity were collected, as well as mortality data. RESULTS: Hazard ratios were calculated for mortality between the cohorts adjusting for preoperative morbidity and age. Comparison of all-cause mortality for the obese surgical and non surgical cohorts gave an adjusted mortality risk of 0.7 (95 per cent confidence interval (c.i.) 0.5 to 1.0) (P = 0.039); the adjusted mortality risk was 1.5 (95 per cent c.i. 1.1 to 2.0) (P = 0.011) when the obese surgical cohort was compared with the general control cohort. CONCLUSION: Bariatric surgery reduces overall mortality in obese men. PMID- 20309895 TI - Self-expanding metal stents as an alternative to surgical bypass for malignant gastric outlet obstruction. AB - BACKGROUND: Gastroduodenal obstruction due to malignancy can be difficult to palliate. Self-expanding metal stents (SEMS) are gaining acceptance as an effective alternative to surgical bypass. METHODS: Patients not suitable for surgical bypass, with complete gastric outlet obstruction as a result of malignancy, were offered palliation with SEMS from November 2004 to December 2008. The procedure was performed under fluoroscopic guidance and conscious sedation. Data were collected prospectively. RESULTS: Seventy patients underwent SEMS placement (hepatobiliary and pancreatic malignancy, 44; antral gastric carcinoma, 19; other, seven). Follow-up was complete in 69 patients (99 per cent). Technical and clinical success rates were 93 and 95 per cent respectively. Median hospital stay was 2 (range 1-18) days, median survival was 1.8 (0.1-19.0) months, and 87 per cent had improved intake after SEMS placement, as determined by Gastric Outlet Obstruction Severity Score before and after stenting (P < 0.001). Complications included two episodes of minor bleeding. CONCLUSION: The use of SEMS to alleviate complete malignant gastric outlet obstruction in patients with limited life expectancy is successful in re-establishing enteral intake in most patients, with minimal morbidity, no mortality and a short hospital stay. PMID- 20309896 TI - Use of different buffers for detection and separation in determination of physio active components in oolong tea infusion by CZE with amperometric detection. AB - With a view of simultaneous determination of physio-active ingredients in oolong tea infusion: sugars, amino acids, epigallocatechin gallate and ascorbic acid, a novel CZE with amperometric detection method was studied. Operated in a wall-jet configuration, 100 mmol/L NaOH was used in detecting cell to lead the electrocatalysis oxidation behaviors of the analytes on a 300 mum diameter copper disc electrode (working electrode), while in separating capillary, a mild alkaline running buffer consisting in a mixture of 30 mmol/L borate and 40 mmol/L phosphates charged and carried analytes to detecting end. The methodology research was performed for system stability and suitability. Under the optimal CE conditions, analytes could be separated within moderate time period. Good linearity between peak area and concentration existed over three orders of magnitude; lower RSD and LOD were achieved. The oolong tea infusion was assayed and result was satisfactory. PMID- 20309897 TI - Optimum extraction process of polyphenols from Bridelia grandis stem bark using experimental design. AB - Euphorbiaceae barks are known to contain an appreciable amount of polyphenolic compounds responsible for several biological activities. Preliminary extraction from Bridelia grandis stem bark afforded high content of polyphenols, determined by spectrophotometric methods such as Folin-Ciocalteu (for total phenols, TP) and n-butanol-HCl (for condensed tannins, CT). A preliminary Plackett-Burman screening design was used to identify the key factors that influence the TP and CT extraction. Between all the variables known to influence the extraction from vegetable matrixes, six were selected; maceration was chosen as traditional extraction methodology. To investigate the effect of solvents and extraction method, methanol, acetone 70% (v/v in water), centrifugation and ultrasound were chosen. A full factorial design 2(3) was applied to optimize the extraction procedure. The responses were obtained analyzing the extracts for their TP and CT contents determined by the above-mentioned spectrophotometric methods. The results confirm that, within the explored domain, the optimum solvent is methanol and the optimum method is one-cycle centrifugation. Finally, it was also compared with the effect of maceration on the considered responses. It has never given results better than centrifugation, whereas in the case of CT it represents an advantage to employ a three-cycle centrifugation instead of one. PMID- 20309898 TI - Ionic liquid as extraction agent for detection of volatile phenols in wastewater and its regeneration. AB - Volatile phenols in the wastewater provide a basic parameter of the pollution. Spectrophotometric method based on the reactions of the individual phenols with 4 aminoantipyrine in the presence of an oxidizing agent is the current official analytical method in many countries. In this paper, we propose a method for extracting the resultant colored dye with ionic liquid 1-butyl-3 methylimidazolium hexafluorophosphate instead of chloroform. The results revealed excellent extraction efficiency, and the used ionic liquid could be regenerated easily. The method with small volume green reagent could be potentially applied in portable devices for in situ environmental analysis. PMID- 20309899 TI - A discussion on the process of defining 2-D separation selectivity. AB - In this manuscript, we investigate the importance that must be placed on the selection of standard compounds when undertaking studies to optimize the performance of 2-D-HPLC separations. A geometric approach to factor analysis and a measure of peak density across the separation space were applied to assess localized measures of component distributions within the 2-D separation plane. The results of this analysis of data showed that the measure of separation quality varied markedly, depending on the elution zone for which the test was undertaken. The study concluded that if standards cannot be obtained that adequately describe the entire sample matrix, the sample itself should be used, and also, the separation should be optimized for regions of interest, not necessarily the separation as a whole. PMID- 20309900 TI - Application of turbulent flow chromatography to the metabonomic analysis of human plasma: comparison with protein precipitation. AB - The use of turbulent flow chromatography (TFC) as a method for the rapid metabonomic LC-MS analysis of plasma as an alternative to solvent-based protein precipitation has been investigated. This comparison has shown that TFC can be effectively used in this application with the benefit that off-line sample handling is significantly reduced. However, analysis of the data obtained via TFC for human plasma reveals substantial differences in the overall metabolite profiles compared with methanol-precipitated HPLC-MS. This seems in part at least to be related to greatly reduced amounts of phospholipids (ca. 10 fold reduction) for the turbulent flow methodology compared with protein-precipitated samples. The significance of these differences with respect to metabolite profiles as a result of the sample preparation method used are discussed. PMID- 20309901 TI - Comprehensive 2-D chromatography of random and block methacrylate copolymers. AB - A comprehensive 2-D separation method was developed for the characterization of methacrylate copolymers. In both dimensions conditions were employed that give a critical separation for the homopolymer of one of the monomers in the copolymer, and exclusion behaviour for the other. The 2-D separation was realized by using a normal-phase column in one dimension and a reversed phase column in the other, and by precisely tuning the compositions of the two mobile phases employed. In the normal-phase dimension mixtures of THF and n-hexane or n-heptane were used as mobile phase, and in the reversed-phase dimension mixtures of ACN and THF. Moreover, stationary phase particles had to be selected for both columns that gave an exclusion window appropriate for the molecular size of the sample polymers to be characterized. The 2-D critical chromatography principle was tested with a polystyrene (PS)-polymethylmethacrylate (PMMA) block copolymer and with block and random polybutylmethacrylate (PBMA)-PMMA copolymers. Ideally, the retention time for a copolymer in both dimensions of this system would depend on the size of only one of the blocks, or on the contribution of only one of the monomers to the size of a random copolymer. However, it was found that the elution of the PS-PMMA block copolymer depended on the size of both blocks, even when the corresponding homopolymer of one of the monomers showed critical elution behaviour. Therefore, the method could not be calibrated for block sizes by using homopolymer standards alone. Still, it was shown that the method can be used to determine differences between samples (PS-PMMA and PBMA-PMMA) with respect to total molecular size or block sizes separately, or to average size and chemical composition for random copolymers. Block and random PBMA-PMMA copolymers showed a distinctly different pattern in the 2-D plots obtained with 2-D critical chromatography. This difference was shown to be related to the different procedures followed in the polymerization process, and the different molecular distributions resulting from these. PMID- 20309902 TI - Response surface optimization of ultrasound-assisted flavonoids extraction from the flower of Citrus aurantium L. var. amara Engl. AB - Citrus aurantium L. var. amara Engl is a member of genus Citrus (Rutaceae) and has been used in Chinese medicine with the effectiveness of digestant and expectorant. Ultrasonic-assisted extraction process for maximum flavonoids from the flower of Citrus aurantium L. var. amara Engl was investigated by response surface methodology. Through single factor experiment, ranges of the main variables (including ethanol concentration, solid/liquid ratio, extraction time and temperature) affecting the extraction yield of flavonoids were confirmed. Box Behnken central composite design consisting of 24 experimental runs and 5 replicates at zero point was then applied and a regress model was obtained to predict the optimal extraction yield. The ANOVA indicated that the regression equation fits very well with the actual situation, reflecting the relationship between the extraction yield of flavonoids and extraction conditions. The optimal conditions were as follows: extraction temperature 72.11 degrees C, time 51.89 min, ethanol concentration 51.19% and liquid/solid ratio of 40:10. Under the optimal conditions, the maximum response value of yield (1.88%) was consistent with the experimental value (1.87%), indicating the feasibility and validation of response surface methodology in optimizing the extraction of flavonoids from the flower of Citrus aurantium L. var. amara Engl. PMID- 20309903 TI - Urinary metabonomic study of lung cancer by a fully automatic hyphenated hydrophilic interaction/RPLC-MS system. AB - Lung cancer is one of the most common and lethal cancers in the world. In this study, a home-devised hydrophilic interaction chromatography/RPLC-MS (HILIC/RPLC MS) system was developed to study the urinary metabonomics of lung cancer patients. This system combined the orthogonal selectivity of HILIC and RPLC and could chromatographically reveal more comprehensive information of the urinary metabolites. Within a total analysis time of 50 min, we detected 577 polar metabolite ions on the first HILIC column and 261 apolar ones on the second RPLC column. In addition, an orthogonal signal correction partial least-squares discriminant analysis model was constructed to characterize differences between health and lung cancer cases. Eleven potential biomarkers, ten from HILIC column and one from the second RP column, were identified and all of these biomarkers were found upregulated in lung cancer patients. Overall, the results indicated that the developed HILIC/RPLC-MS system is a promising tool for metabonomic studies in revealing more information of highly complex samples. PMID- 20309904 TI - Comparison of various second-dimension gradient types in comprehensive two dimensional liquid chromatography. AB - Gradient elution provides significant improvement in peak capacity with respect to isocratic conditions. In the second dimension, gradients are limited to a short-time period available for separation. Various types of second-dimension gradients in comprehensive LC x LC are compared: (i) "full in fraction", (ii) "segment in fraction" and (iii) "continuously shifting" gradients, applied in orthogonal LC x LC separations of phenolic acids and flavones on a polyethylene glycol column in the first dimension and two types of porous shell fused-core C18 columns in the second dimension (Ascentis Express and Kinetex). The porous shell columns provide narrow bandwidths and fast second-dimension separations at moderate operating pressure that allows important savings of the overall separation time in comprehensive LC x LC separations. The effects of the gradient type on the bandwidths, theoretical peak capacity, separation time and column pressure in the second dimension were investigated. The type of gradient program controls the range of lipophilicity of sample compounds that can be separated in the second-dimension reversed-phase time period. This range can be calibrated using alkylbenzene standards, to design the separation conditions for complete sample separation, avoiding harmful wrap around of non-eluted compounds to the subsequent second-dimension fractions. PMID- 20309905 TI - Hydrophobic interaction membrane chromatography for plasmid DNA purification: Design and optimization. AB - Chromatography is one of the key operations in the downstream processing of plasmid DNA (pDNA). However, the increased demand for highly purified pDNA experienced in recent years has made clear the need for alternative processes capable of retaining the advantages of conventional chromatography, such as selectivity, while providing increased throughput at a lower cost. The work presented in this article outlines the development and optimization of an alternative hydrophobic interaction membrane chromatography process for the purification of pDNA. The studies included the modification of functionalized membrane supports with a linear alkyl chain ligand and the testing of chromatographic performance of these membranes. Three modification procedures were tested and the membranes were screened for their capacity and selectivity. The modified membranes could separate the model plasmid pVAX1-LacZ (6050 bp) from impurities in clarified Escherichia coli cell lysates (specifically RNA), with good resolution. Subsequent optimization of elution profiles with the best performing modified membrane, resulted in a high purification factor of 4.7, competitive with its bead process counterpart, and a plasmid yield of 73%. PMID- 20309906 TI - Unexpected roles for DEAD-box protein 3 in viral RNA sensing pathways. AB - Detection of viral nucleic acid within infected cells is essential to an effective anti-viral response. The retinoic acid-inducible gene-I-like receptors (RLR) form part of the virus detection repertoire and are critically important in sensing viral RNA in the cytoplasm. Efforts continue to define the signalling components downstream of RLR that are required to induce type I IFN (IFN-alpha and promoter stimulator-1) after viral infection. One surprising finding was that the Asp-Glu-Ala-Asp box helicase DEAD/H Box 3 (DDX3), known for some time to have a number of roles in cellular RNA regulation in the nucleus, has a role in the RLR cytoplasmic signalling pathway involved in promoter stimulator-1 induction. In this issue of the European Journal of Immunology, an article reports an additional distinct positive role for DDX3 in the RLR RNA sensing pathway. This further emphasises the importance of DDX3 in anti-viral immunity, and is consistent with the idea that viruses target DDX3 for immune evasion. PMID- 20309907 TI - Bystander activation of CD4+ T cells. AB - Bystander activation of T cells, i.e. the stimulation of unrelated (heterologous) T cells by cytokines during an Ag-specific T-cell response, has been best described for CD8(+) T cells. In the CD8(+) compartment, the release of IFN and IFN-inducers leads to the production of IL-15, which mediates the proliferation of CD8(+) T cells, notably memory-phenotype CD8(+) T cells. CD4(+) T cells also undergo bystander activation, however, the signals inducing this Ag-nonspecific stimulation of CD4(+) T cells are less well known. A study in this issue of the European Journal of Immunology sheds light on this aspect, suggesting that common gamma-chain cytokines including IL-2 might be involved in bystander activation of CD4(+) T cells. PMID- 20309908 TI - The configuration, solvatochromism and metallo-responses of two novel cyano containing oligo(phenylene-vinylene) derivatives. AB - Two novel cyano-containing oligo(phenylenevinylene) (OPV) derivatives have been designed and synthesized. Photophysical and sensing properties of the two compounds were studied. Such studies reveal the intramolecular charge transfer process between cyano groups and OPV core. The results showed that the alkyl difference of substituted OPV leads to the changes of molecular configuration and metallo-response of two compounds. PMID- 20309909 TI - A novel method for sensing of methimazole using gold nanoparticle-catalyzed chemiluminescent reaction. AB - Based on the inhibition effect of methimazole (MMI) on the reaction of luminol H(2)O(2) catalyzed by gold nanoparticles, a novel chemiluminescence (CL) method was developed for the determination of MMI. Under the optimum conditions, the relative CL intensity was linearly related to MMI concentration in the range from 5.0 * 10(-8) to 5.0 * 10(-5) mol L(-1). The detection limit was 1.6 * 10(-8) mol L(-1) (S/N=3), and the RSD for 6.0 * 10(-6) mol L(-1) MMI was 4.83 (n=11). This method has high sensitivity, wide linear range, inexpensive instrumentation and has been applied to detect MMI in pharmaceutical tablets and pig serum samples. Furthermore, a possible reaction mechanism is discussed. PMID- 20309913 TI - Heart-cutting 2D-CE with on-line preconcentration for the chiral analysis of native amino acids. AB - The use of transient moving chemical reaction boundary (tMCRB) was investigated for the on-line preconcentration of native amino acids in heart-cutting 2D-CE with multiple detection points using contactless conductivity detection. The tMCRB focusing was obtained by using ammonium formate (pH 8.56) as sample matrix and acetic acid (pH 2.3) as a BGE in the first dimension of the heart-cutting 2D CE. Different experimental parameters such as the injected volume and the concentration in ammonium formate were optimized for improving the sensitivity of detection. A stacked fraction from the first dimension was selected, isolated in the capillary, and then separated in the second dimension in the presence of a chiral selector ((+)-(18-crown-6)-2,3,11,12-tetracarboxylic acid). This on-line tMCRB preconcentration coupled with heart-cutting 2D-CE was applied with success to the chiral separation of D,L-phenylalanine, and D,L-threonine in a mixture of 22 native amino acids. The sample mixture was diluted in 0.8 M of ammonium formate, and injected at a concentration of 2.5 muM for each enantiomer with a volume corresponding to 10% of the total capillary volume. An LOD (S/N=3) of 2 muM was determined for L-threonine. PMID- 20309914 TI - Study of elution behaviour with gradient voltage in CEC using methacrylate monolithic columns. AB - A theoretical study on the retention behaviour and chromatographic performance of neutral solutes using a lauryl methacrylate-based monolithic column under voltage gradient mode in CEC was carried out. Through a flexible mathematical function based on a modified Gaussian model, the peak shape of compounds was firstly fitted under constant and gradient voltage. Using the peak shape parameters and retention time, the estimation of global chromatographic performance, efficiency and peak capacity under several voltage conditions was performed. The influence of voltage gradient on the separation efficiency is discussed and simple equations are presented to calculate retention and peak widths under voltage gradient conditions. A comparison in terms of chromatographic performance of a test mixture of neutral solutes under constant and gradient voltage modes was also carried out. The experiments carried out under gradient voltage showed better efficiencies (172,000 plates/m) and lower peak widths than those obtained under constant voltage (52,000 plates/m). PMID- 20309915 TI - Glycogen: a novel branched polysaccharide chiral selector in CE. AB - Various chiral selectors have been employed in CE and among them linear polysaccharides exhibited powerful enantioselective properties. Different from linear polysaccharides, the use of branched polysaccharides as chiral selectors in CE has not been reported previously. In this study glycogen belonging to the class of branched polysaccharides was used as a novel chiral selector for the enantiomeric separations for the first time. Since glycogen is electrically neutral, the method is applicable to ionic compounds. Eighteen chiral compounds including 12 basic drugs and six acidic drugs have been tested to demonstrate the potential of this chiral selector. BGE and selector concentrations and buffer pH were systematically optimized in order to obtain successful chiral separations. Among the tested compounds, the enantiomers of ibuprofen, which is an acidic drug, were successfully recognized by 3.0% w/v glycogen with 90 mM Tris-H(3)PO(4) buffer (pH 7.0). The enantiomers of basic drugs such as citalopram, cetirizine and nefopam were also baseline-resolved with 50 mM Tris-H(3)PO(4) buffer (pH 3.0) containing 3.0% glycogen. Amlodipine belonging to basic compound only gave partial enantioseparation under the above-mentioned condition. PMID- 20309916 TI - Generation of gold nanostructures at the surface of platinum electrode by electrodeposition for ECL detection for CE. AB - In this paper, we report a sensitive method for ECL detection for CE based on generation of gold nanostructures at the surface of Pt electrode by electrodeposition. Difenidol hydrochloride was used as a model analyte. With the increase of electrodeposition amount, the morphology of gold nanostructures changed from discrete nanoflowers to dense nanoparticle array. Interestingly, the variation of deposition amount also greatly affected the ECL intensity of difenidol. The ECL intensity increased remarkably with deposition amount and reached the maximum value at the deposition amount of 7.0 x 10(-8)C; further increasing the deposition amount, however, caused the ECL intensity to decrease. Other conditions, including applied potential, injection time and voltage, buffer pH, were also optimized in detail. Under the optimized conditions, the linear response range of difenidol is from 1.0 x 10(-8) to 5.0 x 10(-5) M, and the detection limit was 4.0 x 10(-9) M (S/N=3). The RSDs of ECL intensity and migration time were 2.0 and 1.6%, respectively (n=5, at 7.5 microM difenidol). Compared with using bare electrode, the detection sensitivity was significantly improved by ca. two orders of magnitude. Notably, the nanogold was prepared at the surface of electrode and no nanogold was added to the electrophoretic buffer or detection cell, thus causing no interference to the separation. Finally, the proposed method was successfully applied to the analysis of difenidol in tablets and urine samples. With high sensitivity and good reproducibility, this method provides a promising platform for the determination of pharmaceuticals that have a tertiary amine group such as difenidol. PMID- 20309917 TI - Novel tuneable optical elements based on nanoparticle suspensions in microfluidics. AB - This work demonstrates the application of dielectrophoretic (DEP) control of silica nanoparticles to form tuneable optical elements within a microfluidic system. The implementation consisted of a microfluidic channel with an array of curved microelectrodes along its base. Various DEP conditions were investigated at alternating current voltage amplitudes, flow rates and frequencies from 5 to 15 V, 2 to 10 microL/min and 0 to 20 MHz, respectively. The fluid channel was filled with deionized water suspending silica particles with diameters of 230 and 450 nm. Experiments were conducted to demonstrate DEP concentration and deflection of the particles and the impact of these particles distributions on the optical transmission through the fluid channel. Both confinement and scattering of the light were observed depending on the particle dimensions and the parameters of the DEP excitation. The results of this investigation illustrate the feasibility of DEP control in an optofluidic system and represent a significant step toward the dynamic formation of electrically controlled liquid optical waveguides. PMID- 20309918 TI - Type 2 diabetes and cancer: what is the connection? AB - Epidemiological studies have demonstrated an association between type 2 diabetes and cancer. Type 2 diabetes is characterized by insulin resistance and hyperinsulinemia. Hyperinsulinemia may lead to cancer through insulin's effect on its cognate receptor and the insulin-like growth factor system. The effects of insulin and insulin-like growth factor I on cancer development and progression have been demonstrated in animal and human studies. Type 2 diabetes has been positively associated with cancers of the breast, colon, and pancreas. An inverse relationship has been observed between type 2 diabetes and prostate cancer, and this may be due to lower testosterone levels in men with type 2 diabetes. Medications used to treat type 2 diabetes may affect cancer cells directly or indirectly by affecting serum insulin levels. Hyperinsulinemia may be an important risk factor for cancer as well as a target for cancer therapy. PMID- 20309919 TI - Colonoscopy versus computed tomography colonography for colorectal cancer screening. AB - Colorectal cancer is second only to lung cancer as the leading cause of death among North Americans of both sexes. Although screening rates for colorectal cancer in the United States have increased over the past decade, these rates (in the range of 45%-60%) are still lower than the screening rates for breast cancer (approximately 80%). Optical colonoscopy has been recognized as the preferred method for colorectal cancer screening in the United States, but computed tomography colonography has recently been gaining favor. This article compares the 2 methods with respect to both advantages and disadvantages. PMID- 20309920 TI - Epigenetics in women's health care. AB - Epigenetics refers to structural modifications to genes that do not change the nucleotide sequence itself but instead control and regulate gene expression. DNA methylation, histone modification, and RNA regulation are some of the mechanisms involved in epigenetic modification. Epigenetic changes are believed to be a result of changes in an organism's environment that result in fixed and permanent changes in most differentiated cells. Some environmental changes that have been linked to epigenetic changes include starvation, folic acid, and various chemical exposures. There are periods in an organism's life cycle in which the organism is particularly susceptible to epigenetic influences; these include fertilization, gametogenesis, and early embryo development. These are also windows of opportunity for interventions during the reproductive life cycle of women to improve maternal-child health. New data suggest that epigenetic influences might be involved in the regulation of fetal development and the pathophysiology of adult diseases such as cancer, diabetes, obesity, and neurodevelopmental disorders. Various epigenetic mechanisms may also be involved in the pathogenesis of preeclampsia and intrauterine growth restriction. Additionally, environmental exposures are being held responsible for causing epigenetic changes that lead to a disease process. Exposure to heavy metals, bioflavonoids, and endocrine disruptors, such as bisphenol A and phthalates, has been shown to affect the epigenetic memory of an organism. Their long-term effects are unclear at this point, but many ongoing studies are attempting to elucidate the pathophysiological effects of such gene-environment interactions. PMID- 20309921 TI - Genes, race, ethnicity, and environment. PMID- 20309922 TI - Race, ethnicity, ancestry, and pharmacogenetics. AB - Pharmacogenetics is the study of how genetic variation influences the response to drugs. The concepts of race, ethnicity, and ancestry have long had a strong influence on pharmacogenetic discovery and on our understanding of population level differences in drug response. The primary goal of pharmacogenetics, however, is to identify the individual genetic determinants of drug activity so that therapy can be tailored to the individual patient. This article describes the relationship between the concepts of race, ethnicity, and ancestry and how these concepts have been applied to pharmacogenetics, and it provides examples of the benefits and pitfalls associated with the use of racial or ethnic labels in genetic studies. The future of pharmacogenetics, including the study of rare genetic variation and what this means for racial or ethnic disparities in pharmacogenetic discovery, is also discussed. PMID- 20309923 TI - You are born with your genes: justice and protection against discrimination in the use of genetic information. AB - Genetic information poses an apparent paradox for justice in health care. On the one hand, genetic information seems to be exactly the kind of information that it is unjust to take into account in the distribution of important goods. On the other hand, genetic information may increasingly become useful in individual patient care as evidence for personalized medicine increases. Although it is important to emphasize the difference between genetic information and the social construct of race, nonetheless, the historical interplay between discrimination based on assumptions about heritability and discrimination based on race are significant. Thus, this article defends the importance of paying very close attention to protections in the use of genetic information. Three current examples of inadequate protection are cited. First, informed consent to genetic testing should incorporate potential confidentiality risks raised by this information. Second, the Genetic Information Nondiscrimination Act is too porous to protect employees from their employers' possession of genetic information; if such information is used in discriminatory ways, burdens of seeking protection then fall on the employees. More stringent strategies for protecting information are thus desirable. Finally, current designs of interoperable health records fail to allow for the sequestration of genetic information. Efforts to develop such sequestration techniques should be encouraged; among other benefits, they would be helpful in shielding genetic information from employers. PMID- 20309924 TI - Genetics and asthma disease susceptibility in the US Latino population. AB - The US Latino population is heterogeneous with diversity in environmental exposures and socioeconomic status. Moreover, the US Hispanic population derives from numerous countries previously under Spanish rule, and many Hispanics have complex proportions of European, Native American, and African ancestry. Disparities in asthma severity and control are due to complex interactions between environmental exposures, socioeconomic factors, and genetic variations. In addition, diseases within the Latino community may also differ by country of origin. Although US Census data show low asthma rates in the Hispanic population as a whole, there is a lot of variability in the prevalence and morbidity of asthma, with a prevalence of 5.0% in Mexican Americans versus 17.0% in Puerto Ricans. The diversity and population admixture make the study of the genetics of asthma complex in Latino populations. However, an understanding of the genetics of asthma in all populations, including the Latino population, can enhance risk identification, help us to target pharmacological therapy, and guide environmental regulations, all of which can promote a reduction in health disparities. The inclusion of markers of ancestral diversity and the incorporation of techniques to adjust for stratification now make these studies feasible in complex populations, including the Latino population. To date, studies using linkage analyses, genome-wide associations, or candidate gene analyses have identified an association of asthma or asthma-related phenotypes with candidate genes, including interleukin 13, beta-2 adrenergic receptor, a disintegrin and metalloproteinase 33, orosomucoid 1-like 3, and thymic stromal lymphopoietin. As reviewed here, although these genes have been identified in diverse populations, limited studies have been performed in Latino populations, and they have had variable replication. There is a need for the development of registries with well-phenotyped pediatric and adult Latino populations and subgroups for inclusion in the rapidly expanding field of genetic studies, and these studies need to be used to reduce health disparities. PMID- 20309925 TI - Is there a genetic basis for health disparities in human immunodeficiency virus disease? AB - The highest global prevalence rates for human immunodeficiency virus and acquired immune deficiency syndrome have been recorded in southern Africa; in the United States, individuals of African descent are disproportionately affected by human immunodeficiency virus infection. Human immunodeficiency virus-infected individuals with African ancestry are also estimated to have a 17-fold or greater risk for developing human immunodeficiency virus-associated nephropathy in comparison with their counterparts of non-African descent. Several recent studies have implicated genetic alleles that are more frequent in populations of African descent and increase the risk of human immunodeficiency virus infection and the risk of human immunodeficiency virus-associated neuropathy (HIVAN). The supposition that persons of African descent are more susceptible to human immunodeficiency virus infection because of an underlying genetic predisposition is not supported by available evidence. However, strong, replicated data show that the increased risk for human immunodeficiency virus-associated nephropathy, as well as other major forms of kidney disease in individuals of African descent, is due in part to MYH9 (myosin, heavy chain 9, non-muscle) renal disease susceptibility alleles that are very frequent throughout sub-Saharan Africa but are infrequent or absent in non-Africans. Selection, drift, and demographic events shape the allelic architecture of the human genome: it is expected that these events will be reflected in geographic-specific differentiation in allele frequencies for a small subset of alleles that may be associated with either increased or reduced risk for complex and infectious diseases. PMID- 20309926 TI - Genetic and environmental contributions to racial disparities in preterm birth. AB - The preterm birth rate exceeds 12% in the United States, and preterm birth continues to be a clinical and public health challenge globally. Even though preterm birth is a major contributor to infant mortality and lifelong morbidity, there are few effective strategies to predict preterm birth and few clinical interventions to prevent it. Genomic research approaches that identify risk factors at the intersection of genetics and the environment will likely provide insights. Both genetic and environmental factors are known to contribute to the racial disparity seen in preterm birth. Through the identification of relevant gene-environment interactions that contribute to preterm birth and may underlie the racial disparity in preterm birth, research that will translate to clinical practice and ultimately prevent a number of preterm births is possible. PMID- 20309927 TI - Access to health and health care: how race and ethnicity matter. AB - Racial and ethnic disparities in health are multifactorial; they reflect differences in biological vulnerability to disease as well as differences in social resources, environmental factors, and health care interventions. Understanding and intervening in health inequity require an understanding of the disparate access to all of the personal resources and environmental conditions that are needed to generate and sustain health, a set of circumstances that constitute access to health. These include access to health information, participation in health promotion and disease prevention activities, safe housing, nutritious foods, convenient exercise spaces, freedom from ambient violence, adequate social support, communities with social capital, and access to quality health care. Access to health care is facilitated by health insurance, a regular source of care, and a usual primary care provider. Various mechanisms through which access to health and access to health care are mediated by race and ethnicity are discussed; these include the built environment, social environment, residential segregation, stress, racism, and discrimination. Empirical evidence supporting the association between these factors and health inequities is also reviewed. PMID- 20309929 TI - Triblock copolymer matrix-based capillary electrophoretic microdevice for high resolution multiplex pathogen detection. AB - Rapid and simple analysis for the multiple target pathogens is critical for patient management. CE-SSCP analysis on a microchip provides high speed, high sensitivity, and a portable genetic analysis platform in molecular diagnostic fields. The capability of separating ssDNA molecules in a capillary electrophoretic microchannel with high resolution is a critical issue to perform the precise interpretation in the electropherogram. In this study, we explored the potential of poly(ethyleneoxide)-poly(propyleneoxide)-poly(ethyleneoxide) (PEO-PPO-PEO) triblock copolymer as a sieving matrix for CE-SSCP analysis on a microdevice. To demonstrate the superior resolving power of PEO-PPO-PEO copolymers, 255-bp PCR amplicons obtained from 16S ribosomal RNA genes of four bacterial species, namely Proteus mirabilis, Haemophilus ducreyi, Pseudomonas aeruginosa, and Neisseria meningitidis, were analyzed in the PEO-PPO-PEO matrix in comparison with 5% linear polyacrylamide and commercial GeneScan gel. Due to enhanced dynamic coating and sieving ability, PEO-PPO-PEO copolymer displayed fourfold enhancement of resolving power in the CE-SSCP to separate same-sized DNA molecules. Fivefold input of genomic DNA of P. aeruginosa and/or N. meningitidis produced proportionally increased corresponding amplicon peaks, enabling correct quantitative analysis in the pathogen detection. Besides the high-resolution sieving capability, a facile loading and replenishment of gel in the microchannel due to thermally reversible gelation property makes PEO-PPO-PEO triblock copolymer an excellent matrix in the CE-SSCP analysis on the microdevice. PMID- 20309928 TI - Environmental justice and the health of children. AB - Environmental injustice is the inequitable and disproportionately heavy exposure of poor, minority, and disenfranchised populations to toxic chemicals and other environmental hazards. Environmental injustice contributes to disparities in health status across populations of differing ethnicity, race, and socioeconomic status. Infants and children, because of their unique biological vulnerabilities and age-related patterns of exposure, are especially vulnerable to the health impacts of environmental injustice. These impacts are illustrated by sharp disparities across children of different racial and ethnic backgrounds in the prevalence of 3 common diseases caused in part by environmental factors: asthma, lead poisoning, and obesity. Documentation of linkages between health disparities and environmental injustice is an important step toward achieving environmental justice. PMID- 20309932 TI - Microchip electrophoresis of Alu elements for gender determination and inference of human ethnic origin. AB - We performed a series of multi-locus PCRs followed by the rapid and efficient microchip electrophoretic sorting of Alu products with LIF detection. Five polymorphic human-specific Alu insertions (RC5, A1, PV92, TPA and ACE) were used for inference of human ethnicity and two monomorphic Alu insertions for sex typing, one fixed on the X chromosome (AluSTXa) and the other on the Y chromosome (AluSTYa). These markers were used to generate unique DNA profiles for five different DNA samples. The PCR-based assays used primers that flank the insertion point to determine genotypes based on the presence or absence of the Alu element. A1, RC5, PV92, TPA and ACE were used for ethnicity determinations and have two alleles, each indicating the presence (+) or absence (-) of the Alu element on the paired chromosomes, which results in three genotypes (+/+, +/- or -/-). RC5 and A1 did not show ethnic heterogeneity resulting in a homozygous (-/-) genotype, which correctly inferred that DNA samples originating from a Caucasian male and an Asian male were not of African ancestry. The results from the five Alu markers indicated that these Alu loci could assist in identifying the individual's ethnicity using microchip electrophoresis in under 15 min of separation time. Using microchip electrophoresis and mixed genotype ratios, male DNA-to-female DNA of 1:9, corresponding to a ratio of Y-to-X chromosomes of 1:19, was also detected for both AluSTXa and AluSTYa to provide gender identification without requiring separation of female from male cells prior to the assay. PMID- 20309933 TI - p53 transactivation is involved in the antiproliferative activity of the putative tumor suppressor RBM5. AB - RBM5 (RNA-binding motif protein 5) is a nuclear RNA binding protein containing 2 RNA recognition motifs. The RBM5 gene is located at the tumor suppressor locus 3p21.3. Deletion of this locus is the most frequent genetic alteration in lung cancer, but is also found in other human cancers. RBM5 is known to induce apoptosis and cell cycle arrest but the molecular mechanisms of RBM5 function are poorly understood. Here, we show that RBM5 is important for the activity of the tumor suppressor protein p53. Overexpression of RBM5 enhanced p53-mediated inhibition of cell growth and colony formation. Expression of RBM5 augmented p53 transcriptional activity in reporter gene assays and resulted in increased mRNA and protein levels for endogenous p53 target genes. In contrast, shRNA-mediated knockdown of endogenous RBM5 led to decreased p53 transcriptional activity and reduced levels of mRNA and protein for endogenous p53 target genes. RBM5 affected protein, but not mRNA, levels of endogenous p53 after DNA damage suggest that RBM5 contributes to p53 activity through post-transcriptional mechanisms. Our results show that RBM5 contributes to p53 transcriptional activity after DNA damage and that growth suppression and apoptosis mediated by RBM5 are linked to activity of the tumor suppressor protein p53. PMID- 20309934 TI - Transformation of benign Barrett's epithelium by repeated acid and bile exposure over 65 weeks: a novel in vitro model. AB - The mechanism by which gastroesophageal reflux promotes metaplasia->dysplasia >carcinoma is unknown. The aim of the study is to determine if repeated exposure to acid and bile confers a tumorigenic phenotype in a telomerase (hTERT) immortalized benign Barrett's cell line (BAR-T). BAR-T cells were exposed to acid (pH 4) (A) and bile salt (200 MUM glycochenodeoxycholic acid) (B) daily for 5 min up to 65+ weeks. The control cells were grown in parallel without any A or B treatment. Cell morphology, proliferation, transformation, and molecular changes in the gene expression for COX-2, TC22, p53 and p53 target genes were analyzed at 8-12 weeks intervals. At 46 weeks BAR-T cells exposed to (A+B) showed distinct phenotypic changes: forming clusters and acini, and at 65 weeks displayed foci in monolayer, and formed distinct colonies in soft agar. Untreated cells did not show any such changes. In A+B-treated BAR-T cells, COX-2 mRNA increased 10- to 20 fold, TC22 mRNA increased by 2- to 3-fold at 22-65 weeks, p53, MDM2, PERP, and p21mRNA increased 2.5-, 6.4-, 4-, and 2.6-fold respectively when compared to untreated cells at 34 weeks. However, at 58 weeks onward, there was a sharp decline of p53 and its target genes to the baseline level. At 65 weeks A+B treated BAR-T cells formed tumor in nude mice whereas untreated cells did not. We demonstrate a novel in vitro model of transformation of a benign Barrett's cell line following repeated exposure to A+B over the course of 65 weeks. PMID- 20309936 TI - ABO blood group and incidence of epithelial ovarian cancer. AB - Previous studies have observed an association between ABO blood group and risk of certain malignancies, including ovarian cancer; however, no prospective studies of the association with ovarian cancer risk are available. Using data from 49,153 women in the Nurses' Health Study, we examined the association between ABO blood group and incidence of epithelial ovarian cancer. Study participants reported their blood type and Rh factor in 1996, and 234 women were diagnosed with incident ovarian cancer during 10 years of follow-up. We used Cox proportional hazards regression to model the incidence rate ratios (RR) and 95% confidence intervals (CI) of ovarian cancer for each blood group category. Compared to women with blood group O, women with blood group AB or B had a nonsignificant 38% increase in ovarian cancer incidence (95% CI = 0.88-2.16 for blood group AB and 0.96-1.99 for blood group B), whereas blood group A was not associated with risk (RR = 0.95, 95% CI = 0.70-1.30). Combining blood groups AB and B, we observed a statistically significant positive association with presence versus absence of the B antigen overall (RR = 1.41, 95% CI = 1.06-1.88) and for the serous invasive subtype (RR = 1.53, 95% CI = 1.08-2.17). In this large, prospective cohort of women, presence of the B antigen was positively associated with ovarian cancer incidence, whereas blood group A was not associated with risk. Additional studies are needed to confirm this association and to explore the mechanisms through which blood group may influence ovarian cancer risk. PMID- 20309937 TI - The leader peptide of a human rec. MnSOD as molecular carrier which delivers high amounts of Cisplatin into tumor cells inducing a fast apoptosis in vitro. AB - The leader peptide of a recombinant MnSOD (rMnSOD-Lp) constitutes the carrier that allows rMnSOD to penetrate tumor cells. A synthetic preparation of rMnSOD-Lp was 68Ga labeled (rMnSOD-Lp- 68Ga) and injected into animals bearing spontaneous mammary cancers, followed by PET examinations, which demonstrated unambiguously the tumor sites in all the animals, suggesting that if rMnSOD-Lp was able to transport the radioisotope into tumor cells, it would also be able to deliver cytotoxic molecules. The rMnSOD-Lp was, therefore, conjugated to cisplatin (rMnSOD-Lp-CC) and added to cultured tumor cells. Equal concentrations of cisplatin were used for the tests. After treating the ovarian cancer cells with 11.1 MUg of cisplatin alone, analysis by atomic absorbance spectrophotometry was able to detect only 6 ng of platinum, whereas when the same cells were treated with the same amount of cisplatin conjugated to leader peptide rMnSOD, 387 ng of platinum were detected, i.e., an amount 80 times greater. Only the tumor cells died following treatment with rMnSOD-Lp-CC; molecular analysis revealed that its addition generated an increasing expression of Erk-2 and Bax products, which could be inhibited only by a selective MAP/ERK kinase inhibitor (PD98059), revealing that rMnSOD-Lp-CC has an apoptotic function, exactly as occurs when using the cisplatin alone. Data are statistically significant and indicate that by using rMnSOD-Lp-CC, the cisplatin can be transformed from an agent with antireplicative activity into a specific and selective antitumor molecule, increasing its therapeutic index. We think that rMnSOD-Lp-CC deserves to be considered as a new antitumor agent. PMID- 20309938 TI - Intratumoral injection of interferon-alpha and systemic delivery of agonist anti CD137 monoclonal antibodies synergize for immunotherapy. AB - CD137 artificial costimulation results in complete tumor rejection in several mouse models. Type I interferons (IFN) exert antitumor effects through an array of molecular functions on malignant cells, tumor stroma and immune system cells. The fact that agonist anti-CD137 mAb induce tumor regressions in mice deficient in the unique receptor for Type I IFNs (IFNAR(-/-) ) indicated potential for treatment combinations. Indeed, combination of intratumor injections of mouse IFN alpha and intraperitoneal injections of anti-CD137 mAb synergized as seen on subcutaneous lesions derived from the MC38 colon carcinoma, which is resistant to each treatment if given separately. Therapeutic activity was achieved both against lesions directly injected with IFN-alpha and against distant concomitant tumors. Experiments in bone marrow chimeras prepared with IFNAR(-/-) and WT mice concluded that expression of the receptor for Type I interferons is mainly required on cells of the hematopoietic compartment. Synergistic effects correlated with a remarkable cellular hyperplasia of the tumor draining lymph nodes (TDLNs). Enlarged TDLNs contained more plasmacytoid and conventional dendritic cells (DC) that more readily cross-presented. Importantly, numbers of both DC subtypes inversely correlated with the tumor size. Numbers of CD8 T cells specific for a dominant tumor antigen were increased at TDLNs by each separate treatment but only with slight augments due to the combination. Combined antitumor effects of the therapeutic strategy were also seen on subcutaneous TC-1 tumors established for 24 days before treatment onset. The described strategy is realistic because (i) agents of each kind are clinically available and (ii) equivalent procedures in humans are feasible. PMID- 20309939 TI - The combination of TLR-9 adjuvantation and electroporation-mediated delivery enhances in vivo antitumor responses after vaccination with HPV-16 E7 encoding DNA. AB - Therapeutic DNA vaccination is an attractive adjuvant option to conventional methods in the fight against cancer, like surgery radiotherapy and chemotherapy. Despite strong antitumor effects that were observed in small animals with different antigens, DNA-based vaccines remain weakly immunogenic in large animals and primates compared to protein-based vaccines. Here, we sought to enhance the immunogenicity of a therapeutic nontransforming cervical cancer DNA vaccine (HPV 16 E7SH) by introduction of a highly optimized CpG cassette into the plasmid backbone as well as by an optimized DNA delivery using an advanced electroporation (EP) technology. By integrating the means for agent administration and EP into a single device, this technology enables a simple, one step procedure that facilitates reproducibility. We found that highly optimized CpG motifs alone triggers an enhanced IFN-gamma and granzyme B response in Elispot assays as well as stronger tumor regression. Furthermore, these effects could be dramatically enhanced when the CpG cassette containing plasmid was administered via the newly developed EP technology. These data suggest that an optimized application of CpG-enriched DNA vaccines may be an attractive strategy for the treatment of cancer. Collectively, these results provide a basis for the transfer of preclinical therapeutic DNA-based immunization studies into successful clinical cancer trials. PMID- 20309940 TI - A potentially functional polymorphism in the promoter region of miR-34b/c is associated with an increased risk for primary hepatocellular carcinoma. AB - The miR-34 family members are direct transcriptional targets of tumor suppressor p53, and loss of miR-34 function can impair p53-mediated cell cycle arrest and apoptosis. A potentially functional SNP rs4938723 (T > C) was found in the promoter region of pri-miR-34b/c (423 bp from the transcription start site), located in the CpG island and might affect transcription factor GATA binding and therefore pri-miR-34b/c expression. In our study, we hypothesized that SNPs miR 34b/c rs4938723 and TP53 Arg72Pro may independently or jointly contribute to primary hepatocellular carcinoma (HCC) susceptibility. We then genotyped the 2 SNPs in a case-control study of 501 patients with primary HCC and 548 cancer-free controls in a Chinese population. We observed that the variant genotypes of miR 34b/c rs4938723 were associated with significantly increased HCC risks compared with the wild-type TT genotype (adjusted OR = 1.37, 95% CI =1.06-1.78 for TC; OR = 1.53, 95% CI = 1.02-2.31 for CC and OR = 1.40, 95% CI = 1.10-1.80 for TC/CC). Furthermore, we found a significant interaction between alcohol drinking and SNP rs4938723 on HCC risk (p = 0.05 for multiplicative and p = 0.01 for additive interaction). However, we did not find any main effect of TP53 Arg72Pro on HCC risk in this population. These findings indicate that the potentially functional SNP rs4938723 in the promoter region of pri-miR-34b/c may contribute to the susceptibility of HCC in this Chinese population. PMID- 20309941 TI - Effects of tyroservatide on histone acetylation in lung carcinoma cells. AB - Tyroservatide (YSV) is an active, low-molecular weight polypeptide shown to have antitumor effects on experimental hepatocarcinoma and lung carcinoma. The focus of our study was to observe the effects of YSV on several human lung carcinoma cell lines and explore its antitumor mechanism via its effect on histone acetylation. Our results showed that YSV significantly inhibited the proliferation of human lung carcinoma A549, NCIH460, NCIH292 and NCIH1299 cells, induced G(0) /G(1) cell cycle arrest and increased protein and mRNA levels of p21 and p27. Moreover, YSV treatment significantly inhibited histone deacetylase (HDAC) activity and resulted in the accumulation of acetylated histones H3 and H4 in total cellular chromatin and p21 gene-associated chromatin regions. Together these data suggest that the antitumor effects of YSV might be mediated by its inhibition of HDAC activity, selectively upregulating the expression of p21 by increasing the acetylation of histones associated with p21 gene regions, resulting in an induction of G0/G1 cell cycle arrest and inhibition of the proliferation of tumor cells. Our findings demonstrate that YSV may exhibit potent therapeutical effects on lung carcinoma. PMID- 20309942 TI - Lysophosphatidic acid-induced expression of periostin in stromal cells: Prognoistic relevance of periostin expression in epithelial ovarian cancer. AB - Lysophosphatidic acid (LPA) is a bioactive lipid crucial for the initiation and progression of ovarian cancer. Identification of LPA-induced biomarkers is necessary for predicting prognosis of ovarian cancer patients. Here we report periostin, an extracellular matrix protein, as an LPA-induced protein in stromal cells and as a prognostic marker in patients with epithelial ovarian cancer (EOC). In human EOC tissues, periostin was mainly expressed in cancer-associated stromal fibroblasts, but not in cancer cells. The expression levels of periostin highly correlated with poor survival and tumor recurrence of ovarian cancer patients. Treatment of human adipose tissue-derived stromal cells with LPA or conditioned media from human ovarian adenocarcinoma cell lines, such as SK-OV-3 and OVCAR-3, induced expression of periostin. The periostin expression induced by cancer-conditioned media was abrogated by silencing of the LPA receptor 1 expression using small hairpin RNA lentivirus. Recombinant periostin stimulated adhesion and invasion of SK-OV-3 human ovarian adenocarcinoma cells and induced expression of matrix metalloprotease-2 in the cancer cells. These results suggest that LPA is associated with the expression of periostin in cancer-associated fibroblasts of EOC. PMID- 20309943 TI - Adiposity, adult weight gain and mammographic breast density in US Chinese women. AB - The association of adiposity with dense tissue area in the breast is unclear, but suggests a mechanism by which adiposity might increase breast cancer risk. We examined associations of body mass index (BMI), usual BMI from age 20 to 29, waist circumference and adult weight gain with breast density in a sample of premenopausal United States Chinese immigrant women. Analyses included 415 participants in a longitudinal breast density study in Philadelphia. In addition to detailed questionnaire information, data collection included measures of anthropometry, and assessment of mammographic breast density using a computer assisted method. We used multivariate linear regression to quantify cross sectional associations with dense and nondense tissue area and percent breast density assessed at baseline. In adjusted models, BMI and waist circumference were significantly positively associated with nondense tissue area and inversely associated with percent density. BMI was also significantly positively associated with dense tissue area. Adult weight gain was associated with dense tissue area after adjusting for weight from age 20 to 29. In stratified analyses, BMI and adult weight gain were significantly associated with dense tissue area among women with BMI < 23 kg/m2, and BMI was associated with nondense tissue area among women with BMI >= 23 kg/m2. In this sample, adiposity and weight gain were associated with dense breast tissue area, although associations differed by level of adiposity. Given the potential implications of these findings for breast cancer prevention in premenopausal women, comparable studies in other population groups and with longitudinal data are needed. Reasons for the noted differences in associations by level of adiposity also warrant further investigation. PMID- 20309944 TI - Gastric cancers in Finnish patients after cure of Helicobacter pylori infection: A cohort study. AB - Helicobacter pylori infection is associated with gastric cancer. A total of 97% of the infected subjects have elevated levels of H. pylori antibodies. The antibody titers have been shown to decline rapidly (40-60% within 4-12 months) only after successful eradication therapy. We allocated 26,700 consecutive patients tested during 1986-1998 for H. pylori antibodies to 3 subcohorts: seropositive patients with rapidly falling antibody titers (Hp+CURED, n = 3,650), seropositive patients where no serological information indicating cure was obtained (Hp+NoInfo, n = 11,638) and seronegative patients (Hp-, n = 11,422). In the subcohorts, the standardised incidence ratios (SIRs) with 95% confidence intervals (CI) were defined for subsequent cancers of stomach, pancreas, colon, rectum, breast and prostate separately and for all cancers except stomach combined. The mean follow-up time was 10.1 years and the number of gastric cancers was 72. For the Hp+CURED, the SIR for gastric cancers for the first 5 follow-up years was 1.62 but decreased from the sixth follow-up year thereon to 0.14 (CI: 0.00-0.75). Likewise, the risk ratio, defined in a Poisson regression analysis using the Hp+NoInfo group as the reference, decreased from 1.60 to 0.13 (CI: 0.02-1.00, p = 0.049). The SIR for Hp- was not significantly higher than that for Hp+NoInfo for any of the cancers analysed. To conclude, cured H. pylori infection led to a significantly decreased incidence of gastric cancers from the sixth follow-up year. Advanced atrophic gastritis would be a plausible contributor to the elevated SIR in elderly Hp- patients. PMID- 20309945 TI - Hsa-let-7g inhibits proliferation of hepatocellular carcinoma cells by downregulation of c-Myc and upregulation of p16(INK4A). AB - zMicroRNAs (miRNAs) are endogenously expressed small noncoding RNAs that regulate approximately one-third of human genes at post-transcription level. Previous studies have shown that miRNAs were implicated in many cellular processes and participated in the progress of various tumors including hepatocellular carcinoma (HCC). Among all miRNAs, the let-7 family is well recognized to play pivotal roles in tumorigenesis by functioning as potential growth suppressor. In the present study, we aimed to investigate the role of let-7 family, particularly the hsa-let-7g, in the molecular pathogenesis of HCC. By use of MTT, qPCR, Western blotting and 2-dimensional electrophoresis (2-DE), over-expression of hsa-let-7g was found to inhibit the proliferation of HCC cell line via negative and positive regulations of c-Myc and p16(INK4A) , respectively. The expression of hsa-let-7g was noted to be markedly lowered in the HepG2, Hep3B and Huh7 cells, yet higher in the Bel-7404 HCC cell line. Proliferation of HCC cell line was significantly inhibited after the transfection of hsa-let-7g mimics, while hsa-let-7g inhibitor transfection exerted an opposite effect. Concurrently, the mRNA and protein levels of c-Myc were found significantly decreased in HepG2 cells after transfection of hsa-let-7g mimics, but obviously increased in Bel-7404 cells after transfection of hsa-let-7g inhibitor. As revealed by 2-DE, a significant upregulation of p16(INK4A) was revealed after the gain-of-function study using hsa-let-7g. Therefore, we suggest that hsa-let-7g may act as a tumor suppressor gene that inhibits HCC cell proliferation by downregulating the oncogene, c-Myc, and upregulating the tumor suppressor gene, p16(INK4A) . PMID- 20309946 TI - Identification of EGFR mutations in lung sarcomatoid carcinoma. PMID- 20309947 TI - Value of a modified clinical signs and symptoms of infection checklist for leg ulcer management. AB - BACKGROUND: The aim of this study was to analyse the validity of a modified Clinical Signs and Symptoms Checklist used to measure infection in a sample of patients with a leg ulcer. METHODS: Data from patients recruited to a randomized controlled trial evaluating larval therapy (VenUS II) were analysed using factor analysis to identify the underlying checklist structure. Linear regression analysis identified whether checklist items, patient characteristics and subjective judgement of infection could predict bacterial load. RESULTS: There were several redundant checklist items when implemented in this sample and items forming the scale had low internal consistency (alpha = 0.27). No clear structure to the checklist was detected, with only one underlying theme revealed which had low internal consistency (alpha = 0.45). Predictions of bacterial count were possible using the emerged theme, some checklist items and ankle circumference, but not using clinicians' subjective judgement alone (P = 0.315). CONCLUSION: The modified Clinical Signs and Symptoms Checklist does not currently represent a valid tool to measure infection in leg ulcers. Some checklist items may predict bacterial load and may be better than subjective judgement alone. PMID- 20309948 TI - Intraoperative near-infrared image-guided surgery for peritoneal carcinomatosis in a preclinical experimental model. AB - BACKGROUND: This study compared the quality of surgery performed under conventional light with near-infrared (NIR) image-guided surgery using a tumour targeting probe and a portable clinical grade imaging device in a mouse model of peritoneal carcinomatosis. METHODS: Peritoneal carcinomatosis was induced by injection of luciferase-positive tumour cells, leading to the formation of small nodules in the peritoneal cavity. One day after intravenous injection of RAFT c(RGDfK)4-Alexa Fluor 700, a fluorescent tumour-targeting probe, the surgeon operated using the Fluobeam, a portable device that illuminated the mouse with NIR light and allowed NIR vision. The quality of the surgery was evaluated using bioluminescence, a highly sensitive method that detected the remaining tumour cells, and operating time was measured. RESULTS: Under normal light, the surgeon detected and removed a mean(s.d.) of only 50.6(2.3) per cent of the nodules that were visible under NIR light. The duration of surgery was reduced from 19.5(3.3) min under normal light to 14.0(2.6) min when NIR light was used (P = 0.025). The sensitivity of the NIR system allowed the detection of nodules containing as few as 227 tumour cells. CONCLUSION: NIR image-guided surgery improved the quality of surgery for peritoneal carcinomatosis by doubling the number of nodules detected and significantly reducing the duration of surgery. PMID- 20309949 TI - Antihyperglycaemic and protective effects of flavonoids on streptozotocin-induced diabetic rats. AB - The antihyperglycaemic effect of eight standard flavonoids, previously identified in the ethanol extract of the claimed antidiabetic plant Genista tenera, was evaluated on streptozotocin (STZ)-induced diabetic Wistar rats. The aglycones apigenin, chrysoeriol and genistein, the monoglucosides apigenin 7-O-glucoside, luteolin 7-O-glucoside and genistein 7-O-glucoside and the diglycosides rutin and luteolin 7,3'-di-O-glucoside were administered i.p. for 7 days (4 mg/kg b.w./day). The protective effect of these compounds over liver and kidneys of STZ diabetic models was also evaluated by the determination of seric AST, ALT and urea levels. After 7 days of treatment, apigenin, chrysoeriol and genistein significantly lowered the blood glucose levels of diabetic animals; this effect was more pronounced (P < 0.01) in the oral glucose tolerance test. Glucose tolerance was also significantly improved in the rutin (P < 0.01) and in the genistein 7-O-glucoside (P < 0.05) treated groups. In addition, almost all the tested compounds effectively protected the liver and kidneys against STZ-induced damage in rats. PMID- 20309950 TI - Bioactivity of a flavanol-rich lychee fruit extract in adipocytes and its effects on oxidant defense and indices of metabolic syndrome in animal models. AB - Many polyphenolic compounds are poorly digested, and have low bioavailability due to their long chain lengths and chemical composition. A processed, flavanol-rich lychee fruit extract (FRLFE) that is higher in flavanol monomers, dimer and trimers than its unprocessed counterpart, was tested in a variety of models. First, mature visceral adipocytes were treated with 0, 3, 10 or 30 microg/mL FRLFE (day 6-8). Compared with the controls, the treated cells had lower triglyceride concentrations, less lipid accumulation and a smaller lipid droplet size. Adiponectin release was significantly greater in cells receiving 3 or 10 microg/mL FRLFE than in the controls. Second, rats given a single dose of 50 or 100 mg/kg FRLFE had significant increases in plasma (-)-epicatechin, 3'-O-methyl (-)-epicatechin, and (+)-catechin levels, peak values were at approximately 2 h and appreciable concentrations were still detected at 6 h. Rats supplemented daily for 1 week with 50 or 100 mg/kg FRLFE had significantly elevated metabolite concentrations. In response to an oxidative stress, erythrocyte membrane integrity was significantly improved in the 100 mg/kg FRLFE group. Third, 7-month old mice fed a 200 mg/kg FRLFE diet for 10 months showed a significant decrease in glucose, triglyceride and lipid peroxide levels compared with mice fed a control diet. Collectively, these results support the concept that the flavanols present in FRLFE are well absorbed and bioactive. PMID- 20309951 TI - Influence of muscle training on resting blood flow and forearm vessel diameter in patients with chronic renal failure. AB - BACKGROUND: Blood flow and vessel diameter are predictors of the success of vascular access procedures. This study investigated whether a simple exercise programme could influence these variables. METHODS: Twenty-three patients with chronic kidney disease were prescribed a simple exercise programme for one arm only; the investigators were blinded to the patients' choice. All underwent arterial and venous duplex imaging, handgrip strength and blood pressure measurements before and 1 month after the exercise programme. RESULTS: Twelve patients exercised their dominant and 11 their non-dominant arm. In the trained arm, the exercise programme resulted in a significant increase in handgrip strength, by a median (interquartile range) of 4 (0-8) kg (P < 0.001), and in the diameter of the brachial artery (0.2 (0.1-0.3) mm; P < 0.001), radial artery (0.3 (0.2-0.4) mm; P < 0.001), and cephalic vein (0.6 (0.4-1.2) mm in the forearm and 1.1 (0.4-1.2) mm above the elbow; P < 0.001). There was an increase in brachial artery mean velocity (3 (1-7) cm/s; P = 0.009) and peak systolic velocity (8 (1 15) cm/s; P = 0.020), despite a marginally lower systolic blood pressure (-8 (-16 to 0) mmHg; P = 0.007). There was no change in any of these parameters in the non exercised arm. CONCLUSION: In patients with chronic kidney disease, forearm exercise increased blood flow and vessel diameters. This may be beneficial before vascular access formation. PMID- 20309953 TI - Two different pathways for suprascapular intraneural ganglion cysts along two distinct articular branches from the glenohumeral joint. PMID- 20309952 TI - Osteoblastic differentiation of human and equine adult bone marrow-derived mesenchymal stem cells when BMP-2 or BMP-7 homodimer genetic modification is compared to BMP-2/7 heterodimer genetic modification in the presence and absence of dexamethasone. AB - Bone marrow-derived mesenchymal stem cells (BMDMSCs) have been targeted for use in enhancement of bone healing; and their osteogenic potential may be further augmented by genes encoding bone morphogenetic proteins (BMP's). The purpose of this study was to compare the effect of genetic modification of human and equine BMDMSCs with BMP-2 or -7 or BMP-2 and -7 on their osteoblastogenic differentiation in the presence or absence of dexamethasone. The BMDMSCs were harvested from the iliac crest of three human donors and tuber coxae of three equine donors. Monolayer cells were genetically modified using adenovirus vectors encoding BMP-2, -7 or both and cultured in the presence or absence of dexamethasone. Expression of BMPs was confirmed by enzyme linked immunosorbent assay (ELISA). To evaluate osteoblastic differentiation, cellular morphology was assessed every other day and expression and secretion of alkaline phosphatase (ALP), as well as expression levels of osteonectin (OSTN), osteocalcin (OCN), and runt-related transcription factor-2 (Runx2) were measured for up to 14 days. Human and equine BMDMSCs showed a capacity for osteogenic differentiation regardless of genetic modification or dexamethasone supplementation. Dexamethasone supplementation was more important for osteoblastogenic differentiation of equine BMDMSCs than human BMDMSCs. Genetic modification of BMDMSCs increased ALP secretion with AdBMP-2 homodimer having the greatest effect in both human and equine cells compared to AdBMP 7 or AdBMP 2/7. BMP protein elution rates reached their maximal concentration between day 4 and 8 and remained relatively stable thereafter, suggesting that genetically modified BMDMSCs could be useful for cell-based delivery of BMPs to a site of bone formation. PMID- 20309954 TI - The vastus lateralis muscle: an anatomical investigation. AB - Anterior knee pain or patellofemoral pain syndrome is commonly encountered by clinicians, but the pathogenesis of this condition is not well understood. While much research has centred around the relationship between vastus medialis and anterior knee pain, little is known about the most lateral of the quadriceps muscle group, vastus lateralis (VL). Knowledge of the anatomical organization of VL is not only necessary to understand its precise function, but to also assist in the development of clinical and biomechanical models of knee dysfunction. The purpose of this study was to investigate the detailed morphology of VL, specifically to provide data relating to architecture, attachment sites, innervation, and the presence of anatomical partitioning within the muscle. The VL muscle was examined in 10 cadaveric lower limbs using macrodissection techniques. On the basis of architecture and innervation, this muscle comprised four partitions with each receiving its own unique nerve branch. The mean fascicular length of VL was 7 cm and the mean fascicular and muscle physiological cross-sectional areas were 1.2 cm(2) and 21.6 cm(2), respectively. In addition to inserting proximally at the base of the greater trochanter and distally into the superolateral border and base of the patella, three additional attachment sites were identified: the lateral intermuscular septum, iliotibial band, and the rectus tendon. The results of this study suggest that the gross morphology of VL is more complex than previously described, and the information provided regarding architecture will contribute to knowledge regarding the function of VL as well as its role in knee joint dysfunction. PMID- 20309955 TI - Intraarticular gene transfer of thrombospondin-1 suppresses the disease progression of experimental osteoarthritis. AB - In osteoarthritis, angiogenesis, which occurs in the osteochondral junction and synovium, may accelerate inflammation and contribute to the severity of the disease. We used anterior cruciate ligament-transection (ACLT) to investigate the therapeutic effect of an angiogenesis inhibitor, thrombospondin-1 (TSP-1), in a rat model of osteoarthritis. Osteoarthritis was induced in Wistar rats in the knee of one hind leg. After ACLT, AdTSP-1 (adenoviral vector encoding mouse TSP 1) was intraarticularly injected into the knee joints. Transgene expression, angiogenesis, and inflammatory responses in the knee joints were examined. They were also assessed morphologically, radiographically, and histologically for manifestations of disease. The levels of TSP-1 peaked on day 3 and were substantially maintained for at least 9 days after AdTSP-1 infection. Adenovirus mediated gene expression was detected in the synovial membrane and chondrocytes. TSP-1 gene transfer induced transforming growth factor-beta (TGF-beta) production, but it reduced microvessel density, macrophage infiltration, and interleukin-1beta (IL-1beta) levels. Gross morphological and histopathological examinations revealed that rats treated with AdTSP-1 had less severe osteoarthritis than controls. In vivo adenovirus-mediated TSP-1 gene transfer significantly reduced microvessel density, inflammation, and suppressed the progression of osteoarthritis. This study provides potential applications of TSP 1 gene delivery for treating osteoarthritis. PMID- 20309956 TI - A functional model of the digital extensor mechanism: demonstrating biomechanics with hair bands. AB - The action of muscles about joints can be explained through analysis of their spatial relationship. A functional model of these relationships can be valuable in learning and understanding the muscular action about a joint. A model can be particularly helpful when examining complex actions across multiple joints such as in the digital extensor mechanism of the hand. A functional model using two hair bands representing the components of the digital extensor mechanism is described. Through superimposition of the model over one's digit, the combined actions of metacarpophalangeal joint flexion and interphalangeal joint extension are clearly demonstrated. The model provides a conceptual demonstration to enhance understanding of this unique combination of muscle actions about multiple joints. PMID- 20309957 TI - Effect of varying osmotic conditions on the response of bovine nucleus pulposus cells to growth factors and the activation of the ERK and Akt pathways. AB - Intervertebral disc and especially nucleus pulposus is characterized by low cellularity. Additionally, extreme variations in osmolality are observed in this tissue, as a result of its specific physicochemical environment, daily activities, or degeneration. In this study, we investigated the role of osmotic fluctuations in the proliferative response of nucleus pulposus cells to exogenous growth factors. In particular, we examined the effect of platelet-derived growth factor (PDGF) and insulin-like growth factor-I (IGF-I) on the proliferation of bovine nucleus pulposus cells and on the activation of the MEK/ERK and PI-3-K/Akt pathways under varying osmotic conditions, in an effort to understand the mechanisms regulating cell proliferation in the intact and the degenerated intervertebral disc. Exposure of cells to high osmolality restrained novel DNA synthesis induced by PDGF or IGF-I in a dose-dependent manner and reduced ERK and Akt activation stimulated by serum or isolated growth factors. Our findings indicate that hyperosmolality imposes a strict control in intervertebral disc cells' proliferation, while hypo-osmotic conditions prevailing in degenerated discs may offer a more permissive environment for cellular proliferation. PMID- 20309958 TI - Evaluation of bone tunnel placement for suture augmentation of an injured anterior cruciate ligament: effects on joint stability in a goat model. AB - Use of novel tissue engineering approaches to heal an injured anterior cruciate ligament (ACL) requires suture repair and/or augmentation to provide joint stability. We evaluated the effects of the location of suture augmentation at the femur and tibia in terms of joint stability using a goat model. Eight goat stifle joints were tested with augmentation sutures placed in two femoral tunnel locations: (1) anterior to, or (2) through the ACL footprint, and two tibial tunnel locations: (1) medial to, or (2) medial and lateral to the footprint. Using a robotic/universal force-moment sensor testing system, the anterior tibial translation (ATT) and the corresponding in situ force carried by the sutures were obtained at 30 degrees , 60 degrees , and 90 degrees of flexion in response to external loads. No significant differences were found between augmentation groups due to tunnel location in terms of ATT or the in situ forces carried by the sutures at all flexion angles tested. Similar results were found under 5 N m of varus-valgus torque. Under a 67 N anterior tibial load, the ATT was restored to within 3 mm of the intact joint following suture augmentation (p > 0.05). Suture augmentation, when placed close to the ACL insertion, could be helpful in providing initial joint stability to aid ACL healing in the goat model. PMID- 20309960 TI - Human cardiospheres are a source of stem cells with cardiomyogenic potential. PMID- 20309961 TI - Law, ethics, religion, and clinical translation in the 21st century--A discussion with Pete Coffey. PMID- 20309962 TI - Intratumoral hypoxic gradient drives stem cells distribution and MGMT expression in glioblastoma. AB - Glioblastoma multiforme (GBM) are highly proliferative tumors currently treated by surgical removal, followed by radiotherapy and chemotherapy, which are counteracted by intratumoral hypoxia. Here we exploited image guided surgery to sample multiple intratumoral areas to define potential cellular heterogeneity in correlation to the oxygen tension gradient within the GBM mass. Our results indicate that more immature cells are localized in the inner core and in the intermediate layer of the tumor mass, whereas more committed cells, expressing glial fibrillary acidic protein and beta-III-tubulin, are distributed along the peripheral and neo-vascularized area, where Smad1/5/8 and Stat3 result to be activated. Moreover, GBM stem cells, identified with the stem cell marker CD133, express high level of DNA repair protein O6-methylguanine-DNA-methyltransferase (MGMT) known to be involved in chemotherapy resistance and highly expressed in the inner core of the tumor mass. Importantly, these cells and, particularly, CD133(+) cells result to be resistant to temozolomide (TMZ), the most used oral alkylating agent for the treatment of GBM, which specifically causes apoptosis only in GBM cells derived from the peripheral layer of the tumor mass. These results indicate a correlation between the intratumoral hypoxic gradient, the tumor cell phenotype, and the tumor resistance to chemotherapy leading to a novel concentric model of tumor stem cell niche, which may be useful to define the real localization of the chemoresistant GBM tumor cells in order to design more effective treatment strategies. PMID- 20309964 TI - Molecular template assisted growth of ultrathin silicon carbide nanowires with strong green light emission and excellent field-emission properties. AB - A novel molecule template assisted chemical co-reduction method has been successfully developed for the controlled synthesis of ultrathin beta-SiC single crystalline nanowires on a large scale. The ultrathin beta-SiC single-crystalline nanowires are about 8 nm in diameter and 200-800 nm in length. The resulting thin beta-SiC single-crystalline nanowire is new in the family of beta-SiC one dimensional (1D) nanostructures. A synergistic action of pi-stacking and steric hindrance result from the 1,10-phenanthroline molecule template are proposed to explain the growth mechanism of the ultrathin beta-SiC single-crystalline nanowires based on the experimental observation. Importantly, such ultrathin beta SiC nanowire has shown a strong structure-induced enhancement of photoluminescence properties and has exhibited a very strong green light emission, which can be seen by naked eye. Furthermore, the unique beta-SiC ultrathin nanowire structure exhibits a low turn-on field (3.57 V microm(-1)) and a large field-emission current density (20 mA cm(-2)). These results suggest that the ultrathin beta-SiC nanowires can be expected to find promising applications as field emitters and photoelectronic devices. PMID- 20309963 TI - Novel interactors and a role for supervillin in early cytokinesis. AB - Supervillin, the largest member of the villin/gelsolin/flightless family, is a peripheral membrane protein that regulates each step of cell motility, including cell spreading. Most known interactors bind within its amino (N)-terminus. We show here that the supervillin carboxy (C)-terminus can be modeled as supervillin specific loops extending from gelsolin-like repeats plus a villin-like headpiece. We have identified 27 new candidate interactors from yeast two-hybrid screens. The interacting sequences from 12 of these proteins (BUB1, EPLIN/LIMA1, FLNA, HAX1, KIF14, KIFC3, MIF4GD/SLIP1, ODF2/Cenexin, RHAMM, STARD9/KIF16A, Tks5/SH3PXD2A, TNFAIP1) co-localize with and mis-localize EGFP-supervillin in mammalian cells, suggesting associations in vivo. Supervillin-interacting sequences within BUB1, FLNA, HAX1, and MIF4GD also mimic supervillin over expression by inhibiting cell spreading. Most new interactors have known roles in supervillin-associated processes, e.g. cell motility, membrane trafficking, ERK signaling, and matrix invasion; three (KIF14, KIFC3, STARD9/KIF16A) have kinesin motor domains; and five (EPLIN, KIF14, BUB1, ODF2/cenexin, RHAMM) are important for cell division. GST fusions of the supervillin G2-G3 or G4-G6 repeats co sediment KIF14 and EPLIN, respectively, consistent with a direct association. Supervillin depletion leads to increased numbers of bi- and multi-nucleated cells. Cytokinesis failure occurs predominately during early cytokinesis. Supervillin localizes with endogenous myosin II and EPLIN in the cleavage furrow, and overlaps with the oncogenic kinesin, KIF14, at the midbody. We conclude that supervillin, like its interactors, is important for efficient cytokinesis. Our results also suggest that supervillin and its interaction partners coordinate actin and microtubule motor functions throughout the cell cycle. PMID- 20309965 TI - A series of open-framework aluminoborates templated by transition-metal complexes. AB - A series of open-framework aluminoborates (ABOs) [M(dien)(2)][AlB(6)O(11)(OH)] (M=Co (I a), Ni (I b), Cd (I c), Zn (I d); dien=diethylenetriamine) and [M(en)(3)][AlB(7)O(12)(OH)(2)] (H(2)O)(0.25) (M=Co (II a), Ni (II b); en=ethylenediamine) have been made under hydrothermal conditions and characterized by elemental analysis, IR spectroscopy, thermogravimetric analysis, UV/Vis and fluorescence spectroscopy, powder X-ray diffraction, single-crystal X ray diffraction, and nonlinear optical determination. These compounds were classified as two structural types: Type I (I a-d) contains AlO(4) tetrahedra and B(6)O(11)(OH) clusters, which link to form a new 3D framework with 7-/9-ring helical channels and large 13-ring channels; whereas type II (II a,b) is composed of AlO(4) tetrahedra, chainlike B(4)O(6)(OH)(2) tetramer, and crablike B(6)O(12) clusters, which interconnect to form other new 3D frameworks with 8-ring helical channels, rare 16-ring double-helical channels, and larger odd 15-ring channels. These compounds represent the first examples of 3D ABOs templated by transition metal complexes (TMCs). I c,d present good second harmonic generation (SHG) properties. UV/Vis spectral investigation indicates that I a-d and II a,b are wide-band-gap semiconductors. PMID- 20309967 TI - Borohydrides from organic hydrides: reactions of Hantzsch's esters with B(C(6)F(5))(3). AB - We report herein that the reaction between a series of Hantzsch's ester analogues 1 a-d with the Lewis acidic species B(C(6)F(5))(3) results in facile transfer of hydride to boron. The main products of this reaction are pyridinium borohydride salts 2 a-d, which are obtained in high to moderate yields. The N-substituted substrates (N-Me, N-Ph) reacted in high yield 90-98 % and the connectivity of the products were confirmed by an X-ray crystallographic analysis of the N-Me borohydride salt 2 a. Unsubstituted Hanztsch's ester 1 a reacted less effectively generating only 60 % of the corresponding borohydride salt, with the balance of the material sequestered as the ester-bound Lewis acid-base adduct 3 a. Formation of the Lewis acid-base adduct could be minimized by increasing the steric bulk about the ester groups as in 1 d. The connectivity of the carbonyl-bound adduct was confirmed by an X-ray crystallographic analysis of 3 e the product of the reaction of methyl ketone 1 e with B(C(6)F(5))(3). We also explored the generation of these pyridinium salts by employing frustrated Lewis pair methodology. However, the reaction of mixtures of the corresponding pyridine and B(C(6)F(5))(3) with hydrogen gas only resulted in formation of trace amounts of the pyridinium borohydride, along with the Lewis acid-base adduct of the starting material and B(C(6)F(5))(3). The 1,2-dihydropyridine adduct was the final product of this reaction. This was ascribed to the low basicity of the pyridine nitrogen and the complicating formation of an ester bound Lewis acid-base adduct. PMID- 20309966 TI - A triphenylphosphonium-functionalised cyclometalated platinum(II) complex as a nucleolus-specific two-photon molecular dye. AB - An organometallic cyclometalated platinum(II) complex, [Pt(L(3))Cl][PF(6)], has been synthesised from a specially designed cyclometalating ligand, HL(3) (triphenyl{5-[3-(6-phenylpyridin-2-yl)-1H-pyrazol-1-yl]pentyl}phosphonium chloride), that contains a pendant carbon chain carrying a terminal cationic triphenylphosphonium moiety. Aside from its room temperature single-photon luminescent properties in solution, [Pt(L(3))Cl](+) can also produce two-photon induced luminescence at room temperature upon excitation at 700 nm from a mode locked Ti:sapphire laser. Its two-photon absorption cross-section in DMF at room temperature was measured to be 28.0x10(-50) cm(4) s photon(-1). [Pt(L(3))Cl](+) is able to selectively stain the cell nucleolus. This has been demonstrated by two-photon confocal imaging of live and methanol-fixed HeLa (human cervical carcinoma) and 3T3 (mouse skin fibroblasts) cells. This organelle specificity is likely to be related to its special affinity for proteins within cell nucleoli. As a result of such protein affinity, [Pt(L(3))Cl](+) is an efficient RNA transcription inhibitor and shows rather profound cytotoxicity. On the other hand, the organelle-specific labelling and two-photon-induced luminescent properties of [Pt(L(3))Cl](+) renders it a useful nuclear dye for the 3 dimensional reconstruction of optical sections of thick tissues, for example, mouse ileum tissues, by multiphoton confocal microscopy. PMID- 20309969 TI - Effect of bulkiness on reversible substitution reaction at Mn(II) center with concomitant movement of the lattice DMF: observation through single-crystal to single-crystal fashion. AB - The porous coordination polymer ({[Mn(L)H(2)O](H(2)O)(1.5)(dmf)}(n), 1) (DMF=N,N dimethylformamide) exhibits variety of substitution reactions along with movement of lattice DMF molecule depending upon bulkiness of the external guest molecules. If pyridine or 4-picoline is used as a guest, both lattice and coordinated solvent molecules are simultaneously substituted (complexes 6 and 7, respectively). If a bulky guest like aniline is used, a partial substitution at the metal centers and full substitution at the channels takes place (complex 8). If the guest is 2-picoline (by varying the position of bulky methyl group with respect to donor N atom), one Mn(II) center is substituted by 2-picoline, whereas the remaining center is substituted by a DMF molecule that migrates from the channel to the metal center (complex 9). Here, the lattice solvent molecules are substituted by 2-picoline molecules. For the case of other bulky guests like benzonitrile or 2,6-lutidine, both the metal centers are substituted by two DMF molecules, again migrating from the channel, and the lattice solvent molecules are substituted by these guest molecules (complex 10 and 11, respectively). A preferential substitution of pyridine over benzonitrile (complex 12) at the metal centers is observed only when the molar ratio of PhCN:Py is 95:5 or less. For the case of an aliphatic dimethylaminoacetonitrile guest, the metal centers remain unsubstituted (complex 13); rather substitutions of the lattice solvents by the guest molecules take place. All these phenomena are observed through single crystal to single crystal (SC-SC) phenomena. PMID- 20309968 TI - A colorimetric sensor array for the detection of the date-rape drug gamma hydroxybutyric acid (GHB): a supramolecular approach. AB - gamma-Hydroxybutyric acid (GHB), a colourless, odourless and tasteless chemical, has become one of the most dangerous illicit drugs of abuse today. At low doses, this drug is a central nervous system depressant that reduces anxiety and produces euphoria and relaxation, sedating the recipient. There is an urgent need for simple, easy-to-use sensors for GHB in solution. Here, we present a colorimetric sensor array based on supramolecular host-guest complexes of fluorescent dyes with organic capsules (cucurbiturils) for the detection of GHB. PMID- 20309970 TI - Luminescence tuning of upconversion nanocrystals. AB - Upconversion luminescence tuning of beta-NaYF(4) nanorods under 980 nm excitation has successfully been achieved by tridoping with Ln(3+) ions with different electronic structures. The effects of Ce(3+) ions on NaYF(4):Yb(3+)/Ho(3+) as well as Gd(3+) ions on NaYF(4):Yb(3+)/Tm(3+)(Er(3+)) have been studied in detail. By tridoping with Ce(3+) ions, not only were unusual (5)G(5)-->(5)I(7) and (5)F(2)/(3)K(8)-->(5)I(8) transitions from Ho(3+) ions and 5d-->4f transitions from Ce(3+) ions observed in NaYF(4):Yb(3+)/Ho(3+) nanorods, but also an increase in the intensity of (5)F(5)-->(5)I(8) relative to (5)S(2)/(5)F(4)-->(5)I(8) with increasing Ce(3+) concentration, which can be attributed to efficient energy transfers of (5)I(6) (Ho)+(2)F(5/2) (Ce)-->(5)I(7) (Ho)+(2)F(7/2) (Ce) and (5)S(2)/(5)F(4) (Ho)+(2)F(5/2) (Ce)-->(5)F(5) (Ho)+(2)F(7/2) (Ce). Interestingly, with increasing pump power density, the luminescence of NaYF(4):Yb(3+)/Ho(3+) nanorods is always dominated by the (5)S(2)/(5)F(4)-->(5)I(8) transition, whereas the luminescence of Ce(3+)-tridoped NaYF(4):Yb(3+)/Ho(3+) nanorods is dominated by the (5)S(2)/(5)F(4)-->(5)I(8) and (5)G(5)-->(5)I(7) transitions in turn. These observations are discussed on the basis of a rate equation model. Furthermore, Gd(3+)-tridoped NaYF(4):Yb(3+)/Tm(3+)(Er(3+)) nanorods can emit multicolor upconversion emissions spanning from the UV to the near-infrared under 980 nm excitation. (6)P(5/2)-->(8)S(7/2) ( approximately 306 nm) and (6)P(7/2)- >(8)S(7/2) ( approximately 311 nm) transitions from Gd(3+) ions were observed. In addition to the aforementioned luminescence properties, these Gd(3+)-tridoped nanorods also exhibit paramagnetic behavior at room temperature and superparamagnetic behavior at 2 or 5 K. PMID- 20309971 TI - BF3.OEt2-catalyzed intermolecular reactions of vinylidenecyclopropanes with bis(p alkoxyphenyl)methanols: a novel cationic 1,4-aryl-migration process. AB - BF(3)OEt(2)-catalyzed reactions of vinylidenecyclopropanes (VDCPs) 1 with bis(aryl)methanols 2 were thoroughly investigated. When VDCPs 1 reacted with electron-rich bis(aryl)methanols 2, diastereomeric rotamers of indene derivatives formed in excellent yields by a novel cationic 1,4-aryl migration between two carbon atoms and the subsequent intramolecular Friedel-Crafts reaction pathways in the presence of BF(3).OEt(2) under mild conditions. As for electron-deficient or less-electron-rich bis(aryl)methanols 2, either trialkene products formed in good yields by direct deprotonation, or another type of indene derivative was produced by direct intramolecular Friedel-Crafts reaction, depending on the substituents on the cyclopropane of VDCPs. In addition, DFT calculations were carried out to explain the experimental results. Plausible mechanisms for all these transformations are proposed on the basis of the experimental and computational results. PMID- 20309972 TI - Nano- and microstructure fabrication by using a three-component system. AB - Two-component amphiphiles based on hydrogen-bonded complexes between terephthaloylbisalanine (H(2)TBA) and dodecylamine (DA) are able to self-assemble into nano- and microsized superstructures in an aqueous solvent. It is possible to modulate the morphology of these self-assembled superstructures by modifying the composition of the complexes, which can be achieved by changing the molar ratio of the two components or by changing the chirality of H(2)TBA. For example, right-handed microhelical ribbon structures were formed with L-TBA(1.0)DA(2.0), whereas in the case of rac-TBA(1.0)DA(2.0), flat ribbonlike structures were observed. Although L-TBA(1.0)DA(1.0) exhibited entangled fibrous structures, rac TBA(1.0)DA(1.0) exhibited wire structures. Different ratios of H(2)TBA and DA were self-assembled into fiber-, wire-, and tubulelike superstructures, as well as monoclinic, columnar, and lamellar aggregation patterns. The self-assembled superstructures of TBA(x)DA(y) were significantly changed by adding metal ions. Transition metal (Cd(II), Co(II), and Zn(II)) complexes with L-TBA(x)DA(y) self assembled into rod-, tubule-, wire-, and platelike superstructures. Metal-ion complexes with rac-TBA(x)DA(y) exhibited different superstructures. Our work suggests that it is possible to fabricate a wide variety of nano- and microsized superstructures by using two- and three-component amphiphiles. PMID- 20309973 TI - New fluorinated rhodamines for optical microscopy and nanoscopy. AB - New photostable rhodamine dyes represented by the compounds 1 a-r and 3-5 are proposed as efficient fluorescent markers with unique combination of structural features. Unlike rhodamines with monoalkylated nitrogen atoms, N',N-bis(2,2,2 trifluoroethyl) derivatives 1 e, 1 i, 1 j, 3-H and 5 were found to undergo sulfonation of the xanthene fragment at the positions 4' and 5'. Two fluorine atoms were introduced into the positions 2' and 7' of the 3',6'-diaminoxanthene fragment in compounds 1 a-d, 1 i-l and 1 m-r. The new rhodamine dyes may be excited with lambda=488 or 514 nm light; most of them emit light at lambda=512 554 nm (compounds 1 q and 1r at lambda=576 and 589 nm in methanol, respectively) and have high fluorescence quantum yields in solution (up to 98 %), relatively long excited-state lifetimes (>3 ns) and are resistant against photobleaching, especially at high laser intensities, as is usually applied in confocal microscopy. Sulfonation of the xanthene fragment with 30 % SO3 in H2SO4 is compatible with the secondary amide bond (rhodamine-CON(Me)CH2CH2COOH) formed with MeNHCH2CH2COOCH3 to providing the sterically unhindered carboxylic group required for further (bio)conjugation reactions. After creating the amino reactive sites, the modified derivatives may be used as fluorescent markers and labels for (bio)molecules in optical microscopy and nanoscopy with very-high light intensities. Further, the new rhodamine dyes are able to pass the plasma membrane of living cells, introducing them as potential labels for recent live cell-tag approaches. We exemplify the excellent performance of the fluorinated rhodamines in optical microscopy by fluorescence correlation spectroscopy (FCS) and stimulated emission depletion (STED) nanoscopy experiments. PMID- 20309974 TI - Evolution of a constitutional dynamic library driven by self-organisation of a helically folded molecular strand. AB - Conversion of macrocyclic imine entities into helical strands was achieved through three- and four-component exchange reactions within constitutionally dynamic libraries. The generation of sequences of the intrinsic helicity codon, based on the hydrazone-pyrimidine fragment obtained by condensation of pyrimidine dialdehyde A with pyrimidine bis-hydrazine B, shifted the equilibrium between all the possible macrocycles and strands towards the full expression (>98%) of helical product [A/B]. Furthermore, it was shown that chain folding accelerated the dynamic exchange reactions among the library members. Lastly, in four component experiments (involving A, B, E and either C or D), even though the macrocyclic entities ([A/C], [B/E]; [A/D], [B/E]) were the kinetically preferred products, over time dialdehyde A relinquished its initial diamine partners C or D to opt for bis-hydrazine B, which allowed the preferential formation of the helically folded strand. The present results indicate that self-organisation pressure was able to drive the dynamic system towards the selective generation of the strand undergoing helical folding. PMID- 20309975 TI - A 4-hydroxypyrrolidine-catalyzed mannich reaction of aldehydes: control of anti selectivity by hydrogen bonding assisted by Bronsted acids. AB - An anti-selective Mannich reaction of aldehydes with N-sulfonyl imines has been developed by using a 4-hydroxypyrrolidine in combination with an external Bronsted acid. The catalyst design is based on three elements: the alpha substituent of the pyrrolidine, the 4-hydroxy group, and the Bronsted acid, the combination of which is essential for high chemical and stereochemical efficiency. The reaction works with aromatic aldehyde-derived imines, which have rarely been employed in previously reported enamine-based anti-Mannich reactions. Additionally, both N-tosyl and N-nosyl imines can be successfully used and the Mannich adducts can be easily reduced or oxidized, and after N-deprotection the corresponding beta-amino acids and beta-amino alcohols can be obtained with good yields. The results also show that this ternary catalytic system may be practical in other enamine-based reactions. PMID- 20309976 TI - Phthalocyanine-polyamine conjugates as pH-controlled photosensitizers for photodynamic therapy. AB - A series of aryl hydroxyamines prepared by reductive amination were treated with silicon(IV) phthalocyanine dichloride in the presence of pyridine to give the diaxially substituted phthalocyanine-polyamine conjugates 1-5. The electronic absorption, fluorescence emission, and efficiency at generating reactive oxygen species of these compounds were all sensitive to the pH environment. Under acidic conditions, the fluorescence quantum yields and the singlet oxygen quantum yields of these compounds were greatly enhanced in DMF as a result of protonation of the amino moieties, which inhibited the photoinduced electron-transfer deactivation pathway. The Q band was diminished and broadened, and the fluorescence intensity decreased as the pH increased in citrate buffer solutions. The rate of superoxide radical formation was also reduced in a higher pH environment. Compound 3, containing a terminal 4-chlorophenyl group at the axial substituent, showed the most desirable pH-responsive properties, which makes it a promising tumor selective fluorescence probe and photosensitizer for photodynamic therapy. All of the phthalocyanines 1-5 were highly photocytotoxic against HT29 and HepG2 cells with IC(50) values as low as 0.03 microM. Compound 3 was highly selective toward lysosomes, but not mitochondria of HT29 cells. PMID- 20309977 TI - Gold-catalyzed dealkoxylative carbocyclization/[3+3] annulation cascade of acetal allene or ketal-allene substrates. PMID- 20309978 TI - A convenient synthesis of benzonitriles via electrophilic cyanation with N cyanobenzimidazole. PMID- 20309979 TI - Catalytic asymmetric mannich-ketalization reaction: highly enantioselective synthesis of aminobenzopyrans. PMID- 20309980 TI - Catalytic asymmetric domino Michael-Henry reaction: enantioselective access to bicycles with consecutive quaternary centers by using bifunctional catalysts. PMID- 20309981 TI - Chemoenzymatic dynamic kinetic resolution of axially chiral allenes. AB - At the palladium: Dimeric palladium bromide complexes bearing monodentate N heterocyclic carbene ligands have been identified as efficient catalysts for the chemoselective racemization of axially chiral allenyl alcohols. In combination with porcine pancreatic lipase as biocatalyst, a dynamic kinetic resolution has been developed, giving access to optically active allenes in good yield and high enantiomeric purity (see scheme). PMID- 20309982 TI - Synthetic design of heterometallic cluster compounds with site-selective and stepwise substitution of bridging carboxylates. AB - At the right places: Owing to substitution-lability difference in disparate metal centers, an oxo-centered heterometallic trinuclear acetato complex [Ru2MgO(CH3COO)6(py)3] (py = pyridine; see picture) undergoes site-selective substitution of propionates and ferrocenycarboxylates in a stepwise manner. The new substituted families have been successfully separated by chromatography and fully characterized. PMID- 20309983 TI - Identification of hot regions of the Abeta-IAPP interaction interface as high affinity binding sites in both cross- and self-association. PMID- 20309984 TI - A facile method to encapsulate proteins in silica nanoparticles: encapsulated green fluorescent protein as a robust fluorescence probe. PMID- 20309985 TI - Poly(vinyl ketone)s by controlled boron group transfer polymerization (BGTP). PMID- 20309986 TI - Dipeptide crystals as excellent permselective materials: sequential exclusion of argon, nitrogen, and oxygen. PMID- 20309987 TI - Structurally and stereochemically diverse tetrahydropyran synthesis through oxidative C-H bond activation. PMID- 20309988 TI - A concise total synthesis of (+)-neopeltolide. PMID- 20309989 TI - Photochemical control of reversible encapsulation. PMID- 20309990 TI - The prenatal origins of lung cancer. I. The fetus. AB - People differ in their susceptibility to developing cancer on exposure to carcinogens such as tobacco. What causes this is largely unknown. One possibility is that it is determined by nutritional influences during development that permanently change the structure and function of the baby's body. We studied an older and a younger cohort, totaling 20,431 men and women, born in Helsinki during 1924-1933 and 1934-1944. Their body size at birth had been recorded. Of them, 385 had developed lung cancer. Smoking history was known for 6,822 people. At birth, babies who later developed lung cancer had a high ponderal index (birthweight/length(3)). This association was confined to people whose mother's height was below the median. Among these people in the older cohort, the hazard ratio associated with a ponderal index >30 kg/m(3) was 3.1 (95% CI 1.6-5.9), in comparison to those with a ponderal index of 26 kg/m(3) or less (P for trend < 0.001). The equivalent figures for the younger cohort were 2.9 (1.2-7.0, P for trend = 0.001) and this association was independent of smoking. We suggest that a high ponderal index in babies born to short mothers is the result of low amino acid delivery to the fetus in relation to glucose delivery. We hypothesize that this impairs the development of the babies' antioxidant systems and makes them vulnerable to oxidative stress in later life. This is the first evidence that fetal programming may determine vulnerability to carcinogens in humans. PMID- 20309991 TI - Physical and psychological health of first and second generation Turkish immigrants in Germany. AB - Recent studies in Germany suggest that first generation Turkish immigrants have lower mortality rates compared to native Germans. Conversely, studies examining morbidity, though not national in scope, have demonstrated that first generation Turks may have poorer health than native Germans. Additionally, little is known about the health of the emerging second generation Turkish population in Germany. To evaluate the discrepancy between mortality and morbidity trends and contribute to a better understanding of second generation Turkish immigrant health, this paper uses a nationally-representative dataset, including the 2005 German Gender and Generations Study (GGS) (n = 10,017) and the 2006 GGS Turkish supplement (n = 4,045), to assess three health outcomes: chronic illness, self-assessed health, and feelings of emptiness. The paper investigates whether sex, age, socioeconomic status, emotional support, or duration of residence in Germany predict these dimensions of health. Results establish clear health status differences between Turks and native Germans. Surprisingly, both first and second generation Turks tend to have lower chronic illness rates and rate their health as better than Germans at younger ages, but the advantage diminishes among higher age strata for the first generation. Feelings of emptiness results generally indicate an increased susceptibility to psychological problems for both generations of Turks. Controlling for socioeconomic status and age reduces these health differences modestly, pointing to their likely role as mediators. The relatively higher risks for all three health outcomes among Turkish females of both generations compared to their German counterparts suggest that female Turkish immigrants and their female offspring may be particularly vulnerable. PMID- 20309992 TI - The prenatal origins of lung cancer. II. The placenta. AB - We have shown that people who were short at birth in relation to their weight are at increased risk of lung cancer. We suggested that this reflected low amino acid high glucose delivery to the fetus and that this impaired the development of its antioxidant systems and made it vulnerable to tobacco smoke and other carcinogens in later life. Transfer of amino acids and glucose from mother to fetus depends on the placenta. We here examine how maternal and placental size are related to lung cancer. We studied two cohorts, totaling 20,431 people, born in Helsinki during 1924-1944. Their body size at birth and maternal body size had been recorded together with the weight of the placenta and two diameters of its surface. Of them, 385 had developed lung cancer. Three different maternal placental-fetal phenotypes were associated with lung cancer. Common to each was a short mother and a newborn baby that was short in relation to its weight. Lung cancer was associated with either a small or a large placental surface area. In the three phenotypes, the hazard ratios associated with a 100 cm(2) increase in placental surface were 0.36 (95% CI 0.14 to 0.87, P = 0.02), 2.31 (1.45 to 3.69, P < 0.001) and 2.04 (1.08 to 3.86, P = 0.03). We conclude that three different maternal-placental phenotypes were associated with later lung cancer. We suggest that each led to low amino acid-normal glucose transfer to the fetus, reflected in a newborn baby that was short in relation to its weight. PMID- 20309993 TI - Enumeration of the absolute CD4 T-lymphocyte count by cell-bead assay. AB - BACKGROUND: We have previously developed an alternative approach for undertaking absolute cell counting based upon flow-rate calibration using cell bead (FCB), in which cell bead (CB) can be used as a flow-rate calibration material for generating the absolute microparticle counts. Here, we extended our work of counting CD4+ T-lymphocytes in HIV-infected blood samples with the FCB method. METHODS: CD4+ T-lymphocyte counts in EDTA blood samples from 30 healthy subjects and 80 HIV-1-infected patients were determined using TriTEST reagent. The absolute CD4+ T-lymphocytes were measured by FCB, and the results were compared with the absolute counting by commercial latex bead (CLB) or with flow rate-based calibration method (FR). Statistical correlation and agreement were analyzed using linear regression and Bland-Altman analysis. RESULTS: There was no significant difference in the absolute number of CD4+ T-lymphocyte counts enumerated by FCB when compared with those two reference methods (CLB and FR). The absolute CD4+ T-lymphocyte counts obtained from FCB method was highly correlated with those obtained from CLB [r(2)= 0.99, y = 1.04x - 12.37, P < 0.001, and mean bias 11.96 cell/microl, limit of agreement (LOA) -57.82 - 81.74 cell/microl], FR method (r(2) = 0.98; y = 0.97x - 3.13, P < 0.001, and mean bias 24.15 cell/microl, LOA -114.44 - 66.13 cell/microl). CONCLUSIONS: The use of FCB is comparable with the use of CLB and FR. This approach showed the effective in reducing cost for generating the absolute CD4+ T-lymphocyte counts. Such an approach should facilitate and ensure the success of the ongoing antiretroviral therapy program in resource-limited countries. PMID- 20309994 TI - Field performance of Lynfield and McPhail traps for monitoring male and female sterile Bactrocera tryoni (Froggatt) and wild Dacus newmani (Perkins). AB - BACKGROUND: McPhail traps, baited with protein food lure, are used worldwide for surveillance of many species of fruit flies. Queensland fruit fly (Qfly) Bactrocera tryoni (Froggatt) (Diptera: Tephritidae) is a native Australian fruit fly and normally monitored using Lynfield traps baited with cuelure. On some occasions, McPhail traps with wet food lures are deployed to detect female flies or to find the incursion epicentre. This paper reviews field results on the merits of Lynfield and McPhail traps for detection of male and female Qfly. RESULTS: Following release of equal numbers of sterile males and females, Lynfield traps baited with cuelure captured more Qfly males than protein autolysate or orange concentrate in McPhail traps. Significantly more male than female Qfly were captured in McPhail traps baited with protein autolysate or orange. There was no significant difference between orange concentrate lure and protein autolysate lure in attracting either males or females. Another Australian native fruit fly, Dacus newmani (Perkins), was attracted to cuelure in Lynfield traps but not to either lure in McPhail traps. CONCLUSIONS: The data obtained run counter to the reputation of McPhail traps baited with protein autolysate or orange concentrate as a specialist lure/trap combination for female Qfly. PMID- 20309995 TI - Monitoring for imidacloprid resistance in the tobacco-adapted form of the green peach aphid, Myzus persicae (Sulzer) (Hemiptera: Aphididae), in the eastern United States. AB - BACKGROUND: Imidacloprid is the primary insecticide for controlling the tobacco adapted form of the green peach aphid (TGPA), Myzus persicae (Sulzer), a major pest of tobacco worldwide. This study used leaf-dip bioassays to assess TGPA resistance to imidacloprid in the eastern United States from 2004 through 2007. RESULTS: When combined over the 4 year study, 18, 14 and 3% of the TGPA had imidacloprid resistance ratios (RRs) of 10-20-fold, 20-30-fold and 30-90-fold, respectively, compared with the most susceptible colony tested. This indicates that some colonies have developed moderate levels of resistance to imidacloprid. A colony collected near Clayton, North Carolina, had the highest RR of 91 (LC(50) value = 31 mg L(-1)). This resistance declined for six tests over a 3 year period in the laboratory culture from >130-fold RR (LC(50) = 48 mg L(-1)) to 40-fold RR (LC(50) = 15 mg L(-1)). Over the same period, the most susceptible colony and a standard colony not exposed to imidacloprid for over 7 years had consistently low LC(50) values. CONCLUSION: Moderate levels of resistance to imidacloprid are noticed among TGPA colonies from the eastern United States. The variation in resistance indicates that the factors responsible are present in the populations at low frequencies and are just not enough to cause field failures yet. PMID- 20309996 TI - Near future ocean acidification increases growth rate of the lecithotrophic larvae and juveniles of the sea star Crossaster papposus. AB - Ocean acidification (OA) is believed to be a major threat for near-future marine ecosystems, and that the most sensitive organisms will be calcifying organisms and the free-living larval stages produced by most benthic marine species. In this respect, echinoderms are one of the taxa most at risk. Earlier research on the impact of near-future OA on echinoderm larval stages showed negative effects, such as a decreased growth rate, increased mortality, and developmental abnormalities. However, all the long-term studies were performed on planktotrophic larvae while alternative life-history strategies, such as nonfeeding lecithotrophy, were largely ignored. Here, we show that lecithotrophic echinoderm larvae and juveniles are positively impacted by ocean acidification. When cultured at low pH, larvae and juveniles of the sea star Crossaster papposus grow faster with no visible affects on survival or skeletogenesis. This suggests that in future oceans, lecithotrophic species may be better adapted to deal with the threat of OA compared with planktotrophic ones with potentially important consequences at the ecosystem level. For example, an increase in populations of the top predator C. papposus will likely have huge consequences for community structure. Our results also highlight the importance of taking varying life history strategies into account when assessing the impacts of climate change, an approach that also provides insight into understanding the evolution of life history strategies. PMID- 20309997 TI - In reference to An easy technique to prevent post-tympanoplasty ventilation tube blockage. PMID- 20309998 TI - Opportunities and challenges of rural practice: managing self amid ambiguity. AB - Living and practicing psychology in a small, rural community has opportunities and challenges. We describe the context of rural communities and identify several of those challenges and opportunities. A case study demonstrates the influence of multigenerational involvement, complex professional and social situations, and the potential difficulties facing the responsible clinician. We suggest both a theoretical perspective and specific procedures for treating prototypical cases in a rural practice. PMID- 20310000 TI - Upfront use of gemtuzumab ozogamicin in young children with CD33-positive AML. AB - Gemtuzumab ozogamicin (GO) is a humanized anti-CD33 antibody used for treating patients with CD33+ acute myeloid leukemia (AML). We report three young children (two infants and one toddler) with AML treated with GO 9 mg/m(2). Two received two doses at diagnosis alone with conventional chemotherapy and one received one dose after relapse. GO was well tolerated and all three achieved remission. All were transplanted: one relapsed after 5 months and died of disease, one died a toxic death in remission due to pulmonary fibrosis, and one survived (41 months from diagnosis). In conclusion, GO was well tolerated in these young patients with evidence for efficacy. PMID- 20309999 TI - Restoration of motor inhibition through an abnormal premotor-motor connection in dystonia. AB - To clarify the rationale for using rTMS of dorsal premotor cortex (PMd) to treat dystonia, we examined how the motor system reacts to an inhibitory form of rTMS applied to the PMd in healthy subjects and in a group of patients with focal hand dystonia and DYT1 gene carriers. Continuous theta burst transcranial magnetic stimulation (cTBS) with 300 and 600 pulses (cTBS300 and cTBS600) was applied to PMd, and its after-effects were quantified by measuring the amplitude of MEPs evoked by single pulse transcranial magnetic stimulation (TMS) over the primary motor cortex (M1), short interval intracortical inhibition/facilitation (SICI/ICF) within M1, the third phase of spinal reciprocal inhibition (RI), and writing tests. In addition, in DYT1 gene carriers, the effects of cTBS300 over M1 and PMd on MEPs were studied in separate experiments. In healthy subjects, cTBS300 and cTBS600 over PMd suppressed MEPs for 30 min or more and cTBS600 decreased SICI and RI. In contrast, neither form of cTBS over PMd had any significant effect on MEPs, while cTBS600 increased effectiveness of SICI and RI and improved writing in patients with writer's cramp. NMDYT1 had a normal response to cTBS300 over left PMd. We suggest that the reduced PMd to M1 interaction in dystonic patients is likely to be due to reduced excitability of PMd-M1 connections. The possible therapeutic effects of premotor rTMS may therefore involve indirect effects of PMd on SICI and RI, which this study has shown can be normalised by cTBS. PMID- 20310001 TI - VCR/AraC chemotherapy and ND-CNS-LCH. PMID- 20310002 TI - LINGO1 polymorphisms are associated with essential tremor in Europeans. AB - Essential tremor (ET) is one of the most common movement disorders. Former association studies focussing on candidate genes in ET found a number of risk variants but most of them were not replicated. Recently, a genome-wide association study revealed two intronic sequence variants in the LINGO1 gene associated with ET. Here, we have confirmed association between sequence variants in the LINGO1 gene and the ET phenotype in independent German and French ET samples. The odds ratios for the identified intronic markers rs8030859 (P = 1.0x10(-4)), rs9652490 (P = 9.1x10(-4)), and rs11856808 (P = 3.6x10(-2)) were 1.72 (CI 1.31-2.26), 1.61 (CI 1.21-2.14), and 1.30 (CI 1.02-1.66), respectively, in our German sample. LINGO1 is an interesting candidate gene because it plays a key role in central nervous system biology, is selectively expressed in the nervous system, and is an inhibitor of oligodendrocyte differentiation and neuronal myelination. Our study gives further evidence that LINGO1 acts as a susceptibility gene for ET. PMID- 20310003 TI - Sperm analysis of patients after successful treatment of childhood acute lymphoblastic leukemia with chemotherapy. AB - Survivors of childhood acute lymphoblastic leukemia (ALL) treated with radiotherapy are at risk for impaired fertility. Whether chemotherapy alone is also long-term gonadotoxic is unclear. We assessed gonadal function in 11 male ALL-survivors treated with the same chemotherapy regimen and compared sperm analysis to healthy men. While sex hormone levels were normal in all subjects, 5/11 survivors showed pathological sperm concentration and 4/11 a decreased total sperm count compared to WHO criteria. Compared to healthy controls, all quantitative parameters in semen analysis of survivors were decreased. This suggests that treatment with chemotherapeutic agents alone, even in moderate doses, might have a gonadotoxic effect. PMID- 20310004 TI - Sertoli Leydig cell ovarian tumour and gastric polyps as presenting features of Peutz-Jeghers syndrome. AB - We report a case of Peutz-Jeghers syndrome (PJS) in a 2-year old with precocious puberty secondary to a Sertoli-Leydig cell tumour. Family history of PJS and other neoplasms were discovered. The tumour was excised and the STK11 gene deletion identified in both patient and father. Screening revealed hamartomatous gastric polyps, which were removed. Current recommendations for screening of children with PJS begin at age 8 years, based on reported occurrence of complications 1. This report illustrates the importance of considering early screening, along with close clinical review and patient/parent education, for detection of life threatening neoplasms and complications. PMID- 20310005 TI - Clinicopathologic study of glioblastoma in children with neurofibromatosis type 1. AB - BACKGROUND: Neurofibromatosis type 1 (NF1) is characterized by low-grade tumors of the central and peripheral nervous system. There is also an increased risk of developing malignant tumors. Glioblastoma is an uncommon, malignant tumor of children that is even less frequently observed in children with NF1. PROCEDURE: We performed a retrospective review of patients with NF1 and glioblastoma to determine specific clinical and pathologic indicators of overall prognosis. RESULTS: Five patients were identified from the CHB/DFCI database for whom pathologic and imaging studies were available. All pathologic specimens demonstrated vascular proliferation and necrosis. All samples stained positively for p53. Chromogenic in situ hybridization (CISH) for epidermal growth factor receptor (EGFR) copy numbers was increased, PTEN copy numbers were normal and the promoter of the O(6)-methylguanine-DNA methyltransferase (MGMT) gene was unmethylated in the one patient evaluated. In the same time period, there were 56 patients without NF1 diagnosed with glioblastoma who were treated at our institution. Although the small sample size precludes formal statistical analysis, the 2-year survival of patients with NF1 is 60% with median overall survival of 9.25 years compared to non-NF1 patients with a 2-year survival of 25% and median overall survival 1.08 years. CONCLUSIONS: This study provides preliminary evidence that children with NF1 may be at risk for glioblastoma, but that these patients have an increased survival compared to children without NF1. Additional molecular studies will be required to determine if the pathogenesis of these tumors differs from glioblastoma in children without NF1. PMID- 20310006 TI - MTR polymorphic variant A2756G and retinoblastoma risk in Brazilian children. AB - BACKGROUND: Polymorphisms in the genes of folate and methionine metabolism enzymes have been associated with some forms of cancer by affecting DNA synthesis, repair, and methylation. PROCEDURE: A case-control study of 72 retinoblastoma cases and 98 cancer-free children controls was performed to investigate whether the polymorphisms of the methylenetetrahydrofolate reductase (MTHFR C677T and A1298C), methionine synthase (MTR A2756G), carrier of reduced folate 1 (RFC-1 A80G) and thymidylate synthase (TYMS 2R > 3R) altered the risk for retinoblastoma. RESULTS: MTR A2756G AG plus GG genotype frequencies were higher in patients than in controls (45% vs. 26%, P = 0.03). Individual carriers of the variant allele G had a 2.02 (95% CI: 1.05-3.92)-fold increased risk for retinoblastoma. In contrast, no association was observed with respect to MTHFR C677T and A1298C, RFC A80G, and TYMS polymorphisms. CONCLUSIONS: This study presents evidence for an association between the MTR A2756G polymorphism and retinoblastoma susceptibility in a Northeast population from Brazil. PMID- 20310007 TI - ATP13A2 mutations (PARK9) cause neurodegeneration with brain iron accumulation. AB - Kufor Rakeb disease (KRD, PARK9) is an autosomal recessive extrapyramidal pyramidal syndrome with generalized brain atrophy due to ATP13A2 gene mutations. We report clinical details and investigational results focusing on radiological findings of a genetically-proven KRD case. Clinically, there was early onset levodopa-responsive dystonia-parkinsonism with pyramidal signs and eye movement abnormalities. Brain MRI revealed generalized atrophy and putaminal and caudate iron accumulation bilaterally. Our findings add KRD to the group of syndromes of neurodegeneration with brain iron accumulation (NBIA). KRD should be considered in patients with dystonia-parkinsonism with iron on brain imaging and we suggest classifying as NBIA type 3. PMID- 20310008 TI - Propriospinal myoclonus due to cord compression in the absence of myelopathy. PMID- 20310009 TI - A new rating instrument to assess festination and freezing gait in Parkinsonian patients. AB - Festination and freezing of gait (FOG) are sudden episodic inabilities to initiate or sustain locomotion mostly experienced during the later stages of Parkinson's disease (PD) or other higher-level gait disorders. The aim of this study was to develop a clinical rating instrument for short-interval rating of festination and FOG. Foot movements of 33 patients were video taped and rated during 12 episodes in a standardized course on a four-level interval scale according to severity. Motor blocks were provoked in four situations and by three levels of dual-tasking (tasks). Addition of the item scores produced a FOG score. The assessment requires less than 15 min. The inter-rater and re-test reliability of the FOG score is high (Kendall kappa = 0.85-0.92, P < 0.0001). Variability of the item scale due to situations and tasks can be attributed to unidimensional group factors (Cronbach's alpha 0.84 and 0.94). Group comparisons and a logistic regression model show significant effects for both situations and tasks on the item scale (Friedman test: "situation": P < 0.0001, "task": P < 0.0001). Six patients with PD have significantly different scores during mobile (practical ON; 6.2 +/- 3.9) and immobile (practical OFF; 15.8 +/- 4.6) medication states (P < 0.05). The FOG score correlates with the 10 m number of steps (rho = 0.58; P = 0.001) and with the self-evaluation of FOG (rho = 0.51; P < 0.01). Our results encourage the further use of the FOG score to evaluate festination and FOG. PMID- 20310010 TI - Baclofen-induced chorea in complex regional pain syndrome-related dystonia. PMID- 20310011 TI - 4SC-101, a novel immunosuppressive drug, inhibits IL-17 and attenuates colitis in two murine models of inflammatory bowel disease. AB - BACKGROUND: Dihydroorotate dehydrogenase (DHODH) is a key enzyme involved in pyrimidine biosynthesis. DHODH is a known target for the treatment of autoimmune diseases. 4SC-101 is a novel immunosuppressive drug that inhibits DHODH. A goal of our study was to examine the in vitro effects of 4SC-101 on IL-17 production by mononuclear cells. In addition, we evaluated the efficacy of 4SC-101 against acute TNBS (2,4,6-tritrobenzene sulfonic acid) and chronic dextran sodium sulfate (DSS)-induced colitis in mice. METHODS: Peripheral blood mononuclear cells (PBMCs) from healthy human donors were used to evaluate cellular proliferation and cytokine (IL-17, TNF-alpha) production. The oral effects of 4SC-101 (100 or 200 mg/kg) were examined following induction of chronic colitis by the administration of 3% DSS (4 cycles) to Balb/c mice. Morphometric and histological indices of colitis were evaluated as indicators of drug efficacy. 4SC-101 was also administered for 6 days after the intracolonic administration of TNBS (20 mg in 50% ethanol) to female Balb/c mice. The colons were analyzed for overall macroscopic damage, ulceration, total length, distal segment weight, MPO activity, and histological pathology as indicators for the effectiveness of 4SC 101. RESULTS: In vitro, 4SC-101 is a potent inhibitor of human DHODH, inhibits lymphocyte proliferation, and uniquely blocks phytohemagglutinin-stimulated IL-17 production by lymphocytes. In vivo, oral administration of 4SC-101 effectively improved both chronic DSS and acute TNBS colitis in mice. In these colitis models the overall efficacy profile of 4SC-101 was similar to that of dexamethasone. CONCLUSIONS: 4SC-101 is a novel immunosuppressive drug with excellent potential for the treatment of intestinal inflammation. PMID- 20310012 TI - Bifidobacterium lactis inhibits NF-kappaB in intestinal epithelial cells and prevents acute colitis and colitis-associated colon cancer in mice. AB - BACKGROUND: The aim of this study was to investigate the antiinflammatory effects of Bifidobacterium lactis on intestinal epithelial cells (IECs) and on experimental acute murine colitis and its tumor prevention effects on colitis associated cancer (CAC) in mice. METHODS: Human HT-29 cells were stimulated with IL-1beta, lipopolysaccharides, or tumor necrosis factor-alpha with and without B. lactis, and the effects of B. lactis on nuclear factor kappa B (NF-kappaB) signaling in IEC were examined. For in vivo study, dextran sulfate sodium (DSS) treated mice were fed with and without B. lactis. Finally, we induced colonic tumors in mice by azoxymethane (AOM) and DSS and evaluated the effects of B. lactis on tumor growth. RESULTS: B. lactis significantly suppressed NF-kappaB activation, including NF-kappaB-binding activity and NF-kappaB-dependent reporter gene expression in a dose-dependent manner, and suppressed IkappaB-alpha degradation, which correlated with the downregulation of NF-kappaB-dependent gene products. Moreover, B. lactis suppressed the development of acute colitis in mice. Compared with the DSS group, the severity of DSS-induced colitis as assessed by disease activity index, colon length, and histological score was reduced in the B. lactis-treated group. In the CAC model, the mean number and size of tumors in the B. lactis-treated group were significantly lower than those in the AOM group. CONCLUSIONS: Our data demonstrate that B. lactis inhibits NF kappaB and NF-kappaB-regulated genes in IEC and prevents acute colitis and CAC in mice. These results suggest that B. lactis could be a potential preventive agent for CAC as well as a therapeutic agent for inflammatory bowel disease. PMID- 20310013 TI - Nonfistulizing perianal Crohn's disease: clinical features, epidemiology, and treatment. AB - Nonfistulizing perianal lesions, including ulcerations, strictures, and anal carcinoma, are frequently observed in Crohn's disease. Their clinical course remains poorly known. The management of these lesions is difficult because none of the treatments used is evidence-based. Ulcerations may be symptomatic in up to 85% of patients. Most ulcerations heal spontaneously but may also progress to anal stenosis or fistula/abscess. Topical treatments only improve symptoms, while complete healing can occur in patients with perianal ulcerations receiving infliximab therapy. Half of all patients with anal strictures will require permanent fecal diversion. Dilatation for symptomatic strictures should be performed on a highly selective basis in the absence of active rectal disease in order to avoid infectious complications. Anorectal strictures associated with rectal lesions should first be managed with medical therapy. Skin tags are usually painless and may hide other perianal lesions. Anal cancer is uncommon. Its treatment is similar to that recommended for anal cancer occurring in non Crohn's disease patients. After reviewing the classification, clinical features, and epidemiology of each type of nonfistulizing perianal lesion (ulceration, stricture, skin tags, and anal cancer), we discuss the efficacy of medical treatment and surgery. This review article may help physicians in decision-making when managing potentially disabling lesions. PMID- 20310014 TI - Hiccups associated with non-ergoline dopamine agonists in Parkinson's disease. PMID- 20310015 TI - Mucosal healing in patients with ulcerative colitis during a course of selective leukocytapheresis therapy: a prospective cohort study. AB - BACKGROUND: During active ulcerative colitis (UC), vast numbers of granulocytes, monocytes/macrophages (GM) infiltrate the mucosal tissue and can potentially exacerbate inflammation and injury. Accordingly, we were interested to see if selective depletion of GM by adsorption (GMA) impacts mucosal healing (MH) in UC patients. METHODS: In all, 124 patients with clinically and endoscopically active UC received 5 or 10 GMA sessions at one or two sessions/week. The endoscopic severity of mucosal inflammation at entry and 1 week after the last GMA session were scored as follows: 0 = normal mucosa and inactive disease; 1 = mild inflammation; 2 = moderate inflammation; 3 = severe inflammation. Likewise, a score 0 or 1 at post-GMA course was defined as MH. RESULTS: At entry the endoscopic severity of the mucosal inflammation was 2 in 100 patients (81%) and 3 in 24 patients (19%). Following the course of GMA, 56 patients (45%) achieved clinical remission (normal stool frequency and no rectal bleeding). Thirty-four of these 56 responders achieved MH; 32 (94%) of the 34 patients with MH had an endoscopic score of 2 (moderate inflammation) at entry. The maintained clinical remission rate was significantly higher in the 34 patients who achieved MH as compared with 22 patients who achieved clinical remission without MH (P = 0.0005). CONCLUSIONS: MH is achieved more frequently in patients with moderate than with severe endoscopic severity at entry. Further, patients with MH have a reduced risk of future clinical relapse as compared with patients who achieve remission without MH. PMID- 20310016 TI - Monitoring functional serum antitumor necrosis factor antibody level in Crohn's disease patients who maintained and those who lost response to anti-TNF. AB - BACKGROUND: Infliximab (IFX) is an antitumor necrosis factor (TNF)-alpha antibody used to treat Crohn's disease (CD). However, antibodies to IFX (ATI) emerge, which can impair its efficacy. A fluid-phase enzyme immunoassay (FP-EIA) was established for measuring serum functional IFX (f-IFX) in CD patients receiving maintenance IFX. METHODS: In 31 patients, 16 had maintained response (GI) and 15 had lost response to IFX despite good initial response (GII) were selected. Serum f-IFX was measured just before and immediately after IFX infusion and the values together with CD activity index (CDAI) and C-reactive protein (CRP) were compared. RESULTS: IFX therapy in GI and GII were 1.8 +/- 1.2 years and 2.7 +/- 1.5 years, respectively, while the median dose frequency was 56 days in GI and 29 days in GII. Our FP-EIA for f-IFX showed TNF-alpha binding increasing with the IFX dose, which was suppressed by antibodies to IFX. On the infusion day, CRP and CDAI in GII were significantly higher than in GI, while median trough f-IFX for GI and GII were 4.7 MUg/mL and 6.3 MUg/mL, respectively. The median f-IFX immediately after IFX infusion for GI and GII were 149.5 MUg/mL and 126.3 MUg/mL, respectively (P = 0.0488), and binary logistic regression showed conditional maximum likelihood estimate to be -0.0258 (P = 0.0395), supporting association of low postinfusion f-IFX to the loss of response. CONCLUSIONS: FP-EIA could accurately measure f-IFX. High serum ATI strongly impacted f-IFX levels immediately after an infusion. The postinfusion f-IFX level was associated with clinical response. f-IFX level should be valuable in decision-making to optimize treatment efficacy. PMID- 20310017 TI - Diagnostic work-up of inflammatory bowel disease in children: the role of calprotectin assay. AB - BACKGROUND: Some reports highlight the potential application of fecal calprotectin as a direct biomarker of intestinal inflammation and, therefore, as support in choosing candidates for endoscopy. The value of 100 MUg/g was recently assumed as the best cutoff for this assay. The purpose of this study was to assess the diagnostic precision of the fecal calprotectin assay, compared to histology, as a stool-screening biomarker for inflammatory bowel disease (IBD) among a group of prospectively identified patients referred for recurrent abdominal pain and altered bowel habits. METHODS: Between 1999 and 2007 we prospectively evaluated the calprotectin assay in a cohort of patients with recurrent abdominal pain and altered bowel habits associated or not with other symptoms suggestive of IBD. All patients suspected of IBD, according to Rome and Porto criteria, provided stool specimens for the calprotectin assay and subsequently underwent endoscopic procedures. RESULTS: Compared to histology, the cutoff of 100 MUg/g reached a sensitivity and specificity of 100% and 68%, respectively, and a likelihood ratio (LR) of 3.1. The cutoff value of 160 MUg/g, however, in our series produced the best joint estimate of sensitivity and specificity: 100% and 80%, respectively, with an LR of 5. CONCLUSIONS: In pediatric patients with recurrent abdominal pain and changes in stool habits, a positive calprotectin assay is closely associated with IBD; its systematic employment, therefore, seems to improve the process of endoscopy referral. This test, simple and inexpensive, could be included in the first noninvasive phase of an IBD diagnostic work-up. PMID- 20310018 TI - Extrapolating in vitro metabolic interactions to isolated perfused liver: predictions of metabolic interactions between R-bufuralol, bunitrolol, and debrisoquine. AB - Drug-drug interactions (DDIs) are a great concern to the selection of new drug candidates. While in vitro screening assays for DDI are a routine procedure in preclinical research, their interpretation and relevance for the in vivo situation still represent a major challenge. The objective of the present study was to develop a novel mechanistic modeling approach to quantitatively predict DDI solely based upon in vitro data. The overall strategy consisted of developing a model of the liver with physiological details on three subcompartments: the sinusoidal space, the space of Disse, and the cellular matrix. The substrate and inhibitor concentrations available to the metabolizing enzyme were modeled with respect to time and were used to relate the in vitro inhibition constant (K(i)) to the in vivo situation. The development of the liver model was supported by experimental studies in a stepwise fashion: (i) characterizing the interactions between the three selected drugs (R-bufuralol (BUF), bunitrolol (BUN), and debrisoquine (DBQ)) in microsomal incubations, (ii) modeling DDI based on binary mixtures model for all the possible pairs of interactions (BUF-BUN, BUF-DBQ, BUN DBQ) describing a mutual competitive inhibition between the compounds, (iii) incorporating in the binary mixtures model the related constants determined in vitro for the inhibition, metabolism, transport, and partition coefficients of each compound, and (iv) validating the overall liver model for the prediction of the perfusate kinetics of each drug determined in isolated perfused rat liver (IPRL) for the single and paired compounds. Results from microsomal coincubations showed that competitive inhibition was the mechanism of interactions between all three compounds, as expected since those compounds are all substrates of rat CYP2D2. For each drug, the K(i) values estimated were similar to their K(m) values for CYP2D2 indicative of a competition for the same substrate-binding site. Comparison of the performance between the novel liver physiologically based pharmacokinetic (PBPK) model and published empirical models in simulating the perfusate concentration-time profile was based on the area under the curve (AUC) and the shape of the curve of the perfusate time course. The present liver PBPK model was able to quantitatively predict the metabolic interactions determined during the perfusions of mixtures of BUF-DBQ and BUN-DBQ. However, a lower degree of accuracy was obtained for the mixtures of BUF-BUN, potentially due to some interindividual variability in the relative proportion of CYP2D1 and CYP2D2 isoenzymes, both involved in BUF metabolism. Overall, in this metabolic interaction prediction exercise, the PBPK model clearly showed to be the best predictor of perfusate kinetics compared to more empirical models. The present study demonstrated the potential of the mechanistic liver model to enable predictions of metabolic DDI under in vivo condition solely from in vitro information. PMID- 20310019 TI - Four-year clinical outcome of sirolimus- and paclitaxel-eluting stents compared to bare-metal stents for the percutaneous treatment of stable coronary artery disease. AB - BACKGROUND: There are limited data on the long-term safety and efficacy profile of coronary stent implantation in patients with stable coronary artery disease (CAD) undergoing percutaneous coronary intervention (PCI). OBJECTIVE: We aimed to assess the 4-year clinical outcome in patients who received a bare-metal stent (BMS), sirolimus-eluting stent (SES), or a paclitaxel-eluting stent (PES) for the percutaneous treatment of stable angina in our center during 2000-2005. METHODS: In the study period, a total of 2,449 consecutive patients (BMS = 1,005; SES = 373; and PES = 1071) underwent a PCI as part of three historical PCI-cohorts for stable angina and were routinely followed for the occurrence of major adverse cardiac events (MACE). RESULTS: At 4 years follow-up, 264 BMS patients (26.8%) had a MACE, compared to 75 SES patients (20.9%) and 199 PES patients (23.9%). Multivariate analysis showed that SES and PES were superior to BMS with respect to MACE [hazard ratio (HR) = 0.62, 95% confidence interval (CI): 0.47-0.81; HR = 0.67, 95% CI: 0.55-0.82, respectively]. The occurrence of MACE was significantly lower in the SES and PES population, primarily due to less target-vessel revascularization (TVR) procedures (HR = 0.53, 95% CI: 0.37-0.75; HR = 0.71, 95% CI: 0.62-0.81, respectively). The occurrence of early, late, and very late stent thrombosis was equally rare with each stent type. There were no significant differences between SES and PES on death, myocardial infarction, TVR, and MACE. CONCLUSION: These findings suggest that SES and PES result in decreased TVR procedures and MACE compared to BMS at 4 years follow-up. SES or PES implantation should be the preferred choice over BMS for patients with stable CAD undergoing PCI. PMID- 20310021 TI - Failure of the Amplatzer ductal occluder II: kinking of the aortic retention disk at 24 hours. AB - Since March 2008, the new Amplatzer duct occluder II (ADO II) has been used clinically for PDA closure in Europe. We report an interesting case of a 2(1/2) year-old girl with a 3-mm conical shape PDA (type A PDA) who underwent uneventful implantation of 3/4 ADO II with complete closure by angiography and echocardiographic control at the end of the procedure. To our surprise, echocardiography 24 hr later revealed a moderate secondary shunt due to kinking of the aortic retention disk of the device with the central waist and the pulmonary retention disk still in correct position. The persistent shunt was closed 1 year later in the cath lab with a 9/6 Nit-Occlud device. To our knowledge, this is the first reported late complication directly related to the device. PMID- 20310020 TI - Clinical trial: a novel high-dose 1 g mesalamine suppository (Salofalk) once daily is as efficacious as a 500-mg suppository thrice daily in active ulcerative proctitis. AB - BACKGROUND: Mesalamine suppositories are first-line therapy in active ulcerative proctitis; the standard regime still recommends multiple doses per day. The primary objective of this study was to show the noninferiority of once-daily administration of a novel 1 g mesalamine suppository versus thrice-daily administration of the 0.5 g mesalamine suppository. METHODS: This was a single blind (investigator-blinded), randomized, multicenter, comparative, Phase III clinical trial. Patients with mild to moderately active ulcerative proctitis inserted either one mesalamine 1 g suppository at bedtime or one mesalamine 0.5 g suppository thrice daily over a 6-week period. The primary endpoint was rate of remission (Disease Activity Index below 4). RESULTS: In all, 354 patients were evaluable for safety and per-protocol analysis. The new regimen demonstrated noninferiority: The percentage of patients with remission was 87.9% for the once daily 1 g mesalamine suppository and 90.7% for the thrice-daily 0.5 g mesalamine suppository. Each regimen resulted in prompt cessation of clinical symptoms (e.g., median time to <=3 stools per day (all without blood): 5 days in the 1 g mesalamine once-daily and 7 days in the 0.5 g mesalamine thrice-daily group). Patients preferred applying suppositories once a day. CONCLUSIONS: In active ulcerative proctitis the once-daily administration of a 1 g mesalamine suppository is as effective and safe, yet considerably more convenient, than the standard thrice-daily administration of a 0.5 g mesalamine suppository. PMID- 20310022 TI - Stabilization of lysozyme by benzyl alcohol: surface tension and thermodynamic parameters. AB - The aim of the study was to understand the effect of benzyl alcohol on biological activity, aggregation behavior, denaturant and heat-induced unfolding of lysozyme. Compatibility studies of lysozyme carried out with a number of anti microbial preservatives, indicated benzyl alcohol to be the best suppressor of protein aggregation against heat stress. The effect of this preservative was checked at various pH values ranging from 4.0 to 9.0. In spite of reducing the thermal denaturation temperature (T(m)) at all pH values, benzyl alcohol had a stabilizing effect on lysozyme in terms of retaining the biological activity when the enzyme was incubated at 75 degrees C. The reduction in T(m) with increasing benzyl alcohol concentration was correlated with decreasing surface tension of surrounding medium. A detailed thermodynamic study of lysozyme in the presence of benzyl alcohol was carried out at pH 6.2. Change in Gibb's free energy of thermal unfolding at 25 degrees C was found to remain constant in the presence of benzyl alcohol, indicating no interaction of benzyl alcohol with the native protein at room temperature. Both the enthalpy and entropy change at mid point of thermal unfolding were found to increase in the presence of benzyl alcohol indicating the stabilization of partially unfolded state. PMID- 20310023 TI - Correlating particle hardness with powder compaction performance. AB - Assessing particle mechanical properties of pharmaceutical materials quickly and with little material can be very important to early stages of pharmaceutical research. In this study, a wide range of pharmaceutical materials were studied using atomic force microscopy (AFM) nanoindentation. A significant amount of particle hardness and elastic modulus data were provided. Moreover, powder compact mechanical properties of these materials were investigated in order to build correlation between the particle hardness and powder compaction performance. It was found that the materials with very low or high particle hardness most likely exhibit poor compaction performance while the materials with medium particle hardness usually have good compaction behavior. Additionally, the results from this study enriched Hiestand's special case concept on particle hardness and powder compaction performance. This study suggests that the use of AFM nanoindentation can help to screen mechanical properties of pharmaceutical materials at early development stages of pharmaceutical research. PMID- 20310024 TI - Creation of a tablet database containing several active ingredients and prediction of their pharmaceutical characteristics based on ensemble artificial neural networks. AB - A tablet database containing several active ingredients for a standard tablet formulation was created. Tablet tensile strength (TS) and disintegration time (DT) were measured before and after storage for 30 days at 40 degrees C and 75% relative humidity. An ensemble artificial neural network (EANN) was used to predict responses to differences in quantities of excipients and physical chemical properties of active ingredients in tablets. Most classical neural networks involve a tedious trial and error approach, but EANNs automatically determine basal key parameters, which ensure that an optimal structure is rapidly obtained. We compared the predictive abilities of EANNs in which the following kinds of training algorithms were used: linear, radial basis function, general regression (GR), and multilayer perceptron. The GR EANN predicted pharmaceutical responses such as TS and DT most accurately, as evidenced by high correlation coefficients in a leave-some-out cross-validation procedure. When used in conjunction with a tablet database, the GR EANN is capable of identifying acceptable candidate tablet formulations. PMID- 20310025 TI - An industry perspective on the monitoring of subvisible particles as a quality attribute for protein therapeutics. AB - Concern around the lack of monitoring of proteinaceous subvisible particulates in the 0.1-10 microm range has been heightened (Carpenter et al., 2009, J Pharm Sci 98: 1202-1205), primarily due to uncertainty around the potential immunogenicity risk from these particles. This article, representing the opinions of a number of industry scientists, aims to further the discussion by developing a common understanding around the technical capabilities, limitations, as well as utility of monitoring this size range; reiterating that the link between aggregation and clinical immunogenicity has not been unequivocally established; and emphasizing that such particles are present in marketed products which remain safe and efficacious despite the lack of monitoring. Measurement of subvisible particulates in the <10 microm size range has value as an aid in product development and characterization. Limitations in measurement technologies, variability from container/closure, concentration, viscosity, history, and inherent batch heterogeneity, make these measurements unsuitable as specification for release and stability or for comparability, at the present time. Such particles constitute microgram levels of protein with currently monitored sizes >or=10 microm representing the largest fraction. These levels are well below what is detected or reported for other product quality attributes. Subvisible particles remain a product quality attribute that is also qualified in clinical trials. PMID- 20310026 TI - A nonionic surfactant/chitosan micelle system in an innovative eye drop formulation. AB - Micelle systems composed of the polyoxyethylated nonionic surfactant Pluronic F127 (F127) and cationic polyelectrolyte chitosan (CH) were prepared with dexamethasone (DEX) as a hydrophobic model drug. The F127/CH micelles were characterised by their hydrodynamic diameter and a zeta-potential ranging between 25.4 and 28.9 nm and +9.3 and +17.6 mV, respectively. The DEX loading was between 0.48% and 0.56%, and no significant influence of CH on DEX loading was observed. All micelle systems were characterised by prolonged release profiles. The addition of CH significantly enhanced the in vitro DEX release rate and transport across Caco-2 cell monolayers, as compared to the CH-free F127 micelle system. This colloidal carrier was well tolerated in rabbit eyes, and no clinically abnormal signs in various ocular structures were observed. The increase in intraocular pressure (IOP) in rabbits was used to evaluate DEX ocular bioavailability. The AUC values showed a 1.7- and 2.4-fold increase in bioavailability with F127 and F127/0.015 (w/v) % CH micelle systems, respectively, as compared to a standard DEX suspension. These data indicate improved intraocular DEX absorption from the micelle systems, which can be ascribed to both F127 and CH corneal permeability enhancement. PMID- 20310027 TI - Camptocormia associated with an expanded allele in the TATA box-binding protein gene. PMID- 20310028 TI - Age of Parkinson's disease onset as a predictor for the development of dyskinesia. AB - The risk of developing levodopa-associated dyskinesia is known to vary inversely with the age of Parkinson's disease onset. This study quantifies dyskinesia risks for different Parkinson's onset ages in a patient population treated at the Parkinson's Disease Research, Education, and Clinical Center at the San Francisco Veterans Affairs Medical Center. Medical records were reviewed to determine age of Parkinson's onset, medication history, and dyskinesia onset. Dyskinesia risks were determined by using Kaplan-Meier analysis. Cox proportional hazard models were used to compare age groups and to perform multivariate modeling. This study included 109 patients with Parkinson's, 105 of whom had onset of symptoms after 1989. At 5 years of levodopa treatment, the dyskinesia risk for patients with onset age 40-49 was 70%, decreasing to 42% for onset ages 50-59, 33% for onset ages 60-69, and 24% for onset ages 70-79. Pairwise comparisons between the 40-49 age group and the other age groups were statistically significant in time-to event models. After 5 years of levodopa treatment, dyskinesia risks became uniformly high regardless of age of onset. These results suggest it is appropriate to use different baseline dyskinesia risks in clinical decision making for patients on the basis of their ages of onset. However, the most significant difference occurs between ages 40-49 and ages 50-79, and if more than 5 years of levodopa therapy are anticipated, dyskinesia risk may have less utility when deciding upon Parkinson's therapy. Drug studies for Parkinson's disease should also take age of Parkinson's onset into account when analyzing dyskinesia outcomes. PMID- 20310030 TI - Effect of histamine H2 receptor antagonism on levodopa-induced dyskinesia in the MPTP-macaque model of Parkinson's disease. AB - Levodopa-induced motor complications, including dyskinesia and wearing off, are troublesome side effects of treatment and impair quality of life in Parkinson's disease (PD) patients. The use of nondopaminergic agents as adjuncts to levodopa are potential options for managing these problems. Here, we asses the ability of the clinically available, selective histamine H(2) antagonist, famotidine (1, 3, and 30 mg/kg) to treat levodopa-induced dyskinesia and wearing off in the 1 methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-macaque model of PD. Famotidine (3 mg/kg) increased peak activity, enhanced peak anti-parkinsonian action (1 and 3 mg/kg), and extended duration of action (3 mg/kg, by 38%) of a low dose of levodopa (compared to low dose levodopa alone). Enhancement of anti-parkinsonian actions of low dose levodopa by famotidine (3 mg/kg) was associated with only mild, nondisabling dystonia. Famotidine had no effect on the anti-parkinsonian actions of high dose levodopa (compared to high dose levodopa alone). However, famotidine (1, 3, and 30 mg/kg) had a significant effect on chorea, but not dystonia, induced by high dose levodopa (compared to high dose levodopa alone). Famotidine increased high dose levodopa-induced "good quality" on time, i.e., on time not associated with disabling dyskinesia, by up to 28% (compared to high dose levodopa alone). In conclusion, famotidine, a drug currently available for use in the clinic, can enhance the peak-dose anti-parkinsonian actions and extend total duration of action of a low dose of levodopa, without producing disabling dyskinesia. Furthermore, in combination with a higher dose of levodopa, famotidine can reduce peak-dose levodopa-induced chorea and improve the quality of on-time. PMID- 20310029 TI - Neurochemical alterations in spinocerebellar ataxia type 1 and their correlations with clinical status. AB - Robust biomarkers of neurodegeneration are critical for testing of neuroprotective therapies. The clinical applicability of such biomarkers requires sufficient sensitivity to detect disease in individuals. Here we tested the sensitivity of high field (4 tesla) proton magnetic resonance spectroscopy ((1)H MRS) to neurochemical alterations in the cerebellum and brainstem in spinocerebellar ataxia type 1 (SCA1). We measured neurochemical profiles that consisted of 10 to 15 metabolite concentrations in the vermis, cerebellar hemispheres and pons of patients with SCA1 (N = 9) and healthy controls (N = 15). Total NAA (N-acetylaspartate + N-acetylaspartylglutamate, tNAA) and glutamate were lower and glutamine, myo-inositol and total creatine (creatine + phosphocreatine, tCr) were higher in patients relative to controls, consistent with neuronal dysfunction/loss, gliotic activity, and alterations in glutamate glutamine cycling and energy metabolism. Changes in tNAA, tCr, myo-inositol, and glutamate levels were discernible in individual spectra and the tNAA/myo-inositol ratio in the cerebellar hemispheres and pons differentiated the patients from controls with 100% specificity and sensitivity. In addition, tNAA, myo-inositol, and glutamate levels in the cerebellar hemispheres and the tNAA and myo-inositol levels in the pons correlated with ataxia scores (Scale for the Assessment and Rating of Ataxia, SARA). Two other biomarkers measured in the cerebrospinal fluid (CSF) of a subset of the volunteers (F(2)-isoprostanes asa marker of oxidative stress and glial fibrillary acidic protein (GFAP) as a marker of gliosis) were not different between patients and controls. These data demonstrate that (1)H MRS biomarkers can be utilized to noninvasively assess neuronal and glial status in individual ataxia patients. PMID- 20310031 TI - Higher serum uric acid associated with decreased Parkinson's disease prevalence in a large community-based survey. AB - A large community-based cross-sectional survey provided an opportunity to evaluate a previously reported association between Parkinson's disease (PD) and low serum uric acid (UA) levels in this population. The association between a self-reported PD diagnosis with treatment (n = 59) and serum UA level was examined using logistic and linear regression models, controlling for key covariates. In adjusted models, participants with UA levels at or above the median had a significantly lower odds of reporting PD with treatment compared with those with lower UA levels (OR 0.33, 95% CI 0.19-0.60, P = 0.0002). This association was observed for both men and women. The mean UA level among participants reporting PD with treatment was 0.78 mg/dl lower than the mean UA level among those not reporting PD (P or = 65 years with high-risk prostate cancer (T3 or T4N0M0, prostate specific antigen >20 ng/mL, and/or Gleason score 8-10) who received either brachytherapy alone (n = 206) or CMT (n = 558) at the Chicago Prostate Cancer Center or at a 21st Century Oncology facility. Men either had no history of myocardial infarction (MI) or had a history of MI treated with a stent or surgical intervention. Fine and Gray regression analysis was used to identify the factors associated with PCSM. RESULTS: The median patient age was 73 years (interquartile range, 70-77 years). After a median follow-up of 4.9 years, 25 men died of prostate cancer. After adjusting for age and prostate cancer prognostic factors, the risk of PCSM was significantly less (adjusted hazard ratio, 0.29; 95% confidence interval, 0.12-0.68; P = .004) for men who received CMT than for men who received brachytherapy alone. Other factors that were associated significantly with an increased risk of PCSM included a Gleason score of 8 to 10 (P = .017). CONCLUSIONS: Elderly men who had high-risk prostate cancer without cardiovascular disease or with surgically corrected cardiovascular disease had a lower risk of PCSM when they received CMT than when they received brachytherapy alone. These results support aggressive locoregional treatment in healthy elderly men with high-risk prostate cancer. PMID- 20310057 TI - Analysis of sesterterpenoids from Aspergillus terreus using ESI-QTOF and ESI-IT. AB - INTRODUCTION: Biosynthesis of terretonin was studied due to the interesting skeleton of this series of sesterterpenoids. Very recently, Lopez-Gresa reported two new sesterterpenoids (terretonins E and F) which are inhibitors of the mammalian mitochondrial respiratory chain. Mass spectrometry (MS), especially tandem mass spectrometry, has been one of the most important physicochemical methods for the identification of trace natural products due to it rapidity, sensitivity and low levels of sample consumption. The potential application prospect and unique skeleton prompted us to study structural characterisation using MS. OBJECTIVE: To obtain sufficient information for rapid structural elucidation of this class of compounds using MS. METHODOLOGY: The elemental composition of the product ions was confirmed by low-energy ESI-CID-QTOF-MS/MS analyses. The fragmentation pathways were postulated on the basis of ESI-QTOF MS/MS/MS and ESI-IT-MS(n) spectra. Common features and major differences between ESI-QTOF-MS/MS and IT-MS(n) spectra were compared. For ESI-QTOF-MS/MS/MS experiments, capillary exit voltage was raised to induce in-source dissociation. Ammonium acetate or acetic acid were added into solutions to improve the intensity of [M + H]+. The collision energy was optimised to achieve sufficient fragmentation. Some fragmentation pathways were unambiguously proposed by the variety of abundance of fragment ions at different collision energies even without MS(n) spectra. RESULTS: Fragmentation pathways of five representative sesterterpenoids were elucidated using ESI-QTOF-MS/MS/MS and ESI-IT-MS(n) in both positive- and negative-ion mode. The key group of characterising fragmentation profiles was ring B, and these fragmentation patterns are helpful to identify different types of sestertepenoids. CONCLUSION: Complementary information obtained from fragmentation experiments of [M + H]+ (or [M + NH4]+ and [M-H](-) precursor ions is especially valuable for rapid identification of this kind of sesterterpenoid. PMID- 20310056 TI - Cervical cancer prevention: new tools and old barriers. AB - Cervical cancer is the second most common female tumor worldwide, and its incidence is disproportionately high (>80%) in the developing world. In the United States, in which Papanicolaou (Pap) tests have reduced the annual incidence to approximately 11,000 cervical cancers, >60% of cases are reported to occur in medically underserved populations as part of a complex of diseases linked to poverty, race/ethnicity, and/or health disparities. Because carcinogenic human papillomavirus (HPV) infections cause virtually all cervical cancer, 2 new approaches for cervical cancer prevention have emerged: 1) HPV vaccination to prevent infections in younger women (aged < or =18 years) and 2) carcinogenic HPV detection in older women (aged > or =30 years). Together, HPV vaccination and testing, if used in an age-appropriate manner, have the potential to transform cervical cancer prevention, particularly among underserved populations. Nevertheless, significant barriers of access, acceptability, and adoption to any cervical cancer prevention strategy remain. Without understanding and addressing these obstacles, these promising new tools for cervical cancer prevention may be futile. In the current study, the delivery of cervical cancer prevention strategies to these US populations that experience a high cervical cancer burden (African-American women in South Carolina, Alabama, and Mississippi; Haitian immigrant women in Miami; Hispanic women in the US-Mexico Border; Sioux/Native American women in the Northern Plains; white women in the Appalachia; and Vietnamese-American women in Pennsylvania and New Jersey) is reviewed. The goal was to inform future research and outreach efforts to reduce the burden of cervical cancer in underserved populations. PMID- 20310058 TI - A new species of Pseudoloris (Omomyidae, Primates) from the middle Eocene of Sant Jaume de Frontanya (Eastern Pyrenees, Spain). AB - In this article we describe a new species of Pseudoloris (Omomyidae, Primates) from the Robiacian (middle Eocene) locality of Sant Jaume de Frontanya (Eastern Pyrenees, Spain). Pseudoloris pyrenaicus is characterized by its medium size, thickened paracristid, absence of a distinct paraconid, and well-developed buccal cingulid in the lower molars, large hypoconulid in the M(3), paraconule and hypocone reduced in the M(1) and M(2) and absent in the M(3). The material from Sant Jaume de Frontanya constitutes the most abundant sample of the genus Pseudoloris found until now in the Iberian Peninsula. Almost all the dental elements have been recovered, including those teeth hardly known for other species of the genus, such as lower and upper incisors. The new species shows intermediate features between Pseudoloris isabenae from Capella and Pseudoloris parvulus, present in different Spanish and French sites. Therefore, we consider that Pseudoloris pyrenaicus is an intermediate form between these two species. PMID- 20310059 TI - Waddling and toddling: the biomechanical effects of an immature gait. AB - Femoral shape changes during the course of human growth, transitioning from a subcircular tube to a teardrop-shaped diaphysis with a posterior pilaster. Differences between immature and mature bipedalism and body shape may generate different loads, which, in turn, may influence femoral modeling and remodeling during the course of the human lifespan. This study uses two different approaches to evaluate the hypotheses that differences in gait between young and mature walkers result in differences in ground reaction forces (GRFs) and that the differences in loading regimes between young children and adults will be reflected in the geometric structure of the midshaft femur. The results of this analysis indicate that GRFs differ between young walkers and adults in that normalized mediolateral (ML) forces are significantly higher in younger age groups. In addition, these differences between children and adults in the relative level of ML bending force are reflected in changes in femoral geometry during growth. During the earlier stages of human development, immature femoral diaphyses are heavily reinforced in approximately ML plane. The differences in gait between mature and immature walkers, and hence the differences in femoral shape, are likely partially a product of a minimal bicondylar angle and relatively broad body in young children. PMID- 20310060 TI - Tolerant food sharing and reciprocity is precluded by despotism among bonobos but not chimpanzees. AB - Tolerant food sharing among human foragers can largely be explained by reciprocity. In contrast, food sharing among chimpanzees and bonobos may not always reflect reciprocity, which could be explained by different dominance styles: in egalitarian societies reciprocity is expressed freely, while in more despotic groups dominants may hinder reciprocity. We tested the degree of reciprocity and the influence of dominance on food sharing among chimpanzees and bonobos in two captive groups. First, we found that chimpanzees shared more frequently, more tolerantly, and more actively than bonobos. Second, among chimpanzees, food received was the best predictor of food shared, indicating reciprocal exchange, whereas among bonobos transfers were mostly unidirectional. Third, chimpanzees had a shallower and less linear dominance hierarchy, indicating that they were less despotic than bonobos. This suggests that the tolerant and reciprocal sharing found in chimpanzees, but not bonobos, was made possible by the absence of despotism. To investigate this further, we tested the relationship between despotism and reciprocity in grooming using data from an additional five groups and five different study periods on the main groups. The results showed that i) all chimpanzee groups were less despotic and groomed more reciprocally than bonobo groups, and ii) there was a general negative correlation between despotism and grooming reciprocity across species. This indicates that an egalitarian hierarchy may be more common in chimpanzees, at least in captivity, thus fostering reciprocal exchange. We conclude that a shallow dominance hierarchy was a necessary precondition for the evolution of human-like reciprocal food sharing. PMID- 20310062 TI - Prezygapophyseal articular facet shape in the catarrhine thoracolumbar vertebral column. AB - Two contrasting patterns of lumbar vertebral morphology generally characterize anthropoids. "Long-backed" monkeys are distinguished from "short-backed" apes [Benton: The baboon in medical research, Vol. 2 (1967:201)] with respect to several vertebral features thought to afford greater spinal flexibility in the former and spinal rigidity in the latter. Yet, discussions of spinal mobility are lacking important functional insight that can be gained by analysis of the zygapophyses, the spine's synovial joints responsible for allowing and resisting intervertebral movements. Here, prezygapophyseal articular facet (PAF) shape in the thoracolumbar spine of Papio, Hylobates, Pongo, Gorilla, and Pan is evaluated in the context of the "long-backed" versus "short-backed" model. A three dimensional geometric morphometric approach is used to examine how PAF shape changes along the thoracolumbar vertebral column of each taxon and how PAF shape varies across taxa at corresponding vertebral levels. The thoracolumbar transition in PAF shape differs between Papio and the hominoids, between Hylobates and the great apes, and to a lesser extent, among great apes. At the level of the first lumbar vertebra, the PAF shape of Papio is distinguished from that of hominoids. At the level of the second lumbar vertebra, there is variation to some extent among all taxa. These findings suggest that morphological and functional distinctions in primate vertebral anatomy may be more complex than suggested by a "long-backed" versus "short-backed" dichotomy. PMID- 20310061 TI - Functional significance of genetic variation underlying limb bone diaphyseal structure. AB - Limb bone diaphyseal structure is frequently used to infer hominin activity levels from skeletal remains, an approach based on the well-documented ability of bone to adjust to its loading environment during life. However, diaphyseal structure is also determined in part by genetic factors. This study investigates the possibility that genetic variation underlying diaphyseal structure is influenced by the activity levels of ancestral populations and might also have functional significance in an evolutionary context. We adopted an experimental evolution approach and tested for differences in femoral diaphyseal structure in 1-week-old mice from a line that had been artificially selected (45 generations) for high voluntary wheel running and non-selected controls. As adults, selected mice are significantly more active on wheels and in home cages, and have thicker diaphyses. Structural differences at 1 week can be assumed to primarily reflect the effects of selective breeding rather than direct mechanical stimuli, given that the onset of locomotion in mice is shortly after Day 7. We hypothesized that if genetically determined diaphyseal structure reflects the activity patterns of members of a lineage, then selected animals will have relatively larger diaphyseal dimensions at 1 week compared to controls. The results provide strong support for this hypothesis and suggest that limb bone cross sections may not always only reflect the activity levels of particular fossil individuals, but also convey an evolutionary signal providing information about hominin activity in the past. PMID- 20310063 TI - Testosterone, physical activity, and somatic outcomes among Filipino males. AB - Testosterone (T) facilitates male investment in reproduction in part through its anabolic effects on skeletal muscle. Traits like muscle and strength are energetically costly but are believed to enhance competitive ability in humans and other mammals. However, there are limited data on relationships between T and somatic outcomes in lean, non-western populations. We evaluate relationships between waking and pre-bed salivary T and adiposity, fat-free mass (FFM), arm muscle area (AMA), and grip strength (GS) in a large, population-based birth cohort of young adult Filipino males (20.8-22.6 years, n = 872). Data were collected as part of the Cebu Longitudinal Health and Nutrition Survey. Neither waking nor evening T predicted FFM, AMA, or GS. However, there were borderline or significant interactions between T and basketball playing (the most common team sport) and weight lifting as predictors of outcomes: higher waking T predicted higher FFM (activity x T interaction P < 0.01), AMA (interaction P < 0.1), and GS (interaction P < 0.02) among frequent basketball players, and GS (interaction P < 0.09) among the smaller sample of weight lifters. In contrast to clinical studies, but consistent with findings in several subsistence-level populations, T was positively related to adiposity in these lean young males, suggesting that energy status might regulate circulating T. Our findings support a role of the prewaking rise in T as a determinant of energetic allocation to lean mass and strength in the context of repeated muscular use and support the hypothesized role of T as a mediator of investment in costly somatic traits in human males. PMID- 20310064 TI - Brief communication: The London atlas of human tooth development and eruption. AB - The aim of this study was to develop a comprehensive evidence-based atlas to estimate age using both tooth development and alveolar eruption for human individuals between 28 weeks in utero and 23 years. This was a cross-sectional, retrospective study of archived material with the sample aged 2 years and older having a uniform age and sex distribution. Developing teeth from 72 prenatal and 104 postnatal skeletal remains of known age-at-death were examined from collections held at the Royal College of Surgeons of England and the Natural History Museum, London, UK (M 91, F 72, unknown sex 13). Data were also collected from dental radiographs of living individuals (M 264, F 264). Median stage for tooth development and eruption for all age categories was used to construct the atlas. Tooth development was determined according to Moorrees et al. (J Dent Res 42 (1963a) 490-502; Am J Phys Anthropol 21 (1963b) 205-213) and eruption was assessed relative to the alveolar bone level. Intraexaminer reproducibility calculated using Kappa on 150 teeth was 0.90 for 15 skeletal remains of age <2 years, and 0.81 from 605 teeth (50 radiographs). Age categories were monthly in the last trimester, 2 weeks perinatally, 3-month intervals during the first year, and at every year thereafter. Results show that tooth formation is least variable in infancy and most variable after the age of 16 years for the development of the third molar. PMID- 20310065 TI - Steric and thermodynamic limits of design for the incorporation of large unnatural amino acids in aminoacyl-tRNA synthetase enzymes. AB - Orthogonal aminoacyl-tRNA synthetase/tRNA pairs from archaea have been evolved to facilitate site specific in vivo incorporation of unnatural amino acids into proteins in Escherichia coli. Using this approach, unnatural amino acids have been successfully incorporated with high translational efficiency and fidelity. In this study, CHARMM-based molecular docking and free energy calculations were used to evaluate rational design of specific protein-ligand interactions for aminoacyl-tRNA synthetases. A series of novel unnatural amino acid ligands were docked into the p-benzoyl-L-phenylalanine tRNA synthetase, which revealed that the binding pocket of the enzyme does not provide sufficient space for significantly larger ligands. Specific binding site residues were mutated to alanine to create additional space to accommodate larger target ligands, and then mutations were introduced to improve binding free energy. This approach was used to redesign binding sites for several different target ligands, which were then tested against the standard 20 amino acids to verify target specificity. Only the synthetase designed to bind Man-alpha-O-Tyr was predicted to be sufficiently selective for the target ligand and also thermodynamically stable. Our study suggests that extensive redesign of the tRNA synthatase binding pocket for large bulky ligands may be quite thermodynamically unfavorable. PMID- 20310067 TI - Solution structure of the N-terminal domain of Bacillus subtilis delta subunit of RNA polymerase and its classification based on structural homologs. PMID- 20310066 TI - Structures of the autoproteolytic domain from the Saccharomyces cerevisiae nuclear pore complex component, Nup145. PMID- 20310068 TI - Crystal structures of holo and Cu-deficient Cu/Zn-SOD from the silkworm Bombyx mori and the implications in amyotrophic lateral sclerosis. PMID- 20310069 TI - An ancient anion-binding structural module in RNA and DNA helicases. AB - RNA and DNA helicases manipulate or translocate along single strands of nucleic acids by grasping them using a conserved structural motif. We have examined the available crystal structures of helicases of the two principal superfamilies, SF1 and SF2, and observed that the most conserved interactions with the nucleic acid occur between the phosphosugar backbone of a trinucleotide and the three strand helix loops within a (beta-strand/alpha-helix)(3) structural module. At the first and third loops is a conserved hydrogen-bonded feature called a thr-motif, often seen at alpha-helical N-termini, with the threonine as the N-cap residue. These loops can be aligned with few insertions or deletions, and their main chain atoms are structurally congruent amongst the family members and between the two modules found as tandem pairs in all SF1 and SF2 proteins. The other highly conserved interactions with nucleic acid involve main chain NH groups, often at the helical N-termini, interacting with phosphate groups. We comment on how the sequence motifs that are commonly used to identify helicases map to locations on the module and discuss the implications of the conserved orientation of nucleic acid on the surface of the module for directional stepping along DNA or RNA. PMID- 20310070 TI - Physiotherapists' participation in peer review in New Zealand: implications for the profession. AB - BACKGROUND AND PURPOSE: Peer review is increasingly used for professional development and to monitor physiotherapists' competence to practice. This study set out to describe the experience of participating in peer review. METHOD: Qualitative descriptive methods were employed to elicit and analyze interview data from physiotherapists with experience as reviewers and having their practice reviewed. RESULTS: Reviewers managed the process to provide an appropriate level of challenge to junior and senior therapists, and to avoid disrupting professional relationships. Those being reviewed reduced anxiety about the process and risk of negative feedback by putting their best practice on show, and where they could, by carefully choosing the reviewer and patient interaction to be reviewed. CONCLUSION: When peer review has competing purposes it is neither an effective professional development tool nor an accurate measure of competence. Power and interpersonal relationships need to be acknowledged if peer review is used to assess practitioner competence. PMID- 20310071 TI - Physiotherapy-provided operant conditioning in the management of low back pain disability: A systematic review. AB - BACKGROUND AND PURPOSE: Non-specific low back pain (LBP) is a leading cause of disability in developed countries. Behavioural interventions have been found efficacious in reducing disability in LBP. Operant conditioning is one type of behavioural intervention being employed by physiotherapists; however, the effectiveness of physiotherapist-provided operant conditioning (POC) in the management of LBP disability is unknown. This review aims to answer the question: is POC more effective than comparison interventions in reducing LBP disability? METHOD: A systematic review of randomized controlled trials was conducted using a qualitative analysis of effect. Participants were adults >=18 years with non specific LBP. The intervention was defined as a time contingent, graduated increase in activity including goal setting and the education and reinforcement of positive pain behaviours with the aim of decreasing disability. The primary outcome measure was back pain specific disability. Secondary outcomes included generic functional status, pain intensity, sick leave, fear avoidance beliefs or behaviour and adverse effects. RESULTS: Fifteen trials involving 3737 people were included. Eight studies reported a clinically significant difference. The POC intervention was not found to be inferior to any of the comparison interventions in reducing disability. Moderate evidence was found that POC is more effective than other behavioural interventions in reducing long term disability in chronic LBP. Moderate evidence showed POC may be more effective than other treatments in reducing post-treatment fear avoidance beliefs in a sub acute population but less effective in reducing short term fear avoidance beliefs in a population with mixed LBP. Moderate evidence showed POC is more effective than a placebo intervention in reducing short term pain in sub-acute LBP. CONCLUSION: POC may be considered efficacious in the treatment of LBP. Physiotherapists may also consider POC for its additional effect of reducing long term disability in chronic LBP. PMID- 20310072 TI - A validated liquid chromatography-electrospray ionization-mass spectrometry method for quantification of spilanthol in Spilanthes acmella (L.) Murr. AB - INTRODUCTION: The medicinal plant Spilanthes acmella (L.) Murr. has demonstrated an array of biological activities that are generally attributed to the presence of spilanthol and other alkylamides. Recently this plant has been of interest due to its potential for the treatment and prevention of malaria. OBJECTIVE: The aim of this study was to develop a liquid chromatography-electrospray ionisation-mass spectrometry (HPLC-esiMS) method for rapid identification and quantification of the alkylamide spilanthol from S. acmella. METHODOLOGY: Hydroethanolic extracts were prepared from fresh S. acmella using different percentages of ethanol and were stored at -80, -20 and 25 degrees C. Spilanthol was isolated and used as a standard for quantitative analysis. RESULTS: Validation parameters for the HPLC esiMS analysis of spilanthol were as follows: repeatability, <= 6%; intermediate precision, <= 2%; range, 0.45-450 um; limit of detection, 0.27 um; and limit of quantification, 0.45 um. Eight alkylamides in the S. acmella extract were identified based on MS-MS fragmentation patterns, and NMR analysis confirmed the identity of the most abundant of these as spilanthol. Spilanthol was extracted most efficiently in solvents containing >75% ethanol, and was stable in ethanolic extracts stored at all three temperatures. CONCLUSION: These results demonstrate the effectiveness of HPLC-esiMS for quantitative and qualitative analysis of spilanthol. We show that spilanthol is effectively extracted in ethanol, and is stable in ethanol extracts for over 6 months, even at room temperature. PMID- 20310073 TI - Comparative quantitative analysis of artemisinin by chromatography and qNMR. AB - INTRODUCTION: Since the discovery of artemisinin in the 1970s, many techniques based on diverse chromatography techniques have been developed to detect and quantify this important antiplasmodial compound. The accurate quantification of this compound in the Artemisia annua plant material is mainly needed for breeding purposes in order to cultivate higher yielding varieties. It is also important for the quality control of herbal preparations containing A. annua plant material. OBJECTIVE: To evaluate the most common validated quantification techniques (LC-MS, HPLC-ELSD and TLC) and compare the results to quantitative nuclear magnetic resonance spectroscopy (qNMR) in eight different A. annua samples collected from around the world. METHODOLOGY: The leaf material were extracted according to standard procedures and analysed with the validated quantification techniques. For the qNMR analysis we did not employ a standard curve but instead used an internal standard (maleid acid) which is not chemically related to artemisinin. RESULTS: We found a significant difference between the results in this study. Compared with the qNMR results the HPLC-ELSD corresponded closely, followed by LC-MS. Quantitation with TLC led to an estimation range of 0.5 to +3.2 mg artemisinin/g of A. annua. CONCLUSION: These results imply that qNMR, with the addition of an internal standard, can be used to quantify artemisinin in A. annua samples in a rapid and reproducible manner. PMID- 20310074 TI - Rapid method for simultaneous determination of 20 components in Isodon nervosa by high-performance liquid chromatography-electrospray ionisation tandem mass spectrometry. AB - INTRODUCTION: Isodon nervosa is a commonly used traditional Chinese medicine including diterpenoids, phenolic acids, triterpenoids and volatile oil. Qualitative and quantitative analysis of multi-components is important for its quality control. OBJECTIVE: To establish a liquid chromatography-electrospray ionisation-mass spectrometry method for simultaneous analysis of 20 bioactive constituents of Isodon nervosa in different places of China and different parts of this herb. METHODOLOGY: The optimal chromatographic conditions were achieved on a C(18) column (250 * 4.6 mm, 5 um) with with linear gradient elution with 0.1% aqueous formic acid : methanol containing 0.1% formic acid at a flow-rate of 0.7 mL/min in 15 min. The identification and quantification of those analytes were achieved on a hybrid quadrupole linear ion trap mass spectrometer. Multiple reaction monitoring scanning was employed for quantification with switching electrospray ion source polarity between positive and negative modes in a single run. Full validation of the method was carried out (linearity, precision, accuracy, limit of detection and limit of quantification). RESULTS: The results indicated that the method was simple, rapid, specific and reliable. The proposed method was successfully applied for the qualitative and quantitative analysis of 20 chemical compositions in Isodon nervosa samples. CONCLUSION: Twenty chemical compositions in 21 batches of wild and cultivated Isodon nervosa samples from different sources had great variation in the contents. PMID- 20310075 TI - Development and validation of a micellar electrokinetic chromatography method for quantitative determination of butenolides in Piper malacophyllum (C. Presl) C. DC. AB - INTRODUCTION: A large number of natural and synthetic compounds having butenolides as a core unit have been described and many of them display a wide range of biological activities. Butenolides from P. malacophyllum have presented potential antifungal activities but no specific, fast, and precise method has been developed for their determination. OBJECTIVE: To develop a methodology based on micellar electrokinetic chromatography to determine butenolides in Piper species. METHODOLOGY: The extracts were analysed in an uncoated fused-silica capillaries and for the micellar system 20 mmol/L SDS, 20% (v/v) acetonitrile (ACN) and 10 mmol/L STB aqueous buffer at pH 9.2 were used. The method was validated for precision, linearity, limit of detection (LOD) and limit of quantitation (LOQ) and the standard deviations were determined from the standard errors estimated by the regression line. RESULTS: A micellar electrokinetic chromatography (MEKC) method for determination of butenolides in extracts gave full resolution for 1 and 2. The analytical curve in the range 10.0-50.0 ug/mL (r(2) = 0.999) provided LOD and LOQ for 1 and 2 of 2.1/6.3 and 1.1/3.5 ug/mL, respectively. The RSD for migration times were 0.12 and 1.0% for peak area ratios with 100.0 +/- 1.4% of recovery. CONCLUSIONS: A novel high-performance MEKC method developed for the analysis of butenolides 1 and 2 in leaf extracts of P. malacophyllum allowed their quantitative determined within an analysis time shorter than 5 min and the results indicated CE to be a feasible analytical technique for the quantitative determination of butenolides in Piper extracts. PMID- 20310076 TI - Preparative separation of chlorogenic acid by centrifugal partition chromatography from highbush blueberry leaves (Vaccinium corymbosum L.). AB - INTRODUCTION: Blueberries (genus Vaccinium) have gained worldwide focus because of the high anthocyanin content of their fruits. In contrast, the leaves of blueberry have not attracted any attention, even though they contain large quantities of chlorogenic acid, a strong antioxidant compound. OBJECTIVE: The aim of this investigation was the quantification and preparative isolation of chlorogenic acid (5-caffeoylquinic acid, 5-CQA) from blueberry leaves using a new separation scheme, centrifugal partition chromatography (CPC). METHODOLOGY: A water fraction containing a high concentration of 5-CQA (14.5% of dry weight extract) was obtained by defatting a crude methanol extract from blueberry leaves. CPC was applied to isolate 5-CQA from this water fraction using a two phase solvent system of ethyl acetate-ethanol-water at a volume ratio 4:1:5 (v/v/v). The flow-rate of mobile phase was 2 mL/min with the ascending mode while rotating at 1200 rpm. The eluate was monitored at 330 nm. The structure of chlorogenic acid in the CPC fraction was confirmed with HPLC, UV, ESI/MS and NMR spectra. RESULTS: The HPLC chromatogram showed that the fractions collected by CPC contained chlorogenic acid with 96% purity based on peak area percentage. The total amount of chlorogenic acid isolated from 0.5 g of a water fraction was 52.9 mg, corresponding to 10.6% of the water fraction. The isolated compound was identified successively as 5-CQA with MS (parent ion at m/z 355.1 [M + H](+)) and (1)H NMR spectra [caffeoyl moiety in the down field (delta 6.0-8.0 ppm) and quinic acid moiety in the up field (delta 2.0-5.5 ppm)]. CONCLUSION: 5-CQA was successfully isolated from blueberry leaves by the CPC method in a one-step procedure, indicating a further potential use for blueberry leaves. PMID- 20310077 TI - A nitromethane-based HPLC system alternative to acetonitrile for carotenoid analysis of fruit and vegetables. AB - Acetonitrile-based HPLC systems are the most commonly used for carotenoid analysis from different plant tissues. Because of the acetonitrile shortage, an HPLC system for the separation of carotenoids on C(18) reversed-phase columns was developed in which an acetonitrile-alcohol-based mobile phase was replaced by nitromethane. This solvent comes closest to acetonitrile with respect to its elutrophic property. Our criterion was to obtain similar separation and retention times for a range of differently structured carotenoids. This was achieved by further increase in the lipophilicity with ethylacetate. For all the carotenoids which we tested, we found co-elution only of beta-cryptoxanthin and lycopene. By addition of 1% of water, separation of this pair of carotenoids was also achieved. The final recommended mobile phase consisted of nitromethane : 2 propanol : ethyl acetate : water (79 : 10 : 10 : 1, by volume). On Nucleosil C(18) columns and related ones like Hypersil C(18), we obtained separation of carotenes, hydroxyl, epoxy and keto derivatives, which resembles the excellent separation properties of acetonitrile-based mobile phases on C(18) reversed phase columns. We successfully applied the newly developed HPLC system to the separation of carotenoids from different vegetables and fruit. PMID- 20310078 TI - Sex dimorphism in gray/white matter volume and diffusion tensor during normal aging. AB - The purpose of this study is to elucidate sex differences in global and regional gray/white matter volume, mean diffusivity (MD), and fractional anisotropy (FA) during normal aging using voxel-based analysis. We studied 245 healthy right handed subjects with a wide range of ages (115 women, 22-70 years; 130 men, 21-71 years). Regarding global effects, inclusion of a quadratic age term improved the fit to data for white matter fraction and MD, but not for global gray matter volume/fraction or FA. Regarding regional effects, we found anterior-dominant volume loss, FA decrease predominantly in the anterior white matter, and MD increase predominantly in perisylvian regions and periventricular white matter against age for both sexes. Compared with women, we found a steeper FA decline for men in the right inferior fronto-temporal areas, extending to the anterior cingulate cortex, and an accelerated MD increase for men in the bilateral frontal, temporal, and parietal areas. There was no area in which interaction of sex with age was significant for regional volume, or in which a steeper FA decline or accelerated MD increase for women was significant. Our results provide strong evidence of sex dimorphism in global and focal diffusion characteristics during normal aging. PMID- 20310079 TI - Proceedings from the XIth International Symposium on Advances in Targeted Therapies, 22 to 26 April 2009. PMID- 20310080 TI - Proceedings from the symposium Cell Therapy, Bioengineering and Regenerative Medicine, September 2008, Nancy, France. PMID- 20310081 TI - CQ sources/bibliography. PMID- 20310082 TI - Reliability of heart rate variability measurements in patients with a history of myocardial infarction. AB - Despite a well-established prognostic value in cardiac patients, HRV (heart rate variability) indexes have been used little in the clinical setting. Poor reliability of the measurements might be a possible explanation for this. In the present study, we assessed the reliability of short-term HRV indexes in post-MI (myocardial infarction) patients. We studied 61 MI patients [50 males; age, 59+/ 8 years; and LVEF (left ventricular ejection fraction), 46+/-6%; values are means +/-S.D.],who underwent a 5+5 min ECG recording during spontaneous and paced breathing on two consecutive days. Standard time-domain [SDNN (S.D. of RR interval values) and RMSSD (root- mean-square of successive RR interval differences)] and frequency-domain [LF (low-frequency) and HF (high-frequency) power, and LF/HF] indexes of HRV were computed. Absolute and relative reliability were assessed by the 95% limits of random variation and by the ICC (intra-class correlation coefficient). The agreement between the two measurements in classifying patients at low or high risk, according to different cut-points, and the sample size needed to detect a clinically relevant change, were also assessed. During spontaneous breathing, individual changes in test-retest measurements ranged from -41 to + 61% (SDNN; best case) and from -76 to + 316% (LF/HF; worst case). The ICC ranged from 0.72 to 0.81. Most patients (79-90 %) were assigned to the same class by the two measurements. Paced breathing did not improve reliability. In conclusion, short-term HRV parameters in MI patients may have large day-to-day variations, making the detection of treatment effects in individual patients difficult; however, the ICC values and the analysis of the consistency of classification between repeated tests indicate that HRV measurements fulfill the criteria required to be used for diagnostic or classification purposes. PMID- 20310083 TI - Prevention of myocardial fibrosis by N-acetyl-seryl-aspartyl-lysyl-proline in diabetic rats. AB - Ac-SDKP (N-acetyl-seryl-aspartyl-lysyl-proline) is a physiological tetrapeptide hydrolysed by ACE (angiotensin-converting enzyme). In experimental models of hypertension, Ac-SDKP has antifibrotic effects in the heart; however, the role of Ac-SDKP in diabetic cardiomyopathy is currently unknown. The aim of the present study was to evaluate the effect of Ac-SDKP on cardiac systolic and diastolic function, and interstitial and perivascular fibrosis in the heart of diabetic rats.Diabetes was induced in 55 Sprague-Dawley rats by streptozotocin injection. Control rats (n=18)underwent only buffer injection.Out of the 55 diabetic rats, 19 were chronically treated with insulin and 13 with the ACEI (ACE inhibitor) ramipril (3 mg x kg(-1 )of body weight x day(-1)). At 2 months after the onset of diabetes, Ac-SDKP (1 mg x kg(-1) of body weight x day(-1)) was administered by osmotic minipumps for 8 weeks to eight control rats, 13 diabetic rats, seven diabetic rats treated with ramipril and nine insulin-treated diabetic rats. Diabetic rats had a significant increase in blood glucose levels. Left ventricular interstitial and perivascular fibrosis, and TGF-beta1 (transforming growth factor-beta1) protein levels were increased in diabetic rats, but not in insulin-treated diabetic rats and ramipril-treated diabetic rats, compared with control rats. Ac-SDKP administration significantly reduced left ventricular interstitial and perivascular fibrosis in diabetic rats and in diabetic rats treated with ramipril. This was accompanied by a significant reduction in active TGF-beta1 and phospho-Smad2/3 protein levels in myocardial tissue of diabetic rats. Echocardiography showed that diabetes was associated with increased end systolic diameters, and depressed global systolic function and diastolic dysfunction, as assessed by transmitral Doppler velocity profile. These changes were completely reversed by insulin or ramipril treatment. Ac-SDKP treatment partially restored diastolic function in diabetic rats. In conclusion, Ac-SDKP administration in diabetic rats reduces left ventricular interstitial and perivascular fibrosis, active TGF-beta1 and phospho-Smad2/3levels, and improves diastolic function. Taken together, these findings suggest that, by inhibiting theTGF-beta/Smad pathway, Ac-SDKP protects against the development of diabetic cardiomyopathy PMID- 20310084 TI - Skeletal muscle metabolic recovery following submaximal exercise in chronic heart failure is limited more by O(2) delivery than O(2) utilization. AB - CHF (chronic heart failure) is associated with a prolonged recovery of skeletal muscle energy stores following submaximal exercise, limiting the ability to perform repetitive daily activities.However, the pathophysiological background of this impairment is not well established. The aim of the present study was to investigate whether muscle metabolic recovery following submaximal exercise in patients with CHF is limited by O2 delivery or O2 utilization. A total of 13 stable CHF patients (New York Heart Association classes II-III) and eight healthy subjects, matched for age and BMI (body mass index), were included. All subjects performed repetitive submaximal dynamic single leg extensions in the supine position. Post-exercise PCr (phosphocreatine) resynthesis was assessed by 31P-MRS (magnetic resonance spectroscopy). NIRS (near-IR spectroscopy) was applied simultaneously, using the rate of decrease in HHb (deoxygenated haemoglobin) as an index of post-exercise muscle re-oxygenation. As expected, PCr recovery was slower in CHF patients than in control subjects (time constant, 47+/-10 compared with 35+/-12 s respectively; P=0.04). HHb recovery kinetics were also prolonged in CHF patients (mean response time, 74+/-41 compared with 44+/-17 s respectively; P=0.04). In the patient group, HHb recovery kinetics were slower than PCr recovery kinetics (P=0.02), whereas no difference existed in the control group(P=0.32). In conclusion, prolonged metabolic recovery in CHF patients is associated with an even slower muscle tissue re-oxygenation, indicating a lower O(2) delivery relative to metabolic demands. Therefore we postulate that the impaired ability to perform repetitive daily activities in these patients depends more on a reduced muscle blood flow than on limitations in O(2) utilization. PMID- 20310085 TI - Regulation of resistin by cyclic mechanical stretch in cultured rat vascular smooth muscle cells. AB - Resistin has a potential role in atherosclerosis; however, the molecular mechanism underlying the increase in resistin expression in atherosclerosis remains unclear. As mechanical stretch plays an important role in atherosclerosis, in the present study we sought to investigate the cellular and molecular mechanisms underlying the regulation of resistin by cyclic mechanical stretch in VSMCs (vascular smooth muscle cells). VSMCs from thoracic aorta of adult Wistar rats were cultured and subjected to cyclic stretch. Cyclic mechanical stretch significantly increased resistin protein and mRNA expression as compared with control cells without stretch. The specific p38 MAPK (mitogen activated protein kinase) inhibitor SB203580, the antioxidant N-acetylcysteine and p38 MAPK siRNA (small interfering RNA) attenuated the induction of resistin protein by cyclic stretch. Cyclic stretch significantly increased the phosphorylation of p38 MAPK, whereas pre-treatment with SB203580 and N acetylcysteine significantly inhibited this effect. Cyclic stretch significantly increased ROS (reactive oxygen species) production, and pre-treatment with N acetylcysteine significantly inhibited stretch-induced ROS production. Cyclic stretch also increased STAT3 (signal transducer and activator of transcription 3) binding activity and resistin promoter activity, and resistin promoter activity was abolished when STAT3 in the promoter area was mutated. Pre-treatment with SB203580 and N-acetylcysteine significantly attenuated resistin promoter activity induced by cyclic stretch. Cyclic stretch increased the secretion of AngII (angiotensin II) and resistin from cultured VSMCs. Exogenous AngII increased resistin expression, and AngII receptor inhibition attenuated this effect. In conclusion, cyclic mechanical stretch increases resistin expression in cultured rat VSMCs. Stretch-induced resistin expression is mediated through ROS, and the p38 MAPK and STAT3 pathways. Therefore resistin induced by cyclic stretch may contribute to the pathogenesis of atherosclerosis under haemodynamic overload.Key PMID- 20310086 TI - [Deep brain stimulation in mood disorders: is it as easy as it seems?]. PMID- 20310088 TI - On Renal Activity: A new View of the Function of the Glomerulus. PMID- 20310087 TI - [Infant and early childhood psychiatry]. PMID- 20310089 TI - Rheumatism and So-Called Chronic Rheumatism. PMID- 20310090 TI - The Ancient Foundations of Heredity. PMID- 20310091 TI - The Association of Malignant Disease of the Thyroid and Multiple Lipomata. PMID- 20310092 TI - Ehrlich-Hata Remedy for Syphilis. PMID- 20310093 TI - Early Diagnosis of Pulmonary Tuberculosis. PMID- 20310094 TI - X-Rays With Bismuth Test Meal in Diagnosis of Gastric Conditions. PMID- 20310095 TI - Official Notice. PMID- 20310096 TI - Maritime Medical News. PMID- 20310098 TI - Queen's and the Carnegie Report. PMID- 20310097 TI - Reciprocity in Teaching. PMID- 20310099 TI - Halifax Medical College. PMID- 20310100 TI - Style in Medical Writing. PMID- 20310101 TI - Caisson-Disease in Canada. PMID- 20310102 TI - Editorial Notes. PMID- 20310104 TI - Some recent papers on Cardio-Vascular Conditions. PMID- 20310103 TI - The New Treatment of Syphilis. PMID- 20310105 TI - Personal. PMID- 20310106 TI - Surgical Treatment of Gastric and Duodenal Haemorrhage. PMID- 20310107 TI - Exophthalmic Goitre. PMID- 20310108 TI - On Death and Disability Resulting from Childbirth. PMID- 20310109 TI - Two Cases of Typhoid Spine. PMID- 20310110 TI - Origin of Urinary Stone. PMID- 20310112 TI - Canadian Medicine. PMID- 20310111 TI - Sarcoma of the Lung. PMID- 20310113 TI - The Ontario Medical Council. PMID- 20310114 TI - Medical Education. PMID- 20310115 TI - Medical Inspection of Schools. PMID- 20310116 TI - Reporting Cases of Tuberculosis. PMID- 20310117 TI - Freedom in Practice. PMID- 20310118 TI - Postpartum Haemorrhage. PMID- 20310119 TI - Obstetrics and Gynaecology. PMID- 20310120 TI - Army Medical Service. PMID- 20310121 TI - Personal. PMID- 20310122 TI - Malignant Disease in the Neck. PMID- 20310123 TI - Experiences with "606": A Preliminary Report. PMID- 20310124 TI - Tuberculin in the Diagnosis of Tuberculosis. PMID- 20310125 TI - Food Standards. PMID- 20310126 TI - The Inflammatory "Pelvic Mass". PMID- 20310127 TI - Cerebral Meningocele. PMID- 20310128 TI - Operation for Pott's Disease of the Spine. PMID- 20310129 TI - A Vision Realized. PMID- 20310130 TI - Hospital Troubles in Halifax. PMID- 20310131 TI - Expert Evidence. PMID- 20310132 TI - Teaching by Pantomime. PMID- 20310134 TI - Government Laboratories. PMID- 20310133 TI - Railways and Typhoid. PMID- 20310135 TI - The Journal and the Profession. PMID- 20310136 TI - Physical Education. PMID- 20310137 TI - Human and Bovine Tuberculosis. PMID- 20310138 TI - RETROSPECT OF SURGERY. PMID- 20310139 TI - Personal. PMID- 20310140 TI - A STUDY OF EIGHT HUNDRED AND FIFTY CASES OF SCARLET FEVER WITH A MORE PARTICULAR CONSIDERATION OF SEVENTY-ONE FATAL CASES: Part I. PMID- 20310141 TI - SOME CONSIDERATIONS IN DUODENAL ULCER. PMID- 20310142 TI - HUMAN CARRIERS OF DISEASE. PMID- 20310143 TI - MOUNTING MOIST SPECIMENS. PMID- 20310144 TI - SOCIAL PROBLEMS IN RELATION TO MEDICINE. PMID- 20310145 TI - MISSED ABORTION. PMID- 20310146 TI - A RUPTURED ECTOPIC GESTATION, OCCURRING IN THE THIRD WEEK OF TYPHOID FEVER, AND COMPLICATED BY TYPHOID PERFORATION OF THE ILEUM; OPERATION AND RECOVERY. PMID- 20310147 TI - Editorial. PMID- 20310148 TI - Res Judicatae. PMID- 20310149 TI - Retrospect of Surgery: L'anastomose Arterio-Veineuse. PMID- 20310150 TI - Army Medical Service: Canadian Army Medical Service. PMID- 20310151 TI - Personal. PMID- 20310152 TI - A STUDY OF EIGHT HUNDRED AND FIFTY CASES OF SCARLET FEVER WITH A MORE PARTICULAR CONSIDERATION OF SEVENTY-ONE FATAL CASES: Part II. PMID- 20310153 TI - THE RELATION OF THE THYROID GLAND TO THE FEMALE GENERATIVE ORGANS. PMID- 20310154 TI - MEDICAL INSPECTION OF SCHOOLS: REPORT TO THE CANADIAN MEDICAL ASSOCIATION. PMID- 20310155 TI - ACUTE TOXAEMIA: WAS COCAINE OR ADRENALIN THE CAUSE? PMID- 20310156 TI - NOTIFICATION OF TUBERCULOSIS. PMID- 20310158 TI - Res Judicatae. PMID- 20310157 TI - Editorial. PMID- 20310159 TI - Retrospect of Medicine. PMID- 20310160 TI - Personal. PMID- 20310161 TI - THE PRESENT STATUS OF CONSERVATIVE GYNAECOLOGY. PMID- 20310162 TI - TREATMENT OF TYPHOID FEVER BY VACCINES. PMID- 20310163 TI - TYPHOID IN THE WINNIPEG GENERAL HOSPITAL. PMID- 20310164 TI - AN UNCLASSIFIED TROPICAL FEVER. PMID- 20310165 TI - OBLITERATION OF THORACIC CAVITIES: (Experimental). PMID- 20310166 TI - A NEW ANTERIOR URETHROSCOPE. PMID- 20310167 TI - EXOPHTHALMIC GOITRE AND PREGNANCY. PMID- 20310168 TI - THE LATENT TETANY OF LACTATION. PMID- 20310169 TI - Editorial. PMID- 20310170 TI - Res Judicatae: A New Theory of Shock. PMID- 20310171 TI - Retrospect of Surgery. PMID- 20310172 TI - CANADIAN MEDICAL ASSOCIATION: President's Address. PMID- 20310173 TI - ADDRESS IN SURGERY. PMID- 20310174 TI - SCARLET FEVER: Preliminary Note of its Specific Microorganism. PMID- 20310175 TI - Editorial. PMID- 20310176 TI - Personal. PMID- 20310178 TI - TYPHOID BACILLUS CARRIERS. PMID- 20310177 TI - ON A CHRONIC CHOLERA CARRIER. PMID- 20310179 TI - INFANTILE MORTALITY IN CANADA. PMID- 20310180 TI - TYPHOID FEVER AT OTTAWA: January 1st-March 18th, 1911. PMID- 20310181 TI - THE FORT WILLIAM EPIDEMIC OF TYPHOID FEVER IN 1906. PMID- 20310182 TI - A LOCAL TYPHOID EPIDEMIC AT MURRAY BAY, P.Q. PMID- 20310183 TI - ACUTE VOLVULUS OF THE SMALL INTESTINE RESECTION: RECOVERY. PMID- 20310184 TI - INTESTINAL OBSTRUCTIONS DUE TO MECKEL'S DIVERTICULUM. PMID- 20310185 TI - Editorial. PMID- 20310186 TI - Res Judicatae: Stammering. PMID- 20310187 TI - Retrospect of Surgery: A Generation of Surgery. PMID- 20310188 TI - Personal. PMID- 20310189 TI - CANCER OF THE STOMACH: WITH SPECIAL REFERENCE TO ITS RELATIONSHIP TO GASTRIC ULCER AND THE ADVANTAGE OF A TWO-STAGE OPERATION. PMID- 20310191 TI - EXTIRPATION OF THE THYROID GLAND IN MONKEYS. PMID- 20310190 TI - THE AETIOLOGY OF CHOLELITHIASIS, WITH SPECIAL REFERENCE TO THE AGE-INCIDENCE. PMID- 20310192 TI - GRADUATED DILATATION OF THE URETEROVESICAL ORIFICE AND THE URETER ABOVE IT. PMID- 20310193 TI - MODERN AIDS TO DIAGNOSIS IN OTOLOGY AND THEIR SIGNIFICANCE. PMID- 20310194 TI - THE SURGICAL TREATMENT OF GALL-STONE DISEASE. PMID- 20310195 TI - PRIMARY TUMOURS OF THE BLADDER. PMID- 20310196 TI - TUBERCULOUS OSTEOMYELITIS OF THE SYMPHYSIS PUBIS. PMID- 20310197 TI - Editorial. PMID- 20310198 TI - CANADIAN MEDICAL ASSOCIATION. PMID- 20310199 TI - Retrospect of Medicine: The Fringes of the Cancer Problem. PMID- 20310201 TI - Personal. PMID- 20310200 TI - Retrospect of Surgery. PMID- 20310202 TI - Army Medical Service. PMID- 20310203 TI - Personal. PMID- 20310204 TI - TRANSIENT ATTACKS OF APHASIA AND PARALYSES IN STATES OF HIGH BLOOD PRESSURE AND ARTERIO-SCLEROSIS. PMID- 20310205 TI - THE NON-OPERATIVE TREATMENT OF APPENDICITIS. PMID- 20310206 TI - I.-PERITONEAL EFFUSION (ASCITES) IN TYPHOID FEVER II.-THE PHYSICAL SIGNS OF EXUDATE IN THE PERITONEAL CAVITY. PMID- 20310207 TI - PROLONGED PREGNANCY. PMID- 20310208 TI - THE DIAGNOSIS OF SYPHILIS BY THE BINDING OF COMPLEMENT METHOD: FURTHER EXPERIENCE IN THE USE OF THE AUTHOR'S MODIFICATION. PMID- 20310209 TI - HYDATID MOLE. ITS RELATION TO CHORIOEPITHELIOMA AND CYSTIC DEGENERATION OF THE OVARIES. WITH REPORT OF TWO CASES COMPLICATED WITH ECLAMPSIA. PMID- 20310211 TI - Editorial. PMID- 20310210 TI - A RARE SARCOMA. PMID- 20310212 TI - Retrospect of Medicine. PMID- 20310213 TI - THE PREVENTION OF INSANITY. PMID- 20310214 TI - THE OPERATIVE TREATMENT OF GLAUCOMA WITH SPECIAL REFERENCE TO THE LAGRANGE METHOD. PMID- 20310215 TI - THE STATISTICS OF INFANTILE PARALYSIS. PMID- 20310216 TI - THE SURGEON'S INTEREST IN HENOCH'S PURPURA. PMID- 20310217 TI - TREATMENT OF UTERINE DISPLACEMENTS. PMID- 20310218 TI - TRAUMATIC LESIONS OF THE CORD WITHOUT INJURY TO THE SPINAL COLUMN. PMID- 20310219 TI - ECLAMPSIA. PMID- 20310220 TI - THE SURGICAL TREATMENT OF ANTERIOR POLIOMYELITIS. PMID- 20310221 TI - PROSTATECTOMY: THE SUPRAPUBIC ROUTE. PMID- 20310222 TI - COMPLETE INVERSION OF THE UTERUS RELIEVED BY ABDOMINAL OPERATION. PMID- 20310223 TI - Editorial. PMID- 20310224 TI - Retrospect of Surgery. PMID- 20310226 TI - Personal. PMID- 20310225 TI - Res Judicatae: Bronchial Asthma. PMID- 20310228 TI - ADDRESS IN GYNAECOLOGY: Mistakes in Diagnosis and Treatment. PMID- 20310227 TI - INAUGURAL ADDRESS: Delivered Before the Faculty of Medicine in the University of Toronto, October 3rd, 1911. PMID- 20310229 TI - SANITARY MILK. PMID- 20310230 TI - AN EXPERIMENTAL STUDY OF THE PHAGOCYTIC IMMUNITY PRODUCED BY TUBERCULIN. PMID- 20310231 TI - PRIMARY PYELITIS IN INFANTS. PMID- 20310232 TI - MOULDS IN THE ALIMENTARY CANAL. PMID- 20310233 TI - LUNG ABSCESS. PMID- 20310234 TI - A NEW COMBINED EXAMINING AND OPERATING AIR DISTENTION ENDOSCOPE. PMID- 20310235 TI - ON THE USE OF RADIUM IN OPHTHALMOLOGY. PMID- 20310236 TI - A SIMPLE METHOD OF TREATING FRACTURED CLAVICLE. PMID- 20310238 TI - Editorial. PMID- 20310237 TI - MALIGNANT OEDEMA. PMID- 20310239 TI - Retrospect of Medicine. PMID- 20310240 TI - UNDERGRADUATE TRAINING AND REQUIREMENTS FOR LICENSE TO PRACTICE. PMID- 20310241 TI - PSEUDO-MUSCULAR HYPERTROPHY. PMID- 20310242 TI - OBSERVATIONS FROM BOER-LAND. PMID- 20310243 TI - SEMMELWEISS AND HOLMES. PMID- 20310244 TI - OMENTAL CYSTS. PMID- 20310245 TI - Editorial. PMID- 20310246 TI - Res Judicatae: Conservation of the Ovary. PMID- 20310247 TI - Retrospect of Medicine. PMID- 20310248 TI - Retrospect of Surgery. PMID- 20310249 TI - BACILLUS LEPRAE IN THE NASAL MUCOUS MEMBRANE. PMID- 20310250 TI - ON THE AMMONIA COEFFICIENT IN A CASE OF SEVERE VOMITING IN PREGNANCY. PMID- 20310251 TI - ANGIOMA OF THE LARYNX. PMID- 20310252 TI - BIOLOGICAL PRODUCTS. PMID- 20310253 TI - SOME OBSERVATIONS ON CHRONIC MYOCARDITIS. PMID- 20310254 TI - MELAENA. PMID- 20310255 TI - Editorial. PMID- 20310256 TI - Res Judicatae: Present Knowledge of Duodenal Ulcer. PMID- 20310257 TI - Retrospect of Medicine. PMID- 20310258 TI - Retrospect of Laryngology. PMID- 20310259 TI - THE CHEMICAL BASIS OF LIFE. PMID- 20310260 TI - LUETIC CIRRHOSIS OF THE LIVER. PMID- 20310261 TI - LOW PERCENTAGES IN INFANT FEEDING. PMID- 20310262 TI - PULMONARY TUBERCULOSIS. PMID- 20310263 TI - THE DIFFICULTIES IN PROGNOSIS IN PULMONARY TUBERCULOSIS. PMID- 20310264 TI - THE SURGICAL ASPECT OF DUODENAL ULCER. PMID- 20310265 TI - A CASE OF ACCIDENTAL EXTRA GENITAL SYPHILIS. PMID- 20310266 TI - CHRONIC COLITIS. PMID- 20310267 TI - CHONDRODYSTROPHY. PMID- 20310268 TI - EPITHELIOMA OF THE PHARYNX. PMID- 20310269 TI - Editorial. PMID- 20310270 TI - Res Judicatae: Lord Lister. PMID- 20310271 TI - THE ESTABLISHMENT OF TREPONEMA PALLIDUM AS THE CAUSATIVE AGENT OF SYPHILIS, AND THE CULTURAL DIFFERENTIATION BETWEEN THIS ORGANISM AND CERTAIN MORPHOLOGICALLY ALLIED SPIROCHAETAE. PMID- 20310273 TI - GASTRIC CARCINOMA. PMID- 20310272 TI - SALVARSAN: A YEAR'S EXPERIENCE: REPORT OF TWO HUNDRED AND FIFTY CASES. PMID- 20310274 TI - CLINICAL AND PATHOLOGICAL NOTES UPON CERTAIN SUB-TROPICAL DISEASES. PMID- 20310276 TI - THE INTRAPERITONEAL ROUTE IN OPERATIONS ON THE URETERS. PMID- 20310275 TI - SOME PHYSIOLOGICAL ASPECTS OF REFERRED PAIN. PMID- 20310277 TI - Editorial. PMID- 20310278 TI - Retrospect of Surgery. PMID- 20310279 TI - INFLAMMATORY CYSTS AND CANCER OF THE BREAST. PMID- 20310280 TI - SOME ACUTE ABDOMINAL EMERGENCIES. PMID- 20310281 TI - DISINFECTION IN AND AFTER INFECTIOUS DISEASES. PMID- 20310282 TI - THE PRESENT STATUS OF THE WASSERMANN REACTION. PMID- 20310283 TI - TABES DORSALIS: THE EXHAUSTION THEORY WITH EXPERIMENTAL EVIDENCE. PMID- 20310284 TI - BRONCHOSCOPY. PMID- 20310285 TI - Editorial. PMID- 20310286 TI - Res Judicatae: The Recognition of Pulmonary Tuberculosis. PMID- 20310288 TI - THE EFFECT OF ANATOMICAL AND IMMUNOLOGICAL DATA UPON OUR CONCEPTION OF THE TUBERCULOUS. PMID- 20310287 TI - Retrospect of Medicine: Human and Bovine Tuberculosis. PMID- 20310289 TI - OUR PRESENT ATTITUDE TOWARDS TUBERCULOSIS. PMID- 20310290 TI - HOUSING CONDITIONS IN CANADA. PMID- 20310291 TI - RHEUMATISM IN THE CHILDREN OF VANCOUVER AND DISTRICT. PMID- 20310292 TI - PERSONAL REMINISCENCES OF LISTER. PMID- 20310293 TI - INTERESTING CASE OF ATTEMPTED SUICIDE IN THE CANTON HOSPITAL. PMID- 20310294 TI - Editorial. PMID- 20310295 TI - Res Judicatae. PMID- 20310296 TI - Retrospect of Surgery. PMID- 20310297 TI - DOES CHOLECYSTENTEROSTOMY DIVERT THE FLOW OF BILE FROM THE COMMON DUCT? PMID- 20310298 TI - LABORATORY TESTS IN THE DIAGNOSIS OF GENERAL PARESIS. PMID- 20310299 TI - THE BONE-MARROW, A STUDY FROM THE STANDPOINT OF THE CLINICAL PATHOLOGIST. PMID- 20310300 TI - PRESIDENTIAL ADDRESS. PMID- 20310301 TI - ANOMALY OF THE VAGINA AND UTERUS. PMID- 20310302 TI - Editorial. PMID- 20310303 TI - Res Judicatae: The Conservative Treatment of Suppurative Otitis Media. PMID- 20310304 TI - TREATMENT OF THE FRACTURES OF THE LONG BONES. PMID- 20310305 TI - LABYRINTH TESTS. PMID- 20310306 TI - PLEURISY IN CHILDREN. PMID- 20310307 TI - OBSERVATIONS RELATING TO DIET IN TUBERCULOSIS. PMID- 20310308 TI - REVOLVER BULLET IN THE CHIASMA: CONSECUTIVE BINOCULAR BLINDNESS. PMID- 20310309 TI - DOES A HUMAN TICK-BORNE DISEASE EXIST IN BRITISH COLUMBIA? PMID- 20310310 TI - SOME EXPERIENCES WITH RADIUM. PMID- 20310311 TI - [Not Available]. PMID- 20310312 TI - Editorial. PMID- 20310313 TI - Res Judicatae: A Medical Missionary. PMID- 20310314 TI - Retrospect of Surgery. PMID- 20310315 TI - ADDRESS IN SURGERY. PMID- 20310316 TI - TYPHOID PLEURISY. PMID- 20310317 TI - DEEP INJECTIONS OF ALCOHOL FOR TRIFACIAL NEURALGIA-ONE HUNDRED AND TWO CASES. PMID- 20310318 TI - THE ACTION OF DRUGS ON THE UTERUS. PMID- 20310319 TI - A REPORT OF TWO CASES OF TYPHOID FEVER WHICH SHOW UNCOMMON LESIONS DUE TO THE BACILLUS TYPHOSUS: 1. ACUTE PURULENT PERICARDITIS 2. ACUTE HAEMORRHAGIC PLEURITIS. PMID- 20310320 TI - REPORT OF TWO CASES OF ABDOMINAL SURGERY. PMID- 20310321 TI - A CASE OF ACUTE FAT NECROSIS; OPERATION; RECOVERY. PMID- 20310322 TI - Editorial. PMID- 20310323 TI - Res Judicatae: The Exploratory Puncture. PMID- 20310324 TI - Retrospect of Surgery. PMID- 20310325 TI - THE THERAPEUTICS OF TO-DAY. PMID- 20310326 TI - DIABETES MELLITUS. PMID- 20310327 TI - TRAUMATIC ARTHRITIS OF THE KNEE AND ITS EFFECTS. PMID- 20310328 TI - RADIUM AND AGE. PMID- 20310330 TI - Editorial. PMID- 20310329 TI - SEROUS MENINGITIS, CHOKED DISC AND MULTIPLE POLYNEURITIS OF CRANIAL NERVES IN A CASE OF A YOUNG ALCOHOLIC SMOKER. PMID- 20310331 TI - Res Judicatae: On the Balance of the Bases, Sodium, Potassium and Calcium in the Body. A Review of some Recent Papers. PMID- 20310332 TI - Retrospect of Obstetrics. PMID- 20310333 TI - Retrospect of Surgery. PMID- 20310335 TI - Editorial. PMID- 20310334 TI - A FURTHER CONTRIBUTION TO THE STUDY OF SCOLIOSIS. PMID- 20310336 TI - Res Judicatae: Medical Education in Europe. PMID- 20310337 TI - Retrospect of Medicine: Vaccination as a Preventive and Therapeutic Measure in Typhoid Fever. PMID- 20310338 TI - "UNTO THE THIRD AND FOURTH GENERATION:" A STUDY IN EUGENICS. PMID- 20310339 TI - DISPLACED AND MOVABLE KIDNEY IN WOMEN: ITS SYMPTOMATOLOGY, DIAGNOSIS, AND TREATMENT. PMID- 20310340 TI - A NEW REAGENT FOR DETECTING OCCULT BLOOD. PMID- 20310341 TI - FACTORS FREQUENTLY OVERLOOKED IN THE EARLY DIAGNOSIS OF PULMONARY TUBERCULOSIS. PMID- 20310342 TI - THE TREATMENT OF ROTO-LATERAL CURVATURE OF THE SPINE. PMID- 20310343 TI - INTERNAL HERNIA: WITH A REPORT OF A CASE OF MESOCOLIC HERNIA. PMID- 20310344 TI - THE HEART DURING SOME ACUTE INFECTIONS. PMID- 20310346 TI - THE TREATMENT OF NAEVUS WITH SOLID CARBON DIOXIDE. PMID- 20310345 TI - A SERIES OF CASES OF SMALL-POX, WITH SOME REMARKS ON DIAGNOSIS AND VACCINATION. PMID- 20310347 TI - TICK BITE IN BRITISH COLUMBIA. PMID- 20310349 TI - Editorial. PMID- 20310348 TI - HEMIPLEGIA IN TYPHOID FEVER. PMID- 20310350 TI - Res Judicatae. PMID- 20310351 TI - Retrospect of Surgery. PMID- 20310352 TI - SURGICAL TREATMENT OF EXOPHTHALMIC GOITRE. PMID- 20310353 TI - A CASE OF HAEMOLYTIC JAUNDICE WITH SPLENOMEGALY. PMID- 20310354 TI - THE STANDARDIZATION OF DISINFECTANTS. PMID- 20310355 TI - THE OPERATIVE TREATMENT OF CLEFT PALATE. PMID- 20310356 TI - THE RESULTS OF TREATMENT OF SYPHILIS AS SHOWN BY THE WASSERMANN REACTION. PMID- 20310357 TI - AN APPARATUS FOR CONTINUOUS ASPIRATION. PMID- 20310359 TI - Editorial. PMID- 20310358 TI - SUCCESSFUL CATARACT OPERATION ON A PATIENT AGED NINETY-TWO YEARS. PMID- 20310360 TI - Res Judicatae: Sir William Gairdner. PMID- 20310361 TI - THE TOXIC EFFECTS OF GASOLINE FUMES. PMID- 20310362 TI - Editorial. PMID- 20310363 TI - Retrospect of Medicine. PMID- 20310364 TI - SOME OBSERVATIONS ON THE DIAGNOSIS AND TREATMENT OF SUBACUTE AND CHRONIC PANCREATITIS. PMID- 20310365 TI - THE NATURE OF SURGICAL SHOCK WITH SOME REMARKS ON ITS TREATMENT. PMID- 20310366 TI - PROSTATECTOMY-SUSPENSION OF THE BLADDER. PMID- 20310367 TI - PENALTIES OF LATE DIAGNOSIS OF DISEASES OF THE URINARY TRACT. PMID- 20310368 TI - THE FALLACIES OF EXISTING FATALITY RATES. PMID- 20310369 TI - MUNICIPAL HEALTH WORK PERTAINING TO INFANT WELFARE. PMID- 20310370 TI - CEREBELLAR ABSCESS OF OTITIC ORIGIN, OPERATION -RECOVERY. PMID- 20310371 TI - SILVER STYLE IN THE NASAL DUCT-REMOVAL AFTER FORTY YEARS. PMID- 20310372 TI - Editorial. PMID- 20310374 TI - Res Judicatae: Artificial Pneumothorax in the Treatment of Pulmonary Tuberculosis. PMID- 20310373 TI - THE DIAGNOSIS OF SMALLPOX. PMID- 20310375 TI - Retrospect of Surgery: Pyelonephritis and the Pyelitis of Pregnancy. PMID- 20310376 TI - SOME CLINICAL OBSERVATIONS ON ARTERIO-SCLEROSIS. PMID- 20310377 TI - THREE CASES OF ACROMEGALY WITH ONE AUTOPSY. PMID- 20310378 TI - ABDOMINAL INJURIES. PMID- 20310379 TI - MARCHING. PMID- 20310380 TI - Editorial. PMID- 20310381 TI - Res Judicatae: Blood Pressure in Life Insurance. PMID- 20310382 TI - SEVENTEENTH INTERNATIONAL CONGRESS OF MEDICINE. PMID- 20310383 TI - THE SURGICAL TREATMENT OF PENDULOUS ABDOMEN. PMID- 20310384 TI - SALVARSAN IN THE TREATMENT OF SYPHILITIC DISEASES OF THE CENTRAL NERVOUS SYSTEM. PMID- 20310385 TI - MILK AND MEAT INSPECTION. PMID- 20310386 TI - LIPOSIS PANCREATICA. PMID- 20310388 TI - Editorial. PMID- 20310387 TI - PRIMARY MALIGNANT NEOPLASM OF THE FALLOPIAN TUBE. PMID- 20310389 TI - THE DIAGNOSIS OF SMALLPOX. PMID- 20310390 TI - Retrospect of Surgery. PMID- 20310391 TI - Res Judicatae: The Earliest Recognition of Appendicitis. PMID- 20310392 TI - PUNCTURE OF THE CORPUS CALLOSUM. PMID- 20310393 TI - SOME RECENT WORK ON ACCESSORY FACTORS IN NUTRITION. PMID- 20310394 TI - TUBERCULOSIS OF THE GENITO-URINARY SYSTEM FROM THE GENERAL PRACTITIONER'S STAND POINT. PMID- 20310396 TI - Editorial. PMID- 20310395 TI - TUBERCULOUS APPENDICITIS. PMID- 20310397 TI - Res Judicatae: On the Colon and Ileocolotomy. PMID- 20310398 TI - Retrospect of Pathology. PMID- 20310399 TI - ADDRESS IN SURGERY : FRACTURES AND THEIR TREATMENT. PMID- 20310400 TI - CONGENITAL HYPERTROPHIC PYLORIC STENOSIS. PMID- 20310401 TI - SOME REMARKS ON ENDOCARDITIS IN INFLUENZA: REPORT OF A CASE. PMID- 20310402 TI - THE RESPONSIBILITY FOR THE ADVANCED CASE OF TUBERCULOSIS. PMID- 20310403 TI - NOTES ON TWO CASES OF INTESTINAL OBSTRUCTION. PMID- 20310404 TI - Editorial. PMID- 20310405 TI - Res Judicatae. PMID- 20310406 TI - THE CLINICAL SIGNIFICANCE OF THE AUTONOMIC NERVES SUPPLYING THE VISCERA, AND THEIR RELATIONS TO THE GLANDS OF INTERNAL SECRETION. PMID- 20310407 TI - ADDRESS IN GYNAECOLOGY. PMID- 20310409 TI - THE DIAGNOSIS OF TUBERCULOUS BRONCHIAL AND MEDIASTINAL GLANDS. PMID- 20310408 TI - THE DIAGNOSIS AND TREATMENT OF ACUTE MASTOIDITIS. PMID- 20310411 TI - Editorial. PMID- 20310410 TI - FREE, SUPPURATIVE PERITONITIS DUE TO PYOSALPINX. PMID- 20310412 TI - Retrospect of Gynaecology: Treatment of Uterine Fibroids by X-Rays. PMID- 20310413 TI - Res Judicatae: The Results of the Friedmann Treatment. PMID- 20310414 TI - PITUITARY EXTRACT IN OBSTETRICAL PRACTICE. PMID- 20310415 TI - INTUSSUSCEPTION, ITS DIAGNOSIS AND TREATMENT, WITH A REPORT OF SEVEN CASES. PMID- 20310416 TI - INSANITY AND ITS RELATION TO THE STATE. PMID- 20310417 TI - PAIN AS A SYMPTOM IN PULMONARY TUBERCULOSIS. PMID- 20310418 TI - RETROPERITONEAL HAEMOTOMA AS A CAUSE OF INTESTINAL OBSTRUCTION. PMID- 20310419 TI - MEDIASTINAL ABSCESS. PMID- 20310420 TI - TORSION OF THE CAECUM, ASCENDING AND HALF OF THE TRANSVERSE COLON; WITH OPERATION AND RECOVERY. PMID- 20310421 TI - Editorial. PMID- 20310422 TI - MEDICAL COUNCIL OF CANADA: First Announcement, July 1st, 1913. PMID- 20310423 TI - Res Judicatae: The Public Health Act of Ontario. PMID- 20310424 TI - REPORT OF A SERIES OF ABDOMINAL CAESAREAN SECTIONS. PMID- 20310425 TI - A NEW AND RATIONAL METHOD FOR THE STUDY OF THE FUNCTIONAL DISEASES OF THE NERVOUS SYSTEM. PMID- 20310426 TI - THE TREATMENT OF TUBERCULAR SPONDYLITIS OR POTT'S DISEASE. PMID- 20310427 TI - THE RUNNING SUTURE-AND THE BLOODLESS OPERATION. PMID- 20310428 TI - CLINICAL ASPECTS OF THE REGENERATION OF BONE, AS MANIFESTED BY A STUDY OF THE UNION OF FRACTURES. PMID- 20310429 TI - AN EPIDEMIC OF JAUNDICE. PMID- 20310431 TI - Editorial. PMID- 20310430 TI - CONGENITAL CARDIAC DISEASE. PMID- 20310432 TI - Res Judicatae: Graves' Disease. PMID- 20310433 TI - Res Judicatae: Veterinary Education. PMID- 20310434 TI - THOMAS SYDENHAM, THE ENGLISH HIPPOCRATES: (1624-1689). PMID- 20310435 TI - SOME PSYCHIATRIC PROBLEMS FROM THE GENERAL PRACTITIONER'S STANDPOINT. PMID- 20310436 TI - ON THE RELATIONSHIP BETWEEN TUMOURS PROPER (BLASTOMAS) AND HYPERBLASTOSIS. PMID- 20310437 TI - NOTES ON HUNTINGTON'S CHOREA. PMID- 20310438 TI - DISEASES OF THE THYROID GLAND VIEWED FROM THE STANDPOINT OF THE SURGEON. PMID- 20310439 TI - A CASE OF MASTOIDITIS WITH PERISINUS ABSCESS AND PARALYSIS OF ONE LEG. PMID- 20310440 TI - Editorial. PMID- 20310441 TI - DISEASES OF THE STOMACH. PMID- 20310443 TI - PYLORIC SPASM. PMID- 20310442 TI - RETENTION OF THE GASTRIC CONTENTS. PMID- 20310444 TI - ON SOME CLINICAL ASPECTS OF GASTRIC DISEASE. PMID- 20310445 TI - FRONTAL TUMOURS. PMID- 20310446 TI - A BONE STAPLE-PLATE. PMID- 20310448 TI - Res Judicatae: The Present Status of Surgery in Pulmonary Tuberculosis. PMID- 20310447 TI - Editorial. PMID- 20310449 TI - THE MEDICAL TREATMENT OF CHOLELITHIASIS. PMID- 20310450 TI - GASTRIC HYPERACIDITY. PMID- 20310451 TI - THE PERIOSTEUM. PMID- 20310452 TI - Case Reports: A CASE ILLUSTRATING DUCTLESS GLAND RELATIONSHIP. PMID- 20310454 TI - MEDICAL INSPECTION OF SCHOOLS. PMID- 20310453 TI - THE COLLEGE OF SURGEONS. PMID- 20310455 TI - INTESTINAL STASIS. PMID- 20310456 TI - OTTAWA AND TYPHOID. PMID- 20310457 TI - TYPHOID FEVER AT HALIFAX. PMID- 20310458 TI - MANITOBA MEDICAL COLLEGE. PMID- 20310460 TI - Retrospect of Surgery. PMID- 20310459 TI - Res Judicatae: ACIDOSIS. PMID- 20310461 TI - SYPHILITIC INFECTIONS OF THE CENTRAL NERVOUS SYSTEM. PMID- 20310462 TI - CONCERNING THE IMMUNITIES OF TOLERANCE: A PRELIMINARY COMMUNICATION. PMID- 20310463 TI - SYMPTOMS AND TREATMENT OF HYPERTHYROIDISM. PMID- 20310464 TI - SMALLPOX AND CHICKEN-POX. PMID- 20310466 TI - THE SOCIETY OF AMERICAN BACTERIOLOGISTS. PMID- 20310465 TI - THE NEW QUACKERY. PMID- 20310467 TI - RECIPROCITY. PMID- 20310468 TI - THE LARYNGOLOGISTS. PMID- 20310469 TI - Retrospect of Medicine: RECENT ADVANCES IN TROPICAL MEDICINE. PMID- 20310470 TI - THE TRIPLE ALLIANCE: HEART, KIDNEY, AND ARTERIAL DISEASE. PMID- 20310471 TI - HYPERTROPHY OF THE FAUCIAL TONSIL AND ITS TREATMENT. PMID- 20310472 TI - PRIMARY ENDOTHELIOMA OF THE PLEURA. PMID- 20310474 TI - SEPTIC PUERPERAL INFECTION, DIAGNOSIS AND TREATMENT. PMID- 20310473 TI - THE TREATMENT OF TABES DORSALIS AND GENERAL PARESIS WITH SALVARSAN. PMID- 20310475 TI - LOOSE BODIES IN THE KNEE-JOINT. PMID- 20310476 TI - A VICIOUS SYSTEM. PMID- 20310477 TI - DR. SHEPHERD'S RETIREMENT. PMID- 20310478 TI - MONTREAL'S PERIL. PMID- 20310479 TI - THE LAURENTIAN SOCIETY. PMID- 20310480 TI - SUPRAPUBIC PROSTATECTOMY. PMID- 20310481 TI - THE PRESENT POSITION OF VENESECTION. PMID- 20310482 TI - GASTRO-ENTEROSTOMY; EXPERIMENTAL AND CLINICAL. PMID- 20310483 TI - Case Reports: TRANSVERSE PRESENTATION WITH UNUSUAL SEQUELAE. PMID- 20310484 TI - PROVINCIAL ASSOCIATIONS. PMID- 20310486 TI - ANTITYPHOID VACCINATION. PMID- 20310485 TI - INTRAPROVINCIAL AFFILIATION. PMID- 20310487 TI - Res Judicatae: CHLORIDE AND UREA RETENTION IN NEPHRITIS. PMID- 20310488 TI - AUTO-INFECTION ASSOCIATED WITH THE INTESTINAL CANAL. PMID- 20310489 TI - ACIDOSIS. PMID- 20310490 TI - THE MENTALLY DEFECTIVE. PMID- 20310491 TI - ON THE DESTRUCTION OF SEBACEOUS GLANDS, SWEAT GLANDS, AND HAIR FOLLICLES, AND THE DISEASES THEREBY CURED. PMID- 20310492 TI - Case Reports: A CASE OF PERSISTENT ENURESIS. PMID- 20310493 TI - THE TRAGEDY OF OLD AGE. PMID- 20310494 TI - THE SURGEON-GENERAL'S LIBRARY. PMID- 20310495 TI - PUBLIC HEALTH IN MONTREAL. PMID- 20310496 TI - CANADIAN MEDICAL ASSOCIATION. PMID- 20310497 TI - THE DEVELOPMENT OF OBSTETRICS. PMID- 20310498 TI - HAEMORRHAGIC DISEASES. PMID- 20310499 TI - THE PRESENT STATUS OF THE ROENTGEN EXAMINATION IN THE DIAGNOSIS OF GASTRIC ULCER. PMID- 20310500 TI - TRAUMATIC ASPHYXIA WITH A REPORT OF SIX CASES. PMID- 20310502 TI - AN ARMY SURGEON. PMID- 20310501 TI - Case Reports: FOUR CASES OF THROMBOSIS OF THE LATERAL SINUS WITH RECOVERY. PMID- 20310503 TI - WORKMEN'S COMPENSATION IN ONTARIO. PMID- 20310504 TI - ONTARIO AFFILIATION. PMID- 20310505 TI - THE METHOD OF ZADIG IN THE PRACTICE OF MEDICINE. PMID- 20310506 TI - THE TREATMENT OF PUERPERAL INFECTIONS. PMID- 20310507 TI - THE DIAGNOSIS OF SUBTENTORIAL TUMOURS: WITH A REPORT OF FOUR CASES. PMID- 20310508 TI - NICKEL-CHROMIUM WIRE FOR THE BACTERIOLOGICAL LABORATORY. PMID- 20310509 TI - NERVE ANASTOMOSIS. PMID- 20310511 TI - THE PRESIDENT'S ADDRESS. PMID- 20310510 TI - CHLOROMA. PMID- 20310512 TI - THE ADDRESS IN MEDICINE. PMID- 20310513 TI - THE PENITENTIARY. PMID- 20310515 TI - SITTING UPON THE WALL. PMID- 20310514 TI - MAKING MONTREAL DRINK SEWAGE. PMID- 20310516 TI - Res Judicatae: EMERODS, MICE AND THE PLAGUE OF I SAMUEL VI. PMID- 20310517 TI - ONTARIO COUNTY MEDICAL HEALTH OFFICERS. PMID- 20310518 TI - WINNIPEG GENERAL HOSPITAL. PMID- 20310519 TI - SOCIETIES FOR MENTAL HYGIENE. PMID- 20310520 TI - MANITOBA MEDICAL ASSOCIATION. PMID- 20310521 TI - ONTARIO MEDICAL ASSOCIATION. PMID- 20310522 TI - THE RELATION OF THEORY AND PRACTICE IN THE OPERATIVE TREATMENT OF GENITAL PROLAPSE. PMID- 20310523 TI - SURGICAL TEACHING. PMID- 20310525 TI - CARDIAC HYPERTROPHY. PMID- 20310524 TI - INFANT MORTALITY. PMID- 20310526 TI - THE ST. JOHN MEETING. PMID- 20310527 TI - THE ADDRESS IN SURGERY. PMID- 20310528 TI - THE ADDRESS IN OBSTETRICS. PMID- 20310529 TI - SMALLPOX IN NEW SOUTH WALES. PMID- 20310530 TI - Res Judicatae: GIANTS AND DWARFS. PMID- 20310531 TI - THE MEDICAL PROFESSION AND THE MILITIA. PMID- 20310532 TI - THE TREATMENT OF EMPYEMA, SUBPHRENIC ABSCESS, ETC., BY ASPIRATION FOLLOWED BY INJECTION OF FORMALIN SOLUTION. PMID- 20310533 TI - LINITIS PLASTICA. PMID- 20310535 TI - INDUSTRIAL DISEASE AND INDUSTRIAL HYGIENE. PMID- 20310534 TI - HOUR-GLASS CONTRACTION OF THE STOMACH WITH REPORT OF THREE CASES. PMID- 20310536 TI - THE CANADIAN PRACTITIONER'S DIAGNOSIS OF PULMONARY TUBERCULOSIS. PMID- 20310538 TI - THE WAR. PMID- 20310537 TI - THE IMPORTANCE OF THE BALKAN WARS TO THE MEDICAL PROFESSION OF CANADA. PMID- 20310539 TI - THE ASSOCIATION. PMID- 20310540 TI - THE MEDICAL JOURNAL OF AUSTRALIA. PMID- 20310542 TI - THE PHYLACOGEN TREATMENT OF HAY FEVER. PMID- 20310541 TI - Res Judicatae: PARALYSIS AND TICK-BITE. PMID- 20310543 TI - VASCULAR CRISES AND ANGIOSPASM. PMID- 20310544 TI - PAROXYSMAL TACHYCARDIA WITH A REVIEW OF FOUR CASES. PMID- 20310545 TI - RECENT INVESTIGATIONS ON THE SEMICIRCULAR CANALS AND THEIR CLINICAL APPLICATIONS. PMID- 20310546 TI - THE MEDICAL PROFESSION OF ALBERTA AND THE DEFENCE OF THE COUNTRY. PMID- 20310547 TI - NATIONAL DEFENCE AND THE MEDICAL PROFESSION. PMID- 20310548 TI - ANTITYPHOID INOCULATION AT THE WINNIPEG GENERAL HOSPITAL. PMID- 20310549 TI - SUBTROCHANTERIC FRACTURE OF THE FEMUR. PMID- 20310550 TI - Case Reports: A CASE OF TETANUS, WITH RECOVERY, TREATED BY CARBOLIC ACID INJECTIONS. PMID- 20310551 TI - THE CANADIAN MEDICAL SERVICE. PMID- 20310552 TI - THE HOSPITAL AND WAR. PMID- 20310553 TI - THE MOMENT AND THE TELEPHONE. PMID- 20310554 TI - AN EXPERIMENT IN TYPHOID. PMID- 20310556 TI - HEROES AND HEROINES OF SCIENCE. PMID- 20310555 TI - Res Judicatae: PUBLIC HEALTH IN ONTARIO. PMID- 20310557 TI - ESSEX COUNTY MEDICAL SOCIETY. PMID- 20310558 TI - MONTREAL MEDICO-CHIRURGICAL SOCIETY. PMID- 20310559 TI - I-INTESTINAL STASIS. PMID- 20310560 TI - II-INTESTINAL STASIS. PMID- 20310561 TI - III-INTESTINAL STASIS. PMID- 20310562 TI - IV-INTESTINAL STASIS. PMID- 20310563 TI - V-INTESTINAL STASIS. PMID- 20310564 TI - VI-ILEAL STASIS. PMID- 20310565 TI - MEDICAL COUNCIL EXAMINATIONS. PMID- 20310566 TI - THE EARLY DIAGNOSIS AND PROGNOSIS OF PULMONARY TUBERCULOSIS BY ROENTGEN METHODS. PMID- 20310567 TI - THE SUBCUTANEOUS INJECTION OF OXYGEN. PMID- 20310569 TI - INTESTINAL STASIS. PMID- 20310568 TI - Case Reports: OBSTRUCTION OF THE JEJUNUM TWO FEET FROM ITS ORIGIN. PMID- 20310570 TI - IMPERIAL RECIPROCITY. PMID- 20310571 TI - THE WAR AND THE WOUNDED. PMID- 20310572 TI - THE VANCOUVER MEETING. PMID- 20310573 TI - THE SELECTION OF ANAESTHETICS, SEQUENCES AND METHODS. PMID- 20310574 TI - CHLOROFORM ANAESTHESIA. PMID- 20310575 TI - X-RAY EVIDENCES OF GASTRIC CARCINOMA. PMID- 20310576 TI - THE COMPLEMENT FIXATION TEST IN GONORRHOEA. PMID- 20310577 TI - INJURIES OF THE FOOT: WITH A NEW METHOD OF REDUCING DISLOCATION OF THE BIG TOE. PMID- 20310578 TI - THE PRENATAL CARE OF OBSTETRIC CASES. PMID- 20310579 TI - Case Reports: TUBERCULOSIS OF THE SPLEEN. PMID- 20310580 TI - THE LATE PROFESSOR MINES. PMID- 20310581 TI - THE WOUNDED. PMID- 20310582 TI - A LETTER FROM THE FRONT. PMID- 20310583 TI - MEDICAL ASSISTANCE IN OUTLYING DISTRICTS. PMID- 20310584 TI - Res Judicatae: HEALTH, INSURANCE AND THE MEDICAL PROFESSION. PMID- 20310585 TI - CANADIAN MEDICAL ASSOCIATION: PUBLIC HEALTH SECTION. PMID- 20310586 TI - The Liver in its Relation to Operations on the Biliary Tract and the Stomach. PMID- 20310587 TI - Some Elementary Features of the X-ray Diagnosis of Gastric Carcinoma, Gastric Ulcer and Duodenal Ulcer. PMID- 20310588 TI - Congenital Dislocation of the Hip. PMID- 20310589 TI - Observations on a Sporothrix Bearing some Resemblance to the Sporothrix Beurmanni. PMID- 20310590 TI - Notes on Glaucoma. PMID- 20310591 TI - Carcinoma of the Breast in a Man with Apparently Healed Miliary Tuberculosis. PMID- 20310592 TI - A Chiropractical Joke. PMID- 20310593 TI - Appendicular Obstruction. PMID- 20310594 TI - Imperial Reciprocity. PMID- 20310595 TI - Editorial Notes. PMID- 20310596 TI - Saving the Teeth. PMID- 20310598 TI - The Use of the Bone Graft in Surgery. PMID- 20310597 TI - "Pelvic Inflammation". PMID- 20310599 TI - Bone Wedging-A Method of Eliminating the Introduction of Foreign Materials in Open Operations on Fractures. PMID- 20310600 TI - Early Diagnosis of Tuberculosis. PMID- 20310601 TI - Septic Thrombo-Phlebitis of the Portal Vein, complicating Gangrenous Appendicitis. PMID- 20310602 TI - An Ideal Military Hospital. PMID- 20310603 TI - The Manufacture of Salvarsan in Canada. PMID- 20310604 TI - The Canadian Red Cross. PMID- 20310605 TI - Our Belgian Confreres. PMID- 20310606 TI - The Quebec Medical Board. PMID- 20310607 TI - Editorial Notes. PMID- 20310608 TI - NO. 1 GENERAL HOSPITAL. PMID- 20310609 TI - TO INCREASE BRITISH TRADE. PMID- 20310610 TI - The War: Hospital Experiences in France. PMID- 20310611 TI - The Acute Abdomen: A Clinical Study. PMID- 20310612 TI - The Diagnosis and Treatment of Gastric and Duodenal Ulcers. PMID- 20310613 TI - The Involvement of the Central Nervous System in Symphilis. PMID- 20310614 TI - Pyelitis as a Complication of Pregnancy and the Puerperium. PMID- 20310615 TI - The Early Diagnosis of Gastric Carcinoma: A Comparison of Clinical and Roentgen Methods. PMID- 20310616 TI - The Boas-Oppler Bacillus (lactic acid bacillus), and the Diagnostic Importance of its Presence in the Gastric Contents. PMID- 20310617 TI - Artificial Pneumothorax in the Treatment of Tuberculosis. PMID- 20310618 TI - A Case of Extramedullary Angioma of the Spinal Cord. PMID- 20310619 TI - Venereal Prophylaxis among the Troops. PMID- 20310620 TI - Compulsory Inoculation. PMID- 20310621 TI - The Ambulance Construction Commission. PMID- 20310622 TI - Meningitis in Camps. PMID- 20310623 TI - Editorial Notes. PMID- 20310624 TI - The Biological and other Blood Tests in the Law Courts. PMID- 20310625 TI - Boulogne in War Time. PMID- 20310626 TI - Artificial Pneumothorax in the Treatment of Phthisis: Part I. PMID- 20310627 TI - Vaccines in the Treatment of Bacterial Diseases of the Lungs Complicating Pulmonary Tuberculosis and Their Preparation. PMID- 20310628 TI - Blood Transfusion in Infants and Young Children. PMID- 20310629 TI - Notes on Some Dislocations. PMID- 20310631 TI - Civil Practice and Military Needs. PMID- 20310630 TI - The Curative Value of Tetanus Antitoxin. PMID- 20310632 TI - Clean Milk. PMID- 20310633 TI - Editorial Notes. PMID- 20310634 TI - Professor Wesley Mills: Born, February 22nd, 1847 Dead, February 13th, 1915. PMID- 20310635 TI - War Notes, II. PMID- 20310636 TI - Artificial Pneumothorax in the Treatment of Phthisis: Part II. PMID- 20310637 TI - Uterine Haemorrhage at and after the Menopause. PMID- 20310638 TI - Some Sequelae of Antityphoid Inoculation. PMID- 20310639 TI - Juvenile Delinquency. PMID- 20310641 TI - The Postponement of the Meeting. PMID- 20310640 TI - Foetus in Foetu. PMID- 20310642 TI - The Association's Affairs. PMID- 20310643 TI - The New British Pharmacopeia. PMID- 20310644 TI - Editorial Notes. PMID- 20310645 TI - Feeble-Mindedness and the State. PMID- 20310646 TI - Presidential Address. PMID- 20310647 TI - Prophylactic Inoculation Against Typhoid Fever in the Fourth Militia Divisional Area of Canada. PMID- 20310648 TI - Artificial Pneumothorax in the Treatment of Phthisis. PMID- 20310649 TI - On the Occurrence of Fluid Exudate in Cases of Lobar Pneumonia. PMID- 20310650 TI - A Case of Multiple Facetted Calculi of the Penile Urethra. PMID- 20310651 TI - The Meeting of the Association of American Physicians. PMID- 20310652 TI - The Use of Asphyxiating Gases. PMID- 20310653 TI - Editorial Notes. PMID- 20310654 TI - Tuberculosis in Minnesota. PMID- 20310655 TI - A Letter from No. 1 General Hospital, C.E.F. PMID- 20310656 TI - On the Relation of Anatomical Structure and of Antagonism between Organs to Disease. PMID- 20310657 TI - Parenteral Digestion and Immunity. PMID- 20310658 TI - The Phenomena of Anaphylaxis and Allergy and their Relationship to Immunity. PMID- 20310659 TI - Prophylactic Use of Bacterial Vaccines. PMID- 20310660 TI - The Therapeutic Employment of Vaccines. PMID- 20310661 TI - Fat Metabolism and its Relation to Acidosis. PMID- 20310662 TI - A CASE OF HAEMORRHAGIC CHICKEN-POX. PMID- 20310663 TI - Patent Medicines and Infectious Diseases. PMID- 20310664 TI - Tuberculosis in Children. PMID- 20310665 TI - Determination of Sex. PMID- 20310666 TI - Editorial Notes. PMID- 20310667 TI - The Pharmacology of Animal Extracts. PMID- 20310668 TI - Organo-therapy in Obstetrical and Gynaecological Practice. PMID- 20310669 TI - Animal Extracts in Surgery. PMID- 20310670 TI - Animal Extracts in Rhinology and Laryngology. PMID- 20310671 TI - Animal Extracts in Ophthalmology. PMID- 20310673 TI - Experimental gastro-enterostomy. PMID- 20310672 TI - Syphilis of the Heart and Aorta. PMID- 20310674 TI - A resume of the Evening Clinic for Diagnosis of Diseases of the Chest at the Boston City Hospital. PMID- 20310676 TI - Gastric Ulcer and Gastric Cancer. PMID- 20310675 TI - Series of Unusual Surgical Conditions. PMID- 20310678 TI - Editorial notes. PMID- 20310677 TI - A Question of priority. PMID- 20310679 TI - Res Judicatae: War Wounds-the Prevalence of Infection-Treatment. PMID- 20310680 TI - Correspondence from the Seat of War. PMID- 20310681 TI - Address on Surgery. PMID- 20310682 TI - Appendicitis: An Appreciation of the Ochsner Method. PMID- 20310683 TI - Bacteriology of Hodgkin's Disease: A Review. PMID- 20310684 TI - The Practical Value of a Knowledge of the Sympathetic and Autonomic Nervous System. PMID- 20310685 TI - Tissue Respiration in the Light of Recent Research. PMID- 20310686 TI - Foreign Body in OEsophagus. PMID- 20310688 TI - Twilight Sleep: the Dammerschlaf of the Germans. PMID- 20310687 TI - An Unusual Case of a Needle Lodged in the Duodenum. PMID- 20310689 TI - The Descriptive Catalogue of the Medical Museum of McGill University. PMID- 20310690 TI - On the Amount of Butter Fat in Ice Cream. PMID- 20310691 TI - Editorial notes. PMID- 20310692 TI - Correspondence: Butter Fat in Ice Cream. PMID- 20310693 TI - Canadian Literature: Original Contributions. PMID- 20310694 TI - Disabilities, including Injuries, caused by Bullets, Shrapnel, High Explosives, etc., as illustrated by cases examined before a medical board at Canadian Headquarters, Shorncliffe, England. PMID- 20310696 TI - A case of Large Celled Splenomegaly : (Gaucher type). PMID- 20310695 TI - Non-materialism in Medicine. PMID- 20310697 TI - The Subcutaneous Administration of Fluid in Acute and Subacute Conditions in Infancy. PMID- 20310698 TI - The Methods of Dealing with Tuberculosis in the Public Schools of Toronto. PMID- 20310699 TI - Cholaemic Haemorrhage. PMID- 20310700 TI - Typhoid Cholelithiasis and Cholecystitis. PMID- 20310702 TI - Egyptian Ophthalmia. PMID- 20310701 TI - Paul Ehrlich. PMID- 20310703 TI - Editorial Notes. PMID- 20310704 TI - Correspondence from the seat of war: No. 3 Canadian General Hospital, McGill. PMID- 20310705 TI - Correspondence: The late Professor A. W. H. Lindsay, of Halifax. PMID- 20310706 TI - Canadian Literature: Original Contributions. PMID- 20310707 TI - The Prevention and Control of Cancer. PMID- 20310708 TI - The Medical Schools. PMID- 20310709 TI - Editorial Notes. PMID- 20310710 TI - Res Judicandae: Work for the Aged Physicians. PMID- 20310711 TI - Correspondence From the Seat of War. PMID- 20310712 TI - Canadian Literature: Original Contributions. PMID- 20310713 TI - Medical Ideals in the Ancient World: The Opening Lecture of the 84th Session of the Medical Faculty of McGill University. PMID- 20310714 TI - Remarks on the Character and Treatment of Wounds in War. PMID- 20310715 TI - Delivery by Hysterotomy-Five Instances. PMID- 20310716 TI - Dyspnoea in Cardio-renal Disease. PMID- 20310717 TI - Acute OEdema of the Lungs. PMID- 20310719 TI - The Medical Profession and the War-The Cancer Problem. PMID- 20310718 TI - A Case of Severe Pharyngitis in Association with Erysipelas. PMID- 20310720 TI - Aids in the Diagnosis of Surgical Conditions of the Stomach with Especial Reference to the Characteristic x-ray appearance of the Syphilitic Hour-Glass in Contrast to those of Simple Ulcer and Cancer. PMID- 20310721 TI - Anti-typhoid Inoculation. PMID- 20310722 TI - Influenza Meningitis with Report of Two Cases. PMID- 20310723 TI - Clolelithiasis and Chronic Valvular Disease. PMID- 20310724 TI - Transfusion. PMID- 20310725 TI - The Ontario Commission. PMID- 20310726 TI - Editorial Notes. PMID- 20310727 TI - The Medical Profession of Ontario versus The Irregular Practitioner. PMID- 20310729 TI - Canadian Literature: Original Contributions. PMID- 20310728 TI - Memorandum to Regimental Medical Officers, issued by Lieutenant-Colonel J. T. Fotheringham, A.D.M.S., Second Canadian Division. PMID- 20310730 TI - Presidential Address. PMID- 20310731 TI - Dermatology and the General Practitioner. PMID- 20310732 TI - Treatment of Squint. PMID- 20310733 TI - Static Joint Disease. PMID- 20310734 TI - Notes on Cortical Localization. PMID- 20310735 TI - Stab Wound of Liver. PMID- 20310736 TI - The "Carrier" Problem. PMID- 20310737 TI - Dr. Edward Livingstone Trudeau: A Tribute. PMID- 20310738 TI - Soldiers' Wives and Free Medical Treatment. PMID- 20310739 TI - Editorial Notes. PMID- 20310741 TI - The Origin of the Naso-antral Polyp. PMID- 20310740 TI - Correspondence. PMID- 20310742 TI - Correspondence From the Seat of War. PMID- 20310743 TI - Canadian Literature: Original Contributions. PMID- 20310744 TI - Eclampsia. PMID- 20310745 TI - The Psycho-Neuroses: Observations Based Upon One Hundred Strongly Marked Cases Seen in Orthopedic Practice. PMID- 20310746 TI - Cystic Hygroma in an Infant. PMID- 20310748 TI - Canadian Military Hospitals. PMID- 20310747 TI - A Well-Deserved Honour. PMID- 20310749 TI - Editorial Notes. PMID- 20310750 TI - Correspondence from the Seat of War. PMID- 20310751 TI - Ontario Medical Commission: Statement by the Authorities of the University of Toronto. PMID- 20310752 TI - Canadian Literature: Original Contributions. PMID- 20310753 TI - Twilight Sleep. PMID- 20310754 TI - Acupuncture the best means of Vaccination against Smallpox. PMID- 20310755 TI - Eyestrain. PMID- 20310756 TI - Science and Medicine. PMID- 20310758 TI - Pellagra. PMID- 20310757 TI - The Method of Examination and Results in Sight, Hearing and Colour Vision for one year on the Grand Trunk Railway System. PMID- 20310759 TI - Ruptured Tubal Pregnancy. PMID- 20310760 TI - Unusual Case of Eclampsia. PMID- 20310761 TI - The Halifax Military Commission. PMID- 20310762 TI - The problem of the Mental Defectives. PMID- 20310763 TI - Department of Public Health. PMID- 20310764 TI - Editorial Notes. PMID- 20310765 TI - Canadian Literature: Original Contributions. PMID- 20310766 TI - Ontario Medical Commission. PMID- 20310767 TI - Effects of Wet and Cold: Trench Feet. PMID- 20310768 TI - Number One Canadian General Hospital as a part of the Canadian Medical Organization in France. PMID- 20310769 TI - Incidents in the Life of a Physician. PMID- 20310770 TI - A Panoramic Sketch. PMID- 20310771 TI - The Provincial Health Act: Its Merits and Defects. PMID- 20310772 TI - Paralysis from Fright. PMID- 20310773 TI - Cancer of the Stomach and Pellagra in the same Patient. PMID- 20310775 TI - Orthopaedic After-treatment of Canadian Wounded. PMID- 20310774 TI - Sarcoma of the Intestines in a Child Seven Years of Age. PMID- 20310776 TI - Trench Feet. PMID- 20310777 TI - Captain F. A. C. Scrimger. PMID- 20310778 TI - The Military Hospitals Commission. PMID- 20310779 TI - Special Summer Courses to Provide Early Graduation for Medical Students. PMID- 20310781 TI - Ontario Medical Association Meeting. PMID- 20310780 TI - Editorial Notes. PMID- 20310783 TI - Report of the Royal Commission on Venereal Disease. PMID- 20310782 TI - Trench Nephritis. PMID- 20310784 TI - The Factor of Poverty in Sanitation. PMID- 20310785 TI - Correspondence from the Seat of War. PMID- 20310786 TI - Hospital Diets and their Relation to the Treatment of Certain Diseases. PMID- 20310787 TI - The Medical Beliefs and Superstitions of the Keltic Race. PMID- 20310788 TI - Prostatic Hypertrophy and Treatment by Suprapubic Prostatectomy. PMID- 20310789 TI - The Results of a Year's Work in the Treatment of Acute Appendicitis. PMID- 20310791 TI - Double Facial Paralysis. PMID- 20310790 TI - Amoebic Dysentery. Amoebic Abscess of the Liver. PMID- 20310792 TI - Hospital Dietetics. PMID- 20310793 TI - Canadian Medical Association. PMID- 20310794 TI - Social Service and Hospitals. PMID- 20310795 TI - Canadian Red Cross Society. PMID- 20310796 TI - Editorial Notes. PMID- 20310798 TI - Canadian Literature: Original Contributions. PMID- 20310797 TI - The Relation of "Sanitation" to Death and Disease. PMID- 20310799 TI - Ontario Medical Association: Presidential address. PMID- 20310800 TI - Notes from the McGill General Hospital in France. PMID- 20310801 TI - Acute Mammary Carcinoma: (Volkmann's Mastitis Carcinimatosa). PMID- 20310802 TI - Suppurative Otitis Media. PMID- 20310803 TI - Dr. Edsall on the Study of the Respiration. PMID- 20310804 TI - The Congress of American Physicians and Surgeons. PMID- 20310805 TI - Editorial Notes. PMID- 20310807 TI - Correspondence from the seat of war. PMID- 20310808 TI - Canadian Literature: Original Contributions. PMID- 20310806 TI - Report from the Laboratory of No. 3 Canadian General Hospital-McGill. PMID- 20310809 TI - Drugs and Medicinal Agents Considered from the Professional, Economic and National Standpoints. PMID- 20310810 TI - The Surgical Treatment of Gastric and Duodenal Ulcer. PMID- 20310811 TI - The Operative Treatment of Simple Fractures. PMID- 20310812 TI - Penetrating Gastric Ulcer with Specimen. PMID- 20310813 TI - The Association. PMID- 20310814 TI - Report of the Special Advisory Committee on Cerebro-Spinal Fever. PMID- 20310815 TI - Soldier's Heart and the Hampstead Hospital. PMID- 20310816 TI - Editorial Notes. PMID- 20310817 TI - Canadian Literature: Original Contributions. PMID- 20310819 TI - Radiology. PMID- 20310818 TI - The Operative Treatment of Pyloric Obstruction in Infants. PMID- 20310820 TI - The Treatment of Diabetes Mellitus. PMID- 20310822 TI - Medical Work at a Base Hospital in France. PMID- 20310821 TI - The Colloidal Gold Test in Cerebro-Spinal Fluids. PMID- 20310823 TI - Meningococcus Meningitis. PMID- 20310824 TI - The Definite Treatment of Pneumonia: With a Report of the Germicidal Power of Quinine and other Cinchona Derivatives upon Pneumococcus Cultures in vitro. PMID- 20310825 TI - The Transthoracic Operation for Chronic Empyema and for Bronchiectasis. PMID- 20310826 TI - Blood Transfusion in Haemorrhage of the Newborn. PMID- 20310827 TI - Pruritis in Oral Sepsis. PMID- 20310828 TI - The Surgical Aspects of the Congress of American Physicians and Surgeons. PMID- 20310829 TI - The Lange Colloidal Gold Test. PMID- 20310830 TI - The Canadian Red Cross Society. PMID- 20310831 TI - Editorial notes. PMID- 20310832 TI - Res Judicatae: Can we keep Tonsils and Adenoids from becoming diseased? PMID- 20310834 TI - An Epidemic of Pneumococcus Infection. PMID- 20310833 TI - Canadian Literature: Original Contributions. PMID- 20310835 TI - A Brief Survey of Some Experiences in the Surgery of the Present War. PMID- 20310837 TI - The Field Ambulance and Its Organization. PMID- 20310836 TI - The Irritable Heart of Soldiers (Soldier's Heart). PMID- 20310839 TI - Colds Explained. PMID- 20310838 TI - Treatment of Diphtheria at the Alexandra Hospital, Montreal. PMID- 20310840 TI - War Surgery. PMID- 20310841 TI - Editorial notes. PMID- 20310842 TI - Retrospect of Literature. PMID- 20310843 TI - Presidential Address delivered before the Canadian Association for the Prevention of Tuberculosis. PMID- 20310844 TI - Presidential Address delivered before the New Brunswick Medical Society. PMID- 20310846 TI - Malignant OEdema. PMID- 20310845 TI - Psychogenetic Conditions. PMID- 20310847 TI - Epidemic Meningitis. PMID- 20310848 TI - Posture as an Aid to Treatment. PMID- 20310849 TI - Syphilis: Its Cause and Treatment. PMID- 20310850 TI - Appendico-vesical Fistula. PMID- 20310851 TI - 1. Bilharzias. PMID- 20310852 TI - 2. Sacrolization of Lumbar Vertebra. PMID- 20310853 TI - 3. Case Presented by Captain Collins, C.A.M.C. PMID- 20310854 TI - 4. Pyloric Ulcer. PMID- 20310855 TI - The Recent Epidemic of Poliomyelitis. PMID- 20310856 TI - The Tuberculous Soldier. PMID- 20310858 TI - The Clayton Convalescent Home. PMID- 20310857 TI - A Permanent Pensions Board. PMID- 20310859 TI - Editorial Notes. PMID- 20310860 TI - Retrospect of Literature: Ulceromembranous Stomatitis and Gingivitis among Troops; Its Cause and Treatment. PMID- 20310861 TI - Considerations in the Diagnosis and Surgical Treatment of Gastric and Duodenal Ulcer. PMID- 20310862 TI - Five Clinical Cases showing Clinical Aspects of Primary and Secondary Syphilis. PMID- 20310863 TI - The Treatment of Soldiers Suffering from Pulmonary Tuberculosis. PMID- 20310864 TI - An Undeserved Reproach. PMID- 20310865 TI - Dr. Cameron on Homologous Twins. PMID- 20310866 TI - Vocational Training. PMID- 20310868 TI - Canadian Literature: Original Contributions. PMID- 20310867 TI - Editorial Notes. PMID- 20310869 TI - Presidential Address delivered before the Alberta Medical Association. PMID- 20310870 TI - Some Observations on Epidemic Cerebro-spinal Meningitis. PMID- 20310871 TI - The Clinical Pathology of the Cerebro-spinal Fluid. PMID- 20310873 TI - The Mode of Origin of Homologous Twin Pregnancy and its Bearing on the Cell Theory. PMID- 20310872 TI - Some Cases of Syphilis of the Eye following Treatment by Salvarsan. PMID- 20310874 TI - Gunshot wounds of the present war. PMID- 20310875 TI - Internal secretions. PMID- 20310876 TI - Appendicitis. PMID- 20310877 TI - Earlier diagnosis of pulmonary tuberculosis. PMID- 20310878 TI - Notes on special work in a field ambulance. PMID- 20310879 TI - A case of shell shock. PMID- 20310880 TI - A foreign body in a tumour of the anterior abdominal wall. PMID- 20310881 TI - Pyosalpinx complicating ectopic gestation. PMID- 20310882 TI - The Association. PMID- 20310883 TI - The Canadian Medical Services. PMID- 20310884 TI - Medical Research and the War. PMID- 20310885 TI - Infantile Paralysis. PMID- 20310886 TI - Editorial notes. PMID- 20310887 TI - Canadian Literature: Original Contributions. PMID- 20310888 TI - Pyloric Stenosis in Infants. PMID- 20310889 TI - Tuberculosis often of Secondary Importance to other Pathological Conditions. PMID- 20310890 TI - Blood Transfusion. PMID- 20310891 TI - The Treatment and Management of Congenital Syphilis. PMID- 20310892 TI - The Modern Treatment of Syphilis. PMID- 20310893 TI - Anti-tuberculosis Work in a small city: "The visiting nurse". PMID- 20310894 TI - Fallacies in the Localization of Foreign Bodies by the x-Ray. PMID- 20310895 TI - On the Segregation Policy. PMID- 20310896 TI - Medical Inspection of Schools. PMID- 20310897 TI - Meeting of the Ontario Medical Association. PMID- 20310898 TI - Editorial Notes. PMID- 20310899 TI - The Montreal Meeting. PMID- 20310900 TI - Correspondence. PMID- 20310901 TI - Canadian Literature: Original Contributions. PMID- 20310902 TI - Some Clinical Aspects of Acute Anterior Poliomyelitis. PMID- 20310903 TI - Poliomyelitis as seen by the Surgeon. PMID- 20310904 TI - The Advantages of Early Sanatorium Treatment. PMID- 20310905 TI - Dislocations of the Spine. PMID- 20310906 TI - Hay Fever. PMID- 20310907 TI - Diabetes Mellitus in a Child of Three. PMID- 20310909 TI - The Special Board of Enquiry. PMID- 20310908 TI - Infantile Eczema and Status Lymphaticus. PMID- 20310911 TI - The Care of the Soldier's Teeth. PMID- 20310910 TI - An Appeal to the Profession. PMID- 20310912 TI - Paratyphoid. PMID- 20310913 TI - Editorial Notes. PMID- 20310914 TI - Report of the Board of Enquiry. PMID- 20310915 TI - The Montreal Meeting. PMID- 20310916 TI - Paratyphoid in the Army at the Dardanelles. PMID- 20310917 TI - Functional Reeducation and Vocational Training of Soldiers disabled in War. PMID- 20310918 TI - Sphagnum Moss for Use as a Surgical Dressing; Its Collection, Preparation and other Details. PMID- 20310919 TI - End results of the various Disabilities of the Returned Soldier. PMID- 20310920 TI - The Treatment of Syphilis: Its effect upon the Wassermann Test using high Dilutions of Serum. A priliminary note. PMID- 20310921 TI - The Medical Treatment of Obstetric Cases. PMID- 20310922 TI - A Satisfactory Method of obtaining Blood for Diagnostic purposes in Infancy, with a Preliminary Report on Longitudinal Sinus Transfusion. PMID- 20310923 TI - Newer Views on Ventilation. PMID- 20310924 TI - The Ability of Mothers to Nurse their Infants. PMID- 20310926 TI - The Marlow Medical Report. PMID- 20310925 TI - Returned Invalid Soldiers. PMID- 20310927 TI - "The R. P. Campbell Memorial Fund". PMID- 20310928 TI - The Antitoxin Laboratory of the University of Toronto. PMID- 20310929 TI - Editorial Notes. PMID- 20310930 TI - The Montreal Meeting. PMID- 20310931 TI - Canadian Literature: Original Contributions. PMID- 20310932 TI - War Nephritis. PMID- 20310933 TI - Abdominal Wounds as seen at a Casualty Clearing Station. PMID- 20310934 TI - Notes on War Surgery. PMID- 20310935 TI - Subacute Combined Sclerosis. PMID- 20310936 TI - Duodenal Ulcers in Infancy. PMID- 20310937 TI - On Oleomargarine. PMID- 20310938 TI - Flavine and Brilliant Green. PMID- 20310939 TI - The "American Review of Tuberculosis". PMID- 20310940 TI - Editorial Notes. PMID- 20310941 TI - Returned Soldiers and the Medical Profession. PMID- 20310942 TI - Canadian Literature: Original Contributions. PMID- 20310943 TI - Remote Symptoms from Lesions of the Prostate and Deep Urethra. PMID- 20310944 TI - Diagnosis of Tumours in the Upper Zone of the Abdomen. PMID- 20310945 TI - The Acute Abdomen. PMID- 20310946 TI - Nitrous Oxide-Oxygen Analgesia and Anaesthesia in Obstetrics. PMID- 20310947 TI - An Analysis of Three Thousand Cases of Obstetrics. PMID- 20310948 TI - Heliotherapy in Abdominal Tuberculosis. PMID- 20310950 TI - Transfusion in Ruptured Ectopic Pregnancy. PMID- 20310949 TI - A Short Discussion of some Phases of Gastric and Duodenal Ulcers with report of cases. PMID- 20310952 TI - Nitrous Oxide-Oxygen Analgesia in Obstetrics. PMID- 20310951 TI - Heliotherapy. PMID- 20310953 TI - Editorial Notes. PMID- 20310954 TI - Canadian Literature: Original Contributions. PMID- 20310955 TI - Diabetes Associated with Haemochromatosis. PMID- 20310956 TI - The Modern Laboratory Investigation of a Nephritic. PMID- 20310957 TI - Fractures of the Skull from a Neurological Standpoint. PMID- 20310958 TI - Finch and Baines-A Seventeenth Century Friendship. PMID- 20310959 TI - The Activities of a Provincial Association. PMID- 20310961 TI - Editorial notes. PMID- 20310960 TI - A Federal Department of Public Health. PMID- 20310962 TI - Canadian Literature: Original Contributions. PMID- 20310963 TI - Presidential Address delivered before the Canadian Medical Association. PMID- 20310964 TI - Address in Medicine. Slight variations from normal structure and function, and their clinical significance. PMID- 20310966 TI - Pyelitis. PMID- 20310965 TI - The Corpus Callosum-A morphological and clinical study. PMID- 20310967 TI - Suggestions for a further Classification of cases of so-called Shell Shock. PMID- 20310968 TI - Fragilitas Ossium, with report of a case. PMID- 20310969 TI - Traumatic extra-peritoneal Rupture of the Bladder with Fracture of the Pelvis. PMID- 20310970 TI - The President's Address. PMID- 20310971 TI - The Address in Medicine. PMID- 20310972 TI - A Canadian Cavendish Lecturer. PMID- 20310973 TI - Sir William C. Macdonald. PMID- 20310974 TI - Editorial Notes. PMID- 20310975 TI - Canadian Literature: Original Contributions. PMID- 20310976 TI - Address in Surgery. Past and Present. PMID- 20310977 TI - Public Address in State Medicine. The modern conception of Public Health Administration and its National Importance. PMID- 20310978 TI - A Study of certain Psychogenetic conditions among Soldiers. PMID- 20310979 TI - Discussion of certain Borderline Problems. PMID- 20310980 TI - The Montreal Meeting. PMID- 20310981 TI - The Address in Surgery. PMID- 20310982 TI - Modern conception of Public Health Administration. PMID- 20310983 TI - University Hospital Units. PMID- 20310984 TI - The Venereal Disease Problem. PMID- 20310985 TI - Editorial Notes. PMID- 20310987 TI - Canadian Literature: Original Contributions. PMID- 20310986 TI - Letter from Lieutenant-Colonel G. E. Armstrong, C.A.M.C. PMID- 20310988 TI - Anaesthesia from commercial ether-administration and what it is due to. PMID- 20310989 TI - Shrapnel Balls. Their x-ray characteristics, compared with bullets and other foreign bodies. PMID- 20310990 TI - The radical cure of inguinal hernia. PMID- 20310991 TI - An unusual form of subconjunctival cyst. PMID- 20310992 TI - Complications of mastoiditis. PMID- 20310993 TI - Medical education in Japan. PMID- 20310995 TI - Ozena among the various races of the earth. PMID- 20310994 TI - Helping to solve a prairie problem: How the People of the Western Provinces are endeavouring to Provide Hospital Accommodation for their Rural Sick. PMID- 20310996 TI - Bacteriuria in some chronic diseases with special reference to intestinal stasis. PMID- 20310997 TI - A report of the spring-balance muscle tests as devised by Lovett. PMID- 20310998 TI - Case of Vaquez's disease. PMID- 20310999 TI - Fracture in utero; pregnancy in bicornuate uterus; typhoid fever. PMID- 20311000 TI - The organization of provincial associations. PMID- 20311001 TI - Doctor Cotton's paper on the causation of ether anaeathesia. PMID- 20311002 TI - Editorial notes. PMID- 20311003 TI - Correspondence. PMID- 20311004 TI - Candian Literature: Original Contributions. PMID- 20311005 TI - From the Vague to the Concrete in Science and Medicine. PMID- 20311006 TI - Sanitary Records of Houses. PMID- 20311008 TI - Hysteria in the Male. PMID- 20311007 TI - The Care and Treatment of Mental Defectives. PMID- 20311009 TI - A Short Series of Cases of Carcinoma of the Cervix Uteri. PMID- 20311010 TI - The Deficiency Diseases of Infancy and Childhood. PMID- 20311011 TI - Case Reports of Kidney Specimens presented before the Montreal Medico-Chirurgical Society, March 30th, 1917. PMID- 20311012 TI - An Antitoxin for Gas Gangrene. PMID- 20311013 TI - Editorial Notes. PMID- 20311015 TI - Symposium on Suppurative Conditions in the Lower Respiratory Tract: Surgical Aspects. PMID- 20311014 TI - Correspondence. PMID- 20311016 TI - Symposium on Suppurative Conditions in the Lower Respiratory Tract: Roentgenological Aspects. PMID- 20311017 TI - The Canadian Medical Profession and the War. PMID- 20311018 TI - Revere Osler. PMID- 20311019 TI - Editorial Notes. PMID- 20311020 TI - Res Judicandae: Arthropod Parasites Suggested as a Factor in the AEtiology of Soldier's Heart and Allied War Diseases. PMID- 20311021 TI - Canadian Literature: Original Contributions. PMID- 20311022 TI - Presidential Address. Academy of Medicine, Toronto. PMID- 20311023 TI - The Technique of Nerve Suture. PMID- 20311024 TI - Symposium on Suppurative Conditions in the Lower Respiratory Tract: Medical Aspects. PMID- 20311025 TI - The treatment of nerve, muscle, and joint injuries in soldiers by physical means. PMID- 20311026 TI - The use of Epsom salts, historically considered. PMID- 20311027 TI - On the modern methods of the treatment of fractures. PMID- 20311028 TI - Some common foot conditions and their treatment. PMID- 20311029 TI - Cyclic vomiting in relation to acid intoxication. PMID- 20311030 TI - Foci of infection in the tonsils. PMID- 20311031 TI - Notes on the treatment of bacillary dysentery. PMID- 20311033 TI - The physical reeducation of disabled soldiers. PMID- 20311032 TI - Primary asthma in a pregnant multipara. PMID- 20311034 TI - Vocational reeducation of returned soldiers. PMID- 20311035 TI - German drugs and medicinal agents and the Canadian market. PMID- 20311037 TI - Editorial notes. PMID- 20311036 TI - The Connaught Laboratories. PMID- 20311038 TI - Correspondence. Letter from the Synthetic Drug Company, Toronto. PMID- 20311039 TI - Canadian Literature. PMID- 20311040 TI - Vocational training in the treatment of pulmonary tuberculosis. PMID- 20311041 TI - The effects of gassing as seen at a Casualty Clearing Station. PMID- 20311042 TI - On the modification in the strength of the Bordet-Wassermann test during the treatment of syphilis. PMID- 20311043 TI - Empyema cavities. PMID- 20311044 TI - Home treatment of tuberculosis. PMID- 20311045 TI - Purpuric Measles. PMID- 20311046 TI - The need of an army medical museum as part of the Army Medical Service. PMID- 20311047 TI - The great war exhibit at the Royal College of Surgeons. PMID- 20311049 TI - Editorial notes. PMID- 20311048 TI - Appointment of A.D.M.S. Invalids. PMID- 20311050 TI - The Halifar Disaster. PMID- 20311051 TI - The medical week in Hamilton. PMID- 20311052 TI - The War: Extracts from letter written by Captain G. Shanks, No. 1 British General Hospital in Mesopotamia. PMID- 20311054 TI - Canadian Literature: Original Contributions. PMID- 20311053 TI - Diagnosis of renal tuberculosis, from the Department of Urology, Royal Victoria Hospital, Montreal. PMID- 20311055 TI - Suprapubic prostatectomy. PMID- 20311056 TI - The surgical treatment of pernicious anaemia. PMID- 20311057 TI - Minor infections and quarantine: Presidential address was given by Dr. Lincoln in 1917. PMID- 20311058 TI - How a medical health officer can become a cooperative social force in rural districts. PMID- 20311059 TI - Development of haemorrhagic disease following injury to the liver. PMID- 20311060 TI - Anthrax of face. PMID- 20311061 TI - Dr. Theodore C. Janeway. PMID- 20311062 TI - Reporting of accidents from local anaesthetics. PMID- 20311063 TI - War nephritis. PMID- 20311064 TI - New Year's Honours to Sir Andrew Macphail and other Canadians. PMID- 20311065 TI - Editorial notes. PMID- 20311066 TI - Medical week in Hamilton. PMID- 20311068 TI - Canadian literature: Original Contributions. PMID- 20311067 TI - Correspondence: Reporting accidents from local anaesthetics. PMID- 20311069 TI - Anthrax in man with a report of two cases. PMID- 20311070 TI - The danger of the external use of wood alcohol. PMID- 20311071 TI - A brief consideration of the static labyrinth and ear tests for aviators. PMID- 20311072 TI - A clinical report on one hundred and thirty-one cases treated by artificial pneumothorax. PMID- 20311074 TI - Duct papilloma and duct carcinoma of the breast. PMID- 20311073 TI - The after-history of war nephritis War nephritics invalided to England. PMID- 20311075 TI - Rupture of intestines by blows upon abdomen. PMID- 20311076 TI - Traumatic rupture of the jejunum: Operation-Recovery. PMID- 20311077 TI - Report of six cases of tonsillectomy in diphtheria carriers. PMID- 20311078 TI - Repair of nose by transferred flap operation with included bonegraft. PMID- 20311079 TI - Lieutenant-Colonel John McCrae, B.A., M.B., M.R.C.P. PMID- 20311080 TI - Editorial notes. PMID- 20311082 TI - Montreal Medico-Chirurgical Society. PMID- 20311081 TI - Canadian Literature: Original Contributions. PMID- 20311084 TI - Notes from a Canadian Hospital in the Near East. PMID- 20311083 TI - Modern conceptions of certain immunity reactions and their practical bearing. PMID- 20311085 TI - An experience through the Halifax disaster. PMID- 20311086 TI - Analysis of clinical types of puerperal fever with special reference to prognosis and treatment. PMID- 20311087 TI - The essentials of success in prostatic surgery. PMID- 20311088 TI - The establishment of a federal bureau of health. PMID- 20311090 TI - Mercury poisoning with anaphylactic phenomena and fatal issue fifty-two days later. PMID- 20311091 TI - A case of rheumatic fever with purpura, oedema of the glottis, etc. PMID- 20311089 TI - Two cases of sinus thrombosis and jugular resection. PMID- 20311092 TI - Legislation for protection against venereal disease. PMID- 20311093 TI - Editorial Notes. PMID- 20311094 TI - Canadian Literature: Original Contributions. PMID- 20311095 TI - Pancreatic cysts. PMID- 20311097 TI - Note on the handling and after history of heart affections in soldiers. PMID- 20311096 TI - Cholecystectomy-a useful technique. PMID- 20311098 TI - The diagnosis of disseminated sclerosis. PMID- 20311099 TI - Tuberculin, its nature and action. PMID- 20311100 TI - The cutaneous manifestations of syphilis. PMID- 20311101 TI - The teaching of hygiene. PMID- 20311103 TI - The invalided soldiers' commission and the new department of soldiers reestablishment. PMID- 20311102 TI - Ruptured ectopic-blood transfusion and pulmonary embolism. PMID- 20311104 TI - Editorial Notes. PMID- 20311105 TI - Canadian Literature: Original Contributions. PMID- 20311106 TI - Montreal Medico-Chirurgical Society. PMID- 20311107 TI - Presidential Address delivered before the Ontario Medical Association: Medicine and Democracy. PMID- 20311108 TI - The determination of basal metabolism by the "Respiratory-valve and spirometer method" of indirect calorimetry, with an observation on a case of polycythemia with splenomegaly. PMID- 20311109 TI - Protein milk-its composition, preparation and application in the treatment of digestive disturbances. PMID- 20311110 TI - Malaria in the army. PMID- 20311111 TI - Pulmonary Abscesses. PMID- 20311112 TI - Two cases of dermoid tumours complicating pregnancy, with operation. PMID- 20311113 TI - The origin, organization and scope of the Canadian National Committee for Mental Hygiene. PMID- 20311115 TI - Medicine and Democracy. PMID- 20311114 TI - Personnel of Committee. PMID- 20311117 TI - Canadian National Committee for Mental Hygiene. PMID- 20311116 TI - Association of American physicians. PMID- 20311118 TI - The admission of women to the study of medicine and allied subjects at McGill University. PMID- 20311119 TI - The report of the commission upon medical education in Ontario. PMID- 20311120 TI - Social service department at McGill. PMID- 20311121 TI - Editorial notes. PMID- 20311122 TI - Special announcement from McGill Graduates' Society re department of social service. PMID- 20311123 TI - Canadian Literature: Original Contributions. PMID- 20311124 TI - No. 1 Canadian General Hospital Clinical Society. PMID- 20311125 TI - Address in medicine. On the Significance of "Heart Murmurs" that may be found on Examination of Candidates for Military Service. PMID- 20311126 TI - Duodeno-jejunostomy, its Indications and Technique. PMID- 20311127 TI - The Diagnosis of Inflammations of the Uveal Tract of Systemic Origin. PMID- 20311128 TI - The Disease Ozaena. PMID- 20311129 TI - Vesical Symptoms in Renal Disease. A Preliminary Report from the Department of Urology Royal Victoria Hospital, Montreal. PMID- 20311130 TI - Abdominal Surgery as a Factor in the Treatment of Pulmonary Tuberculosis. PMID- 20311131 TI - Report of the Special Clinic for the Treatment of Syphilis, Toronto General Hospital. PMID- 20311132 TI - Treatment of Syphilis. Report of Special Clinic for Syphilis, Toronto General Hospital. PMID- 20311133 TI - The Mental Hygiene Movement. PMID- 20311134 TI - Some Notes on the Formation of the Canadian National Committee for Mental Hygiene. PMID- 20311135 TI - The new Director-General of Medical Services to the British forces in France. PMID- 20311137 TI - Municipal Hospitals. PMID- 20311136 TI - The Re-education of the Returned Doctor. PMID- 20311138 TI - Editorial Notes. PMID- 20311139 TI - Resolutions. PMID- 20311140 TI - Psychogenetic Conditions in Soldiers, their AEtiology, Treatment and final Disposal. PMID- 20311141 TI - Chirurgico - Orthopaedic Observations and the Moral Treatment of the Wounded Man. PMID- 20311142 TI - The Surgery of Nerve Injury. PMID- 20311143 TI - On the Role of Physiotherapy in the Treatment of the Returned Soldier. PMID- 20311144 TI - Industrial Rehabilitation. PMID- 20311145 TI - The present Position of Vaccine Therapy. PMID- 20311146 TI - Some Observations in Respect to Public Health. PMID- 20311147 TI - Blindness of the Newborn-A preventable Disease. PMID- 20311148 TI - A Question of Diagnosis. PMID- 20311149 TI - The Hospital Ship Llandovery Castle. PMID- 20311150 TI - The Air Force and the Medical Service. PMID- 20311151 TI - Editorial Notes. PMID- 20311152 TI - THE ASSOCIATION. PMID- 20311153 TI - Report of the Ontario Medical Council in Relation to the Ontario Temperance Act. PMID- 20311154 TI - Appreciation of Sir John Rickman Godlee's Life of Lord Lister. PMID- 20311156 TI - Canadian Literature: Original Contributions. PMID- 20311155 TI - No. 1 Canadian General Hospital Clinical Society. PMID- 20311157 TI - Combined Inquiry into the Presence of Diphtheria and Diphtheroid Bacilli in Open Wounds. PMID- 20311158 TI - The Cancer Problem. PMID- 20311159 TI - The Sociologic and Economic Aspects of Tuberculosis. PMID- 20311160 TI - The Returned Soldier. PMID- 20311162 TI - Cerebro-Spinal Syphilis. PMID- 20311161 TI - The Treatment of Infected Wounds with Dichloramine-T with special Reference to its Advantages over the Carrol-Dakin Method. PMID- 20311163 TI - Synopsis of the Venereal Diseases Prevention Act. PMID- 20311164 TI - The Nursing Crisis. PMID- 20311165 TI - Dr. Emmanuel Persillier Lachapelle. PMID- 20311166 TI - MEDICAL ATTENDANCE ON DISCHARGED SOLDIERS. PMID- 20311167 TI - Editorial Notes. PMID- 20311168 TI - No. 1 Canadian General Hospital Clinical Society. PMID- 20311169 TI - Physiology of the Intracranial Circulation. PMID- 20311170 TI - Intracranial Pressure. PMID- 20311171 TI - The Surgical Relief of Increased Intracranial Pressure. PMID- 20311172 TI - Acute Endo-Carditis in Pregnancy. PMID- 20311173 TI - The Training of the Surgeon. PMID- 20311174 TI - Botulism. PMID- 20311175 TI - The After-Effects of Wounds of the Chest and their Treatment. PMID- 20311177 TI - The Need for Conscription of Canadian Doctors. PMID- 20311176 TI - Medical Inspection of School Children. PMID- 20311178 TI - Terminal Disinfection. PMID- 20311179 TI - Why Federal Legislation is Necessary in order that Venereal Diseases may be effectively dealt with in Canada. PMID- 20311180 TI - Advantages of the Early Diagnosis and Treatment of Syphilis. PMID- 20311182 TI - The Present Epidemic. PMID- 20311181 TI - The Prevention of War Neuroses. PMID- 20311183 TI - The Treatment of Wounds. PMID- 20311184 TI - Letter from British Medical Association, E. Melbourne, Australia. PMID- 20311185 TI - Letter from Lieutenant-Colonel. PMID- 20311186 TI - The Alberta Medical Association. PMID- 20311187 TI - Treatment of Four Hundred and Twenty Infected Wounds under Battle Conditions arriving on the Average of Fifty-Eight and one-third Hours after Injury, without previous Surgical Treatment. PMID- 20311188 TI - Meckel's Diverticulum-Report of Cases causing Intestinal Obstruction. PMID- 20311189 TI - A Study of Four Hundred and Fifty Cases of Wounds of the Chest, with special Reference to a new Method of Treatment for Infected Haemothorax. PMID- 20311190 TI - Mouth Infection as a Source of Systemic Disease. PMID- 20311191 TI - Presidential Address on "Preventive Medicine". PMID- 20311193 TI - Diagrams for showing limitation of movements through joints, as used by the Board of Pensions Commissioners for Canada. PMID- 20311192 TI - A report on the effect of high carbohydrate feeding on the nausea and vomiting of pregnancy. PMID- 20311194 TI - How to provide effective health administration in small (rural) municipalities. PMID- 20311195 TI - Disinfection after communicable disease. PMID- 20311196 TI - The control of influenza in Ontario. PMID- 20311197 TI - The epidemic of influenza. PMID- 20311198 TI - Polya's method of anastomosing the proximal gastric stump with the jejunum. PMID- 20311199 TI - A short note on irregularities of the heart, in association with visceroptosis. PMID- 20311200 TI - Brief case reports from the ear, nose and throat clinics of the Western Hospital, Montreal. PMID- 20311201 TI - NOTES ON TWO CASES OF PECULIAR MEDICAL INTEREST: I. Syphilitic Aortic Insufficiency II. Cerebro-spinal Fever Supervening Upon (?) Erythema Nodosum. PMID- 20311203 TI - A federal department of health. PMID- 20311202 TI - AN UNUSUAL PSYCHONEUROSIS OF WAR: FUNCTIONAL LOSS OF THE SENSE OF SMELL. PMID- 20311204 TI - Montreal Medico-Chirurgical Society. PMID- 20311205 TI - War Activities in Medicine and Surgery: The Address of the President, Academy of Medicine, Toronto. PMID- 20311206 TI - Liquid-Tight Closure and the Treatment of Infected Wounds. PMID- 20311207 TI - The Pensionability of the Disabled Soldier. PMID- 20311208 TI - Medical Services of the Department of Soldiers' Civil Re-Establishment. PMID- 20311209 TI - Preliminary Report on Influenza Epidemic at Bramshott in September-October, 1918. PMID- 20311210 TI - The Work of a Stationery Hospital in the Field. PMID- 20311211 TI - Auto-Serum Treatment of Chorea. PMID- 20311212 TI - Trinitrotoluene Poisoning. PMID- 20311213 TI - Physiology at the Bedside. PMID- 20311214 TI - A National Reserve Organization for Civic Emergencies. PMID- 20311215 TI - Editorial Notes. PMID- 20311216 TI - The Quebec Meeting. PMID- 20311217 TI - Letter from Lieutenant-Colonel W. T. Connell, A.M.C. PMID- 20311218 TI - Some aspects of military ophthalmology. PMID- 20311219 TI - Administration of arsenic in syphilis. PMID- 20311220 TI - Venereal Diseases; their treatment and cure. PMID- 20311221 TI - Artificial pneumothorax in the treatment of pulmonary tuberculosis. PMID- 20311222 TI - The eyesight of the negroes of Africa. PMID- 20311223 TI - Clinical notes on the influenza epidemic occurring in the Quebec garrison. PMID- 20311224 TI - Pleurisy: Experimental and Clinical. PMID- 20311226 TI - Editorial Notes. PMID- 20311225 TI - War-trained specialists for the Board of Pensions. PMID- 20311227 TI - A clinical study of four hundred patients with bronchial asthma. PMID- 20311228 TI - Clinical Observations on the early stages of trench nephritis. PMID- 20311229 TI - The economic effects of disablements. PMID- 20311230 TI - The role of the thymus gland in exophthalmic goitre. PMID- 20311231 TI - Man's place in nature. PMID- 20311232 TI - The return of the army medical officer. PMID- 20311234 TI - Influenza and vaccination. PMID- 20311233 TI - Prostatic massage. PMID- 20311235 TI - Tuberculosis as a causative factor in disordered action of the heart: With Observation upon the Subcutaneous Tuberculin Reaction in Three Hundred Unselected Cases of Disordered Action of the Heart. PMID- 20311236 TI - The Use of x-rays in gastro-intestinal diagnosis. PMID- 20311237 TI - Hospital treatment of summer diarrhoea. PMID- 20311238 TI - Hypernephroma and renal cancers. PMID- 20311239 TI - Congenital bilateral anophthalmos. PMID- 20311240 TI - Pensions to be awarded by the districts. PMID- 20311241 TI - Demobilization of the medical officers. PMID- 20311242 TI - The fraternal societies and tuberculosis. PMID- 20311243 TI - Editorial notes. PMID- 20311244 TI - Letter from the president. PMID- 20311245 TI - The Policy of the Ostrich. PMID- 20311246 TI - Simple Goitre. PMID- 20311247 TI - Venereal Diseases from the Preventive Aspects. PMID- 20311248 TI - Causes and Consequences of Disturbances of Respiratory Rate and Rhythm. PMID- 20311249 TI - A Report of two Cases of Spina Bifida. PMID- 20311250 TI - The Diagnostic Value of the X-Ray Examination in Pulmonary Tuberculosis. PMID- 20311251 TI - Anatomical and Bacteriological Findings in the recent Epidemic Pneumonia. PMID- 20311252 TI - So-Called Trench Mouth and other Manifestations of Vincent's Disease as a spreading Infection in Canada. PMID- 20311253 TI - Official Report on Influenza Epidemic, 1918. PMID- 20311254 TI - Bulletin of the American College of Surgeons on Hospital Standardization. The Importance of Case Records. PMID- 20311255 TI - A Federal Department of Health. PMID- 20311256 TI - House of Commons Medical Committee. PMID- 20311257 TI - The Free Public Hospital Movement. PMID- 20311258 TI - Editorial Notes. PMID- 20311259 TI - The Quebec Meeting. PMID- 20311260 TI - Recent Work on the Chemistry of the Blood and Urine. PMID- 20311261 TI - The Influence of the War on Surgery, Civil and Military. PMID- 20311262 TI - Exophthalmic Goitre. PMID- 20311263 TI - Actinomycotic Infection-with Case Reports. PMID- 20311264 TI - The Recent Epidemic of Pneumonia-Bedside Findings and some Inferences. PMID- 20311265 TI - Terminology of Military Reports. PMID- 20311267 TI - A Further Report upon Diphtheroid Infection of Wounds, with a Note upon the Frequency of Diphtheroid Bacilli in Cases of Urethritis and Prostatitis. PMID- 20311266 TI - Induction of Labour. PMID- 20311269 TI - Post-Graduate Courses for Medical Officers. PMID- 20311268 TI - Proposed Revision of the Constitution and By-Laws of the Association. PMID- 20311270 TI - The Differentiation of Early Tuberculosis and Hyperthyroidism by Means of the Adrenalin Test. PMID- 20311271 TI - Typhoid Spine. PMID- 20311272 TI - A Functional Conception of Pathology as a Basis for the Diagnosis and Treatment of Heart Disease. PMID- 20311273 TI - The Use of a Vaccine in the recent Epidemic of Influenza. PMID- 20311274 TI - Protein Milk Powder. PMID- 20311275 TI - Intestinal Obstruction and its Relation to the General Practitioner. PMID- 20311277 TI - The Report of the Manitoba Welfare Commission. PMID- 20311276 TI - Arthrodesis of the Hip Joint and its Indications. PMID- 20311278 TI - Editorial Notes. PMID- 20311279 TI - Annual Address of the President of the Ontario Medical Association. PMID- 20311280 TI - The Albuminuria of Pregnancy. PMID- 20311281 TI - Focal Infection and Chronic Urticaria. PMID- 20311282 TI - Auricular Flutter and its Treatment. PMID- 20311283 TI - Notes on Diagnosis in Affections of the Urinary Tract. PMID- 20311284 TI - The Application of Rutherford Morison's Technique of Wound Treatment to Civil Surgery. PMID- 20311285 TI - Preliminary Report on the Reconstruction of the Circulation of the Liver, Placenta and Lung in Health and Disease. PMID- 20311286 TI - Radical Cure of Hernia. PMID- 20311287 TI - Living Case: Stricture of the OEsophagus in a Child. PMID- 20311288 TI - Congenital Malformation in Scrotum; Two Testes and Uterus in Right Portion of Scrotum. PMID- 20311289 TI - The Canadian Public Health Association. PMID- 20311290 TI - Post-Graduate Work in Great Britain. PMID- 20311291 TI - Editorial Notes. PMID- 20311292 TI - Presidential Address. PMID- 20311293 TI - The Contribution of the Hospital to the Surgery of To-day: Address in Surgery. PMID- 20311294 TI - Report on Cinematic Amputations Based on a Visit to Putti's Military Clinic in Bologna, Italy. PMID- 20311295 TI - Notes from the Service for Wounds of the Chest. PMID- 20311296 TI - Canadian Doctors and Un-canadian Diseases. PMID- 20311297 TI - Glycosuria in Pregnancy. PMID- 20311298 TI - Vital Statistics-What They Teach. PMID- 20311300 TI - Death Rate Above Age of Forty. PMID- 20311299 TI - The Nervous Conditions Associated with Influenza. PMID- 20311302 TI - The Presidential Address. PMID- 20311301 TI - Congress of American Physicians and Surgeons. PMID- 20311303 TI - The Address in Surgery. PMID- 20311304 TI - Cinematic Amputations. PMID- 20311305 TI - Editorial Notes. PMID- 20311306 TI - Laennec-One Hundred Years After. Address in Medicine. PMID- 20311307 TI - Sanitation in War: Address in Public Health. PMID- 20311308 TI - The Physical Census. PMID- 20311309 TI - A Provincial Ministry of Health. PMID- 20311310 TI - Anti-tuberculosis Leagues in the Districts of Sanitary Inspection. PMID- 20311311 TI - Tuberculosis Hospitals and Dispensaries. PMID- 20311312 TI - Some Danger Signals in Cardiovascular Disease. PMID- 20311313 TI - THE ADDRESS IN MEDICINE. PMID- 20311314 TI - The Address in Public Health. PMID- 20311315 TI - The Deputy Health Minister. PMID- 20311316 TI - Editorial Notes. PMID- 20311317 TI - Letter from A. B. Macallum. PMID- 20311318 TI - The Medical Society of Nova Scotia. PMID- 20311319 TI - Presidential Address. PMID- 20311320 TI - Cardiac Disease with extensive Venous and Cardiac Thrombosis. PMID- 20311321 TI - Observations on Flying Sickness, with special Reference to its Diagnosis. PMID- 20311322 TI - The Care Of Military Mental Cases. PMID- 20311323 TI - Shakespeare as a guide in the Art and Practice of Medicine. PMID- 20311324 TI - Treatment Of Burns By Tincture Of Iodine. PMID- 20311325 TI - Cranioplasty. PMID- 20311326 TI - On Backward Displacements of the Uterus. PMID- 20311327 TI - A New Start. PMID- 20311328 TI - A Military Psychopathic Hospital. PMID- 20311329 TI - Wax Models for the National War Museum. PMID- 20311330 TI - The Resolutions Passed at the Quebec Meeting. PMID- 20311331 TI - Editorial notes. PMID- 20311333 TI - Description of a Series of Wax Models Made by Major Lessore for the Canadian Government at the Canadian Hospital at Orpington, Kent. PMID- 20311332 TI - Letter from J. C. Connell. PMID- 20311334 TI - Report on Material Received for the Canadian National War Museum from the Royal College of Surgeons, London. PMID- 20311335 TI - Notes on Housing and Town Planning. PMID- 20311336 TI - Internal Hydrocephalus and Xanthochromia of the Spinal Fluid. PMID- 20311337 TI - State Medicine and Rehabilitation. PMID- 20311338 TI - A Report on the Comparison of Kolmer's Modification of the Original Wassermann Test and No. 4 Method as Recommended by the Medical Research Committee. PMID- 20311339 TI - Rupture of Left Cardiac Ventricle. PMID- 20311340 TI - Epidemiology and Recent Epidemics. PMID- 20311341 TI - On Diet and Nutrition. PMID- 20311342 TI - Change in the Laws Regarding Patent Medicines. PMID- 20311343 TI - On Scientific Research. PMID- 20311344 TI - Letter from Alexander McPhedran. PMID- 20311345 TI - The Practical Significance of a Small Amount of Sugar in Urine. PMID- 20311346 TI - The After Effects of Chlorine Gas Poisoning. PMID- 20311347 TI - Postural Albuminuria. PMID- 20311348 TI - On Acidosis. PMID- 20311349 TI - Surgical Efficiency in an Army Medical Service. PMID- 20311351 TI - Town Planning and Civic Authorities. PMID- 20311350 TI - Tick Caused Paralysis. PMID- 20311352 TI - Mental Hygiene in Relation to Social Hygiene. PMID- 20311353 TI - Multiple Infarcts of the Spleen in Malignant Endocarditis, Rupture of the Spleen and Peritonitis. PMID- 20311354 TI - The Practical Aspects of Quarantine for Influenza. PMID- 20311356 TI - Mental Tests in Practice. PMID- 20311355 TI - Treatment of Influenza. PMID- 20311357 TI - War Surgery-Perforating Gunshot Wound of the Face with Extensive Destruction of the Superior Maxillae. PMID- 20311358 TI - Retiring President's Address. PMID- 20311359 TI - Mental Excitement in a Psychopathic Hospital-Its Prevention and Care. PMID- 20311361 TI - The Resignation of Sir Andrew Macphail. PMID- 20311360 TI - Bacillus Coli Infection of the Kidney. PMID- 20311362 TI - The Departure of Professor Adami. PMID- 20311364 TI - High Protein Diet as a Factor in the Production of Nephritis. PMID- 20311363 TI - The New Dentistry. PMID- 20311366 TI - Newer Methods in the Diagnosis of Thyroid Disorders. PMID- 20311365 TI - Editorial Note. PMID- 20311367 TI - Hypertrophic Pyloric Stenosis in Infants. PMID- 20311368 TI - Modern Views on Asthma in Children. PMID- 20311369 TI - Aequanimitas: in the bag. PMID- 20311370 TI - Myositis ossificans progressiva. PMID- 20311371 TI - Air-borne fungi and respiratory allergy. PMID- 20311372 TI - Fraud in science. PMID- 20311373 TI - The language of medicare. PMID- 20311374 TI - The canadian contribution to the world health organization. PMID- 20311375 TI - Remote control. PMID- 20311376 TI - The canadian contribution to the world health organization. PMID- 20311377 TI - Biological warfare. PMID- 20311378 TI - Current views on pesticides. PMID- 20311379 TI - Current standards in reported drug trials. PMID- 20311380 TI - Current standards in reported drug trials. PMID- 20311381 TI - Identification of unidentified tablets and capsules. PMID- 20311383 TI - Bleeders take heart. PMID- 20311382 TI - Original work by family physicians. PMID- 20311384 TI - Fair paradise. PMID- 20311385 TI - Chinese restaurant syndrome. PMID- 20311387 TI - The multidiscipline approach to treatment. PMID- 20311386 TI - Medical stenography. PMID- 20311388 TI - Adrenal steroid therapy in neurological disease. PMID- 20311390 TI - DOMINION INCOME TAX RETURNS by Members of the Medical Profession. PMID- 20311389 TI - Prisoners of war. PMID- 20311391 TI - Lexicon of libation. PMID- 20311393 TI - Cheap drugs. PMID- 20311392 TI - Drug costs. PMID- 20311394 TI - The neurosciences. PMID- 20311395 TI - Diet and heart disease. PMID- 20311396 TI - Clinical trial of a broad-spectrum antimicrobial preparation in vaginitis. PMID- 20311397 TI - Use of azostix for the determination of blood urea nitrogen. PMID- 20311398 TI - One Doctor's Taxes. PMID- 20311399 TI - New pharmaceuticals. PMID- 20311400 TI - Indian and eskimo health. PMID- 20311401 TI - "Money matters". PMID- 20311402 TI - Prisoners of war. PMID- 20311403 TI - The big leagues of medical journalism. PMID- 20311404 TI - The outlook for the economy and the stock market. PMID- 20311405 TI - Vaccinial therapy of verrucae. PMID- 20311406 TI - Subdural effusions in infants. PMID- 20311407 TI - Farmer's Lung. PMID- 20311408 TI - Classified advertisements. PMID- 20311410 TI - Random sampling. PMID- 20311409 TI - Reading disability. PMID- 20311411 TI - Current standards in reported drug trials. PMID- 20311412 TI - Atypical facial pain. PMID- 20311413 TI - Fringe benefits. PMID- 20311414 TI - C.m.a.R.s.p.-C.m.a.I.f. Quarterly financial report. PMID- 20311415 TI - Medical stenography. PMID- 20311416 TI - Hold the anglophone! PMID- 20311417 TI - Northealth. PMID- 20311418 TI - Old age security. PMID- 20311419 TI - Low interest loans to establish medical practice. PMID- 20311420 TI - The "saturday night syndrome". PMID- 20311421 TI - Barefoot doctors. PMID- 20311422 TI - Methods of delivery of medical care. PMID- 20311423 TI - Trauma rounds at the montreal general hospital. PMID- 20311424 TI - Hematology. PMID- 20311425 TI - Mutual improvement. PMID- 20311426 TI - A sea of baffle-gab. PMID- 20311427 TI - Report from Ottawa. PMID- 20311429 TI - Advancing senescence. PMID- 20311428 TI - The editor resigns. PMID- 20311430 TI - Weekly or fortnightly publication. PMID- 20311431 TI - Medical stenography: a stenographer replies. PMID- 20311432 TI - What the man said. PMID- 20311434 TI - The R.s.p. Common stock fund. PMID- 20311433 TI - Canadian paediatric society: use of anti-rh immune globulin. PMID- 20311435 TI - Drug costs. PMID- 20311437 TI - Manpower metamorphosis. PMID- 20311436 TI - The caldwell-o'sullivan duel: a prelude to the founding of the montreal general hospital. PMID- 20311438 TI - C.m.a.R.s.p.-C.m.a.I.f. Quarterly financial report. PMID- 20311439 TI - Supervoltage radiation treatment in advanced cancer of the uterine cervix. PMID- 20311440 TI - Request for hormone-producing tumour material. PMID- 20311442 TI - Misleading advertising. PMID- 20311441 TI - Drug costs. PMID- 20311443 TI - Occupational pulmonary mycoses and toxomycoses. PMID- 20311445 TI - A sea of baffle-gab. PMID- 20311444 TI - Distaff doings. PMID- 20311446 TI - Sudden death in infancy. PMID- 20311447 TI - Incidence of rh immunization. PMID- 20311448 TI - Hazards and dangers of exchange transfusion. PMID- 20311449 TI - Decisions, decisions. PMID- 20311450 TI - The Canadian Medical Association Retirement Savings Plan Fund Manager's Report for July 1969. PMID- 20311451 TI - Evolution of the treatment of shoulder dislocation. PMID- 20311452 TI - Medicine's Logo. PMID- 20311453 TI - [Not Available]. PMID- 20311454 TI - Laboratory AIDS for the study of hemostasis. PMID- 20311455 TI - Some additional thoughts on residency training. PMID- 20311456 TI - Preoperative bleeding and clotting time. PMID- 20311457 TI - Some additional thoughts on residency training. PMID- 20311458 TI - The first woman head of a department. PMID- 20311460 TI - Professional venery. PMID- 20311459 TI - Reading disability. PMID- 20311461 TI - Mediverse. PMID- 20311462 TI - The C.m.a.R.s.p. Common stock fund. PMID- 20311463 TI - Journal frequency. PMID- 20311465 TI - Family practice psychiatry. PMID- 20311464 TI - Canadian association of neurological and neurosurgical nurses. PMID- 20311466 TI - Heraldic hiatus. PMID- 20311467 TI - Trans-Canada medical plans. PMID- 20311468 TI - Ophthalmologist-anesthetist co-operation in intraocular surgery. PMID- 20311469 TI - New a.s.a. Regulations. PMID- 20311471 TI - Pieces of paper. PMID- 20311470 TI - Radiation treatment in cancer of cervix. PMID- 20311472 TI - C.m.a.R.s.p.-C.m.a.I.f. Quarterly report, june 1-august 31, 1969. PMID- 20311473 TI - The case for artificial sweeteners. PMID- 20311474 TI - About medicare-gerlad waring. PMID- 20311475 TI - Munchausen'S syndrome. PMID- 20311476 TI - First total pneumonectomy for cancer of bronchus. PMID- 20311477 TI - Smallpox vaccination. PMID- 20311478 TI - Ethos and techne. PMID- 20311480 TI - A new start. PMID- 20311479 TI - London letter. PMID- 20311481 TI - The journal. PMID- 20311482 TI - Shakespeare as a guide in the art of medicine. PMID- 20311483 TI - Comment: economic council of Canada interim report on competition policy. PMID- 20311484 TI - The caldwell-o'sullivan duel. PMID- 20311485 TI - Suspected adverse reaction to measles virus vaccine. PMID- 20311486 TI - Unsolicited drug samples. PMID- 20311487 TI - The credit side of the journal. PMID- 20311488 TI - Gallbladder disease in newfoundland. PMID- 20311489 TI - Multiphasic screening programs. PMID- 20311490 TI - Smallpox vaccination. PMID- 20311491 TI - Rheumatoid arthritis. PMID- 20311492 TI - Appeal for physicians. PMID- 20311493 TI - Treatment of burns. PMID- 20311495 TI - On priorities. PMID- 20311494 TI - Phenylketonuria screening program. PMID- 20311496 TI - Diagnosis by gastroscopy. PMID- 20311497 TI - Lancet performance fund limited. PMID- 20311498 TI - Canadian colloquy. PMID- 20311499 TI - Medicare; The DDT Controversy. PMID- 20311500 TI - London letter. PMID- 20311502 TI - Resolutions passed at the quebec meeting. PMID- 20311501 TI - Human heart transplantation: report of a case. PMID- 20311503 TI - Presidential address, 1919. PMID- 20311504 TI - Treatment of burns. PMID- 20311505 TI - Relative terms. PMID- 20311506 TI - Rheumatoid arthritis. PMID- 20311507 TI - London letter. PMID- 20311508 TI - Town planning and civic authorities. PMID- 20311510 TI - Of balloons and biological statistics. PMID- 20311509 TI - A plea for experimentation in medical education. PMID- 20311511 TI - Allergic reactions: following patent blue dye injection. PMID- 20311513 TI - Football hero. PMID- 20311512 TI - Lancet performance fund limited. PMID- 20311514 TI - Intimations of mortality. PMID- 20311516 TI - Role of viruses in neoplastic and degenerative disease. PMID- 20311515 TI - Incidental appendectomy. PMID- 20311517 TI - Information sought on dr. Wm. Barnhardt. PMID- 20311518 TI - Cyclamates: government reaction. PMID- 20311519 TI - London letter. PMID- 20311520 TI - London letter. PMID- 20311521 TI - Trauma rounds. PMID- 20311522 TI - Arthrogryposis Multiplex Congenita with Potter's Syndrome. PMID- 20311523 TI - Medical examination or fitness testing? PMID- 20311524 TI - A litter of letters. PMID- 20311525 TI - L.m.f. PMID- 20311526 TI - C.M.A.'s Income Tax Committee. PMID- 20311527 TI - Paradox within paradox. PMID- 20311528 TI - The costing out of doctors and hospitals. PMID- 20311530 TI - C.m.a. Preliminary statement on governmental study: some serious omissions in those task force reports on health service costs. PMID- 20311529 TI - London letter. PMID- 20311531 TI - Yesterday's Medicine: The Resignation of Sir Andrew Macphail. PMID- 20311532 TI - C.m.a.R.s.p. And C.m.a.I.f. Quarterly report, november 30, 1969. PMID- 20311533 TI - That tired feeling. PMID- 20311534 TI - Mortality Rate Shocks M.P.'s. PMID- 20311535 TI - Death from cold. PMID- 20311536 TI - Nocturnal enuresis. PMID- 20311538 TI - In defence of dogmatism. PMID- 20311537 TI - Leukemia in Saskatchewan. PMID- 20311539 TI - London letter. PMID- 20311540 TI - Yesterday's Medicine: The Ontario Temperance Act. PMID- 20311541 TI - Proper storage of insulin preparations. PMID- 20311542 TI - The seventies: medicine by parkinsonian precept. PMID- 20311543 TI - London letter. PMID- 20311544 TI - Timeo danaos. PMID- 20311545 TI - Infection associated with intravenous catheters. PMID- 20311546 TI - Nocturnal enuresis. PMID- 20311547 TI - Therapeutic abortion. PMID- 20311548 TI - Salivary gland reaction to phenylbutazone. PMID- 20311549 TI - Inflation: C.m.a. Urges members to practise voluntary restraint. PMID- 20311550 TI - Selective coronary angiography using a percutaneous femoral technique. AB - Successful use, in 650 patients over a period of two years, of a percutaneous femoral technique of selective coronary angiography is described. This technique is carried out with the use of mouldable, manually preshaped polyethylene catheters. Preparation of the material and the different steps of the technique are discussed. Excellent flexibility and plastic memory of this catheter material allow easy, rapid and consistent percutaneous insertion and removal of catheters and intubation of the coronary arteries. PMID- 20311551 TI - His honour. PMID- 20311553 TI - Journal article influences decision for massive nutritional survey. PMID- 20311552 TI - And then there were nine! PMID- 20311554 TI - Ottawa drug authorities look for better "pill". PMID- 20311556 TI - The Pill: Thousands of Canadian women have been needlessly upset. PMID- 20311555 TI - London letter. PMID- 20311557 TI - W.o., 1849-1919-. PMID- 20311558 TI - Diuretics in cardiac edema. PMID- 20311559 TI - The halothane controversy. PMID- 20311560 TI - Chemical treatment of xanthelasma. PMID- 20311562 TI - The politics of the pill. PMID- 20311561 TI - London letter. PMID- 20311564 TI - Who's Afraid? PMID- 20311563 TI - C.m.a. Asks for freeze at 1969 level of fees. PMID- 20311565 TI - Yesterday's Medicine: The Winnipeg Epidemic of Encephalitis Lethargica. PMID- 20311566 TI - I told you so. PMID- 20311567 TI - Food & drug suspicions force hard decisions. PMID- 20311568 TI - White paper proposals on tax reforms. PMID- 20311569 TI - Yesterday's Medicine: On the Therapeutic Value of Alcohol. PMID- 20311570 TI - Drugs and dreams. PMID- 20311571 TI - The halothane controversy. PMID- 20311572 TI - Late failure in cadaveric renal allografts. PMID- 20311573 TI - Amphetamine abuse. PMID- 20311575 TI - Carriage of oxygen equipment by physicians. PMID- 20311574 TI - In defence of dogmatism. PMID- 20311576 TI - The sparce index: medical excellence or drug dependence. PMID- 20311578 TI - Nocturnal enuresis. PMID- 20311579 TI - London letter. PMID- 20311577 TI - Payments for examinations for disability under the Canada pension plan. PMID- 20311581 TI - Minister pleads for restraint on fee schedule increases. PMID- 20311580 TI - L-dopa No Aphrodisiac. PMID- 20311582 TI - Medicare election issue. PMID- 20311583 TI - DOMINION INCOME TAX RETURNS by Members of the Medical Profession. PMID- 20311585 TI - Yesterday's Medicine: Influenza Again Epidemic. PMID- 20311584 TI - Anyone for caicos? PMID- 20311586 TI - Abortion. PMID- 20311587 TI - Therapeutic abortion. PMID- 20311588 TI - Observations on medical practice. PMID- 20311589 TI - The dream. PMID- 20311590 TI - The seventies: medicine by parkinsonian precept. PMID- 20311591 TI - The seventies: medicine by parkinsonian precept. PMID- 20311592 TI - Therapeutic effectiveness bugs drug officials. PMID- 20311593 TI - Fact finding force tackles pill problem. PMID- 20311594 TI - Canadian air cleanup still ;under consideration'. PMID- 20311595 TI - Carrier trouble. PMID- 20311596 TI - Apologia. PMID- 20311598 TI - Therapeutic breakthrough. PMID- 20311597 TI - London letter. PMID- 20311599 TI - Medical miscellany. PMID- 20311600 TI - Is there a computer in your future? PMID- 20311601 TI - Ottawa offers grants to aid computerization. PMID- 20311603 TI - C.m.a.R.s.p., C.m.a.I.f. And lancet performance fund quarterly report. PMID- 20311602 TI - London letter. PMID- 20311604 TI - Yesterday's Medicine. PMID- 20311605 TI - Fractures of the facial skeleton. PMID- 20311606 TI - Fractures of the facial skeleton. PMID- 20311607 TI - Yesterday'S medicine: the genesis, classification, interrelationships and clinical diagnosis of disease. PMID- 20311608 TI - Risk From Pill Less Than risk Without Pill. PMID- 20311609 TI - New research group tackles transplant problems. PMID- 20311610 TI - F.d.d. Scientists agree with u.k. ;Pill' findings. PMID- 20311611 TI - London letter. PMID- 20311612 TI - Yesterday'S medicine: salvarsan in syphilis. PMID- 20311613 TI - The general secretary retires. PMID- 20311614 TI - Physicians' incomes. PMID- 20311615 TI - Yesterday'S medicine: the ontario medical association reorganization. PMID- 20311616 TI - Them as can. PMID- 20311618 TI - London letter. PMID- 20311617 TI - Agreement with provinces easier than with red china. PMID- 20311619 TI - Yesterday'S medicine: chronic intestinal stasis. PMID- 20311620 TI - Medullary sponge kidney. PMID- 20311622 TI - Request for hormone-producing tumour material. PMID- 20311621 TI - "Au pair". PMID- 20311624 TI - Gregor Johann mendel. PMID- 20311623 TI - Endurance fitness. PMID- 20311625 TI - Yesterday'S medicine: phosphorus as a therapeutic agent. PMID- 20311626 TI - Generic equivalency. PMID- 20311627 TI - London letter. PMID- 20311629 TI - Ottawa tunes its ears to voluntary agencies. PMID- 20311628 TI - What you do about OCs is up to you as MDs. PMID- 20311630 TI - Yesterday'S medicine: the union of septic compound fractures. PMID- 20311631 TI - Yesterday'S medicine: biography of sir william osler. PMID- 20311632 TI - Alport's Syndrome. PMID- 20311633 TI - Fire watching. PMID- 20311635 TI - Yesterday'S medicine: the union of septic compound fractures. PMID- 20311634 TI - Yesterday'S medicine: the union of septic compound fractures. PMID- 20311636 TI - Therapeutic abortion. PMID- 20311637 TI - Let us Stay with the Patient! PMID- 20311638 TI - Oecumenical oecology. PMID- 20311640 TI - M.d.s, hospitals criticized for unrealized expectations. PMID- 20311639 TI - F.d.d., C.m.a. Play pill cool; both agree no emergency. PMID- 20311641 TI - London letter. PMID- 20311643 TI - Come out from under that bed. PMID- 20311642 TI - Yesterday'S medicine: prolongation of life. PMID- 20311644 TI - Yesterday'S medicine: a plea for the sphincter ani. PMID- 20311645 TI - C.M.A. Anti-abortion. PMID- 20311646 TI - London letter. PMID- 20311647 TI - First move to train doctor assistants. PMID- 20311648 TI - Social education in drugs new function for f.d.d. PMID- 20311649 TI - Politicians hostile to fee increases. PMID- 20311651 TI - Yesterday'S medicine: heat and infant mortality. PMID- 20311650 TI - Genetic aspects of mental retardation. PMID- 20311652 TI - Doctors asked to curb costs of hospital care and drugs. PMID- 20311653 TI - Ruling on phenacetin poses dilemma for f.d.d. PMID- 20311654 TI - Basford presses druggists with socialization hint. PMID- 20311655 TI - London letter. PMID- 20311656 TI - The Queen's Birthday. PMID- 20311657 TI - Electroencephalotherapy. PMID- 20311659 TI - Possible lethal reaction between nardil and dextromethorphan. PMID- 20311658 TI - The pioneer spirit. PMID- 20311660 TI - Yesterday'S medicine: medical education. PMID- 20311661 TI - Where're You From? PMID- 20311662 TI - Political Snafus Surround Release of LeDain Report. PMID- 20311663 TI - London letter. PMID- 20311664 TI - Yesterday'S medicine: pituitrin. PMID- 20311665 TI - Multiphasic screening. PMID- 20311666 TI - Abortion law reform. PMID- 20311668 TI - W.o. & f.B.B. PMID- 20311667 TI - Yesterday'S medicine: the anti-tuberculosis campaign-a social campaign-the role of the government-the role of private effort. PMID- 20311669 TI - Mercury, lead hazards from industrial growth. PMID- 20311670 TI - New f.d.d. Allergy tests have many advantages. PMID- 20311671 TI - Ottawa Will Monitor Nation's Food Supply. PMID- 20311673 TI - Abortion in Canada. PMID- 20311672 TI - London letter. PMID- 20311675 TI - I remember osler. PMID- 20311674 TI - Recent developments in cardiac surgery. PMID- 20311676 TI - Recollections of w.o. PMID- 20311677 TI - Oecumenical oecology. PMID- 20311678 TI - Oecumenical oecology. PMID- 20311679 TI - Oecumenical oecology. PMID- 20311680 TI - Crossmatching with rh immune globulin. PMID- 20311681 TI - Crossmatching with rh immune globulin. PMID- 20311682 TI - You and the ads. PMID- 20311683 TI - Yesterday'S medicine: presidential address. PMID- 20311684 TI - London letter. PMID- 20311685 TI - Congenital rubella syndrome. PMID- 20311686 TI - Congenital rubella syndrome. PMID- 20311687 TI - Medical services at pop festivals. PMID- 20311688 TI - Unnecessary laboratory tests. PMID- 20311689 TI - Payment for chiropractic services. PMID- 20311690 TI - Therapeutic abortion. PMID- 20311691 TI - Yesterday'S medicine: surgical gynecology. PMID- 20311692 TI - The bidet circuit. PMID- 20311693 TI - London letter. PMID- 20311695 TI - Neurosurgical manpower in Canada. PMID- 20311694 TI - The value of counting developmental anomalies. PMID- 20311696 TI - Peritoneal dialysis. PMID- 20311697 TI - Human rights and advertising. PMID- 20311698 TI - Rehabilitation in chronic hospitals. PMID- 20311699 TI - Case reports-a breach of confidence. PMID- 20311700 TI - Midsummer 1970. PMID- 20311701 TI - London letter. PMID- 20311702 TI - Abortion. PMID- 20311703 TI - Abortion. PMID- 20311704 TI - Abortion. PMID- 20311705 TI - Abortion. PMID- 20311706 TI - Abortion. PMID- 20311708 TI - On the death of a student. PMID- 20311707 TI - Payment for chiropractic services. PMID- 20311709 TI - Yesterday'S medicine: psychiatry and internal medicine. PMID- 20311710 TI - Seatmates. PMID- 20311711 TI - London letter. PMID- 20311712 TI - Closing remarks / conclusion. PMID- 20311713 TI - The room at the bottom of the stairs. PMID- 20311714 TI - London letter. PMID- 20311715 TI - Yesterday'S medicine: relationship between state and practitioner in England. PMID- 20311716 TI - Publish and perish? PMID- 20311717 TI - Immigrants and their children. PMID- 20311718 TI - Oxytocin-induced Water Intoxication. PMID- 20311719 TI - Neurofibromatosis and hyperparathyroidism. PMID- 20311721 TI - Base railings. PMID- 20311720 TI - Rehabilitation in chronic hospitals. PMID- 20311722 TI - London letter. PMID- 20311723 TI - Abortion. PMID- 20311724 TI - Abortion. PMID- 20311725 TI - Therapeutic abortion in a canadian city. PMID- 20311726 TI - Housewarmings. PMID- 20311727 TI - London letter. PMID- 20311728 TI - Training in community health. PMID- 20311729 TI - Addict alert. PMID- 20311730 TI - London letter. PMID- 20311731 TI - Yesterday'S medicine: the improved and larger journal. PMID- 20311732 TI - Too many children or too many pediatricians. PMID- 20311733 TI - Manifestations of pinworms. PMID- 20311735 TI - Environmental pollution. PMID- 20311734 TI - Abortion. PMID- 20311736 TI - Environmental pollution. PMID- 20311737 TI - Felicity. PMID- 20311738 TI - London letter. PMID- 20311739 TI - Voluntary sterilization. PMID- 20311741 TI - Picture from the past. PMID- 20311740 TI - London letter. PMID- 20311742 TI - The new C.m.a. Code of ethics. PMID- 20311743 TI - MEDLARS magic. PMID- 20311744 TI - London letter. PMID- 20311746 TI - Fitness to fly? PMID- 20311745 TI - Studies of survivors of myocardial infarction. PMID- 20311747 TI - Fitness to fly. PMID- 20311748 TI - Cps'71. PMID- 20311749 TI - An agent transmitting Crohn's disease. PMID- 20311751 TI - Conditional contrition. PMID- 20311750 TI - Physician's Assistant. PMID- 20311752 TI - London letter. PMID- 20311754 TI - My friend tony. PMID- 20311753 TI - Cluster migraine. PMID- 20311755 TI - Pictorial protest. PMID- 20311756 TI - Biography of Dr. Ray F. Farquharson planned. PMID- 20311757 TI - London letter. PMID- 20311759 TI - Federal income tax returns by members of the medical profession. PMID- 20311758 TI - The part-time prosector. PMID- 20311760 TI - Winter garden. PMID- 20311761 TI - London letter. PMID- 20311762 TI - A 93-year-old writes about abortion. PMID- 20311763 TI - Specialists Required by CARE/MEDICO. PMID- 20311764 TI - Brownian movement. PMID- 20311765 TI - London letter. PMID- 20311766 TI - Multiple rib fractures. PMID- 20311767 TI - Fee splitting and the Code of Ethics. PMID- 20311768 TI - "April is the Cruellest Month". PMID- 20311769 TI - London letter. PMID- 20311771 TI - Price of progress. PMID- 20311772 TI - C.m.a. Code of ethics. PMID- 20311770 TI - Vaccination certificates. PMID- 20311773 TI - Price of progress. PMID- 20311774 TI - Profit from losers. PMID- 20311776 TI - A miasma of ministers. PMID- 20311775 TI - U.w.I. Medical graduates. PMID- 20311777 TI - London letter. PMID- 20311778 TI - Specialist appointment in indonesia. PMID- 20311779 TI - Recruits sought for Vietnam medical program. PMID- 20311780 TI - Atraumatic endotracheal tube. PMID- 20311781 TI - Some thoughts on medical education. PMID- 20311782 TI - Abortion. PMID- 20311783 TI - The establishment. PMID- 20311785 TI - Need for accurate income data. PMID- 20311784 TI - London letter. PMID- 20311787 TI - Birds of a feather. PMID- 20311786 TI - Dietary sugar and myocardial infarction. PMID- 20311788 TI - On the move. PMID- 20311790 TI - Analysis of illicit drug samples. PMID- 20311789 TI - London letter. PMID- 20311791 TI - A key to scientific research literature. PMID- 20311793 TI - A view From the Office Window. PMID- 20311792 TI - Role of the inhalation therapist. PMID- 20311794 TI - Thinking back. PMID- 20311795 TI - Sudden death from ischemic heart disease in ontario. AB - It is possible that there is a systematic geographical variation in the proportion of deaths from ischemic heart disease that occur suddenly, and that this variation may be causally related to water hardness or some other environmental factor. Three indices of sudden death have been examined; each showed a correlation with water hardness that was of similar sign and magnitude. A detailed examination of 1686 deaths occurring in residents of two cities which differ widely in the hardness of their water supply confirmed that in deaths ascribed to heart disease the proportion of sudden deaths was higher (by 20-30%) in the northern (soft-water) city than in the southern (hard-water) city. PMID- 20311796 TI - Blood donations by young women. PMID- 20311797 TI - The abortion situation. PMID- 20311799 TI - Cardiac Arrest remembered. PMID- 20311798 TI - The abortion situation. PMID- 20311800 TI - Fearsome frailty. PMID- 20311802 TI - A pride of presidents. PMID- 20311801 TI - Criticism. PMID- 20311803 TI - The C.M.A. resolutions on abortion. PMID- 20311804 TI - Twenty-fifth world medical assembly. PMID- 20311805 TI - We need your help. PMID- 20311806 TI - Motor motif. PMID- 20311808 TI - How aspirin works. PMID- 20311807 TI - The long view. PMID- 20311809 TI - Throat infections in children. PMID- 20311810 TI - Columnar epithelium. PMID- 20311811 TI - Soul searching. PMID- 20311812 TI - The way I see it. PMID- 20311813 TI - Musings. PMID- 20311814 TI - Legal abortion. PMID- 20311815 TI - Disseminated intravascular coagulation. PMID- 20311816 TI - B.M.A. rate increases. PMID- 20311817 TI - Nurse, nurse! PMID- 20311818 TI - Fairy rings. PMID- 20311820 TI - Unnecessary x-rays. PMID- 20311819 TI - Antiviral vaccine programs. PMID- 20311821 TI - C.M.A. stand on abortion. PMID- 20311822 TI - Early repair of rectovaginal fistula. PMID- 20311823 TI - Canine quartet. PMID- 20311825 TI - Ketamine - a new anesthetic. PMID- 20311824 TI - Unnecessary x-rays. PMID- 20311826 TI - The long view. PMID- 20311827 TI - Ethanol metabolism in various racial groups. PMID- 20311828 TI - Unexpected infant death. PMID- 20311829 TI - Riot casualties in Belfast. PMID- 20311830 TI - Experiences with an artificial heart. PMID- 20311831 TI - The management of dementia rosae. PMID- 20311832 TI - The Gellman analysis. PMID- 20311833 TI - An Osler anecdote. PMID- 20311834 TI - Stargazing. PMID- 20311835 TI - Wahlverwandschaften. PMID- 20311836 TI - Who died between 1701 and 1740? PMID- 20311837 TI - Foreword. PMID- 20311838 TI - Introductory remarks. PMID- 20311840 TI - Now it can be told. PMID- 20311839 TI - Concluding remarks. PMID- 20311841 TI - The oldest profession? PMID- 20311843 TI - Hunt Commission report. PMID- 20311842 TI - Soul searching. PMID- 20311844 TI - Tout fini. PMID- 20311845 TI - The challenge of life. PMID- 20311846 TI - Acute myocardial infarction. PMID- 20311847 TI - In support of D.D.T. PMID- 20311849 TI - Steamboating. PMID- 20311848 TI - Changing perspectives on professionalism. PMID- 20311850 TI - Cracking the primary contact barrier. PMID- 20311851 TI - Medical student enrolment 1969-70. PMID- 20311853 TI - Lithium intoxication. PMID- 20311852 TI - Lithium intoxication. PMID- 20311854 TI - Community health centre project. PMID- 20311855 TI - To serve you better. PMID- 20311856 TI - Non-ketotic hyperosmolar coma. PMID- 20311857 TI - Non-ketotic hyperosmolar coma. PMID- 20311858 TI - Outpatient abortions. PMID- 20311859 TI - Neurotic excoriations. PMID- 20311860 TI - Neurotic excoriations. PMID- 20311861 TI - Mangled and missed messages. PMID- 20311862 TI - Dermatologists, too, get into trouble. PMID- 20311863 TI - Monoamine oxidase inhibitors. PMID- 20311864 TI - Ave, a.d.k. PMID- 20311865 TI - The oldest profession? PMID- 20311866 TI - Nevoid basal cell carcinoma. PMID- 20311867 TI - The Gellman analysis. PMID- 20311868 TI - The oldest profession? PMID- 20311869 TI - Nevoid basal cell carcinoma. PMID- 20311870 TI - Double-blind studies. PMID- 20311871 TI - The way Groucho Marx saw it. PMID- 20311872 TI - In support of family life education. PMID- 20311874 TI - Adverse reactions from beer. PMID- 20311873 TI - Korotkov. PMID- 20311875 TI - One-stage prothrombin time. PMID- 20311876 TI - "Before" and "after" photographs. PMID- 20311877 TI - Treatment of intervertebral disc protrusion. PMID- 20311878 TI - Producing more physicians. PMID- 20311879 TI - "She that with poetry is won". PMID- 20311880 TI - The enemy. PMID- 20311881 TI - The elusive master plan. PMID- 20311882 TI - Health services - $$$ - and the future. PMID- 20311883 TI - Earnings of Canadian physicians 1959-69. PMID- 20311884 TI - Enuresis. PMID- 20311885 TI - Enuresis. PMID- 20311887 TI - Enuresis. PMID- 20311886 TI - Enuresis. PMID- 20311888 TI - Unnecessary Morbidity from breast surgery. PMID- 20311889 TI - Ketamine. PMID- 20311890 TI - Glimpses of Chinese medicine. PMID- 20311891 TI - The mills of Cote grind slowly.. PMID- 20311892 TI - When is carelessness blameworthy? PMID- 20311894 TI - Inconsistency or misunderstanding? PMID- 20311893 TI - "Fellowship for all". PMID- 20311895 TI - Recurrent urinary infections. PMID- 20311896 TI - The oldest profession? PMID- 20311897 TI - Another year of decision. PMID- 20311898 TI - Public interest cited as restrictive covenant fails court test in Ontario. PMID- 20311900 TI - A case of MUMPS at Ottawa University. PMID- 20311899 TI - Alberta writes new Act to cover sterilization of mentally deficient. PMID- 20311901 TI - Health care delivery in the "Switzerland of Africa". PMID- 20311902 TI - Quebec physicians draw on services of dietitians. PMID- 20311903 TI - What's New. PMID- 20311904 TI - What is policy? PMID- 20311905 TI - ;Global' payment system for Saskatchewan community clinics. PMID- 20311907 TI - Alberta doctors average $57,728 from Medicare. PMID- 20311906 TI - Allergies, too, cause legal trouble. PMID- 20311908 TI - The ;Craig Case'-how an Edmonton GP became Alberta's cause celebre. PMID- 20311910 TI - What's New. PMID- 20311909 TI - Methadone control guidelines established. PMID- 20311911 TI - Present and future shock. PMID- 20311912 TI - Physicians alone are not to blame. PMID- 20311913 TI - The Ulysses syndrome. PMID- 20311914 TI - Courses in medical English. PMID- 20311915 TI - The Ulysses syndrome. PMID- 20311916 TI - The Ulysses syndrome. PMID- 20311918 TI - DNHW gives go-ahead for national health accreditation commission. PMID- 20311917 TI - The market-place. PMID- 20311919 TI - Dr. Potter prunes student allowances in Ontario. PMID- 20311920 TI - How Saskatchewan's ;community clinic on wheels' helps mentally retarded. PMID- 20311922 TI - Dial-a-doc service aims at easing Montreal's office appointment load. PMID- 20311921 TI - CASS grows bigger-but it's all muscle, no flab. PMID- 20311923 TI - What's New. PMID- 20311924 TI - Reflections on tomorrow's breakthrough. PMID- 20311925 TI - Simplified isoniazid acetylator phenotyping. PMID- 20311926 TI - Learning disability. PMID- 20311927 TI - Pill popping population. PMID- 20311928 TI - Consents-what every hospital and physician should know. PMID- 20311929 TI - What's New. PMID- 20311930 TI - "Fellowship for all". PMID- 20311931 TI - Editorial anonymity. PMID- 20311932 TI - Rifampin. PMID- 20311934 TI - CNA's slashing attack on chiropractors. PMID- 20311935 TI - New Coroners Act gives protection to witnesses and jurors in inquests. PMID- 20311936 TI - Alberta mental health legislation receives mixed reception. PMID- 20311937 TI - Vaccination - a battleground where apathy is greater enemy than disease. PMID- 20311939 TI - A light in the forest for Vancouver neurotics. PMID- 20311938 TI - Calgary's mini-hospital is attracting nationwide attention. PMID- 20311940 TI - "Fellowship for all". PMID- 20311942 TI - Treatment with vitamin E. PMID- 20311941 TI - Tinea faciale. PMID- 20311943 TI - Mineral deficiency. PMID- 20311944 TI - The story of the birth of Canadian Medicare in Saskatchewan and its development during the following ten years (Part III). PMID- 20311945 TI - GPs to benefit most from increased Medicare payments in Saskatchewan. PMID- 20311946 TI - Dr. Craig cleared of charges - but controversy continues. PMID- 20311947 TI - Quebec Medicare shows $8.7 million surplus. PMID- 20311948 TI - Bill would increase medical review powers in Manitoba. PMID- 20311949 TI - What's New. PMID- 20311950 TI - Koch and Fick and others. PMID- 20311951 TI - Hepatic hemorrhage due to eclampsia. PMID- 20311952 TI - Children with chronic asthma. PMID- 20311953 TI - Douchement. PMID- 20311955 TI - Antibody response to live rubella vaccine. PMID- 20311954 TI - Information sought. PMID- 20311957 TI - You don't have to be fat. PMID- 20311956 TI - Clarification of position. PMID- 20311958 TI - Lazy, hazy days. PMID- 20311959 TI - Surgery to recover bullet would violate human rights of bank robbery suspect, Judge rules. PMID- 20311960 TI - Much talk, but Medicare cost sharing agreement remains a very dark horse. PMID- 20311962 TI - Personal financial management (II) - planning your financial strategy. PMID- 20311961 TI - Payment methods at Saskatchewan clinics to be studied. PMID- 20311963 TI - Rh-D isoimmunization. PMID- 20311964 TI - Rh-D isoimmunization. PMID- 20311965 TI - Allergy injections. PMID- 20311966 TI - Amotivational syndrome. PMID- 20311967 TI - "Dirty Harry" syncope. PMID- 20311968 TI - Manners maketh man. PMID- 20311969 TI - In health and in sickness. PMID- 20311970 TI - Issues in abortion. PMID- 20311971 TI - Learning disability. PMID- 20311972 TI - Variations in pension benefits. PMID- 20311973 TI - Aphorisms. PMID- 20311974 TI - A meeting of the minds. PMID- 20311975 TI - Quebec's unfit driver legislation means doctors must report patients. PMID- 20311976 TI - Manitoba prescriptions to carry more details. PMID- 20311977 TI - What's New. PMID- 20311978 TI - Blair clinic symposium. PMID- 20311979 TI - Myrna's four personalities are computerized patient management teaching aids. PMID- 20311980 TI - What's New. PMID- 20311981 TI - Metacarpal cortical measurements. PMID- 20311983 TI - "Dirty Harry" syncope. PMID- 20311982 TI - Faith in healing. PMID- 20311984 TI - GP exchange with South Africa. PMID- 20311986 TI - What the life insurance industry has to offer the physician. PMID- 20311985 TI - The time for all good men.. PMID- 20311987 TI - What's New. PMID- 20311988 TI - Strangulation on the road. PMID- 20311989 TI - Can learning be transmitted? PMID- 20311991 TI - The Ruderman Report - appendix I to the CHC project committee's report. PMID- 20311990 TI - To leave or not to leave. PMID- 20311993 TI - Community health centres - more reaction from the profession to the Hastings Report. PMID- 20311992 TI - Hastings on Hastings: The CHC Project leader discusses his committee's report. PMID- 20311995 TI - Physician politicians stand up to be counted. PMID- 20311994 TI - Do yourself a favour.. PMID- 20311996 TI - Yes, no and don't know. PMID- 20311998 TI - Comparative bioavailability. PMID- 20311997 TI - Comparative bioavailability. PMID- 20311999 TI - Comparative bioavailability. PMID- 20312000 TI - Illusive flattery. PMID- 20312001 TI - "The unholy alliance". PMID- 20312002 TI - Serum triglycerides and aorto-coronary vein grafts. PMID- 20312003 TI - Stimulation without acrimony. PMID- 20312004 TI - East meets West (II) - Chinese medical group tours Canada as guests of CMA. PMID- 20312005 TI - World Medical Association ;now more realistic' in dealing with problems. PMID- 20312007 TI - Saskatchewan announces plans for integrated health science facilities. PMID- 20312006 TI - Commonwealth Medical Association meets in Ghana. PMID- 20312009 TI - What's New. PMID- 20312008 TI - Two projects that show promise of a better deal for Quebec's newborn. PMID- 20312010 TI - Multiple congenital anomalies. PMID- 20312011 TI - Dupuytren's disease. PMID- 20312012 TI - Multiple congenital anomalies. PMID- 20312013 TI - Methadone controls. PMID- 20312014 TI - Spending the tax dollar. PMID- 20312015 TI - Some astronautical questions. PMID- 20312016 TI - What is relative? PMID- 20312017 TI - Teaching hospital completes the picture at University of Western Ontario's health sciences complex. PMID- 20312018 TI - What's New. PMID- 20312019 TI - Special Report-Ontario slashes hospital beds. PMID- 20312020 TI - Hastings on hastings. PMID- 20312021 TI - They come to talk. PMID- 20312022 TI - Regulating the needle.. PMID- 20312023 TI - The stock market and the beginner (I) - first of three articles. PMID- 20312025 TI - Saskatchewan hospitals switch to global budget system. PMID- 20312024 TI - Hospital, medical care cost cutbacks ;a tiger by the tail' says OMA President. PMID- 20312026 TI - Professional associations united in opposition to Quebec's new Bill 30. PMID- 20312027 TI - G. P. Federation calls for full inquiry into Demers case. PMID- 20312028 TI - What's New. PMID- 20312029 TI - Medical care costs related to physician manpower - a new economic theory. PMID- 20312030 TI - 1970 income figures show 11.3 percent increase in net earnings of physicians. PMID- 20312031 TI - What's New. PMID- 20312032 TI - Thirty years onward. PMID- 20312033 TI - Milk and alcohol. PMID- 20312034 TI - Cerebral complications in juvenile rheumatoid arthritis. PMID- 20312035 TI - Management of low back pain. PMID- 20312036 TI - The Sault experience. PMID- 20312037 TI - On the nature and treatment of cancer. PMID- 20312038 TI - Skiing. PMID- 20312039 TI - The generation gap - McCrae and Bethune. PMID- 20312040 TI - The battering child. PMID- 20312041 TI - Irradiation of the hypophysis. PMID- 20312042 TI - American consultants. PMID- 20312043 TI - Bioavailability of digoxin. PMID- 20312044 TI - Professional assessment: A Wing and a prayer are not enough. PMID- 20312045 TI - What's New. PMID- 20312046 TI - Income Tax-MD Style: A Check List to Help You File Your 1972 Tax Return. PMID- 20312047 TI - Learning disability. PMID- 20312048 TI - Dealing with incompetence. PMID- 20312049 TI - The team spirit. PMID- 20312050 TI - Even bureaucrats wonder "why don't We?". PMID- 20312051 TI - What's New. PMID- 20312052 TI - Ontario says it doesn't want a competing hospital system. So where does that leave Medical Inn? PMID- 20312053 TI - Being a doctor - it really isn't easy! PMID- 20312055 TI - History of chiropractic demonstrates opposition to scientific medicine. PMID- 20312054 TI - Don't just hand that new tax form to your accountant - open it first. PMID- 20312057 TI - Freedom to publish in science. PMID- 20312056 TI - What's New. PMID- 20312059 TI - Residency training in anesthesia. PMID- 20312058 TI - Levodopa in Forbes-Albright syndrome. PMID- 20312060 TI - An appeal for kidney donors. PMID- 20312061 TI - The Sault experience. PMID- 20312062 TI - Marijuana research. PMID- 20312063 TI - The Sault experience. PMID- 20312065 TI - The anxious relative syndrome. PMID- 20312064 TI - The royal college. PMID- 20312067 TI - Income reporting on accrual basis required. But you do get a break. PMID- 20312066 TI - The veteran stock market investor. PMID- 20312068 TI - What's New. PMID- 20312069 TI - The way some others see it. PMID- 20312070 TI - The way some others see it. PMID- 20312071 TI - Fifty years of progress. PMID- 20312072 TI - Credibility - the name of the game. PMID- 20312073 TI - [Not Available]. PMID- 20312074 TI - Quebec omnipratitioners launch educational radio and A-V programs. PMID- 20312075 TI - Canadian dentists plan to build new office next to CMA in Ottawa. PMID- 20312076 TI - Ontario Ministry of Health confused as reorganization plan stumbles along. PMID- 20312077 TI - Eight years ago Lester Pearson opened successful campaign for medicare. PMID- 20312078 TI - Seven MDs in Commons. PMID- 20312079 TI - [Not Available]. PMID- 20312080 TI - Amphetamine controls. PMID- 20312081 TI - Marijuana research. PMID- 20312082 TI - Marijuana research. PMID- 20312083 TI - Neurological form of schizophrenia. PMID- 20312084 TI - Neurological form of schizophrenia. PMID- 20312085 TI - Art. PMID- 20312087 TI - Cottages and other second residences: how will your tax-collector view them? PMID- 20312086 TI - Quebec legislation should be amended for effective limits on chiropractic. PMID- 20312088 TI - A study on transfer of functions. PMID- 20312090 TI - Accidents kill 2000 children a year. PMID- 20312089 TI - Mass screening can decrease cancer mortality; logistics still uncertain. PMID- 20312092 TI - How the clinic affected the community. PMID- 20312091 TI - How two physician-operated clinics brought care to remote communities. PMID- 20312093 TI - Review system of physician competence in U.S. seems headed in new direction. PMID- 20312094 TI - Needed attention within medicare plan not possible, some Quebec doctors say. PMID- 20312095 TI - What's New. PMID- 20312097 TI - Complete history and physical examination. PMID- 20312096 TI - Complete history and physical examination. PMID- 20312098 TI - Complete history and physical examination. PMID- 20312100 TI - American consultants. PMID- 20312099 TI - PKU screening. PMID- 20312102 TI - Tar, nicotine content of cigarettes reduced according to new survey. PMID- 20312101 TI - American consultants. PMID- 20312103 TI - British columbia medical association. PMID- 20312104 TI - British columbia medical association. PMID- 20312105 TI - Frequency of hepatitis B antigen. PMID- 20312106 TI - Early breast cancer. PMID- 20312108 TI - An APMR - now what would that be? PMID- 20312107 TI - Enrolment of out-of-province medical students. PMID- 20312110 TI - Real estate for everyone. PMID- 20312109 TI - Health care reorganization becomes vehicle for federal-provincial game. PMID- 20312111 TI - Uniform schedule of immunization recommended for cross-Canada use. PMID- 20312113 TI - One medical place. PMID- 20312112 TI - What's New. PMID- 20312115 TI - [Not Available]. PMID- 20312114 TI - Income properties provide yield, safety, while land investment is a speculation. PMID- 20312116 TI - What's New. PMID- 20312118 TI - What's New. PMID- 20312117 TI - Graduates of baroda medical college. PMID- 20312119 TI - Wherever the traveller goes, IAMAT aims to ensure quality medical aid. PMID- 20312120 TI - Immunization in tuberculosis. PMID- 20312121 TI - Chlorpromazine-induced SLE. PMID- 20312123 TI - It's the professionals who know the pitfalls of big-time real estate. PMID- 20312122 TI - Prepaid group practice combines personal health care services, good organization. PMID- 20312124 TI - What's New. PMID- 20312125 TI - [Not Available]. PMID- 20312126 TI - Blood pressure reduction in "borderline" hypertensives. PMID- 20312127 TI - British columbia medical association. PMID- 20312128 TI - Physician services in remote communities. PMID- 20312129 TI - Nonbacterial pneumonitis with antineoplastic therapy. PMID- 20312130 TI - "Clinical material". PMID- 20312131 TI - Of human life. PMID- 20312132 TI - Fee-for-service. PMID- 20312133 TI - "Write the vision, and make it plain...". PMID- 20312135 TI - AMA launches review of facts broadcast in NBC television documentary on medicine. PMID- 20312134 TI - Changes in adipose tissue and increased serum cholesterol of coronary patients following training. AB - A study was undertaken to investigate whether a physical training effect could be observed in the adipose tissue composition of coronary patients. The results indicated that there was an increase in the proportion of palmitic acid and a decrease in oleic acid. These changes were accompanied by an increase in blood cholesterol. PMID- 20312137 TI - Anti-androgens for sex offenders. PMID- 20312136 TI - [Not Available]. PMID- 20312138 TI - A British report on AID. PMID- 20312139 TI - Nurse practitioners. PMID- 20312141 TI - Nurse practitioners. PMID- 20312140 TI - Behavioural modification in obesity. PMID- 20312142 TI - Nurse practitioners. PMID- 20312143 TI - Poliomyelitis immunization. PMID- 20312144 TI - Fee-for-service. PMID- 20312145 TI - True knot of the umbilical cord in two consecutive pregnancies. PMID- 20312146 TI - Decentralization-an obvious benefit. PMID- 20312148 TI - Real estate is a profitable investment but first spell out the questions. PMID- 20312147 TI - Health services in Ontario correctional system under new direction as urged in Botterrell report. PMID- 20312150 TI - Shorter chemotherapy of tuberculosis. PMID- 20312149 TI - Quebec federations battle to raise pay for physicians. PMID- 20312151 TI - Apmr. PMID- 20312152 TI - Medical findings from Skylab One suggest living in space no serious problem. PMID- 20312153 TI - What's New. PMID- 20312155 TI - Global budget. PMID- 20312154 TI - Global budget. PMID- 20312156 TI - Smallpox vaccination. PMID- 20312158 TI - The Sault experience. PMID- 20312157 TI - Antecedents of myocardial infarction. PMID- 20312159 TI - Witwatersrand graduates. PMID- 20312160 TI - [Not Available]. PMID- 20312161 TI - Unsolicited sampling of all drugs now to come under ban. PMID- 20312162 TI - Geology and disease in Newfoundland. PMID- 20312163 TI - Enuresis. PMID- 20312164 TI - Excessive busyness affects doctors; carelessness results. PMID- 20312165 TI - [Not Available]. PMID- 20312166 TI - Juvenile rheumatoid arthritis. PMID- 20312168 TI - Demonstrations of continued competence would involve much administrative detail. PMID- 20312167 TI - Relationship of age-specific incidence rates to immunological aspects of Hashimoto's thyroiditis. AB - Studies of the age-specific incidence rates of the appearance of Hashimoto's thyroiditis indicate that this disorder appears at random in a genetically preselected population. Following an initial lag in the first few years of life, the disease appears at a constant rate thereafter in this population.The age specific incidence rates were similar to those previously reported for Graves' disease. Moreover, there is considerable evidence implicating cell-mediated immunity in both diseases, with the likelihood of cooperating humoral antibodies as well. It may be hypothesized that the two diseases are primarily due to genetic defects in immunological surveillance, which result in an inability to destroy or control a specific forbidden clone of thymicderived lymphocytes which may arise by normal random mutation. The T-lymphocyte interacts with its complementary antigen (on a hitherto normal thyroid cell), setting up a cell mediated immune response; in addition it may cooperate with bursa-equivalent lymphocytes, which then produce humoral antibodies. It is possible that both cell mediated immunity and humoral antibodies are necessary for the full expression of the disease. PMID- 20312169 TI - Bioavailability: report of the special advisory committee to the health protection branch, DNH&W. PMID- 20312170 TI - Canada's Medical Schools: Western Ontario and Saskatchewan. PMID- 20312171 TI - What's New. PMID- 20312172 TI - [Not Available]. PMID- 20312173 TI - Canada's medical schools: University of Manitoba and McMaster University. PMID- 20312174 TI - China report. PMID- 20312175 TI - Varicose veins and "Trauma Canada". PMID- 20312176 TI - Transmitting a cold. PMID- 20312178 TI - "Cold" white kidney. PMID- 20312177 TI - [Not Available]. PMID- 20312179 TI - "Cold" white kidney. PMID- 20312181 TI - Epilepsy and driving licences. PMID- 20312180 TI - Learning disability. PMID- 20312182 TI - Respiratory disease in young adults. PMID- 20312183 TI - Gas gangrene in civilian practice. PMID- 20312184 TI - Parents of children with cystic fibrosis. PMID- 20312185 TI - The essence of the town-gown gap. PMID- 20312186 TI - What's New. PMID- 20312187 TI - Canada's medical schools: drawings of Queen's and McGill. PMID- 20312188 TI - The Pickering Report; CMAJ begins publication in full - Part I, why and how the study was established. PMID- 20312190 TI - Aphorisms. PMID- 20312189 TI - Psychiatric practice in Canada. PMID- 20312191 TI - Confrontation in manitoba. PMID- 20312192 TI - The Pickering Report, Part II: what the doctors think. PMID- 20312193 TI - What's New. PMID- 20312194 TI - The Scope of a Federal Department of Health. PMID- 20312195 TI - Constitutional Symptoms and Focal Infections of the Genito-Urinary Tract. PMID- 20312196 TI - Tuberculosis of the Kidney and ureter. PMID- 20312197 TI - Indications for and Results of Transfusion. PMID- 20312198 TI - Spasmophilia (Infantile Tetany). PMID- 20312199 TI - Wounds of the Chest. PMID- 20312201 TI - The Public and Malignant Disease. PMID- 20312200 TI - The Problem of the Mentally Defective In the Province of Quebec. PMID- 20312203 TI - The Value of Psychopathic Hospitals. PMID- 20312202 TI - The Medical and Allied Professions as a State Service. PMID- 20312205 TI - Diseases of the Gastro-Intestinal Tract. PMID- 20312204 TI - NEW FACTS, NEW SUGGESTIONS. PMID- 20312206 TI - The Influence of Sir William Osler on Medicine in America. PMID- 20312208 TI - Focal Infections: Ileal and Colonic Stasis. PMID- 20312207 TI - The Pathological Collections of the late Sir William Osler. PMID- 20312209 TI - Chronic Intestinal Stasis. PMID- 20312210 TI - The Winnipeg Epidemic of Encephalitis Lethargica. PMID- 20312211 TI - Obstetric Paralysis-Its Cause and Treatment. PMID- 20312213 TI - Blood Transfusion. PMID- 20312212 TI - The Treatment of Empyema in Lobar Pneumonia by Early Aspiration. PMID- 20312214 TI - Notes on Two Cases of Peculiar Medical Interest: 1. Syphilitic Aortic Insufficiency. 2. Cerebro-spinal Fever supervening upon Erythema Nodosum. PMID- 20312215 TI - Encephalitis Lethargica. PMID- 20312216 TI - The Death of Sir William Osler. PMID- 20312217 TI - System in the Care of the Sick. PMID- 20312218 TI - Letter from Gordon Bates. PMID- 20312220 TI - Letter from Murray MacLaren. PMID- 20312219 TI - Letter from A. B. Macallum. PMID- 20312221 TI - OEdemas, not of Nephritic Origin, in Infancy and Childhood. PMID- 20312222 TI - Recent Additions to our Knowledge of Infantine Scurvy. PMID- 20312223 TI - Sir William Osler, Bart., M.D., F.R.S., etc. PMID- 20312224 TI - Abstract of Presidential Address, Manitoba Medical Association. PMID- 20312225 TI - Presidential Address, Alberta Medical Association. PMID- 20312226 TI - Plasmoma of the Naso-Pharynx. PMID- 20312228 TI - Pyloric Stenosis of Infancy. PMID- 20312227 TI - Tuberculosis of the Urinary System. PMID- 20312229 TI - A Case of Chronic Middle Ear Suppurations, Cholesteatoma, and Mastoiditis, complicated by Labyrinthitis, Sinus, Thrombosis and Meningitis. PMID- 20312230 TI - Treatment of Obstructive DysmenorrhOEA. PMID- 20312231 TI - Demonstration: Preparations Illustrating the Causes of the Tick Paralysis of British Columbia, Rocky Mountain Fever, Infective Jaundice and Yellow Fever. PMID- 20312232 TI - Renal Calculus. PMID- 20312233 TI - Some of the Severer Forms of Chronic Headaches. PMID- 20312234 TI - Cases of Ectopic Pregnancy. PMID- 20312235 TI - Chronic Intussusception with Polypus. PMID- 20312236 TI - A Case of Endothelioma of the Pleura with Multiple Metastasis. PMID- 20312237 TI - Aphasia in a left-handed Individual consequent upon a right Cerebral Lesion. PMID- 20312238 TI - An Unusual Case of Retro-Peritoneal Congenital Cyst probably arising from the Wolffian Body. PMID- 20312239 TI - Buried Chromic Catgut Sutures acting as Recurrent Abscesses Thirty Years after their Insertion. PMID- 20312240 TI - Scurvy. PMID- 20312242 TI - Influenza again Epidemic. PMID- 20312241 TI - Tabes Dorsalis with Gastric Manifestations. PMID- 20312243 TI - Surgery and "The Unknown Quantity". PMID- 20312244 TI - The Vancouver Meeting. PMID- 20312245 TI - History of the Events which led to the Passing of the British Anatomy Act, A.D. 1832. PMID- 20312246 TI - Progress Report upon Preparation of Material for Army Medical Department of Canadian War Museum. PMID- 20312247 TI - NEW FACTS, NEW SUGGESTIONS. PMID- 20312248 TI - Thoracoplasty for Chronic Chest Cavities. PMID- 20312249 TI - Peripheral Nerve Injuries. PMID- 20312251 TI - The Genesis, Classification, Interrelationships and Clinical Diagnosis of Disease. PMID- 20312250 TI - Obstetrics and the State. PMID- 20312252 TI - Headache of Nasal Pharyngeal and Aural Origin. PMID- 20312254 TI - Lessons from War Surgery. PMID- 20312253 TI - Report of Fifty-Eight Cases of delayed Arsenical Poisoning, following the Administration of "606" Preparations. PMID- 20312255 TI - Primary Sarcoma of the Mediastinum with Post Mortem. PMID- 20312257 TI - Submaxillary Salivary Calculus. PMID- 20312256 TI - Chronic Diarrhoea associated with an Adenoma of the Thyroid Gland. PMID- 20312258 TI - Erythema Multiforme mistaken for Lesions due to Chemical Poisoning. PMID- 20312260 TI - Prophylaxis of Influenza. PMID- 20312259 TI - Veil-pin in a Bronchus Removed through Bronchoscope. PMID- 20312261 TI - Salvarsan in Syphilis. PMID- 20312262 TI - Editorial Notes. PMID- 20312264 TI - Internal Hydrocephalus. PMID- 20312263 TI - Digitalis. PMID- 20312265 TI - The Ontario Medical Association Reorganization. PMID- 20312268 TI - Cancer of the Uterus with Special Reference to Diagnosis. PMID- 20312267 TI - Wounds and Infections of the Knee Joint. PMID- 20312266 TI - The Union of Septic Compound Fractures. PMID- 20312270 TI - Certain Bacteriological and Serological Aspects of Epidemic Influenza. PMID- 20312269 TI - The Causes of Death in Men who died from Gunshot Wounds of the Abdomen. PMID- 20312271 TI - On the early Diagnosis of Variola: A Note on the Conditions of the Blood and Spleen. PMID- 20312272 TI - Pulmonary Abscess following Extraction of the Teeth. Cure by Artificial Pneumothorax. PMID- 20312273 TI - Severe Purpura Haemorrhagica (Morbus Maculosus Werlhofii). Cured by Direct Transfusion. PMID- 20312275 TI - Notes from Radiographic Department. A New Method of confirming the Diagnosis of Cirrhosis of the Liver by Radiography. PMID- 20312274 TI - Chronic Parenchymatous Nephritis (Nephrosis) Illustraing the Results Obtained by Dietetic Treatment. PMID- 20312276 TI - Myocarditis with Sudden Death Illustrating the Significance of the Inverted T in the Electrocardiogram as a Grave Prognostic Sign. PMID- 20312277 TI - Late Results in a Case of Resection of Small Intestine for a Fibro-Sarcoma Associated with a Recurrent Melaena. PMID- 20312278 TI - Torsion of an Ovarian Cyst Complicating Pregnancy. PMID- 20312279 TI - Case of Spontaneous Haemorrhage from the Great Omentum. PMID- 20312281 TI - On the AEtiology of Chronic Arthritis. PMID- 20312280 TI - Cerebral Haemorrhage simulating Uraemia. PMID- 20312283 TI - Biography of Sir William Osler. PMID- 20312282 TI - Canadian Research into Industrial Hygiene. PMID- 20312284 TI - Obstructive Dysmenorrhoea. PMID- 20312286 TI - Phosphorus as a Therapeutic Agent. PMID- 20312285 TI - Medical Education in China. PMID- 20312287 TI - Sciatica from an Orthopaedic Standpoint. PMID- 20312288 TI - Traumatism of the Spleen. PMID- 20312289 TI - Syphilis and Gonorrhoea from the Public Health Point of View. PMID- 20312291 TI - Some X-ray Plates and their Significance. PMID- 20312290 TI - A Plea for the Sphincter Ani. PMID- 20312292 TI - The Summer's Experience with Infectious Diarrhoea. PMID- 20312294 TI - Medical Board Work on Psychiatric Cases. PMID- 20312293 TI - The need of Psychopathic Hospitals in Canada. PMID- 20312295 TI - Some Observations on the Occurrence of Acidosis after Anaesthesia. PMID- 20312296 TI - Prolongation of Life. PMID- 20312297 TI - Is there a Place for Spinal Analgesia. PMID- 20312298 TI - Torsion of the Left Testicle followed by Gangrene of the Testicle and Epididymis. PMID- 20312299 TI - Gangrene of the Caecum and Colon in a Case of Acute Dysentery. PMID- 20312300 TI - Influenza complicated by Incarcerated Fibroid Uterus and Missed Cervical Abortion. PMID- 20312301 TI - Advanced Training for Nurses. PMID- 20312302 TI - Surgery of the Peripheral Nerves. PMID- 20312304 TI - Resolution on the Death of Sir James Grant. PMID- 20312303 TI - Diuresis and the Caffein Group of Diuretics. PMID- 20312306 TI - Focal Infection. PMID- 20312305 TI - University of Toronto Extension Course in Paediatrics. PMID- 20312307 TI - The Present Day Treatment of Club Foot. PMID- 20312308 TI - Recent Studies of Scoliosis. PMID- 20312309 TI - The Work of a Psychopathic Hospital. PMID- 20312310 TI - Advances in Knowledge about the Blood-Cells during the past Six Years. PMID- 20312312 TI - Fibromyomata-Especial Reference to Radium Treatment. PMID- 20312311 TI - Medical Education. PMID- 20312314 TI - Heat and Infant Mortality. PMID- 20312313 TI - Incipient Diabetes Mellitus. PMID- 20312315 TI - Case 1. Fatal Haemorrhage from Duodenal Ulcer. PMID- 20312316 TI - Case 2. Fatal Haemorrhage from an Indolent Gastric Ulcer. PMID- 20312317 TI - Case 3. Intestinal Anastomosis for Chronic Toxaemia. PMID- 20312319 TI - Foreign Boby (Tartar) in the Right Lung, with Abscess of the Lung and Pyopneumothorax. PMID- 20312318 TI - Case 4. Carcinoma of the OEesophagus and Raynaud's Disease. PMID- 20312320 TI - Acute Phlegmonous Laryngitis, Streptococcus Septic Pneumonia. PMID- 20312321 TI - Abscess in a Patent Urachus in a Child Nine Months old. PMID- 20312322 TI - Pancreatitis, Experimental and Clinical. PMID- 20312323 TI - Pituitrin. PMID- 20312324 TI - Presidential Address. PMID- 20312325 TI - A Study of Epidemic Encephalitis based on the Study of Seventeen Cases with Two Autopsies. PMID- 20312326 TI - Recent Advances in Tendon Transplantation and Bone Grafting. PMID- 20312327 TI - Colostomy-a simple and inexpensive Contrivance to maintain perfect Cleanliness. PMID- 20312329 TI - Kala Azar. PMID- 20312328 TI - Functioning of the Heart in Cardiac Disease. PMID- 20312330 TI - The Anti-Tuberculosis Campaign A Social Campaign-the Role of the Government-the Role of Private Effort. PMID- 20312332 TI - Physical Examination of the Chest. PMID- 20312331 TI - A Paper on Shock. PMID- 20312333 TI - Water Supplies in Quebec. PMID- 20312334 TI - On the Taking and Examination of Throat Cultures. PMID- 20312335 TI - Bichloride of Mercury Poisoning by Vaginal Application. PMID- 20312336 TI - On the Causes and Definition of Cancer. PMID- 20312337 TI - Farewell Message from Major-General Fotheringham, C.M.G. PMID- 20312339 TI - The Nature and Treatment of Wound Shock and Allied Conditions. PMID- 20312338 TI - Arterial Hypertension. PMID- 20312340 TI - Certain Fundamental Errors in the Diagnosis and Treatment of Myocardial Insufficiency. PMID- 20312342 TI - Clinical Congress of the American College of Surgeons. PMID- 20312341 TI - The Surgical Treatment of Ulcerative Intestinal Tuberculosis as occurring chiefly in the course of Pulmonary Tuberculosis. PMID- 20312343 TI - Psychiatry and Internal Medicine. PMID- 20312344 TI - Acute Intestinal Obstruction with special reference to Diagnosis. PMID- 20312345 TI - The Importance of Biochemical Tests in Patients suffering from Prostatic Enlargement. PMID- 20312346 TI - Surgical Gynaecology. PMID- 20312347 TI - A Case of MyxOEdema. PMID- 20312348 TI - On the Changes in the Clinical Types of Infectious Disease. PMID- 20312349 TI - The Address in Surgery. PMID- 20312351 TI - The Alkaloidal Principles in Plants. PMID- 20312350 TI - The Address in Medicine. PMID- 20312352 TI - Subacute Infective Endocarditis. PMID- 20312353 TI - London as a Medical Centre: The British Fellowship of Medicine. PMID- 20312354 TI - Medicine and the War. PMID- 20312355 TI - A Plea for better Obstetrics. PMID- 20312356 TI - The Treatment of Haemorrhage in Medical Diseases. PMID- 20312357 TI - A Course of Treatment for Early Syphilis. PMID- 20312359 TI - The more Recent Developments in the Use of X-Rays in Commerce. PMID- 20312358 TI - Syphilis of the Central Nervous System; its early Recognition and Treatment. PMID- 20312360 TI - The Significance of the Calcium-Ion in the Cell-Experimental Tetany. PMID- 20312362 TI - The new Relationship between the State and the Practitioner in England. PMID- 20312361 TI - Report of the Treatment of a Case of Leukosarcoma with Mediastinal Involvement. PMID- 20312363 TI - Recent Advances in Pharmacology. PMID- 20312364 TI - Medical Education. PMID- 20312365 TI - The International Congress of Physiologists held at Paris, July, 1920. PMID- 20312367 TI - The Laboratory Diagnosis of Syphilis. PMID- 20312366 TI - A Consideration of the Thomson-Curtin Operation for Detached Retina with Report of Two Cases. PMID- 20312368 TI - Carcinoma of the Colon. PMID- 20312370 TI - A New View of the Induction of Immunity in the Enteric Diseases. PMID- 20312369 TI - Botulism-A Clinical Study of an Outbreak in the Yukon. PMID- 20312371 TI - Modern Views on the Care of Infectious Diseases. PMID- 20312372 TI - Radium for the State of New York. PMID- 20312373 TI - Goitre. PMID- 20312374 TI - Goitre and its Medical Treatment. PMID- 20312375 TI - Co-Relation of Results of Treatment by Surgical and X-Ray Methods. PMID- 20312376 TI - Myelogenous Leukaemia-Treatment by Benzol and X-Ray. PMID- 20312377 TI - The Diagnostic Value of the X-Ray Examination in Pulmonary Tuberculosis. PMID- 20312378 TI - A Further Study of Liver Atrophy by X-Ray Examination. PMID- 20312379 TI - Abscess of the Lung. PMID- 20312380 TI - Pulmonary Abscess. PMID- 20312381 TI - Surgical Tuberculosis. PMID- 20312382 TI - Treatment of Diabetes Mellitus. PMID- 20312383 TI - Further Report on the study of the Colon by the Opaque Enema-Summary of One Thousand Examinations. PMID- 20312384 TI - The Bleeding Uterus-Its Pathology, Diagnosis, and Treatment. PMID- 20312385 TI - A case of Secondary Keratitis. PMID- 20312386 TI - An Unusual Case of Epidemic Spinal Meningitis Complicated by an Intercurrent Attack of Measles. PMID- 20312387 TI - The Improved and Larger Journal. PMID- 20312388 TI - The Surgical Congress in Montreal. PMID- 20312389 TI - The Mace. PMID- 20312390 TI - Modern Views on Tuberculosis. PMID- 20312392 TI - Classified Bibliography of Sir William Osler's Canadian Period. PMID- 20312391 TI - Hudson's Bay Company Research Fellowship. PMID- 20312393 TI - BIOGRAPHY OF SIR WILLIAM OSLER. PMID- 20312394 TI - Biographical Sketch. PMID- 20312395 TI - Osler's Boyhood. PMID- 20312397 TI - Osler and the Montreal Veterinary College. PMID- 20312396 TI - Montreal Days. PMID- 20312398 TI - A Tribute to Sir William Osler. PMID- 20312400 TI - A Student's Impression of Osler. PMID- 20312399 TI - Early Days at the Johns Hopkins Hospital with Dr. Osler. PMID- 20312401 TI - Sir William Osler at Oxford. PMID- 20312402 TI - Sir William Osler and Oxford. PMID- 20312403 TI - Last Days of Sir William Osler. PMID- 20312404 TI - The Influence of William Osler on Medicine in America. PMID- 20312405 TI - Osler as Clinician and Teacher. PMID- 20312406 TI - Sir William Osler and the McGill Medical Library. PMID- 20312407 TI - Osler's Influence on the Research Student. PMID- 20312409 TI - FOREWORD. PMID- 20312408 TI - Memorial Sermon at Christ Church Cathedral. PMID- 20312410 TI - The Pathological Collections of the Late Sir William Osler and His Relations with the Medical Museum of McGill University. PMID- 20312411 TI - What's New. PMID- 20312412 TI - Canada's medical schools: Alberta and Laval. PMID- 20312413 TI - Renin in hypertension. PMID- 20312414 TI - Parasitic diseases. PMID- 20312415 TI - Minor opthalmology II. PMID- 20312417 TI - Respiratory tract infections in children. PMID- 20312416 TI - The Pickering Report, Part III: what the public thinks. PMID- 20312418 TI - Smallpox eradication. PMID- 20312419 TI - Limited licensure. PMID- 20312420 TI - The Pickering Report, Part IV: the social changes that confront today's physician. PMID- 20312421 TI - Canada's Medical Schools: UBC and Toronto. PMID- 20312422 TI - Canadian Labour Congress reaffirms position - "prepaying doctors' bills is not enough". PMID- 20312423 TI - [Not Available]. PMID- 20312424 TI - Abortion. PMID- 20312425 TI - Abortion. PMID- 20312426 TI - Abortion. PMID- 20312427 TI - Bilateral traumatic renal artery thrombosis. PMID- 20312428 TI - Nuchal infiltrations. PMID- 20312429 TI - Travel. PMID- 20312431 TI - Chinese medical journals resume publication. PMID- 20312430 TI - Basic research in acupuncture analgesia. PMID- 20312432 TI - Limb reimplantation complications and their management. PMID- 20312433 TI - A registered retirement savings plan such as CMARSP is best investment most doctors can make. PMID- 20312434 TI - Canada's medical schools: University of Ottawa and University of Calgary. PMID- 20312436 TI - Doctors on salary. PMID- 20312435 TI - Immunological aspects of autoimmune thyroiditis. PMID- 20312437 TI - Serum uric acid and coronary artery disease. PMID- 20312439 TI - [Not Available]. PMID- 20312438 TI - What does my association do for me? PMID- 20312440 TI - Government study names high tar, nicotine cigarettes. PMID- 20312441 TI - The Pickering Report, Part VI: earnings of doctors and review of fees. PMID- 20312442 TI - Suicide: public health and the silence of the heart. PMID- 20312443 TI - Limited licensure. PMID- 20312444 TI - Abortion and the pregnant teenager. PMID- 20312445 TI - The way I see it. PMID- 20312446 TI - The way I see it. PMID- 20312447 TI - "To see oursels as others see us!". PMID- 20312448 TI - Yersinia enterocolitica septicemia. PMID- 20312449 TI - Acute epiglottitis in adults. PMID- 20312450 TI - MD incomes 1961-71. PMID- 20312451 TI - Hypnosis and transplants. PMID- 20312453 TI - Hypnosis. PMID- 20312452 TI - Adjunctive management of a grossly unstable diabetic by hypnosis. PMID- 20312454 TI - The value of the mean corpuscular volume (MCV) as a screening test. PMID- 20312455 TI - Neurology review. PMID- 20312456 TI - The rare and the plentiful - a dilemma in pediatric manpower. PMID- 20312457 TI - Familial hypothalamic hypogonadotropic hypogonadism. AB - Clinical findings and endocrine studies are reported concerning six subjects (from two pedigrees) suffering from isolated hypogonadotropic hypogonadism. Their complete lack of any gonadotropin response to clomiphene stimulation, together with positive responses of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) to LH-releasing-hormone stimulation (LH-RH) provide evidence for a hypothalamic basis for this disorder. Additional data are presented indicating that variables such as circulating estrogen levels may influence the gonadotropin response to LH-RH. PMID- 20312458 TI - Psychomotor performance during insulin-induced hypoglycemia. AB - Subjects were given intravenous injections of insulin and/or saline on separate occasions and then tested on a pursuit-tracking task. Seven subjects showed clear clinical signs of hypoglycemia which were accompanied by a plasma glucose concentration of 32 mg/dl or less and by impaired tracking performance. Seven subjects showing no hypoglycemic signs despite insulin, and seven subjects receiving saline injections, showed no impairment in tracking. Impairment lasted from about the 15th to the 60th minute following injection, and was more readily apparent in response execution than response selection. There were no changes in accuracy of performance. Possible explanatory mechanisms, including neuroglycopenia, are discussed, and some implications for driving performance are noted. PMID- 20312459 TI - The evaluation of chronic psychiatric care. AB - During the past two decades the reduction in the size of the mental hospital population in this country has closely followed statistical predictions for bed requirements both in Canada and in the province of Ontario. The decrease has been most pronounced among chronic non-retarded patients. While these patients are now less evident in hospital statistics, it is suggested that improvements in their state may be more apparent than real, owing to differences in the terminology and numerators employed in presenting mental health statistics. Further, concern has been expressed about the quality of care received by former chronic patients now scattered through the community in a variety of after-care programs. Readmission rates have greatly increased in absolute terms and as a proportion of total admissions. The evaluation of the management of chronic psychiatric patients is discussed. PMID- 20312460 TI - Acute upper gastrointestinal tract bleeding and recent alcohol ingestion. AB - Alcohol ingestion is a reason for hospital admission for what may be termed trivial or even spurious gastrointestinal bleeding. This clinical entity can be recognized and hospital admission avoided. It is suggested that in the case of men under the age of 40 who present with a history of hematemesis and who are intoxicated to a variable degree but without a history of recent salicylate ingestion or previous dyspepsia, and in whom the hemoglobin level is above 13.0 g/dl it is acceptable management to send them home with instructions to seek help only if there is fresh, authenticated bleeding. This attitude is further supported by a normal blood volume measurement and the absence of blood from a gastric aspirate. PMID- 20312461 TI - Time and money in pediatric practice. AB - The types of services provided by pediatricians in Ontario and the payment they received from OHIP for a three-month period in 1972 are examined. Pediatricians provided 4.8% of the total of 16.3 million services and received 3.3% of the total $117.7 million payment. Most of the services were provided in ambulatory settings. Skin testing for allergy and hyposensitization accounted for 42% of the total of pediatric services. More than two thirds of pediatricians were engaged in provision of services which could be classified as primary care. Indeed, most of the services provided were of a primary care nature.There is a pressing need for redifining the pediatrician's role in our health-care delivery system and for a new look at his education. PMID- 20312462 TI - Constriction ring dystocia. AB - A case of constriction ring dystocia in a 40-year-old multiparous white woman is described. She was postmature; the fetus occupied an unstable lie for which no cause could be demonstrated clinically or radiologically; during the course of an inert labour every third fetal heart sound was abnormal. At cesarean section it appeared that no lower uterine segment had formed and extreme thickness of the myometrium was encountered. PMID- 20312463 TI - Pathophysiology of obesity. PMID- 20312464 TI - Anxiety states-experience with an automated group treatment. AB - Fifty patients drawn from a general practice were treated for manifest anxiety using relaxation techniques related to induction of hypnosis. The patients were instructed in groups of four to six with pretaped recordings.Forty-one patients completed the program which consisted of six one-hour recordings. Results indicated that 81% of those patients who subjectively evaluated their responses believed that they had been helped considerably. The impression gained from the study was that this method of treatment has useful application and that further study is warranted to assess more accurately the benefits of this approach to the psychotherapy of anxiety states. PMID- 20312465 TI - Health care insurance-U.S. style. PMID- 20312466 TI - MD Incomes 1961-71, Part II. PMID- 20312467 TI - Canada's Medical Schools: Dalhousie. PMID- 20312469 TI - Family problems in medical practice. PMID- 20312468 TI - Here's a last minute check for your income tax return that might save a few headaches. PMID- 20312470 TI - Health ministers reach agreement on broad variety of new measures. PMID- 20312471 TI - Comprehensive health insurance in U.S. - an idea whose time has come. PMID- 20312472 TI - An important recent decision: who's responsible for sponges used during an operation? PMID- 20312474 TI - China report. PMID- 20312473 TI - China report. PMID- 20312476 TI - Trendiness in the biomedical computer biz. PMID- 20312475 TI - Trendiness in the biomedical computer biz. PMID- 20312477 TI - What's New. PMID- 20312478 TI - Informedia will instruct and entertain waiting patients; could prove profitable investment for you. PMID- 20312479 TI - Disease costing claimed to be a tool to trim budgets but maintain quality. PMID- 20312480 TI - Dr. John stewart Henry. PMID- 20312481 TI - Perinatal intensive care. PMID- 20312482 TI - MD incomes 1961-71. PMID- 20312483 TI - Narcolepsy. PMID- 20312484 TI - Nonspecific humoral response associated with secondary syphilis. PMID- 20312485 TI - Drifting meridians. PMID- 20312486 TI - Drifting meridians. PMID- 20312487 TI - Winterwood. PMID- 20312489 TI - Saskatchewan adventure: a personal record. Part II, making contact. PMID- 20312488 TI - Life is real, life is earnest, next week and every week. PMID- 20312490 TI - They were first: six women medical pioneers. PMID- 20312491 TI - [Not Available]. PMID- 20312492 TI - [Not Available]. PMID- 20312493 TI - Age of consent: a warning for Ontario doctors. PMID- 20312494 TI - Nonprescription drugs to come under Food and Drugs Act. PMID- 20312495 TI - CMA position on nonprescription drugs. PMID- 20312496 TI - Fate of the chronic bronchitic. PMID- 20312497 TI - Reye's syndrome in a newborn. PMID- 20312498 TI - Hospital admission chest X-rays. PMID- 20312500 TI - Cervical cytology screening. PMID- 20312499 TI - Cervical cytology screening. PMID- 20312501 TI - Nocturnal enuresis. PMID- 20312502 TI - Birth control and abortion. PMID- 20312503 TI - The pickering report. PMID- 20312504 TI - Doctors on salary. PMID- 20312506 TI - Let practice experience provide input into research on health care system. PMID- 20312505 TI - Birth control and abortion. PMID- 20312507 TI - Hepatitis B antigen in screened blood units. PMID- 20312509 TI - Foulkes report in B.C. PMID- 20312508 TI - Hepatitis B antigen in screened blood units. PMID- 20312510 TI - Appreciation from an affiliate. PMID- 20312511 TI - A view from the hospital window. PMID- 20312512 TI - [Not Available]. PMID- 20312514 TI - WHO 1975 travel fellowships announced. PMID- 20312513 TI - American Lung Association residency fellowships available to Canadians. PMID- 20312516 TI - VD notifications continue to rise. PMID- 20312515 TI - [Not Available]. PMID- 20312517 TI - Canadian Mental Health Association seeks more protection for patients. PMID- 20312518 TI - McGill dean tells Montreal group to look for constructive ideas. PMID- 20312519 TI - Ontario's new Health Disciplines Act will put laymen on professional governing bodies. PMID- 20312521 TI - Old fluoroscopy machines. PMID- 20312520 TI - Funds available for research in birth defects. PMID- 20312522 TI - Witwatersrand graduates. PMID- 20312523 TI - Culture shock and the metric system: 28.5 ml of prevention may be worth 450 g of cure. PMID- 20312524 TI - [Not Available]. PMID- 20312525 TI - Canadian Medical Bonspiel has grandstand finish. PMID- 20312526 TI - [Not Available]. PMID- 20312527 TI - Transportation of sick neonates. PMID- 20312528 TI - Familial vitamin B(12) malabsorption. PMID- 20312529 TI - Survey of women physicians. PMID- 20312530 TI - Montreal GP appealing criminal negligence conviction in emergency patient death case. PMID- 20312531 TI - Acquired aphasia. PMID- 20312532 TI - Perinatal intensive care. PMID- 20312534 TI - Committees form base for health system: don't send a boy on a man's errand. PMID- 20312533 TI - Soviet-Canadian vignettes. PMID- 20312536 TI - [Not Available]. PMID- 20312535 TI - [Not Available]. PMID- 20312537 TI - [Not Available]. PMID- 20312538 TI - Nova Scotia's Tel-A-Pede provides advisory service in pediatrics for MDs. PMID- 20312539 TI - [Not Available]. PMID- 20312541 TI - Separation of health and welfare Canada. PMID- 20312540 TI - Onchocerciasis in Canada. PMID- 20312542 TI - Rigors following methicillin adminstration. PMID- 20312543 TI - Background papers for the Hastings Report. PMID- 20312544 TI - Background papers for the Hastings Report. PMID- 20312545 TI - Acute renal failure. PMID- 20312547 TI - Modern concepts about drowning. PMID- 20312546 TI - Metric misdemeanours. PMID- 20312548 TI - Metric conversion. PMID- 20312549 TI - Canadian council on hospital accreditation. PMID- 20312550 TI - [Not Available]. PMID- 20312551 TI - 'Stunted children not malnourished' - nutrition authority. PMID- 20312552 TI - Election puts two more doctors in the House. PMID- 20312553 TI - Dimensions of sports medicine. PMID- 20312555 TI - British medical profession takes stand against government rundown of health service. PMID- 20312554 TI - A study of a polemic. PMID- 20312557 TI - Suicide and depression in childhood and adolescence. PMID- 20312556 TI - Not every doctor is aloof and unavailable in a bureaucracy of waiting rooms. PMID- 20312558 TI - [Not Available]. PMID- 20312559 TI - Genetic research dangers worrying U.S. and Britain. PMID- 20312560 TI - McGill study to show if drivers with health problems more accident prone. PMID- 20312561 TI - Painful shoulder syndrome. PMID- 20312562 TI - Osler Medal essay contest 1975. PMID- 20312563 TI - Keeping pace - but out of step? PMID- 20312565 TI - Surgical privileges for retirement-age surgeons in a community hospital. PMID- 20312564 TI - Group practice: the way of the future? PMID- 20312566 TI - Doctors of music don't know the score. PMID- 20312568 TI - What's New. PMID- 20312567 TI - Salary versus fee-for-service: was Dr. Baltzan correct? PMID- 20312569 TI - Air pollution: disturbing new knowledge calls for major efforts in study and control. PMID- 20312570 TI - Of meetings. PMID- 20312571 TI - Drugs and faith healing. PMID- 20312572 TI - Quebec's Professional Code requires radical restructure of professional organization. PMID- 20312573 TI - The cure of folly. PMID- 20312574 TI - The non-system deserves a hand. PMID- 20312575 TI - Quebec government plans to do own hospital accreditation surveys. PMID- 20312576 TI - [Not Available]. PMID- 20312577 TI - Marijuana equals alcohol as road hazard, study shows. PMID- 20312578 TI - CMA policy on abortion. PMID- 20312579 TI - Screening for Tay-Sachs disease. PMID- 20312580 TI - CMA policy on abortion. PMID- 20312581 TI - CMA policy on abortion. PMID- 20312582 TI - Medical school enrolment. PMID- 20312583 TI - Asphyxiation due to choking. PMID- 20312584 TI - Verbum sapientibus. PMID- 20312585 TI - What's New. PMID- 20312586 TI - Rh sensitization following abortion. PMID- 20312587 TI - Doctors. PMID- 20312588 TI - Doctors. PMID- 20312589 TI - One small step for mankind. PMID- 20312590 TI - This book is worth study but it's annoying to read. PMID- 20312592 TI - The Cunnings report: two commentaries: ;Public has every right to details'. PMID- 20312591 TI - The Cunnings report: two commentaries: ;Report fails to address crucial issues'. PMID- 20312593 TI - A retirement of note. PMID- 20312594 TI - Painful shoulder syndrome. PMID- 20312595 TI - Hospital accreditation. PMID- 20312596 TI - Therapeutic abortion. PMID- 20312598 TI - Informing physicians about prescription drugs. PMID- 20312597 TI - The science of humane relations is one of the arts of the humanities. PMID- 20312599 TI - British medical deans and presidents issue unprecedented warning. PMID- 20312600 TI - Egalitarianism shaping doctors' lives. PMID- 20312601 TI - [Not Available]. PMID- 20312602 TI - [Not Available]. PMID- 20312603 TI - Economic council committee shifts emphasis to preventive health measures. PMID- 20312605 TI - Control of acupuncture seen as urgent by deputy ministers. PMID- 20312604 TI - Government finds $2.5 million extra medical research funds. PMID- 20312607 TI - [Not Available]. PMID- 20312606 TI - The budget means tax savings for you. PMID- 20312608 TI - ;Perspective' - proposal for potential policies not a prospect for pragmatists. PMID- 20312609 TI - [Not Available]. PMID- 20312610 TI - Cardiorespiratory fitness. PMID- 20312611 TI - Screening for hypertension. PMID- 20312613 TI - Composition of general council. PMID- 20312612 TI - Screening for hypertension. PMID- 20312615 TI - Acute rheumatic fever. PMID- 20312614 TI - Of meetings. PMID- 20312616 TI - Verbum sapientibus. PMID- 20312617 TI - Alternative to abortion. PMID- 20312618 TI - Unwanted pregnancies. PMID- 20312619 TI - The physician and Canadian law. PMID- 20312620 TI - Graduates of B.j. Medical college. PMID- 20312621 TI - [Not Available]. PMID- 20312622 TI - You don't have to go to Europe to find great skiing. PMID- 20312623 TI - What's New. PMID- 20312624 TI - To err is human,.. PMID- 20312625 TI - Wilful exposure to unwanted pregnancy. PMID- 20312626 TI - Medical school enrolment. PMID- 20312627 TI - Allergy and psychosis. PMID- 20312628 TI - The unwanted pregnancy. PMID- 20312629 TI - Medic-Alert bracelets. PMID- 20312630 TI - Some aspects of medical management of gastrointestinal disease. Part II. AB - Antacids are among the most frequently used drugs, yet common prescribing habits suggest that there is little familiarity with effective dosage schedules, side effects, or the differences between various antacid preparations. These factors, which are important in the choice of a specific antacid preparation, are discussed in an attempt to provide a rational basis for therapy.Corticosteroids, salicylazosulfapyridine (Salazopyrin) and diphenoxylate hydrochloride-atropine (Lomotil) are often used in treatment of inflammatory bowel disease. Recently described regimens for treating acute exacerbations and maintaining remission in patients with ulcerative colitis are reviewed, and attention is drawn to possible adverse effects of Lomotil in the treatment of colonic disease. PMID- 20312631 TI - What's New. PMID- 20312632 TI - Acute rheumatic fever. PMID- 20312634 TI - "We want to plug hop-skip-jump routine". PMID- 20312633 TI - Age of consent. PMID- 20312635 TI - ITC's ticket to paradise. PMID- 20312637 TI - Research by practising physicians. PMID- 20312636 TI - [Not Available]. PMID- 20312638 TI - This 'practical guide' is excellent; its study is urged. PMID- 20312639 TI - The irritable colon. PMID- 20312640 TI - [Not Available]. PMID- 20312641 TI - Infants and institutions. PMID- 20312642 TI - Wordsworth country: vales and hills and daffodils. PMID- 20312643 TI - The hyperactive child. PMID- 20312644 TI - Research in birth defects. PMID- 20312645 TI - Search for Bethune instruments. PMID- 20312646 TI - Clindamycin in human breast milk. PMID- 20312648 TI - BC interns and residents, salaried physicians in disputes. PMID- 20312647 TI - Northeast Canadian-American Health Seminar views problems of health care delivery. PMID- 20312649 TI - Flying some place? Sixty days forethought can save a pile of money. PMID- 20312650 TI - Treatment of hypothermia. PMID- 20312651 TI - Painful shoulder syndrome. PMID- 20312652 TI - The hyperactive child. PMID- 20312653 TI - The medical record. PMID- 20312654 TI - British doctors granted 30% pay hike in new NHS contract. PMID- 20312655 TI - The great trains of Europe an attractive proposition. PMID- 20312657 TI - [Not Available]. PMID- 20312656 TI - Self-inoculation with milk. PMID- 20312658 TI - Serum lipids in Canadian physicians. PMID- 20312659 TI - Food asphyxiation. PMID- 20312660 TI - Food asphyxiation. PMID- 20312661 TI - ECG changes during exercise. PMID- 20312662 TI - The new Cuba brings back the old Caribbean. PMID- 20312664 TI - Secondary osteomyelitis. PMID- 20312663 TI - [Not Available]. PMID- 20312665 TI - Solitary thyroid metastasis. PMID- 20312667 TI - Occupational medicine. PMID- 20312666 TI - Occupational medicine. PMID- 20312668 TI - Cost of primary care. PMID- 20312669 TI - Cost of primary care. PMID- 20312670 TI - Carbohydrates and brain metabolism. PMID- 20312671 TI - Health guide for travellers. PMID- 20312672 TI - How to save money on renting a car in Europe. PMID- 20312674 TI - A primary physician and his mentors. PMID- 20312673 TI - Error in drug dosage. PMID- 20312675 TI - Dogs and intestinal parasites. PMID- 20312676 TI - Stamps of Canadian medical interest. PMID- 20312677 TI - Agathanasia. PMID- 20312678 TI - The old home town's suffered progress but the squirrels are just the same. PMID- 20312680 TI - Independent consumer report says NHS hasn't standardized health care in Britain. PMID- 20312679 TI - First exam in UK for graduates of foreign medical schools fails 60%. PMID- 20312681 TI - Ontario government seeks physician support in seat belt campaign. PMID- 20312682 TI - Neoplastic disease in Eskimos. PMID- 20312683 TI - [Not Available]. PMID- 20312684 TI - Depression after myocardial infarction. PMID- 20312686 TI - SMA acts to preserve public confidence in anesthesia and medicine generally. PMID- 20312685 TI - The retrospective study: a Point of View. PMID- 20312687 TI - Good medical papers: whose responsibility? PMID- 20312688 TI - As others see us. PMID- 20312689 TI - Measure of a family doctor's work. PMID- 20312690 TI - Selection of medical students. PMID- 20312691 TI - US Congressmen learn of strengths, weaknesses of Canadian health care system. PMID- 20312692 TI - Slips that pass in the type. PMID- 20312693 TI - [Not Available]. PMID- 20312694 TI - Therapeutic abortion. PMID- 20312695 TI - Special report: CMA delegation at Parliamentary hearing offers view on income restraint. PMID- 20312696 TI - Computer tomography and diagnosis of CNS lesions. PMID- 20312697 TI - Ischemic heart disease and elements in water. PMID- 20312698 TI - Antibiotics in children. PMID- 20312699 TI - The Ulysses syndrome. PMID- 20312701 TI - Peace and medicine: is Christmas out of print? PMID- 20312700 TI - Chiropractic. PMID- 20312702 TI - Congenital absence of vas deferens. PMID- 20312704 TI - Snowstorm. PMID- 20312703 TI - International fellowship for advanced biomedical studies. PMID- 20312705 TI - Depression after myocardial infarction. PMID- 20312706 TI - Fomites in vaginitis. PMID- 20312707 TI - Fomites in vaginitis. PMID- 20312708 TI - Former tuberculosis patients and blood donors. PMID- 20312709 TI - Income tax deduction for severe respiratory disability. PMID- 20312711 TI - Cephradine in pediatric practice. PMID- 20312710 TI - Gonococcal vulvitis and vaginitis in children. PMID- 20312712 TI - Marriage, a slow death? PMID- 20312713 TI - Continuity of medical care. PMID- 20312714 TI - Victoria High School centennial celebrations. PMID- 20312715 TI - Report on prisoners of conscience. PMID- 20312716 TI - Canada's national sport. PMID- 20312718 TI - Drug abuse double-think. PMID- 20312717 TI - Insect-sting kits. PMID- 20312719 TI - Retinoic acid in acne therapy. PMID- 20312720 TI - Chiropractor in medical school. PMID- 20312722 TI - Vitamin D supplements. PMID- 20312721 TI - Particle size of radioisotope colloids. PMID- 20312723 TI - Recent library acquisitions. PMID- 20312724 TI - The hyperkinetic child. PMID- 20312725 TI - Reactions to insect bites. PMID- 20312726 TI - Mercenary physicians. PMID- 20312727 TI - Listing of investigational and emergency drugs. PMID- 20312728 TI - Addiction to research: a personal 25-year recollection. PMID- 20312729 TI - Outlawing the snowmobile. PMID- 20312730 TI - Interval between food and anesthesia - 5-hour rule. PMID- 20312731 TI - The causes and treatment of non-disease. PMID- 20312732 TI - Splashback and vaginitis. PMID- 20312733 TI - Seat belt legislation. PMID- 20312734 TI - CMARSP withdrawals. PMID- 20312735 TI - Australian medical benefit schedule 10 years ahead. PMID- 20312736 TI - Chiropractic: semantic problems. PMID- 20312738 TI - Estrogen and impotence. PMID- 20312737 TI - Investigation and treatment of allergic asthma. PMID- 20312739 TI - Estrogen and impotence. PMID- 20312740 TI - Anticipating the great changes to come in the era of SI. PMID- 20312741 TI - Self-induced water intoxication. PMID- 20312742 TI - Requests for medical records. PMID- 20312743 TI - Journal perspectives. PMID- 20312744 TI - Septic superficial thrombophlebitis: a major threat from a minor lesion. AB - Sites of insertion of peripheral intravenous catheters remain an important but often overlooked source of hospital-acquired septicemia and the most important source of staphylococcal septicemia. Septic superficial thrombophlebitis is characterized by severe local pain and is readily evident clinically. Care of the intravenous line can prevent this complication. To be diagnosed, it must be suspected. Treatment consists of removal of the intravenous line and administration of heparin and antibiotics effective against penicillinase producing organisms. Occasionally the vein must be ligated or, preferably, removed. PMID- 20312745 TI - Shrink. PMID- 20312746 TI - Dysponesis within the body politic. PMID- 20312747 TI - Treatment of acute leukemia in children. PMID- 20312748 TI - Pediatric emergency services of the future. PMID- 20312749 TI - Physician referral patterns: study needed. PMID- 20312750 TI - The great imitator. PMID- 20312751 TI - "Rendering account". PMID- 20312752 TI - Wasted research. PMID- 20312753 TI - Shady practice. PMID- 20312755 TI - Bromide intoxication. PMID- 20312754 TI - OCATH removal of intern and resident authority. PMID- 20312756 TI - The Dublin meeting. PMID- 20312757 TI - The Irish experience. PMID- 20312758 TI - A classification for family medicine. PMID- 20312759 TI - Long-term psychiatric care. PMID- 20312760 TI - Long-term psychiatric care. PMID- 20312761 TI - Long-term psychiatric care. PMID- 20312762 TI - Anatomical musings. PMID- 20312764 TI - Student selection and internship: fear oft accompanies shaking of traditional beliefs. PMID- 20312763 TI - OHIP mystery. PMID- 20312765 TI - Northern health care. PMID- 20312767 TI - Pride or prejudice? PMID- 20312766 TI - The Canadian abortion law. PMID- 20312768 TI - Care of the mentally ill. PMID- 20312769 TI - Care of the mentally ill. PMID- 20312770 TI - Cholera in Canada. PMID- 20312772 TI - The canadian home fitness test. PMID- 20312771 TI - The canadian home fitness test. PMID- 20312773 TI - Locked wards in Canadian mental hospitals. PMID- 20312774 TI - The 5-hour rule. PMID- 20312775 TI - Medical education: edifice or edification. PMID- 20312776 TI - Inequity in current library regulations. PMID- 20312778 TI - Severe variable decelerations in fetal heart rate. PMID- 20312777 TI - Medical education: edifice or edification. PMID- 20312779 TI - Diabetic day-care unit. PMID- 20312781 TI - Allergy to chocolate. PMID- 20312780 TI - Investigation and treatment of allergic asthma. PMID- 20312782 TI - Transcendental meditation. PMID- 20312783 TI - Transcendental meditation. PMID- 20312784 TI - Measurement of blood pressure. PMID- 20312785 TI - Saskatchewan's time limit on medicare claims. PMID- 20312787 TI - The stress concept. PMID- 20312786 TI - The journal. PMID- 20312788 TI - Premature labour. PMID- 20312789 TI - Premature labour. PMID- 20312790 TI - Anencephaly associated with megavitamin therapy. PMID- 20312791 TI - Anencephaly associated with megavitamin therapy. PMID- 20312793 TI - Carcinoma cocktail. PMID- 20312792 TI - Cervical cancer screening programs. PMID- 20312794 TI - Textbook of orthopaedic medicine. PMID- 20312795 TI - Textbook of orthopaedic medicine. PMID- 20312796 TI - Herpes vulvitis. PMID- 20312797 TI - Bromide intoxication. PMID- 20312799 TI - Nontartrazine-containing drugs. PMID- 20312798 TI - Bromide intoxication. PMID- 20312800 TI - An apology. PMID- 20312801 TI - Inequity in current library regulations. PMID- 20312802 TI - Gentamicin in ventilation apparatus. PMID- 20312803 TI - Health manpower statistics. PMID- 20312804 TI - Physician manpower requirements. PMID- 20312805 TI - Emotional "unhealth". PMID- 20312806 TI - Cervical cancer screening program. PMID- 20312807 TI - Laboratory investigation of cholera. PMID- 20312808 TI - Incorrect figure cited. PMID- 20312809 TI - An alert to genital actinomycosis. PMID- 20312811 TI - Medical roles. PMID- 20312810 TI - Cholera in Canada. PMID- 20312812 TI - Clinical application of triiodothyronine measurement. PMID- 20312813 TI - Clinical application of triiodothyronine measurement. PMID- 20312814 TI - Colic and urinary tract infection. PMID- 20312815 TI - Injury from ingested glass particles. PMID- 20312816 TI - CMA committee report on Connaught Laboratories Ltd. AB - Highlights of a report made by the Canadian Medical Association appointed committee on Connaught Laboratories Ltd. include a historical perspective and a description of the institution's present corporate setting.A sample of criticisms of interest to practising physicians is presented. The committee concludes that it is essential for Canada to be self-sufficient in the manufacture of necessary biologicals and that Connaught Laboratories Ltd. could serve such a function provided there is, inter alia:* A clear commitment by the Canada Development Corporation and the federal government to provide necessary support;A new president quickly appointed, capable of understanding the nature of the industry;* Adequate support for research;* Recruitment of new staff;* Renewal and renovation of facilities where necessary; and* Improved internal organization and communication. PMID- 20312817 TI - Corticosteroids prescribed in Mexicali. PMID- 20312818 TI - Molluscum contagiosum. PMID- 20312820 TI - Close loopholes, not doors. PMID- 20312819 TI - Scientific and medical journals. PMID- 20312822 TI - Prenatal diagnosis of genetic disease. PMID- 20312821 TI - Prenatal diagnosis of genetic disease. PMID- 20312823 TI - Tartrazine-containing drugs. PMID- 20312824 TI - The Canadian abortion law. PMID- 20312826 TI - The Canadian abortion law. PMID- 20312825 TI - The Canadian abortion law. PMID- 20312828 TI - The Canadian abortion law. PMID- 20312827 TI - The Canadian abortion law. PMID- 20312829 TI - The Canadian abortion law. PMID- 20312830 TI - Transcendental meditation. PMID- 20312831 TI - Pleomorphic carcinoma of the thyroid. PMID- 20312832 TI - Needed: alternative to the Compendium of Pharmaceuticals and Specialties. PMID- 20312833 TI - Waiting years. PMID- 20312834 TI - Canadian home fitness test. PMID- 20312835 TI - Metabolism of ethanol in different racial groups. PMID- 20312836 TI - Pellagra. PMID- 20312837 TI - Life devoid of value? PMID- 20312839 TI - British legislation affecting returning physicians. PMID- 20312838 TI - Treatment for travelling athletes. PMID- 20312840 TI - Warfare denied. PMID- 20312841 TI - Multiple myeloma and low back pain. PMID- 20312842 TI - Delay in delivery of the Journal. PMID- 20312843 TI - Tribute to a.d. Kelly. PMID- 20312844 TI - Bill C-37: a commentary. PMID- 20312845 TI - Poliomyelitis resurfaced: another view. PMID- 20312846 TI - Abortion-a positive experience? PMID- 20312847 TI - Percutaneous radiofrequency lumbar rhizolysis. PMID- 20312848 TI - Several possible approaches to audit. PMID- 20312849 TI - Antimicrobial drug use in hospitals. PMID- 20312850 TI - Antimicrobial drug use in hospitals. PMID- 20312851 TI - Grand multiparity - a continuing threat: a 6-year review. AB - Review of pregnancy and labour in 1005 grand multiparas who delivered during the 6-year period 1968 to 1973 disclosed an increase in frequency of many of the complications of pregnancy, particularly antepartum hemorrhage, hypertensive disorders and malpresentations. Almost one quarter of the patients received little or no antenatal care. The incidence of low birth-weight and stillbirth was significantly higher in the infants of the patients who had received no antenatal care. Comparison with the total hospital population showed that the perinatal mortality was almost doubled and the maternal mortality was increased 10-fold. The findings suggest that in modern obstetric practice the grand multipara continues to be a high-risk patient from both a maternal and fetal standpoint and that this has important clinical implications. PMID- 20312853 TI - Hazards of blood collection. PMID- 20312852 TI - Pharmaceutical Advertising Advisory Board and advertising in the Journal. PMID- 20312854 TI - The compendium of pharmaceuticals and specialties. PMID- 20312856 TI - The compendium of pharmaceuticals and specialties. PMID- 20312855 TI - Continuing medical education. PMID- 20312857 TI - Health care evaluation seminar. PMID- 20312858 TI - Traumatic vasospastic disease in chain-saw operators. PMID- 20312859 TI - Follow-up after treatment of gonococcal urethritis. PMID- 20312860 TI - Follow-up after treatment of gonococcal urethritis. PMID- 20312861 TI - Chemical detection of pheochromocytoma. PMID- 20312862 TI - Technetium pyrophosphate scanning in acute myocardial infarction. PMID- 20312863 TI - Tribute to a.d. Kelly. PMID- 20312864 TI - Things might not work out in the end. PMID- 20312865 TI - More vignettes of war. PMID- 20312866 TI - Low back pain in workmen. PMID- 20312868 TI - Living with the dying. PMID- 20312867 TI - Rational and irrational use of antibiotics. PMID- 20312869 TI - Hemophilia registration. PMID- 20312871 TI - Leaders haven't learned lessons of history. PMID- 20312870 TI - Correct use of aerosol inhalers. PMID- 20312872 TI - Learning to write well. PMID- 20312873 TI - Mammography and xerography. PMID- 20312875 TI - The Family practice nurse. PMID- 20312874 TI - Complication of jejunoileal shunt. PMID- 20312876 TI - The Family practice nurse. PMID- 20312878 TI - Inconsistencies in therapeutic abortion report. PMID- 20312877 TI - The Family practice nurse. PMID- 20312879 TI - Canadian critical care society. PMID- 20312880 TI - Intestinal infarction in women taking oral contraceptives. PMID- 20312881 TI - Adverse reactions to 1975 bivalent influenza vaccine in children. PMID- 20312882 TI - Intestinal infarction in women taking oral contraceptives. PMID- 20312883 TI - Dosage, compliance and bioavailability in perspective. PMID- 20312884 TI - Intestinal infarction in women taking oral contraceptives. PMID- 20312885 TI - Intestinal infarction in women taking oral contraceptives. PMID- 20312886 TI - Office diagnosis of breast cancer. PMID- 20312887 TI - Office diagnosis of breast cancer. PMID- 20312888 TI - Measurement of nitrous oxide concentrations in operating-room air. PMID- 20312889 TI - Measurement of nitrous oxide concentrations in operating-room air. PMID- 20312890 TI - Medicolegal role in tests. PMID- 20312891 TI - [Not Available]. PMID- 20312892 TI - Poisoning by drug overdose. PMID- 20312893 TI - Student selection for medical school. PMID- 20312894 TI - Symposium on diarrhea. PMID- 20312895 TI - Symposium on diarrhea. PMID- 20312896 TI - Allergy testing. PMID- 20312897 TI - Police and the law. PMID- 20312898 TI - Police and the law. PMID- 20312899 TI - Biting insect summary. PMID- 20312900 TI - Dr. D.a.e. Shephard. PMID- 20312901 TI - The saccharin ban. PMID- 20312902 TI - The saccharin ban. PMID- 20312903 TI - What can YOU do about health care costs? PMID- 20312904 TI - The cost of cigarettes as compared with physicians' services. PMID- 20312905 TI - Contraception counselling and therapeutic abortion. PMID- 20312906 TI - Physicians' help requested. PMID- 20312907 TI - Screening for urinary tract infection. PMID- 20312908 TI - Diphtheria in quebec. PMID- 20312909 TI - Communicating with patients. PMID- 20312911 TI - Screening for urinary tract infection. PMID- 20312912 TI - Routine immunization schedules, Health and Welfare Canada advisory committee on immunizing agents. PMID- 20312910 TI - Derivatives of 8-hydroxyquinoline and neurologic damage. PMID- 20312913 TI - Congenital deformities associated with Bendectin. PMID- 20312914 TI - Inflation and the medical profession. PMID- 20312915 TI - Evaluating disulfiram implantation. PMID- 20312917 TI - Evidence and belief. PMID- 20312916 TI - Prostaglandins and the ductus arteriosus. PMID- 20312918 TI - History, science and the community. PMID- 20312919 TI - Student selection for medical school. PMID- 20312920 TI - Student selection for medical school. PMID- 20312921 TI - Musings on personal life. PMID- 20312922 TI - Prophylaxis for exposure to rabies in humans. PMID- 20312923 TI - Musings on personal life. PMID- 20312924 TI - Resuscitation from cardiac arrest during accidental hypothermia. PMID- 20312925 TI - The Trojan computer. PMID- 20312926 TI - What do family physicians see in practice? PMID- 20312927 TI - Is gynecology good for obstetrics? PMID- 20312928 TI - What do family physicians see in practice? PMID- 20312929 TI - Communicating with patients. PMID- 20312930 TI - Anderson report on anesthesia. PMID- 20312931 TI - Suicide and attempted suicide among the aged. PMID- 20312932 TI - What do family physicians see in practice? PMID- 20312933 TI - Evaluation of the Canadian Home Fitness Test in middle-aged men. PMID- 20312934 TI - University of Ottawa graduates. PMID- 20312935 TI - Stocking stuffers. PMID- 20312936 TI - Suicide and attempted suicide among the aged. PMID- 20312937 TI - What do family physicians see in practice? PMID- 20312938 TI - Research or marketing survey? PMID- 20312939 TI - Consent to medical treatment. PMID- 20312940 TI - Pilot study of high-protein, high-vitamin, low-carbohydrate, sugar-free diet in learning-disabled children. PMID- 20312941 TI - Treatment of obesity by exercise in the cold. PMID- 20312942 TI - Unsolicited advertising. PMID- 20312943 TI - Diphtheria in quebec. PMID- 20312944 TI - Acute lindane poisoning. PMID- 20312945 TI - Urinary homovanillic acid, dopamine and norepinephrine excretion in patients with essential hypertension. PMID- 20312946 TI - The Trojan computer. PMID- 20312947 TI - Prognosis in anorexia nervosa. PMID- 20312948 TI - Living with the dying. PMID- 20312950 TI - Aneroid sphygmomanometers. PMID- 20312949 TI - Blood group B and Neisseria gonorrhoeae antigens. PMID- 20312951 TI - Life is a mutual affair. PMID- 20312952 TI - Code of marketing practice. PMID- 20312953 TI - Radical radiotherapy versus abdominoperineal resection. PMID- 20312954 TI - Optometrists. PMID- 20312955 TI - Present status of breast cancer screening. PMID- 20312956 TI - Radical radiotherapy for rectal cancer. PMID- 20312957 TI - Physicians on the move. PMID- 20312958 TI - Treatment of accidental hypothermia with peritoneal dialysis. PMID- 20312959 TI - The canadian home fitness test. PMID- 20312960 TI - Protein-energy malnutrition. PMID- 20312961 TI - Hydrogen sulfide poisoning. PMID- 20312962 TI - Hydrogen sulfide poisoning. PMID- 20312963 TI - Low hemoglobin values in athletes. PMID- 20312964 TI - Code of Ethics: abortion referral. PMID- 20312965 TI - Code of Ethics: abortion referral. PMID- 20312966 TI - Code of Ethics: abortion referral. PMID- 20312968 TI - Code of Ethics: abortion referral. PMID- 20312967 TI - Code of Ethics: abortion referral. PMID- 20312969 TI - Code of Ethics: abortion referral. PMID- 20312970 TI - Fetal mortality 100%. PMID- 20312971 TI - Severe vaccine reaction. PMID- 20312972 TI - Normal-pressure hydrocephalus. PMID- 20312973 TI - Sir andrew macphail. PMID- 20312974 TI - Rebuttal by brantford clinic. PMID- 20312975 TI - Canadians for Health Research conference. PMID- 20312976 TI - Eye injuries in squash. PMID- 20312977 TI - Eye injuries in squash. PMID- 20312978 TI - Festive dachshunds. PMID- 20312979 TI - Molecular manipulation. PMID- 20312980 TI - Industrial hygiene programs. PMID- 20312981 TI - Lassa Fever. PMID- 20312982 TI - Child custody cases: the role of the psychiatrist. PMID- 20312983 TI - Influence of aortocoronary bypass surgery on employment. PMID- 20312984 TI - Misuse of statistical terminology. PMID- 20312985 TI - Electroconvulsive therapy today. PMID- 20312986 TI - Electroconvulsive therapy today. PMID- 20312987 TI - Square pegs in round holes. PMID- 20312988 TI - Square pegs in round holes. PMID- 20312989 TI - [Not Available]. PMID- 20312990 TI - Prognosis for survival in neonatal meningitis. PMID- 20312991 TI - Prognosis for survival in neonatal meningitis. PMID- 20312992 TI - Views on ageing. PMID- 20312993 TI - Prevention or cure? PMID- 20312994 TI - Coroner's office unaware of questionable deaths. PMID- 20312995 TI - Convoluted english. PMID- 20312996 TI - Accidents in endotracheal intubation. PMID- 20312997 TI - The controversial internship. PMID- 20312998 TI - The interview. PMID- 20312999 TI - The controversial internship. PMID- 20313000 TI - Gonococcal arthritis in pregnancy. PMID- 20313001 TI - Signing of absentee medical certificates by physicians. PMID- 20313002 TI - Relief of pain by infiltration of autonomic ganglia with steroids. PMID- 20313003 TI - Physician-chiropractors. PMID- 20313004 TI - Treatment of obesity by cold exposure. PMID- 20313005 TI - Treatment of urinary tract infection with a single dose of trimethoprim sulfamethoxazole. PMID- 20313006 TI - The controversial internship. PMID- 20313007 TI - The sauna. PMID- 20313008 TI - Ethics and abortion referral. PMID- 20313009 TI - Zeroid: alternative treatment of hemorrhoids. PMID- 20313010 TI - Treatment by manipulation. PMID- 20313011 TI - The need for Campylobacter subspecies identification. PMID- 20313012 TI - Viral pandemics originating from outer space? PMID- 20313013 TI - Amnesty International medical group. PMID- 20313014 TI - Ophthalmologists need support. PMID- 20313015 TI - The danger in food safety policies. PMID- 20313016 TI - Informed consent. PMID- 20313017 TI - Combination antibiotic therapy in prosthetic endocarditis due to Staphylococcus epidermidis. PMID- 20313018 TI - The controversial internship. PMID- 20313019 TI - The Heimlich maneuver. PMID- 20313020 TI - Cervicofacial emphysema. PMID- 20313021 TI - Code of ethics. PMID- 20313022 TI - The Controversial internship. PMID- 20313023 TI - The cult member as a patient. PMID- 20313024 TI - Retinoic acid in acne therapy. PMID- 20313025 TI - Directing the medical dollar. PMID- 20313026 TI - Medicine and contemporary cultism. PMID- 20313027 TI - Code of ethics. PMID- 20313028 TI - The wondering, wandering patient. PMID- 20313030 TI - Advertising breast feeding. PMID- 20313029 TI - Return to the art of medicine. PMID- 20313031 TI - Inappropriate placing of advertisement in Journal. PMID- 20313032 TI - Industrial health hazards. PMID- 20313033 TI - Hypertrophic osteoarthropathy in the presence of an abdominal aortic prosthesis. PMID- 20313034 TI - Safety of topical chloramphenicol in the treatment of acne vulgaris. PMID- 20313035 TI - Kit for "crossroaders". PMID- 20313036 TI - Views on ageing. PMID- 20313037 TI - "Dear health care provider...". PMID- 20313039 TI - Erroneous orthography. PMID- 20313038 TI - "Dear health care provider...". PMID- 20313040 TI - Infectious disbelief. PMID- 20313042 TI - Rediscovery of breast feeding. PMID- 20313041 TI - Adverse biochemical and clinical consequences of furosemide administration. PMID- 20313043 TI - Best wishes to ENT. PMID- 20313044 TI - Let's keep Christmas. PMID- 20313046 TI - Journal's style of capitalization. PMID- 20313045 TI - Mortality for cancer of the corpus uteri. PMID- 20313047 TI - Compliment to the journal. PMID- 20313049 TI - Foreword. PMID- 20313048 TI - Mistaken impression corrected. PMID- 20313050 TI - The Diagnosis of Gastric Ulcer. PMID- 20313051 TI - Duodenal Ulcer. PMID- 20313053 TI - Interim Report of Reorganization Committee. PMID- 20313052 TI - The Diagnosis of Gastric Ulcer. PMID- 20313054 TI - The Differential Diagnosis of Appendicitis. PMID- 20313056 TI - The Ontario Medical Association Enters into Active Participation in the Journal of the Canadian Medical Association. PMID- 20313055 TI - Some Unusual Abdominal Emergencies. PMID- 20313057 TI - Notes on Drainage in Surgery. PMID- 20313058 TI - The Practical Value of a Metabolism Clinic. PMID- 20313059 TI - The Present Day Conception of Hay Fever. PMID- 20313060 TI - The Reorganization of the Journal of the Canadian Medical Association. PMID- 20313061 TI - Two Cases of Pellagra in Canada. PMID- 20313062 TI - Focal Infection with Special Reference to Medical Inspection of Schools. PMID- 20313063 TI - Suture of Circumflex Nerve. PMID- 20313064 TI - The Relation of Physical Exhaustion to Chronic Ill-Health. PMID- 20313065 TI - An Interpretation of some Gastro-Intestinal Symptoms. PMID- 20313066 TI - Two Fatal Cases of Chronic Nephritis. PMID- 20313067 TI - Hospital Clinic on Syphilis of the Nervous System with a Case of Tabes Dorsalis. PMID- 20313068 TI - The Liability of the Medical Profession in the Commitment of the Supposedly Insane. PMID- 20313069 TI - Remarks on Some Gastro-Intestinal Problems. PMID- 20313070 TI - On the Use of Local Anaesthesia in Operations on the Upper Air Passages. PMID- 20313071 TI - Rehabilitative Work Carried on by the Rockefeller Foundation in Connection with the Medical Schools in Central Europe. PMID- 20313072 TI - Recent Studies in Problems Connected with Lactation and Infant Feeding. PMID- 20313073 TI - The Treatment of Diffuse Suppurative Peritonitis. PMID- 20313074 TI - Diverticulitis of the Large Bowel. PMID- 20313075 TI - The Treacherous Symptoms Caused by an Appendix in the Pelvis. PMID- 20313076 TI - Bright's Disease in Practice. PMID- 20313077 TI - OEsophageal Strictures. PMID- 20313078 TI - The Prevalence of Malnutrition in the Public School Children of Toronto. PMID- 20313080 TI - Observations from the Dermatological Clinic of the Department of Soldiers' Civil Re-Establishment of Canada, Toronto Branch. PMID- 20313079 TI - Diphtheritic Ulceration of the Skin. PMID- 20313081 TI - Primary and Secondary Nitrous Oxide Saturation for Relaxation and as a Test of the Patient's Capacity for Operation. PMID- 20313083 TI - The Development of Neurological Surgery. PMID- 20313082 TI - An Unusual Abdominal Condition Complicating Hour-Glass Stomach. PMID- 20313084 TI - The Acute Abdomen. PMID- 20313085 TI - Newer Ideas in the Treatment of Diabetes Mellitus. PMID- 20313086 TI - Dictionary of Altitudes in Canada. PMID- 20313087 TI - The AEtiology and Prophylaxis of Simple Goitre. PMID- 20313088 TI - On the Treatment of Acute Empyema. PMID- 20313089 TI - The Traumatic Abdomen. PMID- 20313090 TI - The Acute Abdomen Following Abdominal Operation. PMID- 20313091 TI - The Prognostic Value of the Study of the Blood Chemistry in the Acute Abdomen: Preliminary Report. PMID- 20313092 TI - Toxaemias of Pregnancy-Early Recognition and Treatment. PMID- 20313093 TI - The Epidemiology and Diagnosis of Encephalitis Lethargica. PMID- 20313095 TI - Notes on Footwear. PMID- 20313094 TI - Blood Transfusion. PMID- 20313096 TI - Surgical Clinic of Dr. F. N. G. Starr, Toronto General Hospital-Report of Two Cases of Pancreatitis. PMID- 20313097 TI - Continuous Fever in Children with Streptococcic Infection in the Blood Stream, with Recovery: Case Reports. PMID- 20313098 TI - Some Aspects of Fibro-Plastic Tuberculosis in the Eye. PMID- 20313100 TI - Notes on Epilepsy. PMID- 20313099 TI - Recurrent Dislocation of the Shoulder Joint. PMID- 20313101 TI - A Plea for the More General Use of Local Anaesthesia. PMID- 20313102 TI - Note on Seasonal Hay Fever. PMID- 20313103 TI - Hyperthyroidism-Present Status of Diagnosis and Treatment. PMID- 20313104 TI - Vitamines or Accessory Food Factors. PMID- 20313105 TI - The Value of an Estimation of the Urea Content of the Blood. PMID- 20313106 TI - The Association. PMID- 20313107 TI - INCOME TAX RETURNS. PMID- 20313108 TI - THE ADMINISTRATION OF ARSENICAL PREPARATIONS FOR THE TREATMENT OF SYPHILIS. PMID- 20313110 TI - The Art of Medicine. PMID- 20313109 TI - The Determination of Basal Metabolism by Estimation of the Respiratory Exchange (Indirect Calorimetry) as a Clinical Method in the Diagnosis and Treatment of Hyperthyroid and Hypothyroid States. PMID- 20313111 TI - A Resume of Diabetes Mellitus. PMID- 20313113 TI - Value of Fluroscopy in the Diagnosis of Abdominal Conditions. PMID- 20313112 TI - Diverticula of the Urinary Bladder. PMID- 20313114 TI - Intestinal Obstruction from Gall Stones. PMID- 20313116 TI - A Discussion of Case Reports Illustrating Some Anomalies in the Treatment of Gastric and Duodenal Ulcer. PMID- 20313115 TI - Surgical Clinic of Dr. F. N. G. Starr, Toronto General Hospital: Two Cases of Carcinoma of the Stomach. PMID- 20313117 TI - Case of Luetic Cirrhosis of the Liver, Successfully Treated by Anti-Syphilitic Measures and Repeated Tappings. PMID- 20313118 TI - Malignant Disease of the Lungs, Secondary to Carcinoma of the Prostate. Patient in Fair Health for Months. PMID- 20313119 TI - Advances in the Treatment of Hyperthyroidism. PMID- 20313120 TI - Thoughts on Problems Arising in Connection with the Treatment of the Insane. PMID- 20313121 TI - Hydrocephalus. PMID- 20313122 TI - Peccavimus. PMID- 20313123 TI - The Acute Abdomen. PMID- 20313124 TI - The Financing of Public Hospitals. PMID- 20313126 TI - Report on the Schick Test and Toxin-Antitoxin Immunization at the Children's Home, Winnipeg. PMID- 20313125 TI - Prognosis of Pulmonary Tuberculosis. PMID- 20313127 TI - The Prognostic Value of the Study of the Blood Creatinine in Nephritis: Based upon the Study of Fourteen Cases with Complete Post-mortem Examination. PMID- 20313128 TI - Some Unfortunate Sequelae of Suprapubic Prostatectomy. PMID- 20313129 TI - Notes on Night Blindness at the Front. PMID- 20313130 TI - The Physiology and Pharmacology of the Mammary Glands. PMID- 20313131 TI - A Review of Thirty-Three Cases of Foreign Bodies in the OEsophagus, Bronchi and Larynx. PMID- 20313132 TI - Diseases of Ethmoidal and Sphenoidal Sinuses. PMID- 20313133 TI - Non-Union Following Fracture. PMID- 20313134 TI - An Analysis of Some Cases of Perforation of the Stomach and Duodenum. PMID- 20313135 TI - The Use of Pituitary Extract and Scopolamine-Morphine in Obstetrics. PMID- 20313136 TI - Benign Neoplasms of the Female Pelvis. PMID- 20313137 TI - A National Hospital Day. PMID- 20313139 TI - Early Diagnosis of Diphtheria. PMID- 20313138 TI - Group Diagnosis and Group Therapy. PMID- 20313141 TI - On Digitalis Therapy. PMID- 20313140 TI - Pituitary Extract and Scopolamine-Morphine in Obstetrics. PMID- 20313142 TI - The Association. PMID- 20313143 TI - Criticism of the Expression "Acute Abdomen". PMID- 20313144 TI - The Importance of Precise Anatomical Knowledge in the Surgery of the Peripheral Nerves. PMID- 20313145 TI - The Surgical Treatment of Chronic Infected Open Pneumothorax. PMID- 20313146 TI - Injuries of the Spine. PMID- 20313147 TI - Dental Infection and Internal Medicine. PMID- 20313148 TI - The Nature of Acidosis in Nephritis. PMID- 20313150 TI - Novocaine in Surgical Operations: A Clinical Report of 459 Operative Cases in which Novocaine was used as a Local Anaesthetic. PMID- 20313149 TI - Fragilitas Ossium. PMID- 20313152 TI - The Causation of the Psychoneuroses. PMID- 20313151 TI - Chronic Infections of the Nasal Accessory Sinuses with Toxic Absorption. PMID- 20313153 TI - Appendicitis-High Mortality in Perforated Cases. PMID- 20313154 TI - The Future Function of Modern Medicine. PMID- 20313156 TI - Some Results of Protective Inoculation against Epidemic Influenza. PMID- 20313155 TI - Two Rare Abnormalities Occurring in the Same Subject-Partial Absence of the Corpus Callosum-the Stomach situated entirely within the Thorax. PMID- 20313158 TI - Spontaneous Rupture of the Bladder in Parturition. PMID- 20313157 TI - The Treatment of Anaemia by Drugs. PMID- 20313159 TI - Post-Mortem Delivery. PMID- 20313161 TI - A Chance for Mentally Defective Children. PMID- 20313160 TI - The Administration of Arsphenamine. PMID- 20313162 TI - Num Peccavimus? "Acute Abdomen". PMID- 20313163 TI - A New Method of Applying Drugs to the Posterior Urethra. PMID- 20313164 TI - The AEtiology of Epidemic Influenza-A Critical Review. PMID- 20313165 TI - Medical Organizations in Ontario and the Present Necessity: Annual Address of the President of the Ontario Medical Association. PMID- 20313166 TI - Cardiac Irregularities. PMID- 20313167 TI - Epidermophyton Infection. PMID- 20313169 TI - Apologia. PMID- 20313168 TI - The Use of Living Sutures in Operative Surgery. PMID- 20313170 TI - The Diagnosis of Chronic Cholecystitis. PMID- 20313171 TI - Generalized Neurofibromatosis. PMID- 20313172 TI - Fragilitas Ossium. PMID- 20313173 TI - Multiple Polypi in the Stomach (Gastric Polypsis). PMID- 20313174 TI - A Simple Method for Determining the Approximate Degree of Acidosis in Diabetes Mellitus : The Titration of Organic Acids in Urine, Van Slyke & Palmer. PMID- 20313175 TI - The Bacteriology of Infectious Diarrhoea. PMID- 20313176 TI - Report of a Case of Thrombosis of the Aorta and Iliac Arteries following Pneumococcal Infection of the Umbilicus. PMID- 20313177 TI - Asthma- Its Relation to Focal Infections. PMID- 20313178 TI - Tumours of the Urinary Bladder, Diagnosis and Treatment. PMID- 20313179 TI - Prevention of Mental Breakdown. PMID- 20313180 TI - Latency in Syphilis. PMID- 20313182 TI - Acidosis. PMID- 20313181 TI - Cod-Liver Oil Without Phosphorus as Effective as Cod-Liver Oil with Phosphorus in Rickets and Tetany. PMID- 20313183 TI - The Repair of Bony Defects of the Cranium. PMID- 20313185 TI - Case No. 1. Cholelithiasis-Acute haemorrhagic pancreatitis-Volvulus of the small intestine. PMID- 20313184 TI - The Toxic Action of Arsphenamine and Neoarsphenamine. PMID- 20313186 TI - Case No. 2. Perforated gastric ulcer-closure and posterior gastro-enterostomy. PMID- 20313187 TI - The Reoganization of the Canadian Medical Association. PMID- 20313188 TI - Suggested Reforms in the Canadian Medical Association. PMID- 20313189 TI - The Value of Rural Medical Centres. PMID- 20313190 TI - Presidential Address. PMID- 20313191 TI - The Doctrine of the Prepared Soil: A Neglected Factor in Surgical Infections. PMID- 20313192 TI - Prenatal Negligence and Loss of Population. PMID- 20313193 TI - Danger Signs in Diseases of the Gastro-Intestinal Tract and Differential Tests. PMID- 20313194 TI - Rational Empiricism. PMID- 20313195 TI - Notes on Lobar Pneumonia in France. PMID- 20313196 TI - Sarcomatous Abdominal Testicle in a Hermaphrodite. PMID- 20313197 TI - Modern Medicine and the General Practitioner. PMID- 20313198 TI - Basal Metabolism as a Guide in the Surgical Treatment of Goitre with Hyperthyroidism. PMID- 20313199 TI - Function of an Infectious Disease Hospital. PMID- 20313200 TI - The Detection of Lamblia [Giardia] Intestinalis by Means of the Duodenal Tube. PMID- 20313201 TI - The Nature of X-Rays and Some of Their Applications. PMID- 20313202 TI - Unsuspected Syphilis of the Nervous System: Its Laboratory Diagnosis : In Three Parts: Part One. PMID- 20313203 TI - The Clinical Aspect of Sub-Acute Bacterial Endocarditis. PMID- 20313204 TI - Treatment of Carcinoma of the Anus and Rectum. PMID- 20313205 TI - Chronic Pain in the Right Iliac Fossa. PMID- 20313206 TI - The Treatment of the Psychoneuroses. PMID- 20313207 TI - On the Influence of a Diet with High Protein Content on the Kidney. PMID- 20313208 TI - The Effect of Massive Doses of Diuretin. PMID- 20313209 TI - The Address in Surgery. PMID- 20313210 TI - The Presidential Address. PMID- 20313211 TI - A New Outlook for Hospitals for the Treatment of Infectious Disease. PMID- 20313212 TI - Caution Regarding Pluri Glandular Therapeutics. PMID- 20313213 TI - The Employment of the Roentgen Ray for Destruction of Hypertrophied Tonsillar Tissue. PMID- 20313214 TI - Treatment of Pneumonia with Special Reference to the Use of Serum. PMID- 20313215 TI - Etiology of Renal Infections, with Special Reference to Urinary Stasis in Infections of the Renal Pelvis. PMID- 20313216 TI - Spinal Deformity as a Cause of Cardiac Hypertrophy and Dilatation. PMID- 20313217 TI - Ganglion of the Wrist Region with Report of Two Cases Showing Destructive Tendon Involvement. PMID- 20313218 TI - The Cause of the "Ammoniacal Diaper". PMID- 20313219 TI - Tuberculous Peritonitis. PMID- 20313220 TI - Intestinal Tuberculous Infection in Children. PMID- 20313221 TI - A Case of Woody Thyroiditis. PMID- 20313222 TI - Blood Transfusion in Severe Burns in Infants and Young Children: A Preliminary Report of the Treatment of the Toxic Shock by Blood Transfusion-with or without preceding exsanguination. PMID- 20313223 TI - Tables Relative to the Transfusion of Blood. PMID- 20313224 TI - Unsuspected Syphilis of the Nervous System: Its Laboratory Diagnosis: In Three Parts: Part II. PMID- 20313225 TI - Standardization of Certain Preparations of Digitalis. PMID- 20313226 TI - Research in Medicine. PMID- 20313227 TI - Encephalitis Lethargica. PMID- 20313228 TI - On the Cause and Treatment of Rickets. PMID- 20313230 TI - Basal Metabolism and Goitre. PMID- 20313229 TI - Three Unusual Abdominal Tumours. PMID- 20313231 TI - On the Diagnosis of Tuberculosis in Infancy. PMID- 20313232 TI - On the Value of Cinchophen and Neo-cinchophen and Novaspirin in Rheumatic Fever. PMID- 20313233 TI - Effect of Tobacco Smoking on the Nervous System. PMID- 20313234 TI - On the Value of Iron in Anaemias. PMID- 20313235 TI - Difference Between Rectal and Colon Injections. PMID- 20313236 TI - Recent Smallpox in Edmonton and Deductions Therefrom. PMID- 20313237 TI - The Abatement of Venereal Disease. PMID- 20313238 TI - The Eye as a Signal of Disease. PMID- 20313239 TI - The Value of Expert Anaesthesia to All Concerned. PMID- 20313240 TI - An Ambulatory Treatment for Chronic Ulcers of the Leg. PMID- 20313241 TI - Nitrous Oxide-Oxygen Analgesia and Anaesthesia in Obstetrics. PMID- 20313242 TI - Recent Progress of the Mental Hygiene Movement in Canada. PMID- 20313243 TI - Unsuspected Syphilis of the Nervous System: Its Laboratory Diagnosis: In Three Parts: Part III. PMID- 20313244 TI - A Case of Giardiasis (Lambliasis) Intestinalis. PMID- 20313246 TI - The Treatment of Irreparable Nerve Injuries. PMID- 20313245 TI - Considerations Regarding the Surgical Treatment of Malpositions of the Uterus. PMID- 20313247 TI - The Surgical Treatment of Gastric and Duodenal Ulcer. PMID- 20313248 TI - A Clinical Study of the Pathology of Osteomyelitis. PMID- 20313249 TI - Syphilis, Its Relation to Infant Mortality and Child Welfare, with a Discussion of present Day Methods for Its Control. PMID- 20313251 TI - The Prevention of Small-Pox. PMID- 20313250 TI - Review of a Season's Quarantine Station work. PMID- 20313252 TI - Deaths from Cancer. PMID- 20313253 TI - The Treatment of Diabetes Mellitus. PMID- 20313254 TI - The Financing of Hospitals. PMID- 20313255 TI - The Caseins of Cows' Milk in Their Relations to Infant Feeding. PMID- 20313256 TI - Advances in Psychology. PMID- 20313257 TI - Foreword. PMID- 20313258 TI - Malignant Disease of the Throat. PMID- 20313259 TI - Experiences of an Otologist in France, 1915-1919. PMID- 20313260 TI - What Does Public Health Administration Embrace? PMID- 20313261 TI - The Relation of General Medicine to Mental Medicine. PMID- 20313262 TI - The Chlorination of Small Water Supplies. PMID- 20313263 TI - The Treatment of Acute Pelvic Inflammation in the Female. PMID- 20313264 TI - The X-ray Diagnosis of Gastric and Duodenal Ulcer. PMID- 20313265 TI - Prognosis and Diagnosis in Tuberculosis as Aided by Serology. PMID- 20313266 TI - Cancer of the Stomach. PMID- 20313268 TI - The Etiology of Rickets. PMID- 20313267 TI - Surgery of the Gallbladder and Biliary Ducts. PMID- 20313269 TI - Recent Advances in Our Knowledge of the Alkaloids of Opium. PMID- 20313270 TI - Surgery in the Treatment of Pulmonary Tuberculosis. PMID- 20313271 TI - Bronchial Asthma. PMID- 20313272 TI - Traumatic Aneurysm. PMID- 20313274 TI - Our Journal. PMID- 20313273 TI - A Surgical Curiosity. PMID- 20313275 TI - Oxygen Therapy. PMID- 20313276 TI - Anaesthesia in Nose and Throat Work. PMID- 20313277 TI - On the Lowering of Body Resistance Following Exposure to Cold. PMID- 20313278 TI - National Board of Medical Examiners in United States. PMID- 20313279 TI - Regarding Therapeutic Advertisements. PMID- 20313280 TI - Dr. Murdoch Chisholm. PMID- 20313281 TI - Re-Organization. PMID- 20313282 TI - Resolution Passed at Recent Dominion Convention of Amputations. PMID- 20313283 TI - Dialysis and transplatation. PMID- 20313284 TI - Precautionary labelling on preparations of retinoic acid. PMID- 20313285 TI - Role and training of paramedical groups. PMID- 20313286 TI - Behaviour modification. PMID- 20313287 TI - Invitation to contribute to aspects of national immunization policy. PMID- 20313288 TI - Health care and research in Canada. PMID- 20313289 TI - Openings for physicians in North Battleford, Sask. PMID- 20313290 TI - Medical applications of heroin. PMID- 20313291 TI - How social health insurance should be financed. PMID- 20313292 TI - Encouraging breast-feeding. PMID- 20313293 TI - "Winning isn't everything, it's the only thing". PMID- 20313294 TI - How social health insurance should be financed. PMID- 20313295 TI - Terminologic barbarianisms. PMID- 20313296 TI - "Sick slip" policy. PMID- 20313297 TI - Prevention of catheter emboliusm. PMID- 20313299 TI - Rebuttal from the post office. PMID- 20313298 TI - Rebuttal from the post office. PMID- 20313300 TI - MEBWITS syndrome. PMID- 20313301 TI - Family and child services act. PMID- 20313302 TI - Distribution of "Compendium of Pharmaceuticals and Specialties" to physicians. PMID- 20313303 TI - Distribution of "Compendium of Pharmaceuticals and Specialties" to physicians. PMID- 20313304 TI - Hazards of prenatal detection of neural tube defects. PMID- 20313305 TI - "The harvard guide to modern psychiatry". PMID- 20313307 TI - Salaried medical services. PMID- 20313306 TI - Scientific meeting epidemic. PMID- 20313309 TI - Henrietta banting memorial fund. PMID- 20313308 TI - Death attributed to ventricular arrhythmia. PMID- 20313311 TI - Primum non nocere. PMID- 20313310 TI - Dr. Christiaan barnard. PMID- 20313312 TI - Music therapy in palliative care. PMID- 20313313 TI - Dubiously helpful hints. PMID- 20313314 TI - Medical complications of obesity. PMID- 20313315 TI - The inconstant constant. PMID- 20313317 TI - Personal file. PMID- 20313316 TI - Who invented the decimal system? PMID- 20313318 TI - "The harvard guide to modern psychiatry". PMID- 20313319 TI - Clinical approach to the diagnosis of acid-base disorders. PMID- 20313321 TI - Personal file. PMID- 20313320 TI - The caduceus v. the staff of Aesculapius. PMID- 20313323 TI - Outflow of Canadian physicians. PMID- 20313322 TI - Advances in antibiotic prophylaxis in gastrointestinal surgery. PMID- 20313324 TI - Advertisements for tranquillizers. PMID- 20313325 TI - Ciguatera poisoning. PMID- 20313326 TI - Advertisements for tranquillizers. PMID- 20313327 TI - Position of Ontario podiatrists. PMID- 20313329 TI - Allied health professions. PMID- 20313328 TI - Allied health professions. PMID- 20313330 TI - Allied health professions. PMID- 20313331 TI - Letter from Scandinavia: a Swedish sabbatical. PMID- 20313332 TI - Personal file. PMID- 20313333 TI - CMA presidential election. PMID- 20313334 TI - CMA presidential election. PMID- 20313335 TI - CMA presidential election. PMID- 20313337 TI - Physicians opting out of medicare. PMID- 20313336 TI - "Medical hubris". PMID- 20313338 TI - Colour-blind drivers of motor vehicles. PMID- 20313340 TI - Personal file. PMID- 20313339 TI - Management of obstetric complications at a small rural hospital. PMID- 20313341 TI - Allied health professions. PMID- 20313342 TI - Personal file. PMID- 20313343 TI - Who was the first full-blooded North American Indian to receive an MD? PMID- 20313344 TI - Who was the first full-blooded North American Indian to receive an MD? PMID- 20313345 TI - Who was the first full-blooded North American Indian to receive an MD? PMID- 20313346 TI - Health care services in Canada. PMID- 20313348 TI - Personal file. PMID- 20313347 TI - Correct use of pressurized aerosol inhalers. PMID- 20313349 TI - Personal file. PMID- 20313351 TI - Are the goals of the Charter of Health for Canadians being achieved? Crombie appoints Emmett Hall to find out. PMID- 20313350 TI - What the community physician can do for Indochinese refugees. PMID- 20313352 TI - Modern medical education superior? PMID- 20313353 TI - Group B streptococcal infection in the newborn. PMID- 20313354 TI - Treatment of chemically dependent physicians. PMID- 20313355 TI - Quota of refugees from Vietnam. PMID- 20313356 TI - Violation of responsible publishing. PMID- 20313357 TI - Personal file. PMID- 20313358 TI - Breast-feeding: an aid to refraction. PMID- 20313359 TI - Aerosol bronchodilators. PMID- 20313360 TI - Personal file. PMID- 20313361 TI - Position papers passed by Canadian Psychiatric Association. PMID- 20313362 TI - Health problems of developing nations. PMID- 20313364 TI - Universal accessibility of medicare. PMID- 20313363 TI - Universal accessibility of medicare. PMID- 20313365 TI - Comforts of home in maternity wards. PMID- 20313366 TI - Starvation budget. PMID- 20313367 TI - Who is best qualified to care for the terminally ill? PMID- 20313368 TI - Metatarsophalangeal fusion for hallux valgus. PMID- 20313369 TI - Personal file. PMID- 20313370 TI - Are Christmas editorials appropriate for the Journal? PMID- 20313371 TI - Accreditation of Canadian medical schools. PMID- 20313372 TI - Harold benge atlee. PMID- 20313373 TI - Bilingualism in the journal. PMID- 20313374 TI - Colour-blind drivers of motor vehicles. PMID- 20313375 TI - Computed tomography and the early diagnostic lumbar puncture. PMID- 20313376 TI - Personal file. PMID- 20313377 TI - Colour-blind drivers of motor vehicles. PMID- 20313378 TI - Screening for overian cancer. PMID- 20313379 TI - Planning for psychiatric emergencies. PMID- 20313380 TI - The Canada Health Survey - who will pay for it? PMID- 20313381 TI - Vietnamese refugees. PMID- 20313382 TI - Psychiatric illness in physicians. PMID- 20313384 TI - Personal file. PMID- 20313383 TI - Vietnamese refugees. PMID- 20313385 TI - Personal file. PMID- 20313386 TI - Chiropractors. PMID- 20313387 TI - Chiropractors. PMID- 20313388 TI - Use of benzodiazepines. PMID- 20313389 TI - Health care services in Britain. PMID- 20313390 TI - How to be a successful investor. PMID- 20313391 TI - An opportunity to serve the community. PMID- 20313392 TI - Personal file. PMID- 20313393 TI - The hypertensive patient. PMID- 20313394 TI - Health care services in Britain. PMID- 20313395 TI - The Canada health survey. PMID- 20313396 TI - Piracy on the prairies. PMID- 20313397 TI - Left atrial myxoma mimicking vasculitis. PMID- 20313399 TI - Use of headphones in continuing medical education. PMID- 20313398 TI - Piracy on the prairies. PMID- 20313400 TI - 1. Design and main results of the trial. PMID- 20313401 TI - Personal file. PMID- 20313402 TI - Are flow charts obsolete? PMID- 20313403 TI - Drug information for patients. PMID- 20313405 TI - Personal file. PMID- 20313404 TI - Identification of impaired hearing in early childhood. PMID- 20313406 TI - Summary of the task force report on occupational respiratory disease. PMID- 20313408 TI - Malaria accompanied by unusual symptoms. PMID- 20313407 TI - Summary of the task force report on occupational respiratory disease. PMID- 20313409 TI - The periodic health examination. PMID- 20313411 TI - Are Christmas editorials appropriate for the Journal? PMID- 20313410 TI - Bilingualism in the journal. PMID- 20313412 TI - Doctors - free citizens? PMID- 20313413 TI - The periodic health examination. PMID- 20313414 TI - Classification of psychiatric disorders. PMID- 20313415 TI - Restrictions imposed by Federal Trade Commission. PMID- 20313417 TI - Speak softly and carry a big nightstick. PMID- 20313416 TI - A "physiologic" penicillin preparation. PMID- 20313418 TI - Detecting and preventing glaucoma. PMID- 20313419 TI - Dietary fluids and diarrhea in babies. PMID- 20313420 TI - Music therapy in palliative care. PMID- 20313421 TI - Bilingualism in the journal. PMID- 20313422 TI - Making a good journal better. PMID- 20313423 TI - Extra or balanced billing. PMID- 20313424 TI - A rational approach to dementia. PMID- 20313425 TI - Politics in the journal? PMID- 20313426 TI - The CMA: strong membership, realistic goals. PMID- 20313427 TI - Running into danger: heat stroke in competing runners. PMID- 20313428 TI - Primary prevention of heat stroke in Canadian long-distance runs. PMID- 20313429 TI - Asymptomatic acute rejection crisis after renal cadaveric transplantation. PMID- 20313430 TI - Are funerals worth the money? PMID- 20313431 TI - Are funerals worth the money? PMID- 20313432 TI - Are funerals worth the money? PMID- 20313433 TI - Artois-baillet latour health prize. PMID- 20313434 TI - Are funerals worth the money? PMID- 20313435 TI - The annual psychological. PMID- 20313436 TI - Sodium restriction for treatment of hypertension. PMID- 20313438 TI - Physician manpower: lies, damn lies and statistics? PMID- 20313437 TI - Sodium restriction for treatment of hypertension. PMID- 20313439 TI - The periodic health examination. PMID- 20313441 TI - Mammography. PMID- 20313440 TI - The periodic health examination. PMID- 20313442 TI - Cardiac defibrillation dosage: controversy resolving. PMID- 20313443 TI - Hall review could gather dust. PMID- 20313444 TI - And now, a word for our sponsor. PMID- 20313445 TI - The fine print of CMARSP. PMID- 20313446 TI - The fine print of CMARSP. PMID- 20313447 TI - Serum ferritin concentration and bone marrow iron stores. PMID- 20313448 TI - Chlorine: effect on thiamin concentration. PMID- 20313449 TI - Canadian national breast cancer screening study. PMID- 20313450 TI - Medical education in the 21st century. PMID- 20313451 TI - "Handbook of nonprescription drugs". PMID- 20313452 TI - Commercial interruptions. PMID- 20313453 TI - The periodic health examination. PMID- 20313454 TI - The use of diathermy in the presence of metal implants and cardiac pacemakers. PMID- 20313455 TI - Comments on Canada's older population. PMID- 20313456 TI - Environmental health: new role for MDs. PMID- 20313457 TI - Adapting the Journal's Scientific Section to the 1980s. PMID- 20313458 TI - Consent and the transfer of medical information. PMID- 20313459 TI - Mammography. PMID- 20313461 TI - Circumcision. PMID- 20313460 TI - Mammography. PMID- 20313462 TI - Lovable still the word for physicians but not for Journalists. PMID- 20313464 TI - "Is there a doctor on this flight?". PMID- 20313463 TI - "Is there a doctor on this flight?". PMID- 20313465 TI - Prohibition of ethical ban on advertising. PMID- 20313466 TI - Out-of-hospital resuscitation from cardiac arrest. PMID- 20313467 TI - Dr. Harold Benge Atlee: request for information. PMID- 20313468 TI - Chronic granulomatous otitis media. PMID- 20313469 TI - Alberta: medical brain centre of Canada? PMID- 20313470 TI - Emergency department staffing. PMID- 20313471 TI - Canadian Plasma Exchange Study Group needs input from physicians. PMID- 20313472 TI - A taxing problem solved. PMID- 20313474 TI - Hans selye. PMID- 20313473 TI - Treatment of chronic pulmonary disease. PMID- 20313475 TI - Take an Australian to lunch. PMID- 20313477 TI - Rynacrom nasal spray - correction. PMID- 20313476 TI - The periodic health examination. PMID- 20313478 TI - Back-to-the-landers: physicians try the rustic life. PMID- 20313479 TI - Patients' health and welfare to remain CMA's primary concern in the year ahead. PMID- 20313480 TI - Making clinical decisions. PMID- 20313481 TI - Specificity of antinuclear factor testing: what does specific mean? PMID- 20313482 TI - The periodic health examination. PMID- 20313483 TI - Casting light on Darwin's Ape. PMID- 20313484 TI - Psychiatry, humility and medicine. PMID- 20313485 TI - Correction in CPS. PMID- 20313486 TI - Hall is not lost. PMID- 20313487 TI - The periodic health examination. PMID- 20313489 TI - Mandatory continuing medical education. PMID- 20313488 TI - The periodic health examination. PMID- 20313490 TI - Mandatory continuing medical education. PMID- 20313491 TI - Some odd patterns of psychotropic self-medication. PMID- 20313492 TI - Long-distance running in the heat. PMID- 20313493 TI - Primary prevention of asthma in children. PMID- 20313495 TI - Can a 5000-year-old habit be all that bad? PMID- 20313494 TI - Suggested approach to cancer therapy. PMID- 20313496 TI - Bilingualism in the journal. PMID- 20313497 TI - Suggested approach to cancer therapy. PMID- 20313498 TI - Atlantoaxial dislocation and Down's syndrome. PMID- 20313499 TI - Bone marrow transplantation. PMID- 20313500 TI - Progressive rheumatoid arthritis. PMID- 20313501 TI - Physicians and the law. PMID- 20313502 TI - The Cairbed v. British airbed. PMID- 20313503 TI - Appeal from national association of part-time teachers. PMID- 20313504 TI - Physicians an endangered species? PMID- 20313505 TI - "Is there a doctor on this flight?". PMID- 20313506 TI - "Anatomy of an illness as perceived by the patient". PMID- 20313508 TI - Physicians as civil servants. PMID- 20313507 TI - Use of carcinoembryonic antigen in follow-up of patients with ovarian cancer. PMID- 20313509 TI - Improving emergency cardiac care. PMID- 20313510 TI - Chronic granulomatous otitis media. PMID- 20313511 TI - In-flight medical care. PMID- 20313512 TI - View from the top. PMID- 20313513 TI - Eradication of Rh hemolytic disease of the newborn. PMID- 20313515 TI - New public health movement? PMID- 20313514 TI - The fine print of CMARSP. PMID- 20313516 TI - Legal abortions among teenagers, 1974-78. PMID- 20313518 TI - Canada's medical reporters - keeping the public informed. PMID- 20313517 TI - Legal abortions among teenagers, 1974-78. PMID- 20313520 TI - Governments, chiropractors and MDs. PMID- 20313519 TI - Mail chauvinism. PMID- 20313521 TI - Physicians rally against threat of a nuclear epidemic. PMID- 20313522 TI - Physicians rally against threat of a nuclear epidemic. PMID- 20313523 TI - Physicians rally against threat of a nuclear epidemic. PMID- 20313524 TI - Clonidine for menopausal flushing. PMID- 20313525 TI - More pediatricians needed in neonatal intensive care services. PMID- 20313526 TI - The need for extended treatment of anaphylaxis. PMID- 20313527 TI - Elective delivery and the neonatal respiratory distress syndrome. PMID- 20313528 TI - Stand up and be counted. PMID- 20313529 TI - Medical manpower data: total cooperation vital and urgent. PMID- 20313530 TI - Canada's underfuelled health care system. PMID- 20313531 TI - Influenza vaccination: physician compliance with recommendations. PMID- 20313532 TI - The abortion issue. PMID- 20313534 TI - More anesthetists needed. PMID- 20313533 TI - Fluphenazine, trifluoperazine and perphenazine in Vacutainers. PMID- 20313535 TI - [Not Available]. PMID- 20313536 TI - Government without frills: we're still free to choose. PMID- 20313537 TI - Who can best judge quality of life? PMID- 20313538 TI - The periodic health examination. PMID- 20313539 TI - Detecting and preventing glaucoma. PMID- 20313540 TI - Atlantoaxial dislocation and Down's syndrome. PMID- 20313541 TI - How will the new wave of women graduates change the medical profession? PMID- 20313542 TI - The investigation of transport accidents. PMID- 20313543 TI - How an underwriter calculates a policyholder's risk. PMID- 20313544 TI - CMAJ and the family physician. PMID- 20313545 TI - [Not Available]. PMID- 20313546 TI - Unionization of doctors. PMID- 20313547 TI - "Doctor, my feet hurt". PMID- 20313548 TI - "Doctor, my feet hurt". PMID- 20313549 TI - Informed consent: still a doctor's dilemma. PMID- 20313550 TI - Metric won't decimate the medical profession. PMID- 20313551 TI - The periodic health examination. PMID- 20313553 TI - Is cervical cancer hereditary? PMID- 20313552 TI - Sexual inequity in medical care. PMID- 20313554 TI - Connaught labs to expand research, production and sales. PMID- 20313555 TI - Medical manpower: a view from the community hospital. PMID- 20313557 TI - A national association for suicide prevention. PMID- 20313556 TI - Congenital rubella in an Indochinese refugee in Manitoba. PMID- 20313558 TI - Malabsorption of medications after bypass surgery. PMID- 20313560 TI - Year of the disabled: real progress or academic exercise? PMID- 20313559 TI - Inadequecy of current requirements of licensure in family medicine. PMID- 20313561 TI - Mail chauvinism. PMID- 20313563 TI - Abortion: 1. Definitions and implications [correction]. PMID- 20313562 TI - "Clinical guide to transfusion - products and practices". PMID- 20313564 TI - An anniversary dedication: editorial excellence on your behalf. PMID- 20313565 TI - Influenza vaccination in Alberta, 1978: physician compliance with recommendations. PMID- 20313566 TI - Canadian interns and residents - the struggle for political maturity. PMID- 20313567 TI - Physicians rally against the threat of a nuclear epidemic. PMID- 20313569 TI - Is alcoholism a primary disease? PMID- 20313568 TI - Emergency drugs. PMID- 20313570 TI - The CMA, the College of Family Physicians of Canada and the medical students. PMID- 20313571 TI - Confusion between warfarin and propranolol. PMID- 20313572 TI - Fiscal arrangements task force: the CMA's chance to be heard. PMID- 20313573 TI - Osler oration. PMID- 20313574 TI - Osler oration. PMID- 20313575 TI - Inadequacy of current requirements for licensure in family medicine. PMID- 20313576 TI - Inadequacy of current requirements for licensure in family medicine. PMID- 20313577 TI - Inadequacy of current requirements for licensure in family medicine. PMID- 20313578 TI - Salaried medicine: salt mine or salvation? PMID- 20313580 TI - Recent donations to University of Manitoba libraries. PMID- 20313579 TI - Dissension in the ranks. PMID- 20313582 TI - My daughter the doctor. PMID- 20313581 TI - Reye's syndrome. PMID- 20313583 TI - Changes in regulations for registration of Canadian physicians in the United Kingdom. PMID- 20313584 TI - Proposed solution for lack of registered nurses. PMID- 20313585 TI - The changing role of the Canadian physician in the Third World. PMID- 20313586 TI - 1981: international year of disabled persons. PMID- 20313588 TI - The changing role of the Canadian physician in the Third World. PMID- 20313587 TI - The ontario mental health act. PMID- 20313589 TI - Informed consent. PMID- 20313591 TI - A convention of physicians; an incision of surgeons. PMID- 20313590 TI - Learning to cut health care costs. PMID- 20313592 TI - Medical macroeconomic myths. PMID- 20313593 TI - Politics and preventive medicine. PMID- 20313594 TI - Where have all the editorialists gone? PMID- 20313595 TI - "Doctor, my feet hurt". PMID- 20313597 TI - Tom Garry (1884-1963): a search for information. PMID- 20313596 TI - "Doctor, my feet hurt". PMID- 20313598 TI - Metric won't decimate the medical profession. PMID- 20313599 TI - Emergency medicine: two types of practice, three types of recognition? PMID- 20313600 TI - Vitamin A Acid: change in prescribing information. PMID- 20313602 TI - Peer review. PMID- 20313601 TI - This year in Halifax. PMID- 20313603 TI - Peer review. PMID- 20313604 TI - Inadequacy of current requirements for licensure in family medicine. PMID- 20313605 TI - Abortion. PMID- 20313606 TI - Chemonucleolysis. PMID- 20313607 TI - The Women's Clinic - at the frontiers of psychiatry. PMID- 20313608 TI - The Women's Clinic - at the frontiers of psychiatry. PMID- 20313609 TI - [Not Available]. PMID- 20313610 TI - Mail chauvinism revisited. PMID- 20313611 TI - Will offshore medical schools graduate quality physicians? PMID- 20313612 TI - The periodic health examination. PMID- 20313613 TI - Birthweight and handicaps. PMID- 20313614 TI - Antitumour activity of spleen extract. PMID- 20313615 TI - Theophylline and dyphylline. PMID- 20313616 TI - MD-MP contact: foundation of a successful lobby. PMID- 20313618 TI - "Unionized" medicine. PMID- 20313617 TI - High-Yield criteria for skull roentgenography. PMID- 20313619 TI - Physicians rally against the threat of a nuclear epidemic. PMID- 20313621 TI - The EPF task force report: malice in Wonderland. PMID- 20313620 TI - Compliance by physicians with the 1978 Ontario Mental Health Act. PMID- 20313622 TI - How to read clinical journals. PMID- 20313623 TI - Emergency medicine. PMID- 20313624 TI - New ways to learn? PMID- 20313625 TI - Family medicine certification. PMID- 20313626 TI - A flash in the pan. PMID- 20313627 TI - Harold rocke robertson. PMID- 20313628 TI - A sign of the times. PMID- 20313629 TI - My daughter the doctor. PMID- 20313630 TI - Family medicine certification. PMID- 20313631 TI - Sex education: the physician's role. PMID- 20313633 TI - The real Dr. Richard Goldbloom. PMID- 20313632 TI - Clocking out? PMID- 20313634 TI - Influenza virus vaccine for 1981-82. PMID- 20313635 TI - BC fee negotiations - an expensive victory? PMID- 20313636 TI - The doctor's dilemma: defining worth. PMID- 20313637 TI - Family medicine certification. PMID- 20313638 TI - Arthur vineberg. PMID- 20313639 TI - Stepping down: the end of an era of gentlemanly persuasion. PMID- 20313640 TI - Christmas 1981. PMID- 20313641 TI - Do physicians overprescribe for women with emotional problems? PMID- 20313643 TI - Family medicine certification. PMID- 20313642 TI - Potentially lethal interaction of cimetidine and morphine. PMID- 20313644 TI - Present views on the Canadian Home Fitness Test. PMID- 20313645 TI - Traffic injury research foundation of Canada. PMID- 20313646 TI - Swan-Ganz catheter. PMID- 20313647 TI - BC fee negotiations-an expensive victory? PMID- 20313648 TI - The question we have to decide. PMID- 20313649 TI - Access to medical literature. PMID- 20313650 TI - Access to medical literature. PMID- 20313651 TI - New Year resolutions: 10 words to give up in 1982. PMID- 20313652 TI - Letters to the editor. PMID- 20313653 TI - Family medicine certification. PMID- 20313654 TI - How to apply for a medical position in the Third World. PMID- 20313655 TI - The canadian medical directory. PMID- 20313656 TI - Trauma research. PMID- 20313657 TI - Good Samaritan laws: questioning the need. PMID- 20313658 TI - Training for family practice. PMID- 20313659 TI - Abortion. PMID- 20313661 TI - Mail chauvinism reversed. PMID- 20313660 TI - Anesthesiology. PMID- 20313663 TI - Good English is good medicine. PMID- 20313662 TI - Canadian trauma foundation. PMID- 20313664 TI - Access to the medical literature. PMID- 20313666 TI - Health for all by the year 2000. PMID- 20313665 TI - Placement incentives. PMID- 20313667 TI - Theodore brown rasmussen. PMID- 20313668 TI - The international year of the overtaxed. PMID- 20313669 TI - Ophthalmologists and optometrists. PMID- 20313670 TI - Continuing medical education in Maritime Canada. PMID- 20313671 TI - Good English is good medicine. PMID- 20313672 TI - Accuracy of clinical diagnosis. PMID- 20313673 TI - Good English is good medicine. PMID- 20313674 TI - Abortion before "individuation". PMID- 20313675 TI - Reducing government spending. PMID- 20313677 TI - Circumcision: the unkindest cut of all? PMID- 20313676 TI - Osteopathy. PMID- 20313678 TI - Chemonucleolysis. PMID- 20313679 TI - Treatment of acetaminophen poisoning. PMID- 20313680 TI - Benign breast disease. PMID- 20313681 TI - The pharmaceutical industry needs remedy for MacEachenism. PMID- 20313682 TI - Circumpolar health. PMID- 20313683 TI - Labour is still painful. PMID- 20313684 TI - Chalk river nuclear laboratories. PMID- 20313685 TI - Labour is still painful. PMID- 20313686 TI - Chalk river nuclear laboratories. PMID- 20313687 TI - Retrograde cholangiography. PMID- 20313688 TI - Circumcision. PMID- 20313689 TI - Friends and families of the handicapped. PMID- 20313690 TI - Hospitals and private money. PMID- 20313691 TI - Circumcision. PMID- 20313692 TI - Circumcision. PMID- 20313693 TI - Circumcision. PMID- 20313694 TI - Circumcision. PMID- 20313695 TI - Circumcision. PMID- 20313696 TI - Labour is still painful. PMID- 20313697 TI - The hospital: a place of comfort or a place of work? PMID- 20313698 TI - The medical profession and the press: prime targets for commissions, task forces. PMID- 20313699 TI - Abortion. PMID- 20313700 TI - Circumcision. PMID- 20313701 TI - The psychiatrist's role in the care of the elderly. PMID- 20313702 TI - Family medicine certification. PMID- 20313703 TI - The iatrectomists. PMID- 20313704 TI - Physicians and the bomb. PMID- 20313705 TI - Physicians and the bomb. PMID- 20313706 TI - Physicians and the bomb. PMID- 20313707 TI - Mr. Woods replies. PMID- 20313708 TI - Geriatric medicine. PMID- 20313709 TI - Geriatric medicine. PMID- 20313710 TI - Declining rates of death due to heart disease. PMID- 20313711 TI - Cuber's thumb. PMID- 20313712 TI - Is Ottawa a capital punishment? PMID- 20313713 TI - Declaration of Vancouver updated. PMID- 20313714 TI - Mortality and medicine. PMID- 20313715 TI - Prescribing of tranquillizers. PMID- 20313716 TI - Prescribing of tranquillizers. PMID- 20313717 TI - Ten words to give up in 1982. PMID- 20313718 TI - Circumcision. PMID- 20313719 TI - Are routine measurements of serum chloride and total carbon dioxide levels worth doing? PMID- 20313720 TI - Canada's first medical graduate. PMID- 20313721 TI - How to apply for a medical position in the Third World. PMID- 20313722 TI - Guide on infant feeding. PMID- 20313723 TI - Diagnosis and treatment of low blood pressure in a Canadian community. AB - When some participants in a hypertension screening program reported a previous diagnosis or treatment of low blood pressure a similar program was established at two shopping centres in Montreal to identify and characterize subjects labelled as having low blood pressure. Of the 1019 subjects screened (434 men and 585 women) 275 (27.0%) reported a previous diagnosis of low blood pressure and 278 (27.3%) a previous diagnosis of hypertension. Low blood pressure was significantly more likely to be diagnosed in women than in men. Of the 181 subjects reporting a diagnosis of low blood pressure in the absence of other diagnoses, 69 had received treatment for this condition; fewer than 10 years of education had been completed by 46.4% of the treated subjects and 34.8% of those not treated, compared with 20.0% of the subjects in whom no diagnosis had been made. Assuming that these findings do not reflect an idiosyncrasy of the community or of the population studied, the public and personal health implications of the erroneous diagnosis and treatment of this nondisease need to be assessed. PMID- 20313724 TI - The economy: an anthropologic view. PMID- 20313725 TI - Oral history. PMID- 20313726 TI - Occupational cancer: experience in Ontario. PMID- 20313727 TI - Sex education: the physician's role. PMID- 20313728 TI - Abortion. PMID- 20313729 TI - Abortion. PMID- 20313730 TI - Tribulations of a clinical trial. PMID- 20313731 TI - Prescribing tranquillizers. PMID- 20313732 TI - Determining the site of urinary tract infections in children. PMID- 20313734 TI - The ethics of biomedicine. PMID- 20313733 TI - An appeal to CMA members. PMID- 20313735 TI - Task force on provision of primary care services. PMID- 20313736 TI - The international year of the overtaxed. PMID- 20313737 TI - The age of consent. PMID- 20313738 TI - Generic names. PMID- 20313739 TI - Scientifically trained allergists. PMID- 20313740 TI - Scientifically trained allergists. PMID- 20313741 TI - The international year of the overtaxed. PMID- 20313742 TI - The international year of the overtaxed. PMID- 20313743 TI - The international year of the overtaxed. PMID- 20313744 TI - Smoking habits in hospital. PMID- 20313746 TI - Abortion. PMID- 20313745 TI - Abortion. PMID- 20313747 TI - Ten words to give up in 1982. PMID- 20313749 TI - Ottawa's Blue Book: the true story on Medicare funding. PMID- 20313748 TI - Jacques genest. PMID- 20313750 TI - Microcomputers in medicine. PMID- 20313751 TI - Computers in medicine: a publishing dilemma. PMID- 20313752 TI - Directory of cancer support services in Ontario. PMID- 20313753 TI - Index Medicus jeopardized. PMID- 20313754 TI - How to write a certificate. PMID- 20313755 TI - Treatment of acetaminophen poisoning. PMID- 20313756 TI - Circumcision. PMID- 20313757 TI - Circumcision. PMID- 20313758 TI - Letters to the editor: variety and brevity. PMID- 20313759 TI - Bronchoalveolar lavage. PMID- 20313760 TI - Ear-crease sign and coronary artery disease. PMID- 20313761 TI - How to read clinical journals. PMID- 20313762 TI - Labour pain. PMID- 20313763 TI - Everett chalmers. PMID- 20313765 TI - Mononucleosis. PMID- 20313764 TI - Rationalizing medicare. PMID- 20313767 TI - Fight "long hours", "normal", "convince" and the split infinitive. PMID- 20313766 TI - Declaration of vancouver. PMID- 20313768 TI - Technocrats in Quebec health care: time to say "Stop!". PMID- 20313770 TI - The general medical licence. PMID- 20313769 TI - Bone marrow transplantation in Canada. PMID- 20313771 TI - Ottawa: a capital punishment? PMID- 20313772 TI - Volvolon. PMID- 20313773 TI - Communities and Indian health. PMID- 20313774 TI - Gerald halpenny. PMID- 20313775 TI - Saskatoon has POW. PMID- 20313776 TI - Winning friends in, and influencing, government. PMID- 20313777 TI - Sex education. PMID- 20313778 TI - Sex education. PMID- 20313780 TI - Preparing fo family medicine. PMID- 20313779 TI - Preparing for family medicine. PMID- 20313781 TI - Preparing for family medicine. PMID- 20313782 TI - A case of familial lingua bifida? PMID- 20313783 TI - Low blood pressure. PMID- 20313784 TI - The pharmaceutical industry. PMID- 20313785 TI - Medical services for outdoor rock music festivals. PMID- 20313786 TI - Controlling the medical information balloon. PMID- 20313787 TI - The "limitations" of medicine. PMID- 20313788 TI - Nothing to fear but FIRA itself. PMID- 20313789 TI - Circumcision. PMID- 20313790 TI - Why I won't practise in the United States. PMID- 20313792 TI - Update on products containing tartrazine. PMID- 20313791 TI - Opting out: what's the real issue? PMID- 20313793 TI - Update on products containing tartrazine. PMID- 20313794 TI - Robert orville jones. PMID- 20313795 TI - Antibusiness attitudes strangling drug research. PMID- 20313796 TI - Reactions to acetylsalicylic acid. PMID- 20313797 TI - Reactions to acetylsalicylic acid. PMID- 20313799 TI - Omission from 1982 "Compendium of-Pharmaceuticals and Specialties". PMID- 20313798 TI - Interaction between immunologic and chemotherapeutic treatments. PMID- 20313800 TI - Ampyutashuns of terminashuns. PMID- 20313801 TI - Volvolon. PMID- 20313802 TI - Placement or disposal? PMID- 20313803 TI - Apparent differences in longevity. PMID- 20313805 TI - Health economists: our growing need for innovators. PMID- 20313804 TI - Involuntary admission in Ontario. PMID- 20313806 TI - Ethical issues in sponsorship of CME. PMID- 20313807 TI - "Radiation & human health". PMID- 20313808 TI - Should psychiatrists perform physical examinations? PMID- 20313809 TI - Interferon: no verdict yet. PMID- 20313811 TI - The future of Canadian hospitals. PMID- 20313810 TI - George william manning. PMID- 20313812 TI - Dr. Ernest j. Clifford. PMID- 20313813 TI - Ontario Medical Association: a view from abroad. PMID- 20313814 TI - Lack of interest in nutrition? PMID- 20313815 TI - Peter banks. PMID- 20313816 TI - Getting drug information to the practising physician. PMID- 20313817 TI - Drug prescription labels. PMID- 20313818 TI - Information sought on 1918 influenza epidemic. PMID- 20313819 TI - Benefits of CMA membership. PMID- 20313820 TI - Underfunding's effect on Canadian hospitals. PMID- 20313821 TI - Spinal injuries due to hockey. PMID- 20313822 TI - New Year resolutions: 10 words to give up in 1983. PMID- 20313823 TI - Medical manpower planning: mission impossible? PMID- 20313824 TI - Abortion. PMID- 20313825 TI - Underfunding's effect on Canadian hospitals. PMID- 20313826 TI - Sex role ideology. PMID- 20313827 TI - Professional responsibilities. PMID- 20313828 TI - Robert alexander mustard. PMID- 20313829 TI - 2nd world congress on prison health care. PMID- 20313830 TI - Lawren harris. PMID- 20313831 TI - Dr. F.N.g. Starr. PMID- 20313832 TI - Appraisal of pediatric cardiopulmonary resuscitation. PMID- 20313833 TI - US hospitals turn to private funds. PMID- 20313835 TI - Letter from the editor. PMID- 20313834 TI - Can physicians cope with recession medicine? PMID- 20313836 TI - Should psychiatrists perform physical examinations? PMID- 20313837 TI - Administration and physicians. PMID- 20313838 TI - [Not Available]. PMID- 20313839 TI - Norman charles delarue. PMID- 20313840 TI - Cruising the Greek islands. PMID- 20313841 TI - International committee of medical journal editors. PMID- 20313842 TI - Rheumatoid arthritis. PMID- 20313843 TI - In praise of eloquence. PMID- 20313844 TI - The vanishing clinician-scientist. PMID- 20313846 TI - Convention cities: Monte Carlo. PMID- 20313845 TI - The vanishing clinician-scientist. PMID- 20313847 TI - We're all government workers nowadays. PMID- 20313848 TI - The beautiful manuscript. PMID- 20313849 TI - Detecting breast cancer. PMID- 20313850 TI - Smoking in Canada. PMID- 20313851 TI - Idiotic and inhuman architecture. PMID- 20313852 TI - Coronary ostial stenosis. PMID- 20313853 TI - Numbering fingers. PMID- 20313855 TI - Douglas george cameron. PMID- 20313854 TI - Why nicotinic acid lowers lipid levels. PMID- 20313856 TI - Medical technology: opportunities, responsibilities. PMID- 20313857 TI - Medical Science News: recent, relevant and refined. PMID- 20313858 TI - Violence against self and others. PMID- 20313859 TI - CMA statement on radiation protection. PMID- 20313860 TI - Is professional courtesy dying? PMID- 20313861 TI - Canadian physicians in the United States. PMID- 20313862 TI - Writing psychiatric reports. PMID- 20313863 TI - Writing psychiatric reports. PMID- 20313864 TI - Additional uses for depot medroxyprogesterone acetate? PMID- 20313866 TI - Psychiatric symptoms following attempted natural childbirth. PMID- 20313865 TI - Research in family medicine. PMID- 20313867 TI - Cancer in a Montreal suburb. PMID- 20313868 TI - [Not Available]. PMID- 20313869 TI - Medicine in the 21st century: 1. The coming of the corporations. PMID- 20313870 TI - Bringing out the best in a manuscript. PMID- 20313871 TI - Words to give up in 1983. PMID- 20313872 TI - CMAJ covers. PMID- 20313873 TI - Religion, science and faith. PMID- 20313874 TI - Words to give up in 1983. PMID- 20313875 TI - Increasing compliance with prescribed medication by elderly patients. PMID- 20313876 TI - Nuclear disarmament. PMID- 20313877 TI - Nuclear disarmament. PMID- 20313878 TI - Lack of interest in nutrition? PMID- 20313879 TI - Boxing. PMID- 20313880 TI - Charles Darwin's illness. PMID- 20313881 TI - Convention cities: San Francisco. PMID- 20313882 TI - Jonathan fayette meakins. PMID- 20313883 TI - The CMA president responds to Monique Begin's letter. PMID- 20313884 TI - Bilirubin levels in breast-fed infants. PMID- 20313886 TI - Answers to money and practice management questions. PMID- 20313885 TI - Bilirubin levels in breast-fed infants. PMID- 20313887 TI - What do the nurses want? PMID- 20313888 TI - Religion, science and faith. PMID- 20313889 TI - Religion, science and faith. PMID- 20313890 TI - The cover: something for the right hemisphere. PMID- 20313891 TI - CMAJ covers. PMID- 20313892 TI - Eye drops and apnea. PMID- 20313893 TI - Lightning injury. PMID- 20313894 TI - Pharmaceutical firms and Canadian regulations. PMID- 20313895 TI - Dr. Mercer Rang and teaching with humour. PMID- 20313896 TI - "I don't want an x-ray, Doctor". PMID- 20313898 TI - The Josephinum: a glimpse into Austria's distinguished past. PMID- 20313897 TI - Open letter on family practice training. PMID- 20313899 TI - Gordon bethune. PMID- 20313900 TI - Accrediting Canadian medical schools. PMID- 20313901 TI - The doctors who treat performing artists. PMID- 20313902 TI - Will Britain's National Health Service survive? PMID- 20313903 TI - Avoiding the bedint. PMID- 20313904 TI - This is not the place to blow your top or vent your spleen. PMID- 20313905 TI - Dr. Earle scarlett. PMID- 20313906 TI - Numbering fingers. PMID- 20313907 TI - Canadian public trusts the CMA. PMID- 20313908 TI - Delayed elimination of theophylline in pregnancy. PMID- 20313910 TI - CARE/Medico in Afghanistan. PMID- 20313909 TI - Overdoses of entrophen. PMID- 20313911 TI - Physiotherapists. PMID- 20313912 TI - Paul h.T. Thorlakson. PMID- 20313913 TI - Patients' rights: the one that really counts. PMID- 20313914 TI - Quebec physicians and the government yoke: the Social Affairs minister responds. PMID- 20313915 TI - Dr. Mercer Rang responds. PMID- 20313916 TI - What does Monique Begin mean by "administrative costs"? PMID- 20313917 TI - How does the Lalonde budget affect you? PMID- 20313918 TI - Is CMAJ "right wing"? PMID- 20313919 TI - Medical manpower planning. PMID- 20313920 TI - Medical manpower planning. PMID- 20313921 TI - Pedaller's penis: a 100-year-old delayed reaction. PMID- 20313922 TI - Is professional courtesy dying? PMID- 20313923 TI - Is professional courtesy dying? PMID- 20313924 TI - "Handbook of clinical drug data". PMID- 20313925 TI - John burnett neilson. PMID- 20313926 TI - Pants, trousers and community medicine. PMID- 20313927 TI - User fees and fiscal sense. PMID- 20313928 TI - The importance of being cited. PMID- 20313929 TI - Ageing, fitness and morbidity. PMID- 20313930 TI - What do the nurses want? PMID- 20313931 TI - Getting the right words in the right place. PMID- 20313932 TI - What do the nurses want? PMID- 20313933 TI - Correction to the "compendium of pharmaceuticals and specialties". PMID- 20313935 TI - Canada Fitness Survey finds fitness means health. PMID- 20313934 TI - A. Ross tilley. PMID- 20313936 TI - Convention cities: Lisbon. PMID- 20313937 TI - The emperor's new clothes. PMID- 20313938 TI - Pictures, symbols, charts and graphs. PMID- 20313939 TI - Government money: where did it go? PMID- 20313940 TI - Should we stamp out or give a hand to new journals? PMID- 20313941 TI - Hypertension. PMID- 20313942 TI - Do we need doctors in the health care system? PMID- 20313943 TI - Nurd knuckles. PMID- 20313944 TI - Health economics: Are Australians ahead of Canadians? PMID- 20313945 TI - Medicine in the 21st century: 2. The geriatric imperative. PMID- 20313946 TI - Can a speech make a good journal article? PMID- 20313947 TI - Abortion. PMID- 20313948 TI - Neonatal circumcision. PMID- 20313949 TI - Harry medovy. PMID- 20313950 TI - CMA's meeting in Monte Carlo: rien ne va plus? PMID- 20313951 TI - First write it down, then write it up. PMID- 20313952 TI - The beautiful editorial response. PMID- 20313953 TI - Adolescent nutrition, 2. Normal nutritional requirements. PMID- 20313955 TI - General Council: the CMA's parliament. PMID- 20313954 TI - Convention cities: Helsinki. PMID- 20313956 TI - "Alice in numberland"? PMID- 20313957 TI - "Alice in numberland"? PMID- 20313958 TI - Humane medicine. PMID- 20313959 TI - The josephinum. PMID- 20313960 TI - Recognizing organic mental disorders. PMID- 20313961 TI - Incentive pay with the Veterans Administration. PMID- 20313962 TI - Covering the literature. PMID- 20313964 TI - Pitseolak ashoona. PMID- 20313963 TI - High index of suspicion. PMID- 20313965 TI - Health care costs. PMID- 20313966 TI - Hominem, feminam or personam? PMID- 20313967 TI - CMAJ covers. PMID- 20313968 TI - Directory of cancer support services in Ontario. PMID- 20313970 TI - Gallup on hospital user fees. PMID- 20313969 TI - Sodium intoxication causded by use of baking soda as a home remedy. PMID- 20313972 TI - Helping the impaired physician. PMID- 20313971 TI - French articles in CMAJ. PMID- 20313973 TI - Helping the impaired physician. PMID- 20313974 TI - Cochlear implants. PMID- 20313975 TI - Alcoholism in medical school curricula. PMID- 20313976 TI - Role of prostitution in sexually transmitted diseases. PMID- 20313977 TI - Radiography for acute ankle injuries. PMID- 20313978 TI - Medical magazines: another view. PMID- 20313979 TI - Canada Health Act: a plan of attack. PMID- 20313980 TI - Theft of prescription pads. PMID- 20313981 TI - Breast self-examination. PMID- 20313982 TI - Update on products containing tartrazine. PMID- 20313983 TI - Abortion and the demographic argument. PMID- 20313984 TI - Amebic colitis. PMID- 20313986 TI - An appeal for books. PMID- 20313985 TI - Neonatal lupus erythematosus. PMID- 20313987 TI - Phil gold. PMID- 20313988 TI - Managing Canada's health care system. PMID- 20313989 TI - Convention cities: Honolulu. PMID- 20313990 TI - The chimera of preventive medicine in reducing health care costs. PMID- 20313991 TI - Breast cancer. PMID- 20313992 TI - Reiter's syndrome? PMID- 20313993 TI - "Compendium of pharmaceuticals and specialties". PMID- 20313994 TI - Quebec: towards a new national awareness. PMID- 20313995 TI - Ethics of informed consent. PMID- 20313996 TI - Erectile impotence. PMID- 20313997 TI - Edwin Clarence McCoy. PMID- 20313998 TI - When reviewers disagree. PMID- 20313999 TI - BCG in the treatment of cancer. PMID- 20314001 TI - Are you sure that device is working? PMID- 20314000 TI - "Junk mail". PMID- 20314002 TI - New Year resolutions: 10 words to give up in 1984. PMID- 20314003 TI - Writing-and recognizing-the final draft of a manuscript. PMID- 20314004 TI - Bureaucratic meddling in medicine. PMID- 20314005 TI - The CMA abortion survey. PMID- 20314006 TI - The CMA abortion survey. PMID- 20314007 TI - The CMA abortion survey. PMID- 20314008 TI - Dr. T. Clarence routley. PMID- 20314010 TI - CMAJ covers. PMID- 20314009 TI - CMAJ covers. PMID- 20314011 TI - Arthur birt. PMID- 20314013 TI - Doctors on the slopes. PMID- 20314012 TI - How to hire your office staff. PMID- 20314014 TI - Pregnancy and Tuberculosis : Part I-The Effects of Pregnancy on Tuberculosis. PMID- 20314015 TI - Technique of Cataract Operations. PMID- 20314016 TI - Observations on the Aetiology of Infantile Eczema. PMID- 20314017 TI - Some New Anaesthetic Ethers. PMID- 20314018 TI - The Sodium Citrate Technique for Blood Transfusion. PMID- 20314019 TI - Hour Glass Stomach. PMID- 20314020 TI - Two Cases of Supernumerary Ureters Opening Intravesically. PMID- 20314021 TI - A Psychosis of Hysterical Type. PMID- 20314022 TI - The Treatment of Chronic Nephritis. PMID- 20314023 TI - Acute Poliomyelitis. PMID- 20314024 TI - Medical Studies at Paris. PMID- 20314025 TI - A Sketch of Renal Diagnostic Methods. PMID- 20314026 TI - Methods of Study of Early Diabetes. PMID- 20314027 TI - On the Value of Drugs in Affections of the Urinary Tract. PMID- 20314028 TI - Canadian Medico-legal Jurisprudence. PMID- 20314029 TI - On Therapeutical and Pharmaceutical Problems. PMID- 20314030 TI - Elixir Lactopeptine. PMID- 20314031 TI - On Globeol. PMID- 20314033 TI - A Comparative Study of Measles and German Measles. PMID- 20314032 TI - Iodides and Bromides in Mixtures. PMID- 20314034 TI - Pregnancy and Tuberculosis : Part 2.-The Treatment of Tuberculosis Complicated by Pregnancy. PMID- 20314035 TI - Arteriosclerosis and Angina Pectoris with Temporary Muscular Paralysis. PMID- 20314036 TI - A Case of Acute Obstruction Due to Cystic Dilatation of the Appendix (Hydrops of Appendix). PMID- 20314038 TI - The Quinidin Treatment of Auricular Fibrillation. PMID- 20314037 TI - Raynaud's Disease of Four Years' Duration, Acute Fatal Termination with Signs of Involvement of Arteries of Central Nervous System. PMID- 20314039 TI - On the Nature and Origin of the Anginal Syndrome. PMID- 20314040 TI - Simple Goitre in Man.-Its Prevention and Treatment. PMID- 20314041 TI - Bodily Temperature and Hibernation. PMID- 20314042 TI - Asaya-Neural. PMID- 20314043 TI - Flavouring. PMID- 20314044 TI - Tincture of Digitalis. PMID- 20314045 TI - THE ASSOCIATION. PMID- 20314046 TI - Dr. Thos. Wickett. PMID- 20314047 TI - CORRESPONDENCE. PMID- 20314048 TI - The Outlook in Surgery. PMID- 20314049 TI - Some Problems in Intracranial Diagnosis. PMID- 20314050 TI - Financial Considerations of the Average Doctor. PMID- 20314051 TI - A Call-in Report on the Late Results of Surgical Treatment of Constricting Bands of the Large Intestine Terminal Ileum. PMID- 20314052 TI - Lessons Learned from a Study of the Gall Bladder. PMID- 20314053 TI - The Operative Treatment of Vesico-Vaginal FistulAE. PMID- 20314054 TI - Circumscribed Syphilitic Ulcer of the Stomach: Report of a Case. PMID- 20314055 TI - Vagino-Vesical and Utero-Vesical Fistulae.-Operative Treatment. PMID- 20314056 TI - Some Tendencies in Modern Clinical Medicine. PMID- 20314058 TI - A Rational Treatment of Surgical Shock Based on Proven Physiological Data. PMID- 20314057 TI - "Marrow Pains" in Malaria and in Certain Other Acute Fevers. PMID- 20314059 TI - Anterior Poliomyelitis. PMID- 20314060 TI - Pancreatic Extracts in the Treatment of Diabetes Mellitus. PMID- 20314061 TI - The Blood Cholesterol-Its Importance, and the Value of its Determination in Cancer Research. PMID- 20314062 TI - Problems of Clinical Interest to the Surgeon and Radium Therapist Relating to Cancer. PMID- 20314063 TI - A Statistical Study of Seventy-seven Cases of Tuberculous Meningitis. PMID- 20314064 TI - Heart Block and Auricular Fibrillation. PMID- 20314065 TI - Septic Abortion. PMID- 20314066 TI - Observations on the Value of Lumbar Puncture. PMID- 20314067 TI - Anaesthesia for Nose, Throat and Abdominal Surgery by Nitrous Oxide-Oxygen C. E. Combinations. PMID- 20314068 TI - Case Reports from Montreal General Hospital. PMID- 20314069 TI - Tuberculous Meningitis Simulating Encephalitis Lethargica Haemorrhagica. PMID- 20314070 TI - On the Parkinsonian Syndrome. PMID- 20314071 TI - The Laboratory Worker and the Practitioner. PMID- 20314072 TI - On the Relation between Mental and Physical Efficiency. PMID- 20314073 TI - On the Value of Various Kinds of Soaps as Antiseptics in Hand Washing. PMID- 20314074 TI - Smaller Hospitals and their Clinical Possibilities. PMID- 20314075 TI - Embryology and Physiology of Colonic Stasis. PMID- 20314076 TI - The Next Great Advance in Medicine. PMID- 20314077 TI - Glimpses into Endocrinology. PMID- 20314078 TI - Introductory Remarks. PMID- 20314079 TI - History in Tuberculosis. PMID- 20314080 TI - Toxic Goitre: The Effect of Thyroidectomy on the Basal Rate, the Pulse Rate, and the General Nutrition. PMID- 20314081 TI - The Cancer Problem. PMID- 20314082 TI - Thyroid Function from a Chemical View-Point. PMID- 20314083 TI - The Acute Appendix. PMID- 20314084 TI - Favus: A Report of Seventeen Cases. PMID- 20314085 TI - Intubation vs. Tracheotomy. PMID- 20314086 TI - Uterine Haemorrhage from the Viewpoint of the General Practitioner. PMID- 20314087 TI - Nephrolithiasis, Pyonephrosis and Impacted Urethral Calculus in a Boy Four Years of Age. PMID- 20314088 TI - A Case of Anus Vestibularis; Reconstruction with Successful Result. PMID- 20314090 TI - The Parkinsonian Syndrome: (Part Two). PMID- 20314089 TI - The Problem of the Control of Diphtheria. PMID- 20314092 TI - On the Treatment of the Tuberculous Ex-Service Man. PMID- 20314091 TI - On the Danger of Ex-Service Men with no Medical Knowledge attempting Osteopathy or so-called Chiropraxis. PMID- 20314093 TI - The Octo Centenary of St. Bartholomew's School. PMID- 20314094 TI - On Standardization. PMID- 20314095 TI - Robert C. Paterson Memorial Fund. PMID- 20314096 TI - Coagulants and Haemorrhage. PMID- 20314097 TI - Tuberculosis Congress in Brussels. PMID- 20314098 TI - On the Claims of Chiropractics. PMID- 20314099 TI - Clinical Lecture. Carcinoma of Rectum. PMID- 20314100 TI - Aortic Dilatation and Aneurism. PMID- 20314101 TI - The Pathology and Treatment of Chronic Catarrhal Deafness. PMID- 20314102 TI - Notes on the Newer Pathology of Syphilis. PMID- 20314103 TI - "Symptoms of Recovery". PMID- 20314104 TI - The Treatment of So-called Sciatica. PMID- 20314105 TI - Notes on Tetanus. PMID- 20314106 TI - On the Relationship between the Adrenal Gland and the Thyroid. PMID- 20314107 TI - Differential Diagnosis of Diseases of the Thyroid Gland. PMID- 20314108 TI - Symposium on Tuberculosis Physical Signs. PMID- 20314109 TI - Notes on Two Cases of Rheumatoid Arthritis. PMID- 20314110 TI - Ulcerative Colitis due to Bacillus Dysenteriae, Simulating Pernicious Anaemia. PMID- 20314111 TI - Intermittent Hydronephrosis due to Kinking of the Right Ureter by an Accessory Renal Artery. PMID- 20314113 TI - Suppurative Parotitis. PMID- 20314112 TI - Purpura Haemorrhagica Complicated by Gangrene of the Glans Penis and Lung Abscess. PMID- 20314114 TI - Syphilitic Aortitis and Endocarditis. PMID- 20314115 TI - Diagnosis Uncertain, Help Wanted. PMID- 20314116 TI - Orthopaedics. PMID- 20314117 TI - Group Medicine. PMID- 20314118 TI - Diet and Hyperthyroidism. PMID- 20314119 TI - On the Causes which tend to Lower the Standard of Health in a Country. PMID- 20314120 TI - On the Etiology of Rickets. PMID- 20314121 TI - The Surgeon's Soliloquy on the Gall-Bladder. PMID- 20314122 TI - THE ASSOCIATION. PMID- 20314123 TI - Spinal Pressure. PMID- 20314124 TI - The Broadening Scope of Mental Medicine. PMID- 20314125 TI - Symptoms in Diagnosis of Pulmonary Tuberculosis, (Symposium on Tuberculosis). PMID- 20314126 TI - Differential Diagnosis, (Symposium on Tuberculosis. PMID- 20314127 TI - A Tuberculosis Survey of 1346 School Children in Saskatchewan. PMID- 20314128 TI - Ergot, Quinine and Pituitrin. PMID- 20314129 TI - A Report on Recent Metabolic findings in the diagnosis and Treatment of Diseases of the Thyroid Gland. PMID- 20314130 TI - Intestinal Obstruction. PMID- 20314131 TI - Creatinuria in Certain Diseased Conditions. PMID- 20314133 TI - The Place of Drugs in Medical Treatment. PMID- 20314132 TI - Intravenous Injection of a New Mercurial in Treatment of Syphilis. PMID- 20314134 TI - Caesarian Section. PMID- 20314135 TI - The X-Ray Examination, (Symposium on Tuberculosis). PMID- 20314136 TI - The New Order. PMID- 20314137 TI - Carcinoma of the Prostate. PMID- 20314138 TI - Obiter Scripta. PMID- 20314139 TI - A Note on the Incubation Period of Encephalitis Lethargica. Report of a Case Developing within Five Days of Exposure. PMID- 20314140 TI - The Etiology of Cancer. PMID- 20314141 TI - Pancreatic Extract and Diabetes. PMID- 20314142 TI - Treatment of Diabetes Mellitus by Pancreatic Extracts. PMID- 20314143 TI - The Aftermath of Encephalitis Lethargica. PMID- 20314144 TI - On the Necessity for the Careful Medical Oversight of Children of the School And Pre-School Age. PMID- 20314145 TI - The Action of High Altitudes on the Blood. PMID- 20314146 TI - The Address of the President of the Ontario Medical Association. PMID- 20314147 TI - Syphilis-Three Years' Observation. PMID- 20314148 TI - The Medical Care of Post-Operative Abdominal Cases. PMID- 20314149 TI - Infantile Eczema. PMID- 20314150 TI - Exanthem Subitum-Report of Five Cases. PMID- 20314151 TI - Formol-gel Reaction in the Blood Serum of Syphilitics. PMID- 20314152 TI - The Clinical Diagnosis of Syphilis. PMID- 20314153 TI - Pyelitis During Pregnancy and the Puerperium. PMID- 20314154 TI - The Use of X-Rays in Diseases of the Skin. PMID- 20314155 TI - Eye Conditions in Pregnancy. PMID- 20314156 TI - A Simple Cross Agglutination Test for Blood Donors, Using Hemolysed Blood. PMID- 20314157 TI - Broncho-Pneumonia following Aspiration of Zinc Stearate Powder. PMID- 20314159 TI - Bulletin of Harvey Club, London. PMID- 20314158 TI - Phlegmonous Gastritis with Cirrhosis of Liver. PMID- 20314160 TI - Is the Gall Bladder a Useless Organ. PMID- 20314161 TI - On the Diagnosis of Tuberculosis in Childhood. PMID- 20314162 TI - Pasteur Centenary Celebration. PMID- 20314163 TI - Standardization of Drugs. PMID- 20314164 TI - Purifico. PMID- 20314165 TI - X-Ray and Clinical Findings in Normal Chest of Children-6 to 10 years.-National Tuberculosis Association Medical Research. PMID- 20314166 TI - Some Hospitalization Problems-Hospital Standardization. PMID- 20314167 TI - The Evolution of Surgery as I have seen it in my own Practice. PMID- 20314168 TI - Typhoid Fever in Infancy and Childhood. PMID- 20314169 TI - The Effects of Ultra Violet Rays on the Calcium and Inorganic Phosphate Content of the Blood Serum of Rachitic Infants. PMID- 20314170 TI - Some Observations on the Starvation Treatment of Epilepsy. PMID- 20314171 TI - Post Operative Complications of the Respiratory Tract. PMID- 20314172 TI - Some Work with Block and Local Anaesthesia. PMID- 20314173 TI - A Statistical Study of Fermentative Diarrhoea, Infectious Diarrhoea, Acute Intestinal Intoxication and Decomposition Occurring in the Hospital for Sick Children, from October 1st, 1919, to October 1st, 1920, considering especially the relation of age, weight and parenteral infections to mortality. PMID- 20314174 TI - Fear-A Harmful Emotion, how may we eliminate it from the Surgical Patient's Mind? PMID- 20314175 TI - The Value of the Wassermann. PMID- 20314176 TI - The Effects of General Anaesthetics on the Liver. PMID- 20314177 TI - Report of a Case of Bromide Eruption in a Nursing Infant. PMID- 20314178 TI - The Paris Medical School. PMID- 20314180 TI - A New Salicylate. PMID- 20314179 TI - The De Quervain Clinic at Berne, Switzerland. PMID- 20314181 TI - The Habit of Sleep. PMID- 20314182 TI - Is a Coordinated Medical Course Feasible? A Suggestion. PMID- 20314183 TI - The Winnipeg Meeting. PMID- 20314184 TI - Ultra Violet Radiation in Rickets. PMID- 20314185 TI - Editorial Notes. PMID- 20314187 TI - Some Phases of Dysthyroidism. PMID- 20314186 TI - On the Relations of Heredity and Environment, of "Constitution" and "Condition", to predisposition to disease. PMID- 20314188 TI - The Study of Symptoms. PMID- 20314189 TI - The Regulatory Function of the Kidney in Nephritis. PMID- 20314190 TI - Two Cases of A Polyneuritic Affection Resembling Acrodynia met with in Young Children. PMID- 20314191 TI - Renal Tuberculosis. PMID- 20314192 TI - The Reaction of the Blood in Reference to the Regulation of Respiration and the Influence of Anaesthesia Thereon. PMID- 20314193 TI - End Results of Surgical Treatment of Diseases of the Stomach and Duodenum. PMID- 20314194 TI - Chronic Arthritis-Some Phases in its Etiology and Treatment. PMID- 20314196 TI - Studies in Radium. PMID- 20314195 TI - Bone Suppuration the Basic Cause of Renal Calculus in Twenty Cases following War Wounds. PMID- 20314198 TI - Should the Sanatorium Laboratory do Complement Fixation and Other Serum Tests as Routine Measures. PMID- 20314197 TI - Embolism of the Abdominal Aorta. PMID- 20314199 TI - Mesenteric Thrombosis-With Report of Two Cases. PMID- 20314200 TI - Bilateral Carcinoma of Breast. PMID- 20314201 TI - On Tonsillectomy; and its after Effects. PMID- 20314202 TI - The Metabolic Rate and Thyroid Disease. PMID- 20314203 TI - The Address in Medicine. PMID- 20314204 TI - Cancer of the Breast. PMID- 20314205 TI - Papers and Programmes. PMID- 20314206 TI - Iron and Ammonium Citrate. PMID- 20314208 TI - Pleurisy and Tuberculosis. PMID- 20314207 TI - Gall Bladder Problems. PMID- 20314209 TI - The Use of Circulatory Stimulants in the Care of the Sick. PMID- 20314210 TI - Functional Paraplegia (with case report). PMID- 20314211 TI - Epidemic Encephalitis-The Influence of Horse Serum in Treatment-A Preliminary Note. PMID- 20314212 TI - Medical Organization. PMID- 20314213 TI - The Relation between Physician and Druggist and Physician and Patient from the Viewpoint of Medication. PMID- 20314214 TI - The Application of the New Psychology by the Internist and General Practitioner. PMID- 20314215 TI - Pathology and Bacteriology of Empyema and Abscess of the Lung. PMID- 20314216 TI - The Value of Colostrum to the Newborn. PMID- 20314217 TI - A Report of a Medical Survey in the Wabaska District. PMID- 20314218 TI - Roentgen Ray Diagnosis of Tuberculosis of the Bones and Joints. PMID- 20314219 TI - Poisoning from the External Use of Resorcin. PMID- 20314220 TI - When to Operate on Renal Calculus. PMID- 20314221 TI - Radium Therapy (Lantern Demonstration). PMID- 20314222 TI - Retro-Caecal Abscess Rupturing into Bladder following course of Right Ureter. PMID- 20314223 TI - Abstract of Clinical Lecture on Two Cases of Tuberculosis of The Spine. PMID- 20314224 TI - An Infectious Type of Erythema Nodosum. PMID- 20314225 TI - Haemorrhagic Disease of the Newborn. PMID- 20314226 TI - Auricular Fibrillation and Quinidin. PMID- 20314227 TI - Industrial Medicine. PMID- 20314228 TI - Canadian Oto-Laryngology. PMID- 20314230 TI - Organization. PMID- 20314229 TI - A New Medical Quarterly. PMID- 20314231 TI - On the Development of Professional Initiative and Criticism-A Note from the West. PMID- 20314232 TI - Chronic Brain Injuries with Remarks Concerning the Pathology and Treatment. PMID- 20314233 TI - Surgical Therapy and Net Results in Gall Bladder Disease. PMID- 20314234 TI - A Clinical Study of Cancer of the Uterine Cervix;Summary of the Results obtained by Various Methods of Treatment. PMID- 20314235 TI - Asthma in Children. PMID- 20314236 TI - Merits of Intraperitoneal Injections in Infants. PMID- 20314237 TI - Septic Absorption in Diffuse Septic Peritonitis. PMID- 20314238 TI - Post-Operative Management. PMID- 20314239 TI - Local Anaesthesia as Applied to Operations on the Rectum and Anus. PMID- 20314240 TI - Plastic Surgery of the Head and Neck. PMID- 20314241 TI - Heliotherapy in Surgical Tuberculosis. PMID- 20314242 TI - Public Health Organization. PMID- 20314243 TI - Osteo-Arthritis. PMID- 20314244 TI - The Etiology of some Forms of Marasmus in Infancy, its Treatment by Lactic Acid Whole Milk. PMID- 20314245 TI - Lactic Acid Milk Feeding in Marasmus. PMID- 20314246 TI - The Modern Conception of Mental Disease. PMID- 20314247 TI - The Physical Education of Girls. PMID- 20314248 TI - The Influence of the Various Colours on the Mind and Emotions. PMID- 20314249 TI - The Semon Lecture at the University of London. PMID- 20314250 TI - On the Trans-Atlantic Development of Rhinolaryngology, the Semon Lecture. PMID- 20314251 TI - Non-Specific Protein Therapy. PMID- 20314252 TI - Specific Protein Therapy. PMID- 20314253 TI - The Quebec Workmen's Compensation Act-The Unoiled Cog. PMID- 20314254 TI - Mechanical Conditions favouring Infection. PMID- 20314255 TI - New Attempts to Procure Immunity to Malignant Disease in Man. PMID- 20314256 TI - Recent advances in X-Ray Treatment. PMID- 20314257 TI - Some Phases of Thyroid Disease. PMID- 20314258 TI - Some thoughts on Goitre. PMID- 20314260 TI - Exophthalmic Goitre. PMID- 20314259 TI - The Goitre Problem-From the Patient's Standpoint. PMID- 20314261 TI - Comparisons of Clinical and Radiological Findings in Lung Diagnosis. PMID- 20314263 TI - The X-Ray Findings in Empyema and Abscess of the Lung. PMID- 20314262 TI - Diagnosis of Empyema. PMID- 20314264 TI - Remarks on Deficiency Diseases. PMID- 20314265 TI - Some Observations on the Surgery of Duodenal Membrances, with a call-in-report of results of treatment. PMID- 20314266 TI - Treatment of Prostatism : The Department of Urology, Royal Victoria Hospital. PMID- 20314267 TI - Respiratory Complications after 7,000 Administrations General Anaesthetics. PMID- 20314268 TI - Focal Infection in the tonsils of adults suffering from sub-acute and chronic systemic disease : Analysis of Results of Removal in a Series of 800 Cases. PMID- 20314269 TI - Observations on some throat conditions in children. PMID- 20314270 TI - The advantages of gas inflation in obstetric and gynaecologic diagnosis with especial reference to its importance in the study of the causes of sterility. PMID- 20314271 TI - A case of chronic rhinitis, treated by Radium. PMID- 20314272 TI - A case of primary sarcoma of the Mediastinum with haemoptysis and metastases extending into the left lung and with involvement of right supraclavicular glands. PMID- 20314273 TI - Insulin and the steps taken to secure an effective preparation. PMID- 20314274 TI - The Physician in Industry. PMID- 20314276 TI - Treatment and prevention of diphtheria. PMID- 20314275 TI - The early diagnosis of pertussis. PMID- 20314277 TI - Alcohol and Industrial Efficiency. PMID- 20314278 TI - Reflex Cough in Bronchoscopic Work. PMID- 20314279 TI - EDITORIAL COMMENT. PMID- 20314280 TI - The Medical History of the War. PMID- 20314281 TI - Roman Surgery in the time of Celsus. PMID- 20314282 TI - Does the Victorian Order of Nurses have a future? PMID- 20314283 TI - When is a patient's use of primary care services unwarranted? PMID- 20314284 TI - Health economics. PMID- 20314285 TI - Canada Health Act: a plan of attack. PMID- 20314286 TI - Compulsory seat belt legislation. PMID- 20314288 TI - CMA president responds to the Act. PMID- 20314287 TI - Federal health minister tables Canada Health Act. PMID- 20314289 TI - The Provinces: Governments attacked fee increases and physicians' freedoms. PMID- 20314290 TI - The World: Cost consciousness and free enterprise were common themes. PMID- 20314291 TI - The Pharmaceutical industry: New competition and fundamental market shifts. PMID- 20314292 TI - Research: AIDS and oncogenes were two of the hot subjects. PMID- 20314293 TI - People: Dr. Phil Gold was prominent among doctors who made the news. PMID- 20314294 TI - Why scientific communications are improving. PMID- 20314295 TI - China's deterrent fee. PMID- 20314296 TI - Can academic background be detected during internship? PMID- 20314297 TI - CMAJ covers. PMID- 20314298 TI - Uniform requirements for manuscripts submitted to biomedical journals. PMID- 20314299 TI - Doctors as radio and television hosts: a new genre of health practitioner? PMID- 20314301 TI - Some reminders about RRSPs. PMID- 20314300 TI - Robert bews kerr. PMID- 20314302 TI - The vacation forecast for 1984. PMID- 20314303 TI - Specialty scientific meetings: time for critical review. PMID- 20314304 TI - Reconsidering abortion. PMID- 20314305 TI - Misleading caption. PMID- 20314306 TI - Editing the editor. PMID- 20314307 TI - CMAJ cover: showcase for physicians' talent? PMID- 20314308 TI - The auditor general and Edgar Allan Poe: two masters of horror literature. PMID- 20314309 TI - Mixing politics and science in CMAJ. PMID- 20314310 TI - Smoking for nicotine, dying from tar. PMID- 20314311 TI - Words to give up. PMID- 20314312 TI - Words to give up. PMID- 20314313 TI - Integrity of pharmacists. PMID- 20314315 TI - Scotland: sailing the Western Isles. PMID- 20314314 TI - Dr. Hugh Arnold. PMID- 20314316 TI - Medicine in the 21st century: 3. Big Sibling is watching you. PMID- 20314317 TI - Statistics in a nutshell? Never! PMID- 20314318 TI - Infant MDs? PMID- 20314319 TI - 1. Introduction. PMID- 20314320 TI - How to plan for a sabbatical. PMID- 20314321 TI - Convention cities: San Diego. PMID- 20314322 TI - Canada's rating with The Economist: overgoverned, overtaxed and underheated. PMID- 20314323 TI - Commercial malpractice insurance. PMID- 20314324 TI - Carotid Doppler evaluation in cerebrovascular disease. PMID- 20314326 TI - Ottawa using the health stick to tame its foes. PMID- 20314325 TI - Robert dickson. PMID- 20314327 TI - Pornography and violent entertainment: exposing the symptoms. PMID- 20314329 TI - The disease of not listening. PMID- 20314328 TI - So you want to practise in British Columbia? PMID- 20314330 TI - How many authors can dance on the head of an article? PMID- 20314332 TI - What the latest Liberal budget may mean to you. PMID- 20314331 TI - Certification of specialists. PMID- 20314333 TI - How much are you worth? PMID- 20314334 TI - Convention cities: Edmonton. PMID- 20314335 TI - Getting down to brass tax - and brash tactics. PMID- 20314336 TI - How to reject a manuscript. PMID- 20314337 TI - Journal publication and academic careers. PMID- 20314338 TI - Some capital "alternatives and choices". PMID- 20314339 TI - Funding of family medicine training program. PMID- 20314341 TI - Information wanted about Dr. Edward Archibald (1872-1945). PMID- 20314340 TI - Treating alcoholism can Canadian centres cope? PMID- 20314342 TI - Convention cities: Rio de Janeiro. PMID- 20314343 TI - The hazy future of interferon. PMID- 20314344 TI - Family medicine in the future organization of the health care system. PMID- 20314345 TI - To write better, write better paragraphs. PMID- 20314346 TI - Management of flail chest. PMID- 20314347 TI - Prenatal care for women planning home birth. PMID- 20314348 TI - Treatment of Jehovah's Witnesses. PMID- 20314349 TI - Home care: is it cost-effective? PMID- 20314350 TI - Costs and "benefits" of cigarette smoking. PMID- 20314351 TI - Homosexuality: an addiction? PMID- 20314352 TI - Homosexuality: an addiction? PMID- 20314353 TI - Therapeutic window for amitriptyline analgesia. PMID- 20314354 TI - Abortion denied-outcome of mothers and babies. PMID- 20314355 TI - Resuscitation: the physician-nurse relationship. PMID- 20314356 TI - Science with a smile. PMID- 20314357 TI - Staff negligence: You're legally responsible. PMID- 20314358 TI - Charles w. Fullerton. PMID- 20314359 TI - Answers to some common money and practice management questions. PMID- 20314360 TI - A national reporting program for faulty medical devices? PMID- 20314361 TI - Pap test frequency: still controversial. PMID- 20314362 TI - Task force calls for uniform prenatal records. PMID- 20314363 TI - How can family practitioners treat patients' emotions? PMID- 20314364 TI - Canadian political reporting could use more Will power. PMID- 20314365 TI - Pharmaceutical advertising in medical journals. PMID- 20314366 TI - Can treatment be compulsory? PMID- 20314368 TI - The chimera of preventive medicine. PMID- 20314367 TI - Soviet physicians against nuclear war? PMID- 20314369 TI - Diagnostic role of ultrasonography and direct cholangiography. PMID- 20314370 TI - Measles or rubella, but not rubeola. PMID- 20314371 TI - Abortion denied. PMID- 20314372 TI - Why rule out unlikely diagnoses? PMID- 20314373 TI - Australia averts national physicians' strike. PMID- 20314374 TI - Dr. Lucid's word rounds: opening a case of epilepsy. PMID- 20314375 TI - Transfer of medical records. PMID- 20314376 TI - Transfer of medical records. PMID- 20314377 TI - Health care in northern Canada. PMID- 20314378 TI - Thomas pashby. PMID- 20314379 TI - The Quebec Medical Association calls for regroupement. PMID- 20314380 TI - Convention cities: Acapulco. PMID- 20314381 TI - Commercial malpractice insurance. PMID- 20314382 TI - Teaching medical students about alcoholism. PMID- 20314383 TI - Getting down to business basics in Canadian hospitals. PMID- 20314384 TI - Jamaica's medical school: high quality on a low budget. PMID- 20314385 TI - Fixing car bodies more lucrative than mending human ones. PMID- 20314386 TI - How humour can help heal patients. PMID- 20314387 TI - What does an author's editor do? PMID- 20314388 TI - Thomas a. Watson. PMID- 20314389 TI - Manpower problems continue to plague Newfoundland. PMID- 20314390 TI - How do you measure empathy? PMID- 20314391 TI - What and how should students learn? PMID- 20314392 TI - How much does it cost to educate a physician? PMID- 20314393 TI - How does a physician choose postgraduate training? PMID- 20314394 TI - Medical education: challenges of the future. PMID- 20314395 TI - Who's who in medical education. PMID- 20314396 TI - Canada's medical schools. PMID- 20314397 TI - Reading to keep up to date. PMID- 20314398 TI - Why not write the paper on a word processor? PMID- 20314399 TI - Alcoholism: education and treatment. PMID- 20314400 TI - Air Canada's "honorary flight surgeon". PMID- 20314401 TI - Heal thyselves. PMID- 20314402 TI - How much editing does a manuscript need? PMID- 20314403 TI - Multitransplant centres. PMID- 20314404 TI - Liability insurance and locum tenens. PMID- 20314405 TI - Doctors as party politicians. PMID- 20314407 TI - "House of God" author optimistic about future. PMID- 20314406 TI - Incoming CMA president will emphasize quality of professional life. PMID- 20314408 TI - Convention cities: Paris. PMID- 20314409 TI - Is there life after the Canada Health Act? PMID- 20314410 TI - Why it's difficult to decide which new medical books to review. PMID- 20314411 TI - Torture and human rights in Chile. PMID- 20314412 TI - Torture and human rights in Chile. PMID- 20314414 TI - Dr. Joseph moriarty. PMID- 20314413 TI - Uniform requirements for manuscripts submitted to biomedical journals. PMID- 20314415 TI - India: host to World Congress of Law and Medicine in 1985. PMID- 20314417 TI - Medicine in the 21st century: 4. The hospital. PMID- 20314416 TI - Convention cities: Seattle. PMID- 20314418 TI - Internship matching. PMID- 20314420 TI - Videotapes on AIDS available. PMID- 20314419 TI - Should journals decide who gets grants? PMID- 20314421 TI - Lease inducements: the perfect deal? PMID- 20314422 TI - Compensate department heads and chiefs of staff with hard cash for administrative headaches. PMID- 20314423 TI - Proscribing habits. PMID- 20314424 TI - Dr. Lucid's word rounds: fighting germs with words. PMID- 20314425 TI - Bouquets. PMID- 20314426 TI - Word rounds: the emergency department. PMID- 20314427 TI - Birth control v. abortion. PMID- 20314428 TI - It's Greek to me. PMID- 20314429 TI - The ageing crisis is now, says CMA's task force. PMID- 20314430 TI - Convention cities: Las Vegas. PMID- 20314431 TI - UK doctors say Canadian family medicine meetings need more candour and less grandeur. PMID- 20314432 TI - The OMA and the Canada Health Act. PMID- 20314434 TI - Dr. Everett Coffin reflects on his presidency. PMID- 20314433 TI - South African doctors protest decision in Steve Biko case. PMID- 20314435 TI - Nineteen eighty-four revisited: Whatever happened to Big Brother? PMID- 20314436 TI - Scientific editing in a nutshell? At last. PMID- 20314437 TI - Closure of chest clinics in Ontario. PMID- 20314438 TI - Management of financial incompetence. PMID- 20314439 TI - Why rule out unlikely diagnoses? PMID- 20314440 TI - Homosexuality: an addiction? PMID- 20314441 TI - Air Canada's "honorary flight surgeon". PMID- 20314443 TI - Family practice training: the task force report. PMID- 20314442 TI - Marital therapy for the elderly. PMID- 20314444 TI - The pacemaker story: A cold heart spin-off. PMID- 20314445 TI - Donald I. Rice. PMID- 20314446 TI - Some thoughts on reader response. PMID- 20314447 TI - Special report on medical education. PMID- 20314448 TI - Special report on medical education. PMID- 20314449 TI - Special report on medical education. PMID- 20314450 TI - Dr. T. Alexander McPherson, president of the Canadian Medical Association, replies. PMID- 20314451 TI - Manitoba Medical Association's stand on binding arbitration. PMID- 20314452 TI - Repairing bodies: a total miscalculation. PMID- 20314453 TI - Repairing bodies: a total miscalculation. PMID- 20314454 TI - Repairing bodies: a total miscalculation. PMID- 20314455 TI - Gastric bypass surgery and nutrient deficiency. PMID- 20314456 TI - Specialists in short supply: no improvement in sight. PMID- 20314457 TI - Specialists in short supply: no improvement in sight. PMID- 20314458 TI - Task force report gets good reviews. PMID- 20314459 TI - US medical education: it's time for a change. PMID- 20314460 TI - Coping with casualties at a Papal mass. PMID- 20314461 TI - One journalist's view of Canadian doctors. PMID- 20314462 TI - Convention cities: Sydney. PMID- 20314463 TI - Oleg Livshitz: profile of an immigrant physician. PMID- 20314464 TI - Some blueprints for the Tories. PMID- 20314465 TI - Writing the right title. PMID- 20314466 TI - Heroin and pain. PMID- 20314467 TI - Malpractice suits. PMID- 20314468 TI - Medicine: a closed profession? PMID- 20314469 TI - The platform of my choice. PMID- 20314471 TI - Swimmer's lung. PMID- 20314470 TI - Doctors insist: the twain can meet. PMID- 20314472 TI - Association for handicapped physicians. PMID- 20314473 TI - Uniform requirements for manuscripts submitted to biomedical journals. PMID- 20314474 TI - Maureen roberts. PMID- 20314475 TI - Tahiti: land of Gauguin. PMID- 20314476 TI - Mr. Reagan and the new geriatric imperative. PMID- 20314477 TI - Official Soviet thinking? PMID- 20314478 TI - Head injuries and baby walkers. PMID- 20314479 TI - Head injuries and baby walkers. PMID- 20314480 TI - Unusual use of ultrasound in a paranoid patient. PMID- 20314481 TI - Unusual use of ultrasound in a paranoid patient. PMID- 20314482 TI - Halifax's Grace Maternity Hospital: a servant of the people. PMID- 20314483 TI - Convention cities: Buenos Aires. PMID- 20314484 TI - New Year resolutions: 10 words to give up in 1985. PMID- 20314485 TI - CMAJ covers tasteless and ugly? PMID- 20314486 TI - Air Canada's "honorary flight surgeon". PMID- 20314487 TI - Task force on the allocation of health care resources. PMID- 20314488 TI - Delfi symposium of psychoanalysts. PMID- 20314489 TI - "Epidemiologic report". PMID- 20314490 TI - The provinces and the profession: assessing the impact of the Canada Health Act. PMID- 20314491 TI - The provinces: fee increases decrease and extra billing is in trouble. PMID- 20314492 TI - Ethics: reproductive technology poses perplexing new problems. PMID- 20314493 TI - Research: new methods, new hearts and new findings about cholesterol. PMID- 20314494 TI - People: newsmakers of the year. PMID- 20314495 TI - Is there an ethicist in the house? PMID- 20314497 TI - Fractional doses of DPT vaccine. PMID- 20314498 TI - Cefuroxime in pediatric practice. PMID- 20314499 TI - Failure to thrive in the contented breast-fed baby. PMID- 20314500 TI - Graduates of foreign medical schools: false hope. PMID- 20314502 TI - Anonymity in medical journals. PMID- 20314501 TI - Moderate drinking: alternative treatment goal. PMID- 20314503 TI - The balance between research and medical education. PMID- 20314504 TI - Impoverished areas seeking surplus medical supplies. PMID- 20314505 TI - Marital disharmony and retirement. PMID- 20314506 TI - The continuing South African controversy. PMID- 20314507 TI - Plight of Soviet refusenik scientists. PMID- 20314508 TI - Professional misconduct. PMID- 20314510 TI - [Not Available]. PMID- 20314509 TI - Alexis carrel. PMID- 20314511 TI - Manners and medicine. PMID- 20314512 TI - The new Vienna General Hospital. PMID- 20314513 TI - Minidiplomas and special clinics. PMID- 20314514 TI - The new Vienna General Hospital. PMID- 20314515 TI - First-name basis. PMID- 20314516 TI - Private medicine in Britain. PMID- 20314517 TI - Convention cities: Heidelberg. PMID- 20314518 TI - Getting blood out of the stoned. PMID- 20314519 TI - Complication of intravenous alimentation. PMID- 20314520 TI - Cruise ship doctor Rob Thompson. PMID- 20314521 TI - Convention cities in Scotland. PMID- 20314522 TI - To cure sometimes, to relieve often, to comfort always. PMID- 20314523 TI - Is chronic pain a real condition? PMID- 20314524 TI - CMAJ covers. PMID- 20314526 TI - Question and answer: genital herpes. PMID- 20314525 TI - Question and answer: genital herpes. PMID- 20314527 TI - Training specialists in geriatrics. PMID- 20314529 TI - Information science and the general professional education of the physician. PMID- 20314528 TI - Poor need rights, not righteousness. PMID- 20314530 TI - Medicine in the 21st century: 5. Will computers replace physicians? PMID- 20314531 TI - Improving the quality of research published in CMAJ. PMID- 20314532 TI - Newborn circumcision: an economic perspective. PMID- 20314533 TI - Statistically significant or significant? PMID- 20314534 TI - Not just another government town! PMID- 20314535 TI - Air Canada's "honorary flight surgeon". PMID- 20314536 TI - Professional courtesy; first-name basis. PMID- 20314537 TI - Alzheimer's conference provokes guarded optimism. PMID- 20314538 TI - Is there room for faith in healing? PMID- 20314539 TI - Putting the art back in medicine. PMID- 20314540 TI - Apartheid: a black-and-white issue. PMID- 20314541 TI - Canadian physicians in World War II. PMID- 20314542 TI - Professional courtesy. PMID- 20314543 TI - Safety of diagnostic ultrasonography. PMID- 20314544 TI - Graduates of foreign medical schools: false hope. PMID- 20314545 TI - Death of a profession. PMID- 20314546 TI - The balance between research and medical education. PMID- 20314547 TI - First-name basis. PMID- 20314548 TI - First-name basis. PMID- 20314549 TI - First-name basis. PMID- 20314550 TI - Convention cities: San Juan. PMID- 20314551 TI - Weighing risks against benefits. PMID- 20314552 TI - Sponsorship by tobacco companies: CMA's stand. PMID- 20314553 TI - Approach to management problems. PMID- 20314554 TI - Failed midterm report: grading clinical research. PMID- 20314555 TI - Multilingual information gathering system. PMID- 20314556 TI - Dr. Lucid's word rounds. PMID- 20314557 TI - Dr. Lucid's word rounds. PMID- 20314559 TI - Legionella pneumophila serogroup 8: first isolate from a human reported in Canada. PMID- 20314558 TI - Minidiplomas and special clinics. PMID- 20314560 TI - Smallpox: posteradication surveillance. PMID- 20314562 TI - Evaluation of sponging to reduce body temperature. PMID- 20314561 TI - CMA policy positions: a message from the president. PMID- 20314563 TI - Evaluation of sponging to reduce body temperature. PMID- 20314564 TI - "Guy's Directory (Medical)". PMID- 20314565 TI - World congress on law and medicine. PMID- 20314566 TI - CAMMD: merging regulatory controls and space-age technology. PMID- 20314567 TI - Smoking and health. AB - Cigarette smoking is the leading cause of preventable death and disease in Canada, accounting for some 30 000 deaths annually. This enormous health cost to Canadians has led the Canadian Medical Association (CMA) to promote initiatives regarding smoking prevention programs in schools, legislation to prevent smoking in government buildings and controls on smoking in private buildings, particularly places of work. The CMA recommends the prohibition of all forms of tobacco advertising/promotion in Canada, including advertising in conjunction with athletic events. The CMA also supports the taxation of tobacco products at a level to discourage their purchase, with revenue earmarked for health budgets, and the association is encouraging the federal government to develop alternative crop incentives for tobacco farmers. The norm of nonsmoking is a social attitude the CMA is working toward developing in all Canadians. PMID- 20314568 TI - Poor need rights, not righteousness. PMID- 20314569 TI - Family history of allergy and skin test reactivity. PMID- 20314570 TI - The Eastman prescription: a dispensable package. PMID- 20314571 TI - The Canada Health Act "illegal"? PMID- 20314572 TI - The pastures of Health and Welfare. PMID- 20314573 TI - Who should promote health and provide preventive care? PMID- 20314574 TI - Patient dumping: the ignoble face of American medicine. PMID- 20314575 TI - The balance between research and medical education. PMID- 20314576 TI - Apartheid: a black-and-white issue. PMID- 20314577 TI - Excipients and additives. PMID- 20314578 TI - Apartheid: a black-and-white issue. PMID- 20314579 TI - Apartheid: a black-and-white issue. PMID- 20314580 TI - Strong medicine makes weak literature. PMID- 20314581 TI - Who should promote health and provide preventive care? PMID- 20314582 TI - Statistically significant or significant? PMID- 20314583 TI - Statistically significant or significant? PMID- 20314584 TI - Is there a future for homeopathy? PMID- 20314585 TI - Is there a future for homeopathy? PMID- 20314587 TI - The influence of medical journals. PMID- 20314586 TI - Diuretic-induced hypokalemia in hypertension. PMID- 20314588 TI - More on the grooves of academe. PMID- 20314589 TI - CHA delegates urged to debate fundamental health care issues. PMID- 20314590 TI - Abortion. AB - The Canadian Medical Association (CMA) recognizes that there is justification for abortion on medical and nonmedical socioeconomic grounds and that such an elective surgical procedure should be decided upon by the patient and the physician(s) concerned. Ideally, the service should be available to all women on an equitable basis across Canada. CMA has recommended the removal of all references to hospital therapeutic abortion committees as outlined in the Criminal Code of Canada. The Criminal Code would then apply only to the performance of abortion by persons other than qualified physicians or in facilities other than approved or accredited hospitals. The Canadian Medical Association is opposed to abortion on demand or its use as a birth control method, emphasizing the importance of counselling services, family planning facilities and services, and access to contraceptive information. PMID- 20314591 TI - Tumours of the Kidney. PMID- 20314593 TI - Tuberculosis of the Intestine-The Ulcerative Form, as a Phase of Pulmonary Tuberculosis. PMID- 20314592 TI - Medical Education and the Ontario Medical Association. PMID- 20314594 TI - Cancer of the Stomach. PMID- 20314595 TI - Cranial and Intracranial Injuries. PMID- 20314596 TI - Pneumonia. PMID- 20314597 TI - Hemolytic Streptococcic Infections in Children. PMID- 20314598 TI - That Baneful Cathartic after Abdominal Operations. PMID- 20314599 TI - Analysis of Sixty Cases of Gastric Anacidity Associated Mainly with Chronic Diarrhoea and Pernicious Anaemia. PMID- 20314600 TI - Acrodynia (?) A Report of Three Cases in Rural Practice. PMID- 20314601 TI - Echinococcus Cysts of the Liver in a Girl ten years old. PMID- 20314602 TI - Nitrous Oxide. PMID- 20314603 TI - Louis Pasteur. PMID- 20314604 TI - A New Factor in Bacteriolysis-The Bacteriophage. PMID- 20314605 TI - Dangerous Drugs. PMID- 20314606 TI - Goitre. PMID- 20314607 TI - On Gas Inflation in X-Ray Diagnosis. PMID- 20314608 TI - Laboratories; then and now. PMID- 20314609 TI - The Treatment of Nephritis. PMID- 20314610 TI - The Late Professor John Joseph MacKenzie, B.A., M.B. PMID- 20314611 TI - Acute Leukaemia in a Child. PMID- 20314612 TI - Some Points in the Diagnosis and Treatment of Hyperthyroidism. PMID- 20314613 TI - A Case of Primary Sarcoma of the Heart. PMID- 20314614 TI - A New Cysto-Urethroscope for Examining and Operating on any Part of the Urinary Tract by Direct-Telescope or Indirect-Periscope Methods. PMID- 20314616 TI - Industrial Medicine. PMID- 20314615 TI - Tetanus. PMID- 20314617 TI - A Case of Septic Arthritis in an Infant. PMID- 20314618 TI - Congenital Haemolytic Jaundice. PMID- 20314619 TI - Return Cases of Scarlet Fever. PMID- 20314621 TI - Ability in Children. PMID- 20314620 TI - Social Insurance. PMID- 20314622 TI - Tetany. PMID- 20314623 TI - Lead Poisoning. PMID- 20314624 TI - Septic Thrombosis; its Diagnosis and Treatment. PMID- 20314626 TI - Handbook of Child Welfare in Canada. PMID- 20314625 TI - Letchworth Village, a Model Institution for the Care of Defectives. PMID- 20314627 TI - Medicine in the Century before Harvey. PMID- 20314628 TI - The Treatment of Goitre. PMID- 20314629 TI - Cure for Sea-Sickness. PMID- 20314630 TI - The importance of the emotional or psychical nature of people in general in the practice of medicine in its widest sense. PMID- 20314631 TI - Aches and Pains of Renal Origin. PMID- 20314632 TI - A Study of One Hundred Cases of Chorea with Particular References to the Cardiac Complications. PMID- 20314633 TI - Observations on Tetany. PMID- 20314634 TI - Recent Cancer Therapy. PMID- 20314635 TI - The Control of Cancer. PMID- 20314636 TI - The Clinical Diagnosis of Smallpox and Chickenpox. PMID- 20314637 TI - Scoliosis or Lateral Curvature of the Spine. PMID- 20314638 TI - Congenital Syphilis. PMID- 20314639 TI - The Management of Discharging Ears in Children. PMID- 20314640 TI - A Note on the Phosphate Content of the Serum of Cases of Bone Tuberculosis Treated by Heliotherapy. PMID- 20314641 TI - Supplemental Feeding in Gastro-Intestinal Disturbances of the Breast Fed Infant. PMID- 20314642 TI - The Testing of Clinical Thermometers. PMID- 20314643 TI - The Limp of Childhood. PMID- 20314644 TI - Four Cases of Bronchoscopy (including two of lung abscess). PMID- 20314645 TI - Bichloride Poisoning. PMID- 20314646 TI - A Case of Diabetes Mellitus Complicating Pulmonary Tuberculosis. PMID- 20314647 TI - Hypertonic Solutions. PMID- 20314649 TI - Industrial Health Work. PMID- 20314650 TI - Recent Investigations on the Clinical Use of Arsenic. PMID- 20314648 TI - Epilepsy. PMID- 20314651 TI - The Diagnosis of Small Indefinite Masses in the Breast. PMID- 20314652 TI - On Hiccup. PMID- 20314653 TI - Rubbing Alcohol. PMID- 20314654 TI - Medical History. PMID- 20314655 TI - Mr. E. Z. Massicotte on the Physicians and Surgeons of the XVIIth and XVIIIth Centuries in the District of Montreal. PMID- 20314656 TI - Dilute Iodine Lotion in Acne. PMID- 20314657 TI - Serum Treatment of Glanders. PMID- 20314658 TI - Re Duty on Reprints. PMID- 20314659 TI - The Aims, Ambitions and Activities of the Ontario Medical Association. PMID- 20314660 TI - Problems of country Practice in New Brunswick. PMID- 20314661 TI - The Diagnosis and Treatment of Duodenal and Gastric Ulcer. PMID- 20314662 TI - The Influence of Chronic Disease of the Gall-Bladder in Producing Stomach Symptoms. PMID- 20314663 TI - Chronic Appendicits: Its Differential Diagnosis and Treatment. PMID- 20314664 TI - Visceroptosis. PMID- 20314665 TI - Pregnancy and Heart Disease. PMID- 20314666 TI - Unusual Contents of Ovarian Cysts-Report of Two Cases. PMID- 20314667 TI - Maternal Mortality. PMID- 20314668 TI - Pyelitis. PMID- 20314669 TI - The Symptoms of Acute Osteomyelitis. PMID- 20314670 TI - The New Bismuth Therapy of Syphilis. PMID- 20314672 TI - What the Profession Owes the Rural Practitioner. PMID- 20314671 TI - Epilepsy. PMID- 20314673 TI - Symptoms and Treatment of Disorders of the Digestive Tract. PMID- 20314674 TI - Tobacco Smoke. PMID- 20314675 TI - National Hospital Day. PMID- 20314676 TI - A Modern Scholar-Physician. PMID- 20314677 TI - Rudyard Kipling at the Royal College of Surgeons. PMID- 20314678 TI - Butyn. PMID- 20314679 TI - Our Immigration Policy-A Visit to Ellis Island. PMID- 20314680 TI - Motor Power in Nose and Throat Operations. PMID- 20314681 TI - Sir Thomas George Roddick. PMID- 20314682 TI - Surgical Possibilities in Traumatic Rupture of the Intestine. PMID- 20314683 TI - Rupture of the Bladder. PMID- 20314684 TI - Empyema and Abscess of the Lung. PMID- 20314685 TI - The Surgical Treatment of Cerebral Conditions Causing Intra-Cranial Pressure. PMID- 20314686 TI - Some Cerebral Manifestations of General Infection. PMID- 20314687 TI - Anaesthesia and Anaesthetics. PMID- 20314688 TI - Post-operative Tetanus. PMID- 20314689 TI - Quinidine Sulphate in Auricular Fibrillation. PMID- 20314690 TI - The Diagnostic Value of the Age Incidence of Certain Diseases in Children. PMID- 20314691 TI - Post-war Health Programme, Halifax, Nova Scotia: International Amity Exemplified. PMID- 20314692 TI - Primary Carcinoma of the Prostate, with extensive Glandular Enlargement, and Pain along course of Sciatic Nerve. PMID- 20314693 TI - The Menace of Typhoid. PMID- 20314695 TI - An Empire-wide Medical Society. PMID- 20314694 TI - On Rupture of Intestine. PMID- 20314696 TI - Industrial Medicine in Relation to Public Health. PMID- 20314697 TI - The Improvement of Provincial Relations in the Profession. PMID- 20314698 TI - Methanol, the new name for Wood Alcohol. PMID- 20314699 TI - St. Michael's Hospital Medical Bulletin. PMID- 20314700 TI - A communication from the British Medica Association. PMID- 20314701 TI - THE THERAPEUTIC ACTION OF BISMUTH IN SYPHILIS. PMID- 20314702 TI - Problems of Obstetrical Practice. PMID- 20314703 TI - The Foot-A Clinical Lecture. PMID- 20314704 TI - Dermato-Myositis. PMID- 20314705 TI - A Series of Cases of Purpura Haemorrhagica and Aplastic Anaemia due to Chronic Benzol Poisoning in a Canning Plant. PMID- 20314706 TI - Four Cases of Volvulus of the Small Intestine with Observations on the Etiology. PMID- 20314707 TI - The Evidence of Organic Heart Disease. PMID- 20314708 TI - Immunity in Tuberculosis. PMID- 20314709 TI - The Psychology of Neuroses. PMID- 20314710 TI - Antipyretic Measures. PMID- 20314712 TI - Malnutrition. PMID- 20314711 TI - Direct Measurement of Venous Pressure in Man. PMID- 20314713 TI - Modern Epidemiology. PMID- 20314715 TI - Post Operative Recurrent Appendicitis. PMID- 20314714 TI - Methylene Chloride in Anaesthesia. PMID- 20314716 TI - Aneurism of the Arch of the Aorta associated with Aneurism of the Common Carotid Artery. PMID- 20314717 TI - Gonococcal Arthritis in a New born Male Infant. PMID- 20314718 TI - Otitis Media simulating Tuberculous Meningitis. PMID- 20314719 TI - Ballantyne and the New Midwifery. PMID- 20314720 TI - Meningeal Haemorrhage of the Newly Born. PMID- 20314721 TI - The Problem of the Feebleminded. PMID- 20314722 TI - New Services in Preventive Medicine that may be Rendered by Life Insurance Companies. PMID- 20314723 TI - Sir Christopher Wren (1632-1723). PMID- 20314724 TI - The Importance of Posture in the Prevention and Treatment of Constipation. PMID- 20314725 TI - Living Sutures in the Treatment of Hernia. PMID- 20314726 TI - Insulin; Its action, its therapeutic value in diabetes, and its manufacture. PMID- 20314727 TI - Dietetic Treatment in Diabetes Mellitus. PMID- 20314728 TI - Diagnostic Notes in Obstetrics and Gynaecology. PMID- 20314729 TI - Some Aspects of the Psychoneuroses. PMID- 20314731 TI - Pellagra in Ontario with Report of Two Cases. PMID- 20314730 TI - The Use of the Wassermann Reaction in the Diagnosis of Syphilis. PMID- 20314733 TI - Diverticula of the Alimentary Canal as Demonstrated by X-Ray Examination. PMID- 20314732 TI - Some of the Factors upon which the Successful Use of Local Anaesthesia Depends. PMID- 20314734 TI - Synchronous Rupture of Bilateral Ectopics. PMID- 20314736 TI - Goitre with Hyperthyroidism. PMID- 20314735 TI - An Unusual Arrangement of the External Genitalia. PMID- 20314737 TI - The Rockefeller Foundation-Its Activities and Achievements. PMID- 20314738 TI - Our Inter-Provincial Relations. PMID- 20314739 TI - Canadian Society for the Study of the Diseases of Children. PMID- 20314740 TI - Industrial Colonies for Tuberculosis. PMID- 20314741 TI - The Septic Factor in the Three Great Plagues. PMID- 20314742 TI - President's Address. PMID- 20314743 TI - Recent Pharmacological Studies in Intestinal Peristalsis. PMID- 20314744 TI - Observations with Insulin on Department of Soldiers' Civil Re-Establishment Diabetics. PMID- 20314745 TI - Recent Advances in the Treatment of Myocarditis and Nephritis. PMID- 20314746 TI - Some Eye Symptoms in Encephalitis Lethargica. PMID- 20314747 TI - Acute Osteo-Myelitis. PMID- 20314748 TI - The Early Diagnosis and Treatment of Neurosyphilis. PMID- 20314749 TI - A Citrate Method of Blood Transfusion Devised to Minimize Post-Transfusion Reactions. PMID- 20314750 TI - Protein Hypersensitiveness and its Relation to Disease. PMID- 20314751 TI - Cyanosis. PMID- 20314752 TI - The Blood Sedimentation Test; Its History, Technique, Nature and Clinical Application. PMID- 20314754 TI - New Principles in Bacterila Immunity. PMID- 20314753 TI - The Prevention of Heart Disease. PMID- 20314755 TI - Fatigue in Industries. PMID- 20314756 TI - Animal Pathology at Cambridge. PMID- 20314757 TI - Injuries to the Forearm and Hand. PMID- 20314758 TI - Severe Industrial Injuries to the Fingers and their Treatment. PMID- 20314759 TI - Retro-pharyngeal Abscess; and Erosion of Internal Carotid Artery; with Pathological Specimen. PMID- 20314760 TI - The Pathology of Endemic Goitre. PMID- 20314761 TI - Some Unusual Feeding Cases. PMID- 20314762 TI - Address in Surgery. PMID- 20314763 TI - Some Results of Radium Treatment in Sarcoma. PMID- 20314764 TI - Medical Experiences among the Kwquithlih Indians along Discovery Passage. PMID- 20314765 TI - Industrial Medicine; its Motives and Merits. PMID- 20314766 TI - The Treatment of Bladder Tumours. PMID- 20314767 TI - Report of the Epidemic of Typhoid Fever at Mansonville, Que. PMID- 20314768 TI - Case of Streptococcus Viridans Bacteriaemia with Endocarditis and Apparent Recovery. PMID- 20314770 TI - Recent Research in the Etiology and Prevention of Rickets. PMID- 20314769 TI - Some Aspects of Experimental Pneumonia. PMID- 20314771 TI - Infantile Mortality and Sterility. PMID- 20314772 TI - Pituitrin. PMID- 20314773 TI - Venereal Disease. PMID- 20314774 TI - Help for Medical Men in Russia. PMID- 20314775 TI - Erysipelas vs. Cancer. PMID- 20314776 TI - What of the Future of Surgery. PMID- 20314777 TI - Vertigo and its Significance in General Medicine. PMID- 20314778 TI - The Effects of Ether Anaesthesia on Afferent Paths in Decerebrate Animals. PMID- 20314779 TI - Anaesthesia and Analgesia in Labour. PMID- 20314780 TI - Diagnosis of Diseases of the Stomach and Duodenum. PMID- 20314781 TI - Serous Meningitis of Otitic Origin. PMID- 20314782 TI - Some Observations on School Health Supervision in Rural and Urban Centres. PMID- 20314783 TI - Chronic Myocardial Disease. PMID- 20314784 TI - The Origin of Ammonia in the Urine. PMID- 20314785 TI - Idiopathic Menorrhagia and X-Ray Therapy. PMID- 20314786 TI - The Diagnosis of Pulmonary Tuberculosis; The Application and Interpretation of Different Tests. PMID- 20314788 TI - Canadian Physiologists at British Conventions. PMID- 20314787 TI - Quartan Malaria. PMID- 20314789 TI - The Effects of Light on the Body. PMID- 20314790 TI - Lactic Acid producing Organisms. PMID- 20314791 TI - Laboratory and Hospital. PMID- 20314792 TI - Abraham Gesner. PMID- 20314793 TI - Finances of the Association. PMID- 20314794 TI - Meeting of Ontario and Quebec Section of American College of Surgeons. PMID- 20314795 TI - Uterine Bleeding and Causes of Uterine Haemorrhage. PMID- 20314796 TI - Uterine Haemorrhage. PMID- 20314797 TI - Uterine Curettage:its Multiple Contraindications and Limited Indications. PMID- 20314798 TI - Transperitoneal Cervical Caesarian Section. PMID- 20314800 TI - Acute Intestinal Intoxication. PMID- 20314799 TI - Acute Intestinal Intoxication in Infants : An Analysis of Seventy-five Cases Treated in the Hospital for Sick Children, Toronto, During the Summer of 1922. PMID- 20314801 TI - Chronic Sinusitis in Children. PMID- 20314802 TI - Heart Disease in Children. PMID- 20314803 TI - Clinical and Bio-Chemical study of a case of muscular Weakness in an Infant. PMID- 20314804 TI - Biopsies and the Completion of certain Surgical Procedures. PMID- 20314805 TI - The Present State of our Knowledge Regarding Rejuvenation. PMID- 20314806 TI - Comparison of Quantitative Tests for Sugar in Urine. PMID- 20314807 TI - Reports of Two Unusual Cases in Surgical Practice. PMID- 20314808 TI - Proposed Banting Medical Research Foundation. PMID- 20314809 TI - The Etiology and Treatment of Shock. PMID- 20314810 TI - On Excessive Magnification of Sport in a University. PMID- 20314812 TI - The Frequency of Chlorosis. PMID- 20314811 TI - Abram's Theory. PMID- 20314813 TI - Water Intoxication. PMID- 20314814 TI - British Journal of Anaesthesia. PMID- 20314815 TI - Charles Gabriel Pravaz. PMID- 20314816 TI - Sir Charles Bell. PMID- 20314817 TI - Pleural Infections. PMID- 20314818 TI - Tuberculous Cervical Adenitis in Children. PMID- 20314819 TI - Some Uses of Radium in Diseases of Women. PMID- 20314820 TI - The Obstetrical Causes and Prevention of Stillbirth and Early Infant Mortality. PMID- 20314822 TI - Treatment and General Management of Eczema in Infants in Private Practice. PMID- 20314821 TI - A Case of Severe Delayed Anaphylaxis. PMID- 20314823 TI - Hereditary Syphilis. PMID- 20314824 TI - The Clinical View of D'Espine's Sign. PMID- 20314825 TI - FEEDING PROBLEMS OF OLDER CHILDREN. PMID- 20314826 TI - Suggestion, Ancient and Modern. PMID- 20314827 TI - Conditions in Canada in the Combat against Tuberculosis: An address delivered before the Mississippi Valley League of Anti-Tuberculosis Societies at their annual banquet, Evansville, Ind., Oct. 9th, 1923. PMID- 20314828 TI - The Ocular Malingerer. PMID- 20314829 TI - Injuries to the Eyes from Broken Glasses. PMID- 20314830 TI - Multiple Myeloma. PMID- 20314831 TI - Hypernephroma of the Kidney, associated with repeated attacks of Haematuria and Metastases in the Bones. PMID- 20314833 TI - Forecast for the Coming Year. PMID- 20314832 TI - Perirenal Insufflation. PMID- 20314834 TI - The Tuberculous Man at Home. PMID- 20314835 TI - The Influence of the Weather on Influenza. PMID- 20314836 TI - On Dreams. PMID- 20314837 TI - A Useful Diet Table. PMID- 20314839 TI - Magic and medicine. PMID- 20314838 TI - Abraham Gesner. PMID- 20314841 TI - Civil Service Commission Salaries. PMID- 20314840 TI - The International Congress of Surgeons-Discussion on the Surgery of the Endocrine Glands. PMID- 20314842 TI - The Treatment of Intestinal Obstruction. PMID- 20314843 TI - Symposium on Differential Diagnosis of Abdominal Lesions. PMID- 20314844 TI - Physiology and Clinical Medicine. PMID- 20314845 TI - Renal and splenic Lesions as Factors in Upper Abdominal Disease. PMID- 20314846 TI - Discussion on Renal and Splenic Lesions. PMID- 20314847 TI - The Acute Abdomen : Symptomatology and Pathology. PMID- 20314849 TI - Insulin Treatment in Diabetes in Children. PMID- 20314848 TI - A Formula for Expressing Balance in the Diabetic Organism: A Preliminary Communication. PMID- 20314850 TI - Haematuria-Its Significance. PMID- 20314851 TI - Two Cases of Infestation of the Intestine with Larvae of Species of Fannia. PMID- 20314852 TI - Report on an Outbreak of Alastrim in Antigua, B.W.I. PMID- 20314853 TI - Suction Apparatus for Removing Mucus from the New-Born. PMID- 20314854 TI - The Operation of Cartilage-Cranioplasty. PMID- 20314855 TI - Tuberculous Ulceration of the Intestines. PMID- 20314857 TI - Our Canadian Medical Association and a National Spirit. PMID- 20314856 TI - Direct Transfusion for Acute Phthisis Following the Puerperium. PMID- 20314858 TI - Tonsillar Innfection and Systemic Disease. PMID- 20314859 TI - The X-Ray Treatment of Diseased Tonsils. PMID- 20314860 TI - The Social Aspects of Mental Defect. PMID- 20314862 TI - The Centenary of the Lancet. PMID- 20314861 TI - Report of the Committee on Inter-Provincial Relations for the Year 1922-1923. PMID- 20314863 TI - Industrial Intoxication. PMID- 20314864 TI - Notes of a Visit to Some of the Anatomical Schools and Surgical Clinics of Europe in 1887. PMID- 20314865 TI - Retained Placenta; Expectant Treatment Successful. PMID- 20314866 TI - Referred Pain in Aneurism. PMID- 20314867 TI - The Use and Abuse of Endocrinology. PMID- 20314868 TI - Suction Drainage in Acute Empyaema. PMID- 20314869 TI - Concerning the Definition and Classification of Anaemias. PMID- 20314870 TI - Pyelitis in Children. PMID- 20314872 TI - Practical Application of Insulin in Diabetes. PMID- 20314871 TI - My Experience with the Caesarian Operation. PMID- 20314874 TI - Thrombosis and Embolism. PMID- 20314873 TI - The Association of Pulmonary and Bone and Joint Tuberculosis. PMID- 20314875 TI - The Treatment of Exophthalmic Goitre with Report on a Series of Cases Treated. PMID- 20314877 TI - X-Ray Treatment of Pertussis. PMID- 20314876 TI - Sterility in the Male. PMID- 20314878 TI - Toxaemia of Pregnancy (Hepatic Type). PMID- 20314879 TI - A Case of the Adult Type of Tuberculosis in Childhood, Complicated by Tuberculous Bronchopneumonia. PMID- 20314880 TI - Cysticercus of Taenia Solium in Human Brain. PMID- 20314882 TI - The Society of Friends of Medical Progress. PMID- 20314881 TI - A Case of Erythro-Melalgia. PMID- 20314883 TI - Recent Researches on Cancer. PMID- 20314884 TI - The Problem of Cardiac Disease. PMID- 20314886 TI - The Lady Byng of Vimy Fund for Mental Hygiene. PMID- 20314885 TI - The Causes of a Declining Tuberculosis Death Rate. PMID- 20314887 TI - Physiological Standardization and its Limitations. PMID- 20314888 TI - Editorial Comments. PMID- 20314889 TI - Notes of a Visit to some of the Anatomical Schools and Surgical Clinics of Europe in 1887, (Part II). PMID- 20314890 TI - A Clinical Lecture on Chronic Arthritis. PMID- 20314891 TI - The Effects of Stagnation in the Ascending Colon. PMID- 20314892 TI - An Address at the Opening of the Woman's Clinic, Johns Hopkins Hospital, Baltimore. PMID- 20314893 TI - An Address, in abstract, on the Psychoneuroses. PMID- 20314894 TI - The Surgical Treatment of Bronchiectasis. PMID- 20314895 TI - Combined Use of Quinidine and Digitalis in Chronic Auricular Fibrillation and Flutter. PMID- 20314896 TI - The Portals of Entry of Chronic Metastatic Infections. PMID- 20314897 TI - Intestinal Bands and Intestinal Adhesions-Differential Diagnosis and Treatment-A Plea for More Accurate Nomenclature. PMID- 20314898 TI - A Study of the Bacteriology of the Norma and Inflamed Conjunctiva with Special Reference to the Presence of the Streptococcus and Pneumococcus. PMID- 20314899 TI - The Use of Lugol's Solution in the Treatment of Exophthalmic Goitre. PMID- 20314900 TI - A Comparison of the Kahn Test with the Wassermann Test. PMID- 20314901 TI - The Internist's Responsibility: Certain Factors Involved in the Selection and Classification of Surgical Risks. PMID- 20314902 TI - Accessory Nasal Sinus Infection. PMID- 20314903 TI - Uncinate Fits. PMID- 20314904 TI - Reduction En Masse of a Strangulated Inguinal Hernia. PMID- 20314905 TI - Thoracic Surgery. PMID- 20314907 TI - Bronchoscopy. PMID- 20314906 TI - Recent Advances in Thoracic Surgery. PMID- 20314908 TI - The Mental Hospital and Its Service. PMID- 20314910 TI - Prognosis in Angina Pectoris. PMID- 20314909 TI - The Value of Psychology. PMID- 20314911 TI - The Therapeutic Use of Oxygen. PMID- 20314912 TI - Post-Holiday Lassitude. PMID- 20314913 TI - The Lay Conference of the Ontario Medical Association. PMID- 20314914 TI - A New Remedy, Bayer 205. PMID- 20314915 TI - Prevention of Heart Disease. PMID- 20314916 TI - Cardiac Pain. PMID- 20314917 TI - The Toxaemia of Severe Superficial Burns. PMID- 20314918 TI - Carbon Monoxide Asphyxiation from Motor Exhaust. PMID- 20314920 TI - Enlarged Tonsils and Adenoids. PMID- 20314919 TI - Fixation of Radium Emanations. PMID- 20314921 TI - Early Adventures with Chloroform in Nova Scotia. PMID- 20314923 TI - The Lay Conference with Representatives of the Ontario Medical Association. PMID- 20314922 TI - The Early Story of Vaccination on this Continent. PMID- 20314924 TI - An Address on Surgeon and Student. PMID- 20314925 TI - Endemic Goitre. PMID- 20314926 TI - The Operation of Caeco-Colo-Plico-Pexy. PMID- 20314927 TI - A Preliminary Report on the Bacteriology of Ureteral Cultures. PMID- 20314928 TI - The Incidence of Diabetes Mellitus in Diseases of the Gall Bladder and its Passages (Biometrical Study). PMID- 20314929 TI - Pre and Post-Operative Purgation. PMID- 20314930 TI - On Hyperthyroidism. PMID- 20314931 TI - A Case of Henoch's Purpura. PMID- 20314932 TI - Dysmenorrhoea as a Result of Disturbance of Function of the Endocrine Glands. PMID- 20314933 TI - Kidney Disease from the View Point of the Biochemist. PMID- 20314934 TI - A Case of Persistent Aciduric Intestinal Flora in Man. PMID- 20314935 TI - Lessons from the Windsor Outbreak of Smallpox: From the Provincial Board of Health, Ontario. PMID- 20314936 TI - Two Cases of Arthritis Simulating Acute Rheumatic Fever Complicating Pneumonia. PMID- 20314937 TI - Fracture of the Clavicle, Acromion Process and Surgical Neck of the Scapula. PMID- 20314938 TI - Notes on the Clinical Signs of Infantile Rickets as Observed in Vienna. PMID- 20314939 TI - The Treatment of General Paralysis by Malaria. PMID- 20314941 TI - Alcoholic Intoxication in Automobile Drivers. PMID- 20314940 TI - The Results Obtained from Testicular Grafts. PMID- 20314943 TI - On the Value of Massage and Remedial Gymnastics. PMID- 20314942 TI - Bulletin of National Committee for Mental Hygiene. PMID- 20314945 TI - The British Empire Cancer Campaign. PMID- 20314944 TI - Medical Insurance Examination Fees. PMID- 20314947 TI - The Effect of Opium in Cardiac Dyspnoea. PMID- 20314946 TI - Dangerous Drugs. PMID- 20314948 TI - Treatment of Dysmenorrhoea. PMID- 20314949 TI - Dirty Paper Money. PMID- 20314950 TI - The Danger of Frozen Toxin-Antitoxin. PMID- 20314951 TI - Infection by Public Telephones. PMID- 20314952 TI - Cancer Number of the Canadian Practitioner. PMID- 20314953 TI - Georges Linossier. PMID- 20314954 TI - Charles White (1728-1813). PMID- 20314955 TI - The Surgical Treatment of Bronchiectasis. PMID- 20314956 TI - Banting Research Foundation. PMID- 20314957 TI - Surgery and Surgeons. PMID- 20314958 TI - Official Delegates from the British Medical Association. PMID- 20314959 TI - The Quebec Section of the American College of Surgeons. PMID- 20314960 TI - Problems in the Metabolism of Diabetes. PMID- 20314962 TI - Management of Toxaemia in the Later Months of Pregnancy. PMID- 20314961 TI - Some Indications for the Radical Mastoid Operation in Otitis Media Purulenta Chronica. PMID- 20314963 TI - Glycosuria in Pregnancy. PMID- 20314964 TI - The Progress in Mental Hygiene in Manitoba. PMID- 20314965 TI - Indications for Tonsillectomy with a Criticism of the Operation. PMID- 20314967 TI - Blood Transfusion-Factors Frequently Overlooked. PMID- 20314966 TI - Remarks on the Treatment of Fractures of the Leg. PMID- 20314968 TI - Parotid Calculi. PMID- 20314969 TI - Naevi and their Treatment by Radium. PMID- 20314970 TI - Recent Advances in the Control of Diphtheria. PMID- 20314971 TI - The Standardization and Value of Thyroid Preparations. PMID- 20314973 TI - Enuresis. PMID- 20314972 TI - The Relation Between the Width of the Pupil and the Carbon Dioxide Content of the Blood. PMID- 20314974 TI - Dehydration Anaemia. PMID- 20314975 TI - Amplified Heart Sounds for Auditorium Demonstration. PMID- 20314976 TI - Acute Boracic Acid Poisoning (Fatal). PMID- 20314978 TI - Metabolism in Diabetes. PMID- 20314977 TI - The Etiology of Scarlet Fever. PMID- 20314980 TI - Malignant Disease in Egypt. PMID- 20314979 TI - Leukocytic Trephones. PMID- 20314981 TI - The Acid Base Balance of the Blood. PMID- 20314982 TI - Mental Defect in Early Childhood. PMID- 20314983 TI - Chlorine Therapeusis. PMID- 20314985 TI - Death Rate from Diabetes. PMID- 20314984 TI - The Financial Page. PMID- 20314986 TI - Penal Institutions in Nova Scotia. PMID- 20314987 TI - Co-operation between Alberta Medical Association and College of Physicians and Surgeons. PMID- 20314988 TI - The Conquest of Pellagra. PMID- 20314989 TI - Diabetes a Century Ago. PMID- 20314990 TI - Intra-Bronchial Pressure. PMID- 20314991 TI - Prevention of Goitre. PMID- 20314992 TI - The Manual Reduction of Strangulated Hernia (Taxis). PMID- 20314993 TI - An Address on Some Effects of Temperature on the Blood and Circulation. PMID- 20314994 TI - An Address on the Use of Immune Sera. PMID- 20314995 TI - Clinical Lecture on Lead Neuropathy. PMID- 20314996 TI - The Influence of Infection upon the Reaction of the Diabetic to Insulin Treatment. PMID- 20314997 TI - The Problem of the Right Iliac Fossa. PMID- 20314998 TI - Some Notes on the Operation for Appendicitis. PMID- 20314999 TI - The Modern Therapy of Syphilis. PMID- 20315000 TI - Prophylaxis in Obstetrics, with Special Reference to the Value and Importance of Pre-Natal Care. PMID- 20315001 TI - A Case of Galactorrhoea. PMID- 20315002 TI - Conservatism in the Treatment of Chronic Accessory Nasal Sinus Disease with a Report of an Illustrative Case. PMID- 20315003 TI - Fixed Principles in the Feeding of Infants. PMID- 20315004 TI - Community Psychosis. PMID- 20315005 TI - Child Guidance Clinics. PMID- 20315006 TI - The Use of Phenoltetrachlorphthalein as a Test of Liver Function. PMID- 20315007 TI - A Case of Thrombo-Angeitis Obliterans. PMID- 20315008 TI - A Mixed Cell Sarcoma of the Kidney in a Child Eleven Months Old. PMID- 20315009 TI - Hydrocephalus Complicating Intracranial Haemorrhage in a New-Born Infant. PMID- 20315011 TI - Capillary Pulsation. PMID- 20315010 TI - Vitamins. PMID- 20315012 TI - On the Action of Radium and X-Rays. PMID- 20315013 TI - The Effect on the Kidney of the Modern Treatment for Syphilis. PMID- 20315014 TI - Influence of Alcohol on the Vitality of the Race. PMID- 20315015 TI - Rest Pauses in Industry. PMID- 20315016 TI - Should We have Faculties of Public Health. PMID- 20315017 TI - Standards of Nutrition. PMID- 20315018 TI - An International Health Organization and the League of Nations. PMID- 20315019 TI - Psychic Flurries. PMID- 20315020 TI - A Lister Memorial. PMID- 20315021 TI - Discussion on Vertigo. PMID- 20315022 TI - Sound Teeth. PMID- 20315023 TI - The Venereal Diseases Grant. PMID- 20315024 TI - Canadian Medical Association. PMID- 20315025 TI - An Address before the Canadian Tuberculosis Association. PMID- 20315027 TI - Technique and Results of a Concentration Method of Sputum Examination. PMID- 20315026 TI - An Improved Method of Lung Percussion. PMID- 20315028 TI - Radiographic Findings Diagnostic of Pulmonary Tuberculosis. PMID- 20315029 TI - Conclusions from Repeated Physical and X-Ray Examination of Ex-Service Men. PMID- 20315030 TI - Symptoms of Upper Respiratory Tract Disease Simulating Tuberculosis. PMID- 20315031 TI - Observations on Some of the Commoner Septic Conditions of the Chest: Their Diagnosis and Treatment. PMID- 20315032 TI - The Differentiation and Treatment of Lung Abscess by Exploratory Pulmonary Puncture and Bismuth Injection. PMID- 20315033 TI - Non-Tuberculous Pulmonary Diseases. PMID- 20315034 TI - Syphilis of the Lung. PMID- 20315035 TI - Over-Diagnosis of Pulmonary Tuberculosis. PMID- 20315036 TI - The Relation of Disordered Heart Action to the Development of Tuberculosis-A Review of the History of a Series of five hundred Cases. PMID- 20315037 TI - A Preliminary Report upon the Clinical and Experimental Use of Dreyer's Tuberculo Antigen. PMID- 20315038 TI - Complications Met in Sanatorium Practice. PMID- 20315039 TI - The Neurasthenic Reaction. PMID- 20315040 TI - Report of a Case of Addison's Disease Treated with Benefit by a Suprarenal Transplant. PMID- 20315041 TI - Bullet Wound of Abdomen, Liver and Lung; Recovery. PMID- 20315042 TI - A Smallpox Epidemic. PMID- 20315043 TI - A Review of the Recent Literature on Subacute Bacterial Endocarditis. PMID- 20315045 TI - The Recent Conference on Tuberculosis. PMID- 20315044 TI - The Canadian Tuberculosis Association. PMID- 20315047 TI - "What of Rest in Tuberculosis?". PMID- 20315046 TI - Results Obtained. PMID- 20315048 TI - Efforts to Control the Spread of Tuberculosis in Great Britain. PMID- 20315049 TI - Mental Hygiene Research Fund. PMID- 20315050 TI - University Clinics and the Rockefeller Gift. PMID- 20315051 TI - The Lister Memorial Fund. PMID- 20315052 TI - Investments. PMID- 20315053 TI - An Address on Clinical and Laboratory Methods of Diagnosis. PMID- 20315054 TI - Tuberculosis of the Larynx-Its Diagnosis and Treatment: A Plea for Closer Co operation Between the Physician and Laryngologist. PMID- 20315055 TI - Roentgen-Ray Sickness and Chloride Retention. PMID- 20315056 TI - Some Anatomical Points Relative to Infections of the Hand. PMID- 20315057 TI - Conservation in Treatment of Hand Injuries. PMID- 20315058 TI - The Epidemic of Virulent Smallpox in Windsor and the Vicinity. PMID- 20315060 TI - Treatment of Abortion. PMID- 20315059 TI - A Few Remarks on Prophylaxis in Obstetrics. PMID- 20315061 TI - Anaesthesia in Obstetrics. PMID- 20315062 TI - Some Conclusions after a Symposium in Obstetrics. PMID- 20315063 TI - Intracardiac Adrenalin in Asphyxia Neonatorum. PMID- 20315064 TI - Modern Tendencies in Infant Feeding. PMID- 20315065 TI - The Use of Acid Milk Mixtures in Infant Feeding. PMID- 20315066 TI - Certain Factors in the Diagnosis of Syphilis Unrecognized in the Earlier Years of the Infection. PMID- 20315067 TI - Tryparsamide in General Paresis and Other Forms of Neurosyphilis. PMID- 20315068 TI - The Management of the Neurosyphilitic. PMID- 20315069 TI - The Silhouette Radiograph as an Aid to Clinical Diagnosis. PMID- 20315070 TI - A Fatal Case of Diabetes Mellitus Complicated by Infection. PMID- 20315071 TI - A Case of Cerebral Tumour. PMID- 20315072 TI - Rupture of the Right Rectus Simulating Appendicitis. PMID- 20315073 TI - Rat Bite Fever. PMID- 20315074 TI - Rheumatic Fever and Endocarditis. PMID- 20315076 TI - The Result of Tonsillectomy on the Health of Children. PMID- 20315075 TI - The Causation and Significance of Fever. PMID- 20315077 TI - Regeneration of Cells of Pancreas under Use of Insulin. PMID- 20315078 TI - The Discovery of the Origin of Foot and Mouth Disease. PMID- 20315080 TI - Contagious Diseases of Childhood. PMID- 20315079 TI - The Ammonia of the Urine. PMID- 20315081 TI - Are Bacteria Animals or Plants? PMID- 20315082 TI - The Work of the Rockefeller Foundation for 1923. PMID- 20315083 TI - The Use of Sodium Chloride in the Treatment of Intestinal Obstruction. PMID- 20315084 TI - The Value of Condensed Cows' Milk in the Tropics. PMID- 20315085 TI - Comparative Pathology. PMID- 20315086 TI - Method of Transmission of the Plague Bacillus to Man. PMID- 20315087 TI - Farewell Letter from English Delegates. PMID- 20315088 TI - An Address on the Diagnosis of a Healthy Heart. PMID- 20315089 TI - Views on Prostatectomy. PMID- 20315090 TI - Effect of Popular Gynaecological Procedures on the Future Child-Bearing of Women. PMID- 20315091 TI - Some Aspects of Post-Operative Treatment in Gynaecologic and Abdominal Surgery. PMID- 20315092 TI - The Treatment of Diabetes Mellitus. PMID- 20315093 TI - Some Recent Advances in Endocrinology. PMID- 20315094 TI - The Use and Abuse of Iodine in the Treatment of Goitre. PMID- 20315095 TI - Leprosy in Canada. PMID- 20315096 TI - The Interpretation of Symptoms in Acute Abdominal Disease. PMID- 20315097 TI - Some Clinical Aspects of Unsuspected Hypertoxic Appendicitis. PMID- 20315098 TI - Acute Perforation of the Stomach or Duodenum. PMID- 20315100 TI - Hypertension and Its Relationship to the Functional Activities of the Vessels. PMID- 20315099 TI - Anaesthesia in Acute Abdominal Operations. PMID- 20315101 TI - The Role of the Bone Marrow in Primary Blood Diseases. PMID- 20315102 TI - Some Types of Non-Tuberculous Pulmonary Infection. PMID- 20315103 TI - Bacteriology of Pulmonary Infections. PMID- 20315104 TI - Remarks on Dr. Gordon's Paper. PMID- 20315105 TI - Aneurism of the Arch of the Aorta. PMID- 20315106 TI - Chronic Suppurative Otitis-Media with a Fistula of the External Semi-Circular Canal. PMID- 20315107 TI - A Horn on the Scalp. PMID- 20315108 TI - Intravenous Use of Mercurochrome in an Infant aged Three Weeks. PMID- 20315109 TI - Idiopathic Aplastic Anaemia in a Child. PMID- 20315110 TI - Tetanus. PMID- 20315111 TI - Epidemic Encephalitis (Encephalitis Lethargica). PMID- 20315113 TI - Crime and Its Punishment. PMID- 20315112 TI - Vitamines, Endocrines and Cancer. PMID- 20315114 TI - Voluntary Hospitals. PMID- 20315115 TI - Alcohol and the Duration of Life. PMID- 20315116 TI - On the Diagnosis of Cancer of the Stomach. PMID- 20315117 TI - Tularaemia. PMID- 20315118 TI - Commercialism in the Profession. PMID- 20315119 TI - An Efficient Vaccine for Rabies. PMID- 20315120 TI - The Effects on Public Health of the Pollution of Coast, Lake and River Waters by Oil-Burning Steamers. PMID- 20315121 TI - On the Intermarriage of Cousins. PMID- 20315122 TI - Congress Interferes with Physicians' Prescriptions. PMID- 20315123 TI - School of Hygiene in the University of Toronto. PMID- 20315124 TI - Motor Emblems. PMID- 20315125 TI - Leprosy in Canada. PMID- 20315126 TI - A New Departure for the London Lancet. PMID- 20315127 TI - The History of Plague. PMID- 20315129 TI - A Reserve Fund. PMID- 20315128 TI - American Medical Association. PMID- 20315130 TI - Investments. PMID- 20315131 TI - Investments. PMID- 20315133 TI - Haematuria. PMID- 20315134 TI - Tuberculosis and Calcification of Prostate: Report of a Case. PMID- 20315132 TI - An Address on Obstetrics During the Past Twenty-five Years. PMID- 20315136 TI - Some Points in Treatment of Breast Cancer. PMID- 20315135 TI - Observations on the Urea Concentration Factor in the Estimation of Renal Efficiency. PMID- 20315137 TI - Surgical Treatment of Chronic Lesions of the Breast. PMID- 20315138 TI - Some Aspects of the Pathology of Chronic Breast Lesions. PMID- 20315139 TI - Anaesthesia in Breast Operations. PMID- 20315140 TI - Silicosis in Ontario Gold Miners. PMID- 20315141 TI - Empyema. PMID- 20315142 TI - Empyema-Acute and Chronic. PMID- 20315143 TI - Dietetics in the Treatment of the Diabetic Patient. PMID- 20315144 TI - Renal Glycosuria in an Infant Twenty Months of Age. PMID- 20315145 TI - Some Points in the Value of X-Rays for Prognosis in Pulmonary Tuberculosis. PMID- 20315146 TI - Pneumococcal Peritonitis. PMID- 20315147 TI - Vitamin A and Its Variations in Cod Liver Oil. PMID- 20315148 TI - Medullary Hypernephroma with Cranial Metastases. PMID- 20315149 TI - Varicose Aneurysm-Right Axillary Vessels. PMID- 20315150 TI - Report of a Case of Cutaneous Myiasis in an Infant. Wohlfahrtia Vigil (Walker) Infection. PMID- 20315151 TI - Foreign Bodies in the Bronchi: A Report of Two Cases. PMID- 20315152 TI - A Case of Early Dementia Praecox. PMID- 20315153 TI - Congenital Deficiency of Small Intestine. PMID- 20315154 TI - Some Recent Advances in the Diagnosis of Compression of the Cord. PMID- 20315155 TI - On Chemotherapy. PMID- 20315157 TI - On Crime and Punishment. PMID- 20315156 TI - The Parathyroids, Guanidines and Tetany. PMID- 20315158 TI - Tryparsamide in Late Neurosyphilis. PMID- 20315159 TI - The Influence of Diet on the Development of the Dental Structures. PMID- 20315160 TI - Some Dangers of Theory in Medicine. PMID- 20315162 TI - The Journal to Canadian Medical Missionaries. PMID- 20315161 TI - About Telling the Truth. PMID- 20315163 TI - Sir William Osler Memorial Volume. PMID- 20315164 TI - Thomas Sydenham (1624-1689). PMID- 20315165 TI - SUPPLEMENT. PMID- 20315167 TI - An Address on the Prompt Diagnosis of Pulmonary Tuberculosis. PMID- 20315166 TI - An Address Some Thoughts-New and Old-on Arteriosclerosis. PMID- 20315169 TI - A Statistical Report Concerning the Value of the Study of the Blood Chemistry in the Acute Abdomen. PMID- 20315168 TI - The Treatment of Obesity. PMID- 20315170 TI - The Use of Calcium Chloride in Arterial Hypertension. PMID- 20315171 TI - The Clinical Significance of Vertigo. PMID- 20315172 TI - Some Aspects of Nasal Accessory Sinus Disease. PMID- 20315173 TI - Thyroid Preparations in the Treatment of the Stokes-Adams' Syndrome. PMID- 20315174 TI - X-Ray Technique in Examination of the Chest. PMID- 20315175 TI - Bacteriology of Scarlet Fever. PMID- 20315176 TI - The Clinical Aspect of Scarlet Fever. PMID- 20315177 TI - Heart Complications in Scarlet Fever. PMID- 20315178 TI - Ear, Nose and Throat Complications of Scarlet Fever. PMID- 20315179 TI - Secondary Pneumonia; Some Therapeutic Considerations. PMID- 20315180 TI - The Parturient Perineum-Its Management. PMID- 20315181 TI - The Study of Fungi in Diseases of the Skin. PMID- 20315182 TI - The Treatment of Chronic Ulcers of the Leg. PMID- 20315183 TI - Small Ulcers of the Tongue. PMID- 20315184 TI - A Case for Diagnosis. PMID- 20315185 TI - Foreign Bodies in the Stomach. PMID- 20315186 TI - Severe Toxaemia Following Bee Stings. PMID- 20315187 TI - Vagitus Uterinus. PMID- 20315188 TI - Recent Work on Scarlet Fever. PMID- 20315189 TI - The Medical Treatment of Hydrocephalus. PMID- 20315190 TI - On Resuscitation after Failure of Respiration. PMID- 20315191 TI - The Prone Pressure (Schafer) Method of Resuscitation. PMID- 20315192 TI - On the Prevention of Respiratory Failure. PMID- 20315193 TI - Epidemic Diaphragmatic Pleurodynia "Devil's Grip". PMID- 20315194 TI - The Etiology of Rickets. PMID- 20315195 TI - Anhydraemia in Young Infants. PMID- 20315197 TI - Studies of Anaemia in Infancy and Childhood. PMID- 20315196 TI - A New Revision of the United States Pharmacopoeia. PMID- 20315198 TI - Rapid Reproduction of Rats. PMID- 20315199 TI - Periodical Medical Examinations. PMID- 20315200 TI - On the Origin of Bilirubin. PMID- 20315201 TI - Investments. PMID- 20315202 TI - Presidential Address on the Neglected Side of Medicine. PMID- 20315204 TI - Compound Fractures. PMID- 20315203 TI - Anatomical Types and their Relationship to Disease. PMID- 20315205 TI - Primary Ulcerative Colitis. PMID- 20315206 TI - Cerebral Haemorrhage in the Newborn. PMID- 20315207 TI - Erysipelas Successfully cured by Subcutaneous Injection of Cows' Milk. PMID- 20315208 TI - Destruction and Removal of Accessible Neoplastic Diseases by Endothermy. PMID- 20315209 TI - Remarks on the Treatment of Chronic Peptic Ulcer with a Report of Three Illustrative Cases. PMID- 20315210 TI - Chronic Myocarditis: A Clinical Review. PMID- 20315211 TI - Chronic Infective Arthritis. PMID- 20315212 TI - Industrial Ocular Injuries. PMID- 20315213 TI - How to Prepare and to Deliver a Paper to a Medical society. PMID- 20315215 TI - A Case of Papilloma of the Sigmoid. PMID- 20315214 TI - A Case of Tertian Malarial Fever Following an Operation for Appendicitis. PMID- 20315216 TI - Picric Acid Poisoning. PMID- 20315217 TI - An Unusual Case of Ringworm in an Adult (Due to Trichophyton Gypseum). PMID- 20315218 TI - Tuberculosis of the Peritoneal and Pleural Sacs Treated by Alpine Lamp. PMID- 20315219 TI - A NEW JOURNAL. PMID- 20315220 TI - Recent Work on the Capillaries. PMID- 20315221 TI - Success in Medicine. PMID- 20315222 TI - Dysmenorrhoea. PMID- 20315223 TI - Pneumonic Plague. PMID- 20315224 TI - The Importance of the Mineral Elements in the Diet. PMID- 20315225 TI - The Physician's Education. PMID- 20315227 TI - Myelinogeny as Applied to the Study of Behaviour. PMID- 20315226 TI - The Swing of the Pendulum. PMID- 20315228 TI - The Doctrine of Malthus. PMID- 20315229 TI - Necessity for Education of the Public in the Details of Personal Hygiene. PMID- 20315230 TI - The Success of Academic Institutions. PMID- 20315232 TI - Professor Pavlov. PMID- 20315231 TI - The Etiology of Fatigue. PMID- 20315233 TI - The Surgical Treatment of Angina Pectoris. PMID- 20315234 TI - The Value of Hexamine as an Antiseptic in Systemic Infections. PMID- 20315235 TI - The Treatment of Scurvy. PMID- 20315236 TI - OBITURAY. PMID- 20315237 TI - Investments. PMID- 20315238 TI - Foreword. PMID- 20315239 TI - Annual Fee. PMID- 20315240 TI - Lupus Erythematosus and Its Treatment by Radium. PMID- 20315241 TI - An Address on the Treatment of Chronic Heart Failure. PMID- 20315242 TI - An Address on the Cause of Dyspnoea. PMID- 20315243 TI - Recent Advances in our Knowledge of Scarlet Fever. PMID- 20315244 TI - Pernicious Anaemia: Etiological Considerations, with Report of a Series of Experiments. PMID- 20315245 TI - The Cause of the Matutinal Alkaline Tide of the Urine. PMID- 20315246 TI - Autotransfusion. PMID- 20315247 TI - A Case of Hypernephroma Associated with Thyroid Hyperactivity. PMID- 20315248 TI - Pyelitis in Infancy and Childhood. PMID- 20315249 TI - A Few Comments on Gastro-Intestinal X-ray Reports. PMID- 20315250 TI - Tryparsamide Therapy in Neurosyphilis. PMID- 20315251 TI - Prevention and After Care of Acquired Heart Disease in Children. PMID- 20315252 TI - A Case of Tetany treated with Parathyrin. PMID- 20315253 TI - A Case of Diabetes with Tuberculosis x. PMID- 20315254 TI - Multiple Fibromata; A Case with one Fibromata Enlarging into the Stomach. PMID- 20315255 TI - Gangrene of the Lower Extremities Complicating Scarlet Fever. PMID- 20315256 TI - Muscular Dystrophy. PMID- 20315257 TI - Unusual Case of Intestinal Obstruction due to Meckel's Diverticulum and Accompanied by Diffuse Peritonitis. PMID- 20315258 TI - Resume of British Opinion on the Action of Alcohol in Medicine and Its Use as a Beverage. PMID- 20315260 TI - Researches in Scarlet Fever. PMID- 20315259 TI - The Applicability of Urological Methods of Diagnosis to Infants and Children. PMID- 20315262 TI - The Value of Industrial Health Service. PMID- 20315261 TI - Hypertelorism with Remarks upon Anomalies in General. PMID- 20315263 TI - Industrial Medicine. PMID- 20315264 TI - On the Disposition of Ether in the Body. PMID- 20315265 TI - The Immediate Cause of the Acidosis of Anaesthesia. PMID- 20315266 TI - Heart Disease and its Prevention. PMID- 20315267 TI - Inter-State Post-Graduate Assembly. PMID- 20315268 TI - The Use of Opium in India. PMID- 20315269 TI - Relations Between British Medical Association and Canadian Medical Association. PMID- 20315270 TI - Free Clinics. PMID- 20315272 TI - CORRESPONDENCE. PMID- 20315271 TI - Inter-State Post-Graduate Assembly. PMID- 20315273 TI - An Address on the Importance of Second Thoughts in the Management of Some Common Maladies. PMID- 20315274 TI - Mucous Cyst of Caecum (Congenital); Primary Intussusception; General Considerations. PMID- 20315275 TI - A Case of Pigmented Hairy Naevus of the Nose, with Pigmented Hairy and Warty Naevus of the Cheek and Lip; Multiple Autoplasty; Cure. PMID- 20315277 TI - The Newer Methods of Treating Skin Diseases. PMID- 20315276 TI - Surgical Headache. PMID- 20315278 TI - The Nature and Classification of the Leukaemias. PMID- 20315280 TI - Bismuth in Syphilis. PMID- 20315279 TI - The Management of Visceroptosis. PMID- 20315281 TI - The Hormone of Oestrus. PMID- 20315282 TI - Low Systolic Blood Pressure. PMID- 20315283 TI - Some Recent Researches On Iodide and Bromide Eruptions. PMID- 20315284 TI - A Case of Dermatitis Factitia. PMID- 20315285 TI - Carcinoma Caecum. PMID- 20315286 TI - Carcinoma of the Transverse Colon with Partial Destruction of the Bowel Wall and Perforation of a Branch of the Midcolic Artery. PMID- 20315287 TI - An Unusual Uterine Polyp. PMID- 20315288 TI - A Case of Purpura Haemorrhagica; Death due to Cerebral Haemorrhage. PMID- 20315289 TI - Hyperplasia of the Thyroid in an Infant. PMID- 20315290 TI - General Oedema of Foetus. PMID- 20315291 TI - Recent Thoughts on Epilepsy. PMID- 20315292 TI - The Story of Medical Education in London Schools. PMID- 20315293 TI - John Irvine Hunter. PMID- 20315294 TI - First Conference at Ottawa on the Medical Services in Canada. PMID- 20315295 TI - Encephalitis Lethargica. PMID- 20315296 TI - Jaundice. PMID- 20315298 TI - Colloidal Copper Injections in Malignant Disease. PMID- 20315297 TI - On Radium Therapy. PMID- 20315299 TI - On the Biochemistry of Honey. PMID- 20315300 TI - Results Obtained in Baby Welfare Work Among the Poor. PMID- 20315301 TI - Harmonizing Workmen's Compensation Laws. PMID- 20315302 TI - The New Canada Lancet and Practitioner. PMID- 20315303 TI - The Passing of the Anatomy Act. PMID- 20315304 TI - Treatment for Pneumonia. PMID- 20315305 TI - Letters from Medical Missionaries. PMID- 20315307 TI - Letters from Medical Missionaries. PMID- 20315306 TI - Letters from Medical Missionaries. PMID- 20315308 TI - The Duty of the Public to the Profession. PMID- 20315309 TI - Health Surveys, Health Nurses, and the Relation of the Medical Profession Thereto. PMID- 20315310 TI - Medical Licensure. PMID- 20315311 TI - License Inspectors. PMID- 20315312 TI - Public Health Work in Saskatchewan. PMID- 20315313 TI - The Notification of Communicable Disease. PMID- 20315314 TI - The Greatest Public Health Need of Canada. PMID- 20315315 TI - Health Insurance. PMID- 20315316 TI - On Maternal Mortality in Canada. PMID- 20315318 TI - The Purity and Potency of Drugs. PMID- 20315317 TI - Classification of Medical Schools. PMID- 20315319 TI - Medical Education. PMID- 20315320 TI - Medical Education. PMID- 20315321 TI - Post-Graduate Medical Education in Canada. PMID- 20315322 TI - A Western Impression of the Conference. PMID- 20315323 TI - The First National Conference of the Medical Services in Canada. PMID- 20315324 TI - Pioneers of Medicine in Canada. PMID- 20315325 TI - An Address on Arterial Disease and Renal Incompetence. PMID- 20315326 TI - Anatomical Changes in Relation to the Functional Disturbances in "Chronic Nephritis" more Especially in the contracted Kidney Types. PMID- 20315327 TI - Congenital Dilatation of the Ureters. PMID- 20315328 TI - A Case of Amaurotic Family Idiocy in an Infant of Non-Semitic Parentage. PMID- 20315329 TI - A Case of Cirrhosis of the Liver in a Child Fourteen Months of Age. PMID- 20315331 TI - Radiation in the Treatment of Benign Diseases of the Female Pelvis. PMID- 20315330 TI - Observations on the Use of Dihydroxyacetone in the Treatment of Diabetes Mellitus: (Preliminary Report). PMID- 20315332 TI - The Treatment of the Pernicious Vomiting of Pregnancy. PMID- 20315333 TI - The Physician in His Relationship to Industrial Toxication. PMID- 20315334 TI - The Preservation of Blood Samples for Chemical Analysis. PMID- 20315335 TI - Diabetes Insipidus. PMID- 20315336 TI - Medical Examination of School Children. PMID- 20315337 TI - Results of Operations on the Thyroglossal Tract and a Note on Thyroid Secretions. PMID- 20315338 TI - A Case Showing Unusual Distribution of Icteroid Pigmentation. PMID- 20315339 TI - Three Cases of Creeping Myiasis in Saskatchewan. PMID- 20315340 TI - A Case of Epidermolysis Bullosa. PMID- 20315341 TI - Case of Streptococcus Septicaemia Cured by Mercurochrome. PMID- 20315342 TI - Multiple Ulcers of the Duodenum and Stomach, with Diverticulum of the Duodenum, Perforation of the Duodenum and Pulmonary Infarct. PMID- 20315344 TI - Studies in Addison's Disease: The Muirhead Treatment. PMID- 20315343 TI - A New Treatment for Tuberculosis Under Trial. PMID- 20315345 TI - Dioxyacetone. PMID- 20315347 TI - A Recent Epidemic of Typhoid Fever and Its Cause. PMID- 20315346 TI - Mathematics and the Physician. PMID- 20315348 TI - A Memorial to Sir James Mackenzie. PMID- 20315349 TI - Guy's Hospital Gazette Bicentenary Number. PMID- 20315350 TI - The Trudeau Sanatorium, 1885-1925. PMID- 20315351 TI - Importance of Rest and Posture in Fatigue. PMID- 20315352 TI - EDITORIAL COMMENT. PMID- 20315353 TI - Physiological Abstracts. PMID- 20315354 TI - The First Medical School in Canada : Its History and Founders, with Some Personal Reminiscences. PMID- 20315355 TI - On the Release of Codein and Dionin from the List of Scheduled Narcotics. PMID- 20315356 TI - The Medical Witness : Historical Sketch of the Medical Witness. PMID- 20315357 TI - An Address on Cancer Prophylaxis. PMID- 20315358 TI - Periarteritis Nodosa: A Review of our Knowledge. PMID- 20315359 TI - The Problem of the Fundamental Action of Insulin. PMID- 20315361 TI - A Brief Review of Forty-five Cases of Anterior Poliomyelitis. PMID- 20315360 TI - Colles' Fracture. PMID- 20315362 TI - X-ray Findings in Primary Carcinoma of the Lung. PMID- 20315363 TI - Newer Methods for the Determination of Pregnancy. PMID- 20315364 TI - Pyelitis of Pregnancy. PMID- 20315365 TI - Extreme Sensitization in Infants to Cows' Milk Protein : Diagnosis and Treatment. PMID- 20315366 TI - Multiple Myelomata with Report of a Case. PMID- 20315367 TI - Some Remarks on Industrial Diseases in Ontario. PMID- 20315368 TI - Industrial Toxications under the Workmen's Compensation Act. PMID- 20315369 TI - Report of the Use of Lipiodol in the Diagnosis of Cord Tumour. PMID- 20315370 TI - Fatal Haemorrhage from a Duodenal Ulcer, associated with a Toxic Adenoma of the Thyroid Gland. PMID- 20315371 TI - A Case of Internal Hernia of Purely Pathological Origin. PMID- 20315372 TI - A Case of Diabetic Coma Treated with Dioxyacetone, with Recovery. PMID- 20315373 TI - A Case of Sprue. PMID- 20315374 TI - Hospital Notes. PMID- 20315375 TI - Tuberculosis in Children. PMID- 20315377 TI - Infantile Paralysis and Cerebro-spinal Infections. PMID- 20315376 TI - The Artificial Feeding of Normal Infants with Sweet Cows' Milk. PMID- 20315378 TI - The Function of the Scrotum. PMID- 20315380 TI - Ultra Violet Rays. PMID- 20315379 TI - Parathyroid Extract in the Treatment of Sprue. PMID- 20315382 TI - Nineteen Twenty-four Our Best Health Year. PMID- 20315381 TI - Lime Dermatitis. PMID- 20315383 TI - On Oxaluria. PMID- 20315384 TI - The James Mackenzie Institute for Clinical Research, St. Andrew's. PMID- 20315385 TI - The Saskatchewan Epidemic of Poliomyeloencephalitis. PMID- 20315387 TI - On the Passing of the Anatomy Act: I. PMID- 20315386 TI - Historical Sketch of the Dalhousie Medical School. PMID- 20315389 TI - On the Passing of the Anatomy Act: IV. PMID- 20315388 TI - On the Passing of the Anatomy Act: II. PMID- 20315390 TI - On the Passing of the Anatomy Act: III. PMID- 20315391 TI - The Farris Libel Suit. PMID- 20315392 TI - CORRESPONDENCE. PMID- 20315393 TI - Letter from China. PMID- 20315394 TI - Medico-Legal. PMID- 20315396 TI - An Address on the Scientific Method in Medicine. PMID- 20315395 TI - ASSOCIATION NOTES. PMID- 20315397 TI - The Management of Gastric and Duodenal Ulcers. PMID- 20315398 TI - The Present Status of Hepatic Efficiency Tests. PMID- 20315399 TI - Two Cases of Adolescent Myxoedema Accompanied by Nephrosis, and in one Case, Tetany. PMID- 20315400 TI - The Diabetic as a Surgical Risk. PMID- 20315401 TI - Goitre from the Medical Standpoint. PMID- 20315402 TI - The Surgical Management of Goitre. PMID- 20315403 TI - A Consideration of the Aetiology of Rheumatic Endocarditis. PMID- 20315404 TI - The Physician and the Benefit Association in Industry. PMID- 20315405 TI - A Health Week in Lambton County by the Department of Public Health, Ontario. PMID- 20315406 TI - A Plea for the use of the "Combined Treatment" in Affections Other than those of the Eye. PMID- 20315407 TI - The X-ray Treatment of Tonsils and Adenoids. PMID- 20315408 TI - Primary Sarcoma of Bladder. PMID- 20315409 TI - Intractable Sciatica. The Sacral Epidural Injection; An Effective Method of Giving Relief. PMID- 20315410 TI - An Unusual Case of Anthrax in Man. PMID- 20315411 TI - Case of Recent and Old Haemorrhages of the Brain. PMID- 20315412 TI - Twilight Sleep in Obstetrical Practice with Reports of Cases. PMID- 20315413 TI - An Unusual Case of Acute Lead Pcisoning. PMID- 20315414 TI - A Case of Duodenal Ulcer. PMID- 20315415 TI - ASSOCIATION NOTES. PMID- 20315416 TI - The Life Cycle of Peptic Ulcers. PMID- 20315417 TI - On the industrial Worker. PMID- 20315418 TI - The Psychology of the Miner. PMID- 20315419 TI - The Influence of Cereal Foods as a Factor in Rickets. PMID- 20315420 TI - Influences Affecting Lactation. PMID- 20315421 TI - Increase of the Anti-Rachitic Power by Irradiation of Milk and Other Foods. PMID- 20315422 TI - Locke on the Upbringing of Children. PMID- 20315423 TI - Iconography of Andreas Vesalius. PMID- 20315424 TI - Smallpox and Vaccination. PMID- 20315425 TI - Cocaine Addiction. PMID- 20315426 TI - Jewish University on Mount Scopus. PMID- 20315427 TI - On Drug Addiction in the States. PMID- 20315428 TI - Contributions to the Lister Memorial Club of the Canadian Medical Association to May 1st, 1925. PMID- 20315429 TI - The Prevention and Treatment of Post-operative Pulmonary Affections. PMID- 20315430 TI - HOW TO DRY AND CLEAN HYPODERMIC NEEDLES. PMID- 20315431 TI - An Address on the Trend of Medical Education and Medical Service. PMID- 20315432 TI - An Address on the Present Standing of Therapeutics. PMID- 20315433 TI - An Address on the Successive Stages in the Control of Tuberculosis. PMID- 20315434 TI - Extractives of Liver Possessing Blood Pressure Reducing Properties. PMID- 20315435 TI - The Control of Blood Pressure with Liver Extracts. PMID- 20315436 TI - Bacterial Phagocytosis by the Epitherial Cells of the Conjunctiva. PMID- 20315437 TI - The Morbid Anatomy of Rheumatic Fever. PMID- 20315438 TI - Acute Septic Tracheitis. PMID- 20315439 TI - Rheumatic Fever in Childhood. PMID- 20315440 TI - Failing Vision after Middle Life Without Associated Pain. PMID- 20315441 TI - Infections of the Hand. PMID- 20315442 TI - The Influence of Natural Chemical Stimuli on the Movements of the Alimentary Canal. PMID- 20315443 TI - Observations on the Value of the Diazo-Colour-Reaction in the Differential Diagnosis of Uraemia. PMID- 20315444 TI - Some Disadvantages of the Workmen's Compensation Act which Lead the Employer to be less interested in the Health of the Employee. PMID- 20315445 TI - The Post-Operative Treatment of Flexion at the Hip. PMID- 20315446 TI - Lobar Pneumonia Complicated by Diphtheria and Parotitis in a Child of Four Years. PMID- 20315448 TI - On the Influence of the Liver on Arterial Hypertension. PMID- 20315447 TI - Retro-Pharyngeal Abscess. PMID- 20315450 TI - Ansaethesia and the Newer Anaesthetics. PMID- 20315449 TI - Theories and Hypotheses in Immunology. PMID- 20315451 TI - Industrial Fatigue. PMID- 20315452 TI - Thermogenesis as the Fundamental Function of the Adrenal Medulla and Cortex. PMID- 20315453 TI - The Gold Treatment of Tuberculosis Again. PMID- 20315454 TI - Strychnine Poisoning Met with in Children. PMID- 20315455 TI - On the Value of Holidays. PMID- 20315456 TI - Generous donation by The Sun Life Assurance Company for Post-Graduate work in Canada. PMID- 20315457 TI - Huxley's Centenary. PMID- 20315459 TI - Gordon Bell Memorial Lecture. PMID- 20315458 TI - Race Control. PMID- 20315461 TI - Industrial Hygiene in Moscow. PMID- 20315460 TI - World Prevalence of Human Plague during 1923. PMID- 20315462 TI - Malaria Control in Palestine. PMID- 20315463 TI - An Aspirator. PMID- 20315464 TI - Infraction of the Liquor Law in Alberta. PMID- 20315465 TI - Fourth International Medical Congress of Industrial Accidents and Diseases, Amsterdam, September, 1925. PMID- 20315466 TI - An Address on Uraemia and Nephritis. PMID- 20315467 TI - The Determination of Kidney Function in Private Practice. PMID- 20315468 TI - Quinidine Sulphate in Cardiac Irregularities. PMID- 20315469 TI - Erythema Nodosum. PMID- 20315470 TI - A Sensitive Test for Hexyl-resorcinol in Body Fluids and Notes on Its Application. PMID- 20315471 TI - Abortions and Their Treatment. PMID- 20315472 TI - Mordern Advances in Diagnosis (of Tuberculosis). PMID- 20315473 TI - Tuberculosis in the Child; Preventive Role of the Open Air School; The Summer Camp; The Preventorium. PMID- 20315474 TI - The Most Important Agencies in a Provincial Campaign Against Tuberculosis. PMID- 20315475 TI - A Case of Adolescent Myxoedema, accompanied by Nephrosis and by Tetany of Parathyroid Origin, treated with Thyroid and Collip's Parathyroid Extract. PMID- 20315476 TI - Atelectasis of the Lung. PMID- 20315477 TI - The Tuberculosis Survey of School Children in Alberta, 1924. PMID- 20315478 TI - The Travelling Diagnostic Clinic for Diseases of the Lungs. PMID- 20315479 TI - Treating Tuberculosis in the Dry Climate Belt. PMID- 20315480 TI - The Evaluation of Tuberculosis Losses. PMID- 20315481 TI - The Role of the Ultra-violet Ray in the Treatment of Tuberculosis. PMID- 20315482 TI - Results of Artificial Pneumothorax Treatment of the Muskoka Institutions of the National Sanitarium Association. PMID- 20315483 TI - Standards in Chest Radiography. PMID- 20315484 TI - A Case of Silicosis with Autopsy. PMID- 20315485 TI - Thymic Death in Child with Glandular Family History. PMID- 20315486 TI - Tuberculosis of Inguinal Glands. PMID- 20315487 TI - Anti-Tuberculosis Work in Canada. PMID- 20315488 TI - Sleep and Sleeplessness. PMID- 20315489 TI - Hypodermic Vaccination. PMID- 20315490 TI - The Use of Physostigmin in Abdominal Distension. PMID- 20315491 TI - Nephrosis. PMID- 20315492 TI - Dangers from Undue Exposure to Ultra-violet Rays. PMID- 20315494 TI - Blood Volume and Composition in Oedema. PMID- 20315493 TI - "Itis". PMID- 20315495 TI - Other Things-and Pomander Sticks. PMID- 20315496 TI - The Life of Sir William Osler. PMID- 20315497 TI - Ontario Medical Association Meeting. PMID- 20315499 TI - A Medical Report. PMID- 20315498 TI - A New Blood Transfusion Apparatus. PMID- 20315500 TI - An Address on Surgical Treatment of Gastric and Duodenal Ulcer. PMID- 20315501 TI - Rheumatoid Arthritis; Its Causation and Treatment. PMID- 20315502 TI - Tumours of the Large Bowel. PMID- 20315503 TI - Primary Papillary Epithelioma of the Ureter : Report of a Case. PMID- 20315504 TI - Deficiency Diseases of Children. PMID- 20315505 TI - A New Technique in the Application of Thiersch Skin Grafts. PMID- 20315506 TI - The Arrest of Leutic Optic Atrophy by Cisternal Injection of Mercury. PMID- 20315507 TI - Calcium and Potassium Chlorides in the Treatment of Arterial Hypertension. PMID- 20315508 TI - Peripheral Nerve Injuries. PMID- 20315510 TI - The Infectious Arthritides. PMID- 20315509 TI - Bladder Neoplasms with a Brief Series. PMID- 20315511 TI - Rectal Anaesthesia in Obstetrics. PMID- 20315512 TI - Cancer of the Larynx. PMID- 20315513 TI - Maternal Mortality. PMID- 20315514 TI - Intracranial Dermoid Cyst. PMID- 20315515 TI - Spontaneous Pneumoperitoneum. PMID- 20315516 TI - Case of Infected Thrombus. PMID- 20315517 TI - A Canadian's Impression of the Recent Meeting of the British Medical Association in the City of Bath. PMID- 20315518 TI - Puerperal Sepsis. PMID- 20315519 TI - Some Problems of Thyroid Disease. PMID- 20315520 TI - Viability of the Bacillus Typhus in Oysters. PMID- 20315521 TI - On Glacier Lassitude. PMID- 20315522 TI - The "Cause" of Cancer. PMID- 20315523 TI - Cancer in Canada. PMID- 20315525 TI - Notes on Organization of Banting Research Foundation. PMID- 20315524 TI - The Last Hundred Days of the Great War. PMID- 20315527 TI - Inter-State Post-Graduate Assembly of America. PMID- 20315526 TI - Analysis of a Patent Medicine. PMID- 20315528 TI - X-ray Demonstration of Pulmonary Changes in Tuberculosis by Lipiodol Injection. PMID- 20315530 TI - Familial Icterus Gravis of the New-Born and its Treatment. PMID- 20315529 TI - On Some Aspects of the Cultural Study of the Ringworm Fungi. PMID- 20315531 TI - Amoebic Dysentery in Canada. PMID- 20315533 TI - Basal Metabolic Determinations in 250 Winnipeg School Children. PMID- 20315532 TI - Some Studies on the Incidence of Goitre Among School Children in Manitoba. PMID- 20315534 TI - The Goitre Problem. PMID- 20315535 TI - The Use and Abuse of the Obstetrical Forceps. PMID- 20315536 TI - Urinary Retention. PMID- 20315537 TI - Bladder Neck Obstructions. How Can the Operative Mortality be Lowered and the End Results Improved. PMID- 20315538 TI - Gastric and Duodenal Ulcer; Diagnosis, Treatment, and Indications for Surgery. PMID- 20315539 TI - Cancer of the Lower Lip. PMID- 20315540 TI - Necessity of Effective Organization in Public Health Departments. PMID- 20315541 TI - Familial Tendency in Angina Pectoris. PMID- 20315542 TI - Case of Larvae of Fly in Tympanum. PMID- 20315544 TI - Health Units in Outlying Districts. PMID- 20315543 TI - Backache and Sciatica of Bone and Joint Origin. PMID- 20315545 TI - The Writing of Medical Histories. PMID- 20315546 TI - The Progress of Radiology. PMID- 20315547 TI - Alcohol in Therapeutics. PMID- 20315548 TI - On Birth Control. PMID- 20315549 TI - The Influence of Prolonged Swimming in Favouring Infections of The Upper Respiratory Passages. PMID- 20315550 TI - Canadian Medical Protective Association. PMID- 20315551 TI - The Post-Graduate Courses of the Fellowship of Medicine. PMID- 20315553 TI - Criticism on Gye and Barnard's Cancer Findings. PMID- 20315552 TI - A "Canadian Number" from Australia. PMID- 20315555 TI - Cancer of the Colon : Its Diagnosis and Treatment. PMID- 20315554 TI - Presidential Address in Section of Medicine. PMID- 20315556 TI - The Injection of Lipiodol as an Aid in the X-ray Diagnosis of Broncho-pulmonary Lesions including Tuberculosis: Preliminary Report. PMID- 20315557 TI - High Blood Pressure. PMID- 20315558 TI - The Relation Between Gastric Acidity and the Hydrogen Concentration of the Urine with a Study of the Effect of Histamine. PMID- 20315559 TI - Simplicity in the Management of the Diabetic. PMID- 20315560 TI - Basal Blood Pressure. PMID- 20315561 TI - Pyelitis Manifesting Acute Abdominal Symptoms. PMID- 20315562 TI - The Surgical Treatment of Trigeminal Neuralgia. PMID- 20315564 TI - Backache. PMID- 20315563 TI - Ulcerative Colitis: Report of a Case Requiring a Permanent Colostomy. PMID- 20315565 TI - The Relief of Chronic Pain in the Lower Segments of the Body by the Sacral Epidural Injection. PMID- 20315567 TI - Epiphora and Catarrhal Affections of the Nose, with Their Treatment. PMID- 20315566 TI - The Colloidal Gold Reaction of the Cerebrospinal Fluid. PMID- 20315568 TI - Etiology of Cough. PMID- 20315569 TI - Foreign Object in Bronchus Simulating Pulmonary Tuberculosis. PMID- 20315570 TI - Multiple Laryngeal Papillomata (Sub-Glottic) in a Child. PMID- 20315571 TI - Rupture of the Bladder. PMID- 20315572 TI - Foreign Body in Bronchus. PMID- 20315573 TI - Prostatic Hypertrophy. PMID- 20315574 TI - The Work of the Health Organization of the League of Nations. PMID- 20315575 TI - The Problem of the Possible Induction of Immunity in Cancer. PMID- 20315576 TI - The Value of Iron in Anaemia. PMID- 20315577 TI - The Necessity of Standardization in Commercial Thyroid Preparations. PMID- 20315578 TI - Desirability of an Early Diagnosis in the Treatment of Cretinism. PMID- 20315579 TI - Ephedrine-A New (?) Sympathomimetic Drug. PMID- 20315580 TI - Clinical Use of the Parathyroid Hormone. PMID- 20315581 TI - The Control of Rickets. PMID- 20315582 TI - Dihydroxyacetone. PMID- 20315583 TI - On Cascara. PMID- 20315584 TI - ERRATA. PMID- 20315585 TI - Resignation of Sir Henry Gray. PMID- 20315587 TI - "Fashions and Fads in Medicine". PMID- 20315586 TI - CORRESPONDENCE. PMID- 20315588 TI - Military Hospitals, D.S.C.R. PMID- 20315589 TI - Contacts with Nature in Medical Practice. PMID- 20315590 TI - On the Appreciation of Anatomical Relationships. PMID- 20315591 TI - The Value of X-rays in Obstetrics. PMID- 20315592 TI - The Classification of Post-Operative Pulmonary Lesions. PMID- 20315593 TI - The Evaluation of Surgical Risks from the Standpoint of the General Practitioner. PMID- 20315594 TI - Physiotherapy. PMID- 20315595 TI - Osteomyelitis: Its Treatment with Special Reference to the Use of Bipp. PMID- 20315596 TI - Fractures. PMID- 20315597 TI - Acute Suppurative Appendicitis. PMID- 20315598 TI - Recent Advances in Surgery. PMID- 20315599 TI - An Obstetrical Retrospect. PMID- 20315600 TI - Bronchial Asthma: An Investigation of Twenty-Eight Cases. PMID- 20315601 TI - Mal de Siam. PMID- 20315602 TI - The Importance of the Dental Surgeon in Medicine and the Value of Radiography in Dental Practice. PMID- 20315603 TI - Fracture of the Skull in a Child, Treated by Repeated Puncture of the Cisterna Magna. PMID- 20315604 TI - Case of Larva Migrans. PMID- 20315605 TI - Carcinoma of the Thyroid with Metastases. PMID- 20315606 TI - Experiments with a New Vaccine Against Tuberculosis. PMID- 20315607 TI - The New United States Pharmacopoeia. PMID- 20315608 TI - Local Anaesthetics-A Step Forward. PMID- 20315609 TI - The Importance of Ventilation in Factories. PMID- 20315610 TI - Importance of Sufficient Relative Humidity in Air of Dwellings. PMID- 20315611 TI - The Unexpected in Disease. PMID- 20315612 TI - Smallpox. PMID- 20315613 TI - On the Prevalence of Typhoid Carriers. PMID- 20315614 TI - Value of the Digestive Enzymes in Therapeutics. PMID- 20315615 TI - Visual Disturbances Induced by Digitalis. PMID- 20315616 TI - When the Reed Breaks. PMID- 20315617 TI - Recreation for the Physician-Professor R. Tait Mackenzie. PMID- 20315618 TI - Small Perforations of the Nasal Septum and My Method of Treatment. PMID- 20315619 TI - To the Members of the British Medical Association in Canada. PMID- 20315620 TI - The Human Touch in Professional Life. PMID- 20315621 TI - Lister Memorial Fund. Supplementary List of Contributions from May 1 to October 1, 1925. PMID- 20315622 TI - FOREWORD 1926. PMID- 20315623 TI - An Address on Arteriosclerosis. PMID- 20315624 TI - An Address on Man's Structural Imperfections: Abstract of the Lloyd Roberts Lecture to the Royal Society of Medicine. PMID- 20315625 TI - An Address on Preventive Medicine. PMID- 20315626 TI - Osteopathy and Chiropractic. PMID- 20315627 TI - Some Effects of Anoxaemia on the Circulation. PMID- 20315628 TI - Cancer and Race. PMID- 20315629 TI - On the Use of the Low Cervical Operations for Caesarean Section. PMID- 20315630 TI - Acute Rheumatic Fever and Chorea in Children: An Analysis of 100 Cases Treated in the Wards of the Children's Memorial Hospital, Montreal. PMID- 20315631 TI - Caecal Stasis. PMID- 20315632 TI - Anatomical Note on a Possible Source of Error in X-ray findings of the Normal Vertebral Column. PMID- 20315633 TI - Spinal Metastasis from Breast Carcinoma. PMID- 20315635 TI - Trench Mouth. PMID- 20315634 TI - Photography as applied to Dermatology. PMID- 20315636 TI - A Resume of the Therapeutic Value of X-rays. PMID- 20315637 TI - Case of Pseudo-Bulbar Paralysis. PMID- 20315638 TI - Lung Abscess following the Removal of Teeth under General Anaesthetic. PMID- 20315639 TI - Food Anaphylaxis. PMID- 20315640 TI - Centenary of First Canadian Medical Journal. PMID- 20315642 TI - Colloidal Lead and the Control of Cancer. PMID- 20315641 TI - Weighing Versus Counting. PMID- 20315643 TI - The Functions of the Liver and the Tests for Their Activity. PMID- 20315644 TI - On the Importance of Body Weight. PMID- 20315645 TI - Defective Vision in School Children. PMID- 20315646 TI - On Physical Education. PMID- 20315647 TI - The Preliminary Education of the Medical Student. PMID- 20315648 TI - An Address on the Treatment of Pneumonia. PMID- 20315650 TI - Direct Smear in the Diagnosis of Acute Throat Infections. PMID- 20315649 TI - Treatment of Pertussis. PMID- 20315651 TI - On the Prevention of Carious Teeth in Children. PMID- 20315652 TI - Serum in the Treatment of Acute Poliomyelitis. PMID- 20315653 TI - Mortality Records for 1925. PMID- 20315654 TI - An Osler Memorial Volume. PMID- 20315655 TI - Annual Report of the Canadian Tuberculosis. PMID- 20315656 TI - Seven Years Afterwards. PMID- 20315657 TI - Obscure Pyrexia in Childhood. PMID- 20315658 TI - Judgment rendered in the Case of Dr. C. W. Hunt: Appealing Against the Judgment of the College of Physicians and Surgeons of the Province of Saskatchewan by His Honour Judge Mackenzie in the King's Bench Court. PMID- 20315659 TI - An Address on Epigastric Distress: Functional Causes and Treatment. PMID- 20315660 TI - An Address on Carcinoma of the Large Bowel. PMID- 20315661 TI - An Address on Some Cases of Pyrexia without Physical Signs. PMID- 20315662 TI - The Atomic Processes of Disease. PMID- 20315663 TI - Scleroderma and Its Treatment by Radium: A Preliminary Report. PMID- 20315664 TI - Primary Repair of Injuries to the Parotid Duct. PMID- 20315665 TI - The Significance of Haematuria. PMID- 20315666 TI - Gassy Indigestion: Its Significance as a Symptom of Gall Bladder Disease, With a Review of Sixty Cases of Cholecystectomy. PMID- 20315667 TI - Essential Thrombocytopenic Purpura Haemorrhagica. PMID- 20315668 TI - Pyaemia After Scarlet Fever. PMID- 20315669 TI - A Comparative Study of the Effect of Two Different Preparations of Iodine upon the Preoperative Basal Metabolic Rate in Exophthalmic Goitre. PMID- 20315670 TI - A Clinical Study of the Colloidal Benzoin Reaction. PMID- 20315671 TI - Profuse Haemoptysis Arising from A Small Area of Bronchiectasis Followed by Brain Abscess. PMID- 20315672 TI - Case of Acute Lymphatic Leukaemia: Death in Five Weeks. PMID- 20315673 TI - Abscess of the Lung: Report of a Case in an Infant Twenty-four Days of Age. PMID- 20315674 TI - Fracture of Semilunar Bone Due to Indirect Violence. PMID- 20315675 TI - Abortion of One Twin: Delivery of Second at Term. PMID- 20315676 TI - The Mechanism of Pigment Formation in the Skin : A Review. PMID- 20315678 TI - A Discussion on Hyperpiesis. PMID- 20315677 TI - Recent Advances in Haematology: 1. The Origin of the Red Blood Cell in Adult Marrow. PMID- 20315679 TI - Intracardiac Surgery. PMID- 20315681 TI - Novasurol. PMID- 20315680 TI - On Right and Left Handedness in Modern and in Primitive Man. PMID- 20315683 TI - Haemorrhage in Pulmonary Tuberculosis. PMID- 20315682 TI - Rehabilitation of the Tuberculous. PMID- 20315684 TI - Comparison of the Two Hyoscines. PMID- 20315685 TI - Evil of Smoke Pollution in Large Cities. PMID- 20315686 TI - Hospital Dietaries. PMID- 20315687 TI - The William Gibson Research Scholarship for Medical Women. PMID- 20315688 TI - ASSOCIATION NOTES. PMID- 20315689 TI - Jacques Bourgeois. Chirurgien 1621-1701. PMID- 20315690 TI - The Centenary of Charcot. PMID- 20315692 TI - Vienna as a Post-Graduate Centre. PMID- 20315691 TI - Puerperal Sepsis. PMID- 20315693 TI - Medicine as a Career for Women. PMID- 20315695 TI - An Address on Diabetes and Insulin: Being The Nobel Lecture Delivered at Stockholm on September 15th, 1925. PMID- 20315694 TI - A Survey of Post-Graduate Teaching in Oto-Laryngology in Certain European Centres. PMID- 20315696 TI - An Address on the Hospital: Its Long Crusade. PMID- 20315697 TI - An Address on Involutionary Changes in Prostate and Female Breast in Relation to Cancer Development. PMID- 20315698 TI - Hypertonic Saline in Adynamic Ileus. PMID- 20315699 TI - Studies in Pernicious Anaemia. I. The Outstanding Clinical Problem and the Geographical Distribution in Western Canada. PMID- 20315701 TI - The Diagnosis and Treatment of Obstruction of the Small Intestine in Adults. PMID- 20315700 TI - Studies in Pernicious Anaemia. II. Chloride Metabolism in the Anaemias, Especially Pernicious Anaemia. PMID- 20315702 TI - Arteriotomy for Embolus Obstructing the Circulation in an Extremity, Illustrated by Successful Case. PMID- 20315703 TI - The Industrial Physician. PMID- 20315704 TI - The Physician in Industry: Report of a Sub-Committee of the Committee on industrial Medicine, Ontario Medical Association. PMID- 20315705 TI - Briefly Drawn Diagnostic Pictures of Industrial Intoxication by Lead, Benzol and Nickel. PMID- 20315706 TI - Notification of Occupational Diseases. PMID- 20315707 TI - The Handicapped Surgical Patient. I. The Diabetic Patient. PMID- 20315708 TI - The Handicapped Surgical Patient. II. Due to Cardiovascular Disease. PMID- 20315709 TI - The Handicapped Surgical Patient. III. Due to Benign Hypertrophy of the Prostate. PMID- 20315710 TI - Rabies. PMID- 20315711 TI - The Toxaemias of Pregnancy from the View-point of Etiology. PMID- 20315712 TI - Oedema of both Optic Discs; Tumour in the Substance of the Cerebellum. PMID- 20315713 TI - An Obscure Case of Acute Intestinal Obstruction due to presence in Mesentery of Small Intestine of a Fibrous Polyp undergoing Calcarious Degeneration. PMID- 20315714 TI - A Case of Apparent Homolateral Hemiplegia. PMID- 20315715 TI - Spontaneous Rupture of Eyeball. PMID- 20315716 TI - The Nobel Lecture on Diabetes and Insulin. PMID- 20315717 TI - Periodic Health Examinations. PMID- 20315718 TI - Industrial Disease and the Profession. PMID- 20315719 TI - Light, Photosynthesia and Vitamines. PMID- 20315720 TI - Carbon Dioxide and Respiration. PMID- 20315721 TI - The Action of Insulin on Carbohydrate Metabolism. PMID- 20315722 TI - An Osler Memorial. PMID- 20315723 TI - Cancer. PMID- 20315724 TI - A Plea for the Use of "The Combined Treatment" in Affections other than those of the Eye. PMID- 20315725 TI - The Story of Fifty-Four Years' Quarantine Service from 1866 to 1920. PMID- 20315726 TI - The Death of the Duke of Richmond from Hydrophobia in 1820. PMID- 20315727 TI - An Address on Nephrosis. PMID- 20315729 TI - X-rays and Radium in the Management of Breast Carcinoma. PMID- 20315728 TI - Complement in Health and in Disease. PMID- 20315730 TI - The Influence of Dihydroxyacetone upon the Blood Sugar and Glycosuria. PMID- 20315731 TI - The Definition and Classification of the Pseudo-Leukaemias. PMID- 20315732 TI - Haemolytic Jaundice Associated with Splenomegaly. PMID- 20315733 TI - Splenectomy for Purpura Haemorrhagica. PMID- 20315734 TI - Blood Regeneration. PMID- 20315735 TI - Leprosy in Canada: Report of a Case. PMID- 20315736 TI - Plaster Shells in the Treatment of Tuberculosis and Fracture of the Spine. PMID- 20315737 TI - A Case of Corrosive Sublimate Poisoning by the Genital Tract. PMID- 20315738 TI - A Case of Endothelioma with Xanthochromia. PMID- 20315739 TI - The Potency of Tinctures of Digitalis and Strophanthus Purchased at Various Points on the Canadian Market. PMID- 20315740 TI - The Use of Non-Specific Foreign Protein in the Treatment of Inflammatory Lesions in the Female Pelvic Organs. PMID- 20315741 TI - Tuberculous Complications in the Digestive Tract Met with in the Course of Pulmonary Disease. PMID- 20315742 TI - The Use of Ephedrin in Bronchial Asthma. PMID- 20315743 TI - Tracheal Collapse During Thyroidectomy. PMID- 20315744 TI - A Case of Obstinate Urethral and Rectal Retention Cured by Psycho-Analytic Methods. PMID- 20315745 TI - Phrenicotomy in Traumatic Injury to the Chest. PMID- 20315746 TI - Non-Toxic Goitre with Nervous Symptoms. PMID- 20315747 TI - Pituitary Extract in Asphyxia Pallida. PMID- 20315748 TI - Recent Advances in Haematology: II. Laboratory Aids in the Diagnosis of Anaemia. PMID- 20315750 TI - Complement in Health and Disease. PMID- 20315749 TI - On Extra-Pleural Thoracoplasty. PMID- 20315752 TI - Vitamines. PMID- 20315751 TI - On The Standardization of Important Drugs. PMID- 20315753 TI - Focal Sepsis. PMID- 20315754 TI - Human and Bovine Tuberculosis. PMID- 20315755 TI - The Seasonal Occurrence of Infectious Nervous Diseases. PMID- 20315756 TI - Nature of Tumour Formation. PMID- 20315757 TI - Cancer Inquiry of the League of Nations: Incidence of Cancer in Different Countries. PMID- 20315758 TI - Medical Reciprocity with Italy. PMID- 20315759 TI - Valuable Cinchona Alkaloids. PMID- 20315760 TI - Shantung University. PMID- 20315761 TI - A Cheap Sterilizable Dialyzing Medium. PMID- 20315762 TI - Colloids in the Treatment of Cancer. PMID- 20315763 TI - The Use of Chloroform. PMID- 20315764 TI - The Royal Society of Medicine. PMID- 20315766 TI - Plague in Canada. PMID- 20315765 TI - An Historical Sketch of the Medical Profession of Toronto. PMID- 20315767 TI - Practising Under Difficulties. PMID- 20315768 TI - Sunlight Treatment: Artificial and Natural. PMID- 20315769 TI - An Address on Modern Methods in the Diagnosis and Treatment of Heart Disease. PMID- 20315770 TI - An Address on Cardiac and Renal Disease. PMID- 20315771 TI - An Address on Classfication of the Diarrhoeas, with an outline of Treatment. PMID- 20315772 TI - An Address on the Medical Aspects of Diseases of the Large Bowel. PMID- 20315773 TI - Differential Diagnosis of Upper Gastro-Intestinal Lesions. PMID- 20315774 TI - The Management of Gastric and Duodenal Ulcer. PMID- 20315775 TI - The Etiology of Malignant Neoplasms. PMID- 20315776 TI - Pernicious Anaemia-like Blood Changes in Rabbits accompanying B. Welchii Infections. PMID- 20315777 TI - Tuberculosis of the Tongue. PMID- 20315778 TI - Lung Expansion after Acute Empyema. PMID- 20315779 TI - A Case of Chronic Nephritis Treated with Collip's Parathyroid Extract. PMID- 20315780 TI - A Case of Status Epilepticus (Traumatica) Operation; Recovery. PMID- 20315781 TI - The Treatment of Diabetes Mellitus, with and without Insulin. PMID- 20315782 TI - Pyelitis in Infancy a Pathological Study. PMID- 20315783 TI - The Control of Arsphenamine Treatment by Liver Function Tests. PMID- 20315785 TI - The Treatment of Incomplete Abortion. PMID- 20315784 TI - Purpura with Intense Abdominal Pain as a Late Complication of Scarlet Fever. PMID- 20315786 TI - Sudden Death in Case of Status Lymphaticus: History with Pathological Report. PMID- 20315787 TI - Rhino-Plasty with Ivory Transplant. PMID- 20315788 TI - Late Decompression of Lumbar Cord Following Injury. PMID- 20315789 TI - Syphilitic Periostitis of the Cervical Vertebrae and Right Clavicle. PMID- 20315790 TI - On Splenectomy. PMID- 20315791 TI - Immunization Against Tuberculous Infection. PMID- 20315793 TI - Myopia and its Treatment. PMID- 20315792 TI - On Ventilation. PMID- 20315795 TI - Report of the Coal Commission in England. PMID- 20315794 TI - The Investigation of the Structure of the Eye and of Pathological Change in it by Means of Various Light Rays. PMID- 20315796 TI - The Opium Evil in India. PMID- 20315797 TI - Treatment with Artificial Light in Glasgow Clinics. PMID- 20315798 TI - On Morphine and Heroin Addiction. PMID- 20315799 TI - Experiences in Deep Diving. PMID- 20315800 TI - Osler Memorial Volume. PMID- 20315801 TI - Accident Prevention Among School Children. PMID- 20315802 TI - American Health Congress. PMID- 20315803 TI - The Banting Research Fund. PMID- 20315804 TI - The Archives of Disease in Childhood. PMID- 20315805 TI - Advertisement of Cod Liver Oil. PMID- 20315806 TI - Standardization of Digitalis. PMID- 20315807 TI - The King's Evil and the Royal Touch. PMID- 20315808 TI - Doctors and the Public. PMID- 20315809 TI - Stillbirth Investigation in London, Canada, for the Year 1924: Authorized by the Child Welfare Board of the Western Ontario Academy of Medicine. PMID- 20315810 TI - An Address on Cardiac Disease. PMID- 20315811 TI - An Address on the Functions and Limits of Sport in Education. PMID- 20315812 TI - An Address on Infections of the Biliary Tract : A Stock-taking of Diagnosis and Treatment. PMID- 20315813 TI - A Simple and Accurate Method of Determining Basal Metabolic Rates : An Electrometric (Katharometer) Procedure. PMID- 20315814 TI - Neuroblastoma Occurring in Adults. PMID- 20315815 TI - The Etiology of Embryonic Deformities. PMID- 20315816 TI - A Critique of Benard's So-called Laws of the First-Born and of Alternation. PMID- 20315817 TI - Sterility Among Hybrids. PMID- 20315818 TI - Abruptio Placentae. PMID- 20315819 TI - Posterior Presentations and their Treatment. PMID- 20315820 TI - Review of Blood-Matching in Toxaemia of Pregnancy. PMID- 20315821 TI - Induction of Labour. PMID- 20315822 TI - Rectal Anaesthesia in Obstetrics. PMID- 20315823 TI - The Importance of Specific Pollens and Their Optimum Dosage for Desensitization in Hay-Fever: From an Experience of Five Years. PMID- 20315824 TI - High Blood Pressure and its Treatment by the High Frequency Current. PMID- 20315825 TI - Compound Dislocation of the Lower End of the Ulna. PMID- 20315826 TI - An Experience with Novasural. PMID- 20315827 TI - Case of Hypernephroma with Bone Metastases: History and Pathological Report. PMID- 20315829 TI - The Therapeutic Use of Oxygen. PMID- 20315828 TI - Hepatic Cirrhosis in Children with Special Reference to the Biliary Forms. PMID- 20315830 TI - Importance of Sunshine and Skyshine. PMID- 20315831 TI - The Problem of Measles. PMID- 20315833 TI - The Optical Convention at South Kensington. PMID- 20315832 TI - Investigations into the Etiology of Accidental Haemorrhage. PMID- 20315834 TI - Precautions in Tonsillectomy. PMID- 20315836 TI - The Employment of Kaolin in Intestinal Infections. PMID- 20315835 TI - Tuberculosis in North American Indians. PMID- 20315837 TI - On a Study in Vocational Guidance. PMID- 20315838 TI - The Value of Oranges in the Diet. PMID- 20315839 TI - On Birth Control. PMID- 20315840 TI - Letter from Dr. McKibben and Prof. Bruce Macallum. PMID- 20315841 TI - Letter from Dr. W. J. Macdonald. PMID- 20315842 TI - Early Acadian Hospitals. PMID- 20315843 TI - A Letter from Italy. PMID- 20315844 TI - Cheselden, Anatomist and Surgeon. PMID- 20315846 TI - An Address on the Biochemistry of Calcium. PMID- 20315845 TI - An Address on the Mental Factor in Disease and its Treatment by the General Practitioner. PMID- 20315847 TI - The Practical Application of our Present Knowledge of Calcium Metabolism. PMID- 20315848 TI - An Address on Some Forms of Anaemia. PMID- 20315849 TI - Post-Operative Pulmonary Complications: A Study from the Surgical and Gynaecological Records of the Toronto General Hospital and from the Data and Collection of the Department of Pathology of the University of Toronto. Part I. PMID- 20315850 TI - The Oral Administration of Glucose. PMID- 20315851 TI - The Relation of the Laboratory to the Practice of Medicine. PMID- 20315852 TI - Upper Respiratory Infection in its Relation to Pulmonary Disease. PMID- 20315853 TI - A Discussion of Neisser Infection in the Male. PMID- 20315854 TI - What Anaesthesia Records Show. PMID- 20315856 TI - A Survey of the Results of Routine and Other Wassermann Tests in the Toronto General Hospital for the Past Ten Years. PMID- 20315855 TI - Pyelitis in Infancy. PMID- 20315857 TI - Synergistic Analgesia in Labour. PMID- 20315859 TI - Saphenous Varix Simulating a Femoral Hernia. PMID- 20315858 TI - Bifurcate Ribs-An Unusual Cause of Deformity of the Chest. PMID- 20315860 TI - A Case of Thymoma. PMID- 20315862 TI - Recent Advances in Haematology: 3. The Blood Platelets. PMID- 20315861 TI - What is the Significance of the Spleen?: An Anatomical and Physiological Review. PMID- 20315864 TI - The Pathological Conference and the Case Method of Teaching Pathology. PMID- 20315863 TI - The Control of Diphtheria: A Review. PMID- 20315865 TI - Tobacco from a Medical Point of View. PMID- 20315866 TI - New Facts Concerning Digitalis. PMID- 20315867 TI - The Emetic Action of the Digitalis Group. PMID- 20315868 TI - Thyroxine. PMID- 20315869 TI - Sunlight. PMID- 20315870 TI - The Surgery of the Spleen. PMID- 20315871 TI - Increased Control over the Sale of Dangerous Drugs in Great Britain. PMID- 20315872 TI - The Increasing Prevalence of Encephalitis Lethargica. PMID- 20315874 TI - Raymond Pearl on Growth of Population. PMID- 20315873 TI - Prevention in Occupational Cancer. PMID- 20315875 TI - The New Foreign Members of the Royal Society. PMID- 20315876 TI - Hereditary Peroneal Atrophy. PMID- 20315877 TI - Our Edinburgh Letter. PMID- 20315879 TI - Abstracts from the Early Records of the Montreal Medico-Chirurgical Society. PMID- 20315878 TI - Our London Letter: Impulses in Sensory Nerves Produced by Normal Stimulation of Their End-Organs. PMID- 20315880 TI - The Acceleration of Growth. PMID- 20315881 TI - Auto-Experiments. PMID- 20315883 TI - Prehistoric Footprints from the Grand Canyon. PMID- 20315882 TI - American Medical Libraries. PMID- 20315884 TI - Medical Research. PMID- 20315885 TI - An Address on Addison's (Pernicious) Anaemia. PMID- 20315886 TI - Encephalitis Lethargica. PMID- 20315887 TI - Post-Operative Pulmonary Complications: A Study from the Surgical and Gynaecological Records of the Toronto General Hospital and from those of the Department of Pathology in the University of Toronto. Part II. PMID- 20315888 TI - The Problem of the Acute Ear. PMID- 20315889 TI - Malignant Growths of the Lower Urinary Tract. PMID- 20315890 TI - Cranial and Intracranial Injuries. PMID- 20315891 TI - Goitre in Children-A Study of Treatment. PMID- 20315892 TI - Thoughts on Rheumatism. PMID- 20315893 TI - Results of the Use of Scarlet Fever Antitoxin. PMID- 20315894 TI - The Relative Value of Different Tuberculin Skin Tests. PMID- 20315895 TI - Ureteral Stricture : A Cause of Obscure Abdominal and Pelvic Pain. PMID- 20315896 TI - Choice of the Anaesthetic. PMID- 20315897 TI - A Case of Hydrocephalus Simulating Brain Tumour. PMID- 20315898 TI - Banti's Disease in a Child. PMID- 20315899 TI - Recent Advances in Haematology: 4.-The Value of Splenectomy in Purpura Haemorrhagica. PMID- 20315900 TI - A Case of Symptomless Middle Meningeal Haemorrhage. PMID- 20315902 TI - The British Pharmacopoeia. PMID- 20315901 TI - The London Meeting of the Ontario Medical Association-The Swing of the Pendulum. PMID- 20315903 TI - New Knowledge of Malaria from its Use in General Paresis. PMID- 20315905 TI - The Origin of Acrodynia. PMID- 20315904 TI - Juvenile Courts. PMID- 20315907 TI - The Limitations of Cod Liver Oil in Rickets. PMID- 20315906 TI - The Eye and its Influence upon Evolution. PMID- 20315908 TI - Tuberculosis in Infancy. PMID- 20315909 TI - The Spleen in Measles. PMID- 20315910 TI - Crystalline Insulin. PMID- 20315911 TI - On Robert Burns. PMID- 20315912 TI - Verdict in Polluted Water Case. PMID- 20315913 TI - Osler Bronze Medal at University of Oxford. PMID- 20315914 TI - Fluorine Poisoning. PMID- 20315916 TI - Bird Droppings as an Infective Agent. PMID- 20315915 TI - Certificates of Health Before Marriage. PMID- 20315917 TI - Oil of Wintergreen. PMID- 20315918 TI - Juveniles and Young Persons in Penitentiaries. PMID- 20315920 TI - Research on Sleep. PMID- 20315919 TI - Maternal Mortality. PMID- 20315921 TI - Toxaemia of Burns. PMID- 20315922 TI - Activities of Rockefeller Foundation in 1925. PMID- 20315923 TI - An Historic Celebration. PMID- 20315924 TI - The Residual Effects of War Gases. PMID- 20315925 TI - Extract from Letter to Dr. M. T. Macklin. PMID- 20315926 TI - Asserted Stability of the Vitamines. PMID- 20315927 TI - Lumbar Puncture in Cases of Poisoning. PMID- 20315928 TI - A New Element. PMID- 20315929 TI - The Influence of Adrenalin on the Luminescence of Fireflies. PMID- 20315930 TI - A Hymn for Canada. PMID- 20315931 TI - An Address on Diabetes. PMID- 20315932 TI - Modern Evolution of Gynaecology. PMID- 20315933 TI - Acute Arthritis. PMID- 20315934 TI - The Low Function Kidney. PMID- 20315935 TI - Symposium on Duodenal Ulcer: 1. Medical Aspects. PMID- 20315936 TI - Symposium on Duodenal Ulcer: 2. Surgical Treatment. PMID- 20315937 TI - Symposium on Duodenal Ulcer: 3. Radiological Aspect. PMID- 20315938 TI - Nephrosis of Thyroid Origin. PMID- 20315940 TI - Allergic Diseases of Childhood. PMID- 20315939 TI - Chronic Mastitis. PMID- 20315941 TI - Newer Drugs, Their Use and Abuse. PMID- 20315942 TI - Resume on the Treatment of Fractures: Presenting the Views of the Academy of Medicine of Western Ontario. PMID- 20315943 TI - Non-Relation of Malnutrition in School Children to Infection. PMID- 20315944 TI - Expectations and Realizations from Routine Roentgenological Gastro-Intestinal Examination. PMID- 20315946 TI - Psychotherapy with Special Reference to Psychoanalysis. PMID- 20315945 TI - Carcinoma of the Prostate. PMID- 20315947 TI - A Case of Sub-Parathyroid Tetany with Collip's Extract of Parathyroid. PMID- 20315949 TI - A Case of Haemothorax in a New-Born Infant. PMID- 20315948 TI - A Case of Acute Yellow Atrophy of the Liver. PMID- 20315950 TI - Complete Heart Block: Report of a Case. PMID- 20315951 TI - A Case of Tubal Pregnancy. PMID- 20315952 TI - Impacted Tooth with Infection. PMID- 20315953 TI - The Prince of Wales and the Value of Science. PMID- 20315954 TI - Impressions of a Free Lance at the Nottingham Meeting. PMID- 20315955 TI - The Centenary of Lister. PMID- 20315956 TI - What's What? PMID- 20315957 TI - On the Track of a Fallacy. The Guanidine Theory. PMID- 20315958 TI - Inheritance in Cancer: A Note on the Work of Maud Slye. PMID- 20315959 TI - The Psychogenetic Element in Epilepsy. PMID- 20315960 TI - On Menstruation and Pain. PMID- 20315961 TI - A Definition of Blindness. PMID- 20315962 TI - On the Relation of Dose and Effect in Therapeutics. PMID- 20315963 TI - Meeting of the Interstate Post-Graduate Assembly of North America, Cleveland. PMID- 20315964 TI - Tuberculin in Crystalline Form. PMID- 20315965 TI - Care of the Feeble Minded in England. PMID- 20315966 TI - New Views on Plant Life. PMID- 20315967 TI - The Nova Scotia Temperance Act and the Profession. PMID- 20315968 TI - Vegetable as Opposed to Animal Fats. PMID- 20315969 TI - Congress of Physicians Speaking the French Language in North America. PMID- 20315970 TI - On the Opening of a Post-Graduate Hostel in London. PMID- 20315971 TI - Our London Letter. PMID- 20315973 TI - The Training of Nurses. PMID- 20315972 TI - Our Edinburgh Letter. PMID- 20315974 TI - Is Discussion of Paper read at a Meeting Desirable? PMID- 20315975 TI - The Art of Writing Medical Papers. PMID- 20315976 TI - Cambridge Medical Worthies. PMID- 20315977 TI - The Character of Claudius. PMID- 20315978 TI - Cretins-An Etymological Note. PMID- 20315979 TI - Cremation. PMID- 20315980 TI - An Address on the Abdominal Emergency. PMID- 20315981 TI - On Certain Grooves upon the Deep Aspect of the Cranial Vault. PMID- 20315982 TI - Physical Examination and Determination of Basal Metabolic Rates of a Group of Young Adults. PMID- 20315983 TI - The Treatment of Laryngeal Tuberculosis in Sanatoria. PMID- 20315984 TI - The Value of Parallel Kolmer and Kahn Tests as a Standardized laboratory Procedure in the Serum Diagnosis of Syphilis. PMID- 20315985 TI - The Importance of Tubercle Bacillus in the Etiology of Ischio-Rectal Abscess and Fistula in Ano. PMID- 20315986 TI - A Case Of Haemolytic Jaundice in the Newborn. PMID- 20315987 TI - Abdominal Pain in Children in Extra-Abdominal Conditions. PMID- 20315988 TI - Breech Extraction as a Cause of Cord Laceration and Paraplegia. PMID- 20315989 TI - Diagnosis of Common Skin Conditions. PMID- 20315990 TI - The Infective Arthritides: On a Possible Relationship Between Hypoparathyroidism and the Chronic Arthritides. PMID- 20315991 TI - Social Aspects of Mental Deficiency. PMID- 20315992 TI - An Effective Medical Treatment for the Cure of Chronic Gastric and Duodenal Ulcers. PMID- 20315993 TI - Evolution of Man's Diet. PMID- 20315994 TI - A Case of a Needle in the Cervical Region Tolerated for Five Months. PMID- 20315995 TI - A Late Report on a Case of Functional Albuminuria. PMID- 20315996 TI - Lymphoblastoma. PMID- 20315997 TI - Rheumatic Infection in Children. PMID- 20315998 TI - On Wealth, Philanthropy, and Mental Hygiene. PMID- 20315999 TI - The Sanatorium and the Student. PMID- 20316000 TI - The Epilepsies. PMID- 20316001 TI - Crime and Its Abatement. PMID- 20316002 TI - Mechanism of Pancreatic Secretion. PMID- 20316003 TI - On The Value of the Sanatorium Treatment in Tuberculosis. PMID- 20316004 TI - Encephalo-Myelitis Following Vaccination. PMID- 20316006 TI - Liver Extract in the Treatment of Malignant Disease. PMID- 20316005 TI - On Diet and Nutrition. PMID- 20316007 TI - Public Education in Health. PMID- 20316008 TI - Our London Letter. PMID- 20316009 TI - The Twelfth International Congress of Physiologists. PMID- 20316010 TI - The Story of Diphtheria. PMID- 20316011 TI - The Madness of Ajax Clinically Considered. PMID- 20316012 TI - Mediaeval Medicine. PMID- 20316013 TI - The Induction of Aborption its Indications. PMID- 20316014 TI - Extramural Post-Graduate Course. PMID- 20316015 TI - Structure of Neurone Junctions. PMID- 20316016 TI - A Doctor's Signboard. PMID- 20316017 TI - ERRATA. PMID- 20316018 TI - An Address on the University's function in Medicine. PMID- 20316019 TI - An Address on Some Contributions to our Knowledge of Diseases of the Kidney and Liver : Part I. PMID- 20316021 TI - An Address on Fibrositis (Myalgia, Chronic Muscular Rheumatism). PMID- 20316020 TI - An Address on Headaches, with Especial Reference to Those of Ocular Origin. PMID- 20316022 TI - An Address on Occupational Therapy. PMID- 20316023 TI - The Practice of Medicine : Abstract of Inaugural Address of the President of the Academy of Medicine. PMID- 20316024 TI - Pre-Operative and Post-Operative Principles. PMID- 20316025 TI - Indications for Use of Extra-Pleural Thoracoplasty. PMID- 20316026 TI - An Improved Mode of Expression of Haemoglobin Values. PMID- 20316027 TI - Hereditary Abnormalities of the Eye: I. Introduction: The Laws of Heredity and Their Exemplification in the Inheritance of Eye Colour. PMID- 20316028 TI - Diuresis and the Newer Diuretics-Ammonium Chloride and Novasurol. PMID- 20316029 TI - The Diuretic action of Ammonium Chloride and Novasurol. PMID- 20316030 TI - Types of Thrombopenic purpura Haemorrhagica. PMID- 20316031 TI - Radium in Dermatology. PMID- 20316032 TI - Prostatism: A Brief Survey of One Hundred Cases. PMID- 20316033 TI - The Treatment of Haemorrhoids. PMID- 20316034 TI - Meningo-Encephalitis; Operation; Recovery. PMID- 20316035 TI - A Case of Amaurotic Family Idiocy. PMID- 20316037 TI - The Care of the Sick and the Prevention of Disease. PMID- 20316036 TI - On Spastic Paralysis and Its Treatment. PMID- 20316038 TI - Inherited Blindness. PMID- 20316040 TI - The War on Disease: Sir George Newman's Report for 1925. PMID- 20316039 TI - Professor Finsterer and Anaesthesia in Abdominal Surgery. PMID- 20316041 TI - Some Aspects of Pain. PMID- 20316042 TI - The Menace of Obesity. PMID- 20316044 TI - On the Value of Tryparsamide, in the Treatment of the Later Symptoms of Syphilis. PMID- 20316043 TI - The Treatment of Psoriasis. PMID- 20316046 TI - The Seymour Plan for Elimination of Diphtheria, Smallpox and Typhoid. PMID- 20316045 TI - The Present Position of Sanocrysin. PMID- 20316047 TI - Publicity in Medicine. PMID- 20316048 TI - On Rheumatic Disease in Children. PMID- 20316049 TI - The Gye-Barnard Organism of Cancer. PMID- 20316050 TI - The influence of Climate in the production of Catarrhal Colds. PMID- 20316051 TI - Our Edinburgh Letter. PMID- 20316053 TI - When Not to Operate for Hernia. PMID- 20316052 TI - Our London Letter. PMID- 20316054 TI - Common Sense in Medicine. PMID- 20316055 TI - Diet for School-boys. PMID- 20316056 TI - The Nervous System of Plants. PMID- 20316058 TI - Goggles for Ultra-Violet Therapy. PMID- 20316057 TI - On Benzol Poisoning as an Industrial Hazard. PMID- 20316059 TI - A New Drug for Treatment of Malaria. PMID- 20316060 TI - Ability of Different Racial Types. PMID- 20316061 TI - A New Ultra-Violet Transmitting Glass. PMID- 20316062 TI - The French Guinea Station of the Pasteur Institute. PMID- 20316063 TI - The Alcohol Content of Bread. PMID- 20316064 TI - An Address on the Prevention, Diagnosis and Treatment of Post-operative Peritonitis. PMID- 20316065 TI - An Address on the Present Status of Serum Therapy in the Treatment of the Exanthemata. PMID- 20316066 TI - An Address on the Psychogenic Psychoses: Their Causes and Symptoms. PMID- 20316067 TI - Some Contributions to our Knowledge of Diseases of the Kidney and Liver : Part II. PMID- 20316068 TI - Iodized Oil with Reference to Bronchiectasis. PMID- 20316069 TI - Haemolytic Influenza Bacilli in Acute Respiratory Infection. PMID- 20316070 TI - Paroxysmal Tachycardia. PMID- 20316071 TI - The Present Status of Cholecystography. PMID- 20316073 TI - Acute Cranial-Cerebral Injuries. PMID- 20316072 TI - Leptospirosis Icterohaemorrhagica (Weil's Disease) with Report of a Fatal Case. PMID- 20316074 TI - On Pathological Conditions in the Upper Respiratory Tract, and the Importance of their Recognition and Correction in Chest Disabilities. PMID- 20316075 TI - On Some of the Less Common Early Signs of Disseminated Sclerosis with the Report of Some Cases. PMID- 20316076 TI - Bladder Dysfunction Secondary to Nerve Lesions. PMID- 20316077 TI - The Mortality in Appendicitis. PMID- 20316078 TI - The Potency of Tinctures of Digitalis and Strophanthus: A Discussion. PMID- 20316079 TI - The Value of Organized Supervision in the Care of Children as Exemplified by Results at the Infants' Home, Toronto. PMID- 20316080 TI - Acute Lymphatic Leukaemia. PMID- 20316081 TI - Severe Renal Trauma with Rupture of Renal Artery; Absence of Haematuria. PMID- 20316082 TI - Infected Hand Followed by Loss of Power in the Extensors of Fingers and Thumbs. PMID- 20316084 TI - The Modern Surgeon. PMID- 20316083 TI - Myocardial Insufficiency, Its Prevention and Treatment. PMID- 20316085 TI - The Prognosis of Angina Pectoris. PMID- 20316086 TI - Posture. PMID- 20316087 TI - The Care of the Sick : Means of diagnosis: How can they be made more generally available? PMID- 20316089 TI - On the Hospitals of Canada. PMID- 20316088 TI - International Sanitary Interests. PMID- 20316091 TI - Emotional Reactions in Disseminated Sclerosis. PMID- 20316090 TI - Colour-Blindness. PMID- 20316092 TI - Sir James Mackenzie. PMID- 20316094 TI - The Value of Malarial Therapy in Dementia Paralytica. PMID- 20316093 TI - A Crystalline Ferment. PMID- 20316095 TI - Poliomyelitis and Polio-Encephalitis. PMID- 20316096 TI - Anti-Malarial Measures. PMID- 20316097 TI - Prohibition's Failure in Norway. PMID- 20316098 TI - Vaccination Before Jenner. PMID- 20316099 TI - On Symposia. PMID- 20316100 TI - Alcoholism in America. PMID- 20316101 TI - On The Debt of Medicine to the Experimental Methods of Harvey. PMID- 20316102 TI - London Letter. PMID- 20316103 TI - Edinburgh Letter. PMID- 20316104 TI - The Re-Opening of the Wellcome Museum of Medical History. PMID- 20316105 TI - Electrotherapy in Surgery. PMID- 20316106 TI - Caleb Hillier Parry and Something of His Contemporaries. PMID- 20316107 TI - Be on Your Guard. PMID- 20316108 TI - Foreword 1927. PMID- 20316109 TI - Hyperglycaemia in Paralysis Agitans. PMID- 20316110 TI - A DISSERTATION ON DISCONTENT. PMID- 20316111 TI - THE DIFFICULTIES OF RESEARCH. PMID- 20316112 TI - THE BASAL METABOLISM AFTER THE ARTIFICIAL MENOPAUSE. PMID- 20316113 TI - SPERMINE. PMID- 20316114 TI - EPIDEMIC POLIOMYELITIS IN ENGLAND. PMID- 20316115 TI - ON AUTOMOBILE ACCIDENTS. PMID- 20316116 TI - ON MEDICAL WRITING. PMID- 20316117 TI - SEQUELAE OF ENCEPHALITIS LETH-ARGICA IN CHILDREN. PMID- 20316118 TI - An Address ON THE IMMEDIATE AND ULTIMATE PROGNOSIS IN CARDIAC DISEASE. PMID- 20316120 TI - SOME FACTS ABOUT THE CANADIAN MEDICAL ASSOCIATION. PMID- 20316119 TI - Our London Letter. PMID- 20316122 TI - Two Factors in Catarrhal Deafness. PMID- 20316121 TI - THE LISTER MEMORIAL COMMITTEE HAS APPROVED THE FOLLOWING LETTER TO MEDICAL SCHOOLS AND HOSPITALS. PMID- 20316123 TI - REPORT OF THE COMMITTEE ON PERSONAL ARCHIVES. PMID- 20316125 TI - Silent Pulmonary Cavities. PMID- 20316124 TI - An Address ON THE PRESENT POSITION OF THE CANCER PROBLEM. PMID- 20316126 TI - An Address ON THE PRE-OPERATIVE PREPARATION OF THE DIABETIC PATIENT WITH DISCUSSION OF THE "SO-CALLED" DIABETIC GANGRENE. PMID- 20316127 TI - Tailed Children. PMID- 20316128 TI - An Address ON DIABETIC GANGRENE. PMID- 20316129 TI - An Address ON PUERPERAL INFECTION. PMID- 20316130 TI - Importation of Useful Parasites. PMID- 20316131 TI - THE PHYSIOLOGICAL FACTORS DETERMINING THE ACIDITY OF THE GASTRIC JUICE AND OF THE GASTRIC CONTENTS. PMID- 20316132 TI - Bacterium Pneumosintes and Influenza. PMID- 20316133 TI - THE CARBON MONOXIDE MENACE AND THE CANCER PROBLEM. PMID- 20316134 TI - ACUTE GANGRENOUS CHOLECYSTITIS. PMID- 20316136 TI - The Rheumatic Child. PMID- 20316135 TI - ON TERMINAL DISINFECTION. PMID- 20316137 TI - HEREDITARY ABNORMALITIES OF THE EYE: II. INHERITABLE DEFECTS INVOLVING THE EYELIDS AND THEIR MODE OF TRANSMISSION. PMID- 20316139 TI - OSTEITIS DEFORMANS (PAGET'S DISEASE). PMID- 20316138 TI - Epidemic Meningitis. PMID- 20316140 TI - A NOTE CONCERNING THE RADIOGRAPHIC DIFFERENTIATION BETWEEN DIPLOIC AND MENINGEAL VASCULAR CHANNELS. PMID- 20316142 TI - Exhibition at the Science Museum at South Kensington. PMID- 20316141 TI - HEREDITARY HAEMORRHAGIC TELANGIECTASIA. PMID- 20316143 TI - RINGWORM OF THE HANDS AND FEET. PMID- 20316144 TI - An Address ON THE TOXAEMIAS OF PREGNANCY. PMID- 20316145 TI - SOME PITFALLS IN THE DIAGNOSIS OF INTUSSUSCEPTION. PMID- 20316146 TI - ON THE USE OF IRON IN ANAEMIA. PMID- 20316148 TI - Preliminary Report of Committee on Education Approved by Council on Physical Therapy of American Medical Association. PMID- 20316147 TI - CLEFT PALATE: A CLINICAL STUDY OF A METHOD FOR ITS TREATMENT. PMID- 20316149 TI - A CASE OF PERFORATED PEPTIC ULCER OF MECKEL'S DIVERTICULUM. PMID- 20316151 TI - DERMATITIS VEGETANS (REPORT OF A CASE). PMID- 20316150 TI - SPINDLE CELL SARCOMA OF THE PROSTATE. PMID- 20316152 TI - FRACTURE OF THE SKULL IN A CHILD SIX MONTHS OF AGE. PMID- 20316153 TI - TANNIC ACID TREATMENT OF BURNS. PMID- 20316154 TI - DIABETES MELLITUS AND MYXOEDEMA. PMID- 20316156 TI - A CASE OF ENCYSTED SHRAPNEL. PMID- 20316155 TI - PERSISTENT THYMUS. PMID- 20316157 TI - THE RELATIVE VALUE OF THE ROENTGEN RAY AND OF PHYSICAL FINDINGS IN THE DIAGNOSIS OF PULMONARY TUBERCULOSIS. PMID- 20316159 TI - Influence of Insulin on Mortality from Diabetes. PMID- 20316158 TI - NEW DEVELOPMENTS IN OUR KNOWLEDGE OF THE GALL BLADDER. PMID- 20316160 TI - THE CARE OF THE SICK: TREATMENT, AND HOSPITALIZATION, AND PAYMENT THEREFOR. PMID- 20316161 TI - THE CANADIAN NATIONAL COMMITTEE FOR MENTAL HYGIENE. PMID- 20316162 TI - THE CANADIAN COUNCIL ON CHILD WELFARE. PMID- 20316163 TI - An Address ON EMPYEMA. PMID- 20316164 TI - An Address ON THE RELATIONS OF THE MEDICAL PROFESSION TO HOSPITALS. PMID- 20316165 TI - Merbaphen (Novasurol) as Diuretic in Congestive Heart Failure. PMID- 20316166 TI - An Address ON THE PRESENT POSITION OF THE CANCER PROBLEM. PMID- 20316167 TI - An Address ON THE GROWTH OF THE SPECIALTY OF ANAESTHESIA IN CANADA. PMID- 20316168 TI - An Address ON PROGNOSIS. PMID- 20316169 TI - THE CHOLESTEROL CONTENT OF THE BLOOD PLASMA AS AN INDEX OF PROGRESS IN INSULIN TREATED DIABETICS. PMID- 20316170 TI - THE TREATMENT OF DIABETES MELLITUS THROUGH OFFICE PRACTICE. PMID- 20316172 TI - THE SIGNIFICANCE OF GENITO-URINARY PAIN. PMID- 20316171 TI - THE RELATION OF KIDNEY ACTIVITY IN DIABETES INSIPIDUS TO THE THEORIES OF URINE EXCRETION. PMID- 20316173 TI - AN ANALYSIS OF 150 DEATHS FROM DIPHTHERIA. PMID- 20316174 TI - THE TREATMENT AND CAUSES OF CONVULSIONS IN INFANTS AND CHILDREN. PMID- 20316175 TI - DIABETIC LIPAEMIA RETINALIS: WITH REPORT OF A CASE. PMID- 20316177 TI - SEX FACTORS IN THE VERY YOUNG CHILD. PMID- 20316176 TI - A CASE OF PLACENTA ACCRETA. PMID- 20316178 TI - Effects of Diet During Pregnancy on Development of Rickets in Offspring. PMID- 20316179 TI - New Instruments and Technique: ELECTRO-COAGULATION AS AN ADJUNCT IN TONSIL DISSECTIONS. PMID- 20316180 TI - HEREDITARY DIABETES INSIPIDUS. PMID- 20316181 TI - DIABETES IN A CHILD THREE YEARS OF AGE. PMID- 20316182 TI - LUNG STONES (PNEUMOLITHS) POSSIBLY ASSOCIATED WITH TUBERCULOSIS. PMID- 20316183 TI - CASE OF HYPSILOID (DICEPHALUS MONOSOMUS). PMID- 20316184 TI - A DICEPHALOUS FOETUS. PMID- 20316185 TI - DELIVERY OF SYNCEPHALUS THORACOPAGUS. PMID- 20316186 TI - ECHINOCOCCUS CYST OF THE OMENTUM. PMID- 20316187 TI - Experimental Investigations on Convulsions. PMID- 20316188 TI - SOME FUNCTIONS OF THE SPLEEN. PMID- 20316189 TI - ON HEADACHES. PMID- 20316190 TI - THE MAZE OF MEDICINE. PMID- 20316191 TI - THE MANAGEMENT OF HOSPITALS. PMID- 20316192 TI - CONCERNING ANATOMY. PMID- 20316193 TI - THE HISTORY OF CANADIAN MEDICINE. PMID- 20316195 TI - RACIAL CHARACTERS OF THE SKIN IN RELATION TO HEALTH. PMID- 20316194 TI - ON THE CONSERVATION OF HEARING IN SCHOOL CHILDREN. PMID- 20316196 TI - THE DEVELOPMENT OF OBSTETRICS. PMID- 20316197 TI - THE EARLY RECOGNITION OF COMMENCING MYOCARDIAL WEAKNESS. PMID- 20316198 TI - VALUE OF IRON AS A THERAPEUTIC AGENT. PMID- 20316199 TI - ON THE AFTER EFFECTS OF POISON GAS. PMID- 20316200 TI - A VACCINATION ENQUIRY. PMID- 20316202 TI - THE SECOND IMPRESSION OF THE SIR WILLIAM OSLER MEMORIAL VOLUME. PMID- 20316201 TI - PELLAGRA. PMID- 20316203 TI - Our London Letter. PMID- 20316204 TI - A CANADIAN DR. MACLURE. PMID- 20316205 TI - REGARDING TRANSFUSION AND INTRAVENOUS INJECTIONS. PMID- 20316206 TI - MERCUROCHROME. PMID- 20316207 TI - HYDRATED MORPHINE DERIVATIVES. PMID- 20316208 TI - THE ORIGIN OF SYPHILIS. PMID- 20316209 TI - Thyroid Hypertrophy and Pregnancy. PMID- 20316210 TI - THE REBUILDING OF "BARTS" IN THE EIGHTEENTH CENTURY. PMID- 20316211 TI - An Address ON METABOLIC FACTORS IN THE TREATMENT OF TUBERCULOSIS. PMID- 20316212 TI - An Address ON THE FUNCTIONS OF A WOMAN'S CLINIC. PMID- 20316213 TI - An Address ON PAIN IN THE LOWER ABDOMEN. PMID- 20316214 TI - An Address ON THE APPENDIX PROBLEM TO-DAY. PMID- 20316215 TI - An Address ON FOCAL INFECTION IN RELATION TO SYSTEMIC DISEASE. PMID- 20316216 TI - EXTRA-UTERINE PREGNANCY. PMID- 20316217 TI - MULTIPLE MYELOMA OF UNUSUAL TYPE WITH WIDELY DISSEMINATED METASTASES OF SMALL SIZE. PMID- 20316218 TI - Pollen Toxaemia in Children. PMID- 20316219 TI - THE ANAEMIA OF CANCER OF THE GASTRO-INTESTINAL TRACT: BASED ON A STUDY OF 187 CASES. PMID- 20316220 TI - THE MEIOSTAGMIN REACTION IN THE DIAGNOSIS OF CARCINOMA. PMID- 20316221 TI - REMARKS ON THE DEEP MUSCLES OF THE BACK, WITH REFERENCE TO INFANTILE PARALYSIS. PMID- 20316223 TI - Investigation of Injuries from Hair Dyes, Dyed Furs and Cosmetics. PMID- 20316222 TI - NOVA SCOTIA'S CHANGING STATISTICS. PMID- 20316224 TI - A CASE OF MALIGNANCY IN A DERMOID CYST OF THE OVARY. PMID- 20316225 TI - SOME OBSERVATIONS ON "SADDLE-NOSE" DEFORMITY IN CHILDREN. PMID- 20316226 TI - HEREDITARY ABNORMALITIES OF THE EYE III. (SECTION 1) ANOMALIES OF THE ENTIRE EYEBALL. PMID- 20316227 TI - THE TREATMENT OF EARLY MALIGNANCY OF THE LARYNX BY ELECTRO-DESICCATION AND RADIUM. PMID- 20316228 TI - REPORT OF A CASE OF HYDROPS NEONATORUM. PMID- 20316229 TI - REPORTS OF THREE CASES OF INJURY TO THE RIGHT KNEE. PMID- 20316230 TI - GENERALIZED NON-TRAUMATIC SUBCUTANEOUS EMPHYSEMA: WITH REPORT OF A CASE IN A YOUNG CHILD. PMID- 20316231 TI - Toxaemias of Pregnancy and Treatment of Eclampsia. PMID- 20316232 TI - Use of Radium in Internal Medicine. PMID- 20316234 TI - ON RACIAL DECADENCE. PMID- 20316233 TI - THE CLINICAL STUDY OF MENTAL DISORDERS. PMID- 20316235 TI - ON RESUSCITATION AFTER SYSTEMIC DEATH. PMID- 20316236 TI - ON GOITRE. PMID- 20316237 TI - THE MEDICAL PROFESSION FROM AN INTERNATIONAL VIEWPOINT. PMID- 20316238 TI - PARA-THOR-MONE. PMID- 20316239 TI - INFANT MORTALITY. PMID- 20316240 TI - CYCLIC VOMITING AND MIGRAINE. PMID- 20316241 TI - HIGH BLOOD PRESSURE. PMID- 20316242 TI - OUR IMMIGRATION LAWS. PMID- 20316243 TI - A SURVEY OF TUBERCULOSIS AMONG INDIANS IN THE QU'APPELLE VALLEY. PMID- 20316244 TI - MALARIAL TREATMENT OF GENERAL PARALYSIS.